A comparison of treatment allocation and survival between younger and older patients with HER2-overexpressing de novo metastatic breast cancer.

INTRODUCTION: There have been several developments in the treatment of HER2-overexpressing metastatic breast cancer. However, pivotal trials mainly included younger and healthier patients, resulting in a lack of information about the benefits and harms of treatment for most older patients. The aim of this study was to provide an overview of the differences in treatment allocation and survival outcomes over time between younger and older patients with HER2-overexpressing metastatic breast cancer. MATERIALS AND METHODS: All patients from the Netherlands Cancer Registry with de novo metastatic breast cancer between 2005 and 2021 were included. Patients were divided into three age groups: <65, 65-74, and ≥ 75 years. Changes in treatment allocation were graphically depicted over time. Cox proportional hazard models were used to calculate overall survival and Poisson models for relative survival. RESULTS: Overall, 2,722 patients were included. Between 2005 and 2021, the use of targeted therapy as first-line treatment increased for all age groups (<65 years from 33.8% to 90.6%, p < 0.001; 65-74 years from 29.2% to 86.5%, p = 0.001; ≥75 years from 4.3% to 55.8%, p < 0.001). Use of chemotherapy as first-line treatment also increased for all age groups (<65 years from 73.5% to 89.8%, p < 0.001; 65-74 years from 50.0% to 78.4%, p = 0.01; ≥75 years from 8.7% to 37.2%, p = 0.04). Although not statistically significant, the use of endocrine therapy, both as monotherapy and in combination with targeted therapy in the first line, decreased (<65 years 19.1% to 5.5%, p < 0.001; 65-74 years 25.0% to 13.5%, p = 0.03; ≥75 years 65.2% to 37.2%, p = 0.16). Changes in relative and overall survival were similar and improved in all age groups, but most in the youngest age group (relative excess risk [RER] 0.93, 95% confidence interval [CI] 0.91-0.94 per year, p < 0.001), and least in patients ≥75 (RER 0.96, 95% CI 0.93-0.98 per year, p = 0.001). DISCUSSION: The use of first-line chemotherapy and targeted therapy increased in all age groups, while the use of endocrine therapy decreased over time. Nevertheless, the uptake of chemotherapy and targeted therapies was substantially slower in the oldest age group. Overall survival and relative survival improved for all age groups, but these improvements were smaller in the older age groups.

Preparing for future pandemics: frailty associates with mortality in hospitalised older people during the entire COVID-19 pandemic, a Dutch multicentre cohort study.

PURPOSE: Viral mutations and improved prevention or treatment options may have changed the association of frailty with mortality throughout the COVID-19 pandemic. We investigated how associations of frailty with in-hospital mortality changed throughout the pandemic in older people hospitalised for COVID-19. METHODS: The COVID-OLD study included COVID-19 patients aged ≥ 70 years hospitalised during the first (early 2020), second (late 2020), third (late 2021) or fourth wave (early 2022). Based on the clinical frailty scale, patients were categorised as fit (1-3), pre-frail (4-5) or frail (6-9). Associations of frailty with in-hospital mortality were assessed with pairwise comparisons with fit as reference category and modelled using binary logistic regression adjusted for age and sex. RESULTS: This study included 2362 patients (mean age 79.7 years, 60% men). In the first wave, in-hospital mortality was 46% in patients with frailty and 27% in fit patients. In-hospital mortality decreased in each subsequent wave to 25% in patients with frailty and 11% in fit patients in the fourth wave. After adjustments, an overall higher risk of in-hospital mortality was found in frail (OR 2.26, 95% CI: 1.66-3.07) and pre-frail (OR 1.73, 95% CI: 1.27-2.35) patients compared to fit patients, which did not change over time (p for interaction = 0.74). CONCLUSIONS: Frailty remained associated with a higher risk of in-hospital mortality throughout the entire COVID-19 pandemic, although overall in-hospital mortality rates decreased. Frailty therefore remains a relevant risk factor in all stages of a pandemic and is important to consider in prevention and treatment guidelines for future pandemics.

Toxicity in Older Patients with Cancer Receiving Immunotherapy: An Observational Study.

BACKGROUND: Checkpoint inhibition has emerged as an effective treatment strategy for a variety of cancers, including in older adults. However, older patients with cancer represent a heterogenous group as they can vary widely in frailty, cognition, and physical status. OBJECTIVE: This study aims to investigate the association between clinical frailty and immune-related treatment toxicity, hospitalization, and treatment discontinuation due to immune-related treatment toxicity in older patients treated with checkpoint inhibitors. METHODS: Patients aged 70 years and older treated with checkpoint inhibitors were selected from the TENT study, IMAGINE study, and "Tolerability and safety of immunotherapy study". Clinical frailty was assessed by the Geriatric-8 test score and World Health Organization (WHO) status. Outcomes were grades 3-5 toxicity, hospitalization, and treatment discontinuation due to toxicity during treatment. RESULTS: Of 99 patients included, 22% had comorbidities. While 33% of the patients were considered frail based on an abnormal Geriatric-8 test score of < 15, physical impairments were considered absent in 51% (WHO score of 0) and mild in 40% (WHO score of 1). Despite the limited sample size of the cohort, consistent trends were observed with patients with an abnormal Geriatric-8 test score of < 15 or a higher WHO score of 1 for having higher odds of toxicity [odds ratio (OR) 2.32 (95% CI 0.41-13.02); OR 1.33 (95% CI 0.45-4.17)], treatment discontinuation due to immune-related treatment toxicity [OR 2.25 (95% CI 0.61-8.31); OR 2.18 (95% CI 0.7-6.73)], and hospitalization due to immune-related treatment toxicity [OR 3.72 (95% CI 0.39-35.4); OR 1.31 (95% CI 0.35-4.9)]. Moreover, in a sub-analysis, we observed that the treatment discontinuation due to immune-related treatment toxicity occurred often in patients with grade 1-2 toxicity as well. CONCLUSIONS: Although not statistically significant, in older patients treated with immunotherapy in a real-life population with cancer, we observed consistent trends towards increased toxicity, hospitalization, and treatment discontinuation with increasing frailty. Larger studies are needed to confirm these exploratory results. Moreover, older patients with a lower toxicity grade 1-2 experienced early treatment discontinuation frequently, suggesting a lower tolerance of toxicity.

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.

A Grounded Theory of Interdisciplinary Communication and Collaboration in the Outpatient Setting of the Hospital for Patients with Multiple Long-Term Conditions.

Interdisciplinary communication and collaboration are crucial in the care of people with multiple long-term conditions (MLTCs) yet are often experienced as insufficient. Through the lens of complexity science, this study aims to explain how healthcare professionals (HCPs) adapt to emerging situations in the care of patients with MLTC by examining interdisciplinary communication and collaboration in the outpatient hospital setting. We used the constant comparative method to analyze transcribed data from seven focus groups with twenty-one HCPs to generate a constructivist grounded theory of 'interdisciplinary communication and collaboration in the outpatient setting of the hospital for patients with multiple long-term conditions'. Our theory elucidates the various pathways of communication and collaboration. Why, when, and how team members choose to collaborate influences if and to what degree tailored care is achieved. There is great variability and unpredictability to this process due to internalized rules, such as beliefs on the appropriateness to deviate from guidelines, and the presence of an interprofessional identity. We identified organizational structures that influence the dynamics of the care team such as the availability of time and financial compensation for collaboration. As we strive for tailored care for patients with MLTC, our theory provides promising avenues for future endeavors.

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.

Older patients' experiences with and attitudes towards an oncogeriatric pathway: A qualitative study.

INTRODUCTION: To tailor treatment for older patients with cancer, an oncogeriatric care pathway has been developed in the Leiden University Medical Center. In this care pathway a geriatric assessment is performed and preferences concerning cancer treatment options are discussed. This study aimed to explore patient experiences with and attitudes towards this pathway. MATERIALS AND METHODS: A qualitative study was performed using an exploratory descriptive approach. Individual face-to-face semi-structured interviews were conducted with older patients (≥70 years) who had followed the oncogeriatric care pathway in the six months prior to the interview. The interviews were audio-recorded and transcribed verbatim. The transcripts were analyzed inductively using thematic analysis. RESULTS: After interviews with 14 patients with a median age of 80 years, three main themes were identified. (1) Patients' positive experiences with the oncogeriatric pathway: Patients appreciated the attitudes of the healthcare professionals and felt heard and understood. (2) Unmet information needs about the oncogeriatric care pathway: Patients experienced a lack of information about the aim and process. (3) Incomplete information for decision-making: Most patients were satisfied with decision-making process. However, treatment decisions had often been made before oncogeriatric consultation. No explicit naming and explaining of different available treatment options had been provided, nor had risk of physical or cognitive decline during and after treatment been addressed. DISCUSSION: Older patients had predominately positive attitudes towards the oncogeriatric care pathway. Most patients were satisfied with the treatment decision. Providing information on the aim and process of the care pathway, available treatment options, and treatment-related risks of cognitive and physical decline may further improve the oncogeriatric care pathway and the decision-making process.

The prognostic value of a geriatric risk score for older patients undergoing emergency surgery of colorectal cancer: A retrospective cohort study.

INTRODUCTION: Emergency surgery of colorectal cancer is associated with high mortality rates in older patients. We investigated whether information on four geriatric domains has prognostic value for 30-day mortality and postoperative morbidity including severe complications. MATERIALS AND METHODS: All consecutive patients aged 70 years or older who underwent emergency colorectal cancer surgery in six Dutch hospitals (2014-2017) were studied. Presence of geriatric risk factors was scored prior to surgery as either 0 (risk absent) or 1 (risk present) in each of four geriatric domains and summed up to calculate a sumscore with a value between 0 and 4. In addition, we separately investigated the use of a mobility aid. Primary outcome was 30-day mortality. Secondary outcomes were any postoperative complications and severe complications. Multivariable logistic regression model was used to evaluate the sumscore and outcomes. RESULTS: Two hundred seven patients were included. Median age was 79.4 years. One hundred seventy-five patients (76%) presented with obstruction, 22 (11%) with a perforation, and 17 (8%) with severe anemia. Mortality rates were 2.9%, 13.6%, and 29.6% for patients with a sumscore of 0, 1-2, and 3-4 respectively, with odds ratio (OR) 4.8 [95% confidence interval (CI) 1.03-22.95] and OR 10.6 [95% CI 1.99-56.34] for a sumscore of 1-2 and 3-4 respectively. Use of a mobility aid was associated with increased mortality OR 8.0 [95% CI 2.74-23.43] and severe complications OR 2.31 [95% CI 1.17-4.55]. DISCUSSION: This geriatric sumscore and the use of a mobility aid have strong association with 30-day mortality after emergency surgery of colorectal cancer. This could provide better insight into surgical risk and help select high-risk patients for alternative strategies.

Geriatric predictors of response and adverse events in older patients with cancer treated with immune checkpoint inhibitors: A systematic review.

BACKGROUND: Immunotherapy with checkpoint inhibitors (ICI) has improved cancer treatment in recent years. Older and frail patients are frequently treated with ICIs, but since they have been underrepresented in previous clinical trials, the real impact of ICI in this patient group is not well defined. The aim of this systematic review was to evaluate the evidence for associations between geriatric impairments and treatment outcomes in older patients with advanced and metastatic cancer treated with ICIs. METHODS: A systematic search was conducted in PubMed, Cochrane Library, Embase, and Web of Science for relevant articles published before June 2022. Studies investigating the association between impairments in at least two geriatric domains and treatment outcome were considered eligible. Data extraction and risk of bias assessment using the QUIPS tool was performed independently by two investigators. RESULTS: A total of nine studies were included. Median sample size of the studies was 92 patients (interquartile range (IQR) 47-113), with a median of 26 frail patients (IQR 21-35). Five studies investigated disease-related and survival outcomes, and two of them found a statistically significant association between geriatric impairments and either survival or disease progression. Eight studies investigated toxicity outcomes, and two of them showed a statistically significant association between geriatric impairments and immune-related adverse events (irAEs). Few studies suggested a relation between geriatric impairments and worse clinical outcomes. CONCLUSIONS: Only a few studies have investigated the association between geriatric impairments and treatment outcomes and these studies were small. Older patients with geriatric impairments seem to be more likely to experience irAEs, but larger studies that include frail patients and use geriatric screening tools are required to confirm this association. These studies will be essential to improve the development of specific strategies to deal with frail patients.

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.

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.

Chemotherapy-Related Toxic Effects and Quality of Life and Physical Functioning in Older Patients.

Importance: Although older patients are at increased risk of developing grade 3 or higher chemotherapy-related toxic effects, no studies, to our knowledge, have focused on the association between toxic effects and quality of life (QOL) and physical functioning. Objective: To investigate the association between grade 3 or higher chemotherapy-related toxic effects and QOL and physical functioning over time in older patients. Design, Setting, and Participants: In this prospective, multicenter cohort study, patients aged 70 years or older who were scheduled to receive chemotherapy with curative or palliative intent and a geriatric assessment were included. Patients were treated with chemotherapy between December 2015 and December 2021. Quality of life and physical functioning were analyzed at baseline and after 6 months and 12 months. Exposures: Common Terminology Criteria for Adverse Events grade 3 or higher chemotherapy-related toxic effects. Main Outcomes and Measures: The main outcome was a composite end point, defined as a decline in QOL and/or physical functioning or mortality at 6 months and 12 months after chemotherapy initiation. Associations between toxic effects and the composite end point were analyzed with multivariable logistic regression models. Results: Of the 276 patients, the median age was 74 years (IQR, 72-77 years), 177 (64%) were male, 196 (71%) received chemotherapy with curative intent, and 157 (57%) had gastrointestinal cancers. Among the total patients, 145 (53%) had deficits in 2 or more of the 4 domains of the geriatric assessment and were classified as frail. Grade 3 or higher toxic effects were observed in 94 patients (65%) with frailty and 66 (50%) of those without frailty (P = .01). Decline in QOL and/or physical functioning or death was observed in 76% of patients with frailty and in 64% to 68% of those without frailty. Among patients with frailty, grade 3 or higher toxic effects were associated with the composite end point at 6 months (odds ratio [OR], 2.62; 95% CI, 1.14-6.05) but not at 12 months (OR, 1.09; 95% CI, 0.45-2.64) and were associated with mortality at 12 months (OR, 3.54; 95% CI, 1.50-8.33). Toxic effects were not associated with the composite end point in patients without frailty (6 months: OR, 0.76; 95% CI, 0.36-1.64; 12 months: OR, 1.06; 95% CI, 0.46-2.43). Conclusions and Relevance: In this prospective cohort study of 276 patients aged 70 or older who were treated with chemotherapy, patients with frailty had more grade 3 or higher toxic effects than those without frailty, and the occurrence of toxic effects was associated with a decline in QOL and/or physical functioning or mortality after 1 year. Toxic effects were not associated with poor outcomes in patients without frailty. Pretreatment frailty screening and individualized treatment adaptions could prevent a treatment-related decline of remaining health.

Supporting older patients in making healthcare decisions: The effectiveness of decision aids; A systematic review and meta-analysis.

OBJECTIVE: To systematically review randomized controlled trials and clinical controlled trials evaluating the effectiveness of Decision Aids (DAs) compared to usual care or alternative interventions for older patients facing treatment, screening, or care decisions. METHODS: A systematic search of several databases was conducted. Eligible studies included patients ≥ 65 years or reported a mean of ≥ 70 years. Primary outcomes were attributes of the choice made and decision making process, user experience and ways in which DAs were tailored to older patients. Meta-analysis was conducted, if possible, or outcomes were synthesized descriptively. RESULTS: Overall, 15 studies were included. Using DAs were effective in increasing knowledge (SMD 0.90; 95% CI [0.48, 1.32]), decreasing decisional conflict (SMD -0.15; 95% CI [-0.29, -0.01]), improving patient-provider communication (RR 1.67; 95% CI [1.21, 2.29]), and preparing patients to make an individualized decision (MD 35.7%; 95% CI [26.8, 44.6]). Nine studies provided details on how the DA was tailored to older patients. CONCLUSION: This review shows a number of favourable results for the effectiveness of DAs in decision making with older patients. PRACTICE IMPLICATIONS: Current DAs can be used to support shared decision making with older patients when faced with treatment, screening or care decisions.

Evaluation of an integrated care pathway for out-of-hospital treatment of older adults with an acute moderate-to-severe lower respiratory tract infection or pneumonia: protocol of a mixed methods study.

INTRODUCTION: Older adults with an acute moderate-to-severe lower respiratory tract infection (LRTI) or pneumonia are generally treated in hospitals causing risk of iatrogenic harm such as functional decline and delirium. These hospitalisations are often a consequence of poor collaboration between regional care partners, the lack of (acute) diagnostic and treatment possibilities in primary care, and the presence of financial barriers. We will evaluate the implementation of an integrated regional care pathway ('The Hague RTI Care Bridge') developed with the aim to treat and coordinate care for these patients outside the hospital. METHODS AND ANALYSIS: This is a prospective mixed methods study. Participants will be older adults (age≥65 years) with an acute moderate-to-severe LRTI or pneumonia treated outside the hospital (care pathway group) versus those treated in the hospital (control group). In addition, patients, their informal caregivers and treating physicians will be asked about their experiences with the care pathway. The primary outcome of this study will be the feasibility of the care pathway, which is defined as the percentage of patients treated outside the hospital, according to the care pathway, whom fully complete their treatment without the need for hospitalisation within 30 days of follow-up. Secondary outcomes include the safety of the care pathway (30-day mortality and occurrence of complications (readmissions, delirium, falls) within 30 days); the satisfaction, usability and acceptance of the care pathway; the total number of days of bedridden status or hospitalisation; sleep quantity and quality; functional outcomes and quality of life. ETHICS AND DISSEMINATION: The Medical Research Ethics Committee Leiden The Hague Delft (reference number N22.078) has confirmed that the Medical Research Involving Human Subjects Act does not apply to this study. The results will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN68786381.

Medication optimization in older adults with advanced cancer and a limited life expectancy: A prospective observational study.

INTRODUCTION: Polypharmacy is common in older adults with cancer and is associated with drug related problems (DRPs) and potentially inappropriate medication (PIM). We introduced a medication optimization care pathway for older adults with advanced cancer and a limited life expectancy and studied the prevalence of DRPs and PIMs as well as the adherence to medication-related recommendations and the patient satisfaction. MATERIALS AND METHODS: A medication review was performed in patients aged ≥65 years with polypharmacy and a life expectancy of <24 months. Recommendations on adjustments of medication were discussed in a multidisciplinary team including a pharmacist, an oncologist, and a geriatrician. Implementation of the recommendations was left to the discretion of the oncologist. Four weeks after the implementation, the patient filled a questionnaire to assess satisfaction. RESULTS: One hundred twenty patients were included. The mean age was 75 years and 39% were female. A mean of 12 medications was used. The median number of DRP was 6.0 per patient and median number of PIMs was 3.0 per patient. Overtreatment accounted for 26% of DRP and the most frequently involved drug classes were antihypertensive medication (22%), non-opioid analgesics (22%), and antilipemics (12%). The multidisciplinary team accepted 78% of the recommendations of the pharmacist and the oncologist implemented 54% of the recommendations. Overall, patients were satisfied or very satisfied with the intervention. DISCUSSION: DRPs and PIMs are highly prevalent in this population and can be reduced by a multidisciplinary medication optimization intervention. Patients appreciate the medication optimization intervention and are satisfied with the intervention.

The association of blood biomarkers with treatment response and adverse health outcomes in older patients with solid tumors: A systematic review.

INTRODUCTION: Blood biomarkers are potentially useful prognostic markers and may support treatment decisions, but it is unknown if and which biomarkers are most useful in older patients with solid tumors. The aim of this systematic review was to evaluate the evidence on the association of blood biomarkers with treatment response and adverse health outcomes in older patients with solid tumors. MATERIALS AND METHODS: A literature search was conducted in five databases in December 2022 to identify studies on blood biomarkers measured before treatment initiation, not tumor specific, and outcomes in patients with solid tumors aged ≥60 years. Studies on any type or line of oncologic treatment could be included. Titles and abstracts were screened by three authors. Data extraction and quality assessment, using the Quality in Prognosis Studies (QUIPS) checklist, were performed by two authors. RESULTS: Sixty-three studies were included, with a median sample size of 138 patients (Interquartile range [IQR] 99-244) aged 76 years (IQR 72-78). Most studies were retrospective cohort studies (63%). The risk of bias was moderate in 52% and high in 43%. Less than one-third reported geriatric parameters. Eighty-six percent examined mortality outcomes, 37% therapeutic response, and 37% adverse events. In total, 77 unique markers were studied in patients with a large variety of tumor types and treatment modalities. Neutrophil-to-lymphocyte ratio (20 studies), albumin (19), C-reactive protein (16), hemoglobin (14) and (modified) Glasgow Prognostic Score ((m)GPS) (12) were studied most often. The vast majority showed no significant association of these biomarkers with outcomes, except for associations between low albumin and adverse events and high (m)GPS with mortality. DISCUSSION: Most studies did not find a significant association between blood biomarkers and clinical outcomes. The interpretation of current evidence on prognostic blood biomarkers is hampered by small sample sizes and inconsistent results across heterogeneous studies. The choice for blood biomarkers in the majority of included studies seemed driven by availability in clinical practice in retrospective cohort studies. Ageing biomarkers are rarely studied in older patients with solid tumors. Further research is needed in larger and more homogenous cohorts that combine clinical parameters and biomarkers before these can be used in clinical practice.

Mental health outcomes in older breast cancer survivors: Five-year follow-up from the CLIMB study.

BACKGROUND: There is a lack of information on mental health outcomes for the increasing older population. Therefore, the aim of the current study is to assess depressive symptoms, loneliness, and apathy in older patients with breast cancer within the first 5 years after diagnosis. METHODS: Women aged ≥70 years with early-stage breast cancer were included. Multivariate linear mixed models were used to assess longitudinal changes in symptoms of depression (according to the 15-item Geriatric Depression Scale), loneliness (according to the De Jong Gierveld Loneliness Scale) and apathy (according to the Starkstein Apathy Scale) over time at 3, 9, 15, 27 and 60 months follow-up. RESULTS: In total, 299 patients were included (mean [standard deviation (SD)] age: 75.8 [5.2] years). At 3 months follow-up, shortly after the acute treatment, 10% of patients had significant depressive symptoms, while loneliness and apathy were present in 31% and 41% of all patients, respectively. Depression, loneliness and apathy scores showed no clinically relevant changes over time in the whole cohort. Patients who received adjuvant systemic therapies (i.e. endocrine therapy and/or chemotherapy and/or targeted therapy (trastuzumab)) had similar mental health outcomes as those who did not. However, frail patients had more symptoms (p < 0.001) and were more prone to develop depressive symptoms over time than non-frail patients (p = 0.002). DISCUSSION: Depression, loneliness and apathy were frequently observed in older women with breast cancer and did not change over time. Patients who received adjuvant systemic therapies had similar mental health outcomes as those who did not. However, frail patients were at higher risk to experience these symptoms.

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.