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

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

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

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

Time toxicity among older patients with cancer treated with palliative systemic therapy.

PURPOSE: The time toxicity of anticancer therapy, defined as days spent with healthcare contact during treatment, represents a critical but understudied outcome. This study aims to quantify time toxicity among older patients with cancer receiving palliative systemic treatment. METHODS: All patients aged ≥ 65 years with metastatic cancer receiving cytotoxic chemotherapy, immunotherapy, or targeted therapy at a single center in Mexico were selected from a prospective patient navigation cohort. Patients completed a baseline assessment, including the G8 screening and quality of life measures. Physical healthcare contact days within the first 6 months were extracted from medical records and divided by days alive during the same period. Beta regression models were used to identify predictors of time toxicity. RESULTS: We identified 158 older patients (median age 71 years); 86% received cytotoxic chemotherapy. Seventy-three percent had an impaired G8 score and were considered vulnerable/frail. Six-month overall survival was 74%. Within the first 6 months, patients spent a mean of 21% (95% confidence interval (CI) 19-23%) of days with healthcare contact. Concurrent radiotherapy (odds ratio (OR) 1.55; 95%CI 1.21-1.97), cytotoxic chemotherapy versus targeted therapy (OR 1.64; 95%CI 1.13-2.37), and an impaired G8 (OR 1.27; 95%CI 1.01-1.60) were associated with increased time toxicity. CONCLUSION: Older adults with metastatic cancer spend 1 in 5 days with healthcare contact during treatment, with a higher burden of time toxicity for patients receiving radiotherapy or cytotoxic chemotherapy and those with potential frailty. These findings underscore the importance of informing patients about their expected healthcare contact days within the context of a limited life expectancy.

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

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

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

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

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

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

Physical Function and Physical Activity in Older Breast Cancer Survivors: 5-Year Follow-Up from the Climb Every Mountain Study.

BACKGROUND: A decline in physical activity and the ability to perform activities of daily living (ADL) and instrumental activities of daily living (IADL) could interfere with independent living and quality of life in older patients, but may be prevented with tailored interventions. The aim of the current study was to assess changes in physical activity and ADL/IADL in the first 5 years after breast cancer diagnosis in a real-world cohort of older patients and to identify factors associated with physical decline. METHODS: Patients aged ≥70 years with in situ or stages I-III breast cancer were included in the prospective Climb Every Mountain cohort study. Linear mixed models were used to assess physical activity (according to Metabolic Equivalent of Task (MET) hours per week) and ADL/IADL (according to the Groningen Activity Restriction Scale (GARS)) over time. Secondly, the association with geriatric characteristics, treatment, quality of life, depression, apathy, and loneliness was analyzed. RESULTS: A total of 239 patients were included. Physical activity and ADL/IADL changed in the first 5 years after diagnosis (mean change from baseline -11.6 and +4.2, respectively). Geriatric characteristics at baseline were strongly associated with longitudinal change in physical activity and ADL/IADL, whereas breast cancer treatment was not. A better quality of life was associated with better physical activity and preservation of ADL/IADL, while depression and loneliness were negatively associated with these outcomes. DISCUSSION: Geriatric characteristics, loneliness, and depressive symptoms were associated with physical decline in older patients with breast cancer, while breast cancer treatment was not.

A text-mining approach to study the real-world effectiveness and potentially fatal immune-related adverse events of PD-1 and PD-L1 inhibitors in older patients with stage III/IV non-small cell lung cancer.

BACKGROUND: This study was designed to investigate the impact of age on the effectiveness and immune-related adverse events (irAEs) of programmed death-(ligand)1 [PD-(L)1] inhibitors in patients with non-small cell lung cancer (NSCLC) using a novel text-mining technique. METHODS: This retrospective study included patients with stage III/IV NSCLC treated with a PD-(L)1 inhibitor (nivolumab, pembrolizumab, atezolizumab and durvalumab) at Leiden University Medical Centre and Haga Teaching hospital, (both in The Netherlands) from September 2016 to May 2021. All the relevant data was extracted from the structured and unstructured fields of the Electronic Health Records using a novel text-mining tool. Effectiveness [progression-free survival (PFS) and overall survival (OS)] and safety (the incidence of nine potentially fatal irAEs and systemic corticosteroid requirement) outcomes were compared across age subgroups (young: < 65 years, Middle-aged: 65-74 years, and old: ≥ 75 years) after adjustment for confounding. RESULTS: Of 689 patients, 310 patients (45.0%) were < 65 years, 275 patients (39.9%) were aged between 65 and 74 years, and 104 patients (15.1%) were ≥ 75 years. There was no significant difference between younger and older patients regarding PFS (median PFS 12, 8, 13 months respectively; Hazard ratio (HR)middle-aged = 1.14, 95% CI 0.92-1.41; HRold = 1.10, 95% CI 0.78-1.42). This was also the case for OS (median OS 19, 14, 18 months respectively; HRmiddle-aged = 1.22, 95% CI 0.96-1.53; HRold = 1.10, 95% CI 0.79-1.52). Safety analysis demonstrated a higher incidence of pneumonitis among patients aged 65-74. When all the investigated irAEs were pooled, there was no statistically significant difference found between age and the incidence of potentially fatal irAEs. CONCLUSIONS: The use of PD-(L)1 inhibitors is not associated with age related decrease of PFS and OS, nor with increased incidence of serious irAEs compared to younger patients receiving these treatments. Chronological age must therefore not be used as a predictor for the effectiveness or safety of ICIs.

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

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

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

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

Response to neoadjuvant chemotherapy and survival in molecular subtypes of resectable gastric cancer: a post hoc analysis of the D1/D2 and CRITICS trials.

BACKGROUND: Epstein-Barr virus positivity (EBV+) and microsatellite instability (MSI-high) are positive prognostic factors for survival in resectable gastric cancer (GC). However, benefit of perioperative treatment in patients with MSI-high tumors remains topic of discussion. Here, we present the clinicopathological outcomes of patients with EBV+, MSI-high, and EBV-/MSS GCs who received either surgery only or perioperative treatment. METHODS: EBV and MSI status were determined on tumor samples collected from 447 patients treated with surgery only in the D1/D2 trial, and from 451 patients treated perioperatively in the CRITICS trial. Results were correlated to histopathological response, morphological tumor characteristics, and survival. RESULTS: In the D1/D2 trial, 5-year cancer-related survival was 65.2% in 47 patients with EBV+, 56.7% in 47 patients with MSI-high, and 47.6% in 353 patients with EBV-/MSS tumors. In the CRITICS trial, 5-year cancer-related survival was 69.8% in 25 patients with EBV+, 51.7% in 27 patients with MSI-high, and 38.6% in 402 patients with EBV-/MSS tumors. Interestingly, all three MSI-high tumors with moderate to complete histopathological response (3/27, 11.1%) had substantial mucinous differentiation. No EBV+ tumors had a mucinous phenotype. 115/402 (28.6%) of EBV-/MSS tumors had moderate to complete histopathological response, of which 23/115 (20.0%) had a mucinous phenotype. CONCLUSIONS: In resectable GC, MSI-high had favorable outcome compared to EBV-/MSS, both in patients treated with surgery only, and in those treated with perioperative chemo(radio)therapy. Substantial histopathological response was restricted to mucinous MSI-high tumors. The mucinous phenotype might be a relevant parameter in future clinical trials for MSI-high patients.

Symptoms of anxiety but not depression before start of taxane-based chemotherapy are associated with peripheral neuropathy: a multicenter study in women with breast cancer.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy, especially after taxane-based therapy. This study aimed to examine the relationship between symptoms of anxiety and depression before the start of taxane-based chemotherapy and the development of CIPN in women with breast cancer. METHODS: In this prospective study, women with breast cancer receiving taxane-based (neo)adjuvant chemotherapy were recruited from four hospitals in the Netherlands. Patients completed questionnaires assessing anxiety and depressive symptoms before treatment and CIPN before treatment (T0), 6 weeks after start of treatment (T1), after the last cycle of chemotherapy (T2), and 6 months after the end of treatment (T3). Mixed model analyses were used to investigate whether medium/high levels of anxiety or depression at baseline are associated with the level of CIPN during and after treatment. RESULTS: Among the 61 participating women, 14 (23%) reported medium/high levels of anxiety and 29 (47.5%) reported medium/high levels of depressive symptoms at baseline. The group of women with medium/high baseline levels of anxiety showed a significantly higher increase in CIPN during and after chemotherapy than women with low baseline levels of anxiety (p < .001). No relationship between depressive symptoms at baseline and the development of CIPN was found. CONCLUSION: This study showed that baseline medium to high levels of anxiety but not depressive symptoms impacted the development of CIPN during and in the 6 months after treatment.

Testing the effects on information use by older versus younger women of modality and narration style in a hospital report card.

BACKGROUND: Hospital report cards (HRCs) are usually presented in a textual and factual format, likely hampering information processing. OBJECTIVE: This study aimed to investigate the effects of audiovisual and narrative information in HRCs on user responses, and to test differences between older and younger women. DESIGN: A 2 (modality [textual vs. audiovisual]) × 3 (narration style [factual vs. process narrative vs. experience narrative]) online experiment was conducted. Information about breast cancer care was used as a case example. Age (younger [<65] vs. older [≥65]) was included as a potential effect modifier. SETTING AND PARTICIPANTS: A total of 631 disease-naïve women (Mage = 56.06) completed an online survey. The outcomes were perceived cognitive load, satisfaction, comprehension, information recall and decisional conflict. Data were analysed using AN(C)OVAs. RESULTS: Audiovisual (vs. textual) information resulted in higher information satisfaction across age groups, but was associated with lower comprehension in older women. An experience narrative (vs. factual information) increased satisfaction with attractiveness and emotional support of the information only in older women. A three-way interaction effect was found, suggesting that older women were most satisfied with the comprehensibility of audiovisual factual or textual process narrative information. Younger women were most satisfied with the comprehensibility of audiovisual process narrative or textual factual information. DISCUSSION AND CONCLUSION: Audiovisual and narrative information in an HRC showed beneficial effects on satisfaction measures. In particular, audiovisual information could be incorporated into HRCs to increase satisfaction with information. PUBLIC CONTRIBUTION: Lay persons helped in optimizing the visuals used in the stimulus materials by checking for clarity.

Quality of life and illness perceptions in patients with breast cancer using a fasting mimicking diet as an adjunct to neoadjuvant chemotherapy in the phase 2 DIRECT (BOOG 2013-14) trial.

PURPOSE: In the phase II DIRECT study a fasting mimicking diet (FMD) improved the clinical response to neoadjuvant chemotherapy as compared to a regular diet. Quality of Life (QoL) and illness perceptions regarding the possible side effects of chemotherapy and the FMD were secondary outcomes of the trial. METHODS: 131 patients with HER2-negative stage II/III breast cancer were recruited, of whom 129 were randomly assigned (1:1) to receive either a fasting mimicking diet (FMD) or their regular diet for 3 days prior to and the day of neoadjuvant chemotherapy. The European Organisation for Research and Treatment of Cancer (EORTC) questionnaires EORTC-QLQ-C30 and EORTC-QLQ-BR23; the Brief Illness Perception Questionnaire (BIPQ) and the Distress Thermometer were used to assess these outcomes at baseline, halfway chemotherapy, before the last cycle of chemotherapy and 6 months after surgery. RESULTS: Overall QoL and distress scores declined during treatment in both arms and returned to baseline values 6 months after surgery. However, patients' perceptions differed slightly over time. In particular, patients receiving the FMD were less concerned and had better understanding of the possible adverse effects of their treatment in comparison with patients on a regular diet. Per-protocol analyses yielded better emotional, physical, role, cognitive and social functioning scores as well as lower fatigue, nausea and insomnia symptom scores for patients adherent to the FMD in comparison with non-adherent patients and patients on their regular diet. CONCLUSIONS: FMD as an adjunct to neoadjuvant chemotherapy appears to improve certain QoL and illness perception domains in patients with HER2-negative breast cancer. Trialregister ClinicalTrials.gov Identifier: NCT02126449.

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

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

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

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

Impact of Older Age and Comorbidity on Locoregional and Distant Breast Cancer Recurrence: A Large Population-Based Study.

BACKGROUND: Studies have demonstrated worse breast cancer-specific mortality with older age, despite an increasing risk of dying from other causes due to comorbidity (competing mortality). However, findings on the association between older age and recurrence risk are inconsistent. The aim of this study was to assess incidences of locoregional and distant recurrence by age, taking competing mortality into account. MATERIALS AND METHODS: Patients surgically treated for nonmetastasized breast cancer between 2003 and 2009 were selected from The Netherlands Cancer Registry. Cumulative incidences of recurrence were calculated considering death without distant recurrence as competing event. Fine and Gray analyses were performed to characterize the impact of age (70-74 [reference group], 75-79, and ≥80 years) on recurrence risk. RESULTS: A total of 18,419 patients were included. Nine-year cumulative incidences of locoregional recurrence were 2.5%, 3.1%, and 2.9% in patients aged 70-74, 75-79, and ≥80 years, and 9-year cumulative incidences of distant recurrence were 10.9%, 15.9%, and 12.7%, respectively. After adjustment for tumor and treatment characteristics, age was not associated with locoregional recurrence risk. For distant recurrence, patients aged 75-79 years remained at higher risk after adjustment for tumor and treatment characteristics (75-79 years subdistribution hazard ratio [sHR], 1.25; 95% confidence interval [CI], 1.11-1.41; ≥80 years sHR, 1.03; 95% CI, 0.91-1.17). CONCLUSION: Patients aged 75-79 years had a higher risk of distant recurrence than patients aged 70-74 years, despite the higher competing mortality. Individualizing treatment by using prediction tools that include competing mortality could improve outcome for older patients with breast cancer. IMPLICATIONS FOR PRACTICE: In this population-based study of 18,419 surgically treated patients aged 70 years or older, patients aged 75-79 years were at higher risk of distant recurrence than were patients aged 70-74 years. This finding suggests that patients in this age category are undertreated. In contrast, it was also demonstrated that the risk of dying without a recurrence strongly increases with age, and patients with a high competing mortality risk are easily overtreated. To identify older patients who may benefit from more treatment, clinicians should therefore take competing mortality risk into account. Prediction tools could facilitate this and thereby improve treatment strategy.

Early stage breast cancer treatment and outcome of older patients treated in an oncogeriatric care and a standard care setting: an international comparison.

INTRODUCTION: Since older patients with breast cancer are underrepresented in clinical trials, an oncogeriatric approach is advocated to guide treatment decisions. However, the effect on outcomes is unclear. The aim of this study was to compare treatments and outcomes between patients treated in an oncogeriatric and a standard care setting. METHODS: Patients aged ≥ 70 years with early stage breast cancer were included. The oncogeriatric cohort comprised unselected patients from the Moffitt Cancer Center, and the standard cohort patients from a Dutch population-based cohort. Cox models were used to characterize the influence of care setting on recurrence risk and overall mortality. RESULTS: Overall, 268 patients were included in the oncogeriatric and 1932 patients in the standard cohort. Patients in the oncogeriatric cohort were slightly younger, had more comorbidity, and received more adjuvant endocrine therapy and chemotherapy. Oncogeriatric care was associated with a lower risk of recurrence, which remained significant after adjustment for patient and tumour characteristics [hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.44-0.99]. Oncogeriatric care was also associated with a lower overall mortality, which also remained significant after adjustment for patient and tumour characteristics (HR 0.69, 95% CI 0.55-0.87). CONCLUSIONS: Patients treated in the oncogeriatric care setting had a lower risk of recurrence, which may be explained by more systemic treatment. Overall mortality was also lower, but other explanations besides care setting could not be ruled out as the cohorts had different patient profiles. Future studies need to clarify the impact of an oncogeriatric approach on outcomes.

Impact of Comorbidities and Age on Cause-Specific Mortality in Postmenopausal Patients with Breast Cancer.

BACKGROUND: The aim was to study the impact of comorbidities and age on breast cancer mortality, taking into account competing causes of death. SUBJECTS, MATERIALS, AND METHODS: Cohort analysis of Dutch and Belgian patients with postmenopausal, early hormone receptor-positive breast cancer included in the Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial between 2001 and 2006. This is a randomized controlled trial of patients who had completed local treatment with curative intent and were randomized to receive exemestane for 5 years, or sequential treatment of tamoxifen followed by exemestane for a duration of 5 years. Patients were categorized by number of comorbidities (no comorbidities, 1-2 comorbidities, and >2 comorbidities) and age (<70 years and ≥70 years). Main outcome was breast cancer mortality considering other-cause mortality as competing event; cumulative incidences were calculated using the Cumulative Incidence Competing Risk Methods, and the Fine and Gray model was used to calculate the effect of age and comorbidities for the cause-specific incidences of breast cancer death, taking into account the effect of competing causes of death. RESULTS: Overall, 3,159 patients were included, of which 2,203 (69.7%) were aged <70 years and 956 (30.3%) were aged ≥70 years at diagnosis. Cumulative incidence of breast cancer mortality was higher among patients ≥70 without comorbidities (22.2%, 95% CI, 17.5-26.9) compared with patients <70 without comorbidities (15.6%, 95% CI, 13.6-17.7, reference group), multivariable subdistribution hazard ratio (sHR) 1.49 (95% CI, 1.12-1.97, p = .005) after a median follow-up of 10 years. Use of chemotherapy was lower in older patients (1%, irrespective of the number of comorbidities) compared with younger patients (50%, 44%, and 38% for patients with no, 1-2, or >2 comorbidities, p < .001). CONCLUSION: Older patients without comorbidities have a higher risk of dying due to breast cancer than younger counterparts, even when taking into account higher competing mortality, while use of chemotherapy in this group was low. These findings underline the need to take into account comorbidities, age, and competing mortality in the prognosis of breast cancer for accurate decision making. IMPLICATIONS FOR PRACTICE: Older patients without comorbidity are at increased risk of dying from breast cancer, despite a higher other-cause mortality. This study shows that including age and comorbidity for the assessment of breast cancer mortality and other-cause mortality is indispensable for treatment decision making in older patients. Future prognostic tools for breast cancer prognosis should incorporate these items as well as risk of toxicity of adjuvant chemotherapy to adequately predict outcomes to optimize personalized treatment for older patients with early breast cancer.

Improved survival of older patients with advanced breast cancer due to an increase in systemic treatments: a population-based study.

PURPOSE: The number of older patients with breast cancer is rapidly increasing. A previous study showed that between 1990 and 2005, the survival of older patients with breast cancer did not improve in contrast to younger patients. In recent years, scientific evidence in the older age group has increased and specific guidelines for older women with breast cancer have been developed. The aim of this study was to assess changes in survival outcomes of older patients with breast cancer. PATIENTS AND METHODS: All patients with breast cancer between 2000 and 2017 were included from the Netherlands cancer registry. We assessed changes in treatments using logistic regression. We calculated changes in relative survival as proxy for breast cancer mortality, stratified by age and stage. RESULTS: We included 239,992 patients. Relative survival improved for patients < 65 for all stages. In patients aged 65-75 years, relative survival did not improve in stage I-II but did improve in stage III breast cancer (RER 0.98, 95% CI 0.96-1.00, p = 0.046). Concurrently, prescription of systemic treatments increased. In patients > 75, relative survival did not improve in patients with stage I/II or stage III disease, nor did treatment strategies change. CONCLUSIONS: This study shows that relative survival of patients aged 65-75 years with advanced breast cancer has improved, and concurrently, prescription of systemic treatment increased. To improve survival of patients > 75 as well, future studies should focus on individualizing treatments based on concomitant comorbidity, geriatric parameters and the risk of competing mortality and toxicity of treatments.