Wednesday, June 09, 2010
Endocrine tumors of the appendix: a pathologic review
Abstract
CONTEXT: Although rare, appendiceal endocrine tumors are the most common neoplasms of the appendix. Pathologic analysis is important for guiding the management of patients.
OBJECTIVE: To provide recent data that focus on the pathology of endocrine tumors of the appendix including classifications and guidelines for patient management.
DATA SOURCES: A review of the recent literature including TNM classifications and patient management guidelines.
CONCLUSIONS: Appendiceal endocrine tumors are separated into 2 main groups: classic endocrine tumors and goblet cell carcinoids. They can be classified according to World Health Organization and TNM classifications. Evaluation of their prognoses and risks of malignancy, according to these classifications, depends on several parameters including tumor size, proliferation rate, and infiltration of appendiceal wall and mesoappendix. Most patients with classic endocrine tumors of the appendix have a favorable prognosis. Indications for postappendectomy, complementary surgery, which are still controversial, especially for tumors between 1 and 2 cm, are presented and discussed. In contrast, in patients presenting with a goblet cell carcinoid, a right hemicolectomy after the initial appendectomy is considered the standard surgical intervention.
Appendiceal mucinous neoplasms: controversial issues - pathology
Abstract:
"...reviewed is the largely resolved controversy about whether ovarian mucinous tumors in this setting are separate primaries or are metastases from the appendiceal tumor."
June 8, 2010 SGO Statement on GOG 218 Phase III Trial Study Results (Avastin)
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Scaling Laws for Plasma Concentrations and Tolerable Doses of Anticancer Drugs -- Cancer Research
Abstract:
General scaling laws are developed for projecting measurements of the plasma concentrations of anticancer drugs from laboratory animals to humans and among humans of different sizes. Associated scaling laws for critical drug doses are established from these laws. Broad categories of single and periodic i.v. bolus dosings are considered. Validity of the relations is shown using measurement from the literature for several well-known cytotoxic agents. The scaling theory is also shown to apply to novel anticancer drugs now available or presently under development, as represented by the p.o. administered prodrug capecitabine, the gene silencing inhibitor zebularine, and the blood vessel inhibitor bevacizumab(Avastin). Scaling considerations for the modern practice of combination chemotherapy are also discussed.
JAMA -- Abstract: Genome-wide Analysis of Genetic Loci Associated With Alzheimer Disease, May 12, 2010
"Conclusions Two genetic loci for AD were found for the first time to reach genome-wide statistical significance. These findings were replicated in an independent population. Two recently reported associations were also confirmed. These loci did not improve AD risk prediction. While not clinically useful, they may implicate biological pathways useful for future research."
Future Oncology - Summary - Different volatile signals emitted by human ovarian carcinoma and healthy tissue
Note: in plain english this refers to a small study using 'electronic' smelling (eg. past articles regarding dogs with the ability to 'smell' ovarian cancer)
Future Oncology -- Full Text - Cancer immunotherapy: focusing on the young, neglecting the old
"...Undoubtedly we should pay more attention to the effect that aging has on the immune system. To optimally stimulate an anti-tumor immune response in the old, it is necessary to identify and understand the intrinsic defects of the old immune system and use relevant models that closely reflect those of cancer patients, where self-tolerance and aging are present simultaneously. Then it will be possible to develop cancer immunotherapeutic strategies that are customized to be effective in the young and the old."
Tuesday, June 08, 2010
One to 2-Year Surveillance Intervals Reduce Risk of Colorectal Cancer in Families With Lynch Syndrome
Background & Aims
Two percent to 4% of all cases of colorectal cancer (CRC) are associated with Lynch syndrome. Dominant clustering of CRC (non-Lynch syndrome) accounts for 1%–3% of the cases. Because carcinogenesis is accelerated in Lynch syndrome, an intensive colonoscopic surveillance program has been recommended since 1995. The aim of the study was to evaluate the effectiveness of this program.
Conclusions
With surveillance intervals of 1–2 years, members of families with Lynch syndrome have a lower risk of developing CRC than with surveillance intervals of 2–3 years. Because of the low risk of CRC in non-Lynch syndrome families, a less intensive surveillance protocol can be recommended.
Anti-MUC1 Antibodies and Ovarian Cancer Risk: Prospective Data from the Nurses' Health Studies — Cancer Epidemiology, Biomarkers & Prevention
Conclusion: Anti-MUC1 antibodies evaluated several years before diagnosis may be associated with lower risk of subsequent ovarian cancer in women <64 years old at assessment.
Impact: Key elements of an “immune model” to explain ovarian cancer risk factors are confirmed and should be evaluated in larger prospective studies.
Monday, June 07, 2010
Costly Cancer Treatments Zero In On Disease Niches With Mixed Results : NPR
And the progress being made is costly. Take, for instance, the use of Avastin to slow the growth of ovarian tumors by about four months — at a cost of around $72,000.
“Many would not consider this cost effective for the gain seen,” said Dr Elizabeth A. Eisenhauer of the Canada's National Cancer Institute, according to the New York Times.
Voreloxin - Sunesis Announces Data From Phase 2 Clinical Program of Voreloxin in Acute Myeloid Leukemia Support Phase 3 Trial in Relapsed or Refractory Patients - plus Ovarian Cancer
"Responses to single agent voreloxin observed in women with ovarian cancer for whom multiple prior therapies have failed, including some for whom both platinum-based chemotherapy and Doxil(R) had failed, are promising," said Hal Hirte (medical oncologist), M.D., Associate Professor, McMaster University, Department of Oncology and Chief of Oncology, Juravinski Cancer Centre at Hamilton Health Sciences (Ontario, Canada) and an investigator for the Phase 2 clinical trial. "These data warrant further investigation of voreloxin in this vastly underserved patient population, both in this later stage, salvage setting and in earlier lines of therapy."
Cancer gene patent faces legal challenge - BRCA patients/Australia
"...A legal challenge to the validity of an Australian patent for breast and ovarian cancer genes will be launched in the Federal Court on Tuesday.
The patent for the BRCA1 and BRCA2 genes, which make women more suceptible to the cancers, is owned by American biotechnology company Myriad Genetics. Melbourne-based company Genetic Technologies Limited (GTL) has the exclusive licence from Myriad to carry out testing for the genes in Australia. But law firm Maurice Blackburn is filing a case in the Federal Court in Sydney, challenging the right of the companies to hold exclusive rights to the gene...."
ASCO: Debulking Predicts Survival in Recurrent Ovarian Cancer - in Meeting Coverage, ASCO
"Our analysis represents the first study investigating the relevance of primary surgical outcome for survival after recurrence in ovarian cancer," Mahner and colleagues concluded in their poster presentation. "Our data show that the prognostic importance of initial surgery extends beyond initial treatment to recurrent disease, particularly for patients who have a platinum-free interval of more than 12 months."
Action Points
- Explain to interested patients that an analysis of three large trials found that successful primary surgery increased progression-free and overall survival in ovarian cancer patients who had been platinum-free for at least 12 months.
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
Transdermal and oral hormone replacement therapy and the risk of stroke: a nested case-control study
Conclusions The use of transdermal HRT containing low doses of oestrogen does not seem to increase the risk of stroke. The presence of residual confounding, however, cannot be entirely excluded in the interpretation of this finding.
Gyn Clinical Spotlights | prIME Oncology
7 JUNE 2010
These Clinical Spotlight interviews, with accompanying eNewsflash and downloadable slides, discuss the topic of targeting angiogenesis in the treatment of ovarian cancer with a focus on the following data release:
#LBA1: Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC): A Gynecologic Oncology Group study
The first interview is an expert analysis with Gini Fleming, MD, from the University of Chicago, Illinois in the United States, and Bradley Monk, MD, from the University of California Irvine, Orange, California, United States
The second interview is a supplemental perspective and discussion with Bradley Monk, MD, from the University of California Irvine, Orange, California, United States, and Michael Birrer, MD, PhD, from the Massachusetts General Hospital, Boston, Massachusetts in the United States.
View the expert analysis with Gini Fleming, MD, and Bradley Monk, MD
View the expert analysis with Bradley Monk, MD, and Michael Birrer, MD, PhD
View eNewsflash
Clinical Care Options Oncology - Ovarian Cancer
Note: registration is required/ free
Ovarian Cancer Source: CCO Independent Conference Coverage of the CCO Independent Conference Coverage of the 2010 American Society of Clinical Oncology Annual Meeting*
Expert Analysis: Ovarian Cancer (coming soon)
Faculty:
* Thomas J. Herzog, MD
* Bradley J. Monk, MD, FACOG, FACS
Capsule Summaries
* Randomized, Double-Blind, Placebo-Controlled Phase II Study of AMG 386 Combined With Weekly Paclitaxel in Patients (pts) With Recurrent Ovarian Carcinoma (coming soon)
* Efficacy and Safety of Farletuzumab, a Humanized Monoclonal Antibody to Folate Receptor alpha, in Platinum-Sensitive Relapsed Ovarian Cancer Subjects: Final Data From a Multicenter Phase II Study (coming soon)
* A Phase II Study of Bevacizumab With Nab-Paclitaxel in Patients With Recurrent, Platinum-Resistant Primary Epithelial Ovarian or Primary Peritoneal Carcinoma (coming soon)
* Phase II Study of NKTR-102 in Women With Platinum-Resistant/Refractory Ovarian Cancer (coming soon)
* Phase III Trial of Bevacizumab (BEV) in the Primary Treatment of Advanced Epithelial Ovarian Cancer (EOC), Primary Peritoneal Cancer (PPC), or Fallopian Tube Cancer (FTC): A Gynecologic Oncology Group Study (coming soon)
* Phase III Trial of Induction Gemcitabine (G) or Paclitaxel (T) Plus Carboplatin (C) Followed by Elective T Consolidation in Advanced Ovarian Cancer (OC): Final Safety and Efficacy Report (coming soon)
* Carboplatin (C) Plus Paclitaxel (P) vs Carboplatin Plus Pegylated Liposomal Doxorubicin (PLD) in Patients With Advanced Ovarian Cancer (AOC): Final Analysis of the MITO-2 Randomized Multicenter Trial (coming soon)
Medical News: ondansetron - Cancer Antiemetic Recalled By Drugmaker - in Product Alert, Prescriptions from MedPage Today
Cancer Antiemetic Recalled By Drugmaker
By Cole Petrochko, Staff Writer, MedPage Today
Published: June 07, 2010
The distributor of intravenous ondansetron for use in preventing nausea and vomiting in patients undergoing chemotherapy initiated a voluntary recall due to debris and possible contamination of lots of the product.
Nonsterile bags of the treatment may result in potentially fatal infections, particularly in immunocompromised patients.
Affected lot numbers include A090309 through A090312. The pouches were distributed from August 2009 to May 2010.....
Please sign the Ovarian Cancer Pettion & Circulate widely: U.S. Ovarian Cancer Awareness Postage Stamp
In memory of Carolyn Benivegna, survivors, family and friends of those touched by ovarian cancer, please click on the link and help us send our message through the U. S. Postal Service. http://www.ipetitions.com/petition/ovcastamp
press release: OncoGenex/OGX-427
BOTHELL, WA, and VANCOUVER, June 7 /CNW/ - OncoGenex Pharmaceuticals, Inc. (NASDAQ: OGXI) today announced final results from a Phase 1 trial. The primary purpose of this trial was to evaluate the safety and tolerability of OGX-427 up to doses of 1000 mg for the treatment of various solid tumors. Patients enrolled had a diagnosis of castrate resistant prostate cancer, breast cancer, ovarian cancer or non-small cell lung cancer. Final results showed that OGX-427 was safe and well tolerated as a monotherapy as well as in combination with docetaxel. In addition, OGX-427 when used as a single agent demonstrated declines in circulating tumor cells at all doses and in all diseases evaluated, as well as evidence of reduction in tumor markers in prostate and ovarian cancer. Results were presented today at the 46th Annual Meeting of the American Society of Clinical Oncology (ASCO)...."
GOG 218 Phase III Study Showed Avastin-Based Regimen Helped Women with Advanced Ovarian Cancer Live Longer Without Their Disease Worsening | news
Note: more detailed information in this article
ELC : Detail Imedix (Best of the Day from ASCO) - video June 6th
Note: registration is required to view this video/site (free)
POF (premature ovarian failure) Mount Sinai Hospital - Help for Women with Early Menopause
Note: this does not include surgical menopause
"Other POF patients have survived cancer in their youth, only to learn that they will have to spend their entire life dealing with the ramifications of that early treatment."
Barriers to participation in cancer prevention clinical trials; Acta Oncologica - 0(0):Pages 1-10 - Informa Healthcare
Abstract
Background. Cancer prevention clinical trials seek to enroll individuals at increased risk for cancer. Little is known about attitudes among physicians and at-risk individuals towards cancer prevention clinical trials. We sought to characterize barriers to prevention trial participation among medical oncologists and first-degree relatives of their patients.
Methods. Physician participants were practicing oncologists in Pennsylvania. Eligible first-degree participants were adult relatives of a cancer patient being treated by one of the study physicians. The influence of perceived psychosocial and practical barriers on level of willingness to participate in cancer prevention clinical trials was investigated.
Results. Response rate was low among physicians, 137/478 (29%), and modest among eligible first-degree relatives, 82/129 (64%). Lack of access to an eligible population for prevention clinical trials was the most commonly cited barrier to prevention clinical trials among oncologists. Nearly half (45%) of first-degree relatives had not heard of cancer prevention clinical trials, but 68% expressed interest in learning more, and 55% expressed willingness to participate. In the proportional odds model, greater information source seeking/responsiveness (i.e., interest in learning more about clinical prevention trials from more information sources) (p = 0.04), and having fewer psychosocial barriers (p = 0.02) were associated with a greater willingness to participate.
Conclusions. Many individuals who may be at greater risk for developing cancer because of having a first-degree relative with cancer are unaware of the availability of clinical cancer prevention trials. Nonetheless, many perceive low personal risk associated with these studies, and are interested in learning more.
What Happened at ASCO Over the Weekend - Health Blog - WSJ
"There was also news from Roche about another often-deadly form of cancer (ovarian cancer). Continuing the use of Avastin for two years following a chemo/Avastin regimen gave ovarian cancer patients an additional four months of progression-free survival, to 14 months total. Long-term use of Avastin is a pricey proposition, however, given its cost of up to $56,000 a year. Here’s the WSJ story.
Fox News posts story making preposterous claim about breast cancer - Gary Schwitzer's HealthNewsReview Blog
Note: dissecting media reports
The Health Care Economy: Where the Jobs Are - TheFiscalTimes.com
Blogger's Note: the financial health of the healthcare industries (global) is very much in discussion. This website has numerous articles for discussion on topics such as below. After a cursory look, it seems charities have not been touched which may be a cause for concern for many given the time of year when many charities focus on their events. In one recent example in Toronto, the head of the hospital charity/fundraising conglomerate earned more than the head of the actual hospital itself. Whether it is a charity or whether it is the hospital/insurance/system itself, the question begs consideration of all factors - where is the money going?
Life at all Costs: The Politics
Life at All Costs: Dying Abroad
Life at All Costs: The Solutions
Life at All Costs: The Choices
Life at All costs: The Mid-Death Crisis
Justice Holmes Had it Right on Taxes
Social Security: Getting Facts Right
The Evil of Taxation
Sunday, June 06, 2010
ASCO: Striking the Balance: Community Experts Come Together for High-Level Dialogue on Cancer Care - MarketWatch
More information about Breakaway from Cancer, including valuable resources offered by Amgen's partners, is available at www.breakawayfromcancer.com.
IPSOS poll and Canadians' view on healthcare + online debate June 6th
The sold out debate will be broadcast for free on the internet at http://www.munkdebates.com starting a 7:00 PM EDT.
Saturday, June 05, 2010
Friday, June 04, 2010
Cancer genetics and reproduction
Abstract
Cancers of the reproductive organs (i.e., ovaries, uterus and testes), like other cancers, occur as a result of a multi-stage interaction of genetic and environmental factors. A small proportion of cancers of the reproductive organs occur as part of a recognised cancer syndrome, as a result of inheritance of mutations in highly penetrant cancer susceptibility genes (e.g., BRCA1, BRCA2, MLH1 or MSH2). Recognition of individuals and families with inherited cancer predisposition syndromes and individuals at high risk due to familial cancer clustering is fundamentally important for the management and treatment of the current cancer and for future prevention of further cancers for the individual and their extended family
'The worst thing about hospice is that they talk about death': contrasting hospice decisions and experience among immigrant Central and South American Latinos with US-born White, non-Latino cancer caregivers
Abstract:
Hospice care is promoted as a model for improving end of life care and decreasing burden on caregivers. However, hospice use is low in Latinos and little is known about how Latinos make hospice decisions and experience hospice once enrolled. Qualitative methods were used in this study to conduct in-depth interviews and focus groups with 15 Latino bereaved hospice family caregivers and 15 White non-Latino bereaved hospice family caregivers to describe hospice experiences and evaluate whether cultural factors affected the experience. Differences in decision-making and caregiving experience were identified that were influenced by culture. For example, cultural values of denial, secrecy about prognosis and a collective, family-centered system influenced hospice decisions and experience in Latinos but not non-Latinos. This study identifies a significant dilemma: that is, how to discuss hospice with a patient and family who prefer not to discuss a terminal prognosis. Future research is needed to extend these preliminary results; such results may be useful for designing interventions to improve end of life care and caregiving in Latinos.
'They've got to learn' -- a qualitative study exploring the views of patients and staff regarding medical student teaching in a hospice
Abstract:
UK medical school curricula incorporate training in end-of-life care as recommended by Tomorrow’s Doctors.
Previous research suggests that hospice staff have concerns about the burden on patients when participating in medical student teaching and may gatekeep access to patients.
This qualitative study uses semistructured interviews to explore and compare the views of hospice patients and health care staff about patient involvement in medical student teaching. Fifteen patients and 14 staff members were recruited from a single UK hospice involved in teaching third year medical students.
Hospice patients, who have been involved in teaching, are strongly positive about meeting medical students and staff carefully select patients based on a number of issues.
Abstract/full free access: The distribution of the therapeutic monoclonal antibodies cetuximab and trastuzumab within solid tumors
In research/technical:
Conclusions
Cetuximab (Erbitux) and trastuzumab (Herceptin) distribute slowly, but at higher doses achieve a relatively uniform distribution after about 24 hours, most likely due to their long half-lives in the circulation. There remains poor distribution within hypoxic (hypoxia - a deficiency of oxygen reaching the tissues of the body) regions of tumors.
Thursday, June 03, 2010
It's a choice to move forward: women's perceptions about treatment decision making in recurrent ovarian cancer
Abstract
OBJECTIVE: This research explores the treatment decision-making (TDM) experiences of women with recurrent ovarian cancer (ROC) with regard to treatment options; their understanding of risks and benefits of various treatment options; the decision-making role they want for themselves and for their oncologist; and the social context of the consultation as it pertains to the decision.
METHODS: We conducted semi-structured interviews with 26 women at the time of first recurrence. Through inductive data analysis key themes were identified.
RESULTS: Many women describe self-identifying the cancer recurrence fairly quickly due to new symptoms. Many feel that the goal for treating their recurrence is to control versus cure the cancer. They describe the subsequent process of diagnosis and TDM for ROC as quick and straightforward with all women accepting the oncologists' treatment recommendation. They feel that the type and number of treatment options are limited. They have a strong desire for physician continuity in their care. Participants feel that their doctor's recommendations as well as their previous experience with ovarian cancer are strong factors influencing their current TDM process.
CONCLUSIONS: Shared decision making is based on a simultaneous participation of both the physician and patient in TDM. When faced with ROC, women feel that their doctor's recommendation and their past experience with treatment and TDM are prominent factors influencing the current TDM process.
Trabectedin Plus Pegylated Liposomal Doxorubicin in Recurrent Ovarian Cancer. (multinational study)
Note: Trabectedin is also known as Yondelis PURPOSE The objective of this study was to compare the efficacy and safety of trabectedin plus pegylated liposomal doxorubicin (PLD) with that of PLD alone in women with recurrent ovarian cancer after failure of first-line, platinum-based chemotherapy CONCLUSION When combined with PLD, trabectedin improves PFS and ORR over PLD alone with acceptable tolerance in the second-line treatment of recurrent ovarian cancer.
Comprehensive Analysis of Missense Variations in the BRCT Domain of BRCA 1 by Structural and Functional Assays
Comprehensive Analysis of Missense Variations in the BRCT Domain of BRCA1 by Structural and Functional Assays.
Lee MS, Green R, Marsillac SM, Coquelle N, Williams RS, Yeung T, Foo D, Hau DD, Hui B, Monteiro AN, Glover JN.
Authors' Affiliations: Department of Biochemistry, School of Systems Molecular Medicine, University of Alberta, Edmonton, Alberta, Canada; National Institute of Environmental Health Sciences, Durham, North Carolina; Risk Assessment, Detection, and Intervention Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida; and Molecular Biology Program, Institute of Biophysics Carlos Chagas Fo., Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Abstract
Genetic screening of the breast and ovarian cancer susceptibility gene BRCA1 has uncovered a large number of variants of uncertain clinical significance. Here, we use biochemical and cell-based transcriptional assays to assess the structural and functional defects associated with a large set of 117 distinct BRCA1 missense variants within the essential BRCT domain of the BRCA1 protein that have been documented in individuals with a family history of breast or ovarian cancer....... Through a correlation of the assay results with available family history and clinical data, we define limits to predict the disease risk associated with each variant. Forty-two of the variants show little effect on function and are likely to represent variants with little or no clinical significance; 50 display a clear functional effect and are likely to represent pathogenic variants; and the remaining 25 variants display intermediate activities. The excellent agreement between the structure/function effects of these mutations and available clinical data supports the notion that functional and structure information can be useful in the development of models to assess cancer risk.
2nd media article: HE4: Abbott gets FDA approval for ovarian cancer test - Chicago Breaking Business
"Abbott partnered with Fujirebio Diagnostics Inc. to develop the test. It also is approved for use in Europe, and other countries in the Asia Pacific and Latin American regions."
support group meetings - feel free to share - OCATS June 7th
OCATS Ovarian Cancer Awareness & Treatment in Saskatchewan ------------------------------------------------------------------------------------- GYNECOLOGIC CANCER SURVIVORS & SUPPORT PEOPLE WELCOME MONDAY, June 7th 4:00 p.m. to 6:00 p.m. Knox Met United Church 2340 Victoria Avenue (Pls Use Vic Ave Entrance, Ring Buzzer for Room 105) Light Supper, $4 Donation This month our peer support gathering will have our regular check in, and then a facilitated discussion about the challenges and coping strategies for socializing and traveling after diagnosis, while having treatment, during recovery. We don’t have the answers exactly but we’ll share some of the experiences we’ve had for air travel, car travel, hotels, family holidays, special events and share how people have coped and what things they found were useful and helpful or things to avoid. Please come share in the discussion, meet other cancer survivors. It’s good to get out once in awhile and share with others, learn from others. It’s even okay to be grumpy about it! If that’s where you’re at. Please call Darlene at 775-1848 or email and let us know if you plan to attend. This helps Joan prepare those lovely meals she making for us! Thank you, Darlene Gray OCATS Ovarian Cancer Awareness & Treatment in Saskatchewan A SUPPORT & ACTION GROUP FOR ANYONE AFFECTED BY GYNECOLOGIC CANCERS RPO Box 35067, Regina, SK S4X 4C6 Ph 306-775-1848, Fx 306-775-1853 Find us on Facebook too! http://www.ocats.ca
Study Testing Methylphenidate for Cancer-Related Fatigue Indicate That It Is Certainly Not a Panacea but May Be Effective for Some Groups of Patients
VIDEO ALERT: Additional audio and video resources, including excerpts from an interview with Dr. Deb Barton is available on the http://newsblog.mayoclinic.org/2010/06/02/mayo-clinic-study-shows-drug-may-be-effective-in-treating-cancer-related-fatigue-in-some-patients/ Mayo Clinic News Blog.
The BRCA1 c.5434C→G (p.Pro1812Ala) variant induces a deleterious exon 23 skipping by affecting exonic splicing regulatory elements -- Gaildrat et al. 47 (6): 398 -- Journal of Medical Genetics
Blogger's Note: in plain english - many patients who have undergone genetic testing show test results of 'unknown variants' or variants of unknown clinical significance but negative for known mutations ie; BRCA 1/2; MSH2/6; MLH1; PMS2.
Some of these unclassified variants may or may not be related to cancer. With recent research, databases are now showing UV (unclassified variants) as true mutations.
This article is one of many which shows the work being done to explain and find the significance of these variants. Many patients undergoing genetic testing will test negative for the commonly known mutations, but this is not the'end of the story', so to speak.
Conclusion These data, together with segregation data, argue for the classification of BRCA1 c.5434C→G as a pathogenic splicing mutation. These results also suggest that UVs (unclassified variants)in highly conserved nucleotide sequences of short exons may be good candidates for detecting functionally relevant splicing regulatory elements.
New blood thinners can cause dangerous drug interactions, study finds
""A high proportion of adults in the United States consume at least one of the drugs known to have some level of interaction with one of the new oral anticoagulants," the Loyola researchers write."
Stem cell researchers uncover previously unknown patterns in DNA methylation
"The findings could have implications in fighting cancer because DNA methylation patterns go awry in cancer, often causing tumor suppressor genes to switch off. The more scientists know about the cellular mechanisms that lay down the correct DNA methylation patterns, the more that process can be manipulated. In the future, this type of research may lead to techniques that result in the ability to control the patterns that go awry and lead to cancer, thus preventing a malignancy"
Wednesday, June 02, 2010
Chronix Biomedical to Launch Cancer Detection and Monitoring Service at ASCO to Advance Clinical Research Using Its Apoptotic DNA Blood Test | Business Wire
Note: in research "Chronix Biomedical to Launch Cancer Detection and Monitoring Service at ASCO to Advance Clinical Research Using Its Apoptotic DNA Blood Test —ASCO Data Show Chronix’s Apoptotic DNA Blood Test Detects Early-Stage Cancer with Excellent Sensitivity and Specificity— —“For Investigational Use Only” Clinical Trial Service Is Designed to Provide Early Data on Patient Response and Disease Progression"
Functional Proteomic Analysis of Advanced Serous Ovarian Cancer Using Reverse Phase Protein Array: TGF-β Pathway Signaling Indicates Response to Primary chemotherapy
Abstract Purpose: Using reverse phase protein array, we measured protein expression associated with response to primary chemotherapy in patients with advanced-stage, high-grade serous ovarian cancer. Conclusion: TGF-β pathway signaling likely plays an important role as a marker or mediator of chemoresistance in advanced serous ovarian cancer. On this basis, future studies to develop and validate a useful predictor of treatment failure are warranted.
A genomic and transcriptomic approach for a differential diagnosis between primary and secondary ovarian carcinomas in patients with a previous histor
CONCLUSIONS: In patients with ovarian carcinoma and a previous history of breast cancer, SNP array analysis can be used to distinguish primary and secondary ovarian tumors.
Diagnosis of Ovarian Carcinoma Cell Type is Highly Reproducible: A Transcanadian Study
Abstract:
Reproducible diagnosis of ovarian carcinoma cell types is critical for cell type-specific treatment. The purpose of this study was to test the reproducibility of cell type diagnosis across Canada. Analysis of the interobserver reproducibility of histologic tumor type was performed among 6 pathologists after brief training in the use of modified World Health Organization criteria to classify ovarian carcinomas into 1 of 6 categories: high-grade serous, endometrioid, clear cell, mucinous, low-grade serous, and other. These 6 pathologists independently reviewed a test set of 40 ovarian carcinomas. A validation set of 88 consecutive ovarian carcinomas drawn from 5 centers was subject to local review by 1 of the 6 study pathologists, and central review by a single observer. Interobserver agreement was assessed through calculation of concordance and kappa values for pair-wise comparison. For the test set, the paired concordance between pathologists in cell type diagnosis ranged from 85.0% to 97.5% (average 92.3%), and the kappa values were 0.80 to 0.97 (average 0.89). Inclusion of immunostaining results did not significantly improve reproducibility (P=0.69). For the validation set, the concordance between original diagnosis and local review was 84% and between local review and central review was 94%. The kappa values were 0.73 and 0.89, respectively. With a brief training exercise and the use of defined criteria for ovarian carcinoma subtyping, there is excellent interobserver reproducibility in diagnosis of cell type. This has implications for clinical trials of subtype-specific ovarian carcinoma treatments.
Abstract/full free access: Legislation for trial registration and data transparency
"Public confidence in clinical trials has been eroded by data suppression, misrepresentation and manipulation. Although various attempts have been made to achieve universal trial registration- e.g., Declaration of Helsinki, WHO clinical Trial Registry Platform (WHO ICTRP), the International Committee of Medical Journal Editors requirement- they have not succeeded, probably because they lack the enough power of enforcement. Legislation appears to be the most efficient and effective means to ensure that all researchers register their trials and disseminate their data accurately and in a timely manner. We propose that a global network be established. This could be accomplished in two steps. The first step is to legislate about trial registration and data transparency, such as USA's FDAAA Act 2007; and the second step to establish a global network to ensure uniform, international consistency in policy and enforcement of trial registration and data transparency."
focus on: Cancer Neuropathic Pain: Overview of Current Status and Future Objectives -- The Oncologist
ARTICLES
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Cancer Neuropathic Pain: Overview of Current Status and Future Objectives
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Frederick H. Hausheer, Kathleen M. Foley
The Oncologist 2010; 15(Supplement 2): 1-2; doi:10.1634/theoncologist.2009-S506[Full Text] [PDF]
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Mark J. Lema, Kathleen M. Foley, Frederick H. Hausheer
The Oncologist 2010; 15(Supplement 2): 3-8; doi:10.1634/theoncologist.2009-S505[Abstract] [Full Text] [PDF] SUMMARY: This article briefly surveys the types and causes of neuropathic pain and then discusses what is known about the epidemiology of cancer-related neuropathic pain.
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Gary J. Bennett
The Oncologist 2010; 15(Supplement 2): 9-12; doi:10.1634/theoncologist.2009-S503[Abstract] [Full Text] [PDF] SUMMARY: The article reviews some of the work that has been done to study the peripheral causes of neuropathic pain as it relates to cancer.
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Charles S. Cleeland, John T. Farrar, Frederick H. Hausheer
The Oncologist 2010; 15(Supplement 2): 13-18; doi:10.1634/theoncologist.2009-S501[Abstract] [Full Text] [PDF] SUMMARY: This article briefly outlines the currently accepted measures of neuropathy and neuropathic pain, discusses their commonalities and limitations, and offers thoughts on improvements to current assessment strategies.
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Barrie R. Cassileth, Francis J. Keefe
The Oncologist 2010; 15(Supplement 2): 19-23; doi:10.1634/theoncologist.2009-S504[Abstract] [Full Text] [PDF] SUMMARY: This article briefly describes research illustrating the promise of important integrative oncology therapies for the treatment of cancer-related neuropathic pain, including massage therapy, acupuncture, and psychological/behavioral interventions.
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Miroslav Backonja, Clifford J. Woolf
The Oncologist 2010; 15(Supplement 2): 24-29; doi:10.1634/theoncologist.2009-S502[Abstract] [Full Text] [PDF] SUMMARY: This article briefly reviews emerging treatments for neuropathic pain and discusses specific opportunities to alter the drug discovery paradigm, stressing the need for an approach that emphasizes the unbiased evaluation of the particular neurobiological mechanisms contributing to neuropathic pain in individual patients.
Tuesday, June 01, 2010
Welcome to Cancereducation.com
"The landscape of oncolgy continues to evolve as the results from studies are evaluated. All of us at http://www.cancereducation.com are pleased to provide coverage of these critical issues in oncology through our attendance at the 46th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, IL, from June 4–8.
With over 30,000 oncology professionals gathering to discuss the latest innovations in research, quality of life issues, practice, and technology in the oncology community, our staff will attend several of the education and scientific sessions at ASCO.
Their daily updates will be posted on our blog* which can be accessed by clicking on the link at the top of the http://www.cancereducation.com home page."
Marshall Edwards Announces Final Results From Halted Phase 3 Clinical Trial of Phenoxodiol - MarketWatch
Note: these results have been awaited since late last year as per past blogged postings (pending compilation of data)
press release
June 1, 2010, 8:31 a.m. EDT · Recommend · Post:
Marshall Edwards Announces Final Results From Halted Phase 3 Clinical Trial of Phenoxodiol
SYDNEY, AUSTRALIA and SAN DIEGO, CA, Jun 01, 2010 (MARKETWIRE via COMTEX) -- Marshall Edwards, Inc., an oncology company focused on the clinical development of novel anti-cancer therapeutics, announced today that a final analysis of its Phase 3 OVATURE trial of orally administered phenoxodiol in women with recurrent ovarian cancer determined that the trial did not show a statistically significant improvement in its primary (progression-free survival) or secondary (overall survival) endpoints. As previously announced, the trial was closed for recruitment before completion of enrolment with only 142 out of a planned 340 patients enrolled.
This multi-center, randomized, double-blind trial assessed the safety and efficacy of daily phenoxodiol in combination with weekly carboplatin versus weekly carboplatin with placebo in patients with platinum-resistant or platinum-refractory, late-stage epithelial ovarian, fallopian or primary peritoneal cancer following at least second line platinum therapy.
"Owing to the fact that this trial was significantly underpowered due to the small number of patients enrolled, we were disappointed, but not entirely surprised by the final outcome," said Dr. Daniel P. Gold, newly appointed Chief Executive Officer of Marshall Edwards. "However, we remain confident that our investigational isoflavone platform, including triphendiol, a potentially more potent, second-generation analogue of phenoxodiol, may be of benefit to women with ovarian cancer, particularly when administered intravenously.
"Previously reported results of a Phase 2 trial," continued Dr. Gold, "which tested the activity of intravenous phenoxodiol plus weekly cisplatin in a similar platinum-resistant or refractory patient population, demonstrated a 30% response rate (6 out of 20) compared to less than 1% (1 out of 142) in the OVATURE study in which phenoxodiol was administered orally. In addition, we remain excited with the progress of another product candidate in our pipeline, NV-128, a novel isoflavone analogue with a mode of action distinct from both phenoxodiol and triphendiol.
"Lastly, I want to take this opportunity to personally thank the patients and their families for their participation in this trial. I would also like to thank the clinical investigators and trial coordinators for their dedication and support."
Safety Outcomes
As previously noted, phenoxodiol had a good safety profile and was well tolerated. The number of patients experiencing at least one adverse event was similar in each treatment group, as was the number of patients experiencing adverse events of Grade 3 or higher.
About OVATURE and the Phenoxodiol Clinical Program
The OVATURE ("OVArian TUmor REsponse") trial was a multi-center international Phase 3 clinical trial of orally administered investigational drug phenoxodiol in combination with carboplatin in women with advanced ovarian cancer resistant or refractory to platinum-based drugs to determine its safety and effectiveness when used in combination with carboplatin.
The trial recruited ovarian cancer patients whose cancer initially responded to chemotherapy, but had since become resistant or refractory to traditional platinum treatments. The study was closed to enrolment in April 2009 at which time 142 patients had been randomized to the study. Changes in standards of care over the period of the trial and the stringency of inclusion/exclusion criteria of the OVATURE protocol had slowed patient recruitment rates and consequently the Company deemed it prudent not to continue the trial to completion. The Independent Data Monitoring Committee (IDMC) supported the Company's decision to close the study to accrual, and, in a review of the available safety data, the IDMC confirmed that there were no safety concerns with phenoxodiol in these subjects.
About Phenoxodiol
Phenoxodiol is being developed as a chemosensitizing agent in combination with platinum drugs for late stage, chemoresistant ovarian cancer and as a monotherapy for prostate and cervical cancers. It is believed to have a unique mechanism of action, binding to cancer cells via a cell membrane oxidase, causing major downstream disturbances in expression of proteins necessary for cancer cell survival and responsible for the development of drug resistance.
Phenoxodiol appears to selectively inhibit the regulator known as S-1-P (sphingosine-1-phosphate) that is overexpressed in cancer cells. In response to phenoxodiol, S-1-P content is decreased, with a consequent decrease in expression of the pro-survival proteins XIAP and FLIP, inducing cell death via caspase expression and promoting sensitivity to other chemotherapeutics. In laboratory studies, it has been demonstrated that drug-resistant ovarian cancer cells pre-treated with phenoxodiol were killed with lower doses of chemotherapy drugs. Importantly, phenoxodiol has been shown not to adversely affect normal cells in animal and laboratory testing.
Phenoxodiol has been granted Fast Track status from the FDA to facilitate its development as a therapy for recurrent ovarian and prostate cancers. Fast Track designation is designed to facilitate the review of products that address serious or potentially life-threatening conditions for which there is an unmet medical need and provides the option to file a New Drug Application on a rolling basis. This permits the FDA to review the filing as it is received, expediting the review process. Phenoxodiol is an investigational drug and, as such, is not commercially available. Under U.S. law, a new drug cannot be marketed until it has been investigated in clinical trials and approved by FDA as being safe and effective for the intended use.
Memorandum to Shareholders From Dr. Amnon Gonenne, MabCure's Chief Executive Officer - MarketWatch
June 1, 2010, 8:00 a.m. EDT · Recommend · Post:
Memorandum to Shareholders From Dr. Amnon Gonenne, MabCure's Chief Executive Officer
HASSELT, Belgium, Jun 01, 2010 (BUSINESS WIRE) -- MabCure, Inc. /quotes/comstock/11k!mbci (MBCI 0.32, -0.01, -3.03%) :
Dear Shareholders:
I am pleased to update you on the progress of our research and development.
Over the past several months we have been working intensively on advancing our various programs with an emphasis on melanoma and ovarian cancer diagnostics. We consider these two projects near-term in their respective development stages, as I describe below.
In January 2010, we announced the commencement of our clinical trials at the Ramathibodi Hospital in Bangkok, Thailand to evaluate the potential of our panel of monoclonal antibodies (MAbs) to diagnose ovarian cancer in high risk patients. Since the study began, patients have been recruited at a solid pace and in line with our schedule. In addition, we are privileged that the Thai National Cancer Institute has decided to join our study and is currently reviewing our study protocol. The study is estimated to be completed within 5-6 months, as originally planned.
In parallel to our study in Thailand, we are planning to commence a study in collaboration with a major medical center in Belgium of several hundred blood samples which were obtained from patients over the past several years. The purpose of this "retrospective" study is to provide additional proof of the ability of our MAbs to correctly diagnose ovarian cancer, and is of considerable importance given the significant number of blood samples to be tested.
The study will be "blind" to all involved (i.e. the samples will be coded and neither the clinicians nor MabCure scientists will know the identity of the specimens until the study is complete), so as to prevent any bias in the analysis of the results. The study is expected to last several weeks and will commence once a formal agreement has been signed with the Belgian medical center. As a prelude to this study, we conducted a pilot study on a limited number of these "retrospective" specimens to calibrate the optimal technical conditions for our MAbs.
Activism among exceptional patients with cancer. [Support Care Cancer. 2010] - PubMed result
Abstract
BACKGROUND: The "exceptional patients" with cancer are survivors who had advanced cancer considered incurable by medical report and who subsequently became disease-free or experienced unexplained survival time given the nature of their disease or treatment. This experience is a puzzling phenomenon that has not been formally investigated in a cancer population. The purpose of this study was to understand exceptional patients' accounts of their experience.
MATERIALS AND METHODS: This study used a narrative approach with a cross-case thematic analysis. Recruitment took place at health care centers in the USA and Israel. Oncologists in both centers were asked to identify patients who had an exceptional disease course. Patients were then contacted and interviewed; an audio recording was made of each narrative account and then transcribed. Interviews and thematic analyses were conducted independently at each site. These thematic findings from each site were discussed with both research teams and a common underlying theme was identified, which is the focus of this report.
RESULTS: Twenty-six participants were interviewed: 14 from the USA and 12 from Israel. All the participants have had advanced disease with a range of diagnoses that included breast, colorectal, pancreatic, ovarian cancer, glioblastoma multiforme, and others. The main recurrent theme from both the US and Israeli sites was personal activism. This was manifested in taking charge and getting involved in the process of diagnosis and treatment, as well as becoming more altruistic in their relationships with others. In many cases, this was reflected in a change in a philosophy about life
CONCLUSIONS: In this study, we found that activism was a major theme that was independently observed in both Israel and the USA. This has implications for health care providers to facilitate patient engagement in the care and treatment of their disease. Further research on this phenomenon is needed.
Medical News: Hand Hygiene in Hospitals Not Up to Par - in Infectious Disease, Infection Control from MedPage Today
Each year, an estimated 2.5 million patients in the U.S. develop healthcare-associated infections that result in 90,000 deaths and cost the healthcare system an estimated $4.5 to $5.7 billion dollars
Anti-MUC1 Antibodies and Ovarian Cancer Risk: Prospective Data from the Nurses' Health Studies — Cancer Epidemiology, Biomarkers & Prevention
Note: MUC1 has been/is being studied in numerous cancers
Conclusion: Anti-MUC1 (glycoprotein) antibodies evaluated several years before diagnosis may be associated with lower risk of subsequent ovarian cancer in women <64 years old at assessment.
May 20th, 2010 SGO statement - (U.S.) statement - House Defense Appropriations Subcomittee
Note: clicking above uploads directly the pdf file version
Statement of Daniel L. Clarke-Pearson, M.D. President - Society of Gynecologic Oncologists Professor and Chair, Obstetrics and Gynecology University of North Carolina Medical School Chapel Hill, North Carolina On Behalf of The Society of Gynecologic Oncologists Before The House Defense Appropriations Subcommittee
Thursday, May 20, 2010 at 10:00 am
SGO E-Learning Center
SGO's 41st Annual Meeting on Women's Cancer Webcast Available Now!
FREE Introduction to Presidential Address, Cornelius Granai, MD
FREE Presidential Address, David Mutch, MD
FREE ACS Lectureship, Paul Goodfellow, PhD
Monday, May 31, 2010
Survivorship in Lynch Syndrome Families - Full Text View - Clinical Trial
Further study details as provided by M.D. Anderson
Cancer Center:
Primary Outcome Measures: Compare Predictors of Health-Related Quality of Life (QOL) among Colorectal Cancer (CRC) Survivors who have Lynch Syndrome (LS) with patients who have Sporadic CRC [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
Simulation in Surgery: Perfecting the Practice
abstract
The apprenticeship model that surgical training has traditionally relied on has proven to be an expensive, time-consuming, and inconsistent model for producing skilled surgeons. Combined with increased public scrutiny on patient safety, financial concerns, restricted work hours, and expanding skill requirements, it has become clear that a new pedagogic paradigm is required. This article reviews the evidence supporting the need and justification of simulation in surgical education and explores the existing and potential roles of simulation in the training and evaluation of future surgeons.
LISTSERV Choice Awards: vote for your favourite listserv (ACOR/Ovarian Cancer results to date)
Should Cause of Death From the Death Certificate Be Used to Examine Cancer-Specific Survival? A Study of Patients With Distant Stage Disease; Cancer Investigation
ABSTRACT
Death certificates are used to classify cause of death for studies of cancer survival and mortality. Using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program, we evaluated cause of death (site-specific, cancer cause-specific, or other cause of death) for 229,181 patients with distant stage disease during 1994–2003 who died by 2005. Agreement between coded cause of death and initial diagnosis was 85% in patients with only one primary and 64% in patients with more than one primary. Our findings support the usefulness of site and cancer cause-specific causes of death reported on the death certificate for distant stage patients with a single cancer.
abstract/free full pdf access:P redictive and Prognostic Protein Biomarkers in Epithelial Ovarian Cancer: Recommendation for Future Studies Cancers
"Abstract: Epithelial ovarian cancer is the most lethal gynecological malignancy. Due to its lack of symptoms, this disease is diagnosed at an advanced stage when the cancer has already spread to secondary sites. While initial rates of response to first treatment is >80%, the overall survival rate of patients is extremely low, mainly due to development of drug resistance. To date, there are no reliable clinical factors that can properly stratify patients for suitable chemotherapy strategies. Clinical parameters such as disease stage, tumor grade and residual disease, although helpful in the management of patients after their initial surgery to establish the first line of treatment, are not efficient enough. Accordingly, reliable markers that are independent and complementary to clinical parameters are needed for a better management of these patients. For several years, efforts to identify prognostic factors have focused on molecular markers, with a large number having been investigated. This review aims to present a summary of the recent advances in the identification of molecular biomarkers in ovarian cancer patient tissues, as well as an overview of the need and importance of molecular markers for personalized medicine in ovarian cancer."
..........
"High grade serous tumors show particular differences in terms of their development, genetic alterations and prognosis. This has led to the classification of ovarian cancer into two types: type 1 tumors, which are low grade and slowly developing (endometrioid, mucinous and low grade serous tumors), and type 2 tumors, which rapidly progress (high grade serous). In addition, the association of biomarker expression with survival varies substantially between subtypes, and can easily be overlooked in whole cohort analyses. Although these data suggest substantial differences between subtypes, until recently ovarian carcinomas were typically approached as a monolithic entity by researchers and clinicians. This practice impeded progress in understanding the biology or improving the management of the less common ovarian carcinoma subtypes. To avoid this effect, each subtype within a cohort should be analyzed individually. Therefore, molecular classifiers of ovarian cancer are of high clinical relevance in the management of these cancer patients...." cont'd
Fertility Success: Researchers Determine How Chemo Affects Female Fertility
"Chemotherapy induces menopause in some hormone-dependent cancers. It has a beneficial effect because it's withdrawing the stimulants for the cancer cells. Menopause is contributing to the cure," said Astsaturov. "It's still debated whether we should preserve menstrual function at all costs."
Emerging drugs for ovarian cancer
"Strategies currently being exploited in clinical trials include attempts to deliver more killing selectively to tumours (e.g., intraperitoneal administration of cisplatin or radiolabelled monoclonal antibodies), agents designed to target drug resistance mechanisms (e.g., TLK-286 activated by glutathione transferase), agents targeting proteins/receptors shown to be selectively expressed in the disease (e.g., monoclonal antibodies recognising CA-125 or HER1; small molecules targeting HER1 such as gefitinib) and disrupting established tumour vasculature (e.g., 5,6-dimethyl xanthenone 4-acetic acid). At the pre-clinical level, agents being developed to target the phosphatidylinositol 3 kinase/AKT/mTOR pathway, and K-Ras inhibitors, may offer efficacy in the future."
Saturday, May 29, 2010
Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts
BACKGROUND:
Genetic screening of breast cancer patients and their families have identified a number of variants of unknown clinical significance in the breast cancer susceptibility genes, BRCA1 and BRCA2.
CONCLUSIONS:
These results illustrate the need for improved methods for predicting functional ESEs and the potential consequences of sequence variants contained therein.
Patient navigation in breast cancer: a systematic review
Note: the abstract does not provide a definition of 'patient navigator'
IMPLICATIONS FOR PRACTICE: Data describing the role of patient navigation in breast cancer will assist in better defining future direction for the breast navigation role. Ongoing research will better inform issues related to role definition, integration into clinical breast cancer care, impact on quality of life, cost-effectiveness, and sustainability.
Thursday, May 27, 2010
abstract/full free access; pilot study assessing social support among cancer patients enrolled
Conclusions: Younger subjects reported worse symptoms, a smaller social support network, and fewer close friends and relatives than older subjects. Having someone to discuss decisions and seeing friends or relatives often was associated with longer survival.
Peri- and post-menopausal incidental adnexal masses and the risk of sporadic ovarian malignancy: new insights and clinical management.
Abstract
Adnexal masses are common among peri- and post-menopausal women. Although ovarian cancer is a significant cause of mortality in menopausal women, large population-based studies demonstrate that the majority of adnexal masses are benign. Despite this, the appearance of an adnexal mass is a concern for the patient and an insight exercise for physicians. In most cases, an adnexal enlargement is an incidental finding, generally corresponding to a benign cyst and easily diagnosed by conventional ultrasound. Exceptionally an ovarian tumour may be malignant and should be treated as early as possible. When conventional ultrasound renders complex morphology other diagnostic tools must be used such as: colour Doppler and functional tumour vessel properties, serum CA 125 levels, nuclear magnetic resonance imaging and in some cases laparoscopy. Several new tumour markers are being studied for clinical application, although there are presently no clear recommendations. Adnexal masses with benign morphological and functional properties must be periodically monitored as an alternative to surgery since malignant transformation is exceptional.
Abstract / full free text: Expression signatures of TP53 mutations in serous ovarian cancers
Conclusions This represents the first attempt to define a genomic signature of TP53 mutation in ovarian cancer. Patterns of gene expression characteristic of TP53 mutation could be discerned and included several genes that are known p53 targets or have been described in the context of expression signatures of TP53 mutation in breast cancer.
DiaTech Oncology MiCK Chemotherapy Induced Apoptosis Assay Shows Increased Response and Survival in... -- NASHVILLE, Tenn., May 26 /PRNewswire/ --
Findings Published at the ASCO Conference Provide a New Treatment Strategy for Patients and Support Favorable Reimbursement Coverage Policies
NASHVILLE, Tenn., May 26 /PRNewswire/ -- DiaTech Oncology announced today that the American Society of Cancer Oncology (ASCO) has published the results of a comprehensive study to determine the effectiveness of the Microculture Kinetic (MiCK) assay for apoptosis in predicting increased response and survival rates for ovarian cancer patients. In the MiCK assay, the tumor cells of an individual patient are exposed to multiple doses of several chemotherapeutic drugs either as single drugs or in combinations. A sophisticated algorithm is used to monitor and compute the amounts of apoptosis caused by each of the drugs to establish a drug sensitivity profile of the patient's tumor cells. Knowledge of a patient's drug sensitivity profile allows the treating oncologists to prescribe chemotherapy that would be the most effective against the tumor cells of that patient.
The results showed overall survival significantly better in 92% of patients who received the best chemotherapy as predicted by the MiCK assay compared to only 76% of patients who received treatment not recommended by the assay. There was also a significantly higher overall response rate (82% vs. 54%) for patients who received a treatment the assay showed would be preferred. Ovarian cancer patients in stage 3 or 4 and treated with a highly active assay score had significantly increased survival rates (94% vs. 77% alive at 24 months). The clinical benefit rate was 85% for patients with chemotherapy that was highly active in the assay, compared to only 57% for those patients receiving less active chemotherapy.....
Wednesday, May 26, 2010
Health Canada Approves Trabectedin for Relapsed Ovarian Cancer (Trabectedin//Yondelis)
May 26, 2010 — Health Canada has approved trabectedin (Yondelis; PharmaMar SA [Zeltia SA], marketed by Centocor Ortho Biotech Products, LP) in combination with pegylated liposomal doxorubicin (PLD) for the treatment of relapsed platinum-sensitive ovarian cancer.
The treatment is indicated for patients who have failed (blogger comment - ho hum!) first-line platinum-based chemotherapy regimen, including adjuvant therapy, and who are not expected to benefit from, are ineligible for, or are unwilling to undergo additional platinum-based chemotherapy.
Approval was based on radiologic data from a multinational phase 3 clinical study (n = 672) showing that administration of trabectedin (1.1 mg/m2) plus doxorubicin (30 mg/m2) in 3-week cycles significantly increased progression-free survival by 21% compared with PLD alone (50 mg/m2) given every 4 weeks (7.3 months vs 5.8 months; hazard ratio [HR], 0.79; P = .019).
These findings were confirmed by an independent radiologic assessment that considered clinical as well as radiologic imaging data in assessing tumor progression (HR, 0.72; P = .0008). These study results were presented at the 2008 European Society for Medical Oncology Congress, and reported by Medscape Oncology during the conference.
In July 2009, the FDA declined approval of trabectedin for ovarian cancer, citing the potential for variations in radiologic data assessment and questioning whether the 6-week increase in progression-free survival offset an increased risk for toxicity, as previously reported by Medscape Oncology.
Trabectedin previously was approved in the European Union for the treatment of platinum-sensitive ovarian cancer and soft tissue sarcoma.
abstract: How to follow-up patients with epithelial ovarian cancer.
Abstract
PURPOSE OF REVIEW: Despite optimal primary treatment most patients with advanced epithelial ovarian cancer will relapse. This review discusses the controversy regarding surveillance and the timing of treatment for recurrent disease.
RECENT FINDINGS: Routine physical examination has a limited role in the detection of recurrent ovarian cancer. PET/computed tomography (CT) has been shown to be useful in detecting small volume disease not apparent on traditional imaging in patients with suspected recurrence based on symptoms and/or rising CA125. The results of PET/CT can alter treatment plans and have particular use in guiding site-directed therapy. The benefits of early detection and systemic treatment of recurrence are now in doubt following the presentation of the MRC/EORTC CA125 surveillance trial. The impact on survival of secondary cytoreductive surgery requires more investigation.
SUMMARY: Uncertainties remain in the surveillance and timing of treatment for relapsed disease. Patients should be informed of these uncertainties and become involved in decisions regarding their follow-up.
Tuesday, May 25, 2010
Chemoresponse Assay Could Lower Treatment Costs in Ovarian Cancer - ChemoFx
"...In the study, the authors assumed, for the sake of analysis, that the "outcomes are likely no worse when chemoresponse testing is performed than when an empiric choice of regimen is made."
However, if, in currently ongoing studies, the assay helps clinicians choose more effective therapies and thus improve survival, it would be "very attractive from a health economics perspective," say the authors, because the current study has already shown it to be cost effective."
The study was funded by Precision Therapeutics.
Karen Mason: Ovarian Cancer represented on Capitol Hill, Washington DC | Ovarian Cancer National Alliance
"Current treatments are brutal and consist of long “debulking” surgeries followed by months of chemotherapies..... During my nine years of survivorship, I have befriended many women who also had late-stage ovarian cancer. One by one, I have watched most of these women die...."
A genomic and transcriptomic approach for a differential diagnosis between primary and secondary ovarian carcinomas in patients with a previous history of breast cancer.
ABSTRACT:
BACKGROUND: The distinction between primary and secondary ovarian tumors may be challenging for pathologists. The purpose of the present work was to develop genomic and transcriptomic tools to further refine the pathological diagnosis of ovarian tumor after a previous history of breast cancer.
METHODS: Sixteen paired breast-ovary tumors from patients with a former diagnosis of breast cancer were collected.. ... A hierarchical clustering of these samples was performed, combined with a dataset of well-identified primary and secondary ovarian tumors.
RESULTS: In 12 of the 16 paired tumors analyzed, the comparison of genomic profiles confirmed the pathological diagnosis of primary ovarian tumor (n = 5) or metastasis of breast cancer (n = 7). Among four cases with uncertain pathological diagnosis, genomic profiles were clearly distinct between the ovarian and breast tumors in two pairs, thus indicating primary ovarian carcinomas, and showed common patterns in the two others, indicating metastases from breast cancer.
CONCLUSIONS: In patients with ovarian carcinoma and a previous history of breast cancer, SNP array analysis can be used to distinguish primary and secondary ovarian tumors. Transcriptomic analysis may be used when primary breast tissue specimen is not available.
Genetic/Familial high-risk assessment: breast and ... [J Natl Compr Canc Netw. 2010] - PubMed result
Abstract
Overview
All cancers develop as a result of mutations in certain genes, such as those involved in the regulation of cell growth and/or DNA repair,(1,2) but not all of these mutations are inherited from a parent. For example, sporadic mutations can occur in somatic/tumor cells only, and de novo mutations can occur for the first time in a germ cell (i.e., egg or sperm) or in the fertilized egg itself during early embryogenesis. However, family studies have long documented an increased risk for several forms of cancer among first-degree (i.e., parents, siblings, and children) and second-degree relatives (i.e., grandparents, aunts or uncles, grandchildren, and nieces or nephews) of affected individuals. These individuals may have an increased susceptibility to cancer as the result of 1 or more gene mutations present in parental germline cells; cancers developing in these individuals may be classified as hereditary or familial cancers. Hereditary cancers are often characterized by mutations associated with a high probability of cancer development (i.e., a high penetrance genotype), vertical transmission through either mother or father, and an association with other types of tumors.(3,4) They often have an early age of onset and exhibit an autosomal dominant inheritance pattern (i.e., occur when the individual has a mutation in only 1 copy of a gene). Familial cancers share only some features of hereditary cancers. For example, although familial breast cancers occur in a given family more frequently than in the general population, they generally do not exhibit the inheritance patterns or onset age consistent.
Vismodegib, a small-molecule inhibitor of the hedgehog pathway for the treatment of advanced cancers
"Vismodegib is currently undergoing phase II clinical trials for the treatment of advanced BCC, metastatic colorectal cancer, ovarian cancer, MB and other solid tumors. Because of its low toxicity and specificity for the Hh (hedgehog) pathway, this drug has potential advantages compared with conventional chemotherapy, and may also be used in combination treatments. Clinical trials with other Hh inhibitors are also ongoing and their therapeutic potential will need to be compared with vismodegib."
Attitudes Toward Information About Genetic Risk for Cognitive Impairment After Cancer Chemotherapy: Breast Cancer Survivors Compared With Healthy Controls
Conclusion
Results suggest lessened enthusiasm for genetic information that maintains or increases uncertainty about a specific course of action and highlight the importance of including clinically relevant groups in treatment decision-making research that employs hypothetical scenarios. Although women generally believe it is important to receive genetic information, they might benefit from assistance (eg, decision aid) in the difficult task of integrating information about survival and risk for adverse late effects from cancer treatment.
Pegylated Liposomal Doxorubicin and Carboplatin Compared With Paclitaxel and Carboplatin for Patients With Platinum-Sensitive Ovarian Cancer in Late Relapse
Pegylated Liposomal Doxorubicin and Carboplatin Compared With Paclitaxel and Carboplatin for Patients With Platinum-Sensitive Ovarian Cancer in Late Relapse
ABSTRACT
Purpose This randomized, multicenter, phase III noninferiority trial was designed to test the efficacy and safety of the combination of pegylated liposomal doxorubicin (PLD) with carboplatin (CD) compared with standard carboplatin and paclitaxel (CP) in patients with platinum-sensitive relapsed/recurrent ovarian cancer (ROC).
Patients and Methods Patients with histologically proven ovarian cancer with recurrence more than 6 months after first- or second-line platinum and taxane-based therapies were randomly assigned by stratified blocks to CD (carboplatin area under the curve [AUC] 5 plus PLD 30 mg/m2) every 4 weeks or CP (carboplatin AUC 5 plus paclitaxel 175 mg/m2) every 3 weeks for at least 6 cycles. Primary end point was progression-free survival (PFS); secondary end points were toxicity, quality of life, and overall survival.
Results Overall 976 patients were recruited. With median follow-up of 22 months, PFS for the CD arm was statistically superior to the CP arm (hazard ratio, 0.821; 95% CI, 0.72 to 0.94; P = .005); median PFS was 11.3 versus 9.4 months, respectively. Although overall survival data are immature for final analysis, we report here a total of 334 deaths. Overall severe nonhematologic toxicity (36.8% v 28.4%; P < .01) leading to early discontinuation (15% v 6%; P < .001) occurred more frequently in the CP arm. More frequent grade 2 or greater alopecia (83.6% v 7%), hypersensitivity reactions (18.8% v 5.6%), and sensory neuropathy (26.9% v 4.9%) were observed in the CP arm; more hand-foot syndrome (grade 2 to 3, 12.0% v 2.2%), nausea (35.2% v 24.2%), and mucositis (grade 2-3, 13.9% v 7%) in the CD arm.
Conclusion To our knowledge, this trial is the largest in recurrent ovarian cancer and has demonstrated superiority in PFS and better therapeutic index of CD over standard CP.
Abstracts 2010 ASCO Annual Meeting
search terms: "ovarian cancer' (note some duplication/non relevance) The abstracts can be search a variety of ways: eg. gynecologic cancer, brca, etc...
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