Diagnosis and management of tropomyosin receptor kinase (TRK) fusion sarcomas: expert recommendations from the World Sarcoma Network.

Sarcomas are a heterogeneous group of malignancies with mesenchymal lineage differentiation. The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions as tissue-agnostic oncogenic drivers has led to new personalized therapies for a subset of patients with sarcoma in the form of tropomyosin receptor kinase (TRK) inhibitors. NTRK gene rearrangements and fusion transcripts can be detected with different molecular pathology techniques, while TRK protein expression can be demonstrated with immunohistochemistry. The rarity and diagnostic complexity of NTRK gene fusions raise a number of questions and challenges for clinicians. To address these challenges, the World Sarcoma Network convened two meetings of expert adult oncologists and pathologists and subsequently developed this article to provide practical guidance on the management of patients with sarcoma harboring NTRK gene fusions. We propose a diagnostic strategy that considers disease stage and histologic and molecular subtypes to facilitate routine testing for TRK expression and subsequent testing for NTRK gene fusions.

Is Peritoneal Tumor Penetration of Prognostic Importance in Gastrointestinal Stromal Tumors?

BACKGROUND: Peritoneal tumor penetration (PP) strongly affects prognosis in gastrointestinal carcinomas. In gastrointestinal stromal tumor (GIST), its significance in the absence of tumor rupture has not been subjected to detailed analysis. METHODS: Patients undergoing complete resection for non-metastatic GIST from 2000 to 2017 were identified in the regional sarcoma database at Oslo University Hospital. Patients with extraperitoneal tumors (esophagus, rectum) or ruptured tumors were excluded from the study. Rupture was defined according to the Oslo criteria, and PP was assessed via routine histopathologic examination by sarcoma pathologists. RESULTS: The study enrolled 341 patients. The median follow-up period was 51 months (range 0-175) months. In 82 (24%) of the 341 patients, PP was recorded. There were 32 recurrences, 9 in patients with PP and 23 in patients without PP. Despite statistically significant associations between PP and established risk factors (size, mitotic index, non-gastric location), the 5-year recurrence-free survival rate did not differ between the patients with PP (86%) and those without PP (90%) (hazard ratio 1.25; 95% confidence interval 0.58-2.70; P = 0.577). Adjuvant imatinib was administered to 53 of 97 patients in the high-risk category. The recurrence rates did not differ between the PP-positive and PP-negative patients in either group. CONCLUSIONS: In GIST, PP without tumor rupture appears not to influence prognosis. This lack of prognostic significance may reflect unexplored differences between epithelial and mesenchymal malignancies.

Relationship between R1 resection, tumour rupture and recurrence in resected gastrointestinal stromal tumour.

BACKGROUND: According to guidelines, adjuvant treatment or re-excision should be considered after R1 resection of gastrointestinal stromal tumours (GISTs). However, the prognostic significance of R1 resection is uncertain and tumour rupture confounds its assessment. Here, the impact of positive margins was examined and related to rupture in a population-based cohort. METHODS: Patients undergoing surgery for non-metastatic GIST since 2000 were identified in the sarcoma database of Oslo University Hospital. Margins were coded according to the residual tumour (R) classification and tumour rupture defined according to the Oslo criteria. RESULTS: Among 410 patients, there were 47 who underwent R1 resection and 52 had tumour rupture. The relative risk of R1 resection with rupture was 3·55 (95 per cent c.i. 2·09 to 6·03; P < 0·001). In patients without rupture, there was no difference in estimated 5-year recurrence-free survival after R0 versus R1 resection (87·6 versus 93 per cent; hazard ratio (HR) 0·71, 95 per cent c.i. 0·17 to 2·98; P = 0·638); nor was there any difference among patients with rupture (37 versus 31 per cent; HR 1·31, 0·68 to 2·54; P = 0·420). In multivariable analysis, tumour rupture but not R1 resection was independently associated with recurrence. Twenty-four patients at very low, low or intermediate risk did not receive adjuvant imatinib after R1 resection and remained recurrence-free. CONCLUSION: Positive resection margins are strongly associated with tumour rupture. R1 resection does not independently influence prognosis. Adjuvant imatinib may not be justified after R1 resection in the absence of tumour rupture or other high-risk features.

Genotype and risk of tumour rupture in gastrointestinal stromal tumour.

BACKGROUND: Tumour rupture is a strong predictor of poor outcome in gastrointestinal stromal tumours (GISTs) of the stomach and small intestine. The objective was to determine whether tumour genotype was associated with risk of rupture. METHODS: Rupture was classified according to the definition proposed by the Oslo Sarcoma Group. Since January 2000, data were registered retrospectively for all patients at Oslo University Hospital undergoing surgery for localized GIST of the stomach or small intestine. Tumour genotype was analysed by Sanger sequencing. RESULTS: Two hundred and nine patients with mutation data available were identified. Tumour rupture occurred in 37 patients. Among the 155 patients with KIT exon 11 mutations, an increased risk of rupture was observed with a deletion or insertion-deletion (25 of 86, 29 per cent) compared with substitutions (5 of 50, 10 per cent) or duplications/insertions (2 of 19, 11 per cent) (P = 0·014). Notably, rupture occurred in 17 of 46 tumours (37 per cent) with deletions involving codons 557 and 558 (del557/558) versus 15 of 109 (13·8 per cent) with other exon 11 mutations (P = 0·002). This association was confined to gastric tumours: 12 of 34 (35 per cent) with del557/558 ruptured versus six of 77 (8 per cent) with other exon 11 mutations (P = 0·001). In multivariable logistic regression analysis, del557/558 and tumour size were associated with an increased likelihood of tumour rupture, but mitotic count was not. CONCLUSION: Gastric GISTs with KIT exon 11 deletions involving codons 557 and 558 are at increased risk of tumour rupture. This high-risk feature can be identified in the diagnostic evaluation and should be included in the assessment when neoadjuvant imatinib treatment is considered.

Deep Pelvic Surgical Site Infection After Radiotherapy and Surgery for Locally Advanced Rectal Cancer.

BACKGROUND: High morbidity, increased mortality, and impaired long-term oncologic outcome have been reported after deep surgical site infection (SSI) in rectal cancer surgery. The rate, risk factors and consequences of deep SSI after (chemo)radiotherapy [(C)RT], and surgery for locally advanced rectal cancer (LARC) in a tertiary university hospital single centre cohort of 540 patients are presented. METHODS: Patients with LARC, operated between January 1, 2007 and December 31, 2015, were identified in the institutional prospective database. All patients had tumours threatening the mesorectal fascia or invading adjacent organs, with a high rate of T4 tumours (60 %), and all received (C)RT. Risk factors for deep SSI were calculated by multivariable logistic regression analysis. Morbidity data were assessed. Overall survival (OS) and disease-free survival (DFS) between patients with or without deep SSI were estimated. RESULTS: Of 540 patients, 104 (19 %) experienced a deep SSI, with the highest rate in the abdominoperineal resection (APR) group with 25 %. APR, good response to (C)RT (low tumour regression grade), age, and operative blood loss were identified as significant (P < 0.05) risk factors for deep SSI in multivariable analysis. No difference was found in OS (P = 0.995) or DFS (P = 0.568). Hospital stay increased with 5 days (P < 0.001), and complete wound healing at the 3-month follow-up decreased from 86 to 45 % (P < 0.001) after deep SSI. CONCLUSIONS: Deep SSI is a frequent and major complication after rectal surgery for LARC, with high morbidity, increased hospital stay and protracted wound healing. Interestingly, deep SSI did not influence long-term oncologic outcome.

Definition and clinical significance of tumour rupture in gastrointestinal stromal tumours of the small intestine.

BACKGROUND: Tumour rupture is a risk factor for recurrence of gastrointestinal stromal tumour (GIST). In this study, patterns of recurrence after potential tumour seeding were investigated, and a new definition of tumour rupture, based on major and minor defects of tumour integrity, is proposed. METHODS: Patients undergoing surgery for non-metastatic small intestinal GIST from 2000 to 2012 were included in the study. Tumour spillage, tumour fracture or piecemeal resection, bowel perforation at the tumour site, blood-tinged ascites, microscopic tumour infiltration into an adjacent organ, and surgical biopsy were defined as major defects of tumour integrity. Peritoneal tumour penetration, iatrogenic peritoneal laceration and microscopically involved margins were defined as minor defects. RESULTS: Seventy-two patients were identified. Median follow-up was 58 (range 7-122) months. Radical surgery was performed in 71 patients. A major defect was recorded in 20 patients, and a minor defect in 21. The 5-year recurrence rate was 64, 29 and 31 per cent in patients with major, minor and no defect respectively (P = 0·001). The hazard ratio (HR) for major defect versus no defect was 3·55 (95 per cent c.i. 1·51 to 8·35). Peritoneal recurrence rates for major, minor and no defect were 52, 25 and 19 per cent respectively (P = 0·002), and the HR for major defect versus no defect was 4·98 (1·69 to 14·68). On multivariable analysis, mitotic index, major defect of tumour integrity, tumour size and age were independently associated with risk of recurrence. CONCLUSION: Recurrence rates were increased after major, but not minor tumour ruptures.

Patient-reported outcome results in patients with type 2 diabetes treated with once-weekly dulaglutide: data from the AWARD phase III clinical trial programme.

We evaluated patient-reported outcome (PRO) measures from the Assessment of Weekly AdministRation of LY2189265 (dulaglutide) in Diabetes (AWARD) clinical trial programme for dulaglutide (1.5 mg and 0.75 mg) in patients with type 2 diabetes (T2D). The Impact of Weight on Self-Perception (IW-SP), Impact of Weight on Ability to Perform Physical Activities of Daily Living (APPADL), Impact of Weight on Quality of Life-Lite, EQ-5D, Diabetes Treatment Satisfaction Questionnaire (DTSQ), Diabetes Symptom Checklist-Revised and Adult Low Blood Sugar Survey were administered and analysed for changes from baseline in one or more AWARD studies. Significant within-group changes from baseline to the primary time point were observed for several PRO measures across all studies. Compared with insulin glargine, significantly greater improvements in the IW-SP score were observed with dulaglutide 1.5 mg and with both dulaglutide doses in the APPADL score. Both dulaglutide doses resulted in significantly greater improvement in DTSQ scores (all subscales) compared with exenatide. Dulaglutide 1.5 mg also resulted in significantly greater improvement on the DTSQ hyperglycaemia subscale compared with metformin. Overall, these PRO results suggest that dulaglutide is beneficial in the treatment of T2D.

Multi-country retrospective observational study of the management and outcomes of patients with Type 2 diabetes during Ramadan in 2010 (CREED).

AIM: To describe the characteristics and management of patients with diabetes who chose to fast during Ramadan in 2010. METHODS: This was a multi-country, retrospective, observational study, supplemented with physician and patient questionnaires, with data captured before, during and after Ramadan. A total of 508 physicians in 13 countries enrolled 3777 patients and a total of 3394 evaluable cases were analysed. We report on the subset of patients with Type 2 diabetes, which included 3250 patients (95.8%). RESULTS: Oral anti-hyperglycaemic therapy was the predominant pre-Ramadan therapy for most patients (76.6%). The treatment regimen was modified before Ramadan for 39.3% of all patients (34.9% for patients on oral drugs alone, 47.1% for patients on injectable drugs alone). Almost all physicians (96.2%) reported providing fasting-specific advice to patients and 62.6% report using guidelines or recommendations for the management of diabetes during Ramadan. In all, 64% of patients reported fasting everyday of Ramadan and 94.2% fasted for at least 15 days. CONCLUSIONS: Physicians have increasingly adopted multiple approaches to the management of fasting during Ramadan, including the adoption of international and/or national guidelines, providing fasting-specific advice and adjusting treatment regimens, such that patients are able to fast for a greater number of days without acute complications. Additional research is needed to explore physician and patient beliefs and practices to inform the evidence-based management of diabetes while fasting, both during and outside of Ramadan, and to identify and address barriers to the universal uptake of techniques to facilitate that management.

Estimated glomerular filtration rate progression in UK primary care patients with type 2 diabetes and diabetic kidney disease: a retrospective cohort study.

AIMS: To examine the rates of diabetic kidney disease (DKD) progression and associated factors, we undertook a study of estimated glomerular filtration rate (eGFR) in a historical cohort of UK primary care patients with type 2 diabetes mellitus (T2DM) and associated DKD from the Clinical Practice Research Datalink. METHODS: Our eligible population were patients with definitive T2DM from a recorded diagnostic code with either a diagnosis of chronic kidney disease (CKD) or renal function test values and renal abnormalities consistent with a CKD diagnosis, identified between 1 October 2006 and 31 December 2011. Only patients with albuminuria results reported in mg/l were used for the longitudinal statistical analyses of the eGFR rate of change using multilevel models. RESULTS: We identified 111,030 patients with T2DM. Among them 58.6% (95% confidence interval (CI): 58.3-58.9) had CKD and 37.2% (95% CI: 36.9-37.5%) had presumed DKD at baseline. Only 19.4% of patients had urinary albumin test results expressed as mg/l in the year prior to index date. Almost two-thirds (63.8%) of patients with T2DM and presumed DKD received prescriptions for angiotensin-converting enzyme (ACE) inhibitors or angiotensin type 1 receptor blockers (ARB) or both. Time-dependent variables that predict subsequent eGFR decline include increased albuminuria, time from index date and older age. CONCLUSION: Only a minority of diabetic patients with DKD had quantitative albuminuria assessments. The relatively low proportion of DKD patients with ACEi or ARB prescriptions suggests a gap between healthcare practice and available scientific evidence during the study period. Increased albuminuria and older age were the most consistent predictors of subsequent eGFR decline.

Monitoring meticillin resistant Staphylococcus aureus and its spread in Copenhagen, Denmark, 2013, through routine whole genome sequencing.

Typing of meticillin resistant Staphylococcus aureus (MRSA) by whole genome sequencing (WGS) is performed routinely in Copenhagen since January 2013. We describe the relatedness, based on WGS data and epidemiological data, of 341 MRSA isolates. These comprised all MRSA (n = 300) identified in Copenhagen in the first five months of 2013. Moreover, because MRSA of staphylococcal protein A (spa)-type 304 (t304), sequence type (ST) 6 had been associated with a continuous neonatal ward outbreak in Copenhagen starting in 2011, 41 t304 isolates collected in the city between 2010 and 2012 were also included. Isolates from 2013 found to be of t304, ST6 (n=14) were compared to the 41 earlier isolates. In the study, isolates of clonal complex (CC) 22 were examined in detail, as this CC has been shown to include the hospital-acquired epidemic MRSA (EMRSA-15) clone. Finally, all MRSA ST80 were also further analysed, as representatives of an important community-acquired MRSA in Europe. Overall the analysis identified 85 spa-types and 35 STs from 17 CCs. WGS confirmed the relatedness of epidemiologically linked t304 neonatal outbreak isolates. Several non-outbreak related patients had isolates closely related to the neonatal isolates suggesting unrecognised community chains of transmission and insufficient epidemiological data. Only four CC22 isolates were related to EMRSA-15. No community spread was observed among the 13 ST80 isolates. WGS successfully replaced conventional typing and added information to epidemiological surveillance. Creation of a MRSA database allows clustering of isolates based on single nucleotide polymorphism (SNP) calling and has improved our understanding of MRSA transmission.

Rates and risk of hospitalisation among patients with type 2 diabetes: retrospective cohort study using the UK General Practice Research Database linked to English Hospital Episode Statistics.

AIMS: To investigate the rates and risk of hospitalisations in patients with type 2 diabetes (T2D) mellitus in England. METHODS: This retrospective population-based cohort study used computerised records from the General Practice Research Database linked to Hospital Episode Statistics data in England. Patients with T2D from January 2006 to December 2010 were selected. Primary outcome measures were all-cause, non-diabetes-related, diabetes-related and hypoglycaemia-related hospitalisations. Factors associated with all-cause and diabetes-related hospitalisations were investigated with Cox's proportional hazards models. RESULTS: Amongst 97,689 patients with T2D, approximately 60% had at least one hospitalisation during the 4-year study period. Rates of hospitalisation were as follows: all-cause, 33.9 per 100 patient-years (pt-yrs); non-diabetes-related, 29.1 per 100 pt-yrs; diabetes-related, 18.8 per 100 pt-yrs and hypoglycaemia, 0.3 per 100 pt-yrs. The risk of all-cause hospitalisation increased with hospitalisation in the previous year, insulin use and the presence of major comorbidities. The risk of a diabetes-related hospitalisation increased with age, female gender, insulin use, chronic renal insufficiency, hypoglycaemia (as diagnosed by a general practitioner) and diabetes-related hospitalisation in the previous year. CONCLUSIONS: Patients with T2D are hospitalised at a considerably high rate for causes directly related with diabetes complications and stay longer in hospital. History of hospitalisation and complications of diabetes were found to be predictive of inpatient hospitalisations suggesting previous hospitalisation episodes could serve as points of intervention. This study highlights important areas for healthcare intervention and provides a reminder for vigilance when risk factors for hospitalisation in patients with T2D are present.

Clinical significance of disseminated tumour cells in non-small cell lung cancer.

BACKGROUND: Early-stage non-small cell lung cancer (NSCLC) patients have a high risk of disease relapse despite curatively intended surgical resection, and the detection of tumour cells in the bone marrow could be one method of determining the presence of the disseminated disease in its early stages. METHODS: Bone marrow aspirates were collected from 296 patients at the time of surgery, and the presence of disseminated tumour cells was determined with the help of immunomagnetic selection (IMS) using the MOC31-antibody recognising EpCAM and with the help of standard immunocytochemistry (ICC) using the anti-cytokeratin (CK) antibodies AE1/AE3. RESULTS: Disseminated tumour cells were found in 152 of 252 (59%) bone marrow samples using IMS and in 25 of 234 (11%) samples using ICC. No association between the two detection methods was observed. The presence of EpCAM⁺ cells was not associated with any clinicopathological parameters, whereas a higher frequency of CK⁺ cells was found in patients with an advanced pT status. Disseminated tumour cells, as detected using IMS, had no prognostic impact. Patients with CK⁺ cells in the bone marrow had a reduced relapse-free survival, but the difference was not statistically significant. CONCLUSION: Our findings do not support the further development of DTC detection for clinical use in early-stage NSCLC. Future studies should include the molecular characterisation of DTCs, along with an attempt to identify subpopulations of cells with biological and clinical significance.

A network meta-analysis to compare glycaemic control in patients with type 2 diabetes treated with exenatide once weekly or liraglutide once daily in comparison with insulin glargine, exenatide twice daily or placebo.

AIMS: The glucagon-like peptide-1 receptor agonists (GLP-1 RAs) exenatide once weekly (ExQW) and liraglutide once daily (QD) are indicated to improve glycaemic control in patients with type 2 diabetes. Although glycaemic control with ExQW versus liraglutide QD 1.8 mg has been directly compared, no studies have compared ExQW with liraglutide QD 1.2 mg or determined the probable relative efficacies of various injectable therapies for glycaemic control; therefore, a network meta-analysis was performed to address these questions. METHODS: A systematic review identified randomized controlled trials of ≥24 weeks that compared ExQW, liraglutide QD (1.2 mg, 1.8 mg), insulin glargine, exenatide twice daily (ExBID), or placebo. Twenty-two studies evaluating 11 049 patients were included in the network meta-analysis. Mean differences in HbA1c relative to placebo or each other and probability rankings were estimated. RESULTS: Estimated mean differences in HbA1c versus placebo were -1.15% (95% CrI: -1.31 to -1.00) for ExQW, -1.01% (95% CrI: -1.18 to -0.85) for liraglutide 1.2 mg, and -1.18% (95% CrI: -1.32 to -1.04) for liraglutide 1.8 mg. HbA1c differences for ExQW versus liraglutide 1.2 mg and 1.8 mg were -0.14% (95% CrI: -0.34 to 0.06) and 0.03% (95% CrI: -0.14 to 0.18), respectively. The estimated mean difference in HbA1c between liraglutide 1.2 mg and 1.8 mg was 0.17% (95% CrI: 0.02-0.30). Results were consistent when adjusted for background antihyperglycaemic medications and diabetes duration. CONCLUSIONS: This network meta-analysis did not identify meaningful differences in HbA1c lowering between ExQW and both liraglutide doses, suggesting that these GLP-1 RAs have similar glycaemic effects.

Preferences for medication attributes among patients with type 2 diabetes mellitus in the UK.

AIM: To examine preferences for oral medication attributes among participants with early and advanced type 2 diabetes mellitus (T2DM) in the UK using a discrete choice experiment (DCE). METHODS: A web-based DCE was administered where participants indicated which medication they preferred from two different hypothetical oral anti-diabetic (OAD) medication profiles, each composed of differing levels of seven attributes (efficacy, hypoglycaemic events, weight change, gastrointestinal/nausea side effects, urinary tract infection and genital infection, blood pressure and cardiovascular risk) for 20 sets of pair-wise comparisons. A random effects multinomial logit regression model was used to estimate the preference weight (PW) for each of the attribute levels, and the relative importance (RI) of each attribute was calculated. Analyses were conducted for the overall sample and for medication and gender subgroups. RESULTS: The final sample included 100 participants with a mean age of 62.9 (SD 11.1) years and comparable numbers of participants of each gender (51% male, 49% female). The majority of the participants were White-British (92%). The total PW and corresponding RI were highest for four of the seven attributes: hypoglycaemic events (PW = 1.98; RI = 24.7%), weight change (PW = 1.65; RI = 20.6%), gastrointestinal/nausea side effects (PW = 1.49; RI = 18.6%) and efficacy (PW = 1.44; RI = 18.0%). The RI values differed for some attributes across gender and number of current T2DM medication subgroups. CONCLUSION: The results suggest that hypoglycaemia, weight change, gastrointestinal side effects and efficacy are of primary importance to patients in their OAD preferences in T2DM. These four attributes comprised over 80% of the RI.

Development of a disease-specific version of the EQ-5D-5L for use in patients suffering from psoriasis: lessons learned from a feasibility study in the UK.

OBJECTIVES: The EuroQol five-dimensional (EQ-5D) questionnaire is a generic measure widely used for the assessment of health status. Research has suggested that it may be insensitive to the burdens associated with particular conditions. This study was designed to explore the feasibility of developing and valuing a disease-specific "bolt-on" version of the EQ-5D questionnaire for use in psoriasis. METHODS: A series of steps were undertaken to develop, test, and evaluate dimensions for a psoriasis-specific version of the EQ-5D questionnaire (hereafter referred to as the EQ-PSO questionnaire). Candidate dimensions were explored through a review of published literature, in-depth qualitative interviews with patients, and consultation with a clinical expert. A psychometric validation exercise was then undertaken to establish how well dimensions functioned. Two dimensions were selected for inclusion in a draft measure alongside the existing EQ-5D questionnaire dimensions: "skin irritation" and "self-confidence." Last, a time trade-off valuation exercise was conducted with 300 members of the UK general public to derive utilities for health states described by the measure. RESULTS: The psychometric analyses indicated that the two new candidate dimensions captured additional variance over and above the existing five dimensions. Data from the valuation exercise were analyzed by using different models. A collapsed random effects model was put forward as a parsimonious and accurate approach. Based on this model, estimated utilities ranged from 0.98 ± 0.02 for state "1111111" to 0.03 ± 0.29 for state "5555555." CONCLUSIONS: This study has developed the EQ-PSO questionnaire to support future psoriasis research and has informed the development of future bolt-on versions of the EQ-5D questionnaire.

Accumulated dose implications from systematic dose-rate transients in gated treatments with Viewray MRIdian accelerators.

The combination of magnetic resonance (MR) imaging and linear accelerators (linacs) into MR-Linacs enables continuous MR imaging and advanced gated treatments of patients. Previously, a dose-rate transient (∼8% reduced dose rate during the initial 0.5 s of each beam) was identified for a Viewray MRIdian MR-Linac (Klavsenet al2022Radiation Measurement106759). Here, the dose-rate transient is studied in more detail at four linacs of the same type at different hospitals. The implications of dose-rate transients were examined for gated treatments. The dose-rate transients were investigated using dose-per pulse measurements with organic plastic scintillators in three experiments: (i) A gated treatment with the scintillator placed in a moving target in a dynamic phantom, (ii) a gated treatment with the same dynamic conditions but with the scintillator placed in a stationary target, and (iii) measurements in a water-equivalent material to examine beam quality deviations at a dose-per-pulse basis. Gated treatments (i) compared with non-gated treatments with a static target in the same setup showed a broadening of accumulated dose profiles due to motion (dose smearing). The linac with the largest dose-rate transient had a reduced accumulated dose of up to (3.1 ± 0.65) % in the center of the PTV due to the combined dose smearing and dose-rate transient effect. Dose-rate transients were found to vary between different machines. Two MR-Linacs showed initial dose-rate transients that could not be identified from conventional linearity tests. The source of the transients includes an initial change in photon fluence rate and an initial change in x-ray beam quality. For gated treatments, this caused a reduction of more than 1% dose delivered at the central part of the beam for the studied, cyclic-motion treatment plan. Quality assurance of this effect should be considered when gated treatment with the Viewray MRIdian is implemented clinically.