Low-Dose Radiation Therapy Impacts Microglial Inflammatory Response without Modulating Amyloid Load in Female TgF344-AD Rats.

Background: Low-dose radiation therapy (LD-RT) has demonstrated in preclinical and clinical studies interesting properties in the perspective of targeting Alzheimer's disease (AD), including anti-amyloid and anti-inflammatory effects. Nevertheless, studies were highly heterogenous with respect to total doses, fractionation protocols, sex, age at the time of treatment and delay post treatment. Recently, we demonstrated that LD-RT reduced amyloid peptides and inflammatory markers in 9-month-old TgF344-AD (TgAD) males. Objective: As multiple studies demonstrated a sex effect in AD, we wanted to validate that LD-RT benefits are also observed in TgAD females analyzed at the same age. Methods: Females were bilaterally treated with 2 Gy×5 daily fractions, 2 Gy×5 weekly fractions, or 10 fractions of 1 Gy delivered twice a week. The effect of each treatment on amyloid load and inflammation was evaluated using immunohistology and biochemistry. Results: A daily treatment did not affect amyloid and reduced only microglial-mediated inflammation markers, the opposite of the results obtained in our previous male study. Moreover, altered fractionations (2 Gy×5 weekly fractions or 10 fractions of 1 Gy delivered twice a week) did not influence the amyloid load or neuroinflammatory response in females. Conclusions: A daily treatment consequently appears to be the most efficient for AD. This study also shows that the anti-amyloid and anti-inflammatory response to LD-RT are, at least partly, two distinct mechanisms. It also emphasizes the necessity to assess the sex impact when evaluating responses in ongoing pilot clinical trials testing LD-RT against AD.

Elective Nodal Irradiation for Oligorecurrent Nodal Prostate Cancer: Interobserver Variability in the PEACE V-STORM Randomized Phase 2 Trial.

Purpose: Consistency in delineation of pelvic lymph node regions for prostate cancer elective nodal radiation therapy is still challenging despite current guidelines. The aim of this study was to evaluate the interobserver variability in elective lymph node delineation in the PEACE V - STORM randomized phase 2 trial for oligorecurrent nodal prostate cancer. Methods and Materials: Twenty-three centers were asked to delineate the elective pelvic nodal clinical target volume (CTV) of a postoperative oligorecurrent nodal prostate cancer benchmark case using a modified Radiation Therapy Oncology Group (RTOG) 2009 template (upper limit at the L4/L5 interspace). Overall, intersection and overflow volumes, Dice coefficient, Hausdorff distance, and count maps merged with computed tomography images were analyzed. Results: The mean volume including the 23 nodal CTVs was 430.4 ± 64.1 cm3, larger than the modified RTOG 2009 CTV reference volume (386.1 cm3). The intersection common volume between the modified reference RTOG 2009 and the 23 nodal CTVs was estimated at 83.9%, whereas the overflow volume was 23.4%, mainly located at the level of the presacral and the upper limit of the L4/L5 interspace. The mean Dice coefficient was 0.79 ± 0.02, whereas the mean Hausdorff distance was 27 ± 4.4 mm. Conclusions: In salvage radiation therapy treatment of oligorecurrent nodal prostate cancer, variations in elective lymph node volume delineation were mainly observed in the presacral and common iliac areas. Routine implementation and diffusion of available contouring guidelines together with a constant evaluation and evidence-based updating are expected to further decrease the existing variability in pelvic node contouring.

Low-dose brain irradiation normalizes TSPO and CLUSTERIN levels and promotes the non-amyloidogenic pathway in pre-symptomatic TgF344-AD rats.

Preclinical studies have recently evaluated the impact of low-dose brain radiation therapy (LD-RT) in animal models of Alzheimer's disease (AD) showing anti-amyloid and anti-inflammatory effects of this treatment. Its effectiveness varied, however, depending on the LD-RT protocol used and the stage when the treatment was applied. In this study, we aimed to evaluate the therapeutic potential of 10 Gy delivered in five daily fractions of 2 Gy (a protocol previously shown to induce an improvement of cognitive performances) in 9-month-old TgF344-AD rats, modeling at a pre-symptomatic stage of the disease. We showed that at an early stage, LD-RT was able to lower levels of the 18-kDa translocator protein (TSPO)-mediated neuroinflammation to normal ranges in addition to the secreted CLUSTERIN, another inflammatory protein also involved in Aß aggregation. In addition, we demonstrated that LD-RT reduces all amyloid forms (~ - 60 to - 80%, P < 0.01; soluble and aggregated forms of Aß40, Aß42, and Aßoligomers). Interestingly, we showed for the first time that sAPPα levels were improved by the treatment, showing a higher activation of the non-amyloidogenic pathway, that could favor neuronal survival. The current evidence confirms the capacity of LD-RT to successfully modulate two pathological hallmarks of AD, namely amyloid and neuroinflammation, when applied before symptoms onset.

Urinary toxicity after salvage re-irradiation for prostate cancer local failure after definitive radiotherapy: a clinical and dosimetric prognostic factors analysis.

Purpose: Predictors of long-term toxicity after prostate cancer re-irradiation are scarce. In this study, we retrospectively assessed the impact of clinical/dosimetric data on late genitourinary (GU) toxicity on fourteen radio-recurrent prostate cancer patients treated with salvage radiotherapy (RT). Material and methods: To identify dose parameters and clinical factors potentially associated to severe long-term GU toxicity, study population was stratified in two groups according to toxicity, including one low-grade group (grade ≤ 2, n = 6) and one high-grade group (grade ≥ 3, n = 8). Dose prescription at primary and salvage-RT in 2 Gy equivalent dose (EQD2Gy) per fraction, treatment techniques, and clinical factors potentially associated to severe GU toxicity were analyzed. Results: At salvage-RT, the median EQD2Gy α/ß = 3 Gy was significantly higher in the high-toxicity group (85 Gy, range, 71-85 Gy) compared to the low-toxicity group (77 Gy, range, 61-85 Gy) (p = 0.01). All patients treated using salvage-RT with a brachytherapy (BT) boost and with a baseline Framingham risk-score of > 20% (n = 8) developed severe GU toxicity, while none of the remaining patients developed a grade 3 or more GU toxicity (p = 0.0003). V70 > 0 and V75 > 0 of the primary treatment were associated with an increased rate of toxicity. Conclusions: Our analysis shows that the delivery of doses up to 75-80 Gy (EQD2Gy, α/ß = 3 Gy) in salvage-RT can be safe in terms of severe GU toxicity avoidance. Furthermore, concomitant cardiovascular comorbidities seem to increase the risk to develop severe GU toxicity.

Oligorecurrent nodal prostate cancer: Radiotherapy quality assurance of the randomized PEACE V-STORM phase II trial.

PURPOSE: Aim of this study is to report the results of the radiotherapy quality assurance program of the PEACE V-STORM randomized phase II trial for pelvic nodal oligorecurrent prostate cancer (PCa). MATERIAL AND METHODS: A benchmark case (BC) consisting of a postoperative case with 2 nodal recurrences was used for both stereotactic body radiotherapy (SBRT, 30 Gy/3 fx) and whole pelvic radiotherapy (WPRT, 45 Gy/25 fx + SIB boost to 65 Gy). RESULTS: BC of 24 centers were analyzed. The overall grading for delineation variation of the 1st BC was rated as 'UV' (Unacceptable Variation) or 'AV' (Acceptable Variation) for 1 and 7 centers for SBRT (33%), and 3 and 8 centers for WPRT (46%), respectively. An inadequate upper limit of the WPRT CTV (n = 2), a missing delineation of the prostate bed (n = 1), and a missing nodal target volume (n = 1 for SBRT and WPRT) constituted the observed 'UV'. With the 2nd BC (n = 11), the overall delineation review showed 2 and 8 'AV' for SBRT and WPRT, respectively, with no 'UV'. For the plan review of the 2nd BC, all treatment plans were per protocol for WPRT. SBRT plans showed variability in dose normalization (Median D90% = 30.1 Gy, range 22.9-33.2 Gy and 30.6 Gy, range 26.8-34.2 Gy for nodes 1 and 2 respectively). CONCLUSIONS: Up to 46% of protocol deviations were observed in delineation of WPRT for nodal oligorecurrent PCa, while dosimetric results of SBRT showed the greatest disparities between centers. Repeated BC resulted in an improved adherence to the protocol, translating in an overall acceptable contouring and planning compliance rate among participating centers.

Combined hyperthermia and radiotherapy for prostate cancer: a systematic review.

Optimization of treatment strategies for prostate cancer patients treated with curative radiation therapy (RT) represents one of the major challenges for the radiation oncologist. Dose escalation or combination of RT with systemic therapies is used to improve tumor control in patients with unfavorable prostate cancer, at the risk of increasing rates and severity of treatment-related toxicities. Elevation of temperature to a supra-physiological level has been shown to both increase tumor oxygenation and reduce DNA repair capabilities. Thus, hyperthermia (HT) combined with RT represents a compelling treatment strategy to improve the therapeutic ratio in prostate cancer patients. The aim of the present systematic review is to report on preclinical and clinical evidence supporting the combination of HT and RT for prostate cancer, discussing future applications and developments of this combined treatment.

Low-Dose Radiation Therapy Reduces Amyloid Load in Young 3xTg-AD Mice.

BACKGROUND: Low-dose radiation therapy (LD-RT) has been shown to decrease amyloidosis or inflammation in systemic diseases and has recently been proposed as possible treatment of Alzheimer's disease (AD). A positive effect of LD-RT on tauopathy, the other marker of AD, has also been suggested. These effects have been shown in preclinical studies, but their mechanisms are still not well understood. OBJECTIVE: This study aimed to evaluate if anti-amyloid and anti-inflammatory effects of LD-RT can be observed at an early stage of the disease. Its impact on tauopathy and behavioral alterations was also investigated. METHODS: The whole brain of 12-month-old 3xTg-AD mice was irradiated with 10 Gy in 5 daily fractions of 2 Gy. Mice underwent behavioral tests before and 8 weeks post treatment. Amyloid load, tauopathy, and neuroinflammation were measured using histology and/or ELISA. RESULTS: Compared with wild-type animals, 3xTg-AD mice showed a moderate amyloid and tau pathology restricted to the hippocampus, a glial reactivity restricted to the proximity of amyloid plaques. LD-RT significantly reduced Aß42 aggregated forms (-71%) in the hippocampus and tended to reduce other forms in the hippocampus and frontal cortex but did not affect tauopathy or cognitive performance. A trend for neuroinflammation markers reduction was also observed. CONCLUSION: When applied at an early stage, LD-RT reduced amyloid load and possibly neuroinflammation markers, with no impact on tauopathy. The long-term persistence of these beneficial effects of LD-RT should be evaluated in future studies.

Prone versus supine free-breathing for right-sided whole breast radiotherapy.

Prone setup has been advocated to improve organ sparing in whole breast radiotherapy without impairing breast coverage. We evaluate the dosimetric advantage of prone setup for the right breast and look for predictors of the gain. Right breast cancer patients treated in 2010-2013 who had a dual supine and prone planning were retrospectively identified. A penalty score was computed from the mean absolute dose deviation to heart, lungs, breasts, and tumor bed for each patient's supine and prone plan. Dosimetric advantage of prone was assessed by the reduction of penalty score from supine to prone. The effect of patients' characteristics on the reduction of penalty was analyzed using robust linear regression. A total of 146 patients with right breast dual plans were identified. Prone compared to supine reduced the penalty score in 119 patients (81.5%). Lung doses were reduced by 70.8%, from 4.8 Gy supine to 1.4 Gy prone. Among patient's characteristics, the only significant predictors were the breast volumes, but no cutoff could identify when prone would be less advantageous than supine. Prone was associated with a dosimetric advantage in most patients. It sets a benchmark of achievable lung dose reduction.Trial registration: ClinicalTrials.gov NCT02237469, HUGProne, September 11, 2014, retrospectively registered.

Bilateral metallic hip implants: Are avoidance sectors necessary for pelvic VMAT treatments?

PURPOSE: Metallic hip implants (MHI) are common in elderly patients. For pelvic cancers radiotherapy, conventional approaches consist of MHI avoidance during treatment planning, which leads, especially in case of bilateral MHI, to a decreased quality or increased complexity of the treatment plan. The aim of this study is to investigate the necessity of using avoidance sectors (AvSe) using a 2-arcs coplanar pelvic volumetric modulated arc-therapy (VMAT) planning. METHODS: We evaluated: (1) The dose calculation error of a static 6MV open beam traversing a MHI; (2) The magnitude of an error's decrease within the planning target volume (PTV) for a 360° VMAT treatment without AvSe as compared to the static open beam; (3) The dosimetric influence of MHI misalignment generated by patient's repositioning rolls during image-guided radiotherapy (IGRT). RESULTS: (1) In the static 6MV beam configuration, for distances between 0.5cm and 6cm from the MHI, the median (maximum, number of points) dose calculation error was -1.55% (-2.5%, 11); (2) Compared to the static open beam, in the 360° VMAT treatment without AvSe a simulated error was decreased by a factor of 4.4/2.4 (median/minimum); (3) MHI anterior-posterior misalignment exceeding 0.6cm, resulted in error at PTV surface of >2%. CONCLUSIONS: A standard 2 coplanar arcs 360° VMAT treatment, with dedicated artifact reduction algorithms applied, decreased the error of static beam traversing MHI, in patients presenting a bilateral MHI and might be used to treat the pelvic region without MHI avoidance.

Treatment by low-dose brain radiation therapy improves memory performances without changes of the amyloid load in the TgF344-AD rat model.

Alzheimer's disease (AD) is a neurodegenerative condition affecting memory performance. This pathology is characterized by intracerebral amyloid plaques and tau tangles coupled with neuroinflammation. During the last century, numerous therapeutic trials unfortunately failed highlighting the need to find new therapeutic approaches. Low-dose brain radiotherapy (LD-RT) showed efficacy to reduce amyloid load and inflammation in patients with peripheral diseases. In this study, the therapeutic potential of 2 LD-RT schedules was tested on the TgF344-AD rat model of AD. Fifteen-month-old rats were irradiated with 5 fractions of 2 Gy delivered either daily or weekly. The daily treatment induced an improvement of memory performance in the Y-maze. In contrast, the weekly treatment increased the microglial reactivity in the hippocampus. A lack of effect of both regimens on amyloid pathology was unexpectedly observed. The positive effect on cognition encourages to further evaluate the LD-RT therapeutic potential and highlights the impact of the design choice of the LD-RT regimen.

Is prone free breathing better than supine deep inspiration breath-hold for left whole-breast radiotherapy? A dosimetric analysis.

PURPOSE: The advantage of prone setup compared with supine for left-breast radiotherapy is controversial. We evaluate the dosimetric gain of prone setup and aim to identify predictors of the gain. METHODS: Left-sided breast cancer patients who had dual computed tomography (CT) planning in prone free breathing (FB) and supine deep inspiration breath-hold (DiBH) were retrospectively identified. Radiation doses to heart, lungs, breasts, and tumor bed were evaluated using the recently developed mean absolute dose deviation (MADD). MADD measures how widely the dose delivered to a structure deviates from a reference dose specified for the structure. A penalty score was computed for every treatment plan as a weighted sum of the MADDs normalized to the breast prescribed dose. Changes in penalty scores when switching from supine to prone were assessed by paired t-tests and by the number of patients with a reduction of the penalty score (i.e., gain). Robust linear regression and fractional polynomials were used to correlate patients' characteristics and their respective penalty scores. RESULTS: Among 116 patients identified with dual CT planning, the prone setup, compared with supine, was associated with a dosimetric gain in 72 (62.1%, 95% CI: 52.6-70.9%). The most significant predictors of a gain with the prone setup were the breast depth prone/supine ratio (>1.6), breast depth difference (>31 mm), prone breast depth (>77 mm), and breast volume (>282 mL). CONCLUSION: Prone compared with supine DiBH was associated with a dosimetric gain in 62.1% of our left-sided breast cancer patients. High pendulousness and moderately large breast predicted for the gain.

Two-Level Factorial Pre-TomoBreast Pilot Study of Tomotherapy and Conventional Radiotherapy in Breast Cancer: Post Hoc Utility of a Mean Absolute Dose Deviation Penalty Score.

BACKGROUND: A 2-level factorial pilot study was conducted in 2007 just before starting a randomized clinical trial comparing tomotherapy and conventional radiotherapy (CR) to reduce cardiac and pulmonary adverse effects in breast cancer, considering tumor laterality (left/right), target volume (with/without nodal irradiation), surgery (tumorectomy/mastectomy), and patient position (prone/supine). The study was revisited using a penalty score based on the recently developed mean absolute dose deviation (MADD). METHODS: Eight patients with a unique combination of laterality, nodal coverage, and surgery underwent dual tomotherapy and CR treatment planning in both prone and supine positions, providing 32 distinct combinations. The penalty score was applied using the weighted sum of the MADDs. The Lenth method for unreplicated 2-level factorial design was used in the analysis. RESULTS: The Lenth analysis identified nodal irradiation as the active main effect penalizing the dosimetry by 1.14 Gy (P = 0.001). Other significant effects were left laterality (0.94 Gy), mastectomy (0.61 Gy), and interactions between left mastectomy (0.89 Gy) and prone mastectomy (0.71 Gy), with P-values between 0.005 and 0.05. Tomotherapy provided a small reduction in penalty (reduction of 0.54 Gy) through interaction with nodal irradiation (P = 0.080). Some effects approached significance with P-values > 0.05 and ≤ 0.10 for interactions of prone × mastectomy × left (0.60 Gy), nodal irradiation × mastectomy (0.59 Gy), and prone × left (0.55 Gy) and the main effect prone (0.52 Gy). CONCLUSIONS: The historical dosimetric analysis previously revealed the feasibility of tomotherapy, but a conclusion could not be made. The MADD-based score is promising, and a new analysis highlights the impact of factors and hierarchy of priorities that need to be addressed if major gains are to be attained.

3D printing for dosimetric optimization and quality assurance in small animal irradiations using megavoltage X-rays.

PURPOSE: New therapeutic options in radiotherapy (RT) are often explored in preclinical in-vivo studies using small animals. We report here on the feasibility of modern megavoltage (MV) linear accelerator (LINAC)-based RT for small animals using easy-to-use consumer 3D printing technology for dosimetric optimization and quality assurance (QA). METHODS: In this study we aimed to deliver 5×2Gy to the half-brain of a rat using a 4MV direct hemi-field X-ray beam. To avoid the beam's build-up in the target and optimize dosimetry, a 1cm thick, customized, 3D-printed bolus was used. A 1:1 scale copy of the rat was 3D printed based on the CT dataset as an end-to-end QA tool. The plan robustness to HU changes was verified. Thermoluminescent dosimeters (TLDs), for both MV irradiations and for kV imaging doses, and a gafchromic film were placed within the phantom for dose delivery verifications. The phantom was designed using a standard treatment planning software, and was irradiated at the LINAC with the target aligned using kV on-board imaging. RESULTS: The plan was robust (dose difference<1% for HU modification from 0 to 250). Film dosimetry showed a good concordance between planned and measured dose, with the steep dose gradient at the edge of the hemi-field properly aligned to spare the contralateral half-brain. In the treated region, the mean TLDs percentage dose differences (±2 SD) were 1.3% (±3.8%) and 0.9% (±1.7%) beneath the bolus. The mean (±2 SD) out-of-field dose measurements was 0.05Gy (±0.02Gy) for an expected dose of 0.04Gy. Imaging doses (2mGy) still spared the contralateral-brain. CONCLUSIONS: Use of consumer 3D-printers enables dosimetry optimization and QA assessment for small animals MV RT in preclinical studies using standard LINACS.

Atlas Sampling for Prone Breast Automatic Segmentation of Organs at Risk: The Importance of Patients' Body Mass Index and Breast Cup Size for an Optimized Contouring of the Heart and the Coronary Vessels.

OBJECTIVE: Delineation of organs at risk is a time-consuming task. This study evaluates the benefits of using single-subject atlas-based automatic segmentation of organs at risk in patients with breast cancer treated in prone position, with 2 different criteria for choosing the atlas subject. Together with laterality (left/right), the criteria used were either (1) breast volume or (2) body mass index and breast cup size. METHODS: An atlas supporting different selection criteria for automatic segmentation was generated from contours drawn by a senior radiation oncologist (RO_A). Atlas organs at risk included heart, left anterior descending artery, and right coronary artery. Manual contours drawn by RO_A and automatic segmentation contours of organs at risk and breast clinical target volume were created for 27 nonatlas patients. A second radiation oncologist (RO_B) manually contoured (M_B) the breast clinical target volume and the heart. Contouring times were recorded and the reliability of the automatic segmentation was assessed in the context of 3-D planning. RESULTS: Accounting for body mass index and breast cup size improved automatic segmentation results compared to breast volume-based sampling, especially for the heart (mean similarity indexes >0.9 for automatic segmentation organs at risk and clinical target volume after RO_A editing). Mean similarity indexes for the left anterior descending artery and the right coronary artery edited by RO_A expanded by 1 cm were ≥0.8. Using automatic segmentation reduced contouring time by 40%. For each parameter analyzed (eg, D2%), the difference in dose, averaged over all patients, between automatic segmentation structures edited by RO_A and the same structure manually drawn by RO_A was <1.5% of the prescribed dose. The mean heart dose was reliable for the unedited heart segmentation, and for right-sided treatments, automatic segmentation was adequate for treatment planning with 3-D conformal tangential fields. CONCLUSIONS: Automatic segmentation for prone breast radiotherapy stratified by body mass index and breast cup size improved segmentation accuracy for the heart and coronary vessels compared to breast volume sampling. A significant reduction in contouring time can be achieved by using automatic segmentation.

Electromagnetic Transponder Localization and Real-Time Tracking for Prostate Cancer Radiation Therapy: Clinical Impact of Metallic Hip Prostheses.

PURPOSE: Our purpose was to assess the ability of electromagnetic transponders (EMTs) to localize and track movements in patients with prostate cancer (PCa) with metallic hip prostheses (MHPs) treated with curative radiation therapy (RT). METHODS AND MATERIALS: Data sets of 8 PCa patients with MHPs (3 bilateral and 5 unilateral) treated between 2016 and 2018 with RT and EMT tracking were retrospectively assessed. The distances between the 3 EMTs (apex to left, left to right, right to apex) and the isocenter were calculated both on planning computed tomography (CT) and cone beam CT (CBCT) at the first treatment fraction and compared with data reported by Calypso. EMT position and treatment interruptions triggered by Calypso were analyzed for all evaluable treatment fractions (n = 120). Localization accuracy was quantified by recording the geometric residual value (expected limit ≤0.2 cm) at the RT setup. RESULTS: The Calypso system was able to localize and track prostate position without any detectable interference from MHP. For every treatment fraction, the agreement between the CBCT images and Calypso guidance was optimal, with EMTs always within the defined tolerance (ie, CT-Calypso or CBCT-Calypso measured differences in inter-EMT distances within 0.3 cm). EMT to isocenter distances measured by Calypso reproduced CT data and were confirmed on CBCT scans. During RT, the EMT centroid exceeded the threshold 24 times (20% of all fractions): 5 times in the left-right, 15 times in the anteroposterior, and 4 times in the superoinferior directions. The largest motions recorded were in the anteroposterior axis: 0.6 cm anteriorly and 0.5 cm posteriorly in patients with unilateral and bilateral MHP, respectively. CONCLUSIONS: Our study represents the first clinical experience assessing the localization and tracking accuracy of Calypso EMTs during curative RT of patients with PCa with unilateral or bilateral MHP.

The mean absolute dose deviation-A common metric for the evaluation of dose-volume histograms in radiation therapy.

Radiation therapy needs to balance between delivering a high dose to targets and the lowest possible dose to the organs at risk. Dose-volume histograms (DVHs) summarize the distribution of radiation doses in the irradiated structures. The interpretation can however be a challenge when the number of structures is high. We propose the use of a simple summary metric. We define the mean absolute dose deviation (MADD) as the average of absolute differences between a DVH and a reference dose. The properties are evaluated through numerical analysis. Calculus trivially shows the identity of the MADD and the area between curves, between DVH and reference dose. Computation of the MADD is the same regardless of structures' designation, whether organ at risk or target, on the same dose scale. Basic calculus properties open the perspective of applying the MADD to the evaluation of treatment plans.

Image-guided total-body irradiation with a movable electronic portal imaging device for bone marrow transplant conditioning.

INTRODUCTION: To prevent radiation pneumonitis following total body irradiation (TBI) clinicians usually use lung shield blocks. The correct position of these shields relative to the patient's lungs is usually verified via mega-voltage imaging and computed radiographic (CR) films. In order to improve this time-consuming procedure, we developed in our department a dedicated, movable, real-time imaging system for image-guided TBI. MATERIAL & METHODS: The system consists of an electronic portal imaging device (EPID) mounted on a dedicated support whose motion along a rail can be controlled from the linac console outside the bunker room. Images are acquired online using a stand-alone console. To test the system efficacy we retrospectively analyzed data of lung blocks positioning from two groups of 10 patients imaged with EPID or CR-films, respectively. RESULTS: The median number of portal images per fraction was 2 (range 1-5) and 1 (range 1-2) for the EPID and the CR-film system, respectively. The minimum time required for an EPID image acquisition, without interpretation and no need of patient position correction in the bunker, was 20seconds against 214seconds for the CR-film. Lung shielding positioning in the right-left and superior-inferior directions was improved using the EPID system (p<0.01). CONCLUSIONS: Compared to CR-films, our movable real-time imaging EPID system is a simple technical solution able to reduce the minimum imaging time for lung shielding by a factor of 10. With the increased possibility to acquire more images as compared to CR-film system the EPID system has the potential to improve patient alignment, as well as patient's comfort and overall setup time.

Clinical experience with lung-specific electromagnetic transponders for real-time tumor tracking in lung stereotactic body radiotherapy.

BACKGROUND AND PURPOSES: Motion management is crucial for optimal stereotactic body radiotherapy (SBRT) of moving targets. We aimed to describe our clinical experience with real-time tracking of lung-specific electromagnetic transponders (EMTs) for SBRT of early stage non-small cell lung cancer in free-breathing (FB) or deep inspiration breath-hold (DIBH). MATERIAL AND METHODS: Seven patients were implanted with EMTs. Simulation for SBRT was performed in FB and in DIBH. We prescribed 60 Gy in 3, 5 or 8 fractions to the tumor and delivered SBRT with volumetric modulated arcs and a 6 MV flattening filter free photon beam. Patients' setup at the linac was performed using EMT positions and cone-beam CT (CBCT) verification. Four patients were treated in DIBH because of a dosimetric benefit. We analysed patient alignment and treatment delivery parameters using DIBH or FB and EMT real-time tracking. RESULTS: There were no complications from the EMT implantation. Visual inspection of CBCT before and/or after SBRT revealed good alignment of structures and EMTs. The median setup time was 9.8 min (range: 4.6-34.1 min) and the median session time was 14.7 min (range: 7.3-36.5 min). EMT positions in lungs remained stable during overall treatment and allowed real-time tracking both in FB and in DIBH SBRT. The treatment beam was gated when EMT centroid position exceeded tolerance thresholds ensuring correct delivery of radiation to the tumor. CONCLUSION: Using EMTs for real-time tracking of tumor motion during lung SBRT proved to be safe, accurate and easy to integrate clinically for treatments in FB or DIBH.

Salvage reirradiation for local failure of prostate cancer after curative radiation therapy: Association of rectal toxicity with dose distribution and normal-tissue complication probability models.

PURPOSE: This study aimed to assess the impact of radiation dose on rectal toxicity after salvage external beam radiation therapy (EBRT) with or without a brachytherapy boost for exclusive local failures after the primary EBRT for prostate cancer. METHODS AND MATERIALS: Fourteen patients with no severe residual late toxicity after primary EBRT ± brachytherapy were reirradiated after a median time interval of 6.1 years. The median normalized total dose in 2 Gy fractions (NTD2Gy, α/ß ratio = 1.5 Gy for prostate cancer cells) was 74 Gy at primary EBRT and 85.1 Gy at reirradiation. Rectal dose-volume histograms (converted to NTD2Gy_alpha/beta = 3 Gy) and the corresponding normal-tissue complication probability (NTCP) values for gastrointestinal (GI) toxicity were evaluated for 2 groups: High GI toxicity (grade ≥3) and low GI toxicity (grade ≤2). RESULTS: The 5-year grade ≥3 GI toxicity-free survival rate was 57.1%. The median rectal V70Gy and maximum dose to 1 cm3 (D1ccrect) at primary EBRT were both predictive for grade ≥3 GI toxicity (9% vs 0%; P = .04 and 72.2 Gy vs 66.8 Gy; P < .01, respectively). When adding primary radiation therapy (RT) and reirradiation plans, the median D1ccrect was 139.8 Gy versus 126.7 Gy (P < .01) for high and low GI toxicity groups. NTCP >10% at primary RT was predictive for high GI toxicity at reirradiation (P < .05). CONCLUSIONS: Even in the absence of residual toxicity after primary RT, rectal doses >70 Gy and NTCP >10% calculated for a first irradiation may be associated with a higher risk of developing high GI toxicity at reirradiation with a possible D1ccrect threshold of 130 Gy.

Improving 3D-printing of megavoltage X-rays radiotherapy bolus with surface-scanner.

BACKGROUND: Computed tomography (CT) data used for patient radiotherapy planning can nowadays be used to create 3D-printed boluses. Nevertheless, this methodology requires a second CT scan and planning process when immobilization masks are used in order to fit the bolus under it for treatment. This study investigates the use of a high-grade surface-scanner to produce, prior to the planning CT scan, a 3D-printed bolus in order to increase the workflow efficiency, improve treatment quality and avoid extra radiation dose to the patient. METHODS: The scanner capabilities were tested on a phantom and on volunteers. A phantom was used to produce boluses in the orbital region either from CT data (resolution ≈1 mm), or from surface-scanner images (resolution 0.05 mm). Several 3D-printing techniques and materials were tested. To quantify which boluses fit best, they were placed on the phantom and scanned by CT. Hounsfield Unit (HU) profiles were traced perpendicular to the phantom's surface. The minimum HU in the profiles was compared to the HU values for calibrated air-gaps. Boluses were then created from surface images of volunteers to verify the feasibility of surface-scanner use in-vivo. RESULTS: Phantom based tests showed a better fit of boluses modeled from surface-scanner than from CT data. Maximum bolus-to-skin air gaps were 1-2 mm using CT models and always < 0.6 mm using surface-scanner models. Tests on volunteers showed good and comfortable fit of boluses produced from surface-scanner images acquired in 0.6 to 7 min. Even in complex surface regions of the body such as ears and fingers, the high-resolution surface-scanner was able to acquire good models. A breast bolus model generated from images acquired in deep inspiration breath hold was also successful. None of the 3D-printed bolus using surface-scanner models required enlarging or shrinking of the initial model acquired in-vivo. CONCLUSIONS: Regardless of the material or printing technique, 3D-printed boluses created from high-resolution surface-scanner images proved to be superior in fitting compared to boluses created from CT data. Tests on volunteers were promising, indicating the possibility to improve overall radiotherapy treatments, primarily for megavoltage X-rays, using bolus modeled from a high-resolution surface-scanner even in regions of complex surface anatomy.