Ulrich Wedding

Screening tools for multidimensional health problems warranting a geriatric assessment in older cancer patients: an update on SIOG recommendations†

BACKGROUND Screening tools are proposed to identify those older cancer patients in need of geriatric assessment (GA) and multidisciplinary approach. We aimed to update the International Society of Geriatric Oncology (SIOG) 2005 recommendations on the use of screening tools. MATERIALS AND METHODS SIOG composed a task group to review, interpret and discuss evidence on the use of screening tools in older cancer patients. A systematic review was carried out and discussed by an expert panel, leading to a consensus statement on their use. RESULTS Forty-four studies reporting on the use of 17 different screening tools in older cancer patients were identified. The tools most studied in older cancer patients are G8, Flemish version of the Triage Risk Screening Tool (fTRST) and Vulnerable Elders Survey-13 (VES-13). Across all studies, the highest sensitivity was observed for: G8, fTRST, Oncogeriatric screen, Study of Osteoporotic Fractures, Eastern Cooperative Oncology Group-Performance Status, Senior Adult Oncology Program (SAOP) 2 screening and Gerhematolim. In 11 direct comparisons for detecting problems on a full GA, the G8 was more or equally sensitive than other instruments in all six comparisons, whereas results were mixed for the VES-13 in seven comparisons. In addition, different tools have demonstrated associations with outcome measures, including G8 and VES-13. CONCLUSIONS Screening tools do not replace GA but are recommended in a busy practice in order to identify those patients in need of full GA. If abnormal, screening should be followed by GA and guided multidisciplinary interventions. Several tools are available with different performance for various parameters (including sensitivity for addressing the need for further GA). Further research should focus on the ability of screening tools to build clinical pathways and to predict different outcome parameters.

End Points and Trial Design in Geriatric Oncology Research: A Joint European Organisation for Research and Treatment of Cancer–Alliance for Clinical Trials in Oncology–International Society of Geriatric Oncology Position Article

Selecting the most appropriate end points for clinical trials is important to assess the value of new treatment strategies. Well-established end points for clinical research exist in oncology but may not be as relevant to the older cancer population because of competing risks of death and potentially increased impact of therapy on global functioning and quality of life. This article discusses specific clinical end points and their advantages and disadvantages for older individuals. Randomized or single-arm phase II trials can provide insight into the range of efficacy and toxicity in older populations but ideally need to be confirmed in phase III trials, which are unfortunately often hindered by the severe heterogeneity of the older cancer population, difficulties with selection bias depending on inclusion criteria, physician perception, and barriers in willingness to participate. All clinical trials in oncology should be without an upper age limit to allow entry of eligible older adults. In settings where so-called standard therapy is not feasible, specific trials for older patients with cancer might be required, integrating meaningful measures of outcome. Not all questions can be answered in randomized clinical trials, and large observational cohort studies or registries within the community setting should be established (preferably in parallel to randomized trials) so that treatment patterns across different settings can be compared with impact on outcome. Obligatory integration of a comparable form of geriatric assessment is recommended in future studies, and regulatory organizations such as the European Medicines Agency and US Food and Drug Administration should require adequate collection of data on efficacy and toxicity of new drugs in fit and frail elderly subpopulations.

Tolerance to Chemotherapy in Elderly Patients With Cancer

BACKGROUND Due to demographic changes, the number of elderly people with cancer will increase in the next decades. In the past, elderly patients with cancer were often excluded from clinical trials. Chronological age has been considered a risk factor for increased toxicity and reduced tolerance to chemotherapy. METHODS We present a review on toxicity of chemotherapy and factors associated with toxicity in elderly patients with cancer, and we discuss chemotherapeutic agents and treatment options in treating this patient population. RESULTS Age is a risk factor for increased toxicity to chemotherapy and decreased tolerance. However, few trials have been reported with adjustment for age-associated changes such as impairment of functional status and increased comorbidity, which also show an independent association with increased toxicity. Published data may include several biases, such as referral and publication bias. CONCLUSIONS Decision making in elderly cancer patients should be based on the results of a geriatric assessment. Patients with few or no limitations should be treated as younger patients are treated. Data with a high level of evidence are unavailable for patients showing moderate or severe limitations in a geriatric assessment.

Comprehensive Geriatric assessment in the elderly cancer patient

The proportion of older cancer patients is increasing due to demographic and disease-specific reasons. However, this group of patients is severely underrepresented in research and clinical therapy. Limitation in physical and functional capacity with considerable interindividual heterogeneity remains one of the important problems in the treatment decision process. One approach to this problem is the use of a Comprehensive Geriatric Assessment (CGA) to describe and classify these deficits with high validity and reliability. The different domains of CGA are described with special respect to the instruments applied, as CGA has also a key role in the decision process.

Clinical impact of nucleophosmin mutations and Flt3 internal tandem duplications in patients older than 60 yr with acute myeloid leukaemia

Background:  Nucleophosmin (NPM1) and Flt3 internal tandem duplications (Flt3‐ITD mutations) represent the most frequent molecular aberrations in patients with acute myeloid leukemia (AML). While NPM1 mutations are associated with favourable prognosis in younger AML patients, Flt3‐ITD mutations reflect an unfavourable prognostic factor in these patients. So far, especially NPM1 mutations have not yet been evaluated exclusively in older patients.

Prevalence of anemia in elderly patients in primary care: impact on 5-year mortality risk and differences between men and women

ABSTRACT Background: Increased mortality in patients with anemia has been demonstrated in disabled, seriously ill or hospitalized patients. In industrialized nations with their aging societies, however, elderly but apparently healthy family-physician patients are an important demographic group from a public-health perspective. We therefore set out to evaluate the prevalence of anemia in this group and associations between anemia and 5-year all-cause mortality, adjusted for multiple other established risk factors and chronic diseases. Methods: This was a monitored, prospective cohort study in Germany with 344 representative family physicians who documented, consecutively, elderly patients (aged ≥ 65 years). Extensive fasting plasma parameters were collected at baseline. Anemia at inclusion was defined according to World Health Organization criteria (hemoglobin below 12 g/dl in women and 13 g/dl in men). All participants were followed up for death of any cause for 5.3 years. Results: Among the 6880 individuals, 2905 men and 3975 women, aged 65–95 (mean age 72.5), mild anemia (hemoglobin levels ≥10 g/dl) was found in 6.1% of women and 8.1% of men. Among those patients, 36.1% of anemic men and 15.0% of anemic women died. In a Cox proportional hazards analysis, multiple adjusted for potential confounders including major comorbidities, a near doubling of the 5-year mortality risk in anemic men (hazard ratio [HR] 1.9; 95% confidence interval [CI] 1.5–2.4) was found, while in anemic women there was no risk increase at all (HR 1.1; 95% CI 0.8–1.6). Even if patients with the lowest hemoglobin concentration (<11 g/dl for women, <12 g/dl for men) are singled out for multiple-adjusted analysis, anemia in men was related to a significant mortality risk (HR 3.3; 95% CI 2.1–5.1), but not in women (HR 1.85; 95% CI 0.97–3.53). Conclusion: In typical elderly patients without severe comorbidities, mild anemia was significantly associated with greater mortality in men but not in women. Given the impact of sex on outcomes of older subjects with mild anemia, the current definition of anemia should be adjusted for elderly males towards a higher hemoglobin threshold. Interventional trials will be needed to determine whether a consistent correction of anemia improves mortality of older men.

Evaluation of geriatric assessment in patients with chronic lymphocytic leukemia: Results of the CLL9 trial of the German CLL study group

Abstract Multidimensional geriatric assessment (GA) has been demonstrated to predict outcomes in older patients with cancer. This study evaluated GA in a cohort of older patients with chronic lymphocytic leukemia (CLL). Seventy-five of 97 subjects with CLL who were enrolled in a clinical trial of the German CLL Study Group underwent GA prior to the start of study treatment (low-dose chemotherapy with fludarabine). GA included cumulative illness rating scale (CIRS), timed-up-and-go (TUG) test, dementia detection (DEMTECT) test and instrumental activities of daily living (IADL) index. There was little correlation between CIRS, TUG, DEMTECT or IADL results and treatment toxicity, feasibility or efficacy in this study. CIRS and IADL had no statistically significant impact on overall prognosis. However, under-performance in TUG or DEMTECT test was strongly associated with poor survival. The latter findings provide a rationale to further investigate geriatric assessment in CLL and in the context with other CLL treatments.

Use of Hematopoietic Growth Factors in Elderly Patients Receiving Cytotoxic Chemotherapy

Myelosuppression is a common side effect in elderly patients undergoing chemotherapy. Neutropenia and anemia cause considerable morbidity, may increase mortality, and can result in a worse outcome of treatment in elderly patients compared to younger patients with comparable type and stage of disease. The availability and proven efficacy of hematopoietic growth factors such as granulocyte colonystimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO) have had a considerable impact on supportive care in cancer patients: Several randomized trials have demonstrated a reduction of neutropenia and the frequency of severe infections in elderly patients treated with G-CSF following myelotoxic chemotherapy compared with patients without growth factor support. Both for G-CSF and for recombinant human erythropoietin (rHu-EPO) several studies have demonstrated the safety and effectiveness of these molecules in elderly patients with regard to increasing hemoglobin concentrations, improving quality of life (rHu-EPO), and neutrophil recovery. Although a positive effect of the use of growth factors on overall survival in elderly cancer patients is not yet proven, a reduction of chemotherapy-induced side effects could clearly be shown. The National Comprehensive Cancer Network (NCCN) of cancer centers has recommended that all patients aged 70 years and older treated with CHOP or cytotoxic chemotherapy of comparable intensity should receive prophylactic G-CSF administration, and that the hemoglobin concentration be maintained at ≧12 g/dl in elderly patients undergoing chemotherapy.

Advances in the Pharmacological Treatment of Gastro-Oesophageal Cancer

Despite a sharp decline in the incidence of gastric cancer during the second half of the 20th century, this malignancy remains the second leading cause of cancer mortality in the world. The incidence and mortality rate of gastric cancer increase with age; at present, the median ages at diagnosis are 67 years for men and 72 years for women in the US. This article reviews and discusses current medical treatment options for both the general population and elderly gastric cancer patients.Management of localized gastric cancer has changed significantly over recent years. Adjuvant chemoradiation is not generally recommended outside the US. After decades of trials of adjuvant chemotherapy with inconclusive results, a significant survival benefit for perioperative combination chemotherapy — as compared with surgery alone — in patients with resectable or locally advanced gastro-oesophageal cancer was recently demonstrated in the UK MAGIC trial. A further large, randomized trial from Japan demonstrated a significant survival benefit for adjuvant chemotherapy with S-1 after D2 resection for gastric cancer. However, both trials are applicable only to the population in which the trials were conducted. Specific data on elderly patients are missing.For patients with metastatic disease, oral fluoropyrimidines, such as capecitabine, have been developed. In Asian patients, treatment with the oral fluoropyrimidine S-1 is safe and effective. Docetaxel, oxaliplatin and irinotecan have demonstrated activity against gastric cancer in appropriately designed, randomized, phase III trials and have increased the available treatment options significantly. In addition, according to preliminary data, trastuzumab in combination with chemotherapy has significantly improved activity when compared to chemotherapy alone in patients with human epidermal receptor (HER)-2-positive gastric and gastro-oesophageal cancers. Thus, therapeutic decisions in patients with advanced gastric cancer may be adapted to the molecular subtype and co-morbidities of the individual patient. Data from retrospective analyses suggest that oxaliplatin seems to be better tolerated than cisplatin in elderly patients.

Chemotherapy in Elderly Patients with Advanced Lung Cancer Part II: Treatment of Non-Small Cell Lung Cancer (NSCLC)

Increasing interest in the treatment of elderly patients or patients with poor performance status (PS) with non-small cell lung cancer (NSCLC) has led to a number of subgroup analyses of clinical trials, and even more importantly, the conduction of trials specifically designed for this cohort. These studies allow some important conclusions. Data from retrospective studies and meta-analyses indicate that the use of platinum-based two-drug combinations in selected, fit elderly patients may produce response rates, survival, and toxicity comparable to those in younger patients. This excludes a per se inferior effectiveness of chemotherapy in the population of elderly patients with NSCLC. A number of more recently introduced agents with a favourable toxicity profile have significantly increased treatment options. Single- agent therapy with vinorelbine, when compared to best supportive care, has been shown to give a statistically significant survival benefit and improve quality of life. Conflicting data from phase II/III trials in elderly patients with NSCLC exist regarding a potential benefit of combination chemotherapy over single-agent treatment in the total cohort of elderly patients, including those with comorbidities or declining functional reserve. A review of the most important trials, assessing treatment options in elderly patients with lung cancer, either prospectively or retrospectively, is provided, and still unresolved issues are addressed.