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PubMed2001

Increased risk of soft tissue sarcoma after radiotherapy in women with breast carcinoma.

BACKGROUND: Numerous studies to date have suggested an association between radiation exposure and the development of soft tissue sarcoma. The current study was performed to quantify the risk of soft tissue sarcoma in the vicinity of previously irradiated anatomic regions in women with breast carcinoma. METHODS: In this population-based, retrospective cohort study, 194,798 women who were diagnosed with invasive breast carcinoma (exclusive of those with distant metastasis) between 1973--1995 were identified, and subsequent soft tissue sarcoma cases utilizing the data from the Surveillance, Epidemiology, and End Results Program (SEER) were ascertained. Poisson regression analysis was used to calculate age standardized incidence ratios (SIR) and to model the influence of radiotherapy (RT) on the relative risk (RR) between the RT and non-RT cohorts. RESULTS: A total of 54 women in the RT cohort and 81 women in the non-RT cohort subsequently developed soft tissue sarcoma. In the RT cohort, the SIR was 26.2 (95% confidence interval [95% CI], 16.5--41.4) for angiosarcoma and was 2.5 (95% CI, 1.8--3.5) for other sarcomas; in the non-RT cohort, the SIRs were 2.1 (95% CI, 1.0--4.4) and 1.3 (95% CI, 1.0--1.7), respectively. The RT cohort demonstrated a higher risk of developing both angiosarcoma (RR: 15.9; 95% CI, 6.6--38.1) and other sarcomas (RR: 2.2; 95% CI, 1.4--3.3) compared with the non-RT cohort, and the largest increase was observed in the chest wall/breast. The elevated RR was significant even within 5 years of RT, but it reached a maximum between 5--10 years. CONCLUSIONS: The risk of soft tissue sarcoma, especially angiosarcoma, was elevated after RT in women with breast carcinoma.

Adult↗
PubMed2002

Concordance of histopathologic and cytologic grading in musculoskeletal sarcomas: can grades obtained from analysis of the fine-needle aspirates serve as the basis for therapeutic decisions?

BACKGROUND: Utilization of fine-needle aspiration (FNA) for the diagnosis of musculoskeletal lesions has been de-emphasized by many clinicians because of concerns regarding the technique's ability to supply all information necessary for prognostication and appropriate selection of therapy. Paramount among the concerns is the belief that FNA is incapable of supplying precise subtyping and grading in many cases. Secondary concerns regarding the use of FNA involve its perceived inability to supply adequate tissue for ancillary studies including immunohistochemistry and molecular diagnostic analysis. The authors investigated the ability of FNA to accurately subtype and grade a series of 107 primary sarcomas of the musculoskeletal system. METHODS: The files of the Departments of Pathology at Duke University Medical Center and the University of California at Los Angeles and the private consultation files of one of the authors were searched for all fine-needle aspirates of sarcomas arising within the musculoskeletal system. A total of 107 cases were obtained and reviewed by three board-certified cytopathologists. Each cytopathologist independently assigned subtype when possible and generated a grade for each of the sarcomas. Corresponding surgical material was available for 77 cases. The surgical material was re-reviewed for accuracy of diagnosis and assignment of grade independently of the cytologic examination. Correlation of cytologic grade with histopathologic grade was made and analyzed by the kappa test. In addition, agreement on grade between cytopathologists was analyzed, and accuracy of histologic subtype prediction by cytologic analysis was studied. RESULTS: Most of the sarcomas were cytologically graded as Grade 1 or 2 but were assigned a histologic grade of 2 or 3. Cytopathologist A graded 93% of the sarcomas as either Grade 1 or 2, cytopathologist B graded 89% of cases as Grade 1 or 2, and cytopathologist C graded 94% of cases as Grade 1 or 2. Histologic evaluation demonstrated 82% of cases to be Grade 2 or 3. Correlation of cytologic and surgical grade varied among the observers. Cytopathologist A showed the highest degree of correlation between cytologic and surgical grade with an r value of 0.5. The corresponding r values for cytopathologists B and C were 0.46 and 0.41, respectively. Correlation between cytologic and surgical grade was significant for all three observers (P < 0.001). Only nuclear grade showed a consistent correlation in predicting final surgical pathology grade. Cellularity, mitotic rate, and the presence of necrosis were not statistically significant for predicting histopathologic grade. Accurate exact subtyping by cytologic examination was achieved in approximately 55% of cases. Prediction of histopathologic subtype by cytologic analysis was most successful when a distinctive stroma was present or high-grade features indicative of malignant fibrous histiocytoma were observed. There was little agreement as to histopathologic type as predicated by cytology for low-grade spindle cell sarcomas. CONCLUSIONS: Although there was a statistically significant correlation between cytologically assigned grade and final histopathologic grade, statistical analysis revealed only a moderate correlation between the two with an overall r value of approximately 0.57. Cytologic analysis tended to undergrade in comparison to final histopathologic grading. Only analysis of nuclear atypia showed good correlation with final surgical grade. Fine-needle aspiration was only moderately successful at predicting histopathologic subtype for musculoskeletal sarcomas in this series.

Adult↗
PubMed2005

Radiation-induced sarcomas after radiotherapy for breast carcinoma: a large-scale single-institution review.

BACKGROUND: Sarcomas are a rare complication of radiotherapy for breast carcinoma and patients have a poor prognosis. The incidence, histology, and management of patients with sarcomas were reviewed in the current study. METHODS: The authors reviewed the records of 16,705 patients with breast carcinoma. Of these, 13,472 (81%) were treated with megavoltage radiotherapy and 3233 were treated without at the Institute Curie (Paris, France) between 1981 and 1997. Median doses of 50-55 grays (Gy) in 25-27 fractions were delivered to the whole breast over a period of 5-5.5 weeks (2 Gy/day, 5 weekly fractions) followed, when indicated, by a 16-26-Gy boost to the tumor or tumor bed. Treatment of radiation-induced sarcomas (RIS) consisted mostly of radical surgery and chemotherapy. RESULTS: Overall, 35 patients developed sarcomas. Of these, 27 fulfilled the Cahan criteria. The median follow-up was 9.3 years (range, 1-22.4 years). The latency period ranged from 3 years to 20.3 years. Thirteen sarcomas were located in the breast, 5- in the chest wall, 3 in the sternum, 2 in the supraclavicle, 1 in the scapula, and 3 in the axilla. Histologic evaluation identified 13 angiosarcomas, 3 osteosarcomas, 5 undifferentiated sarcomas, 1 malignant fibrous histiocytoma, 2 leiomyosarcomas, 1 fibrosarcoma, 1 rhabdomyosarcoma, and 1 myosarcoma. The cumulative RIS incidence was 0.07% (+/- 0.02) at 5 years, 0.27% (+/- 0.05) at 10 years, and 0.48% (+/- 0.11) at 15 years. Standardized incidence ratios were 10.2 (95% confidence interval, 9.03-11.59) for irradiated patients and 1.3 (0.3-3.6) for nonirradiated patients. Of the 27 patients, 15 died of sarcoma within 1 month to 14.5 years (mean, 34.2 +/- 0.7 months). The 5-year actuarial survival rate after diagnosis of RIS was 36% (+/- 0.11). CONCLUSIONS: The current study confirmed the rarity of RIS. However, it showed that the risk increased with time. Therefore, careful, long-term follow-up of patients treated with radiotherapy is needed for early detection and efficacious treatment of these malignancies.

Adult↗
PubMed2001

Mutagen sensitivity as an indicator of soft tissue sarcoma risk.

The etiology of soft tissue sarcoma is poorly understood. Exposure to environmental chemicals may play a role, but the data are not clear. We compared a group of soft tissue sarcoma patients with healthy controls to determine whether the mutagen sensitivity assay, a simple chromosome aberration assay using the radiomimetic bleomycin, might be useful to identify patients at risk for soft tissue sarcoma. Patients with a diagnosis of soft tissue sarcoma at Memorial Sloan-Kettering's outpatient clinic signed informed consent and donated 30 ml of blood. Controls were selected from the general population of Connecticut by random digit dialing. Unrepaired DNA damage was assessed for 100 metaphase spreads for each individual, with the number of breaks in chromatids being counted as breaks per cell (b/c). The 20 cases with soft tissue sarcoma had 1.03 mean b/c and the controls had 0.88 b/c (P = 0.16). Patients with soft tissue sarcoma were 5.7 times more likely to be mutagen sensitive than controls (P = 0.01), as determined after dividing subjects into sensitive or not sensitive groups based on the median b/c among controls. As mutagen sensitivity has been shown to be associated with a number of cancers and appears to reflect genetic susceptibility, this assay may be an appropriate biomarker for radiation sensitivity or it may be a marker of susceptibility to soft tissue sarcoma. Larger studies should be undertaken to assess these possibilities.

Adult↗
PubMed1976

Inflammatory cells in solid murine neoplasms. II. Cell types found throughout the course of Moloney sarcoma regression or progression.

Regressing and progressing Moloney sarcomas, induced in BALB/c mice by the injection of cultured sarcoma cells (MSC)1, were sampled for histologic analysis and then disaggregated using mixtures of trypsin, collagenase and DNAse or collagenase and DNAse alone. The types of inflammatory cells (IC) found in resultant cell suspensions were determined 6, 11, 14 and 18 days post inoculation. Inflammatory infiltrates were composed almost exclusively of three cell types; neutrophils, T lymphocytes and macrophages. The extent to which each was found in tumors was related to the time post inoculation. Neutrophils were part of an early acute inflammatory response seen in both developing regressing and progressing sarcomas. The onset of regression was associated histologically with the appearance within tumors of a mononuclear inflammatory infiltrate. T lymphocytes and macrophages were the principal constituents. A higher percentage of T lymphocytes was recovered at all sampling times from regressing, compared to progressing, sarcomas. During development of the mononuclear inflammatory infiltrate there were relatively more large T cells in regressing, than in progressing tumors, and the percentage of macrophages was higher. Thereafter, the proportion of macrophages in the recovered cell population was approximately the same for both types of tumor. Such equality was more apparent than real, however, since IC were restricted to the peripheries of progressing sarcomas after the acute inflammatory phase, but continued to be found throughout regressing neoplasms. The effective ratio of macrophages and T lymphocytes to tumor cells therefore was much lower in progressing sarcomas than was suggested by percentage figures. The data presented support the concept that T lymphocytes are instrumental in causing the regression of Moloney sarcomas, possibly through interactions with macrophages.

Animals↗
PubMed1979

Cell-mediated reactivity to antigens shared by Moloney-virus-induced lymphomas (LSTRA) and certain 3-methylcholanthrene-induced mouse sarcomas.

Spleen cells (SC) both from BALB/c mice whose primary Moloney sarcoma virus (MSV)-induced sarcomas had spontaneously regressed and from normal, untreated BALB/c mice, were co-cultivated for 5 days with mitomycin-C-treated LSTRA cells; LSTRA is a BALB/c Moloney lymphoma which shares cell surface antigens with MSV-indiced sarcomas. These SC, referred to as CMR and CU cells, respectively, were shown to be cytotoxic to LSTRA cells in 3 h 51Cr-release assays; CMR cells showed, in most cases, the greatest lytic activity against LSTRA targets. The same SC were also reactive, in 20-h microcytotoxicity and 51Crassays, against target cells from a variety of transplanted sarcomas indiced by 3-methylcholanthrene (MCA) in Balb/c mice. The highest reactivity was seen when CMR or CU cells were tested against target cells from sarcoma lines that expressed an NB-ecotropic MuLV cross-reacting serologically with Moloney virus. Reactivity against isotope-labelled tumor cells expressing MuLV-associated cell surface antigens could be competititively inhibited by adding unlabelled tumor cells expressing such antigens. Finally, Winn assays were performed in which CMR cells strongly inhibited the outgrowth of cells from three sarcoma lines that express the NB-ecotropic MuLV. There was less but significant inhibition of cells from some other MCA sarcomas, either negative for the expression of MuLV-associated antigens or expressing the N-ecotropic endogenous BALB/c MuLV. CU cells enhanced tumor outgrowth in Winn assays at least as often as they inhibited it.

Animals↗
PubMed1990

Elevated frequency of a specific allele of the L-myc gene in male patients with bone and soft-tissue sarcomas.

Restriction fragment length polymorphisms (RFLPs) of 2 oncogenes, c-Ha-ras and L-myc, have been analyzed in 101 patients with bone and soft-tissue sarcoma and in 98 normal individuals. The c-Ha-ras gene was highly polymorphic both in sarcoma patients and in normal individuals. In contrast to our previous observation in breast cancer patients (Honda et al., 1988), no significant difference in allele frequencies between normal and sarcoma populations was observed. The L-myc locus revealed 2-allele polymorphism, allele L (10-kb) and S (6.6-kb), after digestion with Eco RI. The allele frequencies of L and S in sarcoma patients were 0.381 and 0.619, respectively, and those in normal individuals were 0.485 and 0.515, respectively. While the distributions of alleles in both populations fitted well with the Hardy-Weinberg equilibrium, the frequency of the S allele was significantly higher in sarcoma patients than in normal individuals (p less than 0.05). When sarcoma patients were divided into male and female subpopulations, this difference was highly significant only in males (p less than 0.01) but not in females. Our results suggest that males carrying the S allele may be prone to develop sarcoma.

Alleles↗
PubMed1988

Immortalization of human endothelial cells by murine sarcoma viruses, without morphologic transformation.

Amphotropic murine leukemia virus pseudotypes of murine sarcoma viruses containing the ras or mos oncogenes were constructed to permit efficient introduction of the sarcoma virus genome into early-passage human umbilical vein endothelial cells. The resulting cell lines were morphologically and phenotypically unchanged, retaining properties characteristic of differentiated endothelial cells. For example, the cells in a Kirsten sarcoma virus-modified line were found to biosynthesize and secrete von Willebrand factor in both a constitutive and regulated manner, and they contained ultrastructurally identifiable Weibel-Palade bodies, an endothelial cell-specific organelle. In contrast to the parent cultures, sarcoma virus-modified cells were able to proliferate indefinitely in culture. Examination of both Kirsten sarcoma and Moloney leukemia virus-modified lines indicated that the immortalized cells retained a diploid female karyotype after over 18 months in culture. In addition, the sarcoma virus-modified cells were able to grow independently of added endothelial cell growth factor. This growth factor autonomy does not appear to be due to autocrine production of a biologically cross-reactive growth factor. These immortal, virus-modified endothelial cells express large amounts of sarcoma virus-specific mRNA but no detectable helper virus or transforming virus activity. This technique for immortalization of primary human cells without alteration of the differentiated characteristics of the cell type is readily applied to a variety of human cell types. Moreover, the ability to separate the immortalizing and transforming activities of viral oncogenes should provide further understanding as to mechanisms of oncogene action.

Biomechanical Phenomena↗
PubMed1985

Synovial sarcoma: an immunohistochemical study.

The immunohistochemical staining pattern of 18 cases of synovial sarcoma with two epithelial-specific monoclonal antibodies is described. This is compared with normal synovium, cases of giant cell tumour of tendon sheath (benign synovioma) and a variety of spindle celled sarcomas. Sixteen cases of synovial sarcoma showed staining of the epithelial component with at least one antibody. No staining was seen in normal synovium or in giant cell tumours of tendon sheath. A small number of malignant schwannomas contained groups of cells which stained positively whilst other spindle cell sarcomas either did not stain or showed 'cross-reaction' type staining only. These results add weight to the proposition that synovial sarcomas do not arise from normal synovium, despite their morphological similarities, but from mesenchymal connective tissue. It is also shown that immunohistochemical staining with anti-epithelial antibodies will emphasize the biphasic pattern of synovial sarcomas allowing their distinction from other sarcomas.

Antibodies, Monoclonal↗
PubMed2005

Ifosfamide, carboplatin, and etoposide (ICE) reinduction chemotherapy in a large cohort of children and adolescents with recurrent/refractory sarcoma: the Children's Cancer Group (CCG) experience.

BACKGROUND: The prognosis for children with recurrent/refractory sarcomas is poor. We determined the overall response rate (ORR) and overall survival (OS) of children with recurrent/refractory sarcomas who were given ifosfamide, carboplatin, and etoposide (ICE) in three Children's Cancer Group (CCG) phase I/II trials. PROCEDURE: Children with recurrent/refractory sarcoma were treated with ifosfamide (1,800 mg/m2/day on day 0-4), carboplatin (400 mg/m2/day on day 0-1), etoposide (100 mg/m2/day on day 0-4) and either rhG-CSF (10 microg/kg/day vs. 5 microg/kg/day, CCG-0894, 71 patients), PIXY321 (500-1,000 microg/m2/day, CCG-0924, 14 patients), or rhG-CSF (5 microg/kg/day) and IL-6 (2.5-5 microg/kg/day, CCG-0931, 12 patients). RESULTS: Ninety-seven patients were evaluable for tumor response, 56 male and 41 female, median age 14.1 years (range 2.8-22.5 years). Tumor types were osteosarcoma (OTS) (n = 34), rhabdomyosarcoma (n = 27), Ewing sarcoma (EWS) (n = 21), soft tissue sarcoma-not otherwise specified (n = 5), undifferentiated sarcoma (n = 6), fibrosarcoma (n = 2), peripheral primitive neuroectodermal tumor (n = 1), and extraosseous Ewing (n = 1). The ORR was 51% (27% complete response [CR]). OS at 1 and 2 years was 49% and 28%, respectively. Patients with CR or partial response (PR) had significantly increased 1- and 2-year OS, 71% and 41%, respectively, (P < 0.001). Rhabdomyosarcoma patients with embryonal histology had significant improvement in 1- and 2-year OS: 82% and 46%, respectively, compared with other histologies, (P < 0.005). CONCLUSIONS: The ORR to ICE reinduction chemotherapy in children with recurrent/refractory sarcoma was 51%. OS of 1 and 2 years appeared significantly improved in patients who had CR or PR following ICE reinduction therapy or who had rhabdomyosarcoma with embryonal histology.

Adolescent↗
PubMed2007

Assessing functional mobility in survivors of lower-extremity sarcoma: reliability and validity of a new assessment tool.

BACKGROUND: Reliability and validity of a new tool, Functional Mobility Assessment (FMA), were examined in patients with lower-extremity sarcoma. FMA requires the patients to physically perform the functional mobility measures, unlike patient self-report or clinician administered measures. PROCEDURE: A sample of 114 subjects participated, 20 healthy volunteers and 94 patients with lower-extremity sarcoma after amputation, limb-sparing, or rotationplasty surgery. Reliability of the FMA was examined by three raters testing 20 healthy volunteers and 23 subjects with lower-extremity sarcoma. Concurrent validity was examined using data from 94 subjects with lower-extremity sarcoma who completed the FMA, Musculoskeletal Tumor Society (MSTS), Short-Form 36 (SF-36v2), and Toronto Extremity Salvage Scale (TESS) scores. Construct validity was measured by the ability of the FMA to discriminate between subjects with and without functional mobility deficits. RESULTS: FMA demonstrated excellent reliability (ICC [2,1] >or=0.97). Moderate correlations were found between FMA and SF-36v2 (r = 0.60, P < 0.01), FMA and MSTS (r = 0.68, P < 0.01), and FMA and TESS (r = 0.62, P < 0.01). The patients with lower-extremity sarcoma scored lower on the FMA as compared to healthy controls (P < 0.01). CONCLUSION: The FMA is a reliable and valid functional outcome measure for patients with lower-extremity sarcoma. This study supports the ability of the FMA to discriminate between patients with varying functional abilities and supports the need to include measures of objective functional mobility in examination of patients with lower-extremity sarcoma.

Amputation, Surgical↗
PubMed2004

Physiotherapy management of patients with HIV-associated Kaposi's sarcoma.

BACKGROUND: Kaposi's sarcoma is the most common form of cancer in patients with human immunodeficiency virus (HIV) infection. Although Kaposi sarcoma lesions may contribute to significant physical impairments, there is a lack of scientific literature detailing the role of physiotherapy in the treatment of HIV-associated Kaposi's sarcoma. The present Case Report includes two males, aged 36 and 39 years, seropositive for HIV with invasive Kaposi's sarcoma. METHOD AND RESULTS: Patient A was evaluated for bilateral foot pain caused by plantar surface Kaposi s sarcoma lesions that rendered him unable to walk. He progressed to walking 400feet after a treatment regimen of gait training with the use of custom plastazote sandals. Patient B was evaluated for right lower extremity lymphoedema secondary to invasive Kaposi's sarcoma. He experienced an 18% reduction in limb volume, a 38% reduction in pain and a 20 degrees increase in terminal knee flexion after therapeutic exercise and the use of compressive bandaging and garments. CONCLUSIONS: This Case Report suggests that physiotherapy interventions may be valuable in the conservative management of patients with HIV-associated Kaposi s sarcoma.

Adult↗
PubMed1999

Uterine sarcomas: the Curie Institut experience. Prognosis factors and adjuvant treatments.

PURPOSE: With a retrospective study at a single institution, we propose to analyze the prognosis factors and adjuvant treatment for uterine sarcomas. MATERIALS AND METHODS: From 1975 to 1995, 73 uterine sarcomas were treated at the Institut Curie, corresponding to 61 T1, 5 T2, and 8 T4 tumors. Thirteen patients had metastatic disease at the time of diagnosis. The mean age was 58 years. In 71% of patients, the presenting sign was bleeding. This series consisted of 44% leiomyosarcomas (LMS), 19% endometrial stromal sarcomas (ESS), and 31% carcinosarcomas or mixed mesodermal sarcomas (MMS). For the grading classification, we used the classification of the Sarcoma Group of the French Federation of Cancer Centres for soft tissue sarcomas. Of the patients, 66% presented a high-grade tumor. RESULTS: The median overall survival was 42 months, with a 5-year survival of 45%. Histological grade, FIGO stage, histology types, and menopausal status were the four independent factors in multivariate analysis. Eighteen patients relapsed locally (25.7%), with 77% central pelvic sites. Patients with radiotherapy and ESS had better local control in multivariate analysis. Thirty-four patients developed metastases (48.6%), mainly pulmonary (58.8%). Eight patients presented with peritoneal disease. High grades and LMS had the worst survival without metastasis in multivariate analysis. CONCLUSION: This study validated our classification for sarcoma grading and confirmed the finding of worst prognosis for LMS and the importance of radiotherapy in local control.

Adult↗
PubMed2000

Low-grade endometrial stromal sarcoma of the ectocervix after therapy for breast cancer.

OBJECTIVE: Low-grade endometrial stromal sarcoma is an uncommon, indolent uterine sarcoma that can arise in extrauterine locations. The objective of this study was to report on a previously unpublished site of origin for a low-grade endometrial stromal sarcoma. METHODS: A case of a low-grade endometrial stromal sarcoma arising in the ectocervix after goserelin hormonal therapy for breast cancer was studied. RESULTS: Low-grade endometrial stromal sarcoma can arise in the ectocervix even in the absence of endometriosis. CONCLUSION: Low-grade endometrial stromal sarcoma should be included in the differential diagnosis of sarcomas of the ectocervix.

Antineoplastic Agents, Hormonal↗
PubMed2002

Vulvar epithelioid sarcoma in pregnancy.

BACKGROUND: Epithelioid sarcoma is a soft tissue tumor rarely found centrally and even less commonly on the vulva. Vulvar sarcoma in pregnancy is also exceedingly rare with only five cases reported to date, none of which have been an epithelioid sarcoma. CASE: We report a case of a 29-year-old woman presenting with a vulvar epithelioid sarcoma at 36 weeks of gestation. The patient underwent a radical resection 6 weeks postpartum followed by chemotherapy. Despite a radical hemivulvectomy and doxorubicin and ifosfamide chemotherapy, she developed pulmonary metastasis and died of tumor-related pulmonary failure secondary to her disease 612 months after diagnosis. To our knowledge this is the first case of a vulvar epithelioid sarcoma presenting during pregnancy. The English literature is reviewed and a total of 18 previous cases of vulvar epithelioid sarcoma have been reported outside of pregnancy. Insight into the biological behavior and therapeutic management of this disease is discussed. CONCLUSION: The optimal management of vulvar epithelioid sarcoma remains to be determined. However, it would seem that early and aggressive surgical resection provides the best possibility for cure. The role of radiation and/or chemotherapy remains to be determined.

Adult↗
PubMed2006

Targeted therapies in Ewing's sarcoma.

Ewing's sarcoma, the second most common malignant bone tumor, is an extremely aggressive neoplasm, mainly occurring in children and adolescents. Ewing's sarcoma shows a low survival rate despite the adoption of multimodal treatments, including local control of the disease by surgery and/or radiotherapy and multidrug adjuvant chemotherapy. No new effective drugs have been recently described and proposed for sarcomas and, therefore, innovative treatment modalities are very welcome and needed. In this respect, two new entry sites for therapeutic intervention may derive from tailored therapies against the insulin-like growth factor receptor I (IGF-IR) or CD99, a cell surface transmembrane protein highly expressed in Ewing's sarcoma. Neutralizing IGF-IR functions was shown to significantly affect Ewing's sarcoma malignancy. However, it is only recently that new clinically applicable drugs targeting IGF-IR are available and represent a concrete opportunity. Engagement of CD99 induces massive apoptosis of Ewing's sarcoma cells through caspase-independent mechanisms and reduces their malignant potential. Since the apoptotic functions of this molecule are of potential clinical interest, the effects of a tailored therapy triggering CD99 were analyzed against Ewing's sarcoma local tumors and distal (lung and bone) metastases in athymic mice. The effects of targeted therapies against CD99 or IGF-IR were evaluated in combination with conventional chemotherapeutic agents to assess best drug-drug interactions and treatment schedule. Toxic effects of these tailored therapies were also considered to offer the necessary rationale for the application of possible forthcoming clinical trials.

12E7 Antigen↗
PubMed1983

Scanning and transmission electron microscopy of Ewing's sarcoma of bone (typical and atypical variants). An analysis of nine cases.

Scanning electron microscopy (SEM) is of value for the differential diagnosis of Ewing's tumor of bone. Based upon 9 new cases which were observed with SEM and TEM (transmission electron microscopy), this paper puts into consideration, for the first time, the SEM ultrastructure of Ewing's sarcoma (both variants; typical Ewing's sarcoma and the large cell Ewing's sarcoma). Furthermore, a new case of vascular Ewing's sarcoma, studied with TEM, is discussed and included in the differential diagnosis with other round cell sarcomas of bone. Both Ewing's sarcoma types evidence common ultrastructural characteristics, but the atypical variant (large cell type) shows a greater variation in cell size and contour. The cell surfaces displayed smooth structures, interrupted only by clusters of short, stub-like microvilli. Isolated cilia were also observed. Variations in cell contour and size within the same tumour are also induced through intensive chemotherapy, as noted in one of our cases. SEM seems to be suitable for the differentiation of Ewing's tumours from other primary malignancies of the bone marrow, as is the case of the so-called "reticulum cell sarcoma of bone" or malignant non-Hodgkin lymphoma. SEM studies associated with TEM give further support to the mesenchymal origin of this neoplasm.

Adolescent↗
PubMedDate not supplied

Contributions from surgeons to clinical trials and research on the management of soft tissue sarcoma.

BACKGROUND: Surgical resection is the primary treatment for soft tissue sarcoma. Surgeons are in a position to develop and define appropriate treatment strategies for this disease. In an effort to define the contributions of surgeons to the management of sarcoma, the surgical and clinical oncology literature from January 1983 through June 1996 was reviewed. METHODS: A computerized literature search of the Cancerlit database for January 1983 to June 1996 was performed. The search was limited to the topic of soft tissue sarcoma and was further confined to 15 journals that publish articles relevant to surgical management. These studies were then categorized by multiple parameters and analyzed. RESULTS: The Cancerlit file contained 4478 articles in which sarcoma was the primary topic. When the search was limited to 15 journals frequently read by surgeons, 479 references (11%) were retrieved. Within the surgical literature, 95 of the 479 articles (20%) described prospective studies, of which 33 were prospective and randomized. These studies represent all but three of the prospective randomized trials within the literature during the time period reviewed. The management of patients with sarcoma was evaluated in 26 of the prospective randomized trials; of these, 13 trials evaluated adjuvant chemotherapy, three evaluated adjuvant radiotherapy, and ten evaluated the chemotherapeutic treatment of metastatic disease. Surgical oncologists were the first or senior author on 10 of the 16 prospective randomized studies regarding adjuvant radiation or chemotherapy. Four of the 16 trials evaluating adjuvant therapy contained more than 100 patients, and three of those four were from cooperative group efforts. All but one of the studies of adjuvant therapy with less than 100 patients were from single institutional trials. CONCLUSIONS: Although the surgical and clinical oncology literature on soft tissue sarcoma is composed primarily of retrospective reviews, the prospective randomized trials reported represent almost all of the randomized trials in the literature and have significant contributions from surgeons. Surgeons can guide and design clinical trials, but overall patient accrual as represented by soft tissue sarcoma is low, and may be improved through cooperative group efforts.

General Surgery↗