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PubMed1975

The role of diagnostic radiology and radiation therapy in the management of soft tissue sarcomas in children.

Soft tissue sarcomas are the fourth most frequent solid tumors in children. They arise at many sites, most frequently in the orbit, head and neck, and pelvis. Diagnostic radiologic studies play an integral role in patient evaluation, allowing direct visualization of the primary lesion, its vascular supply, its direct and regional extensions; of distant metastases; and of anomalies. They aid in staging and selecting treatment, and later, in evaluating results. Radiation therapy is a vital tool in today's multidisciplinary approach. Irradiation has produced a 90% recurrence-free rate, and a 67% cure rate, for orbital rhabdomyosarcoma. A similar improvement in local tumor control rates may apply at other primary sites when an adequate dose is delivered to the affected volume. Multidrug chemotherapy programs provide hope for an increased cure rate. Sufficient time has not yet elapsed to judge fully the late anatomical and physiological costs of these more vigorous multidisciplinary treatments.

Adolescent↗
PubMed2007

Analysis of germline and tumor mutations of p53 gene in familial occurrence of soft tissue sarcomas.

BACKGROUND: Familial soft tissue sarcomas are extremely rare. There is little information available on the clinical features and molecular findings of the hereditary occurrence of mesenchymal tumor. PATIENTS AND METHODS: A woman and her younger brother had malignant fibrous histiocytoma (pleomorphic type) and liposarcoma (pleomorphic type) in the lower limbs, respectively. Analysis of p53 mutations in exons 5-9 of the tumor and in germ-line was done. RESULTS: A guanine to adenine substitution occurred in CGC, codon 175 of exon 5 in p53 gene, to CAC in the tumor sample of Case 1. Likewise, a thymine to cytosine substitution occurred in TTT, codon 270 of exon 8 in p53 gene, to TCT in tumor sample of Case 2. Germline mutations were not seen in the either patients. CONCLUSIONS: Different missense mutations of p53 were detected in each tumor, however no germline mutations of p53 were found. The alteration of codon 175 in Case 1 is relatively common mutation. On the contrary, the mutation in codon 270 in Case 2 was extremely rare in cancers. Further molecular investigation is needed to understand the mechanism in familial occurrence of sarcomas.

Female↗
PubMed2005

Limb sparing approach: adjuvant radiation therapy in adults with intermediate or high-grade limb soft tissue sarcoma.

BACKGROUND: Limb soft tissue sarcomas (STS) are currently treated with limb sparing surgery (LSS) followed by radiation therapy (RT). PATIENTS AND METHODS: Between October 1994 and October 2002, 133 adult patients with intermediate or high-grade limb STS were approached by LSS+RT. RESULTS: RT related toxicity was manageable, with a low rate of severe effects. At 4-year median follow-up, there were 48 recurrences of any type, 23 of isolated local failure, and 35 of systemic spread w/o local failure. DFS and OS were influenced by disease stage II vs I, primary site in the upper limb vs lower limb, MPNST vs other types, induction therapy vs no induction, adequate resection vs marginal resection or involved margins, and good response to induction therapy vs bad response. DFS and OS were Patient's age and sex, tumor depth, acute or late toxicity of RT, or the interval of time between the date of definitive surgery and the start of RT did not affect DFS and or OS. CONCLUSIONS: The RT protocol is applicable in the era of complicated, expensive and time-consuming 3D therapy. Our results of LSS+RT in adults with limb HG STS are satisfactory.

Adolescent↗
PubMed2006

Increased risk of malignancies in a population-based study of 818 soft-tissue sarcoma patients.

Soft-tissue sarcomas (STS) have been associated with various rare cancer syndromes and occur at increased frequencies in survivors of childhood cancer. Also adult patients with STS have been suggested to be at an increased risk of additional malignancies. After exclusion of syndrome-associated and radiation-induced sarcomas, we studied multiple primary malignancies in a population-based cohort of 818 patients with primary STS of the extremities and the trunk wall. In total, 203 other malignancies developed in 164 (20%) patients median 10 (0-32) years before and median 4 (0-35) years after the sarcoma diagnosis. Standardised morbidity ratios (SMRs) were determined for primary malignancies following a STS. Hereby individuals who had developed a STS were identified to be at increased risk of second primary malignancies (SMR for all malignant tumours=1.3; 95% CI=1.0-1.5; P=0.02) with STS being the only specific tumour type that occurred at an increased risk (SMR=17.6; 95% CI=8.1-33.5; P<0.001). Hence, this population-based series demonstrates a high frequency of second primary tumours among STS patients and indicates a particularly increased risk of developing a new STS.

Adolescent↗
PubMed1996

Diagnosis and treatment of soft tissue sarcomas in adults.

Soft tissue sarcomas account for approximately 1% of all malignancies. They constitute a wide range of different tumor types with very different clinical courses and treatment sensitivities. Our understanding of the molecular mechanisms of tumor growth in sarcomas is increasing rapidly. These new data will probably lead to drastic changes in our current classification systems, which are primarily based on routine microscopy. This might also bring about a more detailed and reliable prognostic evaluation in individual tumors. Hopefully, this knowledge will guide us towards a more rational and more successful development of new therapies. Current surgical approaches and treatment protocols are more or less well defined. Knowledge on when to use ionizing radiation for local control is reasonably clear. Major difficulties however remain for both these treatment modalities in cases of both truncal and retroperitoneal sarcomas. The lack of new very active chemotherapeutic agents against this group of diseases has remained unchanged in the past years, although both the taxanes and the topoisomerase I inhibitors show some activity.

Adult↗
PubMedDate not supplied

Transfection with mdm2-antisense or wtp53 results in radiosensitization and an increased apoptosis of a soft tissue sarcoma cell line.

Soft tissue sarcomas (STS) are mostly resistant after radiation treatment and are characterized by a rather low rate of apoptosis. The aim of this study was to test, in the p53 mutant STS cell line US8-93, the effect of a combined treatment with DNA transfection--either with mdm2 antisense oligodesoxynucleotides (mdm2-AS) or with a wild-type p53-plasmid (wtp53)--and the effects of irradiation on radiosensitivity. Mdm2-sense oligodesoxynucleotides (mdm2-SE) and a GFP-plasmid (GFP) were applied as controls. In order to evaluate the treatment radiation sensitization (clonogenic survival), apoptotic cell death and P53/MDM2-protein expression were determined. A moderately increased radiation sensitization was observed when comparing clonogenic survival after 2 Gy irradiation between cells transfected either with the control mdm2-SE (48%) or with mdm-2 AS (30%). At the same irradiation dose, clonogenic survival of wtp53-plasmid transfected cells (32%) was about 2-fold less than in the cells transfected with the control GFP-plasmid (61%). This enhancement factor of radiation sensitization was increased by about 3-fold at 4 Gy irradiation. Furthermore, an increase in apoptotic cells was already detectable by up to 7.7% (mdm2-AS) in comparison to 3.1% (mdm2-SE control) 72 hours after transfection. In parallel, the percentage of apoptotic cells could be further elevated after subsequent irradiation with 12 Gy by up to 15% (mdm2-AS) compared to 5.7% (mdm2-SE control). A striking result was obtained with the combined treatment of a wtp53 and 12 Gy irradiation which produced in 25% and 38.9% of apoptotic cells 48 hours and 72 hours after transfection, respectively. We can therefore conclude that the sensitivity of radiation therapy is enhanced by DNA transfection with wtp53 or mdm-2 AS ODNs for the correction of the p53-mdm2 balance in STS in vitro.

Apoptosis↗
PubMedDate not supplied

Management of retroperitoneal soft-tissue sarcoma.

Retroperitoneal soft-tissue sarcoma is a rare and unusual entity, comprising about 0.1% of all tumors. Optimal outcome depends on a thorough understanding of its clinical behavior. These tumors tend to be large and have extensive regional involvement by the time they present. Complete surgical extirpation, which may require en-bloc resection of multiple organs, is the treatment of choice for patients who are deemed to be surgical candidates. Chemoradiation has not been proven to extend survival, and treatment toxicities may limit their usefulness. Re-resection of localized recurrent disease may extend survival and therefore should be attempted, when possible. Close follow-up with serial computed tomographic scans is recommended in order to detect early recurrent disease and should continue beyond 10 years.

Chemotherapy, Adjuvant↗
PubMed1994

[Soft tissue sarcomas: general review].

Soft tissues sarcomas are an heterogeneous group of neoplasms. Their epidemiology is still poorly known. Great strides have been made in the genetic study over the last few years. Histologic grade, tumor size and deep location are the main independent prognostic factors in multivariate analysis using the Cox model. Overall 5-year survival is approximately 50% in most of the studies. Surgical conservative treatment associated with radiotherapy is actually preferred to radical surgery, because no survival difference is found between the two treatments. Radiation therapy modalities are discussed: preoperative, postoperative irradiation, interstitial brachytherapy. Doxorubicin, ifosfamide and DTIC are the most efficient drugs. However, response rates obtained with polychemotherapy are still less than 50%. High-dose chemotherapy is an encouraging concept. Edatrexate and Taxotere show interesting response rates in phase II clinical trials. Adjuvant chemotherapy efficiency is probably low: a meta-analysis shows a 5-year survival increase of 9%. Neoadjuvant chemotherapy allows a high rate of conservative treatment.

Antineoplastic Agents↗
PubMed1980

[Adjuvant chemotherapy in soft tissue sarcomas].

21 patients with soft tissue sarcomas were treated after surgery with adriamycin alone or in combination with other drugs. 13 patients had additional local radiotherapy. 12 of thde 21 patients received chemotherapy as an adjuvant to surgery. 19 patients concurrently receiving palliative treatment for advanced soft tissue sarcoma in the form of adriamycin and adriamycin combinations served as controls. Results collected to date point to an improvement in the prognosis of soft tissue sarcomas, when radical surgery is followed by intensive subsequent cytostatic treatment. However, the present results await confirmation from prospective randomized studies now taking place. Some of the side effects of this treatment were very pronounced and led to the premature interruption of the trial in 24% of cases.

Adolescent↗
PubMed2003

Pediatric soft tissue sarcomas.

Many of the soft tissue sarcomas that occur in children are of the same histology as those in adults; however, the relative prevalence of these sarcomas is different between children and adults. In some cases, the biologic behavior of pediatric sarcomas is more benign than that in adults. Treatment for sarcomas in children is also different. Pediatric sarcomas are more commonly responsive to chemotherapy. Furthermore, in children who are still growing, surgery and radiation are associated with higher morbidity than in adults. This article discusses the diagnosis and treatment of rhabdomyosarcoma and undifferentiated sarcomas, with an emphasis on surgical considerations, and the diagnosis and treatment of nonrhabdomyosarcomatous soft tissue sarcomas in children.

Child↗
PubMed1995

Systemic adjuvant chemotherapy for soft tissue sarcomas.

Adjuvant chemotherapy for soft tissue sarcoma remains investigational. Continued study of multidisciplinary treatment programs in high-grade sarcomas in formal clinical trials remains a priority. The National Cancer Institute is currently conducting a randomized trial of postoperative adjuvant doxorubicin and ifosfamide as compared with observation in high-grade sarcoma. The completion and outcome of this trial will contribute to this ongoing debate. Finally, a better understanding of the biology of soft tissue sarcoma that determines subsequent clinical course may serve as a foundation for further investigation.

Antineoplastic Agents↗
PubMed1992

Surgical and adjuvant radiation therapy of resectable retroperitoneal soft tissue sarcomas in adults.

Primary soft tissue sarcoma of the retroperitoneum is a rare disease. A series of 11 evaluable adult patients with retroperitoneal soft tissue sarcomas is reported. These patients were treated with complete surgery and adjuvant radiation therapy (total dose from 50 to 64 Gy) using an 18 MeV linear accelerator. After a median follow-up of 48 months (range, 6-84), 4 patients had a local-regional recurrence, 3 had distant metastases, and 4 died of progressive disease. Four-year estimated disease-free survival was 54.5% and overall survival was 70%. Treatment was well tolerated by most patients: 7 patients experienced moderate gastrointestinal toxicity, mainly nausea and diarrhea, during radiotherapy; 2 cases had weight loss > 15% at the end of the therapy; and chronic ileitis was observed in 2 cases. We conclude that adjuvant radiotherapy seems to reduce the incidence of local-regional recurrences in these patients. No radiation-induced irreversible injury was observed, but one young woman had amenorrhea after radiotherapy. Controlled clinical trials are warranted to define the role and effectiveness of adjuvant radiotherapy and/or chemotherapy in retroperitoneal soft tissue sarcomas.

Adult↗
PubMed1998

Proliferative activity (MIB-1 index) is an independent prognostic parameter in patients with high-grade soft tissue sarcomas of subtypes other than malignant fibrous histiocytomas: a retrospective immunohistological study including 216 soft tissue sarcomas.

AIMS: To evaluate the prognostic value of tumour proliferative activity, p53 accumulation and bcl-2 expression in a retrospective series of 216 patients with soft tissue sarcomas (STS). METHODS AND RESULTS: The immunohistochemical analyses were performed on formalin-fixed, paraffin-embedded tissue. The proliferative activity was assessed by use of the monoclonal antibody MIB-1 and evaluated in multiple, random systematic sampled fields of vision. The percentage of proliferating cells (the MIB-1 index) ranged between 1% and 85% (median 12%). A significant increase in mean MIB-1 index was seen with increasing histological malignancy grade. Variation in the incidence of p53 accumulation and bcl-2 positivity among different histological subtypes was observed. p53 accumulation was frequent in synovial sarcomas and leiomyo- and rhabdomyosarcomas, whereas bcl-2 preferentially was expressed in synovial sarcomas. Univariate analysis identified patient age, tumour size, histological grade of malignancy, MIB-1 index and p53 accumulation as significant prognostic parameters. Multivariate Cox analysis, including tests for interaction terms between histological subtypes and MIB-1 index, showed independent prognostic effect of MIB-1 index and tumour size in patients with high-grade tumours of other subtypes than malignant fibrous histiocytoma (MFH). CONCLUSIONS: Histopathological malignancy grading is the most important single prognostic factor for overall survival in STS, but estimation of MIB-1 index is useful for identifying the least favourable subgroup of high grade STS of other subtypes than MFH, for whom adjuvant therapy may be indicated.

Adolescent↗
PubMed1999

[Current diagnosis and therapy of soft tissue sarcomas in the adult].

Soft tissue sarcomas embrace a wide variety of rare tumours. This often means excision without wide margins, and the unexpected malignancy leads to diversity of postoperative treatment. As a rule all lesions of a soft tissue tumour should be biopsied if persisting for more than 6 weeks. The extent of the biopsy is determined by the tumour characteristics, but should not aggravate later resection of a malignant tumour. Preoperative diagnostic studies should be standardised and include MNR, while the tumour is characterised according to the recent edition of the UICC GTNM system. The primary tumour should be excised in a limb-sparing way with wide margins, if necessary including the neighbouring fascia. Local recurrence should be approached aggressively like primary tumours, with curative intention. In cases of distant metastases, which usually occur in the lungs, a grading-associated approach is necessary. In G3 metastases chemotherapy should be administered before the surgical intervention. Radiation therapy is saved for patients in whom the tumour cannot be resected with wide margins or is larger than 10 cm maximum diameter. In the light of current knowledge, radiation therapy should be given as an adjuvant for patients whose tumour was resected without wide margins and for tumours larger than 10 cm in diameter. The use of palliative chemotherapy is still controversial and identification of new prognostic markers for patient selection is necessary. Since most patients with soft tissue sarcoma die from distant metastases and not the primary or locally recurrent tumour, the need for effective chemotherapy in an adjuvant setting is obvious. Controlled studies with as many enrolled patients as possible are necessary if valid data are to be collected. The management of soft tissue sarcoma patients is in principle multidisciplinary and should be confined to specialised centres.

Humans↗
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↗
PubMed1993

The use of recombinant human granulocyte-macrophage colony-stimulating factor with combination chemotherapy in the treatment of advanced adult soft-tissue sarcomas: early results from the EORTC Soft-Tissue and Bone Sarcoma Group.

We gave the "optimal" dose of doxorubicin (75 mg/m2) with ifosfamide (5 g/m2), the two most active agents against metastatic soft-tissue sarcomas, in an attempt to determine the feasibility of administration of these doses in combination. To offset complications arising from the myelosuppression associated with this regimen, recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF, 250 micrograms/m2 daily) was given by subcutaneous injection during the intervals between courses of chemotherapy. In all, 111 patients with progressive metastatic soft-tissue sarcoma were entered, 104 of whom were eligible for preliminary analysis. Use of rhGM-CSF allowed full doses of chemotherapy to be given to the majority of patients, although cumulative thrombocytopenia became a dose-limiting toxicity during subsequent courses. Two treatment-related deaths occurred, one from presumed septicemia while the patient was at home and one as a result of cardiac failure. An overall response rate of 45% was achieved. The activity of this high-dose combination (with rhGM-CSF) will be compared with that of standard treatment doses in a future phase III randomized trial.

Adult↗