Tolerability and effectiveness of palbociclib in older women with metastatic breast cancer.

PURPOSE: Palbociclib has become the standard of care for estrogen receptor-positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer, but real-world evidence in older women remains scarce. Therefore, we investigated tolerability of palbociclib in older women with metastatic breast cancer. METHODS: Consecutive women aged ≥ 70 with ER+/HER2- metastatic breast cancer, treated with palbociclib in any treatment line in six hospitals, were included. Primary endpoint was grade ≥ 3 palbociclib-related toxicity. Predictors of toxicity were identified using logistic regression models. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan Meier. RESULTS: We included 144 women with a median age of 74 years. Grade 3-4 toxicity occurred in 54% of patients, of which neutropenia (37%) was most common. No neutropenic fever or grade 5 toxicity occurred. Dose reduction during treatment occurred in 50% of patients, 8% discontinued treatment due to toxicity and 3% were hospitalized due to toxicity. Polypharmacy (odds ratio (OR) 2.50; 95% confidence interval (CI) 1.12-5.58) and pretreatment low leukocytes (OR 4.81; 95% CI 1.27-18.21) were associated with grade 3-4 toxicity, while comorbidities were not. In first-line systemic therapy, median PFS was 12 months and median OS 32 months. In second-line, median PFS was 12 months and median OS 31 months. CONCLUSION: Although grade 3-4 toxicity and dose reductions occurred frequently, most were expected and managed by dose reductions, showing that palbociclib is generally well tolerated and thus represents a valuable treatment option in the older population.

Shared decision-making with older adults with cancer: Adaptation of a model through literature review and expert opinion.

OBJECTIVE: To provide a literature overview of characteristics of Shared Decision Making (SDM) with specific importance to the older adult population with cancer and to tailor an existing model of SDM in patients with cancer to the needs of older adults. METHODS: A systematic search of several databases was conducted. Eligible studies described factors influencing SDM concerning cancer treatment with adults aged 65 years or above, with any type of cancer. We included qualitative or mixed-methods studies. Themes were identified and discussed in an expert panel, including a patient-representative, until consensus was reached on an adjusted model. RESULTS: Overall 29 studies were included and nine themes were identified from the literature. The themes related to the importance of goal setting, need for tailored information provision, the role of significant others, uncertainty of evidence, the importance of time during and outside of consultations, the possible ill-informed preconceptions that health care professionals (HCPs) might have about older adults and the specific competencies they need to engage in the SDM process with older adults. No new themes emerged from discussion with expert panel. This study presents a visual model of SDM with older patients with cancer based on the identified themes. CONCLUSIONS: Our model shows key elements that are specific to SDM with older adults. Further research needs to focus on how to educate HCPs on the competencies needed to engage in SDM with older patients, and how to implement the model into everyday practice.

Older people's goals of care in relation to frailty status-the COOP-study.

BACKGROUND: Literature relating older people's goals of care to their varying frailty status is scarce. OBJECTIVE: To investigate goals of care in case of acute and/or severe disease in relationship to frailty status among the general older population. METHOD: Older people aged ≥70 in the Netherlands completed a questionnaire. They were divided into three subgroups based on a self-reported Clinical Frailty Scale: fit (CFS 1-3), mildly frail (CFS 4-5) and severely frail (CFS 6-8). Seven goals were graded as unimportant (1-5), somewhat important (6-7) or very important (8-10): extending life, preserving quality of life (QoL), staying independent, relieving symptoms, supporting others, preventing hospital admission and preventing nursing home admission. RESULTS: Of the 1,278 participants (median age 76 years, 63% female), 57% was fit, 32% mildly frail and 12% severely frail. Overall, participants most frequently considered preventing nursing home admission as very important (87%), followed by staying independent (84%) and preserving QoL (83%), and least frequently considered extending life as very important (31%). All frailty subgroups reported similar preferences out of the surveyed goals as the overall study population. However, participants with a higher frailty status attached slightly less importance to each individual goal compared with fit participants (Ptrend-values ≤ 0.037). CONCLUSION: Preferred goals of care are not related to frailty status, while the importance ascribed to individual goals is slightly lower with higher frailty status. Future research should prioritise outcomes related to the shared goals of fit, mildly frail and severely frail older people to improve personalised medicine for older patients.

Association of Biological Age with Tumor Microenvironment in Patients with Esophageal Adenocarcinoma.

INTRODUCTION: Esophageal cancer is the seventh most common cancer worldwide and typically tends to manifest at an older age. Marked heterogeneity in time-dependent functional decline in older adults results in varying grades of clinically manifest patient fitness or frailty. The biological age-related adaptations that accompany functional decline have been shown to modulate the non-malignant cells comprising the tumor microenvironment (TME). In the current work, we studied the association between biological age and TME characteristics in patients with esophageal adenocarcinoma. METHODS: We comparatively assessed intratumoral histologic stroma quantity, tumor immune cell infiltrate, and blood leukocyte and thrombocyte count in 72 patients stratified over 3 strata of biological age (younger <70 years, fit older ≥70 years, and frail older adults ≥70 years), as defined by a geriatric assessment. RESULTS: Frailty in older adults was predictive of decreased intratumoral stroma quantity (B = -14.66% stroma, p = 0.022) relative to tumors in chronological-age-matched fit older adults. Moreover, in comparison to younger adults, frail older adults (p = 0.032), but not fit older adults (p = 0.302), demonstrated a lower blood thrombocyte count at the time of diagnosis. Lastly, we found an increased proportion of tumors with a histologic desert TME histotype, comprising low stroma quantity and low immune cell infiltration, in frail older adults. CONCLUSION: Our results illustrate the stromal-reprogramming effects of biological age and provide a biological underpinning for the clinical relevance of assessing frailty in patients with esophageal adenocarcinoma, further justifying the need for standardized geriatric assessment in geriatric cancer patients.

Frequency of use and characterization of frailty assessments in observational studies on older women with breast cancer: a systematic review.

BACKGROUND: Breast cancer and frailty frequently co-occur in older women, and frailty status has been shown to predict negative health outcomes. However, the extent to which frailty assessments are utilized in observational research for the older breast cancer population is uncertain. Therefore, the aim of this review was to determine the frequency of use of frailty assessments in studies investigating survival or mortality, and characterize them, concentrating on literature from the past 5 years (2017-2022). METHODS: MEDLINE, EMBASE and Cochrane Library were systematically queried to identify observational studies (case-control, cohort, cross-sectional) published from 2017-2022 that focus on older females (≥ 65 years) diagnosed with breast cancer, and which evaluate survival or mortality outcomes. Independent reviewers assessed the studies for eligibility using Covidence software. Extracted data included characteristics of each study as well as information on study design, study population, frailty assessments, and related health status assessments. Risk of bias was evaluated using the appropriate JBI tool. Information was cleaned, classified, and tabulated into review level summaries. RESULTS: In total, 9823 studies were screened for inclusion. One-hundred and thirty studies were included in the final synthesis. Only 11 (8.5%) of these studies made use of a frailty assessment, of which 4 (3.1%) quantified frailty levels in their study population, at baseline. Characterization of frailty assessments demonstrated that there is a large variation in terms of frailty definitions and resulting patient classification (i.e., fit, pre-frail, frail). In the four studies that quantified frailty, the percentage of individuals classified as pre-frail and frail ranged from 18% to 29% and 0.7% to 21%, respectively. Identified frailty assessments included the Balducci score, the Geriatric 8 tool, the Adapted Searle Deficits Accumulation Frailty index, the Faurot Frailty index, and the Mian Deficits of Accumulation Frailty Index, among others. The Charlson Comorbidity Index was the most used alternative health status assessment, employed in 56.9% of all 130 studies. Surprisingly, 31.5% of all studies did not make use of any health status assessments. CONCLUSION: Few observational studies examining mortality or survival outcomes in older women with breast cancer incorporate frailty assessments. Additionally, there is significant variation in definitions of frailty and classification of patients. While comorbidity assessments were more frequently included, the pivotal role of frailty for patient-centered decision-making in clinical practice, especially regarding treatment effectiveness and tolerance, necessitates more deliberate attention. Addressing this oversight more explicitly could enhance our ability to interpret observational research in older cancer patients.

Time trends in treatment patterns and survival of older patients with synchronous metastatic colorectal cancer in the Netherlands: A population-based study.

New treatment strategies have improved survival of metastatic colorectal cancer in trials. However, it is not clear whether older patients benefit from these novel therapies, as they are often not included in pivotal trials. Therefore, we investigated treatment patterns and overall survival over time in older patients with metastatic colorectal cancer in a population-based study. We identified 22.192 Dutch patients aged ≥70 years diagnosed with synchronous metastatic colorectal cancer between 2005 and 2020 from the Netherlands Cancer Registry. Changes in treatment over time were assessed with logistic regression models. Survival was assessed by Cox proportional hazard ratios (HR). Results showed that chemotherapy use increased between 2005 and 2015, but declined from 2015 onwards, while more patients received best supportive care. Over time, fewer patients underwent primary tumor resection alone. Although survival of both metastatic colon and rectal cancer improved until 2014, survival of colon cancer decreased from 2014 onwards (HR 1.04, 95% confidence interval [CI] 1.01-1.05), which was seen in all age groups. Survival of metastatic rectal cancer patients remained unchanged from 2014 onwards (HR 1.00, 95% CI 0.98-1.03) in all age groups. In conclusion, treatment patterns of Dutch older patients with synchronous metastatic colorectal cancer rapidly changed from 2005 to 2020, with increasing percentages of patients receiving best supportive care. Survival of metastatic colon cancer decreased from 2014 onwards. The implementation of a colorectal cancer screening program and patient selection might explain why only a subset of older patients seem to benefit from the availability of novel treatment options.

Temporal changes in characteristics and external validity of randomized controlled trials in older people from 2012 to 2019.

BACKGROUND: Older individuals are often underrepresented in clinical trials. In 2012 only 7% of RCT's specifically studied older people and their geriatric characteristics were poorly reported. The aim of this review was to investigate temporal changes in characteristics and external validity of randomized controlled trials in older people from 2012 to 2019. METHODS: PubMed was searched for randomized clinical trials (RCTs) published in 2019. Firstly, the proportion of RCTs specially designed for older people were determined by the following criteria: a reported mean age of ≥ 70 years or a lower age cutoff of ≥ 55. Secondly, the trials with a majority of older people, defined by a reported mean age of ≥ 60 years, were screened for reporting of geriatric assessments. Both parts were compared with identical reviews performed in 2012. RESULTS: From a 10% random sample, 1446 RCTs were included in this systematic review. First, 8% of trials were specifically designed for older people in 2019 compared to 7% in 2012. Secondly, 25% of the trials included a majority of older people in 2019, compared to 22% in 2012. Thirdly, in 52% of these trials in 2019 one or more of the geriatric assessments were reported compared to 34% in 2012. CONCLUSIONS: Although in 2019 the proportion of published RCTs specifically designed for older people remains low, more characteristics on geriatric assessments were reported compared to 2012. Continued efforts should be paid to increase both the number and the validity of trials for older people.

Frailty and checkpoint inhibitor toxicity in older patients with melanoma.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) that range from mild to life-threatening. Age itself does not seem to be a predictor for the occurrence of irAEs. It is unknown whether frailty plays a role in the occurrence of irAEs. Therefore, the authors assessed whether irAEs and their sequelae occur more often in frail patients than in fit patients according to the Geriatric 8 (G8) assessment. METHODS: Patients with melanoma aged 70 years and older who were about to start ICI therapy and were screened with the G8 assessment were enrolled in this prospective, observational study. Patients were classified by the G8 as either fit or frail. The primary outcome was the occurrence of grade ≥3 irAEs. RESULTS: In total, 92 patients were included for statistical analyses, 26 (29%) of whom were classified as frail. Grade ≥3 irAEs occurred in 20% of patients. There was no significant difference in the occurrence of grade ≥3 irAEs between fit and frail patients (17% vs 27%; P = .26). Frail patients were admitted to the hospital because of irAEs significantly more often than fit patients (29% vs 54%; P = .02) and showed a trend toward increased length of hospitalization (5 vs 8 days; P = .06) and more frequent use of immunosuppressants or ICI discontinuation for irAEs (36% vs 58%; P = .06). CONCLUSIONS: Although frailty appears to be unrelated to the occurrence of severe irAEs, it is an indicator of irAE-related adverse sequelae, such as hospital admission. Screening for frailty can be of added value in the shared decision-making process for older patients who qualify for ICI treatment.

Discontinuation of adjuvant endocrine therapy and impact on quality of life and functional status in older patients with breast cancer.

PURPOSE: Side effects are the main reason for discontinuation of adjuvant endocrine therapy in older adults. The aim of this study was to examine geriatric predictors of treatment discontinuation of adjuvant endocrine therapy within the first 2 years after initiation, and to study the association between early discontinuation and functional status and quality of life (QoL). METHODS: Patients aged ≥ 70 years with stage I-III breast cancer who received adjuvant endocrine therapy were included. The primary endpoint was discontinuation of endocrine therapy within 2 years. Risk factors for discontinuation were assessed using univariate logistic regression models. Linear mixed models were used to assess QoL and functional status over time. RESULTS: Overall, 258 patients were included, of whom 36% discontinued therapy within 2 years after initiation. No geriatric predictive factors for treatment discontinuation were found. Tumour stage was inversely associated with early discontinuation. Patients who discontinued had a worse breast cancer-specific QoL (b = - 4.37; 95% CI - 7.96 to - 0.78; p = 0.017) over the first 2 years, in particular on the future perspective subscale (b = - 11.10; 95% CI - 18.80 to - 3.40; p = 0.005), which did not recover after discontinuation. Treatment discontinuation was not associated with functional improvement. CONCLUSION: A large proportion of older patients discontinue adjuvant endocrine treatment within 2 years after initiation, but geriatric characteristics are not predictive of early discontinuation of treatment. Discontinuation of adjuvant endocrine therapy did not positively affect QoL and functional status, which implies that the observed poorer QoL in this group is probably not caused by adverse effects of endocrine therapy.

Geriatric assessment and treatment outcomes in a Dutch cohort of older patients with potentially curable esophageal cancer.

BACKGROUND: Patients with potentially curable esophageal cancer can be treated with neo-adjuvant chemoradiotherapy followed by surgery or definitive chemoradiotherapy with curative intent. For frail older patients choosing the appropriate oncological treatment can be difficult, and data on geriatric deficits as determinants of treatment outcomes are not yet available. OBJECTIVES: To describe the prevalence of geriatric deficits and to study their association with treatment discontinuation and mortality in older patients with potentially curable esophageal cancer. MATERIAL AND METHODS: A cohort study was conducted in a Dutch tertiary care hospital including patients aged ≥70 years with primary stage I-IVA esophageal cancer. Geriatric screening and assessment data were collected. Outcomes were treatment discontinuation and one year all-cause mortality. RESULTS: In total, 138 patients with curable esophageal cancer were included. Mean age was 76.1 years (standard deviation 4.7), 54% had clinical stage III and 24% stage IVA disease. Most patients received neo-adjuvant chemoradiotherapy and surgery (41%), 32% definitive chemoradiotherapy and 22% palliative radiotherapy. Overall, one year all-cause mortality was 36%. Geriatric screening and assessment was performed in 94 out of 138 patients, of which 60% was malnourished, 20% dependent in Instrumental Activities of Daily Living (IADL) and 52% was frail. Malnutrition was associated with higher mortality risk (Hazard Ratio, 3.2; 95% Confidence Interval, 1.3-7.7)) independent of age, sex and tumor stage. Seventy-six out of 94 patients were treated with chemoradiotherapy, of which 23% discontinued treatment. Patients with IADL dependency and Charlson Comorbidity Index ≥1 discontinued treatment more often. CONCLUSION: All-cause mortality within one year was high, irrespective of treatment modality. Treatment discontinuation rate was high, especially in patients treated with definitive chemoradiotherapy. Geriatric assessment associates with outcomes in older patients with esophageal cancer and may inform treatment decisions and optimization in future patients, but more research is needed to establish its predictive value. Trial registration: The study is retrospectively registered at the Netherlands Trial Register (NTR), trial number NL8107. Date of registration: 22-10-2019.

Low preoperative skeletal muscle density is predictive for negative postoperative outcomes in older women with ovarian cancer.

OBJECTIVE: To determine the predictive value of lumbar skeletal muscle mass and density for postoperative outcomes in older women with advanced stage ovarian cancer. METHODS: A multicenter, retrospective cohort study was performed in women ≥ 70 years old receiving surgery for primary, advanced stage ovarian cancer. Skeletal muscle mass and density were assessed in axial CT slices on level L3. Low skeletal muscle mass was defined as skeletal muscle index < 38.50 cm2/m2. Low skeletal muscle density was defined as one standard deviation below the mean (muscle attenuation < 22.55 Hounsfield Units). The primary outcome was any postoperative complication ≤ 30 days after surgery. Secondary outcomes included severe complications, infections, delirium, prolonged hospital stay, discharge destination, discontinuation of adjuvant chemotherapy and mortality. RESULTS: In analysis of 213 patients, preoperative low skeletal muscle density was associated with postoperative complications ≤ 30 days after surgery (Odds Ratio (OR) 2.83; 95% Confidence Interval (CI) 1.41-5.67), severe complications (OR 3.01; 95%CI 1.09-8.33), infectious complications (OR 2.79; 95%CI 1.30-5.99) and discharge to a care facility (OR 3.04; 95%CI 1.16-7.93). Preoperative low skeletal muscle mass was only associated with infectious complications (OR 2.32; 95%CI 1.09-4.92). In a multivariable model, low skeletal muscle density was of added predictive value for postoperative complications (OR 2.57; 95%CI 1.21-5.45) to the strongest existing predictor functional impairment (KATZ-ADL ≥ 2). CONCLUSION: Low skeletal muscle density, as a proxy of muscle quality, is associated with poor postoperative outcomes in older patients with advanced stage ovarian cancer. These findings can contribute to postoperative risk assessment and clinical decision making.

Frailty is associated with in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands: the COVID-OLD study.

BACKGROUND: During the first wave of the coronavirus disease 2019 (COVID-19) pandemic, older patients had an increased risk of hospitalisation and death. Reports on the association of frailty with poor outcome have been conflicting. OBJECTIVE: The aim of the present study was to investigate the independent association between frailty and in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands. METHODS: This was a multicentre retrospective cohort study in 15 hospitals in the Netherlands, including all patients aged ≥70 years, who were hospitalised with clinically confirmed COVID-19 between February and May 2020. Data were collected on demographics, co-morbidity, disease severity and Clinical Frailty Scale (CFS). Primary outcome was in-hospital mortality. RESULTS: A total of 1,376 patients were included (median age 78 years (interquartile range 74-84), 60% male). In total, 499 (38%) patients died during hospital admission. Parameters indicating presence of frailty (CFS 6-9) were associated with more co-morbidities, shorter symptom duration upon presentation (median 4 versus 7 days), lower oxygen demand and lower levels of C-reactive protein. In multivariable analyses, the CFS was independently associated with in-hospital mortality: compared with patients with CFS 1-3, patients with CFS 4-5 had a two times higher risk (odds ratio (OR) 2.0 (95% confidence interval (CI) 1.3-3.0)) and patients with CFS 6-9 had a three times higher risk of in-hospital mortality (OR 2.8 (95% CI 1.8-4.3)). CONCLUSIONS: The in-hospital mortality of older hospitalised COVID-19 patients in the Netherlands was 38%. Frailty was independently associated with higher in-hospital mortality, even though COVID-19 patients with frailty presented earlier to the hospital with less severe symptoms.

Design and rationale of a routine clinical care pathway and prospective cohort study in older patients needing intensive treatment.

BACKGROUND: Treatment decisions concerning older patients can be very challenging and individualised treatment plans are often required in this very heterogeneous group. In 2015 we have implemented a routine clinical care pathway for older patients in need of intensive treatment, including a comprehensive geriatric assessment (CGA) that was used to support clinical decision making. An ongoing prospective cohort study, the Triaging Elderly Needing Treatment (TENT) study, has also been initiated in 2016 for participants in this clinical care pathway, to study associations between geriatric characteristics and outcomes of treatment that are relevant to older patients. The aim of this paper is to describe the implementation and rationale of the routine clinical care pathway and design of the TENT study. METHODS: A routine clinical care pathway has been designed and implemented in multiple hospitals in the Netherlands. Patients aged ≥70 years who are candidates for intensive treatments, such as chemotherapy, (chemo-)radiation therapy or major surgery, undergo frailty screening based on the Geriatric 8 (G-8) questionnaire and the Six-Item Cognitive Impairment Test (6CIT). If screening reveals potential frailty, a CGA is performed. All patients are invited to participate in the TENT study. Clinical data and blood samples for biomarker studies are collected at baseline. During follow-up, information about treatment complications, hospitalisations, functional decline, quality of life and mortality is collected. The primary outcome is the composite endpoint of functional decline or mortality at 1 year. DISCUSSION: Implementation of a routine clinical care pathway for older patients in need of intensive treatment provides the opportunity to study associations between determinants of frailty and outcomes of treatment. Results of the TENT study will support individualised treatment for future patients. TRIAL REGISTRATION: The study is retrospectively registered at the Netherlands Trial Register (NTR), trial number NL8107 . Date of registration: 22-10-2019.

The G8 frailty screening tool and the decision-making process in older breast cancer patients.

OBJECTIVE: To assess the decision-making process in fit and frail older breast cancer patients. METHODS: Breast cancer patients aged ≥70 years who completed the G8 frailty screening tool (G8) were included in this retrospective study. Socio-demographic and clinical characteristics were collected, as well as information from geriatric assessment (GA). Treatment decisions were compared with national guidelines. RESULTS: Of 177 patients, 85 patients were considered fit by the G8 (G8-fit) and 92 patients frail (G8-frail). All G8-fit and 53 G8-frail were proposed for surgery. GA was performed in 34 patients (9 G8-fit; 25 G8-frail) of whom 16 (2 G8-fit;14 G8-frail) were considered frail (GA-frail). 28 out of these 34 patients were considered fit for surgery (including 11 GA-frail); their impairments were unlikely to interfere with surgery or life expectancy. Reasons for adjusting treatment were physical/cognitive condition and patient preference. Ultimately, 123 patients underwent surgery in accordance with guidelines (81 G8-fit;42 G8-frail, p < 0.001). Survival was reduced in G8-frail compared to G8-fit (p = 0.001), but G8 lost its association with mortality in multivariable survival analysis. Among patients undergoing surgery, no difference in mortality was seen between G8-fit and G8-frail (p = 0.996). CONCLUSION: The G8 is associated with treatment decisions and did not affect survival in patients undergoing surgery. In the decision-making process, the G8 may help and estimates the need for adaptive care.

The Effect of A Geriatric Assessment on Treatment Decisions for Patients with Lung Cancer.

BACKGROUND: Decision-making for older patients with lung cancer can be complex and challenging. A geriatric assessment (GA) may be helpful and is increasingly being used since 2005 when SIOG advised to incorporate this in standard work-up for the elderly with cancer. Our aim was to evaluate the value of a geriatric assessment in decision-making for patients with lung cancer. METHODS: Between January 2014 and April 2016, data on patients with lung cancer from two teaching hospitals in the Netherlands were entered in a prospective database. Outcome of geriatric assessment, non-oncologic interventions, and suggested adaptations of oncologic treatment proposals were evaluated. RESULTS: 83 patients (median age 79 years) were analyzed with a geriatric assessment, of which 59% were treated with a curative intent. Half of the patients were classified as ECOG PS 0 or 1. The majority of the patients (78%) suffered from geriatric impairments and 43% (n = 35) of the patients suffered from three or more geriatric impairments (out of eight analyzed domains). Nutritional status was most frequently impaired (52%). Previously undiagnosed impairments were identified in 58% of the patients, and non-oncologic interventions were advised for 43%. For 33% of patients, adaptations of the oncologic treatment were proposed. Patients with higher number of geriatric impairments more often were advised a reduced or less intensive treatment (p < 0.001). CONCLUSION: A geriatric assessment uncovers previously unknown health impairments and provides important guidance for tailored treatment decisions in patients with lung cancer. More research on GA-stratified treatment decisions is needed.

Lung Cancer in the Oldest Old: A Nation-Wide Study in The Netherlands.

INTRODUCTION: An important step in improving research and care for the oldest patients with lung cancer is analyzing current data regarding diagnostic work-up, treatment choices, and survival. METHODS: We analyzed data on lung cancer from the Netherlands Cancer Registry (NCR-IKNL) regarding diagnostic work-up, treatment, and survival in different age categories; the oldest old (≥85 years of age) versus those aged 71-84 (elderly) and those aged ≤70 years (younger patients). RESULTS: 47,951 patients were included in the 2010-2014 NCR database. 2196 (5%) patients were aged ≥85 years. Histological diagnosis was obtained significantly less often in the oldest old (38%, p < 0.001), and less standard treatment regimen was given (8%, p < 0.001) compared to elderly and younger patients. 67% of the oldest old received best supportive care only versus 38% of the elderly and 20% of the younger patients (p < 0.001). For the oldest old receiving standard treatment, survival rates were similar in comparison with the elderly patients. In the oldest old, no survival differences were found when comparing standard or adjusted regimens for stage I and IV NSCLC; for stage III, oldest old receiving standard treatment had longer survival. No oldest old patients with stage II received standard treatment. CONCLUSION: Clinicians make limited use of diagnostics and invasive treatment in the oldest old; however, selected oldest old patients experienced similar survival rates as the elderly when receiving some form of anticancer therapy (standard or adjusted). More research is needed to further develop individualized treatment algorithms.

[Evidence based tailoring of cancer care for older patients]. / Evidence-based maatwerk voor ouderen met kanker.

Cancer is a disease that disproportionately affects the elderly. Evidence-based treatment is the golden standard of current medical care, and this is also true for older cancer patients. In developing guidelines, all available evidence is collected, appraised and summarized. Subsequent recommendations are then translate to criteria used to judge the quality of care. The heterogeneity of the elderly population requires tailoring of care, which is the opposite of the often strictly formulated treatment recommendations in guidelines and protocols. This paper discusses several issues regarding evidence based treatment versus tailored care for older cancer patients.

Physical performance measures for predicting outcome in cancer patients: a systematic review.

BACKGROUND: Decision making regarding cancer treatment is challenging and there is a need for clinical parameters that can guide these decisions. As physical performance appears to be a reflection of health status, the aim of this systematic review is to assess whether physical performance tests (PPTs) are predictive of the clinical outcome and treatment tolerance in cancer patients. METHODS: A literature search was conducted on 2 April 2015 in the electronic databases Medline and Embase to identify studies focusing on the association between objectively measured PPTs and outcome. No limitations in language or publication dates were applied. RESULTS: The search retrieved 9680 articles, 16 publications were included involving 4187 patients with various cancer types and different treatments. Reported median or mean age varied from 58 to 78 years. Nine studies used the Timed Up & Go (TUG) test, five the Short Physical Performance Battery (SPPB) and five studies focused on gait speed. Poorer TUG, SPPB and gait speed outcome were associated with decreased survival. TUG, SPPB and gait speed were also associated with treatment-related complications. Furthermore, two studies reported an association between poorer TUG and SPPB outcome with higher rates of functional decline. CONCLUSION: PPTs appear to show a significant correlation with survival and these tests could be used as a prognostic tool, particular for older adult patients. A less explicit correlation for treatment-related complications and functional decline was also found. To optimize decision making, future research should focus on developing and validating individualized treatment algorithms that incorporate PPTs in addition to cancer- and treatment-related variables.

Patient-Centered Outcome Measures in Lung Cancer Trials.

BACKGROUND: Scientific communities focusing on cancer research have urged for the development of trials that address patient-centered outcome measures instead of solely focusing on cancer as a disease-centered process. This is important for a patient with lung cancer because of the rapid course of disease and generally poor prognosis. We set out to determine the characteristics and study objectives of the current clinical trials in pulmonary malignancies. METHODS: The United States National Institutes of Health clinical trial registry was searched on April 23rd 2015, for currently recruiting phase I, II, or III clinical trials in lung cancer. Trial characteristics and study objectives were extracted from the registry website. RESULTS: Of the 419 clinical trials included in this review, patient-centered outcome measures are investigated in a minority of the trials. Outcome measures as quality of life, functional capacity, and health care utilization are included in a small number of trials (20, 4, and 2 % respectively). Treatment completion is included in 1 % of the trials. Research goals are most frequently toxicity (78 %) and progression-free survival (76 %). CONCLUSION: Patient-centered outcome measures are included in a minority of the currently recruiting clinical trials in pulmonary malignancies. If we do not investigate these outcome measures, it is not possible to increase our knowledge of the optimal treatment, as this should aim to optimize the patient's wellbeing as well as the course of disease. One option could be to incorporate combinations of patient- and disease-centered endpoints, for instance by using overall treatment utility or quality-adjusted outcome measures.

Selection of Patients in Ongoing Clinical Trials on Lung Cancer.

BACKGROUND: Lung cancer is predominantly a disease of the elderly: half of all newly diagnosed patients are over 70 years old. Older patients and those with comorbidities are underrepresented in clinical trials; scientific communities have addressed this issue since the end of the 20th century. We set out to determine the characteristics of the selection of patients in lung cancer trials that are currently recruiting. METHODS: We searched The United States National Institutes of Health (NIH) clinical trial registry ( www.clinicaltrials.gov ) on April 23, 2015 for currently recruiting phase I, II, or III clinical trials in lung cancer. Trial characteristics and study objectives were extracted from the registry website. RESULTS: Of the 419 trails selected in this overview, 88 % explicitly or implicitly excluded elderly patients. Patients were excluded based on stringent organ selection in 76 % of the trials, based on performance status (57 %) and based on age (13 %). The median number of placed restrictions per trial was seven. In the 2 % of the trials that were exclusively designed for elderly patients only fit patients were included. CONCLUSION: In this overview of current lung cancer trials registered in the NIH clinical trial registry, we found that elderly patients and those with comorbidities are often excluded from participation in clinical trials. Therefore, it is difficult for physicians and their frail patients to properly evaluate the efficacy and safety of current treatment options. More research that includes the elderly and those with comorbidities is urgently needed.