Tumor thickness as an independent risk factor of early recurrence in oral cavity squamous cell carcinoma.

The aim is to determine if tumor thickness is a risk factor related to the development of early recurrences in surgically treated oral cavity squamous cell carcinoma (SCC). Retrospective cohort study conducted at Instituto do Câncer do Estado de São Paulo (ICESP). Fifty-seven patients with oral cavity SCC (excluding lip tumors and patients previously submitted to any treatment) were analyzed regarding the occurrence of an early disease progression (locoregional or distant metastasis) within the first 12 months after initial treatment. Tumor thickness and other histological characteristics related to the development of recurrence up to 1 year after treatment were tested. Results demonstrated that tumor thickness greater than 10 mm (P = 0.034), as well as angiolymphatic invasion (P = 0.001), perineural invasion (P = 0.041) and lymph-node metastasis (P = 0.021) was associated with a worse 12-month disease-free survival (Log-Rank test). In multivariate analysis, tumor thickness greater than 10 mm emerged as an independent risk factor for early recurrence in oral cavity tumors (HR = 3.4, 95% CI: 1.005-11.690; P = 0.049--Cox regression). Post-operative radiotherapy seems to be a protective factor for early recurrences in patients with tumor thickness greater than 10 mm (P = 0.017--Log-Rank test; HR = 0.32, 95% CI: 0.12-0.87, P = 0.026--Cox regression). The results of the present research suggest that tumor thickness greater than 10 mm may be an independent adverse factor for early progression of surgically treated oral cavity SCC. Adjuvant therapies, in particular post-operative radiotherapy, should be advocated in this group of patients, regardless of the co-existence of other well-described histological risk factors.

Incidental Node Metastasis as an Independent Factor of Worse Disease-Free Survival in Patients with Papillary Thyroid Carcinoma.

INTRODUCTION: Papillary thyroid carcinoma (PTC) have high node metastasis rates. Occasionally after thyroidectomy, the pathological report reveals node metastasis unintentionally resected. The present study aimed to evaluate the prognosis of these patients. METHODS: A retrospective cohort of patients submitted to thyroidectomy with or without central compartment neck dissection (CCND) due to PTC with a minimum follow-up of five years. RESULTS: A total of 698 patients were included: 320 Nx, 264 pN0-incidental, 37 pN1a-incidental, 32 pN0-CCND and 45 pN1a-CCND. Patients with node metastasis were younger, had larger tumors, higher rates of microscopic extra-thyroidal extension, and angiolymphatic invasion and most received radioiodine therapy. Treatment failure was higher in patients pN1a-incidental and pN1a-CCND (32% and 16%, respectively; p < 0.001-Chi-square test). Disease-free survival (DFS) was lower in patients pN1a-incidental compared to patients Nx and pN0-incidental (p < 0.001 vs. Nx and pN0-incidental and p = 0.005 vs. pN0-CCND) but similar when compared to patients pN1a-CCND (p = 0.091)-Log-Rank test. Multivariate analysis demonstrated as independent risk factors: pT4a (HR = 5.524; 95%CI: 1.380-22.113; p = 0.016), pN1a-incidental (HR = 3.691; 95%CI: 1.556-8.755; p = 0.003), microscopic extra-thyroidal extension (HR = 2.560; 95%CI: 1.303-5.030; p = 0.006) and angiolymphatic invasion (HR = 2.240; 95%CI: 1.077-4.510; p = 0.030). CONCLUSION: Patients that were pN1a-incidental were independently associated with lower DFS.

Impact of the COVID-19 Pandemic on Brazilian Head and Neck Surgery Centers.

OBJECTIVE: The outbreak of the COVID-19 pandemic had a considerable impact on the healthcare access, treatment, and follow-up of oncologic patients. The aim of this study was to evaluate how the COVID-19 pandemic has affected consultation and follow-up demand as well as treatment volume at Brazilian Head and Neck Surgery centers. METHODS: An anonymous online questionnaire was used for collection of data across all Brazilian Head and Neck Surgery Centers across a 3-month period (April‒June 2021). This information included the characteristics of each center, and the perceived self-reported impact of the COVID-19 pandemic on academic activities, residency training, and the diagnosis, treatment, and follow-up of patients with Head and Neck diseases between 2019 and 2020. RESULTS: The response rate across the 40 registered Brazilian Head and Neck Surgery Centers was 47.5% (n=19). The data showed a significant reduction in the total number of consultations (24.8%) and number of attending patients (20.2%) between 2019 and 2020. The total number of diagnostic exams (31.6%) and surgical procedures (13.0%) conducted over this period also decreased significantly. CONCLUSIONS: The COVID-19 pandemic had a significant national impact on Brazilian Head and Neck Surgery Centers. Future studies should examine the long-term effects of the pandemic on cancer treatment. LEVEL OF EVIDENCE: Evidence from a single descriptive study.

Profile of MicroRNAs Associated with Death Due to Disease Progression in Metastatic Papillary Thyroid Carcinoma Patients.

Papillary thyroid carcinoma (PTC) is the most common neoplasm of the endocrine system and has an excellent long-term prognosis, with low rates of distant metastatic disease. Although infrequent, there are cases of deaths directly related to PTC, especially in patients with metastatic disease, and the factors that could be associated with this unfavorable outcome remain a major challenge in clinical practice. Recently, research into genetic factors associated with PTC has gained ground, especially mutations in the TERT promoter and BRAF gene. However, the role of microRNAs remains poorly studied, especially in those patients who have an unfavorable outcome at follow-up. This paper aims to evaluate molecular markers related to the different pathological processes of PTC, as well as the histological characteristics of the neoplasm, and to compare this profile with prognosis and death from the disease using an analysis of patients treated for metastatic disease in a single tertiary cancer center. Evaluation of microRNA expression in paraffin-embedded tumor specimens was carried out by quantitative PCR using the TaqMan® Low Density Array (TLDA) system. Metastatic patients who died from progression of PTC had higher expressions of miR-101-3p, miR-17-5p, and miR-191-5p when compared to patients with stable metastatic disease. These findings are of great importance but should be considered as preliminary because of the small sample.

Risk factors associated with disease-specific mortality in papillary thyroid cancer patients with distant metastases.

PURPOSE: Papillary thyroid carcinoma (PTC) is among the most curable cancer types. Even though uncommon, some patients present distant metastatic disease at diagnosis or during the follow-up and most of them have long-term survival. However, there continues to be controversies regarding what clinicopathological features are associated with mortality in these patients. This paper evaluates the factors related to poor disease-specific survival (DSS) in patients with metastatic PTC. METHODS: A retrospective cohort study included PTC patients with distant metastasis from a tertiary public oncological center. Clinicopathological features, treatment modalities, and outcome were reviewed. RESULTS: Between 1986 and 2014, 108 patients were diagnosed with metastatic PTC. In the multivariate analysis male sex (HR = 2.65; 95%CI: 1.08-6.53; P = 0.033), radioiodine refractory disease (HR = 9.50; 95%CI: 1.23-73.38; P = 0.031) and metastasis at multiple sites (HR = 5.91; 95%CI: 1.80-19.32; P = 0.003) were independent risk factors for death in patients with metastatic PTC. CONCLUSION: Male patients with metastatic PTC, with radioiodine refractory disease and metastasis at multiple sites have a high risk of death.

Survival in differentiated thyroid carcinoma: Comparison between the 7th and 8th editions of the AJCC/UICC TNM staging system and the ATA initial risk stratification system.

BACKGROUND: The AJCC/UICC TNM staging system evaluates the risk of death from cancer. Its 8th edition aimed to increase its accuracy. In turn, the American Thyroid Association proposed an initial risk stratification system (IRSS) focusing on the risk of recurrence in differentiated thyroid carcinoma. The present study intended to analyze their prediction abilities. METHODS: Six hundred and eighty-five consecutive surgical patients (mean follow-up 71.6 months) were staged. Correlations with disease-free survival (DFS) and overall survival (OS) were carried out. RESULTS: IRSS was discriminative for DFS but not for OS. Applying TNM 8th, 36.9% of the cohort was downstaged. Their DFS was shorter, compared with other patients in the same stage, but with no impact on OS. However, all those who died of the disease had been downstaged. CONCLUSIONS: IRSS was more effective to predict DFS, but not OS. TNM 8th was more appropriate for OS analysis than TNM 7th and IRSS.

Impact of the COVID-19 Pandemic on Brazilian Head and Neck Surgery Centers

Abstract Objective The outbreak of the COVID-19 pandemic had a considerable impact on the healthcare access, treatment, and follow-up of oncologic patients. The aim of this study was to evaluate how the COVID-19 pandemic has affected consultation and follow-up demand as well as treatment volume at Brazilian Head and Neck Surgery centers. Methods An anonymous online questionnaire was used for collection of data across all Brazilian Head and Neck Surgery Centers across a 3-month period (April‒June 2021). This information included the characteristics of each center, and the perceived self-reported impact of the COVID-19 pandemic on academic activities, residency training, and the diagnosis, treatment, and follow-up of patients with Head and Neck diseases between 2019 and 2020. Results The response rate across the 40 registered Brazilian Head and Neck Surgery Centers was 47.5% (n = 19). The data showed a significant reduction in the total number of consultations (24.8%) and number of attending patients (20.2%) between 2019 and 2020. The total number of diagnostic exams (31.6%) and surgical procedures (13.0%) conducted over this period also decreased significantly. Conclusions The COVID-19 pandemic had a significant national impact on Brazilian Head and Neck Surgery Centers. Future studies should examine the long-term effects of the pandemic on cancer treatment. Level of evidence Evidence from a single descriptive study.

Expression of membrane type 1 matrix metalloproteinase in medullary thyroid carcinoma: prognostic implications.

BACKGROUND: Clinical and pathologic examinations cannot always provide a prognosis for patients with medullary thyroid carcinoma. Membrane type 1 matrix metalloproteinase (MT1-MMP) can act directly on carcinogenesis and takes part in 1 of the processes of metalloproteinase 2 activation, an enzyme related to prognostic impairment of patients with such tumor. METHODS: Thirty-five patients who were submitted to surgery were followed up for an average of 74 months. Postoperative and final medical conditions were characterized for comparison with MT1-MMP immunostainings, performed in surgical paraffin blocks. A value of p < .05 was considered statistically significant. RESULTS: Proposed index (association of proportion and intensity of immunostaining) and proportion of immunostained cells in primary specimens were correlated with cure or persistence after initial operations (p = .0216 and p = .0098, respectively). CONCLUSION: MT1-MMP immunostaining in primary tumor specimens is a new and complementary prognostic predictor in patients with medullary thyroid carcinomas.

Ratio of metalloproteinase 2 to tissue inhibitor of metalloproteinase 2 in medullary thyroid carcinoma.

OBJECTIVES: To develop an index for the ratio of metalloproteinase 2 (MMP-2) to its tissue inhibitor (TIMP-2) in immunostained medullary thyroid carcinoma specimens and to correlate it with clinical and pathologic prognostic factors. Metalloproteinases, enzymes related to the degradation of the extracellular matrix, take part in carcinogenesis and have been associated with the prognosis of neoplasias. Nevertheless, medullary carcinoma is rarely considered in research analysis. Researchers tend to favor the ratio of enzymes to their inhibitors over the absolute concentrations of these enzymes. DESIGN: Retrospective study of surgical samples. SETTING: Head and Neck Surgery and Endocrinology Departments, Universidade de São Paulo Medical School Hospital. PATIENTS: Surgical specimens from 33 patients who had been observed for a mean of 76.8 months (range, 4-201 months) were immunohistochemically stained for MMP-2 and TIMP-2. Only patients whose clinical and pathologic data were complete and whose specimens were preserved were included in the study. MAIN OUTCOME MEASURES: The ratio between the expressions of MMP-2 and TIMP-2 was based on a staining index (immunostaining extent and intensity) of each of the markers. RESULTS: Proportionally large expressions of TIMP-2 over MMP-2 correlated with low occurrences of positive findings on initial cervical examination for the presence of thyroid nodules and/or lymphadenopathy (P = .02) and cervical lymph node metastases (P < .001), conditions correlated with prognosis. A correlation with cure at the end of follow-up (P = .01) was also observed. (P< .05 was considered statistically significant.) CONCLUSION: The ratio of MMP-2 to TIMP-2 expression is an additional and novel prognostic predictor of the outcome of medullary carcinoma treated surgically.

Espessura tumoral como fator de risco independente para a recorrência precoce em portadores de carcinomas espinocelulares da cavidade oral / Tumor thickness as an independent risk factor of early recurrence in oral cavity squamous cell carcinoma

Introdução: A espessura tumoral é reconhecidamente um fator de risco para a presença de metástases ocultas e para menor sobrevivência em carcinoma espinocelular da cavidade oral, porém o tratamento adjuvante desses pacientes não foi alterado. O intervalo livre de doença é outro fator associado a pior prognóstico, e é sabido que as recorrências precoces também diminuem a sobrevivência desses pacientes. Objetivo: Determinar se a espessura tumoral é um fator de risco para recorrências precoces em portadores de carcinomas espinocelulars de cavidade oral operados. Pacientes e Métodos: Estudo de coorte retrospectivo conduzido no Instituto do Câncer do Estado de São Paulo (ICESP) com 57 pacientes portadores de carcinomas espinocelulars de boca, exceto lábios, e virgens de tratamento prévio. Analisou-se o desenvolvimento de recorrência de doença (locorregional ou a distância) nos primeiros 12 meses após o tratamento inicial. Os aspectos histopatológicos dos espécimes foram analisados. Resultados: Espessura tumoral maior do que 10 mm (p=0,034), invasão angiolinfática (p=0,001), invasão perineural (p=0,041) e metástases linfonodais cervicais (p=0,021) apresentaram associação com menor sobrevivência livre de doença no primeiro ano após o tratamento (teste de LogRank). À análise multivariada, a espessura tumoral maior que 10 mm foi identificada como um fator de risco independente de progressão inicial da doença. A radioterapia pós-operatória pareceu representar um fator protetor contra a progressão inicial dos tumores com espessura superior a 10 mm. Conclusão: A espessura tumoral superiores a 10 mm representa um fator de risco independente para a progressão precoce do carcinoma espinocelular de cavidade oral cirurgicamente tratado. Terapias adjuvantes, especialmente a radioterapia, devem ser consideradas, a despeito da coexistência de outros fatores histológicos de risco bem estabelecidos.

Introduction: Tumor thickness has been recognized as a risky factor for occult regional metastasis and survival in oral squamous cell carcinoma. Nevertheless, the adjuvant treatment of these neoplasms did not change regarding the thickness of the tumor. Disease-free interval is another factor associated with prognosis in head and neck cancer, and, it is known that early recurrences adversely affect survival. Objective: To determine if tumor thickness is a risk factor related to the development of early recurrences in surgically treated oral cavity squamous cell carcinoma. Methods: Retrospective cohort study conducted at Instituto do Câncer do Estado de São Paulo (ICESP). Results: Fifty-seven patients with oral cavity squamous cell carcinoma (excluding lip tumors and patients previously submitted to any treatment) were analyzed regarding the occurrence of an early disease progression (locoregional or distant metastasis) within the first 12 months after initial treatment. Tumor thickness and other histological characteristics related to the development of recurrence up to one year after treatment were tested. Results demonstrated that tumor thickness greater than 10 mm (P=0.034), as well as angiolymphatic invasion (P=0.001), perineural invasion (P=0.041) and lymph node metastasis (P=0.021) were associated with a worse 12-month disease-free survival (Log-Rank test). In multivariate analysis, tumor thickness greater than 10 mm emerged as an independent risk factor for early recurrence in oral cavity tumors (HR=3.4, CI95%: 1.005-11.690; P=0.049 - Cox regression). Post-operative radiotherapy seems to be a protective factor for early recurrences in patients with tumor thickness greater than 10 mm (P=0.017 - Log-Rank test; HR=0.32, CI95%: 0.12-0.87, P=0.026 - Cox regression). Conclusion: The results of the present research suggest that tumor thickness greater than 10 mm may be an independent adverse factor for early progression of surgically treated oral cavity squamous cell carcinoma. Adjuvant therapies, in particular post-operative radiotherapy, should be advocated in this group of patients, regardless of the co-existence of other well described histological risk factors.

Expressão das metaloproteinases MMP-2, MT1-MMP e TIMP-2 e aspectos climicopatológicos no cardinoma medular da glândula tireóide: implicações prognósticas / Expression of matriz metalloproteinases MMP-2, TIMP-2 e MT1-MMp and clinicopathologic aspects in medullary thyroid carcinoma

Metaloproteinases (MMP) são enzimas proteolíticas, fundamentais à carcinogênese. Evoluções de 37 pacientes operados por carcinomas medulares da tireóide foram comparadas com dados clinicopatológicos e expressões imuno-histoquímicas de MMP-2, MT1-MMP e TIMP-2 em seus espécimes neoplásicos. Condições clínicas finais foram correlacionadas com os aspectos clinicopatológicos: exame físico cervical positivo, sintomas sistêmicos, diâmetro tumoral, extensão neoplásica para a cápsula tireóidea, extensão tumoral para tecidos adjacentes, invasão vascular, metástases cervicais, estádio TNM, evidências de doenças cervical e/ou a distância. Expressões de MMP-2 e MT1-MMP foram correlacionadas à evolução clínica e maior proporção de TIMP-2, em relação à MMP-2, correlacionou-se a benefícios prognósticos / Metalloproteinases (MMP) are proteolytic enzymes, fundamental to carcinogenesis. Outcome of 37 patients operated on due to medullary thyroid carcinomas were compared to clinicopathologic data and immunohistochemistry expression of MMP-2, MT1-MMP and TIMP-2 in their neoplastic specimens. Final clinical conditions were related to the clinicopathologic aspects: clinical features, systemic symptoms, tumor size, tumor extension to thyroid capsule, tumor extension to adjacent tissues, vascular invasion, cervical metastases, TNM stage and evidences of disease in the neck and/or distant metastases. Expression of MMP-2 and MT1-MMP were related to outcome and greater proportion of TIMP-2, over MMP-2, was related to prognostic benefits...