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 Danksagung
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:82894 |
| Date | 12 January 2023 |
| Creators | Hentschel, Ludwig Leopold |
| Contributors | Mehnert-Theuerkauf, Anja, Schuler, Markus, Platzbecker, Uwe, Goerling, Ute, Universität Leipzig, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/acceptedVersion, doc-type:doctoralThesis, info:eu-repo/semantics/doctoralThesis, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
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