Intrafractional Variations Research Articles

PO-1722 Investigation of principal modes of intra-fraction anatomical shape variations in the prostate

PO-1722 Investigation of principal modes of intra-fraction anatomical shape variations in the prostate

PO-1719 Intra-fractional variation during daily online adaptive radiotherapy of bladder cancer

PO-1719 Intra-fractional variation during daily online adaptive radiotherapy of bladder cancer

A Review of Proton Therapy - Current Status and Future Directions.

The original rationale for proton therapy was the highly conformal depth-dose distributions that protons are able to produce, compared to photons, which allow greater sparing of normal tissues and escalation of tumor doses, thus potentially improving outcomes. Additionally, recent research, which is still ongoing, has revealed previously unrecognized advantages of proton therapy. For instance, the higher relative biological effectiveness (RBE) near the end of the proton range can be exploited to increase the difference in biologically effective dose in tumors vs. normal tissues. Moreover, the smaller "dose bath", i.e., the compact nature of proton dose distributions has been found to reduce exposure of circulating lymphocytes and the immune organs at risk. There is emerging evidence that the resulting sparing of the immune system has the potential to improve outcomes. Protons, accelerated to therapeutic energies ranging from 70 to 250 MeV, are transported to the treatment room where they enter the treatment head mounted on a rotating gantry. The initially narrow beams of protons are spread laterally and longitudinally and shaped appropriately to deliver treatments. Spreading and shaping can be achieved by electro-mechanically for "passively-scattered proton therapy' (PSPT); or using magnetic scanning of thin "beamlets" of protons of a sequence of initial energies. The latter technique is used to treat patients with optimized intensity modulated proton therapy (IMPT), the most powerful proton therapy modality, which is rapidly supplanting PSPT. Treatment planning and plan evaluation for proton therapy require different techniques compared to photon therapy due, in part, to the greater vulnerability of protons to uncertainties, especially those introduced by inter- and intra-fractional variations in anatomy. In addition to anatomic variations, other sources of uncertainty in the treatments delivered include the approximations and assumptions of models used for computing dose distributions and the current practice of proton therapy of assuming the RBE to have a constant value of 1.1. In reality, the RBE is variable and a complex function of proton energy, dose per fraction, tissue and cell type, end point, etc. Despite the high theoretical potential of proton therapy, the clinical evidence supporting its broad use has so far been mixed. The uncertainties and approximations mentioned above, and the technological limitations of proton therapy may have diminished its true clinical potential. It is generally acknowledged that proton therapy is safe, effective and recommended for many types of pediatric cancers, ocular melanomas, chordomas and chondrosarcomas. Promising results have been and continue to be reported for many other types of cancers as well; however, they are based on small studies. At the same time, there have been reports of unforeseen toxicities. Furthermore, because of the high cost of establishing and operating proton therapy centers, questions are often raised about the value of proton therapy. The general consensus is that there is a need for continued improvement in the state of the art of proton therapy. There is also a need to conduct randomized trials and/or collect outcomes data in multi-institutional registries to generate high level evidence of the advantages of protons. Fortuitously, such efforts are taking currently place. Ongoing research is aimed at better understanding the biological and immunomodulatory effects of proton therapy and the consequences of the physical uncertainties on proton therapy and reducing them through image-guidance and adaptive radiotherapy. Since residual uncertainties will remain despite our best efforts, in order to increase the resilience of dose distributions in the face of uncertainties and improve our confidence in dose distributions seen on treatment plans, robust optimization techniques are being developed and implemented and continue to be perfected. Such research and continuing technological advancements in planning and delivery methods are likely to help demonstrate the superiority of protons.

Comparison of intrafractional motion with two frameless immobilization systems in surface-guided intracranial stereotactic radiosurgery.

Purpose/objectivesThe aim of this study is to compare intrafractional motion using two commercial non‐invasive immobilization systems for linac‐based intracranial stereotactic radiosurgery (SRS) under guidance with a surface‐guided radiotherapy (SGRT) system.Materials/methodsTwenty‐one patients who received intracranial SRS were retrospectively selected. Ten patients were immobilized with a vacuum fixation biteplate system, while 11 patients were immobilized with an open‐face mask system. A setup margin of 1 mm was used in treatment planning. Real‐time surface motion data in 37 treatment fractions using the vacuum fixation system and 44 fractions using the open‐face mask were recorded by an SGRT system. Variances of intrafractional motion along three translational directions and three rotational directions were compared between the two immobilization techniques with Levene's tests. Intrafractional motion variation over time during treatments was also evaluated.ResultsUsing the vacuum fixation system, the average and standard deviations of the shifts were 0.01 ± 0.18 mm, ‐0.06 ± 0.30 mm, and 0.02 ± 0.26 mm in the anterior–posterior (AP), superior–inferior (SI), and left–right (LR) directions, and ‐0.02 ± 0.19°, ‐0.01 ± 0.13°, and 0.01 ± 0.13° for rotations in yaw, roll, and pitch, respectively; using the open‐face mask system, the average and standard deviations of the shifts were ‐0.06 ± 0.20 mm, ‐0.02 ± 0.35 mm, and 0.01 ± 0.40 mm in the AP, SI, and LR directions, and were 0.05 ± 0.23°, 0.02 ± 0.21°, and 0.00 ± 0.16° for rotations in yaw, roll, and pitch, respectively. There was a significant increase in intrafractional motion variance over time during treatments.ConclusionPatients with the vacuum fixation system had significantly smaller intrafractional motion variation compared to those with the open‐face mask system. Using intrafractional motion techniques such as surface imaging system is recommended to minimize dose deviation due to intrafractional motion. The increase in intrafractional motion over time indicates clinical benefits with shorter treatment time.

Online adaptive radiotherapy of urinary bladder cancer with full re-optimization to the anatomy of the day: Initial experience and dosimetric benefits

Background and purposeOnline adaptive radiotherapy (oART) potentially reduces the dose to organs at risk (OARs) as the planning target volume (PTV) margins are reduced compared to a non-adaptive approach (non-ART). This study evaluates the feasibility and dosimetric impact of cone-beam computed tomography (CBCT)-guided oART of urinary bladder cancer for the first patients treated, using patient-specific margins. Materials and methodsSixteen consecutive patients with muscle-invasive bladder cancer received two or more (median = 23) fractions as oART, and remaining fractions as non-ART. The non-ART fractions were delivered with standard population-based margins, while reduced patient-specific margins based on intra-fractional variations extracted from 2-4 fractions were applied to the primary PTV (PTV-T) during the oART fractions. Target volume and coverage, and dose to OARs were compared between non-ART and oART plans, and the oART procedure time was recorded. ResultsIn total, 297/512 fractions were delivered as oART with full re-optimization to the anatomy of the day. The median (interquartile range, IQR) oART procedure time, measured from the end of CBCT generation to completion of plan review, and quality assurance was 13.9 (11.9;16.6) min. The median (IQR) volume reduction in PTV-T volume was 33.9 (24.2;45.0)%, comparing oART and non-ART plans, resulting in median (IQR) reductions in bowel bag V45Gy of 18.8 (12.7;27.9)% and rectum V50Gy of 70.7 (35.9;94.8)%. By re-optimizing the plan to the daily anatomy, full target coverage was achieved at all oART fractions. ConclusionsoART resulted in large reductions in treatment volumes and doses to OARs, compared to non-ART, while ensuring target coverage. This indicates potential reductions in gastrointestinal toxicity.

Gating has a negligible impact on dose delivered in MRI-guided online adaptive radiotherapy of prostate cancer

Background and purposeMR-guided radiotherapy (MRgRT) allows real-time beam-gating to compensate for intra-fractional target position variations. This study investigates the dosimetric impact of beam-gating and the impact of PTV margin on prostate coverage for prostate cancer patients treated with online-adaptive MRgRT. Materials and methods20 consecutive prostate cancer patients were treated with online-adaptive MRgRT SBRT with 36.25 Gy in 5 fractions (PTV D95% ≥ 95% (N = 5) and PTV D95% ≥ 100% (N = 15)). Sagittal 2D cine MRIs were used for gating on the prostate with a 3 mm expansion as the gating window. We computed motion-compensated dose distributions for (i) all prostate positions during treatment (simulating non-gated treatments) and (ii) for prostate positions within the gating window (gated treatments). To evaluate the impact of PTV margin on prostate coverage, we simulated coverage with smaller margins than clinically applied both for gated and non-gated treatments. Motion-compensated fraction doses were accumulated and dose metrics were compared. ResultsWe found a negligible dosimetric impact of beam-gating on prostate coverage (median of 0.00 Gy for both D95% and Dmean). For 18/20 patients, prostate coverage (D95% ≥ 100%) would have been ensured with a prostate-to-PTV margin of 3 mm, even without gating. The same was true for all but one fraction. ConclusionBeam-gating has negligible dosimetric impact in online-adaptive MRgRT of prostate cancer. Accounting for motion, the clinically used prostate-to-PTV margin could potentially be reduced from 5 mm to 3 mm for 18/20 patients.

Heart-Sparing Capability and Positional Reproducibility of Continuous Positive Airway Pressure in Left-Sided Breast Radiation Therapy

PurposeOur purpose was to investigate the interfraction and intrafraction reproducibility and practical applicability of continuous positive airway pressure (CPAP) for left breast volumetric modulated arc therapy (VMAT). Methods and MaterialsInterfraction reproducibility of the position of the heart was evaluated by measuring the heart-to-target distance on 20 planning computed tomography (CT) and 300 daily cone beam CT of 20 patients with left breast cancer treated with a 15-fraction VMAT. The dosimetric metrics of the whole heart and its substructures were compared between CPAP and free-breathing based VMAT plans. Intrafraction reproducibility was evaluated by measuring the motions of the breast target and diaphragm in 4-dimensional CT of 20 female patients with nonbreast cancer. Lastly, we analyzed the CPAP compliance data of 237 consecutive patients with left-sided breast cancer with and without internal mammary node irradiation (IMNI). ResultsThe heart position was reproducible as evidenced by an absolute average heart-to-target distance error of 2.0 ± 2.0 mm. Compared with free-breathing, CPAP significantly reduced the mean heart dose and the dose to the left ventricle and left anterior descending artery. The average intrafraction position variation of the breast target was 0.5 ± 0.5, 2.5 ± 2.0, and 1.8 ± 1.4 mm in the mediolateral, craniocaudal, and anteroposterior directions, respectively. CPAP was successfully applied in 221 patients (93%), with a mean heart dose of 1.6 ± 0.7 Gy (IMNI: 2.0 Gy and no IMNI: 1.1 Gy). ConclusionsCPAP has adequate heart-sparing capability and sufficient reproducibility in VMAT for left-sided breast cancer treatment, with a high compliance rate. Thus, CPAP is applicable in routine practice for left-sided breast cancer radiation therapy.

Impact on liver position under breath-hold by computed tomography contrast agents in stereotactic body radiotherapy of liver cancer.

BackgroundWe investigated variations in liver position relative to the vertebral bone for liver cancer treated with stereotactic body radiation therapy under expiratory phase breath-hold (BH) for treatment with contrast-enhanced-computed tomography (CECT), non-CECT, and cone-beam computed tomography (CBCT).Materials and methodsSeventeen consecutive patients using a contrast enhancement (CE) agent for the CT simulation session for this retrospective study were selected. The first computed tomography (CT) scan without the use of CE agent in the expiratory phase was used for treatment planning (pCT). The remaining three CT scans without a CE agent under expiratory phase BH were acquired successively without repositioning to evaluate the intra-fraction variation in liver position. Furthermore, a three-phase CT scan (arterial, portal, and late phases) accompanied by a CE agent under expiratory phase BH was acquired for target delineation. CBCT scans without the use of a CE agent under expiratory phase BH were acquired for treatment. Inter-fractional variations (non-CECT or CECT) in liver position were measured using the difference between CBCT and pCT or each 3 phase CECT images, respectively.ResultsThe average ± standard deviations for intrafractional, non-CECT interfractional variations, and CECT interfractional variations were 1.0 ± 1.3, 2.5 ± 2.6, and 6.4 ± 6.4 mm, respectively, in the craniocaudal (CC) direction. Intra- and inter-fractional variations in liver position were relatively small for non-CECT. However, significant inter-fractional liver position variations in CECT were observed in the expiratory phase BH. The position of the liver should be carefully considered when applying CECT images for image-guided radiotherapy.

Brain Linac-Based Radiation Therapy: "Test Drive" of New Immobilization Solution and Surface Guided Radiation Therapy.

Aim: To test inter-fraction reproducibility, intrafraction stability, technician aspects, and patient/physician’s comfort of a dedicated immobilization solution for Brain Linac-based radiation therapy (RT). Methods: A pitch-enabled head positioner with an open-face mask were used and, to evaluate inter- and intrafraction variations, 1–3 Cone-Beam Computed Tomography (CBCT) were performed. Surface Guided Radiation Therapy (SGRT) was used to evaluate intrafraction variations at 3 time points: initial (i), final (f), and monitoring (m) (before, end, and during RT). Data regarding technician mask aspect were collected. Results: Between October 2019 and April 2020, 69 patients with brain disease were treated: 45 received stereotactic RT and 24 conventional RT; 556 treatment sessions and 863 CBCT’s were performed. Inter-fraction CBCT mean values were longitudinally 0.9 mm, laterally 0.8 mm, vertically 1.1 mm, roll 0.58°, pitch 0.59°, yaw 0.67°. Intrafraction CBCT mean values were longitudinally 0.3 mm, laterally 0.3 mm, vertically 0.4 mm, roll 0.22°, pitch 0.33°, yaw 0.24°. SGRT intrafraction mean values were: i_, m_, f_ longitudinally 0.09 mm, 0.45 mm, 0.31 mm; i_, m_, f_ laterally 0.07 mm, 0.36 mm, 0.20 mm; i_, m_, f_ vertically 0.06 mm, 0.31 mm, 0.22 mm; i_, m_, f_ roll 0.025°, 0.208°, 0.118°; i_, m_, f_ pitch 0.036°, 0.307°, 0.194°; i_, m_, f_ yaw 0.039°, 0.274°, 0.189°. Conclusions: This immobilization solution is reproducible and stable. Combining CBCT and SGRT data confirm that 1 mm CTV-PTV margin for Linac-based SRT was adequate. Using open-face mask and SGRT, for conventional RT, radiological imaging could be omitted.

Prostate deformation during hypofractionated radiotherapy: an analysis of implanted fiducial marker displacement

BackgroundTo report prostate deformation during treatment, based on an analysis of fiducial marker positional differences in a large sample.Material and methodsThis study included 144 patients treated with prostate stereotactic body radiation therapy after implantation in each of 4 gold fiducial markers (FMs), which were located and numbered consistently. The center of mass of the FMs was recorded for every pair of X-ray images taken during treatment. The distance between each pair of fiducials in the live X-ray images is calculated and compared with the respective distances as determined in the CT volume. The RBE is the difference between these distances. Mean RBE and intrafraction and interfraction RBE were evaluated. The intrafraction and intefraction RBE variability were defined as the standard deviation, respectively, of all RBE during 1 treatment fraction and of the mean daily RBE over the whole treatment course.ResultsWe analyzed 720 treatment fractions comprising 24,453 orthogonal X-ray image acquisitions. We observed a trend to higher RBE related to FM4 (apex) during treatment. The fiducial marker in the prostate apex could not be used in 16% of observations, in which RBE was > 2.5 mm. The mean RBEavg was 0.93 ± 0.39 mm (range 0.32–1.79 mm) over the 5 fractions. The RBEavg was significantly lower for the first and second fraction compared with the others (P < .001). The interfraction variability of RBEavg was 0.26 ± 0.16 mm (range 0.04–0.74 mm). The mean intrafraction variability of all FMs was 0.45 ± 0.25 mm. The highest Pearson correlation coefficient was observed between FM2 and FM3 (middle left and right prostate) (R = 0.78; P < .001). Every combination with FM4 yielded lower coefficients (range 0.66–0.71; P < .001), indicating different deformation of the prostate apex.ConclusionsIdeally, prostate deformation is generally small, but it is very sensitive to rectal and bladder filling. We observed RBE up to 11.3 mm. The overall correlation between FMs was affected by shifts of individual fiducials, indicating that the prostate is not a “rigid” organ. Systematic change of RBE average between subsequent fractions indicates a systematic change in prostate shape.

Bladder surface dose modeling in prostate cancer radiotherapy: An analysis of motion-induced variations and the cumulative dose across the treatment.

To introduce a novel surface-based dose mapping method to improve quantitative bladder dosimetric assessment in prostate cancer (PC) radiotherapy. Based on the planning and daily pre and postfraction MRIs of 12PC patients, bladder surface models (SMs) were generated on manually delineated contours and regionally aligned via surface-based registration. Subsequently, bladder surface dose models (SDMs) were created using face-wise dose sampling. To determine the bladder intrafractional and interfractional motion and dose variation, we performed a pose analysis between pre and postfraction bladder SMs, as well as surface mapping for fractional SMs. Discrepancies between the received dose, accumulated from daily SDMs, and the planned dose were then assessed on the corresponding SDMs. Complementary to the surface dose mapping, dose surface histogram (DSH)-based comparisons were also performed. The intrafraction pose analysis revealed a significant (p<0.05) bladder expansion, as well as an anterior/superior drift during the treatment. The intrafraction motion substantially altered dose to mid-bladder body, but not the bladder surface areas distal to or contiguous with the target. A similar pattern of dose variations was also detected by interfraction comparisons. With surface registration to the common SM, the cumulative bladder dose significantly differs from the planned dose. The discrepancy is evident in the mid-posterior range that corresponds to a mid- to high-dose region. The received DSH significantly differs from the planned DSH after permutation correction (p=0.0122), while the overall surface-based comparison after multiple comparison correction is nonsignificant (p=0.0800). We developed a novel surface-based intra and interdose mapping framework applied to a unique daily MR dataset for image-guided radiotherapy. The framework identified significant intrafraction bladder positional changes, localized the intra and interfraction variations, and quantified planned versus received dose differences on the bladder surface. The result indicates the importance of adopting the motion-integrated bladder SDM for bladder dose management.

Dosimetric Impact of Intrafraction Motion During Peripheral Lung Cancer Stereotactic Radiotherapy: Is a Second Cone Beam Computed Tomography of Added Value?

In our department, during lung SBRT, all patients (regardless of tumor location) receive an additional intra-fractional CBCT, allowing us to adjust the beam delivery accordingly to the intra-fractional variation (IFV). It is to be expected that each IFV exceeding the planning target volume (PTV) margins could lead to potential discrepancies between planned and delivered plans. A posteriori robust dosimetric evaluation will help us to quantify the actual impact on the target's volumes coverage.Six hundred sixty-four CBCTs from 166 consecutives free-breathing lung SBRT patients were retrospectively analyzed. Treatments were based on the internal target volume (ITV) approach with a 4D-CT at simulation and performed using volumetric modulated arc therapy. An isotropic 0.5 cm margin was used to create the PTV around the ITV. The prescribed dose was 48 Gy in 4 fractions to the PTV (80% isodose line). Patients were divided into two groups: patients for whom the 3D-IFV was below 0.5 cm (low-risk group: 105 patients, 573/664 fractions) and patients with at least one 3D-IFV ≥ 0.5 cm (high-risk group: 61 patients, 91/664 fractions). Plans simulating the dosimetric impact of the IFV were created as follows: the original two arcs were copied into a new plan consisting of 4 times ARC1 and 4 times ARC2. The delivery of ARC1 was always assumed to have occurred with the isocenter coordinates as those in the original plan, whereas the positions of ARC2 were modified for each arc by the measured the 3D displacement for that fraction according to the intra-fraction CBCT.The IFV reduces both the minimal (D99%) and mean (Dmean) dose to both the PTV and the ITV. For the PTV, we obtained: D99(%) = 45.2 vs 48.2 Gy (P < .0001); Dmean = 53 vs 54 Gy (P < .0001) for the reconstructed vs planned dose values, respectively. For the ITV, the changes are less pronounced: D99(%) = 52.2 vs 53.6 Gy (P = .0007); Dmean = 56 vs 56.8 Gy (P = .0144). Maximum dose (Dmax) was not much affected by the IFV for neither the PTV nor the ITV (PTV = 60.3 vs 60 Gy (P = .3686), ITV = 60.2 vs 60 Gy (P = .5125)). The V48(Gy)-ITV coverage did not statistically change between the delivered vs planned dose (P = .1803). For the high-risk IFV group, 4 patients did not achieve 100% coverage of the prescribed dose to the ITV in the reconstructed dose. Two of these were clear outliers (ITV-V48(Gy) = 82.4 and 81.9%). Those were the patients for whom the 3D-IFV > 0.5 cm was observed for 3 and 4 fractions, respectively. Regarding the organs at risk (D99%; Dmean; Dmax): for both the low- and high-risk groups, dose-volume histograms were near-identical (no significant difference).Although IFV results in a significant change between the delivered vs planned dose distributions for the PTV (D99%; V48Gy; Dmean) and on the ITV (D99%; Dmean), the V48Gy-ITV coverage did not statistically change. Based on our data we demonstrated that a single CBCT is sufficient and reliable to manage the IFV during peripheral lung SBRT.

Inter- and Intrafraction Bladder and Rectum Motion in Patients With Cervical Cancer Under MR-Guided Radiotherapy on a 1.5T MR-Linac

Internal bladder and rectum motion occur during radiotherapy for cervix cancer. IMRT planning studies have shown that the quality of radiation delivery is influenced by these anatomical changes. The MR-Linac system allows for daily MR image guidance and real-time imaging throughout the treatment fraction, which is ideal for managing and monitoring both inter-fraction and intrafraction motion, without incurring additional radiation exposure. The study is to evaluate bladder and rectum inter- and intrafraction motion using MRI during the full course of MR-Linac radiotherapy fractions, in preparation of MR-guided online adaptive radiotherapy.Five stage ⅡA - ⅢB cervix cancer patients were treated with 25 × 1.8 Gy fractions on a 1.5T MR-Linac. Each fraction, pre-treatment MRI scans were obtained at the start of every treatment session, and post-treatment MRI scans were obtained at the end of every treatment session. The bladder and rectum were delineated on each MRI by the same radiation oncologist. Inter-fraction and intrafraction variability were evaluated with the Dice similarity coefficient (DSC), the Hausdorff distance (HD), mean distance to agreement (MDA), volume (V) and dose volume parameters.Large inter-fraction motion was found for bladder and rectum due to their filling variation (Bladder: DSC: 0.68 ± 0.17, HD: 30.58 ± 15.32, MDA: 7.77 ± 4.65, V: -23.02% ± 13.13%, Dmean: 2.23% ± 7.10; Rectum: DSC: 0.69 ± 0.04, HD: 22.98 ± 4.02, MDA: 3.45 ± 0.63, V: 13.57% ± 18.09%, Dmean: 0.4% ± 0.7%). Median in-room treatment time pre fraction was 35 min which was much longer than conventional treatment time. The intrafraction motion for bladder was obvious that was explained by the bladder filling variation due to prolonged in-room treatment time per fraction (DSC: 0.88 ± 0.07, HD: 14.66 ± 8.48, MDA: 1.89 ± 1.15, V: 13.06% ± 15.66%, Dmean: -0.89% ± 2.45%). The intrafraction rectum motion was much smaller.Considerable inter-fraction bladder and rectum motion is observed and intrafraction bladder motion which caused by longer treatment time is also obvious in cervical cancer patients on 1.5T MR-Linac. Intrafraction MR-guided online adaptive radiotherapy may potentially further correct this motion.S. Ding: None. H. Liu: None. B. Wang: None. Y. Li: None. B. Liu: None. Y. Ouyang: None. X. Huang: None.

Analysis of Prostate Deformation During Hypofractionated Radiotherapy Based on Implanted Fiducial Markers Displacement

To report the prostate deformation during treatment based on analysis of difference in fiducial markers position in a large sample.This study included 144 patients treated with prostate SBRT (3625 cGy in 5 fractions). Every patient had implanted 4 gold fiducial markers (FMs). The same procedure to locate and mark FMs in the planning system was kept- marker in the base is FM number 1, marker in the apex is FM number 4. Treatment algorithm records the center of mass of implanted FMs for every pair of X-ray images taken during treatment and calculates the average rigid body error (RBEavg) in mm and rigid body error of all separate implanted FMs (RBEf 1-4). The RBE is defined as the distance of a fiducial during treatment from its CT position (visible on DRRs). Mean RBE, intrafraction and interfraction RBE were evaluated. The intrafraction RBE variability was defined as the standard deviation of all RBE during 1 treatment fraction. Interfraction RBE variability was defined as the standard deviation of the mean daily RBE over the whole treatment course. Regression and correlation analysis were used to evaluate correlation between FMs. Repeated measure ANOVA evaluated the change of RBE between treatment fractions.A total of 720 treatment fractions with 24453 X-ray image acquisitions were analyzed. We observed trend for higher RBE related to marker 4 (prostate base) during treatment. From 144 patients, only 1 case (0,7%) dealt with the higher RBE of FM 4 during the 1st fraction. During the 2nd fraction, FM 4 had to be disabled in 10 patients (7%), subsequently in 15 (10%), 16 (11%) and 21 (15%) patients for 3rd, 4th and 5th fraction. The mean RBEavg was 0,93 ± 0,39mm (range 0,1-11,30 mm) over the 5 fractions. The RBEavg was significantly lower for the 1st and 2nd fraction compared to others (P < 0.001). The interfraction variability of RBEavg was 0,26 ± 0,16 mm (Range 0,04 - 0,74 mm). The mean intrafraction variability of all FMs was 0,45 ± 0,25 mm. The highest Pearson correlation coefficient was observed between FM 2 and 3 implanted in the middle left and right portion of the prostate (R = 0,78; P < 0.001). Lower coefficients were observed in every combination with FM4 (range 0,66- 0,71; P < 0,001) what points to different deformation of the prostate apex.In ideal conditions prostate deformation is generally small but very sensitive to rectum and bladder filling. We observed RBE up to 11,3 mm. The overall correlation between FMs was affected by significant shifts of individual fiducials indicating that prostate is not "rigid" organ. Fiducial marker in the prostate apex was not possible to use in 28% of observations for RBE > 2.5mm. The average RBE of all FMs was significantly lower in the 1st fraction indicating prostate shrinkage during radiotherapy.L. Knybel: None. K. Resova: None. Z.Z. Cermakova: None. T. Blazek: None. T. Parackova: None. J. Cvek: None.

Robust Angle Selection in Particle Therapy.

The popularity of particle radiotherapy has grown exponentially over recent years owing to the marked advantage of the depth–dose curve and its unique biological property. However, particle therapy is sensitive to changes in anatomical structure, and the dose distribution may deteriorate. In particle therapy, robust beam angle selection plays a crucial role in mitigating inter- and intrafractional variation, including daily patient setup uncertainties and tumor motion. With the development of a rotating gantry, angle optimization has gained increasing attention. Currently, several studies use the variation in the water equivalent thickness to quantify anatomical changes during treatment. This method seems helpful in determining better beam angles and improving the robustness of planning. Therefore, this review will discuss and summarize the robust beam angles at different tumor sites in particle radiotherapy.

Intra-fractional dosimetric analysis of image-guided intracavitary brachytherapy of cervical cancer

BackgroundTo assess the intra-fractional dosimetric variations of image-guided brachytherapy of cervical cancer.MethodsA total of 38 fractions (9 patients) undergoing brachytherapy for cervical cancer underwent a CT scanning for treatment planning (planning CT) and a Cone-beam CT (CBCT) scanning immediately prior to delivery (pre-delivery CBCT). The variations of volumes as well as the dosimetric impact from treatment planning to delivery (intra-application) were evaluated. The dose volume histogram parameters including volume, D90 of high-risk clinical target volume (HRCTV) and D2cc of organs at risk (OARs) were recorded.ResultsThe relative differences (mean ± 1SD) of the volume and D90 HRCTV across the two scans were − 2.0 ± 3.3% and − 1.2 ± 4.5%, respectively. The variations of D2cc for bladder, rectum, sigmoid and small intestine are − 0.6 ± 17.1%, 9.3 ± 14.6%, 7.2% ± 20.5% and 1.5 ± 12.6%, respectively. Most of them are statistically nonsignificant except the D2cc for rectum, which showed a significant increase (P = 0.001). Using 5% and 10% uncertainty of physical dose for HRCTV at a 6 Gy × 5 high-dose-rate schedule, the possibility of total equivalent doses in 2 Gy fractions (EQD2) lower than 85 Gy is close to 0% and 3%, respectively. Performing similar simulation at 15% and 20% uncertainty of a 4 Gy physical dose for OARs, the possibility of total EQD2 dose exceeding 75 Gy is about 70%. Less than 1% of the total EQD2 of OARs would exceed 80 Gy.ConclusionsAverage intra-fractional dosimetric variation of HRCTV was small in an interval of less than 1 h, and the possibility of total EQD2 exceeding 85 Gy is higher than 97%. The intra-fractional dosimetric variations of OARs might result in an overdose for OARs in a single fraction or the whole treatment. It is necessary to detect unfavorable anatomical changes by re-imaging and take interventions to minimize applied doses and reduce the risk of complications.

Prediction of target position from multiple fiducial markers by partial least squares regression in real-time tumor-tracking radiation therapy.

The purpose of this work is to show the usefulness of a prediction method of tumor location based on partial least squares regression (PLSR) using multiple fiducial markers. The trajectory data of respiratory motion of four internal fiducial markers inserted in lungs were used for the analysis. The position of one of the four markers was assumed to be the tumor position and was predicted by other three fiducial markers. Regression coefficients for prediction of the position of the tumor-assumed marker from the fiducial markers’ positions is derived by PLSR. The tracking error and the gating error were evaluated assuming two possible variations. First, the variation of the position definition of the tumor and the markers on treatment planning computed tomograhy (CT) images. Second, the intra-fractional anatomical variation which leads the distance change between the tumor and markers during the course of treatment. For comparison, rigid predictions and ordinally multiple linear regression (MLR) predictions were also evaluated. The tracking and gating errors of PLSR prediction were smaller than those of other prediction methods. Ninety-fifth percentile of tracking/gating error in all trials were 3.7/4.1 mm, respectively in PLSR prediction for superior–inferior direction. The results suggested that PLSR prediction was robust to variations, and clinically applicable accuracy could be achievable for targeting tumors.

Quantifying inter- and intra-fraction variations of breast cancer radiotherapy with skin dose measurements

Aim. The aim of the current study was to compare between the deep inspiration breath-hold (DIBH) technique and free-breathing (FB) method in the treatment delivery uncertainty of breast cancer radiotherapy using skin dose measurements. Methods. In a prospective manner, eighty patients were randomly selected for skin dose measurements, and they were assigned to two groups. DIBH (40 patients) and FB (40 patients). The systematic inter-fraction dose variation was quantified using the mean percentage error (MPE) between the average measured total dose per session in three consecutive sessions and the corresponding calculated point dose from the treatment planning system. The random inter-fraction dose variation was quantified using the standard deviation (SD) of the dose delivered by the medial or lateral tangential fields, or the total session dose in the three sessions (SDMT, SDLT, or SDtotal, respectively). While the random intra-fraction dose variation was quantified using the SD of the dose difference between the medial and lateral tangential fields in three consecutive sessions (SDMT-LT). Results. There was no statistically significant difference in MPE between the DIBH and FB groups (p = 0.583). Moreover, the mean SDtotal and SDMT of the DIBH group were significantly lower than that of the FB group (2.75 ± 2.33 cGy versus 4.45 cGy ± 4.33, p = 0.048) and (1.94 ± 1.63 cGy versus 3.76 ± 3.42 cGy, p = 0.007), respectively. However, there was no significant difference in the mean SDLT and SDMT-LT between the two groups (p > 0.05). Conclusion. In addition to the advantage of reducing the cardiopulmonary radiation doses in left breast cancer, the DIBH technique could reduce the treatment delivery uncertainty compared to the FB method due to the significant reduction in the random inter-fraction dose variations.

Fiducial-based image-guided SBRT for pancreatic adenocarcinoma: Does inter-and intra-fraction treatment variation warrant adaptive therapy?

PurposeVariation in target positioning represents a challenge to set-up reproducibility and reliability of dose delivery with stereotactic body radiation therapy (SBRT) for pancreatic adenocarcinoma (PDAC). While on-board imaging for fiducial matching allows for daily shifts to optimize target positioning, the magnitude of the shift as a result of inter- and intra-fraction variation may directly impact target coverage and dose to organs-at-risk. Herein, we characterize the variation patterns for PDAC patients treated at a high-volume institution with SBRT.MethodsWe reviewed 30 consecutive patients who received SBRT using active breathing coordination (ABC). Patients were aligned to bone and then subsequently shifted to fiducials. Inter-fraction and intra-fraction scans were reviewed to quantify the mean and maximum shift along each axis, and the shift magnitude. A linear regression model was conducted to investigate the relationship between the inter- and intra-fraction shifts.ResultsThe mean inter-fraction shift in the LR, AP, and SI axes was 3.1 ± 1.8 mm, 2.9 ± 1.7 mm, and 3.5 ± 2.2 mm, respectively, and the mean vector shift was 6.4 ± 2.3 mm. The mean intra-fraction shift in the LR, AP, and SI directions were 2.0 ± 0.9 mm, 2.0 ± 1.3 mm, and 2.3 ± 1.4 mm, respectively, and the mean vector shift was 4.3 ± 1.8 mm. A linear regression model showed a significant relationship between the inter- and intra-fraction shift in the AP and SI axis and the shift magnitude.ConclusionsClinically significant inter- and intra-fraction variation occurs during treatment of PDAC with SBRT even with a comprehensive motion management strategy that utilizes ABC. Future studies to investigate how these variations could lead to variation in the dose to the target and OAR should be investigated. Strategies to mitigate the dosimetric impact, including real time imaging and adaptive therapy, in select cases should be considered.

Geometric Reproducibility of Fiducial Markers and Efficacy of a Patient-Specific Margin Design Using Deep Inspiration Breath Hold for Stereotactic Body Radiation Therapy for Pancreatic Cancer

PurposeIn patients undergoing stereotactic body radiation therapy (SBRT) for pancreatic adenocarcinoma, the reproducibility of tumor positioning between deep-inspiration breath holds is unclear. We characterized this variation with fiducials at simulation and treatment and investigated whether a patient-specific breath-hold (PSBH) margin would help account for intrafraction variation at treatment. Methods and MaterialsWe analyzed 20 consecutive patients with pancreatic cancer who underwent SBRT with deep-inspiration breath holds. At simulation, 3 additional breath-hold scans were acquired immediately after the contrast-enhanced planning computed tomography (CT) scan and used to quantify the mean and maximum variations in the simulation fiducial position (Sim_Varavg and Sim_Varmax), as well as to design the internal target volume (ITV) incorporating a PSBH margin. ResultsAt treatment, a mean of 5 breath-hold cone beam CT (CBCT) scans were acquired per fraction for each patient to quantify the mean and maximum variations in the treatment fiducial position (Tx_Varavg and Tx_Varmax). Various planning target volume (PTV) margins on the gross tumor volume (GTV) versus ITV were evaluated using CBCT scans, with the goal of >95% of fiducials being covered at treatment. The Sim_Varavg and Sim_Varmax were 0.9 ± 0.5 mm and 1.5 ± 0.8 mm in the left-right (LR) direction, 0.9 ± 0.4 mm and 1.4 ± 0.4 mm in the anteroposterior (AP) direction, and 1.5 ± 0.9 mm and 2.1 ± 1.0 mm in the superoinferior (SI) direction, respectively. The Tx_Varavg and Tx_Varmax were 1.2 ± 0.4 mm and 2.0 ± 0.7 mm in the LR direction, 1.1 ± 0.4 mm and 1.8 ± 0.6 mm in the AP direction, and 1.9 ± 1.0 mm and 3.1 ± 1.4 mm in the SI direction, respectively. The ITV was increased by 21.0% ± 8.6% compared with the GTV alone. The PTV margin necessary to encompass >95% of the fiducial locations was 2 mm versus 4 mm in both LR and AP and 4 mm versus 6 mm in SI for the ITV and the GTV, respectively. ConclusionsThe interbreath-hold variation is not insignificant, especially in the SI direction. Acquiring multiple breath-hold CT scans at simulation can help quantify the reproducibility of the interbreath hold and design a PSBH margin for treatment.