Implementing geriatric assessment and management for older Canadians with cancer: Adherence to and satisfaction with the intervention, results of the 5C study.

INTRODUCTION: Geriatric assessment and management (GAM) is recommended by professional organizations and recently several randomized controlled trials (RCTs) demonstrated benefits in multiple health outcomes. GAM typically leads to one or more recommendations for the older adult on how to optimize their health. However, little is known about how well recommendations are adhered to. Understanding these issues is vital to designing GAM trials and clinical programs. Therefore, the aim of this study was to examine the number of GAM recommendations made and adherence to and satisfaction with the intervention in a multicentre RCT of GAM for older adults with cancer. MATERIALS AND METHODS: The 5C study was a two-group parallel RCT conducted in eight hospitals across Canada. Each centre kept a detailed recruitment and retention log. The intervention teams documented adherence to their recommendations. Medical records were also reviewed to assess which recommendations were adhered to. Twenty-three semi-structured interviews were conducted with 12 members of the intervention teams and 11 oncology team members to assess implementation of the study and the intervention. RESULTS: Of the 350 participants who were enrolled, 173 were randomized to the intervention arm. Median number of recommendations was seven. Mean adherence to recommendations based on the GAM was 69%, but it varied by type of recommendation, ranging from 98% for laboratory tests to 28% for psychosocial/psychiatry oncology referrals. There was no difference in the number of recommendations or non-adherence to recommendations by sex, level of frailty, or functional status. Oncologists and intervention team members were satisfied with the study implementation and intervention delivery. DISCUSSION: Adherence to recommendations was variable. Adherence to laboratory investigations and further imaging were generally high but much lower for recommendations regarding psychosocial support. Further collaborative work with older adults with cancer is needed to understand how to optimize the intervention to be consistent with patient goals, priorities, and values to ensure maximal impact on health outcomes.

Impact of Geriatric Assessment and Management on Quality of Life, Unplanned Hospitalizations, Toxicity, and Survival for Older Adults With Cancer: The Randomized 5C Trial.

PURPOSE: American Society of Clinical Oncology recommends that older adults with cancer being considered for chemotherapy receive geriatric assessment (GA) and management (GAM), but few randomized controlled trials have examined its impact on quality of life (QOL). PATIENTS AND METHODS: The 5C study was a two-group parallel 1:1 single-blind multicenter randomized controlled trial of GAM for 6 months versus usual oncologic care. Eligible patients were age 70+ years, diagnosed with a solid tumor, lymphoma, or myeloma, referred for first-/second-line chemotherapy or immunotherapy or targeted therapy, and had an Eastern Cooperative Oncology Group performance status of 0-2. The primary outcome QOL was measured with the global health scale of the European Organisation for the Research and Treatment of Cancer QOL questionnaire and analyzed with a pattern mixture model using an intent-to-treat approach (at 6 and 12 months). Secondary outcomes included functional status, grade 3-5 treatment toxicity; health care use; satisfaction; cancer treatment plan modification; and overall survival. RESULTS: From March 2018 to March 2020, 350 participants were enrolled. Mean age was 76 years and 40.3% were female. Fifty-four percent started treatment with palliative intent. Eighty-one (23.1%) patients died. GAM did not improve QOL (global QOL of 4.4 points [95% CI, 0.9 to 8.0] favoring the control arm). There was also no difference in survival, change in treatment plan, unplanned hospitalization/emergency department visits, and treatment toxicity between groups. CONCLUSION: GAM did not improve QOL. Most intervention group participants received GA on or after treatment initiation per patient request. Considering recent completed trials, GA may have benefit if completed before treatment selection. The COVID-19 pandemic may have affected our QOL outcome and intervention delivery for some participants.

Efficacy of immune checkpoint inhibitors in older patients with non-small cell lung cancer: Real-world data from multicentric cohorts in Canada and France.

BACKGROUND: Age-related immune remodelling is thought to be associated with resistance to immune checkpoint inhibitors (ICIs) in cancer. Patients older than 70 years, representing >50% of the population with non-small cell lung cancer (NSCLC) according to SEER database, are underrepresented in clinical trials exploring ICIs. The objective of this study was to determine if patients with NSCLC older than ≥70 years had inferior clinical outcomes with ICIs. METHODS: We conducted a retrospective analysis of 381 patients treated with anti-PD-(L)1 ICI for advanced NSCLC at the Dijon Cancer Center (n = 177), University of Montreal Hospital (n = 106) and Quebec Heart and Lung Institute (n = 98). Age was considered as a categorical variable. Patients' baseline characteristics were compared using the Chi-squared test. Survival curves were estimated by the Kaplan-Meier method and compared with the Log-rank test in a univariate analysis. Multivariate cox regression model was used to determine hazard ratios and 95% confidence intervals for progression-free survival (PFS) and overall survival (OS) between the groups, adjusting for other clinicopathologic features. RESULTS: Among 381 patients included, 335 (88%) received ICI after platinum chemotherapy. The median age was 66 (range 37-89) and 33% were older than 70 years of age. Considering age as a categorical variable, differences in age were not associated with PFS or OS. Subgroup analysis and multivariate cox regression did not reveal significant interaction of age with outcomes. ECOG performance status was the only significant factor in the three cohorts. CONCLUSIONS: Unlike previously described in the era of chemotherapy, age was not associated with outcomes in NSCLC patients treated with ICI.

Clinical and Cost-effectiveness of a Comprehensive geriatric assessment and management for Canadian elders with Cancer-the 5C study: a study protocol for a randomised controlled phase III trial.

INTRODUCTION: Geriatric assessment and management is recommended for older adults with cancer referred for chemotherapy but no randomised controlled trial has been completed of this intervention in the oncology setting. TRIAL DESIGN: A two-group parallel single blind multi-centre randomised trial with a companion trial-based economic evaluation from both payer and societal perspectives with process evaluation. PARTICIPANTS: A total of 350 participants aged 70+, diagnosed with a solid tumour, lymphoma or myeloma, referred for first/second line chemotherapy, who speak English/French, have an Eastern Collaborative Oncology Group Performance Status 0-2 will be recruited. All participants will be followed for 12 months. INTERVENTION: Geriatric assessment and management for 6 months. The control group will receive usual oncologic care. All participants will receive a monthly healthy ageing booklet for 6 months. OBJECTIVE: To study the clinical and cost-effectiveness of geriatric assessment and management in optimising outcomes compared with usual oncology care. RANDOMISATION: Participants will be allocated to one of the two arms in a 1:1 ratio. The randomisation will be stratified by centre and treatment intent (palliative vs other). OUTCOME: Quality of life. SECONDARY OUTCOMES: (1) Cost-effectiveness, (2) functional status, (3) number of geriatric issues successfully addressed, (4) grades3-5 treatment toxicity, (5) healthcare use, (6) satisfaction, (7) cancer treatment plan modification and (8) overall survival. PLANNED ANALYSIS: For the primary outcome we will use a pattern mixture model using an intent-to-treat approach (at 3, 6 and12 months). We will conduct a cost-utility analysis alongside this clinical trial. For secondary outcomes 2-4, we will use a variety of methods. ETHICS AND DISSEMINATION: Our study has been approved by all required REBs. We will disseminate our findings to stakeholders locally, nationally and internationally and by publishing the findings. TRIAL REGISTRATION NUMBER: NCT03154671.

Health status, emergency department visits, and oncologists' feedback: An analysis of secondary endpoints from a randomized phase II geriatric assessment trial.

PURPOSE: Geriatric Assessment (GA) can help uncover previously unknown health issues and recommend tailored interventions to optimize outcomes; however, no completed randomized trial has examined the impact of GA on utility-based health status, healthcare use, and oncologists' opinions about GA. We examined these secondary outcomes of a randomized phase II trial. METHODS: A planned analysis of secondary outcomes of a two-group parallel single-blind randomized phase II trial of GA (ClinicalTrials.gov Identifier:NCT02222259) recruited patients ≥ age 70, diagnosed with stage II-IV breast/gastrointestinal/genitourinary cancer within six weeks of beginning chemotherapy at the Princess Margaret Cancer Centre, Toronto, Canada. Descriptive analyses using intent-to-treat were conducted for health status (EuroQol EQ-5D-3L) and healthcare utilization (patient self-report). Oncologist opinions were captured via open-ended interviews and summarized. RESULTS: A total of 95 patients who met the inclusion criteria were approached; 61 of them consented (64%). For health status, at all time-points, there were no significant differences between the two groups. The number of emergency department and family physician visits was low overall; there were no statistically significant differences between the two groups at any time point. All interviewed oncologists (eight of fourteen invited) were satisfied with the intervention, but wanted more straightforward recommendations and earlier GA results. CONCLUSIONS: No difference was found in terms of relationships between GA and utility-based health status or GA and healthcare use. Underreporting of healthcare use was possible. Oncologists welcome GA feedback and prefer to receive it in pre-treatment decision context. Larger trials with earlier GA are warranted.

A randomized phase II trial of geriatric assessment and management for older cancer patients.

PURPOSE: Geriatric assessment and management (GAM) can identify current health issues and recommend interventions to optimize well-being of older adults, but no randomized trial has yet been completed in oncology. Therefore, a randomized phase 2 trial was conducted. METHODS: A two-group parallel single-blinded randomized phase II trial ( ClinicalTrials.gov Identifier: NCT02222259) enrolled patients aged ≥70 years, diagnosed with stage 2-4 gastrointestinal, genitourinary, or breast cancer within 6 weeks of commencing chemotherapy at Princess Margaret Cancer Centre. The coprimary feasibility outcomes were the proportion of eligible patients enrolled and retained. The coprimary clinical outcomes were quality of life (QOL) (EORTC QLQ C30) and modification of cancer treatment. Descriptive and regression analyses using intent-to-treat analysis were conducted. RESULTS: Sixty-one persons (64%) agreed to participate (31 allocated to intervention arm and 30 to control group). In the control group, more participants died and refused follow-up. The benefit of intervention over control on QOL at 3 months was greater for those who survived 6 months (difference 9.28; 95% CI -10.35 to 28.91) versus those who survived only 3 months (difference 6.55; 95% CI -9.63 to 22.73). CONCLUSIONS: This trial showed that it was feasible to recruit and retain older adults for a GAM study. Those who survived at least 6 months seemed to receive a greater QOL benefit than those who died or withdrew.

A systematic review of factors influencing older adults' decision to accept or decline cancer treatment.

BACKGROUND: Cancer is a disease that affects mostly older adults. Older adults often have other chronic health conditions in addition to cancer and may have different health priorities, both of which can impact cancer treatment decision-making. However, no systematic review of factors that influence an older cancer patient's decision to accept or decline cancer treatment has been conducted. MATERIALS AND METHODS: Systematic review of the literature published between inception of the databases and February 2013. Dutch, English, French or German articles reporting on qualitative studies, cross-sectional, longitudinal observational or intervention studies describing factors why older adults accepted or declined cancer treatment examining actual treatment decisions were included. Ten databases were used. Two independent reviewers reviewed manuscripts and performed data abstraction using a standardized form and the quality of studies was assessed with the Mixed Methods Appraisal Tool. RESULTS: Of 17,343 abstracts reviewed, a total of 38 studies were included. The majority focused on breast and prostate cancer treatment decisions and most studies used a qualitative design. Important factors for accepting treatment were convenience and success rate of treatment, seeing necessity of treatment, trust in the physician and following the physician's recommendation. Factors important for declining cancer treatment included concerns about the discomfort of the treatments, fear of side effects and transportation difficulties. CONCLUSION: Although the reasons why older adults with cancer accepted or declined treatment varied considerably, the most consistent determinant was physician recommendation. Further studies using large, representative samples and exploring decision-making incorporating health literacy and comorbidity are needed.

The impact of cancer therapy on cognition in the elderly.

Cancer and cancer therapy-related cognitive impairment (formerly known as chemobrain or chemo-fog) are often described in the literature. In the past, studies have failed to prove the existence of cancer therapy-related cognitive dysfunction. However, more recently, prospective trials have shown that patients undergoing chemotherapy do display impairment in specific cognitive domains. Aging confers an increased risk of developing cancer, as well as cognitive impairment. The Geriatric Oncology clinic of the Segal Cancer Centre, Jewish General Hospital in Montreal was founded in 2006 to address the unique needs of older cancer patients. We will describe two cases of cancer therapy-related cognitive impairment from our Geriatric Oncology clinic. The first case is that of a 75 year old male diagnosed with stage III non-small cell lung carcinoma who complained of forgetfulness since starting carboplatin-paclitaxel. The second case is that of a 65 year old female diagnosed with stage I, estrogen-receptor-positive breast cancer who had undergone lumpectomy followed by adjuvant cyclophosphamide, methotrexate and fluorouracil chemotherapy, radiation therapy and was on exemestane when she was evaluated. We will also briefly review the literature of cancer therapy-related cognitive impairment.

Difficulties in decision making regarding chemotherapy for older cancer patients: A census of cancer physicians.

INTRODUCTION: The management of older cancer patients is often suboptimal. This study aims to understand the management of older cancer patients who may receive chemotherapy. METHODS: A questionnaire was mailed in 2006-2007 to 181 medical oncologists and hematologists practicing in the Province of Quebec, Canada. Physicians, involved in treatment decisions regarding chemotherapy in cancer patients aged 70 years and older, were eligible. RESULTS: The response rate was 45.7%. Treatment toxicity (24.4%), comorbidities (20.5%), and lack of social support (10.9%) were reported as challenges when caring for older cancer patients. Comorbidities and functional status were reported as principal factors when making treatment decisions regarding chemotherapy; 77.5% of respondents expressed interest in collaborating with geriatricians. CONCLUSIONS: The concerns of respondents about comorbidities, functional status, and social support, along with their interest to collaborate with geriatricians, support the need for a partnership between these two disciplines.

Usefulness of frailty markers in the assessment of the health and functional status of older cancer patients referred for chemotherapy: a pilot study.

BACKGROUND: Older cancer patients seen in an oncology clinic seem to be healthier and less disabled than traditional geriatric patients. Choosing the most sensitive tools to assess their health status is a major issue. This cross-sectional study explores the usefulness of frailty markers in detecting vulnerability in older cancer patients. METHODS: The study included cancer patients >or=70 years old referred to an oncology clinic for chemotherapy. Information on comorbidities, disability in instrumental activities of daily living (IADL) and activities of daily living (ADL), and seven frailty markers (nutrition, mobility, strength, energy, physical activity, mood, and cognition) was collected. Patients were classified into four hierarchical groups: 1- No frailty markers, IADL, or ADL disability; 2- Presence of frailty markers without IADL or ADL disability; 3- IADL disability without ADL disability; 4- ADL disability. RESULTS: Among the 50 patients assessed, 6 (12.0%) were classified into Group 1, 21 (42.0%) into Group 2, 15 (30.0%) into Group 3, and 8 (16.0%) into Group 4. In Group 2, 7 patients (33.3 %) had one frailty marker, and 14 (66.7%) had two or more. The most prevalent of the frailty markers were nutrition, mobility, and physical activity. CONCLUSION: The assessment of seven frailty markers allowed the detection of potential vulnerability among 42% of older cancer patients that would not have been detected through an assessment of IADL and ADL disability alone. A longitudinal study is needed to determine whether the use of frailty markers can better characterize the older cancer population and predict adverse outcomes due to cancer treatment.