Multiple primary soft tissue sarcomas

BACKGROUND: The synchronous or metachronous development of multiple primary soft tissue sarcomas (STS) of different histopathology has been reported only in isolated case reports. METHODS: The records of patients who developed multiple primary STS and who were treated at a tertiary cancer center between 1982 and 2003 were reviewed. RESULTS: Nine patients with multiple primary STS were identified, representing 0.2% of all patients who were treated for STS. The median age of patients at the time of initial presentation with sarcoma was 60 years (range, 51-81 years). Most patients in this series (n = 7) had metachronous development of a second primary STS. The incidence of second primary sarcomas in patients who were diagnosed previously with STS (4.0 per 10,000 population per year) was significantly greater than the incidence of primary STS in the general population (3.2 per 100,000 population per year; P < 0.01). CONCLUSIONS: Although it is an uncommon occurrence, patients who have a history of STS are at an increased risk for the development of a second primary STS.     

Primary intracranial malignant peripheral nerve sheath tumour responding to chemotherapy

Malignant peripheral nerve sheath tumours (MPNST) are a rare variety of soft tissue sarcomas (STS) arising from major peripheral nerve branches and typically located in the lower extremity, chest wall or the retroperitoneum. It is a biologically aggressive neoplasm for which the treatment of choice is surgery, but usually requires a multimodality approach, having been generally labelled as chemoresistant. We present a case of MPNST located intracranially with a good response to chemotherapy.     

Targeted therapy of soft tissue sarcomas

Soft tissue sarcomas (STS) are rare mesenchymal cancers with a heterogeneous histology. In terms of oncogenesis, sarcomas may be differentiated into diseases with defined molecular events and sarcomas presenting with complex karyotypes lacking identifiable specific genetic changes or expression profile signatures. The former subtype is amenable to therapy with targeted drugs, especially if the tumor carries a consistent causal mutation occurring early in the disease development. While targeted therapy based on tyrosine kinase inhibition such as imatinib and second generation tyrosine kinase inhibitors plays an important role in the treatment of gastrointestinal stromal tumors (GIST), some progress was also achieved in non-GIST sarcomas. Targeting the PI3 kinase/Akt pathway has been shown to be clinically promising in a diversity of different sarcoma subtypes, and inhibition of the vascular endothelial growth factor (VEGF)/VEGF receptor pathway is of special interest in vascular sarcoma subtypes. MDM2 and p53 seem to be interesting targets for STS, but their role has yet to be defined in further clinical trials. Modification of epigenetic mechanisms, especially deacetylation, might be crucial in other STS subtypes such as translocation-associated entities, but its role has yet to be clinically confirmed. Inclusion of patients in controlled clinical trials combined with a translational research platform is critical for further progress.     

Pathological evaluation of soft tissue sarcoma for diagnosis, prognosis and treatment

Soft tissue sarcomas (STS) are rare and heterogeneous group of tumors which differ widely in their clinicopathological features, and have a wide spectrum of clinical course, ranging from indolent tumors with a good prognosis to highly aggressive tumors with a poor prognosis. The diagnostic process of STS is complex and may necessitate an array of ancillary studies, including immunohistochemistry, electron microscopy and molecular genetic methods. Although an ongoing and improved histopathological definition of individual tumor types has been established, there still remains a subset of mesenchymal tumors which are currently not readily classifiable. This review summarizes our experience and that of others in the approach to the pathological evaluation of STS, and especially emphasizes the need to use emerging molecular techniques that can provide important clues for diagnosis, prognosis, and treatment of STS.     

软组织肉瘤的放射治疗

软组织肉瘤(soft tissue sarcomas,STS) 是起源于结缔组织的软组织恶性肿瘤,具有多种不同类型。手术是 STS 主要治疗方法,放疗也是其重要的治疗方式并且是综合治疗早期选择之一。对 STS 进行放疗已经超过 50 年历史,术前和术后放疗对于局部控制都有疗效,只是不良反应不同。软组织肉瘤放疗技术包括远距离放疗(适形放疗、调强放疗、立体定向放疗等) 、近距离放疗(组织间插植放疗、腔内后装放疗、术中放疗等) 等。放疗技术的进步,提高了放疗的精准性和确定性,降低了对病灶周围正常组织的损伤。本文主要针对 STS 放疗技术以及适用原则进行综述。      

Gemcitabine in the treatment of soft tissue sarcomas

Soft tissue sarcomas (STS) are rare mesenchymal tumors with poor prognosis once they present as advanced or metastasized disease. Only few cytostatic drugs have been proven to be active in sarcoma patients and there is a clear need for further treatment options in patients with tumors refractory to standard chemotherapy. Gemcitabine, a nucleoside analogue, has shown activity in several epithelial tumors. Clinical data on the activity of gemcitabine in STS, however, are scarce and heterogeneous. In trials including all subtypes of sarcomas response rates observed with single and multiagent schedules are ranging from 3 to 53%. Histopathological subtypes which seem to exhibit an increased susceptibility to gemcitabine are uterine leiomyosarcomas and angiosarcomas. The synergistic role of other cytostatic drugs, e.g. the role of taxanes, still remains unclear and warrants further trials. We here review the available literature on gemcitabine in the treatment of STS.     

Screening populations at high risk for soft tissue sarcoma and surveillance following soft tissue sarcoma resection

Soft tissue sarcomas (STS) are a rare and diverse group of tumors that affect both adult and pediatric populations. This review discusses current screening recommendations for populations at increased risk for STS, including those with genetic predispositions. We also review surveillance guidelines for those at risk for recurrence following curative-intent surgery.     

Abdominal soft tissue sarcoma: a multicenter retrospective study

Background  

Soft tissue sarcomas (STS) are rare mesenchymal neoplasms with a variety of histological subtypes. However, in Japan, data on the clinical characteristics and prognostic profiles of these tumors are lacking. The purpose of the present study was to clarify the clinical features and outcomes of Japanese patients with retroperitoneal and abdominal STS.     

Soft-tissue sarcoma in adults: An update on the current state of histiotype-specific management in an era of personalized medicine

Soft-tissue sarcomas (STS) are rare tumors that account for 1% of all adult malignancies, with over 100 different histologic subtypes occurring predominately in the trunk, extremity, and retroperitoneum. This low incidence is further complicated by their variable presentation, behavior, and long-term outcomes, which emphasize the importance of centralized care in specialized centers with a multidisciplinary team approach. In the last decade, there has been an effort to improve the quality of care for patients with STS based on anatomic site and histology, and multiple ongoing clinical trials are focusing on tailoring therapy to histologic subtype. This report summarizes the latest evidence guiding the histiotype-specific management of extremity/truncal and retroperitoneal STS with regard to surgery, radiation, and chemotherapy.     

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.     

Expression of multidrug resistance proteins,P-gp,MRP1 and LRP,in soft tissue sarcomas analysed according to their histological type and grade

The biological behaviour of different histological types and grades of soft tissue sarcomas (STS) varies. This might result in a differing sensitivity to cytotoxic drugs. Cross-resistance to functionally and structurally distinct natural-product drugs, known as multidrug resistance (MDR), is associated with the overexpression of P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and lung resistance-related protein (LRP). The purpose of this study was to evaluate the expression of P-gp, MRP1 and LRP in STS according to their histological type and grade. In 141 chemotherapy-naive STS patients, the expression of the three MDR proteins was detected by immunohistochemistry. Nine histological types were documented. These were 19% grade 1, 34% grade 2 and 47% grade 3 tumours. Expression of P-gp and LRP was observed more frequently than the expression of MRP1 (P<0.0001). P-gp expression was most pronounced in malignant fibrous histiocytoma (MFH), but was low in leiomyosarcomas. MRP1 was expressed in most malignant peripheral nerve sheath tumours (MPNST). LRP was strongly expressed in MFH and unspecified sarcomas, but was low in liposarcomas. MRP1 and LRP expression was significantly more common in grades 2 and 3 compared with grade 1 tumours. P-gp expression was correlated with MRP1, especially in grade 3 STS. In conclusion, P-gp, MRP1 and LRP are expressed in the majority of STS, but this expression varies according to the histological type. MRP1 and LRP, but not P-gp expression, were found to be correlated to tumour grade. MDR might contribute to the observed differences in clinical behaviour within the heterogeneous group of STS.     

Oncolytic adenovirus and doxorubicin‐based chemotherapy results in synergistic antitumor activity against soft‐tissue sarcoma

Despite originating from several different tissues, soft‐tissue sarcomas (STS) are often grouped together as they share mesenchymal origin and treatment guidelines. Also, with some exceptions, a common denominator is that when the tumor cannot be cured with surgery, the efficacy of current therapies is poor and new treatment modalities are thus needed. We have studied the combination of a capsid‐modified oncolytic adenovirus CGTG‐102 (Ad5/3‐D24‐GMCSF) with doxorubicin, with or without ifosfamide, the preferred first‐line chemotherapeutic options for most types of STS. We show that CGTG‐102 and doxorubicin plus ifosfamide together are able to increase cell killing of Syrian hamster STS cells over single agents, as well as upregulate immunogenic cell death markers. When tested in vivo against established STS tumors in fully immunocompetent Syrian hamsters, the combination was highly effective. CGTG‐102 and doxorubicin (without ifosfamide) resulted in synergistic antitumor efficacy against human STS xenografts in comparison with single agent treatments. Doxorubicin increased adenoviral replication in human and hamster STS cells, potentially contributing to the observed therapeutic synergy. In conclusion, the preclinical data generated here support clinical translation of the combination of CGTG‐102 and doxorubicin, or doxorubicin plus ifosfamide, for the treatment of STS, and provide clues on the mechanisms of synergy.     

Clinical outcome of patients with previously untreated soft tissue sarcomas in relation to tumor grade,DNA ploidy and karyotype

The most important prognostic factor in soft tissue sarcomas (STS) is tumor grade. Since most grading methods are subject to the interpretation of the individual pathologist, there is a need for objective criteria such as DNA ploidy and karyotype, which are of prognostic value in several types of malignancy. We have analyzed the relationships among tumor grade, DNA ploidy, cytogenetic abnormalities and the clinical outcome of 44 previously untreated patients with 12 different histological types of primary STS. The tumors were graded according to the method of Coindre, which resulted in 9 grade I (20%), 18 grade II (41%) and 17 grade III (39%) STS. DNA flow cytometry and chromosomal analysis were performed using standard techniques. After a median follow-up time of 39 (range, 2–124) months, Kaplan-Meier survival analysis was performed. Significant differences in 5-year overall survival were found between patients with grade I or II and grade III STS (p < 0.05). Seventeen STS were aneuploid and 26 were euploid. In 21 of 39 successfully cultured STS an abnormal karyotype was found. There were no significant differences in survival in relation to DNA ploidy or the presence of chromosomal abnormalities. Our results show that grading had higher prognostic value than DNA ploidy or the presence of cytogenetic abnormalities in this heterogeneous group of STS. Int. J. Cancer 74:396–402, 1997. © 1997 Wiley-Liss, Inc.     

A robust assay for alternative lengthening of telomeres in tumors shows the significance of alternative lengthening of telomeres in sarcomas and astrocytomas.

PURPOSE AND EXPERIMENTAL DESIGN: Telomeres of tumor cells may be maintained by telomerase or by alternative lengthening of telomeres (ALT). The standard ALT assay requires Southern analysis of high molecular weight genomic DNA. We aimed to establish and validate an ALT assay suitable for archived paraffin-embedded tumors and to use it to examine the prevalence and clinical significance of ALT in various types of tumors that are often telomerase negative. RESULTS: To assay for ALT, we detected ALT-associated promyelocytic leukemia (PML) bodies (APBs) by combined PML immunofluorescence and telomere fluorescence in situ hybridization. APBs are PML nuclear domains containing telomeric DNA and are a known hallmark of ALT in cell lines. The APB assay concurred with the standard ALT assay in 62 of 62 tumors and showed that 35% of 101 soft tissue sarcomas (STS), 47% of 58 osteosarcomas (especially younger patients), 34% of 50 astrocytomas, and 0% of 17 papillary thyroid carcinomas were ALT positive (ALT+). The prevalence of ALT varied greatly among different STS subtypes: malignant fibrous histiocytomas, 77%; leiomyosarcomas, 62%; liposarcomas, 33%; synovial sarcomas, 9%; and rhabdomyosarcomas, 6%. ALT correlated with survival in glioblastoma multiforme and occurred more often in lower-grade astrocytomas, but ALT+ and ALT- sarcomas were equally aggressive in terms of grade and clinical outcome. CONCLUSION: The APB assay for ALT is suitable for paraffin-embedded tumors. It showed that a substantial proportion of STS, osteosarcomas, and astrocytomas, but not papillary thyroid carcinomas use ALT. APB positivity correlated strongly with survival of patients with astrocytomas.     

Appraising the current role of chemotherapy for the treatment of sarcoma

Sarcomas are a heterogeneous group of relatively rare mesenchymal neoplasms. They can be grouped into two general categories: soft tissue sarcoma (STS) and primary bone sarcoma, which are treated differently. Because sarcomas are relatively rare and complex with a wide variety of different histopathologic subtypes, evaluation by multidisciplinary teams who have expertise in the field is recommended. Treatment guidelines for the use of chemotherapy in patients with STS and bone sarcoma have been published by the National Comprehensive Cancer Network. The role of adjuvant chemotherapy in resected STS remains controversial. Although chemotherapy improves disease-free survival, the long-term overall survival benefit remains unproven. Chemotherapy is typically used as palliative treatment for most subtypes of metastatic STS. In contrast, chemotherapy has a proven role in the treatment of primary bone tumors and Ewing sarcoma, but it has not demonstrated efficacy in the treatment of chondrosarcoma. The standard chemotherapy regimens used in sarcoma are associated with significant toxicity, including long-term complications. Less intense and less toxic regimens are the focus of ongoing clinical research. Newer cytotoxic agents with an improved safety profile, such as trabectedin and palifosfamide, are currently in development. Future research needs to focus on identification of subpopulations of patients that are most likely to benefit from chemotherapy.     

Soft tissue sarcoma--compliance with guidelines

BACKGROUND: Because soft tissue sarcomas (STS) are rare, guidelines for the diagnosis and treatment of patients with STS were developed. Because the diagnostic management is essential for definitive treatment, adherence to these guidelines is important. METHODS: Primary STS registered by the Comprehensive Cancer Center North-Netherlands from January 1989 to January 1996 were analyzed retrospectively with regard to adherence to the diagnostic guidelines. Urogenital, gastrointestinal STS, and Kaposi sarcomas were excluded. RESULTS: Three hundred fifty-one STS patients were analyzed. In the specialized center, 69% of patients were age < 60 years, whereas, in district hospitals, 63% of patients were age > 60 years. With increased age, referral to the center declined in a linear fashion. For all guidelines, adherence was significantly better in the center. In district hospitals, patient volume had no significant influence on compliance with the guidelines, except for the management of patients with STS > or = 3 cm. In district hospitals, where fewer than 15 patients were treated in the 7-year period, significantly more often, an inadequate biopsy or even no biopsy procedure was performed prior to resection. CONCLUSIONS: In many aspects of the diagnostic process of STS, existing guidelines were not followed, especially in community hospitals. Adherence to all individual guidelines was significantly better in the specialized center. To improve compliance with future STS guidelines, appropriate guideline development, dissemination, and implementation programs should be developed. Concentration of patients with STS in a limited number of hospitals and intensified collaboration with specialized centers seem advisable. Special attention should be paid to older patients, who significantly more often were not referred to a specialized center.     

Expression of HER1/EGFR protein in human soft tissue sarcomas.

AIM: To measure epidermal growth factor receptor (HER1/EGFR) expression in a range of soft tissue sarcoma (STS) patient samples. METHOD: HER1/EGFR expression was examined by immunohistochemistry in archival tissues of 46 STS patients. RESULTS: HER1/EGFR was positively expressed in 36/46 of STS samples distributed among different histological types. The levels of HER1/EGFR in STS tumour tissues in positive samples were higher compared to those in nearby normal tissues. CONCLUSION: HER1/EGFR is significantly expressed in soft tissue sarcomas, which is a finding reflected in other series. The significance of this finding for targeted therapy is as yet unknown.     

Sarcomas of the fallopian tube: disentangling a rare entity

Sarcomas of the fallopian tube are exceedingly rare malignancies. They have been considered the most lethal of all gynaecological malignancies with high metastatic potential, frequent recurrences and cancer-related deaths. The reported pathological types of the fallopian tube sarcomas are malignant mixed mullerian (mesodermal) tumours or carcinosarcomas, leiomyosarcomas, rhabdomyosarcomas, liposarcomas, and synovial sarcomas. The rarity of these sarcomas and their often aggressive clinical course has resulted in a relatively limited amount of literature. Thus a single hospital or specialist cannot gain sufficient experience with these tumours. This review article tries to elucidate this uncommon malignancy, in a systematic way, focusing on the different pathological types, epidemiology, risk factors, diagnosis, survival, and different therapeutic modalities (surgery, chemotherapy, and radiotherapy).     

Soft tissue sarcoma as a second malignant neoplasm in the pediatric age group

BACKGROUND: Survivors of childhood malignancies have an increased risk of developing second malignant neoplasms (SMN) due to their prior treatment and/or genetic susceptibility. A small proportion of SMNs are soft tissue sarcomas (STS), whose prognosis is generally thought to be poor, though publications on such patients' treatment and outcome is limited. METHODS: The authors analyzed 25 patients who were registered for the Italian Cooperative Group protocols for pediatric STS from 1979 to 2000. The primary tumor was STS in five patients; Hodgkin disease in five patients; leukemia in four patients; retinoblastoma, neuroblastoma, and Wilms tumor in two patients each; and other tumor types in five patients. SMNs occurred after a median of 8 years (range, 1.9-15.0 years) and included rhabdomyosarcoma (RMS) in 4 patients, malignant peripheral nerve sheath tumor in 4 patients, extraosseous Ewing family tumor (EFT) in 4 patients, leiomyosarcoma in 3 patients, fibrosarcoma in 2 patients, synovial sarcoma in 2 patients, and other tumor types in 6 patients. Treatment generally was administered according to the guidelines for primary STS. RESULTS: Seven non-RMS patients with STS underwent surgery alone, whereas 18 patients received chemotherapy and 8 patients received radiotherapy. Retreatment was feasible with acceptable toxicity. Fifteen patients were alive in complete remission of their SMN at the time of last follow-up. Responses to chemotherapy and survival were satisfactory for patients with tumors such as RMS and EFT. Complete tumor resection was correlated with a favorable prognosis in patients with other types of STS and in patients with postirradiation sarcoma. Two patients developed a third malignancy. CONCLUSIONS: Although prior treatment may hinder the management of these patients, pediatric STS second malignancies can be cured using the same strategies used for de novo pediatric sarcomas. Long-term follow-up is mandatory given the risks of further malignancies and more severe, treatment-related side effects.