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Original Investigation
January 3, 2019

Association of Combined Modality Therapy vs Chemotherapy Alone With Overall Survival in Early-Stage Pediatric Hodgkin Lymphoma

Author Affiliations
  • 1Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick
  • 2Biometrics Division, Rutgers Cancer Institute of New Jersey, New Brunswick
  • 3Department of Biostatistics, Rutgers School of Public Health, New Brunswick, New Jersey
  • 4Section of Pediatric Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick
  • 5Department of Radiation Oncology, University of Florida, Gainesville
  • 6University of Florida Health Proton Therapy Institute, Jacksonville
JAMA Oncol. Published online January 3, 2019. doi:10.1001/jamaoncol.2018.5911
Key Points

Question  Is there a survival benefit to combined modality therapy with chemotherapy and radiotherapy vs chemotherapy alone in pediatric Hodgkin lymphoma?

Findings  In this cohort study of 5657 pediatric patients from the National Cancer Database, combined modality therapy was associated with an improved overall survival of 2.8% compared with chemotherapy alone at 5 years, with a particular benefit seen in the low-risk cohort and young adult patients. The use of combined modality therapy has been decreasing in the United States.

Meaning  Combined modality therapy may be discussed with pediatric patients with Hodgkin lymphoma, and future clinical trials may consider including combined modality therapy as a standard arm.

Abstract

Importance  To date, there is no well-defined standard of care for early-stage pediatric Hodgkin lymphoma (HL), which may include chemotherapy alone or combined modality therapy (CMT) with chemotherapy followed by radiotherapy. Although the use of radiotherapy in pediatric HL is decreasing, this strategy remains controversial.

Objective  To examine the use of CMT in pediatric HL and its association with improved overall survival using data from a large cancer registry.

Design, Setting, and Participants  This observational cohort study used data from the National Cancer Database to evaluate clinical features and survival outcomes among 5657 pediatric patients (age, 0.1-21 years) who received a diagnosis of stage I or II HL in the United States from January 1, 2004, to December 31, 2015. Statistical analysis was conducted from May 1 to November 1, 2018.

Exposures  Patients received definitive treatment with chemotherapy or CMT, defined as chemotherapy followed by radiotherapy.

Main Outcomes and Measures  Kaplan-Meier survival curves were used to examine overall survival. The association between CMT use, covariables, and overall survival was assessed in multivariable Cox proportional hazards regression models. Use of radiotherapy was assessed over time.

Results  Among the 11 546 pediatric patients with HL in the National Cancer Database, 5657 patients (3004 females, 2596 males, and 57 missing information on sex; mean [SD] age, 17.1 [3.6] years) with stage I or II classic HL were analyzed. Of these patients, 2845 (50.3%) received CMT; use of CMT vs chemotherapy alone was associated with younger age (<16 years, 1102 of 2845 [38.7%] vs 856 of 2812 [30.4%]; P < .001), male sex (1369 of 2845 [48.1%] vs 1227 of 2812 [43.6%]; P < .001), stage II disease (2467 of 2845 [86.7%] vs 2376 of 2812 [84.5%]; P = .02), and private health insurance (2065 of 2845 [72.6%] vs 1949 of 2812 [69.3%]; P = .002). The 5-year overall survival was 94.5% (confidence limits, 93.8%, 95.8%) for patients who received chemotherapy alone and 97.3% (confidence limits, 96.4%, 97.9%) for those who received CMT, which remained significant in the intention-to-treat analysis and multivariate analysis (adjusted hazard ratio for CMT, 0.57; 95% CI, 0.42-0.78; P < .001). In the sensitivity analysis, the low-risk cohort (stage I-IIA) and adolescent and young adult patients had the greatest benefit from CMT (adjusted hazard ratio, 0.47; 95% CI, 0.40-0.56; P < .001). The use of CMT decreased by 24.8% from 2004 to 2015 (from 59.7% [271 of 454] to 34.9% [153 of 438]).

Conclusions and Relevance  In this study, pediatric patients with early-stage HL receiving CMT experienced improved overall survival 5 years after treatment. There is a nationwide decrease in the use of CMT, perhaps reflecting the bias of ongoing clinical trials designed to avoid consolidation radiotherapy. This study represents the largest data set to date examining the role of CMT in pediatric HL.

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