Improved nationwide survival of sarcoma patients with a network of reference centers.

BACKGROUND: We investigated the impact of the implementation of a network of reference centers for sarcomas (NETSARC) on the care and survival of sarcoma patients in France since 2010. PATIENTS AND METHODS: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDTBs), funded by the French National Cancer Institute (INCa) since 2010. Its aims are to improve the quality of diagnosis and care of sarcoma patients. Patients' characteristics, treatments, and outcomes are collected in a nationwide database. The objective of this analysis was to compare the survival of patients in three periods: 2010-2012 (non-exhaustive), 2013-2015, and 2016-2020. RESULTS: A total of 43 975 patients with sarcomas, gastrointestinal stromal tumors (GISTs), or connective tissue tumors of intermediate malignancy were included in the NETSARC+ database since 2010 (n = 9266 before 2013, n = 12 274 between 2013 and 2015, n = 22 435 in 2016-2020). Median age was 56 years, 50.5% were women, and 13.2% had metastasis at diagnosis. Overall survival was significantly superior in the period 2016-2020 versus 2013-2015 versus 2010-2012 for the entire population, for patients >18 years of age, and for both metastatic and non-metastatic patients in univariate and multivariate analyses (P < 0.0001). Over the three periods, we observed a significantly improved compliance to clinical practice guidelines (CPGs) nationwide: the proportion of patients biopsied before surgery increased from 62.9% to 72.6%; the percentage of patients presented to NETSARC MDTBs before first surgery increased from 31.7% to 44.4% (P < 0.0001). The proportion of patients with R0 resection on first surgery increased (from 36.1% to 46.6%), while R2 resection rate decreased (from 10.9% to 7.9%), with a better compliance and improvement in NETSARC centers. CONCLUSIONS: The implementation of the national reference network for sarcoma was associated with an improvement of overall survival and compliance to guidelines nationwide in sarcoma patients. Referral to expert networks for sarcoma patients should be encouraged, though a better compliance to CPGs can still be achieved.

Pre-anaesthesia assessment in cataract surgery: Recommendations from the SEDAR Working Group.

INTRODUCTION AND OBJECTIVES: Cataract surgery is one of the most common procedures in outpatient surgery units. The use of information and communication technologies (ICT) in clinical practice and the advent of new health scenarios, such as the Covid pandemic, have driven the development of pre-anaesthesia assessment models that free up resources to improve access to cataract surgery without sacrificing patient safety. The approach to cataract surgery varies considerably among public, subsidised and private hospitals. This raises the need for guidelines to standardise patient assessment, pre-operative tests, management of background medication, patient information and informed consent. RESULTS: In this document, the SEDAR Clinical Management Division together with the Major Outpatient Surgery Division SEDAR Working Group put forward a series of consensus recommendations on pre-anaesthesia testing based on the use of ITCs, health questionnaires, patient information and informed consent supervised and evaluated by an anaesthesiologist. CONCLUSIONS: This consensus document will effectivise pre-anaesthesia assessment in cataract surgery while maintaining the highest standards of quality, safety and legality.

Nivolumab in patients with advanced renal cell carcinoma in France: interim results of the observational, real-world WITNESS study.

BACKGROUND: Nivolumab is the first immune checkpoint inhibitor approved in Europe for the treatment of advanced renal cell carcinoma (aRCC) in patients resistant to prior antiangiogenic therapy. WITNESS is an ongoing, prospective, observational study designed to evaluate the effectiveness and safety of nivolumab in patients with aRCC treated in real life (or routine practice) in France (ClinicalTrials.gov identifier: NCT03455452). PATIENTS AND METHODS: This study includes adult patients with a confirmed diagnosis of aRCC who have initiated nivolumab after 1-2 prior lines of antiangiogenic therapy. Endpoints include overall survival (OS), progression-free survival (PFS), duration of treatment (DOT), duration of response (DOR), overall response rate (ORR), subgroup analyses, and treatment-related adverse events (TRAEs). Results after a median follow-up of 12.3 months are presented here. RESULTS: A total of 325 patients with aRCC were included, of whom 38.2% had a Karnofsky score <80, 77.8% received nivolumab as second-line therapy, and 69.5% had undergone a previous nephrectomy. In the overall population, median OS was 20.5 [95% confidence interval (CI) 17.6-25.0] months and median PFS was 5.2 (95% CI 4.5-5.9) months. ORR was 34.5%, median DOT was 3.8 months, and median DOR was 16.5 months. Nivolumab was effective in different subgroups including patients with bone or glandular metastases and those receiving baseline corticosteroids. Moreover, effectiveness was observed irrespective of prior nephrectomy and line of treatment. No new safety signals were identified; TRAEs of any grade were reported in 32.0% of patients, grade ≥3 and serious TRAEs in 11.1% each, and TRAEs leading to discontinuation in 8.9%. CONCLUSIONS: Preliminary results of the ongoing WITNESS study confirm the real-world effectiveness and safety of nivolumab monotherapy in previously treated patients with aRCC. Treatment benefits were similar to those observed in the pivotal phase III CheckMate 025 randomized clinical trial, despite a broader, real-life study population.

Cerebral venous thrombosis in adults: a case series of 35 patients from a tertiary hospital.

OBJECTIVE: To describe the baseline characteristics, clinical presentation, imaging tests and outcomes, and identify potential prognostic factors in a cohort of patients diagnosed with cerebral venous thrombosis (CVT). PATIENTS AND METHODS: This retrospective, single-center, observational study included adult patients diagnosed with CVT from January 2016 to December 2020. The variables were reviewed using electronic medical records. RESULTS: A total of 35 patients were included, with a median age at diagnosis of 50.3 (+/- 17.8) years, and the majority being women (74.4%). Nearly 95% of the patients presented at least one risk factor for the development of CVT. Heparins were used for the acute phase in 97.1% of cases, with 75% of those being low molecular weight heparins.During the first two weeks, a compound event (death, intensive care unit admission, National Institute of Health Stroke Scale at discharge >3, CVT recurrence, major bleeding, or the presence of complications) occurred in 28.6% of patients (10 patients).Over the mean follow-up period of 3.3 years, 14.3% of the patients died (with only one death attributed to CVT), one patient experienced major bleeding, and no patients had a recurrence of CVT. CONCLUSIONS: In our cohort, CVT predominantly affected young women with at least one risk factor for its development. The presence of edema on CT and corticosteroid treatment were associated with a poor short-term prognosis. However, we observed a favorable long-term prognosis in terms of mortality, recurrence, and bleeding.

Regorafenib in patients with relapsed advanced or metastatic chordoma: results of a non-comparative, randomised, double-blind, placebo-controlled, multicentre phase II study.

BACKGROUND: REGOBONE multicohort study explored the efficacy and safety of regorafenib for patients with advanced bone sarcomas; this report details the cohort of patients with relapsed advanced or metastatic chordoma. METHODS: Patients with relapsed chordoma progressing despite 0-2 prior lines of systemic therapy, were randomised (2 : 1) to receive regorafenib (160 mg/day, 21/28 days) or placebo. Patients on placebo could cross over to receive regorafenib after centrally-confirmed progression. The primary endpoint was the progression-free rate at 6 months (PFR-6) (by RECIST 1.1). With one-sided α of 0.05, and 80% power, at least 10/24 progression-free patients at 6 months (PFR-6) were needed for success. RESULTS: From March 2016 to February 2020, 27 patients were enrolled. A total of 23 patients were assessable for efficacy: 7 on placebo, 16 on regorafenib, 16 were men, median age was 66 (32-85) years. At 6 months, in the regorafenib arm, 1 patient was not assessable, 6/14 were non-progressive (PFR-6: 42.9%; one-sided 95% CI = 20.6) 3/14 discontinued regorafenib due to toxicity; and in the placebo arm, 2/5 patients were non-progressive (PFR-6: 40.0%; one-sided 95% CI = 7.6), 2 were non-assessable. Median progression-free survival was 8.2 months (95% CI 4.5-12.9 months) on regorafenib and 10.1 months (95% CI 0.8 months-non evaluable [NE]) on placebo. Median overall survival rates were 28.3 months (95% CI 14.8 months-NE) on regorafenib but not reached in placebo arm. Four placebo patients crossed over to receive regorafenib after centrally-confirmed progression. The most common grade ≥3 regorafenib-related adverse events were hand-foot skin reaction (22%), hypertension (22%), pain (22%), and diarrhoea (17%), with no toxic death. CONCLUSION: This study failed to show any signal of benefit for regorafenib in patients with advanced/metastatic recurrent chordoma.

Patterns of care and outcomes of 417 patients with METAstatic SYNovial sarcoma (METASYN): real-life data from the French Sarcoma Group (FSG).

BACKGROUND: Synovial sarcoma (SS) occurs in both adult and pediatric patients. The primary aim of this study is to describe the outcomes, prognostic factors, and treatment of patients with metastatic SS within a nationwide cohort. PATIENTS AND METHODS: All pediatric and adult patients with metastatic SS are registered in the French Sarcoma Group database. Data were collected from the national database https://conticabase.sarcomabcb.org/ up to March 2020. Descriptive and comparative analyses were conducted using SAS 9.4 and Stata Special Edition 16.1 software. RESULTS: Between January 1981 and December 2019, 417 patients with metastatic SS from 17 French sarcoma centers were included, including 64 (15.3%) under the age of 26 years. Median age was 42.5 years (range 9-87 years). The metastases were synchronous (cohort 1) or metachronous (cohort 2) in 18.9% (N = 79) and 81.1% (N = 338) patients, respectively. Median overall survival (OS) from the date of metastasis was 22.3 months (95% confidence interval 19.7-24.1 months). First-line chemotherapy without ifosfamide and/or doxorubicin was unfavorable for progression-free survival and OS (P < 0.001). Concerning cohort 1, young age, surgery of the primary tumor, and single metastatic site were independent favorable prognostic factors for OS. In cohort 2, surgery within an expert French Sarcoma Group center, absence of chemotherapy in the perioperative setting, the lungs as a single metastatic site, time to first metastasis >12 months, local therapy, and ifosfamide in the first metastatic line were independent favorable prognostic factors. CONCLUSIONS: The outcome of patients with metastatic SS is influenced by local treatment, management in reference centers, and cytotoxic treatments given in the perioperative and metastatic setting.

[Alveolo-interstitial pneumonia due to Temozolamide]. / Pneumonie alvéolo-interstitielle au témozolomide.

INTRODUCTION: Temozolomide is an alkylating agent approved for treatment of glioblastoma in association with radiotherapy. CASE REPORT: We report the case of a 56 year old woman presenting with alveolo-interstitial pneumonia after treatment with Temozolomide. Initially she received induction treatment with Temozolomide and concomitant radiotherapy for bifocal high grade glioblastoma. A month later she received, as scheduled, the first course of Temozolomide maintenance chemotherapy. Grade II dyspnoea developed a few days later. High resolution computed tomography showed alveolo-interstitial opacities with basal predominance, associated with alveolar nodules. Broncho-alveolar lavage showed a lymphocytosis. No bacteria were isolated from microbiological samples. A final diagnosis of drug-induced pneumonia was based on the time sequence and absence of other causes. CONCLUSION: There is little literature concerning the pulmonary toxicity of Temozolomide. However, our case report of drug-induced pneumonia and similar observations in the databases of regional pharmacovigilance centres suggest that this side effect should be included in the summary of product characteristics.

Understanding the planar tetracoordinate carbon atom: spiropentadiene dication.

The atoms in molecule theory shows that the spiropentadiene dication has a planar tetracoordinate carbon (ptC) atom stabilized mainly through the sigma bonds and this atom has a negative charge. The bonds to the ptC atom have less covalent character than the central carbon from neutral spiropentadiene. The total positive charge is spread along the structure skeleton. The analysis of the potential energy surface shows that the dication spiropentadiene has a 2.3 kcal/mol activation barrier for ring opening.

Neutral structures with a planar tetracoordinated carbon based on spiropentadiene analogues.

Neutral hydrocarbon structures containing a planar tetracoordinated carbon atom are proposed on the basis of quantum chemical calculations. The planarity at the central carbon atom is achieved by using aromaticity for stabilizing a positively charged core moiety that contains the planar atom. This charge is compensated by negatively charged cyclopentadienyl rings fused on the structure, leading to neutral structures. These are found to be stable from a dynamic point of view and are potentially synthesizable through carbene chemistry. These structures can lead to new breakthroughs in the chemical structure theory. A family of species derived from this model is also presented.