A practical approach to aid physician interpretation of clinically actionable predictive biomarker results in a multi-platform tumor profiling service

Abstract

Patients in whom the standard of care has failed or who have uncommon tumors for which no standard of care exists are often treated with drugs selected based on the physician’s best guess. The rate of success for this method is generally low. With the advent of fast, affordable tumor profiling technologies, and a growth in the understanding of predictive biomarkers, it is now possible to identify drugs potentially associated with clinical benefit for such patients. We present the Caris approach to evidence-based tumor profiling and two patients with advanced ovarian and prostate cancer in whom standard of care had failed and tumor profiling identified an effective treatment schedule. To establish Caris Molecular IntelligenceTM (CMI), over 120,000 clinical publications were screened and graded to characterize the predictive value of biomarkers that form the panel of tests. CMI includes multiple technologies to measure changes in proteins, ribonucleic acid, and deoxyribonucleic acid and proprietary software that matches the test results with the published evidence. The CMI results enable physicians to select drugs that are more likely to benefit the patients, avoid drugs that are not likely to work, and find treatment options that otherwise would not be considered. Worldwide, over 60,000 cancer patients have undergone evidence-based tumor profiling with CMI. In the cases reported in this article, CMI identified treatments that would not have been routinely used in the respective clinical setting. The clinical outcomes observed help to illustrate the utility of this approach.

Comprehensive genetic testing identifies targetable genomic alterations in most patients with non-small cell lung cancer, specifically adenocarcinoma, single institute investigation

“…Samples sent to FM underwent whole-genome shotgun library construction with hybridization–based capture for 4,557 exons from 287 cancer related genes and 47 introns from 19 genes frequently involved in DNA rearrangements. Samples sent to CMI underwent an established technology platforms to measure a panel of carefully selected biomarkers including immunohistochemistry (IHC), fluorescent in situ hybridization (FISH), polymerase chain reaction (PCR), and direct gene sequencing [ 28 ]. RG paired NGS with FISH and RNA expression markers to identify any clinically targetable genetic alteration in the samples.…”

Developing an electronic geriatric assessment to improve care of older adults with cancer receiving radiotherapy

“…These real-time results being designed for the GA will not only report the answers to the specific questions but also calculate a frailty index [48] , as well as guideline-recommended interventions (see Table 2 ). The result printouts are modeled to be similar to tumor molecular testing results which are delivered both with the relevant mutated and non-mutated genes as well as the systemic agents that may target those mutations [56] . This program would thus make it easier for radiation oncologists without training in geriatrics to interpret and react to the results of the GA appropriately.…”

Practical aspects of NGS-based pathways analysis for personalized cancer science and medicine

“…Other successful clinical examples of genetic analysis for personalized medicine were published in 2014 by Caris company[32]. Using the Caris Molecular Intelligence (CMI) platform - a combination of genome sequencing, FISH (fluorescence in situ hybridization method) and PCR the authors analyzed two patients.…”