BackgroundRadiotherapy is an effective treatment of intermediate/high-risk locally advanced prostate cancer, however, >30% of patients relapse within 5 years. Clinicopathological parameters currently fail to identify patients prone to systemic relapse and those whom treatment intensification may be beneficial. The purpose of this study was to independently validate the performance of a 70-gene Metastatic Assay in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy.Patients and methodsA bridging cohort of prostate cancer diagnostic biopsy specimens was profiled to enable optimization of the Metastatic Assay threshold before further independent clinical validation in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy. Multivariable Cox proportional hazard regression analysis was used to assess assay performance in predicting biochemical failure-free survival (BFFS) and metastasis-free survival (MFS).ResultsGene expression analysis was carried out in 248 patients from the independent validation cohort and the Metastatic Assay applied. Ten-year MFS was 72% for Metastatic Assay positive patients and 94% for Metastatic Assay negative patients [HR = 3.21 (1.35–7.67); P = 0.003]. On multivariable analysis the Metastatic Assay remained predictive for development of distant metastases [HR = 2.71 (1.11–6.63); P = 0.030]. The assay retained independent prognostic performance for MFS when assessed with the Cancer of the Prostate Assessment Score (CAPRA) [HR = 3.23 (1.22–8.59); P = 0.019] whilst CAPRA itself was not significant [HR = 1.88, (0.52–6.77); P = 0.332]. A high concordance [100% (61.5–100)] for the assay result was noted between two separate foci taken from 11 tumours, whilst Gleason score had low concordance.ConclusionsThe Metastatic Assay demonstrated significant prognostic performance in patients treated with radical radiotherapy both alone and independent of standard clinical and pathological variables. The Metastatic Assay could have clinical utility when deciding upon treatment intensification in high-risk patients. Genomic and clinical data are available as a public resource.

ObjectiveCurrent strategies to guide selection of neoadjuvant therapy in oesophageal adenocarcinoma (OAC) are inadequate. We assessed the ability of a DNA damage immune response (DDIR) assay to predict response following neoadjuvant chemotherapy in OAC.DesignTranscriptional profiling of 273 formalin-fixed paraffin-embedded prechemotherapy endoscopic OAC biopsies was performed. All patients were treated with platinum-based neoadjuvant chemotherapy and resection between 2003 and 2014 at four centres in the Oesophageal Cancer Clinical and Molecular Stratification consortium. CD8 and programmed death ligand 1 (PD-L1) immunohistochemical staining was assessed in matched resection specimens from 126 cases. Kaplan-Meier and Cox proportional hazards regression analysis were applied according to DDIR status for recurrence-free survival (RFS) and overall survival (OS).ResultsA total of 66 OAC samples (24%) were DDIR positive with the remaining 207 samples (76%) being DDIR negative. DDIR assay positivity was associated with improved RFS (HR: 0.61; 95% CI 0.38 to 0.98; p=0.042) and OS (HR: 0.52; 95% CI 0.31 to 0.88; p=0.015) following multivariate analysis. DDIR-positive patients had a higher pathological response rate (p=0.033), lower nodal burden (p=0.026) and reduced circumferential margin involvement (p=0.007). No difference in OS was observed according to DDIR status in an independent surgery-alone dataset.DDIR-positive OAC tumours were also associated with the presence of CD8+ lymphocytes (intratumoural: p<0.001; stromal: p=0.026) as well as PD-L1 expression (intratumoural: p=0.047; stromal: p=0.025).ConclusionThe DDIR assay is strongly predictive of benefit from DNA-damaging neoadjuvant chemotherapy followed by surgical resection and is associated with a proinflammatory microenvironment in OAC.

The metastatic assay may improve the ability to detect patients at risk of metastatic recurrence following radical prostatectomy. The impact of adjuvant therapies should be assessed in this higher-risk population.

Backgroundinstitutionalisation following acute hospital admission is common and yet poorly described, with policy documents advising against this transition.Objectiveto characterise the individuals admitted to a care home on discharge from an acute hospital admission and to describe their assessment.Design and settinga retrospective cohort study of people admitted to a single large Scottish teaching hospital.Subjects100 individuals admitted to the acute hospital from home and discharged to a care home.Methodsa single researcher extracted data from ward-based case notes.Resultspeople discharged to care homes were predominantly female (62%), widowed (52%) older adults (mean 83.6 years) who lived alone (67%). About 95% had a diagnosed cognitive disorder or evidence of cognitive impairment. One-third of cases of delirium were unrecognised. Hospital stays were long (median 78.5 days; range 14–231 days) and transfers between settings were common. Family request, dementia, mobility, falls risk and behavioural concerns were the commonest reasons for the decision to admit to a care home. About 55% were in the acute hospital when the decision for a care home was made and 44% of that group were discharged directly from the acute hospital.Conclusionscare home admission from hospital is common and yet there are no established standards to support best practice. Decisions should involve the whole multidisciplinary team in partnership with patients and families. Documentation of assessment in the case notes is variable. We advocate the development of interdisciplinary standards to support the assessment of this vulnerable and complex group of patients.

Translational relevance:Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, with around 1.3 million cases diagnosed each year. Efforts to develop biomarkers of prognosis and response to chemotherapy in CRC have resulted in stratification systems based on components of the tumour microenvironment (TME), highlighting the importance of characterising both molecular and pathological features. The DNA Damage Immune Response (DDIR) transcriptional assay was developed as a predictive biomarker for identifying breast cancer (BC) patients that benefit from DNA-damaging chemotherapy, based on signalling associated with defective homologous recombination DNA repair. Here we show that the DDIR signature does not predict outcomes from oxaliplatin based chemotherapy for localised or metatastic CRC patients in clinical trials. We show that although this predictive assay identifies tumours enriched for defects in the DNA mismatch repair machinery, it primarily identifies immune-rich, albeit exhausted, CRC tumours with competent repair signalling that may respond to immune checkpoint blockade.