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Identification of the viral sequence required for the generation of recovered avian sarcoma viruses and characterization of a series of replication-defective recovered avian sarcoma viruses.

The ability of transformation-defective deletion mutants of Schmidt-Ruppin Rous sarcoma virus to induce tumors and generate recovered sarcoma viruses (rASVs) was correlated with the partial src sequences retained in the transformation-defective viral genomes. Since all the transformation-defective viruses that were capable of generating rASVs retained a portion of the 3' src sequence, regardless of the extent of the 5' src deletion, and those lacking the 3' src were unable to generate rASVs, it appears that the 3', but most likely not the 5', src sequence retained in the transformation-defective viral genome is essential for rASV formation. However, rASVs derived from a particular mutant, td109, which retained a portion of the 3' src sequence, but lacked most (if not all) of the 5' src sequence, were all found to be defective in replication. Analyses of the genomic sequences of 13 isolates of td109-derived rASVs revealed that they contained various deletions in viral envelope (env), polymerase (pol), and structural protein (gag) genes. Ten isolates of rASVs contained env deletions. One isolate (rASV3812) contained a deletion of env and the 3' half of pol, and one isolate (rASV398) contained a deletion of env and pol. The one with the most extensive deletion (rASV374) had a deletion from the p12-coding sequence through pol and env. In addition, the 5' src region of td109-derived rASVs were heterogeneous. Among the 7 isolates analyzed in detail, one isolate of rASV had a small deletion of the 5' src sequence, whereas three other isolates contained extra new sequences upstream from src. Both env- and env- pol- rASVs were capable of directing the synthesis of precursor and mature gag proteins in the infected nonproducer cells. We attribute the deletions in the replication-defective rASVs to the possibility that the 5' recombination site between the td109 and c-src sequence, involved regions of only partial homology due to lack of sufficient 5' src sequence in the td109 genome for homologous recombination. A model of recombination between the viral genome and the c-src sequence is proposed to account for the requirement of the 3' src sequence and the basis for the generation of deletions in td109-derived rASVs.

Animals↗

Mechanism of oncogenic transformation by Rous sarcoma virus. I. Intracellular inactivation of cell-transforming ability of Rous sarcoma virus by 5-bromodeoxyuridine and light.

Chick embryo fibroblasts brought into stationary phase of growth by maintenance in serum-free Eagle's MEM medium were infected with the Bryan strain of Rous sarcoma virus (B-RSV) and incubated for 18 hr in the presence of 5-bromo-deoxyuridine (BUdR). The cells were then allowed to resume growth and deoxyribonucleic acid (DNA) synthesis by addition of an enriched F12 medium containing serum and RSV antibody to prevent spread of viral infection. After 48 hr, the cultures were exposed for various periods to visible light, overlaid with solid culture medium, and observed for the appearance of foci of transformed cells. In cultures treated with BUdR at the time of infection, exposure to light resulted in a suppression of focus formation of from 50 to 90% in various experiments. Treatment with BUdR for 18 hr before infection or on the day after infection, followed by exposure to light, had no effect on focus formation. In cultures in which almost all cells were infected, treatment with BUdR followed by exposure to light did not result in cell death. This suggests that suppression of transformation is not due to selective killing of infected cells by this treatment but rather to the intracellular inactivation of the transforming ability of Rous sarcoma proviral DNA.

Animals↗

Comparison of myeloproliferative sarcoma virus with Moloney murine sarcoma virus variants by nucleotide sequencing and heteroduplex analysis.

The myeloproliferative sarcoma virus (MPSV) was derived by passage of Moloney sarcoma virus (Mo-MuSV) in adult mice. Mo-MuSV variants transform fibroblasts. However, MPSV also affects erythroid, myeloid, and hematopoietic stem cells. The MPSV proviral genome, two temperature-sensitive mutants derived from it, Mo-MuSV variant M1, and Moloney murine leukemia virus (Mo-MuLV) were compared by heteroduplex mapping. MPSV wild type was found to have 1 kilobase pair deleted from the pol gene and to contain v-mos-related sequences. The 3' end of MPSV, including the oncogene-helper junctions, the v-mos gene, and the 3' long terminal repeat, was sequenced and compared with sequences of Mo-MuLV, MSV-124, and the mouse oncogene c-mos. From these data, MPSV appears to be either closely related to the original Mo-MuSV or an independent recombinant of Mo-MuLV and c-mos. Five possible explanations of the altered specificity of MPSV are considered. (i) The MPSV mos protein has properties inherent in c-mos but lost by other Mo-MuSV mos proteins. (ii) The MPSV mos protein has altered characteristics due to amino acid changes. (iii) Due to a frameshift, MPSV codes for a mos protein truncated at the amino terminal and also a novel peptide. (iv) A second novel peptide may be encoded from the 3' env region. (v) MPSV has long terminal repeats and an enhancer sequence more like Mo-MuLV than Mo-MuSV, with a consequently altered target cell specificity.

Animals↗

Transmissible Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in saliva of men with a history of Kaposi's sarcoma.

We have evaluated the physical state and infectious nature of Kaposi's sarcoma-associated herpesvirus (KSHV) in the saliva of nine persons with past or current Kaposi's sarcoma (KS). KSHV DNA in saliva had the physical characteristics of DNA present in virions. Inoculation of 293 cells with cell-free saliva fluid resulted in the persistence of KSHV DNA in culture for at least 13 passages of the cells. The addition of tetradecanoyl phorbol acetate to KSHV-infected 293 cells led to increased viral DNA. Two virus-specific RNAs were detected by reverse transcriptase PCR in 293 cells infected with cell-free saliva fluid and in cells present in saliva from subjects with KSHV salivary shedding. These results indicate that infectious KSHV can be present in saliva of patients with KS.

Cell Line, Transformed↗

Association of Kaposi's sarcoma associated herpesvirus (KSHV) DNA in bronchoalveolar lavage fluid of HIV infected individuals with bronchoscopically diagnosed tracheobronchial Kaposi's sarcoma.

OBJECTIVES: To determine the frequency of detection of Kaposi's sarcoma associated herpesvirus (KSHV), also known as human herpesvirus (HHV) type 8, DNA in bronchoalveolar lavage (BAL) fluid from HIV infected individuals with and without KS and to compare this with the detection rate in peripheral blood. Also to identify whether KSHV was associated with specific cell types in lavage fluid. METHODS: Nested PCR was used to detect KSHV DNA in BAL fluid from 41 consecutive individuals with Kaposi's sarcoma (KS) and in 41 controls with similar CD4 lymphocyte counts. Semiquantification of viral DNA was by end point titration. A positive cell sorting selection procedure was used to isolate specific BAL fluid cell types. RESULTS: KSHV DNA was detected in BAL fluid from 24 of 29 (83%) individuals with a bronchoscopic diagnosis of tracheobronchial KS. None was detected in 12 individuals with only cutaneous KS, or in 41 matched controls without KS. In five, KSHV DNA was detected in the cell depleted and cellular fractions of BAL fluid and in 1/5 in the CD14 (macrophage) fractions. None was detected in the CD19 (B lymphocyte) or CD4/CD8 (T lymphocyte) fractions. CONCLUSIONS: There was a clear association between the diagnosis of tracheobronchial KS and detection of KSHV DNA in BAL fluid. The cell type supporting KSHV in the respiratory tract is not CD 19 positive and has yet to be conclusively identified.

Bronchial Neoplasms↗

Cellular DNA content and prognosis of high-grade soft tissue sarcoma: the Scandinavian Sarcoma Group experience.

The nuclear DNA content of 148 high-grade soft tissue sarcomas of the extremities and trunk was determined by flow cytometry, using tumor material from paraffin-embedded tissue. The patients were part of a prospective randomized clinical trial on the efficacy of adjuvant single-agent chemotherapy with doxorubicin. Chemotherapy did not improve the metastasis-free survival (MFS). After a median follow-up time of 48 months (range, 2 to 97), a multivariate analysis of prognostic factors for developing metastatic disease was performed. DNA aneuploidy was found to be an independent prognostic risk factor in addition to histologic malignancy grade IV, intratumoral vascular invasion, tumor size over 10 cm, and male sex. Patients with none or one risk factor had a 5-year MFS of 79%, with two risk factors 65%, with three risk factors 43%, and with four and five risk factors 0%. About one half (78 of 148) of the patients with three factors or less belonged to a group with a MFS over 60%. The combination of different risk factors, including DNA aneuploidy, seems to be a useful prognostic model for soft tissue sarcomas, which could be of value to select high-risk patients for further trials with adjunctive therapy.

Adolescent↗

Granulocyte-macrophage colony-stimulating factor allows safe escalation of dose-intensity of chemotherapy in metastatic adult soft tissue sarcomas: a study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.

PURPOSE: This study was designed to test the feasibility of administering doxorubicin at an optimal dose-intensity (> 70 mg/m2 per 21 days) in combination with ifosfamide under recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) cover in patients with metastatic soft tissue sarcomas. PATIENTS AND METHODS: One hundred four eligible patients (of 111 entered) in 16 centers received doxorubicin 75 mg/m2 plus ifosfamide 5 g/m2 every 3 weeks for up to seven cycles. rhGM-CSF (250 micrograms/m2) was administered once or twice daily by subcutaneous injections for up to 14 days between cycles of chemotherapy. RESULTS: Full protocol dose-intensity of chemotherapy was administered to the majority of patients with only 15 of 293 cycles being complicated by febrile episodes that required hospitalization. There were two treatment-related deaths: one from septicemia and one from cardiac failure. The main toxicities attributed to rhGM-CSF were pruritus and rash. A 45% response rate (10% complete remission [CR]) was seen, with a median response duration of 9 months and median survival of 15 months. CONCLUSION: This high-dose regimen of chemotherapy was feasible under rhGM-CSF cover and produced a higher response rate and median survival than previously seen by the European Organization for Research and Treatment of Cancer (EORTC) Soft Tissue Sarcoma Group. A randomized phase III study is now underway comparing this regimen with conventional-dose doxorubicin/ifosfamide to test the dose-response relationship.

Adult↗

Adjuvant CYVADIC chemotherapy for adult soft tissue sarcoma--reduced local recurrence but no improvement in survival: a study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.

PURPOSE: To evaluate the benefit of adjuvant chemotherapy in adult patients with soft tissue sarcomas. The principal end points were freedom from local recurrence and/or metastases and overall survival. PATIENTS AND METHODS: Between January 1977 and June 1988, 468 patients entered this randomized study and 317 were considered eligible. Following complete surgical resection with or without radiotherapy, outcome in 145 eligible patients receiving cyclophosphamide 500 mg/m2 intravenously (IV) bolus on day 1, vincristine 1.4 mg/m2 IV bolus on day 1, doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) 50 mg/m2 IV bolus on day 1, and dacarbazine (DTIC) 400 mg/m2 by 1-hour infusion on days 1 to 3 (CYVADIC) cycles repeated every 28 days for eight courses was compared with that in 172 control patients. RESULTS: With a median follow-up duration of 80 months (range, 39 to 165), actuarial percentage survival figures at 7 years were compared. Relapse-free survival rates were higher for CYVADIC, 56% versus 43% (P = .007), and local recurrence was significantly reduced in the CYVADIC arm at 17% versus 31% (P = .004). In contrast, distant metastases occurred with similar frequency in both arms, 32% for CYVADIC versus 36% for control patients (P = .42), and overall survival rates were not significantly different at 63% versus 56% (P = .64). A reduction in local recurrence was only apparent in the group of head, neck, and trunk sarcomas (P = .002), but not in limb tumors (P = .31). CONCLUSION: Adjuvant chemotherapy with CYVADIC cannot be recommended outside the context of a clinical trial. Experience from this study has been used to plan a trial of neoadjuvant chemotherapy with doxorubicin/ifosfamide, which is currently in progress.

Adolescent↗

Prognostic factors in adult patients with locally controlled soft tissue sarcoma. A study of 546 patients from the French Federation of Cancer Centers Sarcoma Group.

PURPOSE: To define the prognostic factors in adult patients with locally controlled soft tissue sarcoma (STS) and to determine which patients should be considered for adjuvant treatment. PATIENTS AND METHODS: Five hundred forty-six patients with a nonmetastatic and locally controlled STS, collected in a cooperative data base by the French Federation of Cancer Centers (FNCLCC) Sarcoma Group from 1980 and 1989, were studied. Histologic slides of all patients were collegially reviewed. Initial treatment consisted of complete tumor resection with amputation in only 4% of the patients. Adjuvant radiotherapy was administered to 57.9% and adjuvant chemotherapy to 31%. Relationships between tumor characteristics were analyzed, and univariate and multivariate analyses were performed using Cox models for the hazards rate of tumor mortality, development of distant metastasis, and strictly local recurrence. RESULTS: Unfavorable characteristics with an independent prognostic value for tumor mortality were: grade 3 (P = 3 x 10(-10)), male sex (P = 1.5 x 10(-5)), no adjuvant chemotherapy (P = 5.4 x 10(-5)), tumor size > or = 5 cm (P = 3.8 x 10(-3)), and deep location (P = 4.6 x 10(-3)). Unfavorable characteristics for the development of distant metastasis were: grade 3 (P = 4 x 10(-12)), no adjuvant chemotherapy (P = 6.4 x 10(-4)), tumor size > or = 10 cm (P = 9.8 x 10(-4)), and deep location (P = 1.3 x 10(-3)). For the development of local recurrence, the unfavorable characteristics were: no adjuvant radiotherapy (P = 3.6 x 10(-6)), poor surgery (local excision) (P = 2 x 10(-4)), grade 3 (P = 7.6 x 10(-4)), and deep location (P = 10(-2)). Grade, depth, and tumor size were used to define groups of patients according to the metastatic risk. Adjuvant chemotherapy was beneficial in terms of overall survival and metastasis-free survival in grade 3 tumor patients only. Despite worse characteristics concerning tumor depth, tumor-node-metastasis (TNM) and American Joint Committee (AJC)/International Union Against Cancer (UICC) classifications and grade in patients with adjuvant radiotherapy, the latter experienced significantly fewer local recurrences than patients with no radiotherapy. CONCLUSION: Grade, tumor depth, and tumor size could be used to select patients with a high metastatic risk, for which adjuvant chemotherapy could be beneficial.

Adolescent↗

Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma.

PURPOSE: Several histologic grading systems have been validated in soft tissue sarcomas (STS), but no system is currently accepted worldwide. The National Cancer Institute (NCI) and French Federation of Cancer Centers Sarcoma Group (FNCLCC) systems were examined comparatively in the same population of patients with STS to determine which system is the best prognosticator with regard to metastasis development and tumor mortality. PATIENTS AND METHODS: Four hundred ten adult patients with nonmetastatic STS were examined. Histologic grade was established according to the NCI and FNCLCC systems in each case. The prognostic value of both systems was examined using univariate and multivariate (Cox's model) analyses, and special attention was devoted to tumors with discordant grades. RESULTS: In univariate analysis, both the NCI and FNCLCC systems were of prognostic value to predict metastasis development and tumor mortality. In multivariate analysis, high-grade tumors, irrespective of the system used, size > or = 10 cm, and deep location were found to be independent prognostic factors for the advent of metastases. Tumor grade had a higher predictive value than size or depth, and higher prognostic weight was assigned to the FNCLCC grading system in Cox models. Grade discrepancies were observed in 34.6% of the cases. An increased number of grade 3 STS, a reduced number of grade 2 STS, and a better correlation with overall and metastasis-free survival within subpopulations with discordant grades were observed in favor of the FNCLCC system. CONCLUSION: The FNCLCC system showed slightly increased ability to predict distant metastasis development and tumor mortality. The use of this system to evaluate STS aggressiveness might be favored.

Adolescent↗

Results of treatment for soft tissue sarcoma in childhood and adolescence: a final report of the German Cooperative Soft Tissue Sarcoma Study CWS-86.

PURPOSE: The goal of the second German Soft Tissue Sarcoma Study CWS-86 (1985 to 1990) was to improve the prognosis in children and adolescents with soft tissue sarcoma by means of a clinical trial comprising intensive chemotherapy and risk-adapted local therapy. PATIENTS AND METHODS: There were 372 eligible patients. A staging system based on the postsurgical extent of disease was used. Chemotherapy consisted of vincristine, dactinomycin, doxorubicin, and ifosfamide. Radiotherapy was administered early at 10 to 13 weeks simultaneously with the second chemotherapy cycle (32 Gy or 54. 4 Gy). The single dose was reduced to 1.6 Gy and given twice daily (accelerated hyperfractionation). RESULTS: The event-free survival (EFS) and overall survival rates at 5 years were 59% +/- 3% and 69% +/- 3%, respectively. The 5-year EFS rate according to stage was as follows: stage I, 83% +/- 5%; stage II, 69% +/- 6%; stage III, 57% +/- 4%; and stage IV, 19% +/- 6%. The outcome for patients with stage III disease who required radiotherapy was much better in the CWS-86 study compared with the CWS-81 study (5-year EFS, 60% +/- 5% v 44% +/- 6%; P =.053). The most common treatment failure was isolated local relapse, with 14% of patients relapsing at the primary tumor site. CONCLUSION: The improved design of the study incorporating risk-adapted radiotherapy allowed treatment to be reduced for selected groups of patients without compromising survival.

Adolescent↗

Kaposi's sarcoma-associated herpesvirus infection and Kaposi's sarcoma in Brazil.

Kaposi's sarcoma (KS) became a critical health issue with the emergence of acquired immunodeficiency syndrome (AIDS) in the 1980s. Four clinical-epidemiological forms of KS have been described: classical KS, endemic KS, iatrogenic KS, and AIDS-associated KS. In 1994, Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus type 8 was identified by Chang and colleagues, and has been detected worldwide at frequencies ranging from 80 to 100%. The aim of the present study was to evaluate the frequency of KSHV infection in KS lesions from HIV-positive and HIV-negative patients in Brazil, as well as to review the current knowledge about KS transmission and detection. For these purposes, DNA from 51 cases of KS was assessed by PCR: 20 (39.2%) cases of classical KS, 29 (56.9%) of AIDS-associated KS and 2 (3.9%) of iatrogenic KS. Most patients were males (7.5:1, M/F), and mean age was 47.9 years (SD = +/- 18.7 years). As expected, HIV-positive KS patients were younger than patients with classical KS. On the other hand, patients with AIDS-associated KS have early lesions (patch and plaque) compared to classical KS patients (predominantly nodular lesions). This is assumed to be the result of the early diagnose of KS in the HIV-positive setting. KSHV infection was detected by PCR in almost all cases (48/51; 94.1%), irrespectively of the clinical-epidemiological form of KS. These results show that KSHV is associated with all forms of KS in Brazilian patients, a fact that supports the role of this virus in KS pathogenesis.

AIDS-Related Opportunistic Infections↗

Viral latent proteins as targets for Kaposi's sarcoma and Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) induced lymphoma.

Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) is present in all Kaposi's sarcoma tumor cells as well as in several lymphomas that are linked to this agent. Every tumor cell expresses the viral latent protein LANA, which is required for KSHV latent replication and proper segregation of the viral episome. In certain tumors, other latent KSHV proteins (LANA-2/vIRF3, v-cyclin, v-IL6) are expressed as well. Since all herpesviruses persist for life in infected individuals, only eradication of latent virus can cure infection. The KSHV latent genes serve as bona fide tumor markers, but do they also provide targets for anti-tumor and/or anti-viral drugs? To decide this question we review the known biochemical interactions between KSHV latent proteins and their viral and cellular partners. Recent epidemiological studies show that KSHV lytic replication precedes KSHV associated cancers. Gancilovir has been linked to KS tumor regression, which implicates the KSHV-encoded polymerase as a potential intervention point. Yet, KSHV specific transactivators might represent more specific targets, as they have no cellular homologs. In particular Rta/orf50 is necessary and sufficient for lytic replication and deserves serious consideration as a target for KSHV-specific antivirals.

Antigens, Viral↗

Surgical margin in soft tissue sarcoma. The Scandinavian Sarcoma Group experience.

Two-hundred and forty adult patients with a high-grade soft tissue sarcoma were treated surgically in 18 hospitals participating in the Scandinavian Sarcoma Group Protocol I. The patients were randomized to either postoperative doxorubicin or control; patients whose surgical margin was judged marginal also received radiotherapy. The outcome after different surgical margins was analyzed in 185 tumors of Grades III or IV in the extremities. The total cumulative local tumor control was 91 percent (168 of 185) after a median of 47 months. The cumulative local control rates in the surgical groups were: compartmental or wide amputation--37/37 (100 percent), compartmental local excision--23/24 (96 percent), wide local excision--77/84 (92 percent), marginal excision and radiotherapy--19/21 (90 percent), and marginal excision alone (reevaluated margin)--12/19 (63 percent, significantly lower than others). The risk of local recurrence was 13 times higher after marginal than after compartmental surgery (P = 0.02) and 3 times higher if the tumor was larger than 10 cm (P = 0.05). The treatment with doxorubicin did not influence the risk of local recurrence. The survival rates did not differ significantly in the groups.

Combined Modality Therapy↗

Human herpesvirus 8 in Kaposi's sarcoma and Kaposi's sarcoma-mimicking vascular tumors.

Kaposi's sarcoma (KS) had been a rare and unusual vascular tumor until a recent epidemic of a disseminated and fulminant form of KS in AIDS patients. Infectious agents have been suspected of causing KS, and recently partial genomic DNA sequences of human herpesvirus 8 (HHV8) have been identified in AIDS-associated KS lesions. Since then, genomic DNA sequences of HHV8 have been isolated in other forms of KS. Although the partial genomic DNA sequence of HHV8 was reported to be, if rare, identified in vascular tumors other than Kaposi's sarcoma (KS), the presence of HHV8 in a very large fraction of KS indicates that detection of HHV8 by PCR is a useful auxiliary tool in differentiating KS from other KS-mimicking vascular tumors. We examined whether the 233-bp segment of the viral DNA was detected in Korean patients with KS and other KS-mimicking vascular tumors. HHV8 sequences were identified in all of nine classic type of KS but not in three epithelioid hemangioendotheliomas and seven angiosarcomas. Our results confirm the relatively restricted distribution of HHV8 and also argue against the likelihood of secondary colonization of KS cells by HHV8.

Adult↗

Chemotherapy in Ewing's sarcoma. The Scandinavian Sarcoma Group experience.

During the past 15 years the Scandinavian Sarcoma Group has treated 140 patients with Ewing's sarcoma. Two protocols have been used. SSG IV included 52 patients between 1984 and 1990 and SSG IX, 88 patients since 1990. After 5 years of treatment, local recurrences occurred in 19% of the patients (M0 + M1) in the SSG IV group and 10% in the SSG IX group. Distant metastases developed in 57% of the M0-patients in the SSG IV group and in 33% in the SSG IX group. Tumor-related survival (overall) of M0-patients was 49% in SSG IV and 70% in SSG IX, and the metastasis-free survival rate 45% and 58%, respectively. Patients having a localized extremity tumor had a survival rate of 90% (SSG IX). In both treatment groups, good responders to chemotherapy had a better survival rate than poor ones (SSG IV, p < 0.02, GI-II vs. G II-IV and SSG IX, p < 0.003, GI-III vs. G IV). In conclusions local control and survival rates were better with SSG IX than SSG IV.

Adolescent↗

Radiation treatment of Ewing's sarcoma and osteogenic sarcoma.

At the Princess Margaret Hospital, Toronto, during the period 1960 to 1975, radiation therapy was given to 59 patients with Ewing's sarcoma without overt metastases. Over this period treatment was modified to include, as well as irradiation to the primary tumour, total body irradiation (TBI) and chemotherapy according to various regiments. The 5-year survival rate of 38% in 26% patients who received TBI suggests that this may be of value. In patients with osteogenic sarcoma preoperative irradiation was not found to be of value. Recently the resection of pulmonary metastases combined with chemotherapy has increased the survival rate. When the primary site makes resection impracticable, the response to irradiation and chemotherapy is encouraging. Three cases so treated are described.

Adolescent↗

Guidelines for the surgical management of soft-tissue sarcoma. Report of the Canadian Sarcoma Group.

The Canadian Sarcoma Group was formed in 1985 by interested surgeons, oncologists and pathologists. In the evaluation of new protocols, standard surgical guidelines have been developed which incorporate the concepts of multimodality therapy, particularly radiotherapy and chemotherapy. Also defined are the procedures performed: biopsy, marginal resection, wide local excision, radical resection and the principles to be considered when doing a diagnostic biopsy and a curative resection, particularly with limb salvage in mind. To optimize local control of the disease, centres treating sarcomas should have access to computed tomography, radionuclide scanning, to radiation and medical oncologists, and members of other surgical specialties. This team approach increases survival by 10% and also provides the best circumstances in which to study adjuvant therapy. Surgical guidelines are also essential in order to compare the results of different clinical trials.

Biopsy↗