Evaluation of Diaphragm Position Variations During Proton Therapy for Pediatric Patients With Neuroblastoma.

Background To evaluate the respiratory-induced intrafractional diaphragm motion and interfractional diaphragm displacement in pediatric patients with neuroblastoma (NBL). Materials and methods Ten pediatric patients with a mean age of 4.5 years (range: 1.8-8.7 years) with abdominal NBL treated with proton therapy (PT) have been evaluated. Intrafractional motion and interfractional displacement have been analyzed by using cine radiography and orthogonal X-ray images, respectively. In each case, the cranio-caudal positions of the diaphragm have been measured as an index. This study has investigated the possible correlations between intrafractional diaphragm motion and height. Additionally, interfractional displacement and its time trend during the treatment course have been analyzed. Results The average right and left diaphragm intrafractional motions of 8.3 mm (range: 4.4-11.5 mm) and 6.4 mm (range: 2.2-11.8 mm) were observed, respectively; however, no significant correlation has been observed with height. An interfractional displacement of 5 mm or more has been observed in 20 out of 152 fractions (13%). The average absolute value of the interfractional displacement was 2.5 mm (range: 0-8.6 mm). Interfractional displacement did not show a peculiar tendency throughout the treatment period. Conclusions It was suggested that respiratory-induced diaphragm position variation in children varies greatly among individuals, and accurately estimating it based on height is difficult. Thus, these individual evaluations are considered indispensable.

Inter-fractional error and intra-fractional motion of prostate and dosimetry comparisons of patient position registrations with versus without fiducial markers during treatment with carbon-ion radiotherapy.

A few reports have discussed the influence of inter-fractional position error and intra-fractional motion on dose distribution, particularly regarding a spread-out Bragg peak. We investigated inter-fractional and intra-fractional prostate position error by monitoring fiducial marker positions. In 2020, data from 15 patients with prostate cancer who received carbon-ion beam radiotherapy (CIRT) with gold markers were investigated. We checked marker positions before and during irradiation to calculate the inter-fractional positioning and intra-fractional movement and evaluated the CIRT dose distribution by adjusting the planning beam isocenter and clinical target volume (CTV) position. We compared the CTV dose coverages (CTV receiving 95% [V95%] or 98% [V98%] of the prescribed dose) between skeletal and fiducial matching irradiation on the treatment planning system. For inter-fractional error, the mean distance between the marker position in the planning images and that in a patient starting irradiation with skeletal matching was 1.49 ± 1.11 mm (95th percentile = 1.85 mm). The 95th percentile (maximum) values of the intra-fractional movement were 0.79 mm (2.31 mm), 1.17 mm (2.48 mm), 1.88 mm (4.01 mm), 1.23 mm (3.00 mm), and 2.09 mm (8.46 mm) along the lateral, inferior, superior, dorsal, and ventral axes, respectively. The mean V95% and V98% were 98.2% and 96.2% for the skeletal matching plan and 99.5% and 96.8% for the fiducial matching plan, respectively. Fiducial matching irradiation improved the CTV dose coverage compared with skeletal matching irradiation for CIRT for prostate cancer.

Pelvic target volume inter-fractional motion during radiotherapy for cervical cancer with daily iterative cone beam computed tomography.

BACKGROUND: Tumor regression and organ movements indicate that a large margin is used to ensure target volume coverage during radiotherapy. This study aimed to quantify inter-fractional movements of the uterus and cervix in patients with cervical cancer undergoing radiotherapy and to evaluate the clinical target volume (CTV) coverage. METHODS: This study analyzed 303 iterative cone beam computed tomography (iCBCT) scans from 15 cervical cancer patients undergoing external beam radiotherapy. CTVs of the uterus (CTV-U) and cervix (CTV-C) contours were delineated based on each iCBCT image. CTV-U encompassed the uterus, while CTV-C included the cervix, vagina, and adjacent parametrial regions. Compared with the planning CTV, the movement of CTV-U and CTV-C in the anterior-posterior, superior-inferior, and lateral directions between iCBCT scans was measured. Uniform expansions were applied to the planning CTV to assess target coverage. RESULTS: The motion (mean ± standard deviation) in the CTV-U position was 8.3 ± 4.1 mm in the left, 9.8 ± 4.4 mm in the right, 12.6 ± 4.0 mm in the anterior, 8.8 ± 5.1 mm in the posterior, 5.7 ± 5.4 mm in the superior, and 3.0 ± 3.2 mm in the inferior direction. The mean CTV-C displacement was 7.3 ± 3.2 mm in the left, 8.6 ± 3.8 mm in the right, 9.0 ± 6.1 mm in the anterior, 8.4 ± 3.6 mm in the posterior, 5.0 ± 5.0 mm in the superior, and 3.0 ± 2.5 mm in the inferior direction. Compared with the other tumor (T) stages, CTV-U and CTV-C motion in stage T1 was larger. A uniform CTV planning treatment volume margin of 15 mm failed to encompass the CTV-U and CTV-C in 11.1% and 2.2% of all fractions, respectively. The mean volume change of CTV-U and CTV-C were 150% and 51%, respectively, compared with the planning CTV. CONCLUSIONS: Movements of the uterine corpus are larger than those of the cervix. The likelihood of missing the CTV is significantly increased due to inter-fractional motion when utilizing traditional planning margins. Early T stage may require larger margins. Personal radiotherapy margining is needed to improve treatment accuracy.

Comparing Efficacy Between Robust and PTV Margin-based Optimizations for Interfractional Anatomical Variations in Prostate Tomotherapy.

BACKGROUND/AIM: Interfractional anatomical variations cause considerable differences between planned and actual radiotherapy doses. This study aimed to investigate the efficacy of robust and planning target volume (PTV) margin-based optimizations for the anatomical variations in helical tomotherapy for prostate cancer. PATIENTS AND METHODS: Ten patients underwent treatment-planning kilovolt computed tomography (kVCT) and daily megavolt computed tomography (MVCT). Two types of nominal plans, with a prescription of 60 Gy/20 fractions, were created using robust and PTV margin-based optimizations on kVCT for each patient. Subsequently, the daily estimated doses were recalculated using nominal plans, and all available MVCTs modified the daily patient-setup errors. Due to the difference in dose calculation accuracy between kVCT and MVCT, three scenarios with dose corrections of 1, 2, and 3% were considered in the recalculation process. The dosimetric metrics, including target coverage with the prescription dose, Paddick's conformity index, homogeneity index, and mean dose to the rectum, were analyzed. RESULTS: A dosimetric comparison of the nominal plans demonstrated that the robust plans had better dose conformity, lower target coverage, and dose homogeneity than the PTV plans. In the daily estimated doses of any dose-corrected scenario, the target coverage and dose sparing to the rectum in the robust plans were significantly higher than those in the PTV plans, whereas dose conformity and homogeneity were identical to those of the nominal case. CONCLUSION: Robust optimization is recommended as it accounts for anatomical variations during treatment regarding target coverage in helical tomotherapy plans for prostate cancer.

Urethral identification using three-dimensional magnetic resonance imaging and interfraction urethral motion evaluation for prostate stereotactic body radiotherapy.

Prostatic urethra identification is crucial in prostate stereotactic body radiotherapy (SBRT) to reduce the risk of urinary toxicity. Although computed tomography (CT) with a catheter is commonly employed, it is invasive, and catheter placement may displace the urethral position, resulting in possible planning inaccuracies. However, magnetic resonance imaging (MRI) can overcome these weaknesses. Accurate urethral identification and minimal daily variation could ensure a highly accurate SBRT. In this study, we investigated the usefulness of a three-dimensional (3D) T2-weighted (T2W) sequence for urethral identification, and the interfractional motion of the prostatic urethra on CT with a catheter and MRI without a catheter for implementing noninvasive SBRT. Thirty-two patients were divided into three groups. The first group underwent MRI without a catheter to evaluate urethral identification by two-dimensional (2D)- and 3D-T2W sequences using mean slice-wise Hausdorff distance (MSHD) and Dice similarity coefficient (DSC) of the contouring by two operators and using visual assessment. The second group provided 3-day MRI data without a catheter using 3D-T2W, and the third provided 3-day CT data with a catheter to evaluate the interfractional motion using MSHD, DSC, and displacement distance (Dd). The MSHD and DSC for the interoperator variability in urethral identification and visual assessment were superior in 3D-T2W than in 2D-T2W. Regarding interfractional motion, the Dd value for prostatic urethra was smaller in MRI than in CT. These findings indicate that the 3D-T2W yielded adequate prostatic urethral identification, and catheter-free MRI resulted in less interfractional motion, suggesting that 3D-T2W MRI without a catheter is a feasible noninvasive approach to performing prostate SBRT.

Monitoring of Interfractional Proton Range Verification and Dosimetric Impact Based on Daily CBCT for Pediatric Patients with Pelvic Tumors.

(1) Background: Synthetic CT images of the pelvis were generated from daily CBCT images to monitor changes in water equivalent path length (WEPL) and determine the dosimetric impact of anatomy changes along the proton beam's path; (2) Methods: Ten pediatric patients with pelvic tumors treated using proton therapy with daily CBCT were included. The original planning CT was deformed to the same-day CBCT to generate synthetic CT images for WEPL comparison and dosimetric evaluation; (3) Results: WEPL changes of 20 proton fields at the distal edge of the CTV ranged from 0.1 to 12 mm with a median of 2.5 mm, and 75th percentile of 5.1 mm for (the original CT-rescanned CT) and ranged from 0.3 to 10.1 mm with a median of 2.45 mm and 75th percentile of 4.8 mm for (the original CT-synthetic CT). The dosimetric impact was due to proton range pullback or overshoot, which led to reduced coverage in CTV Dmin averaging 12.1% and 11.3% in the rescanned and synthetic CT verification plans, respectively; (4) Conclusions: The study demonstrated that synthetic CT generated by deforming the original planning CT to daily CBCT can be used to quantify proton range changes and predict adverse dosimetric scenarios without the need for excessive rescanned CT scans during large interfractional variations in adaptive proton therapy of pediatric pelvic tumors.

Assessment of dosimetric impact of interfractional 6D setup error in tongue cancer treated with IMRT and VMAT using daily kV-CBCT.

Background: This study aimed to evaluate the dosimetric influence of 6-dimensional (6D) interfractional setup error in tongue cancer treated with intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) using daily kilovoltage cone-beam computed tomography (kV-CBCT). Materials and methods: This retrospective study included 20 tongue cancer patients treated with IMRT (10), VMAT (10), and daily kV-CBCT image guidance. Interfraction 6D setup errors along the lateral, longitudinal, vertical, pitch, roll, and yaw axes were evaluated for 600 CBCTs. Structures in the planning CT were deformed to the CBCT using deformable registration. For each fraction, a reference CBCT structure set with no rotation error was created. The treatment plan was recalculated on the CBCTs with the rotation error (RError), translation error (TError), and translation plus rotation error (T+RError). For targets and organs at risk (OARs), the dosimetric impacts of RError, TError, and T+RError were evaluated without and with moderate correction of setup errors. Results: The maximum dose variation ΔD (%) for D98% in clinical target volumes (CTV): CTV-60, CTV-54, planning target volumes (PTV): PTV-60, and PTV-54 was -1.2%, -1.9%, -12.0%, and -12.3%, respectively, in the T+RError without setup error correction. The maximum ΔD (%) for D98% in CTV-60, CTV-54, PTV-60, and PTV-54 was -1.0%, -1.7%, -9.2%, and -9.5%, respectively, in the T+RError with moderate setup error correction. The dosimetric impact of interfractional 6D setup errors was statistically significant (p < 0.05) for D98% in CTV-60, CTV-54, PTV-60, and PTV-54. Conclusions: The uncorrected interfractional 6D setup errors could significantly impact the delivered dose to targets and OARs in tongue cancer. That emphasized the importance of daily 6D setup error correction in IMRT and VMAT.

Three-dimensional assessment of interfractional cervical and uterine motions using daily magnetic resonance images to determine margins and timing of replanning.

PURPOSE: This study was conducted to determine the margins and timing of replanning by assessing the daily interfractional cervical and uterine motions using magnetic resonance (MR) images. METHODS: Eleven patients with cervical cancer, who underwent intensity-modulated radiotherapy (IMRT) in 23-25 fractions, were considered in this study. The daily and reference MR images were converted into three-dimensional (3D) shape models. Patient-specific anisotropic margins were calculated from the proximal 95% of vertices located outside the surface of the reference model. Population-based margins were defined as the 90th percentile values of the patient-specific margins. The expanded volume of interest (expVOI) for the cervix and uterus was generated by expanding the reference model based on the population-based margin to calculate the coverage for daily deformable mesh models. For comparison, expVOIconv was generated using conventional margins: right (R), left (L), anterior (A), posterior (P), superior (S), and inferior (I) were (5, 5, 15, 15, 10, 10) and (10, 10, 20, 20, 15, 15) mm for the cervix and uterus, respectively. Subsequently, a replanning scenario was developed based on the cervical volume change. ExpVOIini and expVOIreplan were generated before and after replanning, respectively. RESULTS: Population-based margins were (R, L, A, P, S, I) of (7, 7, 11, 6, 11, 8) and (14, 13, 27, 19, 15, 21) mm for the cervix and uterus, respectively. The timing of replanning was found to be the 16th fraction, and the volume of expVOIreplan decreased by >30% compared to that of expVOIini . However, margins cannot be reduced to ensure equivalent coverage after replanning. CONCLUSION: We determined the margins and timing of replanning through detailed daily analysis. The margins of the cervix were smaller than conventional margins in some directions, while the margins of the uterus were larger in almost all directions. A margin equivalent to that at the initial planning was required for replanning.

Interfractional Liver Positional Motion Under Exhaled Breath Holding Based on Cone Beam Computed Tomography.

BACKGROUND/AIM: We measured interfractional liver positional motion in liver stereotactic body radiotherapy (SBRT) with exhaled breath holding (BH) based on kilovoltage (kV) cone-beam computed tomography (CBCT) images. PATIENTS AND METHODS: We collected 528 pre-treatment kV-CBCT images from 132 patients who underwent liver SBRT under exhaled BH using the Abches system, a non-electronic contact-based respiratory monitoring device, and analyzed them to investigate interfractional liver positional motion. Planning computed tomography (CT) scans were obtained using the Abches system when the patients were under exhaled BH. Translational 3-degree-of-freedom (DOF) soft-tissue-based image registration was performed using the kV-CBCT images under exhaled BH after 6-DOF vertebral bone image registration. Interfractional liver positional motions in the left-right (LR), anteroposterior (AP), and craniocaudal (CC) directions were defined based on the differences in the position of the liver relative to the vertebral bones. RESULTS: For all fractions, the absolute mean±standard deviation for the interfractional liver positional motion in the LR, AP, and CC directions was 0.7±1.0 mm, 1.0±1.5 mm, and 2.8±3.1 mm, respectively. The liver interfractional systematic/random positional motions in the LR, AP, and CC directions were 0.9/1.2 mm, 1.4/1.8 mm, and 2.9/3.9 mm, respectively. For all fractions, 100.0%, 98.3%, and 86.9% of the interfractional liver positional motions in the LR, AP, and CC directions, respectively, were less than 5 mm. CONCLUSION: CBCT-guided online correction should be used to correct interfractional liver positions errors present in liver SBRT with exhaled BH.

Effectiveness of CT-image guidance in proton therapy for liver cancer and the importance of daily dose monitoring for tumors and organs at risk.

BACKGROUND: It is important to have precise image guidance throughout proton therapy in order to take advantage of the therapy's physical selectivity. PURPOSE: We evaluated the effectiveness of computed tomography (CT)-image guidance in proton therapy for patients with hepatocellular carcinoma (HCC) by assessing daily proton dose distributions. The importance of daily CT image-guided registration and daily proton dose monitoring for tumors and organs at risk (OARs) was investigated. METHODS: A retrospective analysis was conducted using 570 sets of daily CT (dCT) images throughout whole treatment fractions for 38 HCC patients who underwent passive scattering proton therapy with either a 66 cobalt gray equivalent (GyE)/10 fractions (n = 19) or 76 GyE/20 fractions (n = 19) protocol. The actual daily delivered dose distributions were estimated by forward calculation using the dCT sets, their corresponding treatment plans, and the recorded daily couch correction information. We then evaluated the daily changes of the dose indices D99% , V30GyE , and Dmax for the tumor volumes, non-tumorous liver, and other OARs, that is, stomach, esophagus, duodenum, colon, respectively. Contours were created for all dCT sets. We validated the efficacy of the dCT-based tumor registrations (hereafter, "tumor registration") by comparing them with the bone registration and diaphragm registration as a simulation of the treatment based on the positioning using the conventional kV X-ray imaging. The dose distributions and the indices of three registrations were obtained by simulation using the same dCT sets. RESULTS: In the 66 GyE/10 fractions, the daily D99% value in both the tumor and diaphragm registrations agreed with the planned value with 3%-6% (SD), and the V30GyE value for the liver agreed within ±3%; the indices in the bone registration showed greater deterioration. Nevertheless, tumor-dose deterioration occurred in all registration methods for two cases due to daily changes of body shape and respiratory condition. In the 76 GyE/20 fractions, in particular for such a treatment that the dose constraints for the OARs have to be cared in the original planning, the daily D99% in the tumor registration was superior to that in the other registration (p < 0.001), indicating the effectiveness of the tumor registration. The dose constraints, set in the plan as the maximum dose for OARs (i.e., duodenum, stomach, colon, and esophagus) were maintained for 16 patients including seven treated with re-planning. For three patients, the daily Dmax increased gradually or changed randomly, resulting in an inter-fractional averaged Dmax higher than the constraints. The dose distribution would have been improved if re-planning had been conducted. The results of these retrospective analyses indicate the importance of daily dose monitoring followed by adaptive re-planning when needed. CONCLUSIONS: The tumor registration in proton treatment for HCC was effective to maintain the daily dose to the tumor and the dose constraints of OARs, particularly in the treatment where the maintenance for the dose constraints needs to be considered throughout the treatment. Nevertheless daily proton dose monitoring with daily CT imaging is important for more reliable and safer treatment.

A new target localization method for image-guided radiation therapy of prostate cancer.

In imaged-guided radiation therapy (IGRT), target localization is usually done with rigid-body registration based on anatomy matching. Problems arise when the target volume can only be matched partially due to inter-fractional organ motion and deformation, resulting in deteriorated target coverage and critical structure sparing. A new target localization method is investigated in which the treatment target volume is aligned with the prescription isodose surface. Our study included 15 prostate patients previously treated with intensity-modulated radiation therapy (IMRT). Patient setup and target localization were performed using a CT-on-rails system before and after the IMRT treatment. IMRT plans were generated on the original simulation CTs (15) and the same MUs and leaf sequences were used to compute the dose distributions on post-treatment CTs (98) with the isocenter adjustments based on either anatomical structure matching or prescription isodose surface alignment. When patients were aligned with the traditional anatomy matching method, the dose to 95% of the CTV, D95, received 74.0 - 77.6 Gy and the minimum CTV dose, Dmin, was 61.9 - 71.6 Gy, respectively, in the cumulative dose distributions. The rectal dose-volume constraints were violated in 35.7% of the treatment fractions. When patients were aligned using the new localization method, the dose to 95% of the CTV, D95, received 74.0 - 78.2 Gy and the minimum CTV dose, Dmin, was 68.4 - 71.6 Gy, respectively, in the cumulative dose distributions. The rectal dose-volume constraints were violated in 17.3% of the treatment fractions. Traditional IGRT target localization based on anatomy matching is effective for population-based PTV margins but not ideal for those patients with large inter-fractional prostate rotation/deformation due to large rectal and bladder volume variation. The new method using the prescription isodose surface to align the target volume could improve the target coverage and rectal sparing for these patients, which can be implemented clinically to improve target dose delivery accuracy.

An exploratory analysis of MR-guided fractionated stereotactic radiotherapy in patients with brain metastases.

Purpose: To assess the feasibility and potential benefits of online adaptive MR-guided fractionated stereotatic radiotherapy (FSRT) in patients with brain metastases (BMs). Methods and materials: Twenty-eight consecutive patients with BMs were treated with FSRT of 30 Gy in 5 fractions on the 1.5 T MR-Linac. The FSRT fractions employed daily MR scans and the contours were utilized to create each adapted plan. The brain lesions and perilesional edema were delineated on MR images of pre-treatment simulation (Fx0) and all fractions (Fx1, Fx2, Fx3, Fx4 and Fx5) to evaluate the inter-fractional changes. These changes were quantified using absolute/relative volume, Dice similarity coefficient (DSC) and Hausdorff distance (HD) metrics. Planning target volume (PTV) coverage and organ at risk (OAR) constraints were used to compare non-adaptive and adaptive plans. Results: A total of 28 patients with 88 lesions were evaluated, and 23 patients (23/28, 82.1%) had primary lung adenocarcinoma. Significant tumor volume reduction had been found during FSRT compared to Fx0 for all 88 lesions (median -0.75%, -5.33%, -9.32%, -17.96% and -27.73% at Fx1, Fx2, Fx3, Fx4 and Fx5, p < 0.05). There were 47 (47/88, 53.4%) lesions being accompanied by perilesional edema and the inter-fractional changes were significantly different compared to those without perilesional edema (p < 0.001). Patients with multiple lesions (13/28, 46.4%) had more significant inter-fractional tumor changes than those with single lesion (15/28, 53.6%), including tumor volume reduction and anatomical shift (p < 0.001). PTV coverage of non-adaptive plans was below the prescribed coverage in 26/140 fractions (19%), with 12 (9%) failing by more than 10%. All 140 adaptive fractions met prescribed target coverage. The adaptive plans also had lower dose to whole brain than non-adaptive plans (p < 0.001). Conclusions: Significant inter-fractional tumor changes could be found during FSRT in patients with BMs treated on the 1.5 T MR-Linac. Daily MR-guided re-optimization of treatment plans showed dosimetric benefit in patients with perilesional edema or multiple lesions.

Biofidelic image registration for head and neck region utilizing an in-silico articulated skeleton as a transformation model.

Objective.We propose an integration scheme for a biomechanical motion model into a deformable image registration. We demonstrate its accuracy and reproducibility for adaptive radiation therapy in the head and neck region.Approach. The novel registration scheme for the bony structures in the head and neck regions is based on a previously developed articulated kinematic skeleton model. The realized iterative single-bone optimization process directly triggers posture changes of the articulated skeleton, exchanging the transformation model within the deformable image registration process. Accuracy in terms of target registration errors in the bones is evaluated for 18 vector fields of three patients between each planning CT and six fraction CT scans distributed along the treatment course.Main results. The median of target registration error distribution of the landmark pairs is 1.4 ± 0.3 mm. This is sufficient accuracy for adaptive radiation therapy. The registration performs equally well for all three patients and no degradation of the registration accuracy can be observed throughout the treatment.Significance. Deformable image registration, despite its known residual uncertainties, is until now the tool of choice towards online re-planning automation. By introducing a biofidelic motion model into the optimization, we provide a viable way towards an in-build quality assurance.

Correlation of Brain Metastasis Shrinking and Deviation During 10-Fraction Stereotactic Radiosurgery With Late Sequela: Suggesting Dose Ramification Between Tumor Eradication and Symptomatic Radionecrosis.

Stereotactic radiosurgery (SRS) with >5 fraction (fr) has been increasingly adopted for brain metastases (BMs), given the current awareness of limited brain tolerance for ≤5 fr. The target volume/configuration change and/or deviation within the cranium during fractionated SRS can be unpredictable and critical uncertainties affecting treatment accuracy, plus the effect of these events on the long-term outcome remains uncertain. Herein, we describe a case of two challenging BMs treated by 10 fr SRS with a unique dose-gradient optimization strategy, in which the large cystic tumor revealed an intriguing correlation of such inter-fractional change with late radiographic sequela, suggesting a dose threshold for attaining long-term local tumor control and being immune to symptomatic brain necrosis. A 63-year-old man presented with two cystic lesions located in the left parietal lobe (19.9 cm3) and pons (1.1 cm3) one month after surgery for esophageal squamous cell carcinoma. The principles for 10 fr SRS were as follows: (1) very inhomogeneous gross tumor volume (GTV) dose covered by 53 Gy, biologically effective dose with an alpha/beta ratio of 10 (BED10) of ≥80 Gy; (2) moderate dose spillage margin outside the GTV boundary: 2-2.5 mm outside the GTV margin was covered by 37 Gy, BED10 of ≈50 Gy; (3) concentrically-laminated, steep dose increase inside the GTV boundary: 2 mm inside the GTV margin was covered by ≥62 Gy, BED10 of ≥100 Gy. At the completion of SRS, the parietal lesion showed significant shrinking and dorsomedial shifting with slight evisceration of the GTV, followed by marked regression of the parietal lesion within four months. At 13.5 months, a cystic change was noted at the dorsal part of the remnant. At 16.7 months, ventral enhancement gradually expanded without enlargement of the dorsal cystic component. On the T2-weighted images, the dorsal low-intensity remnant and ventral iso-intensity blurry-demarcated component were contrasting. Pathological examinations during and after lesionectomy at 17.4 months revealed necrosis only. At 30.5 months, the patient had a left visual field defect without recurrence. In contrast, the pons lesion showed no notable change during 10 fr SRS and nearly complete remission over six months with its sustainment without radiation injury at 30.5 months. Taken together, 10 fr SRS with a sufficient BED10 can provide superior tumor response and safety for BM that is not amenable to ≤5 fr SRS. Although a very inhomogeneous GTV dose can contribute to early and adequate tumor shrinkage and subsequent local tumor eradication, significant tumor shrinkage during fractionated SRS (fSRS) inevitably results in unnecessary higher dose exposure to the surrounding brain, which could lead to late radiation injury requiring intervention. The optimum dose should be determined through further investigation, in consideration of the dynamic and unpredictable nature of the actual absorbed doses to both the tumor and the surrounding brain.

Clinical validation of a semi-automated segmentation algorithm for target volume definition on planning CT and CBCT in stereotactic body radiotherapy (SBRT) for peripheral lung lesions.

INTRODUCTION: Stereotactic body radiotherapy (SBRT) is an ablative method for lung malignancies. Here, the definition of the gross target volume (GTV) is subject to interobserver variation. In this study, we aimed to evaluate the interobserver variability during SBRT and its dosimetric impact, as well as to introduce a semi-automated delineation tool for both planning computer tomography (P-CT) and cone beam CT (CBCT) to help to standardise GTV delineation and adaptive volume-change registration. METHODS: The interobserver variation of GTV manual contours from five physicians was analysed in 15 patients after lung SBRT on free breathing (FB) P-CT (n = 15) and CBCT (n = 90) before and after each fraction. The dosimetric impact from interobserver variations of GTV based on the original treatment plan was analysed. Next, the accuracy of an in-house easy-to-use semi-automated-segmentation algorithm for pulmonary lesions was compared with gold standard contours in FB P-CT and CBCT, as well as 4D P-CT of additional 10 patients. RESULTS: The interobserver variability in manual contours resulted in violations of dose coverage of the planning target volume (PTV), which, in turn, resulted in compromised tumour control probability in contours from four physicians. The validation of the semi-automated delineation algorithm using thorax phantom led to a highly reliable accuracy in defining GTVs. Comparing the unsupervised auto-contours with the gold standard delineation revealed high equal high concordance for FB P-CT, 4D P-CT and CBCT, with a DSC of 0.83, 0.76 and 0.8, respectively. The supervised use of the semi-automated delineation tool improved its accuracy, with DSCs of 0.86, 0.86 and 0.8 for FB P-CT, 4D P-CT and CBCT, respectively. The use of the algorithm was associated with a significantly shorter working time. The semi-automated delineation tool can accurately register volume changes in CBCTs. CONCLUSION: The segmentation algorithm provides a reliable, standardised and time-saving alternative for manual delineation in lung SBRT in P-CT and CBCT.

Optimal planning target margin for prostate radiotherapy based on interfractional and intrafractional variability assessment during 1.5T MRI-guided radiotherapy.

Introduction: We analyzed daily pre-treatment- (PRE) and real-time motion monitoring- (MM) MRI scans of patients receiving definitive prostate radiotherapy (RT) with 1.5 T MRI guidance to assess interfractional and intrafractional variability of the prostate and suggest optimal planning target volume (PTV) margin. Materials and methods: Rigid registration between PRE-MRI and planning CT images based on the pelvic bone and prostate anatomy were performed. Interfractional setup margin (SM) and interobserver variability (IO) were assessed by comparing the centroid values of prostate contours delineated on PRE-MRIs. MM-MRIs were used for internal margin (IM) assessment, and PTV margin was calculated using the van Herk formula. Results: We delineated 400 prostate contours on PRE-MRI images. SM was 0.57 ± 0.42, 2.45 ± 1.98, and 2.28 ± 2.08 mm in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively, after bone localization and 0.76 ± 0.57, 1.89 ± 1.60, and 2.02 ± 1.79 mm in the LR, AP, and SI directions, respectively, after prostate localization. IO was 1.06 ± 0.58, 2.32 ± 1.08, and 3.30 ± 1.85 mm in the LR, AP, and SI directions, respectively, after bone localization and 1.11 ± 0.55, 2.13 ± 1.07, and 3.53 ± 1.65 mm in the LR, AP, and SI directions, respectively, after prostate localization. Average IM was 2.12 ± 0.86, 2.24 ± 1.07, and 2.84 ± 0.88 mm in the LR, AP, and SI directions, respectively. Calculated PTV margin was 2.21, 5.16, and 5.40 mm in the LR, AP, and SI directions, respectively. Conclusions: Movements in the SI direction were the largest source of variability in definitive prostate RT, and interobserver variability was a non-negligible source of margin. The optimal PTV margin should also consider the internal margin.

Detailed dosimetric evaluation of inter-fraction and respiratory motion in lung stereotactic body radiation therapy based on daily 4D cone beam CT images.

Objective. Periodic respiratory motion and inter-fraction variations are sources of geometric uncertainty in stereotactic body radiation therapy (SBRT) of pulmonary lesions. This study extensively evaluates and validates the separate and combined dosimetric effect of both factors using 4D-CT and daily 4D-cone beam CT (CBCT) dose accumulation scenarios.Approach. A first cohort of twenty early stage or metastatic disease lung cancer patients were retrospectively selected to evaluate each scenario. The planned-dose (3DRef) was optimized on a 3D mid-position CT. To estimate the dosimetric impact of respiratory motion (4DRef), inter-fractional variations (3DAcc) and the combined effect of both factors (4DAcc), three dose accumulation scenarios based on 4D-CT, daily mid-cone beam CT (CBCT) position and 4D-CBCT were implemented via CT-CT/CT-CBCT deformable image registration (DIR) techniques. Each scenario was compared to 3DRef.A separate cohort of ten lung SBRT patients was selected to validate DIR techniques. The distance discordance metric (DDM) was implemented per voxel and per patient for tumor and organs at risk (OARs), and the dosimetric impact for CT-CBCT DIR geometric errors was calculated.Main results.Median and interquartile range (IQR) of the dose difference per voxel were 0.05/2.69 Gy and -0.12/2.68 Gy for3DAcc-3DRefand4DAcc-3DRef.For4DRef-3DRefthe IQR was considerably smaller -0.15/0.78 Gy. These findings were confirmed by dose volume histogram parameters calculated in tumor and OARs. For CT-CT/CT-CBCT DIR validation, DDM (95th percentile) was highest for heart (6.26 mm)/spinal cord (8.00 mm), and below 3 mm for tumor and the rest of OARs. The dosimetric impact of CT-CBCT DIR errors was below 2 Gy for tumor and OARs.Significance. The dosimetric impact of inter-fraction variations were shown to dominate those of periodic respiration in SBRT for pulmonary lesions. Therefore, treatment evaluation and dose-effect studies would benefit more from dose accumulation focusing on day-to-day changes then those that focus on respiratory motion.

In-vivo range verification analysis with in-beam PET data for patients treated with proton therapy at CNAO.

Morphological changes that may arise through a treatment course are probably one of the most significant sources of range uncertainty in proton therapy. Non-invasive in-vivo treatment monitoring is useful to increase treatment quality. The INSIDE in-beam Positron Emission Tomography (PET) scanner performs in-vivo range monitoring in proton and carbon therapy treatments at the National Center of Oncological Hadrontherapy (CNAO). It is currently in a clinical trial (ID: NCT03662373) and has acquired in-beam PET data during the treatment of various patients. In this work we analyze the in-beam PET (IB-PET) data of eight patients treated with proton therapy at CNAO. The goal of the analysis is twofold. First, we assess the level of experimental fluctuations in inter-fractional range differences (sensitivity) of the INSIDE PET system by studying patients without morphological changes. Second, we use the obtained results to see whether we can observe anomalously large range variations in patients where morphological changes have occurred. The sensitivity of the INSIDE IB-PET scanner was quantified as the standard deviation of the range difference distributions observed for six patients that did not show morphological changes. Inter-fractional range variations with respect to a reference distribution were estimated using the Most-Likely-Shift (MLS) method. To establish the efficacy of this method, we made a comparison with the Beam's Eye View (BEV) method. For patients showing no morphological changes in the control CT the average range variation standard deviation was found to be 2.5 mm with the MLS method and 2.3 mm with the BEV method. On the other hand, for patients where some small anatomical changes occurred, we found larger standard deviation values. In these patients we evaluated where anomalous range differences were found and compared them with the CT. We found that the identified regions were mostly in agreement with the morphological changes seen in the CT scan.

Evaluation of the dosimetric influence of interfractional 6D setup error in hypofractionated prostate cancer treated with IMRT and VMAT using daily kV-CBCT.

INTRODUCTION: Prostate cancer is one of the most common malignant tumors in men and is usually treated with advanced intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). Significant uncorrected interfractional 6-Dimensional setup errors could impact the delivered dose. The aim of this study was to assess the dosimetric impact of 6D interfractional setup errors in hypofractionated prostate cancer using daily kilovoltage cone-beam computed tomography (kV-CBCT). METHODS: This retrospective study comprised twenty prostate cancer patients treated with hypofractionated IMRT (8) and VMAT (12) with daily kV-CBCT image guidance. Interfraction 6D setup errors along lateral, longitudinal, vertical, pitch, roll, and yaw axes were evaluated for 400 CBCTs. For targets and organs at risk (OARs), the dosimetric impact of rotational error (RError), translational error (TError), and translational plus rotational error (T+RError) were evaluated on kV-CBCT images. RESULTS: The single fraction maximum TError ranged from 12-20 mm, and the RError ranged from 2.80-3.00. The maximum mean absolute dose variation ΔD in D98% (dose to 98% volume) of CTV-55 and PTV-55 was -0.66±0.82 and -5.94±3.8 Gy, respectively, in the T+RError. The maximum ΔD (%) for D98% and D0.035cc in CTV-55 was -4.29% and 2.49%, respectively, while in PTV-55 it was -24.9% and 2.36%. The mean dose reduction for D98% in CTV-55 and D98% and D95% in PTV-55 was statistically significant (p<0.05) for TError and T+RError. The mean dose variation for Dmean and D50% in the rectum was statistically significant (p<0.05) for TError and T+RError. CONCLUSION: The uncorrected interfractional 6D setup error results in significant target underdosing and OAR overdosing in prostate cancer. This emphasizes the need to correct interfractional 6D setup errors daily in IMRT and VMAT.

Inter-fractional entrance dose monitoring as quality assurance using Gafchromic EBT3 film.

Introduction: This study describes a simple method of inter-fractional photon beam monitoring to measure the entrance dose of radiation treatment using Gafchromic EBT3 film. Materials and Methods: The film was placed at the center of a 1-cm thick phantom shaped like a block tray and fixed on the accessory tray of the gantry. The entrance dose was measured following the placement of the film in the accessory tray. The dose distribution calculated with the treatment planning system was compared with the dose distribution on the irradiated EBT3 films. The effectiveness of this methodology, as determined by gamma passing rates, was evaluated for the 22 fields of eight three-dimensional conformal radiotherapy (3D-CRT) plans and the 41 fields of nine intensity-modulated radiotherapy (RT) plans. The plans for three-dimensional conformal RT included treatments of the rectum, liver, breast, and head and neck, whereas the plans for intensity-modulated RT included treatments of the liver, brain, and lung. Results: The gamma passing rates for 3D-CRT ranged from 96.4% to 99.5%, with the mean gamma passing rate for 22 fields being 98.0%. The gamma passing rate for intensity-modulated RT ranged from 96.1% to 98.9%, with the mean gamma passing rate for 41 fields being 97.7%. All gamma indices were over the 95% tolerance level. Conclusions: The methodology described in this study, based on Gafchromic EBT3 film, can be utilized for inter-fractional entrance dose monitoring as quality assurance during RT. Clinical application of this method to patients can verify the accuracy of beam delivery in the treatment room.