Nivolumab for patients with recurrent glioblastoma progressing on bevacizumab: a retrospective case series.

A single institution retrospective evaluation of nivolumab following disease progression on bevacizumab in adults with recurrent glioblastoma (GBM) with an objective of determining progression free survival (PFS). There is no accepted therapy for recurrent GBM after failure of bevacizumab. 16 adults, ages 52-72 years (median 62), with recurrent GBM were treated. All patients had previously been treated with surgery, concurrent radiotherapy and temozolomide, and post-radiotherapy temozolomide. Bevacizumab (with or without lomustine) was administered to all patients at first recurrence. Patients were treated with nivolumab only (3 mg/kg) once every 2 weeks at second recurrence. One cycle of nivolumab was defined as 2 treatments. Neurological evaluation was performed bi-weekly and neuroradiographic assessment every 4 weeks. A total of 37 treatment cycles (median 2) were administered of nivolumab in which there were 14 Grade 2 adverse events (AEs) and Grade 3 AEs in two patients. No Grade 4 or 5 AEs were seen. Following 1 month of nivolumab, seven patients demonstrated progressive disease and discontinued therapy. No patient demonstrated a response though nine patients demonstrated neuroradiographic stable response. Survival in the entire cohort ranged from 2 to 6 months with a median of 3.5 months (CI 2.8, 4.2). Median and 6-month PFS at 6 months was 2.0 months (range 1-5 months; CI 1.3, 2.7) and 0% respectively. Nivolumab salvage therapy demonstrated no survival advantage in patients with recurrent bevacizumab refractory GBM emphasizing a continued unmet need in neuro-oncology.

Salvage therapy with bendamustine for temozolomide refractory recurrent anaplastic gliomas: a prospective phase II trial.

There is no standard therapy for recurrent anaplastic glioma (AG). Salvage therapies include alkylator-based chemotherapy, re-resection with or without carmustine implants, re-irradiation and bevacizumab. Bendamustine is a novel bifunctional alkylator with CNS penetration never previously evaluated in AG. Assess response and toxicity of bendamustine in recurrent AG in a phase II trial. Adults with radiation and temozolomide refractory recurrent AG were treated with bendamustine. A cycle of bendamustine was defined as two consecutive days of treatment (100 mg/m2/day) administered once every 4 weeks. Success of treatment was defined as progression free survival (PFS) at 6 months of 40 % or better. Twenty-six adults [16 males; 10 females: median age 40 years (range 30-65)] were treated, 12 at first recurrence and 17 at second recurrence. Prior salvage therapy included re-resection (14), chemotherapy (11) and re-radiation (2). Grade 3 treatment-related toxicities included lymphopenia (11 patients; Grade 4 in 3), myalgia, pneumonia, diarrhea, leukopenia, allergic reaction and thrombocytopenia in one patient each. One patient discontinued therapy due to toxicity. There were five instances of bendamustine dose delays all due to lymphopenia. There were no dose reductions due to toxicity. The median number of cycles of therapy was 3 (range 1-8). Best radiographic response was progressive disease in 12 (46 %), stable disease in 13 (50 %) and partial response in 1 (4 %). Median, 6- and 12-month PFS was 2.7 months (range 1-52), 27 and 8 % respectively. In patients with recurrent AG refractory to Z, bendamustine has manageable toxicity and modest single agent activity though not meeting pre-specified study criteria.

Hiatal Herniation After Transhiatal Esophagectomy: an Underreported Complication.

INTRODUCTION: The incidence and presentation of hiatal hernias after esophagectomy (HHAE) are not well characterized, and may be changing with increased survival from esophageal cancer. The aims of this study were to define the incidence and presentation of HHAE in our population of patients undergoing transhiatal esophagectomy (THE), as it may have implications for management. METHODS: A retrospective cohort study (2004-2013) was performed of esophageal cancer patients who underwent THE. To determine the presence or absence of HHAE independent of the original radiology report, a radiologist sub-specializing in body imaging independently reviewed post-operative computed tomography images. A time-to-event competing risk analysis was performed to estimate the cumulative incidence of HHAE. RESULTS: Among 192 patients, the two-year cumulative incidence of HHAE was 14 % (95 % confidence interval 7.5-21 %). Of the 22 patients determined to have HHAE by independent expert radiologist review, only 11 (50 %) were identified by the original interpreting radiologist. Seven patients were symptomatic, and each underwent hiatal hernia repair (4 via laparotomy, 3 via laparoscopy). CONCLUSION: HHAE is not rare and is often unrecognized. As more patients with esophageal cancer survive, the number of patients becoming symptomatic and requiring repair may also rise. Therefore, it is important to consider this diagnosis when following patients long-term after esophagectomy.