Isotropic Margin Research Articles

Impact of intrafraction changes in delivered dose of the day for prostate cancer patients treated with stereotactic body radiotherapy via MR-Linac.

The purpose of this study is to evaluate the impact of intrafraction pelvic motion by comparing the adapted plan dose (APD) and the computed delivered dose of the day (DDOTD) for patients with prostate cancer (PCa) treated with SBRT on the MR-Linac. Twenty patients with PCa treated with MR-guided adaptive SBRT were included. A 9-field IMRT distribution was adapted based on the anatomy of the day to deliver a total prescription dose of 3000cGy in 5 fractions to the prostate plus a 5mm isotropic margin. Prostate, bladder, and rectum were re-contoured on the MR-image acquired during treatment delivery (MRBO). DDOTD was computed by propagating the dose from the daily adapted plan generated during treatment onto the MRBO. Target coverage was met for all fractions, however, computed DDOTD was significantly less than the APD (p<0.05). During an average treatment of 53min, mean bladder volume increased by 116%, which led to a significant decrease in the DDOTD bladder D40% (p<0.001). However, DDOTD to bladder 5cc was significantly higher (p<0.001) than APD. Rectum intrafraction changes were observed based on a volume change of -20% to 83% and presence of significant dose changes from APD to DDOTD for rectum D20% (p<0.05) and D1cc (p<0.0001). Intrafraction motion observed during prostate SBRT treatment on the MR-Linac have dosimetric impacts on both the target and organs at risk. Post-treatment computation using DDOTD may inform adaptation beyond anatomic changes in subsequent treatment fractions to best capitalize on MR-Linac technology and widen the therapeutic index of SBRT for PCa.

Stereotactic Ablative Radiotherapy of Ventricular Tachycardia Using Tracking: Optimized Target Definition Workflow.

Background and PurposeStereotactic arrhythmia radioablation (STAR) has been suggested as a promising therapeutic alternative in cases of failed catheter ablation for recurrent ventricular tachycardias in patients with structural heart disease. Cyberknife® robotic radiosurgery system utilizing target tracking technology is one of the available STAR treatment platforms. Tracking using implantable cardioverter-defibrillator lead tip as target surrogate marker is affected by the deformation of marker–target geometry. A simple method to account for the deformation in the target definition process is proposed.MethodsRadiotherapy planning CT series include scans at expiration and inspiration breath hold, and three free-breathing scans. All secondary series are triple registered to the primary CT: 6D/spine + 3D translation/marker + 3D translation/target surrogate—a heterogeneous structure around the left main coronary artery. The 3D translation difference between the last two registrations reflects the deformation between the marker and the target (surrogate) for the respective respiratory phase. Maximum translation differences in each direction form an anisotropic geometry deformation margin (GDM) to expand the initial single-phase clinical target volume (CTV) to create an internal target volume (ITV) in the dynamic coordinates of the marker. Alternative GDM-based target volumes were created for seven recent STAR patients and compared to the original treated planning target volumes (PTVs) as well as to analogical volumes created using deformable image registration (DIR) by MIM® and Velocity® software. Intra- and inter-observer variabilities of the triple registration process were tested as components of the final ITV to PTV margin.ResultsA margin of 2 mm has been found to cover the image registration observer variability. GDM-based target volumes are larger and shifted toward the inspiration phase relative to the original clinical volumes based on a 3-mm isotropic margin without deformation consideration. GDM-based targets are similar (mean DICE similarity coefficient range 0.80–0.87) to their equivalents based on the DIR of the primary target volume delineated by dedicated software.ConclusionThe proposed GDM method is a simple way to account for marker–target deformation-related uncertainty for tracking with Cyberknife® and better control of the risk of target underdose. The principle applies to general radiotherapy as well.

3D dose reconstruction based on in vivo dosimetry for determining the dosimetric impact of geometric variations in high-dose-rate prostate brachytherapy

IntroductionIn vivo dosimetry (IVD) can be used for source tracking (ST), i.e., estimating source positions, during brachytherapy. The aim of this study was to exploit IVD-based ST to perform 3D dose reconstruction for high-dose-rate prostate brachytherapy and to evaluate the robustness of the treatments against observed geometric variations. Materials and MethodsTwenty-three fractions of high-dose-rate prostate brachytherapy were analysed. The treatment planning was based on MRI. Time-resolved IVD was performed using a fibre-coupled scintillator. ST was retrospectively performed using the IVD measurements. The ST identified 2D positional shifts of each treatment catheter and thereby inferred updated source positions. For each fraction, the dose was recalculated based on the source-tracked catheter positions and compared with the original plan dose using differences in dose volume histogram indices. ResultsOf 352 treatment catheters, 344 had shifts of less than 5 mm. Shifts between 5 and 10 mm were observed for 3 catheters, and shifts greater than 10 mm for 2 catheters. The ST failed for 3 catheters.The maximum relative difference in clinical target volume (prostate + 3 mm isotropic margin) D90% was 5%. In one fraction, the bladder D2cm3 dose increased by 18% (1.4 Gy) due to a single source position being inside the bladder rather than nearby as planned. The max increase in urethra dose was 1.5 Gy (15%). ConclusionIVD-based 3D dose reconstruction for high-dose-rate prostate brachytherapy is feasible. The dosimetric impact of the observed catheter shifts was limited. Dose reconstruction can therefore aid in determining the dosimetric impact of geometric variations and errors in brachytherapy.

Dosimetric impact of interfraction prostate and seminal vesicle volume changes and rotation: A post-hoc analysis of a phase III randomized trial of MRI-guided versus CT-guided stereotactic body radiotherapy

Background and purposeInterfraction volumetric changes/rotations in the prostate and proximal seminal vesicles (SVs) might compromise target coverage when tight margins are used for prostate stereotactic body radiotherapy (SBRT). We investigated on-board MRI images from MRI-guided SBRT to better understand this. Materials and methodsTwenty consecutive patients treated with MRI-guided prostate SBRT (40 Gy/5 fractions) enrolled on the MRI arm of a phase III randomized trial were included. A 2 mm isotropic margin was used for prostate and proximal SVPTV. Target volume, prostate dimensions, angles of the proximal SV on axial (angle α) and sagittal view (angle θ) were measured on a 0.35 T simulation MRI and five on-board pre-treatment MRIs. Dice coefficient of the targets and target dosimetry were calculated. ResultsAll patients experienced an isotropic increase in prostate volume during SBRT (p = 0.0016): 0.1%, 9.0%, 12.1%, 15.1%, and 14.2% (median) at fractions 1–5, respectively, regardless of baseline volume, which was significantly reduced with neoadjuvant ADT (p = 0.0042). There was minimal interfraction rotation of prostate, however, considerable variations in proximal SV angle α (median 21.5°) and angle θ (median 17.6°) were seen. Median V100% was 97.5% and 87.1% for prostate and proximal SV CTV, respectively. V95%≥95% was achieved in 94% of fractions for the prostate and in 59% for proximal SV. ConclusionProstate volume consistently increased during SBRT. Interfraction prostatic rotation was minimal while rotation of the proximal SV was considerable. Prostate dosimetry was favorable, but online adaptive therapy may be indicated occasionally to account for prostatic swelling and in particular proximal SV rotations.

Application of an automatic, uncertainty model-guided, target-generating algorithm to lung stereotactic body radiotherapy.

This work evaluated a new radiotherapy target-generating framework (the αTarget algorithm) for creating internal target volumes for lung SBRT. Nineteen patients previously treated with definitive intent SBRT to the lung were identified from a clinical database. For each patient's 4DCT simulation scan, deformable image registration was used between phases of the scan in order to generate voxelized models of motion for 35 individual gross tumor volumes. These motion models were then used with a new implementation of a previously described target-generating algorithm to create new internal target volumes (αITVs). The resulting αITVs were analyzed with respect to their volume and the coverage they provided each tumor voxel per that voxel's motion model. The clinically used ITVs were similarly analyzed, and were then compared to the αITVs using paired Student's t-tests. In addition, isotropic margins were added to the αITVs in order to determine the largest margin magnitude that could be added without exceeding the volume of the clinical ITVs. The αITVs increased the target coverage provided to each tumor's 5th-percentile-most-covered-voxel an average of 50.3% compared to the clinical ITVs (p<0.0001). At the same time, the αITVs had volumes that were, on average, 31.4% smaller (p<0.0001). The differences in volume were large enough that, on average, an extra 2mm isotropic margin could be added to the αITV before it had a volume greater than the clinical ITV. The αTarget algorithm can generate more effective lung SBRT internal target volumes that provide greater coverage with smaller volumes. In combination with numerous other advantages of the framework, this effectiveness makes the αTarget algorithm a powerful new method for advanced IGRT or adaptive radiotherapy techniques.

Optimization of treatment isocenter location in single-isocenter LINAC-based stereotactic radiosurgery for management of multiple brain metastases.

Single-isocenter linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) has become a promising treatment technique for the management of multiple brain metastases. Because of the high prescription dose and steep dose gradient, SRS plans are sensitive to geometric errors, resulting in loss of target coverage and suboptimal local tumor control. Current planning techniques rely on adding a uniform and isotropic setup margin to all gross tumor volumes (GTVs) to account for rotational uncertainties. However, this setup margin may be insufficient, since the magnitude of rotational uncertainties varies and is dependent upon the distance between a GTV and the isocenter. In this study, we designed a framework to determine the optimal isocenter of a single-isocenter SRS plan for multiple brain metastases using stochastic optimization to mitigate potential errors resulting from rotational uncertainties. Planning target volumes (PTVs), defined as GTVs plus a 1-mm margin following common SRS planning convention, were assumed to be originally treated with a prescription dose and therefore covered by the prescription isodose cloud. The dose distribution, including the prescription isodose, was considered invariant assuming small rotations throughout the study. A stochastic optimization scheme was developed to determine the location of the optimal isocenter, so that the prescription dose coverage of rotated GTVs, equivalent to the intersecting volumes between the rotated GTVs and original PTVs, was maximized for any random small rotations about the isocenter. To evaluate the coverage of GTVs, the expected undergoing random rotations was approximated as the sample average undergoing a predetermined number of rotations. The expected of each individual GTV and total GTVs was then compared between the plans using the optimal isocenter and the center-of-mass (CoM), respectively. Twenty-two patients previously treated for multiple brain metastases in a single institute were included in this retrospective study. Each patient was initially treated for more than three brain metastases (mean: 7.6; range: 3-15) with the average GTV volume of 0.89 cc (range: 0.03-11.78 cc). The optimal isocenter found for each patient was significantly different from the CoM, with the average Euclidean distance between the optimal isocenter and the CoM being 4.36±2.59cm. The dose coverage to GTVs was also significantly improved (paired t-test; p<0.001) when the optimal isocenter was used, with the average of total GTVs increasing from 87.1% (standard deviation as std: 11.7%; range: 39.9-98.2%) to 94.2% (std: 5.4%; range: 77.7-99.4%). The volume of a GTV was positively correlated with the expected regardless of the isocenter used (Spearman coefficient: ; p<0.001). The distance between a GTV and the isocenter was negatively correlated with the expected when the CoM was used ( ; p=0.004), however no significant correlation was found when the optimal isocenter was used ( ; p=0.137). The proposed framework provides an effective approach to determine the optimal isocenter of single-isocenter LINAC-based SRS plans for multiple brain metastases. The implementation of the optimal isocenter results in SRS plans with consistently higher target coverage despite potential rotational uncertainties, and therefore significantly improves SRS plan robustness against random rotational uncertainties.

A novel approach for radiotherapy dose escalation in rectal cancer using online MR-guidance and rectal ultrasound gel filling – Rationale and first in human

IntroductionDose escalated radiotherapy has previously been investigated as a strategy to increase complete response rates in rectal cancer. However large safety margins are required using cone-beam computed tomography guided radiotherapy leading to high doses to organs at risk or insufficient target volume coverage in order to keep dose constraints. We herein present the first clinical application of a new technique for dose escalation in rectal cancer using online magnetic resonance (MR)-guidance and rectal ultrasound gel filling. MethodsA 73-year-old patient with distal cT3a cN0 cM0 rectal cancer was referred for definitive radiochemotherapy with the goal of organ preservation after multidisciplinary discussion. A dose of 45 Gy in 25 fractions with a stereotactic integrated boost to the primary tumor of 50 Gy with concomitant 5-fluorouracil was prescribed. Furthermore, a boost to the primary tumor with 3 Gy per fraction using the adapt-to-shape workflow on a 1.5 T MR-Linac was planned once weekly. For the boost fractions 100 cc of ultrasound gel was applied rectally in order to improve tumor visibility and distancing of uninvolved rectal mucosa. In order to determine the required planning target volume margin diagnostic scans of ten rectal cancer patients conducted with rectal ultrasound gel filling were studied. ResultsBased on the ten diagnostic scans an average isotropic margin of 4 mm was found to be sufficient to cover 95% of the target volume during an online adaptive workflow. Three boost fractions were applied, mean treatment duration was 22:34 min. Treatment was well tolerated by the patient with no more than PRO-CTCAE grade I° toxicity of any kind. The rectal ultrasound gel filling resulted in superior visibility of the tumor and reduced the dose to the involved mucosa especially in the high dose range compared with a boost plan calculated without any filling. A considerable tumor shrinkage was observed during treatment from 17.43 cc at baseline to 4 cc in week four. ConclusionThis novel method appears to be a simple but effective strategy for dose escalated radiotherapy in rectal cancer. Based on the encouraging observation, a prospective trial is currently under preparation.

Retrospective evaluation of planning margins for patients undergoing radical radiation therapy treatment for bladder cancer using volumetric modulated arc therapy and cone beam computed tomography.

IntroductionCurrent contouring guidelines for curative radiation therapy for muscle‐invasive bladder cancer (MIBC) recommend margins of 1.5–2.0 cm, applied to the clinical target volume (CTV). This study assessed whether the use of volumetric modulated arc therapy (VMAT), cone beam computed tomography (CBCT) and strict bladder preparation allowed for a reduced planning target volume (PTV) expansion, resulting in lower doses to surrounding organs at risk (OARs).MethodsDaily CBCT images for 12 patients (382 scans total) were retrospectively reviewed against four potential PTV margins created on and exported with the reference CT scan. To form the PTVs, three isotropic expansions of 0.5, 1.0 and 1.5 cm were applied to the CTV, as well as an anisotropic expansion of 1.5 cm superiorly and 1.0 cm in all other dimensions. Following treatment completion, the CBCTs were visually assessed to determine the margins encapsulating the bladder. For retrospective planning purposes, the 1.0‐cm and anisotropic margins were compared with the previously recommended margins to determine differences in OAR doses.ResultsThe 0.5‐, 1.0‐ and 1.5‐cm isotropic margins (IM) and the anisotropic margin (ANIM) covered the CTV in 46.1, 96.8, 100 and 100% of CBCTs retrospectively. Doses to OARs were significantly lower for the reduced margin plans for the small bowel, rectum and sigmoid.ConclusionBladder planning target volumes may be safely reduced. We endorse a PTV margin of 1.0cm anteriorly, posteriorly and inferiorly with 1.0–1.5 cm superiorly for radical whole bladder cases using strict bladder preparation, VMAT and pretreatment CBCTs.

Method of computing direction-dependent margins for the development of consensus contouring guidelines

BackgroundClinical target volume (CTV) contouring guidelines are frequently developed through studies in which experts contour the CTV for a representative set of cases for a given treatment site and the consensus CTVs are analyzed to generate margin recommendations. Measures of interobserver variability are used to quantify agreement between experts. In cases where an isotropic margin is not appropriate, however, there is no standard method to compute margins in specified directions that represent possible routes of tumor spread. Moreover, interobserver variability metrics are often measures of volume overlap that do not account for the dependence of disagreement on direction. To aid in the development of consensus contouring guidelines, this study demonstrates a novel method of quantifying CTV margins and interobserver variability in clinician-specified directions.MethodsThe proposed algorithm was applied to 11 cases of non-spine bone metastases to compute the consensus CTV margin in each direction of intraosseous and extraosseous disease. The median over all cases for each route of spread yielded the recommended margins. The disagreement between experts on the CTV margin was quantified by computing the median of the coefficients of variation for intraosseous and extraosseous margins.ResultsThe recommended intraosseous and extraosseous margins were 7.0 mm and 8.0 mm, respectively. The median coefficient of variation quantifying the margin disagreement between experts was 0.59 and 0.48 for intraosseous and extraosseous disease.ConclusionsThe proposed algorithm permits the generation of margin recommendations in relation to adjacent anatomy and quantifies interobserver variability in specified directions. This method can be applied to future consensus CTV contouring studies.

The role of palliative radiotherapy in the management of elderly and frail patients with advanced bladder cancer: A survey by the AIROuro-group.

Radiotherapy (RT) is rarely used in the palliative management of muscle-invasive bladder cancer (MIBC). This survey aims to explore current care patterns within the Italian Radiation Oncologist community on this topic. In 2020, the uro-oncological study group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) conducted a survey evaluating the RT role in advanced MIBC. An electronic questionnaire was administered online to the society members asking for: general considerations, patients' selection, and aim of the treatment, RT schedule and practical consideration, past and future perspective. Sixty-one questionnaires were returned (33% response rate). Most responders (62.30%) declared to work in a Center with a multidisciplinary uro-oncological team, and 8.20% to evaluate more than 20 patients with MIBC/year for palliative RT. Elderly patients were the most frequently evaluated (46.7%) and life expectancy was the most common selection criteria (44.60%). Thirty Gy in 10 fractions (58.9%), whole bladder as GTV (62.5%), PTV isotropic margins of 1.5-2cm (44.6%) and IMRT/VMAT technique (58.14%) were the most common treatment choices. Patients amenable for bladder palliative RT were most commonly referred by the urologist (43.86%) or the multidisciplinary team (38%). The reported main reasons for the low involvement of radiation oncologist in the management of MIBC patients were low attention to the palliative setting in bladder cancer (37.5%); radiation oncologist not involved in the management of these patients (32.1%); cases not discussed in the multidisciplinary board (26.8%). This survey illustrated the current use of palliative RT for patients with advanced MIBC in Italy and suggested the need for a greater involvement of radiation oncologists in their management.

Three-dimensional MRI-based treatment planning approach for non-invasive ocular proton therapy.

PurposeTo develop a high‐resolution three‐dimensional (3D) magnetic resonance imaging (MRI)‐based treatment planning approach for uveal melanomas (UM) in proton therapy.Materials/methodsFor eight patients with UM, a segmentation of the gross tumor volume (GTV) and organs‐at‐risk (OARs) was performed on T1‐ and T2‐weighted 7 Tesla MRI image data to reconstruct the patient MR‐eye. An extended contour was defined with a 2.5‐mm isotropic margin derived from the GTV. A broad beam algorithm, which we have called πDose, was implemented to calculate relative proton absorbed doses to the ipsilateral OARs. Clinically favorable gazing angles of the treated eye were assessed by calculating a global weighted‐sum objective function, which set penalties for OARs and extreme gazing angles. An optimizer, which we have named OPT’im‐Eye‐Tool, was developed to tune the parameters of the functions for sparing critical‐OARs.ResultsIn total, 441 gazing angles were simulated for every patient. Target coverage including margins was achieved in all the cases (V95% > 95%). Over the whole gazing angles solutions space, maximum dose (Dmax) to the optic nerve and the macula, and mean doses (Dmean) to the lens, the ciliary body and the sclera were calculated. A forward optimization was applied by OPT’im‐Eye‐Tool in three different prioritizations: iso‐weighted, optic nerve prioritized, and macula prioritized. In each, the function values were depicted in a selection tool to select the optimal gazing angle(s). For example, patient 4 had a T2 equatorial tumor. The optimization applied for the straight gazing angle resulted in objective function values of 0.46 (iso‐weighted situation), 0.90 (optic nerve prioritization) and 0.08 (macula prioritization) demonstrating the impact of that angle in different clinical approaches.ConclusionsThe feasibility and suitability of a 3D MRI‐based treatment planning approach have been successfully tested on a cohort of eight patients diagnosed with UM. Moreover, a gaze‐angle trade‐off dose optimization with respect to OARs sparing has been developed. Further validation of the whole treatment process is the next step in the goal to achieve both a non‐invasive and a personalized proton therapy treatment.

Statistical shape model-based planning organ-at-risk volume: application to pancreatic cancer patients

Purpose. To introduce the concept of statistical shape model (SSM)-based planning organ-at-risk volume (sPRV) for pancreatic cancer patients. Methods. A total of 120 pancreatic cancer patients were enrolled in this study. After correcting inter-patient variations in the centroid position of the planning target volume (PTV), four different SSMs were constructed by registering a deformable template model to an individual model for the stomach and duodenum. The sPRV, which focused on the following different components of the inter-patient variations, was then created: Scenario A: shape, rotational angle, volume, and centroid position; Scenario B: shape, rotational angle, and volume; Scenario C: shape and rotational angle; and Scenario D: shape. The conventional PRV (cPRV) was created by adding an isotropic margin R (3–15 mm) to the mean shape model. The corresponding sPRV was created from the SSM until the volume difference between the cPRV and sPRV was less than 1%. Thereafter, we computed the overlapping volume between the PTV and cPRV (OLc) or sPRV (OLs) in each patient. OLs being larger than OLc implies that the local shape variations in the corresponding OAR close to the PTV were large. Therefore, OLs/OLc was calculated in each patient for each R-value, and the median value of OLs/OLc was regarded as a surrogate for plan quality for each R-value. Results. For R = 3 and 5 mm, OLs/OLc exceeded 1 for the stomach and duodenum in all scenarios, with a maximum OLs/OLc of 1.21. This indicates that smaller isotropic margins did not sufficiently account for the local shape changes close to the PTV. Conclusions. Our results indicated that, in contrast to conventional PRV, SSM-based PRVs, which account for local shape changes, would result in better dose sparing for the stomach and duodenum in pancreatic cancer patients.

Prospective evaluation of probabilistic dose-escalated IMRT in prostate cancer.

BackgroundCure- and toxicity rates after intensity-modulated radiotherapy (IMRT) of prostate cancer are dose-and volume dependent. We prospectively studied the potential for organ at risk (OAR) sparing and compensation of tumor movement with the coverage probability (CovP) concept.Patients and methodsTwenty-eight prostate cancer patients (median age 70) with localized disease (cT1c–2c, N0, M0) and intermediate risk features (prostate-specific antigen [PSA] < 20, Gleason score ≤ 7b) were treated in a prospective study with the CovP concept. Planning-CTs were performed on three subsequent days to capture form changes and movement of prostate and OARs. The clinical target volume (CTV) prostate and the OARs (bladder and rectum) were contoured in each CT. The union of CTV1–3 was encompassed by an isotropic margin of 7 mm to define the internal target volume (ITV). Dose prescription/escalation depended on coverage of all CTVs within the ITV. IMRT was given in 39 fractions to 78 Gy using the Monte-Carlo algorithm. Short-term androgen deprivation was recommended and given in 78.6% of patients.ResultsLong-term toxicity was evaluated in 26/28 patients after a median follow-up of 7.1 years. At last follow-up, late bladder toxicity (Radiation Therapy Oncology Group, RTOG) G1 was observed in 14.3% of patients and late rectal toxicities (RTOG) of G1 (7.1%) and of G2 (3.6%) were observed. No higher graded toxicity occurred. After 7.1 years, biochemical control (biochemically no evidence of disease, bNED) was 95.5%, prostate cancer-specific survival and the distant metastasis-free survival after 7.1 years were 100% each.ConclusionsCovP-based IMRT was feasible in a clinical study. Dose escalation with the CovP concept was associated by a low rate of toxicity and a high efficacy regarding local and distant control.

Feasibility of Stereotactic MR-Guided Adaptive Radiotherapy in Localized Prostate Cancer

Extreme hypofractionation by use of SBRT is being frequently used in localized prostate cancer (Pca), after the early studies have resulted in favorable outcome and acceptable toxicity. Stereotactic MR-guided Adaptive Radiotherapy (SMART) has the advantages for markerless, MR guidance with daily adaptation and smaller PTV margins. We aimed to report our initial experience with SMART in localized Pca. Between 09/18-10/19, 35 consecutive patients with T1c-T3aN0M0 Pca were treated with MRidian MRLINAC (ViewRay, OH). Risk groups were low in 20%, intermediate in 57% and high in 23%. MR and CT simulation was done after 3 hours of fasting, fleet enema and 40 mins after 250 cc water. Isotropic PTV margin was 3 mm over CTV (prostate+/-seminal vesicles). Static IMRT plans to give 3625 cGy/5 fractions were studied. 26% received androgen ablation. All patients were treated every other day. Median follow up time was 7 (Range: 1-14) months. Plan adaptation was done in 74% of 175 fractions. The reasons for plan adaptation were target volume coverage in 38%, OAR violation in 26% and both in 32%. Overall treatment time was median 45 min (29-95 min, range). Acute GU toxicity was seen in 34% as Gr1 and in 11% as Gr2. GI toxicity was seen as Gr 1 in 6%. Alpha blocker was needed during treatment for urinary symptoms in 23% of patients. No grade 3 or higher acute or late toxicity was observed. Early PSA kinetics after treatment were positive as expected from SBRT. Only 1 high risk patient developed systemic metastasis and another patient developed biochemical failure. SMART is a tolerable and convenient markerless treatment method for localized Pca patients. Our early results support low toxicity with high rate of local control.

Reduction of cardiac dose using respiratory-gated MR-linac plans for gastro-esophageal junction cancer

Treatment of locally advanced adenocarcinoma of the gastroesophageal junction (GEJ) with chemoradiation may be associated with high rates of symptomatic cardiac toxicity. Large margins are typically required to ensure coverage of GEJ tumors with free-breathing volumetric modulated arc therapy (VMAT) radiotherapy. The purpose of this study is to determine whether treatment with tighter margins enabled by maximum-inhalation breath hold (MIBH)-gated intensity modulated radiation therapy (IMRT) on an integrated MRI-linear accelerator system (MR-linac) can decrease radiation doses to the heart and cardiac substructures. Ten patients with locally advanced GEJ adenocarcinoma underwent both free breathing 4-dimensional computed tomography (4DCT) and MIBH MRI simulation scans. MR-linac IMRT plans were created with a 3 mm clinical target volume (CTV) to planning target volume (PTV) isotropic margin and 4DCT VMAT plans were created with a 11, 13, and 9 mm CTV to PTV anisotropic margins in the left-right, cranial-caudal, and anterior-posterior directions according to GEJ-specific PTV expansion recommendations by Voncken et al. Prescription dose to PTV was 50.4 Gy in 28 fractions. Dosimetry to the heart and cardiac substructures was compared with paired t test; p < 0.05 was considered significant. Mean PTV on the MR-linac IMRT plans was significantly smaller compared to the 4DCT VMAT plans (689 cm3vs 1275 cm3, p < 0.01). Mean dose to the heart and all cardiac substructures was significantly lower in the MR-linac IMRT plans compared to the 4DCT VMAT plans: heart 20.9 Gy vs 27.8 Gy, left atrium 29.6 Gy vs 39.4 Gy, right atrium 20.5 Gy vs 25.6 Gy, left ventricle 21.6 Gy vs 29.6 Gy, and right ventricle 18.7 Gy vs 25.2 Gy (all p values <0.05). MIBH-gated MR-linac IMRT treatment of locally advanced GEJ adenocarcinoma can significantly decrease doses to the heart and cardiac substructures and this may translate to reduced rates of cardiac toxicity.

What is the dosimetric impact of isotropic vs anisotropic safety margins for delineation of the clinical target volume in breast brachytherapy?

PurposeThe purpose of the study was to report dosimetric differences for breast brachytherapy plans optimized for clinical target volume (CTV) generated using conventional isotropic expansion of tumor bed volume (TBV) and Groupe Européen de Curiethérapie–European Society for Radiotherapy and Oncology (GEC-ESTRO) recommendations to expand the TBV anisotropically to achieve a total safety margin of 2 cm (resection margin size + added safety margin). MethodsInstitutional records of 100 patients who underwent accelerated partial breast irradiation using multicatheter interstitial brachytherapy from May 2015 to March 2020 were reviewed retrospectively. Two sets of CT-based plans were made, one with 1-cm isotropic margins around the tumor bed (CTV_ISO) and the other with anisotropic margins (CTV_GEC). Plans were evaluated and compared using the American Brachytherapy Society and GEC-ESTRO guidelines. ResultsThe median TBV was 36.97 cc. The median margin widths were as follows: anterior 1.2, posterior 1.0, superior 1.0, inferior 0.9, medial 1.2, and lateral 1.2 cm. The mean tumor bed coverage index was 0.94; 0.93 [p.066], the CTV coverage index 0.86; 0.84 [p 0.001], the dose homogeneity index (DHI) 0.77; 0.75 [p < 0.001] and the conformity index 0.66; 0.64 [p < 0.001] in CTV_ISO and CTV_GEC plans, respectively. In smaller volume implants (TBV< 35 cc), the DHI was 0.76; 0.75 [p 0.008] and the conformity index was 0.66; 0.62 [p < 0.001], whereas in larger volumes >35 cc, the CTV coverage index was 0.86; 0.84 [p 0.003] and the DHI 0.78; 0.76 [p 0.001] in CTV_ISO and CTV_GEC plans, respectively. ConclusionsIn this cohort of patients who underwent accelerated partial breast irradiation, plans with anisotropic margins had lower conformity, the impact of which was predominantly seen in smaller implants. Rest of the dosimetric constraints were achieved in both the plans as per the American Brachytherapy Society and GEC-ESTRO guidelines.

Assessment of robustness of institutional applied clinical target volume (CTV) to planning target volume (PTV) margin in cervical cancer using biological models

The aim of this study is to investigate the robustness of our institutionally applied clinical target volume (CTV)-to-planning target volume (PTV) margins in cervical cancer patients in terms of an equivalent uniform dose (EUD) based on tumor control probability (TCP). We simulated target motion using 25 IMRT cervical cancer plans to demonstrate the effect of geometrical uncertainties on the EUD and TCP. The different components of the total geometrical uncertainties budget were estimated. The biological effects were compared by calculating the EUDs from the trial DVHs. The impact of geometric uncertainties was calculated as a percentage of the difference between 〖EUD〗_static and 〖EUD〗_motion, where the 〖EUD〗_static is the EUD calculated from the target DVHs and 〖EUD〗_motion is averaged, over a 1000 calculated EUDs for each of the analyzed IMRT treatment plans. The multivariate nonlinear regression was used to find the predicted difference between the static and motion EUD. The estimate of the systematic and random motion errors were Σ_(total(SI,LR,AP)) (mm)=(2.6; 2.5; 1.8) and σ_(total(SI,LR,AP)) (mm)=(3.4; 1.4; 3.4). For average 〈EUD〉_motion=44.3 Gy (over 25 patients) we have found a TCP decrease of about 1%, %(ΔTCP)≈1% for predefined PTV margin. According to the calculated EUD motion-distributions, for particular patients, the CTV does receive the prescribed EUD of 45 Gy. The predicted difference in EUD showed that our isotropic margin of 10 mm is large enough to absorb geometric uncertainties and ensure dose coverage of the moving CTV in the cervical cancer patients.

Impact of Inter-fractional Anatomical Changes on Dose Distributions in Passive Carbon-Ion Radiotherapy for Prostate Cancer: Comparison of Vertical and Horizontal Fields.

Purpose: We quantified the inter-fractional changes associated with passive carbon-ion radiotherapy using vertical and horizontal beam fields for prostate cancer.Methods: In total, 118 treatment-room computed tomography (TRCT) image sets were acquired from 10 patients. Vertical (anterior–posterior) and horizontal (left–right) fields were generated on the planning target volume identified by treatment planning CT. The dose distribution for each field was recalculated on each TRCT image set at the bone-matching position and evaluated using the dose–volume parameters for the prostate and rectum V95 values. To confirm adequate margins, we generated vertical and horizontal fields with 0-, 2-, 4-, and 6-mm isotropic margins from the prostate and recalculated the dose distributions on all TRCT image sets. Sigmoid functions were fitted to a plot of acceptable ratios (that is, when prostate V95 > 98%) vs. the isotropic margin size to identify the margin at which this ratio was achieved in 95% of patients with a vertical or horizontal field.Results: The prostate V95 values (mean ± standard deviation) were 99.89 ± 0.62% and 99.99 ± 0.00% with vertical and horizontal fields, respectively; this difference was not statistically significant (p = 0.067). The rectum V95 values were 1.93 ± 1.25 and 1.88 ± 0.96 ml with vertical and horizontal fields, respectively; the difference was not statistically significant (p = 0.432). The estimated adequate margins were 2.2 and 3.0 mm for vertical and horizontal fields, respectively.Conclusions: Although there is no significant difference, horizontal fields offer higher reproducibility for prostate dosing than vertical fields in our clinical setting, and 3.0 mm was found to be an adequate margin for inter-fractional changes.

Reduced Margin Stereotactic Body Radiation Therapy for Early Stage Non-Small Cell Lung Cancers.

PurposeOur study reports the clinical outcomes of patients treated with 5-mm isotropic margin, fiducial-guided stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC). We also sought to assess the effect of histological subtype on local control.MethodsWe retrospectively reviewed the charts of all patients treated with SBRT for NSCLC between 2007 and 2017 at our institution. All patients who had implanted fiducial markers, planning target volume (PTV) margins of 5 mm or less, early stage disease (T1-T2, N0), and at least one follow-up CT were included in this analysis. Estimates of local control were generated using the Kaplan-Meier method, and differences between survival curves were assessed using the log-rank test.ResultsA total of 152 patients met the inclusion criteria for this analysis, with a median follow-up of 27.9 months. Patients received 54 Gy in three fractions for peripheral tumors and 48-52.5 Gy in four to five fractions for central tumors. NSCLC histology was adenocarcinoma in 69 (45.4%) cases, squamous cell carcinoma in 65 (42.8%) cases, and other or non-subtyped in 18 (11.8%) cases. Across the entire cohort, the two-year estimate of local control was 95.1%. When histology was considered, the two-year estimate of local control among patients with adenocarcinoma was 95.6% as compared with 85.0% for patients with other subtypes (p=0.044).ConclusionsFiducial-guided, isotropic 5-mm PTV margin for thoracic SBRT did not compromise local control compared with historical standards. In this series, patients with adenocarcinoma experienced improved local control compared with squamous cell carcinoma.

Target miss using PTV-based IMRT compared to robust optimization via coverage probability concept in prostate cancer

Purpose: Cure- and toxicity rates of prostate IGRT can both be affected by ill-chosen planning target volume (PTV) margins. For dose-escalated prostate radiotherapy, we studied the potential for organ at risk (OAR) sparing and compensation of prostate motion with robust plan optimization using the coverage probability (CovP) concept compared to conventional PTV-based IMRT.Material and methods: We evaluated plan quality of CovP-plans for 27 intermediate risk prostate cancer patients treated in a prospective study (78 Gy/39 fractions). Clinical target volume (CTV) and OARs were contoured on three separate CTs to capture movement and deformation. To define the internal target volume (ITV), the union of CTV1-3 was encompassed by an isotropic margin of 7 mm for the planning process. CovP-dose distribution is optimized considering weight factors for IMRT constraints derived from probabilities of systematic organ displacement in the three CTs. CovP-dose volume histograms (DVHs) were compared with additionally calculated conventional PTV-based IMRT plans. PTV-based IMRT was planned on one-single CT with an isotropically expanded CTV to generate the PTV (i.e., CTV1 + 7mm) and was evaluated on the two other CTs.Results: The CovP-concept showed higher robustness in target volume coverage. Target miss was frequently observed with PTV-based IMRT, resulting in cold spots until 70 Gy with the CovP-concept. The target dose at 74 Gy was comparable, while further the dose–escalation (75–78 Gy) was improved with PTV-based IMRT. However, dose–escalation with PTV-based IMRT was associated with increased OAR-doses, especially in high-dose areas.Conclusions: Probabilistic dose-escalated IMRT was feasible in this prospective study. Comparison of the CovP-concept with PTV-based IMRT revealed superiority with regard to target-coverage and sparing of OARs. The CovP-concept implements a robust plan optimization strategy for organ deformation and motions and could, therefore, serve as a less demanding compromise on the way to adaptive IGRT avoiding daily time-consuming re-planning. SUMMARYWe evaluated the robustness of coverage probability (CovP)-based IMRT plans within a prospective study for prostate cancer radiotherapy. The treatment plans were compared with newly calculated conventional PTV-based IMRT plans. We were able to show that CovP led to a clearly more robust target coverage by avoiding hot spots at OARs compared to conventional PTV-based IMRT. In addition, negative consequences of an inflated PTV can be ameliorated by a more relaxed CovP-based dose prescription.