Current and potential biomarkers in gastric cancer: a critical review of the literature.

Gastric cancer is the fourth most common type of cancer worldwide and the second most lethal. Gastric cancer biomarkers can be used for diagnosis, prediction of sensitivity to treatment, and prognosis. The following search terms were applied to PubMed as of December 2020: 'gastric cancer classification', 'gastric cancer epidemiology', 'cancer metastasis' and 'gastric cancer biomarker'. Only experimental studies were reported in the 'biomarkers' section. Some biomarkers can serve as therapeutic targets for antitumoral drugs. The genes analyzed include E-cadherin, RPRM, XAF1, MINT25, TFF1, p16 and p53. The miRNAs analyzed include miR-18a, miR185-5p, miR-125b and miR-21. Some molecules were associated with metastasis of gastric cancer, specifically those involved with EMT process and tissue degradation.

Lay abstract Gastric cancer is the fourth most common type of cancer worldwide and the second most lethal. Gastric cancer biomarkers are molecules that have different expressions in tumor cells than in normal body cells, and can be used for diagnosis, prediction of sensitivity to treatment, and prognosis. Biomarkers in gastric cancer can include genes that suppress tumor progression, genes that increase tumor progression by binding to growth molecules, molecules related to the body's immune response to the tumor, and non-coding RNA molecules (RNA molecules that do not produce proteins but regulate the cell's genetic material). Some biomarkers can serve as therapeutic targets for anti-tumoral drugs.

New Target Therapies in Advanced Non-Small Cell Lung Cancer: A Review of the Literature and Future Perspectives.

INTRODUCTION: Lung cancer (LC) is the most common neoplasm worldwide, and 85% of these tumors are classified as non-small cell lung cancer (NSCLC). LC treatment was initially restricted to cytotoxic chemotherapy-platinum compounds associated with 3rd generation cytotoxic agents (paclitaxel, gemcitabine, pemetrexed) and, more recently, with monoclonal antibodies (bevacizumab, ramucirumab). Advancements in treatment are correlated with prolonged overall survival (OS). Current advances are focused on target therapies. Target agents: Anti-epidermal growth factor receptor (EGFR) therapy consists of 1st and 2nd generation tyrosine kinase inhibitors (TKIs such as erlotinib, afatinib). In 60% of cases, resistance to these TKIs occurs due to T790M mutation in EGFR, which is overcome 3rd generation drugs (osimertinib). Anaplastic lymphoma kinase (ALK) is the target for drugs such as crizotinib, alectinib, ceritinib. Programmed death 1 (PD-1) and its ligand serve as targets for immunotherapy agents such as pembrolizumab, nivolumab, atezolizumab. DISCUSSION: Challenges in NSCLC treatment include resistance to 3rd generation TKIs, the high cost of ALK inhibitors, and the need for further research on new drugs.

Cost-effectiveness and budget impact of lung cancer immunotherapy in South America: strategies to improve access.

AIM: Immune checkpoint inhibitors revolutionized the treatment of non-small-cell lung cancer, although their costs are a limitation. METHODS: The number of patients with non-small-cell lung cancer eligible for immunotherapy was estimated using local epidemiology data. We extracted survival data from RCTs to estimate the life-years saved in a 5-year time horizon. All costs were in local prices converted to US dollars. RESULTS: In the first-line, the budget impact of pembrolizumab decreased by 35% through risk-sharing. In the second-line, patient selection by programmed-death receptor ligand 1 expression decreased the budgetary impact by 45%, and improved cost-effectiveness. Immunotherapy was more cost-effective in the first-line. CONCLUSION: Given current pricing, Immune checkpoint inhibitors are cost-prohibitive in the majority of South American health services. Nevertheless, several strategies should improve access to immunotherapy.

Immune checkpoint inhibitors for advanced non-small cell lung cancer: emerging sequencing for new treatment targets.

Lung cancer is the leading cause of cancer-related deaths in the world. Immune checkpoint inhibitors (ICI) stimulate cytotoxic lymphocyte activity against tumour cells. These agents are available for the treatment of non-small cell lung cancer (NSCLC) after failure of platinum-based therapy. One recent study has demonstrated that ICI monotherapy was superior to platinum-based chemotherapy for first-line treatment. Nevertheless, this benefit was only for a minority of the population (30%) whose tumour programmed death receptor ligand-1 (PD-L1) expression was above 50%. Therefore, several strategies are under investigation. One option for patients with PD-L1 expression lower than 50% may be the combination of ICI with platinum-based chemotherapy or with ICIs against different targets. However, all of these combinations are at an early stage of investigation and may be very expensive or toxic, producing several harmful adverse events.

Cost effectiveness of chemohormonal therapy in patients with metastatic hormone-sensitive and non-metastatic high-risk prostate cancer.

OBJECTIVE: To assess the cost-effectiveness of chemohormonal therapy in patients with metastatic hormone-sensitive and non-metastatic high-risk prostate cancer. METHODS: An analytical decision model was developed to determine the cost-effectiveness of chemohormonal therapy versus androgen deprivation therapy alone in patients with metastatic hormone-sensitive prostate cancer and patients with non-metastatic high-risk prostate cancer. The cost-effectiveness in metastatic patients with a high-volume disease was assessed separately. The model used data from randomized clinical trials and drug acquisition costs in Brazil. In addition, the costs of post-progression therapies have been included in this model. The benefits to health are expressed as the quality-adjusted life-years, and the incremental cost-effectiveness ratios were calculated. RESULTS: Chemohormonal therapy may be associated with improved quality-adjusted life-years for all patient. The improvement was more than six times greater for patients with high-volume metastatic disease. In these patients, the incremental cost-effectiveness ratios were up to 74% lower than the incremental cost-effectiveness ratios of patients with non-metastatic disease. CONCLUSION: Chemohormonal therapy has been more cost-effective in patients with high-volume metastatic disease.

Cost effectiveness of chemohormonal therapy in patients with metastatic hormone-sensitive and non-metastatic high-risk prostate cancer / Custo-efetividade da adição de quimioterapia ao tratamento hormonal do câncer de próstata metastático sensível a hormônio ou localizado de alto risco

ABSTRACT Objective To assess the cost-effectiveness of chemohormonal therapy in patients with metastatic hormone-sensitive and non-metastatic high-risk prostate cancer. Methods An analytical decision model was developed to determine the cost-effectiveness of chemohormonal therapy versus androgen deprivation therapy alone in patients with metastatic hormone-sensitive prostate cancer and patients with non-metastatic high-risk prostate cancer. The cost-effectiveness in metastatic patients with a high-volume disease was assessed separately. The model used data from randomized clinical trials and drug acquisition costs in Brazil. In addition, the costs of post-progression therapies have been included in this model. The benefits to health are expressed as the quality-adjusted life-years, and the incremental cost-effectiveness ratios were calculated. Results Chemohormonal therapy may be associated with improved quality-adjusted life-years for all patient. The improvement was more than six times greater for patients with high-volume metastatic disease. In these patients, the incremental cost-effectiveness ratios were up to 74% lower than the incremental cost-effectiveness ratios of patients with non-metastatic disease. Conclusion Chemohormonal therapy has been more cost-effective in patients with high-volume metastatic disease.

RESUMO Objetivo Avaliar a relação custo-efetividade da adição de quimioterapia hormonal em pacientes com câncer de próstata metastático sensível a hormônio ou localizado de alto risco. Métodos Um modelo de decisão analítico foi desenvolvido para determinar o custo-efetividade da adição de quimioterapia versus a monoterapia de privação de andrógeno para pacientes com câncer de próstata metastático hormônio-sensível e pacientes de alto risco com câncer de próstata não metastático. O custo-efetividade em pacientes metastáticos com um alto volume da doença foi verificado isoladamente. Os dados do modelo foram obtidos de ensaios clínicos randomizados utilizando custos de aquisição de medicamentos no Brasil. Os custos de terapias pós-progressão também foram incluídos no modelo. Os efeitos foram expressos em anos de vida ajustados por qualidade, e foram calculadas as razões de custo-efetividade incremental. Resultados A adição de quimioterapia levou a um ganho de anos de vida ajustados por qualidade para todos os doentes. Este incremento foi seis vezes maior para os pacientes com doença metastática de alto volume. Nestes pacientes, as taxas do custo incremental por anos de vida ajustados por qualidade foram até 74% mais baixos do que o aumento das taxas dos pacientes com doença não metastática. Conclusão A adição de quimioterapia foi mais custo-efetiva para pacientes com doença metastática de alto volume.

PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: updated survival data.

AIM: The treatment of non-small-cell lung cancer has changed after the development of the immune checkpoint inhibitors. Although the most studied biomarker is PD-L1 expression, its clinical significance is still debatable. In this article, we show the updated survival analysis of all published data. METHODS: We searched in network and conference data sources for relevant clinical studies of immunotherapy for non-small-cell lung cancer that assessed the PD-L1 expression even as an exploratory analysis. The updated survival hazard ratios (HR) were included in the analysis. RESULTS: 14 studies with 2857 patients were included (2019 treated with immunotherapy). The response rate was as higher among PD-L1-positive patients (RR: 2.19, 95% CI: 1.63-2.94). PD-L1 expression was also related to better progression-free survival (HR: 0.69, 95% CI: 0.57-0.85) and better overall survival (HR: 0.77, 95% CI: 0.67-0.89). CONCLUSION: PD-L1 overexpression predicts activity as well as better survival for patients treated with immune checkpoint inhibitors.

Disparities in cancer epidemiology and care delivery among Brazilian indigenous populations.

OBJECTIVE:: To assess aspects related to cancer in indigenous population. METHODS:: This is a retrospective study developed in a public university hospital. We included patients with 18 or more years of age, diagnosed with solid tumors, and followed between 2005 and 2015. Clinical features were assessed by descriptive statistics, and survival was evaluated by Kaplan-Meier curves and multivariate Cox regression. RESULTS:: Fifty patients were included. The cancer incidence was 15.73 per 100,000. The mean age at diagnosis was 54 years and most patients were female (58%). Cancer of the cervix (28%) and prostate (16%) were the most common. The mean time between the onset of symptoms and the diagnosis was 9 months and from diagnosis to the treatment was 3.4 months. Disease diagnosed at stage IV (17%) had worse overall survival (HR: 11.4; p<0.05). The 5-year survival rate ranged from 88% for prostate cancer to 0% for lung cancer. All 5-year survival rates were lower as compared to other populations. CONCLUSION:: The most prevalent cancer sites were cervix and prostate. Disease stage and primary site were prognostic factors. OBJETIVO:: Avaliar os aspectos relacionados a câncer em populações indígenas. MÉTODOS:: Estudo retrospectivo conduzido em um hospital universitário público. Foram incluídos pacientes com 18 anos ou mais, diagnosticados com tumores sólidos e acompanhados entre 2005 e 2015. Os aspectos clínicos foram avaliados por meio de estatística descritiva, e a sobrevida foi avaliada por meio de curvas de Kaplan-Meier e regressão multivariada de Cox. RESULTADOS:: Foram incluídos 50 pacientes. A incidência de câncer foi 15,73 por 100 mil. A média de idade ao diagnóstico foi 54 anos, e a maioria era do sexo feminino (58%). O câncer de colo uterino (28%) e o de próstata (16%) foram os mais frequentes. O tempo médio entre o início dos sintomas e o diagnóstico foi 9 meses, e entre o diagnóstico e o tratamento, de 3,4 meses. Doença diagnosticada no estágio IV (17%) resultou em pior sobrevida global (HR: 11,4; p<0,05). A sobrevida em 5 anos variou de 88% para o câncer de próstata a 0% para pulmão. Todas as taxas de sobrevida em 5 anos foram menores em comparação a outras populações. CONCLUSÃO:: Os locais mais frequentes de neoplasia foram colo de útero e próstata. O estágio da doença e o sítio primário foram fatores prognósticos.

Disparities in cancer epidemiology and care delivery among Brazilian indigenous populations / Disparidades na epidemiologia e no tratamento de câncer nas populações indígenas brasileiras

ABSTRACT Objective: To assess aspects related to cancer in indigenous population. Methods: This is a retrospective study developed in a public university hospital. We included patients with 18 or more years of age, diagnosed with solid tumors, and followed between 2005 and 2015. Clinical features were assessed by descriptive statistics, and survival was evaluated by Kaplan-Meier curves and multivariate Cox regression. Results: Fifty patients were included. The cancer incidence was 15.73 per 100,000. The mean age at diagnosis was 54 years and most patients were female (58%). Cancer of the cervix (28%) and prostate (16%) were the most common. The mean time between the onset of symptoms and the diagnosis was 9 months and from diagnosis to the treatment was 3.4 months. Disease diagnosed at stage IV (17%) had worse overall survival (HR: 11.4; p<0.05). The 5-year survival rate ranged from 88% for prostate cancer to 0% for lung cancer. All 5-year survival rates were lower as compared to other populations. Conclusion: The most prevalent cancer sites were cervix and prostate. Disease stage and primary site were prognostic factors.

RESUMO Objetivo: Avaliar os aspectos relacionados a câncer em populações indígenas. Métodos: Estudo retrospectivo conduzido em um hospital universitário público. Foram incluídos pacientes com 18 anos ou mais, diagnosticados com tumores sólidos e acompanhados entre 2005 e 2015. Os aspectos clínicos foram avaliados por meio de estatística descritiva, e a sobrevida foi avaliada por meio de curvas de Kaplan-Meier e regressão multivariada de Cox. Resultados: Foram incluídos 50 pacientes. A incidência de câncer foi 15,73 por 100 mil. A média de idade ao diagnóstico foi 54 anos, e a maioria era do sexo feminino (58%). O câncer de colo uterino (28%) e o de próstata (16%) foram os mais frequentes. O tempo médio entre o início dos sintomas e o diagnóstico foi 9 meses, e entre o diagnóstico e o tratamento, de 3,4 meses. Doença diagnosticada no estágio IV (17%) resultou em pior sobrevida global (HR: 11,4; p<0,05). A sobrevida em 5 anos variou de 88% para o câncer de próstata a 0% para pulmão. Todas as taxas de sobrevida em 5 anos foram menores em comparação a outras populações. Conclusão: Os locais mais frequentes de neoplasia foram colo de útero e próstata. O estágio da doença e o sítio primário foram fatores prognósticos.

Definitive chemoradiotherapy for squamous head and neck cancer: cisplatin versus carboplatin? A meta-analysis.

AIM: Concomitant chemoradiotherapy (with cisplatin or carboplatin) is an option of definitive treatment for squamous head and neck cancer. We aimed to perform a meta-analysis comparing those two platinum agents. MATERIALS & METHODS: We carried out a systematic search on English literature between 1990 and 17 April 2015 according to the Cochrane review guidelines. RESULTS: Five of 60 studies fulfilled inclusion criteria with 491 patients. There was no difference in response rate. Cisplatin tends to be more active systemically than carboplatin, without statistically significance; 5-year survival rate: 30 and 27%, respectively (p = 0.33). CONCLUSION: Despite the trend to improved outcomes in using cisplatin, carboplatin is also active and can be a reasonable option to treat patients.

EGFR and EML4-ALK Updated Therapies in Non-Small Cell Lung Cancer.

BACKGROUND: Non-small cell lung cancer is the leading cancer-related cause of death. OBJECTIVE: We review the latest therapies for NSCLC with EGFR and ELM4-ALK mutations as well as the most relevant studies and promising patents. METHOD: A literature search of PubMed database was carried out to identify recent Clinical Trials using EGFR therapies and novel patents involving diagnosis and therapies on NSCLC. We conducted a search to find new therapy strategies, new biomarkers, and selected five patents we find relevant. RESULTS: Over the last few years, identification of cancer harboring epidermal growth factor receptor mutations (EGFR) or chromosomal rearrangements of anaplastic lymphoma kinase (ALK) led to new ways in classifying and treating NSCLC. On the other hand, acquired resistance are a constantly challenge in the management of patients with these mutations and new drugs options are in development to improve and amplify treatment strategies. CONCLUSIONS: Currently, EGFR TKIs (e.g.: erlotinib, gefitinib, osimertinib) and ALK inhibitors (crizotinib, ceritinib, alectinib) provided a new face for advanced NSCLC outcomes. To understand the disease molecular profile is mandatory to define the best approach for each patient.

A pooled analysis of nivolumab for the treatment of advanced non-small-cell lung cancer and the role of PD-L1 as a predictive biomarker.

BACKGROUND: Recent studies with nivolumab (a monoclonal antibody against programmed cell death 1 [PD-1] receptor) have shown promise non-small-cell lung cancer (NSCLC) treatment. METHODS: To review available clinical trials data in order to assess nivolumab efficacy and the role of tumoral PDL-1 expression as a biomarker. RESULTS: Nine eligible studies included 2102 patients. In the second line setting, nivolumab achieved a 1-year survival rate of 41%; and in the first line, a 1-year survival rate of 76%. For those with PD-L1 expression <1%, nivolumab showed a trend for improved survival compared with docetaxel. CONCLUSIONS: The available data reinforce nivolumab activity against NSCLC in first-line or subsequent lines. Although PD-L1 expression is related to greater response, PD-L1 negative patients had also some benefit.

The role of PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: a network meta-analysis.

BACKGROUND: Tumor programmed death ligand one (PD-L1) expression has been studied in several trials in non-small-cell lung cancer. METHODS: We assessed the potential role of PD-L1 expression according to Cochrane Collaboration's Guidelines. RESULTS: 13 studies with 1979 patients were included. Among 915 PD-L1 negative patients this rate was 13% (RR 2.08; 95% CI: 1.49-2.91; p < 0.01). The response rate has increased concurrent to the PD-L1 expression (Pearson's correlation, r = 0.43). PD-L1 expression was also related to better 24-weeks progression-free rate (RR 0.79; 95% CI: 0.71-0.89) and a trend toward better 1-year overall survival rate (RR 0.96; 95% CI: 0.87-1.06). CONCLUSION: Taking this data in account, PD-L1 overexpression could not be currently considered a robust biomarker to tailor the immune checkpoint inhibitors treatment.

Current advances in targeted therapies for metastatic gastric cancer: improving patient care.

In this article, we review the literature on the current advances in targeted therapies for metastatic gastric cancer aimed at improving patient care. We conclude that the key to guiding targeted therapy is individual biomarkers, which are not completely elucidated. HER2 overexpression is the only predictive biomarker currently in use. Furthermore, it is necessary to understand that gastric tumors are heterogeneous; therefore, is impossible to evaluate a novel biological compound without evaluating personal biomarkers. The selection of patients who are able to receive each treatment is paramount for improving advanced gastric cancer survival and reducing unnecessary costs.

Evoluçäo do câncer de pulmäo de acordo com a perda de peso / Lung cancer evolution in accordance with the weight loss

Este trabalho analisa os principais fatores em oncologia: índice de Karnofsky, anorexia, estadiamento, tipo histológico, sobrevida, níveis de hemoglobina, fosfatase alcalina, desidrogenase lática, número de linfócitos, antígeno carcinoembrionário, proteínas totais em relação a perda de peso em pacientes portadores de câncer de pulmão. Foram estudados 124 pacientes acompanhados em ambulatório, sendo 91 homens e 33 mulheres com idade média de 62,4 anos. A maioria dos pacientes apresentaram perda de peso superior a 10 por cneto do peso habitual (54,8 por cento). A diferença foi estatisticamente significante no índice de Karnofsky (p=0.03), anorexia (p=0,012), estadiamento (p=0.0001) e metástases à distância. Quanto à sobrevida, embora não-significante estatisticamente, sua tendência se mostrou proporcional à perda de peso. No restante não houve diferença estatisticamente significante. Concluímos que a perda de peso apresenta correlação com os principais fatores que interferem com a nutrição, tornando-se uma importante ferramenta de acompanhamento dos portadores de câncer de pulmão.