Increased levels of GM-CSF and CXCL10 and low CD8+ memory stem T Cell count are markers of immunosenescence and severe COVID-19 in older people.

BACKGROUND: Ageing leads to altered immune responses, resulting in higher susceptibility to certain infections in the elderly. Immune ageing is a heterogeneous process also associated with inflammaging, a low-grade chronic inflammation. Altered cytotoxic T cell responses and cytokine storm have previously been described in severe COVID-19 cases, however the parameters responsible for such immune response failures are not well known. The aim of our study was to characterize CD8+ T cells and cytokines associated with ageing, in a cohort of patients aged over 70 years stratified by COVID-19 severity. RESULTS: One hundred and four patients were included in the study. We found that, in older people, COVID-19 severity was associated with (i) higher level of GM-CSF, CXCL10 (IP-10), VEGF, IL-1ß, CCL2 (MCP-1) and the neutrophil to lymphocyte ratio (NLR), (ii) increased terminally differentiated CD8+T cells, and (ii) decreased early precursors CD8+ T stem cell-like memory cells (TSCM) and CD27+CD28+. The cytokines mentioned above were found at higher concentrations in the COVID-19+ older cohort compared to a younger cohort in which they were not associated with disease severity. CONCLUSIONS: Our results highlight the particular importance of the myeloid lineage in COVID-19 severity among older people. As GM-CSF and CXCL10 were not associated with COVID-19 severity in younger patients, they may represent disease severity specific markers of ageing and should be considered in older people care.

Prognostic impact of neurocognitive disorders in older patients with cancer: the ELCAPA prospective cohort study.

OBJECTIVE: To assess the prognostic value of neurocognitive disorder (NCD) for 12 month-overall mortality in patients aged 70 or more with a solid cancer. DESIGN: prospective, observational, multicenter cohort. SETTING AND PARTICIPANTS: We analyzed data from the ELCAPA longitudinal multicenter observational cohort of patients aged 70 or over, referred for a geriatric assessment (GA) before a new cancer treatment modality between January 31st, 2007, and December 29th, 2017. We defined the baseline NCD in four classes: no NCD, mild NCD, moderate NCD, and major NCD, based on the Mini-Mental State Examination (MMSE) score, memory complaint, and the Instrumental Activities of Daily Living (IADL) score. STATISTICAL METHODS: We compared the baseline characteristics of patients according to NCD classes, globally and by pairs (with Bonferroni' correction). Prognosis value of NCD classes were analysed by using univariable and then multivariable 12 month survival analysis with age as time-variable and with and without adjustement for the treatment strategy (curative, palliative or exclusive supportive care). RESULTS: 2784 patients with solid-cancer were included, with a median [interquartile range] age of 82 [78;86]. 36% of the patients were free of NCD, 34% had a mild NCD, 17% had a moderate NCD, and 13% had a major NCD. We identified the following independent prognostic factors for 12 month-overall mortality: NCD (adjusted hazard ratio (aHR) [95% confidence interval (CI)] for a major NCD = 1.54 [1.19-1.98] (p < 0.001), type of cancer, metastatic status, inpatient consultation, poor general health (assessed as the level of fatigue and Eastern Cooperative Oncology Group performance status [ECOG-PS]), greater weight loss, palliative treatment, and exclusive supportive care. Additional adjustment for the treatment strategy did not greatly change the strength of the association of a major NCD with 12 month-overall mortality (HR [95%CI] = 1.78 [1.39-2.29] (p < 0.001). CONCLUSION: Our results suggest that the presence of a major NCD has direct prognostic value (independently of other geriatric factors, the type of cancer and the treatment strategy) in older patients with a solid cancer.

Geriatric assessment and quality of life for 2 years in older patients with head and neck cancer.

Due to the location and toxicity of treatments, head and neck cancer (HNC) has a major impact on quality of life (QoL). Objective: to assess the effects of geriatric-assessment (GA)-driven interventions on QoL over 2 years in older adults with HNC.EGeSOR was a randomized study of HNC patients aged ≥65, receiving a pretreatment GA, a geriatric intervention and follow-up (intervention) or standard of care (control). The primary endpoint was QoL score using the European Organisation for Research and Treatment of Cancer's (EORTC QLQ-C30) and HNC (QLQ-HN35) QoL questionnaires over 24 months.In total, 475 patients were included (median age: 75.3; women: 31%; oral cancer: 44%). QoL scores improved over 24 months with various trajectories, without significant differences between the groups. A total of 74% of patients (interventional group) did not receive the complete intervention. Cancer characteristics, functional status, and risk of frailty were associated with change in the Global Health Status QoL score.There is a need to develop an alternative model of implementation such as patient-centered health-care pathways. TRIAL REGISTRATION: NCT02025062.

Comparison of the prognostic value of eight nutrition-related tools in older patients with cancer: A prospective study.

OBJECTIVES: The primary objective of the present study was to evaluate and compare the ability of eight nutrition-related tools to predict 1-year mortality in older patients with cancer. DESIGN, SETTING AND PARTICIPANTS: We studied older patients with cancer from the ELCAPA cohort and who had been referred for a geriatric assessment at one of 14 participating geriatric oncology clinics in the greater Paris area of France between 2007 and 2018. MEASUREMENTS: The studied nutrition-related tools/markers were the body mass index (BMI), weight loss (WL) in the previous 6 months, the Mini Nutritional Assessment, the Geriatric Nutritional Risk Index (GNRI), the Prognostic Nutritional Index, the Glasgow Prognostic Score (GPS), the modified GPS, and the C-reactive protein/albumin ratio. RESULTS: A total of 1361 patients (median age: 81; males: 51%; metastatic cancer: 49%) were included in the analysis. Most of the tools showed a progressively increase in the mortality risk as the nutrition-related risk category worsened (overall p-values <0.02 for all) after adjustment for age, outpatient status, functional status, severe comorbidities, cognition, mood, cancer treatment strategy, tumour site, and tumour metastasis. All the models were discriminant, with a C-index ranging from 0.748 (for the BMI) to 0.762 (for the GPS). The concordance probability estimate ranged from 0.764 (WL) to 0.773 (GNRI and GPS)). CONCLUSION: After adjustment for relevant prognostic factors, all eight nutrition-related tools/markers were independently associated with 1-year mortality in older patients with cancer. Depending on the time or context of the GA, physicians do not always have the time or means to perform and assess all the tools/markers compared here. However, even when some information is missing, each nutritional tool/marker has prognostic value and can be used in the evaluation.

[Knowledge and application of the HAS recommendations concerning the diagnosis of undernutrition in people aged 70 and above: an international online survey among members of the "Société Française de Gériatrie et de Gérontologie"]. / Connaissances et application des recommandations HAS concernant le diagnostic de la dénutrition chez la personne de 70 ans et plus : une enquête menée en ligne auprès des membres de la Société française de gériatrie et de gérontologie.

OBJECTIVES: To assess the knowledge and the use in clinical practice of the "French National Authority for Health" (HAS) 2021 recommendations on the diagnosis of malnutrition in older adults aged 70 years and above. METHODS: An online survey was developed by the working Group on Geriatrics and Nutrition (GEGN) of the "Société Française de Gériatrie et de Gérontologie (SFGG)" and conducted among members of the SFGG. A self-administered questionnaire composed of 21 closed questions was used. RESULTS: A total of 132 (10.2 %) members of the SFGG responded to the survey. The respondents were aged 43.4 ± 9.94 years old and 97 (73.5 %) were women. Almost half of them were medical doctors (n = 53 ; 40.2 %). Of the respondents, 81 % had already heard of the HAS 2021 recommendations. This percentage is higher for doctors (96 %) than for other professions (74 %). French respondents were more likely to have heard of these -recommendations (84 %) than respondents from other countries (42.9 %). However, only 41.6 % of the respondents believe they know these recommendations in detail. On a visual analogue scale from 0 (never) to 100 (always), respondents use these recommendations in their professional practice at 76.8 ± 20.2 %. However, on a scale from 0 (never difficult) to 100 (always difficult), some barriers to their use in clinical practice were highlighted. These mainly concerned the measurement of muscle mass (84.4 ± 17.2 %) and muscle strength (79.5 ± 19.9 %) in patients. CONCLUSION: Although the majority of respondents use the HAS 2021 recommendations in their professional practice, they often have difficulties in measuring muscle strength and muscle mass of their patients. The assessment of sarcopenia still needs to be implemented in clinical routine. Until then, better communication about simple alternatives that do not require special equipment is needed.

Cancer mortality and competing causes of death in older adults with cancer: A prospective, multicentre cohort study (ELCAPA-19).

BACKGROUND: In older patients with cancer, comorbidities compete with cancer for cause of death. The objectives were to evaluate cancer mortality and factors associated, according to metastatic status. METHODS: Between 2007 and 2014, patients with cancer aged ≥70 referred for pre-therapeutic geriatric assessment (GA) were included through the ELCAPA prospective cohort study. The underlying cause of death was defined according to the International Classification of Diseases, 10th Revision. The World Health Organisation definition was used to categorise the cause of death as cancer versus another disease (e.g. cardiovascular disease, infectious disease, etc.) Competing risk models were used. RESULTS: Mean (SD) age of the 1445 included patients was 80.2 (5.8) and 48% were women. Most common tumour sites were colorectal (19%), breast (17%) and urinary (15%); 773 patients (49%) had metastases. After a 34-month median follow-up, 706 cancer deaths were observed among 843 deaths. The 6-month and 3-year cancer mortality rates (95% CI) were 12% (9-15) and 34% (29-38) for non-metastatic patients and 43% (39-47) and 79% (75-82) for metastatic patients, respectively. Dependency in activities of daily living and comorbidities were associated with 6-month and 3-year cancer mortality in non-metastatic (adjusted subhazard ratio [aSHR] = 1.68 [0.99-2.85] and 1.69 [1.16-2.45]; and 1.98 [1.08-3.63] and 3.38 [1.47-7.76], respectively) and metastatic patients (aSHR = 2.81 [2.01-3.93] and 2.95 [2.14-4.07]; and 1.63 [1.18-2.25] and 2.06 [1.39-3.05], respectively). Impaired Timed-Get-Up-and-Go test was associated with 6-month and 3-year cancer mortality in metastatic patients (aSHR = 1.5 [1.06-2.12] and 1.38 [1.06-1.81], respectively). Obesity was negatively associated with 3-year cancer death in non-metastatic (aSHR = 0.53 [0.29-0.97]) and metastatic patients (aSHR = 0.71 [0.51-1.00]). CONCLUSIONS: The majority of older adults with cancer referred for pre-therapeutic GA die from cancer. Geriatric parameters are independently associated with cancer mortality and should be considered for prognosis assessment, decision-making and care.

Impact of Cardiovascular Comorbidities on the Effectiveness and Safety of Bevacizumab in Older Patients with Metastatic Colorectal Cancer.

BACKGROUND: Cardiovascular comorbidities are not contraindications of bevacizumab for metastatic colorectal cancer. OBJECTIVE: We aimed to evaluate the impact of cardiovascular comorbidities before bevacizumab treatment on overall survival and cardiovascular safety in older patients with metastatic colorectal cancer. METHODS: A 2009-2015 cohort of patients with metastatic colorectal cancer aged ≥ 65 years administered first-line bevacizumab was extracted from the French healthcare reimbursement claims database. Baseline heart failure, hypertension, and venous/arterial thromboembolic events were identified. The 36-month overall survival rate was evaluated using the Kaplan-Meier method, and the impact of cardiovascular comorbidities on the 36-month overall survival using a time-dependent, multivariable, Cox proportional hazards model. The 36-month cumulative incidence of cardiovascular events, and the impact of cardiovascular comorbidities on the likelihood of cardiovascular events were evaluated using the Fine and Gray model, with death as a competing risk. RESULTS: We included 9222 patients (56.4% male; median age 73 years). Two-thirds (66.7%) had baseline cardiovascular comorbidities. The median 36-month overall survival was 20.4 [95% confidence interval (CI) 19.9-21.0] and 21.8 [95% CI 21.1-22.6] months in patients with and without cardiovascular comorbidities, respectively. Age ≥ 75 years, dependency in activities of daily living, radiotherapy, and another targeted therapy were identified as death risk factors, but not cardiovascular comorbidities. At 36 months, cardiovascular events had occurred in 60.2% [95% CI 58.9-61.4] and 44.1% [95% CI 42.3-45.9] of patients with and without cardiovascular comorbidities. Baseline venous thrombosis, female, three or more cardiovascular medications, another targeted therapy, and more than six bevacizumab injections were identified as risk factors for cardiovascular events. CONCLUSIONS: In clinical practice, cardiovascular comorbidities before administering bevacizumab to older patients with metastatic colorectal cancer impacted the cardiovascular safety, but not overall survival. Unless they limit functional independency, older patients with cardiovascular comorbidities should be treated with bevacizumab under close monitoring.

Predictors of three-month mortality and severe chemotherapy-related adverse events in patients aged 70 years and older with metastatic non-small-cell lung cancer: A secondary analysis of ESOGIA-GFPC-GECP 08-02 study.

INTRODUCTION: Predictors for mortality and toxicity in older patients with cancer are mainly studied in cohorts with various cancers at different stages. This study aims to identify predictive geriatric factors (PGFs) for early death and severe chemotherapy related adverse events (CRAEs) in patients aged ≥70 years with metastatic non-small-cell lung cancer (mNSCLC). MATERIAL AND METHODS: This is a secondary analysis of the multicenter, randomized, phase 3 ESOGIA trial that compared, for patients ≥70 years with mNSCLC, a treatment algorithm based on performance status and age to another algorithm based on geriatric assessment. To identify PGFs of three-month mortality and grade 3, 4, or 5 CRAEs, multivariate Cox models and logistic models, adjusted for treatment group and center, and stratified by randomization arm, were constructed. RESULTS: Among 494 included patients, 145 (29.4%) had died at three months and 344 (69.6%) had severe chemotherapy toxicity. For three-month mortality, multivariate analyses retained mobility (Test Get up and Go), instrumental activity of daily living (IADL) dependence and weight loss as PGFs. The combined effect of IADL ≤2/4 and weight loss ≥3 kg was strongly associated with three-month mortality (adjusted hazard ratio: 5.71 [95% confidence interval [CI]: 2.64-12.32]). For chemotherapy toxicity, Charlson Comorbidity Index ≥2 was independently associated with grade3, 4, or 5 CRAEs (adjusted odds ratio [95% CI]: 1.94 [1.06-3.56]). DISCUSSION: Mobility, IADL dependence, and weight loss were predictive of three-month mortality in a population aged ≥70 years treated for mNSCLC, while comorbidities were independently associated with severe chemotherapy toxicity.

External Validity of Two Scores for Predicting the Risk of Chemotherapy Toxicity Among Older Patients With Solid Tumors: Results From the ELCAPA Prospective Cohort.

BACKGROUND: Severe chemotherapy-related toxicities are frequent among older patients. The Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) and the Cancer and Aging Research Group Study (CARG) score were both developed to predict these events. PATIENTS AND METHODS: The objective of this study was to evaluate the scores' predictive performance in a prospective cohort, which included patients aged 70 years and older referred for a geriatric assessment prior to chemotherapy for a solid tumor. The main endpoints were grades 3/4/5 toxicities for the CARG score and grades 4/5 hematologic toxicities and grades 3/4/5 non-hematologic toxicities for the CRASH score. RESULTS: A total of 248 patients were included, of which 150 (61%) and 126 (51%) experienced at least one severe adverse event as defined respectively in CARG and CRASH studies. The incidence of adverse events was not significantly greater in the intermediate and high-risk CARG groups than in the low-risk group (odds ratio (OR) [95% CI] = 0.3 [0.1-1.4] (P = .1) and 0.4 [0.1-1.7], respectively). The area under curve (AUC) was 0.55. Similarly, the incidence of severe toxicities was no greater in the intermediate-low, intermediate-high, and high-risk CRASH groups than in the low-risk CRASH group (OR [95%CI] = 1 [0.3-3.6], 1 [0.3-3.4], and 1.5 [0.3-8.1], respectively). The AUC was 0.52. The type of cancer, performance status, comorbidities, body mass index, and MAX2 index were independently associated with grades 3/4/5 toxicities. CONCLUSION: In an external cohort of older patients referred for a pretherapeutic GA, the CARG and CRASH scores were poor predictors of the risk of chemotherapy severe toxicities.

Prevalence of Four Sarcopenia Criteria in Older Patients with Cancer, and Their Predictive Value for 6-Month Mortality: The NutriAgeCancer National Prospective Cohort Study.

Older cancer patients have an elevated risk of sarcopenia. The aim was to estimate the prevalence of four criteria for sarcopenia case finding, assessment, diagnosis, and severity determination: abnormal strength, assistance with walking, rising from a chair, climbing stairs, and falls (SARC-F), low hand-grip strength (HGS), low arm circumference (AC, a muscle mass proxy), and low physical performance (PP). Sarcopenia (low HGS and AC) and severe sarcopenia (low HGS, AC, and PP) and their predictive values for 6-month mortality were estimated in the whole population and by metastatic status. We analyzed data from the NutriAgeCancer French nationwide study of cancer patients aged ≥70 referred for geriatric assessment before anti-cancer treatment. We performed Cox proportional hazards analysis for each criterion separately and all criteria combined. Overall, 781 patients from 41 geriatric oncology clinics were included (mean age: 83.1; females: 53%; main cancer types: digestive (29%) and breast (17%); metastases: 42%). The prevalence of abnormal SARC-F, low HGS, a low AC, low PP, sarcopenia, and severe sarcopenia were, respectively, 35.5%, 44.6%, 44.7%, 35.2%, 24.5%, and 11.7%. An abnormal SARC-F and/or low HGS, sarcopenia, and severe sarcopenia were associated with 6-month mortality in patients with metastases (adjusted hazard ratios [95% confidence interval]: 2.72 [1.34-5.49], 3.16 [1.48-6.75] and 6.41 [2.5-16.5], respectively). Sarcopenia was strongly predictive of 6-month mortality in patients with metastatic cancer.

Pre-Therapeutic Sarcopenia among Cancer Patients: An Up-to-Date Meta-Analysis of Prevalence and Predictive Value during Cancer Treatment.

This study will address the prevalence of pre-therapeutic sarcopenia (PS) and its clinical impact during cancer treatment among adult cancer patients ≥ 18 years of age. A meta-analysis (MA) with random-effect models was performed via a MEDLINE systematic review, according to the PRISMA statement, focusing on articles published before February 2022 that reported observational studies and clinical trials on the prevalence of PS and the following outcomes: overall survival (OS), progression-free survival (PFS), post-operative complications (POC), toxicities (TOX), and nosocomial infections (NI). A total of 65,936 patients (mean age: 45.7-85 y) with various cancer sites and extensions and various treatment modes were included. Mainly defined by CT scan-based loss of muscle mass only, the pooled prevalence of PS was 38.0%. The pooled relative risks were 1.97, 1.76, 2.70, 1.47, and 1.76 for OS, PFS, POC, TOX, and NI, respectively (moderate-to-high heterogeneity, I2: 58-85%). Consensus-based algorithm definitions of sarcopenia, integrating low muscle mass and low levels of muscular strength and/or physical performance, lowered the prevalence (22%) and heterogeneity (I2 < 50%). They also increased the predictive values with RRs ranging from 2.31 (OS) to 3.52 (POC). PS among cancer patients is prevalent and strongly associated with poor outcomes during cancer treatment, especially when considering a consensus-based algorithm approach.

Safety and efficacy of immunotherapy according to the age threshold of 80 years.

BACKGROUND: To compare safety and efficacy of ICIs among patients<80 and those ≥80 years of age. METHODS: A single-center retrospective observational cohort study comparing patients<80 and ≥80 years of age matched for cancer site (lung vs others) and participation in a clinical trial. PRIMARY ENDPOINT: grade ≥2 toxicity during the first three months of ICI therapy. The two groups were compared using univariate and multivariate regression. RESULTS: Two hundred and ten consecutive patients were recruited, with the following characteristics: mean age: 66.5±16.8, 20% aged ≥80 years, 75% male, 97% ECOG-PS ≤ 2, 78% G8-index ≤ 14/17, 80% lung or kidney cancer, and 97% metastatic cancer. The grade ≥2 toxicity rate during the first three months of ICI therapy was 68%. Patients aged ≥80 years of age had a more significant (P<0.05) proportion of grade ≥2 non-hematological toxicities (64% vs 45%) than those aged<80 years: rash (14% vs 4%), arthralgia (7.1% vs 0.6%), colitis (4.7% vs 0.6%), cytolysis (7.1% vs 1.2%), gastrointestinal bleeding (2.4% vs 0%), onycholysis (2.4% vs 0%), oral mucositis (2.4% vs 0%), psoriasis (2.4% vs 0%), or other skin toxicities (25% vs 3%). Efficacy among patients ≥80 and<80 years of age was comparable. CONCLUSIONS: Although non-hematological toxicities affected 20% more patients aged ≥80 years, hematological toxicities and efficacy were comparable between patients aged ≥80 and<80 years with advanced cancer and treated with ICIs.

The 10-month mortality rate among older patients treated for digestive system cancer during the first wave of the COVID-19 pandemic: The CADIGCOVAGE multicentre cohort study.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has had a dramatic impact on cancer diagnosis and care pathways. Here, we assessed the mid-term impact of the COVID-19 pandemic on older adults with cancer before, during and after the lockdown period in 2020. MATERIALS AND METHODS: We performed a retrospective, observational, multicentre cohort study of prospectively collected electronic health records. All adults aged 65 or over and having been newly treated for a digestive system cancer in our institution between January 2018 until August 2020 were enrolled. RESULTS: Data on 7,881 patients were analyzed. Although the overall 10-month mortality rate was similar in 2020 vs. 2018-2019, the mortality rate among for patients newly treated in the 2020 post-lockdown period was (after four months of follow-up) significantly higher. A subgroup analysis revealed higher mortality rates for (i) patients diagnosed in the emergency department during the pre-lockdown period, (ii) patients with small intestine cancer newly treated during the post-lockdown period, and (iii) patients having undergone surgery with curative intent during the post-lockdown period. However, when considering individuals newly treated during the lockdown period, we observed lower mortality rates for (i) patients aged 80 and over, (ii) patients with a biliary or pancreatic cancer, and (iii) patients diagnosed in the emergency department. DISCUSSION: There was no overall increase in mortality among patients newly treated in 2020 vs. 2018-2019. Longer follow-up is needed to assess the consequences of the pandemic. A subgroup analysis revealed significant intergroup differences in mortality.

Should we screen for colorectal cancer in people aged 75 and over? A systematic review - collaborative work of the French geriatric oncology society (SOFOG) and the French federation of digestive oncology (FFCD).

BACKGROUND: We have done a systematic literature review about CRC Screening over 75 years old in order to update knowledge and make recommendations. METHODS: PUBMED database was searched in October 2021 for articles published on CRC screening in the elderly, and generated 249 articles. Further searches were made to find articles on the acceptability, efficacy, and harms of screening in this population, together with the state of international guidelines. RESULTS: Most benefit-risk data on CRC screening in the over 75 s derived from simulation studies. Most guidelines recommend stopping cancer screening at the age of 75. In private health systems, extension of screening up to 80-85 years is, based on the life expectancy and the history of screening. Screening remains effective in populations without comorbidity given their better life-expectancy. Serious adverse events of colonoscopy increase with age and can outweigh the benefit of screening. The great majority of reviews concluded that screening between 75 and 85 years must be decided case by case. CONCLUSION: The current literature does not allow Evidence-Based Medicine propositions for mass screening above 75 years old. As some subjects over 75 years may benefit from CRC screening, we discussed ways to introduce CRC screening in France in the 75-80 age group. IRB: An institutional review board composed of members of the 2 learned societies (SOFOG and FFCD) defined the issues of interest, followed the evolution of the work and reviewed and validated the report.

A Two-Step Frailty Assessment Strategy in Older Patients With Solid Tumors: A Decision Curve Analysis.

PURPOSE: The intended clinical value of frailty screening is to identify unfit patients needing geriatric assessment (GA) and to prevent unnecessary GA in fit patients. These hypotheses rely on the sensitivity and specificity of screening tests, but they have not been verified. METHODS: We performed a cross-sectional analysis of outpatients age ≥ 70 years with prostate, breast, colorectal, or lung cancer included in the ELCAPA cohort study (ClinicalTrials.gov identifier: NCT02884375) between February 2007 and December 2019. The diagnostic accuracy of the G8 Geriatric Screening Tool (G8) and modified G8 scores for identifying unfit patients was determined on the basis of GA results. We used decision curve analysis to calculate the benefit of frailty screening for detecting unfit patients and avoiding unnecessary GA in fit patients across different threshold probabilities. RESULTS: We included 1,648 patients (median age, 81 years), and 1,428 (87%) were unfit. The sensitivity and specificity were, respectively, 85% (95% CI, 84 to 87) and 59% (95% CI, 57 to 61) for G8, and 86% (95% CI, 84 to 87) and 60% (95% CI, 58 to 63) for the modified G8 score. For decision curve analysis, the net benefit (NB) for identifying unfit patients were 0.72 for G8, 0.72 for the modified G8, and 0.82 for GA at a threshold probability of 0.25. At a threshold probability of 0.33, the NBs were 0.71, 0.72, and 0.80, respectively. At a threshold probability of 0.5, the NBs were 0.68, 0.69, and 0.73, respectively. No screening tool reduced unnecessary GA in fit patients at predefined threshold probabilities. CONCLUSION: Although frailty screening tests showed good diagnostic accuracy, screening showed no clinical benefits over the GA-for-all strategy. NB approaches, in addition to diagnostic accuracy, are necessary to assess the clinical value of tests.

Advances in Geriatric Oncology: Exploring Practical Ways to Optimize Treatment in Older Patients with Cancer.

Cancer is a disease associated with aging, with patients over 70 accounting for 50% of newly diagnosed malignancies and 70% of all cancer deaths [...].

Effectiveness of Geriatric Assessment-Driven Interventions on Survival and Functional and Nutritional Status in Older Patients with Head and Neck Cancer: A Randomized Controlled Trial (EGeSOR).

This study assesses the efficacy of Geriatric Assessment (GA)-driven interventions and follow-up on six-month mortality, functional, and nutritional status in older patients with head and neck cancer (HNC). HNC patients aged 65 years or over were included between November 2013 and September 2018 by 15 Ear, Nose, and Throat (ENT) and maxillofacial surgery departments at 13 centers in France. The study was of an open-label, multicenter, randomized, controlled, and parallel-group design, with independent outcome assessments. The patients were randomized 1:1 to benefit from GA-driven interventions and follow-up versus standard of care. The interventions consisted in a pre-therapeutic GA, a standardized geriatric intervention, and follow-up, tailored to the cancer-treatment plan for 24 months. The primary outcome was a composite criterion including six-month mortality, functional impairment (fall in the Activities of Daily Living (ADL) score ≥2), and weight loss ≥10%. Among the patients included (n = 499), 475 were randomized to the experimental (n = 238) or control arm (n = 237). The median age was 75.3 years [70.4-81.9]; 69.5% were men, and the principal tumor site was oral cavity (43.9%). There were no statistically significant differences regarding the primary endpoint (n = 98 events; 41.0% in the experimental arm versus 90 (38.0%); p = 0.53), or for each criterion (i.e., death (31 (13%) versus 27 (11.4%); p = 0.48), weight loss of ≥10% (69 (29%) versus 65 (27.4%); p = 0.73) and fall in ADL score ≥2 (9 (3.8%) versus 13 (5.5%); p = 0.35)). In older patients with HNC, GA-driven interventions and follow-up failed to improve six-month overall survival, functional, and nutritional status.

The Prognostic Value of Eight Comorbidity Indices in Older Patients with Cancer: The ELCAPA Cohort Study.

Background: A prognostic assessment is crucial for making cancer treatment decisions in older patients. We assessed the prognostic performance (relative to one-year mortality) of eight comorbidity indices in a cohort of older patients with cancer. Methods: We studied patients with cancer aged ≥70 included in the Elderly Cancer Patient (ELCAPA) cohort between 2007 and 2010. We assessed seven nonspecific indices (Charlson Comorbidity Index (CCI), three modified versions of the CCI, the Elixhauser Comorbidity Index, the Gagne index, and the Cumulative Illness Rating Scale for Geriatrics (CIRS-G)) and the National Cancer Institute Comorbidity Index. Results: Overall, 510 patients were included. Among patients with nonmetastatic cancer, all the comorbidity indices were independently associated with 1-year mortality (adjusted hazard ratios (aHRs) of 1.44 to 2.51 for one standard deviation increment; p < 0.05 for all) and had very good discriminant ability (Harrell's C > 0.8 for the eight indices), but were poorly calibrated. Among patients with metastatic cancer, only the CIRS-G was independently associated with 1-year mortality (aHR (95% confidence interval): 1.26 [1.06−1.50]). Discriminant ability was moderate (0.61 to 0.70) for the subsets of patients with metastatic cancer and colorectal cancer. Conclusion: Comorbidity indices had strong prognostic value and discriminative ability for one-year mortality in older patients with nonmetastatic cancer, although calibration was poor. In older patients with metastatic cancer, only the CIRS-G was predictive of one-year mortality.

Geriatric impairments were directly and indirectly associated with mortality in older patients with cancer: a structural equation analysis.

OBJECTIVES: We assessed the direct and indirect effects between six geriatric domains and 6- and 12-month mortality in older cancer patients. STUDY DESIGN AND SETTING: We included cancer patients aged ≥70 years from the Elderly Cancer Patients cohort, referred for geriatric assessment between 2007 and 2016. We used structural equation modelling to examine the interrelationships between six geriatric domains (function and mobility, nutrition, cognition, mood, comorbidities and polypharmacy, and social support) and the direct and indirect relationships between these domains, the cancer stage, site, and treatment on the one hand and mortality on the other. RESULTS: The analysis included 1,434 patients (mean age: 80 ± 5.6 years; women: 48%; main cancer sites: digestive tract [36.2%], urinary tract and prostate [26.6%], and breast [16.5%]; metastatic cancer: 48%). Direct relationships to 6- and 12-month mortality were identified for functional impairment (standardized coefficient [SC]: 0.37 [P < 0.001] and 0.32 [P < 0.001], respectively), poor nutritional status (SC: 0.11 [P = 0.005] and 0.14 [P = 0.001]), poor social support (SC = 0.07 [P = 0.08] and 0.09 [P = 0.02]), cancer site, stage, and treatment. The effects of comorbidities, cognitive impairment, and depression on mortality were mediated by functional and nutritional status. CONCLUSION: In older cancer patients, functional and nutritional impairments were the strongest direct prognostic geriatric factors for mortality.