The impact of chemotherapy relative dose intensity on survival in elderly patients with extranodal NK/T-cell lymphoma: A retrospective cohort study.

BACKGROUND: Optimizing chemotherapy for elderly patients with extranodal natural killer/T-cell lymphoma (ENKTL) represents a significant clinical challenge, requiring a balance between effective relative dose intensity (RDI) and treatment tolerance. The prognostic impact of RDI in this population remains unclear. OBJECTIVES: To investigate the relationship between RDI and survival outcomes and to establish a clinically meaningful RDI threshold for elderly ENKTL patients. DESIGN: A retrospective observational single-center cohort study. METHODS: The study analyzed treatment-naïve ENKTL patients aged ≥60 years who received DDGP-like regimens or P-GEMOX regimen between May 2016 and December 2023. The optimal RDI cutoff was determined by receiver operating characteristic curve analysis. Variable selection for multivariable Cox regression was performed using least absolute shrinkage and selection operator (LASSO) regression to mitigate overfitting and adjust for potential confounders. The primary endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 79 patients were enrolled. The median number of chemotherapy cycles was 3 (IQR: 3-5), with a median treatment interval of 26 days (IQR: 23-31). Treatment delays exceeding one week occurred in 55.7% of patients (n = 44), and only 2.5% (n = 2) received full dose intensity (RDI = 1). An average RDI ≥ 0.62 was significantly associated with prolonged PFS (p = 0.010) and OS (p = 0.012). Multivariable analysis confirmed higher RDI as an independent predictor of superior PFS (HR = 0.385, 95% CI: 0.186-0.801, p = 0.011) and OS (HR = 0.433, 95% CI: 0.194-0.968, p = 0.041). Furthermore, age≥70 years (vs.60-70 years; p = 0.007), diabetes (p = 0.039), and adverse events including infection (p = 0.033), rash (p = 0.043), and diarrhea (p = 0.017) were significant predictors of reduced RDI. CONCLUSION: An ARDI ≥ 0.62 may represent a critical threshold associated with improved prognosis in elderly ENKTL. However, this observation is preliminary and warrants further validation in prospective studies.