ABSTRACT Objective Currently programmed cell death protein 1 (PD-1) inhibitors in combination with other therapies are being evaluated to determine their efficacy in cancer treatment. However, the effect of PD-ligand (L) 1 expression on disease outcomes in stage III (EC III) non-small cell lung cancer is not completely understood. Therefore, this study aimed to assess the influence of PD-L1 expression on the outcomes of EC III non-small cell lung cancer. Methods This study was conducted on patients diagnosed with EC III non-small cell lung cancer who underwent treatment at a tertiary care hospital. PD-L1 expression was determined using immunohistochemical staining, all patients expressed PD-L1. Survival was estimated using the Kaplan-Meier method. Relationships between variables were assessed using Cox proportional regression models. Results A total of 49 patients (median age=69 years) with EC III non-small cell lung cancer and PD-L1 expression were evaluated. More than half of the patients were men, and most were regular smokers. The patients were treated with neoadjuvant chemotherapy, surgery, or sequential or combined chemotherapy and radiotherapy. The median progression-free survival of the entire cohort was 14.2 months, and the median overall survival was 20 months. There was no significant association between PD-L1 expression and disease progression, clinical characteristics, or overall survival. Conclusions PD-L1 expression was not correlated with EC III non-small cell lung cancer outcomes. Whether these findings differ from the association with immune checkpoint inhibitors remains to be addressed in future studies. PD1 PD (PD-1 However PDligand ligand L (L nonsmall non small understood Therefore PDL1 PDL L1 PD-L hospital staining PDL1. L1. KaplanMeier Kaplan Meier method models 4 age69 age 69 age=6 years men smokers surgery radiotherapy progressionfree progression free 142 14 2 14. months characteristics studies (PD- age6 6 age= (PD

ABSTRACT Background: Non-metastatic castration resistant prostate cancer (M0 CRPC) has seen important developments in drugs and diagnostic tools in the last two years. New hormonal agents have demonstrated improvement in metastasis free survival in M0 CRPC patients and have been approved by regulatory agencies in Brazil. Additionally, newer and more sensitive imaging tools are able to detect metastasis earlier than before, which will impact the percentage of patients staged as M0 CRPC. Based on the available international guidelines, a group of Brazilian urology and medical oncology experts developed and completed a survey on the diagnosis and treatment of M0 CRPC in Brazil. These results are reviewed and summarized and associated recommendations are provided. Objective: To present survey results on management of M0 CRPC in Brazil. Design, setting, and participants: A panel of six Brazilian prostate cancer experts determined 64 questions concerning the main areas of interest: 1) staging tools, 2) treatments, 3) side effects of systemic treatment/s, and 4) osteoclast-targeted therapy. A larger panel of 28 Brazilian prostate cancer experts answered these questions in order to create country-specific recommendations discussed in this manuscript. Outcome measurements and statistical analysis: The panel voted publicly but anonymously on the predefined questions. These answers are the panelists' opinions, not a literature review or meta-analysis. Therapies not yet approved in Brazil were excluded from answer options. Each question had five to seven relevant answers including two non-answers. Results were tabulated in real time. Conclusions: The results and recommendations presented can be used by Brazilian physicians to support the management of M0 CRPC patients. Individual clinical decision making should be supported by available data, however, for Brazil, guidelines for diagnosis and management of M0 CRPC patients have not been developed. This document will serve as a point of reference when confronting this disease stage.

RESUMO A pneumonite secundária à imunoterapia é uma complicação rara, com incidência estimada em cerca de 3%. No entanto, trata-se de uma intercorrência de difícil diagnóstico e com grande morbidade, que tem se tornado um desafio para oncologistas e emergencistas. Foram revisados os casos de cinco pacientes que fizeram uso de anti-PD1 (program cell death receptor antagonist 1) para tratamento antineoplásico e que evoluíram com quadro de pneumonite induzida pelo tratamento. Todos os pacientes apresentaram sintomas respiratórios em vigência de tratamento, com imunoterapia e presença de alteração radiológica em vidro fosco. Dentre estes pacientes, apenas um apresentou pneumonite grau 5, com atraso na introdução de corticoidoterapia, indo a óbito em decorrência do quadro. Os outros quatro pacientes apresentaram pneumonite grau 2, sintomática, sendo tratados com corticoidoterapia e evoluindo com melhora clínica e radiológica. Dois pacientes mantiveram o tratamento após o episódio de pneumonite, sem novas complicações pulmonares posteriores, até o momento. A pneumonite induzida por imunoterapia, apesar de ser um evento pouco frequente, pode acarretar grande morbidade, além de ser potencialmente fatal, cabendo à equipe médica ter atenção aos sintomas mais comuns, como tosse e dispneia, para diagnóstico precoce e tratamento efetivo, com uso precoce de corticoide.

ABSTRACT Immunotherapy-induced pneumonitis is a rare complication with incidence estimated around 3%. This disease is difficult to diagnose and has great morbidity. For this reason, it became a challenge for oncologists and emergencists. We reviewed the case of five patients who used anti-PD1 (program cell death receptor antagonist 1) for antineoplastic treatment and developed treatment-induced pneumonitis. All patients had respiratory problems because of immunotherapy and presence of ground-glass radiologic change. Among all patients, only one had grade 5 pneumonitis, and delaying to begin corticosteroid therapy and worsening in clinical picture led to patient death. Other four patients with symptomatic grade 2 pneumonitis underwent corticosteroid therapy and had improvement in clinical and radiologic picture. Two patients were treated after an episode of pneumonitis, and no new pulmonary complications were observed until the end of this study. Immunotherapy-induced pneumonitis, although uncommon, can be potentially fatal. Medical team has the responsibility to pay attention for most common symptoms of the disease such as cough and dyspnea and conduct an early diagnosis and effective early treatment with corticosteroids.

OBJETIVO: A prevenção do câncer anal tem sido aplicada pelos centros de apoio a pacientes com Aids em todo o mundo. Apesar dos esforços empregados, o eficaz controle da doença permanece distante. A dificuldade na prevenção do câncer anal pode resultar, em parte, da ineficácia da ação da terapia antirretroviral sobre o papilomavírus humano (HPV), pois a coinfecção com HIV e HPV parece aumentar o risco das células infectadas pelo HPV em tornarem-se cancerosas. MÉTODOS: Foram avaliados 69 HIV-positivos e 30 pacientes HIV-negativos do sexo masculino, que foram submetidos à avaliação citológica anal por real time-PCR para a presença de HPV, vírus Epstein-Barr, citomegalovírus e herpes vírus tipos (HSV) 1 e 2 além da análise histopatológica de fragmento de mucosa do canal anal. RESULTADOS: A prevalência de neoplasia intraepitelial anal foi de 35% e foi restrita a pacientes HIV-positivos. Os pacientes infectados com o HPV de alto risco e com contagem inferior a 50 células TCD4/µL mostraram taxa de neoplasia intraepitelial anal de 85,7%. A diferença foi significativa quando comparado a pacientes com células TCD4 >200 células/µL (p<0,01). A taxa de coinfecção viral foi de 16,9% dos casos de doenças sexualmente transmissíveis e diretamente correlacionada à carga viral HIV-1 superior a 10,001 cópias/mL (p=0,017). A taxa de neoplasia intraepitelial anal em pacientes coinfectados foi de 36,4% (p=0,047). CONCLUSÕES: Neste estudo, realizado na principal instituição para o tratamento de HIV/Aids na região amazônica do Brasil, a coinfecção anal com HPV, citomegalovírus, HSV-1, HSV-2 e vírus Epstein-Barr ocorreu somente em pacientes HIV-positivos e foi influenciada pela carga viral do HIV-1. Neste estudo, a coinfecção viral anal não representou risco adicional ao desenvolvimento da neoplasia intraepitelial anal.

OBJECTIVE: The prevention of anal cancer is a goal of worldwide Aids support centers. Despite the efforts that have been made and progress in the antiretroviral therapy, effective disease control remains elusive. Difficulty in preventing anal cancer may result from the ineffectiveness of highly active antiretroviral therapy on the human papillomavirus (HPV) since the coinfection with HIV and HPV appears to increase the risk of HPV-infected cells, becoming cancerous. METHODS: We evaluated 69 HIV-positive and 30 HIV-negative male patients who underwent cytological evaluation by RT-PCR for the presence of HPV, Epstein-Barr virus, cytomegalovirus and herpes virus types (HSV) 1 and 2, and histopathology analysis of the anal canal. RESULTS: The prevalence of anal intraepithelial neoplasia was 35% and it was restricted to HIV-positive patients. Patients infected with high-risk HPV and with fewer than 50 TCD4 cells/µL showed an anal intraepithelial neoplasia rate of 85.7% compared to those with TCD4 cells >200 cells/µL (p<0.01). The rate of viral coinfection was 16.9% of the sexual transmitted diseases cases and it was correlated with HIV-1 viral load of more than 10.001 copies/mL (p=0.017). The rate of AIN in coinfected patients was 36.4% (p=0.047). CONCLUSIONS: In this study, at the main institution for the treatment of HIV/AIDS in the Amazon region of Brazil, anal coinfection with HPV, cytomegalovirus, HSV-1, HSV-2 and Epstein-Barr virus occurred only in HIV-positive patients and it was directly influenced by the viral load of HIV-1. In this study, anal viral coinfection showed no additional risk for the development of anal intraepithelial neoplasia.