Cytoreductive surgery followed by hyperthermic intrathoracic chemotherapy for the treatment of thymic epithelial malignancies with pleural spread or recurrence.
Authors: Wang Shuai , Jiang Jiahao , Xinyu Sr.  , Liang Fei , Zheng Yuansheng , Ao Yongqiang , Ding Jianyong 
Published: June 2024

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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/m2 of doxorubicin (Day 1) and 50mg/m2 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 .