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BackgroundUmbilical skin metastases (or Sister Mary Joseph nodules) are rare. Their presence typically indicates the late manifestation of deep-seated abdominopelvic malignancy. They occur mainly in gynecological cancers, and gastro-intestinal cancers in men. The most common histology is adenocarcinoma (~ 75% of cases), but it can also rarely be squamous cell or undifferentiated carcinoma. These metastases can be present at diagnosis or appear at disease recurrence, and are associated with a very poor prognosis with an average survival of 11 months.Case presentationWe report the clinical case of a 58-year-old man with metastatic pancreatic adenocarcinoma and umbilical cutaneous metastasis after receiving first-line chemotherapy. The diagnosis was established upon liver biopsy in July 2019, after the patient presented with complaint of transfixiant abdominal pain. The first-line treatment consisted of six cycles of modified FOLFIRINOX chemotherapy. However, in November 2019, computed tomography (CT) scan showed disease progression. Second-line treatment with gemcitabine (brand name: Gemzar) led to a 16% decrease of target lesions. During the fourth cycle, three periumbilical indurated nodules appeared. After six cycles, skin infiltration had increased and the patient reported his abdominal pain had intensified. Reassessment by CT scan showed an increase in both hepatic and peritoneal disease progression. Third-line treatment with FOLFIRI, started on April 15, 2020, was not able to control the disease, leading to greater induration and subcutaneous infiltration, which were responsible for the increased pain and ultimate death.ConclusionUmbilical skin metastases are rare and they are associated with advanced metastatic disease and a very poor prognosis. Cases reporting Sister Mary Joseph nodules are needed to better understand the conditions and mechanisms of their appearance and dissemination.

International audience; Background To assess the impact of nutritional status on tolerance to induction chemotherapy by docetaxel, cisplatin and 5-fluorouracil (ICT) in head and neck cancer (HNC). Methods Ninety-two HNC patients were included. Toxicity was assessed according to common terminology criteria for adverse events. Nutritional status was assessed by body mass index (BMI), serum albumin, nutritional risk index (NRI), and CT scan (skeletal muscle mass index [SMI] at the first lumbar vertebral level). Results Before treatment, average BMI was 22.7 +/- 4.6 kg/m(2), serum albumin 38.7 +/- 5.8 g/L, NRI 97.6 +/- 10.6, and SMI 36.4 +/- 7.9 cm(2)/m(2). After treatment, BMI was 23 +/- 4.5, serum albumin 30.2 +/- 7.1, and NRI 88.1 +/- 9.2. During ICT, 52 (62%) patients developed at least one toxicity >= Grade 3. Pre-treatment SMI was the only predictive factor of toxicity irrespective of BMI (p = 0.04). Conclusion Low skeletal muscle mass is a predictive factor of toxicity to ICT in HNC.

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

International audience; Objectives To determine the importance of nutritional status, social status, and inflammatory status in the prognosis of head and neck cancer. Study Design Single-center retrospective study of prospectively collected data. Setting Tertiary referral center. Methods Ninety-two consecutive patients newly diagnosed for cancer of the upper aerodigestive tract without metastases were assessed at time of diagnosis for several prognostic factors. Nutritional status was assessed by the nutritional risk index, social status by the EPICES score, and inflammatory status by the systemic inflammatory response index. The primary endpoint was overall survival. Results In multivariable analysis, the main prognostic factors were the TNM classification (hazard ratio [HR] = 3.34, P = .002, for stage T3-4), malnutrition as assessed by the nutritional risk index (HR = 3.64, P = .008, for severe malnutrition), and a systemic inflammatory response index score ≥1.6 (HR = 3.32, P = .02). Social deprivation was not a prognostic factor. Conclusion Prognosis in head and neck cancer is multifactorial; however, malnutrition and inflammation are important factors that are potentially reversible by early intervention.; Tertiary referral center.

BackgroundThe rate of toxic deaths related to induction chemotherapy in the treatment of locally advanced head and neck cancers is unacceptable and calls into question this therapeutic strategy, which is however highly effective in terms of rate and speed of response. The purpose of the study was to investigate predictive factors of toxicity of induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (TPF) in locally advanced head and neck cancers (LAHNC).MethodsBetween June 2009 and December 2017, 113 patients treated consecutively with TPF were included retrospectively. Patients were receiving induction chemotherapy for either an inoperable cancer or laryngeal preservation. For inoperable cancer, induction chemotherapy was proposed to patients presenting either a large tumor with strong symptoms (dyspnea, dysphagia, pain) or a tumor with rapid progression. Risk factors were chosen among the initial patient and tumour characteristics and chemotherapy modalities.ResultsEighty-nine patients (79%) were male; the median age was 58 years [32–71]. Sixty-nine (61%) patients were treated for inoperable cancer and 44 (39%) for laryngeal preservation. 45% had stage IVa cancer, 28% stage III and 25% stage IVb. Sixty percent of patients had a partial response after TPF, 22% had a complete response, 12% were stable, 5% were progressing, and 1% had a discordant response. Thirty-four patients (30%) received enteral feeding during induction chemotherapy with TPF. The possibility of oral feeding without a tube was predictive of a better response (p = 0.003). Seven (6%) patients died during TPF. There was an increased risk of death with preexisting liver dysfunction (liver dysmorphia on imaging or decrease prothrombin rate) (p = 0.032). There was an increased risk of grade ≥ 3 infection if an enteral feeding occurred during the period of induction chemotherapy (p = 0.03).ConclusionsTPF induction chemotherapy had an 82% objective response rate with 6% toxic deaths. Nutritional status and the presence of hepatic dysfunction are significant risk factors to be taken into account in therapeutic decisions.

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.

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.

International audience; Background: Meningeal melanocytoma (MM) is a locally aggressive, low-grade primary melanocytic tumor of the central nervous system (PMN-CNS). According to the literature, GNAQ and GNA11 mutations are relatively frequent. In contrast, BRAF and NRAS mutations are very rare. Other series have reported BAP1 mutation, monosomy 3 and gain of chromosome 6. In this paper, we discussed two cases of MM for whom a FoundationOne CDxTM assay was performed.Results: Case report 1: A 48 year old man was diagnosed with intermediate-grade MM based on histological assessment, which is consistent with the clinical evolution. The FoundationOne CDxTM assay detected a SF3B1 mutation, usually found in 15% of uveal melanomas. This mutation is correlated with improved progression-free survival in uveal melanomas. Case report 2: A 39 year old women was diagnosed with MM. Her evolution wasn’t expected based on histology only; her history didn’t match with rather benign histological features microscopically. The FoundationOne CDxTM assay provided two interesting elements: first, the tumour was positive for CDKN2A p16INK4a M52fs*1 and p14ARF H66fs*106 mutations, most commonly found in cutaneous melanomas. Secondly, a GNA11 Q209L mutation, known to be a marker of aggressiveness in uveal melanoma, was detected.Conclusion: The identification of molecular alterations in PMN-CNS, in addition to immunohistochemical analysis could provide a better understanding of the biological and clinical behaviour of these tumours, a better identification of melanocytic melanomas with poor prognosis and a high risk of relapse or metastasis, and the development of novel therapeutic options for these patients.

Resume Objectif de l’etude L’objectif de l’etude etait de rechercher des facteurs predictifs de toxicite de la chimiotherapie d’induction par l'association de docetaxel, platine et 5-fluorouracile (TPF) pour les cancers localement evolues des voies aerodigestives superieures. Patients et methodes De juillet 2009 a mars 2015, 57 patients pris en charge consecutivement par TPF ont ete inclus retrospectivement. Quarante-sept patients (83 %) etaient des hommes ; l’âge median etait de 56 ans [40–71 ans]. Trente-huit patients (67 %) etaient pris en charge pour un cancer inoperable (tres symptomatique et/ou forte charge tumorale) et 19 (33 %) en preservation laryngee. Il y avait 47 % cancers de stade IVa, 32 % de stade III et 21 % de stade IVb. Au moment du diagnostic, il y avait 53 % de poids stables, 28 % d’amaigrissements de grade 1, 17 % de grade 2 et 2 % de grade 3. Resultats Quarante-sept pour cent des patients etaient en situation de reponse partielle apres la chimiotherapie par TPF, 28 % de reponse complete, 7 % de stabilite, 2 % de progression et 2 % de reponse discordante. La possibilite d’alimentation orale sans sonde etait predictive d’une meilleure reponse (p = 0,02). Trente-neuf pour cent des patients ont pris du poids pendant le traitement, 35 % etaient stables et 26 % en perte de poids. Six patients (10,5 %) sont decedes au cours du traitement, quatre de neutropenie febrile, un de pneumopathie et un de cause inconnue. L’âge de plus de 57 ans etait associe a un risque plus eleve d’anemie et de thrombopenie de grade ≥ 3. Il existait un risque plus important d’infection de grade ≥ 3 en cas de perte de poids au moment du diagnostic (p = 0,035) et d’alimentation enterale (p = 0,05). Il existait un risque plus important de neutropenie de grade ≥ 3 en cas de perte de poids pendant la chimiotherapie (p = 0,03). Conclusion La chimiotherapie d’induction par TPF presente une efficacite antitumorale importante (75 % de reponse objective) mais une forte morbidite avec 10,5 % de deces iatrogeniques dans notre population tres symptomatique avec une charge tumorale tres importante. Le statut nutritionnel est un facteur important a prendre en compte dans la decision therapeutique.

6516 Background: Monalizumab is a first-in-class immune checkpoint inhibitor targeting Natural Killer Group 2A (NKG2A), which is expressed on subsets of Natural Killer (NK), gd T and tumor-infiltrating CD8+T cells. NKG2A blockade promotes innate anti-tumor immunity mediated by NK and CD8+T cells and enhances NK cell antibody-dependent cell-mediated cytotoxicity induced by cetuximab. In a Phase I study, the combination of monalizumab and cetuximab was well tolerated. In an initial expansion cohort 1 of 40 patients (pts) who had progressed after platinum-based therapy, we reported an overall response rate (ORR) of 27.5%, a 4.5 month median PFS and an 8.5 month median OS. In a subset of patients (n=18) previously treated with PD-(L)1 inhibitors (IO), corresponding results were 17%, 5.1, and 14.1 months, respectively (ESMO 2019). Here we present data from a second expansion cohort 2 (n=40) conducted specifically in the post-IO setting to independently confirm the cohort 1 results. Methods: Eligible patients had R/M SCCHN previously treated with platinum and a PD-(L)1 inhibitor. Pts received monalizumab 750 mg q2weeks and cetuximab according to the label until progression or toxicity. Cohort 2 was designed as a confirmatory multicenter single arm phase II study, with a pre-planned total of 40 patients. The primary endpoint was ORR assessed per RECIST 1.1. Results: As of January 31, 2020, 40 pts have been treated in cohort 2. Median follow-up is 7.3 months (range, 1.9-13.6+). Eight (8) pts have a confirmed partial response (PR); ORR is 20% [95% confidence interval: 11-35]. Median time to response is 1.6 months [1.6-5.3]. At the time of data analysis, 3 pts were still in PR and 3 pts had stable disease continue on treatment. PFS and OS are still immature. Conclusions: In pts previously treated with platinum and PD-(L)1 inhibitors, the combination of monalizumab and cetuximab demonstrated promising activity. The second extension cohort confirmed prospectively the ORR reported in cohort 1. A randomized phase III trial of monalizumab and cetuximab is planned in this platinum and IO-pretreated SCCHN population. Clinical trial information: NCT02643550 .

Contexte : Plus de 80% des patients recevant du nivolumab en 2ème ligne de traitement dans les carcinomes épidermoïdes de la tête et du cou (CETEC) récidivants et/ou métastatiques n’obtiendront aucun bénéfice au traitement, sans qu’il soit possible de les identifier.Objectif principal : Déterminer la corrélation entre les variations des paramètres sanguins tels que le rapport neutrophiles sur lymphocytes (NLR), plaquettes sur lymphocytes (PLR), lymphocytes sur globules blancs totaux (LWR) et la réponse au nivolumab dans les CETEC.Matériels et Méthodes : Nous avons analysé rétrospectivement les données biologiques de 44 patients atteints de CETEC ayant reçu du nivolumab et au moins une ligne antérieure de traitement systémique au Centre Jean Perrin, France de mars 2018 à décembre 2020.Résultats : Le taux de réponses objectives était de 15.9%. Un NLR bas à 2 cycles de nivolumab était associé à une meilleure réponse [OR=0.897, p=0.013]. La médiane de survie globale (SG) était de 17 mois (CI95% 14-28). Une augmentation du LWR du 6ème au 8ème cycle de nivolumab était associée à une meilleure survie globale [HR = 0.091, p = 0.005]. La médiane de survie sans progression (SSP) était de 3 mois.L’augmentation du PLR entre la valeur initiale et le 6ème cycle de nivolumab était associée à une diminution de la SSP [HR = 1.752, p = 0.039]. Les patients ayant un NLR ≤ 5 et PLR ≤ 150 avaient une médiane de délai avant arrêt du traitement (TTF) augmentée de 1 à 3 mois (p = 0.012) et de 3 à 5 mois (p = 0.027) par rapport aux patients ayant un NLR > 5 et PLR > 150 respectivement. L’augmentation du LWR du 6èmeau 8ème cycle était significativement associée à une augmentation du TTF [HR = 0.050, p = 0.001].Conclusion: Une augmentation du taux de variation du LWR et une faible valeur de NLR en cours de traitement par nivolumab sont associées à une augmentation de la SG et du TTF. Une augmentation du PLR et du NLR sont des facteurs de mauvais pronostics. L’augmentation du nombre de lymphocytes sous immunothérapie semble être un bon marqueur d’efficacité du traitement dans les CETEC.