Association of cancer with functional decline at old age: a longitudinal study in Danish twins.

INTRODUCTION: There is evidence that older adults with cancer have a higher risk of functional decline than cancer-free older adults. However, few studies are longitudinal, and none are twin studies. Thus, we aimed to investigate the relationship between cancer and functional decline in older adult (aged 70+ years) twins. MATERIALS AND METHODS: Cancer cases in the Longitudinal Study of Aging Danish Twins were identified through the Danish Cancer Registry. Functional status was assessed using hand grip strength (6 years follow-up), and self-reported questions on mobility (10 years follow-up), and cut-offs were defined to assess functional decline. Cox regression models were performed for all the individual twins. In addition, we extended the analysis to discordant twin pairs (twin pairs with one having cancer and the other being cancer-free), to control to a certain extent for (unmeasured) shared confounders (genetic and environmental factors). RESULTS: The analysis based on individual twins showed that individual twins with cancer are at increased hazard of worsening hand grip strength (hazard ratio (HR) 1.37, 95% confidence interval (CI) 1.04, 1.80) than cancer-free twins. Among the discordant twin pairs, twins with cancer had a higher hazard of worsening hand grip strength (HR 3.50, 95% CI 1.15, 10.63) than cancer-free cotwins. In contrast, there was no evidence of a difference between the hazard of experiencing mobility decline for twins with cancer compared with cancer-free twins, in both individual twins and discordant twin pairs analyses. DISCUSSION: Cancer was associated with hand grip strength functional decline in old individual twins and discordant pairs. Our results strengthen the importance of comprehensive geriatric assessment in older adults with cancer, as well as the importance of routine assessment of functional status. Promoting physical activity through exercise training programmes could enable the prevention of functional decline in older adults with cancer.

Hospital-based palliative care referrals: determinants in older adults with cancer.

OBJECTIVES: Early palliative care improves the quality of life of older patients with cancer. This work aimed to analyse the effect of sociodemographic, geriatric, and tumour-related determinants on hospital-based palliative care (HPC) referral in older patients with cancer, taking into account competing risk of death. METHODS: Older adults with diagnosed cancer from 2014 to 2018 according to the general cancer registry of Gironde (French department) were identified in three population-based cohorts on ageing (PAQUID, 3C - Three City, AMI). Cause-specific Cox models focused on 10 usual determinants in geriatric oncology and palliative care: age, gender, living alone, place of residency, tumour prognosis, activities of daily living (ADL) and instrumental-ADL (IADL) limitations, cognitive impairment, depressive disorders, and polypharmacy. RESULTS: 131 patients with incident cancer (mean age: 86.2 years, men: 62.6%, poor cancer prognosis: 32.8%) were included, HPC occurring for 26 of them. Unfavourable cancer prognosis was a key determinant for HPC referral (HR 7.02, 95% CI 2.86 to 17.23). An altered IADL score was associated with precocious (first year) referral (HR 3.21, 95% CI 1.20 to 8.64, respectively). Women had a higher rate immediately (first week) after diagnosis (HR 8.64, 95% CI 1.27 to 87.27). CONCLUSIONS: Cancer prognosis, functional decline and gender are independent factors of HPC referral in older patients with cancer. These findings may help for a better anticipation of the healthcare pathway.

Assessing patient-reported outcomes (PROs) and patient-related outcomes in randomized cancer clinical trials for older adults: Results of DATECAN-ELDERLY initiative.

As older adults with cancer are underrepresented in randomized clinical trials (RCT), there is limited evidence on which to rely for treatment decisions for this population. Commonly used RCT endpoints for the assessment of treatment efficacy are more often tumor-centered (e.g., progression-free survival). These endpoints may not be as relevant for the older patients who present more often with comorbidities, non-cancer-related deaths, and treatment toxicity. Moreover, their expectation and preferences are likely to differ from younger adults. The DATECAN-ELDERLY initiative combines a broad expertise, in geriatric oncology and clinical research, with interest in cancer RCT that include older patients with cancer. In order to guide researchers and clinicians coordinating cancer RCT involving older patients with cancer, the experts reviewed the literature on relevant domains to assess using patient-reported outcomes (PRO) and patient-related outcomes, as well as available tools related to these domains. Domains considered relevant by the panel of experts when assessing treatment efficacy in RCT for older patients with cancer included functional autonomy, cognition, depression and nutrition. These were based on published guidelines from international societies and from regulatory authorities as well as minimum datasets recommended to collect in RCT including older adults with cancer. In addition, health-related quality of life, patients' symptoms, and satisfaction were also considered by the panel. With regards to tools for the assessment of these domains, we highlighted that each tool has its own strengths and limitations, and very few had been validated in older adults with cancer. Further studies are thus needed to validate these tools in this specific population and define the minimum clinically important difference to use when developing RCTs in this population. The selection of the most relevant tool should thus be guided by the RCT research question, together with the specific properties of the tool.

First-line real-world treatment patterns and survival outcomes in women younger or older than 40 years with metastatic breast cancer in the real-life multicenter French ESME cohort.

AIM: To describe first-line treatment patterns, overall survival (OS) and real-world progression-free survival (rwPFS) in young women (<40) with metastatic breast cancer (mBC), as compared to women aged 40-69. MATERIALS AND METHODS: Data on adult women diagnosed with mBC (2008-2017) were extracted from the ESME mBC database (NCT03275311) which includes consecutive patients starting first-line metastatic treatment in one of the 18 French Comprehensive cancer centers. We reported first-line therapeutic strategy and prognostic factors of OS and rwPFS for women aged < 40 and 40-69. RESULTS: In total, 14,897 mBC women were included (1512 aged <40). HR+ /HER2- mBC was the most frequent subtype. First-line treatment differed between young patients and older ones for HR+ /HER2- and Triple Negative (TN) mBC. Median OS for women aged < 40 and 40-69, respectively, was 46.9 and 46.2 months for HR+ /HER2- mBC; 13.5 and 15.2 for TN mBC; and, 60.7 and 55.1 for HER2 + mBC. Median rwPFS under first line treatment was 11.6 and 11.9 months for HR+ /HER2- in women aged < 40 and 40-69, respectively; 5.5 and 5.9 for TN, and, 13.3 and 12.9 for HER2 + . Factors associated with shorter OS and rwPFS were similar for both women aged < 40 and 40-69 and included ≥ 3 metastatic sites, visceral metastases, and longer MFI, with time-varying effects observed for several prognostic factors. CONCLUSION: Young women presented more frequently with TN and HER2 + subtypes and aggressive mBC than women aged 40-69 did. Prognostic factors of OS and rwPFS were quite similar between age groups and mBC subtypes.

Association between pre-diagnosis geriatric syndromes and overall survival in older adults with cancer (the INCAPAC study).

INTRODUCTION: Several population-based studies have reported disparities in overall survival (OS) among older patients with cancer. However, geriatric syndromes, known to be associated with OS in the geriatric population, were rarely studied. Thus, our aim was to identify the determinants of OS among French older adults with cancer, including geriatric syndromes before cancer diagnosis. MATERIALS AND METHODS: Using cancer registries, we identified older subjects (≥65 years) with cancer in three French prospective cohort studies on aging from the Gironde department. Survival time was calculated from the date of diagnosis to the date of all-cause death or to the date of last follow-up, whichever came first. Demographic and socioeconomic characteristics, smoking status, self-rated health, cancer-related factors (stage at diagnosis, treatment), as well as geriatric syndromes (polypharmacy, activity limitation, depressive symptomatology, and cognitive impairment or dementia) were studied. Analyses were performed using Cox proportional hazard models for the whole population, then by age group (65-84 and 85+). RESULTS: Among the 607 subjects included in the study, the median age at cancer diagnosis was 84 years. Smoking habits, activity limitations, cognitive impairment or dementia, advanced cancer stage and absence of treatment were significantly associated with lower OS in the analysis including the whole population. Women presented higher OS. Factors associated with OS differed by age group. Polypharmacy was inversely associated with OS in older adults aged 65-84 and 85 + . DISCUSSION: Our findings support that geriatric assessment is needed to identify patients at higher risk of death and that an evaluation of activity limitation in older adults is essential. Improving early detection could enable interventions to address factors (activity limitations, cognitive impairment) associated with OS, potentially reducing disparities and lead to earlier palliative care.

[Rethinking the management of elderly cancer patients : Proposals from the Age Cancer Priorities French Group]. / Repenser la prise en charge des sujets âgés atteints d'un cancer : propositions du groupe Priorités Âge Cancer.

The growing incidence of cancer associated with an aging population implies important health challenges that require questioning on the care management of older adults with cancer. There is a need to rethink the care management of older cancer patients with patient-centered decisions and an adjustment of the care pathway for this population. The Priorities Age Cancer (PAC) French group, made up of physicians, pharmacists and researchers in geriatric oncology, set up proposals to answer this need. First, the heterogeneity and the specificities of older adults as well as their preferences regarding cancer treatment goals, care management decisions must be patient-centered. The frailty screening tools should be generalized in clinical practice to provide geriatric assessment-guided recommendations and help for treatment decisions, and patients' involvement and shared decision should be developed. Second, older adults with cancer confront a complex health care system that demands a high level of health literacy. The caregivers, playing an essential role, may not be prepared for all these challenges. Thus, there is a need to promote health literacy by patient education, and patient-experts should be involved in health pathway. Third, there is a need to deal with dedicated partners and adjust the care pathway. New pathway careers as case-management nurses and specialized pharmacists should be involved in patient care and may play a central role together with other careers. Community-Hospital coordination should also be reinforced.

Overall and net survival of patients with sarcoma between 2005 and 2010: Results from the French Network of Cancer Registries (FRANCIM).

BACKGROUND: Sarcomas are rare, heterogeneous, ubiquitously localized malignancies with many histologic subtypes and genomic patterns. The survival of patients with sarcoma has rarely been described based on this heterogeneity; therefore, the authors' objective was to estimate survival outcomes in patients who had sarcomas using the 2020 version of the World Health Organization classification of soft tissue and bone tumors. METHODS: Patients older than 15 years who had incident sarcoma diagnosed between 2005 and 2010 were extracted from 14 French population-based cancer registries covering 18% of the French metropolitan population. Vital status for each patient was actively followed up to June 30, 2013. Net survival (NS) was estimated using the unbiased Pohar-Perme method. RESULTS: Overall, 4202 patients were included. NS declined with increasing age at diagnosis. According to topographic groups, large 5-year NS disparities were observed, ranging from 47% among women with gynecologic sarcomas to 89% among patients with skin sarcomas. Patients with soft tissue, bone, and gastrointestinal sarcomas had 5-year NS rates of 53%, 61%, and 70%, respectively. Similar heterogeneity was observed according to histologic subtypes, with 5-year NS ranging from 19% for patients with angiosarcomas to 96% for patients with dermatofibrosarcomas. Patients with sarcoma who displayed missense mutations had a better 5-year NS (74%); those with MDM2-amplified sarcomas had the worst NS (45%). CONCLUSIONS: NS rates in patients with sarcoma are presented here for the first time based on the 2020 World Health Organization classification applied to population-based registry data. Large prognostic heterogeneity was observed based on age, topographic and histologic groups, and genomic alteration profiles, constituting a benchmark for future studies and clinical trials.

Palliative care referral in cancer patients with regard to initial cancer prognosis: a population-based study.

OBJECTIVES: More than half of cancer patients require palliative care; however, inequality in access and late referral in the illness trajectory are major issues. This study assessed the cumulative incidence of first hospital-based palliative care (HPC) referral, as well as the influence of patient-, tumor-, and care-related factors. STUDY DESIGN: This is a retrospective population-based study. METHODS: The study included patients from the 2014 population-based cancer registry of Gironde, France. International Classification of Diseases, Tenth Revision, coding for palliative care identified HPC referrals from 2014 to 2018. The study included 8424 patients. Analyses considered the competing risk of death and were stratified by initial cancer prognosis (favorable vs unfavorable [if metastatic or progressive cancer]). RESULTS: The 4-year incidence of HPC was 16.7% (95% confidence interval, 16.6-16.8). Lung cancer led to more referrals, whereas breast, colorectal, and prostatic locations were associated to less frequent HPC compared with other solid tumors. Favorable prognosis central nervous system tumors and unfavorable prognosis hematological malignancies also showed less HPC. The incidence of HPC was higher in tertiary centers, particularly for older patients. In the favorable prognosis subgroup, older and non-deprived patients received more HPC. In the unfavorable prognosis subgroup, the incidence of HPC was lower in patients who lived in rural areas than those who lived in urban areas. CONCLUSIONS: One-sixth of cancer patients require HPC. Some factors influencing referral depend on the initial cancer prognosis. Our findings support actions to improve accessibility, especially for deprived patients, people living in rural areas, those with hematological malignancies, and those treated outside tertiary centers. In addition, consideration of age as factor of HPC may allow for improved design of the referral system.

Palliative versus hospice care in patients with cancer: a systematic review.

BACKGROUND: Guidelines recommend an early access to specialised palliative medicine services for patients with cancer, but studies have reported a continued underuse. Palliative care facilities deliver early care, alongside antineoplastic treatments, whereas hospice care structures intervene lately, when cancer-modifying treatments stop. AIM: This review identified factors associated with early and late interventions of specialised services, by considering the type of structures studied (palliative vs hospice care). DESIGN: We performed a systematic review, prospectively registered on PROSPERO (ID: CRD42018110063). DATA SOURCES: We searched Medline and Scopus databases for population-based studies. Two independent reviewers extracted the data and assessed the study quality using Joanna Briggs Institute critical appraisal checklists. RESULTS: The 51 included articles performed 67 analyses. Most were based on retrospective cohorts and US populations. The median quality scores were 19/22 for cohorts and 15/16 for cross-sectional studies. Most analyses focused on hospice care (n=37). Older patients, men, people with haematological cancer or treated in small centres had less specialised interventions. Palliative and hospice facilities addressed different populations. Older patients received less palliative care but more hospice care. Patients with high-stage tumours had more palliative care while women and patients with a low comorbidity burden received more hospice care. CONCLUSION: Main disparities concerned older patients, men and people with haematological cancer. We highlighted the challenges of early interventions for older patients and of late deliveries for men and highly comorbid patients. Additional data on non-American populations, outpatients and factors related to quality of life and socioeconomic status are needed.

Palliative care delivery according to age in 12,000 women with metastatic breast cancer: Analysis in the multicentre ESME-MBC cohort 2008-2016.

INTRODUCTION: Patients with metastatic breast cancer (MBC) often require inpatient palliative care (IPC). However, mounting evidence suggests age-related disparities in palliative care delivery. This study aimed to assess the cumulative incidence function (CIF) of IPC delivery, as well as the influence of age. METHODS: The national ESME (Epidemio-Strategy-Medical-Economical)-MBC cohort includes consecutive MBC patients treated in 18 French Comprehensive Cancer Centres. ICD-10 palliative care coding was used for IPC identification. RESULTS: Our analysis included 12,375 patients, 5093 (41.2%) of whom were aged 65 or over. The median follow-up was 41.5 months (95% confidence interval [CI], 40.5-42.5). The CIF of IPC was 10.3% (95% CI, 10.2-10.4) and 24.8% (95% CI, 24.7-24.8) at 2 and 8 years, respectively. At 2 years, among triple-negative patients, young patients (<65 yo) had a higher CIF of IPC than older patients after adjusting for cancer characteristics, centre and period (65+/<65: ß = -0.05; 95% CI, -0.08 to -0.01). Among other tumour sub-types, older patients received short-term IPC more frequently than young patients (65+/<65: ß = 0.02; 95% CI, 0.01 to 0.03). At 8 years, outside large centres, IPC was delivered less frequently to older patients adjusted to cancer characteristics and period (65+/<65: ß = -0.03; 95% CI, -0.06 to -0.01). CONCLUSION: We found a relatively low CIF of IPC and that age influenced IPC delivery. Young triple-negative and older non-triple-negative patients needed more short-term IPCs. Older patients diagnosed outside large centres received less long-term IPC. These findings highlight the need for a wider implementation of IPC facilities and for more age-specific interventions.

Determinants of functional decline in older adults experiencing cancer (the INCAPAC study).

BACKGROUND: Previous studies have reported on the higher risk of functional decline among older patients with cancer. However, few have focused on factors of functional decline in older persons with cancer and are mainly hospital-based and focus on consequences of cancer treatment. The aim of the study was to identify determinants of functional decline in older subjects with cancer in a population-based study. METHODS: Using cancer registries, we identified older subjects (age ≥ 65 years) with cancer in three prospective cohort studies from Gironde, a French department. Functional status was measured using the Instrumental Activities of Daily Living (IADL) and the basic Activities of Daily Living (ADL) scales, and functional decline was measured between cancer pre- and post-diagnosis visits. Studied variables were demographic and socioeconomic (age at diagnosis, sex, living alone, education), cancer-related (stage at diagnosis, treatment received), smoking status, health-related (polypharmacy, depressive symptomatology), and geriatric-specific (cognitive impairment or dementia). Analyses were performed using logistic regression models. RESULTS: Age (≥85 years), cognitive impairment or dementia, and advanced stage at diagnosis were associated with a higher risk of ADL limitations, whether considering death or not. Age (≥85 years), education and polypharmacy were associated with a higher risk of ADL and/or IADL limitations. CONCLUSIONS: We identified factors that could impact on ADL and/or IADL limitations in older patients with cancer. The information on these determinants is useful in clinical settings to identify patients with cancer at high risk of functional decline.

Determinants of cancer treatment and mortality in older cancer patients using a multi-state model: Results from a population-based study (the INCAPAC study).

INTRODUCTION: Several studies have reported disparities in the care management and survival of older cancer patients. The aim of our study was to identify determinants of treatment administration in this population of cancer patients aged over 65 years taking into account competing risks of death. METHODS: The INCAPAC study is a population-based study. Four cancer registries and three prospective cohort studies on older subjects (age ≥65 years) from Gironde, a French department, were merged to identify older cancer patients. We used a non-parametric multi-state model including three states (cancer, treatment and all-cause death). This model allowed studying determinants of treatment administration (all treatments including curative, symptomatic and palliative treatments) and mortality considering that patients can move from cancer state to death state, either directly or through the treatment phase. Studied variables were demographic and socioeconomic-, cancer-, health-, and geriatric-related. RESULTS: A total of 450 patients were included in the analyses. They were mainly aged 85 and over, men and educated. Among included patients, 372 (83%) received cancer treatment. In the final multivariate model, dementia was associated with a lower likelihood of receiving cancer treatment (HR = 0.68, 95% CI = 0.47-0.99). In treated patients, age, sex, comorbidities, dependency and stage at diagnosis were associated to all-cause mortality, and in untreated patients, diagnosis of dementia and stage at diagnosis were associated to mortality. CONCLUSION: Further studies are necessary to understand the impact of geriatric impairments on treatment administration and to develop clinical practice guidelines.

Sociodemographic, socioeconomic, and clinical determinants of survival in patients with cancer: A systematic review of the literature focused on the elderly.

Studies on cancer survival have revealed disparities not only between the elderly and their younger counterparts, but also among the elderly themselves. The aim of this work was to identify sociodemographic, socioeconomic, clinical, and care-related determinants of survival or mortality in older patients with cancer by a systematic synthesis of the literature. Understanding these factors is of great value for guiding health policies and programs aimed at reducing cancer survival disparities. We conducted a search of MEDLINE and SCOPUS databases under PRISMA guidelines. Results were limited to articles published in English and French from 2005 to 2015, and focused on elderly patients with cancer. The article selection was performed in a stepwise fashion: title, abstract, and full-text selection. Studied determinants and results of each article were synthesized. Forty-five articles were eligible and included in the study. We observed different ways of measuring socioeconomic status, comorbidities, and treatment among studies. Cancer-specific and overall survival were the main studied outcomes. Advanced age, low income, low socioeconomic status, presence of comorbidities, advanced stage, and poor tumor grade were found to be associated with lower survival or higher mortality. On the other hand, female gender and being married were predictive of increased survival or lower mortality. The next logical step is to carry out studies on elderly patients from different countries and to incorporate pertinent factors in a unique model. Moreover, specific geriatric health impairments should be taken into account in further research because of their association with survival.

Role of geriatric intervention in the treatment of older patients with cancer: rationale and design of a phase III multicenter trial.

BACKGROUND: In the general geriatric population, programs linking geriatric evaluation with interventions are effective for improving functional status and survival of the patients. Whether or not these interventions improve health related quality of life (HRQoL) or overall survival (OS) in older patients with cancer is not yet clear. Indeed, randomized data on the effect of such interventions on survival and HRQoL are rare and conflicting. We describe the rationale and design of a phase III multicenter trial aimed at assessing the efficacy of geriatric intervention in the management of elderly patients with cancer. METHODS/DESIGN: Approximately 1200 patients, 70 years and older, considered in need of a geriatric intervention based on the G8 screening tool will be randomized into two intervention arms. The 'Usual-care' arm involves standard oncological care based on pre-defined oncological protocols. In addition to the standard oncological care, the 'Case-management' arm involves a multidimensional geriatric assessment and interventions tailored for the patient. Efficacy will be assessed using a co-primary endpoint encompassing OS and HRQoL. DISCUSSION: This trial has been designed to assess whether focused geriatric case management can either improve OS or HRQoL in elderly cancer patients considered in need of geriatric assessment. TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT02704832 .