The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma
Open accessAbstract
BACKGROUND: Glioblastoma, the most common primary brain tumor in adults, is usually rapidly fatal. The current standard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible, followed by adjuvant radiotherapy. In this trial we compared radiotherapy alone with radiotherapy plus temozolomide, given concomitantly with and after radiotherapy, in terms of efficacy and safety. METHODS: Patients with newly diagnosed, histologically confirmed glioblastoma were randomly assigned to receive radiotherapy alone (fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy) or radiotherapy plus continuous daily temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle). The primary end point was overall survival. RESULTS: A total of 573 patients from 85 centers underwent randomization. The median age was 56 years, and 84 percent of patients had undergone debulking surgery. At a median follow-up of 28 months, the median survival was 14.6 months with radiotherapy plus temozolomide and 12.1 months with radiotherapy alone. The unadjusted hazard ratio for death in the radiotherapy-plus-temozolomide group was 0.63 (95 percent confidence interval, 0.52 to 0.75; P<0.001 by the log-rank test). The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiotherapy alone. Concomitant treatment with radiotherapy plus temozolomide resulted in grade 3 or 4 hematologic toxic effects in 7 percent of patients. CONCLUSIONS: The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma resulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity.
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In the citing paper
“The standard treatment for high-grade gliomas such as glioblastoma (grade IV) is surgery followed by chemotherapy and radiation therapy [45].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [45]
Experimental — accuracy not yet measuredIn the citing paper
“Since the current clinically actionable sub-compartments are TC (i.e., considered for surgery) and WT (i.e., considered for radiotherapy)42, performance improvements of their boundary detection may contribute to the model’s clinical impact and relevance.”
From Federated learning enables big data for rare cancer boundary detection (2022) · cites this paper as [42]
In the citing paper
“Stupp et al. originally reported that treatment of patients with GBM with TMZ and radiation resulted in an approximately 20% increase in progression-free survival compared with radiation therapy alone.39”
From Combination therapy in a xenograft model of glioblastoma: Enhancement of the antitumor activity of temozolomide by an MDM2 antagonist (2017) · cites this paper as [39]
In the citing paper
“An effect size of 20% increase in survival was considered to be biologically significant when comparing survival in TMZ versus combination T/N-treated mice.39”
From Combination therapy in a xenograft model of glioblastoma: Enhancement of the antitumor activity of temozolomide by an MDM2 antagonist (2017) · cites this paper as [39]
In the citing paper
“An increase of median survival of 13.4 months for patients treated with a combination of MFH and radiotherapy after glioblastoma recurrence was obtained (Figure 7E). As compared to the abovementioned historical control group, where the median survival after recurrence was 6.2 months, this increase is substantial.”
From Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications (2019) · cites this paper as [223]
In the citing paper
“An increase of median survival of 13.4 months for patients treated with a combination of MFH and radiotherapy after glioblastoma recurrence was obtained (Figure 7E). As compared to the abovementioned historical control group, where the median survival after recurrence was 6.2 months, this increase is substantial.”
From Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications (2019) · cites this paper as [224]
In the citing paper
“It is highly unlikely that this additional technical support would translate into a 3-month prolongation of median survival, which is in the range of the benefit seen with the introduction of TMZ.26”
From Tumor treating fields: A novel treatment modality and its use in brain tumors (2016) · cites this paper as [26]
In the citing paper
“However, a strong selection bias and inclusion of patients with pseudoprogression after initial TMZ chemoradiotherapy cannot be ruled out in this uncontrolled routine practice patient population.26”
From Tumor treating fields: A novel treatment modality and its use in brain tumors (2016) · cites this paper as [26]
In the citing paper
“In the PriDE dataset reflecting routine clinical use of the device, patients who received TTFields at first recurrence were treated for a median of 6.2 months and had a median survival of 20 months, comparing favorably with recent trial results investigating other novel agents.”
From Tumor treating fields: A novel treatment modality and its use in brain tumors (2016) · cites this paper as [26]
In the citing paper
“while the published Temozolomide data indicates an increase of about 20% in OS compared to ionizing radiation treatment alone [14]”
From Chemotherapeutic treatment efficacy and sensitivity are increased by adjuvant alternating electric fields (TTFields) (2009) · cites this paper as [14]
In the citing paper
“However, if we assume that the TTFields therapeutic efficacy for newly diagnosed patients is similar to recurrent GBM, i.e. the median of OS is increased by 270% [1] while the published Temozolomide data indicates an increase of about 20% in OS compared to ionizing radiation treatment alone [14], the results presented in Figure 6 point towards additivity between TTFields and Temozolomide.”
From Chemotherapeutic treatment efficacy and sensitivity are increased by adjuvant alternating electric fields (TTFields) (2009) · cites this paper as [14]
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Metadata
- Authors
- Stupp, R., Mason, W. P., van den Bent, M. J., Weller, M., Fisher, B., Taphoorn, M. J. B., Belanger, K., Brandes, A. A., Marosi, C., Bogdahn, U., Curschmann, J., Janzer, R. C., Ludwin, S. K., Gorlia, T., Allgeier, A., Lacombe, D., Cairncross, J. G., Eisenhauer, E., & Mirimanoff, R. O.
- Affiliations
- Centre Hospitalier Universitaire Vaudois (CH)
- Princess Margaret Cancer Centre (CA)
- University of Tübingen (DE)
- Western University (CA)
- University Medical Center Utrecht (NL)
- Azienda Ospedale - Università Padova (IT)
- Medical University of Vienna (AT)
- University Hospital Regensburg (DE)
- University Hospital of Bern (CH)
- Queen's University (CA)
- European Organisation for Research and Treatment of Cancer (NL)
- University of Calgary (CA)
- Canadian Cancer Trials Group (CA)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2005-03-10
- Volume
- 352
- Issue
- 10
- Pages
- 987-996
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2096287682
- Cited by
- 21,807
- References
- 35
- Citations by year
- 2026: 1259 · 2025: 1369 · 2024: 1444 · 2023: 1500 · 2022: 1532 · 2021: 1614 · 2020: 1453 · 2019: 1256 · 2018: 1167 · 2017: 1156 · 2016: 1068 · 2015: 1110 · 2014: 1019 · 2013: 901 · 2012: 872
- FWCI
- 171.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- CRC Press eBooks (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion, other-oa)
- Funders
- National Cancer Institute (5U10-CA11488-30, 5U10-CA11488-32, 5U10-CA11488-33, 5U10-CA11488-31, U10CA011488, 5U10 CA11488-34)
- Topics
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Health Sciences › Medicine › Oncology › Brain Metastases and Treatment
- Keywords
- glioblastoma, temozolomide, radiotherapy, concurrent chemoradiotherapy, adjuvant chemotherapy, overall survival, hematologic toxicity, newly diagnosed brain tumors
- MeSH terms
- Temozolomide, Adrenal Cortex Hormones, Adult, Aged, Brain Neoplasms, Dacarbazine, Female, Glioblastoma, Humans, Male, Middle Aged, Radiotherapy, Computer-Assisted, Proportional Hazards Models, Survival Analysis, Chemotherapy, Adjuvant, Disease Progression, Antineoplastic Agents, Alkylating
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