- A high score based on the expression of 23 genes involved in repairing DNA damage after platinum-based chemotherapy for ovarian cancer was associated with improved survival.
- Note that the gene score outperformed clinical factors associated with ovarian cancer outcome and was the only baseline factor that had a significant association with overall survival.
Saturday, April 14, 2012
Religion, Spirituality, and Cancer: The Question of Individual Empowerment:
It has often been noted that people with a severe illness endeavor to deepen their religious and spiritual practice and knowledge. It is generally accepted that spiritual and religious factors help sick people confront their suffering. The authors conducted a qualitative research on the role of religious and spiritual practices and knowledge among 10 cancer patients in Québec, Canada. Individual interviews focused on their illness experience confirmed that religion and spirituality can be present and contribute to coping when life is threatened. More precisely, the analyses of the place and use of these resources during the patient’s illness showed that these resources contributed to an individual empowerment process that was undertaken in response to a biographic and existential disruption induced by the illness diagnosis. The sick people took advantage of religious and spiritual content in their quest for meaning and a cure, progressing from a stage of despair and powerlessness to a stage of hope, a critical analysis of the disease, and a better management and control of it and its evolution. This article describes how people suffering from cancer use and participate in religious and spiritual content. It demonstrates the contribution of this content to an individual empowerment process. The use of religion and spirituality constitutes a quest for self-mastery, an acquiring of power and control. We understand that religious and spiritual phenomena do not always prevent people from fighting against their suffering, limit their freedom, or systematically reduce people’s viewpoints and worldviews.
abstract: Vitamins, minerals, essential fatty acids and colorectal cancer risk in the United Kingdom Dietary Cohort Consortium - 2012 - International Journal of Cancer
Vitamins, minerals, essential fatty acids and colorectal cancer risk in the United Kingdom Dietary Cohort Consortium - International Journal of Cancer
The risk for colorectal cancer may be influenced by the dietary intake of various vitamins, minerals and essential fatty acids. We conducted a pooled analysis of dietary data collected using food diaries in seven prospective studies in the United Kingdom Dietary Cohort Consortium. Five hundred sixty-five cases of colorectal cancer were matched with 1,951 controls on study centre, age, sex and recruitment date. Dietary intakes of retinol, vitamin A, thiamin, riboflavin, vitamin B6, folate, vitamin B12, vitamin D, calcium, iron, magnesium, potassium, n − 6 fatty acids, n − 3 fatty acids and the ratio of n − 6 to n − 3 fatty acids were estimated and their associations with colorectal cancer examined using conditional logistic regression models, adjusting for exact age, height, weight, energy intake, alcohol intake, fiber intake, smoking, education, social class and physical activity. There were no statistically significant associations between colorectal cancer risk and dietary intake of any of the vitamins, minerals or essential fatty acids examined.
open access: Cancer screening in the United States, 2012 - Smith - 2012 - CA: A Cancer Journal for Clinicians - Wiley Online Library
Cancer screening in the United States, 2012 CA: A Cancer Journal for Clinicians
section related to ovarian cancer:
Testing For Early Ovarian Cancer Detection
Although the annual incidence of ovarian cancer is low compared with breast cancer and precursor lesions of the cervix, it is the most lethal of the gynecologic cancers.21 Fewer than one-half of women diagnosed with ovarian cancer survive longer than 5 years, and although the 5-year survival rate for patients with localized ovarian cancer is greater than 90%, only 15% of all patients are diagnosed with localized disease.5
Screening and diagnostic methods for ovarian cancer include pelvic examination, CA 125 antigen as a tumor marker, transvaginal ultrasound (TVU), and, potentially, multimarker panels and bioinformatic analysis of proteomic patterns. The sensitivity and specificity of pelvic examination for the detection of symptomatic ovarian cancer are not well established, but are poor and do not support physical examination as a screening method. CA 125 has limited sensitivity and specificity (ie, while CA 125 levels are increased in many women with ovarian cancer, only approximately one-half of early ovarian cancers produce enough CA 125 to cause a positive test, and noncancerous diseases of the ovaries and other cancers, as well as other noncancerous influences, also can increase the blood levels of CA 125).45-47 TVU is capable of detecting small ovarian masses and may distinguish some benign masses from some malignant adnexal masses, although it still only poorly predicts which masses are cancers and which are due to benign diseases of the ovary. As an independent test, ultrasound has shown poor performance in the detection of ovarian cancer in women at average or high risk.48 There have been research and attempts to develop a blood test for ovarian cancer based on measuring genes, proteins, or multiple marker assays that may be present in higher or lower amounts in women with ovarian cancer compared with women who do not have ovarian cancer. This is a relatively new area of investigation that is accumulating promising results, but still requires prospective studies for validation.49 Thus, at this time, the lack of supporting evidence indicating that any one or a combination of these strategies is efficacious has prevented recommendations for ovarian cancer screening, although several prospective randomized trials have been underway.
Two large, prospective, randomized trials, one in the United States and the other in the United Kingdom, have been studying screening average-risk women with a combination of CA 125 and TVU. The US trial, the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial,50 reported results in 2011.51 In the PLCO trial, 78,216 women ages 55 to 74 years were randomized to a group that was offered 6 annual rounds of screening with CA 125, and TVU for 4 years (n = 39,105) or a group that received usual care (n = 39,111). Participants were followed for a maximum of 13 years, with mortality from ovarian cancer as the main study outcome. At the conclusion of the study, the number of deaths from ovarian cancer was similar in each group (ie, there were 3.1 ovarian cancer deaths per 10,000 women-years in the group invited to screening vs 2.6 deaths per 10,000 women-years in the control group [relative risk, 1.18; 95% confidence interval, 0.82-1.71]). The authors concluded that simultaneous screening with CA 125 and TVU was not associated with a reduction in ovarian cancer mortality compared with usual care.51 However, the authors also noted that the absence of a stage shift in the group invited to screening compared with the control group suggests that the screening protocol in the PLCO study may not have been sensitive enough to diagnose ovarian cancer sufficiently early to alter its natural history. Nonetheless, for each of the 2 tests under evaluation, lower cutoff values would result in higher false-positive rates. An alternative approach, which is currently under evaluation in the UK Collaborative Trial of Ovarian Cancer Screening, is assessing the efficacy of multimodal screening including annual CA 125 screening with a risk of ovarian cancer algorithm and TVU as a second-line test versus annual screening with TVU only.52 The risk of ovarian cancer algorithm measures changes in CA 125 over time rather than with a single cutoff point, and is believed to improve sensitivity for smaller tumors without measurably increasing the false-positive rate.
While no organization recommends screening average-risk women for ovarian cancer, in 1994, a National Institutes of Health Consensus Panel concluded that women with 2 or more first-degree relatives diagnosed with ovarian cancer should be offered counseling about their ovarian cancer risk by a gynecologic oncologist (or another specialist qualified to evaluate family history and discuss hereditary cancer risks) since these women have a 3% chance of being positive for an ovarian cancer hereditary syndrome.53 The panel further advised that women with a known hereditary ovarian cancer syndrome, such as mutations on BRCA1 and BRCA2 (including breast-ovarian cancer syndrome, site-specific ovarian cancer syndrome, and (Lynch Syndrome) HNPCC), should receive annual rectovaginal pelvic examinations, CA 125 determinations, and TVU until childbearing is completed or at least until age 35 years, at which time prophylactic bilateral oophorectomy is recommended. Although women with these hereditary syndromes are estimated to represent only 0.05% of the female population, they have a 40% estimated lifetime risk of ovarian cancer." (Blogger's Note: the 40% would depend on which mutation)
open access: Cancer risks associated with external radiation from diagnostic imaging procedures - 2012 - CA: A Cancer Journal for Clinicians
Cancer risks associated with external radiation from diagnostic imaging procedures - 2012 - CA: A Cancer Journal for Clinicians
abstract: Laparoscopic and laparotomic staging in stage I epithelial ovarian cancer: a comparison of feasibility and safety - oncologic safety
Laparoscopic and laparotomic staging in stage I epithelial ovarian cancer: a comparison of feasibility and safety:
The aim of this study was to compare laparoscopic and laparotomic surgical staging in patients with stage I epithelial ovarian cancer in terms of feasibility and safety. A retrospective chart review was undertaken of all patients with apparent stage I epithelial ovarian cancer who underwent laparoscopic (laparoscopy group) or laparotomic (laparotomy group) surgical staging at the Center for Uterine Cancer, National Cancer Center, Korea, between January 2001 and August 2006. During the study period, 19 patients underwent laparotomic surgical staging and 17 patients underwent laparoscopic surgical staging. No cases were converted from laparoscopy to laparotomy. The two groups were similar in terms of age, body mass index, procedures performed, number of lymph nodes retrieved, and operating time. The laparoscopy group had less estimated blood loss (P = 0.001), faster return of bowel movement (P < 0.001), and a shorter postoperative hospital stay (P = 0.002) compared to the laparotomy group. Transfusions were required only in two laparotomy patients, and postoperative complications occurred only in four laparotomy patients. However, two patients with stage IA grade 1 and 2 disease in laparoscopy group had recurrence with one patient dying of disease. The accuracy and adequacy of laparoscopic surgical staging were comparable to laparotomic approach, and the surgical outcomes were more favorable than laparotomic approach. However, the oncologic safety of laparoscopic staging was not certain. This is the first report on the possible hazards of laparoscopic staging in early-stage ovarian cancer. In the absence of a large prospective trial, this technique should be performed cautiously.
abstract: Prognostic factors associated with response in platinum retreatment of platinum-resistant ovarian cancer
Prognostic factors associated with response in platinum retreatment of platinum-resistant ovarian cancer:
The goal of this study was to determine the factors associated with response to platinum retreatment in patients with platinum-resistant ovarian cancer. A review of patients with epithelial ovarian cancer retreated with cisplatin or carboplatin between 2002 and 2004 was performed. The platinum-free interval (PFI) and treatment-free interval (TFI) were determined for each patient. Response was based on serial CA125 levels using a modification of the Rustin criteria. Patients with clinical benefit ([CB] those who attained at least stable disease) were compared to patients with disease progression (PD). An analysis was performed to determine factors associated with CB in platinum-resistant patients retreated with platinum. Of 48 patients identified, 37 were evaluable included in this analysis. CB was observed in 27 (73%) while disease progression was noted in 10 (27%) women. The PFI was longer in those women who achieved CB (12.3 vs 6.9 months; P = 0.02). The TFI was 7.1 months for patients benefited from platinum retreatment vs 3.5 months for those with disease progression (P = 0.06). There was no statistically significant difference in the number of cytotoxic agents between the time of platinum retreatment and the prior platinum regimen (2 vs 1.5 months; P = 0.61). A prolonged PFI was associated with an improved chance of achieving CB with platinum retreatment. There was no association between the response to platinum retreatment and the number of intervening cytotoxic agents utilized. Further prospective study is warranted to define the optimal timing of platinum retreatment.
Long-term adjustment of early-stage ovarian cancer survivors:
The objectives of this study were to describe the quality of life (QOL), consequences of treatment, complementary therapy use, and factors correlating with psychologic state in 58 survivors of early-stage ovarian cancer since little is known about the QOL of early-stage ovarian cancer survivors. Survivors were interviewed using standardized measures to assess physical, psychologic, social, and sexual functioning; impact of cancer on socioeconomic status; and complementary therapy use. Survivors reported good physical QOL scores and few unmet needs. However, menopausal symptoms and negative impact on sexuality were reported. Less than 10% of survivors reported either an interest in sex or were sexually active. Psychologic assessment yielded a subset of 26% of patients with scores suggestive of posttraumatic stress disorder (PTSD) and 40% of survivors scored below the norm on the Mental Health Inventory-17 Survey. One third of patients required treatment for family/personal problems and took antianxiety medications. About 56% of survivors reported fear of cancer recurrence and 59% reported anxiety when their CA125 is tested. Better mental health was significantly related to less fatigue (Functional Assessment of Cancer Therapy [FACT]—fatigue, r = 0.61, P < 0.0001), less pain (European Organisation for Research and Treatment of Cancer [EORTC], r =−0.54, P < 0.0001), fewer stressful life events (Life Event Scale, r =−0.44, P > 0.001), and greater social support (MOS Social Support Survey, r = 0.41, P < 0.01). Early-stage ovarian cancer survivors had few physical complaints and unmet needs, but psychologic distress was evident in a subset of survivors; the majority of survivors reported sexual dysfunction. These results indicate the need for intervention and improved distress screening in the early-stage ovarian cancer population.
Common patterns in 558 diagnostic radiology errors:
Introduction: As a Quality Improvement initiative our department has held regular discrepancy meetings since 2003. We performed a retrospective analysis of the cases presented and identified the most common pattern of error.
Methods: A total of 558 cases were referred for discussion over 92 months, and errors were classified as perceptual or interpretative. The most common patterns of error for each imaging modality were analysed, and the misses were scored by consensus as subtle or non-subtle.
Results: Of 558 diagnostic errors, 447 (80%) were perceptual and 111 (20%) were interpretative errors. Plain radiography and computed tomography (CT) scans were the most frequent imaging modalities accounting for 246 (44%) and 241 (43%) of the total number of errors, respectively. In the plain radiography group 120 (49%) of the errors occurred in chest X-ray reports with perceptual miss of a lung nodule occurring in 40% of this subgroup. In the axial and appendicular skeleton missed fractures occurred most frequently, and metastatic bone disease was overlooked in 12 of 50 plain X-rays of the pelvis or spine. The majority of errors within the CT group were in reports of body scans with the commonest perceptual errors identified including 16 missed significant bone lesions, 14 cases of thromboembolic disease and 14 gastrointestinal tumours. Of the 558 errors, 312 (56%) were considered subtle and 246 (44%) non-subtle.
Conclusion: Diagnostic errors are not uncommon and are most frequently perceptual in nature. Identification of the most common patterns of error has the potential to improve the quality of reporting by improving the search behaviour of radiologists.
Review of epidemiologic studies of dietary acrylamide intake and the risk of cancer.:
Eur J Cancer Prev. 2012 Apr 8;
Hypothesized associations between dietary acrylamide intake and cancer have been evaluated in more than 15 epidemiologic studies examining almost every major cancer site. We have critically reviewed the epidemiologic studies of estimated dietary acrylamide exposure and cancer.....
In conclusion, epidemiologic studies of dietary acrylamide intake have failed to demonstrate an increased risk of cancer. In fact, the sporadically and slightly increased and decreased risk ratios reported in more than two dozen papers examined in this review strongly suggest the pattern one would expect to find for a true null association over the course of a series of trials. Therefore, continued epidemiologic investigation of acrylamide and cancer risk appears to be a misguided research priority.
Blogger's Note: the original paper and editorial were recently posted, however, the Medpage (Medscape) article is easier to read (eg. plain english)
DNA Repair Genes May Predict Ovarian Cancer Survival - in Oncology/Hematology, Ovarian Cancer from MedPage Today
"A high score based on the expression of 23 genes involved in repairing DNA damage after platinum-based chemotherapy for ovarian cancer was associated with a 5-year survival of 40% versus 17% for women who had a low score, investigators reported......"
Climb4Life Documentary Coming to Denver | HERA Women's Cancer Foundation - honoring (the late) Sean Patrick founder HERA
Climb4Life Documentary Coming to Denver | HERA Women's Cancer Foundation
Climb4Life Documentary Coming to Denver
April 12, 2012The new KUED PBS documentary on HERA’s founder, Sean Patrick, recently premiered in Salt Lake City to a very enthusiastic audience.
Now, “Climb for Life: A Legacy” is coming to Denver! Please join us for this special showing as we celebrate Sean’s life and work. In establishing the HERA Women’s Cancer Foundation, she gathered a community, became a catalyst for change, and continues, even after her death, to inspire the critical quest for ovarian cancer research and awareness.
Saturday, May 5, 2012, 7:00-9:00 pm
at The Garden, 3435 Albion Street, Denver, CO 80207; 303-321-5231
Higher US expenditures on cancer patients do not result in improved mortality. : denialism blog
Blogger: Hoofnagle has a MD and PhD in physiology from the University of Virginia, and is now a general surgery resident. His interest in denialism concerns the use of denialist tactics to confuse public understanding of scientific knowledge.
Higher US expenditures on cancer patients do not result in improved mortality.
" But you'd never know that reading AEI's highly dubious contribution to the literature in this week's Health Affairs (lay Reuters article here). Consistent with their free-market solves everything and can do no wrong (cover ears and yell "nananananananana") attitude towards the broken US healthcare system, they have managed to contaminate the literature with a paper that suggests our higher expenditures on cancer are generating significant returns in patient survival. Except that it doesn't show this, and to her great credit, Reuter's Sharon Begley nails it:........
"Experts shown an advance copy of the paper by Reuters argued that the tricky statistics of cancer outcomes tripped up the authors.
"This study is pure folly," said biostatistician Dr. Don Berry of MD Anderson Cancer Center in Houston. "It's completely misguided and it's dangerous. Not only are the authors' analyses flawed but their conclusions are also wrong."
".... It's been a topic of debate among medical professions and discussed extensively by other medical bloggers like Ora.....(Blogger's Note: see prior postings)
Fecal occult blood testing instructions and impact on patient adherence: Publication year: 2012
Source: Cancer Epidemiology
Although the physician's role with patients is crucial in encouraging FOBT screening, the nature and content of physician-patient discussions about FOBT screening is unclear. As part of a larger study, this paper reports on our analyses of physician beliefs about fecal occult blood testing (FOBT) and strategies they employed to enhance patient adherence. The second aim of this paper is to report on the perceptions of individuals at average risk for colorectal cancer (CRC) in regard to their awareness of the FOBT and their responses to physician recommendations about FOBT screening.
Clinical value of 18F-FDG PET-CT in detecting primary tumor for patients with carcinoma of unknown primary
Clinical value of 18F-FDG PET-CT in detecting primary tumor for patients with carcinoma of unknown primary: Publication year: 2012
To investigate the clinical value in detecting occult primary tumors with 18F-FDG PET-CT whole body imaging.
120 patients with unknown primary origin were referred for 18F-FDG PET-CT whole body imaging. All patients were performed 18F-FDG PET-CT whole body scan. PET-CT images were interpreted by visual inspection and semi-quantitative analysis (standardized uptake value, SUV). Histopathological and formal clinical follow-up findings were used to assess the value of FDG PET-CT.
FDG PET-CT was able to detect the primary tumor in 54/120 patients (42.5%). The primary tumors were confirmed by histopathologic and formal clinical follow-up findings, and located in the head and neck (n =17), the lung (n =19), the breast (n =2), the esophagus (n =1), the stomach (n =2), the bile ducts (n =1), the pancreas (n =3), the co1on (n =3), the ovary (n =2), the prostate (n =l), others (n =3). FDG PET results were proved false positive in 9 patients (7.5%), which were located in the head and neck (n =3), the lung (n =1), the gastric (n =1), the colon (n =2), the ovary (n =1), the prostate (n =l).
During the clinical follow-up of median 32months (range, 2–45months), primary tumor was found in only 5 patients of 60 cases unidentified by PET-CT (breast cancer, gastric cancer, co1on cancer, prostate cancer and urinary tumors, respectively). The sensitivity, specificity, and accuracy of 18F-FDG PET-CT in the detection of the primary tumor site were 91.5%, 85.2%, and 88.3%, respectively.
18F-FDG PET-CT whole body imaging is both a noninvasive and a very sensitive tomographic whole-body imaging modality, allowing for the detection of a primary tumor and complete tumor staging in single examination, which can contribute substantially to selecting appropriate therapeutic methods and evaluating prognosis. Perhaps 18F-FDG PET-CT whole body imaging should be used as a first-line imaging modality for patients with carcinoma of unknown primary rather than using it after other diagnostic procedures have failed to identify a primary tumor.
abstract - Patient Education and Counseling - Teaching patients how to talk with biomedical providers about their complementary and alternative medicine use
Patient Education and Counseling - Teaching patients how to talk with biomedical providers about their complementary and alternative medicine use
open access: Gynecologic Oncology Case Reports - A case of endometrial cancer in the context of a BRCA2 mutation and double heterozygosity for Lynch syndrome
ScienceDirect.com - Gynecologic Oncology Case Reports - A case of endometrial cancer in the context of a BRCA2 mutation and double heterozygosity for Lynch syndrome
"....While endometrial cancer diagnosed under the age of 50 is not included in the Revised Bethesda Guideline, evidence suggests that these individuals should be evaluated for Lynch syndrome (Resnick et al., 2009). The patient presented was diagnosed with endometrial cancer at the age of 41 and genetic testing revealed triple heterozygosity for BRCA2, MLH1 and MSH6 mutations."
Lynch syndrome, also called hereditary non-polyposis colorectal cancer (HNPCC), is an autosomal dominant cancer susceptibility syndrome caused by germline mutations in DNA mismatch repair (MMR) genes, MLH1, MSH2, and less frequently MSH6 and PMS2. MMR mutation carriers are predisposed primarily to colorectal cancer and endometrial cancer, with an increased frequency of stomach, ovary, pancreas, upper urinary tract, brain, small bowel, and skin consistently reported. This hereditary syndrome accounts for approximately 2–3% of colorectal cancers and 1–4% of endometrial cancers in the United States (Lynch and de la Chapelle, 2003). Depending on the MMR gene involved, women with Lynch syndrome can have up to an 80% lifetime risk of developing colorectal cancer, and a 20–60% risk of endometrial cancer.
Germline mutations in BRCA1 or BRCA2 (BRCA1/2) cause hereditary breast ovarian cancer syndrome. Female carriers of BRCA1/2 mutations have excessive risks for both breast and ovarian cancer, with lifetime breast cancer estimates ranging from 45% to 84%, and lifetime ovarian cancer estimates ranging from 11% to 62%, depending upon the population studied. BRCA1/2 kindreds are also noted to have an increased frequency of prostate cancer, and in BRCA2 kindreds, increased frequencies of pancreatic cancer and melanoma are observed. The frequency of BRCA1 or BRCA2 mutations in the general population is estimated to be 1 in 300 to 1 in 800, respectively (King et al., 2003).
► Endometrial cancer with BRCA2 mutation and double heterozygosity for Lynch syndrome.
► Loss of MLH1 and PMS2 by immunohistochemical stain.
► MSH1 and MSH6 gene mutations by genomic sequencing.
► Loss of MLH1 and PMS2 by immunohistochemical stain.
► MSH1 and MSH6 gene mutations by genomic sequencing.
abstract: Comparative cost efficiency across the European G5 countries of originators and a biosimilar erythropoiesis-stimulating agent to manage chemotherapy-induced anemia in patients with cancer
Comparative cost efficiency across the European G5 countries of originators and a biosimilar erythropoiesis-stimulating agent to manage chemotherapy-induced anemia in patients with cancer
Conclusion: Managing chemotherapy-induced anemia with biosimilar epoetin α is consistently cost efficient over treatment with originator epoetin α, epoetin β, and darbepoetin α under both fixed and weight-based dosing scenarios.
Friday, April 13, 2012
Epigenetics does not mean that thinking makes it so : Respectful Insolence
".....The not-so-subtle implication is that the reason one gets sick is because of one's habits. Of course, there are a lot of lifestyle diseases, but the implications goes beyond the sensible, science-based observation that obesity and lack of exercise increase the risk of certain diseases, into the realm of stating that if you just eat the right foods and do the right exercises you'll never get sick.
Utter nonsense, of course.
There's also a dark side to this sort of thinking, and that's the flip side of the argument. If you can nearly completely control the state of your health by what you eat and do, the not-so-subtle implication is that if you get sick it must be your fault. After all, if we have complete control over our health through our lifestyle, then it follows that if you're sick, you must be doing something wrong....."
"The latest way that quacks are trying to push the idea that you have near total control over your health is by abusing new findings in epigenetics. Epigenetics is the study of heritable changes in gene expression or phenotype that are not caused by changes in the underlying gene sequence........ It's a fascinating area of research, because it suggests that gene expression can be altered longer than transiently by environmental influences. Of course, given that organisms and biology are affected by environmental influences, this is almost a trivial observation; the power of epigenetics is that it can explain how such changes in gene expression can come about.....
Ginkgo May Sensitize Ovarian Cancer Cells to Cisplatin: Antiproliferative and Apoptosis-Inducing Effects of Ginkgolide B on Ovarian Cancer Cells
Ginkgo May Sensitize Ovarian Cancer Cells to Cisplatin: Antiproliferative and Apoptosis-Inducing Effects of Ginkgolide B on Ovarian Cancer Cells:
Ginkgolide B (GB), the primary active component of Ginkgo biloba extracts, may have antitumor properties. The objective of this study was to determine the effects and possible mechanisms of GB in ovarian cancer cells. In this study, human ovarian cancer cell lines (SKOV3 and CAOV3) were treated with different concentrations of GB alone or in combination with Cis-diaminodichloroplatinum (CDDP). .......Furthermore, GB had significantly less cytotoxicity than CDDP in normal human ovarian surface epithelial cells. This study suggests that GB can be proposed as an effective antiproliferative and apoptosis-inducing agent with interesting translational application in ovarian cancers, used in addition to conventional chemotherapy.
The transcription factor FOXL2: At the crossroads of ovarian physiology and pathology: Publication year: 2012
Source:Molecular and Cellular Endocrinology
FOXL2 is a gene encoding a forkhead transcription factor. Its mutations or misregulation have been shown to cause the blepharophimosis–ptosis–epicanthus inversus (BPES) syndrome and more recently have been associated with the development of Ovarian Granulosa Cell Tumors (OGCT). BPES is a genetic disorder involving mild craniofacial abnormalities often associated with premature ovarian failure. OGCTs are endocrine malignancies, accounting for 2–5% of ovarian cancers, the treatment of which is still challenging.
In this review we summarize recent data concerning FOXL2 transcriptional targets and molecular partners, its post-translational modifications, its mutations and its involvement in newly discovered pathophysiological processes. In the ovary, FOXL2 is involved in the regulation of cholesterol and steroid metabolism, apoptosis, reactive oxygen species detoxification and cell proliferation. Interestingly, one of the main roles of FOXL2 is also to preserve the identity of ovarian granulosa cells even at the adult stage and to prevent their transdifferentiation into Sertoli-like cells. All these recent advances indicate that FOXL2 is central to ovarian development and maintenance. The elucidation of the impact of FOXL2 germinal and somatic mutations will allow a better understanding of the pathogenesis of BPES and of OGCTs.
Foundation for Women’s Cancer Announces 2011-2012 Research Grant Awardees - Press Release - Digital Journal
Foundation for Women’s Cancer Announces 2011-2012 Research Grant Awardees - Press Release - Digital Journal
Florence and Marshall Schwid Ovarian Cancer Research Grant: Petar Jelinic, PhD, Sloan Kettering Institute for Cancer Research
open access: Editorial: Molecular Scores to Predict Ovarian Cancer Outcomes: A Worthy Goal, but Not Ready for Prime Time
Molecular Scores to Predict Ovarian Cancer Outcomes: A Worthy Goal, but Not Ready for Prime Time
"... The premature application of inadequately validated biomarkers may adversely impact the successful implementation of individualized therapies."
open access: A DNA Repair Pathway–Focused Score for Prediction of Outcomes in Ovarian Cancer Treated With Platinum-Based Chemotherapy (serous)
A DNA Repair Pathway–Focused Score for Prediction of Outcomes in Ovarian Cancer Treated With Platinum-Based Chemotherapy
Patient SamplesWe extracted clinical data for 511 patients with serous ovarian cystadenocarcinoma from The Cancer Genome Atlas (TCGA) database (44) website (http://tcga-data.nci.nih.gov) on February 17, 2011, representing the largest available dataset of epithelial ovarian cancer gene expression profiles (see Supplementary Table 2, available online, for further details on which ovarian cancer samples were included in this study). These were all the patients for whom full sets of tumor gene expression data were available for download.....
Clinicopathologic characteristics of ovarian cancer patients in The Cancer Genome Atlas (TCGA) dataset*
Genes in platinum-specific DNA repair pathways that were used to construct the score*
(For each gene, “high” means higher than median gene expression was associated with improved overall survival in The Cancer Genome Atlas dataset, and “low” means higher than median gene expression was associated with worse overall survival
CONTEXT AND CAVEATS
At present, there are no effective prognostic tools for prediction of response in ovarian cancer patients, a majority of whom are diagnosed with an advanced stage (stages III and IV) and undergo surgical debulking followed by and platinum-based chemotherapy.
Gene expression data was extracted from The Cancer Genome Atlas (TCGA) database for patients with advanced ovarian cancer, and a molecular score was developed by focusing exclusively on the genes involved in platinum-induced DNA damage repair pathways. Patients were divided into low (0–10) and high (11–20) scores, and the prognostic value of the score for overall survival, recurrence-free survival, and progression-free survival was assessed. Data were validated in two independent datasets.
Patients with high scores showed statistically significant associations with improved overall survival compared with patients with low scores. The score was predictive of overall survival, recurrence-free survival, and progression-free survival in ovarian cancer patients who received first-line platinum-based chemotherapy.
This score has the potential to become an important prognostic tool to determine whether advanced-stage ovarian cancer patients will benefit from first-line platinum-based chemotherapy.
The score has not been tested prospectively in a clinical trial.
20 Great Challenges: Votes are in! | TEDMED Blog
Jay Walker just announced the results of voting on the 20 Great Challenges of health and medicine. The program, sponsored by the Robert Wood Johnson Foundation, looks at the most persistent and complex issues facing health and medicine today.
The Top 20 Great Challenges:
#22. Inventing Wellness Programs
#34. The Caregiver Crisis
#19. The Role of the Patient
#2. The Obesity Crisis
#1. Achieving Medical Innovation
#8. Managing Chronic Diseases
#18. Medical Communication
#26. Reducing Childhood Obesity
#3. Making Prevention Popular
#9. End-of-life Care
#51. Causes of Sleep Deprivation
#15. Impact of Poverty on Health
#12. Faster Adoption of Best Practices
#32. Impact of Stress
#4. Future of Personalized Medicine
#33. Promoting Active Lifestyles
#10. Preparing for Dementia
#16. Addressing Healthcare Costs
#39. Whole-Patient Care#23. Eliminating Medical Errors
Throughout the year, the Great Challenges Program will generate a lively national dialog on the 20 Challenges chosen by the TEDMED community. The program will include TV-style interviews with leaders across fields, a series of webinars on each of the 20 Great Challenges, and the opportunity for TEDMED community members to add their voice.
Thursday, April 12, 2012
abstract: Validating the Impact of a Molecular Subtype in Ovarian Cancer on Outcomes – A Study of the OVCAD Consortium - Pils - Cancer Science - Wiley Online Library
Validating the Impact of a Molecular Subtype in Ovarian Cancer on Outcomes – A Study of the OVCAD Consortium - Pils - Cancer Science -
The majority of patients with epithelial ovarian cancer (EOC) is diagnosed at advanced stage and has a poor prognosis. A small proportion of these patients though will survive while others die very quickly. Clinicopathological factors do not allow precise identification of these subgroups. Thus we have validated a molecular subclassification as new prognostic factor in EOC.
One hundred ninety-four patients with stage II to IV EOC were characterized by whole-genome expression profiling of tumor tissues and classified using a published 112 gene-set, derived from a FIGO stage directed supervised classification approach.
The 194 tumor samples were classified into two subclasses of 95 (subclass 1) and 99 (subclass 2) tumors, grouping all 9 FIGO II tumors in subclass 1 (p=0.001). Subclass 2 (54% of advanced stage tumors) correlated significantly with peritoneal carcinomatosis and non-optimal debulking. Patients with subclass 2 tumors had a worse overall survival in both histological subtypes both, univariate (HRs 3.17 (serous) and 17.11 (non-serous), p≤0.001) and in models corrected for relevant clinicopathologic parameters (HRs 2.87 (serous) and 12.42 (non-serous), p≤0.023). Significance analysis of microarrays revealed 2,082 genes differentially expressed in advanced grade serous tumors of both subclasses and the focal adhesion pathway as the most deregulated pathway.
In this validation study we showed that in advanced-stage serous ovarian cancer two approximately equally large molecular subtypes exist, independent from classical clinocopathological parameters presenting with highly different whole genome expression profiles and an impressively different overall survival. Similar results were obtained in a small cohort of patients with non-serous tumors.
Does Estrogen-Only HRT Decrease Breast Cancer Risk? Nationally Recognized Endocrinologist Dr. Marina Johnson Weighs In
Does Estrogen-Only HRT Decrease Breast Cancer Risk? Nationally Recognized Endocrinologist Dr. Marina Johnson Weighs In
"....So here's Dr. Johnson's take-home message: "You don't need to delay starting HRT if you choose natural estradiol and progesterone over synthetic estrogens and progestins. Don't endure symptoms like hot flashes, insomnia, anxiety, depression, sexual dysfunction, mental confusion, and weight gain. Start HRT within 10 years of menopause for the most protection against Heart Disease, Alzheimer's and Osteoporosis.
"Avoid the increased heart attacks and strokes seen in WHI by choosing topical estrogen in the form of patches, gels, creams and mists that are available at any drug store. Pharmaceutical natural hormones (also called bioidentical hormones) are superior to compounded bioidentical hormones because they are required to meet higher standards for quality control and efficacy."
Read more in Dr. Johnson's book, "Outliving Your Ovaries: An Endocrinologist Weighs The Risks And Rewards Of Treating Menopause With Hormone Replacement Therapy" (http://www.outlivingyourovaries.com) (Eyesong Publishing, February 2011), which is available in paperback, e-book and can be shipped internationally. Use coupon code BZCWJDM5 for $5 off of the retail price with purchase at http://www.buydrmarinajohnsonbook.com.
Dr. Marina Johnson, a pharmacist and UCLA/USC-trained physician, is board-certified in Endocrinology and Internal Medicine.
Current Drug Shortages: Etoposide solution for injection (updated):
Bedford Laboratories has 100mg/5ml available in limited quantities. Once this supply is depleted, the next estimated release dates are unknown. All other presentations are out os stock and the company cannot estimate a release date. Production is pending as capacity permits. Availability of products is updated on the Bedford Laboratories website. Etoposide Injection 20 mg/mL; 5 mL; 53776 vials in stock; approximately 45000 vials will be in warehouse by the 3rd week of this month.
CMAJ: Young women with breast cancer genes face tough choices (8th part of a series in genetic testing - see links)
CMAJ: Young women with breast cancer genes face tough choices
Editor’s note: Eighth of a multipart series on genetic testing.
Part 1: Separating hype from reality in the era of the affordable genome (www.cmaj.ca/lookup/doi/10.1503/cmaj.109-4143).
Part 2: Popping the genetics bubble (www.cmaj.ca/lookup/doi/10.1503/cmaj.109-4142).
Part 3: Who should hold the keys to your DNA? (www.cmaj.ca/lookup/doi/10.1503/cmaj.109-4141).
Part 4: A race-based detour to personalized medicine (www.cmaj.ca/lookup/doi/10.1503/cmaj.109-4133).
Part 5: Race and genetics in the doctor’s office (www.cmaj.ca/lookup/doi/10.1503/cmaj.109-4134).
Part 6: Predisposed to risk but not change (www.cmaj.ca/lookup/doi/10.1503/cmaj.109-4157).
Part 7: Unhealthy behaviours influenced by genes and environment (www.cmaj.ca/lookup/doi/10.1503/cmaj.109-4162).
abstract: Shorter telomere length is associated with increased ovarian cancer risk in both familial and sporadic cases.
Shorter telomere length is associated with increased ovarian cancer risk in both familial and sporadic cases.:
J Med Genet. 2012 Apr 6;
Alterations in telomere maintenance mechanisms leading to short telomeres underlie different genetic disorders of ageing and cancer predisposition syndromes. It is known that short telomeres and subsequent genomic instability contribute to malignant transformation, and it is therefore likely that people with shorter telomeres are at higher risk for different types of cancer. Recently, the authors demonstrated that the genes BRCA1 and BRCA2 are modifiers of telomere length (TL) in familial breast cancer. The present study analysed TL in peripheral blood leucocytes of hereditary and sporadic ovarian cancer cases, as well as in female controls, to evaluate whether TL contributes to ovarian cancer risk.
TL was measured by quantitative PCR in 178 sporadic and 168 hereditary ovarian cases (46 BRCA1, 12 BRCA2, and 110 BRCAX) and compared to TL in 267 controls.
Both sporadic and hereditary cases showed significantly shorter age adjusted TLs than controls. Unconditional logistic regression analysis revealed an association between TL and ovarian cancer risk with a significant interaction with age (p<0.001). Risk was higher in younger women and progressively decreased with age, with the highest OR observed in women under 30 years of age.
These findings indicate that TL could be a risk factor for early onset ovarian cancer.
abstract: Assumptions of Expected Benefits in Randomized Phase III Trials Evaluating Systemic Treatments for Cancer
Assumptions of Expected Benefits in Randomized Phase III Trials Evaluating Systemic Treatments for Cancer
Background In designing phase III randomized clinical trials (RCTs), the expected magnitude of the benefit of the experimental therapy (δ) determines the number of patients required and the number of person-years of follow-up. We conducted a systematic review to evaluate how reliably δ approximates the observed benefit (B) in RCTs that evaluated cancer treatment.
Conclusions Investigators consistently make overly optimistic assumptions regarding treatment benefits when designing RCTs. Attempts to reduce the number of negative RCTs should focus on more realistic estimations of δ. Increased use of interim analyses, certain adaptive trial designs, and better biological characterization of patients are potential ways of mitigating this problem.
Stem Cell Network Blog: 35 reasons to like stem cells - images and art/voting open on FB "Cells I See"
Blogger's Note: the FB art/images are fabulous - take a look/vote if you wish
Stem Cell Network Blog: 35 reasons to like stem cells
April 12, 2012
35 reasons to like stem cellsby Lisa Willemse
Cells I See. You may have viewed announcements of the winners in previous blog posts. The contest, by and large, was a quiet affair, known only to a few who weren't part of the Network's annual scientific conference -- where the entries were displayed and conference attendees selected the winner via blind judging.
We were content to keep it this way, until we realized that we were, in essence, hiding some of the most incredible stem cell images we've ever seen. Prompted by interest from the Ontario Science Centre, we installed a small exhibit in their museum and the response was incredible. Most people had no idea what stem cells looked like and were amazed at their beauty and complexity. The overriding message was that people are interested not just in the science of stem cells, but in stem cell images and art.
In response, Cells I See has gone social -- we've opened up the 2012 voting to the world. Anyone with a Facebook profile can participate by "liking" any of the 35 entries in this year's contest. Of course, we invite you to share it with your friends and colleagues as well -- the images are breathtaking, displaying a range of cell types, colours and patterns.
But don't take my word for it, go see them for yourself.
abstract: Preoperative assessment of peritoneal carcinomatosis: intraindividual comparison of 18F-FDG PET/CT and MRI
Preoperative assessment of peritoneal carcinomatosis: intraindividual comparison of 18F-FDG PET/CT and MRI:
With high diagnostic accuracy for PC of both, MRI and PET/CT, PET/CT provides better diagnostic accuracy and especially better NPV.
open access: A Pilot study of the Sharing Risk Information Tool (ShaRIT) for Families with Hereditary Breast and Ovarian Cancer Syndrome - study of 19 BRCA carriers
A Pilot study of the Sharing Risk Information Tool (ShaRIT) for Families with Hereditary Breast and Ovarian Cancer Syndrome
".....ShaRIT strives to ease the “burden of the messenger” and decrease the possibility of mis-communicating and misinterpreting
important medical information to their relatives."
Wednesday, April 11, 2012
Current Drug Shortages: Ondansetron Injection 2 mg/mL (updated):
Apotex has discontinued the manufacturing of Ondansetron Injection.
Oncologists Are Not Health Economists, Suggests Survey
"Interestingly, responses to the clinical scenario did not significantly differ between American and Canadian oncologist."
Faults seen in cancer study funding | Reuters
NEW YORK | Wed Apr 11, 2012 11:08am EDT(Reuters Health) - It's well-known that clinical trials of cancer treatments often can't cover their costs. But a new study suggests that government-funded trials could take at least one cue from those backed by drug companies.
In 2010, the Institute of Medicine (IOM) released a report saying that the U.S. system for conducting cancer clinical trials was approaching a "state of crisis" (see Reuters story of April 10, 2010).
The IOM -- an expert panel with federal support -- said the National Cancer Institute's Clinical Trials Cooperative Group program was inefficient, bogged down by red tape and underfunded.
The NCI program includes a number of collaborative groups -- academic cancer centers, researchers and community doctors that work together to conduct trials on cancer treatment. Altogether, the program involves more than 3,100 institutions in the U.S., Canada and Europe.
In the new study, researchers at one Canadian cancer center focused specifically on the timing of cancer clinical trial funding.
With cooperative group trials, funding typically comes as a "modest payment up front" for each patient enrolled, explained lead researcher Dr. Hsien-Yeang Seow of McMaster University and the Juravinski Cancer Center in Hamilton, Ontario.
Trials done by the drug industry, on the other hand, dole out money over time, as patients hit certain "milestones" -- like during treatment, and as they come back for follow-up visits after treatment ends.
Seow's team looked at 97 clinical trials done at its center in recent years. Two-thirds of those studies were cooperative group trials, including some with NCI funding, while the rest were industry-sponsored.Those included early- and late-stage trials of treatments for cancers including breast, lung and stomach cancer.
The researchers found that the cooperative group trials quickly began to lose money after the initial stages because the funds were all spent early on. That leaves nothing for study patients' follow-up, which can last for years.
The industry trials, in contrast, had more money going in than out at multiple time points -- though any net income typically disappeared during longer term follow-up.
What's more, Seow's team found, its center had fallen into a pattern of starting new clinical trials in order to pay for patients' follow-up in the older, ongoing trials.
Seow likened it to a "Ponzi scheme" -- albeit an unintentional and legal variant.
"In order to stay afloat," Seow explained in an interview, "we have to start new trials and recruit new patients."
The money from that new-patient accrual then goes to "pay down the deficit" of earlier trials. "Obviously, that's not sustainable," Seow said.
One way to help with the larger issue of sustaining cooperative group trials could be to switch from "up front" payment, according to Seow.
The author of an editorial published with the study in the Journal of Clinical Oncology agrees. "Perhaps it is time to consider more closely following the pharmaceutical industry model of progress payments," writes Dr. David M. Dilts, of the Knight Cancer Institute in Portland, Oregon.
That, he adds, could help stop the "robbing Peter to pay Paul" habit of using new trials to fund old ones.
An alternative for individual cancer centers would be to take part in fewer and fewer cooperative group trials, and more industry-funded ones.
A recent survey of centers in the NCI cooperative program suggested that is happening: one-third said they were going to limit their participation in NCI-funded trials in the future.
But non-industry trials are vital, Seow pointed out. Drug company studies may bring us the "next blockbuster drug," he noted, but the cooperative group trials help answer the bigger questions of how to improve cancer patients' overall care.
This new analysis, Seow said, looks at just one aspect of the larger, complicated issue.
The 2010 report from the IOM recommended an overhaul of the NCI cooperative group program. Many of its suggestions focused on efficiency: the process of simply designing a trial, for example, is lengthy and cumbersome -- taking an average of two years to complete.
It also called for more funding. The NCI's payment-per-patient has not changed in a decade, standing at about $2,000. But the actual cost is thought to be closer to $6,000, Dilts points out in his editorial.
The NCI has said it plans to boost that reimbursement to $4,000, at least to "high performance" centers that enroll a large number of patients in clinical trials.
In an email to Reuters Health, a spokesperson for the organization said it recognizes the need for more funding going to individual study sites.
But centers may still end up spending the money up front, Dilts notes -- especially with today's trend of doing expensive genetic testing of patients. That's done because researchers are increasingly trying to develop treatments that are "personalized" to patients' genetic makeup.
So there still may be no money left over for years of patient follow-up.
Another option, Seow said, is to finally close some of the long-running "mega-trials" that are no longer generating useful information.
But the wider problem will ultimately need multiple solutions, according to Seow.
"There have been remarkable breakthroughs in cancer therapies," he said. "But there's a state of crisis in clinical trials right now, and there are many reasons for it."
SOURCE: bit.ly/GSkEGD Journal of Clinical Oncology, online March 26, 2012.