The Christie Research Publications Repository: Recent submissions
Now showing items 21-40 of 15356
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Evaluating debio 1347 in patients with <i>FGFR</i> fusion-positive advanced solid tumors from the FUZE multicenter, open-label, phase II basket trialPurpose: This multicenter phase II basket trial investigated the efficacy, safety, and pharmacokinetics of Debio 1347, an investigational, oral, highly selective, ATP-competitive, small molecule inhibitor of FGFR1-3, in patients with solid tumors harboring a functional FGFR1-3 fusion. Patients and Methods: Eligible adults had a previously treated locally advanced (unresectable) or metastatic biliary tract (cohort 1), urothelial (cohort 2), or another histologic cancer type (cohort 3). Debio 1347 was administered at 80 mg once daily, continuously, in 28-day cycles. The primary endpoint was the objective response rate. Secondary endpoints included duration of response, progression-free survival, overall survival, pharmacokinetics, and incidence of adverse events. Results: Between March 22, 2019, and January 8, 2020, 63 patients were enrolled and treated, 30 in cohort 1, 4 in cohort 2, and 29 in cohort 3. An unplanned preliminary statistical review showed that the efficacy of Debio 1347 was lower than predicted, and the trial was terminated. In total, 3 of 58 evaluable patients had partial responses, representing an objective response rate of 5%, with a further 26 (45%) having stable disease (>= 6 weeks duration). Grade >= 3 treatment-related adverse events occurred in 22 (35%) of 63 patients, with the most common being hyperphosphatemia (13%) and stomatitis (5%). Two patients (3%) discontinued treatment due to adverse events. Conclusions: Debio 1347 had manageable toxicity; however, the efficacy in patients with tumors harboring FGFR fusions did not support further clinical evaluation in this setting. Our transcriptomic-based analysis characterized in detail the incidence and nature of FGFR fusions across solid tumors.
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Gynecologic pathology journal club: a 2-year, worldwide virtual learning experience with a focus on mentorship and inclusionJournal clubs (JCs) are a common format used in teaching institutions to promote trainee engagement and develop skills in seeking out evidence-based medicine and critically evaluating literature. Digital technology has made JC accessible to worldwide audiences, which allows for increased inclusion of globally diverse presenters and attendees. Herein we describe the experience of the first 2 years of a virtual gynecologic pathology JC designed with the goal of providing mentorship and increasing inclusivity. JC began in a virtual format in April 2020 in response to the need for remote learning during the coronavirus disease 2019 pandemic. Each JC had 1 moderator, lasted 1 hour, featured up to 3 trainees/early-career pathologists, and covered articles on gynecologic surgical pathology/cytopathology. Trainees were recruited through direct contact with moderators and advertising through social media (eg, Twitter). A template was used for all presentations, and before presenting, live practice sessions were conducted with the moderator providing constructive feedback and evaluations were provided to presenters and attendees for feedback. Recordings of the meetings were made publicly available after the event through YouTube, a society website, and emails to registrants. Fifty-nine presenters participated, covering 71 articles. Most were trainees (53/59; 89%) from North America (33/59; 56%), with additional presenters from Asia (14/59; 24%), Australia/Oceania (5/59; 8%), Africa (4/59; 7%), and Europe (3/59; 5%). An average of 20 hours were spent per month by moderators on the selection of papers, meeting preparation, and provision of mentorship/feedback. Live events had a total of 827 attendees, and 16,138 interactions with the recordings were noted. Among those who self-identified on provided surveys, the attendees were most commonly from Europe (107/290; 37%) and were overwhelmingly practicing pathologists (275/341; 81%). The experience, including mentorship, format, and content, was positively reviewed by attendees and presenters. Virtual JC is an inclusive educational opportunity to engage trainees and early-career pathologists from around the world. The format allowed for the JC to be widely viewed by attendees from multiple countries, most being practicing pathologists. Based on feedback received, virtual JC appears to expand the medical knowledge of the attendees and empower presenters to develop their expertise and communication skills.
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Pilot study of lung cancer screening for survivors of hodgkin lymphomaHodgkin lymphoma (HL) treatment increases the risk of lung cancer. Most HL survivors are not eligible for lung cancer screening (LCS) programs developed for the general population, and the utility of these programs has not been tested HL survivors. We ran a LCS pilot in HL survivors to describe screening uptake, participant characteristics, impact of a decision aid and screen findings. HL survivors treated >= 5 years ago with mustine/procarbazine and/or thoracic radiation, were identified from a follow-up database and invited to participate. Participants underwent a low-dose computed tomography (LDCT) reported using protocols validated for the general population. Two hundred and eighteen individuals were invited, 123 were eligible, 102 were screened (58% response rate): 58% female, median age 52 years, median 22 years since treatment; 91.4% were deemed to have made an informed decision; participation was not influenced by age, sex, years since treatment or deprivation. Only three of 35 ever-smokers met criteria for LCS through the program aimed at the general population. Baseline LDCT results were: 90 (88.2%) negative, ten (9.8%) indeterminate, two (2.0%) positive. Two 3-month surveillance scans were positive. Of four positive scans, two patients were diagnosed with small-cell lung cancer; one underwent curative surgery. Coronary artery calcification was detected in 36.3%, and clinically significant incidental findings in 2.9%. LDCT protocols validated in ever-smokers can detect asymptomatic early-stage lung cancers in HL survivors. This finding, together with screening uptake and low false positive rates, supports further research to implement LCS for survivors .