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Institute
- Klinik und Poliklinik für Strahlentherapie (88) (remove)
Background: To introduce a novel method of patient positioning for high precision intracranial radiotherapy. Methods: An infrared(IR)-array, reproducibly attached to the patient via a vacuum-mouthpiece(vMP) and connected to the table via a 6 degree-of-freedom(DoF) mechanical arm serves as positioning and fixation system. After IR-based manual prepositioning to rough treatment position and fixation of the mechanical arm, a cone-beam CT(CBCT) is performed. A robotic 6 DoF treatment couch (HexaPOD™) then automatically corrects all remaining translations and rotations. This absolute position of infrared markers at the first fraction acts as reference for the following fractions where patients are manually prepositioned to within ± 2 mm and ± 2° of this IR reference position prior to final HexaPOD-based correction; consequently CBCT imaging is only required once at the first treatment fraction. The preclinical feasibility and attainable repositioning accuracy of this method was evaluated on a phantom and human volunteers as was the clinical efficacy on 7 pilot study patients. Results: Phantom and volunteer manual IR-based prepositioning to within ± 2 mm and ± 2° in 6DoF was possible within a mean(± SD) of 90 ± 31 and 56 ± 22 seconds respectively. Mean phantom translational and rotational precision after 6 DoF corrections by the HexaPOD was 0.2 ± 0.2 mm and 0.7 ± 0.8° respectively. For the actual patient collective, the mean 3D vector for inter-treatment repositioning accuracy (n = 102) was 1.6 ± 0.8 mm while intra-fraction movement (n = 110) was 0.6 ± 0.4 mm. Conclusions: This novel semi-automatic 6DoF IR-based system has been shown to compare favourably with existing non-invasive intracranial repeat fixation systems with respect to handling, reproducibility and, more importantly, intrafraction rigidity. Some advantages are full cranial positioning flexibility for single and fractionated IGRT treatments and possibly increased patient comfort.
Background:
The vital importance of imaging techniques in radiation oncology now extends beyond diagnostic evaluation and treatment planning. Recent technical advances have enabled the integration of various imaging modalities into the everyday practice of radiotherapy directly at the linear accelerator, improving the management of inter-and intrafractional variations.
Methods:
We present the topic of image-guided radiotherapy (IGRT) on the basis of a selective review of the literature.
Results:
IGRT can be performed with the aid of ultrasound, 2D X-ray devices, and computed tomography. It enables instant correction for positioning deviations and thereby improves the precision of daily radiotherapy fractions. It also enables immediate adjustment for changes in the position and filling status of the internal organs. Anatomical changes that take place over the course of radiotherapy, such as weight loss, tumor shrinkage, and the opening of atelectases, can be detected as they occur and accounted for in dosimetric calculations. There have not yet been any randomized controlled trials showing that IGRT causes fewer adverse effects or improves tumor control compared to conventional radiotherapy.
Conclusion:
IGRT is more precise and thus potentially safer than conventional radiotherapy. It also enables the application of special radiotherapeutic techniques with narrow safety margins in the vicinity of radiosensitive organs. Proper patient selection for IGRT must take account of the goals of treatment and the planning characteristics, as well as the available technical and human resources. IGRT should be used for steep dose gradients near organs at risk, for highly conformal dose distributions in the gastrointestinal tract where adjustment for filling variations is needed, for high-precision dose escalation to avoid geographic miss, and for patients who cannot lie perfectly still because of pain or claustrophobia.
The majority of breast cancer patients will require radiation therapy at some time during the course of their disease. An estimated 30–50% of all radiation treatments are of palliative nature, either to alleviate symptoms or prophylactic to prevent deterioration of quality of life due to locally progressive disease. Radiotherapy is a locally effective tool, and typically causes no systemic and mostly mild acute side effects. The following article provides an overview of options and decision-making in palliative radiotherapy for symptom control.
Purpose
The purpose of this work is to develop fast deliverable step and shoot IMRT technique. A reduction in the number of segments should theoretically be possible, whilst simultaneously maintaining plan quality, provided that the reduction is accompanied by an increased number of gantry angles. A benefit of this method is that the segment shaping could be performed during gantry motion, thereby reducing the delivery time. The aim was to find classes of such solutions whose plan quality can compete with conventional IMRT.
Materials/Methods
A planning study was performed. Step and shoot IMRT plans were created using direct machine parameter optimization (DMPO) as a reference. DMPO plans were compared to an IMRT variant having only one segment per angle ("2-Step Fast"). 2-Step Fast is based on a geometrical analysis of the topology of the planning target volume (PTV) and the organs at risk (OAR). A prostate/rectum case, spine metastasis/spinal cord, breast/lung and an artificial PTV/OAR combination of the ESTRO-Quasimodo phantom were used for the study. The composite objective value (COV), a quality score, and plan delivery time were compared. The delivery time for the DMPO reference plan and the 2-Step Fast IMRT technique was measured and calculated for two different linacs, a twelve year old Siemens Primus™ ("old" linac) and two Elekta Synergy™ "S" linacs ("new" linacs).
Results
2-Step Fast had comparable or better quality than the reference DMPO plan. The number of segments was smaller than for the reference plan, the number of gantry angles was between 23 and 34. For the modern linac the delivery time was always smaller than that for the reference plan. The calculated (measured) values showed a mean delivery time reduction of 21% (21%) for the new linac, and of 7% (3%) for the old linac compared to the respective DMPO reference plans. For the old linac, the data handling time per beam was the limiting factor for the treatment time reduction.
Conclusions
2-Step Fast plans are suited to reduce the delivery time, especially if the data handling time per beam is short. The plan quality can be retained or even increased for fewer segments provided more gantry angles are used.
Background
Spinal radiosurgery is a quickly evolving technique in the radiotherapy and neurosurgical communities. However, the methods of spine radiosurgery have not been standardized. This article describes the results of a survey about the methods of spine radiosurgery at five international institutions.
Methods
All institutions are members of the Elekta Spine Radiosurgery Research Consortium and have a dedicated research and clinical focus on image-guided radiosurgery. The questionnaire consisted of 75 items covering all major steps of spine radiosurgery.
Results
Strong agreement in the methods of spine radiosurgery was observed. In particular, similarities were observed with safety and quality assurance playing an important role in the methods of all institutions, cooperation between neurosurgeons and radiation oncologists in case selection, dedicated imaging for target- and organ-at-risk delineation, application of proper safety margins for the target volume and organs-at-risk, conformal planning and precise image-guided treatment delivery, and close clinical and radiological follow-up. In contrast, three major areas of uncertainty and disagreement were identified: 1) Indications and contra-indications for spine radiosurgery; 2) treatment dose and fractionation and 3) tolerance dose of the spinal cord.
Conclusions
Results of this study reflect the current practice of spine radiosurgery in large academic centers. Despite close agreement was observed in many steps of spine radiosurgery, further research in form of retrospective and especially prospective studies is required to refine the details of spinal radiosurgery in terms of safety and efficacy.
AIM: To study short dsRNA oligonucleotides (siRNA) as a potent tool for artificially modulating gene expression of N-Myc down regulated gene 1 (NDRG1) gene induced under different physiological conditions (Normoxia and hypoxia) modulating NDRG1 transcription, mRNA stability and translation.
METHODS: A cell line established from a patient with glioblastoma multiforme. Plasmid DNA for transfections was prepared with the Endofree Plasmid Maxi kit. From plates containing 5 x 10(7) cells, nuclear extracts were prepared according to previous protocols. The pSUPER-NDRG1 vectors were designed, two sequences were selected from the human NDRG1 cDNA (5'-GCATTATTGGCATGGGAAC-3' and 5'-ATGCAGAGTAACGTGGAAG-3'. reverse transcription polymerase chain reaction was performed using primers designed using published information on -actin and hypoxia-inducible factor (HIF)-1 mRNA sequences in GenBank. NDRG1 mRNA and protein level expression results under different conditions of hypoxia or reoxygenation were compared to aerobic control conditions using the Mann-Whitney U test. Reoxygenation values were also compared to the NDRG1 levels after 24 h of hypoxia (P < 0.05 was considered significant).
RESULTS: siRNA- and iodoacetate (IAA)-mediated downregulation of NDRG1 mRNA and protein expression in vitro in human glioblastoma cell lines showed a nearly complete inhibition of NDRG1 expression when compared to the results obtained due to the inhibitory role of glycolysis inhibitor IAA. Hypoxia responsive elements bound by nuclear HIF-1 in human glioblastoma cells in vitro under different oxygenation conditions and the clearly enhanced binding of nuclear extracts from glioblastoma cell samples exposed to extreme hypoxic conditions confirmed the HIF-1 Western blotting results.
CONCLUSION: NDRG1 represents an additional diagnostic marker for brain tumor detection, due to the role of hypoxia in regulating this gene, and it can represent a potential target for tumor treatment in human glioblastoma. The siRNA method can represent an elegant alternative to modulate the expression of the hypoxia induced NDRG1 gene and can help to monitor the development of the cancer disease treatment outcome through monitoring the expression of this gene in the patients undergoing the different therapeutic treatment alternatives available nowadays.
Background: Adaptive Radiotherapy aims to identify anatomical deviations during a radiotherapy course and modify the treatment plan to maintain treatment objectives. This requires regions of interest (ROIs) to be defined using the most recent imaging data. This study investigates the clinical utility of using deformable image registration (DIR) to automatically propagate ROIs.
Methods: Target (GTV) and organ-at-risk (OAR) ROIs were non-rigidly propagated from a planning CT scan to a per-treatment CT scan for 22 patients. Propagated ROIs were quantitatively compared with expert physician-drawn ROIs on the per-treatment scan using Dice scores and mean slicewise Hausdorff distances, and center of mass distances for GTVs. The propagated ROIs were qualitatively examined by experts and scored based on their clinical utility.
Results: Good agreement between the DIR-propagated ROIs and expert-drawn ROIs was observed based on the metrics used. 94% of all ROIs generated using DIR were scored as being clinically useful, requiring minimal or no edits. However, 27% (12/44) of the GTVs required major edits.
Conclusion: DIR was successfully used on 22 patients to propagate target and OAR structures for ART with good anatomical agreement for OARs. It is recommended that propagated target structures be thoroughly reviewed by the treating physician.
Background: Recently published results of quality of life (QoL) studies indicated different outcomes of palliative radiotherapy for brain metastases. This prospective multi-center QoL study of patients with brain metastases was designed to investigate which QoL domains improve or worsen after palliative radiotherapy and which might provide prognostic information.
Methods: From 01/2007-01/2009, n=151 patients with previously untreated brain metastases were recruited at 14 centers in Germany and Austria. Most patients (82 %) received whole-brain radiotherapy. QoL was measured with the EORTC-QLQ-C15-PAL and brain module BN20 before the start of radiotherapy and after 3 months.
Results: At 3 months, 88/142 (62 %) survived. Nine patients were not able to be followed up. 62 patients (70.5 % of 3-month survivors) completed the second set of questionnaires. Three months after the start of radiotherapy QoL deteriorated significantly in the areas of global QoL, physical function, fatigue, nausea, pain, appetite loss, hair loss, drowsiness, motor dysfunction, communication deficit and weakness of legs. Although the use of corticosteroid at 3 months could be reduced compared to pre-treatment (63 % vs. 37 %), the score for headaches remained stable. Initial QoL at the start of treatment was better in those alive than in those deceased at 3 months, significantly for physical function, motor dysfunction and the symptom scales fatigue, pain, appetite loss and weakness of legs. In a multivariate model, lower Karnofsky performance score, higher age and higher pain ratings before radiotherapy were prognostic of 3-month survival.
Conclusions: Moderate deterioration in several QoL domains was predominantly observed three months after start of palliative radiotherapy for brain metastases. Future studies will need to address the individual subjective benefit or burden from such treatment. Baseline QoL scores before palliative radiotherapy for brain metastases may contain prognostic information.
Background: Ga-[1,4,7,10-tetraazacyclododecane-N,N0,N00,N000-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE) positron emission tomography (PET) is commonly used for the visualization of somatostatin receptor (SSTR)-positive neuroendocrine tumors. SSTR is also known to be expressed on macrophages, which play a major role in inflammatory processes in the walls of coronary arteries and large vessels. Therefore, imaging SSTR expression has the potential to visualize vulnerable plaques. We assessed 68Ga-DOTATATE accumulation in large vessels in comparison to 18F-2-fluorodeoxyglucose (FDG) uptake, calcified plaques (CPs), and cardiovascular risk factors. Methods: Sixteen consecutive patients with neuroendocrine tumors or thyroid cancer underwent both 68Ga-DOTATATE and 18F-FDG PET/CT for staging or restaging purposes. Detailed clinical data, including common cardiovascular risk factors, were recorded. For a separate assessment, they were divided into a high-risk and a low-risk group. In each patient, we calculated the maximum target-to-background ratio (TBR) of eight arterial segments. The correlation of the TBRmean of both tracers with risk factors including plaque burden was assessed. Results: The mean TBR of 68Ga-DOTATATE in all large arteries correlated significantly with the presence of CPs (r = 0.52; p < 0.05), hypertension (r = 0.60; p < 0.05), age (r = 0.56; p < 0.05), and uptake of 18F-FDG (r = 0.64; p < 0.01). There was one significant correlation between 18F-FDG uptake and hypertension (0.58; p < 0.05). Out of the 37 sites with the highest focal 68Ga-DOTATATE uptake, 16 (43.2%) also had focal 18F-FDG uptake. Of 39 sites with the highest 18F-FDG uptake, only 11 (28.2%) had a colocalized 68Ga-DOTATATE accumulation. Conclusions: In this series of cancer patients, we found a stronger association of increased 68Ga-DOTATATE uptake with known risk factors of cardiovascular disease as compared to 18F-FDG, suggesting a potential role for plaque imaging in large arteries. Strikingly, we found that focal uptake of 68Ga-DOTATATE and 18F-FDG does not colocalize in a significant number of lesions.
Background: To analyze the accuracy and inter-observer variability of image-guidance (IG) using 3D or 4D cone-beam CT (CBCT) technology in stereotactic body radiotherapy (SBRT) for lung tumors. Materials and methods: Twenty-one consecutive patients treated with image-guided SBRT for primary and secondary lung tumors were basis for this study. A respiration correlated 4D-CT and planning contours served as reference for all IG techniques. Three IG techniques were performed independently by three radiation oncologists (ROs) and three radiotherapy technicians (RTTs). Image-guidance using respiration correlated 4D-CBCT (IG-4D) with automatic registration of the planning 4D-CT and the verification 4D-CBCT was considered gold-standard. Results were compared with two IG techniques using 3D-CBCT: 1) manual registration of the planning internal target volume (ITV) contour and the motion blurred tumor in the 3D-CBCT (IG-ITV); 2) automatic registration of the planning reference CT image and the verification 3D-CBCT (IG-3D). Image quality of 3D-CBCT and 4D-CBCT images was scored on a scale of 1–3, with 1 being best and 3 being worst quality for visual verification of the IGRT results. Results: Image quality was scored significantly worse for 3D-CBCT compared to 4D-CBCT: the worst score of 3 was given in 19 % and 7.1 % observations, respectively. Significant differences in target localization were observed between 4D-CBCT and 3D-CBCT based IG: compared to the reference of IG-4D, tumor positions differed by 1.9 mm± 0.9 mm (3D vector) on average using IG-ITV and by 3.6 mm± 3.2 mm using IG-3D; results of IG-ITV were significantly closer to the reference IG-4D compared to IG-3D. Differences between the 4D-CBCT and 3D-CBCT techniques increased significantly with larger motion amplitude of the tumor; analogously, differences increased with worse 3D-CBCT image quality scores. Inter-observer variability was largest in SI direction and was significantly larger in IG using 3D-CBCT compared to 4D-CBCT: 0.6 mm versus 1.5 mm (one standard deviation). Inter-observer variability was not different between the three ROs compared to the three RTTs. Conclusions: Respiration correlated 4D-CBCT improves the accuracy of image-guidance by more precise target localization in the presence of breathing induced target motion and by reduced inter-observer variability.