Enhancing quantitative approaches for assessing community resilience.

Scholars from many different intellectual disciplines have attempted to measure, estimate, or quantify resilience. However, there is growing concern that lack of clarity on the operationalization of the concept will limit its application. In this paper, we discuss the theory, research development and quantitative approaches in ecological and community resilience. Upon noting the lack of methods that quantify the complexities of the linked human and natural aspects of community resilience, we identify several promising approaches within the ecological resilience tradition that may be useful in filling these gaps. Further, we discuss the challenges for consolidating these approaches into a more integrated perspective for managing social-ecological systems.

Creation of a gilded trap by the high economic value of the Maine lobster fishery.

Unsustainable fishing simplifies food chains and, as with aquaculture, can result in reliance on a few economically valuable species. This lack of diversity may increase risks of ecological and economic disruptions. Centuries of intense fishing have extirpated most apex predators in the Gulf of Maine (United States and Canada), effectively creating an American lobster (Homarus americanus) monoculture. Over the past 20 years, the economic diversity of marine resources harvested in Maine has declined by almost 70%. Today, over 80% of the value of Maine's fish and seafood landings is from highly abundant lobsters. Inflation-corrected income from lobsters in Maine has steadily increased by nearly 400% since 1985. Fisheries managers, policy makers, and fishers view this as a success. However, such lucrative monocultures increase the social and ecological consequences of future declines in lobsters. In southern New England, disease and stresses related to increases in ocean temperature resulted in more than a 70% decline in lobster abundance, prompting managers to propose closing that fishery. A similar collapse in Maine could fundamentally disrupt the social and economic foundation of its coast. We suggest the current success of Maine's lobster fishery is a gilded trap. Gilded traps are a type of social trap in which collective actions resulting from economically attractive opportunities outweigh concerns over associated social and ecological risks or consequences. Large financial gain creates a strong reinforcing feedback that deepens the trap. Avoiding or escaping gilded traps requires managing for increased biological and economic diversity. This is difficult to do prior to a crisis while financial incentives for maintaining the status quo are large. The long-term challenge is to shift fisheries management away from single species toward integrated social-ecological approaches that diversify local ecosystems, societies, and economies.

Results of a pooled analysis of IOERT containing multimodality treatment for locally recurrent rectal cancer: Results of 565 patients of two major treatment centres.

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.

Impact of number of nodes retrieved on outcome in patients with rectal cancer.

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.

Early evaluation of combined fluorouracil and leucovorin as a radiation enhancer for locally unresectable, residual, or recurrent gastrointestinal carcinoma. The North Central Cancer Treatment Group.

PURPOSE: To develop a tolerable regimen of fluorouracil (5-FU), low-dose leucovorin, and radiation, and to obtain an early estimate of therapeutic effectiveness. PATIENTS AND METHODS: Forty patients with locally unresectable or recurrent gastrointestinal carcinoma were studied (pancreas, n = 22; rectum and sigmoid, n = 10; gastric, n = 6; other, n = 2). Irradiation therapy was administered in 1.8-Gy fractions 5 days per week, with total doses ranging from 45 to 54 Gy. 5-FU 400 mg/m2/d plus leucovorin 20 mg/m2/d, both by rapid intravenous injection, were administered for 3 or 4 days during the first and fifth weeks of radiation. 5-FU 425 mg/m2/d plus leucovorin 20 mg/m2/d were administered for 4 days at 4 weeks following radiation and for 5 days at 9 weeks. RESULTS: Major toxicities with upper abdominal treatment were nausea, vomiting, weight loss, and leukopenia. A tolerable dosage regimen was radiation at 45 Gy with 4 days of 5-FU plus leucovorin during the first week and 3 days during the last week with postradiation chemotherapy. Major toxicities with pelvic radiation were diarrhea and leukopenia. A tolerable regimen was 54 Gy with 4 days of 5-FU plus leucovorin during the first and fifth week followed by the postradiation chemotherapy. Median survival durations for pancreatic and rectal/sigmoid carcinomas are 13 months and 31 months, respectively. Five patients have no evidence of disease from 38 to 50 months after the onset of therapy (rectal, n = 2; stomach, n = 2; pancreas, n = 1). CONCLUSION: We have developed patient-tolerable regimens for combined 5-FU plus leucovorin followed by radiation to the abdomen and to the pelvis. The favorable results observed in locally unresectable disease allow cautious optimism for possible effectiveness in the surgical adjuvant setting, a possibility currently being tested in national trials of rectal and gastric carcinoma.

Evaluation and treatment of patients receiving radiation for cancer of the rectum or sigmoid colon in the United States: results of the 1988-1989 Patterns of Care Study process survey.

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.

Adjuvant postoperative fluorouracil-modulated chemotherapy combined with pelvic radiation therapy for rectal cancer: initial results of intergroup 0114.

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.

Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control--final report of intergroup 0114.

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.

Multi-institutional trial of preoperative chemoradiotherapy in patients with potentially resectable gastric carcinoma.

PURPOSE: In the West, curative (R0) resection is achieved in approximately 50% of patients with localized gastric carcinoma, and more than 60% die of cancer following an R0 resection. A multi-institutional study of preoperative chemoradiotherapy was done to assess the R0 resection rate, pathologic complete response (pathCR) rate, safety, and survival in patients with resectable gastric carcinoma. PATIENTS AND METHODS: Operable patients with localized gastric adenocarcinoma were eligible. Staging also included a laparoscopy and endoscopic ultrasonography (EUS). Patients received up to two 28-day cycles of induction chemotherapy of fluorouracil, leucovorin, and cisplatin, followed by 45 Gy of radiation plus concurrent fluorouracil. Patients were then staged and surgery was attempted. RESULTS: Thirty-four patients were registered at three institutions. One ineligible patient was excluded. Most patients had a promixal cancer and EUST3N1 designation. Twenty-eight (85%) of 33 patients underwent surgery. The R0 resection rate was 70% and pathCR rate was 30%. A pathologic partial response (< 10% residual carcinoma in the primary) occurred in eight patients (24%). EUS T plus N and postsurgery T plus N correlation showed significant downstaging (P = <.01). The median survival time for 33 patients was 33.7 months. Patients achieving a pathCR or pathPR had a significantly longer median survival time (63.9 months) than those achieving less than pathPR (12.6 months; P =.03). There were two treatment-related deaths. CONCLUSION: Our data suggest that the three-step strategy of preoperative induction chemotherapy followed by chemoradiotherapy resulted in substantial pathologic response that resulted in durable survival time. This strategy is worthy of a direct comparison with postoperative adjuvant chemoradiotherapy.

Current issues in the treatment of colorectal cancer.

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.

The current role of radiotherapy in colorectal 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.

Surgical adjuvant therapy of rectal cancer.

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.

Intraoperative irradiation: current and future status.

Intraoperative radiation therapy (IORT) in its broadest sense refers to the delivery of irradiation at the time of an operation. This article will discusses the rationale for and results of both intraoperative electron radiation therapy and intraoperative high dose rate brachytherapy when used in conjunction with surgical exploration and resection and external beam radiation therapy and chemotherapy. Both IORT methods evolved with similar philosophies as an attempt to achieve higher effective doses of irradiation while dose limiting structures are surgically displaced.

Adenocarcinoma of the stomach: areas of failure in a re-operation series (second or symptomatic look) clinicopathologic correlation and implications for adjuvant therapy.

Following initial "curative" operative procedures for gastric carcinoma, 107 patients had planned single or multiple re-operations at the University of Minnesota. Later evidence of cancer was found in 86 patients at re-operation and/or other follow-up. Initial operative-pathologic extent of disease was correlated with incidence and patterns of failure. Distant metastasis (DM) alone was uncommon, but was found as a new component in 25.6% of the failure group. Nearly half of the peritoneal failures (PS) were localized, and when diffuse, were usually accompanied by a moderate sized local-regional failure. Local recurrence and/or regional lymph node metastasis (LF-RF) occurred as the only failure in 53.7% of the failure group if localized peritoneal failures were included, and as any component of failure in 87.8% (67.3% of the total 107 patients). Operation alone yields inadequate results for the majority of patients with gastric carcinoma. The rationale of adjuvant radiation and systemic therapy alone or in combination is discussed.

Radiation therapy for small bowel carcinoma: report of three patients and review of the literature.

The potential role of radiation therapy in the management of localized small bowel carcinoma is reviewed based upon three patients irradiated at a major referral center and seven previously reported patients in the literature. The one patient irradiated postoperatively for gross residual disease has had local-regional disease control for 1.5 years. The two patients irradiated postoperatively in an adjuvant setting are alive disease at 3.8 and 0.5 years, respectively. Patients with unresectable disease (initially or at recurrence) have fared poorly. Patterns of tumor spread are reviewed, and recommendations on irradiation dose and volume are suggested.

Extrapelvic colon--areas of failure in a reoperation series: implications for adjuvant therapy.

A total of 230 patients had planned single or multiple reoperative procedures following "curative" resection of colorectal cancer at the University of Minnesota. The site of the primary lesion was extrapelvic in 91, and later evidence of cancer was found in 58 patients (64%) at re-operation and/or other follow-up. Eight of the 58 (14%) were converted to disease-free status. Incidence and patterns of failure were correlated with initial operative-pathologic extent of disease (87 of the 91 at risk had initial tumor extension beyond the bowel wall, involved nodes or both) and comparisons were made with the previously analyzed rectal reoperation patients. While a component of local-regional failure was more common with rectal lesions (48/74 at risk, 65%), it was not uncommon with extrapelvic primaries (44/91-48%). The incidence of hematogenous metastasis (DM) was equal, but the pattern of initial DM differed (extrapelvic colon--primarily liver; rectum--liver and lung). Peritoneal seeding was a more common component of failure with the extrapelvic primaries (19/91--21% vs 3/74-4%). Since surgery alone is inadequate treatment for many patients with colon as well as rectal cancer, the rationale of adjuvant radiation and systemic therapy, alone or in combination, is discussed.

Endocavitary radiotherapy of rectal cancer.

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.

Postoperative radiation therapy for incompletely resected colorectal carcinoma.

The efficacy of high-dose post-operative radiation therapy was evaluated in 56 patients with pathologically proven or suspected residual disease after surgical resection of colon or rectal carcinoma. Patients had either microscopic or gross residual. They were treated with pelvic or abdominal irradiation to a dose of 4500 cGy followed by boost therapy to as much as 6000 to 7000 cGy if small bowel could be moved from the radiation field. Patients with microscopic residual had a local failure rate of 30% compared to 57% in those with gross residual disease. Five-year disease-free survival was 45% in patients with microscopic versus 10.6% for those with gross residual tumor. There was a trend toward a dose response curve for those with microscopic disease, but none was noted with gross residual. In view of the limited results obtained with current external beam techniques, it is recommended that newer avenues, such as high-dose preoperative therapy combined with intraoperative radiation, be investigated in this poor prognosis group.

External radiation therapy and transcatheter iridium in the treatment of extrahepatic bile duct carcinoma.

PURPOSE/OBJECTIVE: Review survival, prognostic factors, and patterns of failure in patients with extrahepatic bile duct (EHBD) carcinoma treated with external beam irradiation (EBRT) and transcatheter iridium. METHODS AND MATERIALS: The charts of 24 patients with EHBD cancer treated with EBRT and transcatheter boost were reviewed. All patients had transhepatic biliary tubes or endoprostheses placed. Two patients underwent hemihepatectomy with hepaticojejunostomy formation but had residual disease. Two patients had biopsy proven adenopathy. Five patients had Grade 1 adenocarcinoma, nine Grade 2, six Grade 3, and one Grade 4 disease. Median EBRT dose was 50.4 Gy delivered in 1.8 Gy/day fractions. Median transcatheter boost at 1 cm radius was 20 Gy. Nine patients received concomitant 5-Fluorouracil (5-FU) during EBRT. RESULTS: Median survival was 12.8 months (range 7.5 months to 9 years). Overall 2- and 5-year survival rates were 18.8 and 14.1%, respectively (three disease-free survivors > or =5 years). One patient is still alive without relapse 10 years from diagnosis and 5 years after liver transplantation for liver failure (no cancer in specimen, underlying sclerosing cholangitis). Two additional long-term survivors had no evidence of relapse 6.9 and 8.2 years after diagnosis. Histologic grade, lymph node status, cystic, hepatic, common hepatic or common bile duct involvement, surgical resection, radiation therapy dose, and chemotherapy did not significantly effect survival due to the number of patients analyzed. There was a trend towards improved survival with the addition of 5-FU chemotherapy (5-year survival in two of nine patients, or 22%). Eight of 24 patients (33%) demonstrated radiographic evidence of local recurrence. Distant metastases developed in 6 of 24 (25%) patients. The most common complications were tube related cholangitis (50%) and gastric/duodenal ulceration or bleeding (42%). CONCLUSION: External beam irradiation combined with a transcatheter boost can result in long-term survival of patients with EHBD cancer. Both distant metastases and local recurrence develop in 25-30% of patients despite irradiation. Survival may be improved by using chemotherapy in combination with EBRT to impact disease relapse (local and distant). Because there may be a dose response with irradiation, survival may also be improved by increasing the dose of radiation delivered by transcatheter boost. A Phase II trial is being developed using a combination of 45-50 Gy EBRT with concomitant 5-FU delivered by protracted venous infusion followed by a 25-30 Gy transcatheter boost.

The treatment of locally advanced colon cancer.

PURPOSE: The results of therapy for 103 patients with locally advanced colon cancer who received radiotherapy were analyzed to determine the outcome and tolerance of therapy. METHODS AND MATERIALS: Between 1974 and 1994, 103 patients received radiotherapy and maximal resection of locally advanced colon cancers. Following resection, 50 patients had no residual disease, 18 patients had microscopic residual disease, and 35 patients had gross residual disease. External beam radiotherapy was initiated 1 to 4 months following resection except in two patients who received preoperative radiotherapy. Treatment was delivered to the tumor bed and adjacent lymph nodes using 4 to 18 MV X-rays with doses ranging from 16.2 to 60 Gy. Intraoperative electron radiotherapy (IOERT) was also administered to 11 of the patients with doses ranging from 10 to 20 Gy. Chemotherapy was administered to 77 patients. Follow-up in survivors ranged from 0.5 to 17 years (median: 5.8 years). RESULTS: The 5-year actuarial local failure rate was 10% for patients with no residual disease, 54% for patients with microscopic residual disease, and 79% for patients with gross residual disease (p < 0.0001). For patients with residual disease, local failure occurred in 11% of patients receiving IOERT compared with 82% of patients receiving only external beam therapy (p = 0.02). The 5-year actuarial survival rate was 66% for patients with no residual disease, 47% for patients with microscopic residual disease, and 23% for patients with gross residual disease (p = 0.0009). The 5-year survival rate in patients with residual disease was 76% for patients receiving IOERT and 26% for patients receiving external beam therapy alone (p = 0.04). CONCLUSIONS: Patients with locally advanced colon cancer who have had a complete resection have a high probability of local control after external beam irradiation +/- 5 fluorouracil (5FU)-based systemic therapy. The toxicity of therapy can be minimized with attention to treatment technique and dose. Local control and survival rates in patients with residual disease who received IOERT appear to be significantly greater than for those patients who received external beam radiotherapy therapy alone.