Stereotactic radiosurgery utilizing a linear accelerator

The authors have developed a radiosurgical technique based on multiple arc irradiations. The target is fixed to the rotational isocenter of a Varian 4 MV linear accelerator. The first irradiation is carried out while the radiating source is rotating on a 100-140 degrees arc. The patient is then rotated around a vertical axis passing through the target, and arc irradiations are repeated in different angular positions. By this technique it is possible to obtain very steep dose gradients at the borders of the target volume. High doses are usually delivered in two shots. 47 patients have been treated so far in a clinical trial that started in November 1982. The paper deals with the preliminary results (more than 6 months' follow-up) obtained in patients affected by nonresectable brain tumors and AVMs.     

Development of a phantom for dose distribution verification in Stereotactic Radiosurgery

A geometric acrylic phantom was designed and built for dose distribution verification in Stereotactic Radiosurgery. Acrylic objects representing the tumor tissue, (target volume (TV)), and the organ at risk (OAR), the brainstem, were inserted inside this phantom. The TV is represented by two semi-spheres of acrylic with a diameter of 13.0 mm, both having a central cavity for accommodation of a TLD-100 detector and a small radiochromic Gafchromic EBT film. The OAR is represented by the two parts of a 38.0 mm length acrylic cylinder with a diameter 18.0 mm and cavities along the cylinder central axis able to accommodate 5 TLD – 100 detectors and another of EBT film between the two cylinder parts. This experimental setup was submitted to a radiosurgical treatment, after which the TL dosimeters were evaluated and their responses were compared with the planned dose values. The radiochromic EBT films showed the dose distributions. The linear accelerator used was a Varian 2300 C/D, generating a 6 MV photon beam. The investigated phantom system was able to check the accuracy of dose delivery to predetermined points and the dose distribution due to stereotactic radiosurgery treatments and proved to be a good tool for quality control in these situations.     

Spot-scanned pancreatic stereotactic body proton therapy: A dosimetric feasibility and robustness study

PurposeWe explored the dosimetric potential of spot-scanned stereotactic body proton therapy (SBPT) for pancreatic cancer.MethodsWe compared SBPT to stereotactic body intensity-modulated radiotherapy (SB-IMRT) in 10 patients. We evaluated 3 variables in SBPT planning: (1) 4 and 6 mm spot size; (2) single vs. multi-field optimization (SFO vs. MFO); and (3) optimization target volume (OTV) expansion. Robustness analysis was performed with unidirectional isocenter shifts of ±3 mm in x, y, and z and ±3% stopping power uncertainties.ResultsSBPT plans had lower V_10Gy for the stomach and small and large bowels. Under static robustness, a 5 mm OTV and SFO-6 mm spot size represented the best compromise between target and normal structure. A 4-mm spot-size and 3 mm OTV resulted in significant target underdosing with deformable dose accumulation analysis.ConclusionsThis study provides a critical basis for clinical translation of spot size, optimization technique, and OTV expansion for pancreatic SBPT.     

Proton or photon radiosurgery for cardiac ablation of ventricular tachycardia? Breath and ECG gated robust optimization

PurposeVentricular tachycardia (VT) is a life-threatening heart disorder. The aim of this preliminary study is to assess the feasibility of stereotactic body radiation therapy (SBRT) photon and proton therapy (PT) plans for the treatment of VT, adopting robust optimization technique for both irradiation techniques.MethodsECG gated CT images (in breath hold) were acquired for one patient. Conventional planning target volume (PTV) and robust optimized plans (25GyE in single fraction) were simulated for both photon (IMRT, 5 and 9 beams) and proton (SFO, 2 beams) plans. Robust optimized plans were obtained both for protons and photons considering in the optimization setup errors (5 mm in the three orthogonal directions), range (±3.5%) and the clinical target volume (CTV) motion due to heartbeat and breath-hold variability.ResultsThe photon robust optimization method, compared to PTV-based plans, showed a reduction in the average dose to the heart by about 25%; robust optimization allowed also reducing the mean dose to the left lung from 3.4. to 2.8 Gy for 9-beams configuration and from 4.1 to 2.9 Gy for 5-beams configuration. Robust optimization with protons, allowed further reducing the OAR doses: average dose to the heart and to the left lung decreased from 7.3 Gy to 5.2 GyE and from 2.9 Gy to 2.2 GyE, respectively.ConclusionsOur study demonstrates the importance of the optimization technique adopted in the treatment planning system for VT treatment. It has been shown that robust optimization can significantly reduce the dose to healthy cardiac tissues and that PT further increases this gain.     

陀螺旋转式伽玛刀分次治疗颅内转移瘤的临床疗效观察

目的:评价大分割伽玛射线立体定向放射治疗对颅内转移瘤的临床疗效.方法:采用陀螺旋转式伽玛射线立体定向放射设备治疗颅内转移瘤患者91例.单纯伽玛射线立体定向放射治疗采取大分割分次方式,处方剂量3.2-5Gy,每周5次,计划靶区边缘(45％或65％等剂量线处)总剂量全程为35-50Gy.结果:近期有效率(CR+PR)颅内移瘤少于3个组为93.06％ (67/72),大于3个组为73.69％ (14/19);局部剂量与肿瘤复发的关系,照射剂量50GY者复发率为11.86％(7/59),照射剂量为40GY者复发率为31.25％(10/32);生存率陀螺刀治疗的中位生存期为11.9个月.6、12、24个月生存率分别为:76.92％ (70/91)、60.44％(55/91)、29.67％(27/91).结论:大分割伽玛射线立体定向放射治疗脑部和体部恶性肿瘤近期疗效满意.     

Investigation of the in vitro therapeutic efficacy of nilotinib in immortalized human NF2-null vestibular schwannoma cells

Vestibular schwannomas (VS) are a common posterior fossa brain tumor, and though benign can cause significant morbidity, particularly loss of hearing, tinnitus, vertigo and facial paralysis. The current treatment options for VS include microsurgical resection, stereotactic radiosurgery or close surveillance monitoring, with each treatment option carrying associated complications and morbidities. Most importantly, none of these options can definitively reverse hearing loss or tinnitus. Identification of a novel medical therapy, through the use of targeted molecular inhibition, is therefore a highly desirable treatment strategy that may minimize complications arising from both tumor and treatment and more importantly be suitable for patients whose options are limited with respect to surgical or radiosurgical interventions. In this study we chose to examine the effect of Nilotinib on VS. Nilotinib (Tasigna?) is a second-generation receptor tyrosine kinase (RTK) inhibitor with a target profile similar to that of imatinib (Gleevec?), but increased potency, decreased toxicity and greater cellular and tissue penetration. Nilotinib targets not only the BCR-ABL oncoprotein, but also platelet-derived growth factor (PDGF) receptor signalling. In this preclinical study, the human NF2-null schwannoma cell line HEI-193 subjected to nilotinib inhibition demonstrated decreased viability, proliferation and anchorage-independent growth, and increased apoptosis. A daily dose of nilotinib for 5 days inhibited HEI-I93 proliferation at a clinically-relevant concentration in a dose-dependent manner (IC(50) 3-5 μmol/L) in PDGF-stimulated cells. These anti-tumorigenic effects of nilotinib were correlated to inhibited activation of PDGFR-α and PDGFR-β and major downstream signalling pathways. These experiments support a therapeutic potential for Nilotinib in VS.     

Stereotactic radiotherapy for oligometastases in the lymph nodes

Even though systemic therapy is standard treatment for lymph node metastases, metastasis-directed stereotactic radiotherapy (SRT ) seems to be a valid option in oligometastatic patients with a low disease burden.Positron emission tomography-computed tomography (PET-CT ) is the gold standard for assessing metastases to the lymph nodes; co-registration of PET-CT images and planning CT images are the basis for gross tumor volume (GTV ) delineation. Appropriate techniques are needed to overcome target motion. SRT schedules depend on the irradiation site, target volume and dose constraints to the organs at risk (OARs) of toxicity. Although several fractionation schemes were reported, total doses of 48–60 Gy in 4–8 fractions were proposed for mediastinal lymph node SRT, with the spinal cord, esophagus, heart and proximal bronchial tree being the dose limiting OAR s. Total doses ranged from 30 to 45 Gy, with daily fractions of 7–12 Gy for abdominal lymph nodes, with dose limiting OARs being the liver, kidneys, bowel and bladder. SRT on lymph node metastases is safe; late side effects, particularly severe, are rare.     

Dosimetry of total skin electron irradiation

Elaboration of such a simple technique for total skin electron irradiation which ensures good dose homogeneity and minimal x-ray background dose. MATERIALS AND METHODS: We started large electron field irradiations with the Neptun 10p linear accelerator in the National Institute of Oncology -Budapest in 1986. After the installation of the Siemens Mevatron KD linear accelerator it was possible to introduce the modified Stanford technique. This technique satisfies better the requirements given in the objective. The required field size of 200x75 cm is produced as a result of two fields with 30 degrees angular separation (dual field) at a source skin distance of 465 cm. The patient's body is exposed to six dual electron fields. The electron energy is 6 MeV. Despite the long source skin distance the treatment time is relatively short due to the high dose rate (940 mu/min) capability of our Mevatron KD. The in air dose profiles were measured in miniphantom with semiconductor detector. Depth dose curves were measured in water and in polystyrene phantom with semiconductor detector and with films. RESULTS: The measured dose homogeneity of the 6 MeV energy dual field with 30 degrees angular separation is within +/- 5%in a 200x75cm plane field. The depth of dose maximum of the resulting dose distribution of six dual field irradiation is between 2 mm and 5 mm, while the depth of 80% isodose curve is about 8 mm. The total body x-ray background dose is less than 1% of the skin dose. CONCLUSION: The modified Stanford technique adapted to our Mevatron KD linear accelerator is suitable for total skin electron beam therapy.     

An applicability study on a CT-guided stereotactic technique for functional neurosurgery

When a CT-guided stereotactic technique for functional neurosurgery is adopted, extremely precise targeting is needed to obtain satisfactory surgical results. In this study the authors have investigated the accuracy of the target points determined by CT-guided techniques and compared with those of conventional roentgenographically controlled stereotactic procedures. Stereotactic surgery, employing the Brown-Roberts-Wells (BRW) system, was performed contemporarily 26 times in 23 patients, that is, 9 times in 8 patients for functional neurosurgery using with the roentgenographic method, and 17 times in 15 patients with the CT-guided method only for intracranial neoplasm biopsy. As a result, there were no problems of accuracy of determining the target points by CT-guided stereotactic surgery with the BRW system. When applying this technique for functional neurosurgery, it should be pointed out that there could be a discrepancy within 2 mm from the conventional target determination.     

Conformal stereotactic radiosurgery therapy: plan evaluation methods and results

The purpose of our study was the objective evaluation of micro-multileaf collimator (mMLC)-based stereotactic radiosurgery treatment plans. Forty-seven patients, 71 lesions received static beam conformal stereotactic radiosurgery treatment in our institute between November 2005 and June 2008. Target volume and organs at risk were outlined on a MRI-CT image fusion basis. BrainSCAN 5.31 system (BrainLAB AG, Heimstetten, Germany) was used for treatment planning, Elekta Presice TS linear accelerator (Elekta Oncology Systems Ltd, Crawley, UK) and BrainLAB m3 mMLC were used for treatment delivery. An invasive head frame, mounted to the treatment table, was used with four screws for patient head fixation. Treatment plans were analysed with objective parameters, such as conformal index (COIN), homogeneity index (HI), coverage index (CI) and healthy tissue relative overdose factor (HTOF) tools. x2 tests were performed between COIN, HI and the geometrical parameters of the target volume (lesion volume - LV, lesion-organ distance - LOD, lesion deformity index - LDI). Mean value of COIN, HI, HTOF and CI was 0.52 (SD 0.13), 1.16 (SD 0.1), 0.88 (SD 0.53), and 0.94 (SD 0.11), respectively. COIN significantly correlated with (p<0.001 in all three cases), while HI was independent of LV, LOD, LDI (p=0.94; 0.14 and 0.72). COIN is similar, HTOF is less than data from the literature. According to our results geometrical parameters of the target volume (size, location, deformation) significantly influence the COIN, but they have no effect on HI.     

High-Precision Radiosurgical Dose Delivery by Interlaced Microbeam Arrays of High-Flux Low-Energy Synchrotron X-Rays

Microbeam Radiation Therapy (MRT) is a preclinical form of radiosurgery dedicated to brain tumor treatment. It uses micrometer-wide synchrotron-generated X-ray beams on the basis of spatial beam fractionation. Due to the radioresistance of normal brain vasculature to MRT, a continuous blood supply can be maintained which would in part explain the surprising tolerance of normal tissues to very high radiation doses (hundreds of Gy). Based on this well described normal tissue sparing effect of microplanar beams, we developed a new irradiation geometry which allows the delivery of a high uniform dose deposition at a given brain target whereas surrounding normal tissues are irradiated by well tolerated parallel microbeams only. Normal rat brains were exposed to 4 focally interlaced arrays of 10 microplanar beams (52 µm wide, spaced 200 µm on-center, 50 to 350 keV in energy range), targeted from 4 different ports, with a peak entrance dose of 200Gy each, to deliver an homogenous dose to a target volume of 7 mm³ in the caudate nucleus. Magnetic resonance imaging follow-up of rats showed a highly localized increase in blood vessel permeability, starting 1 week after irradiation. Contrast agent diffusion was confined to the target volume and was still observed 1 month after irradiation, along with histopathological changes, including damaged blood vessels. No changes in vessel permeability were detected in the normal brain tissue surrounding the target. The interlacing radiation-induced reduction of spontaneous seizures of epileptic rats illustrated the potential pre-clinical applications of this new irradiation geometry. Finally, Monte Carlo simulations performed on a human-sized head phantom suggested that synchrotron photons can be used for human radiosurgical applications. Our data show that interlaced microbeam irradiation allows a high homogeneous dose deposition in a brain target and leads to a confined tissue necrosis while sparing surrounding tissues. The use of synchrotron-generated X-rays enables delivery of high doses for destruction of small focal regions in human brains, with sharper dose fall-offs than those described in any other conventional radiation therapy.     

A new evaluation method of target volume coverage and homogeneity for IMRT treatment planning

Based on the functional approximation of a target volume DVH (TV-DVH) to a modified step function, we propose a new index that indicates the degrees of dose coverage and homogeneity for target volume reached in clinical routines. Forty-seven IMRT patient plans are included in the analysis to explore the efficiency of the proposed method. The new index, named s-index, was defined to vary from 0:05 for clinically acceptable TV-DVH at our institution and showed the ability to give the user an idea whether the degree of dose coverage and homogeneity for target volume were adequate when the user-defined criteria had been in place. The result shows that the lower value of s-index indecates the higher dose coverage for the tumor volume and/or the higher dose homogeneity showing the faster fall-off rate at the percentage dose higher than 100%. In addition to the quantification of dose coverage and homogeneity is has been also shown that s-index is more accurate in evaluating the dose homogeneity in tumor volume than the conventional method. The proposed method has demonstrated the effectiveness in evaluating TV-DVH in terms of simple index and supplements currently used indices by providing complete information of a DVH curve in a treatment plan.     

Inter-Fraction Tumor Volume Response during Lung Stereotactic Body Radiation Therapy Correlated to Patient Variables

PurposeAnalyze inter-fraction volumetric changes of lung tumors treated with stereotactic body radiation therapy (SBRT) and determine if the volume changes during treatment can be predicted and thus considered in treatment planning.ResultsAll tumors studied experienced volume change during treatment. Tumor increased in volume by an average of 15% and regressed by an average of 11%. The overall volume increase during treatment is contained within the planning target volume (PTV) for all tumors. Larger tumors increased in volume more than smaller tumors during treatment (q = 0.0029). The volume increase on CBCT was correlated to the treatment planning gross target volume (GTV) as well as internal target volumes (ITV) (q = 0.0085 and q = 0.0039 respectively) and could be predicted for tumors with a GTV less than 22 mL. The volume increase was correlated to the integral dose (ID) in the ITV at every fraction (q = 0.0049). The peak inter-fraction volume occurred at an earlier fraction in younger patients (q = 0.0122).ConclusionsWe introduced a new analysis method to follow inter-fraction tumor volume changes and determined that the observed changes during lung SBRT treatment are correlated to the initial tumor volume, integral dose (ID), and patient age. Furthermore, the volume increase during treatment of tumors less than 22mL can be predicted during treatment planning. The volume increase remained significantly less than the overall PTV expansion, and radiation re-planning was therefore not required for the purpose of tumor control. The presence of the studied correlations suggests that the observed volumetric changes may reflect some underlying biologic process rather than random fluctuations.     

Effect of radiation and freezing on [3H]DNA of Yersinia enterocolitica.

Freezing of the enteropathogenic bacterium Yersinia enterocolitica to -18 and -75 degrees C caused 7 and 42% cell death, respectively, and 0.329 and 0.588 single-strand breaks per 10(8) daltons of DNA, respectively, while radiation to one D10 dose (10% cell survival) combined with freezing to 2 to 0, -18, and -75 degrees C induced 0.05, 0.75, and 5.04 single-strand breaks, respectively. The increase in the effectiveness of radiation with respect to the yield of single-strand breaks at -18 and -75 degrees C is contrary to expectation and seems to be due to arrest of repair of single-strand breaks by these low temperatures.     

New diagnostic and therapeutic tools in stereotaxy

A definitive pathoanatomic diagnosis was achieved in 14 biopsies of deep cerebral tumors in which the Laitinen CT adapter was utilized. In 5 patients, a third-ventricular colloid cyst was aspirated or resected by stereotactic endoscopy, with excellent results after a mean follow-up time of 2.5 years. Several instruments, including a diagnostic ultrasound probe, an ultrasonic aspirator, a combination laser and an endoscope can be used stereotactically when mounted on a special instrument carrier. Integration of the Laitinen stereotactic device and the CT adapter was developed to allow noninvasive stereotactic radiotherapy in a conventional fractionation schedule by a standard linear accelerator. Technical experiences using this radiosurgical system in over 30 sessions for treating inoperable cerebral arteriovenous malformations are promising, but the follow-up time is too short for evaluating the clinical effect.     

Olminska and colleagues’ study, “Conversion of the helical tomotherapy plans to the step-and-shoot IMRT plans for patients with hip prosthesis during radiotherapy for prostate cancer” was interesting to read

Olmińska and colleagues’ study, Olmińska et al. (2016) was interesting to read [1]. While prasining the authors for their great work, I want to emphasize e few points.In the recent years, with the development of new device technology, Intensity Modulated Radiotherapy (IMRT) and complex treatment modalities such as stereotactic radiosurgery and helical tomotherapy were started to be implemented. Thus, due to increased local control of tumor growth and reduction of dose received by surrounding critical organs, serious complications were avoided. In this new treatment modality, while calculating appropriate dose, all the parameters such as patient anatomy and characteristics of radiation should be taken into account. Besides, during conformal radiotherapy, if hip prosthesis is located around or in the clinical target volume (CTV), type, thickness and density of biomaterial should be considered to avoid dose differences.     

Dosimetric comparison of MRI-based HDR brachytherapy and stereotactic radiotherapy in patients with advanced cervical cancer: A virtual brachytherapy study

AimTo evaluate the treatment plans of 3D image-guided brachytherapy (BT) and stereotactic robotic radiotherapy with online image guidance – CyberKnife (CK) in patients with locally advanced cervix cancer.Methods and materialsTen pairs of plans for patients with locally advanced inoperable cervical cancer were created using MR based 3D brachytherapy and stereotaxis CK. The dose that covers 98% of the target volume (HR CTV D98) was taken as a reference and other parameters were compared.ResultsOf the ten studied cases, the dose from D100 GTV was comparable for both devices, on average, the BT GTV D90 was 10–20% higher than for CK. The HR CTV D90 was higher for CK with an average difference of 10–20%, but only fifteen percent of HR CTV (the peripheral part) received a higher dose from CK, while 85% of the target volume received higher doses from BT. We found a significant organ-sparing effect of CK compared to brachytherapy (20–30% lower doses in 0.1 cm³, 1 cm³, and 2 cm³).ConclusionBT remains to be the best method for dose escalation. Due to the significant organ-sparing effect of CK, patients that are not candidates for BT could benefit from stereotaxis more than from classical external beam radiotherapy.