Thymoma and thymic carcinoma are thymic epithelial tumors (TETs). We performed a molecular profiling to investigate the pathogenesis of TETs and identify novel targets for therapy. We analyzed 37 thymomas (18 type A, 19 type B3) and 35 thymic carcinomas. The sequencing of 50 genes detected nonsynonymous mutations in 16 carcinomas affecting ALK, ATM, CDKN2A, ERBB4, FGFR3, KIT, NRAS and TP53. Only two B3 thymomas had a mutation in noncoding regions of the SMARCB1 and STK11 gene respectively. Three type A thymomas harbored a nonsynonymous HRAS mutation. Fluorescence in situ hybridization detected in 38 % of carcinomas a CDKN2A, in 32 % a TP53 and in 8 % an ATM gene deletion, whereas only one B3 thymoma exhibited a CDKNA deletion, and none of the type A thymomas showed a gene loss. Sequencing of the total miRNA pool of 5 type A thymomas and 5 thymic carcinomas identified the C19MC miRNA cluster as highly expressed in type A thymomas, but completely silenced in thymic carcinomas. Furthermore, the miRNA cluster C14MC was downregulated in thymic carcinomas. Among non-clustered miRNAs, the upregulation of miR-21, miR-9-3 and miR-375 and the downregulation of miR-34b, miR-34c, miR-130a and miR-195 in thymic carcinomas were most significant. The expression of ALK, HER2, HER3, MET, phospho-mTOR, p16INK4A, PDGFRA, PDGFRB, PD-L1, PTEN and ROS1 was investigated by immunohistochemistry. PDGFRA was increased in thymic carcinomas and PD-L1 in B3 thymomas and thymic carcinomas. In summary, our results reveal genetic differences between thymomas and thymic carcinomas and suggest potential novel targets for therapy.Electronic supplementary materialThe online version of this article (doi:10.1007/s12253-016-0144-8) contains supplementary material, which is available to authorized users.

Purpose The goal of our study was comparison of external beam radiotherapy (EBRT) and I‑125 seeds brachytherapy in terms of biochemical control and development of late gastrointestinal and genitourinary side effects. Patients and methods 477 low-risk prostate cancer patients treated between 2000 and 2019 at our department using either I‑125 seeds brachytherapy or EBRT with a dose of 74 or 78 Gy were reviewed for our analysis. 213 patients were treated with EBRT and 264 with seeds. Results Patients were followed up yearly with a median follow-up of 70 (3–192) months. The biochemical no evidence of disease (bNED) rates after 5 years were 95% for both EBRT and seeds, and after 10 years 87% for EBRT and 94% for seeds using the Phoenix criteria, although no significant difference was observed. Concerning gastrointestinal side effects, EBRT showed significantly higher rates of RTOG grade ≥2 toxicity compared to seeds, but at no point in follow-up more than 15% of all patients. On the other hand, genitourinary side effects were significantly more prevalent in patients treated with seeds, with 40% RTOG grade ≥2 toxicity 12 months after treatment. Nevertheless, both types of side effects decreased over time. Conclusion Both EBRT and seeds provide excellent biochemical control with bNED rates after 10 years of about 90%. In terms of side effects, patients treated with seeds show higher grades of genitourinary side effects, while patients treated with EBRT show higher grades of gastrointestinal side effects.

Fetal inflammatory response syndrome is associated with increased neonatal morbidity and mortality. The aim of the present study was to evaluate the dynamics of the plasmatic value of pro-inflammatory cytokines: tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and neutrophil activating peptide 78 (ENA-78) and the anti-inflammatory cytokine IL-10 in the first and third day of life and the correlation with neonatal morbidities and mortality. The current research was designed as a prospective case control study included 80 neonates hospitalized at the 3rd level Neonatal Intensive Care Unit (NICU),

Purpose This study’s objective was the comparison of external beam radiotherapy (EBRT) and I‑125 seed brachytherapy regarding clinical outcome and development of side effects. Patients and methods In all, 462 localized intermediate-risk prostate cancer patients treated between 2000 and 2019 at our department using either I‑125 seed brachytherapy or EBRT with a dose of 74 or 78 Gy were included: 297 patients were treated with EBRT and 165 with seeds. Biochemical no evidence of disease (bNED) rates according to Phoenix definition as well as late gastrointestinal and urogenital side effects (EORTC/RTOG) were assessed. Results Patients were followed up yearly with a median follow-up of 54 (3–192) months. Observed bNED rates for 74 Gy, 78 Gy and seeds were 87, 92, and 88% after 5 years and 71, 85, and 76% after 9 years, respectively. No significant differences were found comparing seeds with 74 Gy (p = 0.81) and 78 Gy (p = 0.19), as well as between 74 and 78 Gy (p = 0.32). Concerning gastrointestinal side effects, EBRT showed significantly higher rates of RTOG grade ≥ 2 toxicity compared to seeds, but at no point of the follow-up more than 10% of all patients. However, genitourinary side effects were significantly more prevalent in patients treated with seeds, with 33% RTOG grade ≥ 2 toxicity 12 months after treatment. Nevertheless, both types of side effects decreased over time. Conclusion Favorable intermediate-risk prostate cancer patients can be treated either by external beam radiotherapy (74/78 Gy) or permanent interstitial seed brachytherapy.

Background The aim of the study was to evaluate the development of treatment of primary high-risk prostate cancer in regards to biochemical no evidence of disease (bNED), acute and late gastrointestinal (GI) and genitourinary (GU) side effects. Patients and methods Primary high-risk prostate cancer patients treated between 1994 and 2016 were included. Applied doses ranged from 60 to 80 Gy, with a dose of 1.8 or 2 Gy per fraction. Techniques were either 3D conformal or intensity modulated radiotherapy and volumetric intensity modulated arc therapy. Results 142 patients were treated with doses up to 70 Gy (median dose 66 Gy; 66 Gy group), 282 with doses between 70 and 76 Gy (median dose 74 Gy; 74 Gy group), and 141 with doses >76 Gy (median dose 78 Gy; 78 Gy group). The median follow-up was 48 months. The bNED rates were 50% after 5 years and 44% after 9 years in the 66 Gy group; 65% and 54%, respectively, in the 74 Gy group; and 83% and 66%, respectively, in the 78 Gy group (p = 0.03 vs. 74 Gy and p < 0.0001 vs. 66 Gy). We found a higher rate of acute GI side effects in the 78 Gy group compared to the other groups, but not in maximum acute GU side effects and late maximum GI and GU effects. Conclusions High-risk prostate cancer patients treated with doses of 78 Gy had significantly better bNED rates. Compared to the historical 66 Gy group, 50% more patients achieved bNED after a follow-up of 9 years.

Purpose Hypofractionated radiotherapy for prostate cancer is well established for definitive treatment, but not well defined in the postoperative setting. The purpose of this analysis was to assess oncologic outcomes and toxicity in a large cohort of patients treated with conventionally fractionated three-dimensional (3D) conformal radiotherapy (CF) and hypofractionated volumetric modulated arc therapy (HF) after radical prostatectomy. Methods Between 1994 and 2019, a total of 855 patients with prostate carcinoma were treated by postoperative radiotherapy using CF (total dose 65–72 Gy, single fraction 1.8–2 Gy) in 572 patients and HF (total dose 62.5–63.75 Gy, single fraction 2.5–2.55 Gy) in 283 patients. The association of treatment modality with biochemical control, overall survival (OS), and gastrointestinal (GI) and genitourinary (GU) toxicity was assessed using logistic and Cox regression analysis. Results There was no difference between the two modalities regarding biochemical control rates (77% versus 81%, respectively, for HF and CF at 24 months and 58% and 64% at 60 months; p = 0.20). OS estimates after 5 years: 95% versus 93% (p = 0.72). Patients undergoing HF had less frequent grade 2 or higher acute GI or GU side effects (p = 0.03 and p = 0.005, respectively). There were no differences in late GI side effects between modalities (hazard ratio 0.99). Median follow-up was 23 months for HF and 72 months for CF (p < 0.001). Conclusion For radiation therapy of resected prostate cancer, our analysis of this largest single-centre cohort (n = 283) treated with hypofractionation with advanced treatment techniques compared with conventional fractionation did not yield different outcomes in terms of biochemical control and toxicities. Prospective investigating of HF is merited.

Purpose To describe a local radio-oncological treatment for patients with prostate cancer that metastasized to either the lymph nodes or distant regions. Methods and materials We included 133 patients with prostate cancer that displayed either distant metastases (DM) or lymph node metastases alone (NM) and were treated between 2004 and 2019. All patients underwent computed tomography and a bone scan or 18F- or prostate-specific membrane antigen-targeted positron emission tomography. Patients received local external beam radiation therapy to the prostate to achieve local control (60–81.4 Gy to the prostate, and 45–50.4 Gy to pelvic lymph nodes), with either the 3D conformal (4-field box) or volumetric modulated arc therapy technique. A urologist prescribed additional therapy. Results We included 51 patients with DM and 82 patients with NM. The mean follow-up was 42 months for all patients. The groups were similar in T stage, initial prostate-specific antigen, histology, androgen deprivation therapy, age, treatment techniques, and prescribed doses, but different in lymph node inclusion and follow-up times. In the NM and DM groups, the 5‑year biochemical recurrence-free rates were 52% and 24%, respectively (p < 0.0001); the 5‑year disease-specific survival rates were 92% and 61%, respectively (p = 0.001); and the 5‑year OS rates were 77% and 48%, respectively (p = 0.01). The groups had similar acute and late gastrointestinal and genitourinary side effects, except that late genitourinary side effects occurred significantly more frequently in the NM group (p = 0.01). Conclusions DM was associated with significantly worse outcomes than NM. The long-term survival of patients with metastatic prostate cancer was low.

Background Evidence regarding the effects of fiducials in image-guided radiotherapy (IGRT) for tumor control and acute and late toxicity is sparse. Patients and methods Patients with primary low- and intermediate-risk prostate cancer, 40 with and 21 without gold fiducial markers (GFM), and treated between 2010 and 2015 were retrospectively included. The decision for or against GFM implantation took anaesthetic evaluation and patient choice into account. IGRT was performed using electronic portal imaging devices. The prescribed dose was 78 Gy, with 2 Gy per fraction. Biochemical no evidence of disease (bNED) failure was defined using the Phoenix criteria. Acute and late gastrointestinal (GI) and genitourinary toxicity (GU) were assessed using the Radiation Therapy Oncology Group criteria. Results Most patients did not receive GFM due to contraindications for anaesthesia or personal choice (60% and 25%). Regarding tumor control, no significant differences were found regarding bNED and overall and disease-specific survival (p = 0.61, p = 0.56, and p > 0.9999, respectively). No significant differences in acute and late GI (p = 0.16 and 0.64) and GU toxicity (p = 0.58 and 0.80) were observed. Conclusions We were unable to detect significant benefits in bNED or in early or late GI and GU side effects after GFM implantation.