Citations

Objectives: To validate a neck-shaft angle (NSA) correction formula using the known angle between the medullary nail and lag screw of an indwelling cephalomedullary nail (CMN). Methods: Pertrochanteric femur fractures were created in 7 synthetic femurs and reconstructed with a CMN. Anteroposterior x-rays were taken with the proximal femur in 0, 15, 30, and 45 degrees of internal/external rotation and 10 and 20 degrees of flexion with neutral rotation. The femoral NSA and the nail angle were measured on anteroposterior x-rays. The corrected NSA was obtained by multiplying the known nail angle by the quotient of the measured NSA over the measured nail angle. Results: With increasing degrees of internal or external rotation, the difference between the actual and the measured NSA increased. After correction using the known angle of the nail, the measured NSA was reduced to within 3 degrees of the actual NSA over all degrees of rotation. At neutral rotation, 15 degrees of external rotation, and 10 and 20 degrees of hip flexion, there was minimal difference between the actual NSA and the measured NSA, negating the effect of the correction formula. Conclusions: The measured NSA after CMN of intertrochanteric fractures is altered by hip rotation. This study validates the correction formula, which determines this difference by using the known angle between the lag screw and the nail.

BackgroundGradient nonlinearity (GNL) leads to biased apparent diffusion coefficients (ADCs) in diffusion‐weighted imaging. A gradient nonlinearity correction (GNLC) method has been developed for whole body systems, but is yet to be tested for the new compact 3T (C3T) scanner, which exhibits more complex GNL due to its asymmetrical design.PurposeTo assess the improvement of ADC quantification with GNLC for the C3T scanner.Study TypePhantom measurements and retrospective analysis of patient data.Phantom/SubjectsA diffusion quality control phantom with vials containing 0–30% polyvinylpyrrolidone in water was used. For in vivo data, 12 patient exams were analyzed (median age, 33).Field Strength/SequenceImaging was performed on the C3T and two commercial 3T scanners. A clinical DWI (repetition time [TR] = 10,000 msec, echo time [TE] = minimum, b = 1000 s/mm2) sequence was used for phantom imaging and 10 patient cases and a clinical DTI (TR = 6000–10,000 msec, TE = minimum, b = 1000 s/mm2) sequence was used for two patient cases.AssessmentThe 0% vial was measured along three orthogonal axes, and at two different temperatures. The ADC for each concentration was compared between the C3T and two whole‐body scanners. Cerebrospinal fluid and white matter ADCs were quantified for each patient and compared to values in literature.Statistical TestsPaired t‐test and two‐way analysis of variance (ANOVA).ResultsFor all PVP concentrations, the corrected ADC was within 2.5% of the reference ADC. On average, the ADC of cerebrospinal fluid and white matter post‐GNLC were within 1% and 6%, respectively, of values reported in the literature and were significantly different from the uncorrected data (P < 0.05).Data ConclusionThis study demonstrated that GNL effects were more severe for the C3T due to the asymmetric gradient design, but our implementation of a GNLC compensated for these effects, resulting in ADC values that are in good agreement with values from the literature.Level of Evidence: 4Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2018;48:1498–1507

TPS7577 Background: Nivolumab (nivo) is a PD-1 immune checkpoint inhibitor that augments T-cell activation and host anti-tumor responses. PD-1 blockade has shown promise in B- and T-cell non-Hodgkin lymphoma (NHL),1 but many patients (pts) with NHL do not respond or progress after response. Combination therapy using anti-tumor agents with complementary mechanisms of action and low immunosuppressive impact may result in more frequent and durable responses. Brentuximab vedotin (BV) is an anti-CD30 antibody–drug conjugate that induces cell cycle arrest and apoptosis, with activity in a range of NHL tumors.2,3 Tumor cells undergoing BV-induced apoptosis have shown subsequent immune-mediated anti-tumor cytotoxicity.4 Therefore, nivo and BV may synergize if combined for relapsed/refractory (RR) NHL. Methods: CheckMate 436 (NCT02581631) is a phase 1–2, open-label, international, single-arm study evaluating nivo + BV for CD30-expressing RR NHL (study start: Dec 2015) in pts with RR diffuse large B-cell lymphoma, peripheral T-cell lymphoma (excluding anaplastic large cell lymphoma), and cutaneous T-cell lymphoma (mycosis fungoides/Sézary syndrome); cohorts with primary mediastinal B-cell lymphoma (PMBL) and mediastinal gray zone lymphoma were made eligible in Sept 2016. Pts with PMBL must be aged ≥15 y (≥18 y for other histologies). All pts must have CD30-expressing disease, defined by CD30 on ≥1% of tumor cells or tumor-infiltrating lymphocytes by immunohistochemistry. In the phase 1 component, 6 pts will receive nivo and BV until disease progression or unacceptable toxicity. In the phase 2 component, ~130 more pts across the 5 histologies will be enrolled and treated at the recommended dose. Primary endpoints: safety, tolerability, and investigator-assessed objective response rate; secondary endpoints: duration of response and complete response (CR), CR rate, and progression-free and overall survival. Accrual is ongoing. References: 1. Lesokhin A et al. JCO 2016;34:2698–704 2. Jacobsen E et al. Blood 2015;125:1394–402 3. Horwitz S et al. Blood 2014;123:3095–100 4. Gardai S et al. Cancer Res 2015;75(15 Suppl):2469 [abstract]. Clinical trial information: NCT02581631.

e19525 Background: Rearrangements of the immunoglobulin heavy chain (IGH) on chromosome 14 are identified by FISH in about 15-20% of patients (pts) with newly diagnosed multiple myeloma (MM). Historically there is variation on the significance on prognosis of these rearrangements: typically, t(4;14), t(14;16) and t(14;20) have high risk (HR), and t(11;14) have standard risk (SR). A recent study (Kaufman et al, Leukemia. 2016 30:633-9) suggests that t(11;14) may confer a worse prognosis We report the prognostic significance of t(11;14) in a single-institution MM cohort. Methods: 87 pts with t(11;14) by CD 138 selected FISH at diagnosis were identified, pts without symptomatic MM were excluded. Cox regression was used for statistical analysis. Progression free survival (PFS), and overall survivals (OS) from diagnosis and post autologous stem cell transplant (ASCT) were analyzed by Kaplan-Meier. Results: Median age at diagnosis was 62 years, 45 pts (52%) were male, and 24 pts (27%) had ISS 3. All pts received either a proteasome inhibitor or an immunomodulatory agent, and 42 (48%) received triplet treatment as induction. Sixty-nine (79%) pts had ASCT, and overall response rate (ORR, partial response or better) post ASCT was 73%. For pts with HR FISH (defined as t(14;16), p53 del, 1q21 gain or 1p del) compared to SR FISH, the ORR post ASCT was 70% vs 77% (p = 0.67). OS from diagnosis was 93% at 3 years, 74% at 4 years and 51% at 5 years. Seven patients (8%) developed plasma cell leukemia, and there was no association between HR and SR FISH (p = 0.66). In multivariate analysis, ISS stage was an independent risk factor for mortality; pts with stage 3 had 7.3 times (CI: 1.16-36.4) and 5.7 times (CI: 1.63-20.0) the risk of mortality than pts with stage 1 and 2. Having an ASCT reduced mortality by 87% (CI: 0.04-0.41). Conclusions: Despite the use of novel therapies the OS at 5 years of our pts with MM was not significantly improved compared to SEER data from 1992-2013 (51% vs 48.5%). Pts with t(11;14) who had ASCT had increased survival compared to those who did not. Our results suggest that t(11;14) may confer a worse prognosis. Further prospective studies evaluating the risk of t(11;14) are warranted.

8044 Background: Racial disparities of FISH abnormalities in multiple myeloma (MM) have been well described in whites (W) but partially described in minorities (M) (Paulus et al, ASH 2016, 4432). We aimed to explore racial-based differences of FISH abnormalities using the largest cohort of m to date. Methods: CD-138 selected FISH was done on 799 consecutive patients (pts). Pts without symptomatic MM, and biopsy >6 months after diagnosis were excluded. The abnormalities evaluated included standard and intermediate risk: IGH rearrangements (IGH r), t(4;14), t(11;14), and high risk: t(14;20), t(14;16), del13q, del 17p, 1q21. Chi-square was used for statistical analysis. Due to smaller numbers, all m (Hispanic (H), Black (B), Asian (A) and Other (O)) were included into the same group for statistical analysis. Results: 482 pts were eligible, 343 (71%) were W, 52 (10%) H, 50 (10%) B, 19 (3%) A, and 18 (3%) O. Median age was 65 years, 54% were male, and 26% ISS stage 3. There were no were no statistically significant differences in FISH abnormalities between the m (Table1). Overall W had more abnormalities in IGH r, t(4;14), t(11;14), t(14:20), 1q21 gain compared to M. Most notably W had more IGH r (39% vs 28%; p=0.019) and t(11;14) (20% vs 12%; p=0.024). There were no statistically significant differences between W and m in the high risk FISH abnormalities. Conclusions: We had significant differences in FISH compared to M. W had more IGH r and t(11;14) than M, and there was no difference in high risk FISH abnormalities between W and M. This study confirms the biological racial disparities that exist in minorities with MM. Further studies with more inclusion of minorities are needed to elucidate these disparities and its effects on risk stratification and outcomes. [Table: see text]

5045 Background: Trophoblastic cell-surface antigen (Trop-2) is a transmembrane glycoprotein that is highly expressed in many solid tumors. Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate of an anti-Trop-2 humanized antibody with SN-38. Early clinical trials have shown high response rates in a broad range of diseases including triple negative breast and urothelial cancers. We evaluated Trop-2 expression in tumor biopsies and circulating tumor cells (CTCs) from men with mCRPC (metastatic castrate-resistant prostate cancer). Methods: Trop-2 expression was evaluated from mCRPC biopsies from patients (Pts) treated with abiraterone acetate (AA) on the PROMOTE clinical trial, CTCs from a separate cohort treated with either enzalutamide or AA. Trop-2 CTCs were compared with EpCAM captured CTCs using a microscale technology termed the VERSA (Vertical Exclusion-based Rare Sample Analysis) platform to compare protein and gene expression signatures of resistance to these agents. Results: RNA sequencing identified Trop-2 gene expression in > 70% of metastatic biopsies. The AR splice variant V7 was found in 48 biopsies that also expressed Trop-2. Trop-2 expression was not altered by treatment with AA at 12 weeks. The number of CTCs captured from 25 pts with Trop-2 or EpCAM were closely correlated (R2= 0.84). Gene expression analysis showed similar patterns of expression for the TROP-2 and EPCAM captured cells. AR splice variant expression (AR-V7, AR-V9) in Trop-2 and EpCAM CTCs was detected in 33% of patients. Expression of neuroendocrine markers was identified in 40% of Trop-2 CTCs. Conclusions: Trop-2 is frequently expressed in mCRPC and co-expressed in tumors that express AR splice variants. Trop-2 CTCs are detected in CRPC pts previously treated with AA or Enzalutamide that also express multiple AR splice variants and neuroendocrine markers. The results support Trop-2 expression as predictive biomarker of sensitivity to targeted therapies tumors resistant to AA or Enzalutamide. Men with mCRPC are being enrolled on a Phase I trial with IMMU-132, and multi-site Phase II clinical trial in men who have progressed on AA or Enzalutamide is being finalized.