Fehlende Werte bei Patienten-berichteten Endpunkten in einer Längsschnittstudie bei fortgeschrittenem und metastasiertem Krebs

Missing patient-reported outcomes (PROs) are common in follow-up visits for longitudi-nal studies. However, the rates of missing values are relatively high in relation to health deterioration and premature death in patients with advanced stages of cancer. This study aims to investigate the rates and patterns of missing PROs data as well as to ex-plore the association between patient characteristics and time-to-dropout or time-to-death for a better understanding of how the missing data mechanism could be applied to missing PROs data in severely affected patients. This is an exploratory study using data from the Oncological Social Care Project. Missing rates and missing data patterns were reported using cumulative numbers and rates. The competing-risk analysis, using Fine and Gray’s proportional sub-distribution hazards model, was performed to explore factors associated with time-to-dropout when considering death as a competing event. Additionally, a Cox regression model was used to explore factors associated with time-to-death. A total of 362 patients were observed. The cumulative missing rate for assessing PROs was around 28% and 19%, caused by premature death and dropout, respectively. Being divorced or widowed (SHR=2.71; 95%CI: 1.12–6.56) and having poor social support (SHR=2.10; 95%CI: 1.01–4.35) were associated with early dropout. The presence of malignant neoplasm of pancreas cancer (HR = 2.48; 95%CI: 1.27–4.85) and a medium level of education (HR = 1.58; 95%CI: 1.02–2.45) were associated with premature death. Dropping out early from the study was associated with low baseline global health status/quality of life (GH/QoL) (SHR=1.14; 95%CI: 1.01–1.27) and low baseline role functioning, such as limited ability to do work or daily activities (SHR=1.10; 95%CI: 1.01–1.19). Furthermore, worsening scores of GH/QoL, functioning, and symptoms at baseline and at the last visit were associated with premature death. In the advanced stages of cancer research, high rates of missing PROs data should be expected. The worsening of health-related quality of life (e.g., GH/QoL, physical functioning, fatigue scores) was associated with missing PROs data, suggesting that the missing data is not completely random. The investigation of patient characteristics as-sociated with missing data is also informative and a prerequisite for further proper analysis of the data.Fehlende von den Patienten berichteten Ergebnisse (patient-reported outcomes: PROs) sind bei Nachuntersuchungen im Rahmen von Langzeitstudien üblich. Die Raten fehlender Werte sind jedoch relativ hoch, wenn es um die Verschlechterung des Gesundheitszustands und den vorzeitigen Tod von Patienten in fortgeschrittenen Krebsstadien geht. Ziel dieser Studie ist es, die Raten und Muster fehlender PRO-Daten zu untersuchen sowie den Zusammenhang zwischen Patientenmerkmalen und der Zeit bis zum Abbruch bzw. bis zum Tod zu erforschen, um besser zu verstehen, wie der Mechanismus fehlender Daten auf fehlende PRO-Daten bei schwer betroffenen Patienten angewendet werden könnte. Es handelt sich um eine explorative Studie, die Daten aus dem Oncological Social Care Project verwendet. Fehlende Raten und Muster fehlender Daten wurden anhand kumulativer Zahlen und Raten angegeben. Eine Analyse des konkurrierenden Risikos unter Verwendung des proportionalen Unterverteilungs-Hazards-Modells von Fine und Gray wurde durchgeführt, um Faktoren zu untersuchen, die mit der Zeit bis zum Abbruch in Verbindung stehen, wenn der Tod als konkurrierendes Risiko betrachtet wird. Zusätzlich wurde ein Cox-Regressionsmodell verwendet, um Faktoren zu untersuchen, die mit der Zeit bis zum Tod in Verbindung stehen. Insgesamt wurden 362 Patienten beobachtet. Die kumulative Missingrate für die Bewertung der PROs lag bei 28% bzw. 19%, verursacht durch vorzeitigen Tod bzw. Drop-out. Geschieden oder verwitwet zu sein (SHR=2,71; 95%KI: 1,12 – 6,56) und geringe soziale Unterstützung (SHR=2,10; 95%KI: 1,01 – 4,35) waren mit einem frühen Abbruch verbunden. Das Vorhandensein einer bösartigen Neubildung der Pankreas (HR=2,48; 95%KI: 1,27 - 4,85) und ein mittleres Bildungsniveau (HR=1,58; 95%KI: 1,02 - 2,45) waren mit einem vorzeitigen Tod assoziiert. Ein vorzeitiger Abbruch aus der Studie war mit einem niedrigen Ausgangswert für den globalen Gesundheitszustand/die Lebensqualität (GH/QoL) (SHR=1,14; 95%KI: 1,01 - 1,27) und einem niedrigen Ausgangswert für die Rollenfunktion, wie z. B. einer eingeschränkten Fähigkeit zur Ausübung von Arbeit oder täglichen Aktivitäten (SHR=1.10; 95%KI: 1,01 - 1,19) assoziiert. Darüber hinaus war eine Verschlechterung der Werte für GH/QoL, Funktionsfähigkeit und Symptome zu Studienbeginn und bei der letzten Visite mit einem vorzeitigen Versterben assoziiert. In den fortgeschrittenen Stadien der Krebsforschung sind hohe Raten an fehlenden PRO-Daten zu erwarten. Die Verschlechterung der gesundheitsbezogenen Lebensqualität (z. B. GH/QoL, körperlichen Funktionsfähigkeit, Müdigkeit) stand in Verbindung mit fehlenden PROs-Daten. Das bedeutet, dass der Mechanismus der fehlenden Daten nicht völlig zufällig ist. Die Untersuchung von Patientenmerkmalen, die mit fehlenden Daten in Verbindung stehen, ist aufschlussreich und eine Voraussetzung für die weitere korrekte Auswertung der Daten

Characteristics and patient-reported outcomes associated with dropout in severely affected oncological patients: an exploratory study

Background: Patient-reported outcome measures (PROMs) are commonly-used surrogates for clinical outcomes in cancer research. When researching severe diseases such as cancer, it is difficult to avoid the problem of incomplete questionnaires from drop-outs or missing data from patients who pass away during the observation period. The aim of this exploratory study was to explore patient characteristics and the patient-reported outcomes associated with the time-to-dropout. Methods: In an Oncological Social Care Project (OSCAR) study, the condition of the participants was assessed four times within 12 months (t0: baseline, t1: 3 months, t2: 6 months, and t3: 12 months) by validated PROMs. We performed competing-risk regressions based on Fine and Gray's proportional sub-distribution hazards model for exploring factors associated with time-to-dropout. Death was considered a competing risk. Results: Three hundred sixty-two participants were analyzed in the study. 193 (53.3%) completed a follow-up after 12 months, 67 (18.5%) patients dropped out, and 102 patients (28.2%) died during the study period. Poor subjective social support was related to a higher risk of drop-out (SHR = 2.10; 95%CI: 1.01-4.35). Lower values in health-related quality of life were related to drop-out and death. The sub-scales global health status/QoL, role functioning, physical functioning, and fatigue symptom in the EORTC QLQ-C30 were key characteristics of early drop-out. Conclusion: Severely affected cancer patients with poor social support and poor quality of life seem more likely to drop out of studies than patients with higher levels of social support and a better quality of life. This should be considered when planning studies to assess advanced cancer patients. Methods of close continued monitoring should be actively used when patient experiences a substantial deterioration in their health-related quality of life and symptoms during the study. Results for such studies have to be interpreted with caution in light of specific drop-out mechanisms

Head and neck cancer patients with geriatric deficits are more often non-responders and lost from follow-up in quality of life studies

OBJECTIVES: To identify associations between frailty and non-response to follow-up questionnaires, in a longitudinal head and neck cancer (HNC) study with patient-reported outcome measures (PROMs).MATERIALS AND METHODS: Patients referred with HNC were included in OncoLifeS, a prospective data-biobank, underwent Geriatric Assessment (GA) and frailty screening ahead of treatment, and were followed up at 3, 6, 12 and 24 months after treatment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Head and Neck 35. Statistical analysis for factors associated with non-response was done using Generalized Linear Mixed Models.RESULTS: 289 patients were eligible for analysis. Mean age was 68.4 years and 68.5% were male. Restrictions in Activities of Daily Living [OR 4.46 (2.04-9.78)] and Instrumental Activities of Daily Living [OR 4.33 (2.27-8.24)], impaired mobility on Timed Up and Go test [OR 3.95 (1.85-8.45)], cognitive decline [OR 4.85 (2.28-10.35)] and assisted living (OR 5.54 (2.63-11.67)] were significantly associated with non-response. Frailty screening, with Geriatric 8 and Groningen Frailty Indicator, was also associated with non-response [OR, respectively, 2.64 (1.51-4.59) and 2.52 (1.44-4.44)]. All findings remained significant when adjusted for other factors that were significantly associated with non-response, such as higher age, longer study duration and subsequent death.CONCLUSION: Frail HNC patients respond significantly worse to follow-up PROMs. The drop-out and underrepresentation of frail patients in studies may lead to attrition bias, and as a result underestimating the effect sizes of associations. This is of importance when handling and interpreting such data.</p

Hygienic maintenance in patients with maxillae atrophy and in oncological patients with maxillary resection rehabilitated with zygomatic implants: A nested monocentric prospective cohort study

Objective: To assess peri-implant soft tissues condition, comparing clinical parameters of implants placed in patients with atrophic upper jaws and patients who underwent maxillary resection for oncological reasons.Background: Zygomatic implants (ZIs) in oncologic patients could be affected by more complications compared to implants placed in atrophic maxillae. The soft tissue condition is an essential requirement for implant success, but few studies have investigated this topic.Methods: A nested monocentric prospective parallel cohort (atrophic vs. oncological patients) study was performed. Clinical visits and professional hygiene sessions were performed every three months, and bleeding on probing (BOP), probing pocket depth (PPD), gingival index (GI), plaque index (PI) and implant mobility were recorded by a blind outcome assessor.Results: In total, 77 ZIs placed in 21 patients were evaluated: 54 (70.1%) ZIs were inserted in patients belonging to the atrophic cohort (PAM) and 23 (29.9%) ZIs in the oncologic cohort (OP). The probability of having BOP at the considered mean follow-up (27 months) was 24.8% (95% CI 19.0-31.9) for PAM and 22.9% (95% CI 15.1-33.9) OP. The mean PPD values were 2.78 +/- 1.28 (range 1-8) in PAM and 2.91 +/- 1.98 (range 0-10) in OP. None of the implants showed mobility. No associations between group belongingness and the entity of PPD, PI, GI and the risk of BOP were found, adjusting for the considered confounding factors (age, smoking and implant position).Conclusions: Under a strict supportive hygiene therapy protocol ZIs in oncologic patients showed similar peri-implant tissue conditions to that of patients with maxillary atrophy

On frailty, geriatric assessment and clinical outcomes in patients with head and neck cancer

The incidence of cancer, including head and neck cancer, has significantly increased over the past decades, largely due to the aging population. Head and neck cancer, typically squamous cell carcinomas of the oral cavity, pharynx, and larynx, is showing rising incidence across all age groups. Curative treatment ranges from surgery to (chemo)radiotherapy and is often multimodal. Decision-making often considers chronological age rather than biological age. Increased vulnerability, or frailty, is often poorly recognized by oncologists. This work reveals that frailty is more common among patients with head and neck cancer compared to those with other solid tumors, as well as greater cognitive issues, poorer mobility, and a lower quality of life. In patients with complex skin malignancies in the head and neck region, frailty, prolonged surgery duration, and the use of general anesthesia are associated with increased postoperative complications. Although frailty is strongly linked to postoperative complications after head and neck cancer surgery, it is not associated with increased radiotoxicity during and after treatment. Patients identified as frail experience a decline in quality of life and functioning both in the short and long term. In a geriatric assessment, abnormalities across all domains are related to a decline in quality of life, but the cumulative number of deficient domains is most strongly associated with poorer quality of life. Vulnerable patients exhibit poorer response to quality of life questionnaires, which may increase the risk of bias in studies investigating frail patients and lead to an underestimation of actual differences

The Effect of Collaborative Reviews of Electronic Patient-Reported Outcomes on the Congruence of Patient- and Clinician-Reported Toxicity in Cancer Patients Receiving Systemic Therapy: Prospective, Multicenter, Observational Clinical Trial

Background Electronic patient-reported outcomes (ePRO) are a relatively novel form of data and have the potential to improve clinical practice for cancer patients. In this prospective, multicenter, observational clinical trial, efforts were made to demonstrate the reliability of patient-reported symptoms. Objective: The primary objective of this study was to assess the level of agreement κ between symptom ratings by physicians and patients via a shared review process in order to determine the future reliability and utility of self-reported electronic symptom monitoring. Methods Patients receiving systemic therapy in a (neo-)adjuvant or noncurative intention setting captured ePRO for 52 symptoms over an observational period of 90 days. At 3-week intervals, randomly selected symptoms were reviewed between the patient and physician for congruency on severity of the grading of adverse events according to the Common Terminology Criteria of Adverse Events (CTCAE). The patient-physician agreement for the symptom review was assessed via Cohen kappa (κ), through which the interrater reliability was calculated. Chi-square tests were used to determine whether the patient-reported outcome was different among symptoms, types of cancer, demographics, and physicians’ experience. Results Among the 181 patients (158 women and 23 men; median age 54.4 years), there was a fair scoring agreement (κ=0.24; 95% CI 0.16-0.33) for symptoms that were entered 2 to 4 weeks before the intended review (first rating) and a moderate agreement (κ=0.41; 95% CI 0.34-0.48) 4 for symptoms that were entered within 1 week of the intended review (second rating). However, the level of agreement increased from moderate (first rating, κ=0.43) to substantial (second rating, κ=0.68) for common symptoms of pain, fever, diarrhea, obstipation, nausea, vomiting, and stomatitis. Similar congruency levels of ratings were found for the most frequently entered symptoms (first rating: κ=0.42; second rating: κ=0.65). The symptom with the lowest agreement was hair loss (κ=–0.05). With regard to the latency of symptom entry into the review, hardly any difference was demonstrated between symptoms that were entered from days 1 to 3 and from days 4 to 7 before the intended review (κ=0.40 vs κ=0.39, respectively). In contrast, for symptoms that were entered 15 to 21 days before the intended review, no congruency was demonstrated (κ=–0.15). Congruency levels seemed to be unrelated to the type of cancer, demographics, and physicians’ review experience. Conclusions The shared monitoring and review of symptoms between patients and clinicians has the potential to improve the understanding of patient self-reporting. Our data indicate that the integration of ePRO into oncological clinical research and continuous clinical practice provides reliable information for self-empowerment and the timely intervention of symptoms

Enhancing adjustment to parental cancer: counselling interventions for families with a parent with cancer

The challenges of a parental cancer diagnosis not only affect the patients themselves, but the entire family. Moreover, there is evidence that family members are at increased risk of developing psychosocial problems. Therefore, the aim of the research projects presented within this cumulative dissertation was to obtain a better insight of the impact of parental cancer on the family and to develop, implement and evaluate interventions to support families in this exceptional situation. The first two publications cover results of the feasibility of and the lessons learned from a web-based intervention program during the first months of treatment. Furthermore, it reports on psychological adjustment in children of a parent with cancer, family satisfaction and communication, and on the effect of minimal contact interventions on the couple. Due to the low enrolment rate, feasibility of the web-based program was limited. Baseline data of the 28 participating children showed a good adjustment to the parental cancer diagnosis and high family communication levels. Couples showed signs of anxiety and decreased optimism scores at baseline, which slightly improved in patients. Feedback from participating families exhibit that the program was helpful for families with a newly diagnosed parent who are in need of specific information on cancer and family. The third publication discusses the feasibility and acceptability of a face-to-face short-term counselling intervention. Data showed a limited feasibility but good acceptability of the counselling. It was considered recommendable and helpful by nearly all participating families. The enrolment rate was low due to different reasons, such as having no need, lack of time, or local distance. Our research projects suggest that a parental cancer diagnosis may represent a burden, may trigger anxiety and may decrease optimism. Low-threshold interventions represent a helpful option to use at a time when needed

Using the patient perspective to personalize psycho-oncological care for chronic cancer-related fatigue

Ongeveer een kwart van alle mensen met kanker ervaart chronische kanker-gerelateerde vermoeidheid (CKV) nadat de behandeling voor kanker is afgerond. Patiënten met CKV worden beperkt in hun dagelijkse activiteiten. Eerder onderzoek naar CKV richtte zich vooral op vrouwen met borstkanker tijdens de behandeling voor kanker en niet-helpende factoren van CKV. Ook werd in grote groepen onderzoek gedaan naar effectiviteit van psychosociale behandelingen voor CKV. Er is echter nog onvoldoende bekend over welke behandeling het beste werkt voor wie.Om dit te onderzoeken, werd in dit proefschrift onderzoek uitgevoerd bij het Helen Dowling Instituut naar ervaringen van het individu met CKV. Als eerste werd een overkoepelend overzicht gemaakt van zestien studies naar ervaringen en omgaan met CKV. Hieruit kwam naar voren dat het lichaam centraal staat in hoe patiënten CKV ervaren en ermee omgaan. Ook werden interviews afgenomen bij een diverse groep van 25 mensen met ernstige CKV om meer inzicht te krijgen in hoe CKV in het lichaam ervaren wordt. Deze mensen hadden verschillende vormen van kanker en kregen hiervoor verschillende behandelingen. De onzichtbaarheid van CKV en het chronisch vermoeide lichaam stonden vaak op een negatieve manier op de voorgrond, waardoor dagelijkse en sociale activiteiten niet langer mogelijk waren om te kunnen doen. Verder werd tijdens de interviews ook gevraagd naar wat kan helpen bij het omgaan met CKV, waarbij het vormen van nieuwe helpende gewoontes en acceptatie van CKV belangrijk bleek. De netwerkbenadering kijkt naar relaties tussen verschillende relevante factoren. Hierdoor is het mogelijk om met intensieve longitudinale dataverzameling binnen het individu te onderzoeken hoe het netwerk van factoren en CKV eruitziet voor die persoon. Door met behulp van netwerkanalyses te kijken naar het individuele netwerk, wordt inzicht verkregen in wat voor die persoon helpende en minder helpende factoren zijn en kan de behandeling daarop afgestemd worden. In een proof-of-concept studie werd deze netwerkbenadering toegepast en alle ervaringskennis, therapeutische ervaring en eerder onderzoek naar groepen patiënten met CKV samengebracht. Er werden 24 vragen over symptomen, emoties, helpende en niet-helpende manieren van omgaan met CKV en context geprogrammeerd als ‘Ecological Momentary Assessment’ (EMA)-app Energie InZicht. Vijf patiënten met als hoofdprobleem CKV op de wachtlijst voor psycho-oncologische zorg bij het Helen Dowling Instituut kregen vijf keer per dag gedurende drie weken op hun mobiele telefoon deze vragen in de app Energie InZicht voorgelegd. In een casestudie werd door één deelnemer de studieduur verlengd naar 101 dagen. Bij start van de psycho-oncologische zorg ontvingen alle deelnemers gepersonaliseerde feedback in de vorm van netwerken op basis van de verzamelde EMA-data die ze bespraken met hun therapeut om er samen betekenis aan te geven. Na uitgebreide evaluatie met patiënten en therapeuten, lijkt het gebruik van de EMA-dataverzameling met de app Energie InZicht tijdens de wachtlijst gevolgd door gepersonaliseerde netwerkfeedback bruikbaar en haalbaar om psycho-oncologische zorg op maat aan te bieden. Dit zou de gedeelde besluitvorming over de behandelrichting en het hoofddoel van de behandeling bij start van de psycho-oncologische zorg kunnen vergemakkelijken. Het is belangrijk om het ontwikkelen van gepersonaliseerde feedback te automatiseren. Daarnaast therapeuten te trainen in het bespreken van de netwerken en patiënt en therapeut eerst kennis te laten maken, zodat de terugkoppeling van de feedback optimaal is. Toekomstig onderzoek kan onderzoeken of het gebruik van de EMA-app Energie InZicht effectief is en ook zorgt voor een kortere behandelduur. SUMMARY ENGLISH Principal findings In this thesis, I explored the patient perspective on CCRF. I used idiographic and phenomenological methodologies to investigate how patients experience and respond to CCRF. This experiential knowledge of CCRF combined with network theory applied to EMA data are used to find an answer to the central research question: in what way(s) can we personalize psycho-oncological care for patients with CCRF? In the following paragraphs, I summarize the findings of five studies. The summary is followed by a critical reflection on the main results of this thesis to put them in a broader context, a discussion of the methodological strengths and limitations of the presented idiographic research, and an outline of the recommendations for clinical psycho-oncological practice and future research. Chapter 2: Experiencing and responding to chronic cancer-related fatigue: A metaethnography of qualitative research Chapter 2 consists of a meta-ethnography of qualitative studies, which included patients who suffered from CCRF. The aim of this meta-ethnography was to create an overarching interpretative narrative that focused on how patients’ experience and respond to CCRF. I performed a comprehensive systematic literature search. Of the 1178 selected studies, I included sixteen qualitative studies after deduplication and abstract and full-text screening. These studies included 705 patients (majority women) with different ages, cancer types (mainly breast cancer), stages, and (phase of) treatment(s). The quality of the included studies was variable according to the appraisal with the CASP criteria for qualitative research.1 I followed the seven phases of meta-ethnography first described by Noblit and Hare to extract and translate the first-order constructs (patients’ interpretations) and second-order constructs (authors’ interpretations) from the studies and synthesize these into third-order constructs (new interpretations).2 This interpretative qualitative review that focused on how patients experience and respond to CCRF showed an embodied structure of CCRF. I developed a figure of embodied CCRF (see figure 2 in Chapter 2) that consists of six interrelated third-order constructs with social, spatial and temporal dimensions: 1. Embodied experience: the negative awareness of the body; 2. (Mis)Recognition: the lack of recognition by patients, relatives and health professionals (social dimension);3. Small horizon: a narrowed world perspective (spatial dimension); 4. Role change: adopting other life roles (social dimension); 5. Loss of self: the impact on identity (temporal dimension); 6. Regaining one’s footing: the process of responding to CCRF by struggling, adapting and accepting (temporal dimension). These findings can help health professionals to recognize CCRF and take a person-centered approach. My first impression from psycho-oncological care practice is that the figure can be used as a tool to facilitate the communication between patients and health professionals. This can lead to recognition and normalization of the central problems, which can help patients to regain a sense of control. Chapter 3: Navigating severe chronic cancer-related fatigue: An interpretative phenomenological analysis In Chapter 3, I conducted semi-structured face-to-face interviews with adult participants who suffered from severe CCRF for at least three months after completion of cancer treatment. The purposively selected sample included a homogeneous sample of 25 participants. The aim of this interview study was to better understand the lived experiences of patients with severe CCRF. In this interview study, I used a theoretical framework of philosophical phenomenology to explore how patients with CCRF experience disruptions in embodiment, time, and space and how these are related.3–5 For qualitative analysis of the interviews, I followed the six steps of the IPA method of Smith.6 After discussion with our multidisciplinary research team, I identified four interrelated themes that expressed different dimensions of the embodied experience of CCRF: 1. Worn out: how CCRF is an overwhelming dynamic experience with different sensations (i.e., physical, emotional, sensory, and cognitive) in one’s body (e.g., limbs and/or mind), and could result in a loss of self (affective dimension); 2. Diminishment of one’s “I can”: how time and space to move ‘freely’ is restricted by the bodily experience of CCRF and impairs one’s activities and social life (functional dimension); 3. Invisibility: how the body with CCRF becomes an object within a social context because others cannot see CCRF (social and material dimension); 4. Regaining one’s “I can”: how one can adapt active time and movement in space to the embodied experience of CCRF, one’s limitations in functioning, and objectification of one’s body in a social context (functional and productive dimension).This phenomenological interview study showed that experiencing CCRF is a personal, complex, and dynamic process that consists of interconnected affective, social, material, functional, and productive dimensions. Chapter 4: Forming new habits in the face of chronic cancer-related fatigue: An interpretative phenomenological study In Chapter 4, I used the same interview sample of 25 participants with severe CCRF from Chapter 3 and focused on the question of what is helpful in responding to CCRF to facilitate adaptation. I followed the six steps of the IPA method of Smith:6 I identified five interrelated themes of the dynamic and mutually reinforcing habitual process of responding to CCRF: 1. Discovering physical and emotional boundaries: a learning process of selfmonitoring focused on how one’s body feels to protect boundaries and prevent exhaustion; 2. Communicating support needs: ways of searching for information and asking for (professional) help; 3. Reorganizing and planning activities and rest: finding a new way to balance activities and rest in one’s life; 4. Letting go of one’s habitual identity: stopping with old habits and changing one’s role into a less active person; 5. Recognizing and accepting CCRF: how the formation of new habitual ways to respond to CCRF creates room for new beliefs such as acceptance of one’s CCRF. This phenomenological interview study provided insight into what is helpful while responding to CCRF. In this process of habit formation, breaking with unhelpful habits and negative beliefs is essential. Chapter 5: Using smartphone-based ecological momentary assessment and personalized feedback for patients with chronic cancer-related fatigue: A proof-of-concept study A quantitative form of idiographic research is ecological momentary assessment (EMA), also called the experience sampling method. EMA is a structured diary technique, in which a participant receives questions (e.g., symptoms, affect, behavior) multiple times a day for multiple days on end in their daily living environment.7 Based on the findings from chapters 2-4 described above and from the perspective of the network theory as introduced in the first chapter, together with my colleagues, I developed the Energy InSight app, an EMA app specifically targeted at assessing CCRF idiographic as interrelated phenomenon. In Chapter 5, I conducted a proof-of-concept study implemented in routine psychooncological care with five participants on the waitlist for psychological treatment for severe CCRF and their therapists. Participants completed EMA questions (i.e., fatigue, mood, activity, coping with CCRF, and context) of the Energy InSight app on their mobile phone five times a day for a three-week period. In the following week they received personalized descriptive feedback from the researcher and during the first session with their therapist they discussed the network feedback together. The aims were to explore 1) to what extent and how a patient gained insight into CCRF by filling in the smartphone-based EMA and receiving personalized (network) feedback, and 2) how this insight can help patients and therapists improve the case conceptualization process in psycho-oncological care for CCRF. I used think-aloud interviews, semi-structured interviews, and observations to explore the user experiences of patients and their therapists. I performed inductive thematic analysis of the transcripts8. Based on patients’ and therapists’ experiences in this proof-of-concept study, using EMA data collection and discussing descriptive and network feedback seems feasible and usable to personalize and improve psycho-oncological care for CCRF. Patients’ experiences (N=5): The qualitative findings showed that using the EMA app (Energy InSight) for some patients resulted in negative reactions from others and increased the awareness of the body, (dis) abilities, and feelings. Using the EMA app (Energy InSight) and receiving the descriptive feedback report enabled for everyone visibility and acknowledgment of their main problem. The discussion of the descriptive and network feedback was emotionally confronting in a positive way for most patients. The descriptive and network feedback helped all patients to identify and recognize interrelated problems of CCRF. Using the EMA app (Energy InSight), followed by the descriptive feedback initiated for some patients a change in their behavior to respond to CCRF in helpful ways. The discussion of the network feedback report helped all patients to set treatment goals or change treatment direction. Therapists’ experiences (N=4): The qualitative findings demonstrated that some therapists reported limited use of the descriptive reports. Most therapists evaluated the network feedback as insightful, useful, and an accelerator in treatment to identify the main problems. However, exploring network associations and translating the findings to practical use in psycho-oncological care was challenging for all therapists. Chapter 6: Personalizing psychological care for chronic cancer-related fatigue: A case study on symptom dynamics In Chapter 6, I presented a case study to illustrate how feedback on person-specific networks can provide new insight into CCRF and how these insights can aid personalization of psychological treatment of CCRF. This case was part of the proof-of-concept study (Chapter 5). A 34-year-old woman with CCRF as her main problem was referred to a mental health institute for psycho-oncology. During the time on the waitlist, she completed the EMA questionnaire (Energy InSight) with 24 questions about fatigue, mood, activity, coping with fatigue, and context five times a day. She was willing to fill out the EMA app for 101 days. This allowed us to explore both moment-level and day-level partial (directed) correlation networks and to gain more insights into how symptom dynamics can change over time. The interplay between symptoms, cognitions and behavior was visualized in the personspecific moment-level and day-level networks, which were discussed with the patient. For example, accepting fatigue was an important node in the moment-level and day-level contemporaneous network. In the moment-level network, acceptance of fatigue in the last three hours had a connection with less hopelessness in the past three hours and less fatigue in the following moment. In the day-level contemporaneous network, acceptance was associated with less fatigue, less hopelessness, better mood, and more motivation to do things on the same day. The patient recognized this pattern. She explained that the unpredictability of CCRF can make her feel hopeless. These findings opened a dialogue with the patient about the importance of acceptance in responding to fatigue. She discussed these findings with her therapist. This case study demonstrated how symptom networks can provide insights into how to better respond to fatigue and might help to find a direction for treatment

Using the patient perspective to personalize psycho-oncological care for chronic cancer-related fatigue

Ongeveer een kwart van alle mensen met kanker ervaart chronische kanker-gerelateerde vermoeidheid (CKV) nadat de behandeling voor kanker is afgerond. Patiënten met CKV worden beperkt in hun dagelijkse activiteiten. Eerder onderzoek naar CKV richtte zich vooral op vrouwen met borstkanker tijdens de behandeling voor kanker en niet-helpende factoren van CKV. Ook werd in grote groepen onderzoek gedaan naar effectiviteit van psychosociale behandelingen voor CKV. Er is echter nog onvoldoende bekend over welke behandeling het beste werkt voor wie.Om dit te onderzoeken, werd in dit proefschrift onderzoek uitgevoerd bij het Helen Dowling Instituut naar ervaringen van het individu met CKV. Als eerste werd een overkoepelend overzicht gemaakt van zestien studies naar ervaringen en omgaan met CKV. Hieruit kwam naar voren dat het lichaam centraal staat in hoe patiënten CKV ervaren en ermee omgaan. Ook werden interviews afgenomen bij een diverse groep van 25 mensen met ernstige CKV om meer inzicht te krijgen in hoe CKV in het lichaam ervaren wordt. Deze mensen hadden verschillende vormen van kanker en kregen hiervoor verschillende behandelingen. De onzichtbaarheid van CKV en het chronisch vermoeide lichaam stonden vaak op een negatieve manier op de voorgrond, waardoor dagelijkse en sociale activiteiten niet langer mogelijk waren om te kunnen doen. Verder werd tijdens de interviews ook gevraagd naar wat kan helpen bij het omgaan met CKV, waarbij het vormen van nieuwe helpende gewoontes en acceptatie van CKV belangrijk bleek. De netwerkbenadering kijkt naar relaties tussen verschillende relevante factoren. Hierdoor is het mogelijk om met intensieve longitudinale dataverzameling binnen het individu te onderzoeken hoe het netwerk van factoren en CKV eruitziet voor die persoon. Door met behulp van netwerkanalyses te kijken naar het individuele netwerk, wordt inzicht verkregen in wat voor die persoon helpende en minder helpende factoren zijn en kan de behandeling daarop afgestemd worden. In een proof-of-concept studie werd deze netwerkbenadering toegepast en alle ervaringskennis, therapeutische ervaring en eerder onderzoek naar groepen patiënten met CKV samengebracht. Er werden 24 vragen over symptomen, emoties, helpende en niet-helpende manieren van omgaan met CKV en context geprogrammeerd als ‘Ecological Momentary Assessment’ (EMA)-app Energie InZicht. Vijf patiënten met als hoofdprobleem CKV op de wachtlijst voor psycho-oncologische zorg bij het Helen Dowling Instituut kregen vijf keer per dag gedurende drie weken op hun mobiele telefoon deze vragen in de app Energie InZicht voorgelegd. In een casestudie werd door één deelnemer de studieduur verlengd naar 101 dagen. Bij start van de psycho-oncologische zorg ontvingen alle deelnemers gepersonaliseerde feedback in de vorm van netwerken op basis van de verzamelde EMA-data die ze bespraken met hun therapeut om er samen betekenis aan te geven. Na uitgebreide evaluatie met patiënten en therapeuten, lijkt het gebruik van de EMA-dataverzameling met de app Energie InZicht tijdens de wachtlijst gevolgd door gepersonaliseerde netwerkfeedback bruikbaar en haalbaar om psycho-oncologische zorg op maat aan te bieden. Dit zou de gedeelde besluitvorming over de behandelrichting en het hoofddoel van de behandeling bij start van de psycho-oncologische zorg kunnen vergemakkelijken. Het is belangrijk om het ontwikkelen van gepersonaliseerde feedback te automatiseren. Daarnaast therapeuten te trainen in het bespreken van de netwerken en patiënt en therapeut eerst kennis te laten maken, zodat de terugkoppeling van de feedback optimaal is. Toekomstig onderzoek kan onderzoeken of het gebruik van de EMA-app Energie InZicht effectief is en ook zorgt voor een kortere behandelduur. SUMMARY ENGLISH Principal findings In this thesis, I explored the patient perspective on CCRF. I used idiographic and phenomenological methodologies to investigate how patients experience and respond to CCRF. This experiential knowledge of CCRF combined with network theory applied to EMA data are used to find an answer to the central research question: in what way(s) can we personalize psycho-oncological care for patients with CCRF? In the following paragraphs, I summarize the findings of five studies. The summary is followed by a critical reflection on the main results of this thesis to put them in a broader context, a discussion of the methodological strengths and limitations of the presented idiographic research, and an outline of the recommendations for clinical psycho-oncological practice and future research. Chapter 2: Experiencing and responding to chronic cancer-related fatigue: A metaethnography of qualitative research Chapter 2 consists of a meta-ethnography of qualitative studies, which included patients who suffered from CCRF. The aim of this meta-ethnography was to create an overarching interpretative narrative that focused on how patients’ experience and respond to CCRF. I performed a comprehensive systematic literature search. Of the 1178 selected studies, I included sixteen qualitative studies after deduplication and abstract and full-text screening. These studies included 705 patients (majority women) with different ages, cancer types (mainly breast cancer), stages, and (phase of) treatment(s). The quality of the included studies was variable according to the appraisal with the CASP criteria for qualitative research.1 I followed the seven phases of meta-ethnography first described by Noblit and Hare to extract and translate the first-order constructs (patients’ interpretations) and second-order constructs (authors’ interpretations) from the studies and synthesize these into third-order constructs (new interpretations).2 This interpretative qualitative review that focused on how patients experience and respond to CCRF showed an embodied structure of CCRF. I developed a figure of embodied CCRF (see figure 2 in Chapter 2) that consists of six interrelated third-order constructs with social, spatial and temporal dimensions: 1. Embodied experience: the negative awareness of the body; 2. (Mis)Recognition: the lack of recognition by patients, relatives and health professionals (social dimension);3. Small horizon: a narrowed world perspective (spatial dimension); 4. Role change: adopting other life roles (social dimension); 5. Loss of self: the impact on identity (temporal dimension); 6. Regaining one’s footing: the process of responding to CCRF by struggling, adapting and accepting (temporal dimension). These findings can help health professionals to recognize CCRF and take a person-centered approach. My first impression from psycho-oncological care practice is that the figure can be used as a tool to facilitate the communication between patients and health professionals. This can lead to recognition and normalization of the central problems, which can help patients to regain a sense of control. Chapter 3: Navigating severe chronic cancer-related fatigue: An interpretative phenomenological analysis In Chapter 3, I conducted semi-structured face-to-face interviews with adult participants who suffered from severe CCRF for at least three months after completion of cancer treatment. The purposively selected sample included a homogeneous sample of 25 participants. The aim of this interview study was to better understand the lived experiences of patients with severe CCRF. In this interview study, I used a theoretical framework of philosophical phenomenology to explore how patients with CCRF experience disruptions in embodiment, time, and space and how these are related.3–5 For qualitative analysis of the interviews, I followed the six steps of the IPA method of Smith.6 After discussion with our multidisciplinary research team, I identified four interrelated themes that expressed different dimensions of the embodied experience of CCRF: 1. Worn out: how CCRF is an overwhelming dynamic experience with different sensations (i.e., physical, emotional, sensory, and cognitive) in one’s body (e.g., limbs and/or mind), and could result in a loss of self (affective dimension); 2. Diminishment of one’s “I can”: how time and space to move ‘freely’ is restricted by the bodily experience of CCRF and impairs one’s activities and social life (functional dimension); 3. Invisibility: how the body with CCRF becomes an object within a social context because others cannot see CCRF (social and material dimension); 4. Regaining one’s “I can”: how one can adapt active time and movement in space to the embodied experience of CCRF, one’s limitations in functioning, and objectification of one’s body in a social context (functional and productive dimension).This phenomenological interview study showed that experiencing CCRF is a personal, complex, and dynamic process that consists of interconnected affective, social, material, functional, and productive dimensions. Chapter 4: Forming new habits in the face of chronic cancer-related fatigue: An interpretative phenomenological study In Chapter 4, I used the same interview sample of 25 participants with severe CCRF from Chapter 3 and focused on the question of what is helpful in responding to CCRF to facilitate adaptation. I followed the six steps of the IPA method of Smith:6 I identified five interrelated themes of the dynamic and mutually reinforcing habitual process of responding to CCRF: 1. Discovering physical and emotional boundaries: a learning process of selfmonitoring focused on how one’s body feels to protect boundaries and prevent exhaustion; 2. Communicating support needs: ways of searching for information and asking for (professional) help; 3. Reorganizing and planning activities and rest: finding a new way to balance activities and rest in one’s life; 4. Letting go of one’s habitual identity: stopping with old habits and changing one’s role into a less active person; 5. Recognizing and accepting CCRF: how the formation of new habitual ways to respond to CCRF creates room for new beliefs such as acceptance of one’s CCRF. This phenomenological interview study provided insight into what is helpful while responding to CCRF. In this process of habit formation, breaking with unhelpful habits and negative beliefs is essential. Chapter 5: Using smartphone-based ecological momentary assessment and personalized feedback for patients with chronic cancer-related fatigue: A proof-of-concept study A quantitative form of idiographic research is ecological momentary assessment (EMA), also called the experience sampling method. EMA is a structured diary technique, in which a participant receives questions (e.g., symptoms, affect, behavior) multiple times a day for multiple days on end in their daily living environment.7 Based on the findings from chapters 2-4 described above and from the perspective of the network theory as introduced in the first chapter, together with my colleagues, I developed the Energy InSight app, an EMA app specifically targeted at assessing CCRF idiographic as interrelated phenomenon. In Chapter 5, I conducted a proof-of-concept study implemented in routine psychooncological care with five participants on the waitlist for psychological treatment for severe CCRF and their therapists. Participants completed EMA questions (i.e., fatigue, mood, activity, coping with CCRF, and context) of the Energy InSight app on their mobile phone five times a day for a three-week period. In the following week they received personalized descriptive feedback from the researcher and during the first session with their therapist they discussed the network feedback together. The aims were to explore 1) to what extent and how a patient gained insight into CCRF by filling in the smartphone-based EMA and receiving personalized (network) feedback, and 2) how this insight can help patients and therapists improve the case conceptualization process in psycho-oncological care for CCRF. I used think-aloud interviews, semi-structured interviews, and observations to explore the user experiences of patients and their therapists. I performed inductive thematic analysis of the transcripts8. Based on patients’ and therapists’ experiences in this proof-of-concept study, using EMA data collection and discussing descriptive and network feedback seems feasible and usable to personalize and improve psycho-oncological care for CCRF. Patients’ experiences (N=5): The qualitative findings showed that using the EMA app (Energy InSight) for some patients resulted in negative reactions from others and increased the awareness of the body, (dis) abilities, and feelings. Using the EMA app (Energy InSight) and receiving the descriptive feedback report enabled for everyone visibility and acknowledgment of their main problem. The discussion of the descriptive and network feedback was emotionally confronting in a positive way for most patients. The descriptive and network feedback helped all patients to identify and recognize interrelated problems of CCRF. Using the EMA app (Energy InSight), followed by the descriptive feedback initiated for some patients a change in their behavior to respond to CCRF in helpful ways. The discussion of the network feedback report helped all patients to set treatment goals or change treatment direction. Therapists’ experiences (N=4): The qualitative findings demonstrated that some therapists reported limited use of the descriptive reports. Most therapists evaluated the network feedback as insightful, useful, and an accelerator in treatment to identify the main problems. However, exploring network associations and translating the findings to practical use in psycho-oncological care was challenging for all therapists. Chapter 6: Personalizing psychological care for chronic cancer-related fatigue: A case study on symptom dynamics In Chapter 6, I presented a case study to illustrate how feedback on person-specific networks can provide new insight into CCRF and how these insights can aid personalization of psychological treatment of CCRF. This case was part of the proof-of-concept study (Chapter 5). A 34-year-old woman with CCRF as her main problem was referred to a mental health institute for psycho-oncology. During the time on the waitlist, she completed the EMA questionnaire (Energy InSight) with 24 questions about fatigue, mood, activity, coping with fatigue, and context five times a day. She was willing to fill out the EMA app for 101 days. This allowed us to explore both moment-level and day-level partial (directed) correlation networks and to gain more insights into how symptom dynamics can change over time. The interplay between symptoms, cognitions and behavior was visualized in the personspecific moment-level and day-level networks, which were discussed with the patient. For example, accepting fatigue was an important node in the moment-level and day-level contemporaneous network. In the moment-level network, acceptance of fatigue in the last three hours had a connection with less hopelessness in the past three hours and less fatigue in the following moment. In the day-level contemporaneous network, acceptance was associated with less fatigue, less hopelessness, better mood, and more motivation to do things on the same day. The patient recognized this pattern. She explained that the unpredictability of CCRF can make her feel hopeless. These findings opened a dialogue with the patient about the importance of acceptance in responding to fatigue. She discussed these findings with her therapist. This case study demonstrated how symptom networks can provide insights into how to better respond to fatigue and might help to find a direction for treatment

FAMOCA, Family online counseling for families with parental cancer

Parental cancer is a huge challenge to affected patients and their families. Often, affected parents of minor children are totally overwhelmed by the new diagnosis and need support, particularly concerning the communication with their spouse and children. Therefore, the aim of this research project was the evaluation of the feasibility and the effects of a web-based counseling intervention during the first months of cancer treatment, aimed at the improvement of coping at the level of children, couples, and the family. Publication 1 describes the set-up of the web-based program in a family affected by parental cancer immediately after diagnosis. The web-based program consisted of four modules of four weeks each, individualized for each family member. The publication demonstrates that web-based counseling is a feasible option for all family members with parental cancer. Publication 2 focuses on the feasibility of the web-based program and its effects on participating children. The children’s first stage adjustment to parental cancer did not show detrimental patterns. The major “lesson learned” in this setting was the challenge to contact and motivate families in need, not only starting, but also keeping up on the program. Publication 3 examined the feasibility and the effects on psychological adjustment focusing on challenges of the couple, using psychometric testing in patients and their partners before and after initial therapy, both on the program and on the control group. No comparisons to controls were possible. Signs of anxiety were present in patients and partners in the first phase of cancer treatment. A slight improvement in anxiety and psychological wellbeing was shown at follow-up. Taken together, feasibility was shown, but the effects on participants in this web-based counseling intervention could not be compared to controls due to low numbers in both groups