Monday, May 31, 2010
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 ]
The 5 Dumbest Cancer Myths? The 5 Dumbest Cancer Myths? PDF Print E-mail Written by Dr Vasilev Monday, 17 August 2009
HUYA Bioscience International forms strategic partnership with School of Chinese Materia Medica of BUCM
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: "The Mailys" Voting - May 2010
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
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
"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."
"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."
abstract/professional comments: Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial
Saturday, May 29, 2010
CCR Clinical Trials at NIH: Clinical Research: Search for Clinical Trials at NIH ovarian cancer Results = 5
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.
These results illustrate the need for improved methods for predicting functional ESEs and the potential consequences of sequence variants contained therein.
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
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.
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.
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.
Note: financial news
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
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.
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
"...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.
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
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
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
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.
WASHINGTON — A new screening approach to detect early stage ovarian cancer in post-menopausal women has proven promising, researchers said of results to a study released Thursday.
"More than 70 percent of ovarian cancers are diagnosed when they have already grown to an advanced stage, so identifying a reliable screening test for early-stage disease would be like finding the Holy Grail," said the study's lead author Karen Lu, of the University of Texas' Anderson Cancer Center.
"This study is one step forward in that direction. If confirmed in larger studies, this approach could be a useful and relatively inexpensive tool for detecting ovarian cancer in its early, more curable stages," she said.
The results were presented by the American Society of Clinical Oncology (ASCO) ahead of its annual conference, to be held June 4-8 in Chicago.
The new method uses a mathematical model to assess trends in CA-125 blood test results -- a protein known to rise during the cancer's development -- and a patient's age. The model is then "followed by transvaginal ultrasound and referral to a gynecologic oncologist, if necessary," researchers said.
For up to eight years, the study followed 3,238 post-menopausal women aged 50 to 74 who had no significant family history of breast or ovarian cancer, and the accuracy of using the mathematical model followed by ultrasound was 99.7 percent, indicating few false-positives using the approach, researchers said.
A larger study involving more than 200,000 women is currently underway in Britain, with results expected by 2015.
Society of Gynecologic Oncologists Releases 'Gynecologic Oncology 2010: State of the Subspecialty' Survey Results -- CHICAGO, May 18 /PRNewswire-USNewswire/ --
Highlights from the survey include:
- A movement in the profession to younger-aged practitioners and a larger number of women entering the specialty;
- A shift away from private practice as the primary practice setting into salaried positions and an increase in group or multi-specialty practice from individual practice;
- An increase in the number of medical assistants, nurse practitioners and physician assistants employed in gynecologic oncology practices;
- A continued dedication to providing chemotherapy services to patients regardless of the changes in reimbursement rates, as well as the continuation of enrollment of patients into cooperative studies versus the more revenue neutral or positive industry-sponsored trials;
- The positive effect of caps on non-economic and total damages on the cost of medical liability/malpractice insurance; and the
- An overall willingness of gynecologic oncologists to accept/treat women with a gynecologic cancer without knowledge of insurance coverage and the preponderance of Medicare and Medicaid patients seen in a practice, versus private insurance.
Reference to ovarian cancer:
10. Eisenhauer EL, Tew WP, Levine DA et al. Response and outcomes in elderly patients with stages IIIC-IV ovarian cancer receiving platinum-taxane
chemotherapy. Gynecol Oncol 2007;106:381–387.
High cumulative incidence of cancer in patients with cardio-renal-anaemia syndrome (chronic kidney disease)
The combination of chronic kidney disease (CKD), chronic heart failure (HF), and anaemia, the so-called cardio-renal-anaemia syndrome (CRA) is associated with dysregulation of erythropoietin levels and inflammation. Both have been associated with the development of cancer. This study aimed to determine the cumulative incidence of cancer in patients with CRA, as compared with anaemic CKD and control patients.
Note: this is not 'new' news
"Radon, a radioactive, invisible, odorless gas that comes from the decay of naturally occurring uranium in the earth's soil, can accumulate in enclosed areas, such as underground mines and homes. It is the second leading cause of lung cancer in the United States and the leading cause of lung cancer among people who have never smoked, according to the report."
Impact of caregivers’ unmet needs for supportive care on quality of terminal cancer care delivered and caregiver’s workforce performance
Caregivers’ unmet needs negatively affected both the quality of EOL care they delivered and their workplace performance. More investment in caregiver support and public policies that meet caregiver needs are needed, and hospice use should be encouraged.
"Few studies have assessed sexuality in the advanced stage of disease. Nevertheless, advanced cancer patients are willing to talk about their sex lives and the impact of the disease on their sexual function."
define: gonadotropin - hormone secreted by the anterior pituitary gland and placenta; stimulates the gonads and controls reproductive activity
Harvard Reproductive Endocrine Sciences Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Isolated gonadotropin-releasing hormone (GnRH) deficiency is a treatable albeit rare form of reproductive failure that has revealed physiological mechanisms controlling human reproduction, but despite substantial progress in discovering pathogenic single-gene defects, most of the genetic basis of GnRH deficiency remains uncharted. Although unbiased genetic investigations of affected families have identified mutations in previously unsuspected genes as causes of this disease in some cases, their application has been severely limited because of the negative effect of GnRH deficiency on fertility; moreover, relatively few of the many candidate genes nominated because of biological plausibility from in vitro or animal model experiments were subsequently validated in patients. With the advent of exciting technological platforms for sequencing, homozygosity mapping, and detection of structural variation at the whole-genome level, human investigations are again assuming the leading role for gene discovery. Using human GnRH deficiency as a paradigm and presenting original data from the screening of numerous candidate genes, we discuss the emerging model of patient-focused clinical genetic research and its complementarities with basic approaches in the near future.
Saturday, May 22, 2010
NKTR-102 Phase 2 Clinical Data Accepted for Oral Presentation at 2010 ASCO... -- SAN CARLOS, Calif., May 20 /PRNewswire-FirstCall/ --
Nektar To Host Investor Breakfast at ASCO on Monday, June 7, 2010
Nektar will also webcast a presentation to investors and analysts to be held at the 2010 ASCO Meeting on Monday, June 7, 2010 at 8 AM Central Time.
Panelists at the investor event will include:
* Ignace Vergote, M.D., Ph.D., Head of the Department of Obstetrics and Gynaecology and Gynaecologic Oncology at the Catholic University of Leuven, Belgium;
* Robert Coleman, M.D., Director of Clinical Research, Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; and
* Daniel Von Hoff, M.D., F.A.C.P., Chief Scientific Officer, TGen Clinical Research Services at Scottsdale Healthcare and U.S. Oncology, and Clinical Professor of Medicine at the University of Arizona College of Medicine and 2010 recipient of the ASCO David A. Karnofsky Memorial Award Lecture.
The event will be accessible live and by replay and can be accessed from the homepage of the company's website at www.nektar.com beginning on June 7, 2010 at 8:00 AM Central Time.
podcast: CA-125 Change Over Time Shows Promise as Screening Tool for Early Detection of Ovarian Cancer
CA-125 Change Over Time Shows Promise as Screening Tool for Early Detection of Ovarian CancerBlood test currently approved to find recurrence full of new possibility; invasive, high-grade disease uncovered at curable stage
MD Anderson News Release 05/20/10
Note: full free access; includes risks of Li-Fraumeni, Cowden and Lynch Syndromes
PLoS ONE: Repertoire of microRNAs in Epithelial Ovarian Cancer as Determined by Next Generation Sequencing of Small RNA cDNA Libraries
Note: full free access / technical
MicroRNAs (miRNAs) are small regulatory RNAs that are implicated in cancer pathogenesis and have recently shown promise as blood-based biomarkers for cancer detection. Epithelial ovarian cancer is a deadly disease for which improved outcomes could be achieved by successful early detection and enhanced understanding of molecular pathogenesis that leads to improved therapies. A critical step toward these goals is to establish a comprehensive view of miRNAs expressed in epithelial ovarian cancer tissues as well as in normal ovarian surface epithelial cells.
This report expands the body of miRNAs known to be expressed in epithelial ovarian cancer and provides a useful resource for future studies of the role of miRNAs in the pathogenesis and early detection of ovarian cancer.
DiscussionThe work reported here was motivated by the hypothesis that the entire repertoire of miRNAs expressed in ovarian cancer, including potentially tissue- and cancer-specific miRNAs, had not yet been elucidated.
Vitamin D receptor rs2228570 polymorphism and invasive ovarian carcinoma risk: Pooled analysis in five studies within the Ovarian Cancer Association Consortium
"This pooled analysis provides further evidence that the VDR rs2228570 polymorphism might influence ovarian cancer susceptibility."
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Perioperative morbidity and outcome of secondary cytoreduction for recurrent epithelial ovarian cancer.
Secondary cytoreduction in relapsed ovarian cancer is safe and feasible and perioperative outcome is not inferior compared to primary cytoreduction. Surgery-associated morbidity should represent a minor aspect in the selection and counselling of patients regarding treatment options for recurrent ovarian cancer.
Abstract OBJECTIVE: The purpose of this article is to review the role of FDG PET/CT in ovarian cancer, which is the leading cause of death among gynecologic cancers. CONCLUSION: FDG PET/CT can significantly modify the assessment of the extent of primary and recurrent ovarian cancer and, hence, often alters patient management substantially. FDG PET/CT has thus become a critical tool for the preoperative evaluation of women with primary ovarian cancer and for postoperative follow-up assessment for evidence of recurrence in these patients.
Pre-counseling Education for Low Literacy Women at Risk of Hereditary Breast and Ovarian Cancer (HBOC): Patient Experiences Using the Cancer Risk...
Pre-counseling Education for Low Literacy Women at Risk of Hereditary Breast and Ovarian Cancer (HBOC): Patient Experiences Using the Cancer Risk Education Intervention Tool (CREdIT)
Thursday, May 20, 2010
"Background: Oncologists often do not give honest prognostic and treatment-effect information to patients with advanced disease. One of the primary reasons stated for witholding this information is to “not take away hope.” We could find no study that tested if hope was influenced by honest clinical information...cont'd"
Note: once the form is filled out the paper uploads a pdf file of the report automatically
ORC’s Oncology Report examines three important Oncology issues: Assessing the Impact of Revised NSCLC Staging, Genetically Linked Breast Cancer and PARP-1 Inhibitors and Reactions to New Mammogram Recommendations. Submit the information below and download the full report.
* ''Biochemistry'' is the study of the chemical substances and vital processes occurring in living organisms. Biochemists focus heavily on the role, function, and structure of biomolecules. The study of the chemistry behind biological processes and the synthesis of biologically active molecules are examples of biochemistry.
* ''Genetics'' is the study of the effect of genetic differences on organisms. Often this can be inferred by the absence of a normal component (e.g. one gene). The study of "mutants" – organisms which lack one or more functional components with respect to the so-called "wild type" or normal phenotype. Genetic interactions (epistasis) can often confound simple interpretations of such "knock-out" studies.
* ''Molecular biology'' is the study of molecular underpinnings of the process of replication, transcription and translation of the genetic material. The central dogma of molecular biology where genetic material is transcribed into RNA and then translated into protein, despite being an oversimplified picture of molecular biology, still provides a good starting point for understanding the field. This picture, however, is undergoing revision in light of emerging novel roles for RNA.
Wednesday, May 19, 2010
These data support the validity of My Family Health Portrait pedigrees for four common conditions-diabetes and colon, breast, and ovarian cancer.
Tuesday, May 18, 2010
Objectives. Cancer and type 2 diabetes (T2D) are two common diseases that may share risk factors. We aimed at determining subsequent cancer risks in patients hospitalized for T2D in Sweden.
Methods. T2D patients were obtained from the nationwide Hospital Discharge Register; cancers were recorded from the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for cancer
following last hospitalization for T2D. The comparison group was the general Swedish population.
Results. The number of hospitalized T2D patients from 1964 to 2007 was 125,126, of whom 26,641 had an affected family member. Altogether 24 cancers showed an elevated risk when follow-up was started after the
last hospitalization. The highest SIRs were for pancreatic (6.08) and liver (4.25) cancers. The incidences of these cancers were even elevated when follow-up was started 5 years after the last hospitalization for T2D, with primary liver cancer showing the highest SIR of 4.66. Also increased were the incidences of upper aerodigestive tract, esophageal, colon, rectal, pancreatic, lung, cervical, endometrial, ovarian, and kidney cancers. Prostate cancer showed a lower risk. Familial T2D patients showed no exceptional elevated cancer risks but their prostate cancer and melanoma risks were lower.
Conclusions. This study, covering approximately one half of Swedish T2D patients, showed an elevated risk for several cancers after hospitalization for T2D, probably indicating the profound metabolic disturbances of the underlying disease. The highest risks were found for
liver and pancreatic cancers. No excess cancer risks were observed in familial diabetics. The lower risk for prostate cancer remains intriguing
(ovarian cancer incidence rates 15.61/per 100,000 population; risk 1.84 (>1.0 = increased risk)
Health care professionals who join the National Cancer Institute Clinical Trials at NIH mailing list receive: * Quarterly e-mail notifications about clinical trials * Information about the National Cancer Institute's programs and clinical opportunities
".......“Patient refusal rates may be less of a problem than low rates of trial offers,” wrote the authors."
Additional Clinical Trials Resources
Cancer Clinical Trials at NIHNCI supports cancer clinical trials across the country (U.S) through its extramural research program. Meanwhile, on NIH’s main campus, the Institute’s intramural researchers in the Center for Cancer Research (CCR) conduct hundreds of trials each year at the NIH Clinical Center in Bethesda, MD, and these trials often differ from those available elsewhere.
While some cancer centers also offer early-stage clinical trials, the difference is that CCR focuses almost exclusively on early-stage trials, said Dr. Bill Dahut, CCR’s clinical director.
NCI’s intramural program is able to pay the transportation costs for patients who are enrolled in Clinical Center trials. This allows CCR to see many more patients with rare cancers, or rare subtypes of common cancers, than other research sites because CCR can fly in patients from around the country to be treated in investigational studies.
One commonly cited barrier to entering clinical trials is the worry among both patients and their physicians of losing control. “An important point about treatment at NCI is that everything we do here for patients is done in close collaboration with their local physicians back home,” Dr. Dahut explained. “Our physicians provide expert clinical care to patients while they are being treated on protocol at NCI, but our physicians can see patients only while they are at the Clinical Center. Thus, continued care by local physicians is incredibly important to allow patients to access standard treatments or other trials not available here. Local physicians must remain closely involved with patients on NCI studies because side effects, from the cancer or the therapy, may occur when the patient is home and far from Bethesda.”
Patients and physicians interested in exploring cancer clinical trials at NIH can visit CCR’s clinical trials Web site. The site includes detailed descriptions of clinical trials currently recruiting patients; information for the general public about clinical trials and participating in trials at NCI; and information for health professionals about referring patients, the Center’s clinical programs and investigators, and ways to keep up to date with CCR research and opportunities.
“We’d really like to encourage physicians to join our mailing list,” said Susan McMullen, patient outreach and recruitment coordinator for CCR’s Office of the Clinical Director. “One of the barriers to recruiting patients at NIH is that our doctors don’t have a patient base outside of clinical trials to draw from, so we rely on community doctors to refer patients to us.”
Family Cancer Registries
To determine what genetic factors may be at work and how environmental influences alter those genetic risks, researchers rely on those affected by familial cancer to participate in family cancer registries.
“Our major goal in studying these families is to identify what are called high-risk susceptibility genes,” explained Dr. Peggy Tucker, director of the Human Genetics Program and chief of the Genetic Epidemiology Branch in NCI’s Division of Cancer Epidemiology and Genetics (DCEG). “We then try to understand the function of those genes, how they confer risk, and what other factors within the family modify risk.
“Ultimately, we want to be able to alter the risk of cancer in these families either by identifying susceptibility factors we can modify—for example, avoiding sun exposure in melanoma families—or designing interventions that can affect risk—such as prophylactic oophorectomy for women in families with high risk of both breast and ovarian cancer,” she said.
Family cancer registry studies can also help inform researchers about cancer susceptibility risks in the general population. For example, researchers identified dysplastic nevi as a major risk factor for melanoma by studying families at high risk of melanoma.
Researchers at NCI first began conducting family registry studies in the mid-1960s. These long-term studies follow families through successive generations, and allow researchers to examine the role of inherited high-susceptibility genes and cancer. Today, DCEG researchers are studying families with a number of inherited cancers or cancer-susceptibility syndromes, and researchers in NCI’s Division of Cancer Control and Population Sciences (DCCPS) sponsor the Breast and Colon Cancer Family Registries.
Whereas DCEG’s family registries are conducted at the NIH Clinical Center, the family registries based in DCCPS are found throughout the United States, Australia, and Canada. “Currently, we have about 78,000 men and women from nearly 26,000 families participating in these registries,” said Dr. Sheri Schully, program officer for the DCCPS family registries program. “The main objective of these registries is to identify and characterize cancer susceptibility genes, but the investigators also look at gene–gene and gene–environment interactions as well.”
Although family registry studies do not provide treatment to participating families, investigators often provide test results that can help family members learn which of them may be at higher risk because of certain susceptibility genes, such as mutations in the BRCA1 and BRCA2 genes or those associated with Lynch syndrome, said Dr. Schully.
Additionally, the studies are an opportunity for people who are often desperate for answers to ask questions.
“We like to think it’s a positive experience for them because they have a whole day at NIH to meet with physicians and nurses who know a lot about the disease,” Dr. Tucker explained. “We try to keep them updated with new findings about the diagnosis and management of the cancer that affects their family, and they know they can always come to us for referrals for care of the disorders that we’re studying.”
Learn More About Clinical Trial Enrollment....
Breast Cancer Research | Full text | Familial relative risks for breast cancer by pathological subtype: a population-based cohort study
"We may conclude from our results that the FRR (familial relative risk) for breast cancer is significantly increased for each pathological subtype except TN tumours, although the numbers in the latter category were too small to draw definitive conclusions.
When analyzed by tumour subtype, a surprisingly high proportion of FRR (familial relative risk) for ER-negative disease is already explained.
We estimate that 32% of breast cancer FRR for ER-negative disease is explained by BRCA1 and BRCA2 mutations alone.
Patients carrying such mutations may be advised to undergo prophylactic therapies such as oophorectomy or mastectomy.
About 10% of the FRR for ER-positive disease is explained by 12 newly discovered SNPs, and the contributions of these SNPs to FRR are likely to be somewhat higher once the true causal variants are identified.
The construction of informative risk prediction models for ER-positive disease is particularly important as the risk of ER-positive disease can be reduced by chemoprevention such as tamoxifen.
It is possible that including novel (new) genetic variants associated with breast cancer susceptibility in models may improve risk prediction for subtype specific disease."
BSB4uD (Be Smart Before You Donate - see blog posting and income comparisons non-profit employees vs professional salaries) - note updated information on Canadian family physician salaries - average
Blogger Author's Opinion: based on these averages, most family physicians are underpaid
Family Physician salaries as per CMAJ April 9th 2010: $225,521. Cdn avg CMAJ
Update: May 18th, 2010
A separate, unpublished CIHI indice which weights all payments — whether fee-for-service, salary or other form of capitation — for all services, against a national median indicates that Newfoundland and Labrador doctors essentially earn 6.78% less than a national median of $224 875 earned by doctors in 2007–08. On that scale, doctors in Alberta (7.22% above the median) were the highest paid in the country, followed by those in British Columbia (5.84% above), New Brunswick (4.6% above), Saskatchewan (4.24% above), Nova Scotia (1.68% above), Ontario (1.68% below) and Manitoba (4.88% below). Only doctors in Prince Edward Island (18.28% below) and Quebec (28.66% below) earned less than those in Newfoundland and Labrador.
Function: (ref source WIKI) EpCAM is a pan-epithelial antigen that is expressed on almost all carcinomas. Its constitutional function is being elucidated.Note: search blog for other references to EpCAM and in particular to Lynch Syndrome
"...Like for every targeted therapy, the level of EpCAM target expression will have an impact on the outcome of a trial. This was evident for the human anti-EpCAM antibody adecatumumab in patients with metastatic breast cancer. Although a high level and frequency of EpCAM expression can be assumed for patients with colorectal cancer, none of the previous trials prospectively or retrospectively analyzed patients for levels of EpCAM expression on tumor tissue. Particularly for a low-affinity antibody, such as edrecolomab, it may be of importance that tumor cells express EpCAM at a high and not just at an intermediate level..... Future studies will certainly benefit from stratifying patients for their level of EpCAM target expression."
Warfarin is a blood-thinning medication that helps treat and prevent blood clots. There is no specific warfarin (Coumadin) diet. However, certain foods and beverages can make it so warfarin doesn't effectively prevent blood clots. It's important to pay attention to what you eat while taking warfarin.
One nutrient that can lessen warfarin's effectiveness is vitamin K. It's important to be consistent in how much vitamin K you get daily. The average daily allowance of vitamin K for adult men is 120 micrograms (mcg). For adult women, it's 90 mcg. While eating small amounts of foods that are rich in vitamin K shouldn't cause a problem, avoid eating or drinking large amounts of:
- Brussels sprouts
- Collard greens
- Mustard greens
- Green tea
DefinitionBy Mayo Clinic staff A stem cell transplant is the infusion of healthy stem cells into your body. A stem cell transplant may be necessary if your bone marrow stops working and doesn't produce enough healthy stem cells. A stem cell transplant can help your body make enough healthy white blood cells, red blood cells or platelets, and reduce your risk of life-threatening infections, anemia and bleeding.
Although the procedure to replenish your body's supply of healthy blood-forming cells is generally called a stem cell transplant, it's also known as a bone marrow transplant or an umbilical cord blood transplant, depending on the source of the stem cells. Stem cell transplants can use cells from your own body (autologous stem cell transplant) or they can utilize stem cells from donors (allogenic stem cell transplant).
Retrospective comparison of patient outcomes after in-person and telephone results disclosure counseling for BRCA1/2 genetic testing.
"This study suggests that telephone results disclosure is clinically appropriate when counselors utilize their clinical judgment to determine which patients are appropriate candidates."
The predictive value of serum VEGF in multiresistant ovarian cancer patients treated with bevacizumab (Avastin)
Single agent bevacizumab has activity in ovarian cancer patients. Pre-treatment serum VEGF seems to have predictive value.
A Comparison of Quality-of-Life Domains and Clinical Factors in Ovarian Cancer Patients: A Gynecologic Oncology Group Study
Ovarian cancer patients have decreased QOL in physical, functional, and emotional domains; however, they may compensate with increased social support. At the time of diagnosis and treatment, patients' QOL is affected by inherent characteristics. Assessment of treatment outcomes should take into account the effect of these independent variables.
Comparison of a novel multiple marker assay vs the Risk of Malignancy Index for the prediction of epithelial ovarian cancer in patients with a pelvic
"CONCLUSION: The dual marker algorithm utilizing HE4 and CA125 to calculate a ROMA value achieves a significantly higher sensitivity for identifying women with EOC than does RMI."
"The prevention of epithelial ovarian cancer (EOC) is of particular interest given its high mortality rate and the lack of a cost-effective screening program. OC (oral contraceptives) usage significantly diminishes the incidence of EOC, in both the general population, as well as in patients with BRCA 1 or 2 mutations. Risk reduction is greatest with prolonged usage and persists for more than 30 years after OC use, but diminishes over time. Prospective, randomized trials, designed to control for all known variables, are mandatory to fully assess the potential for hormonal chemoprevention in breast, endometrial and ovarian cancers."
Multicentric parallel phase II trial of the polo-like kinase 1 inhibitor BI 2536 in patients with advanced head and neck cancer, breast cancer, ovarian cancer, soft tissue sarcoma and melanoma. The first protocol of the European Organization for Research and Treatment of Cancer (EORTC) Network Of Core Institutes (NOCI)
CONCLUSIONS: BI 2536 showed limited antitumour activity according to the design of this trial in five different tumour types. Derivatives of BI 2536 with a more favourable pharmacological profile are currently explored further in prospective studies.
JCO -- Early Release CORRESPONDENCE Accrual Strategies for Cancer Genetics Research: Blurred Boundaries (ethics)
Accrual Strategies for Cancer Genetics Research: Blurred Boundaries
Daniel Rayson and Karen A. Gelmon JCO published online May 17, 2010, DOI:10.1200/JCO.2010.29.0759 [PDF]
TO THE EDITOR:
Metcalfe et al1 describe the incidence of BRCA1 and BRCA2 founder mutations in an unselected group of Ashkenazi Jewish women, with an astounding 2,000 women enrolled within 14 days of an article appearing in one of Canada’s most respected newspapers. Given the overwhelming interest amongthe target population, one might ask exactly what information prompted such an overwhelming response. The article in question was published on the front page of the Toronto Globe and Mail (Saturday May 24, 2008) with a large-font headline reading: “Cancer test a genetic crystal ball for Jewish women.” The first line in the piece stated: “For the first time in Canada, Jewish women will be offered the chance to alter their genetic destiny by taking a test…” a patently untrue and sensationalistic statement, given that presymptomatic BRCA1 and BRCA2 mutation testing, including Ashkenazi Jewish founder mutations, have been available for many years through medical genetics services nationwide." "The study by Metcalfe et al has accentuated these concerns and should serve as a basis for additional discussion in the oncology and
medical genetics communities regarding appropriate methodologies or recruitment to clinical investigations in cancer genetics."
Response to D. Rayson et al - re: Correspondence - Accrual strategies for cancer genetics research: blurred boundaries (ethics)
"If Drs Rayson and Gelmon1 are under the impression that we
have influence over how the Globe and Mail2 chooses to present its
news items, they are mistaken—perhaps their comments should be
addressed to the Globe Editorial office. We too are frustrated by the
incessant optimism of the media when they enter into the realms of
genetics or oncology—each gene discovery ineluctably will lead to a
treatment of a devastating genetic disease, each new molecule is a
target for a new cancer drug—but we suppose that unfettered optimism
is good for the newspaper business and is included in the price
we pay for freedom of the press...."
If the opinions of Drs Rayson and Gelmon are representative of the medical communities of Nova Scotia and British Columbia, then it is unlikely that populationbased genetic screening for Jewish women will be introduced in those provinces any time soon."
1. Rayson D, Gelmon KA: Accrual strategies for cancer genetics research:
blurred boundaries. J Clin Oncol doi: 10.1200/JCO.2010.29.0759
2. Cancer test a genetic crystal ball for Jewish women. Toronto Globe and
Mail, Saturday May 24, 2008
3. Metcalfe KA, Poll A, Royer R, et al: Screening for founder mutations in
BRCA1 and BRCA2 in unselected Jewish women. J Clin Oncol 28:387-391, 2010
DOI: 10.1200/JCO.2010.29.1146; published online ahead of print at
www.jco.org on May 17, 2010
OvPlex website: OvPlex™ targets symptomatic women and has been designed as a simple blood test for earlier diagnosis of ovarian cancer and is statistically significantly better than CA125 alone (the current standard blood test) in the detection of ovarian cancer. OvPlex™ outperforms CA125 for the detection of ovarian cancer in all stages of the disease - particularly, early stage. As mentioned, if a woman is diagnosed with ovarian cancer at an early stage of the disease, five year survival rates are greatly increased.
Official Title: “E-health Intervention for Cancer Survivors”
* Behavioral: Project Onward website + social network
* Behavioral: Project Onward website + Coach
* Behavioral: Project Onward website
This study will develop and examine the effectiveness of an intervention that utilizes multiple telecommunications technologies to improve cancer survivors' access to mental health care and increase their ability to manage the high risk transition time from active cancer treatment to survivorship. The intervention, referred to as Project Onward, uses an interactive website, e-mail, telephone, and an online social network. The purpose of this study is to pilot a novel intervention that can reduce costs, examine methods to improve adherence to internet based treatment and overcome numerous barriers to treatment for mental health concerns.
Monday, May 17, 2010
Aeterna Zentaris Receives Positive Opinion for Orphan Medicinal Product Designation for AEZS-108 for the Treatment of Ovarian Cancer from the Committe
media: Aeterna Zentaris Receives Positive Opinion for Orphan Medicinal Product Designation for AEZS-108 for the Treatment of Ovarian Cancer from the Committee for Orphan Medicinal Products of the European Medicines Agency
Keeping the GINA in the bottle: asessing the current need for genetic non-discrimination legislation in Canada - full access
"The background to the adoption of the Genetic Information Nondiscrimination Act (GINA) in the United States has important lessons for Canada, especially in view of the increasing tread toward privatized services within the Canadian public health care system. When the US legislation was finally adopted in May 2008, observers rejoiced that “[a]t last, the United States has a federal law that protects consumers from discrimination by health insurers and employers on the basis of genetic information.”1 GINA is the culmination of a long process that began in 1995 when federal lawmakers first introduced the legislation. In the interim, more than 45 American states had passed their own genetic nondiscrimination laws.2
Such a high level of legislative activity indicates a deep and abiding public concern about the issue of genetic discrimination. Yet the same level of angst has yet to make its way north. Although a recent Canadian study reports on perceptions of genetic discrimination with regard to people at risk for Huntington’s disease,3 discussion of the general issue in Canada has been limited and is focused primarily on discrimination in the context of life insurance.4 More significantly, there is no legislation comparable to GINA at either the federal or the provincial/territorial level in Canada. Does the absence of such legislation mean that Canadians are at higher risk of genetic discrimination than Americans? Does Canada require similar legislation?"
Search of: ovarian cancer | Open Studies | received from 04/01/2010 to 05/17/2010 - List Results - ClinicalTrials.gov
Found 25 studies with search of: ovarian cancer - Open Studies - received from 04/01/2010 to 05/17/2010
amednews: Hospitals exchange of cost data clears antitrust hurdle :: May 17, 2010 ... American Medical News
"Quality-adjusted pricing also should be taken into account, he said. "From an antitrust perspective, when dealing with a service industry ... just looking at cost may say very little."
amednews: Informed consent: Hospitals explore personalizing risks :: May 17, 2010 ... American Medical News
"It is well-known from the medical literature that informed consent is neither informed nor consensual," said John Spertus, MD, MPH"
"The (web)site (now closed down)claimed the powder was the experimental cancer drug sodium dichloroacetate (DCA)
Sunday, May 16, 2010
"It has been 10 years since the Institute of Medicine released its damning report, To Err is Human, but it has been 24 centuries since Hippocrates admonished physicians to do no harm," said Dennis S. O'Leary, MD, president emeritus of The Joint Commission and a founding member of the Lucian Leape Institute. "Today, although some progress in improving patient safety continues to be made, healthcare remains fundamentally unsafe as up to one in 10 people admitted to hospitals continue to experience significant, preventable adverse events."
Note: to use the Online Meeting Program registration is required (free).
Online Meeting Program
Use the online Meeting Program to search the complete program listings of sessions and abstract titles. The online Meeting Program will be updated frequently, so use this tool for access to the most up to date information. Once you have found sessions you are interested in attending, you can also build an itinerary.
2010 ASCO Annual Meeting | Meeting Program | What Is New This Year 2010 annual meeting - Trials in Progress Poster Session
Note: the program is now online for the annual meeting June 2010 (searchable) (http://www.asco.org)
What's New This Year
Trials in Progress Poster Session
The new Trials in Progress Poster Session will facilitate awareness of and dialogue about open, ongoing clinical trials. It differs from other Poster Sessions in that
* outcomes data or results are not included
* the goal is to promote discussion among trial investigators, to encourage recruitment of new investigators or sites, and to stimulate discussion of successor or confirmatory trials
* the focus is on the background of the science behind the trial, and preclinical or earlier-phase data (preferably with references) is encouraged
The Trials in Progress Poster Session will be held Monday, June 7 from 8:00 AM to 12:00 PM. All Meeting attendees are welcome to attend this new session.
abstract: miR-20a promotes proliferation and invasion by targeting APP in human ovarian cancer cells.
define: microRNA - A short piece of single-stranded RNA that does not encode a protein and controls the expression of genes.
MicroRNAs (miRNAs) are emerging as a class of small regulated RNAs, and the alterations of miRNAs are implicated in the initiation and progression of human cancers. Our study shows that inhibition of miR-20a in OVCAR3 ovarian cancer cell line could suppress, whereas overexpression of miR-20a could enhance cell long-term proliferation and invasion. We also confirmed amyloid precursor protein (APP) as a direct target gene of miR- 20a. Furthermore, suppression of APP expression could also promote ovarian cancer cell proliferation and invasion, which is consistent with the results of miR-20a overexpression. Therefore, we concluded that the regulation of APP is an important mechanism for miR-20a to promote proliferation and invasion in ovarian cancer cells.
Saturday, May 15, 2010
Note: best viewed in Firefox browser
.....click on 'read more'
BRCA1, BRCA2 and CHEK2 c.1100 delC mutations in patients with double primaries of the breasts and/or ovaries
Expert Reviews full access: On the advent of MSI testing of all colorectal cancers and a substantial part of other Lynch syndrome-related neoplasms
Worldwide, more than 1 million people present with colorectal cancer (CRC) annually. Of these, 2–5% occur in the context of Lynch syndrome (LS), the most common hereditary CRC predisposing syndrome (formerly designated as hereditary nonpolyposis CRC [HNPCC]). LS is characterized by a high lifetime risk for the development of CRC (20–70%), endometrial cancer (15–70%) and other extracolonic cancers (<15%). These extracolonic malignancies include carcinomas of the small intestine, stomach, pancreas and biliary tract, ovarium, brain, upper urinary tract and skin. .......germline mutation in one of the MMR genes MLH1, MSH2, MSH6 or PMS2.
Owing to the MMR deficiency in LS tumors, a microsatellite instability (MSI) phenotype is present. MSI, however, is also found in approximately 10–13% of sporadic CRCs (in total, MSI is present in approximately 15% of all CRCs). In addition to MSI, most LS tumors lack expression in the tumor cell nuclei of one of the four MMR proteins, MLH1, MSH2, MSH6 or PMS2.
Early detection of LS is of great importance, particularly in presymptomatic mutation carriers, since colonoscopic surveillance has proven to reduce CRC morbidity and mortality by 65–70%  and prophylactic surgery may prevent endometrial and ovarium carcinoma effectively.
Different models and strategies have been developed to identify patients with LS. In 1990, the Amsterdam criteria I were developed to provide a basis for uniformity in collaborative studies to find the disease-causing gene. These criteria were designed to be highly specific at the expense of sensitivity. They were criticized because extra-colonic tumors were not taken into account, thereby excluding classical LS families....Therefore, the Amsterdam criteria II were established in 1999"
Hyperthermic intra-peritoneal chemotherapy using Oxaliplatin as consolidation therapy for advanced epithelial ovarian carcinoma. Results of a phase II
Using intra-peritoneal Oxaliplatin associated with hyperthermia as consolidation therapy for advanced ovarian cancer results in a high risk of grade 3 morbidities with only a small benefit on survival
Friday, May 14, 2010
Note: also see prior blog post on Type D personality as per below (date):
Saturday, January 23, 2010
full free access: Type D personality in the general population: a systematic review of health status, mechanisms of disease, and work-related problems "Type D personality in the general population: a systematic review of health status, mechanisms of disease, and work-related problems."
request a copy of the pdf presentation file via: firstname.lastname@example.org
abstract and free full text: How old is this mutation? - a study of three Ashkenazi Jewish founder mutations
The three mutations analyzed were MSH2*1906 G->C, APC*I1307K, and BRCA2*6174delT.
"Mutation age estimates (averages):
16.8 generations for MSH2
106 generations for I1037K
90 generations for 6174delT
Note: long article regarding efforts in progress
One specific area of importance to patients:
"As clinical trials become more complex, so do the concerns researchers must address. Original correlative trials have now led to a new generation of clinical trials, some of which exclude patients who do not possess the specific biomarker being studied. When these biomarker tests must be completed before enrollment onto a clinical trial, it is important that the study budget provide reimbursement for testing of individuals who are afterward deemed ineligible. Additionally, because biomarker testing is generally completed at a central laboratory designated by the sponsor, it is important that physicians know how long it will take to receive the results. If the turnaround time is 3 to 4 weeks, it should be considered whether patients will agree to wait that long to begin treatment, especially if they may ultimately be excluded from the clinical trial on the basis of the test results. Considerations such as these should be discussed in advance with the sponsor, so efforts can be made to expedite testing. The research site should also be aware of all options that can be provided to patients who are excluded from the clinical trial. Sometimes sponsors will offer an expanded access option or suggest alternative trials using the medication, important factors when enrollment onto the clinical trial is the only remaining treatment option for a patient."