Interfractional Variations Research Articles

Optimising PTV margins in oesophageal cancer radiotherapy: Amodern radiotherapy planning, treatment delivery and verification approach - A single institutional analysis.

Radiotherapy plays a key role in the multidisciplinary management of oesophageal cancers across neoadjuvant, definitive and palliative settings. Improved precision in radiotherapy planning and delivery techniques have allowed treating disease with tighter margins reducing toxicity. In this study, we examine the appropriateness of current practice in defining the planning target volume (PTV). This is a single institutional retrospective study of patients who received radiotherapy for oesophageal cancers using volumetric modulated arc therapy (VMAT) during 2020. All cone-beam computerised tomography (CBCT) scans were reviewed to assess whether PTV expansions appropriately accounted for tumour motion and interfractional variation. Of the 27 patients, 2 (7%), 5 (19%) and 20 (74%) had cervical, thoracic and distal/gastro-oesophageal junction (GOJ) disease, respectively. 16 (59%) had adenocarcinoma and 9 (33%) had squamous cell carcinoma. 9 of 20 distal/GOJ patients were planned and treated according to the institutional stomach filling protocol. 521/528 (98.7%) CBCTs demonstrated adequate target coverage. Cervical, thoracic and GOJ regions demonstrated adequate target coverage in 57/58, 96/97 and 368/373 CBCTs with median PTV expansions of 5, 7 and 7 mm, respectively. In four patients with GOJ disease, CBCT review identified five episodes where the target volume was insufficiently covered during the treatment course. In this single institutional retrospective study, for the vast majority of patients, our institutional practice of defining PTV margins achieved satisfactory target treatment. The interfractional variations observed in patients with GOJ tumours due to target motion and variable gastric volume, highlights the role of further refinements to motion management techniques in this cohort.

Prospective Trial on the Impact of Weekly Cone Beam Computed Tomography-Guided Correction on Mean Heart Dose in Breast Cancer Breath-Hold Radiation Therapy

PurposeSurface-guided radiotherapy (SGRT) in breast cancer radiotherapy (RT) may decrease the need for image guidance such as cone beam computed tomography (CBCT). The goal of this study is to evaluate the impact of CBCT image guidance on the cumulative and interfractional variation of mean heart dose (MHD) during breath-hold radiotherapy in patients with breast cancer. We hypothesize that weekly CBCT is not necessary in SGRT-assisted breath-hold, but is still needed in patients treated with voluntary deep inspiration breath hold (vDIBH) and active breathing control (ABC) to maintain a stable MHD. Methods and materialsThis is a prospective, single-centre trial that sequentially assigned breast cancer patients to adjuvant RT 40-50Gy in 15-25 fractions using vDIBH, ABC or SGRT to reproduce the breath-hold. The MHD was estimated on each of the weekly CBCT images before and after online correction. The cumulative and interfractional variation of MHD, which were represented by the average and standard deviation (SD) of MHD in each patient, were compared in the series of CBCT before and after online correction, to evaluate whether online CBCT-guided correction could lead to a more reproducible MHD. ResultsFifty-five patients were included (vDIBH=16, ABC=19, SGRT=20). CBCT-guided online correction was associated with a significant decrease in the interfractional variation of MHD in vDIBH (SD difference: 22.6cGy, p=0.0389) and ABC (SD difference: 9.9cGy, p=0.0262), but not in SGRT (p=0.2272). CBCT-guided online correction had no impact on the cumulative MHD in all three groups. ConclusionsThis study demonstrated that CBCT-guided online correction could reduce the interfractional variation of MHD in ABC or vDIBH. When SGRT was available, CBCT-guided correction had no impact on the stability of MHD across the treatment fractions. Future studies may explore whether the CBCT frequency could be reduced to less than weekly in SGRT, to decrease treatment time and the radiation dose associated with CBCT.

Investigation of interfractional range variation owing to anatomical changes with beam directions based on water equivalent thickness in proton therapy for pancreatic cancer.

To assess the interfractional anatomical range variations (ARVs) with beam directions and their impact on dose distribution in intensity modulated proton therapy, we analyzed water equivalent thickness (WET) from 10 patients with pancreatic cancer. The distributions of the interfractional WET difference ($\Delta{\mathrm{WET}}^{\theta }$) across 360° were visualized using polar histograms. Interfractional ARVs were evaluated using the mean absolute error and ΔWET pass rate, indicating the percentage of $\Delta \mathrm{WE}{\mathrm{T}}^{\theta }$ < thresholds. The impact on dose distribution in proton therapy was evaluated based on two treatment plans for 40Gy(RBE)/5 fractions: 'Plan A', using two beam angles, in which the target was closest to the body surface among four perpendicular directions; and 'Plan B', using two beam angles with small ARVs. Analysis revealed individual variations in angular trends of interfractional ARVs. Three distinct trends were identified: Group 1 exhibited small ARVs around posterior directions; Group 2 exhibited small ARVs except ~60°; Group 3 demonstrated minimal ARVs only ~90°. In dose evaluation, while 150° and 210° were selected in Plan B for 9 out of 10 patients, for the remaining patient, 60° and 90° were chosen. Comparing dose volume histogram parameters for all patients, Plan B significantly reduced target coverage loss while maintaining organ-at-risk sparing comparable to Plan A. These results demonstrated that selecting beam angles with small interfractional ARVs for each patient enhances the robustness of dose distribution, reducing target coverage loss.

Dealing with rectum motion during radiotherapy: How can we anticipate it?

IntroductionIntra- and inter-fraction rectum motion is important for pelvic radiotherapy (RT). This study assesses how RT session duration, the presence or the absence of an intra-rectal tumour, and the distance from the anorectal junction (ARJd) impact rectal motion. Materials and methodsAnalyses used cone-beam computed tomographies (CBCTs) from RT patients treated for rectal and prostate cancer. Three structures were evaluated: (1) the entire rectum in patients without a rectal tumour (RectumProstate); (2) the non-invaded portion (RectumRectum) and (3) the tumour-invaded portion (RectumTumour) in rectal cancer patients.Intrafraction motion was assessed using the Hausdorff distance 95% and the Mean distance-to-agreement between structures delineated on the first CBCT and the 2 subsequent CBCTs within a same RT session. Interfraction motion was quantified by comparing structures delineated on the planning-CT and the first CBCT of each session.Linear mixed model evaluated rectum motion in relation to time, tumour presence, and ARJd, respectively. ResultsWe included 10 patients with and 10 without rectal cancer, collecting 385 CBCTs. A significant correlation (p < 0.05) between rectum motion and RT session duration was found. Intrafraction motion was significantly higher in prostate cancer patients (RectumProstate motion > RectumRectum and RectumTumour, p < 0.01). For interfraction motion, only the mean distance to agreement was significantly higher for RectumProstate (p < 0.05). Motion increased significantly with ARJd for all three structures (p < 0.001). ConclusionsSession duration, absence of a tumour, and ARJd are associated with larger intra- and interfraction rectal motion. This highlights the need for tailored RT treatment, including online-adaptive RT, to manage intra- and interfraction variations. Rectal motion should be handled differently for patients with prostate cancer and those with rectal cancer.

Treatment Time and Dosimetric Advantage in Cone Beam Computed Tomography-Guided Online Adaptive Radiation Therapy Considering Interfractional and Intrafractional Changes in Patients With Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

Radiation therapy is the standard treatment for localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The ETHOS system (Varian Medical System) has enabled us to perform cone beam computed tomography (CBCT)-guided online adaptive radiation therapy (oART). This study presents a retrospective dosimetric analysis for interfractional and intrafractional change and treatment time in oART for gastric MALT lymphoma. We included 3 male patients with gastric MALT lymphoma who underwent exhalation breath-hold fasting oART using the SpiroDynr'X system. Treatment details and plans (3 reference [REF] plans, 51 scheduled [SCH] plans, and adapted [ADP] plans) were retrospectively analyzed. Doses to the clinical target volume in planning CT (CTV_REF), CTV1, and CTV2 (representing the stomach in planning and preirradiation CBCT, respectively) and planning target volume (PTV) in the planning CBCT were estimated. D2%, D98%, D50%, and Dmean for these volumes, along with organ-at-risk doses, were examined across the 3 plans. The PTV dose coverage of CTV2 on preirradiation CBCT was calculated. CBCT-guided oART was completed within the scheduled period, using the ADP plans instead of the SCH plans on each treatment day in all cases. The average treatment time was approximately 45 minutes. CTV1 and CTV2 exhibited intrafractional and interfractional variations, fluctuating above and below CTV_REF. Some ADP plans resulted in incomplete PTV coverage of CTV2, but the unincluded volume was <1% of CTV2. D50%, D98%, and Dmean of CTV1, CTV2, and PTV were significantly improved in the ADP plans than in the SCH plans. Moreover, the Dmean to the liver and kidneys was reduced in the ADP plans. CBCT-guided oART in patients with gastric MALT lymphoma demonstrated that ADP plans improved CTV1, CTV2, and PTV doses and reduced the mean bilateral kidney and liver doses, suggesting that it may offer enhanced treatment precision for gastric MALT lymphoma.

Multi-institutional experimental validation of online adaptive proton therapy workflows

Objective. To experimentally validate two online adaptive proton therapy (APT) workflows using Gafchromic EBT3 films and optically stimulated luminescent dosimeters (OSLDs) in an anthropomorphic head-and-neck phantom. Approach. A three-field proton plan was optimized on the planning CT of the head-and-neck phantom with 2.0 Gy(RBE) per fraction prescribed to the clinical target volume. Four fractions were simulated by varying the internal anatomy of the phantom. Three distinct methods were delivered: daily APT researched by the Paul Scherrer Institute (DAPTPSI), online adaptation researched by the Massachusetts General Hospital (OAMGH), and a non-adaptive (NA) workflow. All methods were implemented and measured at PSI. DAPTPSI performed full online replanning based on analytical dose calculation, optimizing to the same objectives as the initial treatment plan. OAMGH performed Monte-Carlo-based online plan adaptation by only changing the fluences of a subset of proton beamlets, mimicking the planned dose distribution. NA delivered the initial plan with a couch-shift correction based on in-room imaging. For all 12 deliveries, two films and two sets of OSLDs were placed at different locations in the phantom. Main results. Both adaptive methods showed improved dosimetric results compared to NA. For film measurements in the presence of anatomical variations, the [min-max] gamma pass rates (3%/3 mm) between measured and clinically approved doses were [91.5%–96.1%], [94.0%–95.8%], and [67.2%–93.1%] for DAPTPSI, OAMGH, and NA, respectively. The OSLDs confirmed the dose calculations in terms of absolute dosimetry. Between the two adaptive workflows, OAMGH showed improved target coverage, while DAPTPSI showed improved normal tissue sparing, particularly relevant for the brainstem. Significance. This is the first multi-institutional study to experimentally validate two different concepts with respect to online APT workflows. It highlights their respective dosimetric advantages, particularly in managing interfractional variations in patient anatomy that cannot be addressed by non-adaptive methods, such as internal anatomy changes.

Rectal volume is correlated with interfractional positional shifts of the prostate gland in dogs receiving radiation therapy.

Variability in prostate gland positioning during RT for prostate tumors is a recognized challenge in both human and veterinary oncology. This retrospective study investigates the interfractional variability in prostate gland positioning in relation to rectal and bladder volumes in dogs undergoing radiation therapy (RT) for prostate tumors. The study tracked 10 dogs undergoing five RT sessions from February 2016 to November 2021, delivering a total of 25Gy each. Each dog underwent CT scans for treatment simulation, and cone-beam CT (CBCT) images were acquired before each RT. The focus was to analyze the positional shifts of the prostate gland concerning the volumes of the rectum and urinary bladder. The pelvic bones were used as the point of reference. The rectal and bladder volumes were measured before each RT, and shifts in the prostate gland position were calculated by comparing coordinates from planning CT and treatment session images. Findings revealed significant correlations between prostate positional shifts in the dorsal-ventral (repeated measures correlation coefficient of -0.58 [range 00.75-00.33]; P<.001) and cranial-caudal directions (repeated measures correlation coefficient [95%CI] 0.56 [range 0.31-0.74]; P<.001) and rectal volume, while no significant relationship was observed with bladder volume. Shifts in the lateral direction were not correlated with either organ's volume. This study highlights the importance of considering rectal volume in canine prostate tumor RT to minimize positional uncertainties. Maintaining consistent rectal volume may enhance the precision of prostate targeting, potentially influencing the safety of RT.

CBCT-DRRs superior to CT-DRRs for target-tracking applications for pancreatic SBRT

Objective. In current radiograph-based intra-fraction markerless target-tracking, digitally reconstructed radiographs (DRRs) from planning CTs (CT-DRRs) are often used to train deep learning models that extract information from the intra-fraction radiographs acquired during treatment. Traditional DRR algorithms were designed for patient alignment (i.e. bone matching) and may not replicate the radiographic image quality of intra-fraction radiographs at treatment. Hypothetically, generating DRRs from pre-treatment Cone-Beam CTs (CBCT-DRRs) with DRR algorithms incorporating physical modelling of on-board-imagers (OBIs) could improve the similarity between intra-fraction radiographs and DRRs by eliminating inter-fraction variation and reducing image-quality mismatches between radiographs and DRRs. In this study, we test the two hypotheses that intra-fraction radiographs are more similar to CBCT-DRRs than CT-DRRs, and that intra-fraction radiographs are more similar to DRRs from algorithms incorporating physical models of OBI components than DRRs from algorithms omitting these models. Approach. DRRs were generated from CBCT and CT image sets collected from 20 patients undergoing pancreas stereotactic body radiotherapy. CBCT-DRRs and CT-DRRs were generated replicating the treatment position of patients and the OBI geometry during intra-fraction radiograph acquisition. To investigate whether the modelling of physical OBI components influenced radiograph-DRR similarity, four DRR algorithms were applied for the generation of CBCT-DRRs and CT-DRRs, incorporating and omitting different combinations of OBI component models. The four DRR algorithms were: a traditional DRR algorithm, a DRR algorithm with source-spectrum modelling, a DRR algorithm with source-spectrum and detector modelling, and a DRR algorithm with source-spectrum, detector and patient material modelling. Similarity between radiographs and matched DRRs was quantified using Pearson’s correlation and Czekanowski’s index, calculated on a per-image basis. Distributions of correlations and indexes were compared to test each of the hypotheses. Distribution differences were determined to be statistically significant when Wilcoxon’s signed rank test and the Kolmogorov-Smirnov two sample test returned p ≤ 0.05 for both tests. Main results. Intra-fraction radiographs were more similar to CBCT-DRRs than CT-DRRs for both metrics across all algorithms, with all p ≤ 0.007. Source-spectrum modelling improved radiograph-DRR similarity for both metrics, with all p < 10−6. OBI detector modelling and patient material modelling did not influence radiograph-DRR similarity for either metric. Significance. Generating DRRs from pre-treatment CBCT-DRRs is feasible, and incorporating CBCT-DRRs into markerless target-tracking methods may promote improved target-tracking accuracies. Incorporating source-spectrum modelling into a treatment planning system’s DRR algorithms may reinforce the safe treatment of cancer patients by aiding in patient alignment.

Treatment planning evaluation and experimental validation of the magnetic resonance-based intrafraction drift correction

Background and purposeMRI-guided online adaptive treatments can account for interfractional variations, however intrafraction motion reduces treatment accuracy. Intrafraction plan adaptation methods, such as the Intrafraction Drift Correction (IDC) or sub-fractionation, are needed. IDC uses real-time automatic monitoring of the tumor position to initiate plan adaptations by repositioning segments. IDC is a fast adaptation method that occurs only when necessary and this method could enable margin reduction. This research provides a treatment planning evaluation and experimental validation of the IDC. Materials and methodsAn in silico treatment planning evaluation was performed for 13 prostate patients mid-treatment without and with intrafraction plan adaptation (IDC and sub-fractionation). The adaptation methods were evaluated using dose volume histogram (DVH) metrics. To experimentally verify IDC a treatment was mimicked whereby a motion phantom containing an EBT3 film moved mid-treatment, followed by repositioning of segments. In addition, the delivered treatment was irradiated on a diode array phantom for plan quality assurance purposes. ResultsThe planning study showed benefits for using intrafraction adaptation methods relative to no adaptation, where the IDC and sub-fractionation showed consistently improved target coverage with median target coverages of 100.0%. The experimental results verified the IDC with high minimum gamma passing rates of 99.1% and small mean dose deviations of maximum 0.3%. ConclusionThe straightforward and fast IDC technique showed DVH metrics consistent with the sub-fractionation method using segment weight re-optimization for prostate patients. The dosimetric and geometric accuracy was shown for a full IDC workflow using film and diode array dosimetry.

146P Inter-fraction variation of internal target volume of lung tumour with 4D CT and 4D kV CBCT

146P Inter-fraction variation of internal target volume of lung tumour with 4D CT and 4D kV CBCT

Interfractional variation in whole-breast VMAT irradiation: a dosimetric study with complementary SGRT and CBCT patient setup

BackgroundThe dosimetric effect of setup uncertainty and tissue deformations in left-sided whole-breast irradiation with complementary surface-guided radiotherapy (SGRT) and cone-beam computed tomography (CBCT) setup was evaluated.MethodTreatment courses of 40.05 Gy prescribed dose in 15 fractions were simulated for 29 patients by calculating the dose on deformed CT images, that were based on daily CBCT images, and deforming and accumulating the dose onto the planning CT image. Variability in clinical target volume (CTV) position and shape was assessed as the 95% Hausdorff distance (HD95) between the planning CTV and deformed CTV structures. DVH metrics were evaluated between the planned and simulated cumulative dose distributions using two treatment techniques: tangential volumetric modulated arc therapy (tVMAT) and conventional 3D-conformal radiotherapy (3D-CRT).ResultsBased on the HD95 values, the variations in CTV shape and position were enclosed by the 5 mm CTV-PTV margin in 85% of treatment fractions using complementary CBCT and SGRT setup. A residual error of 8.6 mm was observed between the initial SGRT setup and CBCT setup. The median CTV V95% coverage was 98.1% (range 93.1–99.8%) with tVMAT and 98.2% (range 84.5–99.7%) with 3D-CRT techniques with CBCT setup. With the initial SGRT-only setup, the corresponding coverages were 96.3% (range 92.6–99.4%) and 96.6% (range 84.2–99.4%), respectively. However, a considerable bias in vertical residual error between initial SGRT setup and CBCT setup was observed. Clinically relevant changes between the planned and cumulative doses to organs-at-risk (OARs) were not observed.ConclusionsThe CTV-to-PTV margin should not be reduced below 5 mm even with daily CBCT setup. Both tVMAT and 3D-CRT techniques were robust in terms of dose coverage to the target and OARs. Based on the shifts between setup methods, CBCT setup is recommended as a complementary method with SGRT.

Intra- and inter-fractional variations of tumors with fiducial markers measured using respiratory-correlated computed tomography images for respiratory gated lung stereotactic body radiation therapy.

This study evaluated the intra- and inter-fractional variation of tumors with fiducial markers (FMs), relative to the tumor-FM distance, to establish how close an FM should be inserted for respiratory-gated stereotactic body radiation therapy (RG-SBRT). Forty-five lung tumors treated with RG-SBRT were enrolled. End-expiratory computed tomography (CT) (CTplan) and four-dimensional-CT (4D-CT) scans were obtained for planning. End-expiratory CT (CTfr) scanning was performed before each fraction. The FMs were divided into two groups based on the median tumor-FM distance in the CTplan (Dp). For the intra-fractional variation, the correlations between the corresponding tumor and FM intra-fractional motions, defined as the centroid coordinates of those in each 0-90% phase, with the 50% phase of 4D-CT as the origin, were calculated in the left-right, anterior-posterior, and superior-inferior directions. Furthermore, the maximum difference in the tumor-FM distance in each phase of 4D-CT scan, based on those in the 50% phase of 4D-CT scan (Dmax), was obtained. Inter-fractional variation was defined as the maximum distance between the tumors in CTplan and CTfr, when the CT scans were fused based on each FM or vertebra. The median Dp was 26.1mm. While FM intra-fractional motions were significantly and strongly correlated with the tumor intra-fractional motions in only anterior-posterior and superior-inferior directions for the Dp>26mm group, they were significantly and strongly correlated in all directions for the Dp ≤ 26mm group. In all directions, Dmax values of the Dp ≤ 26mm group were lower than those of the Dp>26mm group. The inter-fractional variations based on the Dp ≤ 26mm were smaller than those on the Dp>26mm and on the vertebra in all directions. Regarding intra- and inter-fractional variation, FMs for Dp ≤ 26mm can increase the accuracy for RG-SBRT.

The Role of Proton Therapy for Prostate Cancer in the Setting of Hip Prosthesis.

Given that the current standard of proton therapy (PT) for prostate cancer is through bilateral beams, this modality is typically avoided when it comes to treatment of patients with hip prosthesis. The purpose of this study was to evaluate whether novel PT methods, i.e., anterior proton beams and proton arc therapy (PArc), could be feasible options to treat this patient subpopulation. We evaluate PT methods in the context of dosimetry and robustness and compare with standard of practice volumetric modulated arc therapy (VMAT) to explore any potential benefits. Two PT and one VMAT treatment plans were retrospectively created for 10 patients who participated in a clinical trial with a weekly repeat CT (rCT) imaging component. All plans were robustly optimized and featured: (1) combination anterior oblique and lateral proton beams (AoL), (2) PArc, and (3) VMAT. All patients had hydrogel spacers in place, which enabled safe application of anterior proton beams. The planned dose was 70 Gy (RBE) to the entire prostate gland and 50 Gy (RBE) to the proximal seminal vesicles in 28 fractions. Along with plan dose-volume metrics, robustness to setup and interfractional variations were evaluated using the weekly rCT images. The linear energy transfer (LET)-weighted dose was evaluated for PArc plans to ensure urethra sparing given the typical high-LET region at the end of range. Both PT methods were dosimetrically feasible and provided reduction of some key OAR metrics compared to VMAT except for penile bulb, while providing equally good target coverage. Significant differences in median rectum V35 (22-25%), penile bulb Dmean (5 Gy), rectum V61 (2%), right femoral head Dmean (5 Gy), and bladder V39 (4%) were found between PT and VMAT. All plans were equally robust to variations. LET-weighted dose in urethra was equivalent to the physical dose for PArc plans and hence no added urethral toxicity was expected. PT for treatment of prostate cancer patients with hip prosthesis is feasible and equivalent or potentially superior to VMAT in quality in some cases. The choice of radiotherapy regimen can be personalized based on patient characteristics to achieve the best treatment outcome.

Prospects for online adaptive radiation therapy (ART) for head and neck cancer

BackgroundThe aim of the present study is to examine the impact of kV-CBCT-based online adaptive radiation therapy (ART) on dosimetric parameters in comparison to image-guided-radiotherapy (IGRT) in consecutive patients with tumors in the head and neck region from a prospective registry.MethodsThe study comprises all consecutive patients with tumors in the head and neck area who were treated with kV-CBCT-based online ART or IGRT-modus at the linear-accelerator ETHOS™. As a measure of effectiveness, the equivalent-uniform-dose was calculated for the CTV (EUDCTV) and organs-at-risk (EUDOAR) and normalized to the prescribed dose. As an important determinant for the need of ART the interfractional shifts of anatomic landmarks related to the tongue were analyzed and compared to the intrafractional shifts. The latter determine the performance of the adapted dose distribution on the verification CBCT2 postadaptation.ResultsAltogether 59 consecutive patients with tumors in the head-and-neck-area were treated from 01.12.2021 to 31.01.2023. Ten of all 59 patients (10/59; 16.9%) received at least one phase within a treatment course with ART. Of 46 fractions in the adaptive mode, irradiation was conducted in 65.2% of fractions with the adaptive-plan, the scheduled-plan in the remaining. The dispersion of the distributions of EUDCTV-values from the 46 dose fractions differed significantly between the scheduled and adaptive plans (Ansari-Bradley-Test, p = 0.0158). Thus, the 2.5th percentile of the EUDCTV-values by the adaptive plans amounted 97.1% (95% CI 96.6–99.5%) and by the scheduled plans 78.1% (95% CI 61.8–88.7%). While the EUDCTV for the accumulated dose distributions stayed above 95% at PTV-margins of ≥ 3 mm for all 8 analyzed treatment phases the scheduled plans did for margins ≥ 5 mm. The intrafractional anatomic shifts of all 8 measured anatomic landmarks were smaller than the interfractional with overall median values of 8.5 mm and 5.5 mm (p < 0.0001 for five and p < 0.05 for all parameters, pairwise comparisons, signed-rank-test). The EUDOAR-values for the larynx and the parotid gland were significantly lower for the adaptive compared with the scheduled plans (Wilcoxon-test, p < 0.001).ConclusionsThe mobile tongue and tongue base showed considerable interfractional variations. While PTV-margins of 5 mm were sufficient for IGRT, ART showed the potential of decreasing PTV-margins and spare dose to the organs-at-risk.

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

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

Is noncoplanar plan more robust to inter-fractional variations than coplanar plan in treating bilateral HN tumors with pencil-beam scanning proton beams?

Noncoplanar plans (NCPs) are commonly used for proton treatment of bilateral head and neck (HN) malignancies. NCP requires additional verification setup imaging between beams to correct residual errors of robotic couch motion, which increases imaging dose and total treatment time. This study compared the quality and robustness of NCPs with those of coplanar plans (CPs). Under an IRB-approved study, CPs were created retrospectively for 10 bilateral HN patients previously treated with NCPs maintaining identical beam geometry of the original plan but excluding couch rotations. Plan robustness to the inter-fractional variation (IV) of both plans was evaluated through the Dose Volume Histograms (DVH) of weekly quality assurance CT (QACT) sets (39 total). In addition, delivery efficiency for both plans was compared using total treatment time (TTT) and beam-on time (BOT). No significant differences in plan quality were observed in terms of clinical target volume (CTV) coverage (D95) or organ-at-risk (OAR) doses (p>0.4 for all CTVs and OARs). No significant advantage of NCPs in the robustness to IV was found over CP, either. Changes in D95 of QA plans showed a linear correlation (slope=1.006, R2 >0.99) between NCP and CP for three CTV data points (CTV1, CTV2, and CTV3) in each QA plan (117 data points for 39 QA plans). NCPs showed significantly higher beam delivery time than CPs for TTT (539±50vs. 897±142s; p<0.001); however, no significant differences were observed for BOT. NCPs are not more robust to IV than CPs when treating bilateral HN tumors with pencil-beam scanning proton beams. CPs showed plan quality and robustness similar to NCPs while reduced treatment time (∼6min). This suggests that CPs may be a more efficient planning technique for bilateral HN cancer proton therapy.

CT-based online adaptive radiotherapy improves target coverage and organ at risk (OAR) avoidance in stereotactic body radiation therapy (SBRT) for prostate cancer

IntroductionStereotactic body radiation therapy (SBRT) is an emerging treatment modality for clinically localized prostate cancer (PCa). Online daily adaptive radiotherapy (ART) could potentially improve the therapeutic ratio of prostate SBRT by accounting for inter-fraction variation in target and OAR volumes. To our knowledge, no group has evaluated the clinical utility of a novel AI-augmented CT-based ART system for prostate SBRT. In this study we hypothesized that adaptive prostate SBRT plans would result in improved target coverage and lower dose to OARs in comparison to unadapted treatment plans. MethodsSeven patients with favorable intermediate to oligometastatic PCa treated with 5-fx prostate adaptive SBRT were retrospectively reviewed. Patients were treated with 3625 cGy to the prostate and seminal vesicles. 6 patients additionally received 2500 cGy to the pelvic nodes, 5 patients underwent a boost to 4000 cGy to the prostate. For each fraction, a CBCT was acquired and OARs (rectum, bladder, bowel, sigmoid, femurs) were segmented/deformed using AI. CTVs were rigidly registered. Volumes were adjusted manually and PTV expansions added. Adaptive treatment plans were developed based on the contoured targets and OARs and dose to these volumes for the adapted vs. initial plans were compared for each fraction. V100 and the D0.03 cc between scheduled and adapted treatment plans were compared using a Student’s t-test, with significance threshold of P < 0.05. ResultsSeven patients completed 35 Fx’s of adaptive RT. Daily adaptation resulted in a statistically significant mean improvement in PTV V100 for all targets: [21.4 % ± 4.3 % for PTV 4000 (p < 0.0001); 8.7 % ± 1.1 % for PTV 3625 (p < 0.0001); and 11.5 % ± 3.1 % for PTV 2500 (p = 0.0013)]. Mean rectal D0.03 was significantly reduced by 38.8 cGy ± 5.95 cGy (p < 0.0001) per fraction (194 cGy/5 fractions) compared to the initial plans. There was a modest increase in bladder dose of 10.9 cGy ± 4.93 cGy per fraction (p = 0.0424) for the adaptive plans. The adaptive plans met bladder constraints for every fraction. There were no statistically significant differences between sigmoid or bowel dose for adapted vs. initial plans. No patients experienced acute CTCAE grade ≥ 3 GI/GU adverse events (median F/U 9.5 months). All statistically significant differences were maintained in the presence and absence of rectal hydrogel spacer (p < 0.05). ConclusionsCT-based online adaptive SBRT resulted in statistically significant and clinically meaningful improvements in PTV coverage and D0.03 cc dose to the rectum. A trial evaluating CT adaptive whole-pelvis prostate SBRT is underway.

Clinical Implementation of “Plan of the Day” Strategy in Definitive Radiation Therapy of Cervical Cancer: Online Adaptation to Address the Challenge of Organ Filling Reproducibility

Background: Definitive pelvic intensity-modulated radiotherapy (IMRT) in cervical cancer is susceptible to geographic miss due to daily positional and volumetric variations in target and organs at risk. Hence, despite evidence of reduced acute and late treatment-related toxicities, implementation of image-guided IMRT (IG-IMRT) with a reasonable safety margin to encompass organ motion is challenging. Materials and Methods: In this prospective, non-randomized phase II study, patients with cervical cancer FIGO (2009) stage IB2-IIIB between the ages of 18 and 65 years were treated with definitive pelvic CT-RT with a pre-specified organ (bladder and rectum) filling protocol. Reproducibility of organ filling was assessed along with the implementation of daily comprehensive adaptive IGRT, with a library of 3 IMRT (VMAT) plans with incremental expansions of CTV to PTV (Primary) margins (small 0.7 cm, adequate 1 cm and large 1.5 cm) and a backup motion robust 3DCRT plan; the appropriate plan is chosen based on pre-treatment CBCT (‘Plan of the Day’ approach). Results: Fifty patients with a median age of 49 years (IQR 45-56 years), received definitive RT (45-46Gy in 23-25 fractions to pelvis; with simultaneous integrated boost to gross nodes in 15 patients) with the said IGRT protocol. In the analysis of 1171 CBCT images (in 1184 treatment sessions), the mean planning CT and CBCT bladder volumes were 417 ccs and 373 ccs respectively. Significant inter-fractional variation in bladder volume was noted with a mean absolute dispersion of 29.5% with respect to planning CT; significant influential random factors were post-chemotherapy sessions (p=<0.001), pre-CBCT protocol duration (p= 0.001), grades of CINV (p=0.001). Significantly higher variation in bladder filling noted in patients with higher age (p=0.014) and larger planning CT bladder volume (p=<0.001). Time trend analysis of fraction-wise bladder volume revealed an absolute systemic reduction of 16.3% in bladder volume means from 1st to 5th week. Variation in rectal diameter was much less pronounced, with 19.2% mean dispersion, without any significant factors affecting it.While in 19% and 2% of sessions ‘Large’ IMRT PTV and ‘3DCRT’ were necessary to cover the primary target respectively, reduction in treated volume was possible in 43% of sessions with ‘Small’ PTV selection instead of standard ‘Adequate’ PTV (36% sessions). ‘Plan of the day’ selection had a moderate to strong correlation with non-absolute dispersion of bladder filling (Spearman's R= 0.4; p= 0.001) and a weak (but significant) correlation with grades of acute toxicities. The planned protocol was well tolerated with no radiation-induced local grade III toxicity. Conclusion: Inter-fractional variation in organ filling (especially bladder) is inevitable despite fixed pre-treatment protocol in definitive settings (intact cervix). Despite the logistical challenges; adaptive IGRT in form of ‘plan of the day’ based on incremental CTV-to-PTV margins is a relatively simple and feasible strategy to minimise geometric uncertainties in radical IG-IMRT of cervical cancer.

Intra- and inter-fraction breath-hold variations and margins for radiotherapy of abdominal targets

Radiotherapy in expiration breath-hold (EBH) has the potential to reduce treatment volumes of abdominal targets compared to an internal target volume concept in free-breathing. The reproducibility of EBH and required safety margins were investigated to quantify this volumetric benefit. Pre- and post-treatment diaphragm position difference and the positioning variability were determined on computed tomography. Systematic and random errors for EBH position reproducibility and positioning variability were calculated, resulting in margins of 7 to 12 mm depending on the prescription isodose and fractionation. A reduced volume was shown for EBH for lesions with superior-inferior breathing motion above 4 to 8 mm.

Experimental validation of multi-fraction online adaptations in magnetic resonance guided radiotherapy

Background and purposeRadiotherapy plan verification is generally performed on the reference plan based on the pre-treatment anatomy. However, the introduction of online adaptive treatments demands a new approach, as plans are created daily on different anatomies. The aim of this study was to experimentally validate the accuracy of total doses of multi-fraction plan adaptations in magnetic resonance imaging guided radiotherapy in a phantom study, isolated from the uncertainty of deformable image registration. Materials and methodsWe experimentally verified the total dose, measured on external beam therapy 3 (EBT3) film, using a treatment with five online adapted fractions. Three series of experiments were performed, each focusing on a category of inter-fractional variation; translations, rotations and body modifications. Variations were introduced during each fraction and adapted plans were generated and irradiated. Single fraction doses and total doses over five online adapted fractions were investigated. ResultsThe online adapted measurements and calculations showed a good agreement for single fractions and multi-fraction treatments for the dose profiles, gamma passing rates, dose deviations and distances to agreement. The gamma passing rate using a 2%/2 mm criterion ranged from 99.2% to 99.5% for a threshold dose of 10% of the maximum dose (Dmax) and from 96.2% to 100% for a threshold dose of 90% of Dmax, for the total translations, rotations and body modifications. ConclusionsThe total doses of multi-fraction treatments showed similar accuracies compared to single fraction treatments, indicating an accurate dosimetric outcome of a multi-fraction treatment in adaptive magnetic resonance imaging guided radiotherapy.