A national analysis on ALK+ anaplastic large cell lymphomas: Community-based care linked to similar survival outcomes compared to academic centers.

Abstract

Abstract Background: Anaplastic large cell lymphomas (ALCLs) are malignancies of mature T lymphocytes, characterized by CD30 marker expression. Around 60% of ALCL cases harbor the translocation involving the anaplastic lymphoma kinase (ALK) gene, resulting in constitutive activation of the ALK-kinase (Blood PMID: 17519389). ALK+ ALCL often affects young patients (median age: 34 years), with extensive nodal and extranodal involvement at presentation. Despite its aggressive biology, patients respond well to anthracycline-based regimens, with PFS and OS of 64% and 77% at 5 years, respectively (Hematol Oncol PMID: 36083035). This disease is rare, with an overall relative frequency of 1-3% among all the non-Hodgkin lymphomas (Nat Rev Cancer PMID: 32249838). While several retrospective and prospective studies reported the epidemiology, clinical features and outcomes of ALK+ ALCL, there is limited data comparing the outcomes for patients with this disease treated at academic cancer programs (ACPs) versus (vs.) community cancer programs (CCPs). This study utilizes the National Cancer Database (NCDB) to assess the clinical, demographic and survival differences between these facility types. Methods We conducted a retrospective analysis of patients with ALK+ ALCL diagnosed in the United States between 2004 and 2022 using the NCDB. Demographic, clinical and survival data were compared between patients treated at ACPs and CCPs. ACPs included academic and research programs, including NCI-designated comprehensive cancer centers. CCPs comprised community, comprehensive community, and integrated network cancer programs. Kaplan-Meier and Cox proportional hazards models were used to compare overall survival (OS), adjusting for age, race/ethnicity, insurance status, comorbidity score (Charlson-Deyo), and distance from treating facility. Results A total of 9,197 patients with ALK+ALCL were identified, with 4172 (45%) treated at ACPs, and 3058 (33%) treated at CCPs. Facility type was unavailable for 1967 (21%) of patients. ALK+ ALCL affected mostly men (60%) and white patients (79%). ACPs saw a greater proportion of patients under 60 years of age (45% vs. 37%) and with advanced disease (stage III/IV, 49% vs. 45%). Insurance coverage differed significantly, with CCPs taking care of more Medicare-insured patients (50% vs. 41%), whereas ACPs saw more patients with private insurance (43% vs. 38%, p<0.001). ACPs saw slightly more patients with Medicaid insurance (8.4% vs. 6.2%). Both facilities saw similar numbers of uninsured patients (3.8% in ACPs and 3.5% in CCPs). Comparison of the great circle distance (CROWFLY), a variable measuring the distance between a patient's residence and treatment facility, revealed patients at ACPs resided further from the treatment center (11.4 miles vs. 8.3 miles, p<0.001). Regarding treatment approaches, treatment initiation rates were higher in ACPs compared to CCPs (61% vs 54%). Both facility types had the same median time-to-chemotherapy initiation of 24 days. However, CCPs performed slightly more radiation compared to ACPs (19% vs. 16%, p<0.001). Kaplan-Meier-estimated OS at 2, 5 and 10 years at APCs were 51%, 35% and 24% respectively and 46%, 33% and 38% for CCPs. The median adjusted survival time was 4.78 years for patients at ACPs and 4.99 years for patients at CCPs. In a multivariable Cox model adjusting for age, race/ethnicity, insurance status, distance to care and comorbidity score— receiving care at a ACPs did not lead to overall improved outcomes compared to CCPs (p=0.815). Conclusion This nationwide study encompassed a large cohort of over 9,000 patients with ALK+ ALCL treated within both academic cancer programs (ACPs) and community cancer programs (CCPs). Despite ACPs managing a higher proportion of patients with advanced-stage disease at diagnosis, overall survival did not differ between the two healthcare settings. This may, in part, reflect demographic differences, as patients treated in ACPs tended to be younger, and therefore more likely to tolerate and complete aggressive therapy. It could also be explained by the disease's favorable prognosis, usually responsive to modern frontline regimens, which likely contributes to high survival rates observed across both healthcare settings. Collectively, these findings highlight the respective strengths of ACPs and CPPs and reinforce the value of community-based oncology in delivering effective cancer care.