A randomized double-blind phase II study evaluating the role of maintenance therapy with cabozantinib in high-grade uterine sarcoma after stabilization or response to doxorubicin ± ifosfamide following surgery or in metastatic first line treatment (EORTC62113).

Funder: European Organisation for Research and Treatment of Cancer; FundRef: http://dx.doi.org/10.13039/501100004897Funder: Ligue Nationale de Lutte contre le Cancer (France)BACKGROUND: Uterine sarcomas are a group of rare tumors that include different subtypes. Patients with histopathological high-grade diseases are at high-risk of recurrence or progression, and have a poor prognosis. We aim to explore the most appropriate management in patients with uterine high-grade sarcomas. PRIMARY OBJECTIVE: To assess the efficacy of maintenance treatment with cabozantinib in patients with high-grade uterine sarcomas who achieved clinical benefit after standard chemotherapy. STUDY HYPOTHESIS: Maintenance treatment with cabozantinib after standard chemotherapy given as an adjuvant treatment after curative surgery, or in locally advanced or metastatic disease, increases progression-free survival compared with placebo TRIAL DESIGN: This is a randomized double blinded phase II trial. MAJOR INCLUSION/EXCLUSION CRITERIA: The study is enrolling adult patients with high-grade undifferentiated uterine sarcomas, high-grade endometrial stromal sarcomas, high-grade leiomyosarcoma, and high-grade adenosarcoma, FIGO (Federation International gynecologue Obstétricien) stage II/III to IV in stable disease or who achieved complete or partial response with doxorubicin ± ifosfamide, who are assigned 1:1 to 60 mg daily cabozantinib (experimental arm) or placebo (control arm), as maintenance therapy. Exclusion criteria include low-grade sarcoma. PRIMARY ENDPOINT: Progression-free survival at 4 months. SAMPLE SIZE: The study plans to enroll 90 patients to allow the randomization of 54 patients to detect an improvement in 4-month progression-free survival from 50% to 80% with 15% significance level and 85% power. Estimated dates for accrual completion: recruitment for the trial started in February 2015, and has currently enrolled 83 patients, of whom 35 patients have been randomized. The end of recruitment is anticipated for December 2020. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, number NCT01979393

Determinants of the access to remote specialised services provided by national sarcoma reference centres

BACKGROUND: Spatial inequalities in cancer management have been evidenced by studies reporting lower quality of care or/and lower survival for patients living in remote or socially deprived areas. NETSARC+ is a national reference network implemented to improve the outcome of sarcoma patients in France since 2010, providing remote access to specialized diagnosis and Multidisciplinary Tumour Board (MTB). The IGéAS research program aims to assess the potential of this innovative organization, with remote management of cancers including rare tumours, to go through geographical barriers usually impeding the optimal management of cancer patients. METHODS: Using the nationwide NETSARC+ databases, the individual, clinical and geographical determinants of the access to sarcoma-specialized diagnosis and MTB were analysed. The IGéAS cohort (n = 20,590) includes all patients living in France with first sarcoma diagnosis between 2011 and 2014. Early access was defined as specialised review performed before 30 days of sampling and as first sarcoma MTB discussion performed before the first surgery. RESULTS: Some clinical populations are at highest risk of initial management without access to sarcoma specialized services, such as patients with non-GIST visceral sarcoma for diagnosis [OR 1.96, 95% CI 1.78 to 2.15] and MTB discussion [OR 3.56, 95% CI 3.16 to 4.01]. Social deprivation of the municipality is not associated with early access on NETSARC+ remote services. The quintile of patients furthest away from reference centres have lower chances of early access to specialized diagnosis [OR 1.18, 95% CI 1.06 to 1.31] and MTB discussion [OR 1.24, 95% CI 1.10 to 1.40] but this influence of the distance is slight in comparison with clinical factors and previous studies on the access to cancer-specialized facilities. CONCLUSIONS: In the context of national organization driven by reference network, distance to reference centres slightly alters the early access to sarcoma specialized services and social deprivation has no impact on it. The reference networks' organization, designed to improve the access to specialized services and the quality of cancer management, can be considered as an interesting device to reduce social and spatial inequalities in cancer management. The potential of this organization must be confirmed by further studies, including survival analysis

Shortening the Time Interval for the Referral of Patients With Soft Tissue Sarcoma to Expert Centers Using Mobile Health: Retrospective Study

BackgroundAccording to guidelines, all patients with sarcoma must be managed from initial diagnosis at expert sarcoma centers. However, in everyday practice, the time interval to an expert center visit can be long, which delays presentation to an expert multidisciplinary tumor board and increases the risk of inappropriate management, negatively affecting local tumor control and prognosis. The advent of mobile health offers an easy way to facilitate communication and cooperation between general health care providers (eg, general practitioners and radiologists) and sarcomas experts. We developed a mobile app (Sar’Connect) based on the algorithm designed by radiologists from the French Sarcoma Group. Through a small number of easy-to-answer questions, Sar’Connect provides personalized advice for the management of patients and contact information for the closest expert center. ObjectiveThis retrospective study is the first to assess this mobile app’s potential benefits in reducing the time interval for patient referral to an expert center according to the initial clinical characteristics of the soft tissue tumor. MethodsFrom May to December 2021, we extracted tumor mass data for 78 patients discussed by the multidisciplinary tumor boards at 3 centers of the French Sarcoma Group. We applied the Sar’Connect algorithm to these data and estimated the time interval between the first medical description of the soft tissue mass and the referral to expert center. We then compared this estimated time interval with the observed time interval. ResultsWe found that the use of Sar’Connect could potentially shorten the time interval to an expert center by approximately 7.5 months (P<.001). Moreover, for half (31/60, 52%) of the patients with a malignant soft tissue tumor, Sar’Connect could have avoided inappropriate management outside of the reference center. We did not identify a significant determinant for shortening the time interval for referral. ConclusionsOverall, promoting the use of a simple mobile app is an innovative and straightforward means to potentially accelerate both the referral and management of patients with soft tissue sarcoma at expert centers

Circulating vascular endothelial growth factor (VEGF) as predictive factor of progression-free survival in patients with advanced chordoma receiving sorafenib: an analysis from a phase II trial of the french sarcoma group (GSF/GETO)

International audienceBackground: Patients with advanced chordoma are often treated with tyrosine kinase inhibitors without any predictive factor to guide decision. We report herein an ancillary analysis of the the Angionext phase II trial (NCT 00874874). Results: From May 2011 to January 2014, 26 were sampled. The 9-month PFS rate was 72.9% (95%-CI: 45.9-87.9). During sorafenib treatment, a significant increase in PlGF (18.4 vs 43.8 pg/mL, p1.04 ng/mL (HR=12.5, 95%-CI: 1.37-114, p=0.025) and VEGF at D7 >1.36 ng/mL (HR=10.7, 95%-CI: 1.16-98, p= 0.037) were associated with shorter PFS. The 9-month PFS rate was 92.3% (95%-CI: 56.6-98.9) when VEGF at D1 was 1.04 ng/mL. Patients and Methods: Chordoma patients were treated with sorafenib 800 mg/day for 9 months, unless earlier occurrence of progression or toxicities. Six biomarkers (sE-Selectin, VEGF, VEGF-C, placental growth factor (PlGF), Thrombospondin, Stem Cell Factor (SCF)) were measured at baseline (day 1: D1) and day 7 (D7). Conclusion: High levels of VEGF was associated with poor outcome

Initial FDG-PET/CT predicts survival in adults Ewing sarcoma family of tumors

International audienceCopyright: Jamet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Purpose: The aim of this retrospective study was to determine, at baseline, the prognostic value of different FDG-PET/CT quantitative parameters in a homogenous Ewing Sarcoma Family of Tumors (ESFT) adult population, compared with clinically relevant prognostic factors. Methods: Adult patients from 3 oncological centers, all with proved ESFT, were retrospectively included. Quantitative FDG-PET/CT parameters (SUV (maximum, peak and mean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of the primary lesion of each patient were recorded before treatment, as well as usual clinical prognostic factors (stage of disease, location, tumor size, gender and age). Then, their relation with progression free survival (PFS) and overall survival (OS) was evaluated. Results: 32 patients were included. Median age was 21 years (range, 15 to 61). Nineteen patients (59%) were initially metastatic. On multivariate analysis, high SUV max remained independent predictor of worst OS (p=0.02) and PFS (p=0.019), metastatic disease of worst PFS (p=0.01) and high SUVpeak of worst OS (p=0.01). Optimal prognostic cutoff of SUV peak was found at 12.5 in multivariate analyses for PFS and OS (p=0.0001). Conclusions: FDG-PET/CT, recommended at ESFT diagnosis for initial staging, can be a useful tool for predicting long-term adult patients outcome through semi-quantitative parameters

Prognostic and predictive factors for angiosarcoma patients receiving paclitaxel once weekly plus or minus bevacizumab: an ancillary study derived from a randomized clinical trial

Abstract Background We report here a correlation analysis conducted along with a phase II trial assessing bevacizumab in combination with weekly paclitaxel. Methods Circulating pro/anti-angiogenic factors were assessed on day 1 (D1) and day 8 (D8). The prognostic value for progression-free survival (PFS) was evaluated using a Cox model with biomarkers as continuous variables. Results Among the 51 patients enrolled and treated in this trial, biomarker analysis was performed for 42: 18 in Arm A (single-agent) and 24 in Arm B (combination). With a median follow-up of 46 months, PFS was 5.5 versus 5.7 months, respectively (p = 0.75). According to univariate analysis, factors associated with a poor PFS were as follows: visceral angiosarcoma, de novo angiosarcoma, and high PlGF and low VEGF-C baseline values. In multivariate analysis, de novo angiosarcoma (HR = 2.5; p = 0.024) and baseline VEGF-C value (HR = 0.7; p = 0.003) were significant prognostic factors. We observed a significant increase in circulating PlGF (< 0.001) and a decrease in VEGF (< 0.001) during bevacizumab treatment. An increase in FGF was associated with a poor outcome. Conclusions De novo angiosarcoma and a low baseline level of VEGF-C were found to be associated with a poor prognosis. Addition of bevacizumab induces major changes in circulating biomarkers (VEGF and PlGF) in a short timeframe without impacting PFS. Trial registration Retrospectively registered on EudraCT N° 2009–017020-59 and NCT01303497 (February 24, 2011)

Phase II study of figitumumab in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck : clinical activity and molecular response (GORTEC 2008-02)

BACKGROUND: Preclinical studies suggest that insulin-like growth factor-1 receptor (IGF-1R) blockage could be a promising therapeutic target in squamous cell carcinoma of the head and neck (SCCHN). Therefore, we investigated the efficacy and toxicity of figitumumab, an anti-IGF-1R monoclonal antibody, in palliative SCCHN. PATIENTS AND METHODS: Patients with palliative SCCHN progressing after platinum-based therapy were treated with figitumumab i.v. 20 mg/kg, every 3 weeks. The primary end point was the disease control rate at 6-8 weeks after treatment initiation. Tumor biopsies and plasma samples were collected before and after figitumumab administration to monitor the molecular response. RESULTS: Seventeen patients were included. Only two patients achieved stable disease at 6-8 weeks. Median overall survival and progression-free survival were 63 and 52 days, respectively. The main grade 3-4 adverse event was hyperglycemia (41%). Translational research showed that figitumumab downregulated IGF-1R at the surface of tumor cells with activation of the epidermal growth factor receptor (EGFR) pathway, as shown by the upregulation of p-EGFR in tumor cells (P = 0.016), and an increase in the plasma level of tumor growth factor-alpha (P = 0.006). CONCLUSION: Figitumumab monotherapy has no clinically significant activity in unselected palliative SCCHN

Recombinant erythropoietin for the anaemia of patients with advanced Gastrointestinal Stromal Tumours (GIST) receiving imatinib: an active agent only in non progressive patients

<p>Abstract</p> <p>Recombinant erythropoietin for the anaemia of patients with advanced Gastrointestinal Stromal Tumours (GIST) receiving imatinib : an active agent only in non progressive patients.</p> <p>Background</p> <p>Imatinib is a standard treatment for advanced/metastatic GIST and in adjuvant setting. Anaemia is frequently observed in patients with advanced GIST, and is one of the most frequent side effects of imatinib with grade 3–4 anaemia in 10% of patients. Whether EPO treatment is useful in the management of GIST patients receiving imatinib treatment is unknown.</p> <p>Methods</p> <p>A retrospective study of EPO treatment in GIST patients receiving imatinib was undertaken in 4 centres. Thirty four patients received EPO treatment among the 319 GIST patients treated with imatinib in clinical trials or with compassionate use between 2001 and 2003. The efficacy of EPO on the anaemia of patients with GIST treated with imatinib was analyzed.</p> <p>Results</p> <p>There were 18 males and 16 females with a median age of 59 years. Median WHO-PS was 1. Primary tumour sites were mainly gastric (32%) and small bowel (29%). Sites of metastases were mainly liver (82%) and peritoneum (79%). The median delay between the initiation of imatinib treatment and EPO was 58 days (range 0–553). Median haemoglobin (Hb) level prior to EPO was 9 g/dL (range 6,9-11,8) and 11,7 g/dL (range 6,8-14,4) after 2 months. An increase of more than 2 g/dL was observed in 18 (53%) of patients. None of the 7 patients who progressed (PD) under imatinib treatment (400 mg/day) experienced HB response, as compared to 66% (18/27) of the remaining patients (PR + SD) (p = 0,002). Primary tumour site, liver metastases, peritoneal metastases, age, gender did not correlate with HB response to EPO. Response to EPO was observed in 2/11 patients receiving high-dose imatinib (800 mg/day) <it>vs</it> 16/23 of others. Using logistic regression, only PD before EPO treatment was retained as a predictive factor for EPO response.</p> <p>Conclusion</p> <p>EPO enables to increase Hb in most anaemic GIST patients who do not progress under imatinib, but not in patients with progressive disease.</p

Pazopanib plus best supportive care versus best supportive care alone in advanced gastrointestinal stromal tumours resistant to imatinib and sunitinib (PAZOGIST): a randomised, multicentre, open-label phase 2 trial

International audienc