bims-ovdlit 2023-09-17 papers

Issue of 2023–09–17
three papers selected by
Lara Paracchini, Humanitas Research

J Immunother Cancer. 2023 Sep;pii: e006013. [Epub ahead of print]11(9):

Cell-free DNA approaches for cancer early detection and interception.

Jamie E Medina, Nicholas C Dracopoli, Peter B Bach, Anna Lau, Robert B Scharpf, Gerrit A Meijer, Claus Lindbjerg Andersen, Victor E Velculescu.

Rapid advancements in the area of early cancer detection have brought us closer to achieving the goals of finding cancer early enough to treat or cure it, while avoiding harms of overdiagnosis. We evaluate progress in the development of early cancer detection tests in the context of the current principles for cancer screening. We review cell-free DNA (cfDNA)-based approaches using mutations, methylation, or fragmentomes for early cancer detection. Lastly, we discuss the challenges in demonstrating clinical utility of these tests before integration into routine clinical care.

Keywords: Biomarkers, Tumor; Neoplastic Cells, Circulating; Review

DOI: https://doi.org/10.1136/jitc-2022-006013

Trends Cancer. 2023 Sep 13. pii: S2405-8033(23)00170-X. [Epub ahead of print]

Circulating cell-free DNA-based early detection.

Kai Zhang, Ruiqing Fu, Rui Liu, Zhixi Su.

Patients benefit considerably from early detection of cancer. Existing single-cancer tests have various limitations, which could be effectively addressed by circulating cell-free DNA (cfDNA)-based multi-cancer early detection (MCED). With sensitive detection and accurate localization of multiple cancer types at a very low and fixed false-positive rate (FPR), MCED has great potential to revolutionize early cancer detection. Herein, we review state-of-the-art approaches for cfDNA-based MCED and their limitations and discuss both technical and clinical challenges in the development and application of MCED tests. Given the constant improvements in technology and understanding of cancer biology, we propose that a cfDNA-based targeted sequencing assay that integrates multimodal features should be optimized for MCED.

Keywords: DNA methylation; cancer screening; circulating cell-free DNA (cfDNA); fragmentomics; multi-cancer early detection (MCED); tissue of origin (TOO)

DOI: https://doi.org/10.1016/j.trecan.2023.08.010

Lancet Oncol. 2023 Sep 11. pii: S1470-2045(23)00396-0. [Epub ahead of print]

Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy in patients with advanced ovarian cancer (OVHIPEC-1): final survival analysis of a randomised, controlled, phase 3 trial.

S Lot Aronson, Marta Lopez-Yurda, Simone N Koole, Jules H Schagen van Leeuwen, Hendrik W R Schreuder, Ralph H M Hermans, Ignace H J T de Hingh, Mignon D J M van Gent, Henriëtte J G Arts, Maaike A P C van Ham, Peter A van Dam, Peter Vuylsteke, Arend G J Aalbers, Victor J Verwaal, Koen K Van de Vijver, Neil K Aaronson, Gabe S Sonke, Willemien J van Driel.

BACKGROUND: The OVHIPEC-1 trial previously showed that the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery resulted in improved progression-free and overall survival compared with cytoreductive surgery alone at 4·7 years of follow-up in patients with stage III epithelial ovarian cancer who were ineligible for primary cytoreduction. We report the final survival outcomes after 10 years of follow-up.
METHODS: In this open-label, randomised, controlled, phase 3 trial, patients with primary epithelial stage III ovarian cancer were recruited at eight HIPEC centres in the Netherlands and Belgium. Patients were eligible if they were aged 18-76 years, had not progressed during at least three cycles of neoadjuvant carboplatin plus paclitaxel, had a WHO performance status score of 0-2, normal blood counts, and adequate renal function. Patients were randomly assigned (1:1) to undergo interval cytoreductive surgery without HIPEC (surgery group) or with HIPEC (100 mg/m2 cisplatin; surgery-plus-HIPEC group). Randomisation was done centrally by minimisation with a masked web-based allocation procedure at the time of surgery when residual disease smaller than 10 mm diameter was anticipated, and was stratified by institution, previous suboptimal cytoreductive surgery, and number of abdominal regions involved. The primary endpoint was progression-free survival and a secondary endpoint was overall survival, analysed in the intention-to-treat population (ie, all randomly assigned patients). This study is registered with ClinicalTrials.gov, NCT00426257, and is closed.
FINDINGS: Between April 1, 2007, and April 30, 2016, 245 patients were enrolled and followed up for a median of 10·1 years (95% CI 8·4-12·9) in the surgery group (n=123) and 10·4 years (95% CI 9·5-13·3) in the surgery-plus-HIPEC group (n=122). Recurrence, progression, or death occurred in 114 (93%) patients in the surgery group (median progression-free survival 10·7 months [95% CI 9·6-12·0]) and 109 (89%) patients in the surgery-plus-HIPEC group (14·3 months [12·0-18·5]; hazard ratio [HR] 0·63 [95% CI 0·48-0·83], stratified log-rank p=0·0008). Death occurred in 108 (88%) patients in the surgery group (median overall survival 33·3 months [95% CI 29·0-39·1]) and 100 (82%) patients in the surgery-plus-HIPEC group (44·9 months [95% CI 38·6-55·1]; HR 0·70 [95% CI 0·53-0·92], stratified log-rank p=0·011).
INTERPRETATION: These updated survival results confirm the long-term survival benefit of HIPEC in patients with primary stage III epithelial ovarian cancer undergoing interval cytoreductive surgery.
FUNDING: Dutch Cancer Foundation (KWF Kankerbestrijding).

DOI: https://doi.org/10.1016/S1470-2045(23)00396-0