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Transitioning the Molecular Tumor Board from Proof of Concept to Clinical Routine: A German Single-Center Analysis.

ABSTRACT: Molecular precision oncology faces two major challenges: first, to identify relevant and actionable molecular variants in a rapidly changing field and second, to provide access to a broad patient population. Here, we report a four-year experience of the Molecular Tumor Board (MTB) of the Comprehensive Cancer Center Freiburg (Germany) including workflows and process optimizations. This retrospective single-center study includes data on 488 patients enrolled in the MTB from February 2015 through December 2018. Recommendations include individual molecular diagnostics, molecular stratified therapies, assessment of treatment adherence and patient outcomes including overall survival. The majority of MTB patients presented with stage IV oncologic malignancies (90.6%) and underwent an average of 2.1 previous lines of therapy. Individual diagnostic recommendations were given to 487 patients (99.8%). A treatment recommendation was given in 264 of all cases (54.1%) which included a molecularly matched treatment in 212 patients (43.4%). The 264 treatment recommendations were implemented in 76 patients (28.8%). Stable disease was observed in 19 patients (25.0%), 17 had partial response (22.4%) and five showed a complete remission (6.6%). An objective response was achieved in 28.9% of cases with implemented recommendations and for 4.5% of the total population (22 of 488 patients). By optimizing the MTB workflow, case-discussions per session increased significantly while treatment adherence and outcome remained stable over time. Our data demonstrate the feasibility and effectiveness of molecular-guided personalized therapy for cancer patients in a clinical routine setting showing a low but robust and durable disease control rate over time.

SUBMITTER: Hoefflin R

PROVIDER: S-EPMC7962829 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Transitioning the Molecular Tumor Board from Proof of Concept to Clinical Routine: A German Single-Center Analysis.

Hoefflin Rouven R Lazarou Adriana A Hess Maria Elena ME Reiser Meike M Wehrle Julius J Metzger Patrick P Frey Anna Verena AV Becker Heiko H Aumann Konrad K Berner Kai K Boeker Martin M Buettner Nico N Dierks Christine C Duque-Afonso Jesus J Eisenblaetter Michel M Erbes Thalia T Fritsch Ralph R Ge Isabell Xiang IX Geißler Anna-Lena AL Grabbert Markus M Heeg Steffen S Heiland Dieter Henrik DH Hettmer Simone S Kayser Gian G Keller Alexander A Kleiber Anita A Kutilina Alexandra A Mehmed Leman L Meiss Frank F Poxleitner Philipp P Rawluk Justyna J Ruf Juri J Schäfer Henning H Scherer Florian F Shoumariyeh Khalid K Tzschach Andreas A Peters Christoph C Brummer Tilman T Werner Martin M Duyster Justus J Lassmann Silke S Miething Cornelius C Boerries Melanie M Illert Anna L AL von Bubnoff Nikolas N

Cancers 20210308 5

Molecular precision oncology faces two major challenges: first, to identify relevant and actionable molecular variants in a rapidly changing field and second, to provide access to a broad patient population. Here, we report a four-year experience of the Molecular Tumor Board (MTB) of the Comprehensive Cancer Center Freiburg (Germany) including workflows and process optimizations. This retrospective single-center study includes data on 488 patients enrolled in the MTB from February 2015 through D ...[more]

PMID: 33800365

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Project description:Dramatic advances in our understanding of the molecular pathophysiology of cancer, along with a rapidly expanding portfolio of molecular targeted drugs, have led to a paradigm shift toward personalized, biomarker-driven cancer treatment. Here, we report the 2-year experience of the Comprehensive Cancer Center Freiburg Molecular Tumor Board (MTB), one of the first interdisciplinary molecular tumor conferences established in Europe. The role of the MTB is to recommend personalized therapy for patients with cancer beyond standard-of-care treatment. This retrospective case series includes 198 patients discussed from March 2015 through February 2017. The MTB guided individual molecular diagnostics, assessed evidence of actionability of molecular alterations, and provided therapy recommendations, including approved and off-label treatments as well as available matched clinical trials. The majority of patients had metastatic solid tumors (73.7%), mostly progressive (77.3%) after a mean of 2.0 lines of standard treatment. Diagnostic recommendations resulted in 867 molecular diagnostic tests for 172 patients (five per case), including exome analysis in 36 cases (18.2%). With a median turnaround time of 28 days, treatment recommendations were given to 104 patients (52.5%). These included single-agent targeted therapies (42.3%), checkpoint inhibitors (37.5%), and combination therapies (18.3%). Treatment recommendations were implemented in 33 of 104 patients (31.7%), of whom 19 (57.6%) showed stable disease or partial response, including 14 patients (7.1% of the entire population) receiving off-label treatments. Personalized extended molecular-guided patient care is effective for a small but clinically meaningful proportion of patients in challenging clinical situations. Limited access to targeted drugs, lack of trials, and submission at late disease stage prevents broader applicability, whereas genome-wide analyses are not a strict requirement for predictive molecular testing.

Project description:BackgroundThe Multidisciplinary Tumor Board (MTB) is a collaborative platform involving specialists in oncology, surgery, radiology, pathology, and radiotherapy, and aims to optimize diagnostics and treatments. Despite MTB's widespread benefits, limited literature addresses its application in pediatric neuro-oncology. After a literature revision on pediatric neuro-oncology MTB, our study describes our institute's pediatric neuro-oncology MTB, focuses on evaluating its impact and the neuroradiologist's role in patient-centric approaches, considering recent genetic insights into pediatric brain tumors.Materials and methodsLiterature Review concerning pediatric neuro-oncology MTB from January 2002 to June 2024.Clinical dataretrospective study of all patient files presented in the pediatric neuro-oncology MTB (pnMTB) between 2019 and 2022. Statistical analysis was mainly carried out by directly comparing the absolute or relative values of the respective parameters examined; qualitative variables compared mainly with the chi-square test, quantitative variables mainly with the t-test.ResultsLiterature Review: 7 papers encompass a multidisciplinary approach for the pediatric CNS tumors.Clinical dataA total of 236 discussions were analyzed representing 107 patients. Median age was 14,3 years (range: 6 months - 17 years). The requests for case evaluations primarily came from the pediatric oncologists (83%) and neurosurgeons (14.8%), and they were mainly addressed to the neuroradiologists (70.3%). Proposals during pnMTB mainly involved imaging follow-up (47.8%) and management with chemotherapy (34.7%). Changes in patient treatment (CPT) occurred in 115 cases, and pediatric neuroradiologist intervention contributed to 72.4% of these changes.ConclusionThanks to their multidisciplinarity, high number of cases discussed, and usual respect for their proposals, the pnMTB has made it possible to improve the coordination among specialties involved in patient management, to apply the recent protocols, and to exchange knowledge among teams managing pediatric CNS tumors.

Project description:Introduction and objectivesFibrosis, including hypertrophic scar formation, is a pathological condition characterized by excessive production and accumulation of collagen, and loss of tissue architecture, in response to wound healing. Alterations in the extracellular matrix (ECM) biomechanical properties may be important in modulating myofibroblasts and fibrosis formation. The acoustic subcision device uses rapid acoustic pulse technology to noninvasively improve the appearance of hypertrophic scars through both microdisruption of scar tissue matrix and downregulation of fibrotic fibroblasts leading to scar remodeling. The objective of this single-site proof-of-concept IRB-approved human clinical study was to evaluate the efficacy of acoustic subcision device for the improvement in the appearance of hypertrophic scars.MethodEleven hypertrophic scars in 10 participants were treated with a single 6-minute acoustic subcision application without anesthesia. Posttreatment adverse events (AEs) and tolerability were recorded. At 12 and 89 weeks posttreatment, scar heights and volumes were measured, and participant satisfaction questionnaires were completed. Finally, at the last visit the scar appearance was assessed by the Principal Investigator (PI) using the Mecott Modified Scar Scale (MMSS).ResultsImmediately following the acoustic subcision treatment, only mild, moderate erythema or pinpoint bleeding were noted. The treatment sessions were considered tolerable by all participants with an average pain score of 2.2 (on a 0-10 pain score with 10 being the worse possible pain). The 12- and 89-week assessments demonstrated mean height reductions of 46.3% and 56.8%, respectively from baseline. The differences in scar height were statistically significant (p < 0.01). The 12- and 89-week assessments demonstrated a mean volume reduction of 63.2% and 58.1% respectively from baseline. The differences in the scar volume were statistically significant (p < 0.001). The PI graded an average improvement of 33.7% in scar appearance using the MMSS, a statistically significant change (p < 0.001). Finally, >90% of participants reported satisfaction with the improvement in their scar.ConclusionThis proof-of-concept study showed that a single noninvasive acoustic subcision treatment session can safely provide statistically significant improvement in the appearance of hypertrophic scars with minimal treatment pain and meaningful participant satisfaction. More work is needed on a larger number of scars to verify this finding. Further improvement in appearance is expected with multiple acoustic subcision treatments and/or treatments in combination with currently available options. Additional trials to verify this are planned.

Dataset Information

Transitioning the Molecular Tumor Board from Proof of Concept to Clinical Routine: A German Single-Center Analysis.

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Transitioning the Molecular Tumor Board from Proof of Concept to Clinical Routine: A German Single-Center Analysis.

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