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Soft Tissue Sarcomas

Soft tissue sarcomas are malignant tumours that may arise in any of the mesodermal tissues (muscles, tendons, vessels that carry blood or lymph, joints, and fat). Sarcomas are a diverse range of tumours, they are named after the type of soft tissue cell they arise from. Types of soft tissue sarcomas include; alveolar soft-part sarcoma, angiosarcoma, fibrosarcoma, leiomyosarcoma, liposarcoma, malignant fibrous histiocytoma, hemangiopericytoma, mesenchymoma, schwannoma, peripheral neuroectodermal tumours, rhabdomyosarcoma, synovial sarcoma, and other types. In terms of treatment these different sub-types are usually treated in the same way using a uniform soft tissue protocol.

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Information for Patients and the Public
Information for Health Professionals / Researchers
Latest Research Publications
Childhood Soft Tissue Sarcoma
Uterine Sarcoma
Kaposi Sarcoma
Gastrointestinal Stromal Tumors

Information Patients and the Public (16 links)

Information for Health Professionals / Researchers (19 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Jeong JY, Kim SY, Jeong DC, Kim KJ
A small Askin's tumor presenting with early onset of chest pain.
World J Surg Oncol. 2015; 13:112 [PubMed] Free Access to Full Article Related Publications
Most primitive neuroectodermal tumor of the chest wall destroy the rib, chest wall muscles, diaphragm, and lung or extend into the spinal compartment, resulting in a large-sized tumor and symptoms. In contrast, we recently encountered a rare case of Askin's tumor presenting with early-onset chest pain despite the small size. After resection of the tumor and adjuvant chemotherapy, the patient remains disease-free over 3 years of follow-up.

Di Luigi G, D'Alfonso A, Patacchiola F, et al.
Leiomyosarcoma: a rare malignant transformation of a uterine leiomyoma.
Eur J Gynaecol Oncol. 2015; 36(1):84-7 [PubMed] Related Publications
The malignant transformation of a uterine leiomyoma is still debated and, if it occurs, it is very rare. The case of a patient affected by one small leiomyoma is described. Diagnosis was made postoperatively on histopathological examination. The case reported here is meant to underline the need to keep all uterine myomas in check since the transition into leiomyosarcomas (LMSs) may occur with an evolution over a time period which has not been established so far. Specific receptors for luteinizing hormone/human chorionic gonadotropin (LH/hCG) have also been identified in the myometrium of several animal species, including humans. Conventional LMSs express estrogen receptors (ER), progesterone receptors (PR), and androgen receptors (AR) in 30-40% of cases. In comparison with other more common uterine malignancies, uterine LMSs bear some resemblance to type 2 endometrial carcinomas and high-grade serous carcinomas of ovary/fallopian tube origin, based on their genetic instability, frequent p53 abnormalities, aggressive behavior, and resistance to chemotherapy. It could be useful to understand with further researches if hormonal stimulation could be a contributing factor of uterine leiomyoma transformation into LMS. Until today the oncogenic mechanisms underlying the development of uterine LMSs remain elusive.

Kerimoglu OS, Pekin A, Yilmaz SA, et al.
Pyometra in elderly post-menopausal women: a sign of malignity.
Eur J Gynaecol Oncol. 2015; 36(1):59-61 [PubMed] Related Publications
PURPOSE: To describe the clinical and histopathological characteristics of 12 patients with pyometra and highlight the increased incidence of gynecological malignancy in these patients.
MATERIALS AND METHODS: The authors examined the medical records of 12 patients with pyometra, who were treated between 2009 and 2013.
RESULTS: All patients were post-menopausal, and their mean age was 70.83 ± 6.978 years (min = 61, max = 82). To remove purulent fluid via dilation and because of the probability of malignancy, three patients (25%) underwent cervical biopsy and endometrial curettage; the other nine patients (75%) underwent curettage alone, with suitable antibiotic therapy. Of the 12 patients, nine (75%) had gynecologic malignancy [(endometrial cancer, n = 5, 41.6%), (cervical cancer, n = 3, 25%), (uterine leiomyosarcoma, n = 1, 8.3%)]. In three (25%) patients, the cause of pyometra was benign pathologies, among which the most common were leiomyomas (n = 2, 66.6%).
CONCLUSION: Pyometra diagnosed during the post-menopausal period should be considered a complication caused by gynecological malignancy until proven otherwise.

Zendah I, Habibech S, Kwas H, et al.
Primary sarcomatoid lung cancer: clinical and evolutive features: about five cases.
Tunis Med. 2014; 92(11):678-80 [PubMed] Related Publications
BACKGROUND: Primary sarcomatoid carcinoma of the lung are rare non small cell lung cancers (NSCLC) recently individualized by the World Health Organization. Their clinical, radiological and evolutive features are not well known but they seem to have bad prognosis with rapid progression and early metastases. Although they are felt to be chemo-refractory they must be treated as the other subtypes of NSCLC.
AIM: To evaluate clinical, radiological and evolutive features of primary sarcomatoid carcinoma of the lung.
METHODS: We report the cases of five patients presenting sarcomatoid carcinomas and assess their clinical and evolutive data.
RESULTS: One patient had stage IIB cancer underwent surgical resection and adjuvant chemotherapy, he is alive 18 months later; another had stage IIIB was treated by radio and chemotherapy and is alive 6 months later; and three other patients had stage IV in whom one had chemotherapy, the two others did not because of they had performance status. They died 1 to 3 months after the diagnosis.
CONCLUSION: Lung sarcomatoid carcinomas are of bad prognosis. Their treatment is nowadays not well established. Much more good studies are therefore needed.

Belfiore MP, Ronza FM, Della Volpe T, et al.
Long-term local disease control in a recurrent soft-tissue sarcoma of the thigh treated by radiofrequency ablation.
J Surg Oncol. 2015; 111(6):708-10 [PubMed] Related Publications
In 2008, we performed radiofrequency ablation (RFA) in an elderly patient with a large recurrent soft-tissue sarcoma of the thigh, previously treated with surgery and radiotherapy. After ablation, a marked shrinkage of tumor was obtained. Further local recurrences occurred during follow-up, all safely treated by RFA, with local control of the disease maintained until 6-year follow-up. RFA was safe, effective, and repeatable for soft-tissue sarcoma recurrences, and allowed long-term local control of the disease.

Lee DF, Su J, Kim HS, et al.
Modeling familial cancer with induced pluripotent stem cells.
Cell. 2015; 161(2):240-54 [PubMed] Article available free on PMC after 09/04/2016 Related Publications
In vitro modeling of human disease has recently become feasible with induced pluripotent stem cell (iPSC) technology. Here, we established patient-derived iPSCs from a Li-Fraumeni syndrome (LFS) family and investigated the role of mutant p53 in the development of osteosarcoma (OS). LFS iPSC-derived osteoblasts (OBs) recapitulated OS features including defective osteoblastic differentiation as well as tumorigenic ability. Systematic analyses revealed that the expression of genes enriched in LFS-derived OBs strongly correlated with decreased time to tumor recurrence and poor patient survival. Furthermore, LFS OBs exhibited impaired upregulation of the imprinted gene H19 during osteogenesis. Restoration of H19 expression in LFS OBs facilitated osteoblastic differentiation and repressed tumorigenic potential. By integrating human imprinted gene network (IGN) into functional genomic analyses, we found that H19 mediates suppression of LFS-associated OS through the IGN component DECORIN (DCN). In summary, these findings demonstrate the feasibility of studying inherited human cancer syndromes with iPSCs.

Gilani S, Al-Khafaji B
Dermatofibrosarcoma protuberans of the vulva: a mesenchymal tumour with a broad differential diagnosis and review of literature.
Pathologica. 2014; 106(4):338-41 [PubMed] Related Publications
Dermatofibrosarcoma protuberans (DFSP) is a malignant cutaneous soft tissue tumour, which rarely presents in the vulva. We report an unusual case of this tumour involving the vulva. A 61-year-old female presented with a mass in the left mons pubis. Subsequent excisional biopsy of the mass was performed. Histologic evaluation of the specimen showed a spindle cell lesion consisting of fibroblast-like cells arranged in a storiform pattern. On average, there were 2 to 3 mitotic figures per 10 high power field (hpf). The neoplastic cells showed extension into the surrounding fibroadipose tissue. A panel of immunohistochemical stains including CD34, S-100, melan-A, HMB-45, vimentin and smooth muscle actin (SMA) were tested. The neoplastic cells showed diffuse staining with CD34 and vimentin, while the rest were negative. Based on the morphologic and immunohistochemical staining pattern, a diagnosis of DFSP was rendered. The patient underwent two subsequent resections before she had clear resection margins. The postoperative course was unremarkable. The patient is disease free without recurrence after a follow-up of 12 months. DFSP infrequently involves the vulva and should be considered in the differential diagnosis of other spindle cell lesions presenting in this unusual site. The role of immunohistochemical staining with CD34 is imperative in establishing the diagnosis. The rate of local reoccurrence is high, but it rarely shows metastasis. Treatment of choice is wide local surgical excision with close follow-up to detect reoccur- rence.

Mlika M, Berraies A, Boudaya MS, et al.
Primary mediastinal angiosarcoma: a rare observation in a patient with 8-year-survival.
Pathologica. 2014; 106(4):335-7 [PubMed] Related Publications
BACKGROUND: Vascular tumours of the mediastinum are rare, accounting for 1-2% of all mediastinal tumours in this location. Angiosarcomas are most often encountered as sporadic lesions, typically in the scalp or face of elderly patients. However, they can occur in any anatomic site. Mediastinal angiosarcomas (MA) are very rare with less than 50 cases reported.
CASE REPORT: The authors describe the case of a 38-year-old woman whose past medical history was consistent for a MA that was diagnosed in 2003. This tumour was treated by complete surgical resection followed by radiation therapy and chemotherapy. Diagnosis was based on histologic examination. In 2011, the patient presented a pleural localisation of the angiosarcoma and died one month after admission, 8 years after diagnosis of the MA.
CONCLUSION: MA is a very rare tumour causing a diagnostic dilemma. Clinical and radiologic findings are non-specific, and final diagnosis is based on histologic examination. The case described is unusual considering the long period of survival, which may be explained by the treatment modalities associating complete surgical resection, chemotherapy and radiation therapy.

Filotico M, Damuri A, Filotico R
A peculiar fibroma-like lesion of superficial soft tissue: morphologic and immunophenotypic evaluation.
Pathologica. 2014; 106(4):327-9 [PubMed] Related Publications
Apeculiar lesion of superficial soft tissue characterised by fibroma-like morphology and an immunohistochemical profile consisting of CK+, VIM+, CD34+, CD31+/-, FLI1+ and INI-1 retained is described. The lesion entered into differential diagnosis with the so-called fibroma-like variant of epithelioid sarcoma, with the entities defined as ES-like/pseudomyogenic haemangioendothelioma and the recently identified entity defined as superficial CD34+ fibroblastic tumour. All of these entities share a common morphological structure, but differ in their immunophenotypic profile.

Magro G, Salvatorelli L, Angelico G, et al.
Lipomatous angiomyofibroblastoma of the vulva: diagnostic and histogenetic considerations.
Pathologica. 2014; 106(4):322-6 [PubMed] Related Publications
We report a rare case of angiomyofibroblastoma (AMFB) of the vulva, composed predominantly of a mature fatty component, representing approximately 60% of the entire tumour. The tumour, designated as "lipomatous AMFB", should be interpreted as the morphological result of an unbalanced bidirectional differentiation of the presumptive precursor stromal cell resident in the hormonally-responsive stroma of the lower genital tract, with the adipocytic component overwhelming the fibroblastic/myofibroblastic one. The close admixture of adipocytes with spindled/epithelioid cells of the conventional AMFB resulted, focally, in a pseudo-infiltrative growth pattern and pseudo-lipoblast-like appearance, raising problems in differential diagnosis, especially with well-differentiated lipoma-like liposarcoma and spindle cell liposarcoma. Awareness of the possibility that vulvo-vaginal AMFB may contain large amount of lipomatous component is crucial to avoid confusion with other bland-looking spindle cell tumours containing infiltrating fat.

Dai L, Chen Y, Toole B, et al.
Induction of hyaluronan production by oncogenic KSHV and the contribution to viral pathogenesis in AIDS patients.
Cancer Lett. 2015; 362(2):158-66 [PubMed] Article available free on PMC after 01/07/2016 Related Publications
Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent for Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL), malignancies arising primarily in immunocompromised patients particularly AIDS-patients, which still lack effective therapy. Hyaluronan (HA) is a large glucuronic acid and has been found closely related to multiple functions in cancer cells, although its role in viral oncogenesis remains largely unknown. Here we provide first evidence that KSHV de novo infection induces HA production from primary endothelial cells through upregulation of HA synthase gene 1 (Has1) and a multifunctional glycoprotein, CD147. Further data demonstrate that KSHV-induced HA production requires viral latent protein, LANA (in particular functional domain A) and MAPK/ERK signaling activities. In functions, HA production is necessary for KSHV/LANA-induced primary endothelial cell invasion, a hallmark feature for KS development. For clinical relevance, our data indicate that the KSHV+ group has higher levels of HA and Has1 activities in its plasma than the KSHV- group of cohort HIV-infected patients. Together, our findings provide innovative insights into the mechanisms of oncogenic virus activation of HA production and its role in virus-associated malignancy pathogenesis, which may help to develop novel therapeutic strategies by targeting HA and related signaling.

Shakeel-u-Rehman, Rah B, Lone SH, et al.
Design and Synthesis of Antitumor Heck-Coupled Sclareol Analogues: Modulation of BH3 Family Members by SS-12 in Autophagy and Apoptotic Cell Death.
J Med Chem. 2015; 58(8):3432-44 [PubMed] Related Publications
Sclareol, a promising anticancer labdane diterpene, was isolated from Salvia sclarea. Keeping the basic stereochemistry-rich framework of the molecule intact, a method for the synthesis of novel sclareol analogues was designed using palladium(II)-catalyzed oxidative Heck coupling reaction in order to study their structure-activity relationship. Both sclareol and its derivatives showed an interesting cytotoxicity profile, with 15-(4-fluorophenyl)sclareol (SS-12) as the most potent analogue, having IC50 = 0.082 μM against PC-3 cells. It was found that SS-12 commonly interacts with Bcl-2 and Beclin 1 BH3 domain proteins and enhances autophagic flux by modulating autophagy-related proteins. Moreover, inhibition of autophagy by autophagy inhibitors protected against SS-12-induced apoptosis. Finally, SS-12 effectively suppressed tumor growth in vivo in Ehrlich's ascitic and solid Sarcoma-180 mouse models.

Imtiaz S, Kazmi A
Patterns of care and outcomes of adult osteosarcoma in a tertiary care cancer centre in Pakistan.
J Pak Med Assoc. 2014; 64(10):1166-70 [PubMed] Related Publications
OBJECTIVE: To present our experience of treatment outcomes in adult osteosarcoma patients.
METHODS: The retrospective study was conducted at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised data related to 74 adult patients with osteosarcoma from 1995 to 2009. The treatment plan consisted of surgery preceded by neo-adjuvant chemotherapy followed by adjuvant chemotherapy. SPSS 16 was used for statistical analysis.
RESULTS: Of the 74 patients in the study, 58 (78%) were in the 18-29 age group with an overall male-to-female ratio of 3:1. The commonest site of disease was femur, 30 (43%). Of the 66 (89%) patients undergoing definitive surgery, 59 (89.4%) had amputation. The remaining 7 (10.6%) limb salvage operations were in the neo-adjuvant chemotherapy group. Good histopathological response rates in high-dose methotrexate containing regimens and other regimens were similar with an overall good response rate of 18/51 (35%). The commonest site of relapse was lung.Twelve out of 27 (44%) patients with lung-only metastases underwent successful metastatectomy. For patients with localised disease at presentation 3-year event-free survival was 30%, and 3-year overall survival was 71%. For patients with metastases at presentation 3-year overall survival was 45%. Median overall survival for patients receiving high-dose methotrexate and other regimens was 1.7 years vs 2.9 years.
CONCLUSION: Adult osteosarcoma treated with cisplatin/doxorubicin based chemotherapy and surgery had good outcomes. The role of high-dose methotrexate in adult osteosarcoma remains uncertain.

Eefsen RL, Vermeulen PB, Christensen IJ, et al.
Growth pattern of colorectal liver metastasis as a marker of recurrence risk.
Clin Exp Metastasis. 2015; 32(4):369-81 [PubMed] Related Publications
Despite improved therapy of advanced colorectal cancer, the median overall survival (OS) is still low. A surgical removal has significantly improved survival, if lesions are entirely removed. The purpose of this retrospective explorative study was to evaluate the prognostic value of histological growth patterns (GP) in chemonaive and patients receiving neo-adjuvant therapy. Two-hundred-fifty-four patients who underwent liver resection of colorectal liver metastases between 2007 and 2011 were included in the study. Clinicopathological data and information on neo-adjuvant treatment were retrieved from patient and pathology records. Histological GP were evaluated and related to recurrence free and OS. Kaplan-Meier curves, log-rank test and Cox regression analysis were used. The 5-year OS was 41.8% (95% CI 33.8-49.8%). Growth pattern evaluation of the largest liver metastasis was possible in 224 cases, with the following distribution: desmoplastic 63 patients (28.1%); pushing 77 patients (34.4%); replacement 28 patients (12.5%); mixed 56 patients (25.0%). The Kaplan-Meier analyses demonstrated that patients resected for liver metastases with desmoplastic growth pattern had a longer recurrence free survival (RFS) than patients resected for non-desmoplastic liver metastases (p=0.05). When patients were stratified according to neo-adjuvant treatment in the multivariate Cox regression model, hazard ratios for RFS compared to desmoplastic were: pushing (HR=1.37, 95% CI 0.93-2.02, p=0.116), replacement (HR=2.16, 95% CI 1.29-3.62, p=0.003) and mixed (HR=1.70, 95% CI 1.12-2.59, p=0.013). This was true for chemonaive patients as well as for patients who received neo-adjuvant treatment.

Yu H, Sun H, Bai Y, et al.
MEF2D overexpression contributes to the progression of osteosarcoma.
Gene. 2015; 563(2):130-5 [PubMed] Related Publications
The underlying molecular pathogenesis of osteosarcoma remains poorly understood. The transcription factor MEF2D promotes the survival of various types of cells and functions as an oncogene in liver cancer. However, its potential contribution to osteosarcoma has not been explored. In this study, we investigated MEF2D expression and function in osteosarcoma, finding that MEF2D elevation in osteosarcoma clinical specimens was associated with patients' poor prognosis. MEF2D suppression was shown to decrease the proliferation of osteosarcoma cells, while forced expression of MEF2D was able to promote the proliferation of normal bone fibroblast. Notably, MEF2D silencing abolished osteosarcoma tumorigenicity in an animal model. Mechanistic investigations revealed that MEF2D silencing triggered G2-M arrest in osteosarcoma cells by suppressing RPRM and CDKN1A. miR-144 was found to suppress the expression of MEF2D in osteosarcoma cells. Collectively, our results demonstrated that MEF2D is a candidate oncogene for osteosarcoma and a potential molecular target for cancer therapy.

Raphael S, Yusuf I, Imam I
Childhood rhabdomyosarcoma in Kano, Nigeria: a retrospective analysis of 52 cases.
Niger J Med. 2015 Jan-Mar; 24(1):32-6 [PubMed] Related Publications
BACKGROUND: Rhabdomyosarcoma is the most common soft tissue sarcoma in children ≤ 15 years of age. There is, however, a paucity of reports on the pattern of its occurrence in Nigeria and other parts of Africa.
OBJECTIVE: The aim of this review is to highlight the age and sex distribution, anatomical location and morphological characteristics of rhabdomyosarcoma among children in Kano, northwestern Nigeria.
PATIENTS AND METHOD: This is a 14 year retrospective study of all cases of rhabdomyosarcomas occurring in children diagnosed at the Pathology Department of Aminu Kano Teaching Hospital, Kano, Nigeria. Clinical data obtained included sex, age, tumour site and histologic subtype.
RESULTS: Fifty two children were seen with a male to female ratio of 1 : 1.3. The ages of these Patients ranged from 4 months to 15 years with a mean (SD) age of 6.99 (4.1) years and peak age frequency in the 0 to 5 years age group. The embryonal variant was the most common histological subtype (69%). The others were alveolar (27%) and pleomorphic (4%) variants. The head and neck was the most affected region (44%) and the most common primary site was the orbit (19.2%).
CONCLUSION: Rhabdomyosarcoma is the most common childhood soft tissue sarcoma in Kano. It occurs in females more frequently than males and the most common histologic subtype is embryonal rhabdomyosarcoma affecting predominantly the orbit.

Chow LT
Primary synovial epithelioid sarcoma of the knee: distinctly unusual location leading to its confusion with pigmented villonodular synovitis.
APMIS. 2015; 123(4):350-8 [PubMed] Related Publications
Epithelioid sarcoma (ES) is a rare malignant soft tissue tumor occurring in the distal extremities of young adults and is characterized histologically by nodules of epithelioid cells showing central necrosis. Intra-articular ES is extremely rare; only four cases have been reported, but their radiologic and histologic documentation of intra-articular origin have been imprecise. We report the first radiologically and histologically well-documented case of primary synovial ES. A 59-year-old woman presented with pain followed by swelling of her right knee for 6 months. MRI revealed an entirely intra-articular nodular synovial mass in the lateral part of the right knee joint in a background of diffusely thickened synovium. Synovectomy was performed under the clinical impression of pigmented villonodular synovitis (PVNS), a diagnosis erroneously confirmed by the reporting pathologist. The tumor rapidly recurred 3 months afterward and the diagnosis of primary synovial ES was made. Despite above-knee amputation, the tumor continued to spread proximally to the retroperitoneum. She developed multiple lung metastases and died 20 months after initial presentation. The nodular aggregates of tumor cells with central necrosis resulted in diffuse polypoid synovial thickening mimicking tuberculous synovitis and PVNS. The tumor cells showed positive staining for EMA, CK19, CD34, and complete loss of INI1 staining, establishing the diagnosis of primary synovial ES. The ES spread from the synovium to and along the joint capsule, and then extra-articularly into the soft tissue surrounding the knee joint, with lymphovascular permeation. Such pattern of spread calls for radical surgical excision as the treatment of choice.

Tang C, Zhao Y, Huang S, et al.
Influence of Artemisia annua extract derivatives on proliferation, apoptosis and metastasis of osteosarcoma cells.
Pak J Pharm Sci. 2015; 28(2 Suppl):773-9 [PubMed] Related Publications
Regarding the Artemisia annua extract derivatives called dihydroarteminin (DHA) as the object, we studied about its influence to the proliferation, apoptosis and metastasis of human osteosarcoma cells. First, we cultured in vitro the osteosarcoma cell strain and divided them into groups, then detected the cell proliferation, apoptosis and cell metastasis, etc by multiple measurement technique. Finally, we observed the influence of DHA to human osteosarcoma cells. Osteosarcoma cells were all sensitive to DHA, and the appropriate concentration range was 10~40μM. DHA could effectively restrain its protein expression, and there was a significant difference between experimental group and control group. These finding suggest that, the Artemisia annua extract derivatives (DHA) has a biological effect of observably restraining the proliferation and metastasis of human osteosarcoma cells and promoting the tumour cell apoptosis.

Meyliker RG, Strauss RA
Periosteal osteosarcoma of the mandible: a case report.
J Oral Maxillofac Surg. 2015; 73(4):787.e1-4 [PubMed] Related Publications
This report describes a rare case of a periosteal osteosarcoma of the mandible in a 50-year-old African-American woman who showed no underlying bony changes at panoramic radiography or computed tomography. This report describes the diagnostic workup used to obtain the definitive diagnosis and the surgical treatment and recommended method for subsequent tumor surveillance. Emphasis is placed on distinguishing periosteal osteosarcomas as a separate entity from conventional intraosseous osteosarcomas in the head and neck region.

Kawai A, Araki N, Sugiura H, et al.
Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma: a randomised, open-label, phase 2 study.
Lancet Oncol. 2015; 16(4):406-16 [PubMed] Related Publications
BACKGROUND: Trabectedin binds to the minor groove of DNA and blocks DNA repair machinery. Preclinical data have shown that trabectedin also modulates the transcription of the oncogenic fusion proteins of translocation-related sarcomas. We aimed to assess the efficacy and safety of trabectedin as second-line therapy or later for patients with advanced translocation-related sarcoma.
METHODS: We did a multicentre randomised open-label study in Japan. Eligible patients had pathological diagnosis of translocation-related sarcoma, were aged 19 years or older, were unresponsive or intolerant to standard chemotherapy regimens, no more than four previous chemotherapy regimens, Eastern Cooperative Oncology Group performance status 0 or 1, adequate bone marrow reserve, renal and liver functions, and had measurable lesions. Patients were randomly assigned (1:1) by the minimisation method to receive either trabectedin (1·2 mg/m(2) given via a central venous line over 24 h on day 1 of a 21 day treatment cycle) or best supportive care, which was adjusted centrally by pathological subtype. Investigators, patients, and the sponsor were unmasked to the treatment assignment. Progression-free survival and objective responses were assessed by a masked central radiology imaging review. Efficacy was assessed by masked central radiology imaging review. The primary endpoint was progression-free survival for the full analysis set population. Follow-up is ongoing for the patients under study treatment. The study is registered with Japan Pharmaceutical Information Center, number JapicCTI-121850.
FINDINGS: Between July 11, 2012, and Jan 20, 2014, 76 patients were enrolled and allocated to receive either trabectedin (n=39) or best supportive care (n=37). After central review to confirm pathological subtypes, 73 patients (37 in the trabectedin group and 36 in the best supportive care group) were included in the primary efficacy analysis. Median progression-free survival of the trabectedin group was 5·6 months (95% CI 4·1-7·5) and the best supportive care group was 0·9 months (0·7-1·0). The hazard ratio (HR) for progression-free survival of trabectedin versus best supportive care was 0·07 (90% CI 0·03-0·14 and 95% CI 0·03-0·16) by a Cox proportional hazards model (p<0·0001). The most common drug-related adverse events for patients treated with trabectedin were nausea (32 [89%] of 36), decreased appetite (21 [58%]), decreased neutrophil count (30 [83%]), increased alanine aminotransferase (24 [67%]), and decreased white blood cell count (20 [56%]).
INTERPRETATION: Trabectedin significantly reduced the risk of disease progression and death in patients with advanced translocation-related sarcoma after standard chemotherapy such as doxorubicin, and should be considered as a new therapeutic treatment option for this patient population.
FUNDING: Taiho Pharmaceutical Co., Ltd.

Pautier P, Floquet A, Chevreau C, et al.
Trabectedin in combination with doxorubicin for first-line treatment of advanced uterine or soft-tissue leiomyosarcoma (LMS-02): a non-randomised, multicentre, phase 2 trial.
Lancet Oncol. 2015; 16(4):457-64 [PubMed] Related Publications
BACKGROUND: Metastatic leiomyosarcomas of uterine or soft-tissue origin have poor prognosis and moderate chemosensitivity. Trabectedin has shown activity in pretreated leiomyosarcoma. We did a single-group, multicentre, phase 2 trial (LMS-02) to assess the effect of first-line doxorubicin and trabectedin combination on disease control and survival.
METHODS: Adults (18 years to physiological age ≤70 years) with measurable metastatic or unresectable uterine leiomyosarcoma or soft-tissue leiomyosarcoma who had not received any previous chemotherapy were enrolled at 19 centres in France. Treatment consisted of 60 mg/m(2) intravenous doxorubicin followed by 1·1 mg/m(2) trabectedin in a 3 h intravenous infusion on day 1, both by the central venous route, and 6 mg subcutaneous pegfilgrastim on day 2, repeated every 3 weeks for up to six cycles. Surgery for residual disease was permitted. The primary endpoint was the proportion of patients achieving disease control, defined as complete or partial response or stable disease. Stratification was done by anatomical site and analyses were per protocol. This study is registered with ClinicalTrials.gov, number NCT02131480.
FINDINGS: Between July 28, 2010, and May 10, 2013, 109 patients were enrolled and treated, of whom 108 were assessable for response: 47 in the uterine leiomyosarcoma group and 61 in the soft-tissue leiomyosarcoma group. 32 (68%) patients in the uterine leiomyosarcoma group and 45 (74%) in the soft-tissue leiomyosarcoma group received all six cycles of treatment. Of 47 patients with uterine leiomyosarcoma, 28 (59·6%, 95% CI 44·3-73·6) achieved a partial response and 13 (27·7%, 15·6-42·6) stable disease; 41 (87·2%, 74·3-95·2) patients achieved disease control. Of 61 patients with soft-tissue leiomyosarcoma, two (3·3%, 95% CI 0·4-11·7) achieved a complete response, 22 (36·1%, 25·0-50·8) had a partial response, and 32 (52·5%, 40·8-67·3) had stable disease; 56 (91·8%, 81·9-97·3) of patients achieved disease control. The most common grade 3-4 treatment-associated adverse events were neutropenia (84 [78%] of 108 patients), increased alanine aminotransferase concentration (42 [39%]), thrombocytopenia (40 [37%]), anaemia (29 [27%]), febrile neutropenia (26 [24%]), and fatigue (21 [19%]).
INTERPRETATION: Despite expected but manageable toxic effects, these results support the activity of doxorubicin plus trabectedin as first-line treatment for uterine leiomyosarcoma and soft-tissue leiomyosarcoma. This combination should be developed further in a phase 3 trial against the present standard of care.
FUNDING: Pharmamar and Amgen.

Urakawa H, Tsukushi S, Kozawa E, et al.
Postoperative brain metastases in soft tissue sarcomas.
Clin Exp Metastasis. 2015; 32(4):345-51 [PubMed] Related Publications
Brain metastases (BMs) from soft tissue sarcoma (STS) are rare but lethal. We reviewed 187 consecutive patients with STS treated with definitive surgery in Nagoya University Hospital from 2004 to 2014. There were 10 patients with neurofibromatosis-1 (NF-1). We investigated estimated brain metastasis free survival (BMFS) after surgery and overall survival (OS) after BMs in STS. The factors that affected BMFS were also investigated. Eight of 187 patients (4.3%) developed BM with a median period of 18.2 (range 8.8-42.6) months after surgery. Seven of 8 BM patients had metastases at other sites. Estimated 5 year BMFS rate after surgery was 95.2%, and 3 month OS rate after BM was 25.0%. NF-1 (p<0.0001), histological subtype of MPNST (p=0.008), and primary tumor size≥5 cm (p=0.021) were significantly associated with increasing incidence of BM. In this study, postoperative BMs were common in patients with NF-1, MPNST, and large tumors. Considering the impact of NF-1 on BMFS, careful follow up for BM is necessary for NF-1 patients with metastases at other sites.

Zhu J, Gu J, Ma J, et al.
Histone deacetylase inhibitors repress chondrosarcoma cell proliferation.
J BUON. 2015 Jan-Feb; 20(1):269-74 [PubMed] Related Publications
PURPOSE: Due to the high resistance to conventional therapy, there is still no convincingly effective treatment for chondrosarcoma. As a promising new treatment strategy, histone deacetylase inhibitors (HDACIs) have been reported to induce cell arrest, apoptosis and differentiation in some kinds of malignancies, but how HDACi exert their effects on chondrosarcoma is not well understood yet.
METHODS: We investigated the effects of HDACIs trichostatin A (TSA) and sodium valproate (VPA) on chondrosarcoma cells in vitro and in vivo. The cell proliferation and cell cycle were examined in two chondrosarcoma cell lines, SW1353 and JJ012, by MTS and flow cytometry assays, respectively. The in vivo effects of HDACIs were investigated by assessing the chondrosarcoma growth in a mouse xenograft model.
RESULTS: Our results showed that TSA and VPA significantly repressed the proliferation of chondrosarcoma cells in a concentration-dependent manner. Flow cytometry indicated that TSA arrested the cell cycle in G2/M phase and VPA arrested the cell cycle in G1 phase. The tumor growth was markedly suppressed in mice treated with TSA and VPA.
CONCLUSIONS: HDACIs significantly repress the proliferation of chondrosarcoma cells in vitro and in vivo. Our findings imply that HDACIs may provide a novel therapeutic target for the treatment of chondrosarcoma.

Smith SM, Coleman J, Bridge JA, Iwenofu OH
Molecular diagnostics in soft tissue sarcomas and gastrointestinal stromal tumors.
J Surg Oncol. 2015; 111(5):520-31 [PubMed] Related Publications
Soft tissue sarcomas are rare malignant heterogenous tumors of mesenchymal origin with over fifty subtypes. The use of hematoxylin and eosin stained sections (and immunohistochemistry) in the morphologic assessment of these tumors has been the bane of clinical diagnosis until recently. The last decade has witnessed considerable progress in the understanding and application of molecular techniques in refining the current understanding of soft tissue sarcomas and gastrointestinal stromal tumors beyond the limits of traditional approaches. Indeed, the identification of reciprocal chromosomal translocations and fusion genes in some subsets of sarcomas with potential implications in the pathogenesis, diagnosis and treatment has been revolutionary. The era of molecular targeted therapy presents a platform that continues to drive biomarker discovery and personalized medicine in soft tissue sarcomas and gastrointestinal stromal tumors. In this review, we highlight how the different molecular techniques have enhanced the diagnosis of these tumors with prognostic and therapeutic implications.

Singh SS, Scott S, Bougie O, et al.
Technical update on tissue morcellation during gynaecologic surgery: its uses, complications, and risks of unsuspected malignancy.
J Obstet Gynaecol Can. 2015; 37(1):68-81 [PubMed] Related Publications
OBJECTIVE: To review the use of tissue morcellation in minimally invasive gynaecological surgery.
OUTCOMES: Morcellation may be used in gynaecological surgery to allow removal of large uterine specimens, providing women with a minimally invasive surgical option. Adverse oncologic outcomes of tissue morcellation should be mitigated through improved patient selection, preoperative investigations, and novel techniques that minimize tissue dispersion.
EVIDENCE: Published literature was retrieved through searches of PubMed and Medline in the spring of 2014 using appropriate controlled vocabulary (leiomyomsarcoma, uterine neoplasm, uterine myomectomy, hysterectomy) and key words (leiomyoma, endometrial cancer, uterine sarcoma, leiomyosarcoma, morcellation, and MRI). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date limits but results were limited to English or French language materials. Searches were updated on a regular basis and incorporated in the guideline to August 2014. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.
VALUES: The quality of evidence in this document was rated using the criteria described in the report of the Canadian Task Force on Preventive Health Care. (Table 1) BENEFITS, HARMS, AND COSTS: Gynaecologists may offer women minimally invasive surgery and this may involve tissue morcellation and the use of a power morcellator for specimen retrieval. Women should be counselled that in the case of unexpected uterine sarcoma or endometrial cancer, the use of a morcellator is associated with increased risk of tumour dissemination. Appropriate training and safe practices should be in place before offering tissue morcellation. SUMMARY STATEMENTS: 1. Uterine sarcomas may be difficult to diagnose preoperatively. The risk of an unexpected uterine sarcoma following surgery for presumed benign uterine leiomyoma is approximately 1 in 350, and the rate of leiomyosarcoma is 1 in 500. (II-2) This risk increases with age. (II-2) 2. An unexpected uterine sarcoma treated by primary surgery involving tumour disruption, including morcellation of the tumour, has the potential for intra-abdominal tumour-spread and a worse prognosis. (II-2) 3. Uterus-sparing surgery remains a safe option for patients with symptomatic leiomyomas who desire future fertility. (II-1) RECOMMENDATIONS: 1. Techniques for morcellation of a uterine specimen vary, and physicians should consider employing techniques that minimize specimen disruption and intra-abdominal spread. (III-C) 2. Each patient presenting with uterine leiomyoma should be assessed for the possible presence of malignancy, based on her risk factors and preoperative imaging, although the value of these is limited. (III-C) 3. Preoperative endometrial biopsy and cervical assessment to avoid morcellation of potentially detectable malignant and premalignant conditions is recommended. (II-2A) 4. Hereditary cancer syndromes that increase the risk of uterine malignancy should be considered a contraindication to uncontained uterine morcellation. (III-C) 5. Uterine morcellation is contraindicated in women with established or suspected cancer. (II-2A) If there is a high index of suspicion of a uterine sarcoma prior to surgery, patients should be advised to proceed with a total abdominal hysterectomy, bilateral salpingectomy, and possible oophorectomy. (II-2C) A gynaecologic oncology consultation should be obtained. 6. Tissue morcellation techniques require appropriate training and experience. Safe practice initiatives surrounding morcellation technique and the use of equipment should be implemented at the local level. (II-3B) 7. Morcellation is an acceptable option for retrieval of benign uterine specimens and may facilitate a minimally invasive surgical approach, which is associated with decreased perioperative risks. Each patient should be counselled about the possible risks associated with the use of morcellation, including the risks associated with underlying malignancy. (III-C).

Gaspard D, Raja H, Arya R, et al.
A case report on the diagnosis of a rare pleural tumor with endobronchial ultrasound: breaking new boundaries.
Medicine (Baltimore). 2015; 94(10):e561 [PubMed] Related Publications
Convex endobronchial ultrasound (C-EBUS)-guided transbronchial needle aspiration (TBNA) is an effective tool for the diagnosis of hilar, mediastinal, and central parenchymal lung lesions. However, it has a limited utility for pleural-based masses. We report a unique case of a pleural synovial sarcoma recurrence that was diagnosed by C-EBUS. The patient had a history of inguinal synovial sarcoma. He presented with cough and chest pain. Imaging of chest revealed large right pleural mass. Bronchoscopy with EBUS-TBNA diagnosed pleural recurrence of synovial sarcoma. He underwent radical resection and pathological examination confirmed the diagnosis of pleural synovial sarcoma. He experienced complete recovery and resolution of symptoms. Synovial sarcoma should be included in the differential diagnosis of pleural masses. Convex EBUS-guided biopsies can provide adequate diagnosis of large pleural tumors adjacent to the central airways without need for more invasive diagnostic procedures.

Lightner AL, Shurell E, Dawson N, et al.
A single-center experience and review of the literature: 64 cases of phyllodes tumors to better understand risk factors and disease management.
Am Surg. 2015; 81(3):309-15 [PubMed] Related Publications
Phyllodes tumors of the breast are rare fibroepithelial tumors that are characterized as benign, borderline, or malignant based on cellular characteristics such as stromal overgrowth and number of mitoses. Currently, there is a lack of consensus on risk factors and management of patients with phyllodes tumors, which has led to variation in treatment patterns as well as patient outcomes across many institutions. This study seeks to understand the clinicopathologic features, risk factors for local and metastatic recurrence, and clinical outcomes of patients with phyllodes tumors to better define optimal treatment patterns.

Liu X, Ogasawara S, Kaneko MK, et al.
A novel monoclonal antibody SMab-2 recognizes endogenous IDH2-R172S of chondrosarcoma.
Biochem Biophys Res Commun. 2015; 459(4):636-42 [PubMed] Related Publications
Isocitrate dehydrogenase 2 (IDH2) mutations have been reported in gliomas, osteosarcomas, cartilaginous tumors, giant cell tumors of bone, and acute myeloid leukemias. Although IDH2 catalyzes the oxidative carboxylation of isocitrate to α-ketoglutarate (α-KG) in mitochondria, mutated IDH2 proteins possess the ability to change α-KG into the oncometabolite R(-)-2-hydroxyglutarate (2-HG). To date, several monoclonal antibodies (mAbs) specific for IDH2 mutations have been established, such as KMab-1 against IDH2-R172K, MMab-1 against IDH2-R172M, and WMab-1 against IDH2-R172W. Although a multi-specific mAb MsMab-1 reacted with IDH2-R172G and IDH2-R172S, a mono-specific mAb against IDH2-R172S has not been established. In this study, we established a novel mAb SMab-2, which recognizes IDH2-R172S but not with wild type IDH2 in ELISA. Although SMab-2 reacted with both IDH1-R132S and IDH2-R172S expressed in Escherichia coli, it reacted with only IDH2-R172S expressed in U-2 OS osteosarcoma cells. Furthermore, SMab-2 recognized endogenous IDH2-R172S protein expressed in SW1353 chondrosarcoma cells in Western blot and immunocytochemical analyses. SMab-2 is expected to be useful for diagnosis of IDH2-R172S-bearing tumors.

Rauh-Hain JA, Buskwofie A, Clemmer J, et al.
Racial disparities in treatment of high-grade endometrial cancer in the Medicare population.
Obstet Gynecol. 2015; 125(4):843-51 [PubMed] Related Publications
OBJECTIVE: To examine the patterns of care and survival for African American and white women with high-grade endometrial cancer.
METHODS: The linked Surveillance, Epidemiology, and End Results and Medicare databases were queried to identify patients diagnosed with grade 3 endometrioid endometrial adenocarcinoma, uterine carcinosarcoma, uterine clear cell carcinoma, and uterine serous carcinoma between 1992 and 2009. The effect of treatment modality on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model.
RESULTS: A total of 9,042 patients met study eligibility criteria. African Americans had definitive surgery (76.8% compared with 88.7%; P<.001) less frequently. There was no difference in the rate of adjuvant treatment between the groups. In the crude models for both all-cause mortality and cancer-specific mortality, African American women had an increased overall and disease-specific hazard of death compared with white women. The overall hazard ratio for African American women was 1.6 (95% confidence interval [CI] 1.5-1.7), and the disease-specific hazard ratio was 1.5 (95% CI 1.3-1.6). Over the entire study period, after adjusting for stage, age, period of diagnosis, registry region, urban compared with rural setting, marital status, treatment, surgery, socioeconomic status, and comorbidities, there was no association between race and lower disease-specific survival (hazard ratio 1.1, 95% CI 1-1.2; P=.06).
CONCLUSION: African American women had lower cancer-specific and all-cause survival compared with white women. Controlling for treatment, sociodemographics, comorbidities, and histopathologic variables eliminated the difference between African American and white women in the disease-specific analysis.

Nakano K, Motoi N, Takahashi S
The CYVADIC regimen as a combination chemotherapy treatment option for advanced soft tissue sarcomas originating from the non-extremities.
Intern Med. 2015; 54(2):187-93 [PubMed] Related Publications
OBJECTIVE: Soft tissue sarcoma (STS) originating from the non-extremities has a poor prognosis and risk for visceral crisis; therefore, combination chemotherapy with a high response rate is desired.
METHODS: We retrospectively reviewed the cases of 30 patients with advanced STS that originated from the non-extremities who were treated between October 2005 and February 2012 at our institute with the CYVADIC chemotherapy regimen, which consists of cyclophosphamide, vincristine, doxorubicin, and dacarbazine. The patients' objective responses, progression-free survival (PFS), and overall survival (OS) were evaluated, and a statistical analysis was conducted to identify the predictive factors related to response and survival.
RESULTS: The median follow-up time was 16.5 months. The response rate was 33%, the median PFS was 7.4 months, and the 1-year OS was 81% (the OS did not reach the median). The median number of treatment cycles was six. Eleven patients failed to complete 6 cycles due to disease progression. The number of involved organs (>3) was a significant predictive factor of early refractoriness by the logistic regression analysis. Thirteen patients had an objective response or PFS longer than 1 year, and an alkaline phosphatase (ALP) level within the normal limits were the significant predictive factors of a good response.
CONCLUSION: The patients' responses to the CYVADIC therapy for advanced STS originating from the non-extremities were moderate; therefore, CYVADIC therapy may be a treatment option of choice as combination chemotherapy for such patients. We propose that the number of involved organs and ALP concentration may be useful measures to predict the response to the CYVADIC therapy.

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