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Background: The use of potential surrogate end points for overall survival, such as disease-free survival (DFS) or time-to-treatment failure (TTF) is increasingly common in randomized controlled trials (RCTs) in cancer. However, the definition of time-to-event (TTE) end points is rarely precise and lacks uniformity across trials. End point definition can impact trial results by affecting estimation of treatment effect and statistical power. The DATECAN initiative (Definition for the Assessment of Time-to-event End points in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for RCT in sarcomas and gastrointestinal stromal tumors (GIST)., Methods: We first carried out a literature review to identify TTE end points (primary or secondary) reported in publications of RCT. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points. Recommendations were developed through a validated consensus method formalizing the degree of agreement among experts., Results: Recommended guidelines for the definition of TTE end points commonly used in RCT for sarcomas and GIST are provided for adjuvant and metastatic settings, including DFS, TTF, time to progression and others., Conclusion: Use of standardized definitions should facilitate comparison of trials' results, and improve the quality of trial design and reporting. These guidelines could be of particular interest to research scientists involved in the design, conduct, reporting or assessment of RCT such as investigators, statisticians, reviewers, editors or regulatory authorities., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aim: 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., Methods: A total of 206 women aged 75 years and older with breast cancer, diagnosed from January 2007 to December 2009 were included. The independent impact of geriatric oncology consultation on treatment was analyzed using multivariate logistic regression with adjustment for the other predictive factors of treatment., Results: Patients who had a geriatric oncology consultation (19.4%) had more comorbidities (Charlson Comorbidity Index ≥ 1; P = 0.02), more advanced tumors (P = 0.025), more aggressive tumors (P = 0.029), were more likely to receive mastectomy and adjuvant therapy (P < 0.0001); and less likely to be treated by breast-conserving surgery and adjuvant therapy (P = 0.003). Regarding the geriatric oncology database, 36 of the 40 patients consulted a geriatrician about oncological treatment, and 27 of these 36 patients received the treatment suggested by the geriatrician. For the whole population, geriatric oncology consultation remained a positive predictor for mastectomy and adjuvant therapy (odds ratio 2.32, P = 0.043), and a negative predictor for breast-conserving surgery and adjuvant therapy (odds ratio 0.38, P = 0.048)., Conclusions: In the present study, we found that treatment of patients who underwent a geriatric oncology consultation generally followed the geriatricians' recommendations. The geriatric oncology consultation was a positive predictor of mastectomy and adjuvant therapy, and a negative predictor of breast-conserving surgery and adjuvant therapy., (© 2014 Japan Geriatrics Society.)

This population-based study aimed to describe the effects of neoadjuvant chemotherapy (NC) on survival in breast cancer (BC) patients in daily practice. BC patients treated with NC followed by surgery and radiotherapy, were retrospectively selected from 1982 to 2005 using the Côte d'Or BC registry. These patients were matched for the baseline AJCC (American Joint Committee on Cancer) stage, age at diagnosis, date of diagnosis and oestrogens receptors status to those who had undergone surgery followed by adjuvant chemotherapy and radiotherapy. The prognostic effect of NC on survival in BC patients was assessed with relative survival (RS) analyses. From 1982 to 2005, 210 patients with BC diagnosed in Côte d'Or were treated with NC followed by surgery and radiotherapy. For these patients, mean age at diagnosis was 50 (SD = 11). The main tumour characteristics were clinical AJCC stage 3 (46%) and an advanced Scarff Bloom and Richardson (SBR) stage (80%). Breast conserving surgery was performed in 84 patients (40%), 151 patients (72%) were treated with anthracyclines as the NC and the 5-year RS rate was 71%. Among these patients, 92 (37%) were matched. In this population, multivariate analyses showed that the use of NC did not independently influence RS: relative excess risk = 0.93 (0.50, 1.71)., (© 2013 John Wiley & Sons Ltd.)

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.

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., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Purpose: To characterize response shift effects in patients with breast cancer (BC)., Methods: The 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., Results: The 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., Conclusions: The occurrence of RS early after the first hospitalization suggests that it needs to be taken into account to interpret QoL changes in BC.

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., (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Breast cancer in men is rare, and clinical trials are thus not feasible. This study aimed to describe the epidemiological characteristics, treatment and prognostic factors of breast cancer in men. A population-based study was performed using data from the Cote d'Or breast and gynaecological cancer registry. Data on male breast cancer diagnosed from 1982 to 2008 were provided. Relative survival rates were estimated at 5 years according to the characteristics of the patient and tumour, and treatment. Prognostic factors of survival in men with breast cancer were identified using a generalised linear model. Seventy-five men with invasive breast cancer were registered. Mean age at diagnosis was 66 years. The use of adjuvant chemotherapy (P= 0.013) and hormone therapy (P < 0.0001) increased over time. Relative survival rate at 5 years was 69% for the whole population. Analysis of relative survival according to the treatment showed that survival was longer for patients treated with surgery + radiotherapy + hormone therapy: 89% at 5 years. Scarff, Bloom and Richardson grade was independent prognostic factor of survival. Male breast cancer is a rare disease with a poor prognosis, and diagnosis is often made at an advanced stage. Early diagnosis and better knowledge of the disease would certainly lead to improvements in the prognosis., (© 2012 Blackwell Publishing Ltd.)

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.

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.

Factors affecting the adequacy of breast cancer screening rounds and the clinical implications of screening have been investigated in women aged 50-74 years. Questionnaires were sent to all eligible patients and to the family doctor of those patients who had died or were lost to follow-up at the time of the study. Unlike the tumour characteristics the patients' personal and family characteristics were also collected before the diagnosis. The clinical features of screening-detected tumours and those discovered on clinical signs or on metastasis were compared. On the basis of the time between two mammographies, we created the following four groups according to the recommended screening round: adequate, long, short and patients with no earlier mammography. Univariate and multivariate generalized logit models were obtained to determine factors affecting the adequacy of breast cancer screening rounds. Five hundred and thirty-three patients were included. Two hundred and seventy-seven (52%) had inadequate breast cancer screening rounds (long, short or no earlier mammography). The American Joint Committee on Cancer stage was less advanced (0/1) in screening-detected tumours and among tumours of patients with an adequate screening round (P=0.014). Multivariate analyses showed that patients with an earlier organized screening mammography (P<0.0001) and those with gynaecological follow-up (P=0.03) were more likely to have an adequate rather than an inadequate breast cancer screening round. Screening leads to the detection of early-stage tumours when it is performed according to the recommendations. Organizing mammography rounds as recommended is essential to optimize the benefits of breast cancer screening.

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.

Background: The aim of this population-based study was to assess independent prognostic factors in ovarian cancer using relative survival (RS) and to investigate changes in RS rates from 1982 to 2005., Methods: Data on 748 patients with ovarian cancer were provided by the Côte d'Or gynaecologic cancer registry. The RS was estimated using a generalized linear model with a Poisson error structure. Relative survival and its 95% confidence interval (CI) were described at the following specific time points 1, 3 and 5 years. The effect of prognostic factors on survival was assessed with multivariate analyses of RS., Results: The median follow-up was 12 years. The RS rates at 1, 3 and 5 years were 81%, 55% and 44%, respectively. As compared with the period 1982-1989, an improvement in survival was found for the period 1998-2005: HR = 0.52[0.40-0.67]. Women who lived in urban areas had better RS: HR = 0.82[0.67-0.99]. Patients with epithelial types of ovarian cancer other than mucinous or endometrioid cancer had worse RS than those with serous histology. Age ≥ 70 years was associated with lower survival., Conclusions: Period of diagnosis, stage at diagnosis, histology, place of residence and age were independent prognostic factors for survival in ovarian cancer. An improvement in the survival rate was observed after 1998 but a significant improvement was limited to advanced stage cancers.

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.

Background: Few population-based studies have reported jointly analyses of relative survival according to the following prognostic factors: tumour-node-metastasis (TNM) stage, age, number of examined and positive nodes, hormonal status, histological Scarff, Bloom and Richardson (SBR) grade, tumour extension, hormone receptor status and tumour multifocal status., Patients and Methods: Data on female invasive breast cancer were provided by the Cote d'Or breast cancer registry. The Kaplan-Meier method and log-rank test were used to estimate and compare the survival probability at 1, 5, 10 and 15 years. The effect of prognostic factors on survival was assessed with crude and relative multivariate survival analyses., Results: Crude survival seemed to be worse in patients aged >60 years compared with those aged 45-60 (P > 0.0001), whereas relative survival did not differ. TNM stage, histological SBR grade, progesterone receptor status, tumour multifocal status, locoregional extension and the period of diagnosis were independent prognostic factors of crude and relative survival., Conclusion: Breast cancer is influenced by many factors. Despite the absence of any association between the number of examined nodes and overall survival in this study, the number of nodes removed, in conjunction with other prognostic factors, may be useful in selecting node-negative patients for systemic therapy.