Dataset Information

Induction Therapy Followed by Surgery for Unresectable Thymic Epithelial Tumours.

ABSTRACT:

Background and objectives

The treatment of unresectable thymic epithelial tumours (TETs) remains controversial. Here, we present the efficacy and safety of induction therapy followed by surgery for unresectable TET.

Methods

Eighty-one patients with unresectable TETs treated with induction therapy followed by surgery were selected from a retrospective review of consecutive TETs from January 2005 to January 2021. Clinicopathological data were analyzed to assess tumour responses, resectability, adverse events, progression-free survival (PFS) and overall survival (OS).

Results

Induction therapy produced a major tumour response rate of 69.1%, a tumour response grade (TRG) 1-3 rate of 84.0% and an R0 resection rate of 74.1%. The most common toxic effects were all-grade neutropenia (35.8%) and anaemia (34.6%). The 10-year OS and PFS rates were 45.7% and 35.2%. Multivariate analysis showed that ypTNM stage, ypMasaoka stage, complete resection, and TRG were significant independent prognostic factors. Exploratory research revealed that different induction modalities and downstaging of T, N, M, TNM, or Masaoka classifications did not significantly alter the pooled hazard ratio for survival.

Conclusions

Induction therapy followed by surgery is well tolerated in patients with unresectable TETs, with encouraging R0 resection rates. Multimodality management provides good control of tumors for unresectable TET patients.

SUBMITTER: Wang S

PROVIDER: S-EPMC8766658 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Simple Summary The biology of thymic epithelial tumours (TETs), including thymomas and thymic carcinomas, and particularly the extent of molecular dysregulation, is poorly understood. Through next-generation sequencing of 15 genes implicated in common solid tumours in 53 TETs, we found a larger number of single nucleotide variants (SNVs) in thymic carcinomas than thymomas. About 30% of thymic carcinomas had at least one somatic pathogenic gene variant in TP53, ERBB2, KIT, or KRAS, whereas variants of uncertain clinical significance in KIT, ERBB2, and FOXL2 were found exclusively in thymomas. The presence of somatic pathogenic variants was non-significantly associated with shorter disease-free survival in thymic carcinoma patients. No somatic pathogenic or likely pathogenic SNV was found in thymomas. Importantly, we also evaluated germline SNVs, adding to the number of known genetic alterations in TETs and thereby enhancing our molecular understanding of these neoplasms. Abstract A better understanding of the molecular pathogenesis of thymic epithelial tumours (TETs) could revolutionise their treatment. We evaluated thymomas and thymic carcinomas by next-generation sequencing (NGS) of somatic or germline single nucleotide variants (SNVs) in genes commonly mutated in solid tumours. In total, 19 thymomas and 34 thymic carcinomas were analysed for nonsynonymous SNVs in 15 genes by targeted NGS (reference genome: hg19/GRCh37). Ten SNVs in TP53 (G154V, R158P, L194H, R267fs, R273C, R306 *, Q317 *), ERBB2 (V773M), KIT (L576P), and KRAS (Q61L) considered somatic and pathogenic/likely pathogenic were detected in 10 of 34 (29.4%) thymic carcinomas. No somatic SNVs confirmed as pathogenic/likely pathogenic were found in thymomas. Rare SNVs of uncertain or unknown functional and clinical significance, to our knowledge not reported previously in TETs, were found in ERBB2 (S703R), KIT (I690V), and FOXL2 (P157S) in 3 of 19 (16%) thymomas. The most frequent germline SNVs were TP53 P72R (94% TETs), ERBB2 I655V (40% TETs), and KIT M541L (9% TETs). No significant difference in median disease-free survival (DFS) was found between thymic carcinoma patients with and without pathogenic SNVs (p = 0.190); however, a trend toward a longer DFS was observed in the latter (16.0 vs. 30.0 months, respectively). In summary, NGS analysis of TETs revealed several SNVs in genes related to the p53, AKT, MAPK, and K-Ras signalling pathways. Thymic carcinomas showed greater genetic dysregulation than thymomas. The germline and rare SNVs of uncertain clinical significance reported in this study add to the number of known genetic alterations in TETs, thus extending our molecular understanding of these neoplasms. Druggable KIT alterations in thymic carcinomas have potential as therapeutic targets.