There is a critical need for effective treatments for leptomeningeal disease (LMD). Here, we report the interim analysis results of an ongoing single-arm, first-in-human phase 1/1b study of concurrent intrathecal (IT) and intravenous (IV) nivolumab in patients with melanoma and LMD. The primary endpoints are determination of safety and the recommended IT nivolumab dose. The secondary endpoint is overall survival (OS). Patients are treated with IT nivolumab alone in cycle 1 and IV nivolumab is included in subsequent cycles. We treated 25 patients with metastatic melanoma using 5, 10, 20 and 50 mg of IT nivolumab. There were no dose-limiting toxicities at any dose level. The recommended IT dose of nivolumab is 50 mg (with IV nivolumab 240 mg) every 2 weeks. Median OS was 4.9 months, with 44% and 26% OS rates at 26 and 52 weeks, respectively. These initial results suggest that concurrent IT and IV nivolumab is safe and feasible with potential efficacy in patients with melanoma LMD, including in patients who had previously received anti-PD1 therapy. Accrual to the study continues, including in patients with lung cancer. ClinicalTrials.gov registration: NCT03025256.

Polypyrimidine tract-binding protein (PTB) is a nuclear factor that binds to the polypyrimidine tract of premRNA introns, where it is associated with

With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority. While consensus guidelines recommend surgery followed by stereotactic radiosurgery (SRS) for lesions >3 cm, smaller lesions (≤3 cm) treated with SRS alone elicit variable responses. To determine factors influencing this variable response to SRS, we analyzed outcomes of brain metastases ≤3 cm diameter in patients with no prior systemic therapy treated with frame-based single-fraction SRS. Following SRS, 259 out of 1733 (15%) treated lesions demonstrated MRI findings concerning for local treatment failure (LTF), of which 202 /1733 (12%) demonstrated LTF and 54/1733 (3%) had an adverse radiation effect. Multivariate analysis demonstrated tumor size (>1.5 cm) and melanoma histology were associated with higher LTF rates. Our results demonstrate that brain metastases ≤3 cm are not uniformly responsive to SRS and suggest that prospective studies to evaluate the effect of SRS alone or in combination with surgery on brain metastases ≤3 cm matched by tumor size and histology are warranted. These studies will help establish multi-disciplinary treatment guidelines that improve local control while minimizing radiation necrosis during treatment of brain metastasis ≤3 cm.

OBJECTIVE: Metastasis to the spinal cord is rare, and optimal management of this disease is unclear. The authors investigated this issue by analyzing the results of surgical treatment of spinal intramedullary metastasis (IM) at a major cancer center.METHODS: The authors retrospectively reviewed the medical records of 13 patients who underwent surgery for IM. Patients had renal cell carcinoma (n = 4), breast carcinoma (n = 3), melanoma (n = 2), non–small cell lung cancer (n = 1), sarcoma (n = 1), adenoid cystic carcinoma (n = 1), and cervical cancer (n = 1). Cerebrospinal fluid was collected before surgery in 11 patients, and was negative for malignant cells, as was MRI of the neuraxis. Eleven patients presented with neurological function equivalent to Frankel Grade D.RESULTS: Radiographic gross-total resection was achieved in 9 patients, and tumor eventually recurred locally in 3 of those 9 (33%). Leptomeningeal disease was diagnosed in 4 patients after surgery. In the immediate postoperative period, neurological function in 6 patients deteriorated to Frankel Grade C. At 2 months, only 2 patients remained at Grade C, 8 were at Grade D, and 1 had improved to Grade E. One patient developed postoperative hematoma resulting in Frankel Grade A. Radiotherapy was delivered in 8 patients postoperatively. The median survival after spine surgery was 6.5 months. Three patients are still living.CONCLUSIONS: Surgery was performed as a last option to preserve neurological function in patients with IM. In most patients, neurological function returned during the immediate postoperative period and was preserved for the patients’ remaining lifetime. The data suggest that surgery can be effective in preventing further decline in selected patients with progressive neurological deficit.