Clinical Considerations of Splenic Dose Constraints to Mitigate Radiation-Induced Lymphopenia

The spleen dose-volume threshold for lymphopenia in abdominal radiotherapy has not yet reached a consensus. Our previous research indicated a correlation between these factors, but the threshold has not been determined. Therefore, we investigated the dynamic changes in lymphocytes during radiotherapy (RT), identified the spleen dose threshold, and examined how these factors affect patient prognosis.

The absolute lymphocyte counts (ALC) of gastric cancer patients were collected before, during, and after RT. Lymphocyte recovery status was assessed using the lymphocyte recovery index (LRI). LRI cut off was considered as insufficient recovery. Splenic dosimetric parameters were collected, and their impact on predicting grade 4 (G4) lymphopenia was evaluated using logistic regression analysis. Cox regression analysis was used to evaluate the relationship between lymphocyte depletion and recovery status and prognosis.

159 patients were enrolled. The median ALC dropped by 85.71% after RT. The occurrence of G4 and G1-3 lymphopenia was observed in 30.2% and 69.8% of cases, respectively. There were 12.6% of patients whose ALC had recovered at 120 days after RT, while the remaining 87.4% were still accompanied by lymphopenia. Cox multivariable analysis showed that pTNM stage and LRI were independent prognostic factors affecting overall survival, and the independent prognostic factors for disease-free survival were pTNM stage and change in ALC. Splenic D_mean and V₅ were related to G4 lymphopenia and eventually V₅ affected prognosis. Constraining the spleen V₅ to < 180.6 cm³ and < 272.2 cm³ may reduce the incidence of G4 lymphopenia and further decrease the risk of death by 60.9%.

Patients with severe lymphocyte decline during RT and insufficient lymphocyte recovery afterward have a worse prognosis. It is important not only to prevent severe lymphopenia during RT but also to focus on improving lymphocyte recovery after RT. Constraining the spleen V₅ is a key approach.