Hyperthermic intrathoracic chemotherapy (HITOC) offers a strategy to eliminate microscopic residual disease after surgical resection. Especially it is investigated to improve long-term survival in thymic epithelial tumors with pleural dissemination or recurrence. A prospective, multicenter, randomized phase III clinical trial (CHOICE-2) is conducted to compare the efficacy and safety of surgery combined with HITOC versus surgery alone. The HITOC regimen involves intrathoracic perfusion with doxorubicin on postoperative day 1 and cisplatin on postoperative day 2.
Thymic epithelial tumors (TETs) frequently manifest with or recur as pleural dissemination (Stage IVa), presenting a significant clinical challenge. Although cytoreductive surgery is the cornerstone of treatment, achieving complete elimination of microscopic residual disease remains difficult, often leading to subsequent recurrence. Hyperthermic intrathoracic chemotherapy (HITOC) has emerged as a promising adjuvant strategy to control local disease by combining the cytotoxic effects of chemotherapy with hyperthermia to eradicate microscopic residuals. Building on the favorable safety and efficacy results from the Phase II CHOICE study, the CHOICE-2 study is a prospective, multicenter, randomized, phase III clinical trial designed to compare surgery combined with HITOC versus surgery alone. A total of 202 eligible participants with pleural dissemination or pleural recurrence of TETs will be randomized in a 1:1 ratio into two arms. Participants in the experimental arm will undergo lung-preserving cytoreductive surgery (pleurectomy/decortication or extended pleurectomy/decortication) followed by HITOC. The HITOC regimen involves intrathoracic perfusion with doxorubicin (25 mg/m²) on postoperative day 1 and cisplatin (50 mg/m²) on postoperative day 2, utilizing a perfusion system heated to 43°C for 60 minutes. Participants in the control arm will receive the same standard surgical resection without HITOC. The primary objective is to evaluate the 3-year progression-free survival (PFS) rate. Secondary endpoints include overall survival (OS), myasthenia gravis (MG) remission rates according to MGFA criteria, and the incidence of perioperative complications.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Patients undergo lung-preserving cytoreductive surgery, including pleurectomy/decortication (P/D) or extended pleurectomy/decortication (eP/D), via video-assisted thoracoscopic surgery (VATS) or thoracotomy. The goal is to achieve macroscopic complete resection of all visible pleural nodules and involved structures (e.g., pericardium, diaphragm). Extrapleural pneumonectomy (EPP) is excluded from the surgical strategy.
Patients undergo the same cytoreductive surgery (P/D or eP/D) as the control group. Following surgery, patients receive hyperthermic intrathoracic chemotherapy (HITOC) using a hyperthermic perfusion system heated to 43°C. The regimen consists of intrathoracic perfusion with doxorubicin (25 mg/m²) on postoperative day 1 (POD 1), followed by intrathoracic perfusion with cisplatin (50 mg/m²) on postoperative day 2 (POD 2).
Shanghai Zhongshan Hospital
Shanghai, China
3-year progression-free survival (PFS)
Time frame: The 3-year PFS is defined as the proportion of patients who are alive and have not experienced disease progression at 3 years after surgery.
3-year overall survival (OS)
Time frame: The 3-year OS is defined as the proportion of patients who are alive at 3 years after surgery, regardless of disease status or cause of death.
Myasthenia gravis remission rate (MGFA criteria)
The proportion of participants with myasthenia gravis (MG) achieving "Overall Remission" assessed according to the Myasthenia Gravis Foundation of America (MGFA) Post-Intervention Status Classification. As per the study protocol, overall remission is defined as the sum of patients achieving complete stable remission (CSR), pharmacologic remission (PR), or minimal manifestation status (MMS).
Time frame: The MG remission rate is calculated at the last follow-up in the three years after surgery.
Grade ≥3 complications (Clavien-Dindo, 5th ed.)
The complication rate was calculated at 1 month after surgery
Time frame: 1 month postoperatively
Quality of life (EORTC QLQ-C30) at 1 month
Time frame: 1 month postoperatively
Quality of life (EORTC QLQ-C30) at 3 months
Time frame: 3 months postoperatively
Quality of life (EORTC QLQ-C30) at 6 months
Time frame: 6 months postoperatively
Perioperative myasthenic crisis incidence
Postoperative Myasthenic Crisis (POMC) is defined as respiratory failure caused by myasthenia gravis (MG) requiring immediate intubation and total postoperative ventilatory support for more than 24 hours or requiring re-intubation and ventilatory support within 30 days after extubation. The POMC rate was calculated at 1 month after surgery.
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Masking
SINGLE
Enrollment
202
Time frame: 1 month postoperatively