Nerve tolerance to high-dose-rate brachytherapy in patients with soft tissue sarcoma: a retrospective study

Background  

Brachytherapy, interstitial tumor bed irradiation, following conservative surgery has been shown to provide excellent local control and limb preservation in patients with soft tissue sarcomas (STS), whereas little is known about the tolerance of peripheral nerves to brachytherapy. In particular, nerve tolerance to high-dose-rate (HDR) brachytherapy has never been properly evaluated. In this study, we examined the efficacy and radiation neurotoxicity of HDR brachytherapy in patients with STS in contact with neurovascular structures.     

软组织肉瘤保存肢体的新技术应用

应用广泛切除术及高剂量率后装内照射新技术（Ｂｒａｃｈｙｔｈｅｒａｐｙ），治疗累及重要血管及神经的软组织肉瘤，达到控制预防局部复发，保存肢体功能的目的。５例肢体软组织肉瘤经治疗后均生存，随访未见局部复发及远处转移。作者介绍了保存肢体手术及肿瘤床１９２铱置管内照射的技术，同时建议对以往截肢指征应慎重考虑，只有在各种综合治疗失败情况下才考虑截肢。     

Limb salvage therapy for soft tissue sarcomas of the foot

From 1974 to 1988, 20 patients with soft tissue sarcomas of the foot underwent attempted limb preservation at UCLA. Eighteen patients had localized tumor and two had metastases. Sixteen patients had previously untreated tumors and four patients had experienced 2-4 local recurrences before definitive management. Eleven patients had grade 3 sarcomas and nine had grade 2 sarcomas. Fourteen patients had an excisional biopsy and six had an incisional biopsy. At the time of definitive local treatment, nine patients had palpable tumor ranging from 2-10 cm (median 5 cm). Sixteen patients received sequential preoperative chemotherapy and irradiation followed by attempted conservative resection. Four patients underwent immediate conservative resection followed by postoperative irradiation. Preoperative chemotherapy was administered over 3 days intraarterially, intravenously or by a combination of routes. Fifteen patients received 60-90 mg doxorubicin and one received 120 mg doxorubicin plus 220 mg cisplatinum. Preoperative irradiation was delivered in 350 cGy fractions to total doses of 3500 cGy (one patient), 2800 cGy (8) or 1750 cGy (7). Postoperative irradiation doses were 4140-6480 delivered in 180-200 cGy fractions. Fifteen of 16 preoperatively treated patients had limb salvage surgery. Four of these 15 had positive histopathologic margins and none received postoperative irradiation. One patient required a primary amputation due to gross involvement of the os calcis. Three of four patients undergoing immediate conservative excision had positive margins and one had gross residual disease. Five patients received chemotherapy following local treatment: 3 adjuvantly and 2 for metastatic disease. Follow-up for salvage patients ranged from 6 to 99 months (median 36). Local control was achieved in 17 of 19 (90%). Two patients recurred in-field at 24 and 30 months. Fourteen of 15 preoperatively treated and salvaged patients maintained local control. Three of four managed with excision and postoperative irradiation were controlled. The actuarial local control at 3 years was 83%. One patient recurred in the inguinal lymph nodes and three patients died of metastatic disease. The actuarial survival and relapse-free survival at 3 years were 83% and 63%. Eleven patients developed acute complications and four had late complications. Of 14 patients surviving with local control, function was good or excellent in 86%. No patient has required an amputation for complications or a dysfunctional foot. Limb salvage therapy for a selected patient with a soft tissue sarcoma of the foot can reasonably be expected to result in a high probability of local control and useful function without compromising survival.     

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.     

Combined surgical resection and iridium 192 implantation for locally advanced and recurrent desmoid tumors

Thirty-eight histologically confirmed desmoid tumors were treated with conservative surgical resection and interstitial iridium 192. Patients included in this series constituted a poor prognostic group. Seventy five percent (75%) had previous recurrences of their disease and 50% had tumors 8 cm or greater in size. In addition, 16% of the patients had gross residual disease after surgical excision and 79% had positive or close margins of resection. With a median follow-up of 5.5 years, the 5-year actuarial in-field local control rate was 75% and the overall local control rate was 66%. Four of the 12 local recurrences developed at the periphery of the implant volume and four patients failed at least 3 cm or more beyond the treated volume. After salvage therapy, the 5-year actuarial local control rate was 95%. Two patients required amputation for recurrent disease. Thirty of 34 patients remain free of disease with an excellent functional result achieved. The authors conclude that surgical resection and postoperative interstitial iridium 192 is effective therapy for patients with desmoid tumors. Despite the fact that most patients in this series had bulky, recurrent tumors, excellent long-term local control and limb function were achieved.     

Intraoperative electron beam radiation therapy for primary locally advanced rectal and rectosigmoid carcinoma

To improve local control and survival in patients with primary locally advanced rectal and rectosigmoid carcinoma, intraoperative electron beam radiation therapy (IORT) has been used with a combination of moderate- to high-dose preoperative radiation therapy and surgical resection. Sixty-five patients underwent resection with the intention of using IORT if areas at high risk for local recurrence were apparent at surgery. For 20 patients undergoing complete resection with IORT, the 5-year actuarial local control and disease-free survival (DFS) was 88% and 53%, respectively. The results for 22 patients with pathologically documented residual carcinoma were less satisfactory with a 5-year actuarial local control and DFS of 60% and 32%, respectively. In this latter group, local control and DFS correlated with the extent of residual disease: patients with only microscopic disease had a 5-year actuarial local control and DFS of 69% and 47%, respectively, whereas for patients with macroscopic disease, these figures were 50% and 17%, respectively. For 18 patients undergoing complete resection without IORT or additional postoperative radiation therapy, the 5-year actuarial local control and DFS was 67% and 53%, respectively. Because local failure will occur in at least 30% of patients undergoing partial resection with or without IORT as well as patients undergoing complete resection of advanced tumors without IORT, additional postoperative radiation therapy should be considered.     

Soft tissue sarcoma. Integration of brachytherapy, resection, and external irradiation

Between December 1981 and August 1988, 63 patients with clinically localized nonretroperitoneal soft tissue sarcomas underwent 65 brachytherapy procedures in conjunction with conservative resection with (61 tumors) or without (four tumors) external beam irradiation. Implant doses of 1500 to 2000 cGy were combined with 4500 to 5000 cGy of external irradiation. External irradiation was given preoperatively for larger lesions near bone or neurovascular structures, whereas it was used postoperatively for smaller, more resectable lesions or those that had previously been inadequately excised. There were 47 high-grade tumors, 34 tumors greater than 5 cm, and nine patients with recurrent lesions (five with previous irradiation). With mean follow-up of 20 months, conclusions on local control are tentative, but only two of 56 tumors (4%) with brachytherapy as part of initial management had recurred locally and three of nine recurrent tumors had re-recurred locally. Only one of five local recurrences was within the implanted volume. Only two of 40 implantations (5%) performed at initial resection followed by postoperative external irradiation led to wound complications, whereas four of 16 implantations (25%) performed at resection after preoperative external irradiation were associated with wound problems. This technique does not increase local morbidity and may enhance local tumor control in comparison with either external radiation or brachytherapy alone as an adjuvant to conservative resection.     

Phase I/II trial of pre-operative radiation therapy and coloanal anastomosis in distal invasive resectable rectal cancer.

A total of 22 patients with the diagnosis of invasive, resectable, primary adenocarcinoma of the rectum limited to the pelvis were enrolled on a Phase I/II trial of pre-operative radiation therapy+low anterior resection/coloanal anastomosis. By pre-operative assessment, all patients had invasive tumors involving the distal half of the rectum and required an abdominoperineal resection. The median tumor size was 4 cm (1.5-6 cm) and the median distance from the anal verge was 4 cm (3-7 cm). The whole pelvis received 4680 cGy followed by a 360 cGy boost to the primary tumor bed. The median follow-up was 29 months (10-60 months). Of the 21 patients who underwent resection, 10% had a complete pathologic response and 90% were able to successfully undergo a low anterior resection/coloanal anastomosis. The incidence of local failure as a component of failure was crude: 23% and 4-year actuarial: 32%. The 4-year actuarial survival was 61%. No patients experienced Grade 3 or 4 toxicity while receiving radiation therapy, and 6% developed a partial disruption of the anastomosis. Of the patients who underwent a low anterior resection/coloanal anastomosis, 89% had a good or excellent functional result. This technique may be an alternative to an abdominoperineal resection in selected patients. Further follow-up is needed in order to determine if this approach ultimately has similar local control and survival rates as an abdominoperineal resection.     

Treatment of locally advanced rectal cancer with external beam radiation, surgical resection, and intraoperative radiation therapy

To try to improve the local control and survival of patients with locally advanced rectal cancer we have used a combination of high-dose pre-operative radiation therapy to 5,040 cGy followed by surgical resection and intraoperative electron beam radiation therapy (IORT) when there was visible or palpable residual disease, microscopically positive surgical margins, or persisting tumor adherence. A total of 75 patients were taken to surgery for resection +/- IORT who did not have distant metastases. Of the 49 patients with primary tumors, 11 did not have IORT as the tumor was thought to be completely resected. Of these 11, there were two local recurrences and a 3-year survival of 71%. Thirty-six patients with primary tumors had resection (20 complete, 16 partial) plus IORT, with a 3-year survival of 58% and three local failures. Twenty-six additional patients were treated for locally advanced recurrence of whom four could not receive IORT because of pelvic size or the extent of tumor. Of the 22 who received IORT, 7/9 with complete resection, 2/8 with partial resection, and 1/5 with no resection had local control with an overall 3-year actuarial survival of 32%. The local control and survival results in the primary tumors appear favorable compared to other series in the literature and suggest benefit to the use of IORT. For patients treated for local recurrence, local control and long-term survival can be obtained, but the results are not as encouraging as for the primary tumors.     

Treatment and local control of primary extremity soft tissue sarcomas.

BACKGROUND AND OBJECTIVES: Modern series of adult extremity soft tissue sarcomas utilize combinations of modalities in all patients. Remaining questions: 1) is it necessary to strive for wide margins in the multimodality era; 2) to use adjuvant therapy in every high-grade sarcoma? 3) Does previous partial or marginal resection seriously interfere with the definitive resection? METHODS: In a retrospective review of 194 extremity soft tissue sarcomas (1977-1994), limb preservation was possible in 181/194 (93%) of cases. Patients with narrow margins received adjuvant radiation. Some patients were referred after partial (n = 39) or "complete" (n = 63) excision. RESULTS: Local recurrence was observed in 181/141 (13%) of patients treated with wide or compartmental resection, and in 10 of 42 (24%) of those treated with conservative resection plus radiation (P = 0.14). The 5-year survival rate for grade III, >/=5-cm sarcomas was not significantly different (P = 0.82) with adjuvant (46%) or without (48%) adjuvant systemic chemotherapy. Five-year survival varied (P = 0.0001) according to grade. Patients referred with partial, or "complete" (63%, 38/63, had residual tumor at reoperation) excision had a local recurrence rate of 8% and 6%, and 5-year survival rates of 75% and 84%, respectively. CONCLUSIONS: 1) It is important to strive for wide margins even when adjuvant radiation is intended. 2) When a wide margin is possible, adjuvant radiation may not be necessary. 3) Adjuvant systemic chemotherapy may be considered for high-grade tumors, preferably within a prospective protocol. 4) A partial or "complete" excision of the tumor before referral to a tertiary center does not appear to compromise the limb preservation, local control, or survival rates of these patients.     

Organ preservation with interstitial radiation for base of tongue cancer

Management options for squamous cell carcinoma of the base of tongue include surgical resection (often with adjuvant radiation), definitive external radiation and external combined with interstitial radiation. The reported series is a single institution experience with interstitial radiation for base of tongue cancer. Twenty patients were treated definitively with interstitial radiation as a boost to external radiation, and four patients were treated palliatively with interstitial radiation alone for recurrent base of tongue cancers or disease arising in a previously irradiated base of tongue. Patient, tumor, and treatment details were analyzed relative to disease control and posttreatment patient function. The 5-year actuarial local control, locoregional control, distant metastasis-free survival, overall disease-free survival, and actuarial overall survival of the definitively treated patients were 86%, 84%, 57%, 41%, and 30%, respectively. The 5-year actuarial rate of tolerating a normal diet was 86%, and all long-term survivors had normal speech function. Of the four patients treated palliatively with interstitial implant alone for recurrent disease (three patients), or a second primary cancer in a previously irradiated site (one patient), local control was obtained in three and long-term disease-free survival was obtained in one. Interstitial implantation combined with external radiation is associated with a high rate of disease eradication with preservation of speech and swallow function. Interstitial radiation alone can achieve effective palliation.     

Sphincter preservation for cancer of the distal rectum using high dose preoperative radiation

Sphincter preservation surgery for cancer of the distal rectum is recognized as being associated with a high incidence of local recurrence. High dose preoperative radiation with new surgical techniques is described as an attempt to widen the scope of sphincter preservation in patients who by conventional management would have an abdomino-perineal resection and permanent colostomy and to reduce the incidence of local recurrence. Since 1976, 121 patients with cancers of the rectum have selectively been treated with high dose preoperative radiation (4000 cGy to 6000 cGy) followed by combined abdominotranssacral resection (56); transanal abdominotransanal resection (28); anterior resection (21), or a full thickness wide local excision (16). This report details the results of 43 patients observed for a minimum of 2 years whose tumors were located from 0-6 cm of the dentate line. All patients received the full course of preoperative radiation, a minimum dose of 4000-4500 cGy in approximately 4 1/2 weeks that was delivered using 180-250 cGy per fraction. Patients with tumor fixation were given an additional boost of 1000-1500 cGy preoperatively. Surgery was carried out 4-6 weeks following the completion of radiation. There was no perioperative mortality. Anastomotic failure occurred in 3 patients and was reconstituted in two. Sphincter function was maintained in all but 6 patients (86%), 2 of these had a subsequent abdominoperineal resection, and 3 a diverting colostomy. Seven of 43 (16%) patients with tumors below 6 cm developed a local recurrence, and 6 of the 7 recurrences occurred in patients with fixed tumors, especially those located from 0-3 cm from the dentate line. Eleven patients are dead of disease. The 5-year actuarial survival rate for this group is 72%. Results indicate that high dose preoperative radiation can significantly extend the scope of sphincter preservation to selected cancers of the disal rectum with excellent survival without increasing the risk of pelvic perineal recurrence.     

Radiation therapy of retroperitoneal soft tissue sarcomas

Between 1971 and 1982, 23 patients have been treated with radiation therapy at the Massachusetts General Hospital (MGH) for retroperitoneal soft tissue sarcomas. Seventeen patients were treated with curative intent and six with palliative intent. Of the patients treated with curative intent, the 5 year actuarial survival rate was 54% and the 5 year actuarial local control rate was also 54%. With a complete surgical resection local tumor control was obtained in 5 of 7 patients (71%), 4 of 7 (57%) with incomplete resection and 1/3 (33%) with no resection having local control. The radiation dose appeared to influence tumor control with 2 of 6 patients (33%) having local control with less than 5,000 cGy compared to 0 of 5 patients with doses of 5,000 to 6,000 cGy and 5 of 6 (83%) with doses greater than 6,000 cGy. An effect of tumor grade on either local control or on rate of metastasis formation could not be demonstrated in this series. Long-term local control and survival appears to be associated with maximal surgical resection and high dose radiation therapy.     

Rectal carcinoma. Long-term experience with moderately high-dose preoperative radiation and low anterior resection.

This report updated an analysis of a 14-year experience of moderately high-dose (4500 to 5000 cGy) preoperative radiation as an adjuvant to low anterior resection of 95 cases of adenocarcinoma of the rectum. The treatment was well tolerated without treatment-related mortality and with a low incidence (5.2%) of severe complications. The local recurrence rate was 4.2%, and distant failure rate was 10.5%. At 5 years, the actuarial survival rate was 66% and the disease-free survival rate was 64%. At 10 years, the actuarial survival rate and disease-free survival rate were 52%. The authors concluded that moderately high-dose (4500 to 5000 cGy) neoadjuvant radiation in clinically resectable adenocarcinoma of the rectum in which one segment of the anastomosis was in the preoperative radiation field is a safe, effective adjuvant to low anterior resection and that it offered patients excellent local control, long-term survival, and sphincter preservation. Results could be enhanced by chemotherapy, and the authors urged well-designed prospective randomized multicenter trials to determine the most appropriate drugs, dosage, and sequencing of co-adjuvant preoperative radiation therapy and chemotherapy with surgery.     

Low-dose-rate intraoperative brachytherapy combined with external beam irradiation in the conservative treatment of soft tissue sarcoma

PURPOSE: Conservative treatment of soft tissue sarcomas most often implies combination of surgical resection and irradiation. The aim of this study was to evaluate low-dose-rate intraoperative brachytherapy, delivered as a boost, in the local control of primary tumors, with special concern about treatment complications. METHODS AND MATERIALS: Between 1986 and 1995, 112 patients underwent intraoperative implant. This report focuses on the group of 58 patients with primary sarcomas treated by combination of conservative surgery, intraoperative brachytherapy, and external irradiation. Most of the tumors were located in the lower limbs (46/58-79%). Median size of the tumor was 10 cm, most of the lesions being T2-T3 (51/58-88%), Grade 2 or 3 (48/58-83%). The mean brachytherapy dose was 20 Gy and external beam irradiation dose 45 Gy. In 36/58 cases, iridium wires had to be placed on contact with neurovascular structures. RESULTS: With a median follow-up of 54 months, the 5-year actuarial survival was 64.9%, with a 5-year actuarial local control of 89%. Of the 6 patients with local relapse, 3 were salvaged. Acute side effects, essentially wound healing problems, occurred in 20/58 patients, late side effects in 16/58 patients (7 neuropathies G2 to G4). No amputation was required. The only significant factor correlated with early side effects was the location of the tumor in the lower limb (p = 0.003), and with late side effects the vicinity of the tumor with neurovascular structures (p = 0.009). CONCLUSION: Brachytherapy allows early delivery of a boost dose in a reduced volume of tissue, precisely mapped by the intraoperative procedure. Combined with external beam irradiation, it is a safe and efficient treatment technique leading to high local control rates and limited functional impairment.     

Whole abdominal irradiation following chemotherapy in advanced ovarian carcinoma

One hundred and sixteen patients with advanced ovarian carcinoma, who underwent primary cytoreductive surgery, received 6–11 courses of chemotherapy by cis-platin (50 mg/m²) and adriamycin (50 mg/m²)every 21 days. This was followed by second lood laparotomy in 66 patients with no clinical evidence of disease. Consolidation abdominal irradiation was administered to 43 patients. Two techniques of irradiation were employed: between 1980–1983 whole abdominal irradiation was used and patients were to receive 3000 cGy in 4 weeks (Schedule I). Due to myelosuppression only 13 of 26 patients (50%) completed the planned dose of radiation. between 1983–1985 the target volume was divided into upper and lower parts. First, the lower abdomen received 3000 cGy in 3 weeks, and then the upper abdomen received the same dose (Schedule II). Sixteen of seventeen patients (94%) thus treated, completed the planned dose of radiation. The actuarial survival for all 116 patients was 28% of 5 years. Irradiated patients with negative second look laparotomy had a survival probability of 100% at 24 months. Irradiated patients with microscopic disease at second look operation had an actuarial 5-year survival of 66%. Patientsd with minimal residual disease at second look laparotomy, receiving consolidation abdominal irrdiation, had an actuarial survival of 5% only at 36 months. It is concluded that consolidation radiotherapy is effective in patients with negative or microscopic residual disease at second-look laparootomy. In regard to bone marrow tolerance split field technique of irradiation is preferred.     

Limb preservation and tumor control in the treatment of popliteal and antecubital soft tissue sarcomas

Soft tissue sarcomas of the antecubital and popliteal space often involve the neurovascular bundle and are prone to recurrence after surgical resection. Amputation has frequently been performed for control of these tumors. A multimodality treatment program consisting of limb-sparing resection, tumor-bed radiation using temporary iridium 192 implants, and adjuvant chemotherapy for high-grade lesions, has yielded satisfactory preservation of limb function and no local tumor recurrence in ten patients after a median follow-up time of 5 years. Eight of the ten patients are still alive, five of whom beyond 5 years; six of the eight survivors had high-grade tumors. These results are superior to those of 14 patients with similar tumors treated earlier by surgery alone: seven by amputation and seven by soft part resection; four of the latter resulted in local recurrence and all of the seven who had high-grade sarcoma died of disease. Multimodality treatment including limb-sparing resection merits consideration in the management of antecubital and popliteal soft tissue sarcomas.     

Preoperative radiation therapy in regionally localized stage III non-small cell lung carcinoma: long-term results and patterns of failure

Seventy-four patients from January 1975 through December 1982, with clinical Stage III Mo non-small cell carcinoma of the lung were treated at our Medical Center with a course of pre-operative radiation therapy to be followed by surgical resection. Radiation therapy consisted of delivering a total dose of 40 Gy with 200 cGy per fraction over a period of 4 weeks to the primary tumor in the lung and the regional lymph nodal areas. Surgical resection was attempted 4 weeks later. Fifty-eight percent of the patients had squamous cell carcinoma whereas the remaining had other histologies like adenocarcinoma, large cell carcinoma, or a combination thereof. All the patients except two were followed up to a minimum of 5 years or until death. Sixty-four patients (82%) had T3 tumors whereas mediastinal nodal involvement was found in 41 patients (55%). Fifteen patients (20%) did not have the operation because of tumor progression, patient's refusal or death. All but two surgically treated patients had tumor resection. Of these 19% had histologically negative specimens, 9 patients (16%) had microscopic disease only, and 37 patients had gross residual disease at the time of surgery. The actuarial 5-year survival and recurrence-free survival rates for the entire group were 20% and 24%, respectively. Patients with a pathologic response had an actuarial recurrence-free survival rate of 53% at 5 years whereas only 17% of those with gross residual disease at surgery had remained recurrence-free at 5 years. One-half of the patients with clinically uninvolved nodes were living recurrence-free at 5 years whereas only 20% of the patients with N2 disease did so. The patterns of failure according to the histology and stage of the disease will be presented.     

Role of brachytherapy in recurrent extremity sarcoma in patients treated with prior surgery and irradiation

The treatment options for recurrent extremity sarcoma following conservative surgery and irradiation are limited. Amputation is the treatment of choice offered for the majority of these patients. In a selected group of patients with recurrent sarcoma, we have investigated the role of brachytherapy along with function-preserving resection. From 1979 to 1988, 40 patients underwent resection and brachytherapy for recurrent extremity sarcoma. There were 23 males and 17 females. All of the patients received function-preserving resection and an afterloading temporary tumor bed implant. A median dose of 4500 cGy was delivered with a range from 3000 to 4800 cGy. The median follow-up was 36 months with a range of 12 to 120 months. The actuarial local control at 5 years is 68%. Five patients (12.5%) developed complications such as wound ulceration (4) and femoral fracture (1) requiring surgery. Five patients developed local failure and an additional two patients had both local and distant failure. All of the failures occurred in patients with more than two prior recurrences. This review suggests that brachytherapy can be used as an effective treatment option in selected patients with recurrent extremity sarcoma following prior surgery and irradiation with satisfactory limb preservation. The data also suggest that higher local control rates can be achieved with early brachytherapeutic intervention.     

The treatment of high-grade soft tissue sarcomas with preoperative thermoradiotherapy

PURPOSE: To explore the use of a novel program of preoperative radiation and hyperthermia in the management of high-grade soft tissue sarcomas (STS). METHODS AND MATERIALS: Eligible patients were adults over 18 with Grade 2 or 3 STS, surgically resectable without a local excision prior to referral to Duke University Medical Center and without distant metastases. Patients were staged generally with CT and/or MR imaging. The diagnosis was established with fine needle aspiration or incisional biopsy. Patients were then treated with 5000 to 5040 cGy, 180-200 cGy per fraction. Chemotherapy was usually not employed. Generally two hyperthermia treatments per week were given with a planned thermal dose of 10-100 CEM 43 degrees T90. Invasive thermometry and thermal mapping were done in all patients. Surgical resection was planned 4-6 weeks after the completion of radiation and hyperthermia. RESULTS: Ninety-seven patients were treated on study between 1984 and 1996. Follow-up ranged from 12 to 155 months (median 32). All tumors were high-grade in nature, 44 greater than 10 cm in size (maximum tumor diameter), 43 5-10 cm in size, 10 less than 5 cm. Seventy-eight of the 97 tumors were located in an extremity. Of the 97 patients, 48 remain alive and continually free of disease following initial therapy. Of the remaining 49 patients, 44 have relapsed (34 dead, 10 living with disease), 3 have died secondary to complications of therapy, and 2 have died of unrelated causes. Ten-year actuarial overall survival, cause-specific survival, and relapse-free survival are 50, 47, and 47% respectively. The predominant pattern of failure has been distant metastases with only 2 patients developing local failure alone. Ten-year actuarial local control for extremity tumors is 94%, 63% for the 19 patients with tumors at sites other than the extremity. Of the 78 patients with extremity lesions, 63 have had limb preservation and remain locally controlled. Overall 38 patients experienced 57 major complications. There were 3 deaths, one due to adriamycin cardiomyopathy and two secondary to wound infections. Four patients required amputation secondary to postoperative wound healing problems. Complications directly attributable to hyperthermia occurred in 15 patients with 11 instances of second- or third-degree burns and two instances of subcutaneous fat necrosis. The hyperthermia complications were generally not severe and either healed readily or were excised at the time of surgical resection of the primary tumor. CONCLUSIONS: For these aggressive high-grade soft tissue sarcomas, this treatment program of preoperative thermoradiotherapy provided excellent local regional control for extremity lesions (95%) and satisfactory local regional control (63%) of nonextremity sarcomas, but did not appear to influence the rate of distant metastases or survival. Complications were frequent but apart from the direct thermal burns, not too different from those reported for preoperative radiotherapy alone. More effective adjuvant systemic therapy is necessary to impact favorably on survival.