A competing risk analysis of the patterns and risk factors of recurrence in early-stage non-small cell lung cancer treated with stereotactic ablative radiotherapy.

INTRODUCTION: To assess patterns of recurrence after stereotactic ablative radiotherapy (SABR) in patient ineligible to surgery with early-stage non-small cell lung cancer (ES-NSCLC), report survival and treatment after first recurrence. METHODS: We performed a retrospective analysis on 1068 patients with ES-NSCLC and 1143 lesions. Between group differences were estimated using competing risk analysis and cause-specific hazard ratios were calculated. Overall survival (OS) after first recurrence was calculated. RESULTS: Median follow-up was 37.6 months. Univariate analysis demonstrated that ultra-central location was associated with higher risk of regional recurrence (RR) and distant metastasis (DM) (p = 0.004 and 0.01). Central lesions were associated with higher risk of local recurrence (LR) and RR (p < 0.001). Ultra-central lesions were associated with shorter OS (p = 0.002) compared to peripheral lesions. In multivariate analysis, central location was the only factor associated with increased LR and RR risks (p = 0.016 and 0.005). Median OS after first recurrence was 14.8 months. There was no difference in OS after first recurrence between ultra-central, central, and peripheral lesions (p = 0.83). Patients who received a second SABR course had an OS of 51.3 months, compared to 19.5 months with systemic therapy and 8.1 months with supportive care (p < 0.0001). DISCUSSION: The main prognostic factor for LR and RR risks was central location. Ultra-central and central tumors might benefit from treatment intensification strategies such as dose escalation and/or addition of systemic therapy to improve radiotherapy outcomes. After a first recurrence post SABR, patients with contralateral lung recurrences and those who were eligible to receive a second course of SABR had improved OS.

Technical note: Consistency of IAEA's TRS-483 and AAPM's extended TG-51 protocols for clinical reference dosimetry of the CyberKnife M6 machine.

BACKGROUND: While IAEA's TRS-483 code of practice is adapted for the calibration of CyberKnife machines, AAPM's TG-51 is still the protocol recommended by the manufacturer for their calibration. The differences between both protocols could lead to differences in absorbed dose to water during the calibration process. PURPOSE: The aims of this work are to evaluate the difference resulting from the application of TG-51 (including the manufacturer's adaptations) and TRS-483 in terms of absorbed dose to water for a CyberKnife M6, and to evaluate the consistency of TRS-483. METHODS: Measurements are performed on a CyberKnife M6 unit under machine-specific reference conditions using a calibrated Exradin A12 ionization chamber. Monte Carlo (MC) simulations are performed to estimate k Q msr , Q 0 f msr , f ref $k_{Q_{\mathrm{msr}},Q_0}^{f_{\mathrm{msr}},f_{\mathrm{ref}}}$ and k vol $k_{\text{vol}}$ using a fully modeled detector and an optimized CyberKnife M6 beam model. The latter is also estimated experimentally. Differences between the adapted TG-51 and TRS-483 protocols are identified and their impact is quantified. RESULTS: When using an in-house experimentally-evaluated volume averaging correction factor, a difference of 0.11% in terms of absorbed dose to water per monitor unit is observed when applying both protocols. This disparity is solely associated to the difference in beam quality correction factor. If a generic volume averaging correction factor is used during the application of TRS-483, the difference in calibration increases to 0.14%. In both cases, the disparity is not statistically significant according to TRS-483's reported uncertainties on their beam quality correction factor (i.e., 1%). MC results lead to k Q msr , Q 0 f msr , f ref = 1.0004 ± 0.0002 $k_{Q_{\mathrm{msr}},Q_0}^{f_{\mathrm{msr}},f_{\mathrm{ref}}}=1.0004\pm 0.0002$ and k vol = 1.0072 ± 0.0009 $k_{\text{vol}}=1.0072\pm 0.0009$ . Results illustrate that the generic beam quality correction factor provided in the TRS-483 might be overestimated by 0.36% compared to our specific model and that this overestimation could be due to the volume averaging component. CONCLUSIONS: For clinical reference dosimetry of the CyberKnife M6, the application of TRS-483 is found to be consistent with TG-51.

Large-scale dosimetric assessment of Monte Carlo recalculated doses for lung robotic stereotactic body radiation therapy.

Owing to its short computation time and simplicity, the Ray-Tracing algorithm (RAT) has long been used to calculate dose distributions for the CyberKnife system. However, it is known that RAT fails to fully account for tissue heterogeneity and is therefore inaccurate in the lung. The aim of this study is to make a dosimetric assessment of 219 non-small cell lung cancer CyberKnife plans by recalculating their dose distributions using an independent Monte Carlo (MC) method. For plans initially calculated by RAT without heterogeneity corrections, target coverage was found to be significantly compromised when considering MC doses. Only 35.4% of plans were found to comply to their prescription doses. If the normal tissue dose limits were respected in the treatment planning dose, the MC recalculated dose did not exceed these limits in over 97% of the plans. Comparison of RAT and recalculated-MC doses confirmed the overestimation of RAT doses observed in previous studies. An inverse correlation between the RAT/MC dose ratio and the target size was also found to be statistically significant (p<10-4), consistent with other studies. In addition, the inaccuracy and variability in target coverage incurred from dose calculations using RAT without heterogeneity corrections was demonstrated. On average, no clinically relevant differences were observed between MC-calculated dose-to-water and dose-to-medium for all tissues investigated (⩽1%). Patients receiving a dose D95% larger than 119 Gy in EQD210 (or ≈52 Gy in 3 fractions) as recalculated by MC were observed to have significantly superior loco-regional progression-free survival rates (p=0.02) with a hazard ratio of 3.45 (95%CI: 1.14-10.5).

Comparing local control and distant metastasis in NSCLC patients between CyberKnife and conventional SBRT.

BACKGROUND AND PURPOSE: Previous literature suggests that the dose proximally outside the PTV could have an impact on the incidence of distant metastasis (DM) after SBRT in stage I NSCLC patients. We investigated this observation (along with local failure) in deliveries made by different treatment modalities: robotic mounted linac SBRT (CyberKnife) vs conventional SBRT (VMAT/CRT). MATERIALS AND METHODS: This study included 422 stage I NSCLC patients from 2 institutions who received SBRT: 217 treated conventionally and 205 with CyberKnife. The dose behavior outside the PTV of both sub-cohorts were compared by analyzing the mean dose in continuous shells extending 1, 2, 3, …, 100 mm from the PTV. Kaplan-Meier analysis was performed between the two sub-cohorts with respect to DM-free survival and local progression-free survival. A multivariable Cox proportional hazards model was fitted to the combined cohort (n = 422) with respect to DM incidence and local failure. RESULTS: The shell-averaged dose fall-off beyond the PTV was found to be significantly more modest in CyberKnife plans than in conventional SBRT plans. In a 30 mm shell around the PTV, the mean dose delivered with CyberKnife (38.1 Gy) is significantly larger than with VMAT/CRT (22.8 Gy, p<10-8). For 95% of CyberKnife plans, this region receives a mean dose larger than the 21 Gy threshold dose discovered in our previous study. In contrast, this occurs for only 75% of VMAT/CRT plans. The DM-free survival of the entire CyberKnife cohort is superior to that of the 25% of VMAT/CRT patients receiving less than the threshold dose (VMAT/CRT<21Gy), with a hazard ratio of 5.3 (95% CI: 3.0-9.3, p<10-8). The 2 year DM-free survival rates were 87% (95% CI: 81%-91%) and 44% (95% CI: 28%-58%) for CyberKnife and the below-threshold dose conventional cohorts, respectively. A multivariable analysis of the combined cohort resulted in the confirmation that threshold dose was a significant predictor of DM(HR = 0.28, 95% CI: 0.15-0.55, p<10-3) when adjusted for other clinical factors. CyberKnife was also found to be superior to the entire VMAT/CRT with respect to local control (HR = 3.44, CI: 1.6-7.3). The 2-year local progression-free survival rates for the CyberKnife cohort and the VMAT/CRT cohort were 96% (95% CI: 92%-98%) and 88% (95% CI: 82%-92%) respectively. CONCLUSIONS: In standard-of-care CyberKnife treatments, dose distributions that aid distant control are achieved 95% of the time. Although similar doses could be physically achieved by conventional SBRT, this is not always the case with current prescription practices, resulting in worse DM outcomes for 25% of conventional SBRT patients. Furthermore, CyberKnife was found to provide superior local control compared to VMAT/CRT.

A dosimetric parameter to limit chest wall toxicity in SABR of NSCLC.

OBJECTIVE: Chest wall (CW) toxicity (rib fracture and/or pain) is a recognized complication of stereotactic ablative radiotherapy (SABR) for non-small-cell lung cancer. The aim of this study was to evaluate the frequency of CW toxicity following SABR and to propose a new dosimetric parameter. METHODS: We reviewed the charts and SABR plans from patients treated for T1-T2N0 peripheral non-small-cell lung cancer between 2009 and 2015. The CW structure was created through a 3-cm expansion of the lung. The median dose delivered to the planning target volume was 60 Gy. SABR was delivered in three fractions for patients with CW V30 < 30 cm3. If the CW V30 exceeded 30 cm3, five fractions were used, and the plan was optimized based on CW V37 (biologically equivalent to the V30 of three-fraction plans). RESULTS: In 6 years, 361 lesions from 356 patients were treated (3 fractions: 297; 5 fractions: 64). The median follow-up was 16 months. 23 patients (6.5%) developed CW toxicity after a median time of 10 months following treatment. The mean CW V30/V37 was 21 cm3 for patients with CW toxicity and 17 cm3 for patients without toxicity (p < 0.05). The 2-year local control and the CW toxicity rates were similar, whether patients received three or five fractions (97% vs 96% and 7% vs 5%). CONCLUSION: When the CW V30 is >30 cm3, altered fractionation combined with V37 optimization can limit CW toxicity. Advances in knowledge: The CW V37 is a suggested dosimetric parameter adapted to fractionation that may potentially limit CW toxicity after lung SABR.

Larynx motion considerations in partial larynx volumetric modulated arc therapy for early glottic cancer.

INTRODUCTION: To assess laryngeal motion in early glottic cancer in order to determine safe margins for partial larynx volumetric modulated arc therapy (PL-VMAT), and to quantify dosimetric advantages of PL-VMAT. METHODS: This prospective study included T1-2N0 glottic cancers treated with whole larynx VMAT (WL-VMAT). Pre- and mid-treatment 4D-computed tomography (4D-CT) and dynamic magnetic resonance imaging (MRI) allowed for assessment of larynx swallowing and respiratory motion. For 10 patients with lateralized lesions, PL-VMAT plans were calculated using margins derived from 4D-CT analysis. RESULTS: Twenty patients were accrued from 2014 to 2016. Mean amplitude of larynx swallowing excursion was 23 mm and 6 mm in the superior and anterior directions, respectively. Mean respiratory motion reached 4 mm and 2 mm in superior-inferior and antero-posterior directions, respectively. Pre-treatment 4D-CT analysis identified one patient with planning CT acquired during swallowing. Mid-treatment 4D-CT revealed larynx shift relative to vertebrae in 30% of cases. PL-VMAT allowed for significant reduction of mean doses to ipsilateral carotid, contralateral carotid, thyroid gland, contralateral arytenoid and larynx. Using 8 mm internal margin for PL-VMAT, swallowing resulted in clinical target volume excursion beyond 95% isodose line during ≤1.5% of total treatment time in all patients. CONCLUSION: Although swallowing motion is rare, rapid and easily suppressed by patients, there is a risk of systematic miss-targeting if planning CT is acquired during swallowing. Larynx position shift relative to vertebrae occurs in 1/3 of patients over the course of radiotherapy. With soft-tissue image guidance and margins accounting for respiratory motion, PL-VMAT allows safe reduction of dose to organs at risk.

The impacts of mid-treatment CBCT-guided patient repositioning on target coverage during lung VMAT.

INTRODUCTION: The purpose of this study is quantify intrafraction motion (IFM) during lung volumetric-modulated arc therapy (VMAT) and evaluate the impact of mid-treatment cone beam computed tomography (CBCT)-guided patient repositioning on target coverage. METHOD: This analysis included lung tumours treated with VMAT to 50-60 Gy in 3-5 fractions. Treatment planning was based on four-dimensional CT scans from which internal tumour volumes (ITV) were derived. An isotropic 5 mm margin was added to obtain the final planning target volume (PTV). Patients were treated supine with a customized dual vacuum immobilization device (BodyFIX, Elekta, Sweden). All patients underwent pre and mid-treatment CBCTs. Following each CBCT, a rigid registration was performed by a radiation oncologist. IFM was defined as the target displacement from pre to mid-treatment CBCT. For patients with an IFM vector ≥5 mm, a post hoc dose calculation analysis was performed to assess the dosimetric impact of CBCT-guided repositioning. RESULTS: Ninety-seven patients (367 fractions) were included. Mean (±SD) overall treatment time was 53:02 ± 13:08 min. Mean time for mid-treatment CBCT scan acquisition and patient repositioning was 15:49 ± 4:14 min. Mean IFM vector was 1.5 ± 1.4 mm (max = 8.1 mm) and was <5 mm in 354/367 (96%) of fractions. For all 13 fractions with an IFM vector ≥5 mm, dose calculation analysis of worst-case scenario indicates that ITV coverage would have remained ≥95% without mid-treatment repositioning. CONCLUSION: For 96% of fractions, the IFM vector was within the 5 mm PTV margin. Mid-treatment CBCT-guided couch repositioning did not significantly impact ITV coverage and prolonged treatment duration.

Reproducibility of a Noninvasive System for Eye Positioning and Monitoring in Stereotactic Radiotherapy of Ocular Melanoma.

PURPOSE: Our preferred treatment for juxtapapillary choroidal melanoma is stereotactic radiotherapy. We aim to describe our immobilization system and quantify its reproducibility. MATERIALS AND METHODS: Patients were identified in our radiosurgery database. Patients were imaged at computed tomography simulator with an in-house system which allows visual monitoring of the eye as the patient fixates a small target. All patients were reimaged at least once prior to and/or during radiotherapy. The patients were treated on the CyberKnife system, 60 Gy in 10 daily fractions, using skull tracking in conjunction with our visual monitoring system. In order to quantify the reproducibility of the eye immobilization system, computed tomography scans were coregistered using rigid 6-dimensional skull registration. Using the coregistered scans, x, y, and z displacements of the lens/optic nerve insertion were measured. From these displacements, 3-dimensional vectors were calculated. RESULTS: Thirty-four patients were treated from October 2010 to September 2015. Thirty-nine coregistrations were performed using 73 scans (2-3 scans per patient). The mean displacements of lens and optic nerve insertion were 0.1 and 0.0 mm. The median 3-dimensional displacements (absolute value) of lens and nerve insertion were 0.8 and 0.7 mm (standard deviation: 0.5 and 0.6 mm). Ninety-eight percent of 3-dimensional displacements were below 2 mm (maximum 2.4 mm). The calculated planning target volume (PTV) margins were 0.8, 1.4, and 1.5 mm in the anterior-posterior, craniocaudal, and right-left axes, respectively. Following this analysis, no further changes have been applied to our planning margin of 2 to 2.5 mm as it is also meant to account for uncertainties in magnetic resonance imaging to computed tomography registration, skull tracking, and also contouring variability. CONCLUSION: We have found our stereotactic eye immobilization system to be highly reproducible (<1 mm) and free of systematic error.

How Low Should You Go: Choice of Minimum Dose Prescription in Cranial Radiosurgery.

BACKGROUND:  In radiosurgery, the convention has been to prescribe radiation dose to a "covering isodose volume". This is presumed to be the minimum dose received by the entire tumor. Our purpose was to review our practice, assess different means of specifying a prescription isodose, and test how reliable they were in the face of various calculation methodologies. METHODS: Different minimum doses were calculated using three calculation methods for 20 brain targets and compared to the original physician intent. Monte Carlo (MC) calculations were run down to 2% (1 sigma) statistics. Voxel size depended on the imaging field of view and the calculation engine. For pencil beam convolution ("finite size pencil beam" - FSPB) calculations with or without heterogeneity correction (Methods 1-2), the calculation grid matched the CT scan resolution. For MC calculations (Method 3), the highest available in-plane resolution was 256 x 256 pixels. The median voxel volume was thus 0.58 mm(3) (0.47 to 0.95 mm(3)) for FSPB and 2.3 mm(3) (1.87 to 3.80) for MC. RESULTS: The absolute minimum target dose varied substantially between the three calculation methods - up to 25% difference between Methods 1 and 3. The differences were reduced when comparing near-minimum doses with absolute minimal volumes ΔV, DPTV-ΔV. The median difference in the isodose covering the PTV-0.03 cm(3) was 0% for Methods 1 and 2 and 3.6% for Methods 1 and 3. The median difference in the isodose covering the PTV-0.01 cm(3) was 0% for Methods 1 and 2 and 2.2% for Methods 1 and 3. In our data, the smaller the volume in which the minimum dose is calculated, the more sensitive this calculation was to dose calculation parameters. The standard deviation of the difference between physician intent and the isodose covering the PTV-0.01 cm(3) was 2.9% (range from -3.3% to 9.3%). CONCLUSION: In radiosurgery, absolute minimum doses are sensitive to changes in dose calculation grids and dose calculation algorithms. Based on our experience, standardizing dose prescription to the isodose volume covering the PTV-0.01 cm(3) or the PTV-0.03 cm(3) would have little impact on clinical practice and would be relatively insensitive to dose calculation parameters.

Long-term quality of life in early-stage non-small cell lung cancer patients treated with robotic stereotactic ablative radiation therapy.

PURPOSE: The purpose of this study was to prospectively evaluate the quality of life (QoL) and pulmonary function of patients with early-stage non-small cell lung cancer treated with robotic stereotactic ablative radiation therapy (SABR). METHODS AND MATERIALS: Eligible patients all had histologically confirmed stage I non-small cell lung cancer and were not surgical candidates because of poor pulmonary function, comorbidities, or refusal of surgery. SABR was delivered at a median dose of 60 Gy in 3 fractions for peripheral tumors and 50 Gy in 4 or 5 fractions for central tumors. QoL was scored using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (QLQ-C30) and Lung Cancer-13 questionnaires. Pulmonary function tests (PFTs) included forced expiratory volume in 1 second (FEV1) and lung diffusion capacity. Changes over time in QoL scores and PFTs were tested with nonparametric tests for longitudinal data. Local control, survival, and toxicities are also presented. RESULTS: From January 2010 to May 2013, 45 patients were enrolled. Median follow-up was 41 months. QLQ-C30 mean baseline scores for global QoL and physical functioning were 66 ± 20% and 73 ± 22%. Multilevel analyses showed no statistically and clinically significant (10-point change) deterioration in any of the QoL scores after SABR. Mean baseline FEV1 was 1.39 ± 0.51 L, and mean lung diffusion capacity was 63 ± 25% of predicted. We saw no significant change in PFTs at any time point. At 3 years, local control, disease-free survival, and overall survival were, respectively, 94%, 67%, and 75%. CONCLUSIONS: In nonsurgical patients with multiple comorbidities, lung SABR achieves long-term local control while maintaining QoL and pulmonary function.

Excellent Cancer Outcomes Following Patient-adapted Robotic Lung SBRT But a Case for Caution in Idiopathic Pulmonary Fibrosis.

The aim of this study is to report outcomes and prognostic factors for early stage non-small cell lung cancer treated with patient-adapted Cyberknife stereotactic body radiotherapy. A retrospective analysis of 150 patients with T1-2N0 non-small cell lung cancer treated with stereotactic body radiotherapy was conducted. An algorithm based on tumor and patient's characteristics was used to orient patients towards soft tissue (Xsight Lung), fiducials or adjacent bone (Xsight Spine) tracking. Median biological effective dose without correction for tissue inhomogeneities was 180 Gy10 for peripheral tumors and 113 Gy10 for central tumors. Median follow-up was 22 months. Actuarial 2 years local control, overall survival and disease-specific survival were respectively 96%, 87% and 95%. Every 1 cm increase in tumor diameter was associated with a relative risk for regional or distant relapse of 2 (95%CI = 1.2-3.6, p = 0.009). With doses ≥132 Gy10 and <132 Gy10, local control was 98% vs. 82% (p = 0.07), disease-specific survival 97% vs. 78% (p = 0.02) and overall survival 93% vs. 76% (p = 0.01), respectively. Better disease-specific survival and a trend for better overall survival was observed for peripheral vs. central tumors (96% vs. 79%, p = 0.05 and 92% vs. 74%, p = 0.08, respectively). A higher Charlson comordibity score (≥4) predicted lower overall survival (79% vs. 98%, p = 0.01). Toxicities included 3 patients with idiopathic pulmonary fibrosis who developed grade 5 pneumonitis and 2 patients with grade 3 pneumonitis. We therefore report excellent local control and disease-specific survival following patient-adapted Cyberknife lung stereotactic body radiotherapy. Although toxicities were in general minimal, patients with pulmonary fibrosis might be at greater risk of severe complications. Small size, peripheral location, dose ≥ 132 Gy10 and a low Charlson co-morbidity score seem to be associated with better outcomes.

Predictive parameters of CyberKnife fiducial-less (XSight Lung) applicability for treatment of early non-small cell lung cancer: a single-center experience.

PURPOSE: To determine which parameters allow for CyberKnife fiducial-less tumor tracking in stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer. METHODS AND MATERIALS: A total of 133 lung SBRT patients were preselected for direct soft-tissue tracking based on manufacturer recommendations (peripherally located tumors ≥1.5 cm with a dense appearance) and staff experience. Patients underwent a tumor visualization test to verify adequate detection by the tracking system (orthogonal radiographs). An analysis of potential predictors of successful tumor tracking was conducted looking at: tumor stage, size, histology, tumor projection on the vertebral column or mediastinum, distance to the diaphragm, lung-to-soft tissue ratio, and patient body mass index. RESULTS: Tumor visualization was satisfactory for 88 patients (66%) and unsatisfactory for 45 patients (34%). Median time to treatment start was 6 days in the success group (range, 2-18 days) and 15 days (range, 3-63 days) in the failure group. A stage T2 (P=.04), larger tumor size (volume of 15.3 cm(3) vs 6.5 cm(3) in success and failure group, respectively) (P<.0001), and higher tumor density (0.86 g/cm(3) vs 0.79 g/cm(3)) were predictive of adequate detection. There was a 63% decrease in failure risk with every 1-cm increase in maximum tumor dimension (relative risk for failure = 0.37, CI=0.23-0.60, P=.001). A diameter of 3.6 cm predicted a success probability of 80%. Histology, lung-to-soft tissue ratio, distance to diaphragm, patient's body mass index, and tumor projection on vertebral column and mediastinum were not found to be predictive of success. CONCLUSIONS: Tumor size, volume, and density were the most predictive factors of a successful XSight Lung tumor tracking. Tumors >3.5 cm have ≥80% chance of being adequately visualized and therefore should all be considered for direct tumor tracking.

Long-term results of radiosurgery for cerebral arteriovenous malformations.

BACKGROUND: Stereotactic radiosurgery (SRS) is known to safely result in a high obliteration rate for small and medium sized arteriovenous malformations (AVM). OBJECTIVE: To evaluate the long-term outcome of patients treated with SRS, with special emphasis given to obliteration and toxicity rates. METHODS: We performed a review of 43 cerebral AVM patients, treated from 1998 to 2008 with a single SRS dose ranging from 21-25 Gy. Of these, 37 had a minimal follow-up of one year. Medical files were reviewed to assess patient and AVM characteristics, the SRS treatment, therapy prior to SRS, the obliteration rate and toxicities. Whenever necessary, outcome data was supplemented by telephone interviews with the patient or treating physician. RESULTS: AVM size was ≥3cm in diameter in 21% of patients. Five patients (11.6%) underwent surgery prior to SRS and 31 patients (72.1%) received one or more embolizations prior to SRS. Of the patients followed with angiography ≥1 year post-SRS, 89% (33/37) had a complete obliteration of the nidus, after a median time of 24.7 months post-treatment. Embolization prior to SRS was not predictive of outcome. One patient suffered a non-fatal haemorrhage between treatment and obliteration. The rate of symptomatic radiation-induced radiological changes was 8.1%. CONCLUSION: Our study shows both obliteration and complication rates in the upper limit of those reported in the literature. SRS seems an attractive treatment option for small AVMs. Unlike other reports, the prior use of embolization did not impact negatively on obliteration rates.

Bone marrow-sparing intensity-modulated radiation therapy for Stage I seminoma.

BACKGROUND: A direct association between radiotherapy dose, side-effects and secondary cancers has been described in patients with seminoma. A treatment planning study was performed in order to compare computed tomography-based traditional radiotherapy (CT-tRT) versus bone marrow-sparing intensity-modulated radiation therapy (BMS-IMRT) in patients with Stage I seminoma. MATERIAL AND METHODS: We optimized in 10 patients a CT-tRT and a BMS-IMRT treatment plan to deliver 20 Gy to the para-aortic nodes. CT-tRT and IMRT consisted of anteroposterior-posterioranterior parallel-opposed and seven non-opposed coplanar fields using 16 and 6-MV photon energies, respectively. Dose-Volume Histograms for clinical target volume (CTV), planning target volume (PTV) and organs at risk (OARs) were compared for both techniques using Wilcoxon matched-pair signed rank-test. RESULTS: D(mean) to CTV and PTV were similar for both techniques, even if CT-tRT showed a slightly improved target coverage in terms of PTV-D(95%) (19.7 vs. 19.5 Gy, p = 0.005) and PTV-V(95%) (100 vs. 99.7%, p = 0.011) compared to BMS-IMRT. BMS-IMRT resulted in a significant reduction (5.2 Gy, p = 0.005) in the D(mean) to the active bone marrow (ABM). The V(100%) and V(75%) of the OARs were reduced with BMS-IMRT by: ABM-V(100%) = 51.7% and ABM-V(75%) = 42.3%; bowel-V(100%) = 15.7% and bowel-V(75%) = 16.8%; stomach-V(100%) = 22% and stomach-V(75%) = 27.7%; pancreas-V(100%) = 37.1% and pancreas-V(75%) = 35.9% (p = 0.005 for all variables). CONCLUSIONS: BMS-IMRT reduces markedly the dose to the OARs compared to CT-tRT. This should translate into a reduction in acute and long-term toxicity, as well as into the risk of secondary solid and hematological cancers.