Gemcitabine plus oxaliplatin in advanced hepatocellular carcinoma: a large multicenter AGEO study.

BACKGROUND & AIMS: The current standard treatment for advanced hepatocellular carcinoma (HCC) is sorafenib. This drug is effective but generally does not induce tumor shrinkage and other treatment options are still needed. METHODS: This retrospective multicenter study included all consecutive patients with advanced HCC treated with gemcitabine and oxaliplatin (GEMOX) between 2001 and 2010. Survival curves were drawn with the Kaplan-Meier method and compared with the log-rank test. Univariate and multivariate analyses were used to evaluate prognostic factors. RESULTS: Two hundred four consecutive patients were treated with GEMOX (median age, 60 years; men, 86%; underlying cirrhosis, 76%). Grade 3-4 toxicity was observed in 44% of the patients (thrombocytopenia 24%, neutropenia 18%, diarrhea 14%, neurotoxicity 12%) leading to treatment discontinuation in 16% of the cases. The overall response and disease control rates were 22% (95% CI, 16-27) and 66% (95% CI, 59-72), respectively. No clinical or biological factors were associated with the treatment response, and 8.5% of the patients were subsequently eligible for curative-intent therapies after downstaging. Median PFS, TTP, and OS were 4.5 (95% CI, 4-6), 8 (95% CI, 6-11), and 11 months (95% CI, 9-14), respectively. In multivariate analysis, gender (p=0.03), underlying cirrhosis (p=0.01), CLIP score (p=0.03), and response to GEMOX (p<0.0001) were independently associated with OS. CONCLUSIONS: This large study confirms that GEMOX is effective with manageable toxicity in patients with advanced HCC. Tumor responses permitted potentially curative treatment that was not initially feasible in a significant proportion of patients.

Protocol of the Definition for the Assessment of Time-to-event Endpoints in CANcer trials (DATECAN) project: formal consensus method for the development of guidelines for standardised time-to-event endpoints' definitions in cancer clinical trials.

INTRODUCTION: In randomised phase III cancer clinical trials, the most objectively defined and only validated time-to-event endpoint is overall survival (OS). The appearance of new types of treatments and the multiplication of lines of treatment have resulted in the use of surrogate endpoints for overall survival such as progression-free survival (PFS), or time-to-treatment failure. Their development is strongly influenced by the necessity of reducing clinical trial duration, cost and number of patients. However, while these endpoints are frequently used, they are often poorly defined and definitions can differ between trials which may limit their use as primary endpoints. Moreover, this variability of definitions can impact on the trial's results by affecting estimation of treatments' effects. The aim of the Definition for the Assessment of Time-to-event Endpoints in CANcer trials (DATECAN) project is to provide recommendations for standardised definitions of time-to-event endpoints in randomised cancer clinical trials. METHODS: We will use a formal consensus methodology based on experts' opinions which will be obtained in a systematic manner. RESULTS: Definitions will be independently developed for several cancer sites, including pancreatic, breast, head and neck and colon cancer, as well as sarcomas and gastrointestinal stromal tumours (GISTs). DISCUSSION: The DATECAN project should lead to the elaboration of recommendations that can then be used as guidelines by researchers participating in clinical trials. This process should lead to a standardisation of the definitions of commonly used time-to-event endpoints, enabling appropriate comparisons of future trials' results.

Attending breast cancer screening alone does not explain the detection of tumours at an early stage.

The goal of a screening programme is to allow tumour detection at an early stage when treatments are more effective and less invasive. We examined whether attending breast cancer (BC) screening alone can explain the discovery of tumours at an early stage. Women aged 50-74 years, with a first BC diagnosed from January 2006 to December 2008, were eligible. Patients' personal and family characteristics before their BC diagnosis were collected through a questionnaire. Their tumour characteristics were provided by the Côte d'Or BC registry and staging was performed according to the criteria of the American Joint Committee on Cancer (AJCC) to provide early-stage (AJCC 0/1) and advanced-stage (AJCC 2/3/4) BC. Multivariate logistic regression analyses were performed to identify the predictive factors for the discovery of BC at an early stage. Data from 533 patients with a BC diagnosed from January 2006 to December 2008 were used. Among them, 353 patients (66.2%) had early-stage BC whereas 175 patients (32.8%) had advanced-stage BC. Patients attending mammography screening were more likely to have had early-stage BC (P=0.0003). Multivariate analyses showed that being aged 63-74 years (P=0.008) and having had a previous regular medical follow-up (P=0.02) were independent predictors for the discovery of an early-stage BC. Mammography screening certainly allowed the discovery of BC at an early stage when performed according to the recommended 2-year interval. The regular use of health services could also contribute towards the early detection of tumours and thus towards a reduction in BC mortality.

Population-based study of breast cancer in older women: prognostic factors of relative survival and predictors of treatment.

BACKGROUND: A large proportion of women with breast cancer (BC) are elderly. However, there is a lack of information regarding BC prognostic factors and care in this population. The aims of this study were to assess the prognostic factors of relative survival (RS) among women with BC aged ≥ 75 years old and to identify the predictive factors of treatments administered to this population. METHODS: A population-based study was performed using data from the Cote d'Or breast and gynaecological cancer registry. Women aged 75 years and older with primary invasive BC and resident in Cote d'Or at the time of diagnosis made between January 1998 and December 2008 were retrospectively selected. Prognostic factors of RS were estimated in a generalized linear model with a Poisson error structure. RS rate for the whole population was given at 5 years. Logistic regression models were used to identify the predictors of the treatments administered. RESULTS: Six hundred and eighty-one women were included. Median age at diagnosis was 80. Comorbidities (p = 0.02), pT stage (p = 0.04), metastases (p =< 0.001), having a family doctor (p = 0.03) and hormone-receptor status (p = 0.006) were independent prognostic factors of RS. The RS rate at 5 years for the whole population was 78.2%, 95%CI = [72.2-83.0]. Age, pT stage, metastases, histoprognostic SBR grade, hormone receptor status and comorbidities were frequently found to be predictors of treatment with surgery alone, hormone therapy alone, breast conserving surgery plus adjuvant therapy and mastectomy plus adjuvant therapy. CONCLUSIONS: Comorbid conditions adversely affect survival in older women with breast cancer. Moreover the results of this study showed that there are numerous predictors of the type of treatment administered, and that the most important were age and comorbidities.

For patients with breast cancer, geographic and social disparities are independent determinants of access to specialized surgeons. A eleven-year population-based multilevel analysis.

BACKGROUND: It has been shown in several studies that survival in cancer patients who were operated on by a high-volume surgeon was better. Why then do all patients not benefit from treatment by these experienced surgeons? The aim of our work was to study the hypothesis that in breast cancer, geographical isolation and the socio-economic level have an impact on the likelihood of being treated by a specialized breast-cancer surgeon. METHODS: All cases of primary invasive breast cancer diagnosed in the Côte d'Or from 1998 to 2008 were included. Individual clinical data and distance to the nearest reference care centre were collected. The Townsend Index of each residence area was calculated. A Log Rank test and a Cox model were used for survival analysis, and a multilevel logistic regression model was used to determine predictive factors of being treated or not by a specialized breast cancer surgeon. RESULTS: Among our 3928 patients, the ten-year survival of the 2931 (74.6 %) patients operated on by a high-volume breast cancer surgeon was significantly better (LogRank p < 0.001), independently of age at diagnosis, the presence of at least one comorbidity, circumstances of diagnosis (screening or not) and TNM status (Cox HR = 0.81 [0.67-0.98]; p = 0.027). In multivariate logistic regression analysis, patients who lived 20 to 35 minutes, and more than 35 minutes away from the nearest reference care centre were less likely to be operated on by a specialized surgeon than were patients living less than 10 minutes away (OR = 0.56 [0.43; 0.73] and 0.38 [0.29; 0.50], respectively). This was also the case for patients living in rural areas compared with those living in urban areas (OR = 0.68 [0.53; 0.87]), and for patients living in the two most deprived areas (OR = 0.69 [0.48; 0.97] and 0.61 [0.44; 0.85] respectively) compared with those who lived in the most affluent area. CONCLUSIONS: A disadvantageous socio-economic environment, a rural lifestyle and living far from large specialized treatment centres were significant independent predictors of not gaining access to surgeons specialized in breast cancer. Not being treated by a specialist surgeon implies a less favourable outcome in terms of survival.

Impact of response shift on longitudinal quality-of-life assessment in cancer clinical trials.

The assessment of longitudinal change in subjective patient-reported outcomes such as health-related quality of life (HRQoL) is a key component of many clinical and research evaluations. A major goal of measuring patient-reported HRQoL is to determine to what extent changes in HRQoL reports over time represent true changes in HRQoL due to treatment or cancer and to what extent they reflect measurement error. Indeed, the subjective assessment of HRQoL change is subject to response-shift effects, whereby health changes lead to shifts in internal standards (i.e., 'recalibration'), values (i.e., 'reprioritization') and conceptualization (i.e., 'reconceptualization') of key HRQoL domains. Response shift is a naturally occurring process that could distort the interpretation of change in HRQoL scores over time in interventional studies. Assessing response shift may therefore be needed to obtain a valid and sensitive assessment of change over time. Several methods to detect and measure the size and the direction of response shift are available. In this article, we summarize the methods used to assess and adjust for the response-shift effect in clinical trials. Nevertheless, our understanding of the parameters and processes associated with response shift is very limited. Further research is still needed to better understand how to measure the different components of response shift and how to take them into account in cancer research.