bims-tumhet 2024-09-29 papers

Issue of 2024–09–29
three papers selected by
Sergio Marchini, Humanitas Research

Cochrane Database Syst Rev. 2024 Sep 23. 9 CD015896

Predictive value of homologous recombination deficiency status for survival outcomes in primary tubo-ovarian high-grade serous carcinoma.

Tibor A Zwimpfer, Hannah Ewald, Esra Bilir, Madawa Jayawardana, Christian Appenzeller-Herzog, Nicolò Bizzarri, Zoia Razumova, Joanna Kacperczyk-Bartnik, Viola Heinzelmann-Schwarz, Michael Friedlander, David Dl Bowtell, Dale W Garsed.

OBJECTIVES: This is a protocol for a Cochrane Review (prognosis). The objectives are as follows: To evaluate the predictive value of the prognostic factor HRD status, as determined by various clinically validated HRD assays at the time of staging laparotomy, compared to BRCA1/2 mutation status for progression-free survival and overall survival in patients with tubo-ovarian high-grade serous carcinoma treated in the first-line setting with a combination of surgery and platinum-based chemotherapy and/or maintenance with PARP inhibitors.

DOI: https://doi.org/10.1002/14651858.CD015896

Oncol Lett. 2024 Nov;28(5): 548

Liquid biopsy: Comprehensive overview of circulating tumor DNA (Review).

Qian Ge, Zhi-Yun Zhang, Suo-Ni Li, Jie-Qun Ma, Zheng Zhao.

Traditional tumor diagnosis methods rely on tissue biopsy, which can be invasive and unsuitable for long-term monitoring of tumor dynamics. The advent of liquid biopsy has notably improved the overall management of patients with cancer. Liquid biopsy techniques primarily involve detection of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). The present review focuses on ctDNA because of its significance in tumor diagnosis, monitoring and treatment. The use of ctDNA-based liquid biopsy offers several advantages, including non-invasive or minimally invasive collection methods, the ability to conduct repeated assessment and comprehensive insights into tumor biology. It serves crucial roles in disease management by facilitating screening of high-risk patients, dynamically monitoring therapeutic responses and diagnosis. Furthermore, ctDNA can be used to demonstrate pseudo-progression, monitor postoperative tumor status and guide adaptive treatment plans. The present study provides a comprehensive review of ctDNA, exploring its origins, metabolism, detection methods, clinical role and the current challenges associated with its application.

Keywords: circulating tumor DNA; liquid biopsy; overall tumor management

DOI: https://doi.org/10.3892/ol.2024.14681

J Exp Clin Cancer Res. 2024 Sep 20. 43(1): 264

Role of cfDNA and ctDNA to improve the risk stratification and the disease follow-up in patients with endometrial cancer: towards the clinical application.

BACKGROUND: There has been a rise in endometrial cancer (EC) incidence leading to increased mortality. To counter this trend, improving the stratification of post-surgery recurrence risk and anticipating disease relapse and treatment resistance is essential. Liquid biopsy analyses offer a promising tool for these clinical challenges, though the best strategy for applying them in EC must be defined. This study was designed to determine the value of cfDNA/ctDNA monitoring in improving the clinical management of patients with localized and recurrent disease.
METHODS: Plasma samples and uterine aspirates (UA) from 198 EC patients were collected at surgery and over time. The genetic landscape of UAs was characterized using targeted sequencing. Total cfDNA was analyzed for ctDNA presence based on the UA mutational profile.
RESULTS: High cfDNA levels and detectable ctDNA at baseline correlated with poor prognosis for DFS (p-value < 0.0001; HR = 9.25) and DSS (p-value < 0.0001; HR = 11.20). This remained clinically significant when stratifying tumors by histopathological risk factors. Of note, cfDNA/ctDNA analyses discriminated patients with early post-surgery relapse and the ctDNA kinetics served to identify patients undergoing relapse before any clinical evidence emerged.
CONCLUSIONS: This is the most comprehensive study on cfDNA/ctDNA characterization in EC, demonstrating its value in improving risk stratification and anticipating disease relapse in patients with localized disease. CtDNA kinetics assessment complements current strategies to monitor the disease evolution and the treatment response. Therefore, implementing cfDNA/ctDNA monitoring in clinical routines offers a unique opportunity to improve EC management.
TRANSLATIONAL RELEVANCE: The study demonstrates that high levels of cfDNA and detectable ctDNA at baseline are strong indicators of poor prognosis. This enables more accurate risk stratification beyond traditional histopathological factors, allowing clinicians to identify high-risk patients who may benefit from more aggressive treatment and closer monitoring. Moreover, longitudinal analysis of cfDNA/ctDNA can detect disease recurrence months before clinical symptoms or imaging evidence appear. This early warning system offers a significant advantage in clinical practice, providing a window of opportunity for early intervention and potentially improving patient outcomes.

Keywords: Blood biomarkers; Endometrial cancer; Liquid Biopsy; Prognostic biomarkers; Tumour kinetics

DOI: https://doi.org/10.1186/s13046-024-03158-w