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PubMed1999

Synovial sarcoma specific translocation associated with both epithelial and spindle cell components.

The biphasic subtype of synovial sarcoma consists of both epithelial and spindle cell components. To address the relationship between the different cellular components found in synovial sarcoma, we deduced the presence of the synovial sarcoma-specific der(X)t(X;18)(p11.2;q11.2), and involvement of the SSX1 gene in both the epithelial/glandular and spindle cell components of 3 biphasic synovial sarcomas with wide ranging proportions of each of the 2 elements. This has been achieved using a 2-color fluorescence in situ hybridization (FISH) methodology that we had developed recently for analysis paraffin-embedded material. The presence of the rearrangement could be deduced in histologically defined regions and the results showed clearly that the rearrangement was present in both cellular components. This finding provides direct genetic evidence for biphasic synovial sarcomas being clonal and truly biphasic.

Adult↗

PubMed1996

Cytogenetic studies on fine-needle aspiration samples from osteosarcoma and Ewing's sarcoma.

The preoperative multidrug chemotherapy of osteosarcoma and Ewing's sarcoma patients requires a reliable diagnosis. There are several advantages with obtaining the diagnosis by fine-needle aspiration (FNA) and cytologic examination. Although cytologic criteria have been defined, adjunctive methods such as cytogenetic analysis are valuable to support the diagnosis. We have cytogenetically analyzed FNAs from 18 primary bone sarcomas (six osteosarcomas and 12 Ewing's sarcomas). Two of the osteosarcomas showed abnormal, complex karyotypes seen in most highly-malignant osteosarcomas. Seven Ewing's sarcoma aspirates displayed abnormal karyotypes; five of these had the characteristic 11;22 translocation, and in one of these cases molecular genetic analysis revealed the hybrid EWS/FLI1 transcript. Since only two of six osteosarcomas showed clonal changes, chromosomal analysis of FNAs from suspected osteosarcoma seems to be of limited value, but may in some cases support the diagnosis of high-grade malignancy. In Ewing's sarcomas, however, the finding of an 11;22 translocation was valuable and strongly supported the cytologic diagnosis. As shown in one case, the material obtained by FNA is sufficient for cytologic, cytogenetic, and molecular genetic analysis.

Adolescent↗

PubMedDate not supplied

Optimal radiologic imaging of soft tissue sarcomas.

Radiologic evaluation of the patient with soft tissue sarcoma may include conventional radiography, scintigraphy, ultrasonography (US), computed tomography (CT), and magnetic resonance (MR) imaging. The radiologist also plays a critical role in the evaluation of the patient with soft tissue sarcoma by guiding and performing aspiration biopsies. This review discusses the use of radiological techniques to evaluate the primary lesion and to detect recurrences. In adults, soft tissue sarcoma most commonly occurs in the extremities, and this review emphasizes the role of MR imaging in the pre- and post-treatment evaluation of extremity soft tissue sarcomas. The role of imaging studies in the evaluation of soft tissue sarcomas in the abdomen, thorax, and the head and neck region is also discussed.

Biopsy, Needle↗

PubMed1978

Curability of Ewing's sarcoma and considerations for future therapeutic trials.

Twenty previously untreated children with primary Ewing's sarcoma and 8 children with primary tumor and metastatic disease were treated with surgery or radiation therapy (6,000-7,000 rads) for their primary tumor and T-2 chemotherapy. Of the 20 children with primary Ewing's sarcoma treated with T-2 "adjuvant" chemotherapy, 15 had no evidence of recurrent disease for from 31+-82+ months (median 46+ months) from the start of treatment. The actuarial 5-year disease-free survival rate for this group of patients was 75%. Eight patients presenting with metastatic disease had complete responses to T-2 chemotherapy, but 7/8 with metastatic disease eventually had tumor recurrence. Examination of the treatment failures, both those patients relapsing after adjuvant chemotherapy for primary Ewing's sarcoma (5), and those relapsing after having a complete response of metastatic disease (7) to T-2 chemotherapy, revealed that all relapses occurred at the end of the second year of T-2 chemotherapy or after chemotherapy was stopped. In addition, of 23 patients receiving "curative" radiation therapy to their primary tumor, 5 had local recurrence (22%) and 6 (26%) had severe functional debility secondary to combined radiation therapy and T-2 chemotherapy. The conclusions drawn from this experience have led us to consider a new approach to the treatment of Ewing's sarcoma, namely: 1) more aggressive initial or "induction" chemotherapy with subsequent T-2 "maintenance" chemotherapy to eradicate more completely all metastatic microfoci of disease presumed to be present in patients with primary tumor at the time of diagnosis, and ostensively present in patients with metastatic disease; 2) the use of surgery alone or in combination with moderate doses of radiation therapy in those patients in whom we can predict a high frequency of local recurrence (pelvic lesions) or a high percentage of "functional failures" (young children with lower extremity lesions). Preliminary results with this latter approach are encouraging with 11/13 patients with primary Ewing's sarcoma free of disease at 12+-26+ months. A longer follow-up of this more aggressive treatment is needed to determine the superiority of this approach for both increased survival and improved late physical rehabilitation.

Child↗

PubMed1978

The role of radiation therapy in the treatment of soft tissue sarcomas of childhood.

The treatment of soft tissue sarcomas in children at the Joint Center for Radiation Therapy, Children's Hospital Medical Center, and the Sidney Farber Cancer Institute from 1970 to 1976 has been reviewed. Twenty-seven patients were diagnosed with rhabdomyosarcoma, and twenty patients were diagnosed with soft tissue sarcomas of other histologies. An aggressive, combined modality therapeutic approach was applied in the treatment of all patients with emphasis placed on conservation of function. Of irradiated patients, local control was achieved in 96% of those with rhabdomyosarcoma and 85% in other sarcomas. Cumulative relapse-free survival (actuarial) at 5 years is projected at 65% for the rhabdomyosarcoma patients and at 63% for the other sarcoma patients. Although there were differences in chemotherapy regimens (vincristine, actinomycin-D and cyclophosphamide for rhabdomyosarcoma and adriamycin and DTIC for other soft tissue sarcomas), the surgical and radiation therapeutic approaches are similar for both groups. The high probability of local control using function-conserving surgery and high dose radiation therapy supports this emerging approach. Improvements in survival will require better control of metastatic disease.

Adolescent↗

PubMed1980

In vivo utilization of substrate by human sarcoma-bearing limbs.

Human sarcoma-bearing limb substrate utilization was characterized by studying 10 otherwise healthy patients with extremity sarcomas (five osteosarcomas, five soft tissue sarcomas). All patients were studied in the postabsorptive state. Extremity blood flow was measured using a non-invasive capacitance plethysmograph. Percutaneous arterial and venous effluent blood samples from the tumor-bearing (TB) and control extremity were obtained and flux was calculated for free fatty acids (FFA), glucose, and amino acids. The control limb showed a release of amino acids similar to that reported previously. There was a dramatic difference in the TB extremity, which consistently released fewer amino acids. Both the TB and control limbs released FFA at the same rate. A significant difference in glucose uptake between TB and control limbs was noted for soft tissue sarcoma patients but not osteogenic sarcoma patients. The amount extracted correlated with excised tumor size and gluconeogenic amino acid release from the contralateral normal limb. This study suggests that the tumor-bearing limb ignores the inherent conservation mechanisms in the postabsorptive state and continues to utilize substrate, apparently at the expense of host tissues.

Adolescent↗

PubMed1984

Sarcoma of bone and soft tissue following treatment of Hodgkin's disease.

Intensive chemotherapy and radiotherapy of Hodgkin's Disease has resulted in improved survival rates. With long-term follow-up, however, a risk of secondary malignancy in these individuals is now appreciated. The authors of this report have encountered five patients who developed bone or soft tissue sarcomata more than 5 years after treatment of Hodgkin's Disease. The four males and one female ranged in age from 14 to 74 years at the time of diagnosis of Hodgkin's disease. Two had received radiotherapy alone for treatment of Hodgkin's disease, two were treated with radiation and chemotherapy, and one received only chemotherapy. The latent period prior to diagnosis of sarcoma ranged from 6 to 11 years. There was one case each of neurofibrosarcoma, fibrosarcoma, osteosarcoma, liposarcoma and leiomyosarcoma. Four patients died within 1 year of the diagnosis of sarcoma. One is alive with no evidence of disease 2 years following diagnosis and surgical excision of the sarcoma. On the basis of the Massachusetts General Hospital experience in the treatment of Hodgkin's Disease, the authors calculate a risk of 0.9% of sarcoma occurring in five year survivors of Hodgkin's disease. Previously reported cases of sarcoma following treatment of Hodgkin's disease are summarized. The pertinent literature is reviewed.

Adult↗

PubMed1984

Tumor-cell heterogeneity in soft tissue sarcomas as defined by chemoradiotherapy.

This report documents heterogeneous cell populations within high-grade soft tissue sarcomas in seven patients. The authors observed that, following chemoradiotherapy (five patients) or chemotherapy alone (two patients), surgically resected residual or recurrent sarcoma was found to be of low-grade histology. All chemotherapy was of Adriamycin (doxorubicin)-containing combinations. Seven other patients with regional recurrence after resection of high-grade sarcomas had high-grade recurrent tumors. Five of these patients had received no adjuvant therapy; two with extensive retroperitoneal liposarcomas and gross tumor-involved margins had received chemoradiotherapy. Follow-up ranged from 3 to 60 months (median, 12 months). These findings suggest that high-grade populations of sarcoma cells are more susceptible to chemoradiotherapy, as long as there is minimal residual disease. Low-grade clones of tumor cells may survive such therapy and present as clinical recurrence after initial treatment of low-grade or high-grade soft tissue sarcomas. Surgical resection is warranted for these recurrent lesions.

Adult↗

PubMed1987

Clinical experience with intravenous radiosensitizers in unresectable sarcomas.

Traditionally, adult bone and soft tissue sarcomas have been considered to be "radioresistant." Because of this philosophy, patients who present with locally advanced, unresectable sarcomas often are treated in a palliative fashion, usually with low-dose radiotherapy. Over the last 6 years, 29 patients with unresectable primary or metastatic sarcomas were treated using a combination of intravenous chemical radiosensitizers and high-dose irradiation. Twenty-two of 29 patients achieved clinical local control, with six patients having a complete clinical response. The time to tumor response is often several months or longer, which is in contrast to other tumor histologies (carcinomas, lymphomas), where tumor response usually occurs over several weeks. Several large tumors have shown only a minimal tumor response, yet were found to be sterilized in posttreatment biopsy or autopsy examination. Of 15 patients with primary sarcomas without metastases, 11 patients (73%) remain free of local tumor progression from 12 to 83 months. Adult high-grade sarcomas can be controlled with high-dose radiotherapy and intravenous radiosensitizers, although the precise role of these agents is unclear.

Adolescent↗

PubMed1988

Sarcoma metastatic to the brain.

Five patients with nonlymphomatous sarcoma metastatic to the brain are presented and the literature reviewed. In 50 patients, brain metastasis was verified pathologically and some case data were available, including the five reported here. In five patients, there was pathologic verification but no case data. Thirty-nine other patients were found without such verification. Reportedly, most types of sarcomas are able to metastasize to the brain, and are represented in these 94 patients. Fibrosarcoma and alveolar soft-part sarcoma tumors metastasize to the brain without regard to treatment technique. There may be a group of tumors, including malignant fibrous histiocytoma, rhabdomyosarcoma, and perhaps leiomyosarcoma and osteosarcoma, in which the incidence of brain metastases has increased with improved sarcoma chemotherapy (CT). In this group particularly, but also in alveolar soft-part sarcoma and others, the presence of lung metastases may increase the probability of brain metastasis occurring subsequently.

Adolescent↗

PubMed1988

Translocation t(X;18) in orofacial synovial sarcoma.

Cytogenetic analysis of a synovial sarcoma of the base of the tongue showed a reciprocal translocation involving chromosomes X and 18 [t(X;18)(p11.2;q11.2)]. This is a translocation recently reported to be characteristic of synovial sarcomas of the extremities. The histogenesis of synovial sarcoma is controversial. Our discovery of this translocation in an oral synovial sarcoma confirms the unity of origin of this neoplasm with the far more common synovial sarcomas of the extremity. Karyotypic analysis may prove useful in confirming the diagnosis of this uncommon neoplasm.

Adult↗

PubMed1988

Disease patterns and survival rate in children with metastatic soft-tissue sarcoma. A report from the Intergroup Rhabdomyosarcoma Study (IRS)-I.

The patterns of disease extent, response to treatment, and survival rates were examined in 129 children registered as metastatic (Group IV) soft-tissue sarcoma patients on the Intergroup Rhabdomyosarcoma Study (IRS)-I protocol from November 1972 through October 1978. The patients' ages at diagnosis ranged from 3 months to 21 years (median, 10.5 years); 72 were male patients and 57 were female patients (male-to-female ratio, 1.3:1). The tumor arose in an extremity in 34 patients, the head and neck (exclusive of the orbit) in 27, the genitourinary tract in 25, the retroperitoneum or pelvis in 14, the trunk in 12, the intrathoracic region in nine, the hepatobiliary system in four, the perineum in two, and the orbit in two patients. The histologic types of soft-tissue sarcoma confirmed by the pathology review committee were embryonal rhabdomyosarcoma in 68 patients, alveolar rhabdomyosarcoma in 41, undifferentiated sarcoma in 14, embryonal-botryoid in two, pleomorphic in one patient, and other sarcoma in three patients. Of 105 patients who were confirmed in Group IV and had complete information concerning sites of metastatic deposits, 53 patients presented with metastases restricted to only one anatomic region or tissue; the other 52 had diffuse metastases. The most common sites of distant tumor deposits were the lungs, bone marrow, and other soft tissues. After treatment with vincristine, dactinomycin, and cyclophosphamide with or without Adriamycin (Adria Laboratories, Inc., Columbus, OH) and radiation therapy, 65 (50%) of the 129 eligible patients achieved complete disappearance of all detectable tumor. The likelihood of achieving and maintaining a complete response for 2 years was highest among patients whose tumors originated in the genitourinary tract, retroperitoneum-pelvis, or the hepatobiliary or perineum regions. Thirteen of these 45 children (29%) are alive and disease-free at a minimum of 2 years after initiation of treatment. Only 10 of the other 84 (8%) are surviving disease-free at 2 years (P = 0.02). The presence of restricted rather than diffuse metastases at diagnosis (P = 0.02) was the only other characteristic significantly related to long-term complete remissions. One hundred and two patients (79%) died at a median of 47 weeks after diagnosis, 92 from sarcoma and ten from other causes.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1989

A case-control study of risk factors for sarcomas of the uterus. The World Health Organization Collaborative Study of Neoplasia and Steroid Contraceptives.

Using data collected as part of the hospital-based World Health Organization (WHO) Collaborative Study of Neoplasia and Steroid Contraceptives, the authors examined potential risk factors for sarcoma of the uterus. Twenty-nine patients with uterine sarcoma who were between 15 and 56 years of age and diagnosed at one of nine centers were matched on age and center to 198 controls selected from hospital admissions to other than obstetric and gynecologic wards. All women were interviewed regarding their medical and reproductive history, methods of birth control, and history of sexual relationships and of sexually transmitted infections. The risk of uterine sarcoma was lower in parous women compared to nulliparous women (odds ratio [OR] = 0.6; 95% confidence interval [CI] = 0.1, 3.3), and the risk decreased with increasing number of live births. A greater proportion of cases than controls reported giving birth to their first child at the age of 25 or later, even after adjustment for parity (OR = 3.5; 95% CI = 1.2, 10.9). Cases were also more likely than controls to report a history of a spontaneous abortion (OR = 2.5; 95% CI = 0.8, 7.4) or an induced abortion (OR = 1.6; 95% CI = 0.4, 6.3). Late menarche and early menopause were both positively associated with the risk of uterine sarcoma. No association was observed with a history of infertility, use of oral contraceptives, or measures of sexual activity. The findings with respect to childbearing and menstrual history differ from those of a recent cohort study, and indicate the need for larger investigations to assess the role of these and other risk factors in the occurrence of sarcomas of the uterus.

Abortion, Spontaneous↗

PubMed1991

Limb salvage surgery for bone and soft tissue sarcoma. A phase II pathologic study of preoperative intraarterial cisplatin.

Preoperative therapy has been tested as part of limb salvage therapy for localized bone and soft tissue sarcoma of the extremities. The activity of cisplatin (CDDP) by intraarterial (IA) infusion was evaluated in 40 cases of which 36 were evaluable for response. All patients had high-grade sarcomas. All but 3 patients received 3 or 4 courses (24 patients received 4 courses) of CDDP at a dosage of 120 to 150 mg/m2 given over 6 hours every 2 weeks by IA infusion. Patients younger than 18 years of age received the higher dose of CDDP. Treatment was well tolerated with combination antiemetics. One patient experienced severe hearing loss with the first cycle of the higher CDDP dose. Pathologic evaluation of resected osteosarcoma showed a favorable response (90% or greater necrosis) in 8 of 20 evaluable cases and in 3 of 4 patients with malignant fibrous histiocytoma (MFH) of bone (without osteoid). In soft tissue sarcomas, minimal (50% to 89%) necrosis was seen in two of nine cases and none had 90% or greater necrosis. Patients received postoperative chemotherapy based on pathologic response, but the value of this postoperative adjuvant therapy requires further follow-up and is uncertain in this small study. IA CDDP can often cause significant tumor necrosis in patients with bone sarcomas, whereas soft tissue sarcomas are less sensitive to this therapy.

Adolescent↗

PubMed1993

Cytogenetic profile of uterine sarcomas.

BACKGROUND: Diagnostic and consistent chromosomal abnormalities have been reported in several soft tissue sarcomas, but few studies have reported the frequency of chromosomal abnormalities in uterine sarcomas. METHODS: Cytogenetic studies were performed on specimens of uterine sarcoma from 14 patients. The specimens included five of leiomyosarcoma (LMS), four of endometrial stroma sarcoma (ESS), and five of malignant mixed mesodermal tumor (MMMT). RESULTS: Chromosomal abnormalities were detected in 10 of 14 (71%) patients. Chromosome 1 was involved in 7 of 13 (54%) of the patients, chromosome 11 in 6 of 13 (46%), and chromosome 7 in 6 of 13 (46%). A site-specific chromosomal abnormality, del(11)(q22) was found in two patients with LMS and three patients with MMMT, and 7q31 also was involved frequently. Marked genomic instability characterized the MMMT studied. CONCLUSIONS: These findings suggest that abnormalities of chromosomes 1, 7, and 11 may play a role in tumor initiation or progression in uterine sarcomas. Genomic alterations in the region 11q22 may be specific for malignant smooth muscle tumors of the uterus.

Adult↗

PubMed1993

Synovial sarcoma of childhood and adolescence. Report of the German CWS-81 study.

BACKGROUND: Synovial sarcoma is the third most common pediatric soft tissue tumor. It requires an aggressive approach to achieve a cure. However, optimal treatment modalities adapted to disease extension and histologic variants have not been determined because there is little information about prospectively treated patients. METHODS: A multicenter trial for soft tissue sarcomas (Protocol CWS 81) was conducted in West Germany between 1981-1985, and 31 patients with synovial sarcoma were registered. Treatment included multiagent chemotherapy and irradiation after initial tumor excision or biopsy. The male-female ratio in this group was 1:1.6 with a median age of 14 years (range, 1-19 years). The median follow-up time after diagnosis was 101 months (range, 77-131 months). RESULTS: The overall event-free survival (EFS) for patients with synovial sarcoma was 74.2% at 5 years. Group I-II tumors had a significantly better prognosis than those in Group III-IV (EFS at 5 years 84.4% and 58.3%, respectively; P = 0.024). Small tumors (< 5 cm) responded better than larger tumors (> or = 5 cm; EFS, 93% versus 58%; P = 0.029). Synovial sarcoma involved the extremities in 28 patients who had a better outcome compared with those with extremity rhabdomyosarcoma in this study (EFS for Group I-IV was 82% versus 24%, P = 0.001). CONCLUSIONS: The results appeared superior to previous experience using radical surgery alone and suggested that after initial, nonmutilating surgery, adjuvant chemotherapy, and irradiation contributed to the improved long-term survival.

Adolescent↗

PubMed1993

Edatrexate in patients with soft tissue sarcoma. Activity in malignant fibrous histiocytoma.

BACKGROUND: Chemotherapy has had little impact on the natural history of soft tissue sarcoma, and often is associated with serious toxicity. Edatrexate, an investigational antifolate, is active in patients with lung cancer, and has cytotoxic activity in human sarcoma cell lines. METHODS: Edatrexate was administered to 36 patients with measurable, advanced soft tissue sarcoma who had not previously received chemotherapy. The drug was given weekly for 5 weeks, then every other week. The initial dose, 80 mg/m2, was escalated by 10 mg/m2 every 2 weeks in the absence of toxicity. Eleven patients had leiomyosarcoma, 7 had malignant fibrous histiocytoma (MFH), and 5 had liposarcoma; the remainder of cell types included hemangiopericytoma (4), angiosarcoma (3), synovial (2), spindle cell (2), extraosseous chondrosarcoma (1), and fibrosarcoma (1). RESULTS: Thirty-five patients are evaluable. Partial response (PR) was seen in five of the seven patients with MFH; no other major responses occurred. Overall, the response frequency was 14% (two-sided 95% confidence interval, 3% to 26%). Median duration of PR was 6 months (range, 4-18 months). One patient had a minor tumor regression, and six had stable disease. Myelosuppression was generally mild; only three patients had grade 3 hematologic toxicity. Modification of dose or schedule was required in 50% of patients for mucositis. Fatigue was a common toxicity, seen in 66% of patients, but was tolerable in the majority. A rash was seen in 46% of patients; one patient had hepatic toxicity. CONCLUSIONS: Overall, the activity of edatrexate in this study, dominated by patients with either visceral or vascular sarcoma, was poor. However, the responses observed in patients with metastatic MFH suggests that further evaluation of edatrexate in patients with soft tissue sarcoma is warranted.

Adult↗

PubMed1993

Postirradiation sarcoma of the head and neck.

BACKGROUND: With improvement in survival after cancer treatment, it is becoming increasingly important to study treatment-related morbidity and mortality. Sarcoma can develop in the irradiated field after radiation therapy. The authors performed a study to estimate the risk, and compared the risk of sarcoma after radiation therapy with that of other treatment modalities used against cancer. METHODS: Between 1955 and 1988, 229 patients with sarcoma of the head and neck were seen at the University of California, Los Angeles (UCLA), Medical Center. Of these, 13 (6%) had a previous history of radiation therapy to the head and neck. RESULTS: Radiation doses were known in 10 of 13 patients and ranged from 30 to 124.4 Gy. The latency time from radiation therapy to the development of postirradiation sarcoma (PIS) ranged from 3 months to 50 years, with a median of 12 years. More than 2000 patients have received radiation therapy to the head and neck for various conditions at the UCLA Medical Center since 1955. CONCLUSIONS: The authors conclude that most head and neck sarcomas are not radiation related and that the risk of PIS after head and neck irradiation for other diseases is low. From a review of the literature comparing mortality risks of chemotherapy, general surgery, and anesthesia, the risk of PIS appears no worse. Given the large number of patients who can be cured or receive palliation with radiation therapy, concern about PIS should not be a major factor influencing treatment decisions in patients with cancer.

Adolescent↗