Retrospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Oct 15, 2019; 11(10): 857-865
Published online Oct 15, 2019. doi: 10.4251/wjgo.v11.i10.857
Retrospective review of total neoadjuvant therapy
Laila Babar, Veli Bakalov, Stephen Abel, Obaid Ashraf, Gene Grant Finley, Moses S Raj, Kristina Lundeen, Dulabh K Monga, Alexander V Kirichenko, Rodney E Wegner
Laila Babar, Veli Bakalov, Obaid Ashraf, Department of Internal Medicine, Allegheny General Hospital, Pittsburgh, PA 15212, United States
Stephen Abel, Alexander V Kirichenko, Rodney E Wegner, Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, PA 15212, United States
Gene Grant Finley, Moses S Raj, Kristina Lundeen, Dulabh K Monga, Department of Medical Oncology, Allegheny General Hospital, Pittsburgh, PA 15212, United States
Author contributions: Babar L and Wegner R designed the study; Babar L, Bakalov V, and Abel S performed the statistical analysis; Babar L wrote the paper; Ashraf O, Finley GG, Raj MS, Lundeen K, Monga DK, Kirichenko AV, and Wegner R contributed to the scientific review; Wegner R was the faculty mentor for this project.
Institutional review board statement: The IRB has reviewed this information and finds that this protocol does not fall under the purview of the IRB as it does not meet the definition of human subject research according to the federal code of regulations: 45 CFR 46.102(f).
Informed consent statement: As the data used was accessed via a public national database with deidentified patients, there was no need for informed consent.
Conflict-of-interest statement: The authors have no conflict of interest to report.
Data sharing statement: Data from this manuscript will be available upon request.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Laila Babar, MD, Doctor, Resident Physician, Department of Internal Medicine, Allegheny General Hospital, 320 E North Ave, Pittsburgh, PA 15212, United States. laila.babar@ahn.org
Telephone: +1-412-6520419
Received: February 27, 2019
Peer-review started: February 27, 2019
First decision: April 11, 2019
Revised: May 1, 2019
Accepted: September 12, 2019
Article in press: September 12, 2019
Published online: October 15, 2019
Processing time: 231 Days and 15 Hours
Abstract
BACKGROUND

Neoadjuvant chemoradiotherapy (nCRT) followed by resection and postoperative multi-agent chemotherapy (maChT) is the standard of care for locally advanced rectal cancer. Using this approach, maChT administration can be delayed for several months, leading to concern for distant metastases. To counteract this, a novel treatment approach known as total neoadjuvant therapy (TNT) has gained popularity, in which patients receive both maChT and nCRT prior to resection. We utilized the National Cancer Database to examine temporal trends in TNT usage, and any potential effect on survival.

AIM

To study the temporal trends in the usage of TNT and evaluate its efficacy compared to neoadjuvant chemoradiation.

METHODS

We queried the National Cancer Database for patients with locally advanced rectal cancer, Stage II-III, from 2004-2015 treated with nCRT or TNT. TNT was defined as maChT initiated ≥ 90 d prior to nCRT initiation. Overall survival was calculated from the date of diagnosis to the date of last contact or death using Kaplan-Meier curves to present the cumulative probability of survival, with log-rank statistics to assess significance. Multivariable cox regression was used to identify predictors of survival and propensity score analysis accounted for bias.

RESULTS

We identified 9066 eligible patients, with 8812 and 254 patients receiving neoadjuvant chemoradiation followed by maChT and TNT, respectively. Nodal involvement, stage III disease, and treatment in recent years were predictive of TNT use. There was greater use of TNT with more advanced stage, specifically > 1 node involved (odds ratio [OR] = 2.88, 95% confidence interval [CI]: 2.11-3.93, P < 0.01) and stage III disease (OR = 2.88, 95%CI: 2.11-3.93, P < 0.01). From 2010 to 2012 the use of TNT increased (OR = 2.41, 95%CI: 1.27-4.56, P < 0.01) with a greater increase from 2013 to 2015 (OR = 6.62, 95%CI: 3.57-12.25, P < 0.01). Both the TNT and neoadjuvant chemoradiation arms had a similar 5-year survival at 76% and 78% respectively. Multivariable analysis with propensity score demonstrated that increased age, high comorbidity score, higher grade, African American race, and female gender had worse overall survival.

CONCLUSION

Our data demonstrates a rising trend in TNT use, particularly in patients with worse disease. Patients treated with TNT and nCRT had similar survival. Randomized trials evaluating TNT are underway.

Keywords: Total neoadjuvant therapy; Neoadjuvant chemoradiation; Multi-agent chemotherapy; Locally advanced rectal cancer; National cancer database; Colorectal cancer; Retrospective review; Gastrointestinal oncology; Temporal trends; Surgical excision

Core tip: Total neoadjuvant treatment (TNT) has been gaining favor as the treatment of choice for rectal carcinoma. It has been linked to better sphincter preservation and overall improved quality of life. Our study aim was to compare TNT with traditional chemotherapy and radiation over the last 10 years and evaluate the differences in outcomes. Our study confirms a rising trend in the of use of TNT especially in patients diagnosed with locally advanced rectal cancer. Patients treated with TNT had higher burden of disease but had similar survival outcomes as those treated with traditional chemotherapy and radiation.