Role of Immunosuppressive Molecules in Ovarian Cancer - Ovarian Cancer Research Fund

Jessica Chacon, Ph.D.

 The University of Pennsylvania
Investigating the Role of Immunosuppressive Molecules in Ovarian Cancer

Pioneering Oncologist Discusses "The Death of Cancer" (short videos - 4)

CURETODAY - Markman interviews Dr DeVita

Dr. Maurie Markman sits down with Dr. Vincent T. DeVita, one of the most influential researchers and physicians in the cancer care arena.

This is part I of a four-part interview.

View part II of the interview here
Part III here
Part IV here

Measurement of the (U.S.) Patient Experience: Clarifying Facts, Myths, and Approaches

JAMA Viewpoint (open access)

 The Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey is a 32-item tool administered after discharge to a random sample of adult inpatients, creating standardized, publicly reported metrics that allow fair comparisons of patient experience in hospitals across the nation. The 11 HCAHPS measures derived from the survey reported on the Hospital Compare website assess how well nurses and physicians communicate with patients, how responsive hospital staff are to patients’ needs, how well hospital staff help patients manage pain, how well the staff communicates with patients about new medicines, whether key information is provided at discharge, how smoothly the transition to the posthospital setting is made, how clean and quiet are the patients’ rooms, what is the hospital’s overall rating, and whether the patient would recommend the hospital.^1....

References

1

Centers for Medicare & Medicaid. Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS): Centers for Medicare & Medicaid Services. http://www.hcahpsonline.org/HospitalVBP.aspx. Published 2015. Accessed October 30, 2015.

2

Halbesleben  JR, Whitman  MV.  Evaluating survey quality in health services research: a decision framework for assessing nonresponse bias. Health Serv Res. 2013;48(3):913-930.
PubMed   |  Link to Article

3

Elliott  MN, Zaslavsky  AM, Goldstein  E,  et al.  Effects of survey mode, patient mix, and nonresponse on CAHPS hospital survey scores. Health Serv Res. 2009;44(2 pt 1):501-518.
PubMed   |  Link to Article

4

Johnson  TP, Wislar  JS.  Response rates and nonresponse errors in surveys. JAMA. 2012;307(17):1805-1806.
PubMed   |  Link to Article

5

Chatterjee  P, Tsai  TC, Jha  AK.  Delivering value by focusing on patient experience. Am J Manag Care. 2015;21(10):735-737.
PubMed

6

Gunderman  R. When physicians’ careers suffer because they refuse to prescribe narcotics. The Atlantic. http://www.theatlantic.com/health/archive/2013/10/when-physicians-careers-suffer-because-they-refuse-to-prescribe-narcotics/280995/. Published October 30, 2013. Accessed February 29, 2016.

7

Zgierska  A, Rabago  D, Miller  MM.  Impact of patient satisfaction ratings on physicians and clinical care. Patient Prefer Adherence. 2014;8:437-446.
PubMed   |  Link to Article

8

Carrus  B, Cordina  J. Measuring the patient experience: lessons from other industries. http://healthcare.mckinsey.com/measuring-patient-experience-lessons-other-industries. Published August 2015. Accessed January 12, 2016.

9

Elliott  MN, Kanouse  DE, Edwards  CA, Hilborne  LH.  Components of care vary in importance for overall patient-reported experience by type of hospitalization. Med Care. 2009;47(8):842-849.
PubMed   |  Link to Article

Psychological difficulties of ovarian cancer: an interview (UK)

Psychological difficulties
 Psychological difficulties of ovarian cancer: an interview with Katherine Taylor

  There’s really no part of a women’s life that would remain untouched by a diagnosis of ovarian cancer.

Rich Hospital Donors Not Protected by HIPAA

medpage blog

How Should Research Be Funded? Difficulties With the Argument for Proportionality to Causes of Death or Years of Life Lost

open access:
How Should Research Be Funded? Difficulties With the Argument for Proportionality to Causes of Death or Years of Life Lost

Conclusions

It is highly likely that the current funding system is suboptimal. It may also be likely that cancer groups that are the most vocal and well organized, and lack societal stigma (eg, non–smoking-related cancers), may generate disproportionate and perhaps unjustified funding. However, the common argument that research funding should be proportionate to causes of death or years of life lost is incorrect. What kills us and what robs of us of life simply approximate where progress is most likely to be achieved. They remain surrogates or stand-ins of where we may derive the most benefit. Appreciation of this fact may lead to more constructive debates about equitable cancer research funding and donation by tumor type.

Are strong opioids equally effective and safe in the treatment of chronic cancer pain?....

abstract:
Are strong opioids equally effective and safe in the treatment of chronic cancer pain? A multicenter randomized phase 4 ‘real life’ trial on the variability of response to opioids
 

Background Guidelines tend to consider morphine and morphine-like opioids comparable and interchangeable in the treatment of chronic cancer pain but individual responses can vary. This study compared the analgesic efficacy, changes of therapy and safety profile over time of four strong opioids given for cancer pain. 

Patient and methods In this four-arm multicenter, randomized, comparative, of superiority, phase IV trial, oncological patients with moderate to severe pain requiring WHO step III opioids were randomly assigned to receive oral morphine or oxycodone or transdermal fentanyl or buprenorphine for 28 days. At each visit, pain intensity, modifications of therapy and adverse drug reactions were recorded. The primary efficacy endpoint was the proportion of non-responders, meaning patients with worse or unchanged average pain intensity between the first and last visit, measured on a 0 to 10 numerical rating scale. (NCT01809106) 

Results Forty-four centers participated in the trial and recruited 520 patients. Worst and average pain intensity decreased over four weeks with no significant differences between drugs. Non-responders ranged from 11.5% for morphine to 14.4% for buprenorphine. Appreciable changes were made in the treatment schedules over time. Each group required increases in the daily dose, from 32.7% with morphine to 121.2% with transdermal fentanyl. Patients requiring adjuvant analgesics ranged from 68.9% (morphine) to 81.6% (oxycodone), switches varied from 22.1% with morphine to 12% with oxycodone, discontinuation of treatment from 27% with morphine to 14.5% with fentanyl. Adverse drug reactions were similar except for effects on the nervous system, which significantly prevailed with morphine. 

Conclusion The main findings were the similarity in pain control, response rates and main adverse reactions among opioids. Changes in therapy schedules were notable over time. A considerable proportion of patients were non or poor responders.

Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation...

abstract:
Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multi-study analysis of response rates and safety
 

Background The PARP inhibitor olaparib (Lynparza™) demonstrates antitumor activity in women with relapsed ovarian cancer and a germline BRCA1/2 mutation (gBRCAm). Data from olaparib monotherapy trials were used to explore the treatment effect of olaparib in patients with gBRCAm ovarian cancer who had received multiple lines of prior chemotherapy. 

Patients and methods This analysis evaluated pooled data from two Phase I trials (NCT00516373 [Study 2]; NCT00777582 [Study 24]) and four Phase II trials (NCT00494442 [Study 9]; NCT00628251 [Study 12]; NCT00679783 [Study 20]; NCT01078662 [Study 42]) that recruited women with relapsed ovarian, fallopian tube or peritoneal cancer. All patients had a documented gBRCAm and were receiving olaparib 400 mg monotherapy twice daily (capsule formulation) at the time of relapse. Objective response rate (ORR) and duration of response (DoR) were evaluated using original patient outcomes data for patients with measurable disease at baseline. 

Results Of the 300 patients in the pooled population, 273 had measurable disease at baseline, of whom 205 (75%) had received ≥3 lines of prior chemotherapy. In the pooled population, the ORR was 36% (95% CI: 30, 42) and the median DoR was 7.4 months (95% CI: 5.7, 9.1). The ORR among patients who had received ≥3 lines of prior chemotherapy was 31% (95% CI: 25, 38), with a DoR of 7.8 months (95% CI: 5.6, 9.5). The safety profile of olaparib was similar in patients who had received ≥3 lines of prior chemotherapy compared with the pooled population; grade ≥3 adverse events were reported in 54% and 50% of patients, respectively. 

Conclusion Durable responses to olaparib were observed in patients with relapsed gBRCAm ovarian cancer who had received ≥3 lines of prior chemotherapy. 

Clinical trial numbers ClinicalTrials.gov, NCT00516373; NCT00494442; NCT00628251; NCT00679783; NCT00777582; NCT01078662

Assessing the readability of ClinicalTrials.gov

Abstract

Objective ClinicalTrials.gov serves critical functions of disseminating trial information to the public and helping the trials recruit participants. This study assessed the readability of trial descriptions at ClinicalTrials.gov using multiple quantitative measures.
 Discussion and Conclusion Trial descriptions at CliniclTrials.gov are extremely difficult to read. Significant work is warranted to improve their readability in order to achieve CliniclTrials.gov’s goal of facilitating information dissemination and subject recruitment.

Amino acids: Medical Encyclopedia

MedlinePlus Medical Encyclopedia

 Amino acids

Amino acids are organic compounds that combine to form proteins. Amino acids and proteins are the building blocks of life.
When proteins are digested or broken down, amino acids are left. The human body uses amino acids to make proteins to help the body:

• Break down food
• Grow
• Repair body tissue
• Perform many other body functions

Amino acids can also be used as a source of energy by the body.
Amino acids are classified into three groups:

• Essential amino acids
• Nonessential amino acids
• Conditional amino acids

Essential amino acids

• Essential amino acids cannot be made by the body. As a result, they must come from food.
• The 9 essential amino acids are: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine.

Nonessential amino acids

• "Nonessential" means that our bodies produce an amino acid, even if we do not get it from the food we eat.
• Nonessential amino acids include: alanine, asparagine, aspartic acid, and glutamic acid.

Conditional amino acids

• Conditional amino acids are usually not essential, except in times of illness and stress.
• Conditional amino acids include: arginine, cysteine, glutamine, tyrosine, glycine, ornithine, proline, and serine.

You do not need to eat essential and nonessential amino acids at every meal, but getting a balance of them over the whole day is important. A diet based on a single plant item will not be adequate but we no longer worry about pairing proteins (such as beans with rice) at a single meal. Instead we look at the adequacy of the diet overall throughout the day.

Scientists surprised to find that amino acids, not sugar, supply most building blocks for tumor cells

medical news

National Nutrition Research Roadmap 2016 ‒ 2021 : Advancing Nutrition Research to Improve and Sustain Health

 ICHNR NNRR (2)_0.pdf (176 pages)

 The NIH also supports research that informs best practices for medical nutrition therapy of an array of acute and chronic diseases and conditions, to mitigate symptoms, delay progression, and prevent complications. These include studies of the biological mechanisms and effectiveness of dietary approaches for management of conditions such as cardiovascular disease, type 1 and type 2 diabetes mellitus, obesity, chronic kidney disease, inborn errors of metabolism, inflammatory bowel disease, food allergy, and consequences of cancer treatment modalities (e.g., surgery, radiation, chemotherapy).

JAMA Dermatology: Healing the Bee’s Knees—On Honey and Wound Healing

JAMA Network (full access requires $$)

 Since antiquity, honey has been revered for its natural healing properties. It has been used for treatment of gastrointestinal tract illnesses, treatment of pain, and defense from infection. However, it is its historical use in the treatment of skin wounds, burns, and ulcers that has sparked a renewed interest in recent years. Emerging scientific study of honey’s therapeutic mechanisms has provided evidence for the antimicrobial and wound healing benefits behind this enduring tradition.

AIRC: Report Finds Need to Focus on Ovarian Cancer Subtypes for Prevention, Research

CRU

 The Ovarian Cancer International Consortium is one such collaboration pooling data that is providing valuable evidence to improve our understanding of the etiology of the different ovarian cancer histologic subtypes, says Bandera, but more work needs to be done in this area.

conference notice:(AICR) 25th Research Conference Nutrition, Physical Activity, Obesity & Cancer Nov 14-16, 2016

AICR

Important Dates:

• Registration and Hotel will open in June. • Posters and Scholarship Applications will open in June

 About the Conference:
AICR's Annual Research Conference is a unique forum that brings together researchers and clinicians for a three-day program that is dedicated to increasing knowledge, stimulating research and promoting prevention and treatment of cancer through nutrition, physical activity and weight management.

The 25th AICR Research Conference will take place November 14 - 16, 2016 in North Bethesda, MD.
Stay tuned for more information and be sure to sign up to receive updates.

Who Should Attend:

Basic scientists, clinical investigators, epidemiologists, dietitians, nutritionists, policy makers and other health professionals interested in food, nutrition, physical activity and weight management in relation to cancer.

Media Reporting of Practice-Changing Clinical Trials in Oncology: A North American Perspective

abstract
 

Introduction.

Media reporting of clinical trials impacts patient-oncologist interactions. We sought to characterize the accuracy of media and Internet reporting of practice-changing clinical trials in oncology.

Materials and Methods.

The first media articles referencing 17 practice-changing clinical trials were collected from 4 media outlets: newspapers, cable news, cancer websites, and industry websites. Measured outcomes were media reporting score, social media score, and academic citation score. The media reporting score was a measure of completeness of information detailed in media articles as scored by a 15-point scoring instrument. The social media score represented the ubiquity of social media presence referencing 17 practice-changing clinical trials in cancer as determined by the American Society of Clinical Oncology in its annual report, entitled Clinical Cancer Advances 2012; social media score was calculated from Twitter, Facebook, and Google searches. The academic citation score comprised total citations from Google Scholar plus the Scopus database, which represented the academic impact per clinical cancer advance.

Results.

From 170 media articles, 107 (63%) had sufficient data for analysis. Cohen’s κ coefficient demonstrated reliability of the media reporting score instrument with a coefficient of determination of 94%. Per the media reporting score, information was most complete from industry, followed by cancer websites, newspapers, and cable news. The most commonly omitted items, in descending order, were study limitations, exclusion criteria, conflict of interest, and other. The social media score was weakly correlated with academic citation score.

Conclusion.

Media outlets appear to have set a low bar for coverage of many practice-changing advances in oncology, with reports of scientific breakthroughs often omitting basic study facts and cautions, which may mislead the public. The media should be encouraged to use a standardized reporting template and provide accessible references to original source information whenever feasible.

Implications for Practice:

North American newspapers, cable news, cancer websites, and industry websites were searched for their reporting on 17 practice-changing clinical trials in oncology as highlighted by the American Society of Clinical Oncology in its 2012 annual report, Clinical Cancer Advances. Accuracy of reporting across media platforms was evaluated, and the social media buzz and academic interest generated by each clinical trial was gauged. The findings represent, to the authors’ knowledge, the first systematic effort to appraise the reporting of practice-changing clinical trials in oncology across various media platforms. Use of a standardized reporting template by the media is proposed to reduce flaws in their reporting of clinical trials to the public.

Physician-assisted death: we want your feedback - Sunnybrook Hospital

Physician-assisted death: we want your feedback - Sunnybrook Hospital (Toronto)

2 simple questions - at home/in hospital

Consumer Perceptions of Interactions With Primary Care Providers After Direct-to-Consumer Personal Genomic Testing

abstract
Consumer Perceptions of Interactions With Primary Care Providers After Direct-to-Consumer Personal Genomic Testing


Primary Funding Source: National Institutes of Health.


Background: Direct-to-consumer (DTC) personal genomic testing (PGT) allows individuals to learn about their genetic makeup without going through a physician, but some consumers share their results with their primary care provider (PCP).
Objective: To describe the characteristics and perceptions of DTC PGT consumers who discuss their results with their PCP.
Design: Longitudinal, prospective cohort study.
Setting: Online survey before and 6 months after results.
Participants: DTC PGT consumers.
Measurements: Consumer satisfaction with the DTC PGT experience; whether and, if so, how many results could be used to improve health; how many results were not understood; and beliefs about the PCP's understanding of genetics. Participants were asked with whom they had discussed their results. Genetic reports were linked to survey responses.
Results: Among 1026 respondents, 63% planned to share their results with a PCP. At 6-month follow-up, 27% reported having done so, and 8% reported sharing with another health care provider only. Common reasons for not sharing results with a health care provider were that the results were not important enough (40%) or that the participant did not have time to do so (37%). Among participants who discussed results with their PCP, 35% were very satisfied with the encounter, and 18% were not at all satisfied. Frequently identified themes in participant descriptions of these encounters were actionability of the results or use in care (32%), PCP engagement or interest (25%), and lack of PCP engagement or interest (22%).
Limitation: Participants may not be representative of all DTC PGT consumers.
Conclusion: A comprehensive picture of DTC PGT consumers who shared their results with a health care provider is presented. The proportion that shares results is expected to increase with time after testing as consumers find opportunities for discussion at later appointments or if results become relevant as medical needs evolve.

International Women's Day Google Doodle 2016: #OneDayIWill

YouTube

International Women's Day Doodle 2016: #OneDayIWill

googledoodles

Published on Mar 7, 2016

Over the years, Doodles have marked the achievements of women in science, civil rights, journalism, sports, arts, technology and beyond. But for our 2016 International Women’s Day Doodle, we wanted to celebrate the next generation of Doodle-worthy women—the engineers, educators, leaders, movers and shakers of tomorrow.

So we visited 13 cities around the world and asked 337 girls and women to complete the sentence “One Day I Will...” Then, we made this video.

From San Francisco, Rio de Janeiro, Mexico City, Lagos, Moscow, Cairo, Berlin, London, Paris, Jakarta, Bangkok, New Delhi and Tokyo, the women we met make up a diverse mosaic of personalities, ages and backgrounds. And their aspirations are just as varied—ranging from the global to the very personal, from discovering more digits of pi to becoming a mother to giving a voice to those who can’t speak.

We also asked some more familiar figures to participate, including anthropologist Jane Goodall—who wants to discuss the environment with the Pope—and Nobel Prize Winner Malala Yousafzai and activist Muzoon Almellehan, who are working fearlessly toward a future where every girl can go to school. Despite already impressive accomplishments under their belts, these women continue to dream big.

Genetic Test Firm to Put Customers’ Data in Public Domain

The New York Times

 The 10,000 people all have or have had breast or ovarian cancer and were tested by Ambry to see if they have genetic variants that increase the risk of those diseases. Ambry returned to the samples from those customers and, at its own expense, sequenced their exomes — the roughly 1.5 percent of a person’s genome that contains the recipes for the proteins produced by the body.

AmbryShare will not contain the actual exome of each person, because that would pose a risk to patient privacy. Rather it will contain aggregated data on the genetic variants.

 

Specialists welcomed Ambry’s move, but some said it was unclear how useful the information will be. The Exome Aggregation Consortium, an academic collaboration based at the Broad Institute of M.I.T. and Harvard, already has a similar publicly available database containing information from more than 60,000 exomes.

“It is not clear to me that 10,000 exomes changes the game much,” said David B. Goldstein, professor of genetics at Columbia University.

The impact of comorbidity on cancer and its treatment

open access

Introduction

Chronic diseases are generally more common among the elderly than younger adults, and many of these are not life threatening in the short term. Consequently, many people live with, rather than die from, chronic health conditions. Cancer itself is a chronic disease with long-term consequences for health and quality of life and is more prevalent among older people. Comorbidity among cancer patients is therefore common. Data from Medicare beneficiaries in the United States (ie, for patients aged 65 years or older) indicate that four of ten patients with cancer have at least one other chronic condition recorded, and 15% have two or more, with the most common chronic conditions including cardiovascular illness, obesity and metabolic illness, mental health problems, and musculoskeletal conditions.[1] The coexistence of cancer and other chronic conditions has substantial implications for treatment decisions and treatment outcomes for both cancer and chronic disease.[2-6] Most guidelines of cancer treatment do not consider the complex interrelations between cancer and comorbidity and instead adopt a “single-disease” approach to management. With increasing subspecialization in medicine and surgery, providers are often not skilled in managing the wide spectrum of different diseases that may be present in individual patients with cancer, potentially negatively impacting patient outcomes.[6].....

Novel hereditary breast cancer gene mutations: Should there be greater concern regarding ovarian cancer risk?

Abstract

INTRODUCTION:

As the use of multi-gene breast cancer panel testing increases the phenotype of the included genes continues to evolve. PALB2 and NBN have a well characterized association with breast cancer and are included on many breast cancer gene panels. Germline PALB2 and NBN mutations have been identified in a small percentage of ovarian carcinoma cases with one study reporting a non-significant twofold increase in carriers of the PALB2 mutations amongst ovarian cancer patients (P= 0.4). Similar to BRCA1 and BRCA2 both genes are members of the Fanconi Anemia pathway therefore a potential increased risk for both breast and ovarian cancer could be anticipated. However at present overall the current literature on the association with ovarian cancer is sparse. Here we present the cases of three hereditary breast and ovarian cancer families found to carry pathogenic mutations within the PALB2 and NBN genes. In all three families the proband was diagnosed with ovarian or fallopian tube cancer and carries a pathogenic PALB2 or NBN mutation. Our PALB2 family carries the well-known French Canadian founder mutation, c.2323C>T, and includes the proband who was diagnosed with a stage II-C, grade 3, fallopian tube carcinoma at age 58, her heterozygote sister with ovary cancer at 68 and her mother with ovary cancer at 43 who was not able to be tested. This PALB2 proband has 5 sisters, 7 brothers and 41 nieces and nephews with only one sister diagnosed with breast cancer at 69 who also is PALB2 positive and a maternal grandmother with breast cancer at 48 who was unable to be tested. The NBN Slavic founder mutation, c.657_661del, was discovered in a 66 year old woman with stage IV, high-grade serous ovarian cancer having a mother with breast cancer at 91 and a maternal aunt with ovary cancer at 59 who have not yet been tested. Lastly, our patient from Laos with a diagnosis of a stage II-C endometrioid adenocarcinoma of the ovary diagnosed at 38 years old was found to carry the deleterious NBN mutation, c.1550dupA. She is not aware of any cancer family history and reports a large family including five brothers, four sisters and multiple aunts and uncles on both side of the family.

CONCLUSION:

These case studies suggest a link between PALB2 and NBN, two known breast cancer susceptibility genes, and hereditary ovarian cancer risk. These observations suggest that further data are needed to accurately evaluate ovarian cancer risk within novel hereditary breast cancer genes now commonly tested as part of multiplex panel analysis.

2016 CME: Do You Think Like the Experts? An Interactive Discussion of Clinical Scenarios in Ovarian Cancer

 

 Activity Overview

This CME-certified, interactive Webcast contains polling, video, and downloadable slides from the highly interactive symposium Do You Think Like the Experts? An Interactive Discussion of Clinical Scenarios in Ovarian Cancer, a prIME Oncology educational activity that was held on 23 January 2016 at the Progress and Controversies in Gynecologic Oncology Conference in Barcelona, Spain.

Topics

Welcome, introduction of faculty, and explanation of format
Bradley J. Monk, MD, FACS, FACOG
What’s compelling in the management of ovarian cancer in 2016?
Nicoletta Colombo, MD
Upfront therapy of advanced ovarian cancer
Antonio González Martín, MD
Platinum-sensitive relapse: Role of BRCA mutation status?
Philipp Harter, MD
Platinum-sensitive relapse: Role of antiangiogenic therapy and secondary cytoreduction?
Mansoor Mirza, MD
Platinum resistant/refractory relapse
Bradley J. Monk, MD, FACS, FACOG

On the Road (to a Cure?) — Stem-Cell Tourism and Lessons for Gene Editing

open access — NEJM (Perspective)

'I knew before I was told': Breaches, cues and clues in the diagnostic...ovarian cancer

abstract
 'I knew before I was told': Breaches, cues and clues in the diagnostic assemblage.

 Diagnosis can be both a 'diagnostic moment', but also a process over time. This paper uses secondary analysis of narrative interviews on ovarian cancer, antenatal screening and motor neurone disease to explore how people relate assembling procedural, spatial and interactional evidence before the formal diagnostic moment. We offer the idea of a diagnostic assemblage to capture the ways in which individuals connect to and re-order signs and events that come to be associated with their bodies. Building on the empirical work of Poole and Lyne (2000) in the field of breast cancer diagnosis, we identify how patients describe being alerted to their diagnosis, either through 'clues' they report picking up (often inadvertently) or through 'cues', perceived as a more intentional prompt given by a health professional, or an organisational process. For patients, these clues frequently represent a breach in the expected order of their encounter with healthcare. Even seemingly mundane episodes or behaviours take on meanings which health professionals may not themselves anticipate. Our findings speak to an emergent body of work demonstrating that experiences of formal healthcare during the lead-up to diagnosis shape patients' expectations, degree of trust in professionals, and even health outcomes.

Equivalency challenge: Evaluation of lipodox® as the generic equivalent for doxil® in a human ovarian cancer orthotropic mouse model

abstract

BACKGROUND:

The objective of this study was to evaluate the in vivo growth inhibition activity and tumor distribution of Doxil® compared to Lipodox® as its generic (GLD) in human ovarian cancer orthotopic mouse model.

CONCLUSION:

Significant differences in preclinical efficacy were observed between Doxil® and GLD. These may be due significant pharmacodynamic effects of drug distribution and decrease uptake of GLD in tumor tissue A prospective clinical comparison of these two products is warranted to determine equivalency.

Surrogate End Points and Their Validation in Oncology Clinical Trials

open access - Editorial

 ....Continuous efforts to improve the validation of surrogate end points are important in several ways. First, the FDA’s accelerated approval program relies on surrogate end points. This program was initiated in 1992 to allow for the earlier approval of drugs that treat serious conditions and that fill a previously unmet medical need on the basis of a surrogate end point. Second, in this era of personalized medicine and rapid development of oncology drugs, many drugs are in the pipeline, waiting for testing in phase III clinical trials. Third, it is difficult, if not impossible, to conduct a phase III trial with OS as the primary end point for a rare disease. Fourth, the current research-funding situation prohibits large trials. Surrogate end points usually allow for smaller trials and shorter completion times and, once validated, could help resolve these issues.

Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: ASCO

open access

Recommendations In addition to estrogen and progesterone receptors and human epidermal growth factor receptor 2, the panel found sufficient evidence of clinical utility for the biomarker assays Oncotype DX, EndoPredict, PAM50, Breast Cancer Index, and urokinase plasminogen activator and plasminogen activator inhibitor type 1 in specific subgroups of breast cancer. No biomarker except for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was found to guide choices of specific treatment regimens. Treatment decisions should also consider disease stage, comorbidities, and patient preferences. 

report/webcast + video (3 min.) Kunle Odunsi (author) Ovarian Cancers: Evolving Paradigms in Research and Care

video

 Kunle Odunsi, MD, PhD, of Roswell Park Cancer Institute in Buffalo, N.Y., co-authored the IOM report. In this exclusive MedPage Today video, Odunsi discusses the key findings, recommendations, and implications of Ovarian Cancers: Evolving Paradigms in Research and Care.

Ovarian Cancers: Evolving Paradigms in Research and Care 

 report
 webcast

Should registered nurses prescribe drugs? - dr vs np vs rn? (poll included)

Healthy Debate - Ontario, Canada

 The Ontario provincial government has said it will expand the scope of practice of registered nurses (RNs) in Ontario to allow them to prescribe medications. Currently, only doctors and nurse practitioners have the ability to prescribe medications. This is a move that could radically change health care – some say for the better, but others are concerned.....

Health care (#1), infrastructure top budget priorities for Canadians: Nanos survey

News
 
Canadians want health care and infrastructure to be the top priorities in the Liberals' first federal budget this spring, according to results of a survey from Nanos Research.
In a survey asking respondents to rank their top two budget priorities, 43 per cent of respondents said health care should be the No. 1 priority in the budget, while 28 per cent said infrastructure spending should be prioritized above all else.....

Mar 4, 2016: Genetics of Breast and Gynecologic Cancers

Health Professional Version - NCI

Sections

• Executive Summary
• Introduction
• Penetrance of Inherited Susceptibility to Hereditary Breast and/​or Gynecologic Cancers
• High-Penetrance Breast and/​or Gynecologic Cancer Susceptibility Genes
• Moderate-Penetrance Genes Associated With Breast and/​or Gynecologic Cancer
• Low-Penetrance Genes and Loci
• Clinical Management of BRCA Mutation Carriers
• Clinical Management of Other Hereditary Breast and/​or Gynecologic Cancer Syndromes
• Psychosocial Issues in Inherited Breast and Ovarian Cancer Syndromes
• Changes to This Summary (03/​04/​2016)
• About This PDQ Summary
• View All Sections

Changes to This Summary (03/04/2016)

 eg.:

The Li-Fraumeni syndrome section was comprehensively reviewed and extensively revised.

Revised text to state that an updated set of operational criteria for the diagnosis of Cowden syndrome based on a systematic literature review has been suggested and is currently utilized in the National Comprehensive Cancer Network (NCCN) guidelines.

Added text to state that despite discordant findings regarding RRSO and breast cancer risk in the existing literature, aggregate data suggest that there is a benefit, although the magnitude of this benefit may not be fully understood. Further prospective studies are needed to confirm these findings.

Whole Genome Sequencing Defines the Genetic Heterogeneity of Familial Pancreatic Cancer

open access

Results

Sample Selection and Sequencing

A total of 638 patients with FPC (Table 1) were selected from 10 registries across North America.....

 Recent advances in sequencing technology provide an unbiased way to search for the genes underlying disease susceptibility (8). Using this approach, PALB2 and ATM were identified as FPC susceptibility genes, together explaining 3% to 5% of FPC cases (8, 9). In a further 8% to 15% of patients with FPC, the increased risk of pancreatic cancer can be attributed to 10 other previously reported FPC susceptibility genes, including BRCA1, BRCA2, CDKN2A, MLH1, MSH2, MSH6, PMS2, PRSS1, STK11, and TP53 (10–16). The genetic basis underlying disease susceptibility in the remaining 80% to 90% of patients with FPC is unknown.

5 tips for fact-checking claims about health

Poynter

 1. Of mice and men
 2. Watch out for conflicts of interest
 3. Don't be tempted by the press release and read beyond the abstract
 4. Beware causal language about observational studies
 5. Learn the difference between relative and absolute risk reduction

Biohype Bibliography - opinion pieces

HealthNewsReview (Bibliography)

Route of hysterectomy & surgical outcomes -a statewide gyn onc population (insurance)

abstract
 Route of hysterectomy and surgical outcomes from a statewide gynecologic oncology population: is there a role for vaginal hysterectomy?

Background

Recent policy changes by insurance companies have been instituted to encourage vaginal hysterectomy (VH) as the preferred route for removal of the uterus. It is not known if advantages of VH for benign indications apply to women with gynecologic cancer.

Conclusion

AH (abdominal hysterectomy) and LH (laparoscopic hysterectomy) remain the preferred routes for hysterectomy in gynecologic oncology. Over the past decade, there has been a significant shift to LH with lower 30-day readmission and complication rates. There may be a limited role for VH (vaginal hysterectomy) in select patients. Current efforts to standardize the surgical approach to hysterectomy should not apply to patients with known or suspected gynecologic cancer.

Surgical outcomes for low volume vs high volume surgeons in Gyn surgery

abstract
Surgical outcomes for low volume versus high volume surgeons in Gynecology surgery: a systematic review and meta-analysis
 

Objective

The aim of this study was to determine the impact of gynecologic surgeon volumes on patient outcomes.

Data Sources

Eligible studies were selected through an electronic literature search from database inception up until September 2015 and references in published studies. Search terms included “surgical volume,” “surgeon volume,” “low-volume OR high-volume,” “gynecology OR hysterectomy OR sling OR pelvic floor repair OR continence procedure”.

Study Eligibility

The literature search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We defined a low volume surgeon (LVS) as one performing the procedure once a month or less and studies were excluded if their definition of LVS was > +/- 33% of our definition. Primary outcomes were total complications, intraoperative complications and postoperative complications.

Study appraisal and synthesis methods: All outcome data for individual studies were entered into Review Manager 5.3 systematic review software. When two or more studies evaluated a designated outcome meta-analysis of the entered data was undertaken as per the Cochrane database methodology. Data analysis was entered into GRADEpro, software, which generated a Summary of Findings (SOF) table that included structured and qualified grading (very low to high) of the quality for the evidence of the individual outcomes and provided a measure of effect.

Results

Fourteen peer-reviewed studies with 741 760 patients were included in the systematic review. For gynecology the low volume surgeon (LVS) group had an increased rate of total complications; OR 1.3, intraoperative complications; OR 1.6  and postoperative complications; OR 1.4 . In gynecologic oncology the LVS group had higher mortality; OR 1.9  In the urogynecology group a single study reported that the LVS group had a higher rate of any complication; RR 1.4 . Another single study found that LVS had higher rates of reoperation for mesh complications after mid-urethral sling procedures; RR 1.4. The evidence is of moderate to very-low quality.

Conclusions

Gynecologists performing procedures approximately once a month or less were found to have higher rates of adverse outcomes in gynecology, gynecologic oncology and urogynecology, with higher mortality in gynecologic oncology.

American Journal of Obstetrics and Gynecology annual meeting 2016

American Journal of Obstetrics and Gynecology (Index only)

 American Journal of Obstetrics and Gynecology

Volume 214, Issue 4, Supplement, Pages A1-A6, S455-S520 (April 2016)

Society of Gynecologic Surgeons 42nd Annual Scientific Meeting, Society of Gynecologic Surgeons 42nd Annual Scientific Meeting
Palm Springs, California
10–13 April 2016

Accelerated geroncogenesis in hereditary breast-ovarian cancer syndrome

open access (in research)

 The geroncogenesis hypothesis postulates that the decline in metabolic cellular health that occurs naturally with aging drives a “field effect” predisposing normal tissues for cancer development.

Population attributable risks of modifiable reproductive factors for breast and ovarian cancers in Korea

open access

(abstract) Background

Breast and ovarian cancers are predominant female cancers with increasing prevalence. The purpose of this study was to estimate the population attributable risks (PARs) of breast and ovarian cancer occurrence based on the relative risks (RRs) of modifiable reproductive factors and population-specific exposure prevalence.

(abstract) Results

The summary PARs for modifiable reproductive factors were 16.7 % (95 % CI 15.8–17.6) for breast cancer (2404 cases) and 81.9 % (95 % CI 55.0–100.0) for ovarian cancer (1579 cases). The modifiable reproductive factors included pregnancy/age at first birth (8.0 %), total period of breastfeeding (3.1 %), oral contraceptive use (5.3 %), and hormone replacement therapy use (0.3 %) for breast cancer and included breastfeeding experience (2.9 %), pregnancy (1.2 %), tubal ligation (24.5 %), and oral contraceptive use (53.3 %) for ovarian cancer.

 

Meta-analysis for estimation of risk for breast and ovarian cancers

To obtain the pooled relative risks (RRs) for the selected risk factors, we conducted a meta-analysis of the results of large-scale, case–control studies in Korea (SeBCS for breast cancer and Ko-Eve for ovarian cancer) and the results from other previous studies. For breast cancer analysis, because the SeBCS included large numbers of cases and matched controls, we restricted the data selection to studies conducted in Korea and did not restrict the study design to reflect Korean risk estimates. For ovarian cancer analysis, given that the Ko-Eve is the only study conducted in Korea, and includes a limited number of cases, we included data from international studies to perform a meta-analysis with Ko-EVE results to obtain stable risk estimates.

Ovarian Cancer A-Z (words associated with ovarian cancer)

Ovarian Cancer Action


Here you will find an index of words associated with ovarian


Here you will find an index of words associated with ovarian cancer

1. A
2. B
3. C
4. D
5. E
6. F
7. G
8. H
9. I
10. J
11. K
12. L
13. M
14. N
15. O
16. P
17. Q
18. R
19. S
20. T
21. U
22. V
23. W
24. X
25. Y
26. Z

Ovarian Cancer Still Gets Shortchanged, National Academy of Medicine Report Finds

NBC News

  Ovarian cancer is being shortchanged in terms of medical attention and understanding, even though it's one of the deadliest cancers there is, experts reported Wednesday.

Book Review: ‘Ending Medical Reversal’ Laments Flip-Flopping (eg. medical whiplash or 'oops')

Blogger's Note: not a recommendation just interesting

The New York Times (2015)

Medical implications of technical accuracy in genome sequencing

open access (Genome Medicine)

Methods

We examine the relationship between human genome complexity and genes/variants reported to be associated with human disease. Specifically, we map regions of medical relevance to benchmark regions of high or low confidence. We use benchmark data to assess the sensitivity and positive predictive value of two representative sequencing pipelines for specific classes of variation.

 In one example of a false positive from our systematic error call set, one sequencing chemistry and one pipeline called a recognized, pathogenic frameshift deletion in BRCA2. Pathogenic variants in the BRCA genes are implicated in hereditary breast and ovarian cancer syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1247/). The variant, rs80359760, is currently categorized in ClinVar as pathogenic/likely pathogenic based on several entries from the Breast Cancer Information Core, the Sharing Clinical Reports Project, and the literature (http://www.ncbi.nlm.nih.gov/clinvar/variation/52831/). Based on GIAB’s consensus sequence, this variant is known to be a false positive call for this patient. However, it might be reported to another patient as an incidental finding, and one with evidence for pathogenicity that might even lead to medical action. Examples like this highlight the importance of confirmatory testing by an orthogonal method. Additionally, we hope that our analyses and the reference materials can provide helpful meta-data for bioinformatics analysis of loci such as these, since this dataset allows positions with systematic biases and medically relevant annotations in public databases to be identified [44, 45].

Molecular Profiling of Clear Cell Ovarian Cancers: Identifying Potential Treatment Targets for Clinical Trials

open access

• Article as PDF (746 KB) - open access

Abstract

Background: Advanced stage/recurrent clear cell ovarian cancers (CCOCs) are characterized by a low response to chemotherapy and a poor prognosis. There is growing interest in investigating novel/molecular targeted therapies in patients with CCOC in histotype-specific trials. However, CCOCs are not a uniform entity and comprise a number of molecular subtypes and it is unlikely that a single approach to treatment will be appropriate for all patients. The aim of this study was to analyze the results of a multiplatform profiling panel in CCOCs to identify potential therapeutic targets.

Patients and Methods: Tumor profiling was performed on 521 CCOCs. They were grouped into pure (n = 422) and mixed (n = 99) CCOC for analysis. Testing included a combination of DNA sequencing (including next-generation sequencing) using a 46-gene panel, immunohistochemistry, fluorescent or chromogenic in situ hybridization, and RNA fragment analysis.

Results: The most common findings were in the PIK3CA/Akt/mTOR pathway, with 61% of all CCOCs showing a molecular alteration in one of these pathway components. Next-generation sequencing revealed PIK3CA mutations in 50% of pure CCOCs. Significant differences were observed between pure and mixed CCOCs with respect to hormone receptor expression (9% vs 34.7% for ER, 13.45 vs 26.4% for PR), cMET (24.1% vs 11.6%), PD-1 tumor infiltrating lymphocytes (48.1% vs 100%), expression of PD-L1 (7.4% vs 25%), and TOPO1 (41% vs 27.1%) on immunohistochemistry, whereas next-generation sequencing revealed significant differences in mutation frequency in PIK3CA (50% vs 18.5%), TP53 (18.1% vs 57.7%), KRAS (12.4% vs 3.7%), and cMET (1.9% vs 11.1%).

Conclusions: This large study confirms that the PIK3CA/Akt/mTOR pathway is commonly altered in CCOCs, and highlights the significant differences between pure and mixed CCOCs. Clear cell ovarian cancers are molecularly heterogeneous and there are a number of potential therapeutic targets which could be tested in clinical trials.

Restaging and Survival Analysis of 4036 Ovarian Cancer Patients According to the 2013 FIGO Classification for Ovarian, Fallopian Tube, and Primary Peritoneal Cancer.

abstract
 

Objective: With the 2013 International Federation of Gynecology and Obstetrics (FIGO) staging for ovarian, fallopian tube, and primary peritoneal cancer, the number of substages changed from 10 to 14. Any classification of a malignancy should easily assign patients to prognostic groups, refer patients to individualized treatments, and allow benchmarking and comparison of patients and results between centers. The stage should reflect survival in particular. The objective of the study was to validate these requirements of the revised FIGO staging on a high number of ovarian cancer patients.

Materials and Methods: Demographic, surgical, histological, and survival data from 4036 ovarian cancer patients were used in the analysis. Five-year survival rates (5YSR) and hazard ratios for the old and revised FIGO staging were calculated using Kaplan-Meier curves and Cox regression.

Results: A total of 1532 patients were assigned to new stages. Stages IA and IC1 had similar survival (5YSR, 87%); and stages IB, IC2, and IC3 had similar survival (5YSR, 75%-80%). Stage IIC was omitted, resulting in similar survival in stages IIA and IIB (5YSR, 61% and 65%). Of 1660 patients in stage IIIC, 79 were restaged: In 16 cases, IIIC was down-staged to IIIA1, as they had only been stage IIIC owing to lymph node metastases; and in 63 cases, IIIC was down-staged to IIIB, as they had lymph node metastases and abdominal tumor of less than 2 cm. The 5YSR in stage IIIC was unchanged (22%). Stage IV (5YSR, 14% ) was restaged as IVA (13%) and IVB (13%). Both were different from IIIC; P < 0.0001.

Conclusion: With introduction of new substages, staging becomes more demanding. Second, as fewer patients are allocated to each substage, statistical power is diminished, resulting in uncertainty in the results. Despite this, and most importantly, the revised coding adequately reflects survival, as there was a clear graphical and statistical tendency for poorer survival with increasing stage.

Managing patients at genetic risk of breast cancer

open access

ABSTRACTHereditary syndromes that increase the risk of breast cancer are not common, but it is critical to recognize and manage them appropriately. This paper reviews the management of patients with the most common hereditary breast cancer syndromes, ie, hereditary breast and ovarian cancer syndrome, hereditary diffuse gastric cancer, Cowden syndrome (PTEN hamartoma tumor syndrome), Peutz-Jeghers syndrome, and Li-Fraumeni syndrome.

KEY POINTS

• In addition to breast cancer, hereditary cancer syndromes increase the risk of other malignancies, with the patterns of malignancy varying by causative genetic mutation.
• Genetic counselors, medical breast specialists, surgical breast specialists, gynecologic oncologists, and others can help, but the primary care provider is the nucleus of the multidisciplinary team.
• Management of these patients often includes surveillance, chemoprevention, and prophylactic surgery.
• All decisions about surveillance, chemoprevention, and surgical risk reduction should be shared with the patient.

With genetic testing becoming more common, primary care physicians need to be familiar with the known syndromes, associated risks, and evidence-based recommendations for management. Here, we review the management of cancer risk in the most common hereditary breast cancer syndromes, ie:

• Hereditary breast and ovarian cancer syndrome⁵
• Hereditary diffuse gastric cancer
• Cowden syndrome (PTEN hamartoma tumor syndrome)
• Peutz-Jeghers syndrome
• Li-Fraumeni syndrome.

 In an earlier article in this journal, Smith and colleagues²¹ reviewed how to recognize heritable breast cancer syndromes. In general, referral for genetic counseling should be considered for patients and their families who have:

• Early-onset breast cancers (before age 50)
• Bilateral breast cancers at any age
• Ovarian cancers at any age
• “Triple-negative” breast cancers (ie, estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor 2-nonamplified (HER2-negative)
• Male breast cancer at any age
• Cancers affecting multiple individuals and in multiple generations.
• Breast, ovarian, pancreatic or prostate cancer in families with Ashkenazi Jewish ancestry

Oncofertility Referral Network - Canada

Cancer Knowledge Network

 Have You Referred a Patient to a Local Fertility Clinic?

Did you know that 45% of oncologists responding to a Canadian survey said they did not know where to refer female cancer patients for a fertility preservation consultation; 70% said they rarely made a referral.

Full disclosure of a cancer diagnosis to a young adult includes providing information about the potential loss of fertility due to cancer treatments.

Oncofertility has emerged as a new interdisciplinary approach to address the reproductive future of young men, women, and children facing a life-preserving but fertility threatening cancer diagnosis. The CKN Oncofertility Referral Network is a nationwide platform that links patients, physicians and fertility clinics to ensure time-sensitive needs are met in providing fertility options for young cancer patients as they embark on treatment.

This network will create a multidisciplinary dialogue between patients and their medical team about fertility sparing options, offering accessible educational information and resources alongside a timely, efficient referral system to fertility specialists.

             Make a Referral                     List of Fertility Clinics

Biomarker tests for molecularly targeted therapies need better evidence, oversight

ScienceDaily

Potentially useful biomarker tests for molecularly targeted therapies are not being adopted appropriately into clinical practice because of a lack of common evidentiary standards necessary for regulatory, reimbursement, and treatment decisions, says a new report.

FULL STORY

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Potentially useful biomarker tests for molecularly targeted therapies are not being adopted appropriately into clinical practice because of a lack of common evidentiary standards necessary for regulatory, reimbursement, and treatment decisions, says a new report by the National Academies of Sciences, Engineering, and Medicine. To enhance patient care and clinical outcomes, the report calls for the creation of a "rapid learning system" that would integrate research on these tests and associated treatments with clinical practice. Appropriate regulatory oversight is also needed to ensure that biomarker tests and targeted therapies are accurate, reliable, and properly validated and implemented.

Biomarker tests for molecularly targeted therapies identify molecular variations specific to an individual patient, which can help determine the most effective therapy for a patient's disease or avoid treatments that could be ineffective or harmful. Advances in research over the past 15 years have led to hundreds of molecularly targeted agents entering the drug development pipeline; numerous biomarker tests and associated therapies have been approved for clinical use in treating cancer and other diseases. However, progress has been hampered by regulatory and reimbursement uncertainties, clinical practice challenges, and limitations in data collection and analysis.
"The timely development of biomarker tests and associated therapies is critical to realizing the full potential of 'precision medicine,'" said Harold L. Moses, chair of the committee that wrote the report, and Ingram Professor of Cancer Research, professor of medicine, pathology, microbiology, and immunology, and chair of the department of cancer biology at Vanderbilt University. "Our report lays out a strategy to ensure that patients have access to effective tests and treatments that are based on solid evidence of their ability to improve health outcomes."....

Advances in Epithelial Ovarian Cancer: Model Systems, Microenvironmental Influences, Therapy, and Origins

open access - ebook 2016 pdf 
(178 pages)

Advances in Epithelial Ovarian Cancer: Model Systems, Microenvironmental Influences, Therapy, and Origins.

 This eBook provides a compendium of the current state-of-the-art in research tools for, and understanding of, the critical research areas in epithelial ovarian cancer (EOC) with a strong emphasis on (HG-SOC). Research areas covered include therapy response and development, microenvironmental influences and the etiology and progression of EOC. Ten articles detail established and novel in vivo and in vitro model systems. These include primary and immortalized cell culture in 2D and 3D as well as genetically engineered, transgenic, spontaneous, syngeneic, classical xenograft and patient derived xenograft mouse models. The generation of genetically engineered mouse models of HG-SOC has been a major dilemma as models with the oncogenic aberrations common in the human malignancy do not accurately recapitulate HG-SOC. Conversely, commonly used HG-SOC cell lines have been found to not harbor the expected genetic changes. These issues as well as the rapid acceptance of patient derived xenograft models are reviewed. Five articles discuss different aspects of the tumor microenvironment including its role in therapy resistance, disease progression and metastasis. Mutation of BRCA1/2 continues to be the best defined risk factor for HG-SOC. Three articles discuss BRCA-loss in the context of disease development, targeted therapies and changes in preventative measures proposed for mutation carriers in light of the recent advances in knowledge regarding the origins of this malignancy. An image of HG-SOC with reduced BRCA1 expression is featured on the cover (image by VM Howell). A major clinical issue for patients with HG-SOC is the development of therapy resistance. Five articles focus on therapy resistance and different ways to overcome resistance. Overall, this eBook is an outstanding resource to aid researchers design their programs of research and determine the most appropriate and up-to-date EOC model systems to address their research questions.