Megan Mackey

Phase II Trial of Single-Agent Bevacizumab Followed by Bevacizumab Plus Irinotecan at Tumor Progression in Recurrent Glioblastoma

PURPOSE To evaluate single-agent activity of bevacizumab in patients with recurrent glioblastoma. PATIENTS AND METHODS Patients with recurrent glioblastoma were treated with bevacizumab 10 mg/kg every 2 weeks. After tumor progression, patients were immediately treated with bevacizumab in combination with irinotecan 340 mg/m(2) or 125 mg/m(2) every 2 weeks, depending on use of enzyme-inducing antiepileptic drugs. Complete patient evaluations were repeated every 4 weeks. RESULTS Forty-eight heavily pretreated patients were accrued to this study. Thromboembolic events (12.5%), hypertension (12.5%), hypophosphatemia (6%), and thrombocytopenia (6%) were the most common drug-associated adverse events. Six patients (12.5%) were removed from study for drug-associated toxicity (five thromboembolic events, one bowel perforation). Thirty-four patients (71%) and 17 patients (35%) achieved radiographic response based on Levin and Macdonald criteria, respectively. Median progression-free survival (PFS) was 16 weeks (95% CI, 12 to 26 weeks). The 6-month PFS was 29% (95% CI, 18% to 48%). The 6-month overall survival was 57% (95% CI, 44% to 75%). Median overall survival was 31 weeks (95% CI, 21 to 54 weeks). Early magnetic resonance imaging response (first 96 hours and 4 weeks) was predictive of long-term PFS, with the Levin criteria being more predictive than Macdonald criteria. Of 19 patients treated with bevacizumab plus irinotecan at progression, there were no objective radiographic responses. Eighteen patients (95%) experienced disease progression by the second cycle, and the median PFS was 30 days. CONCLUSION We conclude that single-agent bevacizumab has significant biologic and antiglioma activity in patients with recurrent glioblastoma.

Abstract 1433: A mobile app for health related quality of life and symptom assessment in patients with primary brain tumors in an outpatient oncology clinic

Purpose: Primary brain tumors, and their treatments, can have a significant impact on patient quality of life due to altered mentation, mood changes, memory loss, and neurologic deficits. It has therefore been suggested that patient related outcomes need to be included as endpoints for treatment efficacy. The objective of this project was to develop and evaluate a mobile application (GlioNCI), in reporting health-related quality of life measures and symptom scoring in patients with primary brain tumors treated and followed in an outpatient oncology clinic. Experimental Procedures and Results: Apple9s Xcode Integrated Development Environment (IDE) was used to develop GlioNCI using the Swift programming language. The parameters and scores chosen had previously been validated in primary CNS tumors. Medication and steroid use is captured at each encounter, as are seizure characteristics, frequency and management. Health related quality of life questionnaires included portions of the EORTC QLQ-C30, and EORTC QLQ-BN20, and MD Anderson Symptom Inventory Brain Tumor Module, which have been validated in patients with cancer and primary CNS tumors respectively. Patients’ symptoms and effects on function are collected with the Activities of Daily Living scale, and the Instrumental Activities of Daily Living Scale. Mood and mental state were addressed using the Hospital Anxiety and Depression Scale. Separate questionnaires for different encounters and time points in outpatient treatment were included to assess care provider, as well as patient related measures, allowing for flexibility of the app to the needs of both. A mobile app was developed to collect, and archive in a database, input and feedback from both patients and care providers in oncology clinics. Conclusion: The creation of a patient centered quality of life and symptom assessment mobile app, following patients with primary brain tumors over their course of treatment and in follow-up is feasible. Pilot testing and patient evaluation of the application in an oncology clinic will be used to validate GlioNCI as a tool in outpatient clinics. Citation Format: Lindsay Rowe, Tuo Dong, Terri Armstrong, Megan Mackey, Mark Gilbert, Andra Krauze, Kevin Camphausen. A mobile app for health related quality of life and symptom assessment in patients with primary brain tumors in an outpatient oncology clinic. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1433.

Late toxicity in long-term survivors from a phase 2 study of concurrent radiation therapy, temozolomide and valproic acid for newly diagnosed glioblastoma

Background Valproic acid (VPA) is an antiepileptic agent with histone deacetylase inhibitor activity shown to enhance overall survival and progression free survival in patients with newly diagnosed glioblastoma (GBM). This reports on the late toxicity of the VPA/radiotherapy (RT)/temozolomide (TMZ) combination in the long-term survivors of a phase 2 study evaluating this regimen. Methods 37 patients with newly diagnosed GBM were initially enrolled on this trial and received combination therapy. VPA/RT/TMZ related late toxicities were evaluated in the 6 patients that lived greater than 3 years using the Cancer Therapy and Evaluation Program Common Toxicity Criteria (CTC) Version 4.0 for toxicity and adverse event reporting as well as the RTOG/EORTC Radiation Morbidity Scoring Scheme. Results The median duration of follow-up for these 6 patients was 69.5m. In this cohort, the median OS was 73.8m (60.8-103.8m) and median PFS was 53.1m (37.3 - 103.8m). The most common late toxicity of VPA in conjunction with RT/TMZ were the CTC classifications of neurological, pain, and blood/ bone marrow toxicity and most were grade 1/2. There were only two grade 3/4 toxicities. Conclusions The addition of VPA to concurrent RT/TMZ in patients with newly diagnosed GBM was well tolerated with little late toxicity. Additionally, VPA may result in improved outcomes as compared to historical data and merits further study.

Differentiating pseudoprogression from true progression: analysis of radiographic, biologic, and clinical clues in GBM

IntroductionPseudoprogression (PsP) is a diagnostic dilemma in glioblastoma (GBM) after chemoradiotherapy (CRT). Magnetic resonance imaging (MRI) features may fail to distinguish PsP from early true progression (eTP), however clinical findings may aid in their distinction.MethodsSixty-seven patients received CRT for GBM between 2003 and 2016, and had pre- and post-treatment imaging suitable for retrospective evaluation using RANO criteria. Patients with signs of progression within the first 12-weeks post-radiation (P-12) were selected. Lesions that improved or stabilized were defined as PsP, and lesions that progressed were defined as eTP.ResultsThe median follow up for all patients was 17.6 months. Signs of progression developed in 35/67 (52.2%) patients within P-12. Of these, 20/35 (57.1%) were subsequently defined as eTP and 15/35 (42.9%) as PsP. MRI demonstrated increased contrast enhancement in 84.2% of eTP and 100% of PsP, and elevated CBV in 73.7% for eTP and 93.3% for PsP. A decrease in FLAIR was not seen in eTP patients, but was seen in 26.7% PsP patients. Patients with eTP were significantly more likely to require increased steroid doses or suffer clinical decline than PsP patients (OR 4.89, 95% CI 1.003–19.27; p = 0.046). KPS declined in 25% with eTP and none of the PsP patients.ConclusionsMRI imaging did not differentiate eTP from PsP, however, KPS decline or need for increased steroids was significantly more common in eTP versus PsP. Investigation and standardization of clinical assessments in response criteria may help address the diagnostic dilemma of pseudoprogression after frontline treatment for GBM.