Cristina Mitric

Tumor and germline testing with next generation sequencing in epithelial ovarian cancer: a prospective paired comparison using an 18‐gene panel

Genetic testing in epithelial ovarian cancer (EOC) in Ontario includes germline next‐generation sequencing (NGS) for 19 genes. Additionally, tumor tissue undergoes reflex NGS testing for BRCA1/2 to assess eligibility for PARPi. Although parallel testing confers advantages, this model duplicates healthcare resources. Here, we prospectively assessed the feasibility of tumor‐first multigene testing by comparing tumor tissue with germline testing of peripheral blood. An 18‐gene NGS panel was used to test tumor and germline DNA ( n  = 106 patients). In 26 patients, 27 tumor Tier I or II variants were identified, with 16/27 (59%) being germline pathogenic variants (PV) (13 BRCA1/2 ; 3 other genes) and 11/27 (41%) somatic variants (9 BRCA1/2 ; 2 other). In 51/106 patients, there were no tumor variants (excluding TP53 ), of which one patient had a germline BRCA1 copy number variant deletion in exon 12. Tumor‐first testing detected variant‐positive and variant‐negative germline cases in 105/106 patients (99.1%). Among 50 BRCA ‐negative patients, 14/50 (28%) were homologous recombination deficiency (HRD)‐positive. Therefore, we demonstrate that multigene NGS tumor‐testing is effective in identifying germline variants in EOC with a < 1% false‐negative rate.

Gestational trophoblastic neoplasia: does centralization of care impact clinical management?

International societies advocate for gestational trophoblastic neoplasia referral to designated expert centers. This study assessed the impact of centralization of trophoblastic care on clinical outcomes. A centralized program was implemented in 2018 at two affiliated academic hospitals, Princess Margaret Cancer Center and Mount Sinai Hospital. A retrospective analysis of patients treated between 2000 and 2022 was performed and the clinical outcomes were compared before (2000-2017) and after (2018-2022) centralization. Statistical analyses were performed with significance set as p<0.05. A total of 94 patients with trophoblastic neoplasia were included: 60 pre-centralization and 34 post-centralization, 79.8% low-risk and 18.1% high-risk. Centralization led to significant improvement for: (1) accurate score documentation (from 37.9% to 89.3%,); (2) contraception counseling (from 67.2% to 96.7%); (3) median time from diagnosis to chemotherapy (from 9 days to 1 day); and (4) incomplete follow-up (from 20.7% to 3.3%) (all p<0.05). First-line chemotherapy for low-risk neoplasia was dactinomycin in 47.9% and 87.0% pre- and post-centralization, respectively (p=0.005). The median number of chemotherapy cycles decreased from seven to four (p=0.01), and the median number of consolidation cycles increased from two to three (p<0.001). Serum human chorionic gonadotropin (hCG) levels of 10 000-100 000 IU/L were significantly associated with longer time to hCG normalization and higher risk of resistance to first-line chemotherapy compared with hCG levels <1000 IU/L. Centralization of trophoblastic neoplasia care leads to greater guideline compliance, faster chemotherapy initiation, fewer chemotherapy cycles with optimized consolidation, and enhanced surveillance completion. This supports the establishment of trophoblastic neoplasia expert centers.