Handbook of Targeted Cancer Therapy and Immunotherapy

92 The surplus of data acquired from broad-based sequencing efforts poses a set of new challenges for oncologists—how can this information be best incorporated into clinical practice to improve outcomes for patients? A survey of physicians at a National Can cer Institute (NCI)-designated comprehensive cancer center identified that physicians have varying levels of confidence regarding the incorporation of genomic data into practice (21). Although many genes have been identified that have prognostic and/or therapeutic relevance, there is a knowledge gap in determining if a particular alteration is a “driver” or “passenger,” and which alterations may be clinically “actionable,” meaning that they may be targeted directly or indirectly with investigational or approved agents (22). Integration of NGS data requires not only the accurate detection of genomic alterations but also an understanding of the clinical implications associated with an alteration, and awareness of trials that the patient may be eligible for (22). Furthermore, ac cess to both multiplex genomic profiling and molecularly targeted therapies varies widely by insti tution (23). A study by Meric-Bernstam et al. reported that few patients with actionable alterations were ultimately enrolled in genotype-matched trials (23). Efforts to address these concerns include decision support programs to assess if a variant is actionable and/or affects eligibility criteria for an ongoing clinical trial (24). Several publicly available precision oncology resources have also been established to help provide insight into the actionability of alterations, including the MD Anderson Personalized Cancer Therapy website (www.personalizedcancertherapy.org) (25), the Cornell Pre cision Medicine Knowledge Base (PMKB) website (https://pmkb.weill.cornell.edu/) (26), and the Memorial Sloan Kettering OncoKB website (https://www.oncokb.org/) (27). These findings high light the need for institutional, programmatic efforts to implement decision support for precision oncology to facilitate the enrollment of patients with actionable alterations into clinical trials. Conclusion High-throughput sequencing has revolutionized modern cancer care and enabled oncologists to routinely profile tumors in clinical practice. Clinical integration of genomic and transcriptomic data obtained from NGS is evolving, and decision support programs can be utilized to assess the functionality of a given aberration, which may facilitate clinical trial enrollment.

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