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PubMedDate not supplied

Biological prognostic factors in adult soft tissue sarcomas.

Adult soft tissue sarcomas (STSs) are a rare group of highly heterogeneous neoplasms arising in different tissues. They are locally aggressive and can produce recurrence and distant metastasis. The most common metastatic sites are lung, lymph nodes, liver, bone and soft tissues. Staging for STSs has been based on some prognostic information: grade (low vs. intermediate/high grade), size (small vs. large tumors), depth of infiltration (superficial vs. deep neoplasms) and presence or not of distant metastasis. In the last 10 years, a plethora of new markers (proliferation markers and DNA alteration, P-gp, p53, TLS-CHOP, cyclins, survivin, TERT, PAX3-PAX7/FKHR, SYT-SSX1/2, VEGF, E-cadherin and beta-catenin, nm23, SKP-2, p27, CD40) has been studied with regard to their role in promoting progression (in a laboratory setting) and then determining prognosis and therapy (in a clinical setting). In the present survey, we focused on the role of new biological prognostic factors in STSs and also reported the quality of such studies with an ad hoc designed questionnaire.

Adult↗

PubMed2005

Prognostic significance of augmented metallothionein (MT) expression correlated with Ki-67 antigen expression in selected soft tissue sarcomas.

In soft tissue sarcomas, the most important prognostic criteria include extent of malignancy (G), size of the tumour and intensity of Ki-67 antigen expression. In recent times expression of metallothionein (MT) in cells of some malignant processes of epithelial origin was found to correlate with intensity of Ki-67 antigen expression and to carry a possible prognostic significance. The present study aimed at a demonstration of prognostic value of MT expression and at comparing it with Ki-67 antigen expression and G grade in selected soft tissue sarcomas. Immunohistochemical studies were performed on paraffin sections in 54 cases of malignant fibrous histiocytoma (MFH), 18 cases of liposarcoma and 20 cases of synovial sarcoma. The extent of MT and Ki-67 antigen expression was evaluated and an attempt was made to correlate the results with each other and with grade of the tumour. Expression of MT was evident both in the cytoplasm and in cell nuclei of all studied sarcomas. The most pronounced MT expression was noted in MFH-type tumours. The extent of Ki-67 antigen expression was similar in MFH and liposarcoma and was the lowest in synovial sarcoma. In MFH, liposarcoma and synovial sarcoma a pronounced positive correlation was documented between expression of MT and Ki-67 antigen (r=0.85; p<0.001; r=0.93, p<0.0001; r=0.79, p<0.0001). In all types of the tumours a positive relation was detected between MT expression, expression of Ki-67 and G grade of malignancy in the tumour. Moreover, patients with higher MT expression in the studied tumours demonstrated a shorter survival. MT expression in soft tissue tumours of MFH, liposarcoma and synovial sarcoma type strongly correlated with intensity of proliferation (Ki-67) and G grade and could be useful in defining the extent of malignancy and in prognostic appraisal in the tumours.

Humans↗

PubMed1994

Imaging of soft-tissue sarcomas.

Soft-tissue sarcomas are encountered only infrequently, but their diagnosis is important because the long-term prognosis is usually good if the tumour is properly managed. The role of various imaging modalities in the evaluation of these neoplasms is discussed, with special emphasis on magnetic resonance imaging. The authors review the importance of imaging in tumour detection, characterization, staging and surveillance after therapy, and they emphasize the critical subject of proper biopsy technique.

Humans↗

PubMed1999

Current aspects of the pathology of soft tissue sarcomas.

In soft tissue sarcomas, advances in pathological techniques, including immunohistochemistry, cytogenetics, and molecular genetics, have improved diagnostic accuracy, confirmed or clarified interrelationships between tumor subtypes, and revealed mechanisms of tumorigenesis. Many sarcomas are associated with abnormalities of tumor-suppressor genes, and several types have been found to have specific chromosomal translocations. These data and correlative clinicopathologic studies, although confirming many traditional pathological views, enable refinement or reassessment of terminology and classification of some small round cell, spindle cell, pleomorphic, and lipogenic tumors. New factors are emerging for prediction of tumor behavior, which might ultimately relate to therapy once a wider range of treatment options becomes available. This article reviews these current aspects of sarcoma pathology.

Cell Transformation, Neoplastic↗

PubMed1989

Management of extremity soft-tissue sarcoma.

Soft-tissue sarcomas remain relatively uncommon neoplasms, but they present major problems for both the patient and clinician. The identification of prognostic variables based on both clinical and histologic factors has allowed comparisons to be made between various therapeutic regimens. In extremity sarcoma, a more conservative operation utilizing adjuvant radiotherapy has decreased the need for radical surgery and maximized function without loss of survival benefit. The identification of high-risk groups, that is, patients with high-grade, large lesions, has highlighted the inadequacies of treatment in some areas. Similarly, this has led to more aggressive and innovative developmental programs. The progress, understanding, and therapeutic management of extremity lesions have not been matched in visceral and retroperitoneal tumors. Current efforts are directed at more appropriate use of radical surgery, maximizing conservative function-sparing operations with the use of adjuvant local therapy, and development of new regimens directed at prevention and treatment of metastatic disease.

Humans↗

PubMed1997

Soft tissue sarcomas.

The soft tissue sarcomas (STS) constitute approximately 15% of all canine and 7% of all feline skin and subcutaneous tumors. STS are tumors that arise from a variety of mesenchymal tissues. The aggressive nature of STS in cats, especially those tumors occurring after vaccination, suggests that novel therapies should be investigated.

Animals↗

PubMed1986

Adult head and neck soft-tissue sarcomas.

Adult soft tissue sarcomas of the head and neck are so rare that an accurate diagnosis and appropriate therapy are frequently delayed. A retrospective study of such patients seen at the University of Illinois over the last 15 years has helped to better characterize this disease entity. Patients with sarcoma of the neck, the most common anatomic location (37 per cent), had the highest 5-year disease-free survival rate (67 per cent). Fibrosarcoma was the most common histologic type (25 per cent). Aggressive fibromatosis patients experienced the longest mean survival time (93 months). The disease-free 2-year, 5-year, and 10-year survival rates were found to be 68, 54, and 28 per cent, respectively. Wide excision was the treatment of choice, with adjuvant radiotherapy or chemotherapy, or both, used in selected patients. The sarcomas of all long-term survivors were either well-differentiated or 5.0 cm or less in diameter. It is evident that aggressive therapy of adult head and neck sarcomas can provide good long-term results.

Adult↗

PubMedDate not supplied

Low dose adriamycin and ifosfamide in the treatment of advanced adult soft tissue sarcomas.

BACKGROUND: Soft tissue sarcomas are infrequent tumors (up to 1% of all neoplasms) in adult patients. Treatment of advanced disease is largely unsatisfactory. Only a few drugs are active agents and combination regimens offer limited and short-lived activity. High dose chemotherapy may be administered only to limited groups of patients. PATIENTS AND METHODS: We evaluated, in a phase II study, the adriamycin and ifosfamide combination regimen. The drugs were administered at 60 mg/sqm and 6 g/sqm dosage, respectively. The total number of treated patients was 42 of which 40 were evaluable. RESULTS: We observed 6 complete responses (14% response rate) and 6 partial responses (14%). The mean survival was 6 months (median 7.6 months). Toxicity was limited and reversible. CONCLUSION: While high dose chemotherapy may be reserved for selected groups of patients, an adriamycin and ifosfamide combination regimen at conventional doses can be administered to the great majority of patients with suboptimal performance status or with advanced age.

Adolescent↗

PubMed2000

Menstrual and reproductive factors and risk of soft tissue sarcomas.

BACKGROUND: Soft tissue sarcomas (STS) are a heterogeneous group of neoplasms whose etiology remains largely undefined. A role for female hormones in the development of STS has been suggested. To investigate this possibility, the authors analyzed data from a hospital-based case-control study conducted in Northern Italy between 1983 and 1998. METHODS: Cases were 104 women aged < 79 years with incident STS who were admitted to the cancer institutes and major teaching and general hospitals. Controls were 505 women admitted to the same network of hospitals for acute, nonneoplastic, nongynecologic, and nonimmune-related conditions. RESULTS: The multivariate odds ratio (OR) for women aged >/= 15 years compared with those aged < 12 years at menarche was 1.94 (95% confidence intervals [95% CI], 0.80-4.74). No association with STS risk was observed for menstrual cycle pattern, age at menopause, parity, and abortions. Late age at first pregnancy and birth were found to be related to an increased risk of STS, with an OR of 3.16 (95% CI, 0. 96-10.44) and 2.79 (95%% CI, 0.79-9.90) for women aged >/= 30 years at first pregnancy and birth compared with those aged < 20 years. The trend in risk was significant for age at first pregnancy. No relation with the risk of STS emerged for age at last birth and time since first or last birth. CONCLUSIONS: The risk of STS was found to be weakly related to late age at first pregnancy or birth, but not to other menstrual and reproductive factors.

Abortion, Induced↗

PubMed2003

The follow-up of adult soft-tissue sarcomas.

Soft-tissue sarcomas are a rare and heterogeneous group of diseases with variable biology and pattern of metastases. These characteristics make it challenging to conduct large, randomized studies that could be used to generate evidence-based guidelines for unique subsets. Much of the data summarized here therefore represents standard practice based on the consensus of a group of experienced specialists and retrospective analysis of large databases. A surveillance guideline should be based on known prognostic factors, outcomes in individual subsets, and patterns of recurrence. It has to be practical and relatively cost-effective. The major goals of such an algorithm for soft-tissue sarcomas would be early identification of potentially curable recurrences, identification of therapy-related complications, and patient reassurance.

Adult↗

PubMed1999

The role of chemotherapy in the treatment of adult soft tissue sarcomas.

Adult soft tissue sarcomas are relatively rare tumours which are curable with radical surgery. Approximately 50% of patients will develop inoperable disease or metastases for which chemotherapy may be appropriate. Only two cytotoxic agents - doxorubicin and ifosfamide - have activity in >20% of patients. For both these agents there is evidence of a dose-response relationship. There is currently no good evidence that combination chemotherapy confers a clinical benefit compared with single agents. Outside a clinical trial, standard first-line therapy should be with single agent doxorubicin at a dose intensity >/=70 mg2 every 3 weeks. Approximately 25% of patients may be expected to respond to this regimen. There is the suggestion that responses may occur to ifosfamide in patients who progress on doxorubicin. The role of chemotherapy in the adjuvant setting remains uncertain. Several trials have suggested a modest relapse-free and overall survival benefit for the use of post-operative chemotherapy and a recent overview of 14 randomised trials confirms a small though significant benefit. These benefits have to be weighed against the toxicity of chemotherapy. The importance of treating all patients with soft tissue sarcomas in clinical trials is stressed. There is an urgent need to define new active agents to treat this disease.

Adult↗

PubMed2000

Granulocyte colony stimulating factor permits dose intensification by interval compression in the treatment of Ewing's sarcomas and soft tissue sarcomas in children.

71 children with sarcomas were treated in a prospective pilot study to determine whether granulocyte colony stimulating factor (G-CSF) permits compression of the interval between chemotherapy cycles. Patients had Ewing's sarcoma/primitive neuroectodermal tumour (PNET), rhabdomyosarcoma, non-rhabdo soft tissue sarcomas or other advanced soft tissue tumours. The chemotherapy alternated vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide, with G-CSF between courses. Therapy had two phases: induction (six cycles) and continuation (six cycles), which included primary tumour treatment with surgery and/or radiation. Chemotherapy cycles began every 14 days, or upon absolute neutrophil count (ANC) and platelet count recovery. The median chemotherapy cycle interval was 16 (11-48) days in the induction phase, with a median average relative dose intensification (ARDI) of 1.27 compared with every-21-day therapy. In the continuation phase, the median cycle interval was 21 days, with a median ARDI of 1.10. Radiation therapy prolonged chemotherapy intervals, whilst erythropoietin shortened them. Toxicity was modest for such chemotherapy. Event-free survival is comparable with or superior to that in recent large studies. G-CSF permits intensification of this regimen through interval compression. The impact of this approach on efficacy remains to be determined in a randomised trial.

Adolescent↗

PubMed2004

[Differential diagnosis of soft tissue sarcomas].

INTRODUCTION: Soft tissue sarcoma often goes undetected. PATIENTS AND METHODS: Over a 10-year period, the patients referred to us with a soft tissue tumor (STT) of the extremities and wall of the trunk were analyzed retrospectively. The aim of the present study was to investigate the differential diagnoses, the number of incompletely operated STS, and local recurrences together with their percentage fluctuations. RESULTS: A total of 490 patients with an STT were referred to our department, and of these patients 55% were diagnosed with an STS. In addition to STS, the differential diagnoses for STT included 2% lymphomas, 18% isolated carcinoma metastases, 18% benign mesenchymal tumors, 5% inflammatory processes, and 2% old hematomas. Only 45% of the STS had not undergone previous surgery. Of these, 15% had been incompletely resected, while 39% of the STS patients were admitted with a local recurrence. Within the 10-year period, referrals with STT and STS remained relatively constant, but referrals of patients with incompletely resected or recurrent STS doubled in the last 2 years under observation. DISCUSSION: In view of the numerous differential diagnoses of an STT, both the possibility of an STS and also carcinoma manifestations in the soft tissues should receive more attention. With the aim of reducing the relatively high number of STS re-resections and local recurrences, the treatment of patients with suspicious STT should be reserved for a specialized center.

Abdominal Neoplasms↗

PubMed1991

The role of multimodality therapy in soft-tissue sarcoma.

Soft-tissue sarcomas are uncommon malignancies. The development during a period of 8 years, in one institution, of a prospective data base incorporating more than 1600 patients with these tumors is described. The most common sites for occurrence are the extremities, but they can occur in any of the soft tissues of the body. Liposarcoma and leiomyosarcoma are the most common histopathologic conditions identified. Prognostic factors for both recurrence and survival include site, histopathology, size, grade, and adequacy of resection. A prospective randomized trial of the use of adjuvant radiation by the brachytherapy technique in extremity lesions has shown a decrease in local recurrence, but no impact on survival. Eligible patients not randomized to the trial show no difference in local recurrence or survival, regardless of whether they received adjuvant radiation.

Adolescent↗

PubMedDate not supplied

Diagnosis, classification, and management of soft tissue sarcomas.

BACKGROUND: Soft tissue sarcomas are challenging to oncologists due to their unique character, the infrequency of their occurrence, and the difficulties in predicting outcomes. Advances in imaging, as well as improvements in surgical techniques and adjunctive treatment methods, have improved care for patients with these unusual disorders. METHODS: The various types of soft tissue tumors are defined, and the statistics for the Orthopaedic Oncology Group in relation to them are reviewed and compared with literature references. RESULTS: The overall survival rate for 1,220 tumors treated at our institute from June 1972 to June of 2001 was 72%, with a wide range. Patients with leiomyosarcomas, clear cell sarcomas, and malignant fibrous histiocytomas had a poorer survival rate, while those with fibrosarcomas, liposarcomas, and neurofibrosarcomas fared better. Outcome was affected by patient age, tumor anatomic site, tumor stage, and a history of recurrence. CONCLUSIONS: Competent imaging, predictive immunological and genetic studies, improved surgery, and newer methods of adjunctive and neoadjunctive treatment should result in improvements in outcomes for patients with these tumors.

Adolescent↗

PubMed2001

High Ki-67 proliferative index predicts disease specific survival in patients with high-risk soft tissue sarcomas.

BACKGROUND: Soft tissue sarcomas (STSs) are heterogeneous neoplasms that have variable clinical outcome. Several clinical parameters and few molecular markers, including Ki-67 proliferative index, have been shown to correlate with patient prognosis. To the authors' knowledge, no definitive report exists to identify one molecular marker that can be analyzed easily in a clinical setting and that predicts survival in a cohort of patients with high-risk STS of identical clinical characteristics but variable outcome. METHODS: The influence of clinical prognostic factors was eliminated by selecting two patient groups with identical high-risk characteristics: large (> 10 cm), high-grade, deep, completely resected primary extremity STS (n = 47). Patients in the first group remained disease free (no evidence of disease [NED]) after primary tumor treatment (n = 19), whereas patients in the second group subsequently died of disease (DOD; n = 28). Triplicate 0.6-mm core biopsies from defined morphologic areas of paraffin embedded primary tumors were assembled on a tissue microarray and analyzed by immunohistochemistry with the MIB-1 antibody, and Ki-67 proliferative indices were correlated with patient outcome. RESULTS: High Ki-67 proliferative index, defined as greater than 30% tumor cells showing nuclear immunoreactivity, was significantly more frequent in the DOD group than in the NED group and was associated with tumor-related mortality (P = 0.02). This marker identifies an especially aggressive malignant phenotype within a cohort of high-risk tumors that is based on well established clinical and pathologic parameters alone and is easy to use in a clinical setting. CONCLUSIONS: On the basis of these data and previous reports, high Ki-67 proliferative index is suggested as a significant factor for predicting the prognosis of patients with high-risk STS and should be evaluated prospectively based on clinical trials.

Adult↗

PubMed2005

Intratumor versus intertumor heterogeneity in gene expression profiles of soft-tissue sarcomas.

Soft-tissue sarcomas (STSs) constitute more than 30 histologic entities. In addition, within each entity, tumors are often heterogeneous in macroscopic features, genetic alterations, microscopic appearance, and clinical course. Therefore, there has been concern about whether a single tumor sample can provide a gene expression profile representative of the entire tumor. We used 27-k cDNA microarray slides to assess the importance of intratumor versus intertumor heterogeneity of the gene expression profiles of 2 morphologically heterogeneous STSs. Multiple pieces of tumor (8 and 10 pieces) were obtained from a myxoid variant of malignant fibrous histiocytoma (MFH) and a leiomyosarcoma (LMS), respectively, and the expression patterns were compared with single tumor samples from 20 MFHs and 16 LMSs. Hierarchical clustering analysis of the expression profiles showed that samples from the same tumor clustered together. The average intratumor distance was considerably shorter than the average intertumor distance in both LMS and MFH. In addition, tumor subclusters that distinguished different macroscopic parts of the tumor could be discerned. We concluded that intratumor variability exists but that accurate gene expression profiling also could be obtained using single samples from a large STS.

Adult↗

PubMed2003

Amputation for soft-tissue sarcoma.

Soft-tissue sarcomas are a group of rare malignant tumours, many of which arise in the limbs. Most are treated with a combination of wide local excision and radiotherapy, but a small number--including proximal, large, high-grade, or recurrent tumours, or those involving major neurovascular structures--necessitate major amputation including forequarter or hindquarter amputation. These uncommon operations should remain in the surgical armamentarium for carefully selected patients. Those being considered for amputation should be referred to a tertiary sarcoma unit for examination of all other options, such as limb-salvage surgery, tumour downstaging with chemotherapy or radiotherapy (perhaps with subsequent limb-salvage surgery), or novel techniques such as isolated limb perfusion. Only after careful assessment should amputation be carried out. Outcomes after major amputation are highly variable, but such procedures can confer useful palliation to patients with distressing symptoms (pain, bleeding, fungation), long-term disease-free survival with reasonable function in carefully selected patients, and cure in some.

Amputation, Surgical↗