Induction therapy with ipilimumab and nivolumab followed by consolidative chemoradiation as organ-sparing treatment in urothelial bladder cancer: study protocol of the INDIBLADE trial.

Introduction: Studies that assessed the efficacy of pre-operative immune checkpoint blockade (ICB) in locally advanced urothelial cancer of the bladder showed encouraging pathological complete response rates, suggesting that a bladder-sparing approach may be a viable option in a subset of patients. Chemoradiation is an alternative for radical cystectomy with similar oncological outcomes, but is still mainly used in selected patients with organ-confined tumors or patients ineligible to undergo radical cystectomy. We propose to sequentially administer ICB and chemoradiation to patients with (locally advanced) muscle-invasive bladder cancer. Methods: The INDIBLADE trial is an investigator-initiated, single-arm, multicenter phase 2 trial. Fifty patients with cT2-4aN0-2M0 urothelial bladder cancer will be treated with ipilimumab 3 mg/kg on day 1, ipilimumab 3 mg/kg plus nivolumab 1 mg/kg on day 22, and nivolumab 3 mg/kg on day 43 followed by chemoradiation. The primary endpoint is the bladder-intact event-free survival (BI-EFS). Events include: local or distant recurrence, salvage cystectomy, death and switch to platinum-based chemotherapy. We will also evaluate the potential of multiparametric magnetic resonance imaging of the bladder to identify non-responders, and we will assess the clearance of circulating tumor DNA as a biomarker for ICB treatment response. Discussion: This is the first trial in which the efficacy of induction combination ICB followed by chemoradiation is being evaluated to provide bladder-preservation in patients with (locally advanced) urothelial bladder cancer. Clinical Trial Registration: The INDIBLADE trial was registered on clinicaltrials.gov on January 21, 2022 (NCT05200988).

Outcome of penetrating chest injuries in an urban level I trauma center in the Netherlands.

INTRODUCTION: Most patients with penetrating chest injuries benefit from early treatment with chest tube drainage or surgery. Although penetrating chest injury is not uncommon, few descriptive studies are published, especially in Europe. The aim of this study was to review our experience and further improve our management of penetrating chest injuries in a level I trauma center in the Netherlands. METHODS: All patients with penetrating chest injury between August 2004 and December 2012 were included. Demographics, mechanism of injury, physiological parameters, Injury Severity Scores (ISS), surgical and non-surgical treatment, length of intensive care unit (ICU) stay, length of hospital stay (LOS), complications and rate of mortality were collected. RESULTS: A total of 159 patients were analyzed. Patients included 116 (73 %) stab wounds and 34 (21 %) gunshot wounds. In 27 patients (17 %), cardiac injury was seen. The mean ISS was 12. Almost half of all patients (49 %) were treated with only chest tube drainage. Alternatively, surgical treatment was performed in 24 % of all cases. Anterolateral incision was most frequently used to gain access to the thoracic cavity. The mean LOS was 9 days. Among all patients, 17 % were admitted to the ICU with a mean stay of 3 days. In 18 (11 %) patients, one or more complications occurred. The 30-day mortality was 7.5 %. CONCLUSION: Patients presenting with penetrating chest injury are not uncommon in the Netherlands and can mostly be treated conservatively. In one-fourth of the patients, surgical treatment is performed. A structural and vigorous approach is needed for good clinical outcome.