Implication of S-1 biomarkers on aging and prognosis in elderly patients with lung cancer treated by adjuvant S-1 chemotherapy: Accompanying results of the Setouchi Lung Cancer Group Study 1201

Soh, J.; Yamamoto, H.; Okumura, N.; Suzuki, H.; Nakata, M.; Fujiwara, T.; Gemba, K.; Sano, I.; Fujinaga, T.; Kataoka, M.; Terasaki, Y.; Fujimoto, N.; Kataoka, K.; Kosaka, S.; Yamashita, M.; Inokawa, H.; Inoue, M.; Nakamura, H.; Yamashita, Y.; Takahashi, Y.; Torigoe, H.; Sato, H.; Tomida, S.; Hotta, K.; Yoshioka, H.; Morita, S.; Matsuo, K.; Sakamoto, J.; Date, H.; Toyooka, S.

doi:10.1101/2024.11.23.625024

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bioRxiv · 10.1101/2024.11.23.625024

Implication of S-1 biomarkers on aging and prognosis in elderly patients with lung cancer treated by adjuvant S-1 chemotherapy: Accompanying results of the Setouchi Lung Cancer Group Study 1201

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Abstract

BACKGROUNDSThe management of elderly patients presents several challenges due to age-related declines; however recent recommendations advocate for age not being the sole determinant for adjuvant treatment decisions in patients with non-small cell lung cancer (NSCLC). Aging may alter expression levels of 5-fluorouracil (5-FU) biomarkers. METHODSExpression changes with aging were explored using The Cancer Genome Atlas (TCGA) database. 5-FU-related biomarker expressions, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase, epidermal growth factor receptor (EGFR), and excision repair cross-complementation group-1 (ERCC1), were assessed by the quantitative reverse-transcription PCR assays in 89 NSCLCs elderly patients ([≥] 75 years old) receiving adjuvant S-1, an oral fluoropyrimidine agent, therapy in a SLCG1201 trial. RESULTS: TCGA database analysis (n=955) indicated decreased TS expression with aging, particularly in those 75 or older. In the SCLG1201 trial, univariate analysis revealed that high EGFR and low TS expressions correlated with favorable recurrence-free survival (RFS)(p=0.0264) and overall survival (OS)(p=0.0365), respectively. Multivariable analysis confirmed pathological stage as an independent prognostic factor for both RFS and OS (p=0.0052 and 0.0352, respectively). EGFR mutant tumors (n=27) showed significantly higher DPD (p=0.0066) and EGFR (p<0.0001) expressions, and lower TS(p=0.0125) and ERCC1(p=0.0015) expressions. CONCLUSIONDespite pathological stage being an independent prognostic factor, high EGFR and low TS expressions may predict better clinical outcomes in elderly NSCLC patients using adjuvant S-1. The age-related decrease in TS expression supports the potential benefit of 5-FU-based therapy in them compared to younger patients. Further research is warranted to validate these clinical implications.

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Soh, J., Yamamoto, H., Okumura, N., Suzuki, H., Nakata, M., Fujiwara, T., Gemba, K., Sano, I., Fujinaga, T., Kataoka, M., Terasaki, Y., Fujimoto, N., Kataoka, K., Kosaka, S., Yamashita, M., Inokawa, H., Inoue, M., Nakamura, H., Yamashita, Y., Takahashi, Y., Torigoe, H., Sato, H., Tomida, S., Hotta, K., Yoshioka, H., Morita, S., Matsuo, K., Sakamoto, J., Date, H., Toyooka, S.. 2024-11-25. Implication of S-1 biomarkers on aging and prognosis in elderly patients with lung cancer treated by adjuvant S-1 chemotherapy: Accompanying results of the Setouchi Lung Cancer Group Study 1201. https://doi.org/10.1101/2024.11.23.625024

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