Search Results (37)

(1) Background: Quality of life (QoL) assessment is a crucial aspect for patients diagnosed with cancer. Over the years, different tools have been developed to measure QoL, both generic and pathology specific, but the inclusion of quality of life among other indicators of efficacy in randomized controlled trials (RCTs) remains a controversial issue. In this review, we aim to review the frequency and modality of QoL assessment in RCTs, enrolling patients diagnosed with mesenchymal tumors. (2) Methods: An electronic literature search of bone and soft tissue sarcoma and GIST-related RCTs published between January 2000 and December 2023 was performed by two independent reviewers using PubMed. English-language phase II and III clinical trials enrolling at least more than 15 patients were included, regardless of the disease stage. Studies involving patients under the age of 18 years or for which the full text was not available were excluded. For each study, data regarding the journal and year of publication, the study design, the primary objective, and the evaluation of quality of life as an endpoint with any type of patient-reported outcomes used were extracted. (3) Results: Among the 742 publications screened, 171 resulted eligible. QoL assessment was listed among the endpoints in 35 trials and QoL results were reported in 29 primary publications. In these trials, 16 included patients with soft tissue sarcomas, 8 Kaposi sarcomas, 6 GIST, and 3 desmoid tumors. Among all the trials included, 10.4% on an adjuvant/neoadjuvant setting and 24.4% on a metastatic setting included QoL as an endpoint. The proportion of trials, including QoL, was variable over time, as follows: 16.9% of trials in 2000–2014 vs. 23.4% in 2015–2023. In 35 trials, including QoL endpoints, 27 had a superiority design and 25 reported a positive result. In the majority of trials (80%), the tools for QoL assessment were generic and those mostly used were the EORTC QLQ-C30, the EQ-5D questionnaire, and the modified Brief Pain Inventory–Short Form. (4) Conclusions: Quality of life has not been assessed or published in many phase II and III trials, despite an improvement over time. QoL evaluation in RCTs should be considered even more carefully in patients with rare tumors, where the low number of patients who can be enrolled makes it difficult to draw statistically significant conclusions on the effectiveness of treatments. Full article

Background: Quality of life (QoL) is a critical indicator in assessing the success of oncological treatments for head and neck malignancies, reflecting their impact on physiological functions and psychosocial well-being beyond mere survival. Treatments (surgery, radiotherapy, chemotherapy) pose multiple functional and emotional challenges, and recent advancements underscore the necessity of evaluating post-treatment QoL. Objective: This literature review investigates the impact of oncological treatment on the QoL of patients with malignant head and neck cancers (oral, oropharyngeal, hypopharyngeal, laryngeal) and identifies factors influencing their QoL index. Methodology: Using a PICO framework, studies from PubMed Central were analyzed, selected based on inclusion (English publications, full text, PROM results) and exclusion criteria. The last research was conducted on 6 April 2025. From 231 identified studies, 49 were included after applying filters (MeSH: “Quality of Life,” “laryngeal cancer,” “oral cavity cancer,” etc.). Data were organized in Excel, and the methodology adhered to PRISMA standards. Results: Treatment Impact: Oncological treatments significantly affect QoL, with acute post-treatment declines in functions such as speech, swallowing, and emotional well-being (anxiety, depression). Partial recovery depends on rehabilitative interventions. Influencing Factors: Treatment type, disease stage, socioeconomic, and demographic contexts influence QoL. De-escalated treatments and prompt rehabilitation improve recovery, while complications like trismus, dysphagia, or persistent hearing issues reduce long-term QoL. Assessment Tools: Standardized PROM questionnaires (EORTC QLQ-C30, QLQ-H&N35, MDADI, HADS) highlighted QoL variations. Studies from Europe, North America, and Asia indicate regional differences in outcomes. Limitations: Retrospective designs, small sample sizes, and PROM variability limit generalizability. Multicentric studies with extended follow-up are recommended. Conclusions: Oncological treatments for head and neck malignancies have a complex impact on QoL, necessitating personalized and multidisciplinary strategies. De-escalated therapies, early rehabilitation, and continuous monitoring are essential for optimizing functional and psychosocial outcomes. Methodological gaps highlight the need for standardized research. Full article

Background/Objectives: Colorectal cancer is a significant health problem worldwide. Surgery is the primary curative treatment for most colorectal cancers. Cardiopulmonary exercise testing is now performed widely before surgery, and it is the most objective and precise means of evaluating pre-surgical physical fitness. Also, we can use the 6 min walk test to measure cardiorespiratory fitness before surgery. Methods: We included colorectal patients who were awaiting open abdominal or laparoscopic surgery. After admission to the hospital, patients who signed informed consent forms fulfilled a short questionnaire about health and physical status, preoperative physical activities, and quality of life questionnaire (EORTC QLQ-C30). Patients performed a 6 min walk test (6MWT) 2 days before surgery and 7 days after surgery. 6MWT is a tool for measuring the functional status of fitness. Also, they fulfilled the quality of recovery questionnaire (QoR 15) 7 days after surgery. Results: In a final analysis, we included 72 patients with a mean age of 62.48. We compared the number of steps, walk distance, average and maximal walk speed, and average and maximal heart rate before and after surgery, overall, and by group. Our findings show a statistically significant difference between men and women in the walk distance (F = 4.99, p = 0.02) The number of steps showed a statistically significant difference according to patients’ ages (F = 2.90, p = 0.02). Also, we detected differences in the average and maximum heart rate during walking when comparing body mass index (average heart rate F = 5.72, p = 0.00, maximum heart rate F = 2.52, p = 0.04). Conclusions: Our study provides evidence that average and maximal heart rate during the 6 min walk test was higher in the postoperative period, especially in overweight and obese participants. Full article

Background/Objectives: The management of oropharyngeal squamous cell carcinoma (OPSCC) often involves multidisciplinary decision-making to optimize patient outcomes. Surgery and chemoradiation therapy (CRT) represent the two main treatment modalities. The aim of this cross-sectional study was to provide a comprehensive analysis of quality of life, speech, swallowing, sleep, psychological distress, and nutritional status in OPSCC patients treated with either surgery or CRT. Methods: Thirty subjects were divided into two groups based on treatment modality (>12-month follow-up): (A) surgery ± adjuvant treatment (15 patients); (B) exclusive CRT (15 patients). A multidimensional evaluation was performed by means of validated questionnaires. The following parameters were analyzed: quality of life, speech, swallowing, sleep quality, risk of sleep apnea, sleepiness, psychological distress, pain, and nutritional status. Results: No statistically significant difference was found between the two study groups for every parameter. The EORTC QLQ-C30 globally showed a good quality of life in both groups. Poor sleep quality was observed in 9 (60%) subjects in group A and in 6 (40%) patients in group B, respectively. Low, intermediate and high risk of malnutrition was observed in 73.3%, 20.0% and 6.7% of cases in group A, and in 93.3%, 6.7% and 0.0% in group B, respectively. Conclusions: Surgery and exclusive chemoradiotherapy appear to yield similar long-term outcomes across all evaluated dimensions, including quality of life, speech, swallowing, sleep, psychological distress, and nutritional status. Full article

Background: Understanding the role of personality traits in shaping treatment outcomes is crucial given the multifaceted challenges posed by brain tumors and the significant adverse impact of radiotherapy (RT) on patients’ well-being. Purpose: This study aimed to provide insights into how personality traits affect psychosocial well-being and quality of life during RT in patients with high-grade malignant brain tumors. Methods: Personality traits in patients with high-grade glioma were assessed using the Eysenck Personality Questionnaire-Revised (EPQ-R). Quality of life was analyzed using EORTC questionnaires: the Questionnaire-Core 30 (QLQ-C30) and the Brain Cancer Module (QLQ-BN20). Patients were evaluated before RT, immediately after 6 weeks of RT, and 3 months post-RT. Results: Neuroticism predicted emotional function only three months post-RT. Extraversion decreased quality of life in global health status (third assessment), role function (second assessment), and emotional function (second and third assessments) but improved cognitive (first assessment) and social function (second assessment). The trait associated with lying was linked to a better quality of life in all domains except physical and cognitive function. Anxiety predicted a lower quality of life in brain tumor patients across all domains at various stages of RT treatment. Conclusions: This study advances our understanding of the psychosocial aspects of brain tumor care by highlighting the influence of personality traits on quality-of-life outcomes during RT. Identifying high-grade glioma patients at greater risk of a diminished quality of life based on personality profiles allows healthcare professionals to tailor interventions to address specific psychosocial needs, ultimately enhancing patient outcomes and holistic care during oncological treatment. Full article

(1) Background: Laryngeal surgery due to carcinoma leads to significant tissue disruption, cellular injury, and inflammation. This leads to increased levels of reactive oxygen species (ROS), causing oxidative damage that can influence quality of life (QOL) and recovery and complicate the postoperative course. The aim of this study was to compare how postoperative quality of life and surgical complication occurrence interacted with the biomarker levels of oxidative stress (malondialdehyde, MDA; superoxide dismutase, SOD; glutathione peroxidase 1, GPX1; and catalase, CAT) and inflammation (interleukin 1, IL-1; interleukin 6, IL-6; C-reactive protein, CRP) in patients treated with conservative and radical laryngeal surgery. (2) Methods: The study included 56 patients who underwent surgical treatment for laryngeal cancer. Blood samples were collected to analyze oxidative stress and inflammation parameters before surgery and on the first and seventh days postoperatively. Serum concentrations of MDA, SOD, GPX, CAT, IL-1, IL-6, and CRP were measured using coated enzyme-linked immunosorbent assay (ELISA) kits. EORTC QLQ-H&H43 questionnaire was used to measure the QOL of patients. (3) Results and Conclusions: T stage, pain intensity, and the extent of the surgical procedure were established as significant predictive factors for QOL in multivariate analysis. There was a significant positive correlation between surgical complication occurrence and preoperative values of GPX and MDA, but significant predictors of surgical complication occurrence on the 7th postoperative day were SOD and MDA values (p < 0.05). Full article

Purpose: To characterize dietary patterns and examine associations with cross-sectional and longitudinal changes in quality of life (QOL) over approximately one year after colorectal cancer (CRC) diagnosis. Methods: The ColoCare Study is an international, multi-center, prospective cohort study of newly diagnosed CRC survivors of any stage. A subset of participants with CRC in the United States completed patient-reported outcome measures at 6- and 12-months post-enrollment, including the Food Frequency Questionnaire (FFQ) and European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Dietary patterns at 6 months (around the time of treatment completion) were identified using Principal Component Analysis (PCA) with varimax rotation. Adherence scores were calculated for participants within each dietary pattern, with higher scores indicating higher adherence. Mixed models were used to examine the effect of each dietary pattern on changes in QOL at 6- and 12-month follow-ups, controlling for cancer stage, biological sex, body mass index (BMI), smoking status, and age. Results: Participants (N = 174) were, on average, 56 ± 14 years old and were mostly female (51.5%), stage III or IV (51.7%), never smokers (60.2%), non-Hispanic (97.1%), and White (83.3%) with a BMI of 27.9 ± 6.1 kg/m². PCA revealed two emerging dietary patterns: “Western diet”, characterized by processed meats, refined grains, and sugars, and “Prudent diet” characterized by lean proteins, fruits, and vegetables. Higher adherence to a Western diet was associated with worse social functioning at 6-month follow-up (FE = −12.6, p = 0.010). Loss of appetite from 6 to 12 months was associated with higher adherence to both the Western and Prudent dietary patterns (FE = 1.5, p = 0.044; FE = 1.3, p = 0.046, respectively). Neither dietary pattern was associated with global QOL score at 6- or 12-month follow-up (p’s > 0.05). Conclusions: Among CRC survivors in the United States, the Western diet was concurrently associated with worse social functioning. Loss of appetite was reported by CRC survivors following both dietary patterns, suggesting that loss of appetite may be a global experience for CRC survivors during this timeframe. Further research is needed to understand specific social challenges experienced by CRC survivors and develop supportive care interventions to address appetite and nutritional concerns. Full article

Background and Objectives: The burdened symptomatology accompanying advanced non-small-cell lung cancer (NSCLC) is associated with poor prognosis and lower quality of life (QoL). Although both chemotherapy and immunotherapy increase survival, they are still associated with reduced functionality due to their toxicity. This study aimed to estimate the QoL and symptom burden of NSCLC patients receiving second-line chemotherapy compared to patients receiving second-line immunotherapy. Materials and Methods: This comparative, prospective study, conducted from January 2020 to December 2021, included 111 NSCLC patients who were divided into two groups: 61 patients receiving second-line chemotherapy and 50 patients receiving second-line immunotherapy. Patients’ QoL and symptom burden were estimated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C-30) (value range 0–100) from treatment cycle 1 to 6. Results: The QoL (mean score > 50) and functionality dimensions (mean score > 50) were moderate to good in both treatment groups, while the symptom burden did not appear to be a serious problem (mean score < 50). From cycle 3 to cycle 5, QoL was significantly better in the immunotherapy group. From cycle 3, the role and social functioning scores were higher in the immunotherapy group, while emotional and cognitive functioning were higher from cycle 2 (p <0.05). The chemotherapy group experienced higher levels of nausea/vomiting, constipation and financial difficulties in all the cycles (p < 0.05). Fatigue and appetite loss were significantly greater from cycle 2 and insomnia was significantly greater from cycle 3. On the contrary, the immunotherapy group experienced higher levels of diarrhea in cycles 5 and 6 (p < 0.05). Conclusions: Although both therapy groups did not report significantly impaired QoL and severe symptoms, it seems that QoL improved in the immunotherapy group, which reported a lower symptom burden compared to the chemotherapy group. Full article

Background: Lung cancer carries a high burden of systemic symptoms, including in survivors, leading to a reduced quality of life (QoL). We assessed whether a 12-week multicomponent supervised exercise programme, including muscular strength and aerobic training, was beneficial in patients who had undergone surgery for early non-small cell lung cancer (NSCLC) in terms of physical performance, QoL, and metabolic and nutritional analytical parameters. Methods: Physical performance was measured by gait speed, handgrip strength, 30 s sit-to-stand (30s-STS) test repetitions, distance covered in the 6 min walk test (6MWT), and the Short Physical Performance Battery (SPPB) score. QoL was assessed with the EORTC-QLQ-C30 questionnaire. Blood glucose, cholesterol, triglycerides, total proteins, albumin, pre-albumin, creatinine, c-reactive protein, insulin-growth factor 1 (IGF-1), and the haemoglobin and hematocrit percentages were measured before and after the intervention in order to observe any beneficial effects related to metabolic markers. Results: After the intervention, the mean scores for the 6MWT (p < 0.001), STS (p < 0.001), 6MWT (p < 0.01), and SPPB (p < 0.01) had significantly improved. However, handgrip strength and nutritional analytical were unchanged. The EORTC-QLQ-C30 functions and symptoms significantly improved after the intervention (p < 0.05 and p < 0.01, respectively). A significant decrease in cholesterol, triglycerides, and IGF-1 and a significant increase in pre-albumin in blood was also observed post-intervention (p < 0.05). Conclusions: This supervised, community-based 12-week multicomponent was feasible (adherence rate 70.35%) and provided benefits not only to physical performance but also to the quality of life of patients with NSCLC. Full article

Background: Due to their high toxicity, cancer treatments produce multiple sequelae, including fatigue, which has a great impact on quality of life. Therefore, the aim of this study is to evaluate the efficacy on quality of life, fatigue, and functional capacity of a short-term exercise program combining aerobic exercise, resistance training, and stretching for 6 weeks in cancer patients. Methods: The design of the study was quasi-experimental, which included a group of 30 women who were receiving or had received in the last year chemotherapy, radiotherapy, or hormonal treatment. The exercise supervised program with vigorous intensity lasted for six weeks and consisted of three distinct blocks: aerobic exercise (25 min), resistance training (20 min), and stretching exercises (15 min). Before and after starting the exercise program quality of life (EORTC QLQ-C30 questionnaire), functional capacity [6 min Walking Test (6MWT), Handgrip Test (HGT), 30-Second Sit-to-Stand Test (30s-STST)], and fatigue (FACIT-F questionnaire) were measured. Results: In the EORTC QLQ-C30 questionnaire significantly higher scores were observed in the global health status scale (p < 0.05), as well as in the functional scale in the role functioning, emotional functioning, and cognitive functioning items (p < 0.05), indicating a higher quality of life and overall health level. There was also a reduction in fatigue (p < 0.05), obtaining higher scores on the FACIT-F questionnaire after the exercise program. Additionally significant improvements are observed in 6MWT, HGT, and 30s-STST following the implementation of the exercise program (p < 0.05). Conclusions: A 6-week exercise protocol, with a vigorous intensity, including resistance training, endurance, and stretching exercises can produce significant improvements in quality of life and reduction in fatigue, as well as improve muscle strength and functional capacity. Full article

Physical activity improves breast cancer-related symptoms in women and decreases cancer-related mortality. The main objective of this systematic review is to synthesize and analyze the evidence of the effect of dragon boating on the quality of life of female breast cancer survivors. A systematic review based on the PRISMA method was conducted using four databases (Web of Science, Scopus, Cochrane and Pubmed). The search phrase used was “Breast Cancer” AND “Dragon Boat” AND “Quality of Life”. The search was conducted in June 2024. The PEDro method was used to ensure the quality of the publications. A total of 77 articles published until 2024 were selected, of which 10 met the inclusion criteria of assessing the application of dragon boating and that used a validated instrument to assess quality of life. There is no homogeneity in terms of the instrument used to measure QOL. The SF-36 was the most commonly used, followed by the FACT-B and the EORTC QLQ-C30. Five out of ten articles compared the improvement in quality of life between dragon boating and other physical activities, while 6 out of 10 analyzed the pre–post effect of dragon boat use. Dragon boating is a physical activity alternative that improves the quality of life of breast cancer survivors and reduces the symptomatology caused by the disease and its treatments. As dragon boat programs are applied over a longer period of time, the improvements in quality of life are greater. When compared with other types of physical activity, dragon boating does not show significant differences that position it as a better option for this population. Full article

The EuroQoL 5-Dimension 5-Level questionnaire (EQ-5D-5L) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) are commonly used Patient-Reported Outcome Measures (PROMs) for breast cancer. This study assesses and compares the internal responsiveness of the EQ-5D-5L and EORTC QLQ-C30 in Dutch breast cancer patients during the first year post-surgery. Women diagnosed with breast cancer who completed the EQ-5D-5L and EORTC QLQ-C30 pre-operatively (T0), 6 months (T6), and 12 months post-surgery (T12) were included. Mean differences of the EQ-5D-5L and EORTC QLQ-C30 between baseline and 6 months (delta 1) and between baseline and 12 months post-surgery (delta 2) were calculated and compared against the respective minimal clinically important differences (MCIDs) of 0.08 and 5. Internal responsiveness was assessed using effect sizes (ES) and standardized response means (SRM) for both deltas. In total, 333 breast cancer patients were included. Delta 1 and delta 2 for the EQ-5D-5L index and most scales of the EORTC QLQ-C30 were below the MCID. The internal responsiveness for both PROMs was small (ES and SRM < 0.5), with greater internal responsiveness for delta 1 compared to delta 2. The EQ-5D-5L index showed greater internal responsiveness than the EORTC QLQ-C30 Global Quality of Life scale and summary score. These findings are valuable for the interpretation of both PROMs in Dutch breast cancer research and clinical care. Full article

Purpose: The purpose of this study is to study the evolution of quality of life (QoL) in the first 5 years following Intensity-modulated radiation therapy (IMRT) for prostate cancer (PCa) and to determine possible associations with clinical/treatment data. Material and methods: Patients were enrolled in a prospective multicentre observational trial in 2010-2014 and treated with conventional (74–80 Gy, 1.8–2 Gy/fr) or moderately hypofractionated IMRT (65–75.2 Gy, 2.2–2.7 Gy/fr). QoL was evaluated by means of EORTC QLQ-C30 at baseline, at radiation therapy (RT) end, and every 6 months up to 5 years after IMRT end. Fourteen QoL dimensions were investigated separately. The longitudinal evaluation of QoL was analysed by means of Analysis of variances (ANOVA) for multiple measures. Results: A total of 391 patients with complete sets of questionnaires across 5 years were available. The longitudinal analysis showed a trend toward the significant worsening of QoL at RT end for global health, physical and role functioning, fatigue, appetite loss, diarrhoea, and pain. QoL worsening was recovered within 6 months from RT end, with the only exception being physical functioning. Based on ANOVA, the most impaired time point was RT end. QoL dimension analysis at this time indicated that acute Grade ≥ 2 gastrointestinal (GI) toxicity significantly impacted global health, physical and role functioning, fatigue, appetite loss, diarrhoea, and pain. Acute Grade ≥ 2 genitourinary (GU) toxicity resulted in lower role functioning and higher pain. Prophylactic lymph-nodal irradiation (WPRT) resulted in significantly lower QoL for global health, fatigue, appetite loss, and diarrhoea; lower pain with the use of neoadjuvant/concomitant hormonal therapy; and lower fatigue with the use of an anti-androgen. Conclusions: In this prospective, longitudinal, observational study, high radiation IMRT doses delivered for PCa led to a temporary worsening of QoL, which tended to be completely resolved at six months. Such transient worsening was mostly associated with acute GI/GU toxicity, WPRT, and higher prescription doses. Full article

Radical Cystectomy (RC) and Urinary Diversion (UD) is a complex surgery associated with a significant impact on health-related quality of life (HRQoL). However, HRQoL assessment is too often overlooked, with survival and complications being the most commonly investigated outcomes. This study aimed to identify the most impaired HRQoL features in patients receiving RC, compared to a healthy population (HP) control, as well as patients’ recovery after surgery, differentiating between patients receiving ORC and RARC. Patients with Bca, who were candidates for RC with curative intent, were enrolled in the “BCa cohort”. HRQoL outcomes were collected with an EORTC QLQ-C30 questionnaire. These were collected at baseline, and then at 6-, 12- and 24 mo after surgery in the BCa cohorts, and at baseline in the HP cohort. A 1:1 propensity score matched (PSM)-analysis, adjusted for age, Charlson Comorbidity Index (CCI) and smoking history, was performed. Between January 2018 and February 2023, a total of 418 patients were enrolled in the study, 116 and 302 in the BCa and HP cohorts, respectively. After applying the 1:1 propensity scored match (PSM) analysis, two homogeneous cohorts were selected, including 85 patients in each group. Baseline HRQoL assessment showed a significant impairment in terms of emotional and cognitive functioning, appetite loss and financial difficulties for the BCa cohort. Among secondary outcomes, we investigated patients’ recovery after RC and UD, comparing HRQoL outcome questionnaires between the HP and BCa cohorts at 6-, 12- and 24 mo after surgery, and a subgroup analysis was performed differentiating between patients receiving ORC and RARC with totally intracorporeal UD. Interestingly, ORC compared to RARC provided a major impact on HRQoL recovery across the early, mid and long term. In particular, the ORC cohort experienced a major impairment in terms of symptoms scales items such as fatigue, nausea and vomiting, pain and appetite loss. Consequently, comparing ORC and RARC vs. HP reported a major HRQoL impairment in the ORC cohort, possibly defining a benefit of RARC in early, mid- and long-term recovery. To conclude, this study confirmed the undeniable impact of RC on HRQoL. Interestingly, we highlighted the benefit of RARC in early, mid- and long-term recovery, expressed as less impairment of symptoms scales. Full article

Background: Chronic cancer-related fatigue is difficult to manage in breast cancer survivors. The tango trial showed that a six-week tango Argentino program was effective in reducing fatigue and improving quality of life, and here we investigated the sustainability of this tango program for breast cancer survivors. Methods: Stage I–III breast cancer survivors with increased fatigue symptoms were analyzed. The fifty participants in the tango trial were compared with a control cohort (n = 108) who did not participate in the tango program. Using the European Organization for Research and Treatment of Cancer Questionnaire C30 (EORTC-QLQ-C30) and the German version of the cancer fatigue scale (CFS-D) self-reported quality of life parameters were assessed and longitudinal changes, correlations, and association factors were calculated. Results: Significant improvements in fatigue (p = 0.006), physical functioning (p = 0.01), and diarrhea (p = 0.04) persisted in the 50 Tango participants at 6 months, but not in the control cohort. Twelve months after joining the tango program, increased fatigue was associated with reduced sporting activities (p = 0.0005), but this was not the case for tango dancing. Conclusions: The present results suggest that tango may be appropriate as a component of early supportive and follow-up care programs, to promote health-related quality of life and physical activity and also eventually to improve long-term clinical outcomes of breast cancer survivors. Trial registration: Trial registration numbers DRKS00013335 on 27 November 2017 and DRKS00021601 on 21 August 2020 retrospectively registered. Full article