Preoperative radiation dose escalation for rectal cancer using a concomitant boost strategy improves tumor downstaging without increasing toxicity: A matched-pair analysis

Jillian R Gunther; Awalpreet S Chadha; Ui Sup Shin; In Ja Park; Kiran V Kattepogu; Jonathan D Grant; David C Weksberg; Cathy Eng; Scott E Kopetz; Prajnan Das; Marc E Delclos; Harmeet Kaur; Dipen M Maru; John M Skibber; Miguel A Rodriguez-Bigas; Y Nancy You; Sunil Krishnan; George J Chang

doi:10.1016/j.adro.2017.04.001

Preoperative radiation dose escalation for rectal cancer using a concomitant boost strategy improves tumor downstaging without increasing toxicity: A matched-pair analysis

Adv Radiat Oncol. 2017 Apr 12;2(3):455-464. doi: 10.1016/j.adro.2017.04.001. eCollection 2017 Jul-Sep.

Authors

Jillian R Gunther¹, Awalpreet S Chadha¹, Ui Sup Shin², In Ja Park², Kiran V Kattepogu², Jonathan D Grant¹, David C Weksberg¹, Cathy Eng³, Scott E Kopetz³, Prajnan Das¹, Marc E Delclos¹, Harmeet Kaur⁴, Dipen M Maru⁵, John M Skibber², Miguel A Rodriguez-Bigas², Y Nancy You², Sunil Krishnan¹, George J Chang^{2

6}

Affiliations

¹ Department of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
² Department of Surgical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
³ Department of Gastrointestinal Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
⁴ Department of Diagnostic Radiology, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
⁵ Department of Pathology, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
⁶ Department of Health Services Research, The University of Texas, MD Anderson Cancer Center, Houston, Texas.

Abstract

Purpose: Pathologic complete response to neoadjuvant chemoradiation therapy (CRT) is associated with improved outcomes for patients with locally advanced rectal cancer (LARC). Increased response rates have been reported with higher radiation doses, but these studies often lack long-term outcome and/or toxicity data. We conducted a case-control analysis of patients with LARC who underwent definitive CRT to determine the efficacy and safety of intensified treatment with a concomitant boost (CB) approach.

Methods and materials: From 1995 to 2003, a phase 2 protocol examined CRT with 5-fluorouracil and CB radiation therapy (52.5 Gy in 5 weeks) for patients with LARC. Seventy-six protocol patients were matched (case-control approach) for surgery type, tumor (T) stage, and clinical nodal (N) stage with patients who received standard dose (SD) CRT (5-fluorouracil, 45 Gy). A chart review was performed. McNemar's test and Kaplan-Meier analyses were used for statistical analysis.

Results: The SD and CB groups did not differ in tumor circumferential involvement and length, but the tumors of CB patients were closer to the anal verge (4.7 vs 5.7 cm; P = .02). Although tumor downstaging was higher in the CB cohort (76% vs 51%; P < .01), pathologic complete response rates did not differ (CB, 17.1% vs SD, 15.8%, P = 1.00). The incidence of grade ≥3 radiation-related toxicities was low and similar in both groups (CB, 10% vs SD, 3%, P = .22). Postoperative (anastomotic leak, wound complications/abscess, bleeding) and late (small bowel obstruction, stricture) complication rates did not differ between the groups (P > .05). The median follow-up was 11.9 years. The 5-year local control rates were higher for CB (100.0%) compared with SD (90.0%) patients (P = .01). CB patients had higher rates of 10-year progression-free survival (71.9% vs 57.6%, P < .01) and overall survival (71.6% vs 62.4%, P = .01) compared with SD patients.

Conclusions: CRT dose escalation for patients with LARC is safe and effective. The improved T-downstaging and local control observed in CB patients should encourage further dose escalation studies.

Grants and funding

P30 CA016672/CA/NCI NIH HHS/United States