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
- Gynecologic Oncology
Gynecologic Oncology treatment
Breast cancer
Session Introduction
Ingegerd Hellstrom
University of Washington, USA
Title: Detection of the HE4 protein in urine as a biomarker for ovarian neoplasms
Biography:
Dr. Hellstrom’s main area of interest is in ovarian cancer. Her most recent research activity is in the area of tumor diagnostics, they have identified two new biomarkers for the diagnosis of ovarian carcinoma by assaying serum and other body fluids. She is currently conducting a pilot study to provoke an immune response to ovarian cancer cells by “silencing†TGF-beta, a gene which can normally suppress the immune system
Abstract:
We have measured HE4 levels in urines and sera from normal donors, patients with ovarian neoplasms of low malignant potential (LMP) and ovarian cancer patients and correlated levels with clinical factors in ovarian cancer patients. Archived samples from controls, patients with LMP tumors and ovarian cancer were tested using commercial assays, as were serially collected serum and urine samples from women treated for stage III/IV serous ovarian cancer. Stage I/II and Stage III/IV serous ovarian cancer patients had HE4-positive urines similar to serum samples when tested at the same level of specificity (95%), while urine HE4 was more sensitive from patients with LMP tumors where 28% were HE4-positive versus 4% of sera (P=0.002). Mean levels of serum CA125 and HE4 decreased comparably in patients during initial treatment regardless of their primary platinum response, but mean urine HE4 levels decreased only 7% in primary platinum resistant patients while decreasing 68% in those who were sensitive. By 7 months after diagnosis, urine HE4 levels were higher in primary platinum resistant patients compared to those who proved to be sensitive (p=0.051) and persisted 12 months after diagnosis (p=0.014). HE4 values in urine also became positive in advance of clinical recurrence in several women while serum HE4 and serum CA-125 remained normal. We conclude that measuring HE4 in urine complements serum assays for the detection of ovarian cancer and propose that a “blinded†prospective study is performed on a much larger patient material and including women at increased risk for ovarian carcinoma
Liane Deligdisch
Mount Sinai Medical Center, USA
Title: Early Ovarian Carcinoma: Clinical-Pathological Correlations and Molecular Studies.
Biography:
Liane Deligdisch, MD is Professor of Pathology and Obstetrics-Gynecology and Reproductive Science, The Mount Sinai Medical Center and School of Medicine, New York, NY, USA. Nathan G. Kase, MD is Professor in Obstetrics-Gynecology and Reproductive Sciences, Professor of Endocrinology and Dean Emeritus, The Mount Sinai School of Medicine, New York, NY, USA. Carmel J. Cohen, MD is Professor of Obstetrics, Gynecology and Reproductive Science and Professor of Gynecologic Oncology, Ruttenberg Cancer Center, The Mount Sinai School of Medicine, New York, NY, USA. Research interest includes Anal Intraepithelial Lesions,Cervical Cancer,Cervical Intraepithelial Neoplasia,Cervicitis,Endometrial Cancer,Endometrial,Hyperplasia,Endometrial Intraepithelial Neoplasia,Endometriosis.
Abstract:
Ovarian carcinoma (OC) is the most lethal gynecological tumor, most cases being diagnosed in late stages due to paucity of symptoms and absence of specific tumor markers in early stages of the disease. Preinvasive (dysplastic) lesions have been described in the ovaries by histologic, morphometric and immunohistologic methods, and in the fallopian tubes. Five year survival of OC is 30-35% in all stages and 80-90% in the rarely diagnosed stage I when the tumor is confined to the ovary(ies). Review of 99 cases of Stage I OC revealed a shift in the histologic distribution of early OC which are mostly non-Serous OC (NSOC) vs. the predominance of Serous OC (SOC) in all stages. The predominant early OC are endometrioid, mucinous and clear cell carcinomas. The rare Stage I SOC are detected randomly, most due to intense follow-up of high-risk patients (BRCA1/2 positivity, personal or family breast cancer). The clinical background of the patients is different in the NSOC patients who are younger, often hyperestrogenic and infertile, with coexisting endometriosis, endometrial polyps/hyperplasia/neoplasia, symptomatic lesions leading to an earlier diagnosis than the mostly asymptomatic SOC. Stage I OC is a heterogeneous group of tumors requiring different therapeutic approaches. Our recent molecular studies including markers, some of which targeting stem cells (HLA, Notch 3, Betacatenin, GLI-2, Cyclin E) offer an insight into early carcinogenesis of OC and may have an impact on therapeutic choices of this elusive and often deadly neoplasm.
Gwyn Richardson
University of Texas Medical Branch, USA
Title: Bilateral salpingectomy: An opportunity for cancer prevention
Biography:
Gwyn Richardson is an Assistant Professor of Gynecologic Oncology at the University of Texas Medical Branch in Galveston TX. She is also the Associate Clerkship Director for the Obstetrics and Gynecology 3rd year Medical School Clerkship. She holds the Francis Eastland Conally Professorship in Gynecologic Oncology
Abstract:
Objective: Among cancer patients, thromboembolic events are a common and potentially fatal complication. This study was designed to determine the incidence of thromboembolic events in relation to the diagnosis, treatment and progression of disease in cervical cancer patients. Study Design: We reviewed records for cervical cancer patients treated at a single institution from 1995-2008. Data collected included demographic characteristics, stage, histologic type, treatment received, time to recurrence, salvage therapy, thromboembolic event and its temporal relationship to cancer diagnosis, and survival. Results: Seven hundred sixty-six patients were diagnosed with invasive cervical cancer during study period. Records were available on 747 patients for mean follow up of 33 months. The incidence of thromboembolic events in cervical cancer patients was 9.0%. Incidence of thromboembolic events was higher in patients with advanced stage. There was no statistically significant difference when accounted by race, smoking history or tumor histology. As expected in patient with advanced stage, treatment modality was related to increased incidence of thromboembolic events. Survival analysis data showed that patients with thromboembolic events had a significantly poorer survival than patients without thromboembolic events. Conclusions: Thromboembolic events at the time of cervical cancer diagnosis are associated with advanced disease and poor prognosis. Following therapy, thromboembolic events may be the first sign of recurrence and confers a grim prognosis.
Magdalena Klink
Polish Academy of Sciences, Poland
Title: Anti-ovarian cancer cells activity of nitric oxide donors
Biography:
Magdalena Klink has completed her PhD in 1994 and habilitation in 2005, at the University of Lodz. Since 2004 she has been working at the Institute of Medical Biology, Polish Academy of Sciences in Lodz, now an associate professor. She was the manager of several research projects funded by national organizations and the contractor of project from the European Regional Development Fund (POIG). She is supervisor in two finished doctoral. She is the author of 48 scientific publications and editor of a monograph. For several years, she serves as editor of the Mediators of Inflammation. In WSZKiPZ lectures in biology with genetics
Abstract:
Despite a significant improvement in the conventional anti-ovarian cancer therapies, tumor cell resistance to various cytostatic drugs remains a relevant problem. The Nitric Oxide (NO) donors - synthetic compounds that release NO, in vivo and/or in vitro, have been considered as a potential anti-cancer agent. The effect of NO donors on the biological activity of ovarian cancer cells in the presence or absence of cisplatin was determined. Two members of NONOates family with different half-live time were used. Various ovarian cancer cell lines as well as cancer cells isolated from ascites of patients with advanced stage of diseases were used in these studies. We found that NO donors inhibited the ovarian cancer cells growth mainly by induction their apoptosis. Moreover, NO donors decreased the activity of signaling proteins (STAT3 and AKT) involved in uncontrolled proliferation of ovarian cancer cells. We also found that NO donors have low ability to inhibit the production and secretion of pro-metastatic factors. Our study showed that NO donors significantly enhanced the susceptibility of ovarian cancer cells to cytotoxicity of cisplatin. We demonstrated that NO donors increased the number of late apoptotic ecrotic ovarian cancer cells treated with cisplatin. We also found that none of NO donors or their combination with cisplatin affects the expression of genes (ABCB1, BIRC5 and PTEN) involved in the drug resistance. The obtained results show that NO donors have a high potential of being a supporting compounds in the ovarian cancer therapies
Biography:
Adrian Senderowicz has served as Senior Vice President and Chief Medical Officer since September 2015. Dr. Senderowicz was most recently Chief Medical Officer and Senior Vice President, Clinical Development and Regulatory Affairs at Ignyta, Inc. Previously, he was Vice President, Global Regulatory Oncology at Sanofi, Chief Medical Officer at Tokai Pharmaceuticals, and Senior Medical Director, Oncology Clinical Development at AstraZeneca. Before his tenure at AstraZeneca, Dr. Senderowicz held a variety of leadership positions at the U.S. Food and Drug Administration Division of Oncology Drug Products in the Center for Drug Evaluation and Research and a variety of clinical and research positions with the National Cancer Institute/National Institutes of Health (NCI), including Investigator and Chief, Molecular Therapeutics Unit. He currently serves as a director of Puma Biotechnology, Inc., a publicly traded biopharmaceutical company. He completed his Internal Medicine residency training at the Icahn School of Medicine at Mount Sinai, and a Clinical Oncology Fellowship at the NCI. Dr. Senderowicz holds an M.D. degree from the School of Medicine at the Universidad de Buenos Aires in Argentina.
Abstract:
Background: Cerulean Pharma, Inc. is developing CRLX101, an investigational NDC with a camptothecin payload. CRLX101 has been investigated in more than 350 patients to date. Regimens administered have included monotherapy and combination therapy with bevacizumab in patients with renal cell carcinoma (Keefe, ASCO 2015, abstract #4543) and platinum-refractory ovarian cancer (Krasner, ASCO 2014, abstract #5581). Based on preclinical and early clinical data suggesting synergy between taxanes and topoisomerase 1 inhibitors, we started a Phase 1b trial for this combination in patients with platinum-resistant ovarian cancer. Methods: Cohorts of 3 patients were accrued in this trial. Two dose levels were planned as dose level 1: CRLX101 12 mg/m2 (every other week) in combination with paclitaxel 80 mg/m2 (weekly, 3 weeks on/1 week off); and dose level 2: CRLX101 15 mg/m2 (every other week) in combination with the same regimen of paclitaxel 80 mg/m2. The primary objective was to determine the maximum tolerated dose (MTD) administered in combination with weekly paclitaxel. Secondary objectives included pharmacokinetics, overall safety, tolerability, and initial signs of clinical activity of CRLX101 with weekly paclitaxel. Results: As of March 11, 2016, a total of 9 patients have been enrolled and treated at dose levels one (n=3) and two (n=6) and all 9 patients are evaluable for safety and response. Median age is 61 years (range, 49–73); median number of previous regimens was 3 (range, 1–4); GOG score performance status was 0 (6 patients) or 1 (3 patients). No dose-limiting toxicities have been reported at either dose level, thus the RP2D for this schedule is CRLX101 15 mg/m2 (every other week) and paclitaxel 80 mg/m2 (3 weeks on/1 week off). Adverse events (AEs) suspected to be related to study treatment were fatigue (6 patients, 67%), neutrophil count decreased (4 patients, 44%), nausea (4 patients, 44%), vomiting, alopecia, headache, infusion-related reaction, and urinary tract infection (all seen in 2 patients, 22%), as well as dizziness, sinusitis, ALT increased, AST increased, constipation, cystitis noninfective, dyspnea, anemia, and peripheral sensory neuropathy (all seen in 1patient, 11%). The only grade ≥3 treatment-related AE was neutropenia, which occurred in 2 patients (one grade 3 and one grade 4). Partial response and stable disease rates were 56% (5/9), and 11% (1/9), respectively. Moreover, CA125 responses (≥50% decline from baseline) were demonstrated in 33% of patients (3/9). As of March 11, 2016, 2 patients (at 15 mg/m2) are still receiving therapy. Conclusions: CRLX101 given every other week in combination with weekly paclitaxel (3 weeks on/1 week off) has demonstrated early signs of antitumor activity and has been generally welltolerated to date in patients with platinum-resistant ovarian cancer.
Klesia Pirola Madeira
Federal University of Espirito Santo, Brazil
Title: Breast cancer: Estrogen receptor SNPs as risk markers and hormone receptors expression as therapeutic drivers
Biography:
Klesia Pirola Madeira obtained her Doctoral degree in Biotechnology from the Federal University of Espirito Santo (UFES) in 2013. She is currently a Professor in the Department of Pharmacy and Nutrition at UFES. Her research focuses on using in vitro systems to identify novel compounds that effectively target the PI3K. Her findings will be important in designing more efficacious therapeutics against various cancers that rely on this pathway for their survival.
Abstract:
Breast cancer (BC) is the second leading cause of cancer-related death in US women. The ability to effectively treat patients can be complicated by risk factors including single nucleotide polymorphisms (SNPs) in the estrogen receptor gene (ESR1) and misdiagnosis of hormone receptors expression levels. Recently, single nucleotide polymorphisms in PvuII and XbaI have been discovered in the ESR1 gene. To study the significance of these changes, we analyzed the allelic frequenices of these SNPs in samples isolated from patients with BC. We found higher P and X alleles frequencies in Erα-positive BC. Furthermore, the pp and xx genotypes were found exclusively in patients with HT-TMX responsive BC. Analysis of the expression levels of the ER status in 61 BC cases using SP1 and 1D5 monoclonal antibodies revealed a high concoradance rate (96.7%) betwen both antibodies based on immunohistochemical analysis applying the Allred score. Similar analysis of the PgR status in 53 BC cases revealed that the monoclonal antibodies PgR636 and SP42 were suitable for diagnositic purposes while monoclonal the antibody ab62621 should be excluded due a lack of specifity. Taken together, we have revealed that the P allele is a novel biomaker for BC, confirmed that both the pp and xx genotypes enhance responsiveness to chemotherapy, and identified monoclonal antibodies that improve the accuracy of detecting ER and PgR status in BC patients.
Jan Blaakaer
Aarhus University Hopital, Denmark
Title: Is it possible to define an optimal time for chemotherapy after surgery for ovarian cancer?
Biography:
Professor, M.D., DMSc., Department of Gynaecology, Aarhus University Hospital. I graduated, as a medical doctor from Odense University in 1982 and became a specialist in gynecology and obstetrics in 1991. I became a Doctor of Medical Science (DMSc) in 1998 with a thesis submitted to Copenhagen University on ovarian cancer. All in all, I am the author of 135 peer-reviewed publications dealing with topics in gynecology and obstetrics. Moreover, I have written more than 80 publications in textbooks, booklets and newspapers. For a period of five years, I was a member of the European Board and College of Obstetrics and Gynecology (EBCOG), 1996-2000. I was Vice-president as well as President of the Danish Society of Obstetrics and Gynecology (DSOG), and for several years a member of the executive committee of the Nordic Society of Obstetrics and Gynecology (NFOG). At the moment I am member of the executive board of the Nordic Society of Gynecological Oncology (NSGO). My research is primarily concentrated on ovarian cancer and HPV related cancers, especially cervical and vulvar cancer. At the moment I am supervisor for 18 Ph.D. students and four research years students.
Abstract:
Objective: To investigate the actual time from primary surgery for ovarian cancer (OC) to initiation of chemotherapy (TI) amongst Danish women in 2005-2006, and to compare the survival for groups with early initiation (≤ median TI) and late initiation of adjuvant chemotherapy (>median TI). Methods: All Danish women who underwent surgery for OC in the period between 1 January 2005 to 31 December 2006 recorded in the Danish Gynaecological Cancer Database (DGCD) were included. The five-year survival was estimated overall and by TI exposure. The Cox proportional hazard regression analysis was used to compute the adjusted hazard ratio (HR). Results: The median TI was 32 days (25-75% quartile: 24 days; 41 days). The strongest prognostic factors for death were residual tumour and the International Federation of Obstetrics and Gynecology (FIGO) stage. The unadjusted HR for death in patients with TI > 32 days compared with TI ≤ 32 days was 0.85 (95% CI: 0.70; 1.04), p-value 0.12. When adjusted for residual tumour and FIGO-stage the HR was 1.13 (95% CI: 0.92; 1.39), p-value 0.26. The overall five-year survival was 42.8%, (95% CI: 38.9%; 46.5%). Conclusions: This nationwide population-based cohort study revealed a non-significant increased risk of death for patients with TI>32 days compared with the reference TI≤32 days. The strongest prognostic factors were residual tumour after surgery and FIGO-stage. The overall five-year survival was 42.8% (95% CI: 38.9%; 46.5%).
Liselotte Mettler
University Hospitals Schleswig-Holstein Campus Kiel ,Germany
Title: Surgical and medical therapy of endometriosis with hormonal and non-hormonal targets
Biography:
Liselotte Mettler was Deputy Director of the Department of Obstetrics and Gynecology, University Hospitals Schleswig-Holstein and from 2002-2008 also Head of the Gynecological Endocrinology and Reproductive Medicine Division at the same department. She is executive Director of the International Academy of Human Reproduction (IAHR) and believes in the goals and activities of this Scientific and Clinical Academy. She is president of the 16th World Congress of Human Reproduction in March 2015 in Berlin, Germany,Her research interast are in Reproductive Medicine, Gynecologic Endoscopic Surgery, Endometriosis, Ocarian tumours, hysterectomies
Abstract:
Study question: To evaluate 3 therapy strategies - Hormone therapy, surgery, and combined treatment for genital endometriosis in a university based teaching hospital. Summary answer: In the quest to find the most effective treatment of genital endometriosis, this clinical randomized study shows the lowest incidence of recurrence with combined surgical and medical treatment and improved pregnancy rate in any medically treated patients with or without surgery with the highest cure rate in the combined treatment group. What is already known? Endometriosis is a systemic disease, which needs various treatments as up to date no single treatment is successful in every patient. Study design, size and duration: Four hundred fifty patients with genital endometriosis, stages I-III, aged 18 to 44 years, before first laparoscopy: Patients were randomly assigned to 1 of 3 treatment groups, hormone therapy, surgery, or combined treatment. Patients were reevaluated at second-look laparoscopy, at 2 to 2 months after 3-month hormone therapy in groups 1 and 3 and at 5 to 6 months in group 2 (surgical treatment alone). Outcome data were focused on the endometriosis stage, recurrence of symptoms, and pregnancy rate. Main results and role of chance: All treatment options, independent of the initial Endoscopic Endometriosis Classification stage, achieved an overall cure rate of R50%. A cure rate of 60% was achieved with the combined treatment, 55% with exclusively hormone therapy, and 50% with exclusively surgical treatment. Recurrence of symptoms was lowest in patients who received combined treatment. Significant benefit was achieved for dysmenorrhea and dyspareunia. An overall pregnancy rate of 55% to 65% was achieved, with no significant difference between the therapeutic options. Limitations and reasons for caution: Although a good number of patients were included into this RCT, no clear picture of an optimal therapy could be obtained. In this still complex and poorly understood disease therefore all know therapy concepts should be used for the treatment of patients. Wider implications of the findings: After an initial diagnostic laparoscopy, be careful with repetitive laparoscopic surgeries.
Ines Vasconcelos
Charité Medical University of Berlin, Germany
Title: Is there a role for chemotherapy in the treatment of invasive borderline ovarian tumors?
Biography:
Dr. Ines Vasconcelos has completed her medical degree with honors at the University of Coimbra in Portugal and her doctoral studies with Magna Cum Laude at the Charité Medical University in Germany. She has published in several international peer-reviewed high-impact journals and serves as a member of the editorial board of the journal Advances in Modern Oncology Research (AMOR). She is currently working at the Berlin Oncological Center Kurfürstendamm
Abstract:
Borderline ovarian tumors (BOTs) were first described by Taylor in 1929 and have been a challenge for both pathologists and oncologists. BOT is a disease of younger, fertile women, generally with a benign course; however, a minority of patients progress and eventually succumb to the disease. Although the corrected survival for patients with disease confined to the ovary is 100% at 15 years, 30% of patients with serous BOT with invasive implants will develop persistent or recurrent tumor, most commonly low-grade ovarian serous carcinoma. For the group of patients with invasive implants, there is no consensus regarding standard therapy. At present, chemotherapy is offered mostly to patients with invasive implants, regardless of histological subtype. However, response to these agents remains suboptimal with recurrence estimates for patients for patients with BOT with invasive implants undergoing adjuvant treatment remaining high at 44.0%. In this presentation we will discuss the current evidence, or lack of thereof, to support the use of adjuvant treatment in patients with invasive implants in the primary treatment setting.
Morva Tahmasbi Rad
Goethe University, Germany
Title: Learning curve for laparoscopic staging of early and locally advanced cervical and endometrial cancer
Biography:
Morva Tahmasbi Rad is Specialist in Obstetrics and Gynecology at Goethe University, Germany. She is extending his valuable service as a Specialist and has been a recipient of many award and grants. Her research experience includes various programs, contributions and participation in different countries for diverse fields of study. Her research interests as a Specialist reflect in her wide range of publications in various national and international journals.
Abstract:
Background: Laparoscopic staging is rapidly evolving as an important surgical approach in the field of gynecology oncology. However, the specific learning curve associated with this approach remains poorly investigated. This study aimed to evaluate the learning curve for laparoscopic staging of uterine cancers. Methods: A series of 28 consecutive laparoscopic hysterectomies with or without pelvic and/or para-aortic lymph node sampling for the treatment of early and locally advanced endometrial or cervical cancer were performed between July 2008 and January 2011. The analyses of the learning curves of the institution were performed for 20 patients who had undergone pelvic lymphadenectomy and/ or para-aortal lymph node sampling. The learning curve period has also been compared with the last 26 patients who received laparotomy staging (“open†group) due to the same diagnosis and by the same surgical team. To assess the short and long-term outcomes, we used validated questionnaires to record the clinical and follow-up results, any complaints or subjective reports from the patients, and details of their quality of life. All data were collected prospectively in a database and reviewed retrospectively. The learning was evaluated using the cumulative sum (CUSUM) method. Results: The CUSUM learning curve consisted of two distinct phases: phase 1 (the initial 9 cases) and phase 2 (the subsequent cases) which presented the mastery phase, with the operative time of 397.7±63.5 versus 300.6±19.4 min (p>0.0001). The significance of the difference between the two phases and “open†group changed in terms of number of lymph nodes retrieved, intra-operative blood loss and hospital stay. The conversion rate of phase 1 was higher than phase 2 [2 (22.2%) and 1 (9%), respectively]. Conclusion: This series confirms previous study findings concerning the feasibility and the safety of laparoscopic staging and provides information for surgeons in single centers considering adopting an endoscopic strategy to monitor the different aspects of outcomes during the implementation process for internal benchmarking. The operative outcome of laparoscopic staging intervention improves with experience. The data reported in this article suggest that after a learning curve of 9 patients, a relevant improvement at least regarding the duration of the operation can be achieved for experienced surgeons who start performing laparoscopic staging of uterine cancers. However, due to the limited number of patients as well as number of para-aortic lymph node sampling procedures, further studies are required for firm conclusions to be drawn.
Hossam El Sokkary
Alexandria university, Egypt
Title: Role of pelvic lymphadenectomy in stage 1A endometrial carcinoma diagnosed preoperatively by pelvic ultrasonography and CT scan
Biography:
Hossam Hassan Aly Hassan El Sokkary is Lecturer of Obstetrics and Gynecology, Alexandria University, Alexandria, Egypt. He was Obstetrics and Gynaecology Residents at El Shatby Alexandria University Hospital, Alexandria, Egypt from 20 October 1996 to 19 October 1999. He was Assistant Lecturer from 4 January 2004 to 22 September 2008
Abstract:
Introduction: Endometrial cancer is the commonest gynecological cancer mostly affecting women in the postmenopausal age group. There is a debate regarding the need of pelvic lymphadenectomy in managing stage 1A diagnosed preoperatively, we try to evaluate this need. Objective: To evaluate the role of pelvic lymphadenectomy in stage 1A endometrial carcinoma diagnosed preoperatively by pelvic ultrasonography and CT scan as microscopic invasion of pelvic lymph nodes will not be seen by this imaging technique. Methods: 60 cases of endometrial carcinoma diagnosed by fractional curettage and proved to be stage 1A preoperatively by clinical examination, vaginal US and CT scan (negative myometrial invasion, ascites, LN spread and local spread) underwent total abdominal hysterectomy with salpingo-oopherectomy, peritoneal wash for cytology, omentectomy and pelvic lymphadenectomy (external iliac and obturator groups) after written informed consent. Histopathology of the uterus, tubes, ovaries, omentum and cytology of peritoneal wash were done for surgical staging, in addition histopathology of pelvic LN was done. Results: Histopathology of the cases revealed the following: 52 cases were endometrioid adenocarcinoma distributed as follows: 10 patients were grade 1, 35 patients were grade 2 and 7 patients were grade 3. Eight cases were serous papillary adenocarcinoma, 3 of them were grade 1 and 5 cases were grade 2. As regards myometrial invasion 9 cases of endometrioid carcinoma show invasion, 1 of grade 1, 3 of grade 2 and 5 of grade 3 in comparison to 4 cases of papillary serous adenocarcinoma 1 of grade 1 and 3 of grade 2, so 13 cases have been proved by histopathology to have myometrial invasion. As regards histopathology of pelvic LN 12 cases out of 60 have been proved to have metastatic lesion. Conclusion: There is no need for lymphadenectomy in stage 1A diagnosed preoperatively using CT scan and vaginal US, preventing high risk surgical intervention in this early stage
Xueqing Wang
Beijing Jishuitan Hospital, China
Title: Cell-cycle synchronization reverses Taxol resistance of human ovarian cancer cell lines
Biography:
Xueqing Wang worked in the Department of Obstetrics and Gynecology of Beijing Jishuitan Hospital as a Doctor and graduated from Peking Union Medical College Hospital with Doctoral degree in 2008. She has published many papers in reputed journals.
Abstract:
Taxol inhibits cell replication by disrupting normal mitotic spindle formation and arresting cell growth in the M phase of the cell cycle. Passage through mitosis is an absolute requirement for Taxol-induced death. The replication time of some ovarian cancer cells is approximately 27 h and resistant cell lines even more longer. Results from our laboratory indicates that most cells were in G0/G1 or S stage during the whole cells cycle and the resistant cell lines have a significantly higher proportion of cells existing in the G0-G1 stage of the cell cycle compared to the sensitive cell lines. Thus, a disparity exists between the longer doubling time of cancer cells (27 h) and the shorter window of Taxol action (3 h-9 h), as such most cells do not occupy the M stage during the short window of Taxol action. We speculated that formation of drug resistance toward Taxol in ovarian cancer could be partly attributed to the longer doubling time of these cells. We used cell-cycle synchronization to test the above assumption. Cell-cycle synchronization resulted in an increase in the number of cells passing through the M stage at a given time and reduced the toxicity of Taxol toward cells in the non-proliferative phase, improving its effectiveness and decreasing the chance of drug-resistant formation.
Bishoy Y A El-Aarag
Menofia University, Egypt
Title: Novel phthalimide analogs as anti-angiogenic and anti-cancer agents
Biography:
Bishoy El-Aarag has awarded PhD degree in the field of medical Biochemistry (Cancer Science and Therapy) through a scientific channel between Egypt (Menoufia University) and Japan (Okayama University). He works as a lecturer of Biochemistry at Faculty of Science, Menoufia University, Egypt
Abstract:
Phthalimide moiety is one of thalidomide metabolites and might be the effective part of thalidomide toward many diseases. The mode of action of thalidomide in cancer therapy mainly depends on its immunomodulatory and anti-angiogenic activity, therefore, the current study focused on the efficacy of the newly synthesized phthalimide derivatives as immunostimulatory/immunosuppressive agents against immune cells, and their growth inhibitory effect against various cancer cell lines, as well as their anti-angiogenic activity. A facile synthetic approach of novel phthalimide dithiocarbamate and dithioate analogs 4a-k, 5a-e and 5g-k was achieved by the reaction of N-chloromethyl or N-bromoethylphthalimide with carbon disulfide (CS2) and different amines. Phthalimide derivatives 5e and 5i exhibited the highest cytotoxic activities against MCF-7 and Hep-G2 cells. Both derivatives 5e and 5i inhibited nitric oxide (NO), tumor necrosis factor-α (TNF-α), vessel endothelial growth factor (VEGF) and its receptor (VEGFR). Derivative 5e showed immunosuppressive activity through its inhibition of immune cell functions and proliferation. Taken together, our study improved that some of the newly synthesized phthalimide derivatives may act as anti-angiogenic and anti-cancer agents
Kannan Vaidyanathan
Pushpagiri Institute of Medical Science & Research Center, India
Title: Mutation pattern in BRCA1/2 genes in Indian hereditary breast/ovarian cancers
Biography:
Kannan Vaidyanathan, MBBS, MD (Biochemistry) did Post-doctoral fellowship from Indian Institute of Science, Bangalore, India. He is Professor & Head, Department of Biochemistry and Deputy Medical Superintendent, Pushpagiri Medical College Hospital, Tiruvalla, Kerala. He has 75 publications, 25 indexed in PubMed, 3 textbooks and 2 textbook chapters. His textbook on Biochemistry sells ~25000 copies worldwide every year and has been translated to other languages, including Slovakian and Spanish. Awards won by him include APFCB (Asia Pacific Federation of Clinical Biochemists) Silver Jubilee scholarship (2007) and KP Sinha – PS Krishnan award for best original research article in Indian Journal of Clinical Biochemistry (2011).
Abstract:
Hereditary breast/ovarian cancers are responsible for 5-10% of breast cancers and 7-10% of ovarian cancers. Breast cancer is one of the most common cancers in Indian women. Women carrying BRCA1 or BRCA2 mutations have a lifetime risk of between 60% and 85% for development of breast cancer, and 26% and 54% for development of ovarian cancer for BRCA1, and between 10% and 23% for BRCA2. In this study, 61 breast and/or ovarian cancer patients with a positive family history of breast and/or ovarian cancer were screened for BRCA1/2 mutations. For mutation screening, conformation sensitive gel electrophoresis was used, followed by DNA sequencing, were heteroduplexes were detected. In the BRCA1 gene, 15 mutations were identified; (mutation frequency, 24.6%) and in the BRCA2 gene, two mutations were detected (mutation frequency, 3.28%). Of the BRCA1 mutations identified, 3 were novel mutations and 3 more were previously reported mutations. The mutation, 185delAG was found in 10 patients at a very high frequency of 16.4%. This mutation is detected in high proportion in Ashkenazi Jewish population (18% in breast/ovarian cancers and 1% in general population). A large number of polymorphisms were also detected in BRCA2 gene, which were normal population variants. The mutation spectrum of BRCA1/2 in other Indian studies also indicate a higher incidence of 185delAG mutation, and the important studies shall be reviewed. Haplotype analysis was carried out, and it was found to be different from Ashkenazi Jewish population. The possibility of founder mutation status need to be considered for BRCA1 185delAG mutation.
Somashekhar S P
Manipal Hospital, India
Title: Hyperthermic Intraperitoneal Chemotherapy in Ovarian Carcinoma
Biography:
Somashekhar.S.P,MS,MCh(Onco),FRCS.Edinburgh,Chairman & HOD Surgical Oncology,Manipal Health Enterprise,Graduation year 1994, MS and MCh oncosurgery 2000 year,FRCS. Edinburgh Editor in chief Indian Journal of Gynec oncology Treasurer Association of Gynecological Oncology India Consultant Surgical & Gynec. Onco & Robotic Surgeon,,Manipal Comprehensive Cancer Center,India ,Had several national and intrenstio skPublication and has authored several text Books in gynec oncology
Abstract:
Background: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS+ HIPEC) has been proposed as treatment for recurrent epithelial ovarian carcinoma. We evaluated the outcomes of CRS+HIPEC in recurrent epithelial ovarian cancers, in Indian patients. Methods: In this prospective non-randomized study between February 2013 & January 2015, 26 patients with advanced recurrent EOC, with no extra-abdominal disease treated with secondary CRS+HIPEC in a tertiary care cancer institution, Southern India, were analyzed. Belmonte® hyperthermia (HIPEC) pump with cisplatin 100 mg/m2, 41.5-43â°C for 90 minutes, in platinum sensitive cases & doxorubicin 15 mgs/m2+cisplatin 75 mgs/m2 in platinum resistant cases was used. Results: Among twenty six patients 18 were upfront & 8 were post chemotherapy. Median peritoneal carcinomatosis Index was 9.5 (Range 3-19). The extent of cytoreduction associated with longer hospital stay (p<0.001), delayed gastrointestinal recovery (p=0.039), infections (p=0.036), and ARDS (p=0.041). Completeness of cytoreduction score CC0 achieved in 24 and CC1 in 2 patients. Bowel resection required in 34.6%. Diaphragm stripping was required in 30.7% with resection in 7.6%. Median hospital stay was 12 days (range: 10-42 days). No 30 days mortality. Bowel fistula happened in 7.6% cases requiring re-exploration, temporary stomas, and wound related complications in 26%. At median follow-up of eighteen months, 11.5% recurrences (both platinum resistant cases recurred in peritoneal cavity and one patient also in liver parenchyma) and one platinum sensitive patient recurred isolated in peritoneal cavity. One death observed at 5th month of follow up due to pulmonary embolism. Conclusions: In our Indian study, secondary CRS+HIPEC is shown to be very promising in recurrent epithelial ovarian cancers patients with no extra-abdominal disease & good performance status and can be done with acceptable morbidity, using dedicated HIPEC machine resulting in good peritoneal control of disease & DFS.
Hazan Ozyurt
Dr. Lutfi Kirdar Kartal Research and Educational Hospital, Turkey
Title: The effect of escitalopram on anastrozole plasma concentrations in breast cancer patients
Biography:
Hazan Ozyurt is specialist in Radiation Oncology and has a PhD degree in Pharmacology and Clinical Pharmacology. She has published papers about normal tissue effects of radiation, the clinical outcomes of rectal and cervical cancer after chemoradiotherapy in respect to genetic characteristics of tumors and GABAergic and nitrergic systems of brain
Abstract:
Introduction: Anastrozole, an aromatase inhibitor, catalyses the conversion of androstenedione to estrodiol in peripheral tissues in postmenopausal women through inhibition of the cytochromal P450 enzyme. Genetic variability of the metabolizing enzymes, CYP3A and UGT1A, along with BMI may affect the pharmacokinetics and pharmacodynamics of anastrozole. Although depressive mood disorder is commonly observed in breast cancer patients and escitalopram, selective serotonin transport inhibitor, is one of the used agent in the treatment, pharmacokinetic interaction through the CY3A4 that metabolizes both anastrozole and escitalopram has not been investigated before. Aim: In this study we aimed to provide data showing the effects of escitalopram on anastrozole levels in breast cancer patients that may results in toxicity or in inefficacy. Methods: Escitalopram prescribed19 female breast cancer patients on the treatment of anastrazole more than one month were included in the study. Plasma anastrozole and serum estradiol concentrations were measured before and one month after escitalopram use. Because there were inter individual variations between the last anastrozole dose and blood sampling, maximum plasma concentrations (Cmax) were back extrapolated by using the following pharmacokinetic formula LogC= LogCmax-k. t1/2. Results: The mean Cmax of anastrozole was 27±2.9 ng/mL in 19 patients. There was no significant difference in Cmaxanastrozole level in respect to previous treatments, BMI (29.9 ≤ vs 29.9>) and other drugs used currently. 12 of 19 patients completed one month escitalopram treatment and the mean Cmax of anastrazole increased from 25.2±3.1 ng/mL to 37.3±3.4 ng/mL after escitalopram (p<0.05). The median estradiol level of 19 patients were <10 pg/mLand no significant change was occurred after escitalopram administration. While the Cmaxof anastrozole increased significantly (p<0.01). After escitalopram in obese patients (BMI > 29.9), no significant change was observed in non-obese patients (BMI ≤ 29.9). Conclusion: Escitalopram increases anastrozole level and this effect is more prominent in obese than non-obese patients. Pharmacokinetic interaction through CYP 3A4 may be the responsible from these findings. The effect of BMI on this interaction may be explained by the redistribution of both drugs from adipose tissue.
Sandeep Singh
Gajra Raja Medical College, India
Title: Laser induced breakdown spectroscopy (LIBS) in cervical cancer screening: A proposed tool
Biography:
Dr Sandeep Singh has completed his MBBS from Gajra Raja Medical College, Gwalior affiliated to Jiwaji University, Gwalior, India from 2007-2013. He is presently associated with, Shitla sahai institute of medical science Gwalior, India. He has published 16 National and International research articles in various reputed journals and delivered paper presentations at various platforms. His core area of interest includes cervical cancer screening, generation of new screening tools and policy framing. He is actively associated with NGOs to provide health care to the underserved communities.
Abstract:
Objective: Cervical cancer, one of the few highly preventable cancers through successful screening, is the most common cause of death from cancer in women in the developing world. This brief hypothesis postulates a screening tool aimed to have a real time screening of cervical cancer using LIBS modality. Methods: Laser Induced Breakdown Spectroscopy (LIBS) is a spectrochemical method for determining the elemental composition of various samples present in any phase, by simultaneously vaporizing and exciting the sample and thus it improves the spectrochemical techniques by eliminating the requirement of sample pre-treatment. LIBS system focuses a high peak power laser pulse onto a targeted material to produce a laser spark or microplasma. Elemental line spectra is created, collected and analyzed by a fiber spectrophotometer since nano- to micro-grams of material are ablated in femto- to nano-seconds (depending on the laser pulse duration), the whole process can be considered as minimally destructive and real time. Results: The postulated hypothesis is aimed to use laser induced breakdown spectroscopy (LIBS) in the screening of cervical cancer as trace mineral elements act as biological signature in tissues like bones, teeth, hair, blood, etc., from the living phase and store information regarding habitat, nutrition, and other environmental conditions. Previous researches have shown significant differences in concentrations of trace elements between normal and cancerous tissue cells. Conclusion: The technique is exemplified by suggested use of LIBS in studying biological samples such as tissues, gall stones, biological aerosols and in vivo cancer detection.