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PubMed1991

Adjuvant therapy for adult patients with soft tissue sarcomas.

Soft tissue sarcomas are relatively uncommon malignant tumors in the adult population. These malignant tumors arise largely from the connective and supportive tissues in various anatomic sites. Adjuvant radiation therapy can be combined with conservative, non-amputative surgical procedures to achieve a high frequency of tumor control in most primary sites. In spite of local tumor control, a high proportion of patients will subsequently die from distant metastases. Randomized trials of adjuvant chemotherapy for such adult sarcomas are inconclusive. They suggest a possible benefit for patients with high-grade lesions of the extremities. Several trials indicate a possible local control advantage. However, because of potential morbidity of adjuvant chemotherapy, its use at this time should be restricted to clinical trials.

Adult↗

PubMed1996

Soft tissue sarcomas.

Soft tissue sarcomas are relatively rare tumors with an annual incidence of 5000 to 6000 in the United States. The primary therapy is surgical resection with an adequate margin of normal tissue. For patients at high risk local control is improved with postoperative adjuvant radiation. Local recurrence rates vary depending on the anatomic site. In extremity lesions one third of patients will have locally recurrent disease with a median disease-free interval of 18 months. Treatment results for extremity local recurrence may approach those for primary disease. Isolated pulmonary metastases may be resected with 20% to 30% 3-year survival rates. Patients with sarcomas in other sites present similar but more difficult problems in terms of local control and management of disseminated disease. Patients with unresectable pulmonary metastases or extrapulmonary metastatic sarcoma have a uniformly poor prognosis and are best treated with systemic chemotherapy.

Female↗

PubMed1991

Current diagnosis and therapy of soft tissue sarcomas.

Soft tissue sarcomas are a difficult group of cancers to treat and require a multimodality approach. The ideal surgical procedure should obtain adequate resection margins and also attempt to spare limb function. Radiation therapy has a prominent role in preventing local recurrence of the tumor postoperatively. Other methods of delivering radiation therapy are currently being explored to achieve maximum benefit and minimize treatment complications. The role of postoperative adjuvant chemotherapy has yet to be defined, and ongoing clinical trials are in progress. As further advances in clinical and investigational sciences are uncovered, it is hoped that ultimately the best combination of treatments for this tumor will be found.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

The multidisciplinary approach to treatment of soft tissue sarcomas.

Soft tissue sarcomas are rare tumors including many histological subtypes. They are pre-eminently tumors for which the multidisciplinary approach to treatment is of utmost importance. The two most frequently applied staging systems both require experienced assessment of radiology and pathology, and stage is a prominent prognostic factor for survival that guides the choice of treatment modalities. For primary treatment radical surgery is still the backbone. In many instances postoperative radiotherapy is a valuable and often necessary complementary treatment. The role of preoperative radiotherapy and/or chemotherapy needs to be defined although preliminary results are interesting. Chemotherapy as an adjunct to surgery should still be considered investigational. In metastatic disease "standard" chemotherapy has a definitive though moderate activity, but recent data on dose-intensified chemotherapy suggest that results may be further improved.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Primary multidisciplinary management of extremity soft tissue sarcomas.

Soft tissue sarcomas (STS) are a rare and heterogeneous group of malignancies that most commonly present as large painless masses deep in the muscular compartments of the extremities. Investigation and treatment of these patients must be undertaken at a tertiary referral unit. Staging studies must include a high-quality magnetic resonance imaging (MRI) scan of the local site and a computed tomography (CT) scan of the chest to investigate for possible metastatic disease. Review of biopsy material must be undertaken by an experienced musculoskeletal pathologist. Currently, histologic diagnosis and grade are assigned to the tumor, but in tumors such as synovial sarcoma and Ewing's family of tumors, molecular evaluation is becoming crucial for diagnostic, prognostic, and therapeutic reasons. Surgical resection of sarcomas with negative surgical margins remains the mainstay of treatment. Surgical treatment alone is indicated for small superficial masses that are not adjacent to bone or neurovascular structures. However, in large deep masses where surgical margins are likely to be close in order to preserve important neurovascular structures and bone, combined treatment using surgical resection and radiation results in acceptable local control rates and reasonable patient function. It is incumbent on the management team to decide on timing of radiotherapy as a practice. This decision is based on several factors but potential complications must be taken into account. In this regard the long-term effects on normal tissues must be considered. Functional outcome has become an essential consideration when recommending treatment. If promising techniques become available to reduce the incidence of wound complications or to decrease the dose of radiation to normal tissue, preoperative radiation should be considered in light of its lower incidence of long-term effects that result in reduction in patient function.

Drug Therapy↗

PubMed1981

Radiation therapy for soft tissue sarcoma.

Soft tissue sarcomas can be adequately treated with wide local excision and postoperative irradiation, rather than the amputation of the affected extremity. Local control and good function can be achieved in the great majority of patients treated with radiation therapy, with particularly good results (95% local control) obtained for lesions of the distal extremity i.e., below the elbow or knee. The most common site of failure is distant metastasis, and the outstanding prognostic indicator is histologic grade. Disease-free survival correlates strongly with grade, with 85%, 51%, and 17% 2-yr disease-free survival for grades 1, 2, and 3, respectively. Lymph node metastasis is an uncommon first site of failure, and prophylactic nodal irradiation or lymphadenectomy is not recommended. The value of chemotherapy or immunotherapy is not firmly established as far as enhancing local control. It is hoped that distant metastasis can be prevented by the use of such adjuvant therapy. Locally advanced, nonresectable sarcoma may be better treated with high linear energy transfer (LET) radiation, and promising results have been reported with fast neutron treatment.

Breast Neoplasms↗

PubMed2006

[Three cases of retroperitoneal soft tissue sarcoma].

Soft tissue sarcomas (STS) are rare tumors that comprise only 1% of all malignancies. The retroperitoneum is an uncommon site of origin for them, accounting for about 10% of all STS. In case 1, a 30-year-old man complaining of chest pain was found to have a retroperitoneal tumor around the left kidney by computed tomography (CT). The tumor was removed along with the left kidney. Histologically, it was fibrosarcoma 3,000 g in weight. In case 2, a 31-year-old woman complaining of abdominal distension was found to have a retroperitoneal tumor by CT. The tumor was removed in the same way. It was undifferentiated sarcoma 2,000 g in weight. In case 3, a 73-year-old woman, who had no complaint was found to have mass in the left lateral region during follow up for cardiac failure. She was referred to our department for treatment of retroperitoneal tumor revealed by ultrasound and CT. The tumor was dedifferentiated liposarcoma 2,420 g in weight. All three patients had local recurrences, and two of them underwent a second surgical procedure.

Adult↗

PubMed1999

The local management of soft tissue sarcoma.

Soft tissue sarcomas (STS) are rare tumors arising from the connective tissues. STS can arise at any anatomic site, can demonstrate varied behavior and prognosis, and therefore present a formidable challenge in management. The local treatment of STS demands technical complexity in the application of diagnostic tools, including pathology and imaging, as well as treatment approaches, including surgical ablation and reconstruction, radiotherapy, and, in defined cases, chemotherapy. The understanding of the management of these lesions is profoundly dependent on the multidisciplinary setting, where experience has been gained and skills are available to increase the likelihood of a successful result. Several proven options are available for optimal local management, and the choice of approach depends on the prevailing practice and resource profile of the treating center. With modern approaches, the local control rate can be expected to be at least 90% for extremity lesions, which constitute the most common STS. The experience in other anatomic sites is less favorable as a result of a combination of late diagnosis, technically difficult access sites, and possibly less familiarity with these less common presentations. The disappointing results make it all the more important for patients to be referred to a multidisciplinary setting with experience in sarcoma management to maximize the chance of successful local outcome.

Amputation, Surgical↗

PubMed1995

Preoperative therapy for soft tissue sarcoma.

Soft tissue sarcomas appear to be an ideal tumor type for delivering preoperative therapy. The rationale for preoperative therapy is that it is delivered to undisturbed tissue planes with well-oxygenated tissue. This is of great benefit for radiation therapy, because with new computed tomography scan treatment planning it is possible to completely delineate the tumor without surgical clips or postoperative hematoma (or both) obscuring the tumor margin.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

[Radiotherapy of soft tissue sarcomas].

Soft tissue sarcomas are uncommon neoplasms that represent approximately 1% of all malignancies. It is clear that sarcomas require a therapeutic approach that establishes local control and thereby eliminates the potential of metastasis for patients with truly limited disease. Localized sarcomas are generally treated by surgery. Excision must be complete, with a wide margin of normal tissue, and along anatomic planes, or recurrence will almost certainly follow. Amputations are still occasionally required, although limb salvage procedures are being used increasingly, particularly in the context of multimodality therapy with irradiation or chemotherapy. Radiotherapy can be highly effective for improving local control and is used as adjuvant therapy, either preoperatively or postoperatively. In case of non-in-sano-resection a salvage surgery is indicated. Use of adjuvant postoperative radiotherapy allows for more conservative surgery without compromising local control, and therefore often may allow limb salvage where amputation might otherwise be necessary, e.g. in case of R1- or R2-resection without a new resection, a close margin or large tumors with histologic G2 or G3 grading and in case of local relapses. Local control rate of 90% are reported for the combination of pre- and postoperative radiotherapy. Prognosis is still limited by distant metastases. In case of unresectable tumors neutron radiotherapy results in 50% local control. New approaches e.g. hyperfractionated-accelerated radiotherapy, interoperative radiotherapy and chemoradiotherapy are promising perspectives, which are being evaluated in clinical studies. Desmoid tumors benefit of postoperative radiotherapy in case of R1-resection or relapse.

Combined Modality Therapy↗

PubMed1986

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.

Adolescent↗

PubMed2004

Human DNA damage checkpoints and their relevance to soft tissue sarcoma.

Soft tissue sarcoma (STS) is a malignant neoplasm, arising in mesenchymal tissues, that is difficult to treat clinically because it can be highly resistant to chemo-radiotherapy. At present, the mechanism of that resistance remains unclear. Cell cycle checkpoints engender strict control of cell proliferation, arresting the cell cycle to provide time for repair or apoptosis when DNA damage is induced by unprogrammed extrinsic events. These pathways involve at least two checkpoints: one at the G1/S transition and one at the G2/M transition. The p53 gene, which is mutated in several malignant tumors, plays an important role in DNA repair at the G1/S transition; however, there is little information on the G2/M checkpoint in STS. In the present study, several proteins (phospho-p53, -cdc25, -cdc2, -Chk1 and -Chk2) involved in checkpoint pathways were investigated using immunohistochemistry in STS specimens. Most STSs maintain a well-preserved G2/M checkpoint despite the loss of the G1/S checkpoint (phospho-p53: 4.9% (2/41); -cdc25: 41% (17/41); -cdc2: 61% (25/41); -Chk1: 29% (12/41); -Chk2: 46% (19/41)). Furthermore, in a postoperative chemotherapy case the number of cells positive for phospho-cdc25 and -Chk2 was higher in a recurrent tumor than in the primary tumor (n = 7, P = 0.046 < 0.05, Wilcoxon signed-ranks test). These findings indicate that the G2/M checkpoint pathway is well preserved and might contribute to the chemotherapeutic resistance associated with STS.

Adolescent↗

PubMed2006

The role of genetic testing in soft tissue sarcoma.

Soft tissue tumours represent a heterogeneous group of mesenchymal lesions and their classification continues to evolve as a result of incorporating advances in cytogenetic and molecular techniques. In the last decade traditional diagnostic approaches were supplemented with a significant number of reliable molecular diagnostic tools, detecting tumour type-specific genetic alterations. In addition, the successful application of some of these techniques to formalin-fixed paraffin-embedded tissue made it possible to subject a broader range of clinical material to molecular analysis. Thus, molecular genetics has already become an integral part of the work-up in some tumours, such as paediatric small blue round cell tumours, which demonstrate characteristic translocations. Several lines of evidence suggest that sarcomas can be divided into two major genetic groups: (i) sarcomas with specific genetic alterations and usually simple karyotypes, such as reciprocal chromosomal translocations (e.g. FUS-DDIT3 in myxoid liposarcoma) and specific oncogenic mutations (e.g. KIT mutation in gastrointestinal stromal tumours); and (i) sarcomas with non-specific genetic alterations and complex unbalanced karyotypes. Some of these genetic abnormalities, including chromosomal numerical changes, translocations, gene amplifications or large deletions can be apparent at the cytogenetic level (karyotyping, fluorescence in situ hybridization), while others, such as small deletions, insertions or point mutations, require molecular genetic techniques (polymerase chain reaction and sequence analysis). This review focuses on the applicability of genetic testing in the diagnosis and prognosis of soft tissue sarcomas, and gives a realistic appraisal of the ancillary role of molecular techniques, including its advantages and limitations.

Base Sequence↗

PubMed1999

Positron Emission Tomography in Grading Soft Tissue Sarcomas.

Soft tissue sarcomas present with varied radiological appearances. Positron imaging with [F-18] fluorodeoxyglucose (FDG PET) has recently made promising contributions to management of patients by providing a noninvasive means for evaluating tumor metabolism and providing important biological information about soft tissue malignant tumors. PET imaging not only gives quantitative data on metabolic rates of tumors but can also readily provide semiquantitative data of uptake of tumors by measuring uptake ratios. These values have been helpful for noninvasively grading tumors. This value is called the tumor standard uptake value (SUV). The tumor grades (low, intermediate, high) mean SUV values show a high level of significance in discrimination among tumor grade groups.

Journal Article↗

PubMed2005

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.

Animals↗

PubMed2004

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.

Adult↗

PubMed1998

[Frequency, distribution and prognostic relevance of p53 mutations in soft tissue sarcomas].

Soft tissue sarcomas although rarely occurring (about 1% of malignant tumors), are because of their histo-morphological diversity and often similar appearance to tumor-like lesions difficult to characterize and estimate in their tumor biological behaviour. Analysis of molecular characteristics as alterations in tumor-suppressor and oncogenes may allow insight in STS genesis. We have chosen the in carcinomas well, but in STS not comprehensively investigated tumor-suppressor gene p53 for mutational analysis. In 16 out of 146 STS patients we could identify p53-mutations. In a multivariate Cox-regression analysis prognosis was correlated with the p53-mutation type. However, only patients with non-frameshift mutations possessed a poorer prognosis (RR = 2.42; p = 0.014) in comparison to patients without mutations, but frameshift-mutations didn't seem to affect prognosis negatively. Compiling our results and those of the literature an overall frequency of 16.3% of p53-mutations in STS, with various frequencies in different entities is detectable. STS specific hotspots are not recognizable. Rather mutational hotspots in codons 175, 245, 248 and 273 well known from studies in carcinomas are also apparent in STS. Summarizing, we want to state that the occurrence of p53-mutations (non-frameshift mutations) is of prognostic importance in STS. Combination of histo-pathological, clinical and molecular characteristics may allow to distinguish in future different groups of patients for an individual treatment.

Codon↗

PubMed1997

The epidemiology of soft tissue sarcoma.

Soft tissue sarcoma (STS) accounts for approximately 1% of all cancers diagnosed annually in the United States. Population-based data from Connecticut covering the years 1935-1989 have shown an increasing incidence of STS in both genders, with a greater increase among men than women. The recent increase in acquired immune deficiency syndrome-related Kaposi's sarcoma does not explain the upward trend in STS, dating back decades. Etiologic heterogeneity is suggested by epidemiologic variations that have been observed by subsite and cell type. Among the environmental factors associated with STS are external radiation therapy, Thorotrast, arsenical pesticides and medications, phenoxyherbicides, dioxin, vinyl chloride, immunosuppressive drugs, alkylating agents, androgen-anabolic steroids, human immunodeficiency virus, and human herpes virus type 8. In addition, STS occurs excessively among persons with certain heritable states including retinoblastoma, Li-Fraumeni syndrome, Gardner's syndrome, Werner's syndrome, nevoid basal cell carcinoma syndrome, neurofibromatosis type 1, and some immunodeficiency syndromes. These risk factors account for a minority of STS cases but provide leads for further epidemiologic and interdisciplinary studies into the genetic and environmental determinants of various forms of STS.

Environmental Exposure↗