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Treatment patterns and outcomes in adolescents and young adults with Hodgkin lymphoma in pediatric versus adult centers: An IMPACT Cohort Study.

ABSTRACT: Hodgkin lymphoma (HL) is a common adolescent and young adult (AYA) cancer. While outcome disparities between pediatric vs. adult centers [locus of care (LOC)] have been demonstrated in other AYA cancers such as acute lymphoblastic leukemia, they have not been well studied in HL. We therefore compared population-based treatment patterns and outcomes in AYA HL by LOC. The IMPACT Cohort includes data on all Ontario, Canada AYA (15-21 years) diagnosed with HL between 1992 and 2012. Linkage to population-based health administrative data identified late effects. We examined LOC-based differences in treatment modalities, cumulative doses, event-free survival (EFS), overall survival (OS), and late effects. Among 954 AYA, 711 (74.5%) received therapy at adult centers. Pediatric center AYA experienced higher rates of radiation therapy but lower cumulative doses of doxorubicin and bleomycin. 10-year EFS did not differ between pediatric vs. adult cancer vs. community centers (83.8% ± 2.4% vs. 82.8% ± 1.6% vs. 82.7%±3.0%; P = .71); LOC was not significantly associated with either EFS or OS in multivariable analyses. Higher incidences of second malignancies in pediatric center AYA and of cardiovascular events in adult center AYA were observed, but were not significant. In conclusion, while pediatric and adult centers used different treatment strategies, outcomes were equivalent. Differences in treatment exposures are however likely to result in different late-effect risks. Protocol choice should be guided by individual late-effect risk.

SUBMITTER: Gupta S

PROVIDER: S-EPMC7541154 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Treatment patterns and outcomes in adolescents and young adults with Hodgkin lymphoma in pediatric versus adult centers: An IMPACT Cohort Study.

Gupta Sumit S Baxter Nancy N NN Hodgson David D Punnett Angela A Sutradhar Rinku R Pole Jason D JD Nagamuthu Chenthila C Lau Cindy C Nathan Paul C PC

Cancer medicine 20200522 19

Hodgkin lymphoma (HL) is a common adolescent and young adult (AYA) cancer. While outcome disparities between pediatric vs. adult centers [locus of care (LOC)] have been demonstrated in other AYA cancers such as acute lymphoblastic leukemia, they have not been well studied in HL. We therefore compared population-based treatment patterns and outcomes in AYA HL by LOC. The IMPACT Cohort includes data on all Ontario, Canada AYA (15-21 years) diagnosed with HL between 1992 and 2012. Linkage to popula ...[more]

PMID: 32441450

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Project description:BackgroundRetrospective studies have shown adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) have superior survival when treated in pediatric versus adult centers (locus of care; LOC). Several adult centers recently adopted pediatric protocols. Whether this has narrowed LOC disparities in real-world settings is unknown.MethodsThe IMPACT Cohort is an Ontario population-based cohort that captured demographic, disease and treatment (treatment protocol, chemotherapy doses) data for all 15-21 year olds diagnosed with ALL 1992-2011. Cancer outcomes were determined by chart abstraction and linkage to provincial healthcare databases. Treatment protocols were classified as pediatric- or adult-based. We examined predictors of outcome, including LOC, protocol, disease biology, and time period.ResultsOf 271 patients, 152 (56%) received therapy at adult centers. 5-year event-free survival (EFS ± SE) among AYA at pediatric vs adult centers was 72% ± 4% vs 56% ± 4% (P = 0.03); 5-year overall survival (OS) was 82% ± 4% vs 64% ± 4% (P < 0.001). After adjustment, OS remained inferior at adult centers (hazard ratio 2.5; 95% confidence interval 1.1-6.1; P = 0.04). In the most recent period (2006-2011), 39/59 (66%) AYA treated at adult centers received pediatric protocols. These AYA had outcomes superior to the 20 AYA treated on adult protocols, but inferior to the 44 AYA treated at pediatric centers (EFS 72% ± 5% vs 60% ± 9% vs 81% ± 6%; P = 0.02; OS 77% ± 7% vs 65% ± 11% vs 91% ± 4%; P = 0.004). Induction deaths and treatment-related mortality did not vary by LOC.ConclusionsSurvival disparities between AYA with ALL treated in pediatric vs adult centers have persisted over time, partially attributable to incomplete adoption of pediatric protocols by adult centers. Although pediatric protocol use has improved survival, residual disparities remain, perhaps due to other differences in care between adult and pediatric centers.

Project description:BackgroundIncreased glycolytic activity is a hallmark of cancer, allowing staging and restaging with 18F-fluorodeoxyglucose-positron-emission-tomography (PET). Since interim-PET is an important prognostic tool in Hodgkin lymphoma (HL), the aim of this study was to investigate the expression of proteins involved in the regulation of glucose metabolism in the different HL subtypes and their impact on clinical outcome.MethodsLymph node biopsies from 54 HL cases and reactive lymphoid tissue were stained for glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA) and lactate exporter proteins MCT1 and MCT4. In a second series, samples from additional 153 HL cases with available clinical data were stained for GLUT1 and LDHA.ResultsMembrane bound GLUT1 expression was frequently observed in the tumor cells of HL (49% of all cases) but showed a broad variety between the different Hodgkin lymphoma subtypes: Nodular sclerosing HL subtype displayed a membrane bound GLUT1 expression in the Hodgkin-and Reed-Sternberg cells in 56% of the cases. However, membrane bound GLUT1 expression was more rarely observed in tumor cells of lymphocyte rich classical HL subtype (30%) or nodular lymphocyte predominant HL subtype (15%). Interestingly, in both of these lymphocyte rich HL subtypes as well as in progressively transformed germinal centers, reactive B cells displayed strong expression of GLUT1. LDHA, acting downstream of glycolysis, was also expressed in 44% of all cases. We evaluated the prognostic value of different GLUT1 and LDHA expression patterns; however, no significant differences in progression free or overall survival were found between patients exhibiting different GLUT1 or LDHA expression patterns. There was no correlation between GLUT1 expression in HRS cells and PET standard uptake values.ConclusionsIn a large number of cases, HRS cells in classical HL express high levels of GLUT1 and LDHA indicating glycolytic activity in the tumor cells. Although interim-PET is an important prognostic tool, a predictive value of GLUT1 or LDHA staining of the primary diagnostic biopsy could not be demonstrated. However, we observed GLUT1 expression in progressively transformed germinal centers and hyperplastic follicles, explaining false positive results in PET. Therefore, PET findings suggestive of HL relapse should always be confirmed by histology.

Dataset Information

Treatment patterns and outcomes in adolescents and young adults with Hodgkin lymphoma in pediatric versus adult centers: An IMPACT Cohort Study.

Publications

Treatment patterns and outcomes in adolescents and young adults with Hodgkin lymphoma in pediatric versus adult centers: An IMPACT Cohort Study.

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