Search

Purpose: The physical properties of protons lower doses to surrounding normal tissues compared with photons, potentially reducing acute and long-term adverse effects, including subsequent cancers. The magnitude of benefit is uncertain, however, and currently based largely on modeling studies. Despite the paucity of directly comparative data, the number of proton centers and patients are expanding exponentially. Direct studies of the potential risks and benefits are needed in children, who have the highest risk of radiation-related subsequent cancers. The Pediatric Proton and Photon Therapy Comparison Cohort aims to meet this need., Methods and Materials: We are developing a record-linkage cohort of 10,000 proton and 10,000 photon therapy patients treated from 2007 to 2022 in the United States and Canada for pediatric central nervous system tumors, sarcomas, Hodgkin lymphoma, or neuroblastoma, the pediatric tumors most frequently treated with protons. Exposure assessment will be based on state-of-the-art dosimetry facilitated by collection of electronic radiation records for all eligible patients. Subsequent cancers and mortality will be ascertained by linkage to state and provincial cancer registries in the United States and Canada, respectively. The primary analysis will examine subsequent cancer risk after proton therapy compared with photon therapy, adjusting for potential confounders and accounting for competing risks., Results: For the primary aim comparing overall subsequent cancer rates between proton and photon therapy, we estimated that with 10,000 patients in each treatment group there would be 80% power to detect a relative risk of 0.8 assuming a cumulative incidence of subsequent cancers of 2.5% by 15 years after diagnosis. To date, 9 institutions have joined the cohort and initiated data collection; additional centers will be added in the coming year(s)., Conclusions: Our findings will affect clinical practice for pediatric patients with cancer by providing the first large-scale systematic comparison of the risk of subsequent cancers from proton compared with photon therapy., Competing Interests: Matthew M. Mille reports sponsored travel to scientific meetings. Daniel J. Indelicato received a grant from the National Cancer Institute within the past 36 months for participation on the National Cancer Institute Pediatric Clinical Institutional Review Board. Joshua D. Palmer received research grants from Varian Medical Systems, The Kroger Company, Genentech, and the National Institutes of Health, consultant fees from Huron Consulting, a speaker honorarium from Varian Medical Systems, and travel support from Novocure and Varian Medical Systems, and is a Novocure Advisory Board member. Sujith Baliga received a speaker honorarium from Varian Medical Center. Matthew M. Poppe received a speaker honorarium and travel support from Mevion and is an investor in PEEL Therapeutics. Derek S. Tsang is a consultant for Back Alley Film Productions, MD lawyers and received meeting registration support from Mevion Medical Systems. Torunn I. Yock received in-kind research support from MIM Software, Inc. No other disclosures were reported.

Purpose: The aim of this study was to comprehensively review all studies examining clinical outcomes of craniospinal irradiation with proton radiotherapy for medulloblastoma (MB) to determine whether theoretical dosimetric advantages have translated into superior clinical outcomes (including survival and toxicities) compared with traditional photon-based techniques., Methods and Materials: We performed a systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles reporting on clinical outcomes of pediatric and/or adult patients with MB treated with proton radiotherapy were included. Evidence quality was assessed using a modified Newcastle Ottawa scale and GRADE score., Results: Thirty-five studies were included, with a total of 2059 patients reported (representing an estimated 630-654 unique patients). None of the studies were randomized, 12 were comparative, 9 were prospective, 3 were mixed, and 22 were retrospective. Average mean/median follow-up was 5.0 years (range, 4 weeks to 12.6 years). The majority of studies (n = 19) reported on treatment with passive scatter proton beams exclusively. Average study quality was 6.0 out of 9 (median, 6; standard deviation, 1.6). Nine studies scored ≥8 out of 9 on the modified Newcastle Ottawa Scale; an overall "moderate" GRADE score was assigned. Well-designed comparative cohort studies with adequate follow-up demonstrate superior neurocognitive outcomes, lower incidence of hypothyroidism (23% vs 69%), sex hormone deficiency (3% vs 19%), greater heights, and reduced acute toxicities in patients treated with protons compared to photons. Overall survival (up to 10 years), progression-free survival (up to 10 years), brain stem injury, and other endocrine outcomes were similar to those reported for photon radiation. There was insufficient evidence to make conclusions on endpoints of quality of life, ototoxicity, secondary malignancy, alopecia, scoliosis, cavernomas, and cerebral vasculopathy., Conclusions: Moderate-grade evidence supports proton radiotherapy as a preferred treatment for craniospinal irradiation of MB based on equivalent disease control and comparable-to-improved toxicity versus photon beam radiation therapy., (© 2023 The Author(s).)

Purpose: The contributory effects of radiation dose to different brain regions on neurocognitive performance after radiation therapy (RT) for primary brain tumors is not well known., Methods and Materials: In this retrospective cohort study, 30 patients with brain tumors treated with photon RT were identified, and radiation dosimetric parameters across brain regions were calculated. All patients had longitudinal neurocognitive evaluations at baseline and after treatment. Generalized estimating equations were used to model each neurocognitive endpoint over time in a multivariable analysis, while adjusted for multiple comparisons of brain regions., Results: Median follow-up from RT to last assessment was 4.1 years. Fewer years of formal education and older age at the time of RT were associated with lower scores in language, verbal memory, and working memory, after adjustment for baseline scores in multivariable analyses. Higher radiation dose to specific brain regions was not associated with declines in any of the evaluated cognitive domains. On average, there was no clinically significant decline (magnitude of z score change >1) between first and last neurocognitive evaluation. Across each individual cognitive domain, fewer than 15% of patients were impaired at most recent follow-up., Conclusions: In this small study of 30 patients treated with RT for a primary brain tumor, brain region dosimetry was not associated with decline in cognitive performance. Older age at time of RT and fewer years of formal education were associated with declines in cognitive performance, suggesting that effects of nondosimetric factors on cognitive performance should be considered alongside treatment factors and dosimetry in neuro-oncology research., (© 2022 The Author(s).)

Purpose: Reirradiation is rarely administered to patients with recurrent craniopharyngioma owing to concerns regarding visual and endocrine side effects. The purpose of this case series was to evaluate our institutional experience of patients with craniopharyngioma treated with 2 courses of fractionated radiation therapy., Methods and Materials: A retrospective study was performed of all patients with craniopharyngioma treated with 2 courses of fractionated radiation therapy at a single institution. Electronic medical records and radiation therapy records were reviewed., Results: We identified 4 eligible patients with recurrent craniopharyngioma. With a median follow-up of 33 months after reirradiation, 3 patients attained disease control; 1 patient developed progressive disease, 27 months after reirradiation. In 3 evaluable patients, vision remained stable or improved after reirradiation; one patient had no light perception before reirradiation. None of the patients experienced additional endocrine toxicities after reirradiation, apart from one patient who had low serum thyroid stimulating hormone before reirradiation and later developed hypothyroidism after treatment., Conclusions: Reirradiation may represent a safe and effective therapeutic option for selected patients with recurrent, refractory craniopharyngioma and without other salvage treatment options. Larger studies with longer-term follow up are warranted to better understand outcomes in these patients., (© 2020 The Authors.)