A narrative review of evolving roles of radiotherapy in advanced non-small cell lung cancer: from palliative care to active player

Radiotherapy, along with other loco-regional interventions, is conventionally utilized as a palliative approach to alleviate symptoms and mitigate oncological emergencies in advanced non-small cell lung cancer (NSCLC). Thanks to the ongoing improvement of medical treatments in the last decade, such as targeted therapy and immunotherapy, the survival of patients with advanced NSCLC has been considerably prolonged, making it feasible and clinically beneficial for radiotherapy to play a more active role in highly selected subpopulations. In this review, we will focus on the evolving roles of radiotherapy in advanced NSCLC. First of all, among patients who are initially unable to tolerate aggressive treatment due to severe symptoms caused by metastases and/or tumor emergencies, timely radiotherapy could significantly improve their performance status (PS) and general condition, thus giving them a chance for intensive treatment and prolonged survival. The efficacy, potential candidates, and optimal dose-fractionation regimens of radiotherapy in this clinical scenario will be discussed. Additionally, radiotherapy can play a curative role as a concurrent therapy, consolidation therapy, and salvage therapy for patients with oligo-metastatic, oligo-residual, and oligo-progressive disease, respectively. Accumulating evidence from recent clinical trials, basic research, and translational investigations regarding the potentially curative roles of radiotherapy in NSCLC patients with oligo-metastatic disease will be summarized. Moreover, with the advent of various small molecular tyrosine kinase inhibitors (TKIs), the treatment efficacy and overall survival of oncogene-addicted NSCLC with brain metastases have been significantly improved, and the clinical value and optimal timing of cranial radiotherapy have become topics of much debate. Finally, synergistic antitumor interactions between radiotherapy and immunotherapy have been repeatedly demonstrated. Thus, the immune sensitizing role of radiotherapy in advanced NSCLC is also highlighted in this review.