Day 1 :
Keynote Forum
Sandra S. Hatch
The University of Texas Medical Branch, USA
Keynote: Neuroendocrine carcinoma of the gynecologic tract: Presentation, prognosis and treatment response
Time : 09:40-10:20
Biography:
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.
Abstract:
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
Keynote Forum
Sherry Bradford
AccuTheranostics, Inc, USA
Keynote: The necessity to stratify gynecologic patients in-vitro prior to in-vivo treatment modalities
Time : 10:20-11:00
Biography:
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.
Abstract:
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.
Keynote Forum
Hani Gabra
Imperial College London, UK
Keynote: OPCML, a systems regulator of receptor tyrosine kinases in ovarian and other cancers
Time : 9:30-10:00
Biography:
Hani Gabra is Professor and Head of Medical Oncology, Deputy Head of the Division of Cancer and Director of the Ovarian Cancer Action Research Centre at Imperial College. He is also Associate Director and Lead of the Cancer Division (Division 1) of the NIHR Clinical Research Network for North West London
Abstract:
OPCML, a GPI anchored tumor suppressor gene is inactivated by somatic methylation in multiple cancers. We demonstrated inactivation by LOH and somatic methylation in 80% of ovarian cancers. We showed that OPCML is a strong in-vivo tumor suppressor in SKOV-3 and PEO1 ovarian cancer cell lines with no expression of OPCML. We demonstrated that OPCML negatively regulates a specific repertoire of receptor tyrosine kinases (RTKs) including EPHA2, FGFR1, HER2 and AXL with no effect on other RTKs e.g., VEGFR1 and VEGFR3. shRNA knockdown of OPCML accelerates the growth of normal ovarian surface epithelial cells in vitro. Immunoprecipitation revealed that OPCML binds to EphA2, FGFR1, HER2 and AXL extracellular domains with no such interaction to EGFR, thus OPCML binds directly to RTKS that it negatively regulates. We demonstrated that OPCML is located exclusively in the raft membrane fraction and sequesters RTKs that it binds to the raft fraction. We demonstrate that OPCML abrogates EGF and Gas 6 mediated phosphorylation of FGFR1, HER2 and AXL and the downstream phosphosignaling of pErk and pAKT. A recombinant modified OPCML-like protein without a GPI anchor caused inhibition of wound healing assay and tumorigenicity in skov3. In summary, the OPCML tumor suppressor mediates its suppressor function on the external leaflet of the plasma membrane by systems level negative regulation of at least 5 RTKs, and a recombinant modified derivative biotherapy is a potent tumor suppressor protein therapeutic in-vitro and in-vivo that recapitulates the in-vitro mechanism
Keynote Forum
Elisabeth Wikstrom Shemer
Karolinska Institute,Sweden
Keynote: Evaluation of a portable field colposcope in a non-cytology based cervical cancer screening program
Time : 10:00-10:30
Biography:
Elisabeth Wikström Shemer is a Senior Consultant of Obstetrics and Gynecology and affiliated with Department of Clinical Sciences, Karolinska Institute, Stockholm, Sweden. Dr. Wikström Shemers\' research focus on cervical cancer, colposcopy and improving screening methods to the underserved as well as intrahepatic cholestasis pf pregnancy. She has also invented a small. portable, battery-driven colposcope, the Gynocular to improve access to colposcopy. Dr. Wikström Shemer has been awarded the SKAPA prize for the invention of the Gynocular, Stockholm Stads innovations stipendium 2010, the Red Dot award 2013, as well as Vinnova 2009 and 2014 for developing digital health and the 33-list 2015 award. She is and MD, Ph.D in Obstetrics and Gynecology from the Karolinska Institute, Stockholm Sweden and serves as Gynius\' Medical Director
Abstract:
Objectives: After the introduction of non cytological tests like visual inspection after acetic acid (VIA) or Human Papillomavirus (HPV) test, there is a paradigm shift in screening for cervical cancer. Though ‘screen and treat’ strategy is being recommended in low resource settings, the low positive predictive values of both the tests will lead to lot of overtreatment. GynocularTM is a battery-operated, portable device with three-step magnification and green-filter. Present study was conducted in a community setting to evaluate GynocularTM in detection of cervical neoplasias.rnrnMethodology: Women between 30-60 years were screened using VIA and HPV test. Women positive on either test had evaluation by GynocularTM using IFCPC 2011 colposcopy classification and swede score. Punch biopsy was obtained from any lesion detected by GynocularTM. HPV positive women also had random punch biopsy from the cervix. The sensitivity, specificity and agreement between histology and gynocular diagnosis were estimated.rnrnResults: Total 6884 women were screened from April, 2014 to March, 2015. Total 684 women were examined by GynocularTM. A total of 28 cases of CIN2+ were detected. The sensitivity and specificity of Gynocular (IFCPC Grade-2 threshold) to detect CIN 2+ were 92.9% and 96.1% respectively. The exact agreement between Gynocular examination and histology to classify the cervical lesions was 55.5% with kappa value of 0.29 (95% C.I. 0.22–0.36) indicated ‘fair’ agreement. rnrnConclusion: There is a great need for an inexpensive colposcope to be used for programs in LMICs. The agreement of GynocularTM with histology was same as that of colposcopy reported in our earlier study conducted in the same setting. The logistic advantage of the device and ability to capture images using mobile phone are beneficial to use Gynocular TM for cervical cancer screening program. rn