Thoracic irradiation as consolidation therapy in patients with extensive-stage small cell lung cancer

Abstract

Purpose of reviewSmall cell lung cancer (SCLC) is marked by an exceptionally high proliferative rate and poor prognosis. Given its high propensity to metastasize, nearly two-thirds of SCLC patients are diagnosed with extensive-stage (ES) disease when surgery is not a treatment option anymore. Over several decades, only minimal changes have been made in the therapeutic armamentarium of ES-SCLC. Recently, however, several new therapeutic avenues were defined, thus renewing the hope for patients with this recalcitrant cancer. Here, we present an overview of the most current therapeutic advances in ES-SCLC focusing in particular on consolidative thoracic radiation therapy (cTRT) and chemo-immunotherapy.Recent findingsThe incorporation of immunotherapy in the standard-of-care of ES-SCLC patients and the resulting outcomes are both a remarkable hallmark of progress and a disappointment. Indeed, chemo-immunotherapy with or without cTRT and prophylactic cranial irradiation contributes to longer survival outcomes with minimal toxicity rates in well selected and properly monitored patients. Nevertheless, the gain in overall survival is still modest relative to that seen in many other solid tumors.SummaryDespite the encouraging results, further clinical trials are needed to determine the efficacy and safety of these therapeutic approaches, and moreover, to identify new predictive biomarkers of response.

Clinical insights into small cell lung cancer: Tumor heterogeneity, diagnosis, therapy, and future directions

“…In contrast to chemotherapy alone, administration of PD‐L1 inhibitors within the framework of chemoimmunotherapy is not terminated after four to six cycles, and maintenance immunotherapy is continued until progression 184 . This raises questions about the applicability of radiotherapy in this setting because the effects of both consolidative thoracic radiotherapy and PCI were primarily interpreted in chemotherapy‐treated patients after termination of systemic therapy 230 . Current practice guidelines support the idea that consolidative thoracic radiotherapy can be applied both before and during maintenance immunotherapy 184 .…”

“…Further data on the benefit of thoracic radiotherapy in the context of chemoimmunotherapy will be delivered by the RAPTOR/NRG LU007 trial (ClinicalTrials.gov identifier NCT04402788) 248 . To date, the benefit of PCI in patients with active tumor control achieved by immunotherapy maintenance is unclear 230 . For patients with limited stage disease, consolidative pembrolizumab had favorable tolerability and activity in a recent phase 1/2 trial 249 .…”

“…228,229 In addition to its use in limited stage SCLC, radiotherapy can also be administered as part of consolidation therapy for residual tumor eradication in extensive-stage disease (Figure 6). 230 It should be noted, however, that radiotherapy in this patient population primarily offers delayed survival benefits: a large, phase 3, randomized controlled trial demonstrated that thoracic radiotherapy after chemotherapy did not significantly improve the survival outcomes at 1 year in patients with extensive-stage disease. 231 However, in that study, the 2-year OS was significantly improved, and PFS was also significantly greater in the thoracic radiotherapy group.…”

Progress in radiotherapy for small‐cell lung cancer

“…94 In addition, patients with superior vena cava syndrome, central airway compression, or atelectasis may benefit from cTRT. 95…”

“…Furthermore, in accordance with contemporary ESMO clinical practice guidelines, cTRT should only be taken into account in ES‐SCLC patients with PS 0–1 and contraindication to immunotherapy, or patients with PS 2 and a positive response to chemotherapy 94 . In addition, patients with superior vena cava syndrome, central airway compression, or atelectasis may benefit from cTRT 95 …”