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.
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.
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.
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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