Leptomeningeal metastasis from non-small cell lung cancer – a post-hoc analysis from four randomised clinical trials

Abstract

Background Leptomeningeal metastasis (LMM) from non-small cell lung cancer (NSCLC) is often an underdiagnosed entity, has a dismal prognosis and has very limited data from low- and middle-income countries. Methods A single-centre study, which included 1148 adult patients diagnosed as NSCLC, with Eastern Oncology Cooperative Group performance status 0–2, as identified from data of four prospective randomised controlled trials. Two trials included patients who had epidermal growth factor sensitive mutations (CTRI/2015/08/006113 and CTRI/2016/08/007149) and the other two included squamous cell carcinoma (CTRI/2013/02/003422) and adenocarcinoma patients (CTRI/2014/08/00484). The key objectives were to estimate the incidence, risk factors, time to development and outcomes for LMM. Results Out of 1148 patients, 36 patients (0.031%; 95%CI: 0.022–0.043) developed leptomeningeal metastasis. In these patients, median time to development of LM was 14.92 months (interquartile range: 7.7–21.84). Among the tested factors, the presence of brain metastasis was the only statistically significant risk factor associated with the development of LMM ( p -value = 0.035). The median overall survival (OS) after the development of LM was 61 days (95%CI: 38.95–83.05). The median OS in driver mutated patients was 66 days (95% CI: 14.74–117.26) versus 51 days (95% CI: 14.5–87.5) ( p -value = 0.201) in non-driver mutated patients. Only 6 (19.4%) out of 31 epidermal growth factor receptor-mutated patients received osimertinib. Patients treated with osimertinib had a median OS of 245 days (95% CI: 215.48–274.52) versus 52 days (95% CI: 22.62–81.38) for those without ( p -value = 0.327). Conclusion The incidence of LMM is low in the Indian population. In our study, there was no single factor which impacted survival in patients who developed LMM. This suggests that the overall prognosis is poor in patients with LMM where access to newer therapeutic modalities is limited.

Treatment pattern and outcomes of leptomeningeal carcinomatosis in India – a retrospective study

“…In that study there was trend towards improved outcomes in patients who were treated with third generation TKI with a median OS of 245 days (95% CI: 215.48–274.52) versus 52 days (95% CI: 22.62–81.38) in favour of third generation TKI. 22 Similar dismal median OS of 3 months was reported in breast cancer patients from Thiruvananthapuram (State of Kerala). 23 …”

“…In a large experience from prospective studies in NSCLC, the symptoms of leptomeningeal disease were symptoms of altered higher mental functions (48.4%) or seizures and Headache and dizziness (32.2%). 22 Similar experience was published from Kochi, where the commonest presenting features were headache, vomiting, loss of consciousness, cranial nerve palsies and seizures. 21 …”

“…In a LMC experience reported from Kochi (State of Kerala), the commonest site leading to LMC was breast (45%) followed by lung cancer (35%). 21 Other large experiences from India (>1100 patients) by Patil and colleagues 22 and Abraham and colleagues, 23 were in lung cancer and breast cancer respectively.…”