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Original Investigation
March 8, 2017

Association Between Incomplete Neoadjuvant Radiotherapy and Survival for Patients With Locally Advanced Rectal Cancer

Author Affiliations
  • 1Student, Duke University School of Medicine, Durham, North Carolina
  • 2Department of Surgery, Duke University, Durham, North Carolina
  • 3Department of Radiation Oncology, Duke University, Durham, North Carolina
JAMA Surg. Published online March 8, 2017. doi:10.1001/jamasurg.2017.0010
Key Points

Question  Is incomplete radiotherapy in rectal cancer associated with worse outcomes?

Findings  This analysis of 17 600 adults with stage II to III rectal adenocarcinoma from the 2006-2012 National Cancer Database who received neoadjuvant chemoradiotherapy before surgical resection showed that a complete radiation dose significantly lowers the risk of long-term mortality vs an incomplete radiation dose. Patients receiving radiotherapy and surgery at different facilities were less likely to complete radiotherapy.

Meaning  In patients with rectal cancer, aligning multimodal care is associated with increased neoadjuvant radiotherapy completion, and completion is associated with increased survival.

Abstract

Importance  Failing to complete chemotherapy adversely affects survival in patients with colorectal cancer. However, the effect of incomplete delivery of neoadjuvant radiotherapy is unclear.

Objective  To determine whether incomplete radiotherapy delivery is associated with worse clinical outcomes and survival.

Design, Setting, and Participants  Data on 17 600 patients with stage II to III rectal adenocarcinoma from the 2006-2012 National Cancer Database who received neoadjuvant chemoradiotherapy followed by surgical resection were included. Multivariable regression methods were used to compare resection margin positivity, permanent colostomy rate, 30-day readmission, 90-day mortality, and overall survival between patients who received complete (45.0-50.4 Gy) and incomplete (<45.0 Gy) doses of radiation as preoperative therapy.

Main Outcomes and Measures  The primary outcome measure was overall survival; short-term perioperative and oncologic outcomes encompassing margin positivity, permanent ostomy rate, postoperative readmission, and postoperative mortality were also assessed.

Results  Among 17 600 patients included, 10 862 were men, with an overall median age of 59 years (range, 51-68 years). Of these, 874 patients (5.0%) received incomplete doses of neoadjuvant radiation. The median radiation dose received among those who did not achieve complete dosing was 34.2 Gy (interquartile range, 19.8-40.0 Gy). Female sex (adjusted odds ratio [OR] 0.69; 95% CI, 0.59-0.81; P < .001) and receiving radiotherapy at a different hospital than the one where surgery was performed (OR, 0.72; 95% CI, 0.62-0.85; P < .001) were independent predictors of failing to achieve complete dosing; private insurance status was predictive of completing radiotherapy (OR, 1.60; 95% CI, 1.16-2.21; P = .004). At 5-year follow-up, overall survival was improved among patients who received a complete course of radiotherapy (3086 [estimated survival probability, 73.2%] vs 133 [63.0%]; P < .001). After adjustment for demographic, clinical, and tumor characteristics, patients receiving a complete vs incomplete radiation dose had a similar resection margin positivity (OR, 0.99; 95% CI, 0.72-1.35; P = .92), permanent colostomy rate (OR, 0.96; 95% CI, 0.70-1.32; P = .81), 30-day readmission rate (OR, 0.92; 95% CI, 0.67-1.27; P = .62), and 90-day mortality (OR, 0.72; 95% CI, 0.33-1.54; P = .41). However, a complete radiation dose had a significantly lower risk of long-term mortality (adjusted hazard ratio, 0.70; 95% CI, 0.59-0.84; P < .001).

Conclusions and Relevance  Achieving a target radiation dose of 45.0 to 50.4 Gy is associated with a survival benefit in patients with locally advanced rectal cancer. Aligning all aspects of multimodal oncology care may increase the probability of completing neoadjuvant therapy.

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