19 The Effect of Cancer Whole Exome Sequencing and Transcriptome Analysis (cWES) on the Utilization of Traditional Molecular Diagnostic Testing and Overall Survival in Pediatric Blood Cancer Care. (11th January 2018)

• Record Type: Journal Article
• Authors: Graf, Thomas; Hsiao, Susan; Mansukhani, Mahesh; Bender, Julia Glade; Sulis, Maria-Luisa; Oberg, Jennifer; Sireci, Anthony
• Is Part Of: American journal of clinical pathology. Volume 149(2018)Supplement 1
• Page Start: S173
• Page End: S174
• Publication Date: 2018-01-11
• Subjects: Diagnosis, Laboratory -- Periodicals; Pathology -- Periodicals; 616.07
• DOI: 10.1093/ajcp/aqx149.388
• Languages: English
• ISSNs: 0002-9173

Abstract

Abstract: Cancer whole exome and transcriptome analysis (cWES) of tumors has the potential to impact cancer diagnosis and treatment through the identification of genetic mutations driving oncogenesis, including single nucleotide variants, small indels, copy number alterations, and gene fusions. While cWES has not yet been widely implemented in pediatric cancer care, it can allow for targeted treatment with mutation-specific agents, and potentially replace traditional molecular and cytogenetic diagnostic testing. We hypothesized that cWES would lead to a decrease in the utilization and cost of traditional molecular diagnostic testing performed as part of cancer diagnosis and treatment. We also hypothesized that profiling would increase overall survival by increasing the use of targeted agents. Seventeen pediatric patients with hematologic malignancies underwent cWES. Their medical records were examined for treatment received, long-term outcome, number of traditional molecular laboratory tests performed, and length of follow-up. These patients were matched to historical control patients who did not undergo sequencing. Matching was performed based on type of disease, risk stratification, number of lines of treatment, and age at diagnosis. Number and cost of molecular diagnostic tests, targeted treatment status, and survival outcomes were compared between sequenced and matched control patients. A matched control was identified for 15 of 17 sequenced patients. We compared the cost of traditional molecular testing between sequenced patients and controls during three treatment periods. The total cost of molecular testing was higher in sequenced patients compared to nonsequenced controls in all three treatment periods: $16, 059 vs $9, 480 during the initial diagnosis period; $9, 873 vs $6, 036 during the relapse period; and $6, 833 vs $3, 459 during the bone marrow transplant period. Notably the follow-up period was longer for controls in all three periods. No significant difference was found in survival between sequenced and nonsequenced patients, with a median survival of 3.10 vs 3.49 years respectively ( P = .6299). Four of 17 (23.5%) sequenced patients received a targeted therapy, compared to 1 of 15 (6.7%) nonsequenced patients. This study is the first known to evaluate the effect of comprehensive genomic profiling on the utilization of traditional molecular diagnostic testing in pediatric cancer, and it did not demonstrate a benefit in terms of decreased utilization or overall survival. Profiling did produce a clinical impact in a subset of patients, although the number of patients who received targeted therapy is too small to evaluate an effect on survival. Due to the shift in practice over time for pediatric cancer patients, this study is limited in its scope by the use of historical controls. Prospective studies with greater numbers of patients are necessary to determine the survival benefit and potential cost effectiveness of this technology.