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Background: Isolated limb perfusion (ILP) is a well-established surgical procedure for the administration of high dose chemotherapy to a limb for the treatment of advanced extremity malignancy. Although the technique of ILP was first described over 60 years ago, ILP is utilised in relatively few specialist centres, co-located with tertiary or quaternary cancer centres. The combination of high dose cytotoxic chemotherapy and the cytokine tumour necrosis factor alpha (TNFα), mandates leakage monitoring to prevent potentially serious systemic toxicity. Since the procedure is performed at relatively few specialist centres, an ILP working group was formed with the aim of producing technical consensus guidelines for the procedure to streamline practice and to provide guidance for new centres commencing the technique., Methods: Between October 2021 and October 2023 a series of face to face online and hybrid meetings were held in which a modified Delphi process was used to develop a unified consensus document. After each meeting the document was modified and recirculated and then rediscussed at subsequent meeting until a greater than 90% consensus was achieved in all recommendations., Results: The completed consensus document comprised 23 topics in which greater than 90% consensus was achieved, with 83% of recommendations having 100% consensus across all members of the working group. The consensus recommendations covered all areas of the surgical procedure including pre-operative assessment, drug dosing and administration, perfusion parameters, hyperthermia, leakage monitoring and theatre logistics, practical surgical strategies and also post-operative care, response evaluation and staff training., Conclusion: We present the first joint expert-based consensus statement with respect to the technical aspects of ILP that can serve as a reference point for both existing and new centres in providing ILP., Competing Interests: Declaration of competing interest Angela Märten works as a consultant for Belpharma SA., (© 2024 Published by Elsevier Ltd.)

Objective: To update the current Sarculator retroperitoneal sarcoma (RPS) prognostic nomograms considering the improvement in patient prognosis and the case volume effect., Background: Survival of patients with primary RPS has been increasing over time, and the volume-outcome relationship has been well recognized. Nevertheless, the specific impact on prognostic nomograms is unknown., Methods: All consecutive adult patients with primary localized RPS treated at 8 European and North American sarcoma reference centers between 2010 and 2017 were included. Patients were divided into 2 groups: high-volume centers (HVC, ≥13 cases/year) and low-volume centers (LVC, <13 cases/year). Primary end points were overall survival (OS) and disease-free survival (DFS). Multivariable analyses for OS and DFS were performed. The nomograms were updated by recalibration. Nomograms performance was assessed in terms of discrimination (Harrell C index) and calibration (calibration plot)., Results: The HVC and LVC groups comprised 857 and 244 patients, respectively. The median annual primary RPS case volume (interquartile range) was 24.0 in HVC (15.0-41.3) and 9.0 in LVC (1.8-10.3). Five-year OS was 71.4% (95% CI: 68.3%-74.7%) in the HVC cohort and 63.3% (56.8%-70.5%) in the LVC cohort ( P =0.012). Case volume was associated with both OS (LVC vs. HVC hazard ratio 1.40, 95% CI: 1.08-1.82, P =0.011) and DFS (hazard ratio 1.93, 95% CI: 1.57-2.37, P <0.001) at multivariable analyses. When applied to the study cohorts, the Sarculator nomograms showed good discrimination (Harrell C index between 0.68 and 0.73). The recalibrated nomograms showed good calibration in the HVC group, whereas the original nomograms showed good calibration in the LVC group., Conclusions: New nomograms for patients with primary RPS treated with surgery at high-volume versus low-volume sarcoma reference centers are available in the Sarculator app., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Whether re-excision (RE) of a soft tissue sarcoma (STS) of limb or trunk should be systematized as adjuvant care and if it would improve metastatic free survival (MFS) are still debated. The impact of resection margins after unplanned macroscopically complete excision (UE) performed out of a NETSARC reference center or after second resection was further investigated., Methods: This large nationwide series used data from patients having experienced UE outside of a reference center from 2010 to 2019, collected in a French nationwide exhaustive prospective cohort NETSARC. Patient characteristics and survival distributions in patients reexcised (RE) or not (No-RE) are reported. Multivariate Cox proportional hazard model was conducted to adjust for classical prognosis factors. Subgroup analysis were performed to identify which patients may benefit from RE., Results: Out of 2371 patients with UE for STS performed outside NETSARC reference centers, 1692 patients were not reviewed by multidisciplinary board before treatment decision and had a second operation documented. Among them, 913 patients experienced re-excision, and 779 were not re-excised. Characteristics were significantly different regarding patient age, tumor site, size, depth, grade and histotype in patients re-excised (RE) or not (No-RE). In univariate analysis, final R0 margins are associated with a better MFS, patients with R1 margins documented at first surgery had a better MFS as compared to patients with first R0 resection. The study identified RE as an independent favorable factor for MFS (HR 0.7, 95% CI 0.53-0.93; p = 0.013). All subgroups except older patients (>70 years) and patients with large tumors (>10 cm) had superior MFS with RE., Conclusions: RE might be considered in patients with STS of limb or trunk, with UE with macroscopic complete resection performed out of a reference center, and also in originally defined R0 margin resections, to improve LRFS and MFS. Systematic RE should not be advocated for patients older than 70 years, or with tumors greater than 10 cm.

Desmoid tumors (DT) are rare, slow-growing, locally invasive soft tissue tumors that often pose significant therapeutic challenges. Traditional management strategies including active surveillance, surgery, radiotherapy, and systemic therapy which are associated with varying recurrence rates and high morbidity. Given the challenging nature of DT and the modest outcomes associated with current treatment strategies, there has been a growing interest in the field of γ-secretase inhibitors as a result of its action on the Wnt/β-catenin signaling pathway. In this review article, we will shed the light on the pathogenesis and molecular biology of DT, discuss its symptoms and diagnosis, and provide a comprehensive review of the traditional therapeutic approaches. We will also delve into the mechanisms of action of γ-secretase inhibitors, its efficacy, and the existing preclinical and clinical data available to date on the use of these agents, as well as the potential challenges and future prospects in the treatment landscape of these tumors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Whether "gurus", "emperor" or "influencers", wine consumers need references to help them choosing and buying wines. Given the diversity of possible sources (reviews from wine guides, wine merchants'recommendations or back wine label), where should they turn? Are all wine experts consensual in the way they taste wines? Do they differ depending on their domain of expertise: wine makers, sellers, or critics? This study aimed at understanding how experts apprehend wine tasting in relation to their professional objectives. A mixed design strategy combining content analysis of personal narratives of renowned wine experts with semi-structured interviews of wine professionals was used. Results confirmed that wine experts shared a common way of tasting wines, although their objectives and the way they report their wine tasting experiences differ according to their professional activities. Makers transcribe their perceptions by a list of sensory and technical-based terms focused on the absence or presence of wine defects to assess technical acceptability, Sellers are storytellers generating appeal and pleasure for consumers, and Critics write positive and metaphoric reviews to better highlight the best samples they taste. This raises new questions for the industry about the way in which wines are tasted, a routine practice that is internationally followed by wine professionals, but which may need to be renewed. Combining different data sources appeared to be a promising way to gain in-depth information in exploratory research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Sclerosing Epithelioid Fibrosarcoma (SEF) and Low Grade Fibromyxoid Sarcoma (LGFMS) are ultrarare sarcomas sharing common translocations whose natural history are not well known. We report on the nationwide exhaustive series of 330 patients with SEF or LGFMS in NETSARC+ since 2010., Patients and Methods: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDTB). Since 2010, (i) pathological review has been mandatory for sarcoma,and (ii) tumour/patients' characteristics have been collected in the NETSARC+ nationwide database. The characteristics of patients with SEF and LGFMS and their outcome are compared., Results: 35/73 (48%) and 125/257(49%) of patients with SEF and LGFMS were female. More visceral, bone and trunk primary sites were observed in SEF (p < 0.001). 30% of SEF vs 4% of LGFMS patients had metastasis at diagnosis (p < 0.0001). Median size of the primary tumor was 51 mm (range 10-90) for LGFMS vs 80 (20-320) for SEF (p < 0.001). Median age for LGFMS patients was 12 years younger than that of SEF patients (43 [range 4-98] vs 55 [range 10-91], p < 0.001). Neoadjuvant treatment was more often given to SEF (16% vs 9%, p = 0.05). More patients with LGFMS were operated first in reference centers (51% vs 26%, p < 0.001). The R0 rate on the operative specimen was 41% in LGFMS vs 16% in SEF (p < 0.001). Median event-free survival (EFS) of patients with SEF and LGFMS were 32 vs 136 months (p < 0.0001). The median overall survival (OS) was not reached. Fifty-months OS was 93% vs 81% for LGFMS vs SEF (p = 0.05). Median OS was 77 months after first relapse, similar for SEF and LGFMS. In multivariate analysis, age, tumor size, metastasis at diagnosis were independent prognostic factors for OS in LGFMS., Conclusions: Although sharing close molecular alterations, SEF and LGFMS have a different natural history, clinical presentation and outcome, with a higher risk of metastatic relapse in SEF. Survival after relapse is longer than with other sarcomas, and similar for SEF and LGFMS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Surgical resection is the current standard of care for retroperitoneal sarcoma (RPS). Recent data suggests that up to 5% of patient have incomplete (R2) resection. The exact reason why patients scheduled for surgery with a curative intent to treat ended up with an R2 resection is largely unknown., Aim of the Study: To identify intraoperative findings responsible for incomplete (R2) resection in primary RPS., Methods: All records of consecutive patients scheduled for a non-metastatic primary RPS surgery between 1995 and 2020 in a tertiary care sarcoma centre were retrospective analyzed., Results: Among the 347 patients scheduled for surgery, 13 (3.7%) had an incomplete (R2) resection. The reasons for incomplete surgery were intraoperative finding of vascular involvement of great vessels in 5 patients, previously undetected peritoneal metastases in 5 patients, invasion of contralateral kidney/ureter in 2 patients and the need to preserve both kidneys in 1 patient because of his past medical history. Among these patients, 3 had a laparotomy without resection and 10 had a partial resection (i.e. debulking surgery). Severe postoperative complications occurred in 5 patients. The median length of stay in hospital was 19days. After a median follow-up of 12months, the median survival of patients after incomplete resection was 18months. The 1-y, 5-y and 8-y overall survival (OS) for these patients were 46%, 14%, and 7%, respectively., Conclusion: Incomplete (R2) resection for a primary RPS surgery is rare in specialized sarcoma center. The next steps should be to identify the preoperative criteria that lead to this accurate selection and to define the best practice in front of a peroperative discovery of an unresectable RPS., Level of Evidence: III., (Copyright © 2023. Published by Elsevier Masson SAS.)

Opinion Statement: The therapeutic approach of pleomorphic liposarcoma (PLPS), a rare high-grade subgroup of soft tissue sarcoma, is commonly extrapolated from the management of other LPS subtypes. Only published retrospective data on PLPS currently serve as a guide for oncologists without clear recommendations or specific guidelines. In the advanced setting, specific systemic therapy such as eribulin and trabectedin showed promising activity in comparison to conventional therapy (doxorubicin- and gemcitabine-based protocols), which currently remains the current standard of care at initial stages of the disease. The better understanding of soft tissue sarcoma (STS) pathophysiology and disease course has led to the development of adapted clinical trial designs for rare STS histotypes with specific treatment approach., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This article presents the design, implementation, and first data of a uniquely flexible, multi-channel, frequency comb Doppler backscattering diagnostic recently made operational in the ASDEX-Upgrade tokamak [A. Gruber and O. Gruber, Fusion Sci. Technol. 44, 569 (2003)]. It uses a double side-band signal fed into a ×6 frequency multiplier to produce a multiple-frequency output spectrum. Seven of these frequencies are simultaneously measured in the receiver via a two-step frequency down-conversion and traditional I/Q demodulation. The frequency comb spectrum is fully tunable to sit anywhere in the W-band. The inter-frequency separation is also uniquely tunable remotely between 0.1 and 6 GHz without any hardware changes. The diagnostic can be operated in both O and X-mode polarizations and at both oblique and normal incidence to the cutoff layer. The time evolution of backscattered signals, in excess of 30 dB, from seven distinct frequencies sampled simultaneously is presented across an L-to-H-mode confinement regime transition., (© 2023 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).)

Objective: The aim of the present study was to compare the effect of radiotherapy (RT) on abdominal recurrence-free survival (ARFS) in patients with primary retroperitoneal sarcoma treated in the EORTC-STBSG-62092 (STRASS) phase 3 randomized controlled trial (STRASS cohort) and off-trial (STREXIT cohort) and to pool STRASS and STREXIT data to test the hypothesis that RT improves ARFS in patients with liposarcoma., Background: The STRASS trial did not show any difference in ARFS between patients treated with preoperative radiotherapy+surgery (RT+S) versus surgery alone (S)., Methods: All consecutive adult patients not enrolled in STRASS and underwent curative-intent surgery for a primary retroperitoneal sarcoma with or without preoperative RT between 2012 and 2017 (STRASS recruiting period) among ten STRASS-recruiting centres formed the STREXIT cohort. The effect of RT in STREXIT was explored with a propensity score (PS)-matching analysis. Primary endpoint was ARFS defined as macroscopically incomplete resection or abdominal recurrence or death of any cause, whichever occurred first., Results: STRASS included 266 patients, STREXIT included 831 patients (727 after excluding patients who received preoperative chemotherapy, 202 after 1:1 PS-matching). The effect of RT on ARFS in STRASS and 1:1 PS-matched STREXIT cohorts, overall and in patients with liposarcoma, was similar. In the pooled cohort analysis, RT administration was associated with better ARFS in patients with liposarcoma [N=321, hazard ratio (HR), 0.61; 95% confidence interval (CI), 0.42-0.89]. In particular, patients with well-differentiated liposarcoma and G1-2 dedifferentiated liposarcoma (G1-2 DDLPS, n=266) treated with RT+S had better ARFS (HR, 0.63; 95% CI, 0.40-0.97) while patients with G3 DDLPS and leiomyosarcoma had not. At the current follow-up, there was no association between RT and overall survival or distant metastases-free survival., Conclusions: In this study, preoperative RT was associated with better ARFS in patients with primary well-differentiated liposarcoma and G1-2 DDLPS., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate the outcomes of adult patients with spermatic cord sarcoma (SCS)., Methods: All consecutive patients with SCS managed by the French Sarcoma Group from 1980 to 2017 were analysed retrospectively. Multivariate analysis (MVA) was used to identify independent correlates of overall survival (OS), metastasis-free survival (MFS), and local relapse-free survival (LRFS)., Results: A total of 224 patients were recorded. The median age was 65.1 years. Forty-one (20.1%) SCSs were discovered unexpectedly during inguinal hernia surgery. The most common subtypes were liposarcoma (LPS) (73%) and leiomyosarcoma (LMS) (12.5%). The initial treatment was surgery for 218 (97.3%) patients. Forty-two patients (18.8%) received radiotherapy, 17 patients (7.6%) received chemotherapy. The median follow-up was 5.1 years. The median OS was 13.9 years. In MVA, OS decreased significantly with histology (HR, well-differentiated LPS versus others = 0.096; p = 0.0224), high grade (HR, 3 versus 1-2 = 2.7; p = 0.0111), previous cancer and metastasis at diagnosis (HR = 6.8; p = 0.0006). The five-year MFS was 85.9% [95% CI: 79.3-90.6]. In MVA, significant factors associated with MFS were LMS subtype (HR = 4.517; p < 10-4) and grade 3 (HR = 3.664; p < 10-3). The five-year LRFS survival rate was 67.9% [95% CI: 59.6-74.9]. In MVA, significant factors associated with local relapse were margins and wide reresection (WRR) after incomplete resection. OS was not significantly different between patients with initial R0/R1 resection and R2 patients who underwent WRR., Conclusions: Unplanned surgery affected 20.1% of SCSs. A nonreducible painless inguinal lump should suggest a sarcoma. WRR with R0 resection achieved similar OS to patients with correct surgery upfront., Competing Interests: Declaration of competing interest The authors have NO conflict of interest., (Copyright © 2023 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Desmoplastic small round cell tumor is a very rare and highly aggressive soft tissue sarcoma, usually presenting with multiple intra-abdominal tumors in young males. Patients present with advanced disease and the overall survival is dismal. Multiple studies report relatively favorable outcomes with multimodal treatment consisting of chemotherapy, surgery and radiotherapy. If resection is feasible, complete cytoreductive surgery is the cornerstone of surgical treatment. The benefit of hyperthermic intraperitoneal chemotherapy in addition to cytoreductive surgery is unclear, and few studies have evaluated this option. We sought to identify the role of hyperthermic intraperitoneal chemotherapy in patients with intra-abdominal desmoplastic small round cell tumor. Our review of the available literature revealed no clear survival benefit in performing hyperthermic intraperitoneal chemotherapy after cytoreductive surgery.

Objectives: Synovial sarcomas (SS) of the extremities are rare soft tissue sarcomas that are more common in young adults. We deciphered the imaging phenotype of SS with the aim to determine if imaging could provide an incremental value to currently known prognostic factors (PF)-age and histological grade-to predict long-term overall survival (OS)., Methods: This retrospective multicenter study included consecutive pediatric and adult patients with synovial sarcomas of the extremities from December 2002 to August 2020. Inclusion criteria were (i) a follow-up greater than 5 years and (ii) available pre-therapeutic MRI. A subset analysis included MRI and CT-scan. Clinical, pathological, and imaging variables were collected in all patients. The primary endpoint was to evaluate the association of these variables with OS using univariate and multivariate Cox regressions., Results: Out of 428 patients screened for eligibility, 98 patients (mean age: 37.1 ± 15.2 years) were included (MRI: n = 98/98, CT scan: n = 34/98; 35%). The median OS was 75.25 months (IQR = 55.50-109.12) and thirty-six patients (n = 36/98;37%) died during follow-up. The recurrence rate was 12.2% (n =12/98). SS lesions were mostly grade 2 (57/98; 58%). On MRI, SS had a mean long-axis diameter of 67.5 ± 38.3 mm. On CT scan, 44% (15/34) were calcified. Grade (hazard ratio [HR] = 2.71; 95%CI = 1.30-5.66; p = 0.008), size of the lesions evaluated on MRI (HR = 1.02; 95% CI = 1.01-1.03; p < 0.001), and calcifications on CT scan (HR = 0.10; 95% CI = 0.02-0.50; p = 0.005) were independent PF of OS., Conclusions: This study demonstrated that imaging biomarkers can be used to predict long-term outcome in patients with SS. Strikingly, the presence of calcifications on CT scan is associated with favorable outcome and provides an incremental value over existing PF such as age, grade, and size., Key Points: • Beyond its diagnostic value, MRI is a pre-operative prognostic tool in synovial sarcomas of the extremities since the size of the lesion is an important prognostic factor. • Calcifications on CT scans are independently and significantly associated with prolonged overall survival., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Gemcitabine has shown clinical activity against angiosarcoma in small series, alone, or combined with taxanes. We aimed to evaluate its activity as a single-agent in a larger series of patients with advanced angiosarcoma. We retrospectively reviewed the electronic medical records of consecutive adult patients with advanced angiosarcoma treated with single-agent gemcitabine at our institutions from January 2010 to January 2021. Response was evaluated according to RECIST 1.1, and toxicity was graded according to NCI-CTC v5.0. 42 patients were identified. 38 patients (90%) had received prior anthracyclines and weekly paclitaxel, and 9 (21%) had received pazopanib. The best tumor response was partial response (PR) in 16 patients (38%), or stable disease (10 patients, 24%). All 8 patients with cardiac angiosarcoma experienced a PR. Median PFS was 5.4 months (95%CI: 3.1-6.5), and median OS was 9.9 months (95%CI: 6.6-13.4). Single-agent gemcitabine has clinically meaningful activity in advanced, heavily pre-treated angiosarcoma., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: The initial management of patients with sarcoma is a critical issue. We used the nationwide French National Cancer Institute-funded prospective sarcoma database NETSARC to report the management and oncologic outcomes in adolescents and young adults (AYAs) patients with sarcoma at the national level., Patients and Methods: NETSARC database gathers regularly monitored and updated data from patients with sarcoma. NETSARC was queried for patients (15-30 years) with sarcoma diagnosed from 2010 to 2017 for whom tumor resection had been performed. We reported management, locoregional recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS) in AYA treated in French reference sarcoma centers (RSC) and outside RSC (non-RSC) and conducted multivariable survival analyses adjusted for classical prognostic factors., Results: Among 3,227 patients aged 15-30 years with sarcoma diagnosed between 2010 and 2017, the study included 2,227 patients with surgery data available, among whom 1,290 AYAs had been operated in RSC, and 937 AYAs in non-RSC. Significant differences in compliance to guidelines were observed including pre-treatment biopsy (RSC: 85.9%; non-RSC 48.1%), pre-treatment imaging (RSC: 86.8%; non-RSC: 56.5%) and R0 margins (RSC 57.6%; non-RSC: 20.2%) (p < 0.001). 3y-OS rates were 81.1% (95%CI 78.3-83.6) in AYA in RSC and 82.7% (95%CI 79.4-85.5) in AYA in non-RSC, respectively. Whereas no significant differences in OS was observed in AYAs treated in RSC and in non-RSC, LRFS and PFS were improved in AYAs treated in RSC compared to AYAs treated in non-RSC (Hazard Ratios (HR): 0.58 and 0.83, respectively)., Conclusions: This study highlights the importance for AYA patients with sarcoma to be managed in national sarcoma reference centers involving multidisciplinary medical teams with paediatric and adult oncologists., (© 2023. The Author(s).)

Background: This French nationwide NETSARC exhaustive prospective cohort aims to explore the impact of systematic re-excision (RE) as adjuvant care on overall survival (OS), local recurrence free survival (LRFS), and local and distant control (RFS) in patients with soft tissue sarcoma (STS) with positive microscopic margins (R1) after initial resection performed outside of a reference center., Methods: Eligible patients had experienced STS surgery outside a reference center from 2010 to 2017, and had R1 margins after initial surgery. Characteristics and treatment comparisons used chi-square for categorical variables and Kruskall-Wallis test for continuous data. Survival distributions were compared in patients reexcised (RE) or not (No-RE) using a log-rank test. A Cox proportional hazard model was used for subgroup analysis., Results: A total of 1,284 patients had experienced initial STS surgery outside NETSARC with R1 margins, including 1,029 patients with second operation documented. Among the latter, 698 patients experienced re-excision, and 331 were not re-excised. Characteristics were significantly different regarding patient age, tumor site, tumor size, tumor depth, and histotype in the population of patients re-excised (RE) or not (No-RE). The study identified RE as an independent favorable factor for OS (HR 0.36, 95%CI 0.23-0.56, p<0.0001), for LRFS (HR 0.45, 95%CI 0.36-0.56, p<0.0001), and for RFS (HR 0.35, 95%CI 0.26-0.46, p<0.0001)., Conclusion: This large nationwide series shows that RE improved overall survival in patients with STS of extremities and trunk wall, with prior R1 resection performed outside of a reference center. RE as part of adjuvant care should be systematically considered., (© 2022. The Author(s).)

Background: Acute abdominal complications (AAC) in patients with deep neutropenia (DN) is challenging to manage because of the expected influence of AAC on oncological prognosis and higher surgical complication rate in a period of DN. In practice, these parameters are difficult to appreciate. This study reported our experience in managing these patients., Methods: All consecutive patients treated in our tertiary care cancer center between 2010 and 2020 who developed AAC in the context of a DN were retrospectively analyzed. AAC was defined as an infection (intra-abdominal, perineal, or cutaneous), bowel obstruction, or intra-abdominal hemorrhage., Findings: Among 105 patients, 18 (17%) required emergent surgery (group 1), 34 patients had a complication requiring surgical oversight (group 2), and 53 patients had a non-surgical etiology (group 3). Fifteen patients underwent surgery in the group 1, three in group 2, and one in group 3. Overall, 28 patients died during hospitalization. Mortality was statistically different between the groups (p = 0·01), with a higher rate in group 1 (n = 9/18, 50%) than in group 2 (n = 11/34, 32%) and group 3 (n = 8/53, 15%). All groups together had a median overall survival (OS) of 14 months and disease-free survival (DFS) of 10 months. OS was not comparable between the groups, and the median length of survival in group 1 was 6 months versus 8 months in group 2 and 23 months in group 3. In group 1, five patients (5/18, 28%) did not relapse at the end of the follow-up compared to 13 in group 2 (13/34, 38%) and 25 in group 3 (25/53, 47%). After discharge, OS and DFS were similar between the groups., Interpretation: The advent of an AAC necessitating surgery in the context of DN is a deadly event associated with a 50% mortality; nonetheless, in case of unpostponable emergencies, surgery can provide long-term survival in selected patients., (© 2022. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

The national reference network NETSARC+ provides remote access to specialized diagnosis and the Multidisciplinary Tumour Board (MTB) to improve the management and survival of sarcoma patients in France. The IGéAS research program aims to assess the potential of this innovative organization to address geographical inequalities in cancer management. Using the IGéAS cohort built from the nationwide NETSARC+ database, the individual, clinical, and geographical determinants of the 3-year overall survival of sarcoma patients in France were analyzed. The survival analysis was focused on patients diagnosed in 2013 (n = 2281) to ensure sufficient hindsight to collect patient follow-up. Our study included patients with bone (16.8%), soft-tissue (69%), and visceral (14.2%) sarcomas, with a median age of 61.8 years. The overall survival was not associated with geographical variables after adjustment for individual and clinical factors. The lower survival in precarious population districts [HR 1.23, 95% CI 1.02 to 1.48] in comparison to wealthy metropolitan areas (HR = 1) found in univariable analysis was due to the worst clinical presentation at diagnosis of patients. The place of residence had no impact on sarcoma patients' survival, in the context of the national organization driven by the reference network. Following previous findings, this suggests the ability of this organization to go through geographical barriers usually impeding the optimal management of cancer patients.

Background: The prognosis of patients with advanced soft-tissue sarcomas (STS) remains dismal, and systemic therapeutic options are limited. Early phase trials are becoming increasingly safe and effective. This study aimed to identify the prognostic factors for progression-free survival (PFS)., Patients and Methods: This retrospective analysis included all STS patients participating in early phase trials at Gustave Roussy and Léon Bérard between 1 January 2012 and 31 December 2020., Results: Overall, 199 patients accounted for 214 inclusions in advanced STS. The most frequent histotypes were well-differentiated/dedifferentiated liposarcomas (n = 55), leiomyosarcomas (n = 53), synovial sarcomas (n = 22), undifferentiated pleomorphic sarcomas (n = 15), angiosarcomas (n = 12), and myxoid liposarcomas (n = 10). The median PFS was 2.8 months (95% confidence interval 2.7-4.1 months). The median PFS in the first, second, and later lines was 8.3, 5.4, and 2.6 months, respectively (P = 0.00015). The median PFS was 2.8 months in case of molecular screening, 4.1 months in case of histology-driven screening, and 1.6 months (P = 0.00014) in the absence of either screening modalities. In univariate analysis, histotype (P = 0.026), complex genomics (P = 0.008), number of prior lines (P < 0.001), prior anthracyclines (P < 0.001), number of metastatic sites (P = 0.003), liver metastasis (P < 0.001), lung metastasis (P < 0.001), absence of molecular or histology-driven screening (P < 0.001), first-in-human trials (P < 0.001), dose-escalation cohorts (P = 0.011), and Royal Marsden Hospital (RMH) score >1 (P < 0.001) were significantly associated with shorter PFS. In multivariate analysis, independent prognostic factors for shorter PFS were myxoid liposarcoma (P = 0.031), ≥2 prior lines of treatment (P = 0.033), liver metastasis (P = 0.007), and RMH score >2 (P = 0.006). Factors associated with improved PFS were leiomyosarcomas (P = 0.010), molecular screening (P = 0.025), and histology-driven screening (P = 0.010). The median overall survival rates were 36.3, 12.6, and 9.2 months in the first, second, and later lines, respectively (P = 0.0067). The grade 3-4 toxicity rate was 36%., Conclusions: Early phase trials provide an active therapeutic option for STS, even in first-line settings. Molecular screening and histology-driven trials further improve the clinical benefit., Competing Interests: Disclosure J-YB declares research support and honoraria from Bayer, Roche, Deciphera, Novartis, and GSK. OM has received consultancy fees from Amgen, AstraZeneca, Bayer, Blueprint Medicines, Bristol-Myers Squibb, Eli Lilly, Ipsen, Lundbeck, Merck Sharpe & Dohme, Pfizer, Roche, Servier, and Vifor Pharma. PP reports consultancy/advisory board fees from Roche, AstraZeneca, Tesaro, Clovis, Onxeo, MSD, GSK, and Genentech; research funding from PharmaMar; and travel expenses from Roche, AstraZeneca, and GSK. All remaining authors have declared no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Portable sensors have emerged as a promising solution for personal exposure (PE) measurement. For the first time in Île-de-France, PE to black carbon (BC), particulate matter (PM), and nitrogen dioxide (NO 2 ) was quantified based on three field campaigns involving 37 volunteers from the general public wearing the sensors all day long for a week. This successful deployment demonstrated its ability to quantify PE on a large scale, in various environments (from dense urban to suburban, indoor and outdoor) and in all seasons. The impact of the visited environments was investigated. The proximity to road traffic (for BC and NO 2 ), as well as cooking activities and tobacco smoke (for PM), made significant contributions to total exposure (up to 34%, 26%, and 44%, respectively), even though the time spent in these environments was short. Finally, even if ambient outdoor levels played a role in PE, the prominent impact of the different environments suggests that traditional ambient monitoring stations is not a proper surrogate for PE quantification.

Introduction: Overseas France represents 18 % of French territory and is home to 4 % of its population for whom there is unequal treatment in the field of rare/complex cancer., Aim: To report our experience of intercontinental multidisciplinary videoconferencing between the French mainland and Pacific territories., Methods: Every other friday, three centers located in Papeete, Nouméa and Paris-Villejuif connected between 6:30 AM and 8:00 AM GMT to discuss cases of rare/complex cancers., Results: Between November 2019 and December 2020, 323 presentations implicating 233 patients involved sarcoma (n=93), digestive pathology (n=60), neuroendocrine tumors (n=35), urology (n=24), gynecology (n=24), neurology (n=16), thyroid pathology (n=14), dermatology (n=14), senology (n=11), hematology (n=11), ENT pathology (n=10), pathology thoracic (n=10) and pediatrics (n=1). Of the 233 patients, 134 (57.5 %) living in New Caledonia and 99 (42.5 %) in French Polynesia, 117 (50.5 %) had metastatic disease. 39 patients (16.7 %) were transferred to French mainland (EVASAN), for surgery (n=25), vectorized radiotherapy (n=7), biopsy (n=5), chemotherapy (n=1) or inclusion in a clinical trial (n=1). 195 patients (83.7 %) were treated at home, 15 (6.4 %) are still awaiting a decision and 4 (1.7 %) lost to follow-up., Conclusion: The use of videoconferencing to discuss rare/complex cancer cases was effective in guaranteeing French overseas population access to innovative therapies and clinical trials, limiting the need for intercontinental transfer to 16.7 %., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Objective: Mice lacking the bHLH transcription factor (TF) Neurog3 do not form pancreatic islet cells, including insulin-secreting beta cells, the absence of which leads to diabetes. In humans, homozygous mutations of NEUROG3 manifest with neonatal or childhood diabetes. Despite this critical role in islet cell development, the precise function of and downstream genetic programs regulated directly by NEUROG3 remain elusive. Therefore, we mapped genome-wide NEUROG3 occupancy in human induced pluripotent stem cell (hiPSC)-derived endocrine progenitors and determined NEUROG3 dependency of associated genes to uncover direct targets., Methods: We generated a novel hiPSC line (NEUROG3-HA-P2A-Venus) where NEUROG3 is HA-tagged and fused to a self-cleaving fluorescent VENUS reporter. We used the CUT&RUN technique to map NEUROG3 occupancy and epigenetic marks in pancreatic endocrine progenitors (PEP) that were differentiated from this hiPSC line. We integrated NEUROG3 occupancy data with chromatin status and gene expression in PEPs as well as their NEUROG3-dependence. In addition, we investigated whether NEUROG3 binds type 2 diabetes mellitus (T2DM)-associated variants at the PEP stage., Results: CUT&RUN revealed a total of 863 NEUROG3 binding sites assigned to 1263 unique genes. NEUROG3 occupancy was found at promoters as well as at distant cis-regulatory elements that frequently overlapped within PEP active enhancers. De novo motif analyses defined a NEUROG3 consensus binding motif and suggested potential co-regulation of NEUROG3 target genes by FOXA or RFX transcription factors. We found that 22% of the genes downregulated in NEUROG3 -/- PEPs, and 10% of genes enriched in NEUROG3-Venus positive endocrine cells were bound by NEUROG3 and thus likely to be directly regulated. NEUROG3 binds to 138 transcription factor genes, some with important roles in islet cell development or function, such as NEUROD1, PAX4, NKX2-2, SOX4, MLXIPL, LMX1B, RFX3, and NEUROG3 itself, and many others with unknown islet function. Unexpectedly, we uncovered that NEUROG3 targets genes critical for insulin secretion in beta cells (e.g., GCK, ABCC8/KCNJ11, CACNA1A, CHGA, SCG2, SLC30A8, and PCSK1). Thus, analysis of NEUROG3 occupancy suggests that the transient expression of NEUROG3 not only promotes islet destiny in uncommitted pancreatic progenitors, but could also initiate endocrine programs essential for beta cell function. Lastly, we identified eight T2DM risk SNPs within NEUROG3-bound regions., Conclusion: Mapping NEUROG3 genome occupancy in PEPs uncovered unexpectedly broad, direct control of the endocrine genes, raising novel hypotheses on how this master regulator controls islet and beta cell differentiation., (Copyright © 2021 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: The optimal surgical procedure for duodenal gastrointestinal stromal tumors (D-GISTs) remains poorly defined. Pancreaticoduodenectomy (PD) allows for a wide resection but is associated with a high morbidity rate., Objectives: The aim of this study was to compare the short- and long-term outcomes of PD versus limited resection (LR) for D-GISTs and to evaluate the role of tumor enucleation (EN)., Methods: In this retrospective European multicenter cohort study, 100 patients who underwent resection for D-GIST between 2001 and 2013 were compared between PD (n = 19) and LR (n = 81). LR included segmental duodenectomy (n = 47), wedge resection (n = 21), or EN (n = 13). The primary objective was to evaluate disease-free survival (DFS) between the groups, while the secondary objectives were to analyze the overall morbidity and mortality, radicality of resection, and 5-year overall survival (OS) and recurrence rates between groups. Furthermore, the short- and long-term outcomes of EN were evaluated., Results: Baseline characteristics were comparable between the PD and LR groups, except for a more frequent D2 tumor location in the PD group (68.3% vs. 29.6%; p = 0.016). Postoperative morbidity was higher after PD (68.4% vs. 23.5%; p < 0.001). OS (p = 0.70) and DFS (p = 0.64) were comparable after adjustment for D2 location and adjuvant therapy rate. EN was performed more in American Society of Anesthesiologists (ASA) stage III/IV patients with tumors < 5 cm and was associated with a 5-year OS rate of 84.6%, without any disease recurrences., Conclusions: For D-GISTs, LR should be the procedure of choice due to lower morbidity and similar oncological outcomes compared with PD. In selected patients, EN appears to be associated with equivalent short- and long-term outcomes. Based on these results, a surgical treatment algorithm is proposed., (© 2021. Society of Surgical Oncology.)

Background: The aim of the study is to evaluate functional and oncological outcomes of patients undergoing abdominal wall soft tissue tumors (AWSTT) surgery., Methods: All consecutive patients that underwent surgery for malignant and intermediate AWSTT from 1999 to 2019 were retrospectively analyzed., Results: Ninety-two patients were identified, 20 (22%) operated on for a desmoid tumor and 72 (78%) for a soft tissue sarcoma (STS). Fifty-two patients (57%) had in toto resection of the abdominal wall (from the skin to the peritoneum) and 9 (10%) required simultaneous visceral resection. The closure was direct in 28 patients (30%) and requiring a mesh, a flap or a combination of the two in respectively 42, 16, and 6 patients (47%, 17%, 6%). The postoperative complications rate was 26%. Thirteen patients (14%) developed an incisional hernia after a median delay of 27 months. After a median follow-up of 40 months, out of the 72 patients operated on for STS, 7 (10%) developed local recurrence and 11 (15%) distant recurrence. The median recurrence-free and overall survivals were 61 and 116, months respectively., Conclusions: Management of AWSTT requires extensive surgery but allows good local control with an acceptable rate of incisional hernia., (© 2021 Wiley Periodicals LLC.)

Radiation therapy is a standard treatment for limbs soft tissue sarcomas. Preoperative versus postoperative radiotherapy has been a controversial topic for years. With preoperative irradiation, the treatment volume is more limited, the delivered dose possibly lower and the tumor volume easier to delimit. Only one randomized trial compared these two irradiation sequences. The results in terms of local control and survival were equivalent but the risk of acute postoperative complications was higher if irradiation was administered before surgery. However, in the latest update of this trial, patients who received adjuvant irradiation exhibited more severe late toxicity than those treated preoperatively. In addition, with modern irradiation techniques such as conformal with image-guided intensity modulated radiotherapy and flap coverage techniques, the incidence of complications after preoperative irradiation were lower than historically published rates. Locally advanced proximal sarcomas and the failure of other neoadjuvant treatments are nowadays classical indications for preoperative irradiation. As with other neoadjuvant treatments, induction radiotherapy must be personalized according to the histological subtype, the tumor site and the benefit/risk ratio, which is best appreciated by a multidisciplinary surgical and oncological team in a specialized center in the management of soft-tissue sarcomas., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Purpose: To report our experience of intercontinental multidisciplinary oncology videoconferencing between the French mainland and South Pacific to discuss rare and/or complex cancer cases., Methods: On the first and third Friday of each month, all participants connected between 6:30 am and 8:00 am GMT to discuss using a web conference service., Results: Between November 2019 and April 2020, 99 cases concerning 78 patients were discussed. Oncology subspecialties required were sarcoma (n = 36), digestive (n = 29), dermatology (n = 5), gynecology (n = 5), breast (n = 5), urology (n = 5), hematology (n = 5), ENT (n = 3), thoracic (n = 3), thyroid (n = 2), and pediatric (n = 1). Median patient age was 58 years, 41 were female (53%), 37 were male (47%), and 43 had a metastatic disease (55%). Following discussion, 16 patients (21%) were transferred to the French mainland. Reasons for transfer were requirement for complex surgery (n = 11) and need for specialized diagnostic biopsy (n = 5). Fifty-six patients were treated locally, with systemic chemotherapy (n = 36), surveillance (n = 8), surgery (n = 8), radiotherapy (n = 3), or endoscopy (n = 1). Direct benefits for patients treated in their local facility included strategy changes (surveillance or surgery contraindication, n = 9), targeted therapy decision (n = 14), immunotherapy decision (n = 9), and diagnostic or metastatic status corrections (n = 4). Six patients are still awaiting decision., Conclusion: Using real-time intercontinental multidisciplinary oncology videoconferencing to discuss complex or rare cancer cases is reliable and effective for decision making. This concept helped to limit to 21% the need for transfers to the mainland., Competing Interests: Olivier MirStock and Other Ownership Interests: Transgene, Amplitude Surgical, IpsenHonoraria: RocheConsulting or Advisory Role: Lilly, Pfizer, Roche, Lundbeck, JanssenSpeakers' Bureau: Lilly, Roche, PfizerResearch Funding: Ipsen, AstraZeneca, Blueprint MedicinesTravel, Accommodations, Expenses: Roche, Pfizer Arthur GeraudEmployment: As part of the Drug Development Department (DITEP)Research Funding: As part of the Drug Development Department (DITEP) Emeline ColombaHonoraria: IPSEN, Bristol Myers Squibb, PfizerConsulting or Advisory Role: Bristol Myers Squibb, GlaxoSmithKline, Novartis, Ipsen Michael MajerTravel, Accommodations, Expenses: Bristol Myers Squibb Corinne BalleyguierTravel, Accommodations, Expenses: General Electric Health Care, Siemens Healthineers, Bracco Diagnostics, Guerbet Benjamin BesseResearch Funding: AstraZeneca, Pfizer, Lilly, Onxeo, Bristol Myers Squibb, Inivata, AbbVie, Amgen, Blueprint Medicines, Celgene, GlaxoSmithKline, Ignyta, Ipsen, Merck KGaA, MSD Oncology, Nektar, PharmaMar, Sanofi, Spectrum Pharmaceuticals, Takeda, Tiziana Therapeutics, Cristal Therapeutics, Daiichi Sankyo, Janssen Oncology, OSE Immunotherapeutics, BeiGene, Boehringer Ingelheim, Roche/Genentech, Servier, Tolero Pharmaceuticals Michel DucreuxEmployment: SandozHonoraria: Servier, Lilly, Amgen, Roche/Genentech, Merck Serono, MSD Oncology, Ipsen, Bayer, Celgene, NovartisConsulting or Advisory Role: Roche, Merck Serono, Servier, Amgen, Novartis, Ipsen, Celgene, Lilly, Pierre Fabre, HalioDxSpeakers' Bureau: Roche, Merck KGaA, Celgene, Ipsen, BayerResearch Funding: Roche, KeocytTravel, Accommodations, Expenses: Ipsen, Roche, Merck Serono, Bayer, AmgenNo other potential conflicts of interest were reported.

Backgrounds: Multivisceral resection is the standard treatment for retroperitoneal sarcoma (RPS) during which pancreas resection may be necessary., Methods: All consecutive patients operated for RPS with pancreatectomy in 2 expert centers between 1993 and 2018 were retrospectively analyzed., Results: Fifty patients (median age: 57 years, IQR: [46-65]) with a primary (n = 33) or recurrent (n = 17) RPS underwent surgery requiring pancreas resection (distal pancreatectomy (DP) (n = 43), pancreaticoduodenectomy (PD) (n = 5), central pancreatectomy (n = 1), and atypical resection (n = 1)). Severe postoperative morbidity (Clavien-Dindo III-IV) was observed in 14 patients (28%), and 7 of them (14%) required reoperation for anastomotic bowel leakage (n = 5), gastric volvulus (n = 1), or hemorrhage (n = 1). Pancreas-related complications occurred in 25 patients (50%): 10 postoperative pancreatic fistulas (POPF) (grade A (n = 12), grade B (n = 6), grade C (n = 1)), 13 delayed gastric emptying (grade A (n = 8), grade B (n = 4), grade C (n = 1)), 1 hemorrhage (grade C). Postoperative mortality was 4% (n = 2), all following PD, caused by a massive intraoperative air embolism and by a multiple organ failure after anastomotic leakage. Pathological analysis confirmed pancreatic involvement in 17 (34%) specimens. Microscopically complete resection (R0) was achieved in 22 (44%) patients. After a follow-up of 60 months, 36 patients (75%) were still alive, among whom 27 without recurrence (56%)., Conclusion: Pancreatic resection during RPS surgery is associated with significant postoperative morbidity and mortality. PD should be avoided whenever possible while other procedures seemed achievable without excessive morbidity and with long-term survival., (© 2020. The Society for Surgery of the Alimentary Tract.)

Background: Changes in the management of patients with cancer and delays in treatment delivery during the COVID-19 pandemic may impact the use of hospital resources and cancer mortality., Patients and Methods: Patient flows, patient pathways and use of hospital resources during the pandemic were simulated using a discrete event simulation model and patient-level data from a large French comprehensive cancer centre's discharge database, considering two scenarios of delays: massive return of patients from November 2020 (early-return) or March 2021 (late-return). Expected additional cancer deaths at 5 years and mortality rate were estimated using individual hazard ratios based on literature., Results: The number of patients requiring hospital care during the simulation period was 13,000. In both scenarios, 6-8% of patients were estimated to present a delay of >2 months. The overall additional cancer deaths at 5 years were estimated at 88 in early-return and 145 in late-return scenario, with increased additional deaths estimated for sarcomas, gynaecological, liver, head and neck, breast cancer and acute leukaemia. This represents a relative additional cancer mortality rate at 5 years of 4.4 and 6.8% for patients expected in year 2020, 0.5 and 1.3% in 2021 and 0.5 and 0.5% in 2022 for each scenario, respectively., Conclusions: Pandemic-related diagnostic and treatment delays in patients with cancer are expected to impact patient survival. In the perspective of recurrent pandemics or alternative events requiring an intensive use of limited hospital resources, patients should be informed not to postpone care, and medical resources for patients with cancer should be sanctuarised., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: No author reported potential conflict of interest in link with the submitted work. A.B. reports personal fees from Roche SAS. I.B. reports personal fees from Roche, Novartis, CSL Behring and Takeda. M.F. reports fees from HRA Pharma (participation to board) and travel grants from Ipsen, Pfizer and Novartis. S.D. reports grants and non-financial support from Pfizer, grants from Novartis, grants and non-financial support from AstraZeneca, grants and non-financial support from Roche Genentech, grants from Lilly, grants from Puma, grants from Myriad, grants from Orion, grants from Amgen, grants from Sanofi, grants from Genomic Health, grants from GE, grants from Servier, grants from MSD, grants from BMS, grants from Pierre Fabre, grants from Seagen and grants from Exact Sciences. L.A. reports a consulting/advisory role for Novartis (Institution), Amgen (Institution), Bristol Myers Squibb (Institution), Ipsen (Institution), Roche (Institution), Pfizer (Institution), Astellas Pharma (Institution), Merck (Institution), MSD (Institution), AstraZeneca (Institution), Exelixis (Institution), Corvus Pharmaceuticals (Institution) and Peloton Therapeutics (Institution) and research Funding from Bristol Myers Squibb (Institution). D.P. reports a consulting, advisory role or lectures for AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche and Samsung; honoraria from AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche and Samsung; institutional financial interests (clinical trials research as the principal or co-investigator) from AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, MedImmune, Sanofi-Aventis, Taiho Pharma, Novocure and Daiichi Sankyo and travel and accommodation expenses from AstraZeneca, Roche, Novartis, prIME Oncology and Pfizer. M.D. reports honoraria for advisory boards or as a presenter in symposium from Merck Serono, MSD, AMGEN, Roche, Bayer, Ipsen, Pfizer, Servier, Pierre Fabre, HalioDx, Lilly and Sanofi. E.C. reports consulting advisory board activity for BMS, Ipsen, Sanofi, Pfizer, GSK and Merck. C.R. reports a consultant/advisory role for Bristol Myers Squibb, MSD, Roche, Novartis, Amgen, Sanofi and Pierre Fabre. C.M. reports consultant/advisory fees from Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi and Orion and as acted as a principal/sub-investigator of clinical trials for AbbVie, Aduro, Agios, Amgen, Argen-x, Astex, AstraZeneca, Aveo pharmaceuticals, Bayer, BeiGene, Blueprint, BMS, Boehringer Ingelheim, Celgene, Chugai, Clovis, Daiichi Sankyo, Debiopharm, Eisai, Eos, Exelixis, Forma, GamaMabs, Genentech, Gortec, GSK, H3 Biomedecine, Incyte, Innate Pharma, Janssen, Kura Oncology, Kyowa, Lilly, Loxo, Lysarc, Lytix Biopharma, MedImmune, Menarini, Merus, MSD, Nanobiotix, Nektar Therapeutics, Novartis, Octimet, Oncoethix, Oncopeptides AB, Orion, Pfizer, PharmaMar, Pierre Fabre, Roche, Sanofi, Servier, Sierra Oncology, Taiho, Takeda, Tesaro and Xencor. J.B.M. reports personal fees from AbbVie, Jazz PHARMA and Astellas. S.M. reports personal fees from statistical advice to IDDI, Janssen Cilag and Amaris and from data and safety monitoring membership of clinical trials (Hexal, Steba, IQVIA, Roche, Sensorion, Biophytis, Servier and Yuhan). A.A. reports grant support, paid to her institution, from F. Hoffmann-La Roche. F.B. reports personal financial interests with AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, Mirati, MSD, Pierre Fabre, Pfizer, Seattle Genetics and Takeda; institutional financial interests with AbbVie, ACEA, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eisai, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Genentech, Ipsen, Ignyta, Innate Pharma, Loxo, Novartis, MedImmune, Merck, MSD, Pierre Fabre, Pfizer, Sanofi-Aventis and Takeda and non-financial interests (as a principal investigator) for AstraZeneca, BMS, Merck, Pierre Fabre and F. Hoffmann-La Roche, Ltd–sponsored trials (or ISR). J.B. reports honoraria from Bristol Myers Squibb; a consulting or advisory role for Bristol Myers Squibb, MSD, PharmaMar (Inst), Bristol Myers Squibb (Inst) and Merck Serono (Inst) and travel and accommodation expenses from Bristol Myers Squibb. Other authors report no conflict of interest. Y. Takahashi declares no conflict of interest. Her editorial work for the present article has been funded by Inserm., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

(1) Background: locally resected high-grade sarcomas relapse in 40% of cases. There is no prognostic or predictive genomic marker for response to peri-operative chemotherapy. (2) Methods: MOSCATO and ProfiLER are pan-tumor prospective precision medicine trials for advanced tumors. Molecular analysis in both trials comprised targeted next-generation sequencing and comparative genomic hybridization array. We investigated if molecular alterations identified in these trials in sarcomas were associated with disease-free survival (DFS) and response to anthracyclines. (3) Results: this analysis included 215 sarcomas, amongst which 53 leiomyosarcomas, 27 rhabdomyosarcomas, 20 undifferentiated pleomorphic sarcomas, and 17 liposarcomas. The most frequently altered gene was TP53 (46 mutations and eight deletions). There were 149 surgically resected localized sarcomas. Median DFS in TP53 wild type (WT), deleted, and mutated sarcomas was 16, 10, and 10 months, respectively ( p = 0.028; deletions: HR = 1.55; 95% CI = 0.75-3.19; mutations: HR = 1.70; 95%CI = 1.13-2.64). In multivariate analysis, TP53 mutations remained associated with shorter DFS ( p = 0.027; HR = 2.30; 95%CI = 1.10-4.82). There were 161 localized and advanced sarcomas evaluable for response to anthracyclines. Objective response rates were 35% and 55% in TP53 WT and mutated sarcomas, respectively (OR = 2.24; 95%CI = 1.01-5.03; p = 0.05). In multivariate analysis, TP53 mutations remained associated with increased response (OR = 3.24; 95%CI = 1.30-8.45; p = 0.01). (4) Conclusions: TP53 mutations are associated with shorter DFS and increased response to anthracyclines. Post-validation, these findings could assist in decision-making for peri-operative treatments.

Aim: To prospectively assess toxicities of curative-intent intensity-modulated conformal radiotherapy (IMRT) in patients with extremity soft tissue sarcomas (ESTS)., Methods: Data from 59 consecutive patients with ESTS between 2014 and 2019 were both retrospectively and prospectively analysed. Toxicity data were collected both by confidential mailed survey (39% completed) and medical charts, and graded according to CTCAE v5.0. Normal tissues dosimetric data (healthy soft tissue segment, joint and bone) were included. The healthy soft tissue segment was created by adding 5 cm on either side of the PTV on CT axial slices, the PTV and bone (and articulation if present) were then removed from the generated volume., Results: IMRT was delivered post-operatively for nearly half of patients (n = 24, 41%), preoperatively for 18 (31%) and exclusively for 17 (28%; salvage: 13% or immediately inoperable: 15%). The median total dose delivered to the planned target volume (PTV) was 50.4 Gy (36-68 Gy) and 13 patients (22%) received a boost. With a median follow-up of 27 months (6-94 months), a total of 87 late effects were identified in 44/59 (75%) patients: 89% G1-2, and 11% G3-4. The main G1-2 toxicities were: functional limitation (36%), oedema (29%), gait disorders (20%), neurological disorders (20%) and chronic pain (32%). G3-4 toxicities were pain (n = 2), arterial stricture (n = 1) and a chronic wound requiring skin graft (n = 2). No bone fracture was observed. Quality of life was rated as good or very good in 70% patients who completed the survey. Larger (>3500 cm 3 ) healthy soft tissue segment volume was associated with decreased late toxicities (p = 0.02). No other predictive factor of toxicity was identified. The 2-year rates of local control, overall survival and recurrence-free survival were 90%, 90% and 64%, respectively., Conclusion: Healthy soft tissue segment volume influenced toxicity. Long-term prospective monitoring in a homogeneous population remains critical to assess the impact of IMRT induced chronic toxicity in ESTS patients. This should ideally lead to a validated normal tissue dose constraint (e.g.: healthy soft tissue segment volume > 3500 cm 3 ) to recommend for practitioners to help reduce the late toxicity risk., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

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.

Background and Objectives: During the worldwide pandemic of coronavirus disease 2019 (COVID-19), oncological procedures considered to be urgent could not be delayed, and a specific procedure was required to continue surgical activity. The objective was to assess the efficacy of our preoperative screening algorithm., Methods: This observational retrospective study was performed between the 25th of March and the 12th of May 2020 in a comprehensive cancer center in France. Patients undergoing elective oncologic surgery were tested by preoperative nasopharyngeal reverse-transcription polymerase chain reaction (RT-PCR) that could be associated with a chest computerized tomography (CT) scan., Results: Of the 510 screening tests (in 477 patients), only 5% (15/477) were positive for COVID-19 in 24 patients (18 RT-PCR+ and 7 CT scan+/RT-PCR-). Four patients were ultimately false positives based on the CT scan. In total, only 4.2% (20/477) of the patients were COVID-19+. The positivity rate decreased with time after the containment measures were implemented (from 7.4% to 0.8%). In the COVID-19+ group, 20% of the patients had postoperative pulmonary complications, whereas this was the case for 5% of the patients in the COVID-19 group., Conclusions: Maintaining secure surgical activity is achievable and paramount in oncology care, even during the COVID-19 pandemic, with appropriate screening based on preoperative RT-PCR., (© 2021 Wiley Periodicals LLC.)

Background: This study aimed to investigate changes in treatment strategy and outcome for patients with primary retroperitoneal sarcoma (RPS) undergoing resection at referral centers during a recent period., Methods: The study enrolled consecutive adult patients with primary non-metastatic RPS who underwent resection with curative intent between 2002 and 2017 at 10 referral centers. The patients were grouped into three periods according to date of surgery: t1 (2002-2006), t2 (2007-2011), and t3 (2012-2017). Five-year overall survival (OS), disease-specific survival (DSS), and crude cumulative incidence (CCI) of local recurrence (LR) and distant metastasis (DM) were calculated. Multivariable analyses for OS and DSS were performed., Results: The study included 1942 patients. The median follow-up period after resection varied from 130 months (interquartile range [IQR], 124-141 months) in t1 to 37 months (IQR, 35-39 months) in t3. The 5-year OS was 61.2% (95% confidence interval [CI], 56.4-66.3%) in t1, 67.0% (95 CI, 63.2-71.0%) in t2, and 71.9% (95% CI, 67.7-76.1%) in t3. The rate of macroscopically incomplete resection (R2) was 7.1% in t1 versus 4.7% in t3 (p = 0.066). The median number of resected organs increased over time (p < 0.001). In the multivariable analysis resection during t3 was associated with better OS and DSS. The 90-day postoperative mortality improved over time (4.3% in t1 to 2.3% in t3; p = 0.031). The 5-year CCI of LR and DM did not change significantly over time., Conclusions: The long-term survival of patients who underwent resection for primary RPS has increased during the past 15 years. This increased survival is attributable to better patient selection for resection, quality of surgery, and perioperative patient management.

Therapeutic options in patients with metastatic osteosarcoma are limited and effective systemic treatments are needed in this setting. The aim of this case series was to assess the efficacy and toxicity of oral metronomic etoposide in adult patients with progressive metastatic osteosarcoma. We retrospectively reviewed the electronic records of patients treated with oral metronomic etoposide (25 mg thrice daily, 3 weeks out of 4) from December 2002 to December 2018 at Gustave Roussy (Villejuif, France). The primary endpoint was progression-free rate (PFR) at 4 months; secondary endpoints were: best response (according to RECIST v1.1), progression-free survival (PFS), overall survival (OS) and safety. With a median follow-up of 9.8 months, 37 patients were eligible for this analysis: 68% males, median age 42 (range: 21-75), 19% with synchronous metastases, 92% with lung metastases, median PS: 1 (range: 0-3). Median number of previous treatment lines in the metastatic setting was 1 (range: 0-4). Progression-free rate at 4 months was 40.3% (95% CI: 24.5-56.2). Best response was partial response in 11% and stable disease in 35% of patients (disease control rate: 46%). Median PFS was 3.1 months (95% CI: 2.5-4.7) and median OS was 9.8 months (95% CI: 5.1-12.3). Toxicity profile was acceptable, with 13% grade 3 haematological toxicities (anaemia and neutropenia), without any grade 3-4 non-haematological toxicity. In our experience, oral metronomic etoposide demonstrated effective palliation along with acceptable toxicity in patients with progressive metastatic osteosarcoma., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Desmoid tumours (DTs) are rare tumours originating from musculoaponeurotic structures. Although benign, they may be locally aggressive, leading to pain and disability. European Society for Medical Oncology (ESMO) guidelines recommend frontline watchful waiting and medical treatment in progressing tumours. Cryoablation is an interventional radiology technique that is suitable for DT patients (pts) on the basis of repeated cycles of freezing, leading to cell death., Methods: CRYODESMO-01 (ClinicalTrials.gov Identifier: NCT02476305) is a prospective, open-label, non-randomised, non-comparative, multicenter study assessing cryoablation in non-abdominopelvic progressing DT. Inclusion criteria were: pts ≥18 y.o., confirmed DT accessible to cryoablation (≥90% destruction), measurable lesion conforming to modified response evaluation criteria in solid tumours (mRECIST), progressive disease after ≥2 lines of medical therapy or with functional symptoms/pain, adequate biological parameters, informed consent, and affiliation to a medical insurance scheme. The primary end-point was the non-progression rate at 12 months; secondary end-points included safety, quality of life (QoL), assessment of pain and functional status., Findings: 50 pts were enrolled (78% female) from four French centres and all were treated. The mean age was 41 y.o. (19-73). The median number of prior treatments was 2.00 [1-4] including non-steroidal anti-inflammatory drugs (NSAIDs), hormone therapy, chemotherapy, and anti-angiogenics. Tumour location included limbs (36%), trunk (60%), and cervical area (4%). The median tumour largest diameter was 89 mm. The rate of non-progressing disease at +12 months was 86% [confidence level (CI) 95% 73-94%]. Median PFS was not reached at a median follow-up of 31 months. Grade 1 and 2 toxicity occurred in 32.8% and 44.5% of patients, grade 3-4 in 22% and no Grade 5 toxicity was observed. Cryoablation significantly improved functional status and pain scores., Interpretation: Cryoablation demonstrated feasibility in progressive DT pts. The study met is primary end-point with 86% of non-progressive disease at +12 months, with reduced pain, better functional status, and encouraging long-term disease control., Competing Interests: Conflict of interest statement Dr Buy received consulting fees from Galil-BTG; Dr Deschamps received grants from Boston Scientific; Dr Garnon received consulting fees from Boston-Galil, Johnson & Johnson, Canon Medical, Medtronic; Pr Gangi received consulting fees from BTG and has a patent from Apriomed., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Peritoneal metastases from neuroendocrine tumors are associated with a bad prognosis. The objective of our study was to evaluate whether surgical resection could lead to prolonged survival in selected patients. This survival was compared to that of patients operated for liver metastasis., Methods: From our prospectively maintained database we included 88 patients who underwent the complete resection of peritoneal and/or liver metastasis between January 1995 and December 2016 in Gustave-Roussy. Three resection groups were compared: peritoneal metastasis alone, liver metastasis alone, and the combined resection of liver and peritoneal metastases., Results: The median peritoneal cancer index was 10 in the peritoneal group and 11 in the peritoneal + liver group. The 5-year overall survival was 81% (60-100) in the peritoneal group compared to 78% (65.2-92.8) in the liver group, and 72% (58.7-89.7) in the peritoneal + liver group (p = 0.71). The 3-year disease-free survival reached 26.9% (16.1-45.1) in the liver group, 12.5% (2.3-68.2) in the peritoneal group, and 32.4% (19.9-52.6) in the combined liver + peritoneal group (p = 0.45). In the univariate analysis, the prognosis factors for a longer survival were: small bowel primary tumor origin, low preoperative chromogranin A level, and tumor grade ≤1., Conclusion: Despite a high recurrence rate, long-term overall survival can be achieved after the resection of peritoneal metastasis in selected patients. This survival is comparable to that of patients operated for liver metastasis only. Surgery should stand as a standard treatment for peritoneal metastases in patients with resectable disease., (© 2020 S. Karger AG, Basel.)

Purpose: Desmoid-type fibromatosis (DF) are locally aggressive neoplasms, with a need for effective systemic treatment in case of progression to avoid the short- and long-term complications of local treatments., Experimental Design: We retrospectively analyzed the outcomes of adult patients with DF treated with oral vinorelbine (90 mg once weekly) at Gustave Roussy Cancer Institute (Villejuif, Paris, France). Only patients with documented progressive disease according to RECIST v1.1 for more than 3 months (±2 weeks) before treatment initiation were included., Results: From 2009 to 2019, 90 out of 438 patients with DF were eligible for this analysis. Vinorelbine was given alone in 56 patients (62%), or concomitantly with endocrine therapy in 34 patients, for a median duration of 6.7 months. A partial response was observed in 29% and stable disease in another 57%. With a median follow-up of 52.4 months, the median time to treatment failure (TTF) was not reached. Progression-free rates at 6 and 12 months were 88.7% and 77.5%, respectively. Concomitant endocrine therapy was associated with longer TTF in women [HR, 2.16; 95% confidence interval (CI), 1.06-4.37; P = 0.03). Among 64 patients with documented CTNNB1 mutational status, p.S45F or p.S45P mutations were associated with longer TTF compared with p.T41A or wild-type tumors (HR, 2.78; 95% CI, 1.23-6.27; P = 0.04). Toxicity profile was favorable, without grade 3-4 toxicity, except for one grade 3 neutropenia., Conclusions: Oral vinorelbine is an effective, affordable, and well-tolerated regimen in patients with advanced, progressive DF. Prolonged activity was observed in patients with tumors harboring CTNNB1 p.S45F or p.S45P mutations., (©2020 American Association for Cancer Research.)

Background: Imatinib is the standard first-line therapy in metastatic gastrointestinal stromal tumours (GIST). Investigational multi-kinase inhibitors (MKIs) such as nilotinib, dasatinib or masitinib have been tested as first-line therapies in phase II/III studies. This might theoretically result either in increased survival or in early emergence of resistance to approved MKIs., Methods: To assess whether using MKIs other than imatinib in first line decreases imatinib efficacy in second line for patients with GIST, a retrospective chart review was performed from 2005 to 2011 in two French tertiary centres of patients with GIST who received investigational MKIs (in phase II/III trials) as first-line treatment, followed by imatinib as second line., Results: Of 46 patients, (55% women, median age 55 years (range 24-81)), 22 (47%) had a KIT exon 11 mutation, 1 a KIT exon 9 mutation (2%), 1 a PDGFRA D842V mutation (2%). Out of 46 patients, 21 (46%) received masitinib, 17 (37%) received dasatinib and 8 (17%) received nilotinib as first-line treatment with a median progression-free survival of 18.0 months (95% CI: 8.5 to 25.5). Median time to imatinib failure was 19.7 months (95% CI: 13.5 to 29.0). Median time to second relapse was 48.7 months (95% CI: 31.2 to 72.0). Median overall survival from time of initial metastasis diagnosis was 5.7 years (95% CI: 4.5 to 7.4)., Conclusions: Patients with GIST who received investigational MKIs as first-line treatment and imatinib as second line had a time to second relapse longer than that observed historically with imatinib in first line, suggesting that using MKIs other than imatinib in first line does not decrease the efficacy of subsequent treatment lines., Competing Interests: Competing interests: JA has a consulting or advisory role for AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme and Roche; and research funding from Merck Sharp & Dohme (Inst) and Pierre Fabre (Inst). ER received honoraria from AstraZeneca (Inst), BMS (Inst) and Roche (Inst), has a consulting or advisory role for AstraZeneca, research funding from AstraZeneca (Inst) and accommodation expenses from AstraZeneca and BMS. MF received honoraria from Novartis (Inst) and accommodation expenses from Ipsen, Novartis and Pfizer. ALC received honoraria from Bayer, Lilly and PharmaMar. J-YB has leadership of Innate Pharma; received honoraria from AstraZeneca, BMS, MSD, PharmaMar and Roche; has a consulting or advisory role for Bayer, Blueprint, Deciphera, Pharmamar and Roche; received research funding from Bayer (Inst), GlaxoSmithKline (Inst), Novartis (Inst), Pharmamar (Inst) and Roche (Inst); and received accommodation expenses from Roche. OM has stock and other ownership interests in Amplitude Surgical, Ipsen and Transgene; honoraria from Roche; a consulting or advisory role for Janssen, Lilly, Lundbeck, Pfizer and Roche; is in the speakers’ bureau of Lilly, Pfizer and Roche; and received accommodation expenses from Pfizer and Roche. Other authors have no conflicts of interest to declare., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

Background: Unlike for extremity sarcomas, the efficacy of radiotherapy for retroperitoneal sarcoma is not established. The aim of this study was to evaluate the impact of preoperative radiotherapy plus surgery versus surgery alone on abdominal recurrence-free survival., Methods: EORTC-62092 is an open-label, randomised, phase 3 study done in 31 research institutions, hospitals, and cancer centres in 13 countries in Europe and North America. Adults (aged ≥18 years) with histologically documented, localised, primary retroperitoneal sarcoma that was operable and suitable for radiotherapy, who had not been previously treated and had a WHO performance status and American Society of Anesthesiologists score of 2 or lower, were centrally randomly assigned (1:1), using an interactive web response system and a minimisation algorithm, to receive either surgery alone or preoperative radiotherapy followed by surgery. Randomisation was stratified by hospital and performance status. Radiotherapy was delivered as 50·4 Gy (in 28 daily fractions of 1·8 Gy) in either 3D conformal radiotherapy or intensity modulated radiotherapy, and the objective of surgery was a macroscopically complete resection of the tumour mass with en-bloc organ resection as necessary. The primary endpoint was abdominal recurrence-free survival, as assessed by the investigator, and was analysed in the intention-to-treat population. Safety was analysed in all patients who started their allocated treatment. This trial is registered with ClinicalTrials.gov, NCT01344018., Findings: Between Jan 18, 2012 and April 10, 2017, 266 patients were enrolled, of whom 133 were randomly assigned to each group. The median follow-up was 43·1 months (IQR 28·8-59·2). 128 (96%) patients from the surgery alone group had surgery, and 119 (89%) patients in the radiotherapy and surgery group had both radiotherapy and surgery. Median abdominal recurrence-free survival was 4·5 years (95% CI 3·9 to not estimable) in the radiotherapy plus surgery group and 5·0 years (3·4 to not estimable) in the surgery only group (hazard ratio 1·01, 95% CI 0·71-1·44; log rank p=0·95). The most common grade 3-4 adverse events were lymphopenia (98 [77%] of 127 patients in the radiotherapy plus surgery group vs one [1%] of 128 patients in the surgery alone group), anaemia (15 [12%] vs ten [8%]), and hypoalbuminaemia (15 [12%] vs five [4%]). Serious adverse events were reported in 30 (24%) of 127 patients in the radiotherapy plus surgery group, and in 13 (10%) of 128 patients in the surgery alone group. One (1%) of 127 patients in the radiotherapy plus surgery group died due to treatment-related serious adverse events (gastropleural fistula), and no patients in the surgery alone group died due to treatment-related serious adverse events., Interpretation: Preoperative radiotherapy should not be considered as standard of care treatment for retroperitoneal sarcoma., Funding: European Organisation for Research and Treatment of Cancer, and European Clinical Trials in Rare Sarcomas., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Rectal gastrointestinal stromal tumours (GISTs) are rare tumours. Variability in the management may influence outcome, but there is a lack of understanding regarding contemporary variance in care. A multicenter, international, retrospective cohort study was performed to elucidate characteristics and outcomes of rectal GIST in European practice, with particular reference to surgical approach., Methods: All rectal GIST patients diagnosed between 2009 and 2018 were identified from five European databases. Recurrence free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier method. Possible confounders were identified using Cox regression analyses., Results: From 210 patients, 155 patients had surgery. The three main types of surgery were local tumour resection (LTR, n = 46), low anterior resection (LAR, n = 31) and abdomino-perineal resection (APR, n = 32). Most patients received neoadjuvant (65%) and/or adjuvant imatinib therapy (66%). Local recurrence rate after surgery was 15% and overall recurrence rate 28%. No significant differences were found in terms of RFS nor OS between LTR, LAR and APR. However, locally resected tumours were smaller, while LAR and APR patients more often received perioperative imatinib. General hospitals treated smaller GISTs, offered imatinib less frequently, and had a higher tumour rupture rate. In the multivariate analysis in the group having LTR, APR or LAR, the only significant prognostic factor for local recurrence was higher age (HR 1.06, CI 1.00-1.12, p = 0.048)., Conclusions: In European clinical practice for rectal GIST, LTR, LAR and APR have comparable local control. Multimodal approach is higher and tumour rupture less frequent in specialist centres compared to general hospitals., Competing Interests: Declaration of competing interest P. Rutkowski has received honoraria for lectures and Advisory Board from Novartis, Pfizer and Blueprint Medicines. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objectives: Literature assessing the effects of policies aimed at reducing traffic-related air pollution is scarce. The aims of this study were to evaluate the expected impacts, in terms of air quality and health effects, of various hypothetical low-emission zone (LEZ) scenarios in Greater Paris for a planned intervention in 2018/2019 which combine two different perimeters and two levels of vehicles ban, and to assess those impacts according to the socioeconomic status (SES) of the population., Methods: We evaluated the effects of four hypothetical LEZ scenarios on various stages of the full-chain model, more specifically, road traffic modelling (traffic flow, type of vehicles and related number of kilometers driven), emissions, fine scale PM 2.5 and NO 2 concentrations, related resident population exposure, and health effects. We computed the overall benefits of expected air pollution improvements in terms of preventable deaths and a decrease in new cases of the following three major chronic diseases: ischemic heart diseases in adults, asthma in children and low weight in full-term newborns., Results: The most stringent LEZ scenario would lower the maximum level of exposure from 55 μg/m 3 to 42 μg/m 3 in Paris. In one year, this scenario would help prevent: 340 deaths (-0.6%) representing 114,300 life years gained, 170 low-weight full-term births (-4.9%), 130 new cases of ischemic heart disease (IHD) (-1.8%) and 2930 new cases of asthma (-3.0%) among 9.4 million residents. Residents outside the LEZ would also benefit from this scenario. Results indicated that the intervention could contribute to increasing inequalities. The comparison of scenarios underlined the value of extending the LEZ to include a wider zone (including 80 more municipalities surrounding Paris). This would lead to a more equitable spread of the benefits over the population., Conclusion: Traffic control policies such as LEZ are difficult to accept for some categories of commuters and economic stakeholders. As of June 2019, the concertation process for the proposed Paris LEZ is still ongoing. This work provides authorities with detailed analyses of the options for this measure as well as information on related implications. It will help decision makers prioritize which preventive measures to introduce., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The optimal threshold of surgical margins for breast malignant phyllodes tumors (MPTs) and the impact of adjuvant chemotherapy and radiotherapy were investigated., Patients and Methods: We conducted a multicenter nationwide retrospective study of all MPT cases with central pathological review within the French Sarcoma Group. Endpoints were local recurrence-free survival (LRFS), metastasis-free survival (MFS), and overall survival (OS) rates., Results: Overall, 212 patients were included in the study. All non-metastatic patients underwent primary surgical treatment, including 58.6% of conservative surgeries. An R0 resection was achieved in 117 patients (59.4%: 26.9% of patients with 1-2 mm margins, 12.2% of patients with 3-7 mm margins, 20.3% of patients with ≥ 8 mm margins). Ninety-four patients (45%) underwent a second surgery (SS) to obtain R0 margins, with a final mastectomy rate of 72.6%. Radiotherapy and chemotherapy were performed in 91 (43.1%) and 23 patients (10.9%), respectively, but were not associated with better outcomes. Mastectomy was significantly associated with better LRFS (p < 0.001). Margins of 0, 1, or 2 mm with SS were associated with better MFS (hazard ratio [HR] 0.3, p = 0.005) and OS (HR 0.32, p = 0.005) compared with margins of 0-1-2 mm without SS. Wider margins (> 8 mm) were not superior to margins of 3-7 mm (3-7 mm vs. > 8 mm; HR 0.81, p = 0.69). Age (HR 2.14, p = 0.038) and tumor necrosis (HR 1.96, p = 0.047) were found to be poor prognostic factors and were associated with MFS., Conclusions: This study suggests that 3 mm margins are necessary and sufficient for surgical management of MPTs, and emphasizes the importance of SS to obtain clear margins in case of 0-1-2 mm margins. No impact of adjuvant chemotherapy or radiotherapy was detected in this study.

Background: Metastatic phyllodes tumors have poor prognosis with median overall survival of 11.5 months. The objective of this study is to identify prognostic factors and the best options for management of metastatic malignant phyllode tumors (MMPTs)., Patients and Methods: A multicentric retrospective study, including cases of MMPT from 10 sarcoma centers, was conducted. The primary end-point was overall survival (OS), and the secondary end-point was the clinical benefit of chemotherapy (CBCT) rate., Results: 51 MMPT patients were included. Median time from diagnosis to metastatic recurrence was 13 months. Management of MMPT consisted in surgery of the metastatic disease for 16 patients (31.3%), radiation therapy of the metastatic disease for 15 patients (31.9%), and chemotherapy for 37 patients (72.5%). Median follow-up was 62.1 months [95% confidence interval (CI) 31-80 months]. Median OS was 11.5 months (95% CI 7.5-18.7 months). On multivariate analysis, two or more metastatic sites [hazard ratio (HR) 2.81, 95% CI 1.27-6.19; p = 0.01] and surgery of metastasis (HR 0.33, 95% CI 0.14-0.78; p = 0.01) were independently associated with OS. The CBCT rate was 31.4% and 16.7% for the first and second lines. Polychemotherapy was not superior to single-agent therapy. Alkylating-agent-based chemotherapy, possibly associated with anthracyclines, was associated with a better CBCT rate than anthracyclines alone (p = 0.049)., Conclusions: The results of this study emphasize the impact of the number of metastatic sites on survival of MMPT patients and the leading role of metastasis surgery in MMPT management. If systemic therapy is used, it should include alkylating agents, which are associated with a better clinical benefit.