Objective The immune modulatory drug chloroquine (CQ) has been demonstrated to enhance survival following radiotherapy in patients with high-grade glioma in a clinical trial, but the efficacy in patients with brain metastases is unknown. We hypothesized that short-course CQ during whole brain radiotherapy (WBRT) would improve response to local therapy in patients with brain metastases. Methods A prospective, single-cohort study was performed combining WBRT with concurrent CQ to assess both the feasibility of and intracranial response to combined therapy in patients with brain metastases. Safety, tolerability and overall survival of this combination was also examined, along with allelic status of IDO2 (indoleamine 2,3-dioxygenase 2), an immune modulatory enzyme inhibited by chloroquine that may affect survival outcomes. CQ therapy (250 mg by mouth daily) was initiated 1 week before WBRT (37.5 Gy in 2.5 Gy daily fractions) in patients with newly diagnosed brain metastases from biopsy-proven, primary lung, breast or ovarian solid tumors (n=20). The primary endpoint was radiologic response 3 months after combined CQ and WBRT therapy. Secondary endpoints included toxicity and overall survival. Patients were stratified by IDO2 allelic status. Results After a median clinical follow up of 5 months (range, 0.5–31), 16 patients were evaluable for radiologic response which was complete response in two patients, partial response in 13 patients and stable disease in one patient. There were no treatment-related grade≥3 toxicities or treatment interruption due to toxicity. Median and mean overall survival was 5.7 and 8.9 months, respectively (range, 0.8–31). A trend toward increased overall survival was observed in patients with wild-type IDO2 compared to patients with heterozygous or homozygous configurations that ablate IDO2 enzyme activity (10.4 mos vs. 4.1 mos.; p=0.07). Conclusions WBRT with concurrent, short-course CQ is well tolerated in patients with brain metastases. The high intracranial disease control rate warrants additional study.

BackgroundSkull base meningiomas commonly present with cranial neuropathies. Fractionated stereotactic radiation therapy (FSRT) has been used to treat these tumors with excellent local control, but rates of improvement in cranial neuropathies have not been well defined. We review the experience at Thomas Jefferson University using FSRT in the management of these patients with a focus on symptom outcomes.MethodsWe identified 225 cases of skull base meningiomas treated with FSRT at Thomas Jefferson University from 1994 through 2009. The target volume was the enhancing tumor, treated to a standard prescription dose of 54 Gy. Symptoms at the time of RT were classified based on the cranial nerve affected. Logistic regression was performed to determine predictors of symptom improvement after FSRT.ResultsThe median follow-up time was 4.4 years. In 92% of cases, patients were symptomatic at the time of RT; the most common were impaired visual field/acuity (58%) or extraocular movements (34%). After FSRT, durable improvement of at least one symptom occurred in 57% of cases, including 40% of visual acuity/visual field deficits, and 40% of diplopia/ptosis deficits. Of all symptomatic patients, 27% experienced improvement of at least one symptom within 2 months of the end of RT.ConclusionsFSRT is very effective in achieving improvement of cranial neuropathies from skull base meningiomas, particularly visual symptoms. Over half of treated patients experience a durable improvement of at least one symptom, frequently within 2 months from the end of RT.