Journal of Gastrointestinal & Digestive System
Open Access

Abstract

Background: We previously showed that 75% of radiation treatment failures in patients with unresectable esophageal cancer appear within the gross tumor volume (GTV) and that use of a simultaneous integrated boost (SIB) could be used to escalate the radiation dose to the GTV. Based on this work a phase I trial was initiated at MD Anderson to find the maximum tolerated dose (MTD) of such a boost. MTD was defined as the highest dose associated with grade 3-4 esophagitis rates of ≥30%; esophagitis was scored according to V3 of the Common Terminology Criteria for Adverse Events. Initial findings from this trial are presented here. Methods: This study opened in February 2010 and enrolled 15 patients with unresectable esophageal cancer (10 men, 5 women) with good performance status (Karnofsky score ≥70). Patients were treated with concurrent chemotherapy (docetaxel and 5-fluorouracil) and radiation to a dose of 50.4 Gy given in 28 daily 1.8-Gy fractions to the planning target volume (PTV) via intensity-modulated radiation therapy (IMRT). The dose to the gross tumor volume (GTV, defined with endoscopic ultrasonography, positron emission tomography, or computed tomography) was limited to ≤10 cm of esophageal length. Dose to the GTV was to be escalated via SIB starting at 2.1 Gy per day and increasing to 2.25 Gy per day in a 3 � 3 dose-escalation design. Corrections were made for lung heterogeneity on all treatment plans. Results: All 15 patients (median age 65 y; mean age for men 62.2, mean age for women 63.2 y) completed SIB-IMRT. Three patients received a GTV boost dose of 58.8 Gy, and the other 12 patients received the highest planned boost dose of 63 Gy. Six patients had acute grade 2 esophageal toxicity, three acute grade 3 esophageal toxicity (all prior to starting radiation), and none had grade 4 or 5 treatment-related esophageal toxicity. Two patients experienced late esophageal toxicity (stricture requiring dilation). Seven patients had feeding tubes placed, all prior to radiation. At a median follow-up interval of 21 months, 12 patients were alive, 4 with recurrent disease. One patient underwent esophagectomy after completing the radiation therapy, and no viable tumor was identified. Conclusions: Early findings suggest that an SIB to the GTV for unresectable esophageal cancer was well tolerated, with toxicity comparable to that of historical control subjects. Longer follow-up is needed to assess potential benefits in local control or surviv

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