bims-ovdlit 2023-10-15 papers

Issue of 2023–10–15
three papers selected by
Lara Paracchini, Humanitas Research

Biomed Pharmacother. 2023 Oct 06. pii: S0753-3322(23)01428-2. [Epub ahead of print]168 115630

Circulating tumor DNA-based copy-number profiles enable monitoring treatment effects during therapy in high-grade serous carcinoma.

Mai T N Nguyen, Anna Rajavuori, Kaisa Huhtinen, Sakari Hietanen, Johanna Hynninen, Jaana Oikkonen, Sampsa Hautaniemi.

Circulating tumor DNA (ctDNA) analysis has emerged as a promising tool for detecting and profiling longitudinal genomics changes in cancer. While copy-number alterations (CNAs) play a major role in cancers, treatment effect monitoring using copy-number profiles has received limited attention as compared to mutations. A major reason for this is the insensitivity of CNA analysis for the real-life tumor-fraction ctDNA samples. We performed copy-number analysis on 152 plasma samples obtained from 29 patients with high-grade serous ovarian cancer (HGSC) using a sequencing panel targeting over 500 genes. Twenty-one patients had temporally matched tissue and plasma sample pairs, which enabled assessing concordance with tissues sequenced with the same panel or whole-genome sequencing and to evaluate sensitivity. Our approach could detect concordant CNA profiles in most plasma samples with as low as 5% tumor content and highly amplified regions in samples with ∼1% of tumor content. Longitudinal profiles showed changes in the CNA profiles in seven out of 11 patients with high tumor-content plasma samples at relapse. These changes included focal acquired or lost copy-numbers, even though most of the genome remained stable. Two patients displayed major copy-number profile changes during therapy. Our analysis revealed ctDNA-detectable subclonal selection resulting from both surgical operations and chemotherapy. Overall, longitudinal ctDNA data showed acquired and diminished CNAs at relapse when compared to pre-treatment samples. These results highlight the importance of genomic profiling during treatment as well as underline the usability of ctDNA.

Keywords: Copy-number alterations; CtDNA; High-grade serous carcinoma; Targeted sequencing; Treatment monitoring

DOI: https://doi.org/10.1016/j.biopha.2023.115630

Clin Cancer Res. 2023 Oct 09.

OvaPrint™ - a cell-free DNA methylation liquid biopsy for the risk assessment of high-grade serous ovarian cancer.

David N Buckley, Juan Pablo Lewinger, Gerald Gooden, Monique Spillman, Monica Neuman, X Mona Guo, Ben Yi Tew, Heather Miller, Varun U Khetan, Lee P Shulman, Lynda Roman, Bodour Salhia.

Purpose High-grade serous ovarian carcinoma (HGSOC) is the most lethal epithelial ovarian cancer (EOC) and is often diagnosed at late stage. In women with a known pelvic mass, surgery followed by pathological assessment is the most reliable way to diagnose EOC and there are still no effective screening tools in asymptomatic women. In the current study we developed a cfDNA methylation liquid biopsy for the risk assessment of early-stage HGSOC. Experimental Design We performed reduced representation bisulfite sequencing to identify differentially methylated regions (DMRs) between HGSOC and normal ovarian and fallopian tube tissue. Next, we performed hybridization probe capture for 1677 DMRs and constructed a classifier (OvaPrint™) on an independent set of cfDNA samples to discriminate HGSOC from benign masses. We also analyzed a series of non-HGSOC EOC, including low-grade, and borderline samples to assess the generalizability of OvaPrint™. A total of 372 samples (tissue n=59, plasma n=313) were analyzed in this study. Results OvaPrint™ achieved a positive predictive value of 95% and a negative predictive value of 88% for discriminating HGSOC from benign masses, surpassing other commercial tests. OvaPrint™ was less sensitive for non-HGSOC EOC, albeit it may have potential utility for identifying low-grade and borderline tumors with higher malignant potential. Conclusions OvaPrint™ is a highly sensitive and specific test that can be used for the risk assessment of HGSOC in symptomatic women. Prospective studies are warranted to validate OvaPrint™ for HGSOC and further develop it for non-HGSOC EOC histotypes in both symptomatic and asymptomatic women with adnexal masses.

DOI: https://doi.org/10.1158/1078-0432.CCR-23-1197

Prev Med Rep. 2023 Dec;36 102429

Cervical cancer screening pathways in France in 2015-2021, a nationwide study based on medico-administrative data.

Christine Le Bihan-Benjamin, Céline Audiger, Inès Khati, Frédéric de Bels, Philippe Jean Bousquet, Stéphanie Barré.

To better document cervical cancer screening (CCS) pathways, the purpose of our study was to examine CCS pathways among women who had undergone a screening test (opportunistic or organised programme), based on real-life data over a 7-year period. This study used data from the French national health care database (SNDS), which covers almost 100 % of the French population of around 66 million inhabitants. Data from 2015 to 2021 were extracted. More than one quarter (27 %) of women who were at least 25 years old in 2015 and up to 65 years old in 2021 were not screened over the 2015-2021 period. Compared to women who had undergone screening at least once, women who were not screened were older (36 % vs. 23 % in the 50-59 years age group in 2015) and lived in the most deprived urban areas (21 % vs 16 % for less and most deprived respectively). 57 % of women underwent screening within recommended intervals, 13 % of women were under-screened, and 30 % were overscreened. Overall, our study identified that, in 2021, women who participated in the French organised screening programme were less likely to be screened within the recommended interval over the 7-year period. These analyses need to be continued over time in order to assess whether the programme helps reintegrate women into the screening process.

Keywords: Cancer screening; Cervical cancer; France; Human papillomavirus; Organised cervical cancer; Screening programme; Screening trajectories

DOI: https://doi.org/10.1016/j.pmedr.2023.102429