Preoperative Multimodality Therapy Improves Disease-Free Survival in Patients With Carcinoma of the Rectum: NSABP R-03

Abstract

A B S T R A C T PurposeAlthough chemoradiotherapy plus resection is considered standard treatment for operable rectal carcinoma, the optimal time to administer this therapy is not clear. The NSABP R-03 (National Surgical Adjuvant Breast and Bowel Project R-03) trial compared neoadjuvant versus adjuvant chemoradiotherapy in the treatment of locally advanced rectal carcinoma. Patients and MethodsPatients with clinical T3 or T4 or node-positive rectal cancer were randomly assigned to preoperative or postoperative chemoradiotherapy. Chemotherapy consisted of fluorouracil and leucovorin with 45 Gy in 25 fractions with a 5.40-Gy boost within the original margins of treatment. In the preoperative group, surgery was performed within 8 weeks after completion of radiotherapy. In the postoperative group, chemotherapy began after recovery from surgery but no later than 4 weeks after surgery. The primary end points were disease-free survival (DFS) and overall survival (OS). ResultsFrom August 1993 to June 1999, 267 patients were randomly assigned to NSABP R-03. The intended sample size was 900 patients. Excluding 11 ineligible and two eligible patients without follow-up data, the analysis used data on 123 patients randomly assigned to preoperative and 131 to postoperative chemoradiotherapy. Surviving patients were observed for a median of 8.4 years. The 5-year DFS for preoperative patients was 64.7% v 53.4% for postoperative patients (P ϭ .011). The 5-year OS for preoperative patients was 74.5% v 65.6% for postoperative patients (P ϭ .065). A complete pathologic response was achieved in 15% of preoperative patients. No preoperative patient with a complete pathologic response has had a recurrence. ConclusionPreoperative chemoradiotherapy, compared with postoperative chemoradiotherapy, significantly improved DFS and showed a trend toward improved OS.

The impact of radiation therapy sequencing on survival and cardiopulmonary mortality in the combined modality treatment of patients with esophageal cancer

“…8,9 It is postulated that preoperative treatment is favored because of tumor downstaging and smaller radiation treatment fields. We hypothesized that preoperative RT is associated with decreased cardiopulmonary mortality from lower RT doses to the heart and lungs as well as improved survival outcomes compared with postoperative RT in patients with esophageal cancer.…”

Neoadjuvant therapy for locally advanced rectal cancer

“…Тем не менее наиболее информативным методом, особенно в сочетании с иссле-дованием диффузно-взвешенных изображений (ДВИ), является МРТ. В диагностике полной регрессии опухоли специфичность МРТ+ДВИ составляет более 90%, что свидетельствует о том, что риск недооценки остаточной опухоли может быть снижен до менее 10% [20]. В нашем исследовании ЛТ на фоне приема капецитабина или оксалиплатина+капецитабина привела к достоверному увеличению частоты полных и частичных клинических ответов опухоли по сравнению с длительной инфузией 5-ФУ (OR 3,929; 95% DI 1,900-8,121; p=0,0002).…”

Bone marrow tolerance during postoperative chemotherapy in colorectal carcinomas

“…This may explain why rates of ≥grade 3 HT (HT3) for rectal cancer patients during CRT are 10% (10) and nearly 40% during postoperative OxF therapy (5). Interestingly colon cancer patients, who do not receive prior CRT, experience similar rates of HT3 of nearly 35%, and those above the age of 70 experience rates as high as 40 % during adjuvant therapy (11).…”