Impact of body composition on outcome in patients with early breast cancer.

PURPOSE: We investigated the impact of body composition on outcomes of patients with early breast cancer. Skeletal muscle mass, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and muscle fat infiltration or inter-muscular adipose tissue areas (IMAT), obtained by computed tomography (CT), were assessed. METHODS: A total of 119 female patients who had breast cancer were included in this retrospective study. The total skeletal muscle and fat tissue areas were evaluated in two adjacent axial slices obtained at the third lumbar vertebra by CT used for disease staging. The women were assigned to either a sarcopenia or non-sarcopenia group based on their skeletal muscle index (cut-off 41.0 cm2/m2). They also were classified into high and low VAT/SAT ratio groups and assigned to either the high or low IMAT index group. The association of the body composition parameters and prognosis was statistically analyzed. RESULTS: Among the 119 evaluable patients, 58 were sarcopenic (48.8%), 55 (46.2%) had a high VAT/SAT ratio, and 62 (52.1%) had a high IMAT index. Median follow-up was 52.4 months. Multivariate analysis revealed sarcopenia and IMAT index as independent prognostic factors for disease-free survival (p = 0.02 and p = 0.04, respectively) and overall survival (p = 0.05 and p = 0.02, respectively). BMI was not significantly associated with disease-free survival, but a trend was observed (p = 0.09). CONCLUSIONS: Sarcopenia and IMAT index are independent prognostic factors in early breast cancer; therefore, assessing body composition could be a simple and useful approach to integrate into patient management.

Assessment of Ki67 and uPA/PAI-1 expression in intermediate-risk early stage breast cancers.

BACKGROUND: The objective of this study was to compare the efficacy of biomarkers in assessing the risk of breast cancer recurrence in patients with node-negative or micrometastatic grade II breast cancer. Specifically, we compared risk assessments based on the St. Gallen clinicopathological criteria, Ki67 expression and urokinase plasminogen activator (uPA)/plasminogen activator inhibitor-1 (PAI-1) expression. METHODS: This retrospective study included 347 patients with breast cancer followed at Limoges University Hospital. The optimal cut-off for high Ki67 expression (Ki67hi) was established as 20%. The threshold for uPA and PAI-1 positivity was 3 ng/mg and 14 ng/mg, respectively. RESULTS: Ki67 expression was lower in uPA/PAI-1-negative than in uPA/PAI-1-positive tumours (227 tumours; P = 0.04). The addition of Ki67 status to the St. Gallen criteria resulted in a 28% increase in the rate of identification of high-risk tumours with a potential indication for chemotherapy (P < 0.001). When considering uPA/PAI-1 levels together with the St Gallen criteria (including Ki67 expression), the number of cases identified as having a high recurrence risk with a potential indication for adjuvant chemotherapy increased by 20% (P < 0.001). Adjuvant chemotherapy was 9% less likely to be recommended by a multidisciplinary board when using the current criteria compared with using a combination of the St. Gallen criteria and Ki67 and uPA/PAI-1 status (P = 0.03). CONCLUSIONS: Taken together, our data show discordance among markers in identifying the risk of recurrence, even though each marker may prove to be independently valid.

Common variants in glucuronidation enzymes and membrane transporters as potential risk factors for colorectal cancer: a case control study.

BACKGROUND: Associations between polymorphisms of UDP-glucuronosyltransferases (UGTs) or efflux transporters (e.g., P-glycoprotein and MRP2) and different types of cancer have been described, whereas the role of influx transporters (e.g. OATP1B1 and OATP2B1) has been seldom explored. The GenColon study investigated potential associations between variant alleles of UGTs, efflux and influx transporters and CRC. METHODS: Three hundred CRC cases were matched with 300 controls for age, sex and enrolment site. Fifteen SNPs in UGT1A6-9, UGT2B7, ABCB1, ABCC2, SLCO1B1 and SLCO2B1 genes were characterized using Taqman® PCR. Using multivariate conditional logistic regression, we investigated the relationships between CRC and "environmental" risk factors (physical activity, housing and working areas, consumption of red meat, tobacco, alcohol); genetic polymorphisms, in the study population and in the subgroups with "environmental" risk factors. RESULTS: No significant association was observed for the analyzed SNPs (or haplotypes). However, an increased CRC risk was found in carriers of the UGT1A8 rs1042597-G variant allele (additive risk OR = 3.39[1.29-8.89], p = 0.02951) in the subgroup of meat-consumers (n = 84), and in carriers of the ABCB1 rs1045642-T (exon26) variant allele (additive risk; OR = 1.89[1.10-3.39], p = 0.0257) in the "never alcohol consumption subgroup" (n = 125). In addition, as previously reported, the following CRC risk factors were identified: absence of physical activity (OR = 6.35[3.70-10.9], p < 0.0001), living or working in rural or mix area (OR = 2.50[1.48-4.23], p = 0.0006 and OR = 2.99[1.63-5.48], p = 0.004, respectively) and tobacco exposure >30 years (3.37[1.63-6.96], p = 0.0010). CONCLUSIONS: Variant genotypes of influx transporters (OATP1B1 and 2B1) were not associated with CRC. This study confirmed the influence of lifestyle factors, but not the previously reported detrimental effect of SNPs in intestinal UGTs or efflux transporters, except for a UGT1A8 variant in subjects consuming meat and the exon 26 SNP of ABCB1 in the never alcohol consumption subgroup. TRIAL REGISTRATION: Registered in Direction Générale de la Santé the 1st July 2008 under the number DGS2008-0144.

Towards therapeutic drug monitoring of everolimus in cancer? Results of an exploratory study of exposure-effect relationship.

INTRODUCTION: Therapeutic drug monitoring (TDM) of everolimus is not performed in oncology and no trough level (C0) target has been yet defined. The aim of this study was to determine everolimus C0 target for toxicity and efficacy. MATERIALS AND METHODS: Clinical, biological and radiologic data from 54 patients were collected. Toxicity event was defined by termination, temporary interruption and/or dose reduction of everolimus while efficacy was defined as progression-free survival. C0 values were dichotomized by ROC curve analysis and the association between exposure and outcome was determined using Cox models for repeated events (toxicity) or Cox model censured at the first event (progression free survival). RESULTS: Among the 42 patients (77.8%) with breast cancer, 10 (18.5%) kidney cancer and 2 (3.7%) neuroendocrine cancer, adverse events were reported in 75.9% of the patients (everolimus termination in 25.9% patients). C0 everolimus higher than 26.3ng/mL (Sen=0.38,Spe=0.88) were associated with a 4-fold increased risk of toxicity (HR=4.12, IC95%=[1.48-11.5], p=0.0067) whereas C0 lower than 11.9ng/mL were associated with a 3-fold increased risk of progression (HR=3.2, IC95%=[1.33-7.81],p=0.001). DISCUSSION: Further studies are required to evaluate the everolimus C0 threshold proposed for toxicity (26.3ng/mL) and for progression (11.9ng/mL) especially with a large number of patients and more homogeneous types of cancer. However, these results are in favour of TDM for everolimus in oncology.

Chemotherapy outcome predictive effectiveness by the Oncogramme: pilot trial on stage-IV colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) remains a major public concern. While conventional chemotherapeutic regimens have proved useful against advanced/metastatic diseases, progresses are to be made to effectively cure the large portion of patients not benefiting from these treatments. One direction to improve response rates is to develop chemosensitivity and resistance assays (CSRAs) efficiently assisting clinicians in treatment selection process, an already long preoccupation of oncologists and researchers. Several methods have been described to this day, none achieving yet sufficient reliability for recommended use in the clinical routine. METHODS: We led a pilot study on 19 metastatic CRC patients evaluating capacity of the Oncogramme, a standardized process using tumor ex vivo models, to provide chemosensitivity profiles and predict clinical outcome of patients receiving standard CRC chemotherapeutics. Oncogramme responses were categorized according to the method of percentiles to assess sensitivity, specificity and concordance. RESULTS: We report from a primary analysis a success rate of 97.4 %, a very good sensitivity (84.6 %), a below-average specificity (33.3 %), along with a global agreement of 63.6 % and a concordance between Oncogramme results and patients' responses (Kappa coefficient) of 0.193. A supplementary analysis, focusing on CRC patients with no treatment switch over a longer time course, demonstrated improvement in specificity and concordance. CONCLUSIONS: Results establish feasibility and usefulness of the Oncogramme, prelude to a larger-scale trial. Advantages and drawbacks of the procedure are discussed, as well as the place of CSRAs within the future arsenal of methods available to clinicians to individualize treatments and improve patient prognosis. TRIAL REGISTRATION: ClinicalTrials.gov database, registration number: NCT02305368.

Bevacizumab with or without erlotinib as maintenance therapy in patients with metastatic colorectal cancer (GERCOR DREAM; OPTIMOX3): a randomised, open-label, phase 3 trial.

BACKGROUND: The combination of an anti-VEGF or an anti-EGFR-targeted monoclonal antibody with chemotherapy has shown clinical activity in patients with metastatic colorectal cancer. However, combining both anti-VEGF and anti-EGFR antibodies with chemotherapy in first-line treatment resulted in adverse outcomes. We assessed whether the combination of erlotinib, an EGFR tyrosine kinase inhibitor, with bevacizumab could increase the efficacy of maintenance therapy in patients with unresectable metastatic colorectal cancer. METHODS: This randomised, open-label, phase 3 study was undertaken in 49 centres in France, Austria, and Canada. Eligible patients were aged 18-80 years with histologically confirmed, unresectable metastatic colorectal cancer, WHO performance status 0-2, had received no previous therapy for metastatic disease, and had adequate organ function. Patients without disease progression after bevacizumab-based induction therapy were randomly assigned (1:1) by a minimisation technique to bevacizumab (7·5 mg/kg every 3 weeks) or bevacizumab plus erlotinib (150 mg once daily) as maintenance therapy until progression. All patients were stratified by centre, baseline performance status, age, and number of metastatic sites. The primary endpoint was progression-free survival on maintenance therapy analysed by intention to treat. We report the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00265824. FINDINGS: Between Jan 1, 2007, and Oct 13, 2011, 700 eligible patients were enrolled; following induction treatment, patients without disease progression were randomly assigned to bevacizumab (n=228) or bevacizumab plus erlotinib (n=224). At the final analysis, median follow-up was 51·0 months (IQR 36·0-60·0) in the bevacizumab group and 48·3 months (31·5-61·0) in the bevacizumab plus erlotinib group. In the primary analysis (after 231 progression-free survival events), median progression-free survival from randomisation was 5·1 months (95% CI 4·1-5·9) in the bevacizumab plus erlotinib group compared with 6·0 months (4·6-7·9) in the bevacizumab group (stratified hazard ratio [HR] 0·79 [95% CI 0·60-1·06]; p=0·11; unstratified HR 0·76 [0·59-0·99]; p=0·043). In the final analysis, median progression-free survival from randomisation was 5·4 months (95% CI 4·3-6·2) in the bevacizumab plus erlotinib group compared with 4·9 months (4·1-5·7) in the bevacizumab group (stratified HR 0·81 [95% CI 0·66-1·01], p=0·059; unstratified HR 0·78 [0·68-0·96], p=0·019). At the final analysis, median overall survival from maintenance was 24·9 months (95% CI 21·4-28·9) in the bevacizumab plus erlotinib group and 22·1 months (19·6-26·7) in the bevacizumab group (stratified HR 0·79 [95% CI 0·63-0·99], p=0·036; unstratified HR 0·79 [0·64-0·98], p=0·035). The most frequent grade 3-4 adverse events were skin rash (47 [21%] of 220 patients in the bevacizumab plus erlotinib group vs none of 224 patients in the bevacizumab alone group), diarrhoea (21 [10%] vs two [<1%]), and asthenia (12 [5%] vs two [<1%]). INTERPRETATION: Maintenance bevacizumab plus erlotinib might be a new non-chemotherapy-based maintenance option for the first-line treatment of patients with unresectable metastatic colorectal cancer after bevacizumab-based induction therapy. FUNDING: GERCOR and F Hoffmann-La Roche.

Clinical benefits of non-taxane chemotherapies in unselected patients with symptomatic metastatic castration-resistant prostate cancer after docetaxel: the GETUG-P02 study.

OBJECTIVE: To evaluate the overall benefits of non-taxane chemotherapies in a non-selected population including unfit patients presenting with symptoms and pain. PATIENTS AND METHODS: This randomized phase II study reports data from 92 patients (52% >70 years old; 40% with a performance score of 2) previously treated with taxane-based chemotherapy, collected from 15 centres in France. Patients received i.v. mitoxantrone (MTX), oral vinorelbine, or oral etoposide, together with oral prednisone. Palliative benefit (pain response without progression of the disease), biological and tumoural responses, and toxicity profile as well as geriatric assessment (in elderly population) were analysed on an intention-to-treat basis. RESULTS: The palliative response rate was 17% for the whole population, and reached 29% when considering the MTX arm. Pain control was achieved in 40% of the patients. The median overall survival was 10.4 months, and was longer in palliative responders. Few grade 3-4 toxicities were observed. The subgroup analysis of elderly patients showed similar results regarding the number and dose intensity of treatments, efficacy and safety. CONCLUSION: In a population including frail and/or elderly patients, who are poorly represented in most clinical studies, non-taxane chemotherapy may remain a relevant option for metastatic prostate cancer having relapsed after a docetaxel-based regimen. Although new treatment options are now approved, the decision-making process should take into account their expected benefit/risk ratio based on the patient status.

6 months versus 12 months of adjuvant trastuzumab for patients with HER2-positive early breast cancer (PHARE): a randomised phase 3 trial.

BACKGROUND: Since 2005, 12 months of adjuvant trastuzumab has been the standard treatment for patients with HER2-positive early-stage breast cancer. However, the optimum duration of treatment has been debated. We did a non-inferiority trial of a shorter exposure of 6 months versus the standard 12 months of trastuzumab for patients with early breast cancer. METHODS: We did an open-label, randomised, phase 3 trial in 156 centres in France. Patients with HER2-positive early breast cancer who had received at least four cycles of chemotherapy, had breast-axillary surgery, and had received up to 6 months of trastuzumab (administered by intravenous infusions over 30-90 min every 3 weeks; initial loading dose 8 mg/kg; 6 mg/kg thereafter) before randomisation were eligible. Patients were randomly assigned via central randomisation procedure with web-based software to continue trastuzumab for another 6 months (12 months total duration; control group) or to discontinue trastuzumab at 6 months (6 months total duration; experimental group). Randomisation was stratified by concomitant or sequential administration of trastuzumab with chemotherapy, oestrogen-receptor status, and centre using a minimisation algorithm. The primary endpoint was disease-free survival, with a prespecified non-inferiority margin of 1·15. Analyses were done in the intention-to-treat population. This study is registered at ClinicalTrials.gov, number NCT00381901. FINDINGS: 1691 patients were randomly assigned to receive 12 months of trastuzumab and 1693 to receive 6 months of trastuzumab; 1690 patients in each group were included in the intention-to-treat analyses. After a median follow-up of 42·5 months (IQR 30·1-51·6), 175 disease-free survival events were noted in the 12-month group and 219 in the 6-month group. 2-year disease-free survival was 93·8% (95% CI 92·6-94·9) in the 12-month group and 91·1% (89·7-92·4) in the 6-month group (hazard ratio 1·28, 95% CI 1·05-1·56; p=0·29). 119 (93%) of the 128 cardiac events (clinical or based on assessment of left ventricular ejection fraction) occurred while patients were receiving trastuzumab. Significantly more patients in the 12-month group experienced a cardiac event than did those in the 6-month group (96 [5·7%] of 1690 patients vs 32 [1·9%] of 1690 patients, p<0·0001). INTERPRETATION: After 3·5 years follow-up, we failed to show that 6 months of treatment with trastuzumab was non-inferior to 12 months of trastuzumab. Despite the higher rates of cardiac events, 12 months of adjuvant trastuzmab should remain the standard of care. FUNDING: French National Cancer Institute.

Patient Identification and Tumor Identification Management: Quality Program in a Cancer Multicentric Clinical Data Warehouse.

Background: The Regional Basis of Solid Tumor (RBST), a clinical data warehouse, centralizes information related to cancer patient care in 5 health establishments in 2 French departments. Purpose: To develop algorithms matching heterogeneous data to "real" patients and "real" tumors with respect to patient identification (PI) and tumor identification (TI). Methods: A graph database programed in java Neo4j was used to build the RBST with data from ~20 000 patients. The PI algorithm using the Levenshtein distance was based on the regulatory criteria identifying a patient. A TI algorithm was built on 6 characteristics: tumor location and laterality, date of diagnosis, histology, primary and metastatic status. Given the heterogeneous nature and semantics of the collected data, the creation of repositories (organ, synonym, and histology repositories) was required. The TI algorithm used the Dice coefficient to match tumors. Results: Patients matched if there was complete agreement of the given name, surname, sex, and date/month/year of birth. These parameters were assigned weights of 28%, 28%, 21%, and 23% (with 18% for year, 2.5% for month, and 2.5% for day), respectively. The algorithm had a sensitivity of 99.69% (95% confidence interval [CI] [98.89%, 99.96%]) and a specificity of 100% (95% CI [99.72%, 100%]). The TI algorithm used repositories, weights were assigned to the diagnosis date and associated organ (37.5% and 37.5%, respectively), laterality (16%) histology (5%), and metastatic status (4%). This algorithm had a sensitivity of 71% (95% CI [62.68%, 78.25%]) and a specificity of 100% (95% CI [94.31%, 100%]). Conclusion: The RBST encompasses 2 quality controls: PI and TI. It facilitates the implementation of transversal structuring and assessments of the performance of the provided care.

Ki-67: level of evidence and methodological considerations for its role in the clinical management of breast cancer: analytical and critical review.

Clinicians can use biomarkers to guide therapeutic decisions in estrogen receptor positive (ER+) breast cancer. One such biomarker is cellular proliferation as evaluated by Ki-67. This biomarker has been extensively studied and is easily assayed by histopathologists but it is not currently accepted as a standard. This review focuses on its prognostic and predictive value, and on methodological considerations for its measurement and the cut-points used for treatment decision. Data describing study design, patients' characteristics, methods used and results were extracted from papers published between January 1990 and July 2010. In addition, the studies were assessed using the REMARK tool. Ki-67 is an independent prognostic factor for disease-free survival (HR 1.05-1.72) in multivariate analyses studies using samples from randomized clinical trials with secondary central analysis of the biomarker. The level of evidence (LOE) was judged to be I-B with the recently revised definition of Simon. However, standardization of the techniques and scoring methods are needed for the integration of this biomarker in everyday practice. Ki-67 was not found to be predictive for long-term follow-up after chemotherapy. Nevertheless, high KI-67 was found to be associated with immediate pathological complete response in the neoadjuvant setting, with an LOE of II-B. The REMARK score improved over time (with a range of 6-13/20 vs. 10-18/20, before and after 2005, respectively). KI-67 could be considered as a prognostic biomarker for therapeutic decision. It is assessed with a simple assay that could be standardized. However, international guidelines are needed for routine clinical use.

Can the Six-Minute Walk Test Be Used to Individualize Physical Activity Intensity in Patients with Breast Cancer?

BACKGROUND: Adapted physical activity (APA) aids breast cancer patients. It is necessary to use an adapted target heart rate (HR) when prescribing exercise intensity. METHODS: In total, 138 patients previously included in two published randomized clinical trials underwent the CPET and 6MWT before and after adjuvant therapy. Of these patients, 85 had performed APA, and 53 had received only the usual therapy. HRs were recorded during the two tests. RESULTS: Before starting chemotherapy, good agreement (intraclass correlation (ICC) 0.69; confidence interval at 95% IC0.95 (0.591-0.769); p < 0.001) and a moderate correlation were evident between the 6MWT-HR and ventilatory threshold HR of the CPET (r = 0.70; p < 0.001). Good agreement and a high positive correlation were noted only in the group who engaged in APA (ICC 0.77; IC0.95 (0.659-0.848); p < 0.001; r = 0.8; p < 0.01); moderate agreement and a moderate positive correlation were apparent in the control group (ICC 0.57; IC0.95 (0.329-0.74); p < 0.001; r = 0.6; p < 0.01). The correlations were independent of age and body mass index. CONCLUSIONS: The 6MWT-HR can be used to prescribe exercise intensity for breast cancer patients both before and after specific treatment with concomitant APA.

Population pharmacokinetic model of irinotecan and its four main metabolites in patients treated with FOLFIRI or FOLFIRINOX regimen.

PURPOSE: The aim of the present study was to characterize the pharmacokinetics of irinotecan and its four main metabolites (SN-38, SN-38G, APC and NPC) in metastatic colorectal cancer patients treated with FOLFIRI and FOLFIRINOX regimens and to quantify and explain the inter-individual pharmacokinetic variability in this context. METHODS: A multicenter study including 109 metastatic colorectal cancer patients treated with FOLFIRI or FOLFIRINOX regimen, associated or not with a monoclonal antibody, was conducted. Concentrations of irinotecan and its four main metabolites were measured in 506 blood samples during the first cycle of treatment. Collected data were analyzed using the population approach. First, fixed and random effects models were selected using statistical and graphical methods; second, the impact of covariates on pharmacokinetic parameters was evaluated to explain the inter-individual variability in pharmacokinetic parameters. RESULTS: A seven-compartment model best described the pharmacokinetics of irinotecan and its four main metabolites. First-order rates were assigned to distribution, elimination, and metabolism processes, except for the transformation of irinotecan to NPC which was nonlinear. Addition of a direct conversion of NPC into SN-38 significantly improved the model. Co-administration of oxaliplatin significantly modified the distribution of SN-38. CONCLUSION: To our knowledge, the present model is the first to allow a simultaneous description of irinotecan pharmacokinetics and of its four main metabolites. Moreover, a direct conversion of NPC into SN-38 had never been described before in a population pharmacokinetic model of irinotecan. The model will be useful to develop pharmacokinetic-pharmacodynamic models relating SN-38 concentrations to efficacy and digestive toxicities. CLINICAL TRIALS REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT00559676.

Comparison of 18FDG-PET/CT and conventional follow-up methods in colorectal cancer: A randomised prospective study.

BACKGROUND: A surveillance program was performed in colorectal cancer (CRC) patients after surgery, to diagnose asymptomatic recurrence. AIMS: To assess whether 18-FDG positron emission tomography/CT (PET/CT) improved the detection of recurrence during a 3-year follow-up. METHODS: A multicentre, two-arm randomised prospective trial comparing different 36-month follow-up strategies. Complete colonoscopy was performed at baseline and after 3 years and clinical exams with imaging every 3 months. The conventional arm (A) received carcinoembryonic antigen, liver echography, and alternated between lung radiography and computed tomography (CT) scans. The experimental arm (B) received PET/CT. RESULTS: A total of 365 patients with colon (79.4%) or rectal cancer (20.6%), stages II (48.2%) or III (50.8%), were enroled in this study. At 36 months, intention-to-treat analysis revealed recurrence in 31 (17.2%) patients in arm A and 47 (25.4%) in arm B (p = 0.063). At 3 years, 7 of 31 relapses (22.5%) in arm A were surgically treated with curative intent, compared to 17 of 47 (36.2%) in arm B (p = 0.25). The rates of recurrence and new cancers were higher in arm B than arm A (p = 0.038). CONCLUSIONS: PET/CT follow-up every 6 months did not increase the rate of recurrence at 3 years or the rate of surgically treated recurrence compared with conventional follow-up.

Impact of Body Composition in Overweight and Obese Patients With Localised Renal Cell Carcinoma.

BACKGROUND/AIM: To investigate the impact of body composition on morbidity and mortality at the initial diagnosis of localised renal cell carcinoma (RCC) in patients with overweight or obesity. PATIENTS AND METHODS: Sarcopenia was defined using sex-specific cut-off points and other body composition parameters by median values with computed tomography imaging. RESULTS: Among the 96 patients, 40 had sarcopenia (43.0%) at diagnosis. Body composition had no effect on morbidity and 5-year disease-free survival contrary to the classic factors (p<0.05). In the subgroup of obese patients, those with sarcopenia had a poor prognosis (p=0.04) but not in the population with overweight (p=0.9). CONCLUSION: Sarcopenia was frequently associated with localised RCC at the initial diagnosis. Body composition did not affect morbidity or outcomes. BMI was involved in morbidity and there was paradoxically longer survival in the obesity group.

[High fidelity simulation training for medical oncology announcement consultation]. / Simulation haute-fidélité à la consultation d'annonce en oncologie médicale.

INTRODUCTION: Medical oncology bad news consultation is a particularly stressful situation for both the patient and the physician. High-fidelity simulation is a learning option that has never been evaluated in France in this field. MATERIALS AND METHODS: This is a feedback from simulated announcement consultations carried out from January 2018 to May 2019. Residents from the medical oncology and radiotherapy departments performed high-fidelity simulations at the announcement consultation with an announcement nurse, a psychologist, a certified coach and an oncologist. A competency assessment was completed in pre-test, immediate post-test and after 5 months. RESULTS: Fourteen of the 16 eligible interns participated. The pre-test competency assessment showed that interns over 5 semesters reported being more comfortable at the consultation (P=0.04) and thought they were clearly explaining the disease (P=0.03). However, all residents, regardless of the semester, felt stressed before a consultation. The evolution of parameters skills after the simulation was positive for all criteria, particularly for adaptation to patient reactions, use of appropriate vocabulary and reduction of stress (P<0.05). This evolution was independent of the gender, curriculum, semester, or previous completion of a medical oncology internship. More than 80% of the students were ready to repeat this type of training. CONCLUSION: This training demonstrates the value of simulation training for medical oncology advertising consultation.

Home-Based Physical Activity in Patients With Breast Cancer: During and/or After Chemotherapy? Impact on Cardiorespiratory Fitness. A 3-Arm Randomized Controlled Trial (APAC).

OBJECTIVES: Physical activity (PA) programs are recommended for breast cancer care. However, their modalities remain to be discussed. This study determined the best time to begin a personalized or adapted program based on cardiopulmonary exercise test function. This randomized controlled trial evaluated the effect of home-based adapted PA (APA) performed during or after treatment on cardiorespiratory fitness (CRF) at 12 months. METHOD: The primary endpoint was the peak oxygen consumption (VO2peak) at 12 months (group A vs C and B vs C). Secondary endpoints included the 6-minute walking test, assessment of muscle strength, fatigue, quality of life, anxiety, and depression, and a questionnaire on PA levels. All tests were evaluated at baseline and at 6 and 12 months. A total of 94 patients with breast cancer were randomized to 3 different groups: group A, performing 6 months of APA during adjuvant care; group B, 6 months of APA after adjuvant care; and group C, 12 months of APA during and after specific care. The program combined 1 resistance session and 2 aerobic sessions per week. Analysis of variance was used for repeated measures, Student's t-test or the Mann-Whitney U-test for continuous variables, and χ2 test for binary or categorical variables. RESULTS: The study assessed 81 participants at 6 months and 73 at 12 months. The majority of patients completed more than 85% of the exercise sessions. The baseline for VO2peak and secondary outcomes did not differ among the groups. VO2peak increased during the exercise period and decreased during the chemotherapy period without APA, but at 12 months no significant difference was observed. The same variation was observed in the 6-minute walking test, with significance at 6 months between A+C versus B (P = .04), but no difference among the groups at 12 months. In the 3 groups, no decreases in other studied parameters were noted, except at 6 months in group B without APA. CONCLUSION: Home-based APA in breast cancer patients has a positive effect on CRF and physical functions, with no differences based on the timing of this program based on specific cancer treatment. TRIAL REGISTRATION: ClinicalTrials.gouv.fr (NCT01795612). Registered 20 February 2013.

Prospective evaluation of an anti-cancer drugs management programme in a dedicated oral therapy center (DICTO programme).

Oral therapies have highly modified cancer patient management and changed hospital practises. We introduce a specific Oral Therapy Centre and retrospectively review information prospectively recorded by co-ordination nurses (CNs) (the DICTO programme). We describe the roles played by CNs in the management of oral cancer therapies at Limoges Dupuytren Hospital between May 2015 and June 2018. All cancers, irrespective of stage or whether oral general chemotherapy or targeted therapy was prescribed, are included. We followed up 287 patients of median age 67 years (range 26-89 years). Of these, 76% had metastases and 44% were on first-line therapy. The vast majority (88%) of their first CN contacts occurred just after physician consultation and lasted an average of 60 min. As part of follow-up, the CNs made 2719 calls (average 10 min) to patients to educate them and to verify compliance and drug tolerance. They also received 833 calls from patients (70%) or their relatives or health professionals (30%) seeking advice on management of side effects. In addition to the initial appointments, 1069 non-scheduled follow-up visits were made to assess side effects (49.2%). The CNs devoted 5 h to each patient over 3 months of treatment (i.e. 25 min/day) and, also organised scheduled hospitalisations in the department of oncology for 51% of patients. We show the interest and real-life work in a specific oral therapy centre within oncology department with the role of CNs to facilitate the global health care of the patients.

Cardiac toxicity with capecitabine, vinorelbine and trastuzumab therapy: case report and review of fluoropyrimidine-related cardiotoxicity.

A 45-year-old woman presented with a metastatic breast carcinoma and was treated with capecitabine, oral vinorelbine and trastuzumab combination therapy. The initial echocardiogram and the ECG were considered normal. She began treatment with 3-weekly cycles of the combination therapy. After the fourth dose of capecitabine, she presented with severe chest and arm pain, which was responsive to nitroglycerine spray. ECG at admission demonstrated tachycardia with ST-segment elevation suggesting ischemia. The clinical symptoms returned to baseline after a few hours and within 24 h the ECG showed inverted T in leads V3-V6. Cardiac ultrasonography revealed hypokinesia in the left ventricle without segmentary hypokinesia, with mildly reduced global systolic function, which normalized 1 week later. Two weeks later, she was rechallenged with capecitabine. After the fourth dose, the patient developed chest pain. ECG showed infero-apico-lateral injury, which normalized after administration of nitrates, nicorandil and verapamil and discontinuation of capecitabine. This case suggests that capecitabine can lead to the cardiotoxicity characteristic of other fluoropyrimidines. Therefore, it is important to inform patients about the risk of angina-like chest pain, to stop treatment immediately if symptoms occur, and to monitor the patient in hospital. Fluoropyrimidine rechallenge should be avoided because of the risk of ischemic event or sudden death.

First validation of the G-8 geriatric screening tool in older patients with glioblastoma.

INTRODUCTION: Management of glioblastoma, with a very poor prognosis, remains a challenge in older patients because of coexisting comorbidities and the increased risk of toxic treatment effects. The use of screening tools to identify vulnerable patients is essential. This study was performed to establish whether the G8 scale can be used for screening older patients with glioblastoma. METHODS: We retrospectively reviewed the files of patients assessed by the G8 scale and diagnosed with glioblastoma at a single center from January 2010 to July 2017. Patients aged 65 years or older were classified into three groups (more efficiently than two groups) according to their G8 score to identify those with a poor prognosis: high score group, G8 score 14.5-17; intermediate score group, G8 score 10.5-14; and low score group, G8 score < 10.5. RESULTS: Of 89 patients, 19% were classified into the high score group, 43% into the intermediate score group, and 38% into the low score group. Median overall survival was four months in the low score group, 15 months in the intermediate score group, and 42 months in the high score group (p < .0001). On multivariate analysis, G8 score was a significant independent predictor of overall survival (hazard ratio: 55.46; 99.5% confidence interval: 13.42-229.13; p < .0001). CONCLUSIONS: Here, we highlighted the possibility of using the G8 score, with possibly three cut-offs, in the management of older patients with glioblastoma and determined the prognostic role of this quick and easy screening tool.

Comparative Study of Neoadjuvant Chemotherapy With and Without Zometa for Management of Locally Advanced Breast Cancer With Serum VEGF as Primary Endpoint: The NEOZOL Study.

INTRODUCTION: Neoadjuvant chemotherapy has become the treatment of choice for locally advanced breast cancer. Zoledronic acid (ZA) is a bisphosphonate initially used in the treatment of bone metastases because of its antibone resorption effect. Antitumor effects of ZA, including the inhibition of cell adhesion to mineralized bone or the antiangiogenic effect, have been demonstrated. However, the clinical significance of these effects remains to be determined. MATERIALS AND METHODS: We undertook a multicenter open-label randomized trial to analyze the value of adding ZA to neoadjuvant chemotherapy for TNM clinical stage T2/T3 breast cancer. The primary endpoint was the evolution of serum VEGF. RESULTS: The data from 24 patients were included in the ZA group and 26 in the control group. The evolution of serum VEGF was slightly in favor of ZA at 5.5 months (-0.7% vs. +7.5%), without reaching statistical significance (P = .52). The secondary endpoints were the breast conservation rate (higher with ZA; 83.3% vs. 65.4%; P = NS), pathologic complete response (no effect), and circulating tumor cells (odds ratio, 0.68 in favor of ZA; 95% confidence interval, 0.02-24.36). No cases of jaw necrosis or severe renal failure were observed in either group. CONCLUSION: ZA is an antitumor drug of interest because of its multiple effects on tumor biology. Larger trials with longer follow-up that include additional endpoints such as relapse and survival rates would be of interest.