Health Services Access Inequalities in Brazil Result in Poorer Outcomes for Stage III NSCLC-RELANCE/LACOG 0118.

Introduction: Stage III NSCLC is a heterogeneous disease, representing approximately one-third of newly diagnosed lung cancers. Brazil lacks detailed information regarding stage distribution, treatment patterns, survival, and prognostic variables in locally advanced NSCLC. Methods: RELANCE/LACOG 0118 is an observational, retrospective cohort study assessing sociodemographic and clinical data of patients diagnosed with having stage III NSCLC from January 2015 to June 2019, regardless of treatment received. The study was conducted across 13 cancer centers in Brazil. Disease status and survival data were collected up to June 2021. Descriptive statistics, survival analyses, and a multivariable Cox regression model were performed. p values less than 0.05 were considered significant. Results: We recruited 403 patients with stage III NSCLC. Most were male (64.0%), White (31.5%), and smokers or former smokers (86.1%). Most patients had public health insurance (67.5%), had stage IIIA disease (63.2%), and were treated with concurrent chemoradiation (53.1%). The median follow-up time was 33.83 months (95% confidence interval [CI]: 30.43-37.50). Median overall survival (OS) was 27.97 months (95% CI: 21.57-31.73), and median progression-free survival was 11.23 months (95% CI: 10.70-12.77). The type of treatment was independently associated with OS and progression-free survival, whereas the types of health insurance and histology were independent predictors of OS only. Conclusions: Brazilian patients with stage III NSCLC with public health insurance are diagnosed later and have poorer OS. Nevertheless, patients with access to adequate treatment have outcomes similar to those reported in the pivotal trials. Health policy should be improved to make lung cancer diagnosis faster and guarantee prompt access to adequate treatment in Brazil.

EGFR Mutation Detection in Brazilian Patients With Non-Small-Cell Lung Cancer: Lessons From Real-World Data Scenario of Molecular Testing.

PURPOSE: There is a paucity of consistent data concerning genetic mutations in Brazilian patients with lung cancer. The aim of this study was to retrospectively analyze epidermal growth factor receptor (EGFR) mutations detected in a real-world scenario using a large cohort of Brazilian patients with non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: This was a cross-sectional, observational, descriptive study on the basis of a database of EGFR molecular analysis from tumor samples of patients with a confirmatory histopathological diagnosis of primary lung cancer. Specimens were collected from 2013 to 2017 and were tested using cobas, next-generation sequencing, and Sanger sequencing platforms. RESULTS: A total of 7,413 tumor specimens were tested. The patients were predominantly women with a median age of 67.0 years. Patients with at least one mutation represented 24.2% of the total sample. Among the positive patients, the majority had just one mutation, but two or more simultaneous mutations were observed in 1.52% of patients. Exon 19 deletion was the most prevalent alteration in the sample (12.8%), followed by exon 21 L858R (6.9%) and exon 20 insertion (1.6%). All others were considered uncommon mutations and were observed in 18.5% of all mutated patients and 4.0% of the total sample (2.3%-18.7% depending on the sequencing method). CONCLUSION: This study examined the prevalence of EGFR mutations in Brazilian patients with NSCLC using different technologies, suggesting that the type of method used, directed or nondirected against specific mutations, influences the analysis, particularly for uncommon mutations, which will be missed by mutation-specific approaches such as cobas testing. Our estimates are the largest in Latin America and are consistent with previous reports from other parts of the world. Besides the variability in methods described here as technology incorporation advances in a nonhomogeneous manner, it is probably like the real-world clinical setting Brazilian oncologists face in their daily practice.

Real-World Evidence of Health Outcomes Related to Lung Stereotactic Body Radiation Therapy in Brazil.

PURPOSE: Stereotactic body radiation therapy (SBRT) is an effective option for patients with both early-stage and oligometastatic non-small-cell lung cancer (NSCLC). However, data from Latin America are limited. Therefore, the aim of this study was to investigate the real-world outcomes of applying SBRT for lung lesions in a Brazilian institution. METHODS: This study investigated a consecutive cohort of patients treated with SBRT for lung lesions (primary and metastasis). The study primary outcome was local control rates per lesion. Secondary outcomes included progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: Between 2015 and 2019, a total of 216 patients received SBRT and were included in the study. The median follow-up was 24.5 months (5-70), primary NSCLC corresponded to 70% (n = 151) and nonprimary lung lesions to 30% (n = 65), respectively. Stage I NSCLC represented 56% (85 of 151) of the NSCLC cohort. The average number of fractions and total dose prescribed was 5 (3-10)/59 Gy (50-62 Gy). For stage I NSCLC (all lesions treated with a biologically effective dose [10] > 100 Gy), 2-year local control, OS, and PFS were 93.4%, 81.6%, and 80.7%, respectively. For stage IV lesions, if biologically effective dose (10) > 100 Gy or < 100 Gy, 2-year local control was 95.8/86.4% (P = .03), 2-year-OS was 81.6/60.5% (P = .006), and 2-year PFS was 38.9/17.9% (P = .10). Late toxicity was observed in 16.2% (n = 35) of the total cases. CONCLUSION: Our results indicate that SBRT is effective (high local control and acceptable toxicity) for treating malignant lung lesions in a real-world scenario in Latin America.

Assessing Oncologists' Attitudes Concerning Comprehensive Genomic Profiling in Stage IV Lung Adenocarcinoma in Brazil.

Introduction: Advances in comprehensive genomic profiling (CGP) of lung adenocarcinomas (LUADs) led to personalized treatment for patients. This study evaluated medical oncologists' attitudes toward CGP in a scenario where sponsored funding for CGP was available. Methods: We designed an online survey assessing CGP use and treating physicians' confidence, composed of three self-confidence domains, which are as follows: confidence in interpreting CGP results, confidence in treating oncogenic-driven LUAD, and confidence in managing tyrosine kinase inhibitor adverse events. The survey was distributed to medical oncologists who treat lung cancer in Brazil. Comparisons between groups were performed using the chi-square or Fisher's exact test. Univariable and multivariable (adjusted OR) analyses were performed. Results: Among 104 respondents who treat patients with lung cancer, 55% were from the Southeast region, 28% had high lung cancer clinical load, and 33% had in-house molecular testing. More than half (51%) of the participants request CGP systematically to stage IV LUAD. As for provider confidence, 67% stated being confident in all three domains: 76% confident in interpreting CGP, 84% confident in treating oncogenic-driven LUAD, and 81% in managing tyrosine kinase inhibitor adverse events. Providers' confidence was associated with systematically requesting CGP to stage IV LUAD (p = 0.013). After controlling for the variables of interest, systematic requesting CGP for stage IV LUAD revealed a significant association with the provider's confidence (adjusted OR = 0.35, p = 0.028, 95% CI: 0.14-0.84). The major challenge for properly requesting CGP was the long turnaround time and the fear of treatment delays. Conclusions: Even though CGP for stage IV LUAD in Brazil is fully sponsored, only half of the oncologists in our survey systematically request it.. Requesting CGP was associated with providers' confidence. Improving access and promoting providers' awareness of CGP utility is necessary to increase CGP use and better inform treatment decisions.

Role of Stereotactic Radiation Therapy in Operable and Inoperable Early-Stage Non-small Cell Lung Cancer.

OPINION STATEMENT: Radiation therapy is becoming an increasingly important part of non-small cell lung cancer (NSCLC) management. Approximately 60% of all cancer patients require radiation therapy (RT) as part of their treatment. For lung cancer, this number is even higher, reaching approximately 77% of all patients, from radical to palliative modalities of RT. This percentage may even be underestimated, as it may not account for the more recent use of RT in oligometastatic lung cancer patients. Thus, we can estimate that each year there will be approximately 21,890 new lung cancer patients in the USA requiring RT. These numbers are expected to continue to rise, as lung cancer radiation techniques continue to improve. There is growing interest in determining the best treatment options for early-stage NSCLC patients. There is well-established data showing the benefit of RT for inoperable patients, and more recent encouraging data even in operable patients.

Non-Small-Cell Lung Cancer With CNS Metastasis: Disparities From a Real-World Analysis (GBOT-LACOG 0417).

PURPOSE: Despite the advances in the approach to non-small-cell lung cancer (NSCLC) with CNS metastasis, access to timely diagnosis and treatment may not be optimal in many instances. Our main objective was to describe a cohort of patients with NSCLC with brain metastases from public and private cancer centers, and the differences between patients' presentation, treatment, and outcomes. METHODS: GBOT-LACOG 0417 is a multi-institutional retrospective cohort study of patients diagnosed with NSCLC and CNS metastasis in Brazil. All patients had confirmed diagnosis of NSCLC between January 2010 and December 2015. CNS metastases were identified by imaging. RESULTS: A total of 273 patients were included. Patients treated at public institutions were more often Black or Brown (38.8% v 15.4%), current or former smoker (88.6% v 60.0%), of squamous cell histology (25.0% v 9.1%), EGFR- and ALK-negative (95.9% v 74.9%), and were less frequently assessed by using brain magnetic resonance imaging (38.8% v 83.6%). At public institutions, patients were more often symptomatic (78.1% v 44.6%) and had worse performance status (Eastern Cooperative Oncology Group 2 or higher 61.5% v 10.3%). CNS metastases were larger (median size 25 v 15 mm) and more often surrounded by edema (67.7% v 55.2%) at public institutions. Patients at public institutions were more frequently treated with whole-brain radiation therapy (72.9% v 45.4%) and less frequently with radiosurgery (6.3% v 24.1%). Among patients from private care, median overall survival was 24.2 months (95% CI, 20.0 to 30.6), significantly higher than in public care (median 12.1 months; 95% CI, 6.7 to 13.6; P < .001). CONCLUSION: Our results demonstrate the discrepancy between public and private health care system in the critical setting of patients with CNS metastasis from NSCLC.

Number needed to treat analysis applied to pembrolizumab plus chemotherapy for first-line treatment of non-squamous non-small cell lung cancer.

AIMS: Considering that healthcare systems' financial resources are limited, we aimed to analyze the number needed to treat (NNT) and cost of preventing an event (COPE) related to drug use from Supplementary Health System (SSS) perspective. METHODS: Data from KEYNOTE-189 (NCT02578680) were considered, comparing pembrolizumab + chemotherapy to chemotherapy alone. A cost-per-responder model was developed considering the 24- and 12-month time horizons for overall survival (OS) and progression-free survival (PFS) endpoints, respectively. Restricted mean survival time (RMST) and restricted mean time-on-treatment (ToT) were determined for NNT and COPE calculation. Costs were reported in American dollars (USD) and reflect those related to drug use. The analysis was conducted for the total indicated population, and an exploratory assessment was carried out for subgroups with different programmed death-ligand 1 (PD-L1) expression levels. RESULTS: Considering PFS data, the overall population NNTRMST to prevent a progression event with pembrolizumab + chemotherapy versus chemotherapy was 2.63 (95%CI: 1.90-4.02) with an estimated COPE of 251,038 USD (95%CI: 181,359-383,717) in the 12-months follow-up. Regarding OS endpoint, overall NNTRMST and COPE were 3.18 (95%CI: 2.20-5.31) and 414,163 (95%CI: 286,528-691,573) USD respectively, in the 24 months follow-up. The PFS NNT was lower with higher levels of PD-L1 expression (1.71, 3.22 and 5.53 for PD-L1 ≥ 50%, PD-L1 1%-49%, and PD-L1 < 1% groups, respectively), while there was no such apparent relationship for OS (3.23, 4.37 and 2.80 for PD-L1 ≥ 50%, PD-L1 1%-49%, and PD-L1 < 1% groups, respectively). The 95%CIs overlapped for PFS and OS NNT across the PD-L1 subgroups. CONCLUSION: The magnitude of benefit of the pembrolizumab combination used for first-line non-small cell lung cancer (NSCLC) treatment to improve survival compared to chemotherapy alone was confirmed. The exploratory analysis from the SSS perspective suggests no differences among the PDL-1 subgroups in terms of clinical benefit or economic impact.

Patient-centered outcomes in non-small-cell lung cancer: a real-world perspective.

Aims: To assess non-small-cell lung cancer (NSCLC) patient-centered outcomes in the real world. Methods: This is a prospective study of NSCLC patients treated at a private cancer care institution in Brazil between 2014 and 2019. Results: The report comprises 337 patients. Advanced stage was associated with higher symptom burden - fatigue (p = 0.03), pain (p < 0.001) and arm pain (p = 0.022) - and worse global, social and physical functioning (all p < 0.001). In the first 2 years, most factors evolved to either improvement or stability: cough (p = 0.02), pain (p = 0.002), global functioning (p < 0.001) and emotional functioning (p < 0.001). Staging (p < 0.001), fatigue (p = 0.001) and gender (p = 0.004) were independently associated with overall survival. Conclusions: Our results demonstrate the feasibility of conducting real-world prospective analysis of patient-centered outcomes.

Lay abstract This study looked at patient-centered outcomes in lung cancer in a real-world setting. Standardized quality-of-life questionnaires were used to actively measure patients' perception of their functional well-being and health in a clinical setting. Three hundred thirty-seven patients were enrolled in a private cancer center in Brazil between 2014 and 2019. We demonstrated that patients diagnosed at advanced stages presented with more symptoms and lower capacity to perform daily activities. However, symptoms and functioning tended to improve during treatment. Our results show that it is possible to put patients at the heart of cancer care and use their experience to guide clinical approach.

Comprehensive genomic profiling of Brazilian non-small cell lung cancer patients (GBOT 0118/LACOG0418).

BACKGROUND: The aim of this study was to carry out a descriptive analysis of the somatic genetic profile and co-occurring mutations of non-small cell lung cancer (NSCLC) samples from patients tested with comprehensive genomic profiling (CGP). METHODS: This was a retrospective cross-sectional study of patients diagnosed with NSCLC from 2013 to 2018 in Brazil and whose samples were submitted to CGP (FoundationOne or FoundationACT) using either tumor or circulating tumor DNA (ctDNA) from plasma. RESULTS: We recovered 513 CGP results from patients, 457 (89.1%) of which were from tumors and 56 (10.9%) from plasma. The median age of patients was 64 years old, of which 51.6% were males. TP53 mutations were identified in 53.6% of tumor samples, KRAS mutations in 24.2%, EGFR activating mutations were detected in 22.5%, STK11 mutations in 11.6%, PIK3CA mutations in 8.8%, ALK rearrangements in 5.4%, BRAF mutations in 5.2%, and ERBB2 alterations in 4.9%. The most commonly comutated gene was TP53. TP53 p.R337H was observed in 4.3% of samples and was associated with somatic mutations in EGFR and ERBB2 (P < 0.00001). Tumor mutational burden (TMB) analysis was available for 80.5% of samples tested, and 5.5% of samples had high TMB (≥ 20 mutations/Mb). In conclusion, this retrospective analysis of genomic data from NSCLC patients obtained by CGP showed that common abnormalities such as EGFR mutations and ALK rearrangements had similar frequency to those previously described by other groups using others strategies. Additionally, our data confirm an association between TP53 p.R337H, supposedly germline in nature, and somatic mutations in genes of the HER family. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: This is the first report of the prevalence of driver mutations in Brazilian NSCLC patients using comprehensive genomic profiling (CGP). The frequency of the most common driver mutations in this population was similar to that previously described in Brazil. WHAT THIS STUDY ADDS: TP53 was the most commonly comutated gene across samples. TP53 p.R337H was associated with somatic mutations in EGFR and ERBB2. Most samples had low TMB; only 5.5% of samples had high TMB.

Next-generation sequencing of circulating tumor DNA for metastatic non-small cell lung cancer: a discussion on its implementation in the Brazilian clinical practice.

The objective of this review is to address the barriers limiting access to next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) for metastatic nonsquamous non-small cell lung cancer in Brazil and to propose its implementation in practice. A selected panel of lung cancer experts was provided with relevant prompts to address at a conference; a paper was then compiled on the topic. The authors propose specific and realistic recommendations for implementing access to ctDNA NGS. Further, the authors address all barriers and impediments mentioned within this review. There is a great need to increase ctDNA NGS for cancer care in Brazil. Adapting the current cancer testing framework is essential to expanding the use of this tool.

Real-World Molecular Testing and Treatment Patterns in Brazilian Patients with Newly Diagnosed Locally Advanced or Metastatic NSCLC.

OBJECTIVES: To evaluate the molecular testing and treatment patterns in a retrospective cohort of newly diagnosed treatment-naïve patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). METHODS: This is an observational retrospective cohort study conducted across 10 cancer centers in Brazil. Treatment-naïve patients with locally advanced or metastatic NSCLC were enrolled from January to December 2014. The following data were collected from the medical records of patients from diagnosis until the last record (death, loss to follow-up, or the end of the maximum follow-up period): demographics; medical history; smoking status; disease characteristics; previous treatments; and molecular testing patterns and results. The overall survival (OS) was also estimated. RESULTS: A total of 391 patients from 8 different Brazilian states were included, with a median age of 64.1 years (23.7-98.7), with most patients being males (60.1%). The smoking status of 74.2% of patients was a 'former' or 'current smoker'. Stage IV NSCLC at diagnosis was observed in 82.4% of patients, with 269 of them (68.8%) presenting adenocarcinoma (ADC). Among the stage IV ADC patients, 54.0% were referred for molecular testing. Among the patients with an available epidermal growth factor receptor (EGFR) mutation status, 31 (24.0%) were EGFR-positive. The first-line treatment was a platinum-based chemotherapy for 98 patients (25.1%), while non-platinum-based regimens were used in 54 patients (13.8%). OS data were available for 370 patients, with a median OS of 10.8 months. Never smokers had a significantly higher median OS versus current or former smokers (14.6 versus 9.1 months; log-rank p=0.003). Among the patients for whom molecular testing data were available, those with EGFR-positive results had a longer median OS (34.6 versus 12.8 months; log-rank p=0.003). CONCLUSION: Our findings provide relevant information for prescribers and policy decision-makers by highlighting the unmet needs of patients and the importance of molecular testing in newly diagnosed locally advanced or metastatic lung adenocarcinoma. We also highlight the respective EGFR-tyrosine kinase inhibitor treatment when the result is positive and the areas in which further efforts are required to grant access to effective treatment.

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.

Real-world molecular testing and treatment patterns in brazilian patients with newly diagnosed locally advanced or metastatic NSCLC

OBJECTIVES: To evaluate the molecular testing and treatment patterns in a retrospective cohort of newly diagnosed treatment-naïve patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). METHODS: This is an observational retrospective cohort study conducted across 10 cancer centers in Brazil. Treatment-naïve patients with locally advanced or metastatic NSCLC were enrolled from January to December 2014. The following data were collected from the medical records of patients from diagnosis until the last record (death, loss to follow-up, or the end of the maximum follow-up period): demographics; medical history; smoking status; disease characteristics; previous treatments; and molecular testing patterns and results. The overall survival (OS) was also estimated. Results: A total of 391 patients from 8 different Brazilian states were included, with a median age of 64.1 years (23.7-98.7), with most patients being males (60.1%). The smoking status of 74.2% of patients was a 'former' or 'current smoker'. Stage IV NSCLC at diagnosis was observed in 82.4% of patients, with 269 of them (68.8%) presenting adenocarcinoma (ADC). Among the stage IV ADC patients, 54.0% were referred for molecular testing. Among the patients with an available epidermal growth factor receptor (EGFR) mutation status, 31 (24.0%) were EGFR-positive. The first-line treatment was a platinum-based chemotherapy for 98 patients (25.1%), while non-platinum-based regimens were used in 54 patients (13.8%). OS data were available for 370 patients, with a median OS of 10.8 months. Never smokers had a significantly higher median OS versus current or former smokers (14.6 versus 9.1 months; log-rank p=0.003). Among the patients for whom molecular testing data were available, those with EGFR-positive results had a longer median OS (34.6 versus 12.8 months; log-rank p=0.003). Conclusion: Our findings provide relevant information for prescribers and policy decision-makers by highlighting the unmet needs of patients and the importance of molecular testing in newly diagnosed locally advanced or metastatic lung adenocarcinoma. We also highlight the respective EGFR-tyrosine kinase inhibitor treatment when the result is positive and the areas in which further efforts are required to grant access to effective treatment.

Análise de custo-efetividade do painel de sequenciamento de nova geração do DNA circulante tumoral no diagnóstico dos pacientes com câncer de pulmão de não pequenas células não escamoso metastático / Cost-effectiveness analysis of next generation sequencing panel of circulating tumor DNA in the diagnosis of patient with metastatic non-squamous non- small cell lung cancer

Objetivo: Avaliar o impacto clínico e econômico do uso do perfil genômico utilizando Next Generation Sequencing (NGS) em DNA circulante tumoral (ctDNA) na escolha do tratamento de primeira linha (1L) dos pacientes com câncer de pulmão de células não pequenas, não escamoso, metastático e que não apresentam material tecidual suficiente para avaliação das mutações oncogênicas. Métodos: Foi realizada uma análise de custo-efetividade com base em um modelo de árvore de decisão e um modelo de Markov para simular os resultados dos testes diagnósticos e consequentemente o seu impacto clínico e econômico na primeira linha de tratamento. O comparador da análise foi o teste de mutações específicas no gene EGFR por ctDNA. As terapias medicamentosas incluídas na análise foram as terapias-alvo de EGFR e ALK, que estão incorporadas no rol da Agência Nacional de Saúde Suplementar, e a imunoterapia pembrolizumabe combinada à quimioterapia. Os desfechos clínicos foram retirados dos estudos clínicos das terapias avaliadas no modelo. Resultados: O uso do painel de NGS em ctDNA demonstrou uma economia de -R$ 2.076,35 por paciente em um ano, e os resultados de RCEI foram: -R$ 7.652,56 (R$/SLP) e -R$ 33.742,14 (R$/SG). Conclusão: O painel de NGS em ctDNA demonstrou ser uma alternativa dominante em relação ao teste de EGFR em ctDNA.

Objective: The aim of this study was to evaluate the clinical and economic impact of the next generation sequencing (NGS) panel of circulating tumor DNA (ctDNA) in the clinical decision of first line treatment for patients with metastatic non-squamous non-small cell lung cancer who lack of tissue material for evaluation of oncogenic driver mutations. Methods: A cost-effectiveness analysis was performed based on a decision tree model and a Markov model in order to simulate the results of diagnostic tests and therefore its clinical and economic impact in the first line of treatment. The comparators were the single EGFR mutation detection methodologies in ctDNA. The analysis included the anti-EGFR and anti-ALK target therapies; and the combined therapy of pembrolizumab plus chemotherapy. Clinical outcomes were derived from clinical trials of the therapies included in the model. Results: The use of the NGS ctDNA panel showed a saving of -R$ 2,076.35 and the results of the ICER were -R$ 7,652.56 (R$/SLP) and -R$ 33,742.14 (R$/SG). Conclusion: The NGS panel demonstrated to be a dominant alternative in comparison to ctDNA EGFR testing.

Stage III Non-Small-Cell Lung Cancer Treated With Concurrent Chemoradiation Followed or Not by Consolidation Chemotherapy: A Survival Analysis From a Brazilian Multicentric Cohort.

PURPOSE: Of newly diagnosed patients with non-small-cell lung cancer (NSCLC), stage III accounts for 30%. Most patients are treated with concurrent chemoradiation therapy, but the addition of consolidation chemotherapy (CC) is debatable. We examined the effect of CC in Brazilian patients with stage III NSCLC treated in routine clinical practice. METHODS: We retrospectively collected data for patients from five different Brazilian cancer institutions who had stage III NSCLC and who were treated with chemoradiation therapy followed or not by CC. Eligible patients were age 18 years or older and must have been treated with cisplatin-carboplatin plus etoposide, paclitaxel, or vinorelbine, concurrently with thoracic radiation therapy (RT). Patients treated with surgery or neoadjuvant chemotherapy were excluded. The primary end point was overall survival (OS). Associations between CC and clinical variables and demographics were evaluated by using Pearson's χ2 test. Survival curves were calculated by using the Kaplan-Meier method and were compared using the log-rank test. Univariable and multivariable analysis used a Cox proportional hazards model. RESULTS: We collected data from 165 patients. Median age was 60 years. Most patients were male (69.1%), white (77.9%), current or former smokers (93.3%), and had stage IIIB disease (52.7%). Adenocarcinoma was the most common histology (47.9%). Weight loss of more than 5% was observed in 39.1% and Eastern Cooperative Oncology Group performance status of 2 was observed in 14.6%. The only variable associated with CC was T stage ( P = .022). We observed no statistically significant difference in OS between patients treated or not with CC ( P = .128). A total delivered RT dose ≥ 61 Gy was the only variable independently associated with improved survival ( P = .012). CONCLUSION: Brazilian patients with locally advanced NSCLC who were treated with standard treatment achieved OS similar to that reported in randomized trials. CC did not improve OS in patients with stage III NSCLC after concurrent chemoradiation therapy. An RT dose of less than 61 Gy had a negative effect on OS.

Padrões de tratamento, uso de recursos e custo do câncer de pulmão de não pequenas células avançado em instituições brasileiras privadas / Treatment patterns, resource use and cost-of-illness of advanced non-small lung cancer in Brazilian private institutions

Objetivo: No Brasil, dados clínicos e custos econômicos do câncer de pulmão de não pequenas células (CPNPC) são escassos. Portanto, conduzimos este estudo para coletar dados de mundo real sobre padrões de tratamento e uso de recursos para CPNPC avançado (CPNPCa) em pacientes em instituições privadas brasileiras. Métodos: Coletamos dados de prontuários de seis instituições privadas no Brasil. Os pacientes elegíveis tinham diagnóstico de CPNPC avançado ou recorrente (estágios IIIB e IV) entre janeiro de 2011 e julho de 2014, e haviam recebido pelo menos duas linhas de quimioterapia. Dados foram resumidos usando estatísticas descritivas e os custos foram estimados pela abordagem bottom-up. Resultados: Dos 430 pacientes selecionados, 152 foram elegíveis para coleta de dados. A idade mediana dos pacientes foi de 62 anos e 55,9% eram do sexo masculino. Entre os pacientes, 57,2% e 31,6% receberam três e quatro linhas de tratamento, respectivamente. Dezesseis e vinte regimes foram utilizados como tratamentos de primeira e segunda linha. Bevacizumabe carboplatina + paclitaxel (n = 32; 21,1%) foi o mais frequente na primeira linha, enquanto docetaxel isolado (n = 36; 23,7%) foi o regime mais comum de segunda linha. Hospitalizações e visitas ao pronto-socorro foram registradas em 52% e 25% dos pacientes, respectivamente. O custo total da coorte foi de R$ 47.692.195,1 (US$ 14.803.425,4). Conclusões: Os padrões de tratamento para pacientes com CPNPCa em instituições privadas brasileiras são heterogêneos. O alto uso e custos de recursos observados entre os pacientes da CPNPCa têm um impacto econômico significativo para o sistema de saúde privado brasileiro.

Objective: In Brazil, data on clinical and economic burden of non-small cell lung cancer (NSCLC) are scarce. Therefore, we conducted this study to gather real-world data on treatment patterns and resource use for advanced NSCLC (aNSCLC) patients in Brazilian private institutions. Methods: We collected data from medical charts from six private institutions in Brazil. Eligible patients were diagnosed with advanced or recurrent NSCLC (stages IIIB and IV) between January 2011 and July 2014, and had received at least two lines of chemotherapy. Data were summarized using descriptive statistics and costs estimated by bottom-up approach. Results: Out of 430 charts screened, 152 were eligible for data collection. Patients' median age was 62 years, 55.9% were male. Among patients, 57.2% and 31.6% had received three and four treatment lines, respectively. Sixteen and twenty regimens were used as first and second-line treatments, respectively. Bevacizumab + carboplatin + paclitaxel (n = 32; 21.1%) was the most frequent first-line regimens, while docetaxel (n = 36; 23.7%) the most common second-line regimen. Hospitalizations and ER visits were recorded from 52% and 25% of the patients, respectively. Total cohort costs were R$ 47,692,195.1 (US$ 14,803,425.4). Conclusions: Treatment patterns for patients with aNSCLC in Brazilian private institutions are heterogeneous. The observed high resource use and costs among aNSCLC patients have a significant economic impact to the Brazilian private healthcare system.

Lung cancer in Brazil.

Lung cancer is one of the most incident types of cancer and a leading cause of cancer mortality in Brazil. We reviewed the current status of lung cancer by searching relevant data on prevention, diagnosis, and treatment in the country. This review highlights several issues that need to be addressed, including smoking control, patient lack of awareness, late diagnosis, and disparities in the access to cancer health care facilities in Brazil. We propose strategies to help overcome these limitations and challenge health care providers, as well as the society and governmental representatives, to work together and to take a step forward in fighting lung cancer.

Lung cancer in Brazil / Câncer de pulmão no Brasil

ABSTRACT Lung cancer is one of the most incident types of cancer and a leading cause of cancer mortality in Brazil. We reviewed the current status of lung cancer by searching relevant data on prevention, diagnosis, and treatment in the country. This review highlights several issues that need to be addressed, including smoking control, patient lack of awareness, late diagnosis, and disparities in the access to cancer health care facilities in Brazil. We propose strategies to help overcome these limitations and challenge health care providers, as well as the society and governmental representatives, to work together and to take a step forward in fighting lung cancer.

RESUMO O câncer de pulmão é um dos tipos de câncer com maior incidência e uma das principais causas de mortalidade por câncer no Brasil. Revisamos a situação atual do câncer de pulmão por meio de pesquisa de dados relevantes a respeito de prevenção, diagnóstico e tratamento no país. Esta revisão mostra várias questões que precisam de atenção, tais como controle do tabagismo, educação dos pacientes, desconhecimento por parte dos pacientes, diagnóstico tardio e desigualdade de acesso ao tratamento de câncer no Brasil. Propomos estratégias para ajudar a superar essas limitações e desafiamos os profissionais de saúde, a sociedade e os representantes do governo a trabalhar em conjunto e dar um passo à frente na luta contra o câncer de pulmão.

Hypoxia-Mediated Mechanisms Associated with Antiangiogenic Treatment Resistance in Glioblastomas.

Glioblastomas (GBMs) are malignant tumors characterized by their vascularity and invasive capabilities. Antiangiogenic therapy (AAT) is a treatment option that targets GBM-associated vasculature to mitigate the growth of GBMs. However, AAT demonstrates transient effects because many patients eventually develop resistance to this treatment. Several recent studies attempt to explain the molecular and biochemical basis of resistance to AAT in GBM patients. Experimental investigations suggest that the induction of extensive intratumoral hypoxia plays a key role in GBM escape from AAT. In this review, we examine AAT resistance in GBMs, with an emphasis on six potential hypoxia-mediated mechanisms: enhanced invasion and migration, including increased expression of matrix metalloproteinases and activation of the c-MET tyrosine kinase pathway; shifts in cellular metabolism, including up-regulation of hypoxia inducible factor-1α's downstream processes and the Warburg effect; induction of autophagy; augmentation of GBM stem cell self-renewal; possible implications of GBM-endothelial cell transdifferentiation; and vasoformative responses, including vasculogenesis, alternative angiogenic pathways, and vascular mimicry. Juxtaposing recent studies on well-established resistance pathways with that of emerging mechanisms highlights the overall complexity of GBM treatment resistance while also providing direction for further investigation.