Incorporating the patient’s voice into cancer care – Patient-reported outcomes from mere assessment to clinical practice

Throughout the last decades, evolving treatment-opportunities provide a better chance of cure and thereby a higher percentage of patients is being treated for chronic disease (Robert Koch Institut, 2016). As treatment-toxicity, side effects and disease-derived symptoms remain high, it has become crucial to assesses parameters reflecting patients’ perspective, instead of solely focusing on illness-centered outcomes such as survival or treatment response. During the last decades, Patient-reported outcomes (PROs) are on the rise throughout research and cancer care as a key component to capture a patient’s perspective. This work illustrates the broad framework that PROs can be conducted in. We gathered experience and pioneered a systematic PRO-assessment in routine outpatient care, which continues to be updated. We identified a suitable PRO-based geriatric screening tool to avoid a time and resource consuming comprehensive geriatric assessment. Furthermore, we explored the beneficial effects of a PRO-based tailored intervention on HRQoL and provided effect-size estimations. Assessing PROs yields many benefits throughout the care pathway (Andreassen et al., 2006; Basch et al., 2016; Kofoed et al., 2012; Velikova et al., 2004; Yang et al., 2018) and was shown to be feasible in different entities and treatment setting (Bennett et al., 2016; M. K. Schuler et al., 2016; Strasser et al., 2016; Warrington et al., 2019). As a strikingly large discordance between patients’ and clinicians’ perception of symptoms exists (Atkinson et al., 2016), PROs can increase the accuracy of detection of adverse events and even predict survival (Efficace et al., 2021). Based on these advantages, the EMA and the FDA advocate the use of PROs as endpoints in cancer research (European Medicines Agency, 2016; U.S. Department of Health and Human Services FDA Center for Drug Evaluation and Research et al., 2006). Throughout previous years, methodological progress has been made resulting in elaborated measurement technics such as computerized adaptive testing being applied to PRO-instruments (Petersen et al., 2018, 2020). Clinical usability was increased with development of summary scores, cut-off values and emerging normative data (Giesinger et al., 2016, 2020). Interventions based on PROs are promising (Ishaque et al., 2019; Kotronoulas et al., 2014). Despite this ever increasing body of literature on PRO, a significant number of questions remain unanswered. Firstly, there was scarce knowledge about the benefits of a PRO-based intervention in sarcoma patients as there was limited PRO-data available in this entity. Sarcomas are rare diseases, still accounting for slightly less than 1% of all malignant neoplasia worldwide. The age adjusted incidence ranged from 7.4 per 100.000 men and 6.6 per women in Germany (Ressing et al., 2018). As sarcoma-treatment is improving, side-effects and toxicity remain to occur frequently (Gough et al., 2011; McDonough et al., 2019; Reichardt et al., 2012; Storey et al., 2019; Winnette et al., 2017). Until recently, there was quite limited knowledge about the patient-reported burden in terms of HRQoL, symptoms and psychological distress in patients with STS (Tang et al., 2012). PRO-based interventions yield beneficial effects in different cancer entities. Nevertheless, the effects of a PRO-based intervention in STS-patients was scarcely explored. The YonLife-Study (Publication B, Hentschel et al., 2020) contributes new evidence that a PRO-based intervention yields beneficial effects on HRQoL and suggests a positive, yet non-significant effect on survival. Concerning symptoms, the results of the YonLife-intervention remain far from being encouraging. As effects sizes are available now, RCTs which are powered to a confirmatory purpose could be performed in this population. Secondly, the importance of PROs are emphasized by authorities such as EMA or FDA that emphasize the need to incorporate PRO in scientific studies. Yet during the early 2010s, the actual incorporation of PROs in clinical routine was limited in Germany. We therefore designed and established a routine assessment of PROs (Publication C, (Trautmann, Hentschel et al., 2016) incorporating the automatized calculation, comparison with normative or threshold data and implemented it to our hospital information system. As until recently, feasibility data such for such an intervention is scarce, we collect measures of adherence, required time and barriers reported by staff. For the clinical benefit, the established PRO-assessment is being developed further and expanded to other departments and clinics of our institution. Thirdly, as numbers of geriatric cancer patients rise (Le Saux et al., 2019), older patients continue to be underrepresented in clinical trials (Singh et al., 2017), therefore an immense lack of knowledge on treatment-toxicities and side effects in this population exists. Treatment needs to be adapted to older patients frailty-level, which can be conducted applying a time- and resource consuming Comprehensive Geriatric Assessment (Le Saux et al., 2019). Still, there is no consensus on which domains to include and how to measure them (Hamaker, Jonker, et al., 2012). A geriatric screening can alleviate burden of conducting a whole CGA. Several screening instruments exists, yet there is inconsistent data (Kotzerke et al., 2019; Mohile et al., 2018; Soubeyran et al., 2014) which tool yields the best predictive performance. Our project aimed to compare three of the available screening tools (VES-13, G8, POT/CARG). Being far from having a perfect predictive performance, the POT/CARG occurs to be the screening instrument with a high sensitivity and sufficient negative predictive value. Furthermore, our research supports the increasing evidence that ultra-short-screeners such as ECOG state or age bear only insufficient predictive performance.:1. Introduction 1.1 What are Patient-reported outcomes (PROs)? 1.2 Assessment of PROs 1.2.1 Feasible in clinical routine, improving relevant outcomes 1.2.2 Improving diagnostic accuracy 1.2.3 Supporting drug development 1.2.4 Evolving measurement techniques and standardization 1.3 PRO-based feedback interventions 1.4 PRO-based geriatric screening 1.5 Research needs 1.5.1 Identifying a suitable geriatric screener 1.5.2 Limited PRO-data on Soft-Tissue Sarcoma (STS) patients 1.5.3 Feasibility-research in routine care 1.6 study aims 2. Methods 2.1 Design and Sample of Publication A 2.2 Design and Sample of Publication B 2.3 Design and Sample of Publication C 2.4 Instruments 2.5 Non-PRO-Outcomes 2.5.1 Predictive performance 2.5.2 Survival analysis 2.5.3 Feasibility analysis 2.6 Statistical Analysis 2.6.1 Sample Size Estimation 2.6.2 Non-participation and drop-out analysis 2.6.3 Regression Analyses 2.6.4 Statistical software 2.6.5 Statistical analysis plans 3. Outline of Publications Publication A Publication B Publication C 4. Discussion 4.1 Main findings, integration in existing research and research implications 4.1.1 Geriatric screening tools 4.1.2 PROs in soft tissue sarcoma (STS) 4.1.3 Implementation of PROs into routine care 4.2 Strengths and Limitations 4.2.1 Strengths 4.2.2 Limitations 5. Conclusions 6. Summary 7. References 8. Appendix 8.1 Darstellung des eigenen Beitrags 8.1.1 Darstellung des eigenen Beitrags zur Publikation A 8.1.2 Darstellung des eigenen Beitrags zur Publikation B 8.1.3 Darstellung des eigenen Beitrags zur Publikation C 8.2 Erklärung über die eigenständige Abfassung der Arbeit 8.3 Curriculum Vitae 8.4 Publikationsverzeichnis 8.5 Danksagun

Financial toxicity in sarcoma patients and survivors in Germany : results from the multicenter PROSa study

Purpose Cancer patients have been shown to frequently suffer from financial burden before, during, and after treatment. However, the financial toxicity of patients with sarcoma has seldom been assessed. Therefore, the aim of this study was to evaluate whether financial toxicity is a problem for sarcoma patients in Germany and identify associated risk factors. Methods Patients for this analysis were obtained from a multicenter prospective cohort study conducted in Germany. Using the financial difficulties scale of the EORTC QLQ-C30, financial toxicity was considered to be present if the score exceeded a pre-defined threshold for clinical importance. Comparisons to an age- and sex-matched norm population were performed. A multivariate logistic regression using stepwise backward selection was used to identify factors associated with financial toxicity. Results We included 1103 sarcoma patients treated in 39 centers and clinics; 498 (44.7%) patients reported financial toxicity. Sarcoma patients had 2.5 times the odds of reporting financial difficulties compared to an age- and sex-matched norm population. Patient age  52.5 years, higher education status, higher income, and disease progression (compared to patients with complete remission) were associated with lower odds of reporting financial toxicity. Receiving a disability pension, being currently on sick leave, and having a disability pass were statistically significantly associated with higher odds of reporting financial toxicity. Conclusion Financial toxicity is present in about half of German sarcoma patients, making it a relevant quality of life topic for patients and decision-makers

Working situation and burden of work limitations in sarcoma patients : results from the multi-center prospective PROSa study

Purpose We investigated predictors of limitations in work performance, odds of drop out of work, and odds of receiving disability pension in sarcoma patients. Methods We measured clinical and sociodemographic data in adult sarcoma patients and recorded if the patients received a (1) disability pension at baseline or (2) had dropped out of work 1 year after initial assessment. (3) Work limitations were assessed using the Work-limitations questionnaire (WLQ©). We analyzed exploratively. Results (1) Amongst 364 analyzed patients, odds to receive a disability pension were higher in patients with abdominal tumors, older patients, high grade patients and with increasing time since diagnosis. (2) Of 356 patients employed at baseline, 21% (n = 76) had dropped out of work after 1 year. The odds of dropping out of work were higher in bone sarcoma patients and in patients who received additive radiotherapy ± systemic therapy compared with patients who received surgery alone. Odds of dropping out of work were less amongst self-employed patients and dropped with increasing time since diagnosis. (3) Work limitations were higher in woman and increased with age. Patients with bone and fibrous sarcomas were more affected than liposarcoma patients. Patients with abdominal tumors reported highest restrictions. Sarcoma treatment in the last 6 months increased work limitations. Conclusion Work limitations, drop out of work and dependence on a disability pension occurs frequently in patients with sarcoma adding to the burden of this condition. We were able to identify vulnerable groups in both the socioeconomic and disease categories

Developing Symptom Lists for People with Cancer Treated with Targeted Therapies

Background: Targeted Therapies (TTs) have revolutionised cancer treatment with their enhanced specificity of action. Compared with conventional therapies, TTs are delivered over a longer period and often have unusual symptom profiles. Patient reported outcome measures such as symptom side-effect lists need to be developed in a time-efficient manner to enable a rapid and full evaluation of new treatments and effective clinical managementObjective: the aim of this study is to develop a set of TT-related symptoms and identify the optimal method for developing symptom lists. Patients and Methods: symptoms from TT treatment in the context of Chronic Myeloid Leukaemia (CML), HER2 positive breast cancer, or Gastrointestinal Stromal Tumours (GIST) were identified through literature reviews, interviews with health care professionals (HCPs) and patients, and patient focus groups. The symptom set was then pilot tested in patients across the three cancer diagnoses: The number of items derived from each source (literature, patients, or HCPs) were compared. Results: a total of 316 patients and 86 HCPs from 16 countries participated. An initial set of 209 symptoms was reduced to 61 covering 12 symptom categories. Patient interviews made the greatest contribution to the item set.Conclusions: symptom lists should be created based on input from patients. The item set described will be applicable to the assessment of new TTs, and in monitoring treatment.<br/

Health related Quality of Life over time in German sarcoma patients. An analysis of associated factors - results of the PROSa study

Introduction Sarcomas are rare cancers and very heterogeneous in their location, histological subtype, and treatment. Health-Related Quality of Life (HRQoL) of sarcoma patients has rarely been investigated in longitudinal studies. Methods Here, we assessed adult sarcoma patients and survivors between September 2017 and February 2020, and followed-up for one year in 39 study centers in Germany. Follow-up time points were 6 (t1) and 12 months (t2) after inclusion. We used a standardized, validated questionnaire (the European Organisation for Research and Treatment of Cancer Quality of Life Core Instrument (EORTC QLQ-C30) and explored predictors of HRQoL in two populations (all patients (Analysis 1), patients in ongoing complete remission (Analysis 2)) using generalized linear mixed models. Results In total we included up to 1111 patients at baseline (915 at t1, and 847 at t2), thereof 387 participants were in complete remission at baseline (334 at t1, and 200 at t2). When analyzing all patients, HRQoL differed with regard to tumor locations: patients with sarcoma in lower extremities reported lower HRQoL values than patients with sarcomas in the upper extremities. Treatment which included radiotherapy and/or systemic therapy was associated with lower HRQoL. For patients in complete remission, smoking was associated with worse HRQoL-outcomes. In both analyses, bone sarcomas were associated with the worst HRQoL values. Being female, in the age group 55-&lt;65 years, having lower socioeconomic status, and comorbidities were all associated with a lower HRQoL, in both analyses. Discussion HRQoL increased partially over time since treatment and with sporting activities. HRQoL improved with time since treatment, although not in all domains, and was associated with lifestyle and socioeconomic factors. Bone sarcomas were the most affected subgroup. Methods to preserve and improve HRQoL should be developed for sarcoma patients. </sec

Incorporating the patient voice in sarcoma research: How can we assess health-related quality of life in this heterogeneous group of patients? a study protocol

Sarcomas comprise 1% of adult tumors and are very heterogeneous. Long-lasting and cumulative treatment side-effects detract from the (progression-free) survival benefit of treatment. Therefore, it is important to assess treatment effectiveness in terms of patient-reported outcomes (PROs), including health-related quality of life (HRQoL) as well. However, questionnaires capturing the unique issues of sarcoma patients are currently lacking. Given the heterogeneity of the disease, the development of such an instrument may be challenging. The study aims to (1) develop an exhaustive list of all HRQoL issues relevant to sarcoma patients and determine content validity; (2) determine a strategy for HRQoL measurement in sarcoma patients. We will conduct an international, multicenter, mixed-methods study (registered at clinicaltrials.gov: NCT04071704) among bone or soft tissue sarcoma patients ≥18 years, using EORTC Quality of Life Group questionnaire development guidelines. First, an exhaustive list of HRQoL issues will be generated, derived from literature and patient (n = 154) and healthcare professional (HCP) interviews (n = 30). Subsequently, another group of sarcoma patients (n = 475) and HCPs (n = 30) will be asked to rate and prioritize the issues. Responses will be analyzed by priority, prevalence and range of responses for each item. The outcome will be a framework for tailored HRQoL measurement in sarcoma patients, taking into account sociodemographic and clinical variables

Incorporating the patient’s voice into cancer care – Patient-reported outcomes from mere assessment to clinical practice

Throughout the last decades, evolving treatment-opportunities provide a better chance of cure and thereby a higher percentage of patients is being treated for chronic disease (Robert Koch Institut, 2016). As treatment-toxicity, side effects and disease-derived symptoms remain high, it has become crucial to assesses parameters reflecting patients’ perspective, instead of solely focusing on illness-centered outcomes such as survival or treatment response. During the last decades, Patient-reported outcomes (PROs) are on the rise throughout research and cancer care as a key component to capture a patient’s perspective. This work illustrates the broad framework that PROs can be conducted in. We gathered experience and pioneered a systematic PRO-assessment in routine outpatient care, which continues to be updated. We identified a suitable PRO-based geriatric screening tool to avoid a time and resource consuming comprehensive geriatric assessment. Furthermore, we explored the beneficial effects of a PRO-based tailored intervention on HRQoL and provided effect-size estimations. Assessing PROs yields many benefits throughout the care pathway (Andreassen et al., 2006; Basch et al., 2016; Kofoed et al., 2012; Velikova et al., 2004; Yang et al., 2018) and was shown to be feasible in different entities and treatment setting (Bennett et al., 2016; M. K. Schuler et al., 2016; Strasser et al., 2016; Warrington et al., 2019). As a strikingly large discordance between patients’ and clinicians’ perception of symptoms exists (Atkinson et al., 2016), PROs can increase the accuracy of detection of adverse events and even predict survival (Efficace et al., 2021). Based on these advantages, the EMA and the FDA advocate the use of PROs as endpoints in cancer research (European Medicines Agency, 2016; U.S. Department of Health and Human Services FDA Center for Drug Evaluation and Research et al., 2006). Throughout previous years, methodological progress has been made resulting in elaborated measurement technics such as computerized adaptive testing being applied to PRO-instruments (Petersen et al., 2018, 2020). Clinical usability was increased with development of summary scores, cut-off values and emerging normative data (Giesinger et al., 2016, 2020). Interventions based on PROs are promising (Ishaque et al., 2019; Kotronoulas et al., 2014). Despite this ever increasing body of literature on PRO, a significant number of questions remain unanswered. Firstly, there was scarce knowledge about the benefits of a PRO-based intervention in sarcoma patients as there was limited PRO-data available in this entity. Sarcomas are rare diseases, still accounting for slightly less than 1% of all malignant neoplasia worldwide. The age adjusted incidence ranged from 7.4 per 100.000 men and 6.6 per women in Germany (Ressing et al., 2018). As sarcoma-treatment is improving, side-effects and toxicity remain to occur frequently (Gough et al., 2011; McDonough et al., 2019; Reichardt et al., 2012; Storey et al., 2019; Winnette et al., 2017). Until recently, there was quite limited knowledge about the patient-reported burden in terms of HRQoL, symptoms and psychological distress in patients with STS (Tang et al., 2012). PRO-based interventions yield beneficial effects in different cancer entities. Nevertheless, the effects of a PRO-based intervention in STS-patients was scarcely explored. The YonLife-Study (Publication B, Hentschel et al., 2020) contributes new evidence that a PRO-based intervention yields beneficial effects on HRQoL and suggests a positive, yet non-significant effect on survival. Concerning symptoms, the results of the YonLife-intervention remain far from being encouraging. As effects sizes are available now, RCTs which are powered to a confirmatory purpose could be performed in this population. Secondly, the importance of PROs are emphasized by authorities such as EMA or FDA that emphasize the need to incorporate PRO in scientific studies. Yet during the early 2010s, the actual incorporation of PROs in clinical routine was limited in Germany. We therefore designed and established a routine assessment of PROs (Publication C, (Trautmann, Hentschel et al., 2016) incorporating the automatized calculation, comparison with normative or threshold data and implemented it to our hospital information system. As until recently, feasibility data such for such an intervention is scarce, we collect measures of adherence, required time and barriers reported by staff. For the clinical benefit, the established PRO-assessment is being developed further and expanded to other departments and clinics of our institution. Thirdly, as numbers of geriatric cancer patients rise (Le Saux et al., 2019), older patients continue to be underrepresented in clinical trials (Singh et al., 2017), therefore an immense lack of knowledge on treatment-toxicities and side effects in this population exists. Treatment needs to be adapted to older patients frailty-level, which can be conducted applying a time- and resource consuming Comprehensive Geriatric Assessment (Le Saux et al., 2019). Still, there is no consensus on which domains to include and how to measure them (Hamaker, Jonker, et al., 2012). A geriatric screening can alleviate burden of conducting a whole CGA. Several screening instruments exists, yet there is inconsistent data (Kotzerke et al., 2019; Mohile et al., 2018; Soubeyran et al., 2014) which tool yields the best predictive performance. Our project aimed to compare three of the available screening tools (VES-13, G8, POT/CARG). Being far from having a perfect predictive performance, the POT/CARG occurs to be the screening instrument with a high sensitivity and sufficient negative predictive value. Furthermore, our research supports the increasing evidence that ultra-short-screeners such as ECOG state or age bear only insufficient predictive performance.:1. Introduction 1.1 What are Patient-reported outcomes (PROs)? 1.2 Assessment of PROs 1.2.1 Feasible in clinical routine, improving relevant outcomes 1.2.2 Improving diagnostic accuracy 1.2.3 Supporting drug development 1.2.4 Evolving measurement techniques and standardization 1.3 PRO-based feedback interventions 1.4 PRO-based geriatric screening 1.5 Research needs 1.5.1 Identifying a suitable geriatric screener 1.5.2 Limited PRO-data on Soft-Tissue Sarcoma (STS) patients 1.5.3 Feasibility-research in routine care 1.6 study aims 2. Methods 2.1 Design and Sample of Publication A 2.2 Design and Sample of Publication B 2.3 Design and Sample of Publication C 2.4 Instruments 2.5 Non-PRO-Outcomes 2.5.1 Predictive performance 2.5.2 Survival analysis 2.5.3 Feasibility analysis 2.6 Statistical Analysis 2.6.1 Sample Size Estimation 2.6.2 Non-participation and drop-out analysis 2.6.3 Regression Analyses 2.6.4 Statistical software 2.6.5 Statistical analysis plans 3. Outline of Publications Publication A Publication B Publication C 4. Discussion 4.1 Main findings, integration in existing research and research implications 4.1.1 Geriatric screening tools 4.1.2 PROs in soft tissue sarcoma (STS) 4.1.3 Implementation of PROs into routine care 4.2 Strengths and Limitations 4.2.1 Strengths 4.2.2 Limitations 5. Conclusions 6. Summary 7. References 8. Appendix 8.1 Darstellung des eigenen Beitrags 8.1.1 Darstellung des eigenen Beitrags zur Publikation A 8.1.2 Darstellung des eigenen Beitrags zur Publikation B 8.1.3 Darstellung des eigenen Beitrags zur Publikation C 8.2 Erklärung über die eigenständige Abfassung der Arbeit 8.3 Curriculum Vitae 8.4 Publikationsverzeichnis 8.5 Danksagun

Incorporating the patient’s voice into cancer care – Patient-reported outcomes from mere assessment to clinical practice

Throughout the last decades, evolving treatment-opportunities provide a better chance of cure and thereby a higher percentage of patients is being treated for chronic disease (Robert Koch Institut, 2016). As treatment-toxicity, side effects and disease-derived symptoms remain high, it has become crucial to assesses parameters reflecting patients’ perspective, instead of solely focusing on illness-centered outcomes such as survival or treatment response. During the last decades, Patient-reported outcomes (PROs) are on the rise throughout research and cancer care as a key component to capture a patient’s perspective. This work illustrates the broad framework that PROs can be conducted in. We gathered experience and pioneered a systematic PRO-assessment in routine outpatient care, which continues to be updated. We identified a suitable PRO-based geriatric screening tool to avoid a time and resource consuming comprehensive geriatric assessment. Furthermore, we explored the beneficial effects of a PRO-based tailored intervention on HRQoL and provided effect-size estimations. Assessing PROs yields many benefits throughout the care pathway (Andreassen et al., 2006; Basch et al., 2016; Kofoed et al., 2012; Velikova et al., 2004; Yang et al., 2018) and was shown to be feasible in different entities and treatment setting (Bennett et al., 2016; M. K. Schuler et al., 2016; Strasser et al., 2016; Warrington et al., 2019). As a strikingly large discordance between patients’ and clinicians’ perception of symptoms exists (Atkinson et al., 2016), PROs can increase the accuracy of detection of adverse events and even predict survival (Efficace et al., 2021). Based on these advantages, the EMA and the FDA advocate the use of PROs as endpoints in cancer research (European Medicines Agency, 2016; U.S. Department of Health and Human Services FDA Center for Drug Evaluation and Research et al., 2006). Throughout previous years, methodological progress has been made resulting in elaborated measurement technics such as computerized adaptive testing being applied to PRO-instruments (Petersen et al., 2018, 2020). Clinical usability was increased with development of summary scores, cut-off values and emerging normative data (Giesinger et al., 2016, 2020). Interventions based on PROs are promising (Ishaque et al., 2019; Kotronoulas et al., 2014). Despite this ever increasing body of literature on PRO, a significant number of questions remain unanswered. Firstly, there was scarce knowledge about the benefits of a PRO-based intervention in sarcoma patients as there was limited PRO-data available in this entity. Sarcomas are rare diseases, still accounting for slightly less than 1% of all malignant neoplasia worldwide. The age adjusted incidence ranged from 7.4 per 100.000 men and 6.6 per women in Germany (Ressing et al., 2018). As sarcoma-treatment is improving, side-effects and toxicity remain to occur frequently (Gough et al., 2011; McDonough et al., 2019; Reichardt et al., 2012; Storey et al., 2019; Winnette et al., 2017). Until recently, there was quite limited knowledge about the patient-reported burden in terms of HRQoL, symptoms and psychological distress in patients with STS (Tang et al., 2012). PRO-based interventions yield beneficial effects in different cancer entities. Nevertheless, the effects of a PRO-based intervention in STS-patients was scarcely explored. The YonLife-Study (Publication B, Hentschel et al., 2020) contributes new evidence that a PRO-based intervention yields beneficial effects on HRQoL and suggests a positive, yet non-significant effect on survival. Concerning symptoms, the results of the YonLife-intervention remain far from being encouraging. As effects sizes are available now, RCTs which are powered to a confirmatory purpose could be performed in this population. Secondly, the importance of PROs are emphasized by authorities such as EMA or FDA that emphasize the need to incorporate PRO in scientific studies. Yet during the early 2010s, the actual incorporation of PROs in clinical routine was limited in Germany. We therefore designed and established a routine assessment of PROs (Publication C, (Trautmann, Hentschel et al., 2016) incorporating the automatized calculation, comparison with normative or threshold data and implemented it to our hospital information system. As until recently, feasibility data such for such an intervention is scarce, we collect measures of adherence, required time and barriers reported by staff. For the clinical benefit, the established PRO-assessment is being developed further and expanded to other departments and clinics of our institution. Thirdly, as numbers of geriatric cancer patients rise (Le Saux et al., 2019), older patients continue to be underrepresented in clinical trials (Singh et al., 2017), therefore an immense lack of knowledge on treatment-toxicities and side effects in this population exists. Treatment needs to be adapted to older patients frailty-level, which can be conducted applying a time- and resource consuming Comprehensive Geriatric Assessment (Le Saux et al., 2019). Still, there is no consensus on which domains to include and how to measure them (Hamaker, Jonker, et al., 2012). A geriatric screening can alleviate burden of conducting a whole CGA. Several screening instruments exists, yet there is inconsistent data (Kotzerke et al., 2019; Mohile et al., 2018; Soubeyran et al., 2014) which tool yields the best predictive performance. Our project aimed to compare three of the available screening tools (VES-13, G8, POT/CARG). Being far from having a perfect predictive performance, the POT/CARG occurs to be the screening instrument with a high sensitivity and sufficient negative predictive value. Furthermore, our research supports the increasing evidence that ultra-short-screeners such as ECOG state or age bear only insufficient predictive performance.:1. Introduction 1.1 What are Patient-reported outcomes (PROs)? 1.2 Assessment of PROs 1.2.1 Feasible in clinical routine, improving relevant outcomes 1.2.2 Improving diagnostic accuracy 1.2.3 Supporting drug development 1.2.4 Evolving measurement techniques and standardization 1.3 PRO-based feedback interventions 1.4 PRO-based geriatric screening 1.5 Research needs 1.5.1 Identifying a suitable geriatric screener 1.5.2 Limited PRO-data on Soft-Tissue Sarcoma (STS) patients 1.5.3 Feasibility-research in routine care 1.6 study aims 2. Methods 2.1 Design and Sample of Publication A 2.2 Design and Sample of Publication B 2.3 Design and Sample of Publication C 2.4 Instruments 2.5 Non-PRO-Outcomes 2.5.1 Predictive performance 2.5.2 Survival analysis 2.5.3 Feasibility analysis 2.6 Statistical Analysis 2.6.1 Sample Size Estimation 2.6.2 Non-participation and drop-out analysis 2.6.3 Regression Analyses 2.6.4 Statistical software 2.6.5 Statistical analysis plans 3. Outline of Publications Publication A Publication B Publication C 4. Discussion 4.1 Main findings, integration in existing research and research implications 4.1.1 Geriatric screening tools 4.1.2 PROs in soft tissue sarcoma (STS) 4.1.3 Implementation of PROs into routine care 4.2 Strengths and Limitations 4.2.1 Strengths 4.2.2 Limitations 5. Conclusions 6. Summary 7. References 8. Appendix 8.1 Darstellung des eigenen Beitrags 8.1.1 Darstellung des eigenen Beitrags zur Publikation A 8.1.2 Darstellung des eigenen Beitrags zur Publikation B 8.1.3 Darstellung des eigenen Beitrags zur Publikation C 8.2 Erklärung über die eigenständige Abfassung der Arbeit 8.3 Curriculum Vitae 8.4 Publikationsverzeichnis 8.5 Danksagun

Electronic Patient Reported Outcome (ePRO) Measures in Patients with Soft Tissue Sarcoma (STS) Receiving Palliative Treatment

The PazoQoL prospective, randomized, controlled, multicenter study was designed to continuously assess global health related quality of life (HRQoL) during treatment with pazopanib or physician-preferred chemotherapy over a 9-week period. The questionnaires were completed by the patients at home with great reliability during this time period. Continuous electronic patient reported outcome (ePRO) enabled early detection of the onset of deterioration and timely initiation of countermeasures. The Cancer Therapy Satisfaction Questionnaire (CTSQ) showed high interindividual variability and decline over a 9-week period, whereas the Time Trade-off (TTO) proved to be an efficient method for assessing individual benefit from cancer therapy. In our cohort, the TTO clearly demonstrated that the prolongation of life and the side effect profile of continued therapy were not as satisfactory as expected by patients when starting a new therapy. Although the study had to be stopped early due to the pandemic, our findings could translate into clinical practice without much effort and outside of a trial