Management of Leptomeningeal Metastases in Non-oncogene Addicted Non-small Cell Lung Cancer

Abstract

Brain metastases in non-small cell lung cancer (NSCLC) patients are more often detected due to imaging modalities improvements but also emerge because of improved treatments of the primary tumor which lead to a longer survival. In this context, development of leptomeningeal metastases (LM) is a devastating complication and its prognosis remains poor despite advances in systemic and local approaches. Histology characterization of NSCLC and molecular expression influence LM management. For those with “oncogene addiction,” new generation epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) were developed to strongly penetrate the blood-brain barrier (BBB) with the aim to prevent central nervous system cancer dissemination, eventually impacting on LM appearance and its subsequent management. Systemic chemotherapy, often combined with intrathecal chemotherapy (when possible), was one of common indications for lung cancer patients affected by LM, without driver mutations and a good performance status but currently, with the advent of innovative systemic approaches treatment solutions in this subgroup of patients are rapidly evolving. Whole brain radiation therapy (WBRT) is the conventional treatment for patients with brain metastases. Furthermore, modern radiation techniques, as stereotactic radiotherapy (SRT), improve outcomes in those cases with a limited number of lesions. However, LM represent a minority of CNS metastases and few literature data are available to drive the radiotherapy approach. Considering all relevant progress made in this setting, after a literature review, the aim of this paper is to discuss about recent developments and therapeutic options in LM management of non-oncogene addicted NSCLC.

Outcome of Patients with Non–Small Cell Lung Cancer and Brain Metastases Treated with Checkpoint Inhibitors

“…Patients with leptomeningeal metastases (LMs) were excluded, as the prognosis of patients with LMs is usually poorer than that of patients with BMs. 29 These patients will be reported separately.…”

Brain metastases, patterns of intracranial progression, and the clinical value of upfront cranial radiotherapy in patients with metastatic non-small cell lung cancer treated with PD-1/PD-L1 inhibitors

“…All included patients had histologically confirmed NSCLC and complete follow-up data. Patients with leptomeningeal metastases were excluded due to their extremely poor prognosis (11). Electronic patient records were reviewed, and the relevant demographic and clinical information was extracted, including sex, age at anti-PD-1/PD-L1 therapy, line of PD-(L)1 inhibitor treatment, smoking history, tumor histology, PD-L1 expression status, Eastern Cooperative Oncology Group performance status (ECOG PS), number of organs harboring metastases, presence or absence of BMs, number of BMs, diameter of the largest BM, clinical presentation (symptomatic vs. asymptomatic), treatment regimen (monotherapy or combined with chemotherapy), and prior RT for BMs.…”

Two Cases of Cranial Nerve Metastasis Treated with Radiotherapy and Chemotherapy in Patients with Lung Adenocarcinoma

“…Lung cancer is the most common cause of cancer-related deaths worldwide [ 1 ]. The incidence of central nervous system metastasis is known to be high among patients with lung cancer [ 2 ]. In fact, the frequency of brain metastasis and carcinomatous meningitis during an entire clinical course of non-small cell lung cancer (NSCLC) is reported to be about 40% and 5%, respectively [ 2 ].…”

“…The incidence of central nervous system metastasis is known to be high among patients with lung cancer [ 2 ]. In fact, the frequency of brain metastasis and carcinomatous meningitis during an entire clinical course of non-small cell lung cancer (NSCLC) is reported to be about 40% and 5%, respectively [ 2 ]. In contrast, cranial nerve metastasis is extremely rare, and its frequency among lung cancer patients has not been reported.…”