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Original Investigation
September 17, 2019

Results of a Phase 1/2 Trial of Chemoradiotherapy With Simultaneous Integrated Boost of Radiotherapy Dose in Unresectable Locally Advanced Esophageal Cancer

Author Affiliations
  • 1Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston
  • 2Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, China
  • 3Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, Pennsylvania
  • 4Department of Radiation Oncology, University of Iowa Hospital and Clinics, Iowa City
  • 5Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston
  • 6Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston
  • 7Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California
  • 8Department of Surgery, The University of Texas MD Anderson Cancer Center, Houston
  • 9Department of Diagnostic Radiology-Thoracic Imaging, The University of Texas MD Anderson Cancer Center, Houston
  • 10Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston
  • 11Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston
JAMA Oncol. Published online September 17, 2019. doi:10.1001/jamaoncol.2019.2809
Key Points

Question  Does providing a simultaneous integrated boost to 63 Gy of radiotherapy for locally advanced esophageal cancer improve treatment efficacy without increasing toxic effects?

Findings  This single-arm phase 1/2 trial of 46 patients treated with chemoradiotherapy and given a simultaneous integrated boost of radiotherapy dose for unresectable locally advanced esophageal cancer showed promising local control rates, higher than rates for 97 similar patients who received a standard 50.4-Gy dose of radiotherapy without a simultaneous integrated boost. Toxic effects were mild, with no grade 4 to 5 adverse events.

Meaning  Use of a simultaneous integrated boost to 63 Gy of radiotherapy for locally advanced esophageal cancer merits further evaluation.

Abstract

Importance  Effective treatment options for locally advanced esophageal cancer are limited, and rates of local recurrence after standard chemoradiotherapy remain high.

Objective  To evaluate toxic effects, local control, and overall survival rates after chemoradiotherapy with a simultaneous integrated boost of radiotherapy dose to the gross tumor and nodal disease for patients with unresectable locally advanced esophageal cancer.

Design, Setting, and Participants  A phase 1/2, single-arm trial was conducted in 46 patients from April 28, 2010, to April 9, 2015 (median follow-up, 52 months [range, 2-86 months]), at a tertiary academic cancer center. Outcomes of the study patients were compared with those of 97 similar patients treated at the same institution from January 10, 2010, to December 5, 2014, as part of the interim analysis. Statistical analysis was performed from December 15, 2018, to February 12, 2019.

Interventions  Chemoradiotherapy with a simultaneous integrated boost of radiotherapy dose (50.4 Gy to subclinical areas at risk and 63.0 Gy to the gross tumor and involved nodes, all given in 28 fractions) with concurrent docetaxel and capecitabine or fluorouracil.

Main Outcomes and Measures  Toxic effects, local (in-field) control, and overall survival rates.

Results  All 46 patients (11 women and 35 men; median age, 65.5 years [range, 37.3-84.4 years]) received per-protocol therapy, as intensity-modulated photon therapy (39 [85%]) or intensity-modulated proton therapy (7 [15%]); 11 patients (24%) ultimately underwent resection. No patients experienced grade 4 or 5 toxic effects; the 10 acute grade 3 toxic events were esophagitis (4), dysphagia (3), and anorexia (3) and the 3 late grade 3 toxic events were all esophageal strictures. The actuarial local recurrence rates were 22% (95% CI, 11%-35%) at 6 months, 30% (95% CI, 18%-44%) at 1 year, and 33% (95% CI, 20%-46%) at 2 years. Overall, 15 patients (33%) experienced local failure, at a median interval of 5 months (range, 1-24 months). The median overall survival time was 21.5 months (range, 2.3-86.4 months). Exploratory comparison with a 97-patient contemporaneous institutional cohort receiving standard-dose (non–simultaneous integrated boost) chemoradiotherapy showed superior local control (hazard ratio, 0.49; 95% CI, 0.26-0.92; P = .03) and overall survival (hazard ratio, 0.66; 95% CI, 0.47-0.94; P = .02) in the group that received chemoradiotherapy with a simultaneous integrated boost.

Conclusions and Relevance  These findings suggest that chemoradiotherapy with a simultaneous integrated boost of radiotherapy dose for locally advanced esophageal cancer is well tolerated, with encouraging local control, and thus warrants further study.

Trial Registration  ClinicalTrials.gov identifier: NCT01102088

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