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.

Intraoperative radiotherapy for treatment of locally advanced and recurrent esophageal and gastric adenocarcinomas.

Intraoperative radiotherapy (IORT) allows delivery of radiotherapy doses in excess of those typically deliverable with conventional external beam radiotherapy. IORT has potential utility in clinical situations, such as treatment of esophageal and gastric malignancies, in which the radiation tolerance of normal organs limits the dose that can be given with conventional radiotherapy techniques. We reviewed the records of 50 patients who received IORT for locally advanced primary or recurrent gastric or esophageal adenocarcinomas deemed unresectable for cure. IORT was given as a single fraction of electron beam radiotherapy (10-25 Gy) after maximal tumor resection: R0 in 42%, R1 in 46%, and R2 in 12%. Forty-eight patients also received external beam radiotherapy (8-55 Gy), 46 received radiosensitizing chemotherapy, and nine received systemic chemotherapy after radiotherapy. Outcomes were estimated with Kaplan-Meier analysis. Median survival was 1.6 years. Overall survival at 1, 2, and 3 years was 70%, 40%, and 27%. Of 42 patients who died, 37 died from cancer progression and three from multifactorial treatment toxicity. Median survival for patients with recurrent disease versus primary disease was 3.0 years versus 1.3 years (P < 0.05), with a delay of metastatic failure in patients with recurrent tumors (P = 0.06). At 3 years, distant metastatic failure was 79%, local failure was 10%, and regional failure was 15%. IORT for locally advanced primary or recurrent gastric malignancies effectively decreases the risk of local failure. For patients with isolated local recurrences, IORT may be effective salvage therapy. However, more effective systemic therapy is needed as a component of treatment.

Sphincter-preserving radiation therapy for rectal cancer: a simulation study using three-dimensional computerized technology.

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.

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.

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.

Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction.

BACKGROUND: Surgical resection of adenocarcinoma of the stomach is curative in less than 40 percent of cases. We investigated the effect of surgery plus postoperative (adjuvant) chemoradiotherapy on the survival of patients with resectable adenocarcinoma of the stomach or gastroesophageal junction. METHODS: A total of 556 patients with resected adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to surgery plus postoperative chemoradiotherapy or surgery alone. The adjuvant treatment consisted of 425 mg of fluorouracil per square meter of body-surface area per day, plus 20 mg of leucovorin per square meter per day, for five days, followed by 4500 cGy of radiation at 180 cGy per day, given five days per week for five weeks, with modified doses of fluorouracil and leucovorin on the first four and the last three days of radiotherapy. One month after the completion of radiotherapy, two five-day cycles of fluorouracil (425 mg per square meter per day) plus leucovorin (20 mg per square meter per day) were given one month apart. RESULTS: The median overall survival in the surgery-only group was 27 months, as compared with 36 months in the chemoradiotherapy group; the hazard ratio for death was 1.35 (95 percent confidence interval, 1.09 to 1.66; P=0.005). The hazard ratio for relapse was 1.52 (95 percent confidence interval, 1.23 to 1.86; P<0.001). Three patients (1 percent) died from toxic effects of the chemoradiotherapy; grade 3 toxic effects occurred in 41 percent of the patients in the chemoradiotherapy group, and grade 4 toxic effects occurred in 32 percent. CONCLUSIONS: Postoperative chemoradiotherapy should be considered for all patients at high risk for recurrence of adenocarcinoma of the stomach or gastroesophageal junction who have undergone curative resection.

Treatment of cholangiocarcinoma complicating primary sclerosing cholangitis: the Mayo Clinic experience.

OBJECTIVES: The aims of this retrospective study were to assess the frequency with which we used different treatment modalities for patients with primary sclerosing cholangitis (PSC) and cholangiocellular carcinoma (CCA). METHODS: A total of 41 patients with known CCA complicating PSC with a median age of 49 yr (range, 27-75 yr) were identified from a group of 1009 patients (4%) with PSC seen over 10 yr at the Mayo Clinic. RESULTS: These patients received mainly five forms of treatment: 10 patients were treated with radiation therapy (RT) with or without 5-fluorouracil (5-FU) (seven with palliative and three with curative intent), nine with stent placement for cholestasis, 12 with conservative treatment, four with surgical resection (one of four received RT and 5-FU), and three patients with orthotopic liver transplantation and RT, with or without 5-FU. One patient was treated with 5-FU alone, one with photodynamic therapy, and one patient with somatostatin analog. A total of 36 patients died, whereas four (10%) patients survived (two with surgical resection, one with orthotopic liver transplantation and RT, and one with stent placement) during a median follow-up of 5.5 months (range, 1-75 months). One patient was lost to follow-up. CONCLUSIONS: In highly selective cases, resective surgery seems to be of benefit in PSC patients with CCA. However, these therapies are rarely applied to these patients because of the advanced nature of the disease at the time of diagnosis. Efforts should be directed at earlier identification of potential surgical candidates.

Intraoperative irradiation for locally recurrent colorectal cancer in previously irradiated patients.

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.

Prolonged disease-free survival after orthotopic liver transplantation plus adjuvant chemoirradiation for cholangiocarcinoma.

Orthotopic liver transplantation (OLT) alone for unresectable cholangiocarcinoma is often associated with early disease relapse and limited survival. Because of these discouraging results, most programs have abandoned OLT for cholangiocarcinoma. However, a small percentage of patients have achieved prolonged survival after OLT, suggesting that adjuvant approaches could perhaps improve the survival outcome. Based on these concepts, a protocol was developed at the Mayo Clinic using preoperative irradiation and chemotherapy for patients with cholangiocarcinoma. We report our initial results with this pilot experience. Patients with unresectable cholangiocarcinoma above the cystic duct without intrahepatic or extrahepatic metastases were eligible. Patients initially received external-beam irradiation plus bolus fluorouracil (5-FU), followed by brachytherapy with iridium and concomitant protracted venous infusion of 5-FU. 5-FU was then administered continuously through an ambulatory infusion pump until OLT. After irradiation, patients underwent an exploratory laparotomy to exclude metastatic disease. To date, 19 patients have been enrolled onto the study and have been treated with irradiation. Eight patients did not go on to OLT because of the presence of metastasis at the time of exploratory laparotomy (n = 6), subsequent development of malignant ascites (n = 1), or death from intrahepatic biliary sepsis (n = 1). Eleven patients completed the protocol with successful OLT. Except for 1 patient, all had early-stage disease (stages I and II) in the explanted liver. All patients who underwent OLT are alive, 3 patients are at risk at 12 months or less, and the remaining 8 patients have a median follow-up of 44 months (range, 17 to 83 months; 7 of 9 patients > 36 months). Only 1 patient developed tumor relapse. OLT in combination with preoperative irradiation and chemotherapy is associated with prolonged disease-free and overall survival in highly selected patients with early-stage cholangiocarcinoma.

Sacropelvic resection for recurrent anorectal cancer. A multidisciplinary approach.

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.

Results of irradiation or chemoirradiation following resection of gastric adenocarcinoma.

PURPOSE: To evaluate the results of postoperative irradiation +/- chemotherapy for carcinoma of the stomach and gastroesophageal junction. METHODS AND MATERIALS: The records of 63 patients who underwent resection for stomach cancer were retrospectively reviewed. Twenty-five patients had complete resection with no residual disease but with high-risk factors for relapse. Twenty-eight had microscopic residual and 10 had gross residual disease. Doses of irradiation ranged from 39.6 to 59.4 Gy with a median dose of 50.4 Gy in 1.8 Gy fractions. Fifty-three of the 63 (84%) patients received 5-fluorouracil (5-FU)-based chemotherapy. RESULTS: The median duration of survival was 19.3 months for patients with no residual disease, 16.7 months for those with microscopic residual disease, and 9.2 months for those with gross residual disease (p = 0.01). The amount of residual disease also significantly impacted locoregional control (p = 0.04). Patients with linitis plastica did significantly worse in terms of survival, locoregional control, and distant control than those without linitis plastica. The use of 4 or more irradiation fields was associated with a significant decrease in the rate of Grade 4 or 5 toxicity when compared to the patients treated with 2 fields (p = 0.05). CONCLUSIONS: There was a significant association between survival and extent of residual disease after resection as well as the presence of linitis plastica. Distant failures are common and effective systemic therapy will be necessary to improve outcome. The toxicity of combined modality treatment appears to be reduced by using greater than 2 irradiation fields.

Results of irradiation or chemoirradiation for primary unresectable, locally recurrent, or grossly incomplete resection of gastric adenocarcinoma.

OBJECTIVE: To evaluate the results of irradiation +/- chemotherapy for patients with unresectable gastric carcinoma. MATERIALS AND METHODS: The records of 60 patients with a gastric or gastroesophageal junction adenocarcinoma and a locally advanced unresectable primary (n = 28), a local or regional recurrence (n = 21), or gross residual disease following incomplete resection (n = 11) were retrospectively reviewed. Patients were treated with external beam irradiation (EBRT) alone or external beam plus intraoperative irradiation (IOERT), and 55 of the 60 (92%) patients received 5-FU based chemotherapy. RESULTS: The median survival for the entire cohort was 11.6 months. There was no significant difference in median survival between each of the three treatment groups. In examining the extent of disease there was a significant difference in survival based on the number of sites involved. Nine patients with disease limited to a single non-nodal site appeared to represent a favorable subgroup compared to the rest of the patients (median survival of 21.8 months vs. 10.2 months,p = 0.03). In the patients with recurrent disease, the number of sites involved (p = 0.05), and total dose adding external beam dose to IOERT dose (> 54 Gy vs. < or =54 Gy, p = 0.06) were of borderline significance in regard to survival. CONCLUSIONS: In patients with either primary unresectable, locally or regionally recurrent, or incompletely resected gastric carcinoma, the overall survival is similar, and related to the extent of disease based on the number of regional sites involved. The patients with a single non-nodal site of disease represent a favorable subgroup and patients with recurrent disease may benefit from total irradiation doses > 54 Gy.

Outcomes of patients receiving radiation for carcinoma of the rectum. Results of the 1988-1989 patterns of care study.

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.

Conformal irradiation for hepatobiliary malignancies.

The term 'conformal irradiation' is usually used to describe the delivery of sophisticated high dose external beam irradiation (EBRT) with the aid of 3-D treatment planning and the option of both coplanar and non-coplanar beams. Data will be presented from the University of Michigan which suggest that conformal high dose EBRT (48-72.6 Gy) can be used for intrahepatic cancers, both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHCC), to potentially increase local control and survival over what would be expected with lower dose EBRT. For purpose of this discussion, the term conformal irradiation will be expanded to include other techniques which conform the high dose irradiation boost volume in close proximity to unresected tumor or positive margins of resection. Data will be presented from series which utilize transcatheter iridium and intraoperative electron irradiation (IOERT) supplements to EBRT +/- concomitant chemotherapy. Each method intensifies treatment in an attempt to improve local control and survival.

Future role of radiotherapy as a component of treatment in biliopancreatic cancers.

For resected and unresectable pancreas cancers, data will be summarized from both adjuvant and locally unresectable pancreas cancer series (EBRT +/- IOERT) to demonstrate the justification of continuing to utilize chemo-irradiation as a component of treatment. The resultant improvements in local control with combined modality treatment, however, achieve only minimal improvements in survival in view of the high incidence of abdominal relapse (liver and peritoneal). Further improvement in survival may necessitate regional approaches for chemotherapy or may await advances in gene therapy. For locally unresectable and resected but residual bile duct malignancies, chemoirradiation appears to enhance tumor control and survival. Dose intensification of both modalities may be useful in improving disease control and survival. After chemoirradiation, the addition of liver transplant, in carefully selected patients who are unresectable with standard resection, may further enhance disease control and survival over what would be expected with either approach in isolation.

Energy and applicator size and shape used in over 800 intraoperative electron beam therapy fields.

Intraoperative radiotherapy is a treatment option for some patients with locally advanced malignancies. This report updates the Mayo Clinic experience in more than 800 patients by analyzing the use of electron energy and cone size and shape by disease site between 1981 and 1996.

The incidence and clinical consequences of treatment-related bowel injury.

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.

Indications for and results of combined modality treatment of colorectal cancer.

Combined modality chemoirradiation is commonly used as a component of treatment in combination with maximum resection for both high-risk resectable and locally advanced primary or recurrent rectal cancers. With surgically resected but high-risk rectal cancers, postoperative chemoirradiation has been shown to improve both disease control (local and distant) and survival (disease-free and overall) and was recommended as standard adjuvant treatment at the 1990 National Institute of Health (NIH) Consensus Conference on Adjuvant treatment for patients with rectal and colon cancers. Subsequent intergroup trials are being conducted to help define optimal combinations of postoperative chemoirradiation for resected high-risk rectal cancers and to test sequencing issues of preoperative versus postoperative chemoirradiation. With locally unresectable primary or recurrent colorectal cancers, standard therapy with surgery, external beam irradiation (EBRT) and chemotherapy is often unsuccessful. When intraoperative electron irradiation (IOERT) is combined with standard treatment, local control and survival appear to be improved in separate analyses from the Mayo Clinic and the Massachusetts General Hospital (MGH). However, routine use of systemic therapy is also needed as a component of treatment, in view of high rates of systemic failure.

Malignant peripheral nerve sheath tumor: analysis of treatment outcome.

PURPOSE: To analyze the results of therapy for malignant peripheral nerve sheath tumor (MPNST) and to identify prognostic factors of survival, and of local and distant control of disease. METHODS AND MATERIALS: From 1975 through 1993, 134 MPNSTs were diagnosed and treated at our institution. Tumor sites included extremities in 36 (27%) cases and non-extremities in 98 (73%). Median follow-up for survivors was 53 months (range: 7-280). There were 14 tumors of histologic grade I disease (10%), 43 of grade II disease (32%), 43 of grade III disease (32%), and 32 of grade IV (24%). Seventy-three patients (54%) underwent radiation therapy (RT) as part of their initial treatment of the primary tumor, including 14 (10%) who had brachytherapy and 16 (12%) who had intraoperative electron irradiation (IOERT) as part of their radiation course. RESULTS: The 5- and 10-year survival rates were 52% and 34%, respectively. Local and distant failure rates at 5 years were both 49%. On univariate analysis, prognostic factors significantly related to survival (log-rank: p < 0.05) included tumor size, location of disease, history of neurofibromatosis type 1 (NF-1), history of prior irradiation, surgical margin status, use of IOERT or brachytherapy, disease stage, histologic grade and tumor subtype, as well as mitotic rate and the presence or absence of necrosis. On multivariate analysis, only history of prior irradiation (p = 0.023), and surgical margin status (p = 0.0044) remained significant. For local control of disease, univariate analysis showed location of disease, surgical margin status, history of NF-1, history of prior irradiation, mitotic rate, radiation dose > or = 60 Gy, and use of IOERT or brachytherapy to be significant prognostic factors. On multivariate analysis, only surgical margin status (p = 0.0024), RT dose (p = 0.021), and use of IOERT or brachytherapy (p = 0.016) remained significant. For distant control of disease, significant prognostic factors on univariate analysis included tumor size, stage, tumor grade, mitotic rate, presence or absence of necrosis, and histologic subtype. On multivariate analysis, tumor size (p = 0.0065), grade (p = 0.036), and histologic subtype (p = 0.001) remained significant. Patients with perineurial MPNSTs had a much lower rate of distant metastasis and a better overall survival as compared with other histologic subtypes. CONCLUSION: Management of patients with MPNST involves a multi-modality approach. The goal of surgery is complete resection with negative margins. Adjuvant irradiation to doses > or = 60 Gy and the inclusion of IOERT or brachytherapy are associated with improved local control of disease.