Efficacy and Determinants of Adjuvant Radiation Therapy for Medulloblastoma Patients under 4: A Propensity Score Matched National Cohort Study of Survival Outcomes

Efficacy and Determinants of Adjuvant Radiation Therapy for Medulloblastoma Patients under 4: A Propensity Score Matched National Cohort Study of Survival Outcomes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Efficacy and Determinants of Adjuvant Radiation Therapy for Medulloblastoma Patients under 4: A Propensity Score Matched National Cohort Study of Survival Outcomes Shreyas Annagiri, Samuel Kim, Yusuke S. Hori, Justin Liu, Ahed Kattaa, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9361013/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Objective Medulloblastomas (MB) are the most common primary central nervous system malignancy in children (WHO Grade IV). While MB is commonly treated with cerebrospinal irradiation (CSI) in older children, potential neurodevelopmental complications have led to consideration of surgery and chemotherapy alone for children under 4. However, current guidelines lack a definitive recommendation for this patient population. We conducted a retrospective analysis of the SEERS 17 database (2000–2022) to investigate radiotherapy for MB patients under the age of 4. Methods 1:1 Propensity score matching (PSM) with a caliper of 0.03 was utilized to account for confounding variables. Kaplan Meier (KM) curves were computed for matched patients, followed by univariate cox survival analysis for both overall survival (OS) and cancer specific survival (CSS). A multivariate binomial regression model assessed determinants of radiation treatment selection. All statistical analyses were conducted using a significance threshold of α = 0.05. Results 375 patients under 4 with surgically resected MB were identified for analysis. The proportion receiving adjuvant radiation demonstrated a decrease with time (r=-0.77). Following PSM, 111 patients were identified for both the radiation treatment and no radiation treatment groups. KM analysis demonstrated no significant difference between the groups in CSS (p = 0.12) or OS (p = 0.063). The propensity score weighted Cox model demonstrated that radiation was associated with significantly improved OS (HR = 0.56, 95% CI 0.41–0.78, p = 0.0004) and improved CSS (HR = 0.57, 95% CI 0.40–0.80, p = 0.001), with consistent direction across both endpoints. In binomial regression, older age (β = 1.36, p < 0.001) and earlier year of diagnosis (β = − 0.08, p < 0.001) were associated with increased radiation receipt (Δ Deviance = 52.3, p < 0.001; AIC = 601.3). Conclusions Adjuvant radiation in MB patients under 4 was associated with improved OS. Radiation use for this population has decreased over time, with older age predicting greater treatment receipt. Prospective validation and reduced—dose radiation approaches are critical to ensure consistent survival benefit and minimal complications. medulloblastoma radiation therapy neurodevelopment gross total resection outcomes Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Medulloblastomas (MB) are the most common primary central nervous system malignancy in children (WHO Grade IV), composed of neuroepithelial cells most commonly seeding in the cerebellar vermis, hemisphere or the fourth ventricle of the brain. MBs are clinically heterogenous, classified by both histology and canonical molecular markers with well-defined differences in prognosis and incidence in children. The subtypes of MB include WNT activated MB, SHH activated MB, Group 3 MB, and Group 4 MB 1,2,3 . MBs are routinely treated with a combination of maximum obtainable surgical resection, chemotherapy and cerebrospinal irradiation (CSI) 4 , 5 , 6 , 7 , 8 . While treatment plans differ depending on indicated tumor progression, as well as known histological and molecular classifications, randomized control trials involving patients with MB have consistently demonstrated a survival benefit from adjuvant or post-surgical CSI. However, the role of adjuvant CSI as a mainstay treatment for infants and pediatric patients under the age of 3 remains opaque 9 . Although CSI may be efficacious in eliminating residual tumor growth and recurrence, potential neurotoxic and neurodevelopmental complications of radiation treatment may be exacerbated in younger patient populations 10 . Consequently, in the past decade, select institutions have opted to treat medulloblastoma cases in patients under the age of 3–4 with surgical resection and chemotherapy, avoiding CSI as a primary treatment modality and restricting its use to cases with extensive tumor proliferation or diffusion 11 . Additionally, recent stage III clinical trials have demonstrated the potential of reduced dose CSI as an alternative to traditional treatment regimens in young patients 12 . Of note, however, reduced dose CSI demonstrated worse survival in young medulloblastoma patients despite improved neurocognitive outcomes. Given the heterogeneity of results in the literature as demonstrated from single and multi-institutional studies, it has become increasingly necessary to determine the universality of the shift in the use of radiation therapy for medulloblastoma cases under the age of four and resultant differences in outcomes at the national level 13 , 14 . The Surveillance, Epidemiology and End Results (SEER) program from the National Cancer Institute is one of the most substantiative population-based tumor registries in the United States that enables the monitoring of cancer incidence and nationwide trends in cancer treatment 9 . The recent 2025 update to the SEERs registry ensures improved data quality and increased granularity of individual patient clinical details and treatment outcomes. To elucidate national patterns in radiation treatment for medulloblastoma cases under the age of 4, we conducted a retrospective analysis of the newly updated SEERs registry from 2000 to 2021. Methods The Surveillance, Epidemiology and End Results (SEERS) 17 database, a dataset of oncology cases diagnosed from 2000 to 2021 with time-dependent and county level indicators of socioeconomic status such as income and urbanization status, was utilized for analysis. The SEERS-17 database is sponsored by the National Cancer Institute and involves the collection of clinical and public health data from 17 different registries to monitor the incidence of cancer in various regions of the United States. The SEERS-17 database covers roughly 26% of the United States population and thus provides a large national sample size of clinical characteristics and outcomes in tumor patients. Through the SEERs*Stat software, the SEERS-17 database was queried for all cases with medulloblastoma (ICD 9470/3), receipt of chemotherapy, receipt of surgery, and age from 0 to 4 years. Cases which reported radiation treatment as ‘recommended, unknown if administered’, and ‘combination of beam with implants or isotopes’ were excluded from analysis. Cases where radiation treatment was given prior to surgical resection or where the sequence of surgery and radiation was unknown were excluded. Cases where radiation treatment was given intraoperatively or radiation treatment was given both before and after surgery were excluded to limit the radiation cohort to patients who received adjuvant radiation therapy. Extracted clinical characteristics included year of diagnosis, histology, primary site, cause of death, survival months, radiation treatment receipt, race/ethnicity, age group, and income status. This analysis utilized aggregation of certain clinical variables to account for low sample size attributed to the rarity of the tumor of interest. Race levels were aggregated to “Hispanic (All Races)”, “Non-Hispanic White” and “Non-Hispanic Minority” (composed of Asian/Pacific Islander, Black, Native American/Alaskan Native, and Unknown races). Annual income levels were aggregated for this analysis into levels $ 120k USD. Occipital and “overlapping region of the brain” primary sites were aggregated into the category “other” due to the low number of patients with tumors stemming from either site. The resulting aggregated levels for primary site included “Cerebellum”, “Brainstem”, “Brain, Unspecified”, “Ventricle” and “Other”. The histology variable contained levels of “Medulloblastoma, Unspecified”, “Large cell Medulloblastoma”, “WNT Activated Medulloblastoma”, “SHH activated Medulloblastoma”, and “Medulloblastoma, group 4”. Variable reference levels were standardized for all analyses. For radiation, the reference level indicated patients who received radiation treatment. For sex, the reference level indicated “Female”. For race, the reference level indicated “Non-Hispanic White”. For annual income, the reference level indicated the lowest class, or < $ 40k- $ 59,999 USD. For primary site, the reference level indicated “Ventricle”. The trend in proportion of cases over time for which radiation therapy was utilized was computed. A Chi-Square test for independence to determine differences in population demographics between radiation and no radiation cohort was conducted. 1:1 Propensity score matching (PSM) with a caliper of 0.03 was utilized to account for confounding variables, creating a matched cohort for causal analysis. Kaplan Meier (KM) curves were computed for matched patients assessing both overall survival (OS) and cancer specific survival (CSS). Univariate cox survival analysis for the matched patients was conducted to determine the impact of radiation receipt on OS and CSS. Finally, a multivariate binomial regression model with fixed effects of age, year of diagnosis, race, histology, primary site, and income was used to assess determinants of radiation receipt. All statistical analyses were conducted using the programming language R (version 4.4.0; R Foundation for Statistical Computing, Vienna, Austria) within the RStudio® environment (Posit Software, Boston, MA, USA), using a significance threshold of p = 0.05. Results Cohort Characteristics Prior to propensity score matching, 427 patients under the age of 4 with surgically resected medulloblastomas were identified for analysis. 53.1% of patients underwent beam radiation (n = 227), while 46.9% of patients had none or unknown radiation (n = 220). In the cohort of patients who underwent radiation, 54.6% were non-Hispanic white (n = 124), 29.5% were Hispanic (n = 67), and 15.9% were non-Hispanic minority (n = 36). 32.6% of this cohort was female (n = 74), while 67.4% (n = 153) was male. 3.1% (n = 7) of patients in this cohort were under 1 year of age, while 96.9%(n = 220) were between the age of 1 and 4 years. 87.2% (n = 198) of patients who underwent radiation were diagnosed with classical or unspecified medulloblastoma, 8.4% (n = 19) were diagnosed with large cell medulloblastoma, and 3.4% (n = 8) were diagnosed with group 4 medulloblastoma. This cohort additionally contained one patient who was diagnosed with WNT-activated medulloblastoma, and one patient who was diagnosed with SHH-activated medulloblastoma. In the cohort of patients who did not undergo radiation, 36.4% (n = 80) of patients were Hispanic, 48.6% (n = 107) were non-Hispanic White, and 15% (n = 33) were non-Hispanic minority. 34.5% (n = 76) of this cohort was female while 65.5% (n = 144) were male. 13.2% (n = 29) of these patients were under the age of 1 year, while 86.8% (n = 191) were between the ages of 1 and 4 years. 81.8% (n = 180) were diagnosed with classical or unspecific medulloblastoma, 7.3% (n = 16) were diagnosed with large cell medulloblastoma, and 10% (n = 22) were diagnosed with group 4 medulloblastoma. The non-radiation cohort contained one patient diagnosed with WNT-activated medulloblastoma and one patient diagnosed with SHH-activated medulloblastoma. The distribution of ages was statistically different between the radiation and no radiation cohort ( \(\:{\chi\:}^{2}\) , p < 0.05), while all other collected demographic variables demonstrated no significant difference between the two cohorts. [Table 1 ] Table 1 Patient Demographics Variable Radiation (n = 227) No/Unknown Radiation (n = 220) \(\:{\varvec{\chi\:}}^{2}\:\) P-Value Age category (%) p < 0.001 <1 year 7 (3.1%) 29 (13.2) 1–4 years 220 (96.9%) 191 (86.8%) Sex (%) 0.737 Female 74 (32.6%) 76 (34.5%) Male 153 (67.4%) 144 (65.5%) Race (%) 0.298 Hispanic (All Races) 67 (29.5%) 80 (36.4%) Non-Hispanic White 124 (54.6%) 107 (48.6%) Non-Hispanic Minority 36 (15.9%) 33 (15.0%) Histology (%) 0.110 Unspecified/Classical 198 (87.2%) 180 (81.8%) Large Cell 19 (8.4%) 16 (7.3%) Group 4 8 (3.5%) 22 (10.0%) WNT Activated 1 (0.4%) 1 (0.5%) SHH Activated 1 (0.4%) 1 (0.5%) Annual Income (%) 0.332 120k+ 10 (4.4%) 14 (6.4%) 90k-119k 76 (33.5%) 62 (28.5%) 60k-89k 121 (53.3%) 116 (52.7%) <40k – 59k 20 (8.8%) 28 (12.7%) P values were reported from a X 2 test for independence conducted for each variable. Trend in Radiation Receipt The trend in the proportion of surgically resected medulloblastoma cases under 4 years of age for which adjuvant radiation therapy was given demonstrated a decrease with time (r=-0.759) (Fig. 1 ). Propensity Score Matching Propensity Score matching across sex, primary site, race, income and histology resulted in a matched cohort of 142 patients. Plotting of standard mean differences (SMD) between patients of each treatment group prior to and following PSM demonstrated a well-balanced cohort, with SMDs between matched patients falling below a value of 0.1 (Fig. 2 ). PSM OS and CSS Kaplan Meier analysis for overall survival (OS) in the PSM cohort demonstrated a median OS of 267 days for patients who received radiation and 242 days for patients who did not receive radiation. Differences in survival approached significance (p = 0.056, log rank test) (Fig. 3 ). Kaplan Meier analysis for cancer specific survival (CSS) in the PSM demonstrated trends of improved survival with no significant difference observed (p = 0.098, log rank test) (Fig. 4 ). PSM Cox Regression for Overall Survival A univariate propensity score weighted cox regression for differences in overall survival determined by radiation receipt demonstrated significantly improved OS for patients who received radiation therapy (HR = 0.56, 95% CI 0.41–0.78, p = 0.0004). The cox regression model demonstrated moderate discrimination between survivors and non-survivors (concordance = 0.64) [Table 2 ]. The determined effect was supported by the Wald test (p = 0.0004), likelihood ratio test (p = 0.009), and robust score test (p = 0.0002). Table 2 Effect of Radiotherapy on Overall and Cancer-Specific Survival in Medulloblastoma (Propensity Score–Weighted Cox Analysis) Footnote : Hazard ratios were estimated using propensity score–weighted Cox proportional hazards models, stratified by matching subclass and using robust standard errors. Concordance indicates Harrell’s C index. Outcome N Events Comparison HR (95% CI) P-Value Concordance Overall Survival 284 106 Radiation vs No Radiation 0.56 (0.41–0.78) < 0.001 0.64 Cancer-Specific Survival 284 84 Radiation vs No Radiation 0.57 (0.40–0.80) < 0.001 0.64 PSM Cox Regression for Cancer Specific Survival A univariate propensity score weighted cox regression for differences in cancer specific survival determined by radiation receipt demonstrated significantly improved CSS for patients who received radiation therapy (HR = 0.57, 95% CI 0.40–0.80, p = 0.001). The cox regression model for CSS demonstrated equally competent discriminative ability between survivors and non-survivors as the OS model (concordance = 0.64) [Table 2 ]. The determined effect on CSS was further supported by the Wald test (p = 0.001), robust score test (p = 0.0007), and likelihood ratio test (p = 0.02). Determinants of Radiation Treatment Through multivariate binomial logistic regression analysis, significant clinical characteristics associated with radiation treatment compared to no radiation treatment were assessed. Older age(β = 1.36, p < 0.001) and earlier year of diagnosis (β = − 0.08, p < 0.001) were associated with increased radiation receipt. Inclusion of covariates significantly improved model fit (Δ Deviance = 52.3, p < 0.001; AIC = 601.3) [Table 3 ]. Table 3 Binomial logistic regression analysis of factors associated with receipt of adjuvant radiation therapy in MB Variable Odds Ratio 95% CI (OR) P-Value Year of Diagnosis d 0.923 0.891–0.956 < 0.001 Age d 3.912 2.163–7.738 < 0.001 Sex Female ᵃ Reference Reference Reference Male 1.113 0.729–1.699 0.619 Race White ᵃ Reference Reference Reference Hispanic (All Races) 0.757 0.479–1.193 0.232 Non-Hispanic Minority 1.081 0.603–1.946 0.794 Income 40k-59,999 ᵃ Reference Reference Reference 60k – 89,999 1.393 0.715–2.750 0.332 90k – 119,999 1.669 0.824–3.420 0.157 120k+ 1.311 0.441–3.844 0.621 Medulloblastoma Type Classical (NOS) Reference Reference Reference Large cell 1.150 0.547–2.449 0.712 Group 4 0.596 0.223–1.470 0.277 WNT-Activated 1.876 0.071–49.87 0.665 SHH-Activated 1.875 0.070–49.69 0.664 Primary Site Ventricle Reference Reference Reference Cerebellum 0.513 0.164–1.499 0.230 Brain Stem 0.579 0.169–1.876 0.369 Brain, NOS 0.492 0.124–1.852 0.299 Other 0.493 0.036–12.42 0.603 a Reference category, b p < 0.05, c p < 0.01, d p < 0.001, Odds ratios and 95% confidence intervals are reported for each covariate, the outcome variable was receipt of adjuvant radiation therapy (yes vs. no). ᵃ Discussion National trends for CSI in children under 4 years of age for medulloblastoma have decreased year-by-year (r = − 0.759, p < 0.001). This is likely attributable to the continued controversy surrounding the use of CSI in infants and young children because of its acute and long-term toxicities 16 . Our study suggests that the therapeutic sequelae has largely discouraged the use of CSI in pediatric medulloblastoma. Indeed, age correlated positively with irradiation patterns on multivariable analysis (p < 0.001), suggesting that toxicity, particularly in infants, dissuades clinicians from utilizing CSI to treat pediatric medulloblastoma in the very young. This is consistent with current advancements in clinical trials for the very young and the appropriate avoidance of late neurocognitive effects 17 , 18 , 19 , 20 , 21 , 22 . Temporal trends for increasingly lower rates of CSI for pediatric medulloblastoma were also confirmed on multivariable analysis. Still, CSI improved CSS and OS in our propensity-score weighted models. While Kaplan Meier models demonstrated only marginal effects, CSI was associated with an approximately 43% decrease in relative risk for overall survival and cancer specific mortality in our cohort as modelled by cox proportional hazards. Additionally, previous clinical trials have demonstrated survival benefits from standard dose CSI as opposed to lose dose CSI 12 . These survival outcomes suggest the CSI remains largely therapeutic, although the year-by-year variability of the very young tends to create discourse in the use of CSI for medulloblastoma. This follows evidence for the efficacy of CSI in whole-group analysis 23 , 24 . Overall, frontline and salvage CSI is a considerable therapy for infant and young childhood medulloblastoma 25 . Although our study did not consider frontline versus salvage irradiation, our study found that CSI improved survival in line with the recent literature 26 , 27 . National trends suggest that the use of CSI continues to be controversial due to the profound late effects including neurocognitive and development delay 26 , 28 . These decisions seemingly exist despite evidence to support survival penalties in delayed or excluded CSI therapy in the very young 29 . Recent efforts to stratify pediatric medulloblastoma by molecular traits have helped reduce radiotherapy while maintaining survival benefits through chemotherapy alone 11 , 30 . Our study suggests that molecular subtyping and the preference for reduced radiotherapy convention is increasing, with more evidence for effective management utilizing genomic data in infant and very young pathology 31 . Our group did not subcategorize for the molecular markers of pediatric medulloblastoma in order to protect the power of the statistical analyses. However, radiotherapy and chemotherapy trends likely differ between histological and molecular subtypes, and future research should explore trends in clinical decision-making across molecular subtypes. Immunotherapy for pediatric and adult medulloblastoma has likely changed the landscape of clinical practice, as well. Immunotherapy for infantile medulloblastoma opens the door for improved survival while mitigating the drastic effects of chemoradiotherapy. A recent Phase II study has found benefits for primary and relapse medulloblastoma utilizing combined monoclonal antibodies and radiotherapy 32 . Other studies have demonstrated the possible efficacy of oncolytic viruses for increasing cell recognition of medulloblastoma antigens 33 . Clinical trials are currently underway exploring the use of viruses for the therapy of medulloblastoma with hopes of immune reactivity unlike more T-cell exhausted tumors like glioblastoma. However, current evidence from vaccine therapy demonstrates considerable immunosuppressive behavior in medulloblastoma 34 , with special considerations in infantile medulloblastoma and the naive immune system. Even so, continued work to identify molecular and genetic signatures in medulloblastoma and to understand the tumor immune microenvironment has unlocked new possibilities regarding therapeutic strategies and precision medicine 35 . Ultimately, the use of CSI will continue to decrease in the treatment of infantile and very young medulloblastoma with a greater emphasis on chemotherapy alone recommendations 36 . Rescue CSI may always be necessary for particular subtypes or behaviors of medulloblastoma, and consistent survival benefits are noted for OS and CSS in this study. However, our study did not differentiate between molecular subtypes and, furthermore, did not evaluate for radiotherapy versus chemotherapy. Indeed, our study has several important limitations. First, SEER does not provide information on the extent of surgical resection. The inability to distinguish between gross-total, subtotal resection, and biopsy-only procedures is a major limitation, particularly in a disease where cytoreduction is tightly linked to survival 37 . Second, we lacked data on neurotoxicity, neurocognitive outcomes, and other late effects of CSI. As a result, we were unable to compare survival gains against treatment-related morbidity in a balanced way or to quantify the trade-off between oncologic control and functional outcomes in the very young. Despite these limitations, our study has notable strengths. We leveraged a large, population-based cohort and applied robust statistical methods, including propensity-score weighting and multivariable modeling, to approximate causal effects within the constraints of an observational dataset. Our models demonstrated good predictive performance and allowed for strong control of measured confounders available within SEER. In doing so, we provide contemporary, nationally representative estimates of CSI utilization and survival in infants and very young children with medulloblastoma. Future work should build on these findings through multi-institutional collaborations with granular capture of surgical, radiotherapy, and toxicity data. Such trials, particularly when integrated with molecular and immunologic profiling, will be critical to defining when CSI is necessary, when it can be safely de-escalated, and when it can be omitted altogether in infantile and very young medulloblastoma. Moreover, concise algorithms for treating molecular subtypes of pediatric medulloblastoma can unify clinical decision making across institutions and provide safer and more reliable care for such a rare but aggressive cancer. Additionally, given the disparity between clinical outcomes and the national trend in use of radiation therapy, follow up studies should further characterize and quantify risk stratification for use of radiation therapy in this specific population by identifying the disease characteristics most susceptible to radiation therapy use with minimal complications. Elucidation of these determinants will enable physicians to make informed decisions regarding radiation therapy use based on patient age, potential molecular markers, medulloblastoma subtype, other available treatment modalities and stage of tumor progression. Conclusion This investigation found that national reliance on CSI is decreasing for infant medulloblastoma. The use of CSI was correlated with survival benefits; however, the increasing use of chemotherapy and novel immunotherapies has likely decreased the prevalence of irradiation. These results highlight the ongoing tension between oncologic control and the risk of profound late effects in this vulnerable population. Future work should build on these observations through multi-institutional collaborations with detailed capture of surgical, radiotherapy, and toxicity data. Prospective studies, ideally randomized or carefully controlled, are needed to compare conventional CSI, reduced-dose or focal radiotherapy, and chemotherapy-only strategies in this cohort. Declarations Conflict of Interest Statement The authors have no conflicts of interest to declare. Funding Sources This study was not supported by any sponsor or funder. Author Contributio ns Conceptualization: S.A, S.K, Y.H, D.P; Methodology: S.A, S.K, Y.H, J.L; Software: S.A; Data Collection: S.A, S.K, J.L; Formal Analysis: S.A, S.K, A.K, A.S; Validation: S.A, Y.H, J.L, A.K, A.S, D.P, S.C; Writing (Original Draft): S.A, S.K, J.L; Writing (Review and Editing): S.A, S.K, Y.H, D.P, S.c; Supervision: Y.H, D.P, S.C Data Availability Statement No new data were generated or analyzed in this study. References Northcott PA, Jones DT, Kool M, et al. Medulloblastomics: The End of the Beginning. Nat Rev Cancer . 2012;12(12):818-834. doi:10.1038/nrc3410 Funakoshi Y, Sugihara Y, Uneda A, Nakashima T, Suzuki H. Recent advances in the molecular understanding of medulloblastoma. Cancer Science . 2023;114(3):741-749. doi:10.1111/cas.15691 Northcott PA, Buchhalter I, Morrissy AS, et al. The whole-genome landscape of medulloblastoma subtypes. Nature . 2017;547(7663):311-317. doi:10.1038/nature22973 Northcott PA, Robinson GW, Kratz CP, et al. Medulloblastoma. Nat Rev Dis Primers . 2019;5(1):1-20. doi:10.1038/s41572-019-0063-6 Prados MD. Current Strategies for Management of Medulloblastoma. Diagnostics (Basel) . 2023;13(16):2622. doi:10.3390/diagnostics13162622 Thomas A, Noël G. Medulloblastoma: optimizing care with a multidisciplinary approach. J Multidiscip Healthc . 2019;12:335-347. doi:10.2147/JMDH.S167808 Bailey S, Jacobs S, Kourti M, et al. Medulloblastoma therapy: Consensus treatment recommendations from SIOP-Europe and the European Reference Network. EJC Paediatric Oncology . 2025;5:100205. doi:10.1016/j.ejcped.2024.100205 Young S, Phaterpekar K, Tsang DS, Boldt G, Bauman GS. Proton Radiotherapy for Management of Medulloblastoma: A Systematic Review of Clinical Outcomes. Adv Radiat Oncol . 2023;8(4):101189. doi:10.1016/j.adro.2023.101189 Seidel C, Heider S, Hau P, Glasow A, Dietzsch S, Kortmann RD. Radiotherapy in Medulloblastoma—Evolution of Treatment, Current Concepts and Future Perspectives. Cancers (Basel) . 2021;13(23):5945. doi:10.3390/cancers13235945 Bishop AJ, McDonald MW, Chang AL, Esiashvili N. Infant brain tumors: incidence, survival, and the role of radiation based on Surveillance, Epidemiology, and End Results (SEER) Data. Int J Radiat Oncol Biol Phys . 2012;82(1):341-347. doi:10.1016/j.ijrobp.2010.08.020 Lafay-Cousin L, Baroni L, Ramaswamy V, Bouffet E. How do we approach the management of medulloblastoma in young children? Pediatr Blood Cancer . 2022;69(10):e29838. doi:10.1002/pbc.29838 Michalski JM, Janss AJ, Vezina LG, et al. Children’s Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy With Chemotherapy for Newly Diagnosed Average-Risk Medulloblastoma. J Clin Oncol . 2021;39(24):2685-2697. doi:10.1200/JCO.20.02730 Baroni LV, Sampor C, Gonzalez A, et al. Bridging the treatment gap in infant medulloblastoma: molecularly informed outcomes of a globally feasible regimen. Neuro Oncol . 2020;22(12):1873-1881. doi:10.1093/neuonc/noaa122 Packer RJ, Goldwein J, Nicholson HS, et al. Treatment of Children With Medulloblastomas With Reduced-Dose Craniospinal Radiation Therapy and Adjuvant Chemotherapy: A Children’s Cancer Group Study. JCO . 1999;17(7):2127-2127. doi:10.1200/JCO.1999.17.7.2127 Che WQ, Li YJ, Tsang CK, et al. How to use the Surveillance, Epidemiology, and End Results (SEER) data: research design and methodology. Military Medical Research . 2023;10(1):50. doi:10.1186/s40779-023-00488-2 Al-Wassia RK, Ghassal NM, Naga A, Awad NA, Bahadur YA, Constantinescu C. Optimization of Craniospinal Irradiation for Pediatric Medulloblastoma Using VMAT and IMRT. J Pediatr Hematol Oncol . 2015;37(7):e405-411. doi:10.1097/MPH.0000000000000418 Grill J, Sainte-Rose C, Jouvet A, et al. Treatment of medulloblastoma with postoperative chemotherapy alone: an SFOP prospective trial in young children. Lancet Oncol . 2005;6(8):573-580. doi:10.1016/S1470-2045(05)70252-7 Cohen BH, Geyer JR, Miller DC, et al. Pilot Study of Intensive Chemotherapy With Peripheral Hematopoietic Cell Support for Children Less Than 3 Years of Age With Malignant Brain Tumors, the CCG-99703 Phase I/II Study. A Report From the Children’s Oncology Group. Pediatr Neurol . 2015;53(1):31-46. doi:10.1016/j.pediatrneurol.2015.03.019 Ashley DM, Merchant TE, Strother D, et al. Induction chemotherapy and conformal radiation therapy for very young children with nonmetastatic medulloblastoma: Children’s Oncology Group study P9934. J Clin Oncol . 2012;30(26):3181-3186. doi:10.1200/JCO.2010.34.4341 Fay-McClymont TB, Ploetz DM, Mabbott D, et al. Long-term neuropsychological follow-up of young children with medulloblastoma treated with sequential high-dose chemotherapy and irradiation sparing approach. J Neurooncol . 2017;133(1):119-128. doi:10.1007/s11060-017-2409-9 Levitch CF, Malkin B, Latella L, et al. Long-term neuropsychological outcomes of survivors of young childhood brain tumors treated on the Head Start II protocol. Neurooncol Pract . 2021;8(5):609-619. doi:10.1093/nop/npab028 Neglia JP, Robison LL, Stovall M, et al. New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst . 2006;98(21):1528-1537. doi:10.1093/jnci/djj411 Landberg TG, Lindgren ML, Cavallin-Ståhl EK, et al. Improvements in the radiotherapy of medulloblastoma, 1946-1975. Cancer . 1980;45(4):670-678. doi:10.1002/1097-0142(19800215)45:43.0.co;2-k Tokars RP, Sutton HG, Griem ML. Cerebellar medulloblastoma: results of a new method of radiation treatment. Cancer . 1979;43(1):129-136. doi:10.1002/1097-0142(197901)43:13.0.co;2-y Erker C, Mynarek M, Bailey S, et al. Outcomes of Infants and Young Children With Relapsed Medulloblastoma After Initial Craniospinal Irradiation-Sparing Approaches: An International Cohort Study. J Clin Oncol . 2023;41(10):1921-1932. doi:10.1200/JCO.21.02968 Kiltie AE, Lashford LS, Gattamaneni HR. Survival and late effects in medulloblastoma patients treated with craniospinal irradiation under three years old. Med Pediatr Oncol . 1997;28(5):348-354. doi:10.1002/(sici)1096-911x(199705)28:53.0.co;2-h Salceda-Rivera V, Tejocote-Romero I, Osorio DS, et al. Impact of treatment and clinical characteristics on the survival of children with medulloblastoma in Mexico. Front Oncol . 2024;14:1376574. doi:10.3389/fonc.2024.1376574 Mulhern RK, Merchant TE, Gajjar A, Reddick WE, Kun LE. Late neurocognitive sequelae in survivors of brain tumours in childhood. Lancet Oncol . 2004;5(7):399-408. doi:10.1016/S1470-2045(04)01507-4 Lafay-Cousin L, Bouffet E, Hawkins C, Amid A, Huang A, Mabbott DJ. Impact of radiation avoidance on survival and neurocognitive outcome in infant medulloblastoma. Curr Oncol . 2009;16(6):21-28. doi:10.3747/co.v16i6.435 Remke M, Ramaswamy V. Infant medulloblastoma - learning new lessons from old strata. Nat Rev Clin Oncol . 2018;15(11):659-660. doi:10.1038/s41571-018-0071-6 Robinson GW, Gajjar A. Genomics Paves the Way for Better Infant Medulloblastoma Therapy. J Clin Oncol . 2020;38(18):2010-2013. doi:10.1200/JCO.20.00593 Kramer K, Pandit-Taskar N, Humm JL, et al. A phase II study of radioimmunotherapy with intraventricular 131 I-3F8 for medulloblastoma. Pediatr Blood Cancer . 2018;65(1). doi:10.1002/pbc.26754 Kabir TF, Kunos CA, Villano JL, Chauhan A. Immunotherapy for Medulloblastoma: Current Perspectives. Immunotargets Ther . 2020;9:57-77. doi:10.2147/ITT.S198162 Voskamp MJ, Li S, van Daalen KR, Crnko S, Ten Broeke T, Bovenschen N. Immunotherapy in Medulloblastoma: Current State of Research, Challenges, and Future Perspectives. Cancers (Basel) . 2021;13(21):5387. doi:10.3390/cancers13215387 Rusert JM, Juarez EF, Brabetz S, et al. Functional Precision Medicine Identifies New Therapeutic Candidates for Medulloblastoma. Cancer Res . 2020;80(23):5393-5407. doi:10.1158/0008-5472.CAN-20-1655 Rutkowski S, Gerber NU, von Hoff K, et al. Treatment of early childhood medulloblastoma by postoperative chemotherapy and deferred radiotherapy. Neuro Oncol . 2009;11(2):201-210. doi:10.1215/15228517-2008-084 Zeltzer PM, Boyett JM, Finlay JL, et al. Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: conclusions from the Children’s Cancer Group 921 randomized phase III study. J Clin Oncol . 1999;17(3):832-845. doi:10.1200/JCO.1999.17.3.832 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 04 May, 2026 Reviewers invited by journal 04 May, 2026 Editor assigned by journal 10 Apr, 2026 Submission checks completed at journal 10 Apr, 2026 First submitted to journal 08 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9361013","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":634146380,"identity":"9025867e-54b5-4f7a-a8e8-4c775c1ef46b","order_by":0,"name":"Shreyas Annagiri","email":"","orcid":"","institution":"Stanford University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Shreyas","middleName":"","lastName":"Annagiri","suffix":""},{"id":634146382,"identity":"600b4ac3-095d-4d61-aa35-b07583dd5460","order_by":1,"name":"Samuel Kim","email":"","orcid":"","institution":"University of Missouri-Kansas City School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Samuel","middleName":"","lastName":"Kim","suffix":""},{"id":634146384,"identity":"b6a7bec9-53c5-4443-9407-57f3c47b46f5","order_by":2,"name":"Yusuke S. Hori","email":"","orcid":"","institution":"Stanford University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yusuke","middleName":"S.","lastName":"Hori","suffix":""},{"id":634146385,"identity":"33aceaa3-d7b7-4317-ab12-510e06a676a2","order_by":3,"name":"Justin Liu","email":"","orcid":"","institution":"Stanford University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Justin","middleName":"","lastName":"Liu","suffix":""},{"id":634146389,"identity":"5ccb1320-59fe-4a31-ae99-542aa72026cb","order_by":4,"name":"Ahed Kattaa","email":"","orcid":"","institution":"Stanford University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Ahed","middleName":"","lastName":"Kattaa","suffix":""},{"id":634146391,"identity":"50dbd382-bc74-4793-82a5-78489b808d1d","order_by":5,"name":"Amirhossein Sigari","email":"","orcid":"","institution":"Stanford University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Amirhossein","middleName":"","lastName":"Sigari","suffix":""},{"id":634146395,"identity":"6afd4db8-2d4c-4715-8543-4fbb003326f6","order_by":6,"name":"David Park","email":"","orcid":"","institution":"Stanford University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"David","middleName":"","lastName":"Park","suffix":""},{"id":634146397,"identity":"eab8d177-9f68-4f17-8c5c-ff06c6ded9c4","order_by":7,"name":"Steven Chang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6ElEQVRIiWNgGAWjYFCCBDYQKQdmVzAwMDYwMBgQpcWYAUSdIUVLYgPRWuTbk589+LmjNn3+/OZnDw5U3JNtYG/eJoFPi8GZZ+aGvWeO5244xmZucOBMsXEDz7Ey/FokctgkeNuO5W5gYzCT/tiWkNggkWOGV4v8jBw2yb9tx9Ll29i/SRwEaZF/g18Lw40cNmnetpoEhmM8ZhAtEjz4tQD9YiYt23bAcMOxnDKJA2cSjNt40oot8DoMGGKSb9vq5OWbj2+TOFCRINvPfnjjDbwOg4DDCCYbEcpBoI5IdaNgFIyCUTAiAQBDCkwgDHfjJQAAAABJRU5ErkJggg==","orcid":"","institution":"Stanford University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Steven","middleName":"","lastName":"Chang","suffix":""}],"badges":[],"createdAt":"2026-04-08 20:53:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9361013/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9361013/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109205863,"identity":"3298abf2-6c0c-4b46-88fc-2a29725707e8","added_by":"auto","created_at":"2026-05-13 15:08:54","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1305924,"visible":true,"origin":"","legend":"\u003cp\u003eProportion of surgically resected medulloblastoma cases receiving postoperative external‑beam radiation for each calendar year from 2000 to 2021; points denote yearly values and the connecting line illustrates the temporal trend relative to the total number of surgically treated cases in that year.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-9361013/v1/970b1147ddb22ec2e896f564.png"},{"id":109205846,"identity":"c0789020-84a9-4f7d-ad7e-ee6989e0dea3","added_by":"auto","created_at":"2026-05-13 15:08:34","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1461348,"visible":true,"origin":"","legend":"\u003cp\u003eLove plot demonstrating standard mean differences for all covariates in the propensity score model. SMDs prior to weighting are shown in red, while SMDs following inverse probability of treatment weighting are shown in blue. Vertical dashed lines denote the relevant threshold of ± 0.1 demonstrating adequate balance.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-9361013/v1/a220ca1fd8f2a4a248536535.png"},{"id":109205875,"identity":"89cf6913-6d14-43cb-8489-6ffc132f1d22","added_by":"auto","created_at":"2026-05-13 15:09:01","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":972528,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier estimates of overall survival for surgically resected medulloblastoma for patients who received radiation therapy versus did not; tick marks indicate censored observations, numbers at risk are displayed beneath the plot, and the reported p‑value is derived from a two‑sided log‑rank test comparing the survival curves.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-9361013/v1/d96254e1d0ee2e4a2ac597cf.png"},{"id":109205843,"identity":"7bd09048-e505-4e92-af5a-0fef7c0f928b","added_by":"auto","created_at":"2026-05-13 15:08:34","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1002643,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier estimates of cancer specific survival for surgically resected medulloblastoma for patients who received radiation therapy versus did not; tick marks indicate censored observations, numbers at risk are displayed beneath the plot, and the reported p‑value is derived from a two‑sided log‑rank test comparing the survival curves.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-9361013/v1/720e736867180af129a53b60.png"},{"id":109207206,"identity":"b306f976-8bb0-4bc9-8979-513bf527e315","added_by":"auto","created_at":"2026-05-13 15:18:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5038760,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9361013/v1/5440e675-2f34-45de-886d-1570fce071c7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Efficacy and Determinants of Adjuvant Radiation Therapy for Medulloblastoma Patients under 4: A Propensity Score Matched National Cohort Study of Survival Outcomes","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMedulloblastomas (MB) are the most common primary central nervous system malignancy in children (WHO Grade IV), composed of neuroepithelial cells most commonly seeding in the cerebellar vermis, hemisphere or the fourth ventricle of the brain. MBs are clinically heterogenous, classified by both histology and canonical molecular markers with well-defined differences in prognosis and incidence in children. The subtypes of MB include WNT activated MB, SHH activated MB, Group 3 MB, and Group 4 MB\u003csup\u003e1,2,3\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eMBs are routinely treated with a combination of maximum obtainable surgical resection, chemotherapy and cerebrospinal irradiation (CSI)\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. While treatment plans differ depending on indicated tumor progression, as well as known histological and molecular classifications, randomized control trials involving patients with MB have consistently demonstrated a survival benefit from adjuvant or post-surgical CSI.\u003c/p\u003e \u003cp\u003eHowever, the role of adjuvant CSI as a mainstay treatment for infants and pediatric patients under the age of 3 remains opaque\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Although CSI may be efficacious in eliminating residual tumor growth and recurrence, potential neurotoxic and neurodevelopmental complications of radiation treatment may be exacerbated in younger patient populations\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Consequently, in the past decade, select institutions have opted to treat medulloblastoma cases in patients under the age of 3\u0026ndash;4 with surgical resection and chemotherapy, avoiding CSI as a primary treatment modality and restricting its use to cases with extensive tumor proliferation or diffusion\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Additionally, recent stage III clinical trials have demonstrated the potential of reduced dose CSI as an alternative to traditional treatment regimens in young patients\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Of note, however, reduced dose CSI demonstrated worse survival in young medulloblastoma patients despite improved neurocognitive outcomes.\u003c/p\u003e \u003cp\u003eGiven the heterogeneity of results in the literature as demonstrated from single and multi-institutional studies, it has become increasingly necessary to determine the universality of the shift in the use of radiation therapy for medulloblastoma cases under the age of four and resultant differences in outcomes at the national level\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. The Surveillance, Epidemiology and End Results (SEER) program from the National Cancer Institute is one of the most substantiative population-based tumor registries in the United States that enables the monitoring of cancer incidence and nationwide trends in cancer treatment\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. The recent 2025 update to the SEERs registry ensures improved data quality and increased granularity of individual patient clinical details and treatment outcomes. To elucidate national patterns in radiation treatment for medulloblastoma cases under the age of 4, we conducted a retrospective analysis of the newly updated SEERs registry from 2000 to 2021.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe Surveillance, Epidemiology and End Results (SEERS) 17 database, a dataset of oncology cases diagnosed from 2000 to 2021 with time-dependent and county level indicators of socioeconomic status such as income and urbanization status, was utilized for analysis. The SEERS-17 database is sponsored by the National Cancer Institute and involves the collection of clinical and public health data from 17 different registries to monitor the incidence of cancer in various regions of the United States. The SEERS-17 database covers roughly 26% of the United States population and thus provides a large national sample size of clinical characteristics and outcomes in tumor patients.\u003c/p\u003e \u003cp\u003eThrough the SEERs*Stat software, the SEERS-17 database was queried for all cases with medulloblastoma (ICD 9470/3), receipt of chemotherapy, receipt of surgery, and age from 0 to 4 years. Cases which reported radiation treatment as \u0026lsquo;recommended, unknown if administered\u0026rsquo;, and \u0026lsquo;combination of beam with implants or isotopes\u0026rsquo; were excluded from analysis. Cases where radiation treatment was given prior to surgical resection or where the sequence of surgery and radiation was unknown were excluded. Cases where radiation treatment was given intraoperatively or radiation treatment was given both before and after surgery were excluded to limit the radiation cohort to patients who received adjuvant radiation therapy. Extracted clinical characteristics included year of diagnosis, histology, primary site, cause of death, survival months, radiation treatment receipt, race/ethnicity, age group, and income status.\u003c/p\u003e \u003cp\u003eThis analysis utilized aggregation of certain clinical variables to account for low sample size attributed to the rarity of the tumor of interest. Race levels were aggregated to \u0026ldquo;Hispanic (All Races)\u0026rdquo;, \u0026ldquo;Non-Hispanic White\u0026rdquo; and \u0026ldquo;Non-Hispanic Minority\u0026rdquo; (composed of Asian/Pacific Islander, Black, Native American/Alaskan Native, and Unknown races). Annual income levels were aggregated for this analysis into levels \u0026lt;\u003cspan\u003e$\u003c/span\u003e40k-\u003cspan\u003e$\u003c/span\u003e59,999 USD, \u003cspan\u003e$\u003c/span\u003e60k - \u003cspan\u003e$\u003c/span\u003e89,999 USD, \u003cspan\u003e$\u003c/span\u003e90k - \u003cspan\u003e$\u003c/span\u003e119,999 USD, and \u0026gt;\u003cspan\u003e$\u003c/span\u003e120k USD. Occipital and \u0026ldquo;overlapping region of the brain\u0026rdquo; primary sites were aggregated into the category \u0026ldquo;other\u0026rdquo; due to the low number of patients with tumors stemming from either site. The resulting aggregated levels for primary site included \u0026ldquo;Cerebellum\u0026rdquo;, \u0026ldquo;Brainstem\u0026rdquo;, \u0026ldquo;Brain, Unspecified\u0026rdquo;, \u0026ldquo;Ventricle\u0026rdquo; and \u0026ldquo;Other\u0026rdquo;. The histology variable contained levels of \u0026ldquo;Medulloblastoma, Unspecified\u0026rdquo;, \u0026ldquo;Large cell Medulloblastoma\u0026rdquo;, \u0026ldquo;WNT Activated Medulloblastoma\u0026rdquo;, \u0026ldquo;SHH activated Medulloblastoma\u0026rdquo;, and \u0026ldquo;Medulloblastoma, group 4\u0026rdquo;. Variable reference levels were standardized for all analyses. For radiation, the reference level indicated patients who received radiation treatment. For sex, the reference level indicated \u0026ldquo;Female\u0026rdquo;. For race, the reference level indicated \u0026ldquo;Non-Hispanic White\u0026rdquo;. For annual income, the reference level indicated the lowest class, or \u0026lt;\u003cspan\u003e$\u003c/span\u003e40k-\u003cspan\u003e$\u003c/span\u003e59,999 USD. For primary site, the reference level indicated \u0026ldquo;Ventricle\u0026rdquo;.\u003c/p\u003e \u003cp\u003eThe trend in proportion of cases over time for which radiation therapy was utilized was computed. A Chi-Square test for independence to determine differences in population demographics between radiation and no radiation cohort was conducted. 1:1 Propensity score matching (PSM) with a caliper of 0.03 was utilized to account for confounding variables, creating a matched cohort for causal analysis. Kaplan Meier (KM) curves were computed for matched patients assessing both overall survival (OS) and cancer specific survival (CSS). Univariate cox survival analysis for the matched patients was conducted to determine the impact of radiation receipt on OS and CSS. Finally, a multivariate binomial regression model with fixed effects of age, year of diagnosis, race, histology, primary site, and income was used to assess determinants of radiation receipt. All statistical analyses were conducted using the programming language R (version 4.4.0; R Foundation for Statistical Computing, Vienna, Austria) within the RStudio\u0026reg; environment (Posit Software, Boston, MA, USA), using a significance threshold of p\u0026thinsp;=\u0026thinsp;0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eCohort Characteristics\u003c/h2\u003e \u003cp\u003ePrior to propensity score matching, 427 patients under the age of 4 with surgically resected medulloblastomas were identified for analysis. 53.1% of patients underwent beam radiation (n\u0026thinsp;=\u0026thinsp;227), while 46.9% of patients had none or unknown radiation (n\u0026thinsp;=\u0026thinsp;220).\u003c/p\u003e \u003cp\u003eIn the cohort of patients who underwent radiation, 54.6% were non-Hispanic white (n\u0026thinsp;=\u0026thinsp;124), 29.5% were Hispanic (n\u0026thinsp;=\u0026thinsp;67), and 15.9% were non-Hispanic minority (n\u0026thinsp;=\u0026thinsp;36). 32.6% of this cohort was female (n\u0026thinsp;=\u0026thinsp;74), while 67.4% (n\u0026thinsp;=\u0026thinsp;153) was male. 3.1% (n\u0026thinsp;=\u0026thinsp;7) of patients in this cohort were under 1 year of age, while 96.9%(n\u0026thinsp;=\u0026thinsp;220) were between the age of 1 and 4 years. 87.2% (n\u0026thinsp;=\u0026thinsp;198) of patients who underwent radiation were diagnosed with classical or unspecified medulloblastoma, 8.4% (n\u0026thinsp;=\u0026thinsp;19) were diagnosed with large cell medulloblastoma, and 3.4% (n\u0026thinsp;=\u0026thinsp;8) were diagnosed with group 4 medulloblastoma. This cohort additionally contained one patient who was diagnosed with WNT-activated medulloblastoma, and one patient who was diagnosed with SHH-activated medulloblastoma.\u003c/p\u003e \u003cp\u003eIn the cohort of patients who did not undergo radiation, 36.4% (n\u0026thinsp;=\u0026thinsp;80) of patients were Hispanic, 48.6% (n\u0026thinsp;=\u0026thinsp;107) were non-Hispanic White, and 15% (n\u0026thinsp;=\u0026thinsp;33) were non-Hispanic minority. 34.5% (n\u0026thinsp;=\u0026thinsp;76) of this cohort was female while 65.5% (n\u0026thinsp;=\u0026thinsp;144) were male. 13.2% (n\u0026thinsp;=\u0026thinsp;29) of these patients were under the age of 1 year, while 86.8% (n\u0026thinsp;=\u0026thinsp;191) were between the ages of 1 and 4 years. 81.8% (n\u0026thinsp;=\u0026thinsp;180) were diagnosed with classical or unspecific medulloblastoma, 7.3% (n\u0026thinsp;=\u0026thinsp;16) were diagnosed with large cell medulloblastoma, and 10% (n\u0026thinsp;=\u0026thinsp;22) were diagnosed with group 4 medulloblastoma. The non-radiation cohort contained one patient diagnosed with WNT-activated medulloblastoma and one patient diagnosed with SHH-activated medulloblastoma.\u003c/p\u003e \u003cp\u003eThe distribution of ages was statistically different between the radiation and no radiation cohort (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{\\chi\\:}^{2}\\)\u003c/span\u003e\u003c/span\u003e, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), while all other collected demographic variables demonstrated no significant difference between the two cohorts. [Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient Demographics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRadiation (n\u0026thinsp;=\u0026thinsp;227)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo/Unknown Radiation (n\u0026thinsp;=\u0026thinsp;220)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{\\varvec{\\chi\\:}}^{2}\\:\\)\u003c/span\u003e\u003c/span\u003eP-Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge category (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;1 year\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (3.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (13.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e1\u0026ndash;4 years\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e220 (96.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e191 (86.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.737\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFemale\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74 (32.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76 (34.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMale\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e153 (67.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e144 (65.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRace (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.298\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHispanic (All Races)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67 (29.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80 (36.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNon-Hispanic White\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e124 (54.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e107 (48.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNon-Hispanic Minority\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (15.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33 (15.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistology (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.110\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUnspecified/Classical\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e198 (87.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e180 (81.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLarge Cell\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (8.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (7.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGroup 4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (3.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (10.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWNT Activated\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSHH Activated\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnnual Income (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.332\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e120k+\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (4.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (6.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e90k-119k\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76 (33.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62 (28.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e60k-89k\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e121 (53.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e116 (52.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;40k \u0026ndash; 59k\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (8.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (12.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eP values were reported from a X\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e \u003cb\u003etest for independence conducted for each variable.\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eTrend in Radiation Receipt\u003c/h3\u003e\n\u003cp\u003eThe trend in the proportion of surgically resected medulloblastoma cases under 4 years of age for which adjuvant radiation therapy was given demonstrated a decrease with time (r=-0.759) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003ePropensity Score Matching\u003c/h3\u003e\n\u003cp\u003ePropensity Score matching across sex, primary site, race, income and histology resulted in a matched cohort of 142 patients. Plotting of standard mean differences (SMD) between patients of each treatment group prior to and following PSM demonstrated a well-balanced cohort, with SMDs between matched patients falling below a value of 0.1 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003ePSM OS and CSS\u003c/h3\u003e\n\u003cp\u003eKaplan Meier analysis for overall survival (OS) in the PSM cohort demonstrated a median OS of 267 days for patients who received radiation and 242 days for patients who did not receive radiation. Differences in survival approached significance (p\u0026thinsp;=\u0026thinsp;0.056, log rank test) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Kaplan Meier analysis for cancer specific survival (CSS) in the PSM demonstrated trends of improved survival with no significant difference observed (p\u0026thinsp;=\u0026thinsp;0.098, log rank test) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePSM Cox Regression for Overall Survival\u003c/h2\u003e \u003cp\u003eA univariate propensity score weighted cox regression for differences in overall survival determined by radiation receipt demonstrated significantly improved OS for patients who received radiation therapy (HR\u0026thinsp;=\u0026thinsp;0.56, 95% CI 0.41\u0026ndash;0.78, p\u0026thinsp;=\u0026thinsp;0.0004). The cox regression model demonstrated moderate discrimination between survivors and non-survivors (concordance\u0026thinsp;=\u0026thinsp;0.64) [Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e]. The determined effect was supported by the Wald test (p\u0026thinsp;=\u0026thinsp;0.0004), likelihood ratio test (p\u0026thinsp;=\u0026thinsp;0.009), and robust score test (p\u0026thinsp;=\u0026thinsp;0.0002).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEffect of Radiotherapy on Overall and Cancer-Specific Survival in Medulloblastoma (Propensity Score\u0026ndash;Weighted Cox Analysis) \u003cb\u003eFootnote\u003c/b\u003e: Hazard ratios were estimated using propensity score\u0026ndash;weighted Cox proportional hazards models, stratified by matching subclass and using robust standard errors. Concordance indicates Harrell\u0026rsquo;s C index.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEvents\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eComparison\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP-Value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eConcordance\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOverall Survival\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e284\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e106\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRadiation vs No Radiation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.56 (0.41\u0026ndash;0.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCancer-Specific Survival\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e284\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRadiation vs No Radiation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.57 (0.40\u0026ndash;0.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePSM Cox Regression for Cancer Specific Survival\u003c/h3\u003e\n\u003cp\u003eA univariate propensity score weighted cox regression for differences in cancer specific survival determined by radiation receipt demonstrated significantly improved CSS for patients who received radiation therapy (HR\u0026thinsp;=\u0026thinsp;0.57, 95% CI 0.40\u0026ndash;0.80, p\u0026thinsp;=\u0026thinsp;0.001). The cox regression model for CSS demonstrated equally competent discriminative ability between survivors and non-survivors as the OS model (concordance\u0026thinsp;=\u0026thinsp;0.64) [Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e]. The determined effect on CSS was further supported by the Wald test (p\u0026thinsp;=\u0026thinsp;0.001), robust score test (p\u0026thinsp;=\u0026thinsp;0.0007), and likelihood ratio test (p\u0026thinsp;=\u0026thinsp;0.02).\u003c/p\u003e\n\u003ch3\u003eDeterminants of Radiation Treatment\u003c/h3\u003e\n\u003cp\u003eThrough multivariate binomial logistic regression analysis, significant clinical characteristics associated with radiation treatment compared to no radiation treatment were assessed. Older age(β\u0026thinsp;=\u0026thinsp;1.36, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and earlier year of diagnosis (β = \u0026minus;\u0026thinsp;0.08, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were associated with increased radiation receipt. Inclusion of covariates significantly improved model fit (Δ Deviance\u0026thinsp;=\u0026thinsp;52.3, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; AIC\u0026thinsp;=\u0026thinsp;601.3) [Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBinomial logistic regression analysis of factors associated with receipt of adjuvant radiation therapy in MB\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOdds Ratio\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI (OR)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eYear of Diagnosis\u003c/b\u003e \u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.923\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.891\u0026ndash;0.956\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e \u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.912\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.163\u0026ndash;7.738\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFemale\u003c/b\u003e ᵃ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMale\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.113\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.729\u0026ndash;1.699\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.619\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRace\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWhite\u003c/b\u003e ᵃ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHispanic (All Races)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.757\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.479\u0026ndash;1.193\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.232\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNon-Hispanic Minority\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.081\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.603\u0026ndash;1.946\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.794\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIncome\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e40k-59,999\u003c/b\u003e ᵃ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e60k \u0026ndash; 89,999\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.393\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.715\u0026ndash;2.750\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003csup\u003e0.332\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e90k \u0026ndash; 119,999\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.669\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.824\u0026ndash;3.420\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003csup\u003e0.157\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e120k+\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.311\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.441\u0026ndash;3.844\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.621\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedulloblastoma Type\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClassical (NOS)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLarge cell\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.547\u0026ndash;2.449\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.712\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGroup 4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.596\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.223\u0026ndash;1.470\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.277\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWNT-Activated\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.876\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.071\u0026ndash;49.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.665\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSHH-Activated\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.875\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.070\u0026ndash;49.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.664\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePrimary Site\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVentricle\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCerebellum\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.513\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.164\u0026ndash;1.499\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.230\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBrain Stem\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.579\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.169\u0026ndash;1.876\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.369\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBrain, NOS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.492\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.124\u0026ndash;1.852\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.299\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOther\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.493\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.036\u0026ndash;12.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.603\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003ea\u003c/sup\u003e Reference category, \u003csup\u003eb\u003c/sup\u003e p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, \u003csup\u003ec\u003c/sup\u003e p\u0026thinsp;\u0026lt;\u0026thinsp;0.01, \u003csup\u003ed\u003c/sup\u003e p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Odds ratios and 95% confidence intervals are reported for each covariate, the outcome variable was receipt of adjuvant radiation therapy (yes vs. no).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eᵃ\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eNational trends for CSI in children under 4 years of age for medulloblastoma have decreased year-by-year (r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.759, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). This is likely attributable to the continued controversy surrounding the use of CSI in infants and young children because of its acute and long-term toxicities\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. Our study suggests that the therapeutic sequelae has largely discouraged the use of CSI in pediatric medulloblastoma. Indeed, age correlated positively with irradiation patterns on multivariable analysis (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), suggesting that toxicity, particularly in infants, dissuades clinicians from utilizing CSI to treat pediatric medulloblastoma in the very young. This is consistent with current advancements in clinical trials for the very young and the appropriate avoidance of late neurocognitive effects\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Temporal trends for increasingly lower rates of CSI for pediatric medulloblastoma were also confirmed on multivariable analysis.\u003c/p\u003e \u003cp\u003eStill, CSI improved CSS and OS in our propensity-score weighted models. While Kaplan Meier models demonstrated only marginal effects, CSI was associated with an approximately 43% decrease in relative risk for overall survival and cancer specific mortality in our cohort as modelled by cox proportional hazards. Additionally, previous clinical trials have demonstrated survival benefits from standard dose CSI as opposed to lose dose CSI\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThese survival outcomes suggest the CSI remains largely therapeutic, although the year-by-year variability of the very young tends to create discourse in the use of CSI for medulloblastoma. This follows evidence for the efficacy of CSI in whole-group analysis\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOverall, frontline and salvage CSI is a considerable therapy for infant and young childhood medulloblastoma\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. Although our study did not consider frontline versus salvage irradiation, our study found that CSI improved survival in line with the recent literature\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e,\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. National trends suggest that the use of CSI continues to be controversial due to the profound late effects including neurocognitive and development delay\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e,\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. These decisions seemingly exist despite evidence to support survival penalties in delayed or excluded CSI therapy in the very young\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. Recent efforts to stratify pediatric medulloblastoma by molecular traits have helped reduce radiotherapy while maintaining survival benefits through chemotherapy alone\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. Our study suggests that molecular subtyping and the preference for reduced radiotherapy convention is increasing, with more evidence for effective management utilizing genomic data in infant and very young pathology\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. Our group did not subcategorize for the molecular markers of pediatric medulloblastoma in order to protect the power of the statistical analyses. However, radiotherapy and chemotherapy trends likely differ between histological and molecular subtypes, and future research should explore trends in clinical decision-making across molecular subtypes.\u003c/p\u003e \u003cp\u003eImmunotherapy for pediatric and adult medulloblastoma has likely changed the landscape of clinical practice, as well. Immunotherapy for infantile medulloblastoma opens the door for improved survival while mitigating the drastic effects of chemoradiotherapy. A recent Phase II study has found benefits for primary and relapse medulloblastoma utilizing combined monoclonal antibodies and radiotherapy\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e. Other studies have demonstrated the possible efficacy of oncolytic viruses for increasing cell recognition of medulloblastoma antigens\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e. Clinical trials are currently underway exploring the use of viruses for the therapy of medulloblastoma with hopes of immune reactivity unlike more T-cell exhausted tumors like glioblastoma. However, current evidence from vaccine therapy demonstrates considerable immunosuppressive behavior in medulloblastoma\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e, with special considerations in infantile medulloblastoma and the naive immune system. Even so, continued work to identify molecular and genetic signatures in medulloblastoma and to understand the tumor immune microenvironment has unlocked new possibilities regarding therapeutic strategies and precision medicine\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eUltimately, the use of CSI will continue to decrease in the treatment of infantile and very young medulloblastoma with a greater emphasis on chemotherapy alone recommendations\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e. Rescue CSI may always be necessary for particular subtypes or behaviors of medulloblastoma, and consistent survival benefits are noted for OS and CSS in this study. However, our study did not differentiate between molecular subtypes and, furthermore, did not evaluate for radiotherapy versus chemotherapy. Indeed, our study has several important limitations. First, SEER does not provide information on the extent of surgical resection. The inability to distinguish between gross-total, subtotal resection, and biopsy-only procedures is a major limitation, particularly in a disease where cytoreduction is tightly linked to survival\u003csup\u003e\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e. Second, we lacked data on neurotoxicity, neurocognitive outcomes, and other late effects of CSI. As a result, we were unable to compare survival gains against treatment-related morbidity in a balanced way or to quantify the trade-off between oncologic control and functional outcomes in the very young. Despite these limitations, our study has notable strengths. We leveraged a large, population-based cohort and applied robust statistical methods, including propensity-score weighting and multivariable modeling, to approximate causal effects within the constraints of an observational dataset. Our models demonstrated good predictive performance and allowed for strong control of measured confounders available within SEER. In doing so, we provide contemporary, nationally representative estimates of CSI utilization and survival in infants and very young children with medulloblastoma.\u003c/p\u003e \u003cp\u003eFuture work should build on these findings through multi-institutional collaborations with granular capture of surgical, radiotherapy, and toxicity data. Such trials, particularly when integrated with molecular and immunologic profiling, will be critical to defining when CSI is necessary, when it can be safely de-escalated, and when it can be omitted altogether in infantile and very young medulloblastoma. Moreover, concise algorithms for treating molecular subtypes of pediatric medulloblastoma can unify clinical decision making across institutions and provide safer and more reliable care for such a rare but aggressive cancer. Additionally, given the disparity between clinical outcomes and the national trend in use of radiation therapy, follow up studies should further characterize and quantify risk stratification for use of radiation therapy in this specific population by identifying the disease characteristics most susceptible to radiation therapy use with minimal complications. Elucidation of these determinants will enable physicians to make informed decisions regarding radiation therapy use based on patient age, potential molecular markers, medulloblastoma subtype, other available treatment modalities and stage of tumor progression.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis investigation found that national reliance on CSI is decreasing for infant medulloblastoma. The use of CSI was correlated with survival benefits; however, the increasing use of chemotherapy and novel immunotherapies has likely decreased the prevalence of irradiation. These results highlight the ongoing tension between oncologic control and the risk of profound late effects in this vulnerable population. Future work should build on these observations through multi-institutional collaborations with detailed capture of surgical, radiotherapy, and toxicity data. Prospective studies, ideally randomized or carefully controlled, are needed to compare conventional CSI, reduced-dose or focal radiotherapy, and chemotherapy-only strategies in this cohort.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cu\u003eConflict of Interest Statement\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest to declare.\u003c/p\u003e\n\u003ch6 id=\"_Toc472330566\"\u003e\u003cu\u003eFunding Sources\u003c/u\u003e\u003c/h6\u003e\n\u003cp id=\"_Toc472330568\"\u003eThis study was not supported by any sponsor or funder.\u003c/p\u003e\n\u003ch6\u003e\u003cu\u003eAuthor Contributio\u003c/u\u003e\u003cu\u003ens\u0026nbsp;\u003c/u\u003e\u003c/h6\u003e\n\u003ch6\u003eConceptualization: S.A, S.K, Y.H, D.P; Methodology: S.A, S.K, Y.H, J.L; Software: S.A; Data Collection: S.A, S.K, J.L; Formal Analysis: S.A, S.K, A.K, A.S; Validation: S.A, Y.H, J.L, A.K, A.S, D.P, S.C; Writing (Original Draft): S.A, S.K, J.L; Writing (Review and Editing): S.A, S.K, Y.H, D.P, S.c; Supervision: Y.H, D.P, S.C\u003c/h6\u003e\n\u003cp\u003e\u003cu\u003eData Availability Statement\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eNo new data were generated or analyzed in this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eNorthcott PA, Jones DT, Kool M, et al. Medulloblastomics: The End of the Beginning. \u003cem\u003eNat Rev Cancer\u003c/em\u003e. 2012;12(12):818-834. doi:10.1038/nrc3410\u003c/li\u003e\n \u003cli\u003eFunakoshi Y, Sugihara Y, Uneda A, Nakashima T, Suzuki H. Recent advances in the molecular understanding of medulloblastoma. \u003cem\u003eCancer Science\u003c/em\u003e. 2023;114(3):741-749. doi:10.1111/cas.15691\u003c/li\u003e\n \u003cli\u003eNorthcott PA, Buchhalter I, Morrissy AS, et al. The whole-genome landscape of medulloblastoma subtypes. \u003cem\u003eNature\u003c/em\u003e. 2017;547(7663):311-317. doi:10.1038/nature22973\u003c/li\u003e\n \u003cli\u003eNorthcott PA, Robinson GW, Kratz CP, et al. Medulloblastoma. \u003cem\u003eNat Rev Dis Primers\u003c/em\u003e. 2019;5(1):1-20. doi:10.1038/s41572-019-0063-6\u003c/li\u003e\n \u003cli\u003ePrados MD. Current Strategies for Management of Medulloblastoma. \u003cem\u003eDiagnostics (Basel)\u003c/em\u003e. 2023;13(16):2622. doi:10.3390/diagnostics13162622\u003c/li\u003e\n \u003cli\u003eThomas A, No\u0026euml;l G. Medulloblastoma: optimizing care with a multidisciplinary approach. \u003cem\u003eJ Multidiscip Healthc\u003c/em\u003e. 2019;12:335-347. doi:10.2147/JMDH.S167808\u003c/li\u003e\n \u003cli\u003eBailey S, Jacobs S, Kourti M, et al. Medulloblastoma therapy: Consensus treatment recommendations from SIOP-Europe and the European Reference Network. \u003cem\u003eEJC Paediatric Oncology\u003c/em\u003e. 2025;5:100205. doi:10.1016/j.ejcped.2024.100205\u003c/li\u003e\n \u003cli\u003eYoung S, Phaterpekar K, Tsang DS, Boldt G, Bauman GS. Proton Radiotherapy for Management of Medulloblastoma: A Systematic Review of Clinical Outcomes. \u003cem\u003eAdv Radiat Oncol\u003c/em\u003e. 2023;8(4):101189. doi:10.1016/j.adro.2023.101189\u003c/li\u003e\n \u003cli\u003eSeidel C, Heider S, Hau P, Glasow A, Dietzsch S, Kortmann RD. Radiotherapy in Medulloblastoma\u0026mdash;Evolution of Treatment, Current Concepts and Future Perspectives. \u003cem\u003eCancers (Basel)\u003c/em\u003e. 2021;13(23):5945. doi:10.3390/cancers13235945\u003c/li\u003e\n \u003cli\u003eBishop AJ, McDonald MW, Chang AL, Esiashvili N. Infant brain tumors: incidence, survival, and the role of radiation based on Surveillance, Epidemiology, and End Results (SEER) Data. \u003cem\u003eInt J Radiat Oncol Biol Phys\u003c/em\u003e. 2012;82(1):341-347. doi:10.1016/j.ijrobp.2010.08.020\u003c/li\u003e\n \u003cli\u003eLafay-Cousin L, Baroni L, Ramaswamy V, Bouffet E. How do we approach the management of medulloblastoma in young children? \u003cem\u003ePediatr Blood Cancer\u003c/em\u003e. 2022;69(10):e29838. doi:10.1002/pbc.29838\u003c/li\u003e\n \u003cli\u003eMichalski JM, Janss AJ, Vezina LG, et al. Children\u0026rsquo;s Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy With Chemotherapy for Newly Diagnosed Average-Risk Medulloblastoma. \u003cem\u003eJ Clin Oncol\u003c/em\u003e. 2021;39(24):2685-2697. doi:10.1200/JCO.20.02730\u003c/li\u003e\n \u003cli\u003eBaroni LV, Sampor C, Gonzalez A, et al. Bridging the treatment gap in infant medulloblastoma: molecularly informed outcomes of a globally feasible regimen. \u003cem\u003eNeuro Oncol\u003c/em\u003e. 2020;22(12):1873-1881. doi:10.1093/neuonc/noaa122\u003c/li\u003e\n \u003cli\u003ePacker RJ, Goldwein J, Nicholson HS, et al. Treatment of Children With Medulloblastomas With Reduced-Dose Craniospinal Radiation Therapy and Adjuvant Chemotherapy: A Children\u0026rsquo;s Cancer Group Study. \u003cem\u003eJCO\u003c/em\u003e. 1999;17(7):2127-2127. doi:10.1200/JCO.1999.17.7.2127\u003c/li\u003e\n \u003cli\u003eChe WQ, Li YJ, Tsang CK, et al. How to use the Surveillance, Epidemiology, and End Results (SEER) data: research design and methodology. \u003cem\u003eMilitary Medical Research\u003c/em\u003e. 2023;10(1):50. doi:10.1186/s40779-023-00488-2\u003c/li\u003e\n \u003cli\u003eAl-Wassia RK, Ghassal NM, Naga A, Awad NA, Bahadur YA, Constantinescu C. Optimization of Craniospinal Irradiation for Pediatric Medulloblastoma Using VMAT and IMRT. \u003cem\u003eJ Pediatr Hematol Oncol\u003c/em\u003e. 2015;37(7):e405-411. doi:10.1097/MPH.0000000000000418\u003c/li\u003e\n \u003cli\u003eGrill J, Sainte-Rose C, Jouvet A, et al. Treatment of medulloblastoma with postoperative chemotherapy alone: an SFOP prospective trial in young children. \u003cem\u003eLancet Oncol\u003c/em\u003e. 2005;6(8):573-580. doi:10.1016/S1470-2045(05)70252-7\u003c/li\u003e\n \u003cli\u003eCohen BH, Geyer JR, Miller DC, et al. Pilot Study of Intensive Chemotherapy With Peripheral Hematopoietic Cell Support for Children Less Than 3 Years of Age With Malignant Brain Tumors, the CCG-99703 Phase I/II Study. A Report From the Children\u0026rsquo;s Oncology Group. \u003cem\u003ePediatr Neurol\u003c/em\u003e. 2015;53(1):31-46. doi:10.1016/j.pediatrneurol.2015.03.019\u003c/li\u003e\n \u003cli\u003eAshley DM, Merchant TE, Strother D, et al. Induction chemotherapy and conformal radiation therapy for very young children with nonmetastatic medulloblastoma: Children\u0026rsquo;s Oncology Group study P9934. \u003cem\u003eJ Clin Oncol\u003c/em\u003e. 2012;30(26):3181-3186. doi:10.1200/JCO.2010.34.4341\u003c/li\u003e\n \u003cli\u003eFay-McClymont TB, Ploetz DM, Mabbott D, et al. Long-term neuropsychological follow-up of young children with medulloblastoma treated with sequential high-dose chemotherapy and irradiation sparing approach. \u003cem\u003eJ Neurooncol\u003c/em\u003e. 2017;133(1):119-128. doi:10.1007/s11060-017-2409-9\u003c/li\u003e\n \u003cli\u003eLevitch CF, Malkin B, Latella L, et al. Long-term neuropsychological outcomes of survivors of young childhood brain tumors treated on the Head Start II protocol. \u003cem\u003eNeurooncol Pract\u003c/em\u003e. 2021;8(5):609-619. doi:10.1093/nop/npab028\u003c/li\u003e\n \u003cli\u003eNeglia JP, Robison LL, Stovall M, et al. New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. \u003cem\u003eJ Natl Cancer Inst\u003c/em\u003e. 2006;98(21):1528-1537. doi:10.1093/jnci/djj411\u003c/li\u003e\n \u003cli\u003eLandberg TG, Lindgren ML, Cavallin-St\u0026aring;hl EK, et al. Improvements in the radiotherapy of medulloblastoma, 1946-1975. \u003cem\u003eCancer\u003c/em\u003e. 1980;45(4):670-678. doi:10.1002/1097-0142(19800215)45:4\u0026lt;670::aid-cncr2820450409\u0026gt;3.0.co;2-k\u003c/li\u003e\n \u003cli\u003eTokars RP, Sutton HG, Griem ML. Cerebellar medulloblastoma: results of a new method of radiation treatment. \u003cem\u003eCancer\u003c/em\u003e. 1979;43(1):129-136. doi:10.1002/1097-0142(197901)43:1\u0026lt;129::aid-cncr2820430120\u0026gt;3.0.co;2-y\u003c/li\u003e\n \u003cli\u003eErker C, Mynarek M, Bailey S, et al. Outcomes of Infants and Young Children With Relapsed Medulloblastoma After Initial Craniospinal Irradiation-Sparing Approaches: An International Cohort Study. \u003cem\u003eJ Clin Oncol\u003c/em\u003e. 2023;41(10):1921-1932. doi:10.1200/JCO.21.02968\u003c/li\u003e\n \u003cli\u003eKiltie AE, Lashford LS, Gattamaneni HR. Survival and late effects in medulloblastoma patients treated with craniospinal irradiation under three years old. \u003cem\u003eMed Pediatr Oncol\u003c/em\u003e. 1997;28(5):348-354. doi:10.1002/(sici)1096-911x(199705)28:5\u0026lt;348::aid-mpo4\u0026gt;3.0.co;2-h\u003c/li\u003e\n \u003cli\u003eSalceda-Rivera V, Tejocote-Romero I, Osorio DS, et al. Impact of treatment and clinical characteristics on the survival of children with medulloblastoma in Mexico. \u003cem\u003eFront Oncol\u003c/em\u003e. 2024;14:1376574. doi:10.3389/fonc.2024.1376574\u003c/li\u003e\n \u003cli\u003eMulhern RK, Merchant TE, Gajjar A, Reddick WE, Kun LE. Late neurocognitive sequelae in survivors of brain tumours in childhood. \u003cem\u003eLancet Oncol\u003c/em\u003e. 2004;5(7):399-408. doi:10.1016/S1470-2045(04)01507-4\u003c/li\u003e\n \u003cli\u003eLafay-Cousin L, Bouffet E, Hawkins C, Amid A, Huang A, Mabbott DJ. Impact of radiation avoidance on survival and neurocognitive outcome in infant medulloblastoma. \u003cem\u003eCurr Oncol\u003c/em\u003e. 2009;16(6):21-28. doi:10.3747/co.v16i6.435\u003c/li\u003e\n \u003cli\u003eRemke M, Ramaswamy V. Infant medulloblastoma - learning new lessons from old strata. \u003cem\u003eNat Rev Clin Oncol\u003c/em\u003e. 2018;15(11):659-660. doi:10.1038/s41571-018-0071-6\u003c/li\u003e\n \u003cli\u003eRobinson GW, Gajjar A. Genomics Paves the Way for Better Infant Medulloblastoma Therapy. \u003cem\u003eJ Clin Oncol\u003c/em\u003e. 2020;38(18):2010-2013. doi:10.1200/JCO.20.00593\u003c/li\u003e\n \u003cli\u003eKramer K, Pandit-Taskar N, Humm JL, et al. A phase II study of radioimmunotherapy with intraventricular 131 I-3F8 for medulloblastoma. \u003cem\u003ePediatr Blood Cancer\u003c/em\u003e. 2018;65(1). doi:10.1002/pbc.26754\u003c/li\u003e\n \u003cli\u003eKabir TF, Kunos CA, Villano JL, Chauhan A. Immunotherapy for Medulloblastoma: Current Perspectives. \u003cem\u003eImmunotargets Ther\u003c/em\u003e. 2020;9:57-77. doi:10.2147/ITT.S198162\u003c/li\u003e\n \u003cli\u003eVoskamp MJ, Li S, van Daalen KR, Crnko S, Ten Broeke T, Bovenschen N. Immunotherapy in Medulloblastoma: Current State of Research, Challenges, and Future Perspectives. \u003cem\u003eCancers (Basel)\u003c/em\u003e. 2021;13(21):5387. doi:10.3390/cancers13215387\u003c/li\u003e\n \u003cli\u003eRusert JM, Juarez EF, Brabetz S, et al. Functional Precision Medicine Identifies New Therapeutic Candidates for Medulloblastoma. \u003cem\u003eCancer Res\u003c/em\u003e. 2020;80(23):5393-5407. doi:10.1158/0008-5472.CAN-20-1655\u003c/li\u003e\n \u003cli\u003eRutkowski S, Gerber NU, von Hoff K, et al. Treatment of early childhood medulloblastoma by postoperative chemotherapy and deferred radiotherapy. \u003cem\u003eNeuro Oncol\u003c/em\u003e. 2009;11(2):201-210. doi:10.1215/15228517-2008-084\u003c/li\u003e\n \u003cli\u003eZeltzer PM, Boyett JM, Finlay JL, et al. Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: conclusions from the Children\u0026rsquo;s Cancer Group 921 randomized phase III study. \u003cem\u003eJ Clin Oncol\u003c/em\u003e. 1999;17(3):832-845. doi:10.1200/JCO.1999.17.3.832\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"childs-nervous-system","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cnsy","sideBox":"Learn more about [Child's Nervous System](http://link.springer.com/journal/381)","snPcode":"381","submissionUrl":"https://submission.nature.com/new-submission/381/3","title":"Child's Nervous System","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"medulloblastoma, radiation therapy, neurodevelopment, gross total resection, outcomes","lastPublishedDoi":"10.21203/rs.3.rs-9361013/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9361013/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eObjective\u003c/b\u003e\u003c/p\u003e \u003cp\u003eMedulloblastomas (MB) are the most common primary central nervous system malignancy in children (WHO Grade IV). While MB is commonly treated with cerebrospinal irradiation (CSI) in older children, potential neurodevelopmental complications have led to consideration of surgery and chemotherapy alone for children under 4. However, current guidelines lack a definitive recommendation for this patient population. We conducted a retrospective analysis of the SEERS 17 database (2000\u0026ndash;2022) to investigate radiotherapy for MB patients under the age of 4.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003e1:1 Propensity score matching (PSM) with a caliper of 0.03 was utilized to account for confounding variables. Kaplan Meier (KM) curves were computed for matched patients, followed by univariate cox survival analysis for both overall survival (OS) and cancer specific survival (CSS). A multivariate binomial regression model assessed determinants of radiation treatment selection. All statistical analyses were conducted using a significance threshold of α\u0026thinsp;=\u0026thinsp;0.05.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003e375 patients under 4 with surgically resected MB were identified for analysis. The proportion receiving adjuvant radiation demonstrated a decrease with time (r=-0.77). Following PSM, 111 patients were identified for both the radiation treatment and no radiation treatment groups. KM analysis demonstrated no significant difference between the groups in CSS (p\u0026thinsp;=\u0026thinsp;0.12) or OS (p\u0026thinsp;=\u0026thinsp;0.063). The propensity score weighted Cox model demonstrated that radiation was associated with significantly improved OS (HR\u0026thinsp;=\u0026thinsp;0.56, 95% CI 0.41\u0026ndash;0.78, p\u0026thinsp;=\u0026thinsp;0.0004) and improved CSS (HR\u0026thinsp;=\u0026thinsp;0.57, 95% CI 0.40\u0026ndash;0.80, p\u0026thinsp;=\u0026thinsp;0.001), with consistent direction across both endpoints. In binomial regression, older age (β\u0026thinsp;=\u0026thinsp;1.36, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and earlier year of diagnosis (β = \u0026minus;\u0026thinsp;0.08, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were associated with increased radiation receipt (Δ Deviance\u0026thinsp;=\u0026thinsp;52.3, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; AIC\u0026thinsp;=\u0026thinsp;601.3).\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eAdjuvant radiation in MB patients under 4 was associated with improved OS. Radiation use for this population has decreased over time, with older age predicting greater treatment receipt. Prospective validation and reduced\u0026mdash;dose radiation approaches are critical to ensure consistent survival benefit and minimal complications.\u003c/p\u003e","manuscriptTitle":"Efficacy and Determinants of Adjuvant Radiation Therapy for Medulloblastoma Patients under 4: A Propensity Score Matched National Cohort Study of Survival Outcomes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-12 14:27:32","doi":"10.21203/rs.3.rs-9361013/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"161451070573202112533822815507653712870","date":"2026-05-04T12:35:47+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-05-04T11:40:25+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-10T08:04:34+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-10T08:03:34+00:00","index":"","fulltext":""},{"type":"submitted","content":"Child's Nervous System","date":"2026-04-08T20:43:40+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"childs-nervous-system","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cnsy","sideBox":"Learn more about [Child's Nervous System](http://link.springer.com/journal/381)","snPcode":"381","submissionUrl":"https://submission.nature.com/new-submission/381/3","title":"Child's Nervous System","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"bfd2b8b2-4510-4c9d-aedf-460a921918aa","owner":[],"postedDate":"May 12th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"161451070573202112533822815507653712870","date":"2026-05-04T12:35:47+00:00","index":6,"fulltext":""},{"type":"reviewersInvited","content":"1","date":"2026-05-04T11:40:25+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-12T14:27:32+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-12 14:27:32","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9361013","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9361013","identity":"rs-9361013","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}