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1.
Qual Life Res ; 29(4): 867-878, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31776827

RESUMO

PURPOSE: The time to deterioration (TTD) approach has been proposed as a modality of longitudinal analysis of patient-reported outcomes (PROs) in cancer randomized clinical trials (RCTs). The objective of this study was to perform a systematic review of how the TTD approach has been used in phase III RCTs to analyze longitudinal PRO data. METHODS: A systematic literature search was conducted in PubMed/MEDLINE, the Cochrane Library and through manual search to identify studies published between January 2014 and June 2018. All phase III cancer RCTs including a PRO endpoint using the TTD approach were considered. We collected general information about the study, PRO assessment and the TTD approach, such as the event definition, the choice of reference score and whether the deterioration was definitive or not. RESULTS: A total of 1549 articles were screened, and 39 studies were finally identified as relevant according to predefined criteria. Among these 39 studies, 36 (92.3%) were in advanced and/or metastatic cancer. Several different deterioration definitions were used in RCTs, 10 studies (25.6%) defined the deterioration as "definitive", corresponding to a deterioration maintained over time until the last PRO assessment available for each patient. The baseline score was explicitly stated as the reference score to qualify the deterioration for most studies (n = 31, 79.5%). CONCLUSION: This review highlights the lack of standardization of the TTD approach for the analysis of PRO data in RCTs. Special attention should be paid to the definition of "deterioration", and this should be based on the specific cancer setting.


Assuntos
Deterioração Clínica , Neoplasias/patologia , Neoplasias/terapia , Medidas de Resultados Relatados pelo Paciente , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Comput Methods Programs Biomed ; 214: 106537, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34879326

RESUMO

BACKGROUND AND OBJECTIVE: Longitudinal analysis of patient-reported outcome (PRO) data remains challenging, as no standardization of statistical methods has been proposed, making comparison of PRO results between clinical trials difficult. In this context, the time to deterioration approach has recently been proposed and is regularly used as a modality of longitudinal PRO analysis in oncology. METHODS: Two new SAS macro programs were developed, %TTD and %TUDD, which implement longitudinal analysis of PRO data according to the time to deterioration approach. These programs implement the recommended deterioration definitions. We described the programs with their different functionalities. RESULTS: The %TTD macro calculates the time to first or transient deterioration, and the %TUDD macro calculates the time until definitive deterioration. These macros allow to obtain the survival variables from the time to deterioration approach. We illustrate our programs by presenting different applications on the randomized phase II AFUGEM GERCOR clinical trial. CONCLUSION: The implementation of the deterioration definitions in SAS software allows the dissemination of this approach, in order to move toward the goal of standardization of longitudinal PRO analysis in oncology clinical trials.


Assuntos
Neoplasias , Qualidade de Vida , Humanos , Oncologia , Medidas de Resultados Relatados pelo Paciente , Software
3.
Pharmacogenomics J ; 11(6): 437-43, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20644561

RESUMO

Neoadjuvant radiochemotherapy followed by total mesorectal excision is now the standard treatment for locally advanced rectal cancer. However, tumor response to chemoradiation varies widely among individuals and cannot be determined before the final pathologic evaluation. The aim of this study was to identify germline genetic markers that could predict sensitivity or resistance to preoperative radiochemotherapy (RT-CT) in rectal cancer. We evaluated the predictive value of 128 single-nucleotide polymorphisms (SNPs) in 71 patients preoperatively treated by RT-CT. The selected SNPs were distributed over 76 genes that are involved in various cellular processes such as DNA repair, apoptosis, proliferation or immune response. The SNPs superoxide dismutase 2 (SOD2) rs4880 (P=0.005) and interleukin-13 (IL13) rs1800925 (P=0.0008) were significantly associated with tumor response to chemoradiation. These results reinforce the idea of using germline polymorphisms for personalized treatment.


Assuntos
Biomarcadores Tumorais/genética , Interleucina-13/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Superóxido Dismutase/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Genótipo , Humanos , Desequilíbrio de Ligação , Pessoa de Meia-Idade , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia
4.
Ann Oncol ; 21(1): 98-103, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19889608

RESUMO

BACKGROUND: Pancreatic carcinoma remains a treatment-refractory cancer with a poor prognosis. Here, we compared anti-epidermal growth factor receptor (EGFR) and anti-HER2 monoclonal antibodies (2mAbs) injections with standard gemcitabine treatment on human pancreatic carcinoma xenografts. MATERIALS AND METHODS: Nude mice, bearing human pancreatic carcinoma xenografts, were treated with either combined anti-EGFR (cetuximab) and anti-HER2 (trastuzumab) or gemcitabine, and tumor growth was observed. RESULTS AND CONCLUSION: In first-line therapy, mice survival was significantly longer in the 2mAbs group compared with gemcitabine (P < 0.0001 for BxPC-3, P = 0.0679 for MiaPaCa-2 and P = 0.0019 for Capan-1) and with controls (P < 0.0001). In second-line therapy, tumor regressions were observed after replacing gemcitabine by 2mAbs treatment, resulting in significantly longer animal survival compared with mice receiving continuous gemcitabine injections (P = 0.008 for BxPC-3, P = 0.05 for MiaPaCa-2 and P < 0.001 for Capan-1). Therapeutic benefit of 2mAbs was observed despite K-Ras mutation. Interestingly, concerning the mechanism of action, coinjection of F(ab')(2) fragments from 2mAbs induced significant tumor growth inhibition, compared with controls (P = 0.001), indicating that the 2mAbs had an Fc fragment-independent direct action on tumor cells. This preclinical study demonstrated a significant improvement of survival and tumor regression in mice treated with anti-EGFR/anti-HER2 2mAbs in first- and second-line treatments, compared with gemcitabine, independently of the K-Ras status.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Western Blotting , Linhagem Celular Tumoral , Cetuximab , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/imunologia , Feminino , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Nus , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/imunologia , Trastuzumab , Ensaios Antitumorais Modelo de Xenoenxerto , Gencitabina
5.
Med Decis Making ; 29(3): 343-50, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19073996

RESUMO

Several multistage or group sequential statistical methods have been developed for defining stopping rules in terms of efficacy in phase II and III clinical trials, but they rely on interim analyses after the inclusion of a fixed number of patients. These methods, however, need to be adapted for the evaluation of serious adverse events (SAEs), which can occur relatively early in the trial. A high frequency of their occurrence may require the trial to close early. The methods developed here define stopping rules after the occurrence of each SAE by comparing the number of patients included to the number of patients satisfying maximum SAE criteria. The nominal type I error, power, and average sample number (ASN) under specific hypotheses are obtained through simulations. Data from a clinical trial are presented as an example.


Assuntos
Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Monitorização Fisiológica , Terapêutica/efeitos adversos , Teorema de Bayes , Humanos , Tamanho da Amostra
6.
Comput Methods Programs Biomed ; 158: 153-159, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29544781

RESUMO

BACKGROUND AND OBJECTIVE: Health-related quality of life (HRQoL) has become one relevant and available alternative endpoint of clinical trials in cancer research to evaluate efficiency of care both for the patient and health system. HRQoL in oncology is mainly assessed using the 30-item European Organisation for Research and Treatment of Cancer Quality of Life-Questionnaire Core 30 (EORTC QLQ-C30). The EORTC QLQ-C30 questionnaire is usually assessed at different times along the clinical trials in order to analyze the kinetics of HRQoL evolution and to fully assess the impact of the treatment on the patient's HRQoL level. In this perspective, the realization of a longitudinal HRQoL analysis is essential and the time to HRQoL score deterioration approach is a method which is more and more used in clinical trials. METHOD: Using the Stata software, we developed a QLQ-C30 specific command, qlqc30_TTD, which implements longitudinal strategies based on the time to event methods by considering the time to HRQoL score deterioration. This user-written command providing automatic execution of the Time To Deterioration (TTD) and Time Until Definitive Deterioration (TUDD) methods. RESULT: The program implements all published definitions and provides the Kaplan-Meier curves for each dimension (by group) and a table with the Hazard Ratio and Log-Rank test. CONCLUSION: The longitudinal analysis of HRQoL data in cancer clinical trials remains complex with only few programs like ours computed. This program will be of great help and will allow a more systematic and quicker analysis of the HRQoL data in clinical trials in oncology.


Assuntos
Neoplasias/fisiopatologia , Qualidade de Vida , Humanos , Estudos Longitudinais , Reprodutibilidade dos Testes , Inquéritos e Questionários , Análise de Sobrevida , Fatores de Tempo
7.
Eur J Cancer ; 84: 239-249, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28829992

RESUMO

BACKGROUND: A recent prospective randomised trial did not reveal significant differences in median progression-free survival between two chemoradiotherapy (CRT) regimens for inoperable non-metastatic oesophageal cancer patients. This secondary analysis aimed to describe the impact of CRT on health-related quality of life (HRQOL), physical functioning, dysphagia, fatigue and pain and to evaluate whether baseline HRQOL domains can predict overall survival. PATIENTS AND METHODS: A total of 267 patients were randomly assigned to receive with 50 Gy of radiotherapy in 25 fractions six cycles of FOLFOX or four cycles of fluorouracil and cisplatin on day 1. HRQOL was prospectively assessed using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire version 3.0 with the oesophageal cancer module (QLQ-OES18). RESULTS: Both groups showed high baseline compliance. Subsequently, compliance reduced to 41% at the 6-month follow-up. Baseline HRQOL scores showed no statistical differences between treatment arms. During treatment, both groups exhibited lower physical and social functioning and increased fatigue and dyspnoea, although dysphagia moderately improved in the fluorouracil-cisplatin arm only (p = 0.047). During follow-up, HRQOL scores revealed no significant differences between chemotherapy regimens. Linear mixed model exhibited a treatment-by-time interaction effect for dysphagia (p = 0.017) with a greater decrease in dysphagia in the fluorouracil-cisplatin group. Time until definitive deterioration analysis showed no significant differences in global HRQOL, functional or main symptom domains. However, time until definitive deterioration was significantly longer for the fluorouracil and cisplatin arm compared with FOLFOX for appetite loss (p = 0.002), QLQ-OES-18 pain (p = 0.008), trouble swallowing saliva (p = 0.011) and trouble talking (p = 0.020). CONCLUSION: Analyses of HRQOL scores revealed no statistically significant differences between patients with inoperable non-metastatic oesophageal cancer treated by FOLFOX versus those treated with a fluorouracil-cisplatin regimen as part of definitive CRT.


Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Adenoescamoso/terapia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/métodos , Cisplatino/uso terapêutico , Neoplasias Esofágicas/terapia , Qualidade de Vida , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/psicologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Adenoescamoso/mortalidade , Carcinoma Adenoescamoso/patologia , Carcinoma Adenoescamoso/psicologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/psicologia , Quimiorradioterapia/efeitos adversos , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/psicologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , França , Humanos , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento
8.
Comput Methods Programs Biomed ; 104(2): 243-8, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21741110

RESUMO

In the case of an unexpected high frequency of serious adverse events (SAE), statistical methods are needed to help in the decision making process as to continuation of accrual to the trial. This paper describes an R package, named SAE that implements a method recently developed by defining stopping rules after each observed SAE. The package function control for excessive toxicity either during the trial at the observation of each SAE (function SAE) or during the planning phase of a clinical trial (function DESIGN). This description and the package documentation are complementary to help the users to apply the method. The main difficulty in the implementation of the method is the choice of a priori parameters. Data from an ongoing clinical trial are presented as an example to improve the understanding and the use of the package.


Assuntos
Modelos Teóricos , Antineoplásicos/uso terapêutico , Pré-Escolar , Terapia Combinada , Humanos , Tumores Neuroectodérmicos/tratamento farmacológico , Tumores Neuroectodérmicos/cirurgia
9.
Stat Med ; 24(9): 1435-48, 2005 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-15565738

RESUMO

In epidemiology, we often study data from a mixed distribution, i.e. with a clump of observations at zero and positive continuous data. Lachenbruch developed statistics for this kind of data for independent samples. These tests are the sum of one test for equality of proportions of zero values and one conditional test for the continuous distribution. This paper concerns the adaptation of these tests to paired samples. Like Lachenbruch, we developed two statistics, which tend to a two-degree-of-freedom chi2 distribution. These two-part statistics are the sum of McNemar's test for testing the equality of proportions of zero values, and the Wilcoxon signed-rank test or the paired Student's test for testing the equality of the distribution of positive values. We studied the behaviour of these tests for various proportions of zeros, and mean values of the continuous distribution. All tests are efficient when the smaller proportion of zero values corresponds to the population with the larger mean. In all other situations, the two-part statistics are superior to the others. These methods are applied to a matched case-control study of lower limb venous insufficiency.


Assuntos
Interpretação Estatística de Dados , Métodos Epidemiológicos , Adulto , Estudos de Casos e Controles , Simulação por Computador , Reações Falso-Positivas , Feminino , Número de Gestações , Humanos , Perna (Membro)/patologia , Masculino , Gravidez , Fumar , Varizes/etiologia
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