RESUMO
The original version of this article contained an error in the usage of the term "false positive rate". The intention of the authors in those instances was simply to compare the absolute percentage of false positive results in the study vs the NLST, not to make any observations about false positive rate in the strict statistical sense (i.e. Type I error probability).
RESUMO
BACKGROUND: The National Lung Screening Trial (NLST) in 2011 showed that low-dose CT (LDCT) screening in high-risk groups reduces lung cancer deaths. Major professional organizations, as well as the U.S. Preventative Services Task Force, have endorsed LDCT screening in these select populations. However, major questions remain about whether widespread deployment of CT screening can achieve results similar to the NLST, especially in the community setting. METHODS: A prospective cohort study was initiated in November 2010. Participants at least 50 years old and with at least 20 pack-years of smoking history underwent LDCT screening in a community setting. RESULTS: One hundred and fifty four participants underwent LDCT screening with median follow-up of 2.7 years. Compared with the NLST, there was a higher rate of positive screening tests (35.7 vs. 27.3 %), higher false positive rate (100 vs. 96.4 %), and poor adherence (43 vs. 95 %). Invasive diagnostic follow-up was uncommon and uncomplicated. No interval lung cancer was detected. Late follow-up was mostly attributed to participant or primary care provider preference (67.5 %), participants lost to follow-up (17.5 %), and lack of insurance (10 %). CONCLUSIONS: These findings highlight the potential challenges of generalizing the NLST mortality benefits in the broad deployment of CT screening. Our results support current recommendations that LDCT screening be performed in a highly structured and integrated setting.
Assuntos
Serviços de Saúde Comunitária , Prestação Integrada de Cuidados de Saúde , Neoplasias Pulmonares/diagnóstico por imagem , Doses de Radiação , Tomografia Computadorizada por Raios X , Fatores Etários , Idoso , California , Serviços de Saúde Comunitária/organização & administração , Serviços de Saúde Comunitária/normas , Prestação Integrada de Cuidados de Saúde/organização & administração , Prestação Integrada de Cuidados de Saúde/normas , Reações Falso-Positivas , Feminino , Fidelidade a Diretrizes , Humanos , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Fatores de Risco , Fumar/efeitos adversos , Fatores de Tempo , Tomografia Computadorizada por Raios X/normasRESUMO
BACKGROUND: Vandetanib is a tyrosine kinase inhibitor of both the vascular endothelial growth factor (VEGFR) and epidermal growth factor (EGFR) receptors. The primary objectives of this study were to determine the maximum tolerated dose of vandetanib with capecitabine and oxaliplatin, without and with bevacizumab, for the first line treatment of metastatic colorectal cancer (mCRC), and to define the dose limiting toxicities. MATERIALS AND METHODS: Three cohorts of patients were studied, with capecitabine at 1,000 mg/m(2) twice daily p.o. on days 1-14 of a 3 week cycle, with oxaliplatin i.v. at 130 mg/m(2) on day 1. Vandetanib dosing was 100 mg/day in cohort 1 and 300 mg/day in cohorts 2 and 3. Bevacizumab was added in cohort 3 at 7.5 mg/kg i.v. on day 1 every 3 weeks. RESULTS: Thirteen patients were enrolled and received from one to eight cycles per patient. Grade 4 dermatitis developed in one patient in the first cohort, and the cohort was expanded to six patients with no further dose limiting toxicities (DLT). The second cohort of 3 patients was well tolerated. The third cohort resulted in grade 3 diarrhea, requiring several days of hospitalization and i.v. hydration, in 3 of the 4 patients. Given the severity and duration of diarrhea, each of these was considered a DLT, and therefore cohort 3 was considered to be above the maximum tolerated dose. Six of the 13 patients achieved a partial or complete remission (46%). The time to progression ranged from 2 to 14 months. CONCLUSIONS: Vandetanib at doses of 100 mg and 300 mg daily in combination with capecitabine and oxaliplatin was well tolerated. However, the addition of bevacizumab resulted in severe diarrhea in three out of four patients. Bevacizumab was not well tolerated with vandetanib and XELOX in combination.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab , Capecitabina , Neoplasias Colorretais/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Diarreia/induzido quimicamente , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Oxaloacetatos , Piperidinas/administração & dosagem , Piperidinas/efeitos adversos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversosRESUMO
INTRODUCTION: In 2018, durvalumab was approved by the U.S. Food and Drug Administration as consolidation immunotherapy for patients with stage III NSCLC after definitive chemoradiotherapy (CRT). However, whether durvalumab benefits patients with EGFR-mutated NSCLC remains unknown. METHODS: We conducted a multi-institutional retrospective analysis of patients with unresectable stage III EGFR-mutated NSCLC who completed concurrent CRT. Kaplan-Meier analyses evaluated progression-free survival (PFS) between patients who completed CRT with or without durvalumab. RESULTS: Among 37 patients, 13 initiated durvalumab a median of 20 days after CRT completion. Two patients completed 12 months of treatment, with five patients discontinuing durvalumab owing to progression and five owing to immune-related adverse events (irAEs). Of 24 patients who completed CRT without durvalumab, 16 completed CRT alone and eight completed CRT with induction or consolidation EGFR tyrosine kinase inhibitors (TKIs). Median PFS was 10.3 months in patients who received CRT and durvalumab versus 6.9 months with CRT alone (log-rank p = 0.993). CRT and EGFR TKI was associated with a significantly longer median PFS (26.1 mo) compared with CRT and durvalumab or CRT alone (log-rank p = 0.023). Six patients treated with durvalumab initiated EGFR TKIs after recurrence, with one developing grade 4 pneumonitis on osimertinib. CONCLUSIONS: In this study, patients with EGFR-mutated NSCLC did not benefit with consolidation durvalumab and experienced a high frequency of irAEs. Patients who initiate osimertinib after durvalumab may be susceptible to incident irAEs. Consolidation durvalumab should be approached with caution in this setting and concurrent CRT with induction or consolidation EGFR TKIs further investigated as definitive treatment.