The hidden curve behind COVID-19 outbreak: the impact of delay in treatment initiation in cancer patients and how to mitigate the additional risk of dying-the head and neck cancer model.

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.

Individualized risk assessment of distant metastases in oral cavity carcinoma: a validated predictive-score model.

BACKGROUND: We aimed to develop and validate a risk-scoring system for distant metastases (DMs) in oral cavity carcinoma (OCC). METHODS: Patients with OCC who were treated at 4 tertiary cancer institutions with curative surgery with or without postoperative radiation/chemoradiation therapy were randomly assigned to discovery or validation cohorts (3:2 ratio). Cases were staged on the basis of tumor, node, and metastasis staging according to the eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control guidelines. Predictors of DMs on multivariable analysis in the discovery cohort were used to develop a risk-score model and classify patients into risk groups. The utility of the risk classification was evaluated in the validation cohort. RESULTS: Overall, 2749 patients were analyzed. Predictors (risk score coefficient) of DMs in the discovery cohort were the following: pathological stage (p)T3-4 (0.4), pN+ (N1: 0.8; N2: 1.0; N3: 1.5), histologic grade (G) 3 (G3, 0.7), and lymphovascular invasion (0.4). The DM risk groups were defined by the sum of the following risk score coefficients: high (>1.7), intermediate (0.7-1.7), and standard risk (<0.7). The 5-year DM rates (high/intermediate/standard risk groups) were 30%/15%/4% in the discovery cohort (C-index = 0.79) and 35%/16%/5% in the validation cohort, respectively (C-index = 0.77; both P < .001). In the whole cohort, this predictive model showed excellent discriminative ability in predicting DMs without locoregional failure (29%/11%/1%), later (>2 year) DMs (11%/4%/2%), and DMs in patients treated with surgery (20%/12%/5%), postoperative radiation therapy (34%/17%/4%), and postoperative chemoradiation therapy (39%/18%/7%) (all P < .001). The 5-year overall survival rates in the overall cohort were 25%/51%/67% (P < .001). CONCLUSIONS: Patients at higher risk for DMs were identified by use of a predictive-score model for DMs that included pT3-4, pN1/2/3, G3, and lymphovascular invasion. Identified patients may be evaluated for individualized risk-adaptive treatment escalation and/or surveillance strategies.

Management of Older Patients with Head and Neck Cancer: A Comprehensive Review.

The projected increase in life expectancy over the next few decades is expected to result in a rise in age-related diseases, including cancer. Head and neck cancer (HNC) is a worldwide health problem with high rates of morbidity and mortality. In this report, we have critically reviewed the literature reporting the management of older patients with HNC. Older adults are more prone to complications and toxicities secondary to HNC treatment, especially those patients who are frail or have comorbidities. Thus, this population should be screened prior to treatment for such predispositions to maximize medical management of comorbidities. Chronologic age itself is not a reason for choosing less intensive treatment for older HNC patients. Whenever possible, also older patients should be treated according to the best standard of care, as nonstandard approaches may result in increased treatment failure rates and mortality. The treatment plan is best established by a multidisciplinary tumor board with shared decision-making with patients and family. Treatment modifications should be considered for those patients who have severe comorbidities, evidence of frailty (low performance status), or low performance status or those who refuse the recommendations of the tumor board.

Impact of the COVID-19 Pandemic on Physicians Working in the Head and Neck Field.

Background With the COVID-19 pandemic, the clinical practice of physicians who work in the head and neck field in Brazil dropped dramatically. The sustained impact of the pandemic is not known. Methods An anonymous online survey was distributed to Brazilian otolaryngologists, head and neck surgeons, medical and radiation oncologists, asking about their clinical practice in the third to fourth months of the pandemic. Results The survey was completed by 446 specialists. About 40% reported reduction of more than 75% in outpatient care. A reduction of 90% to 100% in airway endoscopies was reported by 50% of the responders, and the same rate of reduction regarding surgeries (pediatric or nasosinusal) was reported by 80% of them. Family income decreased by 50%, and the psychological burden on physicians was considerable. The availability of personal protective equipment and safety precautions were limited, especially in the public sector. Conclusion COVID-19 is still impacting the head and neck field, and safety concerns may hinder the prompt resumption of elective care.

Evaluation of lung function in patients submitted to total laryngectomy.

INTRODUCTION: The post-laryngectomy state is characterized by several alterations in lung function. A reliable estimation of lung function can be very useful in laryngectomees to prevent postoperative complications and to evaluate the results of the treatment. OBJECTIVE: Characterize the presence of respiratory functional disorders and the functional pattern of laryngectomees through the use of an extratracheal device. METHODS: This transversal study included 50 patients submitted to total laryngectomy at least 6 months prior to this investigation, as the treatment of choice for laryngeal cancer. RESULTS: 56% percent of the participants had altered breathing pattern, distributed as follows: 14 with obstructive pattern with no air trapping, 11 with obstructive pattern with air trapping and only 3 with restrictive pattern. On average, the diffusion decreased (74.3%) and airway resistance increased (121.7%) when compared to the expected average values for the Brazilian individuals. CONCLUSION: Most patients submitted to total laryngectomy present altered lung function, usually the obstructive type, frequently associated to a history of smoking.

Heparanase-2, syndecan-1, and extracellular matrix remodeling in colorectal carcinoma.

AIM: To propose a quantitative method to detect heparanase-2 (HPA2) and syndecan-1 (Syn-1) using immunohistochemistry in colorectal (colon and rectal) carcinomas compared with nonneoplastic tissues and evaluate the possible role of these molecules in tumor development and extracellular remodeling. METHODS: Cytoplasmic staining of HPA2 and Syn-1 was obtained by standard immunohistochemical reactions in 50 colorectal carcinoma and 20 nonneoplastic large bowels tissues. An image system was used to quantify the immunoexpression by digital computer-assisted method (Matos et al. 2006). The cutoff point for the immunohistochemistry variable was defined by sensibility and specificity curves. Statistical analysis was performed using SPSS version 13.0. RESULTS: HPA2 was over-expressed in colorectal cancer (131.1+/-24.9 o.u./microm) when compared with nonneoplastic tissues (27.9+/-12.2 o.u./microm) (P<0.0001). However, an opposite correlation was observed between Syn-1 and tumor presence, where colorectal tissues expressed lower Syn-1 proteoglycan compared with nonneoplastic tissues, respectively (39.2+/-17.8 o.u./microm) and (102.2+/-25.2 o.u./microm) (P<0.0001). CONCLUSION: A methodology with high sensitivity and specificity is proposed with a cutoff value for HPA2 and Syn-1 in the immunohistochemistry assay to define the presence of tumor. It was demonstrated for the first time in the literature that HPA2 is over-expressed in colorectal carcinoma tissues compared with nonneoplastic tissues. HPA2 over-expression could be possibly related to Syn-1 shedding despite the fact that HPA2 does not present enzymatic activity as HPA1.

Deaths related to differentiated thyroid cancer: a rare but real event.

OBJECTIVE: The present study describes the clinical and tumor characteristics of patients that died from differentiated thyroid cancer and reports on the cause and circumstances of death in these cases. SUBJECTS AND METHODS: Retrospective analysis of all the differentiated thyroid cancer (DTC) related deaths at a single institution over a 5-year period, with a total of 33 patients. RESULTS: Most of the patients were female (63.6%), with a mean age at diagnosis of 58.2 years. The most common histologic type was papillary (66.7%) and 30.3% were follicular. The distribution according to the TNM classification was: 15.4% of T1; 7.7% T2; 38.4% T3; 19.2% of T4a and 19.2% of T4b. Forty-four percent of cases were N0; 20% N1a and 36.6% of N1b. Twelve patients were considered non-responsive to radioiodine. Only one of the patients did not have distant metastases. The most common metastatic site was the lung in 69.7%. The majority of deaths were due to pulmonary complications related to lung metastases (17 patients, 51.5%), followed by post-operative complications in 5 cases, neurological disease progression in 3 cases, local invasion and airway obstruction in one patient. Median survival between diagnosis and death was reached in 49 months while between disease progression and death it was at 22 months. CONCLUSION: Mortality from DTC is extremely rare but persists, and the main causes of death derive from distant metastasis, especially respiratory failure due to lung metastasis. Once disease progression is established, median survival was only 22 months.

Surgical treatment for thyroid carcinoma: retrospective study with 811 patients in a Brazilian tertiary hospital.

Objective: The aim of the present study was to describe the epidemiologic data, histological type, treatment and follow-up of the 811 patients treated for thyroid cancer in Instituto do Câncer do Estado de São Paulo (ICESP) over 5 years. Materials and methods: Retrospective analyses of electronic chart information. Results: There were 679 cases (83.7%) of papillary thyroid cancer, 61 (7.5%) of follicular carcinoma, 54 (6.7%) of medullary carcinoma, 11 (1.4%) of poorly differentiated carcinoma and 6 of anaplastic carcinoma (0.7%). The majority of patients were female (82.2%), and the mean age was 50.5 ± 15 years. Two hundred forty-two patients had disease persistence or recurrence. At the last follow-up, 629 (77.6%) patients were alive and disease free, 141 (17.4%) were alive with disease, and 41 (5.1%) were deceased, with 37 deaths related to thyroid cancer. Conclusion: This study was able to outline the profile, disease type and evolution of patients treated for thyroid cancer at a single tertiary hospital.

Impact of the COVID-19 Pandemic on Physicians Working in the Head and Neck Field

Abstract Background With the COVID-19 pandemic, the clinical practice of physicians who work in the head and neck field in Brazil dropped dramatically. The sustained impact of the pandemic is not known. Methods An anonymous online survey was distributed to Brazilian otolaryngologists, head and neck surgeons, medical and radiation oncologists, asking about their clinical practice in the third to fourth months of the pandemic. Results The survey was completed by 446 specialists. About 40 % reported reduction of more than 75 % in outpatient care. A reduction of 90 % to 100 % in airway endoscopies was reported by 50 % of the responders, and the same rate of reduction regarding surgeries (pediatric or nasosinusal) was reported by 80 % of them. Family income decreased by 50 %, and the psychological burden on physicians was considerable. The availability of personal protective equipment and safety precautions were limited, especially in the public sector. Conclusion COVID-19 is still impacting the head and neck field, and safety concerns may hinder the prompt resumption of elective care.

Prevalence of human papillomavirus types and variants and p16(INK4a) expression in head and neck squamous cells carcinomas in São Paulo, Brazil.

BACKGROUND: Human papillomavirus (HPV) prevalence in head and neck squamous cell carcinomas (HNSCC) diverges geographically. The reliability of using p16(INK4a) expression as a marker of viral infection is controversial in HNSCC. We evaluated HPV types and HPV-16 variants prevalence, and p16(INK4a) expression in HNSCC specimens provided by two different Institutions in São Paulo. METHODS: HPV DNA from formalin-fixed specimens was accessed by Inno-LiPA, HPV-16 variants by PCR-sequencing, and p16(INK4a) protein levels by immunohistochemistry. RESULTS: Overall, HPV DNA was detected among 19.4 % of the specimens (36/186). Viral prevalence was higher in the oral cavity (25.0 %, 23/92) then in other anatomical sites (oropharynx 14,3 %, larynx 13.7 %) when samples from both Institutions were analyzed together. HPV prevalence was also higher in the oral cavity when samples from both Institutions were analyzed separately. HPV-16 was the most prevalent type identified in 69.5 % of the HPV positive smaples and specimens were assigned into Asian-American (57.2 %) or European (42.8 %) phylogenetic branches. High expression of p16(INK4a) was more common among HPV positive tumors. CONCLUSION: Our results support a role for HPV-16 in a subset of HNSCC.

Evaluation of lung function in patients submitted to total laryngectomy / Avaliação da função pulmonar em pacientes submetidos à laringectomia total

Abstract Introduction: The post-laryngectomy state is characterized by several alterations in lung function. A reliable estimation of lung function can be very useful in laryngectomees to prevent postoperative complications and to evaluate the results of the treatment. Objective: Characterize the presence of respiratory functional disorders and the functional pattern of laryngectomees through the use of an extratracheal device. Methods: This transversal study included 50 patients submitted to total laryngectomy at least 6 months prior to this investigation, as the treatment of choice for laryngeal cancer. Results: 56% percent of the participants had altered breathing pattern, distributed as follows: 14 with obstructive pattern with no air trapping, 11 with obstructive pattern with air trapping and only 3 with restrictive pattern. On average, the diffusion decreased (74.3%) and airway resistance increased (121.7%) when compared to the expected average values for the Brazilian individuals. Conclusion: Most patients submitted to total laryngectomy present altered lung function, usually the obstructive type, frequently associated to a history of smoking.

Resumo Introdução: A condição pós-laringectomia é caracterizada por várias alterações na função pulmonar. Uma estimativa confiável da função pulmonar pode ser muito útil em pacientes laringectomizados para prevenir complicações após as intervenções cirúrgicas e avaliar os resultados do tratamento. Objetivo: Caracterizar a presença de distúrbios funcionais respiratórios e o padrão funcional de pacientes laringectomizados através do uso de um dispositivo extratraqueal. Método: Estudo transversal que incluiu 50 pacientes submetidos à laringectomia total pelo menos seis meses antes desta investigação, como tratamento de escolha para o câncer de laringe. Resultados: Dos participantes, 56% apresentavam padrão respiratório alterado, assim distribuídos: 14 com padrão obstrutivo sem aprisionamento aéreo, 11 com padrão obstrutivo e aprisionamento aéreo e apenas três com padrão restritivo. Em média, verificou-se que a difusão encontrava-se diminuída (74,3%) e a resistência das vias aéreas aumentada (121,7%) em relação aos resultados esperados em brasileiros. Conclusão: A maioria dos pacientes submetidos à laringectomia total apresenta função pulmonar alterada, do tipo obstrutiva, quase sempre associada a história de tabagismo.

Deaths related to differentiated thyroid cancer: a rare but real event

ABSTRACT Objective The present study describes the clinical and tumor characteristics of patients that died from differentiated thyroid cancer and reports on the cause and circumstances of death in these cases. Subjects and methods Retrospective analysis of all the differentiated thyroid cancer (DTC) related deaths at a single institution over a 5-year period, with a total of 33 patients. Results Most of the patients were female (63.6%), with a mean age at diagnosis of 58.2 years. The most common histologic type was papillary (66.7%) and 30.3% were follicular. The distribution according to the TNM classification was: 15.4% of T1; 7.7% T2; 38.4% T3; 19.2% of T4a and 19.2% of T4b. Forty-four percent of cases were N0; 20% N1a and 36.6% of N1b. Twelve patients were considered non-responsive to radioiodine. Only one of the patients did not have distant metastases. The most common metastatic site was the lung in 69.7%. The majority of deaths were due to pulmonary complications related to lung metastases (17 patients, 51.5%), followed by post-operative complications in 5 cases, neurological disease progression in 3 cases, local invasion and airway obstruction in one patient. Median survival between diagnosis and death was reached in 49 months while between disease progression and death it was at 22 months. Conclusion Mortality from DTC is extremely rare but persists, and the main causes of death derive from distant metastasis, especially respiratory failure due to lung metastasis. Once disease progression is established, median survival was only 22 months.

Surgical treatment for thyroid carcinoma: retrospective study with 811 patients in a Brazilian tertiary hospital

ABSTRACT Objective The aim of the present study was to describe the epidemiologic data, histological type, treatment and follow-up of the 811 patients treated for thyroid cancer in Instituto do Câncer do Estado de São Paulo (ICESP) over 5 years. Materials and methods Retrospective analyses of electronic chart information. Results There were 679 cases (83.7%) of papillary thyroid cancer, 61 (7.5%) of follicular carcinoma, 54 (6.7%) of medullary carcinoma, 11 (1.4%) of poorly differentiated carcinoma and 6 of anaplastic carcinoma (0.7%). The majority of patients were female (82.2%), and the mean age was 50.5 ± 15 years. Two hundred forty-two patients had disease persistence or recurrence. At the last follow-up, 629 (77.6%) patients were alive and disease free, 141 (17.4%) were alive with disease, and 41 (5.1%) were deceased, with 37 deaths related to thyroid cancer. Conclusion This study was able to outline the profile, disease type and evolution of patients treated for thyroid cancer at a single tertiary hospital.

Glycosaminoglycan synthesis and shedding induced by growth factors are cell and compound specific.

The interactions between growth factors and sulphated glycosaminoglycans (GAG) have been extensively studied. The aim of this study is to investigate if growth factors would show specificity of action on the synthesis and shedding of sulphated GAG, using two different cell lines: endothelial and smooth muscle cells. The cells were grown in the presence or absence of growth factors: EGF, FGF2, VEGF121, VEGF165. Transfection assays were also performed using recombinant pcDNA3.1, containing VEGF165 cDNA. In order to analyse the different types of GAG the cells were metabolically labelled with [(35)S]-sulphate. At low doses, VEGF121 was the only growth factor able to increase both the synthesis and secretion of heparan sulphate (HS) in endothelial cells. Over expression of VEGF165 stimulated HS synthesis in both cells. The combined results showed that growth factors affect GAG synthesis in a cell specific and dose dependent manner.