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

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

JOURNAL=Frontiers in Oncology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.00147

DOI=10.3389/fonc.2019.00147

ISSN=2234-943X

ABSTRACT=<p><bold>Purpose:</bold> 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).</p><p><bold>Methods:</bold> 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 <italic>p</italic> &lt; 0.05 considered significant. Receiver operating characteristics analysis was used to determine optimal cut points.</p><p><bold>Results:</bold> We identified 137 EC cases, and most received concurrent carboplatin/paclitaxel (<italic>N</italic> = 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 <italic>n</italic> = 0.70, <italic>m</italic> = 0.67, and TD<sub>50</sub> = 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, <italic>p</italic> &lt; 0.001) increased odds of HT3+ in the entire cohort and a 4-fold (95% CI 1.54–11.11, <italic>p</italic> = 0.006) increased odds of HT3+ in the carboplatin/paclitaxel cohort compared to patients with TM-V30 &lt; 14%. Radiation dose to the VB and rib sub-sites of the TM were also associated with HT3+, particularly VB-V40.</p><p><bold>Conclusion:</bold> 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.</p>