A Dosimetric Study Indicates the Spinal Cord Irradiation Contributes to Acute Hematologic Toxicities in Non-Small Cell Lung Cancer Patients Receiving Radiotherapy Combined with Immunotherapy

Abstract

To assess the radiation therapy (RT) dose to radiation-associated hematologic toxicities (HTs) in patients with non-small cell lung cancer (NSCLC) after RT combined with immunotherapy. Cases of NSCLC treated with RT combined with immunotherapy at Shandong Cancer Hospital in China were identified. The mean dose and the volume of the spinal cord receiving at least 5 to 40 Gy (V5-V40) were retrospectively recorded. Logistic regression was used to estimate associations between grade ≥3 HT (HT3+) and dosimetric/clinical parameters. Receiver operating characteristic analysis was used to determine dosimetric cut-points. Ninety-nine patients were analyzed. The majority were male (n = 78, 78.8%) and received chemotherapy (n = 83, 83.9%). All patients received either anti-PD-1 immune checkpoint (n = 89, 89.9%) or anti-PD-L1 immune checkpoint (n = 10, 10.1%) therapy. The rate of HT3+ was 24.2% (n = 24). Spinal cord mean dose, V5 to V40 and BMI parameters associated with HT3+ were included in the multivariate analysis. On multivariate analysis, increasing mean spinal cord dose (per Gy) was associated with higher odds of developing HT3+ (odds ratio 1.053, 95% confidence interval 1.002-1.105, P = .041), as were increasing spinal cord V5 to V20 (As show in the Table below). The optimal cut-points identified were V5 = 52.5%, V10 = 47.5%, V20 = 39.4%, and mean dose = 23.3 Gy. Patients with values above these cut-points had an approximately 2-fold increased risk of HT3+. We found that mean spinal cord dose and low-dose parameters (V5-V20) were associated with HT3+ in NSCLC patients after RT and immunotherapy. The mean dose of the spinal cord should be kept lower than 23.3 Gy for these patients. These data suggested that efforts to spare doses to the spinal cord might reduce rates of severe HT.