Literature DB >> 26205736

Implementation of a Molecular Tumor Board: The Impact on Treatment Decisions for 35 Patients Evaluated at Dartmouth-Hitchcock Medical Center.

Laura J Tafe1, Ivan P Gorlov1, Francine B de Abreu1, Joel A Lefferts1, Xiaoying Liu1, Jason R Pettus1, Jonathan D Marotti1, Kasia J Bloch1, Vincent A Memoli1, Arief A Suriawinata1, Konstantin H Dragnev1, Camilo E Fadul1, Gary N Schwartz1, Clinton R Morgan1, Britt M Holderness1, Jason D Peterson1, Gregory J Tsongalis1, Todd W Miller2, Mary D Chamberlin2.   

Abstract

BACKGROUND: Although genetic profiling of tumors is a potentially powerful tool to predict drug sensitivity and resistance, its routine use has been limited because clinicians are often unfamiliar with interpretation and incorporation of the information into practice. We established a Molecular Tumor Board (MTB) to interpret individual patients' tumor genetic profiles and provide treatment recommendations. PATIENTS AND METHODS: DNA from tumor specimens was sequenced in a Clinical Laboratory Improvement Amendments-certified laboratory to identify coding mutations in a 50-gene panel (n = 34) or a 255-gene panel (n = 1). Cases were evaluated by a multidisciplinary MTB that included pathologists, oncologists, hematologists, basic scientists, and genetic counselors.
RESULTS: During the first year, 35 cases were evaluated by the MTB, with 32 presented for recommendations on targeted therapies, and 3 referred for potential germline mutations. In 56.3% of cases, MTB recommended treatment with a targeted agent based on evaluation of tumor genetic profile and treatment history. Four patients (12.5%) were subsequently treated with a MTB-recommended targeted therapy; 3 of the 4 patients remain on therapy, 2 of whom experienced clinical benefit lasting >10 months.
CONCLUSION: For the majority of cases evaluated, the MTB was able to provide treatment recommendations based on targetable genetic alterations. The most common reasons that MTB-recommended therapy was not administered stemmed from patient preferences and genetic profiling at either very early or very late stages of disease; lack of drug access was rarely encountered. Increasing awareness of molecular profiling and targeted therapies by both clinicians and patients will improve acceptance and adherence to treatments that could significantly improve outcomes. IMPLICATIONS FOR PRACTICE: Case evaluation by a multidisciplinary Molecular Tumor Board (MTB) is critical to benefit from individualized genetic data and maximize clinical impact. MTB recommendations shaped treatment options for the majority of cases evaluated. In the few patients treated with MTB-recommended therapy, disease outcomes were positive and support genetically informed treatment. ©AlphaMed Press.

Entities:  

Keywords:  Genetic profiling; Molecular tumor board; Next-generation sequencing; Precision medicine; Targeted therapy

Mesh:

Substances:

Year:  2015        PMID: 26205736      PMCID: PMC4571816          DOI: 10.1634/theoncologist.2015-0097

Source DB:  PubMed          Journal:  Oncologist        ISSN: 1083-7159


  29 in total

1.  Comparative genomic analysis of primary versus metastatic colorectal carcinomas.

Authors:  Efsevia Vakiani; Manickam Janakiraman; Ronglai Shen; Rileen Sinha; Zhaoshi Zeng; Jinru Shia; Andrea Cercek; Nancy Kemeny; Michael D'Angelica; Agnes Viale; Adriana Heguy; Philip Paty; Timothy A Chan; Leonard B Saltz; Martin Weiser; David B Solit
Journal:  J Clin Oncol       Date:  2012-06-04       Impact factor: 44.544

2.  Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma.

Authors:  Brett E Johnson; Tali Mazor; Chibo Hong; Michael Barnes; Koki Aihara; Cory Y McLean; Shaun D Fouse; Shogo Yamamoto; Hiroki Ueda; Kenji Tatsuno; Saurabh Asthana; Llewellyn E Jalbert; Sarah J Nelson; Andrew W Bollen; W Clay Gustafson; Elise Charron; William A Weiss; Ivan V Smirnov; Jun S Song; Adam B Olshen; Soonmee Cha; Yongjun Zhao; Richard A Moore; Andrew J Mungall; Steven J M Jones; Martin Hirst; Marco A Marra; Nobuhito Saito; Hiroyuki Aburatani; Akitake Mukasa; Mitchel S Berger; Susan M Chang; Barry S Taylor; Joseph F Costello
Journal:  Science       Date:  2013-12-12       Impact factor: 47.728

3.  Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling.

Authors:  Nikhil Wagle; Caroline Emery; Michael F Berger; Matthew J Davis; Allison Sawyer; Panisa Pochanard; Sarah M Kehoe; Cory M Johannessen; Laura E Macconaill; William C Hahn; Matthew Meyerson; Levi A Garraway
Journal:  J Clin Oncol       Date:  2011-03-07       Impact factor: 44.544

4.  Everolimus for advanced pancreatic neuroendocrine tumors.

Authors:  James C Yao; Manisha H Shah; Tetsuhide Ito; Catherine Lombard Bohas; Edward M Wolin; Eric Van Cutsem; Timothy J Hobday; Takuji Okusaka; Jaume Capdevila; Elisabeth G E de Vries; Paola Tomassetti; Marianne E Pavel; Sakina Hoosen; Tomas Haas; Jeremie Lincy; David Lebwohl; Kjell Öberg
Journal:  N Engl J Med       Date:  2011-02-10       Impact factor: 91.245

5.  Personalized medicine in a phase I clinical trials program: the MD Anderson Cancer Center initiative.

Authors:  Apostolia-Maria Tsimberidou; Nancy G Iskander; David S Hong; Jennifer J Wheler; Gerald S Falchook; Siqing Fu; Sarina Piha-Paul; Aung Naing; Filip Janku; Rajyalakshmi Luthra; Yang Ye; Sijin Wen; Donald Berry; Razelle Kurzrock
Journal:  Clin Cancer Res       Date:  2012-09-10       Impact factor: 12.531

6.  The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data.

Authors:  Ethan Cerami; Jianjiong Gao; Ugur Dogrusoz; Benjamin E Gross; Selcuk Onur Sumer; Bülent Arman Aksoy; Anders Jacobsen; Caitlin J Byrne; Michael L Heuer; Erik Larsson; Yevgeniy Antipin; Boris Reva; Arthur P Goldberg; Chris Sander; Nikolaus Schultz
Journal:  Cancer Discov       Date:  2012-05       Impact factor: 39.397

7.  Update on activities at the Universal Protein Resource (UniProt) in 2013.

Authors: 
Journal:  Nucleic Acids Res       Date:  2012-11-17       Impact factor: 16.971

8.  Predicting the functional impact of protein mutations: application to cancer genomics.

Authors:  Boris Reva; Yevgeniy Antipin; Chris Sander
Journal:  Nucleic Acids Res       Date:  2011-07-03       Impact factor: 16.971

9.  Whole-genome sequencing of matched primary and metastatic hepatocellular carcinomas.

Authors:  Limei Ouyang; Jeeyun Lee; Cheol-Keun Park; Mao Mao; Yujian Shi; Zhuolin Gong; Hancheng Zheng; Yingrui Li; Yonggang Zhao; Guangbiao Wang; Huiling Fu; Jhingook Kim; Ho Yeong Lim
Journal:  BMC Med Genomics       Date:  2014-01-09       Impact factor: 3.063

10.  ClinVar: public archive of relationships among sequence variation and human phenotype.

Authors:  Melissa J Landrum; Jennifer M Lee; George R Riley; Wonhee Jang; Wendy S Rubinstein; Deanna M Church; Donna R Maglott
Journal:  Nucleic Acids Res       Date:  2013-11-14       Impact factor: 16.971

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  35 in total

Review 1.  Precision Oncology Decision Support: Current Approaches and Strategies for the Future.

Authors:  Katherine C Kurnit; Ecaterina E Ileana Dumbrava; Beate Litzenburger; Yekaterina B Khotskaya; Amber M Johnson; Timothy A Yap; Jordi Rodon; Jia Zeng; Md Abu Shufean; Ann M Bailey; Nora S Sánchez; Vijaykumar Holla; John Mendelsohn; Kenna Mills Shaw; Elmer V Bernstam; Gordon B Mills; Funda Meric-Bernstam
Journal:  Clin Cancer Res       Date:  2018-02-02       Impact factor: 12.531

2.  Use of comprehensive genomic profiling to direct point-of-care management of patients with gynecologic cancers.

Authors:  Lorna Rodriguez-Rodriguez; Kim M Hirshfield; Veronica Rojas; Robert S DiPaola; Darlene Gibbon; Mira Hellmann; Sara Isani; Aliza Leiser; Gregory M Riedlinger; Allison Wagreich; Siraj M Ali; Julia A Elvin; Vincent A Miller; Shridar Ganesan
Journal:  Gynecol Oncol       Date:  2016-04       Impact factor: 5.482

3.  Integrating Genomics Into Clinical Pediatric Oncology Using the Molecular Tumor Board at the Memorial Sloan Kettering Cancer Center.

Authors:  Michael V Ortiz; Rachel Kobos; Michael Walsh; Emily K Slotkin; Stephen Roberts; Michael F Berger; Meera Hameed; David Solit; Marc Ladanyi; Neerav Shukla; Alex Kentsis
Journal:  Pediatr Blood Cancer       Date:  2016-04-15       Impact factor: 3.167

4.  Effective quality management practices in routine clinical next-generation sequencing.

Authors:  Francine B de Abreu; Jason D Peterson; Christopher I Amos; Wendy A Wells; Gregory J Tsongalis
Journal:  Clin Chem Lab Med       Date:  2016-05       Impact factor: 3.694

5.  Key Lessons Learned from Moffitt's Molecular Tumor Board: The Clinical Genomics Action Committee Experience.

Authors:  Todd C Knepper; Gillian C Bell; J Kevin Hicks; Eric Padron; Jamie K Teer; Teresa T Vo; Nancy K Gillis; Neil T Mason; Howard L McLeod; Christine M Walko
Journal:  Oncologist       Date:  2017-02-08

6.  Implementation and Clinical Utility of an Integrated Academic-Community Regional Molecular Tumor Board.

Authors:  Mark E Burkard; Dustin A Deming; Benjamin M Parsons; Paraic A Kenny; Marissa R Schuh; Ticiana Leal; Nataliya Uboha; Joshua M Lang; Michael A Thompson; Ruth Warren; Jordan Bauman; Mary S Mably; Jennifer Laffin; Catherine R Paschal; Angela M Lager; Kristy Lee; Kristina A Matkowskyj; Darya G Buehler; William M Rehrauer; Jill Kolesar
Journal:  JCO Precis Oncol       Date:  2017-07-05

7.  Framework for Implementing and Tracking a Molecular Tumor Board at a National Cancer Institute-Designated Comprehensive Cancer Center.

Authors:  Neha M Jain; Lauren Schmalz; Christopher Cann; Adara Holland; Travis Osterman; Katie Lang; Georgia L Wiesner; Tuya Pal; Christine Lovly; Thomas Stricker; Christine Micheel; Justin M Balko; Douglas B Johnson; Ben Ho Park; Wade Iams
Journal:  Oncologist       Date:  2021-09-08

Review 8.  The rise of genomic profiling in ovarian cancer.

Authors:  Rebecca A Previs; Anil K Sood; Gordon B Mills; Shannon N Westin
Journal:  Expert Rev Mol Diagn       Date:  2016-12       Impact factor: 5.225

Review 9.  Clinical Implementation of Novel Targeted Therapeutics in Advanced Breast Cancer.

Authors:  Mary D Chamberlin; Erica B Bernhardt; Todd W Miller
Journal:  J Cell Biochem       Date:  2016-06-03       Impact factor: 4.429

10.  Accelerating precision medicine in metastatic prostate cancer.

Authors:  Joaquin Mateo; Rana McKay; Wassim Abida; Rahul Aggarwal; Joshi Alumkal; Ajjai Alva; Felix Feng; Xin Gao; Julie Graff; Maha Hussain; Fatima Karzai; Bruce Montgomery; William Oh; Vaibhav Patel; Dana Rathkopf; Matthew Rettig; Nikolaus Schultz; Matthew Smith; David Solit; Cora Sternberg; Eliezer Van Allen; David VanderWeele; Jake Vinson; Howard R Soule; Arul Chinnaiyan; Eric Small; Jonathan W Simons; William Dahut; Andrea K Miyahira; Himisha Beltran
Journal:  Nat Cancer       Date:  2020-11-17
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