Giovanni Leuzzi1, Federica Sabia1, Claudia Proto2, Giuseppe Lo Russo2, Monica Ganzinelli2, Alessandra Fabbri3, Matteo Perrino4, Nadia Cordua4, Alessandro Bertocchi5, Antonio Federico5, Paolo Andrea Zucali5,6, Marco Lucchi7, Marcello Carlo Ambrogi7, Vittorio Aprile7, Paolo Mendogni8, Fabiana Letizia Cecere9, Giovanni Comacchio10, Marianna Tortora11, Marzia Di Pietro Paolo12, Piergiorgio Solli1
1Division of Thoracic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;
2Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy;
32nd Pathology Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 4Department of Oncology, IRCCS Humanitas Research Hospital, Rozzano-Milan, Italy;
5Department of Biomedical Sciences, Humanitas University, Pieve Emanuele-Milan, Italy;
6Department of Oncology, IRCCS Humanitas Research Hospital, Rozzano-Milan, Italy;
7Division of Thoracic Surgery, Cardiac, Thoracic, and Vascular Department, University Hospital of Pisa, Pisa, Italy;
8Thoracic Surgery and Lung Transplant Unit, Foundation IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy;
9Medical Oncology 2 IRCCS Regina Elena National Cancer Institute, Rome, Italy; 10Thoracic Surgery Unit, Division of Surgery, University - Hospital of Padua, Padua, Italy;
11Rare Tumors Coordinating Center of Campania Region (CRCTR), Naples, Italy;
12Medical Oncology Unit, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi Ancona, Italy
Correspondence to: Giovanni Leuzzi, MD. Division of Thoracic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Giacomo Venezian 1, Milan, MI, 20133, Italy. Email: giovanni.leuzzi@istitutotumori.mi.it.
Background: Induction therapy (IT) in unresectable thymic tumours (UTTs) is an option to downstage the tumour and to obtain a complete resection as well as a better outcome. Which patients benefit from IT is still a matter of debate. This study aims to investigate treatment response (TR) after IT and potential prognostic factors among Italian patients with UTTs.
Methods: Clinicoradiological, histopathological, molecular, oncological and surgical features of 76 UTTs (clinical-TNM-stage II–IV) undergoing IT from 01/2002 to 12/2024 were retrospectively collected from the large multicentric database within the Italian collaborative group for ThYmic MalignanciEs (TYME).
Results: Mean age and male/female ratio were 52 years and 45/31, respectively. World Health Organization (WHO) histology was thymoma in 62 (82%), thymic carcinoma in 12 (16%) and neurondocrine neoplasia in 2 (3%) patients. According to 8th tumor-node-metastasis (TNM), pathological stage distribution was: stage I 6%, IIA 5%, IIB 8%, III 51%, IVA 19% and IVB 11%. The most administered IT regimen was cisplatin plus doxorubicin plus cyclophosphamide (PAC) in 61% of cases; adjuvant radiotherapy was performed in 68% of patients. According to Response Evaluation Criteria in Solid Tumours (RECIST) criteria, 67% patients achieved partial response (responders) and 33% stable/progressive disease (non-responders). Extended mediastinal resection with or without reconstruction was the most common surgical procedure (61%), through sternotomy (36%), thoracotomy (33%) and hemi-clamshell incision (19%). Radical R0 resection was achieved in 76% of cases. Median follow-up time from surgery was 2.8 years, with a 5-year overall survival (OS) and 5-year recurrence-free survival (RFS) of 92% and 31%, respectively (Figure 1). Compared to non-responders, responders had a more aggressive histology (24% vs. 16%), higher clinical TNM stage (84% vs. 71%), underwent mainly PAC scheme (65% vs. 37.5%) and achieved better radicality (78% vs. 68%). At multivariable analysis, physical status according to American Society of Anesthesiologists (ASA) score was the most important prognosticator of response after IT (“P=0.02”).
Conclusions: the TYME database analysis confirms a potential role for IT in UTTs. Due to high rate of non-responders, efforts should be made to investigate further multimodal treatments to improve response rate and resectability in this subset. Physical status according to ASA score seems a prognostic factor of TR in UTTs undergoing IT.
Keywords: Thymic tumors; induction therapy; response
