Planning Organ At Risk Volume Research Articles

Prospective Dosimetric Comparison Study Between Volumetric Modulated Arc Therapy and Intracavitary Brachytherapy for Cervical Cancer

Although volumetric modulated arc therapy (VMAT) boost can achieve highly conformal dose distributions for cervical cancer, VMAT has the disadvantage of requiring set-up and organ motion margins. This study prospectively recruited patients with the cervical cancer and compared VMAT plan with intracavitary brachytherapy (ICBT) plan. All patients treated with ICBT for locally advanced cervical cancer between April 2020 and September 2022 were enrolled. Patients had whole-pelvis radiotherapy, followed by CT scans with and without the tandem and ovoid in the same session (for the planning of ICBT and VMAT, respectively). ICBT planning characterizes the high-risk clinical target volume (HR-CTV) as the target volume and the bladder, rectum, sigmoid colon and small bowel loop as the organ at risk (OAR). VMAT planning defines the HR-CTV + 3 mm as the target volume and bladder, rectum + 3 mm (planning organ at risk volume (PRV) rectum), sigmoid colon + 3 mm (PRV sigmoid) and bowel bag as the OAR to account for set-up and organ motion. ICBT and VMAT plans were optimized for maximal dose received by at least 90% (D90%) of the target volume without impairing the dose constraints for the OARs. The prescribed dose (PD) was 26 Gy in 4 fractions. The dose constraints were determined as 25.2 Gy for D2 ml in the bladder and 20 Gy for D2 ml in the other OARs. The D90% and D100% of the target volume and D2 ml of OARs were compared between 2 plans using paired two-tailed Student's t test. Seventeen patients were enrolled. Dose and volume parameters for the 2 plans are shown in Table 1. Of the 17 patients, D90% of the target volume received 100% PD in 4 cases with ICBT plans, in 6 cases for VMAT plans, and in 2 cases with both methods. For D90% of the target volume, ICBT plans were greater than VMAT plans in 4 cases, with a maximum difference of 5.6 Gy (ICBT: 26.0 Gy, SBRT: 20.4 Gy). VMAT plans were higher than ICBT plans in 11 cases, with a maximum difference of 10.3 Gy (ICBT: 14.5 Gy, SBRT: 24.8 Gy). The dose-limiting OARs to attain D90% of target volume were bladder in 12 cases and small bowel loop in 1 case for ICBT plans, while PRV rectum in 11 cases, PRV sigmoid in 4 cases and bowel bag in 1 case for VMAT plans. This prospective study with 17 ICBT-eligible patients revealed D90% of the target volume demonstrated no substantial difference between VMAT and ICBT plans, while D100% showed a significant increase in VMAT plan compared to ICBT plan. Even with a set-up and organ motion margins on the HR-CTV and OARs, VMAT may have a dosimetric advantage over ICBT if the target geometry is complicated and close to the OARs.

Novel simulation for dosimetry impact of diaphragm respiratory motion in four-dimensional volumetric modulated arc therapy for esophageal cancer

Background and purposeThe diaphragm respiratory motion (RM) could impact the target dose robustness in the lower esophageal cancer (EC). We aimed to develop a framework evaluating the impact of different RM patterns quantitatively in one patient, by creating virtual four-dimensional computed-tomography (v4DCT) images, which could lead to tailored treatment for the breathing pattern. We validated virtual 4D radiotherapy (v4DRT) along with exploring the acceptability of free-breathing volumetric modulated arc therapy (FB-VMAT). Methods and MaterialsWe assessed 10 patients with superficial EC through their real 4DCT (r4DCT) scans. v4DCT images were derived from the end-inhalation computed tomography (CT) image (reference CT) and the v4DRT dose was accumulated dose over all phases. r4DRT diaphragm shifts were applied with magnitudes derived from r4DCT scans; clinical target volume (CTV) dose of v4DRT was compared with that of r4DRT to validate v4DRT. CTV dosage modifications and planning organ at risk volume (PRV) margins of the spinal cord were examined with the diaphragm movement. The percentage dose differences (ΔDx) were determined between the v4DRT and the dose calculated on the reference CT image. ResultsThe CTV ΔDx between the r4DRT and v4DRT were within 1% in cases with RM ≦ 15 mm. The average ΔD100% and ΔDmean of the CTV ranging from 5 to 15 mm of diaphragm motion was 0.3% to 1.7% and 0.1% to 0.4%, respectively. All CTV index changes were within 3% and ΔD1cc and ΔD2cc of Cord PRV were within 1%. ConclusionWe postulate a novel method for evaluating the CTV robustness, comparable to the conventional r4DCT method under the diaphragm RM ≦ 15 mm permitting an impact of within 3% in FB-VMAT for EC on the CTV dose distribution.

Account for the Full Extent of Esophagus Motion in Radiation Therapy Planning: A Preliminary Study of the IRV of the Esophagus.

ObjectiveAccounting for esophagus motion in radiotherapy planning is an important basis for accurate assessment of toxicity. In this study, we calculated how much the delineations of the esophagus should be expanded based on three-dimensional (3D) computed tomography (CT), four-dimensional (4D) average projection (AVG), and maximum intensity projection (MIP) scans to account for the full extent of esophagus motion during 4D imaging acquisition.Methods and MaterialsThe 3D and 4D CT scans of 20 lung cancer patients treated with conventional radiotherapy and 20 patients treated with stereotactic ablative radiation therapy (SBRT) were used. Radiation oncologists contoured the esophagus on the 3DCT, AVG, MIP and 25% exhale scans, and the combination of the esophagus in every phase of 4DCT. The union of all 4D phase delineations (U4D) represented the full extent of esophagus motion during imaging acquisition. Surface distances from U4D to 3D, AVG, and MIP volumes were calculated. Distances in the most extreme surface points (1.5 cm most superoinferior, 10% most right/left/anteroposterior) were used to derive margins accounting only for systematic (delineation) errors.ResultsEsophagus delineations on the MIP were the closest to the full extent of motion, requiring only 6.9 mm margins. Delineations on the AVG and 3D scans required margins up to 7.97 and 7.90 mm, respectively. The largest margins were for the inferior, right, and anterior aspects for the delineations on the 3D, AVG, and MIP scans, respectively.ConclusionDelineations on 3D, AVG, or MIP scans required extensions for representing the esophagus’s full extent of motion, with the MIP requiring the smallest margins. Research including daily imaging to determine the random components for the margins and dosimetric measurements to determine the relevance of creating a planning organ at risk volume (PRV) of the esophagus is required.

Deriving optimal planning organ at risk volume margins in prostate external beam radiotherapy.

Planning organ-at-risk volume (PRV) margins can be applied to the bladder and rectum in prostate external beam radiation therapy (EBRT), in order to incorporate the uncertainties resulting from their inter-fraction motion. For each of a total of 16 patients, the bladder and rectum were delineated on CBCT images for five treatment fractions in addition to the planning CT image set. The bladder and rectum boundary displacements across the images were measured and the frequency and size of organ boundary displacements were evaluated. Subsequently, PRV margins were created to cover a specific percentage of organ boundary motion for a specified percentage of the population. In this investigation, two bladder PRV margins were generated to deal with two bladder conditions of low and high-volume variation among fractions. A combined PRV margin was also generated for the rectum by separating the rectum into three parts and deriving independent PRV margins for each segment. Outward coverage and effectiveness metrics allowed evaluation of the margins.

Abstract PS15-16: Evaluation of workflow box mirada software for automatic delineation of left anterior descending coronary artery (LADCA) in order reduce cardiac toxicity for radiotherapy breast cancer treatments

Abstract Purpose/Objective: In order to preserve the patient's cardiac integrity, a good practice that would be simple and quick to implement would be to optimize dose on the left anterior descending coronary artery (LADCA) during dosimetric planning treatment. However, manual delineation of LADCA remains complicated to perform in clinical routine on non-injected CT-scans. To conclude on the feasibility of such a practice, we investigated the automatic delineation robustness of the Mirada software (Mirada Medical, UK) to generate these volumes. Materials/methods: Forty randomly selected CT-scans of breast cancer patients were used. All were delineated by a radiation therapist following international recommendations (Duane et al., 2017). A planning organ at risk volume (PRV) with a 10 mm margin centered on the LADCA was also performed. Among the forty CT-scans, twenty were used to develop the automatic segmentation atlas using “Workflow Box” auto-segmentation algorithm. The remaining twenty other CT-scans were compiled on the software in order to obtain auto-segmented structures. The relevance of the contours was carried out with the Artiview software (Aquilab, Loos-lès-Lille, France) in order to determine both Dice-similarity coefficients (DSC) and Jaccard indexes. Finally, dosimetric planning treatment in volumetric modulated arc therapy conditions was performed using Eclipse treatment planning system (Varian). Results: Because of variability, both in terms of shape and spatial localization, the atlas-based auto-segmentation software did not succeed in LADCA delineation. Then, LADCA contours were not available for DSC and Jaccard indexes assessment. On the other hand, the use of margins on the LADCA made it possible to create such an Atlas. The average DSC is 0.36 ± 0.15 and the Jaccard index reaches 0.23 ± 0.11. The results associated with dosimetry planning treatment are presented in Table 1. The use of a PRV instead of the LADCA contour tends to overestimate the maximum doses by around 30%. However, the mean and median doses are of the same order of magnitude. Conclusion: Small volume structures do not allow the creation of a robust contouring atlas. However, to overcome this limitation, the use of margins to define a PRV has been quite effective. However, it overestimates the maximum doses by about 30%, so the constraints used to limit doses to the coronary arteries during treatment planning will have to be adjusted in this way. Table 1 Dosimetric results from VMAT optimization for breast radiotherapy treatments.Left breastRight breastPRVLADCAPRVLADCAAverage dose (Gy)12.71 ± 6.5413.24 ± 7.485.86 ± 1.345.61 ± 1.39Median Dose (Gy)11.75 ± 6.5713.32 ± 8.335.75 ± 1.325.59 ± 1.27Maximum dose (Gy)33.29 ± 12.8525.28 ± 11.1810.25 ± 1.967.99 ± 2.09 Citation Format: Nicolas Tkatchenko, Pierre Loap, Eliot Nicolas, Youlia Kirova. Evaluation of workflow box mirada software for automatic delineation of left anterior descending coronary artery (LADCA) in order reduce cardiac toxicity for radiotherapy breast cancer treatments [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS15-16.

In Silico Single-Fraction Stereotactic Ablative Radiation Therapy for the Treatment of Thoracic and Abdominal Oligometastatic Disease With Online Adaptive Magnetic Resonance Guidance

PurposeAlthough SABR can improve oncologic outcomes for patients with oligometastatic disease, treatment of metastases near critical organs remains challenging. The purpose of this study is to determine the dosimetric feasibility of delivering magnetic resonance imaging (MRI)-guided adaptive SABR in a single fraction for abdominal and thoracic metastases. Methods and MaterialsPreviously delivered MRI-guided radiation therapy plans for 20 patients with oligometastatic disease in the thorax or abdomen, with 70% (14/20) of the lesions within 8 mm from dose-limiting organs at risk (OARs), were used to simulate the delivery of 24 Gy in a single fraction. Planning objectives included planning target volume (PTV) V95% >90%, optimized PTV (PTVopt) V95% >90%, and PTVopt D99% >20 Gy with no OAR dose violations, where PTVopt removed overlap with nearby planning organ at risk volume (PRV). Single-fraction plans were simulated on the first 5 daily setup breath-hold MRI scans, and the plans were reoptimized to consider variations in setup position and anatomy. ResultsThe mean PTV V95% for single-fraction SABR plans was lower compared with multifraction plans (mean 85.4% vs 92.6%, P = .02), but mean PTVopt V95% was not different (95.3% vs 98.2%, P = .62). After reoptimization of the single-fraction plan to the treatment day MRI, there was an increase in mean PTV V95% (85.0% vs 88.1%, P = .05), increase in mean PTVopt V95% (92.7% vs 96.3%, P = .02), increase in mean PTVopt D99% (19.7 Gy vs 23.8 Gy, P < .01), increase in mean frequency of meeting PTV D99% >20 Gy (52% vs 87%, P < .01), and increase in mean gross tumor volume minimum dose (17.5 Gy vs 19.3 Gy, P < .01). Reoptimization decreased mean frequency of OAR dose constraint violation (48% vs 0%, P < .01). ConclusionsSingle-fraction MRI-guided SABR is a dosimetrically feasible treatment for oligometastases that allows for on-table adaptation to avoid OAR dose constraint violations, but this method requires clinical validation.

Estimation of planning organ at risk volumes for ocular structures in dogs undergoing three-dimensional image-guided periocular radiotherapy with rigid bite block immobilization.

Planning organ at risk volume (PRV) estimates have been reported as methods for sparing organs at risk (OARs) during radiation therapy, especially for hypofractioned and/or dose‐escalated protocols. The objectives of this retrospective, analytical, observational study were to evaluate peri‐ocular OAR shifts and derive PRVs in a sample of dogs undergoing radiation therapy for periocular tumors. Inclusion criteria were as follows: dogs irradiated for periocular tumors, with 3D‐image‐guidance and at least four cone‐beam CTs (CBCTs) used for position verification, and positioning in a rigid bite block immobilization device. Peri‐ocular OARs were contoured on each CBCT and the systematic and random error of the shifts in relation to the planning CT position computed. The formula 1.3×Σ+0.5xσ was used to generate a PRV of each OAR in the dorsoventral, mediolateral, and craniocaudal axis. A total of 30 dogs were sampled, with 450 OARs contoured, and 2145 shifts assessed. The PRV expansion was qualitatively different for each organ (1‐4 mm for the dorsoventral and 1‐2 mm for the mediolateral and craniocaudal axes). Maximal PRV expansion was ≤4 mm and directional for the majority; most pronounced for corneas and retinas. Findings from the current study may help improve awareness of and minimization of radiation dose in peri‐ocular OARs for future canine patients. Because some OARs were difficult to visualize on CBCTs and/ or to delineate on the planning CT, authors recommend that PRV estimates be institution‐specific and applied with caution.

The Dancing Cord: Inherent Spinal Cord Motion and Its Effect on Cord Dose in Spine Stereotactic Body Radiation Therapy

BACKGROUNDSpinal cord dose limits are critically important for the safe practice of spine stereotactic body radiotherapy (SBRT). However, the effect of inherent spinal cord motion on cord dose in SBRT is unknown.OBJECTIVETo assess the effects of cord motion on spinal cord dose in SBRT.METHODSDynamic balanced fast field echo (BFFE) magnetic resonance imaging (MRI) was obtained in 21 spine metastasis patients treated with SBRT. Planning computed tomography (CT), conventional static T2-weighted MRI, BFFE MRI, and dose planning data were coregistered. Spinal cord from the dynamic BFFE images (corddyn) was compared with the T2-weighted MRI (cordstat) to analyze motion of corddyn beyond the cordstat (Dice coefficient, Jaccard index), and beyond cordstat with added planning organ at risk volume (PRV) margins. Cord dose was compared between cordstat, and corddyn (Wilcoxon signed-rank test).RESULTSDice coefficient (0.70-0.95, median 0.87) and Jaccard index (0.54-0.90, median 0.77) demonstrated motion of corddyn beyond cordstat. In 62% of the patients (13/21), the dose to corddyn exceeded that of cordstat by 0.6% to 13.8% (median 4.3%). The corddyn spatially excursed outside the 1-mm PRV margin of cordstat in 9 patients (43%); among these dose to corddyn exceeded dose to cordstat >+ 1-mm PRV margin in 78% of the patients (7/9). Corddyn did not excurse outside the 1.5-mm or 2-mm PRV cord cordstat margin.CONCLUSIONSpinal cord motion may contribute to increases in radiation dose to the cord from SBRT for spine metastasis. A PRV margin of at least 1.5 to 2 mm surrounding the cord should be strongly considered to account for inherent spinal cord motion.

Long Term Clinical Outcomes Of Multi-Level Spinal SBRT For Vertebral Metastases

Currently, sSBRT is commonly limited to solitary, 2 contiguous or 3 non-contiguous vertebral levels because of concerns regarding setup accuracy, efficacy, and toxicity when 2-3 non-contiguous levels are treated. There is, however, a paucity of data regarding the clinical outcomes of multilevel sSBRT. LC and toxicity are particularly important endpoints to ensure that standard clinical target volume (CTV), planning target volume (PTV), and planning organ-at-risk volume (PRV) expansions are appropriate in the multilevel setting. We sought to compare efficacy and toxicities of single- vs multilevel (≥2-5) treatment in a cohort of patients with malignant spinal tumors. Radioresistant histologies, Bilsky grade 0 to 1 epidural spinal cord compression,5 and a life expectancy >6 mo. are treated by SBRT. Single level and Multi-level spinal SBRT are defined as sSBRT delivered to a malignant lesion spanning single and ≥2 contiguous vertebral levels. All patients underwent treatment rigid immobilization for C1-D4 targets / body fix immobilization for D5 and below targets. For intact cases, GTVs were delineated using the registered T1-weighted precontrast and postcontrast MRI sequences, with reference to additional diagnostic studies (PET and perfusion MRI). CTVs were expanded 2mm circumferentially to create PTVs, with the goal of≥95% PTV coverage with ≥100% of the prescription dose. For cord delineation done on either CT myelography / T2-weighted MRI fused to the planning CT with 1-mm cord PRV. The same PTV and PRV expansions were used regardless of surgical status or number of treated vertebral levels. All patients underwent multi-isocenter VMAT planning using dual arcs and treatment delivered on C-Arm Linac using 6 DOF robotics with pretreatment, Intrafraction and posttreatment imaging. We analyzed consecutive cases of sSBRT treated from 2013 to 2017. Time-to event outcomes for single-level and multilevel cases were compared using mixed effect Cox models and differences in toxicity rates were evaluated using linear mixed effect models. All models incorporate a patient-level random intercept to account for any within patient. There were 101 single-level and 84 multilevel sSBRT cases (2-5 continuous vertebral levels). One-year LC was 95% vs 85%, respectively. After adjusting for baseline covariates, dose delivered, and accounting for within-patient correlation, there was no significant difference in time to local failure (hazard ratio, HR 1.79 [0.59-5.4]; P = .30). Pain improved in 83.5% of the 139 initially symptomatic tumors. There were no significant differences in grade 2+ acute or late toxicities between single-level and multilevel sSBRT Multilevel sSBRT provides high rates of LC, similar to single-level treatment, without need for larger planning volume margins. Efforts to improve prognostication and case selection for multilevel sSBRT are warranted to ensure that the benefits of improved LC over palliative radiation are justified.

Impact of tumor volume enlargement after induction chemotherapy on subsequent radiotherapy in locally advanced nasopharyngeal carcinoma: A propensity-score matching analysis.

A small proportion of nasopharyngeal carcinoma (NPC) patients show resistance to induction chemotherapy (IC). This study sought to investigate the impact of tumor volume enlargement after IC on the dosimetric parameters of subsequent radiotherapy. The records of a total of 240 locally advanced NPC patients who received IC followed by concurrent chemoradiotherapy were retrospectively reviewed. Patients with a tumor volume enlargement of ≥10% and patients with a tumor volume reduction of ≥10% after induction chemotherapy were classified as the enlargement group and the control group, respectively. The dosimetric parameters of the planning target volumes (PTVs) and the organs at risk (OARs) were compared between the matched groups after propensity score matching (PSM). For the gross tumor volume of nasopharynx (GTVnx), 21 patients and 127 patients were classified as the enlargement group and the control group, respectively. After matching, 20 sub‐pairs of 40 patients were generated in the post‐PSM cohort. The GTVnx enlargement group exhibited no significant disadvantages in all of the dosimetric parameters, except in the planning organ‐at‐risk volume (PRV) of contralateral lens (Dmax, 722 cGy vs. 634 cGy, p = 0.041). For the gross tumor volume of lymph nodes (GTVnd), 44 patients and 144 patients were classified as the enlargement group and the control group, respectively. After matching, 39 sub‐pairs of 78 patients were generated in the post‐PSM cohort. The GTVnd enlargement group exhibited no significant disadvantages in all of the dosimetric parameters. Univariate and multivariate analyses showed that the enlargement of GTVnx and the enlargement of GTVnd were not independently associated with any of the dosimetric parameters. A tumor volume enlargement of ≥10% in GTVnx or GTVnd after induction chemotherapy has no significant impact on the dosimetric parameters of subsequent radiotherapy in locally advanced NPC.

Dosimetric effects of dose calculation grid size on the epidural space dose

Introduction: The epidural disease progression is the most common pattern of failure after spine stereotactic body radiotherapy. The aim of this study was to clarify the effect of the dose calculation grid size (CGS) during volumetric modulated arc therapy planning on the dose to the epidural space target. Materials and Methods: In the planning, the volume obtained by subtracting the planning organ at risk volume (PRV) of the spinal cord and/or cauda equina from the planning target volume (PTV) was defined as the PTVeval. First, we compared the epidural space dose that overlapped with the PTVeval at dose CGSs of 1 mm and 2 mm. Next, we compared the dose that can be given, according to the isotropic distance from the PRV of the spinal cord and/ or cauda equina at dose CGSs of 1 mm and 2 mm. Results: The dose to the epidural space overlapping with the PTVeval was significantly larger at the dose CGS of 1 mm (60 to 80 cGy, 3% of the prescription dose) than at the dose CGS of 2 mm (p < 0.01). In addition, compared with the dose CGS of 2 mm, the dose CGS of 1 mm provided a larger dose to 95% of the volume in the regions where the PTVeval overlapped at isotropic distances of 0 to < 1, 1 to 2, 2 to 3, 3 to 4, and 4 to 5 mm from the PRV of the spinal cord and/or cauda equina. Conclusions: During spine stereotactic body radiotherapy by volumetric modulated arc therapy, the dose CGS of 1 mm improved the dose calculation accuracy and increased the dose to the epidural space target compared with the dose CGS of 2 mm.

The urethral position may shift due to urethral catheter placement in the treatment planning for prostate radiation therapy

PurposeTo determine the best method to contour the planning organ at risk volume (PRV) for the urethra, this study aimed to investigate the displacement of a Foley catheter in the urethra with a soft and thin guide-wire.MethodsFor each patient, the study used two sets of computed tomography (CT) images for radiation treatment planning (RT-CT): (1) set with a Foley urethral catheter (4.0 mm diameter) plus a guide-wire (0.46 mm diameter) in the first RT-CT and (2) set with a guide-wire alone in the second CT recorded 2 min after the first RT-CT. Using three fiducial markers in the prostate for image fusion, the displacement between the catheter and the guide-wire in the prostatic urethra was calculated. In 155 consecutive patients treated between 2011 and 2017, 5531 slices of RT-CT were evaluated.ResultsAssuming that ≥3.0 mm of difference between the catheter and the guide-wire position was a significant displacement, the urethra with the catheter was displaced significantly from the urethra with the guide-wire alone in > 20% of the RT-CT slices in 23.2% (36/155) of the patients. The number of patients who showed ≥3.0 mm anterior displacement with the catheter in ≥20% RT-CT slices was significantly larger at the superior segment (38/155) than at the middle (14/155) and inferior segments (18/155) of the prostatic urethra (p < 0.0167).ConclusionsThe urethral position with a Foley catheter is different from the urethral position with a thin and soft guide-wire in a significant proportion of the patients. This should be taken into account for the PRV of the urethra to ensure precise radiotherapy such as in urethra-sparing radiotherapy.

A Treatment Planning Study of Moderately Hypofractionated Intensity-Modulated Proton Therapy (IMPT) to the Prostate and Pelvic Combined with Extremely Hypofractionated IMPT Boost to Prostate with Urethral Dose Reduction for High-Risk Prostate Cancer

Moderately hypofractionated radiotherapy (RT) can be considered for all prostate cancer (PCa) patients while extremely hypofractionated RT is only recommended for low-intermediate risk PCa. Dose escalation is associated with improved biochemical outcomes for patients with high risk PCa. Currently intensity modulated proton therapy (IMPT) holds the potential to improve dose delivery and spare nontarget tissues. The purpose of this study was to explore the feasibility of moderately hypofractionated IMPT combined with extremely hypofractionated IMPT boost to prostate with urethral dose reduction for high risk PCa. We retrospectively reviewed the planning CT images of 3 PCa patients with a urethral catheter (4.0 mm dia.) treated with photon therapy and made the IMPT plan for these patients. The contours of the prostate were defined as the CTVp. CTVsv included proximal 2cm of the seminal vesicles. CTVpelvic included the pelvic regional lymph nodes. PTV was determined by a 3D expansion of the CTV with the addition of a 5-mm margin except for posterior direction to avoid the expansion to rectum. The urethra as an OAR was contoured in 2 mm diameter. A margin of 2 mm was applied to the urethra to determine the planning organ at risk volume (PRV). In the first course of the plan, A 8GyE boost was given in one fraction to PTVp subtract urethralPRV(PTVp-u). In the second course, the electron density of urethral was defined as same as prostate. A total of 67.5 GyE in 25 fractions (2.7 GyE/fraction) were delivered to the PTVp(whole prostate gland including the urethra). Prescription dose for PTVsv and PTVpelvic were 60GyE (2.4GyE/fraction) and 47.5 GyE(1.9GyE/fraction) in 25 fractions, respectively. A dose constraint of V70Gy < 10% was applied to the urethralPRV (6 mm dia.). Patients were treated with 2 lateral-opposed (LAT) fields. An additional 3.5% of proximal and distal water equivalent thickness plus 2 mm was added to the PTV to account for beam range uncertainty. In the combined plan, target volume coverage of 70GyE to the PTVp was 95.7±1.3%. Coverage of dose prescription of the PTVsv and PTVpelvic all reached 95%. In addition, a total dose of 78GyE covered more than 95% of the external region of 1cm expansion of the urethralPRV for all these patients. Meanwhile, the V70Gy of the urethralPRV was as low as 1.7±1.3%. The V70Gy, V60Gy, V50Gy of the rectum were 2.9±1.7%, 11.27±2.5% and 8.1±0.9%. The V50Gy of the bladder was only 8.1±0.9%. The V50Gy of the left and right femoral were 1.5±0.8% and 1.4±0.8%, respectively. For high risk PCa who received prostate and pelvic irradiation, moderately hypofractionated irradiation combined with extremely hypofractionated IMPT boost to prostate using IMPT technique could bring higher biological equivalent dose and excellently protect the urethral.

Dosimetric Effect of Calculation Grid Size on Epidural Space in Spine Stereotactic Body Radiotherapy Using Volumetric Modulated Arc Therapy

To perform spine stereotactic body radiotherapy (SBRT), it is important to spare the dose to the spinal cord to prevent radiation myelopathy. Conversely, we should keep sufficient dose to the target volume in the epidural space neighboring the spinal cord because the epidural space is reported as the most common site of recurrence after spine SBRT. Especially for re-irradiation, the dose constraint of the spinal cord is severer than first time radiation and it is more difficult to keep the dose in epidural space high. With the development of computer technology in recent year, a finer calculation grid size (CGS) has come to be used in dose optimization of volumetric modulated arc therapy (VMAT). However, in the spinal SBRT using VMAT, the effect of CGS on the dose to the epidural space has not been elucidated. The aim of this study was to determine the dosimetric effect on the target in the epidural space and spinal cord of the CGS in dose optimization of VMAT. This study was a single center retrospective dosimetric study of 9 patients previously treated for the spinal metastasis at our institution. Planning target volume (PTV) and planning organ at risk volume (PRV) for spinal cord were defined by adding isotropic margins of 2 mm for clinical target volume (CTV) and of 1.5 mm for the spinal cord, respectively. In addition, kidneys, trachea, and esophagus around the PTV were defined as the organ at risks. The prescribed dose was 24 Gy in 2 fractions for the volume obtained by subtracting the PRV of the spinal cord from the PTV. The dose tolerance for PRV of the spinal cord was 12.2 Gy. The following dose parameters were compared between the CGSs of 1 mm and 2 mm in dose optimization of VMAT: D99%, D98%, D95%, D50% for the PTV in the epidural space, and D0.035cc for the PRV of the spinal cord. The dose parameters for the CGS of 2 mm were evaluated after resampling to 1 mm without the change of fluence per delivery angle. Regarding the CGSs of 1 mm and 2 mm, D99%, D98%, D95%, D50% for the PTV in the epidural space were 10.1±1.3 Gy, 10.7±1.3 Gy, 11.7±1.5 Gy, 18.6±4.6 Gy and 9.6±1.1 Gy, 10.1±1.1 Gy, 11.0±1.3 Gy, 17.8±4.8 Gy, respectively. The CGS of 2 mm showed dose decrease of approximately 0.7 Gy for all parameters (p ˂0.01). The values of D0.035cc for the PRV of the spinal cord were 12.1±0.0 Gy and 11.4±0.2 Gy, respectively. The value obtained by the CGS of 2 mm decreased approximately 0.7 Gy (p <0.001) compared to that of 1 mm. In addition, visual evaluation of the difference image obtained by subtracting the dose distribution of the CGS of 1 mm from that of 2 mm showed the decrease of the PTV dose in the epidural space. For the epidural space where the most frequent recurrence occurs in the spinal SBRT, the dosimetric effect of the CGS in dose optimization of VMAT were investigated. In our analysis, the CGS of 2 mm underestimates the dose to the target in the epidural space, while the CGS of 1 mm would be more accurate for calculation of the target in the epidural space.

Dose-response relationship and normal-tissue complication probability of conductive hearing loss in patients undergoing head-and-neck or cranial radiotherapy: A prospective study including 70 ears

PurposeHead-and-neck (H&N) and cranial radiotherapy may cause hearing loss. Little has been published on the dose-response relationship and normal-tissue complication probability (NTCP) of the conductive subtype of hearing loss. The aims were to observe the incidence of hearing loss in patients undergoing non-intensity-modulated H&N or cranial radiotherapy, obtain the relationship between dose and conductive hearing loss (CHL) and test the current Lyman-Kutcher-Burman (LKB) NTCP model parameters. MethodsThe dose-response in the peripheral auditory system (PAS) of 35 patients (70 ears) was prospectively studied using mean dose and the current LKB model parameters. A wide dose range was obtained by conducting the study at a clinic without advanced treatment techniques. The patients underwent routine external-beam treatments following 3D treatment planning. Hearing status was evaluated by pure-tone audiometry one day before the start and one day and 30 days after the end of radiotherapy. ResultsNineteen ears (27%) experienced hearing loss. Sixteen (23%) had CHL and three (4%) the sensorineural subtype. On average, mean doses of the PAS structures and V95%, V40Gy and V30Gy volumes of the middle-ear planning-organ-at-risk volume (PRV) were significantly greater in ears that suffered CHL. The modelled 50% NTCP of CHL occurred at approximately 30–40 Gy mean dose to middle ear planning organ-at-risk volume. ConclusionsIncidence of conductive hearing loss in non-intensity-modulated radiotherapy of H&N and brain can be significant. CHL exhibits a dose-effect. This suggests that the PAS should be considered in treatment plan optimization. The LKB NTCP model was reasonably accurate but modifications are indicated.

(OA43) Delineation of a Cardiac PRV Using Real-Time Magnetic Resonance Imaging for Cardiac Protection in Thoracic and Breast Radiation Therapy

Historically, increased cardiac radiation dose has been associated with late cardiotoxicity events in patients with thoracic and breast malignancies. Recently, a prospective trial also revealed correlation between cardiac dose and early toxicity, including reduced overall survival in patients receiving curative-intent treatment. While breath-hold techniques reduce motion, they cannot account for cardiac cycle motion. We conducted a prospective cine magnetic resonance imaging (cMRI) study and applied an established scale-invariant feature transform (SIFT)-based algorithm to track and evaluate heart motion. We hypothesized that cMRI could be used to define a cardiac planning organ-at-risk volume (PRV) for routine application in radiation planning to improve cardiac protection. Imaging was performed on a 1.5 Tesla MR scanner (Philips Ingenia 1.5T MR System). 16 acquisitions were obtained per subject using a balanced-steady-state gradient echo sequence. Single-plane cMRI was performed in four sequential sagittal and four sequential coronal planes, spanning the heart in equidistant left-right (LR) and anterior-posterior (AP) intervals. Free-breathing (FB) and deep-inspiratory-breath-hold (DIBH) acquisitions were performed at each plane. In-plane cardiac motion was assessed on all image sets for each subject. The reference image and each image within the corresponding acquisition image set were registered via a previously published technique that describes pixels by high-dimensional descriptors, incorporating nearby intensity gradients rather than pixel intensity alone. Each descriptor, defined by the scale-invariant feature transform (SIFT) algorithm, is a set of histograms of intensity gradients within sub-regions surrounding a given pixel. Pixel trajectories were then identified by minimizing an objective function to locate best-matching descriptors between the reference image and each image within an acquisition. Subject-specific pixel motion ranges were derived by averaging slice-by-slice motion of each pixel to yield mean values for AP, LR, and superior-inferior (SI) directions. For each subject, average maximum range of pixel displacement and average pixel-based interquartile range (IQR) of displacement were calculated. These values were then utilized and averaged across the cohort to calculate planning organ-at-risk volume (PRV) expansions at FB and DIBH. 20 subjects were enrolled with median age 34.5 years (range 20-78), BMI 23.75 (range 17.7-33.3), and height 64 inches (range 57-69). A total of 3,120 image frames were collected per patient in coronal and sagittal planes, at DIBH and FB, with 62,400 frames analyzed across the cohort. SIFT methodology was successfully implemented in all patients to track motion. The cohort average of maximum motion ranges comprised PRV margin expansions of 13.7±1.8mm SI, 6.9±1.4mm AP, and 7.7±1.2mm LR plane at FB; expansions for DIBH were 7.1±1.5mm SI, 5.1±1.4mm AP, and 5.6±1.3mm LR. IQR-based PRVs, calculated to encompass the most frequent range of cardiac displacement, comprised 3.7±0.7mm SI, 1.2±0.4mm AP, and 1.4±0.3mm LR at FB and 1.8±0.6mm SI, 1.0±0.3mm AP, and 1.3±0.4mm LR at DIBH. IQR-based PRV expansions were then successfully applied for both locally-advanced lung cancer and breast cancer treatment planning. We successfully utilized SIFT-based motion-tracking for analysis of 62,400 prospectively gathered cine MR image frames to identify and apply a cardiac PRV for treatment planning to improve cardiac protection in breast and thoracic radiation.

Evaluation of MLC leaf transmission on IMRT treatment plan quality of patients with advanced lung cancer

The purpose of this paper was to evaluate the impact of leaf treatment of multileaf collimator (MLC) in plan quality of intensity-modulated radiotherapy (IMRT) of patients with advanced lung cancer. Five MLCs with different leaf transmissions (0.01%, 0.5%, 1.2%, 1.8%, and 3%) were configured for an accelerator in a treatment planning system. Correspondingly, 5 treatment plans with the same optimization setting were created and evaluated quantitatively for each patient (11 patients total) who was diagnosed with advanced lung cancer. All of the 5 plans for each patient met the dose requirement for the planning treatment volumes (PTVs) and had similar target dose homogeneity and conformity. On average, the doses to selected organs were as follows: (1) V5, V20, and the mean dose of total lung; (2) the maximum and mean dose to spinal cord planning organ-at-risk volume (PRV); and (3) V30 and V40 of heart, decreased slightly when MLC transmission was decreased, but with no statistical differences. There is a clear grouping of plans having total quality score (SD) value, which is used to evaluate plan quality: (1) more than 1 (patient nos. 1 to 3, 5, and 8), and more than 2.5 (patient no. 6); (2) less than 1 (patient nos. 7 and 10); (3) around 1 (patient nos. 4, 9, and 11). As MLC transmission increased, overall SD values increased as well and plan dose requirement was harder to meet. The clinical requirements were violated increasingly as MLC transmission became large. Total SD with and without normal tissue (NT) showed similar results, with no statistically significant differences. Therefore, decrease of MLC transmission did have minimum impact on plan, and it improved target coverage and reduced normal tissue radiation slightly, with no statistical significance. Plan quality could not be significantly improved by MLC transmission reduction. However, lower MLC transmission may have advantages on lung sparing to low- and intermediate-dose exposure. Besides conventional fraction, hyperfraction, or stereotactic body radiotherapy (SBRT), the reduction on lung sparing is still essential because it is highly relevant to radiation pneumonitis (RP). It has potential to diminish incidence of RP and improve patient's quality of life after irradiation with lowered MLC transmission.

Dose escalation by image-guided intensity-modulated radiotherapy leads to an increase in pain relief for spinal metastases: a comparison study with a regimen of 30 Gy in 10 fractions.

PurposeUnder the existing condition that the optimum radiotherapy regimen for spinal metastases is controversial, this study investigates the benefits of dose escalation by image-guided intensity-modulated radiotherapy (IG-IMRT) with 60–66 Gy in 20–30 fractions for spinal metastases.ResultsIn the dose-escalation group, each D50 of planning gross tumor volume (PGTV) was above 60 Gy and each Dmax of spinal cord planning organ at risk volume (PRV) was below 48 Gy. The median biological effective dose (BED) of Dmax of spinal cord was lower in the dose-escalation group compared with that in the 30-Gy group (69.70 Gy vs. 83.16 Gy, p < 0.001). After one month and three months of the radiotherapy, pain responses were better in the dose-escalation group than those in the 30-Gy group (p = 0.005 and p = 0.024), and the complete pain relief rates were respectively 73.69% and 34.29% (p = 0.006), 73.69% and 41.38% (p = 0.028) in two compared groups. In the dose-escalation group, there is a trend of a longer duration of pain relief, a longer overall survival and a lower incidence of acute radiation toxicities. No late radiation toxicities were observed in both groups.Materials and MethodsDosimetric parameters and clinical outcomes, including pain response, duration of pain relief, radiation toxicities and overall survival, were compared among twenty-five metastatic spinal lesions irradiated with the dose-escalation regimen and among forty-four lesions treated with the 30-Gy regimen.ConclusionsConventionally-fractionated IG-IMRT for spinal metastases could escalate dose to the vertebral lesions while sparing the spinal cord, achieving a better pain relief without increasing radiation complications.

Proposed expansion margins for planning organ at risk volume for lenses during radiation therapy of the nasal cavity in dogs and cats.

Radiation therapy protocols for the feline or canine nasal cavity can damage epithelial cells of the posterior pole of the lens and lead to the development of cataracts. Aims of this retrospective, descriptive study were to calculate movements of the lens during radiation therapy of the nasal cavity in a sample of cats and dogs, and to propose species-specific expansion margins for planning organ at risk volume (PRV) to minimize radiation doses to the lens. All included patients were immobilized with an indexed bite block and positioned in a vacuum positioning cushion for head irradiation. On-board cone beam CT (CBCT) imaging was used for patient alignment. Both ocular lenses were contoured on the therapeutic CBCTs. Coregistration (fusion) between the planning CT and CBCTs was used to measure the movements of the lens. Two measurements were made: the differences between the centroid point of each lens as well as the displacement of the coregistrations. A total of 496 different observations were recorded from 14 cats and 52 dogs. Using the displacement results, we calculated how often the lens would be within the lens-PRV contour. We proposed that an optimal expansion margin from the lens volume of 2 mm in cats and 3 mm in dogs may be necessary in generating PRV expansion for the lens. From our results, we expect the lens would therefore be within these proposed PRV expansions in 92% of the feline measurements and 95% of the canine measurements.

Consensus Contouring Guidelines for Postoperative Stereotactic Body Radiation Therapy for Metastatic Solid Tumor Malignancies to the Spine

Todevelop consensus contouring guidelines for postoperative stereotactic body radiation therapy (SBRT) for spinal metastases. Ten spine SBRT specialists representing 10 international centers independently contoured the clinical target volume (CTV), planning target volume (PTV), spinal cord, and spinal cord planning organ at risk volume (PRV)for 10 representative clinical scenarios in postoperative spine SBRT for metastatic solid tumor malignancies. Contours were imported into the Computational Environment for Radiotherapy Research. Agreement between physicians was calculated with an expectation minimization algorithm using simultaneous truth and performance level estimation with κ statistics. Target volume definition guidelines were established by finding optimized confidence level consensus contours using histogram agreement analyses. Nine expert radiation oncologists and 1 neurosurgeon completed contours for all 10 cases. The mean sensitivity and specificity were 0.79 (range, 0.71-0.89) and 0.94 (range, 0.90-0.99) for the CTV and 0.79 (range, 0.70-0.95) and 0.92 (range, 0.87-0.99) for the PTV), respectively. Mean κ agreement, which demonstrates the probability that contours agree by chance alone, was 0.58 (range, 0.43-0.70) for CTV and 0.58 (range, 0.37-0.76) for PTV (P<.001 for all cases). Optimized consensus contours were established for all patients with 80% confidence interval. Recommendations for CTV include treatment of the entire preoperative extent of bony and epidural disease, plus immediately adjacent bony anatomic compartments at risk of microscopic disease extension. In particular, a "donut-shaped" CTV was consistently applied in cases of preoperative circumferential epidural extension, regardless of extent of residual epidural extension. Otherwise more conformal anatomic-based CTVs were determined and described. Spinal instrumentation was consistently excluded from the CTV. We provide consensus contouring guidelines for common scenarios in postoperative SBRT for spinal metastases. These consensus guidelines are subject to clinical validation.