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Standard of care for lower-grade glioma (LGG) is maximal safe resection and risk-adaptive adjuvant therapy. While patients who benefit the most from adjuvant chemotherapy have been elucidated in prospective randomized studies, comparable insights for adjuvant radiotherapy (RT) are lacking. We sought to identify and validate patterns of gene expression that are associated with differential outcomes among LGG patients treated by RT from two large genomics databases.Patients from The Cancer Genome Atlas (TCGA) with LGG (WHO grade II-III glioma) treated by surgery and adjuvant RT were randomized 1:1 to a discovery cohort or an internal validation cohort. Using the discovery cohort only, associations between tumor RNA-seq expression and progression-free survival (PFS) as well as overall survival (OS) were evaluated with adjustment for clinicopathologic covariates. A Genomic Risk Score (GRS) was then constructed from the expression levels of top genes also screened for involvement in glioma carcinogenesis. The prognostic value of GRS was further assessed in the internal validation cohort of TCGA and a second distinct database, compiled by the Chinese Glioma Genome Association (CGGA).From TCGA, 289 patients with LGG received adjuvant RT alone (38 grade II, 30 grade III) or chemoradiotherapy (CRT) (51 grade II, 170 grade III) between 2009 and 2015. From CGGA, 178 patients with LGG received adjuvant RT alone (40 grade II, 13 grade III) or CRT (41 grade II, 84 grade III) between 2004 and 2016. The genes comprising GRS are involved in MAP kinase activity, T cell chemotaxis, and cell cycle transition: MAP3K15, MAPK10, CCL3, CCL4, and ADAMTS1. High GRS, defined as having a GRS in the top third, was significantly associated with poorer outcomes independent of age, sex, glioma histology, WHO grade, IDH mutation, 1p/19q co-deletion, and chemotherapy status in the discovery cohort (PFS HR 1.61, 95% CI 1.10-2.36, P = 0.014; OS HR 2.74, 95% CI 1.68-4.47, P 0.001). These findings were replicated in the internal validation cohort (PFS HR 1.58, 95% CI 1.05-2.37, P = 0.027; OS HR 1.84, 95% CI 1.13-3.00, P = 0.015) and the CGGA external validation cohort (OS HR 1.72, 95% CI 1.27-2.34, P 0.001). Association between GRS and outcomes was observed only among patients who underwent RT, in both TCGA and CGGA.This study successfully identified an expression signature of five genes that stratified outcomes among LGG patients who received adjuvant RT, with two rounds of validation leveraging independent genomics databases. Expression levels of the highlighted genes were associated with PFS and OS only among patients whose treatment included RT, but not among those with omission of RT, suggesting that expression of these genes may be predictive of radiation treatment response. While additional prospective studies are warranted, interrogation of these genes may be considered in the multidisciplinary management of LGG.

Purpose To develop a machine learning (ML) model based on radiomic features (RF) extracted from whole prostate gland magnetic resonance imaging (MRI) for prediction of tumour hypoxia pre-radiotherapy. Material and methods Consecutive patients with high-grade prostate cancer and pre-treatment MRI treated with radiotherapy between 01/12/2007 and 1/08/2013 at two cancer centres were included. Cancers were dichotomised as normoxic or hypoxic using a biopsy-based 32-gene hypoxia signature (Ragnum signature). Prostate segmentation was performed on axial T2-weighted (T2w) sequences using RayStation (v9.1). Histogram standardisation was applied prior to RF extraction. PyRadiomics (v3.0.1) was used to extract RFs for analysis. The cohort was split 80:20 into training and test sets. Six different ML classifiers for distinguishing hypoxia were trained and tuned using five different feature selection models and fivefold cross-validation with 20 repeats. The model with the highest mean validation area under the curve (AUC) receiver operating characteristic (ROC) curve was tested on the unseen set, and AUCs were compared via DeLong test with 95% confidence interval (CI). Results 195 patients were included with 97 (49.7%) having hypoxic tumours. The hypoxia prediction model with best performance was derived using ridge regression and had a test AUC of 0.69 (95% CI: 0.14). The test AUC for the clinical-only model was lower (0.57), but this was not statistically significant (p = 0.35). The five selected RFs included textural and wavelet-transformed features. Conclusion Whole prostate MRI-radiomics has the potential to non-invasively predict tumour hypoxia prior to radiotherapy which may be helpful for individualised treatment optimisation.

ImportanceSpine metastasis can be treated with high-dose radiation therapy with advanced delivery technology for long-term tumor and pain control.ObjectiveTo assess whether patient-reported pain relief was improved with stereotactic radiosurgery (SRS) as compared with conventional external beam radiotherapy (cEBRT) for patients with 1 to 3 sites of vertebral metastases.Design, Setting, and ParticipantsIn this randomized clinical trial, patients with 1 to 3 vertebral metastases were randomized 2:1 to the SRS or cEBRT groups. This NRG 0631 phase 3 study was performed as multi-institutional enrollment within NRG Oncology. Eligibility criteria included the following: (1) solitary vertebral metastasis, (2) 2 contiguous vertebral levels involved, or (3) maximum of 3 separate sites. Each site may involve up to 2 contiguous vertebral bodies. A total of 353 patients enrolled in the trial, and 339 patients were analyzed. This analysis includes data extracted on March 9, 2020.InterventionsPatients randomized to the SRS group were treated with a single dose of 16 or 18 Gy (to convert to rad, multiply by 100) given to the involved vertebral level(s) only, not including any additional spine levels. Patients assigned to cEBRT were treated with 8 Gy given to the involved vertebra plus 1 additional vertebra above and below.Main Outcomes and MeasuresThe primary end point was patient-reported pain response defined as at least a 3-point improvement on the Numerical Rating Pain Scale (NRPS) without worsening in pain at the secondary site(s) or the use of pain medication. Secondary end points included treatment-related toxic effects, quality of life, and long-term effects on vertebral bone and spinal cord.ResultsA total of 339 patients (mean [SD] age of SRS group vs cEBRT group, respectively, 61.9 [13.1] years vs 63.7 [11.9] years; 114 [54.5%] male in SRS group vs 70 [53.8%] male in cEBRT group) were analyzed. The baseline mean (SD) pain score at the index vertebra was 6.06 (2.61) in the SRS group and 5.88 (2.41) in the cEBRT group. The primary end point of pain response at 3 months favored cEBRT (41.3% for SRS vs 60.5% for cEBRT; difference, −19 percentage points; 95% CI, −32.9 to −5.5; 1-sided P = .99; 2-sided P = .01). Zubrod score (a measure of performance status ranging from 0 to 4, with 0 being fully functional and asymptomatic, and 4 being bedridden) was the significant factor influencing pain response. There were no differences in the proportion of acute or late adverse effects. Vertebral compression fracture at 24 months was 19.5% with SRS and 21.6% with cEBRT (P = .59). There were no spinal cord complications reported at 24 months.Conclusions and RelevanceIn this randomized clinical trial, superiority of SRS for the primary end point of patient-reported pain response at 3 months was not found, and there were no spinal cord complications at 2 years after SRS. This finding may inform further investigation of using spine radiosurgery in the setting of oligometastases, where durability of cancer control is essential.Trial RegistrationClinicalTrials.gov Identifier: NCT00922974

Research drives innovation, however, recently Clinical Radiology has been overwhelmed by increased clinical demand, workforce shortages and lack of funding/protected research time. The newly released 2023 radiology speciality application process gives research a lower priority compared to other domains such as audit which is concerning given the current lack of research culture within the speciality. It is vital for the future radiology workforce to engage with research and in order to fulfil the Royal College of Radiologist’s new curriculum aims of strengthening research within training, we must continue attracting the brightest and best candidates and ensure research remains a priority.

The CD8+ T-cell response is prognostic for survival outcomes in several tumor types. However, whether this extends to tumors in the brain, an organ with barriers to T cell entry, remains unclear. Here, we analyzed immune infiltration in 67 brain metastasis (BrM) and found high frequencies of PD1+ TCF1+ stem-like CD8+ T-cells and TCF1- effector-like cells. Importantly, the stem-like cells aggregate with antigen presenting cells in immune niches, and niches were prognostic for local disease control. Standard of care for BrM is resection followed by stereotactic radiosurgery (SRS), so to determine SRS’s impact on the BrM immune response, we examined 76 BrM treated with pre-operative SRS (pSRS). pSRS acutely reduced CD8+ T cells at 3 days. However, CD8+ T cells rebounded by day 6, driven by increased frequency of effector-like cells. This suggests that the immune response in BrM can be regenerated rapidly, likely by the local TCF1+ stem-like population.

Objective: This analysis of the MACAFI (multicentre audit of cholecystostomy and further interventions) data aims to assess the procedural technique and technical specifications related to percutaneous cholecystostomy (PC) insertion in patients with acute calculous cholecystitis (ACC). PC can be performed either with transperitoneal (TP) or a transhepatic (TH) approach. There is no clear evidence for the superiority of either technique. Methods: The data set included patients who underwent PC for ACC between first January 2019 and first January 2021. Data included patient demographics, imaging diagnosis, insertion technique, tube size, and outcomes including 6 month follow-up. Results: 1186 patients from 36 sites were identified through the MACAFI study with 913 patients having access route recorded. A transhepatic route was used in 572 [62.6%] compared to 308 TP [33.7%]. There was an increased rate of bleeding when using the TH route (2.6% vs 0.3%, p = 0.01) although other post-procedural complications (such as bile leak) were similar between the two groups. No significant difference was demonstrated in 30- or 90-day mortality (TH vs TP, 8.7vs 9.3%, p = 0.86 and 13.8vs 15.4%, p = 0.58, respectively). The readmission rate with recurrent cholecystitis was significantly greater in those with TH compared to TP approach (22.0% vs 14.9%, p = 0.01, respectively). Conclusion: The TP PC approach may be safer than TH, with lower bleeding complication rate and fewer readmissions. Advances in knowledge: A transperitoneal approach for cholecystostomy was associated with lower bleeding complication rate and lower rate of readmissions with recurrent cholecystitis compared to the transhepatic approach.

To assess the mortality, readmission rates, and practice variation of percutaneous cholecystostomy (PC) in patients with acute calculous cholecystitis in the United Kingdom (UK).A total of 1,186 consecutive patients (636 men [53.6%]; median age, 75 years; range, 24-102 years) who underwent PC for acute calculous cholecystitis between January 1, 2019, and December 31, 2020, were included from 36 UK hospitals. The exclusion criteria were diagnostic aspirations, absence of acute calculous cholecystitis, and age less than 16 years. The coronavirus disease 2019 (COVID-19) lockdown was declared on March 26, 2020, in the UK, which served to distinguish among groups.Most patients (66.3%) underwent PC as definitive treatment, whereas 31.3% underwent PC as a bridge to surgery. The overall 30-day readmission rate was 42.2% (500/1,186), and the 30-day mortality was 9.1% (108/1,186). Centers performing fewer than 30 PCs per year had higher 90-day mortality than those performing more than 60 (19.3% vs 11.0%, respectively; P = .006). A greater proportion of patients presented with complicated acute calculous cholecystitis during the COVID-19 pandemic compared to prior (49.9% vs 40.9%, respectively; P = .007), resulting in more PCs (61.3 vs 37.9 per month, respectively; P.001). More PCs were performed in tertiary hospitals than in district general hospitals (9 vs 3 per 100 beds, respectively; P.001), with a greater proportion performed as a bridge to surgery (50.5% vs 22.8%, respectively; P.001).The practice of PC is highly variable throughout the UK. The readmission rates are high, and there is significant correlation between mortality and PC case volume.

Radiology has an important role in the diagnosis, staging and treatment of lung cancer and can offer minimally invasive therapies for poor surgical candidates. Radiology is also important in the follow up of patients after treatment, the assessment of treatment complications and detection of recurrent disease. Understanding the normal post-operative and post-radiation appearances, and recognizing early and late complications is useful for all clinicians involved in the care of patients with cancer.

PURPOSE: We aimed to evaluate the effect on the radiation dose to the patient by reducing the tube current during the placement of the ablation needles (reduced dose group) compared with the patient doses delivered when scanning at the standard fully diagnostic level (full dose group) in computed tomography (CT)-guided percutaneous cryoablation. METHODS: We conducted a retrospective study of 103 patients undergoing cryoablation in a tertiary cancer center. Overall, 62 patients were scanned with standard exposure parameters (full dose group) set on a 64-slice multidetector CT scanner, while 41 patients were scanned on a reduced dose protocol. Dose levels were retrieved from the hospital picture and archiving communication system including the volumetric CT dose index (CTDIvol), total dose length product (DLP), length of cryoablation procedure, number of cryoablation needles and patient size. Wilcoxon Mann-Whitney (rank-sum) tests were used to compare the median DLP, CTDIvol and skin dose between the two groups. RESULTS: Median total DLP for the full dose group was 6025 mGy·cm (1909–13353 mGy·cm) compared with 3391 mGy·cm (1683–6820 mGy·cm) for the reduced dose group. The reduced dose group had a 44% reduction in total DLP and 42% reduction in total CTDIvol (p < 0.001). The estimated skin doses were 384 mGy for the full dose group and 224 mGy for the reduced dose group (42% reduction) (p < 0.001). At 12-month follow-up, the technical success for the full dose (n=62) was 97% with 2 patients requiring a further cryoablation treatment for residual tumor. The technical success for the reduced dose group (n=41) was 100%. CONCLUSION: CT dose reduction technique during image-guided cryoablation treatment of renal tumors can achieve significant radiation dose reduction whilst maintaining sufficient image quality.

To evaluate the clinical outcomes and aortic remodelling rates following thoracic endovascular aortic repair (TEVAR) for acute or subacute type B aortic dissection (TBAD) based on technique. All TEVARs for acute/subacute TBAD between 01/01/2008 and 01/06/2020 were included. TEVARS were grouped by technique (TEVAR only, PETTICOAT and STABILISE). Aortic remodelling was assessed at three aortic levels on follow-up CT. Thirty-day technical/clinical success rates, re-intervention rates and complications were recorded. A total of 29 patients were included. The median age was 55 years (31–82). The median duration from initial presentation to TEVAR was 7 days (0–84). Intra-procedural complications included one aortic rupture from balloon moulding in a STABILISE case. Thirty-day mortality, stroke, spinal cord ischaemia and visceral ischaemia were 3% (n = 1), 3% (n = 1), 3% (n = 1) and 3% (n = 1), respectively. (All occurred in acute TBAD.) Overall survival was 50.5 months (18–115). Median follow-up was 31 months (1–115). Six patients (21%) required re-intervention, with a median time of 5 months (5–46) from first TEVAR. Overall complete aortic remodelling rates were: 89% at the proximal descending thoracic aorta, 78% at the distal thoracic aorta and 50% at the infra-renal abdominal aorta. At the infra-renal aorta, the STABILISE group (n = 11) had a higher complete aortic remodelling rate (82%) compared to TEVAR alone (n = 12) (20%). Endovascular intervention for acute and subacute TBAD is safe with a high rate of technical success. STABILISE results in higher aortic remodelling at the infra-renal aorta (82%) compared to TEVAR alone (20%) but risks aortic rupture from balloon moulding.

Highlights • Muscle invasive bladder cancer with variant histology has worse outcomes. • Chemoradiation is associated with similar OS to surgery for variant histology. • Adenocarcinoma and SCC have worse OS associated with chemoRT compared to surgery., Purpose For muscle-invasive bladder cancer, bladder preserving chemoradiotherapy (BPCRT) has shown to be a viable alternative for patients with urothelial carcinoma (UCa). Traditionally bladder cancer with variant histology UCa or other tumors types involving the bladder have worse outcomes and BPCRT has been contraindicated. However, there is limited high level evidence for this recommendation. Materials/methods The National Cancer Database (NCDB) was queried for all patients with Bladder cancer treated from 2004 to 2015 restricted to clinical stage T2-4, N0, M0 who had variants of UCa or other tumors types involving the bladder (e.g. adenocarcinoma and squamous cell carcinoma). Only patients treated with definitive intent with either radical cystectomy or BPCRT after maximal transurethral tumor resection were analyzed. Propensity-score matching was used. Results 356 patients had BPCRT and 2093 patients had definitive surgery for muscle-invasive bladder cancer limited to variants of UCa and other tumors types involving the bladder. On multivariable analysis worse prognosis was associated with age >65 years old (HR 1.24, p = 0.004) and T4 disease (HR 1.90, p

With demand increasing each year for diagnostic imaging and imaging guided interventions, it is important for the radiology workforce to expand in line with need. National and international societies such as the European Society of Radiology have an important role to play in showcasing the diversity of radiology, and highlighting the key role radiologists have in patient care and clinical decision-making to attract the next generation of radiologists. Medical students are an important group to engage with early. Meaningful exposure of undergraduates to radiology with an integrated programme and clinical placements in radiology is essential. Elective courses and dedicated 1-year Bachelor or Masters imaging programmes provide medical students with an opportunity for more in-depth study of radiology practice. Undergraduate radiology societies improve opportunities for engagement and mentorship. Innovations in imaging such as augmented-reality simulation and artificial intelligence and image-guided intervention also offer exciting training opportunities. Through these opportunities, students can gain insight into the wide variety of career opportunities in radiology.

Liver transplantation continues to rise in frequency, with over 1,000 procedures performed in the UK in 2018. Complications are increasingly uncommon but when they occur, early recognition and intervention is vital to save grafts. Imaging after the perioperative period is often performed at patients' local hospitals meaning that all radiologists and sonographers need to have an understanding of how to assess a transplant liver. Part I of this series will focus on vascular complications, including the normal postoperative vascular anatomy following liver transplantation, normal post-transplantation vascular imaging findings and abnormal findings that may prompt further investigation. Vascular complications following liver transplantation will be illustrated using a collection of cases.

Introduction The coronavirus disease 2019 (COVID-19) has created unprecedented challenges on the healthcare system. The aim of this multi-centre study was to measure the impact of COVID-19 on IR services in the UK. Material and Methods Retrospective cross-sectional study of IR practice in six UK centres during the COVID-19 pandemic was carried out. All therapeutic IR procedures were identified using the respective hospital radiology information systems and COVID-19 status found on the hospital patient record systems. The total number of therapeutic IR procedures was recorded over two time periods, 25/03/2019–21/04/2019 (control group) and 30/03/2020–26/04/2020 (COVID-19 group). The data points collected were: procedure type, aerosol-generating nature, acute or elective case, modality used, in- or out-of-hours case and whether the procedure was done at the bedside (portable). Results A 31% decrease in overall number of IR procedures was observed during COVID-19 compared to the control group (1363 cases vs 942 cases); however, the acute work decreased by only 0.5%. An increase in out-of-hours work by 10% was observed. COVID-19 was suspected or laboratory proved in 9.9% of cases (n = 93), and 15% of total cases (n = 141) were classed as aerosol-generating procedures. A 66% rise in cholecystostomy was noted during COVID-19. Image-guided ablation, IVC filters, aortic stent grafting and visceral vascular stenting had the greatest % decreases in practice during COVID-19, with 91.7%, 83.3%, 80.8% and 80.2% decreases, respectively. Conclusion During the global pandemic, IR has continued to provide emergency and elective treatment highlighting the adaptability of IR in supporting other specialties.

Background The interventional radiology (IR) trainee recruitment in the UK is lagging behind the pace of service expansion and is potentially hindered by underrepresented undergraduate curricula. Understanding the contributing factors that encourage junior doctors and medical students to consider an IR career will help the IR community to better focus the efforts on recruiting and nurturing the next generation. Methods Anonymised questionnaires on undergraduate and postgraduate IR exposure were distributed to attendees of five UK IR symposia between 2019 and 2020. Results 220 responses were received from 103 (47%) junior doctors and 117 (53%) medical students. Prior IR exposure strongly correlates with individuals’ positive views towards an IR career (Pearson’s R = 0.40, p < 0.001), with involvement in clinical activities as the most important independent contributor (OR 3.6, 95%CI 1.21–10.50, p = 0.021). Longer time spent in IR (especially as elective modules) and IR-related portfolio-building experiences (such as participating in research, attending conferences and obtaining career guidance) demonstrate strong association with willingness to pursue an IR career for the more motivated (p values < 0.05). The symposia had overall positive effects on subjective likelihood to pursue an IR career, particularly among junior doctors who face near-term career choices (p < 0.001). Conclusion Our study, focusing on a self-selected cohort, identified contributing factors to individuals’ willingness to pursue an IR career. Symposia have additional recruitment effects in extra-curricular settings. Active engagement with junior doctors and medical students through clinical activities and non-clinical portfolio-related experiences are key to generate informed and motivated candidates for the future of IR. Electronic supplementary material The online version of this article (10.1007/s00270-020-02655-7) contains supplementary material, which is available to authorised users.

Introduction To evaluate the long-term outcome of image-guided radiofrequency ablation (RFA) when treating histologically confirmed colorectal lung metastasis in terms of overall survival (OS), progression-free survival (PFS) and local tumour control (LTC). Materials and Methods Retrospective single-centre study. Consecutive RFA treatments of histologically proven lung colorectal metastases between 01/01/2008 and 31/12/14. The primary outcome was patient survival (OS and PFS). Secondary outcomes were local tumour progression (LTP) and complications. Prognostic factors associated with OS/ PFS were determined by univariate and multivariate analyses. Results Sixty patients (39 males: 21 females; median age 69 years) and 125 colorectal lung metastases were treated. Eighty percent (n = 48) also underwent lung surgery for lung metastases. Mean metastasis size (cm) was 1.4 ± 0.6 (range 0.3–4.0). Median number of RFA sessions was 1 (1–4). During follow-up (median 45.5 months), 45 patients died (75%). The estimated OS and PFS survival rates at 1, 3, 5, 7, 9 years were 96.7%, 74.7%, 44.1%, 27.5%, 16.3% (median OS, 52 months) and 66.7%, 31.2%, 25.9%, 21.2% and 5.9% (median PFS, 19 months). The LTC rate was 90% with 6 patients developing LTP with 1-, 2-, 3- and 4-year LTP rates of 3.3%, 8.3%, 10.0% and 10.0%. Progression-free interval P = 0.002, HR = 0.375) and total number of pulmonary metastases (≥ 3) treated (P = 0.037, HR = 0.480) were independent negative prognostic factors. Thirty-day mortality rate was 0% with no intra-procedural deaths. Conclusion The long-term OS and PFS following RFA for the treatment of histologically confirmed colorectal lung metastases demonstrate comparable oncological durability to surgery.

Radiation therapy to treat cancer has evolved significantly since the discovery of x-rays. Yet, radiation therapy still has room for improvement in reducing side effects and improving control of cancer. Safer and more effective delivery of radiation has led us to novel techniques and use of biomaterials. Biomaterials in combination with radiation and chemotherapy have started to appear in pre-clinical explorations and clinical applications, with many more on the horizon. Biomaterials have revolutionized the field of diagnostic imaging, and now are being cultivated into the field of theranostics, combination therapy, and tissue protection. This review summarizes recent development of biomaterials in radiation therapy in several application areas., Graphical abstract Image 1

Prospective studies have demonstrated increased local control with the addition of a radiosurgery (SRS) boost to whole-brain irradiation (WBRT) in patients with brain metastases. However, the clinical application of SRS boost can be limited by several factors, including tumor size, numbers of lesions, and high cost of care. Here, we investigate the use of WBRT with a simultaneous integrated boost (SIB) to visible lesions in patients with brain metastases. From 2011 to 2016, patients were prospectively enrolled and prescribed a dose of 25 or 37.5 Gray (Gy) WBRT with a SIB dose of 45 or 52.5 Gy to the gross lesions in 10 or 15 fractions, respectively. All plans were optimized for dose coverage of the whole brain and lesions using volumetric arc therapy (VMAT). Comprehensive neurocognitive and quality of life assessments were conducted at baseline and at follow-up. Thirteen patients were treated on this protocol. The 1-year local control rates were 92% at the patient level, and 98.6% at the lesion level. The overall 1-year intracranial control was 46%. Patients had no significant declines in Mini-Mental State Examination (MMSE), Hopkins Verbal Learning Test-Revised (HVLT-R), and Medical Outcomes Study (MOS) Cognitive Functional status scores pre- and post-treatment. WBRT with SIB to gross lesions using VMAT planning appears to be safe and effective in the treatment of brain metastases without significant cognitive decline. This treatment strategy should be considered in those patients with a high number of metastases or ones not amenable for radiosurgery. NCT01218542

Background Glioblastomas (GBMs) are aggressive brain tumors despite radiation therapy (RT) to 60 Gy and temozolomide (TMZ). Spectroscopic magnetic resonance imaging (sMRI), which measures levels of specific brain metabolites, can delineate regions at high risk for GBM recurrence not visualized on contrast-enhanced (CE) MRI. We conducted a clinical trial to assess the feasibility, safety, and efficacy of sMRI-guided RT dose escalation to 75 Gy for newly diagnosed GBMs. Methods Our pilot trial (NCT03137888) enrolled patients at 3 institutions (Emory University, University of Miami, Johns Hopkins University) from September 2017 to June 2019. For RT, standard tumor volumes based on T2-FLAIR and T1w-CE MRIs with margins were treated in 30 fractions to 50.1 and 60 Gy, respectively. An additional high-risk volume based on residual CE tumor and Cho/NAA (on sMRI) ≥2× normal was treated to 75 Gy. Survival curves were generated by the Kaplan–Meier method. Toxicities were assessed according to CTCAE v4.0. Results Thirty patients were treated in the study. The median age was 59 years. 30% were MGMT promoter hypermethylated; 7% harbored IDH1 mutation. With a median follow-up of 21.4 months for censored patients, median overall survival (OS) and progression-free survival were 23.0 and 16.6 months, respectively. This regimen appeared well-tolerated with 70% of grade 3 or greater toxicity ascribed to TMZ and 23% occurring at least 1 year after RT. Conclusion Dose-escalated RT to 75 Gy guided by sMRI appears feasible and safe for patients with newly diagnosed GBMs. OS outcome is promising and warrants additional testing. Based on these results, a randomized phase II trial is in development.

Simple Summary Ablation techniques use extremely hot or cold temperatures to kill small cancers. It is now known that in addition to killing the cancer cells, the ablation treatment may stimulate an immune response in patients against the cancer cells, acting like a vaccine. As a result, there is now interest in combining ablation together with drugs that target the immune system of patients with cancer to enhance the effects of both treatments. In order to develop such combined treatments and test them in clinical trials, we need to understand more about their effects so trials can be optimally designed to be most effective. We have analysed 164 circulating proteins in the blood from patients with small renal tumours undergoing ablation treatment to understand more about the effects of ablation on the patient, both at the level of the effects on the cancer cells and the response of the patients. Abstract Further biological understanding of the immune and inflammatory responses following ablation is critical to the rational development of combination ablation-immunotherapies. Our pilot exploratory study evaluated the circulating plasma protein profiles after image-guided ablation (IGA) of small renal masses to determine the resultant systemic effects and provide insight into impact both on the tumour and immune system. Patients undergoing cryotherapy (CRYO), radiofrequency ablation (RFA) or microwave ablation (MWA) for small renal tumours were recruited. Blood samples were obtained at four timepoints; two baselines prior to IGA and at 24 h and 1–3 months post-IGA, and a panel of 164 proteins measured. Of 55 patients recruited, 35 underwent ablation (25 CRYO, 8 RFA, 2 MWA) and biomarker measurements. The most marked changes were 24 h post-CRYO, with 29 proteins increasing and 18 decreasing significantly, principally cytokines and proteins involved in regulating inflammation, danger-associated molecular patterns (DAMPs), cell proliferation, hypoxic response, apoptosis and migration. Intra-individual variation was low but inter-individual variation was apparent, for example all patients showed increases in IL-6 (1.7 to 29-fold) but only 50% in CD27. Functional annotation analysis highlighted immune/inflammation and cell proliferation/angiogenesis-related clusters, with interaction networks around IL-6, IL-10, VEGF-A and several chemokines. Increases in IL-8, IL-6, and CCL23 correlated with cryoprobe number (p = 0.01, rs = 0.546; p = 0.009, rs = 0.5515; p = 0.005, rs = 0.5873, respectively). This initial data provide further insights into ablation-induced biological changes of relevance in informing trial design of immunotherapies combined with ablation.

Treatment for recurrent intracranial neoplasms is often difficult and less standardized. Since its approval by the Food & Drug Administration (FDA), GammaTileTM (GT, GT Medical Technologies, Tempe, AZ), a novel collagen tile cesium brachytherapy, has been investigated for use in this population. This study presents the initial experience with the use of GT for patients with recurrent intracranial neoplasms at a tertiary referral center. A retrospective analysis of all patients with GT implantation from November 2019 to July 2021 was performed. Information regarding demographics, clinical history, imaging data, prior tumor treatment, dosing, surgical complications, and outcomes was collected. Twelve patients were included in this study. Pathologies included gliomas (five patients), meningiomas (five patients), and metastatic tumors (two patients). The median tumor volume treated was 24 cc (IQR: 21.2 - 31.3 cc), and patients had a median of 7.5 tiles implanted (IQR: 5.4 - 10.3). One patient had a delayed epidural hematoma requiring reoperation, which was unrelated to GT implantation. Median follow-up was seven months (IQR: 3 -10), with the longest follow-up time of 20 months. Two patients have had local disease recurrence and three patients have had systemic progression of their disease. Three patients are deceased with survivals of 2.9, 4.8, and 5.8 months. Collagen tile brachytherapy is a safe and viable option for patients with recurrent intracranial tumors. Our data are consistent with early results seen at other institutions. Long-term data with larger patient populations are required to assess efficacy, safety, and indications for the use of this novel technology.

IntroductionRadiotherapy is the most common curative treatment for non-metastatic prostate cancer; however, up to 13% of patients will develop local recurrence within 10 years. Patients can undergo further and potentially curative treatment including salvage surgery, brachytherapy (BT), external beam radiotherapy, high-intensity focused ultrasound and cryotherapy. Systematic review shows that high-dose-rate (HDR) BT and stereotactic body radiotherapy (SBRT) have the best outcomes in terms of biochemical control and lowest side effects. The reirradiation options for previously irradiated prostate cancer (RO-PIP) trial aims to determine the feasibility of recruitment to a trial randomising patients to salvage HDR-BT or SBRT and provide prospective data on patient recorded toxicity outcomes that will inform a future phase III trial.Methods and analysisThe primary endpoint of the RO-PIP feasibility study is to evaluate the patient recruitment potential over 2 years to a trial randomising to either SBRT or HDR-BT for patients who develop local recurrence of prostate cancer following previous radiation therapy. The aim is to recruit 60 patients across 3 sites over 2 years and randomise 1:1 to SBRT or HDR-BT. Secondary objectives include recording clinician and patient-reported outcome measures to evaluate treatment-related toxicity. In addition, the study aims to identify potential imaging, genomic and proteomic biomarkers that are predictive of toxicity and outcome based on hypoxia status, a prognostic marker of prostate cancer.Ethics and disseminationThis study has been approved by the Yorkshire and The Humber—Bradford Leeds Research Ethics Committee (Reference: 21/YH/0305, IRAS: 297060, January 2022). The results will be presented in national and international conferences, published in peer-reviewed journals and will be communicated to relevant stakeholders. A plain English report will be shared with the study participants, patients’ organisations and media.Trial registration numberISRCTN 12238218 (Amy Ackroyd NIHR CPMS Team).

Objectives: Cone beam computed tomography (CBCT) is used for image guidance of stereotactic ablative radiotherapy (SABR), but it is susceptible to bowel motion artefacts. This trial evaluated the impact of hyoscine butylbromide (buscopan) on CBCT image quality and its feasibility within a radiotherapy workflow. Methods: A single-centre feasibility trial (ISRCTN24362767) was performed in patients treated with SABR for abdominal/pelvic oligorecurrence. Buscopan was administered to separate cohorts by intramuscular (IM) or intravenous (i.v.) injection on alternate fractions, providing within-patient control data. 4-point Likert scales were used to assess overall image quality (ranging from excellent to impossible to use) and bowel motion artefact (ranging from none to severe). Feasibility was determined by patient/radiographer questionnaires and toxicity assessment. Descriptive statistics are presented. Results: 16 patients were treated (8 by IM and 8 by i.v. buscopan). The percentage of images of excellent quality with/without buscopan was 47 vs 29% for IM buscopan and 65 vs 40% for i.v. buscopan. The percentage of images with no bowel motion artefact with/without buscopan was 24.6 vs 8.9% for IM buscopan and 25.8 vs 7% for i.v. buscopan. Four patients (25%) reported dry mouth. 14 patients (93%) would accept buscopan as routine. 11 radiographers (92%) reported no delay in treatments. Conclusions: A trend towards improved image quality/reduced bowel motion artefact was observed with IM/i.v. buscopan. Buscopan was well tolerated with limited impact on workflow. Advances in knowledge: This is the first trial of buscopan within a radiotherapy workflow. It demonstrated a trend to improved image quality and feasibility of use.

Objectives: To determine biopsy device failures, causative factors, complications and sample quality of the 16G end-cut Biopince™ and side-notch Bard™ needles. Methods: All ultrasound-guided non-targeted liver biopsies between 01/01/2016 and 31/12/2018 were included. Operator, device, number of failures, complications and repeat biopsies were recorded. Histopathology samples were reviewed for all cases of needle failure and a group with no failures, and graded “yes/no” for the presence of steatosis, inflammation and fibrosis. The pathology slides from these cases were reviewed to assess biopsy sample quality (length and portal tract number). The failure and no-failure groups were compared in terms of device type/histology, and sample quality was compared between the needle types. Results: 1004 patients were included. 93.8% (n = 942) required one needle pass to obtain a sample and 6.2% (n = 62) required >1 pass due to needle failure. Total of 76 needle failures, more with end-cut than side-notch needles (8.7% vs 2.9%) (p < 0.001). No needle failures resulted in complication. The presence of liver fibrosis was associated with fewer needle failures (p = 0.036). The major complication rate was 0.4% (4/1044). A biopsy with >10 portal tracts was obtained in 90.2% of specimens > 20 mm long, compared with 66% of 16–20 mm biopsies and 21% of 10 portal tracts was achieved in 10/26 (38.5%) of side-notch biopsies and 64/90 (71.1%) of end-cut biopsies (p = 0.004). Conclusion: Ultrasound-guided liver biopsy is safe and sample quality is consistently good when a core >20 mm long is obtained. The end-cut biopsy device generated reliably good quality biopsy samples; however, the needle failure rate was significantly higher than the side-cut needle. Advances in knowledge: Ultrasound-guided liver biopsy specimen quality is consistently good when a core >20 mm long is obtained which can be achieved with a single pass using the 16G BiopinceTM end-cut needle, although the needle failure rate is significantly higher than the 16G Max-Core™ Bard™ side-notch needle.

Summary Background The dependence of the adaptive immune system on circadian rhythm is an emerging field of study with potential therapeutic implications. We aimed to determine whether specific time-of-day patterns of immune checkpoint inhibitor infusions might alter melanoma treatment efficacy. Methods Melanoma Outcomes Following Immunotherapy (MEMOIR) is a longitudinal study of all patients with melanoma who received ipilimumab, nivolumab, or pembrolizumab, or a combination of these at a single tertiary cancer centre (Winship Cancer Institute of Emory University, Atlanta, GA, USA). For this analysis, we collected deidentified participant-level data from the MEMOIR database for adults (age ≥18 years) diagnosed with stage IV melanoma between 2012 and 2020. Those who received fewer than four infusions were excluded. Standard of care doses were used, with modifications at the treating physicians' discretion. The primary outcome was overall survival, defined as death from any cause and indexed from date of first infusion of immune checkpoint inhibitor. We calculated the association between overall survival and proportion of infusions of immune checkpoint inhibitors received after 1630 h (a composite time cutoff derived from seminal studies of the immune-circadian rhythm to represent onset of evening) using Cox regression and propensity score-matching on age, Eastern Cooperative Oncology Group performance status, serum lactate dehydrogenase concentration, and receipt of corticosteroids and radiotherapy. Treatment-related adverse events that led to change or discontinuation of immune checkpoint inhibitors were also assessed. Findings Between Jan 1, 2012, and Dec 31, 2020, 481 patients with melanoma received treatment with immune checkpoint inhibitors at the study centre, of whom 299 had stage IV disease and were included in this study; median follow-up was 27 months (IQR 14 to 47). In the complete unmatched sample, 102 (34%) patients were female and 197 (66%) were male, with a median age of 61 years (IQR 51 to 72). Every additional 20% of infusions of immune checkpoint inhibitors received after 1630 h (among all infusions received by a patient) conferred an overall survival hazard ratio (HR) of 1·31 (95% CI 1·00 to 1·71; p=0·046). A propensity score-matched analysis of patients who did (n=73) and did not (n=73) receive at least 20% of their infusions of immune checkpoint inhibitors after 1630 h (54 [37%] of 146 patients were women and 92 [63%] were men, with a median age of 58 years [IQR 48 to 68]) showed that having at least 20% of infusions in the evening was associated with shorter overall survival (median 4·8 years [95% CI 3·9 to not estimable] vs not reached; HR 2·04 [1·04 to 4·00; p=0·038]). This result remained robust to multivariable proportional hazards adjustment with (HR 1·80 [1·08 to 2·98; p=0·023]) and without (2·16 [1·10 to 4·25; p=0·025]) inclusion of the complete unmatched study sample. The most common adverse events were colitis (54 [18%] of 299 patients), hepatitis (27 [9%]), and hypophysitis (15 [5%]), and there were no treatment-related deaths. Interpretation Our findings are in line with an increasing body of evidence that adaptive immune responses are less robust when initially stimulated in the evening than if stimulated in the daytime. Although prospective studies of the timing of immune checkpoint inhibitor infusions are warranted, efforts towards scheduling infusions before mid-afternoon could be considered in the multidisciplinary management of advanced melanoma. Funding National Institutes of Health, American Society for Radiation Oncology and Melanoma Research Alliance, and Winship Cancer Institute.

Purpose Incidence of anal squamous cell carcinoma (ASCC) is increasing, with curative chemoradiotherapy (CRT) as the primary treatment of non-metastatic disease. A significant proportion of patients have locoregional treatment failure (LRF), but distant relapse is uncommon. Accurate prognostication of progression-free survival (PFS) would help personalisation of CRT regimens. The study aim was to evaluate novel imaging pre-treatment features, to prognosticate for PFS in ASCC. Methods Consecutive patients with ASCC treated with curative intent at a large tertiary referral centre who underwent pre-treatment FDG-PET/CT were included. Radiomic feature extraction was performed using LIFEx software on baseline FDG-PET/CT. Outcome data (PFS) was collated from electronic patient records. Elastic net regularisation and feature selection were used for logistic regression model generation on a randomly selected training cohort and applied to a validation cohort using TRIPOD guidelines. ROC-AUC analysis was used to compare performance of a regression model encompassing standard clinical prognostic factors (age, sex, tumour and nodal stage—model A), a radiomic feature model (model B) and a combined radiomic/clinical model (model C). Results A total of 189 patients were included in the study, with 145 in the training cohort and 44 in the validation cohort. Median follow-up was 35.1 and 37. 9 months, respectively for each cohort, with 70.3% and 68.2% reaching this time-point with PFS. GLCM entropy (a measure of randomness of distribution of co-occurring pixel grey-levels), NGLDM busyness (a measure of spatial frequency of changes in intensity between nearby voxels of different grey-level), minimum CT value (lowest HU within the lesion) and SMTV (a standardized version of MTV) were selected for inclusion in the prognostic model, alongside tumour and nodal stage. AUCs for performance of model A (clinical), B (radiomic) and C (radiomic/clinical) were 0.6355, 0.7403, 0.7412 in the training cohort and 0.6024, 0.6595, 0.7381 in the validation cohort. Conclusion Radiomic features extracted from pre-treatment FDG-PET/CT in patients with ASCC may provide better PFS prognosis than conventional staging parameters. With external validation, this might be useful to help personalise CRT regimens in the future. Electronic supplementary material The online version of this article (10.1007/s00259-019-04495-1) contains supplementary material, which is available to authorized users.

PURPOSE: Radical cystectomy currently remains the standard of care for muscle-invasive bladder cancer (MIBC). However, surgery can be associated with considerable morbidity and mortality, including the removal of the bladder. An alternative strategy is to preserve the bladder through concurrent chemo-radiation following a maximal trans-urethral resection of the tumor. National protocols using a bladder preservation approach have demonstrated disease-specific outcomes comparable to radical cystectomy in selected patients, but these results have not been replicated in previously reported population-based series. Here, we describe an outcomes analysis of patients with MIBC treated with either radical surgery or bladder-preserving chemo-radiation (BPCRT) for those patients meeting BPCRT criterion using the National Cancer Database (NCDB). METHODS AND MATERIALS: Using the NCDB, patients with AJCC clinical T2-3, N0, M0 urothelial carcinoma diagnosed between 2004–2013 were included for analysis. Only patients treated with definitive intent with either radical cystectomy or concurrent chemotherapy and radiation after a maximal transurethral tumor resection were included. Propensity-score matching was employed. RESULTS: Among 8,454 eligible patients, 7,276 (86%) underwent radical cystectomy, and 1,178 (14%) underwent BPCRT. Patients undergoing BPCRT were significantly older (median age 77 vs 68, p