Cytoreductive surgery followed by hyperthermic intrathoracic chemotherapy for the treatment of thymic epithelial malignancies with pleural spread or recurrence.

Shuai Wang Fudan University Zhongshan Hospital, Shanghai, China info_outline Shuai Wang, Jiahao Jiang, Xinyu , Fei Liang, Yuansheng Zheng, Yongqiang Ao, Jianyong Ding

Authors Shuai Wang Fudan University Zhongshan Hospital, Shanghai, China info_outline Shuai Wang, Jiahao Jiang, Xinyu , Fei Liang, Yuansheng Zheng, Yongqiang Ao, Jianyong Ding Organizations Fudan University Zhongshan Hospital, Shanghai, China, Zhongshan Hospital, Fudan University, Shanghai, China, Fudan University, Shanghai, China, Department of Statistics, Zhongshan Hospital Fudan University, Shanghai, China Abstract Disclosures Research Funding Zhongshan Hospital, Fudan University Background: The purpose of this phase II study was to evaluate perioperative results and short-term oncological outcomes of cytoreductive surgery and hyperthermic intrathoracic chemotherapy (S-HITOC) for thymic epithelial malignancies (TETs) with pleural spread or recurrence. Methods: In this open, single-arm, prospective trial, 43 consecutive patients were recruited and treated by surgical cytoreduction (Day 0) followed by HITOC with 25mg/m 2 of doxorubicin (Day 1) and 50mg/m 2 of cisplatin (Day 2). HITOC was performed over a period of 60 minutes with a flow rate of 400 to 600 mL/min at an inflow temperature of 43°C. This study was registered with ClinicalTrials.gov (NCT05446935). Results: There were 22 women and 21 men with a median age of 55 years. Twelve patients (27.9%) were presented with myasthenia gravis (MG). Predominately, 34 cases (79.1%) were TETs with distant pleural recurrence and 9 cases (20.9%) were TETs with de novo pleural spread. Cytoreduction surgery was performed via pleurectomy/decortication (P/D) alone (5/43, 11.6% ) or extended P/D (eP/D) (38/43, 88.4%). These resection procedures resulted in 21 cases (48.8%) of complete cytoreductive surgery without residual visible disease, 6 cases (14.0%) of optimal cytoreductive surgery with residual tumors measuring no more than 10 mm or 16 cases (37.2%) of incomplete cytoreductive surgery with residual lesions measuring more than 10 mm in diameter. The median length of postoperative hospital stay were 5.0 days. Eight patients (18.6%) had grade 3-4 treatment-related complications, including 2 cases of atelectasis, 2 cases of hydrothorax, 1 case of pneumonia, 1 case of hemothorax, 1 case of atrial fibrillation, and 1 case of chest pain. Patients had moderate level of pain on Day 3 [mean visual analog pain scale (VAS) score = 5.5]. However, the VAS scores decreased significantly on the Day 5 (mean VAS score = 2.8). The health-related quality-of-life (QoL) outcomes had continue improvement during the follow-up period, with the mean QoL scores of 59.0 at Day 3, 70.2 at Day 33, and 77.6 at Day 63, according to the EORTC QLQ-C30. The 90-day mortality rate was 0%. At median follow-up of 11 (3-37) months, 39 patients (90.7%) were free of tumor progression. The 1-, 2-, and 3-year PFS rate was 96.6, 82.8, and 70.9%. While two cases died, as one patient developed multiple organ failure and one case with pulmonary fungal infection. The 1-, 2-, and 3-year OS rate was 100.0, 100.0, and 85.7%. Importantly, overall remission rate of MG was 100%, with complete stable remission rate of 25.0%, pharmacological remission rate of 41.7% and minimal manifestation status rate of 33.3%. Conclusions: S-HITOC is a safe and feasible procedure with acceptable complication rate. Early clinical outcomes confirm S-HITOC offers encouraging oncological benefits for TETs and satisfactory control of MG. Clinical trial information: NCT05446935.