Early morning immune checkpoint blockade and overall survival of patients with metastatic cancer: An In-depth chronotherapeutic study.

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.

Quality of life among French breast cancer survivors in comparison with cancer-free women: the Seintinelles study.

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 Chi2 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.

Compliance with public health recommendations of cancer-free female research volunteers: the French Seintinelles study.

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.

Health behaviour changes in female cancer survivors: The Seintinelles study.

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.

Association between Nutritional Status and Treatment Response and Survival in Patients Treated with Immunotherapy for Lung Cancer: A Retrospective French Study.

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.

Pregnancy, fertility concerns and fertility preservation procedures in a national study of French breast cancer survivors.

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.

Digital phenotyping in young breast cancer patients treated with neoadjuvant chemotherapy (the NeoFit Trial): protocol for a national, multicenter single-arm trial.

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.

Effect of acute aerobic exercise before immunotherapy and chemotherapy infusion in patients with metastatic non-small-cell lung cancer: protocol for the ERICA feasibility trial.

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.

Variation over time of the factors influencing return to work and work capacities after a diagnosis of breast cancer: a study on the behalf of the Seintinelles research network.

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.

Impact of Limited E-Health Literacy on the Overall Survival of Patients With Cancer.

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.

Effectiveness of an individualized home-based physical activity program in surgery-free non-endarterectomized asymptomatic stroke patients: a study protocol for the PACAPh interventional randomized trial.

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.

Implementation of a Prevention Program Based on Adapted Physical Activity and Recommendations for Adolescents and Young Adults with Cancer: PREVAPAJA Study.

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.

Interest and preferences for physical activity programming and counselling among cancer patients aged over 70 years receiving oncological treatments.

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.

Connected device and therapeutic patient education to promote physical activity among women with localised breast cancer (DISCO trial): protocol for a multicentre 2×2 factorial randomised controlled trial.

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.

Impact of Physical Activity on Oxidative Stress Markers in Patients with Metastatic Breast Cancer.

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.

Association between Body Mass Index and Survival Outcome in Metastatic Cancer Patients Treated by Immunotherapy: Analysis of a French Retrospective Cohort.

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.

Individualised physical activity programme in patients over 65 years with haematological malignancies (OCAPI): protocol for a single-arm feasibility trial.

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.

Sarcopenia and serum biomarkers of oxidative stress after a 6-month physical activity intervention in women with metastatic breast cancer: results from the ABLE feasibility trial.

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 cm2/m2) 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.