Tuesday, December 01, 2015
Professor Gabrielle Belz, a laboratory head in the institute's Molecular Immunology division, said the study's findings show that the appendix deserves more credit than it has historically been given.
"Popular belief tells us the appendix is a liability," she said. "Its removal is one of the most common surgical procedures in Australia, with more than 70,000 operations each year. However, we may wish to rethink whether the appendix is so irrelevant for our health....
A phase II study of paclitaxel for the treatment of ovarian stromal tumors: An NRG oncology/gynecologic oncology group study.
OBJECTIVE:To estimate the probability of complete clinical response and toxicity of paclitaxel as second-line chemotherapy in measurable disease patients with malignant tumors of the ovarian stroma, and to evaluate the value of inhibin for predicting response.
METHODS:Thirty-one patients with histologically confirmed ovarian stromal tumor were enrolled from 2000 to 2013. Patients were required to have measurable recurrent disease, and to have received only one prior chemotherapy regimen. Paclitaxel 175mg/m2 was administered over a three hour infusion, cycling every 21days. Inhibin levels were drawn within two weeks of initiation of treatment.
RESULTS:Of 31 women enrolled, there was only one complete response (3.2%), and partial response in eight of 31 cases (25.8%). The pretreatment inhibin level for the single patient who had complete response was 88pg/mL. Median progression-free survival was 10.0months and overall survival was 73.6months. Myelosuppression was common with 12 of 31 patients (38.7%) suffering grade 3 or 4 neutropenia, leukopenia, or anemia.
CONCLUSION:There were too few complete responses to warrant continued evaluation of paclitaxel as a single agent treatment for women with recurrent malignant ovarian stromal tumors with measurable disease according to the primary objective of the study. Toxicity of the regimen was acceptable. Pretreatment inhibin is not a reliable tumor marker as it was not elevated in the majority of patients.
A phase I trial of pegylated liposomal doxorubicin (PLD), carboplatin, bevacizumab and veliparib in recurrent, platinum-sensitive ovarian....
A phase I trial of pegylated liposomal doxorubicin (PLD), carboplatin, bevacizumab and veliparib in recurrent, platinum-sensitive ovarian, primary peritoneal, and fallopian tube cancer: An NRG Oncology/Gynecologic Oncology Group study
OBJECTIVE:To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of veliparib combined with PLD and carboplatin (CD) in patients with recurrent, platinum-sensitive epithelial ovarian cancer. To determine the tolerability at the MTD combined with bevacizumab.
METHODS:Patients received PLD (30mg/m2, IV) and carboplatin (AUC 5, IV) on day 1 with veliparib on days 1-7 (intermittent) or days 1-28 (continuous). Standard 3+3 design was used in the dose escalation phase with DLTs based on the first cycle. Once the MTDs were determined, cohorts of 6 patients were enrolled to each regimen with bevacizumab (10mg/kg on days 1 and 15) to assess feasibility. DLTs were based on the first 4cycles of treatment in the bevacizumab cohorts.
RESULTS:In the dose-escalation phase, 27 patients were treated at 3 dose levels with DLTs noted in 6 patients including grade 4 thrombocytopenia (n=4), and prolonged neutropenia >7days (n=3). At the MTD of veliparib (80mg p.o. b.i.d. for both dosing arms), myelosuppression was the DLT. At MTD, 12 additional patients were treated with bevacizumab with 9 patients experiencing DLTs including grade 4 thrombocytopenia (n=4), prolonged neutropenia >7days (n=1), grade 3 hypertension (n=5), and grade 5 sepsis (n=1).
CONCLUSIONS:The MTD of veliparib combined with CD is 80mg p.o. b.i.d. in women with recurrent, platinum-sensitive ovarian cancer. With bevacizumab, DLTs were noted in 9 out of 12 patients. Lower doses of veliparib will need to be considered when given in combination with platinum-based therapies.
Cancer predisposition genes: molecular mechanisms and clinical impact on personalized cancer care: examples of Lynch and HBOC syndromes
.... As a result, hereditary cancers are characterized by 1) early onset of cancer, often younger than 50 years at diagnosis compared with an average age of 60 years in the general population, 2) frequent synchronous and metachronous cancers of the spectrum that reflect a multiple or successive somatic events, and 3) a familial history of cancers through generations in which the cancer types correspond to the syndrome's tumor spectrum.....
(Lynch Syndrome section) Cancer risk in mutation carriers varies largely with cancer syndromes and the involved predisposition genes. The lack of a correlation between genotype and phenotype and the variable penetrance (the expressivity of the mutant gene) render the risk estimation very challenging. Indeed, for patients with Lynch syndrome, carriers of the same mutation can have different clinical manifestations even within the same family, and histologically similar malignancies can be caused by a variety of mutations of any one of the MMR genes....
The physiopathology of HBOC is quite similar to Lynch syndrome.
Monday, November 30, 2015
Cross-sectional study on comorbidities and adverse events in patients with advanced and recurrent ovarian cancer in France
The purpose of this study was to evaluate the prevalence of comorbidities and adverse events (AEs), and determine the treatment patterns according to platinum-sensitivity status in patients with advanced (stage IIIB–IV) or recurrent epithelial ovarian cancer (EOC).
ResultsOf the 127 patients included, 92 (72.4%) had advanced EOC and 35 (27.6%) had recurrent EOC. A total of 73 comorbidities were reported in 44 patients (34.6%). Vascular (10.2%), metabolic (7.1%), respiratory (5.5%), and psychiatric disorders (5.5%) were the most common types of comorbidities reported. Prevalence of AEs was 74.8%, of which 12.6% were classified as serious. The most common AEs were anemia (16.5%), hematologic events (12.6%), taste change (11.8%), and headache (7.1%)......
In this cross-sectional study of advanced and metastatic ovarian cancer patients, approximately one-third of patients were diagnosed with comorbidities, and approximately three-quarters were diagnosed with AEs (12.6% with severe AEs).
To learn more about the resources available within EPIC, please see the About EPIC section.
EPICentre: The lifestyle and cancer blog
Acrylamide and glycidamide hemoglobin adducts and epithelial ovarian cancer: a nested case-control study in non-smoking postmenopausal women from the EPIC cohort
Acrylamide was classified as 'probably carcinogenic to humans (group 2A)' by the International Agency for Research on Cancer. Epithelial ovarian cancer (EOC) is the fourth cause of cancer mortality in women. Five epidemiological studies have evaluated the association between EOC risk and dietary acrylamide intake assessed using food frequency questionnaires, and one nested case-control study evaluated hemoglobin adducts of acrylamide (HbAA) and its metabolite glycidamide (HbGA) and EOC risk; the results of these studies were inconsistent.
A nested case-control study in non-smoking postmenopausal women (334 cases, 417 controls) was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Unconditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between HbAA, HbGA, HbAA+HbGA, and HbGA/HbAA and EOC and invasive serous EOC risk.
No overall associations were observed between biomarkers of acrylamide exposure analyzed in quintiles and EOC risk; however, positive associations were observed between some middle quintiles of HbGA and HbAA+HbGA. Elevated but non-statistically significant ORs for serous EOC were observed for HbGA and HbAA+HbGA (ORQ5vsQ1:1.91, 95%CI:0.96-3.81 and ORQ5vsQ1:1.90, 95%CI:0.94-3.83, respectively); however, no linear dose-response trends were observed.
This EPIC nested case-control study failed to observe a clear association between biomarkers of acrylamide exposure and the risk of EOC or invasive serous EOC.
It is unlikely that dietary acrylamide exposure increases ovarian cancer risk; however, additional studies with larger sample size should be performed to exclude any possible association with EOC risk.
Systematic Review of Monitoring Criteria to Interpret CA125 Increments during 1st Line Chemo/Folow-Up
Systematic Review of Monitoring Criteria to Interpret CA125 Increments during First-Line Chemotherapy and the Subsequent Follow-Up Period among Patients with Advanced Epithelial Ovarian Cancer - systematic-review-of-monitoring-criteria-to-interpret-ca125-increments-during-firstline-chemotherapy-and-the-subsequent-followup-period-among-patients-with-advanced-epithelial-ovarian-cancer-jcop-1000101.pdf
Consistent criteria for indicating disease progression with CA125 could not be defined due to differences in trial design and selection of patients. The most promising criteria should be re-evaluated under similar and standardized conditions. Computer simulation models and change point algorithms may aid in identifying CA125 assessment criteria to be further validated in prospective clinica
CDC Media Report
The journal supplement includes 12 articles on research, surveillance, education campaigns, and partnerships that improve the experiences of survivors, their families, friends, and caregivers.
Women’s Health Care Chartbook - open access
Organization of the Chartbook on Women’s Health Care
Part of a series related to the National Healthcare Quality and Disparities Report (QDR).
Overview of the QDR
Overview of women, one of the priority populations of the QDR
Summary of trends in health care quality and disparities for females
Tracking of access and quality measures for rural females:
Access to Health Care
Person- and Family-Centered Care
Communication and Care Coordination
Effective Treatment of Leading Causes of Morbidity and Mortality
Increased public awareness on cancer prevention has focused efforts on inherited cancer predispositions. Risk assessment and mitigation are integral components in this prevention strategy. Most inherited cancer syndromes cross multiple disciplines and require a collaborative approach to management. In the gynecologic cancer arena, hereditary breast and ovarian cancer (HBOC) and Lynch syndrome (LS) have garnered the most attention. Inherited disorders that are associated with both colorectal cancer and gynecologic malignancies include LS and less commonly, Peutz-Jeghers syndrome, Li-Fraumeni syndrome, and Cowden syndrome. Significantly, approximately half of women with LS will have an endometrial cancer as their sentinel malignancy with a median of 11 years prior to a colon cancer diagnosis (1). Therefore, an understanding of the associated cancers and recommended screening and management guidelines are critical to optimize patient care and ultimately outcomes. In this review, we will specifically focus on LS and its implications for the gynecologist......
.....LS-related ovarian cancer is diagnosed at a younger age than sporadic cases, and is more likely to be early stage. Endometrioid and clear cell histologies are more common in the Lynch cases. In a histopathologic study of cases with nonserous ovarian cancer, 21% were determined to have loss of mismatch repair on immunohistochemistry, and in their cohort of Lynch-associated ovarian cancers, there were no serous or mucinous cancers (11). There is very limited information regarding survival comparing the sporadic and familial cases, but it appears there are no significant differences (5,12). Synchronous primary endometrial cancer is found in approximately 22% of LS-associated ovarian cancer (5). Conversely, about 7% of patients with synchronous primary endometrial and ovarian cancer at time of diagnosis are found to have LS (13).....
Adding Dimensions to the Analysis of the Quality of Health Information of Websites Returned by Google: Cluster Analysis Identifies Patterns of Websites According to their Classification and the Type of Intervention Described | Digital Health
As more patients search for health information on the Internet, many studies have analyzed the quality of health information available on the web for different pathological conditions. There is a concern that, because the Internet is practically not controlled or regulated, this might expose the public to misinformation, particularly those with low information literacy, which is the ability to critically appraise the information (1, 2). This could potentially result in patients turning to non-approved therapies, whose efficacy (and risks associated) has not been scientifically proven. Furthermore, in recent years, there have been an increasing number of commercial websites selling counterfeit medicines, with additional risks for vulnerable patients (3).
Although there are a number of specialized health websites, most patients will use generic search engines, such as Google, to search for health-related information (4), and several studies have tried to address the quality of health information available on the Internet using various methods...............Performing a cluster analysis of websites, based on their classification and the intervention described, can identify patterns of websites pointing patients toward one or more treatments. In the specific example of health-related query studied here, we were surprised that commercial websites ranked low in the search list. In terms of the type of intervention recommended, complementary/alternative medicine occurred more often than approved, EBM-based drugs, but the latter were more frequent in the top 10 results, possibly due to the intrinsic higher IQ features of these websites......
As our population ages, there has been an increase in the prevalence of cancer and heart disease . Modern treatment strategies have led to improvement in the chances of surviving a diagnosis of cancer; however, these treatments can come at a cost . Cardiotoxicity, a relatively new term in the medical literature, refers to the impact of cancer therapies on the heart and cardiovascular system [3, 4]. Cohort studies in pediatric cancer survivors have shown that cardiotoxicity is the second leading cause (after cancer recurrence) of morbidity and mortality in cancer survivors . The potential negative impact of cancer drugs on the heart, however, is not new. In fact, we have known for years that cancer drugs, such as the anthracyclines, can cause severe and permanent heart damage including heart failure (HF). So why is there growing interest now?....
Immunohistochemical characterization of appendiceal mucinous neoplasms & value of SATB2 in their distinction from primary ovarian mucinous tumors
The distinction between primary ovarian mucinous tumors and appendiceal mucinous neoplasms metastatic to the ovary can be challenging given the overlap of morphologic features and immunohistochemical expression of traditional markers. SATB2 has been recently described as a sensitive and specific marker of colorectal epithelium. Its expression in appendiceal mucinous tumors and its role in their distinction from ovarian neoplasms have not been fully characterized.
Methods and results
Immunohistochemistry was performed in tissue microarrays from 32 primary appendiceal mucinous tumors (25 low grade appendiceal mucinous neoplasms and 7 adenocarcinomas) and 40 ovarian mucinous neoplasms (20 borderline tumors and 20 adenocarcinomas).
Risk factors for cancer occurrence and for cancer death
Cancers affecting the same organ are no longer considered as a single disease entity. The wisdom that risk factors for cancer occurrence would be the same as for the risk for aggressive cancer or of cancer death is not correct. For instance, reproductive factors have a strong influence on the risk of breast cancer but little influence on the risk of breast cancer death . Adiposity is associated with reduced breast cancer risk in premenopausal women. However, the risk of death from breast cancer in premenopausal women increases with adiposity . High fertility is associated with reduced risk of breast cancer. However, women giving birth in their 40s have become increasingly common, and breast cancer occurring in the first 2 years after childbirth is known to be more lethal . Another example is smoking in prostate cancer. If smoking is not a risk factor for prostate cancer occurrence, it seems to be associated with the occurrence of fatal prostate cancer .The search for hereditary, lifestyle, and environmental factors that would be involved in the occurrence of potentially life-threatening cancers has really started only after 2000, mainly because of the longstanding false impression that risk factors for cancer occurrence and for cancer death were similar.....
Our results are in line with several previous studies , , , , , , and in particular, our findings are concordant with two recent studies ,  showing that age is an independent predictor of non-administration of either surgery or chemotherapy.
Ovarian cancer is the fourth most common cancer among women in France, and mainly affects the elderly. The primary objective of this study was to compare treatment of ovarian cancer according to age.
Dr. Frederick Greene speaks with David P. Winchester about the current and future state of the National Cancer Database, sponsored by the American College of Surgeons.
Association of Coffee Consumption With Overall and Cause-Specific Mortality in a Large US Prospective Cohort Study
Concerns about high caffeine intake and coffee as a vehicle for added fat and sugar have raised questions about the net impact of coffee on health. Although inverse associations have been observed for overall mortality, data for cause-specific mortality are sparse. Additionally, few studies have considered exclusively decaffeinated coffee intake or use of coffee additives. Coffee intake was assessed at baseline by self-report in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Hazard ratios were estimated using Cox proportional hazards models. Among 90,317 US adults without cancer at study baseline (1998–2001) or history of cardiovascular disease at study enrollment (1993–2001), 8,718 deaths occurred during 805,644 person-years of follow-up from 1998 through 2009. Following adjustment for smoking and other potential confounders, coffee drinkers, as compared with nondrinkers, had lower hazard ratios for overall mortality (<1 cup/day: hazard ratio (HR) = 0.99 (95% confidence interval (CI): 0.92, 1.07); 1 cup/day: HR = 0.94 (95% CI: 0.87, 1.02); 2–3 cups/day: HR = 0.82 (95% CI: 0.77, 0.88); 4–5 cups/day: HR = 0.79 (95% CI: 0.72, 0.86); ≥6 cups/day: HR = 0.84 (95% CI: 0.75, 0.95)). Similar findings were observed for decaffeinated coffee and coffee additives. Inverse associations were observed for deaths from heart disease, chronic respiratory diseases, diabetes, pneumonia and influenza, and intentional self-harm, but not cancer. Coffee may reduce mortality risk by favorably affecting inflammation, lung function, insulin sensitivity, and depression.
Aurora Kinase Inhibitors in Oncology Clinical Trials: Current State of the Progress. - PubMed - NCBI
Sarah Cannon Research Institute at HealthONE, Denver, CO
Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX.
Center for Personalized Cancer Therapy, Moores Cancer Center, University of California San Diego, La Jolla, CA
The Aurora kinase family of kinases (Aurora A, B, and C) are involved in multiple mitotic events, and aberrant expression of these kinases is associated with tumorigenesis. Aurora A and Aurora B are validated anticancer targets, and the development of Aurora kinase inhibitors has progressed from preclinical to clinical studies. A variety of Aurora A, B and pan-Aurora kinase inhibitors have entered the clinic. The main side effects include febrile neutropenia, stomatitis, gastrointestinal toxicity, hypertension, and fatigue. Responses including complete remissions have been described in diverse, advanced malignancies, most notably ovarian cancer and acute myelogenous leukemia. This review highlights the biologic rationale for Aurora kinase as a target, and clinical trials involving Aurora kinase inhibitors, with particular emphasis on published early phase studies, and the observed anti-tumor activity of these agents.
The utility of web mining for epidemiological research: studying (obituaries) the association between parity and cancer risk
Background The World Wide Web has emerged as a powerful data source for epidemiological studies related to infectious disease surveillance. However, its potential for cancer-related epidemiological discoveries is largely unexplored.
Methods Using advanced web crawling and tailored information extraction procedures, the authors automatically collected and analyzed the text content of 79 394 online obituary articles published between 1998 and 2014. The collected data included 51 911 cancer (27 330 breast; 9470 lung; 6496 pancreatic; 6342 ovarian; 2273 colon) and 27 483 non-cancer cases. With the derived information, the authors replicated a case-control study design to investigate the association between parity (i.e., childbearing) and cancer risk. Age-adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for each cancer type and compared to those reported in large-scale epidemiological studies.
Results Parity was found to be associated with a significantly reduced risk of breast cancer (OR = 0.78, 95% CI, 0.75-0.82), pancreatic cancer (OR = 0.78, 95% CI, 0.72-0.83), colon cancer (OR = 0.67, 95% CI, 0.60-0.74), and ovarian cancer (OR = 0.58, 95% CI, 0.54-0.62). Marginal association was found for lung cancer risk (OR = 0.87, 95% CI, 0.81-0.92). The linear trend between increased parity and reduced cancer risk was dramatically more pronounced for breast and ovarian cancer than the other cancers included in the analysis.
Conclusion This large web-mining study on parity and cancer risk produced findings very similar to those reported with traditional observational studies. It may be used as a promising strategy to generate study hypotheses for guiding and prioritizing future epidemiological studies.
U.S. FDA Announces Glades Drugs' Nationwide Voluntary Recall Of Compounded Multivitamins Containing High Amounts Of Vitamin D3
ConsumersFaith Washington, Pharmacist
Firm Press Release
Consumption of this product may result in vitamin D toxicity, which may be severe and may lead to life-threatening outcomes if left untreated. Patients suffering adverse effects from high Vitamin D levels (Cholecalciferol) may not initially show symptoms. Therefore, patients who have received these compounded capsules should stop taking this medication and immediately seek medical attention.
Symptoms of short-term vitamin D toxicity are due to high calcium levels (also known as hypercalcemia) and include confusion, increased urination, increased thirst, loss of appetite, vomiting, and muscle weakness. Acute hypercalcemia may intensify tendencies for heart arrhythmias and seizures and may increase the effects of certain heart drugs. Long-term toxicity may cause kidney failure, increase in calcium deposits in the blood and soft tissue, bone demineralization and pain. Patients with conditions such as liver disease or chronic kidney failure may be at increased risk for developing vitamin D toxicity.....
Cochrane Review: Platelet transfusions are used to prevent bleeding in people with low platelet counts due to treatment-induced bone marrow failure
Comparison of different platelet count thresholds to guide administration of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation - The Cochrane Library
Findings from this review were based on three studies and 499 participants. Without further evidence, it is reasonable to continue with the current practice of administering prophylactic platelet transfusions using the standard trigger level (10 x 10
Plain language summary
Platelet transfusions are used to prevent bleeding in people with low platelet counts due to treatment-induced bone marrow failure
We evaluated the evidence about whether platelet transfusions given to prevent bleeding in people with lower platelet counts (for example 5 x 10
People with blood cancers may have low platelet counts due to their underlying cancer. Blood cancers may be treated with chemotherapy and stem cell transplantation, and these treatments can cause low platelet counts. Platelet transfusions may be given to prevent bleeding when the platelet count falls below a prespecified threshold platelet count (for example 10 x 10
The evidence is current to July 2015. We found no new studies in this update of the review. This review identified three randomised controlled trials that compared giving platelet transfusions to prevent bleeding when the platelet count is 10 x 10
Two of the three studies reported sources of funding. Neither of the studies that reported funding sources were industry sponsored.
Giving platelet transfusions to people with low platelet counts due to blood cancers or their treatment to prevent bleeding when the platelet count was 10 x 10
Giving platelet transfusions to prevent bleeding only when the platelet count was 10 x 10
None of the three studies reported any quality of life outcomes.
Findings from this review were based on three studies and 499 participants. Without further evidence, it is reasonable to continue using platelet transfusions to prevent bleeding based on the current standard transfusion threshold (10 x 10
Quality of the evidence
The evidence for most of the findings was of low quality. This was because participants and their doctors knew which study arm the participant had been allocated to, and also the estimate of the treatment effect was imprecise.
AUTHORS' CONCLUSIONS:Cannabis-based medications may be useful for treating refractory chemotherapy-induced nausea and vomiting. However, methodological limitations of the trials limit our conclusions and further research reflecting current chemotherapy regimens and newer anti-emetic drugs is likely to modify these conclusions.
Sunday, November 15, 2015
Biomarkers to Guide Immunotherapy Treatment of Solid Tumors: Strategies to Promote Best Practices for Quality Care
Source: Biomarkers to Guide Immunotherapy Treatment of Solid Tumors: Strategies to Promote Best Practices for Quality Care
Robert A. Anders, MD, PhD; Michael B. Atkins, MD; Naiyer Rizvi, MD; and Janis M. Taube, MD, MSc, discuss the evolving role of biomarkers to identify patients with cancer most likely to benefit from immune checkpoint inhibitors.
Upon completion of this activity, participants should be able to:
- Describe the role of the immune system in pathogenesis and cancer
- Explain the mechanism of action and targeted pathways of various classes of immunotherapies
- Describe the status of emerging biomarkers being evaluated in clinical trials that may affect immunotherapy treatment decisions in the near future
- Identify patients with cancer who are likely to benefit from treatment with immunotherapy
Topics covered include:
- The Immune System in Cancer
- The Immune Response to Cancer and Opportunities for Active Immunotherapy
- Immune Checkpoint Blockade
- PD-L1 as a Potential Biomarker for Immune Checkpoint Inhibitors
- The Status of PD-L1 Biomarker Testing in the Clinic
- Other Investigational Biomarkers for Immune Checkpoint Inhibitors
The goal of
this survey is to find out whether or not people with ovarian cancer and
their close relatives have been offered genetic counseling and/or
genetic testing. In order to do this, we are sending out this short
online survey through online support groups for ovarian cancer. We
aim to reach as many people as possible nationwide (or even worldwide)
with either a personal history of ovarian cancer, or those who have a
relative with ovarian cancer. We hope to better understand the
experiences of people with ovarian cancer or a family history of ovarian
cancer, regardless of whether or not they have been offered
or undergone genetic testing.
If you have ever been diagnosed with ovarian cancer, or if you have
a mother, sister, or daughter who has been diagnosed with ovarian
cancer, you are eligible to participate in our survey. You can be any
gender to take our survey, but you must be 18 years old or older.
is a voluntary 26 question survey, and it will take about 15-20 minutes
to complete. All answers are completely anonymous with no risks to the
participants. You may exit the survey at any time. Questions marked
with an asterisk (*) are required. Please only take this survey once.
study is being conducted as part of a Master’s thesis requirement by a
student in the Department of Genetic Counseling at the University of
Arkansas for Medical Sciences and has received Institutional Review
Board (IRB) approval: Protocol #204292.
If you have any questions about the survey, please email us at email@example.com
We greatly appreciate your responses!
This is a voluntary 26 question survey, and it will take about 15-20 minutes to complete. All answers are completely anonymous with no risks to the participants. You may exit the survey at any time. Questions marked with an asterisk (*) are required. Please only take this survey once.
This study is being conducted as part of a Master’s thesis requirement by a student in the Department of Genetic Counseling at the University of Arkansas for Medical Sciences and has received Institutional Review Board (IRB) approval: Protocol #204292.
If you have any questions about the survey, please email us at firstname.lastname@example.org
We greatly appreciate your responses!
Saturday, November 14, 2015
Aspirin in the 21st century—common mechanisms of disease and their modulation by aspirin: a report from the 2015 scientific conference of the international aspirin foundation, 28 August, London, UK. ecancermedicalscience - The open access journal from the European Institute of Oncology and the OCEI
Recommendations All patients who receive highly emetogenic chemotherapy regimens (including anthracycline plus cyclophosphamide) should be offered a three-drug combination of an NK1 receptor antagonist, a 5-HT3 receptor antagonist, and dexamethasone. The oral combination of netupitant and palonosetron plus dexamethasone is an additional treatment option in this setting. The remaining recommendations from the 2011 ASCO guideline are unchanged pending a full update. Additional information is available at www.asco.org/guidelines/antiemetics and www.asco.org/guidelineswiki.
Natural selection, inflammation may hold key to age-associated cancer risk: Without age-associated inflammation, older mice developed leukemia no faster than young mice
The incidence of cancer increases with age. Conventional wisdom blames this on age-dependent accumulation of cancer-causing mutations. A University of Colorado Cancer Center study published in the Journal of Clinical Investigation tells another story......
- Curtis J. Henry, Matias Casás-Selves, Jihye Kim, Vadym Zaberezhnyy, Leila Aghili, Ashley E. Daniel, Linda Jimenez, Tania Azam, Eoin N. McNamee, Eric T. Clambey, Jelena Klawitter, Natalie J. Serkova, Aik Choon Tan, Charles A. Dinarello, James DeGregori. Aging-associated inflammation promotes selection for adaptive oncogenic events in B cell progenitors. Journal of Clinical Investigation, 2015; DOI: 10.1172/JCI83024
We have earlier demonstrated that breast cancer and small-cell lung cancer express functional NMDA receptors that can be targeted to promote cancer cell death. Human ovarian cancer tissues and human ovarian cancer cell lines (SKOV3, A2008, and A2780) have now been shown to also express NMDA-receptor subunit 1 (GluN1) and subunit 2B (GluN2B). Seventeen ovarian cancers in two arrays were screened by immunohistochemistry using polyclonal antibodies that recognize an extracellular moiety on GluN1 and on GluN2B. These specimens comprised malignant tissue with pathology diagnoses of serous papillary cystadenocarcinoma, endometrioid adenocarcinoma, and clear-cell carcinoma. Additionally, archival tissues defined as ovarian adenocarcinoma from ten patients treated at this institute were also evaluated. All of the cancerous tissues demonstrated positive staining patterns with the NMDA-receptor antibodies, while no staining was found for tumor-adjacent normal tissues or sections of normal ovarian tissue. Human ovarian adenocarcinoma cell lines (A2008, A2780, SKOV3) were demonstrated to express GluN1 by Western blotting, but displayed different levels of expression. Through immunocytochemistry utilizing GluN1 antibodies and imaging using a confocal microscope, we were able to demonstrate that GluN1 protein is expressed on the surface of these cells. In addition to these findings, GluN2B protein was demonstrated to be expressed using polyclonal antibodies against this protein. Treatment of all ovarian cell lines with antibodies against GluN1 was found to result in decreased cell viability (P<0.001), with decreases to 10%-25% that of untreated cells. Treatment of control HEK293 cells with various dilutions of GluN1 antibodies had no effect on cell viability. The GluN1 antagonist MK-801 (dizocilpine maleate) and the GluN2B antagonist ifenprodil, like antibodies, dramatically decreased the viability of A2780 ovarian tumor cells (P<0.01). Treatment of A2780 tumor xenografts with ifenprodil (2.5 mg/kg body weight/day) significantly reduced tumor growth in nu/nu mice. Our findings suggest that both GluN1 and GluN2B proteins as membrane components could be readily available targets for the treatment of most ovarian cancers.
Pharmacodynamic markers and clinical results from the phase 2 study of the SMAC mimetic birinapant in women with relapsed platinum-resistant or -refractory epithelial ovarian cancer
BACKGROUND:Inhibitors of apoptosis proteins (IAPs) are key regulators of apoptosis and are frequently dysregulated in ovarian cancer. It was hypothesized that blocking IAPs with birinapant would increase tumor cell death and result in objective responses for women with platinum-refractory and -resistant ovarian cancer.
METHODS:In this phase 2, Cancer Therapy Evaluation Program-sponsored study, patients received birinapant at 47 mg/m2 on days 1, 8, and 15 of 28-day cycles. Pharmacokinetics were obtained during cycle 1. Plasma, peripheral blood mononuclear cells (PBMCs), and percutaneous tumor biopsy samples were collected before cycle 1 and after 6 weeks. The primary endpoint was an objective response or progression-free survival lasting greater than 6 months in a mini-max design.
RESULTS:Eleven patients received birinapant; after this, accrual was terminated for lack of a clinical benefit. Birinapant was well tolerated, with predominantly grade 2 adverse events and 1 case of grade 3 lymphopenia. Pretreatment biopsy samples and PBMCs were collected; paired posttreatment biopsy samples and PBMCs were collected from 7 and 10 patients, respectively.
Friday, November 13, 2015
Join us for the 19th Ovarian Cancer National Conference
National Cancer Institute
.....Based on the available evidence, Dr. Bergö said he was extremely concerned with the aggressive marketing of antioxidants to cancer patients. The data strongly suggest that using antioxidants “could be really dangerous in lung cancer and melanoma, and possibly other cancers,” he said. “And because there’s no strong evidence that antioxidants are beneficial, cancer patients should be encouraged to avoid supplements after they have a diagnosis.”
Health - CBC News
Five types of cancer were included in the report — lung, ovarian, pancreatic, liver and esophageal — for which the surgical route is often considered complex and high risk, although still the best chance for a cure or the management of the disease if it's caught in the earlier stages.
Thursday, November 12, 2015
Commentary: PD-L1 Expression as a Predictive Biomarker: Is Absence of Proof the Same as Proof of Absence?
JAMA Network - full text
.... Identifying the subset of patients who are most likely to respond to anti–PD-L1 therapy is the first step toward individualized therapy. As a biomarker, however, PD-L1 immunohistochemistry offers poor sensitivity and reproducibility, and as a result, these patients may be unfairly excluded from clinical trials. To offer this potentially life-saving personalized immune-based therapy to as many patients as possible, we need to develop a multifaceted predictive biomarker system that integrates checkpoint inhibitors such as PD-L1, tumor mutations, and inflammatory cells.
JAMA Network - full text
The codevelopment of effective, safe anti–PD-1/PD-L1 agents with companion diagnostic assays faces significant challenges that could impede advancement of this therapeutic class if not properly addressed. Harmonization of current PD-L1 assays would standardize testing, provide guidelines for optimal PD-L1 evaluation, and may potentially circumvent this looming problem.
OBJECTIVES:After a diagnosis of ovarian cancer, positive BRCA mutation status confers a transient mortality benefit that diminishes with time. The majority of women who survive for 10-12years are effectively cured of their disease. Thus, it is important to estimate the probability of long-term survival by BRCA mutation status and treatment-related factors.
METHODS:We included unselected epithelial ovarian cancers diagnosed in Ontario, Canada from 1995 to 1999 and from 2002 to 2004. Clinical information was obtained from medical records. Survival status was determined by linkage to the Ontario Cancer Registry. We estimated the annual mortality for these patients. We compared women who did and did not survive 10years for a range of factors including BRCA mutation status and extent of residual disease post-surgery.
Statement by the Kommission Ovar of the AGO: The New FIGO and WHO Classifications of Ovarian, Fallopian Tube and Primary Peritoneal Cancer
- The New FIGO Classification
- The New WHO Classification
Clear cell tumors
The new WHO classification has not resulted in any significant changes in the classification of clear cell tumors. Clear cell BOTs are very similar to clear cell adenomas and parts of both entities are usually present in tumors. In contrast, clear cell carcinomas are irregular, with papillary structures, solid parts with desmoplastic hyalinized stroma, and high-grade nuclear atypia . Clear cell carcinomas may be associated with Lynch syndrome but also with endometriosis and are the most common ovarian carcinoma with paraneoplastic symptoms (thromboembolism and hypercalcemia) , .
Wednesday, November 11, 2015
Medscape (print preview page)
|Decrease in sexual interest
|Difficulty losing weight
Thinning hair, skin, nails
Weight gain around middle
Glucose intolerance/insulin resistance
Suppressed immune system
Anxiety, anger, agitation
Hair loss/male-patterned hair growth
|Decline in muscle tone|
Decreased sex drive
Thin lips/saggy cheeks
Trouble reaching climax
BRCA1 and BRCA2 mutations in Japanese patients with ovarian, fallopian tube, and primary peritoneal cancer
The contribution of BRCA1 and BRCA2 to ovarian cancer in Japanese patients is still unclear. This study investigated the frequency of germline mutations in BRCA1/2 in Japanese patients with ovarian, peritoneal, or fallopian tube cancer, regardless of their family histories, which were suggestive of hereditary breast and ovarian cancer.
Ninety-five unselected women with ovarian cancer who were seen from 2013 to 2015 at Yamanashi Prefectural Central Hospital were enrolled. Analyses of BRCA1/2 gene mutations were performed with next-generation sequencing.
Twelve of the 95 patients (12.6%), including 5 in the BRCA1 (5.3%) and 7 in the BRCA2 (7.4%), had deleterious mutations. Among the 36 cases with a family history, 6 (16.7%) were found to carry mutations in BRCA1 and BRCA2. Notably, 6 of the 59 cases (10.2%) without a family history also had BRCA1/2 germline mutations. There was no statistical difference between the 2 groups (P = .36). The presence of mutations and their clinical relevance were studied. Mutation carriers were diagnosed at advanced stages (100% of positive cases among stage III or IV cases) and had poor prognostic histological subtypes (100% of positive cases had high-grade serous adenocarcinomas).
CONCLUSIONSIn this unselected Japanese population, approximately 13% of the cases with ovarian cancer appeared to be associated with an inherited risk, regardless of a family history. This finding indicates that BRCA1/2 genetic testing should be performed for all patients with ovarian cancers.
Surgical management of ovarian carcinoma metastatic to the breast and axilla: A role for metastasectomy?
As patients with ovarian cancer are living longer, surgeons will be faced with the management of metastatic lesions amenable to resection more frequently. We present two patients with ovarian cancer metastatic to the breast who underwent resection for their metastases, but their outcomes differed significantly. After reviewing the literature, we propose that there can be definite benefit to resection in the appropriately selected patients and discuss factors to consider prior to proceeding with surgery.
Inheritance of a germline mutation in one of the DNA mismatch repair (MMR) genes or the EPCAM gene is associated with an increased risk of colorectal cancer, endometrial cancer, and other adult malignancies (Lynch syndrome). The risk of childhood cancers in Lynch syndrome families, however, is not well studied. Using data from the Colon Cancer Family Registry, we compared the proportion of childhood cancers (diagnosed before 18 years of age) in the first-, second-, and third-degree relatives of 781 probands with a pathogenic mutation in one of the MMR genes; MLH1 (n = 275), MSH2 (n = 342), MSH6 (n = 99), or PMS2 (n = 55) or in EPCAM (n = 10) (Lynch syndrome families), with that of 5073 probands with MMR-deficient colorectal cancer (non-Lynch syndrome families). There was no evidence of a difference in the proportion of relatives with a childhood cancer between Lynch syndrome families (41/17,230; 0.24 %) and non-Lynch syndrome families (179/94,302; 0.19 %; p = 0.19). Incidence rate of all childhood cancers was estimated to be 147 (95 % CI 107–206) per million population per year in Lynch syndrome families and 115 (95 % CI 99.1–134) per million population per year in non-Lynch syndrome families. There was no evidence for a significant increase in the risk of all childhood cancers, hematologic cancers, brain and central nervous system cancers, Lynch syndrome-associated cancers, or other cancers in Lynch syndrome families compared with non-Lynch syndrome families. Larger studies, however, are required to more accurately define the risk of specific individual childhood cancers in Lynch syndrome families.