Predicting Severe Hematologic Toxicity from Extended-Field Chemoradiation of Para-Aortic Nodal Metastases from Cervical Cancer
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BACKGROUND AND PURPOSE: To determine significant factors predictive for severe hematologic toxicity (HT) in cervical cancer patients with para-aortic lymph node (PALN) metastasis treated with concurrent chemoradiation with a specific focus on radiation dose to total bone marrow (BMTOT) and active bone marrow (BMACT). To create a nomogram using significant factors to predict HT in these patients. MATERIAL AND METHODS: 38 Patients with cervical cancer and PALN metastasis who underwent 18F-FDG-PET / CT before treatment with extended field radiation therapy (EFRT) and concurrent cisplatin were analyzed. BMACT was defined as the region within BMTOT with a standardized uptake value (SUV) greater than or equal to the mean for the individual. Blood counts were collected weekly from the beginning of radiation treatment to the end of radiation treatment. HT was graded based on the guidelines set by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0. RESULTS: 19 patients (50%) had Grade 3 or higher hematologic toxicity (HT3+), not including lymphocyte toxicity. Patients who were obese (n=12) were less likely to get HT3+ compared to patients who were not obese (p=0.03) despite getting the same weight related dose of chemotherapy. Volume of BMTOT receiving 20 Gy, 30 Gy, and 45 Gy were significant predictors for HT3+ at 78.56% (p=0.01), 47.14% (p=0.00), and 20.36% (p=0.01) respectively. Volume of BMACT receiving 10 Gy, 20 Gy, 30 Gy, and 45 Gy were significant predictors for HT3+ at 95.50% (p=0.03), 80.52% (p=0.05), 59.64% (p=0.03), and 31.74% (p=0.01) respectively. Through logistic regression, the probability of developing HT3+ is given by the equation: Prob(HT3+) = 1 / (1 + exp(7.34 + 0.22*BMI - 0.44*Mean Dose to BMTOT)). Patients who had HT3+ received an average of 4 cycles of chemotherapy and 62 days of treatment time, significantly different than the 4.74 chemotherapy cycles and 53 days of treatment in patients without HT3+ (p=0.05, 0.00 respectively). CONCLUSIONS: Both higher patient BMI and bone marrow irradiation were associated with HT3+. A simplified nomogram has been created to predict HT3+ in these patients. Radiation parameters have been identified for cervical cancer patients with PALN involvement receiving EFRT concurrently with chemotherapy. Bone marrow sparing approaches for EFRT need to be addressed to improve patient care.