How to Standardize Molecular Profiling Programs for Routine Patient Care

Abstract

AbstractManagement of patients with advanced cancer includes individualized treatment recommendations guided by molecular profiles. Refined complex molecular and immunological diagnostics are developed in parallel to the rapidly growing number of targeted therapies for defined genetic alterations and novel immunotherapies. For adequate counseling, patients are presented to Molecular Tumor Boards within the framework of precision oncology programs established at virtually all large cancer centers worldwide. The annotation and clinical interpretation of molecular pathology results are carried out by a multiprofessional team of experts formulating individualized treatment recommendations, taking also into account clinical characteristics. The process of annotation and clinical interpretation of molecular events in tumors also considers predictive factors defined in randomized studies as well as clinical judgement. All steps described above are not standardized, resulting in relevant heterogeneity in treatment recommendations among MTBs in different institutions.In this chapter, contemporary challenges will be discussed, including intratumoral heterogeneity, use of diverse molecular diagnostic systems with inherent differences in sensitivity and specificity of detecting genetic alterations; the yet insufficiently addressed need for harmonizing variant annotation and interpretation; and the currently rather intuitive inclusion of multiple further “soft” parameters; all of which may significantly contribute to the current heterogeneity of recommendations.