Baseline quality of life and chemotherapy toxicities in patients with early breast cancer.

BACKGROUND: The authors used the French breast cancer Cancer and Toxicities (CANTO) cohort to study the associations between baseline quality of life and chemotherapy dose-reductions (CDRs) or postchemotherapy-toxicities (PCTs). METHODS: In total, 3079 patients with breast cancer who received chemotherapy were included in this analysis. The associations between baseline physical functioning (PF) and fatigue measured using the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30, and two endpoints-CDRs during adjuvant or neoadjuvant chemotherapy; and selected PCTs were estimated with odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) using logistic regression models. RESULTS: Among the 3079 patients from the CANTO cohort who were included, 718 (33.0%) received chemotherapy in the neoadjuvant setting, and 2361 (67.0%) received chemotherapy as adjuvant treatment. The chemotherapy included taxanes in 94.2% of patients and anthracyclines in 90.5% of patients. Overall, 15.5% of patients experienced CDRs and, 31.0% developed PCTs. Women with low baseline PF scores (<83) had higher multivariate odds of developing CDRs compared with those who had PF scores ≥83 (OR, 1.54; 95% CI, 1.13-2.09). The corresponding OR for PCTs was 1.50 (95% CI, 1.13-2.00). Women with high baseline fatigue scores had higher odds of CDRs (OR, 1.43; 95% CI, 1.13-1.76) and PCTs (OR, 1.32; 95% CI, 1.10-1.59). CONCLUSIONS: By using the national CANTO cohort, baseline PF and fatigue were independently associated with CDRs and PCTs.

Uptake of Recommendations for Posttreatment Cancer-Related Fatigue Among Breast Cancer Survivors.

BACKGROUND: Physical activity (PA) and psychosocial interventions are recommended management strategies for cancer-related fatigue (CRF). Randomized trials support the use of mind-body techniques, whereas no data show benefit for homeopathy or naturopathy. METHODS: We used data from CANTO (ClinicalTrials.gov identifier: NCT01993498), a multicenter, prospective study of stage I-III breast cancer (BC). CRF, evaluated after primary treatment completion using the EORTC QLQ-C30 (global CRF) and QLQ-FA12 (physical, emotional, and cognitive dimensions), served as the independent variable (severe [score of ≥40/100] vs nonsevere). Outcomes of interest were adherence to PA recommendations (≥10 metabolic equivalent of task [MET] h/week [GPAQ-16]) and participation in consultations with a psychologist, psychiatrist, acupuncturist, or other complementary and alternative medicine (CAM) practitioner (homeopath and/or naturopath) after CRF assessment. Multivariable logistic regression examined associations between CRF and outcomes, adjusting for sociodemographic, psychologic, tumor, and treatment characteristics. RESULTS: Among 7,902 women diagnosed from 2012 through 2017, 36.4% reported severe global CRF, and 35.8%, 22.6%, and 14.1% reported severe physical, emotional, and cognitive CRF, respectively. Patients reporting severe global CRF were less likely to adhere to PA recommendations (60.4% vs 66.7%; adjusted odds ratio [aOR], 0.82; 95% CI, 0.71-0.94; P=.004), and slightly more likely to see a psychologist (13.8% vs 7.5%; aOR, 1.29; 95% CI, 1.05-1.58; P=.014), psychiatrist (10.4% vs 5.0%; aOR, 1.39; 95% CI, 1.10-1.76; P=.0064), acupuncturist (9.8% vs 6.5%; aOR, 1.46; 95% CI, 1.17-1.82; P=.0008), or CAM practitioner (12.5% vs 8.2%; aOR, 1.49; 95% CI, 1.23-1.82; P<.0001). There were differences in recommendation uptake by CRF dimension, including that severe physical CRF was associated with lower adherence to PA (aOR, 0.74; 95% CI, 0.63-0.86; P=.0001) and severe emotional CRF was associated with higher likelihood of psychologic consultations (aOR, 1.37; 95% CI, 1.06-1.79; P=.017). CONCLUSIONS: Uptake of recommendations to improve CRF, including adequate PA and use of psychosocial services, seemed suboptimal among patients with early-stage BC, whereas there was a nonnegligible interest in homeopathy and naturopathy. Findings of this large study indicate the need to implement recommendations for managing CRF in clinical practice.

Unhealthy behaviors after breast cancer: Capitalizing on a teachable moment to promote lifestyle improvements.

BACKGROUND: This study assessed the prevalence and risk factors of unhealthy behaviors among survivors of early-stage breast cancer. METHODS: Women (n = 9556) from the CANcer TOxicity cohort (NCT01993498) were included. Physical activity (PA), tobacco and alcohol consumption, and body mass index were assessed at diagnosis and at years 1 and 2 after diagnosis. A behavior was defined as unhealthy if patients failed to meet PA recommendations (≥10 metabolic equivalent task hours per week), reduce/quit tobacco, or decrease alcohol consumption to less than daily, or if they gained substantial weight over time. Multivariable-adjusted generalized estimating equations explored associations with unhealthy behaviors. RESULTS: At diagnosis, 41.7% of patients were inactive, 18.2% currently used tobacco, 14.6% consumed alcohol daily, and 48.9% were overweight or obese. At years 1 and 2, unhealthy PA behavior was reported among 37.0% and 35.6% of patients, respectively, unhealthy tobacco use behavior was reported among 11.4% and 9.5%, respectively, and unhealthy alcohol behavior was reported among 13.1% and 12.6%, respectively. In comparison with the previous assessment, 9.4% and 5.9% of underweight and normal-weight patients had transitioned to the overweight or obese category at years 1 and 2, respectively, and 15.4% and 16.2% of overweight and obese patients had gained ≥5% of their weight at years 1 and 2, respectively. One in 3 current tobacco smokers and 1 in 10 daily alcohol users reported improved behaviors after diagnosis. Older women (5-year increment) were more likely to be inactive (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 1.01-1.05) and report unhealthy alcohol behavior (aOR, 1.28; 95% CI, 1.23-1.33) but were less likely to engage in unhealthy tobacco use (aOR, 0.81; 95% CI, 0.78-0.85). Being at risk for depression (vs not being at risk for depression) was associated with reduced odds of unhealthy tobacco use (aOR, 0.67; 95% CI, 0.46-0.97) and with a higher likelihood of unhealthy alcohol behavior (aOR, 1.58; 95% CI, 1.14-2.19). Women with a college education (vs a primary school education) less frequently reported an unhealthy PA behavior (aOR, 0.61; 95% CI, 0.51-0.73) and were more likely to report unhealthy alcohol behavior (aOR, 1.85; 95% CI, 1.37-2.49). Receipt of chemotherapy (vs not receiving chemotherapy) was associated with higher odds of gaining weight (aOR, 1.51; 95% CI, 1.23-1.87) among those who were overweight or obese at diagnosis. CONCLUSIONS: The majority of women were adherent to healthy lifestyle behaviors at the time of their breast cancer diagnosis, but a significant subset was nonadherent. Unhealthy behaviors tended to persist after the breast cancer diagnosis, having varying clinical, psychological, sociodemographic, and treatment-related determinants. This study will inform more targeted interventions to promote optimal health.

"As du Coeur" study: a randomized controlled trial on physical activity maintenance in cardiovascular patients.

BACKGROUND: The benefits of supervised physical activity programs in cardiac rehabilitation have been amply demonstrated, but the quantity of physical activity often declines quickly once supervision ends. This trial assesses the effectiveness of an experimental intervention drawing on habit formation theory to maintain physical activity. METHODS: Cardiovascular patients (N = 47) were randomly assigned to one of two groups. The first group participated in two supervised physical activity (SPA) sessions per week for 20 weeks. The second group was offered a progressively autonomous physical activity (PAPA) program as follows: the same supervised program as the SPA group for 10 weeks and then a further 10 weeks with one supervised session replaced by a strategy to build and sustain the habit of autonomous physical activity. The International Physical Activity Questionnaire (IPAQ; Craig et al. Med Sci Sports Exerc 35(8):1381-1395, 2003) was used to measure the quantity of physical activity, which was the primary outcome. The number of participants was limited, and we thus took multiple IPAQ measurements (at 0, 5, 7, 9 and 12 months after the start of the intervention) and used a mixed model for analysis. Physical condition, automaticity of the physical activity behavior, motivation, and quality of life were examined for changes. RESULTS: No significant between-group differences were noted for physical activity behaviors after the program, physical condition, motivation, or behavioral automaticity. The PAPA group nevertheless completed more PA sessions during the intervention, and their quality of life was significantly higher than that of the SPA group at 12 months. CONCLUSION: Although the number of supervised sessions was lower, the progressively autonomous PA program resulted in the same or even higher positive outcomes than the fully supervised PA program. TRIAL REGISTRATION: Current Controlled Trials ISRCTN77313697 , retrospectively registered on 20 November 2015.

"As du Coeur" study: a randomized controlled trial on quality of life impact and cost effectiveness of a physical activity program in patients with cardiovascular disease.

BACKGROUND: Physical activity programs (PAP) in patients with cardiovascular disease require evidence of cost-utility. To assess improvement in health-related quality of life (QoL) and reduction of health care consumption of patients following PAP, a randomized trial was used. METHODS: Patients from a health insurance company who had experienced coronary artery disease or moderate heart failure were invited to participate (N = 1891). Positive responders (N = 50) were randomly assigned to a progressively autonomous physical activity (PAPA) program or to a standard supervised physical activity (SPA) program. The SPA group had two supervised sessions per week over 5 months. PAPA group had one session per week and support to aid habit formation (written tips, exercise program, phone call). To measure health-related quality of life EQ-5D utility score were used, before intervention, 6 months (T6) and 1 year later. Health care costs were provided from reimbursement databases. RESULTS: Mobility, usual activities and discomfort improved significantly in both group (T6). One year later, EQ-5D utility score was improved in the PAPA group only. Total health care consumption in the intervention group decreased, from a mean of 4097 euros per year before intervention to 2877 euros per year after (p = 0.05), compared to a health care consumption of 4087 euros and 4180 euros per year, in the total population of patients (N = 1891) from the health insurance company. The incremental cost effectiveness ratio was 10,928 euros per QALYs. CONCLUSION: A physical activity program is cost-effective in providing a better quality of life and reducing health care consumption in cardiovascular patients. TRIAL REGISTRATION: ISRCTN77313697 , retrospectively registered on 20 November 2015.

The influence of external stimulation in missing knowledge retrieval.

We investigated the effects of sensory reduction on the retrieval of information during tip-of-the-tongue (TOT) experiences. As conscious access results from severe competition in which external stimuli often have priority, we hypothesised that reducing external stimulation would allow individuals greater access to weakly activated inner knowledge. In Study 1, when participants experienced a TOT while answering a general knowledge question, they were given additional time to find the solution in a restricted (eyes closed + silence) or a non-restricted (eyes open + ambient noise) external stimulation environment. Results indicated that knowledge was more often retrieved when external stimulation was restricted than when not restricted. This result was replicated in a second study. Using an independent manipulation of the level of auditory and visual stimulation, Study 2 also indicated that the presence of visual stimulation was more disruptive for TOT resolution than the presence of auditory stimulation. Overall, the findings suggest that sensory restriction (especially of visual stimuli) facilitates the retrieval of weakly accessible knowledge through a greater processing of inner stimuli.

Impact of post-brentuximab vedotin consolidation on relapsed/refractory CD30+ Hodgkin lymphomas: a large retrospective study on 240 patients enrolled in the French Named-Patient Program.

Brentuximab vedotin was reported to be effective and safe against refractory/relapsed Hodgkin lymphoma in cohorts of between 12 to 102 patients. Herein we report our retrospective analysis of the French experience with brentuximab vedotin used alone to treat 240 refractory/relapsed Hodgkin lymphoma patients enrolled in a named patient program between 2011 and 2013. All patients had histologically documented CD30+ Hodgkin lymphoma; 74% had refractory disease or early relapses. After a median of 3 lines of chemotherapy, brentuximab vedotin was infused intravenously (1.8 mg/kg every 3 weeks). The primary endpoint was best response. Response at the end of treatment, its duration, survival data and toxicity profile were secondary endpoints. Patients received a median of 6 cycles; 68 underwent a consolidation thereafter. The best response was observed after a median of 4 cycles in 145 (60.4%) patients: 33.8% complete response/unconfirmed complete response, 26.7% partial response. Objective responses were observed as decreased (39.3%) in the 28 patients >60 years. The median response duration was 8.4 months. With median follow-up at 16.1 months, median progression-free survival was 6.8 months and this was significantly longer for patients transplanted after brentuximab vedotin (a median of 18,8 months); median overall survival was not reached. No death has been linked to brentuximab vedotin toxicity. The most common adverse events were peripheral sensory neuropathy (29.3%) and hematological toxicity. The results of this analysis support the previously reported brentuximab vedotin efficacy with manageable toxicity. Because of the short-term responses in most patients, a high-dose therapy with stem cell transplantation for responders should be considered as quickly as possible.

Protocol of the "As du Coeur" study: a randomized controlled trial on physical activity maintenance in cardiovascular patients.

BACKGROUND: Although the benefits of supervised physical activity programs in cardiac rehabilitation have been well documented, the amount of physical activity often drops quickly after the end of the supervised period. This trial (registered as ISRCTN77313697 ) will evaluate the effectiveness of an experimental intervention based on habit formation theory applied to physical activity maintenance. METHODS/DESIGN: Cardiovascular patients (N = 56) will be individually randomized into two groups. Two supervised physical activity (SPA) sessions per week will be offered to the first group for 20 weeks. Progressively autonomous physical activity (PAPA) will be offered to the second group as follows: 10 weeks of the same supervised program as the SPA group followed by 10 more weeks in which one supervised session will be replaced by a strategy to build and sustain the habit of autonomous practice of physical activity. The primary outcome is the amount of physical activity measured by the International Physical Activity Questionnaire (IPAQ; Craig et al., Med Sci Sport Exercises 35(8):1381-95, 2003). To compensate for the limited capacity to recruit subjects, multiple IPAQ measurements will be made (at T0, T5, T7, T9 and T12 months after the start of the intervention) and analyzed using the mixed model approach. We will also assess changes in physical and physiological indicators, automaticity of the physical activity behavior, motivation and quality of life. Last, we will assess the cost-effectiveness for each type of program. DISCUSSION: If proven to be effective, the PAPA intervention, which requires fewer supervised sessions, should provide a cost-effective solution to the problem of physical activity maintenance in cardiac rehabilitation.

Clinical and genomic analysis of a randomised phase II study evaluating anastrozole and fulvestrant in postmenopausal patients treated for large operable or locally advanced hormone-receptor-positive breast cancer.

BACKGROUND: The aim of this study was to assess the efficacy of neoadjuvant anastrozole and fulvestrant treatment of large operable or locally advanced hormone-receptor-positive breast cancer not eligible for initial breast-conserving surgery, and to identify genomic changes occurring after treatment. METHODS: One hundred and twenty post-menopausal patients were randomised to receive 1 mg anastrozole (61 patients) or 500 mg fulvestrant (59 patients) for 6 months. Genomic DNA copy number profiles were generated for a subgroup of 20 patients before and after treatment. RESULTS: A total of 108 patients were evaluable for efficacy and 118 for toxicity. The objective response rate determined by clinical palpation was 58.9% (95% CI=45.0-71.9) in the anastrozole arm and 53.8% (95% CI=39.5-67.8) in the fulvestrant arm. The breast-conserving surgery rate was 58.9% (95% CI=45.0-71.9) in the anastrozole arm and 50.0% (95% CI=35.8-64.2) in the fulvestrant arm. Pathological responses >50% occurred in 24 patients (42.9%) in the anastrozole arm and 13 (25.0%) in the fulvestrant arm. The Ki-67 score fell after treatment but there was no significant difference between the reduction in the two arms (anastrozole 16.7% (95% CI=13.3-21.0) before, 3.2% (95% CI=1.9-5.5) after, n=43; fulvestrant 17.1% (95%CI=13.1-22.5) before, 3.2% (95% CI=1.8-5.7) after, n=38) or between the reduction in Ki-67 in clinical responders and non-responders. Genomic analysis appeared to show a reduction of clonal diversity following treatment with selection of some clones with simpler copy number profiles. CONCLUSIONS: Both anastrozole and fulvestrant were effective and well-tolerated, enabling breast-conserving surgery in over 50% of patients. Clonal changes consistent with clonal selection by the treatment were seen in a subgroup of patients.

PET/CT assessment in follicular lymphoma using standardized criteria: central review in the PRIMA study.

PURPOSE: We aimed to compare the standardized central review of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scans performed after induction therapy for follicular lymphoma (FL) in the PRIMA study (Salles et al., Lancet 377:42-51, 2011; Trotman et al., J Clin Oncol 29:3194-3200, 2011) to scan review at local centres. METHODS: PET/CT scans were independently evaluated by two nuclear medicine physicians using the 2007 International Harmonization Project (IHP) criteria (Cheson et al., J Clin Oncol 25:579-586, 2007; Juweid et al., J Clin Oncol 25:571-578, 2007; Shankar et al., J Nucl Med 47:1059-1066, 2006) and Deauville 5-point scale (5PS) criteria (Meignan et al., Leuk Lymphoma 50:1257-1260, 2009; Meignan et al., Leuk Lymphoma 51:2171-2180, 2010; Barrington et al., Eur J Nucl Med Mol Imaging 37:1824-1833, 2010). PET/CT status was compared with prospectively recorded patient outcomes. RESULTS: Central evaluation was performed on 119 scans. At diagnosis, 58 of 59 were recorded as positive, with a mean maximum standardized uptake value (SUVmax) of 11.7 (range 4.6-35.6). There was no significant association between baseline SUVmax and progression-free survival (PFS). Sixty post-induction scans were interpreted using both the IHP criteria and 5PS. Post-induction PET-positive status failed to predict progression when applying the IHP criteria [p = 0.14; hazard ratio (HR) 1.9; 95 % confidence interval (CI) 0.8-4.6] or 5PS with a cut-off ≥3 (p = 0.12; HR 2.0; 95% CI 0.8-4.7). However, when applying the 5PS with a cut-off ≥4, there was a significantly inferior 42-month PFS in PET-positive patients of 25.0% (95% CI 3.7-55.8%) versus 61.4% (95% CI 45.4-74.1%) in PET-negative patients (p = 0.01; HR 3.1; 95% CI 1.2-7.8). The positive predictive value (PPV) of post-induction PET with this liver cut-off was 75%. The 42-month PFS for patients remaining PET-positive by local assessment was 31.1% (95% CI 10.2-55.0%) vs 64.6% (95% CI 47.0-77.6%) for PET-negative patients (p = 0.002; HR 3.3; 95% CI 1.5-7.4), with a PPV of 66.7%. CONCLUSION: We confirm that FDG PET/CT status when applying the 5PS with a cut-off ≥4 is strongly predictive of outcome after first-line immunochemotherapy for FL. Further efforts to refine the criteria for assessing minimal residual FDG uptake in FL should provide a reproducible platform for response assessment in future prospective studies of a PET-adapted approach.

Plasma lipoprotein(a) concentration predicts future coronary and cardiovascular events in patients with stable coronary heart disease.

OBJECTIVE: Association between lipoprotein(a) (Lp(a)) level and a first-ever coronary (CHD) event is recognized. Less is evident in patients with overt CHD and stable symptoms in whom we investigated associations between Lp(a) and future events. APPROACH AND RESULTS: Relationships between Lp(a) concentration and CHD and cardiovascular disease outcomes during 6 years' median follow-up were evaluated in the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study. Lp(a) concentrations were measured in plasma from 7863 patients who had sustained a previous coronary event and been randomized to pravastatin or placebo. Lp(a) levels were categorized by lowest half, third quartile, 75th to 90th percentile, and highest decile. The prognostic value of Lp(a) on outcomes was assessed by fitting a Cox proportional-hazards model after adjustment for other risk factors and baseline cardiovascular disorders. The prognostic value of a change in Lp(a) at year 1 categorized by quartiles was assessed using Cox regression in a landmark model incorporating the above factors and baseline levels. Baseline Lp(a) concentration was associated with total CHD events (P<0.001), total cardiovascular disease events (P=0.002), and coronary events (P=0.03). Greatest risk occurred at >73 mg/dL, upper decile. For events after year 1, an increase in Lp(a) at 1 year was associated with adverse outcomes for total CHD events and total cardiovascular disease events (P=0.002 each). CONCLUSIONS: In the LIPID study, baseline Lp(a) was associated with future cardiovascular disease and CHD events. Increased Lp(a) concentrations after 1 year were also associated with future events, supporting measurement of Lp(a) for risk assessment of patients with known CHD.

Magnitude and Temporal Variations of Socioeconomic Inequalities in the Quality of Life After Early Breast Cancer: Results From the Multicentric French CANTO Cohort.

PURPOSE: Socioeconomic status (SES) influences the survival outcomes of patients with early breast cancer (EBC). However, limited research investigates social inequalities in their quality of life (QoL). This study examines the socioeconomic inequalities in QoL after an EBC diagnosis and their time trends. PATIENTS AND METHODS: We used data from the French prospective multicentric CANTO cohort (ClinicalTrials.gov identifier: NCT01993498), including women with EBC enrolled between 2012 and 2018. QoL was assessed using the European Organisation for Research and Treatment of Cancer QoL Core 30 questionnaire (QLQ-C30). summary score at diagnosis and 1 and 2 years postdiagnosis. We considered three indicators of SES separately: self-reported financial difficulties, household income, and educational level. We first analyzed the trajectories of the QLQ-C30 summary score by SES group. Then, social inequalities in QLQ-C30 summary score and their time trends were quantified using the regression-based slope index of inequality (SII), representing the absolute change in the outcome along socioeconomic gradient extremes. The analyses were adjusted for age at diagnosis, Charlson Comorbidity Index, disease stage, and type of local and systemic treatment. RESULTS: Among the 5,915 included patients with data on QoL at diagnosis and at the 2-year follow-up, social inequalities in QLQ-C30 summary score at baseline were statistically significant for all SES indicators (SIIfinancial difficulties = -7.6 [-8.9; -6.2], SIIincome = -4.0 [-5.2; -2.8]), SIIeducation = -1.9 [-3.1; -0.7]). These inequalities significantly increased (interaction P < .05) in year 1 and year 2 postdiagnosis, irrespective of prediagnosis health, tumor characteristics, and treatment. Similar results were observed in subgroups defined by menopausal status and type of adjuvant systemic treatment. CONCLUSION: The magnitude of preexisting inequalities in QoL increased over time after EBC diagnosis, emphasizing the importance of considering social determinants of health during comprehensive cancer care planning.

Metabolomic prediction of breast cancer treatment induced neurological and metabolic toxicities.

BACKGROUND: Long-term treatment-related toxicities, such as neurological and metabolic toxicities, are major issues in breast cancer. We investigated the interest of metabolomic profiling to predict toxicities. METHODS: Untargeted high-resolution metabolomic profiles of 992 patients with ER+/HER2- breast cancer from the prospective CANTO cohort were acquired (n=1935 metabolites). A residual-based modeling strategy with a discovery and validation cohort was used to benchmark machine learning algorithms, taking into account confounding variables. RESULTS: Adaptive LASSO has a good predictive performance, has limited optimism bias, and allows the selection of metabolites of interest for future translational research. The addition of low-frequency metabolites and non-annotated metabolites increases the predictive power. Metabolomics adds extra performance to clinical variables to predict various neurological and metabolic toxicity profiles. CONCLUSIONS: Untargeted high-resolution metabolomics allows better toxicity prediction by considering environmental exposure, metabolites linked to microbiota, and low-frequency metabolites.

Head impact kinematics and injury risks during E-scooter collisions against a curb.

E-scooters as a mode of transportation is rapidly growing in popularity. This study evaluates head impact conditions and injury risk associated with E-scooter crashes. A multibody model of E-scooter falls induced by wheel-curb collision was built and compared with an experimental E-scooter crash test. A total of 162 crash scenarios were simulated to assess the effect of fall conditions (E-scooter initial speed and inclination, obstacle orientation, and user size) on the head impact kinematics. The forehead hit the ground first in 44% of simulations. The average tangential and normal impact speeds were 3.5 m/s and 4.8 m/s respectively. Nearly 100% of simulations identified a risk of concussion (linear acceleration peak >82 g and rotational acceleration peak >6383 rad/s2) and 90% of simulations suggested a risk of severe head injuries (HIC>700). This work provides preliminary data useful for the assessment and design of protective gears.

Post-Marketing Safety Surveillance of Quadrivalent Influenza Vaccine (VaxigripTetra) in Children Aged 6 to 35 Months in South Korea.

INTRODUCTION: The quadrivalent inactivated split-virion influenza vaccine (QIV; VaxigripTetra®) was initially licensed in South Korea in 2017 for immunization against seasonal influenza in those aged ≥ 3 years, with the indicated age subsequently lowered to include those aged ≥ 6 months in 2018. Here, to comply with South Korean licensure requirements, we undertook a post-marketing surveillance study to assess the safety of QIV in children aged 6-35 months (i.e., extension of the previous age indication to include these young children) in routine clinical practice. METHODS: A multicenter, observational, active safety surveillance of children aged 6-35 months who received a single dose of QIV during a routine healthcare visit was undertaken in South Korea from 15 June 2018 to 14 June 2022. Solicited adverse events (AEs) and unsolicited non-serious AEs were recorded in diary cards, with serious adverse events (SAEs) notified to study investigators. RESULTS: This safety analysis included 676 participants. No AEs led to study termination, and no SAEs were reported. The most frequent solicited injection site reaction was pain in both the ≤ 23-month (12.2% [55/450]) and ≥ 24-month (15.5% [35/226]) age groups. The most frequent solicited systemic reactions were pyrexia and somnolence in the ≤ 23-month age group (6.0% [27/450] each), and malaise (10.6% [24/226]) in the ≥ 24-month age group. Overall, 208 (30.8%) participants experienced 339 unsolicited non-serious AEs, with nasopharyngitis the most common (14.1% [95/676]), and nearly all events (98.8% [335/339]) were considered unrelated to QIV. Grade 3 solicited reactions and unsolicited non-serious AEs were reported in five (0.7%) and three (0.4%) participants, respectively, all of whom recovered by day 7 after vaccination. CONCLUSION: This active safety surveillance study confirms that QIV is well tolerated in children aged 6-35 months in routine clinical practice in South Korea. There were no safety concerns observed in these young children.

Change in the value of work after breast cancer: evidence from a prospective cohort.

BACKGROUND: Return to work (RTW) after cancer can be modulated by psychosocial factors, including a reordering of one's life values, with more emphasis on private life than work-life. This change in patients' outlook on work-life is however poorly understood. METHODS: We used data from a French cohort (CANTO, NCT01993498) of women diagnosed with stage I-III primary breast cancer (BC) prospectively assessing life priorities between work and private life at diagnosis and 2 years after diagnosis. We identified women who reported a shift in life values toward private life, and we investigated the clinical, demographic, work-related, and psychosocial determinants of this change using logistic regressions. RESULTS: Overall, 46% (N = 1097) of the women had reordered their life priorities toward private life 2 years after diagnosis. The factors positively associated with this shift included being diagnosed with stage III BC, perceiving one's job as not very interesting, being an employee/clerk (vs. executive occupation), perceiving no support from the supervisor at baseline, perceiving negative interferences of cancer in daily life, and perceiving a positive impact from experiencing cancer. Depressive symptoms were negatively associated with this shift. CONCLUSION: After BC, there seems to be an important reordering of life values, with more emphasis on private life. This change is influenced by clinical determinants, but also by work-related and psychosocial factors. IMPLICATIONS FOR CANCER SURVIVORS: Stakeholders should consider this change in a patient's outlook on work-life as much as the classical physical late effects when designing post-BC programs to support RTW.

Adjuvant endocrine therapy uptake, toxicity, quality of life, and prediction of early discontinuation.

BACKGROUND: Many patients receiving adjuvant endocrine therapy (ET) for breast cancer experience side effects and reduced quality of life (QoL) and discontinue ET. We sought to describe these issues and develop a prediction model of early discontinuation of ET. METHODS: Among patients with hormone receptor-positive and HER2-negative stage I-III breast cancer of the Cancer Toxicities cohort (NCT01993498) who were prescribed adjuvant ET between 2012 and 2017, upon stratification by menopausal status, we evaluated adjuvant ET patterns including treatment change and patient-reported discontinuation and ET-associated toxicities and impact on QoL. Independent variables included clinical and demographic features, toxicities, and patient-reported outcomes. A machine-learning model to predict time to early discontinuation was trained and evaluated on a held-out validation set. RESULTS: Patient-reported discontinuation rate of the first prescribed ET at 4 years was 30% and 35% in 4122 postmenopausal and 2087 premenopausal patients, respectively. Switching to a new ET was associated with higher symptom burden, poorer QoL, and higher discontinuation rate. Early discontinuation rate of adjuvant ET before treatment completion was 13% in postmenopausal and 15% in premenopausal patients. The early discontinuation model obtained a C index of 0.62 in the held-out validation set. Many aspects of QoL, most importantly fatigue and insomnia (European Organization for Research and Treatment of Cancer QoL questionnaire 30), were associated with early discontinuation. CONCLUSION: Tolerability and adherence to ET remains a challenge for patients who switch to a second ET. An early discontinuation model using patient-reported outcomes identifies patients likely to discontinue their adjuvant ET. Improved management of toxicities and novel more tolerable adjuvant ETs are needed for maintaining patients on treatment.

Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single-arm, phase 2 trial.

BACKGROUND: Diffuse large B-cell lymphoma is a common cancer in elderly patients. Although treatment has been standardised in younger patients, no prospective study has been done in patients over 80 years old. We aimed to investigate the efficacy and safety of a decreased dose of CHOP (doxorubicin, cyclophosphamide, vincristine, and prednisone) chemotherapy with a conventional dose of rituximab in elderly patients with diffuse large B-cell lymphoma. METHODS: We did a prospective, multicentre, single-arm, phase 2 study of patients aged over 80 years who had diffuse large B-cell lymphoma. Patients were included from 38 centres in France and Belgium. All patients received six cycles of rituximab combined with low-dose CHOP (R-miniCHOP) at 3-week intervals. Patients received 375 mg/m(2) rituximab, 400 mg/m(2) cyclophosphamide, 25 mg/m(2) doxorubicin, and 1 mg vincristine on day 1 of each cycle, and 40 mg/m(2) prednisone on days 1-5. The primary endpoint was overall survival, both unadjusted and adjusted for treatment and baseline prognostic factors. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, NCT01087424. FINDINGS: 150 patients were enrolled between Jan 9, 2006, and Jan 23, 2009 and 149 were included in the intention-to-treat analyses. Median age was 83 years (range 80-95). After a median follow-up of 20 months (range 0-45), the median overall survival was 29 months (95% CI 21 to upper limit not reached); 2-year overall survival was 59% (49-67%). In multivariate analyses, overall survival was only affected by a serum albumin concentration of 35 g/L or less (hazard ratio 3·2, 95% CI 1·4-7·1; p=0·0053). Median progression-free survival was 21 months (95% CI 13 to upper limit not reached), with a 2-year progression free survival of 47% (38-56). 58 deaths were reported, 33 of which were secondary to lymphoma progression. 12 deaths were attributed to toxicity of the treatment. The most frequent side-effect was haematological toxicity (grade ≥3 neutropenia in 59 patients; febrile neutropenia in 11 patients). INTERPRETATION: R-miniCHOP offers a good compromise between efficacy and safety in patients aged over 80 years old. R-miniCHOP should be considered as the new standard treatment in this subgroup of patients. FUNDING: Groupe d'Etude des Lymphomes de l'Adulte (GELA).

Post-marketing Surveillance of a Quadrivalent Influenza Vaccine (Vaxigrip Tetra) in South Korea.

INTRODUCTION: In 2017, a quadrivalent inactivated split-virion influenza vaccine (QIV; Vaxigrip Tetra®, Sanofi) was licensed in South Korea for active immunization against influenza A and influenza B viruses in individuals aged 3 years or older, which was subsequently extended to individuals aged 6 months or older in 2018. Post-marketing surveillance trials are mandatory in South Korea to retain drug licensure. Here, we assessed the safety of QIV in routine clinical practice in South Korea. METHODS: This was an open, multicenter, observational, active safety surveillance study conducted between 20 June 2017 and 19 June 2021 at 10 study sites in South Korea in individuals aged 3 years or older who received a single dose of QIV during a routine healthcare visit. The participants or their legally acceptable representatives were instructed to record any adverse reactions (solicited events) and unsolicited non-serious adverse events (AE) in diary cards, and notify study investigators in case of serious adverse events (SAE). RESULTS: Overall, 663 participants were included in this study. There were no AEs leading to study termination, and no SAEs reported. Injection site pain (278 [41.9%]) was the most frequent solicited injection site reaction, with myalgia (250 [37.7%]) and malaise (236 [35.6%]) the most frequent solicited systemic reactions. Grade 3 solicited injection site and systemic reactions were reported by 8 (1.2%) and 13 (2.0%) participants, respectively; most participants with solicited reactions recovered without the need for further action. Overall, 39 (5.9%) participants experienced 49 unsolicited non-serious AEs with the most frequently reported being nasopharyngitis (19 [2.9%]). Grade 3 unsolicited non-serious adverse events were reported in 1 (0.2%) participant. None of the unsolicited non-serious AEs were considered to be related to QIV. CONCLUSION: This post-marketing surveillance study confirms that QIV is well tolerated and has an acceptable safety profile in routine practice in South Korea. No unexpected safety concerns were identified. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05406180.

Neoadjuvant chemotherapy and radiotherapy for locally advanced breast cancer: Safety and efficacy of reverse sequence compared to standard technique?

BACKGROUND: The reverse sequence of neoadjuvant chemotherapy, preoperative radiotherapy, mastectomy then immediate breast reconstruction is currently proposed for selected patients with locally advanced breast cancer. Few studies have compared it to the standard sequence of neoadjuvant chemotherapy, mastectomy and radiotherapy with or without differed reconstruction. Our study compares overall (OS) and recurrence-free (RFS) survivals of breast cancer patients treated with reverse sequence compared to the standard technique. METHODS: In this retrospective, single center study at a Comprehensive Cancer Center in France, patients were included if: female, age <65y, had received neoadjuvant chemotherapy, mastectomy and radiotherapy, and were M0. Outcomes for patients treated by reverse sequence (RS) are compared to those for patients treated by standard sequence (ST). Data was collected from medical records. RESULTS: From January 2009 to April 2018, 222 eligible patients were treated, 46 by RS and 176 by ST. Mean follow-up was 61.7 months. Five-year OS and RFS did not differ between groups. 5-yr OS: 88.4% 95%CI [74.1-95.0] for RS and 81.5% 95%CI [74.0-87.0] for ST (P = 0.4412); 5-yr RFS: 78.3% 95%CI [61.9-88.3] for RS and 70.1% 95%CI [62.2-76.7] for ST (P = 0.3003). Overall treatment time was significantly shorter in the RS group, and the rate of severe surgical complications did not differ between groups. CONCLUSIONS: For locally advanced breast cancer patients with an indication for radiation therapy the reverse sequence offers similar safety and efficacy results as the standard treatment while allowing immediate breast reconstruction. However, careful patient selection is necessary, particularly with regard to preoperative lymph node invasion.