Diese Pilotstudie findet vorbereitend für das AdThera-Projekt (Adhärenz von Therapieempfehlungen aus multidisziplinären Tumorkonferenzen in der Onkologie) statt. Dieses soll die Umsetzung der Therapieempfehlungen der multidisziplinären Tumorkonferenzen (MTK) des Pius-Hospitals Oldenburg in verschiedenen weiterversorgenden Versorgungsorganisationen beurteilen, Gründe für partielle Adhärenz/ Non-Adhärenz in deren Umsetzung finden, sowie einen eventuellen Zusammenhang zwischen dem Grad der Adhärenz und dem Überleben der Patient:innen erörtern. Die vorliegende Pilotstudie ist dem AdThera-Projekt vorgeschaltet. Primäres Ziel ist die Entwicklung einer geeigneten Methodik zur Durchführung des Projekts und Erstellung der zur Beantwortung der Forschungsfragen benötigten Dateninfrastruktur. Zur Sicherstellung der Funktionsfähigkeit dieser Infrastruktur wird ein Probelauf, dessen Ergebnisse Vorabergebnisse des AdThera-Projekts darstellen, mit reduzierter Fallzahl durchgeführt. Methoden: Hierfür wurden entitätsspezifische Datenbanken und eine entitätsübergreifende Auswertungsmatrix auf Basis der im Erhebungszeitraum 2014 bis 2018 gültigen Onkopedia-Leitlinien für die fünf Tumorentitäten Lungen-, Brust-, Darm-, Magen- und Pankreaskrebs erstellt. Anschließend erfolgte eine Evaluation der Datenbanken durch Aufbereitung und Auswertung von Sekundärdaten aus Primärfällen der Organkrebszentren des Pius-Hospitals. Ergebnisse: Es ließen sich alle für die angestrebten Auswertungen des AdThera-Projekts benötigten Variablen generieren. Die Vollständigkeit dieser Daten schwankte bei der Durchführung des Probelaufs von Fall zu Fall. Von den insgesamt 349 Fälle erhobenen Fällen erfüllten 318 Fälle (91,1%) die Einschlusskriterien. In diesen Fällen konnte die Adhärenz in 93,1% der Fälle (296 von 318 Fälle) ermittelt werden. Eine vollständige Adhärenz zu den MTK-Therapieempfehlungen lag im Pius-Hospital in 87,1%, in der Onkologischen Praxis Oldenburg 87,0% und in externen Versorgungseinrichtungen 100% der Fälle vor. Häufigster Grund für eine nicht-adhärente Umsetzung der MTK-Therapieempfehlungen war der Tod vor/direkt nach Start der Therapie mit 43,8%, gefolgt vom Patient:innenwunsch mit 37,5% und den Patient:innenmerkmalen mit 34,4%. Weitere Gründe waren selten. Das mediane Überleben von Patient:innen, deren MTK-Therapieempfehlung vollständig adhärent umgesetzt wurde, zeigte sich in dieser Studie signifikant länger als das Überleben von Patient:innen, deren MTK-Therapieempfehlung non-adhärent umgesetzt wurde. Fazit: Die Funktionsfähigkeit der erstellten Dateninfrastruktur konnte nachgewiesen werden. Im Rahmen der Evaluation der Infrastruktur konnten erste Ergebnisse des AdThera-Projekts präsentiert und Schlussfolgerungen für das AdThera-Projekt gezogen werden.
Objective: This pilot study is preparatory to the AdThera project (Adherence to Therapy Recommendations from Multidisciplinary Tumor Conferences in Oncology). The aim of this pilot study is to assess the implementation of the therapy recommendations of the multidisciplinary tumor conferences (MTC) of the Pius-Hospital Oldenburg in different care organizations, to find reasons for partial adherence/non-adherence in their implementation, and to discuss a possible correlation between the degree of adherence and the survival of the patients. The present pilot study precedes the AdThera project. The primary goal is to develop a suitable methodology for the implementation of the project and to create the data infrastructure needed to answer the research questions. To ensure the viability of this infrastructure, a trial run, the results of which represent preliminary findings of the AdThera project, will be conducted with a reduced number of cases. Methods: For this purpose, entity-specific databases and a cross-entity evaluation matrix were created based on the Onkopedia guidelines for the five tumor entities lung, breast, colorectal, gastric, and pancreatic cancer that were valid during the 2014 to 2018 data collection period. Subsequently, an evaluation of the databases was performed by processing and analyzing secondary data from primary cases at the Pius Hospital Cancer Centers. Results: All variables needed for the intended evaluations of the AdThera project could be generated. The completeness of these data varied from case to case during the trial run. Of the total 349 cases collected, 318 cases (91.1%) met the inclusion criteria. Among these cases, adherence was determined in 93.1% of cases (296 of 318 cases). Complete adherence to MTK therapy recommendations was present in 87.1% of cases at Pius Hospital, 87.0% at the Oldenburg Oncology Practice, and 100% at external care facilities. The most frequent reason for non-adherence to the MTK therapy recommendations was death before/immediately after the start of therapy with 43.8%, followed by the patient:s wish with 37.5% and the patient:s characteristics with 34.4%. Other reasons were rare. The median survival of patients whose MTK therapy recommendation was implemented fully adherently was shown to be significantly longer than the survival of patients whose MTK therapy recommendation was implemented non-adherently in this study. Conclusion: The functionality of the data infrastructure was demonstrated. During the evaluation of the infrastructure, first results of the AdThera project could be presented and conclusions for the AdThera project could be drawn.
Online verfügbar: 13. Dezember 2024, Artikelversion: 6. Mai 2024
Checkpoint inhibitor; NSCLC; Predictive biomarker
4207 Introduction - Programmed death-ligand 1 expression currently represents the only validated predictive biomarker for immune checkpoint inhibition in metastatic NSCLC in the clinical routine, but it has limited value in distinguishing responses. Assessment of KRAS and TP53 mutations (mut) as surrogate for an immunosupportive tumor microenvironment (TME) might help to close this gap. - Methods - A total of 696 consecutive patients with programmed death-ligand 1-high (≥50%), nonsquamous NSCLC, having received molecular testing within the German National Network Genomic Medicine Lung Cancer between 2017 and 2020, with Eastern Cooperative Oncology Group performance status less than or equal to 1 and pembrolizumab as first-line palliative treatment, were included into this retrospective cohort analysis. Treatment efficacy and outcome according to KRAS/TP53 status were correlated with TME composition and gene expression analysis of The Cancer Genome Atlas lung adenocarcinoma cohort. - Results - Proportion of KRASmut and TP53mut was 53% (G12C 25%, non-G12C 28%) and 51%, respectively. In KRASmut patients, TP53 comutations increased response rates (G12C: 69.7% versus 46.5% [TP53mut versus wild-type (wt)], p = 0.004; non-G12C: 55.4% versus 39.5%, p = 0.03), progression-free survival (G12C: hazard ratio [HR] = 0.59, p = 0.009, non-G12C: HR = 0.7, p = 0.047), and overall survival (G12C: HR = 0.72, p = 0.16, non-G12C: HR = 0.56, p = 0.002), whereas no differences were observed in KRASwt patients. After a median follow-up of 41 months, G12C/TP53mut patients experienced the longest progression-free survival and overall survival (33.7 and 65.3 mo), which correlated with high tumor-infiltrating lymphocyte densities in the TME and up-regulation of interferon gamma target genes. Proinflammatory pathways according to TP53 status (mut versus wt) were less enhanced and not different in non-G12C and KRASwt, respectively. - Conclusions - G12C/TP53 comutations identify a subset of patients with a very favorable long-term survival with immune checkpoint inhibitor monotherapy, mediated by highly active interferon gamma signaling in a proinflammatory TME.
Journal of thoracic oncology Amsterdam : Elsevier, 2006 19(2024), 5, Artikel-ID 5, Seite 803-817 Online-Ressource
Brustkrebs ist unter Frauen weiterhin sowohl in Niedersachsen als auch in ganz Deutschland die häufigste Krebserkrankung. Die Betreuung der Patientinnen und Patienten kann sowohl in zertifizierten Brustzentren als auch in externen onkologischen Einrichtungen erfolgen. Im Rahmen des zertifizierten Brustkrebszentrums des Pius Hospitals wurde für die in dieser Studie betrachteten Patientinnen in einer interdisziplinären Tumorkonferenz ein individueller Therapieplan erstellt, der die aktuellen Empfehlungen der fachspezifischen Leitlinie beachtet. Die vorliegende Arbeit untersucht die Adhärenz der Tumorboardempfehlungen sowie dessen Einfluss auf das Gesamtüberleben. Zusätzlich werden mögliche Einflussfaktoren auf das Überleben ausgewertet, um für zukünftige Therapiekonzepte bestmöglich auf die Lebensumstände der Patientinnen eingehen zu können. Die retrospektiv durchgeführte Studie überprüft die Einhaltung der in den interdisziplinären Tumorkonferenzen empfohlenen Therapiekonzepte von Mammakarzinompatientinnen im Pius Hospital Oldenburg im Zeitraum von Januar 2014 bis Dezember 2018. Eingeschlossen wurden 1122 Patientinnen, die primär im Pius Hospital Oldenburg operiert wurden. Die am Brustzentrum des Pius Hospital Oldenburg betreuten Patientinnen weisen in größerem Maße eine Einhaltung der Tumorkonferenzbeschlüsse und ein längeres Überleben im Vergleich zu extern betreuten Patientinnen auf. Zusätzlich haben die Parameter verheiratet/verpartnert, ein CCI ≤ 2, ein positiver Hormonrezeptorstatus, die UICC-Stadien 0-II, das Fehlen von Fernmetastasen, eine Weiterbehandlung am zertifizierten Brustzentrum sowie die vollständige Adhärenz einen signifikanten Einfluss auf das Überleben.
Breast cancer still is the most diagnosed cancer entity in Lower Saxony and all over Germany. Patients can be cared for in certified breast cancer centers as well as in external oncological institutions. Breast cancer patients of the certified breast cancer center at Pius Hospital have been given individual treatment plans, which have been developed by an interdisciplinary tumor conference. This paper examines adherence to tumor conference decisions and the impact on overall survival. Furthermore, possible impact factors on survival are evaluated to respond to living circumstances of the patients regarding future treatment plans. This paper is a retrospective study to survey the adherence of breast cancer patients to recommended treatment plans of interdisciplinary tumor conferences in the Pius Hospital Oldenburg from January 2014 to December 2018. 1122 patients, who had primary surgery at Pius Hospital Oldenburg, have been included. Patients being treated at breast center Pius Hospital Oldenburg show a higher adherence to tumor conference decisions and a longer survival compared to patients, who were cared for externally. Furthermore, being married/partnered, a CCI ≤ 2, a positive hormone receptor status, UICC stages 0-II, no metastases, further treatment at the certified breast cancer center, and complete adherence have significant impact on survival.
von Oliver Illini ; Felix Saalfeld ; Petros Christopoulos ; Michaël Duruisseaux ; Anders Vikström ; Nir Peled ; Ingel Demedts ; Elizabeth Dudnik ; Anna Eisert ; Sayed M. S. Hashemi ; Urska Janzic ; Waleed Kian ; Katja Mohorcic ; Saara Mohammed ; Maria Silvoniemi ; Sacha I. Rothschild ; Christian Schulz ; Claas Wesseler ; Alfredo Addeo ; Karin Armster ; Malinda Itchins ; Marija Ivanović ; Diego Kauffmann-Guerrero ; Jussi Koivunen ; Jonas Kuon ; Nick Pavlakis ; Berber Piet ; Martin Sebastian ; Janna-Lisa Velthaus-Rusik ; Luciano Wannesson ; Marcel Wiesweg ; Robert Wurm ; Corinna Albers-Leischner ; Daniela E. Aust ; Melanie Janning ; Hannah Fabikan ; Sylvia Herold ; Anna Klimova ; Sonja Loges ; Yana Sharapova ; Maret Schütz ; Christoph Weinlinger ; Arschang Valipour ; Tobias R. Overbeck ; Frank Griesinger ; Marko Jakopovic ; Maximilian Hochmair ; Martin Wermke
EGFR exon 20 (EGFR Ex20) insertion mutations in non-small cell lung cancer (NSCLC) are insensitive to traditional EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is the only approved TKI specifically designed to target EGFR Ex20. We performed an international, real-world safety and efficacy analysis on patients with EGFR Ex20-positive NSCLC enrolled in a mobocertinib early access program. We explored the mechanisms of resistance by analyzing postprogression biopsies, as well as cross-resistance to amivantamab. Data from 86 patients with a median age of 67 years and a median of two prior lines of treatment were analyzed. Treatment-related adverse events (TRAEs) occurred in 95% of patients. Grade ≥3 TRAEs were reported in 38% of patients and included diarrhea (22%) and rash (8%). In 17% of patients, therapy was permanently discontinued, and two patients died due to TRAEs. Women were seven times more likely to discontinue treatment than men. In the overall cohort, the objective response rate to mobocertinib was 34% (95% CI, 24-45). The response rate in treatment-naïve patients was 27% (95% CI, 8-58). The median progression-free and overall survival was 5 months (95% CI, 3.5-6.5) and 12 months (95% CI, 6.8-17.2), respectively. The intracranial response rate was limited (13%), and one-third of disease progression cases involved the brain. Mobocertinib also showed antitumor activity following EGFR Ex20-specific therapy and vice versa. Potential mechanisms of resistance to mobocertinib included amplifications in MET, PIK3CA, and NRAS. Mobocertinib demonstrated meaningful efficacy in a real-world setting but was associated with considerable gastrointestinal and cutaneous toxicity.
International journal of molecular sciences Basel : Molecular Diversity Preservation International, 2000 25(2024), 7, special issue vom: Apr., Artikel-ID 3992, Seite 1-19 Online-Ressource
von Jan Alexander Stratmann ; Friederike Cornelia Althoff ; Paula Doebel ; Jacqueline Rauh ; Arne Trummer ; Ali Nuri Hünerlitürkoglu ; Nikolaj Frost ; Hüsameddin Yildirim ; Petros Christopoulos ; Oswald Burkhard ; Christian Meyer zum Büschenfelde ; Aaron Becker von Rose ; Jürgen Alt ; Sven Aries ; Maximilian Webendörfer ; Stefan Kaldune ; Mark Uhlenbruch ; Guergana Tritchkova ; Cornelius Waller ; Achim Rittmeyer ; Petra Hoffknecht ; Jan Braess ; Hans-Georg Kopp ; Christian Grohé ; Monica Schäfer ; Christian Schumann ; Frank Griesinger ; Jonas Kuon ; Martin Sebastian ; Niels Reinmuth
Background - Sotorasib is a first-in-class KRAS p.G12C-inhibitor that has entered clinical trials in pretreated patients with non-small cell lung cancer (NSCLC) in 2018. First response rates were promising in the CodeBreaK trials. It remains unclear whether response to sotorasib and outcomes differ in a real-world setting when including patients underrepresented in clinical trials. - Methods - Patients with KRAS p.G12C-mutated advanced or metastatic NSCLC received sotorasib within the German multicenter sotorasib compassionate use program between 2020 to 2022. Data on efficacy, tolerability, and survival were analyzed in the full cohort and in subgroups of special interest such as co-occurring mutations and across PD-L1 expression levels. - Results - We analyzed 163 patients who received sotorasib after a median of two treatment lines (range, 0 to 7). Every fourth patient had a poor performance status and 38% had brain metastases (BM). The objective response rate was 38.7%. The median overall survival was 9.8 months (95% CI, 6.5 to not reached). Median real-world (rw) progression-free survival was 4.8 months (9% CI, 3.9 to 5.9). Dose reductions and permanent discontinuation were necessary in 35 (21.5%) and 7 (4.3%) patients, respectively. Efficacy seems to be influenced by PD-L1 expression and a co-occurring KEAP1 mutation. KEAP1 was associated with an inferior survival. Other factors such as BM, STK11, and TP53 mutations had no impact on response and survival. - Conclusion - First results from a real-world population confirm promising efficacy of sotorasib for the treatment of advanced KRAS p.G12C-mutated NSCLC. Patients with co-occurring KEAP1 mutations seem to derive less benefit.
European journal of cancer Amsterdam [u.a.] : Elsevier, 1992 201(2024), Seite 113911
von Felix Saalfeld ; Johanna Möller ; Petros Christopoulos ; Carina Wenzel ; Anna Rasokat ; Xuejun Alice Wang ; Ioannis Ioannis Vathiotis ; David König ; Oliver Illini ; Christian Grohé ; Marcel Wiesweg ; Claas Wesseler ; Christoph Schubart ; Natalie Pelusi ; Gernot Gerhard Ulrich Rohde ; Tobias R. Overbeck ; Jutta Kirfel ; Jürgen Alt ; Diego Kauffmann-Guerrero ; Frank Griesinger ; Jonas Kulhavy ; Michael Allgäuer ; Anna Klimova ; Maret Schütz ; Daniela E. Aust ; Maximilian Hochmair ; Sacha I. Rothschild ; Konstantinos N. Syrigos ; Rajwanth Veluswamy ; Sebastian Michels ; Albrecht Stenzinger ; Korinna Jöhrens ; Martin Wermke
von Julie George ; Lukas Maas ; Nima Abedpour ; Maria Cartolano ; Laura Kaiser ; Rieke Nila Fischer ; Andreas H. Scheel ; Jan-Philipp Weber ; Martin Hellmich ; Graziella Bosco ; Caroline Volz ; Christian Müller ; Ilona Dahmen ; Felix John ; Cleidson Padua Alves ; Lisa Werr ; Jens Peter Panse ; Martin Kirschner ; Walburga Engel-Riedel ; Jessica Jürgens ; Erich Stoelben ; Michael Brockmann ; Stefan Grau ; Martin Sebastian ; Jan Alexander Stratmann ; Jens Kern ; Horst-Dieter Hummel ; Balazs Hegedus ; Martin Schuler ; Till Plönes ; Clemens Aigner ; Thomas Elter ; Karin Toepelt ; Yon-Dschun Ko ; Sylke Kurz ; Christian Grohé ; Monika Serke ; Katja Anne Höpker ; Lars Gerd Hagmeyer ; Fabian Doerr ; Khosro Hekmath ; Judith Strapatsas ; Karl-Otto Kambartel ; Geothy Chakupurakal ; Annette Hülsmeyer ; Franz-Georg Bauernfeind ; Frank Griesinger ; Anne Lüers ; Wiebke Dirks ; Rainer Gerhard Wiewrodt ; Andrea Luecke ; Ernst Michael Rodermann ; Andreas Diel ; Volker Hagen ; Kai Severin ; Roland Ullrich ; Christian Reinhardt ; Alexander Quaas ; Magdalena Bogus ; Cornelius Courts ; Peter Nürnberg ; Kerstin Becker ; Viktor Achter ; Reinhard Büttner ; Jürgen Wolf ; Martin Peifer ; Roman Thomas
