Sener, Ugur T

Abstract Background The current treatment of glioblastoma involves resection followed by radiotherapy (RT) and temozolomide. Rapid early progression (REP) of tumor in the surgery-to-radiotherapy interval (SRI) has been described using categorical or semi-quantitative assessments and is associated with inferior clinical outcomes. This study seeks to establish and validate a quantitative definition for REP and examine how REP could inform future therapy. Methods Volumes of tumor and resection cavity at 3 time points—preoperative, postoperative and RT-planning (pre-RT)—were contoured among patients who had undergone standard of care. A minimal, but clinically appreciable, threshold for defining REP based on change in tumor volume was established, validated, and subsequently used to assess actionable predictors of REP and its prognostic value. Results An increase of >2 cc in volume or a new satellite tumor between the post-operative to planning MRI was found to be a sensitive, pragmatic, and statistically significant cutoff for REP (P = .002). Actionable predictors such as SRI of 6 weeks and a > 5 cc residual immediate post-operative tumor volume were found to be statistically significant predictors of REP. REP was also found to be a statistically significant prognostic indicator for overall survival (P = .002) and progression-free survival. Conclusion These findings support that an increase in tumor volume between post-operative and pre-RT MRI of >2 cc is the ideal working definition of REP in this clinical setting. Furthermore, REP could serve as a prognostic ­biomarker to track treatment response. Additionally, 2 actionable predictors of REP, post-op residual tumor volume and SRI, are identified.

Abstract Background This study aimed to determine whether proton craniospinal irradiation (CSI) decreased the dose to normal tissue and resulted in less toxicity than photon CSI for adult patients. Methods This single-institution retrospective analyzed differences in radiation doses, acute toxicity, and cost between proton and CSI for adult medulloblastoma patients. Results Of 39 total patients, 20 were treated with photon CSI prior to 2015, and 19 were treated with proton CSI thereafter. Median age was 28 years (range 18–66). The molecular subtype was most commonly sonic hedgehog (68%). Patients most commonly received 36 Gy CSI in 20 fractions with a boost to 54–55.8 Gy (92%). Proton CSI delivered significantly lower mean doses to cochleae, lacrimal glands, lens, parotid glands, pharyngeal constrictors, esophagus, lungs, liver, and skin (all P < .001). Patients receiving proton CSI had significantly lower rates of acute dysphagia of any grade (5% versus 35%, P = .044) and decreased median weight loss during radiation (+1.0 versus –2.8 kg, P = .011). Weight loss was associated with acute hospitalization (P = .009). Median follow-up was 2.9 and 12.9 years for proton and photon patients, respectively, limiting late toxicity and outcome comparisons. At the last follow-up, 5 photon patients had died (2 of progressive disease, 3 without recurrence ages 41–63) and 21% had experienced major cardiovascular events. At 10 years, 89% were alive and 82% were recurrence free. Conclusions This study demonstrates dosimetric improvements with proton CSI, potentially leading to decreased acute toxicity including dysphagia and weight loss during treatment.

Abstract Background Neurofibromatosis type 2 (NF2)-related schwannomatosis is an autosomal dominant tumor-predisposition syndrome characterized by bilateral vestibular schwannomas (VS). In patients with VS associated with NF2, vascular endothelial growth factor A inhibitor, bevacizumab, is a systemic treatment option. The aim of this study is to retrospectively evaluate NF2 patient responses to bevacizumab on VS growth and symptom progression. Methods This is a retrospective analysis of patients seen at the Mayo Clinic Rochester Multidisciplinary NF2 Clinic. Results Out of 76 patients with NF2 evaluated between 2020 and 2022, we identified 19 that received treatment with bevacizumab. Thirteen of these patients discontinued bevacizumab after median treatment duration of 12.2 months. The remaining 6 patients are currently receiving bevacizumab treatment for a median duration of 9.4 months as of March, 2023. Fifteen patients had evaluable brain MRI data, which demonstrated partial responses in 5 patients, stable disease in 8, and progression in 2. Within 6 months of bevacizumab discontinuation, 5 patients had rebound growth of their VS greater than 20% from their previous tumor volume, while 3 did not. Three patients with rebound growth went on to have surgery or irradiation for VS management. Conclusions Our single-institution experience confirms prior studies that bevacizumab can control progression of VS and symptoms associated with VS growth. However, we note that there is the potential for rapid VS growth following bevacizumab discontinuation, for which we propose heightened surveillance imaging and symptom monitoring for at least 6 months upon stopping anti-VEGF therapy.