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Exploratory analysis of gene aberrations and chemotherapy response: findings from a real-world database in Japan.

Naoya Ishibashi1,2, Takashi Kamatani1,3, Satoru Aoyama1

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Genetic alterations alone do not predict chemotherapy response better than tumor origin. Combining genetic and organ data may improve predictions, but requires further validation.

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Area of Science:

  • Oncology
  • Genomics
  • Pharmacology

Background:

  • Chemotherapy selection traditionally relies on tumor tissue of origin.
  • Genetic alterations drive tumor behavior, prompting investigation into their predictive value for chemotherapy response.
  • The study explores whether mutations can better predict treatment outcomes than tumor origin.

Purpose of the Study:

  • To evaluate the predictive power of genetic alterations versus tumor origin for chemotherapy response.
  • To assess the efficacy of combining genomic and organ-based data for predicting treatment outcomes.
  • To investigate gene-organ interactions in predicting objective response rate (ORR) and time to next treatment (TNT).

Main Methods:

  • Retrospective analysis of 15,474 Japanese patients with solid tumors.
  • Comprehensive genomic profiling (CGP) and assessment of genetic alterations.
  • Evaluation of tumor origin, gene mutations, ORR, and TNT across five chemotherapy classes.

Main Results:

  • Genomic alteration data alone did not outperform organ-based models in predicting response (AUC 0.575 vs. 0.604).
  • A combined gene-organ model improved prediction (AUC 0.618, P < 0.01).
  • Specific gene-organ interactions, like APC-mutated colorectal cancer with platinum-based drugs, showed improved ORR and prolonged TNT.

Conclusions:

  • Genetic alterations alone are insufficient to outperform tumor origin in predicting chemotherapy response.
  • Integrating both genetic and organ-based information may enhance predictive accuracy for chemotherapy.
  • Prospective validation is necessary before clinical application of these findings.