Abstract
Participants in clinical trials may experience benefits associated with new therapeutic strategies as well as tight adherence to best supportive care practices. To investigate whether participation in a clinical trial is associated with improved survival among children with neuroblastoma and investigate potential recruitment bias of patients in clinical trials. This cohort study included pediatric patients with intermediate- or high-risk neuroblastoma in North American studies who were included in the International Neuroblastoma Risk Group Data Commons and who received a diagnosis between January 1, 1991, and March 1, 2020. Enrollment in a clinical trial. Event-free survival and overall survival (OS) of patients with intermediate- or high-risk neuroblastoma enrolled in an up-front Children's Oncology Group (COG) clinical trial vs a biology study alone were analyzed using log-rank tests and Cox proportional hazards regression models. The racial/ethnic composition and the demographic characteristics of the patients in both groups were compared. The cohort included 3058 children with intermediate-risk neuroblastoma (1533 boys [50.1%]; mean [SD] age, 10.7 [14.7] months) and 6029 children with high-risk neuroblastoma (3493 boys [57.9%]; mean [SD] age, 45.8 [37.4] months) who were enrolled in a Children's Oncology Group or legacy group neuroblastoma biology study between 1991 and 2020. A total of 1513 patients with intermediate-risk neuroblastoma (49.5%) and 2473 patients with high-risk neuroblastoma (41.0%) were also enrolled in a clinical trial, for a cohort total of 3986 of 9087 children (43.9%) enrolled in a clinical trial. The prevalence of prognostic markers for the clinical trial and non-clinical trial cohorts differed, although representation of patients from racial/ethnic minority groups was similar in both cohorts. Among patients with intermediate-risk neuroblastoma, OS was higher among those who participated in a clinical trial compared with those enrolled only in a biology study (OS, 95% [95% CI, 94%-96%] vs 91% [95% CI, 89%-94%]; P = .01). Among patients with high-risk neuroblastoma, participation in a clinical trial was not associated with OS (OS, 38% [95% CI, 35%-41%] in the clinical trial group vs 41% [95% CI, 38%-44%] in the biology study group; P = .23). Approximately 44% of patients in this large cohort of patients with neuroblastoma were enrolled in up-front clinical trials. Compared with children not enrolled in clinical trials, a higher prevalence of favorable prognostic markers was identified among patients with intermediate-risk neuroblastoma enrolled in clinical trials, and unfavorable features were more prevalent among patients with high-risk neuroblastoma enrolled in clinical trials. No evidence of recruitment bias according to race/ethnicity was observed. Participation in a clinical trial was not associated with OS in this cohort, likely reflecting the common practice of treating nontrial participants with therapeutic and supportive care regimens used in a previous therapeutic trial.
Highlights
Therapeutic clinical trials have enabled the development of new approaches that have improved the survival of patients with cancer.[1,2,3,4] patients receiving experimental regimens in therapeutic clinical trials may experience benefits associated with new treatment strategies, those randomly assigned to receive the standard of care may experience benefits associated with strict adherence to treatment schedules, dosing, and supportive care required by study protocols
Among patients with intermediate-risk neuroblastoma, overall survival (OS) was higher among those who participated in a clinical trial compared with those enrolled only in a biology study (OS, 95% [95% CI, 94%-96%] vs 91% [95% CI, 89%-94%]; P = .01)
Compared with children not enrolled in clinical trials, a higher prevalence of favorable prognostic markers was identified among patients with intermediate-risk neuroblastoma enrolled in clinical trials, and unfavorable features were more
Summary
Therapeutic clinical trials have enabled the development of new approaches that have improved the survival of patients with cancer.[1,2,3,4] patients receiving experimental regimens in therapeutic clinical trials may experience benefits associated with new treatment strategies, those randomly assigned to receive the standard of care may experience benefits associated with strict adherence to treatment schedules, dosing, and supportive care required by study protocols. A singleinstitution study demonstrated that children with cancer treated in clinical trials showed a trend toward improved outcomes.[5] We hypothesized that children with neuroblastoma would experience benefits associated with clinical trial enrollment. Throughout the world, treatment of neuroblastoma is tailored according to the risk of relapse and death based on a combination of clinical and genetic prognostic biomarkers.[6] In the Children’s Oncology Group (COG), patients with low-risk disease have excellent outcomes, and current studies are evaluating whether subsets of these children may be cured with observation alone (NCT02176967). A series of COG and legacy North American cooperative groups (Pediatric Oncology Group [POG] and Children’s Cancer Group [CCG]) studies have established that patients with intermediate-risk disease have excellent outcomes with surgery and moderate-dose chemotherapy.[6] Successive studies (POG 9243,7 COG A3961,8 and COG ANBL05319) have demonstrated that therapy reduction approaches effectively maintain excellent outcomes for these patients. Similar results have been observed in European protocols for low-risk and intermediate-risk neuroblastoma.[10,11,12]
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