Citations

TPS532 Background: Recent studies have shown that FGFR2 fusions may represent recurrent (prevalence ~10-15% in larger cohorts) driver events amenable to therapeutic targeting in patients with advanced, intrahepatic cholangiocarcinoma. Methods: This single arm pilot study (NCT02265341) is being conducted at 3 centers (Mayo Clinic Arizona, Mayo Clinic Florida and Mayo Clinic Rochester; enrollment initiated December 2014). Next-generation sequencing based assays and a FISH-break apart assay are used to identify tumors with FGFR2 fusions. Patients must additionally have histologically/cytologically confirmed cholangiocarcinoma, ECOG performance score 0-2, measurable disease, preserved hematologic/renal and hepatic function and absence of cardiac events/stroke in the preceding 6 months. Ponatinib is administered at 45 mg once daily. Patients will be treated until disease progression, intolerable toxicity or patient decision to not pursue further therapy. The primary objective of the study is to estimate the clinical benefit rate (defined as composite of partial response rate, complete response rate and stable disease rate ≥ 4 months; as defined by RECIST criteria v1.1). Secondary endpoints include estimation of progression-free survival, overall survival, CA19-9 response rate (defined as > 50% reduction from baseline) and evaluation of the overall adverse event profile of ponatinib in this patient population. Translational objectives include serial circulating DNA (ct-DNA) monitoring, target knockdown assessments in tumor tissue (p-FGFR2, p-FRS2, p-Akt and p-ERK) and evaluation of mechanisms of resistance through comparison of baseline and progression biopsy samples using multi-platform sequencing (exome, RNA-Seq and methyl-Seq). Additionally, quality of life assessments will be evaluated using EORTC-QLQ-C30 and BIL21 tools. A total of 30 patients will be enrolled into the study (12 of 30 patients have been enrolled). The trial is designed using an underlying assumption of clinical benefit rate (CBR) of 5% with significance level of 0.15 and 80% power to detect a 20% CBR. Clinical trial information: NCT02265341.

Background: Appropriate patient selection is critical when hip arthroscopy is considered in the setting of borderline dysplasia (BD). It is presumable that excessive femoral anteversion (EFA) and BD may contraindicate arthroscopy. Hypothesis: Patients with combined EFA and BD (EFABD) demonstrate significantly inferior short-term outcomes after arthroscopic labral preservation and capsular closure when compared with a similar control group with normal lateral coverage and femoral anteversion. Study Design: Cohort study; Level of evidence, 3. Methods: Data were prospectively collected and retrospectively reviewed on patients undergoing hip arthroscopy between April 2010 and November 2014. The EFABD group’s inclusion criteria were BD (lateral center-edge angle, 18°-25°), labral tear, capsular closure, and femoral version ≥20°, as well as preoperative modified Harris Hip Score, Nonarthritic Hip Score, Hip Outcome Score–Sports Specific Subscale, and visual analog scale. Exclusion criteria were workers’ compensation, preoperative Tönnis grade >1, microfracture, abductor pathology, or previous ipsilateral hip surgery or conditions. Patients in the EFABD group were matched 1:2 to a similar control group with normal coverage and femoral anteversion by age at surgery ± 6 years, sex, body mass index ± 5, acetabular Outerbridge grade (0, 1 vs 2, 3, 4), and iliopsoas fractional lengthening. Results: Sixteen EFABD cases were eligible for inclusion, and 100% follow-up was obtained at ≥2 years postoperatively. Twelve EFABD cases were matched to 24 control cases. Mean femoral version was 22.4° in the EFABD group and 10.2° in the control group ( P = .01). Mean lateral center-edge angle was 22.1° in the EFABD group and 31.5° in the control group ( P < .0001). Acetabuloplasty was performed significantly more frequently in the control group ( P = .0006). No other significant differences were found regarding demographics, findings, procedures, or preoperative scores. At latest follow-up, the EFABD group demonstrated significantly lower mean modified Harris Hip Score (76.1 vs 85.9; P = .005), Nonarthritic Hip Score (74.8 vs 88.5; P < .0001), Hip Outcome Score–Sports Specific Subscale (58.3 vs 78.4; P = .02), and patient satisfaction (7.1 vs 8.3; P = .005). There were 4 secondary surgical procedures (33.3%) in the EFABD group and 1 (4.2%) in the control group ( P = .03). One patient in each group required arthroplasty. Conclusion: Patients treated with arthroscopic labral preservation and capsular closure in the setting of EFABD demonstrated significant improvements from presurgery to latest follow-up. However, their results are significantly inferior when compared with a matched-controlled group. Consideration of periacetabular osteotomy or femoral osteotomy may be warranted in the setting of EFABD to achieve optimal benefit.