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Background: The Dutch Committee for the Evaluation of Oncological Agents (cieBOM) assesses the clinical benefit of systemic anti-cancer treatments (SACTs). For SACTs tested in non-randomized trials (NRTs), cieBOM primarily utilizes response-related thresholds as assessment criteria. As sufficiency of NRT-based evidence for benefit assessments is questionable, this study investigated whether and how NRTs can be used to assess the clinical benefit of new SACTs initially appraised by cieBOM based on randomized controlled trials (RCTs)., Methods: Using the RCTs underpinning cieBOM recommendations issued between 2015 and 2017, we searched for matching NRTs and applied the NRT-related assessment criteria by cieBOM to them. We then compared the assessment outcomes to the respective RCT-based cieBOM recommendations. Further, we investigated how the assessments would change when applying different response-related thresholds and adding a progression-free survival (PFS) threshold., Results: For 13 of the 37 eligible recommendations, a matching NRT was found. Two treatments were assessed positively and six negatively; five treatments were non-assessable. Two positive recommendations matched a positive NRT-based assessment; one matching negative assessment was found, and one treatment could not be assessed based on either trial results. Adding a > 6 months PFS threshold decreased the number of non-assessable NRTs (five to two)., Conclusions: Limited publications and inconsistent data reporting hampered the viability of NRTs for clinical benefit assessments of SACTs beyond the scope of rare indications. Further, response-related assessment criteria alone might not fully grasp the clinical benefit of novel SACTs. NRT-based assessments should be considered with caution due to uncertainty of the trial results., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Patients with testicular cancer treated with chemotherapy have an increased risk of developing early cardiovascular events. Identification of patients with testicular cancer at a high risk of these events enables the development of preventative strategies. This study validates the vascular fingerprint tool to identify these patients., Patients and Methods: We carried out a multicenter prospective study in patients with metastatic testicular cancer [International Germ Cell Cancer Collaborative Group (IGCCCG) good or intermediate risk; retroperitoneal mass <5 cm]. In eligible patients, the vascular fingerprint was assessed before the start of cisplatin-based chemotherapy, which consists of five risk factors, namely, smoking, overweight (body mass index >25 kg/m 2 ), hypertension (blood pressure >140/90 mmHg), dyslipidemia (fasting cholesterol >5.1 mmol/l or low-density lipoprotein-cholesterol >2.5 mmol/l), and diabetes mellitus (fasting glucose ≥7.0 mmol/l). The presence of three or more risk factors was defined as high-risk vascular fingerprints. A log-rank test was carried out with a cardiovascular event within 1 year after the start of chemotherapy as the primary endpoint., Results: A total of 196 patients with metastatic testicular cancer were included; 15 patients (8%) developed a cardiovascular event: 4 (2%) arterial events and 11 (6%) venous thrombotic events. Overall, 189 vascular fingerprint scores were available. Patients with a high-risk vascular fingerprint (62/189) had a higher risk of developing a cardiovascular event (hazard ratio 3.27, 95% confidence interval 1.16-9.18; log-rank: P = 0.017). Histological diagnosis, prognosis group, cumulative chemotherapy dose, and retroperitoneal mass size did not differ between patients with or without a cardiovascular event. All patients with an arterial event had a high-risk vascular fingerprint compared with 5/11 patients with a venous event. Overweight was more prevalent in patients with cardiovascular events (87% versus 59%; P = 0.037)., Conclusions: The vascular fingerprint is a validated tool to identify patients with testicular cancer at a high risk of developing early cardiovascular events. This tool can be used to develop preventative strategies with anticoagulant treatment., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In the Netherlands, the clinical benefit of systemic anti-cancer treatments (SACTs) is assessed by the Committee for the Evaluation of Oncological Agents (cieBOM). For non-curative SACTs, the assessment is based on the hazard ratio (HR) for progression-free survival and/or overall survival (OS), and the difference in median survival. We evaluated the impact of different thresholds for effectiveness by reassessing the clinical benefit of SACTs., Methods: We reassessed SACTs that were initially assessed by cieBOM between 2015 and 2017. Four scenarios were formulated: replacing an "OR" approach (initial assessment) by an "AND" approach (used in all scenarios), changing the HR threshold from < 0.70 (initial assessment) to < 0.60, changing the threshold for the difference in median survival from > 12 weeks (initial assessment) to > 16 weeks, and including thresholds for OS rates. The outcomes of these scenarios were compared to the outcomes of the initial assessment., Results: Reassessments were conducted for 41 treatments. Replacing the "OR" approach by an "AND" approach substantially decreased the number of positive assessments (from 33 to 22), predominantly affecting immunotherapies. This number further decreased (to 21 and 19, respectively) in case more restrictive thresholds for the HR and difference in median survival were used. Including thresholds for OS rates slightly mitigated the impact of applying an "AND" approach., Conclusions: The scenario-specific thresholds had a substantial impact; the number of negative assessments more than doubled. Since this was not limited to treatments with marginal survival benefits, understanding the potential challenges that may arise from applying more restrictive thresholds is essential., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The study objective was to assess the feasibility of the Patient Benefit Assessment Scale (P-BAS), a digital tool designed to enable older outpatients (≥70 years) to elucidate at home their individual goals regarding their current medical issue. Several digital tools are developed to assist older people in identifying their goals, thereby facilitating the process of shared decision making. However, studies on the feasibility of these digital tools, especially in older patients, are limited. Data were collected from 36 older patients. The study comprised three stages. In stage I and II, cognitive interviews were conducted to strengthen the feasibility of the P-BAS. In stage III, 80% of the patients completed the P-BAS independently at home. The cognitive interviews provided insight into patients' interpretation and individual understanding of the digital visual P-BAS and associated opportunities for improvement, which were subsequently implemented. One conclusion is that the digital visual P-BAS might be of added value for patients and contributes to the process of shared decision making, assuring that the goals of the patient will be into account in treatment options. Findings are useful for researchers interested in technological tools that contribute to shared decision making., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: The number of people with cancer will increase in the Netherlands. Further concentration and network care is pursued. The aim of this study was to explore how long medical oncology patients are willing to travel for their cancer care., Method: A flashmob study into patients' willingness to travel for cancer care was conducted in 65 Dutch hospitals. Patients completed a questionnaire about willingness to travel and any experienced issues with traveling., Results: A total of 4337 medical oncology patients completed the questionnaire. Of the patients, 20% were willing to travel more than 1 hour (one-way) for their current treatment, and more willing to travel for treatment in a hospital more experienced in their specific type of cancer (44% more than 1 hour). Willingness to travel longer was higher among patientsagedv40 years or younger, those with higher education, with better physical functioning and with a rare cancer. Willingness to travel longer was lowest among patients aged 75 or older. Approximately 30% of all patients experienced issues with traveling, especially those with comorbidities or with decreased physical functioning., Conclusion: In this flashmob study, 15% of patients were willing to travel up to 30 minutes (one-way) and 44% more than 1 hour for treatment and follow-up in a hospital more experienced in their specific type of cancer. Patients aged 75 years or older were less willing to travel longer. Thirty percent of patients experienced issues with travelling. It is important to take this into account in the future organization of cancer care.

As the number of cancer patients increases and new (mostly expensive) treatment options are evolving rapidly, a critical evaluation of the value of new treatments is required in order to maintain access to new drugs and affordable cancer care. In the Netherlands, the Dutch Society of Medical Oncology- CieBOM (NVMO CieBOM) has an unique role in assessment of the value and use of new oncological drugs, next to the National Committee of Health Insurance (cieBAG) and the Dutch Health Care Institute. CieBOM developed transparent criteria for approval of oncological drugs in several settings, and recently also criteria for drugs only tested in non-randomised studies have been developed.

Purpose: Guidelines recommend endocrine treatment for estrogen receptor-positive (ER+) breast cancers for up to 10 years. Earlier data suggest that the 70-gene signature (MammaPrint) has potential to select patients that have an excellent survival without chemotherapy and limited or no tamoxifen treatment. The aim was to validate the 70-gene signature ultralow-risk classification for endocrine therapy decision making., Methods: In the IKA trial, postmenopausal patients with non-metastatic breast cancer had been randomized between no or limited adjuvant tamoxifen treatment without receiving chemotherapy. For this secondary analysis, FFPE tumor material was obtained of ER+HER2- patients with 0-3 positive lymph nodes and tested for the 70-gene signature. Distant recurrence-free interval (DRFI) long-term follow-up data were collected. Kaplan-Meier curves were used to estimate DRFI, stratified by lymph node status, for the three predefined 70-gene signature risk groups., Results: A reliable 70-gene signature could be obtained for 135 patients. Of the node-negative and node-positive patients, respectively, 20% and 13% had an ultralow-risk classification. No DRFI events were observed for node-negative patients with an ultralow-risk score in the first 10 years. The 10-year DRFI was 90% and 66% in the low-risk (but not ultralow) and high-risk classified node-negative patients, respectively., Conclusion: These survival analyses indicate that the postmenopausal node-negative ER+HER2- patients with an ultralow-risk 70-gene signature score have an excellent 10-year DRFI after surgery with a median of 1 year of endocrine treatment. This is in line with published results of the STO-3-randomized clinical trial and supports the concept that it is possible to reduce the duration of endocrine treatment in selected patients., (© 2022. The Author(s).)

Competing Interests: EFS reports grants form AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Bayer, Merck Sharp & Dphme, Eli Lilly, Daiichi Sankyo, Roche, Novartis, Takeda, Pharmamar; received consulting fees from Eli Lilly; and received payments or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events for Boehringer Ingelheim, AstraZeneca, Daiichi Sankyo, and Novartis, all outside the submitted work. EEV reports grants from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis Oncology, GlaxoSmithKline, Merck Sharp & Dohme, Novartis , Pfizer, Roche, and Sanofi, all outside the submitted work. All other authors declare no competing interests. The DRUG Access Protocol is supported by all participating pharmaceutical companies: Bayer, Roche, and Sanofi. No company had a role in writing of the manuscript or decision to submit it for publication. EEV, HJB, and EFS led the DRUG Access Protocol trial as principal investigators. HG and HMWV functioned as co-principal investigators for the trial. LJZ and SBvWvD-K wrote the manuscript. LJZ, GFdW, and BSG coordinated the trial. SBvWvD-K and AAMGP-vR functioned as representatives on behalf of the health insurance companies during trial design. LT, THLT, and JEdB represented the Dutch National Health Care Institute during trial design. NB, ANMW, FALME, and EFS functioned as representatives of the Dutch Medical Societies for Oncology, Pulmonology and Haematology during trial design. LJZ and SBvWvD-K contributed equally as first authors.

Purpose: Evidence-based guidelines on how to prevent or treat cetuximab-related skin reactions are lacking and multiple care and management strategies are used. The main purpose of the present study is to gain information about the different skincare products being used against skin reactions in metastatic colorectal cancer (mCRC) and recurrent/metastatic (R/M) or locally advanced (LA) squamous cell cancer of the head and neck (SCCHN) patients treated with cetuximab., Methods: An open-label, prospective observational study conducted in the Netherlands. The occurrence of skin reactions and the care and management options taken were documented for 16 weeks, starting from the first administration of cetuximab., Results: A total of 103 patients were included in 7 hospitals. 38 patients (37%) developed a grade ≥ 2 skin reaction. Eighty-six patients could be analysed for the primary endpoint (73.3% males, mean age 62.4 years, n = 44 LA SCCHN, n = 16 R/M SCCHN, n = 26 mCRC). The most frequently used skin products at some point during the observation period were moisturizing products (70%), systemic antibiotics (64%), topical antibiotics (58%), lipid-regenerating (28%) and other topical products (28%). The overall use of products gradually increased from baseline to week 6-10, reducing by week 16. Hospital protocols were the primary reason (> 50%) for choice of the skincare products and medications., Conclusion: A variety of skin care products and antibiotics were commonly used. Only few patients developed severe cutaneous reactions. For patients, the occurrence of skin reactions did not influence their willingness to continue cetuximab therapy.

Introduction: Caring for a significant other during cancer treatment can be demanding. Little is known about the well-being of informal caregivers of patients with colon cancer. This study aims to examine informal caregiver well-being during adjuvant chemotherapy for colon cancer., Material and Methods: This exploratory longitudinal, prospective study measured the course of informal caregiver burden (Self-Perceived Pressure of Informal Care), distress (Hospital Anxiety and Depression Scale), health-related quality of life (RAND-36), marital satisfaction (Maudsley Marital Questionnaire), social support (Social Support List - Discrepancies), fatigue (Abbreviated Fatigue Questionnaire), and self-esteem (Caregiver Reaction Assessment) before (T0), during (T1), and after (T2) patients' treatment., Results: Baseline data of 60 out of 76 eligible dyads (79%) were analyzed. Mean levels of informal caregiver burden and distress improved significantly over time, as did their health-related quality of life and perceived social support. At baseline, 30% and 26.7% of informal caregivers reported moderate-to-high levels of burden and clinically relevant levels of distress, respectively, which changed to 20% and 18.8% at T2. Informal caregiver burden and distress at baseline were the strongest predictors of informal caregiver burden and distress during and following patients' treatment, respectively., Conclusion: When informal caregivers and patients experience problems before start of adjuvant chemotherapy, problems seem to improve over time. Approximately 20% of informal caregivers remain burdened and distressed after patients' end of treatment. Paying attention to baseline distress and burden seems indicated, as these were strong predictors of informal caregivers' well-being during and after treatment.

Background: Current literature is inconsistent in the associations between computed tomography (CT)-based body composition measures and adverse outcomes in older patients with colorectal cancer (CRC). Moreover, the associations with consecutive treatment modalities have not been studied. This study compared the associations of CT-based body composition measures with surgery- and chemotherapy-related complications and survival in older patients with CRC., Materials and Methods: A retrospective single-center cohort study was conducted in patients with CRC aged ≥65 years who underwent elective surgery between 2010 and 2014. Gender-specific standardized scores of preoperative CT-based skeletal muscle (SM), muscle density, intermuscular adipose tissue (IMAT), visceral adipose tissue (VAT), subcutaneous adipose tissue, IMAT percentage, SM/VAT, and body mass index (BMI) were tested for their associations with severe postoperative complications, prolonged length of stay (LOS), readmission, and dose-limiting toxicity using logistic regression and 1-year and long-term survival (range 3.7-6.6 years) using Cox regression. Bonferroni correction was applied to account for multiple testing., Results: The study population consisted of 378 patients with CRC with a median age of 73.4 (interquartile range 69.5-78.4) years. Severe postoperative complications occurred in 13.0%, and 39.4% of patients died during follow-up. Dose-limiting toxicity occurred in 77.4% of patients receiving chemotherapy (n = 53). SM, muscle density, VAT, SM/VAT, and BMI were associated with surgery-related complications, and muscle density, IMAT, IMAT percentage, and SM/VAT were associated with long-term survival. After Bonferroni correction, no CT-based body composition measure was significantly associated with adverse outcomes. Higher BMI was associated with prolonged LOS., Conclusion: The associations between CT-based body composition measures and adverse outcomes of consecutive treatment modalities in older patients with CRC were not consistent or statistically significant., Implications for Practice: Computed tomography (CT)-based body composition, including muscle mass, muscle density, and intermuscular, visceral, and subcutaneous adipose tissue, showed inconsistent and nonsignificant associations with surgery-related complications, dose-limiting toxicity, and overall survival in older adults with colorectal cancer. This study underscores the need to verify whether CT-based body composition measures are worth implementing in clinical practice., (© 2019 The Authors. The Oncologist published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Purpose: Knowledge of caregivers' burden and fatigue before and after patients' treatment for locally advanced head and neck cancer is scarce. Therefore, we aimed to explore caregivers' fatigue and burden in relation to patients' fatigue, distress, and quality of life., Methods: For caregivers, burden and fatigue were assessed. For patients, fatigue severity, distress, and health-related quality of life (HRQoL) were assessed. Measurements were conducted prior to treatment, 1 week, and 3 months after chemoradiotherapy., Results: Caregivers' burden and fatigue followed patients' high peak in distress, fatigue, and diminished HRQoL as a consequence of treatment. Caregivers' baseline fatigue was a predictor for fatigue after chemoradiotherapy. Female spouses with higher baseline levels of fatigue and burden and caring for patients with lower levels of HRQoL seem risk factors for burden after chemoradiotherapy., Conclusions: Attention should be paid to caregivers' burden and fatigue before starting patients' intense treatment with chemoradiotherapy, as both burden and fatigue before starting treatment may contribute to burden and fatigue after chemoradiotherapy.

Background: TKIs are a long-term treatment for GIST, and may have an impact on caregivers., Material and Methods: For this cross-sectional study, patients and caregivers were both included when patients had been treated with TKIs for at least six months. Caregivers completed questionnaires including demographics, distress (Hospital Anxiety and Depression scale), burden (Self-Perceived Pressure from Informal Care) general health (RAND-36), comorbidity (Self-administered Comorbidity Questionnaire), social support (Social Support List - Discrepancies) and marital satisfaction (Maudsley Marital Questionnaire). Patients completed similar questionnaires, without 'burden'. We conducted analyses to explore differences between caregivers with low/moderate versus high levels of burden and low versus high levels of distress., Results: Sixty-one out of seventy-one eligible couples (84%) were included in the analysis. The median age of the caregivers was 60 years; 66% were female and 78% were the patients' spouse. The median age of the patients was 66 years; 43% were female. Caregivers experienced high levels of burden and distress in 10% and 23%, respectively. Caregivers with high levels of burden perceived significantly lower mental health, less vitality, lower general health and high levels of distress. Significantly higher levels of burden were found in non-spouses, caregivers of patients with more treatment-related side-effects, caregivers who spent more hours caring, and those caring for more than one person. For distress, caregivers with high levels of distress perceived significantly more burden, lower social functioning, more role physical and emotional problems, lower mental health, less vitality and lower general health. Furthermore, high levels of distress were found in caregivers of more dependent patients and those caring for more than one person., Conclusions: Caregivers of the patients with GIST treated with TKI are managing well. There is a small, vulnerable group of caregivers with high levels of burden and/or distress, show more health-related problems, both physical and mental, and require adequate support.

Background: In ovarian cancer, cyclooxygenase-2 (COX-2) overexpression is prognostic for poor survival. We investigated the efficacy of celecoxib (C), a selective COX-2 inhibitor, added to docetaxel (Taxotere)/carboplatin (DC) in advanced ovarian cancer., Patients and Methods: In a phase II, randomized study, 400 mg celecoxib b.i.d. was added to first-line DC treatment (DCC). Celecoxib was to be continued after DC termination up to 3 years. Study end points were tolerability, progression-free survival (PFS) and overall survival (OS)., Results: 151 of 196 eligible patients were diagnosed with stage IIIC/IV disease. Median follow-up for patients alive was 32.3 months. Celecoxib was used during a mean of 8.5 months. Twenty-three of 97 DCC patients stopped celecoxib prematurely, mainly due to skin reactions. Complete biochemical response was achieved in 51/78 DC patients (65%) versus 57/78 DCC patients (75%, not significant). In both study arms, median PFS was 14.3 months and median OS 34 months. COX-2 was expressed in 82% of 120 tumor samples retrospectively recovered. The PFS and OS of patients with intermediate/high COX-2 expression were similar to that in the other patients., Conclusion: Celecoxib did not influence PFS and OS, but interpretation of results is hampered by premature celecoxib discontinuation.

Background: We determined to what extent patients with colon cancer stage III ≥ 75 years received adjuvant chemotherapy and the impact on overall and disease-specific survival., Patients and Methods: Data from The Netherlands Cancer Registry on all 8051 patients with colon cancer stage III ≥ 75 years diagnosed in 1997-2009 were included. Trends in adjuvant chemotherapy administration were analysed and multivariable overall and disease-specific survival analyses were performed., Results: The proportion of stage III colon cancer patients ≥ 75 years who received adjuvant chemotherapy increased from 12%in 1997-2000 to 23% in 2007-2009 (P < 0.0001), with a marked age gradient and large geographic variation. Five-year overall survival increased over time from 28% in 1997-2000 to 35% in 2004-2006 (P < 0.0001). Sixty percent of patients died of colorectal cancer. Adjuvant chemotherapy was the strongest positive predictor of survival in this retrospective study (hazard ratio = 0.5; 95% confidence interval: 0.4-0.5)., Conclusion: There has been an increase in administration of adjuvant chemotherapy to elderly patients with stage III colon cancer in The Netherlands since 1997. Survival of elderly patients with stage III colon cancer increased over time, at least partly due to stage migration. The large effect of adjuvant chemotherapy on survival in this study is likely to be associated with the selection of fitter patients for adjuvant treatment.

Background: We investigated treatment of unselected elderly patients with diffuse large B-cell lymphoma (DLBCL) and its subsequent impact on treatment tolerance and survival., Patients and Methods: Data from all 419 advanced-stage DLBCL patients, aged 75 or older and newly diagnosed between 1997 and 2004, were included from five regional population-based cancer registries in The Netherlands. Subsequent data on comorbidity, performance status, treatment, motives for adaptations or refraining from chemotherapy and toxic effects was collected from the medical records. Follow-up was completed until 1st January 2009., Results: Only 46% of patients received the standard therapy [aggressive chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-like chemotherapy]. Motives for withholding chemotherapy were refusal by patient/family, poor performance status or estimated short life expectancy. Of all patients receiving CHOP-like chemotherapy, only 56% could complete at least six cycles. Grade 3 or 4 toxicity occurred in 67% of patients receiving standard therapy. The independent effect of therapy on survival remained after correction for the age-adjusted International Prognostic Index., Conclusions: Standard therapy was applied less often in elderly patients with a subsequent independent negative impact on survival. Furthermore, high toxicity rate and the impossibility of the majority of patients to complete treatment were seen. This implies that better treatment strategies should be devised including a proper selection of senior patients for this aggressive chemotherapy.

Background: Elderly patients with advanced non-small-cell lung cancer (NSCLC) may derive similar benefit from platinum-based chemotherapy as younger patients. Quality of life (QoL) and comprehensive geriatric assessment (CGA) is often advocated to assess benefits and risks., Patients and Methods: A total of 181 chemotherapy-naive patients [≥70 years, performance score (PS) of 0-2] with stage III-IV NSCLC received carboplatin and gemcitabine (CG) (n = 90) or carboplatin and paclitaxel (CP) (n = 91) every 3 weeks for up to four cycles. Primary end point was change in global QoL from baseline compared with week 18. Pretreatment CGA and mini geriatric assessment during and after treatment were undertaken. A principal component (PC) analysis was carried out to determine the underlying dimensions of CGA and QoL and subsequently related to survival., Results: There were no changes in QoL after treatment. The number of QoL responders (CG arm, 12%; CP arm, 5%) was not significantly different. CGA items were only associated with neuropsychiatric toxicity. Quality-adjusted survival was not different between treatment arms. The PC analysis derived from nine CGA, six QoL and one PS score indicated only one dominant dimension. This dimension was strongly prognostic, and physical and role functioning, Groningen Frailty Indicator and Geriatric Depression Scale were its largest contributors., Conclusions: Paclitaxel or gemcitabine added to carboplatin did not have a differential effect on global QoL. CGA was associated with toxic effects in a very limited manner. CGA and QoL items measure one underlying dimension, which is highly prognostic.