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PubMed1998

Preoperative idoxuridine and radiation for large soft tissue sarcomas: clinical results with five-year follow-up.

BACKGROUND: Local control remains an important issue in the management of large soft tissue sarcomas. Radiation is the main adjuvant to surgery for local therapy of sarcomas, but it requires relatively high doses, hitherto considered prohibitive in areas such as the retroperitoneum. We developed a preoperative treatment approach to large soft tissue sarcomas that would deliver a high total dose of radiation administered in conjunction with the halogenated pyrimidine radiosensitizer idoxuridine (IdUrd). METHODS: Thirty-seven patients with large sarcomas of the head and neck, mediastinum, retroperitoneum, or extremity received three or five cycles of sequential IdUrd infusion (1000-1600 mg/m2/d x 5 d) alternating weekly with twice daily radiation (125-150 cGy per dose) and were then evaluated for resection. The delivered preoperative radiation dose was up to 6250 to 7500 cGy. RESULTS: Five patients (14%) had a partial response to preoperative therapy, and 28 of 37 patients underwent successful resection. There were no intra- or postoperative deaths. Local control was achieved in 19 of 28 resected patients, but in only 1 of 6 patients who remained unresectable despite therapy. With a median follow-up of 5.8 years, 28% of patients are alive with no evidence of disease, 17% are alive with disease, and 53% have died of their disease. CONCLUSIONS: Using the dose and schedule we employed, resection of large soft tissue sarcomas was possible after high-dose radiation delivered in conjunction with IdUrd. Although local control was acceptable, the high rate of distant failure represents a limitation of any local approach to the treatment of large soft tissue sarcomas and suggests the need for integration of this approach with an effective systemic therapy.

Adolescent↗
PubMedDate not supplied

Combined modality treatment of extremity soft tissue sarcomas.

BACKGROUND: Substantial progress has been made in the multimodality treatment of soft tissue sarcoma over the past decade. This review summarizes current state-of-the-art management for patients with extremity soft tissue sarcoma. METHODS: Literature-based review of combined modality treatment of extremity sarcoma. RESULTS: The revised staging system of the International Union Against Cancer/American Joint Committee on Cancer (UICC/AJCC) for this disease is described and a practical approach to diagnosis, evaluation, management, and follow-up of patients is presented. Brief summaries of the roles of surgical therapy, pre- and postoperative radiotherapy, pre- and postoperative chemotherapy, and concurrent chemoradiation in the management of extremity soft tissue sarcoma are provided, with summaries of the available data from randomized prospective trials. The data referenced and discussed herein provide the basis for stage-specific treatment recommendations for the management of patients with localized soft tissue sarcoma of the extremities. CONCLUSIONS: Soft tissue sarcoma remains a challenging disease to treat. The majority of patients require an integrated combined modality approach. Future research should be directed at developing more effective systemic therapies and minimizing the toxicities of local therapies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1982

Primary pulmonary sarcomas: etiology, clinical assessment and prognosis with a comparison to pulmonary carcinomas--a review of 41 cases and 394 other cases of the literature.

Primary sarcomas of the lungs occur at frequencies of 1:100, as compared with carcinomas reported in our retrospective studies covering 394 cases reported in the literature from 1957 to 1972 and 41 cases from 1957 to 1974. The average age was 45 years, the disease usually occurred between the ages of 35 and 65, the peak being between 45 and 60 years. Distribution between sexes was much the same as that seen in general. X-ray with rapid thoracotomy provided the best clinical results. The literature showed a postoperative survival time of 5 years in 19% and 44% of our own cases. The general metastasis, haematologenous and lymphogenous were more or less equal and recidive tendency in 7% essentially varied, as related to the single histological forms. Lymphosarcomas (28.6%) were the most frequent, the group of spindle-celled sarcomas, inclusive of leiomyosarcomas, occurred in 40%. Histological maturity of the tissues and the prognosis according to active therapy were in parallel. A comparison of 41 primary sarcomas of the lungs with the 192 cases of carcinomas seen in our clinic showed no connection between sarcomas of the lungs and smoking of cigarettes, pollution of the environment, industrial toxins or chronic bronchitis. These findings relate to the peripheral localization as well as to the lack of incidence among men, with regard to pulmonary adenocarcinomas. An overall view of the characteristics led to the assumption of a probable endogenous tumour. A summarization of the characteristics of pulmonary sarcomas and carcinomas revealed the role of primary sarcomas in the total complex of malignant tumours of the lungs.

Adolescent↗
PubMed1991

Soft tissue and visceral sarcomas in Irish patients. A preliminary report from the Dublin Soft Tissue Tumour Panel.

Sarcomas of the soft tissues and viscera are a diverse group of uncommon neoplasms that often present difficult diagnostic and management problems. The Dublin Soft Tissue Tumour Panel prospectively reviewed pathology material from 137 patients of four Dublin teaching hospitals between January 1989 and August 1990. The prevalence of sarcomas in Irish patients was found to be similar to that estimated for the United States. The most common sarcoma of soft tissues was malignant fibrous histiocytoma (14) and the most common visceral sarcoma was leiomyosarcoma (10). The most problematic diagnoses were 3 peripheral neuroepitheliomas (extraskeletal Ewing's sarcomas) which occurred in patients aged 19-27 years, distinctly younger than the typical adult sarcoma patient. Clinical follow-up is in progress and will be combined with the findings of a linked retrospective study, to facilitate evaluation of all aspects of management.

Abdominal Neoplasms↗
PubMed1999

Treatment results of fast neutron irradiation in soft tissue sarcomas.

PURPOSE: Surgery is the standard treatment of soft-tissue sarcomas. Adjuvant radiotherapy with photons after less radical resection can improve local control. The rate of tumor control achieved in patients with G1 and G2 soft tissue sarcomas incompletely resected and treated postoperatively with neutron irradiation is similar to that seen in patients undergoing complete tumor resection and adjuvant photon irradiation. PATIENTS AND METHODS: At the Department of Radiotherapy and Radiation Oncology of the University of Münster, 61 patients with soft tissue sarcomas were irradiated postoperatively with fast neutrons. Mainly tumors of low or intermediate malignancy (R0; 27%; R1, 21%; R2, 52%) were treated. Malignant fibrous histiocytoma, liposarcoma, and neurogenic sarcomas dominated. 46 patients were irradiated with fast neutrons alone, and 15 patients were treated with mixed beam therapy (photons and neutrons). RESULTS: The median follow-up period was 44 months. Overall five-year survival probability analysed by Kaplan-Meyer method was 42.5%. The local control rate was 57.7%. 15 patients showed complete remission, 18 patients had a partial remission. Only 11% of the patients showed grade III and IV side effects during neutron irradiation. CONCLUSION: Neutron irradiation is efficocious in treating highly and intermediately differentiated soft tissue sarcomas. The result of surgical resection seems to be a very important prognostic factor for patients with soft tissue sarcomas.

Adult↗
PubMed2000

[Soft tissue sarcoma: prognostic factors and multimodal treatment].

Soft-tissue sarcomas are a relatively rare disease accounting for approximately 1% of adult malignancies. Various different histological subtypes exist that behave similarly regarding their biological characteristics and response to treatment. Soft-tissue sarcomas occur in up to 50% of cases in the extremities, followed by visceral/retroperitoneal and trunk tumors. Primary therapy is predicated on surgical resection with an adequate margin of normal tissue. Limb-sparing surgery for extremity lesions is possible in more than 90% of patients. For high-risk patients, identified by tumor grade, size and site, local control is improved with postoperative adjuvant radiation. Local recurrence rates vary, depending on the anatomic site. In the most common extremity lesions, one-third of the patients develop locally recurrent disease with a median disease-free interval of 18 months. For visceral sarcomas recurrence rates are up to 40-50%. Treatment results for extremity local recurrences may approach those for primary disease. Metastases of extremity sarcomas predominantly spread to the lungs where isolated metastases can be resected with 20-30% 3-year survival rates. Patients with unresectable pulmonary metastases or extra-pulmonary metastatic sarcoma have a uniformly poor prognosis and are best treated with systemic chemotherapy. In general, optimal treatment of soft-tissue sarcoma requires individual care tailored to the single patient.

Adolescent↗
PubMed1998

[Ewing sarcoma. Diagnostic imaging].

Ewing's sarcoma is a highly malignant neoplasm of the bone whose origin is still uncertain. A strong relationship exists between Ewing's sarcoma and tumors of neural origin (Ewing family of tumors). Ewing's sarcoma must be distinguished from other round-cell tumors like lymphoma and neuroblastoma and also must be differentiated from osteogenic sarcomas. On plain radiographs, Ewing's sarcoma appears as a lytic or mixed lytic-sclerotic, rarely as predominantly sclerotic lesion with margins Lodwick grade III. It is located primarily in the diaphyseal and metadiaphyseal regions of the long bones of the lower extremities. A large soft tissue tumor is usually present. Magnetic resonance imaging is the imaging modality of choice to evaluate the extent of the primary lesion, to monitor the response to neoadjuvant chemotherapy and to follow up non-resected Ewing's sarcomas. Bone scintigraphy is necessary to detect skeletal metastasis, and 201thallium scanning has been shown to be sensitive in the monitoring of treatment response. Today, computed tomography is not longer used to image the tumor site; however, spiral CT of the lungs plays a central role as a staging and follow-up tool.

Bone Neoplasms↗
PubMed2002

Treatment of bone and soft tissue sarcomas of the hand and wrist.

We studied 13 consecutive patients with bone and soft tissue sarcomas of the hand and wrist. Chondrosarcoma, Ewing's sarcoma, synovial sarcoma and epithelioid sarcoma were the most frequent histological diagnoses. Limb-sparing surgery was performed in ten patients but eventually three patients required an amputation. Surgical margins were wide in nine patients and marginal in four. Adjuvant therapy for nine patients consisted of chemotherapy in five and chemotherapy with radiation in four. Local recurrence occurred in two patients with epithelioid sarcoma. There was no significant relationship between surgical margin and local recurrence. Distant metastasis occurred in four patients. The 5-year survival rate was 66%. The mean functional score was 87%. Our study indicates that treatment consisting of resection of these tumours with either a wide margin or a marginal margin followed by adjuvant radiation appeared to be safe and resulted in an acceptable degree of limb function except in the patients with epithelioid sarcoma.

Adolescent↗
PubMed1996

[Pathology of Ewing sarcoma].

Ewing's sarcoma is a very rare tumor which has, however, attracted much oncological interest since the dramatic improvement of its prognosis under chemotherapy. Its histogenesis has been discussed controversially for a long time, including a possible origin in immature reticulum, myogenous, endothelial and undifferentiated mesenchymal cells. Repeated reports have also suggested a possible neuroectodermal genesis. Convincing arguments, however, have only been brought forward during recent years, since it was found that Ewing's sarcoma and malignant peripheral neuroectodermal tumor share a common chromosome translocation 11;22. In the meantime this hypothesis has been strengthened by numerous cell biological analyses. There seems to be no clear border between Ewing's sarcoma and malignant peripheral neuroectodermal tumors with definite neural differentiation. Histological differential diagnosis of Ewing's sarcoma has been improved by immunohistological methods. In most cases, they can be distinguished from lymphoma (leucocyte common antigen, B and T markers) and embryonal rhabdomyosarcoma (muscle specific actin, desmin) without problems. Apart from that, it is possible nowadays to obtain antibodies against the MIC 2-protein, which is preferably expressed in Ewing sarcoma. The diagnostics of Ewing's sarcoma and the malignant peripheral neuroectodermal tumor have considerably been enriched by the fact that the specific chromosome translocation t(11;22) can be proved molecular biologically. In contrast to the cytogenetic evidence, it is not necessary to establish cell cultures.

Biomarkers, Tumor↗
PubMed2001

Expression of cadherins and their undercoat proteins (alpha-, beta-, and gamma-catenins and p120) and accumulation of beta-catenin with no gene mutations in synovial sarcoma.

E-cadherin, the major intercellular adhesion molecule of epithelial cells, is important in determining the architecture of sarcomas, especially those showing epithelioid features. In addition to its role in cell adhesion, beta-catenin, a cadherin undercoat protein, has been shown to function as a downstream transcriptional activator of the Wnt/Wingless signaling pathway. In order to evaluate the significance of the cadherin cell adhesion system and the Wnt/Wingless signaling pathway in the morphogenesis and/or tumorigenesis of synovial sarcoma (a major type of sarcoma with epithelioid features), immunoreactivity for pan-cadherin, E-cadherin, and their undercoat proteins (alpha-, beta-,and gamma-catenins and p120) was evaluated in 15 synovial sarcomas. Immunoreactivity for pan-cadherin, E-cadherin, alpha-catenin, beta-catenin, and p120 was observed in all 15 specimens. Immunoreactivity for pan-cadherin was stronger than that for E-cadherin. Expression of gamma-catenin was detected in ten specimens. Although beta-catenin was observed only at the cell-cell boundaries in four specimens, it was present in the nucleus and cytoplasm and at the cell-cell boundaries in the other 11, suggesting constitutional activation of the Wnt/Wingless signaling pathway in synovial sarcoma. Direct sequencing for exon 3 of the beta-catenin gene, however, revealed no mutations in any of the 15 specimens. In conclusion, other types of cadherin besides E-cadherin, together with cadherin undercoat proteins, may play a role in cell adhesion in synovial sarcoma. Furthermore, mechanisms other than mutation of exon 3 of the beta-catenin gene may activate the Wnt/Wingless signaling pathway in this type of tumor.

Adolescent↗
PubMed1998

Specific and sensitive detection of the EWS/FLI1 fusion protein in Ewing's sarcoma by Western blotting.

We applied Western blotting, using an antibody against the carboxy terminal of the FLI1 protein, for detection of the 68-kDa EWS/FLI1 fusion protein in cultured Ewing's sarcoma cells and in four surgical biopsies of Ewing's sarcoma. Of six different human cell lines, the 68-kDa fusion protein was identified only in Ewing's sarcoma cells carrying the t(11;22)(q24;q12) translocation. The four samples from Ewing's sarcoma patients were also found to contain the 68-kDa fusion protein. The lowest detection level for total protein loaded on the gel was 0.3 microg. When whole Ewing's sarcoma cells were used for Western blotting without prior protein extraction, the lowest detection level was 1,300 cells. It will be possible to use Western blotting for detection of the EWS/FLI1 fusion protein in the diagnosis of Ewing's sarcoma in surgical biopsy specimens, and possibly also in fine-needle aspirates. As the method is not dependent on the quality of mRNA in the sample and involves no risk of contamination, it will be a powerful complement to the reverse-transcription polymerase chain reaction (RT-PCR).

Blotting, Western↗
PubMed2001

Identification of syt-ssx fusion transcripts in both epithelial and spindle cell components of biphasic synovial sarcoma in small tissue samples isolated by membrane-based laser microdissection.

In order to confirm the presence of SYT-SSX fusion gene in epithelial and spindle cell components of synovial sarcoma, we performed a nested reverse transcriptase-polymerase chain reaction (RT-PCR) using microbeam microdissection of membrane-mounted native tissue (MOMeNT) technique applied on formalin-fixed, paraffin-embedded tumor specimens from two biphasic synovial sarcomas and a control tissue of adamantinoma. Small targeted portions of either an epithelial or spindle cell component of the tumor tissue were microdissected together with the supporter membrane, by using an ultraviolet (337-nm) pulsed laser microbeam coupled into a robot-stage microscope with infinity optics. The SYT-SSX fusion transcript was detected in epithelial and spindle cell components of both biphasic synovial sarcomas, but not in the control tissue. Southern blot analysis also confirmed that the detected messages were derived from the SYT-SSX fusion gene. In conclusion, the microbeam MOMeNT is a useful method for isolating selected small portions from tissue sections. The SYT-SSX fusion gene is present in both cellular components of biphasic synovial sarcoma and is involved in oncogenesis of the synovial sarcoma rather than in morphologic epithelial differentiation. Therefore, in spite of the variable proportions of each component, our results confirm that the synovial sarcoma is of monoclonal origin.

Adult↗
PubMed2005

Strategies and methodologies for identifying molecular targets in sarcomas and other tumors.

Sarcomas are a heterogeneous group of tumors that respond poorly to conventional cytotoxic chemotherapy. Sarcomas possess specific molecular characteristics that exist because of unique somatic mutations, vital growth factor or growth factor receptor overexpression, or are critically dependent on host pathways. Currently these tumors are classified on the basis of their tissue of origin and histologic appearance. Gene expression and proteomic analysis of sarcomas may enable reclassification of these tumors and help predict their biologic behavior and devise common therapeutic strategies within a class. It may not be long before cDNA/protein expression profiling and karyotyping complement the current standard pathological evaluation of a newly diagnosed sarcoma, thereby helping the clinician pick targeted agent(s) relevant to the expression profile. The spectacular success of imatinib in patients with gastrointestinal stromal tumor demonstrates how molecular targeting can fulfill the promise of low toxicity and high response rates. Finding new targets, and learning how to use the current generation of targeting drugs in sarcoma, are urgent challenges. Therapeutic clinical trials with a host of new molecular-targeting agents are underway that will drive new paradigms in sarcoma therapeutics. Patients with refractory disease who currently have no viable therapeutic options may have options that open up with the advent of newer targeted approaches, converting their disease from an acute short-lived one to a chronic process with preservation of quality of life while receiving therapy.

Angiogenesis Inhibitors↗
PubMed1982

Immunologic abnormalities in homosexual men. Relationship to Kaposi's sarcoma.

Studies were performed to define the immunologic status of various groups of homosexual men including homosexual men with Kaposi's sarcoma, healthy homosexual men who were of similar ages to the homosexual patients with Kaposi's sarcoma and homosexual men with hyperplastic lymphadenopathy. Heterosexual men with Kaposi's sarcoma were also studied. Immunologic parameters which were examined included serum immunoglobulin levels, enumeration of B cells, T cells, and T-cell subsets, and quantitation of lymphocyte responsive to phytohemagglutinin (PHA) and pokeweed mitogen (PWM). Significant immunologic abnormalities were observed in all three groups of homosexuals studied. These were most severe in the homosexuals with Kaposi's sarcoma, somewhat less severe in homosexual men with lymphadenopathy, and least marked but still significant in healthy homosexual men. Heterosexual men with Kaposi's sarcoma displayed essentially normal immunologic profiles. The possible etiologic factors underlying the immunologic abnormalities in the male homosexual population studied and the role of an altered immune system in the development of and the fulminant course of Kaposi's sarcoma in these patients are discussed.

Homosexuality↗
PubMed1986

Pulmonary Kaposi's sarcoma in the acquired immune deficiency syndrome. Clinical, radiographic, and pathologic manifestations.

Pulmonary Kaposi's sarcoma related to the acquired immune deficiency syndrome (AIDS) has not been well characterized. To define the clinical, radiographic, and pathologic features of this entity, 11 autopsy-proved cases of pulmonary Kaposi's sarcoma were reviewed. The most common clinical symptoms were dyspnea and cough, but hemoptysis and stridor were also found. Nodular infiltrates and pleural effusions were the most commonly found radiographic abnormalities. Pulmonary function tests were sensitive in detecting the pulmonary abnormalities due to Kaposi's sarcoma. A low diffusion capacity, lack of arterial desaturation with exercise, and obstruction to airflow were suggestive of pulmonary involvement with this malignancy. Although endobronchial Kaposi's sarcoma was visualized at bronchoscopy as cherry-red, slightly raised lesions, bronchial biopsy specimens always showed no abnormalities. Transbronchial brushings and biopsy specimens and analysis of pleural fluid were also not helpful in establishing a diagnosis. In the seven subjects with extensive parenchymal Kaposi's sarcoma at autopsy, the pleura was always involved. Eight subjects had involvement of the tracheobronchial tree. In all of the subjects, pulmonary Kaposi's sarcoma was a significant cause of morbidity, and in three of 11 subjects (27 percent) it was the direct cause of death.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Kaposi's sarcoma: the most common tumor after renal transplantation in Saudi Arabia.

Between September 1975 and November 1986, 263 renal transplant recipients at the King Faisal Specialist Hospital and Research Center were followed; 82 procedures were done by the authors using live related donors. Among the 263 patients, 14 cases of Kaposi's sarcoma were identified, an incidence of 5.3 percent compared with an incidence of 0.4 percent in renal transplant recipients from Western countries. In addition, two more patients had other types of tumors. Thus, Kaposi's sarcoma represents 87.5 percent of tumors in the King Faisal Hospital renal transplant population, in contrast to 3.7 percent in the Cincinnati Transplant Tumor Registry. The mean period between transplantation and diagnosis of Kaposi's sarcoma was 12.5 months (range, one to 37 months). Eleven patients were Saudis and three were other Arab nationals. Seven of the 11 Saudi patients were from the southwestern region of the country. Cytomegalovirus titers were not elevated in six of 10 patients. Results of tests for human immunodeficiency virus were negative in seven of eight patients. HLA-A2 antigen frequency was significantly increased in the King Faisal Hospital renal transplant patients with Kaposi's sarcoma as compared with a control population (83.3 percent versus 43.6 percent, p value = 0.006 [P = 0.06 with Bonferroni adjustment]), and increased, though nonsignificantly, compared with the live related kidney transplant recipients without Kaposi's sarcoma (83.3 percent versus 49.4 percent, p value = 0.058 [P = 0.58 with Bonferroni adjustment]), suggesting a genetic predisposition to Kaposi's sarcoma in these patients.

Adult↗
PubMed1994

Primary sarcoma of the lung: a clinical study with long-term follow-up.

Primary pulmonary sarcoma is an extremely rare tumor. In more than 30 years, only 22 patients with PPS were seen in our hospital; 18 patients (82%) underwent operation. Radical resection is the only curative treatment in patients with primary pulmonary sarcoma. All 4 patients (18%) who did not undergo operation died within 17 months. All 7 patients (32%) in whom no radical resection could be performed died between 10 months and 16 years after operation. Total resection of the tumor could be performed in 11 patients (50%). Of these, 7 are still alive (64%), and 1 patient died of an unrelated cause after 25 years (mean follow-up, 13.5 years). Histologic diagnosis in these patients was leiomyosarcoma in 4, malignant schwannoma in 2, and fibrosarcoma and undifferentiated sarcoma in 1 each. Median survival for all patients was 24 months. Actuarial 5-year survival was 44% for all patients. Small tumor diameter and low-grade malignancy are statistically significant favorable prognostic factors. No patient with grade 1 tumor died; the median survival was 60 months for grade 2 sarcomas, and 17 months for grade 3 sarcomas. No patient with a completely resected small primary pulmonary sarcoma had recurrence or metastasis.

Adolescent↗
PubMed1989

Frequency and distribution of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced structural chromosome aberrations in fibroblasts from sarcoma and non-Hodgkin's lymphoma patients.

The frequency and distribution of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced structural aberrations, i.e., chromatid and chromosome gaps, breaks, and exchanges, were studied in fibroblasts from 16 patients with sarcoma, 15 with non-Hodgkin's lymphoma (NHL), and 14 controls. The mean frequencies of aberrant cells, and gap, break, and gap + break events per 100 cells were 22.9, 5.1, 28.6, and 33.7 in the sarcoma group; 19.1, 5.0, 22.5, and 27.5 in the NHL group; and 23.5, 6.1, 33.5, and 39.6 in the control group. None of the differences between the groups were statistically significant. The distribution of MNNG-induced aberrations was non-random (P less than 0.001) in all 3 groups. Eight, 11, and 17 chromosome bands in the sarcoma, NHL, and control groups, respectively, were particularly break-prone. Only 2 hot spots in the sarcoma group (1p32, 11q23), and 3 in the NHL group (1p36, 3q25, 6p21), coincided with the 25 and 60 bands known to be involved in primary rearrangements in sarcomas and NHL. We conclude that neither the frequency nor the distribution of MNNG-induced chromosomal aberrations indicates any latent chromosomal instability in sarcoma and NHL patients.

Chromosome Aberrations↗