Background:
The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events is an item library designed for eliciting patient-reported adverse events in oncology. For each ...adverse event, up to three individual items are scored for frequency, severity, and interference with daily activities. To align the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events with other standardized tools for adverse event assessment including the Common Terminology Criteria for Adverse Events, an algorithm for mapping individual items for any given adverse event to a single composite numerical grade was developed and tested.
Methods:
A five-step process was used: (1) All 179 possible Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events score combinations were presented to 20 clinical investigators to subjectively map combinations to single numerical grades ranging from 0 to 3. (2) Combinations with <75% agreement were presented to investigator committees at a National Clinical Trials Network cooperative group meeting to gain majority consensus via anonymous voting. (3) The resulting algorithm was refined via graphical and tabular approaches to assure directional consistency. (4) Validity, reliability, and sensitivity were assessed in a national study dataset. (5) Accuracy for delineating adverse events between study arms was measured in two Phase III clinical trials (NCT02066181 and NCT01522443).
Results:
In Step 1, 12/179 score combinations had <75% initial agreement. In Step 2, majority consensus was reached for all combinations. In Step 3, five grades were adjusted to assure directional consistency. In Steps 4 and 5, composite grades performed well and comparably to individual item scores on validity, reliability, sensitivity, and between-arm delineation.
Conclusion:
A composite grading algorithm has been developed and yields single numerical grades for adverse events assessed via the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events, and can be useful in analyses and reporting.
Ripretinib is a novel switch-control kinase inhibitor that inhibits KIT and PDGFRA signaling. In the INVICTUS phase 3 trial, ripretinib increased median progression-free survival and prolonged ...overall survival vs. placebo in ≥ fourth-line advanced GIST. Here, we report prespecified analysis of quality of life (QoL) as assessed by patient-reported outcome (PRO) measures and an exploratory analysis evaluating the impact of alopecia on QoL.
In the INVICTUS trial (NCT03353753), QoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30; physical function, role function, overall health, and overall QoL) and the EuroQoL 5-Dimension 5-Level (EQ-5D-5 L; visual analogue scale). Analysis of covariance (ANCOVA) models compared changes in scores from baseline to treatment cycle 2, day 1 within and between ripretinib and placebo. Within the ripretinib arm, repeated measures models assessed the impact of alopecia on QoL.
Patients receiving ripretinib maintained QoL (as assessed by the EORTC QLQ-C30 and EQ-5D-5 L PRO measures) from baseline to cycle 2, day 1 whereas QoL declined with placebo, resulting in clinically significant differences between treatments (nominal P < 0.01). The most common treatment-emergent adverse event with ripretinib was alopecia; however, QoL was similarly maintained out to treatment cycle 10, day 1 in patients receiving ripretinib who developed alopecia and those who did not.
PRO assessments in the INVICTUS trial suggest that patients on ripretinib maintain their QoL out to C2D1, unlike patients receiving placebo. Longitudinal QoL was maintained for patients receiving ripretinib out to cycle 10, day 1 (approximately 8 months; past the point of median progression-free survival with ripretinib 6.3 months), even if the patients developed alopecia.
ClinicalTrials.gov Identifier: NCT03353753 ; first posted: November 27, 2017.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The asymmetric hydroxylation and fluorination catalyst Ru(OEt
(PNNP)
(PNNP = chiral tetradentate ligand with a P
donor set) reacts with 1,3-dicarbonyl compounds to give dicationic adducts and, upon ...deprotonation, the corresponding enolato complexes. The relevance of these species to catalytic O- and F-transfer is investigated.
Technical advancements of the past decade have led to massive improvements regarding imaging and visualization in trauma care. Digital imaging technology has fundamentally changed most processes in ...fracture management. However, the digital revolution in trauma surgery has just begun.
Optical tracking navigation is currently the gold standard for positioning of implants for advanced applications in trauma surgery. Digital technology may enable the surgeon to achieve the same level of safety even in non-navigated placement of screws: We developed a new planning tool to transcript a preoperative into a semi-transparent “fluoroscopic like” image that can be identified intraoperatively and used as a map for the safe placement of sacro-iliac screws based on the “vestibule concept”. In the future, development of artificial intelligence algorithms may provide features like automated segmentation of bone-fragments and other applications for a systematic fracture analysis to improve the standard of care in trauma surgery.
Digital transformation has massive impact on diagnostics and surgical management of pelvic fractures. Improved visualization technology provides a better understanding of the surgical anatomy of the pelvis and may enable the surgeon to achieve greatest safety in percutaneous placement of screws even without using optical tracking navigation tools. The “para-axial fusion technique” is a useful tool to plan fluoroscopic views based on a 3D dataset prior to the surgery.
We compared the absorption of eicosapentaenoic (EPA, 20:5n−3), docosahexaenoic (DHA, 22:6n−3), and decanoic acids in mesenteric lymph duct-cannulated rats following intragastric administration of two ...oils with different intramolecular triacylglycerol structures. One oil had a specific triacylglycerol structure with EPA and DHA located in the sn-2 position and decanoic acid in the sn-1 and sn−3 positions (specific M-n3-M) whereas the other oil had a random fatty acid distribution (random M-n3-M). The mol% (mol/100 mol total fatty acids) of fatty acids in the two oils was similar, with ≈66 mol% of decanoic acid and 22 mol% of EPA and DHA. The lymphatic transport (µg/min) of EPA and DHA as well as the mol% in the total lymph lipids were significantly (both P < 0.01) increased following intragastric administration of specific M-n3-M compared with random M-n3-M. The mol% of decanoic acid in the total lymph lipids was significantly (P < 0.01) higher after random M-n3-M compared with specific M-n3-M but the transport (µg/min) of decanoic acid was not significantly different. We conclude that under our experimental conditions specific M-n3-M with EPA and DHA predominantly in the sn-2 position of the triacylglycerols was a more readily absorbed source of EPA and DHA and in this context should be investigated further for the potential use in clinical nutrition.
The NAPOLI-1 study (NCT01494506) reported that liposomal irinotecan plus 5-fluorouracil and leucovorin (nal-IRI+5-FU/LV) improved overall survival vs 5-FU/LV with manageable toxicity in patients with ...metastatic pancreatic adenocarcinoma previously treated with gemcitabine-based therapy. Yet, clinicians need treatment strategies that also maintain the patient's health-related quality of life (HRQOL). Here, we report the HRQOL data.
Patients completed the European Organisation for Research and Treatment of Cancer QOL core questionnaire C30 (EORTC QLQ-C30) at baseline, every 6 weeks, and at 30 days after discontinuation of study treatment. Patient-reported outcomes (PROs) were scored according to EORTC guidelines. nal-IRI+5-FU/LV HRQOL was compared with 5-FU/LV. The PRO population comprised intent-to-treat patients who completed baseline and at least one subsequent assessment on the EORTC QLQ-C30. Data were also analysed for missingness.
Of 236 patients in the intent-to-treat population, 128 (54.2%) comprised the PRO population (71 in the nal-IRI+5-FU/LV arm; 57 the in 5-FU/LV arm). Of the remaining 108 patients (45.8%) not included in the PRO population, most progressed rapidly, making participation difficult. Median change from baseline was ≤10 points at weeks 6 and 12 in global health status or functional and symptom scale scores, except for fatigue, which deteriorated by 11.1 points with nal-IRI+5-FU/LV but did not change vs 5-FU/LV. The proportion of patients whose HRQOL improved or deteriorated was not significantly different between the arms.
In the NAPOLI-1 study, HRQOL was maintained with nal-IRI+5-FU/LV in patients with metastatic pancreatic adenocarcinoma previously treated with a gemcitabine-based regimen, while survival was significantly extended.
•Pancreatic cancer and chemotherapy can have a detrimental impact on health-related quality of life (HRQOL).•HRQOL was assessed in metastatic pancreatic ductal adenocarcinoma that had progressed on prior gemcitabine-based therapy.•In the NAPOLI-1 study, patients received liposomal irinotecan plus 5-flurouracil/leucovorin (nal-IRI+5-FU/LV) or 5-FU/LV.•HRQOL was maintained over time for nal-IRI+5-FU/LV vs 5-FU/LV alone.•Maintained patient HRQOL and survival benefit were seen with nal-IRI+5-FU/LV vs 5‑FU/LV alone in this global phase 3 study.
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Background: Ripretinib (R) is a switch-control tyrosine kinase inhibitor (TKI) indicated for the treatment of patients (pts) with advanced gastrointestinal stromal tumor (GIST) after prior ...treatment with ≥3 TKIs. In the INTRIGUE study (NCT03673501) there was no significant difference in median PFS (primary endpoint) between R and sunitinib (S). We present exploratory analyses of tolerability data and selected pt reported outcomes (PROs). Methods: Pts were randomized 1:1 to R 150 mg QD or S 50 mg QD 4 weeks on/2 weeks off.Dose modification was allowed for toxicity management. The event of interest was severe or life-threatening (grade ≥3) treatment-related adverse event prior to progression (sTRAE). Days with at least one sTRAE were summed for all treated pts and for pts with ≥1 sTRAE event. PROs were assessed using questions from EORTC QLQ-C30 and Dermatology Life Quality Index (DLQI) at cycle 1 (C1) day 1 (D1), D15, and D29; D1 and D29 of all other cycles; as well as at end of treatment. Differences in PRO scores between baseline and later assessments were calculated across visits. Long-term data will be presented. Results: Pts receiving R (n = 223) versus (vs) S (n = 221) experienced fewer sTRAEs (24% vs 51%, respectively). For all treated pts, the mean time with sTRAEs was 11 days for R and 42 days for S (ratio 0.27, P<0.0001). For pts with ≥1 sTRAE, the mean number of days with a sTRAE was 48 days for R vs 81 days for S (ratio 0.59, p = 0.037). Completion of PRO assessments across the two treatment arms was similar (baseline: R n = 199, S n = 199; C1 D29: R n = 167, S n = 177). Significant differences in self-reported functioning and symptoms were observed by C1 D29. For PROs relating to commonly reported sTRAEs, except constipation, pts in the R arm reported better outcomes than pts in the S arm. Pts in the R arm reported significantly (p<0.05) less decline compared to baseline in pt-reported role function as well as less increase, or improvement, in symptoms of fatigue, appetite loss, diarrhea, nausea/vomiting, and pain vs pts in the S arm. Moderate or severe effect of skin toxicity on pt life, as measured by DLQI in the R arm (n = 165) and in the S arm (n = 175), was observed in 6.6% of pts in the R arm vs 14.8% of pts in the S arm (p = 0.015). Conclusions: In the INTRIGUE study the total number of days with sTRAEs was fewer for pts receiving R vs S. Pts in the R arm also reported significantly less decline in pt-reported role function and less increase in symptoms related to commonly reported sTRAEs, except constipation, vs pts in the S arm. Medical writing provided by Costello Medical. Clinical trial information: NCT03673501.
In the INTRIGUE trial, ripretinib showed no significant difference versus sunitinib in progression-free survival for patients with advanced gastrointestinal stromal tumour (GIST) previously treated ...with imatinib. We compared the impact of these treatments on health-related quality of life (HRQoL).
Patients were randomised 1:1 to once-daily ripretinib 150 mg or once-daily sunitinib 50 mg (4 weeks on/2 weeks off). Patient-reported outcomes were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer-30 (EORTC QLQ-C30) questionnaire at day (D)1, and D29 of all cycles until treatment discontinuation. Change from baseline was calculated. Time without symptoms or toxicity (TWiST) was estimated as the mean number of days without progression, death, or grade ≥3 treatment-emergent adverse events per patient over 1 year of follow-up.
Questionnaire completion at baseline was 88.1% (199/226) for ripretinib and 87.7% (199/227) for sunitinib and remained high for enrolled patients throughout treatment. Patients receiving sunitinib demonstrated within-cycle variation in self-reported HRQoL, corresponding to the on/off dosing regimen. Patients receiving ripretinib reported better HRQoL at D29 assessments than patients receiving sunitinib on all scales except constipation. HRQoL was similar between treatments at D1 assessments, following 2 weeks without treatment for sunitinib patients. TWiST was greater for ripretinib patients (173 versus 126 days).
Patients receiving ripretinib experienced better HRQoL than patients receiving sunitinib during the dosing period and similar HRQoL to patients who had not received sunitinib for 2 weeks for all QLQ-C30 domains except constipation. Ripretinib may provide clinically meaningful benefit to patients with advanced GIST previously treated with imatinib.
•Health-related quality of life was evaluated in the INTRIGUE (NCT03673501) study.•Patients with advanced GIST received ripretinib or sunitinib.•Patients taking ripretinib generally reported less reduction in quality of life.•Patients taking ripretinib reported more time without treatment toxicity.•Ripretinib may provide clinically meaningful benefit to patients with advanced GIST.
Impact of the COVID 19 Pandemic on Radiological Imaging in Germany Schmidbauer, Martina; Grenacher, Lars; Juchems, Markus S. ...
RöFo : Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebende Verfahren,
06/2022, Letnik:
194, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Abstract
Purpose
To analyze the impact of the COVID-19 pandemic in 2020 on the radiological imaging volume in Germany.
Materials und Methods
In this retrospective multicenter study, we analyzed CT ...and MRI examinations of 7 radiology institutes across Germany from January to December 2020. The imaging volume was compared to 2019 (Wilcoxon-Mann-Whitney test). Modality, patient service locations, and examined body parts were assessed in consideration of time periods of the pandemic. In addition, correlation with the incidence of SARS-CoV-2 cases and associated death was performed (Spearman-test).
Results
In total, in 2020, imaging volume declined by 4 % (n = 8314) compared with 2019 (p < 0.05). The hard lockdown during the first pandemic wave (calendar week 12–16, March 22 – April 19) revealed the highest decrease with 29 % (n = 894, p < 0.01), with the greatest decrease in CT (36 % vs. MRI 26 %), outpatients (38 %, p < 0.01), and imaging of the spine and extremities (51–72 %, < 0.05 – p < 0.01). Examinations referred from the emergency department (–13 %, p < 0.05) and CT of the chest (–16 %, p < 0.05) were least affected. With the end of the first wave, gradual normalization of the imaging volume was observed and persisted until the end of the observation period. A reduction of imaging volume negatively correlated with the incidence of SARS-CoV-2-positive cases and associated deaths (r = 0.28 and 0.49, p < 0.05 and p < 0.001).
Conclusion
The COVID-19 pandemic was associated with a significant temporary decline in imaging volume. After the first lockdown period, a quick recovery was observed with radiologic imaging examinations steadily approaching prior-year figures.
Key points:
This study assesses the impact of dynamic pandemic activity on radiological imaging in a multicenter analysis in Germany.
The COVID-19 pandemic was associated with a temporary decline in CT and MRI scans.
Relaxation of restrictions was associated with fast normalization of imaging volumes to prior-year levels, which persisted until the end of the year.
Significant catch-up effects were not observed.
Citation Format
Schmidbauer M, Grenacher L, Juchems MS et al. Impact of the COVID 19 Pandemic on Radiological Imaging in Germany. Fortschr Röntgenstr 2022; 194: 625 – 633
Zusammenfassung
Ziel
Untersuchung der Auswirkungen der COVID-19-Pandemie auf die Durchführung radiologischer Bildgebung in Deutschland.
Material und Methoden
In dieser retrospektiven multizentrischen Studie wurden die durchgeführten CT- und MRT-Bildgebungen 7 deutschlandweiter radiologischer Zentren von Januar bis Dezember 2020 analysiert. Das Untersuchungsvolumen wurde mit dem Vorjahreszeitraum verglichen (Wilcoxon-Mann-Whitney-Test). Die Auswertung der aggregierten Daten erfolgte differenziert nach Modalität, Zuweiser, Körperregion und unter besonderer Berücksichtigung der zeitlichen Pandemieentwicklung. Die Untersuchungszahlen wurden zudem mit der Inzidenz von SARS-CoV-2-positiven Fällen und assoziierten Todesfällen korreliert (Spearman-Test).
Ergebnisse
Im Pandemiejahr 2020 wurden insg. 4 % (n = 8314) weniger CT- und MRT-Untersuchungen durchgeführt als im Vorjahr (p < 0,05). Die Differenz ist vornehmlich auf den Zeitraum des harten Lockdowns (Kalenderwoche 12–16, 22. März bis 19. April 2020) zurückzuführen, welcher im Vergleich zum Vorjahreszeitraum zu einem Rückgang der Untersuchungen um 29 % geführt hat (n = 894, p < 0,01). MRT-Untersuchungen waren dabei stärker betroffen als CT-Untersuchungen (36 % vs. 26 %). Der größte Rückgang war mit –38 % (p < 0,01) bei ambulanten Patienten zu verzeichnen und bei Untersuchungen von Wirbelsäule und Extremitäten (–51 % bis –72 %, p < 0,05 bis p < 0,01). Am geringsten tangiert waren Untersuchungen aus den Zentralen Notaufnahmen (–13 %, p < 0,05) sowie CT-Untersuchungen des Thorax (–16 %, p < 0,05). Das Ende des harten Lockdowns ging mit einer sukzessiven Normalisierung des Untersuchungsvolumens auf das Vorjahresniveau einher, die auch mit Beginn der zweiten Pandemiewelle und des milderen Lockdowns am Jahresende anhielt. Der Rückgang der Untersuchungen 2020 korrelierte dabei negativ mit der Inzidenz an SARS-CoV-2-positiven Fällen und assoziierten Todesfällen (r = 0,28 und 0,49; p < 0,05 und p < 0,001).
Schlussfolgerung
Die COVID-19-Pandemie in Deutschland führte 2020 temporär zu einem signifikanten Rückgang radiologischer CT- und MRT-Untersuchungen. Nach Ende des ersten Lockdowns im Frühjahr zeigte sich eine rasche Erholung der Untersuchungszahlen mit weitgehender Stabilisierung des Untersuchungsvolumens auf das Vorjahresniveau.
Kernaussagen:
Die Studie zeigt die pandemiebedingten Veränderungen radiologischer Bildgebung in einer multizentrischen, deutschlandweiten Analyse.
Im Jahr 2020 kam es während des ersten Lockdowns zu einem temporären quantitativen Rückgang an CT- und MRT-Untersuchungen.
Mit Beginn der ersten Lockerungen trat eine zügige Normalisierung der Untersuchungsvolumina auf Vorjahresniveau ein, die bis zum Jahresende anhielt.
Signifikante Nachholeffekte wurden nicht beobachtet.
Zitierweise
Schmidbauer M, Grenacher L, Juchems MS et al. Impact of the COVID 19 Pandemic on Radiological Imaging in Germany. Fortschr Röntgenstr 2022; 194: 625 – 633
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