Planning CT Research Articles

Region-adaptive Deformable Registration of CT/MRI Pelvic Images via Learning-based Image Synthesis.

Registration of pelvic CT and MRI is highly desired as it can facilitate effective fusion of two modalities for prostate cancer radiation therapy, i.e., using CT for dose planning and MRI for accurate organ delineation. However, due to the large inter-modality appearance gaps and the high shape/appearance variations of pelvic organs, the pelvic CT/MRI registration is highly challenging. In this paper, we propose a region-adaptive deformable registration method for multi-modal pelvic image registration. Specifically, to handle the large appearance gaps, we first perform both CT-to-MRI and MRI-to-CT image synthesis by multi-target regression forest (MT-RF). Then, to use the complementary anatomical information in the two modalities for steering the registration, we select key points automatically from both modalities and use them together for guiding correspondence detection in the region-adaptive fashion. That is, we mainly use CT to establish correspondences for bone regions, and use MRI to establish correspondences for soft tissue regions. The number of key points is increased gradually during the registration, to hierarchically guide the symmetric estimation of the deformation fields. Experiments for both intra-subject and inter-subject deformable registration show improved performances compared with state-of-the-art multi-modal registration methods, which demonstrate the potentials of our method to be applied for the routine prostate cancer radiation therapy.

CBCT-guided evolutive library for cervical adaptive IMRT.

In the context of adaptive radiation therapy (ART) for locally advanced cervical carcinoma (LACC), this study proposed an original cone-beam computed tomography (CBCT)-guided "Evolutive library" and evaluated it against four other known radiotherapy (RT) strategies. For 20 patients who underwent intensity-modulated radiation therapy (IMRT) for LACC, three planning CTs [with empty (EB), intermediate (IB), and full (FB) bladder volumes], a CT scan at 20 Gy and bi-weekly CBCTs for 5 weeks were performed. Five RT strategies were simulated for each patient: "Standard RT" was based on one IB planning CT; "internal target volume (ITV)-based RT" was an ITV built from the three planning CTs; "RT with one mid-treatment replanning (MidTtReplan)" corresponded to the standard RT with a replanning at 20 Gy; "Pretreatment library ART" using a planning library based on the three planning CTs; and the "Evolutive library ART", which was the "Pretreatment library ART" strategy enriched by including some CBCT anatomies into the library when the daily clinical target volume (CTV) shape differed from the ones in the library. Two planning target volume (PTV) margins of 7 and 10 mm were evaluated. All the strategies were geometrically compared in terms of the percentage of coverage by the PTV, for the CTV and the organs at risk (OAR) delineated on the CBCT. Inadequate coverage of the CTV and OARs by the PTV was also assessed using deformable image registration. The cumulated dose distributions of each strategy were likewise estimated and compared for one patient. The "Evolutive library ART" strategy involved a number of added CBCTs: 0 for 55%; 1 for 30%; 2 for 5%; and 3 for 10% of patients. Compared with the other four, this strategy provided the highest CTV geometric coverage by the PTV, with a mean (min-max) coverage of 98.5% (96.4-100) for 10 mm margins and 96.2% (93.0-99.7) for 7 mm margins (P < 0.05). Moreover, this strategy significantly decreased the geometric coverage of the bowel. CTV undercoverage by PTV occurred in the anterior and superior uterine regions for all strategies. The dosimetric analysis at 7 mm similarly demonstrated that the "Evolutive library ART" increased the V42.75Gy of the CTV by 27%, 20%, 13%, and 28% compared with "Standard RT", "ITV-based RT", "MidTtReplan", and "Pretreatment library ART", respectively. The dose to the bowel was also decreased by the "Evolutive library ART" compared with that by the other strategies. The "Evolutive library ART" is a personalized ART strategy that comprises a pretreatment planning library of three CT scans, enriched for half of the patients by one to three per-treatment CBCTs. This original strategy increased both the CTV coverage and bowel sparing compared with all the other tested strategies and enables us to consider a PTV margin reduction.

Proton Beam Therapy without Fiducial Markers Using Four-Dimensional CT Planning for Large Hepatocellular Carcinomas.

We evaluated the effectiveness and toxicity of proton beam therapy (PBT) for hepatocellular carcinomas (HCC) >5 cm without fiducial markers using four-dimensional CT (4D-CT) planning. The subjects were 29 patients treated at our hospital between March 2011 and March 2015. The median total dose was 76 Cobalt Gray Equivalents (CGE) in 20 fractions (range; 66–80.5 CGE in 10–32 fractions). Therapy was delivered with end-expiratory phase gating. An internal target volume (ITV) margin was added through the analysis of respiratory movement with 4D-CT. Patient age ranged from 38 to 87 years (median, 71 years). Twenty-four patients were Child–Pugh class A and five patients were class B. Tumor size ranged from 5.0 to 13.9 cm (median, 6.9 cm). The follow-up period ranged from 2 to 72 months (median; 27 months). All patients completed PBT according to the treatment protocol without grade 4 (CTCAE v4.03 (draft v5.0)) or higher adverse effects. The two-year local tumor control (LTC), progression-free survival (PFS), and overall survival (OS) rates were 95%, 22%, and 61%, respectively. The LTC was not inferior to that of previous reports using fiducial markers. Respiratory-gated PBT with 4D-CT planning without fiducial markers is a less invasive and equally effective treatment for large HCCs as PBT with fiducial markers.

CASPIR trial: Using prostatic calculi as an alternative to fiducial markers for IGRT in for localized prostate cancer.

60 Background: Image guided Radiotherapy (IGRT) for prostate cancer (PCA) frequently employs surgically implanted fiducial markers (FMs). However, it is estimated that up to 35% of prostate radiotherapy patients have prostatic calculi (PC) visible on treatment cone beam CTs (CBCT). The purpose of this clinical trial is to directly compare FMs with PCs as an aid to prostate IGRT. Methods: We report data from a single institution prospective clinical trial investigating the feasibility of using prostate calcifications as natural FMs for IGRT. Patients planned for standard prostate radical EBRT +/- brachytherapy were eligible. Prior to CT planning, 3 gold fiducial markers are inserted into the prostate by the trans-perineal route under TRUS guidance. PCs visible within the PTV were contoured. Participants were aligned to FMs for EBRT using daily CBCT image guidance on a Varian TrueBeam linac. Off-line, a single experienced user analyses CBCTs using Image Registration in Eclipse (version 13.6). Random and systematic set-up errors are determined based on FMs, PCs (where present), prostate gland (PG) and bony landmarks (BL) and CTV-PTV margins derived for each data set. Results: 30 participants with PC have been recruited. Data from the first 19 patients (365 fractions), resulted in 2555 individual image registrations (7665 individual data points). The PTV margins required based on each reference structure are summarised in Table 1. The maximum difference between the CTV-PTV(PC) margin and CTV-PTV(FM) margin is 2.2mm in the X or L/R dimension. Margins required for FM, PG and PC in the Y and Z dimensions are comparable, with a maximum difference of 0.5mm between CTV-PTV(PC) and CTV-PTV(PG). Conclusions: Preliminary results from this study demonstrate some evidence to support the use of PCs as an alternative to FMs for prostate IGRT. Future analysis will include location of PC according to the PIRADs schema and patient feedback in relation to FM implantation. Clinical trial information: NA. [Table: see text]

Abstract OT2-03-04: Feasibility of assessing radiation response with MRI/CT directed preoperative accelerated partial breast irradiation in the prone position for hormone responsive early stage breast cancer

Abstract Background: Accelerated partial breast irradiation (APBI) delivers adjuvant radiation (RT) to the 1-2 cm of the breast at highest risk for recurrence surrounding the lumpectomy (L) cavity over 5-8 days and is an alternative to standard whole breast irradiation for hormone sensitive (HS) stage 1 (T1, N0) breast cancer (BC) based on 2 randomized controlled trials. External beam methods for APBI are common but have notable inherent drawbacks that include: inter-fraction inaccuracy due to patient setup based on anatomy, intra fraction error related to patient or respiratory motion, and inaccurate geometric targeting by relying on L cavity position instead of the tumor position. Postoperative RT has other limitations including delivery in the setting of disrupted blood or lymphatic supply that may be suboptimal for radio sensitivity and it eliminates observation of radiation-induced tumor response. MRI is an established tool for measuring BC extent and response from neoadjuvant systemic therapy. It's hypothesized that MRI directed pre-operative APBI using intensity modulated radiotherapy (IMRT) with image guidance (IGRT) will improve RT delivery, and that MRI features can be identified to correlate with pathologic radiation response. Trial Design: There are 2 cohorts to this single arm prospective trial. The first cohort is for establishing and verifying patient flow and image fusion between MRI, CT and RT planning. In the second cohort eligible patients will receive preoperative APBI 38.5 Gy in 10 fractions BID with IMRT, IGRT in the prone position using MRI defined targets fused to CT treatment planning. Eligibility: For cohort 1 it is HS Stage 1 BC that has completed CT in prone position for RT planning. Eligibility for cohort 2 requires: age &amp;gt; 50 yo, clinical stage 1 BC, HS, HER2 negative, intending L, clinically negative axilla verified by ultrasound, able to tolerate the prone position, and MRI with contrast. Specific aims: To determine the reproducibility of MRI directed preoperative APBI based on meeting 3 criteria: ability to define RT targets by MRI, quality of RT plans and completion of treatment (APBI and surgery). Additional aims include assessing toxicity, cosmetic outcome, local regional cancer control and collection of tissue for correlative studies. Statistical methods: The optimal two-stage design by Simon is used. Sample size for cohort 2 is based on the first endpoint. 19 eligible patients will be required in the first stage; if 3 or more treatments are scored unacceptable, then early stopping will be recommended. Otherwise, accrual will continue to a total accrual of 30. If &amp;gt; 4 of 30 treatments are scored unacceptable, the technique will be considered not reproducible, and a Phase II study will not be pursued. Under the null hypothesis of an 80% reproducibility rate, this two-stage design has an expected sample size of 24.4. Patient accrual to cohort 1 has completed the targeted accrual of 3. Patient accrual to Cohort 2 is 5/30. Contact information: Soyhun Mc Elroy (Sohyun.McElroy@osumc.edu) or Julia White (Julia.White@osumc.edu) Funding source: Susan G Komen Breast Cancer Foundation Grant # GRT00035216 Citation Format: White J, McElroy S, Sekhon A, Wei L, Bazan J, Yang X, DiCostanzo D, Kuhn K, Gupta N, Knopp M. Feasibility of assessing radiation response with MRI/CT directed preoperative accelerated partial breast irradiation in the prone position for hormone responsive early stage breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT2-03-04.

Effect of different patient positions on target dose coverage in rectal cancer IMRT

Objective To compare the effect between the supine and prone patient positions upon target dose coverage during intensity-modulated radiotherapy (IMRT) for rectal cancer, aiming to provide clinical reference for the selection of position for rectal cancer patients. Methods Twenty-four patients diagnosed with rectal cancer receiving postoperative adjuvant radiotherapy were selected and divided into the supine (n=12) and prone position groups (n=12). Before and during the IMRT (1-4 weeks), all patients received CT scans, which were defined as: Plan, 1W, 2W, 3W and 4W, respectively. The organs at risk were delineated based on CT scan images. Plan, 1W, 2W, 3W and 4W CT scan images were fused. The CTV and PTV from Plan CT scan were copied to the 1-4W CT scan images, and the therapeutic plans from Plan CT scan were copied as well. The target dose coverage was assessed and the failure rate of target dose coverage was calculated. The couch-position data for each patient during each cycle of IMRT were recorded by using the MOSAIQ network and the overall deviation (S) of couch position was calculated. Results The failure rates of CTV and PTV target dose coverage in the prone position group were higher than those in the supine position group (18.60% VS 0%, 69.76% VS 53.65%). The S value was significantly correlated with the target dose coverage (r=-0.683, P=0.000). The S value in the prone position group was (1.23±0.76) cm, significantly greater than (0.28±0.18) cm in the supine position (P=0.001), and the most significant deviation was noted in the y (head and foot) and z (frontal and dorsal) directions (P=0.003 and 0.003). Compared with the supine group, the V5 and V10 of the small intestine were significantly less (P=0.003 and 0.004) and the chronic toxicity (NTCPC) was considerably reduced (P=0.041) in the prone position group. Conclusions A better target dose coverage can be maintained during IMRT with a supine position during rectal cancer IMRT, whereas the positioning repeatability is worsened with a prone position due to use of the belly board, thereby affecting the target dose coverage. Although the prone position combined with belly board can reduce the tolerated dosage of the small intestine, effective measures should be taken to guarantee the patient positioning repeatability. Key words: Rectal neoplasms/intensity-modulated radiotherapy; Radiotherapy dosage; Belly board

Dosimetric evaluation of magnetic resonance-generated synthetic CT for radiation treatment of rectal cancer.

PurposeThe purpose of this study was to assess the dosimetric equivalence of magnetic resonance (MR)-generated synthetic CT (synCT) and simulation CT for treatment planning in radiotherapy of rectal cancer.MethodsThis study was conducted on eleven patients who underwent whole-body PET/MR and PET/CT examination in a prospective IRB-approved study. For each patient synCT was generated from Dixon MR using a model-based method. Standard treatment planning directives were used to create a four-field box (4F), an oblique four-field (O4F) and a volumetric modulated arc therapy (VMAT) plan on synCT for treatment of rectal cancer. The plans were recalculated on CT with the same monitor units (MUs) as that of synCT. Dose-volume metrics of planning target volume (PTV) and organs at risk (OARs) as well as gamma analysis of dose distributions were evaluated to quantify the difference between synCT and CT plans. All plans were calculated using the analytical anisotropic algorithm (AAA). The VMAT plans on synCT and CT were also calculated using the Acuros XB algorithm for comparison with the AAA calculation.ResultsMedians of absolute differences in PTV metrics between synCT and CT plans were 0.2%, 0.2% and 0.3% for 4F, O4F and VMAT respectively. No significant differences were observed in OAR dose metrics including bladder V40Gy, mean dose in bladder, bowel V45Gy and femoral head V30Gy in any techniques. Gamma analysis with 2%/2mm dose difference/distance to agreement criteria showed median passing rates of 99.8% (range: 98.5 to 100%), 99.9% (97.2 to 100%), and 99.9% (99.4 to 100%) for 4F, O4F and VMAT, respectively. Using Acuros XB dose calculation, 2%/2mm gamma analysis generated a passing rate of 99.2% (97.7 to 99.9%) for VMAT plans.ConclusionSynCT enabled dose calculation equivalent to conventional CT for treatment planning of 3D conformal treatment as well as VMAT of rectal cancer. The dosimetric agreement between synCT and CT calculated doses demonstrated the potential of MR-only treatment planning for rectal cancer using MR generated synCT.

Gender-based differences of abdominal adipose tissue distribution in non-small cell lung cancer patients

Background: Lung cancer is a malignant tumor with high lethality, responsible for about 28% of all cancer deaths. In this study, using a quantitative CT imaging-based approach, we aimed to investigate the differences of abdominal adipose tissue distribution in patients with non-small cell lung cancer (NSCLC) according to gender. Methods: A group of 66 patients with NSCLC at first diagnosis [male: 45, mean age: 67.3 years (range, 51.0–88.0 years); female: 21, mean age: 62.4 years (range, 44.0–84.0 years)] was included. As a control group, 70 patients without history of malignancies who have undergone a chest-abdomen CT for pre-operative cardiovascular surgery planning [male: 42, mean age: 62.7 years (range, 40.0–83.0 years); female: 28, mean age: 66.4 years (range, 39.0–83.0 years)] was included. We calculated total adipose area (TAA), visceral adipose area (VAA) and subcutaneous adipose area (SAA) using OsiriX to analyze cross-sectional CT images. The differences were analyzed using the Student’s t -test (P Results: In the female group, the visceral/subcutaneous (V/S) ratio was higher in the control group than in patients. Conversely, in the male group we found a higher V/S ratio in patients then controls. Considering male and female together, the age parameter showed a significant positive correlation with the amount of visceral (r=0.390; P=0.001) and total (r=0.270; P=0.030) fat in the patients. Dividing the groups between male and female, the age parameter showed a significant positive correlation with the amount of visceral fat in the female patients (r=0.440; P=0.049), visceral fat in the male patients (r=0.320; P=0.030), subcutaneous fat in the female patients (r=0.480; P=0.030) and total fat in the female patients (r=0.490; P=0.020). Conclusions: The results of this study are in line with the concept of differential gender-based relationships among abdominal fat distribution, age and NSCLC.

Independent Monte-Carlo dose calculation for MLC based CyberKnife radiotherapy

This work aims to develop, implement and validate a Monte Carlo (MC)-based independent dose calculation (IDC) framework to perform patient-specific quality assurance (QA) for multi-leaf collimator (MLC)-based CyberKnife® (Accuray Inc., Sunnyvale, CA) treatment plans. The IDC framework uses an XML-format treatment plan as exported from the treatment planning system (TPS) and DICOM format patient CT data, an MC beam model using phase spaces, CyberKnife MLC beam modifier transport using the EGS++ class library, a beam sampling and coordinate transformation engine and dose scoring using DOSXYZnrc.The framework is validated against dose profiles and depth dose curves of single beams with varying field sizes in a water tank in units of cGy/Monitor Unit and against a 2D dose distribution of a full prostate treatment plan measured with Gafchromic EBT3 (Ashland Advanced Materials, Bridgewater, NJ) film in a homogeneous water-equivalent slab phantom. The film measurement is compared to IDC results by gamma analysis using 2% (global)/2 mm criteria. Further, the dose distribution of the clinical treatment plan in the patient CT is compared to TPS calculation by gamma analysis using the same criteria.Dose profiles from IDC calculation in a homogeneous water phantom agree within 2.3% of the global max dose or 1 mm distance to agreement to measurements for all except the smallest field size. Comparing the film measurement to calculated dose, 99.9% of all voxels pass gamma analysis, comparing dose calculated by the IDC framework to TPS calculated dose for the clinical prostate plan shows 99.0% passing rate. IDC calculated dose is found to be up to 5.6% lower than dose calculated by the TPS in this case near metal fiducial markers.An MC-based modular IDC framework was successfully developed, implemented and validated against measurements and is now available to perform patient-specific QA by IDC.

4. Application of a novel retrospective method for liver 4D-MRI

Introduction Liver imaging is challenging due to its constant movement with breathing. In Magnetic Resonance Imaging (MRI), different strategies have been developed for organ movement consideration [1] , [2] , [3] . These methods are limited by the temporal resolution, as well as image quality. A novel retrospective gating method for dynamic 3D MR imaging during free breathing was developed [1] and further improved by Celicanin et al. [4] . This work aims of assessing the method and the reconstruction technique for liver cases. The final clinical application is to improve liver lesion delineation for Stereotactic Body Radiation Therapy (SBRT). Methods The innovative 4D MRI approach has been evaluated for liver motion estimation during entire respiratory cycle on a healthy volunteer. It is based on simultaneous acquisition of 2D images and a navigator set using acceleration CAIPIRINHA technique [4] providing no temporal divergence between them. During the entire acquisition time, the navigator is fixed in the same position, while the image position is changing, in order to cover the entire organ during free breathing [1] . The entire respiratory cycle is acquired, using a modified balanced Steady State Free Precession sequence (bSSFP) and is reconstructed in a retrospective manner ( Fig. 1 ). Images are acquired with a 1.5T MRI (MAGNETOM Aera; Siemens Medical Solutions, Erlangen, Germany), using an 18-channel design body flex coil. The 3.5 mm 2D axial slices are obtained, using the following sequence parameters: TE = 2.27 ms, TR = 591.97 ms, FA = 70 °, FOV = 37 × 37 cm2, matrix = 256 × 246. Total acquisition time is 33.175 s (0.83 s per slice). Results The preliminary results obtained on a healthy volunteer are shown in Fig. 1 . Images are characterized by high resolution and great contrast, making this method promising for liver lesion examination. The reconstruction of 4D MRI and the sequence optimization to cover the entire respiration cycle with the appropriate time sampling is ongoing work. Conclusions The benefit of MRI acquisition in treatment position to improve lesion contouring for liver SBRT has already been demonstrated [5] . The presented 4D MRI method represents a highly time efficient technique for the free breathing liver motion registration, giving the possibility to sort and reconstruct the images according to the respiratory phases. It will allow registration with 4D CT planning, likely to improve delineation accuracy. The same approach can be applied to study moving organs others than liver.

Abdominal imaging dose in radiology and radiotherapy – Phantom point dose measurements, effective dose and secondary cancer risk

PurposeTo compare abdominal imaging dose from 3D imaging in radiology (standard/low-dose/dual-energy CT) and radiotherapy (planning CT, kV cone-beam CT (CBCT)). MethodsDose was measured by thermoluminescent dosimeters (TLD’s) placed at 86 positions in an anthropomorphic phantom. Point, organ and effective dose were assessed, and secondary cancer risk from imaging was estimated. ResultsOverall dose and mean organ dose comparisons yield significantly lower dose for the optimized radiology protocols (dual-source and care kV), with an average dose of 0.34±0.01 mGy and 0.54±0.01 mGy (average ± standard deviation), respectively. Standard abdominal CT and planning CT involve considerably higher dose (13.58 ± 0.18 mGy and 18.78±0.27 mGy, respectively). The CBCT dose show a dose fall-off near the field edges. On average, dose is reduced as compared with the planning or standard CT (3.79 ± 0.21 mGy for 220° rotation and 7.76 ± 0.37 mGy for 360°), unless the high-quality setting is chosen (20.30 ± 0.96 mGy). The mean organ doses show a similar behavior, which translates to the estimated secondary cancer risk. The modelled risk is in the range between 0.4 cases per million patient years (PY) for the radiological scans dual-energy and care kV, and 300 cases per million PY for the high-quality CBCT setting. ConclusionsModern radiotherapy imaging techniques (while much lower in dose than radiotherapy), involve considerably more dose to the patient than modern radiology techniques. Given the frequency of radiotherapy imaging, a further reduction in radiotherapy imaging dose appears to be both desirable and technically feasible.

Regression and statistical shape model based substitute CT generation for MRI alone external beam radiation therapy from standard clinical MRI sequences

In MR only radiation therapy planning, generation of the tissue specific HU map directly from the MRI would eliminate the need of CT image acquisition and may improve radiation therapy planning. The aim of this work is to generate and validate substitute CT (sCT) scans generated from standard T2 weighted MR pelvic scans in prostate radiation therapy dose planning. A Siemens Skyra 3T MRI scanner with laser bridge, flat couch and pelvic coil mounts was used to scan 39 patients scheduled for external beam radiation therapy for localized prostate cancer. For sCT generation a whole pelvis MRI (1.6 mm 3D isotropic T2w SPACE sequence) was acquired. Patients received a routine planning CT scan. Co-registered whole pelvis CT and T2w MRI pairs were used as training images. Advanced tissue specific non-linear regression models to predict HU for the fat, muscle, bladder and air were created from co-registered CT-MRI image pairs. On a test case T2w MRI, the bones and bladder were automatically segmented using a novel statistical shape and appearance model, while other soft tissues were separated using an Expectation-Maximization based clustering model. The CT bone in the training database that was most ‘similar’ to the segmented bone was then transformed with deformable registration to create the sCT component of the test case T2w MRI bone tissue. Predictions for the bone, air and soft tissue from the separate regression models were successively combined to generate a whole pelvis sCT. The change in monitor units between the sCT-based plans relative to the gold standard CT plan for the same IMRT dose plan was found to be (mean ± standard deviation) for 39 patients. The 3D Gamma pass rate was (2 mm/2%). The novel hybrid model is computationally efficient, generating an sCT in 20 min from standard T2w images for prostate cancer radiation therapy dose planning and DRR generation.

Multiple-CT optimization of intensity-modulated proton therapy – Is it possible to eliminate adaptive planning?

Background and purposeWe hypothesized that a plan’s robustness to anatomical changes can be improved by optimizing with multiple CT scans of a patient. The purpose of this study was to determine whether an intensity modulated proton therapy (IMPT) plan could be developed to meet dose criteria on both planning and adaptive CT plans. Material and methodsEight lung cancer patients who underwent adaptive IMPT were retrospectively selected. Each patient had two CTs: a primary planning CT (PCT) and an adaptive planning CT (ACT), and IMPT plans associated with the scans. PCT and ACT were then used in combination to optimize one plan (MCT plan). The doses to the target and organs at risk from the PCT plan, ACT plan, P-ACT plan (PCT plan calculated on ACT data), and MCT plans calculated on both CTs were compared. ResultsThe MCT plan maintained the D95% on both CTs (mean, 65.99 Gy on PCT and 66.02 Gy on ACT). Target dose coverage on ACT was significantly better with the MCT plan than with the P-ACT plan (p = 0.01). MCT plans had slightly higher lung V20 (0.6%, p = 0.02) than did PCT plans. The various plans showed no statistically significant difference in heart and spinal cord dose. ConclusionsThe results of this study indicate that an IMPT plan can meet the dose criteria on both PCT and ACT, and that MCT optimization can improve the plan’s robustness to anatomical change.

Abstract ID: 139 Monte Carlo simulations for imaging in proton therapy

Proton therapy is rapidly gaining importance in the field of radiotherapy, because of its potential to deliver the planned dose over a small depth range and sparing dose to healthy tissue, when compared to conventional radiotherapy. Proton therapy, however, makes the need of new imaging modalities for treatment planning, based on direct measurements of tissue stopping power and eliminating the need to convert tissue density – as measured in conventional X-ray Computed Tomography) – to stopping power, upon which treatment planning is based [1] . The expected benefits of proton CT (pCT) for treatment planning in Proton Radiotherapy are producing great interest worldwide to develop instruments for clinical-quality pCT. The PRaVDA (Proton Radiotherapy Verifications and Dosimetry Applications) consortium has developed a novel purely solid state system and associated image reconstruction for pCT [2] , [3] . Custom detectors for the PRaVDA instrument include Silicon Strip Detectors (SSD) and Monolithic Active Pixel Sensors (MAPS). To assist design decisions, detector development and development of image reconstruction algorithms, comprehensive Geant4-based Monte Carlo simulations were developed, comprising realistic beam-line sources for two proton sources where the PRaVDA instrument has been tested (MC40 cyclotron at the University of Birmingham and iThemba LABS cyclotron), full device geometry and realistic readout for both SSDs and MAPSs. The full paper will focus on simulations of MAPS for imaging in proton therapy. The full read-out chains of a MAPS – including charge diffusion, collection, sharing and digitalization, has been simulated through the development of ad hoc classes integrated in the standard Geant4 toolkit. An experimental validation of the model (at two different proton sources) will be provided and the contribution of these simulations to assess imaging capabilities of MAPS, in the context of proton therapy, will be highlighted.

Superiority of CT Myelography over MRI in Delineating the Spinal Cord during Spine Stereotactic Radiosurgery

Spine stereotactic radiosurgery (sSRS) has an important role in the management of primary and metastatic spine tumors. A critical component of sSRS is the accurate delineation of the spinal cord to prevent severe and potentially irreversible myelopathy. CT myelography (myelo) and magnetic resonance imaging (MRI) registration are commonly used during sSRS planning to delineate the spinal cord. The aim of this study was to rigorously compare these two modalities and the potential impact they have on planning outcomes. Between 3/2016 and 10/2016, 24 cases of sSRS were simulated using CT myelo with a companion diagnostic MRI. Two independent and blinded physicians contoured the MRI and myelo cords. Registration was then performed to the vertebral column and spinal canal. Ninety-six treatment plans were generated to deliver either 16 Gy or 18 Gy in a single fraction to the tumor planning target volume (PTV), using either MRI or CT myelo defined cords as an avoidance structure. CT myelo cord D.01cc, cord D10%, and PTV D99% were then calculated. MRI and CT myelo spinal cord volumes were compared using two-tailed paired t-test, and Dice similarity coefficients were calculated to assess their spatial overlap (where 0 equals no overlap and 1 equals perfect overlap). Thirteen (54%) cases were post-op and 11 (46%) cases were non-operated. The mean Dice similarity coefficient was 0.68 +/- 0.11. There were no significant differences in cord volumes (mean 4.7 +/- 2.5 cc for MRI vs. 4.5 +/- 2.4 cc for CT myelo, p=0.25), suggesting that the majority of discordance was spatial rather than volumetric. For post-op cases, there was a trend towards greater cord volume on MRI compared to CT myelo (5.1 +/- 1.5 cc vs. 4.7 +/- 1.1 cc, respectively, p = 0.088). When the MRI defined cords were used for treatment planning, PTV coverage (PTV D99%) was significantly less than with myelo-based treatment planning (for 16 Gy sSRS, 13.5 vs. 14.1 cc, p = 0.008; for 18 Gy sSRS, 14.6 vs. 15.2 cc, p = 0.012). Cord doses were significantly greater with MRI planning as well. D0.1 cc for 16 Gy plans for MRI vs. CT myelo was 12.6 +/- 1.9 Gy vs. 10.4 +/- 1.5 Gy (p<0.001), and for 18 Gy plans was 13.4 +/- 2.3 Gy vs. 11.0 +/- 1.5 Gy (p<0.001). 26 of the 48 MRI plans (54%) exceeded cord dose constraints, with one patient having a D0.1 cc of 18.2 Gy (EQD2 of ∼90 Gy). There are significant spatial differences in MRI and CT myelo defined spinal cords. MRI-based planning consistently resulted in worse PTV coverage and higher doses to the spinal cord. Spinal cord doses were unacceptably high in > 50% of MRI planned sSRS cases. Our data supports spinal CT myelography as the gold-standard for spinal cord delineation, and caution should be used when relying on MRI registration to define the cord for single fraction sSRS.

Evaluation of Differences Between Estimated Delivered Dose and Planned Dose in Nasopharynx Patients Using Deformable Image Registration and Dose Accumulation

To investigate differences in planned dose and estimated delivered dose using deformable image registration (DIR) and dose accumulation for clinical target volumes (CTV) and organs at risk (OAR). Fifty-two nasopharynx patients treated with chemoradiotherapy [70 Gy (high-dose) and 56Gy (low-dose) in 35 fractions] from 2013 and 2015 were included. All clinical plans used 6 MV intensity modulated radiation therapy (IMRT) and daily 3D kV cone beam CT (CBCT) image guidance. Retrospective dose accumulation was performed in RayStation v4.5.2 as follows: DICOM RT data (CT image, plan, dose, and contours) were imported from the clinical planning system. Daily CBCTs were also imported and deformably registered to the planning CT. Daily delivered dose was calculated on the CBCTs and deformed back to and accumulated onto the planning CT to estimate the delivered dose. The planned and delivered doses were compared using representative dose metrics for primary CTVs and OARs including brainstem, mandible, spinal cord, and right and left parotid glands. The impact of daily set-up variation and anatomical changes on target coverage and OAR doses was evaluated by comparing planned dose vs. delivered dose. Relative differences in CTV D98 calculated as percentage of planned dose was used to assess target coverage. The mean relative difference in D98 for 70 Gy CTVs was 0.8% (median 1.1%, range -1.8 to2.6%). The mean relative difference in D98 for 56 Gy CTVs was negligible (median 0.1%, range -2.8 to2.2%). The median (range) maximum dose to 0.1 cc of the brainstem was similar between planned and delivered: 53.0 Gy (40.7-61.5 Gy) and 52.2 Gy (40.0-61.7 Gy). Although some cases exceeded the nominal tolerance dose of 54 Gy in the plan, other cases planned under this tolerance did not exceed 54 Gy in estimated delivered dose. The median maximum dose to 0.1cc of the spinal cord and mandible was 37.8 Gy and 72.0 Gy and delivered dose (range) was 38.8 Gy (30.4-45.8 Gy) and 72.2 Gy (62.9-75.4 Gy), respectively. The D50 planned median dose, delivered median dose (range) for the right and left parotid was 34.4 Gy, 39.3 Gy (23.5-72.3 Gy), and 37.3 Gy, 40.6 Gy (18.6-68.1 Gy). The median planned, delivered dose (range) for the right and left parotid mean dose was 38.4 Gy, 40.3 Gy (30.1-69.8 Gy) and 40.5 Gy, 41.7 Gy (25.3-61.9 Gy). No large differences were seen between planned and delivered OAR doses for the evaluated metrics. Outliers were identified (±2 SD from the average) for the parotids, indicating that variation can be expected for this OAR and warrants further investigation. There was minimal dosimetric change on the serial OARs; the right and left parotids received greater dose than planned. Further studies are required to investigate the impact of this dosimetric change and to identify patients who can benefit from adaptive radiotherapy.

A Radiomic Prognostic Index Refines Risk Models for Distant Metastasis in HPV-Related Oropharyngeal Cancer

Distant metastasis (DM) is the main cause of treatment failure in human papillomavirus (HPV)-related oropharyngeal cancers (OPC). However, predicting DM remains challenging. We hypothesize that quantitative imaging (i.e. radiomic) features may help identify primary tumor features associated with higher risk of DM. We retrieved radiotherapy planning CT scans for 280 UICC/AJCC 8th ed. stage I-III p16-positive OPC patients treated with definitive radiotherapy or chemoradiotherapy at a single institution between 2005 and 2010. Gross tumor volumes (GTVs) were previously contoured by each treating radiation oncologist. A radiomic prognostic index (RPI) was derived based on four validated prognostic radiomic features from tumor intensity, shape, texture, and wavelet feature groups. RPIs were extracted from each GTV based on published algorithms. We used univariate and multivariate analysis with Cox proportional hazards models to identify predictors of DM. Feature selection for multivariate models was performed using recursive partitioning analysis (RPA) and validated. Receiver-operating characteristic (ROC) curves were used to compare models. Median follow-up was five years. There were a total of 34 DM events. Factors associated with increased risk of DM included UICC/AJCC 8th ed. stage III (T4 or N3) (73/280; p<0.001), large GTV (140/280; p=0.048), and high risk RPI (25/280; p<0.001). High risk RPI remained significant (p<0.001) on multivariate analysis. RPA confirmed RPI as a key predictor segregating p16-positive OPCs into low (n=255) and high (n=25) risks of DM with 3-year distant control rates of 91% (0.88-0.95) and 50% (0.32-0.78) respectively. Area under the ROC curve for the RPI-based DM model was 0.72 (0.62-0.82) compared with 0.65 (0.56-0.74) for the conventional stage-based DM model. In subgroup analyses, the RPI consistently stratified patients for DM risk, particularly for those cohorts with greater risk, such as UICC/AJCC 8th ed. stage III cancers. The four-feature RPI can be used alone or in conjunction with other clinical or treatment characteristics to classify HPV-related OPC patients by DM risk. The RPI may therefore allow for greater precision in selection of patients for systemic therapies for HPV-related OPC.

Treatment Outcomes of Chemoradiation in Anaplastic Gliomas

Gliomas account for 80% of primary malignant brain tumors. Standard treatment for grade III gliomas is surgical resection followed by radiotherapy (RT). Evidence for concurrent and adjuvant chemotherapy is not as robust as for Glioblastoma. The aim of the study was to analyze the clinical profile and survival of patients with anaplastic gliomas treated at our institute. A retrospective analysis of patients with histopathological diagnosis of anaplastic gliomas from January 2010 to December 2015 was done from the treatment and follow up records. Patients had undergone maximal safe resection and had received postoperative radiotherapy (60 Gy) with or without concurrent and adjuvant temozolomide. Sub ventricular zone (SVZ) was also contoured along as 5 mm expansion along the lateral margin of the lateral ventricles on axial planning CT fused with MRI. Dosimetric data was collected from the treatment planning system. Statistical analysis was done using SPSS 20 software. A total of 88 patients were included in the study. The median age was 35 years (range 6-68 yrs). 63% were males and 37% females with male: female ratio of 1.75:1. Most common presentation was with headache (61%), seizures (43%), vomiting (18%) or hemiparesis (18%). Out of 88 patients 72 patients received concurrent/adjuvant chemotherapy with temozolomide. Follow up records was available for 75 patients The 6 yr overall survival (OS) was 60%. Patients less than or equal to 35 years had OS of 71 months compared to 65 months for patients above 35 years. (Log rank p= 0.8). Patients having focal neurological deficit at presentation had OS of 65 months compared to 71 months in patients without focal neurological deficit. (Log rank p= 0.6). Surgical extent defined by operating surgeon did not correlate with survival. Patients with anaplastic oligodendroglioma histology had OS of 71 months compared to 53 months for anaplastic astrocytoma (log rank p= 0.5). Based on KPS scores pre radiotherapy, KPS <70 had a median OS of 16 months and KPS > 70 had an OS of 65 months. (Log rank p= 0.001) The mean and median dose of ipsilateral SVZ was 51 and 57.7 Gy respectively. Median survival had not yet reached in the subgroup of Gross total resection (GTR) patients who received an ipsilateral SVZ dose of 57 Gy or greater, compared to 30 months for patients receiving < 57 Gy (log rank p= 0.008). 21 patients had documented recurrence with average time to recurrence being 45 months. 14 patients had salvage surgery and two patients underwent only reirradiation. The average survival after recurrence was 12 months. The 6 year overall survival was 60%. Age >35 years, no neurological deficit at presentation, oligodendroglioma histology, KPS ≥ 70 and no recurrence had better overall survival. In a subset of population with gross total resection, SVZ dose of >57 Gy showed improvement in survival.

Long-Term Outcomes for Validation of Cardiac-Sparing Breast Cancer Treatment Techniques

The association between radiation therapy (RT) and ischemic vascular disease (IVD) has been known for many decades. The publication in 2013 of a retrospective study linking RT for left breast cancer to IVD has inspired numerous dosimetric studies aimed at reducing cardiac doses. The cardiac risk has been attributed to attempts to treat internal mammary lymph nodes (IMLN), most commonly using an anterior beam that delivered high doses to the origins of major vessels and much of the myocardium. If a treatment technique is producing clinically significant IVD we should see a detrimental effect on survival for patients with left breast cancers compared to those with right breast cancers. In 1983 our facility began using CT images to guide treatment planning. Initially, conformal molded blocks shaped tangent fields to protect the cardiac profile as much as possible. Anterior or oblique internal mammary fields became very rare. Since 2001 we have used 3D conformal CT planning and multi-leaf collimators to the same purpose. Deep inspiration breath hold is used when indicated. Between 1983 and 2011 a total of 3474 patients (1735 R, 1739 L) with first primary pathologic stages 0-III breast cancers were treated with this philosophy. Treatment generally covered the whole breast with standard doses (typically 45 – 50 Gy) and a boost. Since 1982 patient data has been abstracted by certified cancer registrars from general medical records and RT summary letters, and maintained on an in-house registry system. The registry has current follow-up on 95.6% of all cases in this group and was the source of data for this study. The two groups proved to be very closely matched in patient and tumor characteristics. Survival estimates were calculated for 30 years following diagnosis using the Kaplan-Meier method on 1 day intervals (table). These were compared using the log-rank test. Throughout the 30-year period of analysis the P-value was never smaller than 0.23 (briefly, at 7 years). Clinically significant IMLN recurrence has been very rare. Cause-specific mortality declined substantially after about 15 years but all-cause mortality remained elevated. For any RT technique, the average heart dose is substantially smaller for right breast cancers than it would be for left breast cancers. The equivalent survival seen with these two groups suggests that relatively simple alterations to treatment plans can virtually eliminate excess cardiac mortality from left breast irradiation without adverse consequences.Tabled 1Abstract 2130; Table 1LateralityTime from Dx (Yrs)051015202530RightAt Risk173514988944691935811Survival100.00%87.35%73.30%59.03%46.65%35.84%22.15%Std Err of Survival0.00%0.81%1.28%1.79%2.52%3.80%6.18%LeftAt Risk173914929124691816614Survival100.00%87.29%71.97%59.14%45.73%34.19%28.80%Std Err of Survival0.00%0.81%1.28%1.77%2.58%3.52%6.49% Open table in a new tab

Management of Glenoid Bone Loss in Reverse Shoulder Arthroplasty

Clinical Results and Treatment algorithm for management of severe glenoid bone loss with reverse shoulder arthroplasty with a min 2.4 year followup. Management of significant glenoid bone loss in patients undergoing a Reverse Shoulder Arthroplasty (RSA) poses a significant treatment challenge. The long-term outcome of single stage RSA with glenoid bone grafting is unknown. This study assesses the indications, technique and outcome of RSA with glenoid bone grafting. Between 2001 and 2010, 1074 RSA were performed at our institution. Out of this cohort 94 patients had significant glenoid bone loss. These patients underwent a single or two-stage RSA with glenoid bone grafting. Intra operatively each patient was subcategorized on the basis of the size of the glenoid defect and managed in accordance with a standardized treatment protocol. The defects were sub classified as centric or eccentric and graded from 1-4 based upon their size. A retrospective analysis of the pre and post-operative clinical and radiological outcome was carried out. The mean follow up was 2.4 years, (0.52 years – 10.7 years). Indication for RSA were as follows: 1) 29.3% Cuff tear arthropathy, 2) 27.2% failed prior arthroplasty, 3) 21% chronic dislocation, 4) 17.4% post traumatic cases. During the operation 17 % had a centric defect and 83 % of patients had an eccentric glenoid defect; the bone loss being anterior in the majority (51.1%). Composite glenoid grafts were required in 10 patients and 9 patients required a revision specific glenoid base plate. 92.5% (87/94) of the patients could be managed as a single stage procedure. There was a significant improvement in the Constant score (p value <0.01) and the subjective shoulder test score (SST) (p value <0.05) in all the patients. No correlation was found between the clinical outcome and indication for surgery, age, location of defect and size of defect. 7 patients had complications. There was 1 case of early implant failure (graft & glenoid component), Complex glenoid defects are encountered in less than 10 % of all cases undergoing a RSA (94/ 1074) and the requirement of complex grafts and revision specific base plates is even rarer (0.8% in our cohort). There by the surgeon must possess an easy intraoperative decision making tool to guide them in an often complex surgical procedure. Pre operative assessment of extent and amount of bone defect with 3D-CT-reconstruction is critical for successful operative technique. However in a revision setting often the bone loss exceeds the surgeons expectations. To combat this problem we have classified glenoid defects based upon the intraoperative finding. A treatment protocol is than followed based upon the size and location of each defect. Sufficient primary fixation of the glenoid base plate is a prerequisite for a single stage procedure and is attainable in 92.3% of patients as per our study. The goal of restoration of the glenoid joint line in a coronal plane is imperative to attain a stable prosthesis with impingement free arc of motion. The vast majority of patients could be managed by autografts however in 9.5% (9/94) of patients revision specific glenoid base plate with a longer peg was required. Improved preoperative planning and better prosthesis subtraction CT algorithms will enable an early identification of this patient cohort and avoid intraoperative surprises.