Ablative Radiation Therapy for Oligometastatic EGFR-Mutated Non-small Cell Lung Cancer: Who, Why, When, and How?

Abstract

Randomized trials1Vitzhum LK Pollom EL Diverging roads in the management of metastatic EGFR mutated non small cell lung cancer: Ablate all, none, or some?.Intl J Radiat Oncol Bio Phys. 2023; 116: 479-480Google Scholar have demonstrated improvements in progression-free survival and overall survival (OS) with consolidation stereotactic body radiation therapy after response to first-line systemic therapy for patients with oligometastatic non-small cell lung cancer (NSCLC).2Gomez DR Tang C Zhang J et al.Local consolidative therapy vs. maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer: Long-term results of a multi-institutional, phase II, randomized study.J Clin Oncol. 2019; 37: 1558-1565Crossref PubMed Scopus (645) Google Scholar Although patients with epidermal growth factor receptor (EGFR)–mutated NSCLC represented only a small portion of patients in the initial trials, there is strong rationale for ablating foci of tyrosine kinase inhibitor (TKI) resistance in this population. The recent phase 3 SINDAS trial, randomizing EGFR-positive patients to first-generation TKI ± upfront moderate-dose SBRT to all sites (≤5), demonstrated improved OS with upfront SBRT.3Wang XS, Bai YF, Verma V, et al. Randomized trial of first-line tyrosine kinase inhibitor with or without radiotherapy for synchronous oligometastatic EGFR-mutated NSCLC [e-pub ahead of print]. J Natl Cancer Inst. doi:10.1093/jnci/djac015, accessed February 23, 2023.Google Scholar Conversely, the recently completed NORTHSTAR trial (NCT03410043) randomized patients to osimertinib ± consolidative local therapy after 6 to 12 weeks of TKI. Similar to many oligometastatic trials, our practice has favored a consolidative approach with upfront TKI followed by SBRT to residual targetable disease, typically delivered around 2 to 6 months after TKI initiation. However, as supported by SINDAS, upfront SBRT is also evidence based.3Wang XS, Bai YF, Verma V, et al. Randomized trial of first-line tyrosine kinase inhibitor with or without radiotherapy for synchronous oligometastatic EGFR-mutated NSCLC [e-pub ahead of print]. J Natl Cancer Inst. doi:10.1093/jnci/djac015, accessed February 23, 2023.Google Scholar For the painful acetabular lesion, upfront SBRT is appropriate, but if symptoms improve rapidly on osimertinib, radiation could also be deferred to consolidation. For small asymptomatic brain metastases, our practice has generally been to initiate osimertinib and close surveillance with magnetic resonance imaging. However, data are limited regarding optimal timing and integration of SRS (eg, upfront, at progression, or as consolidation) with central nervous system–active TKIs and studies are ongoing (NCT03497767). Our definition of oligometastases in both the de novo and induced-oligometastatic setting generally follows the common trial definitions of up to 3 to 5 lesions. Lastly, we favor ablative-intent treatment while respecting organs at risk with dose-fractionation schedules (or their biological equivalents) in the range of 40 to 50 Gy in 5 fractions for the lung and 30 to 40 Gy in 5 fractions for the acetabulum.