Category: Study Design
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Creation date and Author: Merry K., July 23rd 2025
Last Update and Author: Merry K., July 23rd 2025
Related questions:
- Main content and results of previous studies/applications of the products to be tested in the study
- Previous studies
Several previous small-scale studies have been initiated to investigate exceptional survivors, which are of relevance to the ROSALIND study:
EXPRESS Study: The lead PI for the Glioblastoma cohort, Dr. Olivia Le Saux at Centre Léon Bérard, has also been designated as a Lead PI for the EXPRESS Study. EXPRESS has been conducted as a multicenter, prospective trial in France, exclusively exploring the association between a low level of genomic alteration and exceptional and unexpected responses to targeted therapies in patients with solid tumors. The primary objective of the study was defined as determining whether tumors characterized by a low level of genomic alteration in genes causally implicated in cancer are associated with exceptional and unexpected responses across anticancer targeted therapies. As of December 2017, 147 patients had been screened in 31 French centers, and 42 patients (including those with breast cancer, kidney carcinoma, melanoma, lung cancer, colorectal cancer, and ovarian cancer) had been enrolled in the study. The link can be found here: https://www.annalsofoncology.org/article/S0923-7534(19)32552-9/fulltext.
National Cancer Institute (NCI) Exceptional Responders Initiative (ERI): This initiative was established to elucidate the molecular underpinnings of exceptional responses to treatment, primarily via chemotherapy, in cancer patients. An exceptional responder was defined as a patient who experienced a partial or complete response to a treatment that is effective in fewer than 10% of similar patients, with the duration of response lasting at least three times longer than the median response time. As of November 21, 2017, the accrual goals for the study had been met. Tissue samples from more than 100 cases had been received and analyzed. In 26 of the 111 patients (23.4%), molecular features potentially explaining exceptional responses were identified, such as the co-occurrence of multiple rare genetic changes in the tumor genome or infiltration of the tumor with specific immune cell populations. According to the researchers, these findings demonstrated that genomic characterization of cancer can reveal genetic alterations contributing to unexpected and long-lasting treatment responses.
Genomic and Immune Landscape of Long-term Survivors of High-grade Serous Ovarian Cancer (HGSC) – Peter MacCallum Cancer Center / USA-Australia joint initiative: In this study, 60 patients with advanced-stage HGSC who survived more than 10 years after diagnosis were analyzed using whole-genome sequencing, transcriptome profiling, and methylome profiling of their primary tumor samples. This dataset was compared with that of 66 short- or moderate-term survivors. Tumors of long-term survivors were found to have multiple alterations in genes associated with DNA repair and more frequent somatic variants resulting in an increased predicted neoantigen load. Patients were clustered into survival groups based on genomic and immune cell signatures, including three subsets of patients with BRCA1 alterations showing distinctly different outcomes. Specific combinations of germline and somatic gene alterations, tumor cell phenotypes, and differential immune responses were suggested to contribute to long-term survival in HGSC.