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PubMed2004

Emerging treatments for soft tissue sarcoma of adults.

Soft tissue sarcomas are a heterogeneous group of malignancies arising from mesenchymal tissues. Patients can present with a localised tumour (primary or local recurrence) at different sites (e.g., extremity, abdomen) or metastatic disease, which may require different treatment strategies. Is the surgical resection of a localised sarcoma enough or is it better to give an additional treatment like adjuvant and/or preoperative radiotherapy and/or chemotherapy? Which chemotherapy should be selected in the first or second line situation? Do new treatment options exist, such as targeted therapies? This review provides answers to some of these questions. To decide on consecutive treatment steps, it is important to know as many relevant factors as possible at first presentation. Therefore, the first part of this review discusses the specific characteristics and prognostic factors of importance for treatment planning. A short summary of current therapy strategies and existing standards is then given. The main body of the review summarises information on new and emerging clinical compounds for patients with soft tissue sarcoma of adults, including recent developments of targeted therapy.

Adult↗
PubMedDate not supplied

New chemotherapeutic strategies for soft tissue sarcomas.

Advanced soft-tissue sarcomas are still incurable in the vast majority of patients. The currently available standard methods of treatment such as surgery, radiation therapy, and chemotherapy have a very modest impact on the natural history of advanced soft tissue sarcomas. Nevertheless, until new strategies become widely available and applicable to this disease, we are obligated to optimize the current resources and make the best use of these modalities. We discuss the approaches of standard chemotherapy used in a dose-intensive fashion (especially in high-risk patients at an earlier stage), attempts to find new drugs with activity in this disease, and tests of the concepts of anti-angiogenic and differentiation therapy. To improve cure rates, patients and physicians must be encouraged to participate in multidisciplinary clinical trials.

Antineoplastic Agents↗
PubMed1992

Treatment of soft tissue sarcoma in childhood and adolescence. A report of the German Cooperative Soft Tissue Sarcoma Study.

BACKGROUND: In the first German soft tissue sarcoma (STS) study, CWS-81, 344 patients younger than 19 years of age who had previously untreated soft tissue sarcoma were studied. For this analysis, there were 218 patients with chemosensitive STS (Group A: rhabdomyosarcoma [RMS], synovial sarcoma, extraosseous Ewing sarcoma, leiomyosarcoma, undifferentiated sarcoma, and malignant peripheral neuroectodermal tumor) who could be studied for a minimum potential follow-up time of 6 years. METHODS: A staging system based on the postoperative extent of the disease was used. The chemotherapy for Stage I-III disease consisted of vincristine, dactinomycin, cyclophosphamide, and doxorubicin (VACA). Patients with metastatic disease and patients with Stage III disease who failed to respond to VACA were given ifosfamide instead of cyclophosphamide. The definitive procedure for local tumor control (either no radiation exposure, 40 Gy, or 50 Gy) for patients with Stage II-III disease depended on the tumor status at second-look surgery after 16 weeks of chemotherapy. RESULTS: The rates of disease-free survival (DFS) and survival after 5 years was 61% +/- 4% and 57% +/- 4%, respectively, in group A; for patients with nonmetastatic tumors (Stages I-III), the rates were 69% +/- 4% and 72% +/- 4, respectively. Patients with nonmetastatic rhabdomyosarcoma had a similar prognosis: the survival rate was 73% +/- 4%, and the DFS rate was 68% +/- 4%. There was no difference in prognosis between patients with Stage I and and those with Stage II disease (DFS rate, 88% +/- 5% and 88% +/- 6%, respectively). The DFS rate for patients with Stage III disease was 54% +/- 5% and for those with Stage IV, 11% +/- 5%. Lack of local tumor control was the primary cause of therapy failure: 10% of patients with localized disease did not achieve complete remission, whereas 18% who were in complete remission experienced local relapse. The most important prognostic factors were tumor size (P = 0.005) and the degree of tumor regression after primary chemotherapy (P = 0.007). The prognosis also differed according to primary site: paratesticular tumors had the best prognosis, whereas tumors located in the parameningeal regions of the head and neck had the worst prognosis (DFS rate, 96% +/- 4% versus 49% +/- 7%, respectively). CONCLUSIONS: The following conclusions were drawn from the CWS-81 study: (1) intensive chemotherapy (VACA for 35 weeks) provides long-term control for most patients with Stage I-II disease; (2) patients with primary unresectable tumors (i.e., Stage III) who achieve complete remission with chemotherapy alone have the same prognosis as patients with postoperative disease of Stages I and II; (3) tumor size and the degree of tumor regression after primary chemotherapy influence outcome and thus can be used as a basis for risk-adapted therapy.

Adolescent↗
PubMed1991

Diagnosis and management of retroperitoneal soft-tissue sarcoma.

Retroperitoneal soft-tissue sarcomas are locally invasive tumors that remain occult for long periods and grow quite large due to the abdominal cavity's remarkable ability to accommodate these slowly expanding masses with a paucity of attendant symptoms. An open biopsy is required to establish diagnosis definitively. Despite improved imaging techniques and preoperative and intraoperative patient management, resectability has not changed significantly in the past 20 years. Even with an aggressive operative approach, only one half the tumors can be resected completely, and of those, more than 90% recur locally and result in the death of the patient. The addition of adjuvant radiotherapy or chemotherapy has not altered this pattern of local failure, in contrast to promising results with extremity soft-tissue sarcoma. Because of the rarity of these tumors, there is an urgent need to establish a national retroperitoneal sarcoma registry and to form cooperative intergroup studies to evaluate, treat, and apply innovative multimodality combination therapies to these otherwise lethal tumors.

Antineoplastic Agents↗
PubMed2001

[Epidemiology of soft tissue sarcomas in adults].

INCIDENCE: Soft tissue sarcoma accounts for a approximately 1% of all cancers. Excluding Kaposi sarcoma, the incidence of soft tissue sarcoma has remained stable in Europe (3-4/100,000). ENDOGENOUS FACTORS: Endogenous factors are related to rare genetic syndromes (Li-Fraumeni syndrome, neurofibromatosis, Werner syndrome, bilateral retinoblastom). EXOGENOUS FACTORS: Exogenous factors associated with soft tissue sarcoma are essentially iatrogenic: radiation therapy (prevalence of radiation-induced sarcoma: 0.17-0.21%) and chronically edematous arms after radical mastectomy for breast cancer (Stewart-Treves syndrome). Many studies suggest that environmental or occupational exposure to chlorophenol, phenoxy-herbicides or dioxin increase the risk of soft tissue sarcoma. FURTHER RESEARCH: Little is known about the epidemiology of soft tissue sarcoma. Case-control studies are needed.

Adult↗
PubMed1999

Use of brachytherapy to preserve function in children with soft-tissue sarcomas.

Pediatric soft-tissue sarcomas are managed with a multimodality treatment program that includes surgery, chemotherapy, and external-beam radiotherapy (teletherapy). The use of teletherapy in young children can result in significant long-term toxicities (especially growth retardation of bones and organs). Brachytherapy, if feasible, is an attractive alternative for the treatment of pediatric soft-tissue sarcomas, since it irradiates small volumes and, thus, may potentially minimize complications. Aggressive chemotherapy is used to achieve systemic control and tumor shrinkage, thereby facilitating conservative surgery and brachytherapy. The brachytherapy techniques used in children are similar to those employed in adults. Low-dose-rate (LDR) brachytherapy with manually afterloaded removable iridium-192 is commonly used, although it is associated with some radiation exposure hazards. Low-energy radionuclides (e.g., iodine-125) and remote afterloading technology have been used to reduce radiation exposure hazards. Brachytherapy, in conjunction with chemotherapy and surgery but without supplementary teletherapy, has produced good local control with acceptable late complications in selected patients with localized tumors. Brachytherapy can also be used as a boost to moderate dose external-beam radiotherapy for more extensive tumors. The use of newer modalities, such as high-dose-rate, pulsed-dose-rate, and intraoperative brachytherapy, has allowed brachytherapy to be given to younger children and infants, but the long-term morbidities of these modalities need to be established.

Brachytherapy↗
PubMed1992

Does malignant transformation of benign soft-tissue tumours occur? A clinicomorphological study of ten initially misdiagnosed soft-tissue sarcomas.

Ten soft-tissue sarcomas out of a consecutive series of 201 neoplasms are described, in which the clinical histories were suggestive of malignant transformation of a benign lesion excised from the same location 2-97 months before. Each of the 10 preceding soft-tissue neoplasms was reviewed histologically and reclassified as either highly (n = 8) or moderately differentiated (n = 2) sarcomas. Irrespective of the primary treatment, these initially misdiagnosed tumours showed an overall better prognosis than the whole group of soft-tissue sarcomas (5- and 10-year survival rates 76% versus 44%, and 52% versus 30% respectively). Their clinical course was, however, characterized by up to 6 (mean 2.9) local recurrences. From the total series of 201 tumours the authors conclude that soft-tissue sarcomas other than malignant schwannomas in the setting of von Recklinghausen's disease only exceptionally, if ever, arise from benign precursors.

Adult↗
PubMed1988

Cellular heterogeneity. Explanation for changing of tumor phenotype and biologic behavior in soft tissue sarcomas.

Many human soft tissue sarcomas are known to show variable structures in a given tumor and to be able of changing the histological feature during the course of the disease. These facts prompted an experimental study in order to ascertain if by use of long-term cultures of an established rat fibrosarcoma cell line (RFS) in respective inoculation tumors a histological picture different from the original fibrosarcoma could be produced. It was found that inoculation tumors generated by later subcultures partly corresponded to tumors with features of malignant histiocytomas and malignant fibrous histiocytomas. In a further experiment we attempted to initiate metastatic dissemination of a primarily non-metastasizing xenotransplanted RFS sarcoma in nude mice. By repeated diminution operations comparable to inadequate tumor surgery in human metastasis formation in lung parenchyme was attained. Taking into account cellular heterogeneity as basically responsible for the phenomena observed, different causal aspects concerning the experimental results are discussed. We deduce from our findings that the concept of histogenetic classification of soft tissue sarcomas should be replaced by an interpretation according to the actual differentiation. This also applies to malignant fibrous histiocytomas which are at least in part mesenchymal tumors and not descendants of mononuclear phagocytic cells and may originate by a dedifferentiation process of otherwise defined sarcoma types.

Animals↗
PubMed1993

Phase II study of miltefosine (hexadecylphosphocholine) in advanced soft tissue sarcomas of the adult--an EORTC Soft Tissue and Bone Sarcoma Group Study.

The EORTC Soft Tissue and Bone Sarcoma Group conducted a phase II study with oral miltefosine at a dose of 50 mg thrice daily in patients with metastatic soft tissue sarcomas. No responses were seen in 18 evaluable patients. Toxicity consisted mainly of nausea/vomiting. It is concluded that oral miltefosine has no activity in soft tissue sarcoma.

Administration, Oral↗
PubMed1999

Imaging of soft tissue sarcomas.

Imaging of soft tissue sarcomas is critically important in the management of these patients. Whether CT scanning or MR imaging is the best test remains controversial; studies to support either modality exist and are reviewed. An integrated approach using clinical algorithms and radiologic studies to preoperatively stage and follow these patients seems to provide optimal care.

Abdominal Neoplasms↗
PubMed1996

Pediatric soft-tissue sarcomas.

Pediatric soft-tissue sarcomas represent a relatively common problem in pediatric oncology. The evaluation of these lesions has contributed significantly to the understanding of the molecular basis of sarcomas, and the adjuvant treatment of these tumors has resulted in improved local control and significant improvements in long-term survival. The essence of successful treatment involves preoperative imaging, followed by needle biopsy, preoperative neoadjuvant chemotherapy, and well-documented surgical resection. Indications for radiation therapy and the adequacy of surgical margins remain areas of further investigation. The identification and treatment of well-defined histologic and molecular subtypes will allow further improvements in treatment decisions and clinical results.

Child↗
PubMed1994

Phase II study of liposomal muramyl tripeptide phosphatidylethanolamine (MTP/PE) in advanced soft tissue sarcomas of the adult. An EORTC Soft Tissue and Bone Sarcoma Group study.

The EORTC Soft Tissue and Bone Sarcoma Group conducted a phase II study with intravenous muramyl tripeptide phosphatidylethanolamine (MTP/PE) at a dose of 4 mg once weekly in 20 patients with metastatic soft tissue sarcomas. Responses were not seen in 19 evaluable patients. Toxicity consisted mainly of a mild flu-like syndrome after 62% of drug administrations. It is concluded that MTP/PE at this dose and schedule has no activity in metastatic soft tissue sarcoma.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1986

[Role of chemotherapy in the treatment of soft tissue sarcoma in adults].

Soft tissue sarcomas of adults represent an heterogeneous group of rare malignant tumors, for which clinical and histopathological prognostic factors are now well defined. The GTNM classification recommended by the UICC is effectively predictive for the metastatic potential of these diseases. Although chemotherapy still have limits in advanced sarcomas, the efficacy level reached allows to consider its use with a curative intend, in multidisciplinary therapeutic program. A critical analysis of the studies already published shows that adjuvant chemotherapy can reduce the distant metastases rate in patients presenting an operable primary tumor. Furthermore, the preliminary results of a study indicate that neoadjuvant (induction) chemotherapy may be of value for primarily inoperable patients. All these encouraging results remain to be confirmed by further studies with a long-term follow up of the patients.

Adult↗
PubMed1998

Anterior compartment resection of the thigh in soft-tissue sarcomas.

AIMS: Soft-tissue sarcomas of the anterior thigh present technical problems due to the proximity of the femoral vessels, and the disability caused by a standard anterior compartment resection. METHODS: We treated 44 consecutive patients with primary sarcomas in the anterior thigh with wide resection (n = 15), and modified (n = 26) or standard (n = 3) compartment resection. No patient had amputation as primary treatment. RESULTS: The overall rate of local recurrence was 6/44 (14%). Local recurrence was observed in 1/3 patients with standard anterior compartment resection and 5/41 (12%) of those with wide excision or modified compartment resection. It was noted in 1/6 (17%) patients with adjuvant radiation and 5/38 (13%) of those treated with surgery alone. One of six patients with local recurrence required amputation. The 5-year survival rate was 66% varying significantly according to grade. CONCLUSIONS: Limb preservation was possible in 98% of patients. Wide resection or modified compartment resection was feasible in the majority (93%) of patients resulting in improved function.

Adult↗
PubMed1990

Treatment planning and delivery in neutron radiotherapy of soft tissue sarcomas.

Well differentiated soft tissue sarcomas may benefit from fast neutron radiotherapy, in particular inoperable and recurrent tumors and tumors with residual disease after non-radical surgery. Treatment planning in a multidisciplinary pretherapeutic approach has to be based on tumor size and site and histopathology. Target volume definitions for potential microscopic spread and for the high risk region of local recurrence have to consider the preoperative tumor localization (imaging), the biological behavior and the extent of surgery. GI/II, T1-3 tumors after intralesional or marginal resection are indications for neutron therapy. Treatment planning and delivery has to take into account the narrow therapeutic range of fast neutrons and include individual immobilization devices, manufacturing of bolus and CT based computed dose calculations. Neutron radiotherapy techniques at the d, T generator are comparable to photon techniques except individual beam shaping, field size and portal verification. Total dose is 16 Gy neutrons in the high risk region and 12 to 13 Gy in the region of potential microscopic spread.

Combined Modality Therapy↗
PubMed2002

High-dose chemotherapy in soft tissue sarcoma in children.

Soft tissue sarcomas (STS) are highly malignant tumours that constitute 5-6% of all malignant childhood neoplasms. Of these, rhabdomyosarcoma (RMS) is the most common in children, and has a characteristic two-peak age incidence, 2-5 and 15-19 years. Most children with RMS are cured with conventional chemotherapy and local therapy (surgery with or without radiotherapy). Children with metastatic disease at presentation, particularly those older than 10 years or with bone marrow or bone involvement have a much poorer outcome. In this subgroup, high-dose therapy with stem cell rescue has been studied over the last two decades. Various single or multiagent chemotherapy regimens with or without radiotherapy and autologous stem cell rescue have been used as consolidation treatment with little success. Recent trials using sequential high-dose chemotherapy in the early phase of treatment have proved to be feasible, but the beneficial effect has to be confirmed. The role of purging remains unclear. Collaboration between different international groups is urgently required, in an attempt to improve the poor outcome of children with high risk STS.

Antineoplastic Agents↗