Marije E. Hamaker

Frailty screening methods for predicting outcome of a comprehensive geriatric assessment in elderly patients with cancer: a systematic review

Comprehensive geriatric assessment (CGA) is done to detect vulnerability in elderly patients with cancer so that treatment can be adjusted accordingly; however, this process is time-consuming and pre-screening is often used to identify fit patients who are able to receive standard treatment versus those in whom a full CGA should be done. We aimed to assess which of the frailty screening methods available show the best sensitivity and specificity for predicting the presence of impairments on CGA in elderly patients with cancer. We did a systematic search of Medline and Embase, and a hand-search of conference abstracts, for studies on the association between frailty screening outcome and results of CGA in elderly patients with cancer. Our search identified 4440 reports, of which 22 publications from 14 studies, were included in this Review. Seven different frailty screening methods were assessed. The median sensitivity and specificity of each screening method for predicting frailty on CGA were as follows: Vulnerable Elders Survey-13 (VES-13), 68% and 78%; Geriatric 8 (G8), 87% and 61%; Triage Risk Screening Tool (TRST 1+; patient considered frail if one or more impairments present), 92% and 47%, Groningen Frailty Index (GFI) 57% and 86%, Fried frailty criteria 31% and 91%, Barber 59% and 79%, and abbreviated CGA (aCGA) 51% and 97%. However, even in case of the highest sensitivity, the negative predictive value was only roughly 60%. G8 and TRST 1+ had the highest sensitivity for frailty, but both had poor specificity and negative predictive value. These findings suggest that, for now, it might be beneficial for all elderly patients with cancer to receive a complete geriatric assessment, since available frailty screening methods have insufficient discriminative power to select patients for further assessment.

The Value of Geriatric Assessments in Predicting Treatment Tolerance and All-Cause Mortality in Older Patients With Cancer

BACKGROUND Awareness of the use of geriatric assessments for older patients with cancer is increasing. The aim of this review is to summarize all available evidence on the association between geriatric assessments and relevant oncologic outcomes. METHOD A systematic search was conducted in Medline and Embase of studies on geriatric assessment in oncology, focusing on the association between baseline assessment and outcome. RESULTS The literature search identified 2008 reports; 51 publications from 37 studies were selected for inclusion in the review. The quality of studies was heterogeneous and generally poor. A median of five geriatric conditions were assessed per study (interquartile range: 4-8). Little consistency was found in the results of the studies. Furthermore, different tools appear to be predictive depending on the outcome measure: frailty, nutritional status, and comorbidity assessed by the Cumulative Illness Rating Scale for Geriatrics were predictive for all-cause mortality; frailty was predictive for toxicity of chemotherapy; cognitive impairment and activities of daily living impairment were predictive for chemotherapy completion; and instrumental activities of daily living impairment was predictive for perioperative complications. CONCLUSION Although various geriatric conditions appear to be of some value in predicting outcome in elderly patients with cancer, the results are too inconsistent to guide treatment decisions. Further research is needed to elucidate the role of geriatric assessments in the oncologic decision-making process for these patients.

The effect of a geriatric evaluation on treatment decisions for older cancer patients--a systematic review.

Abstract Aim. The aim of this systematic review is to summarise all available data on the effect of a geriatric evaluation on the multidisciplinary treatment of older cancer patients, focussing on oncologic treatment decisions and the implementation of non-oncologic interventions. Methods. A systematic search in MEDLINE and EMBASE for studies on the effect of a geriatric evaluation on oncologic and non-oncologic treatment for older cancer patients. Results. Literature search identified 1654 reports (624 from Medline and 1030 from Embase), of which 10 studies were included in the review. Three studies used a geriatric consultation while seven used a geriatric assessment performed by a cancer specialist, healthcare worker or (research) nurse. Six studies addressed a change in oncologic treatment, the initial treatment plan was modified in a median of 39% of patients after geriatric evaluation, of which two thirds resulted in less intensive treatment. Seven studies focused on the implementation of non-oncologic interventions based on the results of the geriatric evaluation; all but one reported that interventions were suggested for over 70% of patients, even in studies that did not focus specifically on frail older patients. In the other study, implementation of non-oncologic interventions was left to the cancer specialists discretion. Conclusion. A geriatric evaluation has significant impact on oncologic and non-oncologic treatment decisions in older cancer patients and deserves consideration in the oncologic work-up for these patients.

Breast Cancer in the Elderly: Retrospective Study on Diagnosis and Treatment According to National Guidelines

Abstract:  We set out to investigate the level of accordance of diagnosis and treatment of elderly breast cancer patients with national guidelines and to study predictors of deviation. Data on patient and tumor variables were collected from charts of 166 patients aged 70 years and older, diagnosed at our hospital in 2002–2004. Diagnostic work‐up and treatment were compared with guidelines and reasons for deviation were recorded; 122 (74%) patients were diagnosed and treated in accordance with guidelines. Diagnosis was incomplete in 19 patients (11%). Surgery, radiotherapy, and hormonal therapy were withheld in 19 (11%), 11 (7%), and 9 (5%) patients, respectively. Guideline deviation was motivated in 18 patients (11%) (comorbidity n = 11, patients’ preferences n = 5, age n = 2), unmotivated in 18 (11%), and undeliberate in 8 (5%). Our study demonstrates that deviation from guidelines in elderly breast cancer patients mainly occurs due to a deliberate adjustment to patient’s comorbidity and preference.

The Value of a Comprehensive Geriatric Assessment for Patient Care in Acutely Hospitalized Older Patients with Cancer

INTRODUCTION A comprehensive geriatric assessment systematically collects information on geriatric conditions and is propagated in oncology as a useful tool when assessing older cancer patients. OBJECTIVES The objectives were: (a) to study the prevalence of geriatric conditions in cancer patients aged ≥ 65 years, acutely admitted to a general medicine ward; (b) to determine functional decline and mortality within 12 months after admission; and (c) to assess which geriatric conditions and cancer-related variables are associated with 12-month mortality. METHODS This was an observational cohort study of 292 cancer patients aged ≥ 65 years, acutely admitted to the general medicine and oncology wards of two university hospitals and one secondary teaching hospital. Baseline assessments included patient characteristics, reason for admission, comorbidity, and geriatric conditions. Follow-up at 3 and 12 months was aimed at functional decline (loss of one or more activities of daily living [ADL]) and mortality. RESULTS The median patient age was 74.9 years, and 95% lived independently; 126 patients (43%) had metastatic disease. A high prevalence of geriatric conditions was found for instrumental ADL impairment (78%), depressive symptoms (65%), pain (65%), impaired mobility (48%), malnutrition (46%), and ADL impairment (38%). Functional decline was observed in 8% and 33% of patients at 3 and 12 months, respectively. Mortality rates were 38% at 3 months and 64% at 12 months. Mortality was associated with cancer-related factors only. CONCLUSION In these acutely hospitalized older cancer patients, mortality was only associated with cancer-related factors. The prevalence of geriatric conditions in this population was high. Future research is needed to elucidate if addressing these conditions can improve quality of life.

Exclusion of Older Patients From Ongoing Clinical Trials for Hematological Malignancies: An Evaluation of the National Institutes of Health Clinical Trial Registry

INTRODUCTION Cancer societies, research cooperatives, and countless publications have urged the development of clinical trials that facilitate the inclusion of older patients and those with comorbidities. We set out to determine the characteristics of currently recruiting clinical trials with hematological patients to assess their inclusion and exclusion of elderly patients. METHODS The NIH clinical trial registry was searched on July 1, 2013, for currently recruiting phase I, II or III clinical trials with hematological malignancies. Trial characteristics and study objectives were extracted from the registry website. RESULTS Although 5% of 1,207 included trials focused exclusively on elderly or unfit patients, 69% explicitly or implicitly excluded older patients. Exclusion based on age was seen in 27% of trials, exclusion based on performance status was seen in 16%, and exclusion based on stringent organ function restrictions was noted in 51%. One-third of the studies that excluded older patients based on age allowed inclusion of younger patients with poor performance status; 8% did not place any restrictions on organ function. Over time, there was a shift from exclusion based on age (p value for trend <.001) toward exclusion based on organ function (p = .2). Industry-sponsored studies were least likely to exclude older patients (p < .001). CONCLUSION Notably, 27% of currently recruiting clinical trials for hematological malignancies use age-based exclusion criteria. Although physiological reserves diminish with age, the heterogeneity of the elderly population does not legitimize exclusion based on chronological age alone. Investigators should critically review whether sufficient justification exists for every exclusion criterion before incorporating it in trial protocols.

A randomized phase III study comparing pegylated liposomal doxorubicin with capecitabine as first-line chemotherapy in elderly patients with metastatic breast cancer: results of the OMEGA study of the Dutch Breast Cancer Research Group BOOG

BACKGROUND Prospective data on chemotherapy for elderly patients with metastatic breast cancer (MBC) remain scarce. We compared the efficacy and safety of first-line chemotherapy with pegylated liposomal doxorubicin (PLD) versus capecitabine in MBC patients aged ≥65 years in a multicentre, phase III trial. PATIENTS AND METHODS Patients were randomized to six cycles of PLD (45 mg/m2 every 4 weeks) or eight cycles of capecitabine (1000 mg/m2 twice daily, day 1-14 every 3 weeks). RESULTS The study enrolled 78 of the planned 154 patients and was closed prematurely due to slow accrual and supply problems of PLD. Many included patients were aged ≥75 years (54%) and vulnerable (≥1 geriatric condition: 71%). The median dose intensity was 85% for PLD and 84% for capecitabine, respectively. In both arms, the majority of patients completed at least 12 weeks of treatment (PLD 73%; capecitabine 74%). After a median follow-up of 39 months, 77 patients had progressed and 62 patients had died of MBC. Median progression-free survival was 5.6 versus 7.7 months (P = 0.11) for PLD and capecitabine, respectively. Median overall survival was 13.8 months for PLD and 16.8 months for capecitabine (P = 0.59). Both treatments were feasible, grade 3 toxicities consisting of fatigue (both arms: 13%), hand-foot syndrome (PLD: 10%; capecitabine: 16%), stomatitis (PLD: 10%; capecitabine: 3%), exanthema (PLD: 5%) and diarrhoea (PLD: 3%; capecitabine: 5%). Only 1 of 10 patients aged ≥80 years completed chemotherapy, while 3 and 6 patients discontinued treatment due to toxicity or progressive disease, respectively. CONCLUSION Both PLD and capecitabine demonstrated comparable efficacy and acceptable tolerance as first-line single-agent chemotherapy in elderly patients with MBC, even in vulnerable patients or patients aged ≥75 years. However, patients aged ≥80 years were unlikely to complete chemotherapy successfully. CLINICAL TRIAL NUMBERS EudraCT 2006-002046-10; ISRCTN 11114726; CKTO 2006-09; BOOG 2006-02.BACKGROUND Prospective data on chemotherapy for elderly patients with metastatic breast cancer (MBC) remain scarce. We compared the efficacy and safety of first-line chemotherapy with pegylated liposomal doxorubicin (PLD) versus capecitabine in MBC patients aged ≥65 years in a multicentre, phase III trial. PATIENTS AND METHODS Patients were randomized to six cycles of PLD (45 mg/m(2) every 4 weeks) or eight cycles of capecitabine (1000 mg/m(2) twice daily, day 1-14 every 3 weeks). RESULTS The study enrolled 78 of the planned 154 patients and was closed prematurely due to slow accrual and supply problems of PLD. Many included patients were aged ≥75 years (54%) and vulnerable (≥1 geriatric condition: 71%). The median dose intensity was 85% for PLD and 84% for capecitabine, respectively. In both arms, the majority of patients completed at least 12 weeks of treatment (PLD 73%; capecitabine 74%). After a median follow-up of 39 months, 77 patients had progressed and 62 patients had died of MBC. Median progression-free survival was 5.6 versus 7.7 months (P = 0.11) for PLD and capecitabine, respectively. Median overall survival was 13.8 months for PLD and 16.8 months for capecitabine (P = 0.59). Both treatments were feasible, grade 3 toxicities consisting of fatigue (both arms: 13%), hand-foot syndrome (PLD: 10%; capecitabine: 16%), stomatitis (PLD: 10%; capecitabine: 3%), exanthema (PLD: 5%) and diarrhoea (PLD: 3%; capecitabine: 5%). Only 1 of 10 patients aged ≥80 years completed chemotherapy, while 3 and 6 patients discontinued treatment due to toxicity or progressive disease, respectively. CONCLUSION Both PLD and capecitabine demonstrated comparable efficacy and acceptable tolerance as first-line single-agent chemotherapy in elderly patients with MBC, even in vulnerable patients or patients aged ≥75 years. However, patients aged ≥80 years were unlikely to complete chemotherapy successfully. CLINICAL TRIAL NUMBERS EudraCT 2006-002046-10; ISRCTN 11114726; CKTO 2006-09; BOOG 2006-02.

The chance of survival and the functional outcome after in-hospital cardiopulmonary resuscitation in older people: a systematic review

BACKGROUND physicians are frequently confronted with the question whether cardiopulmonary resuscitation (CPR) is a medically appropriate treatment for older people. For physicians, patients and relatives, it is important to know the chance of survival and the functional outcome after CPR in order to make an informed decision. METHODS a systematic search was performed in MEDLINE, Embase and Cochrane up to November 2012. Studies that were included described the chance of survival, the social status and functional outcome after in-hospital CPR in older people aged 70 years and above. RESULTS we identified 11,377 publications of which 29 were included in this review; 38.6% of the patients who were 70 years and older had a return of spontaneous circulation. More than half of the patients who initially survived resuscitation died in the hospital before hospital discharge. The pooled survival to discharge after in-hospital CPR was 18.7% for patients between 70 and 79 years old, 15.4% for patients between 80 and 89 years old and 11.6% for patients of 90 years and older. Data on social and functional outcome after surviving CPR were scarce and contradictory. CONCLUSIONS the chance of survival to hospital discharge for in-hospital CPR in older people is low to moderate (11.6-18.7%) and decreases with age. However, evidence about functional or social outcomes after surviving CPR is scarce. Prospective studies are needed to address this issue and to identify pre-arrest factors that can predict survival in the older people in order to define subgroups that could benefit from CPR.

Omission of surgery in elderly patients with early stage breast cancer

AIM To assess national trends over time in surgery for elderly patients with resectable breast cancer (BC) and to evaluate clinical outcome and cause of death after the omission of surgery in a regional cohort of elderly patients. METHODS National trends in 1995-2005 were calculated using cancer registry data. In addition, a chart review was performed in a cohort of patients aged ≥ 75 years, with early stage BC but no primary surgery, diagnosed at five Dutch hospitals in 1990-2005. Patient characteristics, comorbidity and reason for the omission of surgery were collected from the chart. Cause of death was retrieved from death certificate data registered at Statistics Netherlands. RESULTS Omission of surgery increased significantly over time for patients aged 80 years and older (p<0.05). Of the 187 patients in the regional cohort (median age 85.9 years (range 75.0-97.7), 174 (92%) received hormonal therapy. Omission of surgery was at the patients request in 59 patients (32%). Of the 178 patients that died during follow-up, 60 patients (34%) died of BC. For 81 patients (45%), BC was not clinically relevant at the time of death. Median overall survival was 2.3 years (range 0.2-10.7) and did not differ between BC and other causes of death (p=0.9). CONCLUSION Omission of surgery for elderly patients with resectable BC has increased significantly over the past decade; instead patients often received primary endocrine treatment. Although this may appear an effective alternative to surgery, the potential for a longer term negative impact on disease control and quality of life deserves further investigation.

Systematic comprehensive geriatric assessment in elderly patients on chronic dialysis: a cross-sectional comparative and feasibility study

BackgroundElderly dialysis patients are prone to disabilities and functional decline. This aggravates their last period of life. It would be valuable to be able to preserve daily function and quality of life. Identification of domains requiring additional attention is not common practice in standard care. Therefore, we performed a systematic Comprehensive Geriatric Assessment (CGA) to assess physical and psychosocial function and tested its feasibility in daily practice. The CGA is used more frequently in the assessment of elderly cancer patients, and we therefore compared the outcomes to this group.MethodsA cross-sectional, multicenter study, between June 1st and September 31st, 2009, in four Dutch outpatient dialysis units. Fifty patients aged 65 years or above who received dialysis because of end-stage renal disease (ESRD) were randomly included. We assessed the CGA during a systematic interview with patients and their caregivers. The cancer patients had had a similar CGA in an earlier study. We compared prevalences between groups.ResultsIn the dialysis population (68.0% 75 years or above, 76.6% on haemodialysis) caregivers often observed behavioral changes, such as deviant eating habits (34.0%) and irritability (27.7%). In 84.4%, caregivers felt overburdened by the situation of their family member. Somatic and psychosocial conditions were frequently found (polypharmacy (94.6%), depression (24.5%)) and prevalence of most geriatric conditions was comparable to those in elderly cancer patients.ConclusionsGeriatric conditions were highly prevalent among elderly dialysis patients and prevalences were comparable in both populations. The CGA proved feasible for recognition of these conditions and of overburdened caregivers. This could prevent further functional decline and preserve quality of life.