Adult Pelvic Sarcomas: A Heterogeneous Collection of Sarcomas?

Introduction. Adult pelvic soft tissue sarcomas are a rare group of heterogeneous malignancies. These sarcomas differ from extremity and trunk soft tissue sarcomas in presentation, characteristics and response to treatment.Methods. A retrospective analysis of patient and tumor characteristics, treatment and prognosis and prognostic factors was performed.Results. Between 1977 and 1997, a total of 33 adult patients with soft tissue sarcomas involving the pelvis but excluding uterine leiomyosarcoma were identified. Leiomyosarcomas (18), including six GIST, and rhabdomyosarcomas (eight) were the most commonly seen tumors. At first presentation, nine patients already had metastases. The mean follow-up was 52 months (1-200). Recurrences developed in 15 of the 24 cases (63%) with tumors without metastases at first presentation; in six (25%) recurrence was locally only, in nine distant metastases occurred. The nine patients with metastatic disease at first presentation died of the disease, while eight of the 24 patients with localized disease at presentation died. One patient died of an unrelated cause, four were alive with disease, and 11 patients were alive and free of disease. The only identifiable prognostic factor of disease-free interval and overall survival was histological grade.Conclusion. Soft tissue sarcomas of the pelvis appear to be associated with increased rate of metastasis at the time of diagnosis and higher rates of local recurrence. In this study, multi-modality treatment for most primary tumors did not show a significant benefit in recurrence rate, DFI and OST, when compared to single modality approach. Although the number of patients in this study is small, and different types of sarcomas were studied, the only identifiable predictor for survival was low histological grade of the tumors. The differences of this heterogeneous group of pelvic sarcomas with retroperitoneal, trunk and extremity sarcomas should be taken into consideration in the management of these sarcomas.     

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.     

屏障切除术治疗复发性软组织肉瘤的疗效分析

目的：评价屏障切除术治疗复发性软组织肉瘤（STS）的疗效。方法：对81例复发性STS行屏障切除术。27例术中切缘再确认。修复重建73例。手术＋放疗＋化疗3例;手术＋放疗3例;手术＋化疗10例。1例术前隔离热药灌注。结果：术中切缘阳性2例,占7.4%。随访时间平均30个月（12～138个月）,复发13例,占16.0%。屏障切除后的平均复发时间较前次延长18个月。结论：屏障切除术复发率明显低于广泛切除术。     

Management of pelvic sarcoma

Pelvic sarcomas are a rare and heterogenous group of tumors divided into two groups: soft tissue sarcomas and bone sarcomas. Soft tissue sarcomas of the pelvis include most commonly liposarcoma, leiomyosarcoma, gastrointestinal stromal tumors, malignant peripheral nerve sheath tumors, and solitary fibrous tumors. Bone sarcomas of the pelvis most commonly include osteosarcoma and chondrosarcoma. Multidisciplinary treatment at a center experienced in the treatment of sarcoma is essential. Management is dictated by histologic type and grade. Surgical resection with wide margins is the cornerstone of treatment for pelvic sarcomas, although this is often challenging due to anatomic constraints of the pelvis. Multimodal treatment is critical due to the high risk of local recurrence in the pelvis.     

New Developments in Targeted Therapy for Soft Tissue Sarcoma

Soft tissue sarcomas (STS) are rare diseases, with an estimated 10,390 new cases in the United States in 2008. Unfortunately, only 50% are cured with surgical resection. The standard cytotoxic chemotherapeutic agents have not been successful in the treatment of metastatic disease. The standard single-agent chemotherapy for metastatic disease is doxorubicin, with only 20% to 25% response rates. The combination of doxorubicin with other agents, such as ifosfamide, has improved response rates, without any improvement in overall survival. New targeted therapies have shown some activity in STS; however, disease stabilization is seen more often than a true radiographic response. The combination of cytotoxic chemotherapy with more targeted and novel agents may be appropriate to improve outcome in these patients. The agents of interest in sarcomas at this time are multi-tyrosine kinase inhibitors, antiangiogenesis agents, inhibitors of mammalian target of rapamycin, hypoxia-activating prodrugs, insulin growth factor monoclonal antibodies, and tumor necrosis factor-related apoptosis-inducing ligand agonists.     

Soft-tissue sarcomas in children and adolescents with neurofibromatosis type 1

BACKGROUND: Patients affected by neurofibromatosis type 1 (NF1) are at higher risk of developing soft-tissue sarcomas (STS) than the general population. The clinical findings and outcome in 43 children and adolescents with NF1 treated for STS in the Italian protocols between 1988 and 2004 are reported. METHODS: The study included 37 patients with neurogenic sarcomas (36 malignant peripheral nerve sheath tumors [MPNST], 1 triton tumor) and 6 cases of rhabdomyosarcoma (RMS). The prevalence of NF1 observed during the study period was 43% in the MPNST population and 1% in the RMS group. RESULTS: Most patients with neurogenic sarcomas had large, invasive tumors. Five-year event-free and overall survival rates were 19% and 28%, respectively. Two of 16 patients with evaluable disease responded to chemotherapy. All 6 RMS patients were 相似文献   

Isolierte Extremitätenperfusion zur lokalen Tumorkontrolle an den Gliedmaßen

Clear and wide safety margins are required in surgical resections of high-grade soft tissue sarcomas (STS) due to the proliferation patterns at the periphery of the tumors. But resections of large and deep-seated tumors are often limited by close or even marginal resection margins in order to salvage a limb and its function. Hence, neoadjuvant treatment strategies may improve subsequent surgical resection by shrinking and devitalizing the local tumor. Of these treatment modalities, hyperthermic isolated limb perfusion with TNF-α and melphalan (TM-ILP) provides the most effective deterioration of advanced and even nonresectable STS by immediate destruction of the vasculature. Different studies have reported remission rates of up to 80%, with improved subsequent resection as well as minimization of the surgical trauma usually associated with the resection of high-grade sarcomas. Obviously, TM-ILP has its greatest potential in advanced STS of the limbs with concomitant metastatic disease. Patients are ready for systemic treatment strategies within days of deterioration of the local tumor by TM-ILP. This treatment modality should be offered to these patients and should be available in tertiary cancer centers.     

Retroperitoneal soft tissue sarcoma: effect of hyperthermic total abdominal perfusion

AIMS AND BACKGROUND: Soft tissue sarcomas (STS) of the retroperitoneum are rare tumors. Surgery remains the principal modality of therapy in the management of primary and recurrent retroperitoneal STS. However, little is known about the effect of regional chemotherapy using hyperthermic total abdominal perfusion (HTAP). We analyzed independent prognostic variables in 33 patients with STS in the retroperitoneum admitted from November 1990 through December 1996. METHODS AND STUDY DESIGN: Data regarding patients' age, gender, tumor size, histological tumor type, tumor location, type of operation (primary or secondary surgery), extent of surgical management (marginal or extended), use of HTAP, tumor grade, and tumor stage according to the TNM classification were examined by univariate and multivariate analyses. RESULTS: All 33 patients underwent complete resections (marginal or extended). Eleven of them received locoregional chemotherapy by HTAP. The overall cumulative 5-year survival rates in patients with stage IIA and advanced disease were 82% and 22%, respectively (log-rank test, P<0.01). Using Cox's proportional hazard model, tumor stage, use of HTAP and type of operation were found to have significant influence on overall survival (P<0.05). CONCLUSIONS: Our results showed that complete resection along with HTAP chemotherapy may improve survival in patients with retroperitoneal STS. These phase II data could be used to support the initiation of a phase III trial to test HTAP in patients submitted to complete resection of retroperitoneal STS.     

软组织肉瘤化疗新药临床研究进展

软组织肉瘤是一组来源于间叶组织的恶性肿瘤,目前的治疗仍是以手术为主的综合治疗,手术后约50%的患者可能发生远处血行转移。虽然局部放疗可以减少部分患者术后局部复发,但是化疗是综合治疗的重要组成部分,对于降低肿瘤局部复发和减少远处转移、提高患者生存率和改善生活质量有积极作用。     

软组织肉瘤化疗新药临床研究进展

软组织肉瘤是一组来源于间叶组织的恶性肿瘤,目前的治疗仍是以手术为主的综合治疗,手术后约50%的患者可能发生远处血行转移。虽然局部放疗可以减少部分患者术后局部复发,但是化疗是综合治疗的重要组成部分,对于降低肿瘤局部复发和减少远处转移、提高患者生存率和改善生活质量有积极作用。     

臀部恶性和侵袭性软组织肿瘤的外科治疗

目的探讨臀部软组织肉瘤屏障切除和臀部肿瘤分区修复的可能性和效果。方法1992年7月至2004年1月收治臀部肿瘤中资料完整15例，男6例，女9例。年龄16～71岁，平均44．3岁。软组织肉瘤12例中，11例采用屏障切除方法切除肿瘤，另4例行边缘切除或经瘤切除。9例作了11块肌皮瓣覆盖缺损。2／15例重建了动力功能。结果软组织肉瘤屏障切除随访时间6—96个月，平均34．5个月。其中2例复发，复发率18．1％，平均复发时间33个月。4例平均术后13个月死亡，屏障切除占2例。11块肌皮瓣中1例坏死20％，余全部成活。结论屏障切除术是软组织肉瘤切除的理想术式，适应证比根治性切除术更广，复发率低于广泛切除术，而可操作性优于广泛切除术。臀部缺损的划区肌皮瓣修复方法简单，成功率高。     

Patterns of care in a population‐based sample of soft tissue sarcoma patients in the United States

BACKGROUND:

Soft tissue sarcomas (STS) are relatively uncommon tumors. Data regarding the patterns of care of patients with STS and its consistency with available guidelines are relatively sparse. The authors conducted a detailed analysis of STS patients diagnosed in 2002 and sampled from the Surveillance, Epidemiology, and End Results registries.

METHODS:

The authors sampled 1369 patients with invasive sarcomas. Hospital records were reabstracted, and treating physicians were contacted to verify the therapy provided to each patient.

RESULTS:

The median age of patients was 60 years. There was a slight male predominance among the patients with nongynecologic sarcomas. Fifty percent of the patients had localized stage sarcoma. Most patients received surgery, but negative margins were obtained in only 50% of patients. Complete resection was less frequent in patients ≥50 years old. Radiation therapy was used in 53% of patients with extremity sarcomas but in only 20% to 30% of the patients with sarcomas at other sites. About 27% of all patients received chemotherapy. Tumor grade was significantly associated with the use of radiation and chemotherapy. Surgical resection, tumor grade, tumor size, use of radiation therapy, and age significantly influenced survival.

CONCLUSIONS:

Patterns of care of STS differ based on the site of the tumor. The patterns of care for extremity sarcomas are fairly consistent with the available recommendations, but the patterns of care for other sites are less consistent. In addition to certain tumor characteristics, age of the patient was significantly associated with therapy and patient outcome. Cancer 2009. © 2009 American Cancer Society.     

Metastases to the retroperitoneum in patients with extremity soft tissue sarcoma: an unusual metastatic pattern

BACKGROUND: Extremity soft tissue sarcoma (STS) metastasizes preferentially to the lungs via the hematogenous route. Metastases in extrapulmonary sites such as bone, brain, and subcutaneous tissues are observed less frequently. To the authors' knowledge, limb STS primarily metastasizing to the retroperitoneum has not been described to date. The current study reviews the clinical course, management, and patient prognosis in such a pattern of metastasis. METHODS: Records of patients with retroperitoneal metastases originating from an extremity STS between 1994-1998 were reviewed. Patient demographics, primary tumor site, other tumor sites, local recurrence, distant metastasis, treatment, and survival were analyzed. RESULTS: Ten patients were included in the study. All had primary STS of different histologic types and high histologic grade confined to a lower limb. The retroperitoneal metastases were diagnosed between 6-120 months (mean, 45 months) after diagnosis of the primary sarcoma. At that time, one patient had evidence of local recurrence of the primary tumor site, two patients had lung metastases, and one patient had diffuse bone metastases. Eight patients were eligible for surgery. In six of these patients the metastases were excised completely. The median follow up was 12 months. Of the six patients who underwent complete resection, 3 were alive at last follow-up with no evidence of disease after 12 months, 14 months, and 24 months, respectively. Two patients with recurrent retroperitoneal disease and one patient with retroperitoneal and lung metastases died despite systemic chemotherapy. CONCLUSIONS: Extremity STS can metastasize hematogenously to the retroperitoneum, a fact that mandates a high index of suspicion and abdominal imaging studies during the follow-up of such patients. Retroperitoneal metastases necessitate aggressive surgical resection to enable prolongation of survival.     

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.     

Intraoperative radiotherapy electron boost followed by moderate doses of external beam radiotherapy in resected soft-tissue sarcoma of the extremities.

PURPOSE: To analyze the patterns of failure and the toxicity profile of intraoperative electron beam radiotherapy (IOERT) after resection of soft tissue sarcomas of the extremities (STS). PATIENTS AND METHODS: Forty-five patients with extremity STS were treated with IOERT and moderate-dose postoperative radiotherapy (45-50 Gy). Twenty-six patients were treated for primary disease (PD) and 19 patients for an isolated recurrence (ILR). Tumor size was >5 cm (maximum diameter) in 36 patients (80%), and high-grade histology in PD patients was present in 14 patients (54%). In nine patients, IOERT was used alone, due to previous irradiation or patient refusal. Chemotherapy (neoadjuvant and/or adjuvant) was mainly given to high-grade tumors. RESULTS: Nine patients relapsed in the extremity (20%), and 12 patients in distant sites (28%). Actuarial local control at 5 years was 88% for patients with negative/close margins and 57% for patients presenting positive margins (P=0.04). Five patients (11%) developed neuropathy associated with the treatment. Extremity preservation was achieved in 40 patients (88%). With a median follow-up of 93 months (range: 27-143 months) for the patients at risk, 25 patients remain alive (a 7-year actuarial survival rate of 75% for PD and 47% for ILR; P=0.01). CONCLUSIONS: IOERT combined with moderate doses of external beam irradiation yields high local control and extremity preservation rates in resected extremity STS. Peripheral nerves in the IOERT field are dose-limiting structures requiring a dose compromise in the IOERT component to avoid severe neurological damage.     

Soft tissue sarcoma as a second malignant neoplasm in the pediatric age group

BACKGROUND: Survivors of childhood malignancies have an increased risk of developing second malignant neoplasms (SMN) due to their prior treatment and/or genetic susceptibility. A small proportion of SMNs are soft tissue sarcomas (STS), whose prognosis is generally thought to be poor, though publications on such patients' treatment and outcome is limited. METHODS: The authors analyzed 25 patients who were registered for the Italian Cooperative Group protocols for pediatric STS from 1979 to 2000. The primary tumor was STS in five patients; Hodgkin disease in five patients; leukemia in four patients; retinoblastoma, neuroblastoma, and Wilms tumor in two patients each; and other tumor types in five patients. SMNs occurred after a median of 8 years (range, 1.9-15.0 years) and included rhabdomyosarcoma (RMS) in 4 patients, malignant peripheral nerve sheath tumor in 4 patients, extraosseous Ewing family tumor (EFT) in 4 patients, leiomyosarcoma in 3 patients, fibrosarcoma in 2 patients, synovial sarcoma in 2 patients, and other tumor types in 6 patients. Treatment generally was administered according to the guidelines for primary STS. RESULTS: Seven non-RMS patients with STS underwent surgery alone, whereas 18 patients received chemotherapy and 8 patients received radiotherapy. Retreatment was feasible with acceptable toxicity. Fifteen patients were alive in complete remission of their SMN at the time of last follow-up. Responses to chemotherapy and survival were satisfactory for patients with tumors such as RMS and EFT. Complete tumor resection was correlated with a favorable prognosis in patients with other types of STS and in patients with postirradiation sarcoma. Two patients developed a third malignancy. CONCLUSIONS: Although prior treatment may hinder the management of these patients, pediatric STS second malignancies can be cured using the same strategies used for de novo pediatric sarcomas. Long-term follow-up is mandatory given the risks of further malignancies and more severe, treatment-related side effects.     

Gemcitabine in the treatment of soft tissue sarcomas

Soft tissue sarcomas (STS) are rare mesenchymal tumors with poor prognosis once they present as advanced or metastasized disease. Only few cytostatic drugs have been proven to be active in sarcoma patients and there is a clear need for further treatment options in patients with tumors refractory to standard chemotherapy. Gemcitabine, a nucleoside analogue, has shown activity in several epithelial tumors. Clinical data on the activity of gemcitabine in STS, however, are scarce and heterogeneous. In trials including all subtypes of sarcomas response rates observed with single and multiagent schedules are ranging from 3 to 53%. Histopathological subtypes which seem to exhibit an increased susceptibility to gemcitabine are uterine leiomyosarcomas and angiosarcomas. The synergistic role of other cytostatic drugs, e.g. the role of taxanes, still remains unclear and warrants further trials. We here review the available literature on gemcitabine in the treatment of STS.     

Antiangiogenesis agents in the treatment of soft tissue sarcomas

Soft tissue sarcomas (STSs) are a heterogeneous group of malignancies that includes >50 different subtypes, each with unique clinical and pathologic qualities. In general, there is a 50% cure rate, and most cures are achieved with complete surgical resection with or without radiation therapy. The results from chemotherapeutic agents for unresectable or metastatic disease have been disappointing with minimal long‐term benefit. New targeted and novel agents are needed to improve response and survival. Tumor angiogenesis has been an intense focus in cancer therapy over the past decade. Several of numerous antiangiogenesis agents have been developed, and many already have been approved for the treatment of both solid and liquid tumors. Certain STSs are highly vascular tumors that often demonstrate angiogenesis markers. The objective of this review was to evaluate these angiogenesis markers in defining the role of angiogenesis in the treatment of patients with STS. In addition, the authors conducted an in‐depth review of the results from using key antiangiogenesis agents in the treatment of STS. Cancer 2010. © 2010 American Cancer Society.     

Soft tissue sarcoma of the upper extremity: a 5-year experience at two institutions emphasizing the role of soft tissue flap reconstruction

BACKGROUND: The objective of this study was to define the impact of soft tissue flap reconstruction on multimodality therapy for patients with soft tissue sarcomas of the upper extremity. Treatment standards continue to evolve for these patients, and, with multimodality therapy, most of them are candidates for limb-preserving surgery. Consequently, the role of soft tissue flap reconstruction is expanding. METHODS: A review was conducted of 100 consecutive patients with soft tissue sarcomas of the upper extremity who underwent surgery at several institutions between 1992 and 1997. RESULTS: Seventy-one patients underwent direct closure of defects after tumor resection, and 29 patients required soft tissue reconstruction with flaps. These groups were similar in most respects, except that 52% of the patients who required soft tissue reconstruction presented with recurrent disease (P = 0.0004), and 79% of them had tumors measuring > 5 cm in greatest dimension (P = 0.0003). The patients who required flap reconstruction had larger skin deficits after undergoing tumor resection (140 cm2) compared with the patients who had wounds that were managed by direct closure (40 cm2; P < 0.00001). Margins around the resected tumors were larger (1.62 cm) when flaps were employed compared with margins when defects were closed directly (0.87 cm; P = 0.0005). However, the number of patients with intralesional, marginal, wide, and radical resections was the same regardless of wound management. Major complications occurred in 14% of patients, but none led to death or amputation. The median follow-up was 31 months, and 66% of patients had no evidence of disease at that time. Rates of local recurrence and survival were similar for patients who underwent flap reconstruction compared with patients who underwent direct closure. CONCLUSIONS: Soft tissue flap reconstruction facilitates therapy for patients with soft tissue sarcomas of the upper extremity, so that patients with larger tumors can undergo resection, limiting complications and limb sacrifice.     

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.