Treatment and Prevention of Brain Metastases in Small Cell Lung Cancer

Abstract

Central nervous system (CNS) metastasis will develop in 50% of small cell lung cancer (SCLC) patients throughout disease course. Development of CNS metastasis poses a particular treatment dilemma due to the accompanied cognitive changes, poor permeability of the blood-brain barrier to systemic therapy and relatively advanced state of disease. Survival of patients with untreated SCLC brain metastases is generally < 3 months with whole brain radiotherapy used as first-line management in most SCLC patients. To prevent development of CNS metastasis prophylactic cranial irradiation (PCI) is recommended in limited stage disease, after response to chemotherapy and radiation, while PCI may be considered in extensive stage disease after favorable response to upfront treatment. Neurocognitive toxicity with whole brain radiotherapy and PCI is a concern and remains difficult to predict. The mechanism of toxicity is likely multifactorial, but a potential mechanism of injury to the hippocampus has led to hippocampal sparing radiation techniques. Treatment of established nonsmall cell lung cancer CNS metastases has increasingly focused on using stereotactic radiotherapy (SRS) and it is tempting to extrapolate these results to SCLC. In this review, we explore the evidence surrounding the prediction, prevention, detection, and treatment of CNS metastases in SCLC. We further review whether existing evidence supports extrapolating less toxic treatments to SCLC patients with CNS metastases and discuss trials that may shed more light on this question.

Safety and efficacy of anlotinib in combination with standard chemotherapy as first-line treatment for extensive-stage small cell lung cancer: A multi-center, prospective study (ACTION-2)

“…Our study highlights the clinical benefits of a combination regimen comprising anlotinib, and warrants further investigation of the same. About 30-50% of patients with ES-SCLC may experience brain metastasis, which has a significantly detrimental effect on their well-being [13]. The role of PCI in these patients post-treatment with platinum-etoposide remains controversial, with conflicting evidence available in the context of survival benefits, and the observation of debilitating side effects including cognitive disorders [14][15][16].…”

Real-world eligibility for platinum doublet plus immune checkpoint inhibitors in extensive-stage small-cell lung cancer

“…This results in uncertainty of the clinical benefit in these patients ( 11 ). Additionally, the inclusion of patients with brain metastases in ES SCLC trials is important given their high prevalence ( 20 ). CASPIAN allowed the enrollment of patients with brain metastases; however, it required patients to be either asymptomatic or treated off steroids and anticonvulsants ( 12 ).…”

Different clinical characteristics and survival between surgically resected pure and combined small cell lung cancer

“…[ 19 ] Although the reason for this had not yet been reported, from our study it could be clearly seen that adjuvant chemotherapy is an independent risk factor for SCLC patients, the majority of them being administered an SCLC regimen such as EP/EC (etoposide plus platinum), IP/IC (irinotecan plus platinum), etc. [ 24 , 25 ] SCLC and large cell neuroendocrine carcinoma are both neuroendocrine cancers, which may result in C‐SCLC/LCNEC patients responding better to conventional postoperative chemotherapy regimens and possibly account for a superior survival rate in patients than C‐SCLC/non‐LCNECs.…”