Adult Soft Tissue Sarcomas Research Articles

Mediastinal Myxoid Liposarcoma with Intrapericardial Involvement and Large Pericardial Effusion

Liposarcoma is the name given to a group of soft tissue sarcomas (STSs) with adipocytic differentiation. As a group, liposarcomas are the second most common STSs in adults. In 1951 Kozonis et al published that in the English language only four cases of liposarcomas originating in the mediastinum had been described. Primary mediastinal liposarcoma is an uncommon neoplasm of intrathoracic origin. We present the case of a 47-year-old woman diagnosed with a large mediastinal mass with intrapericardial invasion and massive pericardial effusion; biopsies showed a mediastinal liposarcoma.

Neoadjuvant Chemotherapy and Radiation Therapy for Soft Tissue Sarcoma in Adults: A Single-Institution Retrospective Review

Neoadjuvant Chemotherapy and Radiation Therapy for Soft Tissue Sarcoma in Adults: A Single-Institution Retrospective Review

The Effect of Margin Status and Radiation Therapy on Survival in Adult Retroperitoneal Soft Tissue Sarcomas

The Effect of Margin Status and Radiation Therapy on Survival in Adult Retroperitoneal Soft Tissue Sarcomas

Cyclophosphamide versus ifosfamide for paediatric and young adult bone and soft tissue sarcoma patients.

Alkylating agents, such as cyclophosphamide and ifosfamide, play a major role in the improved survival of children and young adults with bone and soft tissue sarcoma. However, there is still controversy as to their comparative anti-tumour efficacy and possible adverse effects. This is the second update of the first systematic review evaluating the state of evidence on the effectiveness of cyclophosphamide as compared to ifosfamide for paediatric and young adult patients with sarcoma. The primary obective was to compare the effectiveness, that is response rate, event-free survival and overall survival, of cyclophosphamide with that of ifosfamide for paediatric and young adult patients with sarcoma. Secondary objectives were to determine effects of these agents on toxicities (including late effects) and quality of life. We searched CENTRAL (The Cochrane Library 2015, issue 2), MEDLINE/PubMed (from 1966 to March 2015) and EMBASE/Ovid (from 1980 to March 2015) with prespecified terms. In addition, we searched reference lists of relevant articles, conference proceedings and ongoing trial databases (www.controlled-trials.com; searched June 2015). Randomised controlled trials (RCTs) or controlled clinical trials (CCTs) comparing cyclophosphamide and ifosfamide for the treatment of different types of sarcoma in paediatric and young adult patients (aged less than 30 years at diagnosis). Chemotherapy other than either cyclophosphamide or ifosfamide should have been the same in both treatment groups. Two authors independently performed the study selection. No studies meeting the inclusion criteria of the review were identified. No RCTs or CCTs comparing the effectiveness of cyclophosphamide and ifosfamide in the treatment of bone and soft tissue sarcoma in children and young adults were identified. Therefore no definitive conclusions can be made about the effects of cyclophosphamide and ifosfamide in these patients. Based on the currently available evidence, we are not able to give recommendations for clinical practice. More high-quality research is needed.

Head and neck soft-tissue sarcoma in adults

Adult soft-tissue sarcoma is rare but aggressive, with incidence around 5 per 100,000 per year. Head and neck locations are infrequent. Genetic disease and irradiation are risk factors. The diagnosis needs to be known in order to avoid treatment delay. There are about 50 histologic subtypes, with different patterns and prognoses. Pathologic review and the development of molecular techniques are therefore essential. Prognosis in adult head and neck soft-tissue sarcoma (HNSTS) is poor: 5-year overall survival, about 60%. Recurrence is most often local. Prognostic factors are: tumor size and local extension, histologic grade and margin status. There are few targeted management guidelines. Surgical resection with negative margins is the primary treatment. Postoperative radiation therapy can improve prognosis. The role of chemotherapy is not well established. HNSTS should be treated in a reference center, with multidisciplinary staff following national network guidelines. Several factors are still unknown. The purpose of this article is to summarize the state of knowledge in adult HNSTS.

3433 Peripheral neuropathy caused by vincristine-containing chemotherapy for adult soft tissue sarcoma: A comparison between young and older adults

3433 Peripheral neuropathy caused by vincristine-containing chemotherapy for adult soft tissue sarcoma: A comparison between young and older adults

3444 Low dose oral cyclophosphamide (LDOC) with prednisolone in the treatment of advanced adult soft tissue sarcoma (STS)

3444 Low dose oral cyclophosphamide (LDOC) with prednisolone in the treatment of advanced adult soft tissue sarcoma (STS)

Hsp90 inhibition by AUY922 as an effective treatment strategy against myxoid liposarcoma

Liposarcoma is one of the most common soft tissue sarcomas in adults. Recognized histological subtypes include well differentiated/dedifferentiated liposarcoma (WD/DDLS), myxoid liposarcoma (MLS) and pleomorphic liposarcoma. Currently, there are no proper subtype-specific treatments due to the genetic, histological and clinical heterogeneity of the liposarcoma subentities. In the past decade, the rising understanding of the various genetic and molecular aberrations in liposarcoma led to the development of novel alternative therapeutic strategies. One such therapy is the inhibition of the heat shock protein 90 (Hsp90) which is overexpressed in liposarcomas. In this study, we dissect the functional role of a novel potent Hsp90 inhibitor NVP-AUY922 (AUY922) in different cell lines of myxoid (MLS402, MLS1765) and undifferentiated (SW872) liposarcomas. We show that compared with 17-AAG treatment, lower concentrations of AUY922 achieve markedly cytotoxic effects on tumor cell viability. Combination treatment of AUY922 (20 nM) with Doxorubicin (300 nM) yielded a further reduction in cell viability in comparison to Doxorubicin alone. In vivo, we document an inhibition of tumor growth after AUY922 treatment. Further analyses revealed that Hsp90-inhibition induces apoptotic cell death and cell cycle arrest. In addition, we report striking perturbations of subtype-specific pattern in Raf/MEK/ERK and PI3K signaling after AUY922 application. In conclusion, our results provide evidence that Hsp90-inhibition by AUY922 may be a promising alternative therapeutic strategy for myxoid liposarcoma patients.

Survival post relapse of soft tissue limb sarcomas: A 10-year retrospective review.

e21522 Background: Adult limb soft tissue sarcomas (STS’s) are rare, solid tumours accounting for less than 1% of all cancers. Such cases are best managed at institutions which provide expert multi...

FGFR2 is overexpressed in myxoid liposarcoma and inhibition of FGFR signaling impairs tumor growth in vitro.

Myxoid liposarcomas account for more than one third of liposarcomas and about 10% of all adult soft tissue sarcomas. The tumors are characterized by specific chromosomal translocations leading to the chimeric oncogenes FUS-DDIT3 or EWS1R-DDIT3. The encoded fusion proteins act as aberrant transcription factors. Therefore, we implemented comparative expression analyses using whole-genome microarrays in tumor and fat tissue samples. We aimed at identifying differentially expressed genes which may serve as diagnostic or prognostic biomarkers or as therapeutic targets. Microarray analyses revealed overexpression of FGFR2 and other members of the FGF/FGFR family. Overexpression of FGFR2 was validated by qPCR, immunohistochemistry and western blot analysis in primary tumor samples. Treatment of the myxoid liposarcoma cell lines MLS 402 and MLS 1765 with the FGFR inhibitors PD173074, TKI258 (dovitinib) and BGJ398 as well as specific siRNAs reduced cell proliferation, induced apoptosis and delayed cell migration. Combination of FGFR inhibitors with trabectedin further increased the effect. Our study demonstrates overexpression of FGFR2 and a functional role of FGFR signaling in myxoid liposarcoma. As FGFR inhibition showed effects on proliferation and cell migration and induced apoptosis in vitro, our data indicate the potential use of FGFR inhibitors as a targeted therapy for these tumors.

Extraskeletal osteosarcoma of the hand: the role of marginal excision and adjuvant radiation therapy.

Extraskeletal osteosarcoma of the hand is rare, and its optimal modality of local control is not currently known. A literature search was performed to identify studies that describe the treatment and outcomes of extraskeletal osteosarcoma. A second literature search was performed to identify studies that describe the treatment and outcomes of extraskeletal osteosarcoma of the hand specifically. The role of adjuvant radiation for extraskeletal osteosarcoma is not well defined. All cases in the literature describing treatment of extraskeletal osteosarcoma of the hand utilized amputation, and none of the patients described received radiation therapy. However, there are multiple reports showing excellent local control, minimal toxicity, and superior functional outcome with limb conservation and radiation rather than amputation of the hand in pediatric and adult soft tissue sarcoma. For extraskeletal osteosarcoma of the hand, we recommend a treatment approach with the goal of preservation of form and function using limb-sparing surgery and planned postoperative radiation.

Management of extremity malignant fibrous histiocytoma: A 10-year experience

Summary Background Malignant fibrous histiocytoma (MFH) is a common soft-tissue sarcoma in adults, which commonly affects the extremities, trunk, head, and neck. Of these regions, the extremities are more often affected. However, only a few studies have specifically investigated the clinical behavior and prognosis of this malignancy, especially in East Asian populations. Aims and objectives We collected data on MFH cases for a period of 10 years and present our experience here in treating patients with extremity MFH. Materials and methods This study was a retrospective analysis of patients with extremity MFH treated in the Department of Plastic Surgery at National Cheng Kung University Hospital between January 2004 and December 2013. Data on patient profiles, surgical resection, radiotherapy, and chemotherapy were all reviewed. The patients were followed up regarding their local recurrences and survivals. Results Thirteen patients (6 men and 7 women) were enrolled in this study. The mean age of the patients was 57.9 years (range, 33–82 years). The sizes of the clinical tumors ranged from 1.7 to 15 cm in a maximal linear dimension (mean, 7.3 cm), and 76.9% of the tumors developed in the lower extremities. The average follow-up time was 63.5 months. One patient received limb amputation, and 12 patients were treated with limb salvage including marginal or wide excisions. Adjuvant radiotherapy was performed in 10 patients whose tumor sizes exceeded 5 cm or who exhibited inadequate excision or recurrence. Chemotherapy was performed in six patients who exhibited a distant metastasis or vessel invasion. The local and distant recurrence rates were 53.8% and 30.8%, respectively. A total of 42.9% of patients with local recurrence developed distant metastases. The surgical margin was the only significant factor of local disease control, and distant metastasis was the only factor relevant to the overall survival (OS). Conclusion An adequate resection margin during treatment for the primary MFH tumor achieves optimal results for local disease control. It influences the OS rate, because local-recurrence-related distant metastasis is significantly associated with high mortality.

Primary pulmonary malignant fibrous histiocytoma.

Malignant fibrous histiocytoma (MFH) is one of the most common adult soft tissue sarcomas. MFH is very aggressive and is most often found in the extremities and the retroperitoneum, but it can manifest at other sites. Though the lungs are the most common sites of metastasis, they rarely present there as a primary tumor. Our report describes a rare case of a primary MFH tumor in the lung. Careful diagnostic procedure should be followed to ensure the tumor does not have extrapulmonary origins. Though MFH is highly invasive and deadly, surgical excision of the tumor has been shown to be successful.

Paratesticular rhabdomyosarcoma of a young adult.

Sarcomas represent large and diverse group of malignant tumours, originating from mesenchymal cells. Nearly 15% of all childhood tumours and about 1% of all tumours in adults are sarcomas [1]. The incidence of adult soft tissue sarcomas in Europe is 5/100,000 [2]. Rhabdomyosarcoma accounts for 4.6% of all soft tissue sarcomas and it is the most common paediatric sarcoma, while it is extremely rare in adults [3].

Comparison of Response Evaluation Criteria in Solid Tumours and Choi criteria for response evaluation in patients with advanced soft tissue sarcoma treated with trabectedin: A retrospective analysis

BackgroundTo assess the additional value of density measurement using contrast-enhancement sequences (Choi assessment) in a real-life cohort of adult soft tissue sarcoma patients treated with trabectedin. MethodsEligibility criteria included adults (age ⩾18) treated between 01/2007 and 12/2011, with at least two trabectedin cycles after failure or intolerance to doxorubicin/ifosfamide. Baseline and first computed tomography (CT)-scans were centrally reviewed by an experienced radiologist. ResultsThe retrospective cohort consists of 134 (73 female) patients treated with trabectedin 1.5mg/m2 given as a 24-h infusion every 3weeks. Patients received a median of five trabectedin cycles (range: 2–33) and the main cause of discontinuation was progressive disease (PD) (n=105, 78.4%). Response Evaluation Criteria in Solid Tumours (RECIST) assessment was feasible in 128 (95.5%) patients, with Choi assessment performed in 92 (68.7%) patients, generally due to inadequate sequences or exclusive lung metastases. Concordance between both methods was fair (Kappa=0.290). We identified five patients with false PD (i.e. PD according to RECIST but stable disease/partial response as per Choi). Univariate analysis did not identify any predictive factors for false PD. Median overall survival (OS) of patients with PD as per RECIST but stable disease/partial response (SD/PR) according to Choi was better than for patients with PD according to both RECIST and Choi (14months versus 8months; p=0.052). ConclusionsChoi assessment may identify patients with false PD who achieved improved efficacy outcomes, suggesting that trabectedin may delay tumour progression even in the case of non-dimensional response. Dual size and tumour density assessment may be more suitable to evaluate responses to trabectedin in sarcoma patients as well as to improve the decision-making strategies for the continuation of trabectedin therapy.

Primary epidural liposarcoma of the cervical spine: Technical case report and review of the literature

Abstract Liposarcoma is the most common soft tissue sarcoma in adults. These tumors have a high incidence of osseous metastases, with a propensity to the spine; however, primary spinal involvement is very rare. A 56-year-old female patient presented with a 4 month history of cervical pain, including radiation to both upper limbs, without radicular distribution. Magnetic resonance imaging (MRI) showed an epidural lesion with gadolinium enhancement and bilateral extension into the intervertebral neural foramina (C5–C7), with spreading on the right side of the tumor into paravertebral tissue. The histopathological diagnosis was myxoid liposarcoma. To our knowledge it is the first case of primary myxoid liposarcoma of the cervical spine in the literature. Although rare, our case demonstrates that liposarcoma should be considered in the differential diagnosis of cervical tumors.

Abstract 5196: Different miRNAs expression in leiomyosarcoma and undifferentiated pleomorphic sarcoma

Abstract Rare and highly aggressive adult soft tissue sarcomas, leiomyosarcoma (LMS) and undifferentiated pleomorphic sarcoma (UPS), contain complex genomics characterized by a multitude of rearrangements, amplifications and deletions. Since differential diagnosis between the two sarcoma histotypes continues to remain a challenge, we attempted to identify a specific signature useful for improving the differential diagnosis, and we performed miRNA profiling on series of LMS and UPS samples stored at Rizzoli biobank. First, we investigated the different miRNA expression profile in 20 primary sarcoma samples, 10 high-grade LMS and 10 UPS, MFH-like, using miRNA array technique. The top 5 differentially expressed (p<0.01) miRNAs (miR-199b-5p, miR-320a, miR-199a-3p, miR-126, miR-22) were validated by RT-PCR on a series of further 27 UPS and 21 LMS. Confirming our microarray data, an higher expression of miR-199-5p and a lower expression of miR-320a was seen in UPS when compared to LMS. To evaluate the potential role of the above selected miRNAs, the gene targets recognized by three different target prediction databases (miRBase, TargetScan , miRanda) were combined with a list of LMS- and UPS-associated genes reported in literature. From an integrated analysis, IMP3, ROR2, MDM2, CDK4, and UPA genes were identified. By immunohistochemistry analysis, most of them showed strong protein expression in LMS group. Our data suggest a potential role of miR-320a and miR-199-5p in LMS and UPS development and expand our knowledge about these complex sarcoma histotypes. Association analysis between expression and chromosomal locations of miRNAs are ongoing to identify chromosomal regions involved in these tumors. Citation Format: Laura Pazzaglia, Mohamed Guled, Ioana Borze, Maria Serena Benassi, Piero Picci, Sakari Knuutila. Different miRNAs expression in leiomyosarcoma and undifferentiated pleomorphic sarcoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5196. doi:10.1158/1538-7445.AM2014-5196

Adult sinonasal soft tissue sarcoma: analysis of 48 cases from the French Sarcoma Group database.

The aim of this study was to determine the frequency of primary sinonasal adult sarcoma, identify histological subtypes, and analyze prognostic factors. Retrospective review. Forty-eight adult sinonasal sarcomas included in the French Sarcoma Group database (Conticabase) were reviewed. The most frequent tumor types were alveolar rhabdomyosarcoma (33.3%), embryonal rhabdomyosarcoma (14,6%), unclassified sarcoma (14.6%), and leiomyosarcoma (12.5%). All round cell tumors were rhabdomyosarcomas. The 5-year overall survival (OS), metastasis-free survival (MFS), and local recurrence-free survival (LRFS) rates were 62.3%, 73%, and 88.8%, respectively. Histotype was a prognostic factor for OS, MFS, and LRFS, with the worst prognosis associated with rhabdomyosarcomas, regardless of the subtype. The tumor grade influenced the OS and MFS. Surgery was a predictive factor for a complete response. These results suggest that sinonasal tract should be considered as an unfavorable site for rhabdomyosarcoma. Moreover, surgery should always be considered in treatment.

Liposarcoma in the axilla developed from a longstanding lipoma.

Liposarcoma in the axilla developed from a longstanding lipoma.

English

Liposarcoma is the most common soft tissue sarcoma in adults, which usually involves lower extremities, trunk, retroperitoneum, or abdominal cavity. Till date, only a few cases of enormously huge liposarcoma have been reported. We report a case of huge mass of size 60 × 45 × 35 cm in scapular region in a middle aged person; which developed from a preexisting lipoma and was gradually increased in size as sub-mucosal non-ulcerated mass and which ultimately become ulcerated and infected with gas forming organisms. This tumor was successfully resected in toto under general anesthesia and after follow up to two years no recurrence was reported.