Riccardo Orlandi1, Paolo Mendogni2, Mario Nosotti1,2, Annalisa Trama3, Monica Ganzinelli4, Giovanni Comacchio5, Giovanni Leuzzi6, Emanuele Voulaz7, Paolo Andrea Zucali8,9, Giulia Pasello10, Irene De Simone11, Francesca Galli11, Giovannella Palmieri12, Erica Pietroluongo13, Marcello Carlo Ambrogi14, Vittorio Aprile14, Lorenzo Rosso1,2; the Italian collaborative group for ThYmic MalignanciEs (TYME)
1Department of Thoracic Surgery, University of Milan, Milan, Italy;
2Thoracic Surgery and Lung Transplant Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy;
3Evaluative Epidemiology, Fondazione IRCCS-Italian National Cancer Institute, Milan, Italy;
4Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy;
5Thoracic Surgery Unit, Department of Cardiologic, Thoracic and Vascular Sciences, University Hospital, Padova, Italy;
6Division of Thoracic Surgery, IRCCS Istituto Nazionale dei Tumori Foundation, Milan, Italy;
7Division of Thoracic Surgery, Humanitas Clinical and Research Center - IRCCS, Milan, Italy;
8Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy;
9Department of Oncology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy;
10Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy;
11Mario Negri Institute for Pharmacological Research, IRCCS, Milan, Italy;
12University of Naples “Federico II”, Department of Clinical Medicine and Surgery, CRCTR Regional Rare Tumors Reference Center, Naples, Italy;
13Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy;
14Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
Correspondence to: Riccardo Orlandi, MD. Department of Thoracic Surgery, University of Milan, via Festa del Perdono, 7, Milan, 20122, Italy. Email: riccardo.orlandi@unimi.it.
Background: Tumor-node-metastasis (TNM) stage IVA thymic epithelial tumors (TETs) are rare and pose significant challenges due to limited and heterogeneous data. A major difficulty in managing stage IVA disease is the lack of clarity on the optimal treatment approach, particularly concerning the role of surgery, which remains controversial. This study aimed to evaluate clinical characteristics, pathological findings, and oncological outcomes in a consecutive cohort of surgically treated patients from the referring centers of the ThYmic MalignanciEs (TYME) Italian Network.
Methods: Patients with pathologically confirmed stage IVA TETs undergoing surgery were retrospectively reviewed from the TYME Network database. Demographic, clinical, and histopathological variables were analyzed, including prior cancer, autoimmune disease, Eastern Cooperative Oncology Group (ECOG) and American Society of Anesthesiologists (ASA) scores, histologic subtype, resection status, and use of perioperative treatments. Survival outcomes were estimated using Kaplan-Meier analysis, and predictors of recurrence-free survival (RFS) and overall survival (OS) were explored through univariable and multivariable methods.
Results: Fifty patients were enrolled. The median age was 51 years; 64% were male. All patients underwent surgery with curative intent; R0 resection was achieved in 73.3%. The most common histotypes were B2 (22%), B1 (20%), B3 (16%), and squamous thymic carcinoma (16%). Preoperative chemotherapy was administered to 45% of patients, postoperative radiotherapy to 42% of patients. Median OS was 122.9 months (Figure 1). There was no significant survival difference by resection margin (P=0.68) or preoperative chemotherapy (P=0.74). Median disease-free interval from the first surgery was 18 months (range, 1–181 months). R0 patients showed longer mean RFS (28.3 months) than R1-R2 (19.0 months), but the difference was not statistically significant. Histologic subtype was strongly associated with RFS (P=0.03). B1 thymoma had the longest RFS (61 months), significantly longer than thymic carcinoma (6.6 months, P=0.03). In multivariable analysis, histologic type and tumor volume were independent predictors of RFS (P<0.001 and P=0.03, respectively).
Conclusions: Surgical resection in TNM stage IVA TETs is feasible and can achieve long-term survival in selected patients within a multimodal treatment strategy. Histologic subtype is a key determinant of both recurrence risk and survival. These findings support surgery as a critical component of multimodal therapy, with histopathology and tumor volume guiding postoperative management and follow-up strategies.
Keywords: Thymoma; thymic carcinoma; stage IVA; surgery; multimodal treatment
