Simulated daily plan adaptation for magnetic resonance-guided liver stereotactic body radiotherapy.

INTRODUCTION: Liver cancers are challenging to treat using image-guided radiotherapy (IGRT) due to motion and deformation of target volumes and organs at risk (OARs), as well as difficulties in visualising liver tumours using cone-beam computed tomography (CBCT) based IGRT. Liver cancer patients may thus benefit from magnetic resonance (MR)-guided daily adaptive re-planning. We evaluated the dosimetric impact of a daily plan adaptation strategy based on daily MR imaging versus CBCT-based IGRT. METHODS: Ten patients were studied who were treated with CBCT-guided five-fraction stereotactic body radiotherapy (SBRT) and underwent MR imaging before each fraction. Simulated reference plans were created on computer tomography (CT) images and adapted plans were created on the daily MR images. Two plan adaptation strategies were retrospectively simulated: (1) translational couch shifts to match liver, mimicking standard CBCT guidance and (2) daily plan adaptation based on reference plan clinical goals and daily target and OAR contours. Dose statistics were calculated for both strategies and compared. RESULTS: Couch shifts resulted in an average reduction in GTV D99% relative to reference plan values of 5.2 Gy (-12.5% of reference values). Daily plan adaptation reduced this to 0.8 Gy (-2.0%). For six patients who were OAR dose-limited on reference plans, couch shifts resulted in OAR dose violations in 28 out of 28 simulated fractions, respectively; no violations occurred using daily plan adaptation. No OAR dose violations occurred using either strategy for the four cases not OAR dose-limited at reference planning. CONCLUSIONS: MR-guided daily plan adaptation ensured OAR dose constraints were met at all simulated treatment fractions while CBCT-based IGRT resulted in a systematic over-dosing of OARs in patients whose doses were limited by OAR dose at the time of reference planning.

Development and validation of an MR-driven dose-of-the-day procedure for online adaptive radiotherapy in upper gastrointestinal cancer patients.

Objective.To develop and validate a dose-of-the-day (DOTD) treatment plan verification procedure for liver and pancreas cancer patients treated with an magnetic resonance (MR)-Linac system.Approach.DOTD was implemented as an automated process that uses 3D datasets collected during treatment delivery. Particularly, the DOTD pipeline's input included the adapt-to-shape (ATS) plan-i.e. 3D-MR dataset acquired at beginning of online session, anatomical contours, dose distribution-and 3D-MR dataset acquired during beam-on (BON). The DOTD automated analysis included (a) ATS-to-BON image intensity-based deformable image registration (DIR), (b) ATS-to-BON contours mapping via DIR, (c) BON-to-ATS contours copying through rigid registration, (d) determining ATS-to-BON dosimetric differences, and (e) PDF report generation. The DIR process was validated by two expert reviewers. ATS-plans were recomputed on BON datasets to assess dose differences. DOTD analysis was performed retrospectively for 75 treatment fractions (12-liver and 5-pancreas patients).Main results.The accuracy of DOTD process relied on DIR and mapped contours quality. Most DIR-generated contours (99.6%) were clinically acceptable. DICE correlated with depreciation of DIR-based region of interest mapping process. The ATS-BON plan difference was found negligible (<1%). The duodenum and large bowel exhibited highest variations, 24% and 39% from fractional values, for 5-fraction liver and pancreas. For liver 1-fraction, a 62% variation was observed for duodenum.Significance.The DOTD methodology provides an automated approach to quantify 3D dosimetric differences between online plans and their delivery. This analysis offers promise as a valuable tool for plan quality assessment and decision-making in the verification stage of the online workflow.

Prospective evaluation of patient-reported anxiety and experiences with adaptive radiation therapy on an MR-linac.

Purpose: An integrated magnetic resonance scanner and linear accelerator (MR-linac) was implemented with daily online adaptive radiation therapy (ART). This study evaluated patient-reported experiences with their overall hospital care as well as treatment in the MR-linac environment. Methods: Patients pre-screened for MR eligibility and claustrophobia were referred to simulation on a 1.5 T MR-linac. Patient-reported experience measures were captured using two validated surveys. The 15-item MR-anxiety questionnaire (MR-AQ) was administered immediately after the first treatment to rate MR-related anxiety and relaxation. The 40-item satisfaction with cancer care questionnaire rating doctors, radiation therapists, the services and care organization and their outpatient experience was administered immediately after the last treatment using five-point Likert responses. Results were analyzed using descriptive statistics. Results: 205 patients were included in this analysis. Multiple sites were treated across the pelvis and abdomen with a median treatment time per fraction of 46 and 66 min respectively. Patients rated MR-related anxiety as "not at all" (87%), "somewhat" (11%), "moderately" (1%) and "very much so" (1%). Positive satisfaction responses ranged from 78 to 100% (median 93%) across all items. All radiation therapist-specific items were rated positively as 96-100%. The five lowest rated items (range 78-85%) were related to general provision of information, coordination, and communication. Overall hospital care was rated positively at 99%. Conclusion: In this large, single-institution prospective cohort, all patients had low MR-related anxiety and completed treatment as planned despite lengthy ART treatments with the MR-linac. Patients overall were highly satisfied with their cancer care involving ART using an MR-linac.

Treatment planning for MR-guided SBRT of pancreatic tumors on a 1.5 T MR-Linac: A global consensus protocol.

Background and purpose: Treatment planning for MR-guided stereotactic body radiotherapy (SBRT) for pancreatic tumors can be challenging, leading to a wide variation of protocols and practices. This study aimed to harmonize treatment planning by developing a consensus planning protocol for MR-guided pancreas SBRT on a 1.5 T MR-Linac. Materials and methods: A consortium was founded of thirteen centers that treat pancreatic tumors on a 1.5 T MR-Linac. A phased planning exercise was conducted in which centers iteratively created treatment plans for two cases of pancreatic cancer. Each phase was followed by a meeting where the instructions for the next phase were determined. After three phases, a consensus protocol was reached. Results: In the benchmarking phase (phase I), substantial variation between the SBRT protocols became apparent (for example, the gross tumor volume (GTV) D99% ranged between 36.8 - 53.7 Gy for case 1, 22.6 - 35.5 Gy for case 2). The next phase involved planning according to the same basic dosimetric objectives, constraints, and planning margins (phase II), which led to a large degree of harmonization (GTV D99% range: 47.9-53.6 Gy for case 1, 33.9-36.6 Gy for case 2). In phase III, the final consensus protocol was formulated in a treatment planning system template and again used for treatment planning. This not only resulted in further dosimetric harmonization (GTV D99% range: 48.2-50.9 Gy for case 1, 33.5-36.0 Gy for case 2) but also in less variation of estimated treatment delivery times. Conclusion: A global consensus protocol has been developed for treatment planning for MR-guided pancreatic SBRT on a 1.5 T MR-Linac. Aside from harmonizing the large variation in the current clinical practice, this protocol can provide a starting point for centers that are planning to treat pancreatic tumors on MR-Linac systems.

MRI-Guided Online Adaptive Stereotactic Body Radiation Therapy of Liver and Pancreas Tumors on an MR-Linac System.

PURPOSE: To describe a comprehensive workflow for MRI-guided online adaptive stereotactic body radiation therapy (SBRT) specific to upper gastrointestinal cancer patients with abdominal compression on a 1.5T MR-Linac system. Additionally, we discuss the workflow's clinical feasibility and early experience in the case of 16 liver and pancreas patients. METHODS: Eleven patients with liver cancer and five patients with pancreas cancer were treated with online adaptive MRI-guidance under abdominal compression. Two liver patients received single-fraction treatments; the remainder plus all pancreas cancer patients received five fractions. A total of 65 treatment sessions were investigated to provide analytics relevant to the online adaptive processes. The quantification of target and organ motion as well as definition and validation of internal target volume (ITV) margins were performed via multi-contrast imaging provided by three different 2D cine sequences. The plan generation was driven by full re-optimization strategies and using T2-weighted 3D image series acquired by means of a respiratory-triggered exhale phase or a time-averaged imaging protocol. As a pre-requisite for the clinical development of the procedure, the image quality was thoroughly investigated via phantom measurements and numerical simulations specific to upper abdominal sites. The delivery of the online adaptive treatments was facilitated by real-time monitoring with 2D cine imaging. RESULTS: Liver 1-fraction and 5-fraction online adaptive session time were on average 80 and 67.5 min, respectively. The total session length varied between 70-90 min for a single fraction and 55-90 min for five fractions. The pancreas sessions were 54-85 min long with an average session time of 68.2 min. Target visualization on the 2D cine image data varied per patient, with at least one of the 2D cine sequences providing sufficient contrast to confidently identify its location and confirm reproducibility of ITV margins. The mean/range of absolute and relative dose values for all treatment sessions evaluated with ArcCheck were 90.6/80.9-96.1% and 99/95.4-100%, respectively. CONCLUSION: MR-guidance is feasible for liver and pancreas tumors when abdominal compression is used to reduce organ motion, improve imaging quality, and achieve a robust intra- and inter-fraction patient setup. However, the treatment length is significantly longer than for the conventional linac, and patient compliance is paramount for the successful completion of the treatment. Opportunities for reducing the online adaptive session time should be explored. As the next steps, dose-of-the-day and dose accumulation analysis and tools are needed to enhance the workflow and to help further refine the online re-planning processes.

Patient-Reported and Clinical Outcomes From 5-Fraction SBRT for Oligometastases: A Prospective Single-Institution Study.

PURPOSE: To describe the long-term outcomes of a 5-fraction normal tissue tolerance adapted strategy for the management of oligometastases (OM). METHODS AND MATERIALS: Patients with histologically confirmed solid tumors, ≤5 extracranial metastases, suitable for a definitive approach for all metastatic lesions, at least one lesion suitable for Stereotactic Body Radiotherapy (SBRT), Eastern Coooperative Oncology Group Performance Status ≤2 were eligible. Treatment intervention was a 5-fraction (25-55 Gy) normal tissue adapted dosing strategy. The primary outcome was cumulative local progression rate at 12 months. RESULTS: Between March 2013 and January 2018, 137 patients started SBRT. Median follow-up was 35.7 months. In addition, 107 (78%) patients had a solitary OM. The mean planning target volume D95 was 39.6 (standard deviation, 8.8; biological effective dose using an alpha/beta ratio of 10, 70.8) Gy. Mean planning target volume D95 was highest for lung lesions (48.7 [standard deviation, 4.7]; biological effective dose using an alpha/beta ratio of 10, 96.1) Gy but was <40 Gy for all other anatomic sites. Two grade 3 toxicities (gastrointestinal bleed) were observed with stomach D0.05 30.3 Gy and 30.4 Gy. The cumulative local progression rate at 12 of 36 months was 16.1% (95% CI, 10-22) and 38.3% (95% CI 30-46.7); overall survival was 90% and 37%, and progression free survival was 58% and 19%, respectively. Mean symptom burden (Edmonton Symptom Assessment Total Score) worsened in patients with progressive disease (+8.8) at 12 months and was paralleled by changes in mean European Organization for Research and Treatment Quality of Life Core Questionnaire Summary Score and Global Health Quality of Life Score. Systemic therapy was initiated in 55% of patients at an average of 12.7 (standard deviation 12.4) months. CONCLUSIONS: If long-term progression free survival is the primary goal of therapy, SBRT for OM achieved this in <20% of patients attributable to a high risk of distant failure. Favorable local progression free survival is accompanied by preservation of quality of life, avoidance of symptom progression and reduced need of antineoplastic therapies at 12 months. Information on symptom burden, quality of life, as well as pattern of antineoplastic therapy use after progressive disease is useful to support conversations between patients, families, and health care providers. Strategies to improve patient selection and reduce distant progression rate remain a priority for further study.

The Raystation conversation: Multidisciplinary perceptions about training, leadership, and communication during implementation of new technology.

PURPOSE: There is very little information guiding cancer centres as they plan for costly and time consuming implementation programs for new technology. The purpose of this research was to explore the perspectives of multiple professional groups directly involved in the implementation of a next generation treatment planning system at a large academic cancer centre . METHODS: This research was a single centre, prospective study using a qualitative design and three-phased approach (interviews, questionnaire, and focus groups). The target population included radiation therapists, oncologists, and physicists that received Raystation training during initial clinical implementation. RESULTS: Training was received positively by most respondents, but the lengthy lead-up time between training and clinical use led to decreased confidence with the software across all professional groups. Multidisciplinary training was not considered useful when learning tool function, but would have been helpful when practicing on clinically relevant cases. Respondents appreciated the proactive communication, as well as the multidisciplinary leadership implementation strategy. Therapist 'Super Users' emerged as a pivotal leadership and communication role in the successful implementation of Raystation. CONCLUSIONS: This research provided valuable multidisciplinary insight into the implementation of Raystation. The multidisciplinary leadership team and proactive communication strategy were considered vital to the success of the implementation. Learner suggestions - such as increasing the number of Therapist 'Super Users', minimizing training-to-clinical lead time, and the creation of practice cases that are more relevant to daily clinical duties - should be incorporated into future training programs for similar new technology.

Simulated dose painting of hypoxic sub-volumes in pancreatic cancer stereotactic body radiotherapy.

Dose painting of hypoxic tumour sub-volumes using positron-emission tomography (PET) has been shown to improve tumour controlin silicoin several sites, predominantly head and neck and lung cancers. Pancreatic cancer presents a more stringent challenge, given its proximity to critical gastro-intestinal organs-at-risk (OARs), anatomic motion, and impediments to reliable PET hypoxia quantification. A radiobiological model was developed to estimate clonogen survival fraction (SF), using18F-fluoroazomycin arabinoside PET (FAZA PET) images from ten patients with unresectable pancreatic ductal adenocarcinoma to quantify oxygen enhancement effects. For each patient, four simulated five-fraction stereotactic body radiotherapy (SBRT) plans were generated: (1) a standard SBRT plan aiming to cover the planning target volume with 40 Gy, (2) dose painting plans delivering escalated doses to a maximum of three FAZA-avid hypoxic sub-volumes, (3) dose painting plans with simulated spacer separating the duodenum and pancreatic head, and (4), plans with integrated boosts to geometric contractions of the gross tumour volume (GTV). All plans saturated at least one OAR dose limit. SF was calculated for each plan and sensitivity of SF to simulated hypoxia quantification errors was evaluated. Dose painting resulted in a 55% reduction in SF as compared to standard SBRT; 78% with spacer. Integrated boosts to hypoxia-blind geometric contractions resulted in a 41% reduction in SF. The reduction in SF for dose-painting plans persisted for all hypoxia quantification parameters studied, including registration and rigid motion errors that resulted in shifts and rotations of the GTV and hypoxic sub-volumes by as much as 1 cm and 10 degrees. Although proximity to OARs ultimately limited dose escalation, with estimated SFs (∼10-5) well above levels required to completely ablate a ∼10 cm3tumour, dose painting robustly reduced clonogen survival when accounting for expected treatment and imaging uncertainties and thus, may improve local response and associated morbidity.

The Effect of Lumpectomy Cavity Changes on Planning Dose in Breast Radiotherapy Boost.

INTRODUCTION: The addition of a postoperative tumour bed (cavity) boost after whole-breast radiotherapy (RT) is known to decrease the risk of local in-breast recurrence. The purpose of this retrospective study is to assess breast excision cavity changes and planned doses at the time of initial boost RT treatments after the completion of whole-breast RT. METHODS: Over a 4-month period, women with highly visible cavity on computed tomography (CT) and treated with whole-breast RT followed by a conformal photon boost to the tumour bed were identified. The patient's day 1 boost online cone beam CT (CBCT) and corresponding setup corrections were overlaid with the planning CT image. The cavity and dose evaluation volumes (DEVs = 1 cm expansion of the cavity, excluding 5 mm of lung and skin) were assessed. Dosimetric evaluations were performed for maximum and minimum cavity doses, cavity volume receiving 90% (V90) and 95% (V95) of prescription dose, and DEV receiving 85% (V85), 95%, and 105% (V105) of the prescription dose. The two-tailed student t-test and Pearson's correlation test were performed for statistical analysis. RESULTS: Eighteen patients were included in the analysis. The CT cavity (CAVCT) volume (mean: 28.8 cc, SD 27.9) was larger than the CBCT cavity (CAVCBCT) volume (mean: 21.1 cc, SD: 22.4) (P value= .003). The CT DEV similarly decreased at the time of boost; DEVCT (mean: 113.9 cc, SD: 63.2) versus DEVCBCT (mean: 92.3 cc, SD: 50.8), (P = .002). A strong correlation was observed between the initial CT cavity volume and cavity shrinkage observed at time of boost (day 1 CBCT) (Pearson's r = 0.697; r2= 0.486, P = .001). Both time periods from surgery to CT (median: 92 days, range: 31-227) and from surgery to day 1 CBCT (median: 141 days, range: 56-265) were not associated with cavity volume change. However, an inverse correlation was observed between time from initial CT to day 1 boost CBCT (median: 33 days, range: 24-54) and % cavity volume change (Pearson's r = -0.642; r2= 0.4121, P = .004). Dosimetric evaluations of the cavity and DEV showed no significant differences in maximum, minimum, and target dose coverage between the CT and boost volumes. CONCLUSION: In patients with breast cancer treated with a tumour bed boost after whole-breast RT, the postoperative cavity can shrink between the time of CT and day 1 boost. The extent of cavity reduction was greatest in patients with large postoperative cavities on initial CT. Despite the cavity size change, conformal boost fields provide adequate dose coverage to the cavity.

Treating Too Lightly? Radiation Therapists' Experiences of Workplace Violence When Providing Care to Cancer Patients and Their Families.

INTRODUCTION: Workplace violence (WPV) is defined as any act in which a person is abused, threatened, intimidated, or assaulted during their employment. Despite an absence of published evidence, radiation therapists (RTs) are considered a "low-risk" profession for WPV. The aim of this research was to determine the incidence, severity, and impact of WPV on RTs perpetrated by patients and/or their caregivers. MATERIALS AND METHODS: A cross-sectional online questionnaire, based on established components of WPV, was distributed via e-mail to all RTs in a large, urban cancer clinic. The questionnaire was divided into the five categories of WPV and asked about the frequency, severity, perpetrator, location, and impact of WPV. RESULTS: Seventy-eight responses were received from a department of 165 RTs (47% response rate). Fifty-nine RTs reported experiencing at least one verbal abuse event during their career. Twenty-five reported experiencing a verbal threat at least once, 46 reported at least one occasion of harassing behaviour, and 18 experienced a threatening action at least once. Five RTs reported suffering from at least one physical assault. The majority of this WPV took place on the treatment unit, with the patient as the perpetrator, and was not reported by the RT. High numbers of RTs reported suffering from stress (35), frustration (34), and anxiety (29) as a consequence of WPV. CONCLUSIONS: The close, longitudinal relationship between RTs and cancer patients puts RTs at considerable risk of experiencing multiple WPV events during their career. WPV is infrequently reported by RTs, perhaps linked to the belief that excellent patient care requires you to accept and excuse poor behaviour by patients. Prevention programs and de-escalation training are needed for RTs, but short-term measures such as shift or unit changes may prevent multiple WPV exposures which are associated with an increased risk of emotional and psychological sequelae.

Serial 4DCT/4DPET imaging to predict and monitor response for locally-advanced non-small cell lung cancer chemo-radiotherapy.

BACKGROUND AND PURPOSE: A FDG-PET/CT image feature with optimal prognostic potential for locally-advanced non-small cell lung cancer (LA-NSCLC) patients has yet to be identified, and neither has the optimal time for FDG-PET/CT response assessment; furthermore, nodal features have been largely ignored in the literature. We propose to identify image features or imaging time point with maximal prognostic power. MATERIALS AND METHODS: Consecutive consenting patients with LA-NSCLC receiving curative intent CRT were enrolled. 4DPET/4DCT scans were acquired 0, 2, 4, and 7 weeks during IMRT treatment. Eleven image features and their rates of change were recorded for each time point and tested for each of the possible outcome 2 years post CRT using the Kaplan-Meier method. RESULTS: 32 consecutive patients were recruited, 27 completing all scans. Restricting analysis to 4DPET/4DCT features and rates of change with p < 0.005, several volume-based features and their rates of change reached significance. Image features involving nodal disease were the only ones associated with overall survival. CONCLUSIONS: Several 4DPET/CT features and rates of change can reach significant association (p < 0.005) with outcomes, including overall survival, at many time points. The optimal time for adaptive CRT is therefore not constrained uniquely on imaging.