Session Item

Current guidelines on radiotherapy (RT) dose for thymic epithelial tumors (TET) based on old and small studies using 2D-RT with low levels of evidence IV-V (1). We aim to shed light on the optimal RT doses for TET patients treated with modern RT techniques through a systematic review of more recent literature.

We first designed and registered the protocol (PROSPERO ID: CRD42021241826) for review and followed PRISMA guidelines. A comprehensive search of 4 databases was conducted. The literature search included retrospective and prospective studies on humans affected by TETs undergoing external beam radiation with modern techniques such as IMRT/VMAT, SBRT, 3D-CRT, or proton therapy, published in English from 1990-2021. Inclusion criteria were information on RT dose-response, a sample size of ≥ 20 patients, follow-up time of ≥ 5 years, and treatment outcomes (overall survival, progression-free survival, toxicity). Duplicates, reviews and studies reporting only 2D-RT were excluded. Two researchers (AA, SP) independently screened and reviewed all citations, after an interrater-reliability-test (Cohen’s Kappa). A 3rd person (DR) provided final arbitration if consensus on inclusion could not be reached. Risk of bias assessment was done for the selected studies using the New Castle-Ottawa scale. AA and SP independently extracted all the data, and a narrative synthesis without meta-analysis of the collected data was carried out.

The online database search identified 966 citations, and 179 of these were selected for a full-text review (Fig. 1). Interrater reliability test based on 66 abstracts showed a very high agreement between the investigators (Cohen’s K = 0,91). Only two studies fulfilled all inclusion criteria. With a less stringent minimal follow-up time of 3 years, 3 additional studies could be included. These 5 studies with a total of 357 patients were synthesized according to stage, histology, and intervention (Table 1). Only 1 prospective study was found, including patients of all stages and histology (Fan X. et al, 2020) which showed a better OS and PFS with RT dose ≥60Gy using IMRT and concurrent chemotherapy. A retrospective study on postoperative RT (PORT) in stage II thymoma showed no significant results when PORT doses were compared (Chen et al, 2010). For stage III TET, 2 studies were found: for primary or definitive RT (dRT) an improved OS was found with a total dose of 54 Gy or higher (Fan C. et al, 2020), but not for PORT (Fan C et al, 2013). One study on salvage RT in recurrences showed a significantly better OS and PFS with ≥52 Gy compared to <52Gy (Yang et al, 2019).

With this systematic review, we could not identify the optimal RT dose for postoperative, nor primary RT in the era of modern RT because only a few small studies with heterogeneity regarding WHO subtype, stage and treatment could be identified. The question regarding the optimal RT dose to deliver for TETs is left unanswered and warrants further research.