A comprehensive method for calculating total body irradiation

PurposeTo provide means for calculating the dose received by various tissues of the patient, calculate lung shield, and verify received dose using a phantom as a tool for quality assurance for a planned Total Body Irradiation (TBI) procedure in radiotherapy.MethodUsing Microsoft Visual Basic, MATLAB, and Python, a program for Total Body Irradiation Calculation in Radiotherapy (TBICR) is constructed. It uses patient translation and beam zone method for total body irradiation calculations to compute the proper dose received by the patient and determine the lung shield thickness. There are three main user-friendly interfaces in the application. The first one allows the user to upload the TBI topography and estimate the distances needed for TBI calculations. The second one enables the user to count the number of beam zones needed for each point and estimate the effective area (A_eff) for each level. The third interface estimates the velocity required to deliver the relative dose depending on patient separation, Monitor Units (MU), couch speed and travel distance. It allows the user to compute the required lung shield thickness, read any patient's CT DICOM file and acquire dose in any distinct location using machine learning model to predict the dose.ResultsThe TBICR software has been successfully validated by reproducing all of the manual calculations in an exact and timely manner. TBICR generated more accurate results and confirmed the absorbed dose to patient through measurements on Anderson phantom.ConclusionsA computer program for the calculation of total body irradiation (TBI) is described in full. The dose received at each point on the patient, the calculation of lung shield and the determination of the velocity and time required for the couch movement are all made possible using the software. The ease of use, precision, data storage and printing are some important features of the present software.     

肝细胞性肝癌骨转移的诊疗进展与预后因素研究

随着临床诊治水平的不断进步，肝细胞性肝癌（hepatocellular carcinoma，HCC）患者的总生存时间获得延长，但是HCC骨转移发生率则显著升高，HCC骨转移的筛查与诊治已成为全球性热点与难点问题。明确HCC骨转移的致病机制有助于临床肿瘤筛查及诊疗手段的提高，血管形成和上皮-间质转化（epithelial mesenchymal transition，EMT）是HCC骨转移的主要致病机制，骨微环境使得HCC骨转移持续发生。明确HCC骨转移的预后因素有利于对此类患者进行早期干预以延长患者总生存期，但目前尚未就HCC骨转移患者的治疗策略达成共识。本文就HCC骨转移分子病理学致病机制的研究进展进行综述，为早期筛查、精准诊断和个体化治疗提供依据。      

基于剂量组学预测肺癌患者放射性肺炎发生的研究

目的 探讨剂量组学在预测肺癌根治性放疗患者放射性肺炎发生中的应用潜能。方法 回顾性收集行根治性放疗的314例肺癌患者的临床资料、放疗剂量文件、定位及随访CT图像,根据临床资料及影像学随访资料对放射性肺炎进行分级,提取全肺的剂量组学特征,构建机器学习模型。应用1000次自助抽样法（bootstrap）的最小绝对值收敛和选择算子嵌套逻辑回归（LASSO‐LR）及1000次bootstrap的赤池信息量准则（AIC）向后法筛选与放射性肺炎相关的剂量组学特征,随机按照7∶3划分为训练集及验证集,应用逻辑回归建立预测模型,并应用ROC曲线及校正曲线评价模型的性能。结果 共提取120个剂量组学特征,经LASSO‐LR降维筛选得到12个特征进入“特征池”,再经过AIC向后法筛选,最终筛选出6个剂量组学特征进行模型构建,训练集AUC为0.77（95%CI为0.65~0.87）,独立验证集AUC为0.72（95%CI为0.64~0.81）。结论 利用剂量组学建立的预测模型具有预测放射性肺炎发生的潜力,但仍需继续纳入多中心数据及前瞻性数据进一步挖掘剂量组学的应用潜能。     

MicroRNA expression profiling of Chinese follicular lymphoma by microarray: A preliminary study

BackgroundMicroRNAs (miRNAs) have been widely regarded as crucial regulators in various biological processes involved in carcinogenesis. However, the comprehensive miRNA profiles of Chinese follicular lymphoma (FL) remains completely unknown.MethodsThe Exiqon miRCURY LNA™ microRNA Array (v.18.0) was used to detect the miRNA expression profiles of three Chinese FL samples, and compared to three reactive lymphatic nodes (RLN). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to confirm the selected miRNAs in different series. Three databases (miRAnda, miRBase and TargetScan) were used to predict the putative target genes. Bioinformatic analysis (gene ontology analysis and pathway analysis) was performed for further evaluation.ResultsThe microarray assay demonstrated that 1643 miRNAs were expressed; in which 103 miRNAs were upregulated and 68 miRNAs were downregulated, according to P-value (< 0.05) and fold change (FC > 2-fold). Furthermore, qRT-PCR was used to confirm that miR-17-5p, miR-20a-5p and miR-19a-3p were upregulated, and miR-3615 was downregulated (P < 0.05). Bioinformatic analysis (gene ontology analysis and pathway analysis) was used for further evaluation. Pathway analysis indicated that 25 pathways corresponded to differentially expressed miRNAs (P-value cut-off is 0.05). Furthermore, miR-17-5p, miR-20a-5p and miR-19a-3p were validated by qRT-PCR in an independent series including five FL3a and five RLN cases. Data analysis revealed that the changing trend of miR-19a-3p and miR-17-5p expression in the independent series was basically identical with that of the microarray data.ConclusionsOur results are the first to reveal the miRNA expression profiling of Chinese FL and three upregulated miRNAs. Furthermore, the expression of miR-19a-3p and miR-17-5p were found to be significantly upregulated in FL3a. Further study needs to be urgently performed to reveal its potential role in the pathogenesis of FL in the near future.     

Is the autophagy a friend or foe in the silver nanoparticles associated radiotherapy for glioma？

Malignant glioma is the most common intracranial tumor with a dismal prognosis. The radiosensitizing effect of silver nanoparticles (AgNPs) on glioma both in vitro and in vivo had been demonstrated in the previous studies of our group. However, the underlying mechanism is still unclear. Consistent with previous studies, a size and dose dependent antitumor effect and significant radiosensitivity enhancing effect of AgNPs were observed in our experiment system. We also found that cell protective autophagy could be induced by AgNPs and/or radiation, which was verified by the use of 3-MA. The mechanism through which had autophagy and the enhancement of radiosensitivity taken place was further investigated with inhibitors of ERK and JNK pathways. We demonstrated that ERK and JNK played pivotal roles in the radiosensitivity enhancement. Inhibiting ERK and JNK with U0126 and SP600125 respectively, we found that the autophagy level of the cells treated with AgNPs and radiation were attenuated. Moreover, SP600125 down-regulated the apoptosis rate of the co-treated cells significantly. Taken together, the present study would have important impact on biomedical applications of AgNPs and clinical treatment for glioma.     

Tongue cancer treatment and oncological outcomes: The role of glossectomy classification

BackgroundNowadays surgery remains the gold standard of treatment for tongue cancer. Via a more clear and precise terminology, the glossectomy classification by Ansarin et al. facilitates shared communication between surgeons, allowing comparison between published research and improving surgical practice and patient care. To establish the association of glossectomies, according to their classification by Ansarin et al. with overall survival (OS), disease-free survival (DSF), and cause-specific survival (CSS) in tongue cancer, we conducted a systemic retrospective study on 300 consecutive patients affected by primary oral tongue cancer and treated with surgery at the European Institute of Oncology, IRCCS (IEO).MethodsThree hundred patients with tongue squamous cell carcinoma and treated at the Division of Otorhinolaryngology and Head and Neck Surgery of the European Institute of Oncology, IRCCS were cataloged according to the glossectomy classification. OS, DFS, and CSS were compared by surgical treatments.ResultsOS-5yrs was 80% for the type I glossectomy group, 75% for type II, 65% for type III, and 35% for type IV-V. DFS-5yrs was 74%, 60%, 55%, and 27%, respectively for I, II, III, and IV-V glossectomy group; CSS-5yrs was 82%, 80%, 72%, and 48%, respectively for I, II, III, and IV-V glossectomy group (p < 0.01).ConclusionsThis study confirmed that the application of the glossectomy classification was statistically correlated with patients' oncological outcomes.     

Using arterial spin labeling blood flow and its histogram analysis to distinguish early-stage nasopharyngeal carcinoma from lymphoid hyperplasia

To investigate the feasibility of arterial spin labeling (ASL) blood flow (BF) and its histogram analysis to distinguish early-stage nasopharyngeal carcinoma (NPC) from nasopharyngeal lymphoid hyperplasia (NPLH).Sixty-three stage T1 NPC patients and benign NPLH patients underwent ASL on a 3.0-T magnetic resonance imaging system. BF histogram parameters were derived automatically, including the mean, median, maximum, minimum, kurtosis, skewness, and variance. Absolute values were obtained for skewness and kurtosis (absolute value of skewness [AVS] and absolute value of kurtosis [AVK], respectively). The Mann–Whitney U test, receiver operating characteristic curve, and multiple logistic regression models were used for statistical analysis.The mean, maximum, and variance of ASL BF values were significantly higher in early-stage NPC than in NPLH (all P < 0.0001), while the median and AVK values of early-stage NPC were also significantly higher than those of NPLH (all P < 0.001). No significant difference was found between the minimum and AVS values in early-stage NPC compared with NPLH (P = 0.125 and P = 0.084, respectively). The area under the curve (AUC) of the maximum was significantly higher than those of the mean and median (P < 0.05). The AUC of variance was significantly higher than those of the other parameters (all P < 0.05). Multivariate analysis showed that variance was the only independent predictor of outcome (P < 0.05).ASL BF and its histogram analysis could distinguish early-stage NPC from NPLH, and the variance value was a unique independent predictor.     

Care of Seniors with Breast Cancer – Treatment Received and Refining Decision Making

AimsTreatment decisions for older patients with breast cancer are complex and evidence is largely extrapolated from younger populations. Frailty and comorbidity need to be considered. We studied the baseline characteristics and treatment decisions in older patients in Christchurch with breast cancer and assessed survival outcomes and prognostic/discriminatory performance of several tools.Materials and methodsWe searched the Canterbury Breast Cancer Registry and identified patients aged 70 years or older at diagnosis with invasive, non-metastatic breast cancer between 1 June 2009 and 30 June 2015. We retrieved demographics, treatment and outcome information. Overall survival and breast cancer-specific survival were estimated. Tools analysing performance status and comorbidity were assessed for their prognostic and discriminatory power.ResultsIn total, 440 patients were identified. Primary surgery was carried out for 362 patients (82.3%): breast-conserving surgery in 114 (of whom 88.6% received radiation therapy); mastectomy in 248 (of whom 24.6% received radiation). Hormone therapy was given for 265 (71.1%) patients with oestrogen receptor-positive cancers. Two hundred and seventy-four (62.3%) patients received full standard treatment, which was associated with significantly improved 5-year survival and 5-year breast cancer-specific survival. The median estimated overall survival was 8.2 years (95% confidence interval 7.3–9.1 years). Of those who died, 71.3% of deaths were due to causes other than breast cancer or unknown causes. The comorbidity-adjusted life expectancy (CALE) showed partial prognostic accuracy. CALE, Charlson and Eastern Cooperative Oncology Group tools all showed discriminatory value.ConclusionIn this population-based series of older patients with breast cancer, showing high levels of primary and adjuvant treatment, patients were more likely to die of causes other than breast cancer. Performance status and comorbidity tools showed prognostic and discriminatory potential in this population supporting their use in treatment decision making. CALE showed the most potential to improve treatment decisions but requires validation in this population to improve prognostic accuracy.     

Cellular immunotherapy in breast cancer: The quest for consistent biomarkers

Breast cancer is the most common malignancy in women worldwide, with a relatively high proportion of patients experiencing resistance to standard treatments. Cellular immunotherapy (CI), which is based on the extraction, modification, and re-infusion of the patient’s immune cells, is showing promising results in these patients. Among CI possible approaches, adoptive cell therapy (ACT) and dendritic cell (DC) vaccination are the most comprehensively explored in both primary/translational research studies and clinical trials. ACT may include the use of tumor-infiltrating lymphocytes (TILs), T cell receptor (TCR)-, or chimeric antigen receptor (CAR)-engineered T-cells. There are indications suggesting that a biomarker-based approach might be beneficial in effectively selecting breast cancer patients for CI. Here, we sought to provide the current knowledge of CI in breast cancer, focusing on candidate biomarkers, ongoing clinical trials, limitations, and immediate future perspectives.