Rationale: Fluorescence molecular endoscopy (FME) is an emerging technique that has the potential to improve the 22% colorectal polyp detection miss-rate. We determined the optimal dose-to-imaging interval and safety of FME using EMI-137, a c-Met targeted fluorescent peptide, in a population at high-risk for colorectal cancer. Methods: We performed in vivo FME and quantification of fluorescence by multi-diameter singlefiber reflectance, single-fiber fluorescence spectroscopy in 15 patients with a dysplastic colorectal adenoma. EMI-137 was intravenously administered (0.13mg/kg) at a one-, two-or three-hour dose-to-imaging interval (N=3 patients per cohort). Two cohorts were expanded to six patients based on target-to-background ratios (TBR). Fluorescence was correlated to histopathology and c-Met expression. EMI-137 binding specificity was assessed by fluorescence microscopy and in vitro experiments. Results: FME using EMI-137 appeared to be safe and well tolerated. All dose-to-imaging intervals showed significantly increased fluorescence in the colorectal lesions compared to surrounding tissue, with a TBR of 1.53, 1.66 and 1.74 respectively (mean intrinsic fluorescence (Qꞏ f a,x) = 0.035

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Dexamethasone has antitumor activity in metastatic castration resistant prostate cancer (mCRPC). We aimed to investigate intravenous liposome‐encapsulated dexamethasone disodium phosphate (liposomal dexamethasone) administration in mCRPC patients. In this exploratory first‐in‐man study, patients in part A received a starting dose of 10 mg followed by five doses of 20 mg liposomal dexamethasone at 2‐week intervals. Upon review of part A safety, patients in part B received 10 weekly doses of 18.5 mg. Primary outcomes were safety and pharmacokinetic profile, secondary outcome was antitumor efficacy. Nine mCRPC patients (5 part A, 4 part B) were enrolled. All patients experienced grade 1–2 toxicity, one (part B) patient experienced grade 3 toxicity (permanent bladder catheter‐related urosepsis). No infusion‐related adverse events occurred. One patient had upsloping glucose levels ≤9.1 mmol/L. Trough plasma concentrations of liposomal‐ and free dexamethasone were below the lower limit of quantification (LLOQ) in part A, and above LLOQ in three patients in part B ( t 1/2 ~50 h for liposomal dexamethasone), trough concentrations of liposomal‐ and free dexamethasone increased toward the end of the study. In seven of nine patients (78%) patients, stable disease was observed in bone and/or CT scans at follow‐up, and in one (part B) of these seven patients a >50% PSA biochemical response was observed. Bi‐ and once weekly administrations of IV liposomal dexamethasone were well‐tolerated. Weekly dosing enabled trough concentrations of liposomal‐ and free dexamethasone >LLOQ. The data presented support further clinical investigation in well‐powered studies. Clinical trial registration: ISRCTN 10011715.

Context Testicular germ cell tumour (TGCT) survivors are potentially at risk of developing osteoporosis, because of increased risk for disturbed bone remodelling associated with hypogonadism and anti‐cancer treatment. A number of studies show bone loss and increased fracture risk in TGCT survivors, but data are scarce. There are no clinical guidelines or recommendations issued to address skeletal health in this group of patients potentially at high risk for osteoporosis. Objective To conduct a systematic review of available literature addressing bone health in TGCT patients. Subgroup analysis was performed to identify risk factors for bone loss and increased fracture risk. Evidence Acquisition Relevant databases, including MEDLINE, Embase and the Cochrane Library, including all English written comparative studies addressing bone health in TGCT patients, were searched up to December 2021 and a narrative synthesis was undertaken. Risk of bias (RoB) was assessed using Cochrane ROBINS‐I tool. Evidence Synthesis Ten studies (eight cross‐sectional and two longitudinal), recruiting a total of 1997 unique TGCT patients, were identified and included in the analysis. Bone health was reported in various ways in different studies, and subgroups were defined heterogeneously, resulting in a widely varying prevalence of osteoporosis of up to 73.2% of patients. Six studies reported low BMD associated with higher luteinizing hormone levels and one study showed a correlation between follow up duration and bone loss. Conclusions TGCT survivors are at risk of developing osteoporosis and sustaining fragility fractures. Chemotherapy, pituitary‐gonadal axis dysfunction and ageing are key risk factors, although available data are scarce. With increasing survival of TGCT patients, a clear unmet need has been identified to systematically evaluate and monitor skeletal health in larger numbers of survivors in order to develop best clinical practice guidelines to manage the insidious but potentially preventable and treatable skeletal complications of TGCT.

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