bims-ovdlit 2021-10-10 papers

Issue of 2021–10–10
two papers selected by
Lara Paracchini, Humanitas Research

Gynecol Oncol. 2021 Sep 30. pii: S0090-8258(21)01329-9. [Epub ahead of print]

Characterization of patients with long-term responses to rucaparib treatment in recurrent ovarian cancer.

OBJECTIVE: To describe molecular and clinical characteristics of patients with high-grade recurrent ovarian carcinoma (HGOC) who had long-term responses to the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib.
METHODS: This post hoc analysis pooled patients from Study 10 (NCT01482715; Parts 2A and 2B; n = 54) and ARIEL2 (NCT01891344; Parts 1 and 2; n = 491). Patients with investigator-assessed complete or partial response per RECIST were classified based on duration of response (DOR): long (≥1 year), intermediate (6 months to <1 year), or short (<6 months). Next-generation sequencing was used to detect deleterious mutations and loss of heterozygosity (LOH) in tumors.
RESULTS: Overall, 25.3% (138/545) of enrolled patients were responders. Of these, 27.5% (38/138) had long-term responses; 28.3% (39/138) were intermediate- and 34.8% (48/138) were short-term responders. Most of the long-term responders harbored a BRCA1 or BRCA2 (BRCA) mutation (71.1%, 27/38), and BRCA structural variants were most frequent among long-term responders (14.8%; 4/27). Responders with HGOC harboring a BRCA structural variant (n = 5) had significantly longer DOR than patients with other mutation types (n = 81; median not reached vs 0.62 years; HR, 0.21; 95% CI, 0.10-0.43; unadjusted p = 0.014). Among responders with BRCA wild-type HGOC, most long- and intermediate-term responders had high genome-wide LOH: 81.8% (9/11) and 76.9% (10/13), respectively, including 7 with deleterious RAD51C, RAD51D, or CDK12 mutations.
CONCLUSION: Among patients who responded to rucaparib, a substantial proportion achieved responses lasting ≥1 year. These analyses demonstrate the relationship between DOR to PARP inhibitor treatment and molecular characteristics in HGOC, such as presence of reversion-resistant BRCA structural variants.

Keywords: Duration of response; Genomics; Ovarian carcinoma; Rucaparib; Safety

DOI: https://doi.org/10.1016/j.ygyno.2021.08.030

Clin Chem. 2021 Oct 09. pii: hvab176. [Epub ahead of print]

Circulating Cell-Free DNA Yield and Circulating-Tumor DNA Quantity from Liquid Biopsies of 12 139 Cancer Patients.

BACKGROUND: The amounts of circulating cell-free DNA (cfDNA) and circulating-tumor DNA (ctDNA) present in peripheral blood liquid biopsies can vary due to preanalytic/analytic variables. In this study, we examined the impact of patient age, sex, stage, and tumor type on cfDNA yield, ctDNA fraction, and estimated ctDNA quantity from a large cohort of clinical liquid biopsy samples.
METHODS: We performed a retrospective analysis of 12 139 consecutive samples received for liquid biopsy (FoundationOne® Liquid) clinical testing.
RESULTS: Significant differences in both cfDNA yield and estimated ctDNA quantity were observed based on the underlying tumor type that initiated the liquid biopsy analysis and the stage of the patient (P < 0.001). In addition, significant differences in ctDNA quantity were present based in both the patient age and sex (P < 0.001). Importantly, we saw a significantly higher success rate of issuing a clinically useful report in patients with higher levels of cfDNA yield and ctDNA quantity (P < 0.001).
CONCLUSIONS: In this study, we show that ctDNA quantity varied significantly based on patient age, sex, stage, and tumor type, which could offer an explanation as to why certain liquid biopsy specimens are more likely to fail sequencing or provide clinically meaningful results. In addition, this could affect future clinical decisions on the blood sample volumes required to allow successful liquid biopsy testing.

DOI: https://doi.org/10.1093/clinchem/hvab176