IMPORTANCE Gut dysbiosis impairs response to immune checkpoint inhibitors (ICIs) and can be caused by broad-spectrum antibiotic (ATB) therapy. OBJECTIVE To evaluate whether there is an association between ATB therapy administered concurrently (cATB) or prior (pATB) to ICI therapy and overall survival (OS) and treatment response to ICI therapy in patients with cancer treated with ICIs in routine clinical practice. DESIGN, SETTING, AND PARTICIPANTS This prospective, multicenter, cohort study conducted at 2 tertiary academic referral centers recruited 196 patients with cancer who received ICI therapy between January 1, 2015, and April 1, 2018, in routine clinical practice rather than clinical trials.MAIN OUTCOMES AND MEASURES Overall survival calculated from the time of ICI therapy commencement and radiologic response to ICI treatment defined using the Response Evaluation Criteria in Solid Tumors (version 1.1), with disease refractory to ICI therapy defined as progressive disease 6 to 8 weeks after the first ICI dose without evidence of pseudoprogression. RESULTS Among 196 patients (137 men and 59 women; median [range] age, 68 [27-93] years) with non-small cell lung cancer (n = 119), melanoma (n = 38), and other tumor types (n = 39), pATB therapy (HR, 7.4; 95% CI, 4.3-12.8; P < .001), but not cATB therapy (HR, 0.9; 95% CI, 0.5-1.4; P = .76), was associated with worse OS (2 vs 26 months for pATB therapy vs no pATB therapy, respectively) (hazard ratio [HR], 7.4; 95% CI, 4.2-12.9) and a higher likelihood of primary disease refractory to ICI therapy (21 of 26 [81%] vs 66 of 151 [44%], P < .001). Overall survival in patients with non-small cell lung cancer (2.5 vs 26 months, P < .001), melanoma (3.9 vs 14 months, P < .001), and other tumor types (1.1 vs 11, P < .001) was consistently worse in those who received pATBs vs those who did not. Multivariate analyses confirmed that pATB therapy (HR, 3.4; 95% CI, 1.9-6.1; P < .001) and response to ICI therapy (HR, 8.2; 95% CI, 4.0-16.9; P < .001) were associated with OS independent of tumor site, disease burden, and performance status.CONCLUSIONS AND RELEVANCE Despite being limited by sample size, geographic origin, and the lack of correlative analyses on patients' gut microbiota, this study suggests that pATB therapy but not cATB therapy is associated with a worse treatment response and OS in unselected patients treated with ICIs in routine clinical practice. Mechanistic studies are urgently required to investigate ATB-mediated alterations of gut microbiota as a determinant of poorer outcome following ICI treatment.

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Testicular cancer is a rare tumour with the potential for cure at diagnosis. It is important, however, to identify those patients with metastases at presentation so as to ensure that the optimum treatment strategy is employed. Many criteria have been used to try to place patients into high- or low-risk groups, with variable success. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has the potential to identify active disease and thereby influence further management. Here we report on a retrospective study of the use of FDG-PET in the detection of metastatic testicular carcinoma at diagnosis. Thirty-one patients [13 with seminoma and 18 with non-seminomatous germ cell tumours (13 teratomas, 5 mixed)] were staged by FDG-PET scanning. The imaging was performed using a Siemens ECAT 951 scanner. All results were assessed on the basis of histology or clinical follow-up. FDG-PET scan identified metastatic disease in ten and was negative in 16; there were no false-positives and five false-negatives. There were six patients in whom FDG-PET was negative and computed tomography was regarded as suspicious but follow-up was inconclusive. The positive predictive value was 100%. The negative predictive value was 76% or 91%, depending on whether the aforementioned six cases were regarded as true-negatives or false-negatives. It may be concluded that FDG-PET is capable of detecting metastatic disease at diagnosis that is not identified by other imaging techniques. These preliminary results are sufficient to suggest that a large prospective study should be performed to evaluate the role of FDG-PET in primary staging of disease.

147 Background: Antibiotic therapy (ATB) may impair efficacy of immune checkpoint inhibitors (ICPI) through modulation of gut microbiota. Evidence is however limited to trial participants with non-small cell (NSCLC) and renal cell carcinoma (RCC). In this multi-centre study, we validated the impact of ATB in patients (pts) treated with ICPI in routine practice, irrespective of tumour site. Methods: We analysed a prospective dataset of pts treated with ICPI in 2 centres. We documented timing and duration of ATB administered within 1 month prior to ICPI treatment (pATB) or concurrently (cATB) until ICPI cessation. We evaluated response and overall survival (OS) across ATB+/-. Results: We enrolled 196 pts with NSCLC (n=119), Melanoma (n=38) and other histotypes (n=39). Most pts were male (n=137, 70%) with performance status 0-1 (n=159, 84%) and a median number of 2 metastatic sites (range 0-7). Pts received mostly anti-PD-1/PD-L1 ICPI (n=189, 96%) as first-line metastatic therapy (n=120, 62%). Twenty-nine patients (15%) received pATB with penicillins (n=22, 75%) for ≤7 days (n=26, 89%). Sixty-eight pts (35%) received penicillin-based (n=49, 72%) cATB for ≤7 days (n=39, 88%). Respiratory infections were the commonest indication for both pATB (n=16, 55%) and cATB (n=38, 85%). pATB (p<0.001) but not cATB (p=0.76) was associated with worse OS (26 vs. 2 months, Hazard Ratio 7.4, 95% CI 4.2-12.9) and increased likelihood of primary refractoriness to ICPI (44% vs 81%, p<0.001). pATB consistently worsened OS in NSCLC (26 vs. 2.5 months, p<0.001), melanoma (14 vs 3.9 months, p<0.001) and other tumours (11 vs 1.1 months, p<0.001). In multi-variable analyses pATB (p<0.001, HR 3.4, 95% CI 1.9-6.1) and response to ICPI (p<0.001, HR 8.2, 95% CI 4.0-16.9) predicted for OS independent of histotype, tumour burden, PS. Conclusions: This study suggests pATB to exert an independent detrimental effect on response and survival in unselected pts treated with ICPI in routine clinical practice. Mechanistic studies are urgently required to investigate ATB-mediated alterations of gut microbiota as a determinant of poorer outcome following ICPI treatment.

Patients with hypertensive emergencies, malignant hypertension and acute severe hypertension are managed heterogeneously in clinical practice. Initiating anti-hypertensive therapy and setting BP goal in acute settings requires important considerations which differ slightly across various diagnoses and clinical contexts. This position paper by British and Irish Hypertension Society, aims to provide clinicians a framework for diagnosing, evaluating, and managing patients with hypertensive crisis, based on the critical appraisal of available evidence and expert opinion.