Citations

8055 Background: mTOR inhibition with intravenous temsirolimus (Wyeth Pharmaceuticals) has been associated with responses in mantle cell lymphoma (J Clin Oncol 23;5347, 2005) as well as other lymphomas (Blood 108 (11) 2483; 2006). This phase II study tested the oral mTOR inhibitor everolimus (RAD001, Novartis Pharmaceuticals) in three simultaneous two-stage phase II lymphoma studies - aggressive (group 1), indolent (group 2), or uncommon (group 3). The goals were to learn the toxicity profile and to assess the anti-tumor response. Planned interim analysis for groups 1 and 3 have been completed and are the subject of this report. Methods: Patients (pts) received 10 mg PO daily for each 28 day cycle (up to 12) and restaged after 2, 6, and 12 cycles. The primary endpoint is the confirmed response rate, including CR, CRu or PR. 12 pts were enrolled in stage 1 of each study. At least 1 success in 12 is required to proceed to stage 2, to a total of 37 pts. Overall, the treatment will be considered promising if 4 or more successes are observed in all 37 pts in each group. Results: The median age of the 12 pts in group 1 was 68.5 yrs (range: 53–80), with a median of 3 (range, 1–15) prior therapies. Four pts had a prior stem cell transplant (SCT). Pts completed a median of 7 (range, 1–12) cycles of therapy. 6 confirmed responses have been achieved (1 CR, 5 PR), meeting the overall criteria for promising results in this study. Common grade 3 adverse events (AEs) include thrombocytopenia (3 pts) and anemia (2 pts). For group 3, the median age was 49 yrs (range, 27–78), with a median of 7 (range, 1–13) prior therapies and 6 pts had a prior SCT. Pts have completed a median of 6.5 cycles (range, 1–11). 5 confirmed responses have been achieved (5 PR), meeting the criteria for this regimen to be considered promising. Of these 5 patients, 3 had HD, 1 T-cell NHL, and 1 had macroglobulinemia. Common grade 3 AEs include anemia (3 pts) and thrombocytopenia (2 pts). No grade 4 AEs were reported. Conclusions: Oral everolimus has activity in a spectrum of lymphomas with acceptable toxicity. The responses observed in both group 1 and group 3 met the criteria to continue accrual. These results provide the rationale for additional studies with this novel class of agents and to integrate mTOR inhibitors into salvage treatment regimens. No significant financial relationships to disclose.

OBJECTIVE This study’s purpose was to improve understanding of the forces driving the complex mechanical interaction between embolic material and current stroke thrombectomy devices by analyzing the histological composition and strength of emboli retrieved from patients and by evaluating the mechanical forces necessary for retrieval of such emboli in a middle cerebral artery (MCA) bifurcation model. METHODS Embolus analogs (EAs) were generated and embolized under physiological pressure and flow conditions in a glass tube model of the MCA. The forces involved in EA removal using conventional endovascular techniques were described, analyzed, and categorized. Then, 16 embolic specimens were retrieved from 11 stroke patients with large-vessel occlusions, and the tensile strength and response to stress were measured with a quasi-static uniaxial tensile test using a custom-made platform. Embolus compositions were analyzed and quantified by histology. RESULTS Uniaxial tension on the EAs led to deformation, elongation, thinning, fracture, and embolization. Uniaxial tensile testing of patients’ emboli revealed similar soft-material behavior, including elongation under tension and differential fracture patterns. At the final fracture of the embolus (or dissociation), the amount of elongation, quantified as strain, ranged from 1.05 to 4.89 (2.41 ± 1.04 [mean ± SD]) and the embolus-generated force, quantified as stress, ranged from 63 to 2396 kPa (569 ± 695 kPa). The ultimate tensile strain of the emboli increased with a higher platelet percentage, and the ultimate tensile stress increased with a higher fibrin percentage and decreased with a higher red blood cell percentage. CONCLUSIONS Current thrombectomy devices remove emboli mostly by applying linear tensile forces, under which emboli elongate until dissociation. Embolus resistance to dissociation is determined by embolus strength, which significantly correlates with composition and varies within and among patients and within the same thrombus. The dynamic intravascular weakening of emboli during removal may lead to iatrogenic embolization.

PAX1deficiency causes a syndromic form of SCID by altering differentiation of thymic epithelial cells and other pharyngeal pouch tissues.

Background: Lateral epicondylitis, or tennis elbow, is a painful degenerative disorder that commonly occurs in adults between 40 and 60 years of age. Normal saline (NS) injections have been used as placebo through a large number of randomized controlled trials (RCTs) focused on the treatment of lateral epicondylitis. Purpose: This meta-analysis of RCTs aimed to assess the therapeutic effect of NS injections on lateral epicondylitis symptoms and compare results with established minimal clinically important difference criteria. Study Design: Systematic review and meta-analysis. Methods: MEDLINE, Embase, Web of Science, and Scopus databases were searched for clinical trials reporting pain and joint function with the visual analog scale, Patient-Rated Tennis Elbow Evaluation, and Disabilities of the Arm, Shoulder and Hand in patients with lateral epicondylitis. The meta-analysis was conducted with a random effects model and generic inverse variance method. Heterogeneity was tested with the I 2 statistic index. Results: A total of 15 RCTs included in this meta-analysis revealed a significant improvement in pain (mean difference, 3.61 cm [95% CI, 2.29-4.92 cm]; P < .00001; I 2 = 88%; visual analog scale) and function (mean difference, 25.65 [95% CI, 13.30-37.99]; P < .0001; I 2 = 82%; Patient-Rated Tennis Elbow Evaluation / Disabilities of the Arm, Shoulder and Hand) after NS injection (≥6 months). Conclusion: NS injections yielded a statistically significant and clinically meaningful improvement in pain and functional outcomes in patients with lateral epicondylitis. New research should focus on better methods to diminish the potential confounders that could lead to this effect because NS injections could mask the real effect of an active therapeutic intervention in RCT. Registration: CRD42019127547 (PROSPERO).

OBJECTIVEThe level of radiation awareness by surgeons and residents in spinal surgery does not match the ubiquity of fluoroscopy in operating rooms in the United States. The present method of monitoring radiation exposure may contribute to the current deficiency in radiation awareness. Current dosimeters involve a considerable lag from the time that the surgical team is exposed to radiation to the time that they are provided with that exposure data. The objective of the current study was to assess the feasibility of monitoring radiation exposure in operating room personnel during lateral transpsoas lumbar interbody fusion (LLIF) and minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) procedures by using a wearable personal device with real-time feedback.METHODSOperating room staff participating in minimally invasive surgical procedures under a single surgeon during a 6-month period were prospectively enrolled in this study. All radiation dose exposures were recorded for each member of the surgical team (surgeon, assistant surgeon, scrub nurse, and circulating nurse) using a personal dosimeter (DoseAware). Radiation doses were recorded in microsieverts (μSv). Comparisons between groups were made using ANOVA with the Tukey post hoc test and Student t-test.RESULTSThirty-nine patients underwent interbody fusions: 25 underwent LLIF procedures (14 LLIF alone, 11 LLIF with percutaneous screw placement [PSP]) and 14 underwent MI-TLIF. For each operative scenario per spinal level, the surgeon experienced significantly higher (p < 0.035) average radiation exposure (LLIF: 167.9 μSv, LLIF+PSP: 424.2 μSv, MI-TLIF: 397.9 μSv) than other members of the team, followed by the assistant surgeon (LLIF: 149.7 μSv, LLIF+PSP: 242.3 μSv, MI-TLIF: 274.9 μSv). The scrub nurse (LLIF: 15.4 μSv, LLIF+PSP: 125.7 μSv, MI-TLIF: 183.0 μSv) and circulating nurse (LLIF: 1.2 μSv, LLIF+PSP: 9.2 μSv, MI-TLIF: 102.3 μSv) experienced significantly lower exposures. Radiation exposure was not correlated with the patient’s body mass index (p ≥ 0.233); however, it was positively correlated with increasing patient age (p ≤ 0.004).CONCLUSIONSReal-time monitoring of radiation exposure is currently feasible and shortens the time between exposure and the availability of information regarding that exposure. A shortened feedback loop that offers more reliable and immediate data would conceivably raise the level of concern for radiation exposure in spinal surgeries and could alter patterns of behavior, leading to decreased exposures. Further studies are ongoing to determine the effect of real-time dosimetry in spinal surgery.

Juvenile-onset systemic lupus erythematosus (JSLE) presents with an aggressive course and high morbidity associated with disease and treatment. JSLE patients have a poorer health-related quality of life (HRQoL) when compared with age-matched patients with other rheumatologic disorders. We aim to summarize the impact of current pharmacological therapies on the HRQoL of JSLE patients. Search strategies were developed across seven databases. Randomized clinical trials (RCTs) and cohort studies comparing interventions to standard therapy, placebo or pre-post cohort comparisons for more than 4 weeks were included. The outcome included self-reported scales compared at baseline and a therapeutic time point. Risk of bias was evaluated by using the Cochrane risk of bias tool and the Newcastle–Ottawa quality assessment scale. A total of 2812 articles were narrowed down to 309 for full-text screening. Four RCTs and one prospective cohort study, with a total of 634 JSLE patients, met the inclusion criteria. Four of the studies had a controlled intervention plus standard therapy compared with standard therapy alone or placebo. Multiple indices were used to evaluate HRQoL. These included the Pediatric Quality of Life Inventory, Childhood Health Assessment Questionnaire, Simple Measure of Impact of Lupus Erythematosus in Youngsters tool, Kids Fatigue Severity Scale and Child Depression Inventory. A single study reported a significant improvement while remaining studies reported no difference or failed to report the statistical analysis. Although HRQoL is significantly impaired in JSLE, evidence regarding its improvement is limited due to the small number of eligible studies, heterogeneity in scales, and HRQoL domains. A universal HRQoL questionnaire for JSLE needs to be established and used in both the research and clinical setting. All studies should adhere to reporting guidelines.

TPS592 Background: For advanced CCA, standard of care 1L systemic treatment is GEM + CIS. Genetic alterations in intrahepatic CCA provide potential therapeutic targets. Fibroblast growth factor receptor (FGFR) 2 gene rearrangements driving CCA tumorigenesis were identified almost exclusively in intrahepatic CCA patients (pts) (incidence, 10–16%). In phase 2, PEM (INCB054828), a selective, potent, oral FGFR1–3 inhibitor elicited an objective response rate (ORR) of 35.5% and median progression-free survival (PFS) of 6.9 months (mo) in previously treated, locally advanced or metastatic CCA with FGFR2 rearrangements (NCT02924376). FIGHT-302, a randomized, open-label, phase 3 study will evaluate efficacy and safety of 1L PEM vs GEM + CIS in unresectable/metastatic CCA with FGFR2 fusions or rearrangements (NCT03656536). Methods: Eligible pts are adults with confirmed unresectable/metastatic CCA; no prior systemic therapy for advanced disease < 6 mo before enrollment; radiographically measurable/evaluable disease (per RECIST v1.1); ECOG PS ≤1; documented FGFR2 fusions or rearrangements. Exclusions include clinically significant corneal or retinal disorder; history of calcium and phosphate homeostasis disorder or systemic mineral imbalance with ectopic soft tissue calcification; untreated CNS metastases or history of uncontrolled seizures. Pts will be randomized (1:1; stratified by region and tumor burden) to PEM 13.5 mg QD on a 21-day (d) cycle or GEM (1000 mg/m2) + CIS (25 mg/m2) on D1 and D8 of 21-d cycles (max 8). Crossover to PEM allowed after confirmed progression. PEM titration to 18 mg from cycle 2 allowed for pts without hyperphosphatemia (serum phosphate > 5.5 mg/dL) and Grade ≥2 treatment-related adverse events during cycle 1. Hyperphosphatemia will be managed with diet modifications, phosphate binders, diuretics, or dose adjustments. Treatment will continue until progression or unacceptable toxicity. Primary endpoint is PFS (by independent review). Secondary endpoints are ORR, overall survival, duration of response, disease control rate, safety, and quality of life. Four pts (target N = 432) are enrolled as of Sep 25, 2019. Clinical trial information: NCT03656536.

Abstract Background : Sex is recognized as a significant determinant of outcome among glioblastoma patients, but the relative prognostic importance of glioblastoma features has not been thoroughly explored for sex differences. Methods : Combining multi-modal MR images, biomathematical models, and patient clinical information, this investigation assesses which pretreatment variables have a sex-specific impact on the survival of glioblastoma patients (299 males and 195 females). Results : Among males, tumor (T1Gd) radius was a predictor of overall survival (HR=1.027, p=0.044). Among females, higher tumor cell net invasion rate was a significant detriment to overall survival (HR=1.011, p<0.001). Female extreme survivors had significantly smaller tumors (T1Gd) (p=0.010 t-test), but tumor size was not correlated with female overall survival (p=0.955 CPH). Both male and female extreme survivors had significantly lower tumor cell net proliferation rates than other patients (M p=0.004, F p=0.001, t-test). Conclusion : Despite similar distributions of the MR imaging parameters between males and females, there was a sex-specific difference in how these parameters related to outcomes.

Background While the review of radiotherapy treatment plans and charts by a medical physicist is a key component of safe, high‐quality care, very few specific recommendations currently exist for this task. Aims The goal of TG‐275 is to provide practical, evidence‐based recommendations on physics plan and chart review for radiation therapy. While this report is aimed mainly at medical physicists, others may benefit including dosimetrists, radiation therapists, physicians and other professionals interested in quality management. Methods The scope of the report includes photon/electron external beam radiotherapy (EBRT), proton radiotherapy, as well as high‐dose rate (HDR) brachytherapy for gynecological applications (currently the highest volume brachytherapy service in most practices). The following review time points are considered: initial review prior to treatment, weekly review, and end‐of‐treatment review. The Task Group takes a risk‐informed approach to developing recommendations. A failure mode and effects analysis was performed to determine the highest‐risk aspects of each process. In the case of photon/electron EBRT, a survey of all American Association of Physicists in Medicine (AAPM) members was also conducted to determine current practices. A draft of this report was provided to the full AAPM membership for comment through a 3‐week open‐comment period, and the report was revised in response to these comments. Results The highest‐risk failure modes included 112 failure modes in photon/electron EBRT initial review, 55 in weekly and end‐of‐treatment review, 24 for initial review specific to proton therapy, and 48 in HDR brachytherapy. A 103‐question survey on current practices was released to all AAPM members who self‐reported as working in the radiation oncology field. The response rate was 33%. The survey data and risk data were used to inform recommendations. Discussion Tables of recommended checks are presented and recommendations for best practice are discussed. Suggestions to software vendors are also provided. Conclusions TG‐275 provides specific recommendations for physics plan and chart review which should enhance the safety and quality of care for patients receiving radiation treatments.

Abstract Funding Acknowledgements None Background/Purpose: Anemia is a common condition in patients with cardiovascular disease. The effect of anemia in exercise stress testing has not been evaluated in a large cohort of patients. Methods We performed a retrospective review of patients undergoing exercise stress echocardiography over a 10 year period who had blood hemoglobin assessed within 48 hours of stress testing. World Health Organization cutoffs were used in defining the degree of anemia. The effect of anemia on exercise capacity and stress testing safety outcomes was assessed. Results In 15,652 patients, 90.3% were non-anemic, 7.6% mildly anemic, 2.1% moderately anemic, and 0.1% severely anemic. The incidence of serious supraventricular or ventricular arrhythmias and need to transfer to the hospital was low (0.1%) and did not correlate to anemia severity (p = 0.25). There was an increased incidence of non-sustained SVT or atrial fibrillation with moderate anemia and increased incidence of hypotension with stress testing with mild and moderate anemia. There was a significant reduction in duration of exercise (p &lt; 0.001) and METS (p &lt; 0.001) achieved with worsening anemia. Conclusion Our study demonstrates that exercise stress testing is safe in patients with mild and moderate anemia, albeit with reduced exercise capacity. Low numbers of severely anemic patients despite a large study population limit generalizability of these results in this group. Exercise Capacity Severe Anemia (N = 9) Moderate Anemia (N = 332) Mild Anemia (N = 1183) Non-anemic (N = 14128) P value Resting heart rate 81 ± 13 # 79 ± 14 # 72 ± 14 74 ± 13 &lt;0.001* Peak heart rate 148 ± 22 139 ± 24 # 138 ± 23 # 147 ±22 &lt;0.001* Exercise duration 5.3 ± 2.5 # 6.3 ± 2.1 # 7.2 ± 2.5 # 8.6 ± 2.7 &lt;0.001* METS 6.3 ± 2.5 # 7.1 ± 2.2 # 8.0 ± 2.5 # 9.5 ± 2.7 &lt;0.001* Safety Hypotension with stress 0 (0%) 31 (9.4%) # 94 (8.0%) # 437 (3.1%) &lt;0.001* Mild supraventricular arrhythmia 1 (11.1%) 15 (4.5%) # 20 (1.7%) # 237 (2.3%) 0.04* Severe supraventricular arrhythmia 0 (0%) 0 (0%) 0 (0%) 7 (0.1%) 0.99 Mild ventricular arrhythmia 0 (0%) 20 (6.0%) 74 (6.3%) 756 (5.4%) 0.94 Moderate ventricular arrhythmia 0 (0%) 3 (0.9%) 13 (1.1%) 182 (1.3%) 0.78 Severe ventricular arrhythmia 0 (0%) 1 (0.3%) 2 (0.2%) 1 (0.0%) 0.02 Transfer to hospital 0 (0%) 2 (0.6%) 1 (0.1%) 9 (0.1%) 0.29 Any severe arrhythmia or hospitalization 0 (0%) 2 (0.6%) 3 (0.3%) 17 (0.1%) 0.25 # Multi-comparison adjusted P-value &lt;0.05 compared to non-anemic when group P &lt; 0.05