Survival benefit of adjuvant chemoradiotherapy for positive or close resection margin after curative resection of pancreatic adenocarcinoma

BackgroundThis study was conducted to identify patients who may benefit from adjuvant chemoradiotherapy (CRT) for positive or close resection margin (RM) after curative resection of pancreatic adenocarcinoma.MethodsFrom 2004 to 2015, total of 472 patients with pancreatic adenocarcinoma underwent curative resection. After excluding patients with RM > 2 mm or unknown, remaining 217 patients were retrospectively analyzed. Forty-six (21.2%) patients were treated with adjuvant chemotherapy alone (CTx; mainly gemcitabine-based), 142 (65.4%) with adjuvant CRT (mainly upfront), and 29 (13.4%) patients didn’t receive any adjuvant therapy (noTx group).ResultsLocoregional recurrence rate was significantly lower in the CRT group (43.7%) than in the CTx group (71.7%) or noTx group (65.5%) (p = 0.001). Significant survival benefits of CRT over CTx (HR 0.602, p = 0.020 for overall survival (OS); HR 0.599, p = 0.016 for time to any recurrence (TTR)) were demonstrated in multivariate analysis. CRT group had more 5-year survivors than other groups. In the subgroup analysis, such benefits of adjuvant CRT over CTx was observed only in patients with head tumor & vascular RM > 0.5 mm, but not in patients with body/tail tumor or vascular RM ≤ 0.5 mm. In the CRT group, radiation dose≥54 Gy was significantly associated with better TTR and OS.ConclusionsAdjuvant CRT could improve TTR and OS compared to adjuvant CTx alone in patients with close RM under 2 mm. Radiation dose escalation may be beneficial when feasible. Modern CRT regimen–based randomized evidence is needed for these high-risk patients.     

ICRU89号报告的解读——放射物理篇

本篇综述对ICRU89号报告的放射物理相关内容进行了详细解读,希望为从事宫颈癌近距离放射治疗的同仁在放射物理相关方面提供借鉴。     

经典名方地黄饮子的古代文献考究

经典名方地黄饮子现代临床应用广泛,治疗多科疾病,尤其是内科病中的神经系统疾病较多,临床疗效确切,但目前尚未转化成中成药制剂。故笔者采用文献计量学的方法,搜集记载地黄饮子的中医古籍文献,筛选、整理出有效数据254条,涉及中医古籍144部,系统梳理和分析研究了地黄饮子的历史发展源流、主治病证、制方原理、用药剂量、制剂方法、煎服方法等,以期为经典名方的研发和临床应用提供古代文献证据支持。研究发现,地黄饮子出自金代医家刘河间所著《宣明论方》,由熟地黄、巴戟天、山茱萸、肉苁蓉、石斛、附子、五味子、官桂、白茯苓、麦门冬、藏菖蒲、远志12味药物组成,主治喑痱。后世记载的地黄饮子多遵从《宣明论方》中的方剂组成和主治,且临床应用有所扩展,在有主治病证记载的199条文献中,喑痱最多,约占总病证的一半;其次为中风,约占五分之二;亦用于暴喑、痿证、眩晕、遗尿等病证。地黄饮子治疗病证范围较广,但病机总属"肾中水火俱亏"。其制方独特,上下并治,标本兼顾,尤以治下治本为主。在有药物用量记载的56条文献中,约有三分之一继承了《宣明论方》的记载:"等分,上为末,每服3钱。"药物用量总体偏轻。制剂多为汤剂、煮散,在煎服方法上主张"浊药轻投""数滚即服""不计时候"。     

Predictors of Whole Breast Radiation Therapy Completion in Early Stage Breast Cancer Following Lumpectomy

BackgroundWhole breast radiation therapy (RT) has become standard of care in early stage breast cancer treatment following lumpectomy. Predictors of RT completion have been sparsely studied, with no previous nationwide examination of the impact of fractionation regimen on completion rate.Patients and MethodsThe National Cancer Database identified patients with early stage breast cancer having undergone lumpectomy and RT from 2004 through 2015. Fraction size of 1.8-2.0 Gray (Gy) was defined as standard fractionation (SFRT); 2.66-2.70 Gy/fraction as hypofractionation (HFRT). RT completion was defined as receipt of at least 46 Gy for SFRT and 40 Gy for HFRT. A multivariable logistic regression model characterized RT completion predictors.ResultsA total of 100,734 patients were identified where fraction size could be reliably characterized as above; more than 87% completed RT. Of these, 66.8% received SFRT, yet HFRT use significantly increased over time (5.2% increase/year; P < .0001). RT completion rates were significantly greater following HFRT (99.3%) versus SFRT (79.7%); patients receiving SFRT had higher odds of not completing RT (odds ratio, 41.5; 95% confidence interval, 36.6-47.1; P < .0001). Multivariable analysis revealed that African-American and Caucasian patients treated with SFRT versus HFRT had 22 and 43 times the odds of not completing RT, respectively (P < .0001).ConclusionsSFRT remained the majority of RT fractionation in the studied time period, although HFRT use has increased over time. Patients residing > 10 miles from a treatment facility or of African-American race had lower odds of completing RT, as were patients treated with SFRT versus HFRT. These findings suggest compliance advantages of HFRT for patients with early stage breast cancer having undergone lumpectomy.     

Abscopal effect in radioimmunotherapy

Abscopal effect is an interesting phenomenon in radiobiology that causes activation of immune system against cancer cells. Traditionally, this phenomenon was known as a suppressor of non-irradiated tumors or metastasis. However, it can be used as a stimulator of the immune system against primary tumor during radiotherapy. Immunotherapy, a novel tumor therapy modality, also triggers immune system against cancer. To date, some immunotherapy types have been developed. However, immune checkpoint blockade is a more common modality and some drugs have been approved by the FDA. Studies have shown that radiotherapy or immunotherapy administered alone have low efficiency for tumor control. However, their combination has a more potent anti-tumor immunity. For this aim, it is important to induce abscopal effect in primary tumors, and also use appropriate drugs to target the mechanisms involved in the exhaustion of cytotoxic CD8+T lymphocytes (CTLs) and natural killer (NK) cells. Among the different radiotherapy techniques, stereotactic body radiation therapy (SBRT) with some few fractionations is the best choice for inducing abscopal effect. On the other hand, programmed cell death 1 (PD-1) is known as one of the best targets for triggering anti-tumor immunity. This combination is known as the best choice among various strategies for radioimmunotherapy. However, there is the need for other strategies to improve the duration of immune system’s activity within tumor microenvironment (TME). In this review, we explain the cellular and molecular mechanisms behind abscopal effect by radiotherapy and evaluate the molecular targets which induce potent anti-tumor immunity.     

Utilization of hypofractionated radiation therapy in older glioblastoma patients

Background

Though the optimal treatment regimen in older patients with glioblastoma multiforme (GBM) remains to be established, multiple randomized studies have supported the use of hypofractionated (1–3?weeks) versus traditional regimens (6?weeks). Here we examine hypofractionated regimen practice patterns among older patients with GBM.

2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione,isolated from the root of Averrhoa carambola L., protects against diabetic kidney disease by inhibiting TLR4/TGFβ signaling pathway

ObjectiveDiabetic kidney disease (DKD) is the leading cause of death and disability of diabetes mellitus. However, there is still a lack of specific drugs for the treatment of DKD. The chief aim of this research is to investigate the role and mechanism of 2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) for DKD.MethodsWild type and TLR4 knockout mice were induced to diabetes. After 4-week treatment with DMDD, blood sugar, renal function, blood lipid and pathological changes were assessed. Real-time PCR, western blotting, and immunohistochemistry were employed to detect the expressions of TLR4, TGFβ1 and Smad2/3 in the renal tissue.ResultsDMDD improved the serum lipid and decreased fasting blood glucose levels in diabetic mice. CysC and urinary albumin levels increased markedly in the diabetic group, and they were obviously decreased after 4 weeks of DMDD treatment. Compared with the WT diabetic mice, the urinary albumin and CysC in the TLR4^-/- mice were expressed at lower levels. HE and Masson’s staining revealed that DMDD clearly ameliorated pathological changes and renal fibrosis. When TLR4 gene was knock out, the pathological was improved. Mechanistically, TLR4, TGF-β1 and Smad2/3 were obvious up-regulation in the renal tissues of diabetic mice. The expressions of these proteins were significantly down-regulated after DMDD treatment (p < 0.05). In the TLR4^-/- mice, mRNA and protein levels of TGF-β1 and Smad2/3 were obviously lower than those in the WT mice. In addition, IHC revealed that a strong in situ expressions of TLR4, TGF-β1 and Smad2/3 were seen in the kidney tissues of diabetic mice, which were distinctly weakened in the DMDD-treated mice. In the TLR4^-/- mice, however, expressions of TGF-β1 and Smad2/3 were not remarkable increase in the diabetic mice compared with normal mice.ConclusionsThese results strongly indicate that TLR4 is essential for DMDD protection against renal dysfunction in diabetic mice. Its hypoglycemic and anti-fibrosis effects were likely mediated by the TLR4/TGFβ signaling pathway.     

CBCT影像组学联合构建Nomogram模型预测食管癌放疗患者放射性肺炎

目的 通过对放疗疗程中不同时段CBCT图像的影像组学分析,寻找早期定量预测食管癌放疗放射性肺炎(RP)的参数,结合临床特征和肺剂量体积参数建立联合Nomogram模型并探讨这一模型对食管癌RP的预测价值。方法 回顾分析2017—2019年间临床资料、剂量学参数、CBCT图像资料完整的 96例胸中段食管鳞癌调强放疗患者资料,每例患者均分别获取放疗期间3个不同时段的肺CBCT图像。全组病例随机分成训练集(67例)和验证集(29例),以CBCT上双肺实质作为感兴趣区,运用3D-Slicer软件进行图像分割和特征提取,经LASSO-Logistics回归分析方法进行特征参数筛选并构建影像组学标签(Rad-score)。从3个不同时段建立的RP预测模型中选择最优模型联合经回归分析获得的最佳临床及剂量学参数,建立联合Nomogram模型,并进行受试者工作特征曲线分析,基于曲线下的面积(AUC)验证其诊断效能。结果 第一时段的影像组学预测模型优于其他两个时段,在训练集中的AUC值为0.700(95%CI为 0.568~0.832),敏感性和特异性分别为61.5%、75.0%;在验证集中的AUC值为0.765(95%CI为 0.588~0.941),敏感性和特异性分别为84.6%、64.7%。影像组学联合临床及剂量学构建的Nomogram模型在训练集中的AUC值为0.836(95%CI为 0.700~0.918),敏感性和特异性分别为96.0%、54.8%;在验证集中的AUC值为0.905(95%CI为 0.799~1.000),敏感性和特异性分别为92.9%、73.3%。联合Nomogram模型诊断效能最佳。结论 基于放疗早期肺CBCT影像组学特征构建的模型,对于食管癌RP具有一定的预测效能,Rad-score联合 肺V5Gy、肺 Dmean、肿瘤分期建立的Nomogram模型具有更好的预测准确性,可作为一种定量预测模型用于RP的预测。     

Writing your first paper: An informal guide for medical radiation sciences professionals*

Writing and submitting a paper can be a daunting prospect, especially the first time. One of the more challenging aspects is knowing how to begin. Countless projects in the workplace never make it past local dissemination or conference presentation. This informal guide will help you take that next step and begin the peer-reviewed publication journey.