Surgical management of retroperitoneal sarcomas associated with external and intraoperative electron beam radiotherapy.

AIMS: To report outcomes of adults with retroperitoneal sarcoma (RS) treated by surgery, external beam radiotherapy (EBRT) and intraoperative electron beam radiotherapy (IORT). METHODS: From July 1988 to February 2001; 24 patients with primary and recurrent RS were diagnosed and treated. The median dose and energy of IORT delivered was 15 Gy/9meV. EBRT dose varies between 45-50 Gy. RESULTS: There were five primary and 19 recurrent tumours. One primary and five recurrent tumours underwent R0 resection. There were 12 liposarcomas and 19 grade I tumours; 13 patients developed local recurrence and three developed distant metastases.Twenty-two patients received IORT associated with EBRT: 11 developed recurrences. Six patients developed Neurotoxicity (4 grade II and 2 grade III). Disease free survival and overall survival at 5 years was 28 and 56% respectively. CONCLUSIONS: EBRT with IORT treatment is a promising technique for local control. Lower recurrence rates are associated with radical (R0) surgical procedures.     

Long-term results of intraoperative electron beam radiotherapy for primary and recurrent retroperitoneal soft tissue sarcoma

PURPOSE: This study assesses the long-term outcome of patients with retroperitoneal sarcoma treated by preoperative external beam radiotherapy, resection, and intraoperative electron beam radiation (IOERT). METHODS AND MATERIALS: From 1980 to 1996, 37 patients were treated with curative intent for primary or recurrent retroperitoneal soft tissue sarcoma. All patients underwent external beam radiotherapy with a median dose of 45 Gy. This was followed by laparotomy, resection, and IOERT, if feasible. Twenty patients received 10-20 Gy of IOERT with 9-15 MeV electrons. These patients were compared to a group of 17 patients receiving preoperative irradiation without IOERT. RESULTS: The 5-yr actuarial overall survival (OS), disease-free survival, local control (LC), and freedom from distant disease of all 37 patients was 50%, 38%, 59%, and 54%, respectively. After preoperative irradiation, 29 patients (78%) underwent gross total resection. For 16 patients undergoing gross total resection and IOERT, OS and LC were 74% and 83%, respectively. In contrast, these results were less satisfactory for 13 patients undergoing gross total resection without IOERT. For these patients, OS and LC were 30% and 61%, respectively. Four patients experienced treatment-related morbidity. CONCLUSIONS: In selected patients, IOERT results in excellent local control and disease-free survival with acceptable morbidity.     

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.     

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.     

Surgical aspects in the treatment of retroperitoneal soft tissue sarcomas

Abdominal soft tissue sarcomas (ASTS) represent a rare malignancy of the abdomen. Diagnosis is often delayed because ASTS tend to be asymptomatic for a long time. Typical clinical symptoms such as pain and augmentation of the abdominal girth develop as a result of the compressing and displacing rather than infiltrating growth pattern of large ASTS. Treatment of patients with ASTS should be managed interdisciplinarily in a tumourboard. Surgery (i.e. wide excision with negative margins) represents the only potentially curative treatment option. Multimodal treatment with radiotherapy and/or chemotherapy, however, is indispensable to reduce the rather high local recurrence rate in these patients despite complete resection. A preoperative core needle biopsy is recommended if diagnosis and hence also therapy are unclear: the biopsy pathway should be chosen in accordance with the surgeon, and the excision has to be performed afterwards within primary surgery. The aggressiveness of surgery is still under debate and ranges from a tissue/organ-sparing approach to an extensive approach with compartmental resection. Thus, the oncologic surgeon must be able to handle complex multivisceral resection as well as extensive vascular reconstruction. Surgery for local recurrence has been shown to be feasible, and the presence of distant metastases usually represents a contraindication for surgery.     

软组织肉瘤手术加术中放疗的临床研究

目的:探讨软组织肉瘤术中放疗的意义。方法:对39例软组织肉瘤患者行根治或姑息性手术,术中放疗在术中放疗手术室进行,术中根据肿瘤大小,选择不同术中放疗限光筒及6～12MeV电子线1次照射15～25Gy,姑息手术者剂量加大至36Gy。术后辅以外照射治疗,常规设野,5/周,2Gy/次,总量40～50Gy。初发病灶10例,术后复发29例。结果:39例患者随访12～64个月,3、5年局控率分别为71.8%和64.1%。3年生存率为82.0%。结论:术中放疗具有较高的局控率,比之其他治疗具有许多优点,将获得较高的生存率。     

软组织肉瘤手术加术中放疗的临床研究

目的：探讨软组织肉瘤术中放疗的意义。方法：对39例软组织肉瘤患者行根治或姑息性手术，术中放疗在术中放疗手术室进行，术中根据肿瘤大小，选择不同术中放疗限光筒及6～12MeV电子线1次照射15～25Gy，姑息手术者剂量加大至36Gy。术后辅以外照射治疗，常规设野，5／周，2Gy／次，总量40～50Gy。初发病灶10例，术后复发29例。结果：39例患者随访12～64个月，3、5年局控率分别为71．8％和64．1％。3年生存率为82．0％。结论：术中放疗具有较高的局控率，比之其他治疗具有许多优点，将获得较高的生存率。     

Multidisciplinary management of soft tissue sarcomas

Musculoskeletal sarcomas are a heterogeneous group of malignant neoplasms derived from connective tissue. Sarcomas represent about 1% of cancer in adults. The annual incidence in adults in Europe is around 14,000 new cases of soft tissue sarcomas (STS) and 4,800 new cases of bone sarcomas. Musculoskeletal tumours arise anywhere in the body, although lower extremities are the most common site of appearance, followed by upper extremities, trunk, retroperitoneum and head and neck area. Adequate management of STS is a stimulating challenge for oncologists. The aim of treatment should be focused on four main aspects: improving survival, avoiding local recurrence, maximising organ function and, finally, minimising morbidity. Surgery, radiotherapy and, sometimes though increasingly, chemotherapy are the pillars on which rests the modern treatment of sarcomas. The optimal management of musculoskeletal tumour requires a multidisciplinary integration of these different approaches in treatment planning right from the initial diagnoses. Referring patients to qualified centres should be desirable to achieve the maximum probability of control and even cure for STS.     

Postoperative radiotherapy in the treatment of extremity soft tissue sarcomas

From 1966 to 1983, 50 patients with extremity soft tissue sarcomas were treated with wide local excision and postoperative radiotherapy at the Mallinckrodt Institute of Radiology. The median follow-up was 70 months (range 28 to 168). Grade was the most significant factor affecting survival: all 11 patients with well differentiated tumor survived versus 6/8 patients with moderate and 17/31 patients with poorly differentiated tumors (p less than 0.01). In addition, lymph node involvement at diagnosis conferred a worse prognosis with only 2/5 patients alive after treatment (p less than 0.05). Eleven of 50 (22%) failed locally. Factors affecting local control included gross residual tumor after operation and limited treatment volume. Among the 35 patients who did not have gross residual tumor or limited treatment volume, two patients who received less than 5000 cGy failed locally versus 1/18 patients who received between 5000-6000 cGy and 2/15 patients who received more than 6000 cGy. Microscopically positive margins and a volume encompassing less than the total muscular compartment was not associated with an increase in the incidence of local failure. Eight patients developed local complication: five due to retreatment for local recurrence. Overall, 24/26 patients who are alive have had their limbs preserved with normal function.     

Pre- or postoperative radiotherapy for soft tissue sarcomas

Sarcomas are rare tumours arising from mesenchymal tissue. A multimodal management in an expert centre combining surgery and radiotherapy is the current standard of care for localized soft-tissue sarcomas of the extremities, to enable limb-sparing strategies. The delivery of pre- radiotherapy or postoperative radiotherapy offers similar local control and survival rates but the toxicity profile is quite different: preoperative radiotherapy increases the risk of wound complications and postoperative radiotherapy affects long-term functional outcomes. While postoperative radiotherapy has long been the rule, especially in Europe, technical improvements with image-guided- and intensity-modulated radiotherapy associated with a better management of postoperative wounds has tended to change practices with more frequent preoperative radiotherapy. More recently the possibilities of a hypofractionated regimen or potentiation by nanoparticles to increase the therapeutic index plead in favour of a preoperative delivery of radiotherapy. The aim of this paper is to report pros and cons of pre- and post-operative radiotherapy for soft-tissue sarcomas.     

Perioperative hyperfractionated high-dose rate brachytherapy combined with external beam radiotherapy in the treatment of soft tissue sarcomas

AIMS AND BACKGROUND: Low-dose rate brachytherapy alone or in combination with external beam radiotherapy represents a well-established adjuvant treatment in soft tissue sarcomas following surgical resection. The experience with high-dose radiotherapy in this indication is limited. The purpose of our study was an evaluation of the viability of perioperative hyperfractionated high-dose rate brachytherapy in combination with external beam radiotherapy for primary and recurrent soft tissue sarcomas. PATIENTS AND METHODS: From February 1998 through June 2002, 10 adult patients with soft tissue sarcomas were treated by interstitial perioperative high-dose rate brachytherapy and external beam radiotherapy. TNM classification was pT2bpN0pM0 in 9 patients and pT1bpN0pM0 in 1 patient. Grade of differentiation was G1 (2 patients), G2 (n = 1), G3 (n = 5), G4 (n = 2). Surgical margins were negative in 7 cases, close in 2 cases and positive in 1 case. The tumor was localized in an extremity in all cases. Hyperfractionation 3 Gy twice daily at 10 mm from the plane of sources was used for brachytherapy, with total doses 18-30 Gy. The patients received external beam radiotherapy with doses 40-50 Gy after brachytherapy. Follow-up periods were between 24-71 months (median, 46). RESULTS: Local control of the disease was achieved in all 10 patients. Distant metastases occurred in 2 cases. One patient was disease free after salvage surgery and chemotherapy, and one patient died of lung disease progression 14 months after brachytherapy. In one case, subcutaneous fistula occurred after radiotherapy and was cured by an excision. Six patients experienced grade 1 or 2 fibrosis and 1 case a mild peripheral neuropathy was recorded. CONCLUSIONS: Our study on a small number of patients suggests that perioperative hyperfractionated high-dose rate brachytherapy with doses 8 x 3 Gy in combination with external beam radiotherapy 40-50 Gy is a promising method to achieve high biological doses in the postoperative radiotherapy of soft tissue sarcomas without severe late morbidity and warrants further research.     

Developments in the management of extremity soft tissue sarcomas

Soft tissue sarcomas, a rare and extremely low prevalence tumor, has no uniform treatment recommendation because there have been few randomized prospective trials to guide management. Recently, there have been surgical, medical, biologic, and genetic advances toward improved treatment. A multidisciplinary approach at specialized treatment centers should be sought because the skill set necessary to implement these advances can be provided and outcomes improved. Centralized care will be crucial to improving survival and functional outcome because it will allow for patients to be effectively entered into prospective randomized trials and create regional and national tissue banks to generate meaningful data.     

Preoperative hypofractionated radiotherapy in the treatment of localized soft tissue sarcomas

BackgroundThe primary treatment of soft tissue sarcomas (STS) is a radical resection of the tumor with adjuvant radiotherapy. Conventional fractionation of preoperative radiotherapy is 50 Gy in fraction of 2 Gy a day. The purpose of the conducted study was to assess the efficacy and safety of hypofractionated radiotherapy in preoperative setting in STS patients.Methods272 patients participated in this prospective study conducted from 2006 till 2011. Tumors were localized on the extremities or trunk wall. Median tumor size was 8.5 cm, 42% of the patients had tumor larger than10 cm, whereas 170 patients (64.6%) had high grade (G3) tumors. 167 patients (61.4%) had primary tumors. Patients were treated with preoperative radiotherapy for five consecutive days in 5 Gy per fraction, with an immediate surgery. Median follow up is 35 months.Results79 patients died at the time of the analysis, the 3-year overall survival was 72%. Local recurrences were observed in 19.1 % of the patients. Factors that had a significant adverse impact on local recurrence were tumor size of10 cm or more and G3 grade. 114 patients (42%) had any kind of treatment toxicity, vast majority with tumors located on lower limbs. 7% (21) of the patients required surgery for treatment of the complications.ConclusionIn this non-selected group of locally advanced STS use of hypofractionated preoperative radiotherapy was associated with similar local control (81%) when compared to previously published studies. The early toxicity is tolerable, with small rate of late complications. Presented results warrant further evaluation.     

Hyperbaric oxygenation in the preoperative radiotherapy of soft tissue sarcomas]

Based on the study of clinical and morphological criteria for estimation of the efficacy of distance gammatherapy under hyperbaric oxygenation in the combined treatment of patients with soft tissue sarcomas, it was concluded that hyperbaric oxygenation employed in radiotherapy contributed to the increased rate of neoplasms damage. The latter resulted in a decreased percentage of the recurrence. The attenuation of local radiation and less number of postoperative complications indicate that healthy tissues surrounding the tumor are preserved. No rise in the percentage of distant metastases was noted in irradiation under hyperbaric oxygenation.     

Local management of adult soft tissue sarcomas

Soft tissue sarcomas (STS) are rare tumors classified into multiple histological subtypes and categorized into four sites: extremity and trunk, head and neck, retroperitoneal, and visceral, the latter now predominantly consisting of gastrointestinal stromal tumors. Well-planned, complete surgical resection is the mainstay of curative therapy for tumors at each of these sites. The success of surgery alone in controlling disease varies with the site, histologic grade, depth, and size of the tumor. For high-risk tumors, adjuvant therapy should be considered. In high-risk extremity tumors, adjuvant radiation has been proven in randomized trials to improve local control. Limb-sparing surgery combined with adjuvant radiation achieves equivalent local control to amputation, with the same distant relapse-free survival. Due to anatomical constraints, tumors of the head and neck and retroperitoneum are typically excised with close margins, providing a rationale for adjuvant radiation; the available evidence suggests but does not prove a benefit. Large-scale trials of adjuvant imatinib for gastrointestinal stromal tumors are currently being conducted. For tumors of the extremity/trunk, head and neck, and retroperitoneum, biopsy prior to definitive resection is recommended to establish the diagnosis and permit intelligent treatment planning with appropriate choice and sequencing of adjuvant therapies. This planning is most expeditiously done through multidisciplinary consultation at an experienced sarcoma center.     

Response of canine esophagus to intraoperative electron beam radiotherapy

Tolerance of esophagus to intraoperative radiotherapy (IORT) was investigated in dogs. Thirteen adult foxhounds were subjected to right thoractomy, mobilization of the intrathoracic esophagus, and IORT to a 6 cm full-thickness esophageal segment using 9 MeV electrons at doses of 0, 2,000, or 3,000 cGy. Dogs were followed clinically and were evaluated at regular intervals after treatment with fiberoptic esophagoscopy, barium swallows, and postmortem histologic evaluations. One sham-irradiated control dog showed no abnormalities during follow-up of 24 months. Seven dogs receiving 2,000 cGy IORT showed transient mild dysphagia and mild esophagitis, but no clinically or pathologically significant complications. Five dogs receiving 3,000 cGy demonstrated severe ulcerative esophagitis within 6 weeks of treatment which progressed to chronic ulcerative esophagitis with stricture formation by 9 months following IORT. One 3,000 cGy dog died at 13 months from an esophageal perforation. On the basis of a pilot experience using 13 experimental animals, it was concluded that intact canine esophagus tolerates IORT well to doses of 2,000 cGy, but doses of 3,000 cGy pose serious and potentially lethal risks. The clinical application of IORT to the treatment of human intrathoracic neoplasms requiring esophageal irradiation should be approached with caution, particularly at doses exceeding 2,000 cGy.     

Low-dose intraoperative brachytherapy in soft tissue sarcomas involving neurovascular structure.

BACKGROUND AND PURPOSE: To evaluate intraoperative brachytherapy in the management of soft tissue sarcomas involving neurovascular structures, its impact on local control and complications. PATIENTS AND METHODS: Between 01/1989 and 12/2002, 98 patients received an intraoperative implant in conjunction with conservative surgery. Brachytherapy was part of the initial treatment (79 cases) or performed in recurrent disease (19 cases). We studied primary sarcomas involving neurovascular structures treated with conservative surgery and intraoperative brachytherapy (n = 6) or intraoperative brachytherapy and external irradiation (n = 73). Conservative surgery was performed as first treatment (51 cases), after chemotherapy (21 cases) and after primary external radiation (seven cases). Brachytherapy was performed according to Paris system rules. Patients were loaded with Iridium 192 (64 cases) or connected to a Microselectron PDR (15 cases). Mean dose given by brachytherapy was 20 Gy. Mean dose given of external radiotherapy was 46 Gy. RESULTS: With a median follow-up of 58 months, 5-year actuarial survival was 69% and local free disease at 5 years was 90%. Acute side-effects occurred in 22/79 requiring surgical repair in 10 patients. Late side-effects occurred in 35/79. No patient required amputation for complications. Prognostic factors were studied for the occurrence of acute and late side-effects and local control. CONCLUSIONS: Intraoperative brachytherapy is efficient with excellent local control rates in soft tissue sarcomas presenting with neurovascular involvement and offers an acceptable conservative option.