Allocation and value of curative oncological treatment in frail and fit older patients with esophageal cancer: An observational cohort study.

INTRODUCTION: The Value-Based Health Care (VBHC) model of care provides insights into patient characteristics, outcomes, and costs of care delivery that help clinicians counsel patients. This study compares the allocation and value of curative oncological treatment in frail and fit older patients with esophageal cancer in a dedicated VBHC pathway. MATERIALS AND METHODS: Data was collected from patients with primary esophageal cancer without distant metastases, aged 70 years or older, and treated at a Dutch tertiary care hospital between 2015 and 2019. Geriatric assessment (GA) was performed. Outcomes included treatment discontinuation, mortality, quality of life (QoL), and physical functioning over a one-year period. Direct hospital costs were estimated using activity-based costing. RESULTS: In this study, 89 patients were included with mean age 75 years. Of 56 patients completing GA, 19 were classified as frail and 37 as fit. For frail patients, the treatment plan was chemoradiotherapy and surgery (CRT&S) in 68% (13/19) and definitive chemoradiotherapy (dCRT) in 32% (6/19); for fit patients, CRT&S in 84% (31/37) and dCRT in 16% (6/37). Frail patients discontinued chemotherapy more often than fit patients (26% (5/19) vs 11% (4/37), p = 0.03) and reported lower QoL after six months (mean 0.58 [standard deviation (SD) 0.35] vs 0.88 [0.25], p < 0.05). After one year, 11% of frail and 30% of fit patients reported no decline in physical functioning and QoL and survived. Frail and fit patients had comparable mean direct hospital costs (€24 K [SD €13 K] vs €23 K [SD €8 K], p = 0.82). DISCUSSION: The value of curative oncological treatment was lower for frail than for fit patients because of slightly worse outcomes and comparable costs. The utility of the VBHC model of care depends on the availability of sufficient data. Real-world evidence in VBHC can be used to inform treatment decisions and optimization in future patients by sharing results and monitoring performance over time. TRIAL REGISTRATION: The study was retrospectively registered at the Netherlands Trial Register (NTR), trial number NL8107 (date of registration: 22-10-2019).

DOSAGE study: protocol for a phase III non-inferiority randomised trial investigating dose-reduced chemotherapy for advanced colorectal cancer in older patients.

INTRODUCTION: Treating older adults with chemotherapy remains a challenge, given their under-representation in clinical trials and the lack of robust treatment guidelines for this population. Moreover, older patients, especially those with frailty, have an increased risk of developing chemotherapy-related toxicity, resulting in a decreased quality of life (QoL), increased hospitalisations and high healthcare costs. Phase II trials have suggested that upfront dose reduction of chemotherapy can reduce toxicity rates while maintaining efficacy, leading to fewer treatment discontinuations and an improved QoL. The DOSAGE aims to show that upfront dose-reduced chemotherapy in older patients with metastatic colorectal cancer is non-inferior to full-dose treatment in terms of progression-free survival (PFS), with adaption of the treatment plan (monotherapy or doublet chemotherapy) based on expected risk of treatment toxicity. METHODS AND ANALYSIS: The DOSAGE study is an investigator-initiated phase III, open-label, non-inferiority, randomised controlled trial in patients aged≥70 years with metastatic colorectal cancer eligible for palliative chemotherapy. Based on toxicity risk, assessed using the Geriatric 8 (G8) tool, patients will be stratified to either doublet chemotherapy (fluoropyrimidine with oxaliplatin) or fluoropyrimidine monotherapy. Patients classified as low risk will be randomised between a fluoropyrimidine plus oxaliplatin in either full-dose or with an upfront dose reduction of 25%. Patients classified as high risk will be randomised between fluoropyrimidine monotherapy in either full-dose or with an upfront dose reduction. In the dose-reduced arm, dose escalation after two cycles is allowed. The primary outcome is PFS. Secondary endpoints include grade≥3 toxicity, QoL, physical functioning, number of treatment cycles, dose reductions, hospital admissions, overall survival, cumulative received dosage and cost-effectiveness. Considering a median PFS of 8 months and non-inferiority margin of 8 weeks, we shall include 587 patients. The study will be enrolled in 36 Dutch Hospitals, with enrolment scheduled to start in July 2024. This study will provide new evidence regarding the effect of dose-reduced chemotherapy on survival and treatment outcomes, as well as the use of the G8 to choose between doublet chemotherapy or monotherapy. Results will contribute to a more individualised approach in older patients with metastatic colorectal cancer, potentially leading to improved QoL while maintaining survival benefits. ETHICS AND DISSEMINATION: This trial has received ethical approval by the ethical committee Leiden Den Haag Delft (P24.018) and will be approved by the Institutional Ethical Committee of the participating institutions. The results will be disseminated in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT06275958.

The performance of metabolomics-based prediction scores for mortality in older patients with solid tumors.

Prognostic information is needed to balance benefits and risks of cancer treatment in older patients. Metabolomics-based scores were previously developed to predict 5- and 10-year mortality (MetaboHealth) and biological age (MetaboAge). This study aims to investigate the association of MetaboHealth and MetaboAge with 1-year mortality in older patients with solid tumors, and to study their predictive value for mortality in addition to established clinical predictors. This prospective cohort study included patients aged ≥ 70 years with a solid malignant tumor, who underwent blood sampling and a geriatric assessment before treatment initiation. The outcome was all-cause 1-year mortality. Of the 192 patients, the median age was 77 years. With each SD increase of MetaboHealth, patients had a 2.32 times increased risk of mortality (HR 2.32, 95% CI 1.59-3.39). With each year increase in MetaboAge, there was a 4% increased risk of mortality (HR 1.04, 1.01-1.07). MetaboHealth and MetaboAge showed an AUC of 0.66 (0.56-0.75) and 0.60 (0.51-0.68) for mortality prediction accuracy, respectively. The AUC of a predictive model containing age, primary tumor site, distant metastasis, comorbidity, and malnutrition was 0.76 (0.68-0.83). Addition of MetaboHealth increased AUC to 0.80 (0.74-0.87) (p = 0.09) and AUC did not change with MetaboAge (0.76 (0.69-0.83) (p = 0.89)). Higher MetaboHealth and MetaboAge scores were associated with 1-year mortality. The addition of MetaboHealth to established clinical predictors only marginally improved mortality prediction in this cohort with various types of tumors. MetaboHealth may potentially improve identification of older patients vulnerable for adverse events, but numbers were too small for definitive conclusions. The TENT study is retrospectively registered at the Netherlands Trial Register (NTR), trial number NL8107. Date of registration: 22-10-2019.

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.

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

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

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.

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.

How to incorporate chronic health conditions in oncologic decision-making and care for older patients with cancer? A survey among healthcare professionals.

PURPOSE: A substantial proportion of patients with cancer are older and experience multimorbidity. As the population is ageing, the management of older patients with multimorbidity including cancer will represent a significant challenge to current clinical practice. METHODS: This study aimed to (1) identify which chronic health conditions may cause change in oncologic decision-making and care in older patients and (2) provide guidance on how to incorporate these in decision-making and care provision of older patients with cancer. Based on a scoping literature review, an initial list of prevalent morbidities was developed. A subsequent survey among healthcare providers involved in the care for older patients with cancer assessed which chronic health conditions were relevant and why. RESULTS: A list of 53 chronic health conditions was developed, of which 34 were considered likely or very likely to influence decision-making or care according to the 39 healthcare professionals who responded. These conditions were further categorized into five patient profiles. From these conditions, five patient profiles were developed, namely, (1) a somatic profile consisting of cardiovascular, metabolic, and pulmonary disease, (2) a functional profile, including conditions that cause disability, dependency or a high caregiver burden, (3) a psychosocial profile, including cognitive impairment, (4) a nutritional profile also including digestive system diseases, and finally, (5) a concurrent cancer profile. All profiles were considered likely to impact decision-making with differences between treatment modalities. The impact on the care trajectory was generally considered less significant, except for patients with care dependency and psychosocial health problems. CONCLUSIONS: Chronic health conditions have various ways of influencing oncologic decision-making and the care trajectory in older adults with cancer. Understanding why specific chronic health conditions may impact the oncologic care trajectory can aid clinicians in the management of older patients with multimorbidity, including cancer.

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.

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.

Self-reported electronic symptom monitoring in older patients with multimorbidity treated for cancer: Development of a core dataset based on expert consensus, literature review, and quality of life questionnaires.

INTRODUCTION: In cancer care, symptom monitoring during treatment results in improved clinical outcomes such as improved quality of life, longer survival, and fewer hospital admissions. However, as the majority of patients with cancer are older and have multimorbidity, they may benefit from monitoring of additional symptoms. The aim of this study was to identify a core set of symptoms to monitor in older patients with multimorbidity treated for cancer, including symptoms caused by treatment side effects, destabilization of comorbidities, and functional decline. MATERIALS AND METHODS: During a scoping literature search, 17 quality of life questionnaires were used to select 53 possible symptoms to monitor. An expert panel of cancer and geriatrics specialists was asked to participate in multiple online surveys to indicate whether these symptoms were not relevant to monitor, only relevant to monitor in a specific patient group, or relevant to monitor in all patients. In a subsequent round the list was reduced and the panel indicated how frequently these symptoms should be monitored during cancer treatment and after cancer treatment completion. Finally, a digital consensus meeting was organised to decide when symptoms had to trigger a recommendation to the patient to get in touch with their medical team. RESULTS: In total, 30 healthcare professionals participated in the online surveys. After two rounds, a dataset of 19 symptoms related to cancer, cancer treatment, functional decline, and destabilization of comorbidities was agreed upon for monitoring. Five symptoms were selected for daily monitoring during treatment, seven for weekly, and seven for monthly. After treatment completion, the panel agreed upon less frequent reporting. Additionally, nine symptoms to be monitored only in patients with specific cancer types or treatment types were chosen, such as "cough up blood" in lung cancer. DISCUSSION: This study is the first to identify a core set of symptoms to monitor in older patients with multimorbidity treated for cancer. Future research is needed to investigate whether the monitoring of these symptoms is feasible and improves clinical outcomes in older patients with multimorbidity treated for cancer.

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.

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.

Geriatric assessment for older people with cancer: policy recommendations.

Most cancers occur in older people and the burden in this age group is increasing. Over the past two decades the evidence on how best to treat this population has increased rapidly. However, implementation of new best practices has been slow and needs involvement of policymakers. This perspective paper explains why older people with cancer have different needs than the wider population. An overview is given of the recommended approach for older people with cancer and its benefits on clinical outcomes and cost-effectiveness. In older patients, the geriatric assessment (GA) is the gold standard to measure level of fitness and to determine treatment tolerability. The GA, with multiple domains of physical health, functional status, psychological health and socio-environmental factors, prevents initiation of inappropriate oncologic treatment and recommends geriatric interventions to optimize the patient's general health and thus resilience for receiving treatments. Multiple studies have proven its benefits such as reduced toxicity, better quality of life, better patient-centred communication and lower healthcare use. Although GA might require investment of time and resources, this is relatively small compared to the improved outcomes, possible cost-savings and compared to the large cost of oncologic treatments as a whole.

Survival of Patients With Cancer With DPYD Variant Alleles and Dose-Individualized Fluoropyrimidine Therapy-A Matched-Pair Analysis.

PURPOSE: DPYD-guided fluoropyrimidine dosing improves patient safety in carriers of DPYD variant alleles. However, the impact on treatment outcome in these patients is largely unknown. Therefore, progression-free survival (PFS) and overall survival (OS) were compared between DPYD variant carriers treated with a reduced dose and DPYD wild-type controls receiving a full fluoropyrimidine dose in a retrospective matched-pair survival analysis. METHODS: Data from a prospective multicenter study (ClinicalTrials.gov identifier: NCT02324452) in which DPYD variant carriers received a 25% (c.1236G>A and c.2846A>T) or 50% (DPYD*2A and c.1679T>G) reduced dose and data from DPYD variant carriers treated with a similarly reduced dose of fluoropyrimidines identified during routine clinical care were obtained. Each DPYD variant carrier was matched to three DPYD wild-type controls treated with a standard dose. Survival analyses were performed using Kaplan-Meier estimates and Cox regression. RESULTS: In total, 156 DPYD variant carriers and 775 DPYD wild-type controls were available for analysis. Sixty-one c.1236G>A, 25 DPYD*2A, 13 c.2846A>T, and-when pooled-93 DPYD variant carriers could each be matched to three unique DPYD wild-type controls. For pooled DPYD variant carriers, PFS (hazard ratio [HR], 1.23; 95% CI, 1.00 to 1.51; P = .053) and OS (HR, 0.95; 95% CI, 0.75 to 1.51; P = .698) were not negatively affected by DPYD-guided dose individualization. In the subgroup analyses, a shorter PFS (HR, 1.43; 95% CI, 1.10 to 1.86; P = .007) was found in c.1236G>A variant carriers, whereas no differences were found for DPYD*2A and c.2846A>T carriers. CONCLUSION: In this exploratory analysis, DPYD-guided fluoropyrimidine dosing does not negatively affect PFS and OS in pooled DPYD variant carriers. Close monitoring with early dose modifications based on toxicity is recommended, especially for c.1236G>A carriers receiving a reduced starting dose.