Total body irradiation: Significant dose sparing of lung tissue achievable by helical tomotherapy

PurposeTotal body irradiation (TBI) is an important procedure in the conditioning for bone marrow and hematopoietic stem cell transplantation. Doses up to 12 Gy are delivered in hyperfractionated regimes. TBI performed with helical Tomotherapy® (Accuray, Madison, Wisconsin, USA) is an alternative to conventional techniques to deliver dose in extended target volumes with the possibility of simultaneous dose sparing to organs at risk. In this study we focused on maximum dose reduction to the lungs in TBI using helical Tomotherapy®.Material and methodsForty treatment plans of patients who received TBI were calculated with TomoH® (Accuray, Madison, Wisconsin, USA, Version 2.0.4) with a dose of 12 Gy delivered in six equal fractions (2 × 2 Gy/day). Planning iterations necessary to accomplish ICRU 83 report should be less than 250. Treatment time should be practicable in daily routine (<60 min.). Besides the usual contouring of organs at risk special contouring was required for optimization processes which focused on maximum dose sparing in the central lung tissue. Dose constraints (D2, D98, D99) were predefined for target volumes (i.e. PTV TBI D99: 90% of prescribed dose). Homogeneity index <0.15 was defined for acceptability of the treatment plan.ResultsFor all patients acceptable treatment plan fulfilling the predefined constraints were achievable. An average time of 46 min is required for treatment. Thirty-four of forty patients fulfilled D2 in the PTV TBI. Four patients failed D2 due to a high BMI >28 (maximum dose 13.76 Gy = 114.7%). The D98 in the PTV TBI was not reached by 2/40 patients due to BMI > 31 (minimum dose 11.31 Gy = dose coverage of 94.2%). Also these two patients failed the homogeneity index <0.15. The mean lung dose over all patients of the right lung was 7.18 Gy (range 6.4–9.5 Gy). The left lung showed a median (D50) dose of 7.9 Gy (range 6.7–9.3 Gy). Central lung dose showed a mean dose (D50) of 5.16 Gy (range 4.02–7.29 Gy). The D80 of the central lung showed an average dose of 3.87 Gy.ConclusionsTotal body irradiation using helical Tomotherapy® can be delivered with maximum lung tissue sparing (<6 Gy) but without compromise in adjacent PTV TBI structures (i.e. ribs, heart). High conformity and homogeneity in extended radiation volumes can be reached with this technique in an acceptable planning and treatment time. Limitations may occurred in patients with high body mass index.     

Towards offline PET monitoring of proton therapy at MedAustron

The characteristic depth-dose profile of protons traveling through material is the main advantage of proton therapy over conventional radiotherapy with photons or electrons. However, uncertainties regarding the range of the protons in human tissue prevent to exploit the full potential of proton therapy. Therefore, a non-invasive in-vivo dose monitoring is desired. At the ion beam center MedAustron in Wiener Neustadt/Austria, patient treatment with proton beams started in December 2016. A PET/CT is available in close vicinity of the treatment rooms, exclusively dedicated to offline PET monitoring directly after the therapeutic irradiation. Preparations for a patient study include workflow tests under realistic clinical conditions using two different phantoms, irradiated with protons prior to the scan in the PET/CT. GATE simulations of the C-11 production are used as basis for the prediction of the PET measurement. We present results from the workflow tests in comparison with simulation results, and by this, we demonstrate the applicability of the PET monitoring at the MedAustron facility.     

Targeting the PI3K/AKT/mTOR pathway in biliary tract cancers: A review of current evidences and future perspectives

Biliary tract cancers (BTCs) are a group of invasive neoplasms, with increasing incidence and dismal prognosis. In advanced disease, the standard of care is represented by first-line chemotherapy with cisplatin and gemcitabine. In subsequent lines, no clear recommendations are currently available, highlighting the need for novel therapeutic approaches.The PI3K/AKT/mTOR pathway is a core regulator of cell metabolism, growth and survival, and is involved in BTCs carcinogenesis and progression. Mutations, gene copy number alterations and aberrant protein phosphorylation of PI3K, AKT, mTOR and PTEN have been thoroughly described in BTCs and correlate with poor survival outcomes.Several pre-clinical evidences state the efficacy of PI3K/AKT/mTOR pathway inhibitors in BTCs, both in vitro and in vivo. In the clinical setting, initial studies with rapamycin analogs have shown interesting activity with an acceptable toxicity profile. Novel strategies evaluating AKT and PI3K inhibitors have risen serious safety concerns, pointing out the need for improved patient selection and increased target specificity for the clinical development of these agents, both alone and in combination with chemotherapy.This review extensively describes the role of the PI3K/AKT/mTOR pathway in BTCs and examines the rationale of its targeting in these tumors, with particular focus on clinical activity, toxicities and perspectives on further development of PI3K/AKT/mTOR pathway inhibitors.     

Pharmacokinetics,safety and metabolite profiling of minesapride,a novel 5-HT4 receptor partial agonist,in healthy elderly and young subjects

Minesapride is a novel 5-hydroxytryptamine 4 (5-HT₄) receptor partial agonist that is expected to show efficacy in patients with irritable bowel syndrome with predominant constipation and functional constipation. An open-label study was conducted to evaluate pharmacokinetics (PK) and safety of minesapride. Japanese subjects, 12 elderly and 12 young, received a single oral dose of minesapride 40 mg/day in the fasted state. Metabolite profiles were also investigated in this clinical study and in an in vitro study using cryopreserved hepatocytes. Clinical results showed that minesapride was rapidly absorbed (C_max: 2302.1 ng/mL in the elderly group, 2117.5 ng/mL in the young group), and the plasma concentration then decreased with half-life of approximately 7 h. There were no notable PK differences between elderly and young groups. No serious adverse events (AEs) were observed. The only AE that occurred in 2 or more subjects was diarrhea. Metabolite profiles in plasma and urine were similar between elderly and young groups. No major metabolites exceeded 10% of unchanged minesapride, and results of the in vitro study suggested that there were no human-specific metabolites. From the viewpoints of PK and metabolite profiling, no dose adjustment of minesapride is warranted in elderly population without renal or hepatic impairment.     

不同剂量A型肉毒毒素肌注对脑卒中后肌痉挛患者肌力和步行功能的影响

目的探讨不同剂量A型肉毒毒素肌注对脑卒中后肌痉挛患者肌力和步行功能的影响。方法前瞻性选取延安大学咸阳医院2015年8月至2017年8月收治的96例卒中后恢复期患者,按随机数表法分为大剂量组、中剂量组与小剂量组,各32例。三组均在常规康复训练基础上联合A型肉毒毒素肌注治疗其中大剂量组注射剂量400 U,中剂量组300 U/,小剂量组200 U,浓度均为50 U/ml。比较三组A型肉毒毒素起效时间与持续时间,治疗前与治疗后3个月的肌力恢复情况(采用改良A shworth分级评分评价)、步行功能(采用Holden步行功能评估)、10 m步行时间与日常生活能力(应用改良Barthel指数评估)、临床神经功能缺损程度(采用NDS评分)及不良反应总发生率。结果大剂量组起效时间明显较中剂量组与小剂量组更快,持续时间较中剂量组与小剂量组更长(P<0.05)。三组治疗前的Ashworth评分、Holden评分、10 m步行时间与BI指数的差异无统计学意义(P>0.05);治疗后3个月三组Ashworth评分与10 m步行时间均较治疗前显著减小、Holden评分与BI指数较治疗前显著增大(P<0.05)。大剂量组治疗后3个月的Ashworth评分与10 m步行时间显著低于中剂量组与小剂量组、Holden评分与BI指数显著高于中剂量组与小剂量组(P<0.05)。治疗后3个月三组NDS评分均较治疗前显著减小(P<0.05)。大剂量组治疗后3个月的NDS评分显著低于中剂量组与小剂量组(P<0.05)。大剂量组与中剂量组不良反应总发生率9.38%与3.13%,差异无统计学意义(P>0.05)。结论A型肉毒毒素可促进卒中后肌痉挛患者肌力与步行功能的恢复,提高日常生活能力,且大剂量组应用的起效时间最快、持续时间最长,效果最优,同时不良反应未见明显增加,为最佳应用剂量。     

局部晚期非小细胞肺癌放疗剂量提升研究进展

局部晚期非小细胞肺癌的RTOG0617研究显示进一步提高放疗剂量并没有带来生存获益,这促进了剂量提升策略的改变。目前多项研究通¹⁸FDG高摄取区域局部加量、同步加量调强放疗、改变剂量分割模式等探索更为有效的剂量提升手段,并取得一系列进展。PET-CT技术及调强放疗技术的广泛应用,为放疗剂量优化和提升提供了广阔空间。     

Dose calculation of dynamic trajectory radiotherapy using Monte Carlo

Purpose

Using volumetric modulated arc therapy (VMAT) delivery technique gantry position, multi-leaf collimator (MLC) as well as dose rate change dynamically during the application. However, additional components can be dynamically altered throughout the dose delivery such as the collimator or the couch. Thus, the degrees of freedom increase allowing almost arbitrary dynamic trajectories for the beam. While the dose delivery of such dynamic trajectories for linear accelerators is technically possible, there is currently no dose calculation and validation tool available. Thus, the aim of this work is to develop a dose calculation and verification tool for dynamic trajectories using Monte Carlo (MC) methods.

A multimodal approach using TMS and EEG reveals neurophysiological changes in Parkinson's disease

IntroductionAlterations in large scale neural networks leading to neurophysiological changes have been described in Parkinson's disease (PD). The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) has been suggested as a promising tool to identify and quantify neurophysiological mechanisms. The aim of this study was to investigate specific changes in electrical brain activity in response to stimulation of four brain areas in patients with PD.Methods21 healthy controls and 32 patients with PD underwent a combined TMS-EEG assessment that included stimulation of four brain areas: left M1, right M1, left dorso-lateral prefrontal cortex (DLPFC), and right DLPFC. Six measures were calculated to characterize the TMS evoked potentials (TEP) using EEG: (1) wave form adherence (WFA), (2) late phase deflection (LPD), (3) early phase deflection (EPD), (4) short-term plasticity (STP), (5) inter-trial adherence, and (6) connectivity between right and left M1 and DLPFC. A Linear mixed-model was used to compare these measures between groups and areas stimulated.ResultsPatients with PD showed lower WFA (p = 0.052), lower EPD (p = 0.009), lower inter-trial adherence (p < 0.001), and lower connectivity between homologs areas (p = 0.050), compared to healthy controls. LPD and STP measures were not different between the groups. In addition, lower inter-trial adherence correlated with longer disease duration (r = −0.355, p = 0.050).ConclusionsOur findings provide evidence to various alterations in neurophysiological measures in patients with PD. The higher cortical excitability along with increased variability and lower widespread of the evoked potentials in PD can elucidate different aspects related to the pathophysiology of the disease.     

不同加量调强放疗方案在 Ⅱb～Ⅲb期宫颈癌治疗中的疗效及安全性比较

目的 探讨后程与同期加量调强放疗方案治疗宫颈癌合并盆腔淋巴结转移的疗效及安全性差异。 方法 研究对象选取陕西中医药大学第二附属医院2012年1月至2013年12月收治的宫颈癌合并盆腔淋巴结转移患者共80例,根据随机数字表法分为后程组(40例)和同期组(40例),分别在铂类化疗基础上同步给予后程与同期加量调强放疗方案治疗,比较两组患者近期疗效、中位总生存时间(OS)、无进展生存时间(PFS)、远处转移时间(DMR)、随访复发转移率、危及器官放射剂量及毒副作用发生率等。 结果 同期组近期治疗客观缓解率97.50%显著高于后程组80.00%(χ²=6.135,P<0.05);同期组中位OS、PFS及DMR分别为23.6、16.8、19.1个月,后程组分别为18.3、13.5、15.4个月,同期组均长于后程组(χ²=6.355、3.846、4.859,P<0.05);同期组患者野内淋巴结复发率为5.00%,显著低于后程组22.50%(χ²=5.165,P<0.05);同期组患者小肠最大放射剂量(Dmax)、直肠Dmax及膀胱1cc体积(D1cc)放射剂量分别为(54.73±6.05)Gy、(54.10±5.89)Gy、(54.26±7.18)Gy,后程组分别为(62.12±8.31)Gy、(65.32±7.66)Gy、(68.70±9.53)Gy,同期组均低于后程组(t=4.547、6.166、7.564,P<0.05);同期组患者骨髓抑制发生率35.00%显著低于后程组65.00%(χ²=7.200,P<0.05)。 结论 相较于后程加量方案,同期加量调强放疗方案治疗合并盆腔淋巴结转移宫颈癌可有效控制肿瘤进展,改善远期生存率,避免远期转移,且有助于降低骨髓抑制发生风险。     

深圳市CT医疗照射所致居民剂量负担的研究

目的 了解深圳市CT医疗照射的现状,估计所致居民剂量负担。方法 采用普查方法,对2016年深圳市医疗机构中使用的CT进行调查。首先分头部、胸部、腹部和其他部位调查CT扫描人次和标准扫描参数,结合测量的加权CT剂量指数和文献结果,估算深圳市CT医疗照射所致居民的剂量负担。结果 2016年深圳市CT医疗照射频率为109.84人次/千人口,估算头部、胸部和腹部CT扫描的平均有效剂量分别为1.21 mSv、5.83 mSv和7.08 mSv。2016年深圳市CT医疗照射所致居民集体剂量为6090.28 Sv·人,人均年有效剂量为0.530 mSv。结论 CT医疗照射频率和单次扫描剂量是影响居民剂量负担大小的两个重要因素,减少一切不必要的照射和建立CT医疗照射指导水平是降低集体剂量负担的有效途径。