Showing papers by "Eric Henderson published in 2019"

Review of clinical trials in intraoperative molecular imaging during cancer surgery.

Abstract: Most solid cancers are treated by surgical resections to reduce the burden of disease. Surgeons often face the challenge of detecting small areas of residual neoplasm after resection or finding small primary tumors for the initial resection. Intraoperative molecular imaging (IMI) is an emerging technology with the potential to dramatically improve cancer surgery operations by allowing surgeons to better visualize areas of neoplasm using fluorescence imaging. Over the last two years, two molecular optical contrast agents received U.S. Food and Drug Administration approval, and several more drugs are now on the horizon. Thus a conference was organized at the University of Pennsylvania to bring together oncologic surgeons from different specialties to discuss the current clinical status of IMI trials with a specific focus on phase 2 and phase 3 studies. In addition, phase 1 and experimental trials were also discussed briefly, to highlight other novel techniques. Our review summarizes the discussions from the conference and delves into the types of cancers discussed, different contrast agents in human trials, and the clinical value being studied.

Preclinical imaging of epidermal growth factor receptor with ABY-029 in soft-tissue sarcoma for fluorescence-guided surgery and tumor detection.

Abstract: Background and objectives Fluorescence-guided surgery using epidermal growth factor receptor (EGFR) targeting has been performed successfully in clinical trials using a variety of fluorescent agents. We investigate ABY-029 (anti-EGFR Affibody® molecule labeled with IRDye 800CW) compared with a small-molecule perfusion agent, IRDye 700DX carboxylate, in a panel of soft-tissue sarcomas with varying levels of EGFR expression and vascularization. Methods Five xenograft soft-tissue sarcoma cell lines were implanted into immunosuppressed mice. ABY-029 and IRDye 700DX were each administered at 4.98 μM. Fluorescence from in vivo and ex vivo (fresh and formalin-fixed) fixed tissues were compared. The performance of three fluorescence imaging systems was assessed for ex vivo tissues. Results ABY-029 is retained longer within tumor tissue and achieves higher tumor-to-background ratios both in vivo and ex vivo than IRDye 700DX. ABY-029 fluorescence is less susceptible to formalin fixation than IRDye 700DX, but both agents have disproportional signal loss in a variety of tissues. The Pearl Impulse provides the highest contrast-to-noise ratio, but all systems have individual advantages. Conclusions ABY-029 demonstrates promise to assist in wide local excision of soft-tissue sarcomas. Further clinical evaluation of in situ or freshly excised ex vivo tissues using fluorescence imaging systems is warranted.

Measuring microdose ABY-029 fluorescence signal in a primary human soft-tissue sarcoma resection.

Abstract: Near-infrared (NIR) fluorescence combined with targeting epidermal growth factor receptor (EGFR) overexpression for surgical guidance in many cancers is gaining momentum. ABY-029 is an anti-EGFR Affibody molecule conjugated to IRDye 800CW that is FDA approved as an exploratory Investigational New Drug (eIND 122681). ABY-029 has a short plasma half-life (~15-20 minutes), which allows for administration of the imaging agent and excision surgery to occur on the same day unlike fluorescent antibodies. This fast tissue clearance may provide the means necessary to achieve clinically relevant tumor-to-normal tissue contrast levels using microdosing administration schemes. Pre-clinical studies have indicated that tumor-to-normal tissue contrast peaks between 4-8 hours depending on EGFR expression. Additionally, the No Observable Adverse Effect Level (NOAEL) was determined in pre-clinical toxicity studies to be 1,000X the microdose, or 30 micromole, whereas mild adverse events are common in antibody imaging studies. A number of promising first-in-human clinical Phase 0 trial microdose evaluation of ABY-029 have been initiated for recurrent glioma, soft-tissue sarcoma, and head and neck cancers (NCT0290925, NCT03154411, and NCT03282461, respectively). Here, we provide an update on our experience using ABY-029 for surgical resection at microdose levels and describe tissue contrast and correlation of ABY-029 fluorescence to EGFR tissue expression. Current progress indicates that moderate TBRs (~3-5) are observable at the microdose administration level but increased administration doses (3X and 6X microdoses) are being investigated. In addition, ex vivo tissue fluorescence is highly correlated to EGFR staining in both intensity and spatial localization.

Duration of military service is associated with decision quality in Veterans considering total knee replacement: case series.

Abstract: Purpose Due to the nature of military service, the patient-physician relationship in Veterans is unlike that seen in civilian life. The structure of the military is hypothesized to result in barriers to open patient-physician communication and patient participation in elective care decision-making. Decision quality is a measure of concordance between a chosen treatment and the aspects of medical care that matter most to an informed patient; high decision quality is synonymous with patient-centered care. While past research has examined how age and other demographic factors affect decision quality in Veterans, duration of military service, rank at discharge, and years since discharge have not been studied. Patients and methods We enrolled 25 Veterans with knee osteoarthritis at a VA hospital. Enrollees completed a survey with demographic, military service, and decision-making preference questions and the Hip-Knee Decision Quality Instrument (HK-DQI), which measures patients' knowledge about their disease process, concordance of their treatment decision, and the considered elements in their decision-making process. Results The HK-DQI knowledge score had a significant, positive correlation with duration of military service (R2=0.36, p=0.004). Rank at discharge and years since discharge did not show a significant correlation with decision quality (p=0.500 and p=0.317, respectively). The concordance score did not show a statistically significant correlation with rank, duration of service, and years since discharge (p=0.640, p=0.486 and p=0.795, respectively). Additionally, decision process score was not significantly associated with rank, duration of military service, and years since discharge (p=0.380, p=0.885, and p=0.474, respectively). Conclusion Decision quality in Veterans considering treatment for knee osteoarthritis appears to be correlated positively with duration of military service. These findings may present an opportunity for identification of Veterans at most risk of low decision quality and customization of shared decision-making methods for Veterans by characteristics of military service.

Comparison of detection sensitivity of near infrared (NIR) surgical imaging systems using a connective tissue phantom model.

Abstract: Many tumors for which fluorescence guided surgery (FGS) has been developed are surface tumors, where direct visualization by the surgeon is straightforward. On the other hand, cancers such as soft-tissue sarcomas, are present at a subsurface level. Resection of these sub-surface tumors is performed using 'wide local excision' where a single, complete mass is removed with an intact zone of normal tissue (~ 1 cm 'margin'). We used a phantom model for sarcoma with near infrared fluorophore IRDye800 CW that defined different tissue properties. We compare the detection sensitivity of two commercially available near infrared (NIR) surgical imaging systems, Solaris (Perkin Elmer) and SPY PHI (Novadaq) using the phantom models of sarcoma. We also determine targeted fluorescence signal on both systems for blinded surgical phantom dissection by a surgeon. The fluorescence intensities are higher for Solaris than for SPY-PHI. On average, the fluorescence increased with an increase in intralipid concentration and decreased with an increase in blood concentration. The depth of imaging was higher for Solaris than for SPY PHI. Using the target values, the surgeon successfully dissected all phantoms using Solaris. Using fat phantoms for SPY PHI, the surgeon cut through four out of the total. Further improvement in FGS will improve cancer recurrence and morbidity.

Trajectory and aiming guide for use with fluoroscopy

Abstract: A system for a trajectory and aiming guide for use with fluoroscopy is comprised of a ring holder is with a plurality of connecting arms, a radiolucent ring disk with an outer perimeter wall and a central axle on the bottom surface of the ring disk; a first rotatable disk located below the ring holder and comprised of a handle, a radiolucent disk ring with a central cutout to receive the central axle, the material of the disk comprising an embedded array of a plurality of radiopaque wires and an outer perimeter wall; a second rotatable disk located below the first rotatable disk and comprised of a handle, a radiolucent disk ring with a central cutout to receive the central axle, the material of the disk comprising an embedded array of a plurality of radiopaque wires and an outer perimeter wall; and a locking cap for the axle.

ON SURGICAL FAILURES: Onward to objective evaluation of our less proud moments

Abstract: In recent years a spate of popular writing has focused on the merits of failure (1-6). In various forms, failure is approached from the perspectives of parents (let your children fail!), leaders (allow your employees to fail!), and self-help (let yourself fail and learn from it!). One of my favorite coffee brands states plainly on its container that “things that matter in life” include “never being afraid to fail”. Failure is chic, failure is trending! Twenty years ago, my university commencement speaker orated the experiential virtues of failure as being essential to our growth as individuals and as a society. ‘So, get out there and fail!’ he concluded with gusto. He was not a physician—he taught history.