OVARIAN CANCER and US

Tuesday, April 12, 2016

OvarianCancerandUs blog - page views this week by country (top 10)

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Virtual cancer advisor to support patients (interesting) IBM Watson/ACS

magazine article

IBM Chairman and CEO Ginni Rometty announced IBM’s partnership with the American Cancer Society to create the first 'advisor' for people fighting cancer, powered by Watson cognitive computing, today, at the World Health Care Congress in Washington, DC. (John Boal/Feature Photo Service for IBM)

Bleeding Risks With Aspirin Use for Primary Prevention in Adults: A Systematic Review ++

Bleeding Risks With Aspirin Use for Primary Prevention in Adults: A Systematic Review for the U.S. Preventive Services Task ForceBleeding Risks With Aspirin Use | Annals of Internal Medicine

Limitations: Power to detect effects on hemorrhagic stroke was limited. Harms other than serious bleeding were not examined.
Conclusion: Consideration of the safety of primary prevention with aspirin requires an individualized assessment of aspirin's effects on bleeding risks and expected benefits because absolute bleeding risk may vary considerably by patient.

See Also:

USPSTF: Final Guidelines on Aspirin as CVD, Cancer Prevention

Aspirin

Canada (media video): Did federal (Trudeau/Liberals) budget come up short for health care? | Watch News Videos Online

News Videos Online

Methods Used in Economic Evaluations of Testing and Diagnosis for Ovarian Cancer: A Systematic Review

abstract

Objective: There are multiple tests available that can help diagnose ovarian cancer, and the cost-effective analysis of these diagnostic interventions is essential for making well-informed decisions regarding resource allocation. There are multiple factors that can impact on the conclusions drawn from economic evaluations including test accuracy, the impact of the testing pathway on patient costs and outcomes, and delays along the ovarian cancer test-treat pathway. The objective of this study was to evaluate how test accuracy, the choice of perspective, and delays along the testing and diagnostic pathway have been incorporated in economic evaluations of testing for ovarian cancer.

Methods: A systematic review of published literature was undertaken to identify economic evaluations (eg, cost-effectiveness, cost-utility analysis) focused on testing and diagnosis for ovarian cancer.

Results: Seven studies met the inclusion criteria. Six studies incorporated test accuracy and its impact on patients to some extent. Four studies adopted a societal perspective, but only one considered the costs incurred by patients on the testing and diagnosis pathway. Where delays on the testing pathway were incorporated into the analysis, these were frequently due to false-negative test results leading to delays in patients accessing treatment. Any anxiety that patients might experience as a result of a positive test was not considered in these studies.

Conclusions: The impact on patients of receiving a positive test in terms of anxiety and the costs incurred by patients having to attend for testing and diagnosis are rarely considered. Delays along the testing and diagnosis pathway can have a major effect on patient outcomes, and it is important that these are acknowledged in economic evaluations focused on testing. Future economic analysis should incorporate these key determinants in order that diagnostic tests for ovarian cancer can be robustly evaluated.

open access: Lynch syndrome mutation spectrum in New South Wales, Australia, including 55 novel mutations

open access

Abstract

Background

Lynch syndrome, the most frequent hereditary colorectal cancer syndrome, is caused by defects in mismatch repair genes. Genetic testing is important in order to identify mutation carriers who can benefit from intensive surveillance programs. One of the challenges with genetic testing is the interpretation of pathogenicity of detected DNA variants. The aim of this study was to investigate all putative pathogenic variants tested for at the Division of Molecular Medicine, Pathology North, in Newcastle, Australia, to establish whether previous variant classification is in accordance with that recently performed in the InSiGHT collaboration.

The aim of this study was to investigate all putative pathogenic variants tested for at the Division of Genetics, Hunter Area Pathology Service (HAPS), Pathology North, in Newcastle, New South Wales, Australia, to establish whether previous variant classification is in accordance with that performed in the InSiGHT collaboration.

This report is a follow‐up study from Scott et al. (2001) and from Talseth‐Palmer et al. (2010) which presented data from 32 (MLH1 or MSH2) and 35 (MSH6 or PMS2) mutation positive families, respectively. Here, we present data from 333 mutation positive families.

Methods

Prediction programs and available literature were used to classify new variants or variants without classification.

Results

We identified 333 mutation positive families, in which 211 different putative pathogenic mismatch repair mutations were found. Most variants with an InSiGHT classification (141 out of 146) were in accordance with our classification. Five variants were discordant, of which one can definitively be reclassified according to the InSiGHT scheme as class 5. Sixty‐four variants had not been classified by InSiGHT, of whom 55 have not been previously reported.

Conclusion

In conclusion, we found that our classifications were mostly in accordance with the InSiGHT scheme. In addition to already known MMR mutations, we have also presented 55 novel pathogenic or putative pathogenic mutations......

Editorial: Global reach: Promoting ethical best practices and the quality and integrity of medical publications worldwide - Current Medical Research and Opinion - Volume 32, Issue sup1

Editorial - open access:
Global reach: Promoting ethical best practices and the quality and integrity of medical publications worldwide - Current Medical Research and Opinion - Volume 32, Issue sup1

According to most measures of scientific output, the volume of citable scientific literature worldwide is increasing astronomically each year. It has been estimated that a new life science paper appears in print or online every minute or less. As most of us know, the amount of data generated from just a single clinical trial can be so extensive that much of it, when published, has to reside in online supplementary appendices, which can be many times longer than the primary publication, and key information may be lost in the vast expanse of supplementary figures, tables, and other material.

This raises a fundamental issue – how can we present this explosion of data in a way that people can understand it? At least one answer is through the application of interpretation. Technology allows us to make vast quantities of data widely available, but without context it is almost impossible for the end user to process. We need individuals who have the skills to change data from a (sometimes enormous) collection of facts to an understandable narrative and, conversely, we need to ensure that any narrative is more than just professional opinion or conjecture, but is backed up by evidence.

Monday, April 11, 2016

A 3-year study of high-cost users of health care (Ontario, Canada) + comparison to U.S. (for those of us who are 'high cost users'

Blogger's Note: (re: highlighted text below) for those following healthcare in Ontario = too late

cmaj - open access (pdf)
January 11, 2016

.....Health care spending per person in any given year is highly uneven. The concentration of health care utilization among small numbers of patients is well established. In the United States, the Agency for Healthcare Research and Quality reported that 1% of users in 2008 accounted for 20% of expenditures and that 5% of users accounted for nearly 50% of expenditures.1 Data from Canada in 1972 and 1996, and again in 2009, showed that high-cost users (individuals with the highest 5% of costs) consumed 65% of combined hospital and nursing home costs, 64% of acute care days and 84% of combined acute and post-acute home care resources, respectively.2–4.....

= too late:

....The Commission on the Reform of Ontario’s Public Services recommended efficiencies be found in health care for high-cost users in Ontario.12 Finding efficiencies does not necessitate reducing necessary care or total health care spending. Appropriate and high-value care must not be reduced or compromised. Results from our study suggest that causes and solutions vary by age. Results from randomized controlled trials of integrated care programs have had success primarily among high-risk older adults.13–16 But integrated care models are expensive and need to be targeted carefully to people who have utilization patterns that would benefit from coordination and integration over time, such as frail older patients with multiple chronic medical and functional impairments.

Canadian Medical Association Journal: Choosing Wisely Canada seeks system change

An integrated model of clinical information and gene expression for prediction of survival in ovarian cancer patients

Abstract

Accumulating evidence shows that clinical factors alone are not adequate for predicting the survival of patients with ovarian cancer (OvCa), and many genes have been found to be associated with OvCa prognosis. The objective of this study was to develop a model that integrates clinical information and a gene signature to predict the survival durations of patients diagnosed with OvCa. We constructed mRNA and microRNA expression profiles and gathered the corresponding clinical data of 552 OvCa patients and 8 normal controls from The Cancer Genome Atlas. Using univariate Cox regression followed by a permutation test, elastic net-regulated Cox regression, and ridge regression, we generated a prognosis index consisting of 2 clinical variables, 7 protective mRNAs, 12 risky mRNAs, and 1 protective microRNA. The area under the curve of the receiver operating characteristic of the integrated clinical-and-gene model was 0.756, larger than that of the clinical-alone model (0.686) or the gene-alone model (0.703). OvCa patients in the high-risk group had a significantly shorter overall survival time compared with patients in the low-risk group (hazard ratio = 8.374, 95% confidence interval = 4.444–15.780, P = 4.90 × 10⁻¹¹, by the Wald test). The reliability of the gene signature was confirmed by a public external data set from the Gene Expression Omnibus. Our conclusions that we have identified an integrated clinical-and-gene model superior to the traditional clinical-alone model in ascertaining the survival prognosis of patients with OvCa. Our findings may prove valuable for improving the clinical management of OvCa.

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Patient-Reported Outcomes Labeling for Products Approved by the Office of Hematology and Oncology Products of the US Food and Drug Administration (2010-2014)

open access:
JCO April 11, 2016 JCO636480
Patient-Reported Outcomes Labeling for Products Approved by the Office of Hematology and Oncology Products of the US Food and Drug Administration (2010-2014)

Table 3 Oncology Products With Potential for PRO Labeling (FDA OHOP, 2010-2014) (Olaparib/Ovarian)

Although all 13 registration trials included established PROMs (Patient Reported Outcome Measures), only 5 (38.4%) were RCTs. Significant deficiencies noted by the FDA reviewers within the DAP included unacceptable levels of missing values, use of inappropriate PROMs, and a lack of clinical significance.

Two major factors may contribute to the smaller number of PRO labeling instances in oncology drug development. First, oncology studies are significantly more likely to be small, single arm, and open label. Thus, these studies may not be perceived to be candidates for inclusion of PROs because of potential bias introduced by the open-label design.¹ Second, given that most oncology drugs are marketed first in the United States, oncology trials are likely to go through various regulatory pathways designed to speed up the development and regulatory process in the United States.²² Pressed for time and given the challenges involved in integrating PROs in clinical trials, sponsors may be unlikely to prioritize PRO end points.23,2

Conclusion Although symptoms and functional decrements are common among patients with cancer, PRO (Patient Reported Outcomes) labeling is rare in the United States, likely because of logistical hurdles and oncology study design. Recent developments within the FDA OHOP to capture PROs in oncology studies for the purpose of product labeling are encouraging.

In conclusion, the small number of PRO labeling instances granted by the FDA OHOP is a reflection of the difficulties faced by regulators and the industry to capture the patient’s voice in oncology drug development. However, recent developments within the FDA, and particularly within OHOP, to better capture PROs in oncology studies for the purpose of product labeling is encouraging. Sponsors should also make every effort to capture PROs in cancer drug development, and product labeling should not be the only goal for including PROs in drug development. PROs should be included in development programs to capture a comprehensive evaluation of the study participants’ experience, which can provide useful information on the impact of the new therapy for patients, regulators, health care providers, caregivers, and payers who need to choose between competing therapies.

Ovarian cancer in "Lynch syndrome" - Google Scholar ( search 2016)

Google Scholar

Rare ATAD5 missense variants in breast and ovarian cancer patients

Abstract
Highlights

•: ATAD5 coding region was fully sequenced in 273 patients with either triple-negative breast cancer or serous ovarian cancer as well as in 276 healthy controls.
•: Four novel mutations were found, with three of them predicted to be pathogenic.
•: Pathogenic mutations were enriched in serous ovarian cancer patients.
•: None of the mutations could explain the genome-wide association results for this locus, indicating further regulatory mechanisms to be identified.

ATAD5/ELG1 is a protein crucially involved in replication and maintenance of genome stability. ATAD5 has recently been identified as a genomic risk locus for both breast and ovarian cancer through genome-wide association studies. We aimed to investigate the spectrum of coding ATAD5 germ-line mutations in hospital-based series of patients with triple-negative breast cancer or serous ovarian cancer compared with healthy controls. The ATAD5 coding and adjacent splice site regions were analyzed by targeted next-generation sequencing of DNA samples from 273 cancer patients, including 114 patients with triple-negative breast cancer and 159 patients with serous epithelial ovarian cancer, and from 276 healthy females. Among 42 different variants identified, twenty-two were rare missense substitutions, of which 14 were classified as pathogenic by at least one in silico prediction tool. Three of four novel missense substitutions (p.S354I, p.H974R and p.K1466N) were predicted to be pathogenic and were all identified in ovarian cancer patients. Overall, rare missense variants with predicted pathogenicity tended to be enriched in ovarian cancer patients (14/159) versus controls (11/276) (p = 0.05, 2df). While truncating germ-line variants in ATAD5 were not detected, it remains possible that several rare missense variants contribute to genetic susceptibility toward epithelial ovarian carcinomas.

Apr 11, 2006: sundry articles re: aspirin (American College of Physicians journal

http://annals.org/Images/buttons/logo_ACP.png

April 11, 2016

Original Research

Aspirin for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: A Decision Analysis for the U.S. Preventive Services Task Force

Reviews

Bleeding Risks With Aspirin Use for Primary Prevention in Adults: A Systematic Review for the U.S. Preventive Services Task Force

Aspirin for the Primary Prevention of Cardiovascular Events: A Systematic Evidence Review for the U.S. Preventive Services Task Force

Aspirin for the Prevention of Cancer Incidence and Mortality: Systematic Evidence Reviews for the U.S. Preventive Services Task Force

Clinical Guidelines

Aspirin Use for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: U.S. Preventive Services Task Force Recommendation Statement
FREE

Summaries for Patients

Aspirin Use for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: Recommendations From the U.S. Preventive Services Task Force
FREE

Editorials

Aspirin for Disease Prevention: Public Policy or Personal Choice?
FREE

Bleeding Risks With Aspirin Use for Primary Prevention in Adults: A Systematic Review for the U.S. Preventive Services Task ForceBleeding Risks With Aspirin Use | Annals of Internal Medicine

abstract:
Bleeding Risks With Aspirin Use for Primary Prevention in Adults: A Systematic Review for the U.S. Preventive Services Task Force
Reviews | 12 April 2016
Background: The balance between potential aspirin-related risks and benefits is critical in primary prevention.
Purpose: To evaluate the risk for serious bleeding with regular aspirin use in cardiovascular disease (CVD) primary prevention.
Data Sources: PubMed, MEDLINE, Cochrane Central Register of Controlled Trials (2010 through 6 January 2015), and relevant references from other reviews.
Study Selection: Randomized, controlled trials; cohort studies; and meta-analyses comparing aspirin with placebo or no treatment to prevent CVD or cancer in adults.

Limitations: Power to detect effects on hemorrhagic stroke was limited. Harms other than serious bleeding were not examined.
Conclusion: Consideration of the safety of primary prevention with aspirin requires an individualized assessment of aspirin's effects on bleeding risks and expected benefits because absolute bleeding risk may vary considerably by patient.

Viewpoint: (U.S.) Medicare’s Vision for Advanced Primary Care: New Directions for Care Delivery/Payment

JAMA Network

The Other Side of Bad News - the Oncologist

Blogger's Note: not specific to ovarian cancer but many 'aha moments'

The Other Side of Bad News (open access)

Looking back, I realize that waiting for bad news is actually worse than receiving bad news.

Over the next several hours, a parade of medical professionals entered the room, each starting the conversation with “I’m sorry.” It seemed everyone was sorry, including the emergency department attending physician, the overnight admitting team, the medical intensive care team....

OCNA/OCRFA Survivors Teaching Students - needs help in Chicago area

We continue to try to bring Ovarian Cancer National Alliance/OCRFA Survivors Teaching Students(R) program to Chicago. Looking for one or more volunteers who would be willing to act as the area facilitator. This involves coordinating presentations with schools, training and scheduling presenters, and entering information in the database. If you live in Chicago area and would be interested in helping get things started there, please email me at sleighton@ocrfa.org

The Methods Man: Accuracy of Test 'Accuracy'

Medpage Today

(Opinion) Slow Medicine: ELITE Doesn't Change Our Minds on HRT (including comments)

Blogger's Note: not everyone agrees with this opinion per comments

Medpage Today

Causes of Cancer Death Among First-Degree Relatives in Japanese Families with Lynch Syndrome

abstract
Causes of Cancer Death Among First-Degree Relatives in Japanese Families with Lynch Syndrome

Aim: To elucidate the causes of cancer death in Japanese families with Lynch syndrome (LS).

Methods: The distributions of cancer deaths in 485 individuals from 67 families with LS (35, 30, and two families with MutL homologue 1 (MLH1), MSH2, and MSH6 gene mutations, respectively), obtained from the Registry of the Japanese Society for Cancer of the Colon and Rectum were analyzed.

Results: Among 98 cancer deaths of first-degree relatives of unknown mutation status, 53%, 19%, 13% (among females), 7% (among females) and 5% were due to colorectal, gastric, uterine, ovarian, and hepatobiliary cancer, respectively. The proportion of deaths from extra-colonic cancer was significantly higher in families with MSH2 mutation than in those with MLH1 mutation (p=0.003).

Conclusion: In addition to colonic and uterine cancer, management and surveillance targeting gastric, ovarian and hepatobiliary cancer are considered important for Japanese families with LS. Extra-colonic cancer in families with MSH2 mutation might require for more intensive surveillance.

Hydration with 15 mEq Magnesium Is Effective at Reducing Risk for Cisplatin-induced Nephrotoxicity in (Gyn) Pts Receiving Cisplatin...

abstract
Hydration with 15 mEq Magnesium Is Effective at Reducingthe Risk for Cisplatin-induced Nephrotoxicity in Patients Receiving Cisplatin (≥50 mg/m2) Combination Chemotherapy

Aim: We aimed to assess whether the efficacy of pre-hydration with 15 mEq magnesium prevents cisplatin-induced nephrotoxicity in cisplatin regimens (dosage: 50 mg/m² or more) for gynecological cancer.
Patients and Methods: This historical, prospective cohort study compared nephrotoxicity in patients who received pre-hydration with or without magnesium sulfate (Mg-hydration group, n=37; non-Mg-hydration group, n=37). We used serum creatinine (Scr), creatinine clearance (Ccr) and Risk, Injury, Failure, Loss of kidney function and End-stage kidney disease (RIFLE) criteria.
Results: A change of Scr and Ccr in the Mg-hydration group was higher than in the non-Mg-hydration group. Based on the RIFLE criteria, the number of moderate renal dysfunction patients classified as “Risk” in the Mg-hydration group was significantly lower than in the non-Mg-hydration group (Mg-hydration group=21.6%; non-Mg-hydration group=51.4%; p<0.01). Serum magnesium levels in the Mg-hydration group significantly declined during chemotherapy (p<0.01). Conclusion: We found that a 15 mEq magnesium as pre-hydration provided nephroprotective effects in patients receiving this cisplatin regimen. Future research should involve finding appropriate magnesium doses.

Dynamic Analysis of CA125 Decline During Neoadjuvant Chemotherapy in Patients with Epithelial Ovarian Cancer as a Predictor for Platinum Sensitivity

abstract:
Dynamic Analysis of CA125 Decline During Neoadjuvant Chemotherapy in Patients with Epithelial Ovarian Cancer as a Predictor for Platinum Sensitivity

Aim: Our objective was to evaluate the kinetic parameters of serum CA125 during neoadjuvant platinum-based chemotherapy (NAC), in patients with epithelial ovarian cancer, in order to identify a surrogate marker of sensitivity to platinum. Materials and Methods: Patients diagnosed between 2002 and 2009, and treated with NAC and interval debulking surgery, were included in the study.
Results: One hundred and forty-two patients met the study inclusion criteria. Fifty-four patients (38%) were platinum-sensitive (PFI >12 months). A CA125 level after the 3rd NAC cycle <35 UI/ml was significantly associated with improved overall survival (OS) and relapse-free survival (RFS). In the multivariate model, patients with a CA125 level after the 3rd NAC cycle >35 UI/ml were 3.8-times more at risk for PFI <12 months (95% CI=1.7-8.5, p<0.001).
Conclusion: A CA125 level after the 3rd NAC <35 UI/ml is an independent predictor for tumor platinum-sensitivity.

Atypical Right Hepatectomy for Liver Metastasis from Ovarian Leiomyosarcoma – A Case Report and Literature Review

open access:
Atypical Right Hepatectomy for Liver Metastasis from Ovarian Leiomyosarcoma – A Case Report and Literature Review

Data regarding ovarian leiomyosarcomas are scarce, only few cases have been reported so far in the literature (1, 2, 5).

Impact of Chemotherapy on Retroperitoneal Lymph Nodes in Ovarian Cancer

abstract

Background: Complete cytoreduction is the most important prognostic factor in ovarian cancer. However, there exist conflicting data on whether the removal of microscopic tumor metastasis in macroscopically unsuspicious retroperitoneal lymph nodes is beneficial.

Patients and Methods: Ovarian cancer tissues and tissues from lymph node metastasis of 30 patients with FIGO IIIC or IV disease undergoing neoadjuvant chemotherapy (NACT) were obtained and assessed using a validated regression score. Histopathological markers, size of largest tumor focus, and overall score were evaluated in lymph node and ovarian tissue. Regression and known prognostic factors were analyzed for influence on survival.

Results: No difference in the overall score between lymph nodes and ovarian tissue was shown, however, single parameters such as fibrosis and pattern of tumor infiltration, were significantly different.

Conclusion: The pattern of tumor regression in lymph nodes and ovarian tissue are of prognostic value. Lymph node dissection even of unsuspicious nodes should, therefore, be performed.

Risk of Metabolic Complications in Patients with Solid Tumors Treated with mTOR inhibitors: Meta-analysis

open access:
Risk of Metabolic Complications in Patients with Solid Tumors Treated with mTOR inhibitors: Meta-analysis

Despite its limitations, this study demonstrates that the use of mTORi is associated with a significant risk of developing all- and high-grade metabolic complications. The risk of adverse metabolic events does not differ by type of Rapamycin analog, type of malignancy treated, or when monotherapy or concomitant therapy is utilized. Early detection and effective management of HGL, HTG, and HCE may allow for more extensive use of mTORi therapy, especially in cancer patients with pre-existing metabolic comorbidities, and should limit treatment related toxicity.

(Lynparza) Olaparib maintenance therapy in patients with platinum-sensitive, relapsed serous ovarian cancer....

Blogger's note: search this blog using term: olaparib (numerous postings)

Abstract:
Olaparib maintenance therapy in patients with platinum-sensitive, relapsed serous ovarian cancer and a BRCA mutation: Overall survival adjusted for postprogression poly(adenosine diphosphate ribose) polymerase inhibitor therapy

BACKGROUND

Maintenance treatment with the oral poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor olaparib (Lynparza) in Study 19 (study number, D0810C00019; ClinicalTrials.gov identifier, NCT00753545) significantly improved progression-free survival in comparison with a placebo for patients with platinum-sensitive, relapsed serous ovarian cancer with a BRCA1/2 mutation (BRCAm), but an interim analysis revealed no statistically significant overall survival (OS) benefit. However, 23% of the patients receiving the placebo switched to a PARP inhibitor after progression. To investigate whether this had a confounding effect on OS, this article reports an exploratory post hoc analysis that excluded all patients from sites where 1 or more placebo patients received postprogression PARP inhibitor treatment.

METHODS

In Study 19, 136 of the 265 patients receiving olaparib or a placebo had a BRCAm. Sixteen patients treated at 11 of the 82 investigational sites received a PARP inhibitor after progression; these sites were excluded from this analysis, and 97 BRCAm patients at 50 sites were included. OS was assessed with a Cox proportional hazards model analogous to the primary study analysis. A supporting rank-preserving structural failure time (RPSFT) model analysis was undertaken for all 136 BRCAm patients.

RESULTS

The OS hazard ratio (HR) was 0.52 (95% confidence interval [CI], 0.28-0.97) for the 97 BRCAm patients, whereas for the interim OS analysis with all 136 BRCAm patients, it was 0.73 (95% CI, 0.45-1.17). The supportive RPSFT analysis HR was approximately 0.66.

CONCLUSIONS

The numerical improvement in the OS HR suggests that in Study 19, postprogression PARP inhibitor treatment had a confounding influence on the interim OS analysis for BRCAm patients. There is a degree of uncertainty due to the small sample size and the lack of data maturity.

Nonbleeding adenomas: Evidence of systematic false-negative FIT results and their implications for screening effectiveness

abstract
Nonbleeding adenomas: Evidence of systematic false-negative fecal immunochemical test results and their implications for screening effectiveness–A modeling study

BACKGROUND

If some adenomas do not bleed over several years, they will cause systematic false-negative fecal immunochemical test (FIT) results. The long-term effectiveness of FIT screening has been estimated without accounting for such systematic false-negativity. There are now data with which to evaluate this issue.

CONCLUSIONS

The results of the current study provide convincing evidence based on the combination of real-life and modeling data that a percentage of adenomas are systematically missed by repeat FIT screening. This impairs the efficacy of FIT screening.

Perceptions of cancer in society must change - The Lancet Oncology

The Lancet Oncology

Cancer is becoming an ever-expanding presence in our society, and we would benefit from reconciling its ability to scare and isolate with its ubiquity and survivability. No longer the big ‘C’, cancer must be appraised realistically. An increasing focus and reflection on cancer in the mainstream media is a good way of destigmatising and desensitising issues among the general public, while also bringing comfort, hope, and perhaps, some useful advice to patients and survivors alike.

Cochrane GRADE working group (re: FB post Q & A - evidence grading systems)

GRADE working group

Are grading evidence and recommendations something new?

Not really. Grading schemes have been used for over 30 years.

There are so many systems for grading evidence and recommendations out there. Why do we need another one?

Because there is a need for one single system to avoid confusion. The single system should avoid shortcomings of other systems and include their strengths. Some grading systems are based on study design alone without explicit consideration of other important factors in determining quality of evidence. Some systems are excessively complex. An analysis of current grading systems has shown that these and other shortcomings have not been adequately addressed by any one system to date. See: How GRADE compares to other systems

(U.S.) FDA Alert: Metformin-containing Drugs: Drug Safety Communication - Revised Warnings for Certain Patients With Reduced Kidney Function

Revised Warnings

See the FDA Drug Safety Communication for additional information, including a data summary and a list of metformin-containing drugs.

The labeling recommendations on how and when kidney function is measured in patients receiving metformin will include the following information:

Before starting metformin, obtain the patient’s eGFR.
Metformin is contraindicated in patients with an eGFR below 30 mL/minute/1.73 m².
Starting metformin in patients with an eGFR between 30-45 mL/minute/1.73 m² is not recommended.
Obtain an eGFR at least annually in all patients taking metformin. In patients at increased risk for the development of renal impairment such as the elderly, renal function should be assessed more frequently.
In patients taking metformin whose eGFR later falls below 45 mL/minute/1.73 m², assess the benefits and risks of continuing treatment. Discontinue metformin if the patient’s eGFR later falls below 30 mL/minute/1.73 m².
Discontinue metformin at the time of or before an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/minute/1.73 m²; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure; restart metformin if renal function is stable.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

Complete and submit the report Online: www.fda.gov/MedWatch/report

Saturday, April 09, 2016

On Carbs and Cancer: The “sugar is poison” ideology is wrong

Cure Today
article author: Amanda Bontempo

Amanda is a nutritionist and registered dietitian having received a bachelor's of science degree and master's of science degree from New York University. She has worked in oncology for over five years and consults with progressive health and technology companies in New York City. She's passionate about food and an equal lover of kale and chocolate.

Post-menopausal women taking metformin for diabetes may be at lower risk of cancer

science news

Date: April 7, 2016

Compared to women without diabetes, women with diabetes had a 13% higher risk of developing invasive cancer. These women also face increased risk that ranges from 20% to nearly double the chances of being diagnosed with the following cancers: colon, liver, pancreas, endometrial and non-Hodgkin lymphoma. Results also show that metformin use was associated with better survival in diabetes patients diagnosed with ovarian, colorectal and breast cancer.

The researchers say future studies are needed to further clarify the long-term impact of metformin on cancer risk and survival.

Journal Reference:

Zhihong Gong, Aaron K. Aragaki, Rowan T. Chlebowski, JoAnn E. Manson, Thomas E. Rohan, Chu Chen, Mara Z. Vitolins, Lesley F. Tinker, Erin S. LeBlanc, Lewis H. Kuller, Lifang Hou, Michael J. LaMonte, Juhua Luo, Jean Wactawski-Wende. Diabetes, metformin and incidence of and death from invasive cancer in postmenopausal women: Results from the women's health initiative. International Journal of Cancer, 2016; 138 (8): 1915 DOI: 10.1002/ijc.29944

Is a popular painkiller (acetaminophen) hampering our ability to notice errors?

science news
Date: April 8, 2016

It's been known for more than a century that acetaminophen is an effective painkiller, but according to a new U of T study it could also be impeding error-detection in the brain.

The research, authored by a team including postdoctoral fellow Dan Randles and researchers from the University of British Columbia, is the first neurological study to look at how acetaminophen could be inhibiting the brain response associated with making errors.
"Past research tells us physical pain and social rejection share a neural process that we experience as distress, and both have been traced to same part of the brain," says Randles.
Recent research has begun to show how exactly acetaminophen inhibits pain, while behavioural studies suggest it may also inhibit evaluative responses more generally. Randles own past research has found that people are less reactive to uncertain situations when under the effect of acetaminophen.
"The core idea of our study is that we don't fully understand how acetaminophen affects the brain," says Randles. "While there's been recent behavioural research on the effects of acetaminophen, we wanted to have a sense of what's happening neurologically."....

Journal Reference:

Daniel Randles, Julia W.Y. Kam, Steven J. Heine, Michael Inzlicht, Todd C. Handy. Acetaminophen attenuates error evaluation in cortex. Social Cognitive and Affective Neuroscience, 2016; nsw023 DOI: 10.1093/scan/nsw023

Review: Management of patients at high risk for breast and ovarian cancer

open access

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Mar 2016. | This topic last updated: Mar 21, 2016.

INTRODUCTION — The majority of patients with hereditary breast and ovarian cancers have mutations in either the breast cancer type 1 or 2 susceptibility genes (BRCA1 and BRCA2; referred in this topic as BRCA). Mutations in these genes are implicated in about 15 percent of women with familial breast cancer and a similar proportion of all women with incident ovarian cancers [1,2].....

Role of CT urography in the clinical evaluation of upper tract urothelial carcinoma (of interest to Lynch Syndrome patients)

Blogger's note: this paper does not deal with genetics, note also that MRI is useful in UTUC

open access

Abstract

Intravenous urography has been widely used for the evaluation of upper tract urothelial carcinoma. However, computed tomography urography presently has a higher diagnostic accuracy for upper tract urothelial carcinoma (94.2–99.6%) than intravenous urography (80.8–84.9%), and has replaced intravenous urography as the first-line imaging test for investigating patients with a high risk of upper tract urothelial carcinoma. Although the detection rate for bladder tumors using standard computed tomography urography is not yet high enough to replace cystoscopy, the addition of a 60- to 80-s delayed scan after the administration of contrast material for the whole pelvis improves the detection rate. A drawback to computed tomography urography is the higher radiation dose of 15–35 mSv, compared with a mean effective dose of 5–10 mSv for intravenous urography. Among several approaches to reducing the radiation dose, the use of an iterative reconstruction algorithm is most likely to become an effective solution because of its simplicity. One advantage of computed tomography urography over intravenous urography is its ability to reliably differentiate between upper tract urothelial carcinoma and calculi or blood clots. Computed tomography urography also shows characteristic findings of other benign conditions. These findings, in combination with negative cytology, are very important diagnostic clues for avoiding an unnecessary nephroureterectomy. For the clinical staging, a recent study has reported the high diagnostic accuracy of computed tomography urography with respect to ≥pT3 tumors. The present review shows the current status of computed tomography urography for the evaluation of upper tract urothelial carcinoma.

Introduction

Tumors of the renal pelvis and ureter are rare, and account for just 8% of all urinary tract neoplasms; of these, more than 90% are urothelial carcinomas.[1] The incidence of these tumors is 0.7–1.1 per 100 000, and has increased slightly.[1] Recently, several advances have been made in the treatment of UTUC. Developments in endoscopic management have enabled less invasive therapy for small, low-grade, Ta or T1 UTUC,[2, 3] whereas neoadjuvant chemotherapy and lymph node dissection have improved the prognostic outcomes for muscle-invasive or locally advanced UTUC.[4-8] These developments have, more than ever, emphasized the importance of earlier detection and accurate UTUC staging using imaging modalities. Furthermore, considering that 8.5–13% of patients with UTUC have synchronous bladder cancer and 15–50% of patients with UTUC will develop bladder cancer, the need for non-invasive bladder surveillance at the initial examination or at follow-up examinations of these patients should be underscored.[9].....

Prediction of taxane and platinum sensitivity in ovarian cancer based on gene expression profiles

abstract (technical)

Highlights

•: Gene expression-driven scores predict platinum/taxane response
•: Association of proposed scores with HGSOC gene expression subtypes
•: Complimentary roles of platinum and taxane for personalized therapy

Objective

Prognoses of ovarian cancer (OC) have improved with the paclitaxel-carboplatin regimen. However, it remains unclear which cases exhibit a genuine benefit from taxane or from platinum. We aimed to predict taxane and platinum sensitivity in OC via gene expression.

Conclusions

Our proposal and finding of a scoring system that could predict platinum or taxane response could be useful to develop individualized treatments to ovarian cancer.

A new clinically applicable age-specific comorbidity index for preoperative risk assessment of ovarian cancer patients

Abstract

Highlights

•: Self-reported comorbidity is useful for risk-assessment in ovarian cancer.
•: This new comorbidity index risk-scores patients according to overall survival.
•: The index may help to ensure individualized treatment of ovarian cancer patients.

Objective

To develop and validate a new feasible comorbidity index based on self-reported information suited for preoperative risk assessment of ovarian cancer patients.

Moving beyond the platinum sensitive/resistant paradigm for patients with recurrent ovarian cancer

highlights only - commentary (full acess requires $$)

Highlights

•: It is timely to reconsider how patients with recurrent ovarian cancer are classified.
•: Categorizing recurrent ovarian cancer patients only on basis of a timeline is limited.
•: A multiplex system of categorizing patients with recurrent ovarian cancer is needed.

Targeting the hallmarks of ovarian cancer: The big picture

abstract

Highlights

•: Genomic instability and angiogenesis appear as the cornerstone in molecularly-driven therapy in high-grade serous OC.
•: Targeting sustained proliferative signaling seems the most promising approach for low-grade and clear cell OC.
•: Evasion of immune destruction is the emerging target in high-grade serous OC.

Objective

As a result of relevant achievements in the field of translational research, several active drugs and multiple biological targets are available in ovarian cancer (OC). In this complex scenario, there is an urgent need to effectively summarize the available data in order to update conclusions, and outline perspectives.