Trial in Progress: Sonoporation for Disrupting the Pancreatic Cancer Microenvironment to Enhance Chemotherapy Delivery and Improve Outcomes
James Posey, John R. Eisenbrey, Babar Bashir, Patrick Mille, Atrayee Basu Mallick, Rajan Singla, Spiros Kotopoulis, Ingrid Nordaas, Audun Magerøy Trelsgård, Tæraneh Jouleh, Georg Dimcevski, Odd Helge Gilja, and Flemming Forsberg
- Pancreatic ductal adenocarcinoma (PDAC) is 3% of cancers diagnosed in the United States with 62,210 new cases expected in 2022, but it is the fourth leading cause of cancer-related deaths.
- Hence, there is a considerable clinical need to develop innovative strategies for effective drug delivery and treatment monitoring, resulting in improved outcomes for patients with PDAC.
- Sonoporation is a novel method that can enhance the therapeutic efficacy of co-administered chemotherapy by localized contrastenhanced ultrasound imaging (CEUS) of gas-filled microbubbles (ultrasound contrast agent UCA), which temporarily changes the tumor vascular microenvironment by increasing leakage from angiogenic vessels through microstreaming, shockwaves and the activation of various intracellular signaling responses .
- Our Phase I clinical trial of sonoporation in 10 PDAC patients treated with Gemcitabine demonstrated no additional toxicity and an increase in median survival compared to the standard of care treatment (8.9 vs 17.6 months; p = 0.011) .
- Subsequent, animal studies investigated 4 commercial UCAs under 2 different acoustic regimes and established the optimal UCA (Sonazoid; GE Healthcare, Oslo, Norway) as well as acoustic settings for sonoporation of PDAC .
- There are two major chemotherapeutic regimens for the treatment of non-resectable PDAC, a combination of Leucovorin, Fluorouracil, Irinotecan and Oxaliplatin (FOLFIRINOX), considered the first line treatment, or a combination of Gemcitabine with a nanoparticle formulation of Paclitaxel (Nab-Paclitaxel), the second line treatment. These regiments results in a median overall survival of approximately 11 and 8-9 months.
- The Oncological departments at Jefferson and Haukeland will be responsible for the SoC chemotherapeutic treatment. We will use the hospital’s standard recommended treatment protocols of gemcitabine hydrochloride (Gemkabi®) combined with nanoparticle albumin-bound paclitaxel (Nab-Paclitaxel (Abraxane®)), and FOLFIRINOX.
Meaning-Centered Supervision: A Structured Self-Reflection Model to Reconnect with Personal and Professional Meaning in Palliative Care Work
Rebecca Cammy, MSW, LCSW
Meaning-centered supervision explores participant’s sense of meaning of past, present, and future personal and professional experiences. The series aims to reintegrate selfreflection into clinical practice through experiential exercises, homework journaling, and group discussion. Social workers develop a narrative around themes of professional attitude, living and creating work life, and connections with the social work profession. The goal is to help palliative care social workers create a sense meaning and purpose in their work as they develop their personal and professional identities. Additionally, the hope is to support supervisees through any concerns of burnout and compassion fatigue.
Early Evidence of Dose-dependent Pharmacodynamic Activity Following Treatment with SY-5609, a Highly Selective and Potent Oral CDK7 Inhibitor, in Patients with Advanced Solid Tumors
Kyriakos P. Papadopoulos, Manish R. Sharma, Erika Hamilton, Debra Richardson, Babar Bashir, Dejan Juric, Geoffrey Shapiro, Graeme Hodgson, Nan Ke, Anthony D'Ippolito, Liv Johannessen, Qing Kang-Fortner, Li Zhou, Maria Rosario, William Zamboni, Hina A. Jolin, Catherine Madigan, Michael J. Kelly, and David A. Roth
Breaking the Transportation Barrier: Enhancing Access to Cancer Treatment through Technology and Philanthropy
Rebecca Cammy, MSW, LCSW; Jodi Sandos, MSW, LCSW; and Stephanie Chapman, BS
Cancer patients face many obstacles and challenges after being diagnosed with cancer. Thomas Jefferson University Hospitals’ Sidney Kimmel Cancer Center (SKCC) has effectively eliminated transportation as a barrier to care for patients receiving cancer treatments such as chemotherapy and radiation. SKCC dedicates a full-time patient navigator to assess and connect patients with appropriate transportation resources based on location, insurance coverage, and mobility. The utilization of patient-focused transportation platforms, such as Uber Health, RoundTrip, and Ride Health have streamlined the process, while SKCC philanthropic funds have assisted with associated financial costs. As a result of these resources, oncology patients who would have ordinarily missed appointments due to lack of transportation are now more independent and compliant with cancer treatment.
Impact of Palliative Care Consultation on End of Life Care Measures: A Retrospective Analysis of Patients in the Oncology Care Model
Alison Greidinger, MD; Maria Vershvovsky, MD; Evan Lapinsky, MD; Alison Rhoades, MD; Amy Leader, DrPH; Vittorio Maio, PharmD; Jared Minetola; Karen Walsh, MS, MBA; Valerie Csik, MPH, CPPS; and Ruben Rhoades, MD
- In 2016 ASCO recommended that patients with advanced cancer receive dedicated palliative care (PC) services1. Early PC involvement is associated with lower spending, fewer 30-day readmission rates, decreased chemotherapy administration at the end of life (EOL) and increased hospice referrals2.
- Many patients are not referred and continue to receive chemotherapy and utilize high-acuity services near the EOL.
- The Oncology Care Model (OCM) is a CMS episode-based alternative payment model promoting high-value care.
- We evaluated the effect of PC visits on EOL outcomes including code status (CS) and spending in the last 30 days of life.
Improving the Quality of Patient-Provider Interactions and Promoting Equitable, Accessible and Patient-Centered Cancer Care
C. Vaughan-Briggs, LCSW; A. Petok, LCSW, MPH; T. DeJesse; and Amy Leader, DrPH, MPH
- Philadelphia is among the top 10 cities in the US with populations over 500,000 with a high Community Need Index score (CNI- severity of Health disparity)
- Data from 2015 County Health Ranking, had Philadelphia last of all 67 counties in the state for social economic factors. (unemployment, income inequality, injury deaths, etc. )
- Cancer is a leading cause of mortality in the US
- The SKCC participated in a year-long, externally supported self study to improve the quality of patientprovider interactions and promote more equitable, accessible and patient- centered cancer care. This program aligned with internal initiatives.
- SKCC at Jefferson is NCI-designated cancer center and part of an academic medical center located in Philadelphia. In the catchment area the Incidence and Mortality in 7 out of 10 Major Cancers is higher than state and national averages.
A. Petok, MSW, MPH; G. Garber, MSW; L. Waldman, BA; A. Leader, PhD; A. Dicker, MD, PhD; and L. Capparella, MSS
- With an increase in and rapid development of health care applications, as well as electronic medical records and patient portals, patients have more access to health information than ever.
- Previous research has found an association between integration of electronic patient reported outcomes (ePROs) with increased survival for patients with metastatic cancer compared to usual care.
- Although greater access to health information as well as personal health records and patient portals can be shown to have positive effects on patient outcomes, the digital divide that is pervasive in the general population extends to oncology as well.
- This project aimed to determine the differences in patient interest in and usage of technology for health care amongst various demographics.
Optimizing Psychosocial Care of Older Adults with Cancer: An Early Assessment and Intervention Model
Lora Rhodes, LCSW and Andrew Chapman, DO, FACP
Jefferson Multidisciplinary Senior Adult Oncology Center
- Established September 2010
- First multidisciplinary geriatric oncology evaluation center in the tristate area
- 890 patients evaluated to date
- All tumor types
- Age 70 and above & Pre-transplant (Bone Marrow) evaluation age 65 and above
- Consultative service
- Two sessions weekly
- Average evaluation time: two hours
- Navigator, Medical Oncologist, Geriatrician, Pharmacist, Nutritionist, Social Worker
- As needed: Psychiatry, Rehab Medicine, Radiation Oncology, Surgery
Lisa M. Capparella, MSS, LCSW, OSW-C and S. Otis-Green, MSW, MA, ACSW, LCSW, OSW-C
- Life Review Videos can provide patients with hope, help them finding meaning and value of life.
- Patients with cancer have limited opportunities to discuss their life before cancer.
- Insufficient research related to how patients would want their video to be used by family/friends and who they would chose to share their video with.
- Limited research regarding whether the relationship with the interviewer matters to participants of life review.
Safety of Lobar Hepatic Arterial Embolization in Metastatic Uveal Melanoma Patients with Underlying Gilbert's Disease
David C. Feldstein, MD; Robert D. Adamo, MD; Carin F. Gonsalves, MD, FSIR; David J. Eschelman, MS, FSIR; Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA; and Takami Sato, MD, PhD
❖ Uveal melanoma is the most common primary intraocular malignant tumor in adults.
❖ Up to half of all patients develop systemic metastases, with liver involvement in >90% of patients.1
❖ Various liver-directed, locoregional therapies (i.e. chemoembolization, immunoembolization, radioembolization, and ablation) have played a significant role in prolonging the lives of patients with metastatic uveal melanoma.2
❖ Elevated bilirubin levels are typically considered a relative contraindication for lobar hepatic arterial embolization treatment, given mainly the increased risk of precipitating hepatic failure.
❖ Gilbert's syndrome, also known as benign unconjugated hyperbilirubinemia, is a hereditary disorder of bilirubin conjugation. Gilbert’s syndrome leads to elevated levels of serum bilirubin, that do not truly reflect cholestasis or liver failure and therefore should not exclude patients from targeted embolization therapy.3
Poster presented at: World Conference on Interventional Oncology in Boston MA.
Ryan M. Weight, Shingo Sato, Masahiro Ohara, Mizue Terai, Michael Mastrangelo, Marlana Orloff, Benjamin Goldschmidt, John Viator, and Takami Sato
Circulating tumor cells (CTCs) have been shown to be a prognostic marker in breast cancer1. We hypothesize that circulating melanoma cell (CMC) detection could be utilized in the management of uveal melanoma, including early intervention. Prior methodologies for circulating uveal melanoma cell (CUMC) detection have been fraught with poor sensitivity, limiting their clinical utility2. Development of an improved method is necessary to establish the clinical utility of CUMC monitoring. Photoacoustics, also referred to as laser-induced ultrasound, is a novel platform for the detection and capture of CMCs. Photoacoustics uses short duration pulsed light to create ultrasonic acoustic waves in an optically absorbing medium, in this case melanin within melanoma3. As light is absorbed by irradiated chromophores, the optical energy gets converted into kinetic thermal energy trapped within the chromophore and subsequent thermal expansion ensues. Transient thermoelastic expansion of the absorbent cell results in the propagation of ultrasonic acoustic waves which can be detected and analyzed using a piezoelectric response mechanism. In addition, detected CMCs can be isolated by a two-phase flow cell separation technique4. Due to the low cost and melanoma specific capabilities of photoacoustics, we evaluated this technology for the purpose of CUMC detection.
Methods: Cells from uveal melanoma cell line UM002B, established at Thomas Jefferson, were titrated to various cell concentrations and analyzed in a neutral density solution utilizing the photoacoustic method. Uveal melanoma cells of differing concentrations were spiked into isolated healthy donor peripheral blood mononuclear cells (PBMCs) and healthy whole blood samples. PBMC isolates were analyzed for CUMCs.
Results: CUMCs were successfully quantified by the photoacoustic method including single cell detection. Recovery rates of cultured cells in a neutral density solution approached 25%. Recovery rates for CUMCs in whole blood averaged 10% of expected cell yield (56/540 cells detected) with a higher detection rate at lower cell concentrations. Photoacoustics offers a viable method for the detection of CUMCs with an accuracy that meets or exceeds previously reported CUMC yields. Studies analyzing CUMCs from patients with metastatic disease are ongoing.
Metabolic Patterns in Cancer Cells and Tumor Micro-environment in Diffuse Large B¬Cell Lymphoma: Tumor–Stromal Metabolic Coupling
Mahasweta Gooptu, MD; Alina E. Dulau Florea, MD; Benjamin E. Leiby, PhD; Barbara Pro, MD; John David Sprandio, Jr. MD; Diana Whitaker-Menezes, PhD; Paolo Cotzia, MD; Guldeep Uppal, MD; Jaime Caro, MD; Jerald Z. Gong, MD; and Ubaldo E. Martinez-Outshoorn, MD
It has previously been suggested that the tumor microenvironment in diffuse large B-cell lymphoma (DLBCL) has prognostic significance. Furthermore, gene expression profiling in DLBCL patients has identified separate subsets with glycolytic and mitochondrial (oxidative phosphorylative) metabolic signatures.
Glycolytic metabolism forms the basis for FDG PET scans, widely used in staging and response assessment in DLBCL. While many assume that the tumor as a whole is primarily glycolytic, the metabolic patterns of cancer cells (C) and surrounding cancer-associated stromal cells (CAS) remain relatively unknown. We investigated the in situ metabolic patterns of C and CAS cells as well as tumor-associated macrophages (TAM) in DLBCL.
Hee-Soon Juon, PhD; Frederic Kim, MS; Seon Yoon Chung, MSN; and Sunmin Lee, ScD
To report the prevalence of Health Related Quality of Life (HRQOL) in foreign-born Asian Americans (AA) and to compare this with the general AA from 2010 BRFSS data.
To examine the influential factors associated with HRQOL-4 including English proficiency, perceived racial discrimination, smoking, alcohol use, and sociodemographics.
Quality of life (QOL) represents individuals’ subjective perception of multidimensional aspects of life including physical, psychological, social and spiritual aspects.
HRQOL represents the physical and mental health domain of QOL.
Centers for Disease Control and Prevention (CDC) has been measuring HRQOL to capture people’s overall perceptions about their health; HRQOL has become an important component of health surveillance (U.S. DHHS, 2000).
While acculturation and racial discrimination have been negatively associated to the number of chronic health conditions and well-being of AA, their influence on HRQOL has not been studied.
Public surveillance study has typically considered Asian Americans as a single group and little is known about how HRQOL and health-related risk factors vary among foreign-born Asian Americans including Chinese-, Korean-, and Vietnamese- Americans.
Poster presented at APHA in Chicago Illinois.
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