Physician interpretation of genomic test results and treatment selection

Lauren L. Brusco; Chetna Wathoo; Kenna R. Mills Shaw; Vijaykumar R. Holla; Ann M. Bailey; Amber M. Johnson; Yekaterina B. Khotskaya; Beate C. Litzenburger; Nora S. Sanchez; Jia Zeng; Elmer V. Bernstam; Cathy Eng; Bryan K. Kee; Rodabe N. Amaria; Mark J. Routbort; Gordon B. Mills; John Mendelsohn; Funda Meric-Bernstam

doi:10.1002/cncr.31112

Physician interpretation of genomic test results and treatment selection

Lauren L. Brusco
, Chetna Wathoo
, Kenna R. Mills Shaw
, Vijaykumar R. Holla
, Ann M. Bailey
, Amber M. Johnson
, Yekaterina B. Khotskaya
, Beate C. Litzenburger
, Nora S. Sanchez
, Jia Zeng
, Elmer V. Bernstam
, Cathy Eng
, Bryan K. Kee
, Rodabe N. Amaria
, Mark J. Routbort
, Gordon B. Mills
, John Mendelsohn
, Funda Meric-Bernstam

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

BACKGROUND: Genomic testing is increasingly performed in oncology, but concerns remain regarding the clinician's ability to interpret results. In the current study, the authors sought to determine the agreement between physicians and genomic annotators from the Precision Oncology Decision Support (PODS) team at The University of Texas MD Anderson Cancer Center in Houston regarding actionability and the clinical use of test results. METHODS: On a prospective protocol, patients underwent clinical genomic testing for hotspot mutations in 46 or 50 genes. Six months after sequencing, physicians received questionnaires for patients who demonstrated a variant in an actionable gene, investigating their perceptions regarding the actionability of alterations and clinical use of these findings. Genomic annotators independently classified these variants as actionable, potentially actionable, unknown, or not actionable. RESULTS: Physicians completed 250 of 288 questionnaires (87% response rate). Physicians considered 168 of 250 patients (67%) as having an actionable alteration; of these, 165 patients (98%) were considered to have an actionable alteration by the PODS team and 3 were of unknown significance. Physicians were aware of genotype-matched therapy available for 119 patients (71%) and 48 of these 119 patients (40%) received matched therapy. Approximately 46% of patients in whom physicians regarded alterations as not actionable (36 of 79 patients) were classified as having an actionable/potentially actionable mutation by the PODS team. However, many of these were only theoretically actionable due to limited trials and/or therapies (eg, KRAS). CONCLUSIONS: Physicians are aware of recurrent mutations in actionable genes on “hotspot” panels. As larger genomic panels are used, there may be a growing need for annotation of actionability. Decision support to increase awareness of genomically relevant trials and novel treatment options for recurrent mutations (eg, KRAS) also are needed. Cancer 2018;124:966-72.

Original language	English (US)
Pages (from-to)	966-972
Number of pages	7
Journal	Cancer
Volume	124
Issue number	5
DOIs	https://doi.org/10.1002/cncr.31112
State	Published - Mar 1 2018
Externally published	Yes

Funding

Supported in part by Cancer Prevention Research Institute of Texas grants RP150535 (Precision Oncology Decision Support Core) and RP170668 (Data Science and Informatics Core for Cancer Research); the Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy; National Cancer Institute grant U01CA180964; National Institutes of Health/National Center for Advancing Translational Sciences (NIH/NCATS) grant UL1TR000371 (Center for Clinical and Translational Sciences); the Nellie B. Connally Breast Cancer Research Endowment; The University of Texas MD Anderson Cancer Center Support grant (P30 CA016672); NIH/NCATS grant UL1TR001105 (UT-Southwestern Clinical and Translational Alliance for Research); NIH/National Library of Medicine grants R01 LM011829 and R01 LM01068; and NIH/National Institute of Dental and Craniofacial Research grant R01 DE024166. Cathy Eng has received grants from Daichi and Keryx Biopharma-ceuticals Inc, acted as a paid consultant for Bayer and Sirtex, and acted as a paid member of the Speakers’ Bureau for Genentech for work performed outside of the current study. Gordon B. Mills has received a grant from the Adelson Medical Research Foundation; received a commercial research grant and honoraria from and acted a paid consultant/advisory board member for AstraZeneca; received a commercial research grant from and acted as a paid consultant/ advisory board member for Critical Outcome Technologies; received commercial research grants from the Komen Research Foundation, NanoString Technologies, the Breast Cancer Research Foundation, Karus Therapeutics, Illumina, and Takeda/Millennium Pharmaceuticals; received honoraria from and acted as a paid consultant/advisory board member for Symphogen, MedImmune, ISIS Pharmaceuticals, Lilly, Novartis, ImmunoMet Therapeutics, Allostery, and Tarveda Therapeutics; acted as a paid consultant/ advisory board member for Adventist Health, Catena Pharmaceuticals, Precision Medicine, Provista Diagnostics, SignalChem Life-sciences, and Tau Therapeutics; received a commercial research grant and honoraria from Pfizer for work performed outside of the current study and also has licensed a patent for an HRD assay to Myriad Genetics. John Mendelsohn has acted as a paid member of the Board of Directors for Merrimack Pharmaceuticals. Funda Meric-Bernstam has received grants from Novartis, AstraZeneca, Taiho, Genentech, Calithera, Debiopharm International SA, Bayer, Aileron, Jounce, CytoMx Therapeutics, eFFECTOR, Zymeworks, PUMA, Curis Inc, and Pfizer; acted as a paid consultant for Dialecta and Sumitomo Dainippon Pharma; and acted as a paid member of the advisory board for Inflection Biosciences, Pieris Pharmaceuticals, Darwin Health, GRAIL, Clearlight, and Diagnostics for work performed as part of the current study.

Funders	Funder number
ISIS Pharmaceuticals, Inc
Karus Therapeutics
Komen Research Foundation
Myriad Genetics
NIH National Library of Medicine	R01 LM01068, R01 LM011829
NanoString Technologies
Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy
UT Southwestern
National Institute of Health-National Cancer Institute	U01CA180964
National Institute of Dental and Craniofacial Research	R01DE024166
Breast Cancer Research Foundation
Pfizer
AstraZeneca
Cancer Prevention and Research Institute of Texas	RP170668, RP150535
Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
National Center for Advancing Translational Sciences	UL1TR000371
University of Texas M.D. Anderson Cancer Center	P30 CA016672, UL1TR001105
MedImmune

Keywords

clinical trial
genomics
personalized therapy
precision medicine
somatic mutation

ASJC Scopus subject areas

Oncology
Cancer Research

Access to Document

10.1002/cncr.31112

Cite this

Brusco, L. L., Wathoo, C., Mills Shaw, K. R., Holla, V. R., Bailey, A. M., Johnson, A. M., Khotskaya, Y. B., Litzenburger, B. C., Sanchez, N. S., Zeng, J., Bernstam, E. V., Eng, C., Kee, B. K., Amaria, R. N., Routbort, M. J., Mills, G. B., Mendelsohn, J., & Meric-Bernstam, F. (2018). Physician interpretation of genomic test results and treatment selection. Cancer, 124(5), 966-972. https://doi.org/10.1002/cncr.31112

Brusco, LL, Wathoo, C, Mills Shaw, KR, Holla, VR, Bailey, AM, Johnson, AM, Khotskaya, YB, Litzenburger, BC, Sanchez, NS, Zeng, J, Bernstam, EV, Eng, C, Kee, BK, Amaria, RN, Routbort, MJ, Mills, GB, Mendelsohn, J & Meric-Bernstam, F 2018, 'Physician interpretation of genomic test results and treatment selection', Cancer, vol. 124, no. 5, pp. 966-972. https://doi.org/10.1002/cncr.31112

@article{77ac4a757acd44ec95da11c324b71540,

title = "Physician interpretation of genomic test results and treatment selection",

abstract = "BACKGROUND: Genomic testing is increasingly performed in oncology, but concerns remain regarding the clinician's ability to interpret results. In the current study, the authors sought to determine the agreement between physicians and genomic annotators from the Precision Oncology Decision Support (PODS) team at The University of Texas MD Anderson Cancer Center in Houston regarding actionability and the clinical use of test results. METHODS: On a prospective protocol, patients underwent clinical genomic testing for hotspot mutations in 46 or 50 genes. Six months after sequencing, physicians received questionnaires for patients who demonstrated a variant in an actionable gene, investigating their perceptions regarding the actionability of alterations and clinical use of these findings. Genomic annotators independently classified these variants as actionable, potentially actionable, unknown, or not actionable. RESULTS: Physicians completed 250 of 288 questionnaires (87\% response rate). Physicians considered 168 of 250 patients (67\%) as having an actionable alteration; of these, 165 patients (98\%) were considered to have an actionable alteration by the PODS team and 3 were of unknown significance. Physicians were aware of genotype-matched therapy available for 119 patients (71\%) and 48 of these 119 patients (40\%) received matched therapy. Approximately 46\% of patients in whom physicians regarded alterations as not actionable (36 of 79 patients) were classified as having an actionable/potentially actionable mutation by the PODS team. However, many of these were only theoretically actionable due to limited trials and/or therapies (eg, KRAS). CONCLUSIONS: Physicians are aware of recurrent mutations in actionable genes on “hotspot” panels. As larger genomic panels are used, there may be a growing need for annotation of actionability. Decision support to increase awareness of genomically relevant trials and novel treatment options for recurrent mutations (eg, KRAS) also are needed. Cancer 2018;124:966-72.",

keywords = "clinical trial, genomics, personalized therapy, precision medicine, somatic mutation",

author = "Brusco, \{Lauren L.\} and Chetna Wathoo and \{Mills Shaw\}, \{Kenna R.\} and Holla, \{Vijaykumar R.\} and Bailey, \{Ann M.\} and Johnson, \{Amber M.\} and Khotskaya, \{Yekaterina B.\} and Litzenburger, \{Beate C.\} and Sanchez, \{Nora S.\} and Jia Zeng and Bernstam, \{Elmer V.\} and Cathy Eng and Kee, \{Bryan K.\} and Amaria, \{Rodabe N.\} and Routbort, \{Mark J.\} and Mills, \{Gordon B.\} and John Mendelsohn and Funda Meric-Bernstam",

note = "Publisher Copyright: {\textcopyright} 2017 American Cancer Society",

year = "2018",

month = mar,

day = "1",

doi = "10.1002/cncr.31112",

language = "English (US)",

volume = "124",

pages = "966--972",

journal = "Cancer",

issn = "0008-543X",

publisher = "John Wiley and Sons Inc.",

number = "5",

}

TY - JOUR

T1 - Physician interpretation of genomic test results and treatment selection

AU - Brusco, Lauren L.

AU - Wathoo, Chetna

AU - Mills Shaw, Kenna R.

AU - Holla, Vijaykumar R.

AU - Bailey, Ann M.

AU - Johnson, Amber M.

AU - Khotskaya, Yekaterina B.

AU - Litzenburger, Beate C.

AU - Sanchez, Nora S.

AU - Zeng, Jia

AU - Bernstam, Elmer V.

AU - Eng, Cathy

AU - Kee, Bryan K.

AU - Amaria, Rodabe N.

AU - Routbort, Mark J.

AU - Mills, Gordon B.

AU - Mendelsohn, John

AU - Meric-Bernstam, Funda

PY - 2018/3/1

Y1 - 2018/3/1

N2 - BACKGROUND: Genomic testing is increasingly performed in oncology, but concerns remain regarding the clinician's ability to interpret results. In the current study, the authors sought to determine the agreement between physicians and genomic annotators from the Precision Oncology Decision Support (PODS) team at The University of Texas MD Anderson Cancer Center in Houston regarding actionability and the clinical use of test results. METHODS: On a prospective protocol, patients underwent clinical genomic testing for hotspot mutations in 46 or 50 genes. Six months after sequencing, physicians received questionnaires for patients who demonstrated a variant in an actionable gene, investigating their perceptions regarding the actionability of alterations and clinical use of these findings. Genomic annotators independently classified these variants as actionable, potentially actionable, unknown, or not actionable. RESULTS: Physicians completed 250 of 288 questionnaires (87% response rate). Physicians considered 168 of 250 patients (67%) as having an actionable alteration; of these, 165 patients (98%) were considered to have an actionable alteration by the PODS team and 3 were of unknown significance. Physicians were aware of genotype-matched therapy available for 119 patients (71%) and 48 of these 119 patients (40%) received matched therapy. Approximately 46% of patients in whom physicians regarded alterations as not actionable (36 of 79 patients) were classified as having an actionable/potentially actionable mutation by the PODS team. However, many of these were only theoretically actionable due to limited trials and/or therapies (eg, KRAS). CONCLUSIONS: Physicians are aware of recurrent mutations in actionable genes on “hotspot” panels. As larger genomic panels are used, there may be a growing need for annotation of actionability. Decision support to increase awareness of genomically relevant trials and novel treatment options for recurrent mutations (eg, KRAS) also are needed. Cancer 2018;124:966-72.

AB - BACKGROUND: Genomic testing is increasingly performed in oncology, but concerns remain regarding the clinician's ability to interpret results. In the current study, the authors sought to determine the agreement between physicians and genomic annotators from the Precision Oncology Decision Support (PODS) team at The University of Texas MD Anderson Cancer Center in Houston regarding actionability and the clinical use of test results. METHODS: On a prospective protocol, patients underwent clinical genomic testing for hotspot mutations in 46 or 50 genes. Six months after sequencing, physicians received questionnaires for patients who demonstrated a variant in an actionable gene, investigating their perceptions regarding the actionability of alterations and clinical use of these findings. Genomic annotators independently classified these variants as actionable, potentially actionable, unknown, or not actionable. RESULTS: Physicians completed 250 of 288 questionnaires (87% response rate). Physicians considered 168 of 250 patients (67%) as having an actionable alteration; of these, 165 patients (98%) were considered to have an actionable alteration by the PODS team and 3 were of unknown significance. Physicians were aware of genotype-matched therapy available for 119 patients (71%) and 48 of these 119 patients (40%) received matched therapy. Approximately 46% of patients in whom physicians regarded alterations as not actionable (36 of 79 patients) were classified as having an actionable/potentially actionable mutation by the PODS team. However, many of these were only theoretically actionable due to limited trials and/or therapies (eg, KRAS). CONCLUSIONS: Physicians are aware of recurrent mutations in actionable genes on “hotspot” panels. As larger genomic panels are used, there may be a growing need for annotation of actionability. Decision support to increase awareness of genomically relevant trials and novel treatment options for recurrent mutations (eg, KRAS) also are needed. Cancer 2018;124:966-72.

KW - clinical trial

KW - genomics

KW - personalized therapy

KW - precision medicine

KW - somatic mutation

UR - https://www.scopus.com/pages/publications/85034757278

UR - https://www.scopus.com/pages/publications/85034757278#tab=citedBy

U2 - 10.1002/cncr.31112

DO - 10.1002/cncr.31112

M3 - Article

C2 - 29165790

AN - SCOPUS:85034757278

SN - 0008-543X

VL - 124

SP - 966

EP - 972

JO - Cancer

JF - Cancer

IS - 5

ER -

Physician interpretation of genomic test results and treatment selection

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this