Postoperative radiotherapy for thymic epithelial tumors: a narrative review.

Background and Objective: Thymic epithelial tumors (TETs), including thymomas and thymic carcinomas, are rare mediastinal tumors. Surgical resection is the treatment strategy for resectable TETs, and postoperative radiotherapy (PORT) is administered to improve local control in patients with a high risk of recurrence. The rarity of TETs has led to a lack of randomized controlled trials, and the current indications for PORT rely largely on retrospective studies. This review analyzes the literature on TETs, highlighting PORT, to guide current research and future investigations. Methods: Studies that focused on TETs, addressed topics on PORT, and had English abstracts accessible online were eligible for inclusion in our review. We excluded case reports or review articles, articles written in languages other than English, articles published >30 years ago, and articles concerning thymic neuroendocrine tumors. Key Content and Findings: Masaoka or Masaoka-Koga staging, World Health Organization (WHO) histological subtype, and resection status indicate PORT in resected TETs. Current literature suggests that PORT does not improve overall survival in stage I-IIA TETs, with inconsistent results for stage IIB-III TETs. Patients with a higher risk, such as carcinomas or WHO type B, might benefit from PORT if they do not develop distant metastasis. Determining which patients will benefit most from PORT requires further investigation. For recurrent TETs, the significance of applying PORT is unclear because available data are limited. Given the long-term survival of TETs, late toxicities, including radiation pneumonitis, radiation-induced cardiotoxicities, and secondary malignancies, must be addressed. Proton beam radiotherapy might reduce toxicities by sparing organs at risk compared to conventional photon beam radiotherapy. The use of high-precision radiation therapy, along with emerging immunotherapy, targeted therapy, and minimally invasive surgery, could improve TET outcomes. Conclusions: This review consolidates the literature on PORT for TETs, factoring in the Masaoka-Koga staging, WHO histological subtypes, and resection status. Varying results regarding PORT efficacy have led to an undefined strategy for stage IIB-III TETs. Although advanced radiotherapy techniques promise to reduce radiation-induced toxicities, further research is needed to investigate the efficacy of PORT and combination therapy.

The role of induction therapy for thymic malignancies: a narrative review.

Advanced thymic epithelial tumors pose a clinical dilemma for surgeons and medical oncologists. Given the prognostic importance of obtaining a complete resection, interventions that improve resectability may have profound implications. The documented chemosensitivity and radiosensitivity of thymic tumors present an opportunity to use these therapies in the neoadjuvant setting to reduce tumor burden and improve the likelihood of achieving a complete resection. The current evidence available is limited to institutional case-series, large retrospective multi-institutional databases, and phase II clinical trials. The primary objective of considering induction therapy should be facilitating a complete resection; other endpoints such as down-staging or pathologic response have not been shown to result in meaningful improvements in long-term outcomes. There are certain high-risk tumor characteristics that may aid clinicians in appropriately selecting patients for induction therapy. The selection of candidates for induction therapy should take place in a multidisciplinary tumor board including medical oncologist, surgeon, and radiation oncologist with experience in managing advanced thymic malignancies. Without randomized controlled trials, it is unlikely the thymic medical community will arrive at a consensus on the utility of induction therapy. This review will summarize the existing literature and provide insight into the role of induction therapy for advanced thymic malignancies.

Molecular genetic alterations in egfr CA-SSR-1 microsatellite and egfr copy number changes are associated with aggressiveness in thymoma.

BACKGROUND: The key role of egfr in thymoma pathogenesis has been questioned following the failure in identifying recurrent genetic alterations of egfr coding sequences and relevant egfr amplification rate. We investigated the role of the non-coding egfr CA simple sequence repeat 1 (CA-SSR-1) in a thymoma case series. METHODS: We used sequencing and egfr-fluorescence in situ hybridization (FISH) to genotype 43 thymomas; (I) for polymorphisms and somatic loss of heterozygosity of the non-coding egfr CA-SSR-1 microsatellite and (II) for egfr gene copy number changes. RESULTS: We found two prevalent CA-SSR-1 genotypes: a homozygous 16 CA repeat and a heterozygous genotype, bearing alleles with 16 and 20 CA repeats. The average combined allele length was correlated with tumor subtype: shorter sequences were significantly associated with the more aggressive WHO thymoma subtype group including B2/B3, B3 and B3/C histotypes. Four out of 29 informative cases analysed for somatic CA-SSR-1 loss of heterozygosity showed allelic imbalance (AI), 3/4 with loss of the longer allele. By egfr-FISH analysis, 9 out of 33 cases were FISH positive. Moreover, the two integrated techniques demonstrated that 3 out of 4 CA-SSR-1-AI positive cases with short allele relative prevalence showed significantly low or high chromosome 7 "polysomy"/increased gene copy number by egfr-FISH. CONCLUSIONS: Our molecular and genetic and follow up data indicated that CA-SSR-1-allelic imbalance with short allele relative prevalence significantly correlated with EGFR 3+ immunohistochemical score, increased egfr Gene Copy Number, advanced stage and with relapsing/metastatic behaviour in thymomas.

Clinicopathological analysis of 241 thymic epithelial tumors-experience in the Shanghai Chest Hospital from 1997-2004.

BACKGROUND: To assess the correlation of WHO histological classification of thymomas and thymic carcinomas (TCs) with prognosis in recently treated patient cohort compared to a historical one from a single institution. METHODS: Retrospective review of clinical charts and histological sections of 241 patients treated during 1997-2004. Univariate and multivariate analysis of associations between risk factors including gender, age, tumor size, myasthenia gravis, WHO histological subtype, Masaoka stage, resection status, (neo-)adjuvant therapies, and survival. RESULTS: The 5-year overall survival (OS) of A, AB, B1, B2, B3 thymomas and TCs patients was 100%, 100%, 94%, 80%, 94% and 45%. Five-year progression-free survival (PFS) was 100%, 96%, 78%, 80%, 78% and 39%, respectively. The 5-year OS of patients with Masaoka stage I, II, III and IV thymomas and TCs was 96%, 89%, 59% and 50%. (Neo-)adjuvant therapies were administered more often than in the historical cohort. Tumor-related death mainly occurred in patients with stage III, IV and B2, B3 thymomas and TCs. By univariate analysis, gender, tumor size, myasthenia gravis (MG) status, histotype, Masaoka stage, resection status and treatment were associated with OS. By multivariate analysis, histological subtype, Masaoka stage, and (neo-)adjuvant therapy were revealed as independent prognostic indicators. CONCLUSIONS: WHO histological subtype, Masaoka stage and (neo-)adjuvant treatment have remained independent determinants of OS in patients with thymomas and TCs. Compared with the historical cohort during 1969-1996, prognosis of patients with B2, B3 thymomas has improved, which may be partly due to the increased use of adjuvant therapies. Prognosis of patients with TCs remained unsatisfactory, suggesting that neoadjuvant treatment should be tested to improve survival.