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PubMed1985

The value of adjuvant chemotherapy in the management of sarcomas in children.

Sarcomas of childhood rank fifth in incidence of malignant tumors in children younger than 15 years. Among the soft tissue sarcomas, approximately 50% are rhabdomyosarcomas. The remainder represent a heterogeneous group of diverse sarcomas which are not unique to children and include fibrosarcoma, synoviosarcoma, malignant fibrous histiocytoma, malignant schwannoma, angiosarcoma, leiomyosarcoma, and others. The most common bone cancers in childhood are osteosarcoma and Ewing's sarcoma. Although a multidisciplinary approach utilizing surgery, irradiation, and combination chemotherapy is routinely used in management of virtually all children with solid tumors, the value of adjuvant chemotherapy in select bone and rare soft tissue sarcomas is currently being tested. Multiagent chemotherapy including vincristine, dactinomycin, cyclophosphamide, and Adriamycin (doxorubicin) contribute to cure rates in 65% to 75% of children with localized rhabdomyosarcoma, Stages I to III, when combined with surgery and/or irradiation. Other drugs which hold promise include platinum, DTIC, methotrexate, and VP-16. The efficacy of similar drugs in the rarer pediatric soft tissue sarcomas other than rhabdomyosarcoma and its variants requires prospective randomized trials evaluating histologic grade, tumor size, and nodal status. It has been suggested that the high-grade sarcomas presenting with minimal tumor bulk are most sensitive to combined radiotherapy-chemotherapy, whereas the low-grade sarcomas are more resistant to such therapy. Tumor cell heterogeneity contributes to biologic diversity and response to treatment. Chemotherapy as adjuvant therapy to irradiation is currently recommended and utilized for Ewing's sarcoma with survival rates approaching 80%, and disease-free survival of approximately 75% for those with localized disease. Children with widespread and metastatic disease at presentation fare less well. Although multiple single agents exhibit response rates ranging from 40% to 60%, including cyclophosphamide, Adriamycin, dactinomycin, BCNU, mithramycin, and 5-fluorouracil, new and more effective agents are needed. Controversy regarding the value of multiagent chemotherapy in osteosarcoma has stimulated prospective randomized trials. Evaluation of local control rates as well as sites and occurrence of metastases are essential in assessing the contribution of aggressive combined modality therapy in the pediatric sarcomas. Emphasis on refinement of therapy in determining the risk/benefit ratio from adjuvant chemotherapy in pediatric sarcomas is mandatory. Enhancement of early local reactions is apparent when adjuvant chemotherapy is used with local radiotherapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Agents↗
PubMed1980

Fibrosarcoma of the breast.

A total of 5 583 symptomatic patients were referred for xeromammography at the Mammographic Clinic, Johannesburg General Hospital, between June 1974 and January 1979. Four hundred and fifty-eight carcinomas and 3 sarcomas were recorded. The incidence of carcinoma in our series was 7,9% and that of sarcoma 0,65%, while there was a 0,21% incidence of pure fibrosarcoma. Comparison is made with world literature.

Adenocarcinoma, Mucinous↗
PubMed1989

Pathologic analysis of advanced adult soft tissue sarcomas, bone sarcomas, and mesotheliomas. The Eastern Cooperative Oncology Group (ECOG) experience.

A total of 488 tumors entered in the Eastern Cooperative Oncology Group (ECOG) Study EST 3377 were evaluated histologically by a panel of pathologists from member institutions for quality control purposes. The overall agreement rate between the eligible submitting diagnosis and the pathology review panel's diagnosis was 74% (312/424). In 10% (44/424), the case was excluded because it was deemed to be nonsarcoma. In the other 16%, the disagreement concerned the type of sarcoma. The histologic type with the lowest agreement rate was rhabdomyosarcoma (17%), followed by sarcoma not otherwise specified (NOS) (27%), angiosarcoma (33%), and fibrosarcoma (48%). These figures reflect the significant degree of difficulty in the diagnosis of these tumor types. The treatment response rate of soft tissue sarcomas in the randomized study of Adriamycin (Adria Laboratories, Columbus, OH) regimens was slightly higher for those with lower grade sarcomas, i.e., 25% (four of 16) response rate for Grade 1 lesions; 22% (17/77) for Grade 2, and 21% (35/170) for Grade 3. When adjusted for type of sarcoma, there was no noticeable difference between Grade 1-2 versus 3 in response rate. A statistically significant difference in the percentage of complete responders was noted between Group A tumors (synovial sarcoma, hemangiopericytoma, sarcoma NOS, and Ewing's; 12.2%) versus Group B tumors (all other types--mostly spindle cell sarcomas; 3.5%) (P = 0.02).

Adolescent↗
PubMed1996

Lipomatous tumors.

Lipomatous tumors are a common group of mesenchymal lesions. Over the years the major changes in the classification of lipomatous tumors have included the addition of several new variants of lipoma, the use of the term atypical lipoma for well differentiated liposarcoma of the subcutaneous tissue, and recognition of the entity dedifferentiated liposarcoma. Lipomas, the most common lipomatous tumor, account for nearly one-half of all benign lesions. In their typical form they seldom present diagnostic problems for the pathologist. However, lipomas occurring in deep locations (e.g., intramuscular lipoma, perineural lipoma) or those having unusual features (e.g., chondroid lipoma, lipoma with hibernoma, cellular angiolipoma, spindle cell/pleomorphic lipoma) may be confused with liposarcoma. Recent cytogenetic studies have reaffirmed the separate nature of many of the variants of lipoma. Solitary lipomas commonly have rearrangements of chromosome 12, a finding not encountered in multiple lipomas or in spindle cell/ pleomorphic lipoma. Liposarcoma is the most common adult soft tissue sarcoma. It seldom arises from subcutaneous tissues or from preexisting lipomas, and is seldom found in children. The hallmark of liposarcoma is the immature fat cell or lipoblast. Diagnostic lipoblasts have an eccentric, hyperchromatic nucleus, which is indented or scalloped by the presence of one or more fat vacuoles. It is important that these cells occur in the appropriate histologic background because similar cells can be seen in a variety of nonlipomatous lesions (e.g., silicone reaction). Failure to apply strict criteria in identifying such cells and in noting the milieu in which they occur can lead to overdiagnosis of liposarcoma. Liposarcomas are divided into several subtypes: well differentiated, myxoid, round cell, pleomorphic, and dedifferentiated. Liposarcomas can be conceptualized as occurring in two broad groups, myxoid/round cell liposarcoma and well differentiated/dedifferentiated liposarcoma. Myxoid/round cell liposarcomas occur in middle-aged adults primarily as an extremity lesion. Tumors range from pure myxoid (low grade) to pure round cell (high-grade lesions) with some cases having transitional features. Behavior can be related to the amount of round cell areas. A consistent chromosome abnormality t(12;16) characterizes this spectrum of lesions. Well differentiated/dedifferentiated liposarcomas, in contrast, occur in late adult life as extremity or retroperitoneal lesions. They consist of mature fat interlaced with atypical hyperchromatic cells and rare lipoblasts. These lesions recur commonly, but they do not metastasize. Their behavior is strongly influenced by location, with retroperitoneal lesions having the worse prognosis. As a long-term complication of the disease, these lesions may progress histologically (dedifferentiate), a phenomenon that confers upon them metastatic potential. Dedifferentiation is largely a time-dependent phenomenon that occurs in sites in which there is a high likelihood for clinical persistence of disease (e.g., the retroperitoneum). Dedifferentiated liposarcomas occur in an age group similar to well differentiated liposarcoma, but are found far more commonly in the retroperitoneum. Most occur as de novo lesions, with only a small percentage occurring as a late complication of well differentiated liposarcoma, as described above. They consist of well differentiated areas associated with nonlipogenic sarcoma usually resembling high-grade malignant fibrous histiocytoma or fibrosarcoma. However, the range of histologic features occurring in the dedifferentiated areas is more varied than previously appreciated. Low-grade areas resembling fibromatosis or low-grade fibrosarcoma may be seen as the sole expression of dedifferentiation or may co-exist with high-grade sarcoma. (ABSTRACT TRUNCATED)

Adult↗
PubMed1980

Definitions of osteosarcoma, chondrosarcoma, and fibrosarcoma of bone.

The current definition of osteosarcoma, based on the prescence of tumor osteoid, is unsatisfactory because it fails to identify some examples of chondroblastic, fibroblastic, and anaplastic osteosarcoma having no demonstrable tumor osteoid. The tumor cells in osteosarcoma, whether osteoblastic, chondroblastic, fibroblastic, or anaplastic, contain abundant alkaline phsophatase, whereas this enzyme is scanty or absent in condrosarcoma and fibrosarcoma. It is therefore proposed that these bone sarcomas are best defined according to the origin of the constituent tumor cells and their alkaline phosphatase content: osteosarcoma--a malignant tumor of osteoblasts (alkaline phosphatase positive); chondrosarcoma--a malignant tumor of chondroblasts (alkaline phosphatase negative); and fibrosarcoma--a malignant tumor of fibroblasts (alkaline phosphatase negative).

Alkaline Phosphatase↗
PubMed1996

Molecular design of hybrid tumor necrosis factor-alpha III: polyethylene glycol-modified tumor necrosis factor-alpha has markedly enhanced antitumor potency due to longer plasma half-life and higher tumor accumulation.

We have reported that chemical modification of tumor necrosis factor-alpha (TNF-alpha) with polyethylene glycol (PEG) markedly increases its antitumor potency without any adverse side effects. MPEG-TNF-alpha, especially, in which 56% of the lysine amino groups of TNF-alpha are coupled with PEG, exhibits 100-fold more antitumor activity in vivo than native TNF-alpha in the Meth-A murine sarcoma model. In this study, we investigated the pharmacokinetics of PEG-modified TNF-alpha with various molecular sizes to clarify the mechanisms of the enhanced antitumor potency of MPEG-TNF-alpha. The plasma half-lives of modified TNF-alpha increased with increasing molecular size. The decreased plasma clearance of modified TNF-alpha was partially caused by the shielding effect of the proteolytic sites in TNF-alpha by the attached PEG and the decreased transport from blood to various tissues. Almost all native TNF-alpha was uniformly distributed to the kidney and reticuloendothelial system within 1 hr of an intravenous administration, and rapidly disappeared from these tissues at 3 hr. However, very little native TNF-alpha was transported into the tumor. The absolute distributed amount and distribution profile of modified TNF-alpha to tissues other than the tumor were the same as those of native TNF-alpha, whereas the plasma levels of the modified TNF-alpha were higher than plasma levels of the native TNF-alpha. The tumor distribution of modified TNF-alpha was markedly enhanced compared with native TNF-alpha and gradually increased over time. About 9-fold more MPEG-TNF-alpha was distributed to the tumor than native TNF-alpha. Thus, we found that the marked increase in the antitumor potency of PEG-modified TNF-alpha resulted from the enhanced blood residency and tumor accumulation. The antitumor effect of MPEG-TNF-alpha against sarcoma-180 other than Meth-A fibrosarcoma was also about 100 times greater than that of native TNF-alpha when systemically administered. The optimal PEGylation of TNF-alpha facilitated its antitumor potency and MPEG-TNF-alpha may be useful systemic antitumor therapeutic drug.

Animals↗
PubMed1975

[Palliative demolitive surgery].

Nine cases of untreatable tumour in which radical surgery was employed palliatively are presented. Three hemipelvectomies for recurrent rhabdomyosarcoma were performed. In one case, death occurred postoperatively, probably as a result of pulmonary embolism. One patient survived for 8 months, while the other is still alive after three years. Of two cases in which interscapulothoracic disarticulation was performed, survivals of 9 and 5 months were observed in subjects with fibrosarcoma in a mastectomy site and recurrent sarcoma of the humerus with ling metastases. Survival to 7 months was obtained in a case of sarcoma of the maxilla, while three patients with squama cell cancer of the mouth floor, chondrosarcoma of the mandible and botryoid sarcoma of the tonsillar fossa are still living after periods of 10 months to 2 yr. Though devoid of schematic indications, palliative demolition surgery can be considered in borderline cases where the operative risk is not high. Irrespective of "quantity", the "quality" of life remaining to the patients can be made compatible with the psychophysiological limits of the human personality.

Adolescent↗
PubMed1977

Non-specific cytotoxicity of spleen cells in mice bearing transplanted chemically induced fibrosarcomas.

Spleen cells collected from mice bearing transplanted chemically induced syngeneic fibrosarcomas non-specifically inhibited DNA synthesis of sarcoma and lymphoma target cells in vitro. Splenocytes from mice hyper-immunized against a syngeneic sarcoma specifically inhibited DNA synthesis of the tumour used for immunization. The impairment of tumour-cell DNA synthesis was associated in vitro with cytostasis, and lysis of the target cells was not seen. Since treatment with anti-theta serum and complement did not impair cytostatic action of the spleen cells, and since thymus-deprived animals showed similar activity to normal mice, T lymphocytes were not involved in non-specific cytostasis. Removal of phagocytic adherent cells by carbonyl iron markedly inhibited the cytostatic activity of the spleen cells, suggesting a role in this reaction for cells of the monocyte-macrophage series. The presence of an actively growing sarcoma was a prerequisite for the expression of non-specific cytostasis, since surgical excision resulted in complete disappearance of this activity of spleen cells.

Animals↗
PubMed1988

[Soft tissue sarcoma in the head and neck--analysis of 87 patients].

From 1964 to 1984, 87 patients with soft tissue sarcoma (excluding lymphreticulum system sarcoma) in the head and neck were treated in our hospital. All were proved by pathology. The incidence rate of fibrosarcoma was the highest (36.8%), hemangiosarcoma the lowest (5.8%). There was no liposarcoma or synovial sarcoma in this group. The most frequently involved site was the area near the nasal cavity and maxillary sinus for fibrosarcoma (66%), the base of tongue for hemangiosarcoma (60%), scalp for dermatofibrosarcoma protuberans (54%), parapharyngeal space and soft tissue of the neck for neurogenic sarcoma (45%). Metastasis rate to the lymph nodes was 16-20% for rhabdomyosarcoma, hemangiosarcoma and malignant fibrohistiocyte tumor. No distant metastasis was found in dermatofibrosarcoma protuberans and malignant fibrohistiocyte tumor. Distant metastasis rate was 10-20% for the other types. Local recurrence rate was 9.1% for dermatofibrosarcoma protuberans, 88.9% for malignant fibrohistiocyte tumor, 30-66.7% for the other sarcomas. The 5- and 10-year survival rates were 20% and 0%, 37.5% and 0%, 91.6% and 91.6% for rhabdomyosarcoma, malignant fibrohistiocyte tumor and dermatofibrosarcoma protuberans. There were differences in clinical behavior for soft tissue sarcomas in the head, neck and in the trunk. Highly malignant sarcomas, such as liposarcoma, synovial sarcoma and rhabdomyosarcoma were rare in the head and neck but the low malignant sarcomas in the head and neck were 3-10 times as common as those in the trunk. Distant metastasis rate of the fibrosarcoma was 20% in head and neck and 6.7%in trunk, the 5- and 10-year survival rates were 36% and 77.9%, 25% and 73.6%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Tumor cells induced by the v-src oncogene are heterogeneous for expression of markers of mesenchyme differentiation.

The observation that v-src-induced tumors contain tumor cells of differing morphology, notably fibroblastoid or polygonal, raised the question as to whether the tumor cells are also heterogeneous with respect to expression of markers of cellular differentiation. Of the markers tested here, consistent reactivity for tumor tissue was noted only for antibody probes reactive to muscle actin (HHF35, alpha sm-1) or to procollagen type I (SP1. D8); for any given tumor, whether induced by v-src DNA or by Rous sarcoma virus, each of these markers was found only in a subpopulation of tumor cells. The observation of marker heterogeneity in the one v-src DNA-induced tumor examined here that typed as monoclonal suggests that v-src-induced transformation is consonant with a degree of plasticity in the phenotypes of the clonal progeny of a single transformant.

Actins↗