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
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: David B. Solit -- Source: Scopus
Citation Impact
MSK Authors
  1. David Solit
    720 Solit
  2. Marc Rosenblum
    407 Rosenblum
  3. Darren Richard Feldman
    304 Feldman
  4. Marc Ladanyi
    1262 Ladanyi
  5. Robert Soslow
    789 Soslow
  6. Agnes Viale
    241 Viale
  7. William P Tew
    221 Tew
  8. Nicholas D Socci
    240 Socci
  9. Michael Forman Berger
    686 Berger
  10. Neerav Shukla
    135 Shukla
  11. Manda E Wilson
    16 Wilson
  12. Eli Louis Diamond
    166 Diamond
  13. Ahmet Dogan
    386 Dogan
  14. Benjamin Heath Durham
    103 Durham
  15. Samuel Aaron Funt
    112 Funt
  16. Jesse   Galle
    16 Galle
  17. Andrew L Kung
    81 Kung
  18. Mariko   Yabe
    38 Yabe
  19. Dalicia Nicole Reales
    10 Reales
  20. Justin J Buthorn
    19 Buthorn
  21. Ying Liu
    71 Liu
  22. Tina M Alano
    7 Alano
  23. Bernadette Maher Wolff
    1 Wolff
  24. Amy E Webber
    1 Webber