Abstract
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.