@article{10902/31316,
year = {2023},
url = {https://hdl.handle.net/10902/31316},
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},
organization = {Y.L. has received research funding from AstraZeneca, GSK, and REPARE Therapeutics unrelated to this work. C.A. has received consulting fees from Eisai, Merk, Roche/Genentech, Abbvie, AstraZeneca and Repare Therapeutics and clinical trial funding from AstraZeneca. M.Y. has served as a consultant for Janssen Research and Development. O.A.-W. has served as a consultant for H3B Biomedicine, Foundation Medicine Inc, Merck, and Janssen, Loxo Oncology/Lilly and is on the Scientific Advisory Board of Envisagenics Inc and Harmonic Discovery Inc.; O.A.-W. has received prior research funding from H3B Biomedicine, Loxo Oncology/Lilly, and Nurix Therapeutics unrelated to the current manuscript. M.B. has served as a consultant for Eli Lilly, PetDx and received research funding from Grail. J.G.B has served as a consultant for Jazz Pharmaceuticals, was an uncompensated consultant on a DSMB for Springworks, Merck and Pfizer and served on pediatric advisory boards for BMS and Eisai. She receives institutional research support (but no salary support) for clinical trials from Roche, Merck, Amgen, Lilly, BMS, Eisai, Novartis, Loxo-oncology, Cellectar and Bayer. S.A.F. has received research support from AstraZeneca, Genentech/Roche, and Decibel Therapeutics is a consultant/advisory board member for Merck and BioNTech, and owns stock in Urogen, Allogene Therapeutics, Neogene Therapeutics, Kronos Bio, ByHeart, 76Bio, Vida Ventures, Inconovir, and Doximity. A.D. served as a consultant for Incyte, EUSA Pharma, Loxo Oncology and receives research support from Roche and Takeda. R.A.S. was paid annually for serving as assistant editor for one of the USCAP society journals. H.A-A. has served as a consultant for AstraZeneca and Paige.AI. D.R.F. has received research funding from Telix Pharmaceuticals, Decibel Therapeutics, Astellas, Royalties from Up-to-Date, and has served as a consultant for BioNTech. E.M.V. has served as an advisor/Consultant to Tango Therapeutics, Genome Medical, Genomic Life, Enara Bio, Manifold Bio, Monte Rosa, Novartis Institute for Biomedical Research, Riva Therapeutics, Serinus Bio, has received research support from Novartis, BMS, Sanofi, and has equity interests in Tango Therapeutics, Genome Medical, Genomic Life, Syapse, Enara Bio, Manifold Bio, Microsoft, Monte Rosa, Riva Therapeutics, Serinus Bio. E.L.D. discloses unpaid editorial support from Pfizer, Inc, and paid advisory board membership with Day One Biopharmaceuticals and Springworks Therapeutics. D.B.S. has served as a consultant for/received honorarium from Pfizer, Loxo Oncology/Lilly, Vividion Therapeutics, Scorpion Therapeutics, FORE Therapeutics, Fog Pharma, Elsie Biotechnologies, and BridgeBio. The remaining authors declare no potential conflicts of interest.},
publisher = {American Association for Cancer Research},
publisher = {Clinical cancer research, 2023, 29(13), 2445-2455},
title = {Overcoming barriers to tumor genomic profiling through direct-to-patient outreach},
author = {Doe-Tetteh, Seyram A. and Camp, Sabrina Y. and Reales, Dalicia and Crowdis, Jett and Noronah, Anne Marie and Wolff, Bernadette and Alano, Tina and Galle, Jesse and Selcukle, S. Duygu and Viale, Agnes and Socci, Nicholas D. and Liu, Ying L. and Tew, William P. and Aghajanian, Carol and Ladanyi, Marc and Xiao He, Meng and Riancho Moral, José Antonio and Hernández Hernández, José Luis and González Vela, María del Carmen and AlDubayan, Saud H.},
}