Tienhan Sandrine Dabakuyo

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.

Response shift effects on measuring post-operative quality of life among breast cancer patients: a multicenter cohort study

PurposeTo characterize response shift effects in patients with breast cancer (BC).MethodsThe QLQ-C30, BR23, and EurQOL-EQ-5D were assessed at baseline and at the end of the first hospitalization. We used the then-test approach to characterize changes in internal standards by calculating the mean difference between the then-test (retrospective measure) and pre-test baseline QoL assessments. The Ideal Scale Approach was also used to assess changes in standards by comparing health and QoL expectancies between baseline and the end of the first hospitalization. Successive Comparison Approach was used to assess changes in values through the longitudinal assessment of the relative importance of EuroQOL dimensions.ResultsThe results of this study showed that recalibration RS effects occurred early after the first hospitalization for 6/15 dimensions of QLQ-C30 (emotional, cognitive, fatigue, insomnia, appetite loss, diarrhea) and 2/8 of BR-23 (future perspective, systemic therapy side effects). Moreover, health and QoL expectancies changed between the baseline and the end of the first hospitalization, and changes in values were seen for the self-care and usual activities dimensions of the EuroQOL-EQ-5D.ConclusionsThe occurrence of RS early after the first hospitalization suggests that it needs to be taken into account to interpret QoL changes in BC.

A multicenter cohort study to compare quality of life in breast cancer patients according to sentinel lymph node biopsy or axillary lymph node dissection

BACKGROUND This prospective multicenter study assessed and compared the impact of different surgical procedures on quality of life (QoL) in breast cancer patients. PATIENTS AND METHODS The EORTC QLQ-C30 and the EORTC QLQ-BR-23 questionnaires were used to assess global health status (GHS), arm (BRAS) and breast (BRBS) symptom scales, before surgery, just after surgery and 6 and 12 months later. The Kruskal-Wallis test with the Bonferroni correction was used to compare scores. A mixed model analysis of variance for repeated measurements was then applied to assess the longitudinal effect of surgical modalities on QoL. RESULTS Before surgery, GHS (P = 0.7807) and BRAS (P = 0.7688) QoL scores were similar whatever the surgical procedure: sentinel node biopsy (SLNB), axillary node dissection (ALND) or SLNB + ALND. As compared with other surgical groups, GHS 75.91 [standard deviation (SD) = 17.44, P = 0.041] and BRAS 11.39 (SD = 15.36, P < 0.0001) were better in the SLNB group 12 months after surgery. Whatever the type of surgery, GHS decreased after surgery (P < 0.0001), but increased 6 months later (P = 0.0016). BRAS symptoms increased just after surgery (P = 0.0329) and until 6 months (P < 0.0001) before decreasing (P < 0.0001). CONCLUSIONS SLNB improved GHS and BRAS QoL in breast cancer patients. However, surgeons must be cautious, SLNB with ALND results in a poorer QoL.

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.

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

BackgroundIt 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.MethodsAll 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.ResultsAmong 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.ConclusionsA 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.

Time to deterioration in quality of life score as a modality of longitudinal analysis in patients with breast cancer.

PURPOSE This prospective multicenter study explored different definitions of time to deterioration (TTD) in quality of life (QoL) scores, according to different cutoffs of the minimal clinically important difference (MCID) as a modality for longitudinal QoL assessment in breast cancer patients. METHODS QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and BR-23 before surgery, after surgery, and 6 and 12 months later. The global health score, arm symptoms score (BRAS), and breast symptoms score were analyzed. For a given baseline score, QoL was considered to have deteriorated if this score decreased by ≥5 points at any time point after baseline. Analyses were repeated using an MCID of 10 points and taking the score after surgery as the reference score (to explore the occurrence of response shift). TTD was calculated using the Kaplan-Meier method and Cox regression was used to identify independent factors associated with TTD. RESULTS Two hundred thirty-five patients underwent axillary lymph node dissection (ALND), 222 underwent sentinel lymph node biopsy (SLNB), and 61 underwent SLNB plus ALND. Patients who underwent SLNB had a significantly longer TTD for the BRAS dimension than those who underwent ALND. Cox multivariate analyses showed that treatment using SLNB and age >59 years were independently associated with longer TTD for the BRAS, whereas surgery elsewhere than at the Centre Georges François Leclerc was associated with a shorter TTD. CONCLUSION Exploration of different definitions of TTD in QoL provides meaningful longitudinal QoL results for clinicians.

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

BackgroundA 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.MethodsA 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.ResultsSix 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.ConclusionsComorbid 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.

Influence of geriatric oncology consultation on the management of breast cancer in older women: A French population-based study

The objective of the present population‐based study was to assess the impact of geriatric oncology consultation on the management of elderly patients with breast cancer and to identify the predictive factors of breast cancer treatment in this population.

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.

A multicenter cohort to compare quality of life in breast cancer patients according to sentinel lymph node biopsy (SNLB) or full axillary clearance (AC)

9633 Background: This prospective study assessed and compared the impact of surgical technique modalities of breast cancer patients on quality of life (QoL). Methods: A pragmatic prospective multic...