Variation in collagenase Clostridium histolyticum practice patterns: a Survey of ISSM Members.

Collagenase clostridium histolyticum (CCH, Xiaflex, Xiapex) is the only FDA-approved medication for treatment of Peyronie's disease. It is unclear how practitioners actually use CCH in their own practices. The objectives of the study were: (1) to identify variability in practice patterns for CCH among practitioners, (2) to assess adherence to the package insert instructions, and (3) to evaluate whether provider satisfaction was associated with adherence to instructions. A 30-question online survey was distributed to 1270 members of the International Society for Sexual Medicine (ISSM) from the EU, USA, Canada and Australia. Of the 30 questions, 10 survey questions had only one response consistent with the CCH package insert recommendations. An "adherence" score was calculated for each survey participant depending on how many of these questions were answered correctly. The average adherence scores of various groups were compared using a student's t-test. A chi-squared test was used to determine association between categorical variables. Of 202 total responses, 132 practitioners reported using CCH out of 1270 ISSM members from countries where CCH is available (10.4% response rate). Practitioners from outside the USA were more likely to be satisfied with CCH (p = 0.006), and more experienced users (>20 uses) were more likely to be satisfied than less experienced users (<10 uses) (p = 0.046). Satisfied users of CCH did not have significantly different adherence scores than non-satisfied users. Even though 67% of practitioners believed they followed the package insert guidelines, only 11% adhered to all the recommendations evaluated by the survey. Treatment adherence to package insert guidelines does not appear to be associated with provider satisfaction. We believe there is utility in seeing a snapshot of these practice patterns so practitioners may feel more comfortable adapting their own practice in light of newer data supporting alternative administration methods.

Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer.

We identified new gene fusions in patients with lung cancer harboring the kinase domain of the NTRK1 gene that encodes the high-affinity nerve growth factor receptor (TRKA protein). Both the MPRIP-NTRK1 and CD74-NTRK1 fusions lead to constitutive TRKA kinase activity and are oncogenic. Treatment of cells expressing NTRK1 fusions with inhibitors of TRKA kinase activity inhibited autophosphorylation of TRKA and cell growth. Tumor samples from 3 of 91 patients with lung cancer (3.3%) without known oncogenic alterations assayed by next-generation sequencing or fluorescence in situ hybridization demonstrated evidence of NTRK1 gene fusions.