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

With the increasing availability of genomics, routine analysis of advanced cancers is now feasible. Treatment selection is frequently guided by the molecular characteristics of a patient's tumor, and an increasing number of trials are genomically selected. Furthermore, multiple studies have demonstrated the benefit of therapies that are chosen based upon the molecular profile of a tumor. However, the rapid evolution of genomic testing platforms and emergence of new technologies make interpreting molecular testing reports more challenging. More sophisticated precision oncology decision support services are essential. This review outlines existing tools available for health care providers and precision oncology teams and highlights strategies for optimizing decision support. Specific attention is given to the assays currently available for molecular testing, as well as considerations for interpreting alteration information. This article also discusses strategies for identifying and matching patients to clinical trials, current challenges, and proposals for future development of precision oncology decision support. Clin Cancer Res; 24(12); 2719–31. ©2018 AACR.

[1]  Charles Swanton,et al.  Translational Implications of Tumor Heterogeneity , 2015, Clinical Cancer Research.

[2]  Patients with NTRK Fusions Respond to Targeted Therapies. , 2016, Cancer discovery.

[3]  V A Memoli,et al.  Soluble normal and mutated DNA sequences from single-copy genes in human blood. , 1994, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[4]  Nikhil Wagle,et al.  High-throughput detection of actionable genomic alterations in clinical tumor samples by targeted, massively parallel sequencing. , 2012, Cancer discovery.

[5]  S. Gabriel,et al.  Advances in understanding cancer genomes through second-generation sequencing , 2010, Nature Reviews Genetics.

[6]  S Toikkanen,et al.  Prognostic significance of HER-2 oncoprotein expression in breast cancer: a 30-year follow-up. , 1992, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  Razelle Kurzrock,et al.  Breast Cancer Experience of the Molecular Tumor Board at the University of California, San Diego Moores Cancer Center. , 2015, Journal of oncology practice.

[8]  Jorma Isola,et al.  Preservation of nucleic acids and tissue morphology in paraffin-embedded clinical samples: comparison of five molecular fixatives , 2013, Journal of Clinical Pathology.

[9]  Gert Jan van der Wilt,et al.  Is the $1000 Genome as Near as We Think? A Cost Analysis of Next-Generation Sequencing. , 2016, Clinical chemistry.

[10]  Funda Meric-Bernstam,et al.  Concordance of Genomic Alterations between Primary and Recurrent Breast Cancer , 2014, Molecular Cancer Therapeutics.

[11]  Michael Pawlak,et al.  Multiple Protein Analysis of Formalin-fixed and Paraffin-embedded Tissue Samples with Reverse phase Protein Arrays , 2013, Molecular & Cellular Proteomics.

[12]  J. Troge,et al.  Tumour evolution inferred by single-cell sequencing , 2011, Nature.

[13]  Dara L Aisner,et al.  An Oncogenic NTRK Fusion in a Patient with Soft-Tissue Sarcoma with Response to the Tropomyosin-Related Kinase Inhibitor LOXO-101. , 2015, Cancer discovery.

[14]  Jerry Younger,et al.  Metastatic Breast Cancer With ESR1 Mutation: Clinical Management Considerations From the Molecular and Precision Medicine (MAP) Tumor Board at Massachusetts General Hospital , 2016, The oncologist.

[15]  Kenna R Mills Shaw,et al.  Clinical Use of Precision Oncology Decision Support. , 2017, JCO precision oncology.

[16]  Md Abu Shufean,et al.  "Personalized Cancer Therapy": A Publicly Available Precision Oncology Resource. , 2017, Cancer research.

[17]  Richard B. Schwab,et al.  Detection rate of actionable mutations in diverse cancers using a biopsy-free (blood) circulating tumor cell DNA assay , 2016, Oncotarget.

[18]  Raymond K. Auerbach,et al.  The real cost of sequencing: higher than you think! , 2011, Genome Biology.

[19]  John R Yates,et al.  Mass spectrometry in high-throughput proteomics: ready for the big time , 2010, Nature Methods.

[20]  Lee T. Sam,et al.  Personalized Oncology Through Integrative High-Throughput Sequencing: A Pilot Study , 2011, Science Translational Medicine.

[21]  J. Doroshow,et al.  Molecular analysis for therapy choice: NCI MATCH. , 2014, Seminars in oncology.

[22]  Funda Meric-Bernstam,et al.  Feasibility of Large-Scale Genomic Testing to Facilitate Enrollment Onto Genomically Matched Clinical Trials. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[23]  Yingdong Zhao,et al.  GeneMed: An Informatics Hub for the Coordination of Next-Generation Sequencing Studies that Support Precision Oncology Clinical Trials , 2015, Cancer informatics.

[24]  Prahlad T. Ram,et al.  A pan-cancer proteomic perspective on The Cancer Genome Atlas , 2014, Nature Communications.

[25]  Funda Meric-Bernstam,et al.  The right drugs at the right time for the right patient: the MD Anderson precision oncology decision support platform. , 2015, Drug discovery today.

[26]  Marilyn M. Li,et al.  Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. , 2017, The Journal of molecular diagnostics : JMD.

[27]  Gregory J Tsongalis,et al.  Implementation of a Molecular Tumor Board: The Impact on Treatment Decisions for 35 Patients Evaluated at Dartmouth-Hitchcock Medical Center. , 2015, The oncologist.

[28]  S. Domchek,et al.  Reversion Mutations with Clinical Use of PARP Inhibitors: Many Genes, Many Versions. , 2017, Cancer discovery.

[29]  Laurent Arnould,et al.  Use of dedicated gene panel sequencing using next generation sequencing to improve the personalized care of lung cancer , 2016, Oncotarget.

[30]  Edward S. Kim,et al.  Palbociclib in Patients With Pancreatic and Biliary Cancer With CDKN2A Alterations: Results From the Targeted Agent and Profiling Utilization Registry Study. , 2019, JCO precision oncology.

[31]  Jane C Weeks,et al.  Physicians' attitudes about multiplex tumor genomic testing. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[32]  Gad Getz,et al.  Polyclonal Secondary FGFR2 Mutations Drive Acquired Resistance to FGFR Inhibition in Patients with FGFR2 Fusion-Positive Cholangiocarcinoma. , 2017, Cancer discovery.

[33]  Caroline McNeil,et al.  NCI-MATCH launch highlights new trial design in precision-medicine era. , 2015, Journal of the National Cancer Institute.

[34]  Funda Meric-Bernstam,et al.  Building a personalized medicine infrastructure at a major cancer center. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[35]  Renato Martins,et al.  Validation and implementation of targeted capture and sequencing for the detection of actionable mutation, copy number variation, and gene rearrangement in clinical cancer specimens. , 2014, The Journal of molecular diagnostics : JMD.

[36]  Martin L. Miller,et al.  Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer , 2015, Science.

[37]  Michelle L. McGowan,et al.  “A rising tide lifts all boats”: establishing a multidisciplinary genomic tumor board for breast cancer patients with advanced disease , 2016, BMC Medical Genomics.

[38]  Funda Meric-Bernstam,et al.  Cancer Positive Breast − in Pretreated Advanced Estrogen Receptor Mutations α Emergence of Constitutively Active Estrogen Receptor-Updated , 2014 .

[39]  Vladimir Vacic,et al.  Whole-Exome Sequencing of Metastatic Cancer and Biomarkers of Treatment Response. , 2015, JAMA oncology.

[40]  Yasushi Totoki,et al.  KIF5B-RET fusions in lung adenocarcinoma , 2012, Nature Medicine.

[41]  Francisco Cervantes,et al.  Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. , 2003, The New England journal of medicine.

[42]  Robert S Mannel,et al.  Initiation of a formalized precision medicine program in gynecologic oncology. , 2016, Gynecologic oncology.

[43]  Doron Lipson,et al.  Individualized Molecular Analyses Guide Efforts (IMAGE): A Prospective Study of Molecular Profiling of Tissue and Blood in Metastatic Triple-Negative Breast Cancer , 2016, Clinical Cancer Research.

[44]  Donavan T. Cheng,et al.  Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT): A Hybridization Capture-Based Next-Generation Sequencing Clinical Assay for Solid Tumor Molecular Oncology. , 2015, The Journal of molecular diagnostics : JMD.

[45]  William Pao,et al.  Analysis of Tumor Specimens at the Time of Acquired Resistance to EGFR-TKI Therapy in 155 Patients with EGFR-Mutant Lung Cancers , 2013, Clinical Cancer Research.

[46]  Jeong Eon Lee,et al.  Single-cell RNA-seq enables comprehensive tumour and immune cell profiling in primary breast cancer , 2017, Nature Communications.

[47]  Gary W Procop,et al.  Prospective Clinical Study of Precision Oncology in Solid Tumors. , 2015, Journal of the National Cancer Institute.

[48]  Howard Kaufman,et al.  Clinical Actionability of Comprehensive Genomic Profiling for Management of Rare or Refractory Cancers , 2016, The oncologist.

[49]  Ken Chen,et al.  Implementation of biomarker-driven cancer therapy: existing tools and remaining gaps. , 2014, Discovery medicine.

[50]  Juan Wisnivesky,et al.  Geographic accessibility to clinical trials for advanced cancer in the United States. , 2015, JAMA internal medicine.

[51]  Lee T. Sam,et al.  Transcriptome Sequencing to Detect Gene Fusions in Cancer , 2009, Nature.

[52]  Razelle Kurzrock,et al.  Hyperprogressors after Immunotherapy: Analysis of Genomic Alterations Associated with Accelerated Growth Rate , 2017, Clinical Cancer Research.

[53]  Pierre Validire,et al.  Assessment of Whole Genome Amplification for Sequence Capture and Massively Parallel Sequencing , 2014, PloS one.

[54]  Nicolas Servant,et al.  Functional mutational analysis to assess the oncogenic activity of variant of uncertain significance (VUS) detected in patients included in the SHIVA trial , 2016 .

[55]  Yuan Qi,et al.  Estrogen receptor (ER) mRNA and ER-related gene expression in breast cancers that are 1% to 10% ER-positive by immunohistochemistry. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[56]  Kathryn A Phillips,et al.  Challenges of coverage policy development for next-generation tumor sequencing panels: experts and payers weigh in. , 2015, Journal of the National Comprehensive Cancer Network : JNCCN.

[57]  Donavan T. Cheng,et al.  Mutational Landscape of Metastatic Cancer Revealed from Prospective Clinical Sequencing of 10,000 Patients , 2017, Nature Medicine.

[58]  Arul M Chinnaiyan,et al.  Translating cancer genomes and transcriptomes for precision oncology , 2016, CA: a cancer journal for clinicians.

[59]  Dennis C. Friedrich,et al.  Whole-exome sequencing and clinical interpretation of formalin-fixed , paraffin-embedded tumor samples to guide precision cancer medicine , 2014 .

[60]  William Pao,et al.  Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. , 2014, JAMA.

[61]  G. Plitas,et al.  Regulatory T Cells Exhibit Distinct Features in Human Breast Cancer. , 2016, Immunity.

[62]  Ariel Birnbaum,et al.  Clinical Trial Accrual Targeting Genomic Alterations After Next-Generation Sequencing at a Non-National Cancer Institute-Designated Cancer Program. , 2016, Journal of oncology practice.

[63]  Howard L. McLeod,et al.  Key Lessons Learned from Moffitt's Molecular Tumor Board: The Clinical Genomics Action Committee Experience. , 2017, The oncologist.

[64]  Aleksandar Sekulic,et al.  Pilot Trial of Selecting Molecularly Guided Therapy for Patients with Non–V600 BRAF-Mutant Metastatic Melanoma: Experience of the SU2C/MRA Melanoma Dream Team , 2015, Molecular Cancer Therapeutics.

[65]  Benjamin S. Glicksberg,et al.  Development and clinical application of an integrative genomic approach to personalized cancer therapy , 2016, Genome Medicine.

[66]  Jeffrey W. Clark,et al.  Crizotinib in ROS 1-Rearranged Non – Small-Cell Lung Cancer , 2014 .

[67]  Peiyong Jiang,et al.  Cancer genome scanning in plasma: detection of tumor-associated copy number aberrations, single-nucleotide variants, and tumoral heterogeneity by massively parallel sequencing. , 2013, Clinical chemistry.

[68]  F. Cappuzzo,et al.  First-line crizotinib versus chemotherapy in ALK-positive lung cancer. , 2014, The New England journal of medicine.

[69]  E. Mardis,et al.  Prioritizing targets for precision cancer medicine. , 2014, Annals of oncology : official journal of the European Society for Medical Oncology.

[70]  Peter Horak,et al.  Integrating next-generation sequencing into clinical oncology: strategies, promises and pitfalls , 2016, ESMO Open.

[71]  R. Schilsky,et al.  Challenges in initiating and conducting personalized cancer therapy trials: perspectives from WINTHER, a Worldwide Innovative Network (WIN) Consortium trial. , 2015, Annals of oncology : official journal of the European Society for Medical Oncology.

[72]  M. Ladanyi,et al.  Clinical Course of Patients with Non–Small Cell Lung Cancer and Epidermal Growth Factor Receptor Exon 19 and Exon 21 Mutations Treated with Gefitinib or Erlotinib , 2006, Clinical Cancer Research.