Stereotactic ablative radiotherapy: a potentially curable approach to early stage multiple primary lung cancer
Open accessAbstract
BACKGROUND: Surgical resection has been the standard treatment for early stage multiple primary lung cancer (MPLC). However, a significant proportion of patients with MPLC cannot undergo surgery. For this report, the authors explored the role of stereotactic ablative radiotherapy (SABR) for patients with MPLC. METHODS: Patients with MPLC who received SABR (50 grays [Gy] in 4 fractions or 70 Gy in 10 fractions) for the second tumor were reviewed. Four-dimensional, computed tomography-based, planning/volumetric image-guided treatment was used for all patients. Treatment outcomes/toxicities were analyzed. RESULTS: For the 101 patients who received SABR, at a median follow-up of 36 months and with a median overall survival (OS) of 46 months, the 2-year and 4-year in-field local control rates were 97.4% and 95.7%, respectively. The 2-year and 4-year OS rates were 73.2% and 47.5%, respectively; and the progression-free survival (PFS) rates were 67% and 58%, respectively. Patients who had metachronous tumors had better OS and PFS than patients who had synchronous tumors (2-year OS: 80.6% metachronous vs 61.5% synchronous; 4-year OS: 52.7% vs 39.7%, respectively; P = .047; 2-year PFS: 84.7% vs 49.4%, respectively; 4-year PFS: 75.6% vs 30.4%, respectively; P = .0001). For patients who either underwent surgery or received SABR for an index tumor, the incidence of grade ≥ 3 radiation pneumonitis was 3% (2 of 71 patients); however, this increased to 17% (5 of 30 patients) for those who received conventional radiotherapy for an index tumor. Other grade ≥ 3 toxicities included grade 3 chest wall pain (3 of 101 patients; 3%) and grade 3 skin toxicity (1 of 101 patients; 1%). CONCLUSIONS: SABR achieves promising long-term tumor control and survival and may be a potential curative treatment for early stage MPLC.
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Surgery and stereotactic radiosurgery have been shown to produce long-term survivors in patients with a solitary lesion in the contralateral lung.
“Both surgery [169, 170] and SRS [171, 172] have been shown to result in long-term survivors in this setting [IV, B].”
From Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2016) · cites this paper as [172]
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Optimizing SABR delivery for synchronous multiple lung tumors using volumetric-modulated arc therapy
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Background1-, 3-, and 5-year survival among early-stage lung cancer patients treated with lobectomy vs SBRT
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“In one study of 58 operable, stage I NSCLC patients (31 SABR, 27 surgery), the 3-year survival outcomes were found to be superior in the SABR group compared to those undergoing lobectomy (95% vs 79%, respectively).(9) Surgical resection, however, resulted in significantly improved outcomes in several other investigati…”
Dong, B., Chen, R., Zhu, X., Wu, Q., Jin, J., Wang, W., Zhu, Y., Jiang, H., Bi, N., Wang, X., et al. (2023) · Clinical and Translational Radiation Oncology · doi:10.1016/j.ctro.2023.100601 · Cited by 13 · see citing works
“However, the feasibility and safety of SBRT in the MPLC patients who already underwent lung resection have not been clearly established [15,16].”
BackgroundResultMultidisciplinary expert consensus on diagnosis and treatment of multiple lung cancers
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“Curative treatments, such as surgical resection or stereotactic ablative radiotherapy, have their limitation (3,4).”
BackgroundDiagnosis and management of multiple primary lung cancer
Dong, H., Tian, Y., Xin, S., Jiang, S., Guo, Y., Wan, Z., & Han, Y. P. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1392969 · Cited by 12 · see citing works
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“(12) analyzed clinical outcomes of 101 patients withMPLC treated with SBRT, 47 of whom had undergone operation for the index lung cancer.”
BackgroundAoki, S., Yamashita, H., Takahashi, W., Nawa, K., Ota, T., Imae, T., Ozaki, S., Nozawa, Y., Nakajima, J., Sato, M., et al. (2020) · Oncology Letters · doi:10.3892/ol.2020.11407 · Cited by 12 · see citing works
“Even for patients in which operative treatment would be viable, SBRT has previously achieved results similar to those of surgery (29-31), and an increasing number of studies have reported the expansion of factors that may indicate the Salvage stereotactic body radiotherapy for post‐operative oligo‐recurrence of non‐sm…”
ResultStereotactic body radiotherapy for synchronous early stage non-small cell lung cancer
Steber, C. R., Hughes, R. T., Soike, M. H., Helis, C. A., Nieto, K., Jacobson, T., Nagatsuka, M., McGinnis, H. S., Leyrer, C. M., & Farris, M. K. (2021) · Acta Oncologica · doi:10.1080/0284186x.2021.1892182 · Cited by 11 · see citing works
“The current study evaluates disease control and survival outcomes after SBRT was delivered as definitive treatment to all SPLC lesions, which is somewhat unique amongst the sparse literature reporting on SPLC management [11,14,15,21].”
MethodResultInfluentialSecond Primary Lung Cancers Demonstrate Better Survival with Surgery than Radiation
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“5% and 4-year survival rate of 39% with stereotactic ablative radiotherapy (SABR) in early stage multiple synchronous lung cancers with contraindications to surgical resection [17].”
BackgroundGenetic trajectory and clonal evolution of multiple primary lung cancer with lymph node metastasis
Tian, H., Wang, Y., Yang, Z., Chen, P., Xu, J., Tian, Y., Fan, T. T., Xiao, C., Bai, G., Li, L., et al. (2023) · Cancer Gene Therapy · doi:10.1038/s41417-022-00572-0 · Cited by 9 · see citing works
“However, many therapies are feasible in MPLC, including photodynamic therapy [55], stereotactic ablative radiotherapy [56], and a combination of local radiofrequency ablation and melatonin [57].”
BackgroundIshihara, T., Yamada, K., Harada, A., Yukiue, H., Tanahashi, M., Niwa, H., Matsui, T., Yokomura, K., Ejima, Y., & Sasaki, R. (2018) · Acta Oncologica · doi:10.1080/0284186x.2018.1468088 · Cited by 9 · see citing works
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Multiple Primary Lung Cancers: Treatment Outcomes After Stereotactic Body Radiotherapy (SBRT)
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“Previous retrospective studies have reported the outcome of MPLC treated with SBRT alone, or in combination with other methods [4-9].”
BackgroundResultHypofractionated radiotherapy for medically inoperable stage I non‐small cell lung cancer
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Practical considerations of single-fraction stereotactic ablative radiotherapy to the lung
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“An earlier analysis of MPLC included 39 patients with synchronous and 62 with metachronous tumors and found that the latter had better OS and PFS [12].”
BackgroundMethodJin, C. J., Mei, X., & Falkson, C. B. (2016) · BJR|case reports · doi:10.1259/bjrcr.20150464 · Cited by 5 · see citing works
“For early-stage multiple primary lung cancers, there is limited evidence suggesting comparable outcomes with SABR and surgery.(6) Tangential WBI with RNI was deemed appropriate for our patient's breast cancer.”
ResultLadbury, C. J., Sidiqi, B. U., Cantrell, N., Jones, G. P., Skalina, K. A., Fekrmandi, F., Andraos, T. Y., Gogineni, E., Dolan, J. L., Siva, S., et al. (2024) · Practical Radiation Oncology · doi:10.1016/j.prro.2024.09.012 · Cited by 4 · see citing works
[Advances in Diagnosis and Treatment of Multiple Primary Lung Cancer].
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Stereotactic body radiation therapy for pulmonary large cell neuroendocrine carcinoma: a case report
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“In the LCNEC context, a few SBRT studies on early stage NSCLC patients included cases with LCNEC histology, but the treatment outcomes were not separately described.(23) To the best of our knowledge, our present study is the first to report the outcomes of SBRT in an LCNEC patient.”
Evolution of Stereotactic Ablative Radiotherapy in Lung Cancer and Birmingham’s (UK) Experience
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Progress in genome-inspired treatment decisions for multifocal lung adenocarcinoma
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“The interval between the two lesions was defined as the time between the date of surgery for the first tumor and the date of radiological diagnosis of the de novo pulmonary lesion.(17,23) This retrospective study was approved by the Zhongshan Hospital Ethics Committee.”
BackgroundMethodResultLiu, Y., Han, Y., Dong, Y., & Zhang, D. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1062138 · Cited by 2 · see citing works
Focus on Recommendations for the Management of Non-small Cell Lung Cancer
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Stereotactic ablative radiation therapy in lung cancer
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“…radiotherapy (SABR) is the preferred alternative for those who are not fit for surgical resection and have similar outcomes in survival compared with surgical resection, and have also reported greater local tumor control and overall survival compared with conventional radiation therapy [13 , 14] .”
ResultLong-Term Survival and CANARY-Based Artificial Intelligence for Multifocal Lung Adenocarcinoma
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Synchronous primary lung cancers in a 51-year-old woman - a case report and literature review
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Stereotactic Ablative Radiotherapy for Lung Cancer
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Synchronous primary lung cancers in a 51-year-old woman – a and literature review
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BackgroundMethodInfluentialRole of interferons and immunotherapy in enhancing radiation treatment of cancer
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Indicaciones terapéuticas y paliativas de la cirugía en los tumores pulmonares y torácicos
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Multiple pulmonary ground-glass nodules: Challenges and advances
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“[124] Chang et al [125] reported that the 2-and 4-year local control rates of SBRT for MPLC were 97.4% and 95.7%, respectively; the 2-and 4-year OS rates were 73.2% and 47.5%, respectively, and the progression-free survival rates were 67.0% and 58.0%, respectively.”
BackgroundInfluentialMa, J., Xu, X., Huang, W., Hu, Y. S., Chen, G., & He, J. (2025) · BMC Cancer · doi:10.1186/s12885-025-13540-2
“The results demonstrated that SBRT achieved excellent LC rates and improved prognosis [12].”
A Case Report of Multiple Primary Lung Cancer and Literature Review
李, 兵. (2026) · Advances in Clinical Medicine · doi:10.12677/acm.2026.1641297
Multiple primary lung cancers, the hybrid approach in management: a case report
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“In addition, the progression-free survival was significantly higher in MMPLCs than in SMPLCs [22, 23].”
InfluentialMultiple ground-glass nodules after lobectomy for multiple primary lung cancer: a case report
Song, Z., Huang, S., Wang, Z., Zhang, Q., & Zhang, X. L. (2026) · Frontiers in Surgery · doi:10.3389/fsurg.2026.1842030
“SBRT has been recommended by the NCCN Guidelines as a standard therapeutic modality for unresectable early-stage lung cancer, and its clinical application in MPLC is gradually expanding (22).”
- Authors
- Chang, J. Y., Liu, Y., Zhu, Z., Welsh, J. W., Gomez, D. R., Komaki, R., Roth, J. A., & Swisher, S. G.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Department of Radiation Oncology The University of Texas MD Anderson Cancer Center Houston Texas
- Corresponding author
- Chang, Joe Y.
- ORCID
- Venue
- Cancer
- Publisher
- Wiley
- Published
- 2013-06-24
- Volume
- 119
- Issue
- 18
- Pages
- 3402-3410
- ISSN
- 0008-543X (ISSN-L)
- 1097-0142
- PMC
- PMC3775964
- OpenAlex
- W1602534286
- Cited by
- 91
- References
- 33
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 9 · 2022: 3 · 2021: 7 · 2020: 10 · 2019: 7 · 2018: 11 · 2017: 6 · 2016: 7 · 2015: 11 · 2014: 8 · 2013: 2
- FWCI
- 7.51
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Cancer (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000371)
- National Cancer Institute (CA 016672, P30CA016672)
- National Center for Research Resources (UL1RR024148)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Physical Sciences › Physics and Astronomy › Radiation › Advanced Radiotherapy Techniques
- Health Sciences › Medicine › Epidemiology › Multiple and Secondary Primary Cancers
- Keywords
- stereotactic body radiotherapy, multiple primary lung cancer, early-stage lung cancer, metachronous tumors, synchronous tumors, local control, overall survival, progression-free survival, radiation pneumonitis, curative treatment, second primary tumors
- MeSH terms
- Aged, Aged, 80 and over, Female, Humans, Lung Neoplasms, Male, Middle Aged, Neoplasms, Multiple Primary, Radiation Dosage, Retrospective Studies, Incidence, Survival Analysis, Radiosurgery, Treatment Outcome, Disease-Free Survival
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