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Radiotherapy, concomitant protracted-venous-infusion 5-fluorouracil, and surgery for ultrasound-staged T3 to T4 rectal cancer

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Diseases of the Colon & Rectum

Abstract

BACKGROUND: A prospective study was undertaken to evaluate the response and toxicity of neoadjuvant chemoradiotherapy for ultrasound-staged T3 or T4 rectal cancer. PATIENTS AND METHODS: Since 1995, 30 patients (18 males; median age, 56 (range, 25–83) years) have received preoperative chemoradiotherapy for ultrasound-staged T3 or T4 rectal cancer. All patients underwent an endorectal ultrasound, CT scan, and review in our multidisciplinary Gastrointestinal Tumor Board before treatment. All patients had pathology-demonstrated invasive adenocarcinoma of the rectum. Eleven patients were Stage T3N0, 14 were T3N1, and five were T4N1. Patients received radiotherapy to the primary tumor and draining lymph nodes (45 Gy) followed by a tumor boost (50.4–54 Gy). Protracted-venous-infusion 5-fluorouracil (225 mg/m2 per day, seven days per week) was administered throughout treatment. Surgical resection was performed six to ten weeks after completing chemoradiotherapy. Using endorectal ultrasound measurements, the primary tumor was a median of 4 (range, 0–12) cm from the anal verge, encompassed 50 (range, 20–90) percent of the rectal circumference, and was 6 (range, 3–12) cm in diameter. RESULTS: No Grade 4 toxicity was observed during chemoradiotherapy. Three patients experienced Grade 3 toxicity (diarrhea), and four patients required a treatment interruption of greater than three days. All patients completed at least 90 percent of the prescribed radiotherapy dose. All patients underwent surgical resection. Ninety-four percent had clear surgical margins. All pathologic specimens had significant evidence of necrosis, hyalinization, and fibrosis. Thirty-three percent of the specimens had a complete pathologic response (defined as no evidence of viable tumor cells). Of the 19 patients with ultrasound-staged N1 disease, only five had pathologic evidence of nodal involvement after chemoradiotherapy. Of the 25 patients with ultrasound-staged T3 disease, pathologic staging revealed eight with T0, two with T1, five with T2, and ten with T3 disease. Of the five patients with ultrasound-staged T4 disease, pathologic staging revealed two with T0, one with T2, and two with T3 disease. No patient developed progressive disease while on treatment. Two patients have experienced local failure at 6 and 20 months, and one patient failed in the liver at seven months. Twenty-seven patients remain free of disease with a median follow-up of 20 (range, 3–53) months. CONCLUSION: Our experience suggests that preoperative chemoradiotherapy is well tolerated, down-stages tumors, and sterilizes regional lymph nodes.

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Authors and Affiliations

  1. From the Department of Medicine, Division of Oncology, Stanford University Medical Center, Stanford, California

    James Ford M.D. & George Fisher M.D., Ph.D.

  2. Department of Surgery, Division of Gastrointestinal Surgery, Stanford University Medical Center, Stanford, California

    Peter S. Edelstein M.D., Mark Vierra M.D. & Augusto J. Bastidas M.D.

  3. Department of Medicine, Division of Gastroenterology, Stanford University Medical Center, Stanford, California

    Harvey Young M.D.

  4. Department of Radiation Oncology, Stanford University Medical Center, 300 Pasteur Drive, 94305, Stanford, California

    Vivek K. Mehta M.D. & Joseph Poem M.D.

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  1. Vivek K. Mehta M.D.
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  2. Joseph Poem M.D.
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  3. James Ford M.D.
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  4. Peter S. Edelstein M.D.
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  5. Mark Vierra M.D.
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Mehta, V.K., Poem, J., Ford, J. et al. Radiotherapy, concomitant protracted-venous-infusion 5-fluorouracil, and surgery for ultrasound-staged T3 to T4 rectal cancer. Dis Colon Rectum 44, 52–58 (2001). https://doi.org/10.1007/BF02234821

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