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Background/Objectives : Current guidelines recommend Cisplatin/Gemcitabine/Durvalumab as first-line treatment for inoperable or recurrent cholangiocarcinoma (CCA). Molecular tumor boards (MTB) have the expertise to support organ-specific tumor boards with evidence-based treatment recommendations for subsequent lines of treatment, based on genomic tumor data and scientific evidence. This study evaluates the adoption of an MTB at a comprehensive cancer center in Germany and whether actionable genetic alterations are associated with specific imaging phenotypes. Methods : Patients with CCA referred to MTB were enrolled from May 2019 to September 2021. For comparison, a cohort of patients from a second center was included. Data on treatment recommendations, regimens, and survival were collected from prospective registries. Baseline and follow-up contrast-enhanced CT were analyzed according to RECIST 1.1. The chi-square test and t -test were used to compare categorical and continuous variables. Results : 583 patients were referred to the MTB, and 92 patients (47 female/51%) with a mean age of 60.3 ± 11.2 were referred for CCA treatment. 65/92 patients harbored 1-3 targetable mutations. Liver metastases were more frequently observed in patients with targetable mutations (84% vs. 62%). Metastasis to the liver and lung was associated with increased sums of diameters (93 mm and 111 mm vs. 40/73 mm in patients with no liver/lung metastasis). The number of metastases in individual organs was unrelated to treatment targets. Follow-up was available for 25 patients with a median time until imaging progression of 23 weeks. Progression occurred as target progression in 63%, nontarget progression in 13%, and appearance of new lesions in 63%. Conclusions : Most patients with CCA harbored targetable mutations, some were related to disease patterns on imaging. The pattern of treatment response and progression was as diverse as the metastatic spread.

Background: The clinical utility of molecular profiling and targeted therapies for neuro-oncology patients outside of clinical trials is not established. We aimed at investigating feasibility and clinical utility of molecular profiling and targeted therapy in adult patients with advanced tumors in the nervous system within a prospective observational study., Methods: molecular tumor board (MTB)@ZPM (NCT03503149) is a prospective observational precision medicine study for patients with advanced tumors. After inclusion of patients, we performed comprehensive molecular profiling, formulated ranked biomarker-guided therapy recommendations based on consensus by the MTB, and collected prospective clinical outcome data., Results: Here, we present initial data of 661 adult patients with tumors of the nervous system enrolled by December 31, 2021. Of these, 408 patients were presented at the MTB. Molecular-instructed therapy recommendations could be made in 380/408 (93.1%) cases and were prioritized by evidence levels. Therapies were initiated in 86/380 (22.6%) cases until data cutoff. We observed a progression-free survival ratio >1.3 in 31.3% of patients., Conclusions: Our study supports the clinical utility of biomarker-guided therapies for neuro-oncology patients and indicates clinical benefit in a subset of patients. Our data might inform future clinical trials, translational studies, and even clinical care., (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: New diagnostic tools in the field of oncology that became available with introduction of the next generation sequencing call for adjustments in the current clinical workflow. To ensure correct interpretation, newly collected data need to be processed and categorized properly. Thus, current experts in oncology need to be trained and new experts from other fields need to be recruited., Objectives: The molecular tumor board was introduced to bring experts from various specialties together. The goal is to discuss and assess complex oncological cases in the context of new molecular diagnostics and give recommendations regarding individualized therapy., Results: After the introduction of the molecular tumor board 2 years ago, the number of cases processed within the molecular tumor board has increased steadily. Of these patients, 70% exhibit molecular alterations that are relevant to therapy. Preliminary results indicate positive responses to the applied therapies and clear improvements in the progression-free and overall survival of patients who would have been considered "untreatable" in the classical clinical setting., Conclusion: The introduction of new molecular diagnostics makes the establishment of advanced clinical structures mandatory. In this regard, the molecular tumor board continues to gain in importance. Preliminary results point towards a significant impact on the therapy of advanced malignancies. The advancements in sequencing and newly established insights into the interpretation of sequencing results will lead to new therapeutic routes. Inevitably, this will make the molecular tumor board indispensable in the future., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Intrahepatic cholangiocarcinoma (iCCA) has emerged as a promising candidate for precision medicine, especially in the case of activating FGFR2 gene fusions. In addition to fusions, a considerable fraction of iCCA patients reveals FGFR2 mutations, which might lead to uncontrolled activation of the FGFR2 pathway but are mostly of unknown functional significance. A current challenge for molecular tumor boards (MTB) is to predict the functional consequences of such FGFR2 alterations to guide potential treatment decisions. We report two iCCA patients with extracellular and juxtamembrane FGFR2 mutations. After in silico investigation of the alterations and identification of activated FGFR2 downstream targets in tumor specimens by immunohistochemistry and transcriptome analysis, the MTB recommended treatment with an FGFR-inhibiting tyrosine kinase inhibitor. Both patients developed a rapidly detectable and prolonged partial response to treatment. These two cases suggest an approach to characterize further detected FGFR2 mutations in iCCA to enable patients´ selection for a successful application of the FGFR -inhibiting drugs., (© 2021. The Author(s).)

Motivation: Next-generation sequencing has become routine in oncology and opens up new avenues of therapies, particularly in personalized oncology setting. An increasing number of cases also implies a need for a more robust, automated and reproducible processing of long lists of variants for cancer diagnosis and therapy. While solutions for the large-scale analysis of somatic variants have been implemented, existing solutions often have issues with reproducibility, scalability and interoperability., Results: Clinical Variant Annotation Pipeline (ClinVAP) is an automated pipeline which annotates, filters and prioritizes somatic single nucleotide variants provided in variant call format. It augments the variant information with documented or predicted clinical effect. These annotated variants are prioritized based on driver gene status and druggability. ClinVAP is available as a fully containerized, self-contained pipeline maximizing reproducibility and scalability allowing the analysis of larger scale data. The resulting JSON-based report is suited for automated downstream processing, but ClinVAP can also automatically render the information into a user-defined template to yield a human-readable report., Availability and Implementation: ClinVAP is available at https://github.com/PersonalizedOncology/ClinVAP., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2019. Published by Oxford University Press.)

Purpose: Precision oncology connects highly complex diagnostic procedures with patient histories to identify individualized treatment options in interdisciplinary molecular tumor boards (MTBs). Detailed data on MTB-guided treatments and outcome with a focus on advanced GI cancers have not been reported yet., Patients and Methods: Next-generation sequencing of tumor and normal tissue pairs was performed between April 2016 and February 2018. After identification of relevant molecular alterations, available clinical studies or in-label, off-label, or matched experimental treatment options were recommended. Follow-up data and a response assessment that was based on radiologic imaging were recorded., Results: Ninety-six patients were presented to the MTB of Tuebingen University Hospital. Sixteen (17%) showed "pathogenic" or "likely pathogenic" germline variants. Recommendations on the basis of molecular alterations or tumor mutational burden were given for 41 patients (43%). Twenty-five received the suggested drug, and 20 were evaluable for best response assessment. Three patients (15%) reached a partial response (PR), and 6 (30%), stable disease (SD), whereas 11 (55%) had tumor progression (progressive disease). Median progression-free survival (PFS) for all treated and evaluable patients was 2.8 months (range, 1.0-9.0 months), and median overall survival (OS) of all treated patients was 5.2 months (range, 0.1 months to not reached). Patients with SD for ≥ 3 months or PR compared with progressive disease showed both a statistically significant longer median PFS (7.8 months [95% CI, 4.2 to 11.4 months] v 2.2 months [95% CI, 1.5 to 2.8 months], P < .0001) and median OS (18.0 months [95% CI, 10.4 to 25.6 months] v 3.8 months [95% CI, 2.3 to 5.4 months], P < .0001)., Conclusion: Next-generation sequencing diagnostics of advanced GI cancers identified a substantial number of pathogenic or likely pathogenic germline variants and unique individual treatment options. Patients with PR or SD in the course of MTB-recommended treatments seemed to benefit with respect to PFS and OS., Competing Interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). Michael BitzerConsulting or Advisory Role: Bristol-Myers Squibb, Bayer Vital GmbH, EISAI, Ipsen, Lilly Travel, Accommodations, Expenses: Ipsen, CelgeneSaskia BiskupEmployment: CeGaT Stock and Other Ownership Interests: CeGaTMartin SchulzeEmployment: Praxis für Humangenetik TuebingenFranz HilkeHonoraria: Agilent Technologies Research Funding: Novartis (Inst) Travel, Accommodations, Expenses: Agilent TechnologiesKonstantin NikolaouHonoraria: Siemens Healthineers, Bayer Schering Pharma Consulting or Advisory Role: Siemens Healthineers Speakers' Bureau: Siemens Healthineers Research Funding: Siemens Healthineers (Inst), Bayer Schering Pharma (Inst) Travel, Accommodations, Expenses: Siemens Healthineers, Bayer Schering PharmaChristopher SchroederResearch Funding: Illumina (Inst), Novartis (Inst)Olaf RiessHonoraria: AstraZeneca, Takeda/Shire Consulting or Advisory Role: Illumina Research Funding: Illumina (Inst)Falko FendConsulting or Advisory Role: Roche, EUSA PharmaDaniel ZipsResearch Funding: Elekta (Inst), Siemens (Inst), Sennewald (Inst) Travel, Accommodations, Expenses: Elekta (Inst)Martina HinterleitnerTravel, Accommodations, Expenses: Novartis/IpsenLars ZenderLeadership: HeparegeniX GmBH Consulting or Advisory Role: Boehringer Ingelheim Research Funding: HeparegeniX GmBH Patents, Royalties, Other Intellectual Property: Patent on MKK4 Inhibition for the treatment of acute and chronic liver diseases Travel, Accommodations, Expenses: IpsenGhazaleh TabatabaiHonoraria: AbbVie, Bayer, Medac, Novocure (Inst) Consulting or Advisory Role: AbbVie, Bayer Travel, Accommodations, Expenses: Novocure (Inst)Nisar P. MalekHonoraria: Spring Bank Travel, Accommodations, Expenses: Falk Foundation No other potential conflicts of interest were reported., (© 2020 by American Society of Clinical Oncology.)