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Purpose: As the prognosis for adolescents and young adults (AYAs) with breast cancer has improved, long-term health-related quality of life (HRQoL) has become increasingly important. This study aimed to analyze the long-term HRQoL of AYA breast cancer survivors compared to an age-matched normative population and to identify factors associated with HRQoL., Methods: Secondary analyses were conducted using data from the SURVAYA study. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) was used to assess HRQoL. The Mann-Whitney U test was used to compare HRQoL scores of AYA breast cancer survivors with those of the normative population (n = 409). Linear regression models were constructed to identify patient and treatment characteristics associated with HRQoL., Results: A total of 944 female AYA breast cancer survivors were included, with a median age of 36.0 years and a median follow-up of 12.2 years. AYA breast cancer survivors scored significantly lower on five functional scales: physical, role, emotional, cognitive, and social, and higher on five symptom scales: fatigue, pain, dyspnea, insomnia, and financial impact compared to the normative population. Being in a relationship, having a positive body image, and adaptive coping were positively associated with HRQoL, while older age, chemotherapy, unemployment, and maladaptive coping were negatively associated., Conclusion: AYA breast cancer survivors experience significantly compromised long-term HRQoL compared to an age-matched normative population. These results highlight the need for tailored follow-up care and long-term support, as well as the importance of shared decision-making about the benefits and risks of treatments before initiation., Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interest. Ethical approval: The SURVAYA study was conducted in accordance with the Declaration of Helsinki, approved and reviewed by the Netherlands Cancer Institute Institutional Review Board (IRB-IRBd18122) on 6 February 2019 and registered within clinical trial registration (NCT05379387). The Netherlands Cancer Registry (NCR) provided approval of the linkage, access, and utilization of the clinical data. Informed consent: Informed consent was obtained from all subjects (responders) involved in the study., (© 2025. The Author(s).)

Background: In the field of clinical neuropsychology, researchers and clinicians often use predefined criteria to determine whether there are indications of cognitive impairment. However, corrections and expected false-positive rates are typically available only for uncorrelated tests and simple consensus criteria. Objective: To present an easy-to-use and freely available online tool as a solution for scenarios involving correlated tests and composite consensus criteria, as frequently encountered in clinical neuropsychological research and practice. Method: Our tool employs Monte Carlo simulations to account for the number of participants, thus addressing the uncertainty in estimating false positive rates with small samples. We demonstrate the tool's utility through an example involving cognitive impairment assessment in cancer patients after chemotherapy. Results: The tool reveals considerable uncertainty in false positive rates, especially with small sample sizes, where rates may be higher than traditionally assumed. We found that correlations between tests affect impairment rates differently depending on whether single or multiple test criteria are used. For single-test criteria, lower correlations are associated with more false positives, while for multiple-test criteria, lower correlations lead to fewer false positives. Conclusions: This innovative tool enables more accurate estimation of false positive rates in various neuropsychological conditions. By providing a user-friendly interface and accounting for real-world complexities such as test correlations and composite criteria, our tool empowers clinicians and researchers to: Make informed decisions when interpreting neuropsychological test results.Design more robust research protocols for cognitive impairment studies.Better understand the implications of sample size on false positive rates.

Implementation of patient-reported outcome measures (PROMs) in clinical practice is challenging. We believe effective communication is key to realizing the clinical benefits of PROMs. Communication processes for PROMs in clinical practice typically involve (1) health care professionals (HCPs) inviting patients to complete PROMs, (2) patients completing PROMs, (3) HCPs and patients interpreting the resulting patient-reported outcomes (PROs), and (4) HCPs and patients using PROs for health management. Yet, communication around PROMs remains underexplored. Importantly, patients differ in their skills, knowledge, preferences, and motivations for completing PROMs, as well as in their ability and willingness to interpret and apply PROs in managing their health. Despite this, current communication practices often fail to account for these differences. This paper highlights the importance of personalized communication to make PROMs accessible to diverse populations. Personalizing communication manually is highly labor-intensive, but several digital technologies can offer a feasible solution to accommodate various patients. Despite their potential, these technologies have not yet been applied to PROMs. We explore how existing principles and tools, such as automatic data-to-text generation (including multimodal outputs like text combined with data visualizations) and conversational agents, can enable personalized communication of PROMs in practice., (©Kelly M de Ligt, Saar Hommes, Ruben D Vromans, Eva Boomstra, Lonneke V van de Poll, Emiel J Krahmer. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 05.02.2025.)

Background: Many patients with advanced cancer are unaware of their limited prognosis, however little is known about the change in awareness during the last year of their lives., Aim: To investigate changes in the perception of prognosis in the last year of life of patients with advanced cancer and its associated factors., Design: Prospective, longitudinal, multicentre, observational study in patients with advanced cancer (eQuiPe). Patients completed 3-monthly follow-up questionnaires until death., Setting/participants: Adult patients diagnosed with advanced cancer were recruited by their treating physician or self-enrolled in one of the forty Dutch hospitals. Only deceased patients with available prognostic data were included for analysis ( n  = 801)., Results: Perception of prognosis changes in the last year of life with an increase in the percentage of patients who are aware of their limited prognosis (from 15% to 40%). Especially in the last 6 months of life, most of the changes were towards a more realistic perception of prognosis. Patients who did not want to know their prognosis remained relatively stable in their wish not to know (range: 14%-18%). Time to death was associated with having a perception of prognosis of < 1 year, >1 year or not knowing the prognosis, but was not associated with not wanting to know the prognosis., Conclusion: Becoming aware of their limited prognosis may make patients with advanced cancer more receptive to start end-of-life discussions. Although some patients prefer not to know their prognosis, it remains important to respectfully explore their preferences and wishes for end-of-life care., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Health related quality of life (HRQoL) is increasingly assessed in oncology research and routine care, which has led to the inclusion of HRQoL in prediction models. This review aims to describe the current state of oncological prediction models incorporating HRQoL. A systematic literature search for the inclusion of HRQoL in prediction models in oncology was conducted. Selection criteria were a longitudinal study design and inclusion of HRQoL data in prediction models as predictor, outcome, or both. Risk of bias was assessed using the PROBAST tool and quality of reporting was scored with an adapted TRIPOD reporting guideline. From 4747 abstracts, 98 records were included in this review. High risk of bias was found in 71% of the publications. HRQoL was mainly incorporated as predictor (78% (55% predictor only, 23% both predictor and outcome)), with physical functioning and symptom domains selected most frequently as predictor. Few models (23%) predicted HRQoL domains by other or baseline HRQoL domains. HRQoL was used as outcome in 21% of the publications, with a focus on predicting symptoms. There were no difference between AI-based (16%) and classical methods (84%) in model type selection or model performance when using HRQoL data. This review highlights the role of HRQoL as a tool in predicting disease outcomes. Prediction of and with HRQoL is still in its infancy as most of the models are not fully developed. Current models focus mostly on the physical aspects of HRQoL to predict clinical outcomes, and few utilize AI-based methods., Competing Interests: Declarations. Competing interests: TvdH: None to declare, KdL: None to declare, SvdM: None to declare, NH: None to declare, BH: None to declare, LvdP: None to declare, BdR: None to declare. Ethical approval: No approval needed for this literature review., (© 2024. The Author(s).)

Background: Patients with melanoma receiving immunotherapy with immune-checkpoint inhibitors often experience immune-related adverse events, cancer-related fatigue, and emotional distress, affecting health-related quality of life (HRQoL) and clinical outcome to immunotherapy. eHealth tools can aid patients with cancer in addressing issues, such as adverse events and psychosocial well-being, from various perspectives., Objective: This study aimed to explore the effect of the Cancer Patients Better Life Experience (CAPABLE) system, accessed through a mobile app, on HRQoL compared with a matched historical control group receiving standard care. CAPABLE is an extensively tested eHealth app, including educational material, remote symptom monitoring, and well-being interventions., Methods: This prospective pilot study compared an exploratory cohort that received the CAPABLE smartphone app and a multisensory smartwatch for 6 months (intervention) to a 2:1 individually matched historical prospective control group. HRQoL data were measured with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 at baseline (T0), 3 months (T1), and 6 months (T2) after start of treatment. Mixed effects linear regression models were used to compare HRQoL between the 2 groups over time., Results: From the 59 eligible patients for the CAPABLE intervention, 31 (53%) signed informed consent to participate. Baseline HRQoL was on average 10 points higher in the intervention group compared with controls, although equally matched on baseline and clinical characteristics. When correcting for sex, age, disease stage, and baseline scores, an adjusted difference in fatigue of -5.09 (95% CI -15.20 to 5.02, P=.32) at month 3 was found. No significant nor clinically relevant adjusted differences on other HRQoL domains over time were found. However, information satisfaction was significantly higher in the CAPABLE group (β=8.71, 95% CI 1.54-15.88, P=.02)., Conclusions: The intervention showed a limited effect on HRQoL, although there was a small improvement in fatigue at 3 months, as well as information satisfaction. When aiming at personalized patient and survivorship care, further optimization and prospective investigation of eHealth tools is warranted., (© Itske Fraterman, Lucia Sacchi, Henk Mallo, Valentina Tibollo, Savannah Lucia Catherina Glaser, Stephanie Medlock, Ronald Cornet, Matteo Gabetta, Vitali Hisko, Vadzim Khadakou, Ella Barkan, Laura Del Campo, David Glasspool, Alexandra Kogan, Giordano Lanzola, Roy Leizer, Manuel Ottaviano, Mor Peleg, Konrad Śniatała, Aneta Lisowska, Szymon Wilk, Enea Parimbelli, Silvana Quaglini, Mimma Rizzo, Laura Deborah Locati, Annelies Boekhout, Lonneke V van de Poll-Franse, Sofie Wilgenhof. Originally published in JMIR Cancer (https://cancer.jmir.org).)

Background: The prognosis for patients with several types of cancer has substantially improved following the introduction of immune checkpoint inhibitors, a novel type of immunotherapy. However, patients may experience symptoms both from the cancer itself and from the medication. A prototype of the eHealth tool Cancer Patients Better Life Experience (CAPABLE) was developed to facilitate symptom management, aimed at patients with melanoma and renal cell carcinoma treated with immunotherapy. Better usability of such eHealth tools can lead to improved user well-being and reduced risk of harm. It is unknown for usability evaluations whether certain usability problems would only be evident to patients whose condition closely resembles the target population, or if a broader group of patients would lead to the identification of a broader range of potential usability issues., Objective: This study aims to evaluate the CAPABLE prototype by conducting tests to assess usability, user experience, and perceived acceptability among end users, and to assess any agreements or differences in the results of our wide range of participants., Methods: This usability study was executed by interviewing participants with a melanoma or renal cell carcinoma diagnosis who have received immunotherapy and participants without direct experience with the targeted cancer types who have not received immunotherapy. Participants were asked to review the concept of the tool, perform think-aloud tasks, and complete the System Usability Scale and a Perceived Usefulness questionnaire. Usability problems were extracted from the interview data by independent coding and mapped to an eHealth Usability Problem Framework., Results: We included 21 participants in the study, aged 29 to 73 years; 13 participants who had received immunotherapy and 8 participants who had not received immunotherapy. In total, 76 usability problems were identified. A total of 22 usability problems were in the task-technology fit category of the usability framework, mostly regarding the coaching and symptom functionality of the prototype. Critical problems regarding the symptom monitoring functionality were mainly found by participants who had received immunotherapy. For 8 out of 10 statements in the Perceived Usefulness questionnaire, more than 75% of participants agreed or strongly agreed. The overall mean System Usability Scale score was 80 out of 100 (SD 11.3)., Conclusions: Despite identified usability issues, participants responded positively to the Perceived Usefulness questionnaire regarding the evaluated tool. Further analysis of the usability problems indicates that it was essential to include participants who matched the target end users. Participants treated with immunotherapy, specifically with previous experience in immune-related adverse events, encountered critical problems with symptom reporting that would not have been identified if these participants were not included. For other tasks and functionalities, it seems likely that loosening the inclusion criteria would have resulted in sufficient feedback without critical missing usability issues., (©Savannah Lucia Caterina Glaser, Itske Fraterman, Noah van Brummelen, Valentina Tibollo, Laura Maria Del Campo, Henk Mallo, Sofie Wilgenhof, Szymon Wilk, Vitali Gisko, Vadzim Khadakou, Ronald Cornet, Manuel Ottaviano, Stephanie Medlock. Originally published in JMIR Formative Research (https://formative.jmir.org), 23.01.2025.)

Purpose: To evaluate the cost utility of a 9-month supervised exercise program for patients with metastatic breast cancer (mBC), compared with control (usual care, supplemented with general activity advice and an activity tracker). Evidence on the cost-effectiveness of exercise for patients with mBC is essential for implementation in clinical practice and is currently lacking., Methods: A cost-utility analysis was performed alongside the multinational PREFERABLE-EFFECT randomized controlled trial, conducted in 8 centers across Europe and Australia. Patients with mBC (N = 357) were randomly assigned to either a 9-month, twice-weekly, supervised exercise group (EG) or control group (CG). Costs of the exercise program were calculated through a bottom-up approach. Other health care resource use, productivity losses, and quality of life were collected using country-adapted, self-reported questionnaires. Analyses were conducted from a societal perspective with a time horizon of 9 months. Costs were collected and reported in 2021 Euros (€1 = $1.18 US dollars)., Results: Compared with the CG, EG resulted in a quality-adjusted life-year (QALY) gain of 0.013 (95% CI, -0.02 to 0.05) over a 9-month period. The mean costs of the exercise program were €1,696 per patient with one-on-one supervision (scenario 1) and €609 with one-on-four supervision (scenario 2). These costs were offset by savings in health care and productivity costs, resulting in mean total cost differences of -€163 (scenario 1) and -€1,249 (scenario 2) in favor of EG. The probability of supervised exercise being cost-effective was 65% in scenario 1 and 91% in scenario 2 at a willingness-to-pay threshold of €20,000 per QALY., Conclusion: Exercise for patients with mBC increases quality of life, decreases costs, and is likely to be cost-effective. Group-based supervision is expected to have even higher cost-savings. Our positive findings can inform reimbursement of supervised exercise interventions for patients with mBC.

The response of breast cancer to neoadjuvant chemotherapy (NAC) varies substantially, even when tumours belong to the same molecular or histological subtype 1 . Here we identify the oestrous cycle as an important contributor to this heterogeneity. In three mouse models of breast cancer, we show reduced responses to NAC when treatment is initiated during the dioestrus stage, when compared with initiation during the oestrus stage. Similar findings were observed in retrospective premenopausal cohorts of human patients. Mechanistically, the dioestrus stage exhibits systemic and localized changes, including (1) an increased number of cells undergoing epithelial-to-mesenchymal transition linked to chemoresistance 2-4 and (2) decreased tumour vessel diameter, suggesting potential constraints to drug sensitivity and delivery. In addition, an elevated presence of macrophages, previously associated with chemoresistance induction 5 , characterizes the dioestrus phase. Whereas NAC disrupts the oestrous cycle, this elevated macrophage prevalence persists and depletion of macrophages mitigates the reduced therapy response observed when initiating treatment during dioestrus. Our data collectively demonstrate the oestrous cycle as a crucial infradian rhythm determining chemosensitivity, warranting future clinical studies to exploit optimal treatment initiation timing for enhanced chemotherapy outcomes., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Health-related quality of life (HRQoL) is emerging as an endpoint, adjunct to survival, in cancer treatment. For this reason, the European Organization for Research and Treatment of Cancer (EORTC) has developed standardized quality-of-life questionnaires to collect patient-reported outcome measurement (PROM), which so far have been widely used in clinical trials to evaluate the impact of new drugs on cancer patients. However, while these questionnaires comprehensively describe patient functions, little is known about their association with patient characteristics. This study aims to bridge this gap and investigate the association between patient body composition and HRQoL., Materials and Methods: A retrospective cohort of melanoma patients treated with systemic therapy who completed HRQoL questionnaires and had regular imaging follow-ups was included. The primary endpoint was the association between n = 116 AI-measured longitudinal volumes of thoracic and abdominal organs, subcutaneous and visceral fat, skeleton and muscles (estimated by TotalSegmentator), and physical functioning (PF), role functioning (RF) and fatigue (FA) (estimated by the EORTC-QLQ-C30)., Results: The n = 358 patients were included. Our findings show larger liver, spleen, and gallbladder volumes associated with decreased PF and RF and an increase in FA (p < 0.05). Furthermore, larger muscle volumes were associated with an increase in PF and RF and a decrease in FA (p < 0.01)., Discussion: Our findings show significant associations between AI-measured body and organ analysis and HRQoL in patients with melanoma on systemic treatment. Future research is needed to understand the underlying cause and determine the possible predictive ability of these imaging features., Key Points: Question Are changes in body composition associated with changes in HRQoL in melanoma patients undergoing systemic therapy? Findings AI-based body composition analysis shows that larger muscle volumes are linked to improved HRQoL, while organ enlargement is associated with a decline in it. Clinical relevance Our findings indicate new imaging biomarkers that can help monitor patients and evaluate treatment responses. These biomarkers link patient function to physical changes during treatment, offering insights for creating response evaluation criteria that also consider improvements in quality of life., Competing Interests: Compliance with ethical standards. Guarantor: The scientific guarantor of this publication is Stefano Trebeschi. Conflict of interest: R.G.H.B.-T. is a member of the Scientific Editorial Board for European Radiology (section: oncology). As such they have not participated in the selection nor review processes for this article. The remaining authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. Statistics and biometry: One of the authors has significant statistical expertise. Informed consent: Written informed consent was waived by the Institutional Review Board. Ethical approval: Institutional Review Board approval was obtained. Study subjects or cohorts overlap: None. Methodology: Retrospective Observational Performed at one institution, (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Purpose: We aimed to identify metastatic breast cancer (MBC) patients' preferences for exercise programs and identify patients' characteristics associated with these preferences, to facilitate implementation of exercise programs for MBC patients., Methods: We used data from a multinational cross-sectional survey conducted among MBC patients. Patients reported their preferred exercise frequency, intensity, type, session duration, and supervision mode. We used latent class analysis to identify subgroups with similar preferences and descriptive statistics to compare demographic and clinical characteristics of patients within subgroups., Results: Four distinct classes were identified based on data from 409 participants. Class 1 (47% of participants) is characterized by a preference for moderate exercise with supervision within the health care setting. Most participants in this class had bone metastases. Class 2 (30%) is characterized by a preference for vigorous exercise with supervision. This class included participants who were, on average, younger, and had a higher education level. Class 3 (13%) is characterized by a preference for active walking. These participants were less likely to have bone metastases or comorbidities. Class 4 (10%) is characterized by a preference for recreational walking and included participants who were, on average, older, and less likely to be employed., Conclusion: We identified four classes of patients with different preferences for exercise programs. Many patients with MBC express exercise preferences that meet the current guideline recommendations. Some patients with MBC may benefit from targeted education to align their preferences and behavior with the amount of exercise that is necessary to gain health benefits., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Particularly in genetics, former results can gain new meaning in the course of time. This raises questions about when professionals should recontact patients with new information. The aim of this focus group study is to clarify how different stakeholders in oncology think about the extent and limits of a duty to recontact., Materials and Methods: One focus group with oncology patients (n = 12) and two groups with healthcare professionals (total n = 13) were conducted. In general, there was support for recontacting patients. The scope and extent of this duty was, however, perceived differently. Differences and similarities on the following six contextual factors are discussed: information features, costs and efforts, personal preferences, who is contacted, clinic or research setting, and time., Discussion: Oncology patients were clear in their wish to receive updates while the professionals were more hesitant to consider recontact as a standard of care. This is not surprising as recontacting patients with new information would mean a shift from a patient-initiated approach toward an information-initiated approach. This entails a different way of offering healthcare. Furthermore, the question is not only what professionals' responsibilities are, but how to design a system that complies with patients' wishes to receive updates.

Circulating tumor DNA (ctDNA) detection has multiple promising applications in oncology, but the road toward implementation in clinical practice is unclear. We aimed to support the implementation process by exploring potential future pathways of ctDNA testing. To do so, we studied four ctDNA-testing applications in two cancer types and elicited opinions from 30 ctDNA experts in the Netherlands. Our results showed that the current available evidence differed per application and cancer type. Tumor profiling and monitoring treatment response were found most likely to be implemented in non-small cell lung cancer (NSCLC) within 5 years. For colorectal cancer, applications of ctDNA testing were found to be at an early stage in the implementation process. Demonstrating clinical utility was found a key aspect for successful implementation, but there was no consensus regarding the evidence requirements. The next step toward implementation is to define how clinical utility of biomarkers should be evaluated. Finally, these data indicate that specific challenges for each clinical application and tumor type should be appropriately addressed in a deliberative process involving all stakeholders to ensure implementation of ctDNA testing and timely access for patients., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Purpose: Standardized patient-reported outcomes (PRO) monitoring during and after rectal cancer treatment provides insight into treatment-related toxicities patients experience and improves health-related quality-of-life as well as overall survival. We aimed to select a subset of the PRO version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) for standardized monitoring of treatment-related symptomatic toxicities in rectal cancer., Methods: We used a mixed methods approach including a literature review, and semi-structured interviews with health care providers (HCPs) involved in rectal cancer care and rectal cancer patients. Results from literature and interviews were summarized and used in a modified Delphi procedure to select a PRO-CTCAE subset specific for rectal cancer., Results: Twenty-six PRO-CTCAE symptomatic toxicities were identified from literature. Fifteen HCPs from multiple disciplines (medical, radiation and surgical oncology), and a heterogeneous group of fifteen rectal cancer patients treated with chemotherapy and/or radiotherapy and/or surgery, participated in semi-structured interviews. Ten HCPs (67%) and nine patients (90%) participated in the first Delphi round. The final selected PRO-CTCAE core-subset contained 16 symptomatic toxicities: 'diarrhea', 'fecal incontinence', 'constipation','bloating of the abdomen', 'pain in the abdomen', 'vomiting', 'decreased libido', 'pain during vaginal sex', 'ability to achieve and maintain erection', 'fatigue', 'anxiety', 'feeling that nothing could cheer you up', 'urinary incontinence', 'painful urination', 'general pain', and 'hand-foot syndrome'., Conclusion: Based on a comprehensive mixed methods study, a PRO-CTCAE subset for standardized treatment-related symptomatic toxicity monitoring in rectal cancer was identified. Assessment of the effectiveness and compliance of symptomatic toxicity monitoring using this subset is recommended., (© 2024. The Author(s).)

Purpose: Studies looking into the concordance between late effects reported by physicians vs. those reported by Hodgkin lymphoma (HL) survivors are missing., Methods: A Life Situation Questionnaire focusing on late effects collected data from 1230 HL survivors (median follow-up 14.3 years). Twenty-six disease- and treatment-related late effects from various organ systems were matched with physician-recorded data. The concordance between physicians and survivors was systematically evaluated using percentage agreement and kappa statistics. Potential non-responder biases and associations with patient and disease characteristics were also investigated., Results: Agreement levels (indicated by kappa statistics) varied from none to moderate agreement, with the highest Kappa values observed for myocardial infarction (kappa = 0.55, 95% CI 0.43-0.66) and pulmonary embolism (kappa = 0.55, 95% CI 0.35-0.75). HL survivors consistently reported a higher prevalence of late effects compared with physicians. Notably, the prevalence of subjective symptoms such as persistent fatigue and xerostomia was repeatedly underreported by physicians. A trend towards higher concordance was observed in survivors with higher clinical stage, higher education level, and treatment initiated at younger ages. Additionally, findings indicated that survivors who did not respond to the questionnaire experienced fewer late effects compared to those who did respond., Conclusions: Substantial discrepancies were noted in the reported prevalence of late effects between survivors and physicians, especially for outcomes which are not easily quantified., Implications for Cancer Survivors: It is therefore essential to integrate outcomes reported by both physicians and survivors to achieve a comprehensive assessment of the long-term consequences of HL treatment., (© 2024. The Author(s).)

Purpose: This study aimed to examine the (age-specific) informational needs and support sources used by Adolescent and Young Adult (AYA) cancer survivors throughout their cancer trajectory and socio-demographic and clinical factors associated with most common AYA-related informational needs., Methods: A cross-sectional questionnaire study was conducted among AYA cancer survivors (mean, 10.3 years after diagnosis, SD = 5.6). Informational needs and sources of support were examined via open questions and analyzed via a thematic inductive approach. Responses on informational needs were categorized according to the AYA anamnesis of the Dutch AYA "Young & Cancer" Care Network used in clinical practice. Chi-square and ANOVA tests were performed to assess differences in socio-demographic and clinical characteristics among AYA cancer survivors based on their varying levels of informational needs., Results: In total, 593 AYA cancer survivors were included (mean, 32.2 years at diagnosis, SD = 5.6). Most common informational needs were related to: family and children (23%), fertility and pregnancy (23%), work and reintegration (20%), peers with cancer (13%), and intimacy and sexuality (13%). Females, AYA cancer survivors diagnosed a longer time ago, those with a college/university education, those diagnosed with breast or hematological malignancies, and those treated with chemotherapy were more likely to have AYA-related informational needs. The most often used sources of support were healthcare professionals (76%), family (72%), social life (69%), and websites (47%)., Conclusions: AYA cancer survivors have informational needs related to their life stage including topics like family and children, and fertility. Tailored information services and support are needed, including opportunities to connect with peers and support for relatives. By addressing the informational needs and sources of support for AYA cancer survivors, we can improve AYA care programs and empower AYA cancer survivors to better cope with the consequences associated with their disease., Implications for Cancer Survivors: This study will help to inform the content of AYA websites and platforms and help AYA cancer survivors, relatives, and healthcare professionals to become more aware of the needs of AYA cancer survivors and facilitate better use of relevant information and support services., (© 2024. The Author(s).)

Purpose: This study investigated self-reported clinically relevant cognitive impairment of breast cancer patients in routine clinical care and assessed factors associated with new-onset clinically relevant cognitive impairment., Methods: Cognitive functioning was assessed before start of any treatment (T0) and at 6 (T6) and 12 (T12) months after diagnosis. Cognitive functioning (CF) was measured on a scale of 0-100 with the EORTC QLQ-C30 questionnaire, and the EORTC pre-defined threshold for clinical importance. Multivariable logistic regression analyses was used to identify factors associated with new-onset clinically relevant cognitive impairment at T6 ((CF > 75 at T0 and CF < 75 at T6 and T12) or (CF > 75 at T0 and T6 and <75 at T12))., Results: Pre-treatment, 21% of patients reported clinically relevant cognitive impairment. At T12, percentage was 32%; 20% of patients reported new-onset clinically relevant cognitive impairment at T6 and/or T12. New-onset clinically relevant cognitive impairment was associated with chemo(immuno)therapy and impairment in role and emotional functioning. Younger patients and patients receiving chemo(immuno)therapy were more likely to report new-onset clinically relevant cognitive impairment post treatment., Conclusion: One in five breast cancer patients reported clinically relevant cognitive problems before start of treatment. This percentage further increased within the first year, particularly among patients treated with chemo(immuno)therapy. One in five patients reported new-onset clinically relevant cognitive impairment. Ultimately, these patients may benefit from systematic monitoring and potential referral to interventions., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Patient-reported outcome measures (PROMs) are questionnaires completed by patients to gain insight in their health-related quality of life. However, patients often find the interpretation of PROMS challenging. A personalized narrative, i.e., a story with patients' experiences tailored to the reader, could help explain PROMs and might be appreciated alongside numerical outcomes. We studied how cancer patients perceive PROMs feedback presented in a regular numerical and a novel narrative format., Methods: Cancer patients who completed PROMs in routine clinical practice were recruited. All participants received numerical feedback and a personalized narrative. Semi-structured interviews were conducted to uncover perceptions of both formats. Interviews were analyzed with an inductive reflexive approach to thematic analysis., Results: Twenty-nine patients with breast cancer, melanoma, and bladder cancer participated. Thematic analysis identified six themes: "Understanding: I get the gist of it!"; "Usefulness: Tell me why I should complete PROMs"; "Format preferences: Numbers are cold, narratives are warm"; "Taking action: Can I do something about my score?"; "Personal relevance: Personalized narratives show me what life has in store for me"; and "Personal relevance: That's (not) me!" Numbers seemed to help participants act, whereas narratives may provide emotional support and recognition. Participants identified with the content of the narrative yet differed in how they related to the main character., Conclusion: Personalized narratives could be a useful addition to PROMs feedback. The studied formats seem to serve different purposes; numbers help to facilitate action, personalized narratives provide recognition., Implications for Cancer Survivors: Personalized narratives may be a useful new way to communicate about quality of life to cancer survivors and help them to envision what the impact of cancer can be., (© 2024. The Author(s).)

Background: Evidence on the optimal follow-up schedule after endometrial cancer is lacking. The study aim was to compare satisfaction with care between women who received reduced follow-up care and women who received usual guideline-directed follow-up care for three years after surgery., Methods: The ENSURE (ENdometrial cancer SURvivors' follow-up carE) trial was a non-inferiority randomized controlled multicenter trial in 42 hospitals in the Netherlands. The intervention arm received reduced follow-up care (4 visits/3 years), while the control group received usual follow-up care (8-11 visits/3 years). Primary outcome was overall satisfaction with care, PSQIII score, over three years follow-up, with a non-inferiority margin of 6. Mixed linear regression, intention-to-treat and per-protocol analyses (presented below) were used., Results: Among 316 women included, overall satisfaction with care was not lower in the reduced follow-up (mean 82; SD = 15) compared with the usual follow-up group (mean 80; SD = 15) group (B = 1.80(-2.09;5.68)). At 6, 12 and 36 months, more women (93/94/90%) in the reduced follow-up group were satisfied with their follow-up schedule than in the usual follow-up group (79/79/82%; p < 0.001; p < 0.001; p = 0.050)., Conclusions and Relevance: Women with low-risk, early-stage endometrial cancer who received reduced follow-up care were no less satisfied with their care than women receiving usual follow-up care. Compared with usual follow-up, women in the reduced follow-up group had fewer clinical visits and, at the same time, more often reported being satisfied with their follow-up schedule. Findings suggest that reduced follow-up care may be the new standard, but should be tailored to meet additional needs where indicated., Competing Interests: Declaration of competing interest Authors have no conflict of interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Oncogenic mutations are abundant in the tissues of healthy individuals, but rarely form tumours 1-3 . Yet, the underlying protection mechanisms are largely unknown. To resolve these mechanisms in mouse mammary tissue, we use lineage tracing to map the fate of wild-type and Brca1 -/- ;Trp53 -/- cells, and find that both follow a similar pattern of loss and spread within ducts. Clonal analysis reveals that ducts consist of small repetitive units of self-renewing cells that give rise to short-lived descendants. This offers a first layer of protection as any descendants, including oncogenic mutant cells, are constantly lost, thereby limiting the spread of mutations to a single stem cell-descendant unit. Local tissue remodelling during consecutive oestrous cycles leads to the cooperative and stochastic loss and replacement of self-renewing cells. This process provides a second layer of protection, leading to the elimination of most mutant clones while enabling the minority that by chance survive to expand beyond the stem cell-descendant unit. This leads to fields of mutant cells spanning large parts of the epithelial network, predisposing it for transformation. Eventually, clone expansion becomes restrained by the geometry of the ducts, providing a third layer of protection. Together, these mechanisms act to eliminate most cells that acquire somatic mutations at the expense of driving the accelerated expansion of a minority of cells, which can colonize large areas, leading to field cancerization., (© 2024. The Author(s).)

Objectives: To evaluate an artificial intelligence (AI)-assisted double reading system for detecting clinically relevant missed findings on routinely reported chest radiographs., Methods: A retrospective study was performed in two institutions, a secondary care hospital and tertiary referral oncology centre. Commercially available AI software performed a comparative analysis of chest radiographs and radiologists' authorised reports using a deep learning and natural language processing algorithm, respectively. The AI-detected discrepant findings between images and reports were assessed for clinical relevance by an external radiologist, as part of the commercial service provided by the AI vendor. The selected missed findings were subsequently returned to the institution's radiologist for final review., Results: In total, 25,104 chest radiographs of 21,039 patients (mean age 61.1 years ± 16.2 [SD]; 10,436 men) were included. The AI software detected discrepancies between imaging and reports in 21.1% (5289 of 25,104). After review by the external radiologist, 0.9% (47 of 5289) of cases were deemed to contain clinically relevant missed findings. The institution's radiologists confirmed 35 of 47 missed findings (74.5%) as clinically relevant (0.1% of all cases). Missed findings consisted of lung nodules (71.4%, 25 of 35), pneumothoraces (17.1%, 6 of 35) and consolidations (11.4%, 4 of 35)., Conclusion: The AI-assisted double reading system was able to identify missed findings on chest radiographs after report authorisation. The approach required an external radiologist to review the AI-detected discrepancies. The number of clinically relevant missed findings by radiologists was very low., Clinical Relevance Statement: The AI-assisted double reader workflow was shown to detect diagnostic errors and could be applied as a quality assurance tool. Although clinically relevant missed findings were rare, there is potential impact given the common use of chest radiography., Key Points: • A commercially available double reading system supported by artificial intelligence was evaluated to detect reporting errors in chest radiographs (n=25,104) from two institutions. • Clinically relevant missed findings were found in 0.1% of chest radiographs and consisted of unreported lung nodules, pneumothoraces and consolidations. • Applying AI software as a secondary reader after report authorisation can assist in reducing diagnostic errors without interrupting the radiologist's reading workflow. However, the number of AI-detected discrepancies was considerable and required review by a radiologist to assess their relevance., (© 2024. The Author(s).)

Background: Current patient selection for adjuvant chemotherapy (ACT) after curative surgery for stage II colon cancer (CC) is suboptimal, causing overtreatment of high-risk patients and undertreatment of low-risk patients. Postoperative circulating tumor DNA (ctDNA) could improve patient selection for ACT., Objectives: We conducted an early model-based evaluation of the (cost-)effectiveness of ctDNA-guided selection for ACT in stage II CC in the Netherlands to assess the conditions for cost-effective implementation., Methods: A validated Markov model, simulating 1000 stage II CC patients from diagnosis to death, was supplemented with ctDNA data. Five ACT selection strategies were evaluated: the current guideline (pT4, pMMR), ctDNA-only, and three strategies that combined ctDNA status with pT4 and pMMR status in different ways. For each strategy, the costs, life years, quality-adjusted life years (QALYs), recurrences, and CC deaths were estimated. Sensitivity analyses were performed to assess the impact of the costs of ctDNA testing, strategy adherence, ctDNA as a predictive biomarker, and ctDNA test performance., Results: Model predictions showed that compared to current guidelines, the ctDNA-only strategy was less effective (+2.2% recurrences, -0.016 QALYs), while the combination strategies were more effective (-3.6% recurrences, +0.038 QALYs). The combination strategies were not cost-effective, since the incremental cost-effectiveness ratio was €67,413 per QALY, exceeding the willingness-to-pay threshold of €50,000 per QALY. Sensitivity analyses showed that the combination strategies would be cost-effective if the ctDNA test costs were lower than €1500, or if ctDNA status was predictive of treatment response, or if the ctDNA test performance improved substantially., Conclusion: Adding ctDNA to current high-risk clinicopathological features (pT4 and pMMR) can improve patient selection for ACT and can also potentially be cost-effective. Future studies should investigate the predictive value of post-surgery ctDNA status to accurately evaluate the cost-effectiveness of ctDNA testing for ACT decisions in stage II CC., Competing Interests: S.J.S. received an institutional research grant from Personal Genome Diagnostics (PGDx). G.R.V. reported grants and/or nonfinancial support from BMS, Merck, Servier, Personal Genome Diagnostics, Bayer, Sirtex, Pierre Fabre, Lilly, Delfi Diagnostics, all outside the submitted work, and all financial supports transferred to the institute. J.P. is a founder of Delfi Diagnostics and owns Delfi Diagnostics stock. V.E.V. is a founder of Delfi Diagnostics, serves on the Board of Directors and as an officer for this organization, and owns Delfi Diagnostics stock, which is subject to certain restrictions under university policy. In addition, Johns Hopkins University owns equity in Delfi Diagnostics. V.E.V. divested his equity in Personal Genome Diagnostics (PGDx) to LabCorp in February 2022. V.E.V. is an inventor on patent applications submitted by Johns Hopkins University related to cancer genomic analyses and cell-free DNA for cancer detection that have been licensed to one or more entities, including Delfi Diagnostics, LabCorp, Qiagen, Sysmex, Agios, Genzyme, Esoterix, Ventana, and ManaT Bio. Under the terms of these license agreements, the University and inventors are entitled to fees and royalty distributions. V.E.V. is an advisor to Viron Therapeutics and Epitope. These arrangements have been reviewed and approved by Johns Hopkins University in accordance with its conflict-of-interest policies. D.v.d.B. has provided lectures, expert testimony, and advisory board presence, for Roche Diagnostics, all outside the submitted work and all financial supports transferred to the institute. M.K. reports having an advisory role for Eisai, Nordic Farma, Merck-Serono, Pierre Fabre, and Servier (vergoedingen naar instituut). Institutional scientific grants from Bayer, Bristol Myers Squibb, Merck, Personal Genome Diagnostics (PGDx), Pierre Fabre, Roche, Sirtex, and Servier. PI from the international cohort study PROMETCO with Servier as a sponsor. Non-financial interests: chair of the ESMO RWD-DH working group, co-chair DCCG, PI PLCRC (national observational cohort study), involved in several clinical trials as PI or co-investigator in CRC. G.A.M. is co-founder and board member (CSO) of CRCbioscreen BV, he has a research collaboration with CZ Health Insurances (cash matching to ZonMW grant), he has research collaborations with Exact Sciences, Sysmex, Sentinel Ch. SpA, Personal Genome Diagnostics (PGDx), DELFi, and Hartwig Medical Foundation; these companies provide materials, equipment, and/or sample/genomic analyses, and he has several patents pending/issued. J.M.L.R. is an advisory board and/or speaker at Bayer, BMS, Merck-Serono, Pierre Fabre, Servier, AMGEN, GSK, received research funding paid to the institution from BMS, Pierre Fabre, GSK, Servier, Cleara, HUB organoids B.V., Xilis, and is a board member of the Foundation Hubrecht Organoid Biobank. R.J.A.F. reports grants and nonfinancial support from Personal Genome Diagnostics (PGDx), DELFI Diagnostics, and Cergentis BV; grants from MERCK BV; and nonfinancial support from Pacific Biosciences, outside the submitted work. In addition, R.J.A.F. has several patents pending. V.P.R. received in the past 3 years an unrestricted grant from Intuitive BV, outside of the current work. The remaining authors declare no potential competing interests., (© The Author(s), 2024.)

Chronotype may affect tolerance for circadian disruption induced by shift work. This study examines the association between chronotype, self-reported sleep timing, shift type preference, and sleep problems among nurses, and studies chronotype stability over time. The study included 37,731 Dutch female nurses who completed a baseline (2011) and follow-up questionnaire (2017), with information on shift work (e.g., job history, shift type preference [collected in 2017 only]), and sleep characteristics (e.g., chronotype, preferred sleep-wake time in a work-free period [collected in 2017 only], and sleep problems between working days according to Medical Outcomes Study-Sleep Problem Index II [MOS-SPI-II]). The association between chronotype and sleep timing was examined using (age-adjusted) linear regression. Associations between chronotype and shift type preference and sleep problems (MOS-SPI-II >30) were examined using ordered logistic and Poisson regression, respectively. With later chronotype, midsleep time increased (definite evening vs. intermediate types [reference]: β = 55 min, 95% confidence interval [95% CI]: 54-55), the odds ratio (OR) for 1-point increase in preference for night (2.68; 95% CI: 2.48-2.90) and evening shifts increased (OR 2.20; 95% CI: 2.03-2.38), while the odds for day (OR 0.17; 95% CI: 0.16-0.18) and morning shifts (OR 0.22; 95% CI: 0.21-0.24) decreased. Intermediate chronotype was associated with fewer sleep problems (median MOS-SPI-II = 27.2, p < 0.01), compared with definite morning (28.9) and evening types (31.7). This study shows that chronotype is associated with sleep-wake times in a work-free period, shift type preference, and sleep problems in nurses. Future studies on the association of shift work-induced circadian disruption and health outcomes should therefore consider chronotype as effect-modifier., (© 2024 The Author(s). Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

The European Breast Cancer Council (EBCC) traditionally identifies controversies or major deficiencies in the management of patients with breast cancer and selects a multidisciplinary expert team to collaborate in setting crucial principles and recommendations to improve breast cancer care. The 2024 EBCC manifesto focuses on disparities in the care of patients with metastatic breast cancer. There are several reasons for existing disparities both between and within countries. Our recommendations aim to address the stigma of metastatic disease, which has led to significant disparities in access to innovative care regardless of the gross national income of a country. These recommendations are for different stakeholders to promote the care of patients with metastatic breast cancer across Europe and worldwide., Competing Interests: Declaration of Competing Interest MI reports speaker fees/honoraria from Novartis, Seattle Genetics, Daichi, Menarini/Stemline and Gilead, research grants (to institution) from Pfizer, Roche, Inivata Inc, Natera Inc and Gilead, and meeting/travel grants from Roche, AstraZeneca and Gilead (all outside the submitted work). TS reports personal fees for advisory board participation from MSD and Roche and for invited speaker engagements at regional conferences from Roche and Pfizer (outside the submitted work). EB reports honoraria from Pfizer, Lilly and Incyte, consulting/advisory roles for Pfizer, Sandoz-Novartis, Daiichi Sankyo/AstraZeneca and Menarini, and travel/accommodation/expenses from Pfizer and Novartis. DL reports payment (to institution) from the European Medicines Agency for board participation and payment (to institution) from the ESMO Sarcoma and Rare Cancers meeting for participation as a guest speaker. GSS reports institutional research support from Agendia, AstraZeneca, Merck, Novartis, Roche and Seagen. He is a board member of the Dutch Medicines Evaluation Board. AV-S reports speaker honoraria from Ibex Medical Analytics, Myriad, AstraZeneca, Roche and MSD, advisory board participation for Ibex Medical Analytics and Primaa, travel support from Ibex Medical Analytics and AstraZeneca, research grants from Ibex Medical Analytics, Owkin, Primaa, AstraZeneca and MSD Avenir, and stock options for Ibex Medical Analytics. IM declares small fees as honoraria for advisory boards supported by Eli Lilly, Novartis, Pfizer, SeaGen, Daiichi Sankyo, AstraZeneca, Gilead, and Menarini Stemline. PA reports honoraria from Synthon, Roche and Gilead, consulting or advisory roles for MacroGenics, Boehringer Ingelheim, Novartis, amcure, Roche, Novartis, Amgen, Servier, G1 Therapeutics, Radius Health, Deloitte, Menarini, Gilead Sciences, Incyte and Lilly, research funding from Roche (to institution) and travel/accommodation/expenses from Amgen, MSD Oncology, Roche Belgium, Pfizer, Daiichi Sankyo/AstraZeneca and Gilead Sciences. FC reports consultancy roles for Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, GE Oncology, Genentech, Gilead, GlaxoSmithKline, IQVIA, MacroGenics, Medscape, Merck-Sharp, Merus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre-Fabre, prIME Oncology, Roche, Sanofi, Samsung Bioepis, Seagen, Teva and TouchIME. VPR reports no conflict of interest related to the current article and reports grants from Agendia BV more than 5 years ago. DC reports non-personal relationships (any fees go to employer) with AstraZeneca, Eisai, Seagen, Roche, Pfizer, Lilly, Novartis, Synthon, GSK, Gilead, Daichi and Menarini/Stemline; he is Chair of the Board of the non-profit “Make 2nds Count” charity and the Breast International Group. FP, FVD, OK-P and FL report no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Chemotherapy for various stages of gastroesophageal cancer (GEC) is often neurotoxic. Chemotherapy-induced peripheral neuropathy (CIPN) impairs health-related quality of life (HRQoL). This study investigates the incidence and severity of CIPN and its association with HRQoL in patients with GEC., Patients and Methods: Patients who received chemoradiotherapy or chemotherapy for GEC were identified from the Netherlands Cancer Registry. Patient-reported data (measured using the EORTC QLQ-CIPN20 and EORTC QLQ-C30) were collected through the Prospective Observational Cohort Study of Esophageal-Gastric Cancer Patients (POCOP) at baseline and at 3, 6, 9, 12, 18, and 24 months after treatment initiation. Linear mixed effects models were constructed to assess CIPN and the correlation between CIPN and HRQoL was analyzed using Spearman's correlation., Results: A total of 2,135 patients were included (chemoradiotherapy: 1,593; chemotherapy with curative intent: 295; palliative chemotherapy: 247). In all 3 treatment groups, CIPN significantly increased during treatment (adjusted mean score of CIPN at 6 months: chemoradiotherapy, 8.3 [baseline: 5.5]; chemotherapy with curative intent, 16.0 [baseline: 5.6]; palliative therapy, 25.4 [baseline: 10.7]). For chemoradiotherapy, the adjusted mean score continued to increase after treatment (24 months: 11.2). For chemotherapy with curative intent and palliative therapy, the adjusted mean score of CIPN decreased after treatment but did not return to baseline values. CIPN was negatively correlated with HRQoL in all treatment groups, although significance and strength of the correlation differed over time., Conclusions: Because of the poor prognosis of GEC, it is essential to consider side effects of (neurotoxic) treatment. The high prevalence and association with HRQoL indicate the need for early recognition of CIPN.

Background: The aim of this population-based registry study was to examine the impact of cancer on employment outcomes in adolescent and young adult (AYA) survivors and their partners and associated sociodemographic and clinical characteristics., Methods: A total of 2456 AYA cancer patients, diagnosed in 2013 and aged 18 through 39 years old, were selected from the Netherlands Cancer Registry and linked to employment data from Statistics Netherlands, from which 1252 partners of AYAs could be identified. For both patients and their partners, a control group with same age, migration background, and sex was selected. The impact (i.e., causal effect) was estimated by implementing a doubly robust difference-in-differences method, from 3 years before to 5 years after cancer diagnosis., Results: Patients suffered a reduced employment probability (3.8 percentage points) and number of hours worked when employed (3.8%). This effect was larger for females, and individuals with a migration background, high tumor stage, or diagnosed with a central nervous system tumor/hematologic malignancy. In regard to employment, no significant effect could be found for the patients' partners, although a 5.5 percentage-point increase in employment probability was found in partners who were either unemployed or worked fewer than 400 hours., Conclusions: A cancer diagnosis significantly affects employment outcomes of AYA patients with cancer. Patients at risk should have access to services such as job counseling to help them return into society in the best possible way. No objective impact on partners' employment outcomes was found; however, subjective well-being was not taken into account., Plain Language Summary: This study estimated the causal effect of a cancer diagnosis on employment outcomes. Adolescent and young adult cancer survivors face a reduction in both employment probability and the number of hours worked when employed. Partners that were unemployed or worked the least number of hours a year before diagnosis had a 5.5 percentage-point increased employment probability, but for other partners effects are small., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

The primary objective of the prospective, randomized, multicenter, phase 3 biomarker Microarray Analysis in breast cancer to Taylor Adjuvant Drugs Or Regimens trial (MATADOR: ISRCTN61893718) is to generate a gene expression profile that can predict benefit from either docetaxel, doxorubicin, and cyclophosphamide (TAC) or dose-dense scheduled doxorubicin and cyclophosphamide (ddAC). Patients with a pT1-3, pN0-3 tumor were randomized 1:1 between ddAC and TAC. The primary endpoint was a gene profile-treatment interaction for recurrence-free survival (RFS). We observed 117 RFS events in 664 patients with a median follow-up of 7 years. Hallmark gene set analyses showed significant association between enrichment in immune-related gene expression and favorable outcome after TAC in hormone receptor-negative, human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) (triple-negative breast cancer [TNBC]). We validated this association in TNBC patients treated with TAC on H&E slides; stromal tumor-infiltrating lymphocytes (sTILs) ≥20% was associated with longer RFS (hazard ratio 0.18, p  = 0.01), while in patients treated with ddAC no difference in RFS was seen (hazard ratio 0.92, p  = 0.86, p interaction  = 0.02)., Competing Interests: S.C.L. and H.M.O. received an institutional unrestricted research grant from Sanofi and Amgen to conduct the MATADOR study (ISRCTN61893718); H.M.O. received institutional research support funding from Roche; M.K. received institutional research support funding from Roche, BMS, and AZ; S.C.L. received institutional research support funding from Agendia, Amgen, AstraZeneca, Eurocept, Genentech, Immunomedics (now Gilead), Roche, Sanofi, and TESARO (now GSK). S.C.L. is an advisory board member for AstraZeneca for which the institute receives compensation, and for Cergentis (pro bono). S.C.L. receives funding for educational activities from Daiichi Sankyo, paid to the institute. H.M.O. is an advisory board member for Roche, Pfizer, and Novartis. M.K. is an advisory board member for AZ, BMS, Roche, MSD, and Daiichi for which the institute receives compensation., (© 2024 The Authors.)

Disturbances in the diurnal pattern are associated with several clinical and psychological conditions, including depression and fatigue. Salivary sampling for melatonin, cortisol and cortisone provides a non-invasive method for frequent sampling and obtaining biochemical insight into the diurnal pattern of individuals. Therefore, a new liquid chromatography-tandem mass spectrometry-based method for the measurement of salivary melatonin, cortisol and cortisone was developed and validated. The method required 250 μl saliva, used isotope dilution methodology and was based on a liquid-liquid extraction for sample preparation, reversed-phase chromatography and multiple reaction monitoring on a mass spectrometer for quantitation. The lower limits of quantification obtained were 0.010 nmol/L for melatonin, 0.5 nmol/L for cortisol and 1.00 nmol/L for cortisone and the limits of detection were 0.003 nmol/L, 0.15 nmol/L and 0.1 nmol/L respectively. The method imprecision was ≤14% for all measurands, and the method comparison showed highly comparable results with high correlation coefficients (all ≥0.964). Potential interference of cortisol and cortisone by prednisolone was observed and could be detected by chromatogram review. Typical diurnal patterns for melatonin, cortisol and cortisone were observed in the saliva of 20 cancer survivors who collected saliva throughout the day., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: H. H. van Rossum; Owner and director of Huvaros B.v., Stock ownership and medical director of SelfSafeSure Blood Collection B.V. Has received (indirect) financial support from: Abbott, Beckman, Roche, Siemens, Sysmex, Health Holland and Stichting Treatmeds, M. Lanfermeijer; L.J. van Winden; D.E.J. Starreveld; S. Razab-Sekh; M. van Faassen; E.M.A. Bleiker: Have no known competing financial interest or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The uptake of genetic counseling and predictive genetic testing by family members at risk for hereditary tumor syndromes is generally below 50%. To address this issue, a new guideline was introduced in the Netherlands in 2019 that aims to improve the sharing of information within families. In addition to cascade screening supported by follow-up telephone calls with the proband, municipal records were accessed to allow the geneticist to contact at-risk family members directly. We evaluated this procedure in 32 families with a (likely) pathogenic germline BRCA1/BRCA2 variant diagnosed at our hospital between May 1, 2020, and July 31, 2021, comparing current uptake with outcomes achieved for 33 families diagnosed in 2014. Fifteen months after diagnostic testing of the proband, the uptake was 43% (120/277), comparable to the 44% (87/200) registered previously. Among a subgroup of women at 50% risk aged 25-75 years, 71% (47/66) were tested, comparable to an earlier uptake of 69% (59/86). Of the 34 at-risk relatives we contacted directly, 17 (50%) underwent predictive testing. In conclusion, we found no evidence that the new procedure leads to a substantially increased uptake. Future research should be primarily aimed at understanding intrafamilial communication barriers., (© 2023 National Society of Genetic Counselors.)

Purpose: It is assumed that a segment of breast cancer survivors are cognitively affected after chemotherapy. Our aim is to discover whether there is a qualitatively different cognitively affected subgroup of breast cancer survivors, or whether there are only quantitative differences between survivors in cognitive functioning., Methods: Latent profile analysis was applied to age-corrected neuropsychological data -measuring verbal memory, attention, speed, and executive functioning- from an existing sample of 62 breast cancer survivors treated with chemotherapy. Other clustering methods were applied as sensitivity analyses. Subgroup distinctness was established with posterior mean assignment probability and silhouette width. Simulations were used to calculate subgroup stability, posterior predictive checks to establish absolute fit of the subgrouping model. Subgrouping results were compared to traditional normative comparisons results., Results: Two subgroups were discovered. One had cognitive normal scores, the other -45%- had lower scores. Subgrouping results were consistent across clustering methods. The subgroups showed some overlap; 6% of survivors could fall in either. Subgroups were stable and described the data well. Results of the subgroup clustering model matched those of a traditional normative comparison method requiring small deviations on two cognitive domains., Conclusions: We discovered that almost half of breast cancer survivors after chemotherapy form a cognitively affected subgroup, using a data-driven approach. This proportion is higher than previous studies using prespecified cutoffs observed., Implications for Cancer Survivors: A larger group of cancer survivors may be cognitively affected than previously recognized, and a less strict threshold for cognitive problems may be needed in this population., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: With 5-year survival rates > 85%, gaining insight into the long-term and late health-related conditions of cancer survivors diagnosed in adolescence and young adulthood is of utmost importance to improve their quantity and quality of survival. This study examined the prevalence of and factors associated with, patient-reported health-related conditions and their latency times among long-term adolescent and young adult (AYA) cancer survivors., Methods: AYA cancer survivors (5-20 years after diagnosis) were identified by the population-based Netherlands Cancer Registry (NCR), and invited to participate in the SURVAYA questionnaire study. Participants reported the prevalence and date of diagnosis of health-related conditions. Clinical data were retrieved from the NCR., Results: Three thousand seven hundred seventy-six AYA cancer survivors (response rate 33.4%) were included for analyses. More than half of the AYAs (58.5%) experienced health-related conditions after their cancer diagnosis, of whom 51.4% were diagnosed with two or more conditions. Participants reported conditions related to vision (15.0%), digestive system (15.0%), endocrine system (14.1%), cardiovascular system (11.7%), respiratory system (11.3%), urinary tract system (10.9%), depression (8.6%), hearing (7.4%), arthrosis (6.9%), secondary malignancy (6.4%), speech-, taste and smell (4.5%), and rheumatoid arthritis (2.1%). Time since diagnosis, tumor type, age at diagnosis, and educational level were most frequently associated with a health-related condition., Conclusions: A significant proportion of long-term AYA cancer survivors report having one or more health-related conditions., Implications for Cancer Survivors: Future research should focus on better understanding the underlying mechanisms of, and risk factors for, these health-related conditions to support the development and implementation of risk-stratified survivorship care for AYA cancer survivors to further improve their outcomes., Clinical Trials Registration: NCT05379387., (© 2024. The Author(s).)

Background: Several observational studies have described an inverse association between cancer diagnosis and subsequent dementia risk. Multiple biologic mechanisms and potential biases have been proposed in attempts to explain this association. One proposed explanation is the opposite expression of Pin1 in cancer and dementia, and we use this explanation and potential drug target to illustrate the required assumptions and potential sources of bias for inferring an effect of Pin1 on dementia risk from analyses measuring cancer diagnosis as a proxy for Pin1 expression., Methods: We used data from the Rotterdam Study, a population-based cohort. We estimate the association between cancer diagnosis (as a proxy for Pin1) and subsequent dementia diagnosis using two different proxy methods and with confounding and censoring for death addressed with inverse probability weights. We estimate and compare the complements of a weighted Kaplan-Meier survival estimator at 20 years of follow-up., Results: Out of 3634 participants, 899 (25%) were diagnosed with cancer, of whom 53 (6%) had dementia, and 567 (63%) died. Among those without cancer, 15% (411) were diagnosed with dementia, and 667 (24%) died over follow-up. Depending on the confounding and selection bias control, and the way in which cancer was used as a time-varying proxy exposure, the risk ratio for dementia diagnosis ranged from 0.71 (95% confidence interval [CI] = 0.49, 0.95) to 1.1 (95% CI = 0.79, 1.3)., Conclusion: Being explicit about the underlying mechanism of interest is key to maximizing what we can learn from this cancer-dementia association given available or readily collected data, and to defining, detecting, and preventing potential biases., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: This study aims to (1) explore the prevalence of patient-reported financial difficulties among GIST patients, differentiating between those currently undergoing tyrosine kinase inhibitor (TKI) treatment and those who are not; (2) investigate associations between financial difficulties and sociodemographic and clinical characteristics, work, cancer-related concerns, anxiety and depression and (3) study the impact of financial difficulties on health-related quality of life., Methods: A cross-sectional study was conducted among Dutch GIST patients diagnosed between 2008 and 2018, who were invited to complete a one-time survey between September 2020 and June 2021. Patients completed nine items of the EORTC item bank regarding financial difficulties, seven work-related questions, the Hospital Anxiety and Depression Scale, Cancer Worry Scale and EORTC QLQ-C30., Results: In total, 328 GIST patients participated (response rate 63.0%), of which 110 (33.8%) were on TKI treatment. Patients currently treated with TKIs reported significantly more financial difficulties compared to patients not on TKIs (17.3% vs 8.7%, p = 0.03). The odds of experiencing financial difficulties was 18.9 (95% CI 1.7-214.7, p = 0.02) times higher in patients who were less able to work due to their GIST diagnosis. Patients who experienced financial difficulties had significantly lower global quality of life and functioning, and more frequently reported psychological symptoms as compared to patients who did not report financial difficulties., Conclusion: Even in a country where the costs of TKIs and follow-up care are covered by health insurance, financial difficulties can be present in GIST patients, especially in patients on TKI treatment, and may negatively influence the quality of life., (© 2024. The Author(s).)

Background: Adolescent and young adult cancer survivors (AYAs, aged 18-39 years at first diagnosis) have a higher second cancer risk. Accelerated aging is hypothesized as underlying mechanism and has been described clinically by 6 indicators; fatigue, low quality of sleep, low mood, lack of motivation, subjective memory complaints, and poor exercise tolerance. Using patient-reported outcomes, we aimed to identify clusters of accelerated aging among AYA cancer survivors and to investigate their association with second cancer development., Patients and Methods: Patient, tumor, and treatment data were obtained from the Netherlands Cancer Registry. Patient-reported clinical indicators and second cancer data were obtained from the SURVivors (5-20 years) of cancer in AYAs (SURVAYA) questionnaire study between 1999 and 2015. Latent class and multivariable logistic regression analyses were performed., Results: In total, n = 3734 AYA survivors with known second cancer status (n = 278 [7.4%] second cancers) were included. Four latent clusters were identified and named based on their clinical indicator features; (1) high accelerated aging (31.3%), (2) intermediate accelerated aging without poor exercise tolerance (15.1%), (3) intermediate accelerated aging without lack of motivation (27.4%), and (4) low accelerated aging (26.2%). AYAs in the high accelerated aging cluster were more likely to have second cancer (odds ratio: 1.6; 95% CI, 1.1-2.3) compared to the low accelerated aging cluster., Conclusion: AYAs with a higher burden of accelerated aging were more likely to develop a second cancer. Validation of the clinical indicators and how to best capture them is needed to improve (early) detection of AYAs at high risk of developing second cancer., (© The Author(s) 2023. Published by Oxford University Press.)

Loss of income and out-of-pocket expenditures are important causes of financial hardship in many patients with cancer, even in high-income countries. The far-reaching consequences extend beyond the patients themselves to their relatives, including caregivers and dependents. European research to date has been limited and is hampered by the absence of a coherent theoretical framework and by heterogeneous methods and terminology. To address these shortages, a task force initiated by the Organisation of European Cancer Institutes (OECI) produced 25 recommendations, including a comprehensive definition of socioeconomic impact from the perspective of patients and their relatives, a conceptual framework, and a consistent taxonomy linked to the framework. The OECI task force consensus statement highlights directions for future research with a view towards policy relevance. Beyond descriptive studies into the dimension of the problem, individual severity and predictors of vulnerability should be explored. It is anticipated that the consensus recommendations will facilitate and enhance future research efforts into the socioeconomic impact of cancer and cancer care, providing a crucial reference point for the development and validation of patient-reported outcome instruments aimed at measuring its broader effects., Competing Interests: Declaration of interests WvH reports grants from Koningin Wilhelmina Fonds (KWF), European Cancer League for European Fair Pricing Network (EFPN) project, and OECI; and consulting fees from Raad voor de Rechtspraak. VPR reports grants from KWF, EFPN, OECI, and the National Health Care Institute. JMV reports grants from EFPN. OSL reports support for attending meetings and travel from the Catalan Institute of Oncology (ICO). EA reports a grant from the Norwegian Directorate of Health; and leadership roles on the scientific board of the Norwegian Cancer Association, the advisory board of the Frisch Centre, and the Faculty of Medicine board elected among academic employees. AE reports support for attending meetings and travel from ICO. NF reports support for the present manuscript and for attending meetings from EFPN and OECI; and a budget-based action grant from EU HORIZON. IK reports a leadership role as a patient advocate at the Institute for Gastroenterological Tumors of Croatia (IGET). SS reports a leadership role at Connect Norway. RS is supported by City Cancer Challenge. SV reports a leadership role at IGET. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Patients across Europe face inequity regarding access to anticancer medicines. While access is typically evaluated through reimbursement status or sales data, patients can receive first access through early access programs (EAPs) or off-label use. This study aims to assess the time to patient access at the hospital level, considering different indications and countries. (Pre-)registered access to six innovative medicines (Olaparib, Niraparib, Ipilimumab, Osimeritinib, Nivolumab and Ibritunib) was measured using a cross-sectional survey. First patient access to medicines and indications were collected using the hospital databases. Nineteen hospitals from Hungary, Italy, the Netherlands, Belgium, Switzerland and France participated. Analysis showed that some hospitals achieved patient access before national reimbursement, primarily through EAPs. The average time from EMA-approval to patient access for these medicines was 2.1 years (Range: -0.9-7.1 years). Hospitals in Italy and France had faster access compared to Hungary and Belgium. Variation was also found within countries, with specialized hospitals (x̄: -0.9 years; SD: 2.0) more likely to provide patient access prior to national reimbursement than general hospitals (x̄: 0.4 years; SD: 2.9). Contextual differences were observed, with EAPs or off-label use being more prevalent in Switzerland than Hungary. Recent EMA-approved indications and drug combinations reached patients at a later stage. Substantial variation in patient access time was observed between and within countries. Improving pricing and reimbursement timelines, fostering collaboration between national health authorities and market authorization holders, and implementing nationally harmonized, data-generating EAPs can enhance timely and equitable patient access to innovative cancer treatments in Europe., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Purpose: The accessibility of cancer care faces challenges due to the rising prevalence of colorectal cancer (CRC) coupled with a shrinkage of healthcare professionals-known as the double aging phenomenon. To ensure sustainable and patient-centred care, innovative solutions are needed. This study aims to assess the needs of CRC patients regarding their follow-up care., Methods: This study uses a mixed-method approach divided in three phases. The initial phase involved focus group sessions, followed by semi-structured interviews to identify patients' needs during follow-up. Open analysis was done to define main themes and needs for patients. In the subsequent quantitative phase, a CRC follow-up needs questionnaire was distributed to patients in the follow-up., Results: After two focus groups (n = 14) and interviews (n = 5), this study identified six main themes. Findings underscore the importance of providing assistance in managing both physical and mental challenges associated with cancer. Participants emphasised the need of a designated contact person and an increased focus on addressing psychological distress. Furthermore, patients desire individualised feedback on quality of life questionnaires, and obtaining tailored information. The subsequent questionnaire (n = 96) revealed the priority of different needs, with the highest priority being the need for simplified radiology results. A possible approach to address a part of the diverse needs could be the implementation of a platform; nearly 70% of patients expressed interest in the proposed platform., Conclusions: CRC patients perceive substantial room for improvement of their follow-up care. Findings can help to develop a platform fulfilling the distinct demands of CRC patients during follow-up., (© 2024. The Author(s).)

Background: Support for health-related quality of life (HRQOL) is an essential part of cancer care in the final stages of life, yet empirical guidance regarding HRQOL and symptom trajectories is lacking., Aim: To assess the change in HRQOL and symptom burden in the last year of life in patients with advanced cancer and its association with health care-related factors, cancer-specific treatment, and comorbidity., Methods: A prospective, multicenter, observational study in patients with advanced cancer (eQuiPe). Three monthly questionnaires included European Organization for Research and Treatment of Cancer Quality of Life-C30 and reported continuity of care. Multivariable mixed-effects analysis was used to assess the association between HRQOL and health care-related factors., Results: A total of 762 deceased patients were included with a mean age of 66 (SD, 10) years and 52% were male. The most common primary tumors were lung (29%), colorectal (20%), and breast cancer (13%). Mean overall HRQOL decreased in the last 9 months of life, with the greatest decrease in the last 3 months (β -16.2). Fatigue, pain, appetite loss, dyspnea, constipation, and nausea worsened significantly in the last year of life. Multimorbidity (β -7.5) and a better reported continuity of care (β 0.7) were both significantly associated with the trajectory of HRQOL., Conclusion: Mean overall HRQOL begins to decline 9 months before death, highlighting the need for early identification and (re)assessment of different symptoms as aspects of HRQOL follow different trajectories. Multimorbidity and reported continuity of care may be associated with the trajectory of HRQOL., (© 2023 American Cancer Society.)

Background: Data from microbiomes from multiple niches is often collected, but methods to analyse these often ignore associations between niches. One interesting case is that of the oral microbiome. Its composition is receiving increasing attention due to reports on its associations with general health. While the oral cavity includes different niches, multi-niche microbiome data analysis is conducted using a single niche at a time and, therefore, ignores other niches that could act as confounding variables. Understanding the interaction between niches would assist interpretation of the results, and help improve our understanding of multi-niche microbiomes., Methods: In this study, we used a machine learning technique called latent Dirichlet allocation (LDA) on two microbiome datasets consisting of several niches. LDA was used on both individual niches and all niches simultaneously. On individual niches, LDA was used to decompose each niche into bacterial sub-communities unveiling their taxonomic structure. These sub-communities were then used to assess the relationship between microbial niches using the global test. On all niches simultaneously, LDA allowed us to extract meaningful microbial patterns. Sets of co-occurring operational taxonomic units (OTUs) comprising those patterns were then used to predict the original location of each sample., Results: Our approach showed that the per-niche sub-communities displayed a strong association between supragingival plaque and saliva, as well as between the anterior and posterior tongue. In addition, the LDA-derived microbial signatures were able to predict the original sample niche illustrating the meaningfulness of our sub-communities. For the multi-niche oral microbiome dataset we had an overall accuracy of 76%, and per-niche sensitivity of up to 83%. Finally, for a second multi-niche microbiome dataset from the entire body, microbial niches from the oral cavity displayed stronger associations to each other than with those from other parts of the body, such as niches within the vagina and the skin., Conclusion: Our LDA-based approach produces sets of co-occurring taxa that can describe niche composition. LDA-derived microbial signatures can also be instrumental in summarizing microbiome data, for both descriptions as well as prediction., (© 2024. The Author(s).)

Background: With increasing survival rates of adolescents and young adults (AYAs) with breast cancer, health-related quality of life (HRQoL) becomes more important. An important aspect of HRQoL is sexual QoL. This study examined long-term sexual QoL of AYA breast cancer survivors, compared sexual QoL scores with that of other AYA cancer survivors, and identified factors associated with long-term sexual QoL of AYA breast cancer survivors., Materials and Methods: Data of the SURVAYA study were utilized for secondary analyses. Sexual QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life cancer survivorship core questionnaire (EORTC QLQ-SURV100). Descriptive statistics were used to describe sexual QoL of AYA cancer survivors. Linear regression models were constructed to examine the effect of cancer type on sexual QoL and to identify factors associated with sexual QoL., Results: Of the 4010 AYA cancer survivors, 944 had breast cancer. Mean sexual QoL scores of AYA breast cancer survivors ranged from 34.5 to 60.0 for functional domains and from 25.2 to 41.5 for symptom-orientated domains. AYA breast cancer survivors reported significantly lower sexual QoL compared to AYA survivors of other cancer types on all domains. Age, time since diagnosis, relationship status, educational level, chemotherapy, hormonal therapy, breast surgery, body image, and coping were associated with sexual QoL of AYA breast cancer survivors., Conclusions: AYA breast cancer survivors experience decreased sexual QoL in the long term (5-20 years) after diagnosis and worse score compared to AYA survivors of other cancer types, indicating a clear need to invest in supportive care interventions for those at risk, to enhance sexual well-being., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Testicular cancer incidence among adolescents and young adults (AYAs, aged 18-39 years at diagnosis) is increasing worldwide and most patients will survive the initial disease. Still, detailed epidemiological information about testicular cancer among AYAs is scarce. This study aimed to provide a detailed overview of testicular cancer trends in incidence, treatment, long-term relative survival and mortality by histological subtype among AYAs diagnosed in the Netherlands between 1989 and 2019., Materials and Methods: Data of all malignant testicular cancers (ICD-code C62) were extracted from the Netherlands Cancer Registry. Mortality data were retrieved from Statistics Netherlands. European age-standardized incidence and mortality rates with average annual percentage change statistics and relative survival estimates up to 20 years of follow-up were calculated., Results: A total of 12 528 testicular cancers were diagnosed between 1989 and 2019. Comparing 1989-1999 to 2010-2019, the incidence increased from 4.4 to 11.4 for seminomas and from 5.7 to 11.1 per 100 000 person-years for non-seminomas. Rising trends were most prominent for localized disease. Radiotherapy use in localized testicular seminomas declined from 78% in 1989-1993 to 5% in 2015-2019. Meanwhile, there was a slight increase in chemotherapy use. Most AYAs with localized seminomas and non-seminomas received active surveillance only (>80%). Overall, relative survival estimates remained well above 90% even at 20 years of follow-up for both seminomas and non-seminomas. Mortality rates declined from 0.5 to 0.4 per 100 000 person-years between 1989-1999 and 2010-2019., Conclusions: The incidence of seminoma and non-seminoma testicular cancers significantly increased in AYAs in the Netherlands between 1989 and 2019. There was a shift towards less-aggressive treatment regimens without negative survival effects. Relative survival estimates remained well above 90% at 20 years of follow-up in most cases. Testicular cancer mortality was already low, but has improved further over time, which makes survivorship care an important issue for these young adults., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: For adolescent and young adult (AYA) cancer survivors with a good prognosis, having a healthy lifestyle prevents morbidity and mortality after treatment. The aim of this study was to investigate the prevalence of (un)healthy lifestyle behaviors and related determinants in AYA cancer survivors., Methods: A population-based, cross-sectional study was performed among long-term (5-20 years) AYA cancer survivors (18-39 years old at diagnosis) registered within the Netherlands Cancer Registry. Self-reported questionnaires data about health behaviors were used to calculate the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) adherence score. Associations between the score and clinical/sociodemographic determinants of (un)healthy behaviors were investigated using logistic regression models., Results: The mean WCRF/AICR score was low to moderate, 3.8 ± 1.2 (0.5-7.0) (n = 3668). Sixty-one percent adhered to "limit the consumption of sugar sweetened drinks," 28% to "be a healthy weight," 25% to "fruit and vegetable consumption," and 31% to "limit alcohol consumption." Moderate and high adherence were associated with being a woman (OR moderate  = 1.46, 95% CI = 1.14-1.85, and OR high  = 1.87, 95% CI = 1.46-2.4) and highly educated (OR moderate  = 1.54, 95% CI = 1.30-1.83, and OR high  = 1.87, 95% CI = 1.46-2.4). Low adherence was associated with smoking (OR moderate  = 0.68, 95% CI = 0.50-0.92, and OR high  = 0.30, 95% CI = 0.21-0.44) and diagnosis of germ cell tumor (OR moderate  = 0.58, 95% CI = 0.39-0.86, and OR high  = 0.45, 95% CI = 0.30-0.69)., Conclusions: Adherence to the 2018 WCRF/AICR lifestyle recommendations was low to moderate, especially regarding body weight, fruit, vegetables, and alcohol consumption. Men, current smokers, lower-educated participants, and/or those diagnosed with germ cell tumors were less likely to have a healthy lifestyle., Implications for Cancer Survivors: Health-promotion programs (e.g., age-specific tools) are needed, focusing on high-risk groups., (© 2024. The Author(s).)

Purpose: Adolescent and young adult cancer survivors (AYAs) are at increased risk of long-term and late effects, and experience unmet needs, impacting their health-related quality of life (HRQoL). In order to provide and optimize supportive care and targeted interventions for this unique population, it is important to study HRQoL factors' interconnectedness on a population level. Therefore, this network analysis was performed with the aim to explore the interconnectedness between HRQoL factors, in the analysis described as nodes, among long-term AYAs., Methods: This population-based cohort study used cross-sectional survey data of long-term AYAs, who were identified by the Netherlands Cancer Registry (NCR). Participants completed a one-time survey (SURVAYA study), including the EORTC survivorship questionnaire (QLQ-SURV111) to assess their long-term HRQoL outcomes and sociodemographic characteristics. The NCR provided the clinical data. Descriptive statistics and a network analysis, including network clustering, were performed., Results: In total, 3596 AYAs (on average 12.4 years post diagnosis) were included in our network analysis. The network was proven stable and reliable and, in total, four clusters were identified, including a worriment, daily functioning, psychological, and sexual cluster. Negative health outlook, part of the worriment cluster, was the node with the highest strength and its partial correlation with health distress was significantly different from all other partial correlations., Conclusion: This study shows the results of a stable and reliable network analysis based on HRQoL data of long-term AYAs, and identified nodes, correlations, and clusters that could be intervened on to improve the HRQoL outcomes of AYAs., (© 2024. The Author(s).)

Background: Cognitive problems contribute to decline in work performance. We evaluated (1) the effectiveness of basic self-management and extensive therapist-guided online cognitive rehabilitation on attainment of individually predetermined work-related goals among occupationally active cancer survivors, and (2) whether effectiveness of the programs differed for survivors with and without formal cognitive impairment., Methods: In a 3-arm randomized controlled trial (NCT03900806), 279 non-central nervous system cancer survivors with cognitive complaints were assigned to the basic program (n = 93), the extensive program (n = 93), or a waiting-list control group (n = 93). Participants completed measurements pre-randomization (T0), 12 weeks post-randomization upon program completion (T1), and 26 weeks post-randomization (T2). Mixed-effects modeling was used to compare intervention groups with the control group on goal attainment, and on self-perceived cognitive problems, work ability, and health-related quality of life., Results: Participants in the extensive program achieved their predetermined goals better than those in the control group, at short- and long-term follow-up (effect size [ES] = .49; P < .001; ES = .34; P = .014). They also had fewer recovery needs after work (ES = -.21; P = .011), more vitality (ES = .20; P = .018), and better physical role functioning (ES = .0.43 P = .015) than controls. At long-term follow-up, this finding persisted for physical role functioning (ES = .42; P = .034). The basic program elicited a small positive nonsignificant short-term (not long-term) effect on goal attainment for those with adequate adherence (ES = .28, P = .053). Effectiveness of the programs did not differ for patients with or without cognitive impairment., Conclusions: Internet-based therapist-guided extensive cognitive rehabilitation improves work-related goal attainment. Considering the prevalence of cognitive problems in survivors, it is desirable to implement this program., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Few studies have comprehensively investigated the long-term second cancer risk among adolescent and young adult (AYA, aged 15-39 years) cancer survivors. This study investigated the long-term second cancer risk by including the full range of first and second cancer combinations with at least 10 observations in the Netherlands between 1989 and 2018., Materials and Methods: First and second primary cancer data of all 6-month AYA cancer survivors were obtained from the nationwide population-based Netherlands Cancer Registry. Excess cancer risk compared to the general population was assessed with standardized incidence ratio (SIR) and absolute excess risk (AER) statistics up to 25 years after diagnosis. Cumulative incidences were estimated, using death as a competing risk factor. Analyses were carried out with and without applying multiple cancer rules., Results: The cohort included 99 502 AYA cancer survivors. Male survivors had a 2-fold higher risk of developing any cancer compared to the general population, whereas this was around 1.3-fold in females. AERs were 17.5 and 10.1 per 10 000 person-years for males and females. The long-term excess risk of cancer was significantly higher for most first and second primary cancer combinations, but comparable and lower risk estimates were also observed. Application of the multiple cancer rules resulted in a noticeable risk underestimation in melanoma, testicular, and breast cancer survivors. Risk outcomes remained similar in most cases otherwise. The cumulative incidence of second cancer overall increased over time up to 8.9% in males and 10.3% in females at 25 years' follow-up. Highest long-term cumulative incidences were observed among lymphoma survivors (13.3% males and 18.9% females)., Conclusions: AYA cancer survivors have a higher cancer risk compared to the general population for most cancers up to 25 years after their initial cancer diagnosis. Additional studies that investigate risk factors for the specific cancer type combinations are needed to develop personalized follow-up strategies., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)