Radiotherapy for brain metastases from small-cell lung cancer in distinct clinical indications and scenarios

Abstract

Small-cell lung cancer (SCLC) is a rapidly progressing disease with a predilection for early metastasizing. The most common site of metastases is the brain; about 40-50% of patients develop brain metastases (BM) within 2 years from diagnosis (1). Radiotherapy plays a crucial role in the management of BM from SCLC. However, there are a number of distinct biological and clinical characteristics of SCLC that preclude the direct incorporation of the results of the studies on the treatment of BM from other solid tumors to the management of BM from SCLC. These are: the high aggressiveness of the disease with rapid micro-and macro-dissemination to the brain, the rare occurrence without the presence of extracranial disease, chemo-sensitivity that incites the use of systemic treatment, the use of prophylactic cranial irradiation (PCI) as a part of the standard strategy for patients without BM, and a dismal disease course. The historical treatment of BM from SCLC was whole-brain radiotherapy (WBRT) alone or combined with chemotherapy (CHT). The outcome of such strategies was poor; median overall survival (OS) after WBRT was 3.0-4.7 months in both prospective and retrospective studies (2-5). However, a temporal trend towards a slight survival improvement in SCLC exists (6) and is also seen for patients with BM in recently published

Distribution characteristics and prognosis of tumor-infiltrating lymphocytes in the brain metastases of small cell lung cancer: a retrospective cohort study

“…The blockade of PD-1/PD-L1 pathway through anti-PD-1 or anti-PD-L1 monoclonal antibodies restore anti-tumoral immune response. The administration of anti-PD-L1 antibodies combined with platinum-based chemo has become standard first-line treatment for extensive stage SCLC ( 5 - 8 ). In fact, a meta-analysis showed an OS benefit for patients treated with ICI + chemo vs. chemo alone, but patients with brain metastases were few and no definitive conclusions may be drawn ( 9 ).…”

Primary systemic therapy for patients with brain metastases from lung cancer ineligible for targeted agents

“…In this context, the progress made for NSCLC was more remarkable than for SCLC, the predominant type of cancer in our study. In SCLC, PCI has been shown to improve survival (Kepka et al 2021 ). One might argue that the common setting of four cycles of chemotherapy followed by planned WBRT in many SCLC patients in our study resembles the PCI concept.…”

“…For example, the simultaneous presence of widespread extracranial disease, an actionable mutation and limited, asymptomatic brain disease may prompt the multidisciplinary tumor board (MDT) to recommend this strategy. Despite a long-standing, historical interest in primary cytotoxic chemotherapy for selected patients with SCLC and NSCLC with brain metastases (Minotti et al 1998 ; Bernardo et al 2002 ; Chen et al 2008 ; Lee et al 2008 ), early administration of radiotherapy was common (Nieder et al 2019a , b ; Kepka et al 2021 ; Du et al 2021 ). Under special circumstances, surgical resection of a single brain metastasis may be a viable option (Fuchs et al 2021 ).…”

Canadian Consensus Recommendations on the Management of Extensive-Stage Small-Cell Lung Cancer

“…About 50% of patients with SCLC develop brain metastases [111][112][113][114] and pose treatment dilemmas due to cognitive changes, diminished blood-brain barrier permeability to systemic therapy, and relatively advanced disease state. Radiotherapy plays a major role in the treatment of brain metastases in patients with SCLC [115].…”