MS07.05 Stage I (Resectable) NSCLC: Radiation

Abstract

For patients with a peripheral stage I NSCLC, the non-surgical treatment of choice is stereotactic ablative radiotherapy (SABR). Patients who are fit to undergo surgery, but instead undergo SABR, have a 3-year overall survival ranging from 76-86% [Siva S, Oncologist 2016], which is superior overall survivals in medically unfit patients treated using SABR. In 2013, the ESMO Clinical Practice Guidelines recommeded that surgery ‘should be offered to patients with stage I or II NSCLC who are willing to accept procedure-related risks’ [Vansteenkiste J, Ann Oncol 2013]. In the absence of completed randomized clinical trials of surgery versus SABR, a number of recent propensity score matched analyses have been performed. A pooled meta-analysis of propensity score matched data showed no significant differences in cancer specific survival between the two local treatments [Chen H, IJROBP 2018]. Changes in the treatment patterns for patients with early-stage NSCLC have be reported in a number of countries, all showing an increase in the utilization of SABR in mainly elderly patients [Damhuis R, Ann Oncol 2019; Holmes JA, JNCI Ca Spectrum 2017]. These findings are in part due to the increase in the frail elderly presenting with lung cancer, and to the growing awareness of treatment-related mortality in this population. For example, data from the US National Cancer Database revealed that differences in 30- and 90-day post-treatment mortality between surgery and SABR increased as a function of age, with the largest differences in favor of SABR observed among patients older than 70 years [Stokes WA, JCO 2018[. Ongoing and future randomized studies comparing both modalities will also have to take account of the view of patient preferences. This is illustrated by recent randomized trial of surgery versus SABR (SABRTOOTH, ISRCTN13029788), in which 84 high-risk patients were approached by pulmonologists and oncology nurses for study participation, and 24 (29%) were randomized [Franks K, WCLC 2018]. The main reason for declining study participation was patient preference with 29% preferring surgery and 42% SABR. Overall 9 patients (38%) did not receive their randomized treatment. Of 7 patients who had been randomized to surgery but not undergoing surgery, 6 received SABR, 1 radical radiotherapy. Similarly, of 2 patients randomized to SABR, but who did not undergo SABR, 1 patient received radical radiotherapy, and another was lost to follow-up. Other research which may influence the ongoing debate are the effects of both local therapies on the immune system. The systemic inflammatory response induced after surgery can promote the emergence of tumors whose growth was otherwise restricted by a tumor-specific T cell response [Krall 2018]. SABR, on the other hand, is actively being investigated as an immunomodulator to enhance systemic anticancer effects [Marciscano AE, IJROBP 2019], with a randomized placebo-controlled trial of immune-checkpoint blockade underway in this population (NCT03833154). REFERENCES Siva S. Curing Operable Stage I Non-Small Cell Lung Cancer With Stereotactic Ablative Body Radiotherapy: The Force Awakens. The Oncologist 2016;21:393–398 Vansteenkiste J. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013 Oct;24 Suppl 6:vi89-98. Chen H. Stereotactic Ablative Radiation Therapy Versus Surgery in Early Lung Cancer: A Meta-analysis of Propensity Score Studies. Int J Radiat Oncol Biol Phys 101:186-194, 2018 Damhuis R. Annals of Oncology (2019) 30 (suppl_2): ii26-ii30. 10.1093/annonc/mdz064 Holmes JA, JNCI Cancer Spectrum, Volume 1, Issue 1, September 2017, https://doi.org/10.1093/jncics/pkx003 Stokes WA. Post-Treatment Mortality After Surgery and Stereotactic Body Radiotherapy for Early-Stage Non-Small-Cell Lung Cancer. J Clin Oncol2018 Mar 1;36(7):642-651. Franks K. SABRTOOTH: A Feasibility Study of SABR Versus Surgery in Patients with Peripheral Stage I NSCLC Considered to be at Higher Risk for Surgery. Proceedings of WCLC 2018 P2.16-16 Marciscano AE. Immunomodulatory Effects of Stereotactic Body Radiation Therapy: Preclinical Insights and Clinical Opportunities. In press Int J Radiat Oncol Biol Phys 2019 https://doi.org/10.1016/j.ijrobp.2019.02.046 Krall JA. The systemic response to surgery triggers the outgrowth of distant immune-controlled tumors in mouse models of dormancy. Sci. Transl. Med. 10, eaan3464 (2018) surgery, Early-stage lung cancer, stereotactic radiotherapy