Tony H. Truong

Background and Aims: Infant bone and soft tissue neoplasms present distinct clinical challenges and lack large‐scale data to inform treatment decisions. This study aims to characterize bone and soft tissue neoplasms in infants in Canada and to compare their outcomes with those of older pediatric patients. Methods: We conducted a retrospective population‐based cohort study using the Cancer in Young People in Canada (CYP‐C) database, including all children p = 0.003), inferior 1‐year (63.7% vs. 81.5%; p < 0.001) and 5‐year OS (56.9% vs. 62.0%; p < 0.001), and a lower but non‐significant 5‐year CIR (26.3% vs. 38.4%; p = 0.19). After adjustment for tumor subtype and metastatic status, infancy remained independently associated with poorer OS (adjusted HR 1.61, 95% confidence interval [CI] 1.13–2.31; p = 0.009). Conclusion: Despite no increased risk of relapse, infants with bone and soft tissue neoplasms have significantly poorer survival than older children, primarily due to a substantially higher risk of TRM.

The optimal busulfan exposure window in pediatric patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (HSCT) remains to be defined. We identify this window for patients receiving busulfan within the prospective international, randomized controlled phase 3 ALLSCTped 2012 FORUM trial. We included 145 participants receiving fludarabine-busulfan-thiotepa conditioning, with available busulfan plasma levels. Busulfan exposure was estimated using a validated pediatric population pharmacokinetic model. Primary outcomes were event-free survival (EFS) and graft-versus-host disease-free relapse-free survival (GRFS). Patients were aged between 0.5 and 19.5 years, with a median follow-up of 5.0 years. The optimal busulfan exposure was defined as area under busulfan concentration curve (cAUC) of 73.3 to 98.0 mg.h/L based on EFS and GRFS. Patients with nonoptimal exposure had lower EFS (hazard ratio [HR], 1.93; p = 0.008) and GRFS (HR, 2.01; p = 0.002). Underexposure (cAUC 98.0 mg.h/L) with an increased risk of treatment-related toxicities and graft-versus-host disease. Patients with optimal busulfan exposure showed no differences in EFS, GRFS, overall survival, or relapse with post hoc matched total-body irradiation (TBI) recipients (n = 51 in each group). This study identifies a favorable busulfan exposure window for pediatric patients with ALL undergoing HSCT from an HLA-matched donor. Therapeutic drug monitoring for optimized personalized busulfan dosing improves HSCT outcomes and might be validated for use as an alternative to irradiation. This trial was registered at EudraCT as 2012-003032-22 and on www.ClinicalTrials.gov as NCT01949129.

PURPOSE: Public reporting of health care outcomes can have unintended effects such as inappropriate risk aversion in patient selection. METHODS: The center-specific survival analysis annually assigns all hematopoietic cell transplantation (HCT) centers in the United States a +1, −1, or 0 score for observed outcomes that are above, below, or within a center-specific predicted range of outcome. For each index year (2012-2016), centers receiving a −1 score after 0 scores in the preceding 2 years were compared with contemporaneous centers with as-predicted outcomes (0 score). Changes in the patient population characteristics in the 3 years before versus the 3 years after the index years were compared between the newly below-expected centers (NBCs) and the controls. A multivariate model adjusted for baseline patient population characteristics and center volume. RESULTS: No differences in patient selection behavior were identified when comparing the NBCs with the controls across eight key patient population characteristics. For the statistically modeled (predicted) 1-year overall survival (OS), reflecting a holistic measure of centers' patient population risk, we observed no statistically significant difference in change (−0.23% [95% CI, −1.4 to 0.9]; P = .70). The observed OS increased in both NBCs and controls by 0.9% and 4.5%, respectively, without statistically significant difference in change. CONCLUSION: Centers receiving a −1 score were not observed to deviate significantly from patient selection trends in the HCT field. These findings suggest that public reporting of HCT outcomes in the United States does not result in unintended bias against HCT for high-risk patients.

Background: Little is known about children with cancer who participate in early phase (phase 1/2) oncology trials toward the end of life (EOL). The authors sought to describe the proportion of Canadian children with cancer who participate in trials in their last 90 days, explore predictors of enrollment, describe these trials and key EOL outcomes.Methods: This retrospective cohort study used data from the Cancer in Young People in Canada (CYP‐C) database, a national population‐based registry. The study included Canadian children and adolescents with cancer 0–20 years old at death, who died from 2001 to 2021. We performed logistic regression to explore the relationships between diagnosis‐related factors, treatment‐related factors, demographic factors, and study enrollment.Results: Of 3125 children and adolescents who died, 140 (4.5%) met study criteria. Patients with leukemia or lymphoma (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.33–0.87) or a solid tumor (OR, 0.48; 95% CI, 0.29–0.79) enrolled less frequently than those with central nervous system tumors. Previous trial enrollment (OR, 3.02; 95% CI, 2.43–3.77), and initial treatment in a major early phase study center (OR, 1.65; 95% CI, 1.14–2.4) were associated with enrollment. Patients in the lowest census‐based income quintiles (quintiles 1–2) enrolled less frequently than those in the highest quintiles (3–5) (OR, 0.56; 95% CI, 0.37–0.84).Conclusions: A small proportion of children and adolescents participate in early phase trials toward EOL. Diagnosis, treatment‐related, and socioeconomic factors are associated with non‐enrollment. Clinicians, researchers, and policy developers should consider and address the possible impact of socioeconomic and other factors on access to studies, to ensure equitable access for diverse populations.

Background: Childhood obesity can result in adverse health outcomes. The objectives of this study were to describe the prevalence of obesity and determine the association between obesity at cancer diagnosis and event‐free survival (EFS) and overall survival (OS) in children diagnosed with cancer in Canada.Methods: The authors conducted a retrospective cohort study using the Cancer in Young People in Canada database, including all children with newly diagnosed cancer aged 2–18 years across Canada from 2001 to 2020. Obesity was defined as age‐adjusted and sex‐adjusted body mass index greater than or equal to the 95th percentile. Univariate and multivariable Cox proportional hazards models compared EFS and OS between patients with and without obesity at diagnosis.Results: In total, 11,291 patients were included, of whom 10.5% were obese at diagnosis. In multivariable models controlling for age, sex, ethnicity, neighborhood income quintile, treatment era, and cancer categories, obesity at diagnosis was independently associated with inferior EFS (adjusted hazard ratio [aHR], 1.16; 95% confidence interval [CI], 1.02–1.32; p = .02) and OS (aHR, 1.29; 95% CI, 1.11–1.49; p = .001). The adverse prognostic impact of obesity was particularly notable for acute lymphoblastic leukemia (ALL) and central nervous system (CNS) tumors. In children with ALL (n = 3458), obesity remained associated with inferior EFS (aHR, 1.55; p = .002) and OS (aHR, 1.75; p = .002) in multivariable analysis. In patients with CNS tumors (n = 2458), obesity was also associated with inferior EFS (aHR, 1.38; p = .008) and OS (aHR, 1.47; p = .004).Conclusions: In this population‐based study, obesity at cancer diagnosis was independently associated with inferior survival across the entire cohort, and prominently in children with ALL and CNS tumors.

Background/Objectives: Vaccine hesitancy among immunocompromised patients is complex and not well understood. This study aimed to determine the rate of COVID-19 vaccine hesitancy among pediatric oncology and bone marrow transplant (BMT) patients and to understand associated factors. Methods: Parents of patients (≤18 years) with cancer or post-BMT completed the Parent Attitudes about Childhood Vaccines Survey. A COVID-19 vaccine hesitancy score (VHS-COVID) was calculated from 0 to 100 (higher scores indicating increasing hesitancy). A small group of patients (patients older than 15 years) were also surveyed directly. Results: Among 113 parent respondents, the majority were female (58%) and at least college/university educated (78%). The majority (73%) of patients had cancer (61% leukemia/lymphoma, 37% solid/CNS tumors), while 27% had received BMT for malignant and non-malignant conditions. Only 48% of patients had been vaccinated against COVID-19, compared to 88% of parents. Ineligibility due to phase of cancer/BMT treatment (27%), vaccine hesitancy (24%), and age (24%) were the top three reasons for not vaccinating against COVID-19. Only 13% of parents said they would “definitely vaccinate” if their child became eligible. VHS-COVID scores were higher for parents of patients in surveillance versus active therapy (mean 61 vs. 48; p = 0.03). Parents who had received fewer COVID-19 vaccine doses (0–1 vs. ≥2) were more hesitant toward all vaccines (p = 0.0002), COVID-19 vaccines (p = 0.0003), and influenza vaccines (p = 0.005). Conclusions: Vaccine hesitancy is common among this population and was demonstrated through beliefs (hesitancy scores) as well as vaccine uptake. Future work should focus on education targeting vaccine eligibility and engaging with vaccine hesitant families in the immunocompromised community.

Background: Hematopoietic cell transplantation (HCT) is an established therapy for hematologic malignancies and serious non-malignant blood disorders. Despite its curative potential, HCT is associated with substantial toxicity and health resource utilization. Effective delivery of HCT requires complex hospital-based care, which limits the number of HCT centres in Canada. In Canada, the quantity, indications, temporal trends, and outcomes of patients receiving HCT are not known. Methods: A retrospective cohort study of first transplants reported to the Cell Therapy Transplant Canada (CTTC) registry between 2000 and 2019. We determined overall survival (OS) and non-relapse mortality (NRM), categorizing the cohort into early (2000–2009) and later (2010–2019) eras to investigate temporal changes. Results: Of 18,046 transplants, 7571 were allogeneic and 10,475 were autologous. Comparing the two eras, allogeneic transplants increased in number by 22.3%, with greater use of matched unrelated donors in the later era. Autologous transplants increased by 10.9%. Temporal improvements in NRM were observed in children and adults. OS improved in pediatric patients and in adults receiving autologous HCT. In adults receiving allogeneic HCT, OS was stable despite the substantially older age of patients in the later era. Interpretation: HCT is an increasingly frequent procedure in Canada which has expanded to serve older adults. Noted improvements in NRM and OS reflect progress in patient and donor selection, preparation for transplant, and post-transplant supportive care. In allogeneic HCT, unrelated donors have become the most frequent donor source, highlighting the importance of the continued growth of volunteer donor registries. These results serve as a baseline measure for quality improvement and health services planning in Canada.

Background: Hematopoietic cell transplantation (HCT) is an established therapy for hematologic malignancies and serious non-malignant blood disorders. Despite its curative potential, HCT is associated with substantial toxicity and health resource utilization. Effective delivery of HCT requires complex hospital-based care, which limits the number of HCT centers in Canada. In Canada, the quantity, indications, temporal trends, and outcomes of patients receiving HCT are not known. Methods: A retrospective cohort study of first transplants reported to the Cell Therapy Transplant Canada (CTTC) registry between 2000 and 2019. We determined overall survival (OS) and non-relapse mortality (NRM), categorizing the cohort into early (2000-2009) and later (2010-2019) eras to investigate temporal changes. Results: Of 18,046 transplants, 10,475 were allogeneic and 7,571 were autologous. Comparing the two eras, allogeneic transplants increased in number by 22.3%, with greater use of matched unrelated donors in the later era. Autologous transplants increased by 10.9%. Temporal improvements in NRM were observed in children and adults. OS improved in pediatric patients and in adults receiving autologous HCT. In adults receiving allogeneic HCT, OS was stable despite the substantially older age of patients in the later era. Interpretation: HCT is an increasingly frequent procedure in Canada which has expanded to serve older adults. Noted improvements in NRM and OS reflect progress in patient and donor selection, preparation for transplant, and post- transplant supportive care. In allogeneic HCT, unrelated donors have become the most frequent donor source, highlighting the importance of continued growth of volunteer donor registries. These results serve as a baseline measure for quality improvement and health services planning in Canada.