Effect of comprehensive geriatric assessment on hospitalizations in older adults with frailty initiating curatively intended oncologic treatment: The PROGNOSIS-RCT study.

INTRODUCTION: Frailty constitutes a risk for unplanned hospitalizations in older adults with cancer. This study examines whether comprehensive geriatric assessment (CGA) as an add-on to standard oncologic care can prevent unplanned hospitalizations in older adults with frailty and cancer who initiate curative oncological treatment. MATERIALS AND METHODS: This randomized controlled trial included older adults aged ≥70 with frailty (Geriatric 8 [G8] ≤14), and solid cancers who initiated curative oncological treatment. Participants were randomized 1:1 to either standard oncologic care (control) or standard oncologic care supplemented with CGA-guided interventions (intervention). Baseline characteristics were retrieved prior to randomization. The primary endpoint, the between-group rate ratio of unplanned hospitalizations within six months of treatment initiation, was analyzed using negative binominal regression. Analyses were performed using an intention-to-treat approach, followed by per-protocol analysis, including participants receiving CGA within 30 days of randomization, and preplanned subgroup analyses based on treatment modality and Geriatric 8 screening. Secondary endpoints included acute hospital contacts, treatment adherence, and toxicity. RESULTS: From November 1, 2020 to May 31, 2023, 173 participants were enrolled. Median age was 75 (interquartile range 72-79), 51.5% were female, 58% had a G8 score > 12, and 84% had Eastern Cooperative Oncology Group performance status 0-1. The most common cancer sites were lung (23%), upper gastrointestinal (15%), and breast (13%). The rate (per person-years) of unplanned hospitalization was 1.32 in the intervention group and 1.81 in the control group, with a between-group rate ratio of 0.74 (95% confidence interval [CI] 0.45-1.23, P = 0.25) favoring the intervention. The between-group rate ratio increased in the per-protocol analysis (0.64 [95% CI 0.37-1.10, P = 0.10]). Similarly, no significant between group differences were found in treatment adherence, rate of acute hospital contacts, or toxicity. DISCUSSION: In this study, CGA did not significantly reduce the rate of unplanned hospitalizations. Furthermore, no between-group differences were found in treatment adherence, toxicity lead hospitalizations, or treatment completion in older adults with cancer and frailty. However, per-protocol analysis suggests that increasing adherence to CGA may improve the outcome. Larger studies ensuring higher CGA adherence are warranted to confirm our findings.

Physical decline, falls, and hospitalization among vulnerable older patients in the trajectory of colorectal cancer treatment.

INTRODUCTION: Resilience to anticancer treatment for colorectal cancer (CRC) among older patients varies. Many experience weight loss, physical decline, falls, and hospitalization during treatment, often leading to early discontinuation of otherwise effective chemotherapy. Screening for vulnerability might help to identify patients at risk of these adverse outcomes in older adults. MATERIALS AND METHODS: This is a secondary analysis from the GERICO trial. Patients aged ≥70 years assessed for chemotherapy for CRC were screened for eligibility for the GERICO trial with the geriatric-8 (G8) frailty screening tool. The present study population comprised patients who were (1) screened with G8 but for reasons not included in the GERICO study and (2) patients who were randomized to the GERICO control group. We evaluated whether patients identified as vulnerable with G8 (≤14/17) or retrospectively constructed mG8 (≥6/35) had higher risk of experiencing decline in performance status (PS), falls, and unplanned hospitalization during treatment. The association between frailty status and the adverse outcomes was analyzed with univariate and multivariate logistic regression. The discriminative ability of G8/mG8 to predict outcomes was analyzed using the area under the curve for receiver operating characteristics curves. RESULTS: In total, 238 patients (median age 74 years [range 70-91]) were included in this analysis. More vulnerable than fit patients experienced decline in PS (G8: 41% vs. 14%, p = 0.006 and mG8: 28% vs. 17%, p = 0.04) during treatment. Furthermore, more vulnerable than fit patients experienced falls (G8 14% vs. 6% p = 0.04) and unplanned hospitalization (G8: 31% vs. 14%, p = 0.009 and mG8: 34% vs. 13%, p < 0.001). Multivariate analyses showed an association between G8 vulnerability and decline in PS, falls, and hospitalization. DISCUSSION: Patients with G8 or mG8 vulnerability were more likely to experience decline in PS and unplanned hospitalization during chemotherapy for CRC than fit patients. More G8 vulnerable patients experienced falls compared with fit patients. Appropriate interventions should be offered to older patients with CRC assessed as vulnerable with G8 or mG8 to maintain PS during chemotherapy.

The SaVe project - Sarcopenia and Vertigo in aging patients with colorectal cancer: A study protocol for three randomized controlled trials.

INTRODUCTION: Older patients with cancer range from fit to frail with various comorbidities and resilience to chemotherapy. Besides nausea and fatigue, a significant number of patients experience dizziness and impaired walking balance after chemotherapy, which can have great impact on their functional ability and health related quality of life. Symptoms are easily overlooked and therefore often underreported and managed, which is why symptoms could end up as long-lasting side effects. The aim of this study is to investigate the development of dizziness, decline in walking balance, and sarcopenia and the effect of a comprehensive geriatric assessment and 12 weeks of group-based exercise on these symptoms. The exercise intervention includes vestibular and balance exercises, and progressive resistance training, to counteract the symptoms in older patients with colorectal cancer treated with chemotherapy. MATERIALS AND METHODS: This is a randomized controlled trial including patients ≥65 years initiating (neo)adjuvant or first-line palliative chemotherapy for colorectal cancer. Patients will undergo a comprehensive assessment program including measures of vestibular function, balance, muscle strength, mass, and endurance, peripheral and autonomic nerve function, and subjective measures of dizziness, concern of falling, and health related quality of life. Tests will be performed at baseline, 12, and 24 weeks. Patients will be placed in three different randomized controlled trials depending on chemotherapy regimen and randomized 1:1 to comprehensive geriatric assessment and exercise three times/week or control. Participants in both groups will continue with usual care, including standardized oncological treatment. In total, 150 patients are needed to assess the two primary outcomes of (1) maintenance of walking balance assessed with Dynamic Gait Index and (2) lower limb strength and endurance assessed with 30 Second Sit-to-Stand Test at 12 weeks. The primary outcomes will be analyzed using a mixed linear regression model investigating the between-group differences. DISCUSSION: Trial enrollment began in April 2023 and is the first trial to evaluate reasons for dizziness, decline in walking balance, and sarcopenia in older patients receiving chemotherapy. The trial will provide new and valuable knowledge in how to assess, manage, and prevent dizziness, decline in walking balance, and sarcopenia in older patients with colorectal cancer. TRIAL REGISTRATION: The Regional Ethics Committee (j.nr. H-22064206). Danish Data Protection Agency (P-2023-86) and ClinicalTrials.gov (NCT05710809).

Impact of FRAilty screening and Geriatric assessment and INtervention in older patients with epithelial Ovarian Cancer: A multicenter randomized clinical trial protocol (FRAGINOC).

INTRODUCTION: Radical surgery combined with chemotherapy is the only potential curative treatment of patients with advanced epithelial ovarian cancer (EOC). However, 43% of older Danish patients with EOC are not referred to surgery due to frailty, age, or fear of complications. Comprehensive geriatric assessment (CGA) has demonstrated ability to reduce frailty in older patients, but there is a knowledge gap regarding its effect before or during treatment in older adults with EOC. This protocol presents a randomized controlled trial (RCT), which evaluates the effect of CGA-based interventions including individualized physical exercise therapy in older adults with EOC during neoadjuvant chemotherapy (NACT). MATERIALS AND METHODS: This RCT will include patients aged ≥70 years with primary EOC referred to NACT. Patients will be randomized 1:1 to intervention or standard of care, along with neoadjuvant antineoplastic treatment. Stratification for performance status and center of inclusion will be performed. In the intervention arm, a geriatrician will perform CGA and corresponding geriatric interventions and patients will undergo an individualized home-based exercise program managed by a physiotherapist. All patients will be evaluated with Geriatric-8, modified Geriatric-8, clinical frailty scale, and physical tests at randomization. Predictive values (positive/negative) will be evaluated for CGA detected impairments. The primary endpoint is the proportion of patients referred to interval debulking surgery (IDS). Secondary endpoints include the proportion who complete oncological treatment, improvements in physical tests, quality of life measured by European Organization for Research and Treatment of Cancer-Quality of Life questionnaires at inclusion, after three cycles of chemotherapy, and at end of chemotherapy treatment. Furthermore, the association between results of geriatric screening tests, CGA, and physical tests with complication rate and progression free survival will be examined. The primary outcome will be analyzed with logistic regression in the intention-to-treat population. Power calculations reveal the need to enroll 216 patients. DISCUSSION: The present study examines whether CGA-based interventions including individualized physical exercise can increase the referral rate for potential curative IDS in older patients with EOC. If successful, this will result in more patients undergoing surgery and completing chemotherapy, preventing complications, and ultimately improving quality of life and survival. The study setup may establish the basis for direct clinical implementation if proven effective.

Geriatric screening and frailty intervention in older patients with cancer.

Frailty in older patients with cancer increases the risk of treatment related toxicity, mortality, physical decline, and quality of life. This review summarises various screening tools. Screening tools identifying frailty serve multiple purposes, providing awareness of health issues impacting oncologic treatment and prognosis and facilitating the delivery of a Comprehensive Geriatric Assessment (CGA). CGA is an overall health assessment and treatment targeting frailty. Providing CGA to older patients with cancer reduces the risk of toxicity and functional decline, increases treatment completion, and prevents loss of quality of life.