Interfractional Anatomic Changes Research Articles

Treatment planning comparison in the PROTECT-trial randomising proton versus photon beam therapy in oesophageal cancer: Results from eight European centres

PurposeTo compare dose distributions and robustness in treatment plans from eight European centres in preparation for the European randomized phase-III PROTECT-trial investigating the effect of proton therapy (PT) versus photon therapy (XT) for oesophageal cancer. Materials and methodsAll centres optimized one PT and one XT nominal plan using delineated 4DCT scans for four patients receiving 50.4 Gy (RBE) in 28 fractions. Target volume receiving 95% of prescribed dose (V95%iCTVtotal) should be >99%. Robustness towards setup, range, and respiration was evaluated. The plans were recalculated on a surveillance 4DCT (sCT) acquired at fraction ten and robustness evaluation was performed to evaluate the effect of respiration and inter-fractional anatomical changes. ResultsAll PT and XT plans complied with V95%iCTVtotal >99% for the nominal plan and V95%iCTVtotal >97% for all respiratory and robustness scenarios. Lung and heart dose varied considerably between centres for both modalities. The difference in mean lung dose and mean heart dose between each pair of XT and PT plans was in median [range] 4.8 Gy [1.1;7.6] and 8.4 Gy [1.9;24.5], respectively. Patients B and C showed large inter-fractional anatomical changes on sCT. For patient B, the minimum V95%iCTVtotal in the worst-case robustness scenario was 45% and 94% for XT and PT, respectively. For patient C, the minimum V95%iCTVtotal was 57% and 72% for XT and PT, respectively. Patient A and D showed minor inter-fractional changes and the minimum V95%iCTVtotal was >85%. ConclusionLarge variability in dose to the lungs and heart was observed for both modalities. Inter-fractional anatomical changes led to larger target dose deterioration for XT than PT plans.

GPU-accelerated Monte Carlo-based online adaptive proton therapy: A feasibility study.

To develop an online graphic processing unit (GPU)-accelerated Monte Carlo-based adaptive radiation therapy (ART) workflow for pencil beam scanning (PBS) proton therapy to address interfraction anatomical changes in patients treated with PBS. A four-step workflow was developed using our in-house developed GPU-accelerated Monte Carlo-based treatment planning system to implement online Monte Carlo-based ART for PBS. The first step conducts diffeomorphic demon-based deformable image registration (DIR) to propagate contours on the initial planning CT (pCT) to the verification CT (vCT) to form a new structure set. The second step performs forward dose calculation of the initial plan on the vCT with the propagated contours after manual approval (possible modifications involved). The third step triggers a reoptimization of the plan depending on whether the verification dose meets the clinical requirements or not. A robust evaluation will be done for both the verification plan in the second step and the reopotimized plan in the third step. The fourth step involves a two-stage (before and after delivery) patient-specific quality assurance (PSQA) of the reoptimized plan. The before-delivery PSQA is to compare the plan dose to the dose calculated using an independent fast open-source Monte Carlo code, MCsquare. The after-delivery PSQA is to compare the plan dose to the dose recalculated using the log file (spot MU, spot position, and spot energy) collected during the delivery. Jaccard index (JI), dice similarity coefficients (DSCs), and Hausdorff distance (HD) were used to assess the quality of the propagated contours in the first step. A commercial plan evaluation software, ClearCheck™, was integrated into the workflow to carry out efficient plan evaluation. 3D Gamma analysis was used during the fourth step to ensure the accuracy of the plan dose from reoptimization. Three patients with three different disease sites were chosen to evaluate the feasibility of the online ART workflow for PBS. For all three patients, the propagated contours were found to have good volume conformance [JI (lowest-highest: 0.833-0.983) and DSC (0.909-0.992)] but suboptimal boundary coincidence [HD (2.37-20.76mm)] for organs-at-risk. The verification dose evaluated by ClearCheck™ showed significant degradation of the target coverage due to the interfractional anatomical changes. Reoptimization on the vCT resulted in great improvement of the plan quality to a clinically acceptable level. 3D Gamma analyses of PSQA confirmed the accuracy of the plan dose before delivery (mean Gamma index=98.74% with a threshold of 2%/2mm/10%), and after delivery based on the log files (mean Gamma index=99.05% with a threshold of 2%/2mm/10%). The average time cost for the complete execution of the workflow was around 858s, excluding the time for manual intervention. The proposed online ART workflow for PBS was demonstrated to be efficient and effective by generating a reoptimized plan that significantly improved the plan quality.

Dosimetric benefit of MR-guided online adaptive radiotherapy in different tumor entities: liver, lung, abdominal lymph nodes, pancreas and prostate

BackgroundHybrid magnetic resonance (MR)-Linac systems have recently been introduced into clinical practice. The systems allow online adaption of the treatment plan with the aim of compensating for interfractional anatomical changes. The aim of this study was to evaluate the dose volume histogram (DVH)-based dosimetric benefits of online adaptive MR-guided radiotherapy (oMRgRT) across different tumor entities and to investigate which subgroup of plans improved the most from adaption.MethodsFifty patients treated with oMRgRT for five different tumor entities (liver, lung, multiple abdominal lymph nodes, pancreas, and prostate) were included in this retrospective analysis. Various target volume (gross tumor volume GTV, clinical target volume CTV, and planning target volume PTV) and organs at risk (OAR) related DVH parameters were compared between the dose distributions before and after plan adaption.ResultsAll subgroups clearly benefited from online plan adaption in terms of improved PTV coverage. For the liver, lung and abdominal lymph nodes cases, a consistent improvement in GTV coverage was found, while many fractions of the prostate subgroup showed acceptable CTV coverage even before plan adaption. The largest median improvements in GTV near-minimum dose (D98%) were found for the liver (6.3%, p < 0.001), lung (3.9%, p < 0.001), and abdominal lymph nodes (6.8%, p < 0.001) subgroups. Regarding OAR sparing, the largest median OAR dose reduction during plan adaption was found for the pancreas subgroup (-87.0%). However, in the pancreas subgroup an optimal GTV coverage was not always achieved because sparing of OARs was prioritized.ConclusionWith online plan adaptation, it was possible to achieve significant improvements in target volume coverage and OAR sparing for various tumor entities and account for interfractional anatomical changes.

Image Performance Characterization of an In-Beam Low-Field Magnetic Resonance Imaging System During Static Proton Beam Irradiation

Image guidance using <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in-beam</i> real-time magnetic resonance (MR) imaging is expected to improve the targeting accuracy of proton therapy for moving tumors, by reducing treatment margins, detecting interfractional and intrafractional anatomical changes and enabling beam gating. The aim of this study is to quantitatively characterize the static magnetic field and image quality of a 0.22T open MR scanner that has been integrated with a static proton research beamline. The magnetic field and image quality studies are performed using high-precision magnetometry and standardized diagnostic image quality assessment protocols, respectively. The magnetic field homogeneity was found to be typical of the scanner used (98ppm). Operation of the beamline magnets changed the central resonance frequency and magnetic field homogeneity by a maximum of 16Hz and 3ppm, respectively. It was shown that the <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in-beam</i> MR scanner features sufficient image quality and influences of simultaneous irradiation on the images are restricted to a small sequence-dependent image translation (0.1–0.7mm) and a minor reduction in signal-to-noise ratio (1.3%–5.6%). Nevertheless, specific measures have to be taken to minimize these effects in order to achieve accurate and reproducible imaging which is required for a future clinical application of MR integrated proton therapy.

Technical challenges in the treatment of mediastinal lymphomas by proton pencil beam scanning and deep inspiration breath-hold

PurposeTo comprehensively describe the treatment of mediastinal lymphoma by pencil beam scanning (PBS) proton therapy. MethodsFourteen patients underwent PBS proton treatment in a supine position in deep inspiration breath-hold (DIBH). Three DIBH computed tomography (CT) scans were acquired for each patient to delineate the Internal Target Volume (ITV). Intensity-modulated proton therapy (IMPT) was planned by min–max robust optimization on the ITV, with a 6 mm setup and 3.5% range uncertainties. Robustness analysis was performed and dose coverage was visually inspected on the corresponding voxel-wise minimum map. Layer repainting was set equal to 5 to compensate for cardiac motion. Intra-fraction reproducibility during treatment was assessed by repeated daily DIBH X-ray imaging. Finally, an additional CT was acquired at half treatment to estimate the impact of inter-fraction dosimetric reproducibility. ResultsIMPT guaranteed robust mediastinal target coverage and organs-at-risk sparing. However, visual voxel-wise robustness evaluation showed that in five patients a second optimization with focused objectives in the cost-function was necessary to achieve a robust coverage of the target regions at the interface between lungs and soft tissue. In six patients, repainting was not used due to excessive treatment time length and poor patient compliance. Intra-fraction average reproducibility was within 1 mm/1degree. On repeated CT scans, inter-fraction setup errors and/or anatomical changes showed minimal dosimetric differences in CTV coverage. ConclusionIMPT in DIBH is effective and reproducible to treat mediastinal lymphomas. Caution is recommended to guarantee robust dose delivery to high-risk regions at the interface between lungs and soft tissue.

MR-guided SBRT boost for patients with locally advanced or recurrent gynecological cancers ineligible for brachytherapy: feasibility and early clinical experience

Background and purposeChemoradiotherapy (CRT) followed by a brachytherapy (BT) boost is the standard of care for patients with locally advanced or recurrent gynecological cancer (LARGC). However, not every patient is suitable for BT. Therefore, we investigated the feasibility of an MR-guided SBRT boost (MRg-SBRT boost) following CRT of the pelvis.Material and methodsTen patients with LARGC were analyzed retrospectively. The patients were not suitable for BT due to extensive infiltration of the pelvic wall (10%), other adjacent organs (30%), or both (50%), or ineligibility for anesthesia (10%). Online-adaptive treatment planning was performed to control for interfractional anatomical changes. Treatment parameters and toxicity were evaluated to assess the feasibility of MRg-SBRT boost.ResultsMRg-SBRT boost was delivered to a median total dose of 21.0 Gy in 4 fractions. The median optimized PTV (PTVopt) size was 43.5ccm. The median cumulative dose of 73.6Gy10 was delivered to PTVopt. The cumulative median D2ccm of the rectum was 63.7 Gy; bladder 72.2 Gy; sigmoid 65.8 Gy; bowel 59.9 Gy (EQD23). The median overall treatment time/fraction was 77 min, including the adaptive workflow in 100% of fractions. The median duration of the entire treatment was 50 days. After a median follow-up of 9 months, we observed no CTCAE ≥ °II toxicities.ConclusionThese early results report the feasibility of an MRg-SBRT boost approach in patients with LARGC, who were not candidates for BT. When classical BT-OAR constraints are followed, the therapy was well tolerated. Long-term follow-up is needed to validate the results.

Investigation of Suitable Detection Angles for Carbon-Ion Radiotherapy Monitoring in Depth by Means of Secondary-Ion Tracking.

The dose conformity of carbon-ion beam radiotherapy, which allows the reduction of the dose deposition in healthy tissue and the escalation of the dose to the tumor, is associated with a high sensitivity to anatomical changes during and between treatment irradiations. Thus, the monitoring of inter-fractional anatomical changes is crucial to ensure the dose conformity, to potentially reduce the size of the safety margins around the tumor and ultimately to reduce the irradiation of healthy tissue. To do so, monitoring methods of carbon-ion radiotherapy in depth using secondary-ion tracking are being investigated. In this work, the detection and localization of a small air cavity of 2 mm thickness were investigated at different detection angles of the mini-tracker relative to the beam axis. The experiments were conducted with a PMMA head phantom at the Heidelberg Ion-Beam Therapy Center (HIT) in Germany. In a clinic-like irradiation of a single field of 3 Gy (RBE), secondary-ion emission profiles were measured by a 2 cm2 mini-tracker composed of two silicon pixel detectors. Two positions of the cavity in the head phantom were studied: in front and in the middle of the tumor volume. The significance of the cavity detection was found to be increased at smaller detection angles, while the accuracy of the cavity localization was improved at larger detection angles. Detection angles of 20° – 30° were found to be a good compromise for accessing both, the detectability and the position of the air cavity along the depth in the head of a patient.

Use of in vivo transit portal images to detect gross inter-fraction patient geometry changes on an O-ring type linear accelerator for pelvis and head/neck patients

The purpose of this work was to investigate the use of the Varian Portal Dosimetry application in conjunction with in vivo megavoltage portal images on a Varian Halcyon O-ring type linear accelerator as an in vivo dosimetry constancy (IVDc) tool for pelvis and head/neck patients receiving VMAT treatments. Sensitivity testing was conducted on phantoms with varying thicknesses (0.2 cm–1.0 cm) using static and modulated fields. A cohort of 96 portal dose images across eight patients was then compared with PTV metrics derived from daily CBCT image based treatment plan re-calculations to determine whether the IVDc tool could detect gross inter-fraction anatomical changes. A final cohort of 315 portal dose images across 22 patients was then assessed to demonstrate the application of IVDc tool. The IVDc tool, using 2%/2 mm criteria, detected all phantom thickness changes of 1.0 cm, some phantom thickness changes of 0.5 cm, and no changes of 0.2 cm. For the cohort of 96 results, a IVDc passing criteria of 95% (2%, 2 mm) was able to identify all cases that had PTV metric changes of 2% or more. Using the IVDc tool on the cohort of 315 results, and the IVDc passing criteria of 95%, resulted in 74 IVDc failures. A simple, easy to implement, methodology has been presented that is capable of detecting gross inter-fraction changes in patient geometry on the Varian Halcyon O-ring linac linear accelerator.

Dosimetric Uncertainties Resulting From Interfractional Anatomic Variations for Patients Receiving Pancreas Stereotactic Body Radiation Therapy and Cone Beam Computed Tomography Image Guidance

PurposeTo estimate the effects of interfractional anatomic changes on dose to organs at risk (OARs) and tumors, as measured with cone beam computed tomography (CBCT) image guidance for pancreatic stereotactic body radiation therapy. Methods and MaterialsWe evaluated 11 patients with pancreatic cancer whom were treated with stereotactic body radiation therapy (33-40 Gy in 5 fractions) using daily CT-on-rails (CTOR) image guidance immediately before treatment with breath-hold motion management. CBCT alignment was simulated in the treatment planning software by aligning the original planning CT to each fractional CTOR image set via fiducial markers. CTOR data sets were used to calculate fractional doses after alignment by applying the rigid shift of the planning CT and CTOR image sets to the planning treatment isocenter and recalculating the fractional dose. Accumulated dose to the gross tumor volume (GTV), tumor vessel interface, duodenum, small bowel, and stomach were calculated by summing the 5 fractional absolute dose-volume histograms into a single dose-volume histogram for comparison with the original planned dose. ResultsFour patients had a GTV D100% of at least 1.5 Gy less than the fractional planned value in several fractions; 4 patients had fractional underestimation of duodenum dose by 1.0 Gy per fraction. The D1.0 cm3 <35 Gy constraint was violated for at least 1 OAR in 3 patients, with either the duodenum (n = 2) or small bowel (n = 1) D1.0 cm3 being higher on the accumulated dose distribution (P = .01). D100% was significantly lower according to accumulated dose GTV (P = .01) and tumor vessel interface (P = .02), with 4 and 2 patients having accumulated D100% ≥4 Gy lower than the planned value for the GTV and tumor vessel interface, respectively. ConclusionsFor some patients, CBCT image guidance based on fiducial alignment may cause large dosimetric uncertainties for OARs and target structures, according to accumulated dose.

Feasibility and Early Clinical Experience of Online Adaptive MR-Guided Radiotherapy of Liver Tumors.

Simple SummaryStereotactic body radiotherapy is used in the treatment of liver tumors. However, adjacent organs at risk (OAR) frequently limit the applicable dose to the target volume. The introduction of hybrid magnetic resonance imaging (MRI)-guided radiotherapy systems may allow dose escalation strategies with better OAR sparing due to improved soft tissue visualization, adaptive treatment planning and real-time motion management. Here we report the feasibility and early results of online adaptive MR-guided radiotherapy of primary and secondary liver tumors in eleven patients. The treatment was feasible and successfully completed in all patients. After a median follow-up of five months, no local failure occurred and no ≥ grade 2 toxicity was observed. The technique should be compared to conventional SBRT in further studies to assess the advantages of the technique.Purpose: To assess the feasibility and early results of online adaptive MR-guided radiotherapy (oMRgRT) of liver tumors. Methods: We retrospectively examined consecutive patients with primary or secondary liver lesions treated at our institution using a 0.35T hybrid MR-Linac (Viewray Inc., Mountain View, CA, USA). Online-adaptive treatment planning was used to account for interfractional anatomical changes, and real-time intrafractional motion management using online 2D cine MRI was performed using a respiratory gating approach. Treatment response and toxicity were assessed during follow-up. Results: Eleven patients and a total of 15 lesions were evaluated. Histologies included cholangiocarcinomas and metastases of neuroendocrine tumors, colorectal carcinomas, sarcomas and a gastrointestinal stroma tumor. The median BED10 of the PTV prescription doses was 84.4 Gy (range 59.5–112.5 Gy) applied in 3–5 fractions and the mean GTV BED10 was in median 147.9 Gy (range 71.7–200.5 Gy). Online plan adaptation was performed in 98% of fractions. The median overall treatment duration was 53 min. The treatment was feasible and successfully completed in all patients. After a median follow-up of five months, no local failure occurred and no ≥ grade two toxicity was observed. OMRgRT resulted in better PTV coverage and fewer OAR constraint violations. Conclusion: Early results of MR-linac based oMRgRT for the primary and secondary liver tumors are promising. The treatment was feasible in all cases and well tolerated with minimal toxicity. The technique should be compared to conventional SBRT in further studies to assess the advantages of the technique.

Accounting for prompt gamma emission and detection for range verification in proton therapy treatment planning

Prompt gamma (PG) imaging is widely investigated as one of the most promising methods for proton range verification in proton therapy. The performance of this technique is affected by several factors like tissue heterogeneity, number of protons in the considered pencil beam and the detection device. Our previous work proposed a new treatment planning concept which boosts the number of protons of a few PG monitoring-friendly pencil beams (PBs), selected on the basis of two proposed indicators quantifying the conformity between the dose and PG at the emission level, above the desired detectability threshold. To further explore this method at the detection level, in this work we investigated the response of a knife-edge slit PG camera which was deployed in the first clinical application of PG to proton therapy monitoring. The REGistration Graphical User Interface (REGGUI) is employed to simulate the PG emission, PG detection as well as the corresponding dose distribution. As the PG signal detected by this kind of PG camera is sensitive to the relative position of the camera and PG signal falloff, we optimized our PB selection method for this camera by introducing a new camera position indicator identifying whether the expected falloff of the PG signal is centered in the field of view of the camera or not. Our camera-adapted PB selection method is investigated using computed tomography (CT) scans at two different treatment time points of a head and neck, and a prostate cancer patient under scenarios considering different statistics level. The results show that a precision of 0.8 mm for PG falloff identification can be achieved when a PB has more than 2 × 108 primary protons. Except for one case due to unpredictable and comparably large anatomical changes, the PG signals of most of the PBs recommended by all our indicators are observed to be reliable for proton range verification with deviations between the inter-fractional shift of proton range (as deduced from the PB dose distribution) and the detected PG signal within 2.0 mm. In contrast, a shift difference up to 9.6 mm has been observed for the rejected PBs. The magnitude of the proton range shift due to the inter-fractional anatomical changes is observed to be up to 23 mm. The proposed indicators are shown to be valuable for identifying and recommending reliable PBs to create new PG monitoring-friendly TPs. Comparison between our PB boosting method and the alternative PB aggregation, which combines the signal of nearby PBs to reach the desired counting statistics, is also discussed.

Robustness of daily dose for each beam angle and accumulated dose for inter-fractional anatomical changes in passive carbon-ion radiotherapy for pancreatic cancer: Bone matching versus tumor matching

PurposeWe aimed to assess the robustness of accumulated dose distributions for inter-fractional changes in passive carbon-ion radiotherapy for pancreatic cancer. MethodsNinety-five daily CT image sets acquired after the treatment of eight patients with pancreatic cancer were used in this prospective study. Dose distributions with treatment beam fields were recalculated for bone matching (BM) and tumor matching (TM) positions on all daily CT images, the accumulated doses being calculated using deformable image registration methods. The prescribed dose was 55.2 Gy (relative biological effectiveness [RBE]) in 12 fractions. Dose volume parameters of V95 (%) for CTV and GTV, and D2cc (Gy(RBE)) for the stomach and duodenum were evaluated. ResultsThe medians (range) of CTV V95 (%) were 91.9 (86.1–100.0), 80.5 (56.1–90.6), and 86.4 (72.5–96.5) for the Plan, accumulated with BM and TM, respectively; GTV values (%) were 98.0 (85.7–100.0), 93.3 (65.7–99.9), and 96.2 (84.8–100.0), respectively. There were significant differences between all combinations apart from the Plan and TM for both targets. The values of stomach D2cc (Gy(RBE)) were 36.0 (16.9–43.4), 36.7 (17.9–45.0), and 35.2 (16.8–43.5), respectively; duodenum values (Gy(RBE)) were 25.2 (21.3–40.3), 30.1 (23.3–48.6), and 28.3 (20.4–50.6), respectively. There was a significant difference between the Plan and BM for duodenum only. ConclusionsTM is recommended over BM because it can achieve higher target dose coverage than BM. Nevertheless, it is not enough in some cases. Further technical improvements are necessary to improve the target dose coverage.

A Preliminary Simulation Study of Dose-Guided Adaptive Radiotherapy Based on Halcyon MV Cone-Beam CT Images With Retrospective Data From a Phase II Clinical Trial.

Background and purpose: To evaluate the feasibility of dose-guided adaptive radiotherapy (ART) based on deformable image registration (DIR) using fractional megavoltage cone-beam CT (MVCBCT) images from Halcyon system that uses identical beams for treatment and imaging and to retrospectively investigate the influence of anatomic changes on target coverage and organ-at-risk (OAR) sparing across various tumor sites.Materials and Methods: Four hundred twenty-two MVCBCT images from 16 patients (three head and neck, seven thoracic, three abdominal, and three pelvic cases) treated in a phase II clinical trial for Halcyon were selected. DIR between the planning CT and daily MVCBCT image was implemented by Velocity software to create pseudo CT. To investigate the accuracy of dose calculation on pseudo CT, three evaluation patients with rescanned CT and adaptive plans were selected. Dose distribution of adaptive plans calculated on pseudo CT was compared with that calculated on the rescanned planning CT on the three evaluation patients. To investigate the impact of inter-fractional anatomic changes on target dose coverage and dose to OARs of the 16 patients, fractional dose was calculated and accumulated incrementally based on deformable registration between planning CT and daily MVCBCT images.Results: Passing rates using 3 mm/3%/10% threshold local gamma analysis were 93.04, 96.00, and 91.68%, respectively, for the three evaluation patients between the reconstructed dose on pseudo CT (MVCBCT) and rescanned CT, where accumulated dose deviations of over 97% voxels were smaller than 0.5 Gy. Planning target volume (PTV) D95% and D90% (the minimum dose received by at least 95/90% of the volume) of the accumulated dose could be as low as 93.8 and 94.5% of the planned dose, respectively. OAR overdose of various degrees were observed in the 16 patients relative to the planned dose. In most cases, OARs' dose volume histogram (DVH) lines of accumulated and planned dose were very close to each other if not overlapping. Among cases with visible deviations, the differences were bilateral without apparent patterns specific to tumor sites or organs.Conclusion: As a confidence building measure, this simulation study suggested the possibility of ART for Halcyon based on DIR between planning CT and MVCBCT. Preliminary clinical data suggested the benefit of patient-specific dose reconstruction and ART to avoid unacceptable target underdosage and OAR overdosage.

Assessment of online adaptive MR-guided stereotactic body radiotherapy of liver cancers.

Online Adaptive Radiotherapy (ART) with daily MR-imaging has the potential to improve dosimetric accuracy by accounting for inter-fractional anatomical changes. This study provides an assessment for the feasibility and potential benefits of online adaptive MRI-Guided Stereotactic Body Radiotherapy (SBRT) for treatment of liver cancer. Ten patients with liver cancer treated with MR-Guided SBRT were included. Prescription doses ranged between 27 and 50Gy in 3-5 fx. All SBRT fractions employed daily MR-guided setup while utilizing cine-MR gating. Organs-at-risk (OARs) included duodenum, bowel, stomach, kidneys and spinal cord. Daily MRIs and contours were utilized to create each adapted plan. Adapted plans used the beam-parameters and optimization-objectives from the initial plan. Planning target volume (PTV) coverage and OAR constraints were used to compare non-adaptive and adaptive plans. PTV coverage for non-adapted treatment plans was below the prescribed coverage for 32/47 fractions (68%), with 11 fractions failing by more than 10%. All 47 adapted fractions met prescribed coverage. OAR constraint violations were also compared for several organs. The duodenum exceeded tolerance for 5/23 non-adapted and 0/23 for adapted fractions. The bowel exceeded tolerance for 5/34 non-adaptive and 1/34 adaptive fractions. The stomach exceeded tolerance for 4/19 non-adapted and 1/19 for adaptive fractions. Accumulated dose volume histograms were also generated for each patient. Online adaptive MR-Guided SBRT of liver cancer using daily re-optimization resulted in better target conformality, coverage and OAR sparing compared with non-adaptive SBRT. Daily adaptive planning may allow for PTV dose escalation without compromising OAR sparing.

Impact of Inter-fractional Anatomical Changes on Dose Distributions in Passive Carbon-Ion Radiotherapy for Prostate Cancer: Comparison of Vertical and Horizontal Fields.

Purpose: We quantified the inter-fractional changes associated with passive carbon-ion radiotherapy using vertical and horizontal beam fields for prostate cancer.Methods: In total, 118 treatment-room computed tomography (TRCT) image sets were acquired from 10 patients. Vertical (anterior–posterior) and horizontal (left–right) fields were generated on the planning target volume identified by treatment planning CT. The dose distribution for each field was recalculated on each TRCT image set at the bone-matching position and evaluated using the dose–volume parameters for the prostate and rectum V95 values. To confirm adequate margins, we generated vertical and horizontal fields with 0-, 2-, 4-, and 6-mm isotropic margins from the prostate and recalculated the dose distributions on all TRCT image sets. Sigmoid functions were fitted to a plot of acceptable ratios (that is, when prostate V95 > 98%) vs. the isotropic margin size to identify the margin at which this ratio was achieved in 95% of patients with a vertical or horizontal field.Results: The prostate V95 values (mean ± standard deviation) were 99.89 ± 0.62% and 99.99 ± 0.00% with vertical and horizontal fields, respectively; this difference was not statistically significant (p = 0.067). The rectum V95 values were 1.93 ± 1.25 and 1.88 ± 0.96 ml with vertical and horizontal fields, respectively; the difference was not statistically significant (p = 0.432). The estimated adequate margins were 2.2 and 3.0 mm for vertical and horizontal fields, respectively.Conclusions: Although there is no significant difference, horizontal fields offer higher reproducibility for prostate dosing than vertical fields in our clinical setting, and 3.0 mm was found to be an adequate margin for inter-fractional changes.

Patterns of practice for adaptive and real-time radiation therapy (POP-ART RT) part I: Intra-fraction breathing motion management

PurposeThe POP-ART RT study aims to determine to what extent and how intra-fractional real-time respiratory motion management (RRMM) and plan adaptation for inter-fractional anatomical changes (ART), are used in clinical practice and to understand barriers to implementation. Here we report on part I: RRMM. Material and methodsA questionnaire was distributed worldwide to assess current clinical practice, wishes for expansion or new implementation and barriers to implementation.RRMM was defined as inspiration/expiration gating in free-breathing or breath-hold, or tracking where the target and the beam are continuously realigned. ResultsThe questionnaire was completed by 200 centres from 41 countries. RRMM was used by 68% of respondents (‘users’) for a median (range) of 2 (1–6) tumour sites.Eighty-one percent of users applied inspiration breath-hold in at least one tumour site (breast: 96%). External marker was used to guide RRMM by 61% of users. KV/MV imaging was frequently used for liver and pancreas (with fiducials) and for lung (with or without fiducials). Tracking was mainly performed on robotic linacs with hybrid internal-external monitoring.For breast and lung, approximately 75% of respondents used or wished to implement RRMM, which was lower for liver (44%) and pancreas (27%). Seventy-one percent of respondents wished to implement RRMM for a new tumour site. Main barriers were human/financial resources and capacity on the machine. ConclusionSixty-eight percent of respondents used RRMM and 71% wished to implement RRMM for a new tumour site. The main barriers to implementation were human/financial resources and capacity on treatment machines.

Patterns of practice for adaptive and real-time radiation therapy (POP-ART RT) part II: Offline and online plan adaption for interfractional changes

PurposeThe POP-ART RT study aims to determine to what extent and how intrafractional real-time respiratory motion management (RRMM), and plan adaptation for interfractional anatomical changes (ART) are used in clinical practice and to understand barriers to implementation. Here we report on part II: ART using more than one plan per target per treatment course. Materials and methodsA questionnaire on the current practice of ART, wishes for expansion or implementation, and barriers to implementation was distributed worldwide. Four types of ART were discriminated: daily online replanning, online plan library, protocolled offline replanning (all three based on a protocol), and ad-hoc offline replanning. ResultsThe questionnaire was completed by 177 centres from 40 countries. ART was used by 61% of respondents (31% with protocol) for a median (range) of 3 (1–8) tumour sites. CBCT/MVCT was the main imaging modality except for online daily replanning (11 users) where 10 users used MR. Two thirds of respondents wished to implement ART for a new tumour site; 40% of these had plans to do it in the next 2 years. Human/material resources and technical limitations were the main barriers to further use and implementation. ConclusionsART was used for a broad range of tumour sites, mainly with ad-hoc offline replanning and for a median of 3 tumour sites. There was a large interest in implementing ART for more tumour sites, mainly limited by human/material resources and technical limitations. Daily online replanning was primarily performed on MR-linacs.

Evaluation of daily dose accumulation with deformable image registration method using helical tomotherapy images for nasopharyngeal carcinoma

AbstractAim:Nasopharyngeal carcinoma (NPC) patients may have anatomical variations during their radiotherapy treatment course. In this study, we determine the daily accumulated dose by the deformable image registration (DIR) process for comparing with the planned dose and explore the number of fractions which the daily accumulated dose significantly changed from the planned dose.Methods:The validation of the DIR process in MIM software has been tested. One hundred and sixty-five daily megavoltage computed tomography (MVCT) images of NPC patients who were treated by helical tomotherapy were exported to MIM software to determine the daily accumulated dose and then compared with the planned dose.Results:The MIM software illustrated the acceptable validation for clinical application. The accumulated dose (D50%) of the planning target volume (PTV70) showed a decrease from the planned dose with an average of 0.5 ± 0.27% at the end of the treatment and was significantly different from the planned dose after the second fraction of the treatment (p-value = 0.008). In contrast, the accumulated dose of organ at risk (OAR) tended to increase from the planned dose and was significantly different after the fifth fraction (left parotid), the twelfth fraction (right parotid) and the second fraction (spinal cord).Findings:The inter-fractional anatomic changes cause the actual dose to be different from the planned dose. The dose differences and the number of fractions were varied in each target and OAR. The dose accumulation explored the necessary information for the radiation oncologist to consider adaptive treatment strategies to increase the efficiency of treatment.

Impact of interfractional anatomical variation and setup correction methods on interfractional dose variation in IMPT and VMAT plans for pancreatic cancer patients: A planning study.

PurposeTo investigate the impact of interfractional anatomical changes and setup correction methods on dose distributions in pancreatic cancer patients under breath‐hold conditions.MethodsThree intensity‐modulated proton therapy (IMPT) plans with different beam arrangements and one volumetric‐modulated arc therapy (VMAT) plan prescribing 54 Gy in 30 fractions were created for 10 patients who underwent three additional CT scans performed at an interval of 1–2 weeks. The additional CT sets were rigidly registered to the simulation CT set using both bone‐matching (BM) and organ‐matching (OM) methods in each patient. Recalculated dose distributions and dose–volume indices on the additional CT sets using either the BM or the OM method were compared with the simulation values.ResultsDifferences in the gross tumor volume D98% value from the simulation sets ranged from −0.8 to −5.9% on average. In addition, the variations were larger with OM compared with BM for two IMPT plans. Meanwhile, differences in the D98% value in the region isotropically enlarged by 5 mm from the gross tumor volume were significantly improved with OM on two IMPT plans and the VMAT plan. Among the organs at risk, the dose–volume indices were significantly improved with OM only in the duodenum on all plans.ConclusionOrgan‐matching may be a better setup correction technique than BM for both photon therapy and IMPT plans. However, in some beam arrangements of IMPT, the dose distribution may be somewhat worse using OM, due to interfractional anatomical variation. Therefore, it is important to choose beam angles that are less likely to be influenced by changes in the gastrointestinal gas volume, especially in IMPT plans.

A new treatment planning approach accounting for prompt gamma range verification and interfractional anatomical changes

Prompt gamma (PG) imaging is widely investigated for spot-by-spot in vivo range verification for proton therapy. Previous studies pointed out that the accuracy of prompt gamma imaging is affected by the statistics (number of protons delivered per pencil beam) of the proton beams and the conformity between prompt gamma and dose distribution (PG-dose correlation). Recently a novel approach to re-optimize conventional treatment plans by boosting a few pencil beams with good PG-dose correlation above the statistics limit for reliable PG detectability was proposed. However, up to now, only PG-dose correlation on the planning computed tomography (CT) was considered, not accounting for the fact that the robustness of the PG-dose correlation is not guaranteed in the cases of interfractional anatomical changes. In this work, this approach is further explored with respect to the robustness of the PG-dose correlation of each pencil beam in the case of interfractional anatomical changes. A research computational platform, combining Monte Carlo pre-calculated pencil beams with the analytical Matlab-based treatment planning system (TPS) CERR, is used for treatment planning. Geant4 is used for realistic simulation of the dose delivery and PG generation for all individual pencil beams in the heterogeneous patient anatomy using multiple CT images for representative patient cases (in this work, CTs of one prostate and one head and neck cancer patient are used). First, a Monte Carlo treatment plan is created using CERR. Thereby the PG emission and dose distribution for each individual spot is obtained. Second, PG-dose correlation is quantified using the originally proposed approach as well as a new indicator, which accounts for the sensitivity of individual spots to heterogeneities in the 3D dose distribution. This is accomplished by using a 2D distal surface (dose surface) derived from the 3D dose distribution for each spot. A few pencil beams are selected for each treatment field, based on their PG-dose correlation and dose surface, and then boosted in the new re-optimized treatment plan. All treatment plans are then fully re-calculated with Monte Carlo on the CT scans of the corresponding patient at three different time points. The result shows that all treatment plans are comparable in terms of dose distribution and dose averaged LET distributions. The spots recommended by our indicators maintain good PG-dose correlation in the cases of interfractional anatomical changes, thus ensuring that the proton range shift due to anatomical changes can be monitored. Compared to another proposed spots aggregation approach, our approach shows advantages in terms of the detectability and reliability of PG, especially in presence of heterogeneities.