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1.
Eur Arch Otorhinolaryngol ; 279(7): 3629-3637, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35076745

RESUMO

INTRODUCTION: Hypopharyngeal cancer (HC) is an aggressive and life-threatening malignancy that requires a complex multimodal treatment. The aims of the present study were to analyze, in locally advanced HC patients, the oncologic and swallowing outcomes and their predictive factors according to the therapeutic strategy. METHODS: All patients with locally advanced HC (T3/T4, N0-3, M0) treated at our institution between 2000 and 2020 were included in this retrospective study. Patients were classified in 3 groups according to the therapeutic strategy: primary radical surgery (RS), induction chemotherapy (ICT) or definitive (chemo)-radiation therapy ((C)RT). Predictive factors of oncologic outcomes (overall, cause-specific and recurrence-free survival: OS, CSS and RFS) and swallowing outcome (dysphagia outcome and severity scale: DOSS) were investigated in univariate and multivariate analysis. RESULTS: A total of 217 patients were included in this study (RS: 40; ICT: 106; (C)RT: 71). 5-year OS, CSS and RFS rates were 36, 38 and 32%, respectively. ICT was associated with improved oncologic and swallowing outcomes in univariate analysis. After multivariate analysis, patient age ≥ 70 years (p = 0.0002) was the only factor significantly associated with a worse OS, whereas patient age ≥ 70 years (p = 0.002) and N stage ≥ 2 (p = 0.01) were significantly associated with a worse CSS. Comorbidity level (KFI ≥ 2; p = 0.01) and N stage (≥ 2; p = 0.02) were significantly associated with worse swallowing outcomes. CONCLUSION: In selected locally advanced HC patients, an ICT-based therapeutic strategy offers acceptable oncologic and functional outcomes. Patient age, N stage and comorbidity level are the main determinants of oncologic and functional outcomes.


Assuntos
Neoplasias Hipofaríngeas , Idoso , Terapia Combinada , Deglutição , Humanos , Neoplasias Hipofaríngeas/patologia , Neoplasias Hipofaríngeas/terapia , Quimioterapia de Indução , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento
3.
Eur Arch Otorhinolaryngol ; 274(1): 441-449, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27438536

RESUMO

The aims of this study were to evaluate clinical outcomes and to determine their predictive factors in patients with oral cavity squamous cell carcinoma (OCSCC) invading the mandibular bone (T4) who underwent primary radical surgery and fibula free-flap reconstruction. Between 2001 and 2013, all patients who underwent primary surgery and mandibular fibula free-flap reconstruction for OCSCC were enrolled in this retrospective study. Predictive factors of oncologic and functional outcomes were assessed in univariate and multivariate analysis. 77 patients (55 men and 22 women, mean age 62 ± 10.6 years) were enrolled in this study. Free-flap failure and local and general complication rates were 9, 31, and 22 %, respectively. In multivariate analysis, ASA score (p = 0.002), pathologic N-stage (p = 0.01), and close surgical margins (p = 0.03) were independent predictors of overall survival. Six months after therapy, oral diet, speech intelligibility, and mouth opening functions were normal or slightly impaired in, respectively, 79, 88, and 83 % of patients. 6.5 % of patients remaining dependent on enteral nutrition 6 months after therapy. With acceptable postoperative outcomes and satisfactory oncologic and functional results, segmental mandibulectomy with fibula free-flap reconstruction should be considered the gold standard primary treatment for patients with OCSCC invading mandible bone. Oncologic outcomes are dependent on three main factors: ASA score, pathologic N-stage, and surgical margin status.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Fíbula/transplante , Retalhos de Tecido Biológico , Mandíbula/cirurgia , Neoplasias Bucais/cirurgia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Mandíbula/patologia , Margens de Excisão , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Análise Multivariada , Invasividade Neoplásica , Estadiamento de Neoplasias , Procedimentos de Cirurgia Plástica , Estudos Retrospectivos
4.
Eur Arch Otorhinolaryngol ; 273(10): 3299-306, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26858198

RESUMO

To evaluate oncologic and functional outcomes and prognostic factors in patients with locally advanced hypopharyngeal cancer included in an induction chemotherapy (ICT)-based larynx preservation program in daily clinical practice. All patients with locally advanced (T3/4, N0-3, M0) hypopharyngeal squamous cell carcinoma, technically suitable for total pharyngo-laryngectomy, treated by docetaxel (75 mg/m(2), day 1), cisplatin (75 mg/m(2), day 1) and 5-fluorouracil (750 mg/m(2)/day, day 1-5) (TPF)-ICT (2-3 cycles) for larynx preservation at our institution between 2004 and 2013, were included in this retrospective study. Prognostic factors of oncologic (overall, cause-specific and recurrence-free survival: OS, SS and RFS) and functional (dysphagia outcome and severity scale, permanent enteral nutrition, larynx preservation) outcomes were assessed in univariate and multivariate analyses. A total of 53 patients (42 men and 11 women, mean age 58.6 ± 8.2 years) were included in this study. Grade 3-4 toxicities were experienced by 17 (32 %) patients during ICT. The rate of poor response (response <50 % without larynx remobilization) to ICT was 10 %. At 5 years, OS, SS and RFS rates were 56, 60 and 54 %, respectively. Four patients required definitive enteral nutrition (permanent enteral tube feeding). The rate of patients alive, disease-free and with a functional larynx at 2 years was 58 %. T4 tumor stage (p = 0.005) and response to ICT <50 % (p = 0.02) were independent prognostic factors of OS. Response to ICT was significantly associated with the risk of permanent enteral nutrition (p = 0.04) and larynx preservation (p = 0.01). In daily clinical practice, a TPF-ICT-based larynx preservation protocol can be used in patients with locally advanced hypopharyngeal cancer with satisfactory results in terms of tolerance, efficacy and oncologic and functional outcomes.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Laríngeas , Laringectomia/métodos , Complicações Pós-Operatórias , Idoso , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Cisplatino/administração & dosagem , Terapia Combinada , Feminino , Fluoruracila/administração & dosagem , França , Humanos , Quimioterapia de Indução/métodos , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/terapia , Laringe/patologia , Laringe/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Tratamentos com Preservação do Órgão/métodos , Avaliação de Processos e Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/fisiopatologia , Prognóstico , Estudos Retrospectivos , Taxoides/administração & dosagem
5.
Eur Arch Otorhinolaryngol ; 273(9): 2681-7, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26395117

RESUMO

The objective of the study is to evaluate the nutritional status and determine its impact on clinical outcomes in patients with locally advanced hypopharyngeal cancer included in an induction chemotherapy (ICT)-based larynx preservation program without prophylactic feeding-tube placement. All patients with locally advanced (T3/4, N0-3, M0) hypopharyngeal squamous cell carcinoma, technically suitable for total pharyngolaryngectomy, treated by docetaxel, cisplatin and 5-fluorouracil (TPF)-ICT for larynx preservation at our institution between 2004 and 2013, were included in this retrospective study. Patients' nutritional status was closely monitored. Enteral nutrition was used if and when a patient was unable to sustain per-oral nutrition and hydration. The impact of nutritional status on clinical outcomes was investigated in univariate and multivariate analysis. A total of 53 patients (42 men and 11 women, mean age = 58.6 ± 8.2 years) were included in this study. Six (11.3 %) patients had lost more than 10 % of their usual body weight before therapy. Compared with patients' usual weight, the mean maximum patient weight loss during therapeutic management was 8.7 ± 4.5 kg. Enteral nutrition was required in 17 patients (32 %). We found no influence of the tested nutritional status-related factors on response to ICT, toxicity of ICT, overall, cause-specific and recurrence-free survival, and on post-therapeutic swallowing outcome. Maximum weight loss was significantly associated with a higher risk of enteral tube feeding during therapy (p = 0.03) and of complications (grade ≥3, p = 0.006) during RT. Without prophylactic feeding-tube placement, approximately one-third of the patients required enteral nutrition. There was no significant impact of nutritional status on oncologic or functional outcomes.


Assuntos
Carcinoma de Células Escamosas/terapia , Nutrição Enteral , Neoplasias Hipofaríngeas/terapia , Quimioterapia de Indução , Intubação Gastrointestinal , Estado Nutricional , Tratamentos com Preservação do Órgão , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Cisplatino/uso terapêutico , Docetaxel , Feminino , Fluoruracila/uso terapêutico , Humanos , Neoplasias Hipofaríngeas/mortalidade , Neoplasias Hipofaríngeas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxoides/uso terapêutico
6.
Eur Arch Otorhinolaryngol ; 271(4): 801-7, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23771320

RESUMO

The aims of this study were to evaluate long-term quality of life (QoL) and to determine its predictive factors after oncologic surgery and free flap reconstruction in patients with oral or oropharyngeal cancer. Patients treated at our institution between 2000 and 2009, who are alive and disease-free at least 1 year after therapy, completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire and the specific H&N35 module. Eighty patients were included in our study. Global QoL score was 69.3 ± 22.7%. Global QoL and general symptoms were correlated with T stage, whereas head and neck symptoms were correlated with T stage and tumor involvement of the tongue base. Emotional and social functioning scales, and resumption of professional activity were significantly associated with global QoL. In conclusion, T stage, tumor involvement of the tongue base, professional status and emotional and social functions were the main determinants of QoL in our study.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Microvasos/cirurgia , Neoplasias Bucais/cirurgia , Neoplasias Orofaríngeas/cirurgia , Qualidade de Vida , Retalhos Cirúrgicos , Idoso , Carcinoma de Células Escamosas/psicologia , Fadiga , Comportamento Alimentar , Feminino , Neoplasias de Cabeça e Pescoço/psicologia , Humanos , Masculino , Neoplasias Bucais/psicologia , Análise Multivariada , Neoplasias Orofaríngeas/psicologia , Qualidade de Vida/psicologia , Procedimentos de Cirurgia Plástica , Participação Social , Carcinoma de Células Escamosas de Cabeça e Pescoço , Inquéritos e Questionários , Resultado do Tratamento
7.
Invest New Drugs ; 31(1): 59-65, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22714791

RESUMO

BACKGROUND: Radiotherapy (RT) is the standard treatment for uveal melanoma. However it can cause damage to the retina and optic nerve. This study examined the in vitro and in vivo effects of the anti-VEGF monoclonal antibody bevacizumab associated with radiotherapy (RT) on tumor growth and tumor proliferation and vasculature on OCM-1 human uveal melanoma cell line. METHODS: The anti-proliferative effects of bevacizumab, RT and their combination were tested both in vitro (OCM-1 cells co-cultured with HUVEC cells in Transwell plates) and in vivo (OCM-1 tumor xenografts in nude mice). In addition, treatment effects in vitro on VEGF secretion, as well as treatment effects in vivo on tumor proliferation (Ki67 labelling), tumor vasculature (VEGFR2 labelling) and VEGF tumoral concentration were analyzed. RESULTS: Bevacizumab given alone had a significant impact on tumor growth in vivo (and moderate effects in vitro). The bevacizumab-RT combination had additive effects in vitro (tumor cell proliferation) and in vivo (tumor growth), which translated into a significant decrease in Ki67 expression, VEGFR2 labelling and VEGF tumoral content. CONCLUSIONS: The bevacizumab-RT combination could be a promising clinical option to explore for the management of human uveal melanoma, since it may allow RT dose reduction without loss of antitumor efficacy.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Melanoma/tratamento farmacológico , Melanoma/radioterapia , Neoplasias Uveais/tratamento farmacológico , Neoplasias Uveais/radioterapia , Animais , Bevacizumab , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Terapia Combinada , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Melanoma/patologia , Camundongos , Camundongos Nus , Carga Tumoral/efeitos dos fármacos , Neoplasias Uveais/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Eur Arch Otorhinolaryngol ; 270(10): 2745-9, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23430081

RESUMO

The objective of this study was to evaluate the potential detection of circulating tumor cells (CTCs) using the CellSearch (CS) Assay™ in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) and then to identify the clinical factors predictive of the presence of CTCs. The presence and number of CTCs were determined using the CS system before treatment, and in 10 healthy individuals (control group). The CS system was able to successfully identify the presence of CTCs in 8 of 49 patients (16 %) before therapy. No CTC was found in the control group. CTCs were detected before therapy in 1 of 19 patients (5 %) with N0 tumor and in 7 of 30 patients (23 %) with N1-2c tumor (p = 0.12; Fisher's exact test). CTCs were identified in a relatively low proportion of patients with locally advanced HNSCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Células Neoplásicas Circulantes/metabolismo , Idoso , Antígenos de Neoplasias/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Moléculas de Adesão Celular/metabolismo , Contagem de Células , Molécula de Adesão da Célula Epitelial , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Queratinas/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/diagnóstico , Neoplasias Orofaríngeas/metabolismo , Neoplasias Orofaríngeas/patologia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço
9.
Eur Arch Otorhinolaryngol ; 270(5): 1741-6, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23081673

RESUMO

The aim of this study was to assess the impact of the different subtypes of patient comorbidities on the outcomes of head and neck microvascular reconstruction. A total of 423 patients who underwent head and neck free flap reconstruction in our institution between 2000 and 2010 were included in this retrospective study. The impact of the different subtypes of patient comorbidities (as defined by the Kaplan-Feinstein Index) and other global health status-related factors on free flap success, local and general complications, postoperative mortality and length of stay was assessed in univariate and multivariate analysis. We found no correlation between patient comorbidities and free flap failure. In multivariate analysis, we demonstrated a significant correlation between tobacco consumption (p = 0.04) and local complications. Gastro-intestinal comorbidity (p = 0.005) and malnutrition (p = 0.02) were associated with a higher risk of fistula formation. Diabetes mellitus (p = 0.003), gastro-intestinal (p = 0.02), systemic (p = 0.02) and cardiac comorbidities (p = 0.03) were significant predictors of medical complications. We concluded that the different subtypes of patient comorbidities were relevant predictors of complications in head and neck microvascular reconstruction.


Assuntos
Retalhos de Tecido Biológico/irrigação sanguínea , Neoplasias de Cabeça e Pescoço/epidemiologia , Procedimentos de Cirurgia Plástica , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Vasculares , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/epidemiologia , Comorbidade , Diabetes Mellitus/epidemiologia , Feminino , Fístula , Gastroenteropatias/epidemiologia , Neoplasias de Cabeça e Pescoço/cirurgia , Nível de Saúde , Humanos , Tempo de Internação , Masculino , Desnutrição/epidemiologia , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco , Fumar/epidemiologia , Resultado do Tratamento , Adulto Jovem
10.
J Clin Med ; 12(3)2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36769779

RESUMO

BACKGROUND: The aims of this study were to evaluate the clinical outcomes and their predictive factors in locally advanced hypopharyngeal cancer (HC) patients included in a docetaxel-cisplatin-fluorouracil induction chemotherapy (ICT)-based larynx preservation (LP) program. METHODS: Between 2005 and 2021, 82 patients with a locally advanced resectable HC who received ICT in an LP program were included in this retrospective study. The predictors of oncologic and swallowing outcomes were determined in univariate and multivariate analyses. RESULTS: The three- and five-year overall survival (OS) rates were 67 and 54%, respectively. The T4 tumor stage was the only predictive factor of poor response to ICT (p = 0.03). In multivariate analysis, a T stage = 4 (p = 0.02), an ICT cycle number < 3 (p = 0.003) and the absence of a response to ICT (p = 0.03) were significantly associated with worse OS. A low body mass index before therapy (p = 0.003) and enteral nutrition during therapy (p = 0.005) were significantly associated with severity of dysphagia 6 months after treatment. CONCLUSIONS: The T stage, number of ICT cycles performed and response to ICT are the main predictors of oncologic outcomes. Patients with T4 HC are poor candidates for LP and should be referred to immediate radical surgery.

11.
J Clin Med ; 12(12)2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37373623

RESUMO

BACKGROUND: Many classifications exist to select patients with "high-risk" head and neck cutaneous squamous cell carcinoma (HNCSCC). OBJECTIVE: To compare the performance of the Brigham and Women's Hospital (BWH) classification with the performance of the American Joint Committee on Cancer 8th Edition (AJCC8), the Union for International Cancer Control 8th Edition (UICC8), and the National Comprehensive Cancer Network (NCCN) classifications. METHODS: In this single-center retrospective study, HNCSCC resected in a tertiary care center were classified as "low-risk" or "high-risk" tumors according to the four classifications. Rates of local recurrence (LR), lymph node recurrence (NR), and disease-specific death (DSD) were collected. The performance of each classification was then calculated in terms of homogeneity, monotonicity, and discrimination and compared. RESULTS: Two hundred and seventeen HNCSCC from 160 patients, with a mean age of 80 years, were included. For predicting the risk of any poor outcome and risk of NR, the BWH classification had the best specificity and positive predictive value. However, its concordance index was not significantly higher than that of the AJCC8 and UICC8 classifications. The NCCN classification was the least discriminant. CONCLUSIONS AND RELEVANCE: This study suggests that the BWH classification is the most appropriate for predicting the risk of poor outcomes in patients with HNCSCC when compared with the NCCN, UICC8, and AJCC8 classifications.

12.
J Clin Med ; 12(4)2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36835841

RESUMO

BACKGROUND: The aims of this study were to compare the survival outcomes of salvage vs. primary total laryngectomy (TL) in patients with locally advanced laryngeal or hypopharyngeal carcinoma and to determine their predictive factors. METHODS: Overall (OS), cause-specific (CSS) and recurrence-free survival (RFS) of primary vs. salvage TL were compared in univariate and multivariate analysis taking into account other potential predictive factors (tumor site, tumor stage, comorbidity level etc.). RESULTS: A total of 234 patients were included in this study. Five-year OS was 53% and 25% for the primary and salvage TL groups, respectively. Multivariate analysis confirmed the independent negative impact of salvage TL on OS (p = 0.0008), CSS (p < 0.0001) and RFS (p < 0.0001). Hypopharyngeal tumor site, ASA score ≥ 3, N-stage ≥ 2a and positive surgical margins were the main other predictors of oncologic outcomes. CONCLUSIONS: Salvage TL is associated with significantly worse survival rates than primary TL highlighting the need for careful selection of patients who are candidates for larynx preservation. The predictive factors of survival outcomes identified here should be considered in the therapeutic decision-making, especially in the setting of salvage TL, given the poor prognosis of these patients.

13.
J Clin Med ; 12(9)2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37176609

RESUMO

Nutritional support during radiotherapy is crucial to tolerating and completing oropharyngeal squamous cell carcinoma (OPSCC) treatment. The impact of HPV status on nutritional support is debated. The objective was to evaluate the rate of Reactive Feeding Tube (RFT) use and determine its prognostic factors during definitive radiotherapy for OPSCC. All OPSCC patients treated from 2009 to 2014 were included in this multicentric retrospective study. The impact of tumor p16 status on the risk of RFT was assessed through multivariate analyses. Among the 543 patients, 103 patients required an RFT (19.0%). The use of RFT differed between centers (5% to 32.4%). In multivariate analysis, only tongue base involvement and concurrent chemotherapy were significantly associated with RFT (OR = 2.18 and 3.7, respectively). Tongue base involvement and concomitant chemotherapy were prognostic factors for RFT. HPV status was not a prognostic factor for enteral nutrition during radiotherapy for OPSCC.

14.
Front Immunol ; 13: 903069, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36325333

RESUMO

Macrophages from human and mouse skin share phenotypic and functional features, but remain to be characterized in pathological skin conditions. Skin-resident macrophages are known to derive from embryonic precursors or from adult hematopoiesis. In this report, we investigated the origins, phenotypes and functions of macrophage subsets in mouse and human skin and in cutaneous squamous cell carcinoma (cSCC) using the spectral flow cytometry technology that enables cell autofluorescence to be considered as a full-fledged parameter. Autofluorescence identifies macrophage subsets expressing the CD206 mannose receptor in human peri-tumoral skin and cSCC. In mouse, all AF+ macrophages express the CD206 marker, a subset of which also displaying the TIM-4 marker. While TIM-4-CD206+ AF+ macrophages can differentiate from bone-marrow monocytes and infiltrate skin and tumor, TIM-4 identifies exclusively a skin-resident AF+ macrophage subset that can derive from prenatal hematopoiesis which is absent in tumor core. In mouse and human, AF+ macrophages from perilesional skin and cSCC are highly phagocytic cells contrary to their AF- counterpart, thus identifying autofluorescence as a bona fide marker for phagocytosis. Our data bring to light autofluorescence as a functional marker characterizing subsets of phagocytic macrophages in skin and cSCC. Autofluorescence can thus be considered as an attractive marker of function of macrophage subsets in pathological context.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Cutâneas , Adulto , Humanos , Animais , Camundongos , Carcinoma de Células Escamosas/patologia , Neoplasias Cutâneas/patologia , Fagocitose , Macrófagos/patologia , Monócitos
15.
Mol Oncol ; 16(16): 3001-3016, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35398964

RESUMO

A prevalence of around 26% of human papillomavirus (HPV) in head and neck squamous cell carcinoma (HNSCC) has been previously reported. HPV induced oncogenesis mainly involving E6 and E7 viral oncoproteins. In some cases, HPV viral DNA has been detected to integrate with the host genome and possibly contributes to carcinogenesis by affecting the gene expression. We retrospectively assessed HPV integration sites and signatures in 80 HPV positive patients with HNSCC, by using a double capture-HPV method followed by next-generation Sequencing. We detected HPV16 in 90% of the analyzed cohort and confirmed five previously described mechanistic signatures of HPV integration [episomal (EPI), integrated in a truncated form revealing two HPV-chromosomal junctions colinear (2J-COL) or nonlinear (2J-NL), multiple hybrid junctions clustering in a single chromosomal region (MJ-CL) or scattered over different chromosomal regions (MJ-SC) of the human genome]. Our results suggested that HPV remained episomal in 38.8% of the cases or was integrated/mixed in the remaining 61.2% of patients with HNSCC. We showed a lack of association of HPV genomic signatures to tumour and patient characteristics, as well as patient survival. Similar to other HPV associated cancers, low HPV copy number was associated with worse prognosis. We identified 267 HPV-human junctions scattered on most chromosomes. Remarkably, we observed four recurrent integration regions: PDL1/PDL2/PLGRKT (8.2%), MYC/PVT1 (6.1%), MACROD2 (4.1%) and KLF5/KLF12 regions (4.1%). We detected the overexpression of PDL1 and MYC upon integration by gene expression analysis. In conclusion, we identified recurrent targeting of several cancer genes such as PDL1 and MYC upon HPV integration, suggesting a role of altered gene expression by HPV integration during HNSCC carcinogenesis.


Assuntos
Alphapapillomavirus , Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Carcinogênese , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , DNA , Genômica , Neoplasias de Cabeça e Pescoço/genética , Humanos , Fatores de Transcrição Kruppel-Like , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/metabolismo , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
16.
Eur Arch Otorhinolaryngol ; 268(8): 1205-1212, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21607578

RESUMO

The impact of cervical lymph node metastases and the optimal surgical management of the neck in patients with papillary thyroid carcinoma (PTC) remain controversial. The objectives of this retrospective study were to determine, in patients with PTC, the predictive factors and the impact on tumor recurrence rate of cervical lymph node involvement, and to evaluate the oncologic results and the morbidity of central neck dissection (CND). We reviewed the records of patients who had undergone surgical treatment for PTC at our institution between 1990 and 2000. A total of 368 patients (86 men and 282 women) were included in this study. Young age (p = 0.02), tumor size (p = 0.001) and extrathyroidal tumor extension (p = 0.003) were significant predictive factors of cervical lymph node metastatic involvement (multivariate analysis). Initial metastatic cervical lymph node involvement was identified as an independent risk factor of tumor recurrence (multivariate analysis, p = 0.01). Metastatic lymph node(s) were found in prophylactic CND specimens in 31% of the patients. CND increased the risk of postoperative hypocalcemia (p = 0.008) and of permanent hypoparathyroidism (p = 0.002). In conclusion, cervical lymph node metastatic involvement at the time of initial surgery is an independent risk factor of tumor recurrence. CND provided an up-staging of more than 30% of patients with a clinically N0 neck, but was associated with significant morbidity regarding parathyroid function.


Assuntos
Linfonodos/patologia , Esvaziamento Cervical/métodos , Neoplasias da Glândula Tireoide/secundário , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma , Carcinoma Papilar , Feminino , Seguimentos , França/epidemiologia , Humanos , Incidência , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Adulto Jovem
17.
Front Immunol ; 12: 666233, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936105

RESUMO

The integrative analysis of tumor immune microenvironment (TiME) components, their interactions and their microanatomical distribution is mandatory to better understand tumor progression. Imaging Mass Cytometry (IMC) is a high dimensional tissue imaging system which allows the comprehensive and multiparametric in situ exploration of tumor microenvironments at a single cell level. We describe here the design of a 39-antibody IMC panel for the staining of formalin-fixed paraffin-embedded human tumor sections. We also provide an optimized staining procedure and details of the experimental workflow. This panel deciphers the nature of immune cells, their functions and their interactions with tumor cells and cancer-associated fibroblasts as well as with other TiME structural components known to be associated with tumor progression like nerve fibers and tumor extracellular matrix proteins. This panel represents a valuable innovative and powerful tool for fundamental and clinical studies that could be used for the identification of prognostic biomarkers and mechanisms of resistance to current immunotherapies.


Assuntos
Citometria por Imagem/métodos , Microambiente Tumoral/imunologia , Biomarcadores Tumorais/imunologia , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Progressão da Doença , Humanos , Imuno-Histoquímica , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Fluxo de Trabalho
18.
J Invest Dermatol ; 141(10): 2369-2379, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33831432

RESUMO

NK cells and tissue-resident innate lymphoid cells (ILCs) are innate effectors found in the skin. To investigate their temporal dynamics and specific functions throughout the development of cutaneous squamous cell carcinoma (cSCC), we combined transcriptomic and immunophenotyping analyses in mouse and human cSCCs. We identified an infiltration of NK cells and ILC1s as well as the presence of a few ILC3s. Adoptive transfer of NK cells in NK cell‒ and ILC-deficient Nfil3-/- mice revealed a role for NK cells in early control of cSCC. During tumor progression, we identified a population skewing with the infiltration of atypical ILC1 secreting inflammatory cytokines but reduced levels of IFN-γ at the papilloma stage. NK cells and ILC1s were functionally impaired, with reduced cytotoxicity and IFN-γ secretion associated with the downregulation of activating receptors. They also showed a high degree of heterogeneity in mouse and human cSCCs with the expression of several markers of exhaustion, including TIGIT on NK cells and PD-1 and TIM-3 on ILC1s. Our data show an enrichment in inflammatory ILC1 at the precancerous stage together with impaired antitumor functions in NK cells and ILC1 that could contribute to the development of cSCC and thus suggest that future immunotherapies should take both ILC populations into account.


Assuntos
Carcinoma de Células Escamosas/imunologia , Células Matadoras Naturais/fisiologia , Linfócitos/fisiologia , Neoplasias Cutâneas/imunologia , Transferência Adotiva , Animais , Fatores de Transcrição de Zíper de Leucina Básica/fisiologia , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/patologia , Humanos , Imunidade Inata , Células Matadoras Naturais/imunologia , Linfócitos/imunologia , Camundongos , Receptor 1 Desencadeador da Citotoxicidade Natural/análise , Estadiamento de Neoplasias , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologia
19.
Eur J Cancer ; 143: 168-177, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33333482

RESUMO

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.


Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Neoplasias Orofaríngeas/tratamento farmacológico , Terapia de Salvação/métodos , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico
20.
Eur J Surg Oncol ; 47(6): 1389-1397, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33390333

RESUMO

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.


Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Recidiva Local de Neoplasia/cirurgia , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/terapia , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Cetuximab/uso terapêutico , Quimiorradioterapia Adjuvante , Cisplatino/uso terapêutico , Feminino , Humanos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/metabolismo , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/metabolismo , Radioterapia Adjuvante , Estudos Retrospectivos , Taxa de Sobrevida
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