Day 1 :
The University of Texas Medical Branch, USA
Keynote: Neuroendocrine carcinoma of the gynecologic tract: Presentation, prognosis and treatment response
Time : 09:40-10:20
Sandra S. Hatch has been a faculty physician with UTMB for over ten years, specializing in breast and gynecological cancers. She is board certified in Radiation Oncology by the American Board of Radiology (ABR) and an active member with the American Society for Therapeutic Radiology & Oncology (ASTRO). She received her doctorate in medicine from the University of Texas Health Science Center at Houston, TX and completed her residency in radiation therapy at Baylor College of Medicine as chief resident. Before entering medical school, Dr. Hatch received her degree in engineering from Tennessee Technological University, which served as a solid foundation for the technological demands found in the field of radiotherapy.
Purpose: Neuroendocrine carcinoma is a rare malignancy of the cervix and uterus representing a therapeutic challenge due to heterogeneity of cell type and lack of consensus standardized treatment. The purpose of this study is to use the SEER database to evaluate the presentation, prognosis, treatment patterns and survival.rnMethods: Subtypes included: small cell (SC), large cell (LC) and carcinoid (CD). Inclusion criteria were known record of staging and treatment history of radiation (RT) and/or surgery. Kaplan-Meier and Cox regression analyses were utilized to evaluate overall survival (OS) and specific survival (SS) analysis. Patients diagnosed 2004-2012; staging with TNM AJCC 6th edition to derive FIGO staging or SEER summary staging.rnResults: 147 uterus: 60 (41%) SC, 19 (13%) LC, 68 (46%) CD. Median follow up 40 months. FIGO stage was not available for 74 (50%); SEER summary stage utilized: local 22 (15%), regional 56 (39%), distant 65 (45%). 2 year SS: 67% (local), 57% (regional), 27% (distant). Surgery only 65 (44%), radiation only 14 (10%), surgery and radiation 27 (18%) and neither 41 (28%). NSD of OS (9m) between histologies. 20 with local group stage, addition of radiation to surgery with trend for increased 3-year SS (88 vs 62%, p=0.17). 11 receiving adjuvant radiation, brachytherapy only cases had non-statistically better 3-year OS (100 vs 67%, p=0.30) and SS (100 vs 83%, p=0.56). 56 patients with regional disease, addition of radiation to surgery increased 3-year OS (71 vs 33%, p=0.01) although NSD for SS (71 vs 46%, p=0.18). 311 cervix. Median follow up 14 months; 194 SC, 28 LC & 89 CD. Staging 45% N0M0, 24% N1M0 and 31% M1. Probability of LN+ by T stage: T1 (18%), T2 (35%), T3 (29%), T4 (16%); probability of DM: T1 (16%), T2 (36%), T3 (51%), T4 (63%). CD greater LN- compared to SC (64 vs 49% respectively, p=0.02), LC trended higher metastases compared to SC & CD (46 vs 30 vs 29%, respectively, p=0.09 & 0.08). FIGO Stage I treated surgery alone better OS (3-year: 74 vs. 43%, p=0.003) similar SS (78 vs 64%, p=0.52) to treated with radiation alone. FIGO Stage I CD more with surgery alone than SC (60 vs 30%); less definitive (6 vs 25%) or adjuvant (28 vs 39%) radiation (p=0.001 for all). SC had superior OS with surgery alone over RT alone (p<0.001); CD had similar survival with surgery or RT. FIGO Stage III LC more frequently managed with surgery alone than SC (50 vs 4%, p=0.02) and less likely to receive definitive radiation (0 vs 75%, p=0.03). FIGO Stage IVB LC less likely to receive radiation alone than SC (8 vs 52%, p=0.003). Cox multivariate analysis showed improved OS & SS with brachytherapy boost to external beam (HR=0.54, p<0.03 for both) among stage and age related prognostic factors, while histology was not significant.rnConclusion: Noting potential for selection bias in this retrospective cohort, as well as chemotherapy not available, future combined modality approach is required to enhance the management of neuroendocrine carcinoma of the uterus and the cervix. rn
AccuTheranostics, Inc, USA
Keynote: The necessity to stratify gynecologic patients in-vitro prior to in-vivo treatment modalities
Time : 10:20-11:00
Sherry Bradford attended undergraduate school at SUNY at Buffalo and was awarded a full tuition scholarship to pursue her PhD graduate degree (Biochemistry) from the University of Buffalo/ Roswell Park Cancer Institute Division of SUNY at Buffalo School of Medical and Biomedical Sciences. There she successfully led the research on the use of human micro vascular umbilical cord endothelium for lining stents. It was while Sherry was at Millard Fillmore Hospital, that she was awarded the “1st Place - Award for Excellence in Research” from the American Federation for Clinical Research In 1997. In 2008, Dr Bradford and colleagues form AccuTheranostics and the idea on Oncology Personalized Medicine based on the specific patient’s own biochemical and genetic profile to administer Personalized treatment regimens.She is also a member of many professional organizations including (but not limited to): International Metabolic Cancer Group, AACR, ASCO, and GLIFCA.
Cancer remains one of the most challenging diseases to treat. This, in part, is due to the heterogeneity of tumors. Most cancers are monoclonal in origin, however, due to innate genetic instability subsequent cell generations take on new characteristics. But, tumors cells are not the only contributors of tumor heterogeneity, the entire microenvironmental constituents and its non-tumorous cells have an absolute influence as well. Thus, there exists a reciprocal and dynamic interaction between tumor cells, microenvironment constituents and non-tumorous cells that produce a well-defined individualistic tumor phenotype. The clinical relevance is that the tumor and its microenvironment heterogeneity contribute significantly to the efficacy of drug therapy. Also, transporter genetic variants cause population-specific differences in drug transport and therefore impart considerable inter-individual variation in pharmacotherapy and thus clinical response to a myriad of agents. This divergence underscores the necessity of personalized medicine wherein the data garnered from a person’s own cancer is utilized to develop a highly individualized therapeutic regimen. Our lab briefly delineates a reliable in-vitro test that employs a more scientific and logical approach to identify drug(s) and drug combinations that may be efficacious against a specific patient’s tumor in-vivo. The patient’s own tumor mass is fully disaggregated and as such, all cells (microenvironment) that compose the tumor are subjected to cytotoxic/cytolytic agents. The end-point is cell death (not cell-growth), which correlates to clinical outcomes. Albeit, the entirety our data is not shown our gynecologic studies validate that in-vitro testing does qualify as a tool that can assist and guide oncologists to the most efficacious therapy(s) for their patients. While the heterogeneity of tumor types and its microenvironment, validates the necessity to individualize chemotherapy, a randomized controlled clinical trial must be designed to further correlate and validate our studies and to fully appreciate the impact of in-vitro chemoresistance and sensitivity testing on cancer recurrence and survival rates.