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High-grade epithelial ovarian cancer (HGEOC) is a heterogeneous disease and among the deadliest types of cancer. It often acquires resistance to conventional chemotherapy and its prognosis remains highly poor. The tissue protein nestin, implicated in the assembly and disassembly of intermediate filaments, has been reported to be an unfavourable prognostic factor in several cancer types. We hypothesized that HGEOC progression is regulated by the proliferation of chemoresistant cancer stem cells, in which nestin might be implicated. This preliminary study aimed to evaluate nestin as a prognostic biomarker in HGEOC treated by neoadjuvant chemotherapy (NACT) followed by cytoreductive surgery.A retrospective study (2009-2019) was conducted on 92 patients with primary ovarian, fallopian tube or peritoneal HGEOC who underwent NACT followed by cytoreductive surgery. Nestin expression in tissue samples was semi-quantitatively evaluated defining nestin positivity for those with histochemical score ≥30. We then evaluated the prognostic value of nestin expression.The median progression-free survival was similar between nestin-positive (22 months) and nestin-negative (19 months) groups (p=0.57). Interestingly, the median overall survival was shorter for the nestin-positive group (48 vs. 67 months, respectively), however the difference did not reach statistical significance (p=0.43).Tissue nestin expression does not appear to be a relevant prognostic biomarker in HGEOC treated by NACT. However, we believe that prospective studies in larger cohorts should be conducted and evaluation of nestin in pre-NACT HGEOC samples needs to be explored.

Brice Leyrat,1,2 Xavier Durando,1– 5 Hugo Veyssiere,3– 5 Maureen Bernadach1,3– 5 1Département d’Oncologie Médicale, Centre Jean Perrin, Clermont-Ferrand, 63011, France; 2Université Clermont Auvergne, UFR Médecine, Clermont-Ferrand, 63000, France; 3Université Clermont Auvergne, INSERM, U1240 Imagerie Moléculaire et Stratégies Théranostiques, Centre Jean Perrin, Clermont-Ferrand, 63011, France; 4Division de Recherche Clinique, Délégation Recherche Clinique et Innovation, Centre de Lutte contre le Cancer, Centre Jean Perrin, Clermont-Ferrand Cedex 1, 63011, France; 5Centre d’Investigation Clinique, UMR501, Clermont-Ferrand, 63011, FranceCorrespondence: Hugo VeyssiereDivision de Recherche Clinique, Centre de Lutte contre le Cancer, Centre Jean Perrin, 58, Rue Montalembert, Clermont-Ferrand, 63011, FranceEmail Hugo.VEYSSIERE@clermont.unicancer.frBackground: For patients with non-epidermal non–small-cell lung cancer (NSCLC), molecular alterations should always be investigated, especially in non-smokers, who have a very high frequency of targetable alterations (EGFR 52%; ALK 8% in particular). MET exon 14 alterations are identified in 3– 4% of NSCLCs and MET gene amplification and high protein expression are associated with a poor prognosis. The French recommendations only authorize the use of capmatinib and crizotinib if the mutation concerns exon 14. However, several different types of mutation in exon 14 of MET and its flanking introns can induce a jump in exon 14, activate the MET gene and thus be sensitive to anti-MET tyrosine kinase inhibitors.Case Summary: This case concerns a 76-year-old Caucasian male with a medical history including idiopathic thrombocytopenic purpura, chronic myelomonocytic leukemia (CMML), atrial fibrillation, arterial hypertension, obesity (BMI 36kg/m2), and a 5– 10 pack-per-year smoking history. A left upper lobe pulmonary nodule of 12.4 mm was discovered in March 2019. The patient received adjuvant chemotherapy with carboplatin AUC 5 and vinorelbine 25.00 mg/m2. At the end of the adjuvant treatment, the patient was in complete remission for 5 months. In February 2020, the CT scan revealed a mediastinal lymph node progression. A complementary molecular analysis was realized on the initial surgical specimen. A c.3082+3A>T mutation in the MET gene was identified. This mutation confers susceptibility to anti-MET tyrosine kinase inhibitors. Treatment with crizotinib was initiated with an initial dose of 250 mg/day for 15 days and then increased to 250 mg twice a day. After 7 months of treatment with crizotinib, the disease was still stable according to RECIST 1.1.Conclusion: We report here the original case of a patient presenting a lung adenocarcinoma with an intron 14 mutation and having a durable TKI response.Keywords: crizotinib, next-generation sequencing, MET intron 14 mutation, non-small-cell lung cancer

BACKGROUND Thymic epithelial carcinomas are rare and have a poor prognosis. Treatment of thymic epithelial carcinoma is multimodal and includes surgery, post-operative radiation therapy, adjuvant and neoadjuvant chemotherapy, or exclusive chemotherapy based on disease resectability. However, there is currently no standard treatment regimen for metastatic and recurrent thymic carcinoma. CASE SUMMARY A 45-year-old Caucasian male, with no past medical history, presented with hepatalgia and a cervical mass. A computed tomography (CT) scan showed multiple suspect lesions in the lungs, liver, and anterior mediastinum associated with mediastinal and cervical adenopathy. CT-guided percutaneous biopsies of the liver lesions and anterior mediastinal mass were performed, confirming the histopathology of thymic epithelial carcinoma. Management consisted of several chemotherapy regimens and radiation therapy, administered between April 2016 and December 2018. The patient achieved complete metabolic response. Fluorodeoxyglucose positron emission tomography/CT performed in June 2019 showed disease relapse, with reappearance of a large hypermetabolic hepatic mass and involvement of mediastinal and axillary lymph nodes. Intravenous pembrolizumab (200 mg, every 3 wk) was administered after two prior systemic therapies. The patient’s response to treatment was last documented on March 5, 2020. CONCLUSION Pembrolizumab was successful in treatment of a patient with programmed death-ligand 1-negative metastatic thymic carcinoma, pretreated with chemotherapy.

International audience; Purpose: The purpose of this study was to create an algorithm to detect and classify pulmonary nodules in two categories based on their volume greater than 100 mm3 or not, using machine learning and deep learning techniques.Materials and method: The dataset used to train the model was provided by the organization team of the SFR (French Radiological Society) Data Challenge 2019. An asynchronous and parallel 3-stages pipeline was developed to process all the data (a data "pre-processing" stage; a "nodule detection" stage; a "classifier" stage). Lung segmentation was achieved using 3D U-NET algorithm; nodule detection was done using 3D Retina-UNET and classifier stage with a support vector machine algorithm on selected features. Performances were assessed using area under receiver operating characteristics curve (AUROC).Results: The pipeline showed good performance for pathological nodule detection and patient diagnosis. With the preparation dataset, an AUROC of 0.9058 (95% confidence interval [CI]: 0.8746-0.9362) was obtained, 87% yielding accuracy (95% CI: 84.83%-91.03%) for the "nodule detection" stage, corresponding to 86% specificity (95% CI: 82%-92%) and 89% sensitivity (95% CI: 84.83%-91.03%).Conclusion: A fully functional pipeline using 3D U-NET, 3D Retina-UNET and classifier stage with a support vector machine algorithm was developed, resulting in high capabilities for pulmonary nodule classification.

Background Triple negative breast cancer affects 10% to 20% of all women diagnosed with breast cancer. Due to its characteristics, treatment strategies are limited and metastatic recurrences are common in the first 5 years after treatment. However, not all patients affected by this disease develop metastases. Tumor-infiltrating lymphocytes have shown to be reliable predictive biomarkers of treatment response and metastatic recurrences. However, we need to develop simpler and faster ways to predict response to cytotoxic treatment and the possibility of eventual cancer relapse by identifying new biomarkers. Recently, new studies are emerging, suggesting a predictive role of circulating blood cells in different types of cancer. In this study, we will assess the correlation between tumor-infiltrating lymphocytes and different elements of the blood count in patients diagnosed with triple negative breast cancer. Methods The main objective of this study is to evaluate the correlation between the peripheral neutrophil-to-lymphocyte ratio and the amount of tumor-infiltrating lymphocytes, assessed in triple negative breast cancer patients at diagnosis. Secondary objectives include evaluation of the correlation between tumor-infiltrating lymphocytes at diagnosis and the baseline absolute neutrophil, lymphocyte, and platelet counts, as well as the platelet-to-lymphocyte ratio. The triple negative breast cancer patients will be enrolled in the PERCEPTION trial during the first year after the treatment completion. Two supplementary blood tests, at 12 months after the end of treatment and at the time of the first metastatic recurrence, will be performed. Discussion The discovery of new prognostic and predictive biomarkers is crucial for triple negative breast cancer. We set up the PERCEPTION clinical trial in order to evaluate certain blood counts as early biomarkers and to assess their correlation with tumor-infiltrating lymphocytes. Demonstration of comparative predictive and/or prognostic capacities of peripheral blood counts and tumor-infiltrating lymphocytes would allow introduction of the former as simple and cheap biomarkers in triple negative breast cancer patient management. Trial registration The PERCEPTION study has been registered in the French National Agency of Medical Security registry on the 2nd of July 2019 under the number 2019-A01861-56 and in the ClinicalTrials.org registry under the number NCT04068623.