BackgroundPrevious studies have shown that survival outcomes for older patients with breast cancer vary substantially across Europe, with worse survival reported in the United Kingdom. It has been... Show moreBackgroundPrevious studies have shown that survival outcomes for older patients with breast cancer vary substantially across Europe, with worse survival reported in the United Kingdom. It has been hypothesised that these differences in survival outcomes could be related to treatment variation.ObjectivesWe aimed to compare patient and tumour characteristics, treatment selection and survival outcomes between two large prospective cohorts of older patients with operable breast cancer from the United Kingdom (UK) and The Netherlands.MethodsWomen diagnosed with operable breast cancer aged ≥70 years were included. A baseline comprehensive geriatric assessment was performed in both cohorts, with data collected on age, comorbidities, cognition, nutritional and functional status. Baseline tumour characteristics and treatment type were collected. Univariable and multivariable Cox regression models were used to compare overall survival between the cohorts.Results3262 patients from the UK Age Gap cohort and 618 patients from the Dutch Climb cohort were included, with median ages of 77.0 (IQR: 72.0–81.0) and 75.0 (IQR: 72.0–81.0) years, respectively. The cohorts were generally comparable, with slight differences in rates of comorbidity and frailty. Median follow-up for overall survival was 4.1 years (IQR 2.9–5.4) in Age Gap and 4.3 years (IQR 2.9–5.5) in Climb. In Age Gap, both the rates of primary endocrine therapy and adjuvant hormonal therapy after surgery were approximately twice those in Climb (16.6% versus 7.3%, p < 0.001 for primary endocrine therapy, and 62.2% versus 38.8%, p < 0.001 for adjuvant hormonal therapy). There was no evidence of a difference in overall survival between the cohorts (adjusted HR 0.94, 95% CI 0.74–1.17, p = 0.568).ConclusionsIn contrast to previous studies, this comparison of two large national prospective longitudinal multi-centre cohort studies demonstrated comparable survival outcomes between older patients with breast cancer treated in the UK and The Netherlands, despite differences in treatment allocation. Show less
Vlies, E. van der; Vernooij, L.M.; Erning, F.N. van; Vink, G.R.; Bos, W.J.W.; Portielje, J.E.A.; ... ; M. los 2021
Background: Surgery is the primary treatment for non-metastatic colorectal cancer (CRC) but is omitted in a proportion of older patients. Characteristics and prognosis of non-surgical patients are... Show moreBackground: Surgery is the primary treatment for non-metastatic colorectal cancer (CRC) but is omitted in a proportion of older patients. Characteristics and prognosis of non-surgical patients are largely unknown.Objective: To examine the characteristics and survival of surgical and non-surgical older patients with non-metastatic CRC in the Netherlands.Methods: All patients aged >= 70 years and diagnosed with non-metastatic CRC between 2014 and 2018 were identified in the Netherlands Cancer Registry. Patients were divided based on whether they underwent surgery or not. Three-year overall survival (OS) and relative survival (RS) were calculated for both groups separately. Relative survival and relative excess risks (RER) of death were used as measures for cancer-related survival.Results: In total, 987/20.423 (5%) colon cancer patients and 1.459/7.335 (20%) rectal cancer patients did not undergo surgery. Non-surgical treatment increased over time from 3.7% in 2014 to 4.8% in 2018 in colon cancer patients (P = 0.01) and from 17.1% to 20.2% in rectal cancer patients (P = 0.03). 3 year RS was 91% and 9% for surgical and non-surgical patients with colon cancer, respectively. For rectal cancer patients this was 93% and 37%, respectively. In surgical patients, advanced age (>= 80 years) did not decrease RS (colon; RER 0.9 (0.7-1.0), rectum; RER 0.9 (0.7-1.1)). In non-surgical rectal cancer patients, higher survival rates were observed in patients treated with chemoradiotherapy (OS 56%, RS 65%), or radiotherapy (OS 19%, RS 27%), compared to no treatment (OS 9%, RS 10%).Conclusion: Non-surgical treatment in older Dutch CRC patients has increased over time. Because survival of patients with colon cancer is very poor in the absence of surgery, this treatment decision must be carefully weighed. (Chemo-)radiotherapy may be a good alternative for rectal cancer surgery in older frail patients. (C) 2021 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Show less
Baltussen, J.C.; Welters, M.J.P.; Verdegaal, E.M.E.; Kapiteijn, E.; Schrader, A.M.R.; Slingerland, M.; ... ; Glas, N.A. de 2021
Simple Summary Immune checkpoint inhibitors (ICIs) have revolutionized treatment of advanced melanoma and survival of melanoma patients has radically improved since. However, as durable responses... Show moreSimple Summary Immune checkpoint inhibitors (ICIs) have revolutionized treatment of advanced melanoma and survival of melanoma patients has radically improved since. However, as durable responses after ICIs are only observed in 30-50% of melanoma patients, there is an unmet need to identify predictive biomarkers for response. This systematic review demonstrates the substantial number of publications that have studied a wide variety of possible biomarkers. Covering 177 publications that investigated 128 unique biomarkers, we provide an overview of all studied biomarkers in correlation with response or survival. We highlight blood, tumor and fecal biomarkers that were associated with response to ICIs in multiple studies. Of these, only T-cell inflamed gene expression profiling was predictive for response in a large clinical trial and validated in other studies, thus representing a promising biomarker for clinical practice. Large validation studies are warranted to confirm the predictive utility of other biomarkers, thereby further personalizing immunotherapy treatment. Immune checkpoint inhibitors (ICIs) have strongly improved the survival of melanoma patients. However, as durable response to ICIs are only seen in a minority, there is an unmet need to identify biomarkers that predict response. Therefore, we provide a systematic review that evaluates all biomarkers studied in association with outcomes of melanoma patients receiving ICIs. We searched Pubmed, COCHRANE Library, Embase, Emcare, and Web of Science for relevant articles that were published before June 2020 and studied blood, tumor, or fecal biomarkers that predicted response or survival in melanoma patients treated with ICIs. Of the 2536 identified reports, 177 were included in our review. Risk of bias was high in 40%, moderate in 50% and low in 10% of all studies. Biomarkers that correlated with response were myeloid-derived suppressor cells (MDSCs), circulating tumor cells (CTCs), CD8+ memory T-cells, T-cell receptor (TCR) diversity, tumor-infiltrating lymphocytes (TILs), gene expression profiling (GEP), and a favorable gut microbiome. This review shows that biomarkers for ICIs in melanoma patients are widely studied, but heterogeneity between studies is high, average sample sizes are low, and validation is often lacking. Future studies are needed to further investigate the predictive utility of some promising candidate biomarkers. Show less
Purpose Shared decision making calls for clinician communication strategies that aim to foster choice awareness and to present treatment options neutrally, such as by not showing a preference.... Show morePurpose Shared decision making calls for clinician communication strategies that aim to foster choice awareness and to present treatment options neutrally, such as by not showing a preference. Evidence for the effectiveness of these communication strategies to enhance patient involvement in treatment decision making is lacking. We tested the effects of 2 strategies in an online randomized video-vignettes experiment. Methods We developed disease-specific video vignettes for rheumatic disease, cancer, and kidney disease showcasing a physician presenting 2 treatment options. We tested the strategies in a 2 (choice awareness communication present/absent) by 2 (physician preference communication present/absent) randomized between-subjects design. We asked patients and disease-naive participants to view 1 video vignette while imagining being the patient and to report perceived room for involvement (primary outcome), understanding of treatment information, treatment preference, satisfaction with the consultation, and trust in the physician (secondary outcomes). Differences across experimental conditions were assessed using 2-way analyses of variance. Results A total of 324 patients and 360 disease-naive respondents participated (mean age, 52 +/- 14.7 y, 54% female, 56% lower educated, mean health literacy, 12 +/- 2.1 on a 3-15 scale). The results showed that choice awareness communication had a positive (M-present = 5.2 v. M-absent = 5.0, P = 0.042, eta(2)(partial) = 0.006) and physician preference communication had no (M-present = 5.0 v. M-absent = 5.1, P = 0.144, eta(2)(partial) = 0.003) significant effect on perceived room for involvement in decision making. Physician preference communication steered patients toward preferring that treatment option (M-present = 4.7 v. M-absent = 5.3, P = 0.006, eta(2)(partial) = 0.011). The strategies had no significant effect on understanding, satisfaction, or trust. Conclusions This is the first experimental evidence for a small effect of fostering choice awareness and no effect of physician preference on perceived room to participate in decision making. Physician preference steered patients toward preferring that option. Show less
Hulst, H.C. van der; Bastiaannet, E.; Portielje, J.E.A.; Bol, J.M. van der; Dekker, J.W.T. 2021
Introduction: Frail patients with colorectal cancer (CRC) are at increased risk of complications after surgery. Prehabilitation seems promising to improve this outcome and therefore we evaluated... Show moreIntroduction: Frail patients with colorectal cancer (CRC) are at increased risk of complications after surgery. Prehabilitation seems promising to improve this outcome and therefore we evaluated the effect of physical prehabilitation on postoperative complications in a retrospective cohort of frail CRC patients. Methods: The study consisted of all consecutive non-metastatic CRC patients >70 years who had elective surgery from 2014 to 2019 in a teaching hospital in the Netherlands, where a physical prehabilitation program was implemented from 2014 on. We performed both an intention-to-treat and per protocol analysis to evaluate postoperative complications in the physical prehabilitation (PhP) and non-prehabilitation (NP) group. Results: Eventually, 334 elective patients were included. The 124 (37.1%) patients in the PhP-group presented with higher age, higher comorbidity scores and walking-aid use compared to the NP-group. Medical complications occurred in 26.6% of the PhP-group and in 20.5% of the NP-group (p = 0.20) and surgical complications in 19.4% and 14.3% (p = 0.22) respectively. In all frailty subgroups, the medical complications were lower in the PhP-group compared to the NP-group (35.9% vs. 45.5% for patients with >2 comorbidities, 36.2% vs. 39.1% for ASA score > III, 29.2% vs. 45.8% for walking-aid use). Differences were not significant. Conclusions: In this study, patients selected for physical prehabilitation had a worse frailty profile and therefore a higher a priori risk of postoperative complications. However, the postoperative complication rate was not increased compared to patients who were less frail at baseline and without prehabilitation. Hence, physical prehabilitation may prevent postoperative complications in frail CRC patients >70 years. (c) 2021 Elsevier Ltd, BASO -The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Show less
Plas-Krijgsman, W.G. van der; Giardiello, D.; Putter, H.; Steyerberg, E.W.; Bastiaannet, E.; Stiggelbout, A.M.; ... ; Glas, N.A. de 2021
Background Current prediction tools for breast cancer outcomes are not tailored to the older patient, in whom competing risk strongly influences treatment effects. We aimed to develop and validate... Show moreBackground Current prediction tools for breast cancer outcomes are not tailored to the older patient, in whom competing risk strongly influences treatment effects. We aimed to develop and validate a prediction tool for 5-year recurrence, overall mortality, and other-cause mortality for older patients (aged >= 65 years) with early invasive breast cancer and to estimate individualised expected benefits of adjuvant systemic treatment.Methods We selected surgically treated patients with early invasive breast cancer (stage I-III) aged 65 years or older from the population-based FOCUS cohort in the Netherlands. We developed prediction models for 5-year recurrence, overall mortality, and other-cause mortality using cause-specific Cox proportional hazard models. External validation was performed in a Dutch Cancer registry cohort. Performance was evaluated with discrimination accuracy and calibration plots.Findings We included 2744 female patients in the development cohort and 13631 female patients in the validation cohort. Median age was 74.8 years (range 65-98) in the development cohort and 76.0 years (70-101) in the validation cohort. 5-year follow-up was complete for more than 99% of all patients. We observed 343 and 1462 recurrences, and 831 and 3594 deaths, of which 586 and 2565 were without recurrence, in the development and validation cohort, respectively. The area under the receiver-operating-characteristic curve at 5 years in the external dataset was 0.76 (95% CI 0.75-0.76) for overall mortality, 0.76 (0.76-0.77) for recurrence, and 0.75 (0.74-0.75) for other-cause mortality.Interpretation The PORTRET tool can accurately predict 5-year recurrence, overall mortality, and other-cause mortality in older patients with breast cancer. The tool can support shared decision making, especially since it provides individualised estimated benefits of adjuvant treatment. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd. Show less
Zanden, V. van der; Soolingen, N.J. van; Viddeleer, A.R.; Trum, J.W.; Amant, F.; Mourits, M.J.E.; ... ; Souwer, E.T.D. 2021
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,... Show moreObjective. To determine the predictive value of lumbar skeletal muscle mass and density for postoperative outcomes in older women with advanced stage ovarian cancer.Methods. A multicenter, retrospective cohort study was performed in women >= 70 years old receiving surgery for primary, advanced stage ovarian cancer. Skeletal muscle mass and density were assessed in axial CT slices on level L3. Low skeletal muscle mass was defined as skeletal muscle index < 38.50 cm(2)/m(2). Low skeletal muscle density was defined as one standard deviation below the mean (muscle attenuation < 22.55 Hounsfield Units). The primary outcome was any postoperative complication <-30 days after surgery. Secondary outcomes included severe complications, infections, delirium, prolonged hospital stay, discharge destination, discontinua-tion of adjuvant chemotherapy and mortality.Results. In analysis of 213 patients, preoperative low skeletal muscle density was associated with postopera-tive 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 infec-tious 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 pre-dictor 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. (C) 2021 The Author(s). Published by Elsevier Inc. Show less
Simple Summary The objective was to develop and internally validate a predictive model based on preoperative predictors, including geriatric characteristics, for severe postoperative complications... Show moreSimple Summary The objective was to develop and internally validate a predictive model based on preoperative predictors, including geriatric characteristics, for severe postoperative complications after elective surgery for stage I-III CRC in patients >= 70 years. Potential predictors included demographics, comorbidity, tumour location, activities of daily living (ADL), history of falls, malnutrition, risk factors for delirium, use of mobility aid and polypharmacy. The least absolute shrinkage and selection operator (LASSO) method was used for predictor selection and prediction model building. A geriatric model that included gender, previous DVT or pulmonary embolism, COPD/asthma/emphysema, rectal cancer, the use of a mobility aid, ADL assistance, previous delirium and polypharmacy showed satisfactory discrimination with an AUC of 0.69 (95% CI 0.73-0.64); the AUC for the optimism corrected model was 0.65. An eight-item colorectal geriatric model (GerCRC) was developed. After external validation, this risk model has the potential to be used for preoperative (shared) decision-making. Introduction Older patients have an increased risk of morbidity and mortality after colorectal cancer (CRC) surgery. Existing CRC surgical prediction models have not incorporated geriatric predictors, limiting applicability for preoperative decision-making. The objective was to develop and internally validate a predictive model based on preoperative predictors, including geriatric characteristics, for severe postoperative complications after elective surgery for stage I-III CRC in patients >= 70 years. Patients and Methods: A prospectively collected database contained 1088 consecutive patients from five Dutch hospitals (2014-2017) with 171 severe complications (16%). The least absolute shrinkage and selection operator (LASSO) method was used for predictor selection and prediction model building. Internal validation was done using bootstrapping. Results: A geriatric model that included gender, previous DVT or pulmonary embolism, COPD/asthma/emphysema, rectal cancer, the use of a mobility aid, ADL assistance, previous delirium and polypharmacy showed satisfactory discrimination with an AUC of 0.69 (95% CI 0.73-0.64); the AUC for the optimism corrected model was 0.65. Based on these predictors, the eight-item colorectal geriatric model (GerCRC) was developed. Conclusion: The GerCRC is the first prediction model specifically developed for older patients expected to undergo CRC surgery. Combining tumour- and patient-specific predictors, including geriatric predictors, improves outcome prediction in the heterogeneous older population. Show less
Plas-Krijgsman, W.G. van der; Boer, A.Z. de; Jong, P. de; Bastiaannet, E.; Bos, F. van den; Mooijaart, S.P.; ... ; Glas, N.A. de 2021
The number of older patients with breast cancer has increased due to the aging of the general population. The use of a geriatric assessment in this population has been advocated in many studies and... Show moreThe number of older patients with breast cancer has increased due to the aging of the general population. The use of a geriatric assessment in this population has been advocated in many studies and guidelines as it can be used to identify high risk populations for early mortality and toxicity. Additionally, geriatric parameters could predict relevant outcome measures. This systematic review summarizes all available evidence on predictive factors for various outcomes (disease-related and survival, toxicity, and patient-reported outcomes), with a special focus on geriatric parameters and patient-reported outcomes, in older patients with breast cancer. Studies were identified through systematic review of the literature published up to September 1st 2019 in the PubMed database and EMBASe. A total of 173 studies were included. Most studies investigated disease-related and survival outcomes (n = 123, 71%). Toxicity was investigated in 40 studies (23%) and a mere 15% (n = 26) investigated patient-reported outcomes. Various measures that can be derived from a geriatric assessment were predictive for survival endpoints. Furthermore, geriatric parameters were among the most frequently found predictors for toxicity and patient-reported outcomes. In conclusion, this study shows that geriatric parameters can predict survival, toxicity, and patient-reported outcomes in older patients with breast cancer. These findings can be used in daily clinical practice to identify patients at risk of early mortality, high risk of treatment toxicity or poor functional outcome after treatment. A minority of studies used relevant outcome measures for older patients, showing the need for studies that are tailored to the older population.(c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). Show less
Glas, N.A. de; Bastiaannet, E.; Bos, F. van den; Mooijaart, S.P.; Veldt, A.A.M. van der; Suijkerbuijk, K.P.M.; ... ; Kapiteijn, E.W. 2021
Simple Summary: Trials suggest no differences in immunotherapy treatment between older and younger patients, but mainly young patients with a good performance status were included in these trials.... Show moreSimple Summary: Trials suggest no differences in immunotherapy treatment between older and younger patients, but mainly young patients with a good performance status were included in these trials. The aim of this study was to describe the treatment patterns and outcomes of "real-world" older patients with metastatic melanoma. We included 2216 patients aged >= 65 years from the Dutch Melanoma Treatment Registry and described outcomes of immunotherapy. The study showed that responses and severe side effects did not differ from previously reported younger populations and randomized trials, even in the oldest patients and in patients with other diseases. However, patients aged >= 75 discontinued treatment due to toxicity more often, resulting in fewer treatment cycles. We therefore conclude that immunotherapy seems to have similar effects in older patients compared to younger patients, but the impact of less severe toxicity on quality of life should be further studied as older patients are more likely to discontinue treatment.Background: Previous trials suggest no differences in immunotherapy treatment between older and younger patients, but mainly young patients with a good performance status were included. The aim of this study was to describe the treatment patterns and outcomes of "real-world" older patients with metastatic melanoma and to identify predictors of outcome. Methods: We included patients aged >= 65 years with metastatic melanoma from the Dutch Melanoma Treatment Registry. We described the reasons for hospital admissions and treatment discontinuation. Additionally, we assessed predictors of toxicity and response using logistic regression models and survival using Cox regression models. Results: We included 2216 patients. Grade >= 3 toxicity was not associated with age, comorbidities or WHO status. Patients aged >= 75 discontinued treatment due to toxicity more often, resulting in fewer treatment cycles. Response rates were similar to previous trials (40.3% and 43.6% in patients aged 65-75 and >= 75, respectively, for anti-PD1 treatment) and did not decrease with age or comorbidity. Melanoma-specific survival was not affected by age or comorbidity. Conclusion: Response rates and toxicity outcomes of checkpoint inhibitors did not change with increasing age or comorbidity. However, the impact of grade I-II toxicity on quality of life deserves further study as older patients discontinue treatment more frequently. Show less
Boer, A.Z. de; Bastiaannet, E.; Putter, H.; Mheen, P.M.J. van de; Siesling, S.; Munck, L. de; ... ; Glas, N.A. de 2021
Simple SummarySelecting older patients for adjuvant breast cancer treatments is challenging as its benefits can be diminished by shorter life expectancies. In addition to age, comorbidity increases... Show moreSimple SummarySelecting older patients for adjuvant breast cancer treatments is challenging as its benefits can be diminished by shorter life expectancies. In addition to age, comorbidity increases the risk of dying from other causes than breast cancer. Available prediction tools have either not adjusted for individual comorbidities or have shown inaccurate predictions when a higher number of comorbidities are present. Up to now, an optimal comorbidity score to be used in prediction tools has not been established. Therefore, this study aimed to assess the predictive value of the Charlson comorbidity index for other-cause mortality and to compare these predictions with using a simple comorbidity count. We found that the Charlson index performed similarly as comorbidity count. The use of comorbidity count in the development of new prediction tools for older patients with breast cancer is recommended as its simplicity enhances the tool's applicability in clinical practice.Background: Individualized treatment in older patients with breast cancer can be improved by including comorbidity and other-cause mortality in prediction tools, as the other-cause mortality risk strongly increases with age. However, no optimal comorbidity score is established for this purpose. Therefore, this study aimed to compare the predictive value of the Charlson comorbidity index for other-cause mortality with the use of a simple comorbidity count and to assess the impact of frequently occurring comorbidities. Methods: Surgically treated patients with stages I-III breast cancer aged >= 70 years diagnosed between 2003 and 2009 were selected from the Netherlands Cancer Registry. Competing risk analysis was performed to associate 5-year other-cause mortality with the Charlson index, comorbidity count, and specific comorbidities. Discrimination and calibration were assessed. Results: Overall, 7511 patients were included. Twenty-nine percent had no comorbidities, and 59% had a Charlson score of 0. After five years, in 1974, patients had died (26%), of which 1450 patients without a distant recurrence (19%). Besides comorbidities included in the Charlson index, the psychiatric disease was strongly associated with other-cause mortality (sHR 2.44 (95%-CI 1.70-3.50)). The c-statistics of the Charlson index and comorbidity count were similar (0.65 (95%-CI 0.64-0.65) and 0.64 (95%-CI 0.64-0.65)). Conclusions: The predictive value of the Charlson index for 5-year other-cause mortality was similar to using comorbidity count. As it is easier to use in clinical practice, our findings indicate that comorbidity count can aid in improving individualizing treatment in older patients with breast cancer. Future studies should elicit whether geriatric parameters could improve prediction. Show less
Brokaar, E.J.; Bos, F. van den; Visser, L.E.; Portielje, J.E.A. 2021
Polypharmacy is common in older adults with cancer and deprescribing potentially inappropriate medications becomes very relevant when life expectancy decreases due to metastatic disease. Especially... Show morePolypharmacy is common in older adults with cancer and deprescribing potentially inappropriate medications becomes very relevant when life expectancy decreases due to metastatic disease. Especially preventive medications may no longer be beneficial, because they may decrease quality of life and reduction in morbidity and mortality may be futile. Although deprescribing of preventive medication is common in the last period of life, it is still unusual during active cancer treatment for advanced disease, although life expectancy is often limited to less than 1 to 2 years in that stage. We performed a systematic search of the literature in Pubmed and Embase on the discontinuation of commonly utilized groups of preventive medication and evaluated the evidence of potential benefits and harms in patients aged 65 years or older with cancer and a limited life expectancy (LLE). From 21 included studies, it can be concluded that deprescribing lipid lowering drugs, antihypertensive drugs, osteoporosis drugs and antihyperglycemic drugs is feasible in a considerable part of patients with a LLE. Discontinuation may be performed safely, without the occurrence of serious adverse events or decrease of survival. The only study that addressed quality of life after deprescribing showed that discontinuation of statins improves quality of life in patients with a LLE. Recurrence of symptoms requiring reintroduction occurred in 0-13% of patients on antihyperglycemic treatment and 8-60% of patients using antihypertensive drugs. In order to reduce pill burden and futile treatment clinicians should discuss deprescribing of preventive medication with older patients with advanced cancer and a LLE. Show less
Background: The addition of bevacizumab to chemotherapy conferred a modest progression-free survival (PFS) benefit in metastatic triple-negative breast cancer (mTNBC). However, no overall survival ... Show moreBackground: The addition of bevacizumab to chemotherapy conferred a modest progression-free survival (PFS) benefit in metastatic triple-negative breast cancer (mTNBC). However, no overall survival (OS) benefit has been reported. Also, its combination with carboplatin-cyclophosphamide (CC) has never been investigated. Methods: The Triple-B study is a multicenter, randomized phase IIb trial that aims to prospectively validate predictive biomarkers, including baseline plasma vascular endothelial growth factor receptor-2 (pVEGFR-2), for bevacizumab benefit. mTNBC patients were randomized between CC and paclitaxel (P) without or with bevacizumab (CC +/- B or P +/- B). Here we report on a preplanned safety and preliminary efficacy analysis after the first 12 patients had been treated with CC+B and on the predictive value of pVEGFR-2. Results: In 58 patients, the median follow-up was 22.1 months. Toxicity was manageable and consistent with what was known for each agent separately. There was a trend toward a prolonged PFS with bevacizumab compared to chemotherapy only (7.0 vs. 5.2 months; adjusted HR = 0.60; 95% CI 0.33-1.08; p = 0.09), but there was no effect on OS. In this small study, pVEGFR-2 concentration did not predict a bevacizumab PFS benefit. Both the intention-to-treat analysis and the per-protocol analysis did not yield a significant treatment-by-biomarker test for interaction (p(interaction) = 0.69). Conclusions:CC and CC+B are safe first-line regimens for mTNBC and the side effects are consistent with those known for each individual agent. pVEGFR-2 concentration did not predict a bevacizumab PFS benefit. Show less
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... Show moreBackground: 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 NL81 07. Date of registration: 22-10-2019. Show less
Zanden, V. van der; Soolingen, N.J. van; Viddeleer, A.R.; Trum, J.W.; Amant, F.; Mourits, M.J.E.; ... ; Munster, B.C. van 2021
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... Show morePurpose 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. Show less
Souwer, E.T.D.; Bastiaannet, E.; Steyerberg, E.W.; Dekker, J.W.T.; Bos, F. van den; Portielje, J.E.A. 2020
Background: An increasing number of patients with Colorectal Cancer (CRC) is 65 years or older. We aimed to systematically review existing clinical prediction models for postoperative outcomes of... Show moreBackground: An increasing number of patients with Colorectal Cancer (CRC) is 65 years or older. We aimed to systematically review existing clinical prediction models for postoperative outcomes of CRC surgery, study their performance in older patients and assess their potential for preoperative decision making.Methods: A systematic search in Pubmed and Embase for original studies of clinical prediction models for outcomes of CRC surgery. Bias and relevance for preoperative decision making with older patients were assessed using the CHARMS guidelines.Results: 26 prediction models from 25 publications were included. The average age of included patients ranged from 61 to 76. Two models were exclusively developed for 65 and older. Common outcomes were mortality (n = 10), anastomotic leakage (n = 7) and surgical site infections (n = 3). No prediction models for quality of life or physical functioning were identified. Age, gender and ASA score were common predictors; 12 studies included intraoperative predictors. For the majority of the models, bias for model development and performance was considered moderate to high.Conclusions: Prediction models are available that address mortality and surgical complications after CRC surgery. Most models suffer from methodological limitations, and their performance for older patients is uncertain. Models that contain intraoperative predictors are of limited use for preoperative decision making. Future research should address the predictive value of geriatric characteristics to improve the performance of prediction models for older patients. (C) 2020 The Authors. Published by Elsevier Ltd. Show less
Boer, A.Z. de; Water, W. van de; Bastiaannet, E.; Glas, N.A. de; Kiderlen, M.; Portielje, J.E.A.; Extermann, M. 2020
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... Show moreIntroduction 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. Theoncogeriatric cohortcomprised unselected patients from the Moffitt Cancer Center, and thestandard cohortpatients 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. Show less
