Gastrointestinal Cancer

SS 17 - GI 3 - Colon/Rectum/Anus

130 - Rectal Cancer Downstaging is Significantly Improved with Different Regimens of Total Neoadjuvant Therapy

Monday, October 22
4:35 PM - 4:45 PM
Location: Room 214 C/D

Rectal Cancer Downstaging is Significantly Improved with Different Regimens of Total Neoadjuvant Therapy
W. Chapman, Jr Jr1, C. Roxburgh2, B. Makhdoom1, A. Roy3, F. F. Youssef3, P. Brady4, J. R. Olsen5, H. Kim Jr3, K. Pedersen6, M. Mutch1, S. Hunt1, S. Markovina7, C. Hajj4, A. Cercek8, M. Weiser4, and P. J. Parikh3; 1Washington University School of Medicine, Department of Surgery, St. Louis, MO, 2University of Glasgow, Department of Oncology, Glasgow, United Kingdom, 3Washington University School of Medicine, St. Louis, MO, 4Memorial Sloan Kettering Cancer Center, New York, NY, 5Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO, 6Washington University School of Medicine, Department of Medicine, Division of Hematology Oncology, St. Louis, MO, 7Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, 8Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY

Purpose/Objective(s): Total Neoadjuvant Therapy (TNT), delivery of all chemotherapy and radiation prior to resection, has been suggested to improve outcomes for patients with locally advanced rectal cancer. The Neoadjuvant Rectal score (NAR) is a validated early predictor of outcome using a semi-continuous variable for downstaging between clinical and pathologic stage. This study compares NAR scores achieved by standard chemoradiation (CRT) and two TNT regimens utilizing different radiation approaches: neoadjuvant short course radiation followed by chemotherapy (SC-TNT) and induction chemotherapy followed by long course chemoradiation (LC-TNT).

Materials/Methods: Patients undergoing neoadjuvant therapy for locally advanced rectal cancer at two US NCI-designated cancer centers were included for retrospective cohort analysis. Three different neoadjuvant regimens were evaluated: traditional CRT, which included 50-55 Gy / 25-28 fx with concurrent 5-FU or capecitabine; SC-TNT, comprised of 25Gy / 5 fx followed by FOLFOX/CAPOX chemotherapy; and LC-TNT, which had FOLFOX/CAPOX followed by standard chemoradiation. Patients then underwent total mesorectal excision or, in the setting of complete clinical response, nonoperative management. Primary outcome of NAR Score was calculated for each patient and categorized as “Low” (less than 8), “Intermediate” (8 – 16), or “High” (greater than 16). Nonoperatively managed patients with no evidence of recurrence at 12 months were classified as a complete pathologic response. Univariate analysis was performed with Kruskal-Wallace test; odds ratios of achieving NAR less than 8 were calculated.

Results: 912 patients with locally advanced rectal cancer underwent neoadjuvant therapy at our centers from 2009 to 2017. 498 patients (55%) underwent chemoradiation, 318 (35%) received LC-TNT, and 96 (10%) were treated with SC-TNT. On univariate analysis, the LC-TNT cohort was significantly younger (38% under 50 years old versus 24% and 26%, respectively) and had more advanced disease (85% Stage III tumors compared to 69% and 72%, respectively) compared to the CRT or SC-TNT cohorts. Odds of achieving a “Low” NAR were significantly higher among SC-TNT (OR=1.95; 95%CI 1.24 – 3.07) and LC-TNT (OR=2.09; 95%CI 1.55 – 2.82) compared to CRT. However, direct comparison between SC-TNT and LC-TNT yielded no significant difference (Table 1).

Conclusion: SC-TNT and LC-TNT both outperform traditional CRT but achieve similar tumor downstaging when directly compared in this large, multi-institutional cohort. These data highlight the need for a SC-TNT arm in prospective randomized studies evaluating rectal cancer downstaging and nonoperative management in the US. Table 1.
NAR Score Category
n Low NAR n (%) Intermediate NAR n (%) High NAR n (%)
CRT 498 131 (26) 236 (48) 131 (26)
SC-TNT 96 39 (41) 34 (35) 23 (24)
LC-TNT 318 136 (43) 118 (37) 64 (20)
Odds Ratios of Achieving NAR<8
Odds Ratio 95% CI
SC-TNT vs. CRT 1.95 1.24 3.07
LC-TNT vs. CRT 2.09 1.55 2.82
LC-TNT vs. SC-TNT 1.08 0.68 1.72

Author Disclosure: W. Chapman, Jr: None. C. Roxburgh: None. A. Roy: None. F.F. Youssef: None. P. Brady: None. J.R. Olsen: Senior Associate Editor; International Journal of Radiation Oncology Biolog. S. Hunt: None. S. Markovina: Research Grant; ASTRO, Elsa U Pardee Foundation. Abstract awards; ASTRO. A. Cercek: None. P.J. Parikh: Research Grant; Varian Medical, Viewray. Honoraria; Viewray. Speaker's Bureau; Sirtex. Advisory Board; Sirtex. Stock; Holaira.

William Chapman, Jr, MD

Disclosure:
No relationships to disclose.

Biography:
William Chapman, Jr MD MPHS
Research Fellow
Department of Surgery
Washington University School of Medicine

Dr. Chapman is a research fellow with the Section of Colon and Rectal Surgery at Washington University School of Medicine. After completing his clinical training in general surgery, he plans to pursue specialty training in colorectal surgery and an academic career in clinical outcomes and health services research. His principle academic interest is neoadjuvant treatment options in rectal cancer.

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