Adolescents and young adult acute myeloid leukemia outcomes at pediatric versus adult centers: A population-based study.

Adolescents and young adult (AYA) acute myeloid leukemia (AML) outcomes remain poor. The impact of locus of care (LOC; adult vs pediatric) in this population is unknown. The IMPACT cohort comprises detailed data for all Ontario, Canada, AYA aged 15-21 years diagnosed with AML between 1992 and 2012, linked to population-based health administrative data. We determined the impact of LOC on event-free survival (EFS) and overall survival (OS), treatment-related mortality (TRM), and relapse/progression. Among 140 AYA, 51 (36.4%) received therapy at pediatric centers. The five-year EFS and OS for the whole cohort were 35.0% ± 4.0% and 53.6% ± 4.2%. Cumulative doses of anthracycline were higher among pediatric center AYA [median 355 mg/m2 , interquartile range (IQR) 135-492 vs 202 mg/m2 , IQR 140-364; P = 0.003]. In multivariable analyses, LOC was not predictive of either EFS [adult vs pediatric center hazard ratio (HR) 1.3, 95% confidence interval (CI) 0.8-2.2, P = 0.27] or OS (HR 1.0, CI 0.6-1.6, P = 0.97). However, patterns of treatment failure varied; higher two-year incidence of TRM in pediatric centers (23.5% ± 6.0% vs.10.1% ± 3.2%; P = 0.046) was balanced by lower five-year incidence of relapse/progression (33.3% ± 6.7% vs 56.2% ± 5.3%; P = 0.002). AYA AML survival outcomes did not vary between pediatric and adult settings. Causes of treatment failure were different, with higher intensity pediatric protocols associated with higher TRM but lower relapse/progression. Careful risk stratification and enhanced supportive care may be of substantial benefit to AYA with AML by allocating maximal treatment intensity to patients who most benefit while minimizing the risk of TRM.

Gupta S ，Baxter NN ，Sutradhar R ，Pole JD ，Nagamuthu C ，Lau C ，Nathan PC ... -  《-》

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

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.

Gupta S ，Baxter NN ，Hodgson D ，Punnett A ，Sutradhar R ，Pole JD ，Nagamuthu C ，Lau C ，Nathan PC ... -  《Cancer Medicine》

The effect of adopting pediatric protocols in adolescents and young adults with acute lymphoblastic leukemia in pediatric vs adult centers: An IMPACT Cohort study.

Retrospective 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. The 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. Of 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. Survival 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.

Gupta S ，Pole JD ，Baxter NN ，Sutradhar R ，Lau C ，Nagamuthu C ，Nathan PC ... -  《Cancer Medicine》

Impact of locus of care on outcomes in adolescents and young adults with osteosarcoma and Ewing sarcoma treated at pediatric versus adult cancer centers: An IMPACT cohort study.

Location of cancer care (LOC; pediatric vs. adult center) impacts outcomes in adolescents and young adults (AYA) with some cancer types. Data on the impact of LOC on survival in AYA with osteosarcoma (OSS) and Ewing sarcoma (EWS) are limited OBJECTIVES: To compare differences in demographics, disease/treatment characteristics, and survival in a population-based cohort of AYA with OSS or EWS treated at pediatric versus adult centers METHODS: The Initiative to Maximize Progress in Adolescent Cancer Therapy (IMPACT) cohort captured demographic, disease, and treatment data for all AYA (15-21 years old) diagnosed with OSS and EWS in Ontario, Canada between 1992 and 2012. Patients were linked to provincial administrative health care databases. Outcomes were compared between patients treated in pediatric versus adult centers. One hundred thirty-seven AYA were diagnosed with OSS (LOC: 47 pediatric, 90 adult) and 84 with EWS (38 pediatric, 46 adult). AYA treated at pediatric centers were more likely to be enrolled in a clinical trial (OSS 55% vs. 1%, p < .001; EWS 53% vs. 2%, p < .001) and received higher cumulative chemotherapy doses. Five-year event-free survival (EFS ± standard error) in OSS and EWS were 47% ± 4% and 43% ± 5%, respectively. In multivariable analysis, the impact of LOC (pediatric vs. adult center) on EFS in OSS (adjusted hazard ratio [HR] 1.15, 95% confidence interval [CI]: 0.58-2.27, p = .69) and EWS (adjusted HR 1.82, 95% CI: 0.97-3.43, p = .06) was not statistically significant. Despite disparities in trial participation and chemotherapy doses, outcomes did not differ by LOC suggesting that AYA with bone tumors can be treated at either pediatric or adult centers.

Mortazavi M ，Baxter NN ，Gupta S ，Gupta AA ，Lau C ，Nagamuthu C ，Nathan PC ... -  《-》

Superior outcomes with paediatric protocols in adolescents and young adults with aggressive B-cell non-Hodgkin lymphoma.

Survival disparities by locus of care (LOC; paediatric versus adult) among adolescents and young adults (AYA) with acute lymphoblastic leukaemia (ALL) are well documented. Whether similar disparities exist among AYA with aggressive mature B-cell non-Hodgkin lymphoma (B-NHL) is unknown. We identified all Ontario, Canada AYA aged 15-21 years at diagnosis of B-NHL between 1992 and 2012. Demographic, disease, treatment and outcome data were chart abstracted. The impact of LOC on event-free (EFS) and overall survival (OS) were determined, adjusted for patient and disease covariates. Among 176 AYA with B-NHL, 62 (35·2%) received therapy at paediatric centres. The 5-year EFS and OS [± standard error (SE)] for the overall cohort were 72·2 [3·4]% and 76·1 [3·2]% respectively. Both EFS and OS were superior among paediatric centre AYA [EFS (± SE) 82·2 (4·9)% vs. 66·7 (4·4)%, P = 0·02; OS 85·5 (4·5)% vs. 71·1 (4·3)%, P = 0·03]. Adjusted for histology, stage and time period, adult centre AYA had inferior EFS [hazard ratio (HR) 2·4, 95% confidence interval (CI) 1·1-4·9, P = 0·02] and OS (HR 2·5, 95% CI 1·1-5·7, P = 0·03). Sensitivity analyses restricted to the latest time period, when most adult centre AYA received rituximab, demonstrated similar disparities. Similar to AYA with ALL, AYA with B-NHL may benefit from being treated with paediatric protocols. Studies prospectively validating these results are warranted.

Gupta S ，Alexander S ，Pole JD ，Sutradhar R ，Crump M ，Nagamuthu C ，Baxter NN ，Nathan PC ... -  《-》