Jefferson Digital Commons quarterly report: January-March 2020

This quarterly report includes: New Look for the Jefferson Digital Commons Articles COVID-19 Working Papers Educational Materials From the Archives Grand Rounds and Lectures JeffMD Scholarly Inquiry Abstracts Journals and Newsletters Master of Public Health Capstones Oral Histories Posters and Conference Presentations What People are Saying About the Jefferson the Digital Common

Review of precision cancer medicine: Evolution of the treatment paradigm.

In recent years, biotechnological breakthroughs have led to identification of complex and unique biologic features associated with carcinogenesis. Tumor and cell-free DNA profiling, immune markers, and proteomic and RNA analyses are used to identify these characteristics for optimization of anticancer therapy in individual patients. Consequently, clinical trials have evolved, shifting from tumor type-centered to gene-directed, histology-agnostic, with innovative adaptive design tailored to biomarker profiling with the goal to improve treatment outcomes. A plethora of precision medicine trials have been conducted. The majority of these trials demonstrated that matched therapy is associated with superior outcomes compared to non-matched therapy across tumor types and in specific cancers. To improve the implementation of precision medicine, this approach should be used early in the course of the disease, and patients should have complete tumor profiling and access to effective matched therapy. To overcome the complexity of tumor biology, clinical trials with combinations of gene-targeted therapy with immune-targeted approaches (e.g., checkpoint blockade, personalized vaccines and/or chimeric antigen receptor T-cells), hormonal therapy, chemotherapy and/or novel agents should be considered. These studies should target dynamic changes in tumor biologic abnormalities, eliminating minimal residual disease, and eradicating significant subclones that confer resistance to treatment. Mining and expansion of real-world data, facilitated by the use of advanced computer data processing capabilities, may contribute to validation of information to predict new applications for medicines. In this review, we summarize the clinical trials and discuss challenges and opportunities to accelerate the implementation of precision oncology

Practical guidance for applying the ADNEX model from the IOTA group to discriminate between different subtypes of adnexal tumors.

All gynecologists are faced with ovarian tumors on a regular basis, and the accurate preoperative diagnosis of these masses is important because appropriate management depends on the type of tumor. Recently, the International Ovarian Tumor Analysis (IOTA) consortium published the Assessment of Different NEoplasias in the adneXa (ADNEX) model, the first risk model that differentiates between benign and four types of malignant ovarian tumors: borderline, stage I cancer, stage II-IV cancer, and secondary metastatic cancer. This approach is novel compared to existing tools that only differentiate between benign and malignant tumors, and therefore questions may arise on how ADNEX can be used in clinical practice. In the present paper, we first provide an in-depth discussion about the predictors used in ADNEX and the ability for risk prediction with different tumor histologies. Furthermore, we formulate suggestions about the selection and interpretation of risk cut-offs for patient stratification and choice of appropriate clinical management. This is illustrated with a few example patients. We cannot propose a generally applicable algorithm with fixed cut-offs, because (as with any risk model) this depends on the specific clinical setting in which the model will be used. Nevertheless, this paper provides a guidance on how the ADNEX model may be adopted into clinical practice

A lab-on-a-disc platform enables serial monitoring of individual CTCs associated with tumor progression during EGFR-targeted therapy for patients with NSCLC

Rationale: Unlike traditional biopsy, liquid biopsy, which is a largely non-invasive diagnostic and monitoring tool, can be performed more frequently to better track tumors and mutations over time and to validate the efficiency of a cancer treatment. Circulating tumor cells (CTCs) are considered promising liquid biopsy biomarkers; however, their use in clinical settings is limited by high costs and a low throughput of standard platforms for CTC enumeration and analysis. In this study, we used a label-free, high-throughput method for CTC isolation directly from whole blood of patients using a standalone, clinical setting-friendly platform. Methods: A CTC-based liquid biopsy approach was used to examine the efficacy of therapy and emergent drug resistance via longitudinal monitoring of CTC counts, DNA mutations, and single-cell-level gene expression in a prospective cohort of 40 patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Results: The change ratio of the CTC counts was associated with tumor response, detected by CT scan, while the baseline CTC counts did not show association with progression-free survival or overall survival. We achieved a 100% concordance rate for the detection of EGFR mutation, including emergence of T790M, between tumor tissue and CTCs. More importantly, our data revealed the importance of the analysis of the epithelial/mesenchymal signature of individual pretreatment CTCs to predict drug responsiveness in patients. Conclusion: The fluid-assisted separation technology disc platform enables serial monitoring of CTC counts, DNA mutations, as well as unbiased molecular characterization of individual CTCs associated with tumor progression during targeted therapy

Needs Assessment for a Patient Centered Medical Home Model of Care at the Providence Alaska Cancer Center

Presented to the Faculty of the University of Alaska Anchorage in Partial Fulfillment of the Requirements for the Degree of MASTER OF PUBLIC HEALTHIn order to better understand the needs of cancer patients and allocate resources, the Providence Alaska Cancer Center requested a needs assessment for an oncology focused patient centered medical home (PCMH). A PCMH allows for coordinated and comprehensive care through the use of a teamwork model that centers on the primary care physician. The Providence Alaska Cancer Center staff randomly selected the records of 200 cancer patients between 2010 and 2011, using the cancer tumor registry. Data were analyzed to answer four specific questions that addressed the 1) presence of a Primary Care Physician (PCP), 2) number and type of comorbidities, 3) cancer diagnosis and 4) insurance status impacted emergency room utilization. Individuals tended to utilize the emergency room more if they 1) had a PCP, 2a) had three or more comorbidities, 2b) were diagnosed with hyperlipidemia, chronic obstructive pulmonary disease (COPD) or hypertension, 3) were diagnosed with an “other” cancer as opposed to breast, lung or gynecological cancers or 4) had federal insurance. These data in particular show expected trends such as patients who have more medical complications have higher emergency room utilization rates than patients with less complicated medical history and that certain comorbidities (hyperlipidemia, hypertension and chronic obstructive pulmonary disease) may be predictors of emergency room utilization. These trends may allow providers to create more specialized treatment and care plans for patients at greater risk of emergency room utilization.Signature Page / Title Page / Abstract / Table of Contents / List of Figures / List of Tables / List of Appendices / Introduction to Cancer and its Treatment / Introduction to the Patient Centered Medical Home Model / Treatment of Cancer in Alaska / Study Goals, Rationale, Research Questions and Hypotheses / Methods / Sample Demographics and Description / Results and Discussion / Strengths and Limitations / Future Directions / References / Appendice

Cancer Niche as a Garbage Disposal Machine: Implications of TCM-Mediated Balance of Body-Disease for Treatment of Cancer.

Cancer epidemic led to worldwide to search for a new "game changer" concept to govern cancer research and cancer treatment. Western medicine-based cancer research has been extending the impasse without resolution in sigh for improving survival of patients with solid malignant tumors in the last four decades due to heterogeneity in cancer tissues. Such a deadlock charts a course to learn lessons from the developing countries, directly or indirectly to complement the exhausted Western medicine. We propose a new concept of "Cancer niche as a garbage disposal machine" with implications of traditional Chinese medicine-mediated restoration of normal balance between body and disease to bring the fight against cancer under control

Laparoscopic resection of gastric GISTs. Where do we stand now? A single-centered experience

Introduction. Gastrointestinal stromal tumors (GISTs) represent a rare type of gastrointestinal neoplasms. Resection with negative margins has been established as a mainstay treatment, but laparoscopic resections are still open to debate. Material and method. This retrospective study was conducted at a single institution, with data collected over 2 years (01.01.2017-01.01.2019). The variables examined were age, tumor location with regard to the gastric wall, the results of the intraoperative endoscopy, intraoperative and postoperative complications, the surgical technique, and histopathological reports. Results. We identified 12 relevant cases, of which 8 were females and 4 males. The average tumor diameter was 2.3 cm. The majority of the lesions were located on the anterior gastric wall (8 cases), on the small curvature (2 cases), and in the pyloric region (2 cases). Intraoperative endoscopy was performed successfully in 10 cases in order to identify the lesions and guide the resection. The average operative time was 120 minutes and the average hospital stay was 5 days. The gastric wall with the lesion was resected using an Ultrasonic device, a 2-cm oncological safety margin was preserved. Conclusion. Complete surgical resection independent from the tumor size represents the current optimal treatment. From a surgical point of view, these tumors must be considered malignant and the surgeon must respect principles of oncological surgery. Maintaining tumor integrity at dissection is critical for the patient’s long-term prognosis. Laparoscopic resection independent of the tumor size is feasible