Sunday, November 27, 2016

(see blog for comments) UGT1A1 polymorphism as a prognostic indicator of stage I ovarian clear cell carcinoma patients treated with irinotecan

Blogger's Note (comments-mine): 1) Japan has a much higher rate of clear cell ovarian cancer than Western countries and, as well, presents more often in early stages; 2) trials on CPT-11 (Irinotecan) started a couple of decades ago and seemed in the Japanese trial patients to confer a survival advantage; 3) published longterm data results (2016) were negative; 4) full text of this article is subscriber-based but this abstract may be a sub-analysis (hard to tell from abstract) and references are not attached to the abstract
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UGT1A1 polymorphism as a prognostic indicator of stage I ovarian clear cell carcinoma patients treated with irinotecan

We investigated whether UGT1A1 polymorphisms are associated with the prognosis of ovarian cancer patients treated with irinotecan. UGT1A1 genotypes were analyzed in 11 stage I ovarian clear cell carcinoma patients who received irinotecan as first-line therapy. Progression-free survival, overall survival and adverse events were also assessed for each genotype. Three patients harbored UGT1A1*1/*6 while another three harbored UGT1A1*1/*28. Two patients with a wild-type genotype experienced recurrence and one died, whereas no recurrence or death was observed in patients with heterozygous genotypes. Adverse events tended to be more severe in patients with UGT1A1*6 and *28, although progression-free survival and overall survival rates tended to be better than in wild-type; the differences were not significant. We conclude that UGT1A1 polymorphisms have the potential to be a prognostic marker of irinotecan treatment.
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Wiki:
Pharmacogenetics
Genetic variations within the UGT1A1 gene have also been associated with the development of certain drug toxicities. The UGT1A1*28 variant, the same allele behind many cases of Gilbert syndrome, has been associated with an increased risk for neutropenia in patients receiving the chemotherapeutic drug irinotecan,^[15]^[16] and the U.S. Food and Drug Administration recommends on the irinotecan drug label that patients with the *28/*28 genotype receive a lower starting dose of the drug.^[17] The *28 allele has also shown associations with an increased risk for developing diarrhea in patients receiving irinotecan.^[15]^[16] The UGT1A1*6 variant, more common in Asian populations than the *28 variant, has also shown associations with the development of irinotecan toxicities. Patients who are heterozygous or homozygous for the *6 allele may have a higher risk for developing neutropenia and diarrhea as compared to those with the UGT1A1*1/*1 genotype.^[15]^[16]

Saturday, November 26, 2016

Mutational heterogeneity in non-serous ovarian cancers (PTEN)

Abstract B11: Mutational heterogeneity in non-serous ovarian cancers. | Clinical Cancer Research

PTEN stood out as a gene containing truncating mutations in many samples.

OA: Genetic basis of Cowden syndrome and its implications for clinical practice and risk management (+PTEN/OC)

Genetic basis of Cowden syndrome and its implications for clinical practice and risk management

. 2016; 9: 83–92.

Published online 2016 Jul 13. doi: 10.2147/TACG.S41947

PMCID: PMC4948690

Huntsman Cancer Institute Family Cancer Assessment Clinic Salt Lake City, UT, USA

Ambry Genetics Medical Affairs Aliso Viejo, CA USA

Correspondence: Amanda Gammon, Room 1148 2000 Circle of Hope Dr, Huntsman Cancer Institute, Family Cancer Assessment Clinic, Salt Lake City, UT 84112, USA

Two cases of ovarian tumors (one dysgerminoma and one cystadenoma) have been reported in women with CS.30 Unlike the much more common hereditary breast and ovarian cancer syndrome, the risk of ovarian cancer does not appear to be significantly elevated in CS.

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
PTEN in Ovarian Cancer
(MyGeneCounsel -
National Cancer Institute-designated Comprehensive Cancer Center in Tennessee)

Table 1. Frequency of Somatic Gene Mutations in Epithelial Ovarian Cancer (EOC).

	EOC Overall	Type I				Type II
Gene Mutation		Low Grade Serous	Clear Cell	Endometrioid	Mucinous	High Grade Serous
PTEN	20% (Kurman and Shih 2011)	<1% mutation (TCGA 2011)	20% (Landen, Birrer, and Sood 2008)	<1–5% (Kuo et al. 2009; Willner et al. 2007)	20–31% (Kurman and Shih 2011; Willner et al. 2007)	Rare

(eg. Cowden Syndrome/ovarian cancer) Genetics of Breast and Gynecologic Cancers (PDQ®)—Health Professional Version - National Cancer Institute

Genetics of Breast and Gynecologic Cancers (PDQ®)—Health Professional Version - National Cancer Institute (updated Nov 22, 2016)

Associated Genes and Syndromes

Breast and ovarian cancer are present in several autosomal dominant cancer syndromes, although they are most strongly associated with highly penetrant germline pathogenic variants in BRCA1 and BRCA2. Other genes, such as PALB2, TP53 (associated with Li-Fraumeni syndrome), PTEN (associated with Cowden syndrome), CDH1 (associated with diffuse gastric and lobular breast cancer syndrome), and STK11 (associated with Peutz-Jeghers syndrome), confer a risk to either or both of these cancers with relatively high penetrance.....

Ontario’s doctors’ fight for patient privacy pays off - OMA press release

Ontario’s doctors’ fight for patient privacy pays off

press release

Toronto, ON Nov. 25, 2016 – For months, doctors have been challenging the provincial government on its flawed legislation to redesign primary care – Bill 41. The legislation proposes sweeping changes to the way care is delivered and the ability of government investigators to have access to patient’s private and confidential health records, without warrant or consent.
Following the appearance of Dr. Stephen Chris, President Elect of the Ontario Medical Association (OMA) at a public hearing on Bill 41, the government indicated that it is planning to bring forward a number of changes to protect patient privacy next week in committee.
“The Minister of Health appears to have recognized that patient privacy must never be compromised, and has indicated a willingness to take the necessary steps to protect it,” said Dr. Virginia Walley, President of the OMA. “It is unfortunate that patient privacy was left so vulnerable under Bill 41- if physicians were consulted and listened to, government could have gotten this right the first time.”
There are still aspects of Bill 41 that remain deeply concerning to doctors. Bill 41, as written, will allow government to dictate the kind of care doctors should provide to patients. The legislation increases the amount of red-tape and paper work for doctors, taking precious time away from providing direct patient care. Additional bureaucracy is a prominent feature of Bill 41, with the creation of 80 Sub-LHINs that will siphon health-care dollars away from the tests and treatments patients need.
“The Ontario government has been quick to reassure the public that doctors were consulted on Bill 41, but it is clear from the changes being implemented at such a late stage that we did not have very important and crucial conversations.” said Dr. Walley. “More than 80 per cent of Ontarians trust doctors to make decisions about their health-care system, which is not surprising when our current government is busy writing laws that put their interests ahead of those of patients.”
The OMA’s submission and proposed amendments to Bill 41 are available upon request.

For more information, please contact:
Danielle Milley, Senior Advisor Media Relations
Office: 416-599-2580 or 1-800-268-7215 ext. 3008
Mobile: 647-300-0081
Email: danielle.milley@oma.org

Nadia Daniell-Colarossi, Manager Media Relations
Office: 416-340-2970 or 1-800-268-7215 ext. 2970
Mobile: 416-804-4600
Email: nadia.daniell-colarossi@oma.org

The disparate origins of ovarian cancers: pathogenesis and prevention strategies : Nature Reviews Cancer : Nature Research

abstract
The disparate origins of ovarian cancers: pathogenesis and prevention strategies : Nature Reviews Cancer : Nature Research
Published online 25 November 2016
Ovarian cancer is the fifth cause of cancer-related death in women and comprises a histologically and genetically broad range of tumours, including those of epithelial, sex cord-stromal and germ cell origin. Recent evidence indicates that high-grade serous ovarian carcinoma, clear cell carcinoma and endometrioid carcinoma primarily arise from tissues that are not normally present in the ovary. These histogenetic pathways are informing risk-reduction strategies for the prevention of ovarian and ovary-associated cancers and have highlighted the importance of the seemingly unique ovarian microenvironment.

OA: Orthodox Jewish Thought Leaders’ Insights Regarding BRCA Mutations: A Descriptive Study

Journal of Oncology Practice

Maimonides Medical Center, Brooklyn, NY

Ovarian Cancer Dilemma

Therefore, when a report appears entitled “Refusal of Recommended Chemotherapy for Ovarian Cancer”¹, a malignancy where chemotherapy is long known to be associated with a high objective response rate and relatively rapid and clinically meaningful palliation of symptoms (eg, abdominal pain and bloating, decreased appetite, fatigue), it is reasonable to inquire what exactly is being reported and what lessons might be learned to impact such refusal?

The specific study in question examined patients in the National Cancer Data Base who were diagnosed with ovarian cancer (n = 147,713) over a 14-year period (January 1998 to December 2011).¹ In this database, a total of 2707 patients were reported to have “refused chemotherapy.” This conclusion was apparently drawn from a response in the database which was based on documentation in the medical records that “chemotherapy was not administered. It was recommended by the patient’s physician, but this treatment was refused by the patient, a patient’s family member, or the patient’s guardian.”¹ - See more at: http://www.onclive.com/publications/oncology-live/2016/vol-17-no-16/what-is-a-patient-who-refuses-chemotherapy-really-saying#sthash.ZkikKSE4.dpuf

Ovarian Cancer Dilemma

Friday, November 25, 2016

What Is a Patient Who Refuses Chemotherapy Really Saying? (re: ovarian cancer/refusal of chemo)

What Is a Patient Who Refuses Chemotherapy Really Saying?

“Refusal of Recommended Chemotherapy for Ovarian Cancer” - See more at: http://www.onclive.com/publications/oncology-live/2016/vol-17-no-16/what-is-a-patient-who-refuses-chemotherapy-really-saying#sthash.ZkikKSE4.dpuf

Ovarian Cancer Dilemma

Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update

open access
Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics : Genetics in Medicine
17 November 2016

....The intent of the original incidental findings recommendations¹ was that clinical diagnostic laboratories performing exome or genome sequencing should report known pathogenic (KP) or expected pathogenic (EP) variants in the 56 American College of Medical Genetics and Genomics (ACMG) genes even when unrelated to the primary medical reason for testing. Subsequently, the ACMG revised the terminology to “secondary findings” (SFs) because these genes are intentionally being analyzed, as opposed to genetic variants found incidentally or accidentally; the shift in terminology also maintained consistency with a recommendation by the Presidential Commission on Bioethical Issues.² An additional modification to the original policy included offering an option to opt-out of receiving SFs for individuals undergoing clinical genomic sequencing (GS).³ This revision was due, in part, to results from a survey of ACMG members in which more than 80% of respondents supported an option for patients undergoing GS to decline SF analysis following appropriate counseling. In addition, more than 90% of respondents supported a minimum list of SFs that would be updated and refined over time. This article concluded that according to its membership, the ACMG “should update a list of genes to be assessed when clinical genome-scale sequencing is performed. Informed consent is necessary, and reporting of secondary findings should be optional.”^4.....

Fraser Institute's wait time survey: Does it still count if most doctors ignored it? - Health - CBC News

CBC News
Nov 25, 2016

Only around 20% of doctors responded to questionnaire.

Fill out this survey and have a chance to win $2,000 — that's the annual enticement from the Fraser Institute, an offer made to thousands of doctors whose names appeared on a mailing list.
But it wasn't tempting enough to get doctors to participate.
No medical oncologists in Saskatchewan, Manitoba or New Brunswick took the bait.
Zero responses came back from radiation oncologists in New Brunswick or from cardiovascular surgeons in Manitoba.
Not a single plastic surgeon in Prince Edward Island or Newfoundland answered the questionnaire.
Across Canada, just seven per cent of psychiatrists on the list bothered to answer the short survey asking them to estimate how long their patients are waiting for care.
The Fraser Institute is a think-tank that has long advocated for more private-sector options within the Canadian health care system.....

Why most clinical research is not useful - John Ioannidis

Cancerworld

It makes no sense to perform clinical research that has no relevance to patient care, so why do we do it, and how can we stop? John Ioannidis ponders the problem and offers some suggestions.

This article first appeared in PLoS Medicine
(doi:10.1371/journal.pmed.1002049), on 21 June 2016,
and is republished here under a creative commons license.
Illustrations are added by Cancer World

Data show only weak or modest correlations between the amount of research done and the burden of various diseases (5,6). Moreover, disease mongering affects multiple medical specialties (4,7,8).

Useful clinical research procures a clinically relevant information gain (9): it adds to what we already know. This means that, first, we need to be aware of what we already know so that new information can be placed in context (10).

Research inferences should be applicable to real-life circumstances.

Chemotherapy-Induced Peripheral Neuropathy: A Challenge for Clinicians

Cancer Network

Tricky gene mutations detected by free, fast, easy-to-use new software - UK research

Medical News
November 25, 2016

Adapted Media Release

Published: Today

Scientists have developed an easy-to-use software tool that can detect important genetic mutations that previously needed to be identified by a separate test.
The software, called DECoN, accurately and quickly detects changes in copy number of blocks of DNA called exons, by analysing sequencing data already generated to identify smaller gene changes.
It was developed by researchers at The Institute of Cancer Research, London, and the Wellcome Trust Centre for Human Genetics, Oxford.
Most gene mutations are small DNA changes within an exon. These small changes are readily detected by DNA sequencing tests.
But sometimes whole exons are deleted or duplicated. These are called exon copy number variants (exon CNVs), and they are not easily picked up by standard DNA sequencing tests.
It is vital to be able to find these variants because they are an important cause of disease. For example, about 10 percent of the BRCA1 mutations that predispose women to breast and ovarian cancer are exon CNVs. In clinical testing laboratories a separate test has traditionally been used to detect exon CNVs, but this adds considerable time and cost, and is not available for all genes. Using DECoN (which stands for Detection of Exon Copy Number variants), the researchers took advantage of the high density of sequencing data available in new gene panels to accurately detect deletions or duplications of exons. DECoN does this automatically, adding only 30 minutes to the data analysis of up to 96 samples, and without costing any more.
The team performed extensive evaluations of DECoN including in more than 1,900 clinical BRCA tests where it successfully detected all the exon CNVs.....

Professor Rahman added: "It's very important to us that our work can be as impactful as possible. We have made an easy-to-use version of DECoN freely available from www.icr.ac.uk/DECoN and the source code is also available."

video3:04 min Dr Loprinzi/Mayo: Overview of neuropathy treatment options

Oncologytube
Posted on : 10/28/16

Description: Charles Loprinzi, MD of Mayo Clinic, Rochester, MN discusses neuropathy treatment options. ASCO guidelines recommend duloxetine, an antidepressant medication, which helps but does not completely eliminate the neuropathic pain. A scrambler therapy, developed for patients with chronic pain, is another option. This therapy may reduce the neuropathic pain by up to 50%, as suggested by a study conducted by dr Thomas Smith. Scrambler therapy is an electrocutaneous treatment used daily for ten days, with a potential to eliminate neuropathic pain in patients for weeks, months, or even years. Dr Loprinzi mentions, however, that the treatment does not work in all patients, and booster treatments may be required.
Recorded at the Multinational Association of Supportive Care in Cancer (MASCC) and International Society of Ocular Oncology (ISOO) 2016 Annual Meeting on Supportive Care in Cancer held in Adelaide, Australia.

Ovarian Cancer Workup: Approach Considerations, Screening, Tumor Markers

Ovarian Cancer Workup: Approach Considerations, Screening, Tumor Markers
Updated: Aug 24, 2016

Approach Considerations
The presence of advanced ovarian cancer is often suspected on clinical grounds but can be confirmed only pathologically by removal of the ovaries or, when disease is advanced, by sampling tissue or ascitic fluid.
Current guidelines from the Society of Gynecologic Oncology and the American Society of Clinical Oncology recommend that the primary clinical evaluation for ovarian cancer include a computed tomography (CT) scan of the abdomen and pelvis with oral and intravenous contrast, and chest imaging (CT preferred) to evaluate the extent of disease and the feasibility of surgical resection.^[34]National Comprehensive Cancer Network guidelines recommend chest x-ray or CT, as clinically indicated, and ultrasound and/or abdominal/pelvic CT or magnetic resonance imaging (MRI), as clinically indicated. Positron emission tomography (PET)/CT scan or MRI may be indicated for indeterminate lesions, if the results will alter management.^[35]
MRI can increase the specificity of imaging evaluation in cases where the ultrasound appearance of the lesion is indeterminate.^[6]MRI is not definitive, however. On MRI, endometriotic cysts with enhanced mural nodules are a hallmark of ovarian cancer, but they may also be a feature of benign neoplasms and even inflammatory diseases. Large contrast-enhanced nodules on large endometriotic cysts in an elderly patient are more likely to indicate malignancy.^[36]
When imaging studies demonstrate an adnexal mass, the decision whether to observe the patient with repeat imaging or to proceed to surgical evaluation must take into account not only the imaging characteristics but also the patient's medical history, physical examination results, and cancer antigen 125 (CA125) level.^[37]Tumor markers such as CA125 are not good discriminators of benign lesions from malignant lesions in premenopausal women but have better accuracy in postmenopausal women.

Review: A radical musical A Pacifist’s Guide to the War on Cancer - The Lancet

A radical musical - The Lancet

A Pacifist’s Guide to the War on Cancer was commissioned by Complicite, the theatre company that is world renowned for trailblazing work. But this collaboration between writers Bryony Kimmings and Brian Lobel and composer Tom Parkinson succeeds on traditional grounds too. At heart, it is an exploration of a group of people with cancer. The energetic and diverse cast alternate between playing patients and relatives, and the doctors and nurses who treat them.