Association between Geriatric 8 frailty and health-related quality of life in older patients with cancer (PROGNOSIS-G8): a Danish single-centre, prospective cohort study.

Health-related quality of life (HRQoL) is highly valued among older adults with cancer. The Geriatric 8 screening tool identifies individuals with frailty, but its association with HRQoL remains sparsely investigated. Herein, we evaluate whether Geriatric 8 frailty is associated with short-term and long-term HRQoL in older patients with cancer. In this Danish single-centre, prospective cohort study, patients aged 70 years and older, referred to oncological assessment for solid cancers, were screened with the Geriatric 8. Patients completed the European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Core 30 (QLQ-C30) and Elderly 14 (ELD14) questionnaires at baseline, 3 months, 6 months, 9 months, and 12 months. Patient characteristics were obtained from medical records. Differences in mean global health status and QoL (GHS), measured using the two seven-point Likert scale questions from the EORTC QLQ-C30 regarding overall health and QoL during the past week, between patients with frailty (defined as a Geriatric 8 score of ≤14) and without frailty within 12 months were the primary outcome. Secondary outcomes were differences in the mean EORTC Summary Score comprised of all questions from the QLQ-C30 except for those included in the GHS and a question concerning financial difficulties, and five functional (physical, role, and social functioning, maintaining purpose, and family support from the EORTC QLQ-C30 and the EORTC-QLQ-ELD14), and five symptom scales (fatigue, pain, mobility, future worries, and burden of illness from the EORTC-QLQ-C30 and the EORTC-QLQ-ELD14). Analyses were done using linear mixed models. All primary and secondary outcomes were adjusted for gender, treatment intent, and cancer type and the primary outcome was also assessed by means of a responder analysis. Between June 1, 2020 and Oct 15, 2021, 1398 eligible patients were screened with the Geriatric 8 (908 [65%] with frailty and 490 [35%] without frailty) and provided medical record data. Of these patients, 707 (51%) also provided HRQoL data (437 [62%] with frailty and 270 [38%] without frailty). When adjusted, patients with frailty had poorer GHS (-15·1, 95% CI -18·5 to -11·6; p<0·0001) at baseline and throughout follow-up (3 months -7·4, -11·0 to -3·7, p=0·0001; 6 months -11·7, -15·5 to -7·9, p<0·0001; 9 months -10·4, -14·3 to -6·5, p<0·0001; 12 months -10·4, -14·6 to -6·2, p<0·0001) compared to patients without frailty. Adjusted summary scores were also poorer for patients with frailty (-9·9, 95% CI -12·1 to -7·6; p<0·0001) compared to patients without frailty at baseline and throughout follow-up (3 months -8·2, -10·5 to -5·8, p=0·0001; 6 months -9·0, -11·4 to -6·6, p<0·0001; 9 months -9·2, -11·7 to -6·8, p<0·0001; 12 months -8·9, -11·5 to -6·3, p<0·0001). Patients with frailty had significantly worse physical and role functioning, mobility, and fatigue outcomes, with no differences in family support within 12 months, at all timepoints. Older patients with cancer and frailty have significantly poorer HRQoL than those without frailty within the 12 months following an oncology referral. Thus, by identifying and treating frailty, we can ultimately improve patient HRQoL. The Danish Cancer Society, Academy of Geriatric Cancer Research (AgeCare), Odense University Hospital, University of Southern Denmark, Dagmar Marshalls Fond, and Agnes and Poul Friis Fond.

Ditzel HM ，Giger AW ，Lund CM ，Ditzel HJ ，Möller S ，Pfeiffer P ，Ryg J ，Ewertz M ，Jørgensen TL ... -  《The Lancet Healthy Longevity》

Frailty is associated with decline in health-related quality of life of patients treated for head and neck cancer.

To determine the effect of frailty on Health Related Quality of Life (HRQoL) after treatment for Head and Neck Cancer (HNC). Patients were prospectively included in OncoLifeS, a data-biobank. Before treatment, patients underwent geriatric screening, including the Groningen Frailty Indicator (GFI) and Geriatric 8 (G8). Patients' HRQoL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) at three, six, twelve and twenty four months after treatment. Linear mixed models were used for statistical analysis. All models were adjusted for baseline HRQoL values, relevant confounders at baseline and yielded estimates (β), 95% confidence intervals and p-values. 288 patients were included. The mean age was 68.4 years and 68.8% were male. During follow-up, 84 patients had tumor recurrence and 66 died. Response to EORTC-QLQ-C30 ranged from 77.3% to 87.8%. Frail patients, defined by GFI, had significantly worse Global Health Status/Quality of Life (GHS/QoL) (β = -8.70(-13.54;-3.86), p < 0.001), physical functioning (β = -4.55(-8.70;-0.40), p < 0.032), emotional functioning (β = -20.06(-25.65;-15.86), p < 0.001), and social functioning (β = -8.44(-13.91;-2.98), p < 0.003) three months after treatment compared to non-frail patients. Furthermore, frail patients had a significantly worse course of GHS/QoL (β = -7.47(-11.23;-3.70), p = 0.001), physical functioning (β = -3.28(-6.26;-0.31), p = 0.031) and role functioning (β = -7.27(-12.26;-2.28), p = 0.005) over time, compared to non-frail patients. When frailty was determined by G8, frailty was significantly associated with worse GHS/QoL (β = -6.68(-11.00;-2.37), p = 0.003) and emotional functioning (β = -5.08(-9.43;-0.73), p = 0.022) three months after treatment. Frail patients are at increased risk for decline in HRQoL, and further deterioration during follow-up after treatment for HNC.

de Vries J ，Bras L ，Sidorenkov G ，Festen S ，Steenbakkers RJHM ，Langendijk JA ，Witjes MJH ，van der Laan BFAM ，de Bock GH ，Halmos GB ... -  《-》

International validation of the EORTC QLQ-ELD14 questionnaire for assessment of health-related quality of life elderly patients with cancer.

Wheelwright S ，Darlington AS ，Fitzsimmons D ，Fayers P ，Arraras JI ，Bonnetain F ，Brain E ，Bredart A ，Chie WC ，Giesinger J ，Hammerlid E ，O'Connor SJ ，Oerlemans S ，Pallis A ，Reed M ，Singhal N ，Vassiliou V ，Young T ，Johnson C ... -  《-》

Health-related quality of life in patients with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer treated with first-line pembrolizumab versus chemotherapy (KEYNOTE-177): an open-label, randomised, phase 3 trial.

In the KEYNOTE-177 study, pembrolizumab monotherapy provided statistically significant and clinically meaningful improvements in progression-free survival versus chemotherapy as first-line treatment in patients with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer. To further support the efficacy and safety findings of the KEYNOTE-177 study, results of the health-related quality of life (HRQOL) analyses are reported here. KEYNOTE-177 is an open-label, randomised, phase 3 trial being done at 192 cancer centres in 23 countries, in patients aged 18 years and older with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer, with an Eastern Cooperative Oncology Group performance status of 0 or 1, and who had not received previous systemic therapy for metastatic disease. Eligible patients were randomly assigned (1:1) centrally by use of interactive voice response or integrated web response technology to receive pembrolizumab 200 mg intravenously every 3 weeks or investigator's choice chemotherapy (mFOLFOX6 [leucovorin, fluorouracil, and oxaliplatin] or FOLFIRI [leucovorin, fluorouracil, and irinotecan] intravenously every 2 weeks with or without intravenous bevacizumab or cetuximab). Patients and investigators were not masked to treatment assignment. The primary endpoints were progression-free survival (previously reported) and overall survival (data to be reported at the time of the final analysis). HRQOL outcomes were evaluated as prespecified exploratory endpoints. The analysis population comprised all randomly assigned patients who received at least one dose of study treatment and completed at least one HRQOL assessment. HRQOL outcomes were mean change from baseline to prespecified week 18 in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and EORTC Quality of Life Questionnaire-Colorectal 29 (EORTC QLQ-CR29) scale and item scores, and in the EuroQoL 5 Dimensions 3 Levels (EQ-5D-3L) visual analogue scale and health utility scores; the proportion of patients with improved, stable, or deteriorated scores from baseline to prespecified week 18 in EORTC QLQ-C30 scales and items; and time to deterioration in EORTC QLQ-C30 global health status/quality of life (GHS/QOL), physical functioning, social functioning, and fatigue scores and EORTC QLQ-CR29 urinary incontinence scores. The threshold for a small and clinically meaningful mean difference in EORTC QLQ-C30 score was 5-8 points. This study is registered with ClinicalTrials.gov, NCT02563002 and is ongoing; recruitment is closed. Between Feb 11, 2016, and Feb 19, 2018, 307 patients were enrolled and randomly assigned to receive pembrolizumab (n=153) or chemotherapy (n=154). The HRQOL analysis population comprised 294 patients (152 receiving pembrolizumab and 142 receiving chemotherapy). As of Feb 19, 2020, median time from randomisation to data cutoff was 32·4 months (IQR 27·7-37·8). Least squares mean (LSM) change from baseline to prespecified week 18 showed a clinically meaningful improvement in EORTC QLQ-C30 GHS/QOL scores with pembrolizumab versus chemotherapy (between-group LSM difference 8·96 [95% CI 4·24-13·69]; two-sided nominal p=0·0002). Median time to deterioration was longer with pembrolizumab versus chemotherapy for GHS/QOL (hazard ratio 0·61 [95% CI 0·38-0·98]; one-sided nominal p=0·019), physical functioning (0·50 [95% CI 0·32-0·81]; one-sided nominal p=0·0016), social functioning (0·53 [95% CI 0·32-0·87]; one-sided nominal p=0·0050), and fatigue scores (0·48 [95% CI 0·33-0·69]; one-sided nominal p<0·0001). Pembrolizumab monotherapy led to clinically meaningful improvements in HRQOL compared with chemotherapy in patients with previously untreated microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer. These data, along with the previously reported clinical benefits, support pembrolizumab as a first-line treatment option for this population. Merck Sharp & Dohme, a subsidiary of Merck & Co, Kenilworth, NJ, USA.

Andre T ，Amonkar M ，Norquist JM ，Shiu KK ，Kim TW ，Jensen BV ，Jensen LH ，Punt CJA ，Smith D ，Garcia-Carbonero R ，Sevilla I ，De La Fouchardiere C ，Rivera F ，Elez E ，Diaz LA Jr ，Yoshino T ，Van Cutsem E ，Yang P ，Farooqui M ，Le DT ... -  《-》

Predictive Value of Geriatric Oncology Screening and Geriatric Assessment in Older Patients with Solid Cancers: Protocol for a Danish prospective cohort study (PROGNOSIS-G8).

Older patients with cancer constitute a heterogeneous group with varying degrees of frailty; therefore, geriatric assessment with initial geriatric oncology screening is recommended. The Geriatric 8 (G8) and the modified Geriatric 8 (mG8) are promising screening tools with high accuracy and an association with survival. However, evidence is sparse regarding patient-centered outcomes. This protocol describes a study, which aims to address the predictive and prognostic value of the G8 and mG8, with quality of life (QoL) as the primary outcome. In this single-center prospective cohort study, patients, age ≥70 years with solid malignancies, will be screened with the G8 and mG8 prior to receiving 1st line antineoplastic treatment. Patients will contribute medical record data including; cancer type, Charlson comorbidity index score, performance status, and treatment intent, type, and dosage, at baseline. Patients will complete QoL questionnaires (EORTC QLQ-C30 and ELD-14) at baseline, 3, 6, 9, and 12-months follow-up. Two functional measurements (the 30-s chair stand test and the handgrip strength test) will be conducted at baseline to assess the added predictive and prognostic value. At 12 months follow-up, initially administered treatment and treatment adherence will be recorded and assessed with generalized linear models, while overall survival and cancer-specific survival will be assessed using survival analysis models with time-varying covariates. The relationship between frailty (G8 ≤ 14, mG8 ≥ 6) and QoL within 12 months will be examined using mixed regression models. Geriatric oncology screening may identify a subgroup of older patients with frailty, at risk of experiencing diminishing QoL and poor treatment adherence. With the proposed screening program, patients who require treatment modification and additional support to maintain their QoL may be identified. It is our hope, that these insights may facilitate the formation of national guidelines for the treatment of older patients with cancer. Registration:NCT04644874.

Ditzel HM ，Giger AW ，Lund CM ，Ditzel HJ ，Mohammadnejad A ，Pfeiffer P ，Ryg J ，Jørgensen TL ，Ewertz M ... -  《-》