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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., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Vitamin D supplementation has been suggested for many diseases and symptoms that are frequent in older people: loss of bone mineral density, falls, loss of muscle mass, infections (including COVID-19) and mortality. In observational studies, vitamin D concentration has been associated with many poor outcomes, but in most Randomized Controlled Trials, there is no beneficial effect of vitamin D supplementation on these outcomes, except for bone mineral density. An alternative explanation of the observed association may be 'confounding': older people with poor mobility have lower vitamin D, and irrespective of that also have poor outcomes. The recent COVIT-TRIAL seems to suggest there is benefit of high dose vitamin D supplementation compared to low dose on mortality in older people with COVID-19, but on closer methodological look this conclusion does not hold. Clinical guidelines rightly do not advise vitamin D supplementation for a whole range of diseases, including COVID-19.

In addition to frailty, two novel concepts have been introduced in the field of geriatrics to capture the heterogeneous ageing process: the first is intrinsic capacity, which uses a community-based, holistic approach and is propagated by the World Health Organization (WHO); and the second is resilience, which provides a more dynamic perspective on the individual's reserves, injury and recovery. While both concepts are linked to frailty, with all three focusing on reserves in relation to ageing, each approaches this issue from a different point of view. In this paper, we will compare and contrast these three concepts - frailty, intrinsic capacity and resilience - and assess their relevance to future geriatric oncology research as well as daily clinical practice., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Vulvar cancer is a disease that mainly affects older women. Frailty is an important predictor of outcomes and geriatric assessment can help tailor treatment decisions and improve outcomes. This study aims to assess the prevalence of frailty in older women with vulvar cancer, and how it relates to integrated geriatric care and treatment according to the oncological guidelines., Materials and Methods: A single-center cohort study was performed, among patients 70 years and older, who were diagnosed with vulvar cancer at Leiden University Medical Center, between January 2012 and May 2020. Data on geriatric assessment, treatment decision-making and treatment-related outcomes were collected., Results: Our study included 114 patients. Mean age was 79.7 years, and 52 patients (45.6%) were frail. Of the frail patients, 42.0% were referred to a geriatrician. In eight of these cases, the geriatrician was actively involved in weighing the benefit and harm of standard oncological treatment versus de-escalated treatment. Frailty, higher age, impairment in the somatic domain, cognitive impairment, and functional dependency were associated with referral to a geriatrician and with active involvement of a geriatrician in decision making. In 26 of frail patients (50.0%) oncological treatment was de-escalated. Frailty, higher age, impairment in the somatic domain, cognitive impairment, and functional dependency were associated with de-escalation of treatment. De-escalated treatment did not compromise survival., Discussion: Frailty is prevalent among older women with vulvar cancer and is associated with referral to a geriatrician and de-escalation of oncological treatment. While this reflects that it is deemed important to tailor treatment decision for frail patients, most frail patients are not routinely evaluated by a geriatrician. Further multidisciplinary collaboration and research is necessary to optimize tailored treatment decisions for this patient group., Competing Interests: Declaration of Competing Interest Nothing to disclose., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Around 45% of patients with melanoma are older than 65 years. In recent years, immunotherapy has proven very effective for metastasised melanoma. The aim of this study was to investigate the time trends in treatment strategies and survival in older versus younger patients with synchronous metastasised melanoma. We included all patients diagnosed between 2000 and 2019 from the Netherlands cancer registry. We analysed changes in first-line systemic treatment using multivariable logistic regression models, stratified by age (<65, 65−75, and ≥75). Changes in overall survival were studied using multivariable Cox regression analysis. A total of 2967 patients were included. Immunotherapy prescription increased significantly over time for all age groups (<65 years: 11.8% to 64.9%, p < 0.001; 65−75 years: 0% to 68.6%, p < 0.001; >75 years: 0% to 39.5%, p < 0.001). In multivariable analyses, overall survival improved for patients aged <65 and 65−75 (HR 0.96, 95% CI 0.92−1.00 and HR 0.95, 95% CI 0.89−1.00, respectively), but not in patients over 75 (HR 0.98, 95% CI 0.91−1.05). In conclusion, overall survival has improved in patients with synchronous metastasised melanoma aged <75 years, but not in patients aged 75 years or older. This might be explained by lower prescription rates of immunotherapy in this age group.

Introduction: To compare the real-world safety profile of programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) inhibitors between younger and older patients., Materials and Methods: All patients receiving pembrolizumab, nivolumab, atezolizumab or durvalumab between September 2016 and September 2019 at Haga Teaching Hospital, The Hague, The Netherlands were included in this retrospective study. Immune-related adverse drug reactions (irADRs) were manually retrieved from the electronic patient files. The cumulative incidence of irADRs were compared between younger (<65 years) and older (≥65 years) patients using a Pearsons Chi-square test., Results: We identified 217 patients who were treated with at least one dose of PD-(L)1 inhibitor. 58% were 65 years or older at the start of immunotherapy. 183 patients (84.3%) received monotherapy PD-(L)1 inhibitors and 34 (15.7%) received chemo-immunotherapy. A total of 278 irADRs were registered. Cutaneous irADRs (53.9%), thyroid gland disorders (20.3%), and non-infectious diarrhoea/colitis (17.5%) were the most frequently reported irADRs. The majority of the irADRs were mild to moderate and no fatal irADRs were observed. 61 (21.9%) of the irADRs needed systemic treatment, of which 19 (6.8%) required treatment with corticosteroids. 18 irADRs (6.5%) were severe and resulted in hospitalisation. The cumulative incidence of cutaneous irADRs was different between the age groups: 45.7% of the patients <65 years and in 60.0% of the patients ≥65 years (p = 0.036). No statistical difference was found in the cumulative incidence of other irADRs between the two age groups., Discussion: Advanced age is not associated with immune-related adverse drug reactions of PD-1 and PD-L1 inhibitors., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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., (© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: For clinical decision making it is important to identify patients at risk for adverse outcomes after colorectal cancer (CRC) surgery, especially in the older population. Because the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) surgical risk calculator is potentially useful in clinical practice, we performed an external validation in a Dutch multicenter cohort of patients ≥70 years undergoing elective non-metastatic CRC surgery., Methods: We compared the ACS NSQIP calculator mean predicted risk to the overall observed rate of anastomotic leakage, return to operation room, pneumonia, discharge not to home, and readmission in our cohort using a one-sample Z-test. Calibration plots and receiver operating characteristic (ROC) curves were used to determine the calculator's performance., Results: Six hundred eighty-two patients were included. Median age was 76.2 years. The ACS NSQIP calculator accurately predicted the overall readmission rate (predicted: 8.6% vs. observed: 7.8%, p = 0.456), overestimated the rate of discharge not to home (predicted:11.2% vs. observed: 7.0% p = 0.005) and underestimated the observed rate of all other outcomes. The calibration plots showed poor calibration for all outcomes. The ROC-curve showed an area under the curve (AUC) of 0.75 (95% confidence interval [CI] 0.67-0.83) for pneumonia and 0.70 (0.62-0.78) for discharge not to home. The AUC for all other outcomes was poor., Conclusions: The ACS NSQIP surgical risk calculator had a poor individual risk prediction (calibration) for all outcomes and only a fair discriminative ability (discrimination) to predict pneumonia and discharge not to home. The calculator might be considered to identify patients at high risk of pneumonia and discharge not to home to initiate additional preoperative interventions., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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., (© 2022. The Author(s).)

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.

Background: Understanding what information patients want and need is an important step in optimizing care. Therefore, we set out to collect all available evidence about the information that is most important to older patients with a new cancer diagnosis and whether or not these information needs are sufficiently addressed., Method: A systematic literature review of Embase and Medline., Results: We included eighteen studies addressing the importance of a range of information topics and studies addressing the sufficiency of information provided. On a scale from 1 to 10, patients ranked information about prognosis and the chance of cure as the most important category (median ranking 10, interquartile range (IQR) 8-10), followed by information on cancer itself (median 9, IQR 5.5-9), and treatment options (median 8, IQR 8-9). Information on side-effects of treatment (median 7, IQR 6-8), and practicalities (median 6, IQR 5-7.5) were also considered important. Patients rated information about the practicalities of treatment as the most insufficiently addressed (median 9.5), followed by self-care at home (median 9), and information about prognosis and side-effects (median 8 for both)., Conclusion: This systematic review demonstrates that information provision about the cancer itself and about treatment options is generally satisfactory to patients, while information about prognosis, practicalities of treatment and self-care at home could be improved. However, there is significant heterogeneity among older patients regarding which information is most important to them, thus requiring an ongoing dialogue between patients and health care providers about which information is most needed at any given time., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Polypharmacy is common in older adults with cancer and deprescribing potentially inappropriate medications becomes very relevant when life expectancy decreases due to metastatic disease. Especially preventive medications may no longer be beneficial, because they may decrease quality of life and reduction in morbidity and mortality may be futile. Although deprescribing of preventive medication is common in the last period of life, it is still unusual during active cancer treatment for advanced disease, although life expectancy is often limited to less than 1 to 2 years in that stage. We performed a systematic search of the literature in Pubmed and Embase on the discontinuation of commonly utilized groups of preventive medication and evaluated the evidence of potential benefits and harms in patients aged 65 years or older with cancer and a limited life expectancy (LLE). From 21 included studies, it can be concluded that deprescribing lipid lowering drugs, antihypertensive drugs, osteoporosis drugs and antihyperglycemic drugs is feasible in a considerable part of patients with a LLE. Discontinuation may be performed safely, without the occurrence of serious adverse events or decrease of survival. The only study that addressed quality of life after deprescribing showed that discontinuation of statins improves quality of life in patients with a LLE. Recurrence of symptoms requiring reintroduction occurred in 0-13% of patients on antihyperglycemic treatment and 8-60% of patients using antihypertensive drugs. In order to reduce pill burden and futile treatment clinicians should discuss deprescribing of preventive medication with older patients with advanced cancer and a LLE.

Introduction: In addition to classical endpoints such as survival and complication rates, other outcomes such as quality of life and functional status are increasingly recognized as important endpoints, especially for elderly patients. However, little is known about the long-term effect of surgery with regard to these other outcomes. Our aim is to investigate the functional status and self-reported health status of patients ≥ 70 years one year after surgery for head and neck cancer., Methods: We present one-year follow-up data of patients ≥ 70 year who underwent surgery for HNC. During an interview by telephone, functional status was evaluated by using the Katz-15 Index of Independence questionnaire including six items covering basic Activities of Daily Living (ADL) and nine items covering Instrumental Activities of Daily Living (IADL). Measurements were compared with those obtained preoperatively., Results: In total, 126 patients were included and eventually we collected follow-up data of 68 patients. There was a statistically significant decrease in functional status on the total Katz-15 and on the IADL questionnaire scores one year after surgery (mean 1.34 versus 2.42,p-value 0.00 and mean 1.21 versus 1.94,p-value 0.00). There was no significant change concerning ADL dependence (p-value 0.18) and cognitive status (p-value 0.11). The self-reported health status improved postoperatively, although not statistically significantly so (mean 67.36 versus 71.25,p-value 0.12)., Conclusion: Approximately-one year after surgery for HNC, there is a significant decline in functional status indicating a higher level of dependency., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The COVID-19 pandemic pressurised healthcare with increased shortage of care. This resulted in an increase of awareness for code status documentation (ie, whether limitations to specific life-sustaining treatments are in place), both in the medical field and in public media. However, it is unknown whether the increased awareness changed the prevalence and content of code status documentation for COVID-19 patients. We aim to describe differences in code status documentation between infectious patients before the pandemic and COVID-19 patients., Setting: University Medical Centre of Utrecht, a tertiary care teaching academic hospital in the Netherlands., Participants: A total of 1715 patients were included, 129 in the COVID-19 cohort (a cohort of COVID-19 patients, admitted from March 2020 to June 2020) and 1586 in the pre-COVID-19 cohort (a cohort of patients with (suspected) infections admitted between September 2016 to September 2018)., Primary and Secondary Outcome Measures: We described frequency of code status documentation, frequency of discussion of this code status with patient and/or family, and content of code status., Results: Frequencies of code status documentation (69.8% vs 72.7%, respectively) and discussion (75.6% vs 73.3%, respectively) were similar in both cohorts. More patients in the COVID-19 cohort than in the before COVID-19 cohort had any treatment limitation as opposed to full code (40% vs 25%). Within the treatment limitations, 'no intensive care admission' (81% vs 51%) and 'no intubation' (69% vs 40%) were more frequently documented in the COVID-19 cohort. A smaller difference was seen in 'other limitation' (17% vs 9%), while 'no resuscitation' (96% vs 92%) was comparable between both periods., Conclusion: We observed no difference in the frequency of code status documentation or discussion in COVID-19 patients opposed to a pre-COVID-19 cohort. However, treatment limitations were more prevalent in patients with COVID-19, especially 'no intubation' and 'no intensive care admission'., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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 cm 2 /m 2 . 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., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction Older patients have an increased risk of morbidity and mortality after colorectal cancer (CRC) surgery. Existing CRC surgical prediction models have not incorporated geriatric predictors, limiting applicability for preoperative decision-making. The objective was to develop and internally validate a predictive model based on preoperative predictors, including geriatric characteristics, for severe postoperative complications after elective surgery for stage I-III CRC in patients ≥70 years., Patients and Methods: A prospectively collected database contained 1088 consecutive patients from five Dutch hospitals (2014-2017) with 171 severe complications (16%). The least absolute shrinkage and selection operator (LASSO) method was used for predictor selection and prediction model building. Internal validation was done using bootstrapping., Results: A geriatric model that included gender, previous DVT or pulmonary embolism, COPD/asthma/emphysema, rectal cancer, the use of a mobility aid, ADL assistance, previous delirium and polypharmacy showed satisfactory discrimination with an AUC of 0.69 (95% CI 0.73-0.64); the AUC for the optimism corrected model was 0.65. Based on these predictors, the eight-item colorectal geriatric model (GerCRC) was developed., Conclusion: The GerCRC is the first prediction model specifically developed for older patients expected to undergo CRC surgery. Combining tumour- and patient-specific predictors, including geriatric predictors, improves outcome prediction in the heterogeneous older population.

Background: Previous trials suggest no differences in immunotherapy treatment between older and younger patients, but mainly young patients with a good performance status were included. The aim of this study was to describe the treatment patterns and outcomes of "real-world" older patients with metastatic melanoma and to identify predictors of outcome., Methods: We included patients aged ≥65 years with metastatic melanoma from the Dutch Melanoma Treatment Registry. We described the reasons for hospital admissions and treatment discontinuation. Additionally, we assessed predictors of toxicity and response using logistic regression models and survival using Cox regression models., Results: We included 2216 patients. Grade ≥3 toxicity was not associated with age, comorbidities or WHO status. Patients aged ≥75 discontinued treatment due to toxicity more often, resulting in fewer treatment cycles. Response rates were similar to previous trials (40.3% and 43.6% in patients aged 65-75 and ≥75, respectively, for anti-PD1 treatment) and did not decrease with age or comorbidity. Melanoma-specific survival was not affected by age or comorbidity., Conclusion: Response rates and toxicity outcomes of checkpoint inhibitors did not change with increasing age or comorbidity. However, the impact of grade I-II toxicity on quality of life deserves further study as older patients discontinue treatment more frequently.

Background: The Geriatric 8 (G8) has proven to be one of the most sensitive frailty-screening tools for older patients with cancer undergoing systemic treatment. In this study we validated whether the G8 is also suitable for identifying impairments in their comprehensive geriatric assessment (CGA) in older patients with cancer undergoing surgery. Thereby, we investigated the differences in postoperative outcomes between the fit and frail patients classified by the G8., Methods: Patients ≥70 years with a surgery indication because of a (suspected) malignant disease were prospectively enrolled. In all patients, a CGA was performed. The G8 results were assessed in parallel. The diagnostic value of the G8 was determined by comparing the result with the CGA as a reference test. Deficits in CGA was defined as ≥ two impairments of the CGA. Postoperative complications were retrospectively obtained from the medical record and compared between the fit and frail patients., Results: In total, 143 patients were enrolled. The sensitivity, specificity, and negative predictive value of the G8 were 82% (95% CI 70-91), 63% (95% CI 52-73), and 85% (95% CI 75-91). In the patients with an impaired G8, a significantly prolonged hospital stay, higher rate of delirium, and higher 1-year mortality rate were seen., Conclusion: The G8 is a simple and useful screening tool for identifying deficits in CGA in older patients with cancer requiring surgery. Second, we concluded that patients with an impaired G8 are more at risk for a complicated recovery from surgery., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The number of older patients with breast cancer has increased due to the aging of the general population. The use of a geriatric assessment in this population has been advocated in many studies and guidelines as it can be used to identify high risk populations for early mortality and toxicity. Additionally, geriatric parameters could predict relevant outcome measures. This systematic review summarizes all available evidence on predictive factors for various outcomes (disease-related and survival, toxicity, and patient-reported outcomes), with a special focus on geriatric parameters and patient-reported outcomes, in older patients with breast cancer. Studies were identified through systematic review of the literature published up to September 1st 2019 in the PubMed database and EMBASe. A total of 173 studies were included. Most studies investigated disease-related and survival outcomes (n = 123, 71%). Toxicity was investigated in 40 studies (23%) and a mere 15% (n = 26) investigated patient-reported outcomes. Various measures that can be derived from a geriatric assessment were predictive for survival endpoints. Furthermore, geriatric parameters were among the most frequently found predictors for toxicity and patient-reported outcomes. In conclusion, this study shows that geriatric parameters can predict survival, toxicity, and patient-reported outcomes in older patients with breast cancer. These findings can be used in daily clinical practice to identify patients at risk of early mortality, high risk of treatment toxicity or poor functional outcome after treatment. A minority of studies used relevant outcome measures for older patients, showing the need for studies that are tailored to the older population., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Shared decision-making in cancer care, where we move away from the paternalistic "the doctor knows best" attitude to involving the patient in decisions regarding her or his health, is now universally accepted in western societies. However, in many situations this is easier said than done. For instance, if the interaction with the patient is not performed in a skillful manner, shared decision-making can make the patient feel unsafe - shouldn't the specialist know how to treat a serious disease such as cancer? Why would the doctor ask the patient about this? In other cases, what the patient wants in unrealistic, for example a severely frail patient aged 85 years with more than one life-limiting comorbidity who is diagnosed with an advanced cancer and has a goal of living to be at least 100 years. And what does a patient with advanced dementia want in the context of a cancer disease? In this perspectives piece, we will describe different scenarios that may arise within geriatric oncology and shared decision-making, make recommendations about how to handle such situations, and provide some food for thought., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Patients with head and neck cancer (HNC) have a risk of sarcopenia which is associated with adverse health outcomes. Frailty is also associated with adverse outcomes and is diagnosed by a comprehensive geriatric assessment (CGA). Because a CGA is time-consuming and not all patients benefit from it, frailty screening questionnaires are used to select patients for CGA. Sarcopenia measurement may be a biomarker for frailty. Our objective was to examine the association between sarcopenia and a frailty screening questionnaire., Materials and Methods: In this single-center retrospective study, 150 patients (≥ 60-years old) with HNC were reviewed. Sarcopenia was defined as the combination of reduced handgrip strength and loss of skeletal muscle mass, calculated as skeletal muscle index (SMI), according to the EWGSOP-criteria. Frailty screening was performed using the Geriatrics 8 (G8) questionnaire., Results: The 150 patients included 101 men and 49 women. Frail patients were more likely to be sarcopenic at diagnosis. G8 frailty score showed a significant though weak correlation with SMI. Univariate regression analysis with frailty as a dependent variable distinguished comorbidity score, handgrip strength, SMI, and sarcopenia as significant. These variables were subjected to a multivariate analysis in which comorbidity score and SMI remained significant., Conclusion: There is an association between sarcopenia and the G8 frailty screening questionnaire. Therefore, sarcopenia measurement could be interchangeable with the G8 frailty screening questionnaire. Further research should compare the gold standard for frailty, i.e. CGA, with sarcopenia., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.

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., (© 2020 John Wiley & Sons Ltd.)

Background: Malnourishment is commonly seen in ageing, cancer and many chronic conditions, and is associated with poorer prognosis., Aim: We set out to collect all currently available evidence on the association between nutritional status assessed with a validated screening tool and prognosis or course of treatment in older patients with cancer, and on the benefit of nutritional interventions in improving these outcomes., Methods: A systematic search in MEDLINE and EMBASE., Results: We included 71 studies on the association between nutritional status and outcome in (older) patients with cancer and 17 studies on the benefit of nutritional interventions in improving outcomes in this patient population. There is a significant association between nutritional status and increased intermediate- and long-term mortality (hazard ratio 1.87 (95% confidence interval 1.62-2.17). Those with poorer nutritional status were less likely to complete oncologic treatment according to plan and had higher health care consumption. Benefit of dietary interventions was limited although dietary counselling may lead to improved quality of life while nutritional support may lead to a decrease in post-operative complication rates., Conclusion: Nutritional status is associated with poorer survival, decreased treatment completion and higher health care consumption and nutritional interventions are only able to negate these negatives outcome to a very limited degree., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: An increasing number of patients with Colorectal Cancer (CRC) is 65 years or older. We aimed to systematically review existing clinical prediction models for postoperative outcomes of CRC surgery, study their performance in older patients and assess their potential for preoperative decision making., Methods: A systematic search in Pubmed and Embase for original studies of clinical prediction models for outcomes of CRC surgery. Bias and relevance for preoperative decision making with older patients were assessed using the CHARMS guidelines., Results: 26 prediction models from 25 publications were included. The average age of included patients ranged from 61 to 76. Two models were exclusively developed for 65 and older. Common outcomes were mortality (n = 10), anastomotic leakage (n = 7) and surgical site infections (n = 3). No prediction models for quality of life or physical functioning were identified. Age, gender and ASA score were common predictors; 12 studies included intraoperative predictors. For the majority of the models, bias for model development and performance was considered moderate to high., Conclusions: Prediction models are available that address mortality and surgical complications after CRC surgery. Most models suffer from methodological limitations, and their performance for older patients is uncertain. Models that contain intraoperative predictors are of limited use for preoperative decision making. Future research should address the predictive value of geriatric characteristics to improve the performance of prediction models for older patients., Competing Interests: Declaration of Competing Interest All authors declare that there is no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Geriatric assessment (GA) is an appropriate method for identifying frailty in older patients with cancer, but a shorter instrument may be easier to use in clinical practice. Clinical judgment is always available and requires no investments in time or resources. The purpose of this study was to assess correlations between clinical judgment for frailty of the cancer specialist, the general practitioner and patient's self-assessment, and the correlation between clinical judgment and GA., Methods: This was a dual-center inception cohort study of patients with cancer aged ≥70 years starting curative or first-line palliative chemotherapy. GA included the following domains: (instrumental) activities of daily living, nutrition, mobility, cognition, mood, and polypharmacy. Clinical judgment for frailty was rated on a scale from 0 to 10 (0 = not frail, 10 = frail). Correlation was tested using Kendall's tau-b correlation coefficient., Results: Of all 55 patients, 76% had ≥2 geriatric impairments. Median clinical judgment frailty score was 3 (range 1-10 for cancer specialist and patient and range 0-10 for general practitioner) and did not vary much according to the number of impaired geriatric domains (ranging from 2 for 0-1 impaired domains to 4 for ≥3 impaired domains). Correlations between mutual clinical judgment scores and between clinical judgment and GA were negligible or low., Conclusion: Correlations between clinical judgment scores and between clinical judgment and GA were poor. Most patients with multiple geriatric impairments had low 'subjective' frailty scores. Other frailty assessments, such as frailty screening tools or GA, should be considered in addition to clinical judgment when selecting older patients for potential treatment with chemotherapy., Competing Interests: Declaration of Competing Interest All authors have declared no conflicts of interest., (Copyright © 2020. Published by Elsevier Ltd.)

Introduction: Approximately 20% of older patients with breast cancer either present with metastatic disease or develop distant metastases after early breast cancer. The aims of this study were to assess the prevalence of psychosocial problems in older patients with metastatic breast cancer, and to assess longitudinal changes in functional status, psychosocial functioning, and quality of life., Methods: For this prospective cohort study, patients with metastatic breast cancer aged 70 years and older were recruited in four Dutch hospitals. A baseline geriatric assessment was performed evaluating somatic, functional and psychosocial domains. Self-administered questionnaires were performed at baseline, three and six months: the Groningen Activity Restriction Scale, Geriatric Depression Scale, Loneliness scale, Apathy scale, Distress Thermometer and EORTC-QLQ-C30. Longitudinal changes on these scales were assessed by performing crude and adjusted linear mixed models., Results: Of the 100 patients that were included and underwent a geriatric assessment, 85 patients completed the baseline self-administered questionnaires. Almost half of the patients (46%) had depressive symptoms, and up to 64% experienced distress. Apathy was present in 53%, and 36% experienced loneliness. Three- and six-month questionnaires were completed by 77 and 72 patients, respectively. Although a significant increase in loneliness between baseline and six months was seen, this size of this change was not clinically relevant. No other longitudinal changes were found., Conclusion: The prevalence of distress, depressive symptoms, apathy and loneliness in older patients with metastatic breast cancer is high. Timely detection, for which a geriatric assessment is effective, could potentially improve quality of life., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Treating elderly patients can be challenging. It is very important to carefully weigh the risks and benefits of potential treatments in individual patients. This treatment decision making can be guided by geriatric parameters. With the accumulating evidence on the added value on prediction of outcomes of (comprehensive) geriatric assessment in older patients with intensive treatment options, the question shifts from whether performing a (comprehensive) geriatric assessment is useful, to how to implement this into standard practice in a feasible and effective way. This paper discusses several issues regarding (comprehensive) geriatric assessment in elderly patients, like how to distinguish fit and frail patients and when performing a geriatric screening, geriatric assessment or a comprehensive geriatric assessment.

Cancer-related cognitive decline (CRCD) may have particularly significant consequences for older adults, impacting their functional and physical abilities, level of independence, ability to make decisions, treatment adherence, overall quality of life, and ultimately survival. In honor of Dr. Hurria's work we explore and examine multiple types of screening, assessment and non-pharmacologic treatments for CRCD. We then suggest future research and clinical practice questions to holistically appreciate the complexity of older adults with cancer's experiences and fully integrate the team-based approach to best serve this population., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Low lumbar skeletal muscle mass and density have been associated with adverse outcomes in different populations with colorectal cancer (CRC). We aimed to determine whether skeletal muscle mass, density, and physical performance are associated with postoperative complications and overall survival (OS) in older CRC patients., Methods: We analysed consecutive patients (≥70 years) undergoing elective surgery for non-metastatic CRC (stage I-III). Lumbar skeletal muscle mass and muscle density were measured using abdominal CT-images obtained prior to surgery. Low skeletal muscle mass and low muscle density were defined using commonly used thresholds and by gender-specific quartiles (Q). The preoperative use of a mobility aid served as a marker for physical performance. Cox regression proportional hazard models were used to investigate the association between the independent variables and OS., Results: 174 Patients were included (mean age 78.0), with median follow-up 2.6 years. 36 Patients (21%) used a mobility aid preoperatively. Low muscle density (Q1 vs Q4) and not muscle mass was associated with worse postoperative outcomes, including severe complications (p < 0.05). Use of a mobility aid was associated with more complications, including severe complications (39% vs 17%, p = 0.004) and OS (HR 2.65, CI 1.29-5.44, p = 0.01). However, patients with mobility aid use and low skeletal muscle mass had worse OS (HR 5.68, p = 0.003)., Conclusion: Low skeletal muscle density and not muscle mass was associated with more complications after colorectal surgery in older patients. Physical performance has the strongest association for poor surgical outcomes and should be investigated when measuring skeletal muscle mass and density., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

The number of older patients with cancer is increasing as a result of the ageing of Western societies. Immune checkpoint inhibitors have improved cancer treatment and are associated with lower rates of treatment-related toxicity compared with chemotherapy in the general population. Nonetheless, immune checkpoint inhibitors have potentially serious immune-related adverse events, which might have a greater impact on older and more vulnerable patients and potentially influence treatment efficacy and quality of life. Previous clinical trials have shown no major increase in immune-related adverse events; however, older patients are underrepresented and relatively healthy in these trials. Observational studies suggest that older and more vulnerable patients may be at a higher risk of immune-related adverse events and early treatment discontinuation. Geriatric assessment could help identify older patients who will benefit from immune checkpoint inhibitors.

Background: Older patients who are functionally compromised or frail may be at risk for loss of quality of life (QoL) after colorectal cancer (CRC) surgery. We prospectively studied health-related QoL (HRQoL) and its association with functional dependency on multiple time points before and after CRC surgery., Methods: Included were patients aged 70 years and older who underwent elective CRC surgery between 2014 and 2015 in combination with an oncogeriatric care path. HRQoL (EORTC QLQ-C30 and CR38) and activities of daily living (ADL, Barthel Index) were measured at four time-points; prior to (T0) and at 3 (T3), 6 (T6), and 12 (T12) months after surgery. Functional dependency was defined as a Barthel Index <19. Using mixed-model regression analysis associations between dependency, time and HRQoL outcomes were tested and corrected for confounders., Results: Response rate was 67% (n = 106) to two or more questionnaires; 26 (25%) patients were functionally dependent. Overall, functionally independent patients experienced a higher HRQoL than dependent patients. Compared to T0, significant and clinically relevant improvements in HRQoL after surgery were observed in functionally dependent patients: better role functioning, a higher global health, a higher summary score, less fatigue and less gastrointestinal problems (p < .05). In functional independent patients, we observed no clinically relevant change in HRQoL., Conclusion: Colorectal surgery embedded in geriatric-oncological care has a positive impact on HRQoL in older functionally dependent patients with cancer. Moderate functional dependency should not be considered a generic reason for withholding surgical treatment. Information derived from this study could be used in shared decision making., (Copyright © 2019 Elsevier Inc. All rights reserved.)

American guideline for geriatric oncology; applicable to Dutch clinical practice? The American Society of Clinical Oncology (ASCO) has recently issued a guideline for geriatric oncology that provides guidance regarding the practical assessment and management of vulnerabilities in older patients undergoing chemotherapy. The recommendations are discussed and a practical framework for implementation in Dutch oncology practice is described.

Background: Older patients are at risk for adverse outcomes after surgical treatment of cancer. Identifying patients at risk could affect treatment decisions and prevent functional decline. Screening tools are available to select patients for Geriatric Assessment. Until now their predictive value for adverse outcomes in older colorectal cancer patients has not been investigated., Objective: To study the predictive value of the Geriatric 8 (G8) and Identification of Seniors at Risk for Hospitalized Patients (ISAR-HP) screening tools for adverse outcomes after elective colorectal surgery in patients older than 70years. Primary outcomes were 30-day complication rates, secondary outcomes were the length of hospital stay and six-month mortality., Study Design and Methods: Multicentre cohort study from two hospitals in the Netherlands. Frail was defined as a G8 ≤14 and/or ISAR-HP ≥2. Odds ratio (OR) is given with 95% CI., Results: Overall, 139 patients (52%) out of 268 patients were included; 32 patients (23%) were ISAR-HP-frail, 68 (50%) were G8-frail, 20 were frail on both screening tools. Median age was 77.7years. ISAR-HP frail patients were at risk for 30-day complications OR 2.4 (CI 1.1-5.4, p=0.03), readmission OR 3.4 (1.1-11.0), cardiopulmonary complications OR 5.9 (1.6-22.6), longer hospital stay (10.3 versus 8.9day) and six-months mortality OR 4.9 (1.1-23.4). When ISAR-HP and G8 were combined OR increased for readmission, 30-day and six-months mortality. G8 alone had no predictive value., Conclusions: ISAR-HP-frail patients are at risk for adverse outcomes after colorectal surgery. ISAR-HP combined with G8 has the strongest predictive value for complications and mortality., Key Points: Patients screening frail on ISAR-HP are at increased risk for morbidity and mortality. Screening results of G8 alone was not predictive for postoperative outcomes. Predictive value increased when G8 and ISAR-HP were combined., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Although the incidences of osteoporosis and atherosclerosis increase with age, there is growing evidence that the coincidental occurrence of both diseases may be independent of age. In general, studies in men are scarce and results are inconsistent., Objective: to investigate the relationship between atherosclerosis and bone mineral density, and the influence of insulin sensitivity and low grade inflammation on this relationship in 332 men without CVD., Methods: Aortic Pulse wave velocity (PWV), augmentation index (AIX) and measurements of carotid intima media thickness (CIMT) were assessed. BMD measurements were performed with dual-X-ray absorptiometry (DEXA), subcutaneous fat by ultrasonography. Serum concentrations of lipids, hsCRP, glucose and insulin were measured. Insulin sensitivity was calculated by use of the quantitative insulin sensitivity (QUICKI). We used multivariate linear regression models to examine the association of hsCRP, insulin sensitivity, PWV, Aix, CIMT with BMD., Results: A higher CIMT was significantly associated with higher BMD after multivariate adjustment (ß 99.7; p=0.02). Further adjustment for weight attenuated the estimates towards non-significant. No association was found between PWV or AIX and BMD. Lower insulin sensitivity was associated with higher BMD (ß -645.1; p<0.01). After adjustment for weight this association was no longer significant. A similar effect was seen for the association between hsCRP and BMD., Conclusion: In this population of healthy, non-obese, men without a history of cardiovascular disease the positively association between cardiovascular parameters and BMD was mainly explained by weight, suggesting that in this population weight plays a protective role in the development of osteoporosis., Competing Interests: Frederiek van den Bos – Reports no disclosures; Marielle Emmelot-Vonk – Reports no disclosures; Harald Verhaar – Reports no disclosure; Yvonne van der Schouw – Reports no disclosures

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.

Background: Because of the time-consuming aspect of geriatric assessments, cancer specialists are seeking shorter screening tools to distinguish fit and frail patients. We analyzed the predictive value of the Geriatric 8 (G8) and Identification of Seniors at Risk for Hospitalized Patients (ISAR-HP) in elderly patients with lung cancer., Patients and Methods: From January 2014 to April 2016, the data from patients with lung cancer aged > 70 years at 2 teaching hospitals in the Netherlands were included in a database. The patients were classified as potentially frail if they had a G8 of ≤ 14 or ISAR-HP of ≥ 2., Results: Of the 142 included patients (median age, 77 years; interquartile range, 73-82 years), 108 (76%) were potentially frail. After correction for possible confounders, the potentially frail patients had a significantly greater risk of 1-year mortality (hazard ratio [HR], 4.08; 95% confidence interval [CI] 1.67-9.99; P = .02). Higher disease stage (HR, 1.72; 95% CI, 1.40-2.12; P < .001) was also a significant predictor of mortality; however, initial treatment (standard or otherwise) and age were not. When using both screening instruments separately, an impaired score on the G8 and higher disease stage were the variables remaining in the regression analyses (HR for impaired G8, 3.01; 95% CI, 1.35-6.72; P < .001). Patients with impaired scores on the ISAR-HP and G8 had more geriatric impairments than did patients with only an impaired G8 score., Conclusion: G8 screening is useful for the prognostication of elderly patients with lung cancer and could be used in combination with ISAR-HP to increase specificity at the cost of sensitivity. Using the ISAR-HP as the only screening tool would be insufficient., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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.

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.

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.

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.

Clostridium botulinum is a highly dangerous pathogen that forms very resistant endospores that are ubiquitous in the environment, and which, under favorable conditions germinate to produce vegetative cells that multiply and form the exceptionally potent botulinum neurotoxin. To improve the control of botulinum neurotoxin-forming clostridia, it is important to understand the mechanisms involved in spore germination. Here we present models for spore germination in C. botulinum based on comparative genomics analyses, with C. botulinum Groups I and III sharing similar pathways, which differ from those proposed for C. botulinum Groups II and IV. All spores germinate in response to amino acids interacting with a germinant receptor, with four types of germinant receptor identified [encoded by various combinations of gerA, gerB , and gerC genes ( gerX )]. There are three gene clusters with an ABC-like configuration; ABC [ gerX1 ], ABABCB [ gerX2 ] and ACxBBB [ gerX4 ], and a single CA-B [ gerX3 ] gene cluster. Subtypes have been identified for most germinant receptor types, and the individual GerX subunits of each cluster show similar grouping in phylogenetic trees. C. botulinum Group I contained the largest variety of gerX subtypes, with three gerX1 , three gerX2 , and one gerX3 subtypes, while C. botulinum Group III contained two gerX1 types and one gerX4 . C. botulinum Groups II and IV contained a single germinant receptor, gerX3 and gerX1 , respectively. It is likely that all four C. botulinum Groups include a SpoVA channel involved in dipicolinic acid release. The cortex-lytic enzymes present in C. botulinum Groups I and III appear to be CwlJ and SleB, while in C. botulinum Groups II and IV, SleC appears to be important.

Lung cancer is predominantly a disease of the elderly: one half of all newly diagnosed patients will be > 70 years old. In the Netherlands, > 12,000 new cases are diagnosed annually. We sought to assemble all available evidence on the relevance of a geriatric assessment for lung cancer patients. A systematic Medline and Embase search was performed for studies in which a geriatric assessment was used to detect health issues or that had addressed the association between a baseline geriatric assessment (composed of ≥ 2 of the following domains: cognitive function, mood/depression, nutritional status, activities of daily living, instrumental activities of daily living, polypharmacy, objectively measured physical capacity, social support and frailty) and outcome. A total of 23 publications from 18 studies were included. The median age of patients was 76 years (range, 73-81 years). Despite generally good Eastern Cooperative Oncology Group performance status, the prevalence of geriatric impairments was high, with the median ranging from 29% for cognitive impairment to 70% for instrumental activities of daily living impairment. Objective physical capacity and nutritional status, as items of the geriatric assessment, had a consistent association with mortality. The information revealed by a geriatric assessment led to changes in oncologic treatment and nononcologic interventions. The present review has demonstrated that a geriatric assessment can detect multiple health issues not reflected in the Eastern Cooperative Oncology Group performance status. Impairments in geriatric domains have predictive value for mortality and appear to be associated with treatment completion. It would be useful to develop and validate an individualized treatment algorithm that includes these geriatric domains., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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.

Objective: Adequate decision-making concerning elderly patients with colorectal cancer requires accurate information regarding the risks of treatment. We analysed the post-operative outcomes and survival following colorectal resections in the oldest old patients (≥ 85 years old)., Design: Retrospective study., Method: We analysed the data from 2011 and 2012 of all patients with colorectal carcinoma, stage I-III, from two national databases, namely the Dutch Surgical Colorectal Audit registry (DSCA) and the Netherlands Cancer Registry (NKR)., Results: The study included over 1200 elderly patients. The postoperative complication rate was 41%. The frequency of cardiopulmonary complications rose rapidly with age, from 11% in those < 70 years to 38% in those aged > 85 years. The postoperative 30-day mortality rate was 10% for the oldest old patients, whereas it was 14% after three months, 24% after one year and 36% after two years. After correction for expected mortality in the general population, excess mortality for the oldest old was 12% in the first year and 3% in the second year., Conclusion: For patients aged ≥ 85 years who undergo surgical resection for colorectal carcinoma, high rates of cardiopulmonary complications and excess mortality in the first year after surgery are observed. We propose that these data could be analysed together with information regarding individual patients' health status, to enable optimisation of future decision-making regarding potential surgical intervention in elderly patients.

Older patients with colorectal cancer are faced with the dilemma of choosing between the short-term risks of treatment and the long-term risks of insufficiently treated disease. In addition to treatment-related morbidity and mortality, patients may suffer from loss of physical capacity. The purpose of this review was to gather all available evidence regarding long-term changes in physical functioning and role functioning after colorectal cancer treatment, by performing a systematic Medline and Embase search. This search yielded 27 publications from 23 studies. In 16 studies addressing physical functioning after rectal cancer treatment, a median drop of 10% (range -26% to -5%) in the mean score for this item at three months. At six months, mean score was still 7% lower than baseline (range -18% to 0%) and at twelve months 5% lower (range -13% to +5%). For role functioning (i.e. ability to perform daily activities) after rectal cancer treatment, scores were -18% (range -39% to -2%), -8% (range -23% to +6%) and -5% (range -17% to +10%) respectively. Elderly patients experience the greatest and most persistent decline in self-care capacity (up to 61% at one year). This systematic review demonstrates that both physical functioning and role functioning are significantly affected by colorectal cancer surgery. Although initial losses are recovered partially during follow-up, there is a permanent loss in both aspects of physical capacity, in patients of all ages but especially in the elderly. This aspect should be included in patient counselling regarding surgery., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: patients with Parkinson's disease (PD) have a high risk of sustaining osteoporotic fractures as a result of falls and reduced bone mass., Objective: to summarise the underlying pathophysiological mechanisms of bone loss in PD by reviewing the available literature., Methods: a Medline search was performed for articles published between January 1975 and January 2011, using the keywords 'bone mineral density', 'bone loss', 'bone metabolism', 'osteoporosis', 'osteopenia', 'Parkinson's disease' and 'Parkinsonism'., Results: PD patients have a lower bone mineral density (BMD) than age-matched controls. Bone loss in PD is multifactorial, resulting from immobility, decreased muscle strength, and low body weight. Vitamin D deficiency is also important, not only because it reduces BMD, but also because cell function in the substantia nigra depends on vitamin D. Lastly, hyperhomocysteinaemia, an independent risk factor for osteoporosis, is common in PD, due to levodopa use, as well as vitamin B12 and folic acid deficiency. A few studies have demonstrated that treatment with bisphosphonates, vitamin D and calcium can increase BMD and reduce fractures in PD patients., Conclusion: bone loss in PD is multifactorial. It is clinically important because of the concomitant risk of fractures. Screening for osteoporosis should be considered more often, and therapeutic interventions should be initiated.

Background: Charles Bonnet syndrome is characterised by complex visual hallucinations in patients who have visual disturbances but no cognitive disorders. The diagnosis is often missed., Case Description: An 88-year-old vital woman was referred to the emergency department due to anxiety and restlessness. Her symptoms began after she had started using antipsychotic drugs for visual hallucinations. The patient's visual acuity appeared to be markedly reduced. The antipsychotics were discontinued and the reason behind the patient's symptoms was explained to her: Charles Bonnet syndrome. The anxiety and restlessness disappeared and the frequency of the hallucinations declined., Conclusion: This patient had Charles Bonnet syndrome. If visual hallucinations occur for the first time after the 40th year of life, a somatic cause should first be ruled-out. Refraining from treating Charles Bonnet syndrome with pharmacological agents is advised in light of their many side effects and little evidence of being beneficial for this condition.