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Background Prostate radiotherapy (RT) is a first-line option for newly diagnosed men with low-burden metastatic prostate cancer. The current criterion to define this clinical state is based on manual bone metastasis counts, but enumeration of bone metastases is limited by interobserver variations, and it does not account for metastasis volume or lesional coalescence. The automated bone scan index (aBSI) is a quantitative method of evaluating bone metastatic burden in a standardised and reproducible manner. Objective To evaluate whether aBSI has utility as a predictive imaging biomarker to define a newly diagnosed metastatic prostate cancer population that might benefit from the addition of prostate RT to standard of care (SOC) systemic therapy. Design, setting, and participants This is an exploratory analysis of men with newly diagnosed metastatic prostate cancer randomised in a 1:1 ratio to either SOC or SOC + prostate RT within the STAMPEDE “M1|RT comparison”. Intervention The SOC was lifelong androgen deprivation therapy, with up-front docetaxel permitted from December 2015. Men allocated RT received either a daily or a weekly schedule that was nominated before randomisation. Outcome measurements and statistical analysis Baseline bone scans were evaluated retrospectively to calculate aBSI. We used overall (OS) and failure-free (FFS) survival as the end points. Treatment-aBSI interaction was evaluated using the multivariable fractional polynomial interaction (MFPI) and subpopulation treatment effect pattern plot. Further analysis was done in aBSI quartiles using Cox regression models adjusted for stratification factors. Results and limitations : Baseline bone scans for 660 (SOC: 323 and SOC + RT: 337) of 2061 men randomised within the “M1|RT comparison” met the software requirements for aBSI calculation. The median age was 68 yr, median PSA was 100 ng/mL, median aBSI was 0.9, and median follow-up was 39 mo. Baseline patient characteristics including aBSI were balanced between the treatment groups. Using the MFPI procedure, there was evidence of aBSI-treatment interaction for OS (p = 0.04, MFPI procedure) and FFS (p, Take Home Message In this exploratory analysis of 660 men with newly diagnosed metastatic prostate cancer randomised within a clinical trial, a low automated bone scan index was found to be predictive of overall and failure-free survival benefit from the addition of prostate radiotherapy to standard of care systemic therapy. This was also observed with secondary clinical end points.

Background Abiraterone acetate received licencing for use in only "high-risk" metastatic hormone-naive prostate cancer (mHNPC) following the LATITUDE trial findings. However, a "risk"-related effect was not seen in the STAMPEDE trial. There remains uncertainty as to whether men with LATITUDE "low-risk" M1 disease benefit from androgen deprivation therapy (ADT) combined with abiraterone acetate and prednisolone (AAP). Objective Evaluation of heterogeneity of effect between LATITUDE high- and low-risk M1 prostate cancer patients receiving ADT + AAP in the STAMPEDE trial. Design, setting, and participants A post hoc subgroup analysis of the 2017 STAMPEDE "abiraterone comparison". Staging scans for M1 patients contemporaneously randomised to ADT or ADT + AAP within the STAMPEDE trial were evaluated centrally and blind to treatment assignment. Stratification was by risk according to the criteria set out in the LATITUDE trial. Exploratory subgroup stratification incorporated the CHAARTED criteria. Outcome measurements and statistical analysis The primary outcome measure was overall survival (OS) and the secondary outcome measure was failure-free survival (FFS). Further exploratory analysis evaluated clinical skeletal-related events, progression-free survival (PFS), and prostate cancer-specific death. Standard Cox-regression and Kaplan-Meier survival estimates were employed for analysis. Results and limitations A total of 901 M1 STAMPEDE patients were evaluated after exclusions. Of the patients, 428 (48%) were identified as having a low risk and 473 (52%) a high risk. Patients receiving ADT + AAP had significantly improved OS (low-risk hazard ratio [HR]: 0.66, 95% confidence interval or CI [0.44–0.98]) and FFS (low-risk HR: 0.24, 95% CI [0.17–0.33]) compared with ADT alone. Heterogeneity of effect was not seen between low- and high-risk groups for OS or FFS. For OS benefit in low risk, the number needed to treat was four times greater than that for high risk. However, this was not observed for the other measured endpoints. Conclusions Men with mHNPC gain treatment benefit from ADT + AAP irrespective of risk stratification for "risk" or "volume". Patient summary Coadministration of abiraterone acetate and prednisolone with androgen deprivation therapy (ADT) is associated with prolonged overall survival and disease control, compared with ADT alone, in all men with metastatic disease starting hormone therapy for the first time.

Purpose To evaluate the utility of Diffusion-weighted MRI in the differentiation of benign from malignant skeletal lesions of the pelvis. Materials and methods In this retrospective study 33 patients with indeterminate skeletal lesions of the pelvis were evaluated with DWI. Minimum, mean, maximum ADC-values of the skeletal lesions were measured followed by qualitative assessment of DWI. All patients underwent histological confirmation using CT-guided biopsy or surgical resection. The histology of the skeletal lesions was correlated with the findings on DWI. Results There were 13 malignant lesions and 20 benign lesions. The mean, minimum and maximum ADC values (×10–6mm2/s) for benign skeletal lesions was higher than the mean ADC-values for malignant lesions (1422.2 vs 1263.7; 780.4 vs 771.8; 1969.6 vs 1676.8 respectively). These differences were however not statistically significant (P-values = 0.29; 0.94; 0.149 respectively). The sensitivity, specificity, positive predictive value and negative predictive value for qualitative assessment of Diffusion-weighted MRI in the differentiation of benign from malignant skeletal lesions were: 53.9%, 85%, 70%, 73.9% respectively. Qualitative assessment of DWI (restricted diffusion versus non-restricted diffusion) allowed differentiation of benign from malignant skeletal lesions (P-value = 0.0259). Conclusions Qualitative assessment of DWI may aid in the differentiation of benign skeletal lesions from malignant skeletal lesions of the pelvis. Although DWI has a low sensitivity in the distinction of the two disease entities, it may be a useful adjunct due to its relatively high specificity. This is of particular importance in lymphoma where biopsy may only show chronic inflammatory cells and hence may be false negative.

Background STAMPEDE has previously reported that upfront docetaxel (Doc) improved overall survival (OS) for patients (pts) starting long-term androgen deprivation therapy (ADT). We report the long-term outcomes for M1 pts using OS as the primary outcome measure. We also assessed if benefit of Doc depended on metastatic burden, as suggested by previous trials, using the CHAARTED definition of high burden (HB) and low burden (LB) baseline disease. Methods 724 SOC and 362 SOC+Doc pts were recruited with a 2:1 randomised stratified allocation. Analysis used Cox regression models, adjusted for all stratification factors, with emphasis on restricted mean survival time if hazards were non-proportional. Retrospectively-collected imaging data, blinded to trial arm, was used to categorise pts as having LB or HB disease. Results Median follow-up was ∼6.5yr, compared to ∼3.5yr when last reported. There were 494 deaths on SOC (41% increase in deaths compared to previous report), with median OS=43.1 months (m). There was good evidence of benefit of SOC+Doc on OS (median = 59.1m, HR=0.81, 95% CI 0.69-0.95, P=0.009). Metastatic burden was assessable for 830/1086 (76%) pts; subgroups were representative of the full M1 cohort in terms of stratification factors. There was no evidence of heterogeneity of Doc effect between the LB and HB subgroups (interaction P=0.827; LB HR=0.76, 95%CI 0.54-1.07, P=0.107; HB HR=0.81, 95%CI 0.64-1.02, P=0.064). Analysis of other outcomes also found evidence of benefit of SOC+Doc over SOC in failure-free survival (FFS; HR=0.66, 95% CI 0.57-0.76, P Conclusions The clinically significant benefit in survival for upfront Doc persists after longer follow-up, with no evidence that the benefit differed dependent on disease burden. We advocate that upfront Doc is considered for both LB and HB M1 pts. Clinical trial identification NCT00268476. Legal entity responsible for the study University College London. Funding Cancer Research UK; Sanofi; MRC; Astellas; Clovis; Janssen; Novartis; Pfizer. Disclosure N.W. Clarke: Advisory / Consultancy: Janssen. G. Attard: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy, Travel / Accommodation / Expenses: Medivation; Advisory / Consultancy: Novartis; Advisory / Consultancy: Millennium Pharmaceuticals; Advisory / Consultancy, Travel / Accommodation / Expenses: Abbott Laboratories; Advisory / Consultancy, Travel / Accommodation / Expenses: Essa Pharmaceuticals; Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer Healthcare Pharmaceuticals; Speaker Bureau / Expert testimony: Takeda; Speaker Bureau / Expert testimony: Sanofi-Aventis; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Arno Therapeutics; Research grant / Funding (self): Innocrin Pharma; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Janssen; Advisory / Consultancy: Veridex; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses, Non-remunerated activity/ies: Roche/Ventana; Advisory / Consultancy, Non-remunerated activity/ies: Pfizer; Research grant / Funding (institution), I was an employee of the ICR, where abiraterone acetate was developed, up to 8 January 2018. The Institute of Cancer Research (ICR). S. Chowdhury: Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Janssen Pharmaceutical. D. Dearnaley: Research grant / Funding (institution), Financial Support for Trial Recruitment: UK National Institute for Health Research Clinical Research Network (NIHR CRN); Research grant / Funding (institution), My employer, The Institute of Cancer Research, receives a royalty income from abiraterone. I receive a share of this income through the ICR's Rewards to Discoverer's Scheme: The Institute of Cancer Research (ICR); Research grant / Funding (self): Cancer Research UK; Honoraria (self), Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy: Amgen; Advisory / Consultancy, Travel / Accommodation / Expenses: Sandoz; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen. S. Gillessen: Honoraria (institution): Bayer; Honoraria (institution): Curevac; Honoraria (institution), Advisory / Consultancy: Janssen; Honoraria (institution): Astellas; Honoraria (institution), Advisory / Consultancy: Orion; Advisory / Consultancy: MaxiVax SA; Honoraria (institution), Advisory / Consultancy: AAA; Honoraria (institution): Ferring; Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (institution): Innocrin Pharmaceuticals; Honoraria (institution), Advisory / Consultancy: Sanofi; Honoraria (institution): Novartis; Non-remunerated activity/ies: Nectar Therapeutics; Non-remunerated activity/ies: ProteoMedix; Honoraria (institution): Cell Search; Honoraria (institution): Clovis; Honoraria (institution): Bristol-Myers Squibb. R. Jones: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Non-remunerated activity/ies: Janssen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Astellas; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Sanofi; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis. Z. Malik: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Astellas; Travel / Accommodation / Expenses: Bayer. M.D. Mason: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer. C. Parker: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Bayer; Honoraria (self), Advisory / Consultancy: AAA; Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen. A.G. Omlin: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy: Roche; Advisory / Consultancy: MSD; Advisory / Consultancy: Molecular Partners; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen; Research grant / Funding (institution): Teva. M.R. Sydes: Research grant / Funding (self), Non-remunerated activity/ies, Unrestricted grant to contribute to STAMPEDE overall: Astellas; Research grant / Funding (self), Non-remunerated activity/ies, Unrestricted grant to contribute to STAMPEDE overall: Clovis Oncology; Research grant / Funding (self), Non-remunerated activity/ies, Unrestricted grant to contribute to STAMPEDE overall: Novartis; Research grant / Funding (self), Non-remunerated activity/ies, Unrestricted grant to contribute to STAMPEDE overall: Pfizer; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eli Lilly; Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses, Non-remunerated activity/ies, Unrestricted grant to contribute to STAMPEDE overall: Janssen; Research grant / Funding (self), Non-remunerated activity/ies, Unrestricted grant to contribute to STAMPEDE overall: Sanofi. M.K.B. Parmar: Research grant / Funding (self), Unrestricted grant to contribute to another comparison of STAMPEDE which supports the protocol overall, plus relevant drug and distribution.: Astellas; Research grant / Funding (self), Unrestricted grant to contribute to another comparison of STAMPEDE which supports the protocol overall, plus relevant drug and distribution.: Clovis Oncology; Research grant / Funding (self), Unrestricted grant to contribute to another comparison of STAMPEDE which supports the protocol overall, plus relevant drug and distribution.: Novartis; Research grant / Funding (self), Unrestricted grant to contribute to another comparison of STAMPEDE which supports the protocol overall, plus relevant drug and distribution.: Pfizer; Research grant / Funding (self), Unrestricted grant to contribute to another comparison of STAMPEDE which supports the protocol overall, plus relevant drug and distribution.: Sanofi. N.D. James: Advisory / Consultancy: Sanofi; Advisory / Consultancy: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Janssen. All other authors have declared no conflicts of interest.

We report a lesion–symptom mapping analysis of visual speech production deficits in a large group (280) of stroke patients at the sub-acute stage (, Highlights • The shared and unique neural substrates of object naming were examined in 280 stroke patients. • Clinical CT scans and performance on clinical language tests were analysed using voxel-based morphometry. • Principal component analysis on the test scores identified a shared language component and a unique naming component. • The general language component recruits a widespread left-lateralised fronto-temporal network. • The unique object naming component is linked to the bi-anterior temporal poles and cerebellar areas.

Background Prostate radiotherapy (PRT) with androgen deprivation therapy (ADT) is now recommended as a first line option for de-novo low burden metastatic prostate cancer. In the STAMPEDE “M1|RT comparison” metastatic burden was a determinant of benefit, based on pre-specified prognostic criteria. We have now performed exploratory analyses of metastases as defined by site and number to improve prediction of treatment benefit from PRT. Methods Patients (pts) randomized to the ADT (± docetaxel) vs PRT + ADT (± docetaxel) were studied. Metastatic site, distribution and number were evaluated based on conventional imaging and used to explore treatment effects to refine the metastatic burden definition. Results focused on the trial’s key outcome measures: overall (OS) & failure-free survival (FFS), analysed using standard survival analysis methods. HR Results Following exclusions (imaging unavailable for central review, n = 122), 1939 pts randomized in “M1|RT comparison” were included. Of these, 181 pts had only lymph node (LN) mets, 1587 had bone (±LN) mets and 171 had other visceral mets (±bone/LN). Baseline characteristics such as age (median 68 years), PSA (median 98 ng/ml) were balanced between the arms. In LN only pts, PRT improved OS (HR = 0.62, 95%CI 0.35-1.09) & FFS (HR = 0.64, 95%CI 0.43-0.96). In bone (±LN) pts with 0.1) for baseline factors such as age, N stage, Gleason score, RT schedule or docetaxel use. Conclusions Prostate RT + ADT (± docetaxel) improved OS & FFS in pts with only LN or Clinical trial identification NCT00268476. Legal entity responsible for the study Medical Research Council-Clinical Trials Unit and University of Manchester. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Aim To present the imaging features of post-traumatic heterotopic ossification (HO) of the distal tibiofibular syndesmosis initially suspected to be a surface osteosarcoma. Materials and methods A retrospective review was conducted of the presenting complaint and imaging features of patients with a final diagnosis of HO referred over an 8 year period to a specialist orthopaedic oncology centre. Results Five patients with HO were identified. All were adult males with an age range of 19–41 years. There was a history of prior ankle trauma in all cases but the significance was not recognized at the time of referral to the specialist centre. There was radiographic evidence of HO arising from the inner aspects of the distal tibia and fibula approximately 3 cm proximal to the ankle joint. The HO was “kissing” in two cases and partially fused (synostosis) in two. The HO in the fifth case was arising on the inner fibular cortex alone. Magnetic resonance imaging (MRI), available in four cases, showed predominantly low signal intensity due to the dense bone formation. Conclusion The history of prior ankle trauma with ossification arising from the inner aspects of both the distal tibia and fibula is typical of post-traumatic HO and distinguish this benign condition from the rare surface osteosarcoma at this site.

Pleomorphic xanthoastrocytoma is a very rare brain tumour accounting for only 1% of all brain neoplasms. It is however important to be familiar with the radiological findings of this tumour because it has a characteristic imaging appearance and is highly amenable to surgical resection with a good prognosis. We report two cases of pleomorphic xanthoastrocytomas, describe the neuroimaging findings, correlate the imaging findings with the histopathological findings and review the current literature.

Thymomas are rare tumours that are usually diagnosed in patients with myasthenia gravis or as an incidental finding. We describe a case of a thymoma mimicking pulmonary stenosis due to external compression of the pulmonary artery. To our knowledge this has only been described in two previous cases in the literature.