Predictors of Severe Lymphopenia During Chemoradiation Therapy for Anal Cancer

Abstract

Purpose/Objective(s): Lymphopenia has been associated with poorer outcomes in multiple solid malignancies, including anal squamous cell carcinoma (ASCC). Lymphopenia is particularly important in the setting of chemoradiation (CRT) for ASCC given the trials underway to evaluate the potential role of immunotherapy in localized anal cancer. This study looks to identify clinical, tumor, and dosimetric factors that predict for severe lymphopenia during CRT for ASCC. Materials/Methods: Patients diagnosed with anal canal or anal margin squamous cell carcinoma from 2016-2019 and treated with CRT at our Cancer Institute/Department of Radiation Oncology were identified. Only patients who received 5-fluorouracil and mitomycin C (5FU/MMC) chemotherapy with concurrent intensity modulated radiation therapy (IMRT) to 50.4-59.4 Gy with definitive intent were included in this analysis. Charts and lab results were reviewed and absolute lymphocyte count (ALC) nadir during CRT was recorded. Those with ALC nadir < 0.2 x 109/L were identified as having Grade 4 lymphopenia. Multivariable logistic regression analysis was used to develop a prediction model for Grade 4 lymphopenia. Factors analyzed included age, gender, BMI, HIV status, history of prior malignancy, pretreatment ALC, T-stage, nodal status, group stage, PTVa volume, PTV total volume, radiation prescription dose, volume of iliac crest receiving 30 Gy (iliac crest V30), 40 Gy, (V40), and 50 Gy (V50), and overall radiation plan hotspot. A total of 51 patients treated with definitive 5FU/MMC and IMRT were identified. The mean age was 61 years. Forty-three (84%) were women and 8 (16%) were men. The median BMI was 27. Three patients had a known diagnosis of HIV and 3 had a history of prior malignancy. Fourteen percent of patients had Stage I, 31% had Stage II, 53% had Stage III, and 2% had oligometastatic stage IV disease. Median prescribed radiation dose was 54 Gy. Thirty patients (59%) developed Grade 4 lymphopenia during the course of CRT. On univariable logistic regression, T-stage, nodal status, PTVa volume, PTV total volume, radiation prescription dose, iliac crest V40, iliac crest V50, and radiation plan hotspot were associated with Grade 4 lymphopenia. On multivariable logistic regression iliac crest V40 (p = 0.03) predicted for Grade 4 lymphopenia with an odds ratio of 1.7. The mean iliac crest V40 was 11%. Dose to the iliac crests is an independent predictor for severe lymphopenia during definitive CRT for anal cancer. The use of predictors to identify patients at risk for severe lymphopenia will be increasingly important as interest in immunotherapy in the treatment of ASCC expands.