OVARIAN CANCER and US

Blog Archives: Nov 2004 - present

#ovariancancers



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Saturday, July 23, 2016

Gynecologic Oncology journal Index (August 2016)



Gynecologic Oncology

Editorial: Precision oncology: a strategy we were not ready to deploy



open access (pdf)

Video-assisted genetic counseling in patients with ovarian, fallopian and peritoneal carcinoma (Tennessee)



abstract

Highlights

  • A new method of genetic counseling for ovarian cancer patients is proposed.
  • Patients were shown a genetic counseling video and offered immediate testing.
  • A significantly larger proportion of patients were tested using this new algorithm.

Objectives

To compare the proportion of patients with ovarian, fallopian or peritoneal carcinoma who receive genetic testing after observing a genetic counseling video versus after traditional referral for genetic counseling and testing at physician discretion.

Methods

A retrospective chart review was performed of all patients seen at the West Cancer Center for evaluation of ovarian, fallopian or peritoneal carcinoma from 7/2014 to 8/2015. Patients seen between 7/2014 and 12/2014 were offered standard genetic counseling. We adopted a new standard of care from 3/2015 to 8/2015 involving the use of a genetic counseling video on a digital tablet. The video was shown to patients with ovarian, fallopian or peritoneal cancer, who were then given the option to undergo genetic testing at the end of the viewing. We compared the number and proportion of patients who received genetic testing in both groups.

Results

The initial group of 267 patients received referral and te\sting at the physician's discretion between 8/2014 and 12/2014. 77/267 (29%) of these patients underwent genetic testing. 295 patients viewed the condensed genetic counseling video with the option to receive testing the same day between 3/2015 and 8/2015. 162/295 (55%) of these patients received testing. The transition from a referral method to the video counseling method resulted in a significant increase of patients tested (p < 0.001).

Conclusion

Using a genetic counseling video and providing an immediate option for testing significantly increased the proportion of patients with ovarian, fallopian or peritoneal carcinoma who received genetic testing.

Classification of Extraovarian Implants in Patients With Ovarian Serous Borderline Tumors (LMP) Based on Clinical Outcome



abstract:
 Classification of Extraovarian Implants in Patients With Ovarian Serous Borderline Tumors (Tumors of Low Malignant Potential) Based on Clinical Outcome

 The classification of extraovarian disease into invasive and noninvasive implants predicts patient outcome in patients with high-stage ovarian serous borderline tumors (tumors of low malignant potential). However, the morphologic criteria used to classify implants vary between studies. To date, there has been no large-scale study with follow-up data comparing the prognostic significance of competing criteria. Peritoneal and/or lymph node implants from 181 patients with high-stage serous borderline tumors were evaluated independently by 3 pathologists for the following 8 morphologic features: micropapillary architecture; glandular architecture; nests of epithelial cells with surrounding retraction artifact set in densely fibrotic stroma; low-power destructive tissue invasion; single eosinophilic epithelial cells within desmoplastic stroma; mitotic activity; nuclear pleomorphism; and nucleoli. Follow-up of 156 (86%) patients ranged from 11 to 264 months (mean, 89 mo; median, 94 mo). Implants with low-power destructive invasion into underlying tissue were the best predictor of adverse patient outcome with 69% overall and 59% disease-free survival (P<0.01). In the evaluation of individual morphologic features, the low-power destructive tissue invasion criterion also had excellent reproducibility between observers ([kappa]=0.84). Extraovarian implants with micropapillary architecture or solid nests with clefts were often associated with tissue invasion but did not add significant prognostic value beyond destructive tissue invasion alone. Implants without attached normal tissue were not associated with adverse outcome and appear to be noninvasive. Because the presence of invasion in an extraovarian implant is associated with an overall survival analogous to that of low-grade serous carcinoma, the designation low-grade serous carcinoma is recommended. Even though the low-power destructive tissue invasion criterion has excellent interobserver reproducibility, it is further recommended that the presence of an invasive implant be confirmed by at least 2 pathologists (preferably at least 1 of whom is an experienced gynecologic pathologist) in order to establish the diagnosis of-low grade serous carcinoma.

Friday, July 22, 2016

Applying the Chronic Care Model to Support Ostomy Self-management



Medscape

 Findings:
A total of 118 goals were identified by 38 participants. Eighty-seven goals were physical, related to the care of the skin, placement of the pouch or bag, and management of leaks; 26 were social goals, which addressed engagement in social or recreational roles and daily activities; and 5 were psychological goals, which were related to confidence and controlling negative thinking. Although the goals of survivors of cancer with an ostomy are variable, physical goals are most common in self-management training.

Hormone Therapy: No Effect on Cognition After Menopause (in younger healthy women)



Medscape

podcast (25:06 min) Episode #14—The Latest in Genetics and Women’s Cancers



podcast

 Cancer Conversations Podcast—Episode #14—The Latest in Genetics and Women’s Cancers July 22, 2016 / by

 The Cancer Conversations series features Q&A-style conversations with Dana-Farber physicians, clinicians, and researchers. Topics include breast cancer research, precision cancer medicine, integrative therapies, cancer genetics, and more. Visit the Cancer Conversations page for more episodes and the Dana-Farber podcast page for more cancer podcast series.

We are Your Ontario Doctors Facebook (aka the politics of healthcare)



We are Your Ontario Doctors | Facebook

ABCB1 (MDR1) induction defines a common resistance mechanism in paclitaxel- and olaparib-resistant ovarian cancer cells



Abstract
 
Methods:
We created novel A2780-derived ovarian cancer cell lines resistant to paclitaxel and olaparib following continuous incremental drug selection. MTT assays were used to assess chemosensitivity to paclitaxel and olaparib in drug-sensitive and drug-resistant cells±the ABCB1 inhibitors verapamil and elacridar and cross-resistance to cisplatin, carboplatin, doxorubicin, rucaparib, veliparib and AZD2461. ABCB1 expression was assessed by qRT-PCR, copy number, western blotting and immunohistochemical analysis and ABCB1 activity assessed by the Vybrant and P-glycoprotein-Glo assays.

Conclusions:
We describe a common ABCB1-mediated mechanism of paclitaxel and olaparib resistance in ovarian cancer cells. Optimal choice of PARP inhibitor may therefore limit the progression of drug-resistant disease, while routine prescription of first-line paclitaxel may significantly limit subsequent chemotherapy options in ovarian cancer patients.

Room for improvement: An examination of advance care planning documentation among gyn oncology patients



abstract

Highlights

  • Most patients were familiar with advance directives.
  • Less than half of those surveyed had created advance directives.
  • Advance directive creation rates were impacted by patient characteristics.

Short title: role of ovarian niche in ovarian tumorigenesis



open access
Redefining the origin and evolution of ovarian cancer: A hormonal connection
 July 20, 2015 

 (pdf) Accepted Preprint first posted on 20 July 2016 as Manuscript ERC-16-0209

Abstract
Ovarian cancer has the highest mortality of all female reproductive cancers. Late diagnosis, tumor heterogeneity, and the development of chemoresistance contribute to this statistic and works against patient survival. Current studies have revealed novel concepts that impact our view on how ovarian cancer develops. The greatest impact is on our understanding that as a disease, ovarian cancer has multiple cellular origins and that these malignant precursors are mostly derived from outside of the ovaries.
In this review, we propose a new concept of a step-wise developmental process that may underwrite ovarian tumorigenesis and progression: (1) migration to/recruitment of the ovaries; (2) seeding and establishment in the ovaries; (3) induction of a dormant cancer stage; and (4) expansion and tumor progression. We will discuss the relationship of each step with the changing ovarian function and milieu during the reproductive age and subsequent occurrence of menopause. The realization that ovarian cancer development and progression occurs in distinct steps is critical for the search of adequate markers for early detection that will offer personalized strategies for prevention and therapy.

Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal Cancer Treatment (PDQ®) - July 14, 2016



Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal Cancer Treatment (PDQ®) 

 eg.:

 Treatment Option Overview

Ovarian Germ Cell Tumors Treatment (PDQ®) - July 14, 2016



Ovarian Germ Cell Tumors Treatment (PDQ®) 

eg.:

Treatment Option Overview

Long-term survival of patients with mismatch repair-deficient, high-stage ovarian clear cell carcinoma (MSH2/6)



abstract:
Long-term survival of patients with mismatch repair-deficient, high-stage ovarian clear cell carcinoma 
 21 JUL 2016

Aims

Gynaecological cancer patients with germline mutations appear to have a better prognosis than those with sporadic malignancies. Following the observation of long-term survival in a patient with stage III ovarian clear cell carcinoma (CCC) and possible Lynch syndrome (LS), DNA mismatch repair (MMR) protein immunohistochemistry was performed in a series of high-stage CCC and correlated with patient outcomes.

Methods and Results

Thirty-two consecutive cases of stage III/ IV ovarian CCCs accessioned between 1992 and 2015 were examined. The tumours from two patients (6%), including the index case, showed loss of MSH2/MSH6 expression while MLH1/PMS2 staining was retained. The index patient subsequently developed colonic and rectal carcinomas that were also MSH2/MSH6 deficient while the second patient had a genetically confirmed germline MSH2 mutation. All other tumours showed retained expression of the four MMR proteins. The two patients with MMR protein-deficient tumours were alive 160 months and 124 months following surgery whereas the median survival of patients with MMR protein-intact CCCs was 11.8 months (75th and 25th percentiles of 8.1 months and 39.3 months, respectively), with 21 patients deceased due to tumour.

Conclusions

Larger studies are required but high-stage, MMR protein-deficient CCCs may have a relatively favourable prognosis.

Thursday, July 21, 2016

What is a PARP Inhibitor? | Dana-Farber Cancer Institute | Science Illus...



Online Patient Forum - National Patient Safety Foundation (free to join)



NPSF Online Forum Survey Results - National Patient Safety Foundation
 6/18/2015
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Genomics in Clinical Practice, Part 1: The Rise of Multiplex Gene Testing for Cancer



Medscape
 July 20, 2016
 
Editor's Note:
 
This is the first in a three-part series on Medscape Oncology designed to update and familiarize practicing oncologists with the most important issues in multiplex and genomic testing.
 
In the 20 years since the first cancer gene test became available, the number and variety of tools available to clinicians for genetic analysis has exploded, far outpacing researchers' understanding of their clinical use. At the recent annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, experts discussed the rise of multiplex gene panels and what new studies show about their integration in cancer care.

Single-Gene Assays Give Way to Multiplex Testing

Types of Panels 

Table 1. Examples of Genes Included on Multiplex Gene Panels(a)

Multiplex Panels in Practice

Single-Gene vs Multiplex Testing

Table 2. Posttesting Surgical Procedures for Patients With a VUS


I think it is really important to think about an individual's preference and their tolerance for ambiguity," said Dr Isaacs. "In June 2016, there is still a reasonable chance if you send someone for multigene panel testing that you will find a mutation in a moderate penetrance gene or you will get a VUS, and you have to make sure the patient feels comfortable with that. I think the technology has outpaced our medical knowledge, but our medical knowledge will catch up."

Dr Kurian disclosed research funding from Ambry Genetics, GenDx, Genomic Health, Invitae, and Myriad Genetics. Dr Idos disclosed research funding from Myriad. Dr Isaacs disclosed honoraria from Genentech/Roche, Pfizer, Genentech, and Novartis. Dr Weitzel has disclosed no relevant financial relationships.

 

open access: Use of CA-125 Tests and Computed Tomographic Scans for Surveillance in Ovarian Cancer



open access:
Use of CA-125 Tests and Computed Tomographic Scans for Surveillance in Ovarian Cancer | JAMA Oncology
July 21, 2016 
 
Importance  A 2009 randomized clinical trial demonstrated that using cancer antigen 125 (CA-125) tests for routine surveillance in ovarian cancer increases the use of chemotherapy and decreases patients’ quality of life without improving survival, compared with clinical observation. The Society of Gynecologic Oncology guidelines categorize CA-125 testing as optional and discourage the use of radiographic imaging for routine surveillance. To date, few studies have examined the use of CA-125 tests in clinical practice.
 
Objectives  To examine the use of CA-125 tests and computed tomographic (CT) scans in clinical practice before and after the 2009 randomized clinical trial and to estimate the economic effect of surveillance testing.


Main Outcomes and Measures  The use of CA-125 tests and CT scans before and after 2009. Secondary outcomes included the time from CA-125 markers doubling to retreatment among women who experienced a rise in CA-125 markers before and after 2009, and the costs associated with surveillance testing using 2015 Medicare reimbursement rates.



Routine Cancer Antigen 125 Surveillance—The Fatal Attraction of Testing



Editorial
 

The article by Esselen et al1 in this issue of JAMA Oncology belongs to the category of health services research that asks how the introduction of new evidence influences clinical practice. In the instance they examined—publication of a study that showed routine cancer antigen 125 (CA-125) surveillance was harmful—the answer seems to be “not at all.” In the 6 NCI-designated cancer centers they studied, the use and frequency of CA-125 testing of women in remission after initial treatment for ovarian cancer was similar in the years before and after the study. In both periods, almost all such patients received CA-125 testing approximately every 3 to 4 months. This is actually quite a remarkable observation. Why did practice not change?

It is instructive to reread the original study by Rustin et al2,3 that questioned the use of CA-125 testing. It was a well-conducted multicenter randomized trial of 529 women who were in remission after initial chemotherapy for ovarian cancer. All patients received CA-125 testing every 3 months, but the treating physicians did not know the results. If and when a CA-125 test exceeded twice normal, patients were randomized into what they called early and delayed treatment groups, with randomization stratified by several prognostic factors. For patients in the early treatment group, their physicians were notified of the CA-125 results. In the delayed treatment group the results were withheld, and any decisions about further treatment were based on clinical recurrence. Most women in the early treatment group started chemotherapy soon after the notification of elevated CA-125 results. Those in the delayed treatment group started about 5 months later. Median survival was not different: 25.7 months in the early treatment group vs 27.1 months in the delayed treatment group. However, median time to deterioration in global health score or death was significantly longer in the delayed treatment group (5.8 vs 3.2 months, P =  .002). The delayed treatment group also underwent fewer cycles of chemotherapy, were less likely to receive third-line chemotherapy, and had 5 more months to live in remission after their initial treatment.2,3

The question for discussion then becomes: why was there no change in practice in response to good evidence? It is not as if physicians are incapable of rapid change in practice in the face of new information. It happens all the time when the information favors new or more treatment.4,5 For example, we assessed change in practice associated with the report showing a 2% absolute survival improvement at 18 months with taxane plus doxorubicin compared with doxorubicin alone in breast cancer patients with positive nodes. The oral report6 of these results in 1998, 5 years before the actual publication of the trial, was associated with a rapid shift to taxanes with a more than doubling in use within 3 months.5

Why did this not occur with the Rustin study? One could argue that there was no change because the clinical guidelines did not change. This is somewhat circular, because the 6 centers studied by Esselen et al1 were leading academic medical centers, populated by clinicians who also sit on the committees that write the guidelines.

I will propose 2 sets of factors contributing to the lack of an obvious change in practice in response to the Rustin study. The first relates to the fundamental attractiveness of testing, and the second involves how the Rustin study was framed by the authors and subsequent commentators.

Physicians practice in a sea of uncertainty. Making life-altering decisions based on incomplete information is 1 of the major stresses of becoming a physician. There are good and bad ways of dealing with that stress. Over confidence is 1 bad way. We all have encountered physicians who practice a “my way or the highway” style. A more acceptable means to reduce uncertainty is to seek more information through testing. The past 2 decades have witnessed a proliferation of new cancer tests and improvements in older ones. Highly sensitive scans and molecular and genetic markers allow us to more accurately characterize risk for or extent of disease and response to treatment, reducing uncertainty in decision making.
As the tests proliferated, questions arose whether more information is always a good thing. Magnetic resonance imaging for uncomplicated low back pain can lead to unnecessary surgery.7 After routine fetal monitoring was introduced, childbirth became a surgical procedure for a quarter of women.8 The dissemination of prostate-specific antigen screening was followed by an iatrogenic epidemic of prostate cancer.9,10

This is a difficult message to accept. How can more information possibly hurt? Avoiding information sounds antiscientific. Can we not still obtain the information but interpret it more wisely? A nice sentiment, but it lacks evidence of feasibility in real life. The analyses by Esselen et al1 suggest that information on increased CA-125 drove initiation of second line chemotherapy as rapidly after the report2,3 by Rustin as before.

Another difficulty involves telling physicians that they may be doing the wrong thing. Whether it involves tests or treatments, it is no easy task to convince physicians that they are causing more harm than good. There are a number of predictable responses to reports such as the 1 by Rustin et al2,3 One is what I call the moving target. “Okay, so that surgery (or radiotherapy or whatever) had bad outcomes, but you don’t understand that the techniques have improved dramatically since the time of your data.” Such a response has the advantage of sometimes being true. Other responses include questioning the patient selection: “Those aren’t the people I see in my practice” or the physicians studied: “No wonder it didn’t work. I don’t do it that way!”

All 3 of these responses and more greeted the Rustin study.11,12 What did not occur was any change in practice. Readers might want to conduct a thought experiment to ask themselves: “What if the results reported for delayed treatment were found instead for a new chemotherapy regimen? How would the report have had an effect on practice?”

The second set of reasons has to do with framing the results of the Rustin study. The 2 approaches studied by Ruskin et al2,3 were characterized as early vs delayed treatment, but that was not what they studied, at least not in my opinion. They were in essence comparing CA-125 surveillance every 3 months vs no testing. The “no testing” group received CA-125 testing, but since the results were not released to the physicians, it was the same as not testing. The findings of the study are then best framed as routine surveillance with CA-125 testing is harmful in patients diagnosed with ovarian cancer in remission after initial treatment.

Another factor that impedes clear thinking about harmful tests and treatments is the injection of medical economics into the discussion. Discussions of cost-effectiveness can make clinicians uncomfortable. The results of cost-effectiveness analyses can vary widely depending on the assumptions. And why should physicians act as societal financial gatekeepers? It is difficult enough helping patients decide on what is best for them without introducing the concept of what is best for society. In addition, such discussions can be seen by our patients as attempts at rationing their care. The suspicion that other patients, perhaps those with better insurance or better connections, might be receiving better treatment can destroy trust in the physician.
But in the context of CA-125 testing, the issue of cost-effectiveness becomes absurd. How can a test or treatment be cost-effective if it is not effective —indeed, if it is harmful? Thus, I am uncomfortable with the focus on the economic impact of continued CA-125 testing by Esselen et al.1 It is not by any means irrelevant, but it muddies the issue. Once again, the findings of the Ruskin study are that routine surveillance testing is harmful. That should be the focus for subsequent decisions by clinicians, payers, and policy makers—not the costs involved.
And, of course, the women with ovarian cancer contribute to the decisions to obtain C-125 testing. While physicians may be challenged dealing with uncertainty, many of our patients refuse absolutely to tolerate it. They want to know, even if that knowledge can lead to harm. Thus, in a shared decision making context, most patients will choose more information.13 But why would clinicians present the option of CA-125 testing? Shared decision making does not require that physicians present the patient with harmful options. We do not discuss heart transplants with patients who have mild congestive heart failure. Why would we discuss CA-125 testing with women who have ovarian cancer in remission?
Will the practice of obtaining routine CA-125 testing change? I doubt it. The moving target argument is too strong. There will be better tests, and more effective treatments. And studies like that of Rustin with uncomfortable results are usually not replicated.14 The issue is allowed to fade away. The fatal attraction of more information is too compelling.

References

Esselen  KM, Cronin  AM, Bixel  K,  et al.  Use of CA-125 tests and computed tomographic scans for surveillance in ovarian cancer [published online July 21, 2016]. JAMA Oncol. doi:10.1001/jamaoncol.2016.1842.
Rustin  GJ, Van Den Berg  ME. A randomized trial in ovarian cancer (OC) of early treatment of relapse based on CA125 level alone vs delayed treatment based on conventional clinical indicators (MRC OV05/EORTC 55955 trials). ASCO Ann Meet Proc. 2009;27(18s):1.
Rustin  GJ, van der Burg  ME, Griffin  CL,  et al; MRC OV05; EORTC 55955 investigators.  Early versus delayed treatment of relapsed ovarian cancer (MRC OV05/EORTC 55955): a randomised trial. Lancet. 2010;376(9747):1155-1163.
PubMed   |  Link to Article
Jackevicius  CA, Anderson  GM, Leiter  L, Tu  JV.  Use of the statins in patients after acute myocardial infarction: does evidence change practice? Arch Intern Med. 2001;161(2):183-188.
PubMed   |  Link to Article
Giordano  SH, Duan  Z, Kuo  YF, Hortobagyi  GN, Freeman  J, Goodwin  JS.  Impact of a scientific presentation on community treatment patterns for primary breast cancer. J Natl Cancer Inst. 2006;98(6):382-388.
PubMed   |  Link to Article
Henderson  IC, Berry  D, Demetri  GD,  et al. Improved disease-free and overall survival from the addition of sequential paclitaxel but not from the escalation of doxorubicin dose in the adjuvant chemotherapy of patients with node-positive primary breast cancer. Proc ASCO. 1998;17:101a.
Webster  BS, Cifuentes  M.  Relationship of early magnetic resonance imaging for work-related acute low back pain with disability and medical utilization outcomes. J Occup Environ Med. 2010;52(9):900-907.
PubMed   |  Link to Article
Placek  PJ, Taffel  SM, Moien  M.  Cesarean rate increases in 1985. Am J Public Health. 1987;77(2):241-242.
PubMed   |  Link to Article
Welch  HG, Albertsen  PC.  Prostate cancer diagnosis and treatment after the introduction of prostate-specific antigen screening: 1986-2005. J Natl Cancer Inst. 2009;101(19):1325-1329.
PubMed   |  Link to Article
Howrey  BT, Kuo  YF, Lin  YL, Goodwin  JS.  The impact of PSA screening on prostate cancer mortality and overdiagnosis of prostate cancer in the United States. J Gerontol A Biol Sci Med Sci. 2013;68(1):56-61.
PubMed   |  Link to Article
Morris  RT, Monk  BJ.  Ovarian cancer: relevant therapy, not timing, is paramount. Lancet. 2010;376(9747):1120-1122.
PubMed   |  Link to Article
Rustin  G, van der Burg  M, Griffin  C, Qian  W, Swart  AM.  Early versus delayed treatment of relapsed ovarian cancer. Lancet. 2011;377(9763):380-381.
PubMed   |  Link to Article
Markman  M, Petersen  J, Belland  A, Burg  K.  CA-125 monitoring in ovarian cancer: patient survey responses to the results of the MRC/EORTC CA-125 Surveillance Trial. Oncology. 2010;78(1):1-2.
PubMed   |  Link to Article
Goodwin  JS, Goodwin  JM.  The tomato effect. Rejection of highly efficacious therapies. JAMA. 1984;251(18):2387-2390.
PubMed   |  Link to Article

Safety Alerts - Oral Liquid Docusate Sodium: Recall - Contaminated with B. Cepacia



Oral Liquid Docusate Sodium

HRT: No Impact on Memory in Early Menopause



Medpage Today

 These results therefore run contrary to the "timing hypothesis" that suggests a benefit to hormone therapy if taken early in menopause as opposed to later on.
 Limitations to the study include that generalizability may be limited to healthy postmenopausal women, and that it was not designed to examine short-term effects on estradiol or effects on the risks of mild cognitive impairment or Alzheimer's disease.

Glossary of Terms - (terms and phrases used across the health care spectrum)



Glossary of Terms 
 
The glossary below is a resource for understanding terms and phrases used across the health care spectrum. From scientific definitions and emerging fields of medicine to processes and regulatory jargon, it provides simple and straightforward explanations helping you better understand America’s biopharmaceutical industry.

Hereditary cancer syndromes as model systems for chemopreventive agent development



open access


Wednesday, July 20, 2016

Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types



abstract
Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types
 
Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10−8 seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type–specific expression quantitative trait locus and enhancer–gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10−5 in the three-cancer meta-analysis. 

SIGNIFICANCE: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers.

Study explores positive aspects of physicians' attitudes towards patients



medical news

Critical care of patients with cancer - open access



open access

 Approximately 5% to 10% of patients with cancer will develop a life-threatening condition that necessitates ICU admission.[9-12]
 However, caution is needed when interpreting the results in the literature on ICU treatment for patients with cancer and when deriving conclusions for clinical practice. The vast majority of studies is retrospective and demonstrates considerable heterogeneity. It remains controversial whether the observed improvements in survival of critically ill patients with cancer are solely the result of advances in treatment of the underlying malignancy and progress in critical care.[38-40] Part of the improvements that were seen could be because of selection bias or earlier ICU admission of critically ill patients with cancer. Furthermore, there are substantial practice variations at the physician, hospital, country, and temporal levels. Thus, published data concerning cancer critical care, such as changes in ICU survival of patients with cancer, may be confounded by differences in clinical practice, case mix, and admission policies.[41]

Table 1. Causes for Intensive Care Unit Admission of Patients With Cancera
  1. ARF indicates acute respiratory failure; ATRA, all-trans retinoic acid; ICU, intensive care unit; PRES, posterior reversible encephalopathy syndrome; TRALI, transfusion-associated lung injury; TACO, transfusion-associated circulatory overload. aThe list summarizes some of the most frequent causes for ICU admission of patients with cancer.
Infections
• Pneumonia
• Sepsis
Oncologic emergencies
• Superior vena cava syndrome
• Tumor lysis syndrome
• Hypercalcemia
Noninfectious ARF
• TRALI
• TACO
• Pneumonitis
• Alveolar hemorrhage
• Engraftment syndrome
Surgery
• Regular postsurgical care
• Postsurgical complications, eg, bleeding
Adverse drug reactions
• Anaphylaxis
• Cytokine release syndrome
• ATRA syndrome
• Thrombotic microangiopathy
Neurologic complications
• Seizures
• PRES
Cardiovascular disease
• Myocardial infarction
• Congestive heart failure
• Arrhythmias
• Pulmonary thromboembolism

Conclusion

Comprehensive care for critically ill patients with cancer is a collaborative effort, and close cooperation between oncology as well as palliative and critical care is essential. Collaborative decision making is a cornerstone of high-quality critical care for patients with cancer. Like palliative medicine, critical care should be integrated early and seamlessly into the management of these patients. This will facilitate the early identification of patients who will most likely profit from aggressive management and the provision of optimal palliative care to those who are unlikely to benefit from intensive care. The ultimate goal should be to provide every critically ill patient who has cancer with high-quality critical care that is as tailored to his or her needs and personal preferences as the drugs that are used to treat their tumor.

AICR Research Conference: Nutrition, Physical Activity and Weight Management Nov 14-16



Conference
  

About the Conference:

The AICR 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.

How Can a Valid Research Agenda for Patient-Reported Outcomes Be Defined Without Patient Input? Comment/Article



Commentary (partial view)
JAMA Network
 Patient-centered outcomes research (PCOR) seeks to improve the quality of health care by ensuring that patients’ values and preferences are included in the research process. Methods to incorporate patient-reported outcomes (PROs) along with other clinical metrics are central to effective PCOR strategies.2 Crude markers of success are insufficient: patients likely care about 30-day mortality, but longer-term survival, functional outcome, and quality of life are paramount.3 As experienced researchers funded by the Patient Centered Outcomes Research Institute, we greatly appreciate the timely research agenda developed by Pezold and colleagues.4 We applaud their foresight to convene an inaugural Patient-Reported Outcomes in Surgery Conference. Although their methods were mostly sound, we question the validity of the proposed research agenda because of 1 major oversight.





Original Investigation |

Defining a Research Agenda for Patient-Reported Outcomes in Surgery Using a Delphi Survey of Stakeholders

Importance  Identifying timely and important research questions using relevant patient-reported outcomes (PROs) in surgery remains paramount in the current medical climate. The inaugural Patient-Reported Outcomes in Surgery (PROS) Conference brought together stakeholders in PROs research in surgery with the aim of creating a research agenda to help determine future directions and advance cross-disciplinary collaboration.

 Results  Of the 143 people registered for the conference, 137 provided valid email addresses. There was a wide range of attendees, with the 3 most common groups being plastic surgeons (28 [19.6%]), general surgeons (19 [13.3%]), and researchers (25 [17.5%])....

(background) Sexism in science: did Watson and Crick really steal Rosalind Franklin’s data? | Science | The Guardian



media article

 The race to uncover the structure of DNA reveals fascinating insights into how Franklin’s data was key to the double helix model, but the ‘stealing’ myth stems from Watson’s memoir and attitude rather than facts.

 Franklin died of ovarian cancer in 1958, four years before the Nobel prize was awarded to Watson, Crick and Wilkins for their work on DNA structure. She never learned the full extent to which Watson and Crick had relied on her data to make their model......

.....Our picture of how the structure of DNA was discovered, and the myth about Watson and Crick stealing Franklin’s data, is almost entirely framed by Jim Watson’s powerful and influential memoir, The Double Helix. Watson included frank descriptions of his own appalling attitude towards Franklin, whom he tended to dismiss, even down to calling her ‘Rosy’ in the pages of his book – a nickname she never used (her name was pronounced ‘Ros-lind’). The epilogue to the book, which is often overlooked in criticism of Watson’s attitude to Franklin, contains a generous and fair description by Watson of Franklin’s vital contribution and a recognition of his own failures with respect to her – including using her proper name.
It is clear that, had Franklin lived, the Nobel prize committee ought to have awarded her a Nobel prize, too – her conceptual understanding of the structure of the DNA molecule and its significance was on a par with that of Watson and Crick, while her crystallographic data were as good as, if not better, than those of Wilkins. The simple expedient would have been to award Watson and Crick the prize for Physiology or Medicine, while Franklin and Watkins received the prize for Chemistry.
Whether the committee would have been able to recognise Franklin’s contribution is another matter. As the Tim Hunt affair showed, sexist attitudes are ingrained in science, as in the rest of our culture.

DNA pioneer James Watson: The cancer moonshot is 'crap' - interview



science news (interview)

 On his involvement in current cancer research:
I’m not at war with the cancer community, but they ignore me and I ignore them.

Quantification of Somatic Chromosomal Rearrangements in Circulating Cell-Free DNA from (serous) Ovarian Cancers



open access
July 20, 2016
 

Table 1: Patients’ clinical characteristics.


 For eight out of the ten patients tested, junctions identified in DNA of the primary tumor were also detected in the cfDNA derived from pre-surgical plasma (Table 1). Of these eight, three demonstrated a continued presence of the ctDNA post-surgery, consistent with the presence of disease, which was documented at the time of the blood draw. In five patients, ctDNA could not be detected post-surgery, in accord with the lack of detectable disease observed at the time of the blood draw. Thus, for these eight cases, perfect concordance was observed between ctDNA detection and clinical presentation at the time of the blood draw. In two of the ten cases, somatic rearrangements could not be detected in the patient plasma.
  Recently, ctDNA increases in breast cancer were found to indicate recurrence earlier than rises in CTCs or CA 15-3. Furthermore, detection of ctDNA in half of these cases was possible an average of 5 months before radiologically confirmed disease progression was observed3,25. Similar results have been reported in gynecological cancer18. More work will need to be done in OC patients to study how fluctuations in ctDNA% correlate with other clinical indicators of recurrence over multiple time-points.

Liquid biopsies offer hope for earlier treatment, better tracking of ovarian cancer (Mayo)



medical news

 The study was done on 10 patients in advanced stages of ovarian cancer.
 When post-surgery DNA matched that of the tumor, patients were later found to have had a recurrence of ovarian cancer. However, when the post-surgery DNA did not match the DNA of the tumor, patients were found to be in remission.

Cerulean Receives FDA Fast Track Designation for CRLX101 for the Treatment of Platinum-Resistant Ovarian Cancer



Business Wire


CRLX101 is being evaluated in combination with weekly paclitaxel for the treatment of recurrent platinum-resistant ovarian carcinoma in a Phase 1b/2 clinical trial. Data from the Phase 1b portion of the trial were the subject of an oral presentation at the Gynecologic Oncology 2016 Conference in May. These data showed that five of the first nine patients (56%) enrolled in the trial achieved partial responses. Of note, five of the nine patients enrolled in the Phase 1b trial previously failed Avastin® (bevacizumab) and three of these five patients achieved partial responses. Cerulean is conducting this trial in collaboration with the GOG and expects to provide an update at the European Society for Medical Oncology 2016 Congress.

In 2015, CRLX101 was granted Orphan Drug designation for the treatment of ovarian cancer.

New MDL (Multidistrict Litigation) sought for cases over J&J talc powder and ovarian cancer



Reuters
July 20, 2016 


A federal judicial panel has been asked to consolidate nearly a dozen lawsuits filed in U.S. federal courts alleging Johnson & Johnson failed to warn women that using its talc-based powders for feminine hygiene could increase their risk of ovarian cancer.
The July 15 motion from plaintiffs' firm Don Barrett asks the U.S. Judicial Panel on Multidistrict Litigation to create a new multidistrict litigation for talc-powder claims before U.S. District Judge David Herndon in the Southern District of Illinois.

2012/2016: Behavioural Economics Explains Why Ontario Doctors Are So Livid :: Longwoods.com



Behavioural Economics Explains Why Ontario Doctors Are So Livid

 Essays August 2012
Behavioural Economics Explains Why Ontario Doctors Are So Livid
Ontario is in a fiscal mess and is looking to its physicians to help out. The government wants to freeze the total amount of money paid to physicians, which means rolling back the fees on a number of diagnostic and surgical procedures. Some physicians’ incomes will drop. Shockingly, they are not amused....


Monique Moreau wrote:
Posted 2016/07/19 at 11:09 AM EDT

You seem to have forgotten the 1990's in Ontario when many physicians did leave, or not even establish here, because of Rae economics, with clawbacks, individual physician caps, reduced medical school slots, and so on. It took 15 years to recover.
The excess of current physician people power flows from the cuts to availability of OR time and hospital beds. The outcome of that is people waiting ever longer for their procedures and treatment. But, yes, by all means, pile it on to the backs of physicians; we are used to being the scapegoat for the poor management of the health care dysfunctional system in Ontario.
Now let's announce to the nurses, teachers, police, firefighters, and so on that they are earning too much, more than society can afford, and they need to have their salaries rolled back 7-30%. Let's see how that plays out.

Tentative agreement between doctors and (Ontario) province 'horrifying,' doctors group says



CBC News

Expanded Access Updates (U.S.) Jul 19, 2016



JAMA Network


Recently completed efforts to streamline the “compassionate use” process physicians use to obtain investigational drugs and biologics for their patients include a shortened request form and new support documents.
Physicians can use the Individual Patient Expanded Access Investigational New Drug Application—Form FDA 3926—to request expanded access to investigational drugs when patients with serious or immediately life-threatening diseases have no comparable or satisfactory alternative therapy. It should take about 45 minutes to complete the new form, according to the FDA. Along with the new form, the agency has released step-by-step instructions on how to complete it.

Ottawa Hospital managers, after eating the food for a week, say changes are coming



Ottawa Citizen

(author: Dr. Y. Pan) Cardiovascular Toxicity of Bevacizumab in Long-term Survival of Recurrent Ovarian Cancer: A Case Report



open access - case report

Cardiovascular Toxicity of Bevacizumab in Long-term Survival of
Recurrent Ovarian Cancer: A Case Report
Yi Pan1
1 Department of Neurology, School of Medicine, Saint Louis University, St. Louis, MO, USA
Correspondence: Yi Pan, MD, Ph.D, Associate Professor, Departmetn of Neurology, School of Medicine, Saint Louis University 1438 South Grand Boulevard, St. Louis, MO 63104, USA.

Published: July 18, 2016


The present case may represent many recurrent ovarian cancer patients who have benefited greatly from emerging target therapies, such as bevacizumab, and have survived longer with an improved quality of life, but also later developed adverse effects including cardiovascular disease.
 To reap the benefits of long term bevacizumab treatment, efforts should be made to diagnose cardiovascular complications and to treat them aggressively to minimize the deleterious adverse effects of cancer therapy.



Introduction: Bevacizumab has been shown to improve progression-free survival in women with ovarian cancer in multiple clinical trials. Cardiovascular toxicity is reported in the case of a long term survivor of recurrent ovarian cancer.  

Case Report: A 47-year-old woman was diagnosed as stage IIIC, Grade 3 endometrioid adenocarcinoma of the ovary. She had been treated with 4 debulking surgeries and 6 different chemotherapy regimens for 9 years. However, remission diminished over this time period to only one month. Bevacizumab was
administrated with additional chemotherapies, and prolonged survival was demonstrated over the next 5 years, including ongoing remission of 18 months to date. New onset hypertension was developed at the 10th month of
bevacizumab treatment, and proteinuria was found at the 12th month. Patient presented symptoms of coronary artery disease during the 31th month of bevacizumab treatment, and was soon treated with 4 stents, whereby
symptoms resolved. After the 36th month of bevacizumab, the patient had non ST elevated myocardial infarction and peripheral vascular disease. Bevacizumab was terminated thereafter. In the following 18 months, the patient was treated with angioplasty 2 times for coronary artery occlusion, and with an additional stent. This was followed with coronary artery bypass graft. She also had an angioplasty for right femoral artery stenosis. Throughout most of the 14 year disease course, the patient maintained a good quality of life. As patients achieve long term survival from bevacizumab treatment, cardiovascular complications should be recognized and treated aggressively to minimize the adverse effects of cancer therapy.


1. Introduction

Bevacizumab is a vascular endothelial growth factor (VEGF) inhibitor. It has improved progression-free survival in women with ovarian cancer in both first-line chemotherapy (GOG-0218 and ICON7 trials), and second-line
chemotherapy in platinum-sensitive (OCEANS trial) and platinum-resistant (AURELIA trial) recurrent ovarian cancer (Burger et al., 2011; Perren et al., 2011; Aghajanian et al., 2012; Pujade-Lauraine et al., 2014). The Food and Drug Administration (FDA) approved bevacizumab for the treatment of patients with platinum-resistant recurrent ovarian cancer in combination with paclitaxel or one other chemotherapy regiment in 2014. The most common vascular toxicities of bevacizumab, from those clinical trials, are hypertension and proteinuria.
Coronary artery and peripheral artery diseases as vascular toxicities of bevacizumab are lacking in the literature, which may be due to limited long-term follow up…...