Treatment Option Overview
The other large and ongoing study in the United States, NSABP-R-04, is evaluating the role of capecitabine and oxaliplatin administered concurrently with radiation therapy. NSABP-R-04 is randomly assigning patients in a 2 × 2 factorial design to one of the following four treatment groups for clinically staged T3 or T4 or node-positive rectal cancer:
- Intravenous continuous infusion (IVCI) 5-FU with radiation therapy.
- Capecitabine with radiation therapy.
- IVCI 5-FU plus weekly oxaliplatin with radiation therapy.
- Capecitabine plus weekly oxaliplatin with radiation therapy.
The primary objective of this study is locoregional disease control.
The acute side effects of pelvic radiation therapy for rectal cancer are mainly the result of gastrointestinal toxicity, are self-limiting, and usually resolve within 4 to 6 weeks of completing treatment. Of greater concern is the potential for late morbidity following rectal cancer treatment. Patients who undergo aggressive surgical procedures for rectal cancer can have chronic symptoms, particularly if there is impairment of the anal sphincter. Patients treated with adjuvant radiation therapy appear to have increased chronic bowel dysfunction, anorectal sphincter dysfunction (if the sphincter was surgically preserved), and sexual dysfunction than those who undergo surgical resection alone.[17,36,37,38,39,40,41]
A Cochrane review highlights the risks of increased surgical morbidity as well as late rectal and sexual function in association with adjuvant therapy. Improved radiation planning and techniques may minimize these acute and late treatment-related complications. These techniques include:[42,43,44]
- The use of high-energy radiation machines.
- The use of multiple pelvic fields.
- Prone patient positioning.
- Customized patient molds (belly boards) to exclude as much small bowel as possible from the fields and immobilize patients during treatment.
- Bladder distention during radiation therapy to exclude as much small bowel as possible from the fields.
- Visualization of the small bowel through oral contrast during treatment planning so that when possible, the small bowel can be excluded from the radiation field.
- The use of three dimensional or other advanced radiation planning techniques.
In Europe, it is common to deliver preoperative radiation therapy alone in one week (5 Gy x 5 daily treatments) followed by surgery one week later, as compared to the long-course chemoradiation approach in the United States. One reason for this difference is the concern in the U.S. for heightened late effects with high radiation doses per fraction. A Polish study randomized 316 patients between preoperative long course chemoradiation (50.4 Gy in 28 daily fractions with 5-FU and folinic acid) and short-course preoperative radiation therapy (25 Gy in 5 fractions). Although the primary endpoint was sphincter preservation, late toxicity was not statistically significantly different between the two treatment approaches (7% long course vs. 10% short course). Of note, data on anal sphincter and sexual function were not reported, and toxicity was physician determined, not patient reported. Ongoing clinical trials comparing preoperative and postoperative adjuvant chemoradiation therapy should further clarify the impact of either approach on bowel function and other important quality-of-life issues (e.g., sphincter preservation) in addition to the more conventional endpoints of DFS and OS.
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