Cytoreductive Surgery With or Without Hyperthermic Intrathoracic Chemotherapy

Cytoreductive Surgery With or Without Hyperthermic Intrathoracic Chemotherapy for Thymic Epithelial Malignancies with Pleural Dissemination



Objective: Thymic epithelial tumors (TETs) with pleural dissemination represent therapeutic challenges. This study evaluated comparative effectiveness of surgery alone versus surgery combined with hyperthermic intrathoracic chemotherapy (Surg+HITCH) in TETs with pleural dissemination.
Methods: A total of 96 patients who histologically confirmed TETs with pleural dissemination were included from 2020 to 2024. Surgery with or without HITCH was performed using a standardized dual-agent protocol [doxorubicin (25 mg/m2) and cisplatin (50 mg/m2) perfused at 43°C for 60 minutes]. The pleural tumor burden was quantified by Pleural Tumor Index (PTI), which divides pleura into five anatomical zones: zone I (rib and chest wall), zone II (diaphragm), zone III (mediastinum), zone IV (lower pulmonary), and zone V (upper pulmonary). The largest lesion in each zone was scored from 0 to 3 (grade 0: no visible lesion; grade 1: lesion diameter <1.0 cm; grade 2: lesion diameter between 1.0–5.0 cm; grade 3: lesion diameter >5.0 cm or lesion fusion). The PTI score was the sum of scores from each zone. Perioperative, neurological, and oncological outcomes were compared between surgery-alone and Surg+HITCH groups.
Results: Complication rates were slightly higher in Surg+HITCH group (79.2% vs 68.8%) but were predominantly minor and not associated with increased ICU stays or mortality. The incidence of myasthenia gravis (MG) was comparable between two groups (35.4% vs. 39.6%). MG remission rate was markedly improved in Surg+HITCH group (94.7% vs 58.8%) compared to surgery-alone group. No significant difference was detected in 3-year overall survival (P=0.795) between two groups. The Surg+HITCH group had higher 3-year progression-free survival (PFS) (80.9% vs 48.0%; P = 0.022) and lower recurrence (10.4% vs 37.5%). PTI ≥10 was independently associated with worse PFS (HR, 1.44; 95% CI, 1.09–1.89, p=0.003). In Surg+HITCH cohort, multivariable analyses indicated histopathological type and PTI score were only two independent factors of PFS. Receiver operating characteristic curves identified PTI <10 was optimal candidates for Surg+HITCH.
Conclusion: Surg+HITCH improves tumor control and MG remission without increased operative mortality. The PTI offers a practical risk stratification tool to guide patient selection. These findings support the integration of Surg+HITCH into multidisciplinary management of TETs with pleural dissemination, especially in patients with low PTI.

Wang Shuai (1), Junkan Zhu (2), Jiahao Jiang (3), Xifei Jiang (4), Yuan Feng (5), Sikai Ge (6), Yuansheng Zheng (7), Xinyu Yang (8), Stephen Cassivi (9), Lijie Tan (10), Jianyong Ding (11), (1) Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, Shanghai, (2) Zhongshan Hospital, Fudan University, Shanghai, Shanghai, (3) Fudan University Zhongshan Hospital, Shanghai, Shanghai, (4) Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, NA, (5) Mayo Clinic (Rochester, MN), MN, (6) Xi'an Jiaotong-Liverpool University, Suzhou, NA, (7) Department of thoracic surgery, Zhongshan hospital, Fudan university, Shanghai, NA, (8) Shanghai Chest Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China, (9) Mayo Clinic College of Medicine and Science, Rochester, MN, (10) Zhong Shan Hospital, Shanghai, (11) Zhongshan hospital, Fudan university, Shanghai, NA