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Background Diffuse large B cell lymphoma (DLBCL) is an aggressive disease. The first-line treatment is well defined in young patients, however in oldest old patients treatment remains unclear. Objectives To investigate the impact of therapeutics management and geriatric evaluation on survival in aged patients with DLBCL. Methods We performed a systematic review of PUBMED and COCHRANE databases of published report on elderly patients (median age 80 and above) with DLBCL, from January 2002 to January 2020. Results We included 32 studies (6 prospective and 26 retrospective). Patients treated with anthracyclines-containing chemoimmunotherapy had a two-years overall survival (OS) of 59% to 74.3% in prospective studies, and 48.1 to 64.6% in retrospective studies. With less intensive treatment without anthracyclines, two-years OS was 28% to 53%. Without specific treatment, median OS was two months. History of falls and severe comorbidities were associated with a decrease survival. Conclusions Chemoimmunotherapy with anthracyclines increase survival in selected very elderly patients in compared to less intensive regimen. Geriatric assessment, in particular altered mobility disorders and severe comorbidities, are predictive of survival and should be associated to the therapeutic decision. More comparative studies are needed to guide the management of frailer patients.

Objective Hematological treatment decisions in older adults with hematological malignancies are complex. Our objective is to study the impact of a comprehensive geriatric assessment on hematological treatment decision in older patients and the factors associated with change in treatment plan. Methods We conducted a cross-sectional analysis of patients aged 65 years and above with hematological malignancies, hospitalized between 2008 and 2019 at the University Cancer Institute of Toulouse. They were assessed by a geriatrician/nurse team using a comprehensive geriatric assessment (CGA). A penalized logistic regression model with elastic net regularization was used to identify factors associated with change in hematological treatment plan. Results A total of 424 patients were included. Main hematological malignancies were lymphoma (36.1 %), acute myeloid leukemia (26.9 %) and myelodysplastic syndrome (19.8%). Change in hematological treatment plan was suggested after CGA for 92 patients (21.7%). Factors associated with change in treatment plan were functional impairment according to ADL and IADL scale, mobility impairment, the presence of comorbidity defined by the Charlson score > 1 and increasing age. Conclusion A CGA has a significant impact on hematological treatment decision in older patients. Functional and mobility impairment, comorbidities and age are predictive factors of change in treatment plan.

International audience; Objectives: To evaluate the impact of neutralizing monoclonal antibody (mAb) treatment and to determine whether the selective pressure of mAbs could facilitate the proliferation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with spike protein mutations that might attenuate mAb effectiveness.Patients and methods: We evaluated the impact of mAbs on the nasopharyngeal (NP) viral load and virus quasispecies of mAb-treated patients using single-molecule real-time sequencing. The mAbs used were: Bamlanivimab alone (four patients), Bamlanivimab/Etesevimab (23 patients) and Casirivimab/Imdevimab (five patients).Results: The NP SARS-CoV-2 viral load of mAb-treated patients decreased from 8.2 log10 copies/mL before administration to 4.3 log10 copies/mL 7 days after administration. Five immunocompromised patients given Bamlanivimab/Etesevimab were found to have mAb activity-reducing spike mutations. Two patients harboured SARS-CoV-2 variants with a Q493R spike mutation 7 days after administration, as did a third patient 14 days after administration. The fourth patient harboured a variant with a Q493K spike mutation 7 days post-treatment, and the fifth patient had a variant with a E484K spike mutation on day 21. The emergence of the spike mutation was accompanied by stabilization or rebound of the NP viral load in three of five patients.Conclusion: Two-mAb therapy can drive the selection of resistant SARS-CoV-2 variants in immunocompromised patients. Patients given mAbs should be closely monitored and measures to limit virus spread should be reinforced.

Background: This systematic review aimed at comparing performances of ultrasonography (US), magnetic resonance imaging (MRI), and fluorodeoxyglucose positron emission tomography (PET) for axillary staging, with a focus on micro- or micrometastases. Methods: A search for relevant studies published between January 2002 and March 2018 was conducted in MEDLINE database. Study quality was assessed using the QUality Assessment of Diagnostic Accuracy Studies checklist. Sensitivity and specificity were meta-analyzed using a bivariate random effects approach; Results: Across 62 studies (n = 10,374 patients), sensitivity and specificity to detect metastatic ALN were, respectively, 51% (95% CI: 43–59%) and 100% (95% CI: 99–100%) for US, 83% (95% CI: 72–91%) and 85% (95% CI: 72–92%) for MRI, and 49% (95% CI: 39–59%) and 94% (95% CI: 91–96%) for PET. Interestingly, US detects a significant proportion of macrometastases (false negative rate was 0.28 (0.22, 0.34) for more than 2 metastatic ALN and 0.96 (0.86, 0.99) for micrometastases). In contrast, PET tends to detect a significant proportion of micrometastases (true positive rate = 0.41 (0.29, 0.54)). Data are not available for MRI. Conclusions: In comparison with MRI and PET Fluorodeoxyglucose (FDG), US is an effective technique for axillary triage, especially to detect high metastatic burden without upstaging majority of micrometastases.

The WHO action plan on aging expects to change current clinical practices by promoting a more personalized model of medicine. To widely promote this initiative and achieve this goal, healthcare professionals need innovative monitoring tools. Use of conventional biomarkers (clinical, biological or imaging) provides a health status assessment at a given time once a capacity has declined. As a complement, continuous monitoring thanks to digital biomarkers makes it possible to remotely collect and analyze real life, ecologically valid, and continuous health related data. A seamless assessment of the patient’s health status potentially enables early diagnosis of IC decline (e.g. sub-clinical or transient events not detectable by episodic evaluations) and investigation of its probable causes. This narrative review aims to develop the concept of digital biomarkers and its implementation in IC monitoring.

Background: Frailty and cognitive impairment are common manifestations of the ageing process and are closely related. But the mechanisms linking aging, physical frailty, and cognitive disorders, are complex and remain unclear. Objectives: We aim to explore the role of cerebral amyloid pathology, but also a range of nutritional, physical, biological or brain-aging marker in the development of cognitive frailty. Method: COGFRAIL study is a monocentric prospective study of frail older patients with an objective cognitive impairment (Clinical Dementia Rating Scale global score at 0.5 or 1). Three-hundred-and-twenty-one patients are followed up every 6 months, for 2 years. Clinical assessment at baseline and during follow-up included frailty, physical, mood, sensory, nutritional, and cognitive assessment (with a set of neuropsychological tests). Cerebral amyloid pathology is measured by amyloid Positron Emission Tomography (PET) or amyloid-β-1-42 level in cerebrospinal fluid. Brain magnetic resonance imaging, measurement of body composition using Dual X Ray Absorptiometry and blood sampling are performed. The main outcome of the study is to assess the prevalence of positive cerebral amyloid status according to amyloid PET or amyloid-β-1-42 level CSF. Secondary outcomes included biological, nutritional, MRI imaging, cognitive, clinical, physical and body composition markers to better understand the mechanisms of cognitive frailty. Perspective: COGFRAIL study will give the opportunity to better understand the link between Gerosciences, frailty, cognitive impairment, and Alzheimer’s disease, and to better characterize the physical and cognitive trajectories of frail older adults according to their amyloid status. Understanding the relationship between physical frailty and cognitive impairment is a prerequisite for the development of new interventions that could prevent and treat both conditions.

(1) Background: COVID-19 has become a global pandemic and older patients present higher mortality rates. However, studies on the characteristics of this population set are limited. The objective of this study is to describe clinical characteristics and outcomes of older patients hospitalized with COVID-19. (2) Methods: This retrospective cohort study was conducted from March to May 2020 and took place in three acute geriatric wards in France. Older patients hospitalized for COVID-19 infections were included. We collected clinical, radiological, and laboratory outcomes. (3) Results: Ninety-four patients were hospitalized and included in the final analysis. Mean age was 85.5 years and 55% were female. Sixty-four (68%) patients were confirmed COVID-19 cases and 30 (32%) were probable. A majority of patients were dependent (77%), 45% were malnourished, and the mean number of comorbidities was high in accordance with the CIRS-G score (12.3 &plusmn, 25.6). The leading causes of hospitalization were fever (30%), dyspnea (28%), and geriatric syndromes (falls, delirium, malaise) (18%). Upon follow-up, 32% presented acute respiratory failure and 30% a geriatric complication. Frailty and geriatric characteristics were not correlated with mortality. Acute respiratory failure (p = 0.03) and lymphopenia (p = 0.02) were significantly associated with mortality. (4) Conclusions: Among older patients hospitalized with COVID-19, clinical presentations were frequently atypical and complications occurred frequently. Frailty and geriatric characteristics were not correlated with mortality.

Background Half of cancer cases occur in patients aged 70 and above. Majority of older patients are eligible for chemotherapy but evidence for treating this population is sparse and severe toxicities affect more than half of them. Determining prognostic biomarkers able to predict poor chemotherapy tolerance remains one of the major issues in geriatric oncology. Ageing is associated with body composition changes (increase of fat mass and loss of lean mass) independently of weight-loss. Previous studies suggest that body composition parameters (particularly muscle mass) may predict poor chemotherapy tolerance. However, studies specifically including older adults on this subject remain sparse and the majority of them study body composition based on computed tomography (CT) scanner (axial L3 section) muscle mass estimation. This method is to date not validated in elderly cancer patients. Methods This trial (Fraction) will evaluate the discriminative ability of appendicular lean mass measured by dual-energy X-ray absorptiometry (DXA) to predict severe toxicity incidence in older cancer-patients treated with first-line chemotherapy. DXA is considered the gold standard in body composition assessment in older adults. Patient’s aged ≥70 diagnosed with solid neoplasms or lymphomas at a locally advanced or metastatic stage treated for first-line chemotherapy were recruited. Patients completed a pre-chemotherapy assessment that recorded socio-demographics, tumor/treatment variables, laboratory test results, geriatric assessment variables (function, comorbidity, cognition, social support and nutritional status), oncological risk scores and body composition with DXA. Appendicular lean mass was standardized using evidence based international criteria. Participants underwent short follow-up geriatric assessments within the first 3 months, 6 months and a year after inclusion. Grade 3 to 5 chemotherapy-related toxicities, as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) were assessed at each chemotherapy cycle. Discussion The finding that body composition is associated with poor tolerance of chemotherapy could lead to consider these parameters as well as improve current decision-making algorithms when treating older adults. Trial registration ClinicalTrials.gov Identifier: NCT02806154 registered on October 2016.

Background Frailty and hemoglobin concentration, above what would be considered clinical anemia, are two common findings in older patients that lead to an increased risk of negative health outcomes. The objective of this study is to evaluate whether hemoglobin concentration is an independent predictor of frailty and investigate possible causal pathways with a focus on the relationship between inflammation or nutrition and hemoglobin concentration. Methods 1829 community-dwelling participants aged 65 years or older who visited the Toulouse frailty day hospital during 2011 and 2016 were included in this analysis. Patients underwent a comprehensive geriatric assessment and had a blood sample taken. A series of multivariate logistic regression models were performed after minimizing potential influence from age, gender, kidney function, inflammation, cognition, nutritional status and certain socio-economic factors. Results Hemoglobin concentration and frailty are significantly associated after minimizing potential influence from other covariates (p p > 0.005). Conclusions Hemoglobin concentration is strongly associated with frailty in older adults. These results can have potentially important implications for prevention policies targeting frailty by identifying potential patients with high risk of adverse outcomes and functional outcomes.

Background The comprehensive geriatric assessment (CGA) is the gold standard in geriatric oncology to identify patients at high risk of adverse outcomes and optimize cancer and overall management. Many studies have demonstrated that CGA could modify oncologic treatment decision. However, there is little knowledge on which domains of the CGA are associated with this change. Moreover, the impact of frailty and physical performance on change in cancer treatment plan has been rarely assessed. Methods This is a cross-sectional study of older patients with solid or hematologic cancer referred by oncologists for a geriatric evaluation before cancer treatment. A comprehensive geriatric assessment was performed by a multidisciplinary team to provide guidance for treatment decision. We performed a multivariate analysis to identify CGA domains associated with change in cancer treatment plan. Results Four hundred eighteen patients, mean age 82.8 ± 5.5, were included between October 2011 and January 2016, and 384 of them were referred with an initial cancer treatment plan. This initial cancer treatment plan was changed in 64 patients (16.7%). In multivariate analysis, CGA domains associated with change in cancer treatment plan were cognitive impairment according to the MMSE score (p = 0.020), malnutrition according to the MNA score (p = 0.023), and low physical performance according to the Short Physical Performance Battery (p = 0.010). Conclusion Cognition, malnutrition and low physical performance are significantly associated with change in cancer treatment plan in older adults with cancer. More studies are needed to evaluate their association with survival, treatment toxicity and quality of life. The role of physical performance should be specifically explored.

BACKGROUND Recent WHO reports, propose wearable devices to collect information on activity and walking speed as innovative health indicators. However, mainstream consumer-grade tracking devices and smartphone apps are often inaccurate and require long-term acceptability assessment. OBJECTIVE Our aim was to assess user acceptability of an instrumented shoe insole in frail older adults. This device monitors participants walking speed and differentiates active walking from shuffling after step length calibration. METHODS A multi-phase evaluation has been designed: (i) nine older adults were evaluated in a living lab for a day and three older adults were evaluated at home for a month; (ii) a randomized trial included 35 older adults at home for three months. A qualitative research design using face to face and phone semi-structured interviews was performed. Our hypothesis was that this insole was acceptable in long-term walking monitoring .The primary outcome was participants acceptability, measured by a qualitative questionnaire and average time of insole wearing per day. The secondary outcome described frailty evolution in both groups. RESULTS Living lab results confirmed the importance of a multi-phase design study with participant involvement. Participants proposed insole modifications. Overall acceptability had mixed results: low scores for reliability (2.1 over 6) and high scores for usability (4.3 over 6) outcomes. During the field test (mean age 79 years old), a majority of participants were very or quite satisfied with the insoles comfort at the end of follow-up (10 and 3 over 16). Participant insole acceptability evolved as follow: 63% at one month (12 over 19), 50% at two months (9 over 18), and 75% at three months (12 over 16). Nine participants in the intervention group discontinued the intervention because of technical issues. All participants equipped for more than a week reported wearing the insole every day at one month, 83% at two months (15 over 18) and 94% at three (15 over 16), for 5.8, 6.3 and 5.1 hours a day respectively. Insole data confirmed that participants effectively wore the insole without significant decline during follow-up, on average 13.5 days a month and 5.6 hours a day. For secondary endpoints, the change in frailty parameters did not differ for those randomly assigned to intervention group compared to usual care. CONCLUSIONS Our study reports acceptability data on an instrumented insole in indoor and outdoor walking with remote monitoring in frail older adults under real life conditions. To date, there is limited data in this population set. This thin instrumentation including a flexible battery, was a technical challenge, and seems to provide an acceptable solution over time and is valued by participants. However, users still raise certain acceptability issues. Given growing interest in wearable health care devices, these results will be useful for future developments. CLINICALTRIAL ClinicalTrials.gov NCT02316600

A consensual and operational definition of frailty is necessary in geriatric oncology. While many studies have focused on geriatric syndromes evaluated in the comprehensive geriatric assessment (CGA) to select patients at higher risk of poor outcomes, few have compared CGA data with Fried's phenotype of frailty, the most consensual measurement of frailty in geriatrics. Our objective was to determine a threshold of impaired domains evaluated in CGA associated with Frailty status.A cross-sectional study including all patients with cancer, evaluated from January 2011 to February 2016 at the Geriatric Frailty Clinic, Toulouse. A CGA was performed evaluating seven geriatric domains. Frailty was measured by Fried's phenotype to classify patients into three groups (robust/pre-frail/frail). We plotted a ROC curve to determine the threshold of impaired domains associated with frailty according to Fried.We included 418 patients aged 82.8 years (range 66-100 years). Thirty-three patients (7.9%) were robust, 155 (37.1%) pre-frail and 230 (55%) frail. There was a significant difference in ADL, IADL, nutrition, cognition and polypharmacy between the three groups (p .001 for each domain). Frail patients had more impaired geriatric domains on CGA than pre-frail and robust patients (respectively 4.5 ± 1.5, 2.8 ± 1.6 and 2.1 ± 1.2; p .001). The threshold of 4 impaired geriatric domains associated with Fried's Frailty status was identified (Se 77.39%, Sp 67.55%). Area under the curve was 79.6%.The phenotype of frailty is associated with more impaired geriatric domains and a threshold of 4 altered domains could be used to detect frailty from CGA data.