Sequential Short-Course Radiation Therapy and Chemotherapy in the Neoadjuvant Treatment of Rectal Cancer

Abstract

We report our single-institution experience with sequential short-course preoperative radiation therapy (5 Gy X 5 fractions) followed by preoperative chemotherapy for the treatment of patients with rectal adenocarcinoma, focusing on short-term oncologic and toxicity outcomes. We reviewed records of 26 patients with stage II or III rectal adenocarcinoma. All patients underwent short course radiation therapy (SCRT: 25 Gy in 5 fractions) followed by mFOLFOX6 or capecitabine plus oxaliplatin. The principle objectives were to assess treatment feasibility, treatment toxicity, and oncologic response. There were five clinical (c) T2, 16 cT3, and five cT4 cases, with 88% cN+. 25 patients received a median of 4 cycles (range 3 to 8) of mFOLFOX6 (with one cycle defined as a two-week period); one patient received 3 cycles of capecitabine and oxaliplatin. All patients completed SCRT; 81% completed the full course of neoadjuvant chemotherapy while 19% required dose reductions in chemotherapy, most commonly due to neuropathy (60%). Nineteen patients underwent post-treatment endoscopic evaluation, and 9 patients were noted to achieve a complete clinical response (CCR). Six patients who achieved CCR opted for a non-operative approach of watch and wait. Twenty patients underwent surgical resection. The median time from the end of SCRT to CCR (for patients followed with non-operative management) or surgical resection was 14.5 weeks (range 11.7 – 25.7 weeks). Negative resection margins were achieved in 18 of 20 patients who underwent surgery, and pathologic complete response was observed in 7 patients (35%) of these 20. The neoadjuvant rectal score was low in 50% of the patients who underwent surgery, and intermediate in 10%. The median follow-up time in the non-operative group was 15.6 weeks (range 2.7 – 42 weeks), and during this time local disease recurrence was noted in one patient at 20 weeks from time of CCR. The median follow-up time in the operative group was 24.3 weeks (range 3.7 – 49.3 weeks), during this time local disease recurrence was noted in one patient at 40 weeks from the time of surgery. The main radiation-associated toxicity was proctitis. CTCAE Grade 2 proctitis was observed in seven patients (27%). Post-operative Clavien-Dindo Grade 3 complications within 30 days of surgery were identified in six patients (30%), with no Grade 4 or 5 adverse events. Median length of hospital stay was 4.5 days (range 2-16 days); three patients were readmitted within a 30 day period. Short-course preoperative radiation therapy followed by chemotherapy was well-tolerated and achieved high rates of tumor response.