Characterization of Ethos therapy systems for adaptive radiation therapy: A multi-machine comparison.

PURPOSE: The recently released Ethos therapy system (Varian Medical Systems) allows for online CBCT-guided adaptive radiation therapy (RT). The clinical introduction of multiple systems requires machine characterization and machine variation quantification to allow patient interchangeability between systems. Despite several clinical introductions, limited vendor-independent information on machine performance is available. Our aim was to determine the relevant dosimetric and mechanical characteristics of individual machines and to quantify machine variations. METHODS: Six Ethos treatment machines, equipped with a 6-MV FFF beam including dual-layer MLC and kV-CBCT system, were recently introduced clinically after extensive machine characterization and pre-configured beam model verification. Point doses and profiles were measured and compared to vendor-provided reference data and dose calculations. Also, dose calculations were verified based on point measurements for non-standard fields and dose distributions for optimized treatment plans. Agreements between dose profiles (dose distributions) were quantified using 1D (3D) γ-analysis. Additionally, we quantified leaf transmission, dosimetric leaf gap (DLG) and couch attenuation, determined isocenter accuracy and kV-MV isocenter coincidence and verified the kV-CBCT system. Machine variations were quantified for all dosimetric and mechanical characteristics. RESULTS: For all machines, distinct agreements were found between measurements and vendor-provided reference data as well as measurements and dose calculations. Mean γ1%/1mm values for all profiles were below 0.30. All profiles, point measurements and dose distributions matched well among the six machines. Minimal machine variations were found in terms of DLG (0.05 mm), leaf transmission (0.001%), isocenter accuracy (0.08 mm), kV-MV isocenter coincidence (0.15 mm), couch attenuation (0.69%), and CBCT imaging dose (0.29 mGy). CONCLUSIONS: This study demonstrates excellent agreement between individual Ethos therapy systems and vendor-provided reference data as well as a pre-configured beam model. Furthermore, our results show good consistency among all machines and provide valuable insights on relevant machine characteristics. The systematically obtained results provide benchmark data for future clinical introduction of Ethos therapy systems.

Evaluation of plan quality in radiotherapy planning with an MR-linac.

BACKGROUND & PURPOSE: Clinical introduction of magnetic resonance (MR)-guided radiotherapy involves treatment planning while taking into account machine-specific characteristics. Our aim was to investigate the feasibility of high-quality MR-linac treatment planning for an MR-linac and to benchmark MR-linac plan quality (IMRT) against current clinical practice (VMAT). MATERIALS & METHODS: Data of eight rectal and eight prostate cancer patients, who received radiotherapy on a conventional CBCT-integrated linac, were selected. Clinically acquired CTs and associated delineations of target volumes and organs-at-risk (OARs) were used for MR-linac treatment planning in Monaco. To investigate treatment planning software bias 'quasi MR-linac plans' were generated in Pinnacle3 by mimicking MR-linac specific beam characteristics. MR-linac, quasi MR-linac, and clinical plans were compared and differences in target and OAR doses assessed. Differences in plan complexity were determined by the number of segments and monitor units. RESULTS: Compared to clinical plans, MR-linac plans showed a statistically significant decrease in plan homogeneity, an increase in PTV Dmean (prostate: 0.6 Gy; rectum: 0.8 Gy) and D1% (prostate: 1.9 Gy; rectum: 2.0 Gy), and increases in OAR dose. Quasi MR-linac plans were comparable to MR-linac plans with respect to OAR dose and plan homogeneity. For rectal cancer an increase was seen in PTV Dmean (0.12 Gy) and D1% (0.5 Gy) compared to regular MR-linac plans. All created plans were clinically equivalent to current clinical practice. CONCLUSIONS: This study demonstrates the feasibility of creating high-quality MR-linac treatment plans. The results supported the clinical introduction of an MR-linac.

Target tailoring and proton beam therapy to reduce small bowel dose in cervical cancer radiotherapy : A comparison of benefits.

PURPOSE: The aim of the study was to investigate the potential clinical benefit from both target tailoring by excluding the tumour-free proximal part of the uterus during image-guided adaptive radiotherapy (IGART) and improved dose conformity based on intensity-modulated proton therapy (IMPT). METHODS: The study included planning CTs from 11 previously treated patients with cervical cancer with a >4-cm tumour-free part of the proximal uterus on diagnostic magnetic resonance imaging (MRI). IGART and robustly optimised IMPT plans were generated for both conventional target volumes and for MRI-based target tailoring (where the non-invaded proximal part of the uterus was excluded), yielding four treatment plans per patient. For each plan, the V15Gy, V30Gy, V45Gy and Dmean for bladder, sigmoid, rectum and bowel bag were compared, and the normal tissue complication probability (NTCP) for ≥grade 2 acute small bowel toxicity was calculated. RESULTS: Both IMPT and MRI-based target tailoring resulted in significant reductions in V15Gy, V30Gy, V45Gy and Dmean for bladder and small bowel. IMPT reduced the NTCP for small bowel toxicity from 25% to 18%; this was further reduced to 9% when combined with MRI-based target tailoring. In four of the 11 patients (36%), NTCP reductions of >10% were estimated by IMPT, and in six of the 11 patients (55%) when combined with MRI-based target tailoring. This >10% NTCP reduction was expected if the V45Gy for bowel bag was >275 cm3 and >200 cm3, respectively, during standard IGART alone. CONCLUSIONS: In patients with cervical cancer, both proton therapy and MRI-based target tailoring lead to a significant reduction in the dose to surrounding organs at risk and small bowel toxicity.

Dosimetric advantages of a clinical daily adaptive plan selection strategy compared with a non-adaptive strategy in cervical cancer radiation therapy.

BACKGROUND: Radiation therapy (RT) using a daily plan selection adaptive strategy can be applied to account for interfraction organ motion while limiting organ at risk dose. The aim of this study was to quantify the dosimetric consequences of daily plan selection compared with non-adaptive RT in cervical cancer. MATERIAL AND METHODS: Ten consecutive patients who received pelvic irradiation, planning CTs (full and empty bladder), weekly post-fraction CTs and pre-fraction CBCTs were included. Non-adaptive plans were generated based on the PTV defined using the full bladder planning CT. For the adaptive strategy, multiple PTVs were created based on both planning CTs by ITVs of the primary CTVs (i.e., GTV, cervix, corpus-uterus and upper part of the vagina) and corresponding library plans were generated. Daily CBCTs were rigidly aligned to the full bladder planning CT for plan selection. For daily plan recalculation, selected CTs based on initial similarity were deformably registered to CBCTs. Differences in daily target coverage (D98% > 95%) and in V0.5Gy, V1.5Gy, V2Gy, D50% and D2% for rectum, bladder and bowel were assessed. RESULTS: Non-adaptive RT showed inadequate primary CTV coverage in 17% of the daily fractions. Plan selection compensated for anatomical changes and improved primary CTV coverage significantly (p < 0.01) to 98%. Compared with non-adaptive RT, plan selection decreased the fraction dose to rectum and bowel indicated by significant (p < 0.01) improvements for daily V0.5Gy, V1.5Gy, V2Gy, D50% and D2%. However, daily plan selection significantly increased the bladder V1.5Gy, V2Gy, D50% and D2%. CONCLUSIONS: In cervical cancer RT, a non-adaptive strategy led to inadequate target coverage for individual patients. Daily plan selection corrected for day-to-day anatomical variations and resulted in adequate target coverage in all fractions. The dose to bowel and rectum was decreased significantly when applying adaptive RT.

Dose coverage calculation using a statistical shape model-applied to cervical cancer radiotherapy.

A comprehensive methodology for treatment simulation and evaluation of dose coverage probabilities is presented where a population based statistical shape model (SSM) provide samples of fraction specific patient geometry deformations. The learning data consists of vector fields from deformable image registration of repeated imaging giving intra-patient deformations which are mapped to an average patient serving as a common frame of reference. The SSM is created by extracting the most dominating eigenmodes through principal component analysis of the deformations from all patients. The sampling of a deformation is thus reduced to sampling weights for enough of the most dominating eigenmodes that describe the deformations. For the cervical cancer patient datasets in this work, we found seven eigenmodes to be sufficient to capture 90% of the variance in the deformations of the, and only three eigenmodes for stability in the simulated dose coverage probabilities. The normality assumption of the eigenmode weights was tested and found relevant for the 20 most dominating eigenmodes except for the first. Individualization of the SSM is demonstrated to be improved using two deformation samples from a new patient. The probabilistic evaluation provided additional information about the trade-offs compared to the conventional single dataset treatment planning.

Dosimetric advantages of proton therapy compared with photon therapy using an adaptive strategy in cervical cancer.

Background Image-guided adaptive proton therapy (IGAPT) can potentially be applied to take into account interfraction motion while limiting organ at risk (OAR) dose in cervical cancer radiation therapy (RT). In this study, the potential dosimetric advantages of IGAPT compared with photon-based image-guided adaptive RT (IGART) were investigated. Material and methods For 13 cervical cancer patients, full and empty bladder planning computed tomography (CT) images and weekly CTs were acquired. Based on both primary clinical target volumes (pCTVs) [i.e. gross tumor volume (GTV), cervix, corpus-uterus and upper part of the vagina] on planning CTs, the pretreatment observed full range primary internal target volume (pITV) was interpolated to derive pITV subranges. Given corresponding ITVs (i.e. pITVs including lymph nodes), patient-specific photon and proton plan libraries were generated. Using all weekly CTs, IGART and IGAPT treatments were simulated by selecting library plans and recalculating the dose. For each recalculated IGART and IGAPT fraction, CTV (i.e. pCTV including lymph nodes) coverage was assessed and differences in fractionated substitutes of dose-volume histogram (DVH) parameters (V15Gy, V30Gy, V45Gy, Dmean, D2cc) for bladder, bowel and rectum were tested for significance (Wilcoxon signed-rank test). Also, differences in toxicity-related DVH parameters (rectum V30Gy, bowel V45Gy) were approximated based on accumulated dose distributions. Results In 92% (96%) of all recalculated IGAPT (IGART) fractions adequate CTV coverage (V95% >98%) was obtained. All dose parameters for bladder, bowel and rectum, except the fractionated substitute for rectum V45Gy, were improved using IGAPT. Also, IGAPT reduced the mean dose to bowel, bladder and rectum significantly (p < 0.01). In addition, an average decrease of rectum V30Gy and bowel V45Gy indicated reductions in toxicity probabilities when using IGAPT. Conclusion This study demonstrates the feasibility of IGAPT in cervical cancer using a plan-library based plan-of-the-day approach. Compared to photon-based IGART, IGAPT maintains target coverage while significant dose reductions for the bladder, bowel and rectum can be achieved.

Quantification of delineation errors of the gross tumor volume on magnetic resonance imaging in uterine cervical cancer using pathology data and deformation correction.

BACKGROUND: To safely optimize target volumes using magnetic resonance imaging (MRI) for uterine cervical cancer radiation therapy, MRI findings need to be validated. The aim of this study was to correlate pre-operatively acquired MRI and surgical specimen imaging for uterine cervical cancer patients using deformable image registration and quantify gross tumor volume (GTV) delineation discrepancies. MATERIAL AND METHODS: For 16 retrospectively selected early-stage uterine cervical cancer patients, the cervix-uterus structure, uterine cavity and the GTV were delineated on 2D pathology photos after macroscopic intersection and corresponding pre-operatively acquired T2-weighted 2D sagittal MR images. Segmentations of pathology photos and MR images were simultaneously registered using a three-step multi-image registration strategy. The registration outcome was evaluated by the Dice similarity coefficient (DSC) and the surface distance error (SDE). In addition, GTV expansions within the cervix-uterus structure needed to obtain 95% GTV coverage were determined. RESULTS: After three-step multi-image registration, the median DSC and median SDE were 0.98 and 0.4 mm (cervix-uterus) and 0.90 and 0.4 mm (uterine cavity), respectively. The average SDE around the GTV was 0.7 mm (range, 0.1 mm - 2.6 mm). An underestimation of MRI-based GTV delineations was found when no margin was applied, indicated by a mean GTV coverage of 61%. To obtain 95% GTV coverage for 90% of the patients, a minimum 12.0 mm margin around MRI-based GTVs was needed. CONCLUSION: The presented three-step multi-image registration strategy was suitable and accurate to correlate MRI and pathology data for uterine cervical cancer patients. To cover the pathology-based GTV, a margin of at least 12.0 mm around GTV delineations on T2-weighted MRI is needed.

Craniocaudal tumour extension in uterine cervical cancer on MRI compared to histopathology.

PURPOSE: To assess the reliability of magnetic resonance imaging (MRI) for evaluation of craniocaudal tumour extension by comparing the craniocaudal tumour extension on the pre-operative MRI and post-operative hysterectomy specimen in patients with early stage uterine cervical cancer. MATERIALS AND METHODS: After approval of the institutional review board was acquired, pre-operative MRI and hysterectomy specimen of 21 women with early stage cervical cancer were re-evaluated. The craniocaudal extension on MRI was measured separately by two experienced radiologists and compared with corresponding measurements from the hysterectomy specimen, which were re-evaluated by an experienced pathologist. RESULTS: Median craniocaudal extension of uterine cervical cancer on MRI was slightly smaller compared to histopathology (2.1 cm vs. 2.5 cm). The median underestimation was 0.4 cm (range -0.6 cm to 2.2 cm, mean 0.4 cm, standard deviation (SD) ±0.7 cm); Pearson's correlation was 0.83 (p < 0.001). In two patients (9%) MRI underestimated tumour craniocaudal extension by more than 1.8 cm. CONCLUSION: MRI represents the histopathological craniocaudal tumour extension in the majority of patients with early stage uterine cervical cancer, but with a systematic small underestimation of the real craniocaudal tumour extension.