Results of a Phase 1/2 Trial of Chemoradiotherapy With Simultaneous Integrated Boost of Radiotherapy Dose in Unresectable Locally Advanced Esophageal Cancer
Authors: Wayne L Hofstetter
Mariela A Blum
Jeremy J Erasmus
Manoop S Bhutani
Vivek Verma
Jeffrey H Lee
James W Welsh
Jaffer A Ajani
Steven N Seyedin
Quynh-Nhu Nguyen
Hampartsoum B Barsoumian
Joe Y Chang
Bruce D Minsky
Kenneth R Hess
Stephen G Swisher
Daniel R Gomez
Dawei Chen
Arya Amini
Ahmed I Younes
Hari Menon
Journal: JAMA Oncology (2019)
Discipline: CLINICAL MEDICINE
Keywords: locally advanced esophageal cancer; chemoradiotherapy; simultaneous integrated boost; toxic effects; local control
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, 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, City of Hope National Medical Center, Duarte, California., Department of Surgery, 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 Biostatistics, The University of Texas MD Anderson Cancer Center, Houston.

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. 

Retracted: No

PubPeer comments:
 Below: Fig. 8,  Fluorescence photomicrograph of **liver tissue** sac after 45-min administration of FITC labeled a plain drug solution, **b N-SucCSNP**, and **c Lac-N-Suc-CSNP** . Above: Fig 7 from [Bilthariya et al (2015)] ,  Fluorescence photomicrograph of **inflamed joint tissue** sac after 45-min administration of FITC labelled (A) plain drug solution, **(B) ETX-NPs and (C) F-ETX-NPs**. ![file] , 
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 #2 Please compare Fig 5 with Fig 4 from [Jain et al (2014)] ,  Transmission electron microscope photomicrograph of (a) chitosan nanoparticles and (b) glycyrrhizin conjugated low molecular weight chitosan nanoparticles. ![] 4(a) and 5(a) appear to be identical, despite the quite different descriptions. Below, the present 5(b) is at right, and 4(b) from the companion paper at the left... one or other (or both) has undergone manipulations. ![] , 
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