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.

Early results and volumetric analysis after spot-scanning proton therapy with concomitant hyperthermia in large inoperable sacral chordomas.

OBJECTIVE: Large inoperable sacral chordomas show unsatisfactory local control rates even when treated with high dose proton therapy (PT). The aim of this study is assessing feasibility and reporting early results of patients treated with PT and concomitant hyperthermia (HT). METHODS:: Patients had histologically proven unresectable sacral chordomas and received 70 Gy (relative biological effectiveness) in 2.5 Gy fractions with concomitant weekly HT. Toxicity was assessed according to CTCAE_v4. A volumetric tumor response analysis was performed. RESULTS:: Five patients were treated with the combined approach. Median baseline tumor volume was 735 cc (range, 369-1142). All patients completed PT and received a median of 5 HT sessions (range, 2-6). Median follow-up was 18 months (range, 9-26). The volumetric analysis showed an objective response of all tumors (median shrinkage 46%; range, 9-72). All patients experienced acute Grade 2-3 local pain. One patient presented with a late Grade 3 iliac fracture. CONCLUSION: Combining PT and HT in large inoperable sacral chordomas is feasible and causes acceptable toxicity. Volumetric analysis shows promising early results, warranting confirmation in the framework of a prospective trial. ADVANCES IN KNOWLEDGE:: This is an encouraging first report of the feasibility and early results of concomitant HT and PT in treating inoperable sacral chordoma.

Radiation Necrosis and White Matter Lesions in Pediatric Patients With Brain Tumors Treated With Pencil Beam Scanning Proton Therapy.

PURPOSE: To assess the rate of radiation necrosis (RN) and white matter lesions (WMLs) in pediatric patients with primary brain tumors treated with pencil beam scanning (PBS) proton therapy (PT) with or without concomitant chemotherapy at the PSI. METHODS AND MATERIALS: Between 1999 and 2015, 171 pediatric patients (age <18 years) were treated with PT. Median age at diagnosis was 3.3 years (range, 0.3-17.0 years), and the median delivered dose was 54 Gy (relative biological effectiveness) (range, 40.0-74.1 Gy). Radiation necrosis and WMLs were defined as a new area of abnormal signal intensity on T2-weighted images or increased signal intensity on T2-weighted images, and contrast enhancement on T1 occurring in the brain parenchyma included in the radiation treatment field, which did not demonstrate any abnormality before PT. Radiation necrosis and WMLs were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up period for the surviving patients was 49.8 months (range, 5.9-194.7 months). RESULTS: Twenty-nine patients (17%) developed RN at a median time of 5 months (range, 1-26 months), most of them (n = 17; 59%) being asymptomatic (grade 1). Grade 2, 4, and 5 toxicities occurred in 8, 2, and 2 patients, respectively. Eighteen patients (11%) developed WMLs at a median time of 14.5 months (range, 2-62 months), most of them (n = 13; 72%) being asymptomatic (grade 1). White matter lesion grade 2 and 3 toxicities occurred in 4 and 1 patient(s), respectively. The 5-year RN-free and WML-free survival was 83% and 87%, respectively. In univariate analysis, neoadjuvant (P = .025) or any (P = .03) chemotherapy, hydrocephalus before PT (P = .035), and ependymoma (P = .026) histology were significant predictors of RN. CONCLUSIONS: Children treated with PT demonstrated a low prevalence of symptomatic RN (7%) or WML (3%) compared with similar cohorts treated with either proton or photon radiation therapy. Chemotherapy, ependymomal tumors and hydrocephalus as an initial symptom were significant risk factors for RN.

Tumour control and Quality of Life in children with rhabdomyosarcoma treated with pencil beam scanning proton therapy.

PURPOSE: To assess clinical outcomes in children with rhabdomyosarcoma (RMS) treated with pencil beam scanning (PBS) proton therapy (PT). METHODS AND MATERIALS: Eighty-three RMS (embryonal, n=74; 89%) patients treated between January 2000 and December 2014 were included. The median age was 4.5years (range, 0.8-15.5). All patients received systemic chemotherapy according to prospective protocols. Patients had low-, intermediate-, and high-risk disease in 24%, 63%, and 13% of cases, respectively. The median total dose delivered was 54Gy(RBE) (range, 41.4-64.8). RESULTS: After a median follow-up time of 55.5 months (range, 0.9-126.3), local failure occurred in 16 patients. The 5-year local-control survival rate was 78.5% [95% confidence interval (CI), 69.5-88.5%]. Significant predictors for local failure were group/stage, tumour location, and size. Fourteen patients (16%) died, all from tumour progression. The 5-year overall survival was 80.6% (95%CI, 71.8-90.0%). The 5-year incidence of grade 3 non-ocular late toxicity was 3.6% (95%CI, 1-12%). No grade 4-5 late toxicities were observed. One radiation-induced malignancy was observed (1.2%). The Quality of Life (QoL) scores increased significantly after PT compared to baseline values. CONCLUSIONS: PBS PT led to excellent outcome in children with RMS. Late non-ocular toxicity was minimal and QoL good.

Tumor control and QoL outcomes of very young children with atypical teratoid/rhabdoid tumor treated with focal only chemo-radiation therapy using pencil beam scanning proton therapy.

The aim of this analysis was to assess the early clinical results of pencil beam scanning proton therapy (PT) in the treatment of young children with non-metastatic atypical teratoid/rhabdoid tumor (ATRT) of the CNS. Fifteen children (male, n = 8, 53 %) were treated with PT between May 2008 and January 2013. Mean age at diagnosis was 17.4 ± 7.0 months. The localization was infratentorial in 9 (60 %) patients. Gross total resection of the primary tumors was achieved in 7 (47 %) patients. The dose administered focally under sedation was 54 Gy (RBE). After a median follow-up of 33.4 months (range 9.7-69.2), 3 (20 %), 4 (27 %) and 2 (13 %) patients presented with local failure (LF), distant brain failure (DBF) and spinal failure (SF), respectively. Six patients died, all of tumor progression. The 2-year overall- and progression-free survival was 64.6 and 66.0 %. Tumor location (supratentorial) and the extent of surgical resection (non-gross total resection) were negative prognostic factors for both OS and PFS. PT was well tolerated. No grade >2 acute toxicity was observed. The estimated 2-year toxicity-free survival was 90 %. As assessed by the PedsQoL proxy, no decrease in QoL was observed after PT. We conclude that PBS PT is an effective treatment for young children with ATRT. After PT, with or without concomitant chemotherapy, two third of the patients survived >2 years. Acute toxicity was manageable. Longer follow-up and larger numbers of patients are needed to assess long-term outcomes and treatment-induced toxicity.