Proceedings: Chemotherapy of soft-tissue sarcomas.
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Adolescent↗
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Results for “SARCOMA, LIPOSARCOMA”
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Phase I-II trial of ONYX-015 in combination with MAP chemotherapy in patients with advanced sarcomas.
ONYX-015 is a provisionally replication competent adenovirus with oncolytic activity in cells with malfunctioning p53. Sarcomas represent a rational target for this approach given the high frequency of p53 mutations (40-75%) and MDM-2 amplification (10-30%). We, therefore, undertook a phase I/II study of ONYX-015, days 1-5 every month administered intratumorally under radiographic guidance, in combination with MAP (mitomycin-C, doxorubicin, cisplatin) chemotherapy in patients with advanced sarcoma. Six patients were treated. Injected lesions included liver metastases in four patients and chest wall metastases in two patients. Sarcoma histologies were gastrointestinal stromal tumors (GIST, two patients), leiomyosarcoma (two patients), liposarcoma (one patient), and malignant peripheral nerve sheath tumor (1 patient). Dose escalation was performed from 10(9) plaque forming units (PFU)/dose (total dose of 5 x 10(9) PFU/cycle) to 10(10) PFU/dose (total dose of 5 x 10(10) PFU/cycle) without dose-limiting toxicity being encountered. Immunohistochemistry of the metastatic lesions prior to treatment showed that five out of six patients were positive for p53, while two patients also had mdm-2 overexpression. Adenoviral replication was detected in two out of six patient biopsies on day 5 of the first cycle, by in situ hybridization (ISH). Both patients were treated at the highest dose level. ONYX-015 viral DNA was detected by quantitative PCR in the plasma of 5/6 patients on day 5 of the first cycle, and up to day 12 (7 days after the last viral dose) in one patient who had extended sampling for viral kinetics performed, suggesting viral replication in sarcoma tissue. One patient with p53 mutation and MDM-2 amplification achieved a partial response to treatment that lasted 11 months. In conclusion, intratumoral administration of ONYX-015 in combination with MAP chemotherapy is well tolerated with no significant toxicity due to ONYX-015 being encountered. Detection of viral DNA in post treatment tumor specimens by ISH and detection of the ONYX-015 genome in the peripheral blood by quantitative PCR, up to 7 days after the last viral dose provide evidence for adenoviral replication. There was evidence of antitumor activity in one out of six patients. Further investigation of this approach in patients with recurrent sarcomas is warranted.
Adenoviridae↗
Primary retroperitoneal sarcomas--a report of 16 cases.
From November 1982 to August 1990, 16 patients with primary retroperitoneal sarcoma were treated in our hospital. The most frequent types of tumor were liposarcoma (6), malignant fibrous histiocytoma (3). The commonest clinical findings were palpable abdominal mass (14/16). In management of these patients; nine patients underwent complete resection of the tumor; three patients underwent partial resection of the tumor and four patients underwent biopsy only. The histology of tumor appeared to have prognostic significance. Patients suffering from liposarcoma (3/5) and malignant fibrous histiocytoma (1/2) survived the longest. With a mean follow up of 25.0 months, the three year overall survival rate of complete resection group was 50 per cent. No patients with partial resection and biopsy only group survive three years and the total three-years overall survival rate was 29%. The mean survival for patients after adjuvant chemotherapy and/or radiotherapy was similar to that after a radical operation alone. The prognosis of primary retroperitoneal sarcoma is grave and complete resection of the tumor as initial treatment seems to provide the only chance of cure for these patients.
Adolescent↗
Myofibroblasts in soft tissue sarcomas.
A series of 129 soft tissue sarcomas was examined ultrastructurally to determine in which neoplasms and to what extent myofibroblasts could be demonstrated. Twenty cases of fibromatosis and fasciitis served as controls. Myofibroblasts were identified in all 30 cases of malignant fibrous histiocytoma and all 4 cases of well-differentiated sclerosing liposarcoma. Though most numerous in areas of desmoplasia, in no instance did myofibroblasts constitute the dominant cellular constituent of either neoplasm. Myofibroblasts were identified with lesser frequency and in smaller numbers in fibrosarcoma, synovial sarcoma, malignant hemangiopericytoma and neuroblastoma. None were observed in a wide assortment of diverse sarcomas in which desmoplasia was not a feature. In comparison each lesion judged by light microscopy to represent either fibromatosis or fasciitis was composed principally of myofibroblasts. The demonstration of abundant myofibroblasts within a soft tissue lesion which has been subjected to wide sampling strongly suggests a benign proliferative process as opposed to a malignant neoplasm. It is hypothesized that myofibroblasts observed within collagenized regions of soft tissue sarcomas may constitute an expression of host response to neoplasia.
Fibroblasts↗
[Soft tissue sarcoma of the limbs].
24 cases of soft tissue tumors treated during the last 10 years are analysed. Therapeutical results and a review of the literature are presented. Survival of patients with these types of tumors is very limited. Two points have to be emphasized. --Exact histological diagnosis, large surgical resection at distance of the neoplasm, done by an experienced surgeon give the best chances of good results. In many cases this means heavy surgery and severe functional loss. --The future will surely bring better treatment for these still poorly known tumors. Perfect knowledge of the topography of the neoplasm is necessary to perform surgery in best conditions. Chemotherapy and radiotherapy should be tested on larger series of cases to prove their efficiency.
Adult↗
[Cytogenetic data on sarcomas of the bone and soft tissue].
Cytogenetic data are now available in most bone and soft tissue sarcomas. The characteristic chromosomal rearrangements observed are of great importance for the diagnosis, the classification and the comprehension of these cancers at the molecular level.
Bone Neoplasms↗
Mcl-1 is a novel therapeutic target for human sarcoma: synergistic inhibition of human sarcoma xenotransplants by a combination of mcl-1 antisense oligonucleotides with low-dose cyclophosphamide.
PURPOSE: Little is known about the role that Mcl-1, an antiapoptotic Bcl-2 family member, plays in solid tumor biology and susceptibility to anticancer therapy. We observed that the Mcl-1 protein is widely expressed in human sarcoma cell lines of different histological origin (n = 7). Because the expression of antiapoptotic Bcl-2 family proteins can significantly contribute to the chemoresistance of human malignancies, we used an antisense strategy to address this issue in sarcoma. EXPERIMENTAL DESIGN: SCID mice (n = 6/group) received s.c. injections of SW872 liposarcoma cells. After development of palpable tumors, mice were treated by s.c.-implanted miniosmotic pumps prefilled with saline or antisense or universal control oligonucleotides (20 mg/kg/day for 2 weeks). On days 2, 6, and 10, mice were treated with low-dose cyclophosphamide (35 mg/kg i.p) or saline control. During the experiments, tumor weight was assessed twice weekly by caliper measurements. On day 14, animals were sacrificed. Tumors were weighed and fixed in formalin for immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling analysis. RESULTS: Mcl-1 antisense oligonucleotides specifically reduced Mcl-1 protein expression but produced no reduction in tumor weight compared with saline-treated control animals. Cyclophosphamide monotreatment caused only modest tumor weight reduction compared with saline control. However, use of Mcl-1 antisense oligonucleotides combined with cyclophosphamide clearly enhanced tumor cell apoptosis and significantly reduced tumor weight by more than two-thirds compared with respective control treatments. CONCLUSION: A combination of Mcl-1 antisense oligonucleotides with low-dose cyclophosphamide provides a synergistic antitumor effect and might qualify as a promising strategy to overcome chemoresistance in human sarcoma.
Animals↗
Calretinin expression in tumors of adipose tissue.
Although well established as a marker of mesothelial cells, calretinin is also expressed in several other tissue types, including adipose tissue. Accordingly, immunohistochemical staining for calretinin has been described in an increasing number of neoplasms other than mesothelioma. A detailed analysis of calretinin expression in lipogenic tumors has not yet been reported, however. Given the known expression patterns of calretinin in normal tissues, we predicted that calretinin immunoreactivity would be detected in lipoma and the various histologic subtypes of liposarcoma, and that this marker might be of use in the differential diagnosis of selected fatty tumors. A variety of pleomorphic and small round cell sarcomas were studied for comparison. Calretinin immunoreactivity was detected, at least focally, in all 10 samples of normal adipose tissue and in 22 of 23 lipomas or lipoma variants. Staining for calretinin was also positive within the lipogenic component of 28 of 29 liposarcoma variants. Of the 7 dedifferentiated liposarcomas, 3 were focally positive for calretinin. Pleomorphic variants of other sarcomas, including undifferentiated high-grade pleomorphic sarcoma, rhabdomyosarcoma, leiomyosarcoma, and malignant peripheral nerve sheath tumor also exhibited focal calretinin immunoreactivity in a minority of cases, as did some small round cell sarcomas. These results suggest that calretinin immunoreactivity in normal and neoplastic adipose tissue is more ubiquitous than previously reported and may be a useful, albeit nonspecific marker of lipogenic differentiation. However, its utility in the differential diagnosis of fatty tumors appears limited.
Adipose Tissue↗
Demonstration of common sarcoma-associated antigen(s) in an established human neurogenic sarcoma cell line.
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Adenocarcinoma↗
Chimeric TLS/FUS-CHOP gene expression and the heterogeneity of its junction in human myxoid and round cell liposarcoma.
Myxoid liposarcomas have a unique and specific t(12;16)q13;p11) chromosomal translocation. The breakpoint has recently been identified and shown to involve the TLS/FUS gene on chromosome 16 and the CHOP gene on chromosome 12. This translocation causes fusion of these genes resulting in the expression of a novel chimeric TLS/FUS-CHOP message. Using the polymerase chain reaction with primer sets derived from sequences of TLS/FUS and CHOP cDNAs, we could amplify three types of the fusion transcripts from seven of seven samples of myxoid and round cell liposarcomas. In six of the seven positive samples, two kinds of chimeric messenger RNAs were found that have been reported previously. However, the last sample had a novel chimeric message that had an extra sequence of 33 bp derived from the TLS/FUS gene. Thus, it was shown that these fusion transcripts had a varying extent of the sequence of TLS/FUS gene incorporated at the site of the fusion. However, the TLS/FUS-CHOP fusion transcripts were not detected in two pleomorphic liposarcomas or in three myxoid variants of malignant fibrous histiocytomas. Our findings indicate that in liposarcomas TLS/FUS-CHOP fusion transcripts have variations at the junction of chimeric messages, which was the case for Ewing's sarcoma. Detection of the chimeric message by reverse transcription polymerase chain reaction was also suggested to be a useful approach for the diagnosis of myxoid and round cell liposarcomas that have (12;16) translocation, and for distinguishing them from pleomorphic liposarcoma and myxoid variant of malignant fibrous histiocytomas.
Adult↗
Primary and metastatic malignant tumors in soft tissue of skin. Diagnostic, surgical, and prognostic considerations for the foot.
Benign and malignant soft-tissue tumors are those that arise from mesenchymal (and some neuroectodermal) nonosteogenic and nonchondrogenic cells. The various primary malignant tumors are sarcomas with invasive and metastatic potential and are the same types that arise in the deeper tissues. In addition to sarcomas that arise directly in the dermis or subcutis, these tissue areas may be invaded by sarcomas from the deeper structures and by carcinomas and sarcomas metastatic to the skin. Dermal or subcutaneous cancers may appear clinically nondescript but are nonetheless dangerous, requiring an appropriately considered biopsy for identification and subsequent planning of patient care.
Carcinoma↗
Primary retroperitoneal sarcomas.
A retrospective analysis of 20 adult patients with primary retroperitoneal sarcomas demonstrated that most patients presented with pain and a palpable abdominal mass. Liposarcomas and leiomyosarcomas were the most common tumors. Seven of the 20 patients (35 percent) had complete tumor excision. Operative morbidity was 18 percent with no mortality. After complete resection, the 5 year survival rate was 43 percent. Thirteen patients underwent partial excision of tumor, with an operative morbidity rate of 29 percent and a mortality rate of 15 percent. No patient in our series lived more than 2 years after only partial excision. Anatomic restrictions to wide resection and local recurrence were the most important factors determining survival. Aggressive, complete surgical resection in treating primary retroperitoneal sarcomas is strongly recommended.
Adult↗
Long term results of neutron- and neutron-boost irradiation of soft tissue sarcomas.
The five-year follow-up results of 221 patients treated with neutrons or a neutron-boost at the West German Tumour Centre, Essen, are presented. 94 patients with gross tumour were treated with neutrons alone. 127 patients without gross tumour left behind post surgery were irradiated using a "mixed beam" schedule. The disease-free survival rate at five years is 62.6% for T1-, 71.5% for T2- and 28.7% for T3-tumours (p = 0.016). Significant differences were also found for various grades, i.e. 73.3% for G1-, 47.7% for G2- (p = 0.035) and 22.4% for G3-tumours (p = 0.024). Patients without microscopic tumour residue fared best with a survival rate of 86.6%, followed by patients with microscopic tumour (65.5%; p = 0.042) and patients with gross tumour (25.5%; p = 0.003) left behind. A functional limb was preserved in 86% of the patients with extremity lesions. The local control rate of patients with gross tumour was 76.5% compared with 53% in previous photon series. This finding underlines the potential biological advantage of neutrons in these tumours. Serious side effects ranged from 28% in the patients treated with neutrons for large volumes to 7% in patients treated with a neutron boost.
Evaluation Studies as Topic↗
Primary retroperitoneal sarcomas. A review of 36 cases.
A retrospective study of 36 patients with primary retroperitoneal sarcomas treated at The Norwegian Radium Hospital is presented. The median age at presentation was 57 years. The most common presenting symptom was abdominal pain. Leiomyosarcoma and liposarcoma were the most common histologic subtypes. The median survival in the whole series was 25 months. Patients with completely resected tumors had a longer median survival (59 months) than patients with incomplete resection (16 months) but the difference was not statistically significant. The malignancy grade seemed to be the most important prognostic factor and patients with low grade tumors had a significantly better outlook than those with high grade tumors.
Abdomen↗
[Results of surgical therapy of soft tissue sarcoma of the retroperitoneum].
Between 1.1.1973 and 30.6. 1993 57 patients underwent operation for soft-tissue sarcoma of the retroperitoneum. The histological classification showed in 21 cases a liposarcoma and in 14 cases a leiomyosarcoma. Other histological types like fibrosarcoma, malignant fibrous histiocytoma or malignant schwannoma were only rarely seen. Complete resection (R-0-resection) was possible in 39 cases (73.5%). 6 patients underwent partial resection (R-2-resection) and 8 patients had only an explorative laparotomy because of an unresectable tumor. To realize a complete resection in 23 cases a multivisceral resection was necessary. The postoperative staging according to AJCC showed for 47.7% of the patients a stage III- or stage IV- disease. The clinical follow-up was observed between 3 months and 14.3 years. The cumulative 5-year-survival-rate for all patients was 38.2%. The most important factor for prognosis was the complete resection, while other factors like sex and age of patients, size of the tumor and histological type did not predict outcome. After complete resection the cumulative 5-year-survival-rate was 46.7%, while after partial resection or explorative laparotomy no patient survived 5 years.
Adult↗
[Treatment of disseminated sarcomas of the soft tissues].
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Adult↗
Cellular immunity to a common human sarcoma antigen and its specific inhibition by sera from patients with growing sarcomas.
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Antigens↗
Sarcoma of the kidney: angiographic features.
Sarcomas of the kidney are highly malignant neoplasms. Abnormal vascularity can be detected in almost all types of sarcomas, but arteriovenous shunting, pooling of contrast material, and tumor staining are seldom present. Extension to renal vein and inferior vena cava may occur. While angiographic findings in our seven cases of renal sarcomas were nonspecific, this diagnosis should be considered in a relatively hypovascular neoplasm especially when the capsular arteries contribute considerably to the vascular supply. Nevertheless, statistically the most likely diagnosis of a hypovascular mass is renal cell carcinoma. Angiographic studies do not alter the management of the patient but merely suggest the diagnostic possibility of sarcoma. Angiographic diagnosis of different histologic types of sarcomas is not possible.
Adult↗