Zhenyu Pan¹, Guozi Yang¹, Hua He², Lihua Dong¹

¹Department of Radiation Oncology, the First Hospital of Jilin University, ²Cancer Center, the First Hospital of Jilin University

Objective:The prognosis of leptomeningeal metastases (LM) from solid tumors is extremely poor, especially for patients with adverse prognostic factors. Previous studies indicate that intrathecal chemotherapy (IC) does not improve overall survival (OS) for patients with adverse prognostic factors. Involved-field radiotherapy (IF-RT) alone only alleviates symptoms of the nervous system with no survival benefit. This study combined IC concurrent with IF-RT for the treatment of LM from solid tumors with adverse prognostic factors. The objectives were to determine the efficacy of this treatment combination and the associated toxicity. Method: Fifty-three patients with LM from solid tumors were enrolled between September 2010 and May 2014. The regimen for concurrent therapy was simultaneous IC (MTX 12.5-15 mg and dexamethasone 5 mg, weekly) and IF-RT (whole brain RT 40 Gy/20fand/or spinal RT 40-50 Gy/20f). Inductive IC for 1-3 times was given followed by concurrent therapy for patients with low KPS score as well as intolerance to radiotherapy. All patients were followed up until October 2014. Primary endpoints were therapeutic response and toxicity. Secondary endpoint was OS. The evaluation of therapeutic response was according to the improvement of nervous system symptoms and KPS score. This study has been registered in the Chinese Clinical Trial Register (ChiCTR-OOC-14005403). Result: The pathological types included non-small cell lung cancer (26), small cell lung cancer (10), breast cancer (11), gastric cancer (4), hepatocellular carcinoma (1) and laryngeal cancer (1). Median KPS score was 40(range 20-70). Most patients (84.9%) completed the concurrent therapy. The overall response rate was 84.9% (45/53). Forty-three patients were dead by the end of follow-up. Survival ranged from 0.4 to 26.7 months (median 6.5). 1-year-survivalrate is 22%.The treatment-related adverse events consisted mainly of acute meningitis, chronic delayed encephalopathy, radiculitis, myelosuppression, and mucositis. Eleven patients (20.8%, 11/53) had grade III-V toxic reactions. Three patients died of neurotoxicity between 1.5-7 months after concurrent therapy. Conclusion:The regimen of concurrent therapy with significant activity and acceptable toxicity maybe an optimal therapeutic option for treatment of LM from solid tumors with adverse prognostic factors.

Key Words: leptomeningeal metastases  intrathecal chemotherapy