Allergies, atopy, immune-related factors and childhood rhabdomyosarcoma: a report from the Children's Oncology Group.

Rhabdomyosarcoma (RMS) is a highly malignant tumor of developing muscle that can occur anywhere in the body. Due to its rarity, relatively little is known about the epidemiology of RMS. Atopic disease is hypothesized to be protective against several malignancies; however, to our knowledge, there have been no assessments of atopy and childhood RMS. Therefore, we explored this association in a case-control study of 322 childhood RMS cases and 322 pair-matched controls. Cases were enrolled in a trial run by the Intergroup Rhabdomyosarcoma Study Group. Controls were matched to cases on race, sex and age. The following atopic conditions were assessed: allergies, asthma, eczema and hives; in addition, we examined other immune-related factors: birth order, day-care attendance and breastfeeding. Conditional logistic-regression models were used to calculate an odds ratio (OR) and 95% confidence interval (CI) for each exposure, adjusted for age, race, sex, household income and parental education. As the two most common histologic types of RMS are embryonal (n=215) and alveolar (n=66), we evaluated effect heterogeneity of these exposures. Allergies (OR=0.60, 95% CI: 0.41-0.87), hives (OR = 0.61, 95% CI: 0.38-0.97), day-care attendance (OR=0.48, 95% CI: 0.32-0.71) and breastfeeding for ≥ 12 months (OR=0.36, 95% CI: 0.18-0.70) were inversely associated with childhood RMS. These exposures did not display significant effect heterogeneity between histologic types (p>0.52 for all exposures). This is the first study indicating that atopic exposures may be protective against childhood RMS, suggesting additional studies are needed to evaluate the immune system's role in the development of this tumor.

Prospective, longitudinal comparison of neurocognitive change in pediatric brain tumor patients treated with proton radiotherapy versus surgery only.

BACKGROUND: Proton radiotherapy (PRT) reduces the volume of normal tissue receiving radiation dose, which may lead to better neurocognitive outcomes. We examined change in neurocognitive scores over time in pediatric brain tumor patients treated with proton craniospinal irradiation (CSI), proton focal RT, or surgery only. METHODS: Patients received annual neurocognitive evaluations for up to 6 years. We examined Full Scale IQ (FSIQ), Verbal Comprehension Index (VCI), Perceptual Reasoning Index (PRI), Working Memory Index (WMI), and Processing Speed Index (PSI) scores. General linear mixed models examined change in scores over time by treatment group, adjusting for significant covariates. RESULTS: Scores from 93 patients treated between 2012 and 2017 (22 proton CSI, 31 proton focal, and 40 surgery only) were examined. Treatment groups were similar on gender (51.6% male), age at treatment (median = 9.7 y), and length of follow-up (median = 2.9 y). The surgery only group had proportionately more gliomas (P < 0.001), and the proton CSI group had more infratentorial tumors (P = 0.001) and higher total RT dose (P = 0.004). The proton focal and surgery only groups exhibited stable neurocognitive scores over time across all indexes (all P > 0.05). In the proton CSI group, WMI, PSI, and FSIQ scores declined significantly (P = 0.036, 0.004, and 0.017, respectively), while VCI and PRI scores were stable (all P > 0.05). CONCLUSIONS: Focal PRT was associated with stable neurocognitive functioning into survivorship. Outcomes were similar whether patients received focal PRT or no radiotherapy, even in neurocognitive domains known to be particularly radiosensitive. Proton CSI emerged as a neurocognitive risk factor, consistent with photon outcomes research.

Ototoxicity and cochlear sparing in children with medulloblastoma: Proton vs. photon radiotherapy.

PURPOSE: To compare ototoxicity rates between medulloblastoma patients treated with protons vs. photons. MATERIALS AND METHODS: The study included 84 children diagnosed with medulloblastoma treated with either passively scattered protons (n = 38) or photons (n = 46). Patients underwent maximal safe resection followed by craniospinal irradiation, posterior fossa and/or tumor bed boost and chemotherapy according to one of 3 multi-institutional trials. Median audiogram follow-up was 56 months for protons and 66 months for photons. RESULTS: Mean cochlear dose (Dmc) was lower in patients treated with protons for both standard (p < 0.0001) and high-risk disease (p < 0.001). Grade 3 and 4 ototoxicity was seen in 7 of 75 (9.3%) and 9 of 91 (9.9%) ears (Brock, p = 0.91), 13 of 75 (17.3%) and 19 of 91 (20.9%) ears (POG, p = 0.56), and 15 of 75 (20.0%) and 21 of 91 (23.1%) ears (SIOP Boston, p = 0.63) with protons and photons respectively. CONCLUSIONS: While cochlear doses were lower in the proton group, patients treated with either protons or photons had similar Grade 3 and 4 ototoxicity rates.