Variability of treatment of locally advanced cervical cancer: How French multidisciplinary teams follow European guidelines?

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.

PEC-PRO: A new prognostic score from a series of 87 patients with localized perivascular epithelioid cell neoplasms (PEComas) treated with curative intent.

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.

Characteristics, management, and outcomes of active cancer patients with cardiogenic shock.

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.

Genomic profiling of a metastatic anaplastic melanocytic neuroectodermal tumor arising from a mature thymic teratoma as part of a mediastinal germ cell tumor.

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.

SMARCB1 regulates a TFCP2L1-MYC transcriptional switch promoting renal medullary carcinoma transformation and ferroptosis resistance.

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.

Acquired L718V/TP53 co-mutation and discordant molecular pattern between plasmatic and cerebrospinal fluid in a bone and meningeal metastatic L858R+ non-small cell lung cancer: a case report.

Background: Osimertinib is approved in first line metastatic epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC). Acquired EGFR L718V mutation is a rare mechanism of resistance towards osimertinib in L858R+ NSCLC with potential sensibility to afatinib. This case reported an acquired EGFR L718V/TP53 V727M resistance co-mutation to osimertinib with discordant molecular pattern between plasmatic and cerebral fluid in a leptomeningeal and bone metastatic EGFR L858R mutant NSCLC. Case Description: A 52-year-old female, diagnosed with a bone metastatic EGFR L858R-mutated NSCLC, was treated with osimertinib as second line treatment for a leptomeningeal progression. She developed an acquired EGFR L718V/TP53 V272M resistance co-mutation after seventeen months of treatment. Discordant molecular status was observed between plasmatic (L718V+/TP53+/L858R+) and cerebrospinal fluid (CSF) (L718V-/TP53+/L858R+). Afatinib as third line did not prevent neurological progression. Conclusions: Acquired EGFR L718V mutation mediate a rare mechanism of resistance to osimertinib. Some cases reported sensibility to afatinib in patients with EGFR L718V mutation. In this described case, afatinib had no efficacy against neurological progression. This could be explained by the absence of EGFR L718V mutation in CSF tumor cells and concomitant TP53 V272M mutation as negative survival prognostic. Identify resistance mechanisms against osimertinib and develop specific therapeutic approaches remain a challenge in clinical routine.

Neoadjuvant chemotherapy with or without nintedanib for advanced epithelial ovarian cancer: Lessons from the GINECO double-blind randomized phase II CHIVA trial.

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.

Patterns of care and outcome of CIC-rearranged sarcoma patients: A nationwide study of the French sarcoma group.

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.

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

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.

Cardiogenic shock among cancer patients.

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.

Comparison of Short- and Long-Term Mortality in Patients with or without Cancer Admitted to the ICU for Septic Shock: A Retrospective Observational Study.

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.

No Geographical Inequalities in Survival for Sarcoma Patients in France: A Reference Networks' Outcome?

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.

Immune-Desert Tumor Microenvironment in Thoracic SMARCA4-Deficient Undifferentiated Tumors with Limited Efficacy of Immune Checkpoint Inhibitors.

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.

Sporadic Desmoid Tumours: Systematic Review with Reflection on the Role of Cryoablation.

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 cm3). 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.

Complete Laparoscopic Interval Debulking Surgery for Advanced Ovarian Cancer Achieves Similar Survival Outcomes to Open Approach: A Propensity-Matched Study.

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.

Natural History and Treatment Strategies of Advanced PEComas: A Systematic Review.

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.

[Histopathological diagnosis of an intoxication]. / Une intoxication de diagnostic histologique.

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.