Survivors of pediatric brain tumors (BT) experience significant, long-term adverse treatment-related effects, such as social deficits—which can impact academic achievement, quality of life, and daily adaptive functioning. Affective processing remains underexplored. This study investigated social affective processing in survivors compared to healthy children (HC), identified clinical and sociodemographic factors that may be related to affective processing, and explored whether cognitive-executive function mediates these relationships. Survivors (N = 33, 54.5

Abstract Childhood brain tumor (BT) survivors treated with cranial radiation therapy (RT) frequently experience neurocognitive late effects, yet dose-sensitive neuroanatomical substrates of social–cognitive vulnerability remain uncharacterized. This exploratory study mapped region-specific RT dosimetry to social cognition, white matter integration, and executive/behavioral functioning. The RT sample included 14 participants (mAge=14.33, SD = 3.47;57.1% male) recruited from Alberta Children’s Hospital’s Long-Term Survivor Clinic. Neuropsychological assessment included the Wechsler Intelligence Scale for Children–Fifth Edition (WISC-V) indices of Working Memory and Processing Speed and the Test for the Evaluation of Emotions and Socialisation (TEEMS). Parent-reports measuring adaptive, executive and socioemotional functioning were also included. Planned diffusion tensor imaging will further characterize dose-sensitive white matter by quantifying diffusion anisotropy. Exploratory associations (Kendall’s τ and Spearman’s ρ) and dose-threshold contrasts (<30Gy vs ≥ 30Gy) were used. Higher right hippocampal and infratentorial mean doses related to poorer auditory working memory (τ and ρ, ps<.05;τ p< .05;ρ p<.01). Higher left amygdala and bilateral temporal-lobe doses related to poorer simple auditory digit registration (τ/ρ,ps< .05). For social cognition, slower social labeling performance related to left hippocampal and left temporal-lobe dose (τ/ρ, ps≤ .05), bilateral amygdala dose (τ ps< .05;ρ ps< .01), and sella mean dose (p<.05). Emotion recognition also associated with sella dose (ρ p<.05). Higher total dose correlated with poorer cognitive flexibility and attentional control (ps≤.01), and broader social and functional vulnerabilities (ps<.05) via parent-report. Dose-threshold contrasts (<30 vs ≥ 30Gy) indicated clinically meaningful impairments to rapid emotion labeling among groups that received more radiation for left temporal, amygdalae, hypothalamus, sella, and supratentorial regions while preserved performance was observed in < 30 Gy groups. Findings implicate hippocampal, temporal, amygdalae, infratentorial, sellar, and supratentorial dose exposure in auditory working-memory and rapid social-judgment with broader executive/adaptive sequelae. These patterns may inform region-sparing RT planning. Dose-sensitive white matter pathways may emerge via diffusion analysis.

Background: Survivors of cancer in adolescence and young adulthood are at increased risk for subsequent primary neoplasms, but studies using Canadian data are limited. We sought to quantify the risk of subsequent primary neoplasms among survivors of cancer in adolescence and young adulthood in Alberta, Canada. Methods: The Alberta Adolescent and Young Adult Cancer Survivor Study is a retrospective, population-based cohort of people aged 15 to 39 years with a neoplasm first diagnosed between 1983 and 2017. We assessed risks of subsequent primary neoplasms overall and after 5-year survival, calculated as standardized incidence ratios (SIRs) and absolute excess risks (AERs) per 10 000 person-years, compared with expected general population rates, with up to 30 years of follow-up. Results: Among 24 459 people who had cancer in adolescence and young adulthood, 1442 had subsequent primary neoplasms, 1129 of which occurred after 5-year survival. The risk of subsequent primary neoplasm overall and after 5-year survival was similar (SIR 2.2, 95% confidence interval [CI] 2.1 to 2.4 v. 2.0, 95% CI 1.9 to 2.2; AER 31.7, 95% CI 28.7 to 34.6 v. 35.7, 95% CI 31.6 to 39.8 per 10 000 person-years). Most subsequent primary neoplasms were breast, digestive, hematopoietic, or respiratory cancers. After 5-year survival, the 30-year cumulative incidence of a subsequent primary neoplasm was 17.7% (95% CI 16.5% to 18.9%), with incidence highest among survivors of cancers of the oral cavity, lip, or pharynx (28.9%, 95% CI 18.9% to 39.6%), breast cancer (27.3%, 95% CI 23.7% to 30.9%), colon cancer (23.5%, 95% CI 14.2% to 34.1%), and Hodgkin lymphoma (22.7%, 95% CI 18.2% to 27.6%). Interpretation: Survivors of cancer in adolescence and young adulthood are at increased risk for nearly all types of subsequent primary neoplasms assessed. Early, risk-based screening may be warranted, particularly for screen-detectable cancers for which risks are greatest.

Background: While research shows childhood cancer survivors experience elevated subsequent primary neoplasm (SPN) and premature mortality risks, few studies have included contemporary survivors. Methods: This study quantifies the risk of SPNs and mortality among modern survivors of childhood cancer. Utilizing a retrospective, population-based cohort of individuals diagnosed with cancer before the age of 18 in Alberta, Canada (2001-2018), we evaluated their risks of SPNs and mortality compared to the general population in Alberta, overall and after 5-year survival, using standardized mortality and incidence ratios, and absolute excess risks per 10,000 person-years. Results: Among 2581 survivors, including 1385 5-year survivors, 50 individuals developed at least one SPNs and 408 deaths were observed, with 21 SPNs and 38 deaths occurring after 5-year survival. The SPN incidence was 13.3- (95% CI: 9.8-17.5) and 10.0-fold (95% CI: 6.2-15.2) higher than expected overall and in 5-year survivors, respectively, with risks varying depending on the treatment received. For mortality, survivors experienced 62.5-fold (95% CI: 56.5-68.8) higher mortality than expected overall, equating to 233.9 (95% CI: 210.8-257.0) excess deaths per 10,000 person-years, with corresponding risks among 5-year survivors at 10.9 (95% CI: 7.7-15.0) and 43.8 (95% CI: 28.4-59.1), respectively. The excess deaths were predominantly due to recurrence/progression (89.9% overall, 66.4% in 5-year survivors), with SPNs and non-neoplastic causes contributing more excess deaths with increasing follow-up time. Risks for mortality included treatment and cancer type. Conclusions: Contemporary childhood cancer survivors in Alberta experience substantial excess SPNs and mortality, highlighting the need for long-term surveillance and tailored risk mitigation interventions.

Importance:Radiotherapy for breast cancer exposes the heart to incidental radiation, and historical data have shown a dose-dependent increase in associated cardiac events. Although whole-heart dose metrics are commonly used for risk assessment, emerging evidence suggests that dose to the left anterior descending coronary artery (LAD) may better capture risk. Objective:To compare the ability of heart and LAD radiation dose metrics to predict cardiac risk after breast radiotherapy. Design, Setting, and Participants:This was a cross-sectional study of patients with breast cancer who were treated with either 3-dimensional conformal or intensity-modulated radiotherapy from 2008 to 2018 at a tertiary care center in Canada. The primary analysis included patients with left-sided breast cancer. Cardiac events were assessed using longitudinal follow-up data. Dosimetry was derived from computed tomography plans using automated segmentation and converted to equivalent dose in 2-Gy fractions (EQD2). Data were analyzed from September 2024 to April 2026. Main Outcomes and Measures:Adverse cardiac events defined as myocardial infarction or hospital admission or emergency department visit for unstable angina (ie, acute coronary syndrome), arrhythmia, heart failure, pericarditis, or myocarditis. The incidence of coronary angiography and coronary revascularization was also captured as coronary artery disease (CAD). Discrimination for dose metrics was performed with receiver operator characteristic curves and competing-risks regression (Fine and Gray), adjusted for cardiovascular risk factors. Results:The analysis included 4908 patients with breast cancer of whom 2223 had left-sided breast cancer. During a median (IQR) follow-up period of 10.8 (8.4-13.1) years, cumulative incidence of cardiac event or CAD was 5.0 (95% CI, 4.1-6.0) at 10 years. A data-driven cut point analysis identified 12 Gy EQD2 as the maximum LAD dose that best stratified risk. Among patients with left-sided breast cancer, maximum LAD dose (concordance [C] index, 0.58; 95% CI, 0.52-0.64) discriminated better than mean heart dose (C index, 0.53; 95% CI, 0.47-0.60). In multivariable analysis, maximum LAD of 12 Gy or greater was independently associated with higher cardiac risk (subdistribution hazard ratio = 1.81; 95% CI, 1.04-3.16; P = .04), whereas mean heart dose of 2 Gy or greater was not associated (P = .99). For clinical context, the 12-Gy EQD2 for maximum LAD dose corresponds to a physical dose of approximately 10.5 Gy for 42.5 Gy in 16 fractions and 7 Gy for 26 Gy in 5 fractions. Conclusions and Relevance:In this cross-sectional study of heart-sparing breast radiotherapy, LAD dose was associated with cardiac events, whereas whole-heart metrics was not. These findings support LAD-based planning and respiratory motion management to reduce long-term cardiovascular risk in patients with breast cancer undergoing radiotherapy.

Radiation therapy serves as an effective treatment modality for paediatric solid and central nervous system (CNS) tumours. Proton beam therapy (PBT) offers steeper dose gradients than conventional radiation therapy, reducing the dose to surrounding normal tissue dose. Unfortunately, PBT is unavailable in Canada and children are referred to the United States for treatment. AIMS:We describe the Canadian paediatric cancer population receiving PBT and their outcomes. MATERIALS AND METHODS:Patient demographics, treatment details, and survival outcomes were extracted for all paediatric patients from 12 of 13 provinces/territories. Eligibility criteria included: diagnosis of cancer at age ≤20 years between 2001-2021 and administration of curative-intent PBT. Temporal trends in PBT referrals were modelled using Poisson regression, and overall survival (OS) was estimated with the Kaplan-Meier method. RESULTS:Of 314 eligible children (55.7% male), most patients were from Quebec (26.4%), British Columbia (24.8%), Alberta (22.6%), and Ontario (21.0%). The median age of cancer diagnosis was 7.3 years. The most patients had CNS tumours (69.4%), with medulloblastoma, craniopharyngioma, and ependymoma being the most frequently represented. Most common solid tumours included rhabdomyosarcoma, neuroblastoma, and Ewing's sarcoma. Provinces/territories usually referred patients to PBT centres close in geographical proximity. Referrals have increased at a rate of 16% per year between 2001 and 2022. For children aged <15 years, five-year OS was 85.8% and 73.1% for CNS and solid tumours, respectively. CONCLUSION:Based on our data, there is a true need for the establishment of PBT centres in Canada for the treatment of cancers in children.

The growing number of breast cancer survivors is expected to increase the absolute number of locoregional recurrences requiring management, necessitating improvements in treating recurrences or tumours that occur within the initial radiation field (IFR). However, there are no guidelines on reirradiation (RT2) for breast cancer IFRs. We aimed to investigate locoregional practice patterns and outcomes. We retrospectively identified patients who received adjuvant RT1 for resected breast cancer and subsequently received curative-intent RT2 for IFRs at two large tertiary centres. A chart review obtained treatment, patient, and tumour characteristics. Descriptive statistics were calculated to characterize practice patterns, toxicity, and survival outcomes. Thirty-five patients met inclusion criteria across 18 years, with mean follow-up time of 43 months. Median time from RT1 to progression was 70.1 months. Most IFRs were in the breast or chest wall alone (48.6%). Regional nodal irradiation (RNI) was given in 23% of RT1 and 48.6% of RT2. Complete field overlap occurred in 60% of patients. Ten patients (28.6%) had a second recurrence (i.e., after RT2). Five-year OS was 65.4%, the median OS was not reached, and the mean OS was 73.7 months (95% CI 59.8-87.7 months). Freedom from recurrence (after RT2) was 71%. Shorter time to initial recurrence was associated with second recurrence (p = 0.018), and second recurrence was found to be predictive of death (p < 0.001). Four (11.4%) patients developed fibrosis, 75% of which developed after RT1. Eight (22.9%) patients developed lymphedema, 75% of which developed after RT1, all of which were documented as stable after RT2. Managing breast cancer IFRs with RT2 appears to be a feasible approach with reasonably consistent practice patterns in appropriately selected patients. Toxicity appears to be driven by the initial treatment course, and survival outcomes are acceptable.

BACKGROUND:Whole abdominal radiotherapy (WART) is utilized in children, adolescents, and young adults with intra-abdominal sarcoma, but efficacy and toxicity are uncertain. METHODS:Sarcoma patients diagnosed at ≤39 years of age between 1998 and 2023 who received WART were identified from a national registry. Patient and tumor characteristics, treatment, response, and survival outcomes were assessed. RESULTS:Twenty patients with desmoplastic small round cell tumor (DSRCT) (n = 7), rhabdomyosarcoma (RMS) (n = 6), Ewing sarcoma, rhabdoid tumor, endometrial stromal tumor (each n = 1), and sarcoma not-otherwise-specified (NOS) (n = 4) were included. Among 17 patients who received WART as part of upfront therapy, 16 had abdominal metastatic disease (94.1%) (peritoneal deposits n = 9, malignant ascites n = 8 [including two with both peritoneal deposits and malignant ascites] and liver metastases n = 1), while one was initially localized. Median WART dose was 22.5 Gy (range: 10.5-30); median kidney and liver doses were 14.9 Gy (range: 7.7-20.7) and 21.0 Gy (range: 13.1-27.7), respectively. Three patients developed Grade 3 acute toxicity; diarrhea (n = 2) or elevated creatinine (n = 1); two RMS patients developed second malignancies. Two-year overall and progression-free survival estimates were 100% and 80% (95% confidence interval [CI]: 51.6%-100%) in RMS; 62.5% (95% CI: 32%-100%) and 50% (95% CI: 22.5%-100%) in DSRCT. Five-year cumulative incidence of abdominal recurrence was 33.3% (95% CI: 11.4%-57.3%) with WART failure in DSRCT (n = 2) and sarcoma NOS (n = 1). Three patients received WART following relapse; all recurred; two within the WART field. CONCLUSIONS:WART is well tolerated among young sarcoma patients and provides meaningful local disease control when utilized in front-line adjuvant therapy.

PURPOSE:The study objective is to improve breast radiation therapy clinical workflows through a quality improvement approach rooted in implementation and improvement science methodologies. This study aims to demonstrate the effectiveness of these data-driven, multidisciplinary processes in optimizing complex clinical processes within radiation oncology. METHODS AND MATERIALS:A multidisciplinary stakeholder team applied an improvement science methodology to identify the root cause of inefficiencies in a pretreatment breast radiation therapy workflow. The intervention involved redesigning the task sequence and implementing an automated breast treatment planning solution to replace manual planning. The study evaluated the outcome measure of the target contouring time by the radiation oncologist and the treatment planning time by the medical dosimetrist. The outcome measures for 3 cohorts were analyzed: (1) the initial cohort with manual planning prior to any process change, (2) the pilot cohort with a limited stakeholder team for rapid change cycles with the modified clinical workflow and automated planning solution, and (3) a comprehensive rollout with the entire clinical team. The balancing quality measures of dosimetric compliance to dose-volume histogram planning objectives were also assessed across the 3 cohorts. RESULTS:From 2020 to 2022, 515 patients were included in the analysis. The task times from the initial cohort to the comprehensive rollout cohort were 0.2 (± 0.07) hours and 0.2 (± 0.03) hours for radiation oncologist contouring time and 8 (± 4) hours and 4 (± 1) hours for medical dosimetrist planning time, respectively. At the conclusion of the comprehensive rollout, total professional task time was decreased, and treatment plan quality was maintained. The approach successfully scaled from the smaller stakeholder team to the entire clinical workforce, demonstrating the effectiveness of implementation and improvement science methodologies. CONCLUSIONS:This study provides a comprehensive description and evaluation of a data-driven, sustainable process change in a multidisciplinary breast radiation therapy workflow. The methodology used serves as a model for clinical workflow optimization across radiation oncology settings.

Radiotherapy is important for treating pediatric CNS tumours. The main modalities include photon therapy and PBT. PBT offers potential advantages over photon therapy in children since its precise dose control can limit long-term side effects. However, Canadian patients needing PBT are referred to the United States (US) because PBT is unavailable in Canada. We aimed to describe PBT use and outcomes over time for Canadian pediatric patients with CNS tumours. Patient demographics, treatment characteristics, and outcomes were extracted from medical records of patients from 10/13 Canadian provinces/territories. Patients diagnosed with a CNS tumour at ≤20 years old between 2001-2021 who received curative-intent PBT were included. PBT plans were compared using Fisher’s exact or Kruskal-Wallis rank sum tests. Overall survival (OS) was estimated using the Kaplan-Meier method. Of 195 patients (59.0% male) included in the study, majority were from Alberta (28.7%), Quebec (26.7%), British Columbia (22.6%), and Ontario (20.5%). Median age at diagnosis was 8.0 years. Most tumours (77.9%) were non-metastatic. Medulloblastoma was the most common diagnosis (30.8%). Provinces/territories referred patients to proton centres in the same geographical regions, except Alberta (74.5% referred to Florida). Referral numbers have increased ~180%/year since 2011. Median time from diagnosis to PBT was 126 days [11-5236] for all patients, and 36 days [21-1313] for medulloblastoma. Radiation doses, irradiation site, therapy duration, and time to treatment were not different (p≥0.2) across all PBT facilities for medulloblastoma. 5-year OS were 86.8% and 73.0% for the PBT study population and the Cancer in Young People-Canada reference population, respectively, in those aged <15 years. Given the unavailability of PBT in Canada, pediatric CNS tumour patients were referred to US PBT facilities close in proximity. Further studies are needed to better understand provincial referral patterns and barriers to equitable PBT access across Canada.