BACKGROUND: Stereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable early-stage non-small cell lung cancer (ES-NSCLC), but which patients benefit from stereotactic radiotherapy is unclear. The aim of this study was to analyze prognostic factors for early mortality. METHODS: From August 2010 to 2022, 617 patients with medically inoperable, peripheral or central ES-NSCLC were treated with SABR at our institution. We retrospectively evaluated the data from 172 consecutive patients treated from 2018 to 2020 to analyze the prognostic factors associated with overall survival (OS). The biological effective dose was > 100 Gy10 in all patients, and 60 Gy was applied in 3-5 fractions for a gross tumor volume (GTV) + 3 mm margin when the tumor diameter was < 1 cm; 30-33 Gy was delivered in one fraction. Real-time tumor tracking or an internal target volume approach was applied in 96% and 4% of cases, respectively. In uni- and multivariate analysis, a Cox model was used for the following variables: ventilation parameter FEV1, histology, age, T stage, central vs. peripheral site, gender, pretreatment PET, biologically effective dose (BED), and age-adjusted Charlson comorbidity index (AACCI). RESULTS: The median OS was 35.3 months. In univariate analysis, no correlation was found between OS and ventilation parameters, histology, PET, or centrality. Tumor diameter, biological effective dose, gender, and AACCI met the criteria for inclusion in the multivariate analysis. The multivariate model showed that males (HR 1.51, 95% CI 1.01-2.28; p = 0.05) and AACCI > 5 (HR 1.56, 95% CI 1.06-2.31; p = 0.026) were significant negative prognostic factors of OS. However, the analysis of OS showed that the significant effect of AACCI > 5 was achieved only after 3 years (3-year OS 37% vs. 56%, p = 0.021), whereas the OS in one year was similar (1-year OS 83% vs. 86%, p = 0.58). CONCLUSION: SABR of ES-NSCLC with precise image guidance is feasible for all medically inoperable patients with reasonable performance status. Early deaths were rare in our real-life cohort, and OS is clearly higher than would have been expected after best supportive care.

Department of Biomedical Technology Faculty of Biomedical Engineering Czech Technical University Prague Kladno Czech Republic

Department of Oncology University Hospital Olomouc Olomouc Czech Republic

Dept of Oncology University Hospital Ostrava 17 listopadu 1790 708 52 Ostrava Czech Republic

Faculty of Medicine and Dentistry Palacky University Olomouc Olomouc Czech Republic

Faculty of Medicine University of Ostrava Ostrava Czech Republic

Zobrazit více v PubMed

Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. Ca Cancer J Clin. 2021;71(1):7–33. doi: 10.3322/caac.21654. PubMed DOI

Zheng X, Schipper M, Kidwell K, Lin J, Reddy R, Ren Y, Kong FMS. Survival outcome after stereotactic body radiation therapy and surgery for stage I non-small cell lung cancer: a meta-analysis. Int J Radiation Oncology* Biology* Phys. 2014;90(3):603–11. doi: 10.1016/j.ijrobp.2014.05.055. PubMed DOI

Brooks ED, Sun B, Zhao L, Komaki R, Liao Z, Jeter M, Chang JY. Stereotactic ablative radiation therapy is highly safe and effective for elderly patients with early-stage non-small cell lung cancer. Int J Radiation Oncology* Biology* Phys. 2017;98(4):900–7. doi: 10.1016/j.ijrobp.2016.12.022. PubMed DOI PMC

Lee P, Loo Jr BW, Biswas T, Ding GX, Naqa E, Jackson IM, Li A. Local control after stereotactic body radiation therapy for stage I non-small cell lung cancer. Int J Radiation Oncology* Biology* Phys. 2021;110(1):160–71. doi: 10.1016/j.ijrobp.2019.03.045. PubMed DOI PMC

Li M, Yang X, Chen Y, Yang X, Dai X, Sun F, Wang Q. (2017). Stereotactic body radiotherapy or stereotactic ablative radiotherapy versus surgery for patients with T1-3N0M0 non-small cell lung cancer: a systematic review and meta-analysis. OncoTargets Therapy, 2885–92. PubMed PMC

Guckenberger M, Andratschke N, Dieckmann K, Hoogeman MS, Hoyer M, Hurkmans C, Verellen D. ESTRO ACROP consensus guideline on implementation and practice of stereotactic body radiotherapy for peripherally located early stage non-small cell lung cancer. Radiother Oncol. 2017;124(1):11–7. doi: 10.1016/j.radonc.2017.05.012. PubMed DOI

Wao H, Mhaskar R, Kumar A, Miladinovic B, Djulbegovic B. Survival of patients with non-small cell lung cancer without treatment: a systematic review and meta-analysis. Syst Reviews. 2013;2:1–11. doi: 10.1186/2046-4053-2-10. PubMed DOI PMC

Guckenberger M. Stereotaktische Strahlentherapie Bei Lungenkrebs Im Stadium I–gibt es eine Evidenz? Zentralblatt für Chirurgie-Zeitschrift für Allgemeine Viszeral- Thorax-und Gefäßchirurgie. 2017;142(S 01):S17–25. doi: 10.1055/s-0043-117177. PubMed DOI

Schonewolf CA, Heskel M, Doucette A, Singhal S, Frick MA, Xanthopoulos EP, Simone II. Five-year long-term outcomes of stereotactic body radiation therapy for operable versus medically inoperable stage i non–small-cell lung cancer: analysis by operability, fractionation regimen, tumor size, and tumor location. Clin Lung Cancer. 2019;20(1):e63–71. doi: 10.1016/j.cllc.2018.09.004. PubMed DOI

Kopek N, Paludan M, Petersen J, Hansen AT, Grau C, Høyer M. Co-morbidity index predicts for mortality after stereotactic body radiotherapy for medically inoperable early-stage non-small cell lung cancer. Radiother Oncol. 2009;93(3):402–7. doi: 10.1016/j.radonc.2009.06.002. PubMed DOI

Yang CC, Fong Y, Lin LC, Que J, Ting WC, Chang CL, Huang CI. The age-adjusted Charlson comorbidity index is a better predictor of survival in operated lung cancer patients than the Charlson and Elixhauser comorbidity indices. Eur J Cardiothorac Surg. 2018;53(1):235–40. doi: 10.1093/ejcts/ezx215. PubMed DOI

Baker S, Sharma A, Peric R, Heemsbergen WD, Nuyttens JJ. Prediction of early mortality following stereotactic body radiotherapy for peripheral early-stage lung cancer. Acta Oncol. 2019;58(2):237–42. doi: 10.1080/0284186X.2018.1532602. PubMed DOI

Taylor JM, Song A, David AR, Chen VE, Lu B, Werner-Wasik M. (2020). Impact of Sarcopenia on survival in patients with early-stage lung cancer treated with stereotactic body radiation therapy. Cureus, 12(9). PubMed PMC

Criner GJ, Agusti A, Borghaei H, Friedberg J, Martinez FJ, Miyamoto C, Celli BR. Chronic obstructive pulmonary disease and lung cancer: a review for clinicians. Chronic Obstr Pulmonary Diseases: J COPD Foundation. 2022;9(3):454. PubMed PMC

Koshy M, Malik R, Spiotto M, Mahmood U, Weichselbaum R, Sher D. Disparities in treatment of patients with inoperable stage I non–small cell lung cancer: a population-based analysis. J Thorac Oncol. 2015;10(2):264–71. doi: 10.1097/JTO.0000000000000418. PubMed DOI PMC

Baker S, Bakunina K, Duijm M, Hoogeman MS, Cornelissen R, Antonisse I, Nuyttens JJ. Development and external validation of a nomogram to predict overall survival following stereotactic body radiotherapy for early-stage lung cancer. Radiat Oncol. 2020;15(1):1–11. doi: 10.1186/s13014-020-01537-z. PubMed DOI PMC

Abel S, Hasan S, White R, Schumacher L, Finley G, Colonias A, Wegner RE. Stereotactic ablative radiotherapy (SABR) in early stage non-small cell lung cancer: comparing survival outcomes in adenocarcinoma and squamous cell carcinoma. Lung Cancer. 2019;128:127–33. doi: 10.1016/j.lungcan.2018.12.022. PubMed DOI

Deshpande SR, Podder TK, Grubb W, Zhang Y, Zheng Y, Towe C, Biswas T. (2023). Pretreatment and posttreatment tumor metabolic activity assessed by FDG-PET/CT as predictors of Tumor recurrence and survival outcomes in early-stage Non-small Cell Lung Cancer treated with stereotactic body Radiation Therapy. Adv Radiation Oncol, 101313. PubMed PMC

Duijm M, Oomen-de Hoop E, van der Zyp NVV, van de Vaart P, Tekatli H, Hoogeman M, Nuyttens JJ. The development and external validation of an overall survival nomogram in medically inoperable centrally located early-stage non-small cell lung carcinoma. Radiother Oncol. 2021;156:223–30. doi: 10.1016/j.radonc.2020.12.038. PubMed DOI

Klement RJ, Belderbos J, Grills I, Werner-Wasik M, Hope A, Giuliani M, Guckenberger M. Prediction of early death in patients with early-stage NSCLC—can we select patients without a potential benefit of SBRT as a curative treatment approach? J Thorac Oncol. 2016;11(7):1132–9. doi: 10.1016/j.jtho.2016.03.016. PubMed DOI

Lin Y, Qureshi MM, Batra S, Truong MT, Mak KS. (2021). Consecutive Daily vs. Every other Day SBRT Scheduling for Stage I NSCLC. Int J Radiat Oncol Biol Phys, 111(3), e444.

Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47(11):1245–51. doi: 10.1016/0895-4356(94)90129-5. PubMed DOI

Pauwels RA, Buist AS, Calverley PM, Jenkins CR, Hurd SS. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) workshop summary. Am J Respir Crit Care Med. 2001;163(5):1256–76. doi: 10.1164/ajrccm.163.5.2101039. PubMed DOI

Knybel L, Cvek J, Molenda L, Stieberova N, Feltl D. Analysis of lung tumor motion in a large sample: patterns and factors influencing precise delineation of internal target volume. Int J Radiation Oncology* Biology* Phys. 2016;96(4):751–8. doi: 10.1016/j.ijrobp.2016.08.008. PubMed DOI

Common Toxicity Criteria for Adverse Events version 4.0. National Cancer Institute [online]. 2023 [cit. 2023-12-20]. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_50.

Timmerman RD, Hu C, Michalski J, Straube W, Galvin J, Johnstone D, Choy H. Long-term results of RTOG 0236: a phase II trial of stereotactic body radiation therapy (SBRT) in the treatment of patients with medically inoperable stage I non-small cell lung cancer. Int J Radiat Oncol Biol Phys. 2014;90(1):S30. doi: 10.1016/j.ijrobp.2014.05.135. DOI

Nyman J, Hallqvist A, Lund JÅ, Brustugun OT, Bergman B, Bergström P, Lax I. SPACE–a randomized study of SBRT vs conventional fractionated radiotherapy in medically inoperable stage I NSCLC. Radiother Oncol. 2016;121(1):1–8. doi: 10.1016/j.radonc.2016.08.015. PubMed DOI

Ball D, Mai GT, Vinod S, Babington S, Ruben J, Kron T, Le H. Stereotactic ablative radiotherapy versus standard radiotherapy in stage 1 non-small-cell lung cancer (TROG 09.02 CHISEL): a phase 3, open-label, randomised controlled trial. Lancet Oncol. 2019;20(4):494–503. doi: 10.1016/S1470-2045(18)30896-9. PubMed DOI

Jochems A, El-Naqa I, Kessler M, Mayo CS, Jolly S, Matuszak M, Lambin P. A prediction model for early death in non-small cell lung cancer patients following curative-intent chemoradiotherapy. Acta Oncol. 2018;57(2):226–30. doi: 10.1080/0284186X.2017.1385842. PubMed DOI PMC

Videtic GM, Paulus R, Singh AK, Chang JY, Parker W, Olivier KR, Bradley JD. Long-term follow-up on NRG Oncology RTOG 0915 (NCCTG N0927): a randomized phase 2 study comparing 2 stereotactic body radiation therapy schedules for medically inoperable patients with stage I peripheral non-small cell lung cancer. Int J Radiation Oncology* Biology* Phys. 2019;103(5):1077–84. doi: 10.1016/j.ijrobp.2018.11.051. PubMed DOI PMC

Onishi H, Araki T, Shirato H, Nagata Y, Hiraoka M, Gomi K, Yamada K. Stereotactic hypofractionated high-dose irradiation for stage I nonsmall cell lung carcinoma: clinical outcomes in 245 subjects in a Japanese multiinstitutional study. Cancer. 2004;101(7):1623–31. doi: 10.1002/cncr.20539. PubMed DOI

Koshy M, Malik R, Weichselbaum RR, Sher DJ. Increasing radiation therapy dose is associated with improved survival in patients undergoing stereotactic body radiation therapy for stage I non–small-cell lung cancer. Int J Radiation Oncology* Biology* Phys. 2015;91(2):344–50. doi: 10.1016/j.ijrobp.2014.10.002. PubMed DOI

Kestin L, Grills I, Guckenberger M, Belderbos J, Hope AJ, Werner-Wasik M, Elekta Lung Research Group Dose–response relationship with clinical outcome for lung stereotactic body radiotherapy (SBRT) delivered via online image guidance. Radiother Oncol. 2014;110(3):499–504. doi: 10.1016/j.radonc.2014.02.002. PubMed DOI

Inagaki T, Doi H, Ishida N, Ri A, Tatsuno S, Wada Y, Nishimura Y. Escalated maximum dose in the planning target volume improves local control in stereotactic body radiation therapy for T1-2 lung cancer. Cancers. 2022;14(4):933. doi: 10.3390/cancers14040933. PubMed DOI PMC

Bezjak A, Paulus R, Gaspar LE, Timmerman RD, Straube WL, Ryan WF, Choy H. Efficacy and toxicity analysis of NRG Oncology/RTOG 0813 trial of stereotactic body radiation therapy (SBRT) for centrally located non-small cell lung cancer (NSCLC) Int J Radiat Oncol Biol Phys. 2016;96(2):S8. doi: 10.1016/j.ijrobp.2016.06.035. DOI

Shu Z, Dong B, Shi L, Shen W, Hang Q, Wang J, Chen Y. Stereotactic body radiotherapy for elderly patients (≥ 75 years) with early-stage non-small cell lung cancer. J Cancer Res Clin Oncol. 2020;146:1263–71. doi: 10.1007/s00432-020-03154-5. PubMed DOI PMC

Watanabe K, Katsui K, Sugiyama S, Yoshio K, Kuroda M, Hiraki T, Kanazawa S. Lung stereotactic body radiation therapy for elderly patients aged ≥ 80 years with pathologically proven early-stage non-small cell lung cancer: a retrospective cohort study. Radiat Oncol. 2021;16(1):1–8. doi: 10.1186/s13014-021-01769-7. PubMed DOI PMC

Soler JJ, Martínez-García MÁ, Román P, Salcedo E, Navarro M, Ochando R. (2005). Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax. PubMed PMC

Baumann P, Nyman J, Hoyer M, Gagliardi G, Lax I, Wennberg B, Lewensohn R. Stereotactic body radiotherapy for medically inoperable patients with stage I non-small cell lung cancer–a first report of toxicity related to COPD/CVD in a non-randomized prospective phase II study. Radiother Oncol. 2008;88(3):359–67. doi: 10.1016/j.radonc.2008.07.019. PubMed DOI

Allibhai Z, Taremi M, Bezjak A, Brade A, Hope AJ, Sun A, Cho BJ. The impact of tumor size on outcomes after stereotactic body radiation therapy for medically inoperable early-stage non-small cell lung cancer. Int J Radiation Oncology* Biology* Phys. 2013;87(5):1064–70. doi: 10.1016/j.ijrobp.2013.08.020. PubMed DOI

Tateishi Y, Takeda A, Horita N, Tsurugai Y, Eriguchi T, Kibe Y, Kaneko T. Stereotactic body radiation therapy with a high maximum dose improves local control, cancer-specific death, and overall survival in peripheral early-stage non-small cell lung cancer. Int J Radiation Oncology* Biology* Phys. 2021;111(1):143–51. doi: 10.1016/j.ijrobp.2021.04.014. PubMed DOI