Demographic and Clinical Outcomes of Brazilian Patients With Stage III or IV Non-Small-Cell Lung Cancer: Real-World Evidence Study on the Basis of Deterministic Linkage Approach.

PURPOSE: Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer and accounts for 80%-90% of the cases. In Brazil, between 2018 and 2019, lung cancer was ranked as the second most frequent cancer among men and the fourth among women. The primary objectives were to describe the journey and survival rates of patients with advanced NSCLC treated in the Brazilian private health care system (HCS). MATERIALS AND METHODS: A retrospective cohort study was based on the search in administrative databases to analyze the Brazilian private HCS. Patients with advanced NSCLC diagnosed between 2011 and 2016 were included. The data on demographics, cancer-related information, treatment-related information, and resources used were collected. Survival analyses were performed using the semiparametric Kaplan-Meier method to assess mortality by NSCLC stage, with NSCLC diagnosis as the index date. RESULTS: A total of 5,016 patients were included. Most patients were between 60 and 69 years old (33.6%) and had completed elementary school (52.2%). There was a greater proportion of men (58.1% v 41.9%), and the majority of patients had stage IV NSCLC (67%). It took an average of 31 days, from the first consultation, to have diagnosis. In 44% of the cases, a clinical oncologist was the first specialist in the HCS that the patient was referred to. After the diagnosis, the median time to start of treatment was 35 days. Chemotherapy alone was the most common treatment regimen (32%). The median overall survival was 11.5 months and 6 months for stage II and IV NSCLC, respectively. CONCLUSION: This study provides contemporary data on stage III and IV NSCLC in private health care in Brazil, which has shown a high rate of metastatic disease diagnoses, high health care-related costs, and low survival rates.

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.

Pembrolizumab plus axitinib and nivolumab plus ipilimumab as first-line treatments of advanced intermediate- or poor-risk renal-cell carcinoma: a number needed to treat analysis from the Brazilian private perspective.

BACKGROUND: Considering clinical benefits of new combination therapies for metastatic renal-cell carcinoma (mRCC), this study aims to calculate the number needed to treat (NTT) and the cost of preventing an event (COPE) for pembrolizumab plus axitinib (P + A), and nivolumab plus ipilimumab (N + I) as first-line treatments, from the Brazilian private perspective. METHODS: Overall survival (OS) and progression-free survival (PFS) data for intermediate- and poor-risk groups were obtained from KEYNOTE-426 and CHECKMATE-214 trials for P + A and N + I, respectively, versus sunitinib as mRCC first-line treatment. RESULTS: Considering a 12-month time horizon, 6 patients should be treated with P + A to prevent one death with sunitinib use, resulting in a COPE of 3,773,865 BRL. Using N + I, NNT for 12-month OS rate was 13 compared to sunitinib, with a COPE of 6,357,965 BRL. Regarding PFS data, NNT was also 6 when comparing P + A versus sunitinib, with an estimated COPE of 3,773,865 BRL. Estimated NNT was 20 comparing N + I and sunitinib, resulting in a COPE of 10,172,744 BRL. Cost differences between two treatment options, reached more than 6 million BRL for PFS, and 2 million BRL for OS. CONCLUSION: At the 12-month landmark, P + A suggests better economic scenario versus N + I as first-line mRCC treatment option for intermediate- and poor-risk groups, through an indirect comparison using sunitinib as a common comparator.

Número necessário a tratar (NNT) e custo por evento evitado (COPE) de enzalutamida e acetato de abiraterona para o tratamento de câncer de próstata resistente à castração que falharam a terapia de privação de androgênio / Number needed to treat (NNT) and cost of preventing an event (COPE) of enzalutamide vs. abiraterone acetate plus prednisone for the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients who failed androgen deprivation therapy (ADT)

Objetivo: O objetivo deste estudo foi estimar o número necessário a tratar (NNT) e custo por evento evitado (COPE) de enzalutamida (ENZ) em comparação com abiraterona+prednisona (AA+P) em 12 e 24 meses sob perspectiva do sistema de saúde suplementar em pacientes com câncer de próstata resistente à castração metastático (CPRCM) sem quimioterapia prévia. Métodos: O NNT é calculado pelo inverso da diferença do risco absoluto de uma intervenção versus placebo; adicionalmente, o COPE representa o NNT multiplicado pelo custo de tratamento total de um período determinado. O risco absoluto de ENZ e AA+P e seus respectivos controles foram obtidos das curvas de sobrevida livre de progressão radiográfica (SLPr) e sobrevida global (SG) dos estudos PREVAIL e COU-AA-302, respectivamente. A duração de tratamento média no horizonte de 24 meses foi estimada utilizando a área sob a curva das respectivas curvas de SLPr. Os resultados foram a comparação entre ENZ e AA+P versus seus respectivos placebos em 12 e 24 meses para NNT e COPE. O custo total de tratamento consistiu em custos de medicamento, monitoramento, e manejo de eventos adversos (≥1%, eventos de interesses especiais). Resultados: A análise de 12 meses resultou em NNTSG/ENZ= 12,79; NNTSLPr/ENZ= 2,59; NNTSG/AA+P= 116,28; NNTSLPr/AA+P= 4,72 e COPESG/ENZ= BRL 1.626.583; COPESLPr/ENZ= BRL 329.701; COPESG/AA+P= BRL 15.144.886; COPESLPr/AA+P= BRL 614.368. Para a análise de 24 meses, os resultados foram: NNTSG/ENZ= 11,00; NNTSLPr/ENZ= 3,58; NNTSG/AA+P= 16,56; NNTSLPr/AA+P= 5,00 e COPESG/ENZ= BRL 1.965.454; COPESLPr/ENZ= BRL 639.327; COPESG/AA+P= BRL 2.833.580; COPESLPr/AA+P= BRL 855.741. Conclusão: Para ambos horizontes de tempo, os resultados foram favoráveis para ENZ vs. AA+P em pacientes com CPRCM.

Objective: The aim of this study was to estimate the NNT and COPE of enzalutamide (ENZ) in comparison with abiraterone acetate+prednisone (AA+P) over a 12-month and 24-month period from the Supplementary Health System perspective in metastatic castration-resistant prostate cancer patients who are chemotherapy naïve (MCRPC). Methods: The NNT is calculated by the inverse of the absolute risk reduction of an intervention vs. control; additionally, COPE represents the NNT multiplied by total cost of treatment in a pre-defined period. The absolute risk of ENZ and AA+P, and their respective control treatments, were obtained from the Kaplan Meier curves for the co-primary end points of radiographic progression free survival (rPFS) and overall survival (OS) from the clinical studies PREVAIL and COU-AA-302, respectively. Mean treatment duration was estimated utilizing the area under curve (AUC) technique from the respective intervention rPFS curves. The results analyzed ENZ or AA+P versus its respective placebo at 12 and 24 months for NNT and COPE. Total treatment cost consisted of drug cost, monitoring cost and adverse event (>=1% incidence and special interest adverse events) related cost. Results: The 12 month analysis resulted in NNTOS/ENZ= 12.79; NNTrPFS/ENZ= 2.59; NNTOS/AA+P= 116.28; NNTrPFS/AA+P= 4.72 and COPEOS/ENZ= BRL 1,626,583; COPErPFS/ENZ= BRL 329,701; COPEOS/AA+P= BRL 15,144,886; COPErPFS/AA+P= BRL 614,368. For the 24-month analysis, the results were: NNTOS/ENZ= 11.00; NNTrPFS/ENZ= 3.58; NNTOS/AA+P=16.56; NNTrPFS/AA+P= 5.00 and COPEOS/ENZ= BRL 1,965,454; COPErPFS/ENZ= BRL 639,327; COPEOS/ AA+P= BRL 2,833,580; COPErPFS/AA+P= BRL 855,741. Conclusion: Across the 12- and 24-month time horizons, the NNT and COPE was favorable for ENZ vs. AA+P in patients with MCRPC.

Measles and rubella antibody status in children after treatment for acute lymphoblastic leukemia

OBJETIVO: Avaliar a história vacinal e a situação da proteção vacinal contra sarampo e rubéola em crianças portadoras de leucemia linfóide aguda após o término do tratamento. MÉTODOS: O estado imunológico contra o sarampo e a rubéola foi avaliado pela técnica ELISA em 22 crianças com leucemia linfóide aguda após o término do tratamento. RESULTADOS: Dos 22 pacientes, 20 haviam recebido previamente duas doses da vacina do sarampo, e 18 deles, uma dose da vacina da rubéola. Soropositivos para sarampo e rubéola resultaram em 65 e 88,9 por cento, respectivamente, sem correlação com idade do paciente, agressividade do tratamento ou tempo decorrido entre final do tratamento e coleta da amostra. CONCLUSÃO: Detectamos falha na proteção vacinal contra sarampo e rubéola em 35 e 11,1 por cento dos casos, respectivamente. Recomendamos, ao final do tratamento para leucemia linfóide aguda, aplicar reforço da vacina contra sarampo, avaliar o estado imunológico contra rubéola e, se necessário, revacinar o paciente.

OBJECTIVE: To assess the vaccination history and the status of vaccine-induced protection from measles and rubella in children after treatment for acute lymphoblastic leukemia. METHODS: Measles and rubella immunological status was assessed by the ELISA technique for 22 children previously treated for acute lymphoblastic leukemia. RESULTS: From the total of 22 patients, 20 had been given two doses of measles vaccine and 18 had had one dose of rubella vaccine. The percentage of patients seropositive for measles and rubella were 65 and 88.9 percent, respectively, with no correlation with age of patient, aggression of treatment or the time passed between the end of treatment and sample collection. CONCLUSIONS: We detected that vaccination had failed against measles and rubella in 35 and 11.1 percent of cases, respectively. We recommend that a measles booster be given after the completion of treatment for acute lymphoblastic leukemia and that rubella immunity status should be assessed at this point, with revaccination performed when necessary.

Synovial sarcoma of the extremities: prognostic factors for 20 nonmetastatic cases and a new histologic grading system with prognostic significance.

PURPOSE: To evaluate 20 cases of nonmetastatic synovial sarcoma of the extremities regarding prognostic factors, and to propose a histologic grading system with prognostic significance. METHODS: The cases of 20 patients (14 females and 6 males) with nonmetastatic synovial sarcomas of the extremities treated between 1985 and 1998, were retrospectively evaluated regarding prognostic factors. A histologic grading system with prognostic significance is proposed. RESULTS: The mean follow-up period was 48.4 months (range, 16-116 months). There was local recurrence in 3 cases (15%), microscopic surgical margin being the only prognostic factor identified. Seven patients (35%) died of the disease in a mean postoperative period of 31.7 months (range, 16-53 months), all with pulmonary or brain metastasis. The survival rate was 65% in 48.4 months of follow-up. CONCLUSION: The unfavorable prognostic factors identified regarding survival were high histologic grade, tumors proximal to the knee or elbow, and spontaneous tumor necrosis over 25%. Local recurrence did not have influence on survival in this study. The presence of mast cells appears to have a positive influence on survival, although statistical significance was not reached (P = 0.07). The oncologic and functional result was good in 6 cases (30%), regular in 7 (35%), and poor in 7 cases (35%).

Synovial sarcoma of the extremities: prognostic factors for 20 nonmetastatic cases and a new histologic grading system with prognostic significance

PURPOSE: To evaluate 20 cases of nonmetastatic synovial sarcoma of the extremities regarding prognostic factors, and to propose a histologic grading system with prognostic significance. METHODS: The cases of 20 patients (14 females and 6 males) with nonmetastatic synovial sarcomas of the extremities treated between 1985 and 1998, were retrospectively evaluated regarding prognostic factors. A histologic grading system with prognostic significance is proposed. RESULTS: The mean follow-up period was 48.4 months (range, 16-116 months). There was local recurrence in 3 cases (15 percent), microscopic surgical margin being the only prognostic factor identified. Seven patients (35 percent) died of the disease in a mean postoperative period of 31.7 months (range, 16-53 months), all with pulmonary or brain metastasis. The survival rate was 65 percent in 48.4 months of follow-up. CONCLUSION: The unfavorable prognostic factors identified regarding survival were high histologic grade, tumors proximal to the knee or elbow, and spontaneous tumor necrosis over 25 percent. Local recurrence did not have influence on survival in this study. The presence of mast cells appears to have a positive influence on survival, although statistical significance was not reached (P = 0.07). The oncologic and functional result was good in 6 cases (30 percent), regular in 7 (35 percent), and poor in 7 cases (35 percent).

OBJETIVO: Avaliar casos de sarcoma sinovial não-metastático das extremidades no que se refere a fatores prognósticos, e propor um sistema histológico de pontuação com significado prognóstico. MATERIAL E MÉTODO: Vinte casos (14 do sexo feminino e 6 do sexo masculino) de sarcomas sinoviais não-metastáticos das extremidades tratados entre 1985 e 1998 no departamento de Ortopedia foram avaliados retrospectivamente no que se refere a fatores prognósticos e está sendo proposto um sistema de pontuação histológico com significado prognóstico. RESULTADOS: A média dos períodos de acompanhamento foi 48,4 meses (mínimo 16 meses, máximo 116). Houve recorrência localizada em 3 casos (15 por cento), sendo a margem cirúrgica microscópica o único fator prognóstico identificado. Sete pacientes (35 por cento) morreram da doença, todos em período pós-operatório médio de 31,7 meses (mínimo 16 meses, máximo 53), todos com metástase pulmonar ou cerebral. A sobrevida foi de 65 por cento em 48,4 meses de acompanhamento. CONCLUSÃO: Os fatores prognósticos desfavoráveis identificados referentes à sobrevida foram: grau histológico alto, tumores proximais de joelho ou cotovelo e necrose espontânea de tumor acima de 25 por cento. Neste estudo, a recorrência localizada não influiu na sobrevida. Parece que a presença de mastócitos influi positivamente na sobrevida, porém não obtivemos significado estatístico (p=0,07). O resultado oncológico e funcional foi bom em seis casos (30 por cento), regular em sete (35 por cento) e insatisfatório em sete (35 por cento).

Measles and rubella antibody status in children after treatment for acute lymphoblastic leukemia.

OBJECTIVE: To assess the vaccination history and the status of vaccine-induced protection from measles and rubella in children after treatment for acute lymphoblastic leukemia. METHODS: Measles and rubella immunological status was assessed by the ELISA technique for 22 children previously treated for acute lymphoblastic leukemia. RESULTS: From the total of 22 patients, 20 had been given two doses of measles vaccine and 18 had had one dose of rubella vaccine. The percentage of patients seropositive for measles and rubella were 65 and 88.9%, respectively, with no correlation with age of patient, aggression of treatment or the time passed between the end of treatment and sample collection. CONCLUSIONS: We detected that vaccination had failed against measles and rubella in 35 and 11.1% of cases, respectively. We recommend that a measles booster be given after the completion of treatment for acute lymphoblastic leukemia and that rubella immunity status should be assessed at this point, with revaccination performed when necessary.

Comparative analysis between osteosarcoma and Ewing's sarcoma: evaluation of the time from onset of signs and symptoms until diagnosis.

OBJECTIVE: The purposes of this study were to describe the early signs and symptoms of osteosarcoma and Ewing's sarcoma, identify symptoms that could be used to help differentiate the two types of tumors, and determine the time elapsed between the onset of signs and symptoms and the definitive diagnosis in our service, providing information and imputus for earlier diagnosis of these tumors. METHODS: A retrospective analysis of the medical dossiers of 365 patients under 30 years of age diagnosed with osteosarcoma or Ewing's sarcoma was performed, and the aspects of the clinical diagnosis were statistically analyzed and compared. RESULTS: The time between the onset of signs and the symptoms was 5.25 months for osteosarcoma and 8.1 months for Ewing's sarcoma, and the most frequent (89.5%) early symptom of osteosarcoma and Ewing's sarcoma was local pain. Symptoms that might aid diagnosis included early local volume increase and the presence of fever. CONCLUSION: The time until diagnosis of both neoplasias was higher than that reported for North America and Europe. Education of the lay public and medical professionals regarding suspicious early signs and symptoms might shorten the delay of diagnosis.

Comparative analysis between osteosarcoma and Ewing's sarcoma: evaluation of the time from onset of signs and symptoms until diagnosis

FINALIDADE: Este estudo propõ-se a esclarecer as características do osteossarcoma e do sarcoma de Ewing, bem como definir o intervalo de tempo decorrido, no Brasil, entre o início dos sinais e dos sintomas e o diagnóstico definitivo, fornecendo subsídios para um diagnóstico precoce desses tumores. MÉTODO: Alguns aspectos dos diagnósticos clínicos do prontuário de 365 pacientes com menos de 30 anos de idade, portadores de osteossarcoma ou sarcoma de Ewing foram analisados de forma retrospectiva e comparativa, seguindo-se uma análise estatística. RESULTADOS: O tempo entre o início de sinais e sintomas e o diagnóstico foi de 5,25 meses no osteossarcoma e 8,1 meses no sarcoma de Ewing; o sintoma mais freqüente (89,5) nas duas neoplasias foi a dor localizada. CONCLUSÃO: O tempo para o diagnóstico de ambas as neoplasias é maior do que o observado em estatísticas norte-americanas e européias.

Parosteal osteosarcoma with myocardial metastasis 13 years after follow-up.

PURPOSE: To report the case of a woman with a diagnosis of grade II (low grade) parosteal osteosarcoma with the occurrence of myocardial metastasis 13 years after resection, and to present a review of the existing literature on the subject. METHODS: Description of the case and review of the literature. CONCLUSION: The review leads to the conclusion that the occurrence of metastasis from parosteal osteosarcoma can occur in up to 38% of the cases, in spite of its relatively low aggressiveness. However, myocardial metastasis of a parosteal osteosarcoma is an event that was not found in the literature.

Parosteal osteosarcoma with myocardial metastasis 13 years after follow-up

PURPOSE: To report the case of a woman with a diagnosis of grade II (low grade) parosteal osteosarcoma with the occurrence of myocardial metastasis 13 years after resection, and to present a review of the existing literature on the subject. METHODS: Description of the case and review of the literature. CONCLUSION: The review leads to the conclusion that the occurrence of metastasis from parosteal osteosarcoma can occur in up to 38 percent of the cases, in spite of its relatively low aggressiveness. However, myocardial metastasis of a parosteal osteosarcoma is an event that was not found in the literature