Year: 2023
Type: article
Abstract: PURPOSE: To overcome barriers to genomic testing for patients with rare cancers, we initiated a program to offer free clinical tumor genomic testing worldwide to patients with select rare cancer subtypes. EXPERIMENTAL DESIGN: Patients were recruited through social media outreach and engagement with disease-specific advocacy groups, with a focus on patients with histiocytosis, germ cell tumors (GCT), and pediatric cancers. Tumors were analyzed using the MSK-IMPACT next-generation sequencing assay with the return of results to patients and their local physicians. Whole-exome recapture was performed for female patients with GCTs to define the genomic landscape of this rare cancer subtype. RESULTS: A total of 333 patients were enrolled, and tumor tissue was received for 288 (86.4%), with 250 (86.8%) having tumor DNA of sufficient quality for MSK-IMPACT testing. Eighteen patients with histiocytosis have received genomically guided therapy to date, of whom 17 (94%) have had clinical benefit with a mean treatment duration of 21.7 months (range, 6-40+). Whole-exome sequencing of ovarian GCTs identified a subset with haploid genotypes, a phenotype rarely observed in other cancer types. Actionable genomic alterations were rare in ovarian GCT (28%); however, 2 patients with ovarian GCTs with squamous transformation had high tumor mutational burden, one of whom had a complete response to pembrolizumab. CONCLUSIONS: Direct-to-patient outreach can facilitate the assembly of cohorts of rare cancers of sufficient size to define their genomic landscape. By profiling tumors in a clinical laboratory, results could be reported to patients and their local physicians to guide treatment. See related commentary by Desai and Subbiah, p. 2339.
Source: Clinical Cancer Research
Authors: Seyram A. Doe-Tetteh, Sabrina Y. Camp, Dalicia Reales, Jett Crowdis, Anne Marie Noronha, Bernadette Wolff, Tina Alano, Jesse Galle, S. Duygu Selcuklu, Agnes Viale, Nicholas D. Socci, Ying L. Liu, William P. Tew, Carol Aghajanian, Marc Ladanyi, Meng Xiao He, Saud H. AlDubayan, Roei David Mazor, Ofer Shpilberg, Oshrat Hershkovitz-Rokah, Jose A. Riancho, Jose L. Hernandez, M. Carmen Gonzalez-Vela, Justin J. Buthorn, Manda Wilson, Amy E. Webber, Mariko Yabe, Kseniya Petrova-Drus, Marc Rosenblum, Benjamin H. Durham, Omar Abdel-Wahab, Michael F. Berger, Mark T.A. Donoghue, Andrew L. Kung, Julia Glade Bender, Neerav N. Shukla, Samuel A. Funt, Ahmet Dogan, Robert A. Soslow, Hikmat Al-Ahmadie, Darren R. Feldman, Eliezer M. Van Allen, Eli L. Diamond, David B. Solit
Institutions: Memorial Sloan Kettering Cancer Center, Broad Institute, Dana-Farber Cancer Institute, Massachusetts Institute of Technology, Cornell University, Harvard University, King Saud bin Abdulaziz University for Health Sciences, Assuta Medical Center, Ariel University, Universidad de Cantabria, Marqués de Valdecilla University Hospital, Instituto de Investigación Marqués de Valdecilla
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: bronze
Funders: Amgen, Eli Lilly and Company, Pfizer, AstraZeneca, Memorial Sloan-Kettering Cancer Center, Jazz Pharmaceuticals, UroGen Pharma, Springworks Therapeutics, Eisai, Astellas Pharma, EUSA Pharma, Genentech, Loxo Oncology, Foundation Medicine, National Cancer Institute, Janssen Research and Development
OpenAlex ID: W4322757489