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Objective: Aim of this study is analysing the pooled results of Intra-Operative Electron beam Radiotherapy (IOERT) containing multimodality treatment of locally recurrent rectal cancer (LRRC) of two major treatment centres., Methods and Materials: Five hundred sixty five patients with LRRC who underwent multimodality-treatment up to 2010 were studied. The preferred treatment was preoperative chemo-radiotherapy, surgery and IOERT. In uni- and multivariate analyses risk factors for local re-recurrence, distant metastasis free survival, relapse free survival, cancer-specific survival and overall survival were studied., Results: Two hundred fifty one patients (44%) underwent a radical (R0) resection. In patients who had no preoperative treatment the R0 resection rate was 26%, and this was 43% and 50% for patients who respectively received preoperative re-(chemo)-irradiation or full-course radiotherapy (p < 0.0001). After uni- and multivariate analysis it was found that all oncologic parameters were influenced by preoperative treatment and radicality of the resection. Patients who were re-irradiated had a similar outcome compared to patients, who were radiotherapy naive and could undergo full-course treatment, except the chance of local re-recurrence was higher for re-irradiated patients. Waiting-time between preoperative radiotherapy and IOERT was inversely correlated with the chance of local re-recurrence, and positively correlated with the chance of a R0 resection., Conclusions: R0 resection is the most important factor influencing oncologic parameters in treatment of LRRC. Preoperative (chemo)-radiotherapy increases the chance of achieving radical resections and improves oncologic outcomes. Short waiting-times between preoperative treatment and IOERT improves the effectiveness of IOERT to reduce the chance of a local re-recurrence., (Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: The acquisition of detailed computerized tomography (CT) imaging at the time of simulation, along with three-dimensional (3D) treatment planning software has been integrated with radiation delivery hardware to create the modality known as 3D conformal radiotherapy (3DXRT). This approach provides, in theory, a means to selectively subtract the anal sphincter from the high-dose field of irradiation in patients with stage II and III adenocarcinomas of the mid-rectum scheduled for low anterior resection (LAR)., Hypothesis: Implementation of 3DXRT with sphincter blocking may be a feasible strategy to reduce the dose of radiation distributed to the anal canal without reduction in the dose distribution to the gross tumour volume (GTV) plus adequate margins., Methods: Pretreatment simulation CT scans of 10 patients with rectal cancers located between 5 and 10 cm from the anal verge were retrieved from a computerized database. Radiation oncologists and colorectal surgeons defined the contours of the GTV and the anal sphincter, respectively, on successive CT scan slices. These contours provided the volumetric data required to quantify dose distribution and compute dose-volume histograms. The standard mode of pelvic irradiation planned with CT simulation was compared with a 'virtual CT simulation' approach, in which a sphincter block was added to the protocol., Results: The mean distance of tumours from the anal verge was 6.3 cm. In the virtual simulation treatment plan, a 2-cm margin separated the sphincter block from the lower limit of the GTV. The mean volume of the anal sphincter was 16.1 +/- 3.5 cm(3). The dose distributed to the GTV in the real plan and in the virtual simulated block plan were 51.7 +/- 1.4 and 51.6 +/- 1.4 Gy respectively (P = 0.85). By comparison the mean dose distributed to the anal sphincter was dramatically reduced by using a sphincter block (33.2 +/- 12 Gy vs 6.4 +/- 4.1 Gy, P < 0.001)., Conclusion: During a course of radiotherapy for most low- or mid-rectal cancers, the anal canal is included within the field of irradiation with a mean dose distribution to the sphincter of 33 Gy. Evaluation of 3DXRT with full sphincter block (mid-rectum) and partial sphincter block (distal rectum) is a feasible strategy to decrease the volume of anal sphincter carried to full dose without reduction in dose to the GTV. This approach, by minimizing treatment-induced damage to the anal sphincter, might improve functional outcome of LAR.

Purpose: The gastrointestinal Intergroup studied postoperative adjuvant chemotherapy and radiation therapy in patients with T3/4 and N+ rectal cancer after potentially curative surgery to try to improve chemotherapy and to determine the risk of systemic and local failure., Patients and Methods: All patients had a potentially curative surgical resection and were treated with two cycles of chemotherapy followed by chemoradiation therapy and two additional cycles of chemotherapy. Chemotherapy regimens were bolus fluorouracil (5-FU), 5-FU and leucovorin, 5-FU and levamisole, and 5-FU, leucovorin, and levamisole. Pelvic irradiation was given to a dose of 45 Gy to the whole pelvis and a boost to 50.4 to 54 Gy., Results: One thousand six hundred ninety-five patients were entered and fully assessable, with a median follow-up of 7.4 years. There was no difference in overall survival (OS) or disease-free survival (DFS) by drug regimen. DFS and OS decreased between years 5 and 7 (from 54% to 50% and 64% to 56%, respectively), although recurrence-free rates had only a small decrease. The local recurrence rate was 14% (9% in low-risk [T1 to N2+] and 18% in high-risk patients [T3N+, T4N]). Overall, 7-year survival rates were 70% and 45% for the low-risk and high-risk groups, respectively. Males had a poorer overall survival rate than females., Conclusion: There is no advantage to leucovorin- or levamisole-containing regimens over bolus 5-FU alone in the adjuvant treatment of rectal cancer when combined with irradiation. Local and distant recurrence rates are still high, especially in T3N+ and T4 patients, even with full adjuvant chemoradiation therapy.

Purpose: Information in the literature regarding salvage treatment for patients with locally recurrent colorectal cancer who have previously been treated with high or moderate dose external beam irradiation (EBRT) is scarce. A retrospective review was therefore performed in our institution to determine disease control, survival, and tolerance in patients treated aggressively with surgical resection and intraoperative electron irradiation (IOERT) +/- additional EBRT and chemotherapy., Methods and Materials: From 1981 through 1994, 51 previously irradiated patients with recurrent locally advanced colorectal cancer without evidence of distant metastatic disease were treated at Mayo Clinic Rochester with surgical resection and IOERT +/- additional EBRT. An attempt was made to achieve a gross total resection before IOERT if it could be safely accomplished. The median IOERT dose was 20 Gy (range, 10--30 Gy). Thirty-seven patients received additional EBRT either pre- or postoperatively with doses ranging from 5 to 50.4 Gy (median 25.2 Gy). Twenty patients received 5-fluorouracil +/- leucovorin during EBRT. Three patients received additional cycles of 5-fluorouracil +/- leucovorin as maintenance chemotherapy., Results: Thirty males and 21 females with a median age of 55 years (range 31--73 years) were treated. Thirty-four patients have died; the median follow-up in surviving patients is 21 months. The median, 2-yr, and 5-yr actuarial overall survivals are 23 months, 48% and 12%, respectively. The 2-yr actuarial central control (within IOERT field) is 72%. Local control at 2 years has been maintained in 60% of patients. There is a trend toward improved local control in patients who received > or =30 Gy EBRT in addition to IOERT as compared to those who received no EBRT or <30 Gy with 2-yr local control rates of 81% vs. 54%. Distant metastatic disease has developed in 25 patients, and the actuarial rate of distant progression at 2 and 4 years is 56% and 76%, respectively. Peripheral neuropathy was the main IOERT-related toxicity; 16 (32%) patients developed neuropathies (7 mild, 5 moderate, 4 severe). Ureteral narrowing or obstruction occurred in seven patients. All but one patient with neuropathy or ureter fibrosis received IOERT doses > or =20 Gy., Conclusion: Long-term local control can be obtained in a substantial proportion of patients with aggressive combined modality therapy, but long-term survival is poor due to the high rate of distant metastasis. Re-irradiation with EBRT in addition to IOERT appears to improve local control. Strategies to improve survival in these poor-risk patients may include the more routine use of conventional systemic chemotherapy or the addition of novel systemic therapies.

Purpose: We postulated that the pathologic evaluation of the lymph nodes of surgical specimens from patients with rectal cancer can have a substantial impact on time to relapse and survival., Patients and Methods: We analyzed data from 1,664 patients with T3, T4, or node-positive rectal cancer treated in a national intergroup trial of adjuvant therapy with chemotherapy and radiation therapy. Associations between the number of lymph nodes found by the pathologist in the surgical specimen and the time to relapse and survival outcomes were investigated., Results: Patients were divided into groups by nodal status and the corresponding quartiles of numbers of nodes examined. The number of nodes examined was significantly associated with time to relapse and survival among patients who were node-negative. For the first through fourth quartiles, the 5-year relapse rates were 0.37, 0.34, 0.26, and 0.19 (P: = .003), and the 5-year survival rates were 0.68, 0.73, 0.72, and 0.82 (P: = .02). No significant differences were found by quartiles among patients determined to be node-positive. We propose that observed differences are primarily related to the incorrect determination of nodal status in node-negative patients. Approximately 14 nodes need to be studied to define nodal status accurately., Conclusion: These results suggest that the pathologic assessment of lymph nodes in surgical specimens is often inaccurate and that examining greater number of nodes increases the likelihood of proper staging. Some patients who might benefit from adjuvant therapy are misclassified as node-negative due to incomplete sampling of lymph nodes.

A multimodal approach including preoperative external beam radiation, surgical resection, and intraoperative electron radiation was used in 23 patients with locally advanced anal or recurrent rectal cancers involving the sacrum. The proximal extent of complete sacral resection was S2 in three patients, S3 in 12 patients, S4 in two patients, and S5 in one patient. The tumor was confined to the anterior sacral cortex in five patients. The resection was marginal in 10, contaminated marginal in 11, and intralesional in two patients. At 19 to 54 months of followup, five patients are alive without evidence of disease and four are alive with disease. Twelve patients died of their disease, and two died of other causes. There was a mean survival of 32.9 months for the patients who were alive at followup. Kaplan-Meier survival for all patients was 82% at 1 year and 73% at 2 years, with death of disease as an endpoint. Thirteen (57%) patients had another local recurrence develop at a mean of 17.2 months. Eight (35%) patients had metastatic disease develop at a mean of 16.3 months. Proper patients selection is important in ensuring a favorable outcome from this aggressive surgery.

Background: Clinical trials of surgical adjuvant treatment for patients with rectal carcinoma (RC) indicate that postoperative radiation therapy with concurrent chemotherapy (CRT) is superior to postoperative radiation alone (RT) or surgery alone. Whether preoperative treatment is superior to postoperative treatment is controversial. This Patterns of Care Study (PCS) surveyed patients with RC treated with radiation during the years 1988-1989 to determine the national practice standards and outcomes and to compare these results with those of clinical trials., Methods: A national survey of 73 institutions was conducted using 2-stage cluster sampling, and specific information on 406 patients with RC who received radiation at 69 facilities was collected. Follow-up information on 215 patients was subsequently collected by mail survey. There were no significant differences between the known prognostic indicators or treatment-related variables for patients for whom follow-up was available compared with the variables for patients for whom follow-up was not available. Follow-up ranged from 0 to 8.44 years with a median of 4 years. One hundred fifty-four patients (71%) received postoperative treatment, either RT (37%) or CRT (34%); and 40 (18%) received preoperative treatment, either RT (15%) or CRT (3%). Ninety-six patients (45%) received chemotherapy, and for 86% of those patients chemotherapy was administered concurrently with radiation., Results: Survival was stage-dependent (85% Stage I, 69% Stage II, and 54% Stage III at 5 years, P = 0.04). Survival was also substage-dependent, and patients with C(1) cancer had significantly higher 5-year survival than those with C(2)/C(3) cancer (89% vs. 48%, P = 0.008). Local failure was similar for Stage II and Stage III patients (10% vs. 11% at 5 years, respectively). In multivariate analyses, only stage and use of chemotherapy were significant to survival (Stage III vs. Stage I and II, relative risk [RR] = 2.52, and chemotherapy vs. no chemotherapy, RR = 0.46). A significantly higher 5-year survival rate was seen with postoperative CRT than with postoperative RT (69% vs. 50%, P = 0. 011). Preoperative radiation resulted in a significantly higher 5-year survival rate than postoperative radiation (85% vs. 50%, P = 0.0006), but not compared with postoperative CRT. Survival and local failure did not differ according to radiation therapy interruption or the interval between surgery and radiation., Conclusions: Stage is an important prognostic indicator for survival, and among patients with Stage III malignancies survival in the substage C(1) is significantly higher than in the substages C(2) and C(3). As has been demonstrated in randomized trials, adjuvant postoperative CRT is superior to postoperative RT for patients with RC in this national study. These nationwide results of adjuvant treatment are comparable to those reported in randomized trials. The use of CRT was the only treatment-related factor that resulted in a significant reduction in the risk of death., (Copyright 1999 American Cancer Society.)

Objective: To assess the frequency and clinical features of treatment-induced bowel injury in rectal carcinoma patients receiving perioperative external beam radiotherapy (EBRT). The frequency of and factors associated with treatment-induced intestinal injury have previously not been well quantified for rectal cancer patients. Postoperative adjuvant chemoirradiation is recommended for Stage II and III rectal cancers, making such data of significant interest., Methods and Materials: The records of 386 consecutive patients undergoing radiotherapy with or without chemotherapy (CT) for rectal carcinoma between 1981-90 were reviewed. Eight-two patients were excluded for receiving nontherapeutic EBRT or modalities other than EBRT., Results: Symptomatic acute treatment-related enteritis (within 30 days of EBRT +/- CT) was diagnosed in 13 patients, 3 of whom developed chronic bowel injury. Chronic treatment-related enteritis was identified in 18 patients and reoperation was required in 17 (5% of the 304 patients with complete follow-up). Chronic proctitis was documented in 38 patients, including 3 patients with small bowel injury. The probability of developing treatment-induced bowel injury at 5 years following treatment was 19%. Variables associated with an increased risk of bowel injury using multivariate analysis were transanal excision (p = 0.002), escalating radiation dose (p = 0.005), and increasing age (p = 0.01). Twenty of the affected patients required operative treatment, and 2 deaths resulted from treatment-induced enteritis., Conclusion: Patients with rectal carcinoma treated with EBRT +/- CT have the risk of developing treatment-induced bowel injury. The pelvic radiation dose should be limited to < or = 5040 cGy unless small bowel can be displaced. Reperitonealization of the pelvis, or other surgical methods of excluding the small intestine should be used whenever possible.

Purpose: Locally recurrent rectal cancer is associated with poor quality of life and has justified aggressive surgical and adjuvant approaches to control the disease. This study was designed to evaluate if the use of brachytherapy in association with wide surgical excision (debulking operation) can offer reasonable palliation for patients with locally recurrent rectal cancer., Materials and Methods: Patients with biopsy-proven locally recurrent rectal cancer who were not candidates for intraoperative radiation therapy and who were previously considered as having unresectable tumors were included in the study and were followed-up from May 1981 to November 1990. All of them had undergone laparotomy and had either radical or debulking surgical resection performed. At the same time, brachytherapy was used with temporary or permanent implant of seeds of iridium-192 or iodine-125., Results: Thirty patients were included. Patients ranged in age from 28 to 74 years, and 16 patients were female. No mortality was observed, and morbidity was low (small-bowel obstruction (1 patient), intestinal fistula (1 patient), and urinary fistula (1 patient). Histologic examination of the specimen showed gross residual disease in 67 percent of patients and microscopic disease in 25 percent of patients. Long-term follow-up was possible in 28 patients. Mean follow-up and local control were, respectively, 26.5 months and 37.5 percent for gross residual disease and 34 months and 66 percent for microscopic residual disease. Eighteen patients (64 percent) had locally recurrent rectal cancer under control at the time of the last follow-up, with seven patients (25 percent) having no evidence of local or distant recurrence., Conclusion: This is the first report of brachytherapy for locally recurrent rectal cancer. This appears to offer a therapeutic alternative to patients who are not candidates for intraoperative radiation therapy. Surgical morbidity and mortality are acceptable. Local control in 18 patients (64 percent) is comparable with intraoperative radiation therapy or more morbid surgical alternatives. Cancer-related deaths are most often related to disseminated disease, which suggests the need for systemic therapy in addition to brachytherapy.

Background: Local failure rates are high for locally irresectable primary or recurrent colorectal cancer, even when chemoradiation therapy is employed., Aim: This review evaluates evidence supporting aggressive preoperative chemoradiation followed by maximal surgical resection and intraoperative radiation therapy to achieve disease control and cure for patients with locally advanced irresectable primary or recurrent rectal cancer., Results: A 5-year survival rate of 42 per cent with a central failure rate of 2 per cent may be achieved in patients with locally irresectable primary rectal cancer. In patients with locally recurrent disease, these values at 5 years are 18 and 28 per cent respectively. The 5-year incidence of distant metastasis remains high, affecting 64 per cent of patients with primary cancer and 75 per cent of those with recurrent cancer., Conclusion: A disease-free surgical resection margin remains paramount to achieve cure. Encouraging trends exist, however, for further evaluation of multimodality therapy as a means of reducing local recurrence of disease.

Purpose: The combination of radiation therapy with fluorouracil (5-FU)-based chemotherapy is generally accepted as appropriate postoperative therapy for patients with adenocarcinomas of the rectum that extend through the bowel wall or with lymph nodes positive for tumor. We attempted to determine whether the efficacy of this postoperative therapy could be improved by the addition of leucovorin and/or levamisole., Methods: A total of 1,696 patients were randomized and eligible for treatment with one of four treatment schemes. All patients received two cycles of bolus 5-FU-based systemic chemotherapy followed by pelvic radiation therapy with chemotherapy and two more cycles of the same systemic chemotherapy. Chemotherapy was either 5-FU alone, 5-FU with leucovorin, 5-FU with levamisole, or 5-FU with leucovorin and levamisole., Results: With a median follow-up duration of 48 months, there is no statistically significant advantage to any of the treatment regimens compared with bolus 5-FU alone. There is evidence of increased gastrointestinal toxicity with the three-drug combination compared with bolus 5-FU alone. Statistical analysis suggests it is very unlikely that either levamisole-containing combination will be shown to be of value with further follow-up evaluation., Conclusion: There is no evidence at present for a beneficial effect of levamisole in the adjuvant treatment of rectal cancer. Definitive evaluation of the effect of the addition of leucovorin to 5-FU and pelvic radiation will require further follow-up evaluation.

Purpose: For locally advanced primary colorectal cancer, our institution has combined intraoperative electron irradiation (IOERT) with external beam irradiation (EBRT) +/- 5-fluorouracil (5-FU) and surgical resection. Disease control and survival were compared with the current IOERT and prior non-IOERT regimens., Methods and Materials: From April 1981 through August 1995, 61 patients received an IOERT dose of 10-20 Gy, usually combined with 45-55 Gy of fractionated EBRT; 56 had minimum follow-up of 18 months. The amount of residual disease remaining at IOERT after exploration and maximal resection in the 56 patients was gross in 16, < or = microscopic in 39, and unresected in 1., Results: Survival (SR) and disease control were analyzed as a function of potential prognostic factors. Factors that achieved statistical significance for improved overall survival included treatment sequence of preop EBRT + 5-FU (vs. postoperative EBRT + 5-FU, p = 0.003) and < or = microscopic residual disease after maximal resection (vs. gross residual, p = 0.005). Those that appeared to favorably impact disease-free survival included EBRT + 5-FU (vs. EBRT alone, p = 0.01), < or = microscopic residual (vs. gross, p = 0.0014), and colon site of primary (vs. rectum, p = 0.009). Failures within an irradiation field have occurred in 4 of 16 patients (25%) who presented with gross residual after partial resection vs. 2 of 39 (5%) with < or = microscopic residual after gross total resection (p = 0.01). The significant prognostic factors for a decrease in distant metastases were the same as for disease-free SR with respective p-values of 0.013 (EBRT + 5-FU), 0.008 (microscopic residual), and 0.03 (colon primary). The current data suggests a relationship between IOERT dose and incidence of Grade 2 or 3 neuropathy (< or = 12.5 Gy--1 of 29 or 3%, > or = 15 Gy--6 of 26 or 23%, p = 0.03)., Conclusions: Both overall survival and disease control appear to be improved with the addition of IOERT to standard treatment. More routine use of systemic therapy is indicated as a component of IOERT containing treatment regimens because the incidence of distant metastases was 50% of patients at risk.

Purpose/objective: 1) Disease control and survival will be evaluated for treatment regimens containing intraoperative electron irradiation (IOERT) for locally recurrent, previously unirradiated colorectal cancers. 2) Various prognostic factors will be evaluated to determine whether they have an impact on disease control or survival., Materials and Methods: From April 1981 through August 1995, 123 patients with previously unirradiated locally recurrent colorectal cancers received IOERT at our institution, usually as a supplement to external beam irradiation (EBRT) and maximum resection. All received EBRT with or without concomitant 5-fluorouracil-based chemotherapy. Forty-five Gy in 25 fractions was given to the tumor or tumor bed plus 3-cm to 5-cm margins in 121 of 123 patients and a boost of 5.4 to 9 Gy in 3 to 5 fractions to the tumor plus 2-cm margins. Maximum resection was performed before or after EBRT. IOERT doses ranged from 10 to 20 Gy in 119 of 123 patients, with dose dependent on resection margins (130 fields in 123 patients). Maintenance chemotherapy was given to only two patients., Results: Disease relapse and survival were evaluated. Central failure (within the IOERT field) was documented in 13 of 123 patients (11 percent) with a five-year actuarial rate of 26 percent. Local relapse (in EBRT field) occurred in 24 patients (20 percent); five-year rate was 37 percent. Distant metastases occurred in 66 patients (54 percent); five-year rate was 72 percent. Median survival was 28 months, with overall survival at two, three, and five years of 62, 39, and 20 percent, respectively. Tolerance data suggest a relationship between IOERT dose and incidence of Grade 2 or 3 neuropathy (< or = 12.5 Gy, 2 of 29 or 7 percent; > or = 15 Gy, 19 of 101 or 19 percent; P = 0.12). Survival and disease control were analyzed as a function of potential prognostic factors. None of the prognostic factors had a significant impact on disease control or survival. Although there was a trend for reduction in local relapse rates with gross total vs. partial resection, this neither achieved statistical significance nor translated into improved survival. Patients with gross residual disease after maximum resection had three-year and five-year survival rates of 36 and 18 percent, respectively, which paralleled results for patients with gross total resection at 41 and 24 percent, respectively., Conclusion: Encouraging trends for improved local control with or without survival exist in separate locally recurrent colorectal IOERT analyses from our institution and other institutions. Therefore, continued evaluation of IOERT approaches seems warranted. Disease control within the IOERT and external fields is decreased when the surgeon is unable to accomplish a gross total resection. Therefore, it is reasonable to consistently add 5-fluorouracil or other dose modifiers during EBRT and to evaluate the use of dose modifiers in conjunction with IOERT (sensitizers and hyperthermia). In view of high systemic failure rates of > 50 percent in patients with locally recurrent disease, more routine use of systemic therapy is indicated as a component of IOERT-containing treatment regimens (use existent chemotherapy and/or develop effective immunotherapy and gene transfer therapy). Even with locally recurrent lesions, the aggressive multimodality approaches including IOERT have resulted in improved local control and long-term survival rates of 20 percent vs. an expected 5 percent with conventional techniques.

Purpose: Our aims were to determine the morbidity, survival and its influencing factors, and patterns of failure for patients who underwent further surgery with the hope of cure for locally recurrent rectal cancer., Methods: Between January 1981 and December 1988, 224 patients with a preoperative diagnosis of recurrent rectal cancer underwent additional surgery at Mayo Medical Center in Rochester, Minnesota. Of these, 65 underwent further surgery with the hope of cure, i.e., no gross/microscopic residual disease at tumor margins after reoperation. Factors assessed included type of original operation, time interval between operation for primary tumor and initial operation for recurrence, symptom status, degree of fixation, types of reoperations for recurrence, and adjuvant therapy., Results: None of the patients died within 30 days of reoperation. Seventeen complications requiring hospitalization and/or surgical procedure were observed in 14 patients. Extended operations (involving partial or complete removal of surrounding organs/structures) required more time to perform, a greater number of transfusions, and a longer hospital stay than more limited operations. Three-year, five-year, and median survival were 57, 34, and 44.7 months, respectively. Survival was greater after curative than after palliative resection (P < 0.001). Survival tended to be greater in females (P < 0.075) and in patients without pain (P < 0.065). Cumulative probability of local failure was 24, 41, and 47 percent at 1, 3, and 5 years, respectively. Cumulative risk of distant metastasis was 30, 51, and 62 percent at 1, 3, and 5 years, respectively., Conclusions: Our results indicate that complete excision of locally recurrent rectal cancer can provide a significant number of patients with long-term survival and can be accomplished safely in select patients.

With mobile rectal cancers, surgery alone is insufficient treatment for most patients with high-risk factors of tumour extension beyond the rectal wall, node involvement, or both in conjunction. While single modality adjuvant treatment with pre- or postoperative irradiation can reduce the incidence of local relapse, a statistically significant impact on survival has not been achieved. Combined modality postoperative chemoirradiation has resulted in both improved disease control (local and distant) and improved survival (disease free and overall). Randomized trials are underway in high-risk patients to determine the most optimal combinations of postoperative chemoirradiation and to compare preoperative versus postoperative chemoirradiation. Standard therapy with surgery, external irradiation, and chemotherapy is often unsuccessful for patients with locally advanced primary cancers that are unresectable for cure or locally recurrent cancers. When intraoperative electron irradiation is combined with standard treatment, encouraging trends are seen with regard to improvements in local control and survival in separate analyses from the Mayo Clinic and the Massachusetts General Hospital. More standard use of systemic therapy is needed as a component of treatment, however, in view of high rates of systemic failure in spite of the locally aggressive treatment regimens.

Purpose: This analysis was performed to evaluate the results of endocavitary radiotherapy (RT) administered for early rectal cancer at our institution., Methods and Materials: Patient charts were retrospectively reviewed to determine the results of endocavitary RT regarding survival, local control, and complications. Between 1987 and 1994, 25 patients were treated with endocavitary RT for early rectal cancer. Twenty had early, low grade tumors and met the criteria for treatment with curative intent. Five had more advanced, high grade, or multiple recurrent tumors and were treated with palliative intent. The tumors were treated to between 20 and 155 Gy in one to four fractions with 50 KV x-rays given through a specialized proctoscope. Patients were followed for 5 to 84 months (median = 55 months) after therapy. Local control and survival were determined using the Kaplan-Meier method., Results: Local control was achieved in 18 of the 20 patients treated with curative intent and 4 of 5 treated with palliative intent. For those patients treated with curative intent, the 5-year local control rate was 89% and the 5-year survival rate was 76%. The most significant toxicity was ulceration that occurred in 5 of the 25 patients. The ulcers were asymptomatic in three cases and associated with bleeding in one case. The fifth patient had pain. One ulcer was biopsied, resulting in perforation that was treated with an abdominal perineal resection (APR). There was no tumor found upon pathologic evaluation., Conclusions: Endocavitary RT can be used to treat patients with early, low-grade rectal cancers and will yield a high level of disease control and a low risk of serious complications. Major advantages of this treatment technique are that it requires neither general anesthesia nor hospitalization.

Purpose: To provide local control and palliation of pain, a multimodal ity approach, including external beam radiation therapy, surgical resection, and intraoperative electron irradiation (IOERT), has been used for patients with locally advanced anal or recurrent rectal cancers involving the sacrum., Methods: Sixteen consecutive patients (11 males; 5 females; ages, 44-76) underwent surgical exploration, sacrectomy, and IOERT, between 1990 and 1994., Results: Proximal extent of resection was S2-3 in four patients, S3-4 in five, and S4-5 in five. Two patients had resection of the anterior table of the sacrum. Margins were clear in 11, close in 3, and microscopically involved in 2 patients. Operative times ranged from 6 to 17 (median, 12.5) hours, and blood loss ranged from 300 to 12,600 (median, 3,350) ml. No operative deaths resulted. Major postoperative complications occurred in eight patients (50 percent): posterior wound infections and dehiscence, urinary leak, and ileal fistula. Five (31 percent) and 3 (19 percent) patients developed no or minor complications, respectively. Intensive Care Unit stay was one night for all patients, and overall hospital stay ranged from 11 to 30 (median, 16.5) days. Follow-up was available on all 16 patients. Kaplan-Meier survival was 68 percent at one year and 48 percent at two years. At the time of analysis, 9 of 16 patients were alive. Of the nine alive patients who responded to a questionnaire, eight reported a reduction in pain and improved quality of life postoperatively., Conclusions: Sacropelvic resection, in conjunction with IOERT, provides palliation and offers potential for cure in patients with locally advanced or recurrent anorectal cancer.

During the last two decades, radiotherapy has become an integral part of the multidisciplinary approach in the treatment of patients with colorectal cancer. Currently, radiotherapy is seen mainly as an adjuvant therapy, sometimes in combination with chemotherapy, in a pre- or postoperative setting. Adjuvant radiotherapy alone leads to a significant reduction of local recurrence rates, but an impact on survival is seen only in subset analyses. Combined modality treatment can reduce local recurrence rates even further, and can also reduce the rate of distant relapses and increase survival. The acute toxicity of combined modality is considerably higher. Local radiation can also be use as a component of organ conserving local treatment for selected early lesions. Radiotherapy has been an important palliative treatment modality, diminishing symptoms in cases of inoperable primary rectal cancers or pelvic recurrences. The timing of radiation, surgery and chemotherapy has been under evaluation for years. For patients with locally advanced primary or recurrent malignancies (unresectable due to fixation), the preferred sequence is pre-operative irradiation with or without chemotherapy, followed by surgical resection. For mobile resectable lesions, sequencing issues are being tested in phase III randomised trials.

Background: In patients with locally recurrent rectal cancer, long-term disease control and survival is uncommon with single-modality therapy. This report evaluates results achieved at the Mayo Clinic (Rochester, MN) with single- or combined-modality treatment, including intraoperative irradiation., Methods: From 1981 to 1988, 106 patients underwent palliative surgical resections at the Mayo Clinic for locally recurrent rectal cancer. None had evidence of extrapelvic disease, and 42 received intraoperative electron beam irradiation (IORT) as a component of treatment. Gross residual disease remained after maximal surgical resection in 34 of the 42 patients and 61 of the patients who did not receive IORT. The IORT dose was 15-20 Gy in 39 patients and 10, 25, and 30 Gy in the other 3. External beam irradiation (EBRT) was administered to 41 of the 42 patients (doses > or = 45 Gy to 38 patients)., Results: Kaplan-Meier survival estimates at 3 and 5 years were analyzed for the 106 patients. Palliative surgical resection alone (12 patients) resulted in a 3-year survival of 8% and a 5-year survival of 0%. Statistically significant factors relative to survival based on the univariate analysis of all patients included amount of residual tumor (microscopic vs. gross, P = 0.032) treatment method (P = 0.005), IORT versus no IORT (P = 0.0006), type of symptoms (P = 0.0075), type of fixation (P < 0.0001), and preoperative Eastern Cooperative Oncology Group status (P = 0.03). For patients who received IORT, 3-year survival with gross residual tumor or presentation with pain was 44% and 43%, respectively. Factors not associated with survival (univariate) included extended versus conventional surgical resection, grade, age, and sex. The 3-year cumulative probability of distant metastasis was 60% in the patients who received IORT and 54% in those who did not. The 3-year local relapse rates were 40% versus 93% in patients who received IORT versus those who did not., Conclusions: Although the addition of IORT to external irradiation and maximal surgical resection appears to improve local tumor control and survival in patients who undergo palliative surgical resection for locally recurrent rectal cancer, further gains in treatment are necessary. Considering the high rates of distant metastasis, more routine systemic therapy with 5-fluorouracil (5-FU) leucovorin, 5-FU levamisole, or all three needs to be incorporated into aggressive treatment approaches. In patients with gross residual tumor after maximum surgical resection, local tumor control is inadequate despite treatment combinations including IORT. The evaluation of radiation sensitizers or biologic modifiers during external irradiation and IORT is indicated.

Background: The combination of radiation therapy and chemotherapy with fluorouracil plus semustine after surgery has been established as an effective approach to decreasing the risk of tumor relapse and improving survival in patients with rectal cancer who are at high risk for relapse or death. We sought to determine whether the efficacy of chemotherapy could be improved by administering fluorouracil by protracted infusion throughout the duration of radiation therapy and whether the omission of semustine would reduce the toxicity and delayed complications of chemotherapy without decreasing its antitumor efficacy., Methods: Six hundred sixty patients with TNM stage II or III rectal cancer received intermittent bolus injections or protracted venous infusions of fluorouracil during postoperative radiation to the pelvis. They also received systemic chemotherapy with semustine plus fluorouracil or with fluorouracil alone in a higher dose, administered before and after the pelvic irradiation., Results: With a median follow-up of 46 months among surviving patients, patients who received a protracted infusion of fluorouracil had a significantly increased time to relapse (P = 0.01) and improved survival (P = 0.005). There was no evidence of a beneficial effect in the patients who received semustine plus fluorouracil., Conclusions: A protracted infusion of fluorouracil during pelvic irradiation improved the effect of combined-treatment postoperative adjuvant therapy in patients with high-risk rectal cancer. Semustine plus fluorouracil was not more effective than a higher dose of systemic fluorouracil given alone.

Purpose: For the first time, a Patterns of Care Study (PCS) was conducted in 1989 to determine the national practice standards of radiation oncologists in evaluating and treating adenocarcinoma of the rectum and sigmoid colon., Materials and Methods: A national survey of 73 institutions using two-stage cluster sampling was conducted, and specific information on 408 patients from 69 facilities with adenocarcinoma of the rectum and sigmoid colon who received radiation as part of definitive or adjuvant management was collected., Results: Using the modified Astler-Coller (MAC) pathologic staging system, the stage distribution was as follows: A, 0.5%; B1, 4.4%; B2, 23.5%; B3, 5.1%; C1, 8.9%; C2, 30.2%; and C3, 6.6%. Preoperative radiation was used in 29% of patients, but the total dose was greater than 40 Gy in only 20%. Seventy-three percent of patients received postoperative radiation, with approximately 4% receiving combined preoperative and postoperative radiation. Chemotherapy was administered to 44% of patients overall, representing 55% of patients with disease through the bowel wall and/or involving lymph nodes. Only 37% of all patients received chemotherapy concurrent with radiation. An abdominoperineal resection was used in 43%; a low anterior resection was used in 43% as well, while 5% underwent other types of bowel resection. Approximately 8% of patients were treated with a local curative procedure less than bowel resection (eg, local excision, endoscopic resection, fulguration, or contact radiation). At least one third of patients had interruption in their pelvic irradiation of greater than 3 days. There was no statistically significant difference in the frequency of treatment interruptions by dose per fraction or whether chemotherapy was given concurrent with radiation. There was no significant difference in total dose delivered to patients staged B2 and higher treated without chemotherapy compared with concurrent chemotherapy and radiation. Also, there was no significant difference in total dose delivered to patients with B1 and B2, or C1 and C2 versus B3 or C3 cancer., Conclusion: This study was conducted on patients treated just before the 1990 National Institutes of Health consensus guidelines issued on the management of colon and rectal cancer. This study indicates that the minority of patients treated with radiation in 1988 and 1989 received concurrent chemoradiation, as currently recommended. Additionally, insofar as present studies are investigating important issues such as the use of sphincter-sparing procedures, preoperative radiation and chemotherapy, and the importance of radiation dose and scheduling with chemotherapy, the information provided by this study will serve as a useful baseline to track future changes in rectal cancer evaluation and management.

Relapses after "curative resection" of rectal cancer may be localized and thus amenable to surgical treatment. The risk of relapse may be higher than previously believed depending on adequacy and length of follow-up, the diagnostic modalities used, and the number of autopsies performed. Technical refinements such as a distal margin greater than 2 cm, radical pelvic lymphadenectomy, and high ligation of the inferior mesenteric artery at the aorta do not appear to diminish the risk of recurrence. A wider lateral margin and a more complete excision of the mesorectum may be beneficial, but this is yet unproven. Surgery for isolated, locally recurrent lesions should be limited to carefully selected patients and performed in tertiary centers using a team approach. Whether such radical "salvage" procedures are justifiable merits further careful evaluation.

Surgical resection continues to be the primary curative modality for patients with adenocarcinoma of the rectum. However, local tumor recurrence in the pelvis and/or distant metastasis may occur in spite of complete excision of grossly visible malignant disease. Surgical and pathologic staging can identify a subset of surgically treated rectal cancer patients at high risk for tumor relapse and death. Irradiation and chemotherapy have been used as adjuvant therapy in conjunction with surgery as single modalities and in combination for patients with high risk rectal cancer. Evidence from controlled clinical trials indicates a significant decrease in local tumor recurrence, and a significant improvement in disease-free and overall survival with the use of combined postoperative irradiation and chemotherapy in this setting. A current national clinical trial in the United States of America is studying whether irradiation can be combined with new chemotherapy regimens which have shown significant therapeutic benefit as surgical adjuvant therapy for patients with high risk colon cancer (5FU + levamisole) and for patients with metastatic colorectal cancer (5FU + leucovorin) to further improve the efficacy of surgical adjuvant therapy for adenocarcinoma of the rectum.

Useful palliation can often be achieved when standard treatment approaches of external beam irradiation and chemotherapy with or without resection are used for locally advanced primary rectal malignancies. Local control and long-term survival are achieved in only 10% to 50% of patients, however, due to the limited irradiation tolerance of surrounding organs and tissues. Encouraging trends exist in separate intra-operative irradiation analyses from Massachusetts General Hospital and Mayo Clinic with regard to improvement in local control and possibly survival of locally advanced rectal lesions, warranting continued evaluation of such approaches. Disease control within the intra-operative and external irradiation field is decreased, however, when the surgeon is unable to accomplish gross total resection. Therefore it seems reasonable to consistently add 5-Fluorouracil with or without Leucovorin during external irradiation and to evaluate the use of dose modifiers, such as sensitizers or hyperthermia, in conjunction with intra-operative irradiation. Since high systemic failure rates exist with both locally advanced primary and recurrent lesions, more effective chemotherapy needs to be evaluated during external irradiation as well as after completion of such. In view of survival advantages with 5-Fluorouracil plus Leucovorin versus 5-Fluorouracil alone for metastatic disease, this regimen is currently being employed. Even with locally recurrent lesions, the aggressive multimodality approaches including intra-operative irradiation have resulted in improved local control, and long-term survival rates of 20% to 25% versus an expected 5% with conventional techniques in historical series.

Background: Radiation therapy as an adjunct to surgery for rectal cancer has been shown to reduce local recurrence but has not improved survival. In a previous study, combined radiation and chemotherapy improved survival significantly as compared with surgery alone, but not as compared with adjuvant radiation, which many regard as standard therapy. We designed a combination regimen to optimize the contribution of chemotherapy, decrease recurrence, and improve survival as compared with adjuvant radiation alone., Methods: Two hundred four patients with rectal carcinoma that was either deeply invasive or metastatic to regional lymph nodes were randomly assigned to postoperative radiation alone (4500 to 5040 cGy) or to radiation plus fluorouracil, which was both preceded and followed by a cycle of systemic therapy with fluorouracil plus semustine (methyl-CCNU)., Results: After a median follow-up of more than seven years, the combined therapy had reduced the recurrence of rectal cancer by 34 percent (P = 0.0016; 95 percent confidence interval, 12 to 50 percent). Initial local recurrence was reduced by 46 percent (P = 0.036; 95 percent confidence interval, 2 to 70 percent), and distant metastasis by 37 percent (P = 0.011; 95 percent confidence interval, 9 to 57 percent). In addition, combined therapy reduced the rate of cancer-related deaths by 36 percent (P = 0.0071; 95 percent confidence interval, 14 to 53 percent) and the overall death rate by 29 percent (P = 0.025; 95 percent confidence interval, 7 to 45 percent). Its acute toxic effects included nausea, vomiting, diarrhea, leukopenia, and thrombocytopenia. These effects were seldom severe. Severe, delayed treatment-related reactions, usually small-bowel obstruction requiring surgery, occurred in 6.7 percent of all patients receiving radiation, and the frequencies of these complications were comparable in both treatment groups., Conclusions: The combination of postoperative local therapy with radiation plus fluorouracil and systemic therapy with a fluorouracil-based regimen significantly and substantively improves the results of therapy for rectal carcinoma with a poor prognosis, as compared with postoperative radiation alone.

For irradiation of inoperable, residual or recurrent colorectal cancers, doses of 4,500 to 5,000 rads can achieve short-term palliation; doses must be increased to 6,000 to 7,000 rads or more, however, if long-term control of disease or possible cure is desired. The ability to achieve those dose levels safely depends on close interaction between the surgeon, the radiation oncologist and the diagnostic radiologist in defining and displacing normal and tumor tissues. Methods used at Massachusetts General Hospital from March 1976 to August 1979 are defined. They include the use of operative clips and pelvic reconstruction, diagnostic computed tomography and ultrasound, radiotherapy optimization including shrinking field techniques, radiation with bladder distention and single intraoperative boost doses given in combination with external beam.

A report of an innovative approach to the treatment of locally recurrent rectal cancer following abdominoperineal resection is presented. Curative doses of external beam radiation therapy could not be delivered to an area of locally recurrent cancer because of contiguous small-bowel loops. The patient received 5040 rads external beam radiation therapy, and then underwent intraoperative electron beam boost to the main tumor-bearing area. An additional 1500 rads was delivered with 23 MeV electrons. This approach can be safely applied to selected patients with residual, primarily unresectable, or locally recurrent adenocarcinoma of the rectum or rectosigmoid.

In recent years, various approaches have been used to improve survival and the quality of life in patients after surgical treatment of rectal carcinoma. These approaches include earlier detection, sphincter-saving procedures, and adjuvant therapy, intraoperative therapy for locally advanced tumors, and a more aggressive approach for locally recurrent or distal but isolated spread of the disease.

While combinations of external beam radiation (XRT) and surgery decrease pelvic recurrence and improve survival in the subgroups with residual disease (postop XRT) or initially unresectable disease (preop XRT), local recurrence is still unacceptably high, and survival could be improved. In view of this, pilot studies were instituted at Massachusetts General Hospital in which 32 patients received the standard previous treatment of external beam irradiation and surgery but in addition had an intraoperative electron beam boost of 1000-1500 rad to the remaining tumor or tumor bed. For the 16 patients who presented with unresectable primary lesions, the addition of intraoperative radiotherapy has resulted in a total absence of local recurrence with a minimum 20 month follow-up, and survival rates are statistically better than for the previous group treated with only external beam irradiation and surgical resection. In the group with residual disease, again there have not been any local recurrences in the 7 patients who received all treatment modalities versus 54% and 26% for the group with gross and microscopic residual treated with only external beam techniques. The remaining 9 patients presented with recurrent unresectable lesions--3 are alive (2 NED) at greater than or equal to 3 years.

Between 1976 and 1981, 147 patients with residual, inoperable, or locally recurrent carcinoma of the rectum were randomized to receive either radiation (XRT) alone or XRT plus chemotherapy (concomitant 5-FU during XRT and maintenance 5-FU + MeCCNU). An initial field received 4,500-5,100 rad in 5-6 weeks, with a boost field dose to a maximum of 7000 rad/8 weeks (maximum 6,000 rad/7 weeks with chemotherapy), dependent on findings of special small bowel films. One hundred twenty-nine patients were evaluable (65 XRT, 64 XRT + chemo). There were no statistically significant differences between treatments with respect to overall survival, complete remission rate, time to disease progression, local failure rate, or radiation dose distribution. Median survival was 17 months for XRT, 18 months for XRT + chemo; the 2-year survival probability was 36% for XRT, 44% for XRT + chemo. Initial performance status was a significant prognostic factor for both survival and time to disease progression. A trend was observed favoring the combination treatment for patients with residual disease. Treatment complications were greater for the combined modality arm than for radiation alone. Twenty-seven patients (22%) were alive at last data analysis, with no evidence of disease (NED) from 2-51 months (30 months median). Patients with resection of gross disease before or after irradiation had a much better result than those with gross residual or without any resection, but the relative influence of patient selection versus impact of surgery remains unclear.

For colorectal cancers that are confined to the bowel wall with uninvolved nodes, surgery alone is curative in most patients, and adjuvant treatment is usually not indicated. A combined modality approach for the initial treatment of many rectal and selected colonic carcinomas is based on data that "radical" operations do not necessarily prevent either local regrowth or distant failures and acceptance of a significant palliative but infrequent curative role for irradiation and chemotherapy when such failures occur. Published data for rectal cancer indicates that local recurrence can be markedly reduced by moderate to high dose pre- and post-operative irradiation +/- chemotherapy. For colon cancer, data from pilot trials suggest that post-operative irradiation may reduce local recurrence by stage when compared with surgery alone analyses, but randomized trials are needed. With locally advanced disease, aggressive treatment combinations appear to increase both local control and survival, but much interaction is required between involved physicians.

We have devised a single after-loading applicator, the Martinez Universal Perineal Interstitial Template (MUPIT), which has been used in combination with external beam irradiation to treat 104 patients with either locally advanced or recurrent malignancies of the cervix, vagina, female urethra, prostate, or anorectal region. Twenty-six patients treated for prostate cancer are excluded because of their short follow-up. Local failure developed in 13 of the 78 remaining patients (16.6%)--major complications developed in 4 patients (5.1%). Follow-up has been 1 year to 7 1/2 years; 60/78 patients have been followed for more than 2 years. All local recurrences and complications occurred before 18 months. The device consists of two acrylic cylinders, an acrylic template with an array of holes that serve as guides for trocars, and a cover plate. In use, the cylinders are placed in the vagina and/or rectum or both and then fastened to the template so that a fixed geometric relationship among the tumor volume, normal structures, and source placement is preserved throughout the course of the implantation. Appropriate computer programs have been developed to calculate the dose from these implants. The advantages of the system are (a) greater control of the placement of sources relative to the tumor volume and critical structures, as a result of the fixed geometry provided by the template and cylinders, and (b) improved dose-rate distributions obtained by means of computerized optimization of the source placement and strength during the planning phase. We conclude that the local control rate (83.4%) with low morbidity (5.1%) achieved with the combination of external beam irradiation and MUPIT applicator in these patients with locally advanced malignancies represents an improvement over previous published results with other applicators.

The records of 25 patients with unresectable carcinoma of the rectum and rectosigmoid who received preoperative radiation therapy (RT) were reviewed. Twenty patients were considered to be resectable following RT (80%). Sixteen patients (64%) underwent curative resections. All patients with unresectable tumors following RT died with tumor within two and one half years (median survival, 11 months). For patients undergoing curative resection, the probability of two- and five-year survival was 56% and 43%, respectively. In this latter group, five of seven patients with treatment failures (71%) had a pelvic component of disease. The incidence of pelvic recurrence was correlated with the pathologic stage, extent of resection and preoperative radiation dose. The need for more aggressive treatment for patients with these advanced tumors is emphasized. Future treatment alternatives are discussed.

Surgery is the preferred method of curative therapy for carcinoma of the rectum. However, in spite of complete gross tumor resection, many patients with locally advanced tumors will experience recurrence of malignant disease in the pelvis and/or distant metastases. This article summarizes the roles of radiotherapy and chemotherapy, administered alone and in combination, as surgical adjuvant treatment for patients with resectable rectal cancer. A biostatistical overview is presented. It is concluded that strong evidence exists supporting the efficacy of combined postoperative radiotherapy and chemotherapy. Further clinical trials are indicated to determine the optimum chemotherapy regimen, sequence, and duration of the therapy.

For colorectal cancer, the adjuvant radiation dose levels required to achieve a high incidence of local control closely parallel the radiation tolerance of small bowel (4500-5000 rad), and for patients with partially resected or unresected disease, the dose levels exceed tolerance (6000-7000 rad). Therefore, both the surgeon and the radiation oncologist should use techniques that localize tumor volumes and decrease the amount of small intestine within the irradiation field. Surgical options include pelvic reconstruction (reperitonealization, omental flaps, retroversion of uterus, etc.) and clip placement. Radiation options include the use of radiographs to define small bowel location and mobility combined with treatment techniques using multiple fields, bladder distention, shrinking or boost fields, and/or patient position changes (prone, decubitus, etc.). When both specialties interact in optimum fashion, local control can be increased with minimal risks to achieve a suitable therapeutic ratio.

The ability to demonstrate an improvement in therapeutic ratio is critical in assessing new treatment modalities; an evaluation of treatment complications is essential for this purpose. We have studied the severe complications occurring after treatment with intraoperative radiation therapy (IORT) in patients with locally advanced carcinoma of the rectum. Four groups of patients were compared: Group 1 (80 patients) had treatment with surgery alone for mobile and resectable tumors; Group 2 (23 patients) had treatment with high dose preoperative irradiation followed by surgical resection for tumors which were fixed to adjacent structures and initially unresectable for cure; Group 3 (24 patients, primary disease) and Group 4 (17 patients, locally recurrent disease) had locally advanced tumors as in Group 2 but were treated with IORT after preoperative irradiation and attempted surgical resection. All but 3 complications occurred within one year of therapy. Severe complications were seen in 16% of patients in Group 1, 35% in Group 2, 21% in Group 3 and 47% in Group 4 (32% in Groups 3 and 4 combined). There was a statistically insignificant increase (p = .10) in the complication rate in all irradiated patients (locally advanced tumors) compared to surgery alone (clinically mobile tumors). These data indicate no increase in severe complications with the use of IORT. If the ongoing studies continue to show improved local control with the use of IORT, expanded use of this modality may be warranted.

Local recurrence occurs in 30% to 50% of rectal cancer patients treated with surgery alone if there is tumor extension beyond the bowel wall alone or in conjunction with nodal involvement. This analysis is of 97 such patients who received postoperative irradiation (XRT) in prospective and standardized fashion at Massachusetts General Hospital (MGH) (4500 rad in 25 fractions to large fields and minimum dose of 5040 rad in 28 fractions within a boost field). Results were compared with a group of 103 previously analyzed patients treated with surgery alone at MGH. A statistically significant decrease in local recurrence was seen in four of the six irradiated subgroups (modified Astler-Coller Stages B2g, B3, C1 + C2m, and C2g) at an interval 3 years from resection. This improvement was achieved with no increase in small bowel complications (4% with XRT versus 5% with surgery alone) in view of efforts at surgical reconstruction and use of multiple-field XRT techniques, bladder distension, etc.

In an effort to treat the difficult problem of recurrent rectal cancer more successfully, we embarked on an aggressive therapeutic course involving a combination of field irradiation, surgical debulking, and intraoperative radiation therapy. On the basis of our study of 24 patients treated with this regimen, we estimated the local effectiveness to be as high as 85%. Prolonged survival was achieved in 67% of our patients.

Colorectal cancer recurs within the operative field in 10-20 per cent of patients undergoing potentially curative surgery. In certain subgroups, the recurrence rate is 20-50 per cent. There are some data to suggest either preoperative or postoperative radiation therapy as an adjuvant to potentially curative surgery can reduce the local operative failure rate. However, since radiation therapy has significant side effects, patient selection to maximize the therapeutic ratio is important. This report defines the criteria at the Massachusetts General Hospital for selection of patients with colorectal cancer for adjuvant radiation therapy, defines radiation therapy-surgery sequencing alternatives used, and describes techniques to reduce radiation side effects. Over a period of three and a half years, 196 patients received adjuvant radiation therapy: 51 patients received either moderate or low dose preoperative radiation therapy to rectal or rectosigmoid cancers, and 161 patients received postoperative radiation therapy to the pelvis or extrapelvic colonic tumor-lymph node beds. Some patients who received low-dose preoperative radiation therapy also received moderate-dose postoperative radiation therapy. We prefer moderate-dose postoperative radiation therapy as the approach most likely to decrease the local recurrence rate with minimal interference with surgical procedures and late small-bowel complications. Patients who received postoperative radiation therapy were those without distant metastases, whose primary tumor pathology revealed macroscopic or extensive microscopic transmural tumor penetration into extraperitoneal tissues. Careful case selection, multiple field techniques, the use of reperitonealization, omental flaps, and retroversion of the uterus into the pelvis were combined with postoperative small-bowel x-rays, bladder distention, and lateral portals to minimize radiation damage to normal structures.

Between 1977 and 1984, 17 patients received external beam irradiation after subtotal resection of rectal carcinoma. Ten patients had microscopic residual disease and 7 had gross residual disease. In the group with microscopic residual disease, 4 had tumor cut through with pathologically involved margins, 5 had adjacent unresected structures that were biopsy positive, and 1 had tumor spillage into the pelvis. The patients with gross residual disease were noted by the surgeon to have visible tumor after maximal debulking. Nine of 17 cases had involved pelvic lymph nodes. Radiation was administered to the pelvis with 4, 6, or 10 MV photons. Doses ranged from 40 to 60 Gy, with a median dose of 50 Gy given at 1.8 to 2.0 Gy per fraction, 5 days per week. Three patients received bacillus Calmette-Guérin (BCG), 2 received 5-fluorouracil (5-FU), and 1 received hycanthone. Thirteen of the 17 patients (76%) experienced local failure and, of these, 10 also developed distant disease. No patients developed distant metastasis in the absence of local failure. Local control was achieved in 3 of 10 patients (30%) with microscopic residual and 1 of 7 (14%) with gross residual. Four of the 17 patients (24%) have remained free of disease for greater than 5 years. External beam irradiation is capable of producing long-term survival and local control in a minority of patients with rectal cancer after subtotal resection. Investigation of more aggressive forms of therapy such as the addition of intraoperative irradiation, brachytherapy, radiation dose modifiers, and chemotherapy is warranted.

Computed tomography (CT) correctly identified extraluminal extension in carcinoma of the rectum and distal sigmoid in 20 patients who were deemed clinically inoperable because of tumor fixation. All patients received preoperative radiation therapy and subsequent surgical resection of the tumor. The findings at surgery corroborated the presence and location of tumor extension deep to the wall of the colon. Based on this preliminary data, further investigation into the place of CT in treatment planning of colon carcinomas is indicated.

A regimen of low-dose preoperative radiation therapy (RT), surgery, and elective postoperative RT for resectable carcinomas of the rectum and rectosigmoid is presented. Initial results in a group of 36 patients is discussed. In four patients clinically silent metastatic disease was discovered. Of 16 patients without indications for postoperative RT, only one died with disease. Indications for postoperative irradiation were found in 15 patients and four relapses (26%) subsequently occurred. Since the surgicopathologic stage of the tumor is the best prognostic predictor for rectal cancer, this regimen allows for the delivery of high-dose adjuvant irradiation only to those at high risk of local recurrence. Thus, this combination selects patients likely to benefit from postoperative RT while preserving the advantages of preoperative RT.

In view of poor local control rates obtained with standard treatment, intraoperative radiation (IORT) using electrons was combined with external beam irradiation and surgical resection, with or without 5-fluorouracil (5FU), in 51 patients with locally advanced colorectal cancer (recurrent, 36 patients; primary, 15 patients). Patients received 4500-5500 cGy (rad) of fractionated, multiple field external beam irradiation and an IORT dose of 1000-2000 cGy. Thirty of 51 patients (59%) are alive and 22 patients (43%) are free of disease. In 44 patients at risk greater than or equal to 1 year, local progression within the IORT field has occurred in 1 of 44 (2%) and within the external beam field in 8 of 44 (18%). All local failures have occurred in patients with recurrence or with gross residual after partial resection, and the risk was less in patients who received 5FU during external irradiation (1 of 11, 9% vs. 6 of 31, 19%). The incidence of distant metastases is high in patients with recurrence, but subsequent peritoneal failures are infrequent. Acute and chronic tolerance have been acceptable, but peripheral nerve appears to be a dose-limiting structure. Randomized trials are needed to determine whether potential gains with IORT are real.

Seventy-six cases of colon or anorectal cancer after pelvic irradiation for other malignant or benign lesions were reviewed. The patients were 13 men and 63 women with a mean age of 65 years; 67 percent had received irradiation for gynecologic malignancy. The cancer developed at a mean of 15.2 years after irradiation (peak frequency between five and ten years); 85 percent of the patients had a mild to prominent radiation reaction around the cancer. Of the 72 adenocarcinomas, 26 percent were mucinous. Only 17 percent of patients presented with symptoms of radiation proctitis, and the mean radiation dosages were not high. High radiation dosage and severe radiation damage may not be essential for radiation-associated colorectal cancer. The overall five-year survival rate was 48 percent. Close surveillance of the colon and anorectal regions of these high-risk patients at five years after irradiation is indicated.