0000000000131853
AUTHOR
Marianna Silletta
BMI as a risk factor for toxicities in patients with advanced soft tissue sarcoma treated with trabectedin.
e22517 Background: Since the first steps of its clinical development, trabectedin was noticed to be extremely active against myxoid liposarcoma (MLS), whose pathogenesis seems to be associated to the presence of the t(12;16)(q13;p11) translocation, resulting in the expression of FUS-DDIT3 fusion genes. Therefore, the drug seems to induce a maturation of MLS lipoblasts, with transition of the residual spindle non-lipogenic cells into mature vacuolated lipoblasts. This effect could be prevented by the increase of leptin circulating levels in obese patients. For these reasons we designed this retrospective analysis in order to evaluate the BMI status (measure of total adipose content) as a pr…
PML expression in soft tissue sarcoma: Prognostic and predictive value in alkylating agents/antracycline-based first line therapy
Soft tissue sarcomas are aggressive tumors representing <1% of all adult neoplasms. Aim of our study was to evaluate promyelocytic leukemia gene expression value as prognostic factor and as a factor predicting response to alkylating agents/antracycline-based first line therapy. One hundred eleven patients affected by locally advanced and metastatic soft tissue sarcoma were selected. PML expression was evaluated by immunohistochemical analysis in pathological samples and in the corresponding normal tissue from each case. PML immunohistochemical results were correlated with prognosis and with radiological response to alkylating agents/antracycline-based first line therapy. PML expression was …
Familial adenomatosis polyposis-related desmoid tumours treated with low-dose chemotherapy: Results from an international, multi-institutional, retrospective analysis
[Introduction] Desmoid tumour (DT) is a locally aggressive fibroblastic proliferative disease representing the most common extraintestinal manifestation of familial adenomatosis polyposis (FAP). As data on the activity of chemotherapy in these patients are limited, we examined the outcomes of patients treated with low-dose methotrexate (MTX)+vinca alkaloids (vinorelbine or vinblastine).
PML down-regulation in soft tissue sarcomas
To date, little is known concerning the promyelocytic leukemia gene (PML) status in tumors of different origin, and its expression has never been evaluated in soft tissue sarcoma. The aim of the present study is focused on the identification of differences in terms of PML protein expression between different types of soft tissue sarcoma and the corresponding normal surrounding tissue. PML protein expression has been assessed by immunohistochemistry in six different histologic types of soft tissue sarcoma (synovial sarcoma, myofibroblastic sarcoma, angiosarcoma, liposarcoma, pleomorphic sarcoma, and leiomyosarcoma) and in the corresponding normal surrounding tissue. PML resulted significantl…
Advanced epithelioid haemangioendotelioma: Fever, pain, and pleural effusion predict a worse outcome.
e22540 Background: Epithelioid hemangioendothelioma (EHE) is an exceedingly rare soft tissue sarcoma subtype. EHE often presents as a multifocal/ multivisceral disease and its clinical behavior is highly unpredictable from indolent to very aggressive forms. A common choice in advanced patients is a close, active surveillance (AS), considering a treatment only in case of disease progression. Our retrospective study aimed to identify clinical features associated with a more aggressive behavior. Methods: Patients affected by advanced EHE treated in 6 centers of the Italian Rare Cancer Network were retrospectively reviewed. Diagnosis was confirmed by a sarcoma expert pathologist and molecular …
Adjuvant Imatinib in Patients with GIST Harboring Exon 9 KIT Mutations : Results from a Multi-institutional European Retrospective Study
[Purpose] The effect of high-dose imatinib (800 mg/day) on survival in the adjuvant treatment of patients with resected KIT exon 9–mutated gastrointestinal stromal tumors (GIST) is not established. Here, the association of dose and other clinicopathologic variables with survival was evaluated in a large multi-institutional European cohort.
Adverse events as potential predictive factors of activity in patients with advanced hepatocellular carcinoma treated with lenvatinib
Background and Aim: Lenvatinib is a standard of care option in first-line therapy of advanced hepatocellular carcinoma (HCC). In the present study, we aim to identify, in patients with HCC treated with lenvatinib, a possible association between occurrence and grading of adverse events (AEs) and outcome. Methods: We performed a retrospective analysis of 606 Japanese and Italian patients treated with lenvatinib in first-line setting and investigated the possible correlation between the onset of AEs, toxicity grade (G) and outcome measures such as overall survival (OS) and progression-free survival (PFS). Results: The appearance of arterial hypertension G ≥ 2 independently predicted prolonged …
Bone metastases in soft tissue sarcoma: a survey of natural history, prognostic value and treatment options
Abstract Background We surveyed the natural history of bone metastases in patients affected by soft tissue sarcoma (STS). Methods This multicenter retrospective observational study included 135 patients. Histological subtype, characteristics of bone metastases, treatment, skeletal related events (SREs) and disease outcome were recorded. Results The most represented histological subtypes were leiomyosarcoma (27%) angiosarcoma (13%) and undifferentiated sarcoma (8%). Axial skeleton was the most common site for bone involvement (70%). In 27% of cases, bone metastases were present at the time of diagnosis. Fifty-four (40%) patients developed SREs and the median time to first SRE was 4 months (r…
Clinical outcomes with atezolizumab plus bevacizumab or lenvatinib in patients with hepatocellular carcinoma: a multicenter real-world study
Purpose: The purpose of this study is to compare response rates of lenvatinib and atezolizumab plus bevacizumab, in first-line real-world setting. Methods: Overall cohort included Western and Eastern hepatocellular carcinoma (HCC) patient populations from 46 centres in 4 countries (Italy, Germany, Japan, and Republic of Korea). Results: 1312 patients were treated with lenvatinib, and 823 patients were treated with atezolizumab plus bevacizumab. Objective response rate (ORR) was 38.6% for patients receiving lenvatinib, and 27.3% for patients receiving atezolizumab plus bevacizumab (p < 0.01; odds ratio 0.60). For patients who achieved complete response (CR), overall survival (OS) was not …
Body Mass Index as a Risk Factor for Toxicities in Patients with Advanced Soft-Tissue Sarcoma Treated with Trabectedin
<b><i>Objectives:</i></b> Low body mass index (BMI) and/or low lean body mass have been shown to be risk factors for chemotherapy-related toxicities in a number of different cancers. However, no data are available regarding the role of BMI as a risk factor for developing toxicities related to the novel anticancer agent, trabectedin, in patients with soft-tissue sarcoma (STS). We evaluated the role of BMI as a risk factor for trabectedin-related toxicity in patients with STS. <b><i>Methods:</i></b> Data from 51 patients with metastatic/advanced STS treated with trabectedin after progression on ≥1 anthracycline ± ifosfamide regimen were retrospe…
Bone metastases in soft tissue sarcoma patients: A survey of natural, prognostic value, and treatment.
10063 Background: Given the limited data currently available, we surveyed the natural history of bone metastases in patients affected by soft tissue sarcoma (STS). Methods: This retrospective, multicenter, observational study evaluated data from 135 patients with STS metastatic to the bone who presented between 2001 and 2011. For all patients, we recorded the primary tumor histological subtype, bone metastases characteristics (onset, site), type of treatment received (surgery, radiotherapy, zoledronic acid), type and frequency of skeletal related events (SRE) and disease outcome. Results: The most represented histological subtypes among the enrolled patients were leiomyosarcoma (27%), angi…
Early magnesium reduction in advanced colorectal cancer patients treated with cetuximab plus irinotecan as predictive factor of efficacy and outcome
Abstract Introduction: Magnesium plays a role in a large number of cellular metabolic reactions. Cetuximab is able to induce hypomagnesemia by interfering with magnesium (Mg2+) transport in the kidney. We designed this trial to investigate if Mg2+ serum level modifications may be related with clinical response and outcome in advanced colorectal cancer patients during treatment with cetuximab plus irinotecan. Experimental Design: Sixty-eight heavily pretreated metastatic colorectal cancer patients were evaluated for Mg2+ serum levels at the following time points: before; 6 hours; and 1, 7, 14, 21, 50, and 92 days after the start of treatment. Results: Basal Mg2+ median levels were significan…
Trabectedin-Related Liver Toxicity in Soft Tissue Sarcoma Patients: Always a Good Reason to Discontinue the Treatment?
ABSTRACT Aim: A transient increase in liver enzymes is a well described side effect developed by almost 40% of soft tissue sarcoma (STS) patients treated with trabectedin, often leading to treatment delays or discontinuation. We retrospectively analysed the correlation between trabectedin-related liver toxicity and treatment outcome. Methods: Data from a total of 113 patients receiving trabectedin administered at the dose of 1.5 mg/m2 iv 24 hours in 3 reference centers were evaluated. This exploratory analysis was performed to assess the impact of liver toxicity (grade 3-4 AST and ALT increases) on the trabectedin efficacy and outcome in STS patients. All the patients included had metastati…
The changes of lipid metabolism in advanced renal cell carcinoma patients treated with everolimus: a new pharmacodynamic marker?
Background: Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved for the treatment of metastatic renal cell carcinoma (mRCC). We aimed to assess the association between the baseline values and treatmentrelated modifications of total serum cholesterol (C), triglycerides (T), body mass index (BMI), fasting blood glucose level (FBG) and blood pressure (BP) levels and the outcome of patients treated with everolimus for mRCC. Methods: 177 patients were included in this retrospective analysis. Time to progression (TTP), clinical benefit (CB) and overall survival (OS) were evaluated. Results: Basal BMI was significantly higher in patients who experienced a CB (p=0,0145). C, T an…
Use of Cardioprotective Dexrazoxane Is Associated with Increased Myelotoxicity in Anthracycline-Treated Soft-Tissue Sarcoma Patients
<b><i>Background:</i></b> Dexrazoxane (DEX) is indicated as a cardioprotective agent for breast cancer patients receiving the anthracycline doxorubicin. Two meta-analyses in metastatic breast cancer reported an apparent increase in the severity of myelosuppression when DEX was used. So far, no data in soft-tissue sarcoma (STS) patients are available. <b><i>Methods:</i></b> We retrospectively analyzed hematological toxicity data from 133 consecutive STS patients who received a chemotherapy regimen containing an anthracycline and ifosfamide (AI) in the perioperative or metastatic settings between January 2006 and December 2017. Of these, 46 rece…
Real-Life Clinical Data of Lenvatinib versus Sorafenib for Unresectable Hepatocellular Carcinoma in Italy
Valentina Burgio,1 Massimo Iavarone,2 Giovanni Giuseppe Di Costanzo,3 Fabio Marra,4 Sara Lonardi,5,6 Emiliano Tamburini,7 Fabio Piscaglia,8 Gianluca Masi,9,10 Ciro Celsa,11 Francesco Giuseppe Foschi,12 Marianna Silletta,13 Daniela Caterina Amoruso,14 Margherita Rimini,15 Mariangela Bruccoleri,2 Raffaella Tortora,3 Claudia Campani,4 Caterina Soldà ,6 Massimo Giuseppe Viola,16 Antonella Forgione,8 Fabio Conti,12 Francesca Salani,9,10 Silvia Catanese,9,10 Carmelo Marco Giacchetto,17 Claudia Fulgenzi,13 Carmine Coppola,14 Pietro Lampertico,18 Antonio Pellino,6,19 Gabriele Rancatore,17 Giuseppe Cabibbo,17 Francesca Ratti,20 Federica Pedica,21 Angelo Della Corte,22 Massimo Colombo,18 Francesco De…
Prognostic significance of circulating PD-1, PD-L1, pan-BTN3As and BTN3A1 in patients with metastatic gastrointestinal stromal tumours (mGISTs)
Abstract Background Gastrointestinal stromal tumours (GISTs) account for 1% of all primary gastrointestinal cancers. In cancer, suppressive immune checkpoints, including butyrophilin sub-family 3A/CD277 receptors (BTN3A), programmed death protein (PD-1) and its ligand PD-L1, are often hyper-activated to ensure an effective evasion of tumor cells from immune surveillance. Since recent studies showed that PD-1 and PD-L1 expression in cancer may be an important prognostic factor, the aim of our study was to investigate if soluble forms of inhibitory immune checkpoints can help predict survival in metastatic GIST patients. Methods Using specific homemade ELISA assays not yet commercially availa…
Lack of Correlation between Liver Tests Abnormalities and Trabectedin Efficacy in the Treatment of Soft Tissue Sarcoma: A Retrospective Study
AbstractElevation in liver transaminases is common in patients treated with the marine antitumor agent trabectedin. However, the impact of trabectedin-related transaminase elevations on treatment outcomes is unclear. This retrospective study investigated the correlation between liver tests abnormalities and treatment outcomes in patients with unresectable advanced or metastatic soft tissue sarcomas (STS) treated with trabectedin 1.5 mg/m2 once every 3 weeks at three reference centers in Italy. The effect of grade 3/4 elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) during the first two cycles and at any time during trabectedin treatment on progression-free su…
FAP-related desmoid tumours treated with low dose chemotherapy: Results from a multicentre retrospective analysis.
11556Background: Desmoid tumours (DTs) are monoclonal neoplasms with fibroblastic-myofibroblastic differentiation and they represent the most common extra-intestinal manifestation of familial adeno...
Nonalcoholic steatohepatitis in hepatocarcinoma: new insights about its prognostic role in patients treated with lenvatinib
Background Hepatocellular carcinoma (HCC) treatment remains a big challenge in the field of oncology. The liver disease (viral or not viral) underlying HCC turned out to be crucial in determining the biologic behavior of the tumor, including its response to treatment. The aim of this analysis was to investigate the role of the etiology of the underlying liver disease in survival outcomes. Patients and methods We conducted a multicenter retrospective study on a large cohort of patients treated with lenvatinib as first-line therapy for advanced HCC from both Eastern and Western institutions. Univariate and multivariate analyses were performed. Results Among the 1232 lenvatinib-treated HCC pat…
Prognostic Relevance of Objective Response According to EASL Criteria and mRECIST Criteria in Hepatocellular Carcinoma Patients Treated with Loco-Regional Therapies: A Literature-Based Meta-Analysis.
Background The European Association for the Study of the Liver (EASL) criteria and the modified Response Evaluation Criteria in Solid Tumors (mRECIST) are currently adopted to evaluate radiological response in patients affected by HCC and treated with loco-regional procedures. Several studies explored the validity of these measurements in predicting survival but definitive data are still lacking. Aim To conduct a systematic review of studies exploring mRECIST and EASL criteria usefulness in predictive radiological response in HCC undergoing loco-regional therapies and their validity in predicting survival. Methods A comprehensive search of the literature was performed in electronic database…
Recent Advances in Desmoid Tumor Therapy
The desmoid tumor is a locally aggressive proliferative disease within the family of soft-tissue sarcomas. Despite its relatively good prognosis, the clinical management of desmoid tumors requires constant multidisciplinary evaluation due to its highly variable clinical behavior. Recently, active surveillance has being regarded as the appropriate strategy at diagnosis, as indolent persistence or spontaneous regressions are not uncommon. Here, we review the most recent advances in desmoid tumor therapy, including low-dose chemotherapy and treatment with tyrosine kinase inhibitors. We also explore the recent improvements in our knowledge of the molecular biology of this disease, which are lea…