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Purpose The aim of this study was to create and validate dynamic nomograms to predict overall survival (OS) and disease-free survival (DFS) at different time points during follow-up in patients who had undergone resection of primary retroperitoneal sarcoma (RPS). Methods Patients with primary RPS operated upon between 2002 and 2017 at four and six referral centres comprised the development and external validation cohorts, respectively. Landmark analysis and multivariable Cox models were used to develop dynamic nomograms. Variables were selected using two backward procedures based on the Akaike information criterion. The prediction window was fixed at 5 years. Nomogram performances were tested in terms of calibration and discrimination on the development and validation cohorts. Results Development and validation cohorts totalled 1357 and 487 patients (OS analysis), and 1309 and 452 patients (DFS analysis), respectively. The final OS model included age, landmark time (TLM), tumour grade, completeness of resection and occurrence of local/distant recurrence. The final DFS model included TLM, histologic subtype, tumour size, tumour grade, multifocality and the interaction terms between TLM and size, grade and multifocality. For OS, Harrell C indices were higher than 0.7 in both cohorts, indicating very good discriminative capability. For DFS, Harrell C indices were between 0.64 and 0.72 in the development cohort and 0.62 and 0.68 in the validation cohort. Calibration plots showed good agreement between predicted and observed outcomes. Conclusion Validated nomograms are available to predict the 5-year OS and DFS probability at different time points throughout the first 5 years of follow-up in RPS survivors.

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.

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.

Highlights • Toxicity assessment in ESTS patients who received IMRT in real-life practice. • Prospective evaluation by confidential mailed survey. • Healthy soft tissue segment volume (median: 3911 cm3) associated with decreased toxicities. • This should be confirmed as a possible dosimetric constraint., 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 cm3) 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 cm3) to recommend for practitioners to help reduce the late toxicity risk.

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.

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.

(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.

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). 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. 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). 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.

Guidelines recommend that retroperitoneal sarcoma (RPS) be managed in a reference sarcoma center (RSC), but the benefit remains to be demonstrated. This study investigated the impact of initial surgery performed within the NetSarc network on overall survival (OS). NetSarc is a network of 26 RSCs with specialized multidisciplinary tumor boards (MDTs) that is funded by the French NCI. Since 2010, presentation to an MDT and second pathological review are mandatory for sarcoma patients, and data have been collected in a nationwide database. We extracted data for all patients who received surgery in or outside the network and who presented at a NetSarc center (NSC) for primary nonmetastatic RPS between 2010 and 2017. A total of 2945 patients were included: 1078 (36.6%) underwent the first surgery in an NSC, and 1867 (63.4%) in an out-of-network center. The median number of operations at an NSC during the study period was 23 (range: 3–209), and the corresponding median was 1 (range: 1–2) at out-of-network centers. The diagnostic procedures followed significantly more clinical practice guidelines within NetSarc, where there were significantly more first R0 resections [452 (41.9%) vs. 230 (12.3%)]. The OS was significantly superior for patients treated within NetSarc, with a 2-year OS of 87% vs. 70% (p

Background Soft-tissue sarcomas (STSs) are a group of rare cancers that can occur at any age. Prognostic outcomes of patients with STS are usually established at the time of the patient's initial disease presentation. Conditional survival affords a dynamic prediction of prognosis for patients surviving a given period after diagnosis. Estimates of conditional survival can provide crucial prognostic information for patients and caregivers, guide subsequent cancer follow-up schedules, and impact decisions regarding management. This study aims to estimate conditional survival and prognostic factors in patients with STS according to age at diagnosis (≤75 years and ≥75 years). Subjects, materials, and methods A total of 6,043 patients with nonmetastatic STS at first diagnosis who underwent complete surgical resection (R0 or R1) were assessed. Cox proportional hazards regression was used to establish prognostic factors of conditional metastasis-free survival and overall survival at 1, 2, and 5 years after diagnosis. Results Elderly patients have more adverse prognostic features at presentation and tend to receive less aggressive treatment than do younger patients. However, at baseline as well as at each conditional survival time point, the 5-year estimated probability of metastatic relapse decreases in both young and elderly patients and is almost identical in both groups at 2 years and 5 years after initial diagnosis. Prognostic factors for metastatic relapse and death change as patient survival time increases in both young and elderly patients. Grade, the strongest prognostic factor for metastatic relapse and death at baseline, is no longer predictive of metastatic relapse in patients surviving 5 years after initial diagnosis. Leiomyosarcoma is the histological subtype associated with the highest risk of metastatic relapse and death in young patients surviving 5 years after initial diagnosis. The positive impact on the outcome of peri-operative treatments tends to decrease and disappears in patients surviving 5 years after initial diagnosis. Conclusion Conditional survival estimates show clinically relevant variations according to time since first diagnosis in both young and elderly patients with STS. These results can help STS survivors adjust their view of the future and STS care providers plan patient follow-up. Implications for practice For patients with sarcoma who are followed up years after being treated for their disease, a common scenario is for the patient and caregivers to ask practitioners what the longer-term prognosis may be. The question posed to practitioners may be, "Doc, am I now cured? It's been 5 years since we finished treatment." Survival probability changes for patients who survive a given period of time after diagnosis, and their prognosis is more accurately described using conditional survival. By analyzing more than 6,000 sarcoma patients, an overall improvement was found in the risk of relapse as patients conditionally survive. Prognostic factors for metastatic relapse and death change as patient survival time increases in both young and elderly patients.

Background The current study investigated the role of radiotherapy (RT) in patients with primary nonmetastatic retroperitoneal liposarcomas. Methods A total of 607 patients with localized retroperitoneal well‐differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas (DDLPS) underwent surgical resection with or without RT at 8 high‐volume sarcoma centers (234 patients with WDLPS, 242 patients with grade 1 to 2 DDLPS, and 131 patients with grade 3 DDLPS; grading was performed according to the National Federation of Centers for the Fight Against Cancer [Federation Nationale des Centres de Lutte Contre le Cancer; FNCLCC]). RT was administered in 19.7%, 34.7%, and 35.1%, respectively, of these 3 cohorts. Overall survival (OS) was estimated using the Kaplan‐Meier method, and the incidences of local recurrence and distant metastasis (DM) were estimated in a competing risk framework. To account for bias consistent with nonrandom RT assignment, propensity scores were estimated. Cox univariable analysis of the association between RT and oncological endpoints was performed by applying inverse probability of treatment weighting (IPTW) using propensity scores. Results Age, tumor size, and the administration of chemotherapy were found to be significantly imbalanced between patients who did and did not undergo RT in all cohorts. IPTW largely removed imbalances in key prognostic variables. Although the 8‐year local recurrence incidences in patients treated with surgery plus RT versus surgery only were 11.8% and 39.2%, respectively, for patients with WDLPS (P = .011;); 29.0% and 56.7%, respectively, for patients with grade 1 to 2 DDLPS (P = .008); and 29.8% and 43.7%, respectively, for patients with grade 3 DDLPS (P = .025), this significant benefit was lost after IPTW analyses. There were no significant differences noted with regard to DM and OS between irradiated and unirradiated patients across all 3 cohorts. Conclusions Perioperative RT was found to be associated with better local control in univariable unadjusted analysis in all 3 cohorts, but not after accounting for imbalances in prognostic variables. RT did not impact on DM or OS. The appropriate selection of RT in this disease remains challenging. The results of the European Organization for Research and Treatment of Cancer (EORTC)–Soft Tissue and Bone Sarcoma Group (STBSG) 62092‐22092 prospective randomized trial are awaited., In the current study, the addition of radiotherapy to curative surgery is analyzed in a large, retrospective, multi‐institutional series of patients with primary retroperitoneal liposarcoma. Although there appears to be an association with better local control and outcome, this benefit is lost after propensity score adjustment. The authors currently are awaiting the results of the European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group 62092‐22092 prospective randomized trial examining the value of preoperative radiotherapy.

BackgroundSpatial 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.MethodsUsing 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.ResultsSome 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.ConclusionsIn 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 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.

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.

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.

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., Oral metronomic etoposide demonstrated effective palliation (progression‐free rate at 4 months was 40.3% (95%CI: 24.5‐56.2), along with acceptable toxicity in adult patients with metastatic osteosarcoma.

Multivisceral resection is the standard treatment for retroperitoneal sarcoma (RPS) during which pancreas resection may be necessary. All consecutive patients operated for RPS with pancreatectomy in 2 expert centers between 1993 and 2018 were retrospectively analyzed. 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%). 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.

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.

The Covid-19 pandemic is profoundly changing the organization of healthcare access. This is particularly so for peritoneal neoplastic diseases, for which curative treatment mobilizes substantial personnel, operating room and intensive care resources. The BIG-RENAPE and RENAPE groups have made tentative proposals for prioritizing care provision. A tightening of the usual selection criteria is needed for curative care: young patients with few or no comorbidities and limited peritoneal extension. It is desirable to prioritize disease conditions for which cytoreduction surgery with or without associated hyperthermic intraoperative peritoneal chemotherapy (HIPEC) is the gold-standard treatment, and for which systemic chemotherapy cannot be a temporary or long-term alternative: pseudomyxoma peritonei, resectable malignant peritoneal mesotheliomas, peritoneal metastases of colorectal origin if they are resectable and unresponsive to systemic chemotherapy after up to 12 courses, first-line ovarian carcinomatosis if resectable or in interval surgery after at most six courses of systemic chemotherapy. Addition of HIPEC must be discussed case by case in an expert center. The prioritization of indications must consider local conditions and the phase of the epidemic to allow optimal peri-operative care.

The optimal threshold of surgical margins for breast malignant phyllodes tumors (MPTs) and the impact of adjuvant chemotherapy and radiotherapy were investigated.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.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.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.

Introduction: This study evaluates the management of patients aged 0 to 30 years treated for sarcoma with data registered in the NETSARC French national database and compared the survival of adolescents and young adults (AYA) patients managed in reference sarcoma national centers (AYA in NC) and in non-NC (AYA outside NC). Patients and Methods: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers funded by the French National Cancer Institute. Patients’ characteristics and follow-up are prospectively collected in a database regularly monitored and updated. Patients’ survival was compared between groups. The primary endpoint was overall survival (OS). Secondary endpoints were local progression-free survival (LPFS), progression-free survival (PFS), and the quality of initial surgery. Results: Among 3,972 patients aged 0 to 30 years diagnosed between 2010 and 2017, 714 children, 1,290 AYAs in NC and 937 AYAs outside NC were included. Compliance to guidelines between AYAs treated in versus outside reference centers was significantly different (p

Desmoplastic Small Round Cell Tumor (DSRCT) is a rare abdominal disease of unknown origin affecting predominantly Caucasian children and young adult males characterized by a specific translocation t(11:22)(p13;q12), which fuses the ESWR1 gene to the WT1 gene. The estimated incidence ranges between 0.2 and 0.7 cases per million per year. DSRCT has an extremely aggressive clinical course, most patients having distant metastases at diagnosis, either peritoneal or extra-peritoneal. Despite a multimodal complex treatment, recurrence or progression is common and overall survival is poor.

Background Despite surgery, many patients experience locoregional recurrence (LR), the optimum treatment of which is still debated. Methods All 297 consecutive patients operated for a nonmetastatic primary retroperitoneal soft tissue sarcoma (RPS) between 1994 and 2017 were retrospectively analyzed to report our experience in treating LR. Results After a median follow-up of 97 months, 55 patients (19%) developed LR. The first site of recurrence was locoregional in 100% with associated peritoneal metastases in 45% and distant metastases in 5%. After LR treatment, the 1-, 3-, and 5-year overall survival (OS) rates were 71%, 46%, and 33%. Low tumor grade, disease-free interval above 24 months, exclusive LR, and well-differentiated liposarcoma were predictive of better OS. The treatment strategy (best supportive care, chemotherapy radiotherapy, and/or surgery) was not statistically significant. Fourteen patients underwent initial surveillance (strategic delay) for low-grade LR and eventually required treatment in 86% after a median delay of 20 months during which no patient developed distant metastases. Conclusions The management of LR in RPS is complex. An initial surveillance may not alter survival in asymptomatic low-grade and slow-growing LR. An LR decision scheme is proposed.

Peritoneal metastases are the third most common site of recurrence of colorectal cancer. Diagnosis is difficult and often made at an advanced stage even on imaging. Curative treatment relies on complete cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC), which dramatically improves survival in selected patients. Main prognostic factors are based on the extent of the peritoneal disease and the completeness of surgery. Therefore, identifying patients at high risk of developing peritoneal metastases with the aim of diagnosing and treating patients at an early stage appears crucial. Proactive attitude and prophylactic treatment based on HIPEC are being evaluated on clinical trials.

This report aims to describe preliminary results concerning secondary resectability after bidirectional chemotherapy for initially unresectable malignant peritoneal mesothelioma (MPM). Between January 2013 and January 2016, 20 consecutive patients treated for diffuse MPM not suitable for upfront surgery received bidirectional chemotherapy associating intraperitoneal and systemic chemotherapy. Evaluation of the response to chemotherapy was assessed clinically and by laparoscopy. The median peritoneal cancer index (PCI) score at staging laparoscopy was 27 (range 15–39). Altogether, 118 intraperitoneal chemotherapy cycles were administered without any specific adverse catheter-related event. Concerning tolerance, 85% of the patients experienced no pain or mild pain during chemotherapy administration. The clinical response rate was 60% after a median of three chemotherapy cycles. At laparoscopic reevaluation, the median PCI was 18 (range 0–35), and a secondary resectability was considered for 55% of the patients. Complete cytoreduction surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) was finally achieved for 10 patients (50%), with a median intraoperative PCI score of 14 (range 6–30). After a median follow-up period of 18 months, the 2-year overall survival rate was 83.3% for the patients treated by CRS followed by HIPEC and 44% for the patients treated by bidirectional chemotherapy. Bidirectional chemotherapy is a promising, well-tolerated treatment capable of increasing the resection rate for selected patients with diffuse MPM initially considered as unresectable or borderline resectable. For patients with definitively unresectable disease, bidirectional chemotherapy achieves a higher clinical response rate.

Background Well-designed observational studies of individuals with rare tumors are needed to improve patient care, clinical investigations, and the education of healthcare professionals. Methods The patterns of care, outcomes, and prognostic factors of a cohort of 2225 patients with metastatic soft tissue sarcomas who were diagnosed between 1990 and 2013 and documented in the prospectively maintained database of the French Sarcoma Group were analyzed. Results The median number of systemic treatments was 3 (range, 1–6); 27% of the patients did not receive any systemic treatment and 1054 (49%) patients underwent locoregional treatment of the metastasis. Half of the patients who underwent chemotherapy (n = 810) received an off-label drug. Leiomyosarcoma was associated with a significantly better outcome than the other histological subtypes. With the exception of leiomyosarcomas, the benefit of a greater than third-line regimen was very limited, with a median time to next treatment (TNT) and overall survival (OS) ranging between 2.3 and 3.7 months and 5.4 and 8.5 months, respectively. The TNT was highly correlated with OS. Female sex, leiomyosarcoma histology, locoregional treatment of metastases, inclusion in a clinical trial, and treatment with first-line polychemotherapy were significantly associated with improved OS in the multivariate analysis. Conclusions The combination of doxorubicin with a second drug, such as ifosfamide, represents a valid option, particularly when tumor shrinkage is expected to provide clinical benefits. After failure of the second-line therapy, best supportive care should be considered, particularly in patients with non-leiomyosarcoma histology who are not eligible to participate in a clinical trial. Locoregional treatment of metastasis should always be included in the therapeutic strategy when feasible. TNT may represent a useful surrogate endpoint for OS in clinical studies.

Background Despite a radical surgical approach to primary retroperitoneal sarcoma (RPS), many patients experience locoregional and/or distant recurrence. The objective of this study was to analyze post-relapse outcomes for patients with RPS who had initially undergone surgical resection of their primary tumor at a specialist center. Methods All consecutive patients who underwent macroscopically complete resection for primary RPS at 8 high volume centers from January 2002 to December 2011 were identified, and those who developed local recurrence (LR) only, distant metastasis (DM) only, or synchronous local recurrence and distant metastasis (LR+DM) during the follow-up period were included. Overall survival (OS) was calculated for all groups, as was the crude cumulative incidence of a second recurrence after the first LR. Multivariate analyses for OS were performed. Results In an initial series of 1007 patients with primary RPS, 408 patients developed recurrent disease during the follow-up period. The median follow-up from the time of recurrence was 41 months. The median OS was 33 months after LR (n = 219), 25 months after DM (n = 146), and 12 months after LR+DM (n = 43), and the 5-year OS rates were 29%, 20%, and 14%, respectively. Predictors of OS after LR were the time interval to LR and resection of LR, while histologic grade approached significance. For DM, significant predictors of OS were the time interval to DM and histologic subtype. The subgroup of patients who underwent resection of recurrent disease had a longer median OS than patients who did not undergo resection. Conclusions Relapse of RPS portends high disease-specific mortality. Patients with locally recurrent or metastatic disease should be considered for resection. Cancer 2017;123:1971-1978. © 2017 American Cancer Society.

Complete cytoreductive surgery (CCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have dramatically changed the prognosis of patients with pseudomyxoma peritonei (PMP). However, recurrences can still occur and no consensus has been reached regarding their optimal treatments. This study aimed to analyze the patterns of recurrence after CCRS plus HIPEC for PMP and potential subsequent treatments of these lesions.Between 1992 and 2014, patients who had relapsed after treatment of PMP were selected from a prospective database of 251 patients who had undergone CCRS plus HIPEC with a curative intent.After a median follow-up of 85 months, 66 patients (26%) had relapsed with a median free interval of 25 months. The first recurrence was mostly located in the peritoneum, isolated in 50 patients (76%) and associated with extraperitoneal disease in 6 patients. Curatively intended treatment of the relapse, combining surgery and chemotherapy was achievable in 76% of the patients, leading to a 5-year overall survival (OS) rate of 83% from the date of treatment of the first recurrence. In contrast, the 5-year OS rate was only 27% (p 0.001) for patients treated with non-curative therapy. An isolated peritoneal recurrence was predictive of greater amenability to curative therapy and a better prognosis.After CCRS plus HIPEC, serosal recurrences were more common than their distant counterparts. Distant relapses' emergence has raised the question of their optimal treatments. Very long-term survival can be obtained after further treatment of recurrent PMP for patients with limited disease and good general status.

Despite being associated with a very poor prognosis, long-term survivors across all series of Desmoplastic Small Round Cell Tumor (DSRCT) have been reported.To analyze patients 'characteristics associated with a prolonged survival after DSRCT diagnosis.All consecutive patients treated for DSRCT in nine French expert centers between 1991 and 2018 were retrospectively analyzed. Patients with a follow-up of less than 2 years were excluded and cure defined as being disease-free at least 5 years.100 pts were identified (median age 25 years, 89% male). 27 had distant metastases at diagnosis and 80 pts underwent upfront chemotherapy (CT). 71 pts were operated, 20 pts without prior CT). Surgery was macroscopically complete (CC0/1) in 50 pts. Hyperthermic intraperitoneal Chemotherapy (HIPEC) was administered during surgery in 15 pts 54 pts had postoperative CT and 26 pts had postoperative whole abdomino-pelvic RT (WAP-RT). After a median follow-up of 103 months (range 23-311), the median overall survival (OS) was 25 months. The 1- year, 3-year and 5-year OS rates were 90%, 35% and 4% respectively. 5 patients were considered cured after a median disease-free interval of 100 months (range 22-139). Predictive factors of cure were female sex (HR = 0.49, p = 0.014), median PCI12 (HR = 0.32, p = 0.0004), MD Anderson stage I (HR = 0.25, p 0.0001), CC0/1 (HR = 0.34, p 0.0001), and WAP-RT (HR = 0.36, p = 0.00013). HIPEC did not statistically improve survival.Cure in DSRCT is possible in 5% of patients and is best achieved combining systemic chemotherapy, complete cytoreductive surgery and WAP-RT. Despite aggressive treatment, recurrence is common and targeted therapies are urgently needed.

Sarcoma is rare and heterogenous with various subtypes having a different prognostic. Desmoid is a tumour with a local aggressiveness; GIST with KIT mutation responds massively to target treatment as IMATINIB, whereas soft tissue sarcoma and leiomyosarcoma are very aggressive with poor response to systemic therapies. Interventional radiology plays an important role in the diagnosis of sarcomas with image-guided percutaneous core needle biopsy being the most commonly used biopsy technique in the diagnosis of sarcomas. Biopsy access routes discussed with the surgeon, and skin access is tattooed. Surgery is a mainstay of sarcoma treatment; the resection can be large. Indeed, resection objective is R0 because quality of surgical margins impacts local control and survival. Radiotherapy is possible in neoadjuvant or in adjuvant treatment to improve local control rate. Recently radiotherapy enhancer injected percutaneously in soft tissue sarcoma has proven benefit in increasing the rate of R0 complete surgical resection. Several studies showed better local control rate linked with post-operative radiotherapy. In patients affected by oligometastatic disease, complete surgical resection of all metastatic sites is in fact considered the primary treatment because complete remission is critical for cure. The decision making to use local therapies is complex, depends upon diverse presentations and histologies, and should always be taken in a multidisciplinary discussion. Today, percutaneous image-guided treatments with ablation technologies (radiofrequency ablation, cryotherapy, microwaves ablation) provide high rate of durable local control for small-sized malignant deposit in many organs including lung, liver and bones. Sarcoma must be managed by multimodality treatment in expert reference centres. Such management has a considerable impact on the prognosis.

The benefits of systematic re-excision (RE) after initial unplanned excision (UE) of soft tissue sarcoma (STS) are unknown. The aim of this study was to evaluate the impact of delayed RE versus systematic RE after UE on overall survival (OS), metastatic relapse-free survival (MRFS), local relapse-free survival (LRFS), and rate of amputation. Patients who underwent complete UE, without metastasis or residual disease, for primary extremity or superficial STS between 2007 and 2013 were analyzed. The amputation rate, LRFS, MRFS, and OS were assessed in cases of systematic RE in sarcoma referral centers (Group A), systematic RE outside of community centers (Group B), or without RE (Group C). Groups A, B, and C included 300 (48.2%), 71 (11.4%), and 251 (40.4%) patients, respectively. Median follow-up was 61 months and 5-year OS was 88.4%, 87.3%, and 88% in Groups A, B, and C, respectively (p = 0.22), while 5-year MFRS was 85.4%, 86.2%, and 84.9%, respectively (p = 0.938); RE (p = 0.55) did not influence MRFS. The 5-year LRFS was 83%, 73.5%, and 63.8% in Groups A, B and C, respectively (p = 0.00001). Of the 123 local recurrences observed, 0/28, 1/15, and 5/80 patients in Groups A, B, and C, respectively, required amputation (p = 0.41). Factors influencing LRFS were adjuvant radiotherapy [hazard ratio (HR) 0.21; p = 0.0001], initial R0 resection (HR 0.24, p = 0.0001), and Group A (HR 0.44; p = 0.01). Systematic RE in sarcoma centers offers best local control but does not impact OS. Delayed RE at the time of local relapse, if any, could be an option.

Efficient pain management is essential for postoperative rehabilitation in patients undergoing a tumor resection with an immediate reconstructive surgery. Ultrasound-guided quadratus lumborum block has been described for abdominal or hip surgery, but not for concomitant surgery in the abdomen and the thigh. The paraspinous transmuscular approach has easy landmarks to perform this block. We present a case of a patient undergoing a resection of a sarcoma in the lower limb with an immediate reconstruction with a pedicled vertical designed deep inferior epigastric perforator flap, in whom a successful paraspinous transmuscular quadratus lumborum block for postoperative analgesia was performed.

11528 Background: Chordoma is a rare tumor with no approved therapy. Preclinical studies have shown expression of EGFR and activated EGFR family kinases (EGFR, HER2 and HER4). Erlotinib and other anti-EGFR agents (gefitinib and cetuximab) have shown clinical activity in advanced chordoma in single case reports or small series. We aimed to evaluate the activity of erlotinib in a larger, homogeneous series of pts with advanced chordoma. Methods: We retrospectively reviewed the electronic medical records of consecutive adult pts with advanced chordoma progressive over 6 months (+/- 2 weeks, according to RECIST 1.1), treated with erlotinib (150 mg daily) at Gustave Roussy (Villejuif, France) following multidisciplinary tumor board discussion, from January 2010 to January 2021. All cases were confirmed by an expert pathologist. Response was evaluated according to RECIST 1.1, and survival was estimated using the Kaplan-Meier method. Results: Thirty-one pts [median age : 60 years (range : 32-88), median PS : 2 (range : 1-3), 30 males)] were identified. Twenty-seven (87%) had locally advanced disease; the median number of metastatic sites was 1 (range : 1-2) in the remaining 4 pts. Primary tumor site was sacral (25), lumbar (3) or cervical (3). All pts but 6 had undergone prior surgery, and 29 (94%) had undergone radiotherapy of the primary tumor. Eight pts had received previous systemic treatments (imatinib in 4, sorafenib and regorafenib in 2 each). Best tumor response by RECIST 1.1 was PR (4 pts, 13%), SD (14 pts, 45%) or PD (13 pts, 42%). Median PFS was 6.2 months (95%CI : 4.5-9.8), and median OS was 15.9 months (95%CI : 10.6-20.2). Fourteen pts (45%) remained progression-free after 1 year, and three (10%) after two years under erlotinib. Grade 3 diarrhea occurred in 4 pts (13%) and grade 3 skin rash in 13 pts (42%). Twelve pts (39%) required dose reduction to 100 mg daily due to multiple grade 2 toxicities. Ongoing studies are exploring whether candidate biomarkers such as EGFR and HER2 expression or amplification, and their mutational status could help predicting the benefit of erlotinib in pts with advanced chordoma. Conclusions: Erlotinib has clinically meaningful but unpredictable activity in advanced chordoma. Molecular profiling would probably be of high interest in this setting. This series may serve as a benchmark for future clinical trials in chordoma.

Soft-tissue sarcoma of the limbs or the trunk wall determine a heterogeneous group of tumours that tends to receive a more individualized approach. The surgeon in charge with soft-tissue sarcoma has to be familiar with these tumours in order to deliver an adequate treatment. Most important is the initial diagnostic procedure, comprising imaging with MRI, a core needle biopsy, and in France, referral to a centre of expertise within the clinical network NETSARC. Prior to surgery, a multidisciplinary conference determines its moment and the extent of surgical resection within the frame of a multidisciplinary approach, and also plans reconstructive surgery, when needed. A standardized operative report summarizes items necessary to describe the resection quality (i.e. tumour seen, tumour infiltrated?). In multidisciplinary staff meetings, they are compared to margins measured by the pathologist on the operative specimen. Hence, resection quality is determined collegially and defined by resection type R (R0, R1, R2) as a qualitative result. The quality of resection directly determines the 5-year risk of local recurrence, estimated between 10 and 20% in specialized centres, with the objective to attain 10%. Early rehabilitation favours better functional outcome. The surgeon's experience with soft-tissue sarcoma, as part of a multidisciplinary treatment, is key in achieving the best adequacy between oncological resection and favourable functional outcome. In France, a specific university course for soft-tissue sarcoma will be set-up.

BACKGROUNDA multi-institutional nomogram for predicting disease-free survival (DFS) and overall survival (OS) in patients with primary retroperitoneal sarcoma (RPS) incorporating relevant prognostic factors not included in the American Joint Committee on Cancer staging system for soft tissue sarcoma has been reported. The authors validated this nomogram with an independent, transatlantic cohort. METHODSData from patients with RPS who were undergoing definitive resection at 1 of 6 sarcoma centers in Europe and North America (validation set) were used to validate a RPS nomogram developed from 3 other centers (development set). The nomogram incorporated 6 variables: age, tumor size, grade, histologic subtype, multifocality, and quality of surgery. Nomogram-predicted probabilities were stratified into 6 subgroups and compared with observed outcomes. Discriminative ability was quantified by Harrell C statistics. RESULTSThe validation and development sets included 631 and 523 patients, respectively, all of whom underwent surgical resection at the institutions represented. The 7-year DFS and OS rates for the validation set were 38% (95% confidence interval, 34%-43%) and 58% (95% confidence interval, 53%-63%), respectively. All 6 nomogram variables were found to be independently prognostic. The corrected Harrell C statistics concordance index values for the validation set were 0.69 for DFS and 0.73 for OS, which were similar to those for the development set, suggesting good calibration of the nomogram in the validation cohort. CONCLUSIONSThe RPS nomogram was externally validated using a larger, independent cohort. The nomogram can be generalized to patients undergoing surgery for RPS by specialized sarcoma surgeons at sarcoma centers. The nomogram provides a more individualized and disease-relevant estimation of OS compared with the American Joint Committee on Cancer classification. Cancer 2016;122:1417-1424. (c) 2016 American Cancer Society. A multi-institutional retroperitoneal sarcoma nomogram was externally validated using a large, multinational, independent cohort. The nomogram provides a more individualized and disease-relevant estimation of overall survival than the American Joint Committee on Cancer staging classification.

Well-differentiated/dedifferentiated (WD/DD) liposarcomas, the most common form of liposarcomas, constitute up to 20 % of all soft tissue sarcomas. Several oncogenes are thought to be involved in liposarcoma pathogenesis, mainly MDM2, CDK4 and HMGA2. While MDM2 inhibitors are now tested in clinical trials, a second actionable and promising target appears to be cyclin-dependent kinase 4 (CDK4), which is amplified in up to 90 % of well differentiated or dedifferentiated (WD/DD) liposarcoma. With the paucity of available therapeutic options, the inhibition of CDK4 represent a potential therapeutic option. In this paper, we review the role of CDK4/6 inhibitors in targeting the commonly identified CDK4 amplification in WD/DD liposarcoma, with an emphasis on the published and currently ongoing trials.

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.

Limb-sparing surgery in locally advanced soft tissue sarcomas (LA STS) is challenging. The aim of this study is to evaluate upfront isolated limb perfusion (ILP) in untreated patients with LA STS. All consecutive patients with LA STS of the limbs deemed borderline or unresectable and treated with upfront ILP as induction treatment between 2003 and 2016 were included. Demographic, clinical and long-term characteristics were obtained and retrospectively analyzed. 41 patients (pts), with a median age of 51 years [range 21–76], were identified (lower limb 68%, upper limb 32%). Liposarcoma and undifferentiated pleomorphic sarcoma were the most common subtypes (27% and 22%, respectively). Acute toxicities, using Wieberdink classification, were grade II (35 pts, 85%), grade III (2 pts, 5%) and no grade IV–V. Local control rate was 98%. 32 pts had limb-sparing surgery (78%). 1 pt had an early amputation due to progressive disease after ILP. 8 pts were not operated (four had RT alone, one had distant metastases, two had a complete response and one died 3 months after ILP of a pulmonary embolism). 36 pts (84%) received postoperative RT. After a median follow-up of 43 months, 18 pts (47%) relapsed. Median disease-free survival (DFS) was 6.7 years. The median overall survival (OS) was not reached. The 1-year, 5-year and 10-year DFS and OS rates were, respectively, 75%, 50% and 45%, and 90%, 63% and 55%. Upfront ILP is an efficient and well-tolerated limb-sparing procedure in borderline or unresectable LA STS without hampering OS.

The optimal treatment for pseudomyxoma peritonei (PMP) combines complete cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Yet, achieving CRS is challenging in the case of extensive involvement of the peritoneal cavity and the survival benefit in this setting remains uncertain. The present study evaluated the surgical outcomes according to the peritoneal extent.Between 1992 and 2014, 245 patients underwent CRS and HIPEC for PMP in our institution. Their characteristics were reviewed using a prospective database. Extensive PMP was defined as a peritoneal cancer index (PCI) ≥ 28. Sixty-one patients with extensive PMP were compared to 184 with non-extensive PMP.Severe complications were more frequent in the extensive group (46% vs. 23%, p 0.001) but the post-operative mortality was not significantly different (8% vs. 3%, p = 0.1). The 5-year disease-free survival reached 45% in the extensive and 78% in the non-extensive group (p 0.0001). The 5-year overall survival was 70% and 90% in the extensive and non-extensive group respectively (p 0.021).CRS with HIPEC offers prolonged survival even in the case of extensive PMP. Because of the high rate of surgical morbidity in the extensive group, patients should be carefully selected.

In bone and soft tissue sarcomas (STS), surgery was to the only local curative treatment, but recently, radiation therapy and interventional radiology has evolved to potentially curative treatment, namely in small size tumours. Indication for local treatment in STS needs validation in multidisciplinary team. Most will agree on local treatment for single metastatic location in a well-controlled disease and for no local treatment in a rapidly evolving multi-metastatic disease. The challenge is in patients who are in between, for whom benefit of disease control on overall survival should be evaluated. Local treatment has been reported beneficial in some large retrospective series, regardless of the association with chemotherapy in selected patients with oligometastatic disease. Recent technical innovation in image guidance allows to deliver local treatment through needles inserted percutaneously, and image-guided thermal ablation of small tumour is now part of the treatment armamentarium in selected oligometastatic diseases, allowing for local destruction of small tumour. Radiofrequency ablation allows to control small size STS lung metastases in roughly 90% of attempts, thus providing an efficient and low-invasive local control with preservation of organ function. Small size bone deposit can be targeted with the same rate of efficacy when tumours are small. Ablation can be used in the liver when some tumour foci become resistant to systemic therapy, namely in gastrointestinal stromal tumour patients. In addition, interventional radiology can now provide efficient and rapid pain palliation as well as bone reconstruction with the use of cementoplasty and percutaneous osteosynthesis, alongside radiation therapy which has been a long time player for pain palliation in bone metastases.

Background Low rectal cancers carry a high risk of circumferential margin involvement (CRM+). The anatomy of the lower part of the rectum and a long course of chemoradiotherapy (CRT) limit the accuracy of imaging to predict the CRM+. Additional criteria are required. Methods Eighty six patients undergoing rectal resection with a sphincter-sparing procedure after CRT for low rectal cancer between 2000 and 2013 were retrospectively reviewed. Risk factors of CRM+ and the cut-off number of risk factors required to accurately predict the CRM+ were analyzed. Results The CRM+ rate was 9.3% and in the multivariate analysis, the significant risk factors were a tumor size exceeding 3 cm, poor response to CRT and a fixed tumor. The best cut-off to predict CRM+ was the presence of 2 risk factors. Patients with 0–1 and 2–3 risk factors had a CRM+ respectively in 1.3% and 50% of cases and a 3-year recurrence rate of 7% and 35% after a median follow-up of 50 months. Conclusions Poor response, a residual tumor greater than 3 cm and a fixed tumor are predictive of CRM+. Sphincter sparing is an oncological safety procedure for patients with 0–1 criteria but not for patients with 2–3 criteria.

The peritoneal cancer index (PCI) is the main prognostic factor for establishing potentially resectable peritoneal metastases from colorectal cancer. Attempts have been made to set a PCI cutoff on which to base indications of complete cytoreductive surgery (CCRS) with hyperthermic intraperitoneal chemotherapy (HIPEC), but none have reached consensus. The aim of this study was to investigate the relation between the PCI and overall survival (OS).We included all consecutive patients homogeneously treated with CCRS and HIPEC between 2003 and 2012. The PCI was calculated at the end of the surgical procedure. The correlation between the PCI and OS was studied using statistical modeling from the simplest to the most complex methods (including linear, quadratic, cubic, and spline cubic). These models were compared by Akaike's information criteria (AIC).For the 173 treated patients, 5-year OS reached 41 %. The mean PCI was 10.2 (±6.8). The linear model was the most appropriate to relate the PCI to OS as confirmed with the AIC scoring system. In multivariate analysis, the PCI was confirmed as being the most important prognostic factor (hazard ratio = 1.1 for each supplementary point, p0.0001).There is a perfect linear correlation between the PCI and OS, which precludes setting a unique PCI cutoff for CCRS + HIPEC. Overall, CCRS + HIPEC is generally indicated for PCI12 and contraindicated for PCI17. Between 12 and 17, other parameters have to be taken into account, such as the presence of extraperitoneal metastases, general performance status, and chemosensitivity.

Background Perineal soft tissue tumors are rare, so that little is known about their management and the outcome of treatment. Objective The aim of this study is to describe the presentation, management, and outcome of the surgical treatment of soft tissue tumors and to provide a final decision algorithm. Design This is a retrospective study. Settings The study was conducted in a single tertiary care hospital with a dedicated unit on sarcoma. Patients Fifty-one consecutive patients from 1998 to 2013 were included. Main outcome measures The primary outcomes measured are patient demographics, treatment decisions, and outcome of surgical treatment. Results Forty-nine patients presented with a primary soft tissue tumor, and 2 underwent simple excisions for isolated metastases. The median tumor size was 75 mm (50-110). Symptoms were nonspecific, and MRI had insufficient specificity for malignancy so that a preoperative biopsy was systematically performed according to European Society for Medical Oncology and National Comprehensive Cancer Network soft tissue tumor guidelines. Six benign soft tissue tumors (3 lipomas, 3 leiomyomas), 16 intermediate soft tissue tumors (12 aggressive angiomyxoma, 4 desmoid tumors), and 27 sarcomas were identified. Treatments and surgery were tailored from the beginning according to histology. All but 1 benign soft tissue tumor were treated by 'shelling out.' Aggressive angiomyxoma were treated with en bloc resection sparing uninvolved organs. Nonsurgical treatments were our first choice for desmoid tumors. Wide en bloc surgery was planned for all sarcomas (n = 27) after the induction treatment for 16 patients (chemotherapy, n = 12; radiotherapy, n = 4). In the sarcoma group, the 5-year estimated metastasis-free, local recurrence-free, and overall survival rates were 68.1% (95% CI, 50.7-91.5), 84.7% (95% CI, 66.7-100), and 85.7% (95% CI, 71.8-100). In the benign and intermediate tumor groups, there were no deaths, local recurrences, or progression. Limitations This study was limited by the small number of patients, given the rarity of this disease in the perineum. Conclusion We provide useful indications for the best strategy necessary to treat these rare tumors located in a complex site.

The main prognostic factors after complete cytoreductive surgery (CCRS) of colorectal peritoneal carcinomatosis (PC) followed by intraperitoneal chemotherapy (IPC) are completeness of the resection and extent of the disease. This study aimed to determine a threshold value above which CCRS plus IPC may not offer survival benefit compared with systemic chemotherapy. Between March 2000 and May 2010, 180 patients underwent surgery for PC from colorectal cancer with intended performance of CCRS plus IPC. Among the 180 patients, CCRS plus IPC could be performed for 139 patients (curative group, 77 %), whereas it could not be performed for 41 patients (palliative group, 23 %). The two groups were comparable in terms of age, gender, primary tumor characteristics, and pre- and postoperative systemic chemotherapy. The mean peritoneal cancer index (PCI) was lower in the curative group (11 ± 7) than in the palliative group (23 ± 7) (p

Background To analyse the natural history of extra-abdominal wall desmoid-type fibromatosis (DF) and compare outcome in patients who underwent initial surgery with those who did not. Patients and methods All consecutive patients affected by primary sporadic extra-abdominal wall DF observed between January 1992 and December 2012 were included. Patients were divided into surgical (SG) or non-surgical groups (NSG) according to initial treatment. Relapse free survival was calculated for SG, and crude cumulative incidence (CCI) of switching to surgery or other treatments for NSG. Results 216 patients were identified, 94 in SG (43%), 122 in NSG (57%). A shift towards a more systematic use of a conservative approach (78% of all comers) was observed in the latter years (2006–2012), although a small proportion of patients (28%) had been offered the conservative strategy even in the early period (1992–2005). Median follow-up (FU) was 49 mo. (interquartile (IQ), 20–89 mo.), 76 months for SG and 39 months for NSG. 5-year relapse-free survival (RFS) for SG was 80% (95% confidence interval (CI), 72–89%). For the NSG, 5-year CCI of switching to surgery was 5% (95% CI: 1.7%, 14%), and 51% to other treatments (95% CI: 41%, 65%). 27 (20%) NSG patients underwent spontaneous regression. Conclusion A non-surgical approach to extra-abdominal wall DF allowed surgery to be avoided in the majority of patients. This approach can be safely proposed and surgery offered as an option in selected cases.

Peritoneal metastases (PM) occur in 3.4-6.3% after curative surgery for non-metastatic colorectal cancer. Systematic "2nd look" surgery helps overcoming the diagnostic problem but can be only proposed to selected patients. The aim of this study was to update the knowledge on risk factors of developing PM after curative surgery for colorectal cancer.A systematic review of the literature published between 2011 and 2016 was made, searching for all clinical studies reporting the incidence of recurrent PM after curative surgery for colorectal cancer and factors associated with the primary tumour that were likely to influence this recurrence rate.Seven new clinical studies were considered informative for risk factors and added to the 16 reviewed in 2013. Even if the level of evidence was low, data suggested rates of recurrent PM at 1 year between 54% and 71% after completely resected synchronous PM, between 62% and 71% after resection of isolated synchronous ovarian metastases, of 27% after surgery for a perforated primary tumour, of 16% after surgery for a pT4 tumour, and between 11% and 36% after surgery for a mucinous histological subtype. No new risk factor was identified.Evidence regarding the incidence of recurrent PM after curative surgery for colorectal cancer is poor. Situations at higher risk of recurrent PM are synchronous PM, synchronous isolated ovarian metastases, perforated primary tumour with serosa invasion and mucinous histological subtype.

To investigate the safety of radical resection for retroperitoneal sarcoma (RPS).The surgical management of RPS frequently involves complex multivisceral resection. Improved oncologic outcomes have been demonstrated with this approach compared to marginal excision, but the safety of radical resection has not been shown in a large study population.The Transatlantic Retroperitoneal Sarcoma Working Group (TARPSWG) is an international collaborative of sarcoma centers. A combined experience of 1007 consecutive resections for primary RPS from January 2002 to December 2011 was studied retrospectively with respect to adverse events. A weighted organ score was devised to account for differences in surgical complexity. Univariate and multivariate logistic regression analyses were performed to investigate associations between adverse events and number and patterns of organs resected. Associations between adverse events and overall survival, local recurrence, and distant metastases were investigated.Severe postoperative adverse events (Clavien-Dindo ≥3) occurred in 165 patients (16.4%) and 18 patients (1.8%) died within 30 days. Significant predictors of severe adverse events were age (P = 0.003), transfusion requirements (P0.001), and resected organ score (P = 0.042). Resections involving pancreaticoduodenectomy, major vascular resection, and splenectomy/pancreatectomy were found to entail higher operative risk (odds ratio1.5). There was no impact of postoperative adverse events on overall survival, local recurrence, or distant metastases.A radical surgical approach to RPS is safe when carried out at a specialist sarcoma center. High-risk resections should be carefully considered on an individual basis and weighed against anticipated disease biology. There appears to be no association between surgical morbidity and long-term oncologic outcomes.