Intraoperative radiation therapy for locally advanced recurrent rectal or rectosigmoid cancer.

BACKGROUND AND PURPOSE: To update and summarize the experience at the Massachusetts General Hospital of a treatment program of high-dose preoperative irradiation, surgical re-resection, and intraoperative radiation therapy (IORT) as a salvage treatment for patients with recurrent rectal or rectosigmoid carcinoma. PATIENTS AND METHODS: From June 1978 to February 1997, the records of 69 patients with locally recurrent rectal carcinomas or rectosigmoid carcinomas without metastases referred for consideration of IORT were reviewed. Forty-nine patients received IORT and local control and disease-free survival curves were calculated using the actuarial method of Kaplan-Meier. RESULTS: The 5-year overall survival, local control and disease-free survival rates of 49 patients receiving IORT were 27, 35, and 20%, respectively. Thirty-four patients who underwent a macroscopic complete resection had a significantly better 5-year overall survival than the remaining 15 patients with gross residual disease (33 vs. 13%, P=0.05, log rank). For those patients, local control and disease-free survival rates were 46 and 27%, respectively. Patients with a microscopic complete resection had a superior 5-year overall survival than partially resected patients (40 vs. 14%, P=0.0001, log rank). Chemotherapy had no significant influence on overall or disease-free survival. CONCLUSION: The current analysis shows the importance of a microscopic complete resection in a multi-modality approach with IORT for survival and local control. Salvage is rare for patients undergoing subtotal resection.

Does postoperative irradiation play a role in the adjuvant therapy of stage T4 colon cancer?

PURPOSE: This study analyzes the long-term outcome of patients with stage T4 colon cancer who receive postoperative irradiation. The purpose of the study is to define the potential role of this modality with current systemic therapies. PATIENTS AND METHODS: A retrospective analysis was performed of 152 patients undergoing resection of T4 colon cancer followed by moderate- to high-dose postoperative tumor bed irradiation with and without 5-fluorouracil-based chemotherapy. Of the 152 patients, 110 patients (T4N0 or T4N+) were treated adjuvantly, whereas 42 patients received irradiation for the control of gross or microscopic residual local tumor. RESULTS: For 79 adjuvantly treated patients with stage T4N0 or T4N+ cancer with one lymph node metastasis, the 10-year actuarial rates of local control and recurrence-free survival were 88% and 58%, respectively. Results were less satisfactory for patients with more extensive nodal involvement. The 10-year actuarial rates of local control and recurrence-free survival of 39 patients with T4 tumors complicated by perforation or fistulas were 81% and 53%, respectively. For 42 patients with incompletely resected tumors, the 10-year actuarial recurrence-free survival was 19%. CONCLUSIONS: In comparison with historical controls, postoperative tumor bed irradiation improves local control for some subsets of patients. In addition to standard 5-fluorouracil-based chemotherapy, adjuvant tumor bed irradiation should be considered when colon cancers invade adjoining structures, when they are complicated by perforation or fistulas, or when they are incompletely excised at the primary site.

The impact of 5-fluorouracil and intraoperative electron beam radiation therapy on the outcome of patients with locally advanced primary rectal and rectosigmoid cancer.

OBJECTIVE: To analyze the effects of 5-fluorouracil (5-FU) chemotherapy combined with preoperative irradiation and the role of intraoperative electron beam irradiation (IOERT) on the outcome of patients with primary locally advanced rectal or rectosigmoid cancer. METHODS: From 1978 to 1996, 145 patients with locally advanced rectal cancer underwent moderate- to high-dose preoperative irradiation followed by surgical resection. Ninety-three patients received 5-FU as a bolus for 3 days during the first and last weeks of radiation therapy (84 patients) or as a continuous infusion throughout irradiation (9 patients). At surgery, IOERT was administered to the surgical bed of 73 patients with persistent tumor adherence or residual disease in the pelvis. RESULTS: No differences in sphincter preservation, pathologic downstaging, or resectability rates were observed by 5-FU use. However, there were statistically significant improvements in 5-year actuarial local control and disease-specific survival in patients receiving 5-FU during irradiation compared with patients undergoing irradiation without 5-FU. For the 73 patients selected to receive IOERT, local control and disease-specific survival correlated with resection extent. For the 45 patients undergoing complete resection and IOERT, the 5-year actuarial local control and disease-specific survival were 89% and 63%, respectively. These figures were 65% and 32%, respectively, for the 28 patients undergoing IOERT for residual disease. The overall 5-year actuarial complication rate was 11%. CONCLUSIONS: Treatment strategies using 5-FU during irradiation and IOERT for patients with locally advanced rectal cancer are beneficial and well tolerated.

Sphincter preservation in rectal cancer. Local excision followed by postoperative radiation therapy.

The management of distal rectal cancer is in evolution. Although abdominoperineal resection has been long regarded as the definitive treatment of distal rectal cancer, it is associated with significant morbidity--loss of anorectal function with a permanent colostomy and a high incidence of sexual and genitourinary dysfunction. To overcome these limitations, innovative efforts are underway studying the feasibility and efficacy of a variety of sphincter-preserving operations, usually in combination with radiation therapy and chemotherapy. Local excision procedures with adjuvant therapy represent one such treatment strategy that attempts to optimize local control and survival with preservation of sphincter integrity. This article summarizes the current role of local excision and postoperative irradiation and chemotherapy for patients with carcinoma of the rectum.

Appendiceal carcinoma: patterns of failure following surgery and implications for adjuvant therapy.

BACKGROUND AND OBJECTIVES: Primary adenocarcinoma of the appendix is rare, which makes an understanding of its natural history difficult. To date, it is treated predominantly with surgery alone. This review aims to elucidate the patterns of failure and treatment outcomes when adjuvant treatment is given after primary surgical resection. METHODS: Twenty-three patients were treated with either surgery alone, or with surgery and adjuvant radiation +/- chemotherapy. A review of the clinical course of these patients was undertaken with an analysis of the local control, distant failure, disease-free survival, and overall survival. RESULTS: Most patients presented with local invasion or metastatic disease often involving the peritoneum. Overall survival was 32%, similar to the results of other studies. Analysis of patients with locally advanced disease showed improvement in overall survival and local control with postoperative radiation therapy compared to surgery alone. CONCLUSIONS: Adenocarcinoma of the appendix is a rare disease that presents most often in an advanced stage. It has been shown by others that a right hemicolectomy provides the best outcome with respect to surgical procedure. Postoperative irradiation appears to provide a benefit for both local control and overall survival.

Postoperative radiation therapy for high-risk colon carcinoma.

PURPOSE: This study examines the experience of patients treated with postoperative radiation therapy after resection of high-risk colon carcinoma in an effort to assess the potential role of this modality in combination with current systemic therapies. PATIENTS AND METHODS: From 1976 to 1989, 203 patients received postoperative radiation therapy with and without concurrent fluorouracil (5-FU) chemotherapy following resection of modified Astler-Coller B2, B3, C2, and C3 colon tumors. Of the 203 patients, 30 (15%) were identified as having residual local tumor after subtotal resection, whereas 173 (85%) had no known residual disease. The 173 patients treated with adjuvant radiation therapy were compared with a historical control group of 395 patients undergoing surgery only. RESULTS: Three groups of patients who appeared to benefit from postoperative radiation were identified. Improved local control and recurrence-free survival rates were seen for patients with stage B3 and C3 colon carcinoma treated with postoperative radiation therapy compared with a similarly staged group of patients undergoing surgery only. Irradiated patients whose tumors had an associated abscess or fistula formation had improved local control and recurrence-free survival rates compared with a similar group of patients undergoing surgery only. There appears to be a subset of patients with residual local disease after subtotal resection that may be salvaged by high-dose postoperative radiation therapy. CONCLUSION: Selected groups of patients with colon carcinoma may benefit from postoperative radiation in addition to current systemic therapies. Integration of 5-FU and levamisole with postoperative radiation therapy should be considered for patients with (1) stage B3 and C3 lesions, (2) tumors associated with abscess or fistula formation, and (3) residual local disease after subtotal resection.

Resection margins in carcinoma of the head of the pancreas. Implications for radiation therapy.

A retrospective review of the pathology and clinical course of 72 patients undergoing resection of carcinoma of the head of the pancreas was undertaken to identify the frequency of tumor involvement at standard surgical transection margins (stomach, duodenum, pancreas, and bile duct) as well as the peripancreatic soft tissue margin and the potential clinical significance of these findings. Of 72 patients undergoing resection, 37 patients (51%) were found to have tumor extension to the surgical margins. The most commonly involved margin was peripancreatic soft tissue (27 patients) followed by pancreatic transection line (14 patients) and bile duct transection line (4 patients). For 37 patients with tumor present at a resection margin, there were no survivors beyond 41 months. No difference in survival or local control was seen between 14 patients receiving postoperative radiation therapy and 5-fluorouracil (5-FU) compared with 23 patients not receiving additional treatment. In contrast, the 5-year actuarial survival and local control of 35 patients undergoing resection without tumor invasion to a resection margin was 22% and 43%, respectively. The 5-year survival and local control of 16 patients receiving adjuvant radiation therapy and 5-FU was 29% and 42%, respectively, whereas these figures were 18% and 31% for 19 patients not receiving adjuvant therapy (p > 0.10). Because residual local tumor after resection is common, preoperative radiation therapy may be beneficial in this disease. It should minimize the risk of dissemination during operative manipulation and facilitate a curative resection by promoting tumor regression. Because local failure rates approach 60% after resection and adjuvant therapy even in cases having clear resection margins, intraoperative radiation therapy to the tumor bed at the time of resection also might be considered. Protocols evaluating the feasibility and efficacy of preoperative radiation therapy and resection with intraoperative radiation therapy for patients with pancreatic cancer are underway.

Adjuvant postoperative radiation therapy for rectal adenocarcinoma.

From October 1975 to August 1988, 261 patients at high risk for local recurrence after curative resection of rectal carcinoma underwent high-dose postoperative irradiation. Patients received 45 Gy by a 4-field box usually followed by a boost to 50.4 Gy or higher when small bowel could be excluded from the reduced field. Since January 1986, patients also received 5-fluorouracil (5-FU) for 3 consecutive days during the first and last week of radiotherapy. Five-year actuarial local control and disease-free survival decreased with increasing stage of disease; patients with Stage B2 and B3 disease had local control rates of 83% and 87% and disease-free survivals of 55% and 74%, respectively. In patients with Stage C1 through C3 tumors, local control rates ranged from 76% to 23%, and disease-free survivals ranged from 62% to 10%, respectively. For patients with Stage C disease, disease-free survival decreased progressively with increasing lymph node involvement, but local control was independent of the extent of lymph node involvement. For each stage of disease, local control and disease-free survival did not correlate with the dose of pelvic irradiation. Preliminary data from this study suggest a trend toward improved local control for patients with Stage B2, C1, and C2 tumors who receive 5-FU for 3 consecutive days during the first and last weeks of irradiation compared with patients who do not receive 5-FU. Current prospective randomized studies are addressing questions regarding the optimum administration of chemotherapy with pelvic irradiation for patients following resection of rectal carcinoma.