Elena Fountzilas

Physicians’ experience, practice and education, on genetic testing and genetic counseling: a nationwide survey study in Greece

Genetic testing has been implemented in clinical practice. However, data on physician's practices and education related to cancer genetics, risk assessment and clinical management in Greece, is limited. In Greece, genetic counseling is performed by treating physicians in collaboration with clinical laboratory geneticists due to the absence of medical geneticists and genetic counsellors. We evaluated treating physicians' experience on genetic testing for hereditary cancer and counseling practices in Greece, thus providing critical areas for improvement of genetic counseling processes. A 28-question survey was used to assess physicians' experience with genetic testing practices, factors that affect their clinical management and decision making and limitations in their education. Of 250 physicians, 208 (83%) completed the survey; of whom 89 (42.8%) were medical oncologists, 88 general surgeons (42.3%), 26 gynecologists (12.5%) and 5 (2.4%) of other specialties. Overall, 91.8% of participants referred patients for genetic testing, with 51.8% recommending multigene panel testing. While most clinicians (84%) reported lack of a clinical genetics department at their institution, 75.7% referred patients for genetic counseling at available departments or healthcare professionals with expertise in genetic counseling. Overall, 68.8% of respondents reported no training or moderate training on cancer genetics. A higher proportion of medical oncologists reported sufficient/very satisfactory training (40.9%) compared to general surgeons (27.3%) or gynecologists (11.5%) (p = 0.012). Time spent on pre- and post-testing sessions varied significantly among respondents. Of 199 physicians, 70% would manage patients with BRCA1 VUS as patients with pathogenic variants, mainly surgeons (83.1%) and gynecologists (80%), compared to oncologists (52.3%) (p < 0.001). Additionally, 64% of physicians treating patients with breast and ovarian cancer would recommend an intervention based on the presence of a BRCA1 VUS. Most respondents (87%) were interested in receiving additional education on cancer risk assessment. Limited consensus was observed during physicians' genetic testing, counseling practices and clinical management of patients with increased predisposition to cancer. Our findings highlight the need for improvement in physician education on cancer risk assessment and increase of genetic counseling resources and services.

Microsatellite Instability Is Insufficiently Used as a Biomarker for Lynch Syndrome Testing in Clinical Practice

PURPOSE The pan-cancer presence of microsatellite instability (MSI)–positive tumors demonstrates its clinical utility as an agnostic biomarker for identifying immunotherapy-eligible patients. Additionally, MSI is a hallmark of Lynch syndrome (LS), the most prevalent cancer susceptibility syndrome among patients with colorectal and endometrial cancer. Therefore, MSI-high results should inform germline genetic testing for cancer-predisposing genes. However, in clinical practice, such analysis is frequently disregarded. METHODS A next-generation sequencing (NGS)–based technique was used for MSI analysis in 4,553 patients with various tumor types. Upon request, somatic BRAF gene analysis was conducted. In addition, hereditary testing of cancer-associated genes was performed in MSI-high cases using a capture-based NGS protocol. MLH1 promoter methylation analysis was conducted retrospectively in patients with colorectal and endometrial cancer to further investigate the origin of MSI at the tumor level. RESULTS The MSI positivity rate for the entire cohort was 5.27%. Endometrial, gastric, colorectal, urinary tract, and prostate cancers showed the highest proportion of MSI-high cases (15.69%, 8.54%, 7.40%, 4.55%, and 3.19%, respectively). A minority of 45 patients (22.73%) among the MSI-high cases underwent germline testing to determine whether the mismatch repair pathway deficiency was inherited. 24.44% of those who performed the genetic test carried a pathogenic variant in an LS-associated gene. Three MSI-high individuals had non-LS gene alterations, including BRCA1, BRCA2, and CDKN2A pathogenic variants, indicating the presence of non–LS-associated gene alterations among MSI-high patients. CONCLUSION Although MSI analysis is routinely performed in clinical practice, as many as 77% of MSI-high patients do not undergo LS genetic testing, despite international guidelines strongly recommending it. BRAF and MLH1 methylation analysis could shed light on the somatic origin of MSI in 42.50% of the MSI-high patients; however, MLH1 analysis is barely ever requested in clinical practice.