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Results of a Phase 1/2 Trial of Chemoradiotherapy With Simultaneous Integrated Boost of Radiotherapy Dose in Unresectable Locally Advanced Esophageal Cancer.
JAMA Oncol 2019JO

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.

Authors+Show Affiliations

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston. Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, China.Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, Pennsylvania.Department of Radiation Oncology, University of Iowa Hospital and Clinics, Iowa City.Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston.Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston.Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California.Department of Surgery, The University of Texas MD Anderson Cancer Center, Houston.Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston.Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.Department of Diagnostic Radiology-Thoracic Imaging, The University of Texas MD Anderson Cancer Center, Houston.Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston.Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston.Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston.Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31529018

Citation

Chen, Dawei, et al. "Results of a Phase 1/2 Trial of Chemoradiotherapy With Simultaneous Integrated Boost of Radiotherapy Dose in Unresectable Locally Advanced Esophageal Cancer." JAMA Oncology, 2019.
Chen D, Menon H, Verma V, et al. Results of a Phase 1/2 Trial of Chemoradiotherapy With Simultaneous Integrated Boost of Radiotherapy Dose in Unresectable Locally Advanced Esophageal Cancer. JAMA Oncol. 2019.
Chen, D., Menon, H., Verma, V., Seyedin, S. N., Ajani, J. A., Hofstetter, W. L., ... Welsh, J. W. (2019). Results of a Phase 1/2 Trial of Chemoradiotherapy With Simultaneous Integrated Boost of Radiotherapy Dose in Unresectable Locally Advanced Esophageal Cancer. JAMA Oncology, doi:10.1001/jamaoncol.2019.2809.
Chen D, et al. Results of a Phase 1/2 Trial of Chemoradiotherapy With Simultaneous Integrated Boost of Radiotherapy Dose in Unresectable Locally Advanced Esophageal Cancer. JAMA Oncol. 2019 Sep 17; PubMed PMID: 31529018.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Results of a Phase 1/2 Trial of Chemoradiotherapy With Simultaneous Integrated Boost of Radiotherapy Dose in Unresectable Locally Advanced Esophageal Cancer. AU - Chen,Dawei, AU - Menon,Hari, AU - Verma,Vivek, AU - Seyedin,Steven N, AU - Ajani,Jaffer A, AU - Hofstetter,Wayne L, AU - Nguyen,Quynh-Nhu, AU - Chang,Joe Y, AU - Gomez,Daniel R, AU - Amini,Arya, AU - Swisher,Stephen G, AU - Blum,Mariela A, AU - Younes,Ahmed I, AU - Barsoumian,Hampartsoum B, AU - Erasmus,Jeremy J, AU - Lee,Jeffrey H, AU - Bhutani,Manoop S, AU - Hess,Kenneth R, AU - Minsky,Bruce D, AU - Welsh,James W, Y1 - 2019/09/17/ PY - 2019/9/19/entrez JF - JAMA oncology JO - JAMA Oncol N2 - 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. SN - 2374-2445 UR - https://www.unboundmedicine.com/medline/citation/31529018/Results_of_a_Phase_1/2_Trial_of_Chemoradiotherapy_With_Simultaneous_Integrated_Boost_of_Radiotherapy_Dose_in_Unresectable_Locally_Advanced_Esophageal_Cancer L2 - https://jamanetwork.com/journals/jamaoncology/fullarticle/10.1001/jamaoncol.2019.2809 DB - PRIME DP - Unbound Medicine ER -