Spleen Dose–Volume Parameters as a Predictor of Treatment-related Lymphopenia During Definitive Chemoradiotherapy for Esophageal Cancer

Abstract

Aim: Our study sought to identify dosimetric predictors of treatment-related lymphopenia during chemoradiotherapy for esophageal cancer. Materials and Methods: Patients with esophageal cancer who had received definitive chemoradiotherapy at our Institution were retrospectively assessed. The absolute volume of the spleen, body, and bone marrow that had received 5, 10, 20, and 30 Gy and the mean splenic dose were recorded. Results: Multivariate linear regression analysis revealed that docetaxel use and spleen dose-volume parameters (V5, V10, V20, V30, and mean splenic dose) were significant independent factors negatively influencing the absolute lymphocyte count at nadir. An increase of 1 Gy in mean splenic dose predicted a 2.9% decrease in nadir absolute lymphocyte count. Univariable logistic regression analysis showed that the mean splenic dose was a significant predictor of grade 4 lymphopenia. None of the body or bone marrow dose-volume parameters significantly predicted lymphopenia. Conclusion: Higher spleen dose-volume parameters were associated with severe lymphopenia during chemoradiotherapy. The important role of lymphocytes in the immune response to cancer is evidenced by reports that show better survival of patients with lung, colorectal, and breast cancer who have lymphocyte infiltration in the tumor tissue (1-3). Recent studies demonstrated that treatment-related lymphopenia was associated with poor outcome in patients undergoing definitive chemoradiotherapy (CRT) for esophageal, pancreatic, lung, cervical, and nasopharyngeal cancer (4-8). Lymphocytes are highly radiosensitive, and exposure to low doses of radiation can lead to a decrease in the number of peripheral blood lymphocytes (9). Radiation-related lymphopenia can thus affect the immune system and the treatment outcome. Previous studies have suggested that radiation-related lymphopenia is associated with the irradiation of lymphoid tissue including the spleen (10) and bone marrow (11), or the irradiation of peripheral blood lymphocytes (12,13). However, in CRT for esophageal cancer, mechanisms of treatment-related lymphopenia have not been clarified. Therefore, focusing on dose-volume parameters, we sought to identify predictors of lymphopenia during CRT for esophageal cancer. Materials and Methods Patients. This retrospective study was approved by the Institutional Review Board of our hospital (approval number, 1533). Patient informed consent was waived due to the retrospective nature of the study. The study was carried out according to the Declaration of Helsinki. Our inclusion criteria were as follows: Patients who completed definitive CRT for esophageal cancer between January 2011 and August 2015 and whose chemotherapy regimen included cisplatin. The exclusion criteria were: Previous radiotherapy (RT); chemotherapy performed before CRT; and CRT performed as preoperative treatment. Laboratory data. The study endpoints were as follows: (i) the absolute lymphocyte count (ALC) at nadir, defined as the lowest value recorded during CRT; and (ii) ...

Low Lymphocyte Count Is Associated With Radiotherapy Parameters and Affects the Outcomes of Esophageal Squamous Cell Carcinoma Patients

“…Nevertheless, the mechanisms responsible for RIL remain unclear. Lymphoid organ radiation, including bone marrow, thymus, spleen, and lymph nodes, could likely contribute to RIL (22)(23)(24). Radiation can directly damage hematopoietic stem cells in bone marrow or mature lymphocytes in lymphoid tissues, as well as stimulate the secretion of immunosuppressive cytokines, promoting immunosuppression (25).…”

Ultra high dose rate (35 Gy/sec) radiation does not spare the normal tissue in cardiac and splenic models of lymphopenia and gastrointestinal syndrome

“…Whereas most studies demonstrate RIL as a poor prognostic factor in cancer treatment outcomes, the direct correlation between dose to lymphocyte-rich organs and RIL has been most recently described in pancreatic cancer patients receiving unintentional splenic RT and esophageal cancer patients receiving unintentional cardiac and splenic RT 10,17,18 . Using irradiation of these two lymphocyte-rich organs as our model system for RIL, we studied the potential normal tissue sparing ability of ultra-high dose rate RT.…”

Lymphopenia and Radiation Dose to Circulating Lymphocytes With Neoadjuvant Chemoradiation in Esophageal Squamous Cell Carcinoma

“…As both lung cancers and esophageal cancers are mainly located within the thoracic region, we believe that the EDIC formula would be a valid model in esophageal cancer too. On the other hand, Saito et al 22 found that splenic dose volumes but not bone marrow dose volumes were predictive in treatment-related lymphopenia during chemoradiotherapy for esophageal cancer. We believe future studies can incorporate dose to the spleen as a better estimate of dose to EDIC.…”