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PURPOSE: The rapid spread of the SARS-CoV-2 pandemic around the world caused most healthcare services to turn substantial attention to treatment of these patients and also to alter the structure of healthcare systems to address an infectious disease. As a result, many cancer patients had their treatment deferred during the pandemic, increasing the time-to-treatment initiation, the number of untreated patients (which will alter the dynamics of healthcare delivery in the post-pandemic era) and increasing their risk of death. Hence, we analyzed the impact on global cancer mortality considering the decline in oncology care during the COVID-19 outbreak using head and neck cancer, a known time-dependent disease, as a model. METHODS: An online practical tool capable of predicting the risk of cancer patients dying due to the COVID-19 outbreak and also useful for mitigation strategies after the peak of the pandemic has been developed, based on a mathematical model. The scenarios were estimated by information of 15 oncological services worldwide, given a perspective from the five continents and also some simulations were conducted at world demographic data. RESULTS: The model demonstrates that the more that cancer care was maintained during the outbreak and also the more it is increased during the mitigation period, the shorter will be the recovery, lessening the additional risk of dying due to time-to-treatment initiation. CONCLUSIONS: This impact of COVID-19 pandemic on cancer patients is inevitable, but it is possible to minimize it with an effort measured by the proposed model.
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COVID-19 , Carcinoma de Células Escamosas/epidemiologia , Atenção à Saúde , Neoplasias de Cabeça e Pescoço/epidemiologia , SARS-CoV-2 , Tempo para o Tratamento , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/mortalidade , Saúde Global , Neoplasias de Cabeça e Pescoço/etiologia , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Modelos Teóricos , Fatores de RiscoRESUMO
Oral tumor microenvironment is characterized by chronic inflammation signified with infiltrating leukocytes and soluble mediators which cause immune suppression. However, how immunosuppressive cells like myeloid-derived suppressor cells (MDSCs) maintain the immunosuppressive tumor microenvironment and influence T cell function in oral squamous cell carcinoma (OSCC) patients remains poorly understood. In the present study, we found that percentages of MDSCs were higher in oral cancer patients compared to healthy individuals and correlated with cancer stage. Monocytic MDSCs (M-MDSCs) were prevalent in the periphery, while granulocytic/polymorphonuclear subset dominated the tumor compartment. M-MDSCs suppressed the lymphocyte proliferation and decreased the CD3-ζ (zeta) chain expression and interferon gamma production. The percentage of M-MDSCs in peripheral blood correlated inversely with CD3-ζ chain expression in T cells of these patients. Interleukin 6 (IL-6)-induced phosphorylated STAT3-regulated programmed cell death ligand 1, CCAAT/enhancer-binding proteins alpha and beta and Interleukin 10 expression in MDSCs. MDSCs inhibited TGF-ß-driven generation of induced regulatory T cells in vitro. M-MDSCs secreted interleukins IL-6, IL-1ß, IL-23 and PGE2 and facilitated T-helper 17 (Th17) cell differentiation which utilizes nitric oxide synthase and cyclooxygenase 2 enzyme activity. Interestingly, OSCC patients showed increased levels of Th17 cells in peripheral blood and tumor tissue. Thus, increased frequency of MDSCs, Th17 cells and decreased expression of CD3-ζ chain portray T cell tolerance and chronic inflammatory state facilitating tumor growth.
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Carcinoma de Células Escamosas/genética , Neoplasias Bucais/genética , Células Supressoras Mieloides/imunologia , Células Th17/imunologia , Diferenciação Celular , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Oral squamous cell carcinoma (OSCC) is highly prevalent in south and southeast Asia. Many (30-50%) OSCC patients develop lymph node metastasis (LNM), which is the most important prognostic factor in OSCC. To identify genomic correlates of LNM, we compared exome sequences and copy number variation data of blood and tumor DNA from highly contrasting subgroups of patients to reduce false inferences-(i) patients with LNM and (ii) patients with late stage disease but without LNM. We found that LNM is associated with (i) specific hotspot somatic mutations in TP53 and CASP8; (ii) rare nonsilent germline mutations in BRCA2 and FAT1; (iii) mutations in mito-G2/M and nonhomologous end joining (NHEJ) pathways; (iv) recurrent deletion of genes for DNA repair by homologous recombination; and (v) chromosomal instability. LN+ patients with NHEJ pathway mutations have longer disease-free survival. Five genomic features have a high predictive value of LNM.
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Instabilidade Cromossômica/genética , Reparo do DNA/genética , Linfonodos/patologia , Metástase Linfática/genética , Metástase Linfática/patologia , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Variações do Número de Cópias de DNA/genética , Intervalo Livre de Doença , Feminino , Deleção de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genéticaRESUMO
BACKGROUND: Because the addition of nimotuzumab to chemoradiation in patients with locally advanced head and neck cancer improved outcomes in a phase 2 study, the authors conducted a phase 3 study to confirm these findings. METHODS: This open-label, investigator-initiated, phase 3, randomized trial was conducted from 2012 to 2018. Adult patients with locally advanced head and neck cancer who were fit for radical chemoradiation were randomized 1:1 to receive either radical radiotherapy (66-70 grays) with concurrent weekly cisplatin (30 mg/m2 ) (CRT) or the same schedule of CRT with weekly nimotuzumab (200 mg) (NCRT).The primary endpoint was progression-free survival (PFS); key secondary endpoints were disease-free survival (DFS), duration of locoregional control (LRC), and overall survival (OS). An intent-to-treat analysis also was performed. RESULTS: In total, 536 patients were allocated equally to both treatment arms. The median follow-up was 39.13 months. The addition of nimotuzumab improved PFS (hazard ratio [HR], 0.69; 95% CI, 0.53-0.89; P = .004), LRC (HR, 0.67; 95% CI, 0.50-0.89; P = .006), and DFS (HR, 0.71; 95% CI, 0.55-0.92; P = .008) and had a trend toward improved OS (HR, 0.84; 95% CI, 0.65-1.08; P = .163). Grade 3 through 5 adverse events were similar between the 2 arms, except for a higher incidence of mucositis in the NCRT arm (66.7% vs 55.8%; P = .01). CONCLUSIONS: The addition of nimotuzumab to concurrent weekly CRT improves PFS, LRC, and DFS. This combination provides a novel alternative therapeutic option to a 3-weekly schedule of 100 mg/m2 cisplatin in patients with locally advanced head and neck cancer who are treated with radical-intent CRT.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos/uso terapêutico , Quimiorradioterapia/métodos , Cisplatino/uso terapêutico , Neoplasias de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosite/etiologia , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Trombocitopenia/etiologia , Adulto JovemRESUMO
BACKGROUND: Whether patients with early-stage oral cancers should be treated with elective neck dissection at the time of the primary surgery or with therapeutic neck dissection after nodal relapse has been a matter of debate. METHODS: In this prospective, randomized, controlled trial, we evaluated the effect on survival of elective node dissection (ipsilateral neck dissection at the time of the primary surgery) versus therapeutic node dissection (watchful waiting followed by neck dissection for nodal relapse) in patients with lateralized stage T1 or T2 oral squamous-cell carcinomas. Primary and secondary end points were overall survival and disease-free survival, respectively. RESULTS: Between 2004 and 2014, a total of 596 patients were enrolled. As prespecified by the data and safety monitoring committee, this report summarizes results for the first 500 patients (245 in the elective-surgery group and 255 in the therapeutic-surgery group), with a median follow-up of 39 months. There were 81 recurrences and 50 deaths in the elective-surgery group and 146 recurrences and 79 deaths in the therapeutic-surgery group. At 3 years, elective node dissection resulted in an improved rate of overall survival (80.0%; 95% confidence interval [CI], 74.1 to 85.8), as compared with therapeutic dissection (67.5%; 95% CI, 61.0 to 73.9), for a hazard ratio for death of 0.64 in the elective-surgery group (95% CI, 0.45 to 0.92; P=0.01 by the log-rank test). At that time, patients in the elective-surgery group also had a higher rate of disease-free survival than those in the therapeutic-surgery group (69.5% vs. 45.9%, P<0.001). Elective node dissection was superior in most subgroups without significant interactions. Rates of adverse events were 6.6% and 3.6% in the elective-surgery group and the therapeutic-surgery group, respectively. CONCLUSIONS: Among patients with early-stage oral squamous-cell cancer, elective neck dissection resulted in higher rates of overall and disease-free survival than did therapeutic neck dissection. (Funded by the Tata Memorial Centre; ClinicalTrials.gov number, NCT00193765.).
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Procedimentos Cirúrgicos Eletivos , Neoplasias Bucais/cirurgia , Esvaziamento Cervical , Neoplasias de Células Escamosas/cirurgia , Adulto , Idoso , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Estadiamento de Neoplasias , Neoplasias de Células Escamosas/mortalidade , Estudos Prospectivos , Análise de Sobrevida , Conduta ExpectanteRESUMO
PURPOSE: Thyroid nodules are of common occurrence in the general population. About a fourth of these nodules are indeterminate on aspiration cytology placing many a patient at risk of unwanted surgery. The purpose of this review is to discuss various molecular markers described to date and place their role in proper perspective. This review covers the fundamental role of the signaling pathways and genetic changes involved in thyroid carcinogenesis. The current literature on the prognostic significance of these markers is also described. METHODS: PubMed was used to search relevant articles. The key terms "thyroid nodules", "thyroid cancer papillary", "carcinoma papillary follicular", "carcinoma papillary", "adenocarcinoma follicular" were searched in MeSH, and "molecular markers", "molecular testing", mutation, BRAF, RAS, RET/PTC, PAX 8, miRNA, NIFTP in title and abstract fields. Multiple combinations were done and a group of experts in the subject from the International Head and Neck Scientific Group extracted the relevant articles and formulated the review. RESULTS: There has been considerable progress in the understanding of thyroid carcinogenesis and the emergence of numerous molecular markers in the recent years with potential to be used in the diagnostic algorithm of these nodules. However, their precise role in routine clinical practice continues to be a contentious issue. Majority of the studies in this context are retrospective and impact of these mutations is not independent of other prognostic factors making the interpretation difficult. CONCLUSION: The prevalence of these mutations in thyroid nodule is high and it is a continuously evolving field. Clinicians should stay informed as recommendation on the use of these markers is expected to evolve.
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Carcinoma/genética , Carcinoma/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Biomarcadores/metabolismo , Carcinoma/patologia , Humanos , Mutação/genética , Neoplasias da Glândula Tireoide/patologiaRESUMO
Thyroid gland is an uncommon site of metastasis, and metastasis to the gland secondary to nasopharyngeal carcinoma is seldom seen. We were only able to identify eight reported cases in the literature. A 61-year-old man, diagnosed case of nasopharyngeal cancer-second primary ( first primary-oropharynx), was found to have a thyroid nodule on routine follow-up positron emission tomography-computed tomography (PET-CT) scan. There was no evidence of metastases at any other sites. The thyroid nodule was confirmed as metastatic carcinoma by fine needle aspiration cytology. He was treated with multimodal treatment comprising of surgery followed by reirradiation with concurrent chemotherapy. Subsequently, at the first follow-up (2 months after completion of all treatment), the patient remained asymptomatic, but the response assessment with PET-CT scan was suggestive of lung metastases with no evidence of locoregional disease. Although thyroid parenchymal metastasis is an uncommon occurrence and signifies a poor prognosis, in appropriately selected patients, aggressive therapy with reirradiation and chemotherapy may improve local control and quality of life.
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Decreased expression of CD3-ζ chain, an adaptor protein associated with T-cell signalling, is well documented in patients with oral cancer, but the mechanistic justifications are fragmentary. Previous studies in patients with oral cancer have shown that decreased expression of CD3-ζ chain was associated with decreased responsiveness of T cells. Tumours are known to induce localized as well as systemic immune suppression. This study provides evidence that oral tumour-derived factors promote immune suppression by down-regulating CD3-ζ chain expression. 2'5'-Oligoadenylate synthetase 2 (OAS2) was identified by the proteomic approach and our results established a causative link between CD3-ζ chain down-regulation and OAS2 stimulation. The surrogate situation was established by over-expressing OAS2 in a HEK293 cell line and cell-free supernatant was collected. These supernatants when incubated with T cells resulted in down-regulation of CD3-ζ chain, which shows that the secreted OAS2 is capable of regulating CD3-ζ chain expression. Incubation of T cells with cell-free supernatants of oral tumours or recombinant human OAS2 (rh-OAS2) induced caspase-3 activation, which resulted in CD3-ζ chain down-regulation. Caspase-3 inhibition/down-regulation using pharmacological inhibitor or small interfering RNA restored down-regulated CD3-ζ chain expression in T cells induced by cell-free tumour supernatant or rh-OAS2. Collectively these results show that OAS2 leads to impairment in CD3-ζ chain expression, so offering an explanation that might be applicable to the CD3-ζ chain deficiency observed in cancer and diverse disease conditions.
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2',5'-Oligoadenilato Sintetase/metabolismo , Complexo CD3/metabolismo , Caspase 3/metabolismo , Linfócitos do Interstício Tumoral/enzimologia , Neoplasias Bucais/enzimologia , Linfócitos T/enzimologia , 2',5'-Oligoadenilato Sintetase/genética , Complexo CD3/imunologia , Estudos de Casos e Controles , Caspase 3/genética , Linhagem Celular Tumoral , Regulação para Baixo , Ativação Enzimática , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Bucais/genética , Neoplasias Bucais/imunologia , Neoplasias Bucais/patologia , Comunicação Parácrina , Proteômica/métodos , Interferência de RNA , Proteínas Recombinantes/metabolismo , Transdução de Sinais , Linfócitos T/imunologia , Fatores de Tempo , Transfecção , Células Tumorais CultivadasRESUMO
BACKGROUND AND OBJECTIVES: Certain tumor-related factors like thickness increases the risk of nodal metastasis and may affect survival in patients with oral tongue cancers. The objective of this study is to identify those tumor-related prognostic predictors that can potentially influence decision for adjuvant radiotherapy. METHODS: A retrospective review of all patients with oral tongue cancers treated primarily by surgery at Tata Memorial Hospital between January 2007 and June 2010. The demographic and commonly reported histopathological features were analyzed for their influence on disease free and overall survival. RESULTS: Five hundred eighty-six patients were eligible for the study, of which 416 were males and 117 were females. Follow-up details were available for 498 (85%) patients with a median follow-up of 18 months and mean follow-up of 22 months. There were 302 patients who were alive and disease free at the last follow-up. This group had a mean follow-up of 27 months and median follow-up of 27.5 months. Disease recurrences during follow-up were observed in 184 (31%) patients. Sixty-one patients died subsequently. Perineural invasion significantly affected disease free survival (DFS). A tumor thickness of more than 11 mm significantly affected the overall survival (OS). CONCLUSION: Other than nodal metastasis, tumor-related factors like thickness and perineural invasion are adverse prognostic factors and can influence survival. These patients, especially in case of early stage cancers, may potentially benefit from postoperative adjuvant radiotherapy. LEVEL OF EVIDENCE: 2b.
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Carcinoma de Células Escamosas/cirurgia , Neoplasias da Língua/cirurgia , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias da Língua/mortalidade , Neoplasias da Língua/patologiaRESUMO
Oral carcinoma is a common disease that poses challenges in treatment management, especially for advanced cases. Adjuvant therapies, such as radiation and chemoradiation therapy, are typically used for advanced oral cancer patients. However, there is uncertainty regarding the use of adjuvant therapy for early-stage patients with certain soft histological parameters. The UICC manual of clinical oncology suggests that adjuvant therapy for such parameters is desirable but not essential. These parameters include perineural invasion, lymphovascular invasion, single nodal positivity, and patterns of invasion, which complicate the decision-making process for including adjuvant therapy. This review aims to provide evidence-based literature for effectively managing this patient group and developing treatment protocols based on current evidence.
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Neoplasias Bucais , Humanos , Neoplasias Bucais/terapia , Fatores de Risco , Consenso , Quimioterapia Adjuvante/métodosRESUMO
Parathyroid pathologies are suspected based on the biochemical alterations and clinical manifestations, and the predominant roles of imaging in primary hyperparathyroidism are localisation of tumour within parathyroid glands, surgical planning, and to look for any ectopic parathyroid tissue in the setting of recurrent disease. This article provides a comprehensive review of embryology and anatomical variations of parathyroid glands and their clinical relevance, surgical anatomy of parathyroid glands, differentiation between multiglandular parathyroid disease, solitary adenoma, atypical parathyroid tumour, and parathyroid carcinoma. The roles, advantages and limitations of ultrasound, four-dimensional computed tomography (4DCT), radiolabelled technetium-99 (99mTc) sestamibi or dual tracer 99mTc pertechnetate and 99mTc-sestamibi with or without single photon emission computed tomography (SPECT) or SPECT/CT, dynamic enhanced magnetic resonance imaging (4DMRI), and fluoro-choline positron emission tomography (18F-FCH PET) or [11C] Methionine (11C -MET) PET in the management of parathyroid lesions have been extensively discussed in this article. The role of fluorodeoxyglucose PET (FDG-PET) has also been elucidated in this article. Management guidelines for parathyroid carcinoma proposed by the American Society of Clinical Oncology (ASCO) have also been described. An algorithm for management of parathyroid lesions has been provided at the end to serve as a quick reference guide for radiologists, clinicians and surgeons.
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Thyroid cancer is the most common head and neck cancer (HNC) in the world. In this article, we comprehensively cover baseline, posttreatment, and follow-up imaging recommendations for thyroid carcinomas along with the eighth edition of the tumor, node, metastasis (TNM) staging system proposed by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC). We include characterization and risk stratification of thyroid nodules on ultrasound (US) proposed by various international bodies. Management guidelines (depending upon the type of thyroid carcinoma) based on the international consensus recommendations (mainly by the American Thyroid Association) are also extensively covered in this article, including the role of a radioiodine scan. The management of recurrent disease is also briefly elucidated in this article. In addition, we cover the risk factors and etiopathogenesis of thyroid carcinoma along with the non-imaging diagnostic workup essential for thyroid carcinoma management, including the significance of genetic mutations. US is the diagnostic imaging modality of choice, with US-guided fine needle aspiration (FNA) being the procedure of choice for tissue diagnosis. The roles of computed tomography (CT), magnetic resonance imaging (MRI), and fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT) in thyroid carcinoma staging are also specified. Through this article, we aim to provide a comprehensive reference guide for the radiologists and the clinicians in the pursuit of optimal care for patients with thyroid carcinoma.
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AIM OF THE STUDY: We previously reported a survival benefit of elective neck dissection (END) over therapeutic neck dissection (TND) in patients with clinically node-negative early-stage oral cancer. We now report the results of the second question in the same study addressing the impact of adding neck ultrasound to physical examination during follow-up on outcomes. METHODS: Patients with lateralized T1/T2 oral squamous cell carcinoma (SCC) were randomized to END or TND and to follow-up with physical-examination plus neck ultrasound (PE+US) versus physical-examination (PE). The primary endpoint was overall survival (OS). RESULTS: Between January 2004 and June 2014, 596 patients were enrolled. This is an intention to treat analysis of 592 analysable patients, of whom 295 were allocated to PE+US and 297 to PE with a median follow-up of 77.47 months (interquartile range (IQR) 54.51-126.48). There was no significant difference (unadjusted hazard ratio [HR], 0.92, 95% CI, 0.71-1.20, p = 0.54) in 5-year OS between PE+US (70.8%, 95% CI, 65.51-76.09) and PE (67.3%, 95% CI, 61.81-72.79). Among 131 patients with neck node relapse as the first event, the median time to relapse detection was 4.85 (IQR 2.33-9.60) and 7.62 (IQR 3.22-9.86) months in PE+US and PE arms, respectively. The N stage in the PE+US arm was N1 33.8%, N2a 7.4%, N2b/c 44.1% and N3 14.7% while in PE was N1 28.6%, N2a 9.5%, N2b/c 39.7%, N3 20.6% and unknown 1.6%. CONCLUSION: Adding neck ultrasound to physical examination during follow-up detects nodal relapses earlier but does not improve overall survival.
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Carcinoma de Células Escamosas , Neoplasias Bucais , Esvaziamento Cervical , Exame Físico , Ultrassonografia , Humanos , Masculino , Feminino , Neoplasias Bucais/patologia , Neoplasias Bucais/mortalidade , Neoplasias Bucais/diagnóstico por imagem , Neoplasias Bucais/terapia , Neoplasias Bucais/cirurgia , Pessoa de Meia-Idade , Ultrassonografia/métodos , Idoso , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Estadiamento de Neoplasias , Seguimentos , Resultado do TratamentoRESUMO
OBJECTIVES: To evaluate the prognostic role of the lymph node ratio (LNR; ratio of total positive nodes to total dissected nodes) in oral squamous cell carcinoma (OSCC) as compared to pN staging with an aim to provide an optimal cut-off value. METHODS: 1,408 OSCC previously untreated patients who underwent treatment (surgery + neck dissection + adjuvant treatment). LNR sensitivity with respect to survival was calculated using receiver operating characteristic (ROC) curves and Cox regression method. LNR and TNM staging variables were subjected to multivariate analysis. RESULTS: LNR (0.088) showed significant association with survival outcomes. For patients with LNR ≤0.088, the OS, DFS, local control, regional control and distant metastasis rates were 64%, 70%, and 89%; for LNR >0.088 it was 22%, 19%, and 52%, respectively (P < 0.001). On multivariate analysis LNR of 0.088 was seen to be an independent prognostic factor for 5-year regional control (p, hazard ratio [95% confidence interval]; 0.044, 2.016 (1.019-3.990), DFS, 0.032, 1.858 (1.054-3.276), and OS, 0.040, 1.195 (1.033-1.144). On multivariate analysis LNR categorization showed a statistically significant [0.032, 1.858, (1.054-3.276)] advantage over pN staging [0.527, 1.208 (1.054-3.276)] in predicting survival. CONCLUSIONS: LNR is a better prognostic marker than the current N staging of TNM classification.
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Carcinoma de Células Escamosas/mortalidade , Linfonodos/patologia , Neoplasias Bucais/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
BACKGROUND: India has one of the highest incidences of oral cancer and accounts for about 30% of all new cases annually. A high prevalence of smokeless tobacco use has led to an increasing incidence, which in combination with delayed presentation has made oral cancer a major health problem in India. Limited access to cancer care, relative lack of trained healthcare providers and financial resources are some of the challenges to the management of oral cancer in India despite improvements in diagnostic techniques and management strategies. METHODS: We reviewed the literature pertaining to the epidemiology, aetiopathogenesis, pre-malignancy, tumour progression, management of the primary site, mandible, neck lymph node metastases, reconstruction options and screening of oral cancer. The parameters evaluated were overall survival, disease-free survival, recurrence and loco-regional control. RESULTS: Nine studies on surgical intervention were reviewed. There were 23 studies on the management of chemotherapy and 30 trials analysing radiotherapy as an intervention. CONCLUSION: India has one of the highest incidences of oral cancer and delayed stage presentation is common. Surgery remains the treatment of choice and adjuvant treatment is recommended in high-risk patients. Elective neck dissection is warranted in clinically lymph node-negative neck for patients with thick tumours, imaging-suspected lymph nodes and those who may not have a reliable follow-up. Functional outcomes and treatment-related morbidity needs to be considered, and reconstruction with free tissue transfer provides the best results.
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Neoplasias Bucais/terapia , Detecção Precoce de Câncer , Humanos , Índia/epidemiologia , Metástase Linfática , Neoplasias Bucais/epidemiologia , Neoplasias Bucais/etiologia , Neoplasias Bucais/patologiaRESUMO
Background: Accurate neck staging is essential for performing appropriate surgery and avoiding undue morbidity in thyroid cancer. The modality of choice for evaluation is ultrasonography (US), which has limitations, particularly in the central compartment, that can be overcome by adding a computed tomography (CT). Methods: A total of 314 nodal levels were analyzed in 43 patients with CT, and US; evaluations were done between January 2013 and November 2015. The images were reviewed by two radiologists independently who were blinded to histopathological outcomes. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy of US, CT, and US + CT were calculated using histology as the gold standard. Results: The overall sensitivity, specificity, PPV, and NPV for US, CT, and US + CT were 53.9%, 88.8%, 74.1%, and 76.4%; 81.2%, 68.0%, 60.1%, and 85.9%; and 84.6%, 66.0%, 59.6%, and 87.8%, respectively. The overall accuracy of the US was 75.80%, the CT scan was 72.93%, and the US + CT scan was 72.93%. For the lateral compartment, the sensitivity, specificity, PPV, and NPV for the US, CT, and US + CT were 56.6%, 91.4%, 77.1%, and 80.5%; 80.7%, 70.6%, 58.3%, and 87.8%; and 84.3%, 68.7%, 57.9%, and 89.6%, respectively. The accuracy of the US was 79.67%, the CT scan was 73.98%, and the US + CT scan was 73.98% for the lateral compartment. For the central compartment, the sensitivity, specificity, PPV, and NPV for the US, CT, and US + CT were 47.1%, 76.5%, 66.7%, and 59.1%; 82.4%, 55.9%, 65.1%, and 76.0%; and 85.3%, 52.9%, 64.4%, and 78.3%, respectively. The accuracy of the US was 61.76%, the CT scan was 69.12%, and the US + CT scan was 69.12% for the central compartment. Conclusions: This study demonstrated that CT has higher sensitivity in detecting nodal metastasis; however, its role is complementary to US due to low specificity.
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Occult lymph-node metastasis is a crucial predictor of tongue cancer mortality, with an unmet need to understand the underlying mechanism. Our immunohistochemical and real-time PCR analysis of 208 tongue tumors show overexpression of Matrix Metalloproteinase, MMP10, in 86% of node-positive tongue tumors (n = 79; p < 0.00001). Additionally, global profiling for non-coding RNAs associated with node-positive tumors reveals that of the 11 significantly de-regulated miRNAs, miR-944 negatively regulates MMP10 by targeting its 3'-UTR. We demonstrate that proliferation, migration, and invasion of tongue cancer cells are suppressed by MMP10 knockdown or miR-944 overexpression. Further, we show that depletion of MMP10 prevents nodal metastases using an orthotopic tongue cancer mice model. In contrast, overexpression of MMP10 leads to opposite effects upregulating epithelial-mesenchymal-transition, mediated by a tyrosine kinase gene, AXL, to promote nodal and distant metastasis in vivo. Strikingly, AXL expression is essential and sufficient to mediate the functional consequence of MMP10 overexpression. Consistent with our findings, TCGA-HNSC data suggests overexpression of MMP10 or AXL positively correlates with poor survival of the patients. In conclusion, our results establish that the miR-944/MMP10/AXL- axis underlies lymph node metastases with potential therapeutic intervention and prediction of nodal metastases in tongue cancer patients.