- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.
- A fifth of heavily pretreated patients with advanced cancers responded to a monoclonal antibody (MPDL3280A) that blocks a tumor's ability to hide from the immune system.
- Note that in another study, concurrent treatment with ipilimumab (Yervoy) and the PD-1 targeted drug nivolumab led to substantial tumor shrinkage in roughly half of patients with difficult to treat, advanced melanoma.
Saturday, May 18, 2013
Concordance Between the Findings of Epidemiological Studies and Randomized Trials in Nutrition: An Empirical Evaluation and Citation Analysis
Blogger's Note: a very extensive (long) paper trying to discern factors and results of study findings in nutrition; numerous references to ovarian cancer as per search 'ovarian'
open access
Prepared for:
Agency for Healthcare Research and Quality
U.S. Department of Health and Human Services
540 Gaither Road
Rockville, MD 20850
www.ahrq.gov
"Understanding the translational paths that shape the evidence base may result in insights on why epidemiological and randomized data disagree or agree."
"It is unclear whether there is a good way to describe the maturity of the evidence base on an association between nutrients and outcomes. At a minimum, purely bibliometric approaches are not a good way to prioritize which nutrient exposures merit further study, and for which health outcomes."
Citations:
Koushik A, Hunter DJ, Spiegelman D, et al. Intake of the major carotenoids and the risk of epithelial ovarian cancer in a pooled analysis of 10 cohort studies. Int J Cancer. 2006 Nov 1;119(9):2148-54
Fairfield KM, Hankinson SE, Rosner BA, et al. Risk of ovarian carcinoma and consumption of vitamins A, C, and E and specific carotenoids: A prospective analysis. Cancer 2001;92:2318-26 [Abstract]. PMID: 11745286
Webcast: 19th Annual Meeting of the Network of Oncology Clinicians and Researchers (NOCR) 2013
ELC
Webcast: 19th Annual Meeting of the Network of Oncology Clinicians and Researchers (NOCR) 2013
This webcast from the 19th Annual Meeting of the Network of Oncology
Clinicians and Researchers (NOCR) features comprehensive reviews of the
most clinically significant data in different solid tumor types
including breast, lung, gastrointestinal, genitourinary, gynecologic,
skin, and head and neck cancers. Expert faculty from around the country
will discuss current standards of management and analyze and interpret
the most important new data that has recently modified or has the
potential to modify treatment guidelines and recommendations in these
tumor types. Community oncologists will gain insight from key thought
leaders on breakthroughs in cutting-edge research and advancements in
patient care.
slideset: Dr Robert Coleman - Network of Oncology Clinicians and Researchers conference 2013
Blogger's Note: warning on graphic tumor photos; website requires registation to view (free)
ELC
Slide Sets: How I manage my patients with ovarian cancer
Dr. Robert Coleman presents current recommendations and guidelines
for the management of women with ovarian cancer, including optimal
options for newly-diagnosed disease, maintenance/consolidation phase,
and recurrent disease, and emphasizing the risks and benefits of
investigational agents and regimens.
0 ACCME
Related Activity:
19th Annual Meeting of the Network of Oncology Clinicians and Researchers (NOCR) 2013
Interview: Dr Janicek (gyn oncologist) and Dr Harness (breast) - risks, prevention & recommendations (genetics breast/ovarian/Lynch Syndrome)
Blogger's Note: the missed media opportunity to educate the public regarding important ovarian cancer issues: eg. 1) lack of ovarian cancer effective screening;eg. ovarian cancer is only caught after the fact; 2) ovarian cancer mortality rates are 4x higher than breast cancer; example of hereditary cancer in early ages (20's); 3) breast cancer patients/family history tend to focus on breast cancer only and overlook ovarian cancer; 4) small reference to Lynch Syndrome; 5) barriers to genetic testing; 6) cyberspace myths & false information; 7) twin examples (sisters) and more.....
Distribution of the anticancer drugs doxorubicin, mitoxantrone and topotecan in tumors and normal tissues
Abstract
PURPOSE:
Pharmacokinetic analyses estimate the mean concentration of drug within a given tissue as a function of time, but do not give information about the spatial distribution of drugs within that tissue. Here, we compare the time-dependent spatial distribution of three anticancer drugs within tumors, heart, kidney, liver and brain.METHODS:
Mice bearing various xenografts were treated with doxorubicin, mitoxantrone or topotecan. At various times after injection, tumors and samples of heart, kidney, liver and brain were excised.RESULTS:
Within solid tumors, the distribution of doxorubicin, mitoxantrone and topotecan was limited to perivascular regions at 10 min after administration and the distance from blood vessels at which drug intensity fell to half was ~25-75 μm. Although drug distribution improved after 3 and 24 h, there remained a significant decrease in drug fluorescence with increasing distance from tumor blood vessels. Drug distribution was relatively uniform in the heart, kidney and liver with substantially greater perivascular drug uptake than in tumors. There was significantly higher total drug fluorescence in the liver than in tumors after 10 min, 3 and 24 h. Little to no drug fluorescence was observed in the brain.CONCLUSIONS:
There are marked differences in the spatial distributions of three anticancer drugs within tumor tissue and normal tissues over time, with greater exposure to most normal tissues and limited drug distribution to many cells in tumors. Studies of the spatial distribution of drugs are required to complement pharmacokinetic data in order to better understand and predict drug effects and toxicities.Ovarian Transitional Cell Carcinoma Represents a Poorly Differentiated Form of High-grade Serous or Endometrioid Adenocarcinoma
Abstract
Ovarian transitional cell tumors include Brenner tumors (BTs) and transitional
cell carcinoma (TCC; non-BTs) according to the most recent World Health
Organization classification. However, it remains a matter of debate
whether TCC represents a distinct entity or a morphologic variant of
high-grade serous adenocarcinoma (HG-SC). The purpose of this study was
to resolve the above question by clarifying the morphologic,
immunohistochemical, and molecular features of TCC. We reviewed 488
cases of epithelial ovarian carcinomas and reclassified them on the
basis of the most recent World Health Organization classification with
the modifications proposed by Köbel and colleagues, and 35 cases of TCC
were identified; 25 and 6 TCCs were admixed with HG-SC and endometrioid
adenocarcinoma (EC), respectively, and the remaining 4 cases were pure
TCC. TCC components were not observed in any clear cell carcinomas or
mucinous adenocarcinomas. Only 2 cases of malignant BT were identified.
In addition to TCCs, malignant BTs, and related adenocarcinomas, benign
and borderline BTs were included in the following immunohistochemical
and molecular analyses. Immunohistochemically, pure TCCs, TCCs admixed
with HG-SC, and pure HG-SCs were characterized by frequent aberrant p53
expression (diffuse or null pattern) and WT1/ER/PR/IMP2 immunophenotype,
whereas BTs, including benign, borderline, and malignant BTs, were
characterized by lack of aberrant p53 expression and WT1/ER/PR/IMP2
immunophenotype. In contrast to the BTs, pure ECs and TCCs admixed with
EC showed an ER/PR immunophenotype. Nearly all the tumors with a TP53
gene mutation by molecular analysis showed aberrant p53 staining
patterns. In conclusion, TCC is not a distinct entity but a poorly
differentiated form of serous or EC, as (1) most TCCs coexist with HG-SC
(mostly) or EC (occasionally), and (2) the immunophenotype and
molecular features are similar to those of HG-SC or EC but different
from those of BTs.
ERα-Targeted Therapy in Ovarian Cancer Cells by a Novel Estradiol-Platinum(II) Hybrid
Abstract
As we previously showed, we have
synthesized a new family of 17β-estradiol-platinum(II) hybrids. Earlier
studies revealed
the VP-128 hybrid to show high efficiency compared
with cisplatin toward hormone-dependent breast cancer cells. In the
present
research, we have studied the antitumor activity of
VP-128 in vitro and in vivo against ovarian cancer. In nude mice with
ovarian xenografts, VP-128 displayed selective
activity toward hormone-dependent tumors and showed higher efficiency
than
cisplatin to inhibit tumor growth..............
Altogether these results highlight the beneficial value of VP-128 for
the treatment
of hormone-dependent ovarian cancers and provide
preliminary proof of concept for the efficient targeting of ERα- by
17β-estradiol-Pt(II)-linked
chemotherapeutic hybrids in these tumors.
Correlation of cancer incidence with diet, smoking and socio- economic position across 22 districts of tehran in 2008
Abstract
Background:
Variation in cancer incidence in geographical locations is due to
different lifestyles and risk factors. Diet and socio-economic position
(SEP) have been identified as important for the etiology of cancer but
patterns are changing and inconsistent. The aim of this study was to
investigate correlations of the incidence of common cancers with food
groups, total energy, smoking, and SEP.
Materials and Methods: In an ecological study, disaggregated cancer data through the National Cancer Registry in Iran (2008) and dietary intake, smoking habits and SEP obtained through a population based survey within the Urban Health Equity Assessment (Urban-HEART) project were correlated across 22 districts of Tehran.
Results: Consumption of fruit, meat and dairy products adjusted for energy were positively correlated with bladder, colorectal, prostate and breast and total cancers in men and women, while these cancers were adversely correlated with bread and fat intake. Also prostate, breast, colorectal, bladder and ovarian cancers had a positive correlation with SEP; there was no correlation between SEP and skin cancer in both genders and stomach cancer in men.
Conclusions: The incidence of cancer was higher in some regions of Tehran which appeared to be mainly determined by SEP rather than dietary intake. Further individual data are required to investigate reasons of cancer clustering.
Materials and Methods: In an ecological study, disaggregated cancer data through the National Cancer Registry in Iran (2008) and dietary intake, smoking habits and SEP obtained through a population based survey within the Urban Health Equity Assessment (Urban-HEART) project were correlated across 22 districts of Tehran.
Results: Consumption of fruit, meat and dairy products adjusted for energy were positively correlated with bladder, colorectal, prostate and breast and total cancers in men and women, while these cancers were adversely correlated with bread and fat intake. Also prostate, breast, colorectal, bladder and ovarian cancers had a positive correlation with SEP; there was no correlation between SEP and skin cancer in both genders and stomach cancer in men.
Conclusions: The incidence of cancer was higher in some regions of Tehran which appeared to be mainly determined by SEP rather than dietary intake. Further individual data are required to investigate reasons of cancer clustering.
Salvage Therapy of Gemcitabine Plus Endostar Significantly Improves Progression-free Survival (PFS) with Platinum-resistant Recurrent Epithelial Ovarian Cancer
Abstract
Anti-angiogenic
agents have played crucial roles in the treatment of ovarian cancer in
recent years, but potential benefits of endostatin have been largely
unexplored. The present retrospective study evaluated its efficacy and
toxicity with two cohorts of patients with platinum-resistant recurrent
ovarian cancer. One cohort received gemcitabine plus endostar
(rh-endostatin), and the second cohort received gemcitabine regimen
alone, with totals of 31 and 27 patients, respectively. The main
endpoints were disease control rate (DCR), PFS, overall survival (OS)
and safety. There were statistically significant differences in DCR
(70.9% vs. 40.7%; P = 0.02) and PFS (6.3 months vs. 3.2 months, P =
0.001) between the two cohorts. Though the endostar cohort also improved
median OS by 2.1 months, there was no statistically significant
difference compared with gemcitabine alone cohort in this case (12.5
months vs. 10.4 months, P = 0.201). Treatment was well tolerated for
most patients, and toxicity of endostar was negligible. Gemcitabine plus
endostar significantly improved the prognosis in patients with
platinum-resistant recurrent ovarian cancer, especially in those with
malignant effusion. The endostar- containing regimen is recommended in
this setting.
Incidence, Trends and Morphology of Ovarian Cancer in Karachi (1995-2002)
open access
Conclusions: The incidence of cancer ovary, though stable in Karachi (South Pakistan), involves a relatively younger age group (see Table 1) with a strong family history in a fourth of the cases. The disease presents at an advanced stage. An ageing population over time may translate into a higher incidence of ovarian cancer. The current incidence of cancer ovary in Karachi is an enigma and belies reproductive protective factors. Studies focused on the genetic risk factors in this population are recommended.
Increased elimination of paclitaxel by magnesium isoglycyrrhizinate in epithelial ovarian cancer patients treated with paclitaxel plus cisplatin: a pilot clinical study (ovarian cancer)
Blogger's Note: it would be unusual for a study to be completed only in Stage 11 (due to small numbers); possible typo?; full paper and/or revision may clarify
Abstract
Magnesium isoglycyrrhizinate (MI) has been complementarily used for restoring the
hepatic impairments caused by taxol plus platinum based chemotherapies
in China. Due to the hepatic dependence of paclitaxel elimination, this
pilot clinical study aimed to investigate the influence of MI on the
pharmacokinetics of paclitaxel in epithelial ovarian cancer patients.
During the standard chemotherapy of intravenous paclitaxel (125 mg/m2 infused over a 3-h period) and intraperitoneal cisplatin (60 mg/m2)
for patients with FIGO stage II epithelial ovarian cancer, 9 each of
total 18 patients were respectively treated with intravenous MI (100 mg)
or vehicle control for 4 days. Plasma paclitaxel was analyzed by HPLC
and the pharmacokinetic parameters were calculated with
non-compartmental analysis. The hematological, hepatic and renal status
was monitored before and 3 days after paclitaxel administration. It was
observed the terminal t 1/2 and MRT of paclitaxel were
significantly (p = 0.002 and 0.001) reduced by MI, respectively, from
11.0 ± 2.2 and 5.6 ± 1.0 h to 7.7 ± 1.7 and 4.0 ± 0.3 h. Hematological
toxicity indicated by platelet count and hepatic events marked with ALT,
AST and γ-GT were significant in both groups. In spite of the
insignificance of decreased system exposure of paclitaxel and recovered
hepatic function by MI, they did correlate with each other. It was
therefore deduced that the liver toxicities of paclitaxel plus cisplatin
chemotherapy potentially decrease hepatic elimination and increase
system exposure of paclitaxel, and the recovery of liver function by MI
helps to restore hepatic clearance of paclitaxel. The clinical
significance of this pharmacokinetic interaction requires further
studies with larger population size.
Article in 'Science' says returning genetic incidental findings without patient consent violates basic rights : UMNews : University of Minnesota
genetic incidental findings without patient consent violates basic rights
"MINNEAPOLIS / ST. PAUL (05/16/2013) —Informed consent is the backbone of patient care. Genetic testing has long required patient consent and patients have had a "right not to know" the results. However, as 21st century medicine now begins to use the tools of genome sequencing, an enormous debate has erupted over whether patients’ rights will continue in an era of medical genomics. Recent recommendations from the American College of Medical Genetics and Genomics (ACMG) suggest no. On March 22, the ACMG released recommendations stating that when clinical sequencing is undertaken for any medical reason, laboratories must examine 57 other specific genes to look for incidental findings. These findings must then be reported to the clinician and the patient. In an April 25 "clarification," ACMG said that failure to report these findings would be considered "unethical." The patient has no opportunity to opt-out of the testing of the 57 genes, except to decline all sequencing. The recommendations also apply to children...............
Friday, May 17, 2013
MSF scientific day 2013—how can we measure the impact of research? (blogging, twitter, FB, open access...
Médecins Sans Frontières
".... Virginia Barbour highlighted just how strikingly Facebook and Twitter have made a difference to sharing research. She said that 10% of PLOS papers published in the past decade have been tweeted, and very few have been shared/liked on Facebook. However, compare this with papers published in the past six months, where 100% of papers have been tweeted, and 81% have been shared on Facebook, and you can see what an impact social media now has on promoting and sharing research....
Genetic Risk Assessment for Women with Epithelial Ovarian Cancer: Referral Patterns and Outcomes in a University Gynecologic Oncology Clinic (Minnesota)
Abstract
Little is known about genetic service utilization and ovarian cancer. We identified the frequency and outcome of genetic counseling referral, predictors of referral, and referral uptake for ovarian cancer patients. Using pathology reports, we identified all epithelial ovarian cancer
patients seen in a university gynecologic oncology clinic (1/04-8/06).
Electronic medical records (EMR) were used to document genetic service
referral, time from diagnosis-to-referral, point-in-treatment at
referral, personal/family cancer
history, demographics, and genetic test results. Groups were compared
using chi-squared and Fisher's exact test for categorical variables and
t-tests for continuous variables. The study population consisted of 376
women with ovarian cancer,
72 (19 %) of who were referred for genetic counseling/testing,
primarily during surveillance. Of those referred, 42 (58 %) had personal
or family genetic counseling and 34 (47 %) were ultimately tested or
identified due to known family mutation. Family history and prior cancer
were associated with referral. Family history, living in a larger
community, higher-stage disease, and serous histology were associated
with undergoing genetic counseling. Risk assessment identified 20
BRCA1/2 (5.3 %) and 1 HNPCC (0.3 %) mutation carriers. Based on recent
estimates that 11.7-16.6 % of women with ovarian cancer
are BRCA carriers and 2 % are HNPCC carriers, results suggest
under-identification of carriers and under-utilization of genetic
services by providers and patients. Interventions to increase medical
providers' referrals, even in a specialized oncology clinic, are
necessary and may include innovations in educating these providers using
web-based methods. Ease of referral by the introduction of an
electronic cancer genetic referral form represents another new direction that may increase genetic risk assessment for high-risk women with ovarian cancer.
Thursday, May 16, 2013
Cancer Treatment Reviews - Metabolic complications with the use of mTOR inhibitors for cancer therapy
Abstract
Interpretation
The risk of all
grade and grade 3–4, hyperglycemia, hypercholesterolemia, and
hypertriglyceridemia, are increase in patients treated with mTOR
inhibitors compared with control.
A qualitative study into the difficulties experienced by healthcare decision makers when reading a Cochrane diagnostic test accuracy review
open access
Background
Cochrane reviews are one of the best known and most trusted sources of evidence-based
information in health care. While steps have been taken to make Cochrane intervention
reviews accessible to a diverse readership, little is known about the accessibility
of the newcomer to the Cochrane library: diagnostic test accuracy reviews (DTARs).
The current qualitative study explored how healthcare decision makers, who varied
in their knowledge and experience with test accuracy research and systematic reviews,
read and made sense of DTARs.
Conclusions
The study demonstrates that authors and editors should pay more attention to the presentation
as well as the content of Cochrane DTARs, especially if the reports are aimed at readers
with various levels of background knowledge and experience. It also raises the question
as to the anticipated target audience of the reports and suggests that different groups
of healthcare decision-makers may require different modes of presentation.
The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.
Warning didn't change for-profit dialysis drug use | Reuters
Blogger's Note: as it applies specifically to ovarian cancer or other cancers there exists many related research/articles - published on this blog and elsewhere
Reuters
"The researchers looked at epoetin alfa, which is marketed as Epogen by Amgen, and darbepoetin alfa, which is marketed as Aranesp also by Amgen. In 2007, the U.S. Food and Drug Administration (FDA) issued a black box warning - the strongest kind - to use as little of the ESAs as possible. Research showed higher doses were associated with an increased risk of death, strokes and heart disease......"
Another New Immune Therapy (MPDL3280A ) Effective in Multiple Cancers
Another New Immune Therapy Effective in Multiple Cancers
"The study has been expanded to include blood cancers and a larger range of solid tumors, and now has enrolled 275 patients. MPDL3280A combination studies, including with targeted therapies, have also been initiated, said Dr. Herbst. ......
A tiered-layered-staged model for informed consent in personal genome testing
open access
Introduction
For a few years, a new generation
of so-called personal genome testing (PGT) companies has been marketing
genome-wide SNP analysis and whole genome sequencing directly to
consumers. These companies offer personal risks for dozens of diseases
simultaneously, including cardiovascular diseases, type 2 diabetes,
psychiatric conditions and many types of cancer. (Pathway: https://www.pathway.com; Knome: http://www.knome.com; Counsyl: https://www.counsyl.com; 23andme: http://www.23andme.com; deCODEme: http://www.decodeme.com)
Consumers can obtain this information through web-based services with (Pathway: https://www.pathway.com; Counsyl: https://www.counsyl.com) or without (23andme: http://www.23andme.com; deCODEme: http://www.decodeme.com)
the involvement of a medical professional in the signing off on the
test order. Consumers take a cheek swab sample at home, send their
sample to a molecular genetic testing laboratory through the mail and
receive their genetic test results on a secure personal webpage.
Whole-genome sequencing in health care - Recommendations of the European Society of Human Genetics
Blogger's Note: there are numerous references to 'unsolicited findings' with the explanation of the term given in the article; basically the 'term' is meant to replace or qualify, what is commonly known, as something which is found but not anticipated during care
open access
Recommendations
- In order to contribute to developing best practices in implementing WGS/WES into health care, stakeholders from relevant fields in research and the clinic should set up structures for sharing experiences and establish testing guidelines at local, national and international levels.
- When in the clinical setting either targeted sequencing or analysis of genome data is possible, it is preferable to use a targeted approach first in order to avoid unsolicited findings or findings that cannot be interpreted. Filtering should limit the analysis to specific (sets of) genes. Known genetic variants with limited or no clinical utility should be filtered out (if possible neither analyzed nor reported).
- The use of genome-wide arrays or WGA requires a justification in terms of necessity (the need to solve a clinical problem) and proportionality (the balance of benefits and drawbacks for the patient).
- Whenever the use of these techniques is considered, a protocol has to be in place to give guidance on the reporting of unsolicited findings. If the detection of an unsolicited genetic variant is indicative of serious health problems (either in the person tested or his or her close relatives) that allow for treatment or prevention, in principle, a health-care professional should report such genetic variants.
- Guidelines for informed consent regarding diagnostic testing need to be developed. Patients’ claims to a right not to know do not automatically over-ride professional responsibilities when the patient’s own health or that of his or her close relatives are at stake. Patient groups could provide important input into how this should be handled.
- As testing for health care and for biobank research can be intertwined activities, clinicians should be aware of the importance of safeguarding the patient’s position and explain the potential crossover with research. Relevant normative frameworks including consent procedures for diagnosis, research, disclosure and storage need to be reconsidered, and if necessary adapted to the challenges of the new situation.
- In case of testing minors, guidelines need to be established as to what unsolicited information should be disclosed in order to balance the autonomy and interests of the child and the parental rights and needs (not) to receive information that may be in the interest of their (future) family.
- In the case where new scientific evidence of clinical relevance to patients arises from the initial investigation after a diagnostic question was dealt with, the possibility of recontacting participants should be considered. A guideline should be established detailing how and when this should be done.
- To facilitate the interpretation of genome data, international collaboration is needed to build sustainable databases on genotypic and phenotypic information of variants and patients.
- A sustained effort at genetic education of health-care professionals is required at various levels: in primary care to inform and refer people appropriately, and in specialized care to counsel or refer patients, and to discuss and interpret genetic test results adequately.
- Genetic experts should engage in discussing new developments in genetics, and explain the pros and cons of genetic testing and screening in clinical and commercial settings to inform the public and raise public awareness. Enhancing genetic literacy in patients and the lay public will help to involve wider society in this debate.
conference notice: Patient Safety/Johns Hopkins Armstrong (Baltimore, MD) Sept 2013
Program at a Glance
Who Should Attend
This forum is designed to be a “must” for those who can contribute to the future of this exciting field and for those who want to stay on top of the latest thinking and advances in patient safety science.
- Chief medical, nursing, and quality and patient safety officers from health care delivery organizations
- Scientists and researchers in patient safety and quality improvement
- Thought leaders from all sectors who influence health care, including industry, regulatory, policy-making and insurance
- Leaders of schools for health professions
- Patients and patient-advocacy groups
- Professional associations in medicine and other health-related fields
ASCO - video with Dr Douglas Yee - Chair, Scientific Program Committee 2013
ASCO
Watch the video with Douglas Yee, MD, Chair, of the Scientific Program Committee, as he discusses how the 2013 ASCO Annual Meeting Scientific Program reflects the priorities and issues that affect every oncology professional. Discover the latest in scientific research from over 2,500 abstracts that have been accepted for presentation at the Meeting.
7 updates from pubmed as at May 16th - ovarian cancer
Blogger's Note: Sent on Thursday, 2013 May 16 (some duplicates from previously posted individually to blog)
| PubMed Results |
| 1. | Correction: Potential Role of Estrogen Receptor Beta as a Tumor Suppressor of Epithelial Ovarian Cancer. |
| Bossard C, Busson M, Vindrieux D, Gaudin F, Machelon V, Brigitte M, Jacquard C, Pillon A, Balaguer P, Balabanian K, Lazennec G. | |
| PLoS One. 2013 May 10;8(5). doi: 10.1371/annotation/480acc26-456b-4e06-8cb6-2834bd6f5553. Print 2013. | |
| PMID: 23675394 [PubMed - as supplied by publisher] | |
| 2. | Correction: Associations between Gene Expression Variations and Ovarian Cancer Risk Alleles Identified from Genome Wide Association Studies. |
| Zhao H, Shen J, Wang D, Guo Y, Gregory S, Medico L, Hu Q, Yan L, Odunsi K, Lele S, Liu S. | |
| PLoS One. 2013 May 10;8(5). doi: 10.1371/annotation/febad39e-58f0-4562-a687-1fee2a7d1eff. Print 2013. | |
| PMID: 23675393 [PubMed - as supplied by publisher] | |
| 3. | Multicentre external validation of IOTA prediction models and RMI by operators with varied training. |
| Sayasneh A, Wynants L, Preisler J, Kaijser J, Johnson S, Stalder C, Husicka R, Abdallah Y, Raslan F, Drought A, Smith AA, Ghaem-Maghami S, Epstein E, Van Calster B, Timmerman D, Bourne T. | |
| Br J Cancer. 2013 May 14. doi: 10.1038/bjc.2013.224. [Epub ahead of print] | |
| PMID: 23674083 [PubMed - as supplied by publisher] | |
| 4. | The in vitro antitumor activity of Siegesbeckia glabrescens against ovarian cancer through suppression of receptor tyrosine kinase expression and the signaling pathways. |
| Cho YR, Choi SW, Seo DW. | |
| Oncol Rep. 2013 May 15. doi: 10.3892/or.2013.2468. [Epub ahead of print] | |
| PMID: 23673404 [PubMed - as supplied by publisher] | |
| 5. | The use of CT findings to predict extent of tumor at primary surgery for ovarian cancer. |
| Glaser G, Torres M, Kim B, Aletti G, Weaver A, Mariani A, Hartmann L, Cliby W. | |
| Gynecol Oncol. 2013 May 11. doi:pii: S0090-8258(13)00740-3. 10.1016/j.ygyno.2013.05.007. [Epub ahead of print] | |
| PMID: 23672930 [PubMed - as supplied by publisher] | |
| 6. | Optimal (≤ 1cm) but Visible Residual Disease: Is Extensive Debulking Warranted? |
| Barlin JN, Long KC, Tanner EJ, Gardner GJ, Leitao MM, Levine DA, Sonoda Y, Abu-Rustum NR, Barakat RR, Chi DS. | |
| Gynecol Oncol. 2013 May 11. doi:pii: S0090-8258(13)00739-7. 10.1016/j.ygyno.2013.05.006. [Epub ahead of print] | |
| PMID: 23672929 [PubMed - as supplied by publisher] | |
| 7. | Chemoresistance in ovarian cancer linked to expression of microRNAs. |
| Frederick P, Green H, Huang J, Egger M, Frieboes H, Grizzle W, McNally L. | |
| Biotech Histochem. 2013 May 15. [Epub ahead of print] | |
| PMID: 23672416 [PubMed - as supplied by publisher] |
(drug) Safety Information > April 2013
Safety Information > April 2013
April 2013
The summary view includes drug products with safety labeling changes to the BOXED WARNING, CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, ADVERSE REACTIONS, or PATIENT PACKAGE INSERT/MEDICATION GUIDE sections. The “quick view” table below provides the drug name and sections modified. Click on the drug name to go to the detailed view. The detailed view includes sections and subsections modified, a description of new or modified safety information in the BOXED WARNING, CONTRAINDICATIONS, or WARNINGS sections, and a link to the revised prescribing information.
Key to Label Section Acronyms:
BW=BOXED WARNING, C=CONTRAINDICATIONS, W=WARNINGS, P=PRECAUTIONS
AR=ADVERSE REACTIONS, PPI/MG=PATIENT PACKAGE INSERT/MEDICATION GUIDE
AR=ADVERSE REACTIONS, PPI/MG=PATIENT PACKAGE INSERT/MEDICATION GUIDE
(2nd article re: costs)Study finds broader set of concerns for improving quality of life
Study - medical news
"...Even drugs that confer only incremental gains in survival, however, were found to be worth covering in the eyes of all groups surveyed: Just 12 percent of physicians were willing to refuse payment for a drug that extends life by four months, compared to 20 percent of patients and 28 percent of the general public........
Case Reports - Successful Treatment with Nab-paclitaxel after Hypersensitivity Reaction to Paclitaxel and Docetaxel
open access
Highlights
- •
- First case report of successfully treating severe paclitaxel and docetaxel hypersensivity reaction with nab-paclitaxel.
- •
- We demonstrated that nab-paclitaxel is a safe taxane chemotherapy treatment option for patients who could not tolerate paclitaxel or docetaxel.
Introduction
The
standard treatment for patients with ovarian cancer is the combination
of platinum and taxane chemotherapy.. However, one of the limitations in
using paclitaxel and docetaxel is the hypersensitivity reaction (HSR)
that patients’ experience. Despite pretreatment during initial infusion
severe HSR could occur in 2% of the cases. For patients who develop HSR
to paclitaxel there is the danger of cross reactivity with docetaxel and
has been reported to be as high as 90% as previously published by Dizon
et al. [1].
The
etiology of HSR to paclitaxel and docetaxel is poorly understood. It is
believed that the solvent Cremophor EL in paclitaxel, and polysorbate80
in docetaxel may be the cause of HSR. Yet, others have demonstrated
that HSR maybe secondary to the direct effect of the taxane itself [2] and not the diluents. There have been several reports that nab-paclitaxel can be safely administered after HSR to paclitaxel [3] but no reported cases of safely administering nab-paclitaxel after HSR to both paclitaxel and docetaxel.
Case Report:
This
is a 60 year old female who presented with abdominal pain and bloating.
A CT scan of abdomen and pelvis in 7/2012 showed ascites, 16 cm complex
pelvic mass and omental caking. In 9/2012 she was brought to the
operating room for tumor debulking, however intraoperatively she became
hypotensive and unstable. Only partial omentectomy could be performed
and pathology was consistent with serous carcinoma from ovarian primary.
Phase II Study of Ipilimumab Monotherapy in Recurrent Platinum Sensitive Ovarian Cancer Patients
Full Text View
This study is currently recruiting participants.
Verified December 2012 by Bristol-Myers Squibb
Sponsor:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01611558
First received: May 25, 2012
Last updated: December 7, 2012
Last verified: December 2012
ASCO: Immune Therapy Wins Praise
ASCO: Immune Therapy
"...Herbst reported findings for 171 patients, 140 of whom could be evaluated for response. The study population included patients with lung cancer, kidney cancer, melanoma, colon cancer, stomach cancer, and head and neck cancer, and the patients had received a median of five prior therapies. .....
Action Points
Arts Therapy Has Benefits in Cancer
Arts Therapy
Action Points
- Note that this systematic review of the literature revealed an association between creative arts therapies and improved quality of life in cancer patients.
- Be aware that the significant heterogeneity in these studies makes it difficult to recommend creative arts therapies for all cancer patients; a large clinical trial may be necessary.
PARP Inhibitor Shows Activity in Pancreatic, Prostate Cancers Among Patients Carrying BRCA Mutations
PARP Inhibitor
PHILADELPHIA – In the largest clinical trial to date to examine the efficacy of PARP inhibitor therapy in BRCA 1/2 carriers with diseases other than breast and ovarian cancer, the oral drug olaparib was found to be effective against advanced pancreatic and prostate cancers. Results of the study, led by researchers from the Perelman School of Medicine at the University of Pennsylvania and Sheba Medical Center in Tel Hashomer, Israel, will be presented during the American Society of Clinical Oncology’s annual meeting in Chicago in early June (Abstract #11024)...........
Study Finds Broad Support for Rationing of Some Types of Cancer Care (media/asco link/other)
Blogger's Note: read the full text for context
media
Newswise — PHILADELPHIA – The majority of cancer doctors, patients, and members of the general public support cutting health care costs by refusing to pay for drugs that don’t improve survival or quality of life, according to results of a new study that will be presented by researchers from the Perelman School of Medicine at the University of Pennsylvania during the annual meeting of the American Society of Clinical Oncology in Chicago in early June (Abstract #6518).
The Penn Medicine team surveyed 326 adult cancer patients receiving treatment at Penn’s Abramson Cancer Center, a random sample of 891 adults in the general public, and 250 oncologists across the United States during 2012 to probe their opinions about tactics for controlling costs associated with cancer care......
Other Abstracts in this Sub-Category:
| 1. Financial distress, communication, and cancer treatment decision making: Does cost matter? Meeting: 2013 ASCO Annual Meeting Abstract No: 6506 First Author: Y. Zafar Category: Health Services Research - Cost | |
| 2. Determining value of high cost cancer therapies and discussing cost of cancer care: The patient perspective. Meeting: 2013 ASCO Annual Meeting Abstract No: 6512 First Author: S. Rajguru Category: Health Services Research - Cost | |
| 3. Adoption of robot-assisted surgery and its impact on treatment patterns for newly diagnosed localized prostate cancer. Meeting: 2013 ASCO Annual Meeting Abstract No: 6513 First Author: Y. T. Shih Category: Health Services Research - Cost |
Survey on Data Reproducibility in Cancer Research Provides Insights into Our Limited Ability to Translate Findings from the Laboratory to the Clinic
open access
Background
The pharmaceutical and biotechnology industries depend on findings from academic investigators prior to initiating programs to develop new diagnostic and therapeutic agents to benefit cancer patients. The success of these programs depends on the validity of published findings. This validity, represented by the reproducibility of published findings, has come into question recently as investigators from companies have raised the issue of poor reproducibility of published results from academic laboratories. Furthermore, retraction rates in high impact journals are climbing.Methods and Findings
To examine a microcosm of the academic experience with data reproducibility, we surveyed the faculty and trainees at MD Anderson Cancer Center using an anonymous computerized questionnaire; we sought to ascertain the frequency and potential causes of non-reproducible data. We found that ~50% of respondents had experienced at least one episode of the inability to reproduce published data; many who pursued this issue with the original authors were never able to identify the reason for the lack of reproducibility; some were even met with a less than “collegial” interaction.Conclusions
These results suggest that the problem of data reproducibility is real. Biomedical science needs to establish processes to decrease the problem and adjudicate discrepancies in findings when they are discovered.".....Recently, the New York Times published an article about the rise of retracted papers in the past few years compared to previous decades [3]. The article states that this larger number may simply be a result of increased availability and thus scrutiny of journal articles due to web access. Alternatively, the article highlighted that the increase in retractions could be due to something much worse; misconduct by investigators struggling to survive as scientists during an era of scarce funding. This latter explanation is supported by another study, which suggested that the most prevalent reason for retraction is misconduct. In their review of all retracted articles indexed in Pubmed (over 2,000 articles) these authors discovered that 67.4% of retracted articles had been retracted due to misconduct [4]. Regardless of the reasons for the irreproducible data, these inaccurate findings may be costing the scientific community, and the patients who count on its work, time, money, and more importantly, a chance to identify effective therapeutics and biomarkers based on sound preclinical work...........
' venous thromboembolism (VTE)' Search Results| 2013 ASCO
Abstracts
Find EXACT phrase: venous thromboembolism (VTE)
Found 9 documents, showing 1 - 9.
- Venous
thromboembolism in advanced ovarian cancer patients undergoing
front-line adjuvant chemotherapy. | 2013 ASCO Annual Meeting Abstracts
... significance of venous thromboembolism (VTE) in patients with advanced, epithelial ovarian ...
- The
incidence, risk factors and prognostic implications of venous
thromboembolism in Asian patients with non-small cell lung cancer. |
2013 ASCO Annual Meeting Abstracts
... implications of venous thromboembolism (VTE) in Asian patients with non-small cell lung ...
- A
prospective study on the incidence of postoperative venous
thromboembolism in Korean gastric cancer patients: An inquiry into the
application of western guidelines to Asian cancer patients. | 2013 ASCO
Annual Meeting Abstracts
... to prevent venous thromboembolism (VTE). However, the necessity of routine pharmacologic ...
- Risk of arterial (ATE) and venous thromboembolism (VTE)
in a population-based cohort of bevacizumab-treated metastatic
colorectal cancer (mCRC) patients. | 2013 ASCO Annual Meeting Abstracts
... arterial (ATE) and venous thromboembolism (VTE) in a population-based cohort of bevacizumab-...
- Risk factors for venous thromboembolism in elderly patients with glioblastoma. | 2013 ASCO Annual Meeting Abstracts
... : Background: Venous thromboembolism (VTE) is a common complication in glioblastoma (GBM) ...
- Chemotherapy-associated
thrombosis in cancer outpatients: Risk factors and decision making of a
prophylactic approach. | 2013 ASCO Annual Meeting Abstracts
... : Background: Venous thromboembolism (VTE), is a negative predictor of survival in pts with ...
- Prothrombotic
profile in multiple myeloma: Response to treatment and associated
thrombotic complications: A prospective observational study. | 2013 ASCO
Annual Meeting Abstracts
... : Background: Venous thromboembolism (VTE) is a major complication of Multiple myeloma. The ...
- Low
molecular weight heparin (LMWH) for primary thrombophylaxis in patients
with solid malignancies: Systematic review and meta-analysis. | 2013
ASCO Annual Meeting Abstracts
... increased risk for venous thromboembolism (VTE). The role of low molecular weight heparin (LMWH) ...
- Randomized,
placebo controlled, phase III trial of low-dose tamoxifen in women with
intraepithelial neoplasia. | 2013 ASCO Annual Meeting Abstracts
... cancer and of venous thromboembolism (VTE). We recently showed that a dose of 5 mg/day does ...
Bankruptcy Rate Doubles With Cancer Diagnosis
Medscape
"Adults diagnosed with cancer are 2.65 times more likely to declare bankruptcy than adults without cancer, according to a new study.
In addition, bankruptcy rates are 2- to 5-fold higher among younger cancer patients than among older cancer patients, report the study authors, led by Scott Ramsey, MD, PhD, an internist and health economist at the Fred Hutchinson Cancer Research Center in Seattle, Washington.........
Potential of patient-reported outcomes as nonprimary endpoints in clinical trials
Blogger's Note: this paper is not specific to ovarian cancer
open access
Conclusions
Successful PRO (patient reported outcomes) labeling claims are typically based on primary endpoints assessing signs and symptoms. Based on this research, studies with PROs as primary endpoints are far more likely to facilitate positive regulatory review and acceptance of PROs in support of labeling claims. Although inclusion of PROs as nonprimary endpoints in clinical trials has its challenges, recent PRO labels granted by the FDA show that they can indeed be candidates for PRO labeling claims as long as they are supported by evidence.
Authors:
1 Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ, USA
2 Health Solutions, 200 Park Offices Drive, Research Triangle Park, NC 27709, USA
3 RTI Health Solutions, 3005 Boardwalk St., Suite 105, Ann Arbor, MI 48108, USA
Validating the M. D. Anderson Symptom Inventory (MDASI) for use in patients with ovarian cancer
Abstract
Highlights
- •
- The M. D. Anderson Symptom Inventory (MDASI) assesses patient-reported symptoms.
- •
- We validated a MDASI module for use in patients with ovarian cancer (MDASI-OC).
- •
- The MDASI-OC is psychometrically valid, reliable, and sensitive to symptom change.
Objective
The
M. D. Anderson Symptom Inventory (MDASI) captures the severity of
common cancer symptoms from the patients’ perspective. We describe the
validity and sensitivity of a module of the MDASI to be used with
patients having ovarian cancer (MDASI-OC).
Methods
Ovarian
cancer–specific module items were developed from 14 qualitative patient
interviews. 128 patients with invasive epithelial ovarian, peritoneal,
or fallopian-tube cancer treated at MD Anderson Cancer Center were
recruited. Patients completed the MDASI-OC, socio-demographic
questionnaires, the Functional Assessment of Cancer Therapy-Ovary
(FACT-O), and a global quality-of-life (QOL) item. Reliability was
assessed using Cronbach α and sensitivity using known group was
assessed. Construct validity was tested using exploratory factor
analysis.
Results
The sample was
primarily white (85.2%), had a mean age of 57.5 years (± 12.7 years),
and had previously been treated with chemotherapy (75.0%) and/or surgery
(93.8%). Approximately 30% of patients reported disturbed sleep,
fatigue, or numbness/tingling of at least moderate severity (≥ 5 on a
0–10 scale). On the ovarian-cancer-specific symptoms, approximately 20%
reported back pain, feeling bloated, or constipation of at least
moderate severity. Factor analysis revealed six underlying constructs
(pain/sleep; cognitive; disease-related and numbness; treatment-related;
affective; gastrointestinal-specific). MDASI-OC symptom and
interference items had Cronbach α values of 0.90 and 0.89, respectively.
The MDASI-OC was sensitive to symptom severity by performance status
(p=0.009), QOL (p=0.002), and FACT-O scores (p<0.001).
Conclusions
The
27-item MDASI-OC meets common criteria for validation and reliability
and is sensitive to expected changes in symptoms related to differences
in disease and treatment status.
Case Reports - Ovarian carcinoma in situ of presumable fallopian tube origin in a patient with Lynch syndrome (fallopian tube
Conclusion
We reported a rare case of ovarian carcinoma in situ, with a p53 signature, originating from the fallopian tube epithelium and the coexistence of serous ovarian carcinoma in situ and serous borderline tumor in a LS patient. (subsequent to total colectomy)
Highlights
- •
- Occult ovarian carcinoma of presumable fallopian tube origin in Lynch syndrome
- •
- Atypical endometrial hyperplasia during a 10-year follow-up period after colon cancer
- •
- Synchronous ovarian serous carcinoma in situ and borderline tumor in Lynch syndrome
Introduction
Tubal
intraepithelial carcinoma (TIC) has been proposed to be a precursor
lesion of ovarian carcinoma based on studies of risk-reducing
salpingo-oophorectomy (RRSO) specimens from hereditary breast and
ovarian cancer patients [1]. On the other hand, one case of TIC has been
reported in a patient with Lynch syndrome (LS) [2]. Furthermore,
atypical proliferative (borderline) serous tumors account for only 4% of
ovarian carcinomas in patients with LS. Detection of early-stage
ovarian and fallopian tube cancers is difficult even with close
follow-up of high-risk patients with LS [2–5]. This has complicated the
identification of ovarian carcinomas of fallopian tube origin in
patients with LS. Herein, we present a case of ovarian carcinoma in situ that presumably originated from the fallopian tube in a LS patient.
Case
A
34-year-old multipara woman was diagnosed with sigmoid colon cancer and
underwent total colectomy. Her family history matched the Bethesda
criteria for LS. Genetic testing showed the presence of a pathogenic
MLH1 mutation (Exon3: IVS3 + 1 g>a)............ Although the advantages of total abdominal hysterectomy (TAH) with
preventive bilateral salpingo-oophorectomy (BSO) were explained and this
approach was recommended by cancer genetics professionals, the patient
strongly desired preservation of the ovaries in the absence of an
intraoperative malignancy diagnosis...........The patient did not wish to receive adjuvant chemotherapy. She is
currently alive without evidence of disease 22 months after TAH/BSO.Conclusion
We reported a rare case of ovarian carcinoma in situ, with a p53 signature, originating from the fallopian tube epithelium and the coexistence of serous ovarian carcinoma in situ and serous borderline tumor in a LS patient.
Wednesday, May 15, 2013
AAN: Surgical Menopause Tied to Brain Deficits (cognitive decline)
Medpage
........"Our findings support a growing literature on the impact of surgical menopause on cognitive decline function, and add granularity to these outcome measures," Bove said, adding that future studies should include an ongoing look at modifying factors, such as HRT.
Bove also noted that their study was limited by patients who did not have dementia at baseline, which may represent an exclusion bias. Additional limitations included cognitive outcomes that were weighted towards memory; self-reporting by participants, retrospective, limited reproductive histories; and unlisted covariates, such as body mass index.
The study was funded by the NIH.
Some study authors reported relationships (consulting, speakers' fees, financial support) with AVID Radiopharmaceuticals, Eli Lilly, Danone, Dr. Wilmar Schwabe GmbH KG Pharmaceuticals, Eli Lilly, Merck Serono, Teva Neuroscience, and Biogen Idec.
Some study authors reported relationships (consulting, speakers' fees, financial support) with AVID Radiopharmaceuticals, Eli Lilly, Danone, Dr. Wilmar Schwabe GmbH KG Pharmaceuticals, Eli Lilly, Merck Serono, Teva Neuroscience, and Biogen Idec.
First World Ovarian Cancer Day in focus — Dr Sharon O'Toole discusses ovarian cancer (research)
medical news
Dr Sharon O’Toole, Senior Scientist in TCD and the DISCOVARY consortium, outlines the progress made on the diagnosis, treatment and management of ovarian cancer
'serous ovarian' Search Results 2013 ASCO Annual Meeting
Search Results
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'BRCA' Search Results 2013 ASCO Annual Meeting
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"Ureter' Search Results 2013 ASCO Annual Meeting
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Found 4 documents, showing 1 - 4.
Find EXACT phrase: upper tract urothelial
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'Lynch Syndrome' Search Results 2013 ASCO Annual Meeting
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'ovarian cancer' Search Results 2013 ASCO
Search Results
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2013 ASCO Annual Meeting Abstracts - now online
2013 ASCO
2013 ASCO Annual Meeting abstracts
Abstracts published in the Annual Meeting Proceedings Part I will be available on this site at 6:00 PM EDT May 15, 2013. Plenary Abstracts, Late-Breaking Abstracts, and Clinical Review Abstracts (published in the Annual Meeting Proceedings Part II) will be available at 7:30 AM EDT on the date of their presentation at the 2013 ASCO Annual Meeting.
Ovarian cancer among 8,005 women from a breast cancer family history clinic: no increased risk of invasive ovarian cancer in families testing negative for BRCA1 and BRCA2 (repost)
Abstract
- Published Online First 28 March 2013
Background Mutations in BRCA1/2 genes confer ovarian, alongside breast, cancer risk. We examined the risk of developing ovarian cancer in BRCA1/2-positive families and if this risk is extended to BRCA negative families.
Patients and Methods
A prospective study involving women seen at a single family history
clinic in Manchester, UK. Patients were excluded if they
had ovarian cancer or oophorectomy
prior to clinic. Follow-up was censored at the latest date of:
31/12/2010; ovarian cancer
diagnosis; oophorectomy; or death.
We used person-years at risk to assess ovarian cancer rates in the study
population, subdivided
by genetic status (BRCA1, BRCA2, BRCA negative, BRCA untested) compared with the general population.
Results We studied 8005 women from 895 families. Women from BRCA2 mutation families showed a 17-fold increased risk of invasive ovarian cancer (relative risk (RR) 16.67; 95% CI 5.41 to 38.89).
This risk increased to 50-fold in women from families with BRCA1 mutations (RR 50.00; 95% CI 26.62 to 85.50). No association was found for women in families tested negative for BRCA1/2, where there was 1 observed invasive ovarian cancer in 1613 women when 2.74 were expected (RR 0.37; 95% CI 0.01 to 2.03).
There was no association with ovarian cancer in families untested for BRCA1/2 (RR 0.99; 95% CI 0.45 to 1.88).
Discussion This study showed no increased risk of ovarian cancer in families that tested negative for BRCA1/2 or were untested. These data help counselling women from BRCA1/2 negative families with breast cancer that their risk of invasive ovarian cancer is not higher than the general population.
Diagnostic accuracy of preoperative alpha-fetoprotein as an ovarian tumor marker in children and adolescents: not as good as we thought? (infants excluded)
Abstract
Purpose
To evaluate the
diagnostic accuracy of preoperative serum alpha-fetoprotein (AFP) levels
in predicting malignancy risk in children and adolescents presenting
with ovarian neoplasms.
Methods
In 110 girls aged 18
and below diagnosed with ovarian neoplasms, we retrospectively
correlated preoperative serum AFP levels with histological diagnosis of
germ cell tumor or immature teratoma (GCT/IT) versus non-GCT/IT, and
benign versus non-benign. We determined area under receiver-operating
characteristic curves (AUC), sensitivity, specificity, and likelihood
ratios.
Results
Twenty patients
(18.2 %) had non-benign ovarian neoplasms, of which 12 had GCT/IT
(10.9 %). In diagnosing GCT/IT versus non-GCT/IT, specificity of
preoperative serum AFP was 87.8 %, sensitivity 66.7 %, and AUC 0.853.
Excluding infants to remove the effects of increased variance in AFP in
this group, specificity improved (92.0 %), but not sensitivity (66.7 %);
AUC was 0.926. Increasing AFP cutoff to two times upper normal limit
improved specificity (94.9 %), but not sensitivity (66.7 %). For benign
versus non-benign tumors, AFP specificity was only 88.9 % and
sensitivity 50.0 %.
Conclusion
The diagnostic
accuracy of preoperative serum AFP for detecting GCT/IT in girls was
limited by poor sensitivity and positive predictive value. Excluding
infants and raising cutoff levels improved specificity marginally.
Clinicians should be aware of these limitations when using AFP in the
preoperative evaluation of childhood ovarian neoplasms.
Functional genomics identifies five distinct molecular subtypes with clinical relevance and pathways for growth control in epithelial ovarian cancer
open access
".......Although the molecular mechanisms linking TUBGCP4 or NAT10 with Stem-A growth remains to be elucidated, susceptibility to vincristine and vinorelbine underscores the importance of tubulin polymerization in Stem-A cells. Both drugs are well-established chemotherapeutic agents that block cell proliferation by inhibiting microtubule assembly through its interaction with tubulin heterodimers (Lobert et al, 1996); however, they are not standard chemotherapeutic reagents for the treatment of EOC, unlike paclitaxel (Armstrong et al, 2006; McGuire et al, 1996). The molecules implicated in the tubulin polymerization pathway may provide us with a potential platform to more effectively target Stem-A ovarian cancer. As such, the survival of patients with ovarian cancer could be improved by the stratification and targeting strategy described in this study."
A Young Woman With Bilateral Breast Cancer: Identifying a Genetic Cause and Implications for Management (BRCA1/2; Li-Fraumeni syndrome....)
Blogger's Note: of interest to those who may have had negative genetic testing results but with family histories of differing cancers; ovarian cancer is also a risk factor for LFS but potentially underreported in this syndrome
open access
"... Women with LFS have a greater than 90% lifetime risk of cancer,9 and most commonly develop sarcomas (bone and soft tissue), premenopausal breast cancer, acute leukemia, brain tumors, adrenocortical carcinoma, choroid plexus carcinoma, colon and pancreatic cancer, or melanoma.7,10,11.....
Phenotypic heterogeneity of hereditary gynecologic cancers (BRCA1, BRCA2, MLH1, MSH2, MSH6)
Abstract
"To determine the
validity of observations suggesting a significant dichotomy of
gynecologic cancers determined by linkage to specific genetic defects
associated with two major autosomal dominant hereditary cancer
syndromes; the Creighton University Hereditary Cancer Registry was
searched for female carriers of germ line mutations in BRCA1 and BRCA2, associated with the Hereditary Breast Ovarian Cancer syndrome, and in the mismatch repair (MMR) genes MLH1, MSH2 and MSH6,
associated with Lynch syndrome, who were registered with invasive
uterine, ovarian, fallopian tube or peritoneal cancers between January
1, 1959 and December 31, 2010. From 217 such cases, a total of 174
subjects, consisting of 95 BRCA1 and BRCA2
mutation carriers and 79 carriers of mutations in MMR genes, were
identified who had current signed Health Insurance Portability and
Accountability Act forms and complete primary diagnostic pathology
reports and clinical records. Data meticulously extracted from these
cases were categorized and statistically analyzed. There were highly
significant differences between carriers of BRCA1 and BRCA2
mutations and carriers of MMR gene mutations in the proportion of
serous carcinomas compared with endometrioid carcinomas of the uterus,
including cervix and endometium (p < 0.002), ovaries (p < 0.001) and overall, including fallopian tube and peritoneum cancers (p < 0.001). Endometrioid carcinoma was found in one and transitional carcinoma in another of the 14 BRCA1
mutation carriers with fallopian tube cancer, and endometrioid
carcinoma was found in two of four MMR gene mutation carriers with
fallopian tube cancers. All other fallopian tube cancers were serous
carcinomas. Seven BRCA1 and one BRCA2
mutation carriers were diagnosed with primary peritoneal serous
carcinoma; no peritoneal carcinomas were registered in MMR gene mutation
carriers. Nine of 14 gynecologic cancers with associated endometriosis
in mutation carriers were endometrioid or endometrioid mixed carcinomas
compared with just three of other histologic types. Primary breast
cancers, that characterize the HBOC syndrome, were much more frequent in
BRCA1 and BRCA2
mutation carriers; while multiple gynecologic cancers and associated
colorectal and urinary tract cancers, which are features of Lynch
syndrome, were more common in MMR gene mutation carriers. Both serous
and endometrioid carcinomas were diagnosed in MMR gene mutation carriers
at significantly younger ages than in BRCA1 and BRCA2 mutation carriers (p < 0.0006).
These findings confirm a clear dichotomy of uterine, ovarian and
fallopian tube cancers associated with inheritance of mutations in BRCA1 and BRCA2
contrasted with inheritance of MMR gene mutations. This opens
possibilities for new approaches to molecular genetic research into
carcinogenic pathways and raises important new considerations regarding
counseling, screening, prophylaxis and treatment of mutation carriers.
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