Synapse - Overcoming barriers to tumor genomic profiling through direct-to-patient outreach

Overcoming barriers to tumor genomic profiling through direct-to-patient outreach Journal Article

Authors:	Doe-Tetteh, S. A.; Camp, S. Y.; Reales, D.; Crowdis, J.; Noronha, A. M.; Wolff, B.; Alano, T.; Galle, J.; Selcuklu, S. D.; Viale, A.; Socci, N. D.; Liu, Y. L.; Tew, W. P.; Aghajanian, C.; Ladanyi, M.; He, M. X.; AlDubayan, S. H.; Mazor, R. D.; Shpilberg, O.; Hershkovitz-Rokah, O.; Riancho, J. A.; Hernandez, J. L.; Gonzalez-Vela, M. C.; Buthorn, J. J.; Wilson, M.; Webber, A. E.; Yabe, M.; Petrova-Drus, K.; Rosenblum, M.; Durham, B. H.; Abdel-Wahab, O.; Berger, M. F.; Donoghue, M. T. A.; Kung, A. L.; Glade Bender, J.; Shukla, N. N.; Funt, S. A.; Dogan, A.; Soslow, R. A.; Al-Ahmadie, H.; Feldman, D. R.; Van Allen, E. M.; Diamond, E. L.; Solit, D. B.
Article Title:	Overcoming barriers to tumor genomic profiling through direct-to-patient outreach
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. ©2023 American Association for Cancer Research.
Keywords:	genetics; mutation; ovarian neoplasms; ovary tumor; genomics; neoplasms, germ cell and embryonal; exome; humans; human; female; germ cell and embryonal neoplasms
Journal Title:	Clinical Cancer Research
Volume:	29
Issue:	13
ISSN:	1078-0432
Publisher:	American Association for Cancer Research
Date Published:	2023-07-01
Start Page:	2445
End Page:	2455
Language:	English
DOI:	10.1158/1078-0432.Ccr-22-3247
PUBMED:	36862133
PROVIDER:	scopus
PMCID:	PMC10330105
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85164246067&doi=10.1158%2f1078-0432.CCR-22-3247&partnerID=40&md5=e4fe366498737a5827d39cfcd12808f5
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: David B. Solit -- Source: Scopus