Severe radiation-induced lymphopenia during postoperative radiotherapy or chemoradiotherapy has poor prognosis in patients with stage IIB-III after radical esophagectomy: A post hoc analysis of a randomized controlled trial

Abstract

ObjectiveTo investigate whether radiation-induced lymphopenia (RIL) affects survival and identify the predictors of RIL in postoperative esophageal cancer.Materials and methodsPost hoc analysis was conducted on data from 116 patients with esophageal cancer from a randomized controlled trial comparing adjuvant therapy with surgery alone. Doses of 54 Gy in 27 fractions was delivered in the postoperative radiotherapy (PORT) group and 50.4 Gy in 28 fractions combined with chemotherapy was delivered in postoperative concurrent chemoradiotherapy (POCRT) group. Blood counts were obtained before, during, and at first follow-up after treatment. Lymphopenia was graded per version 4.03 of the Common Terminology Criteria for Adverse Events. Disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method, and compared between groups using the log-rank test. Receiver operating characteristic curves identified thresholds for preventing grade 4 (G4) lymphopenia.ResultsMedian follow-up duration was 56.0 months. During treatment, 16 patients (13.8%) had G4 lymphopenia. All cases of G4 lymphopenia occurred in group PORT (30.2% vs 0.0%, p<0.001). Baseline absolute lymphocyte count was comparable between G1-3 and G4 patients (2.0 ± 0.8 *109/L vs 1.7 ± 0.5 *109/L; p=0.101). The 3-year DFS was significantly lower in group G4 lymphopenia than that in group G1-3 (31.3% vs 57.6%, p=0.036). The 3-year OS was comparable between both groups (50.0% vs 66.5%, p=0.095). Logistic regression analysis revealed that exposed more thoracic marrow (TM V20 ≥75%; TVB V20 ≥71%), heart (V15 ≥40%) and PTV (volume ≥507 ml) were associated with G4 lymphopenia (p<0.05).ConclusionsG4 RIL had poor disease-free survival, which may be related to more dose exposure of thoracic marrow and heart due to larger PTV. Reasonably reducing the radiation field combined with concurrent chemotherapy, or radiation dose constraints for these normal tissues may be sufficient to decrease the incidence of G4 lymphopenia, but further prospective trials are needed to verify the results.Clinical Trial Registrationclinicaltrials.gov, identifier NCT02279134

Radiation-Induced Lymphopoenia and Treatment Outcome in Hereditary Breast Cancer Patients

“…However, there was a trend toward longer 5y DFS in patients with more severe lymphopoenia compared to patients with no or only mild lymphopoenia observed in the whole group of PV carriers. These observations contrast with previously published reports showing a clear negative effect of RILs on survival parameters in several types of solid tumours, including breast cancer (Venkatesulu et al, 2018;Abravan et al, 2020;Sun et al, 2020;Xie et al, 2020;Ni et al, 2022). Chemotherapy, lung doses, and radiotherapy techniques are reported to be the most important risk factors for the development of RIL in breast cancer after adjuvant radiotherapy (Chen et al, 2021).…”

“…The association between reduced baseline immunity or low lymphocyte counts with cancer prognosis and outcome has been described in several studies (Venkatesulu et al, 2018;Abravan et al, 2020;Xie et al, 2020;Damen et al, 2021;Ni et al, 2022) demonstrating that severe radiotherapy-induced lymphopoenia (RIL; G3 and G4) significantly affects survival parameters in many solid tumours (e.g., oesophageal cancers, pancreatic cancers, and lung tumours) and represents an important prognostic factor. Sun and colleagues (2020) demonstrated a significantly lower 5y DFS for BC patients with more severe RIL (71.8 % vs 82.6 %; P = 0.01) and a lower RIL rate for the patients irradiated with hypofractionated adjuvant chest wall radiotherapy compared with normofractionated radiotherapy.…”

Immune modulatory roles of radioimmunotherapy: biological principles and clinical prospects

“…Lymphopenia is one of the most common adverse events during and after RT in a daily basis, and is deemed to be associated with poorer survival prognosis for cancer patients ( 69 , 70 ). Given that hematopoietic stem cells are sensitive to ionizing radiation, even low-dose irradiation may cause temporary bone marrow dysfunction, while high-dose RT may result in irreversible damage to bone marrow hematopoietic function and mesenchymal stromal cells ( 71 – 73 ).…”