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2.
Clin Adv Periodontics ; 9(2): 55-58, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31498573

RESUMO

INTRODUCTION: The bioresorbable polymer poly(lactide-co-glycolic acid) (PLGA) coated ß-tricalcium phosphate (ß-TCP) (ß-TCP/PLGA) bone substitute hardens into a stable and porous hard tissue scaffold when exposed to body fluids. Effectiveness of the novel alloplast has been examined in edentulous ridge preservation (ERP) following tooth extraction with subsequent early endosseous dental implant placement; however, it is not clear that the biomaterial is capable of maintaining the edentulous ridge volume to allow for late implant placement due to the rapid bioresorption property of ß-TCP. The purpose of this case series is to determine if the ß-TCP/PLGA bone substitute is a desirable material for ERP followed by late implant placement. CASE PRESENTATION: Two patients were treated with ERP and prepared for future endosseous dental implant placement. The ß-TCP/PLGA alloplast was placed in the extraction socket. The grafted site of one of the patients was covered by a bioresorbable membrane due to the critical loss of buccal plate. Endosseous dental implant fixtures were placed in both patients 10 months following ERP. Bone core specimens were taken at the time of endosseous dental implant fixture placement and were prepared for histologic assessment. The edentulous ridge volume was successfully maintained for dental implant placement in both cases. Histomorphometric analysis showed that the ß-TCP/PLGA alloplast was replaced by newly formed bone with or without guided bone regeneration membrane placement, 54.1% and 34.6%, respectively. CONCLUSION: The ß-TCP/PLGA bone substitute exhibited effectiveness in edentulous ridge preservation followed by late endosseous dental implant placement.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31400990

RESUMO

OBJECTIVES: Plasmacytoid cells (PLCs) in salivary pleomorphic adenoma (SPA) are regarded as modified neoplastic myoepithelia and define plasmacytoid myoepithelioma (pMYO). However, histochemically, immunohistochemically and ultrastructurally, PLCs fail to demonstrate frank myogenous properties. Epithelial-mesenchymal transition (EMT) may explain the phenotypes in SPA. Our aim was to evaluate (1) PLCs with accepted or purported myoepithelial and EMT-related markers; and (2) pMYOs for PLAG1 aberrations by using fluorescence in situ hybridization. STUDY DESIGN: Eight SPAs with or without PLC-predominance and 3 pMYOs were immunohistochemically studied. RESULTS: PLCs in SPA and pMYO exhibited strong, scattered to diffuse positivity for K7, rare K14 positivity and were mostly negative for α-smooth muscle actin, h-caldesmon, and p63/p40. S100 staining was strong and diffuse, whereas calponin was variable. DOG1 was negative. PLCs in pMYO and PLC-rich SPA exhibited selective or diffuse WT1 and D2-40 immunoreactivity. EMT markers SNAIL/SLUG exhibited strong and variable immunoreactivity in PLCs in contrast to weak or absent E-cadherin expression. SOX10 was diffusely and strongly positive. PLAG1 rearrangement was present in 1 pMYO. CONCLUSIONS: PLCs mostly fail to express myoepithelial markers; PLCs are neoplastic cells adapting to microenvironmental changes and capable of EMT; and tumors composed solely of PLCs are apparently SPAs depleted of a ductal component.

4.
Am J Surg Pathol ; 43(7): 885-897, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31021855

RESUMO

Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy, but categorization is complicated by variability in grading systems and uncertain prognostic significance of MAML2 rearrangement. The aims of this study were to determine the prognostic significance of MEC grading systems and MAML2 rearrangement status. Fifty-three carcinomas originally diagnosed as MEC (45 primary; 8 recurrent) of major and minor salivary glands were graded according to modified Healey, Brandwein, AFIP, and Katabi systems. Fluorescence in situ hybridization for MAML2 rearrangement was performed. Clinical features and outcomes were recorded. Twenty-five (47%) carcinomas scored the same in all grading systems. The most common histologic feature leading to a diagnosis of intermediate grade was isolated solid growth. Brandwein assigned the highest percentage of high grade (29%) and AFIP the highest percentage of low grade (80%). MAML2 was rearranged in 37/46 (80%) cases. Forty-three (81%) were morphologically compatible with MEC, and these were more likely to be low-intermediate grade and MAML2-rearranged. Of primary carcinomas, 6 (13%) recurred. Statistically significant univariate risk factors for recurrence included non-MEC morphology, stage T4, and high Brandwein grade. Margin status, MAML2 rearrangement, and isolated solid growth were not predictive of recurrence. A binary grading system (Brandwein high vs. low-plus-intermediate) could be considered to better reflect biological behavior in MEC. Our study confirms that MAML2 wildtype tumors more likely represent high grade non-MECs, and prior studies demonstrating worse prognosis in MAML2-nonrearranged MECs may be diluted by high-grade non-MECs.

6.
Lab Invest ; 2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30401959

RESUMO

Enumeration of tumor-infiltrating lymphocytes (TILs) in H&E stained tissue sections has demonstrated limited value in predicting immune responses to cancer immunotherapy, likely reflecting the diversity of cell types and immune activation states among tumor infiltrates. Multiparametric flow cytometry enables robust phenotypic and functional analysis to distinguish suppression from activation, but tissue dissociation eliminates spatial context. Multiplex methods for immunohistochemistry (IHC) are emerging, but these interrogate only a single tissue section at a time. Here, we report transparent tissue tomography (T3) as a tool for three-dimensional (3D) imaging cytometry in the complex architecture of the tumor microenvironment, demonstrating multiplexed immunofluorescent analysis in core needle biopsies. Using T3 imaging, image processing and machine learning to map CD3+CD8+ cytotoxic T cells (CTLs) in whole core needle biopsies from Her2+ murine mammary tumors and human head and neck surgical specimens revealed marked inhomogeneity within single needle cores, confirmed by serial section IHC. Applying T3 imaging cytometry, we discovered a strong spatial correlation between CD3+CD8+ CTLs and microvasculature in the EGFR+ parenchyma, revealing significant differences among head and neck cancer patients. These results show that T3 offers simple and rapid access to three-dimensional and quantitative maps of the tumor microenvironment and immune infiltrate, offering a new diagnostic tool for personalized cancer immunotherapy.

8.
J Clin Oncol ; : JCO1800684, 2018 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-30188786

RESUMO

Purpose The College of American Pathologists produced an evidence-based guideline on testing, application, interpretation, and reporting of human papillomavirus (HPV) and surrogate marker tests in head and neck carcinomas that was determined to be relevant to the American Society of Clinical Oncology (ASCO) membership. Methods The College of American Pathologists HPV Testing in Head and Neck Carcinomas guideline was reviewed by ASCO content experts for clinical accuracy and by methodologists for developmental rigor. On favorable review, an ASCO Expert Panel was convened to review the guideline contents and recommendations. Results The ASCO Expert Panel determined that the recommendations from the HPV Testing in Head and Neck Carcinomas guideline, published in 2018, are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorsed the guideline and added minor qualifying statements. Recommendations It is recommended that HPV tumor status should be determined for newly diagnosed oropharyngeal squamous cell carcinomas. HPV tumor status testing may be performed by surrogate marker p16 immunohistochemistry either on the primary tumor or from cervical nodal metastases only if an oropharyngeal primary tumor is present. The threshold for positivity is at least 70% nuclear and cytoplasmic expression with at least moderate to strong intensity. Additional confirmatory testing may be done at the discretion of the pathologist and/or treating clinician. Pathologists should not routinely determine HPV tumor status in nonsquamous carcinomas of the oropharynx or non-oropharyngeal squamous cell carcinomas of the head and neck. When there is uncertainty of histologic type or whether a poorly differentiated oropharyngeal tumor is nonsquamous, HPV tumor status testing may be warranted and at the discretion of the pathologist and/or treating clinician. Additional information is available at: www.asco.org/head-neck-cancer-guidelines .

9.
Histopathology ; 2018 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-30144145

RESUMO

AIMS AND OBJECTIVES: Cervical lymph node metastasis in head and neck squamous cell carcinoma (HNSCC) is common. Pre-operative chemoradiotherapy (preCRT) and postoperative chemoradiotherapy (postCRT) is frequently employed in such patients. The prognostic value of viable SCC, treatment effect or no SCC in resected lymph nodes in patients who received or did not receive preCRT and postCRT was investigated. METHODS AND RESULTS: Resected cervical lymph nodes from 146 patients with HNSCC were evaluated for viable SCC, treatment effect or no SCC. Immunostains for Ki67, cyclin D1, caspase 3 and H2AFX were performed on viable SCC or nucleate keratin debris. Clinical and histological data were correlated with tumour recurrence or persistence. Patients with nucleate keratin debris in lymph nodes had outcomes similar to those with diffuse treatment effect and no SCC. Viable tumour in lymph nodes was associated with worse prognosis in patients who received preCRT (P = 0.01). This relative worsening of prognosis was not observed in patients with oropharyngeal SCC or recurrent disease. Lower proliferation index in lymph node SCC was associated with preCRT and with worse outcomes (P = 0.0002). Overall, patients who received preCRT or postCRT had outcomes not significantly different from those who did not. CONCLUSION: The presence of viable SCC in cervical lymph nodes has prognostic import when taken in context with the patient's history. Viable SCC in lymph nodes was significantly associated with worse outcome among patients with non-oropharyngeal SCC who received preCRT. Nucleate keratin debris should not be considered viable SCC in lymph nodes.

10.
J Natl Cancer Inst ; 110(3)2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29617836

RESUMO

Background: We have previously shown that gene expression profiles of oral leukoplakia (OL) may improve the prediction of oral cancer (OC) risk. To identify new targets for prevention, we performed a systematic survey of transcripts associated with an increased risk of oral cancer and overexpressed in OC vs normal mucosa (NM). Methods: We used gene expression profiles of 86 patients with OL and available outcomes from a chemoprevention trial of OC and NM. MET expression was evaluated using immunohistochemistry in 120 OL patients, and its association with OC development was tested in multivariable analysis. Sensitivity to pharmacological Met inhibition was tested invitro in premalignant and OC cell lines (n = 33) and invivo using the 4-NQO model of oral chemoprevention (n = 20 mice per group). All statistical tests were two-sided. Results: The overlap of 693 transcripts associated with an increased risk of OC with 163 transcripts overexpressed in OC compared with NM led to the identification of 23 overlapping transcripts, including MET. MET overexpression in OL was associated with a hazard ratio of 3.84 (95% confidence interval = 1.59 to 9.27, P = .003) of developing OC. Met activation was found in OC and preneoplastic cell lines. Crizotinib activity in preneoplastic and OC cell lines was comparable. ARQ 197 was more active in preneoplastic compared with OC cell lines. In the 4-NQO model, squamous cell carcinoma, dysplasia, and hyperkeratosis were observed in 75.0%, 15.0%, and 10.0% in the control group, and in 25.0%, 70.0%, and 5.0% in the crizotinib group (P < .001). Conclusion: Together, these data suggest that MET activation may represent an early driver in oral premalignancy and a target for chemoprevention of OC.

11.
J Am Dent Assoc ; 149(4): 233-234, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29599016
12.
Blood Adv ; 2(2): 146-150, 2018 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-29365323

RESUMO

Next-generation sequencing (NGS)-based targeted gene capture panels are used to profile hematopoietic malignancies to guide prognostication and treatment decisions. Because these panels include genes associated with hereditary hematopoietic malignancies (HHMs), we hypothesized that these panels could identify pathogenic germ line variants in malignant cells, thereby identifying patients at risk for HHMs. In total, pathogenic or likely pathogenic variants in ANKRD26, CEBPA, DDX41, ETV6, GATA2, RUNX1, or TP53 were identified in 74 (21%) of 360 patients. Germ line tissue was available for 24 patients with 25 pathogenic or likely pathogenic variants with variant allele frequencies >0.4. Six (24%) of these 25 variants were of germ line origin. Three DDX41 variants, 2 GATA2 variants, and a TP53 variant previously implicated in Li-Fraumeni syndrome were of germ line origin. No likely pathogenic/pathogenic germ line variants possessed variant allele frequencies <0.4. This study demonstrates that NGS-based prognostic panels may identify individuals at risk for HHMs despite not being designed for this purpose. Furthermore, variants known to cause Li-Fraumeni syndrome as well as known pathogenic variants in genes such as DDX41 and GATA2 are especially likely to be of germ line origin. Thus, tumor-based panels may augment, but should not replace, comprehensive germ line-based testing and counseling.

13.
Head Neck Pathol ; 12(1): 95-104, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28681314

RESUMO

With the advent of targeted therapies, expression of sex hormone receptors and HER-2 in salivary gland tumors (SGTs) is of clinical interest. Previous reports of estrogen (ER) and progesterone (PR) receptor expression have varied. Androgen receptor (AR) and HER-2 overexpression are frequently reported in salivary duct carcinoma (SDC), but have not been studied systematically in other SGTs. This study examines ER, PR, AR, and HER-2 expression in SGTs. Immunohistochemistry for ER, PR, AR, and HER-2 was performed on 254 SGTs (134 malignant). ER, PR, and AR expression was scored using Allred system. HER-2 expression was scored using Dako HercepTest guidelines. FISH for HER-2 amplification was performed on select cases with HER-2 overexpression (2-3+). No SGT demonstrated strong expression of ER or PR. Combined strong AR and HER-2 expression was seen in 22 carcinomas: 14/25 SDC, 3/16 poorly differentiated, two oncocytic, and one each carcinoma ex pleomorphic adenoma, squamous cell, and intraductal carcinoma. Eighteen additional high grade carcinomas had HER-2 overexpression with absent, weak, or moderate AR expression; eight high grade carcinomas had isolated strong AR expression with 0-1+ HER-2 staining. Of 15 tested cases, six demonstrated HER-2 amplification by FISH, all of which had 3+ immunoreactivity. Neither benign nor malignant SGTs had strong expression of ER or PR. None of the benign SGTs overexpressed AR or HER-2. Coexpression of AR and HER-2 should not define SDC, but immunostaining should be considered in high grade salivary carcinomas, as some show overexpression and may benefit from targeted therapy.


Assuntos
Biomarcadores Tumorais/análise , Receptor ErbB-2/biossíntese , Neoplasias das Glândulas Salivares/patologia , Humanos , Receptor ErbB-2/análise , Receptores Androgênicos/análise , Receptores Androgênicos/biossíntese , Receptores Estrogênicos/análise , Receptores Estrogênicos/biossíntese , Receptores de Progesterona/análise , Receptores de Progesterona/biossíntese , Estudos Retrospectivos
14.
J Am Dent Assoc ; 148(11): 797-813.e52, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29080605

RESUMO

BACKGROUND: Oral squamous cell carcinoma is the most common manifestation of malignancy in the oral cavity. Adjuncts are available for clinicians to evaluate lesions that seem potentially malignant. In this systematic review, the authors summarized the available evidence on patient-important outcomes, diagnostic test accuracy (DTA), and patients' values and preferences (PVPs) when using adjuncts for the evaluation of clinically evident lesions in the oral cavity. TYPES OF STUDIES REVIEWED: The authors searched for preexisting systematic reviews and assessed their quality using the Assessing the Methodological Quality of Systematic Reviews tool. The authors updated the selected reviews and searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials and DTA and PVPs studies. Pairs of reviewers independently conducted study selection, data extraction, and assessment of the certainty in the evidence by using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: The authors identified 4 existing reviews. DTA reviews included 37 studies. The authors retrieved 7,534 records, of which 9 DTA and 10 PVPs studies were eligible. Pooled sensitivity and specificity of adjuncts ranged from 0.39 to 0.96 for the evaluation of innocuous lesions and from 0.31 to 0.95 for the evaluation of suspicious lesions. Cytologic testing used in suspicious lesions appears to have the highest accuracy among adjuncts (sensitivity, 0.92; 95% confidence interval, 0.86 to 0.98; specificity, 0.94; 95% confidence interval, 0.88 to 0.99; low-quality evidence). CONCLUSIONS AND PRACTICAL IMPLICATIONS: Cytologic testing appears to be the most accurate adjunct among those included in this review. The main concerns are the high rate of false-positive results and serious issues of risk of bias and indirectness of the evidence. Clinicians should remain skeptical about the potential benefit of any adjunct in clinical practice.

15.
J Am Dent Assoc ; 148(10): 712-727.e10, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28958308

RESUMO

BACKGROUND: An expert panel convened by the American Dental Association (ADA) Council on Scientific Affairs and the Center for Evidence-Based Dentistry conducted a systematic review and formulated clinical recommendations to inform primary care clinicians about the potential use of adjuncts as triage tools for the evaluation of lesions, including potentially malignant disorders (PMDs), in the oral cavity. TYPES OF STUDIES REVIEWED: This is an update of the ADA's 2010 recommendations on the early diagnosis of PMDs and oral squamous cell carcinoma. The authors conducted a systematic search of the literature in MEDLINE and Embase via Ovid and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials and diagnostic test accuracy studies. The authors used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty in the evidence and to move from the evidence to the decisions. RESULTS: The panel formulated 1 good practice statement and 6 clinical recommendations that concluded that no available adjuncts demonstrated sufficient diagnostic test accuracy to support their routine use as triage tools during the evaluation of lesions in the oral cavity. For patients seeking care for suspicious lesions, immediate performance of a biopsy or referral to a specialist remains the single most important recommendation for clinical practice. In exceptional cases, when patients decline a biopsy or live in rural areas with limited access to care, the panel suggested that cytologic testing may be used to initiate the diagnostic process until a biopsy can be performed (conditional recommendation, low-quality evidence). CONCLUSIONS AND PRACTICAL IMPLICATIONS: The authors urge clinicians to remain alert and take diligent action when they identify a PMD. The authors emphasize the need for counseling because patients may delay diagnosis because of anxiety and denial.

16.
PLoS One ; 12(5): e0177884, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28542361

RESUMO

Glucocorticoids promote neutrophilic inflammation, the mechanisms of which are poorly characterized. Using a lipopolysaccharide (LPS)-induced acute murine lung injury model, we determined the role of granulocyte colony-stimulating factor (G-CSF) in mouse lung neutrophil numbers in the absence and presence of dexamethasone, a potent glucocorticoid. G-CSF was blocked using a neutralizing antibody. Airway neutrophil numbers, cytokine levels, and lung injury parameters were measured. Glucocorticoid treatment maintained LPS-induced airway G-CSF while suppressing TNF and IL-6. The addition of anti-G-CSF antibodies enabled dexamethasone to decrease airway G-CSF, neutrophils, and lung injury scores. In LPS-challenged murine lungs, structural cells and infiltrating leukocytes produced G-CSF. In vitro using BEAS 2B bronchial epithelial cells, A549 lung epithelial cells, human monocyte-derived macrophages, and human neutrophils, we found that dexamethasone and proinflammatory cytokines synergistically induced G-CSF. Blocking G-CSF production in BEAS 2B cells using shRNAs diminished the ability of BEAS 2B cells to protect neutrophils from undergoing spontaneous apoptosis. These data support that G-CSF plays a role in upregulation of airway neutrophil numbers by dexamethasone in the LPS-induced acute lung injury model.


Assuntos
Dexametasona/farmacologia , Fator Estimulador de Colônias de Granulócitos/antagonistas & inibidores , Lipopolissacarídeos/toxicidade , Lesão Pulmonar/tratamento farmacológico , Pulmão/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Animais , Células Cultivadas , Citocinas/metabolismo , Glucocorticoides/farmacologia , Humanos , Pulmão/metabolismo , Pulmão/patologia , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/metabolismo , Neutrófilos/patologia
17.
Oncotarget ; 8(12): 18726-18734, 2017 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-27244893

RESUMO

MET is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC) and degraded by c-CBL E3-ubiquitin ligase. We investigated genetic variations of c-CBL in HNSCC and the relationship between c-CBL and MET expression. High MET, low c-CBL expression was detected in 10 cell lines and 73 tumor tissues. Two novel mutations (L254S, L281F), and the single nucleotide polymorphism (SNP) P782L were identified from archival tumor tissues. 27.3% of loss of heterozygosity was found at CBL locus. Ectopic expression of wild-type c-CBL in SCC-35 cells downregulated MET expression and decreased cell viability. These results suggest MET overexpression is related to altered c-CBL expression, which may influence tumorigenesis.


Assuntos
Carcinoma de Células Escamosas/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias de Cabeça e Pescoço/genética , Proteínas Proto-Oncogênicas c-cbl/genética , Proteínas Proto-Oncogênicas c-met/genética , Carcinoma de Células Escamosas/patologia , Análise Mutacional de DNA , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Immunoblotting , Imuno-Histoquímica , Perda de Heterozigosidade , Carcinoma de Células Escamosas de Cabeça e Pescoço , Análise Serial de Tecidos
19.
Artigo em Inglês | MEDLINE | ID: mdl-27727113

RESUMO

Screening for oral cancer should be defined as the application of a test to people who are apparently free of disease to identify those who may have oral cancer and to distinguish them from those who may not. The aim of the test is not to be diagnostic but to identify changes that may be the earliest signs of impending disease. Defined in this way, screening is an ongoing public health measure, often funded by governments. A screening program must do no harm and must be cost effective. Governments demand that strict evidence of benefits and cost effectiveness be met before a program may be implemented. Although many studies have investigated the utility of potential screening tests, there have been few evaluations of screening programs and only one randomized controlled trial. Systematic reviews have concluded that there is insufficient evidence to show that oral cancer screening can reduce mortality from oral cancer, and to date, no country has implemented a formal oral cancer screening program. This paper reviews this evidence and tries to identify the barriers to screening and suggests areas of focus for future research.


Assuntos
Detecção Precoce de Câncer , Saúde Global , Programas de Rastreamento , Neoplasias Bucais/diagnóstico , Humanos
20.
Int J Radiat Oncol Biol Phys ; 96(1): 21-9, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27511844

RESUMO

PURPOSE: The role of cetuximab in the treatment of locoregionally advanced head and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase 2 randomized study, we investigated the addition of cetuximab to both induction chemotherapy (IC) and hyperfractionated or accelerated chemoradiation. METHODS AND MATERIALS: Patients with LA-HNSCC were randomized to receive 2 cycles of weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent cetuximab, 5-fluorouracil, hydroxyurea, and 1.5 Gy twice-daily radiation therapy every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated radiation therapy with delayed concomitant boost to 72 Gy in 42 fractions). The primary endpoint was progression-free survival (PFS), with superiority compared with historical control achieved if either arm had 2-year PFS ≥70%. RESULTS: 110 patients were randomly assigned to either Cetux-FHX (n=57) or Cetux-PX (n=53). The overall response rate to IC was 91%. Severe toxicity on IC was limited to rash (23% grade ≥3) and myelosuppression (38% grade ≥3 neutropenia). The 2-year rates of PFS for both Cetux-FHX (82.5%) and Cetux-PX (84.9%) were significantly higher than for historical control (P<.001). The 2-year overall survival (OS) was 91.2% for Cetux-FHX and 94.3% for Cetux-PX. With a median follow-up time of 72 months, there were no significant differences in PFS (P=.35) or OS (P=.15) between the treatment arms. The late outcomes for the entire cohort included 5-year PFS, OS, locoregional failure, and distant metastasis rates of 74.1%, 80.3%, 15.7%, and 7.4%, respectively. The 5-year PFS and OS were 84.4% and 91.3%, respectively, among human papillomavirus (HPV)-positive patients and 65.9% and 72.5%, respectively, among HPV-negative patients. CONCLUSIONS: The addition of cetuximab to IC and chemoradiation was tolerable and produced long-term control of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further investigation of cetuximab may be warranted in the neoadjuvant setting and with non-platinum-based chemoradiation.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Escamosas/terapia , Cetuximab/administração & dosagem , Quimiorradioterapia/métodos , Fracionamento da Dose de Radiação , Neoplasias de Cabeça e Pescoço/terapia , Recidiva Local de Neoplasia/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Dosagem Radioterapêutica , Carcinoma de Células Escamosas de Cabeça e Pescoço , Taxa de Sobrevida , Resultado do Tratamento
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