The course of depressive symptoms and mortality in older patients with cancer.

OBJECTIVE: The Geriatric Depression Scale (GDS-15), a self-report questionnaire, emphasizes the psychological dimension of depression. We aimed to investigate whether GDS-15 scores were associated with mortality in older patients with cancer and describe the course of individual symptoms on the GDS-15. METHODS: An observational, multicenter, prospective study of 288 patients 70 years or older with cancer followed over 24 months. The patients were assessed with the GDS-15 at inclusion, and after four and 12 months. An extended Cox regression model assessed the association between time-dependent GDS-15 scores and mortality. RESULTS: After adjusting for cancer-related prognostic factors, a one-point increase in GDS-15 sum score increased risk of death by 12%. GDS-15 mean score increased during the first four months of the study, as did odds for the presence of the GDS-15 symptoms 'feel you have more problems with memory than most', 'not feel full of energy', and 'think that most people are better off than you'. The most prevalent and persistent GDS-15 symptom was 'prefer to stay at home, rather than going out and doing new things', and 'not to be in good spirits most of the time' was the least prevalent. CONCLUSIONS: More severe depressive symptoms, as measured by the GDS-15, were associated with higher mortality in older patients with cancer. The importance of emotional distress and how to alleviate it should be investigated further in these patients.

CT Derived Muscle Measures, Inflammation, and Frailty in a Cohort of Older Cancer Patients.

BACKGROUND/AIM: Muscle loss, inflammation, and frailty are prevalent among older cancer patients. We aimed to evaluate whether inflammatory markers could identify muscle loss, and if muscle measures differed between frail and non-frail patients. PATIENTS AND METHODS: A total of 115 patients ≥70 years old with solid tumors were included. Inflammation was measured using the Glasgow Prognostic Score (GPS), which is based on C-reactive protein (CRP) and albumin levels, and CRP alone. Frailty was evaluated using a modified geriatric assessment (mGA) of eight domains affecting older patients' health status. Computed tomography-derived muscle measures were collected at the level of the third lumbar vertebra. RESULTS: Patients with GPS=2 and CRP>27 mg/l exhibited poorer muscle measures compared to patients with lower levels. No associations between mGA-based frailty and muscle mass were found. CONCLUSION: Inflammation has detrimental effects on muscle mass. However, GPS or CRP alone cannot be used to identify muscle loss, and muscle measures were not associated with frailty in this series.

Arti Hurria and the progress in integrating the geriatric assessment into oncology: Young International Society of Geriatric Oncology review paper.

Until recently, the progress in the diagnosis and management of cancer has not been matched by similar progress in the assessment of the increasing numbers of older and more complex patients with cancer. Dr. Arti Hurria identified this gap at the outset of her career, which she dedicated toward studying the geriatric assessment (GA) as an improvement over traditional methods used in oncology to assess vulnerability in older patients with cancer. This review documents the progress of the GA and its integration into oncology. First, we detail the GA's origins in the field of geriatrics. Next, we chronicle the early rise of geriatric oncology, highlighting the calls of early thought-leaders to meet the demands of the rapidly aging cancer population. We describe Dr. Hurria's early efforts toward meeting these calls though the implementation of the GA in oncology research. We then summarize some of the seminal studies constituting the evidence base supporting GA's implementation. Finally, we lay out the evolution of cancer-focused guidelines recommending the GA, concluding with future needs to advance the next steps toward more widespread implementation in routine cancer care. Throughout, we describe Dr. Hurria's vision and its execution in driving progress of the GA in oncology, from her fellowship training to her co-authored guidelines recommending GA for all older adults with cancer-published in the year of her untimely death.

Reproducibility of semiautomated body composition segmentation of abdominal computed tomography: a multiobserver study.

BACKGROUND: Segmentation of computed tomography (CT) images provides quantitative data on body tissue composition, which may greatly impact the development and progression of diseases such as type 2 diabetes mellitus and cancer. We aimed to evaluate the inter- and intraobserver variation of semiautomated segmentation, to assess whether multiple observers may interchangeably perform this task. METHODS: Anonymised, unenhanced, single mid-abdominal CT images were acquired from 132 subjects from two previous studies. Semiautomated segmentation was performed using a proprietary software package. Abdominal muscle compartment (AMC), inter- and intramuscular adipose tissue (IMAT), visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were identified according to pre-established attenuation ranges. The segmentation was performed by four observers: an oncology resident with extensive training and three radiographers with a 2-week training programme. To assess interobserver variation, segmentation of each CT image was performed individually by two or more observers. To assess intraobserver variation, three of the observers did repeated segmentations of the images. The distribution of variation between subjects, observers and random noise was estimated by a mixed effects model. Inter- and intraobserver correlation was assessed by intraclass correlation coefficient (ICC). RESULTS: For all four tissue compartments, the observer variations were far lower than random noise by factors ranging from 1.6 to 3.6 and those between subjects by factors ranging from 7.3 to 186.1. All interobserver ICC was ≥ 0.938, and all intraobserver ICC was ≥ 0.996. CONCLUSIONS: Body composition segmentation showed a very low level of operator dependability. Multiple observers may interchangeably perform this task with highly reproducible results.

Modifiable factors affecting older patients' quality of life and physical function during cancer treatment.

BACKGROUND: Maintaining physical function and quality of life (QoL) are prioritized outcomes among older adults. We aimed to identify potentially modifiable factors affecting older patients' physical function and QoL during cancer treatment. METHODS: Prospective, multicenter study of 307 patients with cancer ≥70 years, referred for systemic treatment. Pre-treatment, a modified geriatric assessment (mGA) was performed, including registration of comorbidities, medications, nutritional status, cognitive function, depressive symptoms (Geriatric Depression Scale-15 [GDS]), and mobility (Timed Up and Go [TUG]). Patient-reported physical function (PF)-, global QoL-, and symptom scores were assessed at baseline, two, four, and six months by the EORTC Quality of Life Core Questionnaire-C30. The impact of mGA components and symptoms on patients' PF and global QoL scores during six months was investigated by linear mixed models. To identify groups following distinct PF trajectories, a growth mixture model was estimated. RESULTS: 288 patients were eligible, mean age was 76.9 years, 68% received palliative treatment. Higher GDS-scores and poorer TUG were independently associated with an overall level of poorer PF and global QoL throughout follow-up, as were more pain, dyspnea, and appetite loss, and sleep disturbance. Three groups with distinct PF trajectories were identified: a poor group exhibiting a non-linear statistically (p < .001) and clinically significant decline (≥10 points), an intermediate group with a statistically (p = .003), but not clinically significant linear decline, and a good group with a stable trajectory. Higher GDS-scores and poorer TUG, more pre-treatment pain and dyspnea were associated with higher odds of belonging to the poor compared to the good PF group. CONCLUSION: Depressive symptoms, reduced mobility, and more physical symptoms increased the risk of decrements in older patients' PF and global QoL scores during cancer treatment, and represent potential targets for interventions aiming at improving these outcomes.

Screening for frailty among older patients with cancer using blood biomarkers of inflammation.

INTRODUCTION: As frailty is associated with inflammation, biomarkers of inflammation may represent objective measures that could facilitate the identification of frailty. Glasgow prognostic score (GPS), combines C-reactive protein (CRP) and albumin, and is scored from 0 to 2 points. Higher score indicates a higher degree of inflammation. OBJECTIVES: To investigate whether (1) GPS is associated with frailty, (2) GPS could be used to screen for frailty, (3) IL-6 and TNF-α add to the accuracy of GPS as a screening tool, and (4) GPS adds prognostic information in frail older patients with cancer. METHODS: Prospective, observational study of 255 patients ≥70 years with solid malignant tumours referred for medical cancer treatment. At baseline, frail patients were identified by a modified Geriatric Assessment (mGA), and blood samples were collected. RESULTS: Mean age was 76.7 years, 49.8% were frail, and 56.1% had distant metastases. The proportion of frail patients increased with higher GPS (GPS zero: 43.2%, GPS one: 52.7%, GPS two: 94.7%). GPS two was significantly associated with frailty (OR 18.5), independent of cancer type, stage, BMI and the use of anti-inflammatory drugs. The specificity of GPS was high (99%), but the sensitivity was low (14%). Frail patients with GPS two had poorer survival than patients with GPS zero-one. TNF-α and IL-6 did not improve the accuracy of GPS when screening for frailty. CONCLUSION: Frailty and GPS two are strongly associated, and GPS two is a significant prognostic factor in frail, older patients with cancer. The inflammatory biomarkers investigated are not suitable screening tools for frailty.

Geriatric assessment is superior to oncologists' clinical judgement in identifying frailty.

BACKGROUND: Frailty is a syndrome associated with increased vulnerability and an important predictor of outcomes in older cancer patients. Systematic assessments to identify frailty are seldom applied, and oncologists' ability to identify frailty is scarcely investigated. METHODS: We compared oncologists' classification of frailty (onc-frail) based on clinical judgement with a modified geriatric assessment (mGA), and investigated associations between frailty and overall survival. Patients ⩾70 years referred for medical cancer treatment were eligible. mGA-frailty was defined as impairment in at least one of the following: daily activities, comorbidity, polypharmacy, physical function or at least one geriatric syndrome (cognitive impairment, depression, malnutrition, falls). RESULTS: Three hundred and seven patients were enroled, 288 (94%) completed the mGA, 286 (93%) were rated by oncologists. Median age was 77 years, 56% had metastases, 85% performance status (PS) 0-1. Overall, 104/286 (36%) were onc-frail and 140/288 (49%) mGA-frail, the agreement was fair (kappa value 0.30 (95% CI 0.19; 0.41)), and 67 mGA-frail patients who frequently had localised disease, good PS and received curative treatment, were missed by the oncologists. Only mGA-frailty was independently prognostic for survival (HR 1.61, 95% CI 1.14; 2.27; P=0.007). CONCLUSIONS: Systematic assessment of geriatric domains is needed to aid oncologists in identifying frail patients with poor survival.