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Background and Aims: Alveolar soft part sarcoma (ASPS) is an ultra-rare chemo-resistant sarcoma in children, occurring preferentially in young adults. We aimed to describe and compare its clinical presentation and behaviour in children and young adults to determine whether the same therapeutic strategy should be addressed for both populations., Methods: National retrospective multicentre study of children (0-18 years) vs. young adults (19-30 years) included in the "ConticaBase" sarcoma database, treated for ASPS between 2010 and 2019 with pathology reviewed via the NETSARC + network., Results: Overall, 45 patients were identified, 19 children (42%) and 26 young adults (58%). All ASPS diagnoses were confirmed with TFE3 rearrangement by immunohistochemistry or FISH. All clinical characteristics were balanced between both populations with frequent metastases at diagnosis (8/19 vs. 10/26). The therapeutic strategy was based on surgery (17/19 vs. 21/26), radiotherapy (8/19 vs. 12/26) ± systemic treatment (8/19 vs. 9/26). In patients with initially localized disease, metastatic relapse occurred only in adults (8/16), whereas metastatic progression was present in both metastatic groups (5/8 vs. 8/10). After a median follow-up of 5.2 years (range, 0.2-12.2), 5-year EFS was 74% [95%CI, 56-96] vs. 47% [30-74] (p = 0.071) respectively, and 5-year OS was 95% [85-100] vs. 85% [70-100] (p = 0.84). For localized tumours, 5-year MFS was 100% [100-100] vs. 60% [39-91] (p = 0.005). The 5-year OS of all patients with metastasis at diagnosis was 80.2% (62.2%-100%)., Conclusions: ASPS appears to have the overall same clinical characteristics, but a more aggressive behaviour in young adults than in children. However, despite frequent metastases at diagnosis, long-term survival is high in both groups. Overall, the same therapeutic strategies may be considered for both populations., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Desmoid fibromatosis is a rare locally aggressive soft tissue tumor that is characterized as benign as it cannot metastasize. It was managed until recently like sarcomas, i.e with radical surgical resection combined or not with radiotherapy. However, this approach was associated with a high rate of recurrence and significant morbidity. The management of this disease has progressively changed to a more conservative approach given the fact that desmoid fibromatosis may spontaneously stop to grow or even shrink in more than half of the cases. Should treatment be required, recent guidelines recommend choosing between systemic therapies, which include principally chemotherapy and tyrosine kinase inhibitors, and local treatments. And this is where the interventional radiologist may have an important role to treat the disease. Various ablation modalities have been reported in the literature to treat desmoid fibromatosis, notably high-intensity focused ultrasound and cryoablation. Results are promising and cryoablation is now mentioned in recent guidelines. The interventional radiologist should nevertheless apprehend the disease in its globality to understand the place of percutaneous treatments among the other therapeutic options. The goal of this review is therefore to present and discuss the role of interventional radiology (IR) in the management of DF., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology.)

Background: Perivascular epithelioid cell neoplasms (PEComas) encompass a heterogeneous family of mesenchymal tumors. Previously described clinicopathologic features aimed at distinguishing benign from malignant variants but lacked prognostic value., Methods: This retrospective analysis examined clinicopathologic data from patients who had localized PEComa across French Sarcoma Network centers. The authors analyzed 12 clinicopathologic features in a Cox proportional hazard framework to derive a multivariate prognostic risk model for event-free survival (EFS). They built the PEComa prognostic score (PEC-PRO), in which scores ranged from 0 to 5, based on the coefficients of the multivariate model. Three groups were identified: low risk (score = 0), intermediate risk (score = 1), and high risk (score ≥ 2)., Results: Analyzing 87 patients who had a median 46-month follow-up (interquartile range, 20-74 months), the median EFS was 96.5 months (95% confidence interval [CI], 47.1 months to not applicable), with 2-year and 5-year EFS rates of 64.7% and 58%, respectively. The median overall survival was unreached, with 2-year and 5-year overall survival rates of 82.3% and 69.3%, respectively. The simplified Folpe classification did not correlate with EFS. Multivariate analysis identified three factors affecting EFS: positive surgical margins (hazard ratio [HR], 5.17; 95% CI, 1.65-16.24; p = .008), necrosis (HR, 3.94; 95% CI, 1.16-13.43; p = .030), and male sex (HR, 3.13; 95% CI, 1.19-8.27; p = 0.023). Four variables were retained in the prognostic model. Patients with low-risk PEC-PRO scores had a 2-year EFS rate of 93.7% (95% CI, 83.8%-100.0%), those with intermediate-risk PEC-PRO scores had a 2-year EFS rate of 67.4% (95% CI, 53.9%-80.9%), and those with high-risk PEC-PRO scores had a 2-year EFS rate of 2.3% (95% CI, 0.0%-18.3%)., Conclusions: The PEC-PRO score reliably predicts the risk of postoperative recurrence in patients with localized PEComa. It has the potential to improve follow-up strategies but requires validation in a prospective trial., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Purpose: This study investigates changes in CD8+ cells, CD8+/Foxp3 ratio, HLA I expression, and immune coregulator density at diagnosis and upon neoadjuvant chemotherapy (NACT), correlating changes with clinical outcomes., Experimental Design: Multiplexed immune profiling and cell clustering analysis were performed on paired matched ovarian cancer samples to characterize the immune tumor microenvironment (iTME) at diagnosis and under NACT in patients enrolled in the CHIVA trial (NCT01583322)., Results: Several immune cell (IC) subsets and immune coregulators were quantified pre/post-NACT. At diagnosis, patients with higher CD8+ T cells and HLA I+-enriched tumors were associated with a better outcome. The CD8+/Foxp3+ ratio increased significantly post-NACT in favor of increased immune surveillance, and the influx of CD8+ T cells predicted better outcomes. Clustering analysis stratified pre-NACT tumors into four subsets: high Binf, enriched in B clusters; high Tinf and low Tinf, according to their CD8+ density; and desert clusters. At baseline, these clusters were not correlated with patient outcomes. Under NACT, tumors were segregated into three clusters: high BinfTinf, low Tinf, and desert. The high BinfTinf, more diverse in IC composition encompassing T, B, and NK cells, correlated with improved survival. PDL1 was rarely expressed, whereas TIM3, LAG3, and IDO1 were more prevalent., Conclusions: Several iTMEs exist during tumor evolution, and the NACT impact on iTME is heterogeneous. Clustering analysis of patients unravels several IC subsets within ovarian cancer and can guide future personalized approaches. Targeting different checkpoints such as TIM3, LAG3, and IDO1, more prevalent than PDL1, could more effectively harness antitumor immunity in this anti-PDL1-resistant malignancy., (©2024 The Authors; Published by the American Association for Cancer Research.)

Introduction: Cervical cancer is a global public health concern. Despite ESGO recommendations and FIGO classification changes, management of locally advanced cervical cancer (LACC) remains debated in France. Our study aimed to review LACC treatment practices and assess adherence to ESGO recommendations among different practitioners., Methods: From February 2021 to August 2022, we conducted a survey among gynecologic oncology surgeons, radiation oncologists, and medical oncologists practicing in France and managing LACC (FIGO stages IB3-IVA) according to the 2018 FIGO classification. We analyzed responses against the 2018 ESGO recommendations as a "gold standard.", Results: Among 115 respondents (56% radiation oncologists, 30% surgeons, 13% medical oncologists), 48.6% of gynecologic surgeons didn't perform para-aortic lymphadenectomy (PAL) with significant radiologic pelvic involvement. PAL, when indicated by PET-CT, was more common in university hospitals (66.7% of surgeons). Surgeons in university hospitals also followed ESGO recommendations more closely. Overall, compliance with all ESGO recommendations was low: 5.7% of surgeons, 21.5% of radiation oncologists, and 60% of medical oncologists. Prophylactic para-aortic irradiation, per ESGO, was more frequent in comprehensive cancer centers (52% of radiation oncologists)., Conclusion: Adherence to ESGO recommendations for LACC treatment appears low in France, particularly in surgery, with limited PAL in cases of lymph node negativity on PET-CT. However, these recommendations are more often followed by surgeons in university hospitals and radiation oncologists in cancer centers. Adherence to these recommendations may impact patient survival and warrants evaluation of care quality, justifying the organization of LACC management in expert centers., Competing Interests: Declaration of competing interest None., (© 2024 Published by Elsevier Ltd.)

Aims: Characteristics, management, and outcomes of patients with active cancer admitted for cardiogenic shock remain largely unknown. This study aimed to address this issue and identify the determinants of 30-day and 1-year mortality in a large cardiogenic shock cohort of all aetiologies., Methods and Results: FRENSHOCK is a prospective multicenter observational registry conducted in French critical care units between April and October 2016. 'Active cancer' was defined as a malignancy diagnosed within the previous weeks with planned or ongoing anticancer therapy. Among the 772 enrolled patients (mean age 65.7 ± 14.9 years; 71.5% male), 51 (6.6%) had active cancer. Among them, the main cancer types were solid cancers (60.8%), and hematological malignancies (27.5%). Solid cancers were mainly urogenital (21.6%), gastrointestinal (15.7%), and lung cancer (9.8%). Medical history, clinical presentation, and baseline echocardiography were almost the same between groups. In-hospital management significantly differed: patients with cancers received more catecholamines or inotropes (norepinephrine 72% vs. 52%, P = 0.005 and norepinephrine-dobutamine combination 64.7% vs. 44.5%, P = 0.005), but had less mechanical circulatory support (5.9% vs. 19.5%, P = 0.016). They presented a similar 30-day mortality rate (29% vs. 26%) but a significantly higher mortality at 1-year (70.6% vs. 45.2%, P < 0.001). In multivariable analysis, active cancer was not associated with 30-day mortality but was significantly associated with 1-year mortality in 30-day survivors [HR 3.61 (1.29-10.11), P = 0.015]., Conclusion: Active cancer patients accounted for almost 7% of all cases of cardiogenic shock. Early mortality was the same regardless of active cancer or not, whereas long-term mortality was significantly increased in patients with active cancer., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Renal medullary carcinoma (RMC) is an aggressive tumour driven by bi-allelic loss of SMARCB1 and tightly associated with sickle cell trait. However, the cell-of-origin and oncogenic mechanism remain poorly understood. Using single-cell sequencing of human RMC, we defined transformation of thick ascending limb (TAL) cells into an epithelial-mesenchymal gradient of RMC cells associated with loss of renal epithelial transcription factors TFCP2L1, HOXB9 and MITF and gain of MYC and NFE2L2-associated oncogenic and ferroptosis resistance programs. We describe the molecular basis for this transcriptional switch that is reversed by SMARCB1 re-expression repressing the oncogenic and ferroptosis resistance programs leading to ferroptotic cell death. Ferroptosis resistance links TAL cell survival with the high extracellular medullar iron concentrations associated with sickle cell trait, an environment propitious to the mutagenic events associated with RMC development. This unique environment may explain why RMC is the only SMARCB1-deficient tumour arising from epithelial cells, differentiating RMC from rhabdoid tumours arising from neural crest cells., (© 2023. The Author(s).)

Following chemotherapy, a mediastinal germ cell tumor can lead to a mature teratoma that is composed of tissues derived from all three germ layers. Although teratoma is usually curable, in rare cases it can give rise to various somatic tumors and exceptionally it undergoes melanocytic neuroectodermal tumor (MNT) transformation, a process that is not well-described. We report a patient with a postchemotherapy thymic teratoma associated with an MNT component who, 10 years later, additionally presented a vertebral metastasis corresponding to an anaplastic MNT. Using exome sequencing of the mature teratoma, the MNT and its metastatic vertebral anaplastic MNT components, we identified 19 somatic mutations shared by at least two components. Six mutations were common to all three components, and three of them were located in the known cancer-related genes KRAS (p.E63K), TP53 (p.P222X), and POLQ (p.S447P). Gene set enrichment analysis revealed that the melanoma tumorigenesis pathway was enriched in mutated genes including the four major driver genes KRAS , TP53 , ERBB4 , and KDR , indicating that these genes may be involved in the development of the anaplastic MNT transformation of the teratoma. To our knowledge, this is the first molecular study realized on MNT. Understanding the clinicopathological and molecular characteristics of these tumors is essential to better understand their development and to improve therapeutics., (© 2023 Mayeur et al.; Published by Cold Spring Harbor Laboratory Press.)

Background: CIC-rearranged sarcomas (CIC-RS) represent the most frequent subset of "Ewing-like" undifferentiated small round cell sarcomas. These tumors tend to be more aggressive than Ewing sarcomas. Moreover, treatment strategy can differ according to teams. The primary aim of this retrospective study was to describe the characteristics, treatments, and outcome for patients with CIC-RS included in the French NETSARC+ database., Methods: Pediatric and adult patients from 13 French centers with a diagnosis of CIC-RS were registered from October 2008 to March 2021. Patients and tumors characteristics were collected from the national network NETSARC+ database (http://netsarc.sarcomabcb.org). CIC-RS diagnosis was pathologically and molecularly confirmed with a central review by expert pathologists. Two groups of patients were studied: those treated as classical Ewing sarcomas (cohort EwS) and those treated as high-grade soft tissue sarcomas (cohort STS) according to ESMO and/or EpSSG guidelines. Survival was calculated using the Kaplan-Meier method and the log-rank test was used to compare survival., Results: Among 79 patients, the male/female sex ratio was 0.7 and the median age at diagnosis was 27 years (range 2-87). With a median follow-up of 37 months, 39 patients died of the disease. Median overall survival from diagnosis was 18 months, with no significant difference between both cohorts (p = 0.9). Nevertheless, when focusing on patients with metastatic disease at diagnosis (N = 21), all patients from cohort STS died of disease while some patients from cohort EwS were still alive and in complete remission., Conclusion: FSG experience confirms the aggressive clinical course of CDS patients regardless of chemotherapy regimen., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Aim: The oral anti-angiogenic therapy nintedanib prolongs progression-free survival (PFS) when combined with chemotherapy after primary surgery for advanced epithelial ovarian cancer. The randomized phase II CHIVA trial evaluated the impact of combining nintedanib with neoadjuvant chemotherapy (NACT) for epithelial ovarian cancer., Methods: Patients with newly diagnosed unresectable FIGO stage IIIC-IV epithelial ovarian cancer received 3-4 cycles of carboplatin plus paclitaxel every 3 weeks as NACT before interval debulking surgery (IDS), followed by 2-3 post-operative cycles. Patients were randomized 2:1 to receive either nintedanib 200 mg twice daily or placebo on days 2-21 every 3 weeks during NACT (omitting peri-operative cycles), and then as maintenance therapy for up to 2 years. The primary endpoint was PFS., Results: Between January 2013 and May 2015, 188 patients were randomized (124 to nintedanib, 64 to placebo). PFS was significantly inferior with nintedanib (median 14.4 versus 16.8 months with placebo; hazard ratio 1.50, p = 0.02). Overall survival (OS) was also inferior (median 37.7 versus 44.1 months, respectively; hazard ratio 1.54, p = 0.054). Nintedanib was associated with increased toxicity (grade 3/4 adverse events: 92% versus 69%, predominantly hematologic and gastrointestinal), lower response rate by RECIST (35% versus 56% before IDS), and lower IDS feasibility (58% versus 77%) versus placebo., Conclusions: Adding nintedanib to chemotherapy and in maintenance as part of NACT for advanced epithelial ovarian cancer cannot be recommended as it increases toxicity and compromises chemotherapy efficacy (IDS, PFS, OS)., Clinicaltrials: govregistration: NCT01583322., Competing Interests: Declaration of Competing Interest Gwénaël Ferron: Advisory boards (Clovis, AstraZeneca, GSK, MSD, Roche, RanD Biotech, Olympus), lectures/symposia (AstraZeneca, Clovis, GSK, MSD, PharmaMar). Nicolas Delanoy: Advisory boards/honoraria (GSK, AstraZeneca, MSD, Clovis Oncology). Florence Joly: Advisory boards (Clovis, AstraZeneca, GSK, MSD, Seagen), lectures/symposia (AstraZeneca, Clovis, GSK, MSD); non-gynecology: Ipsen, Janssen, Sanofi, Bayer, Astellas, Pfizer, Amgen. Alain Lortholary: Advisory board fees (AstraZeneca, MSD Tesaro), speaker honoraria (Clovis Oncology, Roche), congress participation (Novartis, Pfizer, MSD, Lilly, Roche), member of CS3 sein UNICANCER. Benoît You: Consulting (MSD, AstraZeneca, GSK–Tesaro, Bayer, Roche/Genentech, ECS Progastrin, Novartis, LEK, Amgen, Clovis Oncology, Merck Serono, BMS, Seagen, Myriad). Nadine Dohollou: Consulting/expert (Daiichi, Lilly, Roche, Seagen), conferences/training (Daiichi, Lilly, Roche, Seagen), research grants/clinical trials (AstraZeneca, BMS, Boehringer Ingelheim, Genomic Health, Lilly, MSD, Novartis, Pfizer, Roche). Anne Floquet: Advisory boards (MSD, AstraZeneca, GSK, Clovis Oncology), congress participation (AstraZeneca, GSK, MSD, PharmaMar, Roche). Michel Fabbro: AstraZeneca, GSK, Clovis. Jérôme Alexandre: AstraZeneca, GSK, Clovis, MSD, Eisai, Novartis. Isabelle Ray-Coquard: Advisory/consultancy (Amgen, AstraZeneca, Clovis Oncology, Genmab, GSK, ImmunoGen, Mersana, Deciphera, Novocure, Eisai, Sutro Pharma, Merck Sharp & Dohme, Pfizer/Merck Serono, PharmaMar, Roche), research grant/funding (Roche, BMS, MSD, GSK), travel/accommodation/expenses (AstraZeneca, Roche, GSK, Clovis)., (Copyright © 2023. Published by Elsevier Inc.)

Background: According to guidelines, all patients with sarcoma must be managed from initial diagnosis at expert sarcoma centers. However, in everyday practice, the time interval to an expert center visit can be long, which delays presentation to an expert multidisciplinary tumor board and increases the risk of inappropriate management, negatively affecting local tumor control and prognosis. The advent of mobile health offers an easy way to facilitate communication and cooperation between general health care providers (eg, general practitioners and radiologists) and sarcomas experts. We developed a mobile app (Sar'Connect) based on the algorithm designed by radiologists from the French Sarcoma Group. Through a small number of easy-to-answer questions, Sar'Connect provides personalized advice for the management of patients and contact information for the closest expert center., Objective: This retrospective study is the first to assess this mobile app's potential benefits in reducing the time interval for patient referral to an expert center according to the initial clinical characteristics of the soft tissue tumor., Methods: From May to December 2021, we extracted tumor mass data for 78 patients discussed by the multidisciplinary tumor boards at 3 centers of the French Sarcoma Group. We applied the Sar'Connect algorithm to these data and estimated the time interval between the first medical description of the soft tissue mass and the referral to expert center. We then compared this estimated time interval with the observed time interval., Results: We found that the use of Sar'Connect could potentially shorten the time interval to an expert center by approximately 7.5 months (P<.001). Moreover, for half (31/60, 52%) of the patients with a malignant soft tissue tumor, Sar'Connect could have avoided inappropriate management outside of the reference center. We did not identify a significant determinant for shortening the time interval for referral., Conclusions: Overall, promoting the use of a simple mobile app is an innovative and straightforward means to potentially accelerate both the referral and management of patients with soft tissue sarcoma at expert centers., (©Simon Nannini, Nicolas Penel, Emmanuelle Bompas, Thibault Willaume, Jean-Emmanuel Kurtz, Justine Gantzer. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 09.11.2022.)

Sophisticated cancer treatments, cardiovascular risk factors, and aging trigger acute cardiovascular diseases in an increasing number of cancer patients. Among acute cardiovascular diseases, cancer treatment, as well as the cancer disease itself, may induce a cardiogenic shock. Although increasing, these cardiogenic shocks are still relatively limited, and their management is a matter of debate in cancer patients. Etiologies that cause cardiogenic shock are slightly different from those of non-cancer patients, and management has some specific features always requiring a multidisciplinary approach. Recent guidelines and extensive data from the scientific literature can provide useful guidance for the management of these critical patients. Even if no etiologic therapy is available, maximal intensive supportive measures can often be justified, as most of these cardiogenic shocks are potentially reversible. In this review, we address the major etiologies that can lead to cardiogenic shock in cancer patients and discuss issues related to its management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Curtiaud, Delmas, Gantzer, Zafrani, Siegemund, Meziani and Merdji.)

Introduction: Cancer patients are at high risk of developing septic shock (SSh) and are increasingly admitted to ICU given their improved long-term prognosis. We, therefore, compared the prognosis of cancer and non-cancer patients with SSh. Methods: We conducted a monocentric, retrospective cohort study (2013−2019) on patients admitted to ICU for SSh. We compared the clinical characteristics and management and studied short- and long-term mortality with ICU and in-hospital mortality and 1-year survival according to cancer status. Results: We analyzed 239 ICU stays in 210 patients, 59.5% of whom were men (n = 125), with a median age of 66.5 (IQR 56.3−77.0). Of the 121 cancer patients (57.6% of all patients), 70 had solid tumors (33.3%), and 51 had hematological malignancies (24.3%). When comparing ICU stays of patients with versus without cancer (n = 148 vs. n = 91 stays, respectively), mortality reached 30.4% (n = 45) vs. 30.0% (n = 27) in the ICU (p = 0.95), and 41.6% (n = 59) vs. 35.6% (n = 32) in hospital (p = 0.36), respectively. ICU length of stay (LOS) was 5.0 (2.0−11.3) vs. 6.0 (3.0−15.0) days (p = 0.27), whereas in-hospital LOS was 25.5 (13.8−42.0) vs. 19.5 (10.8−41.0) days (p = 0.33). Upon multivariate analysis, renal replacement therapy (OR = 2.29, CI95%: 1.06−4.93, p = 0.03), disseminated intravascular coagulation (OR = 5.89, CI95%: 2.49−13.92, p < 0.01), and mechanical ventilation (OR = 7.85, CI95%: 2.90−21.20, p < 0.01) were associated with ICU mortality, whereas malignancy, hematological, or solid tumors were not (OR = 1.41, CI95%: 0.65−3.04; p = 0.38). Similarly, overall cancer status was not associated with in-hospital mortality (OR = 1.99, CI95%: 0.98−4.03, p = 0.06); however, solid cancers were associated with increased in-hospital mortality (OR = 2.52, CI95%: 1.12−5.67, p = 0.03). Lastly, mortality was not significantly different at 365-day follow-up between patients with and without cancer. Conclusions: In-hospital and ICU mortality, as well as LOS, were not different in SSh patients with and without cancer, suggesting that malignancies should no longer be considered a barrier to ICU admission.

Background: Thoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UT) are aggressive neoplasms. Data linking BAF alterations with tumor microenvironment (TME) and efficacy of immune checkpoint inhibitors (ICI) are contradictory. The TME of SMARCA4-UT and their response to ICI are unknown., Materials and Methods: Patients diagnosed with SMARCA4-UT in our institution were included. Immunostainings for tertiary lymphoid structures (TLS), immune cell markers, and checkpoints were assessed. Validation was performed using an independent transcriptome dataset including SMARCA4-UT, non-small cell lung cancers (NSCLC) with/without SMARCA4 mutations, and unclassified thoracic sarcomas (UTS). CXCL9 and PD-L1 expressions were assessed in NSCLC and thoracic fibroblast cell lines, with/without SMARCA4 knockdown, treated with/without interferon gamma., Results: Nine patients were identified. All samples but one showed no TLS, consistent with an immune desert TME phenotype. Four patients received ICI as part of their treatment, but the only one who responded, had a tumor with a TLS and immune-rich TME. Unsupervised clustering of the validation cohort using immune cell scores identified 2 clusters associated with cell ontogeny and immunity (cluster 1 enriched for NSCLC independently of SMARCA4 status (n = 9/10; P = .001); cluster 2 enriched for SMARCA4-UT (n = 11/12; P = .005) and UTS (n = 5/5; P = .0005). SMARCA4 loss-of-function experiments revealed interferon-induced upregulation of CXCL9 and PD-L1 expression in the NSCLC cell line with no effect on the thoracic fibroblast cell line., Conclusion: SMARCA4-UT mainly have an immune desert TME with limited efficacy to ICI. TME of SMARCA4-driven tumors varies according to the cell of origin questioning the interplay between BAF alterations, cell ontogeny and immunity., (© The Author(s) 2022. Published by Oxford University Press.)

To assess the laparoscopic interval debulking surgery (IDS) outcomes compared to laparotomy, by analyzing the overall survival (OS) and the progression free survival (PFS), as well as the intra- and post-operative morbidity., In this retrospective propensity-score-matched cohort study, all patients with stage III or IV FIGO (International Federation of Gynecology and Obstetrics) serous ovarian cancer, undergoing complete IDS after neoadjuvant chemotherapy, from January 1st of 2009 to June 1st 2019, were included., Thirty-seven patients were included in the laparoscopy group and 40 in the laparotomy group. There was no significant difference in terms of median OS between laparoscopy and laparotomy (23.1 months [95% CI 15.7-29.7] versus 26.3 months [95% CI 21.7-31.7], respectively, p  = 0.17) and median PFS (14.8 months [95% CI 10.6-21.5] versus 12 months [95% CI 11-15.1], p  = 0.057). After applying the propensity score, 25 patients were included in each group. Laparoscopy was associated with significantly less early postoperative complications (6 versus 17, p  = 0.01) and shorter hospital stay (7.6 days versus 12.1, p  < 0.001) and a significantly better OS (HR 0.45 [95% CI 0.19-0.95], p  = 0.04), but with no significant difference in terms of PFS (HR 0.71 [95% CI 0.27-1.88], p  = 0.49)., In carefully-selected patients with advanced ovarian cancer, complete laparoscopic interval debulking surgery achieves similar survival outcomes to open laparotomy. Therefore, laparoscopy appears as a safe alternative to laparotomy for IDS after NACT in selected patients with advanced ovarian cancer and a low burden of disease.

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

Desmoid tumours (DT) are rare locally infiltrative soft-tissue tumours which do not metastasise. DT arise sporadically or are associated with familial syndromes, with different clinical and genetic patterns. In recent years there has been an increasing therapeutic role of cryoablation for the treatment of sporadic DT. Therefore, in this present review, we: (a) summarize all the main epidemiological, clinical, and therapeutic aspects of sporadic DT that are relevant to an interventional radiologists' practice; (b) present the results of a systematic review that has been conducted with the intent of highlighting the main clinical outcomes available thus far with cryoablation; and (c) discuss the current and future potential applications of cryoablation in this field. Five studies were included in the systematic review accounting for 146 patients. Only 18.5% patients received cryoablation as a first-line treatment. Overall, the volume of the DT undergoing cryoablation was very large (mean total DT volume of 237 cm 3 ). Major complications were noted for 13.3-30% patients and following 2.4-6.7% interventional sessions. The rates of complete tumour response ranged between 0 and 43.3%. 1- and 3-year local progression-free survival rates were 85.1-85.8%, and 77.3-82.9%, respectively. Complete pain relief was reported in 40-66.7% symptomatic patients. In conclusion, cryoablation is currently proposed as a therapeutic strategy to very large DT, which is recognized to be associated with an increased procedure-related morbidity and reduced rates of complete tumour response. Proposing cryoablation as the first-line treatment may improve these clinical outcomes., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Ethylene glycol poisoning is relatively rare, with around a hundred cases reported each year in France. Its diagnosis is often challenging and delayed because of a several hours' free interval between ingestion of the toxic and the onset of the first symptoms. Ethylene glycol is a colorless and odorless liquid primarily found in automotive coolants, whose toxicity is linked to its hepatic metabolites. Histologically, ethylene glycol poisoning is characterized by abundant tissular deposits of calcium oxalate crystals. Under polarized light, these crystals appear birefringent and iridescent. Their microscopic appearance and their distribution are pathognomonic of oxalosis. Due to its frequent misleading presentation, the diagnosis of ethylene glycol poisoning is sometimes only made after an autopsy. Hereafter, we report the case of a 59-year-old man diagnosed with ethylene glycol intoxication after a post-mortem histopathological examination of organs., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: Borderline ovarian tumors (BOTs) are tumors with a favorable prognosis but whose management by consensus is essential to limit the risk of invasive recurrence. This study aimed to conduct an inventory of surgical practices for BOT in France and to evaluate the conformity of the treatment according to the current French guidelines., Methods: This retrospective, multicenter cohort study included nine referral centers of France between January 2001 and December 2018. It analyzed all patients with serous and mucinous BOT who had undergone surgery. A peritoneal staging in accordance with the recommendations was defined by performance of a peritoneal cytology, an omentectomy, and at least one peritoneal biopsy., Results: The study included 332 patients. A laparoscopy was performed in 79.5% of the cases. Treatment was conservative in 31.9% of the cases. The recurrence rate was significantly increased after conservative treatment (17.3% vs 3.1%; p < 0.001). Peritoneal cytology was performed for 95.5%, omentectomy for 83.1%, and at least one biopsy for 82.2% of the patients. The overall recurrence rate was 7.8%, and the recurrence was invasive in 1.2% of the cases. No link was found between the recurrence rate and the conformity of peritoneal staging. The overall rate of staging noncompliance was 22.9%., Conclusion: The current standards for BOT management seem to be well applied., (© 2021. The Author(s).)

Objectives: To describe the coinfections in invasive aspergillosis (IA), to identify factors associated with coinfections, and to evaluate the impact of coinfection on mortality., Patients and Methods: We conducted a monocentric retrospective study of consecutive putative, probable, or proven IA that occurred between 1997 and 2017. All coinfections, with an onset within 7 days before or after the first sign of aspergillosis, were identified. Factors associated with coinfections and mortality were analysed by multivariable analysis., Results: Among the 690 patients with IA included in the study, the median age was 57 years (range 7 days to 90 years). A coinfection was diagnosed in 272/690 patients (39.4%, 95%CI 35.8-43.2). The location of this coinfection was pulmonary only in 131/272 patients (48%), bloodstream only in 66/272 patients (24%) and other/multiple sites in 75/272 patients (28%). Coinfections were bacterial (110/272 patients, 40%), viral (58/272, 21%), fungal (57/272, 21%), parasitic (5/272, 2%) or due to multiple types of pathogens (42/272, 15%). Factors associated with a coinfection in adjusted analysis were: allogeneic haematopoietic stem-cell transplantation (OR 2.3 (1.2-4.4)), other haematological malignancies (OR 2.1 (1.2-3.8)), other underlying diseases (OR 4.3 (1.4-13.6)), lymphopenia (OR 1.7 (1.1-2.5)), C-reactive protein >180 mg/L (OR 1.9 (1.2-3.0)), fever (OR 2.4 (1.5-4.1)), tracheal intubation (OR 2.6 (1.5-4.7)), isolation of two or more different Aspergillus species (OR 2.7 (1.1-6.3)), and the presence of non-nodular lesions on chest computed tomography (OR 2.2 (1.3-3.7) and OR 2.2 (1.2-4.0)). Coinfections were independently associated with a higher mortality at week 12 (adjusted HR 1.5 (1.1-1.9), p < 0.01)., Conclusions: Coinfections are frequent in IA patients and are associated with higher mortality., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

PEComas is a family of rare mesenchymal tumors. This systematic review aims to better understand the natural history of advanced PEComas. After a search on the PubMed database and main oncology meeting libraries according to the PRISMA guidelines, 88 articles reported in the English literature were included. Data on clinical and histological features, treatments and outcomes were collected. To identify risk factors, univariate and multivariate analyses were performed. Seven cohorts of patients and 124 individual patients were identified. Focusing on case reports, most patients were metastatic, and the median overall survival (OS) of the entire cohort was 60 months (95%CI 33; NA). Risk factors significantly associated with OS in the multivariate analysis were the presence of metastasis at diagnosis (HR: 2.59, 95%CI 1.06; 6.33, p = 0.036) and the grouped-Bleeker's risk category (HR: 4.66; 95%CI 1.07; 20.19; p = 0.039). In the metastatic population, only the presence of lymph node metastasis was associated with OS (HR: 3.11; 95%CI 1.13; 8.60, p < 0.05). Due to a lack of events, it was not possible to conclude on other factors. This review of the literature highlights the heterogeneity of literature data and shows the great diversity of clinical management strategies.

Abstract: Succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors (GISTs) are associated with loss of function of SDH complex and represent 5% to 7.5% of GISTs. SDH-deficient GISTs usually develop in the stomach of children and young adults, and could be part of Carney triad or Carney-Stratakis syndromes including paraganglioma. SDH-deficient GISTs are often indolent despite the high rate of distant metastasis, and overall unresponsive to tyrosine kinase inhibitors. However, epigenetic inactivation of MGMT leads to potential effectiveness of alkylating agents. We report the 18F-FDG PET/CT results for monitoring response to TKI and alkylating drugs in a patient with refractory SDHB-deficient GIST., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

We describe a large series of patients with solid tumors in an early COVID-19 cluster in the eastern part of France. From February to May 2020, this multicenter retrospective study enrolled 212 patients with cancer under treatment or on follow-up for any type of malignant solid tumor and positive for SARS-CoV-2. The mortality rate was 30%. Patients with gastrointestinal cancers were identified as a subset of more vulnerable patients; immunotherapy and radiotherapy within 3 months from COVID-19 diagnosis were risk factors for death. The reported data support the essential need to be proactive and weigh the risks of morbidity from COVID-19 against the magnitude of benefits of intended cancer therapies during this pandemic. IMPLICATIONS FOR PRACTICE: This article supports the essential need to be proactive (treatment delay or modification) in oncology in the setting of pandemic. This study identified patients with gastrointestinal cancers as a more vulnerable subset of patients with cancer and found that immunotherapy and radiotherapy within 3 months from COVID-19 diagnosis to be risk factors for death. The reported data indicate the necessity of weighing the risks of morbidity from COVID-19 against the magnitude of benefits of intended cancer therapies in any future wave of COVID-19., (© 2021 AlphaMed Press.)

Epidemiological data have linked vitamin D deficiency to the onset and severity of various cancers, including prostate cancer, and although in vitro studies have demonstrated anticancer activities for vitamin D, clinical trials provided conflicting results. To determine the impact of vitamin D signaling on prostatic precancerous lesions, we treated genetically engineered Pten (i)pe-/- mice harboring prostatic intraepithelial neoplasia (PIN) with Gemini-72, a vitamin D analog with reported anticancer activities. We show that this analog induces apoptosis in senescent PINs, normalizes extracellular matrix remodeling by stromal fibroblasts, and reduces the prostatic infiltration of immunosuppressive myeloid-derived suppressor cells. Moreover, single-cell RNA-sequencing analysis demonstrates that while a subset of luminal cells expressing Krt8, Krt4, and Tacstd2 (termed luminal-C cells) is lost by such a treatment, antiapoptotic pathways are induced in persistent luminal-C cells. Therefore, our findings delineate the distinct responses of PINs and the microenvironment to Gemini-72, and shed light on mechanisms that limit treatment's efficacy., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)

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

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

Introduction: Everolimus is a mammalian target of rapamycin inhibitor and is approved as second-line treatment or beyond for renal cell carcinoma. We report a case of a 75-year-old male treated with everolimus for metastatic renal cell carcinoma, after sunitinib treatment, who was diagnosed with human herpesvirus 6 encephalitis., Case Report: After 39 months of everolimus, 10 mg per day, our patient was admitted with fever, consciousness disorders and a partial epileptic crisis. Laboratory tests revealed lymphopenia (170 lymphocytes/mm 3 ), and polymerase chain reaction in cerebrospinal fluid was positive for human herpesvirus 6. Brain magnetic resonance imaging study demonstrated hippocampal abnormality and a pontine lesion., Management and Outcome: The patient stopped everolimus treatment indefinitely. He received ganciclovir initially intravenously, with a rapid clinical improvement, as well as polyvalent immunoglobulins were given to correct hypogammaglobulinemia. Two months later, antiviral therapy was switched to oral ganciclovir, which was never stopped. A new lumbar puncture was performed one month after the initiation of antiviral treatment, which did not reveal human herpesvirus 6 DNA anymore., Discussion: Human herpesvirus 6 encephalitis is more common in hematopoietic stem cell transplant recipients and HIV patients. This is the first case probably associated to everolimus treatment. In contrast to most patients diagnosed with this infection, who either die or develop neurologic sequelae, our patient almost fully recovered two months later.