Addressing the knowledge gap in the genomic landscape and tailored therapeutic approaches to adolescent and young adult cancers

ESMO Open. 2024 Aug;9(8):103659. doi: 10.1016/j.esmoop.2024.103659. Epub 2024 Aug 12.

Abstract

Background: Adolescents and young adults (AYAs) represent a small proportion of patients with cancer. The genomic profiles of AYA patients with cancer are not well-studied, and outcomes of genome-matched therapies remain largely unknown.

Patients and methods: We investigated differences between Japanese AYA and older adult (OA) patients in genomic alterations, therapeutic evidence levels, and genome-matched therapy usage by cancer type. We also assessed treatment outcomes.

Results: AYA patients accounted for 8.3% of 876 cases. Microsatellite instability-high and/or tumor mutation burden was less common in AYA patients (1.4% versus 7.7% in OA; P = 0.05). However, BRCA1 alterations were more common in AYA patients with breast cancer (27.3% versus 1.7% in OA; P = 0.01), as were MYC alterations in AYA patients with colorectal cancer (23.5% versus 5.8% in OA; P = 0.02) and sarcoma (31.3% versus 3.4% in OA; P = 0.01). Genome-matched therapy use was similar between groups, with overall survival tending to improve in both. However, in AYA patients, the small number of patients prevented statistical significance. Comprehensive genomic profiling-guided genome-matched therapy yielded encouraging results, with progression-free survival of 9.0 months in AYA versus 3.7 months in OA patients (P = 0.59).

Conclusion: Our study suggests that tailored therapeutic approaches can benefit cancer patients regardless of age.

Keywords: adolescent; genome-matched therapy; genomic profiling; older adult; treatment outcome; young adult.

MeSH terms

  • Adolescent
  • Adult
  • Female
  • Genomics* / methods
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Neoplasms* / genetics
  • Neoplasms* / therapy
  • Precision Medicine / methods
  • Young Adult