UBC Conference notice: Contested Ground: Why Are Some Policies Healthy and Others Not?

Conference 

Why Are Some Policies Healthy and Others Not?

CHSPR’s 28th annual health policy conference, April 5-6, 2016, in Vancouver, will celebrate the career of Canada’s Undisciplined Economist, and our very own, Robert G. Evans.

Why is it so difficult to improve our health care system? Good policy ideas abound. Unfortunately all such ideas create winners and losers, such that health care policy is always intensely “Contested Ground”. Potential losers are frequently in a position to block or subvert progress because those who stand to lose are concentrated and strategically placed, while the beneficiaries are diffuse and disorganized. This conference will explore why some policies are “healthy” and others not. Some survive the contest, while others, although potentially also contributing to a more effective and efficient health care system, and/or improving a population’s health, don’t. Still others, with well-understood unhealthy effects, thrive like weeds.

Bob Evans has spent his career exposing “inconvenient truths” about the impacts of interests, positions, and policies in the health realm. The conference, intended to celebrate the vision, contributions and impacts of that body of work, will feature speakers addressing some of Bob’s most visible lifetime preoccupations. Conference themes will include international perspectives on contemporary Canadian health policy challenges, health care financing, other current health policy issues such as legal challenges, and the role of broader health determinants.

Follow @CHSPR on Twitter for conference updates and use #CHSPR2016 to share your thoughts before and during the event.

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Overview

Program

Speakers

Venue

Registration

Abstracts

Sponsors

Invited Commentary: The Neoadjuvant Model and Complete Pathologic Response in Breast Cancer: All or Nothing?

Blogger's Comment: although not specific to ovarian cancer neoadjuvant therapy is relevant plus appropriate for those with dual primaries

JAMA  (abstract plus 1st page view - full access requires $$)

Invited Commentary: Response Rate as an Approval End Point in Oncology: Back to the Future

JAMA (part comments plus page 1 - full access requires $$)

Overall response rate (ORR) as a surrogate end point in oncology drug approval has a long history. In the 1970s, the US Food and Drug Administration (FDA) usually approved drugs on the basis of ORR. In the 1980s, after discussions with the Oncologic Drug Advisory Committee, the FDA determined that cancer drug approval should be based on more direct evidence of clinical benefit, such as improvements in overall survival (OS), tumor-related symptoms, or physical function.1 In the past decade, due to an improved understanding of the genomic underpinnings of cancer, better molecular characterization of tumors, and more precisely targeted agents, unprecedented rates of response have radically altered the therapeutic landscape in a number of malignant neoplasms. Therefore, ORR and duration of response as assessed in single-arm trials has served as the basis of accelerated approval and at times regular approval in a number of refractory malignant neoplasms, including non–small-cell lung cancer (NSCLC), lymphoma, melanoma, and myeloma.

Response Rate as a Regulatory End Point in Single-Arm Studies of Advanced Solid Tumors

(Abstract) JAMA

Importance  Objective response rate (ORR) is an increasingly important end point for accelerated development of highly active anticancer therapies, yet its relationship to regulatory approval is not well characterized.

Objective  To identify circumstances in which a high ORR is associated with regulatory approval, and therefore might be an appropriate end point for definitive single-arm studies of anticancer therapies.

Data Source  A database of all oncology clinical trials registered at clinicaltrials.gov between October 1, 2007, and September 30, 2010.

Study Selection  Trials of palliative systemic therapies for 4 measurable solid tumor types, limited to those with trial arms of at least 20 patients reporting ORR per Response Evaluation Criteria in Solid Tumors (RECIST).

Data Extraction and Synthesis  A systematic search was used to identify the reported ORR for each eligible treatment arm that had been presented publicly.

Main Outcomes and Measures  For each treatment regimen, defined as a single-agent or unique combination of agents for 1 cancer type, the mean ORR and the maximum ORR statistically exceeded were calculated, and their association with regulatory approval was studied. A regimen was considered approved for a specific cancer type if it had received regulatory approval in any country for treatment of advanced cancer of that type.

Results  From 1800 trials, 874 eligible trial arms in 578 eligible trials were identified; 542 arms had ORR data available for 294 regimens. Maximum ORR and mean ORR were significantly associated with regulatory approval (τ = 0.27, P < .001; τ = 0.12, P = .01); this relationship was stronger for single-agent therapies (τ = 0.49; τ = 0.41) than for combination regimens (τ = 0.28; τ = 0.17). Evaluation of ORR thresholds between 20% and 60% as potential trial end points demonstrated that ORR statistically exceeding 30% with a single agent had 98% specificity and 89% positive predictive value for identifying regimens achieving regulatory approval.

Conclusions and Relevance  For single-agent regimens, high ORR was associated with regulatory approval; this relationship was less strong for combination regimens. Our data suggest that high ORR (eg, statistically exceeding an ORR of 30%) is an appropriate end point for single-arm trials aiming to demonstrate breakthrough activity of a single-agent anticancer therapy.

JAMA Oncology: The Ethical Imperative of Healthy Paternalism in Advance Directive Discussions at the End of Life

JAMA Viewpoint (open access)

CONCLUSIONS

We believe that the time is right to assert the ethical imperatives of a healthy paternalism in discussions regarding advance directives with patients with cancer. Given the widely held perception that the principle of autonomy requires withholding prognostication and advice during discussions on advance directives, additional research and educational interventions among physicians in training and practice are required to address this issue, which has major implications for both quality of care and cost-effectiveness. In these vital conversations with patients, a studied neutrality regarding outcomes of CPR should not be an option. Oncologists must lead the way in this regard and document these discussions in the medical record for the benefit of all medical caregivers. The false dichotomy between healthy paternalism and patient autonomy should be abandoned on ethical premises and in the interest of patients and society.

2016 SGO Annual Meeting on Women's Cancer®: Late Breaking Abstracts

2016 Annual Meeting (SGO)

BRAFV600E mutations in serous ovarian cancer and response to the BRAF inhibitor dabrafenib.

Abstract

....These results demonstrate that molecular analysis of low-grade serous ovarian carcinoma can identify targetable mutations and provide effective treatment options. The substantial response to dabrafenib suggests that BRAF inhibition represents a potential therapeutic option for ovarian cancer patients with somaticBRAF^V600E mutations and should be tested in future trials. However, the results also highlight the need for novel clinical trial design, as traditional clinical trials are unlikely to be effective in such rare ovarian cancer sub-groups.

Molecular characterization of mucinous ovarian carcinoma

Abstract

Mucinous ovarian carcinoma (MOC) is a rare, chemoresistant tumor known to share pathologic features with tumors of the gastrointestinal and pancreaticobiliary tracts. To better understand the genomic and proteomic landscapes of invasive MOCs, we identified somatic mutations and proteins expression in a single institution cohort and compared these results with data from TCGA tumor projects.

Twenty-six tumors consistent with primary invasive MOC after expert pathology review and with available paired tumor and normal tissue were identified from institutional databases between July 2001 and July 2012. DNA extracted from FFPE or fresh frozen samples underwent next generation sequencing with a combination of a candidate gene assay (37 genes), the MSK-IMPACT assay (341 genes), transcriptome sequencing, and whole exome sequencing. Copy number alterations were identified using data from the MSK-IMPACT assay, whole exome sequencing or Affymetrix SNP 6.0 arrays. Immunohistochemistry (IHC) was performed using optimized antibodies for six proteins to confirm the diagnosis of MOC (ER, PR, CK7, CK20, CDX-2, PAX8) and seven proteins to correlate with mutation status and copy number alterations (p53, ARID1A[Baf250a], PTEN, PMS2, MSH6, HER2, p16). Mutation data for other TCGA tumor types was obtained from the cBio Cancer Genomics Portal (cbioportal.org).

The median age of the cohort was 58 years (range 20-86 years). Most (19/26, 73%) of the tumors were stage I. Somatic TP53 and KRAS mutations were the most common seen and were identified in 18 (69%) cases each, with a co-mutation rate of 50% (13/26). Other commonly mutated genes include ARID1A,PTEN, and PIK3CA. Homozygous deletions of CDKN2A were found in 27% (7/26). ERBB2 alterations were identified in 19% (5/26) and consisted of three amplifications and two mutations. Mutations in at least one potentially targetable gene were identified in 42% (11/26) of tumors. IHC was concordant with sequencing results in 154/182 (85%) of stained cases. Pancreatic, colorectal, lung adenocarcinoma, endometrial, and stomach cancers have the highest frequency of KRAS mutations. Co-mutations of KRAS and TP53 occur most commonly in pancreatic (59%) and colorectal (21%) carcinomas. CDKN2Ahomozygous deletions are also found at a similar frequency in pancreatic adenocarcinomas (28%). When evaluating the mutation rates of the five most commonly mutated genes in our MOC cohort with colorectal, pancreatic, gastric and high-grade serous ovarian carcinomas (HGSOC) in the TCGA datasets, pancreatic adenocarcinoma showed the most similarity. HGSOC showed little similarity to the MOCs.

KRAS and TP53 co-mutation are common in invasive MOCs. Other commonly mutated genes include ARID1A, PTEN, and PIK3CA. Potentially targetableERBB2 alterations were identified in several cases. Despite anatomic distinctions, the mutational landscape of MOC shares similarities with that of pancreatic adenocarcinoma including frequent CDKN2A deletions andKRAS/TP53 co-mutation. The suggested shared molecular pattern with pancreatic adenocarcinoma offers potential to guide future developmental therapeutics.

Meeting Reminder: Experiences of Primary Care Physicians in 11 Countries

Meeting Registration

Details

• Date:Tue, Mar 1, 2016
• Time:12:30 PM EST
• Duration:1 hour 30 minutes
• Host(s):The Commonwealth Fund

• Meeting Description:

  This webinar will feature key findings from The Commonwealth Fund’s latest International Health Policy Survey, as well as commentary and perspective from experts in the Netherlands and the United Kingdom. Published in Health Affairs in December, the survey compared the views and experiences of primary care physicians in 11 countries—Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, the United Kingdom, and the United States—with respect to preparedness to manage patients with complex conditions, practice capacity to provide access and chronic care management, experiences in coordinating care, and more. 

Clinical Trials in Precision Oncology

abstract

BACKGROUND: Availability of genomic information used in the management of cancer treatment has outpaced both regulatory and reimbursement efforts. Many types of clinical trials are underway to validate the utility of emerging genome-based biomarkers for diagnostic, prognostic, and predictive applications. Clinical trials are a key source of evidence required for US Food and Drug Administration approval of therapies and companion diagnostics and for establishing the acceptance criteria for reimbursement.

CONTENT: Determining the eligibility of patients for molecular-based clinical trials and the interpretation of data emerging from clinical trials is significantly hampered by 2 primary factors: the lack of specific reporting standards for biomarkers in clinical trials and the lack of adherence to official gene and variant naming standards. Clinical trial registries need specifics on the mutation required for enrollment as opposed to allowing a generic mutation entry such as, “EGFRmutation.”

Annual Meeting Special Interest Sessions | SGO

Special Interest Sessions

 Special Interest Sessions
Preconference Special Interest Session I: Mastering Billing and Coding For Gyn Oncology in 2016
Preconference Special Interest Session II: Contemporary Issues in Gynecologic Oncology: An International Focus
Preconference Special Interest Session III: A Brief History of Time: Landmark Trials and Future Directions
Preconference Special Interest Session IV: Practicing Wellness: Tools for Cultivating Resilience and Avoiding Burnout
Special Interest Session V: Proactive Screening for High-Risk Women in Gynecologic Oncology (Allied)

The influence of health-specific social network site (Facebook) use on the psychological well-being of (ovarian) cancer-affected people

abstract
 

OBJECTIVE:

We aimed to explore and examine how and in what ways the use of social network sites (SNSs) can improve health outcomes, specifically better psychological well-being, for cancer-affected people.

METHODS:

Qualitative semi-structured interviews were conducted with users of the Ovarian Cancer Australia Facebook page (OCA Facebook), the exemplar SNS used in this study. Twenty-five women affected by ovarian cancer who were users of OCA Facebook were interviewed. A multi-theory perspective was employed to interpret the data.

RESULTS:

Most of the study participants used OCA Facebook daily. Some users were passive and only observed created content, while other users actively posted content and communicated with other members. Analysis showed that the use of this SNS enhanced social support for users, improved the users' experiences of social connectedness, and helped users learn and develop social presence, which ultimately improved their psychological well-being.

DISCUSSION:

The strong theoretical underpinning of our research and empirically derived results led to a new understanding of the capacity of SNSs to improve psychological well-being. Our study provides evidence showing how the integration of these tools into existing health services can enhance patients' psychological well-being. This study also contributes to the body of knowledge on the implications of SNS use for improving the psychological well-being of cancer-affected people.

CONCLUSION:

This research assessed the relationship between the use of SNSs, specifically OCA Facebook, and the psychological well-being of cancer-affected people. The study confirmed that using OCA Facebook can improve psychological well-being by demonstrating the potential value of SNSs as a support service in the healthcare industry.

Talc Powder and Ovarian Cancer: What's the Science?

Medscape

 The fact that talc is even being questioned as an ovarian cancer risk may surprise some professionals, said Daniel Cramer, MD, ScD, an obstetrician/gynecologist at Brigham and Women's Hospital and Harvard Medical School in Boston and a prominent researcher in this field.

"Some clinicians — even some gynaecologists — will never have heard of this association," he told Medscape Medical News. "I've had clinicians say to me, 'Talc? Do they still sell it?'"

Editors' Recommendations

• J&J Must Pay $72 Million in Talc Powder-Ovarian Cancer Case
• Talc Use in Genital Area Linked to Ovarian Cancer

Feb 25, 2016: Weekly vs. Every-3-Week Paclitaxel and Carboplatin for Ovarian Cancer

NEJM

 

Review: The effectiveness and cost-effectiveness of erythropoiesis-stimulating agents (epoetin and darbepoetin) for treating cancer treatment-induced anaemia....

Journal: Health Technology Assessment Volume: 20 Issue: 13
Publication date: February 2016
DOI: http://dx.doi.org/10.3310/hta20130

 The effectiveness and cost-effectiveness of erythropoiesis-stimulating agents (epoetin and darbepoetin) for treating cancer treatment-induced anaemia (including review of technology appraisal no. 142): a systematic review and economic model

 Plain English summary

Anaemia is a common side effect of cancer treatments and can lead to a reduction in quality of life. Erythropoiesis-stimulating agents (ESAs) are licensed for use in conjunction with red blood cell transfusions to improve cancer treatment-induced anaemia. To assess the effectiveness and cost-effectiveness of ESAs for the treatment of anaemia in cancer patients, a systematic review of clinical effectiveness and an economic evaluation were conducted. Twenty-three ESA studies with starting doses according to European labelling regulations were included in the review. Data suggest that there is clinical benefit from ESAs for anaemia-related outcomes and an improvement in health-related quality-of-life scores. The impact of ESAs on adverse events and survival remains highly uncertain. Base-case incremental cost-effectiveness ratios (ICERs) for ESA treatment compared with no ESA treatment ranged from £19,429 to £35,018 per quality-adjusted life-year gained, but sensitivity and scenario analyses demonstrate considerable uncertainty in these ICERs, including the possibility of overall health disadvantages. All ICERs were sensitive to survival and cost. ESAs could be cost-effective when used closer to licence, but there is considerable uncertainty, mainly because of unknown impacts on survival.

Evidence on talc cancer risk differs for jurors, researchers

Reuters

Grass-Fed Beef and Wild Fish: Hype or Healthy Choices?

Insight
 
Learn more:

• Debunking Common Nutrition Myths
• What Should I Eat During Cancer Treatment?
• Does Sugar Feed Cancer?

Let Canadians plan ahead for doctor-assisted death, report advises (report)- Politics - Canada

CBC News

 Read the report of the assisted-dying committee (pdf)

• Read the report of the assisted-dying committee (pdf)
• THE CURRENT | Doctor-assisted death and children
• Assisted death legislation and psychological suffering
• Let people opt for assisted death while still competent: group
• Only Ontario, Quebec have interim guidelines ready

(2) Specific gene patterns and molecular pathways related to human carcinogenesis in different populations among various geographic locations

1. Correspondence

   1. Reply to specific gene patterns and molecular pathways related to human carcinogenesis in different populations among various geographic locations
      

      • requires $$ to view
   2. Specific gene patterns and molecular pathways related to human carcinogenesis in different populations among various geographic locations
      

      • Abstract

Unconventional treatment strategy controls -- rather than eradicates

 ScienceDaily

Evidence on talc cancer risk differs for jurors, researchers - media

Reuters

Unifying all of Europe in clinical trial participation: the ECRAN project

On Medicine

 
http://www.ecranproject.eu/

Preparing to Launch the Precision Medicine Initiative Cohort Program (U.S.)

(NIH)

Warning issued about cancer pill sold online; could release cyanide when ingested

media

 

Beyond the dose-limiting toxicity period: Dermatologic adverse events of patients on phase 1 trials...

abstract
  Beyond the dose-limiting toxicity period: Dermatologic adverse events of patients on phase 1 trials of the Cancer Therapeutics Evaluation Program

BACKGROUND

Dermatologic adverse events (AEs) can be key determinants of overall drug tolerability and of the maximum tolerated and recommended phase 2 doses in phase 1 trials. The authors present the largest dedicated analysis of dermatologic AEs on phase 1 trials to date.

METHODS

Data from a prospectively maintained database of patients with solid tumors who were enrolled onto Cancer Therapeutics Evaluation Program (CTEP)-sponsored phase 1 trials of cytotoxic or molecularly targeted agents (MTAs) from 2000 to 2010 were analyzed. Cumulative incidence, site, and type of drug-related dermatologic AEs were described and compared. The timing of worst drug-related dermatologic AEs was summarized.

RESULTS

In total, 3517 patients with solid tumors and 6165 unique, drug-related dermatologic AEs were analyzed, including 1545 patients on MTA-only trials, 671 on cytotoxic-only trials, and 1392 on combination MTA and cytotoxic trials. Of 1270 patients who had drug-related dermatologic events, the timing of the worst AE was as follows: 743 (cycle 1), 303 (cycle 2), and 224 (cycle 3 or later). Although the cumulative incidence of grade ≥3 drug-related AEs increased to 2.4% by cycle 6, it was only 1.6% at the end of cycle 1. The cumulative incidence of drug-related AEs was highest in patients who received MTA-only therapy (P < .001) and differed by dose level (P  < .001). In patients who received MTA-only therapy, drug-related AEs were most common for combination kinase inhibitor-containing therapy (P < .001).

CONCLUSIONS

A substantial proportion of drug-related dermatologic AEs occur after the traditional dose-limiting toxicity monitoring period of phase 1 clinical trials. Future designs should account for late toxicities.

 

“Invisible work” toll among family and unpaid caregivers

NIH
 At a Glance

• Unpaid caregivers who helped with the health care of older adults experienced emotional, physical, and financial difficulties, as well as lower work productivity.
• The findings provide a better understanding of the unmet needs and challenges of this often invisible workforce, which plays a key role in the health care system.

Index : International Journal of Gynecological Cancer

Index

Impersonating a doctor is hard; becoming a healer is easy

statnews

 Stephen Barrett, MD, writes about dubious health and nutrition practices at Quackwatch, Credential Watch, and 23 other consumer-protection websites he has founded and publishes a free weekly newsletter.

Coming soon: Cochrane Crowd

Coming soon: Cochrane Crowd

 We are very excited to announce that Cochrane Crowd, Cochrane’s new citizen science platform, is coming soon. Cochrane Crowd contributors will help identify the research we need to produce quality health evidence.
 

call for nominations: Masterclass on the Conduct and Use of Patient-Oriented Research

Ontario, Canada

The masterclass is designed to prepare future champions for the conduct and use of patient-oriented research in Ontario’s health system and future mentors to others becoming involved in the conduct and use of patient-oriented research.

Funders and contributing partners
The masterclass is supported by the Ontario SPOR SUPPORT Unit (OSSU) with funding from the Government of Ontario and the Canadian Institutes of Health Research (CIHR).  The design of the masterclass curriculum and coordination of the faculty involved in its execution are being led by the McMaster Health Forum in partnership with the Institute for Health Policy, Management and Evaluation at the University of Toronto and the Ottawa Hospital Research Institute.

Objectives

• To develop the competencies needed to support the conduct and use patient-oriented research in Ontario
• To become familiar with the additional training and other supports available in Ontario to conduct and use patient-oriented research
• To identify ways that you, your organization and other organizations with whom you work can better support the conduct and use of patient-oriented research in the future and monitor and evaluate your efforts

Selected nominees will receive an invitation to participate, with priority given to those who:

• have an emerging or strong interest in patient-oriented research
• have experience as one of:
  • patient or family member of a patient who has received care in Ontario’s health system,
  • healthcare provider who participates in or uses (or would like to use) patient-oriented research in their clinical practice,
  • policymaker or manager who supports (or would like to support) patient-oriented research or uses it in their decision-making, or
  • researcher or research trainee who conducts (or would like to conduct) patient-oriented research
• have qualities that make them well suited to, and likely to commit to, act as champions for patient-oriented research and, when possible, to mentor others becoming involved in the conduct and use of patient-oriented research
• contribute to the diversity of the participants by virtue of the part of the province where they’re from or their gender, first language, ethnocultural background, age (or career stage), patient-engagement experience, and focus/interest.

Doctor discusses talcum cancer risk (ovarian cancer) - video including comment on WHO

video (after the commercials)

Doctor discusses talcum cancer risk

News

February 24, 2016

06:08

Dr. Daniel Cramer  (Boston) discusses his research into a possible link between over the counter talcum powder and an increasing risk of ovarian cancer in women

Johnson & Johnson ordered to pay $72M to family in (ovarian) cancer-talcum powder case

media including public comments
 Johnson & Johnson ordered to pay $72M to family in cancer-talcum powder case

Civil suit part of a broader claim in St. Louis court involving dozens of people
 

WHO says 'limited evidence' in humans

Spokeswoman Carol Goodrich said Tuesday that the New Jersey-based company was considering its next legal move.
In a written statement, she said the decision "goes against decades of sound science proving the safety of talc as a cosmetic ingredient in multiple products," citing supportive research by the U.S. Food and Drug Administration and National Cancer Institute.....

 

Talcum powder-cancer link questioned

Nora Freeman Engstrom, a Stanford University law professor not involved in the Missouri case, said it's unlikely the $72-million award will survive, noting that the U.S. Supreme Court, in a recent series of rulings, has maintained that appellate courts clamp down on punitive damages....

Hereditary Syndromes Manifesting as Endometrial Carcinoma: How Can Pathological Features Aid Risk Assessment?

open access

2) Histological Evaluation. Endometrial carcinomas associated with LS have been shown to exhibit a tendency to occur in the lower uterine segment (LUS) with up to third of such tumors attributed to this syndrome [38]. Histologically, LS-associated tumors have a diverse morphological appearance. The most common subtype is endometrioid carcinoma but serous carcinoma, clear cell carcinoma, and carcinosarcoma are also well accounted for [39]. Nonendometrioid carcinomas such as clear cell carcinoma, serous cell carcinoma, and carcinosarcoma are known to occur in LS patients at a younger age than is commonly seen in non-LS patients [40]. There is also a well-documented predisposition for LS-associated tumors to exhibit high grade features with a mixed histology which can at times represent a huge challenge to anatomic pathologists attempting to subtype the tumor components into the various neat categorical variants [41, 42]. Difficulty in separating the various tumor components comprising endometrioid, serous, and/or clear cell carcinomas is not uncommon in such situations [42]. Interestingly, tumors seen arising in the LUS have been shown to occasionally disclose histological and immunohistochemical features which are difficult to ascertain if the tumor is an endometrial or endocervical primary adenocarcinoma [38].

 Table 1: A summary of the epidemiological, mutational, clinical, and pathological characteristics and features encountered in hereditary syndromes manifesting as endometrial carcinoma. The indicators noted by pathologists to augur a need to notify clinicians on the possible need for referral to a geneticist for further clinical assessment and confirmatory gene mutational testing. Highlighted in the extreme right column are the histological features seen on microscopy and ancillary tests including immunohistochemistry and polymerase chain reaction- (PCR-) based tests such as microsatellite instability analysis and MLH-1 methylation study.

Prioritizing Variants in Complete Hereditary Breast and Ovarian Cancer (HBOC) Genes in Patients Lacking known BRCA Mutations (+ Lynch syndrome genes)

abstract

BRCA1 and BRCA2 testing for Hereditary breast and ovarian cancer (HBOC) does not identify all pathogenic variants. Sequencing of 20 complete genes in HBOC patients with uninformative test results (N = 287), including non-coding and flanking sequences of ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, EPCAM, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD51B, STK11, TP53, and XRCC2, identified 38,372 unique variants. We apply information theory (IT) to predict and prioritize non-coding variants of uncertain significance (VUS) in regulatory, coding, and intronic regions based on changes in binding sites in these genes. Besides mRNA splicing, IT provides a common framework to evaluate potential affinity changes in transcription factor (TFBSs), splicing regulatory (SRBSs), and RNA-binding protein (RBBSs) binding sites following mutation. We prioritized variants affecting the strengths of 10 splice sites (4 natural, 6 cryptic), 148 SRBS, 36 TFBS, and 31 RBBS. Three variants were also prioritized based on their predicted effects on mRNA secondary (2°) structure, and 17 for pseudoexon activation. Additionally, 4 frameshift, 2 in-frame deletions, and 5 stop-gain mutations were identified. When combined with pedigree information, complete gene sequence analysis can focus attention on a limited set of variants in a wide spectrum of functional mutation types for downstream functional and co-segregation analysis. 

Ovarian Low-grade Serous Carcinoma: A Clinicopathologic Study of 33 Cases With Primary Surgery Performed at a Single Institution. - PubMed - NCBI

abstract

 Ovarian low-grade serous carcinoma (LGSC) is an entity with distinct pathologic and clinical features. The number of studies on this type of tumor is limited. In this article, we present our experience with 33 cases of ovarian LGSC with primary surgical treatment at our institution. For comparison, a cohort of ovarian high-grade serous carcinoma (HGSC) was also studied. Clinical information was obtained from the patients' charts or from the treating physicians. Hematoxylin and eosin slides were reviewed of 28 available LGSCs, and the following parameters were recorded: presence/absence of a serous borderline tumor (SBT), presence/absence of micropapillary/cribriform pattern (MP/CP), architectural pattern in the invasive component, and presence/absence of desmoplasia or fibrosis. The incidence of ovarian LGSC was 4.7%. LGSC patients ranged in age from 19 to 79 years (mean, 52 y), with 21.2% younger than 40 years. HGSC patients ranged in age from 38 to 90 years (mean, 62 y), with 1.6% younger than 40 years. LGSCs were staged as follows: stage I (2), stage III (23), and stage IV (8). Twenty-eight of 33 LGSC cases had concurrent SBT,

New insights into the role of gender in breast cancer development (eg. BRCA2)

New insights 

 One of the most interesting findings was that MBCs diagnosed in BRCA2 mutation carriers were more likely to be of a higher grade at younger ages than breast cancers diagnosed in men from the general population. Why having a mutation in BRCA2 would differ in the presentation between MBC and FBC is a mystery.

What makes research worth the effort? Inconsistencies between clinical trial protocols and the published results

blog - research

Feb 2016: Immunotherapy in Ovarian Cancer—Where Are We Going? (Markman)

open access

@OncEd Presents Dr. Allan Covens - BRCA Mutations in Ovarian Cancer - 2015

oncologytube

Creighton's 'tenacious' Dr. Lynch – who once lectured while lying on a gurney – honored for cancer research - Health

Health
 

Decades ago Lynch was a pioneer of the concept that some cancers had hereditary causes. Physicians on Monday said Lynch initially was scorned for the notion. “People didn’t believe him,” said Dr. Peter Silberstein, chief of oncology at Creighton.

Discovery of candidate tumor biomarkers for treatment with intraperitoneal chemotherapy for ovarian cancer

open access
 

1. Abstract
2. Introduction
3. Methods
4. Results
5. Discussion
6. Additional Information
7. References
8. Acknowledgements
9. Author information
10. Supplementary information
11. Comments

Single Gene Prognostic Biomarkers in (serous) Ovarian Cancer: A Meta-Analysis

open access

Abstract

Purpose

To discover novel prognostic biomarkers in ovarian serous carcinomas.

Methods

A meta-analysis of all single genes probes in the TCGA and HAS ovarian cohorts was performed to identify possible biomarkers using Cox regression as a continuous variable for overall survival....

Results

Twelve genes with high mRNA expression were prognostic of poor outcome with an FDR <.05 (AXL, APC, RAB11FIP5, C19orf2, CYBRD1, PINK1, LRRN3, AQP1, DES, XRCC4, BCHE, and ASAP3). Twenty genes with low mRNA expression were prognostic of poor outcome with an FDR <.05 (LRIG1, SLC33A1, NUCB2, POLD3, ESR2, GOLPH3, XBP1, PAXIP1, CYB561, POLA2, CDH1, GMNN, SLC37A4, FAM174B, AGR2, SDR39U1, MAGT1, GJB1, SDF2L1, and C9orf82).

Conclusion

A meta-analysis of all single genes identified thirty-two candidate biomarkers for their possible role in ovarian serous carcinoma. These genes can provide insight into the drivers or regulators of ovarian cancer and should be evaluated in future studies. Genes with high expression indicating poor outcome are possible therapeutic targets with known antagonists or inhibitors. Additionally, the genes could be combined into a prognostic multi-gene signature and tested in future ovarian cohorts.

Introduction

We sought to identify single-gene prognostic biomarkers using meta-analysis of publicly available mRNA expression data from ovarian cohorts with known drug-gene interactions that could be potentially used to indicate alternative treatment strategies.

Cutaneous markers of internal malignancy, skin signs of cancer

DermNet NZ

Seminars in Oncology: Cutaneous (skin) Manifestations in (selected) cancers

abstract(s) 
 

Cutaneous Manifestations of Breast Cancer

Cutaneous Manifestations of Genito-Urinary Malignancy

Cutaneous Manifestations of Lung Cancer

Varied Skin Manifestations of Malignancy: Critical Clues in Diagnosis and TreatmentSkin Manifestations Associated with Kidney Cancer

Cutaneous Manifestations Associated with Melanoma

The Cutaneous Manifestations of Gastrointestinal Malignancy

Soft Tissue Sarcomas in Skin: Presentations and Management

Skin Manifestations of Endocrine and Neuroendocrine Tumors

Cutaneous Manifestations of Non-Targeted and Targeted Chemotherapies

Cutaneous Manifestations of Multiple Myeloma and Other Plasma Cell Proliferative Disorders

Partnering with Skin to Outsmart Cancer: Following Leads Provided by Tumor-Specific T Cells

Cutaneous Manifestations in Neuro-Oncology: Clinically Relevant Tumor and Treatment Associated Dermatologic Findings

Cutaneous Manifestations and Management of Hematologic Neoplasms
Cutaneous Squamous Cell Carcinomas in Solid Organ Transplant Recipients: Emerging Strategies for Surveillance, Staging, and Treatment

Painful Hands and Feet After Cancer Treatment: Inflammation Affecting the Mind-Body Connection

open access: Editorial

 With the growing number of cancer survivors, it is critical for us to consider toxicities that arise during treatment and do not resolve after treatment ends. Some symptoms continue to burden patients for many years after the cancer has been cured, and chemotherapy-induced peripheral neuropathy (CIPN) is a conspicuous example. CIPN has taken on considerable prominence in the past decade with the more widespread use of the vinca alkaloids, taxanes, platinum analogs, and bortezomib, with an overall incidence estimated at 38%.^1,2 Unfortunately, CIPN has been resistant to multiple strategies aimed at its prevention or treatment once established.^1,3 A critical step in the development of new approaches to management of a cancer treatment–related symptom is to have a better understanding of the mechanism(s) associated with its development, and/or identification of those individuals who are at particularly high risk for experiencing the symptom or having persistent difficulties.^4-7 We are fortunate that there is increasing research interest in symptom science, and the paper by Nudelman et al^{8 (in breast cancer patients)} that accompanies this editorial is an example of this type of work....

 We must be clinically attuned to the complaints our patients voice, and we must make a serious effort to develop prevention and treatment strategies that will reduce the burden of cancer treatment–associated toxicities.

 REFERENCES

1. 1.↵
   1. Hershman DL,
   2. Lacchetti C,
   3. Dworkin RH,
   4. et al.,
   5. American Society of Clinical Oncology

   (2014) Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 32:1941–1967.

   Abstract/FREE Full Text
2. 2.↵
   1. Seretny M,
   2. Currie GL,
   3. Sena ES,
   4. et al.

   (2014) Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis. Pain 155:2461–2470.

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news: California Pacific Medical Center Shows New Strategy for Treating Ovarian Cancer Provides Survival Benefits with Fewer Side Effects

press release

 The open-label, phase 3 randomized study was conducted by researchers at Sutter Health’s California Pacific Medical Center (CPMC) and leading cancer centers across the U.S., and suggests new strategies for personalized treatments.

 “No previous studies assessed the weekly administration of paclitaxel with bevacizumab, to target angiogenesis,” said Dr. Chan. “Moreover, there has been little research into how taxanes may have differing effects depending on the concurrent administration of bevacizumab.”

 In the study, 692 women with newly diagnosed stage II-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer who had received no prior treatment were prospectively stratified by whether they elected to receive bevacizumab, and then randomly allocated to receive either paclitaxel every three weeks plus carboplatin, or weekly paclitaxel plus carboplatin. The primary study endpoint was PFS.

Retraction Note to: KDM3A confers metastasis and chemoresistance in epithelial ovarian cancer

Retraction Note

Retraction Note to: J Mol Hist (2015) 46:511–518 DOI 10.1007/s10735-015-9642-3

This article has been retracted at the request of the authors. The Editor-in-Chief has decided to retract this article, and the Publisher supports the decision of the Editor-in-Chief. This article has been found to contain plagiarized materials. Unpublished data were obtained from an unnamed source and have been used without permission. The owner of the data does not wish to be named in this retraction notice.