CRES3T: A single-arm confirmatory trial of S-1 plus cisplatin with concurrent radical-dose radiotherapy followed by surgery for superior sulcus tumors

Lung Cancer. 2025 Apr:202:108506. doi: 10.1016/j.lungcan.2025.108506. Epub 2025 Mar 19.

Abstract

Purpose: This multicenter single-arm confirmatory trial (CRES3T) investigated the efficacy and safety of S-1 + cisplatin and concurrent radical-dose radiotherapy followed by surgery in patients with a superior sulcus tumor.

Methods: Patients received induction therapy comprising three cycles of S-1 + cisplatin with concurrent radiotherapy (66 Gy in 33 fractions) followed by surgery. S-1 was administered orally at 40 mg/m2 twice/day on days 1-14, with an intravenous infusion of cisplatin (60 mg/m2) on day 1. The primary endpoint was the 3-year overall survival rate; key secondary endpoints included progression-free survival rate, objective response rate, pathological complete response rate, and toxicity.

Results: Sixty-one patients with a superior sulcus non-small cell lung cancer received induction therapy. Radiological tumor invasion sites were the chest wall (n = 57), subclavian artery (n = 18), and subclavian vein (n = 10). Forty-nine patients underwent a lobectomy and combined resection of the involved structures. The objective and pathological complete response rates were 42 % (95 % confidence interval: 29-54 %) and 33 % (95 % confidence interval: 20-46 %), respectively. The 3-year overall survival and progression-free survival rates were 73.2 % (95 % confidence interval: 60.1-82.7 %) and 53.3 % (95 % confidence interval: 40.0-65.0 %), respectively. The patterns of first tumor relapse were locoregional only in one, distant metastasis only in 18, and both in four patients. Two pneumonia cases during induction therapy and one cardiac-arrest case on postoperative day 3 resulted in death.

Conclusions: Induction therapy using S-1 + cisplatin and concurrent radical-dose radiotherapy followed by surgery maximized local control and improved overall survival without impairing safety, potentially representing a new standard treatment.

Keywords: Induction-concurrent chemoradiotherapy; Radical-dose radiotherapy; S-1+cisplatin; Superior sulcus tumor; Surgery.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / mortality
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Carcinoma, Non-Small-Cell Lung* / therapy
  • Chemoradiotherapy*
  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • Drug Combinations
  • Female
  • Humans
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / pathology
  • Lung Neoplasms* / therapy
  • Male
  • Middle Aged
  • Oxonic Acid / administration & dosage
  • Pneumonectomy
  • Tegafur / administration & dosage
  • Treatment Outcome

Substances

  • Cisplatin
  • Drug Combinations
  • Oxonic Acid
  • S 1 (combination)
  • Tegafur