Purpose To study the risk factors for radiation-induced lung toxicity (RILT) after stereotactic body radiotherapy (SBRT) of the thorax. Methods Published studies on lung toxicity in patients with early stage non-small cell lung cancer (NSCLC) or metastatic lung tumors treated with SBRT were pooled and analyzed. The primary endpoint was RILT including pneumonitis and fibrosis. Data of RILT and risk factors were extracted from each study, and rates of grade 2-5 (G2+) and grade 3-5 (G3+) RILT were computed. Patient, tumor and dosimetric factors were analyzed for their correlation with RILT. Results Eighty-eight studies (7752 patients), that reported RILT incidence, were eligible. The pooled rates of G2+ and G3+ RILT from all 88 studies were 9.1% (95% CI: 7.15-11.4) and 1.8% (95% CI: 1.3-2.5), respectively. The median of median tumor sizes was 2.3 (range 1.4-4.1) cm. Among the factors analyzed, older patient age (P= 0.044) and larger tumor size (the greatest diameter) were significantly correlated with higher rates of G2+ (P= 0.049) and G3+ RILT (P= 0.001). Patients with stage IA vs. stage IB NSCLC had significantly lower risks of G2+ RILT (8.3% vs 17.1%, OR= 0.43, 95% CI: 0.29-0.64, P<0.0001). Among studies that provided detailed dosimetric data, the pooled analysis demonstrated a significantly higher mean lung dose (MLD) (P= 0.027) and V20 (P= 0.019) in patients with G2+ RILT comparing to that of grade 0-1 RILT. Conclusions The overall rate of RILT is relatively low after thoracic SBRT. Older age and larger tumor size are significant adverse risk factors for RILT. Lung dosimetry, specifically lung V20 and MLD also significantly affect RILT risk. Summary Risk factors for radiation-induced lung toxicity (RILT) after stereotactic body radiotherapy (SBRT) were analyzed from 88 published studies (7752 patients). The overall rate of RILT is relatively low after thoracic SBRT. Adverse risk factors for RILT after SBRT include older age, larger tumor size and greater lung dose-volume exposure as measured by mean lung dose and volume of lung receiving greater than 20 Gy.

BackgroundThere is no consensus regarding whether androgen deprivation therapy (ADT) is associated with cardiovascular disease (CVD) and cardiovascular mortality (CVM). The objective of this study was to determine the role of ADT for prostate cancer (PCa) in development of cardiovascular events (CVD and CVM).Methods and FindingsWe performed a meta-analysis from population-based observational studies comparing ADT vs control aimed at treating PCa in patients with PCa, reporting either CVD or CVM as outcome. Publications were searched using Medline, Embase, Cochrane Library Central Register of observational studies database up to May 31th 2014, and supplementary searches in publications from potentially relevant journals. 6 studies were identified with a total of 129,802 ADT users and 165,605 controls investigating the relationship between ADT and CVD. The incidence of CVD was 10% higher in ADT groups, although no significant association was observed (HR = 1.10, 95%CIs: 1.00–1.21; P = 0.06). For different types of ADT, CVD was related with gonadotropin-releasing hormone (GnRH) (HR = 1.19, 95%CIs: 1.04–1.36; P<0.001) and GnRH plus oral antiandrogen (AA) (HR = 1.46, 95%CIs: 1.03–2.08; P = 0.04), but not with AA alone or orchiectomy. For CVM, 119,625 ADT users and 150,974 controls from 6 eligible studies were included, pooled results suggested that ADT was associated with CVM (HR = 1.17, 95%CIs: 1.04–1.32; P = 0.01). Significantly increased CVM was also detected in GnRH and GnRH plus AA groups. When patients received other treatments (e.g. prostatectomy and radiotherapy) were ruled out of consideration, more increased CVD (HR = 1.19, 95%CIs: 1.08–1.30; P<0.001) and CVM (HR = 1.30, 95%CIs: 1.13–1.50; P<0.001) were found in men treated with ADT monotherapy.ConclusionsADT is associated with both CVD and CVM. Particularly, GnRH alone and GnRH plus AA can significantly increase the incidence of cardiovascular events in patients with PCa.

We previously observed that the HERV type K (HERV-K) envelope (env) protein was expressed in the majority of human breast tumors from a U.S. cohort of women from Texas. We also made the preliminary observation that the expression of HERV-K env transcripts was associated with markers of disease progression. In this follow-up study, env protein expression was evaluated immunohistochemically in an additional 195 paraffin-embedded breast tumors from a second U.S. patient cohort (Baltimore, Maryland) and in 110 tumors from Chinese patients. Moreover, we compared env transcript expression between fresh-frozen normal and cancerous breast tissues. We observed that while env mRNA and protein expression was undetectable in normal breast tissue and in a subset of uninvolved normal-appearing tissue adjacent to the tumor epithelium, it was overexpressed in most tumors. Furthermore, env expression was associated with breast cancer progression. In Baltimore cohort women, HERV-K tumor positivity was significantly associated with disease stage and lymph node metastasis. In Chinese women, HERV-K env positivity was significantly associated with tumor size, TNM stage, and lymph node metastases, which is consistent with the observations in the U.S. cohort. We also found that Chinese breast cancer patients with a high expression of HERV-K had a decreased overall survival compared with patients who had either a moderate or low HERV-K expression in their tumors (P = 0.049, χ(2) log rank test). In conclusion, the HERV-K env gene is expressed in the majority of breast cancers from U.S. or Chinese women but not in normal breast tissue. High expression of HERV-K env protein in breast cancer patients is associated with markers of disease progression and poor disease outcome, indicating that HERV-K env protein is a novel candidate prognostic marker for breast cancer.

Impact statementUltrasound-guided MWA is an effective and safe technique for the treatment of benign thyroid nodules. It can significantly reduce the nodule volume, improve the patients' clinical symptoms, has less complication, guarantees quick recovery, meets patients' aesthetic needs, and shows less interference on the physiological and psychological aspects of the body. MWA should be a good complement to traditional open surgery and has potentials in clinical applications. AbstractThe objective of the present study was to investigate the effectiveness and safety of ultrasound-guided microwave ablation in the treatment of benign thyroid nodules. A total of 474 benign thyroid nodules in 435 patients who underwent ultrasound-guided microwave ablation from September 2012 to August 2015 were included. Nodule volume and thyroid function were measured before treatment and at 1, 3, 6, and 12 months and subsequently after every 6 months. The nodule volume reduction rate and changes of thyroid function were evaluated. The volume of all thyroid nodules significantly decreased after ultrasound-guided microwave ablation. The average volume was 13.07 AE 0.95 ml before treatment, and 1.14 AE 0.26 ml at 12-months follow-up. The mean volume reduction rate was 90% and the final volume reduction rate was 94%. The volume reduction rate of mainly cystic nodules was significantly higher than that of simple solid and mainly solid nodules (all P < 0.05). The pretreatment volume of nodules was positively correlated with the final volume reduction rate at final followup (P ¼ 0.004). No serious complications were observed after treatment. In conclusion, ultrasound-guided microwave ablation is an effective and safe technique for treatment of benign thyroid nodules, and has the potential for clinical applications.

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Background The aim of this study was to evaluate the characteristics, diagnosis, prognosis, and effective treatment modalities of pregnancy‐associated breast cancer (PABC). Methods From 1 January 2005 to 31 December 2015, 142 patients with PABC were identified in the Cancer Institute and Hospital of Tianjin Medical University database. The clinicopathological features, treatment methods, and outcomes were retrospectively evaluated. Results The median age at diagnosis was 30 years. All patients presented with a palpable mass in the breast. The sensitivity of ultrasound and mammography in PABC diagnosis was 86% and 83.3%, respectively, which increased to 91.3% when a combination of mammography and ultrasound was used. The median tumor size was 5.5 cm, and 63.1% of patients had associated axillary lymph node metastases. The proportions of ER negative, PR negative and HER2 positive were 45.7%, 45.7% and 30%, respectively. The five‐year overall survival (OS) and disease‐free survival (DFS) rates were 76.8% and 63.5%, respectively. According to univariate analysis, T stage, N stage, and HER2 status were significant prognostic factors for OS and DFS. The time interval between the onset of the first symptom and the first meeting with a health professional was also significant for OS. Multivariate analysis showed that T stage and HER2 status were independent prognostic risk factors for OS and DFS. Conclusion PABC is an aggressive form of breast cancer associated with advanced stage at diagnosis. Despite the existing difficulties in diagnosis, imaging examinations are indispensable. Early diagnosis and multidisciplinary therapy, including anti‐HER2 targeted therapy, may be important to improve prognosis.

Purpose: Non-small cell lung cancer (NSCLC) metastasizes fairly often to the brain, but identifying which patients will develop brain metastases is problematic. The phosphoinositide 3-kinase (PI3K)-AKTmTOR signaling pathway is important in the control of cell growth, tumorigenesis, and cell invasion. We hypothesized that genotype variants in this pathway could predict brain metastasis in patients with NSCLC.Methods: We genotyped 16 single-nucleotide polymorphisms (SNP) in five core genes (PIK3CA, PTEN, AKT1, AKT2, and FRAP1) by using DNA from blood samples of 317 patients with NSCLC, and evaluated potential associations with the subsequent development of brain metastasis, the cumulative incidence of which was estimated with Kaplan-Meier analysis. Multivariate Cox regression analysis was used to analyze correlations between genotype variants and the occurrence of brain metastasis.Results: In analysis of individual SNPs, the GT/GG genotype of AKT1: rs2498804, CT/TT genotype of AKT1: rs2494732, and AG/AA genotype of PIK3CA: rs2699887 were associated with higher risk of brain metastasis at 24-month follow-up [respective HRs, 1.860, 95% confidence interval (CI) 1.199-2.885, P ¼ 0.006; HR 1.902, 95% CI 1.259-2.875, P ¼ 0.002; and HR 1.933, 95% CI 1.168-3.200, P ¼ 0.010]. We further found that these SNPs had a cumulative effect on brain metastasis risk, with that risk being highest for patients carrying both of these unfavorable genotypes (P ¼ 0.003).Conclusions: Confirmation of our findings, the first to indicate that genetic variations in PI3K-AKTmTOR can predict brain metastasis, in prospective studies would facilitate stratification of patients for brain metastasis prevention trials.

Translocation of the pro-apoptotic protein Bax from the cytosol to the mitochondria is a crucial step in DNA damage-mediated apoptosis, and is also found to be involved in mitochondrial fragmentation. Irradiation-induced cytochrome c release and apoptosis was associated with Bax activation, but not mitochondrial fragmentation. Both Bax and Drp1 translocated from the cytosol to the mitochondria in response to irradiation. However, Drp1 mitochondrial translocation and oligomerization did not require Bax, and failed to induce apoptosis in Bax deficient diffuse large B-cell lymphoma (DLBCL) cells. Using fluorescent microscopy and the intensity correlation analysis, we demonstrated that Bax and Drp1 were colocalized and the levels of colocalization were increased by UV irradiation. Using co-immuno-precipitation, we confirmed that Bax and Drp1 were binding partners. Irradiation induced a time-associated increase in the interaction between active Bax and Drp1. Knocking down Drp1 using siRNA blocked UV irradiation-mediated Bax mitochondrial translocation. In conclusion, our findings demonstrate for the first time, that Drp1 is required for Bax mitochondrial translocation, but Drp1-induced mitochondrial fragmentation alone is not sufficient to induce apoptosis in DLBCL cells.