Hypofractionated Preoperative Radiotherapy for High Risk Soft Tissue Sarcomas in a Geriatric Patient Population

BackgroundStandard therapy for localised, resectable high risk soft tissue sarcomas consists of wide excision and radiotherapy over several weeks. This treatment schedule is hardly feasible in geriatric and frail patients. In order not to withhold radiotherapy from these patients, hypofractionated radiotherapy with 25 Gy in 5 fractions was evaluated in a geriatric patient population.Patients and methodsA retrospective analysis was performed of 18 geriatric patients with resectable high risk soft tissue sarcomas of extremities and thoracic wall. Wound healing and short term oncologic outcome were analysed. In addition, dose constraints for radiotherapy of the extremities were transferred from normofractionated to hypofractionated radiotherapy regimens.ResultsFeasibility was good with 17/18 patients completing treatment as planned. Wound healing complication rate was in the range of published data. Two patients developed local and distant recurrence, two patients isolated distant recurrences. No isolated local recurrences were observed. Keeping the constraints was possible in all cases without compromising the coverage of the target volume.ConclusionsHypofractionated radiotherapy and surgery was well tolerated even in this specific patient population. With feasibility concerning early wound healing problems and adapted constraints, which allow for the treatment of most resectable extremity tumours, the concept warrants further evaluation in patients unfit for standard radiotherapy.Key words: sarcoma, radiotherapy, preoperative, geriatric patients, wound healing, hypofractionation     

Low dose-rate interstitial brachytherapy in soft tissue sarcomas

Purpose. To assess the effectiveness of Ir-192 interstitial brachytherapy as an adjunct to wide local excision as a functionsaving strategy for soft tissue sarcomas.Subjects and methods. From September 1993 to April 1998, 20 consecutive patients diagnosed with soft tissue sarcomas were treated with a combination of wide local excision and interstitial brachytherapy. In 16 patients brachytherapy was done as an intraoperative procedure, while in four, the implant was performed post-operatively under local anesthesia. Eleven of the 20 patients also received external beam radiotherapy following the implant.Results. After a mean follow-up of 27 months (4-54) the local control rate for all 20 patients was 85% (17/20). In the 16 patients who had an intra-operative implant, local control was 94% (15/16). In the four patients who underwent a post-operative implant, local control was 50% (2/4). Actuarial 5-year survival was 90%. There were three cases (15%) of severe local complications.Conclusions. Wide local excision followed by low dose rate intersitital brachytherapy have yielded a 85% local control rate in 20 patients with soft tissue sarcomas. Local control rates were higher when the implants were done as an intra-operative procedure than as a post-operative one.     

Flap reconstruction and interstitial brachytherapy in nonextremity soft tissue sarcoma

Radiotherapy is an integral component of management of high-grade soft tissue sarcomas. Interstitial brachytherapy is used to deliver a boost or radical dose with several advantages over external beam radiotherapy. There has always been a concern to use brachytherapy with flap reconstruction of skin defects after wide excision. We preset our initial experience with interstitial brachytherapy in two patients of recurrent high-grade non-extremity sarcomas treated with surgical excision and soft tissue reconstruction of surgical defect.     

Wound complications are a predictor of worse oncologic outcome in extremity soft tissue sarcomas

BackgroundIn various oncological conditions, complications correlate with diminished prognosis, however literature on soft tissue sarcomas is limited and inconclusive. The aim of this study was to assess risk factors and the oncologic impact of wound complications in primary extremity soft-tissue sarcomas.MethodsPatients with primary extremity soft tissue sarcomas without dissemination and with clear surgical margins (R0) were analyzed. Groups with and without wound complications were compared by univariate and multivariable analysis to identify risk factors. Uni- and multivariable analysis of factors associated with local recurrence free survival (LRFS), metastasis free survival (MFS) and disease specific survival (DSS) were performed.Results682 patients were included in the study, wound complications occurred in 94 patients (13.7%) within 90 days. Age, ASA-stage, high tumor size and grade, tumor location in the foot, neoadjuvant radiation therapy and operation time represented independent risk factors for wound complications. Patients with wound complications had a significantly worse estimated 5-year LRFS of 49.4 ± 6% versus 78.3 ± 2.1% and 5-year DSS of 77.9 ± 5.4% versus 89.1 ± 1.6%. Wound complications could be identified as an independent risk factor for worse LRFS (HR 2.68[CI 1.83–3.93], p < 0.001) and DSS (HR 1.79[CI 1.01–3.16], p = 0.046).ConclusionWound complications after soft tissue sarcomas of the extremities are associated with worse local oncological outcome and survival. Patients with high risk of wound complications should be identified and strategies implemented to reduce surgical complications and possibly improve oncologic prognosis.     

Preoperative vs postoperative radiation therapy for extremity soft tissue sarcoma: controversy and present management

PURPOSE OF REVIEW: The 5-year results of the Canadian multicenter prospectively randomized phase III trial that compared preoperative with postoperative radiotherapy for patients with extremity soft tissue sarcomas were recently presented at the 2004 meeting of the American Society of Clinical Oncology. These latter findings serve as an impetus for this current review to assess the optimal sequencing of adjuvant radiotherapy for such patients undergoing limb-preserving surgery. RECENT FINDINGS: The recent studies, including the 2004 American Society of Clinical Oncology presentation, described in this paper show no significant rise in the incidence of long-term side effects, such as delayed wound healing and subcutaneous tissue damage, in patients with extremity soft tissue sarcomas who receive once-daily preoperative irradiation followed by limb-preserving surgery. Postoperative radiotherapy may be best reserved for patients who are most likely to undergo a wide local excision with adequate (>10 mm) tumor-free margins (such as low-grade lesions in the lower extremities). There is an increasing use of neoadjuvant chemoradiation in this group of patients, especially for high-grade and large lesions. SUMMARY: Further investigations regarding the preoperative management of extremity soft tissue sarcomas are continuing in an attempt to optimize the survival and functional status of these patients, while minimizing the permanent side effects resulting from such treatment.     

软组织肉瘤局部切除加组织间照射治疗──附10例报告

１０例侵犯主要血管、神经和骨的肢体局部晚期软组织肉瘤，经局部切除加后装放射治疗并随访６～２４个月，除１例因肺、脑转移死亡，１例肺转移带瘤生存外，余８例均无局部复发或远处转移，仅１例切口延迟愈合。作者介绍了瘤床置管、后装（１９２）铱放射治疗的方法和注意事项，认为该法可有效控制局部晚期软组织肉瘤复发，并能较满意保留肢体功能。     

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。     

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.     

Optimizing radiation therapy and post-treatment function in the management of extremity soft tissue sarcoma

Opinion statement When treating soft tissue sarcomas (STS) of the extremities, the major therapeutic goals are survival, local tumor control, optimal function, and minimal morbidity. Surgical resection of the primary tumor is the essential component of treatment for virtually all patients. However, local control by surgery alone is poor for the majority of patients with extremity lesions unless the procedure removes large volumes of grossly normal tissue (ie, widely negative margins are attained, because sarcomas tend to infiltrate normal tissue adjacent to the evident lesion). Thus, removal of the gross lesion by a simple excision alone is followed by local recurrence in 60% to 90% of patients. Radical resections reduce the local recurrence rate to 10% to 30%, but may compromise limb function. The combination of function-sparing surgery and radiation achieves better outcomes than either treatment alone for nearly all patients with STS. Because both surgical and radiation technique are critically important for optimizing local control of tumor and functional outcome, it is important to manage these patients in dedicated multispecialty clinics comprised of physicians with expertise in sarcomas, including orthopedic and general oncologic surgeons, radiation oncologists, medical oncologists, sarcoma pathologists, and bone and soft tissue diagnostic radiologists. Radiation therapy can be given by external beam radiation therapy (EBRT) or brachytherapy (BRT) or combination thereof. External beam radiation can be given either preoperatively or postoperatively. The clinical considerations and the outcome data that must be considered in choosing the most appropriate treatment technique for the individual patient are discussed.     

The influence of anatomic location on outcome in patients with soft tissue sarcoma of the extremity

BACKGROUND: The anatomic location of an extremity soft tissue sarcoma may influence the patient's presentation, management, and local and systemic recurrence rates. The objective of this study was to compare the presentation, management, and outcome of patients with soft tissue sarcomas of the upper extremity and the lower extremity. METHODS: Prospectively collected data from patients who underwent limb-sparing surgery for extremity soft tissue sarcoma between January, 1986 and April, 1997 were analyzed. Local recurrence free rates and metastasis free rates were calculated using the method of Kaplan and Meier. Univariate and multivariate analyses of potential predictive factors were evaluated with the log-rank test and the Cox proportional hazards model. RESULTS: Of 480 eligible patients, 48 patients (10.0%) had a local recurrence, and 131 patients (27.3%) developed distant metastasis. The median follow-up of survivors was 4.8 years (range, 0.1-12.9 years). Patients with upper extremity tumors had smaller lesions (6.0 cm vs. 9.3 cm; P < 0.001), more often underwent unplanned excision before referral (89 patients [64.0%] vs. 160 patients [46.9%]; P < 0.001), and less often received radiotherapy (98 patients [70.5%] vs. 289 patients [84.8%]; P < 0.001). The 5-year local recurrence free rate was 82% for patients with sarcomas of the upper extremity and 93% for patients with sarcomas of the lower extremity (P = 0.002). The 5-year metastasis free rate was 82% for patients with sarcomas of the upper extremity and 69% for patients with sarcomas of the lower extremity (P = 0.013). CONCLUSIONS: Local recurrence was more frequent in patients who had sarcomas of the upper extremity compared with patients who had sarcomas of the lower extremity. Factors that contributed to this difference included histologic type, the use of radiotherapy, and local anatomy. Metastasis was more frequent among patients with sarcomas of the lower extremity, because those tumors tended to be large and deeper compared with upper extremity tumors.     

Combined-modality treatment of localized soft tissue sarcomas of the extremities

Over the past 20 years, considerable progress has been made in the treatment of patients with extremity soft tissue sarcomas. There has been a migration away from amputation toward treatment by excision plus radiation for most patients with localized tumors. Decisions about the optimal use and sequencing of surgery and radiation remain complex. Whereas it is clear that local control is probably not impacted significantly by the treatment sequence, rates of wound complication, fibrosis, and edema are affected by the treatment sequence. In addition, recent single-institution reports indicate that some carefully selected patients can be treated by surgery alone. The recent data evaluating treatment by surgery alone and treatment sequencing variables do not lead to a situation in which clear, uniform recommendations for treatment can be made for many patients with extremity soft tissue sarcomas. Indeed, treatment planning for patients with extremity soft tissue sarcoma in the new millennium is infinitely more complex than it was in the era when amputation was the primary treatment for these patients. Considerable clinical experience and multidisciplinary input are required for optimal treatment planning for these patients. Future research should be directed at refining the indications for specific therapies, reducing the toxicities of local therapies, and developing more effective systemic therapies.     

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.     

Feasibility of limb salvage and survival in soft tissue sarcomas

One hundred nine consecutive patients with soft tissue sarcomas were treated in the period 1977 through 1983. Of 85 patients with extremity sarcomas, only 3 patients (4%) were managed with amputation, whereas in the previous decade, 40% of such patients were treated with amputation in our institute. The current 5-year survival rate is 63%; in the previous decade it was 45%. In the current series, for extremity locations, patients with minimum surgical margins of 2 cm or greater and no further local therapy had a 5-year local recurrence rate of 17%, whereas those with minimum surgical margins of less than 2 cm and who were treated with adjuvant postoperative radiation had a local recurrence rate of 7%. In the previous period, the local recurrence rate was 30% after wide resection and 66.6% after local excision. With a combination of modalities, limb salvage can be practiced currently in the majority of patients with extremity soft tissue sarcomas without any adverse effect on recurrence rates and survival.     

Extremity preservation by combined modality therapy in sarcomas of the hand and foot: an analysis of local control, disease free survival and functional result

A primary tumor arising in the hand or foot represents an uncommon presentation for patients with Ewing's sarcoma (ES) or soft tissue sarcoma (STS). While there exists considerable literature on the treatment of extremity sarcomas, very little deals specifically with lesions of the hand or foot. It remains controversial whether these lesions can be successfully treated with combined modality therapy which preserves the extremity and maintains function. From 1972 to 1979, 10 patients with sarcomas arising in the hand or foot were treated with combined modality therapy at the National Cancer Institute. Seven patients with ES of bone received local irradiation to 5000 rad and combination chemotherapy following an incisional biopsy. Three patients with STS received a gross tumor excision and local irradiation to 6000 rad. One STS patient also received combination chemotherapy. Local control was achieved in nine patients (90%) with a follow-up of 30-119 months (median 56 months). These patients have complete or almost complete function of the treated extremity. Nine patients are alive with five patients remaining disease-free following the initial combined modality treatment. Two patients with Ewing's sarcoma relapsed (1 patient with both local and distant failure) at 26 and 58 months and were again rendered disease-free with surgery, total body irradiation and further chemotherapy. One patient relapsed for a second time, being disease-free from the first relapse for 30 months. We conclude that for selected patients with sarcomas arising in the hand or foot, combined modality therapy which leaves the extremity intact results in excellent local tumor control and preserves function. Careful treatment planning is an essential aspect of successful radiation therapy of a hand or foot primary. Our treatment recommendations are outlined. This approach is a viable alternative to amputation in these patients.     

Sarcomas of soft tissue and bone

Sarcomas arise primarily from mesenchymal structures at any site in the body, even within visceral stroma and neurovascular bundles. Sarcomas have been associated with prior radiation therapy, toxic exposures, and genetic conditions and soft tissue sarcomas have been distinguished from bone sarcomas. For localized soft tissue sarcoma, tumor grade is the most important prognostic variable. Low-grade tumors are generally cured by wide surgical excision, but there is a significant rate of both local recurrence and development of distant metastasis in high-grade lesions. The treatment of soft tissue sarcoma histologic subtypes is generally similar grade-for-grade, with the exception of rhabomyosarcoma, Kaposi's sarcoma, and mesothelioma. Tumor location strongly influences resectability. Radiation therapy has been used successfully in conjunction with conservative surgery to improve local control rates for soft tissue sarcomas, particularly in extremity lesions. Currently, adjuvant chemotherapy remains unproven for most adult soft tissue sarcomas, but is established in the treatment of rhabdomyosarcomas, osteosarcomas, and Ewing's sarcomas.     

Intracranial ganglioglioma WHO I: results in a series of eight patients treated with stereotactic interstitial brachytherapy

In this retrospective study we evaluated the efficacy of interstitial brachytherapy (IBT) using ¹²⁵Iodine seeds (¹²⁵I) for intracranial ganglioglioma WHO I. Between October 1994 and March 2010, eight patients (m/f = 5/3, median age 30.4 years, age range 7–42.5 years) with intracranial ganglioglioma WHO I were treated with IBT using stereotactically implanted ¹²⁵I seeds. The median follow-up time was 41.5 months (range 16.7–140.1 months). Prior to interstitial brachytherapy one patient underwent microsurgical resection for three times; seven patients were treated with IBT primarily. In all patients we implanted the ¹²⁵I seeds stereotactically guided. The cumulative tumor surface dose ranged between 50 and 65 Gy (permanent implantation) and the median tumor volume was 5.6 ml (range 0.9–26 ml). After brachytherapy, follow-up MR imaging revealed complete remission in one patient, partial remission in three and stable disease in the remaining four patients. Five of eight patients presented with seizures were either seizure-free (1/5) or improved (4/5). Temporary treatment-related morbidity occurred in one patient only (headache, nausea/vomiting) and resolved completely under steroid medication after 4 weeks. No treatment-related mortality was observed. This study indicates that interstitial brachytherapy for the treatment of intracranial ganglioglioma WHO I is safe and provides a high rate of local tumor control. Due to the limited number of cases, it is not possible to conduct a rigorous statistical evaluation. Thus, larger numbers of patients are required.     

High incidence of metastatic disease in primary high grade and large extremity soft tissue sarcomas treated without chemotherapy

Background  

The risk of metastasis and the survival in patients with primary extremity soft tissue sarcomas is worse when tumour size is large and the grade of malignancy is high. Such tumours may receive chemotherapy and/or radiation therapy (RTX) for optimising local control. Irradiation can either be applied preoperatively or after tumour resection. The question arises if the kind of RTX in the absence of chemotherapy influences the outcome concerning local control, metastatic disease, survival and complications.     

Radiotherapy and hyperthermia with curative intent in recurrent high risk soft tissue sarcomas

Purpose: Radiotherapy before or after resection is one of the pillars of treatment for localised high risk soft tissue sarcomas. Treatment intensification has been described with concurrent chemotherapy and hyperthermia. The aim of this study is to assess local control after multimodal treatment, focussing on the treatment of local recurrences after surgery only.

Patients and methods: Of 42 patients treated in a prospective protocol with radiotherapy and hyperthermia, nine were treated for isolated local recurrences without metastatic spread. Most patients were treated with trimodal therapy including chemotherapy with ifosfamide and underwent resection whenever possible. Median follow-up was 1.4?years.

Results: The treatment was well tolerated. Estimated disease free survival, distant metastases free survival and local control for the whole cohort after 1.5?years were 66, 73 and 88%, respectively. Neoadjuvant vs. adjuvant treatment influenced local control with a trend to statistical significance. Resection status did not influence local control. The cohort of patients treated for local recurrence after surgery alone had a significantly impaired local control compared to multimodal treatment at primary diagnosis (100 vs. 52%, p?Conclusions: With multimodal therapy including radiotherapy and hyperthermia local tumour control is achievable even in locally recurrent tumours. The clear-cut difference of the treatment of local recurrence in contrast to primary diagnosis might either reflect difficulties in diagnosis and treatment of local recurrences or biological aggressiveness of recurrent tumours. However, we recommend to consider multimodal treatment at primary diagnosis of high risk soft tissue sarcomas.     

An improved operative technique for placement of brachytherapy catheters in treatment of soft tissue sarcomas

Two patients with malignant soft tissue sarcomas were treated with local excision followed by a combination of brachytherapy and external beam radiation therapy. The involved areas were large resulting in extensive and irregular sites of resection. The individual placement of multiple brachytherapy catheters in such large, irregular contours can be a time-consuming and technically difficult task often resulting in an uneven distribution of the catheters within the sites of resection. We therefore describe a technique of catheter distribution.     

肢体软组织肉瘤34例外科治疗体会

目的探讨肢体软组织肉瘤的诊断与手术疗效。方法回顾性分析外科手术治疗并经病理证实的34例肢体软组织肉瘤患者的诊治资料。结果术后病理:韧带样瘤型纤维瘤病4例,纤维肉瘤5例,浅表型纤维瘤病1例,隆突性皮肤纤维肉瘤4例,恶性纤维组织细胞瘤4例,脂肪肉瘤5例,平滑肌肉瘤5例,恶性周围神经鞘膜瘤2例,滑膜肉瘤2例,原始神经外胚层瘤2例。28例获术后随访1～4 a,4例(14.3%)复发,复发时间12～26个月,平均20个月。结论外科手术是肢体软组织肉瘤最重要的治疗手段,合理应用综合治疗和个体化治疗可提高切除率、降低复发率。