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Background: Breast cancer, a potential traumatic stressor, may be accompanied by positive changes, such as post-traumatic growth (PTG), which may allow patients to overcome this stressful event more easily. Our aim was to identify factors associated with PTG in breast cancer survivors (BCSs)., Methods: We conducted a cross-sectional study in Seintinelles volunteers who answered online questionnaires. PTG was measured using the Post-Traumatic Growth Inventory (PTGI). Data on sociodemographic, health-related factors and lifestyle habits, fear of cancer recurrence, health locus of control, coping strategies, and time perspective were collected., Results: The study included 821 BCSs aged 26 to 79 years, one to 16 years after cancer diagnosis. Mean of PTG scores were: relating to others 20.27 ± 6.61; new possibilities 14.00 ± 5.44; personal strength 12.24 ± 4.32; spiritual change 2.95 ± 2.54; appreciation of life 10.59 ± 3.00 and total PTG 60.05 ± 18.11. Several factors were associated with PTG: health-related factors (satisfaction with one's own health, longer time since diagnosis), lifestyle habits (increasing physical activity level and stopping or reducing alcohol consumption after diagnosis), elements of locus of control (powerful others), coping strategies (positive thinking, seeking social support) and time perspective (present hedonistic), which were significantly positively associated with PTG. Chance locus of control and coping avoidance were inversely related to several PTG domains, even several years after diagnosis., Conclusions: PTG may be increased in BCSs by acting on its modifiable factors. This includes adopting healthy behaviours, such as increasing physical activity and stopping/reducing alcohol consumption, and developing locus of control elements, such as powerful others, and coping strategies, such as positive thinking and seeking social support, through targeted interventions. Further studies, especially longitudinal studies, are needed to confirm the observed associations between health behaviours, health locus of control, time perspective, and PTG scores. Other measures, such as post-traumatic stress, should be considered because of possible inferences with PTG., Competing Interests: Declarations. Ethics approval and consent to participate: The project has been approved by the Research Ethics Committee “Comité de Protection des Personnes Nord-Ouest II” on July 12, 2020 (File #20.05.26.59658; EudraCT/ID-RCB: #2020-A01545-34). All methods were performed in accordance with the relevant guidelines and regulations (e.g. Declaration of Helsinki). All Seintinelles volunteers received the necessary information about the study and gave their informed consent to participate online, on the Seintinelles platform. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: MYC-driven lymphomas are a subset of B-cell lymphomas characterized by genetic alterations that dysregulate the expression of the MYC oncogene. When overexpressed, typically through chromosomal translocations, amplifications, or other mechanisms, MYC can drive uncontrolled cell growth and contribute to cancer development. MYC-driven lymphomas are described as aggressive entities which require intensive treatment approaches and can be associated with poor prognosis. In the absence of direct MYC-targeting therapy, epigenetic drugs called BET inhibitors (BETi) were shown to reduce MYC levels by disrupting BRD4-dependent transcription associated with the expression of MYC, as well as other oncogenes. Here, we used BETi as molecular tools to better understand oncogenic dependencies in a panel of cell line models of MYC-driven B-cell lymphoma selected to represent their genetic heterogeneity., Results: We first showed that, in these models, MYC expression level does not strictly correlate to the presence of gene alterations. Our data also demonstrated that BETi induces similar growth arrest in all lymphoma cell lines independently of MYC mutational status or expression level. In contrast, BETi-induced cell death was only observed in two cell lines presenting the highest level of MYC protein. This suggests that some MYC-driven lymphoma could present a stronger dependency on MYC for their survival which cannot be predicted on the sole basis on their genetics. This hypothesis was confirmed by gene invalidation experiments, which showed that MYC loss recapitulates the effect of BETi treatment on both cell proliferation and survival, confirming MYC oncogene dependency in models sensitive to BETi cytotoxicity. In contrast, the growth arrest observed in cell lines resistant to BETi-induced apoptosis is not mediated through MYC, but rather through alternative pro-proliferative or oncogenic pathways. Gene expression profiling revealed the basal activation of a specific non-canonical WNT/Hippo pathway in cell death-resistant cell lines that could be targeted in combination therapy to restore BETi cytotoxicity., Conclusion: This work brings new insights into the complexity of MYC-dependencies and unravels a novel targetable oncogenic pathway in aggressive B-cell lymphomas., Competing Interests: Declarations. Ethics approval and consent to participate: Non-applicable. Consent for publication: Non-applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Assess subsequent cardiovascular events and all-cause mortality in patients with intact abdominal aortic aneurysm (AAA) treated by endovascular aneurysm repair (EVAR) according to the existence of isolated endoleak type 2 (EL 2 ) at 1 year after EVAR implantation., Methods: This retrospective, single-center study included patients treated with EVAR between 2010 and 2017 in the vascular surgery department of the University Hospital of Lyon with an infrarenal AAA > 50 mm. The baseline clinical characteristics collected just before EVAR were retrieved from electronic patient records of our institution. AAA characteristics, procedure, and the 1-year postoperative computed tomography angiography (CTA) were reported. Study end points, major adverse cardiovascular events (MACE), major adverse lower-extremity events (MALE), and all-cause mortality were recorded during follow-up. Patients were divided into 2 groups according to the presence of isolated EL 2 (EL 2 +) or absence (EL 2 -) of any endoleak on CTA at 1 year. MACE, MALE, and all-cause mortality were compared between both groups., Results: During the study period, 589 patients were treated by endovascular surgery and 207 were included. According to the CTA results at 1 year, 60 patients (29%) were included in the EL 2  + group and 147 patients (71%) in the EL 2 - group. A total of 109 patients (53%) experienced a MACE or MALE; significantly fewer patients in the EL 2  + than in the EL 2 - group did so (P = 0.009). There were 47 patients (23%) who experienced at least 1 MALE, and the frequency was significantly lower in the EL 2  + group (P = 0.017)., Conclusions: Patients with AAA treated by EVAR who did not develop EL 2 at 1 year were at higher risk of MALE during follow-up. This might be explained by more frequent symptomatic lower extremity peripheral arterial disease at baseline in this group. These patients therefore require a closer follow-up and strict control of cardiovascular risk factors to prevent cardiovascular morbi-mortality., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Malnutrition and sarcopenia are challenges for patients with metastatic breast cancer and have been proposed as independent prognostic factors. Very few studies have addressed the temporal evolution of these parameters and, notably, the separate and combined analysis of sarcopenia and malnutrition. This study aimed to i) determine the prevalence of malnutrition and sarcopenia, individually and combined, and their evolution over time, ii) identify risk factors for each condition, and iii) explore their impact on overall survival (OS)., Methods: This retrospective study was conducted on 111 patients treated for at least a third-line metastatic breast cancer at the Institut Curie between January 1st and March 31st, 2018. Solitary malnutrition was defined from weight loss and body mass index values while solitary sarcopenia was defined solely based on low muscle mass. We analyzed solitary malnutrition, solitary sarcopenia, and then malnutrition with or without sarcopenia, at three key stages (T1: diagnosis of metastasis, T2: initiation of third-line treatment, and T3: 3-month re-evaluation). Univariate and multivariate logistic regression analyses were conducted to investigate the risk factors. We performed Cox proportional hazards analyses for each variable., Results: At T1, the prevalence of solitary malnutrition, solitary sarcopenia and malnutrition with or without sarcopenia was 18.6%, 36.1% and 48.9% respectively, increasing to 27.7%, 45.5% and 56.6% at T2. At T2, in multivariate logistic regression analyses, patients aged over 60 years were at an elevated risk of experiencing solitary malnutrition as well as malnutrition with or without sarcopenia, but not solitary sarcopenia. In multivariate analyses, solitary malnutrition was significantly associated with poorer OS (HR 2.2 [95% CI 1.1-4.1], p = 0.02), while solitary sarcopenia and malnutrition with or without sarcopenia showed no association., Conclusion: Solitary malnutrition and sarcopenia were highly prevalent in patients with metastatic breast cancer, affecting around a quarter and half of patients respectively at third-line treatment initiation. Notably, solitary malnutrition emerged as a prognostic factor for overall survival, whereas no significant association was observed for solitary sarcopenia or malnutrition with or without sarcopenia. This highlights the critical need for early identification of patients at risk of malnutrition and the importance of timely intervention., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Recent retrospective studies suggest potential large patient's benefit through proper timing of immune checkpoint blockers (ICB). The association between ICB treatment timing and patient survival, neoplastic response and toxicities was investigated, together with interactions with performance status (PS) and sex., Methods: A cohort of patients with metastatic or locally advanced solid tumors, who received pembrolizumab, nivolumab, atezolizumab, durvalumab, or avelumab, alone or with concomitant chemotherapy, between November 2015 and March 2021, at the Centre Leon Bérard (France), was retrospectively studied., Results: 361 patients were investigated (80% non-small cell lung cancer patients, mean [SD] age: 63 [11] years, 39% of women, 83% PS0-1 at first infusion, 19% received concomitant chemotherapy). ICB were administered from 07:25 to 17:21 and optimal morning/afternoon cut-off was 11:37. Morning infusions were associated with increased OS as compared to afternoon (median 30.3 vs 15.9 months, p = 0.0024; HR 1.56 [1.17-2.1], p = 0.003). A strong PS-timing interaction was found (PS0-1 patients, HR=1.53 [1.10-2.12], p = 0.011; PS2-3 patients, HR=0.50 [0.25-0.97], p = 0.042). Morning PS0-1 patients displayed increased OS (median 36.7 vs 21.3 months, p = 0.023), partial/complete response rate (58% vs 41%, p = 0.027), and grade1-3 toxicities (49% vs 34%, p = 0.028). Mortality risk ratio between infusions at worst time-of-day, estimated at 13:36 [12:48-14:23], and in early morning was equal to 4.8 ([2.3-10.1], p = 0.008). Timing differences in toxicities resulted significant only in female patients (women vs men: p < 0.001 vs 0.4)., Conclusions: Early morning ICB infusion was associated with increased OS, response, and toxicities in patients with PS0-1 as compared to later infusions within the day. Prospective randomized trials are needed to confirm this retrospective study., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Pierre Heudel reported grants from AstraZeneca and personal fees from LILLY, ASTRAZENECA, PFIZER, NOVARTIS, SEAGEN, PIERRE FABRE, MSD, GILEAD outside the submitted work. Hugo Crochet reported grants from Daichi, Nutricia and Freisenius. The other authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Acting on modifiable risk factors can prevent approximately 40% of cancers. Knowing the factors that lead people to adopt healthy behaviors is crucial for designing effective primary prevention campaigns. Our study attempts to provide knowledge in this direction., Methods: This cross-sectional study was conducted via the Seintinelles collaborative research platform in a community of women without a personal cancer history, and volunteering to take online questionnaires. We collected data on sociodemographic and health factors, knowledge of cancer risk factors, behaviors, and possible behavior changes (tobacco/alcohol use, diet, body weight, and physical activity) in the last 10 years., Results: The study involved 1465 women aged between 18 and 84 years. Factors such as young age, living alone, and obesity were associated with some positive or negative behavior changes. Being professionally active and having comorbidities favored certain positive behavior changes, while having dependent children, living in a rural area, and being hospitalized were associated with negative or no change in behaviors. Lack of knowledge about modifiable risk factors for cancer was associated with the non-adoption of various healthy behaviors (consumptions of fruit and vegetables, processed and red meat; physical activity). Only 5.5% of participants currently reported to be compliant with seven public health recommendations (smoking; alcohol, fruit/vegetables, and red/processed meat intakes; body mass index; and physical activity)., Conclusions: This study allowed to identify the need to increase the level of knowledge on modifiable risk factors for cancer among the general population and to better clarify the content of prevention messages., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: The importance of body composition and sarcopenia is well-recognized in cancer patient outcomes and treatment tolerance, yet routine evaluations are rare due to their time-intensive nature. While CT scans provide accurate measurements, they depend on manual processes. We developed and validated a deep learning algorithm to automatically select and segment abdominal muscles [SM], visceral fat [VAT], and subcutaneous fat [SAT] on CT scans., Materials and Methods: A total of 352 CT scans were collected from two cancer centers. The detection of the third lumbar vertebra and three different body tissues (SM, VAT, and SAT) were annotated manually. The 5-fold cross-validation method was used to develop the algorithm and validate its performance on the training cohort. The results were validated on an external, independent group of CT scans., Results: The algorithm for automatic L3 slice selection had a mean absolute error of 4 mm for the internal validation dataset and 5.5 mm for the external validation dataset. The median DICE similarity coefficient for body composition was 0.94 for SM, 0.93 for VAT, and 0.86 for SAT in the internal validation dataset, whereas it was 0.93 for SM, 0.93 for VAT, and 0.85 for SAT in the external validation dataset. There were high correlation scores with sarcopenia metrics in both internal and external validation datasets., Conclusions: Our deep learning algorithm facilitates routine research use and could be integrated into electronic patient records, enhancing care through better monitoring and the incorporation of targeted supportive measures like exercise and nutrition., Competing Interests: Authors DB and VR were employed by QuantaCell. Author DB was employed by IMAG. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Delrieu, Blanc, Bouhamama, Reyal, Pilleul, Racine, Hamy, Crochet, Marchal and Heudel.)

Background: Health-Related Quality of life (HRQoL) in cancer survivors can be significantly affected in the long-term by various consequences resulting from differing levels of severity of cancer and its treatments. Our objective was to identify factors associated with HRQoL in breast cancer survivors (BCSs) and cancer-free women (CFWs)., Methods: We conducted a cross-sectional study in Seintinelles volunteers who answered online questionnaires between September 15, 2020 and February 5, 2021. HRQoL was measured using the World Health Organization Quality of Life-BREF questionnaire. We collected data on sociodemographic and health-related factors, lifestyle habits, coping mechanisms, locus of control, and health literacy. SAS version 9.4 statistical software was used for analyses. We performed descriptive analyses of the characteristics of the participants in each group and compared these characteristics between the two groups using the Chi 2 test or the Student t-test. The adjusted means of the scores of different psychometric scales were calculated and compared using the method of least squares to fit general linear models (GLM) while adjusting for various factors. Multiple linear or multiple logistic regression models were used to assess the factors associated with WHOQOL-BREF scores, separately, in the two groups of participants., Results: The study involved 722 BCSs and 1359 CFWs aged 26-75 years. BCSs had significantly lower physical health scores and were less likely to be satisfied with their health compared to CFWs (59.5 vs. 63.2, p < 0.0001; and 56.5% vs. 75.2%, p = 0.002, respectively). In both groups, some common factors were positively associated with physical health (high financial level, being professionally active, normal BMI, good health status, alcohol consumption, higher values (> 22) of internal locus of control); or inversely associated (neurological and sleep problems, over two medical consultations/year). In BCSs, treatment by mastectomy or radiation therapy/brachytherapy, a short-time since diagnosis, current cancer therapy, and presence of sequalae were inversely associated with physical health. BCSs' health satisfaction was diminished with lower values of coping by positive thinking (≤ 14) and seeking social support (≤ 18)., Conclusions: HRQoL can be improved by developing strategies that increase internal locus of control and coping (positive thinking, problem-solving and seeking social support), and through health literacy., (© 2023. The Author(s).)

Introduction: The number of cancer survivors increases and their risks of recurrence, second cancer, morbidity and death is high; measures to prevent these risks are thus critical. Knowing the factors that lead cancer survivor to adopt or not healthy behaviours is crucial for designing effective prevention campaigns and better support them in after-cancer. Our study attempts to provide additional knowledge in this direction., Methods: This retrospective study was conducted via the Seintinelles collaborative research platform in a community of women with cancer volunteering to take online questionnaires. We collected data on sociodemographic factors and health, knowledge of cancer risk factors, and possible behaviour changes (tobacco/alcohol use, diet, physical activity) after cancer diagnosis., Results: The study involved 1180 women aged between 26 and 79 years. Several cancer-related factors (cancer other than breast cancer, longer time since diagnosis, taking drug treatment for cancer, sequelae, negative evolution of the cancer) favoured certain positive changes in behaviour. Sociodemographic factors (age, habitat environment, currently employed, living status, dependent children) or factors related to health (general condition, presence of comorbidities, neurological problems, hospitalizations, body mass index) favoured or not certain changes in behaviour. Lack of knowledge about modifiable risk factors for cancer was associated with not adopting healthy behaviours after cancer., Discussion: This study made it possible to identify important elements to be addressed in order to improve cancer risk prevention messages., (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Malnutrition is associated with a greater risk of morbidity and mortality and lower tolerance to chemotherapy. Our purpose was to study the association between nutritional status and the efficiency and tolerance of immunotherapy in non-small cell lung cancer (NSCLC). Nutritional and oncological data were reported at 2 months (M2) and 4 months (M4) after the initiation of immunotherapy (M0). The influence of nutritional status at M0 was estimated with the efficacy and toxicity of immunotherapy at M2 to M4. In total, 127 patients were included in the study, and nutritional status was estimated at M0 for 120 patients: 67% were not malnourished, 20% presented with moderate malnutrition, and 13% presented with severe malnutrition. There was no significant link between the nutritional status at M0 and the toxicity of immunotherapy at M2 and M4. However, severe malnutrition was significantly associated with treatment efficacy at M2 ( p = 0.04) and with a lower survival rate with an HR (Hazard Ratio) = 2.32-95% C.I: 1.13-4.75 ( p = 0.02). Furthermore, a monthly decrease of 1% of the weight had an HR = 1.17-95% C.I: 1.13-1.21 ( p = 0.0001). Severe malnutrition and weight loss are independent factors associated with lower survival. Studies integrating the systemic detection of sarcopenia with a closer nutritional follow-up could highlight an improvement in survival.

Purpose: To evaluate the dynamics of the determinants of returning to work (RTW) in a population of patients treated for breast cancer (BC) in a real-world setting., Method: We conducted a retrospective study including 1278 BC patients working or looking for work at the time of diagnosis. We performed a focused principal component analysis to highlight the dimensions of a persistent decline in work capacity. Logistic regression analyses were performed to identify correlates of non-RTW 1 and 2 years after treatment., Results: One-third (31%, n = 389) of patients continued working during treatment. At study inclusion, 1100 patients had returned to work (89%). Three-quarters (n = 508, 75%) of the women reported a decline in work capacity 1 year after RTW and 22% (n = 148) presented a persistent decline in work capacity 2 years after the diagnosis. The odds ratio for non-RTW at 1 year was significantly higher for patients treated with a combination of chemotherapy and trastuzumab (OR = 1.72, 95% CI [1.07-2.76]), manual workers (OR = 3.99, 95% CI [1.54-10.81]), patients with lower incomes (OR = 2.33, 95% CI [1.29-4.19]), and patients experiencing fatigue (OR = 1.81, 95% CI [1.34-2.48]). The odds ratio for non-RTW at 2 years was higher for various occupational categories (OR = 3.49, 95% CI [1.89-6.74] for clerks, OR = 4.58, 95% CI [1.48-12.82] for self-employed workers, OR = 8.98, 95% CI [2.69-27.89] for manual workers), patients with comorbidities (OR = 2.80, 95% CI [1.61-4.93]), and patients experiencing anxiety symptoms (OR = 2.54, 95% CI [1.18-5.76]), while the impact of the type of treatment was no longer significantly associated with RTW., Conclusion: The determinants of RTW change over time. Patients should be offered supportive interventions tailored to risk factors and time from diagnosis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Research Question: What are the real-life oncofertility practices in young women diagnosed with breast cancer?, Design: The FEERIC (FErtility, prEgnancy, contRaceptIon after breast Cancer in France) study is a web-based cohort study launched with the French collaborative research platform Seintinelles. The current work is based on the enrolment self-administered questionnaire of 517 patients with prior breast cancer diagnosis, free from relapse and aged 18 to 43 years at inclusion (from 12 March 2018 to 27 June 2019)., Results: Median age at breast cancer diagnosis was 33.6 years and 424 patients (82.0%) received chemotherapy. Overall, 236 (45.6%) patients were offered specialized oncofertility counselling, 181 patients underwent at least one fertility preservation procedure (FPP); 125 (24.2%) underwent one or more FPP with material preservation (oocytes n = 108, 20.9%; embryos n = 31, 6.0%; ovarian cryopreservation n = 6, 1.2%) and 78 patients received gonadotrophin-releasing hormone agonists (15.1%). With a median follow-up of 26.9 months after the end of treatments, 133 pregnancies had occurred in 85 patients (16.4%), including 20 unplanned pregnancies (15.0%). Most of the pregnancies were natural conceptions (n = 113, 87.6%), while 16 (12.4%) required medical interventions. For the planned pregnancies, median time to the occurrence of an ongoing pregnancy was 3 months. Patients who had an unplanned pregnancy reported lower rates of information on the consequences of the treatments on fertility (P = 0.036) at diagnosis., Conclusions: Most of the patients were not offered proper specialized oncofertility counselling at the time of breast cancer diagnosis. Naturally conceived pregnancies after breast cancer were much more frequent than pregnancies resulting from the use of cryopreserved gametes. Adequate contraceptive counselling seems as important as information about fertility and might prevent unplanned pregnancies., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Breast cancer (BC) has particular characteristics in young women, with diagnosis at more advanced stages, a poorer prognosis and highly aggressive tumors. In NeoFit, we will use an activity tracker to identify and describe various digital profiles (heart rate, physical activity, and sleep patterns) in women below the age of 45 years on neoadjuvant chemotherapy for BC., Methods: NeoFit is a prospective, national, multicenter, single-arm open-label study. It will include 300 women below the age of 45 years treated with neoadjuvant chemotherapy for BC. Participants will be asked to wear a Withing Steel HR activity tracker round the clock for 12 months. The principal assessments will be performed at baseline, at the end of neoadjuvant chemotherapy and at 12 months. We will evaluate clinical parameters, such as toxicity and the efficacy of chemotherapy, together with quality of life, fatigue, and parameters relating to lifestyle and physical activity. The women will complete REDCap form questionnaires via a secure internet link., Discussion: In this study, the use of an activity tracker will enable us to visualize changes in the lifestyle of young women on neoadjuvant chemotherapy for BC, over the course of a one-year period. This exploratory study will provide crucial insight into the digital phenotypes of young BC patients on neoadjuvant chemotherapy and the relationship between these phenotypes and the toxicity and efficacy of treatment. This trial will pave the way for interventional studies involving sleep and physical activity interventions., Trial Registration: Clinicaltrials.gov identifier: NCT05011721 . Registration date: 18/08/2021., (© 2022. The Author(s).)

Introduction: Patients with metastatic non-small cell lung cancer (mNSCLC) suffer from numerous symptoms linked to disease and treatment which may further impair the patient's overall condition. In addition to its benefits on quality of life and fatigue, physical exercise may improve treatment response, notably due to its known effects on the immune system. The ERICA study is designed to assess the feasibility of a supervised acute physical exercise therapy realised immediately prior immune-chemotherapy infusion in patients with mNSCLC. Secondary objectives will examine the effects of acute exercise combined with an unsupervised home-walking programme on clinical, physical, psychosocial and biological parameters., Methods and Analysis: ERICA is a prospective, monocentric, randomised controlled, open-label feasibility study conducted at the Centre Léon Bérard Comprehensive Cancer Center (France). Thirty patients newly diagnosed with mNSCLC will be randomised (2:1 ratio) to the 'exercise' or the 'control' group. At baseline and during the last treatment cycle, participants in both groups will receive Physical Activity recommendations, and two nutritional assessments. In the exercise group, participants will receive a 3-month programme consisting of a supervised acute physical exercise session prior to immune-chemotherapy infusion, and an unsupervised home-based walking programme with an activity tracker. The acute exercise consists of 35 min interval training at submaximal intensity scheduled to terminate 15 min prior to infusion. Clinical, physical, biological and psychosocial parameters will be assessed at baseline, 3 and 6 months after inclusion. Biological measures will include immune, inflammatory, metabolic, oxidative stress biomarkers and molecular profiling., Ethics and Dissemination: The study protocol was approved by the French ethics committee (Comité de protection des personnes Ile de France II, N°ID-RCB 20.09.04.65226, 8 December 2020). The study is registered on ClinicalTrials.gov (NCT number:NCT04676009) and is at the pre-results stage. All participants will sign an informed consent form. The findings will be disseminated in peer-reviewed journals and academic conferences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: In Europe, 20,000 Adolescent and Young Adults (AYAs) aged 15-25 years are diagnosed with cancer annually. Although prognosis is good, AYA cancer survivors are at greater risk of second primary cancers, cardiovascular disease, and various long-term effects. Benefits of physical activity (PA) in AYAs reported in current studies remain difficult to generalize; none has been performed in France. This single-arm intervention study tested the feasibility of combining hospital-based supervised and home-based unsupervised physical activity sessions (PAS) and providing cancer prevention recommendations for AYAs. Methods: The AYAs attended PAS concomitant to treatment and participated in one face-to-face prevention interview. PA (international physical activity questionnaire), 6-min walk distance (6MWD), sedentarity, anthropometrics, quality of life (QoL), and fatigue were assessed at baseline (T1) and end of intervention (T2). PA, satisfaction and cancer prevention behaviors were assessed 1 year after baseline (T3). Results: Fifty-nine AYAs (mean 19 years) participated in the study. Acceptability and attrition were 80% and 12%, respectively. Between T1 and T2, 6MWD and global QoL improved ( p  < 0.001), and fatigue decreased ( p  = 0.003). Total PA improved and sitting time decreased ( p  < 0.001) overall (T1-T3). Assessment at T3 showed interindividual differences in how participants considered risk factors (e.g., more attention to PA, UV exposures, nutrition). Conclusion: Combined supervised and unsupervised home-based PAS in AYAs undergoing cancer treatment is acceptable and feasible. The program contributes to maintaining and improving physical fitness and QoL, while reducing fatigue and other cancer and treatment symptoms. Larger randomized controlled trials are needed to confirm these results.

Background: Carotid atherosclerotic plaques remain silent until their rupture, which may lead to detrimental ischemic events such as strokes. This is due, in part, to intraplaque hemorrhages (IPH) and the resulting inflammatory processes, which may promote carotid plaque vulnerability. Currently, the benefits of carotid endarterectomy remain unclear for asymptomatic patients. Interestingly, the completion of physical activity (PA) may have beneficial effects; however, the paucity of current data warrants robust longitudinal interventions. We therefore aim to study the effects of a 6-month longitudinal personalized home-based PA program on IPH, biological, and inflammatory markers in asymptomatic stroke patients., Methods: Eighty patients (≥ 18 years old) will be recruited for the Physical Activity and Carotid Atherosclerotic Plaque Hemorrhage (PACAPh) clinical trial from the Hospices Civils de Lyon. Patients will be eligible if they present with carotid stenosis ≥ 50% and are asymptomatic from any ischemic events for at least 6 months. Recruited patients will be randomized into either a PA or a control group, and assessed at baseline and after 6 months. At both time points, all patients will be assessed using magnetic resonance imaging to assess IPH, blood sampling to measure inflammatory markers and monocytic phenotyping, PA and sedentary behavior questionnaires, 6-min walking test, and maximal isometric quadricep contraction test. The randomized PA intervention will consist of reaching a daily walking step goal individually tailored to each patient. Steps will be collected using a wirelessly connected wristband. The number of steps completed by individuals in the PA group will be re-evaluated bimonthly to encourage walking habits., Discussion: The PACAPh study is the first of its kind representing a feasible, easily accessible therapeutic strategy for asymptomatic stroke patients. We hypothesize that the personalized home-based PA program will reduce IPH and modulate inflammatory and biological parameters in patients presenting with carotid plaques. If the results of the PACAPh study prove to be beneficial on such health parameters, the implementation of such kind of intervention in the daily treatment of these patients would be an advantageous and cost-effective practice to adopt globally., Trial Registration: This study has been approved by the National Ethics Committee (IDRCB:2019-A01543-54/SI:19.06.21.40640). ClinicalTrials.gov NCT04053166., (© 2022. The Author(s).)

Purpose: Digitalization of the health care system is transforming cancer patient care. Although many studies have investigated the determinants of a limited digital health literacy, the association between frailty factors and overall survival (OS) of these patients has never been assessed., Methods: A retrospective noninterventional study included 15,244 adult patients with cancer diagnosed between January 1, 2015, and December 31, 2017, and treated at the Centre Léon Bérard. Limited e-health literacy was defined as the absence of an e-mail address in the electronic patient record. An Inverse Probability of Treatment-Weighted Kaplan-Meier estimate and a multivariate Cox proportional hazards model including interaction terms were used to adjust for confounding on measured covariates., Results: In total, 15,244 adults with cancer were included: 55% women, with a median age of 62 years (19-103), and 35.5% had a metastatic disease. More than half (n = 8,771, 57.5%) had entered their e-mail address in their electronic patient record, and 4,020 (26.4%) opened their own patient portal. The median follow-up was 3.6 years (range: 0-6.8). Inverse Probability of Treatment-weighted Kaplan-Meier estimates showed a significantly better OS for patients with an e-mail address ( P < .001). In multivariate analysis integrating interaction terms, male gender (hazard ratio [HR] = 1.27; 95% CI, 1.15 to 1.41; P < .001), older age (HR = 1.02; 95% CI, 1.02 to 1.03; P < .001), de novo metastatic setting (HR = 2.63; 95% CI, 2.47 to 2.79; P < .001), and no e-mail address (HR = 1.63; 95% CI, 1.33 to 2.00; P < .001) were significantly associated with worse OS., Conclusion: Our results support a strong association between the limited level of literacy and OS. A more in-depth study integrating variables such as socioeconomic level and location of residence would enrich these results., Competing Interests: Pierre E. HeudelHonoraria: Pfizer, Novartis (Inst), Seattle Genetics, Pierre Fabre, Amgen, AstraZeneca (Inst), Roche, MylanConsulting or Advisory Role: Novartis (Inst), Seattle GeneticsResearch Funding: Fresenius (Inst)Travel, Accommodations, Expenses: Pfizer, Novartis, Roche, Lilly Hugo CrochetResearch Funding: Nutricia (Inst), Fresenius Kabi (Inst) Gisèle ChvetzoffHonoraria: Grunenthal (Inst), Medtronic (Inst)Travel, Accommodations, Expenses: Grunenthal, Keocyt Jean-Yves BlayLeadership: Innate PharmaHonoraria: Roche, AstraZeneca, PharmaMar, MSD, BMS, Bayer, Ignyta, DecipheraConsulting or Advisory Role: Roche, PharmaMar, Deciphera, Blueprint Medicines, Bayer, Karyopharm TherapeuticsResearch Funding: GlaxoSmithKline (Inst), PharmaMar (Inst), Novartis (Inst), Bayer (Inst), Roche (Inst), BMS (Inst), MSD (Inst), Deciphera (Inst), AstraZeneca (Inst), OSE Pharma (Inst)Travel, Accommodations, Expenses: RocheNo other potential conflicts of interest were reported.

Objective: The objective of this study is to assess the physical activity interest and preferences of cancer patients aged over 70 years during oncological treatments and to explore how demographic characteristics may modulate preferences., Methods: From April to May 2018, this cross-sectional study collected data from self-administered questionnaire regarding physical activity interest and preferences in cancer patients receiving oncological treatments in a regional cancer centre., Results: A total of 144 patients completed the questionnaire. Two thirds (n = 95) showed interest in participating in dedicated physical activity programme during oncologic treatments. Patients preferred to exercise in group activities, under the supervision of an exercise instructor, once a week, at a moderate intensity, for 30 min session, in a community fitness centre. Women significantly preferred exercises to improve flexibility (p = 0.03) and to receive counselling in a group (p = 0.03), whereas men preferred to practise strength training (p = 0.02) and to receive counselling with brochures (p = 0.02). As age increases, participants were significantly more inclined to practise physical activity to improve their balance (p = 0.01)., Conclusion: These preliminary results will facilitate the design of programmes considering current physical activity preferences in older adults with cancer, which could ensure better adherence to physical activity programmes and, in turn, improved health outcomes., (© 2021 John Wiley & Sons Ltd.)

Introduction: Despite safety and benefits of physical activity during treatment of localised breast cancer, successful exercise strategies remain to be determined. The primary objective of the 'dispositif connecté', that is, connected device in English trial is to evaluate the efficacy of two 6-month exercise interventions, either single or combined, concomitant to adjuvant treatments, on the physical activity level of patients with breast cancer, compared with usual care: an exercise programme using a connected device (activity tracker, smartphone application, website) and a therapeutic patient education intervention. Secondary objectives are to evaluate adherence to interventions, their impact at 6 and 12 months, representations and acceptability of interventions, and to assess the cost-effectiveness of the interventions using quality-adjusted life-years., Methods and Analysis: This is a 2×2 factorial, multicentre, phase III randomised controlled trial. The study population (with written informed consent) will consist of 432 women diagnosed with primary localised invasive breast carcinoma and eligible for adjuvant chemotherapy, hormonotherapy and/or radiotherapy. They will be randomly allocated between one of four arms: (1) web-based connected device (evolving target number of daily steps and an individualised, semisupervised, adaptive programme of two walking and one muscle strengthening sessions per week in autonomy), (2) therapeutic patient education (one educational diagnosis, two collective educational sessions, one evaluation), (3) combination of both interventions and (4) control. All participants will receive the international physical activity recommendations. Assessments (baseline, 6 and 12 months) will include physical fitness tests, anthropometrics measures, body composition (CT scan, bioelectrical impedance), self-administered questionnaires (physical activity profile (Recent Physical Activity Questionnaire), quality of life (European Organization for Research and Treatment of Cancer Quality-Of-Life Questionnaire-30, EQ-5D-5L), fatigue (Piper Fatigue Scale-12), social deprivation (Evaluation of Deprivation and Inequalities in Health Examination Centres), lifestyle, physical activity barriers, occupational status) and biological parameters (blood draw)., Ethics and Dissemination: This study was reviewed and approved by the French Ethics Committee. The findings will be disseminated to the scientific and medical community via publications in peer-reviewed journals and conference presentations., Trial Registration Number: NCT03529383; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Sarcopenia has been identified as an important prognostic factor for patients with cancer. This study aimed at exploring the potential associations between a 6-month physical activity intervention and muscle characteristics, sarcopenia, oxidative stress and toxicities in patients with metastatic breast cancer., Methods: Women newly diagnosed with metastatic breast cancer (N = 49) participated in an unsupervised, personalized, 6-month physical activity intervention with activity tracker. Computerized tomography images at the third lumbar vertebra were analysed at baseline, three months and six months to assess sarcopenia (muscle mass index < 40 cm 2 /m 2 ) and muscle quality (poor if muscle attenuation < 37.8 Hounsfield Units). Oxidative markers included plasma antioxidant enzymes (catalase, glutathione peroxidase and superoxide dismutase activities), prooxidant enzymes (NADPH oxidase and myeloperoxidase activities) and oxidative stress damage markers (advanced oxidation protein products, malondialdehyde (MDA) and DNA oxidation., Results: At baseline 53% (mean age 55 years (SD 10.41)) were sarcopenic and 75% had poor muscle quality. Muscle cross sectional area, skeletal muscle radiodensity, lean body mass remained constant over the six months (p = 0.75, p = 0.07 and p = 0.75 respectively), but differed significantly between sarcopenic and non-sarcopenic patients at baseline and 6-months. Sarcopenic patients at baseline were more likely to have an increase of MDA (p = 0.02) at 6 months. Being sarcopenic during at least one moment during the 6-month study was associated with a higher risk of developing severe toxicities (grade > 2) (p = 0.02)., Conclusions: This study suggests potential benefits of physical activity for maintenance of muscle mass. Sarcopenia can alter many parameters and disturb the pro and antioxidant balance., (© 2021. The Author(s).)

Purpose: Regular physical activity (PA) can affect oxidative stress, known to be involved in carcinogenesis. The objective of this study was to evaluate the associations between a six-month PA intervention and oxidative stress biomarkers, PA, and clinical outcomes in patients with metastatic breast cancer., Methods: Forty-nine newly diagnosed patients with metastatic breast cancer were recruited for a single-arm, unsupervised, and personalized six-month walking intervention with activity tracker. PA level and PA fitness, plasma concentrations of DNA oxidation (8OhdG), lipid peroxidation (MDA), and protein oxidation (AOPP), plasma activities of superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase, plasma and leucocyte activities of myeloperoxidase (MPO) and NADPH oxidase (NOX), and clinical markers of tumor progression (RECIST criteria) were measured at baseline and after the six-month intervention., Results: GPX activity (+17%) and MDA (+9%) significantly increased between baseline and the end of the intervention. Changes in PA level and fitness were significantly positively correlated with changes in plasma GPX and significantly negatively with changes in NOX in the leucocytes. Plasma MDA was significantly higher (+20%) whereas plasma AOPP was lower (-46%) for patients with tumor progression or that died during the six months as compared to patients without progression., Conclusion: A six-month PA intervention may be potentially beneficial in metastatic breast cancer patients for enhancing antioxidant enzyme activity and decreasing prooxidant enzyme activity. Moreover, AOPP and MDA could also be favorable and unfavorable biomarkers, respectively, since they are associated with disease progression and fitness level in this population. This trial is registered with NCT number: NCT03148886., Competing Interests: No author reports any competing financial interest., (Copyright © 2021 Lidia Delrieu et al.)

Introduction: Older adults with cancer suffer from the combined effects of ageing, cancer disease and treatment side effects. The main treatment for patients with haematological malignancies is chemotherapy, associated with significant toxicities. Chemotherapy can alter patients' physical function and quality of life which are often already diminished in older patients due to ageing and comorbidities. It therefore seems essential to develop and to evaluate interventions capable of preventing physical and psychosocial decline and its consequences. Promoting physical activity is a promising approach to improve physical function and quality of life in older adults with cancer, but there are limited data on the feasibility of such interventions among older patients with haematological malignancies, concomitant to chemotherapy., Methods and Analysis: OCAPI (OnCogeriatric and Individualized Physical Activity) is a single-arm, interdisciplinary, prospective, interventional, feasibility study. It is intended to include 40 patients (20 patients with acute myeloid leukaemia and 20 patients with non-Hodgkin's lymphoma) over 65 years in an individualised 6-month physical activity programme. The programme consists of individually supervised exercise sessions with an increasing volume of physical activity either at home and/or in a laminar airflow room (depending on the disease and treatment regimen) followed by unsupervised sessions and phone follow-ups. Patients will receive an activity tracker during the 6 months of the programme. Evaluations will take place at inclusion and at 3, 6 and 12 months to assess the feasibility of the programme and to explore potential changes in physical, psychosocial and clinical outcomes. The results will generate preliminary data to implement a larger randomised controlled trial., Ethics and Dissemination: The study protocol was approved by the French ethics committee (Comité de protection des personnes Est I, N°ID-RCB 2019-A01231-56, 12 July 2019). All participants will have to sign and date an informed consent form. The findings will be disseminated in peer-reviewed journals and academic conferences., Trial Registration Number: NCT04052126., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The response to immunotherapy has been little investigated in overweight and obese cancer patients. We evaluated the relationships between BMI, toxicity, and survival in patients treated by immunotherapy for metastatic cancer. We included metastatic cancer patients treated by immunotherapy between January 2017 and June 2020 at the Centre Léon Bérard. In total, 272 patients were included: 64% men and 36% women, with a median age of 61.4 years. BMI ≥ 25 in 34.2% and 50% had non-small cell lung cancer ( n = 136). Most received monotherapy, with nivolumab in 41.9% and pembrolizumab in 37.9%. Toxicity, mostly dysthyroiditis, occurred in 41%. Median overall survival (OS), estimated by Kaplan-Meier analysis, was significantly longer for patients with a BMI ≥ 25 than for those with a BMI < 25 (24.8 versus 13.7 months HR = 0.63; 95% CI 0.44-0.92, p = 0.015), and for patients experiencing toxicity than for those without toxicity (NR versus 7.8 months, HR = 0.22; 95% CI 0.15-0.33, p < 0.001). Adjusted OS was associated with toxicity, and the occurrence of toxicity was associated with sex and histological features but not with BMI. Thus, being overweight and experiencing toxicity was associated with longer overall survival in patients treated by immunotherapy. More attention should be paid to body composition in the care of cancer patients.

Background: Physical activity (PA) is a modifiable lifestyle factor that can be targeted to increase energy expenditure and promote weight loss. However, the amount of PA required for weight loss remains inconsistent. Wearable activity trackers constitute a valuable opportunity to obtain objective measurements of PA and study large populations in real-life settings., Objective: We aim to study the associations of initial device-assessed PA characteristics (average step counts and step count variability) and their evolution with 6-month weight change., Methods: We analyzed data from 26,935 Withings-connected device users (wearable activity trackers and digital scales). To assess the initial PA characteristics and their 6-month changes, we used data recorded during the first and sixth 30-day periods of activity tracker use. For each of these periods, we used the monthly mean of daily step values as a proxy for PA level and derived the monthly coefficient of variation (CV) of daily step values to estimate PA level variability. Associations between initial PA characteristics and 6-month weight change were assessed using multivariable linear regression analyses controlled for age, sex, blood pressure, heart rate, and the predominant season. Restricted cubic spline regression was performed to better characterize the continuous shape of the associations between PA characteristics and weight change. Secondary analyses were performed by analyzing the 6-month evolution of PA characteristics in relation to weight change., Results: Our results revealed that both a greater PA level and lower PA level variability were associated with weight loss. Compared with individuals who were initially in the sedentary category (<5000 steps/day), individuals who were low active (5000-7499 steps/day), somewhat active (7500-9999 steps/day), and active (≥10,000 steps/day) had a 0.21-kg, a 0.52-kg, and a 1.17-kg greater decrease in weight, respectively (95% CI -0.36 to -0.06, -0.70 to -0.33, and -1.42 to -0.93, respectively). Compared with users whose PA level CV was >63%, users whose PA level CV ranged from 51% to 63%, 40% to 51%, and was ≤40%, had a 0.19-kg, a 0.23-kg, and a 0.33-kg greater decrease in weight, respectively (95% CI -0.38 to -0.01, -0.41 to -0.04, and -0.53 to -0.13, respectively). We also observed that each 1000 steps/day increase in PA level over the 6-month follow-up was associated with a 0.26-kg (95% CI -0.29 to -0.23) decrease in weight. No association was found between the 6-month changes in PA level variability and weight change., Conclusions: Our results add to the current body of knowledge that health benefits can be observed below the 10,000 steps/day threshold and suggest that not only increased mean PA level but also greater regularity of the PA level may play important roles in short-term weight loss., (©Douae El Fatouhi, Lidia Delrieu, Catherine Goetzinger, Laurent Malisoux, Aurélie Affret, David Campo, Guy Fagherazzi. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 15.04.2021.)

Breast cancer (BC) remains complex for women both physically and psychologically. The objectives of this study were to (1) assess the evolution of the main sequelae and treatment two and five years after diagnosis in women with early-stage breast cancer, (2) explore patterns of sequelae associated with given sociodemographic, clinical, and lifestyle factors. The current analysis was based on 654 localized BC patients enrolled in the French nationwide longitudinal survey "vie après cancer" VICAN (January-June 2010). Information about study participants was collected at enrollment, two and five years after diagnosis. Changes over time of the main sequelae were analyzed and latent class analysis was performed to identify patterns of sequelae related to BC five years after diagnosis. The mean age (±SD) of study participants at inclusion was 49.7 (±10.5) years old. Six main classes of sequelae were identified two years and five years post-diagnosis (functional, pain, esthetic, fatigue, psychological, and gynecological). A significant decrease was observed for fatigue ( p = 0.03) and an increase in cognitive sequelae was reported ( p = 0.03). Two latent classes were identified-functional and esthetic patterns. Substantial sequelae remain up to five years after BC diagnosis. Changes in patient care pathways are needed to identify BC patients at a high risk.

Purpose: Exercise has been shown to improve physical and psychological conditions during cancer therapy, but mechanisms remain poorly understood. The purpose of the present study was to report the results of cancer-related biomarkers and metabolomics outcomes from the PASAPAS feasibility study., Methods: In the PASAPAS randomized controlled trial, 61 women beginning adjuvant chemotherapy for localized breast cancer were randomized in a 6-month program of weekly aerobic exercises associated with nutritional counseling versus usual care with nutritional counseling. In the present analysis of 58 women for whom blood samples were available, first, circulating levels of biomarkers (ie, insulin, insulin-like growth factor 1, estradiol, adiponectin, leptin, interleukin-6, and tumor necrosis factor α) were measured at baseline and 6-month follow-up. Changes in biomarkers were compared between exercisers (n = 40) and controls (n = 18) using mixed-effect models. Second, serum metabolites were studied using an untargeted 1 H nuclear magnetic resonance spectroscopy, and orthogonal partial least squares analyses were performed to discriminate exercisers and controls at baseline and at 6 months., Results: Over the 6-month intervention, no statistically significant differences were observed between exercisers and controls regarding changes in biomarkers and metabolomic profiles., Conclusion: The present analysis of the PASAPAS feasibility trial did not reveal any improvement in circulating biomarkers nor identified metabolic signatures in exercisers versus controls during adjuvant breast cancer treatment. Larger studies preferably in women with poor physical activity level to avoid ceiling effect, testing different doses and types of exercise on additional biological pathways, could allow to clarify the mechanisms mediating beneficial effects of physical exercise during cancer treatment., Trial Registration: ClinicalTrials.gov Identifier: NCT01331772. Registered 8 April 2011, https://clinicaltrials.gov/ct2/show/NCT01331772?term=pasapas&rank=1.

Background: Patients with a metastatic breast cancer suffer from a deteriorated health-related quality of life and numerous symptoms such as pain, severe fatigue and a decrease of their physical fitness. As the feasibility of a physical activity program has been demonstrated in this population, ABLE02 aims to assess the efficacy of a 6 month-physical activity program using connected devices to improve health-related quality of life and to reduce fatigue in women with metastatic breast cancer., Methods: ABLE02 is a prospective, national, multicenter, randomized, controlled and open-label study. A total of 244 patients with a metastatic breast cancer, with at least one positive hormone receptor and a first-line chemotherapy planned, will be randomly assigned (1:1 ratio) to: (i) the intervention arm to receive physical activity recommendations, an activity tracker to wear 24 h a day during the whole intervention (6 months) with at least three weekly walking sessions and quizzes each week on physical activity and nutrition (ii) the control arm to receive physical activity recommendations only. Health-related quality of life will be assessed every 6 weeks and main assessments will be conducted at baseline, M3, M6, M12 and M18 to evaluate the clinical, physical, biological and psychological parameters and survival of participants. All questionnaires will be completed on a dedicated application., Discussion: An activity program based on a smartphone application linked to an activity tracker may help to improve quality of life and reduce fatigue of patients with a metastatic breast cancer. The growth of e-health offers the opportunity to get real-time data as well as improving patient empowerment in order to change long-term behaviors., Trial Registration: NCT number: NCT04354233 .

Benefits of physical activity are widely demonstrated for early stage cancers but few studies have focused on metastatic disease. The purpose of this study was to determine the impact of physical activity on survival in patients with metastatic breast cancer. We conducted a secondary analysis of the national, multicentric, non-randomized, prospective cohort SNPs to Risk of Metastasis (StoRM) study. The level of physical activity was self-reported at inclusion and divided into three categories of physical activity: light level, moderate level, and vigorous level. Overall, 833 patients (56.2%) completed the physical activity questionnaire at baseline on average physical activity during the previous year: 11.6% had a light level of physical activity, 69.0% achieved moderate levels of physical activity and 19.3% reported vigorous levels of physical activity. After adjustment for confounding, physical activity was not statistically significantly associated with overall survival in the whole population. Subgroup analysis identified that both vigorous and moderate physical activity were associated with statistically significantly improved overall survival compared to light physical activity level only in the HER2 positive subgroup (HR 0.23; 95% CI 0.07-0.70, p = 0.01 and HR 0.38; 95% CI 0.15-0.96, p = 0.04). Physical activity done during the previous year was associated with survival in HER2 positive metastatic breast cancer patients. These results suggest that overall survival in metastatic breast cancer patients could be improved through physical activity which should be considered as a complementary intervention for these individuals. The study showed that moderate/vigorous levels of physical activity were associated with better overall survival, and that these associations remained statistically significant in multivariate analysis in the HER2 positive subgroup. These results have clinical relevance and justify the recommendations for physical activity interventions in metastatic breast cancer.

Background: There is limited knowledge regarding the potential benefits of physical activity in patients with metastatic breast cancer., Objective: The Advanced stage Breast cancer and Lifestyle Exercise (ABLE) Trial aimed to assess the feasibility of a physical activity intervention in women with metastatic breast cancer and to explore the effects of physical activity on functional, psychological, and clinical parameters., Methods: The ABLE Trial was a single-arm, 6-month intervention study with a home-based, unsupervised, and personalized walking program using an activity tracker. At baseline and 6 months, we assessed anthropometrics, functional fitness, physical activity level, sedentary behavior, quality of life, fatigue, and tumor progression. Paired proportions were compared using the McNemar test and changes of parameters during the intervention were analyzed using the Wilcoxon signed-rank test, the Mann-Whitney test, and Spearman rank correlations., Results: Overall, 49 participants (mean age 55 years; recruitment rate 94%) were enrolled and 96% adhered to the exercise prescription (attrition rate 2%). Statistically significant improvements in the 6-minute walking distance test (+7%, P<.001) and isometric quadriceps strength (+22%, P<.001), as well as decreases in body mass index (-2.5%, P=.03) and hip circumference (-4.0%, P<.001) were observed at 6 months. Quality of life remained stable and a nonstatistically significant decrease (-16%, P=.07) in fatigue was observed., Conclusions: The high recruitment and adherence rates suggest the willingness of patients with metastatic breast cancer to participate in a physical activity program. The beneficial outcomes regarding physical fitness and anthropometry of this unsupervised physical activity program may encourage these patients to maintain a physically active lifestyle. Future randomized controlled trials with larger sample sizes are warranted., Trial Registration: ClinicalTrials.gov NCT03148886; https://clinicaltrials.gov/ct2/show/NCT03148886., (©Lidia Delrieu, Vincent Pialoux, Olivia Pérol, Magali Morelle, Agnès Martin, Christine Friedenreich, Olivia Febvey-Combes, David Pérol, Elodie Belladame, Michel Clémençon, Eva Roitmann, Armelle Dufresne, Thomas Bachelot, Pierre Etienne Heudel, Marina Touillaud, Olivier Trédan, Béatrice Fervers. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 28.01.2020.)

Multicystic renal dysplasia is a congenital cystic anomaly of the kidney caused by abnormal metanephric differentiation with immature tubules. It is surrounded by mesenchymal collars and islands of immature mesenchyma present between the cysts. The PI3K-AKT-mTOR signaling pathway is a key regulator involved in cell growth, proliferation, motility, survival, and apoptosis. Activation of the PI3K-AKT-mTOR pathway results in the survival and proliferation of tumor cells in many cancers. The aim of this study is to analyze the topographic expression of phospho-AKT, phospho-mTOR, and phospho-70S6K in renal development and in the multicystic dysplastic kidney (MCDK). A total of 17 fetal kidneys of development age from the first to the third trimester and 13 cases of pathological kidneys with MCDK were analyzed by immunohistochemistry in order to evaluate the expression of phospho-AKT (S473), phospho-mTOR, and phospho-70S6K. Phospho-AKT and phospho-mTOR were expressed early in renal development and in an identical manner for every structure derived from the ureteric bud, such as collecting ducts and urothelium. Phospho-p70S6K was expressed early in the urothelium and in glomerular mesangial cells. Later, their expressions differed according to the needs of cell proliferation and differentiation over time by becoming more selective. In MCDK, phospho-AKT, phospho-mTOR, and phospho-70S6K have the same profile: a high cytoplasmic expression in cystic epithelium, loose mesenchyma, and primitive tubes. This study demonstrates the essential and specific role of the PI3K-AKT-mTOR pathway in the formation of cysts in multicystic renal dysplasia., (© 2020 S. Karger AG, Basel.)

Objective: This secondary analysis of the ABLE Trial (ClinicalTrials.gov NCT03148886) aimed to assess physical activity preferences before and after a 6-month physical activity intervention for women recently diagnosed with metastatic breast cancer and to investigate demographic and clinical correlates of these preferences., Methods: Forty-nine patients participated in the ABLE Trial, a single-arm, unsupervised 6-month physical activity intervention with activity trackers. At baseline and 6 months, physical activity preferences, physical activity level, clinical variables, demographics and social vulnerability were assessed., Results: At baseline, 49 participants were included, among whom 85% were interested in receiving physical activity counselling and 89% were interested in following a physical activity programme designed for metastatic breast cancer. At the end of the study, more participants preferred practising in a community fitness centre (66%) rather than at home (19% vs. 44% at baseline, p = .03). A higher social vulnerability score and not being treated by chemotherapy at baseline were significantly associated with lower desire to receive physical activity counselling (p = .01 and p = .04 respectively)., Conclusions: This study will help design future studies within patients with metastatic breast cancer in accordance with their preferences. Designing tailored physical activity interventions according to the participant's preferences may be one key to success for adherence., (© 2019 John Wiley & Sons Ltd.)

Background: About 5% of breast cancer cases are metastatic at diagnosis, and 20%-30% of localized breast cancer cases become secondarily metastatic. Patients frequently report many detrimental symptoms related to metastasis and treatments. The physical, biological, psychological, and clinical benefits of physical activity during treatment in patients with localized breast cancer have been demonstrated; however, limited literature exists regarding physical activity and physical activity behavior change in patients with metastatic breast cancer., Objective: The primary objective of this study is to assess the feasibility of a 6-month physical activity intervention with activity trackers in patients with metastatic breast cancer (the Advanced stage Breast cancer and Lifestyle Exercise, ABLE Trial). Secondary objectives are to examine the effects of physical activity on physical, psychological, anthropometrics, clinical, and biological parameters., Methods: We plan to conduct a single-center, single-arm trial with 60 patients who are newly diagnosed with metastatic breast cancer. Patients will receive an unsupervised and personalized 6-month physical activity program that includes an activity tracker Nokia Go and is based on the physical activity recommendation. Patients will be encouraged to accumulate at least 150 minutes per week of moderate-to-vigorous intensity physical activity. Baseline and 6-month assessments will include anthropometric measures, functional tests (eg, 6-minute walk test and upper and lower limb strength), blood draws, patient-reported surveys (eg, quality of life and fatigue), and clinical markers of tumor progression (eg, Response Evaluation Criteria In Solid Tumors criteria)., Results: Data collection occurred between October 2016 and January 2018, and the results are expected in August 2018., Conclusions: The ABLE Trial will be the first study to assess the feasibility and effectiveness of an unsupervised and personalized physical activity intervention performed under real-life conditions with activity trackers in patients with metastatic breast cancer., Trial Registration: ClinicalTrials.gov NCT03148886; https://clinicaltrials.gov/ct2/show/NCT03148886 (Accessed by WebCite at http://www.webcitation.org/71yabi0la)., Registered Report Identifier: RR1-10.2196/10487., (©Lidia Delrieu, Olivia Pérol, Béatrice Fervers, Christine Friedenreich, Jeff Vallance, Olivia Febvey-Combes, David Pérol, Brice Canada, Eva Roitmann, Armelle Dufresne, Thomas Bachelot, Pierre-Etienne Heudel, Olivier Trédan, Marina Touillaud, Vincent Pialoux. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 30.08.2018.)

Background: Sleep is a modifiable lifestyle factor that can be a target for efficient intervention studies to improve the quality of life and decrease the risk or burden of some chronic conditions. Knowing the profiles of individuals with poor sleep patterns is therefore a prerequisite. Wearable devices have recently opened new areas in medical research as potential efficient tools to measure lifestyle factors such as sleep quantity and quality., Objectives: The goal of our research is to identify the determinants of poor sleep based on data from a large population of users of connected devices., Methods: We analyzed data from 15,839 individuals (13,658 males and 2181 females) considered highly connected customers having purchased and used at least 3 connected devices from the consumer electronics company Withings (now Nokia). Total and deep sleep durations as well as the ratio of deep/total sleep as a proxy of sleep quality were analyzed in association with available data on age, sex, weight, heart rate, steps, and diastolic and systolic blood pressures., Results: With respect to the deep/total sleep duration ratio used as a proxy of sleep quality, we have observed that those at risk of having a poor ratio (≤0.40) were more frequently males (odds ratio [OR] female vs male =0.45, 95% CI 0.38-0.54), younger individuals (OR >60 years vs 18-30 years =0.47, 95% CI 0.35-0.63), and those with elevated heart rate (OR >78 bpm vs ≤61 bpm =1.18, 95% CI 1.04-1.34) and high systolic blood pressure (OR >133 mm Hg vs ≤116 mm Hg =1.22, 95% CI 1.04-1.43). A direct association with weight was observed for total sleep duration exclusively., Conclusions: Wearables can provide useful information to target individuals at risk of poor sleep. Future alert or mobile phone notification systems based on poor sleep determinants measured with wearables could be tested in intervention studies to evaluate the benefits., (©Guy Fagherazzi, Douae El Fatouhi, Alice Bellicha, Amin El Gareh, Aurélie Affret, Courtney Dow, Lidia Delrieu, Matthieu Vegreville, Alexis Normand, Jean-Michel Oppert, Gianluca Severi. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 23.10.2017.)