Full bladder, empty rectum? Revisiting a paradigm in the era of adaptive radiotherapy.

BACKGROUND AND PURPOSE: Many patients find it challenging to comply with instructions regarding rectum and bladder filling during pelvic radiotherapy. With the implementation of online adaptive radiotherapy, the reproducibility of organ volumes is no longer a prerequisite. This study aims to analyze the sparing of the bladder and the posterior rectum wall (PRW) in conditions of full versus empty bladder and rectum. METHODS: 280 fractions from 14 patients with prostate cancer who underwent adaptive radiotherapy using the Varian Ethos system were analyzed post-hoc. Various metrics for the bladder and PRW were correlated with respect to organ volume. RESULTS: Our analysis quantitatively confirms the advantage of a full bladder during radiotherapy, as metrics V48Gy and V40Gy significantly inversely correlate with bladder filling for each patient individually. While bladder volume did not show a gradual decrease over the course of radiotherapy, it was observed to be higher during planning CT scans compared to treatment sessions. A full rectum condition either significantly improved (in 2 out of 7 patients) or at least did not impair (in 5 out of 7 patients) PRW sparing, as represented by the V30Gy metric, when patients were compared individually. The average V30Gy across all patients demonstrated a significant improvement in PRW sparing for the full rectum condition, with a [Formula: see text]-value of 0.039. CONCLUSION: Despite the implementation of adaptive therapy, maintaining a high bladder filling remains important. However, the recommendation for rectum filling can be abandoned, as reproducibility is not critical for adaptive radiotherapy and no dosimetric advantage per se is associated with an empty rectum. Patients may even be encouraged not to void their bowels shortly before treatment, as long as this is tolerated over the treatment session.

Effect of different optimization parameters in single isocenter multiple brain metastases radiosurgery.

PURPOSE: Automated treatment planning for multiple brain metastases differs from traditional planning approaches. It is therefore helpful to understand which parameters for optimization are available and how they affect the plan quality. This study aims to provide a reference for designing multi-metastases treatment plans and to define quality endpoints for benchmarking the technique from a scientific perspective. METHODS: In all, 20 patients with a total of 183 lesions were retrospectively planned according to four optimization scenarios. Plan quality was evaluated using common plan quality parameters such as conformity index, gradient index and dose to normal tissue. Therefore, different scenarios with combinations of optimization parameters were evaluated, while taking into account dependence on the number of treated lesions as well as influence of different beams. RESULTS: Different scenarios resulted in minor differences in plan quality. With increasing number of lesions, the number of monitor units increased, so did the dose to healthy tissue and the number of interlesional dose bridging in adjacent metastases. Highly modulated cases resulted in 4-10% higher V10% compared to less complex cases, while monitor units did not increase. Changing the energy to a flattening filter free (FFF) beam resulted in lower local V12Gy (whole brain-PTV) and even though the number of monitor units increased by 13-15%, on average 46% shorter treatment times were achieved. CONCLUSION: Although no clinically relevant differences in parameters where found, we identified some variation in the dose distributions of the different scenarios. Less complex scenarios generated visually more dose overlap; therefore, a more complex scenario may be preferred although differences in the quality metrics appear minor.

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.

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.

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.

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.

Customized individual applicators for endocavitary brachytherapy in patients with cancers of the nasal cavity, sinonasal region and nasopharynx.

Brachytherapy has become an established therapeutic regimen for primary, persistent, recurrent and metastatic tumour disease in the head and neck region. This study presents the authors' preliminary experience with intracavitary brachytherapy by means of an individual silicone applicator in the treatment of patients with nasal, sinonasal, orbital and nasopharyngeal cancer. Between January 2001 and January 2013, twenty patients with cancer of the nasal cavity, the paranasal sinuses and nasopharynx underwent surgery and intracavitary brachytherapy with the aid of an individually manufactured silicone applicator in the Department of Otolaryngology, Head and Neck Surgery and in the Department of Radiotherapy and Radiooncology at the Saarland University Medical Center of Homburg, Germany. The tumour was localized in the nasal cavity/paranasal sinuses (15) affecting the orbit twice and the nasopharynx (5). There were 14 patients with squamous cell carcinoma, 2 patients with mixed tumours and one patient with adenocarcinoma, adenoid cystic carcinoma, mucosal melanoma or plasmocytoma. The majority of the patients presented with advanced disease (T3 or T4 tumours). In 18/20 patients, brachytherapy was performed as a boost technique, in the remaining two solely because of a previous radiation series. All surgical interventions were performed endonasally. Three to six weeks after surgery, a cast of the nasal cavity was created under general anaesthesia. Subsequently, an individual brachytherapy silicon applicator with two to four plastic tubes was manufactured. The radiation therapy was applied using the Ir-192 high-dose-rate-afterloading method (total dose 10-20 Gy) in two to five sessions, additionally in 18/20 patients a percutaneous radiotherapy with a total dose of 30-60 Gy was applied. After a mean duration of follow-up of 2 years, 7/20 patients experienced a local progression, 5/19 a regional recurrence in the neck nodes and 4/19 distant metastases. The 2-year survival was 57.3 %. No serious complications were reported. The silicone applicator was well tolerated by all patients. Because of the complexity of the sinonasal anatomy with the finding of mainly advanced tumours, the presented individual silicone brachytherapy applicator has proven to be useful and meaningful for endocavitary brachytherapy of malignancies of the nasal cavities, paranasal sinuses and nasopharynx.

Image quality and dose distributions of three linac-based imaging modalities.

BACKGROUND AND PURPOSE: Linac-based patient imaging is possible with a variety of techniques using different photon energies. The purpose of this work is to compare three imaging systems operating at 6 MV, flattening free filter (FFF) 1 MV, and 121 kV. PATIENTS AND METHODS: The dose distributions of all pretreatment set-up images (over 1,000) were retrospectively calculated on the planning computed tomography (CT) images for all patients with prostate and head-and-neck cancer treated at our institution in 2013. We analyzed the dose distribution and the dose to organs at risk. RESULTS: For head-and-neck cancer patients, the imaging dose from 6-MV cone beam CT (CBCT) reached maximum values at around 8 cGy. The 1-MV CBCT dose was about 63-79 % of the 6-MV CBCT dose for all organs at risk. Planar imaging reduced the imaging dose from CBCT to 30-40 % for both megavoltage modalities. The dose from the kilovoltage CBCT was 4-10 % of the 6-MV CBCT dose. For prostate cancer patients, the maximum dose from 6-MV CBCT reached 13-15 cGy, and was reduced to 66-73 % for 1 MV. Planar imaging reduces the MV CBCT dose to 10-20 %. The kV CBCT dose is 15-20 % of the 6-MV CBCT dose, slightly higher than the dose from MV axes. The dose distributions differ markedly in response to the different beam profiles and dose-depth characteristics.

VMAT to arclet plan conversion in a treatment planning system : Feasibility and dosimetric relationship between VMAT, arclet, and stationary fields.

AIM: The aim of this study was to make dynamic rotation treatment with mARC available for the non-dedicated Philips Pinnacle treatment planning system by converting SmartArc plans, offering insight into the relationship between SmartArc, mARC, and stationary field irradiation. METHODS: A scripting solution is presented that can be run in the Pinnacle system. This allows for the conversion of SmartArc plans into mARC format. The dose distribution of the converted mARC plan can be evaluated both in the form of a "real" mARC plan with arclets and-as is generally done in treatment planning systems certified for mARC planning-by approximating the arclets as stationary fields. We present the proof of principle and dosimetric comparisons. RESULTS: The converted plans were irradiated without problems. For the measured 3D dose distributions, on average over 90 % points agreed with the calculated dose distributions (mARC and stationary field plans) within the gamma criteria of 3 % deviation in the local dose, 3-mm distance to agreement, for all dose values above 10 % of the maximum. The agreement between the three calculated dose distributions (SmartArc with both converted plans) was above 87 % (above 92 % when comparing mARC with stationary fields). CONCLUSION: Our solution offers the possibility of mARC planning in Pinnacle. The dose comparisons furthermore prove that the dosimetric differences between SmartArc and mARC, when appropriately translated, are minor.

Commissioning and first clinical application of mARC treatment.

BACKGROUND: The modulated arc (mARC) technique has recently been introduced for Siemens ARTISTE linear accelerators. We present the first experiences with the commissioning of the system and first patient treatments. PATIENTS AND METHODS: Treatment planning and delivery are presented for the Prowess Panther treatment planning system or, alternatively, an in-house code. Dosimetric verification is performed both by point dose measurements and in 3D dose distribution. RESULTS: Depending on the target volume, one or two arcs can be used to create highly conformal plans. Dosimetric verification of the converted mARC plans with step-and-shoot plans shows deviations below 1 % in absolute point dose; in the 3D dose distribution, over 95 % of the points pass the 3D gamma criteria (3 % deviation in local dose and 3 mm distance to agreement for doses > 20 % of the maximum). Patient specific verification of the mARC dose distribution with the calculations has a similar pass rate. Treatment times range between 2 and 5 min for a single arc. CONCLUSIONS: To our knowledge, this is the first report of clinical application of the mARC technique. The mARC offers the possibility to save significant amounts of time, with single-arc treatments of only a few minutes achieving comparable dose distribution to IMRT plans taking up to twice as long.

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.

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.

Beam properties and stability of a flattening-filter free 7 MV beam-an overview.

PURPOSE: Several works have recently focused on flattening-filter-free (FFF) beams of linear accelerators of various companies (in particular, Varian and Elekta), but no overview as yet exists for the flattening-filter free 7XU beam (Siemens Artiste). METHODS: Dosimetric properties of the 7XU beam were measured in May and September 2011. We present depth dose curves and beam profiles, output factors, and MLC transmission and assess the stability of the measurements. The 7XU beam was commissioned in the Pinnacle[superscript three] treatment planning system (TPS), and modeling results including the spectrum are presented. RESULTS: The percent depth dose curve of the 7XU beam is similar to the flat 6X beam line, with a slightly smaller surface dose. The beam profiles show the characteristic shape of flattening-filter free beams, with deviations between measurements of generally less than 1%. The output factors of the 7XU beam decrease more slowly than for the 6X beam. The MLC transmission is comparable but slightly less for the 7XU beam. The 7XU beam can be adequately modeled by the Pinnacle[superscript three] TPS, with successful dosimetric verification. The spectrum of the 7XU beam has lower photon fluence up to approximately 2.5 MeV and higher fluence beyond, with a slightly higher mean energy. CONCLUSIONS: The 7XU beam has been commissioned for clinical use after successful modeling, stability checks, and dosimetric verification.

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.

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.

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.