ArthroRad trial: randomized multicenter single-blinded trial on the effect of low-dose radiotherapy for painful osteoarthritis-final results after 12-month follow-up.

OBJECTIVE: Updated report about the randomized comparison of the effect of radiotherapy on painful osteoarthritis (OA) applying a standard dose vs. a very low dose regime after a follow-up of 1 year. PATIENTS AND METHODS: Patients presenting with OA of the hand/finger and knee joints were included. After randomization (every joint region was randomized separately) the following protocols were applied: (a) standard arm: total dose 3.0 Gy, single fractions of 0.5 Gy twice a week; (b) experimental arm: total dose 0.3 Gy, single fractions of 0.05 Gy twice a week. The dosage was blinded for the patients. For evaluation the scores after 1­year visual analog scale (VAS), Knee Injury and Osteoarthritis Outcome Score-Short Form (KOOS-PS), Short Form Score for the Assessment and Quantification of Chronic Rheumatic Affections of the Hands (SF-SACRAH) and 12-item Short-Form Health Survey (SF-12) were used (for further details: see [1]). RESULTS: The standard dose was applied to 77 hands and 33 knees, the experimental dose was given to 81 hands and 30 knees. After 12 months, the data of 128 hands and 45 knees were available for evaluation. Even after this long time, we observed a favorable response of pain to radiotherapy in both trial arms; however, there were no reasonable statistically significant differences between both arms concerning pain, functional, and quality of life scores. Side effects did not occur. The only prognostic factor was the pain level before radiotherapy. CONCLUSIONS: We found a favorable pain relief and a limited response in the functional and quality of life scores in both treatment arms. The possible effect of low doses such as 0.3 Gy on pain is widely unknown.

Imaging doses for different CBCT protocols on the Halcyon 3.0 linear accelerator - TLD measurements in an anthropomorphic phantom.

INTRODUCTION: Image guided radiotherapy allows for particularly conformal tumour irradiation through precise patient positioning. Becoming the standard for radiotherapy, this increases imaging doses to the patient. The Halcyon 3.0 linear accelerator (Varian Medical Systems, Palo Alto, CA) requires daily imaging due to its geometry. For this reason, the accelerator is equipped with on-line kV and MV imaging. However, daily CBCT images required for irradiation apply additional radiation, which increases the dose to normal tissue and therefore can affect the patient's secondary cancer risk. In this study, actual organ doses were measured for the kV system, and a comparison of normal tissue doses for all available kV CBCT protocols was presented to demonstrate differences in imaging doses across entities and protocols. In addition, effective dose and secondary cancer risk from imaging are evaluated. MATERIAL AND METHODS: Measurements were performed with thermoluminescent dosimeters in an anthropomorphic phantom positioned according to each entity (brain, head and neck, breast, lung, pelvis). CBCT images were obtained, using all available pre-set protocols without further adjustment of the parameters. Measured doses for each position and each protocol were then compared and secondary cancer risk of relevant and specifically radiosensitive organs was calculated. RESULTS: It was found that imaging doses for protocols such as Pelvis and Head could be reduced by up to half using the corresponding Fast and Low Dose modes, respectively. On the other hand, larger field sizes or the Large mode yielded higher doses than their initial protocols. Image Gently was found to spare normal tissue best, however it is not suitable for certain entities due to low image quality or insufficient projection data. DISCUSSION: By using appropriate kV-CBCT protocols, it is possible to reduce imaging doses to a significant extent and therefore spare healthy tissue. Combined with studies of image quality, the results of this study could lead to adjustments in workflow regarding the choice of protocols used in daily routine. This could prevent unnecessary radiation exposure and reduce secondary cancer risk.

Measuring out-of-field dose to the hippocampus in common radiotherapy indications.

BACKGROUND: The high susceptibility of the hippocampus region to radiation injury is likely the causal factor of neurocognitive dysfunctions after exposure to ionizing radiation. Repetitive exposures with even low doses have been shown to impact adult neurogenesis and induce neuroinflammation. We address the question whether the out-of-field doses during radiotherapy of common tumour entities may pose a risk for the neuronal stem cell compartment in the hippocampus. METHODS: The dose to the hippocampus was determined for a single fraction according to different treatment plans for the selected tumor entities: Point dose measurements were performed in an anthropomorphic Alderson phantom and the out-of-field dose to the hippocampus was measured using thermoluminescence dosimeters. RESULTS: For carcinomas in the head and neck region the dose exposure to the hippocampal region for a single fraction ranged from to 37.4 to 154.8 mGy. The hippocampal dose was clearly different for naso-, oro- and hypopharynx, with maximal values for nasopharynx carcinoma. In contrast, hippocampal dose levels for breast and prostate cancer ranged between 2.7 and 4.1 mGy, and therefore significantly exceeded the background irradiation level. CONCLUSION: The mean dose to hippocampus for treatment of carcinomas in the head and neck region is high enough to reduce neurocognitive functions. In addition, care must be taken regarding the out of field doses. The mean dose is mainly related to scattering effects, as is confirmed by the data from breast or prostate treatments, with a very different geometrical set-up but similar dosimetric results.

Comparison of Breast Cancer Radiotherapy Techniques Regarding Secondary Cancer Risk and Normal Tissue Complication Probability - Modelling and Measurements Using a 3D-Printed Phantom.

Background: Radiotherapy after breast-conserving therapy is a standard postoperative treatment of breast cancer, which can be carried out with a variety of irradiation techniques. The treatment planning must take into consideration detrimental effects on the neighbouring organs at risk-the lung, the heart, and the contralateral breast, which can include both short- and long-term effects represented by the normal tissue complication probability and secondary cancer risk. Patients and Methods: In this planning study, we investigate intensity-modulated (IMRT) and three-dimensional conformal (3D-CRT) radiotherapy techniques including sequential or simultaneously integrated boosts as well as interstitial multicatheter brachytherapy boost techniques of 38 patients with breast-conserving surgery retrospectively. We furthermore develop a 3D-printed breast phantom add-on to allow for catheter placement and to measure the out-of-field dose using thermoluminescent dosimeters placed inside an anthropomorphic phantom. Finally, we estimate normal tissue complication probabilities using the Lyman-Kutcher-Burman model and secondary cancer risks using the linear non-threshold model (out-of-field) and the model by Schneider et al. (in-field). Results: The results depend on the combination of primary whole-breast irradiation and boost technique. The normal tissue complication probabilities for various endpoints are of the following order: 1%-2% (symptomatic pneumonitis, ipsilateral lung), 2%-3% (symptomatic pneumonitis, whole lung), and 1%-2% (radiation pneumonitis grade ≥ 2, whole lung). The additional relative risk of ischemic heart disease ranges from +25% to +35%. In-field secondary cancer risk of the ipsilateral lung in left-sided treatment is around 50 per 10,000 person-years for 20 years after exposure at age 55. Out-of-field estimation of secondary cancer risk results in approximately 5 per 10,000 person-years each for the contralateral lung and breast. Conclusions: In general, 3D-CRT shows the best risk reduction in contrast to IMRT. Regarding the boost concepts, brachytherapy is the most effective method in order to minimise normal tissue complication probability and secondary cancer risk compared to teletherapy boost concepts. Hence, the 3D-CRT technique in combination with an interstitial multicatheter brachytherapy boost is most suitable in terms of risk avoidance for treating breast cancer with techniques including boost concepts.

ArthroRad trial: multicentric prospective and randomized single-blinded trial on the effect of low-dose radiotherapy for painful osteoarthritis depending on the dose-results after 3 months' follow-up.

PURPOSE: Randomized comparison of the effect of radiotherapy on painful osteoarthritis (OA) applying a standard-dose vs. a very-low-dose regime PATIENTS AND METHODS: Patients with OA of the hand and knee joints were included. Further inclusion criteria: symptoms for more than 3 months, favorable general health status, age above 40 years. Patients with prior local radiotherapy, trauma, rheumatoid arthritis, or vascular diseases were excluded. After randomization (every joint was randomized separately), the following protocols were applied: standard arm: total dose 3.0 Gy, single fractions of 0.5 Gy twice weekly; experimental arm: total dose 0.3 Gy, single fractions of 0.05 Gy twice weekly. The dosage was not known to the patients. The patients were examined 3 and 12 months after radiotherapy. Scores like VAS (visual analogue scale), KOOS-SF (the knee injugy and osteoarthritis outcome score), SF-SACRAH (short form score for the assessment and quantification of chronic rheumatic affections of the hands), and SF-12 (short form 12) were used. RESULTS: A total of 64 knees and 172 hands were randomized. 3.0 Gy was applied to 87 hands and 34 knees, 0.3 Gy was given to 85 hands and 30 knees. After 3 months, we observed good pain relief after 3 Gy and after 0.3 Gy, there was no statistically significant difference. Side effects were not recorded. The trial was closed prematurely due to slow recruitment. CONCLUSION: We found favorable pain relief and a limited response in the functional and quality of life scores in both arms. The effect of low doses such as 0.3 Gy on pain is widely unknown. Further trials are necessary to compare a conventional dose to placebo and to further explore the effect of low doses on inflammatory disorders.

Feasibility and clinical usefulness of modelling glioblastoma migration in adjuvant radiotherapy.

Glioblastoma (GBM) is one of the most common primary brain tumours in adults, with a dismal prognosis despite aggressive multimodality treatment by a combination of surgery and adjuvant radiochemotherapy. A detailed knowledge of the spreading of glioma cells in the brain might allow for more targeted escalated radiotherapy, aiming to reduce locoregional relapse. Recent years have seen the development of a large variety of mathematical modelling approaches to predict glioma migration. The aim of this study is hence to evaluate the clinical applicability of a detailed micro- and meso-scale mathematical model in radiotherapy. First and foremost, a clinical workflow is established, in which the tumour is automatically segmented as input data and then followed in time mathematically based on the diffusion tensor imaging data. The influence of several free model parameters is individually evaluated, then the full model is retrospectively validated for a collective of 3 GBM patients treated at our institution by varying the most important model parameters to achieve optimum agreement with the tumour development during follow-up. Agreement of the model predictions with the real tumour growth as defined by manual contouring based on the follow-up MRI images is analyzed using the dice coefficient. The tumour evolution over 103-212 days follow-up could be predicted by the model with a dice coefficient better than 60% for all three patients. In all cases, the final tumour volume was overestimated by the model by a factor between 1.05 and 1.47. To evaluate the quality of the agreement between the model predictions and the ground truth, we must keep in mind that our gold standard relies on a single observer's (CB) manually-delineated tumour contours. We therefore decided to add a short validation of the stability and reliability of these contours by an inter-observer analysis including three other experienced radiation oncologists from our department. In total, a dice coefficient between 63% and 89% is achieved between the four different observers. Compared with this value, the model predictions (62-66%) perform reasonably well, given the fact that these tumour volumes were created based on the pre-operative segmentation and DTI.

Optimizing Adjuvant Stereotactic Radiotherapy of Motor-Eloquent Brain Metastases: Sparing the nTMS-Defined Motor Cortex and the Hippocampus.

Brain metastases can effectively be treated with surgical resection and adjuvant stereotactic radiotherapy (SRT). Navigated transcranial magnetic stimulation (nTMS) has been used to non-invasively map the motor cortex prior to surgery of motor eloquent brain lesions. To date, few studies have reported the integration of such motor maps into radiotherapy planning. The hippocampus has been identified as an additional critical structure of radiation-induced deficits. The aim of this study is to assess the feasibility of selective dose reduction to both the nTMS-based motor cortex and the hippocampi in SRT of motor-eloquent brain metastases. Patients with motor-eloquent brain metastases undergoing surgical resection and adjuvant SRT between 07/2014 and 12/2018 were retrospectively analyzed. The radiotherapy treatment plans were retrieved from the treatment planning system ("original" plan). For each case, two intensity-modulated treatment plans were created: the "motor" plan aimed to reduce the dose to the motor cortex, the "motor & hipp" plan additionally reduce the dose to the hippocampus. The optimized plans were compared with the "original" plan regarding plan quality, planning target volume (PTV) coverage, and sparing of organs at risk (OAR). 69 plans were analyzed, all of which were clinically acceptable with no significant differences for PTV coverage. All OAR were protected according to standard protocols. Sparing of the nTMS motor map was feasible: mean dose 9.66 ± 5.97 Gy (original) to 6.32 ± 3.60 Gy (motor) and 6.49 ± 3.78 Gy (motor & hipp), p<0.001. In the "motor & hipp" plan, dose to the ipsilateral hippocampi could be significantly reduced (max 1.78 ± 1.44 Gy vs 2.49 ± 1.87 Gy in "original", p = 0.003; mean 1.01 ± 0.92 Gy vs. 1.32 ± 1.07 Gy in "original", p = 0.007). The study confirms the results from previous studies that inclusion of nTMS motor information into radiotherapy treatment planning is possible with a relatively straightforward workflow and can achieve reduced doses to the nTMS-defined motor area without compromising PTV coverage. Furthermore, we demonstrate the feasibility of selective dose reduction to the hippocampus at the same time. The clinical significance of these optimized plans yet remains to be determined. However, with no apparent disadvantages these optimized plans call for further and broader exploration.

Automatic Radiotherapy Planning for Glioblastoma Radiotherapy With Sparing of the Hippocampus and nTMS-Defined Motor Cortex.

BACKGROUND: Navigated transcranial magnetic stimulation (nTMS) of the motor cortex has been successfully implemented into radiotherapy planning by a number of studies. Furthermore, the hippocampus has been identified as a radiation-sensitive structure meriting particular sparing in radiotherapy. This study assesses the joint protection of these two eloquent brain regions for the treatment of glioblastoma (GBM), with particular emphasis on the use of automatic planning. PATIENTS AND METHODS: Patients with motor-eloquent brain glioblastoma who underwent surgical resection after nTMS mapping of the motor cortex and adjuvant radiotherapy were retrospectively evaluated. The radiotherapy treatment plans were retrieved, and the nTMS-defined motor cortex and hippocampus contours were added. Four additional treatment plans were created for each patient: two manual plans aimed to reduce the dose to the motor cortex and hippocampus by manual inverse planning. The second pair of re-optimized plans was created by the Auto-Planning algorithm. The optimized plans were compared with the "Original" plan regarding plan quality, planning target volume (PTV) coverage, and sparing of organs at risk (OAR). RESULTS: A total of 50 plans were analyzed. All plans were clinically acceptable with no differences in the PTV coverage and plan quality metrics. The OARs were preserved in all plans; however, overall the sparing was significantly improved by Auto-Planning. Motor cortex protection was feasible and significant, amounting to a reduction in the mean dose by >6 Gy. The dose to the motor cortex outside the PTV was reduced by >12 Gy (mean dose) and >5 Gy (maximum dose). The hippocampi were significantly improved (reduction in mean dose: ipsilateral >6 Gy, contralateral >4.6 Gy; reduction in maximum dose: ipsilateral >5 Gy, contralateral >5 Gy). While the dose reduction using Auto-Planning was generally better than by manual optimization, the radiated total monitor units were significantly increased. CONCLUSION: Considerable dose sparing of the nTMS-motor cortex and hippocampus could be achieved with no disadvantages in plan quality. Auto-Planning could further contribute to better protection of OAR. Whether the improved dosimetric protection of functional areas can translate into improved quality of life and motor or cognitive performance of the patients can only be decided by future studies.

Preoperative Navigated Transcranial Magnetic Stimulation Improves Gross Total Resection Rates in Patients with Motor-Eloquent High-Grade Gliomas: A Matched Cohort Study.

BACKGROUND: Navigated transcranial magnetic stimulation (nTMS) is an established, noninvasive tool to preoperatively map the motor cortex. Despite encouraging reports from few academic centers with vast nTMS experience, its value for motor-eloquent brain surgery still requires further exploration. OBJECTIVE: To further elucidate the role of preoperative nTMS in motor-eloquent brain surgery. METHODS: Patients who underwent surgery for a motor-eloquent supratentorial glioma or metastasis guided by preoperative nTMS were retrospectively reviewed. The nTMS group (n = 105) was pair-matched to controls (non-nTMS group, n = 105). Gross total resection (GTR) and motor outcome were evaluated. Subgroup analyses including survival analysis for WHO III/IV glioma were performed. RESULTS: GTR was significantly more frequently achieved in the entire nTMS group compared to the non-nTMS group (P = .02). Motor outcome did not differ (P = .344). Bootstrap analysis confirmed these findings. In the metastases subgroup, GTR rates and motor outcomes were equal. In the WHO III/IV glioma subgroup, however, GTR was achieved more frequently in the nTMS group (72.3%) compared to non-nTMS group (53.2%) (P = .049), whereas motor outcomes did not differ (P = .521). In multivariable Cox-regression analysis, prolonged survival in WHO III/IV glioma was significantly associated with achievement of GTR and younger patient age but not nTMS mapping. CONCLUSION: Preoperative nTMS improves GTR rates without jeopardizing neurological function. In WHO III/IV glioma surgery, nTMS increases GTR rates that might translate into a beneficial overall survival. The value of nTMS in the setting of a potential survival benefit remains to be determined.

Establishment of Submillisievert Abdominal CT Protocols With an In Vivo Swine Model and an Anthropomorphic Phantom.

OBJECTIVE. The purpose of this study was to evaluate radiation dose, effective dose, and image quality of different low-dose abdominal CT protocols in a swine model and an anthropomorphic phantom using a third-generation dual-source CT scanner. MATERIALS AND METHODS. Four different abdominal low-dose protocols were established using a swine model and were regarded as diagnostic by two experienced radiologists on the basis of clarity and sharpness of anatomic structures. General image conditions such as noise and spatial resolution as well as diagnostic acceptability and artifacts were evaluated. Objective image quality was determined by measuring signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in different anatomic locations. To evaluate the effective dose, thermoluminescent dosimeter (TLD) measurements were repeated in a phantom. RESULTS. Diagnostic acceptability, spatial resolution, and noise were rated as optimal in all four protocols, which were therefore regarded as diagnostic. We found no statistically significant differences in SNR or CNR for the four low-dose protocols. Effective dose determined from the phantom measurements did not exceed 0.33 mSv for any protocol. Overall evaluation of the 86 TLD measurements for the four low-dose protocols revealed a statistically significant difference in radiation dose (p < 0.0001), showing that the dual-source protocol had the lowest radiation dose. CONCLUSION. Submillisievert abdominal CT is feasible with good image quality and doses even lower than conventional abdominal radiography. Our dual-source protocol achieved the lowest dose, which further shows that dual-source imaging is possible in the submillisievert range without additional dose.

Local Stage Dependent Necessity of Radiation Therapy in Rhabdoid Tumors of the Kidney (RTK).

PURPOSE: Rhabdoid tumor of the kidney (RTK) is one of the most aggressive childhood renal tumors. Overall survival ranges from 22% to 47%. The indication for radiation therapy (RT) in usually very young patients is an ongoing discussion. Recent protocols recommend RT independent of local stage, the latter being a good discriminator in other childhood kidney tumors. In this study, we analyze the evidence for RT in regard to risk factors, including tumor stage. METHODS AND MATERIALS: This study analyzed 58 patients with RTK from Austria, Switzerland, and Germany treated in the framework of 4 consecutive, prospective renal/rhabdoid tumor studies from 1991 to 2014. All treatment protocols included multimodality treatment, including high-intensity chemotherapy, surgery, and RT. RESULTS: Local stage distribution was not applicable, I, II, and III in 1, 6, 11, and 40, respectively. Twenty-nine (50%) patients had stage IV disease at diagnosis. Thirty-seven patients (64%) achieved complete remission, and 49% (18/37) relapsed. Thirty-four patients (60%) patients had progressive disease and died, 17 had local disease, 10 had combined disease, and 7 had distant disease; 2 treatment-related deaths were reported (3%). Twenty-one patients received RT during first-line treatment, 18 of them to all involved sites. Eight of the 34 cases of progressive disease occurred in irradiated patients. The local failure rate of treated patients with local stage II or III disease was 29% (6/18) in patients irradiated to all sites compared with 68% (15/22) in nonirradiated patients. One of 6 stage I patients received RT, and 1 patient experienced distant relapse (2-year progression-free and overall survival both 83% ± 15%). Progression-free survival for local stage II and III disease treated with RT, adjusted for early relapse or treatment abandonment, was 67% ± 11%, compared with 15% ± 7% without RT (P < .0001). CONCLUSION: The 68% local failure rate in nonirradiated patients underlines the importance of local treatment. Our experience supports the use of RT for local control in higher stage disease. In contrast, no local relapse in 6 local stage I patients, including 5 nonirradiated patients, suggests omission of RT in this favorable subset of usually infant patients with RTK.

Monte-Carlo simulation of the Siemens Artiste linear accelerator flat 6 MV and flattening-filter-free 7 MV beam line.

The aim of our work is to provide the up-to-now missing information on the Siemens Artiste FFF 7 MV beam line using a Monte-Carlo model fit to the realistic dosimetric measurements at the linear accelerator in clinical use at our department. The main Siemens Artiste 6MV and FFF 7MV beams were simulated using the Geant4 toolkit. The simulations were compared with the measurements with an ionization chamber in a water phantom to verify the validation of simulation and tuning the primary electron parameters. Hereafter, other parameters such as surface dose, spectrum, electron contamination, symmetry, flatness/unflatness, slope, and characteristic off-axis changes were discussed for both Flat and FFF mode. The mean electron energy for the FFF beam was 8.8 MeV and 7.5 MeV for Flat 6 MV, the spread energy and spot size of the selected Gaussian distribution source were 0.4 MeV and 1mm, respectively. The dose rate of the FFF beam was 2.8 (2.96) times higher than for the flattened beam for a field size of 10×10 (20×20) cm2. The electron contamination has significant contribution to the surface dose especially for the flattened beam. The penumbra, surface dose and the mean energy of photons decrease by removing the flattening filter. Finally, the results show that off-axis changes have no strong effect on the mean energy of FFF beams, while this effect was more considerable for the flattened beam.

Image guidance and positioning accuracy in clinical practice: influence of positioning errors and imaging dose on the real dose distribution for head and neck cancer treatment.

BACKGROUND: Modern radiotherapy offers the possibility of highly accurate tumor treatment. To benefit from this precision at its best, regular positioning verification is necessary. By the use of image-guided radiotherapy and the application of safety margins the influence of positioning inaccuracies can be counteracted. In this study the effect of additional imaging dose by set-up verification is compared with the effect of dose smearing by positioning inaccuracies for a collective of head-and-neck cancer patients. METHODS: This study is based on treatment plans of 40 head-and-neck cancer patients. To evaluate the imaging dose several image guidance scenarios with different energies, techniques and frequencies were simulated and added to the original plan. The influence of the positioning inaccuracies was assessed by the use of real applied table shifts for positioning. The isocenters were shifted back appropriately to these values to simulate that no positioning correction had been performed. For the single fractions the shifted plans were summed considering three different scenarios: The summation of only shifted plans, the consideration of the original plan for the fractions with set-up verification, and the addition of the extra imaging dose to the latter. For both effects (additional imaging dose and dose smearing), plans were analyzed and compared considering target coverage, sparing of organs at risk (OAR) and normal tissue complication probability (NTCP). RESULTS: Daily verification of the patient positioning using 3D imaging with MV energies result in non-negligible high doses. kV imaging has only marginal influence on plan quality, primarily related to sparing of organs at risk, even with daily 3D imaging. For this collective, sparing of organs at risk and NTCP are worse due to potential positioning errors. CONCLUSION: Regular set-up verification is essential for precise radiation treatment. Relating to the additional dose, the use of kV modalities is uncritical for any frequency and technique. Dose smearing due to positioning errors for this collective mainly resulted in a decrease of OAR sparing. Target coverage also suffered from the positioning inaccuracies, especially for individual patients. Taking into account both examined effects the relevance of an extensive IGRT is clearly present, even at the expense of additional imaging dose and time expenditure.

Imaging dose and secondary cancer risk in image-guided radiotherapy of pediatric patients.

BACKGROUND: Daily image-guided radiotherapy (IGRT) can contribute to cover extended body volumes with low radiation dose. The effect of additional imaging dose on secondary cancer development is modelled for a collective of children with Morbus Hodgkin. METHODS: Eleven radiotherapy treatment plans from pediatric patients with Hodgkin's lymphoma were retrospectively analyzed, including imaging dose from scenarios using different energies (kV/MV) and planar/cone-beam computed tomography (CBCT) techniques. In addition to assessing the effect of imaging dose on organs at risk, the excess average risk (EAR) for developing a secondary carcinoma of the lung or breast was modelled. RESULTS: Although the variability between the patients is relatively large due to the different target volumes, the additional EAR due to imaging can be consistently determined. For daily 6MV CBCT, the EAR for developing a secondary cancer at age 50 is over 3 cases per 104 PY (patient-years) for the female breast and 0.7-0.8 per 104 PY for the lungs. This can be decreased by using only planar images (< 1 per 104 PY for the breast and 0.1 for the lungs). Similar values are achieved by daily 360° kV CBCT (0.44-0.57 per 104 PY for the breast and 0.08 per 104 PY for the lungs), which is again reduced for daily 200° kV CBCT (0.02 per 104 PY for the lungs and 0.07-0.08 per 104 PY for the breast). These values increase if an older attained age is considered (e.g., for 70 years, by a factor of four for the lungs). CONCLUSIONS: Daily imaging can be performed with an additional secondary cancer risk of less than 1 per 104 PY if kV CBCT is applied. If MV modalities must be chosen, a similar EAR can be achieved with planar images. A further reduction in risk is possible if the imaging geometry allows for sparing of the breast by a partial rotation underneath the patient.

Image guidance in clinical practice - Influence of positioning inaccuracy on the dose distribution for prostate cancer.

BACKGROUND: In order to consider potential positioning errors there are different recipes for safety-margins for CTV-to-PTV expansion. The aim of this study is to simulate the effect of positioning inaccuracy with clinically realistic patient treatment plans. METHODS: For a collective of 40 prostate patients, the isocenter was shifted back appropriately to the applied table shifts after positioning verification, simulating that no positioning correction had been performed and the treatment plans were recalculated. All the treatment fractions with the appropriate isocenter-shifts were added to yield a new plan considering two scenarios:Afterwards all plans were analysed and compared with each other regarding target coverage, sparing of organs at risk (OAR) and normal tissue complication probability (NTCP). RESULTS: Dose distributions and especially DVH show a deterioration of the target-coverage caused by the positioning inaccuracy. Deviations in dose at a single point can reach values of over 10 Gy. In single cases minimum plan agreement only achieved 66% pass within 3% local dose for the realistic case. Organs at risk and NTCP analysis result in a slightly better sparing of the rectum. Measures of quality like homogeneity and conformity differ just minimally regarding the different scenarios. CONCLUSION: PTV-coverage suffers markedly by the positioning uncertainties, the shifted plans are in large parts clinically not acceptable. Surprisingly sparing of the OAR is not negatively affected by potential positioning errors for this prostate collective.

Abdominal imaging dose in radiology and radiotherapy - Phantom point dose measurements, effective dose and secondary cancer risk.

PURPOSE: To compare abdominal imaging dose from 3D imaging in radiology (standard/low-dose/dual-energy CT) and radiotherapy (planning CT, kV cone-beam CT (CBCT)). METHODS: Dose was measured by thermoluminescent dosimeters (TLD's) placed at 86 positions in an anthropomorphic phantom. Point, organ and effective dose were assessed, and secondary cancer risk from imaging was estimated. RESULTS: Overall dose and mean organ dose comparisons yield significantly lower dose for the optimized radiology protocols (dual-source and care kV), with an average dose of 0.34±0.01 mGy and 0.54±0.01 mGy (average ±â€¯standard deviation), respectively. Standard abdominal CT and planning CT involve considerably higher dose (13.58 ±â€¯0.18 mGy and 18.78±0.27 mGy, respectively). The CBCT dose show a dose fall-off near the field edges. On average, dose is reduced as compared with the planning or standard CT (3.79 ±â€¯0.21 mGy for 220° rotation and 7.76 ±â€¯0.37 mGy for 360°), unless the high-quality setting is chosen (20.30 ±â€¯0.96 mGy). The mean organ doses show a similar behavior, which translates to the estimated secondary cancer risk. The modelled risk is in the range between 0.4 cases per million patient years (PY) for the radiological scans dual-energy and care kV, and 300 cases per million PY for the high-quality CBCT setting. CONCLUSIONS: Modern radiotherapy imaging techniques (while much lower in dose than radiotherapy), involve considerably more dose to the patient than modern radiology techniques. Given the frequency of radiotherapy imaging, a further reduction in radiotherapy imaging dose appears to be both desirable and technically feasible.

Retrospective analysis of stereotactic ablative radiotherapy (SABR) for metastatic lung lesions (MLLs) in comparison with a contemporaneous cohort of primary lung lesions (PLLs).

BACKGROUND: The net benefit from local ablative therapy for pulmonary oligometastases remains unknown. The outcomes of stereotactic ablative radiotherapy (SABR) for metastatic lung lesions (MLLs) were analyzed retrospectively and compared with those of SABR for primary lung lesions (PLLs). METHODS: Medical records of patients treated with lung SABR between 2011 and 2014 were retrospectively reviewed. Basic patient, lesion and treatment characteristics were compared using the Pearson chi-square test for categorical and Mann-Whitney U test for continuous variables. To estimate the rates of local control (LC), progression-free survival (PFS), survival after the first progression post-SABR (SAPF) and overall survival (OS), the Kaplan-Meier method was used, and the differences between groups were assessed by means of the log rank test. The uni- and multivariate Cox proportional hazards regression model was used to identify predictive factors for these endpoints. RESULTS: Twenty-nine MLLs in 18 consecutive patients and 51 PLLs in 42 patients were treated stereotactically and included in the study. Median follow-up was 14 months (range, 4-40 months). Although patients with MLLs had a significantly better cardiopulmonary function (P=0.0001), more conservative dose-fractionation schedules were prescribed (P=0.0001), but this did not result in a significant difference in LC (P=0.98), PFS (P=0.06) and OS (P=0.14). Multivariate analysis revealed that the dose per fraction (≥ or <12 Gy) was an independent predictor for LC (P=0.02) and PFS (P=0.01) for the whole population, and for PFS (P=0.02) in the PLLs group. Late toxicities ≥ G2 occurred in six patients with PLLs, compared with none in the metastatic group. CONCLUSIONS: SABR for MLLs was as successful as for PLLs with respect to LC and OS with lower long-term toxicity in patients with MLLs. Dose per fraction ≥12 Gy turned out to be an independent, favorable prognostic factor.

Radiotherapy of painful heel spur with two fractionation regimens : Results of a randomized multicenter trial after 48 weeks' follow-up.

BACKGROUND: In this randomized multicenter trial, we compared the effect of a lower single dose of 0.5 Gy vs. a standard single dose of 1 Gy concerning pain relief and quality of life, while maintaining a uniform total dose of 6 Gy. On the basis of laboratory observations, the lower single dose would be expected to be more effective. PATIENTS AND METHODS: A total of 127 patients suffering from painful heel spur were randomized: Patients in the standard group were treated with single fractions of 6 × 1 Gy twice a week, while the experimental group was treated with single fractions of 12 × 0.5 Gy three times a week. Patients who did not show satisfactory pain relief after 12 weeks were offered re-irradiation with the standard dose. The study's primary endpoints were pain relief and quality of life. Therapy results were evaluated and compared based on follow-up examinations after 12 and 48 weeks. RESULTS: The data of 117 patients could be evaluated. There was no significant difference between the groups concerning the results of a visual analogue scale (VAS), Calcaneodynia Score (CS), and the somatic scale of the 12-Item Short-Form Health Survey(SF-12). Patients undergoing re-irradiation showed a significant benefit concerning pain relief. Their total outcome was comparable to patients showing a good response from the beginning. No relevant acute or chronic side effects were recorded. CONCLUSION: Both patient groups showed good results concerning pain relief. A fractionation schedule of 12 × 0.5 Gy was not superior to the current standard dose of 6 × 1 Gy. Further trials are necessary to explore the best fractionation schedule.

Influence of daily imaging on plan quality and normal tissue toxicity for prostate cancer radiotherapy.

BACKGROUND: Modern radiotherapy offers various possibilities for image guided verification of patient positioning. Different clinically relevant IGRT (image guided radiotherapy) scenarios were considered with regard to their influence on dosimetric plan quality and normal tissue complication probability (NTCP). METHODS: This study is based on treatment plans of 50 prostate patients. We evaluate the clinically performed IGRT and simulate the influence of different daily IGRT scenarios on plan quality. Imaging doses of planar and cone-beam-CT (CBCT) images for three different energies (6 MV, 1 MV and 121 kV) were added to the treatment plans. The plan quality of the different scenarios was assessed by a visual inspection of the dose distribution and dose-volume-histogram (DVH) and a statistical analysis of DVH criteria. In addition, an assessment of the normal tissue complication probability was performed. RESULTS: Daily 1MV-CBCTs result in undesirable high dose regions in the target volume. The DVH shows that the scenarios with actual imaging performed, daily kV-CBCT and daily 6MV imaging (1x CBCT, 4x planar images per week) do not differ exceedingly from the original plan; especially imaging with daily kV-CBCT has little influence to the sparing of organs at risk. In contrast, daily 1MV- CBCT entails an additional dose of up to two fraction doses. Due to the additional dose amount some DVH constraints for plan acceptability could no longer be satisfied, especially for the daily 1MV-CBCT scenario. This scenario also shows increased NTCP for the rectum. CONCLUSION: Daily kV-CBCT has negligible influence on plan quality and is commendable for the clinical routine. If no kV-modality is available, a daily IGRT scenario with one CBCT per week and planar axial images on the other days should be preferred over daily MV-CBCT.

mARC Treatment of Hypopharynx Carcinoma with Flat and Flattening-Filter-Free Beam Energies - A Planning Study.

BACKGROUND: The recently implemented mARC-rotation-technique is capable to deliver high dose rate bursts. For the case of hypopharynx cancer plans we evaluate whether the mARC can achieve an advantage in treatment time in comparison to IMRT. These plans consider two arcs with flat and flattening filter free (FFF) beam energies. MATERIALS AND METHODS: For 8 hypopharynx-cancer patients step-and-shoot-IMRT and mARC plans were created retrospectively using flat and FFF beam energy. The comparison of the plan scenarios considered measures of quality for PTV coverage and sparing of organs at risk. All plans were irradiated on an anthromorphic phantom equipped with thermoluminescent dosimeters to measure scattered dose and treatment times. RESULTS: A visual comparison of the dose distribution did not show a marked preference for either technique or energy. The statistical evaluation yielded significant differences in favor of the mARC technique and the FFF energy. Scattered dose could be decreased markedly by the use of the mARC technique. Treatment times could be reduced up to 3 minutes with the use of mARC in comparison to IMRT. The high dose rate energy results in another time advantage of about 1 minute. CONCLUSIONS: All four plan scenarios yielded equally good quality plans. A combination of the mARC technique with FFF 7 MV high dose rate resulted in a decrease of treatment times from about 9 minutes to 5-6 minutes in comparison to 6 MV IMRT.