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Abstract Background Genomic profiles of specific gene sets have been established to guide personalized treatment and prognosis for patients with breast cancer (BC). However, epigenomic information has not yet been applied in a clinical setting. ST14 encodes matriptase, a proteinase that is widely expressed in BC with reported prognostic value. Methods In this present study, we evaluated the effect of ST14 DNA methylation (DNAm) on overall survival (OS) of patients with BC as a representative example to promote the use of the epigenome in clinical decisions. We analyzed publicly available genomic and epigenomic data from 1361 BC patients. Methylation was characterized by the β-value from CpG probes based on sequencing with the Illumina Human 450 K platform. Results A high mean DNAm (β > 0.6779) across 34 CpG probes for ST14, as the gene-associated methylation (GAM) pattern, was associated with a longer OS after adjusting age, stage, histology and molecular features in Cox model (p value

Abstract In the era of immunotherapy, there lacks of a reliable genomic predictor to identify optimal patient populations in combined radiotherapy and immunotherapy (CRI). The purpose of this study is to investigate whether genomic scores defining radiosensitivity are associated with immune response. Genomic data from Merged Microarray-Acquired dataset (MMD) were established and the Cancer Genome Atlas (TCGA) were obtained. Based on rank-based regression model including 10 genes, radiosensitivity index (RSI) was calculated. A total of 12832 primary tumours across 11 major cancer types were analysed for the association with DNA repair, cellular stemness, macrophage polarisation, and immune subtypes. Additional 585 metastatic tissues were extracted from MET500. RSI was stratified into RSI-Low and RSI-High by a cutpoint of 0.46. Proteomic differential analysis was used to identify significant proteins according to RSI categories. Gene Set Variance Analysis (GSVA) was applied to measure the genomic pathway activity (18 genes for T-cell inflamed activity). Kaplan-Meier analysis was performed for survival analysis. RSI was significantly associated with homologous DNA repair, cancer stemness and immune-related molecular features. Lower RSI was associated with higher fraction of M1 macrophage. Differential proteomic analysis identified significantly higher TAP2 expression in RSI-Low colorectal tumours. In the TCGA cohort, dominant interferon-γ (IFN-γ) response was characterised by low RSI and predicted better response to programmed cell death 1 (PD-1) blockade. In conclusion, in addition to radiation response, our study identified RSI to be associated with various immune-related features and predicted response to PD-1 blockade, thus, highlighting its potential as a candidate biomarker for CRI.

Abstract Background This study aimed to compare the clinical outcomes of stereotactic ablative radiotherapy (SABR) and conventionally fractionated radiotherapy (CFRT) in hepatocellular carcinoma (HCC) patients with portal vein invasion (PVI). Methods HCC patients with PVI treated with radiotherapy from 2007 to 2016 were analysed. CFRT was administered at a median dose of 51.5 Gy (interquartile range, 45–54 Gy) with 1.8–3 Gy per fraction. SABR was administered at a median dose of 45 Gy (interquartile range, 40–48 Gy) with 6–12.5 Gy per fraction. Treatment efficacy, toxicity, and associated predictors were assessed. Results Among the 104 evaluable patients (45 in the SABR group and 59 in the CFRT group), the overall response rate (ORR, complete and partial response) was significantly higher in the SABR group than the CFRT group (62.2% vs. 33.8%, p = 0.003). The 1-year overall survival (OS) rate (34.9% vs. 15.3%, p = 0.012) and in-field progression-free survival (IFPS) rate (69.6% vs. 32.2%, p = 0.007) were also significantly higher in the SABR vs. CFRT group. All 3 rates remained higher in the SABR group after propensity score matching. Multivariable analysis identified SABR and a biologically effective dose ≥65 Gy as favourable predicators of OS. There was no difference between treatment groups in the incidence of radiation-induced liver disease or increase of Child-Pugh score ≥ 2 within 3 months of radiotherapy. Conclusions SABR was superior to CFRT in terms of ORR, OS, and IFPS. We suggest that SABR should be the preferred technique for HCC patients with PVI.

Background: This study determines the pain-reducing effect of CyberKnife radiosurgery in the treatment of spinal lesions. Materials and Methods: We evaluated the clinical outcomes of patients treated with CyberKnife radiosurgery for spinal lesions in 65 patients with 76 spinal lesions at Tri-Service General Hospital, Taipei, Taiwan, from July 2007 to May 2013. Pre- and post-treatment visual analog scale (VAS) scores for pain were obtained. Results: In the benign cases, 12 patients had a pretreatment VAS score of 7 (46.2%); 12 patients, 8 (46.2%); and 2 patients, 9 (7.7%). For the posttreatment VAS scores, 10 patients had a score of 1 (38.4%); 15 patients, 2 (57.7%); and 1 patient, 4 (3.8%). In the malignant cases, 2 patients had a pretreatment VAS score of 8 (28.6%); 3 patients, 9 (42.9%); and 2 patients, 10 (28.6%). For the posttreatment VAS scores, 1 patient had a score of 2 (14.3%) and 6 patients had a score of 3 (85.7%). In the metastatic cases, 15 patients had a pretreatment VAS score of 8 (46.9%); 7 patients, 9 (21.9%); and 10 patients, 10 (31.3%). For the posttreatment VAS scores, 3 patients had a score of 1 (9.4%); 11 patients, 2 (34.4%); 16 patients, 3 (50%); and 2 patients, 4 (6.3%). Wilcoxon signed-rank tests to compare the pre- and post-treatment VAS scores in each patient group showed significant decreases in all groups (P < 0.05 for all comparisons). Conclusions: Collectively, these results show that significant pain relief without obvious adverse effects can be achieved when treating spinal lesions using stereotactic radiosurgery.

Background: CyberKnife radiation therapy has a widely used system in the treatment of extracranial lesions. Implanting gold fiducial markers around a tumor is an important procedure for the planning and aiming of CyberKnife radiation therapy. Thus, the purpose of this study was to evaluate the feasibility, safety, and efficacy of percutaneous fiducial marker implantation of hepatic malignancies under sonographic guidance for CyberKnife radiation therapy. Materials and Methods: From April 2009 to November 2011, we retrospectively reviewed 30 percutaneous fiducial marker implantations in 30 patients with hepatic tumors. All patients underwent percutaneous fiducial marker implantation under sonographic guidance. The feasibility, safety, and efficacy of this technique were analyzed on immediate follow-up unenhanced computed tomography (CT) and 1-week follow-up contrast-enhanced CT. The efficacy of this technique was defined as implantation enabling adequate treatment planning and CT simulation. Results: All 30 patients (100%) had successful fiducial marker implantation under sonographic guidance. The mean number of fiducial markers implanted per patient was 4.30 (range: 4-6 seeds). There was one minor complication (3.33%, 1/30). All 30 patients successfully underwent CyberKnife radiation therapy after fiducial marker implantation. Conclusion: Sonographic-guided percutaneous fiducial marker implantation of hepatic malignancies is a feasible, safe, and effective technique for preparing patients before CyberKnife radiation therapy.

We investigated whether lower urinary tract infection (LUTI), including cystitis or urethritis, is associated with an increased risk of developing prostate cancer (PCa), in a nationwide population-based cohort study.We identified 14,273 men newly diagnosed with LUTI (9347 with cystitis, and 4926 with urethritis) between 1998 and 2011, from the Taiwan Longitudinal Health Insurance Database 2000. Each patient was randomly frequency-matched with 4 men without LUTI, based on age and index year of diagnosis. Cox's proportional hazard regression analysis was performed to estimate the effect of LUTI on the PCa risk.The risk of developing PCa was significantly higher in the cystitis cohort (adjusted HR = 1.46, 95% CI = 1.20-1.78) and in the urethritis cohort (adjusted HR = 1.72, 95% CI = 1.26-2.34) than in the group without LUTI. Further analyses indicated that patients with more than 5 medical visits for LUTI per year had a significantly greater risk of developing PCa.We found that cystitis or urethritis may play an etiological role in the development of PCa in Taiwanese men, particularly in those with repeated medical visits for cystitis or urethritis. Further studies are warranted on the association between LUTI and PCa in other countries, particularly where the prevalence of PCa is high.

OBJECTIVE:To evaluate the survival outcomes and prognostic factors of patients with advanced hepatocellular carcinoma (HCC) who underwent stereotactic ablative radiotherapy (SABR). METHODS:This retrospective study evaluated patients with advanced HCC who underwent SABR between December 2007 and July 2015. All patients had Barcelona Clinic Liver Cancer stage C disease and Child-Turcotte-Pugh (CTP) class A-B function. In-field control (IFC), overall survival (OS), prognostic factors, and toxicity were evaluated. RESULTS:In this study of 89 patients, the 3-year IFC rate was 78.1%, and the 1-year and 3-year OS rates were 45.9% and 24.3%, respectively. The multivariate analysis revealed that CTP class, the presence of main portal vein tumor thrombosis, and the presence of extrahepatic spread were independent predictors of OS. The expected median OS values among patients with ≥2, 1, and 0 predictors were 4.2, 8.6, and 26.4 months, respectively (p

Background: To analyze the local control of malignant lung tumors and survival of nonsmall cell lung cancer (NSCLC) patients after stereotactic ablative radiotherapy with CyberKnife. Materials and Methods: Patients with malignant lung tumors treated by CyberKnife between July 2007 and October 2010 at our institute were retrospectively reviewed. A total of 55 patients with 110 malignant lung tumors were included. There were 32 men and 23 women, and the median age was 67 years. There were 11 early-stage NSCLCs, while the other 44 patients with 99 lesions were metastatic lung tumors. The median gross tumor volume was 13.3 ml. Radiotherapy schedules include 40-60 Gy in 4-5 fractions, 45-60 Gy in 3 fractions and 30 Gy in 1 fraction. Results: The median follow-up time for patients alive was 34 months. The local control rates for all tumors were 96% at 1-year and 80% at 2 years. Univariate analysis demonstrated that target volume was important for local control. Biologically equivalent dose (BED) ≥100 Gy provided significantly higher chance to achieve a complete response than BED

Background: Brain edema induced by radiotherapy is a common complication in patients with brain tumors, for which medical treatment is the treatment of choice. Adjusted-Da-Chai-Ling-Tang, a Chinese herbal formulation, has been confirmed to be protective against the radiation-induced edema. In this study, we investigated the efficiency of adjusted-Da-Chai-Ling-Tang in radiation-induced brain edema in patients with brain tumors. Materials and Methods: A total of 46 patients with brain tumors treated with radiotherapy alone or combined with surgery were enrolled. These patients were divided into two groups: The experimental group with adjusted-Da-Chai-Ling-Tang and the control group with conventional medical treatment. Clinical data including symptoms and serologic results were collected pretreatment and on the 4 th , 7 th and 10 th day posttreatment. Magnetic resonance imaging of the brain was performed to investigate changes in brain edema. Results: Clinical symptoms including headache, dizziness, nausea/vomiting and fatigue significantly improved in the experimental group (P < 0.05). No difference in serological results was observed. Brain edema was significantly reduced in the experimental group in magnetic resonance imaging (P < 0.05). Conclusion: Adjusted-Da-Chai-Ling-Tang is effective in the treatment of radiation-induced brain edema in patients with brain tumors. No obvious side effects were observed.

The treatment of renal cell carcinoma (RCC) in patients diagnosed with chronic kidney disease (CKD) requires particular care in order to preserve the remaining renal function. The present study aimed to investigate the potential of a novel nephron-sparing treatment, which is capable of targeting tumors embedded deep within tissues. The present study analyzed three patients, with pre-existing CKD and multiple comorbidities, who were successfully treated for stage I RCC using the CyberKnife® stereotactic ablative radiotherapy (SABR) system. The total prescribed dose was 40 Gy in five fractions administered over five consecutive days. Treatment efficiency was determined using computed tomography scans of the tumors and periodic measurements of the glomerular filtration rate over a period of 12-40 months. Local control, defined as a radiologically stable condition, was achieved in all patients. Lung metastasis was observed in one patient nine months after SABR; however, the side-effects were generally mild and self-limiting. One patient developed renal failure 26 months after SABR, while the severity of CKD was only marginally altered in the other two patients and renal failure did not occur. In conclusion, in the present study, SABR with CyberKnife® was observed to be well tolerated in the patients, with an acceptable acute toxicity effect. Therefore, it may represent a potential therapeutic option for patients with early-stage RCC who have previously been diagnosed with CKD, but for whom other nephron-sparing treatments are contraindicated. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the efficacy of CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (SRS) for patients with pituitary adenoma. METHODS: We conducted a retrospective review of all patients treated by image-guided radiosurgery at our institution between August 2007 and June 2009. Twenty-two patients with pituitary adenoma were identified. The median follow-up period from date of treatment was 30.8 + 7.7months. The median patient age was 56 years. The mean tumor volume was 4.1 + 2.8 mL (range, 0.8-16.0 mL), and the prescribed dose was 25 Gy (5 Gy x 5). RESULTS: Tumors were treated with a mean coverage of 95.1 ± 1.3%(range 90.2-99.1%), a mean conformality index of 1.4 ± 0.4 (range, 1.2-1.8), and a mean treatment isodose line of 76.4 ± 3.0%(range70-83%). The primary endpoints were radiographic and endocrinological tumor control. The local radiographic control rate in this series was 100% (22/22). Radiographic evidence of tumor necrosis developed in 3 patients (13.7%). CONCLUSION: CyberKnife multisession radiosurgery of 25 Gy (5 Gy x 5) provided excellent local control with acceptable adverse effect in patients with pituitary adenoma post-transsphenoidal resection. This preliminary study provides data that supports the belief that the optic nerve and chiasm tolerate the above dosing regimens in perichiasmatic pituitary adenomas, and this dosing regimen may achieve satisfactory radiographic and endocrinological tumor control for post-transsphenoidal resection. [ABSTRACT FROM AUTHOR]

Background: To analyze the rate of larynx preservation in patients of locally advanced hypopharyngeal cancer treated with intensity modulated radiotherapy (IMRT) plus concurrent chemotherapy, and compare the results with patients treated with primary surgery. Methods: Between January 2003 and November 2007, 14 patients were treated with primary surgery and 33 patients were treated with concurrent chemoradiotherapy (CCRT) using IMRT technique. Survival rate, larynx preservation rate were calculated with the Kaplan-Meier method. Multivariate analysis was conducted for significant prognostic factors with Cox-regression method. Results: The median follow-up was 19.4 months for all patients, and 25.8 months for those alive. The 5-year overall survival rate was 33% and 44% for primary surgery and definitive CCRT, respectively (p = 0.788). The 5-year functional larynx-preservation survival after IMRT was 40%. Acute toxicities were common, but usually tolerable. The rates of treatment-related mucositis (≥ grade 2) and pharyngitis (≥ grade 3) were higher in the CCRT group. For multivariate analysis, treatment response and cricoid cartilage invasion strongly correlated with survival. Conclusions: IMRT plus concurrent chemotherapy may preserve the larynx without compromising survival. Further studies on new effective therapeutic agents are essential. [ABSTRACT FROM AUTHOR]