Abstract 04: Impact of whole exome sequencing results on clinical decision making for pediatric solid tumor patients in the hypothetical scenario of tumor relapse: A survey of pediatric oncologists
Authors: Bavle Abhishek , Wang Tao , Lin Frank Y. , Roy Angshumoy , Kerstein Robin A. , Scollon Sarah , Bergstrom Katie , Gutierrez Stephanie , Ramamurthy Uma , Yang Yaping , Eng Christine M. , Gibbs Richard A. , Chintagumpala Murali M. , Hilsenbeck Susan G. , Plon Sharon E. , Berg Stacey L. , Parsons. D. Williams 
Published: May 2016

Abstract
Background: The development of molecularly-targeted agents has made it possible to personalize therapy for patients by targeting the specific mutations in their tumor. Pediatric clinical trials utilizing such strategies are being planned but little is known about the opinions of pediatric oncologists regarding the utility of genomic data for guiding treatment decisions. The goals of this study were to (1) characterize those opinions in the context of children with relapsed/refractory solid tumors and (2) assess the potential impact of clinical whole exome sequencing (WES) data on medical decision-making in that context.
Methods: As part of the ongoing BASIC3 clinical sequencing study at Texas Children's Cancer Center, clinical germline and tumor (if sample available) WES were performed for unselected newly-diagnosed pediatric CNS and non-CNS solid tumor patients. The primary oncologist for each (n=17) received online surveys for each study patient before and after review of WES reports. The pre- and post-WES surveys asked oncologists to rank options for off-study systemic chemotherapy (of any type) for their patient in the hypothetical scenario of tumor relapse. Oncologists were then asked if they would consider using a molecularly-targeted agent in the context of a clinical trial, and if so, which agents (from a representative list), their rank order and the rationale for those choices. Post-WES surveys also included questions regarding perceived utility of the tumor WES results for patient care. Pre-WES surveys were analyzed for baseline oncologist responses regarding these hypothetical treatment decisions. When available, pre- and post-WES surveys were analyzed as pairs as an initial assessment of the influence of the WES results on the oncologist's choice of therapy.
Results: 177/189 (94%) of pre-WES surveys and 111/161 (69%) post-WES surveys were available for analysis. Analysis of pre-exome surveys revealed that oncologists would recommend systemic chemotherapy for 127/177 (72%) patients in the hypothetical event of tumor relapse but would consider a molecularly-targeted agent off-study as their first option in only 8/177 (4%) cases. In contrast, oncologists indicated that they would consider targeted therapies in the context of a clinical trial for 99/177 (56%) patients, most commonly sorafenib (n=21), cixutumumab (n=17), and crizotinib (n=13). There were 26 cases in which somatic mutations were identified in genes categorized as having established or potential clinical relevance, and for which both pre- and post-WES surveys were available. A corresponding targeted agent was ranked for consideration in the hypothetical scenario of relapse on the post-WES survey for 8/26 (31%) of these patients (somatic mutations in MET, JAK2, HRAS, NRAS X 2, ALK, BRAF, KIT), having only been chosen on the pre-WES survey in 2 of those cases. On 8 of 111 (7%) post-WES surveys, the oncologist removed a targeted agent that had been prioritized on the pre-WES survey after no relevant mutation was detected, including the Sonic Hedgehog inhibitor GDC-0449 in 5 cases.
Conclusion: Although genomic tests such as WES have the potential to identify molecular targets for therapy in children with relapsed tumors, a survey of pediatric oncologists revealed that most consider such therapies as options only in the context of a clinical trial. These findings support the potential utility of WES in precision oncology approaches as well as the need for clinical trials evaluating the use of integrated genomic testing to guide treatment of children with relapsed solid tumors.
Citation Format: Abhishek Bavle, Tao Wang, Frank Y. Lin, Angshumoy Roy, Robin A. Kerstein, Sarah Scollon, Katie Bergstrom, Stephanie Gutierrez, Uma Ramamurthy, Yaping Yang, Christine M. Eng, Richard A. Gibbs, Murali M. Chintagumpala, Susan G. Hilsenbeck, Sharon E. Plon, Stacey L. Berg, D. Williams Parsons. Impact of whole exome sequencing results on clinical decision making for pediatric solid tumor patients in the hypothetical scenario of tumor relapse: A survey of pediatric oncologists. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr 04.