Intra-fractional Changes Research Articles

Impact of Intrafractional Changes of Abdominal Gas Cavities in MR-guided Adaptive Radiation Therapy: Is Real-time Adaptation Necessary?

With the introduction of the MR-Linac, online adaptation becomes reality in the clinic. Real-time adaptation is introduced to account for the anatomic changes during the process of online adaptation and RT delivery. In the abdomen, these changes include motions due to respiration, peristalsis and unpredictable gas filling of the gastrointestinal (GI) organs. While real-time motion tracking, a form of real-time adaptation, is being developed to address the respiratory and/or peristaltic motions, the intrafractional change of the gas cavities and its impact on dose delivery has not been investigated. In this work, we study the change of gas volumes in a time frame similar to the duration of online adaptation and fraction dose delivery and its dosimetric impacts during MRI-guided adaptive RT (MRgART). Time-sequenced abdominal MRI sets (3D T2 and T1, or motion average MRI from 4DMRI) separated by 15-60 minutes (mimicking the duration of MRgART) from 9 abdominal cancer patients were analyzed. For each set, the pancreatic head, duodenum, bowels, and stomach were delineated. Gas volumes were contoured separately and justified with corresponding CT. An IMRT plan with a prescription of 50.4 Gy for 28 fractions to the target (the pancreatic head) was created and calculated under magnetic field on the first MR. The electron density was forced to 0.25 for gas and 1 otherwise. The plan was recalculated on the second MR. The effects on dose volume histogram (DVH) parameters due to gas volume changes for a single fraction are reported. The GI gas cavity volumes can change substantially in the duration of 15-60 min. Gas cavities of the stomach and duodenum were found to vary, on average, by 38 and 3.5 cc, respectively, for the cases studied. Changes in selected DVH parameters resulting from these (intrafractional) gas cavity changes are tabulated for a single fraction. The IMRT plans generated on the pancreatic head showed a medium correlation between the stomach gas volume and the maximum dose to the target (|r| = 0.3) and a strong correlation to the target V(97%) (|r| = 0.7) and to the duodenum (|r| = 0.7) is reported. There was a low to medium correlation (|r| = 0.2 – 0.6) between the duodenum gas volume change and the observed DVH parameters despite the comparably smaller volume change. Intrafractional gas volumes vary rapidly within GI structures causing anatomical changes near the target. Such changes can result in a negative impact on the dose delivery, even with online adaptation. These results demonstrate the need to consider real-time adaptation as a means to address the effects of bowel gas variation during MRgART.Abstract 3754; Table 1Max Target Dose (cGy)Min Target Dose (cGy)Target V(97%) (%)Max Duodenum Dose (cGy)Average Difference1.8324.85.4Max Difference5.2931414Min Difference0.00.20.00.1 Open table in a new tab

Dosimetric comparison of library of plans and online MRI-guided radiotherapy of cervical cancer in the presence of intrafraction anatomical changes

BackgroundOnline magnetic resonance imaging (MRI)-guided radiotherapy of cervical cancer has the potential to further reduce dose to organs at risk (OAR) as compared to a library of plans (LOP) approach. This study presents a dosimetric comparison of an MRI-guided strategy with a LOP strategy taking intrafraction anatomical changes into account.MethodsThe 14 patients included in this study were treated with chemo radiation at our institute and received weekly MRIs after informed consent. The MRI-guided strategy consisted of treatment plans created on the weekly sagittal MRI with 3 mm and 5 mm planning target volume (PTV) margin for clinical target volume (CTV) cervix-uterus (MRI_3mm and MRI_5mm). The plans for the LOP strategy were based on interpolations of CTV cervix-uterus on pretreatment full and empty bladder scans. Dose volume histogram (DVH) parameters were compared for targets and OARs as delineated on the weekly transversal MRI, which was acquired on average 10 min after the sagittal MRI.ResultsFor the MRI_5mm strategy D98% of the high-risk CTV was at least 95% for all weekly MRIs of all patients, while for the LOP and MRI_3mm strategy this requirement was not satisfied for at least one weekly MRI for 1 and 3 patients, respectively. The average reduction of the volume of the reference dose (95% of the prescribed dose) as compared to the LOP strategy was 464 cm3 for the MRI_3mm strategy, and 422 cm3 for the MRI_5mm strategy. The bowel bag constraint V40Gy < 350 cm3 was violated for 13 patients for the LOP strategy and for 5 patients for both MRI_3mm and MRI_5mm strategy.ConclusionsWith online MRI-guided radiotherapy of cervical cancer considerable sparing of OARs can be achieved. If a new treatment plan can be generated and delivered within 10 min, an online MRI-guided strategy with a 5 mm PTV margin for CTV cervix-uterus is sufficient to account for intrafraction anatomical changes.Trial registrationNL44492.018.13.

Evaluation of spine structure stability at different locations during SBRT.

Modern stereotactic body radiotherapy (SBRT) techniques and systems that use online image guidance offer frameless radiotherapy of spinal tumors and the ability to control intrafraction motion during treatment. These systems allow precise alignment of the patient during the entire treatment session and react immediately to random changes in this alignment. Online tracking data provide information about intrafractional changes, and this information can be useful for designing treatment strategies even if online tracking is not being used. The present study evaluated spine motion during SBRT treatment to assess the risk of verifying patient alignment only prior to starting treatment. This study included 123 patients treated with spine SBRT. We analyzed different locations within the spine using system log files generated during treatment, which contain information about differences in the pretreatment reference spine positions by CT versus positions during SBRT treatment. The mean spine motion and intra/interfraction motion was evaluated. We defined and assessed the spine stability and spine significant shifts (SSHs) during treatment. We analyzed 462 fractions. For the cervical (C) spine, the greatest shifts were in the anterior-posterior (AP) direction (2.48 mm) and in pitch rotation (1.75 deg). The thoracic (Th) spine showed the biggest shift in the AP direction (3.68 mm) and in roll rotation (1.66 deg). For the lumbar-sacral (LS) spine, the biggest shift was found for left-right (LR) translation (3.81 mm) and roll rotation (3.67 deg). No C spine case exceeded 1 mm/1 deg for interfraction variability, but 7 of 54 Th spine cases exceeded 1 mm interfraction variability for translations (maximum value, 2.5 mm in the AP direction). The interfraction variability for translations exceeded 1 mm in 2 of 24 LS spine cases (maximum value, 1.7 mm in the LR direction). Only 13% of cases had no SSHs. The mean times to SSH were 6.5±3.9 min, 8.1±5.9 min, and 8.8±7.1 min for the C, Th, and LS spine, respectively, and the mean recorded SSH values were 1.6±0.66, 1.43±0.33, and 1.46±0.47 mm/deg, respectively. Positional tracking during spine SBRT treatments revealed low mean translational and rotational shifts. Patient immobilization did not improve spine shifts compared with our results for the Th and LS spine without immobilization. For the most precise spine SBRT, we recommend checking the patient's position during treatment.

Comparison between bone matching and marker matching for evaluation of intra- and inter-fractional changes in accumulated dose of carbon ion radiotherapy for hepatocellular carcinoma

Background and purposeTo determine whether bone matching (BM) or marker matching (MM) is the better positioning technique for carbon ion radiotherapy (CIRT) of primary hepatocellular carcinoma (HCC), we prospectively evaluated accumulated dose distributions with respect to intra- and inter-fractional anatomical changes. Materials and methodsThe accumulated doses in ten patients with HCC were evaluated, with the doses being calculated with respect to inter-fractional changes (InterDose) on treatment-room CT images on day 1 or day 2 of therapy (RefCT). This was accomplished by warping 3-day CT dose distributions to the RefCT through deformable registration. The accumulated doses were also calculated with respect to intra-fractional change (IntraDose) calculated by warping dose distributions for three 4DCT phases to the RefCT. Each dose was evaluated using dose–volume parameters for the clinical target volume (CTV) percentages receiving greater than 95% of the prescription dose (V95). ResultsThe InterDose CTV V95 values (mean [range]) were BM: 98.74% (95.62–100%), MM: 99.79% (98.55–100%), and the IntraDose values were BM: 99.46% (98.10–100%), MM: 99.74% (98.91–100%). Although all cases were acceptable with either matching method, MM provided better values than BM. ConclusionMM is a better positioning technique than BM for ensuring the target dose during and between fractions of CIRT. However, further analysis is required as our study included only a low number of cases.

Real-time adaptive planning method for radiotherapy treatment delivery for prostate cancer patients, based on a library of plans accounting for possible anatomy configuration changes.

Background and purposeIn prostate cancer treatment with external beam radiation therapy (EBRT), prostate motion and internal changes in tissue distribution can lead to a decrease in plan quality. In most currently used planning methods, the uncertainties due to prostate motion are compensated by irradiating a larger treatment volume. However, this could cause underdosage of the treatment volume and overdosage of the organs at risk (OARs). To reduce this problem, in this proof of principle study we developed and evaluated a novel adaptive planning method. The strategy proposed corrects the dose delivered by each beam according to the actual position of the target in order to produce a final dose distribution dosimetrically as similar as possible to the prescribed one.Material and methodsOur adaptive planning method was tested on a phantom case and on a clinical case. For the first, a pilot study was performed on an in-silico pelvic phantom. A “library” of intensity modulated RT (IMRT) plans corresponding to possible positions of the prostate during a treatment fraction was generated at planning stage. Then a 3D random walk model was used to simulate possible displacements of the prostate during the treatment fraction. At treatment stage, at the end of each beam, based on the current position of the target, the beam from the library of plans, which could reproduce the best approximation of the prescribed dose distribution, was selected and delivered. In the clinical case, the same approach was used on two prostate cancer patients: for the first a tissue deformation was simulated in-silico and for the second a cone beam CT (CBCT) taken during the treatment was used to simulate an intra-fraction change. Then, dosimetric comparisons with the standard treatment plan and, for the second patient, also with an isocenter shift correction, were performed.ResultsFor the phantom case, the plan generated using the adaptive planning method was able to meet all the dosimetric requirements and to correct for a misdosage of 13% of the dose prescription on the prostate. For the first clinical case, the standard planning method caused underdosage of the seminal vesicles, respectively by 5% and 4% of the prescribed dose, when the position changes for the target were correctly taken into account. The proposed adaptive planning method corrected any possible missed target coverage, reducing at the same time the dose on the OARs. For the second clinical case, both with the standard planning strategy and with the isocenter shift correction target coverage was significantly worsened (in particular uniformity) and some organs exceeded some toxicity objectives. While with our approach, the most uniform coverage for the target was produced and systematically the lowest toxicity values for the organs at risk were achieved.ConclusionsIn our proof of principle study, the adaptive planning method performed better than the standard planning and the isocenter shift methods for prostate EBRT. It improved the coverage of the treatment volumes and lowered the dose to the OARs. This planning method is particularly promising for hypofractionated IMRT treatments in which a higher precision and control on dose deposition are needed. Further studies will be performed to test more extensively the proposed adaptive planning method and to evaluate it at a full clinical level.

EP-2056: In silico evaluation of VMAT and IMPT against inter- and intrafraction changes for cervix cancer

EP-2056: In silico evaluation of VMAT and IMPT against inter- and intrafraction changes for cervix cancer

Intrafractional Motion of Target Volumes and Organs at Risk Due to Bladder Filling: Implications for MR-Only Prostate Radiation Therapy

As magnetic resonance simulation (MR-SIM) emerges as a primary treatment planning modality for prostate cancer, it becomes critical to quantify the uncertainties introduced in an MR-only workflow. Given the long image acquisition times encountered in MRI, we sought to characterize the temporal and spatial intra-fractional changes between the prostate, seminal vesicles (SVs), and other organs at risk in response to bladder filling conditions. Serial T2-weighted MR-SIM data (3-6 timepoints/subject at 1.0T, 1.5T, or 3.0T, 38 evaluable timepoints) were acquired in 10 immobilized subjects using a fixed bladder filling protocol (bladder void, 20 oz water consumed, 10 oz consumed mid-session). Delineations were performed by one physician including prostate, SVs, and organs at risk (bladder, rectum, penile bulb) to yield 370 evaluable contours. Bony rigid registration (3 degrees of freedom) was performed for serial T2 data to isolate local organ effects. To quantify the impact of systematic bladder filling, temporal assessments of the volumes, center of mass, and Dice similarity coefficients (DSCs) were performed. To assess serial target displacements, centroid differences between the prostate and proximal SVs were compared across timepoints. Subjects had an average bladder volume difference of 62 ± 15% between initial and final timepoints. When compared to the initial prostate volume, mean DSCs of the prostate went from 0.81 ± 0.07 at the middle timepoint to 0.75 ± 0.07 at the final. A large reduction in DSC was observed for the proximal SVs (0.44 ± 0.22 at the middle time point vs. 0.32 ± 0.17 for the final). Overall, the median vector displacement of the penile bulb was 2.2 mm. After excluding a subject with an extreme case of rectal gas, the average rectum volume difference from the initial timepoint was 5.9 ± 10.3%. The prostate showed <1 mm lateral displacement and > 3mm in centroid shift in 6/10 cases (4 posteriorly and 2 anteriorly due to changes in rectal status). The SVs shifted posteriorly with bladder filling (7/10 cases were > 3mm). The centroid differences between the prostate and proximal SVs were >2mm in 4/10, 6/10, and 7/10 of subjects in the left-right, anterior-posterior, and superior-inferior directions, respectively, suggesting that they move independently with bladder status. As bladder filling increased, DSC decreased for the prostate, SVs, and OARs. In addition, large, systematic shifts were observed in the prostate and SVs (particularly anterior/posterior), although these were subject dependent due to confounders such as rectal status. This suggests that care must be taken during patient preparation to minimize these effects. Future work will incorporate dosimetric consequences using MR-only treatment planning in response to non-uniform organ displacement.

Dosimetric impact of intrafraction changes in MR-guided high-dose-rate (HDR) brachytherapy for prostate cancer

PurposeTo assess changes in implant and treatment volumes through the course of a prostate high-dose-rate brachytherapy procedure and their impact on plan quality metrics. Methods and MaterialsSixteen MRI-guided high-dose-rate procedures included a post-treatment MR (ptMR) immediately after treatment delivery (135 min between MR scans). Target and organs at risk (OARs) were contoured, and catheters were reconstructed. The delivered treatment plan was applied to the ptMR image set. Volumes and dosimetric parameters in the ptMR were evaluated and compared with the delivered plan using a paired two-tailed t-test with p < 0.05 considered statistically significant. ResultsAn average increase of 8.9% in prostate volume was observed for whole-gland treatments, resulting in reduction in coverage for both prostate and planning target volume, reflected in decreased V100 (mean 3.3% and 4.6%, respectively, p < 0.05), and D90 (mean 7.1% and 7.6%, respectively, of prescription dose, p < 0.05). There was no significant change in doses to OARs. For partial-gland treatments, there was an increase in planning target volume (9.1%), resulting in reduced coverage and D90 (mean 3.6% and 12.4%, respectively, p < 0.05). A decrease in D0.5cc for bladder (3%, p < 0.05) was observed, with no significant changes in dose to other OARs. ConclusionsVolumetric changes were observed during the time between planning MR and ptMR. Nonetheless, treatment plans for both whole- and partial-gland therapies remained clinically acceptable. These results apply to clinical settings in which patients remain in the same position and under anesthesia during the entire treatment process.

Tumor motion changes in stereotactic body radiotherapy for liver tumors: an evaluation based on four-dimensional cone-beam computed tomography and fiducial markers

BackgroundFor stereotactic body radiation therapy (SBRT) of liver tumors, tumor motion induced by respiration must be taken into account in planning and treatment. We evaluated whether liver tumor motion at the planning simulation represents liver tumor motion during SBRT, and estimated inter- and intrafractional tumor motion changes in patients undergoing liver SBRT.MethodsTen patients underwent four-dimensional cone-beam computed tomography (4D-CBCT) image-guided liver SBRT with abdominal compression (AC) and fiducial markers. 4D-CBCT was performed to evaluate liver tumor motion at the planning simulation, pre-, and post-SBRT. The translational distances at the center position of the fiducial markers from all 10 phases on the 4D-CBCT images were measured as the extent of the liver tumor motion in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions. Pearson correlation coefficients were calculated to evaluate the correlation between liver tumor motion of the planning simulation and the mean liver tumor motion of the pre-SBRT. Inter- and intrafractional liver tumor motion changes were measured based on the 4D-CBCT of planning simulation, pre-, and post-SBRT. Significant inter- and intrafractional changes in liver tumor motion were defined as a change of >3 mm.ResultsThe mean (± SD) liver tumor motion of the planning simulation 4D-CBCT was 1.7 ± 0.8 mm, 2.4 ± 2.2 mm, and 5.3 ± 3.3 mm, in the LR, AP, and SI directions, respectively. Those of the pre-SBRT 4D-CBCT were 1.2 ± 0.7 mm, 2.3 ± 2.3 mm, and 4.5 ± 3.8 mm, in the LR, AP, and SI directions, respectively. There was a strong significant correlation between liver tumor motion of the planning simulation and pre-SBRT in the LR (R = 0.7, P < 0.01), AP (R = 0.9, P < 0.01), and SI (R = 0.9, P < 0.01) directions. Significant inter- and intrafractional liver tumor motion changes occurred in 10 and 2% of treatment fractions, respectively.ConclusionsLiver tumor motion at the planning simulation represents liver tumor motion during SBRT. Inter- and intrafractional liver tumor motion changes were small in patients with AC.

Hydrogel rectum-prostate spacers mitigate the uncertainties in proton relative biological effectiveness associated with anterior-oblique beams

Aim: Anterior-oblique (AO) proton beams can form an attractive option for prostate patients receiving external beam radiotherapy (EBRT) as they avoid the femoral heads. For a cohort with hydrogel prostate-rectum spacers, we asked whether it was possible to generate AO proton plans robust to end-of-range elevations in linear energy transfer (LET) and modeled relative biological effectiveness (RBE). Additionally we considered how rectal spacers influenced planned dose distributions for AO and standard bilateral (SB) proton beams versus intensity-modulated radiotherapy (IMRT).Material and methods: We studied three treatment strategies for 10 patients with rectal spacers: (A) AO proton beams, (B) SB proton beams and (C) IMRT. For strategy (A) dose and LET distributions were simulated (using the TOPAS Monte Carlo platform) and the McNamara model was used to calculate proton RBE as a function of LET, dose per fraction, and photon α/β. All calculations were performed on pretreatment scans: inter- and intra-fractional changes in anatomy/set-up were not considered.Results: For 9/10 patients, rectal spacers enabled generation of AO proton plans robust to modeled RBE elevations: rectal dose constraints were fulfilled even when the variable RBE model was applied with a conservative α/β = 2 Gy. Amongst a subset of patients the proton rectal doses for the planning target volume plans were remarkably low: for 2/10 SB plans and 4/10 AO plans, ≤10% of the rectum received ≥20 Gy. AO proton plans delivered integral doses a factor of approximately three lower than IMRT and spared the femoral heads almost entirely.Conclusion: Typically, rectal spacers enabled the generation of anterior beam proton plans that appeared robust to modeled variation in RBE. However, further analysis of day-to-day robustness would be required prior to a clinical implementation of AO proton beams. Such beams offer almost complete femoral head sparing, but their broader value relative to IMRT and SB protons remains unclear.

SU‐G‐JeP4‐06: Evaluation of Interfractional and Intrafractional Tumor Motion in Stereotactic Liver Radiotherapy, Based On Four‐Dimensional Cone‐Beam Computed Tomography Using Fiducial Markers

Purpose:The purpose of this study was to evaluate the interfractional and intrafractional motion of liver tumors in stereotactic body radiation therapy (SBRT), based on four‐dimensional cone‐beam computed tomography using fiducial markers. (4D‐CBCT).Methods:Seven patients with liver tumors were treated by SBRT with abdominal compression (AC) in five fractions with image guidance based on 4D‐CBCT. The 4D‐CBCT studies were performed to determine the individualized internal margin for the planning simulation. The interfractional and intrafractional changes of liver tumor motion for all patients was measured, based on the planning simulation 4D‐CBCT, pre‐SBRT 4D‐CBCT, and post‐SBRT 4D‐CBCT. The interfractional motion change was calculated from the difference in liver tumor amplitude on pre‐SBRT 4D‐CBCT relative to that of the planning simulation 4D‐CBCT for each fraction. The intrafractional motion change was calculated from the difference between the liver tumor amplitudes of the pre‐ and post‐SBRT 4D‐CBCT for each fraction. Significant interfractional and intrafractional changes in liver tumor motion were defined as a change ≥3 mm. Statistical analysis was performed using the Pearson correlation.Results:The values of the mean amplitude of liver tumor, as indicated by planning simulation 4D‐CBCT, were 1.6 ± 0.8 mm, 1.6 ± 0.9 mm, and 4.9 ± 2.2 mm in the left‐right (LR), anterior‐posterior (AP), and superior‐inferior (SI) directions, respectively. Pearson correlation coefficients between the liver tumor amplitudes, based on planning simulation 4D‐CBCT, and pre‐SBRT 4D‐CBCT during fraction treatment in the LR, AP, and SI directions were 0.6, 0.7, and 0.8, respectively. Interfractional and intrafractional motion changes of ≥3 mm occurred in 23% and 3% of treatment fractions, respectively.Conclusion:The interfractional and intrafractional changes of liver tumor motion were small in most patients who received liver SBRT with AC. In addition, planning simulation 4D‐CBCT was useful for representing liver tumor movement in patients undergoing SBRT.This work was supported by JSPS KAKENHI Grant Number 26861004.

SU‐G‐BRA‐16: Target Dose Comparison for Dynamic MLC Tracking and Mid‐ Ventilation Planning in Lung Radiotherapy Subject to Intrafractional Baseline Drifts

Purpose:Lung tumor motion during radiotherapy can be accounted for by expanded treatment margins, for example using a mid‐ventilation planning approach, or by localizing the tumor in real‐time and adapting the treatment beam with multileaf collimator (MLC) tracking. This study evaluates the effect of intrafractional changes in the average tumor position (baseline drifts) on these two treatment techniques.Methods:Lung stereotactic treatment plans (9‐beam IMRT, 54Gy/3 fractions, mean treatment time: 9.63min) were generated for three patients: either for delivery with MLC tracking (isotropic GTV‐to‐PTV margin: 2.6mm) or planned with a mid‐ventilation approach and delivered without online motion compensation (GTV‐to‐PTV margin: 4.4‐6.3mm). Delivery to a breathing patient was simulated using DynaTrack, our in‐house tracking and delivery software. Baseline drifts in cranial and posterior direction were simulated at a rate of 0.5, 1.0 or 1.5mm/min. For dose reconstruction, the corresponding 4DCT phase was selected for each time point of the delivery. Baseline drifts were accounted for by rigidly shifting the CT to ensure correct relative beam‐to‐target positioning. Afterwards, the doses delivered to each 4DCT phase were accumulated deformably on the mid‐ventilation phase using research RayStation v4.6 and dose coverage of the GTV was evaluated.Results:When using the mid‐ventilation planning approach, dose coverage of the tumor deteriorated substantially in the presence of baseline drifts. The reduction in D98% coverage of the GTV in a single fraction ranged from 0.4‐1.2, 0.6‐3.3 and 4.5‐6.2Gy, respectively, for the different drift rates. With MLC tracking the GTV D98% coverage remained unchanged (+/− 0.1Gy) regardless of drift.Conclusion:Intrafractional baseline drifts reduce the tumor dose in treatments based on mid‐ventilation planning. In rare, large target baseline drifts tumor dose coverage may drop below the prescription, potentially affecting clinical outcome in hypofractionated treatment protocols. Dynamic MLC tracking preserves tumor dose coverage even in the presence of extreme baseline drifts.We acknowledge financial and technical support of the MLC tracking research from Elekta AB. Research at ICR is supported by CRUK under Programme C33589/A19727 and NHS funding to the NIHR Biomedical Research Centre at RMH and ICR. MFF is supported by CRUK under Programme C33589/A19908.

SU‐F‐J‐137: Intrafractional Change of the Relationship Between Internal Fiducials and External Breathing Signal in Pancreatic Cancer Stereotactic Body Radiation Therapy

Purpose:The use of respiratory gating for management of breathing motion during stereotactic body radiation therapy (SBRT) relies on a consistent relationship between the breathing signal and the actual position of the internal target. This relationship was investigated in patients treated for pancreatic cancer.Methods:Four patients with pancreatic cancer undergoing SBRT that had implanted fiducials in the tumor were included in this study. Treatment plans were generated based on the exhale phases (30–70%) from the pre‐treatment 4DCT. The margin between the internal target volume (ITV) and the planning target volume was three mm. After patient setup using cone‐beam CT, simultaneous fluoroscopic imaging and breathing motion monitoring were used during at least three breathing cycles to verify the fiducial position and to optimize the gating window. After treatment, fluoroscopic images were acquired for verification purposes and exported for retrospective analyses. Fiducial positions were determined using a template‐matching algorithm. For each dataset, we established a linear relationship between the fiducial position and the anterior‐posterior (AP) breathing signal. The relationships before and after treatment were compared and the dose distribution impact evaluated.Results:Seven pre‐ and post‐treatment fluoroscopic pairs were available for fiducial position analyses in the superior‐inferior (SI) and left‐right (LR) directions, and five in the AP direction. Time between image acquisitions was typically six to eight minutes. An average absolute change of 1.2±0.7 mm (range: 0.1–1.7) of the SI fiducial position relative to the external signal was found. Corresponding numbers for the LR and AP fiducial positions were 0.9±1.0 mm (range: 0.2–3.0) and 0.5±0.4 mm (range: 0.2–1.2), respectively. The dose distribution impact was small in both the ITV and organs‐at‐risk.Conclusion:The relationship change between fiducial position and external breathing signal has been observed to be about 1 mm in four pancreas SBRT patients, leading to small dose distribution impact.Pettersson and Cervino are funded by a Varian Medical Systems grant.

PV-0228: Size and impact of intra-fractional changes in baseline shift during lung SBRT

PV-0228: Size and impact of intra-fractional changes in baseline shift during lung SBRT

Vector analysis of bladder cancer patient setup utilizing a magnetic resonance image-guided radiation therapy (MR-IGRT) system.

412 Background: Inter and intra-fraction anatomy changes in patients undergoing radiation therapy (RT) for bladder cancer (BC) are common but have thus far been studied with implanted fiducial markers, limited quality 2-D orthogonal films and computed tomography (CT). The adverse impact of daily set-up variation could be more significant than appreciated. Our goal was to employ the soft tissue imaging capabilities of an integrated magnetic resonance image-guided RT (MR-IGRT) system to analyze daily positioning. Methods: Fourteen patients with BC were treated on a MR-IGRT system. Patient setup was performed via volumetric MR imaging with a resolution of 0.15 x 0.15 cm. Alignment was performed according to skin marks then shifts assessed by comparing the treatment volume from the planning CT to the daily MR image. 240 pretreatment MR images were analyzed and 3 shifts were recorded for each image. A vector shift was calculated by combining the square root of the combined sum of the shifts squared. Number of times that the vector of combined shifts would have exceeded the planning tumor volume (PTV) was recorded. Results: Daily volumetric MR imaging allowed for accurate alignment and daily monitoring of bladder volume and normal tissue anatomy. Recorded shifts of the treated volume were 0.9±0.5 cm in the right/left direction, 0.7±0.3 cm in the anterior/posterior direction, and 0.7±0.4 cm in the cranio-caudal direction. In 66 (28%) of cases the vector shift was initially greater than the PTV margin. For 2 patients, pre-treatment MR imaging revealed the tumor reduced in size and dose to the bowel would have exceeded constraints, and treatment adaptation was performed to reduce normal tissue toxicity. Using CTCAE criteria, no grade 3 or higher toxicities have been reported. Conclusions: Accurate and reproducible treatment delivery is required to avoid marginal misses to the target volume as well as excess dose to normal tissue. MR-IGRT allows for excellent soft tissue visualization which enables for the avoidance of potential setups errors by allowing daily alignment changes to ensure the target is included in the PTV. It also allows the ability to make treatment changes based on anatomy variations.

Quantification of intra-fraction changes during radiotherapy of cervical cancer assessed with pre- and post-fraction Cone Beam CT scans

Background and purposeWith the introduction of Intensity Modulated Radiotherapy (IMRT) and image-guided plan-of-the-day strategies, the treatment of cervical cancer has become more sensitive to intra-fraction uncertainties. In this study we quantified intra-fraction changes in cervix-uterus shape, bladder and rectum filling, and patient setup using pre- and post-fraction CBCT scans. Materials and methodsA total of 632 CBCT scans were analyzed for 16 patients with large tip-of-uterus displacement (>2.5cm) measured in an empty and full bladder CT scan. In all scans, the bladder, cervix-uterus, and rectum were delineated. For rectum and bladder, intra-fraction volume changes were assessed. Systematic cervix-uterus intra-fraction displacements were obtained by non-rigidly aligning the pre-fraction cervix-uterus to that in the post-fraction CBCT. Intra-fraction patient setup changes were obtained by rigidly aligning pre- and post-CBCTs using the bony anatomy. ResultsThe mean time between pre- and post-fraction CBCT scan was 20.8min. The group-mean intra-fraction displacements averaged over the cervix-uterus were 0.1±1.4/1.8±1.5/−2.8±1.8 (LR/CC/AP) mm. The group-mean 5th and 95th percentile intra-fraction displacements were −2.3,2.1/−0.8,4.9/−5.8,0.5 (LR/CC/AP) mm. There was a significant correlation between bladder inflow rate and cervix-uterus motion (r=0.6 and p<0.01). Intra-fraction changes in patient setup were 1.3/0.4/0.6 and 1.4/1.0/1.1mm (LR/CC/AP), for systematic and random changes, respectively. ConclusionIntra-fraction cervix-uterus motion can be considerable and should be taken into account using appropriate PTV margins.

Intra-fractional bladder motion and margins in adaptive radiotherapy for urinary bladder cancer

ABSTRACTBackground. The bladder is a tumour site well suited for adaptive radiotherapy (ART) due to large inter-fractional changes, but it also displays considerable intra-fractional motion. The aim of this study was to assess target coverage with a clinically applied method for plan selection ART and to estimate population-based and patient-specific intra-fractional margins, also relevant for a future re-optimisation strategy.Material and methods. Nine patients treated in a clinical phase II ART trial of daily plan selection for bladder cancer were included. In the library plans, 5 mm isotropic margins were added to account for intra-fractional changes. Pre-treatment and weekly repeat magnetic resonance imaging (MRI) series were acquired in which a full three-dimensional (3D) volume was scanned every second min for 10 min (a total of 366 scans in 61 series). Initially, the bladder clinical target volume (CTV) was delineated in all scans. The t = 0 min scan was then rigidly registered to the planning computed tomography (CT) and plan selections were simulated using the CTV_0 (at t = 0 min). To assess intra-fractional motion, coverage of the CTV_10 (at t = 10 min) was quantified using the applied PTV. Population-based margins were calculated using the van Herk margin recipe while patient-specific margins were calculated using a linear model.Results. For 49% of the cases, the CTV_10 extended more than 5 mm outside the CTV_0. However, in 58 of the 61 cases (97%) CTV_10 was covered by the selected PTV. Population-based margins of 14 mm Sup/Ant, 9 mm Post and 5 mm Inf/Lat were sufficient to cover the bladder. Using patient-specific margins, the overlap between PTV and bowel-cavity was reduced from 137 cm3 with the plan selection strategy to 24 cm3.Conclusion. In this phase II ART trial, 5 mm isotropic margin for intra-fractional motion was sufficient even though considerable intra-fractional motion was observed. In online re-optimised ART, population-based margin can be applied although patient-specific margins are preferable.

Technical Note: Intrafractional changes in time lag relationship between anterior-posterior external and superior-inferior internal motion signals in abdominal tumor sites.

To investigate constancy, within a treatment session, of the time lag relationship between implanted markers in abdominal tumors and an external motion surrogate. Six gastroesophageal junction and three pancreatic cancer patients (IRB-approved protocol) received two cone-beam CTs (CBCT), one before and one after treatment. Time between scans was less than 30 min. Each patient had at least one implanted fiducial marker near the tumor. In all scans, abdominal displacement (Varian RPM) was recorded as the external motion signal. Purpose-built software tracked fiducials, representing internal signal, in CBCT projection images. Time lag between superior-inferior (SI) internal and anterior-posterior external signals was found by maximizing the correlation coefficient in each breathing cycle and averaging over all cycles. Time-lag-induced discrepancy between internal SI position and that predicted from the external signal (external prediction error) was also calculated. Mean ± standard deviation time lag, over all scans and patients, was 0.10 ± 0.07 s (range 0.01-0.36 s). External signal lagged the internal in 17/18 scans. Change in time lag between pre- and post-treatment CBCT was 0.06 ± 0.07 s (range 0.01-0.22 s), corresponding to 3.1% ± 3.7% (range 0.6%-10.8%) of gate width (range 1.6-3.1 s). In only one patient, change in time lag exceeded 10% of the gate width. External prediction error over all scans of all patients varied from 0.1 ± 0.1 to 1.6 ± 0.4 mm. Time lag between internal motion along SI and external signals is small compared to the treatment gate width of abdominal patients examined in this study. Change in time lag within a treatment session, inferred from pre- to post-treatment measurements is also small, suggesting that a single measurement of time lag at the session start is adequate. These findings require confirmation in a larger number of patients.

Variation in patient position and impact on carbon-ion scanning beam distribution during prostate treatment.

We assessed the impact of changes in patient position on carbon-ion scanning beam distribution during treatment for prostate cancer. 68 patients were selected. Carbon-ion scanning dose was calculated. Two different planning target volumes (PTVs) were defined: PTV1 was the clinical target volume plus a set-up margin for the anterior/lateral sides and posterior side, while PTV2 was the same as PTV1 minus the posterior side. Total prescribed doses of 34.4 Gy [relative biological effectiveness (RBE)] and 17.2 Gy (RBE) were given to PTV1 and PTV2, respectively. To estimate the influence of geometric variations on dose distribution, the dose was recalculated on the rigidly shifted single planning CT based on two dimensional-three dimensional rigid registration of the orthogonal radiographs before and after treatment for the fraction of maximum positional changes. Intrafractional patient positional change values averaged over all patients throughout the treatment course were less than the target registration error = 2.00 mm and angular error = 1.27°. However, these maximum positional errors did not occur in all 12 treatment fractions. Even though large positional changes occurred during irradiation in all treatment fractions, lowest dose encompassing 95% of the target (D95)-PTV1 was >98% of the prescribed dose. Intrafractional patient positional changes occurred during treatment beam irradiation and degraded carbon-ion beam dose distribution. Our evaluation did not consider non-rigid deformations, however, dose distribution was still within clinically acceptable levels. Inter- and intrafractional changes did not affect carbon-ion beam prostate treatment accuracy.

PD-0462: Towards dosimetric tracking with adaptive VMAT?

was acquired at t = 0, 2, 4, 6, 8, and 10 minutes. Treatment and MR scanning was performed on voided bladders. The bladder CTV was delineated in all scans and each CTV was described using spherical coordinates with origin at the centre of volume of the first scan of the first session of each patient. Population-based 2D margin maps were derived by adapting a published margin recipe for bladder (Meijer et al, IJROBP 2003), characterising in the spherical coordinate system the intra-fractional changes (between the scans at t = 0 min to t = 10 min) in terms of systematic and random errors. Secondly, the possibility of deriving patient-specific intra-fractional margins was explored by using only the bladder expansions occurring in the first two series (the pretreatment and the first week series). A linear model was used to fit the radial changes occurring as a function of time. Focusing on the patients and directions where an expansion larger than 5 mm was observed, the patient-specific margin was defined as the upper 96% confidence limit of the linear coefficient multiplied by the relevant intra-fractional time (here assumed ten minutes). Results: The population-based 2D margin map is shown in Fig 1; when excluding the one female patient, the margins at superior and anterior directions were 14 mm, posterior 9 mm and the other directions (inferior, left and right) 5 mm. Intrafractional margins specific for each patient could be derived from the linear model fit (ranging up to 12 mm; R2 in the range: 0.33-0.68).