REAL-WORLD EVIDENCE CHALLENGING THE THERAPY-DEPENDENT RISK PARADIGM FOR THERAPY-RELATED AML IN HEAD AND NECK CANCER SURVIVORS
Author(s)
Ahmed Elkoumi, BDS1, Omar Elkoumi, MBBCh2;
1Health Affairs Directorate of Elsharqeya, Ministry of Health and Population, Elsharqeya, Egypt, 2Faculty of Medicine, Suez, Egypt
1Health Affairs Directorate of Elsharqeya, Ministry of Health and Population, Elsharqeya, Egypt, 2Faculty of Medicine, Suez, Egypt
OBJECTIVES: Clinical guidelines for monitoring secondary malignancies often prioritize patients with high cumulative exposure to cytotoxic therapy. However, the real-world validity of using therapeutic intensity as a proxy for risk in head and neck squamous cell carcinoma (HNSCC) survivors is unclear. We aimed to evaluate the predictive value of demographic versus treatment-related factors in the development of therapy-related acute myeloid leukemia (t-AML) to inform more efficient, risk-stratified survivorship strategies.
METHODS: We conducted a retrospective, population-based cohort study utilizing the SEER database (2000-2022) to analyze outcomes in 126,653 HNSCC survivors. To overcome survivorship bias and account for non-cancer mortality, we employed Fine-Gray competing risks regression. We assessed the independent prognostic impact of age (<60 vs. ≥60 years), sex, and tumor sub-site relative to therapeutic modalities (chemotherapy and radiation), to isolate specific drivers of t-AML burden.
RESULTS: A treatment paradox was evident between younger (<60 years) and older (≥60 years) cohorts. Younger patients more often received intensive therapy, with chemotherapy in 49% and radiation in 66%, compared with 37% and 57% among older patients, respectively (p<0.001). Despite lower treatment exposure, older patients had a significantly higher cumulative incidence of AML (p<0.001). In competing risks models, age ≥60 years (HR: 2.02, p<0.001), male sex (HR: 1.95, p=0.003), and chemotherapy exposure (HR: 1.55, p=0.035) were independently associated with AML risk. In contrast, radiation therapy was not associated with increased risk (HR: 0.58, p=0.007).
CONCLUSIONS: The amount of treatment a patient receives is not the main driver of secondary AML. Instead, biological factors like age and sex matter much more. Current guidelines that focus on monitoring "heavily treated" patients are inefficient because they overlook the highest-risk group: older men who received standard or even lighter treatments. Surveillance strategies need to change to focus on patient frailty rather than just cumulative dose.
METHODS: We conducted a retrospective, population-based cohort study utilizing the SEER database (2000-2022) to analyze outcomes in 126,653 HNSCC survivors. To overcome survivorship bias and account for non-cancer mortality, we employed Fine-Gray competing risks regression. We assessed the independent prognostic impact of age (<60 vs. ≥60 years), sex, and tumor sub-site relative to therapeutic modalities (chemotherapy and radiation), to isolate specific drivers of t-AML burden.
RESULTS: A treatment paradox was evident between younger (<60 years) and older (≥60 years) cohorts. Younger patients more often received intensive therapy, with chemotherapy in 49% and radiation in 66%, compared with 37% and 57% among older patients, respectively (p<0.001). Despite lower treatment exposure, older patients had a significantly higher cumulative incidence of AML (p<0.001). In competing risks models, age ≥60 years (HR: 2.02, p<0.001), male sex (HR: 1.95, p=0.003), and chemotherapy exposure (HR: 1.55, p=0.035) were independently associated with AML risk. In contrast, radiation therapy was not associated with increased risk (HR: 0.58, p=0.007).
CONCLUSIONS: The amount of treatment a patient receives is not the main driver of secondary AML. Instead, biological factors like age and sex matter much more. Current guidelines that focus on monitoring "heavily treated" patients are inefficient because they overlook the highest-risk group: older men who received standard or even lighter treatments. Surveillance strategies need to change to focus on patient frailty rather than just cumulative dose.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
EPH203
Topic
Epidemiology & Public Health
Disease
SDC: Oncology