Increasing Radiation Dose to the Thoracic Marrow Is Associated With Acute Hematologic Toxicities in Patients Receiving Chemoradiation for Esophageal Cancer.

Denise Fabian,Ahmet Ayan,Jose G Bazan,Dominic Dicostanzo,Eric D Miller,Christian L Barney,Terence M Williams,Evan Wuthrick,Dayssy A Diaz,Jihad Aljabban

doi:10.3389/fonc.2019.00147

Abstract

Purpose: To test the hypothesis that increasing radiation dose to the thoracic marrow (TM) contributes to the development of hematologic toxicities (HT) in esophageal cancer (EC) patients receiving chemoradiation therapy (CRT).Methods: We identified EC cases treated with curative intent CRT at our institution from 2007 to 2016. The TM was contoured as the union of the vertebral bodies (VB) from T1-L1, the ribs from T1-L1, and the sternum. The TM-mean dose and the TM volume receiving at least 5–50 Gy (V5-V50) were collected. Grade ≥ 3 HT (HT3+) was the primary endpoint. Normal tissue complication probability (NTCP) was evaluated using the Lyman-Kutcher-Burman (LKB) model. Logistic regression was used to test associations between HT3+ and dosimetric parameters. Odds ratios (OR) and 95% confidence intervals (CI) are reported with p < 0.05 considered significant. Receiver operating characteristics analysis was used to determine optimal cut points.Results: We identified 137 EC cases, and most received concurrent carboplatin/paclitaxel (N = 83). Median radiation dose was 50.4 Gy (IQR = 50.4–50.4 Gy). The rate of HT3+ was 39.4%. Optimization of the LKB model yielded the results n = 0.70, m = 0.67, and TD50 = 20.1 Gy. The TM-V30 was most strongly associated with HT3+ and on multivariate analysis, patients with TM-V30 ≥ 14% had a 5.7-fold (95% CI 2.42–14.54, p < 0.001) increased odds of HT3+ in the entire cohort and a 4-fold (95% CI 1.54–11.11, p = 0.006) increased odds of HT3+ in the carboplatin/paclitaxel cohort compared to patients with TM-V30 < 14%. Radiation dose to the VB and rib sub-sites of the TM were also associated with HT3+, particularly VB-V40.Conclusion: We found that increasing TM radiation dose was associated with HT3+ in EC patients treated with CRT. Radiation dose to the VB and rib sub-sites were also associated with HT3+. These findings suggest that limiting radiation dose to the TM (or its sub-sites) may be sufficient to decrease HT3+, but further prospective evaluation of these results is needed.

Highlights

Esophageal cancer is a common malignancy and leads to 16,000 deaths in the United States each year [1]
We found that increasing thoracic marrow (TM) radiation dose is associated with the development of acute HT3+ in esophageal cancer patients treated with CRT
In our NTCP analysis for the entire cohort, we found that the n value in the LKB model was close but not exactly equal to 1 (n = 0.70) and in the carboplatin/paclitaxel cohort, our results demonstrated that n = 0.30

Summary

Introduction

Esophageal cancer is a common malignancy and leads to 16,000 deaths in the United States each year [1]. Myelosuppression is a negative prognostic factor in patients undergoing CRT for esophageal cancer [4, 6]. Previous reports have suggested that greater radiation (RT) doses to the thoracic VB during CRT for lung cancer are associated with greater rates of HT [7, 8]. In 2016, a report of 46 esophageal cancer patients receiving CRT with cisplatin and 5-fluorouracil found greater thoracic VB and rib irradiation to be associated with grade 3 leukopenia [9]. Efforts to reduce radiation dose to the thoracic marrow (TM) may lead to reductions in HT. In the era of intensity modulated radiation therapy (IMRT), reducing the dose to the TM is potentially achievable

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