Intraoperative electron-beam therapy for primary and recurrent retroperitoneal soft-tissue sarcoma

PURPOSE: This study assesses the long-term outcome of patients with retroperitoneal soft-tissue sarcomas treated by maximal resection in combination with intraoperative electron-beam therapy (IOERT) and postoperative external-beam radiotherapy. METHODS AND MATERIALS: From 1991 to 2004, 67 patients were treated with curative intent for primary (n = 26) or recurrent (n = 41) retroperitoneal soft-tissue sarcoma. All patients underwent maximal resection in combination with IOERT (mean dose, 15 Gy), 45 patients underwent additional postoperative EBRT, and 20 patients were previously irradiated. RESULTS: The 5-year actuarial overall survival (OS), disease-free survival, local control (LC), and freedom from metastatic disease of all patients was 64%, 28%, 40%, and 50%, respectively. The 5-year LC inside the IOERT field was 72%. For patients who completed IOERT and EBRT after R0-resection 5-year and 10-year OS was 80%, and 5-year and 10-year LC was 100%. Only 1 of the 21 patients after R0-resection and only 8 of 34 patients after R1-resection compared with 9 of 12 patients after R2-resection experienced inside IOERT-field relapse. Grade II or higher late complications were seen in 21% of the patients, but only 2 patients required surgical intervention because of late complications. CONCLUSION: In selected patients, IOERT results in excellent local control and survival, with acceptable morbidity.     

Intraoperative electron boost radiation followed by moderate doses of external beam radiotherapy in limb-sparing treatment of patients with extremity soft-tissue sarcoma

PURPOSE: To analyze long-term prognosis and morbidity after limb-sparing treatment of patients with extremity soft-tissue sarcoma, with intraoperative electron boost radiotherapy (IOERT) followed by a moderate dose of external beam radiotherapy (EBRT). METHODS AND MATERIALS: A total of 153 patients who were treated in a single center from 1991 to 2004 were evaluated. Median IOERT dose was 15 Gy, mean EBRT dose 43 Gy (range, 40-50.4 Gy) in conventional fractionation (1.8-2 Gy). Median duration of follow-up was 33 months. Acute toxicity was assessed with Common Toxicity Criteria; late toxic effects were scored according to European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group criteria. RESULTS: Five-year overall survival and 5-year local control rates were 77% and 78%, respectively. Whereas tumor size, patient age, and EBRT dose did not significantly affect outcome, resection status and grading were significant for survival; resection status and IOERT dose were significant for local control. Extremity salvage until death or time of follow-up was achieved in 90% of our patients, 86% of whom showed excellent limb function without impairment in activities of daily life. Acute toxicity Grade 2-4 was observed in 23% and late toxicity Grade 2-4 in 17% of patients. CONCLUSIONS: Treatment with IOERT combined with moderate doses of external beam irradiation yields high local control and extremity preservation rates in resected extremity soft-tissue sarcoma.     

Feasibility and first results of multimodality treatment, combining EBRT, extensive surgery, and IOERT in locally advanced primary rectal cancer

PURPOSE: To assess the outcome of aggressive multimodality treatment with preoperative external beam radiation therapy (EBRT), extended circumferential margin excision (ECME) and intraoperative electron beam radiation therapy (IOERT) in patients with locally advanced primary rectal cancer. METHODS AND MATERIALS: Thirty-eight patients with primary locally advanced rectal cancer, but without distant metastases, received multimodality treatment. CT-scan showed extension to other structures in 15 patients (39%) and definite infiltration into the surrounding structures in 23 patients (61%). All patients received preoperative EBRT (dose range 25-61 Gy) and 82% received 50.4 Gy. The resection types were: 12 low anterior resections (31%), 14 abdomino-perineal resections (37%), 6 abdomino-transsacral resections (16%), and 6 pelvic exenterations (16%). The IOERT dose ranged from 10 to 17.5 Gy depending on the completeness of the resection. RESULTS: There was no perioperative mortality. The resection margins were microscopically negative in 31 patients (82%), microscopically positive in 4 (10%), and positive with gross residual disease in 3 patients (8%). Pelvic recurrences were observed in 5 patients (13%) including 3 IOERT infield failures. The overall 3-year local control, disease-free survival (DFS), and survival rates were 82%, 65%, and 72%, respectively. Negative resection margins were the most significant prognostic factor with regard to DFS (p = 0.0003) and distant control (p = 0.002) compared with cancer involved surgical margins. CONCLUSION: A high percentage of curative resections can be achieved in this group of patients with locally advanced rectal cancers. Adding IOERT to preoperative EBRT and ECME achieves high local control rates and possibly improves survival.     

Results of radiation therapy for unresected soft-tissue sarcomas

PURPOSE: Definitive radiotherapy is uncommonly used in the management of soft-tissue sarcoma (STS). The purpose of the study was to evaluate the results of radiotherapy for unresected STSs treated in a single institution. METHODS AND MATERIALS: Between 1970 and 2001, 112 patients with STSs underwent radiotherapy for gross disease. Locations of the tumor were 43% in the extremities, 26% retroperitoneal, 24% in the head and neck, and 7% in the truncal wall. Histologic grades were 11% G1 and 89% G2 to G3. Median size of tumor at radiotherapy was 8 cm (range, 1-30 cm). Median radiation dose was 64 Gy (range, 25-87.5 Gy). Twenty percent of patients received chemotherapy. Local control (LC), disease-free survival (DFS), and overall survival (OS) rates were evaluated in univariate (log-rank) and then multivariate (Cox model) analysis to determine prognostic factors for STS. RESULTS: Median follow-up for patients is 139 months (range, 30-365 months). The 5-year actuarial LC, DFS, and OS were 45%, 24%, and 35%, respectively. Tumor size at radiotherapy and radiation dose influenced LC, DFS, and OS in univariate analysis. LC at 5 years was 51%, 45%, and 9% for tumors less than 5 cm, 5 to 10 cm, and greater than 10 cm, respectively. Patients who received doses of less than 63 Gy had 5-year LC, DFS, and OS rates of 22%, 10%, and 14%, respectively, compared with 5-year LC, DFS, and OS rates of 60%, 36%, and 52%, respectively, for patients who received doses of 63 Gy or more. AJCC stage was related to the OS and DFS without statistically significant influence on LC. Use of chemotherapy, histologic grade, age, and location did not influence results. In multivariate analysis, LC was related to total dose (p = 0.02), T size at radiotherapy (p = 0.003), and AJCC stage (p = 0.04); DFS was related to total dose (p = 0.007), T size at radiotherapy (p = 0.01), and AJCC stage (p < 0.0001); and OS was related to AJCC stage (p = 0.0001) and total dose (p = 0.002), but not to T size, at radiotherapy. Major radiotherapy complications were noted in 14% of patients; 27% of patients who received doses of 68 Gy or more had these complications compared with 8% of patients treated with doses of less than 68 Gy. CONCLUSIONS: Definitive radiotherapy for STS should be considered in clinical situations where no acceptable surgical option is available. Higher radiation doses yield superior tumor control and survival. A rise in complications occurs in patients who receive doses of 68 Gy or more, which provides a therapeutic window for benefit in these patients.     

Use of intraoperative electron beam radiotherapy in the management of retroperitoneal soft tissue sarcomas

PURPOSE: To evaluate the disease control, survival results, and tolerance of intraoperative electron beam radiotherapy (IOERT) as a component of treatment for retroperitoneal soft tissue sarcomas. METHODS AND MATERIALS: Between March 1981 and September 1995, 87 patients with primary (n = 43) or recurrent (n = 44) retroperitoneal or intrapelvic sarcomas received IOERT as a component of treatment at the Mayo Clinic. The tumors were high grade in 54 patients (62%) and low grade in 33 (38%). The median tumor size was 10 cm (range 2-36). All patients underwent maximal surgical resection with IOERT; in 72 patients, only microscopic or no residual tumor remained. The IOERT doses ranged from 8.75 to 30 Gy (median 15). All primary tumors received external beam irradiation (EBRT) with a median dose of 48.6 Gy. Thirty-four of the 44 recurrent tumors received EBRT to a median dose of 45 Gy. All patients were followed prospectively for outcome and toxicity evaluation. RESULTS: The median follow-up, based on 46 patients (53%) currently alive, was 3.5 years. The overall estimated 5-year survival was 47%. For patients with tumors > or = 10 cm, the 5-year overall survival was significantly poorer (28%) than for those with smaller lesions (60%) (p = 0.01). Neither primary vs. recurrent status nor tumor grade had a significant impact on survival. Patients with gross residual tumor had a marginally significantly poorer survival compared with patients with microscopic or no residual tumor, with a 5-year survival rate of 37% and 52%, respectively (p = 0.08). A total of 49 patients (56%) experienced failure, including 20 local recurrences (23%). The median time to failure was 2.3 years. Four recurrences were within the IOERT field, 3 within the IOERT and EBRT field, and 13 within the EBRT field alone. The 3- and 5-year estimated local control rate was 77% and 59%, respectively. Local control was marginally significantly affected by the amount of residual tumor, with a 5-year local control rate of 41% for those with gross residual tumor, 60% for those with microscopic residual tumor, and 100% for those with no residual tumor (p = 0.09). Gastrointestinal complications were recorded in 12 incidences (Grade 3 or higher toxicity). These complications were believed to be secondary to surgery and/or EBRT in 10 of the 12 cases. Seven patients had fistula formation, and 3 experienced severe proctitis. Grade 3 peripheral neurologic toxicities occurred in 9 patients (10%), but none had pain as a component of their neuropathy. CONCLUSION: Retroperitoneal soft tissue sarcomas can be treated with an aggressive combined approach of EBRT, surgery, and IOERT, with acceptable toxicity. Local control in primary disease appears to be improved in this retrospective series with this approach. Distant disease control and options for recurrent disease needs further definition.     

Intraoperative electron beam radiotherapy for previously irradiated advanced head and neck malignancies

Purpose: This is a retrospective review to evaluate the role of surgery and intraoperative electron beam radiotherapy (IOERT) in the treatment of patients with previously irradiated advanced head and neck cancers.

Methods and Materials: Between January 1992 and March 1997, 38 patients (31 males, 7 females; median age of 62 years) with recurrent head and neck cancer were treated with maximal resection and IOERT at the Ohio State University (OSU). All had been previously treated with full-course radiotherapy (median 65.1 Gy, range 50–74.4 Gy). Twenty-nine patients (76%) had previously undergone one or more surgical procedures. After maximal surgery the tumor bed was treated with IOERT (single field in 36 patients and 2 fields in 2 patients), most commonly with 6 MeV electrons (87%). The dose administered (at 90% isodose line) was 15 Gy for close or microscopically positive margins in 34 patients and 20 Gy for gross disease in 1 patient. Further external beam radiation therapy (EBRT) was not given.

Results: After a median follow-up of 30 months (range 8–39 months), 24 of the 38 patients (66%) recurred within the IOERT field. Median time to IOERT failure was 6 months (95% CI: 4.3–7.7). The 6-month, 1-, and 2-year control rates within the IOERT volume were 41%, 19%, and 13 %, respectively. Thirty of the 38 patients (79%) recurred in locoregional areas. Median time to locoregional failure was 4 months (95% CI: 3.3–4.7). The 6-month, 1-, and 2-year locoregional control rates were 33%, 11%, and 4%, respectively. Distant metastases ocurred in 7 patients, 5 in association with IOERT failure and 2 with locoregional failure. Median overall survival was 7 months (95% CI: 4.7–9.3). The 6-month, 1-, 2-, and 3-year actuarial survival rates were 51%, 21%, 21%, and 8%, respectively. Major treatment-related complications occurred in 6 patients (16%).

Conclusion: IOERT alone, at the dose used, is not sufficient for control of recurrent, previously irradiated head and neck cancers. Since higher IOERT doses are associated with high morbidity, we are currently evaluating the addition of limited EBRT dose and/or brachytherapy to improve the local control of these poor prognostic recurrent tumors, with acceptable morbidity.     

Long-term outcomes for synovial sarcoma treated with conservation surgery and radiotherapy

PURPOSE: To evaluate prognostic factors and treatment outcomes in patients with localized synovial sarcoma treated with conservation surgery and radiotherapy (RT). METHODS AND MATERIALS: Between 1960 and 2003, 150 patients with nonmetastatic synovial sarcoma were treated with conservation surgery and RT. The majority of patients (81%) were aged >20 years. Sixty-eight percent received postoperative RT, and 32% received preoperative RT. Forty-eight percent received adjuvant chemotherapy. RESULTS: Median follow-up was 13.2 years. Overall survival (OS) rates at 5, 10, and 15 years were 76%, 57%, and 51%, respectively. Corresponding disease-free survival (DFS) rates were 59%, 52%, and 52%, respectively. Tumor size >5 cm predicted worse OS, DFS, disease-specific survival (DSS), and higher rate of distant metastases (DM). Age >20 years predicted worse DFS and DSS but not OS. Local control (LC) was 82% at 10 years. Positive or unknown resection margins predicted inferior LC rates. Forty-four percent developed DM by 10 years. Only 1% developed nodal metastases. Analysis of outcomes by treatment decade showed no significant differences with respect to LC and DM rates. CONCLUSIONS: Synovial sarcoma is adequately controlled at the primary site by conservation surgery and RT. Elective nodal irradiation is not indicated. Rates of development of DM and subsequent death from disease remain high, with no significant improvement in outcomes for this disease in the past four decades.     

Intraoperative electron beam radiation therapy for locally recurrent rectal carcinoma.

PURPOSE: Treatment results for locally recurrent rectal cancers are poor. This is a result of the fact that surgery is hampered due to the severance of the anatomical planes during the primary procedure and that radiotherapy is limited by normal tissue tolerance, especially after previous irradiation. This paper describes the results of a combined treatment modality in this patient group. METHODS AND MATERIALS: From 1994 to 1998, 37 patients with locally recurrent rectal cancer, but without distant metastatic disease, received a combined treatment consisting of 50.4 Gy preoperative irradiation or, in case of previous radiotherapy, 30 Gy reirradiation or no irradiation, followed by radical surgery and intraoperative electron beam radiotherapy boost. RESULTS: Fifteen patients received a radical resection (R0), eight a microscopic irradical resection (R1), and 14 a macroscopic irradical resection (R2). The overall 3-year local control (LC), disease-free survival (DFS), and overall survival rates were 60%, 32%, and 58% respectively. Radicality of resection (R0/R1 vs. R2) turned out to be the significant factor for improved survival (p < 0.05), DFS (p = 0.0008), and LC (p = 0.01). Preoperative (re-)irradiation is the other significant factor in survival (p = 0.005) and DFS (p = 0.001) and was almost significant for LC (p = 0.08). After external beam radiation therapy (EBRT) a significantly higher resection rate was obtained (R0/R1 vs. R2 p = 0.001). Symptomatic peripheral local recurrences have a significantly worse prognosis and higher rate of R2-resection (p = 0.0005). CONCLUSION: Centralization of locally recurrent rectal cancer patients enabled the development of an aggressive multimodality treatment, which in turn led to promising results. Distant failure is still a drawback.     

Long-term results of intraoperative presacral electron boost radiotherapy (IOERT) in combination with total mesorectal excision (TME) and chemoradiation in patients with locally advanced rectal cancer

BACKGROUND: We analyzed the long-term results of patients with locally advanced rectal cancer using a multimodal approach consisting of total mesorectal excision (TME), intraoperative electron-beam radiation therapy (IOERT), and pre- or postoperative chemoradiation (CRT). PATIENTS AND METHODS: Between 1991 and 2003, 210 patients with locally advanced rectal cancer (65 International Union Against Cancer [UICC] Stage II, 116 UICC Stage III, and 29 UICC Stage IV cancers) were treated with TME, IOERT, and preoperative or postoperative CHT. A total of 122 patients were treated postoperatively; 88 patients preoperatively. Preoperative or postoperative fluoropyrimidine-based CRT was applied in 93% of these patients. RESULTS: Median age was 61 years (range, 26-81). Median follow-up was 61 months. The 5-year actuarial overall survival (OS), disease-free survival (DFS), local control rate (LC), and distant relapse free survival (DRS) of all patients was 69%, 66%, 93%, and 67%, respectively. Multivariate analysis revealed that UICC stage and resection status were the most important independent prognostic factors for OS, DFS, and DRS. The resection status was the only significant factor for local control. T-stage, tumor localization, type of resection, and type of chemotherapy had no significant impact on OS, DFS, DRS, and LC. Acute and late complications > or =Grade 3 were seen in 17% and 13% of patients, respectively. CONCLUSION: Multimodality treatment with TME and IOERT boost in combination with moderate dose pre- or postoperative CRT is feasible and results in excellent long-term local control rates in patients with intermediate to high-risk locally advanced rectal cancer.     

Intraoperative radiation therapy for locally advanced recurrent rectal or rectosigmoid cancer

Recurrent rectal or rectosigmoid cancer is a difficult therapeutic problem. A treatment program of external beam irradiation, surgery, and intraoperative irradiation has been used for 41 patients. The 5-year actuarial local control and disease-free survival of all 41 patients was 30% and 16%, respectively. Subset analysis demonstrated differences in outcome by extent of surgical resection. The 5-year actuarial local control and disease-free survival of 27 patients undergoing complete resection was 47% and 21%, respectively. By contrast, the outcome of 14 patients undergoing partial resection was poor, with a 5-year actuarial local control and survival of 21% and 7%, respectively. Late complications included soft tissue or peripheral nerve injury, with many of these resolving within 4–18 months. Local control and disease-free survival rates are favorable in comparison with the results achieved by aggressive surgery. Patients who achieve a gross total resection at intraoperative irradiation have a markedly better prognosis than that of patients with residual gross disease. © 1995 Wiley-Liss, Inc.     

Duodenal adenocarcinoma: patterns of failure after resection and the role of chemoradiotherapy

PURPOSE: To report patterns of disease recurrence after resection of adenocarcinoma of the duodenum and compare outcomes between patients undergoing surgery only vs. surgery with concurrent chemotherapy and radiation therapy (CT-RT). METHODS AND MATERIALS: This was a retrospective analysis of all patients undergoing potentially curative therapy for adenocarcinoma of the duodenum at Duke University Medical Center and affiliated hospitals between 1975 and 2005. Overall survival (OS), disease-free survival (DFS), and local control (LC) were estimated using the Kaplan-Meier method. Univariate regression analysis evaluated the effect of CT-RT on clinical endpoints. RESULTS: Thirty-two patients were identified (23 M, 9 F). Median age was 60 years (range, 32-77 years). Surgery alone was performed in 16 patients. An additional 16 patients received either preoperative (n = 11) or postoperative (n = 5) CT-RT. Median RT dose was 50.4 Gy (range, 12.6-54 Gy). All patients treated with RT also received concurrent 5-fluorouracil-based CT. Two patients treated preoperatively had a pathologic complete response (18%), and none had involved lymph nodes at resection. Five-year OS, DFS, and LC for the entire group were 48%, 47%, and 55%, respectively. Five-year survival did not differ between patients receiving CT-RT vs. surgery alone (57% vs. 44%, p = 0.42). However, in patients undergoing R0 resection, CT-RT appeared to improve OS (5-year 83% vs. 53%, p = 0.07). CONCLUSIONS: Local failure after surgery alone is high. Given the patterns of relapse with surgery alone and favorable outcomes in patients undergoing complete resection with CT-RT, the use of CT-RT in selected patients should be considered.     

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 ≥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 ≥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.     

Endometrial cancer with para-aortic adenopathy: patterns of failure and opportunities for cure.

PURPOSE: To examine the outcome of patients with advanced endometrial cancer whose para-aortic involvement was diagnosed pathologically or lymphographically. METHODS AND MATERIALS: Fifty patients from four institutions were treated between 1959 and 1990 with preoperative, post-operative, and primary radiotherapy. Para-aortic disease was diagnosed pathologically in 26 patients and lymphographically in the remaining 24 patients. Pathologically diagnosed patients underwent debulking of grossly involved nodes. All patients received external beam treatment through pelvic and para-aortic portals. Median prescribed dose to the pelvic and para-aortic fields was 50 and 47 Gy, respectively. Those treated with primary or pre-operative irradiation also received intrauterine brachytherapy. RESULTS: The actuarial 5-year disease-free survival was 46% for all patients. Para-aortic failure was significantly decreased among patients undergoing lymph node resection (13% versus 39%, respectively). Relapse-free survival and pelvic control tended to improve among patients receiving surgery plus irradiation in comparison to those treated by irradiation alone. Distant metastases were most common among patients with high grade lesions. CONCLUSIONS: Long-term disease-free survival is achievable in endometrial cancer patients with para-aortic lymphadenopathy who are treated with extended-field radiotherapy. Cure is mot attainable among patients with well differentiated, early clinical stage disease who receive combined modality treatment. Survival and local failure are similar for radiologically and pathologically diagnosed patients; however, para-aortic failure as a component of local failure was increased in patients who did not undergo surgical debulking of the adenopathy.     

Intraoperative electron beam radiation therapy for retroperitoneal soft tissue sarcoma

From December 1981 to December 1989, 20 patients with primary or recurrent retroperitoneal sarcoma received 4000 to 5000 cGy of external beam radiation therapy (EBRT) in conjunction with surgical resection and intraoperative radiation therapy (IORT). Seventeen of 20 patients underwent complete (14 patients) or partial (3 patients) resection. Three patients had shown evidence of metastases after EBRT by the time of surgery. The 4-year actuarial local control and disease-free survival rates of the 17 patients undergoing resection were 81% and 64%, respectively. Twelve patients received IORT at the time of resection for microscopic disease (10 patients) or gross residual sarcoma (2 patients). Of the ten patients receiving IORT for microscopic tumor, one patient has died of local failure and peritoneal sarcomatosis and two patients have died of distant metastases only. The remaining seven patients are disease-free. One patient treated for gross residual sarcoma has experienced a local failure 1 year after IORT and is without disease 7 years after salvage chemotherapy. The other patient treated for gross residual sarcoma has died of local failure. Five patients did not receive IORT at the time of resection because of the extensive size of the tumor bed. Three of these patients are disease-free with one patient alive with lung metastases and one patient dying of hepatic metastases. Aggressive radiation and surgical procedures appear to provide satisfactory resectability and local control with acceptable tolerance.     

High-dose-rate intraoperative radiation therapy (HDR-IORT) for retroperitoneal sarcomas

PURPOSE: Retroperitoneal sarcomas represent a formidable challenge to the treating oncologist due to their location, large size, and poor prognosis. The purpose of this study was to determine if the addition of high-dose-rate intraoperative radiation therapy (HDR-IORT) to surgery and external beam radiotherapy (EBRT) would improve the outcome in these patients. METHODS AND MATERIALS: Thirty-two patients with retroperitoneal soft tissue sarcoma were prospectively treated according to a protocol that included maximal tumor resection, HDR-IORT, and postoperative EBRT when feasible. Twelve patients presented with primary and 20 with locally recurrent disease. The tumors were high-grade in 20 patients and low-grade in 12 patients. Complete gross resection was achieved in 30 patients. HDR-IORT was given to a dose of 12-15 Gy. Additional EBRT was given to 78% of patients to a dose of 45-50.4 Gy. The two patients with gross residual disease received an additional I-125 permanent implant to a median peripheral dose of 140-160 Gy. The median follow-up was 33 months (range 1-77 mo). RESULTS: The 5-year actuarial local control rate for the whole group was 62%. For patients with primary disease, the local control rate was 74% compared to 54% in patients with recurrent disease (p = 0.4). The overall 5-year distant metastasis-free survival rate was 82%. In patients with high-grade tumors the rate was 70% vs. 100% in those with low-grade tumors. This difference was statistically significant, p = 0.05. The 5-year disease-free and overall survival rates were 55% and 45%, respectively. The most common type of post-treatment complication was gastrointestinal obstruction (18%) followed by fistula formation (9%), peripheral neuropathy (6%), hydronephrosis (3%), and wound complication (3%). CONCLUSIONS: We are encouraged by the favorable local control rate and the acceptable morbidity with this new technique applied to a challenging patient population.     

Intracranial ependymomas treated with radiotherapy: long-term results from a single institution

The purpose of the study is to report long-term outcomes following surgery and radiotherapy for intracranial ependymoma. We retrospectively reviewed the medical records of patients treated with radiotherapy for localized intracranial ependymomas from 1964 to 2006. Patients with subependymomas and ependymoblastomas, and those undergoing re-irradiation, were excluded. Our study population is 44 patients: 37 infratentorial lesions, 7 supratentorial. All patients had postoperative radiotherapy; most received sub-total resection and one-third received gross total resection. Most patients received local radiotherapy alone (median tumor dose 55 Gy); one-quarter received craniospinal irradiation (median dose 35 Gy). The 5- and 10-year local-control rates for all patients were 60 and 46%, respectively; 23% of local recurrences occurred after 5 years. Ninety-five percent of the patients recurred at the primary site; 5% had spinal seeding with no evidence of disease at the primary site. No patient who received craniospinal irradiation recurred in the spine. The 5- and 10-year disease-free survival and overall-survival rates for all patients were 60 and 42% and 57 and 43%, respectively. On multivariate analysis, age ≥18 years, gross total resection and infratentorial site were associated with improved local control. No patient with continuous local control had grade 4 or 5 toxicities; 27% of patients had grade 2 or 3 toxicities. One patient developed a radiation-induced meningioma >20 years after radiotherapy. Maximal safe resection followed by adjuvant radiotherapy provided local control in one-half of patients at 10 years. Age, extent of surgery, and location were identified as major independent prognostic factors in patients with intracranial ependymomas.     

Intraoperative electron beam radiation therapy for recurrent locally advanced rectal or rectosigmoid carcinoma

A multimodality approach of moderate-dose to high-dose preoperative radiation therapy, surgical resection, and intraoperative electron beam radiation therapy (IORT) has been used for patients with locally recurrent rectal or rectosigmoid carcinoma. The 5-year actuarial local control and disease-free survival for 30 patients undergoing this treatment program were 26% and 19%, respectively. The most important factor predicting a favorable outcome was complete resection with negative pathologic resection margins. The determinant local control and disease-free survival for 13 patients undergoing complete resection were 62% and 54%, respectively, whereas for 17 patients undergoing partial resection these figures were 18% and 6%, respectively. There did not appear to be a difference in local control or survival based on the original surgical resection (abdominoperineal resection versus low anterior resection). However, the likelihood of obtaining a complete resection after preoperative radiation therapy was higher in patients who had previously undergone a low anterior resection than patients undergoing prior abdominoperineal resection. For the 30 patients undergoing external beam irradiation, resection, and IORT, the most significant toxicities were soft tissue or sacral injury and pelvic neuropathy. Efforts to further improve local control are directed toward the concurrent use of chemotherapy (5-fluorouracil with and without leucovorin) as radiation dose modifiers during external beam irradiation and the use of additional postoperative radiation therapy.     

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.     

Surgical resection and radiotherapy for primary retroperitoneal soft tissue sarcoma.

METHODS AND MATERIALS: Forty-five patients were consecutively treated for primary retroperitoneal soft tissue sarcoma with surgery in combination with radiation therapy in the same institution. The median follow-up time was 53 months (7-108). RESULTS: Seventeen (38%) patients had clear microscopic margins (R0 resection), 26 patients (58%) had gross complete surgical excision (R1 resection) and two patients (4%) had a macroscopic residual disease (R2 resection). External radiotherapy doses ranged from 40.8 to 59.4 Gy (mean and median: 49 Gy). Seventeen patients underwent intraoperative radiation therapy (IORT). Moreover, 11 patients received chemotherapy. The overall 1-, 2-, and 5-year survival for all 45 patients were 93, 85 and 60%, respectively. The 1-, 2-, and 5-year locoregional relapse-free rate for the whole group was 91, 70 and 40%, respectively. In univariate analysis, quality of surgery was the only variable to show a significant effect for overall survival (P=0.0386) and for local control (P=0.0059). Tumor size and tumor grade had no statistically significant effect. For the patients receiving IORT+external beam radiation therapy, no difference was observed for survival or locoregional control. The most frequent acute side effects treatment complications were radiation-induced nausea or vomiting (42%) and moderate enteritis (30%). Significant late morbidity was observed for two patients. CONCLUSIONS: This study confirms the feasibility of external postoperative radiotherapy with an acceptable level of toxicity. However, the high rate of local relapses (especially in field of radiation) does not demonstrate the usefulness of radiotherapy at the level of dose used and further preferably randomized studies should be planned.     

Radiation therapy for control of soft-tissue sarcomas resected with positive margins

PURPOSE: Positive margins (PM) remain after surgery in some soft-tissue sarcoma (STS) patients. We investigated the efficacy of radiation therapy (RT) in STS patients with PM. METHODS AND MATERIALS: A retrospective chart review was performed on 154 patients with STS at various anatomic sites with PM, defined as tumor on ink, who underwent RT with curative intent between 1970 and 2001. Local control (LC), disease-free survival (DFS), and overall survival (OS) rates were evaluated by univariate (log-rank) and multivariate analysis of prognostic and treatment factors. RESULTS: At 5 years, actuarial LC, DFS, and OS rates were: 76%, 46.7%, and 65.2%, respectively. LC was highest with extremity lesions (p < 0.01), radiation dose >64 Gy (p < 0.05), microscopically (vs. grossly visible) positive margin (p = 0.03), and superficial lesions (p = 0.05). Patients receiving >64 Gy had higher 5-year LC, DFS, and OS rates of 85%, 52.1%, and 67.8% vs. 66.1%, 41.8%, and 62.9% if < or =64 Gy, p < 0.04. OS was worse in patients with G2/G3 tumors with local failure (LF), p < 0.001. Other known prognostic factors, including grade, stage, size, and age (>50), also significantly influenced OS. By multivariate analysis, the best predictors of LC were site (extremity vs. other), p < 0.01 and dose (>64 vs. < or =64 Gy), p < 0.05; the best predictors for OS were size, p < 0.001, gross vs. microscopic PM, p < 0.05, and LF, p < 0.01. CONCLUSION: Local control is achieved in most PM STS patients undergoing RT. Doses >64 Gy, superficial location, and extremity site are associated with improved LC. OS is worse in patients with tumors with lesions >5 cm, grossly positive margins, and after local failure.