Planning Target Volume Expansion Research Articles

Abstract P4-12-21: Implementing a real-time magnetic resonance imaging guided accelerated partial breast irradiation program

Abstract Motivation: Clinical evidence has shown that accelerated partial breast irradiation (APBI) for early stage breast cancer patients result in local recurrence control rates and cosmetic outcomes comparable to whole breast irradiation. Approaches to APBI include brachytherapy, intraoperative radiation therapy and external beam radiation therapy (EBRT). EBRT is the least invasive approach, most widely available, and does not require additional training. For EBRT APBI, based on NSABP B39/RTOG 0413 protocol, the clinical target volume (CTV) is generated by applying a 1.5 cm margin to the lumpectomy bed and the planning target volume (PTV) is generated by applying an additional 1 cm margin from the CTV to account for set up uncertainties.Real-time magnetic resonance imaging guided radiation therapy (MRgRT) allow for reduced treatment margins by decreasing treatment setup uncertainties. In this work, we share our experience in implementing a MRI guided accelerated partial breast irradiation (MRgAPBI) program into a new clinic with a linear accelerator capable of real-time MRI imaging. Methods: We have surveyed institutions in which rely on MRI guidance for APBI treatments through a comprehensive literature review and onsite visits. These visits included our radiation therapists, physicists, and radiation oncologists. There are two main components in implementing a new radiotherapy program: 1) patient simulation and immobilization techniques, and 2) treatment planning and delivery techniques. These techniques were studied and modified for our clinical workflow. Results: Literature review revealed a single institution report addressing their MRgAPBI experience. For immobilization, we adopted two techniques observed during two site visits. However, these techniques were later modified to allow for patient customization. For small breasted patients, a foam tube placed along the sternum is used and for large breasted patients, we employed custom made acrylic brackets placed superior to the shoulders which are then built into the patient's immobilization cradle for individualized set up. For patient comfort, the contralateral arm is placed down along the patient’s side, whereas the ipsilateral arm is moved up away from the radiation field. This also allows for lateral clearance for beam selection. For treatment planning, consensus on optimal margin for expansion from the lumpectomy bed is of utmost importance. A single institution MRgAPBI report described a 1 cm expansion from the lumpectomy bed to PTV while NSABP B39 indicated a 2.5 cm expansion. This reduction in margin was justified by the utilization of real-time MRgRT. We have come to consensus to use a 1.5 cm expansion around the lumpectomy cavity, which accounts for the CTV expansion per NSABP B39 and to forgo the PTV expansion given the minimal setup uncertainty with online MRgRT. Our initial experience showed significant changes in the lumpectomy cavity shape and volume when the gap between patient simulation and the start of treatment exceeded a week. We have thus reduced the time between simulation and treatment to 1 week to address this issue. Conclusion: Implementing a new MRgAPBI program requires a comprehensive evaluation of available resources and published reports, as well as, team visits to expert MRgAPBI centers. Both immobilization techniques and lumpectomy margin expansions for treatment planning should be well thought of prior to starting a similar program. In our experience, time between simulation and treatment of 1 week showed minimal changes in the shape and size of the planning volume. Additional verification will need to be conducted within a prospective setting and larger cohort. In order to setup a successful program, teamwork is essential between all groups including radiation therapists, dosimetrists, physicists, and radiation oncologists. Citation Format: Eenas A. Omari, Jennifer Gambla, Hahn P. Mai, Muaiad Kittaneh, Tarita O. Thomas, Raymond B. Wynn, Anil Sethi, William Small Jr, Tamer Refaat. Implementing a real-time magnetic resonance imaging guided accelerated partial breast irradiation program [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-21.

Clinical outcomes for larynx patients with cancer treated with refinement of high-dose radiation treatment volumes.

To evaluate disease control, toxicities, and dose to dysphagia/aspiration risk structures (DARS) using a direct gross tumor volume (GTV70Gy ) to planning target volume expansion (dPTV70Gy ) for patients with squamous cell carcinoma of the larynx (LSCC). A retrospective review was performed on patients with LSCC treated between 2003 and 2018. Clinical outcomes, toxicities, and dosimetric data were analyzed. Seventy-three patients were identified. Overall survival at 5-years was 57.8%. Five-year local and regional control was 79.8% and 88.2%, respectively. Distant metastatic-only failure was 2.7%. Eighty percent of failures were 95% contained within the dPTV70Gy . Mean dose and the volume of DARS receiving 70 Gy was significantly lower for dPTV70Gy compared to a consensus-defined PTV70Gy . Judicious reduction in high-dose target volumes can preserve high tumor control rates while reducing dose to normal surrounding structures underscoring the potential benefit of this approach in enabling local therapy intensification to improve locoregional control.

Dosimetric Factors Related to Radiation Necrosis After 5-Fraction Radiosurgery for Patients With Resected Brain Metastases

PurposeStereotactic radiosurgery (SRS) is increasingly used in the management of patients with resected brain metastases (rBMs). A significant complication of this therapy can be radiation necrosis (RN). Despite radiation therapy dose de-escalation and the delivery of several rather than a single dose fraction, rates of RN after SRS for rBMs remain high. We evaluated the dosimetric parameters associated with radiographic RN for rBMs. Methods and MaterialsFrom 2008 to 2016, 55 rBMs at a single institution that were treated postoperatively with 5-fraction linear accelerator–based SRS (25-35 Gy) with minimum 3 months follow-up were evaluated. For each lesion, variables recorded included radiation therapy dose to normal brain, location and magnitude of hotspots, clinical target volume (CTV), and margin size. Hotspot location was stratified as within the tumor bed alone (CTV) or within the planning target volume (PTV) expansion margin volume (PTV minus CTV). Cumulative incidence with competing risks was used to estimate rates of RN and local recurrence. Optimal cut-points predicting for RN for hotspot magnitude based on location were identified via maximization of the log-rank test statistic. ResultsMedian age for all patients was 58.5 years. For all targets, the median CTV was 17.53 cm3, the median expansion margin to PTV was 2 mm, and the median max hotspot was 111%. At 1 year, cumulative incidence of radiographic RN was 18.2%. Univariate analysis showed that max hotspots with a hazard ratio of 3.28 (P = .045), hotspots within the PTV expansion margin with relative magnitudes of 105%, 110%, and 111%, and an absolute dose of 33.5 Gy predicted for RN (P = .029, P = .04, P = .038, and P = .0488, respectively), but hotspots within the CTV did not. ConclusionsTo our knowledge, this is the first study that investigated dosimetric factors that predict for RN after 5-fraction hypofractionated SRS for rBM. Hotspot location and magnitude appear important for predicting RN risk, thus these parameters should be carefully considered during treatment planning.

Real-time Magnetic Resonance-guided Liver Stereotactic Body Radiation Therapy: An Institutional Report Using a Magnetic Resonance-Linac System.

BackgroundStereotactic body radiation therapy (SBRT) is a proven and effective modality for treatment of hepatic primary and metastatic tumors. However, these lesions are challenging for planning and treatment execution due to natural anatomic changes associated with respiration. Magnetic resonance imaging (MRI) offers superior soft tissue contrast resolution and the ability for real-time image-guided treatment delivery and lesion tracking.ObjectiveTo evaluate the plan quality, treatment delivery, and tumor response of a set of liver SBRT cancer treatments delivered with magnetic resonance (MR)-guided radiotherapy on a MR-linear accelerator (MR-linac).MethodsTreatment data from 29 consecutive patients treated with SBRT were reviewed. All treatments were performed using a step and shoot technique to one or more liver lesions on an MR-linac platform. Patients received 45 to 50 Gy prescribed to at least 95% of the planning target volume (PTV) in five fractions except for two patients who received 27-30 Gy in three fractions. Computed tomography and MRI simulation were performed in the supine position prior to treatment in the free-breathing, end exhalation, and end inhalation breath-hold positions to determine patient tolerability and potential dosimetric advantages of each technique. Immobilization consisted of using anterior and posterior torso MRI receive coils embedded in a medium-sized vacuum cushion. Gating was performed using sagittal cine images acquired at 4 frames/second. Gating boundaries were defined in the three major axes to be 0.3 to 0.5 cm. An overlapping region of interest, defined as the percentage volume allowed outside the boundary for beam-on to occur, was set between 1 and 10%. The contoured target was assigned a 5-mm PTV expansion. Organs at risk constraints adopted by the American Association of Physicists in Medicine Task Group 101 were used during optimization.ResultsTwenty-nine patients, with a total of 34 lesions, successfully completed the prescribed treatment with minimal treatment breaks or delays. Twenty-one patients were treated at end-exhale, and six were treated at end-inhale. Two patients were treated using a free-breathing technique due to poor compliance with breath-hold instructions. The reported mean liver dose was 5.56 Gy (1.39 - 10.43; STD 2.85) and the reported mean liver volume receiving the prescribed threshold dose was 103.1 cm3 (2.9 - 236.6; STD 75.2). Follow-up imaging at one to 12 months post treatment confirmed either stable or decreased size of treated lesions in all but one patient. Toxicities were mild and included nausea/vomiting, abdominal pain and one case of bloody diarrhea. Four patients died due to complications from liver cirrhosis unrelated to radiation effect.ConclusionSBRT treatment using a gated technique on an MR-linac has been successfully demonstrated. Potential benefits of this modality include decreased liver dose leading to decreased toxicities. Further studies to identify the benefits and risks associated with MR-guided SBRT are necessary.

Increased Local Recurrence Rates in Patients Receiving Stereotactic Body Radiotherapy for Non-Small Cell Lung Cancer When Using Phase Based Respiratory Gating

Motion management is an integral component of lung stereotactic body radiotherapy (SBRT) due to target motion during respiration. Respiratory gating is a strategy that decreases the treated volume by radiating the target only in specific phases of the breathing cycle. There are few data on the clinical impact of respiratory gating on disease control in SBRT. In this study we investigated the effect of phase based respiratory gating on local and regional recurrence in non-small cell lung cancer (NSCLC) patients receiving SBRT. We performed a retrospective review of patients treated with lung SBRT (who received at least a biological effective dose of > 100 Gray) for NSCLC from 2011-2017. All patients were simulated using a 4D CT technique and respiratory gating was used at physician discretion, typically if tumor excursion was greater than 1 cm. Phase based gating was performed using a non-invasive, video-based system. An internal target volume was created for all lesions, with a circumferential planning target volume expansion of 0.5 cm. Patients were aligned via cone beam CT imaging prior to and during treatment. Variables associated with local and regional recurrence were assessed via univariate, Cox regression, and Kaplan-Meier analyses. 190 treated pulmonary lesions in 160 patients were analyzed. 39% of patients were male. Mean age at SBRT was 73 years and median follow up time was 23 months. 50% of lesions were adenocarcinomas, 28% squamous cell carcinomas, and 18% were unbiopsied nodules. 61% of lesions were in the upper lobes and 39% in the lower lobes. 39.5% of treated lesions employed respiratory gating. There were no differences in the use of gating during SBRT with respect to lobe, diagnosis, tumor size, or age. Use of gating was found to be significantly associated with a higher risk of local recurrence on univariate analysis (p=0.001). No other variables analyzed were found to have a significant effect on local recurrence rate. Local control rate at two years was significantly different between non-gated and gated patients in Kaplan-Meier log-rank analysis (97% versus 88.4%, respectively, p =0.013). On multivariate Cox regression analysis with all covariates factored, only gating had a significant effect on local recurrence hazard rate (p=0.018). No variables assessed were associated with an increased risk of regional recurrence. In this retrospective study local control was decreased by 8.6% at two years in patients who were treated using phase based respiratory gating. The factors underlying this difference are unclear, but may include patient selection, challenges in implementation of the technology, or other clinical or technical variables; caution should be exercised when using phase based gating as the potential for compromised tumor control exists.

Reducing radiotherapy target volume expansion for patients with HPV-associated oropharyngeal cancer

PurposeTo evaluate clinical outcomes and patterns of failure using a direct gross tumor volume to planning target volume expansion in patients with p16-positive oropharyngeal squamous cell carcinoma. Methods and materialsWe performed a retrospective review of patients with p16-positive oropharyngeal squamous cell carcinomas treated between 2002 and 2017 with primary radiotherapy with or without concurrent systemic therapy. Patient and disease characteristics associated with disease control and clinical outcomes were analyzed by Cox proportional hazards regression and Kaplan-Meier analyses. Imaging at the time of first failure was used to categorize failure patterns. ResultsWe identified 134 patients with a median follow-up of 56.2 months (range 8.2–160.2 months). Local and regional control at 5 years was 91.5% (95% CI: 86.8–96.4%), and 90.8% (95% CI: 85.6–96.2%), respectively. Of the 14 locoregional failures, there were 10 in-field (Type A), 3 marginal (Type B), and 1 geographic (Type E). Age >70 years (HR 5.42; 95% CI: 1.87–15.68) and T4 versus T1-3 (HR 4.09; 95% CI: 1.01–2.65) were associated with increased rates of locoregional failure on multivariate analysis. The rate of gastrostomy tube retention at one year was 6.0% (range 2.8–12.7%). ConclusionsManagement of patients with p16-positive oropharyngeal squamous cell carcinoma using definitive radiotherapy and a high-dose planning target volume created without a gross tumor volume to clinical tumor volume expansion resulted in high locoregional control with the vast majority of failures occurring within the high-dose field. These data warrant prospective evaluation of this technique as a therapy de-intensification approach.

Fiducial markers in prostate cancer image-guided radiotherapy.

Background: Image-guided radiotherapy (IGRT) is recommended to reduce the risk of geometrical miss when modern radiotherapy technologies with high grades of conformity are used. The purpose of this study was to evaluate the efficacy of fiducial markers (FMs) for electronic portal imaging in prostate cancer radiotherapy in term of evaluating the complications associated with FMs implantation, quantifying inter-fraction prostate motion, and determination of optimal planning target volume (PTV) margins. Methods: In this single institution, prospective, consecutive study, 27 patients underwent implantation of three-gold seed FMs into the prostate gland before prostate radiotherapy. Prior to computed tomography planning, all patients were asked to report any complication associated with FMs implantation that have experienced to date. Daily pre-treatment electronic portal images were captured, and prostate position errors were corrected if they were greater than 2 mm along three translational directions. Optimal PTV expansions were computed using van Herk formula [PTV-margin= 2.5Σ + 0.7σ]. Results: FMs implantation was successful with an acceptable toxicity profile in all patients. Without IGRT, margins of 5.4 mm, 5.8 mm and 5.5 mm, in vertical, longitudinal and lateral directions, respectively, are needed for a 95% confidence level of complete clinical target volume (CTV) coverage in each treatment session. The PTV margins of 3.0 mm, 3.3 mm and 4.0 mm in corresponding directions were calculated when FMs based electronic portal imaging was applied. Conclusion: FMs based electronic portal imaging is an effective tool for prostate cancer IGRT.

Potential benefit of MRI-guided IMRT for flank irradiation in pediatric patients with Wilms’ tumor

Purpose/Objective: Flank irradiation for Wilms' tumor (WT) is currently performed at our institute using a cone-beam computed tomography-guided volumetric modulated arc (VMATCBCT) workflow. By adding real-time magnetic resonance imaging (MRI) guidance to the treatment, safety margins could be reduced. The study purpose was to quantify the potential reduction of the planning target volume (PTV) margin and its dosimetric impact when using an MRI-guided intensity modulated radiation therapy (IMRTMRI) workflow compared to the VMATCBCT workflow.Material/Methods: 4D-CT, MRI and CBCT scans acquired during preparation and treatment of 15 patients, were used to estimate both geometric, motion and patient set-up systematic (∑) and random (σ) errors for VMATCBCT and IMRTMRI workflows. The mean PTV (PTVmean) expansion was calculated using the van Herk formula. Treatment plans were generated using five margin scenarios (PTVmean ± 0, 1 and 2 mm). Furthermore, the IMRTMRI plans were optimized with a 1.5T transverse magnetic field turned-on to realistically model an MRI-guided treatment. Plans were evaluated using dose-volume statistics (p<.01, Wilcoxon).Results: Analysis of ∑ and σ errors resulted in a PTVmean of 5 mm for the VMATCBCT and 3 mm for the IMRTMRI workflows in each orthogonal direction. Target coverage was unaffected by the margin decrease with a mean V95%=100% for all margin scenarios. For the PTVmean, an average reduction of the mean dose to the organs at risk (OARs) was achieved with IMRTMRI compared to VMATCBCT: 3.4 ± 2.4% (p<.01) for the kidney, 3.4 ± 2.1% (p<.01) for the liver, 2.8 ± 3.0% (p<.01) for the spleen and 4.9 ± 3.8% (p<.01) for the pancreas, respectively.Conclusions: Imaging data in children with WT demonstrated that the PTV margin could be reduced isotropically down to 2 mm when using the IMRTMRI compared to the VMATCBCT workflow. The former results in a dose reduction to the OARs while maintaining target coverage.

Outcomes After Hypofractionated Dose-Escalation using a Simultaneous Integrated Boost Technique for Treatment of Spine Metastases Not Amenable to Stereotactic Radiosurgery

PurposeSpine stereotactic radiosurgery delivers an ablative dose of radiation therapy (RT) with high conformity relative to standard fractionated RT. This technique is suboptimal for extended targets (>3 vertebral levels) owing to treatment alignment concerns or for patients with marked epidural extension. In these patients, we hypothesized that use of hypofractionated intensity modulated RT/volumetric modulated arc therapy to dose escalate the gross tumor volume (GTV) to 40 Gy as a spinal simultaneous integrated boost (SSIB) would allow for durable local control and palliation. Methods and MaterialsWe retrospectively analyzed 15 separate spinal sites (12 patients) that were treated with the SSIB technique between 2012 and 2016. The GTV and clinical target volume were prescribed at 40 Gy and 30 Gy, respectively, in 10 fractions. The spinal cord was allowed a maximum point dose of 34 Gy. The GTV was defined as gross tumor. The clinical target volume encompassed the GTV in addition to the involved vertebral bodies, at-risk paraspinal space, and spinal canal, followed by a planning target volume expansion of 3 to 5 mm. ResultsThe median follow-up for patients in our cohort was 17 months. At 1 year, local control was 93%, and overall survival was 58%, with a median time to death after treatment of 7 months. No grade ≥2 neurologic toxicities were reported for any of the patients. Nine of 12 patients had pain at presentation, of which 7 patients (78%) reported improvement and/or complete resolution of their pain after treatment. ConclusionsOur early experience using a dose of 40 Gy to the GTV delivered via an SSIB technique, in lieu of spine stereotactic radiation surgery but more aggressive than conventional palliative doses, provides durable local control and pain relief. This technique may allow for improved local control and palliation in patients with radioresistant disease compared with conventional 3-dimensional conformal fractionated RT.

Consensus Guidelines for Target Volume Definition of the Sacrum in Spinal Stereotactic Body Radiation Therapy (SBRT)

To develop consensus contouring guidelines for spinal stereotactic body radiation therapy (SBRT) for metastatic disease to the sacrum to improve uniformity in clinical target volume (CTV) delineation. Nine radiation oncologists with spinal stereotactic radiotherapy expertise representing 9 international centres in 3 countries independently contoured gross tumor volume (GTV), CTV and neural elements (cauda equina, thecal sac or sacral canal) for 10 representative clinical scenarios in metastatic disease to the sacrum. Contours were imported into an in-house software program, and agreement between physicians calculated with an expectation minimization algorithm using simultaneous truth and performance level estimation (STAPLE) and with kappa statistics (<0, poor agreement; 0.01-0.20, slight agreement; 0.21-0.40, fair agreement; 0.41-0.60, moderate agreement; 0.61-0.80, substantial agreement; 0.81-1.00, almost perfect agreement). Optimized confidence level consensus contours were obtained using a voxel-wise maximum likelihood approach. Clinicians also completed an 18-question survey about sacral metastatic disease SBRT practice including dose/fractionation schedule, margin expansion for GTV to CTV and CTV to planning target volume (PTV), the practice of contouring the sacral plexus and/or peripheral nerve roots and acceptable dose constraints for neural elements and small/large bowel. The mean STAPLE agreement sensitivity and specificity was 0.73 (range, 0.59-0.86) and 1.00 respectively for GTV and 0.59 (range, 0.47-0.69) and 1.00, respectively for CTV. The mean kappa agreement was 0.76 (range, 0.60-0.89) for GTV and 0.60 (range, 0.45-0.72) for CTV (P<.001 for GTV and CTV in all cases). Different dose/fractionation schedules used included 16-24 Gy/1 fraction, 24 Gy/2 fractions, 24-27 Gy/3 fractions, 30-36 Gy/4 fractions and 35 Gy/5 fractions, primary histology of the tumor was a factor in certain cases when choosing a schedule. Six experts applied an anatomic approach to the CTV, in some cases adding an extra margin for soft tissue extension/extra-osseous disease. Median PTV expansion was 1 mm (range, 0 – 3 mm). Six experts contoured the thecal sac as a surrogate for the cauda equina. In the majority of cases the sacral plexus and peripheral nerves were contoured however the lack of consensus contouring guidelines and low rates of clinical plexopathy observed in practice were reasons why contouring these critical normal structures wasn’t universal practice. There was substantial agreement for GTV and moderate agreement for CTV contours with the majority of international experts applying an anatomic approach when contouring the CTV. Final consensus guidelines will be demonstrated in illustrations at the meeting.

A method for optimizing planning target volume margins for patients receiving lung stereotactic body radiotherapy

Lung stereotactic-body radiotherapy (SBRT) places additional requirements on targeting accuracy over standard approaches. In treatment planning, a tumour volume is geometrically expanded and the resulting planning target volume (PTV) is covered with the prescribed dose. This ensures full dose delivery despite various uncertainties encountered during treatment.We developed a retrospective technique for optimizing the PTV expansion for a patient population. The method relies on deformable image registration (DIR) of the planning CT to a treatment cone-beam CT (CBCT). The resulting transformation is used to map the planned target onto the treatment geometry, allowing the computation of the achieved target/PTV overlap.Basic validation of the method was performed using an anthropomorphic respiratory motion phantom. A self-validation technique was also implemented to allow estimation of the DIR error for the data being analyzed. Our workflow was used to retrospectively optimize PTV margin for 25 patients treated over 93 fractions. Targets for these patients were contoured on 4D CT images. SBRT delivery followed CBCT acquisition and a couch correction. A post-treatment CBCT was also acquired in some cases.Our basic validation demonstrated that the DIR-based technique is capable of transforming target volumes from planning CTs to treatment CBCTs with sub-mm accuracy. Our clinical analysis showed that the minimum percentages of target volumes covered for 3, 4, and 5 mm PTV margins were 92.1, 97.6, and 99.2, respectively. Analyzing data acquired before and just after treatment demonstrated that margins exceeding 5 mm did not significantly improve coverage. Finally, a 5 mm PTV margin achieved ⩾95% target volume coverage with ⩾95% probability.Our technique is accurate, automated, self-validating, and incorporates complex ITV shapes/deformations to allow PTV margin optimization. The analysis of clinical data indicates a 5 mm PTV margin is optimal for our process. This approach is generalizable to other disease sites and treatment strategies.

Anisotropic Bladder Planning Target Volume in Bladder Radiation Therapy

PurposeThis study aimed to investigate 3 planning target volume (PTV) margin expansions and determine the most appropriate volume to be used in bladder preservation therapy when using daily cone beam computed tomography (CBCT). We aimed to establish whether a smaller PTV expansion is feasible without risking geographical miss. Methods and materialsThe study included patients with bladder cancer who were treated with a hypofractionated course of radiation therapy delivered with intensity modulated radiation therapy. The clinical target volume (CTV) was the whole empty bladder, and the PTV consisted of a 1.5-cm margin around the bladder (PTV1.5 cm). Patients underwent daily CBCT imaging before treatment to assess the bladder volume and ensure accurate positioning. We investigated 2 additional smaller PTV margin expansions to determine the most appropriate volume to be used with CBCT as a daily image guided radiation therapy modality. These margins were created retrospectively on every CBCT. The first additional volume was a uniform PTV margin of the surrounding 1 cm (PTV1 cm). When considering that the majority of the internal bladder movement was due to the variation in filling that occurs in the superior and anterior directions, a second volume of an anisotropic PTV margin with a 1.5-cm superior/anterior and 1 cm in other directions (PTV1/1.5 cm) was created. We recorded the frequency and measured the volume of bladder falling out of each PTV based on the daily CBCT. ResultsFor the purpose of this study, we considered an arbitrary 5 cm3 of CTV falling out of the designated PTV as a clinically significant volumetric miss. The frequency of such a miss when applying the uniform PTV1 cm was 1%. However, when applying the uniform PTV1.5 cm and anisotropic PTV1/1.5 cm margins, the frequency was 0.5% and 0.5%, respectively. ConclusionsThe anisotropic PTV expansion of 1.5 cm superiorly and anteriorly and 1 cm in all other directions around the bladder (CTV) provides a safe PTV approach when daily CBCT imaging is used to localize an empty bladder.

(OA22) Inter-Fractional Motion in Patients With Intact Cervical Cancer Treated on a MRI Guided External Beam Radiation Therapy System

Treatment verification has improved significantly over the past decades, now with the ability to have on-board MRI guidance. MRI provides superior soft tissue contrast compared to CT-based imaging modalities and provides better delineation of pelvic organs and gross tumor volumes (GTV) for those with cervical cancer. Consensus contouring guidelines for intensity modulated radiation therapy (IMRT) for cervical cancer advise including the whole uterus in the target volume and adding large planning target volume (PTV) margins to account for inter- and intra-fractional uncertainties. The primary objectives of our analysis was to assess the inter-fractional GTV motion for those with an intact cervix using on-board, daily MRI and to assess the relationship between bladder and rectal volumes and GTV motion. We analyzed 125 daily set-up MRI’s from five patients with intact cervical cancer who received MRI-guided pelvic IMRT at our institution between September 2016 and October 2017. The GTV, bladder, uterus, and rectum were contoured on all 125 MRI’s, which included 25 daily set-up MRI’s for each patient. The daily set-up MRI was registered with the planning MRI to assess organ motion. Tumor motion was assessed using GTV centroid displacements baselined to the planning MRI. Tumor volume and organ volumes were determined for each fraction. Then, a linear regression analysis was utilized to evaluate the relationship between rectal and bladder volumes and GTV motion. Patients were advised to have comfortable bladder filling for treatment. The initial GTV’s ranged in size from 31.9 cc to 119.5 cc. All GTV’s decreased in size during the course of external beam radiation, ranging from 34.0% to 85.2% of the initial tumor volumes on the final day of treatment. The ranges of daily centroid GTV displacement for all patients were from 0.08 cm to 2.23 cm, and the median GTV displacement for each patient was 0.69 cm to 1.04 cm. On linear regression analysis, 4 out of 5 patients demonstrated a strong relationship between rectal volume and GTV displacement with 26.4% of these displacements larger than 1 cm. Rectal volumes had the strongest impact on anterior-posterior GTV motion. Rectal volume appeared to better correlate with GTV displacement than bladder volume. However, for large tumors (>75 cc), tumor shrinkage during the course of radiation therapy seemed to have the most significant impact on GTV displacement. GTV shrinkage for large tumors strongly correlated with inferior GTV shifts, which were up to 1.4 cm in magnitude. Inter-fractional target motion is considerable and is affected by a variety of factors, including target volume changes, rectal volume, and, to a lesser degree, bladder volume. Our data suggests GTV shrinkage for large tumors has the greatest impact on GTV displacement. Inclusion of the whole uterus within the target volume and large CTV to PTV expansions remain standard practice. However, since the GTV is easily visible on daily MR imaging, one could think that eventually the target volume may exclude the uterine fundus and may also allow for decreased PTV margins with the ultimate goal of decreasing treatment toxicity.

Patterns and correlates of treatment failure in relation to isodose distribution in non-small cell lung cancer: An analysis of 1522 patients in the modern era

Background and purposeTo examine the relationship between radiation dose and tumor control in limited stage non-small cell lung cancer (NSCLC). Materials and methodsWe searched a database of 1552 patients who received radiation therapy for non-metastatic NSCLC between 2000 and 2016. The primary endpoint was freedom from in-field failure. ResultsIncreasing BED correlated with decreasing estimated gross tumor volume–planning target volume expansion, and on multivariable analysis increasing BED was associated with an increased chance of field-edge failures (hazard ratio [HR] 1.032, 95% confidence interval [CI] 1.004–1.062, P = 0.027). Increasing BED also correlated with improved freedom from in-field failure on multivariable analysis (HR 0.978, 95% CI 0.964–0.993, P = 0.003), with the dose–response curve showing a sigmoidal relationship between increasing BED and freedom from in-field failure. ConclusionIn this large study of patients treated in the modern era with varying dose fractionation regimens, higher BED was associated with improved freedom from in-field failure, and that this relationship appeared to be consistent with the classically described sigmoid shape. We also found that increased BED was associated with higher field-edge failures, implying that margin size may need to be further studied in patients receiving ablative regimens of radiation.

Fiducial Markers are Necessary for Accurate Delivery of Liver SBRT

We standardly use fiducial markers for target localization when administering liver stereotactic body radiation therapy (SBRT). However, there are few data demonstrating the impact of matching to fiducials on accuracy of liver SBRT delivery. Given the risks of percutaneous placement of fiducials, the aim of our study was to evaluate the benefit of fiducial-based SBRT and to potentially define a subset of patients that can be treated without fiducial markers. Nineteen metastatic (n = 15) and primary (n = 4) liver tumors were treated with SBRT. Doses ranged from 30-54 Gy in 3-5 fractions, and 75 individual fractions were delivered in total. Target localization at the time of treatment was performed using fiducial markers on cone beam computed tomography (CBCT). To assess the difference between fiducial-based and non-fiducial based set-up, each CBCT was then retrospectively realigned to best match the liver edge. The fiducial marker position was considered the gold standard. Shifts from the fiducial to liver edge alignment were recorded and an absolute Cartesian shift was calculated. To predict the dosimetric impact of these position errors, an artificial neural network was used to model the dose in the vicinity of the tumor. When aligning to the liver edge, the mean absolute Cartesian shift from fiducial alignment was 4.5 mm (0.73 – 13.3 mm). The lateral, longitudinal, and vertical shifts, were randomly distributed with mean values of 0.19 mm (-5.9 – 8.2 mm), -0.23 mm (-10.5 – 8.8 mm), and 0.43 mm (-9.0 – 8.4 mm), respectively. Thirty-three percent of fractions were found to have an absolute shift greater than 5 mm [our standard planning target volume (PTV) expansion] and 63% of patients had at least one absolute shift greater than 5 mm. In the neural network dose model, a 5 mm shift was associated with a dose reduction of 18.5% + 2.5%. The maximum shift seen was 13.3 mm which was associated with a projected target dose reduction of 45.0% + 5.6%. There were no tumor factors (including tumor size, distance from liver edge to the tumor, and distance from the tumor to the liver dome) that had a statistically significant correlation with worse alignment when matching to the liver edge without fiducials. Our findings demonstrate that treatment set-up without fiducial markers in liver SBRT leads to a mean positional error of 4.5 mm as compared to fiducial-based set-up. In one third of treatments, this variation was greater than our standard PTV expansion and would result in a substantial decrease in delivered dose. We were unable to define a subset of patients where fiducial markers may not be necessary. While these data suggest that with current technology, fiducial markers are necessary for the accurate delivery of liver SBRT; further work is needed to improve on-board imaging and localization techniques to allow for fiducial-less liver SBRT.

Measuring Radiotherapy Setup Errors in IMRT Treated Head and Neck Cancer Patients Requiring Bilateral Neck Irradiation, NCI-Egypt Experience

Objective: We aim to quantify the magnitude of setup errors in intensity-modulated radiotherapy (IMRT) treated Head and Neck cancer patients and recommend appropriate PTV margin. Methods: 60 patients with head and neck cancer required bilateral neck irradiation were planned and treated by simultaneous integrated boost IMRT technique either treated radically or postoperative. Patients undergoing image-guided radiotherapy (IGRT) each with once weekly scheduled cone beam computed tomography (CBCT). The 3D displacements, systematic and random errors were calculated. The appropriate PTV expansion was determined using Van Herk’s formula. Results: Mean 3D displacement was 0.16 cm in the vertical direction, 0.14 cm in the horizontal direction and 0.16 cm in the longitudinal direction. Conclusion: Use of weekly CBCT allows the planning target volume (PTV) expansion to be reduced according to our setup. The appropriate clinical target volume (CTV)-PTV margin for our institute is 0.30 cm, 0.38 cm, and 0.33 cm in the horizontal, vertical, and longitudinal directions, respectively.

Geographical miss of the prostate during image-guided radiotherapy with a 6-mm posterior expansion margin

IntroductionOur department commonly uses a planning target volume (PTV) expansion of 6 mm posterior and 1 cm in all other directions when treating prostate cancer patients with image‐guided radiotherapy (IGRT). This study aimed to test the adequacy of this PTV expansion by assessing geographical miss of the prostate on post‐treatment cone‐beam CT (CBCT) and identify those at risk of geographical miss.MethodsTwenty‐two prostate cancer patients receiving IGRT with implanted fiducial markers underwent daily pre‐treatment orthogonal kV imaging followed by a post‐treatment CBCT for a total of 432 fractions. The prostate was outlined on all CBCTs. For each imaging set, the volume of geographic miss was measured by subtracting the PTV from the planning CT and prostate volume on the post‐treatment CBCT.ResultsThe prostate volume moved outside the PTV by >0.01 cc in 9% of fractions (39/432). This occurred in 13 (59%) of 22 patients. Large prostates >40 cc and >50 cc had significantly more geographical miss events (both P < 0.001). Changes in rectal filling appear to be responsible for prostate motion/deformation in 82% (32/39) of fractions.ConclusionsOur analysis suggests that, despite IGRT, prostate PTV margins are not adequate in some patients, particularly those with large prostates. PTV margins may be reduced in some other patients. Prostate rotation and deformation play an important role in setting margins and may not always be represented accurately by fiducial marker displacements. Individualised and adaptive margins for prostate cancer patients should be a priority for future research.

Development of 3-dimensional transperineal ultrasound for image guided radiation therapy of the prostate: Early evaluations of feasibility and use for inter- and intrafractional prostate localization

PurposeTransperineal ultrasound (TPUS) allows for continuous imaging of the prostate gland, but the accuracy of TPUS has not been rigorously studied. We determined the feasibility of prostate imaging with TPUS and subsequently compared prostate localization with TPUS and computed tomography (CT). Methods and materialsWe completed 2 sequential evaluations of TPUS. The feasibility study included 15 men with localized prostate cancer and tested if TPUS adequately imaged the prostate. Image qualities of the prostate and adjacent normal structures were measured. The subsequent study included 17 men who at the time of initial radiation treatment planning and in 3 subsequent sessions had CT and TPUS imaging performed and compared. ResultsFeasibility of TPUS was confirmed in the first trial. After expected hardware and software modifications were completed, TPUS provided near complete edge definition of the prostate in the final 5 patients in the feasibility trial. The second study allowed for the comparison of 30 image sets. The differences between TPUS and CT in each direction (mean + standard deviation) were found to be 0.06 ± 2.86 mm (anteroposterior), 0.49 ± 3.49 mm (superoinferior), and 0.63 ± 3.27 mm (left-right), with no significant difference between the 2 modalities (all P > .32). The Euclidean distance variance using the 2 techniques was 5.25 ± 1.79 mm, which was significantly different. ConclusionsTPUS provides good imaging of the prostate gland. We noted excellent correlation in gland localization when TPUS is compared with CT scans when comparing routine 3-dimensional positional data. Euclidean distance variation suggests the potential that summation of small errors may in fact lead to significant differences in actual gland positional certainty. The reported difference is within the range of standard planning target volume expansion however requires additional evaluation.

Receiver operating curves and dose-volume analysis of late toxicity with stereotactic body radiation therapy for prostate cancer

PurposeThe purpose of this study was to evaluate a receiver operating characteristic (ROC) curve method to determine dose thresholds with late genitourinary (GU) toxicity after stereotactic body radiation therapy for prostate cancer. Methods and materialsSeventy-eight patients diagnosed with low- to intermediate-risk prostate cancer and treated with stereotactic body radiation therapy alone were reviewed retrospectively. All patients received a total dose of 38 Gy in 4 fractions with a planning target volume expansion of 2 mm. GU toxicity was documented according to the Common Terminology Criteria for Adverse Events, version 4. ROC analysis applied on a logistic regression model was used to determine optimal dosimetric parameters for GU toxicity. ResultsThe median age at treatment was 69 years with a median prostate volume of 46.2 mL. The median prescription isodose line was 67% (interquartile range, 65, 70). The median clinical follow-up was 35.49 months. Late grade 1, 2, and 3 GU toxicity occurred in 21.8%, 19.2%, and 2.6% of cases, respectively. Late grade 2+ GU toxicity was associated with prescription to isodose line (P = .009) and normalized volumes for heterogeneity ≥46 Gy. The ROC method successfully produced thresholds for dose-volume recommendations for both prostate and urethra, including normalized prostate volumes from 46 to 50 Gy, such as volume of target tissue receiving 46% of the prescribed dose (V46) Gy of 36.7% (sensitivity, 71%; specificity, 61%; area under the curve, 0.67) with an associated probability of late GU grade 2+ toxicity of 21%. ConclusionsIntraprostatic heterogeneity should be controlled with potential thresholds at V46 Gy <36.7%, V48 Gy <21%, and V50 Gy <9.5% of the normalized prostate volume to keep late grade 2+ GU toxicity ≤20% with 4-fraction schemes. This may be facilitated with a higher prescription isodose line (>69%).

Inter-Fraction Tumor Volume Response during Lung Stereotactic Body Radiation Therapy Correlated to Patient Variables.

PurposeAnalyze inter-fraction volumetric changes of lung tumors treated with stereotactic body radiation therapy (SBRT) and determine if the volume changes during treatment can be predicted and thus considered in treatment planning.Methods and MaterialsKilo-voltage cone-beam CT (kV-CBCT) images obtained immediately prior to each fraction were used to monitor inter-fraction volumetric changes of 15 consecutive patients (18 lung nodules) treated with lung SBRT at our institution (45–54 Gy in 3–5 fractions) in the year of 2011–2012. Spearman's (ρ) correlation and Spearman's partial correlation analysis was performed with respect to patient/tumor and treatment characteristics. Multiple hypothesis correction was performed using False Discovery Rate (FDR) and q-values were reported.ResultsAll tumors studied experienced volume change during treatment. Tumor increased in volume by an average of 15% and regressed by an average of 11%. The overall volume increase during treatment is contained within the planning target volume (PTV) for all tumors. Larger tumors increased in volume more than smaller tumors during treatment (q = 0.0029). The volume increase on CBCT was correlated to the treatment planning gross target volume (GTV) as well as internal target volumes (ITV) (q = 0.0085 and q = 0.0039 respectively) and could be predicted for tumors with a GTV less than 22 mL. The volume increase was correlated to the integral dose (ID) in the ITV at every fraction (q = 0.0049). The peak inter-fraction volume occurred at an earlier fraction in younger patients (q = 0.0122).ConclusionsWe introduced a new analysis method to follow inter-fraction tumor volume changes and determined that the observed changes during lung SBRT treatment are correlated to the initial tumor volume, integral dose (ID), and patient age. Furthermore, the volume increase during treatment of tumors less than 22mL can be predicted during treatment planning. The volume increase remained significantly less than the overall PTV expansion, and radiation re-planning was therefore not required for the purpose of tumor control. The presence of the studied correlations suggests that the observed volumetric changes may reflect some underlying biologic process rather than random fluctuations.