Vertebral Bone Marrow Irradiation Contributes to Hematologic Toxicity During Chemoradiation Therapy for Esophageal Cancer

Abstract

Hematological toxicity (HT) commonly occurs during chemoradiation therapy (CRT) for esophageal cancer, with both modalities contributing to the decline in blood counts. Since leukopenia commonly precludes chemotherapy delivery, we sought to determine the dose volume histogram (DVH) constraints that correlate with decline in leukocyte counts due to comprehensive vertebra (CV) irradiation during CRT. 32 esophageal cancer patients treated with weekly neoadjuvant CRT were selected to be in the study. The typical chemotherapy regimen consisted of weekly intravenous carboplatin (area under the curve = 2) and paclitaxel (50 mg/m2). Radiation therapy (RT) was delivered using 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT). Patients who missed CRT for reasons other than neutropenia or received colony-stimulating factors were excluded. HT was scored using the Common Terminology Criteria for Adverse Events version 4.0. CV were contoured from C2 to L2 vertebra on 4DCT simulation scans. DVH data in both percentages and cubic centimeters was collected for CV V10-V60 (CVV) in increments of 10s. CVV5 and mean vertebral dose (MVD) were included as well. A DVH parameter of Vx was defined as either the percentage or volume in cubic centimeters of organ receiving at least x Gy of radiation. Univariate linear regression was performed to identify associations between leukopenia nadirs and DVH parameters. β represents the change in blood counts in k/μL for every 1 unit increase in DVH parameter. Receiver operator curves demonstrate cutoffs to avoid grade ≥ 3 leukopenia. Of the 32 esophageal patients, 6 patients developed grade 1 leukopenia, 12 developed grade 2 leukopenia, 8 developed grade 3 leukopenia, and 3 developed grade 4 leukopenia. CVV30, CVV20, CVV10, and MVD were significantly associated with decreasing WBC when calculated either as a percentage or by volume of the organ on univariate analysis. CVV5 was significantly associated with decreasing WBC counts only when calculated as a percentage of the volume and not as volume by cubic centimers. Associations with leukopenia were not seen with higher DVH values. CVV60, CVV50, and CVV40 did not significantly influence WBC levels during CRT. Cutoffs to avoid grade ≥ 3 leukopenia were CVV20 < 44.3%, CVV10 < 54.2%, CVV20 < 225 cc, CVV10 < 260 cc, and MVD < 18.8 Gy.< table class=”abstracttable>< tbody>< tr> CVV30 CVV20 CVV10 CVV5 MVD WBC (DVH by %) β p-value . -0.00528 0.0154 . -0.00767 0.0016 . -0.00826 0.0005 . -0.00828 0.0005 . -0.00014 0.0125 WBC (DVH by cc) . . . . . β p-value -0.00111 0.022 -0.00109 0.0269 -0.00107 0.0268 -0.000804 0.0577 -0.00014 0.0125 Leukopenia is associated with higher RT doses to the CVV30, CVV20, CVV10, CVV5, and MVD during CRT for esophageal cancer patients. Improved low dose radiation sparing of the CV may decrease HT.