Real-world insights into moderately hypofractionated thoracic radiotherapy in elderly and multimorbid patients with stage II/III NSCLC: a retrospective study

Authors

  • Helene Kravutske Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
  • Sina Mansoorian Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
  • Lukas Käsmann Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany; German Cancer Consortium (DKTK), partner site Munich; and German Cancer Research Center (DKFZ), Heidelberg, Germany; Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany
  • Janina Lehmann Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
  • Cedric Richlitzki Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
  • Diego Kauffmann-Guerrero Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany; Department of Medicine V, University Hospital, LMU Munich, Munich, Germany
  • Nina-Sophie Schmidt-Hegemann Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
  • Niels Reinmuth Department of Oncology, Asklepios Lung Clinic Munich-Gauting, Gauting, Germany
  • Amanda Tufman Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany; Department of Medicine V, University Hospital, LMU Munich, Munich, Germany
  • Julien Dinkel Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany; Department of Radiology, University Hospital, LMU Munich, Munich, Germany; Department of Radiology, Asklepios Lung Clinic Munich-Gauting, Gauting, Germany
  • Richard Gaus Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany; TUM School of Computation, Information and Technology, Munich, Germany
  • Farkhad Manapov Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
  • Claus Belka Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany; German Cancer Consortium (DKTK), partner site Munich; and German Cancer Research Center (DKFZ), Heidelberg, Germany; Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany; Bavarian Cancer Research Center (BZKF), Munich, Germany
  • Chukwuka Eze Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany; Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany

DOI:

https://doi.org/10.2340/1651-226X.2025.43496

Keywords:

hypofractionated radiotherapy, Non-small cell lung cancer, stage II/III, inoperable, frailty

Abstract

Purpose: Investigating real-world outcomes of moderately hypofractionated radiotherapy (hypoRT) in elderly and multimorbid stage IIB–IIIC non-small-cell lung cancer (NSCLC) patients ineligible for concurrent chemoradiation.

Methods: We retrospectively analysed 70 patients with primary or recurrent stage IIB–IIIC NSCLC (TNM, 8th edition). HypoRT was administered to a total dose of 38–56 Gy in 10–17 fractions (2.5–3.8 Gy/fraction). Patterns of recurrence, survival outcome, and toxicity were assessed.

Results: Seventy patients, with a median age of 76.4 years (range: 51.6–88.2 years), who received hypoRT between August 2015 and September 2022, were reviewed. At baseline, the median Charlson Comorbidity Index (CCI) with oncological diagnosis was 8 (range: 3–13). With a median follow-up post-radiotherapy of 63.9 months (95% Confidence Interval [CI]: 34.8–93.1 months), median progression-free survival (PFS) was 7.6 months (95% CI 6.0–11.0 months), and the median overall survival (OS) was 20.7 months (95% CI 16.7–30.7 months). Competing risk analysis revealed 12-month cumulative incidences of locoregional and distant failure in 41% (95% CI 30–53%) and 14% (95% CI 6–23%) of patients, respectively. Following disease progression, 45 patients received subsequent therapy: 25 underwent additional radiotherapy, 22 received systemic treatment (including immunotherapy), and 19 were referred for best supportive care. Treatment was well tolerated; only 3 patients (4%) developed grade 3 pneumonitis. No adverse events of grade > 3 were reported.

Interpretation: Moderately hypoRT is a safe, feasible, and effective treatment option for elderly and multimorbid patients with stage IIB–IIIC NSCLC, offering encouraging survival outcomes and low toxicity rates. Future prospective studies are needed to validate these findings and optimise treatment strategies for this high-risk population.

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References

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.

https://doi.org/10.3322/caac.21660 DOI: https://doi.org/10.3322/caac.21660

Ishida K, Hirose T, Yokouchi J, Oki Y, Kusumoto S, Sugiyama T, et al. Phase II study of concurrent chemoradiotherapy with carboplatin and vinorelbine for locally advanced non-small-cell lung cancer. Mol Clin Oncol. 2014;2(3):405–10.

https://doi.org/10.3892/mco.2014.252 DOI: https://doi.org/10.3892/mco.2014.252

Bonanno L, Attili I, Pavan A, Sepulcri M, Pasello G, Rea F, et al. Treatment strategies for locally advanced non-small cell lung cancer in elderly patients: translating scientific evidence into clinical practice. Crit Rev Oncol Hematol. 2021;163:103378.

https://doi.org/10.1016/j.critrevonc.2021.103378 DOI: https://doi.org/10.1016/j.critrevonc.2021.103378

Postmus PE, Kerr KM, Oudkerk M, Senan S, Waller DA, Vansteenkiste J, et al. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(suppl. 4):iv1–iv21.

https://doi.org/10.1093/annonc/mdx222 DOI: https://doi.org/10.1093/annonc/mdx222

Gray JE, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Three-year overall survival with durvalumab after chemoradiotherapy in stage III NSCLC-update from PACIFIC. J Thorac Oncol. 2020;15(2):288–93.

https://doi.org/10.1016/j.jtho.2019.10.002 DOI: https://doi.org/10.1016/j.jtho.2019.10.002

Yusuf D, Walton RN, Hurry M, Farrer C, Bebb DG, Cheung WY. Population-based treatment patterns and outcomes for stage III non-small cell lung cancer patients: a real-world evidence study. Am J Clin Oncol. 2020;43(9):615–20.

https://doi.org/10.1097/COC.0000000000000716 DOI: https://doi.org/10.1097/COC.0000000000000716

Brown S, Banfill K, Aznar MC, Whitehurst P, Faivre Finn C. The evolving role of radiotherapy in non-small cell lung cancer. Br J Radiol. 2019;92(1104):20190524.

https://doi.org/10.1259/bjr.20190524 DOI: https://doi.org/10.1259/bjr.20190524

Shrimali RK, Chakraborty S, Prasath S, Arun B, Chatterjee S. Impact of modern radiotherapy techniques on survival outcomes for unselect-ed patients with large volume non-small cell lung cancer. Br J Radiol. 2019;92(1095):20180928.

https://doi.org/10.1259/bjr.20180928 DOI: https://doi.org/10.1259/bjr.20180928

Gridelli C, Langer C, Maione P, Rossi A, Schild SE. Lung cancer in the elderly. J Clin Oncol. 2007;25(14):1898–907.

https://doi.org/10.1200/JCO.2006.10.3085 DOI: https://doi.org/10.1200/JCO.2006.10.3085

Nguyen LN, Komaki R, Allen P, Schea RA, Milas L. Effectiveness of accelerated radiotherapy for patients with inoperable non-small cell lung cancer (NSCLC) and borderline prognostic factors without distant metastasis: a retrospective review. Int J Radiat Oncol Biol Phys. 1999;44(5):1053–6.

https://doi.org/10.1016/S0360-3016(99)00130-3 DOI: https://doi.org/10.1016/S0360-3016(99)00130-3

Zhu ZF, Fan M, Wu KL, Zhao KL, Yang HJ, Chen GY, et al. A phase II trial of accelerated hypofractionated three-dimensional conformal radiation therapy in locally advanced non-small cell lung cancer. Radiother Oncol. 2011;98(3):304–8.

https://doi.org/10.1016/j.radonc.2011.01.022 DOI: https://doi.org/10.1016/j.radonc.2011.01.022

Parisi E, Genestreti G, Sarnelli A, Ghigi G, Arpa D, Burgio MA, et al. Accelerated hypofractionated radiotherapy plus chemotherapy for inoperable locally advanced non-small-cell lung cancer: final results of a prospective phase-II trial with a long-term follow-up. Radiat Oncol. 2019;14(1):112.

https://doi.org/10.1186/s13014-019-1317-x DOI: https://doi.org/10.1186/s13014-019-1317-x

Cannon DM, Mehta MP, Adkison JB, Khuntia D, Traynor AM, Tome WA, et al. Dose-limiting toxicity after hypofractionated dose-

escalated radiotherapy in non-small-cell lung cancer. J Clin Oncol. 2013;31(34):4343–8.

https://doi.org/10.1200/JCO.2013.51.5353 DOI: https://doi.org/10.1200/JCO.2013.51.5353

Valeriani M, Marinelli L, Nicosia L, Reverberi C, De Sanctis V, Mollo D, et al. Locally advanced inoperable primary or recurrent non-small cell lung cancer treated with 4-week hypofractionated radiation therapy (3 Gy/fraction). Radiol Med. 2019;124(12):1324–32.

https://doi.org/10.1007/s11547-019-01064-2 DOI: https://doi.org/10.1007/s11547-019-01064-2

Pollom EL, Qian Y, Durkee BY, von Eyben R, Maxim PG, Shultz DB, et al. Hypofractionated intensity-modulated radiotherapy for patients with non-small-cell lung cancer. Clin Lung Cancer. 2016;17(6):588–94.

https://doi.org/10.1016/j.cllc.2016.05.024 DOI: https://doi.org/10.1016/j.cllc.2016.05.024

Amini A, Lin SH, Wei C, Allen P, Cox JD, Komaki R. Accelerated hypofractionated radiation therapy compared to conventionally fractionated radiation therapy for the treatment of inoperable non-small cell lung cancer. Radiat Oncol. 2012;7:33.

https://doi.org/10.1186/1748-717X-7-33 DOI: https://doi.org/10.1186/1748-717X-7-33

Iyengar P, Zhang-Velten E, Court L, Westover K, Yan Y, Lin MH, et al. Accelerated hypofractionated image-guided vs conventional radio-therapy for patients with stage II/III non-small cell lung cancer and poor performance status: a randomized clinical trial. JAMA On-col. 2021;7(10):1497–505.

https://doi.org/10.1001/jamaoncol.2021.3186 DOI: https://doi.org/10.1001/jamaoncol.2021.3186

Eze C, Guggenberger JE, Schmidt-Hegemann NS, Kenndoff S, Taugner J, Käsmann L, et al. Pooled analysis on image-guided moderately hypofractionated thoracic irradiation in inoperable node-positive/recurrent patients with non-small cell lung cancer with poor prog-nostic factors and severely limited pulmonary function and reserve. Cancer. 2022;128(12):2358–66.

https://doi.org/10.1002/cncr.34201 DOI: https://doi.org/10.1002/cncr.34201

Eze C, Lombardo E, Nierer L, Xiong Y, Niyazi M, Belka C, et al. MR-guided radiotherapy in node-positive non-small cell lung cancer and severely limited pulmonary reserve: a report proposing a new clinical pathway for the management of high-risk patients. Radiat Oncol. 2022;17(1):43.

https://doi.org/10.1186/s13014-022-02011-8 DOI: https://doi.org/10.1186/s13014-022-02011-8

Eze C, Taugner J, Schmidt-Hegemann NS, Käsmann L, Guggenberger JE, Roengvoraphoj O, et al. Feasibility of hypofractionated radiothera-py in inoperable node-positive NSCLC patients with poor prognostic factors and limited pulmonary reserve: a prospective observa-tional study. Acta Oncol. 2021;60(8):1074–8.

https://doi.org/10.1080/0284186X.2021.1941244 DOI: https://doi.org/10.1080/0284186X.2021.1941244

Machtay M, Paulus R, Moughan J, Komaki R, Bradley JE, Choy H, et al. Defining local-regional control and its importance in locally ad-vanced non-small cell lung carcinoma. J Thorac Oncol. 2012;7(4):716–22.

https://doi.org/10.1097/JTO.0b013e3182429682 DOI: https://doi.org/10.1097/JTO.0b013e3182429682

Hansen O, Schytte T, Nielsen M, Brink C. Age dependent prognosis in concurrent chemo-radiation of locally advanced NSCLC. Acta Oncol. 2015;54(3):333–9.

https://doi.org/10.3109/0284186X.2014.958529 DOI: https://doi.org/10.3109/0284186X.2014.958529

Atagi S, Kawahara M, Yokoyama A, Okamoto H, Yamamoto N, Ohe Y, et al. Thoracic radiotherapy with or without daily low-dose car-boplatin in elderly patients with non-small-cell lung cancer: a randomised, controlled, phase 3 trial by the Japan Clinical Oncology Group (JCOG0301). Lancet Oncol. 2012;13(7):671–8.

https://doi.org/10.1016/S1470-2045(12)70139-0 DOI: https://doi.org/10.1016/S1470-2045(12)70139-0

Hofstetter K, Taugner J, Kasmann L, Mansoorian S, Florsch B, Eze C, et al. First-site-metastasis pattern in patients with inoperable stage III NSCLC treated with concurrent chemoradiotherapy with or without immune check-point inhibition: a retrospective analysis. Strah-lenther Onkol. 2024;200(7):614–23.

https://doi.org/10.1007/s00066-023-02175-6 DOI: https://doi.org/10.1007/s00066-023-02175-6

El-Marouk K, Käsmann L. [Longterm outcome of definitive radiotherapy using IMRT vs. 3D-CRT in locally advanced, inoperable non-small cell lung cancer (NSCLC)]. Strahlenther Onkol. 2025;201(2):198–200.

https://doi.org/10.1007/s00066-024-02327-2 DOI: https://doi.org/10.1007/s00066-024-02327-2

Feng A, Shao Y, Wang H, Chen H, Gu H, Duan Y, et al. A novel lung-avoidance planning strategy based on 4DCT ventilation imaging and CT density characteristics for stage III non-small-cell lung cancer patients. Strahlenther Onkol. 2021;197(12):1084–92.

https://doi.org/10.1007/s00066-021-01821-1 DOI: https://doi.org/10.1007/s00066-021-01821-1

Unterrainer M, Taugner J, Käsmann L, Tufman A, Reinmuth N, Li M, et al. Differential role of residual metabolic tumor volume in inopera-ble stage III NSCLC after chemoradiotherapy ± immune checkpoint inhibition. Eur J Nucl Med Mol Imaging. 2022;49(4):1407–16.

https://doi.org/10.1007/s00259-021-05584-w DOI: https://doi.org/10.1007/s00259-021-05584-w

Driessen EJM, Schulkes KJG, Dingemans AC, van Loon JGM, Hamaker ME, Aarts MJ, et al. Patterns of treatment and survival among older patients with stage III non-small cell lung cancer. Lung Cancer. 2018;116:55–61.

https://doi.org/10.1016/j.lungcan.2017.12.013 DOI: https://doi.org/10.1016/j.lungcan.2017.12.013

Driessen EJ, Bootsma GP, Hendriks LE, van den Berkmortel FW, Bogaarts BA, van Loon JG, et al. Stage III non-small cell lung cancer in the elderly: patient characteristics predictive for tolerance and survival of chemoradiation in daily clinical practice. Radiother Oncol. 2016;121(1):26–31.

https://doi.org/10.1016/j.radonc.2016.07.025 DOI: https://doi.org/10.1016/j.radonc.2016.07.025

Cacicedo J, Casquero F, Navarro A, Martinez-Indart L, Del Hoyo O,

Frías A, et al. Prospective multicentre analysis of the therapeutic approach and prognostic factors determining overall survival in elderly patients with non-small-cell lung carcinoma treated with curative intent. BJR Open. 2022;4(1):20210058.

https://doi.org/10.1259/bjro.20210058 DOI: https://doi.org/10.1259/bjro.20210058

Filippi AR, Campelo MRG, Paoli JB, Kowalski D, Bennati C, Borghetti P, et al. 66MO Durvalumab after radiotherapy (RT) in patients (pts) with unresectable stage III NSCLC ineligible for chemotherapy (CT): final analysis of the phase II DUART study. Immuno-Oncol Tech-nol. 2024;24:100809.

https://doi.org/10.1016/j.iotech.2024.100809 DOI: https://doi.org/10.1016/j.iotech.2024.100809

Yamada T, Goto Y, Tanaka H, Kimura H, Minato K, Gyotoku H, et al. A phase 2 trial of durvalumab treatment following radiation mono-therapy in patients with non-small cell lung cancer ineligible for stage III chemoradiotherapy: the SPIRAL-RT study. Eur J Cancer. 2023;195:113373.

https://doi.org/10.1016/j.ejca.2023.113373 DOI: https://doi.org/10.1016/j.ejca.2023.113373

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2025-07-25

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Kravutske, H., Mansoorian, S., Käsmann, L., Lehmann, J., Richlitzki, C., Kauffmann-Guerrero, D., … Eze, C. (2025). Real-world insights into moderately hypofractionated thoracic radiotherapy in elderly and multimorbid patients with stage II/III NSCLC: a retrospective study. Acta Oncologica, 64, 957–965. https://doi.org/10.2340/1651-226X.2025.43496

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Vol. 64 (2025): Acta Oncologica

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Copyright (c) 2025 Helene Kravutske, Sina Mansoorian, Lukas Käsmann, Janina Lehmann, Cedric Richlitzki, Diego Kauffmann-Guerrero, Nina-Sophie Schmidt-Hegemann, Niels Reinmuth, Amanda Tufman, Julien Dinkel, Richard Gaus, Farkhad Manapov, Claus Belka, Chukwuka Eze

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