Abstract

BackgroundThere is continued debate regarding the optimal combinations of radiation therapy and chemotherapy in the preoperative treatment of locally advanced rectal adenocarcinomas. We report our single-institution experience of feasibility and early oncologic outcomes of short-course preoperative radiation therapy (5 Gy X 5 fractions) followed by consolidation neoadjuvant chemotherapy.MethodsWe reviewed the records of 26 patients with locally advanced rectal adenocarcinoma. All patients underwent short course radiotherapy (5 Gy X 5 fractions) followed by chemotherapy [either modified infusional and bolus 5-fluorouracail and oxalipatin (mFOLFOX6) or capecitabine and oxaliplatin] prior to consideration for surgery. A full course of chemotherapy was defined as at least 8 weeks of chemotherapy.ResultsThere were five clinical (c) T2, 16 cT3, and five cT4 rectal tumors, with 88% cN+. Twenty-five 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 with 19% requiring dose reductions in chemotherapy, most commonly due to neuropathy. Nineteen patients underwent post-treatment endoscopic evaluation, and nine patients were noted to achieve a complete clinical response (CCR). Six of the nine patients who achieved CCR opted for a non-operative approach of watch-and-wait. Twenty patients underwent surgical resection; pathologic complete response was observed in seven (35%) of these twenty. The main radiation-associated toxicity was proctitis with CTCAE Grade 2 proctitis 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.ConclusionsShort course preoperative radiotherapy followed by neoadjuvant chemotherapy was well-tolerated and achieved oncologic outcomes that compare favorably with short-course radiation therapy alone or long-course chemoradiotherapy. This regimen is associated with high rates of clinical and pathologic complete response.

Highlights

  • There is continued debate regarding the optimal combinations of radiation therapy and chemotherapy in the preoperative treatment of locally advanced rectal adenocarcinomas

  • Radiation has been administered in short-course fashion, typically 25 Gy delivered in 5 fractions, or concurrently with chemotherapy in more protracted chemoradiotherapy regimens

  • The Dutch TME trial demonstrated that preoperative short-course radiation therapy (SCRT) reduced the risk of local-regional recurrence risk relative to surgery alone, and preoperative chemoradiotherapy courses are likewise associated with low rates of pelvic tumor recurrence following surgery [1, 2]

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Summary

Introduction

There is continued debate regarding the optimal combinations of radiation therapy and chemotherapy in the preoperative treatment of locally advanced rectal adenocarcinomas. We report our single-institution experience of feasibility and early oncologic outcomes of short-course preoperative radiation therapy (5 Gy X 5 fractions) followed by consolidation neoadjuvant chemotherapy. Radiation therapy and chemotherapy are commonly used in the preoperative setting for selected patients with rectal adenocarcinoma. Radiation has been administered in short-course fashion, typically 25 Gy delivered in 5 fractions, or concurrently with chemotherapy in more protracted chemoradiotherapy regimens. The Dutch TME trial demonstrated that preoperative short-course radiation therapy (SCRT) reduced the risk of local-regional recurrence risk relative to surgery (total mesorectal excision) alone, and preoperative chemoradiotherapy courses are likewise associated with low rates of pelvic tumor recurrence following surgery [1, 2]. Chemotherapy has demonstrated the ability to achieve profound local effects on gross primary rectal tumors, including induction of pathologic complete responses [5,6,7,8]

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