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Original Investigation | Pacific Coast Surgical Association

Association of Intervals Between Neoadjuvant Chemoradiation and Surgical Resection With Pathologic Complete Response and Survival in Patients With Esophageal Cancer ONLINE FIRST

Kelly R. Haisley, MD1; Amy E. Laird, PhD2; Nima Nabavizadeh, MD3; Ken M. Gatter, MD, JD4; John M. Holland, MD3; Gina M. Vaccaro, MD5; Charles R. Thomas Jr, MD3; Paul H. Schipper, MD6; John G. Hunter, MD1; James P. Dolan, MD, MCR1
[+] Author Affiliations
1Division of Gastrointestinal and General Surgery, Department of Surgery, Oregon Health and Science University, Portland
2Division of Biostatistics, School of Public Health, Oregon Health and Science University, Portland
3Department of Radiation Medicine, Oregon Health and Science University, Portland
4Department of Pathology, Oregon Health and Science University, Portland
5Division of Medical Oncology, Department of Medicine, Oregon Health and Science University, Portland
6Division of Cardiovascular and General Thoracic Surgery, Department of Surgery, Oregon Health and Science University, Portland
JAMA Surg. Published online September 14, 2016. doi:10.1001/jamasurg.2016.2743
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Importance  Pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (CRT) may be a clinical prognostic marker of superior outcomes. In patients with esophageal cancer, pCR is associated with increased survival. While mechanisms for increasing the likelihood of pCR remain unknown, in other solid tumors, higher rates of pCR have been associated with longer time intervals between CRT completion and surgical procedures.

Objective  To determine the association between time intervals from the completion of CRT to surgical procedure with rates of pCR in patients with esophageal cancer.

Design, Setting, and Participants  A prospectively maintained multidisciplinary foregut database was reviewed for consecutively enrolled patients with esophageal cancer from January 2000 to July 2015 presenting for surgical evaluation at a single National Cancer Institute–designated cancer center within a quaternary academic medical center.

Interventions  Included patients successfully completed neoadjuvant CRT followed by esophagectomy.

Main Outcomes and Measures  Rate of pCR by logistic regression based on a categorized time interval (ie, 0 to 42, 43 to 56, 57 to 70, 71 to 84, 85 to 98, and 99 or more days) from the completion of CRT to surgical resection, adjusted for clinical stage, demographic information, and CRT regimen.

Results  Of the 234 patients who met inclusion criteria, 191 (81.6%) were male, and the median (range) age was 64 (58-70) years; 206 (88.0%) were diagnosed as having adenocarcinoma, and 65 (27.9%) had a pCR. Patients in the 85 to 98–day group had significantly increased odds of a pCR compared with other groups (odds ratio, 5.46; 95% CI, 1.16-25.68; P = .03). No significant differences in survival were seen between time groups overall or among patients with residual tumor.

Conclusions and Relevance  This study suggests that a time interval of 85 to 98 days between CRT completion and surgical resection is associated with significantly increased odds of a pCR in patients with esophageal cancer. No adverse association with survival was detected as a result of delaying resection, even in patients with residual tumor.

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Figure 2.
Survival Probability Based on Time Interval Between Chemoradiotherapy and Surgical Resection

Kaplan-Meier estimate of the probability of survival after esophagectomy, stratified by groups defined by time between the end of neoadjuvant therapy and esophagectomy. A, The Wald test of coefficients for all patients demonstrated P = .47. B, The Wald test of coefficients for patients without a pathologic complete response demonstrated P = .17.

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