Advanced Resectable Rectal Cancer Research Articles

446 Poster Short-term regimen of preoperative radiotherapy plus total mesorectal excision for locoregional advanced resectable rectal cancer

446 Poster Short-term regimen of preoperative radiotherapy plus total mesorectal excision for locoregional advanced resectable rectal cancer

T-level downstaging and complete pathologic response after preoperative chemoradiation for advanced rectal cancer result in decreased recurrence and improved disease-free survival.

Preoperative chemoradiation therapy is used widely in the treatment of rectal cancer. The predictive value of response to neoadjuvant remains uncertain. We retrospectively evaluated the impact of response to preoperative and, specifically, of T-level downstaging, nodal downstaging, and complete pathologic response after chemoradiation therapy on oncologic outcome of patients with locally advanced rectal cancer. There were 88 patients with ultrasound Stage T3/T4 midrectal (n = 37) and low rectal (n = 51) cancers (63 males; mean age 62.6 years). All patients were treated by preoperative 5-fluorouracil-based chemotherapy and pelvic radiation followed by surgical resection in six weeks or longer (56 sphincter-preserving resections). T-level downstaging after neoadjuvant treatment was demonstrated in 36 (41 percent) of 88 patients, and complete pathologic response was observed in 16 (18 percent) of the 88. Of the 42 patients with ultrasound-positive nodes, 27 had no evidence of nodal involvement on pathologic evaluation (64 percent). The overall response rate (T-level downstaging or nodal downstaging) was 51 percent. At a median follow-up of 33 months, 86.4 percent of patients were alive. The overall recurrence rate was 10.2 percent (three patients had local and six had metastatic recurrences). Patients with T-level downstaging and complete pathologic response were characterized by significantly better disease-free survival (P = 0.03, P = 0.04) and better overall survival (P = 0.07, P = 0.08), according to Wilcoxon's test comparing Kaplan-Meier survival curves. None of the patients with complete pathologic response developed recurrence or died during the follow-up period. T-level downstaging and complete pathologic response after preoperative chemoradiation therapy followed by definitive surgical resection for advanced rectal cancer resulted in decreased recurrence and improved disease-free survival. Advanced rectal cancers that undergo T-level downstaging and complete pathologic response after chemoradiation therapy may represent subgroups that are characterized by better biologic behavior.

Preoperative concurrent radiochemotherapy for cancer of the rectum

To evaluate retrospectively treatment-related morbidity of concurrent radiotherapy and chemotherapy for rectal cancer. Between 1992 and 1995, 38 patients (median age: 60) were treated for locally advanced resectable rectal cancer. Median dose of radiotherapy was 45 Gy/25 fractions/5 weeks. Chemotherapy consisted of two courses of 5-fluorouracil and leucovorin administered during the first and the fifth weeks of radiotherapy. Median dose of 5-fluorouracil was 350 mg/m2/day, and median dose of leucovorin was 20 mg/m2/day, day 1 to day 5. Surgery was performed 5 weeks after completion of radiotherapy. Before surgery, one patient died of febrile neutropenia and sepsis after two cycles of chemotherapy and 45 Gy. Main pre-operative grade 3-4 toxicities were respectively: neutropenia: 3%; nausea/vomiting: 3%; diarrhea: 3%; proctitis: 5%; radiation dermatitis: 8%. Twenty-six patients underwent a low anterior resection and 11 an abdomino-perineal resection. A temporary colostomy was performed in 12 patients. Pathologic complete response rate was 27%. There was one post-operative death due to thromboembolic disease. Major post-operative grade 3-4 complications were: pelvic infection: 14%; abdominal infection: 5%; perineal sepsis: 8%; anastomotic dehiscence: 8%; cardiac failure: 5%. Delayed perineal wound healing was observed in six patients. No significant prognosic factor of post-operative complications has been observed. Median duration of hospitalization was 22 days. With a median follow-up of 24 months, 2-year overall and disease-free survival rates were 82 and 64%. Tolerance of preoperative concurrent chemoradiotherapy was acceptable. Ongoing controlled studies will assess the impact of this combined treatment on survival.

147 O - Effect of preoperative hyperthermia with radio-chemo-therapy on resectability of locally advanced rectal cancer. A phase II clinical

In locally advanced rectal cancer pre-operative radio-chemotherapy can increase resectability and may provide local control in unresectable cases, but response rates are still unsatisfactory. In a phase II study we investigated whether regional hyperthemia in combination with preoperative radio-chemo-therapy (HRCT) is feasible and will result in downstaging as well as improve resectability. 18 patients (pts) with primary non resectable rectal cancer entered the trial. Initial tumor stage was assessed by endorectal ultrasound (EU) and computed tomography (CT). Pre-operative treatment consisted of 5-FU (300–500 mg/m 2 , dose escalation) and leucovorin (50mg) on days 1–5 and 22–28. Regional hyperthermia (RHT) was carried out using the SIGMA 60 applicaton BSD 2000 once a week prior to radiotherapy. Radiotherapy was applied in prone position using a belly board, three-field technique, standard blocks, 5×1,8 Gy up to 45 Gy. Re-staging was carried out using EU and CT. Four weeks after HRCT, surgery was performed. Treatment-related adverse events were observed in 3 pts with grade III gastrointestinal toxicity requiring a short hospitalisation because of dehydration and/or abdominal discomfort. One patient developed grad IV toxicity with haemorrhagic enterocolitis and treatment was stopped. After treatment 14/18 pts (78%) proved resectable (R0 n = 11/R2 n = 3; Abdomino-perineal resection n = 5 and sphincter saving surgery n = 9). Nonresectable disease after explorative laparotomy was found in 4/18pts in 5 of 18 pts (27%) postoperative complications were observed with anastomatic leakage (n = 2) and perineal abscess (n = 3). A complete histological remission (pCR) was confirmed in 2/18 pts (11%). In median follow up of 13 months (rang 3–21 months) all but one R0-resected pts (n = 11) had no evidence of tumor recurrence. The patients with non-resectable carcinomas (n = 4) had a progression free survival with the range of 5–28 months. Preoperative HRCT in fessible and effective in primary non resectable rectal cancer resulting in a resectability rate of 78% with pCR in 11% of the patients. Treatment related toxicity and postoperative complication-rate are acceptable. Our results suggest that RHT in addition to radio-chemotherapy can improve treatment results in rectal cancer. Therefore a randomized phase III- study has been initiated to validate the effects of HRCT in locally advanced non resectable rectal cancer.