The DOI matches its Crossref record; 219 of the 219 references it cites were found in a registry or an index; 15 of the 331 sources its claims cite were checked for support.
Osteosarcoma
Open accessAbstract
Osteosarcoma is the most common primary malignant tumour of the bone. Osteosarcoma incidence is bimodal, peaking at 18 and 60 years of age, and is slightly more common in males. The key pathophysiological mechanism involves several possible genetic drivers of disease linked to bone formation, causing malignant progression and metastasis. While there have been significant improvements in the outcome of patients with localized disease, with event-free survival outcomes exceeding 60%, in patients with metastatic disease, event-free survival outcomes remain poor at less than 30%. The suspicion of osteosarcoma based on radiographs still requires pathological evaluation of a bone biopsy specimen for definitive diagnosis and CT imaging of the chest should be performed to identify lung nodules. So far, population-based screening and surveillance strategies have not been implemented due to the rarity of osteosarcoma and the lack of reliable markers. Current screening focuses only on groups at high risk such as patients with genetic cancer predisposition syndromes. Management of osteosarcoma requires a multidisciplinary team of paediatric and medical oncologists, orthopaedic and general surgeons, pathologists, radiologists and specialist nurses. Survivors of osteosarcoma require specialized medical follow-up, as curative treatment consisting of chemotherapy and surgery has long-term adverse effects, which also affect the quality of life of patients. The development of osteosarcoma model systems and related research as well as the evaluation of new treatment approaches are ongoing to improve disease outcomes, especially for patients with metastases. Osteosarcoma is the most common primary malignant tumour of the bone. This Primer by Gorlick and colleagues summarizes the epidemiology, mechanisms, diagnosis and treatment of this disorder as well as the quality of life of patients and open research questions.
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Claims the paper makes
199 Not checked yet · 49 No basis given · 10 Own interpretation · 6 Partly supported · 2 Supported · 1 Own method · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Of note, the resulting complex genomes are subsequently maintained with some fidelity, even from diagnosis to relapse 35,37 .”
§ Osteosarcoma > Chromosomal complexity and copy number alterations
What the sources say
- Partly supportedcites [35] Sayles, L. C. et al. Genome-informed targeted therapy for osteosarcoma. Cancer Discov. 9, 46–63 (2019). A study that defines potentially actionable molecular subtypes of osteosarcoma. sourceExperimental — accuracy not yet measured
The Results section reports that osteosarcoma genomes are highly complex and that whole-genome copy-number profiles were largely consistent between samples from the same patient. It includes diagnostic biopsies and metastases, but does not explicitly establish that the consistent profiles were from paired diagnosis-to-relapse samples; the stability finding concerns copy-number alterations rather than every genomic feature. No page number is available in our copy. (LLM, conf=0.82)
- Supportedcites [37] Rajan, S. et al. Remarkably stable copy-number profiles in osteosarcoma revealed using single-cell DNA sequencing. Preprint at bioRxiv https://doi.org/10.1101/2021.08.30.458268 (2021). source
The Abstract reports that, despite extensive structural complexity, osteosarcoma tumors showed little subclonal diversification and that SCNA profiles were conserved from diagnosis to relapse. The 'Complex but Stable Copy-number Profiles in Osteosarcoma' section likewise reports relatively stable profiles across those timepoints. The finding concerns copy-number structure, not every type of genomic alteration. (LLM, conf=0.92)
plain- Asserted: passes — The authors put it forward as true.
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- Partly supported
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In the paper
“Preclinical data evaluating antibody-drug conjugates, such as those targeting B7H3 (ref.90 ), LRRC15 (ref.86 ) and HER2 (ref.91 ), have been particularly promising and are rapidly moving to and through clinical trials.”
§ Osteosarcoma > Immune approaches
What the sources say
- Partly supportedcites [90] Kendsersky, N. M. et al. The B7-H3–targeting antibody–drug conjugate m276-SL-PBD is potently effective against pediatric cancer preclinical solid tumor models. Clin. Cancer Res. 27, 2938–2946 (2021). sourceExperimental — accuracy not yet measured
The Results (page unavailable) report complete or maintained complete responses in four of five osteosarcoma models treated with the B7-H3-targeting ADC, supporting the promising preclinical-data claim. The Discussion says B7-H3 ADCs could be developed clinically, but does not say they are rapidly moving to or through clinical trials. The citation is attached to B7-H3, not the separate LRRC15 and HER2 examples. (LLM, conf=0.88)
- Supportedcites [86] Hingorani, P. et al. ABBV-085, antibody–drug conjugate targeting LRRC15, is effective in osteosarcoma: a report by the pediatric preclinical testing consortium. Mol. Cancer Ther. 20, 535–540 (2021). source
The citation is attached specifically to LRRC15, not B7H3 or HER2. The Discussion reports significant antitumor activity of the LRRC15-targeting conjugate ABBV-085 in osteosarcoma models and says it had entered clinical testing, with responses observed in patients with osteosarcoma. (LLM, conf=0.91)
- Not checked yetcites [91] Hingorani, P. et al. Abstract LB-217: Preclinical evaluation of trastuzumab deruxtecan (T-DXd; DS-8201a), a HER2 antibody-drug conjugate, in pediatric solid tumors by the Pediatric Preclinical Testing Consortium (PPTC).Cancer Res. 80 (Suppl. 16), LB-217 (2020). source
boosted- Asserted: passes — The authors put it forward as true.
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- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The emerging preclinical data for chimeric antigen receptor (CAR) T and CAR natural killer cell therapies are encouraging 88,89 ,”
§ Osteosarcoma > Immune approaches
What the sources say
- Partly supportedcites [88] Lange, S. et al. A chimeric GM-CSF/IL18 receptor to sustain CAR T-cell function. Cancer Discov. 11, 1661–1671 (2021). sourceExperimental — accuracy not yet measured
The Results section reports encouraging preclinical findings for GM18-modified HER2-CAR T cells in an osteosarcoma mouse model, including a significant survival advantage. The cited paper does not provide evidence for CAR natural killer cell therapy, so it supports only the CAR T-cell part of the sentence. No page number is available in our copy. (LLM, conf=0.88)
- Not checked yetcites [89] Tullius, B. P., Setty, B. A. & Lee, D. A. In Current Advances in Osteosarcoma: Clinical Perspectives: Past, Present and Future (eds Kleinerman, E. S. & Gorlick, R.) 141–154 (Springer International Publishing, 2020). source
plain- Asserted: passes — The authors put it forward as true.
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- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Indeed, clinical responses to ICIs have been generally disappointing 84,85 ,”
§ Osteosarcoma > Immune approaches
What the sources say
- Supportedcites [84] Tawbi, H. A. et al. Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol. 18, 1493–1501 (2017). source
The Results report one confirmed response among 22 osteosarcoma patients treated with pembrolizumab, an immune-checkpoint inhibitor. The Discussion describes pembrolizumab’s activity in bone sarcomas as limited and notes that only one patient with metastatic osteosarcoma responded. The paper supports the cited statement as an example of disappointing clinical responses, though this trial tested pembrolizumab rather than all ICIs. (LLM, conf=0.90)
- Supportedcites [85] Le Cesne, A. et al. Programmed cell death 1 (PD-1) targeting in patients with advanced osteosarcomas: results from the PEMBROSARC study. Eur. J. Cancer 119, 151–157 (2019). source
The Discussion (page not provided) reports significant clinical benefit in only 2 of 15 patients in PEMBROSARC and a partial response in only 1 of 22 osteosarcoma patients in SARC028. It characterizes PD-1 inhibition as having only modest activity in advanced osteosarcoma, supporting the cited generalization. (LLM, conf=0.91)
plain- Asserted: passes — The authors put it forward as true.
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- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Among all paediatric patients with cancer, those with osteosarcoma carry one of the highest rates of genetic cancer predisposition (10-20%) 12 ; Li-Fraumeni syndrome is the most prominent but hereditary retinoblastoma, helicase-associated cancers and others also contribute 157 .”
§ Osteosarcoma > Late effects
What the sources say
- Supportedcites [12] Mirabello, L. et al. Frequency of pathogenic germline variants in cancer-susceptibility genes in patients with osteosarcoma. JAMA Oncol. 6, 724–734 (2020). This study demonstrates a high frequency of potentially pathogenic germline mutations in patients with osteosarcoma, supporting the role of germline genetic testing. source
The Discussion reports that 18.4% of patients with osteosarcoma had a pathogenic or likely pathogenic variant in an autosomal-dominant cancer-susceptibility gene and says this frequency was higher than previously reported for any other pediatric cancer. That supports the cited sentence’s 10–20% range and its comparative claim. The paper separately reports 28.0% when variants across all cancer-susceptibility genes are counted. (LLM, conf=0.88)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Supported
In the paper
“Patients who were and were not randomized to such salvage therapy had event-free survival rates of 53% (95% CI 47-53%) and 55% (95% CI 49-60%), respectively.”
§ Osteosarcoma > Systemic therapy at diagnosis
What the sources say
- Not checked yetcites [114] Marina, N. M. et al. Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial. Lancet Oncol. 17, 1396–1408 (2016). An international randomized clinical trial fails to show benefit of addition of I/E to MAP chemotherapy in the primary treatment of osteosarcoma. source
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“A growing number of cancer predisposition syndromes are considered risk factors for the development of osteosarcoma, including Li-Fraumeni syndrome, hereditary retinoblastoma and Diamond-Blackfan anaemia as well as primary DNA helicase disorders involving the RECQ family of genes, including Rothmund-Thomson syndrome, RAPADILINO syndrome, Bloom syndrome and Werner syndrome 19,20,21”
§ Osteosarcoma > Genetic predisposition
What the sources say
- Not checked yetcites [19] Vlachos, A., Rosenberg, P. S., Atsidaftos, E., Alter, B. P. & Lipton, J. M. Incidence of neoplasia in Diamond Blackfan anemia: a report from the Diamond Blackfan Anemia Registry. Blood 119, 3815–3819 (2012). source
- Not checked yetcites [20] Wang, L. L. et al. Association between osteosarcoma and deleterious mutations in the RECQL4 gene in Rothmund-Thomson syndrome. J. Natl Cancer Inst. 95, 669–674 (2003). source
- Not checked yetcites [21] Lu, L., Jin, W. & Wang, L. L. RECQ DNA helicases and osteosarcoma. Adv. Exp. Med. Biol. 1258, 37–54 (2020). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Those patients with radiographically confirmed non-metastatic osteosarcoma have a 5-year event-free survival of ~60% 9 .”
§ Osteosarcoma > Epidemiology Incidence and mortality
What the sources say
- Not checked yetcites [9] Gill, J. & Gorlick, R. Advancing therapy for osteosarcoma. Nat. Rev. Clin. Oncol. 18, 609–624 (2021). source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Osteosarcoma in adults (age >40 years) and elderly populations (age >60 years) tends to occur secondary to other conditions, such as Paget disease of bone, as transformation of other benign bone conditions or as a late effect of therapeutic irradiation 14 .”
§ Osteosarcoma > Influence of age and sex
What the sources say
- Not checked yetcites [14] Czerniak, B. Dorfman and Czerniak’s Bone Tumors E-Book (Elsevier Health Sciences, 2015).
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Similarly, exposure to alkylating chemotherapy, particularly when given along with radiotherapy, has been associated with an increased incidence of subsequent osteosarcoma in childhood cancer survivors 25 .”
§ Osteosarcoma > Radiation and chemotherapy
What the sources say
- Not checked yetcites [25] Tucker, M. A. et al. Bone sarcomas linked to radiotherapy and chemotherapy in children. N. Engl. J. Med. 317, 588–593 (1987). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- It may state two separate claims as one. 107
- Probably not a substantial claim. 50
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The single most frequently altered gene is the tumour suppressor TP53, which is lost in >90% of osteosarcoma tumours, with the majority lost through intron 1 rearrangements or deletions rather than through point mutations 33,36,38 .”
§ Osteosarcoma > Recurrent mutations
What the sources say
- Partly supportedcites [33] Chen, X. et al. Recurrent somatic structural variations contribute to tumorigenesis in pediatric osteosarcoma. Cell Rep. 7, 104–112 (2014). The majority of TP53 loss in osteosarcoma occurs through intron 1 rearrangements or deletions rather than through point mutations. sourceExperimental — accuracy not yet measured
The Discussion (Genomic Stability and Osteosarcoma Initiation and Progression) calls TP53 the most frequently mutated gene and says most TP53 mutations are structural variations in intron 1. It estimates that at least one TP53 allele is mutated in more than 90% of tumors **in the discovery cohort**; the claim omits that limitation and presents the figure as applying to osteosarcoma tumors generally. (LLM, conf=0.86)
- Partly supportedcites [36] Wu, C. C. et al. Immuno-genomic landscape of osteosarcoma. Nat. Commun. 11, 1008 (2020). Molecular profiling of samples from patients with osteosarcoma characterizes immune subsets, including immune enrichment among older patients. sourceExperimental — accuracy not yet measured
The Results (Genomic landscape; page unavailable) report TP53 aberrations and losses of heterozygosity involving TP53 and/or RB1, and the Discussion describes TP53 loss in osteosarcoma. Our copy does not establish that TP53 is the single most frequently altered gene, that it is lost in more than 90% of tumours, or that most losses involve intron 1 rearrangements or deletions rather than point mutations. (LLM, conf=0.84)
- Partly supportedcites [38] Behjati, S. et al. Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma. Nat. Commun. 8, 15936 (2017). sourceExperimental — accuracy not yet measured
The Results section, “Chromothripsis amplification generates driver mutations” (page unavailable), reports TP53 disruption by copy-number loss or rearrangement breakpoints. It does not establish that TP53 is the single most frequently altered gene, is lost in more than 90% of osteosarcomas, or is lost predominantly through intron 1 changes or deletions rather than point mutations. (LLM, conf=0.87)
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Using these genomic aberrations to infer the evolution of the tumours, loss of TP53 and RB1 likely occurs early in the transformation process (with TP53 inactivation required to propagate abnormal genomes 39,40,41 ), followed by rapid accumulation of driver lesions such as MYC amplification, PTEN loss 42 and deletion of ATRX”
§ Osteosarcoma > Recurrent mutations
What the sources say
- Partly supportedcites [39] Overholtzer, M. et al. The presence of p53 mutations in human osteosarcomas correlates with high levels of genomic instability. Proc. Natl Acad. Sci. USA 100, 11547–11552 (2003). One of the first studies to show that p53 mutations correlate with high levels of genomic instability in osteosarcomas. sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked yetcites [40] Eischen, C. M. Genome stability requires p53. Cold Spring Harb. Perspect. Med. 6, a026096 (2016). source
- Partly supportedcites [41] Hanel, W. & Moll, U. M. Links between mutant p53 and genomic instability. J. Cell. Biochem. 113, 433–439 (2012). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [42] Gerstung, M. et al. The evolutionary history of 2,658 cancers. Nature 578, 122–128 (2020). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Patients who have received intensive, multidrug chemotherapy against osteosarcoma may have reduced antibody titres against vaccine-preventable infections for some months after chemotherapy, and some guidelines suggest measuring vaccine-induced antibody titres and repeating vaccinations 172,173 .”
§ Osteosarcoma > Late effects
What the sources say
- Not checked yetcites [172] Laws, H. J. et al. Impfen bei Immundefizienz : Anwendungshinweise zu den von der Ständigen Impfkommission empfohlenen Impfungen. (III) Impfen bei hämatologischen und onkologischen Erkrankungen (antineoplastische Therapie, Stammzelltransplantation), Organtransplantation und Asplenie [German]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 63, 588–644 (2020). source
- Partly supportedcites [173] Pittet, L. F. & Posfay-Barbe, K. M. Vaccination of immune compromised children-an overview for physicians. Eur. J. Pediatr. 180, 2035–2047 (2021). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“This work-up recommendation reveals lung metastases in 15-20% of patients, and occasionally identifies tumours within other bones or, very rarely, lesions at other sites.”
§ Osteosarcoma > Staging
What the sources say
- Not checked yetcites [107] Meyer, J. S. et al. Imaging guidelines for children with Ewing sarcoma and osteosarcoma: a report from the Children’s Oncology Group Bone Tumor Committee. Pediatr. Blood Cancer 51, 163–170 (2008). source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In these trials, MTKIs were effective in reducing PFS, becoming the mainstay of treatments for patients with relapsed disease.”
§ Osteosarcoma > Clinical research
What the sources say
- Not checked yetcites [12] Mirabello, L. et al. Frequency of pathogenic germline variants in cancer-susceptibility genes in patients with osteosarcoma. JAMA Oncol. 6, 724–734 (2020). This study demonstrates a high frequency of potentially pathogenic germline mutations in patients with osteosarcoma, supporting the role of germline genetic testing. source
- Not checked yetcites [159] Boddu, P. et al. Treated secondary acute myeloid leukemia: a distinct high-risk subset of AML with adverse prognosis. Blood Adv. 1, 1312–1323 (2017). source
- Not checked yetcites [160] Armstrong, G. T. et al. Late mortality among 5-year survivors of childhood cancer: a summary from the childhood cancer survivor study. J. Clin. Oncol. 27, 2328–2338 (2009). source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Osteosarcoma is the most common primary malignant tumour of the bone.”
§ Osteosarcoma > Abstract
What the sources say
- Not checked yetcites [1] Mirabello, L., Troisi, R. J. & Savage, S. A. Osteosarcoma incidence and survival rates from 1973 to 2004: data from the surveillance, epidemiology, and end results program. Cancer 115, 1531–1543 (2009). source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Osteosarcoma incidence is bimodal, peaking at 18 and 60 years of age”
§ Osteosarcoma > Abstract
What the sources say
- Not checked yetcites [1] Mirabello, L., Troisi, R. J. & Savage, S. A. Osteosarcoma incidence and survival rates from 1973 to 2004: data from the surveillance, epidemiology, and end results program. Cancer 115, 1531–1543 (2009). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Osteosarcoma is defined histologically as a tumour of osteoid-producing cells, which often exist within an admixture of adipogenic, muscle, spindle, fibroblastic and chondroblastic cells 3 .”
§ Osteosarcoma > Cellular origin
What the sources say
- Not checked yetcites [3] Klein, M. J. & Siegal, G. P. Osteosarcoma: anatomic and histologic variants. Am. J. Clin. Pathol. 125, 555–581 (2006). source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
In the paper
“with an incidence in children and adolescents of ~3-4.5 cases per million population per year 10 .”
§ Osteosarcoma > Epidemiology Incidence and mortality
What the sources say
- Not checked yetcites [10] Mirabello, L., Troisi, R. J. & Savage, S. A. International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons. Int. J. Cancer 125, 229–234 (2009). source
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Health disparities do not seem to have a major effect on survival outcomes but data are limited 17 .”
§ Osteosarcoma > Influence of age and sex
What the sources say
- Not checked yetcites [17] Ilcisin, L. A. S. et al. Poverty, race, ethnicity, and survival among U.S. children with non-metastatic osteosarcoma treated on EURAMOS-1: a report from the Children’s Oncology Group. J. Clin. Oncol. 40, 10004 (2022). source
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“It is particularly uncommon in young children <10 years of age in whom the genetic aetiology may be different to that in adolescents 12 .”
§ Osteosarcoma > Influence of age and sex
What the sources say
- Not checked yetcites [12] Mirabello, L. et al. Frequency of pathogenic germline variants in cancer-susceptibility genes in patients with osteosarcoma. JAMA Oncol. 6, 724–734 (2020). This study demonstrates a high frequency of potentially pathogenic germline mutations in patients with osteosarcoma, supporting the role of germline genetic testing. source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In addition, polygenic interactions may explain the association between tall stature and risk of osteosarcoma 24 .”
§ Osteosarcoma > Genetic predisposition
What the sources say
- Not checked yetcites [24] Mirabello, L. et al. Height at diagnosis and birth-weight as risk factors for osteosarcoma. Cancer Causes Control 22, 899–908 (2011). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“This genomic complexity has long been interpreted as a sign of chromosomal instability but emerging data suggest that the mechanisms triggering complexity are active early in the process of malignant transformation 35,37 .”
§ Osteosarcoma > Chromosomal complexity and copy number alterations
What the sources say
- Not checked yetcites [35] Sayles, L. C. et al. Genome-informed targeted therapy for osteosarcoma. Cancer Discov. 9, 46–63 (2019). A study that defines potentially actionable molecular subtypes of osteosarcoma. source
- Not checked yetcites [37] Rajan, S. et al. Remarkably stable copy-number profiles in osteosarcoma revealed using single-cell DNA sequencing. Preprint at bioRxiv https://doi.org/10.1101/2021.08.30.458268 (2021). source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“These rearrangements give rise to genome-wide copy number alterations, usually dominated by copy number loss, including of PTEN and CDKN2A/B, but with recurrent amplifications of MYC, VEGFA and CCNE1 (ref.35 ).”
§ Osteosarcoma > Chromosomal complexity and copy number alterations
What the sources say
- Not checked yetcites [35] Sayles, L. C. et al. Genome-informed targeted therapy for osteosarcoma. Cancer Discov. 9, 46–63 (2019). A study that defines potentially actionable molecular subtypes of osteosarcoma. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The genomic landscape of osteosarcoma tumours is usually dominated by widespread structural rearrangements, suggesting that several different mutational mechanisms, including chromothripsis, chromoplexy, kataegis and other structure-altering mechanisms, are involved 32,33,34 .”
§ Osteosarcoma > Chromosomal complexity and copy number alterations
What the sources say
- Not checked yetcites [32] Cortés-Ciriano, I. et al. Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing. Nat. Genet. 52, 331–341 (2020). source
- Not checked yetcites [33] Chen, X. et al. Recurrent somatic structural variations contribute to tumorigenesis in pediatric osteosarcoma. Cell Rep. 7, 104–112 (2014). The majority of TP53 loss in osteosarcoma occurs through intron 1 rearrangements or deletions rather than through point mutations. source
- Not checked yetcites [34] Perry, J. A. et al. Complementary genomic approaches highlight the PI3K/mTOR pathway as a common vulnerability in osteosarcoma. Proc. Natl Acad. Sci. USA 111, E5564–E5573 (2014). source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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It may state two separate claims as one.
In the paper
“Radiotherapy-associated osteosarcomas tend to occur within the radiation field following a long latency period of >10 years and are more frequent in patients with cancer predisposition syndromes such as Li-Fraumeni syndrome or hereditary retinoblastoma 25 .”
§ Osteosarcoma > Radiation and chemotherapy
What the sources say
- Not checked yetcites [25] Tucker, M. A. et al. Bone sarcomas linked to radiotherapy and chemotherapy in children. N. Engl. J. Med. 317, 588–593 (1987). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“it is estimated that malignant transformation to osteosarcoma occurs in ~1% of patients with Paget disease 26 .”
§ Osteosarcoma > Paget disease of bone and other predisposing conditions
What the sources say
- Not checked yetcites [26] Cundy, T. Paget’s disease of bone. Metabolism 80, 5–14 (2018). source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Osteosarcoma tumours often show signs of whole-genome duplication, which probably occurs in response to stresses imposed by pervasive copy number losses 36 .”
§ Osteosarcoma > Chromosomal complexity and copy number alterations
What the sources say
- Not checked yetcites [36] Wu, C. C. et al. Immuno-genomic landscape of osteosarcoma. Nat. Commun. 11, 1008 (2020). Molecular profiling of samples from patients with osteosarcoma characterizes immune subsets, including immune enrichment among older patients. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“The age-adjusted incidence rate was 1.9 per million for those aged 0-9 years, 6.7 per million for those aged 10-24 years, 1.9 per million for those aged 25-59 years and 2 per million for those aged ≥60 years.”
§ Osteosarcoma > Influence of age and sex
What the sources say
- Not checked yetcites [16] Cole, S., Gianferante, D. M., Zhu, B. & Mirabello, L. Osteosarcoma: a surveillance, epidemiology, and end results program‐based analysis from 1975 to 2017. Cancer 128, 2107–2118 (2022). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Osteosarcoma is slightly more common in males, with an average male-to-female ratio of 1.4:1 (ref.15 ).”
§ Osteosarcoma > Influence of age and sex
What the sources say
- Not checked yetcites [15] Brown, H. K., Schiavone, K., Gouin, F., Heymann, M.-F. & Heymann, D. Biology of bone sarcomas and new therapeutic developments. Calcif. Tissue Int. 102, 174–195 (2018). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In the USA, osteosarcoma accounts for <1% of all new cancer diagnoses with ~1,000 new cases diagnosed per year, half of these cases occurring in children and adolescents 1 .”
§ Osteosarcoma > Epidemiology Incidence and mortality
What the sources say
- Not checked yetcites [1] Mirabello, L., Troisi, R. J. & Savage, S. A. Osteosarcoma incidence and survival rates from 1973 to 2004: data from the surveillance, epidemiology, and end results program. Cancer 115, 1531–1543 (2009). source
plainn = 1,000- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“The incidence rise and peak in adolescents up to the age of 24 years are often attributed to the hormonal changes that occur during puberty with an earlier peak in girls than in boys 13 .”
§ Osteosarcoma > Influence of age and sex
What the sources say
- Not checked yetcites [13] Glass, A. G. & Fraumeni, J. F. Jr. Epidemiology of bone cancer in children. J. Natl Cancer Inst. 44, 187–199 (1970).
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Epidemiological observations support this interpretation as tumours were found to arise most frequently within the metaphyses of long bones in children, adolescents and young adults during times of peak linear growth, suggesting that the bone-producing and cartilage-producing cells that proliferate rapidly during those growth spurts are those susceptible to the transformation giving rise to osteos”
§ Osteosarcoma > Cellular origin
What the sources say
- Not checked yetcites [29] Jones, K. B. Osteosarcomagenesis: modeling cancer initiation in the mouse. Sarcoma 2011, 694136 (2011). source
- Not checked yetcites [30] Mutsaers, A. J. & Walkley, C. R. Cells of origin in osteosarcoma: mesenchymal stem cells or osteoblast committed cells? Bone 62, 56–63 (2014). source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Whether these benign bone tumours trigger a transformation based on the accumulation of genetic and epigenetic events or the creation of an environment permissive to malignant transformation remains unclear 28 .”
§ Osteosarcoma > Paget disease of bone and other predisposing conditions
What the sources say
- Not checked yetcites [28] Picci, P. et al. Late sarcoma development after curettage and bone grafting of benign bone tumors. Eur. J. Radiol. 77, 19–25 (2011). source
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“in patients with metastatic disease, event-free survival outcomes remain poor at less than 30%.”
§ Osteosarcoma > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Notably, the incidence of osteosarcoma in children and adolescents has increased from the 1970s to the 2000s but has declined in adults >60 years of age.”
§ Osteosarcoma > Influence of age and sex
What the sources say
- Not checked yetcites [16] Cole, S., Gianferante, D. M., Zhu, B. & Mirabello, L. Osteosarcoma: a surveillance, epidemiology, and end results program‐based analysis from 1975 to 2017. Cancer 128, 2107–2118 (2022). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Particularly in older adults, osteosarcomas may also arise in the setting of Paget disease of bone and other bone disorders, suggesting a role of abnormal bone turnover in osteosarcoma pathogenesis 26 .”
§ Osteosarcoma > Paget disease of bone and other predisposing conditions
What the sources say
- Not checked yetcites [26] Cundy, T. Paget’s disease of bone. Metabolism 80, 5–14 (2018). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The frequency of germline mutations in patients with osteosarcoma ranges from 18% to 28% and these mutations are more common in younger patients 12,18 .”
§ Osteosarcoma > Genetic predisposition
What the sources say
- Not checked yetcites [12] Mirabello, L. et al. Frequency of pathogenic germline variants in cancer-susceptibility genes in patients with osteosarcoma. JAMA Oncol. 6, 724–734 (2020). This study demonstrates a high frequency of potentially pathogenic germline mutations in patients with osteosarcoma, supporting the role of germline genetic testing. source
- Not checked yetcites [18] Zhang, J. et al. Germline mutations in predisposition genes in pediatric cancer. N. Engl. J. Med. 373, 2336–2346 (2015). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Osteosarcoma incidence has a bimodal age distribution with a primary peak in adolescents and young adults and a second, smaller peak in the seventh and eighth decade of life 1”
§ Osteosarcoma > Influence of age and sex
What the sources say
- Not checked yetcites [1] Mirabello, L., Troisi, R. J. & Savage, S. A. Osteosarcoma incidence and survival rates from 1973 to 2004: data from the surveillance, epidemiology, and end results program. Cancer 115, 1531–1543 (2009). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Patients with retinoblastoma and Rothmund-Thomson syndrome might present with osteosarcoma in their teens, and osteosarcoma associated with Werner syndrome or Li-Fraumeni syndrome presents in middle age 22,23 .”
§ Osteosarcoma > Genetic predisposition
What the sources say
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“A major caveat is that each of these alterations only applies to a very limited number of patients, making clinical trials of these subgroups challenging, and many more common alterations are not associated with targetable therapies.”
§ Osteosarcoma > Drivers of disease and potential targets
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“Osteosarcoma development can be described by the conjunction of multiple factors: oncogenic events that initiate malignant transformation, a progressive increase of genetic aberrations with the increasing proliferation rate of cells committed towards the osteoblast lineage during bone growth 44 , and involvement of a permissive microenvironment, which is a prerequisite for the growth of cancer”
§ Osteosarcoma > Malignant progression and metastasis
What the sources say
- Not checked yetcites [44] Kovac, M. et al. Exome sequencing of osteosarcoma reveals mutation signatures reminiscent of BRCA deficiency. Nat. Commun. 6, 8940 (2015). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“deletion of ATRX, which seems to activate alternative lengthening of telomeres and is associated with decreased survival 36,43 .”
§ Osteosarcoma > Recurrent mutations
What the sources say
- Not checked yetcites [36] Wu, C. C. et al. Immuno-genomic landscape of osteosarcoma. Nat. Commun. 11, 1008 (2020). Molecular profiling of samples from patients with osteosarcoma characterizes immune subsets, including immune enrichment among older patients. source
- Not checked yetcites [43] Lawlor, R. T. et al. Alternative lengthening of telomeres (ALT) influences survival in soft tissue sarcomas: a systematic review with meta-analysis. BMC Cancer 19, 232 (2019). source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Osteosarcoma cells educate these MSCs by secreting TGFβ-containing extracellular vesicles 60 , triggering MSC IL-6 release and activating a STAT3-mediated tumour progression programme that drives the formation of metastatic foci within the lung 61 .”
§ Osteosarcoma > Malignant progression and metastasis
What the sources say
- Not checked yetcites [60] Baglio, S. R. et al. Blocking tumor-educated MSC paracrine activity halts osteosarcoma progression. Clin. Cancer Res. 23, 3721–3733 (2017). source
- Not checked yetcites [61] Tu, B., Du, L., Fan, Q. M., Tang, Z. & Tang, T. T. STAT3 activation by IL-6 from mesenchymal stem cells promotes the proliferation and metastasis of osteosarcoma. Cancer Lett. 325, 80–88 (2012). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The dialogue between osteosarcoma cells and their microenvironment is crucial for tumour growth at the bone site and is associated with direct interaction among mesenchymal, vascular and immune cells (depending on cell differentiation level) 45 , the interaction of cells with soluble factors such as chemokines and cytokines 46 , and the interaction of cells with extracellular vesicles 47 .”
§ Osteosarcoma > Malignant progression and metastasis
What the sources say
- Not checked yetcites [45] Tellez-Gabriel, M. et al. Analysis of gap junctional intercellular communications using a dielectrophoresis-based microchip. Eur. J. Cell Biol. 96, 110–118 (2017). source
- Not checked yetcites [46] Bénédicte Brounais, L.-R. & Frédéric, L. In Bone Cancer 221–239, Ch. 18 (Academic Press, 2022).
- Not checked yetcites [47] Lan, M. et al. Extracellular vesicles-mediated signaling in the osteosarcoma microenvironment: roles and potential therapeutic targets. J. Bone Oncol. 12, 101–104 (2018). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This seed and soil phenomenon is driven by a microenvironment that modulates osteosarcoma cell behaviour and facilitates proliferation, quiescence, invasion, migration, and drug resistance 15,51,52,53 and contributes to their intrinsic heterogeneity 54,55 .”
§ Osteosarcoma > Malignant progression and metastasis
What the sources say
- Not checked yetcites [15] Brown, H. K., Schiavone, K., Gouin, F., Heymann, M.-F. & Heymann, D. Biology of bone sarcomas and new therapeutic developments. Calcif. Tissue Int. 102, 174–195 (2018). source
- Not checked yetcites [51] Heymann, M.-F., Lézot, F. & Heymann, D. The contribution of immune infiltrates and the local microenvironment in the pathogenesis of osteosarcoma. Cell. Immunol. https://doi.org/10.1016/j.cellimm.2017.10.011 (2017). source
- Not checked yetcites [52] Brown, H. K., Tellez-Gabriel, M. & Heymann, D. Cancer stem cells in osteosarcoma. Cancer Lett. 386, 189–195 (2017). source
- Not checked yetcites [53] Grunewald, T. G. et al. Sarcoma treatment in the era of molecular medicine. EMBO Mol. Med. 12, e11131 (2020). source
- Not checked yetcites [54] Zhou, Y. et al. Single-cell RNA landscape of intratumoral heterogeneity and immunosuppressive microenvironment in advanced osteosarcoma. Nat. Commun. 11, 6322 (2020). source
- Not checked yetcites [55] Guo, J. et al. Single-cell profiling of tumor microenvironment heterogeneity in osteosarcoma identifies a highly invasive subcluster for predicting prognosis. Front. Oncol. 12, 732862 (2022). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“large-scale sequencing has identified only moderate levels of point mutations with few recurrently mutated genes 33,34,36,38 .”
§ Osteosarcoma > Recurrent mutations
What the sources say
- Not checked yetcites [33] Chen, X. et al. Recurrent somatic structural variations contribute to tumorigenesis in pediatric osteosarcoma. Cell Rep. 7, 104–112 (2014). The majority of TP53 loss in osteosarcoma occurs through intron 1 rearrangements or deletions rather than through point mutations. source
- Not checked yetcites [34] Perry, J. A. et al. Complementary genomic approaches highlight the PI3K/mTOR pathway as a common vulnerability in osteosarcoma. Proc. Natl Acad. Sci. USA 111, E5564–E5573 (2014). source
- Not checked yetcites [36] Wu, C. C. et al. Immuno-genomic landscape of osteosarcoma. Nat. Commun. 11, 1008 (2020). Molecular profiling of samples from patients with osteosarcoma characterizes immune subsets, including immune enrichment among older patients. source
- Not checked yetcites [38] Behjati, S. et al. Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma. Nat. Commun. 8, 15936 (2017). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“However, the overall role of osteoclasts in osteosarcoma development remains unclear as they seem to hold a pro-tumorigenic role in early-stage disease 48 but an opposite role in later-stage disease 49 .”
§ Osteosarcoma > Malignant progression and metastasis
What the sources say
- Not checked yetcites [48] Cackowski, F. C. et al. Osteoclasts are important for bone angiogenesis. Blood 115, 140–149 (2010). source
- Not checked yetcites [49] Endo-Munoz, L., Evdokiou, A. & Saunders, N. A. The role of osteoclasts and tumour-associated macrophages in osteosarcoma metastasis. Biochim. Biophys. Acta 1826, 434–442 (2012).
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The most likely order of events for osteosarcoma evolution is loss of TP53 and RB1 as early events, of which TP53 loss is likely the initiator of genomic instability 39,40,41 followed by whole-genome doubling, gain of 8q (CMYC) and loss of 10q (PTEN) 42 .”
§ Osteosarcoma > Malignant progression and metastasis
What the sources say
- Not checked yetcites [39] Overholtzer, M. et al. The presence of p53 mutations in human osteosarcomas correlates with high levels of genomic instability. Proc. Natl Acad. Sci. USA 100, 11547–11552 (2003). One of the first studies to show that p53 mutations correlate with high levels of genomic instability in osteosarcomas. source
- Not checked yetcites [40] Eischen, C. M. Genome stability requires p53. Cold Spring Harb. Perspect. Med. 6, a026096 (2016). source
- Not checked yetcites [41] Hanel, W. & Moll, U. M. Links between mutant p53 and genomic instability. J. Cell. Biochem. 113, 433–439 (2012). source
- Not checked yetcites [42] Gerstung, M. et al. The evolutionary history of 2,658 cancers. Nature 578, 122–128 (2020). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The cytoskeletal linker ezrin provides a scaffold for PI3K-AKT signalling and facilitates survival through the stresses that disseminated tumour cells first encounter within the lung 72,73,74 .”
§ Osteosarcoma > Malignant progression and metastasis
What the sources say
- Not checked yetcites [72] Khanna, C. et al. The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. Nat. Med. 10, 182–186 (2004). source
- Not checked yetcites [73] Bulut, G. et al. Small molecule inhibitors of ezrin inhibit the invasive phenotype of osteosarcoma cells. Oncogene 31, 269–281 (2012). source
- Not checked yetcites [74] Ren, L. et al. Dysregulation of Ezrin phosphorylation prevents metastasis and alters cellular metabolism in osteosarcoma. Cancer Res. 72, 1001–1012 (2012). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Mesenchymal stem cells (MSCs) have been implicated in osteosarcoma metastasis and therapeutic resistance 57,58,59 .”
§ Osteosarcoma > Malignant progression and metastasis
What the sources say
- Not checked yetcites [57] Stamatopoulos, A. et al. Mesenchymal stromal cells for bone sarcoma treatment: roadmap to clinical practice. J. Bone Oncol. 16, 100231 (2019). source
- Not checked yetcites [58] Perrot, P. et al. Safety concern between autologous fat graft, mesenchymal stem cell and osteosarcoma recurrence. PLoS ONE 5, e10999 (2010). source
- Not checked yetcites [59] Cortini, M., Avnet, S. & Baldini, N. Mesenchymal stroma: role in osteosarcoma progression. Cancer Lett. 405, 90–99 (2017). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Skeletal imaging with PET or technetium bone scans is important to identify covert bony disease 107 .”
§ Osteosarcoma > Staging
What the sources say
- Not checked yetcites [107] Meyer, J. S. et al. Imaging guidelines for children with Ewing sarcoma and osteosarcoma: a report from the Children’s Oncology Group Bone Tumor Committee. Pediatr. Blood Cancer 51, 163–170 (2008). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“Staging is guided primarily by the Musculoskeletal Tumour Society (MSTS) staging system for sarcomas 108 , which defines tumours as being either low or high grade, confined to an anatomic compartment or violating anatomic barriers, and localized or metastatic.”
§ Osteosarcoma > Staging
What the sources say
- Not checked yetcites [108] Wolf, R. E. & Enneking, W. F. The staging and surgery of musculoskeletal neoplasms. Orthop. Clin. North. Am. 27, 473–481 (1996). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The response to neoadjuvant chemotherapy, assessed in the definitive resection specimen, has clear prognostic value and has been used in previous clinical trials to stratify patients into good responders and poor responders; however, intensification of treatment did not improve outcomes in the poor responder group 114 .”
§ Osteosarcoma > Prognosis
What the sources say
- Not checked yetcites [114] Marina, N. M. et al. Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial. Lancet Oncol. 17, 1396–1408 (2016). An international randomized clinical trial fails to show benefit of addition of I/E to MAP chemotherapy in the primary treatment of osteosarcoma. source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The loss of structural integrity due to tumour-related osteolysis puts patients at risk for pathological fractures, which occur in ~10% of patients and can complicate initial management 102 .”
§ Osteosarcoma > Presentation
What the sources say
- Not checked yetcites [102] Zhou, Y. et al. The effect of pathological fractures on the prognosis of patients with osteosarcoma: a meta-analysis of 14 studies. Oncotarget 8, 73037–73049 (2017). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Indeed, IGF1 receptor amplifications occur in up to 14% of patients with osteosarcoma 38 , which seems to drive activation of the PI3K-AKT-mTOR pathway through the MAPK pathway 98 .”
§ Osteosarcoma > Cytokines and growth factors
What the sources say
- Not checked yetcites [38] Behjati, S. et al. Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma. Nat. Commun. 8, 15936 (2017). source
- Not checked yetcites [98] Li, Y. S., Liu, Q., He, H. B. & Luo, W. The possible role of insulin-like growth factor-1 in osteosarcoma. Curr. Probl. Cancer 43, 228–235 (2019). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Copy number amplifications of potentially targetable genes seemed to predict sensitivity to specific agents 35 ; however, subsequent work has shown that the picture is much more complicated 9 .”
§ Osteosarcoma > Genetic alterations
What the sources say
- Not checked yetcites [35] Sayles, L. C. et al. Genome-informed targeted therapy for osteosarcoma. Cancer Discov. 9, 46–63 (2019). A study that defines potentially actionable molecular subtypes of osteosarcoma. source
- Not checked yetcites [9] Gill, J. & Gorlick, R. Advancing therapy for osteosarcoma. Nat. Rev. Clin. Oncol. 18, 609–624 (2021). source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The promising preclinical successes seen with CDK12 inhibitors 92 and drugs that block protein elongation 93 may not be surprising as osteosarcoma cells depend on massive levels of protein production.”
§ Osteosarcoma > Cell cycle transcriptional and translational targets
What the sources say
- Not checked yetcites [92] Bayles, I. et al. Ex vivo screen identifies CDK12 as a metastatic vulnerability in osteosarcoma. J. Clin. Invest. 129, 4377–4392 (2019). source
- Not checked yetcites [93] Chang, L.-S. et al. Targeting protein translation by rocaglamide and didesmethylrocaglamide to treat MPNST and other sarcomas. Mol. Cancer Ther. 19, 731–741 (2020). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Patients experiencing fractures have higher rates of lung metastasis, both at presentation and subsequent to treatment 102 .”
§ Osteosarcoma > Prognosis
What the sources say
- Not checked yetcites [102] Zhou, Y. et al. The effect of pathological fractures on the prognosis of patients with osteosarcoma: a meta-analysis of 14 studies. Oncotarget 8, 73037–73049 (2017). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Most patients present with high-grade lesions that have both bony and soft tissue components, making the presence or absence of metastasis the primary risk-stratifying feature at diagnosis.”
§ Osteosarcoma > Staging
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Most osteosarcoma patients present with high-grade lesions that have both bony and soft tissue components.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For core needle biopsies, adequate sampling of the tissue has to be ensured as osteosarcoma lesions can be quite heterogeneous and diagnostic features (such as malignant osteoid) can vary from sample to sample.”
§ Osteosarcoma > Biopsy and pathology
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Rests on an assumption: Osteosarcoma lesions are heterogeneous and diagnostic features such as malignant osteoid vary from sample to sample.
In the paper
“In 2008, guidelines from the Children's Oncology Group were published 107 , and are still widely accepted, advocating PET imaging with accompanying whole-body CT or whole-body MRI, with isotope bone scans if these modalities are not available.”
§ Osteosarcoma > Staging
What the sources say
- Not checked yetcites [107] Meyer, J. S. et al. Imaging guidelines for children with Ewing sarcoma and osteosarcoma: a report from the Children’s Oncology Group Bone Tumor Committee. Pediatr. Blood Cancer 51, 163–170 (2008). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“There has been a long-standing interest in immune-based therapies centred on the activity of mifamurtide in osteosarcoma in phase II and subsequently on a randomized phase III trial conducted by the Children's Oncology Group 81 .”
§ Osteosarcoma > Immune approaches
What the sources say
- Not checked yetcites [81] Meyers, P. A. et al. Osteosarcoma: the addition of muramyl tripeptide to chemotherapy improves overall survival — a report from the Children’s Oncology Group. J. Clin. Oncol. 26, 633–638 (2008). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“A small number of patients present with localized, lower-grade parosteal and periosteal lesions 109,110 .”
§ Osteosarcoma > Staging
What the sources say
- Not checked yetcites [109] Sheth, D. S. et al. Conventional and dedifferentiated parosteal osteosarcoma. Diagnosis, treatment, and outcome. Cancer 78, 2136–2145 (1996). source
- Not checked yetcites [110] Grimer, R. J. et al. Periosteal osteosarcoma — a European review of outcome. Eur. J. Cancer 41, 2806–2811 (2005). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Patients who present with lung metastasis have the worst prognosis, with 3-year survival rates of <30% 113 .”
§ Osteosarcoma > Prognosis
What the sources say
- Not checked yetcites [113] Aljubran, A. H., Griffin, A., Pintilie, M. & Blackstein, M. Osteosarcoma in adolescents and adults: survival analysis with and without lung metastases. Ann. Oncol. 20, 1136–1141 (2009). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The genomic complexity of osteosarcoma might suggest sensitivity to immune modulators such as immune-checkpoint inhibitors (ICIs) but the overall mutational burden within most osteosarcomas is markedly less than that associated with responses to immune-checkpoint inhibition in other adult tumours 83 .”
§ Osteosarcoma > Immune approaches
What the sources say
- Not checked yetcites [83] Gröbner, S. N. et al. The landscape of genomic alterations across childhood cancers. Nature 555, 321–327 (2018). source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Fine-needle aspirates are usually inadequate for a definitive diagnosis of osteosarcoma due to the lack of sufficient histological context and the resulting difficulty to assess tumour grade, and are therefore not recommended.”
§ Osteosarcoma > Biopsy and pathology
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Fine-needle aspirates lack sufficient histological context and make tumour grade assessment difficult.
None of the sources cited for this claim have been checked yet.
In the paper
“The definition of good responder and poor responder to chemotherapy varies depending on the study.”
§ Osteosarcoma > Prognosis
What the sources say
- Not checked yetcites [115] Rosen, G., Murphy, M. L., Huvos, A. G., Gutierrez, M. & Marcove, R. C. Chemotherapy, en bloc resection, and prosthetic bone replacement in the treatment of osteogenic sarcoma. Cancer 37, 1–11 (1976). source
- Not checked yetcites [116] Rosen, G. et al. Preoperative chemotherapy for osteogenic sarcoma: selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy. Cancer 49, 1221–1230 (1982). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“All patients presenting with newly diagnosed disease should undergo CT imaging of the chest, which has the highest efficiency in identifying lung nodules (Fig. 6g).”
§ Osteosarcoma > Staging
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“The workup for the presenting symptoms usually includes plain-film radiographs, potentially revealing large lesions that are causing destruction of normal trabecular bone with poorly defined margins 103”
§ Osteosarcoma > Imaging
What the sources say
- Not checked yetcites [103] Papagelopoulos, P. J. et al. Current concepts in the evaluation and treatment of osteosarcoma. Orthopedics 23, 858–867 (2000). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Local recurrence rates for extremity osteosarcoma are low and generally less than 5%, suggesting that, in most cases, complete resection is achieved.”
§ Osteosarcoma > Surgery
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This applies to both patients with localized disease and those with primary metastatic osteosarcoma, provided complete surgical removal of all known metastatic deposits has been achieved.”
§ Osteosarcoma > Management
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Combination chemotherapy and complete surgical resection are essential for cure in osteosarcoma.
None of the sources cited for this claim have been checked yet.
In the paper
“Some studies suggested that the histological subtype of osteosarcoma can influence the degree of necrosis, with chondroblastic and telangiectatic subtypes having less necrosis but those differences have not translated into improvement in survival 1,118 .”
§ Osteosarcoma > Prognosis
What the sources say
- Not checked yetcites [1] Mirabello, L., Troisi, R. J. & Savage, S. A. Osteosarcoma incidence and survival rates from 1973 to 2004: data from the surveillance, epidemiology, and end results program. Cancer 115, 1531–1543 (2009). source
- Not checked yetcites [118] Bacci, G. et al. Neoadjuvant chemotherapy for high-grade central osteosarcoma of the extremity. Cancer 97, 3068–3075 (2003). source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“No specific blood-based biomarkers or routine imaging for screening and early detection of osteosarcoma exist.”
§ Osteosarcoma > Screening and prevention
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Low-grade lesions, including low-grade central lesions, are treated by local surgical control only.”
§ Osteosarcoma > Systemic therapy at diagnosis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Molecular features that identify patients at higher risk include RB1 loss, MYC amplification and VEGFA amplification, among others.”
§ Osteosarcoma > Prognosis
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“However, considerable chemotherapy-related toxic effects were observed; neutropenia and other haematological adverse effects were most frequent.”
§ Osteosarcoma > Systemic therapy at diagnosis
What the sources say
- Not checked yetcites [133] Ferrari, S. et al. EURO-B.O.S.S.: a European study on chemotherapy in bone-sarcoma patients aged over 40: Outcome in primary high-grade osteosarcoma. Tumori 104, 30–36 (2018). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Identification of individuals at risk enables adherence to clinical practice guidelines and early identification and risk reduction for osteosarcoma as well as other cancers 120 .”
§ Osteosarcoma > Screening and prevention
What the sources say
- Not checked yetcites [120] Villani, A. et al. Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study. Lancet Oncol. 17, 1295–1305 (2016). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Limb salvage is feasible for most patients with extremity tumours via reconstruction using an endoprosthetic implant, or allogeneic or autologous bone graft.”
§ Osteosarcoma > Surgery
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“The most efficacious regimens employ at least three of these drugs, yet adding a fourth agent may not lead to further benefits 128 .”
§ Osteosarcoma > Systemic therapy at diagnosis
What the sources say
- Not checked yetcites [128] Anninga, J. K. et al. Chemotherapeutic adjuvant treatment for osteosarcoma: where do we stand? Eur. J. Cancer 47, 2431–2445 (2011). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Given that therapy changes based on necrosis grading have not been shown to modify survival outcomes, the use of necrosis grading has declined.”
§ Osteosarcoma > Prognosis
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In addition, patients with unresectable primary or metastatic disease at diagnosis and those with disease relapse have extremely poor outcomes 2,126 .”
§ Osteosarcoma > Management
What the sources say
- Not checked yetcites [2] Bielack, S. S. et al. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J. Clin. Oncol. 20, 776–790 (2002). A study that affirms tumour site and size, primary metastases, response to chemotherapy, and surgical remission as independent prognostic factors in patients with osteosarcoma. source
- Not checked yetcites [126] Kempf-Bielack, B. et al. Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS). J. Clin. Oncol. 23, 559–568 (2005). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The improvement in prognosis seems linear with increasing necrosis, with some studies setting the cut-off point between good and poor between grades 2 and 3, whereas others have set it between grades 3 and 4.”
§ Osteosarcoma > Prognosis
What the sources say
- Not checked yetcites [117] Bishop, M. W. et al. Assessing the prognostic significance of histologic response in osteosarcoma: a comparison of outcomes on CCG-782 and INT0133 — a report from the Children’s Oncology Group Bone Tumor Committee. Pediatr. Blood Cancer 63, 1737–1743 (2016). This study validates the prognostic significance of pathological treatment response in osteosarcoma following neoadjuvant chemotherapy. source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Intermediate-grade lesions, including periosteal lesions and most osteosarcomas that affect the jaw, similarly need local control, which is also typically surgery.”
§ Osteosarcoma > Systemic therapy at diagnosis
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Minimally invasive and non-invasive growing implants enable limb-salvage reconstruction as well as future limb-length equality for patients with skeletal immaturity 135 .”
§ Osteosarcoma > Surgery
What the sources say
- Not checked yetcites [135] Ruggieri, P. et al. Outcome of expandable prostheses in children. J. Pediatr. Orthop. 33, 244–253 (2013). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Otherwise, intralesional or marginal resections increase local recurrence rate, which is associated with reduced overall survival 2,134 .”
§ Osteosarcoma > Surgery
What the sources say
- Not checked yetcites [2] Bielack, S. S. et al. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J. Clin. Oncol. 20, 776–790 (2002). A study that affirms tumour site and size, primary metastases, response to chemotherapy, and surgical remission as independent prognostic factors in patients with osteosarcoma. source
- Not checked yetcites [134] Picci, P. et al. Relationship of chemotherapy-induced necrosis and surgical margins to local recurrence in osteosarcoma. J. Clin. Oncol. 12, 2699–2705 (1994). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Guidelines for patients and families with Li-Fraumeni syndrome include annual whole-body MRI to screen for multiple possible malignancies, including sarcomas, and maintaining a high index of suspicion for rare cancers 122 .”
§ Osteosarcoma > Screening and prevention
What the sources say
- Not checked yetcites [122] Kratz, C. P. et al. Cancer screening recommendations for individuals with Li-Fraumeni syndrome. Clin. Cancer Res. 23, e38–e45 (2017). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Osteosarcomas in other craniofacial locations can be high grade, and are treated with chemotherapy and local control in such case.”
§ Osteosarcoma > Systemic therapy at diagnosis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Intensive blood and imaging-based surveillance in patients with pathogenic germline TP53 variants has been shown to be feasible, resulting in the detection of solid tumours at an earlier stage and associated with improved long-term survival, although these findings were not specific to osteosarcoma 120 .”
§ Osteosarcoma > Screening and prevention
What the sources say
- Not checked yetcites [120] Villani, A. et al. Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study. Lancet Oncol. 17, 1295–1305 (2016). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“There is no standard-of-care systemic therapy for patients >40 years of age with a poor outcome and few clinical trials to inform practice 132 .”
§ Osteosarcoma > Systemic therapy at diagnosis
What the sources say
- Not checked yetcites [132] Grimer, R. J. et al. Osteosarcoma over the age of forty. Eur. J. Cancer 39, 157–163 (2003). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Here, the number of metastases and completeness of excision seem to affect outcomes 6 .”
§ Osteosarcoma > Surgery
What the sources say
- Not checked yetcites [6] Kager, L. et al. Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. J. Clin. Oncol. 21, 2011–2018 (2003). source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Progress was only made with the introduction of systemic chemotherapy, which was soon administered neoadjuvantly 127 .”
§ Osteosarcoma > Systemic therapy at diagnosis
What the sources say
- Not checked yetcites [127] Jaffe, N., Puri, A. & Gelderblom, H. Osteosarcoma: evolution of treatment paradigms. Sarcoma 2013, 203531 (2013). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Surgery is also an important local control modality for metastatic sites, with long-term survival improving with the resection of lung metastases.”
§ Osteosarcoma > Surgery
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Retrospective analysis of the European Musculoskeletal Oncology Society of patients over 40 years did demonstrate that adult patients may benefit from aggressive treatment with surgery and chemotherapy, with outcomes possibly being related to decreased chemotherapy administered to some of the elderly patients 132 .”
§ Osteosarcoma > Systemic therapy at diagnosis
What the sources say
- Not checked yetcites [132] Grimer, R. J. et al. Osteosarcoma over the age of forty. Eur. J. Cancer 39, 157–163 (2003). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The dosage of chemotherapy given before surgery shifts the degree of necrosis but it does not change the prognostic value of necrosis grading nor influence survival 119 .”
§ Osteosarcoma > Prognosis
What the sources say
- Not checked yetcites [119] Meyers, P. A. et al. Intensification of preoperative chemotherapy for osteogenic sarcoma: results of the Memorial Sloan-Kettering (T12) protocol. J. Clin. Oncol. 16, 2452–2458 (1998). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“For intermediate-grade osteosarcomas, the role of chemotherapy is controversial and certainly not associated with the same risk-to-benefit relationship as high-grade osteosarcomas.”
§ Osteosarcoma > Systemic therapy at diagnosis
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“For example, necrosis grading had four levels but each level was only defined descriptively 115,116 and percentages were added later to facilitate comparison 116 .”
§ Osteosarcoma > Prognosis
What the sources say
- Not checked yetcites [115] Rosen, G., Murphy, M. L., Huvos, A. G., Gutierrez, M. & Marcove, R. C. Chemotherapy, en bloc resection, and prosthetic bone replacement in the treatment of osteogenic sarcoma. Cancer 37, 1–11 (1976). source
- Not checked yetcites [116] Rosen, G. et al. Preoperative chemotherapy for osteogenic sarcoma: selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy. Cancer 49, 1221–1230 (1982). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Treatment for anthracycline-induced heart failure is similar to that of heart failure from any cause 164 .”
§ Osteosarcoma > Late effects
What the sources say
- Not checked yetcites [164] Armenian, S. H. et al. Recommendations for cardiomyopathy surveillance for survivors of childhood cancer: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group. Lancet Oncol. 16, e123–e136 (2015). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Ablative surgery (amputation) may be associated with poor joint function but usually involves fewer episodes of revision surgery than limb salvage.”
§ Osteosarcoma > Late effects
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Osteosarcoma recurs most often in the lung followed by bone at a site distant to the primary tumour.”
§ Osteosarcoma > Relapsed osteosarcoma
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The cumulative anthracycline dose is a major risk factor for severe cardiomyopathy development but young age at treatment, female sex, peak drug exposure and additional stress to the heart have also been implicated 161,162,163 .”
§ Osteosarcoma > Late effects
What the sources say
- Not checked yetcites [161] Mancilla, T. R., Iskra, B. & Aune, G. J. Doxorubicin-induced cardiomyopathy in children. Compr. Physiol. 9, 905–931 (2019). source
- Not checked yetcites [162] Bhagat, A. & Kleinerman, E. S. Anthracycline-induced cardiotoxicity: causes, mechanisms, and prevention. Adv. Exp. Med. Biol. 1257, 181–192 (2020). source
- Not checked yetcites [163] Rawat, P. S., Jaiswal, A., Khurana, A., Bhatti, J. S. & Navik, U. Doxorubicin-induced cardiotoxicity: an update on the molecular mechanism and novel therapeutic strategies for effective management. Biomed. Pharmacother. 139, 111708 (2021). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The regimens include high-dose ifosfamide with or without etoposide and gemcitabine and docetaxel.”
§ Osteosarcoma > Relapsed osteosarcoma
What the sources say
- Not checked yetcites [104] Strauss, S. J. et al. Bone sarcomas: ESMO-EURACAN-GENTURIS-ERN PaedCan Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann. Oncol. 32, 1520–1536 (2021). source
- Not checked yetcites [141] NCCN. Treatment by cancer type. NCCN https://www.nccn.org/guidelines/category_1 (2022).
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Among all paediatric patients with cancer, those with osteosarcoma carry one of the highest rates of genetic cancer predisposition (10-20%) 12 ; Li-Fraumeni syndrome is the most prominent but hereditary retinoblastoma, helicase-associated cancers and others also contribute 157 .”
§ Osteosarcoma > Late effects
What the sources say
- Not checked yetcites [157] Kratz, C. P. et al. Predisposition to cancer in children and adolescents. Lancet Child Adolesc. Health 5, 142–154 (2021). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Anthracycline-induced, severe cardiomyopathy is another common, potentially fatal late effect of chemotherapy, with ~2% of non-relapse-related deaths among childhood cancer survivors attributed to cardiomyopathy or heart failure 160 .”
§ Osteosarcoma > Late effects
What the sources say
- Not checked yetcites [160] Armstrong, G. T. et al. Late mortality among 5-year survivors of childhood cancer: a summary from the childhood cancer survivor study. J. Clin. Oncol. 27, 2328–2338 (2009). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Trials combining ICIs with other anticancer therapies, such as MTKIs, and trials of other immune activation approaches, such as antibody combinations and cellular therapy, in individuals with osteosarcoma are in early stages 9 .”
§ Osteosarcoma > Relapsed osteosarcoma
What the sources say
- Not checked yetcites [9] Gill, J. & Gorlick, R. Advancing therapy for osteosarcoma. Nat. Rev. Clin. Oncol. 18, 609–624 (2021). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Local recurrence is rare; for example, it accounted for only 7% of all events in almost 1,000 patients who had an event in EURAMOS-1 (ref.125 ).”
§ Osteosarcoma > Relapsed osteosarcoma
What the sources say
- Not checked yetcites [125] Smeland, S. et al. Survival and prognosis with osteosarcoma: outcomes in more than 2000 patients in the EURAMOS-1 (European and American Osteosarcoma Study) cohort. Eur. J. Cancer 109, 36–50 (2019). source
plainn = 1,000- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The phase I trial of this combination demonstrated tolerability and a 4-month PFS of 51% 150 .”
§ Osteosarcoma > Relapsed osteosarcoma
What the sources say
- Not checked yetcites [150] Gaspar, N. et al. Lenvatinib with etoposide plus ifosfamide in patients with refractory or relapsed osteosarcoma (ITCC-050): a multicentre, open-label, multicohort, phase 1/2 study. Lancet Oncol. 22, 1312–1321 (2021). source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The mechanism of action of MTKIs in osteosarcoma is still not well understood and correlative translational studies have yet to identify predictive biomarkers of response to MTKIs.”
§ Osteosarcoma > Relapsed osteosarcoma
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“These features include the presence of COSMIC mutational signature 3 (ref. 154 ), possibly representing defective DNA damage response in osteosarcoma, in ~30% of cases, and the frequent presence of genomic events that lead to replication stress such as MYC amplification and CCNE1 amplification.”
§ Osteosarcoma > Relapsed osteosarcoma
What the sources say
- Not checked yetcites [154] Alexandrov, L. B. et al. The repertoire of mutational signatures in human cancer. Nature 578, 94–101 (2020). source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Even the most modern endoprostheses have a limited lifespan as mechanical wear or infections require repeated operations in most patients who undergo limb salvage.”
§ Osteosarcoma > Late effects
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Secondary cancers are frequently acute myeloid leukaemias 155 , which may be caused by previous exposure to DNA-damaging alkylators, often arising after a median of around 7 years after initial treatment 158 .”
§ Osteosarcoma > Late effects
What the sources say
- Not checked yetcites [155] Hecker-Nolting, S., Langer, T., Blattmann, C., Kager, L. & Bielack, S. S. Current insights into the management of late chemotherapy toxicities in pediatric osteosarcoma patients. Cancer Manag. Res. 13, 8989–8998 (2021). source
- Not checked yetcites [158] Leone, G., Pagano, L., Ben-Yehuda, D. & Voso, M. T. Therapy-related leukemia and myelodysplasia: susceptibility and incidence. Haematologica 92, 1389–1398 (2007). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Osteosarcoma surgery is usually associated with loss of a major joint, most often the knee.”
§ Osteosarcoma > Late effects
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“As a class, multi-target tyrosine kinase inhibitors (MTKIs) demonstrate activity in recurrent osteosarcoma and are most often utilized in patients with advanced unresectable disease.”
§ Osteosarcoma > Relapsed osteosarcoma
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“One of the life-threatening late effects of chemotherapy is the development of secondary malignancies, such as therapy-related acute myelogenous leukaemia/myelodysplastic syndrome, central nervous system tumours or secondary solid tumours, which occur in ~3% of patients 125 .”
§ Osteosarcoma > Late effects
What the sources say
- Not checked yetcites [125] Smeland, S. et al. Survival and prognosis with osteosarcoma: outcomes in more than 2000 patients in the EURAMOS-1 (European and American Osteosarcoma Study) cohort. Eur. J. Cancer 109, 36–50 (2019). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Allogeneic heart transplants may be indicated for severe cases 165,166 .”
§ Osteosarcoma > Late effects
What the sources say
- Not checked yetcites [165] Bock, M. J. et al. Cancer recurrence and mortality after pediatric heart transplantation for anthracycline cardiomyopathy: a report from the Pediatric Heart Transplant Study (PHTS) group. Pediatr. Transpl. https://doi.org/10.1111/petr.12923 (2017). source
- Not checked yetcites [166] Shugh, S. B. & Ryan, T. D. Heart transplantation in survivors of childhood cancer. Transl Pediatr. 8, 314–321 (2019). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“For comparison, a 4-month PFS of 0% in the control arm of the phase II trials of regorafenib and of 15% for a historical benchmark established by a pooled analysis of 96 patients with osteosarcoma and measurable disease enrolled on seven Children's Oncology Group phase II trials were observed 152 .”
§ Osteosarcoma > Relapsed osteosarcoma
What the sources say
- Not checked yetcites [152] Lagmay, J. P. et al. Outcome of patients with recurrent osteosarcoma enrolled in seven phase II trials through Children’s Cancer Group, Pediatric Oncology Group, and Children’s Oncology Group: learning from the past to move forward. J. Clin. Oncol. 34, 3031–3038 (2016). source
plainn = 96- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Prospective clinical trials evaluated the MTKIs sorafenib, regorafenib, cabozantinib, lenvatinib and apatinib as single agents in patients with relapsed or refractory osteosarcoma, with most enrolled patients falling in the adult age range 146,147,148,149,150,151 (Table 2).”
§ Osteosarcoma > Relapsed osteosarcoma
What the sources say
- Not checked yetcites [146] Davis, L. E. et al. Randomized double-blind phase II study of regorafenib in patients with metastatic osteosarcoma. J. Clin. Oncol. 37, 1424–1431 (2019). source
- Not checked yetcites [147] Grignani, G. et al. A phase II trial of sorafenib in relapsed and unresectable high-grade osteosarcoma after failure of standard multimodal therapy: an Italian Sarcoma Group study. Ann. Oncol. 23, 508–516 (2012). source
- Not checked yetcites [148] Italiano, A. et al. Cabozantinib in patients with advanced Ewing sarcoma or osteosarcoma (CABONE): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 21, 446–455 (2020). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Other secondary leukaemias are often myelomonoblastic and their lag-time is shorter; these develop after exposure to topoisomerase II inhibitors, including anthracyclines such as doxorubicin.”
§ Osteosarcoma > Late effects
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Curative osteosarcoma treatment, including anthracyclines, alkylating agents and/or topoisomerase II inhibitors, is known to cause secondary malignancies and the risk is likely increased by individual cancer predisposition and other as yet unidentified factors 155,157 .”
§ Osteosarcoma > Late effects
What the sources say
- Not checked yetcites [155] Hecker-Nolting, S., Langer, T., Blattmann, C., Kager, L. & Bielack, S. S. Current insights into the management of late chemotherapy toxicities in pediatric osteosarcoma patients. Cancer Manag. Res. 13, 8989–8998 (2021). source
- Not checked yetcites [157] Kratz, C. P. et al. Predisposition to cancer in children and adolescents. Lancet Child Adolesc. Health 5, 142–154 (2021). source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Several chemotherapy regimens are recommended by the National Cancer Care Network (NCCN) and European Society of Medical Oncology (ESMO) guidelines at the time of osteosarcoma recurrence 104,141 .”
§ Osteosarcoma > Relapsed osteosarcoma
What the sources say
- Not checked yetcites [104] Strauss, S. J. et al. Bone sarcomas: ESMO-EURACAN-GENTURIS-ERN PaedCan Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann. Oncol. 32, 1520–1536 (2021). source
- Not checked yetcites [141] NCCN. Treatment by cancer type. NCCN https://www.nccn.org/guidelines/category_1 (2022).
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The renal glomerulus might be affected by cisplatin treatment in 60-80% of children and adolescents and renal tubular function is affected by ifosfamide treatment in 20-25% 171 .”
§ Osteosarcoma > Late effects
What the sources say
- Not checked yetcites [171] Skinner, R. Late renal toxicity of treatment for childhood malignancy: risk factors, long-term outcomes, and surveillance. Pediatr. Nephrol. 33, 215–225 (2018). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“An increased risk of herpes zoster infection has been found in those individuals and administration of prophylaxis is recommended for patients at risk 174 .”
§ Osteosarcoma > Late effects
What the sources say
- Not checked yetcites [174] Bader, M. S. Herpes zoster: diagnostic, therapeutic, and preventive approaches. Postgrad. Med. 125, 78–91 (2013). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Multi-target tyrosine kinase inhibitors (TKIs) have demonstrated activity in phase II clinical trials and may offer benefit in this setting.”
§ Osteosarcoma > Clinical research
boostedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In this group of patients, the burden of physical health conditions was high, with 32% of osteosarcoma survivors self-reporting impaired physical functioning and 16% reporting impaired general health, which is considerably worse than in matched controls.”
§ Osteosarcoma > Quality of life
What the sources say
- Not checked yetcites [178] Edelmann, M. N. et al. Neurocognitive and patient-reported outcomes in adult survivors of childhood osteosarcoma. JAMA Oncol. 2, 201–208 (2016). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Inner ear damage and permanent hearing loss is a possible incapacitating late chemotherapy effect of cisplatin use, with moderate to severe hearing loss occurring in <30% of patients with osteosarcoma 168 .”
§ Osteosarcoma > Late effects
What the sources say
- Not checked yetcites [168] Moke, D. J. et al. Prevalence and risk factors for cisplatin-induced hearing loss in children, adolescents, and young adults: a multi-institutional North American cohort study. Lancet Child Adolesc. Health 5, 274–283 (2021). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Well-established cell lines, such as SaOS, MG63, KHOS, MNNG-HOS, U2OS and OS-17, have facilitated investigation into mechanisms of malignancy 206,207 and high-throughput screens to identify osteosarcoma vulnerabilities 92,208 .”
§ Osteosarcoma > Box 1 : Box 1 Relevant osteosarcoma disease models Cell lines
What the sources say
- Not checked yetcites [206] Ségaliny, A. I. et al. Interleukin-34 promotes tumor progression and metastatic process in osteosarcoma through induction of angiogenesis and macrophage recruitment. Int. J. Cancer 137, 73–85 (2015). source
- Not checked yetcites [207] Ory, B. et al. Zoledronic acid suppresses lung metastases and prolongs overall survival of osteosarcoma‐bearing mice. Cancer 104, 2522–2529 (2005). source
- Not checked yetcites [92] Bayles, I. et al. Ex vivo screen identifies CDK12 as a metastatic vulnerability in osteosarcoma. J. Clin. Invest. 129, 4377–4392 (2019). source
- Not checked yetcites [208] Dharia, N. V. et al. A first-generation pediatric cancer dependency map. Nat. Genet. 53, 529–538 (2021). source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Inhibitors of DNA damage repair include inhibitors of WEE1, PARP and ATR.”
§ Osteosarcoma > Clinical research
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“Cisplatin-induced glomerular effects are rarely severe enough to require treatment but ifosfamide-induced renal tubular effects can lead to clinically relevant electrolyte wasting in the form of Fanconi syndrome 171 .”
§ Osteosarcoma > Late effects
What the sources say
- Not checked yetcites [171] Skinner, R. Late renal toxicity of treatment for childhood malignancy: risk factors, long-term outcomes, and surveillance. Pediatr. Nephrol. 33, 215–225 (2018). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Due to the loosening of FDA restrictions, many of these trials are now also available for patients aged ≥12 years, which includes most patients with osteosarcoma 192 .”
§ Osteosarcoma > Clinical research
What the sources say
- Not checked yetcites [192] FDA. Considerations for the inclusion of adolescent patients in adult oncology clinical trials: guidance for industry. FDA https://bit.ly/2IMiAdT (2019).
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A single institution study evaluating HRQoL in 80 survivors at least 10 years after the initial diagnosis of osteosarcoma revealed that individuals had neurocognitive impairment, with significantly lower mean scores in reading skills (P = 0.01), sustained attention (P = 0.002), short-term memory (P = 0.01) and physical processing speed (P < 0.001) compared with matched controls 178 .”
§ Osteosarcoma > Quality of life
What the sources say
- Not checked yetcites [178] Edelmann, M. N. et al. Neurocognitive and patient-reported outcomes in adult survivors of childhood osteosarcoma. JAMA Oncol. 2, 201–208 (2016). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A high proportion of osteosarcoma samples have an increased number of tumour-infiltrating lymphocytes, suggesting immune system activation in many patients with osteosarcoma 180 .”
§ Osteosarcoma > Basic research
What the sources say
- Not checked yetcites [180] Koirala, P. et al. Immune infiltration and PD-L1 expression in the tumor microenvironment are prognostic in osteosarcoma. Sci. Rep. 6, 30093 (2016). source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“setting is not well defined but may offer palliative benefit for those with unresectable or systemic relapse.”
§ Osteosarcoma > Clinical research
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“Generally, fertility is most impaired by alkylators and more so in males than in females 175 .”
§ Osteosarcoma > Late effects
What the sources say
- Not checked yetcites [175] van Santen, H. M. et al. Reproductive complications in childhood cancer survivors. Pediatr. Clin. North Am. 67, 1187–1202 (2020). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Surface targets for the following proteins include HER2: Antibody, ADC, CAR T; GD2: Antibody, CAR T; B7H3: CAR T; EGFR: CAR T.”
§ Osteosarcoma > Clinical research
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Patients with unresectable and/or widely metastatic disease may receive palliative chemotherapy and/or radiotherapy.”
§ Osteosarcoma > Comparative studies
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Osteosarcoma can present in any bone in the body but the most common sites are around the knee and the proximal humerus 201 .”
§ Osteosarcoma > Comparative studies
What the sources say
- Not checked yetcites [201] Meyers, P. A. & Gorlick, R. Osteosarcoma. Pediatr. Clin. North. Am. 44, 973–989 (1997). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Canine osteosarcoma has histological, genetic and clinical features nearly identical to the human disease 232 but has a much higher incidence, with an estimated 25,000 new cases of canine disease occurring each year 232 .”
§ Osteosarcoma > Comparative studies
What the sources say
- Not checked yetcites [232] Gardner, H. L. et al. Canine osteosarcoma genome sequencing identifies recurrent mutations in DMD and the histone methyltransferase gene SETD2. Commun. Biol. 2, 266 (2019). source
hedgedn = 25,000- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Osteosarcoma (OS) cells become progressively oligoclonal or polyclonal and form a highly heterogeneous tumour mass.”
§ Osteosarcoma > Comparative studies
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Although prolonged passage in mice can alter the behaviour of tumours maintained as PDXs 227 , strategic use of low-passage PDX lines limits this mouse-specific evolution and is a useful tool in the study of osteosarcoma biology 228 , precision medicine approaches and preclinical validation of therapeutic candidates.”
§ Osteosarcoma > Primary and PDX-derived cultures
What the sources say
- Not checked yetcites [227] Ben-David, U. et al. Patient-derived xenografts undergo mouse-specific tumor evolution. Nat. Genet. 49, 1567–1575 (2017). source
- Not checked yetcites [228] Woo, X. Y. et al. Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts. Nat. Genet. 53, 86–99 (2021). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Interaction between cancer and bone cells leads to an increase in OS cell proliferation and altered bone remodelling.”
§ Osteosarcoma > Comparative studies
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Patients with resectable high-grade osteosarcoma require chemotherapy and resection of all sites of disease.”
§ Osteosarcoma > Comparative studies
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“These techniques have been adapted to study tumour-host interactions, to screen for metastasis-related vulnerabilities and to validate hits identified in other screens 74,75,92,216,217,218,219 .”
§ Osteosarcoma > Ex vivo organ cultures
What the sources say
- Not checked yetcites [74] Ren, L. et al. Dysregulation of Ezrin phosphorylation prevents metastasis and alters cellular metabolism in osteosarcoma. Cancer Res. 72, 1001–1012 (2012). source
- Not checked yetcites [75] Morrow, J. J. et al. Positively selected enhancer elements endow osteosarcoma cells with metastatic competence. Nat. Med. 24, 176–185 (2018). source
- Not checked yetcites [92] Bayles, I. et al. Ex vivo screen identifies CDK12 as a metastatic vulnerability in osteosarcoma. J. Clin. Invest. 129, 4377–4392 (2019). source
- Not checked yetcites [216] Tsai, Y. C. et al. The ubiquitin ligase gp78 promotes sarcoma metastasis by targeting KAI1 for degradation. Nat. Med. 13, 1504–1509 (2007). source
- Not checked yetcites [217] Lizardo, M. M. et al. Upregulation of glucose-regulated protein 78 in metastatic cancer cells is necessary for lung metastasis progression. Neoplasia 18, 699–710 (2016). source
- Not checked yetcites [218] Morrow, J. J. et al. mTOR inhibition mitigates enhanced mRNA translation associated with the metastatic phenotype of osteosarcoma cells in vivo. Clin. Cancer Res. 22, 6129–6141 (2016). source
- Not checked yetcites [219] Yu, P. Y. et al. Target specificity, in vivo pharmacokinetics, and efficacy of the putative STAT3 inhibitor LY5 in osteosarcoma, Ewing’s sarcoma, and rhabdomyosarcoma. PLoS ONE 12, e0181885 (2017). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In addition, OS cells activate local mesenchymal stem cells (MSCs) by producing extracellular vesicles (EVs) containing TGFβ, which in turn release EVs containing IL-6, facilitating tumour progression.”
§ Osteosarcoma > Comparative studies
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Similarly, cytokine-containing EVs prepare the lung metastatic niche to receive OS circulating tumour cells.”
§ Osteosarcoma > Comparative studies
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“Canine companion animals that develop sporadic osteosarcoma present a unique opportunity to study tumour biology and therapy in ways that can accelerate discovery and benefit both species 231 .”
§ Osteosarcoma > Comparative studies
What the sources say
- Not checked yetcites [231] Fenger, J. M., London, C. A. & Kisseberth, W. C. Canine osteosarcoma: a naturally occurring disease to inform pediatric oncology. ILAR J. 55, 69–85 (2014). source
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Both neoadjuvant and adjuvant chemotherapy is usually given but surgery may be considered upfront followed by adjuvant chemotherapy in selected cases.”
§ Osteosarcoma > Comparative studies
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Low-grade and intermediate-grade osteosarcomas are managed with surgery alone.”
§ Osteosarcoma > Comparative studies
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In the metastatic foci, cytokines and growth factors contribute to the local tumour development and EVs seem to be the main messenger between OS cells and the pulmonary parenchyma.”
§ Osteosarcoma > Comparative studies
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The authors state this as an assumption.
Osteosarcoma arises from a multipotent mesenchymal precursor.
“This microscopic phenotype has long fuelled the assumption that osteosarcoma arises from a multipotent mesenchymal precursor.”
The paper relies on this without support.
Population-based screening and surveillance strategies for osteosarcoma have not been implemented because the disease is rare and reliable markers are lacking.
“So far, population-based screening and surveillance strategies have not been implemented due to the rarity of osteosarcoma and the lack of reliable markers.”
The paper relies on this without support.
Osteosarcoma lesions are heterogeneous and diagnostic features such as malignant osteoid vary from sample to sample.
“For core needle biopsies, adequate sampling of the tissue has to be ensured as osteosarcoma lesions can be quite heterogeneous and diagnostic features (such as malignant osteoid) can vary from sample to sample.”
The paper relies on this without support.
Fine-needle aspirates lack sufficient histological context and make tumour grade assessment difficult.
“Fine-needle aspirates are usually inadequate for a definitive diagnosis of osteosarcoma due to the lack of sufficient histological context and the resulting difficulty to assess tumour grade, and are therefore not recommended.”
The paper relies on this without support.
Most osteosarcoma patients present with high-grade lesions that have both bony and soft tissue components.
“Most patients present with high-grade lesions that have both bony and soft tissue components, making the presence or absence of metastasis the primary risk-stratifying feature at diagnosis.”
The paper relies on this without support.
Combination chemotherapy and complete surgical resection are essential for cure in osteosarcoma.
“Combination chemotherapy and complete surgical resection are essential for cure.”
The paper relies on this without support.
Osteosarcoma is radio-resistant.
“Although osteosarcoma is regarded as a radio-resistant disease, radiotherapy as local control may be considered if resection of a primary tumour is not possible or anticipated to lead to unacceptable morbidities such as in pelvic, trunk or craniofacial primary sites of disease 104 .”
The paper relies on this without support.
Outcomes for osteosarcoma have hardly improved in the past decades.
“However, outcomes have hardly improved in the past decades, and the intensive chemotherapy regimens used are associated with important acute and long-term toxic effects and considerable impact on quality of life.”
The paper relies on this without support.
Data on lower-grade osteosarcoma lesion management remain sparse.
“Data on lower-grade lesion management remain sparse; however, most clinicians agree that grade 1 localized parosteal tumours can be treated surgically.”
The paper relies on this without support.
The general principle of treating osteosarcoma subvariants is based on their grade.
“The general principle of treating subvariants in osteosarcoma is based on their grade.”
The paper relies on this without support.
Immune cell infiltration occurs in osteosarcoma.
“based on the immune cell infiltration known to occur in osteosarcoma”
The paper relies on this without support.
Data from new agents are strictly controlled by trial sponsors, preventing their application to increase understanding of the disease.
“In addition, because these are new agents, the data is strictly controlled by trial sponsors, which prevents their application to increase understanding of the disease.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Outcomes remain poor for children and young adults with advanced solid tumors.1–5”
From Clinical Liquid Biopsy Testing for Detection of Actionable Genomic Alterations in Children and Young Adults With Advanced Solid Tumors on the GAIN Study (2026) · cites this paper as [4]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Osteosarcoma > Comparative studies
“Regorafenib (REGOBONE) 26 (regorafenib) 12 (placebo) 2 (8%) 0 (0%) 16.4 (8-27) 4.1 (3-15.7)0.46 (28-63%) 0%”
§ Osteosarcoma > Comparative studies
“Median PFS, months (95% CI) 4-month PFS (95% CI)”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
“Lenvatinib 26 2 (7%)”
§ Osteosarcoma > Comparative studies
Reported 7 · recomputed 7.692308
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Osteosarcoma > Relapsed osteosarcoma
“Four-month progression-free survival (PFS) ranged from 35% to 70% 146,147,148,149,151 .”
§ Osteosarcoma > Comparative studies
“Lenvatinib 26 2 (7%) 3 (1.8-5.4)0.29 (14-48%) 10 (5.6-12.3)160 Cabozantinib 42 5 (12%) 6.7 (5.4-7.9)0.71 (55-83%) 10.6 (7.4-12.5)158”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Osteosarcoma > Relapsed osteosarcoma
“Objective response rates were low at 10-15%.”
§ Osteosarcoma > Comparative studies
“Apatinib 37 16 (43%)”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Osteosarcoma > Clinical research
“In these trials, MTKIs were effective in reducing PFS, becoming the mainstay of treatments for patients with relapsed disease.”
§ Osteosarcoma > Relapsed osteosarcoma
“For comparison, a 4-month PFS of 0% in the control arm of the phase II trials of regorafenib and of 15% for a historical benchmark established by a pooled analysis of 96 patients with osteosarcoma and measurable disease enrolled on seven Children's Oncology Group phase II trials were observed 152 .”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
“Sorafenib 35 3 (8%)”
§ Osteosarcoma > Comparative studies
Reported 8 · recomputed 8.571429
Citations
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Self-citationAging reshapes the osteosarcoma ecosystem through immune dysfunction and tumor cell reprogramming
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Self-citation
Metadata
- Authors
- Beird, H. C., Bielack, S. S., Flanagan, A. M., Gill, J., Heymann, D., Janeway, K. A., Livingston, J. A., Roberts, R. D., Strauss, S. J., & Gorlick, R.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Olgahospital (DE)
- University College London (GB)
- Centre National de la Recherche Scientifique (FR)
- Harvard University (US)
- Nationwide Children's Hospital (US)
- University College London Hospitals NHS Foundation Trust (GB)
- ORCID
- Venue
- Nature Reviews Disease Primers
- Published
- 2022-12-08
- Volume
- 8
- Issue
- 1
- Pages
- 77-77
- ISSN
- 2056-676X (ISSN-L)
- OpenAlex
- W4313366903
- Semantic Scholar
- a45c4839de5d7b9e2366faa7f8f0cee9e842f5ac
- Cited by
- 660
- References
- 218
- Citations by year
- 2026: 203 · 2025: 220 · 2024: 174 · 2023: 63
- FWCI
- 19.81
- Type
- journal article
- Language
- en
- Update notices
- correction (2022-12-30)
- Open access
- green
- inserm.hal.science
- Licence
- Locations
- Nature Reviews Disease Primers (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, public-domain)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Cancer Research UK
- National Institute for Health and Care Research
- Agence Nationale de la Recherche (ANR-10-SATT-0008)
- Topics
- Health Sciences › Medicine › Oncology › Sarcoma Diagnosis and Treatment
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone Tumor Diagnosis and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac tumors and thrombi
- Keywords
- osteosarcoma, primary bone malignancy, incidence, pathogenesis, bone formation, metastasis, lung metastasis, radiographic diagnosis, bone biopsy, multidisciplinary management, late effects, quality of life
- MeSH terms
- Bone Neoplasms, Child, Humans, Quality of Life, Osteosarcoma
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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