Clinical outcomes and quality of life in children and adolescents with primary brain tumors treated with pencil beam scanning proton therapy.

BACKGROUND: Long-term treatment-related toxicity may substantially impact well-being, quality of life (QoL), and health of children/adolescents with brain tumors (CBTs). Strategies to reduce toxicity include pencil beam scanning (PBS) proton therapy (PT). This study aims to report clinical outcomes and QoL in PBS-treated CBTs. PROCEDURE: We retrospectively reviewed 221 PBS-treated CBTs aged <18 years. Overall-free (OS), disease-free (DFS), and late-toxicity-free survivals (TFS), local control (LC) and distant (DC) brain/spinal control were calculated using Kaplan-Meier estimates. Prospective QoL reports from 206 patients (proxies only ≤4 years old [yo], proxies and patients ≥5 yo) were descriptively analyzed. Median follow-up was 51 months (range, 4-222). RESULTS: Median age at diagnosis was 3.1 years (range, 0.3-17.7). The main histologies were ependymoma (n = 88; 39.8%), glioma (n = 37; 16.7%), craniopharyngioma (n = 22; 10.0%), atypical teratoid/rhabdoid tumor (ATRT) (n = 21; 9.5%) and medulloblastoma (n = 15; 6.8%). One hundred sixty (72.4%) patients received chemotherapy. Median PT dose was 54 Gy(relative biological effectiveness) (range, 18.0-64.8). The 5-year OS, DFS, LC, and DC (95% CI) were 79.9% (74-85.8), 65.2% (59.8-70.6), 72.1% (65.4-78.8), and 81.8% (76.3-87.3), respectively. Late PT-related ≥G3 toxicity occurred in 19 (8.6%) patients. The 5-year ≥G3 TFS was 91.0% (86.3-95.7). Three (1.4%) secondary malignancies were observed. Patients aged ≤3 years at PT (P = .044) or receiving chemotherapy (P = .043) experienced more ≥G3 toxicity. ATRT histology independently predicted distant brain failure (P = .046) and death (P = .01). Patients aged ≥5 years self-rated QoL higher than their parents (proxy assessment). Both reported lower social functioning and cognition after PT than at baseline, but near-normal long-term global well-being. QoL was well below normal before and after PT in children ≤4 years. CONCLUSIONS: The outcome of CBTs was excellent after PBS. Few patients had late ≥G3 toxicity. Patients aged <5 years showed worse QoL and toxicity outcomes.

Prognostic impact of the "Sekhar grading system for cranial Chordomas" in patients treated with pencil beam scanning proton therapy: an institutional analysis.

BACKGROUND: Skull base chordomas are rare and heterogeneously behaving tumors. Though still classified as benign they can grow rapidly, are locally aggressive, and have the potential to metastasize. To adapt the treatment to the specific needs of patients at higher risk of recurrence, a pre-proton therapy prognostic grading system would be useful. The aim of this retrospective analysis is to assess prognostic factors and the "Sekhar Grading System for Cranial Chordomas" (SGSCC) by evaluating the larger cohort of patients treated at our institution as to determine its reproducibility and ultimately to ensure more risk adapted local treatments for these challenging tumors. METHODS: We analyzed 142 patients treated for skull base chordomas between 2004 and 2016. We focused the analysis on the 5 criteria proposed for the SGSCC (tumor size, number of anatomic regions and vessels involved, intradural invasion, as well as recurrence after prior treatment) and classified our patients according to their score (based on the above mentioned criteria) into three prognostic groups, low-risk, intermediate-risk and high-risk. The three groups were then analyzed in regards of local control, local recurrence-free survival and overall survival. RESULTS: The median follow up was 52 months (range, 3-152). We observed 34 (24%) patients with a local recurrence, resulting in a local control of 75% at 5 years. Overall survival was 83% at 5 years, 12 (9%) patients had died due to local progression. When split into the three prognostic groups according to the SGSCC the observed local control was 90, 72 and 64% (p = 0.07) in the low-, intermediate- and high-risk group, respectively. A similar correlation was observed for local recurrence-free survival with 93, 89 and 66% (p = 0.05) and for overall survival with 89, 83 and 76% (p = 0.65) for the same prognostic groups. CONCLUSIONS: After splitting our patient cohort into the three SGSCC risk groups, we found a trend towards better outcome for those patients with lower as opposed to higher scores. These results suggest that this prognostic grading system published by Sekhar et al. could be integrated in the management decision-tree for patients with skull base chordoma.

Benchmarking a commercial proton therapy solution: The Paul Scherrer Institut experience.

OBJECTIVE: For the past 20 years, Paul Scherrer Institut (PSI) has treated more than 1500 patients with deep-seated tumors using PSI-Plan, an in-house developed treatment planning system (TPS) used for proton beam scanning proton therapy, in combination with its home-built gantries. The goal of the present work is to benchmark the performance of a new TPS/Gantry system for proton therapy centers which have established already a baseline standard of care. METHODS AND MATERIALS: A total of 31 cases (=52 plans) distributed around 7 anatomical sites and 12 indications were randomly selected and re-planned using Eclipse™. The resulting plans were compared with plans formerly optimized in PSI-Plan, in terms of target coverage, plan quality, organ-at-risk (OAR) sparing and number of delivered pencil beams. RESULTS: Our results show an improvement on target coverage and homogeneity when using Eclipse™ while PSI-Plan showed superior plan conformity. As for OAR sparing, both TPS achieved the clinical constraints. The number of pencil beams required per plan was on average 3.4 times higher for PSI-Plan. CONCLUSION: Both systems showed a good capacity to produce satisfactory plans, with Eclipse™ being able to achieve better target coverage and plan homogeneity without compromising OARs. ADVANCES IN KNOWLEDGE: A benchmark between a clinically tested and validated system with a commercial solution is of interest for emerging proton therapy, equipped with commercial systems and no previous experience with proton beam scanning.

Whole-ventricular irradiation for intracranial germ cell tumors: Dosimetric comparison of pencil beam scanned protons, intensity-modulated radiotherapy and volumetric-modulated arc therapy.

BACKGROUND: Whole-ventricular radiotherapy (WV-RT) followed by a boost to the tumor bed (WV-RT/TB) is recommended for intracranial germ cell tumors (IGCT). As the critical brain areas are mainly in the target volume vicinity, it is unclear if protons indeed substantially spare neurofunctional organs at risk (NOAR). Therefore, a dosimetric comparison study of WV-RT/TB was conducted to assess whether proton or photon radiotherapy achieves better NOAR sparing. METHODS: Eleven children with GCT received 24 Gy(RBE) WV-RT and a boost up to 40 Gy(RBE) in 25 fractions of 1.6 Gy(RBE) with pencil beam scanning proton therapy (PBS-PT). Intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans were generated for these patients. NOAR were delineated and treatment plans were compared for target volume coverage (TVC), homogeneity index (HI), inhomogeneity coefficient (IC) and (N)OAR sparing. RESULTS: TVC was comparable for all three modalities. Compared to IMRT and VMAT, PBS-PT showed statistically significant optimized IC, as well as dose reduction, among others, in mean and integral dose to the: normal brain (-35.2%, -32.7%; -35.2%, -33.0%, respectively), cerebellum (-53.7%, -33.1%; -53.6%, -32.7%) and right temporal lobe (-14.5%, -31.9%; -14.7%, -29.9%). The Willis' circle was better protected with PBS-PT than IMRT (-7.1%; -7.8%). The left hippocampus sparing was higher with IMRT. Compared to VMAT, the dose to the hippocampi, amygdalae and temporal lobes was significantly decreased in the IMRT plans. CONCLUSIONS: Dosimetric comparison of WV-RT/TB in IGCT suggests PBS-PT's advantage over photons in conformality and NOAR sparing, whereas IMRT's superiority over VMAT, thus potentially minimizing long-term sequelae.

Evaluation of the ray-casting analytical algorithm for pencil beam scanning proton therapy.

For pencil beam scanned (PBS) proton therapy, analytical dose calculation engines are still typically used for the optimisation process, and often for the final evaluation of the plan. Recently however, the suitability of analytical calculations for planning PBS treatments has been questioned. Conceptually, the two main approaches for these analytical dose calculations are the ray-casting (RC) and the pencil-beam (PB) method. In this study, we compare dose distributions and dosimetric indices, calculated on both the clinical dose calculation grid and as a function of dose grid resolution, to Monte Carlo (MC) calculations. The analysis is done using a comprehensive set of clinical plans which represent a wide choice of treatment sites. When analysing dose difference histograms for relative treatment plans, pencil beam calculations with double grid resolution perform best, with on average 97.7%/91.9% (RC), 97.9%/92.7% (RC, double grid resolution), 97.6%/91.0% (PB) and 98.6%/94.0% (PB, double grid resolution) of voxels agreeing within ±5%/± 3% between the analytical and the MC calculations. Even though these point-to-point dose comparison shows differences between analytical and MC calculations, for all algorithms, clinically relevant dosimetric indices agree within ±4% for the PTV and within ±5% for critical organs. While the clinical agreement depends on the treatment site, there is no substantial difference of indices between the different algorithms. The pencil-beam approach however comes at a higher computational cost than the ray-casting calculation. In conclusion, we would recommend using the ray-casting algorithm for fast dose optimization and subsequently combine it with one MC calculation to scale the absolute dose and assure the quality of the treatment plan.