Real-time, ray casting-based scatter dose estimation for c-arm x-ray system.

OBJECTIVES: Dosimetric control of staff exposure during interventional procedures under fluoroscopy is of high relevance. In this paper, a novel ray casting approximation of radiation transport is presented and the potential and limitation vs. a full Monte Carlo transport and dose measurements are discussed. METHOD: The x-ray source of a Siemens Axiom Artix C-arm is modeled by a virtual source model using single Gaussian-shaped source. A Geant4-based Monte Carlo simulation determines the radiation transport from the source to compute scatter from the patient, the table, the ceiling and the floor. A phase space around these scatterers stores all photon information. Only those photons are traced that hit a surface of phantom that represents medical staff in the treatment room, no indirect scattering is considered; and a complete dose deposition on the surface is calculated. To evaluate the accuracy of the approximation, both experimental measurements using Thermoluminescent dosimeters (TLDs) and a Geant4-based Monte Carlo simulation of dose depositing for different tube angulations of the C-arm from cranial-caudal angle 0° and from LAO (Left Anterior Oblique) 0°-90° are realized. Since the measurements were performed on both sides of the table, using the symmetry of the setup, RAO (Right Anterior Oblique) measurements were not necessary. RESULTS: The Geant4-Monte Carlo simulation agreed within 3% with the measured data, which is within the accuracy of measurement and simulation. The ray casting approximation has been compared to TLD measurements and the achieved percentage difference was -7% for data from tube angulations 45°-90° and -29% from tube angulations 0°-45° on the side of the x-ray source, whereas on the opposite side of the x-ray source, the difference was -83.8% and -75%, respectively. Ray casting approximation for only LAO 90° was compared to a Monte Carlo simulation, where the percentage differences were between 0.5-3% on the side of the x-ray source where the highest dose usually detected was mainly from primary scattering (photons), whereas percentage differences between 2.8-20% are found on the side opposite to the x-ray source, where the lowest doses were detected. Dose calculation time of our approach was 0.85 seconds. CONCLUSION: The proposed approach yields a fast scatter dose estimation where we could run the Monte Carlo simulation only once for each x-ray tube angulation to get the Phase Space Files (PSF) for being used later by our ray casting approach to calculate the dose from only photons which will hit an movable elliptical cylinder shaped phantom and getting an output file for the positions of those hits to be used for visualizing the scatter dose propagation on the phantom surface. With dose calculation times of less than one second, we are saving much time compared to using a Monte Carlo simulation instead. With our approach, larger deviations occur only in regions with very low doses, whereas it provides a high precision in high-dose regions.

DEGRO/DGK guideline for radiotherapy in patients with cardiac implantable electronic devices.

An increasing number of patients undergoing radiotherapy (RT) have cardiac implantable electronic devices [CIEDs, cardiac pacemakers (PMs) and implanted cardioverters/defibrillators (ICDs)]. Ionizing radiation can cause latent and permanent damage to CIEDs, which may result in loss of function in patients with asystole or ventricular fibrillation. Reviewing the current literature, the interdisciplinary German guideline (DEGRO/DGK) was developed reflecting patient risk according to type of CIED, cardiac condition, and estimated radiation dose to the CIED. Planning for RT should consider the CIED specifications as well as patient-related characteristics (pacing-dependent, previous ventricular tachycardia/fibrillation). Antitachyarrhythmia therapy should be suspended in patients with ICDs, who should be under electrocardiographic monitoring with an external defibrillator on stand-by. The beam energy should be limited to 6 (to 10) MV CIEDs should never be located in the beam, and the cumulative scatter radiation dose should be limited to 2 Gy. Personnel must be able to respond adequately in the case of a cardiac emergency and initiate basic life support, while an emergency team capable of advanced life support should be available within 5 min. CIEDs need to be interrogated 1, 3, and 6 months after the last RT due to the risk of latent damage.

A novel end-to-end test for combined dosimetric and geometric treatment verification using a 3D-printed phantom.

The dosimetric and geometric accuracy are important components to ensure safe patient treatment in radiation therapy. Therefore, these components must be checked during quality control. This work presents a possible solution for the determination of the geometric isocenter deviation in the entire treatment chain. Additionally, the dose measurement of the established end-to-end test workflow measured in the same procedure as the geometric deviation is described. An in-house designed end-to-end test phantom went through the entire procedure of a standard patient treatment and the dosimetric and geometric accuracy were determined. At 3 linear accelerators (linac), the phantom was positioned either with cone beam computed tomography or with surface guidance. In this position, a Winston-Lutz test was performed and the deviations of the gantry, collimator and couch isocenter measurements to the phantom position were determined. Additionally, a dose measurement in the phantom was performed and compared to the dose predicted in the treatment planning system. To validate the results obtained with the in-house designed phantom, comparative measurements with commercial phantoms were performed. According to the performed end-to-end test, 2 out of the 3 linacs showed isocenter variations larger than 1 mm for collimator and gantry rotations and larger than 2 mm for couch rotations. With an isocenter variation of less than 1 mm for collimator and gantry rotations, 1 linac fulfilled the tolerance for stereotactic treatments without couch rotation. With couch rotation, an isocenter variation of less than 2 mm was detected at this linac, which fulfilled the tolerance for IMRT treatments. The mean dose deviation between measurement and treatment planning system was 1.82% ± 1.03%. The results acquired with the UMM phantom did not show statistically significant deviations to those acquired with relevant other commercial phantoms. The novel end-to-end test procedure allows for a combined dosimetric and geometric treatment evaluation. Besides the commonly performed dose end-to-end test the geometric isocenter deviation within a patient treatment workflow was evaluated and categorized for IMRT or SBRT.

Dosimetric benefits of daily treatment plan adaptation for prostate cancer stereotactic body radiotherapy.

BACKGROUND: Hypofractionation is increasingly being applied in radiotherapy for prostate cancer, requiring higher accuracy of daily treatment deliveries than in conventional image-guided radiotherapy (IGRT). Different adaptive radiotherapy (ART) strategies were evaluated with regard to dosimetric benefits. METHODS: Treatments plans for 32 patients were retrospectively generated and analyzed according to the PACE-C trial treatment scheme (40 Gy in 5 fractions). Using a previously trained cycle-generative adversarial network algorithm, synthetic CT (sCT) were generated out of five daily cone-beam CT. Dose calculation on sCT was performed for four different adaptation approaches: IGRT without adaptation, adaptation via segment aperture morphing (SAM) and segment weight optimization (ART1) or additional shape optimization (ART2) as well as a full re-optimization (ART3). Dose distributions were evaluated regarding dose-volume parameters and a penalty score. RESULTS: Compared to the IGRT approach, the ART1, ART2 and ART3 approaches substantially reduced the V37Gy(bladder) and V36Gy(rectum) from a mean of 7.4cm3 and 2.0cm3 to (5.9cm3, 6.1cm3, 5.2cm3) as well as to (1.4cm3, 1.4cm3, 1.0cm3), respectively. Plan adaptation required on average 2.6 min for the ART1 approach and yielded doses to the rectum being insignificantly different from the ART2 approach. Based on an accumulation over the total patient collective, a penalty score revealed dosimetric violations reduced by 79.2%, 75.7% and 93.2% through adaptation. CONCLUSION: Treatment plan adaptation was demonstrated to adequately restore relevant dose criteria on a daily basis. While for SAM adaptation approaches dosimetric benefits were realized through ensuring sufficient target coverage, a full re-optimization mainly improved OAR sparing which helps to guide the decision of when to apply which adaptation strategy.

Clinical implementation of volumetric intensity-modulated arc therapy (VMAT) with ERGO++.

BACKGROUND AND PURPOSE: Volumetric modulated arc therapy (VMAT) has the potential to deliver dose distributions comparable to the established intensity-modulated radiotherapy techniques for a multitude of target paradigms. Prior to implementing VMAT into their clinical routine in December 2008, the authors evaluated the dose calculation/delivery accuracy of 24 sample VMAT plans (prostate and anal cancer target paradigms) with film and ionization dosimetry. After the start of the clinical program, in vivo measurements with a rectal probe were performed. MATERIAL AND METHODS: The VMAT plans were generated by the treatment-planning system (TPS) ERGO++ (Elekta, Crawley, UK) and transferred to a phantom. Film dosimetry was performed with Kodak EDR2 films, and evaluated with dose profiles and gamma-index analysis. Appropriate ionization chambers were used for absolute dose measurements in the phantom and for in vivo measurements. The ionization chamber was used with localization of the measurement volume based on positioning cone-beam computed tomography. RESULTS: Plans were transferred from ERGO++ to the record and verify (R&V) system/linear accelerator (linac). The absolute dose deviations recorded with the ionization chamber were 1.74% +/- 1.62% across both indications. The gamma-index analysis of the film dosimetry showed no deviation > 3%/3 mm in the high-dose region. On in vivo measurements, a deviation between calculation and measurement of 2.09% +/- 2.4% was recorded, when the chamber was successfully positioned in the high-dose region. CONCLUSION: VMAT plans can be planned and treated reproducibly in high quality after the commissioning of the complete delivery chain consisting of TPS, R&V system and linac. The results of the individual plan verification meet the commonly accepted requirements. The first in vivo measurements confirm the reproducible precision of the delivered dose during clinical treatments.

Evaluation of a cycle-generative adversarial network-based cone-beam CT to synthetic CT conversion algorithm for adaptive radiation therapy.

PURPOSE: Image-guided radiation therapy could benefit from implementing adaptive radiation therapy (ART) techniques. A cycle-generative adversarial network (cycle-GAN)-based cone-beam computed tomography (CBCT)-to-synthetic CT (sCT) conversion algorithm was evaluated regarding image quality, image segmentation and dosimetric accuracy for head and neck (H&N), thoracic and pelvic body regions. METHODS: Using a cycle-GAN, three body site-specific models were priorly trained with independent paired CT and CBCT datasets of a kV imaging system (XVI, Elekta). sCT were generated based on first-fraction CBCT for 15 patients of each body region. Mean errors (ME) and mean absolute errors (MAE) were analyzed for the sCT. On the sCT, manually delineated structures were compared to deformed structures from the planning CT (pCT) and evaluated with standard segmentation metrics. Treatment plans were recalculated on sCT. A comparison of clinically relevant dose-volume parameters (D98, D50 and D2 of the target volume) and 3D-gamma (3%/3mm) analysis were performed. RESULTS: The mean ME and MAE were 1.4, 29.6, 5.4 Hounsfield units (HU) and 77.2, 94.2, 41.8 HU for H&N, thoracic and pelvic region, respectively. Dice similarity coefficients varied between 66.7 ± 8.3% (seminal vesicles) and 94.9 ± 2.0% (lungs). Maximum mean surface distances were 6.3 mm (heart), followed by 3.5 mm (brainstem). The mean dosimetric differences of the target volumes did not exceed 1.7%. Mean 3D gamma pass rates greater than 97.8% were achieved in all cases. CONCLUSIONS: The presented method generates sCT images with a quality close to pCT and yielded clinically acceptable dosimetric deviations. Thus, an important prerequisite towards clinical implementation of CBCT-based ART is fulfilled.

Ultrafast high-resolution in vivo volume-CTA of mice cerebral vessels.

BACKGROUND AND PURPOSE: Animal models developed in rats and mice have become indispensable in preclinical cerebrovascular research. Points of interest include the investigation of the vascular bed and the morphology and function of the arterial, capillary, and venous vessels. Because of their extremely small caliber, in vivo examination of these vessels is extremely difficult. In the present study we have developed a method to provide fast 3D in vivo analysis of cerebral murine vessels using volume computed tomography-angiography (vCTA). METHODS: Using an industrial X-ray inspection system equipped with a multifocus cone beam X-ray source and a 12-bit direct digital flatbed detector, high-speed vCTA (180 degrees rotation in 40 s. at 30 fps) was performed in anesthetized mice. During the scan an iodinated contrast agent was infused via a tail vein. Images were reconstructed using a filtered backprojection algorithm. Image analysis was performed by maximum intensity projection (MIP) and 3D volume reconstruction. RESULTS: All mice tolerated i.v. injection of the iodinated contrast agent well. Smallest achievable voxel size of raw data while scanning the whole neurocranium was 16 mum. Anatomy of cerebral vessels was assessable in all animals, and anatomic differences between mouse strains could easily be detected. Mean vessel diameter was measured in C57BL/6 and BALBc mice. Changes of vessel caliber were assessable by repeated vCTA. CONCLUSIONS: Ultra fast in vivo vCTA of murine cerebral vasculature is feasible at resolutions down to 16 mum. The technique allows the assessment of vessel caliber changes in living mice, thus providing an interesting tool to monitor different features such as vasospasm or vessel patency.

[Patient-centered image and data management in radiation oncology]. / Patientenbezogenes Bild- und Datenmanagement in der Radioonkologie.

BACKGROUND: : Recent changes in the radiotherapy (RT) workflow through the introduction of complex treatment paradigms such as intensity-modulated radiotherapy (IMRT) and, recently, image-guided radiotherapy (IGRT) with their increase in data traffic for different data classes have mandated efforts to further integrate electronic data management for RT departments in a patient- and treatment-course-centered fashion. METHODS: : Workflow in an RT department is multidimensional and multidirectional and consists of at least five different data classes (RT/machine data, patient-related documents such as reports and letters, progress notes, DICOM [Digital Imaging and Communications in Medicine] image data, and non-DICOM image data). Data has to be handled in the framework of adaptive feedback loops with increasing frequency. This is in contrast to a radiology department where mainly DICOM image data and reports have to be widely accessible but are dealt with in a mainly unidirectional manner. When compared to a diagnostic Radiology Information System (RIS)/Picture Archiving and Communication System (PACS), additional legal requirements have to be conformed to when an integrated electronic RT data management system is installed. Among these are extended storage periods, documentation of treatment plan approval by physicians and physicist, documentation of informed consent, etc. CONCLUSION: : Since the transition to a paper- and filmless environment in medicine and especially in radiation oncology is unavoidable, this review discusses these issues and suggests a possible hardware and organizational architecture of an RT department information system under control of a Hospital Information System (HIS), based on combined features of genuine RT Record and Verify (R&V) Systems, PACS, and Electronic Medical Records (EMR).

Optimization of the gafchromic EBT protocol for IMRT QA.

Quality assurance of external beam (radio)therapy (EBT) requires tools with specific characteristics. A radiochromic film dubbed "Gafchromic EBT" (G-EBT) that is particularly suited for external beam therapy because of its features was introduced in 2004. Its characteristics, especially the high spatial resolution, make it suitable for measurement of dose distributions in radiotherapy, especially intensity-modulated radiation therapy (IMRT). While several aspects of the film characteristics have been previously reported separately, we present a comprehensive evaluation centered on practical IMRT verification, leading to an optimized protocol. Therefore the constancy within one batch, the relationship between optical density (OD) and dose (dose range between 1.4 Gy and 8.4 Gy) and the dose rate dependence for four dose rates (55, 108, 217, 441 MU/min) were investigated. In addition to these characteristics, energy dependence between two energies (50kV and 6 MV), tissue equivalency, post irradiation coloration over one month, pressure and temperature sensitivity were evaluated. We then optimized the protocol using the G-EBT films, in combination with an EPSON-Expression 1680 pro flatbed scanner, for IMRT QA, while either striving to keep the compound error as small as possible or trying to reduce evaluation time. As a basis for this protocol optimization, the characteristics of the scanner (such as inhomogeneity of the scanning field) and its software (such as consequences of extracting only the red color channel) had to be determined first. The interaction of film and scanner (variation of the OD depending on the scanning direction or the scanning resolution) was assessed as well. Using the optimized protocol for IMRT QA, the compound error could be reduced to approximately 2% for a quality-driven approach and maximum 5.5% for an approach attempting to reduce procedure time. While the quality-driven approach provides appropriate accuracy for individual patient QA, the procedure-time driven approach can only be used for preliminary measurements.

Ultrafast single breath-hold cone-beam CT lung cancer imaging with faster linac gantry rotation.

PURPOSE: Lung tumors treated with hypo-fractionated deep-inspiration breath-hold stereotactic body radiotherapy benefit from fast imaging and treatment. Single breath-hold cone-beam-CT (CBCT) could reduce motion artifacts and improve treatment precision. Thus, gantry speed was accelerated to 18°/s, limiting acquisition time to 10-20 s. Image quality, dosimetry and registration accuracy were compared with standard-CBCT (3°/s). METHODS AND MATERIALS: For proof-of-concept, image quality was analyzed following customer acceptance tests, CT-dose index measured, and registration accuracy determined with an off-centered ball-bearing-phantom. A lung-tumor patient was simulated with differently shaped tumor-mimicking inlays in a thorax-phantom. Signal-to-noise-ratio, contrast-to-noise-ratio and geometry of the inlays quantified image quality. Dose was measured in representative positions. Registration accuracy was determined with inlays scanned in pre-defined positions. Manual, automatic (clinical software) and objective-automatic (in-house-developed) registration was performed on planning-CT, offsets between results and applied shifts were compared. RESULTS: Image quality of ultrafast-CBCT was adequate for high-contrast areas, despite contrast-reduction of ∼80% due to undersampling. Dose-output was considerably reduced by 60-83% in presented setup; variations are due to gantry-braking characteristics. Registration accuracy was maintained better than 1 mm, mean displacement errors were 0.0 ±â€¯0.2 mm with objective-automatic registration. Ultrafast-CBCT showed no significant registration differences to standard-CBCT. CONCLUSIONS: This study of first tests with faster gantry rotation of 18°/s showed promising results for ultrafast high-contrast lung tumor CBCT imaging within single breath-hold of 10-20 s. Such fast imaging times, in combination with fast treatment delivery, could pave the way for intra-fractional combined imaging and treatment within one breath-hold phase, and thus mitigate residual motion and increase treatment accuracy and patient comfort. Even generally speaking, faster gantry rotation could set a benchmark with immense clinical impact where time matters most: palliative patient care, general reduction in uncertainty, and increase in patient throughput especially important for emerging markets with high patient numbers.

Radiation-induced optic neuropathy after stereotactic and image guided intensity-modulated radiation therapy (IMRT).

BACKGROUND/PURPOSE: To quantify the risk of radiation-induced optic neuropathy (RION) after stereotactic/image-guided positioning and intensity-modulated radiotherapy (IMRT) with ≥50 Gy to the anterior visual pathway (AVP). METHODS: Patients irradiated with ≥50 Gy to the AVP using stereotactic/image-guided positioning between 2002 and 2011 in Mannheim were identified. Detailed dosimetric data were collected and patients or family members were retrospectively asked to rate visual acuity and visual disorders. RESULTS: 125 patients fulfilled the eligibility criteria. Average maximum equivalent point dose (Dmax-EQD-2[α/ß=1.6]) to the AVP was 53.1 ±â€¯3.9 Gy. 99 patients received ≥50 Gy bilaterally (chiasm or both optic nerves), resulting in 224 (99x2 bilateral plus 26 unilateral) visual-fields-at-risk (VFAR) for RION. Eighty-two patients provided pre/post-IMRT visual status information (n = 151 VFARs). Permanent visual deterioration occurred in 18 (22%) patients. In seven, visual deterioration was possibly related to radiotherapy (two-sided deterioration in one patient) for a crude incidence of 8.5% (7/82 patients) and 5.3% (8/151 VFARs). Two cases were caused by chronic keratitis/conjunctivitis; in five patients RION could not be excluded (one two-sided). In one of 13 patients with Dmax-EQD-2 > 58 Gy, RION could not be excluded. In all affected patients, visual acuity post-IMRT had decreased only mildly (1-2 points on the 5-point-scale). One patient with relevant baseline visual impairment (3/5) developed unilateral blindness (crude incidence of blindness on patient-/VFAR-level: 1.2% and 0.66%; competing risk-adjusted/actuarial 24-month incidence: patient/VFAR-level: 1.8% and 0.95%). CONCLUSION: Risk of RION was low in this cohort with accurate positioning and precise dosimetric information. Less conservative tolerance doses may be considered in patients with high risk of recurrence.

Fully automated, multi-criterial planning for Volumetric Modulated Arc Therapy - An international multi-center validation for prostate cancer.

BACKGROUND AND PURPOSE: Reported plan quality improvements with autoplanning of radiotherapy of the prostate and seminal vesicles are poor. A system for automated multi-criterial planning has been validated for this treatment in a large international multi-center study. The system is configured with training plans using a mechanism that strives for quality improvements relative to those plans. MATERIAL AND METHODS: Each of the four participating centers included thirty manually generated clinical Volumetric Modulated Arc Therapy prostate plans (manVMAT). Ten plans were used for autoplanning training. The other twenty were compared with an automatically generated plan (autoVMAT). Plan evaluations considered dosimetric plan parameters and blinded side-by-side plan comparisons by clinicians. RESULTS: With equivalent Planning Target Volume (PTV) V95%, D2%, D98%, and dose homogeneity autoVMAT was overall superior for rectum with median differences of 3.4 Gy (p < 0.001) in Dmean, 4.0% (p < 0.001) in V60Gy, and 1.5% (p = 0.001) in V75Gy, and for bladder Dmean (0.9 Gy, p < 0.001). Also the clinicians' plan comparisons pointed at an overall preference for autoVMAT. Advantages of autoVMAT were highly treatment center- and patient-specific with overall ranges for differences in rectum Dmean and V60Gy of [-4,12] Gy and [-2,15]%, respectively. CONCLUSION: Observed advantages of autoplanning were clinically relevant and larger than reported in the literature. The latter is likely related to the multi-criterial nature of the applied autoplanning algorithm, with for each center a dedicated configuration that aims at plan improvements relative to its (clinical) training plans. Large variations among patients in differences between manVMAT and autoVMAT point at inconsistencies in manual planning.

Intraoperative radiotherapy (IORT) is an option for patients with localized breast recurrences after previous external-beam radiotherapy.

BACKGROUND: For patients suffering of recurrent breast cancer within the irradiated breast, generally mastectomy is recommended. The normal tissue tolerance does not permit a second full-dose course of radiotherapy to the entire breast after a second breast-conserving surgery (BCS). A novel option is to treat these patients with partial breast irradiation (PBI). This approach is based on the hypothesis that re-irradiation of a limited volume will be effective and result in an acceptable frequency of side effects. The following report presents a single center experience with intraoperative radiotherapy (IORT) during excision of recurrent breast cancer in the previously irradiated breast. METHODS: Between 4/02 and 11/06, 15 patients were treated for in-breast recurrences at a median of 10 years (3-25) after previous EBRT (10 recurrences in the initial tumor bed, 3 elsewhere in-breast failures, 2 invasive recurrences after previous DCIS). Additional 2 patients were selected for IORT with new primary breast cancer after previous partial breast EBRT for treatment of Hodgkin's disease. IORT with a single dose of 14.7 - 20 Gy 50 kV X-rays at the applicator surface was delivered with the Intrabeam-device (Carl Zeiss, Oberkochen, Germany). RESULTS: After a median follow-up of 26 months (1-60), no local recurrence occurred. 14 out of 17 patients are alive and free of disease progression. Two patients are alive with distant metastases. One patient died 26 months after BCS/IORT due to pulmonary metastases diagnosed 19 months after BCS/IORT. Acute toxicity after IORT was mild with no Grade 3/4 toxicities and cosmetic outcome showed excellent/good/fair results in 7/7/3 cases. CONCLUSION: IORT for recurrent breast cancer using low energy X-rays is a valuable option for patients with recurrent breast cancer after previous radiotherapy.

Long-term toxicity of an intraoperative radiotherapy boost using low energy X-rays during breast-conserving surgery.

PURPOSE: Intraoperative radiotherapy (IORT) as a boost for breast cancer delivers a high single dose of radiation to a late-reacting tissue; therefore late toxicity is of particular interest, and long-term follow-up is warranted. To date there are only limited data available on breast cancer patients treated with IORT using low energy X-rays. We analyzed toxicity and cosmesis after IORT as a boost with a minimum follow-up of 18 months. METHODS AND MATERIALS: A total of 73 patients treated with IORT (20 Gy/50 kV X-rays; INTRABEAM [Carl Zeiss Surgical, Oberkochen, Germany]) to the tumor bed during breast-conserving surgery as a boost followed by whole-breast radiotherapy (WBRT, 46 Gy) underwent a prospective, predefined follow-up (median, 25 months; range 18-44 months), including clinical examination and breast ultrasound at 6-months and mammographies at 1-year intervals. Toxicities were documented using the common toxicity criteria (CTC)/European Organization for Research and Treatment of Cancer and the LENT-SOMA score. Cosmesis was evaluated with a score from 1 to 4. RESULTS: The IORT in combination with WBRT was well tolerated, with no Grade 3 or 4 skin toxicities and no telangiectasias. Fibrosis of the entire breast was observed in 5% of the patients. A circumscribed fibrosis around the tumor bed was palpable in up to 27% with a peak around 18 months after therapy and a decline thereafter. The observed toxicitiy rates were not influenced by age, tumor stage, or systemic therapy. The cosmetic outcome was good to excellent in>or=90% of cases. CONCLUSIONS: After IORT of the breast using low-energy X-rays, no unexpected toxicity rates were observed during long-term-follow-up.

Radiobiological aspects of intraoperative radiotherapy (IORT) with isotropic low-energy X rays for early-stage breast cancer.

The purpose of this study was to model the distribution of biological effect around a miniature isotropic X-ray source incorporating spherical applicators for single-dose or hypo-fractionated partial-breast intraoperative radiotherapy. A modification of the linear-quadratic formalism was used to calculate the relative biological effectiveness (RBE) of 50 kV X rays as a function of dose and irradiation time for late-reacting normal tissue and tumor cells. The response was modeled as a function of distance in the tissue based on the distribution of equivalent dose and published dose-response data for pneumonitis and subcutaneous fibrosis after single-dose conventional irradiation. Furthermore, the spatial distribution of tumor cell inactivation was assessed. The RBE for late reactions approached unity at the applicator surface but increased as the absorbed dose decreased with increasing distance from the applicator surface. The ED50 for pneumonitis was estimated to be reached at a depth of 6-11 mm in the tissue and that for subcutaneous fibrosis at 3-6 mm, depending on the applicator diameter and whether the effect of recovery was included. Thus lung tissue would be spared because of the thickness of the thorax wall. The RBE for tumor cells was higher than for late-reacting tissue. The applicator diameter is an important parameter in determining the range of tumor cell control in the irradiated tumor bed.

Intraoperative radiotherapy (IORT) for breast cancer using the Intrabeam system.

INTRODUCTION: Intraoperative radiotherapy (IORT) with low-energy X-rays (30-50 KV) is an innovative technique that can be used both for accelerated partial breast irradiation (APBI) and intraoperative boosting in patients affected by breast cancer. Immediately after tumor resection the tumor bed can be treated with low-distance X-rays by a single high dose. Whereas often a geographic miss in covering the boost target occurs with external beam boost radiotherapy (EBRT), the purpose of IORT is to cover the tumor bed safely. This report will focus on the feasibility and technical aspects of the Intrabeam device and will summarize our experience with side effects and local control. MATERIALS AND METHODS: Between February 2002 and June 2003 57 breast cancer patients, all eligible for breast conserving surgery (BCS), were treated at the Mannheim Medical Center with IORT using the mobile X-ray system Intrabeam. The patient population in this feasibility study was not homogeneous consisting of 49 patients with primary stage I or II breast cancer, seven with local recurrence after previous EBRT and one with a second primary in a previously irradiated breast. The selection criteria for referral for IORT included tumor size, tumor cavity size, margin status and absence of an extensive intraductal component. The previously irradiated patients with local recurrences and 16 others received IORT as single modality. In all other cases IORT was followed by EBRT with a total dose of 46 Gy in 2-Gy fractions. The intraoperatively delivered dose after tumor resection was 20 Gy prescribed to the applicator surface. EBRT was delivered with a standard two-tangential-field technique using linear accelerators with 6- or 18-MV photons. Patients were assessed every three months by their radiation oncologist or surgeon during the first year after treatment and every six months thereafter. Breast ultrasound for follow-up was done every six months and mammographies once yearly. Acute side effects were scored according to the CTC/EORTC score and late side effects according to the Lent-Soma classification. RESULTS: Twenty-four patients received IORT only; eight patients because they had received previous radiotherapy, 16 because of a very favorable risk profile or their own preference. Thirty-three patients with tumor sizes between 1 and 30 mm and no risk factors were treated by IORT as a boost followed by EBRT. The Intrabeam system was used for IORT. The Intrabeam source produces 30-50 KV X-rays and the prescribed dose is delivered in an isotropic dose distribution around spherical applicators. Treatment time ranged between 20 and 48 minutes. No severe acute side effects or complications were observed during the first postoperative days or after 12 months. One local recurrence occurred 10 months after surgery plus IORT followed by EBRT. In two patients distant metastases were diagnosed shortly after BCS. DISCUSSION: IORT with the Intrabeam system is a feasible method to deliver a single high radiation dose to breast cancer patients. As a preliminary boost it has the advantage of reducing the EBRT course by 1.5 weeks, and as APBI it might be a promising tool for patients with a low risk of recurrence. The treatment is well tolerated and does not cause greater damage than the expected late reaction in normal tissue.

IMRT for postoperative treatment of gastric cancer: covering large target volumes in the upper abdomen: a comparison of a step-and-shoot and an arc therapy approach.

PURPOSE: Data from the randomized Intergroup Trial 116 suggest effectiveness of adjuvant radiochemotherapy in patients with advanced gastric cancer. Late toxicity, however, especially with respect to the kidneys, may pose significant longtime problems. Intensity-modulated radiotherapy (IMRT) may reduce toxicity to organs at risk. To evaluate the relative merits of different IMRT approaches, we performed a plan comparison between a step-and-shoot class solution and an AP-PA setup, a conventional box technique and the Peacock tomotherapy approach. METHODS AND MATERIALS: Computed tomographies and structure data from 15 patients who had been treated postoperatively for advanced (T3/T4/N+) gastric cancer at our department formed the basis of our plan comparison study. For each patient data set, 5 plans or plan combinations (conventional 3D plan, AP-PA plan, step-and-shoot IMRT, tomotherapy with 1-cm or 2-cm collimation) were chosen, and evaluation was performed for a total dose of 45 Gy delivered as the median dose to the target volume for each plan or plan combination. RESULTS: Median kidney dose generated from the IMRT plans is reduced individually by >50% for the kidney with the highest exposure (usually the left kidney) from 20 to 30 Gy with conventional 3D planning down to values between 8 and 10 Gy for IMRT. On average, median dose to the right kidney is the same for the conventional box technique and IMRT (between 8 and 10 Gy) but lower for the AP-PA technique. In 3 patients, kidney dose might have been ablative for both kidneys with both the AP-PA technique and the box technique, whereas it was acceptable with IMRT. Median dose to the liver was subcritical with all modalities but lowest with AP-PA fields. Differences between step-and-shoot IMRT and tomotherapy plans are small when compared to the differences between IMRT plans and conventional conformal 3D plans. For some patients, however, their body and target diameters obviate treatment with tomotherapy. Treatment time for the step-and-shoot approach and for tomotherapy with 2-cm collimation can be kept <20 min. CONCLUSIONS: For postoperative radiotherapy of advanced gastric cancer, step-and-shoot IMRT as well as tomotherapy can deliver efficient doses to target volumes while delivering dose to the kidneys in a fashion that is different from a conventional technique and is clearly advantageous in a small number of patients. An advantage for the majority of patients is likely with the normal tissue complication probability data presented in this series, but, given the uncertainty of the reaction of the kidney to inhomogeneous dose distributions, cannot be considered unequivocal at the moment. Different technical limitations apply to the different IMRT techniques. The choice of approach is therefore determined by departmental circumstances.

Radiation protection for an intraoperative X-ray source compared to C-arm fluoroscopy.

BACKGROUND: Intraoperative radiotherapy (IORT) using the INTRABEAM(®) system promises a flexible use regarding radiation protection compared to other approaches such as electron treatment or HDR brachytherapy with (192)Ir or (60)Co. In this study we compared dose rate measurements of breast- and Kypho-IORT with C-arm fluoroscopy which is needed to estimate radiation protection areas. MATERIALS AND METHODS: C-arm fluoroscopy, breast- and Kypho-IORTs were performed using phantoms (silicon breast or bucket of water). Dose rates were measured at the phantom's surface, at 30 cm, 100 cm and 200 cm distance. Those measurements were confirmed during 10 Kypho-IORT and 10 breast-IORT patient treatments. RESULTS: The measured dose rates were in the same magnitude for all three paradigms and ranges from 20 µSv/h during a simulated breast-IORT at two meter distance up to 64 mSv/h directly at the surface of a simulated Kypho-IORT. Those measurements result in a circle of controlled area (yearly doses >6 mSv) for each paradigm of about 4 m±2 m. DISCUSSION/CONCLUSIONS: All three paradigms show comparable dose rates which implies that the radiation protection is straight forward and confirms the flexible use of the INTRABEAM(®) system.

Arc therapy for total body irradiation--a robust novel treatment technique for standard treatment rooms.

BACKGROUND AND PURPOSE: We developed a simple and robust total body irradiation (TBI) method for standard treatment rooms that obviates the need for patient translation devices. METHODS AND MATERIALS: Two generic arcs with rectangular segments for a patient thickness of 16 and 20 cm (arc16/arc20) were generated. An analytical fit was performed to determine the weights of the arc segments depending on patient thickness and gantry angle. Stability and absolute dose for both arcs were measured using EBT3 films in a range of solid water slab phantom thicknesses. Additionally ionization chamber measurements were performed every 10 cm at a source surface distance (SSD) of ∼ 200 cm. RESULTS: The measured standard deviation for arc16 is ± 3% with a flatness ⩽ 9.0%. Arc20 had a standard deviation of ± 3% with a flatness ⩽ 7.3% for all measured thicknesses. The theoretical curves proved to be accurate for the prediction of the segment weightings for the two arcs. In vivo measurements for the first 22 clinical patients showed a dose deviation of less than 3%. CONCLUSIONS: Arc therapy is a convenient and stable method for TBI. This cost-effective approach has been introduced clinically, obviating the need for field patches and to physically move the patient.

Second cancer risk after 3D-CRT, IMRT and VMAT for breast cancer.

PURPOSE: Second cancer risk after breast conserving therapy is becoming more important due to improved long term survival rates. In this study, we estimate the risks for developing a solid second cancer after radiotherapy of breast cancer using the concept of organ equivalent dose (OED). MATERIALS AND METHODS: Computer-tomography scans of 10 representative breast cancer patients were selected for this study. Three-dimensional conformal radiotherapy (3D-CRT), tangential intensity modulated radiotherapy (t-IMRT), multibeam intensity modulated radiotherapy (m-IMRT), and volumetric modulated arc therapy (VMAT) were planned to deliver a total dose of 50 Gy in 2 Gy fractions. Differential dose volume histograms (dDVHs) were created and the OEDs calculated. Second cancer risks of ipsilateral, contralateral lung and contralateral breast cancer were estimated using linear, linear-exponential and plateau models for second cancer risk. RESULTS: Compared to 3D-CRT, cumulative excess absolute risks (EAR) for t-IMRT, m-IMRT and VMAT were increased by 2 ± 15%, 131 ± 85%, 123 ± 66% for the linear-exponential risk model, 9 ± 22%, 82 ± 96%, 71 ± 82% for the linear and 3 ± 14%, 123 ± 78%, 113 ± 61% for the plateau model, respectively. CONCLUSION: Second cancer risk after 3D-CRT or t-IMRT is lower than for m-IMRT or VMAT by about 34% for the linear model and 50% for the linear-exponential and plateau models, respectively.