Fondation ARCAD

BackgroundStandard adjuvant treatment of stage III colon cancer (CC) is fluoropyrimidine with oxaliplatin. Recently, stage III was subdivided into low-risk (T1-3, N1) and high-risk (T4 and/or N2), with the benefit of adding oxaliplatin varying across these substages. In this study, we aimed to assess the impact of oxaliplatin on survival outcomes in subdividing stage III CC patients based on T and N staging.Patients and methodsA total of 4942 stage III CC patients were pooled from the three randomized pivotal trials of oxaliplatin. Kaplan–Meier curves, Cox models stratified by study, and interaction tests were used to assess the oxaliplatin effect across subgroups based on T and N stages. The primary endpoint was overall survival (OS).ResultsThe prevalence of tumor stages was T1-2 12.4%, T3 74.4%, and T4 13.1%; nodal stages were N1 64.7% and N2 35.3%. A significant OS benefit from oxaliplatin was seen only in T3 (5-year OS = 77.2% versus 73.0%, P < 0.001): T3N1 (hazard ratio 0.72, 95% confidence interval 0.62-0.85, P < 0.001) and T3N2 (hazard ratio 0.81, 95% confidence interval 0.69-0.95, P = 0.010). No benefit was observed for T1-2 (5-year OS = 87.8% versus 88.7%, P = 0.644) or T4 patients (5-year OS = 62.6% versus 60.2%, P = 0.648). Subgroup analysis revealed a significant interaction between T stage and the effect of oxaliplatin treatment on OS, whereas no such interaction was observed for N stage.ConclusionsOur analysis revealed that oxaliplatin-based chemotherapy offers a significant survival benefit in stage III CC patients with T3 tumors. In contrast, no survival benefit was observed for T1-2 or T4 patients. These results suggested that T stage plays a more crucial role than N stage in predicting treatment benefit, highlighting the need for tailored treatment strategies based on tumor characteristics.

Meta-analysis based on individual participant data (IPD) is a powerful methodology for synthesizing evidence by combining information drawn from multiple trials. Hitherto, its principal application has been in questions of clinical management, but an increasingly important use is in clarifying trials methodology, for instance in the selection of endpoints, as discussed in this review. In oncology, the Aide et Recherche en Cancérologie Digestive (ARCAD) Metastatic Colorectal Cancer Database is a leader in the use of IPD-based meta-analysis in methodological research. The ARCAD database contains IPD from more than 38 000 patients enrolled in 46 studies and continues to collect phase III trial data. Here, we review the principal findings of the ARCAD project in respect of endpoint selection and examine their implications for cancer trials. Analysis of the database has confirmed that progression-free survival (PFS) is no longer a valid surrogate endpoint predictive of overall survival in the first-line treatment of colorectal cancer. Nonetheless, PFS remains an endpoint of choice for most first-line trials in metastatic colorectal cancer and other solid tumors. Only substantial PFS effects are likely to translate into clinically meaningful benefits, and accordingly, we advocate an oncology research model designed to identify highly effective treatments in carefully defined patient groups. We also review the use of the ARCAD database in assessing clinical response including novel response metrics and prognostic markers. These studies demonstrate the value of IPD as a tool for methodological studies and provide a reference point for the expansion of this approach within clinical cancer research.

Abstract BackgroundCoronavirus disease 2019 (COVID-19) has impacted all age groups, but older adults may have greater distress given their increased risk for severe illness and mortality. In Nepal, most stories of older adults are untold ̶ both in pre-COVID-19 and the COVID-19 era. In this study, we aimed to assess the perceived fear of COVID-19, and associated factors, among older adults in eastern Nepal.MethodsA cross-sectional study was conducted between July and September 2020 among 847 older adults (≥60 years) residing in three districts of eastern Nepal. Perceived fear of COVID-19 was measured using the seven-item Fear of COVID-19 Scale (FCV-19S). In order to examine the factors associated with the COVID 19 fear, a generalized estimating equation, adjusting the sampling design was used. STATA 15 and JASP 0.13.1 were used for data analyses.ResultsThe mean score of the FCV-19S was 18.1±5.2, and a sizeable proportion of participants, ranging between 12%-34%, agreed to the seven items of the fear scale. Increasing age, Dalit ethnicity remoteness to the health facility, and being concerned or overwhelmed with the COVID-19 were associated with greater fear of COVID-19. Surprisingly, pre-existing health conditions were inversely associated with fear of COVID-19.ConclusionGreater fear of the COVID-19 pandemic among the older population suggests that during unprecedented times such as the current pandemic, the psychological needs of most vulnerable groups should be prioritized. Fear among the most vulnerable groups could be reduced with the flow of adequate genuine information as well as better preparedness and psychosocial interventions.