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1. Upfront surgery or definitive radiotherapy for p16+ oropharyngeal cancer. A GETTEC multicentric study

Author

Laure Santini, Agnès Dupret-Bories, Haitham Mirghani, Aicha Ben Lakdar, Pascal Roger, Guillaume Chambon, Olivier Dassonville, Françoise Chapel, Emmanuel Chamorey, Julien Viotti, Sébastien Vergez, Thibault Galissier, Karen Benezery, Valérie Coste, Benjamin Lallemant, Stéphane Temam, D. Culié, Alexandre Bozec, Nicolas Fakhry, Bruno Guelfucci, Frederic Peyrade, Anne Sophie Ramay, Anne Sudaka, Florence Jourdan-Soulier, P. Gorphe, Alain Bizeau, Gilles Poissonnet, Joanne Guerlain, Renaud Garrel, Esma Saada-Bouzid, A. Modesto, Renaud Schiappa, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Assistance Publique - Hôpitaux de Marseille (APHM), Laboratoire Parole et Langage (LPL), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Institut Gustave Roussy (IGR), Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Département de cancérologie cervico-faciale [Gustave Roussy] (CCF), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université de Montpellier (UM), Université Côte d'Azur (UCA)-UNICANCER, CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, medicine.medical_specialty, Multivariate analysis, Survival, medicine.medical_treatment, Oropharynx, Cetuximab, [SDV.CAN]Life Sciences [q-bio]/Cancer, Human papilloma virus, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, Humans, Medicine, In patient, 030223 otorhinolaryngology, Definitive radiotherapy, Cyclin-Dependent Kinase Inhibitor p16, Cancer, Aged, Neoplasm Staging, Retrospective Studies, Chemotherapy, Radiotherapy, business.industry, Papillomavirus Infections, Univariate, Chemoradiotherapy, Adjuvant, Induction Chemotherapy, General Medicine, Middle Aged, medicine.disease, 3. Good health, Surgery, Survival Rate, Radiation therapy, Oropharyngeal Neoplasms, Oncology, 030220 oncology & carcinogenesis, Propensity score matching, Female, Radiotherapy, Adjuvant, Cisplatin, Neoplasm Recurrence, Local, business
Abstract

International audience; Background: The aim of this study was to assess the impact of the initial therapeutic strategy on oncologic outcomes in patients with HPV-positive OPSCC.Methods: All p16-positive OPSCCs treated from 2009 to 2014 in 7 centers were retrospectively included and classified according to the therapeutic strategy: surgical strategy (surgery ± adjuvant radiotherapy and chemotherapy) vs. non-surgical strategy (definitive radiotherapy ± chemotherapy). Univariate, multivariate propensity score matching analyses were performed to compare overall (OS), disease-specific (DSS) and recurrence-free survival (RFS).Results: 382 patients were included (surgical group: 144; non-surgical group: 238). Five-year OS, DSS and RFS were 89.2, 96.8 and 83.9% in the surgical group and 84.2, 87.1 and 70.4% in the non-surgical group, respectively. These differences were statistically significant for DSS and RFS after multivariate analysis, but only for RFS after propensity score matching analysis.Conclusion: In p16+ OPSCC patients, upfront surgery results in higher RFS than definitive radiotherapy ± chemotherapy but does not impact OS.

Published
2021
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2. Oropharyngeal cancer: First relapse description and prognostic factor of salvage treatment according to p16 status, a GETTEC multicentric study

Author

Valérie Coste, Benjamin Lallemant, Thibault Galissier, Pascal Roger, Joanne Guerlain, Olivier Dassonville, Anne Sophie Ramay, Emmanuel Chamorey, Alain Bizeau, Anne Sudaka, Charlotte Leroy, Renaud Garrel, D. Culié, Sébastien Vergez, Stéphane Temam, Esma Saada-Bouzid, Alexandre Bozec, Quentin Lisan, Karen Benezery, Nicolas Fakhry, Florence Jourdan-Soulier, Gilles Poissonnet, Bruno Guelfucci, P. Gorphe, Frederic Peyrade, Laure Santini, Haitham Mirghani, Françoise Chapel, Guillaume Chambon, A. Modesto, Agnès Dupret-Bories, Aicha Ben Lakdar, and Renaud Schiappa

Subjects
Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Multivariate analysis, Salvage treatment, Disease, 03 medical and health sciences, Tumor Status, 0302 clinical medicine, Internal medicine, medicine, Humans, Longitudinal Studies, Cyclin-Dependent Kinase Inhibitor p16, Salvage Therapy, Human papilloma virus, Proportional hazards model, business.industry, Cancer, Middle Aged, Prognosis, medicine.disease, Oropharyngeal Neoplasms, 030104 developmental biology, 030220 oncology & carcinogenesis, Female, Observational study, Neoplasm Recurrence, Local, business
Abstract

Introduction Although Human Papilloma Virus (HPV)-driven oropharyngeal cancer (OPC) prognosis is significantly better than that of other head and neck cancers, up to 25% of cases will recur within 5 years. Data on the pattern of disease recurrence and efficiency of salvage treatment are still sparse. Material and method Observational study of all recurrent OPCs diagnosed, following a curative intent treatment, in seven French centers from 2009 to 2014. p16 Immunohistochemistry was used to determine HPV status. Clinical characteristics, distribution of recurrence site, and treatment modalities were compared by HPV tumor status. Overall survival was examined using Kaplan–Meier and multivariate Cox regression modeling. Results 350 recurrent OPC patients (246 p16-negative and 104 p16-positive patients). The site of recurrence was more frequently locoregional for p16-negative patients (65.4% versus 52.9% in p16-positive patients) and metastatic for p16-positive patients (47.1% versus 34.6% in p16-patients, p = 0.03). Time from diagnosis to recurrence did not differ between p16-positive and p16-negative patients (12 and 9.6 months, respectively, p-value = 0.2), as the main site of distant metastasis (all p-values ≥0.10). Overall and relapse-free survival following the first recurrence did not differ according to p16 status (p-values from log-rank 0.30 and 0.40, respectively). In multivariate analysis, prognosis factors for overall survival in p16-negative patients were distant metastasis (HR 2.11, 95% CI 1.30–3.43) and concurrent local and regional recurrences (HR 2.20, 95% CI 1.24–3.88). Conclusion With the exception of the initial site of recurrence, the pattern of disease relapse and the efficiency of salvage treatment are not different between p16-positive and negative OPCs.

Published
2021
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3. Genomic diversity of HPV6 and HPV11 in recurrent respiratory papillomatosis: Association with malignant transformation in the lungs and clinical outcomes

Author

Massilva Rahmoun, Audrey Aussel, Sarah Bouzidi, Vincent Pedergnana, Victor Malassigné, Julien Puech, David Veyer, Hélène Péré, Charles Lepine, Fabian Blanc, Nathalie Boulle, Valérie Costes-Martineau, and Ignacio G. Bravo

Subjects
Human papillomavirus, Recurrent respiratory papillomatosis, Squamous cell carcinoma, HPV6, HPV11, Variant, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Recurrent respiratory papillomatosis (RRP) is a rare, proliferative disease caused by human papillomavirus 6 (HPV6) and HPV11. RRP can occasionally spread and undergo malignant transformation.We analysed samples across time for five RRP patients with malignant transformation and four with highly recurrent, non-malignant RRP by applying high-throughput sequencing.Patients with malignant transformation were infected by HPV11_A1/A2, while most non-malignant cases were associated with HPV6. Transient multiple infections with HPV6 and HPV11 were found in two patients, and resolved later to single infections. Viral genome loads were homogeneous across groups (median = 78 viral genomes per human genome). Within-patient, we did not observe differences between the viral sequences in the papillomatous lesions and in the malignant tissue. Genetic analysis of the NLRP1 gene revealed no known mutations linked to idiopathic RRP, though some novel variants merit to be explored in larger cohorts.HPV11 infections appear associated with RRP malignant transformation in young patients. Multiple infections can occur in RRP, but within-patient viral diversity is minimal for a given genotype. Our results confirm the importance of viral genotype in disease prognosis and are consistent with growing evidence of HPV11 infections to be differentially associated with RRP malignant transformation in young patients.

Published
2024
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4. Synchronous primary neoplasia in patients with oropharyngeal cancer: Impact of tumor HPV status. A GETTEC multicentric study

Author

Florent Milliet, Emmanuel Chamorey, Guillaume Chambon, Laure Santini, Gilles Poissonnet, Alain Bizeau, Valérie Coste, Benjamin Lallemant, Olivier Dassonville, D. Culié, A. Modesto, Alexandre Bozec, H. Mirghani, Frederic Peyrade, Karen Benezery, Joanne Guerlain, Françoise Chapel, Thibault Galissier, Nicolas Fakhry, Agnès Dupret-Bories, Pascal Roger, Aicha Ben Lakdar, Anne Sophie Ramay, Julien Viotti, Renaud Garrel, Renaud Schiappa, Esma Saada-Bouzid, Florence Jourdan-Soulier, Stéphane Temam, Bruno Guelfucci, P. Gorphe, Anne Sudaka, Sébastien Vergez, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance Publique - Hôpitaux de Marseille (APHM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Pôle Biologie-Pathologie [CHRU Montpellier], Institut Gustave Roussy (IGR), Département de cancérologie cervico-faciale [Gustave Roussy] (CCF), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), and Salvy-Córdoba, Nathalie

Subjects
Oncology, Male, Cancer Research, MESH: Chi-Square Distribution, Multivariate analysis, Lung Neoplasms, Esophageal Neoplasms, Oropharynx, MESH: Logistic Models, Logistic regression, Neoplasms, Multiple Primary, Tertiary Care Centers, Tumor Status, 0302 clinical medicine, MESH: Neoplasms, Multiple Primary, MESH: Incidence, 030223 otorhinolaryngology, Fisher's exact test, Cancer, MESH: Human papillomavirus 16, Univariate analysis, Human papillomavirus 16, MESH: Middle Aged, Incidence, Smoking, MESH: Confidence Intervals, Middle Aged, Oropharyngeal Neoplasms, MESH: Cyclin-Dependent Kinase Inhibitor p16, 030220 oncology & carcinogenesis, MESH: Esophageal Neoplasms, symbols, Female, France, Oral Surgery, Second primary neoplasia, MESH: Smoking, medicine.medical_specialty, Alcohol Drinking, [SDV.CAN]Life Sciences [q-bio]/Cancer, Human papilloma virus, 03 medical and health sciences, symbols.namesake, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH: Analysis of Variance, Internal medicine, medicine, Confidence Intervals, MESH: Squamous Cell Carcinoma of Head and Neck, Humans, Cyclin-Dependent Kinase Inhibitor p16, Retrospective Studies, MESH: Tertiary Care Centers, Analysis of Variance, MESH: Humans, Chi-Square Distribution, business.industry, Squamous Cell Carcinoma of Head and Neck, MESH: Retrospective Studies, Retrospective cohort study, medicine.disease, Comorbidity, MESH: Male, MESH: Lung Neoplasms, MESH: France, Logistic Models, MESH: Oropharyngeal Neoplasms, business, MESH: Female, MESH: Alcohol Drinking
Abstract

International audience; Patients with oropharyngeal squamous cell carcinoma (OPSCC) display a significant risk of synchronous primary neoplasia (SPN) which could impact their management. The aims of this study were to evaluate the risk and distribution of SPN in OPSCC patients according to their HPV (p16) status, the predictive factors of SPN and the impact of SPN on therapeutic strategy and oncologic outcomes.Material and methods: All OPSCC patients treated from 2009 to 2014 were included in this multicentric retrospective study. Univariate analyses were conducted using Chi-2 and Fisher exact tests. For multivariate analyses, all variables associated with a p ≤ 0.10 in univariate analysis were included in logistic regression models.Results: Among the 1291 patients included in this study, 75 (5.8%) displayed a SPN which was preferentially located in the upper aerodigestive tract, lung and esophagus. Comorbidity level (p = 0.03), alcohol (p = 0.005) and tobacco (p = 0.01) consumptions, and p16 tumor status (p < 0.0001) were significant predictors of SPN. In multivariate analysis, p16+ status was significantly associated with a lower risk of SPN (OR = 0.251, IC95% [0.133;0.474]). Patients with a SPN were more frequently referred for non-curative treatment (p = 0.02). In patients treated with curative intent, there was no impact of SPN on the therapeutic strategy (surgical vs. non-surgical treatment). We observed no overall survival differences between patients with or without SPN.Conclusion: P16 tumor status is the main predictive factor of SPN in OPSCC patients. This study provides crucial results which should help adapt the initial work-up and the global management of OPSCC patients.

Published
2020
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5. Metachronous second primary neoplasia in oropharyngeal cancer patients: Impact of tumor HPV status. A GETTEC multicentric study

Author

Alexandre Bozec, Joanne Guerlain, Thibault Galissier, Anne Sudaka, A. Modesto, Anne Sophie Ramay, Florent Milliet, Valérie Coste, Benjamin Lallemant, Frederic Peyrade, Alain Bizeau, Renaud Garrel, Sébastien Vergez, Olivier Dassonville, Esma Saada-Bouzid, Françoise Chapel, D. Culié, Gilles Poissonnet, Emmanuel Chamorey, Karen Benezery, Pascal Roger, Aicha Ben Lakdar, Renaud Schiappa, Stéphane Temam, Laure Santini, Haitham Mirghani, Agnès Dupret-Bories, Florence Jourdan-Soulier, Guillaume Chambon, Julien Viotti, Nicolas Fakhry, Bruno Guelfucci, P. Gorphe, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance Publique - Hôpitaux de Marseille (APHM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de Radiobiologie Cellulaire et Moléculaire (IRCM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Gustave Roussy (IGR), and Département de cancérologie cervico-faciale [Gustave Roussy] (CCF)

Subjects
Oncology, MESH: Neoplasms, Second Primary, Cancer Research, medicine.medical_specialty, Multivariate analysis, Oropharynx, [SDV.CAN]Life Sciences [q-bio]/Cancer, Human papilloma virus, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, MESH: Papillomavirus Infections, MESH: Prognosis, Tumor Status, Internal medicine, medicine, MESH: Squamous Cell Carcinoma of Head and Neck, Humans, Esophagus, Cyclin-Dependent Kinase Inhibitor p16, Cancer, Retrospective Studies, MESH: Humans, Lung, Squamous Cell Carcinoma of Head and Neck, business.industry, Papillomavirus Infections, MESH: Retrospective Studies, Neoplasms, Second Primary, Retrospective cohort study, Second primary cancer, Prognosis, medicine.disease, Oropharyngeal Neoplasms, medicine.anatomical_structure, MESH: Oropharyngeal Neoplasms, MESH: Cyclin-Dependent Kinase Inhibitor p16, Immunohistochemistry, Oral Surgery, business, Second primary neoplasia
Abstract

International audience; Introduction: Patients with oropharyngeal squamous cell carcinoma (OPSCC) display a significant risk to develop a metachronous second primary neoplasia (MSPN). HPV and non-HPV-related OPSCC are 2 distinct entities with biological, clinical and prognostic differences. The aims of our study were to analyze the impact of tumor HPV status and other relevant clinical factors, such as tobacco and/or alcohol (T/A) consumption, on the risk and distribution of MSPN in OPSCC patients and to assess the impact of MSPN on patient survival.Material and methods: All OPSCC patients treated from 2009 to 2014 were included in this multicentric retrospective study. P16 immunohistochemical expression was used as a surrogate maker of tumor HPV status. The impact of tumor p16 status on the risk of MSPN was assessed in uni- and multivariate analyses. Overall survival (OS) was determined by Kaplan-Meier analysis.Results: Among the 1291 patients included in this study, 138 (10.7%) displayed a MSPN which was preferentially located in the head and neck area (H&N), lung and esophagus. Multivariate analyses showed that p16- tumor status (p = 0.003), T/A consumption (p = 0.005) and soft palate tumor site (p = 0.009) were significantly associated with a higher risk of MSPN. We found no impact of p16 tumor status on the median time between index OPSCC diagnosis and MSPN development, but a higher proportion of MSPN arising outside the H&N, lung and esophagus was found in p16 + than in p16- patients. MSPN development had an unfavorable impact (p = 0.04) on OS only in the p16 + patient group.Conclusion: P16 tumor status and T/A consumption were the main predictive factors of MSPN in OPSCC patients. This study provides crucial results with a view to tailoring global management and follow-up of OPSCC patients.

Published
2021
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6. Upfront surgery or definitive radiotherapy for patients with p16-negative oropharyngeal squamous cell carcinoma. A GETTEC multicentric study

Author

Julien Viotti, Joanne Guerlain, D. Culié, Françoise Chapel, A. Modesto, Stéphane Temam, Nicolas Fakhry, Guillaume Chambon, Laure Santini, Haitham Mirghani, Alain Bizeau, Olivier Dassonville, Anne Sophie Ramay, Frederic Peyrade, Gilles Poissonnet, Emmanuel Chamorey, Anne Sudaka, Karen Benezery, Florence Jourdan-Soulier, Renaud Schiappa, Sébastien Vergez, Alexandre Bozec, P. Gorphe, Renaud Garrel, Esma Saada-Bouzid, Agnès Dupret-Bories, Aicha Ben Lakdar, Valérie Coste, Benjamin Lallemant, Thibault Galissier, Bruno Guelfucci, and Pascal Roger

Subjects
0301 basic medicine, Male, medicine.medical_specialty, Multivariate analysis, medicine.medical_treatment, Antibodies, Viral, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Definitive radiotherapy, Retrospective Studies, Chemotherapy, Human papillomavirus 16, business.industry, Cancer, Retrospective cohort study, General Medicine, Middle Aged, medicine.disease, Prognosis, P16 Negative, Surgery, Otorhinolaryngologic Surgical Procedures, Radiation therapy, Oropharyngeal Neoplasms, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Propensity score matching, Carcinoma, Squamous Cell, Female, Radiotherapy, Adjuvant, business, Follow-Up Studies
Abstract

Introduction Therapeutic management of oropharyngeal squamous cell carcinomas (OPSCC) is still debated. Since the role of HPV was demonstrated, few studies have focused on HPV-negative OPSCC. The aim of our study was to assess the impact of therapeutic strategy (surgical vs. non-surgical) on oncologic outcomes in patients with HPV-negative OPSCC. Material and method All p16-negative OPSCCs treated from 2009 to 2014 in 7 tertiary-care centers were included in this retrospective study and were classified according to the therapeutic strategy: surgical strategy (surgery ± adjuvant radiotherapy and chemotherapy) vs. non-surgical strategy (definitive radiotherapy ± chemotherapy). Patients not eligible for surgery (unresectable tumor, poor general-health status) were excluded. Univariate, multivariate and propensity score matching analyses were performed to compare overall (OS), disease-specific (DSS) and recurrence-free survival (RFS). Results Four hundred seventy-four (474) patients were included in the study (surgical group: 196; non-surgical group: 278). Five-year OS, DSS and RFS were 76.5, 81.3 and 61.3%, respectively, in the surgical group and 49.9, 61.8 and 43.4%, respectively, in the non-surgical group. The favorable impact of primary surgical treatment on oncologic outcomes was statistically significant after multivariate analysis. This effect was more marked for locally-advanced than for early-stage tumors. Propensity score matching analysis confirmed the prognostic impact of primary surgical treatment for RFS. Conclusion Therapeutic strategy is an independent prognostic factor in patients with p16-negative OPSCC and primary surgical treatment is associated with improved OS, DSS and RFS. These results suggest that surgical strategy is a reliable option for advanced stage OPSCC.

Published
2020

7. NISCAHN: a phase II trial of nivolumab in patients with salivary gland carcinoma (Unicancer ORL-08)

Author

Christian Borel, Caroline Even, Christophe Le Tourneau, Jerome Fayette, Laurence Bozec, Joël Guigay, Sylvie Chabaud, Laurence Digue, Lionnel Geoffrois, Fréderic Rolland, Didier Cupissol, Anne Françoise Dillies, Sylvie Zanetta, Sophie Couchon-Thaunat, Valérie Costes-Martineau, Anne Sudaka-Bahadoran, Isabelle Jallut, Florence Garic, and Audrey Lardy-Cleaud

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Objective Salivary gland cancers (SGC) are rare cancers with currently no standard treatment for recurrent/metastatic disease. Based on checkpoint inhibitors benefit in a broad range of tumours, NIvolumab in Salivary gland CArcinoma of the Head and Neck (NISCAHN) evaluated nivolumab efficacy in SGC.Methods and analysis In this phase II single-stage Fleming design, patients with SGC with a progressive disease progression within 6 months prior to entering the study, were divided into ACC (adenoid cytic carcinoma) and non-ACC. All received nivolumab for a maximum of 12 months. The primary endpoint was the non-progression rate at 6 months (NPR6m) according to Response Evaluation Criteria in Solid Tumors V.1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), overall response rate (ORR), tumour growth rate, safety and quality of life (health-related quality of life).Results 46 patients with ACC and 52 patients without ACC were enrolled over 1 year. Median follow-up was respectively 29.2 months and 16.9 months for patients with ACC and non-ACC. In the ACC cohort, with 15/45 patients non-progressive at 6 months, the primary endpoint was met (33.3%; 95% CI 21.8 to NE). Nivolumab failed to demonstrate efficacy in the non-ACC cohort (NPR6m: 14.0%; 7/50 patients). ORR, PFS and OS were 8.7% (95% CI 2.4 to 20.8), 5.3 (95% CI 3.2 to 5.6) and 17.2 months (95% CI 12.5-NE) in the ACC cohort, and 3.8% (95% CI 0.5 to 13.2), 1.8 (95% CI 1.7 to 3.5) and 11.5 months (95% CI 7.5 to 14.8) in the non-ACC cohort. Nivolumab safety profile was consistent with previous reports.Conclusion Nivolumab has limited efficacy in SGC. Differential results were observed in the two cohorts. The primary endpoint was met in the ACC cohort and no new safety signals were identified.Trial registration number EudraCT number: 2016-001794-32/NCT03132038.

Published
2023
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8. A 37 mm Spindle Cell Lipoma on the Floor of the Mouth

Author

Eve Malthiery, Valérie Costes-Martineau, Marie-Alix Fauroux, and Jacques-Henri Torres

Subjects
Dentistry, RK1-715
Abstract

Spindle cell lipoma (SCL) is a rare variety of lipoma that mostly arises in male patients and rarely affects the oral cavity. The floor of the mouth is an uncommon site for SCL, and very few cases have been reported in this location. A case of SCL is reported in a 70-year-old woman who had noticed a swelling of the floor of the mouth without any functional consequence. Both ultrasonography and RMI suggested a diagnosis of ranula, whereas clinical palpation showed a nonfluctuant mass. The lesion was excised under local anesthesia. A 37×32 mm encapsulated yellow mass was removed. Histological features (mature adipocytes and CD34+ spindle cells) led to a diagnosis of SCL. Medical imaging assessment of this lesion could have been influenced by the high frequency of the ranulas in the floor of the mouth. This case appears to be quite infrequent because of its location (floor of the mouth), its size (over 3.5 cm), and the patient’s gender (female).

Published
2019
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9. Comparative Methods to Improve the Detection of BRAF V600 Mutations in Highly Pigmented Melanoma Specimens.

Author

Eric Frouin, Thierry Maudelonde, Romain Senal, Marion Larrieux, Valérie Costes, Sylvain Godreuil, Julie A Vendrell, and Jérôme Solassol

Subjects
Medicine, Science
Abstract

Genotyping BRAF in melanoma samples is often challenging. The presence of melanin greatly interferes with thermostable DNA polymerases and/or nucleic acids in traditional polymerase chain reaction (PCR)-based methods. In the present work, we evaluated three easy-to-use strategies to improve the detection of pigmented DNA refractory to PCR amplification. These pre-PCR processing methods include the addition of bovine serum albumin (BSA), the dilution of DNA, and the purification of DNA using the NucleoSpin® gDNA Clean-up XS Kit. We found that BRAF genotyping in weakly and moderately pigmented samples was more efficient when the sample was processed with BSA or purified with a NucleoSpin® gDNA Clean-up XS Kit prior to PCR amplification. In addition, the combination of both methods resulted in successful detection of BRAF mutation in pigmented specimens, including highly pigmented samples, thereby increasing the chance of patients being elicited for anti-BRAF treatment. These solutions to overcome melanin-induced PCR inhibition are of tremendous value and provide a simple solution for clinical chemistry and routine laboratory medicine.

Published
2016
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10. High CD3+ Cells in Intracranial Thrombi Represent a Biomarker of Atherothrombotic Stroke.

Author

Cyril Dargazanli, Valérie Rigau, Omer Eker, Carlos Riquelme Bareiro, Paolo Machi, Grégory Gascou, Caroline Arquizan, Xavier Ayrignac, Isabelle Mourand, Astrid Corlobé, Kyriakos Lobotesis, Nicolas Molinari, Valérie Costes, Alain Bonafé, and Vincent Costalat

Subjects
Medicine, Science
Abstract

BACKGROUND AND PURPOSE:Approximately 30% of strokes are cryptogenic despite an exhaustive in-hospital work-up. Analysis of clot composition following endovascular treatment could provide insight into stroke etiology. T-cells already have been shown to be a major component of vulnerable atherosclerotic carotid lesions. We therefore hypothesize that T-cell content in intracranial thrombi may also be a biomarker of atherothrombotic origin. MATERIALS AND METHODS:We histopathologically investigated 54 consecutive thrombi retrieved after mechanical thrombectomy in acute stroke patients. First, thrombi were classified as fibrin-dominant, erythrocyte-dominant or mixed pattern. We then performed quantitative analysis of CD3+ cells on immunohistochemically-stained thrombi and compared T-cell content between "atherothrombotic", "cardioembolism" and "other causes" stroke subtypes. RESULTS:Fourteen (26%) thrombi were defined as fibrin-dominant, 15 (28%) as erythrocyte-dominant, 25 (46%) as mixed. The stroke cause was defined as "atherothrombotic" in 10 (18.5%), "cardioembolism" in 25 (46.3%), and "other causes" in 19 (35.2%). Number of T-cells was significantly higher in thrombi from the "atherothrombotic" group (53.60 ± 28.78) than in the other causes (21.77 ± 18.31; p

Published
2016
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11. Cutaneous epithelial tumors induced by vemurafenib involve the MAPK and Pi3KCA pathways but not HPV nor HPyV viral infection.

Author

Eric Frouin, Bernard Guillot, Marion Larrieux, Ariane Tempier, Nathalie Boulle, Vincent Foulongne, Céline Girard, Valérie Costes, and Jérome Solassol

Subjects
Medicine, Science
Abstract

The inhibitors of mutant BRAF that are used to treat metastatic melanoma induce squamoproliferative lesions. We conducted a prospective histopathological and molecular study on 27 skin lesions from 12 patients treated with vemurafenib. Mutation hot spots in HRAS, NRAS, KRAS, BRAF, and Pi3KCA were screened. HPV and HPyV infection status were also determined. The lesions consisted of 19 verrucal papillomas, 1 keratoacanthoma and 7 squamous cell carcinomas. No mutations were found within BRAF and NRAS. KRAS, HRAS, and Pi3KCA oncogenic mutations were found in 10 (83.3%), 7 (58.3%), and 4 (33.3%) patients respectively; however, these mutations were not consistent within all tumors of a given patient. Pi3KCA mutation was always associated with a mutation in HRAS. Finally, no correlation was found between the mutated gene or type of mutation and the type of cutaneous tumor or clinical response to vemurafenib. P16 protein level was not indicative of HPV infection. HPV was detected in only two lesions. Two cases had MCPyV, and one had HPyV7. In conclusion, neither HPV nor HPyV seem to be involved in the development of squamoproliferative lesions induced by verumafenib. By contrast, HRAS and KRAS play a predominant role in the physiopathology of these tumors.

Published
2014
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