Systemic therapies for salivary gland carcinomas: an overview of published clinical trials

Background: There is no consensus about effective systemic therapy for salivary gland carcinomas (sgcs). Our aim was summarized the clinical trials assessing the systemic therapies (ST) on sgcs.Material and Methods: Electronic searches were carried out through MEDLINE/pubmed, EMBASE, Scopus, Web of Science, and the Cochrane Library databases, and gray literature. Results: Seventeen different drugs were evaluated, and the most frequent histological subtype was adenoid cysticcarcinoma (n=195, 45.5%). Stable disease, observed in 11 ST, achieved the highest rate in adenoid cystic carcinoma treated with sunitinib. The highest complete (11.1%) and partial response (30.5%) rates were seen in androgen receptor-positive tumors treated with leuprorelin acetate. Conclusions: Despite all the advances in this field, there is yet no effective evidence-based regimen of ST, with all the clinical trials identified showing low rates of complete and partial responses. Further, translational studies are urgently required to characterize molecular targets and effective ST. (AU)

Cushing's syndrome due to ectopic adrenocorticotropin secretion by a parotid carcinoma

SUMMARY We report a rare case of Cushing's syndrome in a 37-year-old female who initially presented with localized acinic cell carcinoma of the parotid gland. In January 2014, she underwent a right parotidectomy with facial nerve preservation and adjuvant radiotherapy. In August 2018, she presented a histologically-proven local regional relapse. The patient was considered for salvage surgery with facial nerve sacrifice and remained with no evidence of disease. One year later the patient developed pulmonary dissemination and started to gain weight and developed facial plethora and acne on the face and upper trunk. In a physical examination, the patient presented moon face, buffalo hump, acne and stage 2 hypertension. Biochemical evaluation confirmed ACTH-dependent Cushing's syndrome. IHC for ACTH in the lung biopsy revealed strong positive staining for ACTH confirming a diagnosis of ectopic ACTH secretion by a metastatic parotid acinic cell carcinoma. Ketoconazole (600 mg/d) was started to treat the CS. In addition, as chemotherapy was initiated to treat the metastatic disease. After the fifth cycle of chemotherapy, ketoconazole was suspended and the patient remained in remission of CS for four months, when CS recurred. A unique feature of this case is related to the clinical CS relapse associated with disease progression, which needed prompt treatment with ketoconazole, resulting in a significant improvement in the patient's condition. Although rare, should be attentive for possible CS features in patients with high-grade salivary gland carcinomas, since the diagnosis of ectopic secretion of ACTH may significantly impact their management and outcomes.

Effect of the COVID-19 Pandemic on the Activity of Physicians Working in the Areas of Head and Neck Surgery and Otorhinolaryngology.

Introduction Coronavirus disease 2019 (COVID-19) is an acute infection caused by the new coronavirus (SARS-CoV-2) and it is highly transmissible, especially through respiratory droplets. To prepare the health system for the care of these patients also led to a restriction in the activity of several medical specialties. Physicians who work with patients affected by diseases of the head and neck region constitute one of the populations most vulnerable to COVID-19 and also most affected by the interruption of their professional activities. Objective The aim of the present study was to assess the impact of the COVID-19 pandemic on the practice of head and neck surgeons and otorhinolaryngologists in Brazil. Methods An anonymous online survey of voluntary participation was applied, containing 30 questions regarding demographic aspects, availability of personal protective equipment (PPE), and impact on the routine of head and neck surgeons and otorhinolaryngologists, as well as clinical oncologists and radiation oncologists who work with head and neck diseases. Results Seven hundred and twenty-nine answers were received in a period of 4 days, ∼ 40 days after the 1 st confirmed case in Brazil. With professionals working in public and private services, there was a high level of concerns with the disease and its consequences, limited availability of PPE and a significant decrease in the volume of specialized medical care. Conclusion The study demonstrated a direct impact of the COVID-19 pandemic on the clinical practice of specialties related to the treatment of patients with diseases of the head and neck region already in the beginning of the illness management in Brazil.

Lung Cancer and the COVID-19 pandemic: Recommendations from the Brazilian Thoracic Oncology Group.

New cases of the novel coronavirus disease 2019 (COVID-19), also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continue to rise worldwide following the declaration of a pandemic by the World Health Organization (WHO). The current pandemic has completely altered the workflow of health services worldwide. However, even during this critical period, patients with other diseases, like cancer, need to be properly treated. A few reports have shown that mortality due to SARS-CoV-2 is higher in elderly patients and those with other active comorbidities, including cancer. Patients with lung cancer are at risk of pulmonary complications from COVID-19, and as such, the risk/benefit ratio of local and systemic anticancer treatment has to be considered. For each patient, several factors, including age, comorbidities, and immunosuppression, as well as the number of hospital visits for treatment, can influence this risk. The number of cases is rising exponentially in Brazil, and it is important to consider the local characteristics when approaching the pandemic. In this regard, the Brazilian Thoracic Oncology Group has developed recommendations to guide decisions in lung cancer treatment during the SARS-CoV-2 pandemic. Due to the scarcity of relevant data, discussions based on disease stage, evaluation of surgical treatment, radiotherapy techniques, systemic therapy, follow-up, and supportive care were carried out, and specific suggestions issued. All recommendations seek to reduce contagion risk by decreasing the number of medical visits and hospitalization, and in the case of immunosuppression, by adapting treatment schemes when possible. This statement should be adjusted according to the reality of each service, and can be revised as new data become available.

Lung cancer and the COVID-19 pandemic: recommendations from the brazilian thoracic oncology group

New cases of the novel coronavirus disease 2019 (COVID-19), also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continue to rise worldwide following the declaration of a pandemic by the World Health Organization (WHO). The current pandemic has completely altered the workflow of health services worldwide. However, even during this critical period, patients with other diseases, like cancer, need to be properly treated. A few reports have shown that mortality due to SARS-CoV-2 is higher in elderly patients and those with other active comorbidities, including cancer. Patients with lung cancer are at risk of pulmonary complications from COVID-19, and as such, the risk/benefit ratio of local and systemic anticancer treatment has to be considered. For each patient, several factors, including age, comorbidities, and immunosuppression, as well as the number of hospital visits for treatment, can influence this risk. The number of cases is rising exponentially in Brazil, and it is important to consider the local characteristics when approaching the pandemic. In this regard, the Brazilian Thoracic Oncology Group has developed recommendations to guide decisions in lung cancer treatment during the SARS-CoV-2 pandemic. Due to the scarcity of relevant data, discussions based on disease stage, evaluation of surgical treatment, radiotherapy techniques, systemic therapy, follow-up, and supportive care were carried out, and specific suggestions issued. All recommendations seek to reduce contagion risk by decreasing the number of medical visits and hospitalization, and in the case of immunosuppression, by adapting treatment schemes when possible. This statement should be adjusted according to the reality of each service, and can be revised as new data become available.

Complete pathologic response as a prognostic factor for squamous cell carcinoma of the oropharynx post-chemoradiotherapy / Resposta patológica completa como fator prognóstico no carcinoma espinocelular de orofaringe após quimiorradioterapia

ABSTRACT INTRODUCTION: Chemoradiotherapy for squamous cell carcinoma of the oropharynx (SCCO) provides good results for locoregional disease control, with high rates of complete clinical and pathologic responses, mainly in the neck. OBJECTIVE: To determine whether complete pathologic response after chemoradiotherapy is related to the prognosis of patients with SCCO. METHODS: Data were prospectively extracted from clinical records of N2 and N3 SCCO patients submitted to a planned neck dissection after chemoradiotherapy. RESULTS: A total of 19 patients were evaluated. Half of patients obtained complete pathologic response in the neck. Distant or locoregional recurrence occurred in approximately 42% of patients, and 26% died. Statistical analysis showed an association between complete pathologic response and lower disease recurrence rate (77.8% vs. 20.8%; p = 0.017) and greater overall survival (88.9% vs. 23.3%;p = 0.049). CONCLUSION: The presence of a complete pathologic response after chemoradiotherapy positively influences the prognosis of patients with SCCO.

RESUMO Introdução: O tratamento baseado em quimirradioterapia do Carcinoma Espinocelular de Orofaringe (CECOF) apresenta bons resultados no controle locorregional da doença com boas taxas de resposta clínica e patológica completas especialmente no pescoço. Objetivo: Determinar se a resposta patológica completa após quimiorradioterapia estárelacionada aos prognósticos dos pacientes com CECOF. Método: Os dados foram obtidos de maneira prospectiva da revisão de prontuários de pacientes com CECOF N2 e N3 submetidos a esvaziamento cervical planejado após quimiorradioterapia. Resultados: Um total de 19 pacientes foram avaliados. Metade dos indivíduos apresentou resposta patológica completa no pescoço. Recidiva à distância ou locorregional ocorreu em aproximadamente 42% dos pacientes e 26% deles morreram. A análise estatística demonstrou uma associação entre resposta patológica completa e menor taxa de recidiva (77,8% vs.20,8%; p = 0,017) e maior sobrevivência global (88,9% vs.23,3%; p = 0,049). Conclusão: A presença de resposta patológica completa após quimiorradioterapia influencia positivamente no prognóstico de pacientes com carcinoma espinocelular de orofaringe.

Identifying activating mutations in the EGFR gene: prognostic and therapeutic implications in non-small cell lung cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide. Promising new therapies have recently emerged from the development of molecular targeted drugs; particularly promising are those blocking the signal transduction machinery of cancer cells. One of the most widely studied cell signaling pathways is that of EGFR, which leads to uncontrolled cell proliferation, increased cell angiogenesis, and greater cell invasiveness. Activating mutations in the EGFR gene (deletions in exon 19 and mutation L858R in exon 21), first described in 2004, have been detected in approximately 10% of all non-squamous non-small cell lung cancer (NSCLC) patients in Western countries and are the most important predictors of a response to EGFR tyrosine-kinase inhibitors (EGFR-TKIs). Studies of the EGFR-TKIs gefitinib, erlotinib, and afatinib, in comparison with platinum-based regimens, as first-line treatments in chemotherapy-naïve patients have shown that the EGFR-TKIs produce gains in progression-free survival and overall response rates, although only in patients whose tumors harbor activating mutations in the EGFR gene. Clinical trials have also shown EGFR-TKIs to be effective as second- and third-line therapies in advanced NSCLC. Here, we review the main aspects of EGFR pathway activation in NSCLC, underscore the importance of correctly identifying activating mutations in the EGFR gene, and discuss the main outcomes of EGFR-TKI treatment in NSCLC.

Complete pathologic response as a prognostic factor for squamous cell carcinoma of the oropharynx post-chemoradiotherapy.

INTRODUCTION: Chemoradiotherapy for squamous cell carcinoma of the oropharynx (SCCO) provides good results for locoregional disease control, with high rates of complete clinical and pathologic responses, mainly in the neck. OBJECTIVE: To determine whether complete pathologic response after chemoradiotherapy is related to the prognosis of patients with SCCO. METHODS: Data were prospectively extracted from clinical records of N2 and N3 SCCO patients submitted to a planned neck dissection after chemoradiotherapy. RESULTS: A total of 19 patients were evaluated. Half of patients obtained complete pathologic response in the neck. Distant or locoregional recurrence occurred in approximately 42% of patients, and 26% died. Statistical analysis showed an association between complete pathologic response and lower disease recurrence rate (77.8% vs. 20.8%; p=0.017) and greater overall survival (88.9% vs. 23.3%; p=0.049). CONCLUSION: The presence of a complete pathologic response after chemoradiotherapy positively influences the prognosis of patients with SCCO.

Identifying activating mutations in the EGFR gene: prognostic and therapeutic implications in non-small cell lung cancer / Identificação de mutações ativadoras no gene EGFR: implicações no prognóstico e no tratamento do carcinoma pulmonar de células não pequenas

AbstractLung cancer is the leading cause of cancer-related deaths worldwide. Promising new therapies have recently emerged from the development of molecular targeted drugs; particularly promising are those blocking the signal transduction machinery of cancer cells. One of the most widely studied cell signaling pathways is that of EGFR, which leads to uncontrolled cell proliferation, increased cell angiogenesis, and greater cell invasiveness. Activating mutations in the EGFR gene (deletions in exon 19 and mutation L858R in exon 21), first described in 2004, have been detected in approximately 10% of all non-squamous non-small cell lung cancer (NSCLC) patients in Western countries and are the most important predictors of a response to EGFR tyrosine-kinase inhibitors (EGFR-TKIs). Studies of the EGFR-TKIs gefitinib, erlotinib, and afatinib, in comparison with platinum-based regimens, as first-line treatments in chemotherapy-naïve patients have shown that the EGFR-TKIs produce gains in progression-free survival and overall response rates, although only in patients whose tumors harbor activating mutations in the EGFR gene. Clinical trials have also shown EGFR-TKIs to be effective as second- and third-line therapies in advanced NSCLC. Here, we review the main aspects of EGFR pathway activation in NSCLC, underscore the importance of correctly identifying activating mutations in the EGFR gene, and discuss the main outcomes of EGFR-TKI treatment in NSCLC.

ResumoO câncer de pulmão é a principal causa de mortes por câncer no mundo. Recentemente, novas estratégias promissoras de tratamento foram criadas a partir do desenvolvimento de terapias de alvo molecular, particularmente aquelas que interferem em vias de transdução de sinais em células neoplásicas. Uma das vias de transdução de sinais mais estudadas é aquela ativada a partir do EGFR, que leva a perda do controle da proliferação celular, aumento da angiogênese celular e aumento da capacidade de invasão celular. Mutações ativadoras no EGFR (deleções no éxon 19 e mutação L858R no éxon 21), primeiramente descritas em 2004, foram detectadas em aproximadamente 10% dos pacientes com carcinoma de pulmão de células não pequenas (CPCNP) não escamoso em países ocidentais e são os fatores preditivos mais importantes de resposta aos tyrosine-kinase inhibitors (inibidores de tirosina quinase) do EGFR (EGFR-TKIs). Estudos de tratamento de primeira linha com esses EGFR-TKIs (gefitinibe, erlotinibe e afatinibe) em pacientes sem tratamento sistêmico prévio, em comparação com regimes baseados em platinas, têm demonstrado que os EGFR-TKIs resultam em ganhos em sobrevida livre de progressão e taxas globais de resposta, embora somente em pacientes cujos tumores alberguem mutações ativadoras no EGFR. Ensaios clínicos também mostraram a efetividade dos EGFR-TKIs como tratamentos de segunda e terceira linha de CPCNP avançado. Neste artigo, revisamos os principais aspectos da ativação da via do EGFR em CPCNP, reforçamos a importância da identificação correta das mutações ativadoras no EGFR e discutimos os principais resultados do tratamento do CPCNP com EGFR-TKIs.

Carcinoma anaplásico da tireoide: um caso raro de sobrevivência em longo prazo após tratamento exclusivo com quimiorradioterapia / Anaplastic thyroid carcinoma: rare case of long-term survival after exclusive chemoradioterapy

Paciente masculino, 30 anos, com nódulo em região cervical anterior associado à dispneia progressiva. Tomografia computadorizada de pescoço com massa em lobo tireoidiano esquerdo com invasão das estruturas musculares adjacentes, desvio da traqueia e extensão ao mediastino superior. A lesão era irressecável por invasão circular da traqueia, sendo então apenas realizado biópsia da lesão que evidenciou carcinoma anaplásico da tireoide. Encaminhado para tratamento paliativo com radioterapia concomitante à quimioterapia. Trinta e dois meses após o diagnóstico, o paciente ainda encontra-se assintomático, sem evidência de doença metastática à distância e com doença locorregional radiologicamente estável. Trata-se do primeiro relato de um caso de carcinoma anaplásico de tireoide submetido exclusivamente à paliação com sobrevida desta magnitude e que ainda está em seguimento oncológico.

Thirty year-old male with an anterior cervical nodule associated with progressive dyspnea. Neck computed tomography showed a mass in the left thyroid lobe with adjacent muscular invasion, tracheal deviation and extension to the upper mediastinum. The lesion was unressectable because of tracheal circular invasion and therefore he was submitted just to a biopsy which evidenced thyroid anaplastic carcinoma. Palliative treatment was then performed with radiotherapy concomitant to chemotherapy. Thirtytwo months after diagnosis the patient is still asymptomatic, with no evidence of distant metastatic disease and with local disease radiologically stable. This is the first case report of a patient with thyroid anaplastic carcinoma submitted exclusively to palliation with a survival of this magnitude and still on oncologic follow up.

Osteonecrosis of the mandible associated with bevacizumab therapy.

Bevacizumab is a humanized antibody that blocks vascular endothelial growth factor and is of great value for the treatment of advanced cancer. Several adverse effects following its administration have been reported. To date, only 8 cases of osteonecrosis of the jaws associated with bevacizumab (without any association with bisphosphonates) have been reported. The aim of this article was to describe an original case of bevacizumab-related osteonecrosis of the jaw. A 61-year-old man diagnosed with advanced renal cell carcinoma was undergoing treatment with intravenous bevacizumab and temsirolimus when he spontaneously developed mandible osteonecrosis, which resolved after 3 months of conservative management. The present case reinforces recent speculation that the anti-angiogenic properties of bevacizumab may represent a potential new source of osteonecrosis of the jaws in patients undergoing cancer treatment. Multidisciplinary teams in cancer care should be aware of the possible association between osteonecrosis of the jaw and bevacizumab therapy.

Expressão da proteína ERCC1 (excision repair cross complementing group 1), do seu RNA mensageiro e de polimorfismos genéticos como fatores prognósticos em pacientes portadores de carcinoma epidermóide de cabeça e pescoço operados e submetidos à quimiorradioterapia adjuvante / ERCC1 (excision repair cross complementing group 1) protein, messenger RNA level and genetic polymorphisms as prognostic markers in patients diagnosed with head and neck squamous cell carcinoma treated with surgery and adjuvant chemoradiation

INTRODUÇÃO: Quimiorradioterapia (QRT) concomitante adjuvante aumenta a sobrevida livre de doença (SLD) em pacientes portadores de carcinoma epidermóide de cabeça e pescoço (CECCP) de alto risco operados com intenção curativa, porém está associada a toxicidade não desprezível e seu impacto na sobrevida global (SG) é incerto. ERCC1 (Excision Repair Cross Complementing Group 1) é uma proteína com função crítica no reparo de DNA por excisão de nucleotídeos (NER) e está envolvido na resistência à quimio- e radioterapia. Neste trabalho tivemos como objetivos determinar a expressão da proteína ERCC1, a expressão do RNA mensageiro (mRNA) de ERCC1 e a ocorrência do polimorfismo de nucleotídeo único T19007C de ERCC1 em pacientes portadores de CECCP de alto risco, operados e tratados com QRT adjuvante, bem como o valor prognóstico destes marcadores. MÉTODOS: Trata-se de um estudo retrospectivo em pacientes portadores de CEC de cavidade oral, orofaringe, hipofaringe ou laringe, operados com intenção curativa e portadores de doença de risco alto ou intermediário. Pacientes elegíveis haviam sido tratados com QRT adjuvante: 60-70 Gy e cisplatina concomitante (100 mg/m2, dias 1, 22 e 43), não apresentavam metástases a distância e nem sinais de recidiva após cirurgia. A expressão da proteína ERCC1 foi avaliada por imunohistoquímica, através de um escore H semiquantitativo, obtido pelo produto da intensidade da coloração nuclear (0-3) pelo escore proporcional atribuído à porcentagem estimada de núcleos corados (0;0,1;0,5;1). O método da transcrição reversa e reação em cadeia da polimerase (PCR) em tempo real quantitativo foi utilizado para determinação da expressão do mRNA de ERCC1 em tecido de tumor primário, normalizada em relação à expressão da fração 18S do RNA ribossomal. Genotipagem de ERCC1 (códon 118) foi realizada por PCR - polimorfismo do tamanho do fragmento de restrição a partir de DNA genômico extraído de linfonodos normais destes pacientes, após digestão com...

BACKGROUND: Adjuvant concurrent chemoradiation (CRT) improves diseasefree survival (DFS) in patients diagnosed with head and neck squamous cell carcinoma (HNSCC) presenting with high-risk features treated with surgery with curative intent, but treatment-related toxicity is not negligible and its impact on overall survival (OS) is uncertain. ERCC1 (Excision Repair Cross Complementing Group 1) is a protein with a critical role in the nucleotide excision repair (NER) pathway, associated with resistance to chemo- and radiation therapy. We aimed here to study ERCC1 protein expression, ERCC1 messenger RNA (mRNA) expression and the single nucleotide polymorphism T19007C of ERCC1 as prognostic markers in HNSCC patients presenting with high-risk features treated with surgery and adjuvant CRT. METHODS: It is a retrospective study in patients with oral cavity, oropharynx, hypopharynx or larynx SCC submitted to radical surgery with curative intent and presenting with pathologic features of high- or intermediate-risk. Eligible patients were treated with adjuvant CRT: 60-70 Gy and concurrent cisplatin (100 mg/m2, days 1, 22 and 43), with no distant metastasis and no relapsed disease after surgery. ERCC1 protein expression was evaluated by immunohistochemistry, using a semi-quantitative H-score, calculated by multiplying the nuclear staining intensity (0-3) by the proportion score attributed to the percentage of positive tumor nuclei (0;0,1;0,5;1). Quantitative real-time reverse transcriptase polymerase chain reaction (PCR) assay was performed to determine ERCC1 mRNA expression in primary tumors tissue specimens. The ERCC1 mRNA expression was normalized using 18S fraction of ribosomal RNA expression as internal reference. ERCC1 (codon 118) genotypes were detected using PCR restriction fragment length polymorphism method carried out in genomic DNA extracted from normal lymph nodes. The PCR products were digested with BsrDI. RESULTS: 69 patients...