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. 2018 Aug 16:2:PO.18.00105.
doi: 10.1200/PO.18.00105. eCollection 2018.

Personalized Clinical Decision Making Through Implementation of a Molecular Tumor Board: A German Single-Center Experience

Rouven Hoefflin  1 , Anna-Lena Geißler  1 , Ralph Fritsch  1 , Rainer Claus  1 , Julius Wehrle  1 , Patrick Metzger  1 , Meike Reiser  1 , Leman Mehmed  1 , Lisa Fauth  1 , Dieter Henrik Heiland  1 , Thalia Erbes  1 , Friedrich Stock  1 , Agnes Csanadi  1 , Cornelius Miething  1 , Britta Weddeling  1 , Frank Meiss  1 , Dagmar von Bubnoff  1 , Christine Dierks  1 , Isabell Ge  1 , Volker Brass  1 , Steffen Heeg  1 , Henning Schäfer  1 , Martin Boeker  1 , Justyna Rawluk  1 , Elke Maria Botzenhart  1 , Gian Kayser  1 , Simone Hettmer  1 , Hauke Busch  1 , Christoph Peters  1 , Martin Werner  1 , Justus Duyster  1 , Tilman Brummer  1 , Melanie Boerries  1 , Silke Lassmann  1 , Nikolas von Bubnoff  1
Affiliations

Personalized Clinical Decision Making Through Implementation of a Molecular Tumor Board: A German Single-Center Experience

Rouven Hoefflin et al. JCO Precis Oncol. .

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. 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. Rouven HoefflinEmployment: Roche Pharma AG (I)Anna-Lena GeißlerNo relationship to discloseRalph FritschHonoraria: Genentech, Servier, Merck, Amgen Consulting or Advisory Role: Genentech Travel, Accommodations, Expenses: Amgen, Celgene, Servier, MerckRainer ClausStock and Other Ownership Interests: Medigene, Evotec Honoraria: Roche, Abbvie, Novartis, Janssen Oncology, Gilead Sciences Consulting or Advisory Role: Abbvie, Roche, Janssen Oncology Speakers' Bureau: Janssen Oncology, Roche Travel, Accommodations, Expenses: Janssen Oncology, AbbvieJulius WehrleTravel, Accommodations, Expenses: PharmaMar, NovartisPatrick MetzgerNo relationship to discloseMeike ReiserTravel, Accommodations, Expenses: AstraZenecaLeman MehmedNo relationship to discloseLisa FauthNo relationship to discloseDieter Henrik HeilandNo relationship to discloseThalia ErbesHonoraria: Roche, Novartis, Teva, Pfizer, AstraZeneca, EisaiFriedrich StockNo relationship to discloseAgnes CsanadiNo relationship to discloseCornelius MiethingConsulting or Advisory Role: Roche Pharma AG, Novartis Travel, Accommodations, Expenses: CelgeneBritta WeddelingNo relationship to discloseFrank MeissHonoraria: Bristol-Myers Squibb, Novartis, MSD Oncology Consulting or Advisory Role: Bristol-Myers Squibb, Novartis Travel, Accommodations, Expenses: Novartis, Bristol-Myers SquibbDagmar von BubnoffHonoraria: Roche, iOMEDICO AG Travel, Accommodations, Expenses: Bristol-Myers SquibbChristine DierksNo relationship to discloseIsabell GeNo relationship to discloseVolker BrassNo relationship to discloseSteffen HeegNo relationship to discloseHenning SchäferHonoraria: Genentech Consulting or Advisory Role: Bristol-Myers Squibb Travel, Accommodations, Expenses: Bristol-Myers SquibbMartin BoekerNo relationship to discloseJustyna RawlukConsulting or Advisory Role: Roche Pharma AG, Takeda, Boehringer Ingelheim, MSD, Bristol-Myers Squibb, Chugai Pharma, AstraZenecaElke Maria BotzenhartNo relationship to discloseGian KayserNo relationship to discloseSimone HettmerNo relationship to discloseHauke BuschNo relationship to discloseChristoph PetersLeadership: University Medical Center Freiburg Honoraria: University Medical Center Freiburg Travel, Accommodations, Expenses: NovartisMartin WernerHonoraria: Diakovere Consulting or Advisory Role: Roche, Novartis, Johnson & Johnson Research Funding: Agilent (Inst), Novartis (Inst), Roche (Inst)Justus DuysterHonoraria: Novartis, Genentech, Pfizer Consulting or Advisory Role: Novartis, Roche Travel, Accommodations, Expenses: NovartisTilman BrummerNo relationship to discloseMelanie BoerriesNo relationship to discloseSilke LassmannHonoraria: Novartis, AstraZeneca Travel, Accommodations, Expenses: Novartis, AstraZenecaNikolas von BubnoffHonoraria: AstraZeneca, Amgen, Bristol-Myers Squibb Consulting or Advisory Role: Novartis Research Funding: Novartis Travel, Accommodations, Expenses: Novartis

Figures

Fig 1.
Fig 1.
Molecular diagnostic testing. (A) The panels depict the type of molecular diagnostic testing performed (left panel) and specify the number of immunohistochemical stains (one to eight antibodies) per case (middle panel) as well as the type of targeted next-generation sequencing (tNGS) library sequenced (right panel). tNGS was performed either by a custom panel (eight-gene panel), a 48-gene panel (TruSeq Amplicon Cancer Panel, Illumina, San Diego, CA), a 54-gene myeloid panel (TruSight Myeloid Sequencing Panel, Illumina) or a custom BRCA1/2 consortium panel. (B) The bar plot depicts the number of sequence variants detected in tumor DNA of 139 patients using tNGS. The bars indicate the numbers of mutations in a given gene (black) and sequence variants that are annotated in COSMIC (gray). The numbers of actionable mutations is shown in green (drug sensitizing) and red (drug resistance). (C) The bar plot depicts the 30 most frequently somatic mutated genes of 36 patients analyzed by whole-exome sequencing (WES). The colors indicate different tumor entities. Mutations with a variant allele frequency > 10% and a minor allele frequency < 0.001 were considered. The GI tumor category includes liver, pancreas, stomach, and esophagus. CUP, carcinoma of unknown primary; HPV, human papillomavirus; IHC, immunohistochemistry; ISH, in situ hybridization; MSI, microsatellite instability.
Fig 2.
Fig 2.
Flow diagram of patients discussed at the Molecular Tumor Board. Responses were determined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. AB, antibody; Combi, combination; CPI, checkpoint inhibitor; FU, follow-up; NE, not evaluable; PD, progressive disease; PR, partial remission; SD, stable disease; SM, small molecule; TKI, tyrosine kinase inhibitor; TT, targeted therapy.
Fig 3.
Fig 3.
Survival analysis. The Kaplan-Meier curve shows the survival of the following three subgroups of patients with stage IV malignancies (n = 148): patients who implemented the treatment recommendation (Rec. pursued, n = 33), patients who did not implement the treatment recommendation (Rec. not pursued, n = 43; of note: patients who did not receive the recommended therapy because of death before treatment initiation [n = 12] were excluded from analysis), and patients who did not receive a treatment recommendation (n = 72). The curve comparison with the log-rank (Mantel-Cox) test revealed statistical significant differences as shown on graph. OS, overall survival. (*) P < .01.
Fig A1.
Fig A1.
Molecular Tumor Board (MTB) workflow. TOS, Tumorboard Online System.
See this image and copyright information in PMC

References

    1. Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364:2507–2516. - PMC - PubMed
    1. Hoadley KA, Yau C, Wolf DM, et al. Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin. Cell. 2014;158:929–944. - PMC - PubMed
    1. Hyman DM, Puzanov I, Subbiah V, et al. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med. 2015;373:726–736. - PMC - PubMed
    1. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373:1627–1639. - PMC - PubMed
    1. Prahallad A, Sun C, Huang S, et al. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature. 2012;483:100–103. - PubMed