Nutritional risk and cancer pain as determinants of radiotherapy-induced severe lymphocytopenia: development and validation of a nutrition-integrated predictive nomogram

Background Radiotherapy-induced severe lymphocytopenia (SL) represents a critical immune-related toxicity associated with poor oncologic outcomes. While treatment-related factors have been extensively studied, the contribution of baseline nutritional risk and cancer-related pain to immune vulnerability during radiotherapy remains insufficiently explored. This study aimed to evaluate the role of nutrition- and symptom-related factors in SL and develop a clinically applicable predictive model. Methods A retrospective cohort of 97 cancer patients receiving radiotherapy in 2022 was analyzed. Nutritional risk was assessed using the Nutritional Risk Screening 2002 (NRS-2002) before radiotherapy and at mid-treatment; the pretreatment result was used as the baseline nutritional risk variable in the predictive analyses, whereas the mid-treatment assessment was used for nutritional monitoring. Cancer pain was evaluated using the Numeric Rating Scale. Logistic regression identified independent predictors of SL (lymphocyte count < 0.5 × 10 9 /L). A nutrition-integrated nomogram was developed and internally validated using ROC analysis, calibration curves, and decision curve analysis (DCA). Results Lymphocyte counts declined progressively during radiotherapy ( p < 0.001), with 42.3% of patients developing SL. Multivariable analysis identified nutritional risk (OR = 3.53, p = 0.016), cancer pain (OR = 3.78, p = 0.037), and radiotherapy fractions (OR = 1.11 per fraction, p = 0.006) as independent predictors. Stratified analysis suggested a stronger association between cancer pain and SL among nutritionally at-risk patients. The nomogram demonstrated good discrimination (AUC = 0.77; C-index = 0.77), adequate calibration (Hosmer–Lemeshow p = 0.45), and meaningful clinical net benefit across a threshold range of 0.18–0.90. Conclusion Nutritional risk and cancer pain independently contribute to radiotherapy-induced immune suppression. The proposed nutrition-integrated nomogram enables personalized immune risk assessment and supports early nutritional and symptom-targeted interventions to preserve immune competence during radiotherapy.