Adaptive MRI-guided stereotactic body radiation therapy for locally advanced pancreatic cancer - A phase II study.

PURPOSE: Stereotactic body radiotherapy (SBRT) has emerged as a promising new modality for locally advanced pancreatic cancer (LAPC). The current study evaluated the efficacy and toxicity of SBRT in patients with LAPC (NCT03648632). METHODS: This prospective single institution phase II study recruited patients with histologically or cytologically proven adenocarcinoma of the pancreas after more than two months of combination chemotherapy with no sign of progressive disease. Patients were prescribed 50-60 Gy in 5-8 fractions. Patients were initially treated on a standard linac (n = 4). Since 2019, patients were treated using online magnetic resonance (MR) image-guidance on a 1.5 T MRI-linac, where the treatment plan was adapted to the anatomy of the day. The primary endpoint was resection rate. RESULTS: Twenty-eight patients were enrolled between August 2018 and March 2022. All patients had non-resectable disease at time of diagnosis. Median follow-up from inclusion was 28.3 months (95 % CI 24.0-NR). Median progression-free and overall survival from inclusion were 7.8 months (95 % CI 5.0-14.8) and 16.5 months (95 % CI 10.7-22.6), respectively. Six patients experienced grade III treatment-related adverse events (jaundice, nausea, vomiting and/or constipation). One of the initial four patients receiving treatment on a standard linac experienced a grade IV perforation of the duodenum. Six patients (21 %) underwent resection. A further one patient was offered resection but declined. CONCLUSION: This study demonstrates that SBRT in patients with LAPC was associated with promising overall survival and resection rates. Furthermore, SBRT was safe and well tolerated, with limited severe toxicities.

Safety and Tolerability of Online Adaptive High-Field Magnetic Resonance-Guided Radiotherapy.

Importance: In 2018, the first online adaptive magnetic resonance (MR)-guided radiotherapy (MRgRT) system using a 1.5-T MR-equipped linear accelerator (1.5-T MR-Linac) was clinically introduced. This system enables online adaptive radiotherapy, in which the radiation plan is adapted to size and shape changes of targets at each treatment session based on daily MR-visualized anatomy. Objective: To evaluate safety, tolerability, and technical feasibility of treatment with a 1.5-T MR-Linac, specifically focusing on the subset of patients treated with an online adaptive strategy (ie, the adapt-to-shape [ATS] approach). Design, Setting, and Participants: This cohort study included adults with solid tumors treated with a 1.5-T MR-Linac enrolled in Multi Outcome Evaluation for Radiation Therapy Using the MR-Linac (MOMENTUM), a large prospective international study of MRgRT between February 2019 and October 2021. Included were adults with solid tumors treated with a 1.5-T MR-Linac. Data were collected in Canada, Denmark, The Netherlands, United Kingdom, and the US. Data were analyzed in August 2023. Exposure: All patients underwent MRgRT using a 1.5-T MR-Linac. Radiation prescriptions were consistent with institutional standards of care. Main Outcomes and Measures: Patterns of care, tolerability, and technical feasibility (ie, treatment completed as planned). Acute high-grade radiotherapy-related toxic effects (ie, grade 3 or higher toxic effects according to Common Terminology Criteria for Adverse Events version 5.0) occurring within the first 3 months after treatment delivery. Results: In total, 1793 treatment courses (1772 patients) were included (median patient age, 69 years [range, 22-91 years]; 1384 male [77.2%]). Among 41 different treatment sites, common sites were prostate (745 [41.6%]), metastatic lymph nodes (233 [13.0%]), and brain (189 [10.5%]). ATS was used in 1050 courses (58.6%). MRgRT was completed as planned in 1720 treatment courses (95.9%). Patient withdrawal caused 5 patients (0.3%) to discontinue treatment. The incidence of radiotherapy-related grade 3 toxic effects was 1.4% (95% CI, 0.9%-2.0%) in the entire cohort and 0.4% (95% CI, 0.1%-1.0%) in the subset of patients treated with ATS. There were no radiotherapy-related grade 4 or 5 toxic effects. Conclusions and Relevance: In this cohort study of patients treated on a 1.5-T MR-Linac, radiotherapy was safe and well tolerated. Online adaptation of the radiation plan at each treatment session to account for anatomic variations was associated with a low risk of acute grade 3 toxic effects.

Heart and Lung Dose as Predictors of Overall Survival in Patients With Locally Advanced Lung Cancer. A National Multicenter Study.

Introduction: It is an ongoing debate how much lung and heart irradiation impact overall survival (OS) after definitive radiotherapy for lung cancer. This study uses a large national cohort of patients with locally advanced NSCLC to investigate the association between OS and irradiation of lung and heart. Methods: Treatment plans were acquired from six Danish radiotherapy centers, and patient characteristics were obtained from national registries. A hybrid segmentation tool automatically delineated the heart and substructures. Dose-volume histograms for all structures were extracted and analyzed using principal component analyses (PCAs). Parameter selection for a multivariable Cox model for OS prediction was performed using cross-validation based on bootstrapping. Results: The population consisted of 644 patients with a median survival of 26 months (95% confidence interval [CI]: 24-29). The cross-validation selected two PCA variables to be included in the multivariable model. PCA1 represented irradiation of the heart and affected OS negatively (hazard ratio, 1.14; 95% CI: 1.04-1.26). PCA2 characterized the left-right balance (right atrium and left ventricle) irradiation, showing better survival for tumors near the right side (hazard ratio, 0.92; 95% CI: 0.84-1.00). Besides the two PCA variables, the multivariable model included age, sex, body-mass index, performance status, tumor dose, and tumor volume. Conclusions: Besides the classic noncardiac risk factors, lung and heart doses had a negative impact on survival, while it is suggested that the left side of the heart is a more radiation dose-sensitive region. The data indicate that overall heart irradiation should be reduced to improve the OS if possible.

MRI-guided radiotherapy in twenty fractions for localised prostate cancer; results from the MOMENTUM study.

Background and purpose: MRI-guided radiotherapy (MRIgRT) offers multiple potential advantages over CT-guidance. This study examines the potential clinical benefits of MRIgRT for men with localised prostate cancer, in the setting of moderately hypofractionated radiotherapy. We evaluate two-year toxicity outcomes, early biochemical response and patient-reported outcomes (PRO), using data obtained from a multicentre international registry study, for the first group of patients with prostate cancer who underwent treatment on a 1.5 T MR-Linac. Materials and methods: Patients who were enrolled within the MOMENTUM study and received radical treatment with 60 Gy in 20 fractions were identified. PSA levels and CTCAE version 5.0 toxicity data were measured at follow-up visits. Those patients who consented to PRO data collection also completed EQ-5D-5L, EORTC QLQ-C30 and EORTC QLQ-PR25 questionnaires. Results: Between November 2018 and June 2022, 146 patients who had MRIgRT for localised prostate cancer on the 1.5 T MR-Linac were eligible for this study. Grade 2 and worse gastro-intestinal (GI) toxicity was reported in 3 % of patients at three months whilst grade 2 and worse genitourinary (GU) toxicity was 7 % at three months. There was a significant decrease in the median PSA at 12 months. The results from both the EQ-5D-5L data and EORTC global health status scale indicate a decline in the quality of life (QoL) during the first six months. The mean change in score for the EORTC scale showed a decrease of 11.4 points, which is considered clinically important. QoL improved back to baseline by 24 months. Worsening of hormonal symptoms in the first six months was reported with a return to baseline by 24 months and sexual activity in all men worsened in the first three months and returned to baseline at 12 months. Conclusion: This study establishes the feasibility of online-MRIgRT for localised prostate on a 1.5 T MR-Linac with low rates of toxicity, similar to that published in the literature. However, the clinical benefits of MRIgRT over conventional radiotherapy in the setting of moderate hypofractionation is not evident. Further research will focus on the delivery of ultrahypofractionated regimens, where the potential advantages of MRIgRT for prostate cancer may become more discernible.

Radiation therapy in older patients with cancer.

The general population is aging, which expectedly will lead to a future increase in older patients with cancer. This review summarises the recent advances in radiotherapy. Technological advances have led radiotherapy to be an efficient and well-tolerated treatment option in older patient with cancer. Studies show no difference in toxicity and disease control rates compared with the ones in younger patients with cancer. MR-guided radiotherapy, proton therapy, and integration of artificial intelligence in treatment planning represent the latest advances in the field of radiotherapy and hold potential to further improve the treatment of older patients with cancer.

MR-guided stereotactic radiotherapy of infra-diaphragmatic oligometastases: Evaluation of toxicity and dosimetric parameters.

BACKGROUND AND PURPOSE: The SOFT trial is a prospective, multicenter, phase 2 trial investigating magnetic resonance (MR)-guided stereotactic ablative radiotherapy (SABR) for abdominal, soft tissue metastases in patients with oligometastatic disease (OMD) (clinicaltrials.gov ID NCT04407897). We present the primary endpoint analysis of 1-year treatment-related toxicity (TRAE). MATERIALS AND METHODS: Patients with up to five oligometastases from non-hematological cancers were eligible for inclusion. A risk-adapted strategy prioritized fixed organs at risk (OAR) constraints over target coverage. Fractionation schemes were 45-67.5 Gy in 3-8 fractions. The primary endpoint was grade ≥ 4 TRAE within 12 months post-SABR. The association between the risk of gastrointestinal (GI) toxicity and clinical and dosimetric parameters was tested using a normal tissue complication probability model. RESULTS: We included 121 patients with 147 oligometastatic targets, mainly located in the liver (41 %), lymph nodes (35 %), or adrenal glands (14 %). Nearly half of all targets (48 %, n = 71) were within 10 mm of a radiosensitive OAR. No grade 4 or 5 TRAEs, 3.5 % grade 3 TRAEs, and 43.7 % grade 2 TRAEs were reported within the first year of follow-up. We found a significant association between grade ≥ 2 GI toxicity and the parameters GI OAR D0.1cc, D1cc, and D20cc. CONCLUSION: In this phase II study of MR-guided SABR of oligometastases in the infra-diaphragmatic region, we found a low incidence of toxicity despite half of the lesions being within 10 mm of a radiosensitive OAR. GI OAR D0.1cc, D1cc, and D20cc were associated with grade ≥ 2 GI toxicity.

Development of Prostate Bed Delineation Consensus Guidelines for Magnetic Resonance Image-Guided Radiotherapy and Assessment of Its Effect on Interobserver Variability.

PURPOSE: The use of magnetic resonance imaging (MRI) in radiotherapy planning is becoming more widespread, particularly with the emergence of MRI-guided radiotherapy systems. Existing guidelines for defining the prostate bed clinical target volume (CTV) show considerable heterogeneity. This study aimed to establish baseline interobserver variability (IOV) for prostate bed CTV contouring on MRI, develop international consensus guidelines, and evaluate its effect on IOV. METHODS AND MATERIALS: Participants delineated the CTV on 3 MRI scans, obtained from the Elekta Unity MR-Linac, as per their normal practice. Radiation oncologist contours were visually examined for discrepancies, and interobserver comparisons were evaluated against simultaneous truth and performance level estimation (STAPLE) contours using overlap metrics (Dice similarity coefficient and Cohen's kappa), distance metrics (mean distance to agreement and Hausdorff distance), and volume measurements. A literature review of postradical prostatectomy local recurrence patterns was performed and presented alongside IOV results to the participants. Consensus guidelines were collectively constructed, and IOV assessment was repeated using these guidelines. RESULTS: Sixteen radiation oncologists' contours were included in the final analysis. Visual evaluation demonstrated significant differences in the superior, inferior, and anterior borders. Baseline IOV assessment indicated moderate agreement for the overlap metrics while volume and distance metrics demonstrated greater variability. Consensus for optimal prostate bed CTV boundaries was established during a virtual meeting. After guideline development, a decrease in IOV was observed. The maximum volume ratio decreased from 4.7 to 3.1 and volume coefficient of variation reduced from 40% to 34%. The mean Dice similarity coefficient rose from 0.72 to 0.75 and the mean distance to agreement decreased from 3.63 to 2.95 mm. CONCLUSIONS: Interobserver variability in prostate bed contouring exists among international genitourinary experts, although this is lower than previously reported. Consensus guidelines for MRI-based prostate bed contouring have been developed, and this has resulted in an improvement in contouring concordance. However, IOV persists and strategies such as an education program, development of a contouring atlas, and further refinement of the guidelines may lead to additional improvements.

An open source auto-segmentation algorithm for delineating heart and substructures - Development and validation within a multicenter lung cancer cohort.

BACKGROUND AND PURPOSE: Irradiation of the heart in thoracic cancers raises toxicity concerns. For accurate dose estimation, automated heart and substructure segmentation is potentially useful. In this study, a hybrid automatic segmentation is developed. The accuracy of delineation and dose predictions were evaluated, testing the method's potential within heart toxicity studies. MATERIALS AND METHODS: The hybrid segmentation method delineated the heart, four chambers, three large vessels, and the coronary arteries. The method consisted of a nnU-net heart segmentation and partly atlas- and model-based segmentation of the substructures. The nnU-net training and atlas segmentation was based on lung cancer patients and was validated against a national consensus dataset of 12 patients with breast cancer. The accuracy of dose predictions between manual and auto-segmented heart and substructures was evaluated by transferring the dose distribution of 240 previously treated lung cancer patients to the consensus data set. RESULTS: The hybrid auto-segmentation method performed well with a heart dice similarity coefficient (DSC) of 0.95, with no statistically significant difference between the automatic and manual delineations. The DSC for the chambers varied from 0.78-0.86 for the automatic segmentation and was comparable with the inter-observer variability. Most importantly, the automatic segmentation was as precise as the clinical experts in predicting the dose distribution to the heart and all substructures. CONCLUSION: The hybrid segmentation method performed well in delineating the heart and substructures. The prediction of dose by the automatic segmentation was aligned with the manual delineations, enabling measurement of heart and substructure dose in large cohorts. The delineation algorithm will be available for download.

An open-source nnU-net algorithm for automatic segmentation of MRI scans in the male pelvis for adaptive radiotherapy.

Background: Adaptive MRI-guided radiotherapy (MRIgRT) requires accurate and efficient segmentation of organs and targets on MRI scans. Manual segmentation is time-consuming and variable, while deformable image registration (DIR)-based contour propagation may not account for large anatomical changes. Therefore, we developed and evaluated an automatic segmentation method using the nnU-net framework. Methods: The network was trained on 38 patients (76 scans) with localized prostate cancer and tested on 30 patients (60 scans) with localized prostate, metastatic prostate, or bladder cancer treated at a 1.5 T MRI-linac at our institution. The performance of the network was compared with the current clinical workflow based on DIR. The segmentation accuracy was evaluated using the Dice similarity coefficient (DSC), mean surface distance (MSD), and Hausdorff distance (HD) metrics. Results: The trained network successfully segmented all 600 structures in the test set. High similarity was obtained for most structures, with 90% of the contours having a DSC above 0.9 and 86% having an MSD below 1 mm. The largest discrepancies were found in the sigmoid and colon structures. Stratified analysis on cancer type showed that the best performance was seen in the same type of patients that the model was trained on (localized prostate). Especially in patients with bladder cancer, the performance was lower for the bladder and the surrounding organs. A complete automatic delineation workflow took approximately 1 minute. Compared with contour transfer based on the clinically used DIR algorithm, the nnU-net performed statistically better across all organs, with the most significant gain in using the nnU-net seen for organs subject to more considerable volumetric changes due to variation in the filling of the rectum, bladder, bowel, and sigmoid. Conclusion: We successfully trained and tested a network for automatically segmenting organs and targets for MRIgRT in the male pelvis region. Good test results were seen for the trained nnU-net, with test results outperforming the current clinical practice using DIR-based contour propagation at the 1.5 T MRI-linac. The trained network is sufficiently fast and accurate for clinical use in an online setting for MRIgRT. The model is provided as open-source.

Impact of abdominal compression on intra-fractional motion and delivered dose in magnetic resonance image-guided adaptive radiation ablation of adrenal gland metastases.

PURPOSE: The current study investigated the impact of abdominal compression on motion and the delivered dose during non-gated, magnetic resonance image (MRI)-guided radiation ablation of adrenal gland metastases. METHODS: Thirty-one patients with adrenal gland metastases treated to 45-60 Gy in 3-8 fractions on a 1.5 T MRI-linac were included in the study. The patients were breathing freely (n = 14) or with motion restricted by using an abdominal compression belt (n = 17). The time-resolved position of the target in online 2D cine MR images acquired during treatment was assessed and used to estimate the dose delivered to the GTV and abutting luminal organs at risk (OAR). RESULTS: The median (range) 3D root-mean-square target position error was significantly higher in patients treated without a compression belt [2.9 (1.9-5.6) mm] compared to patients using the belt [2.1 (1.2-3.5) mm] (P < 0.01). The median (range) GTV V95% was significantly reduced from planned 98.6 (65.9-100) % to delivered 96.5 (64.5-99.9) % due to motion (P < 0.01). Most prominent dose reductions were found in patients showing either large target drift or respiration motion and were mainly treated without abdominal compression. Motion did not lead to an increased number of constraint violations for luminal OAR. CONCLUSIONS: Acceptable target coverage and dose to OAR was observed in the vast majority of patients despite intra-fractional motion during adaptive MRI-guided radiation ablation. The use of abdominal compression significantly reduced the target position error and prevented the most prominent target coverage degradations and is, therefore, recommended as motion management at MRI-linacs.

5-Year survival in Danish patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitor monotherapy.

BACKGROUND: Convincing results from randomized controlled trials (RCTs) have led to increasing use of immune checkpoint inhibitors (ICI) as part of standard therapies in real-world (RW) scenarios. However, RW patients differ clinically from RCT populations and might have reduced long-term survival. Currently, only sparse data on 3-5-year survival rate for RW patients with advanced non-small cell lung cancer (NSCLC) treated with ICI exist. MATERIALS AND METHODS: A multicenter study was performed including 729 patients with advanced NSCLC receiving monotherapy with ICI (retrospective data (n = 566) and prospective data (n = 163)). Detailed baseline clinical characteristics, programmed death-ligand 1 (PD-L1) tumor proportion score (TPS), and baseline haematological count were registered. Kaplan-Meier estimates and log-rank test were used for survival analyses, Cox regression for determination of prognostic factors. RESULTS: Median time of follow-up (FU) was 48.7 months (IQR 37.2-54.3). Median overall survival (OS) in first line treatment was 20.4 months (IQR 8.5-45.0) compared to 11.4 months (IQR 4.6-27.1) in ≥2nd line (HR 1.48, 95% CI 1.25-1.75). Estimated probability of OS was 30% at 3 years, 23% at 4 years, and 13% at 5 years in first line compared to 17, 13, and 11% in ≥2nd line, respectively. For those with performance status (PS) 2, the 2-year OS rate was 32% (95% CI 0.22-0.43) compared to 5% (95% CI 0.01-0.15) in patients with PD-L1 ≥ 50% versus <50%, respectively. CONCLUSIONS: Compared to RCTs, long-term OS and PFS rates are lower in real-world patients treated with ICI in first line but much improved compared to historic rates on chemotherapy. A promising flattening of both the OS and progression free survival curves illustrates that also a subset of real-world patients obtain long-term remission. Patients with PS 2 and PD-L1 ≥ 50% may obtain clinically meaningful 2-year PFS and OS rates.

Radiotherapy for Locally Advanced Pancreatic Adenocarcinoma-A Critical Review of Randomised Trials.

Pancreatic cancer is rising as one of the leading causes of cancer-related death worldwide. Patients often present with advanced disease, limiting curative treatment options and therefore making management of the disease difficult. Systemic chemotherapy has been an established part of the standard treatment in patients with both locally advanced and metastatic pancreatic cancer. In contrast, the use of radiotherapy has no clear defined role in the treatment of these patients. With the evolving imaging and radiation techniques, radiation could become a plausible intervention. In this review, we give an overview over the available data regarding radiotherapy, chemoradiation, and stereotactic body radiation therapy. We performed a systematic search of Embase and the PubMed database, focusing on studies involving locally advanced pancreatic cancer (or non-resectable pancreatic cancer) and radiotherapy without any limitation for the time of publication. We included randomised controlled trials involving patients with locally advanced pancreatic cancer, including radiotherapy, chemoradiation, or stereotactic body radiation therapy. The included articles represented mainly small patient groups and had a high heterogeneity regarding radiation delivery and modality. This review presents conflicting results concerning the addition of radiation and modality in the treatment regimen. Further research is needed to improve outcomes and define the role of radiation therapy in pancreatic cancer.

Recommendations for improved reproducibility of ADC derivation on behalf of the Elekta MRI-linac consortium image analysis working group.

BACKGROUND AND PURPOSE: The apparent diffusion coefficient (ADC), a potential imaging biomarker for radiotherapy response, needs to be reproducible before translation into clinical use. The aim of this study was to evaluate the multi-centre delineation- and calculation-related ADC variation and give recommendations to minimize it. MATERIALS AND METHODS: Nine centres received identical diffusion-weighted and anatomical magnetic resonance images of different cancerous tumours (adrenal gland, pelvic oligo metastasis, pancreas, and prostate). All centres delineated the gross tumour volume (GTV), clinical target volume (CTV), and viable tumour volume (VTV), and calculated ADCs using both their local calculation methods and each of the following calculation conditions: b-values 0-500 vs. 150-500 s/mm2, region-of-interest (ROI)-based vs. voxel-based calculation, and mean vs. median. ADC variation was assessed using the mean coefficient of variation across delineations (CVD) and calculation methods (CVC). Absolute ADC differences between calculation conditions were evaluated using Friedman's test. Recommendations for ADC calculation were formulated based on observations and discussions within the Elekta MRI-linac consortium image analysis working group. RESULTS: The median (range) CVD and CVC were 0.06 (0.02-0.32) and 0.17 (0.08-0.26), respectively. The ADC estimates differed 18% between b-value sets and 4% between ROI/voxel-based calculation (p-values < 0.01). No significant difference was observed between mean and median (p = 0.64). Aligning calculation conditions between centres reduced CVC to 0.04 (0.01-0.16). CVD was comparable between ROI types. CONCLUSION: Overall, calculation methods had a larger impact on ADC reproducibility compared to delineation. Based on the results, significant sources of variation were identified, which should be considered when initiating new studies, in particular multi-centre investigations.

Does coronary artery calcium score have an impact on overall survival for locally advanced non-small cell lung cancer treated with definitive radiotherapy.

BACKGROUND AND PURPOSE: Coronary artery calcium score (CACs) is an excellent marker for survival in non-cancer patients, but its role in locally advanced non-small cell lung cancer (LA-NSCLC) patients remains uncertain. In this study, we hypothesize that CACs is a prognostic marker for survival in a competing risk analysis in LA-NSCLC patients treated with definitive radiotherapy. MATERIALS AND METHODS: We included 644 patients with LA-NSCLC treated in 2014-2015 in Denmark. Baseline patient characteristics were derived from the Danish Lung Cancer Registry. Radiotherapy planning CT scans were used for manual CACs measurements, and the patients were divided into four groups, CACs 0, 1-99, 100-399, and ≥400. A multivariable Cox model utilizing bootstrapping for cross-validation modeled overall survival (OS). RESULTS: The median follow-up time was seven years, and the median OS was 26 months (95% CI 24-29). Within each CAC group 0, 1-99, 100-399, and ≥400 were 172, 182, 143, and 147 patients, respectively. In the univariable analysis, the survival decreased with increasing CACs. However, after adjustment for age, PS, radiotherapy dose, and logarithmic GTV, CACs did not have a statistically significant impact on OS with hazard ratios of 1.04 (95% CI 0.85-1.28), 1.11 (95%CI 0.89-1.43), and 1.16 (95%CI 0.92-1.47) for CACs 1-99, CACs 100-399 and ≥400, respectively. Elevated CACs was observed in 73 % of the patients suggesting a high risk of cardiac comorbidity before radiotherapy. CONCLUSION: CACs did not add prognostic information to our population's classical risk factors, such as tumor volume, performance status, and age; the lung cancer has the highest priority despite the risk of baseline cardiac comorbidity.

Clinical impact of venous thromboembolism in non-small cell lung cancer patients receiving immunotherapy.

BACKGROUND: Prospective investigation on cancer-associated venous thromboembolism (VTE) in non-small cell lung cancer (NSCLC) during treatment with immune checkpoint inhibitors (ICIs) is lacking. PATIENTS AND METHODS: A prospective real-world study using combined computed tomography venography and pulmonary angiography (CTVPA) to screen patients with NSCLC for VTE (cohort A). A retrospective multicenter cohort without additional screening with CTVPA was included as control (cohort B). A model with VTE as a time-dependent event using competing risk analysis model with death as a competing event was used to evaluate outcomes and differences in cumulative VTE incidences. RESULTS: Cohort A (n = 146) and cohort B (n = 426) had median follow-up for VTE of 16.5 months (IQR 6.7-35.6). Cumulative VTE events at 1, 3, 6, and 12 months were 7.5 %, 9.6 %, 13.0 %, 14.4 % for cohort A and 1.9 %, 3.8 %, 4.9 %, 5.6 % for cohort B with SHR 2.42 (CI 95 % 1.37-4.27) p = 0.0024. Recurrent VTE comprised 52 % and 37 %, respectively. In multivariate overall survival analysis, VTE was significantly associated with impaired OS (HR 2.12 CI 95 % [1.49-3.03], p < 0.0001). Risk factors for VTE comprised prior VTE and ICI administered in first line. CONCLUSION: Cumulative VTE incidence in NSCLC patients following palliative ICI may be significantly higher than reported in randomised clinical trials and retrospective real-world reports. VTE development during ICI impair OS significantly. Thus, more focus on VTE during ICI is warranted to optimise both prevention and management of VTE. Whether there is a causal relationship between VTE and ICI remains to be explored.

Magnetic Resonance-Guided Adaptive Radiation Therapy for Prostate Cancer: The First Results from the MOMENTUM study-An International Registry for the Evidence-Based Introduction of Magnetic Resonance-Guided Adaptive Radiation Therapy.

PURPOSE: Magnetic resonance (MR)-guided radiation therapy (MRgRT) is a new technique for treatment of localized prostate cancer (PCa). We report the 12-month outcomes for the first PCa patients treated within an international consortium (the MOMENTUM study) on a 1.5T MR-Linac system with ultrahypofractionated radiation therapy. METHODS AND MATERIALS: Patients treated with 5 × 7.25 Gy were identified. Prostate specific antigen-level, physician-reported toxicity (Common Terminology Criteria for Adverse Events [CTCAE]), and patient-reported outcomes (Quality of Life Questionnaire PR25 and Quality of Life Questionnaire C30 questionnaires) were recorded at baseline and at 3, 6, and 12 months of follow-up (FU). Pairwise comparative statistics were conducted to compare outcomes between baseline and FU. RESULTS: The study included 425 patients with localized PCa (11.4% low, 82.0% intermediate, and 6.6% high-risk), and 365, 313, and 186 patients reached 3-, 6-, and 12-months FU, respectively. Median prostate specific antigen level declined significantly to 1.2 ng/mL and 0.1 ng/mL at 12 months FU for the nonandrogen deprivation therapy (ADT) and ADT group, respectively. The peak of genitourinary and gastrointestinal CTCAE toxicity was reported at 3 months FU, with 18.7% and 1.7% grade ≥2, respectively. The QLQ-PR25 questionnaire outcomes showed significant deterioration in urinary domain score at all FU moments, from 8.3 (interquartile range [IQR], 4.1-16.6) at baseline to 12.4 (IQR, 8.3-24.8; P = .005) at 3 months, 12.4 (IQR, 8.3-20.8; P = .018;) at 6 months, and 12.4 (IQR, 8.3-20.8; P = .001) at 12 months. For the non-ADT group, physician- and patient-reported erectile function worsened significantly between baseline and 12 months FU. CONCLUSIONS: Ultrahypofractionated MR-guided radiation therapy for localized PCa using a 1.5T MR-Linac is effective and safe. The peak of CTCAE genitourinary and gastrointestinal toxicity was reported at 3 months FU. Furthermore, for patients without ADT, a significant increase in CTCAE erectile dysfunction was reported at 12 months FU. These data are useful for educating patients on expected outcomes and informing study design of future comparative-effectiveness studies.

The effect of respiration-induced target motion on 3D magnetic resonance images used to guide radiotherapy.

Background and purpose: 3D Magnetic Resonance Imaging (MRI) is used in radiation therapy for reference planning and, lately, for adaptive treatments on MR accelerators. This study aimed to investigate the impact of different types of respiratory motion on the apparent target position and extent in such scans. Materials and methods: An MRI motion phantom with a 30 mm diameter target was used to simulate cranial-caudal (CC) motion and imaged at an MR-Linac using a standard clinically released 3D T2w sequence. Scans were acquired for each combination of functions (sin(t), sin4(t) and sin12(t)), peak-to-peak amplitudes (5, 10, 15 and 20 mm), and periods (4, 5 and 6 s). Furthermore, respiration CC motion patterns from two patients were used. Motion functions were shifted such that the time average target position would match a static reference scan at 0-position. The target was automatically identified in coronal and sagittal images using k-means clustering. The mean position and area of the target were calculated and compared to the reference scan. Results: Artefacts increased with amplitude and depended on the motion type. Sin(t) and sin4(t) oscillations resulted in a blurring of the target, which led to an increased target area, while sin12(t) motion did not show significant changes in the target area. However, for the sin12(t) motion, the offset in apparent position was prominent, while that was not the case for the sin(t) and sin4(t) motion. The patient respiration motion profiles showed similar trends. Conclusions: In 3D MRI, target motion can change apparent tumour extent and apparent position. The changes increase with motion amplitude and depend on the motion type.

Causal relation between heart irradiation and survival of lung cancer patients after radiotherapy.

INTRODUCTION: In a recent study, setup uncertainties in the direction of the heart were shown to impact the overall survival of non-small cell lung cancer (NSCLC) patients after radiotherapy, indicating the causal effect between heart irradiation and survival. The current study aims to externally evaluate this observation within a patient cohort treated using daily IGRT. METHOD: NSCLC patients with locally-advanced disease and daily CBCT were included. For all treatment fractions, the distance between the isocenter and the heart was evaluated based on the clinical setup registrations. The variation in heart position between planning and treatment (DeltaDistance) was estimated from these registrations. The possible impact of DeltaDistance on survival was analysed by a multivariable Cox model of overall survival, allowing for a time-dependent impact of DeltaDistance to allow for toxicity latency. RESULTS: Daily CBCT information was available for 489 patients at Odense University Hospital. The primary Cox model contained GTV volume, patient age, performance status, and DeltaDistance. DeltaDistance significantly impacted overall survival approximately 50 months after radiotherapy. Subanalyses indicated that the observed effect is mainly present among the patients with the least clinical risk factors. CONCLUSION: Our results confirm the impact of setup variations in the direction of the heart on the survival of NSCLC patients, even within a cohort using daily CBCT setup guidance. This result indicates a causal effect between heart irradiation and survival. It will be challenging to reduce the setup uncertainty even further; thus, increased focus on dose constraints on the heart seems warranted.

First multicentre experience of SABR for lymph node and liver oligometastatic disease on the unity MR-Linac.

The treatment of oligometastatic disease using MR guidance is an evolving field. Since August 2018 patients are treated on a 1.5 Tesla MR-Linac (MRL). We present current workflows and practice standards from seven institutions for the initial patients treated for lymph node and liver metastases.

Effect and Tolerability of Immunotherapy in Patients with NSCLC with or without Brain Metastasis.

Sparse data exist on immune checkpoint inhibition (ICI) in NSCLC patients with brain metastasis (BM), especially for those with no local therapy (LT) (whole brain radiation therapy (WBRT), stereotactic RT (SRT) or neurosurgery) preceding ICI. Our aims were to investigate the prevalence of BM, rate of intracranial response (ICR), and survival and quality of life (QoL) in real-life patients with advanced NSCLC undergoing palliative ICI. This was a prospective non-randomized study (NCT03870464) with magnetic resonance imaging of the brain (MR-C) performed at baseline resulting in a clinical decision to administer LT or not. ICR evaluation (MR-C) at week 8-9 (mRECIST criteria) for group A (LT) and group B (untreated) was assessed. Change in QoL was assessed using EQ-5D-5L. Of 159 included patients, 45 (28%) had baseline BM. Median follow-up was 23.2 months (IQR 16.4-30.2). Of patients in group A (21) and B (16), 16/37 (43%) had symptomatic BM. ICR was 8/21, 38% (complete or partial response) for group A versus 8/16, 50% for group B. No statistical difference in median overall survival of patients with BM (group A: 12.3 (5.2-NR), group B: 20.5 months (4.9-NR)) and without (22.4 months (95% 16.2-26.3)) was obtained. Baseline QoL was comparable regardless of BM, but an improved QoL (at week 9) was found in those without BM. Patients with NSCLC and BM receiving ICI had long-term survival comparable to those without BM.