Extent of re-excision, sequence/timing of salvage re-irradiation, and disease-free interval impact upon clinical outcomes in recurrent/progressive ependymoma.

PURPOSE: To report clinical outcomes of salvage re-irradiation (re-RT) in recurrent/progressive ependymoma. METHODS: Medical records of patients treated with curative-intent re-RT as multi-modality management for recurrent/progressive ependymoma were analyzed retrospectively. The linear-quadratic model was used to provide estimates of biologically effective dose (BED) of irradiation using an α/ß value of 2 for late CNS toxicity for each course of irradiation and summated to derive cumulative BED without correcting for the assumed recovery. RESULTS: A total of 55 patients (median age 10 years at index diagnosis) treated with curative-intent re-RT between 2010 and 2018 were included. Median time to first recurrence was 29 months with an inter-quartile range (IQR) of 16-64 months. Majority (n = 46, 84%) of patients underwent surgical re-excision of recurrent disease. Median interval from first course of irradiation (RT1) to second course (RT2) was 35 months (IQR = 26-66 months) with a median re-RT dose of 54 Gy in 30 fractions (range 40-60 Gy), resulting in median cumulative equivalent dose in 2 Gy fraction (EQD2) of 106.2 Gy (range 92.4-117.6 Gy). Volume of re-RT was based on location and pattern of relapse, comprising uni-focal (n = 49, 89%), multi-focal (n = 3, 5.5%), or craniospinal irradiation (CSI) in 3 (5.5%) patients respectively. Thirty-six (66%) patients received platinum-based salvage chemotherapy either before or after RT2. At a median follow up of 37 months (range 6-80 months), the Kaplan-Meier estimates of 3-year progression-free survival (PFS) and overall survival (OS) for the entire study cohort were 40% and 51% respectively. Gross total resection at recurrence; early salvage re-RT (prior to chemotherapy, if any); and longer (> 2 years) disease-free interval (DFI) were associated with better survival outcomes. Salvage re-RT was generally well tolerated with only 3 (5.5%) patients developing symptomatic radiation necrosis necessitating corticosteroids. CONCLUSION: Extent of re-excision, sequence/timing of re-RT, and DFI impact upon outcomes in curative-intent, multi-modality salvage therapy for recurrent ependymoma.

Assessment of three-dimensional set-up errors using megavoltage computed tomography (MVCT) during image-guided intensity-modulated radiation therapy (IMRT) for craniospinal irradiation (CSI) on helical tomotherapy (HT).

The purpose of this study was to assess three-dimensional (3D) set-up errors using megavoltage computed tomography (MVCT) during image-guided intensity-modulated radiation therapy (IMRT) for supine craniospinal irradiation (CSI) on helical tomotherapy (HT). Patients were immobilized in a customized 4-clamp thermoplastic head mask with or without whole-body vacuum cradle. Set-up was based primarily on a set of cranial fiducial markers. MVCT scans were acquired and co-registered with planning scan separately at three different levels (brain, upper, and lower spine) at every fraction. Only translational displacements were analysed, wherein positive sign denotes deviation in anterior, left, and superior direction; while negative sign denotes deviation in posterior, right, and inferior direction. Mean displacements, systematic, and random errors of the study population were calculated at all three levels separately. Local residual uncertainty of the upper and lower spine was also derived assuming perfect co-registration of the skull. Set-up margins for clinical target volume (CTV) to planning target volume (PTV) were derived at these three levels separately using published margin recipes. Data from 1868 co-registrations in 674 fractions on 33 patients was included. The mean displacements in the lateral, longitudinal, and vertical directions were -1.21, -1.36, and 1.38 mm; -1.25, -0.34, and 0.65 mm; and -1.47, -2.78, and 0.22 mm for the brain; upper spine; and lumbar spine respectively. The corresponding 3D vector of displacement was 2.28; 1.45; and 3.15 mm respectively. There was a distinct systematic trend towards increasing inaccuracy from the brain towards the lower spine. Using Stroom's formula, the minimum recommended CTV to PTV margins in absence of daily image-guidance were 6.5; 7.0; and 9.5 mm for the brain; upper spine; and lower spine respectively. This increased to 7.5; 8.5; and 11.5 mm using van Herk's formula. Subset and sensitivity analyses could not identify any factor predictive of increased inaccuracy. Residual uncertainty of the spinal column was lesser after daily co-registration referenced to the skull, suggesting that smaller set-up margins maybe appropriate while using daily image-guidance with an online correction protocol. Daily MVCT imaging during supine CSI on HT provides volumetric verification of the set-up process. There is substantial site-dependent variability in translational displacements that increases systematically from brain towards the lower spine with implications for differential set-up -margins for the brain, upper, and lower spine.