Barbara L. van Leeuwen

International Society of Geriatric Oncology Consensus on Geriatric Assessment in Older Patients With Cancer

PURPOSE To update the International Society of Geriatric Oncology (SIOG) 2005 recommendations on geriatric assessment (GA) in older patients with cancer. METHODS SIOG composed a panel with expertise in geriatric oncology to develop consensus statements after literature review of key evidence on the following topics: rationale for performing GA; findings from a GA performed in geriatric oncology patients; ability of GA to predict oncology treatment–related complications; association between GA findings and overall survival (OS); impact of GA findings on oncology treatment decisions; composition of a GA, including domains and tools; and methods for implementing GA in clinical care. RESULTS GA can be valuable in oncology practice for following reasons: detection of impairment not identified in routine history or physical examination, ability to predict severe treatment-related toxicity, ability to predict OS in a variety of tumors and treatment settings, and ability to influence treatment choice and intensity. The panel recommended that the following domains be evaluated in a GA: functional status, comorbidity, cognition, mental health status, fatigue, social status and support, nutrition, and presence of geriatric syndromes. Although several combinations of tools and various models are available for implementation of GA in oncology practice, the expert panel could not endorse one over another. CONCLUSION There is mounting data regarding the utility of GA in oncology practice; however, additional research is needed to continue to strengthen the evidence base.

Postoperative cognitive dysfunction: Involvement of neuroinflammation and neuronal functioning.

Postoperative cognitive dysfunction (POCD) has been hypothesized to be mediated by surgery-induced inflammatory processes, which may influence neuronal functioning either directly or through modulation of intraneuronal pathways, such as the brain derived neurotrophic factor (BDNF) mediated pathway. To study the time course of post-surgical (neuro)inflammation, changes in the BDNF-pathway and POCD, we subjected 3months old male Wistar rats to abdominal surgery and implanted a jugular vein catheter for timed blood sampling. Cognition, affective behavior and markers for (neuro)inflammation, BDNF and neurogenesis were assessed at 1, 2 and 3weeks following surgery. Rats displayed changes in exploratory activity shortly after surgery, associated with postoperatively elevated IL-6 plasma levels. Spatial learning and memory were temporarily impaired in the first 2weeks following surgery, whereas non-spatial cognitive functions seemed unaffected. Analysis of brain tissue revealed increased neuroinflammation (IL-1B and microgliosis) 7days following surgery, decreased BDNF levels on postoperative day 14 and 21, and decreased neurogenesis until at least 21days following surgery. These findings indicate that in young adult rats only spatial learning and memory is affected by surgery, suggesting hippocampal dependent cognition is especially vulnerable to surgery-induced impairment. The observed differences in time course following surgery and relation to plasma IL-6 suggest cognitive dysfunction and mood changes comprise distinct features of postoperative behavioral impairment. The postoperative changes in neuroinflammation, BDNF and neurogenesis may represent aspects of the underlying mechanism for POCD. Future research should be aimed to elucidate how these players interact.

Thinking through postoperative cognitive dysfunction: How to bridge the gap between clinical and pre-clinical perspectives.

Following surgery, patients may experience cognitive decline, which can seriously reduce quality of life. This postoperative cognitive dysfunction (POCD) is mainly seen in the elderly and is thought to be mediated by surgery-induced inflammatory reactions. Clinical studies tend to define POCD as a persisting, generalised decline in cognition, without specifying which cognitive functions are impaired. Pre-clinical research mainly describes early hippocampal dysfunction as a consequence of surgery-induced neuroinflammation. These different approaches to study POCD impede translation between clinical and pre-clinical research outcomes and may hamper the development of appropriate interventions. This article analyses which cognitive domains deteriorate after surgery and which brain areas might be involved. The most important outcomes are: (1) POCD encompasses a wide range of cognitive impairments; (2) POCD affects larger areas of the brain; and (3) individual variation in the vulnerability of neuronal networks to neuroinflammatory mechanisms may determine if and how POCD manifests itself. We argue that, for pre-clinical and clinical research of POCD to advance, the effects of surgery on various cognitive functions and brain areas should be studied. Moreover, in addition to general characteristics, research should take inter-relationships between cognitive complaints and physical and mental characteristics into account.

Timed Up & Go: A Screening Tool for Predicting 30-Day Morbidity in Onco-Geriatric Surgical Patients? A Multicenter Cohort Study

Objective To determine the predictive value of the “Timed Up & Go” (TUG), a validated assessment tool, on a prospective cohort study and to compare these findings to the ASA classification, an instrument commonly used for quantifying patients’ physical status and anesthetic risk. Background In the onco-geriatric surgical population it is important to identify patients at increased risk of adverse post-operative outcome to minimize the risk of over- and under-treatment and improve outcome in this population. Methods 263 patients ≥70 years undergoing elective surgery for solid tumors were prospectively recruited. Primary endpoint was 30-day morbidity. Pre-operatively TUG was administered and ASA-classification was registered. Data were analyzed using multivariable logistic regression analyses to estimate odds ratios (OR) and 95% confidence intervals (95%-CI). Absolute risks and area under the receiver operating characteristic curves (AUC’s) were calculated. Results 164 (62.4%) patients (median age: 76) underwent major surgery. 50 (19.5%) patients experienced major complications. 50.0% of patients with high TUG and 24.8% of patients with ASA≥3 experienced major complications (absolute risks). TUG and ASA were independent predictors of the occurrence of major complications (TUG:OR 3.43; 95%-CI = 1.13–10.36. ASA1 vs. 2:OR 5.67; 95%-CI = 0.86–37.32. ASA1 vs. 3&4:OR 11.75; 95%-CI = 1.62–85.11). AUCTUG was 0.66 (95%-CI = 0.57–0.75, p<0.001) and AUCASA was 0.58 (95%-CI = 0.49–0.67, p = 0.09). Conclusions Twice as many onco-geriatric patients at risk of post-operative complications, who might benefit from pre-operative interventions, are identified using TUG than when using ASA.

Structured analyses of interventions to prevent delirium.

Delirium is one of the most serious complications in hospitalized elderly, with incidences ranging from 3–56%. The objective of this meta‐analysis was two‐fold, first to investigate if interventions to prevent delirium are effective and second to explore which factors increase the effectiveness of these interventions.

The effect of under-treatment of breast cancer in women 80 years of age and older

BACKGROUND Several authors have demonstrated a trend toward the under-treatment of elderly and very elderly women with breast cancer. This study was undertaken to determine the impact of under-treatment of breast cancer in women age 80 and older. METHODS A retrospective chart review of all patients 80 years and older with a newly diagnosed breast cancer at the MD Anderson Cancer Center, Houston, TX, between September 1, 1989 and September 1, 2004 was performed. Data extracted from charts included patient demographics, comorbidity, treatments recommended, treatments received, complications of therapy, disease recurrence and disease related death. Treatments undertaken were analyzed in the context of accepted therapy at the time of diagnosis. RESULTS Two hundred twelve patients were identified. The median age was 83.5 years (range 80-97). Overall survival in the entire cohort was 7.28 years with a median follow up of 4 years for patients still alive at the end of the study period. Fifty seven percent of patients were under-treated according to institutional and national guidelines. Women who underwent hormonal therapy only demonstrated decreased disease specific survival (P<0.001 respectively) compared with patients who received multi-modality therapy. Women who underwent partial mastectomy without radiation treatment experienced a significant increase in local regional recurrence (P=0.045). There was an association of increased disease specific survival in patients who had surgical lymph node evaluation compared to those who did not (P=0.04). CONCLUSIONS Outcomes are compromised in very elderly women with breast cancer in whom less than complete combined modality treatment is undertaken. With the previously demonstrated safety of radiation therapy, hormonal therapy and surgery in the very elderly population, multi-modality therapy should not be routinely withheld in patients in this age category.

Postoperative cognitive dysfunction and microglial activation in associated brain regions in old rats

Research indicates that neuroinflammation plays a major role in postoperative cognitive dysfunction (POCD) in older patients. However, studies have mainly focused on hippocampal neuroinflammation and hippocampal-dependent learning and memory, which does not cover the whole spectrum of POCD. We hypothesized that regional differences in postoperative neuroinflammation in the brain may underlie variation in postoperative cognitive impairment. We aimed to investigate this hypothesis in a rat-model for POCD, by analyzing postoperative impairment in behavioral task performance and microglial activation in related brain areas. We subjected 25 months old Wistar rats to surgery and assessed spatial learning and memory, object and location recognition, reversal learning and exploratory behavior in the second postoperative week. The number and morphology of microglia were analyzed in the hippocampus, prefrontal cortex, striatum and amygdala on postoperative day 14. Control groups consisted of 3 and 25 months old rats that did not undergo surgery. We observed age related impairment in learning, memory and behavior, which was aggravated following surgery. Additionally, in old rats surgery was associated with signs of classical microglial activation in brain areas related to the impaired cognitive functions. These outcomes suggest that indeed neuroinflammation may be involved in POCD. Moreover, effects of age and surgery on cognition and microglial morphology seem to be area specific and hence cannot be generalized to the whole brain. This underpins the importance for expanding the research of POCD beyond the hippocampus.

The effect of age and gender on outcome after treatment for colon carcinoma A population-based study in the Uppsala and Stockholm region

RATIONALE The aim of this study was to assess whether there are differences in treatment strategy and outcome between different age cohorts among men and women with colon cancer. METHODS All patients with colon cancer included in the regional quality registry in Uppsala/Orebro and Stockholm between 1996 and December 2004 were analysed (n=11002). Patients were divided into three age categories: < or =65 years, 66-80 years and >80 years. RESULTS Overall and cancer-specific survival decreased with increasing age for stages II and III colon cancer but was not influenced by gender. Older patients with stage III tumours were less likely to be referred for chemotherapeutic treatment and there was a decrease in cancer-specific survival with increasing age, from 63.7% to 51.0% to 38.4% in the three age groups. Postoperative morbidity and the number of reoperations was significantly higher in men than in women. CONCLUSION The present study shows lower cancer-specific survival among older patients than among younger patients. Gender was not a prognostic factor in cancer-specific survival.

Outcomes of a Geriatric Liaison Intervention to Prevent the Development of Postoperative Delirium in Frail Elderly Cancer Patients: Report on a Multicentre, Randomized, Controlled Trial

Background Delirium is a serious and common postoperative complication, especially in frail elderly patients. The aim of this study was to evaluate the effect of a geriatric liaison intervention in comparison with standard care on the incidence of postoperative delirium in frail elderly cancer patients treated with an elective surgical procedure for a solid tumour. Methods Patients over 65 years of age who were undergoing elective surgery for a solid tumour were recruited to a multicentre, prospective, randomized, controlled trial. The patients were randomized to standard treatment versus a geriatric liaison intervention. The intervention consisted of a preoperative geriatric consultation, an individual treatment plan targeted at risk factors for delirium, daily visits by a geriatric nurse during the hospital stay and advice on managing any problems encountered. The primary outcome was the incidence of postoperative delirium. The secondary outcome measures were the severity of delirium, length of hospital stay, complications, mortality, care dependency, quality of life, return to an independent preoperative living situation and additional care at home. Results In total, the data of 260 patients were analysed. Delirium occurred in 31 patients (11.9%), and there was no significant difference between the incidence of delirium in the intervention group and the usual-care group (9.4% vs. 14.3%, OR: 0.63, 95% CI: 0.29–1.35). Conclusions Within this study, a geriatric liaison intervention based on frailty for the prevention of postoperative delirium in frail elderly cancer patients undergoing elective surgery for a solid tumour has not proven to be effective. Trial Registration Nederlands Trial Register Trial ID NTR 823

Surgery-induced behavioral changes in aged rats

Elderly patients may experience impairments in cognition or mood following surgery. To study the development and underlying mechanisms of these postoperative behavioral changes, young (3 months) and aged (18-20 months) male rats were subjected to abdominal surgery followed by behavioral testing during a period of 6 weeks. Microglia activation (IBA-1) and neurogenesis (DCX) were immunohistochemically determined. In separate experiments, the effects of anesthesia and the cytokine response (IL-6) following surgery were evaluated. Increased age was associated with changes in affective behavior, decreased cognitive flexibility and increased microglia activation as well as increased weight loss and plasma IL-6 following surgery. No effects of surgery on cognition were observed at either age. However, aged rats displayed long-term changes in affective behavior and had increased microgliosis in the CA1 hippocampal region following surgery. Microglia activation following surgery was positively correlated to parameters of behavior and spatial learning. These findings support the hypothesis that elderly patients have an increased behavioral and (neuro)inflammatory response to surgery and these factors may be related.