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Background and Purpose: Early-stage Hodgkin lymphoma (HL) is a highly curable disease but the treatment can induce late complications many years later. Irradiation of the healthy heart is inevitable during radiation treatment of mediastinal sites. We developed a novel method to induce a prolonged apnea-like state that can help decrease the dose to organs at risk during radiation therapy. We present the results of the first 8 HL patients treated routinely with percussion assisted radiation therapy (PART) in our clinic., Material and Methods: We used a newly developed high-frequency non-invasive ventilation system to suppress respiratory motion for prolonged periods and push the heart away from the treated volume., Results: All 8 patients were able to rapidly learn the technique and had an advantage to be treated by PART. We lowered the mean heart dose by an average of 3 Gy with similar target coverage compared to a classical free breathing treatment plan. They were all treated for 15 radiotherapy sessions by PART without any notable side effects., Conclusions: Percussion assisted radiation therapy can be used routinely to reduce the dose to the heart in Hodgkin lymphoma., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019. Published by Elsevier B.V.)

Purpose: To investigate the impact of respiratory motion in the treatment margins for lung SBRT frameless treatments and to validate our treatment margins using 4D CBCT data analysis., Methods: Two hundred and twenty nine fractions with early stage NSCLC were retrospectively analyzed. All patients were treated in frameless and free breathing conditions. The treatment margins were calculated according to van Herk equation in Mid-Ventilation. For each fraction, three 4D CBCT scans, pre- and postcorrection, and posttreatment, were acquired to assess target baseline shift, target localization accuracy and intra-fraction motion errors. A bootstrap analysis was performed to assess the minimum number of patients required to define treatment margins., Results: The retrospectively calculated target-baseline shift, target localization accuracy and intra-fraction motion errors agreed with the literature. The best tailored margins to our cohort of patients were retrospectively computed and resulted in agreement with already published data. The bootstrap analysis showed that fifteen patients were enough to assess treatment margins., Conclusions: The treatment margins applied to our patient's cohort resulted in good agreement with the retrospectively calculated margins based on 4D CBCT data. Moreover, the bootstrap analysis revealed to be a promising method to verify the reliability of the applied treatment margins for safe lung SBRT delivery., (© 2020 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Purpose: To validate a delivery quality assurance (DQA) protocol for tomotherapy based on the measurement of the leaf open times (LOTs). In addition, to show the correlation between the mean relative LOT discrepancy and the dose deviation in the planning target volume (PTV)., Materials and Methods: We used a LOT measurement algorithm presented in a previous work on our two tomotherapy treatment units (TOMO1 and TOMO2). We generated TomoPhant plans with intentional random LOT discrepancies following Gaussian distributions of -6%, -4%, -2%, 2%, 4%, and 6%. We irradiated them on the Cheese Phantom with two ion chambers and collected the raw data on both our treatment units. Using the raw data, we measured the actual LOTs and verified that the induced discrepancies were highlightable. Then, we calculated the actual dose using Accuray's standalone dose calculator and verified that the calculated dose agreed with the ion chamber measurement. We randomly chose 60 clinical treatment plans, delivered them in air, and collected the raw detector data. We measured the actual LOTs from the raw data and calculated the corresponding dose distributions using Accuray's standalone dose calculator. We assessed the Pearson coefficient correlation of the deviation between expected and actual dose in the PTV (a) with the mean relative LOT discrepancy and (b) with the γ-index pass rate for different tolerances., Results: The mean relative discrepancy between actual (measured by the algorithm) and expected LOTs on the modified TomoPhant plans was 1.10 ± 0.05% on TOMO1 and 0.02 ± 0.03% on TOMO2, respectively. The agreement between measured and calculated dose was 0.2 ± 0.3% on TOMO1 and 0.1 ± 0.3% on TOMO2, respectively. On clinical plans, the means of the relative LOT discrepancies ranged from -3.0 % to 1.4%. The dose deviation in the PTVs ranged from -1.6% to 2.4%. The Pearson coefficient correlation between the mean relative LOT discrepancy and the dose deviation in the PTV was 0.76 (P ≈ 10 -15 ) on TOMO1 and 0.65 (P ≈ 10 -10 ) on TOMO2, respectively. There was no correlation between the γ-index pass rate and the dose deviation in the PTV., Conclusion: The method made it possible to measure and to correctly highlight the LOT discrepancies on the TomoPhant plans. The dose subsequently calculated was accurate. On clinical plans, the mean LOT discrepancy correlated with the dose deviation in the PTV. This makes the mean LOT discrepancy a handy indicator of the plan quality., (© 2020 American Association of Physicists in Medicine.)

Ventricular tachycardia (VT) caused by myocardial scaring bears a significant risk of mortality and morbidity. Antiarrhythmic drug therapy (AAD) and catheter ablation remain the cornerstone of VT management, but both treatments have limited efficacy and potential adverse effects. Stereotactic body radiotherapy (SBRT) is routinely used in oncology to treat non-invasively solid tumors with high precision and efficacy. Recently, this technology has been evaluated for the treatment of VT. This review presents the basic underlying principles, proof of concept, and main results of trials and case series that used SBRT for the treatment of VT refractory to AAD and catheter ablation., (Copyright © 2020 Jumeau, Ozsahin, Schwitter, Elicin, Reichlin, Roten, Andratschke, Mayinger, Saguner, Steffel, Blanck, Vozenin, Moeckli, Zeverino, Vallet, Herrera-Siklody, Pascale, Bourhis and Pruvot.)

Purpose: The purpose of this study was to calculate dose distributions from CyberKnife image-guided radiation therapy (IGRT) for brain, H&N, lung, and pelvis treatment regions and use them to extract the corresponding effective dose and estimate-related risk., Methods: We developed a CyberKnife IGRT kV beam model in a standard treatment planning system and validated it against measurements in heterogeneous phantoms. Five brain, five head and neck, five thorax, and 10 (five male and five female) pelvis patient computed tomographies (CTs) were contoured. The dose distribution resulting from different CyberKnife IGRT protocols was calculated. From them, the effective dose was calculated according to ICRP publication Nr 103, using the average dose to contoured organs. The corresponding risk factors were calculated. Entrance surface dose (ESD) was also calculated and compared with existing data., Results: The maximum effective dose produced by CyberKnife IGRT protocols was 0.8 mSv (brain), 1.9 mSv (H&N), 20.2 (pelvis), and 42.4 mSv (thorax) per fraction for a risk estimate of 0.004% (brain), 0.01% (H&N), 0.1% (pelvis), and 0.2% (thorax). Calculated ESD were compatible with existing data., Conclusions: Dose calculation models for CyberKnife IGRT kV beams were implemented in a clinical treatment planning system and validated in water and heterogeneous phantoms. We determined the effective dose and the related risk estimate resulting from CyberKnife IGRT protocols for brain, head and neck, thorax, and pelvis cases. The effective doses calculated for CyberKnife IGRT protocols were similar to those obtained for cone beam CT protocols on conventional C-arm linear accelerators, except for extreme irradiation conditions for thorax cases (140 kV X-ray tube tension)., (© 2020 American Association of Physicists in Medicine.)

Although cardiac metastases (CM) are more common than primary cardiac malignant tumors, they remain a rare localization of metastatic cancer. Until recently, CM were surgically treated as a palliative approach because of a lack of ablative solutions even for oligometastatic patients. Technological advances in radiation therapy (RT) in thoracic oncology have led to high precision delivery that enlarged the indications for stereotactic body radiotherapy (SBRT). To date, there are limited reports of cardiac SBRT for CM. Herein, we report a cardiac SBRT performed in curative intent for a lung cancer patient metastatic to the heart., Competing Interests: The authors report no conflict of interest related to this work. The authors alone are responsible for the content and writing of the paper., (© 2019 Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

Purpose: Preclinical studies using a new treatment modality called FLASH Radiotherapy (FLASH-RT) need a two-phase procedure to ensure minimal uncertainties in the delivered dose. The first phase requires a new investigation of the reference dosimetry lying outside the conventional metrology framework from national metrology institutes but necessary to obtain traceability, repeatability, and stability of irradiations. The second consists of performing special quality assurance procedure prior to irradiation., Materials and Methods: The Oriatron eRT6 (PMB-Alcen, France) is an experimental high dose-per-pulse linear accelerator, delivering a 6 MeV pulsed electron beam with mean dose-rates, ranging from a few Gy/min up to thousands of Gy/s. Absolute dosimetry is investigated with alanine, thermo-luminescent dosimeters (TLD) and radiochromic films as well as an ionization chamber for relative stability. The beam characteristic and dosimetry are prepared for three different setups., Results: A cross-check between alanine, films and TLD revealed a dose agreement within 3% for dose-rates between 0.078 Gy/s and 1050 Gy/s, showing that these dosimeters are suitable for absolute dosimetry for FLASH-RT. In absence of appropriate setup dependent corrections, active dosimetry can reveal dose deviations up to 15% of the prescribed dose. These differences reduce to less than 3% when our dosimetric procedure is applied., Conclusion: We developed procedures to accurately irradiate biological models. Our method is based on validated absolute dosimeters and extends their use to routine FLASH irradiations. We reached an agreement of 3% between the delivered and prescribed dose and developed the requirements needed for workflows of preclinical and clinical studies., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Over the past decades, technological advances have transformed radiation therapy (RT) into a precise and powerful treatment for cancer patients. Nevertheless, the treatment of radiation-resistant tumors is still restricted by the dose-limiting normal tissue complications. In this context, FLASH-RT is emerging in the field. Consisting of delivering doses within an extremely short irradiation time, FLASH-RT has been identified as a promising new tool to enhance the differential effect between tumors and normal tissues. Indeed, preclinical studies on various animal models and a veterinarian clinical trial have recently shown that compared to conventional dose-rate RT, FLASH-RT could control tumors while minimizing normal tissue toxicity. In the present review, we summarize the main data supporting the clinical translation of FLASH-RT and explore its feasibility, the key irradiation parameters and the potential technologies needed for a successful clinical translation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: When compared to conventional radiotherapy (RT) in pre-clinical studies, FLASH-RT was shown to reproducibly spare normal tissues, while preserving the anti-tumor activity. This marked increase of the differential effect between normal tissues and tumors prompted its clinical translation. In this context, we present here the treatment of a first patient with FLASH-RT., Material & Methods: A 75-year-old patient presented with a multiresistant CD30+ T-cell cutaneous lymphoma disseminated throughout the whole skin surface. Localized skin RT has been previously used over 110 times for various ulcerative and/or painful cutaneous lesions progressing despite systemic treatments. However, the tolerance of these RT was generally poor, and it was hypothesized that FLASH-RT could offer an equivalent tumor control probability, while being less toxic for the skin. This treatment was given to a 3.5-cm diameter skin tumor with a 5.6-MeV linac specifically designed for FLASH-RT. The prescribed dose to the PTV was 15 Gy, in 90 ms. Redundant dosimetric measurements were performed with GafChromic films and alanine, to check the consistency between the prescribed and the delivered doses., Results: At 3 weeks, i.e. at the peak of the reactions, a grade 1 epithelitis (CTCAE v 5.0) along with a transient grade 1 oedema (CTCAE v5.0) in soft tissues surrounding the tumor were observed. Clinical examination was consistent with the optical coherence tomography showing no decrease of the thickness of the epidermis and no disruption at the basal membrane with limited increase of the vascularization. In parallel, the tumor response was rapid, complete, and durable with a short follow-up of 5 months. These observations, both on normal skin and on the tumor, were promising and prompt to further clinical evaluation of FLASH-RT., Conclusion: This first FLASH-RT treatment was feasible and safe with a favorable outcome both on normal skin and the tumor., (Copyright © 2019. Published by Elsevier B.V.)

Purpose: A novel optimization algorithm (VOLO™) for robotic radiosurgery in the Precision™ treatment planning system was evaluated for different SRS/SBRT treatments and compared with the previous Sequential Optimization (SO) algorithm., Materials and Methods: Fifty cases of brain, spine, prostate and lung tumors previously optimized with SO, were re-planned with VOLO™ algorithm keeping the same prescription, collimator type and size, optimization shells, and blocking structures. The dosimetric comparison involved target coverage, conformity (CI), gradient (GI) and homogeneity indexes, specific indicators of dose to OARs and number of nodes, beams, MU and delivery time. For brain only, plans were IRIS- and MLC-based (10 each). The remaining 30 plans were all IRIS-based., Results: VOLO™ optimization was significantly superior for target coverage for prostate and spine, CI for brain, and for brain and urethra dose sparing. SO gave significantly better results for GI for prostate. VOLO™ showed a significantly steeper dose fall-off for brain MLC-based, while for prostate and spine SO was superior. For IRIS-based plans, VOLO™ significantly reduced the nodes (36%), beams (14%), and MU (31%). This led to an average reduction of delivery time of 20% (from 8% for brain to 30% for prostate). For MLC-based plans, VOLO™ significantly increased the nodes and beams (42%) keeping the same number of MU. The averaged delivery time increased by 18%., Conclusions: With respect to SO, VOLO™ optimization algorithm provided better results in terms of delivery time for IRIS-based and of quality of dose distribution for MLC-based plans, respectively., (Copyright © 2019 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Here, we highlight the potential translational benefits of delivering FLASH radiotherapy using ultra-high dose rates (>100 Gy⋅s -1 ). Compared with conventional dose-rate (CONV; 0.07-0.1 Gy⋅s -1 ) modalities, we showed that FLASH did not cause radiation-induced deficits in learning and memory in mice. Moreover, 6 months after exposure, CONV caused permanent alterations in neurocognitive end points, whereas FLASH did not induce behaviors characteristic of anxiety and depression and did not impair extinction memory. Mechanistic investigations showed that increasing the oxygen tension in the brain through carbogen breathing reversed the neuroprotective effects of FLASH, while radiochemical studies confirmed that FLASH produced lower levels of the toxic reactive oxygen species hydrogen peroxide. In addition, FLASH did not induce neuroinflammation, a process described as oxidative stress-dependent, and was also associated with a marked preservation of neuronal morphology and dendritic spine density. The remarkable normal tissue sparing afforded by FLASH may someday provide heretofore unrealized opportunities for dose escalation to the tumor bed, capabilities that promise to hasten the translation of this groundbreaking irradiation modality into clinical practice., Competing Interests: The authors declare no conflict of interest.

Stereotactic body radiotherapy (SBRT) is routinely used in oncology to treat non-invasively solid tumors with high precision and efficacy. Recently, this technology has been evaluated in the treatment of ventricular tachycardia (VT). This article presents the basic underlying principles, proofs of concept and main results of clinical studies that used SBRT for the treatment of VT., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Purpose: We developed an algorithm to measure the leaf open times (LOT) from the on-board detector (OBD) pulse-by-pulse data in tomotherapy. We assessed the feasibility of measuring the LOTs in dynamic jaw mode and validated the algorithm on machine QA and clinical data. Knowledge of the actual LOTs is a basis toward calculating the delivered dose and performing efficient phantom-less delivery quality assurance (DQA) controls of the multileaf collimator (MLC). In tomotherapy, the quality of the delivered dose depends on the correct performance of the MLC, hence on the accuracy of the LOTs., Materials and Methods: In the detector signal, the period of time during which a leaf is open corresponds to a high intensity region. The algorithm described here locally normalizes the detector signal and measures the FWHM of the high intensity regions. The Daily QA module of the TomoTherapy Quality Assurance (TQA) tool measures LOT errors. The Daily QA detector data were collected during 9 days on two tomotherapy units. The errors yielded by the method were compared to these reported by the Daily QA module. In addition, clinical data were acquired on the two units (25 plans in total), in air without attenuation material in the beam path and in vivo during a treatment fraction. The study included plans with fields of all existing sizes (1.05, 2.51, 5.05 cm). The collimator jaws were in dynamic mode (TomoEDGE TM ). The feasibility of measuring the LOTs was assessed with respect to the jaw aperture., Results: The mean discrepancy between LOTs measured by the algorithm and those measured by TQA was of 0 ms, with a standard deviation of 0.3 ms. The LOT measured by the method had thus an uncertainty of 1 ms with a confidence level of 99%. In 5.05 cm dynamic jaw procedures, the detector is in the beam umbra at the beginning and at the end of the delivery. In such procedures, the algorithm could not measure the LOTs at jaw apertures between 7 and maximum 12.4 mm. Otherwise, no measurement error due to the jaw movement was observed. No LOT measurement difference between air and in vivo data was observed either., Conclusion: The method we propose is reliable. It can equivalently measure the LOTs from data acquired in air or in vivo. It handles fully the static procedures and the 2.51 cm dynamic procedures. It handles partially the 5.05 cm dynamic procedures. The limitation was evaluated with respect to the jaw aperture., (© 2019 American Association of Physicists in Medicine.)

Introduction: Stereotactic radiosurgery (SRS) is increasingly used as a minimally invasive alternative in many neurosurgical conditions, including benign and malignant tumors, vascular malformations, and functional procedures. As for any surgical procedure, strict safety guidelines and checklists are necessary to avoid errors and the inherent unnecessary complications. With regard to the former, other groups have already reported human and/or technical errors. We describe our safety checklist for Gamma Knife radiosurgical procedures., Methods: We describe our checklist protocol after an experience gained over 1500 radiosurgical procedures, using Gamma Knife radiosurgery, performed over a period of 8 years, while employing the same list of items. Minor implementation has been performed over time to address some safety issues that could be improved., Results: Two types of checklist are displayed. One is related to the indications when a specific tissue volume is irradiated, including tumors or vascular disorders. The second corresponds to functional disorders, such as when the dose is prescribed to one specific point. Using these checklists, no human error had been reported during the past 8 years of practice in our institution., Conclusion: The use of a safety checklist for SRS procedures promotes a zero-tolerance attitude for errors. This can lower the complications and is of major help in promoting multidisciplinary cooperation. We highly recommend the use of such tool, especially in the context of the increased use of SRS in the neurosurgical field.

Purpose: Image guided radiotherapy (IGRT) improves patient positioning for treatment delivery at the cost of an additional dose. This work aimed to calculate the effective dose (as an indicator of dose) for head & neck (H&N) and breast IGRT treatments by implementing dose calculation models to determine the dose distributions., Methods: The kV dose-models were created for the IGRT systems of Elekta Synergy (XVI) and Varian Clinac (OBI) linear accelerators within Philips Pinnacle TPS. Profiles and depth dose curves were measured in water. The models were validated in a CIRS thorax phantom. The IGRT dose distributions for five H&N and five breast patients were calculated. The effective dose was determined from the dose distributions following ICRP 103 recommendations. Moreover, time-saving approximations were studied in order to propose an alternative way of segmenting the tissues for a clinical implementation of the method., Results and Conclusion: The effective dose specifically associated with IGRT varied from 1 to 10mSv depending on the protocol. The kV dose-model allowed us to calculate the dose distributions from IGRT for different configurations and patients, and to determine effective dose for IGRT protocols. The clinical implementation of the method was found to reduce time and to introduce a small enough increase of uncertainty in the results to be clinically usable., (Copyright © 2018. Published by Elsevier GmbH.)

Background and Purpose: Treatment plan evaluation is a clinical decision-making problem that involves visual search and analysis in a contextually rich environment, including delineated structures and isodose lines superposed on CT data. It is a two-step process that includes visual analysis and clinical reasoning. In this work, we used eye tracking methods to gain more knowledge about the treatment plan evaluation process in radiation therapy., Materials and Methods: Dose distributions on a single transverse slice of ten prostate cancer treatment plans were presented to eight decision makers. Their eye movements and fixations were recorded with an EyeLink1000 remote eye-tracker. Total evaluation time, dwell time, number and duration of fixations on pre-segmented areas of interest were measured., Results: The main structures receiving more and longer fixations (PTV, rectum, bladder) correspond to the main trade-offs evaluated in a typical prostate plan. Radiation oncologists made more fixations on the main structures compared to the medical physicists. Radiation oncologists fixated longer on the rectum when visited for the first time, while medical physicists fixated longer on the bladder., Conclusion: Our results quantify differences in the visual evaluation patterns between radiation oncologists and medical physicists, which indicate differences in their decision making strategies., (Copyright © 2018. Published by Elsevier GmbH.)

Purpose: To study the potential of (99m)Tc-Mebrofenin hepatobiliary scintigraphy (HBS) in identifying the short-term variations of liver function after stereotactic body radiotherapy (SBRT) for liver cancers., Material and Methods: We treated with SBRT 3 patients (pts) affected by a cholangiocarcinoma and 3 patient presenting liver metastases (3x15 Gy, 4 pts; 5x8 Gy, 1 pt; 6x5 Gy, 1 pt). All patients received HBS before and 3 months after SBRT, which were co-registered with the simulation CT-scan. Structures corresponding to isodoses from 10-90 Gy were created, with intervals of 10 Gy. Finally, the variations of the mean activity (MBq) in each isodose structure have been calculated. Then, a linear regression analysis was performed., Results: We showed a linear reduction of the activity, significantly related to the delivered dose (p<0.01), and a reduction of the perfusion of 0.78% for each delivered Gy. The linear equation has predictive value of the loss of the function of 96% (R2 = 0.9605)., Conclusions: HBS could improve treatment plans for liver SBRT, by allowing the identification of the liver function variations after SBRT and, potentially, the prediction of remnant liver function after SBRT. These preliminary results should be confirmed on long-term prospective data and larger population., Competing Interests: The authors have declared that no competing interests exist.

Background and Purpose: Adjuvant radiation therapy (RT) of the whole breast (WB) is still the standard treatment for early breast cancer. A variety of radiation techniques is currently available according to different delivery strategies. This study aims to provide a comparison of six treatment planning strategies commonly adopted for breast-conserving adjuvant RT and to use the Pareto concept in an attempt to assess the degree of plan optimization., Materials and Methods: Two groups of six left- and five right-sided cases with different dose prescriptions were involved (22 patients in total). Field-in-Field (FiF), two and four Fields static-IMRT (sIMRT-2f and sIMRT-4f), Volumetric-Modulated-Arc-Therapy (VMAT), Helical Tomotherapy (HT) and Static-Angles Tomotherapy (TomoDirect™ - TD) were planned. Dose volume constraints were taken from the RTOG protocol 1005. Pareto fronts were built for a selected case to evaluate the reliability of the plan optimization process., Results: The best target dose coverage was observed for TD able to improve significantly (p < 0.01) the V95% in a range varying from 1.2% to 7.5% compared to other techniques. The V105% was significantly reduced up to 2% for HT (p < 0.05) although FiF and VMAT produced similar values. For the ipsilateral lung, V5Gy, V10Gy and Dmean were significantly lower than all other techniques (p < 0.02) for TD while the lowest value of V20Gy was observed for HT. The maximum dose to contralateral breast was significantly lowest for TD (p < 0.02) and for FiF (p < 0.05). Minor differences were observed for the heart in left-sided patients. Plans for all tested techniques were found to lie on their respective Pareto fronts., Conclusions: Overall, TD provided significantly better results in terms of target coverage and dose sparing of ipsilateral lung with respect to all other evaluated techniques. It also significantly minimized dose to contralateral breast together with FiF. Pareto front analysis confirmed the reliability of the optimization for a selected case., (© 2018 The Authors.)

Stereotactic body radiotherapy (SBRT) is an emerging non-invasive treatment in the management of ventricular tachycardia (VT). We report here an intensive care patient suffering from an electrical storm due to incessant VT, unresponsive to catheter ablation and anti-arrhythmic drugs, showing an immediate and durable response to electrophysiology-guided cardiac SBRT., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: The dosimetric differences between four radiation therapy techniques for left sided whole breast irradiation were evaluated side by side in the same patient population., Methods: Radiotherapy treatment plans were retrospectively created with Accuray TomoDirect (TD), Elekta Volumetric Modulated Arc Therapy (E-VMAT), Varian RapidArc (RA) and Field-in-field (FinF) technique for 20 patients, who had received left breast irradiation during deep-inspiration breath-hold. Dose characteristics of planning target volume and organs at risk were compared., Results: The E-VMAT, TD and RA treatment plans had higher target coverage (V95%) than FinF plans (97.7-98.3% vs. 96.6%). The low-dose spillage to contralateral breast and lung was smaller with FinF and TD (mean 0.1 and 0.3 Gy) compared to E-VMAT and RA (mean 0.6 and 0.9 Gy). E-VMAT, RA and TD techniques were more effective than FinF in sparing left anterior descending artery (mean 4.0, 4.2 and 4.7 Gy vs. 6.1 Gy, respectively)., Conclusions: In whole breast irradiation TD, E-VMAT and RA plans generated in this study achieved higher dose coverage and sparing of organs from the high dose in the vicinity of the PTV. The advantage of calculated FinF plans is the lowest dose on contralateral organs. The choice of the technique used should be weighted by each institution taking into account the dose characteristics of each technique and its fit with patient anatomy bearing in mind the increased workload of using modulated techniques and the increased beam on time., (Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Introduction: Currently, routine radiotherapy (RT) planning for locally advanced lung cancer (LC) does not take into consideration the functional state of the lung. The goal of this study was to determine if it is technically feasible to integrate the sites of pulmonary emphysema (PE) into the RT planning process., Methods: Ten patients with LC and PE treated with helical Tomotherapy© were retrospectively included. After extraction by Myrian© software based on diagnostic CT (DCT), the PE data were transferred to the treatment planning system (TPS). PE-optimized plans were performed for patients with significant PE, where the dose was focused onto the PE. We compared the PE-optimized RT plans to the initial RT plans., Results: The median dose to the planning target volume (PTV) was 52 Gy (range, 36-66) in fractions of 2-3 Gy. The median PE volume was 220 cm 3 (range: 12-1394), and six patients were eligible for a PE-optimized RT plan. Considering the lung without PE, the V20 and V30 variations were not significant (P > 0.05), the V5 decreased from 50% to 44% after re-planning (P < 0.05). The mean PTV D98 was 50 Gy versus 48 Gy (P < 0.05)., Conclusion: Focusing the RT beam flow on the PE structure rather than the healthy lung appears feasible, and may be a promising technique to help preserve pulmonary function and minimize RT-related pulmonary toxicity., (© 2016 The Royal Australian and New Zealand College of Radiologists.)

Purpose: CheckTomo is an independent dose calculation software for tomotherapy. Recently, Accuray (Accuray Inc., Sunnyvale, CA, USA) released an upgrade of its tomotherapy treatment device, called TomoEDGE Dynamic Jaws, which improves the quality of treatment plans by enhancing the dose delivery with the help of jaws motion. This study describes the upgrade of CheckTomo to that new feature., Methods: To account for the varying width and off-axis shift of dynamic jaws fields, the calculation engine of CheckTomo multiplies the treatment field profile by a penumbral filter and shifts the dose calculation grid. Penumbral filters were obtained by dividing the edge field profiles by that of the corresponding nominal field. They were sampled at widths 1.0, 1.8, and 2.5 cm at isocenter in the edges of the 2.5 and 5 cm treatment field., Results: The upgrade of CheckTomo was tested on 30 patient treatments planned with dynamic jaws. The gamma pass rate averaged over 10 abdomen plans was 95.9%, with tolerances of 3 mm/3%. For 10 head and neck plans, the mean pass rate was 95.9% for tolerances of 4 mm/4%. Finally, misplacement and overdosage errors were simulated. In each tested cases, the 2 mm/3% gamma pass rate fell below 95% when a 4 mm shift or 3% dose difference was applied., Conclusions: These results are equivalent to what CheckTomo achieves in static jaws cases. So, in terms of dose calculation accuracy and errors detection, the upgraded version of CheckTomo is as reliable for dynamic jaws plans as the former release was for static cases., (© 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Purpose: The Leksell Gamma Knife (LGK) Icon has been recently introduced to provide Gamma Knife technology with frameless stereotactic treatments which use an additional cone-beam CT (CBCT) imaging system and a motion tracking system (IFMM, Intra-Fraction Motion Management). The system was commissioned for the treatment unit itself as well as the imaging system., Methods: The LGK Icon was calibrated using an A1SL ionization chamber. EBT3 radiochromic films were employed to independently check the machine calibration, to measure the relative output factors (ROFs) and to collect dose distributions. Coincidence between CBCT isocenter and radiological focus was evaluated by means of EBT3 films. CBCT image quality was investigated in terms of spatial resolution, contrast-to-noise ratio (CNR), and uniformity for the two presets available (low dose and high dose). Computed Tomography Dose Index (CTDI) was also measured for both presets., Results: The absolute dose rate of the LGK Icon was 3.86 ± 0.09 Gy/min. This result was confirmed by EBT3 readings. ROF were found to be 0.887 ± 0.035 and 0.797 ± 0.032 for the 8 mm and 4 mm collimators, respectively, which are within 2% of the Monte Carlo-derived ROF values. Excellent agreement was found between calculated and measured dose distribution with the gamma pass rate >95% of points for the nine dose distributions analyzed with 3%/1 mm criteria. CBCT isocenter was found to be within 0.2 mm with respect to radiological focus. Image quality parameters were found to be well within the manufacturer's specifications with the high-dose preset being superior in terms of CNR and uniformity. CTDI values were 2.41 mGy and 6.32 mGy, i.e. -3.6% and 0.3% different from the nominal values for the low-dose and high-dose presets, respectively., Conclusions: The LGK Icon was successfully commissioned for clinical use. The use of the EBT3 to characterize the treatment unit was demonstrated to be feasible. The CBCT imaging system operates well within the manufacturer's specifications and provides good geometrical accuracy., (© 2016 American Association of Physicists in Medicine.)

The study was to describe and to compare the performance of 3D and 4D CBCT imaging modalities by measuring and analyzing the delivered dose and the image quality. The 3D (Chest) and 4D (Symmetry) CBCT Elekta XVI lung IGRT protocols were analyzed. Dose profiles were measured with TLDs inside a dedicated phantom. The dosimetric indicator cone-beam dose index (CBDI) was evaluated. The image quality analysis was performed by assessing the contrast transfer function (CTF), the noise power spectrum (NPS) and the noise-equivalent quanta (NEQ). Artifacts were also evaluated by simulating irregular breathing variations. The two imaging modalities showed different dose distributions within the phantom. At the center, the 3D CBCT delivered twice the dose of the 4D CBCT. The CTF was strongly reduced by motion compared to static conditions, resulting in a CTF reduction of 85% for the 3D CBCT and 65% for the 4D CBCT. The amplitude of the NPS was two times higher for the 4D CBCT than for the 3D CBCT. In the presence of motion, the NEQ of the 4D CBCT was 50% higher than the 3D CBCT. In the presence of breathing irregularities, the 4D CBCT protocol was mainly affected by view-aliasing artifacts, which were typically cone-beam artifacts, while the 3D CBCT protocol was mainly affected by duplication artifacts. The results showed that the 4D CBCT ensures a reasonable dose and better image quality when mov-ing targets are involved compared to 3D CBCT. Therefore, 4D CBCT is a reliable imaging modality for lung free-breathing radiation therapy., (© 2016 The Authors.)

We report the first known instance of the clinical use of 99mTc-mebrofenin hepatobiliary scintigraphy (HBS) for the optimization of radiotherapy treatment planning and for the follow-up of acute toxicity in a patient undergoing stereotactic body radiation therapy for hepatocellular carcinoma. In our experience, HBS allowed the identification and the sparing of more functioning liver areas, thus potentially reducing the risk of radiation-induced liver toxicity.

We present an unusual case of suicide by intraperitoneal injection of pentobarbital, an overdose of zolpidem and the intake of diazepam, ethanol and other psychoactive substances. The autopsy and specimen collection were conducted in a 10 to 18 h postmortem interval. The toxicological analysis revealed a significantly higher pentobarbital concentration in femoral blood compared to cardiac blood (36 vs. 15 mg/L). On the contrary, zolpidem and diazepam concentrations in cardiac blood (2700 and 590 µg/L) were found to be significantly higher than in femoral blood (1500 and 230 µg/L). These findings point to a postmortem redistribution with a distinct gradient from areas of high drug concentrations in the gastrointestinal tract (zolpidem and diazepam) and the injection site (pentobarbital) to peripheral tissue. Ethanol concentration was 0.95 ‰ which amplified the CNS depression. The choice of this unusual suicide method was associated with the deceased's former job as a veterinarian's assistant. In veterinary medicine, the intraperitoneal injection of a lethal dose of pentobarbital is quite commonly performed to euthanise small animals. Intraperitoneal injection is rare as route of administration in humans.

Multi-criteria optimization provides decision makers with a range of clinical choices through Pareto plans that can be explored during real time navigation and then converted into deliverable plans. Our study shows that dosimetric differences can arise between the two steps, which could compromise the clinical choices made during navigation., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: To investigate the impact of Toshiba phase- and amplitude-sorting algorithms on the margin strategies for free-breathing lung radiotherapy treatments in the presence of breathing variations., Material and Methods: 4D CT of a sphere inside a dynamic thorax phantom was acquired. The 4D CT was reconstructed according to the phase- and amplitude-sorting algorithms. The phantom was moved by reproducing amplitude, frequency, and a mix of amplitude and frequency variations. Artefact analysis was performed for Mid-Ventilation and ITV-based strategies on the images reconstructed by phase- and amplitude-sorting algorithms. The target volume deviation was assessed by comparing the target volume acquired during irregular motion to the volume acquired during regular motion., Results: The amplitude-sorting algorithm shows reduced artefacts for only amplitude variations while the phase-sorting algorithm for only frequency variations. For amplitude and frequency variations, both algorithms perform similarly. Most of the artefacts are blurring and incomplete structures. We found larger artefacts and volume differences for the Mid-Ventilation with respect to the ITV strategy, resulting in a higher relative difference of the surface distortion value which ranges between maximum 14.6% and minimum 4.1%., Conclusions: The amplitude- is superior to the phase-sorting algorithm in the reduction of motion artefacts for amplitude variations while phase-sorting for frequency variations. A proper choice of 4D CT sorting algorithm is important in order to reduce motion artefacts, especially if Mid-Ventilation strategy is used., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Re-irradiation is frequently performed in radiotherapy (RT) departments. We present an optimization methodology that takes the previous irradiation into account. A 68-year-old female patient suffering from rectal adenocarcinoma, who had previously undergone RT for metastases to the right iliac bone, presented with a recurrence of metastasis to the L5 and the left sacroiliac joint. Re-irradiation was performed using volumetric modulated arc therapy (VMAT). We proceeded to a registration of the previous RT planning CT and RT doses to the new planning CT. Virtual volumes corresponding to the intersection of the small bowel (SB) and each isodose structure were created. We calculated the maximal dose (D max ) that each virtual structure could receive and considered them as constraints. We called this technique modified VMAT. We compared this technique with a standard VMAT plan and a three-dimensional RT plan. Using the modified VMAT technique, a total dose of 20 Gy in five fractions of 4 Gy was delivered to the planning target volume without any acute toxicity. A composite dosimetry was realized with each technique to compare the dose given to the already irradiated SB. We calculated the D max received by the already irradiated SB in equivalent dose of 2 Gy fractions. The Dmax was 46.8, 60 and 52 Gy for modified VMAT, standard VMAT and three-dimensional RT, respectively. Dose deformation was used to create new constraint structures to optimize the dose delivered to surrounding tissues. This methodology is readily feasible in clinical routine to optimize the re-irradiation process.

Background and Purpose: Compensation for respiratory motion is needed while administering radiotherapy (RT) to tumors that are moving with respiration to reduce the amount of irradiated normal tissues and potentially decrease radiation-induced collateral damages. The purpose of this study was to test a new ventilation system designed to induce apnea-like suppression of respiratory motion and allow long enough breath hold durations to deliver complex RT., Material and Methods: The High Frequency Percussive Ventilation system was initially tested in a series of 10 volunteers and found to be well tolerated, allowing a median breath hold duration of 11.6 min (range 3.9-16.5 min). An evaluation of this system was subsequently performed in 4 patients eligible for adjuvant breast 3D conformal RT, for lung stereotactic body RT (SBRT), lung volumetric modulated arc therapy (VMAT), and VMAT for palliative pleural metastases., Results: When compared to free breathing (FB) and maximal inspiration (MI) gating, this Percussion Assisted RT (PART) offered favorable dose distribution profiles in 3 out of the 4 patients tested. PART was applied in these 3 patients with good tolerance, without breaks during the "beam on time period" throughout the overall courses of RT. The mean duration of the apnea-like breath hold that was necessary for delivering all the RT fractions was 7.61 min (SD=2.3)., Conclusions: This first clinical implementation of PART was found to be feasible, tolerable and offers new opportunities in the field of RT for suppressing respiratory motion., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Aims and Background: The standard treatment of anal canal cancer (ACC) is combined chemotherapy and radiation therapy (RT), which is complex because of the shape of the target volumes and the need to minimize the irradiation of normal pelvic structures. In this study we compared the dosimetric results of helical tomotherapy (HT) plans with traditional 3D conformal RT (3DRT) plans for the treatment of ACC., Methods and Study Design: Twelve patients (median age 57 years, range 38-83; F/M 8/4) treated with HT and concurrent chemotherapy for locally advanced ACC were selected. All had histologically confirmed squamous-cell carcinoma. A clinical target volume including the tumor and pelvic and inguinal lymph nodes was treated with HT to a total dose of 36 Gy in 1.8-Gy daily fractions. Then a sequential boost of 23.4 Gy in 1.8-Gy daily fractions (total dose 59.4 Gy) was delivered to the tumor and involved nodes. For all 12 patients, 3DRT plans were generated for comparison. Treatment plans were evaluated by means of standard dose-volume histograms. Dose coverage of the planning target volumes (PTVs), homogeneity index (HI), and mean doses to organs at risk (OARs) were compared., Results: The coverage of PTV was comparable between the two treatment plans. HI was better in the HT vs. 3DRT plans (1.25 and 3.57, respectively; p&lt;0.0001). HT plans resulted in better sparing of OARs (p&lt;0.0001)., Conclusions: HT showed superior target dose conformality and significant sparing of pelvic structures compared with 3DRT. Further investigation should determine if these dosimetric improvements will improve clinical outcomes regarding locoregional control, survival, and treatment-related acute and late morbidity.

The Hi·Art II Helical TomoTherapy (HT) unit is equipped with a built-in onboard MVCT detector used for patient imaging and beam monitoring. Our aim was to study the detector stability for treatment beam measurements. We studied the MVCT detector response with the 6 MV photon beam over time, throughout short-term (during an irradiation) and long-term (two times 50 days) periods. Our results show a coefficient of variation ≤ 1% for detector chambers inside the beam (excluding beam gradients) for short- and long-term response of the MVCT detector. Larger variations were observed in beam gradients and an influence of the X-ray target where degradation was found. The results assume that an 'air scan' procedure is performed daily to recalibrate the detector with the imaging beam. On short term, the detector response stability is comparable to other devices. Long-term measure- ments during two 50-day periods show a good reproducibility.

Purpose: Late toxicities such as second cancer induction become more important as treatment outcome improves. Often the dose distribution calculated with a commercial treatment planning system (TPS) is used to estimate radiation carcinogenesis for the radiotherapy patient. However, for locations beyond the treatment field borders, the accuracy is not well known. The aim of this study was to perform detailed out-of-field-measurements for a typical radiotherapy treatment plan administered with a Cyberknife and a Tomotherapy machine and to compare the measurements to the predictions of the TPS., Materials and Methods: Individually calibrated thermoluminescent dosimeters were used to measure absorbed dose in an anthropomorphic phantom at 184 locations. The measured dose distributions from 6 MV intensity-modulated treatment beams for CyberKnife and TomoTherapy machines were compared to the dose calculations from the TPS., Results: The TPS are underestimating the dose far away from the target volume. Quantitatively the Cyberknife underestimates the dose at 40 cm from the PTV border by a factor of 60, the Tomotherapy TPS by a factor of two. If a 50% dose uncertainty is accepted, the Cyberknife TPS can predict doses down to approximately 10 mGy/treatment Gy, the Tomotherapy-TPS down to 0.75 mGy/treatment Gy. The Cyberknife TPS can then be used up to 10 cm from the PTV border the Tomotherapy up to 35 cm., Conclusions: We determined that the Cyberknife and Tomotherapy TPS underestimate substantially the doses far away from the treated volume. It is recommended not to use out-of-field doses from the Cyberknife TPS for applications like modeling of second cancer induction. The Tomotherapy TPS can be used up to 35 cm from the PTV border (for a 390 cm(3) large PTV)., (Copyright © 2013. Published by Elsevier GmbH.)

The comparison of radiotherapy techniques regarding secondary cancer risk has yielded contradictory results possibly stemming from the many different approaches used to estimate risk. The purpose of this study was to make a comprehensive evaluation of different available risk models applied to detailed whole-body dose distributions computed by Monte Carlo for various breast radiotherapy techniques including conventional open tangents, 3D conformal wedged tangents and hybrid intensity modulated radiation therapy (IMRT). First, organ-specific linear risk models developed by the International Commission on Radiological Protection (ICRP) and the Biological Effects of Ionizing Radiation (BEIR) VII committee were applied to mean doses for remote organs only and all solid organs. Then, different general non-linear risk models were applied to the whole body dose distribution. Finally, organ-specific non-linear risk models for the lung and breast were used to assess the secondary cancer risk for these two specific organs. A total of 32 different calculated absolute risks resulted in a broad range of values (between 0.1% and 48.5%) underlying the large uncertainties in absolute risk calculation. The ratio of risk between two techniques has often been proposed as a more robust assessment of risk than the absolute risk. We found that the ratio of risk between two techniques could also vary substantially considering the different approaches to risk estimation. Sometimes the ratio of risk between two techniques would range between values smaller and larger than one, which then translates into inconsistent results on the potential higher risk of one technique compared to another. We found however that the hybrid IMRT technique resulted in a systematic reduction of risk compared to the other techniques investigated even though the magnitude of this reduction varied substantially with the different approaches investigated. Based on the epidemiological data available, a reasonable approach to risk estimation would be to use organ-specific non-linear risk models applied to the dose distributions of organs within or near the treatment fields (lungs and contralateral breast in the case of breast radiotherapy) as the majority of radiation-induced secondary cancers are found in the beam-bordering regions.

Background and Purpose: Intensity-modulated radiotherapy (IMRT) credentialing for a EORTC study was performed using an anthropomorphic head phantom from the Radiological Physics Center (RPC; RPC(PH)). Institutions were retrospectively requested to irradiate their institutional phantom (INST(PH)) using the same treatment plan in the framework of a Virtual Phantom Project (VPP) for IMRT credentialing., Materials and Methods: CT data set of the institutional phantom and measured 2D dose matrices were requested from centers and sent to a dedicated secure EORTC uploader. Data from the RPC(PH) and INST(PH) were thereafter centrally analyzed and inter-compared by the QA team using commercially available software (RIT; ver.5.2; Colorado Springs, USA)., Results: Eighteen institutions participated to the VPP. The measurements of 6 (33%) institutions could not be analyzed centrally. All other centers passed both the VPP and the RPC ±7%/4 mm credentialing criteria. At the 5%/5 mm gamma criteria (90% of pixels passing), 11(92%) as compared to 12 (100%) centers pass the credentialing process with RPC(PH) and INST(PH) (p = 0.29), respectively. The corresponding pass rate for the 3%/3 mm gamma criteria (90% of pixels passing) was 2 (17%) and 9 (75%; p = 0.01), respectively., Conclusions: IMRT dosimetry gamma evaluations in a single plane for a H&N prospective trial using the INST(PH) measurements showed agreement at the gamma index criteria of ±5%/5 mm (90% of pixels passing) for a small number of VPP measurements. Using more stringent, criteria, the RPC(PH) and INST(PH) comparison showed disagreement. More data is warranted and urgently required within the framework of prospective studies.

Background: Whole pelvis intensity modulated radiotherapy (IMRT) is increasingly being used to treat cervical cancer aiming to reduce side effects. Encouraged by this, some groups have proposed the use of simultaneous integrated boost (SIB) to target the tumor, either to get a higher tumoricidal effect or to replace brachytherapy. Nevertheless, physiological organ movement and rapid tumor regression throughout treatment might substantially reduce any benefit of this approach., Purpose: To evaluate the clinical target volume - simultaneous integrated boost (CTV-SIB) regression and motion during chemo-radiotherapy (CRT) for cervical cancer, and to monitor treatment progress dosimetrically and volumetrically to ensure treatment goals are met., Methods and Materials: Ten patients treated with standard doses of CRT and brachytherapy were retrospectively re-planned using a helical Tomotherapy - SIB technique for the hypothetical scenario of this feasibility study. Target and organs at risk (OAR) were contoured on deformable fused planning-computed tomography and megavoltage computed tomography images. The CTV-SIB volume regression was determined. The center of mass (CM) was used to evaluate the degree of motion. The Dice's similarity coefficient (DSC) was used to assess the spatial overlap of CTV-SIBs between scans. A cumulative dose-volume histogram modeled estimated delivered doses., Results: The CTV-SIB relative reduction was between 31 and 70%. The mean maximum CM change was 12.5, 9, and 3 mm in the superior-inferior, antero-posterior, and right-left dimensions, respectively. The CTV-SIB-DSC approached 1 in the first week of treatment, indicating almost perfect overlap. CTV-SIB-DSC regressed linearly during therapy, and by the end of treatment was 0.5, indicating 50% discordance. Two patients received less than 95% of the prescribed dose. Much higher doses to the OAR were observed. A multiple regression analysis showed a significant interaction between CTV-SIB reduction and OAR dose increase., Conclusions: The CTV-SIB had important regression and motion during CRT, receiving lower therapeutic doses than expected. The OAR had unpredictable shifts and received higher doses. The use of SIB without frequent adaptation of the treatment plan exposes cervical cancer patients to an unpredictable risk of under-dosing the target and/or overdosing adjacent critical structures. In that scenario, brachytherapy continues to be the gold standard approach.

Background and Purpose: To make a comprehensive evaluation of organ-specific out-of-field doses using Monte Carlo (MC) simulations for different breast cancer irradiation techniques and to compare results with a commercial treatment planning system (TPS)., Materials and Methods: Three breast radiotherapy techniques using 6MV tangential photon beams were compared: (a) 2DRT (open rectangular fields), (b) 3DCRT (conformal wedged fields), and (c) hybrid IMRT (open conformal+modulated fields). Over 35 organs were contoured in a whole-body CT scan and organ-specific dose distributions were determined with MC and the TPS., Results: Large differences in out-of-field doses were observed between MC and TPS calculations, even for organs close to the target volume such as the heart, the lungs and the contralateral breast (up to 70% difference). MC simulations showed that a large fraction of the out-of-field dose comes from the out-of-field head scatter fluence (>40%) which is not adequately modeled by the TPS. Based on MC simulations, the 3DCRT technique using external wedges yielded significantly higher doses (up to a factor 4-5 in the pelvis) than the 2DRT and the hybrid IMRT techniques which yielded similar out-of-field doses., Conclusions: In sharp contrast to popular belief, the IMRT technique investigated here does not increase the out-of-field dose compared to conventional techniques and may offer the most optimal plan. The 3DCRT technique with external wedges yields the largest out-of-field doses. For accurate out-of-field dose assessment, a commercial TPS should not be used, even for organs near the target volume (contralateral breast, lungs, heart)., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

The quantity of interest for high-energy photon beam therapy recommended by most dosimetric protocols is the absorbed dose to water. Thus, ionization chambers are calibrated in absorbed dose to water, which is the same quantity as what is calculated by most treatment planning systems (TPS). However, when measurements are performed in a low-density medium, the presence of the ionization chamber generates a perturbation at the level of the secondary particle range. Therefore, the measured quantity is close to the absorbed dose to a volume of water equivalent to the chamber volume. This quantity is not equivalent to the dose calculated by a TPS, which is the absorbed dose to an infinitesimally small volume of water. This phenomenon can lead to an overestimation of the absorbed dose measured with an ionization chamber of up to 40% in extreme cases. In this paper, we propose a method to calculate correction factors based on the Monte Carlo simulations. These correction factors are obtained by the ratio of the absorbed dose to water in a low-density medium □D(w,Q,V1)(low) averaged over a scoring volume V₁ for a geometry where V₁ is filled with the low-density medium and the absorbed dose to water □D(w,QV2)(low) averaged over a volume V₂ for a geometry where V₂ is filled with water. In the Monte Carlo simulations, □D(w,QV2)(low) is obtained by replacing the volume of the ionization chamber by an equivalent volume of water, according to the definition of the absorbed dose to water. The method is validated in two different configurations which allowed us to study the behavior of this correction factor as a function of depth in phantom, photon beam energy, phantom density and field size.

3D dose reconstruction is a verification of the delivered absorbed dose. Our aim was to describe and evaluate a 3D dose reconstruction method applied to phantoms in the context of narrow beams. A solid water phantom and a phantom containing a bone-equivalent material were irradiated on a 6 MV linac. The transmitted dose was measured by using one array of a 2D ion chamber detector. The dose reconstruction was obtained by an iterative algorithm. A phantom set-up error and organ interfraction motion were simulated to test the algorithm sensitivity. In all configurations convergence was obtained within three iterations. A local reconstructed dose agreement of at least 3% / 3mm with respect to the planned dose was obtained, except in a few points of the penumbra. The reconstructed primary fluences were consistent with the planned ones, which validates the whole reconstruction process. The results validate our method in a simple geometry and for narrow beams. The method is sensitive to a set-up error of a heterogeneous phantom and interfraction heterogeneous organ motion., (Copyright © 2011. Published by Elsevier GmbH.)

Second cancer risk assessment for radiotherapy is controversial due to the large uncertainties of the dose-response relationship. This could be improved by a better assessment of the peripheral doses to healthy organs in future epidemiological studies. In this framework, we developed a simple Monte Carlo (MC) model of the Siemens Primus 6 MV linac for both open and wedged fields that we then validated with dose profiles measured in a water tank up to 30 cm from the central axis. The differences between the measured and calculated doses were comparable to other more complex MC models and never exceeded 50%. We then compared our simple MC model with the peripheral dose profiles of five different linacs with different collimation systems. We found that the peripheral dose between two linacs could differ up to a factor of 9 for small fields (5 × 5 cm2) and up to a factor of 10 for wedged fields. Considering that an uncertainty of 50% in dose estimation could be acceptable in the context of risk assessment, the MC model can be used as a generic model for large open fields (≥10 × 10 cm2) only. The uncertainties in peripheral doses should be considered in future epidemiological studies when designing the width of the dose bins to stratify the risk as a function of the dose.

Background: Surgery of radiation-induced cataracts in children with retinoblastoma (RB) is a challenge as early intervention is weighted against the need to delay surgery until complete tumour control is obtained. This study analyses the safety and functional results of such surgery., Methods: In a retrospective, non-comparative, consecutive case series, we reviewed medical records of RB patients ≤ 14 y of age who underwent either external beam radiotherapy or plaque treatment and were operated for radiation-induced cataract between 1985 and 2008., Results: In total, 21 eyes of 20 RB patients were included and 18 out of the 21 eyes had Reese-Ellsworth stage V or ABC classification group D/E RB. Median interval between last treatment for RB and cataract surgery was 21.5 months, range 3-164 months. Phacoaspiration was performed in 13 eyes (61%), extra-capsular cataract extraction in 8 (39%) and intraocular lens implantation in 19 eyes (90%). The majority of cases, 11/21 (52%), underwent posterior capsulorhexis or capsulotomy and 6/21 (28%) an anterior vitrectomy. Postoperative visual acuity was ≥ 20/200 in 13 eyes and < 20/200 in 5 eyes. Intraocular tumour recurrence was noted in three eyes. Mean postoperative follow up was 90 months ± 69 months., Conclusions: Modern cataract surgery, including clear cornea approach, lens aspiration with posterior capsulotomy, anterior vitrectomy and IOL implantation is a safe procedure for radiation-induced cataract as long as RB is controlled. The visual prognosis is limited by initial tumour involvement of the macula and by corneal complications of radiotherapy. We recommend a minimal interval of 9 months between completion of treatment of retinoblastoma and cataract surgery.

Purpose: A 2-year-old boy with syndromic bilateral retinoblastoma resulting from a (del(13)(q12.3q14.3)) developed a recurrent tumor measuring 2.3 X 2.3 mm at the ora serrata 15 months following last treatment., Methods: Ultrasound biomicroscopy (UBM) revealed a mass invading the ciliary body 6.6 mm in diameter associated with a localized supraciliary effusion., Results: Complete tumor regression was achieved 1 month after brachytherapy with a (106)Ruthenium plaque. There was no recurrence at 16 months., Conclusion: This is the first clinical demonstration of supraciliary effusion in recurrent retinoblastoma. Brachytherapy appears to be effective in the treatment of this type of recurrence.

Purpose: A helical tomotherapy accelerator presents a dosimetric challenge because, to this day, there is no internationally accepted protocol for the determination of the absolute dose. Because of this reality, we investigated the different alternatives for characterizing and measuring the absolute dose of such an accelerator. We tested several dosimetric techniques with various metrological traceabilities as well as using a number of phantoms in static and helical modes., Methods: Firstly, the relationship between the reading of ionization chambers and the absorbed dose is dependent on the beam quality value of the photon beam. For high energy photons, the beam quality is specified by the tissue phantom ratio (TPR20,10) and it is therefore necessary to know the TPR20,10 to calculate the dose delivered by a given accelerator. This parameter is obtained through the ratio of the absorbed dose at 20 and 10 cm depths in water and was measured in the particular conditions of the tomotherapy accelerator. Afterward, measurements were performed using the ionization chamber (model A1SL) delivered as a reference instrument by the vendor. This chamber is traceable in absorbed dose to water in a Co-60 beam to a water calorimeter of the American metrology institute (NIST). Similarly, in Switzerland, each radiotherapy department is directly traceable to the Swiss metrology institute (METAS) in absorbed dose to water based on a water calorimeter. For our research, this traceability was obtained by using an ionization chamber traceable to METAS (model NE 2611A), which is the secondary standard of our institute. Furthermore, in order to have another fully independent measurement method, we determined the dose using alanine dosimeters provided by and traceable to the British metrology institute (NPL); they are calibrated in absorbed dose to water using a graphite calorimeter. And finally, we wanted to take into account the type of chamber routinely used in clinical practice and therefore measured the dose using a Farmer-type instrument (model NE 2571) as well., Results: We found the tomotherapy TPR20,10 value to be around 0.629, which is close to a 4 MV conventional linear accelerator value. During static irradiation, the secondary standard and the alanine dosimeters were compatible within 0.5%. The A1SL relative deviation to the secondary standard was 1.2% and the NE2571 relative deviation to the secondary standard was -1.7%. The measurement in dynamic helical mode found the different dosimeters compatible within 1.4% and the alanine dosimeters and the secondary standard were even found under 0.2%., Conclusions: We found that the different methods are all within uncertainties as well as globally coherent, and the specific limitations of the various dosimeters are discussed in order to help the medical physicist design an independent reference system. We demonstrated that, taking into account the particular reference conditions, one can use an ionization chamber calibrated for conventional linear accelerators to assert the absolute dose delivered by a tomotherapy accelerator.

Intensity-modulated radiotherapy (IMRT) treatment plan verification by comparison with measured data requires having access to the linear accelerator and is time consuming. In this paper, we propose a method for monitor unit (MU) calculation and plan comparison for step and shoot IMRT based on the Monte Carlo code EGSnrc/BEAMnrc. The beamlets of an IMRT treatment plan are individually simulated using Monte Carlo and converted into absorbed dose to water per MU. The dose of the whole treatment can be expressed through a linear matrix equation of the MU and dose per MU of every beamlet. Due to the positivity of the absorbed dose and MU values, this equation is solved for the MU values using a non-negative least-squares fit optimization algorithm (NNLS). The Monte Carlo plan is formed by multiplying the Monte Carlo absorbed dose to water per MU with the Monte Carlo/NNLS MU. Several treatment plan localizations calculated with a commercial treatment planning system (TPS) are compared with the proposed method for validation. The Monte Carlo/NNLS MUs are close to the ones calculated by the TPS and lead to a treatment dose distribution which is clinically equivalent to the one calculated by the TPS. This procedure can be used as an IMRT QA and further development could allow this technique to be used for other radiotherapy techniques like tomotherapy or volumetric modulated arc therapy.

Background and Purpose: To compare the delineations and interpretations of target volumes by physicians in different radio-oncology centers., Materials and Methods: Eleven Swiss radio-oncology centers delineated volumes according to ICRU 50 recommendations for one prostate and one head and neck case. In order to evaluate the consistency of the volume delineations, the following parameters were determined: 1) the target volumes (GTV, CTV and manually expanded PTV) and their extensions in the three main axes and 2) the correlation of the volume delineated by each pair of centers using the ratio of the intersection to the union (called proximity index)., Results: The delineated prostate volume was 105+/-55 cm(3) for the CTV and 218+/-44 cm(3) for the PTV. The delineated head and neck volume was 46+/-15 cm(3) for the GTV, 327+/-154 cm(3) for the CTV and 528+/-106 cm(3) for the PTV. The mean proximity index for the prostate case was 0.50+/-0.13 for the CTV and 0.57+/-0.11 for the PTV. The proximity index for the head and neck case was 0.45+/-0.09 for the GTV, 0.42+/-0.13 for the CTV and 0.59+/-0.06 for the PTV., Conclusions: Large discrepancies between all the delineated target volumes were observed. There was an inverse relationship between the CTV volume and the margin between CTV and PTV, leading to less discrepancies in the PTV than is the CTV delineations. There was more spread in the sagittal and frontal planes due to CT pixel anisotropy, which suggests that radiation oncologists should delineate the target volumes not only in the transverse plane, but also in the sagittal and frontal planes to improve the delineation by allowing a consistency check.

Radiotherapy is widely used to treat human cancer. Patients locally recurring after radiotherapy, however, have increased risk of metastatic progression and poor prognosis. The clinical management of postradiation recurrences remains an unresolved issue. Tumors growing in preirradiated tissues have an increased fraction of hypoxic cells and are more metastatic, a condition known as tumor bed effect. The transcription factor hypoxia inducible factor (HIF)-1 promotes invasion and metastasis of hypoxic tumors, but its role in the tumor bed effect has not been reported. Here, we show that tumor cells derived from SCCVII and HCT116 tumors growing in a preirradiated bed, or selected in vitro through repeated cycles of severe hypoxia, retain invasive and metastatic capacities when returned to normoxia. HIF activity, although facilitating metastatic spreading of tumors growing in a preirradiated bed, is not essential. Through gene expression profiling and gain- and loss-of-function experiments, we identified the matricellular protein CYR61 and alphaVbeta5 integrin as proteins cooperating to mediate these effects. The anti-alphaV integrin monoclonal antibody 17E6 and the small molecular alphaVbeta3/alphaVbeta5 integrin inhibitor EMD121974 suppressed invasion and metastasis induced by CYR61 and attenuated metastasis of tumors growing within a preirradiated field. These results represent a conceptual advance to the understanding of the tumor bed effect and identify CYR61 and alphaVbeta5 integrin as proteins that cooperate to mediate metastasis. They also identify alphaV integrin inhibition as a potential therapeutic approach for preventing metastasis in patients at risk for postradiation recurrences.