Soft tissue sarcomas

Sarcomas are a heterogeneous group of rare tumors that arise predominantly from the embryonic mesoderm. They present most commonly as an asymptomatic mass originating in an extremity but can occur anywhere in the body, particularly the trunk, retroperitoneum, or the head and neck. Pretreatment radiologic imaging is critical for defining the local extent of a tumor, staging the disease, guiding biopsies, and aiding in diagnosis. Core-needle biopsy is the preferred biopsy technique for diagnosing soft tissue sarcomas. The American Joint Committee on Cancer (AJCC) staging system for soft tissue sarcomas is based on histologic grade, the tumor size and depth, and the presence of distant or nodal metastases. Despite improvements in local control rates with wide local resections and radiation therapy, metastasis and death remain a significant problem in 50% of patients who present with high-risk soft tissue sarcomas. The most common site of metastasis is the lungs, and metastasis generally occurs within two to three years after the completion of therapy. Progress in the molecular characteristics of these tumors should in the near future translate into molecularly based therapies that can be incorporated into standard treatment strategies.     

Soft tissue sarcomas of the extremity

In 1955, in a series of abstracts entitled "A Half Century of Effort to Control Cancer," Pack and Ariel wrote, "in each individual case, there is a constant battle of judgement between the wisdom of more radical amputation and the need for preservation of that important functional part." This dilemma remains with us today. In his paper on the histogenesis of tumors, Stout, relating to the philosophy of treatment, wrote that "the best chance of curing malignant tumors of the soft tissues lies in the hands of the therapist who makes the first attempt." Pack's words are as true today as they were in 1955, and although limb salvage is possible for many patients with soft tissue sarcomas, preservation of an extremity at the risk of patient survival is not a feasible option. Most efforts at less than amputative surgery must entail multimodality therapy. Although there are some reports of success with single-agent therapy, such as surgery alone, the majority of successful, nonamputative series include surgery with radiation and/or chemotherapy. It must be emphasized that an extremely important aspect of the treatment of these patients is the judgment and evaluation by the primary physician. Therefore it is extremely important that the primary physician be familiar with the many factors involved in prognosis, both in terms of local control and of systemic illness, in order for the patient to be informed of treatment options. If this is not possible, the patient should be referred to a center that is involved in active research protocols or treatments. Although rare, the soft tissue sarcomas remain among the most difficult to treat, even though over the years there has been significant progress in diagnosis, classification, and successful local control. Patient survival is based on a multitude of factors that include the histogenesis of the tumor, its grade, size, anatomical location, the surgical procedure performed, the use of preoperative or postoperative radiation, and the clinical stage of the disease--whether it is primary or metastatic. In time, it is probable that additional factors will be found.     

Soft tissue sarcomas involving the pelvis

BACKGROUND AND OBJECTIVES: Soft tissue sarcomas (STS) of the true pelvis are rare tumors and there is little information in the literature related to pelvic STS. The purposes of this review were to understand the anatomic extension of these tumors to better plan surgical treatment and to determine the outcome of these patients. METHODS: Eighteen consecutive patients presenting between 1987 and 1995 with soft tissue sarcomas involving the true pelvis were retrospectively reviewed at minimum follow-up of 18 months. Cross-sectional imaging was reviewed for each patient to determine the anatomical location of the lesions. RESULTS: The tumors were confined to the true pelvis in 4 patients, extended to the retroperitoneum in three cases, and extended to the thigh in 11 patients. Adjuvant radiation was administered to all but 2 patients who had received radiation to the region in the past and all patients underwent surgical resection (local resection in 13 patients and hindquarter amputation in 5 patients). Surgical resection had a high rate of morbidity and complications including positive resection margins in nine individuals. Of the 18 patients, 11 died at a mean time of 15.5 (2-58) months from surgery, 4 were alive with evidence of disease at a mean time of 44.3 (18-68) months, and 3 were alive with no evidence of disease at a mean time of 57 (43-71) months. CONCLUSIONS: Soft tissue sarcoma of the pelvis is fortunately a rare disease with a high risk of local and systemic disease progression despite treatment with irradiation and surgical resection.     

Soft tissue sarcomas: Preoperative versus postoperative radiotherapy

External beam radiation may be given either before or after excision of a primary soft tissue sarcoma. This study was undertaken to determine whether or not the timing of radiotherapy was associated with any difference in either local control, survival, or incidence of complications. The files of 112 patients with a primary, nonmetastatic, extremity soft tissue sarcoma, treated with limb salvage surgery and irradiation were evaluated. Data regarding tumor stage, grade, site, surgical margin, dosage and timing of radiotherapy, treatment complications, disease relapse, and relapse-free survival (RFS) were analyzed. Kaplan-Meier lifetable analysis was used to determine survival estimates. There was no significant difference in the 5-year RFS between patients receiving radiotherapy (RT) preoperatively versus postoperatively; 56 ± 15% and 67 ± 12% (P = 0.12, Mantel-Cox), respectively. There was no significant difference in the overall survival between patients receiving RT preoperatively versus postoperatively; 75 ± 15% and 79 ± 11% (P = 0.94), respectively. Actuarial local control at 5 years for preoperative versus postoperative RT patients was not statistically different; 83 ± 12% versus 91 ± 8% (P = 0.41), respectively. Wound complications were more frequent in preoperative RT patients (31%) compared to postoperative RT patients (8%) (P = 0.0014, chi-square). Preoperative irradiation was not associated with any benefit in terms of relapse-free survival, overall survival or actuarial local control in this series. A higher incidence of major wound complications was found among patients treated with preoperative irradiation. We recommend that patients with a resectable extremity soft tissue sarcoma be treated with postoperative irradiation, reserving preoperative irradiation for those situations in which either the tumor is initially thought to be unresectable or the original tumor boundaries are obscured. © 1996 Wiley-Liss, Inc.     

Soft tissue sarcomas of the lower extremity: surgical treatment and outcome.

AIMS: The aims of this retrospective follow-up study were to evaluate the justification for limb-saving multi-disciplinary treatment of soft tissue sarcomas (STS) and to report the results achieved by our treatment protocol. Local control was studied, with emphasis on tumour depth, operation margin and need for post-operative radiotherapy. METHODS: We examined 130 patients with STS in the lower limb referred to the multi-disciplinary group of Helsinki University Central Hospital. For the survival analysis 106 patients with local disease remained. The goal of treatment was to preserve a functional limb. Wide excision was attempted. If the margin was less than 2.5 cm, post-operative radiotherapy (RT) was delivered to all except 20 patients. RESULTS: Ninety-two per cent of the patients were treated by limb salvage. The success rate of free flaps was 16 out of 18. The 5-year disease-specific overall survival was 76%, metastasis-free survival 72% and local control 79%. Prognostic factors for local recurrence were extracompartmental site and large size; for development of metastases high grade, extracompartmental site and large size; for decreased disease-specific overall survival high grade, large size and advanced age. Local control of intramuscular tumours (n=6) was 100%, subcutaneous tumours (n=38) 94% and tumours penetrating the deep or muscle fascia and those locating extracompartmentally (n=62) 67%. CONCLUSIONS: Limb salvage in patients with STS is possible with an acceptable outcome by selective combination of treatment modalities. Modern plastic surgical methods with free tissue transfers are successful and often needed. Subcutaneous and intramuscular tumours have good local control. The outcome is poorest for tumours penetrating the deep or muscle fascia and for those located extracompartmentally, and patients with such tumours might be a target for adjuvant therapy. Treatment should be coordinated by multidisciplinary teams.     

Soft tissue sarcomas of the popliteal fossa: outcome and risk factors.

BACKGROUND: Limb salvage surgery of popliteal soft tissue sarcomas may be hampered due to the incomplete anatomical containment of this region and the vicinity of neurovascular structures. The scope of this study was to determine outcome and to define risk factors. PATIENTS AND METHODS: 27 patients (53.3+/-15.8 y; 16/27 male) with popliteal soft tissue sarcomas were assessed. Mean follow-up was 40.9+/-33.8 months (48.5+/-36.7 months in surviving patients). 9/27 patients were included after prior treatment elsewhere (5 after intralesional resections and 4 local recurrences). The lesions were staged IB in 8/27 patients, IIB in 17/27 and III in 2/27. Immediate amputations were performed in 7/27 patients. 15/27 patients were subjected to radiation therapy (preoperative in 6/15 cases), 8/27 patients received chemotherapy (5/8 preoperatively). RESULTS: Overall survival and disease-free survival at 5 y was 63.0% and 59.5%. Local recurrence occurred in 2 patients. 8/27 patients developed metastatic disease after 28.9+/-9.8 months. Survival (p=0.397) and disease-free survival (p=0.113) did not differ in patients after amputations vs limb salvage. Application of radiation therapy was associated with a better survival (p=0.003). Complications related to the surgical intervention were recorded in 2/27 patients, complications related to radiation therapy occurred in 6/15 patients. DISCUSSION: Despite being extra-compartmental, popliteal sarcomas can be treated with a high rate of limb salvage while equal safety compared to amputations is maintained. Irradiation improved survival in our patient population. In cases with involvement of neurovascular structures, preoperative down-staging with radio or chemo-therapy may prevent amputation.     

Soft tissue sarcomas of the adult thoracic wall

Forty-nine adult patients with soft tissue sarcomas of the thoracic wall have been treated by the Division of Surgical Oncology at the University of Illinois. Fibrosarcoma was the most common histologic type (20%). Patients with dermatofibrosarcoma protuberans had the longest mean overall survival time (150.8 months). The mean overall survival time for all patients was 98.2 months, and the disease-free 2-, 5-, and 10-year survival rates were 68%, 51%, and 34%, respectively. Wide excision was the treatment of choice; selected patients also received adjuvant radiotherapy, chemotherapy, or both. In all 10-year survivors, the sarcomas were low grade and well differentiated, or were less than or equal to 5.0 cm in diameter. Aggressive treatment afforded these patients good long-term results.     

Soft tissue sarcomas of the hand and foot

A retrospective study was made of 82 soft tissue sarcomas of the hand and foot. Prognosis was related to histopathologic grade of malignancy and success or failure of local tumor control. After treatment with curative intent, low-grade tumors gave a 5-year survival rate of 90%, compared to 63% for high-grade tumors. Simple excision or limited amputation of the digit, hand, or foot yielded a 5-year survival rate of 68% (15/22) and a local recurrence rate of 32%. Amputation below the elbow or knee or higher resulted in a similar survival of 68% (19/28) but no local recurrences. All patients who developed local recurrences died, except for two with low-grade tumors and one patient lost to follow-up. These observations indicate the need for systemic chemotherapy to prevent death from metastasis, and for effective local tumor control. Conventional radiation therapy may be difficult to apply at these sites. Innovative local treatment approaches to preserve limb function without jeopardizing tumor control merit study.     

Soft tissue sarcoma in adults.

Soft tissue sarcomas are a heterogeneous group of tumors, consisting of numerous histiotypes that all share a putative common mesenchymal origin. Although prognosis of these tumors is determined by clinical parameters (size, location, and resection margin status) and pathologic features (mitotic activity and necrosis), the histologic subtype has never been shown to be a consistent independent prognostic factor. Some relevant differences among these histiotypes are emerging, in specific biological parameters such as proliferation indices, in integrin expression profiles, and with regard to drug sensitivity. Several biological factors are considered to be prognostically important. Most attention is directed to regulators of cell-cycle progression. The significance of p53 dysregulation is confirmed by the inhibition of cellular proliferation, both in in-vitro and in in-vivo sarcoma models, after reintroduction of wild type p53. A multidisciplinary approach is essential for the optimal treatment of soft tissue sarcomas. Multimodality treatment has led to a patient-tailored approach with limb-sparing resections integrated with external and/or interstitial irradiation. The value of chemotherapy both in the neoadjuvant and the adjuvant setting, although of critical value in other sarcomas such as Ewing's sarcoma and osteosarcoma, remains to be established for soft tissue sarcomas.     

Soft tissue sarcomas: update on molecular data]

Soft tissue sarcomas are rare and may be a source of problems for diagnosis and treatment. Four types of genetic disorders can be distinguished: translocations, gene amplifications, mutations and complex genetic imbalances. Detection of these disorders may help in diagnosis and in determining prognosis. Detection of specific translocation is recommended in synovial sarcoma, alveolar rhabdomyosarcoma or PNET diagnosis because of therapeutic consequences; in case of rarer histologic type (low grade fibromyxoid sarcoma, clear cell sarcoma, infantile fibrosarcoma...), it may confirm the diagnosis. In some cases, some translocations have a prognostic value (alveolar rhabdomyosarcoma) whereas it is discussed in others (synovial sarcoma). The techniques used to detect these translocations are very sensitive so it may be used to detect microscopical metastasis (bone marrow metastasis of alveolar rhabdomyosarcoma for example). Detection of MDM2 and CDK4 genes amplifications (FISH or quantitative PCR) may be sometimes useful in well differentiated and dedifferentiated liposarcomas diagnosis. Mutation detection of KIT or PDGFRA may help in GIST diagnosis and type of mutation is predictive of response to treatment. Study of complex genomic imbalances in sarcomas is not used in routine practice but remains useful in research.     

Soft tissue sarcomas in skin: presentations and management

Soft tissue sarcomas are a rare but heterogeneous family of malignant tumors that are predominantly found deep to the integumentary layer. Only a small number of these primary mesenchymal tumors actually originate from the dermal layers. A systematic approach to the evaluation and workup of these neoplasms can prevent inappropriate management. After staging evaluation, most of these tumors are primarily managed with en-bloc surgical resection. Other adjuvant therapies routinely employed include chemotherapy and radiation therapy. Proper treatment typically involves participation of a multidisciplinary care team for optimal outcome. General principles and treatment strategies will be discussed along with a review of the more common cutaneous manifestations of sarcoma.     

Soft tissue sarcomas in infancy and childhood

Thirty-one soft tissue sarcomas in children were studied. The majority of these tumors occurred between the ages of 6 and 10; there were 18 boys and 13 girls. Three main histologic types were encountered, 14 children had fibrosarcoma, 13 rhabdomyosarcoma, 2 had solitary malignant schwannoma, and in 2 the histogenetic origin could not be determined. Head and neck region was found to be the most common anatomical site, and 16 of 31 patients had their primary tumors in this region. In the rhabdomyosarcoma group of the 11 eligible patients, 6 lived free of disease for 5 years; in the fibrosarcoma group of the 12 eligible patients, 6 lived for 5 years or more. Both children with solitary malignant schwannoma are living. It is proposed that rhabdomyosarcoma in children be treated by combining irradiation, chemotherapy, and surgery while fibrosarcoma should be treated by excision alone. Furthermore, it is also proposed that, when the histogenetic type of a tumor can not be determined, these children be treated as having rhabdomyosarcoma.     

Soft tissue sarcomas of the adult head and neck

From 1969 to 1983, 53 adult patients with head and neck soft tissue sarcomas were evaluated and treated by the Division of Surgical Oncology at the University of Illinois. The most common anatomic location was the neck (36%), and these patients had the highest 5-year disease-free survival rate (67%). Fibrosarcoma was the most common histologic type (26%); patients with aggressive fibromatosis had the longest mean survival time (93 months). The mean overall survival time was 58.7 months, and the disease-free 2-year, 5-year, and 10-year survival rates were 68%, 54%, and 28%, respectively. Wide excision was the treatment of choice, with adjuvant radiotherapy or chemotherapy, or both, used in selected patients. In all of the long-term survivors, the tumors were either well-differentiated or less than or equal to 5.0 cm in diameter. It is apparent that aggressive therapy of such tumors can provide good long-term results.     

Soft tissue sarcomas in the first year of life

BackgroundSoft tissue sarcomas (STS) occurring in the first year of life represent a rare entity. Challenges in delivering optimal therapy may affect the outcome in this very young population.MethodsWe searched the SEER database for records of infants less than 1 year of age, with a reported diagnosis of STS who were diagnosed from 1973 to 2006. We analysed their clinical features and survival. These patients were also compared to older patients (1–18 years old) in order to understand the differences between the two groups.ResultsThe incidence rate of STS in the first year of life was 16.0 per million. As an entity, they represented 7.3% of malignancies reported in the first year of life. One fifth of these tumours (20.9%) were reported to be metastatic at diagnosis. The most common histologies were rhabdomyosarcoma (n = 99, 32.8%), fibrosarcoma (n = 74, 24.5%), malignant rhabdoid tumours (n = 43, 14.2%) and haemangiopericytoma (n = 12, 4.0%); except for rhabdomyosarcoma, the other 3 entities were very rare in older children. The 5-year survival of STS in children less than 1 year of age (62 ± 3.0%) was significantly worse than that of older children (71 ± 0.9%, P = 0.0002). In a multivariate model, histologic types other than fibrosarcoma and haemangiopericytoma (HR, 5.7; 95% CI, 2.28–14.20) as well as advanced stage (HR, 5.15; 95% CI, 3.28–8.10) were found to be significant adverse prognostic factors. Significantly less use of radiation was reported in infants when compared to older children (P < 0.0001).ConclusionAs a group, infantile STS are associated with worse survival than STS in older children. Outcome, however, is significantly associated with histologic subtype, with infantile fibrosarcoma and infantile haemangiopericytoma having better outcomes. Avoidance of radiotherapy in this young age may contribute to worse outcomes.