Thymic epithelial tumors express vascular endothelial growth factors and their receptors as potential targets of antiangiogenic therapy: A tissue micro array-based multicenter study

Lattanzio, Rossano; Sorda, Rossana La; Facciolo, Francesco; Sioletic, Stefano; Lauriola, Libero; Martucci, Robert; Gallo, Enzo; Palmieri, Giovannella; Evoli, Amelia; Alessandrini, Gabriele; Ruco, Luigi; Rendina, Erino Angelo; Truini, Mauro; Chiarle, Roberto; Barreca, Antonella; Pich, Achille; Ascani, Stefano; Remotti, Daniele; Tunesi, G; Granone, Pierluigi; Ratto, G. B.; Puma, Francesco; Pescarmona, Edoardo; Piantelli, Mauro; Marino, Mirella; Carlini, S.; Cerasoli, Virna; Corzani, Felicita; Melis, Enrico; M, Filippetti; Canalini, Paola; Palestro, Giorgio; Lalle, M; Ruffini, Enrico; Ceribelli, Anna; Rinaldi, Massimo

doi:10.1016/j.lungcan.2014.05.010

Cited by 34 publications

(24 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After progression on platinum-based therapy there are limited indications for second-line treatments like sunitinib and everolimus, with data mainly extrapolated from small, single-arm, phase II clinical trials, or retrospective observational studies. VEGF plays a key role in tumour angiogenesis and VEGFR2 and PDGFR-α are known to be activated in thymic carcinoma (10). The activity of sunitinib malate and Lenvatinib, two multi-targeted kinase inhibitors were tested in two phase 2 trials, in which 26 and 38% of patients with thymic carcinoma achieved a partial response, respectively (11,12).…”

Section: Introductionmentioning

confidence: 99%

Pembrolizumab in a Patient With Heavily Pre-Treated Squamous Cell Thymic Carcinoma and Cardiac Impairment: A Case Report and Literature Review

et al. 2020

View full text Add to dashboard Cite

Immunotherapy directed at the programmed cell death-1 receptor (PD-1) or its ligand PD-L1 has proven effective in solid malignancies such as melanoma, non-small cell lung cancer (NSCLC), urothelial cancer, renal cell carcinoma, and head and neck cancer. Compared with cytotoxic chemotherapy, radiotherapy, or molecular targeted agents, immunotherapy is an innovative strategy for treating malignancies, with durable clinical responses and manageable adverse events. Thymic carcinomas are extremely rare, constituting only 0.06% of all malignancies, are much more aggressive tumours than thymomas and have a worse prognosis. Nowadays, first line platinum-based chemotherapy for metastatic tumours are the cornerstone of treatment. However, the results of further therapeutic lines for metastatic or relapsed thymic carcinoma are unsatisfactory, with no regimen showing a consistent benefit. Moreover, the rarity of these tumours makes it difficult to carry out clinical trials. Herein we report a remarkable result of 1 year stable disease with good quality of life and no side effects obtained from the use of immunotherapy with pembrolizumab in a case of heavily pre-treated squamous cell thymic carcinoma and cardiac impairment. We also include a literature review of clinical trials on PD-1/PD-L1 inhibitors for the treatment of thymic epithelial cancers, taking a close look at cardiac toxicity.

show abstract

Section: Introductionmentioning

confidence: 99%

Pembrolizumab in a Patient With Heavily Pre-Treated Squamous Cell Thymic Carcinoma and Cardiac Impairment: A Case Report and Literature Review

et al. 2020

View full text Add to dashboard Cite

show abstract

“…80,81 However, angiogenesis is a relevant pathway in the pathogenesis of thymic tumors. VEGF-A, VEGF-C, VEGF-D, and their receptors VEGFR-1, VEGFR-2, and VEGFR-3 are overexpressed in high-risk thymoma and thymic carcinoma 82 and is correlated with tumor aggressiveness.- 83 Anti-angiogenic agents have then been evaluated in combination with other agents. Sunitinib (oral tyrosine kinase inhibitor of VEGFRs, KIT, and PDGFRs) showed some activity in the treatment of TETs irrespective of histological subtype and presence of KIT mutations with median progressionfree survival at 3.7 months and overall survival at 15.4 months.…”

Section: Targeted Therapiesmentioning

confidence: 99%

<p>Optimal management of thymic malignancies: current perspectives</p>

Drevet¹,

Collaud²,

Tronc³

et al. 2019

CMAR

View full text Add to dashboard Cite

Thymic epithelial tumors (TETs) belong to orphan oncology. The incidence of TETs is about 1.3-3.2 cases per million worldwide. Following pathology, evolution and prognosis are variable. The World Health Organization classification distinguishes thymomas and thymic carcinomas. TETs are composed of thymic epithelial tumoral cells and normal lymphocytes. The mean age at diagnosis is 50-60 years-old. There are no identified risk factors. TETs are frequently associated with paraneoplastic syndromes as myasthenia gravis. The complete R 0 surgical resection is the most significant prognosis factor on survival. In 2010, the French National Institute of Cancer labeled the RYTHMIC network as a specific tumor board including thoracic surgeons, oncologist, and radiation therapist to define standard of care for the management of TETs. The aim of the review was to update knowledge to optimize the standard of care.

show abstract

“…According to the morphology of epithelial cells as well as the lymphocyte-to-epithelial cell ratio, the World Health Organization (WHO) classification which was proposed in 2015 classified TETs into six subtypes (thymoma: types A, AB, B1, B2 and B3; thymic carcinoma: type C), which is recognized as the basis of the clinical treatment decision making and an independent prognostic factor in TETs [2][3][4]. Previous studies have shown that the invasiveness of each subtype increased in turn, and patients in low-risk TET (LTET) (types A, AB, B1) usually had more chances to be completely resected, lower tumor recurrence rate and higher survival rate than ones in high-risk TET (HTET) (types B2, B3, C) [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a CT-TA nomogram for preoperatively differentiating thymic epithelial tumor histologic subtypes

Ren

Zhang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Thymic epithelial tumors (TETs) are the most common primary tumors in the anterior mediastinum with considerable histologic heterogeneity. This study aimed to develop and validate a nomogram based on computed tomography (CT) and texture analysis (TA) for preoperatively predicting pathological classification for TET patients.Methods: Totally 172 patients with pathologically confirmed TET after surgery were retrospectively analyzed and randomly divided into a training cohort (n=120) and a validation cohort (n=52). Preoperative clinical demographic, CT signs and texture features of each patient were analyzed and prediction models were developed using the least absolute shrinkage and selection operator (LASSO) regression. The performance of models was evaluated and compared by the area under receiver operating characteristic (ROC) curve (AUC) and DeLong test. The clinical application value of models was determined through the decision curve analysis (DCA). Then a nomogram was developed based on the model with the best predictive accuracy and clinical utility and validated using the calibration plots.Results: Totally 87 patients with low-risk TET (LTET) (types A, AB, B1) and 85 patients with high-risk TET (HTET) (types B2, B3, C) were enrolled in this study. We separately constructed 4 prediction models for differentiating LTET from HTET using clinical, CT, texture features and their combination. These 4 prediction models achieved AUC values of 0.66, 0.79, 0.82, 0.88 in the training cohort and 0.64, 0.82, 0.86, 0.94 in the validation cohort, respectively. DeLong test and DCA analysis showed that the Combined model consisting of 2 CT signs and 2 texture parameters held the highest predictive efficiency and clinical utility ( p <0.05). A prediction nomogram was subsequently developed using the combined model’s 4 independently risk factors. The calibration curves indicated a good consistency between the actual observation and nomogram prediction for differentiating TET classifications.Conclusion: A prediction nomogram incorporating both the CT and texture parameters was constructed and validated in our study, which was conveniently used to facilitate the preoperative individualized prediction of simplified histologic subtypes in TET patients, assisting in clinical treatment decision making and achieving precision treatment.

show abstract

Thymic epithelial tumors express vascular endothelial growth factors and their receptors as potential targets of antiangiogenic therapy: A tissue micro array-based multicenter study

Cited by 34 publications

References 41 publications

Pembrolizumab in a Patient With Heavily Pre-Treated Squamous Cell Thymic Carcinoma and Cardiac Impairment: A Case Report and Literature Review

Pembrolizumab in a Patient With Heavily Pre-Treated Squamous Cell Thymic Carcinoma and Cardiac Impairment: A Case Report and Literature Review

<p>Optimal management of thymic malignancies: current perspectives</p>

Development and validation of a CT-TA nomogram for preoperatively differentiating thymic epithelial tumor histologic subtypes

Contact Info

Product

Resources

About