Verbesserte Lagerungsreproduzierbarkeit eines nichtinvasiven Hochpräzisionsmaskensystems in der stereotaktischen Radiotherapie durch eine integrierte Kieferfixierung

BACKGROUND: For high precision radiotherapy of the neurocranium a precise, reproducible positioning technique is the basic prerequisite. The aim of this study was to assess the influence of a modification of the commercially available stereotactical BrainLab-head mask system on accuracy in patient positioning during fractionated radiotherapy. MATERIAL AND METHODS: 29 patients were treated with stereotactic radiotherapy of the head. Immobilization was provided by a two layer thermoplastic mask system (BrainLab). 18 of these patients received an additional custom made fixation either of the upper jaw (OKF) or of the mandibula (UKF). The positioning accuracy was assessed by measurements of the shifting of anatomical landmarks in relation to the rigid mask system on biplanar simulator films using a digital imaging system. Before each measurement a fine adjustment of the simulator to an optical ring system was performed. The reference radiographs were done just before CT-planning. During a 2-7 weeks lasting course of radiotherapy displacement measurements in relation to the reference images for all three dimensions (z, y and x) were done once a week. In 29 patients 844 measurements were analyzed. RESULTS: An additional jaw fixation improves the reproducibility of patient positioning significantly in all three spatial dimensions. The standard deviation in lateral direction (x) was 0.6 mm with jaw fixation vs. 0.7 mm without jaw fixation (p < 0.001); in longitudinal direction (z) (measured in 0 degree radiographs) 0.5 mm vs. 1.3 mm (p < 0.001); in longitudinal direction (measured in 90 degrees radiographs) 0.5 mm vs. 1.5 mm (p < 0.001); in vertical direction (y) 0.6 mm vs. 0.9 mm (p = 0.001). No significant differences in standard deviations were found comparing OKF (n = 14) with UKF (n = 4). CONCLUSION: A significant improvement in reposition accuracy using an additional, individually formed jaw fixation can be acquired. The variability of positioning can be reduced especially in the z-direction. A further reduction of the safety margin around the target volume--especially in benign tumors--is possible by improved fixation technique.     

Epigenetic regulation mechanism of ABCG2 induced drug-resistant phenotype

The aim of this study is to investigate epigenetic mechanism of ABCG2 induced drug-resistance.It is not only expatiate for drug-resistance regulation mechanism in all-round,but also to provide scientific experimental basis for selecting target to reverse its drug-resistance.Apply methylation-specific PCR (MSP) to have tested methylation of ABCG2 promoter region -359 to -353 specific positions in breast cancer tissues and paired adjacent tissue of 22 cases,and test their methylation positions with MSP products for sequencing; and adopt fluorescent quantitation RT-PCR to test expression level DNMT1,DNMT3A,DNMT3B and ABCG2; to make analysis on relationship between them with statistical spearman correlation.Specific positions of ABCG2 gene promoter region of 18 cases among the 22 cases with breast cancer (18/22,82％) existed high methylation (P＜0.05),MSP products sequencing proved methylation of the specific position,and mRNA expression level was relative higher in remarkable positive correlation (P＜0.05).ABCG2,DNMT1,DNMT3A,DNMT3B mRNA expression levels in breast cancer tissues were obviously higher than adjacent tissues (P＜0.01),and DNMT3B expression level was obviously higher than DNMT1 and DNMT3A (P＜0.01)in negative correlation with ABCG2 gene expression (P-0.001).-359 to -353 positions of promoter regions of ABCG2 gene existed high methylation capable to push expression of this gene in beast cancer tissue.DNMT3B is involved in expression regulation in ABCG2 gene,and provides new scientific basis tor drug-resistance target as reverse ABCG2 induction.     

Investigations of peripheral dose for helical tomotherapy

PurposeWhenever treating a patient with percutaneous radiotherapy, a certain amount of dose is inevitably delivered to healthy tissue. This is mainly due to beam's entry and exit in the region of the target volume. In regions distant from the target volume, dose is delivered by leakage from the MLC and head scatter from the accelerator head and phantom scatter from the target volume (peripheral dose). Helical tomotherapy is a form of radiation therapy with a uniquely designed machine and delivery pattern which influence the peripheral dose. The goal of this work was to investigate peripheral dose in helical tomotherapy. The experiments were used to establish a complex characterization of the peripheral dose.Materials and methodsA 30*30*60cm³ slab phantom and TLD-100 (Lithium fluoride) were used for the experiments. Treatment procedures were generated with the tomotherapy planning system (TPS). Additionally, procedures were created on the Operator Station of the tomotherapy system without a calculation of the dose distribution. The peripheral dose which was produced by a typical tomotherapy treatment plan was measured. Furthermore, these procedures were used to differentiate the parts of the peripheral dose in phantom scatter dose and head scatter and leakage dose. Additionally, the relation between peripheral dose and treatment time and between peripheral dose and delivered dose was investigated. Additionally, the peripheral dose was measured in an Alderson phantom.ResultsDistances of 30cm or more resulted in a decrease of the peripheral dose to less than 0.1% of the target dose. The measured doses have an offset of approximately 1cGy in comparison to the calculated doses from the TPS. The separated head scatter and leakage dose was measured in the range of 1cGy for typical treatments. Furthermore, the investigations show a linear correlation between head scatter leakage dose and treatment time and between scatter dose parts and delivered dose. A peripheral dose of 0.28% of the target dose was measured in the Alderson phantom at a distance of 17.5cm from the edge of the target volume.ConclusionsThe peripheral dose delivered by a tomotherapy treatment is clinically unobjectionable. The measurements confirmed a linear correlation between head scatter and leakage and treatment time and between scatter dose and delivered dose.     

Dosimetry of a linear accelerator under respiratory gating

In the present study, the impact of respiratory gating on the beam characteristics of a linear accelerator is investigated. The main focus is put on the influence of the duty cycle. Measurements were performed on a linear accelerator type Oncor (Siemens) with photon energies 6 MV and 15 MV, equipped with the Anzai gating system AZ-733V. Depth dose curves and beam profiles were found not to be significantly altered by gating even for duty cycles down to 5% for realistic respiration frequencies (dose variations all <2.5%). However, for very small duty cycles, the absolute dosimetry changes significantly (dose deviations >10%), leading to clinically relevant underdoses. The crucial parameter for the dosimetry is the number of monitor units per gate. Our results imply that treatment planning for respiratory gating can be performed on the basis of data obtained under ungated operation if and only if the absolute gates sizes during treatment are sufficiently large. The limiting values for the gate sizes have to be determined individually for each accelerator.     

A Q-TWiST analysis comparing panitumumab plus best supportive care (BSC) with BSC alone in patients with wild-type KRAS metastatic colorectal cancer

Background:

Panitumumab+best supportive care (BSC) significantly improved progression-free survival (PFS) vs BSC alone in patients with chemo-refractory wild-type KRAS metastatic colorectal cancer (mCRC). We applied the quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) analysis to provide an integrated measure of clinical benefit, with the objective of comparing quality-adjusted survival between the two arms. As the trial design allowed patients on BSC alone to receive panitumumab after disease progression, which confounded overall survival (OS), the focus of this analysis was on PFS.

Methods:

For each treatment group, the time spent in the toxicity (grade 3 or 4 adverse events; TOX), time without symptoms of disease or toxicity (TWiST), and relapse (after disease progression; REL) states were estimated by the product-limit method, and adjusted using utility weights derived from patient-reported EuroQoL 5-dimensions measures. Sensitivity analyses were performed in which utility weights (varying from 0 to 1) were applied to time in the TOX and REL health states.

Results:

There was a significant difference between groups favouring panitumumab+BSC in quality-adjusted PFS (12.3 weeks vs 5.8 weeks, respectively, P<0.0001) and quality-adjusted OS (P=0.0303).

Conclusion:

In patients with chemo-refractory wild-type KRAS mCRC, panitumumab+BSC significantly improved quality-adjusted survival compared with BSC alone.     

Experimental determination of peripheral photon dose components for different IMRT techniques and linear accelerators

PurposeTo quantify the relative peripheral photon doses (PD) to healthy tissues outside the treated region for different IMRT technologies and linac head designs.Material and MethodsMeasurements were performed on an Elekta linac for various energies (6 MV, 10 MV, 25 MV) at different depths at a distance of 29 cm off-axis (vertical measurements) and different distances from the field edge at constant depth of 10 cm (horizontal measurements). These measurements were compared with results obtained on a Siemens linac at 6 MV and 15 MV [26]. TLD-700 detectors were used to quantify the PDs relative to the dose in the volume exposed with the primary beam. Intensity modulated (IM)-beams with identical fluence patterns were generated with a segmental multileaf (sMLC) technique and with lead-containing cerrobend compensators (MCP96). PD values of IM beams were compared with open beam values. All measurement results of the two different linacs, the different IM methods and the different energies were normalized to the same mean dose.ResultsPD values were distinctly higher near the surface (0.5–20 mm) than at larger depth and showed the same trend for all photon beam energies. In comparison with the open field, the photon dose component of PD for IM beams delivered with a segmental MLC technique were increased by a factor varying from 1.2 to 1.8, depending on photon energy and depth. This ratio was around 2 for compensator based IMRT. Depending on depth and distance from the field edge the PD on the Siemens machine was about 30% to 50% higher than on the Elekta machine for the same nominal photon energy.ConclusionThe treatment head design of a linac has a large impact on PD in IMRT as well as for open beams. PD can be minimized by proper selection of treatment delivery method and photon beam energy.     

VERIDOS: A New Tool for Quality Assurance for Intensity Modulated Radiotherapy

BACKGROUND: The use of intensity modulated radiation fields needs an extended quality assurance concept. This consists of a linac related part and a case related part. Case related means the verification of an individual treatment plan, optimized on a CT data set of an individual patient and prepared for the treatment of this patient. This part of the quality assurance work is usually time consuming, delivers only partially quantitative results and is uncomfortable without additional help. It will be shown in this paper how the software VERIDOS will improve the optimization of the case related part of the quality assurance work. MATERIAL AND METHODS: The main function of the software is the quantitative comparison of the calculated dose distribution from the treatment planning software with the measured dose distribution of an irradiated phantom. Several additional functions will be explained. Two self-developed phantoms made of RW3 (solid water) and GAFCHROMIC films or Kodak EDR2 films for the measurement of the dose distributions were used. VERIDOS was tested with the treatment planning systems Helay-TMS and Brainscan. RESULTS: VERIDOS is a suitable tool for the import of calculated dose matrices from the treatment planning systems Helax-TMS and Brainscan and of measured dose matrices exported from the dosimetry software Mephysto (PTW). The import from other treatment planning systems and scanning software applications for film dosimetry is generally possible. In such case the import function has to be adapted to the special header of the import matrix. All other functions of this software tool like normalization (automatically, manually), working with corrections (ground substraction, factors), overlay/comparison of dose distributions, difference matrix, cutting function (profiles) and export functions work reliable. CONCLUSIONS: VERIDOS improves the optimization of the case related part of the quality assurance work for intensity modulated radiation therapy (IMRT). The diverse functions of the software offer the radiation physicist a wide base to verify the IMRT plan independent from the mode of its delivery (compensator technology or MLC technology).     

4-氨基吡啶诱发组胺释放及某些药物的拮抗作用

4-氨基吡啶(4-AP)有组胺释放作用。小鼠ip4-AP5mg·kg^-1后,肺中组胺含量明显减低,血中组胺含量显著增高。钙拮抗剂硝苯啶、TMB-8及钾通道开放剂米诺地尔均能明显抑制4-AP诱发的小鼠PMC释放组胺。结果提示,MC可能存在钾通道,4-AP诱发MC释放组胺可能与它阻滞钾通道,从而使钙通道开放,增加Ca²⁺内流有关。