Treatment Of Liposarcoma Research Articles

Lipomatous tumours of the head and neck: a spectrum of biological behaviour.

Lipomatous tumours are rare in the head and neck region. Their biological behaviour varies greatly, from absolutely benign to histologically benign but locally infiltrative and, finally, invasive with metastatic potential. Each lipomatous tumour has to be treated accordingly. It is of paramount importance before eventual surgery is planned to perform adequate imaging, diagnostic biopsy and careful assessment. Only in small (<5 cm), superficial soft tissue tumours or when magnetic resonance imaging has demonstrated specific features of lipoma, may diagnostic biopsy be omitted. In these cases, expectant management or simple excision is appropriate. Adequate preoperative diagnosis is important to assure adequate tumour control as well as optimal functional and cosmetic outcome. The major problem in the treatment of lipomatous tumours of the head and neck region is the presence of nearby delicate structures. Especially, wide surgical excision of liposarcomas may be hindered by anatomic constraints and may result in impaired functional and cosmetic outcome. Neoadjuvant radiotherapy and specific systemic chemotherapy may be helpful in the treatment of liposarcoma, especially when unresectable or when primary surgery is expected to result in poor oncological, functional or cosmetic outcome. Greater emphasis placed on the underlying biology of individual sarcoma subtypes, development and evaluation of novel therapies and greater specificity in the selection of chemotherapy agents based on activity in individual histological subtypes are expected to lead to improved efficacy of systemic treatment.

Synergistic Effects of Targeted PI3K Signaling Inhibition and Chemotherapy in Liposarcoma

While liposarcoma is the second most common soft tissue malignant tumor, the molecular pathogenesis in this malignancy is poorly understood. Our goal was therefore to expand the understanding of molecular mechanisms that drive liposarcoma and identify therapeutically-susceptible genetic alterations. We studied a cohort of high-grade liposarcomas and benign lipomas across multiple disease sites, as well as two liposarcoma cell lines, using multiplexed mutational analysis. Nucleic acids extracted from diagnostic patient tissue were simultaneously interrogated for 150 common mutations across 15 essential cancer genes using a clinically-validated platform for cancer genotyping. Western blot analysis was implemented to detect activation of downstream pathways. Liposarcoma cell lines were used to determine the effects of PI3K targeted drug treatment with or without chemotherapy. We identified mutations in the PIK3CA gene in 4 of 18 human liposarcoma patients (22%). No PIK3CA mutations were identified in benign lipomas. Western blot analysis confirmed downstream activation of AKT in both PIK3CA mutant and non-mutant liposarcoma samples. PI-103, a dual PI3K/mTOR inhibitor, effectively inhibited the activation of the PI3K/AKT in liposarcoma cell lines and induced apoptosis. Importantly, combination with PI-103 treatment strongly synergized the growth-inhibitory effects of the chemotherapy drugs doxorubicin and cisplatin in liposarcoma cells. Taken together, these findings suggest that activation of the PI3K/AKT pathway is an important cancer mechanism in liposarcoma. Targeting the PI3K/AKT/pathway with small molecule inhibitors in combination with chemotherapy could be exploited as a novel strategy in the treatment of liposarcoma.

Trabectedin: Safety and Efficacy in the Treatment of Advanced Sarcoma

Soft tissue sarcomas (STS) are a rare group of malignancies with multiple different subtypes. Close to half of intermediate or high grade STS develop metastatic disease. Treatment of recurrent/metastatic sarcomas is quite challenging with only a few drugs showing measurable benefits. Trabectedin (ecteinascidin 743, ET-743, Yondelis) is a newly developed alkylating agent that has shown significant broad spectrum potential as a single agent second line drug alone or in combination particularly in the treatment of liposarcomas and leiomyosarcomas. Clinical benefit rates seem to favor its use especially in pretreated patients with recurrent/metastatic disease. The drug is well tolerated in general but hepatotoxicity and hematologic side effects are common. Approved in Europe, the currently ongoing Phase III trials along with the already existing clinical evidence may provide enough data for the Food and Drug Administration for an approval in the US.

New frontiers in the treatment of liposarcoma, a therapeutically resistant malignant cohort

The adipogenic origin-derived liposarcoma (LPS) family is the most common soft tissue sarcoma histological subtype. This group is composed of three categories as per the 2002 WHO guidelines: (1) well-differentiated and dedifferentiated liposarcoma (WDLPS/DDLPS); (2) myxoid and round cell liposarcoma (MLS and RCL); and (3) pleomorphic liposarcoma (PLS). While clustered together, these histological subtypes are widely diverse in their clinical, pathological, and molecular characteristics. In general, surgery still remains the mainstay of LPS therapy and the only approach offering the potential of cure. Effective therapeutic strategies for locally advanced and metastatic disease are currently lacking and are crucially needed. With the current gradually increasing knowledge of LPS genetic- and epigenetic-associated deregulations, the ultimate goal is to develop drugs that can specifically eliminate LPS cells while sparing normal tissues. This tumor-tailored target-orientated approach will hopefully result in a significant improvement in the outcome of patients suffering from these poor prognosis malignancies.

Giant neck liposarcoma with pathological clavicular fracture

Liposarcomas generally originate in the extremities or retroperitoneum, they are very unusual in the head and neck region, and extremely rare in the thorax. The mainstay of treatment for liposarcomas is surgical excision. We report a very unusual case, not reported before to our knowledge, of a well-differentiated liposarcoma arising from the supraclavicular fossa that produces a pathological clavicular fracture. The patient underwent complete resection of the lesion, without damage of the cervical nerves. Eight months after the surgery the patient is free of recurrence. We demonstrate that giant liposarcomas can be resected completely without morbidity.

Heterogeneous in vitro effects of doxorubicin on gene expression in primary human liposarcoma cultures

BackgroundDoxorubicin is considered one of the most potent established chemotherapeutics in the treatment of liposarcoma; however, the response rates usually below 30%, are still disappointing. This study was performed to identify gene expression changes in liposarcoma after doxorubicin treatment.MethodsCells of 19 primary human liposarcoma were harvested intraoperatively and brought into cell culture. Cells were incubated with doxorubicin for 24 h, RNA was isolated and differential gene expression was analysed by the microarray technique.ResultsA variety of genes involved in apoptosis were up and down regulated in different samples revealing a heterogeneous expression pattern of the 19 primary tumor cell cultures in response to doxorubicin treatment. However, more than 50% of the samples showed up-regulation of pro-apoptotic genes such as TRAIL Receptor2, CDKN1A, GADD45A, FAS, CD40, PAWR, NFKBIA, IER3, PSEN1, RIPK2, and CD44. The anti-apoptotic genes TNFAIP3, PEA15, Bcl2A1, NGFB, and BIRC3 were also up-regulated. The pro-apoptotic CD14, TIA1, and ITGB2 were down-regulated in more than 50% of the tumor cultures after treatment with doxorubicin, as was the antiapoptotic YWHAH.ConclusionDespite a correlation of the number of differentially regulated genes to the tumor grading and to a lesser extent histological subtype, the expression patterns varied strongly; however, especially among high grade tumors the responses of selected apoptosis genes were similar. The predescribed low clinical response rates of low grade liposarcoma to doxorubicin correspond to our results with only little changes on gene expression level and also divergent findings concerning the up- and down-regulation of single genes in the different sarcoma samples.

Liposarcoma treatment: Role of radiotherapy and chemotherapy

10578 Background: The best adjuvant treatment for soft tissue sarcomas is still unclear. Soft tissue sarcomas is an eterogenous group of several different hystotypes. The aim of this retrospective study is to evaluate prognostic factors and treatments. Methods: All liposarcoma cases evaluated in our Pathology from Jan 1985 to December 2005 were reviewed: 299 cases of liposarcoma were found of these only 155 were treated at Rizzoli since their first diagnosis. Metastatic since diagnosis and pediatric cases were excluded. Of these 155 pts only 122 had localized liposarcoma of soft tissue and adequate informations and follow up. Results: Male were 71 and female 51, Median age 47 (15–85). Histology was as follows: mixoid 62, round cell 33, pleomorphic 27. Grading according to FNCCL was G1=18, G2=51, G3=53. Median tumor volume was 183 cm3 (8–3,800), mean 401. Surgical margins were adequate in 84 patients (66.4%) unadequate in 34 (27.9%), 4 missing. Treatment received were: 18 no treatment besides surgery, pres...

側頭部脂肪肉腫治療後の著しいはん痕性開口障害に対し筋突起切除術を施行した１例

We report a case of severe trismus due to cicatrical changes in the left temporal region after treatment for liposarcoma. A 51-year-old woman was referred to our hospital because of severe trismus. Mouth opening range was only 8 mm.Computed tomography and magnetic resonance imaging showed no findings of temporomandibular ankylosis. Decreased signal intensity around the left coronoid process was seen on magnetic resonance images. A diagnosis of severe trismus due to cicatrical changes around the left coronoid process was strongly suggested, and coronoidectomy was performed. At operation, the mouth could be opened up to 45mm. A mouth opening range of 40mm has been maintained by the mouth opening training after operation.

CHILDHOOD LIPOSARCOMA: A Single-Institutional Twenty-Year Experience

A retrospective observational study was performed on a series of 12 consecutive pediatric patients treated over a 20-year period at the Istituto Nazionale Tumori, Milano. Conservative surgery was the treatment of choice in all patients; radical excision was obtained at diagnosis in 9 cases and after primary chemotherapy in 1 case. Five patients were subjected to surgery alone, and one to postoperative radiotherapy. After a median follow-up of 11 years (range 1-20), all the patients were alive without evidence of disease, 11 in first complete remisson, and 1 after local relapse. In agreement with other reports, the authors underline the unquestionable pivotal role of radical surgery in the treatment of liposarcoma. The high proportion of resectable tumors accounts for the excellent survival of the patients in this study. The role of both adjuvant chemotherapy and radiotherapy is uncertain and awaits multicentric cooperative prospective studies.

Radiotherapy in the treatment of liposarcoma

Radiotherapy in the treatment of liposarcoma