Adaptive radiation therapy strategies in the treatment of prostate cancer patients using hypofractionated VMAT.

PURPOSE: To perform a comprehensive evaluation of eight adaptive radiation therapy strategies in the treatment of prostate cancer patients who underwent hypofractionated volumetric modulated arc therapy (VMAT) treatment. MATERIAL AND METHODS: The retrospective study included 20 prostate cancer patients treated with 40 Gy total dose over five fractions (8 Gy/fraction) using VMAT. Daily cone beam computed tomography images were acquired before the delivery of every fraction and then, with the application of deformable image registration used for the estimation of daily dose, contouring and plan re-optimization. Dosimetric benefits of the various ART strategies were quantified by the comparison of dose and dose-volume metrics derived from treatment planning objectives for original treatment plan and adapted plans with the consideration of target volumes (PTV and CTV) as well as critical structures (bladder, rectum, left, and right femoral heads). RESULTS: Percentage difference (ΔD) between planning objectives and delivered dose in the D99%  > 4000cGy (CTV) metric was -3.9% for the non-ART plan and 2.1% to 4.1% for ART plans. For D99%  > 3800cGy and Dmax  < 4280cGy (PTV), ΔD was -11.2% and -6.5% for the non-ART plan as well as -3.9% to -1.6% and -0.2% to 1.8% for ART plans, respectively. For D15%  < 3200 cGy and D20%  < 2800 cGy (bladder), ΔD was -62.4% and -68.8% for the non-ART plan as well as -60.0% to -57.4% and -67.0% to -64.0% for ART plans. For D15%  < 3200 cGy and D20%  < 2800 cGy (rectum), ΔD was -11.4% and -8.15% for non-ART plan as well as -14.9% to -9.0% and -11.8% to -5.1% for ART plans. CONCLUSIONS: Daily on-line adaptation approaches were the most advantageous, although strategies adapting every other fraction were also impactful while reducing relative workload as well. Offline treatment adaptations were shown to be less beneficial due to increased dose delivered to bladder and rectum compared toother ART strategies.

Impact of daily plan adaptation on accumulated doses in ultra-hypofractionated magnetic resonance-guided radiation therapy of prostate cancer.

Background and purpose: Ultra-hypofractionated online adaptive magnetic resonance-guided radiotherapy (MRgRT) is promising for prostate cancer. However, the impact of online adaptation on target coverage and organ-at-risk (OAR) sparing at the level of accumulated dose has not yet been reported. Using deformable image registration (DIR)-based accumulation, we compared the delivered adapted dose with the simulated non-adapted dose. Materials and methods: Twenty-three prostate cancer patients treated at two clinics with 0.35 T magnetic resonance-guided linear accelerator (MR-linac) following the same treatment protocol (5 × 7.5 Gy with urethral sparing and daily adaptation) were included. The fraction MR images were deformably registered to the planning MR image. Both non-adapted and adapted fraction doses were accumulated with the corresponding vector fields. Two DIR approaches were implemented. PTV* (planning target volume minus urethra+2mm) D95%, CTV* (clinical target volume minus urethra) D98%, and OARs (urethra+2mm, bladder, and rectum) D0.2cc, were evaluated. Statistical significance was inferred from a two-tailed Wilcoxon signed-rank test (p < 0.05). Results: Normalized to the baseline, the accumulated PTV* D95% increased significantly by 2.7 % ([1.5, 4.3]%) through adaptation, and the CTV* D98% by 1.2 % ([0.1, 1.7]%). For the OARs after adaptation, accumulated bladder D0.2cc decreased by 0.4 % ([-1.2, 0.4]%), urethra+2mmD0.2cc by 0.8 % ([-1.6, -0.1]%), while rectum D0.2cc increased by 2.6 % ([1.2, 4.9]%). For all patients, rectum D0.2cc was still below the clinical constraint. Results of both DIR approaches differed on average by less than 0.2 %. Conclusions: Online adaptation in MRgRT improved target coverage and OARs sparing at the level of accumulated dose.

Analysis of online plan adaptation for 1.5T magnetic resonance-guided stereotactic body radiotherapy (MRgSBRT) of prostate cancer.

PURPOSE: To analyze and characterize the online plan adaptation of 1.5T magnetic resonance-guided stereotactic body radiotherapy (MRgSBRT) of prostate cancer (PC). METHODS: PC patients (n = 107) who received adaptive 1.5 Tesla MRgSBRT were included. Online plan adaptation was implemented by either the adapt-to-position (ATP) or adapt-to-shape (ATS) methods. Patients were assigned to the ATS group if they underwent ≥ 1 ATS fraction (n = 51); the remainder were assigned to the ATP group (n = 56). The online plan adaptation records of 535 (107 × 5) fractions were retrospectively reviewed. Rationales for ATS decision-making were determined and analyzed using predefined criteria. Statistics of ATS fractions were summarized. Associations of patient characteristics and clinical factors with ATS utilization were investigated. RESULTS: There were 87 (16.3%) ATS fractions and 448 ATP fractions (83.7%). The numbers of ATS adoptions in fractions 1-5 were 29 (29/107, 27.1%), 18 (16.8%), 15 (14.0%), 16 (15.0%), and 9 (8.4%), respectively, with significant differences in adoption frequency between fractions (p = 0.007). Other baseline patient characteristics and clinical factors were not significantly associated with ATS classification (all p > 0.05). Underlying criteria for the determination of ATS implementation comprised anatomical changes (77 fractions in 50 patients) and discrete multiple targets (15 fractions in 3 patients). No ATS utilization was determined using dosimetric or online quality assurance criteria. CONCLUSIONS: This study contributes to facilitating the establishment of a standardized protocol for online MR-guided adaptive radiotherapy in PC.

Benchmarking daily adaptation using fully automated radiotherapy treatment plan optimization for rectal cancer.

Background/purpose: In daily plan adaptation the radiotherapy treatment plan is adjusted just prior to delivery. A simple approach is taking the planning objectives of the reference plan and directly applying these in re-optimization. Here we present a tested method to verify whether daily adaptation without tweaking of the objectives can maintain the plan quality throughout treatment. Materials/methods: For fifteen rectal cancer patients, automated treatment planning was used to generate plans mimicking manual reference plans on the planning scans. For 74 fraction scans (4-5 per patient) an automated plan and a daily adapted plan were generated, where the latter re-optimizes the reference plan objectives without any tweaking. To evaluate the robustness of the daily adaptation, the adapted plans were compared to the autoplanning plans. Results: Median differences between the autoplanning plans on the planning scans and the reference plans were between -1 and 0.2 Gy. The largest interquartile range (1 Gy) was seen for the Lumbar Skin D2%. For the daily scans the PTV D2% and D98% differences between autoplanning and adapted plans were within ± 0.7 Gy, with mean differences within ± 0.3 Gy. Positive differences indicate higher values were obtained using autoplanning. For the Bowelarea + Bladder and the Lumbar Skin the D2% and Dmean differences were all within ± 2.6 Gy, with mean differences between -0.9 and 0.1 Gy. Conclusion: Automated treatment planning can be used to benchmark daily adaptation techniques. The investigated adaptation workflow can robustly perform high quality adaptations without daily adjusting of the patient-specific planning objectives for rectal cancer radiotherapy.

Magnetic Resonance-guided Stereotactic Radiotherapy for Localized Prostate Cancer: Final Results on Patient-reported Outcomes of a Prospective Phase 2 Study.

BACKGROUND: The recent introduction of magnetic resonance-guided radiation therapy (MRgRT) has allowed improved treatment planning and delivery of stereotactic body radiotherapy (SBRT) in prostate cancer (PC). The health-related quality of life (HRQoL) outcomes using this novel approach are important in shared decision making for patients. OBJECTIVE: To report HRQoL using both patient- and clinician-reported outcomes at 1 yr following stereotactic MRgRT for patients with localized PC. DESIGN, SETTING, AND PARTICIPANTS: A prospective phase 2 trial included 101 patients with localized PC. INTERVENTION: All patients received 36.25Gy in five fractions of MRgRT delivered within 2 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: HRQoL was prospectively assessed at baseline, at the last fraction, at 6 wk, and at 3, 6, 9, and 12 mo after treatment, by patient-reported outcome measures using European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-PR25 questionnaires, and International Prostate Symptom Score. At the same time points, clinicians reported on symptomatic adverse events (AEs). Effect sizes for changes in HRQoL were calculated with repeated measures analysis of variance. RESULTS AND LIMITATIONS: Availability of HRQoL data exceeded 95% at all study time points. From both questionnaires and the recorded AEs, the largest treatment effects on urinary and bowel symptoms were recorded in the first 6 wk of follow-up. Thereafter, all symptoms decreased and returned to baseline values at 12 mo. No grade ≥3 toxicity was reported. No patient reported any relevant limitation due to urinary symptoms, and only 2.2% of patients reported a relevant impact on daily activities due to bowel problems at 1 yr. The majority of patients had intermediate- or high-risk PC for which androgen deprivation therapy (83.2%) was prescribed, thereby precluding study of MRgRT on sexual function. Longer follow-up is awaited in order to evaluate the oncological outcome. CONCLUSIONS: Delivery of MRgRT for SBRT resulted in low toxicity at 1 yr. PATIENT SUMMARY: All patients completed magnetic resonance-guided radiation therapy, which was well tolerated with only transient early urinary and bowel symptoms, which resolved 1 yr after treatment, as confirmed by patient-reported outcome measures.

Target coverage and dose criteria based evaluation of the first clinical 1.5T MR-linac SBRT treatments of lymph node oligometastases compared with conventional CBCT-linac treatment.

BACKGROUND AND PURPOSE: Patients were treated at our institute for single and multiple lymph node oligometastases on the 1.5T MR-linac since August 2018. The superior soft-tissue contrast and additional software features of the MR-linac compared to CBCT-linacs allow for online adaptive treatment planning. The purpose of this study was to perform a target coverage and dose criteria based evaluation of the clinically delivered online adaptive radiotherapy treatment compared with conventional CBCT-linac treatment. MATERIALS AND METHODS: Patient data was used from 14 patients with single lymph node oligometastases and 6 patients with multiple (2-3) metastases. All patients were treated on the 1.5T MR-linac with a prescribed dose of 5 × 7 Gy to 95% of the PTV and a CBCT-linac plan was created for each patient. The difference in target coverage between these plans was compared and plans were evaluated based on dose criteria for each fraction after calculating the CBCT-plan on the daily anatomy. The GTV coverage was evaluated based on the online planning and the post-delivery MRI. RESULTS: For both single and multiple lymph node oligometastases the GTV V35Gy had a median value of 100% for both the MR-linac plans and CBCT-plans pre- and post-delivery and did not significantly differ. The percentage of plans that met all dose constraints was improved from 19% to 84% and 20% to 67% for single and multiple lymph node cases, respectively. CONCLUSION: Target coverage and dose criteria based evaluation of the first clinical 1.5T MR-linac SBRT treatments of lymph node oligometastases compared with conventional CBCT-linac treatment shows a smaller amount of unplanned violations of high dose criteria. The GTV coverage was comparable. Benefit is primarily gained in patients treated for multiple lymph node oligometastases: geometrical deformations are accounted for, dose can be delivered in one plan and margins can be reduced.

Individual lymph nodes: "See it and Zap it".

BACKGROUND AND PURPOSE: With magnetic resonance imaging (MRI)-guided radiotherapy systems such as the 1.5T MR-linac the daily anatomy can be visualized before, during and after radiation delivery. With these treatment systems, seeing metastatic nodes with MRI and zapping them with stereotactic body radiotherapy (SBRT) comes into reach. The purpose of this study is to investigate different online treatment planning strategies and to determine the planning target volume (PTV) margin needed for adequate target coverage when treating lymph node oligometastases with SBRT on the 1.5T MR-linac. MATERIALS AND METHODS: Ten patients were treated for single pelvic or para-aortic lymph node metastases on the 1.5T MR-linac with a prescribed dose of 5x7Gy with a 3 mm isotropic GTV- PTV margin. Based on the daily MRI and actual contours, a completely new treatment plan was generated for each session (adapt to shape, ATS). These were compared with plans optimized on pre-treatment CT contours after correcting for the online target position (adapt to position, ATP). At the end of each treatment session, a post-radiation delivery MRI was acquired on which the GTV was delineated to evaluate the GTV coverage and PTV margins. RESULTS: The median PTV V35Gy was 99.9% [90.7-100%] for the clinically delivered ATS plans compared to 93.6% [76.3-99.7%] when using ATP. The median GTV V35Gy during radiotherapy delivery was 100% [98-100%] on the online planning and post-delivery MRIs for ATS and 100% [93.9-100%] for ATP, respectively. The applied 3 mm isotropic PTV margin is considered adequate. CONCLUSION: For pelvic and para-aortic metastatic lymph nodes, online MRI-guided adaptive treatment planning results in adequate PTV and GTV coverage when taking the actual patient anatomy into account (ATS). Generally, GTV coverage remained adequate throughout the treatment session for both adaptive planning strategies. "Seeing and zapping" metastatic lymph nodes comes within reach for MRI-guided SBRT.

Adaptive radiotherapy: The Elekta Unity MR-linac concept.

BACKGROUND AND PURPOSE: The promise of the MR-linac is that one can visualize all anatomical changes during the course of radiotherapy and hence adapt the treatment plan in order to always have the optimal treatment. Yet, there is a trade-off to be made between the time spent for adapting the treatment plan against the dosimetric gain. In this work, the various daily plan adaptation methods will be presented and applied on a variety of tumour sites. The aim is to provide an insight in the behavior of the state-of-the-art 1.5 T MRI guided on-line adaptive radiotherapy methods. MATERIALS AND METHODS: To explore the different available plan adaptation workflows and methods, we have simulated online plan adaptation for five cases with varying levels of inter-fraction motion, regions of interest and target sizes: prostate, rectum, esophagus and lymph node oligometastases (single and multiple target). The plans were evaluated based on the clinical dose constraints and the optimization time was measured. RESULTS: The time needed for plan adaptation ranged between 17 and 485 s. More advanced plan adaptation methods generally resulted in more plans that met the clinical dose criteria. Violations were often caused by insufficient PTV coverage or, for the multiple lymph node case, a too high dose to OAR in the vicinity of the PTV. With full online replanning it was possible to create plans that met all clinical dose constraints for all cases. CONCLUSION: Daily full online replanning is the most robust adaptive planning method for Unity. It is feasible for specific sites in clinically acceptable times. Faster methods are available, but before applying these, the specific use cases should be explored dosimetrically.

Evaluation of plan adaptation strategies for stereotactic radiotherapy of lymph node oligometastases using online magnetic resonance image guidance.

BACKGROUND AND PURPOSE: Recent studies have shown that the use of magnetic resonance (MR) guided online plan adaptation yields beneficial dosimetric values and reduces unplanned violations of the dose constraints for stereotactic body radiation therapy (SBRT) of lymph node oligometastases. The purpose of this R-IDEAL stage 0 study was to determine the optimal plan adaptation approach for MR-guided SBRT treatment of lymph node oligometastases. MATERIALS AND METHODS: Using pre-treatment computed tomography (CT) and repeated MR data from five patients with in total 17 pathological lymph nodes, six different methods of plan adaptation were performed on the daily MRI and contours. To determine the optimal plan adaptation approach for treatment of lymph node oligometastases, the adapted plans were evaluated using clinical dose criteria and the time required for performing the plan adaptation. RESULTS: The average time needed for the different plan adaptation methods ranged between 11 and 119 s. More advanced adaptation methods resulted in more plans that met the clinical dose criteria [range, 0-16 out of 17 plans]. The results show a large difference between target coverage achieved by the different plan adaptation methods. CONCLUSION: Results suggested that multiple plan adaptation methods, based on plan adaptation on the daily anatomy, were feasible for MR-guided SBRT treatment of lymph node oligometastases. The most advanced method, in which a full online replanning was performed by segment shape and weight optimization after fluence optimization, yielded the most favourable dosimetric values and could be performed within a time-frame acceptable (<5 min) for MR-guided treatment.