Acute hematologic toxicity of radiation therapy – a comprehensive analysis and predictive nomogram

Abstract

To investigate radiation-induced cytopenia and establish predictive nomograms for hematological toxicity, we reviewed 3786 patients aged 18 or older who received radiation monotherapy between 2010 and 2021 for non-hematologic malignancies. We collected data on patient background, treatment content and hematologic toxicities for 12 weeks after the start of radiotherapy. The patients were randomly divided into training and test groups in 7:3 ratio. In the training group, we conducted ordered logistic regression analysis to identify predictive factors for neutropenia, lymphocytopenia, anemia and thrombocytopenia. Nomograms to predict Grade 2–4 cytopenia were generated and validated in the test group. Grade 3 or higher hematologic toxicities were observed in 9.7, 44.6, 8.3 and 3.1% of patients with neutropenia, lymphocytopenia, anemia and thrombocytopenia, respectively. We identified six factors for neutropenia grade, nine for lymphocytopenia grade and six for anemia grade with statistical significance. In the analysis of thrombocytopenia, the statistical model did not converge because of a small number of events. Nomograms were generated using factors with high predictive power. In evaluating the nomograms, we found high area under the receiver operating characteristic curve values (neutropenia; 0.75–0.85, lymphopenia; 0.89–0.91 and anemia; 0.85–0.86) in predicting Grade 2–4 cytopenia in the test group. We established predictive nomograms for neutropenia, leukocytopenia and anemia and demonstrated high reproducibility when validated in an independent cohort of patients.

Lymphocytopenia following adjuvant radiotherapy for breast cancer

“…Radiation‐induced lymphocytopenia is a common and usually non‐life‐threatening toxicity 11 . However, the association between lymphocytopenia after radiotherapy and patient outcomes has attracted increasing interest in recent years.…”

Lymphopenia after palliative radiotherapy for vertebral metastases

“…Previous studies have established a clinical correlation between lymphopenia and radiotherapy in patients with brain, head and neck, lung, esophageal, breast and cervical cancer [ 10–15 ]. In our recent study, we observed a reduction in blood cell count in a cohort of patients who received radiation monotherapy for various diseases [ 3 ]. In that study, Grade 3–4 lymphocytopenia after radiotherapy was observed in 45%.…”

“…This study received approval from the Institutional Review Board of Tohoku University Graduate School of Medicine (2021-1-1073). This study was a sub-analysis of a previous study in which prognostic factors for patients with vertebral metastases were investigated [ 6 ], and it partially overlaps with another study in which blood cell reduction after radiation monotherapy was comprehensively analyzed [ 3 ]. The methodology is described only briefly here as the previous publications contain detailed information about the patient cohort and treatment methods.…”

“…Lymphocytes are highly sensitive to radiation, which makes them vulnerable to interphase death even with exposure to low doses of radiation [ 1 ]. In cancer treatment, radiation therapy has been known to cause lymphopenia [ 2 , 3 ]. We have previously reported that the overall incidence rate of grade 3 lymphopenia following radiotherapy was 45% [ 3 ].…”

“…In cancer treatment, radiation therapy has been known to cause lymphopenia [ 2 , 3 ]. We have previously reported that the overall incidence rate of grade 3 lymphopenia following radiotherapy was 45% [ 3 ]. In that study, lymphopenia was observed across various types of radiotherapy, including different irradiation sites, field sizes and dose fraction schedules.…”