Tuesday, June 28, 2016

Perspective Clinical Efficacy of Ovarian Cancer Screening (country comparisons/CA125...)

open access
June 25, 2016

Conclusion
In summary, annual screening with the use of
CA125/TVS can detect the precursors of type I
ovarian carcinoma, such as cystic tumors, and identify
patients who should be closely observed. Thus annual
screening may be useful for detecting type I ovarian
carcinoma at an earlier stage. Furthermore, annual
screening may improve the prognoses or induce the
down staging (from stage IV to stage III) of cases of
type II ovarian carcinoma, which would further
increase its efficacy in Asia, and also make it effective
in Europe and the USA, just as the UKCTOCS showed
a significant mortality reduction in the UK.

chart:
(click on link above to view additional countries/details)

“It's not if I get cancer, it's when I get cancer”: Previvors' (Un)Certain health experiences regarding hereditary breast and ovarian cancer risk

abstract:
“It's not if I get cancer, it's when I get cancer”: Previvors' (Un)Certain health experiences regarding hereditary breast and ovarian cancer risk
June 23, 2016

Highlights

•: A BReast CAncer (BRCA) genetic mutation increases a patient's cancer risk.
•: Interviews were conducted with patients to understand their health experiences.
•: BRCA-positive patients experience sources of medical and familial uncertainty.
•: BRCA-positive patients experience (un)certainty as an ongoing process.
•: This research extends conceptual understandings of uncertainty in health.

Abstract

Rationale

Women with a harmful mutation in the BReast CAncer (BRCA) gene are at significantly increased risk of developing hereditary breast and ovarian cancer (HBOC) during their lifetime, compared to those without. Such patients—with a genetic predisposition to develop cancer but who have not yet been diagnosed with cancer—live in a constant state of uncertainty and wonder not if they might get cancer but when.

Objective

Framed by uncertainty management theory, the purpose of this study was to explore BRCA-positive patients' health experiences after testing positive for the BRCA genetic mutation, specifically identifying their sources of uncertainty.

Methods

Thirty-four, qualitative interviews were conducted with female patients. Participants responded to online research postings on the non-profit organization Facing Our Risk of Cancer Empowered's (FORCE) message board and social media pages as well as HBOC-specific Facebook groups. The interview data were coded using the constant comparison method.

Results

Two major themes representing BRCA-positive patients' sources of uncertainty regarding their genetic predisposition and health experiences emerged from the data. Medical uncertainty included the following three subthemes: the unknown future, medical appointments, and personal cancer scares. Familial uncertainty encompassed the subthemes traumatic family cancer memories and motherhood.

Conclusions

Overall, the study supports and extends existing research on uncertainty—revealing uncertainty is inherent in BRCA-positive patients' health experiences—and offers new insight regarding uncertainty management and HBOC risk.

(Note) This manuscript is a part of research I conducted for my dissertation at Texas A&M University. My dissertation advisor, listed on the IRB Approval Letter, was Dr. Richard L. Street Jr.

Monday, June 27, 2016

(Canada) Rights group (B.C.) to launch legal challenge of assisted-dying law

The Globe and Mail
June 27, 2016

...The rights group (B.C.) argues that the law, which passed in Parliament 10 days ago, is unconstitutional.....

(Canada) Bill S-201 Genetic Non-Discrimination Act

Bill S-201

Canadian senator wins award for work on genetic discrimination

The Globe and Mail
Monday, Jun. 27, 2016

A Canadian senator is the co-winner of this year’s second annual advocacy award from the American Society of Human Genetics.

Senator James Cowan has been cited along with the Canadian Coalition for Genetic Fairness for their roles in pushing a law that would prevent genetic discrimination in Canada.

Cowan was the sponsor for new legislation that would bar employers and insurance companies from demanding genetic testing – or asking to see genetic test results.

The fear of losing a job or insurance coverage has been repeatedly cited by Canadians who could potentially benefit from genetic screening but decline to be tested due to the ramifications.

The bill passed unanimously in the Senate in April and will be debated in the House of Commons this fall.

It would alter the Canadian Human Rights Act to include genetic discrimination, and it has penalties of up to five years in prison or up to a $1-million fine for those who abuse the law........

Sunday, June 26, 2016

Recurrent Sertoli–Leydig cell tumor of ovary in 8-year-old girl

abstract
(Case Report - Turkey)

Sertoli–Leydig cell tumors are rare sex cord-stromal neoplasms that account for <0.2% of ovarian tumors. These tumors with a retiform pattern pose difficult diagnostic problems, with the majority of being misinterpreted as serous papillary cystadenocarcinoma and endodermal sinus tumor. We report an 8-year-old female patient presented to our institution with a huge mass and pain in the lower abdomen and recurrence in the 10th months following the first operation. Only four cases of Sertoli–Leydig cell tumors have been reported under age of the eight years in the literature so far. It is difficult to define the stage and the morphology of Sertoli–Leydig cell tumors with retiform pattern in children and chemotherapy or radiotherapy administration is controversial. However, fertility sparing surgeries should be considered as a first treatment choice on the time of the diagnosis and the recurrence.

Adenocarcinoma ex-goblet cell carcinoid (appendiceal-type crypt cell adenocarcinoma) is a morphologically distinct entity with highly aggressive behavior and frequent association with peritoneal|intra-abdominal dissemination

Abstract:
Adenocarcinoma ex-goblet cell carcinoid (appendiceal-type crypt cell adenocarcinoma) is a morphologically distinct entity with highly aggressive behavior and frequent association with peritoneal|[sol]|intra-abdominal dissemination: an analysis of 77 cases : Modern Pathology
24 June 2016

High-grade versions of appendiceal goblet cell carcinoids (‘adenocarcinoma ex-goblet cell carcinoids’) are poorly characterized. We herein document 77 examples. Tumors occurred predominantly in females (74%), mean age 55 years (29–84), most with disseminated abdominal (77% peritoneal, 58% gynecologic tract involvement) and stage IV (65%) disease. Many presented to gynecologic oncologists, and nine had a working diagnosis of ovarian carcinoma. Metastases to liver (n=3) and lung (n=1) were uncommon and none arose in adenomatous lesions. Tumors had various histologic patterns, in variable combinations, most of which were fairly specific, making them recognizable as appendiceal in origin, even at metastatic sites: I: Ordinary goblet cell carcinoid/crypt pattern (rounded, non-luminal acini with well-oriented goblet cells), in variable amounts in all cases. II: Poorly cohesive goblet cell pattern (diffusely infiltrative cords/single files of signet ring-like/goblet cells). III: Poorly cohesive non-mucinous cell (diffuse-infiltrative growth of non-mucinous cells). IV: Microglandular (rosette-like glandular) pattern without goblet cells. V: Mixed ‘other’ carcinoma foci (including ordinary intestinal/mucinous). VI: goblet cell carcinoid pattern with high-grade morphology (marked nuclear atypia). VII: Solid sheet-like pattern punctuated by goblet cells/microglandular units. Ordinary nested/trabecular (‘carcinoid pattern’) was very uncommon. In total, 33(52%) died of disease, with median overall survival 38 months and 5-year survival 32%. On multivariate analysis perineural invasion and younger age (<55) were independently associated with worse outcome while lymph-vascular invasion, stage, and nodal status trended toward, but failed to reach, statistical significance. Worse behavior in younger patients combined with female predilection and ovarian-affinity raise the possibility of hormone-assisted tumor progression. In conclusion, ‘adenocarcinoma ex-goblet cell carcinoid’ is an appendix-specific, high-grade malignant neoplasm with distinctive morphology that is recognizable at metastatic sites and recapitulates crypt cells (appendiceal crypt cell adenocarcinoma). Unlike intestinal-type adenocarcinoma, it occurs predominantly in women, is disguised as gynecologic malignancy, and spreads along peritoneal surfaces with only rare hematogenous metastasis. It appears to be significantly more aggressive than appendiceal mucinous neoplasms.

Diabetes Management in Cancer Patients

Cancer Network

Clinical Vignette #1

Corticosteroid-induced hyperglycemia

Who is at risk for corticosteroid-induced hyperglycemia?

Treating and preventing corticosteroid-induced hyperglycemia

Clinical Vignette #2

PI3K-induced hyperglycemia

Who is at risk for PI3K-induced hyperglycemia?

Treating and preventing PI3K-induced hyperglycemia

References

1. Tamez-Pérez HE, Quintanilla-Flores DL, Rodríguez-Gutiérrez R, et al. Steroid hyperglycemia: Prevalence, early detection and therapeutic recommendations: A narrative review. World J Diabetes. 2015;6:1073-81.
2. McCoubrie R, Jeffrey D, Paton C, Dawes L. Managing diabetes mellitus in patients with advanced cancer: a case note audit and guidelines. Eur J Cancer Care (Engl). 2005;14:244-8.

Saturday, June 25, 2016

Why Does Cancer Risk Increase As We Get Older? (sometimes)

Insight

PLOS Medicine: Why Most Clinical Research Is Not Useful (John P. A. Ioannidis)

PLOS Medicine (open access)

June 21, 2016

Conclusion

Overall, not only are most research findings false, but, furthermore, most of the true findings are not useful. Medical interventions should and can result in huge human benefit. It makes no sense to perform clinical research without ensuring clinical utility. Reform and improvement are overdue.

Summary Points

Blue-sky research cannot be easily judged on the basis of practical impact, but clinical research is different and should be useful. It should make a difference for health and disease outcomes or should be undertaken with that as a realistic prospect.
Many of the features that make clinical research useful can be identified, including those relating to problem base, context placement, information gain, pragmatism, patient centeredness, value for money, feasibility, and transparency.
Many studies, even in the major general medical journals, do not satisfy these features, and very few studies satisfy most or all of them. Most clinical research therefore fails to be useful not because of its findings but because of its design.
The forces driving the production and dissemination of nonuseful clinical research are largely identifiable and modifiable.
Reform is needed. Altering our approach could easily produce more clinical research that is useful, at the same or even at a massively reduced cost.

Table 1. Features to consider in appraising whether clinical research is useful.

http://dx.doi.org/10.1371/journal.pmed.1002049.t001

Features of Clinically Useful Research:

Problem Base

Context Placement and Information Gain

Pragmatism

Patient Centeredness

Value for Money

Feasibility

Transparency (Trust)

Other Considerations:

Uncertainty

Other sources of evidence besides trials

Focusing on major journals

Overall Picture

YouTube: A Data Sharing Platform to Promote Precision Oncology: The Genomic Data Commons

YouTube

https://pbs.twimg.com/media/ClmOYKkWkAQKgyJ.jpg

The Eve Appeal - In memory of Louise Wisson

National Ovarian Cancer Coalition (new website)

National Ovarian Cancer Coalition

Americans Spend $30 Billion a Year Out-of-Pocket on Complementary Health Approaches

NCCIH

How much did Americans spend on different types of complementary approaches? The survey showed that:

Americans spent $14.7 billion out-of-pocket on visits to complementary practitioners. This is almost 30 percent of what they spent out-of-pocket on services by conventional physicians ($49.6 billion). They spent more on visits to complementary practitioners than on natural product supplements or self-care purchases (see below), and their mean annual out-of-pocket expenditure for practitioner visits was $433.
Americans spent $12.8 billion out-of-pocket on natural product supplements, which was about one-quarter (24 percent) of what they spent out-of-pocket on prescription drugs ($54.1 billion). The mean annual out-of-pocket expenditure in this category was about $368.
Total spending on purchases related to self-care approaches (for example, homeopathic medicines and self-help materials, such as books or CDs, related to complementary health topics) was $2.7 billion, and the mean annual out-of-pocket expenditure per user was $257.

They're going to CRISPR people. What could go wrong?

blog
June 23, 2016

By Sharon Begley

June 23, 2016

Now that a federal biosafety and bioethics committee has approved what would be the first use of the trailblazing genome-editing technology CRISPR-Cas9 in people, the obvious question arises: Could anything go wrong?

The purpose of such a Phase 1 clinical trial is to assess safety, so problems wouldn’t come as a total shock. The fact that the trial in cancer patients (which still needs OKs from the Food and Drug Administration, among others) would be funded by the new cancer institute founded this year by tech mogul Sean Parker adds a wild card. Four potential snafus:....

Confounded by Serrated Polyps? Pathologists Are, Too

Gastroenterology & Endoscopy News

Ovarian cancer screening: UKCTOCS trial – Authors' reply + References

open access: Ovarian cancer screening: UKCTOCS trial – Authors' reply - The Lancet

Ovarian cancer screening: UKCTOCS trial – Authors' reply (June 2016)

Ian J Jacobs

Mahesh Parmar

Steven J Skates

Usha Menon

Article Info

We are grateful for the positive comments about the conduct of UKCTOCS.¹ The total cost was roughly £27 million for 2·19 million woman-years of screening or follow-up, which is a remarkably low cost of about £12·30 per woman-year.

A mortality reduction of around 20% or more would be an important advance in a disease with such a poor outcome and limited progress in effective therapy. Contrary to the comment by Jim Thornton and Susan Bewley, we were clear that the “mortality reduction was not significant in the primary analysis”. Nevertheless, all of our analyses provide encouraging, but not definitive, evidence of a mortality benefit (figure). Four additional years of follow-up will provide clarity one way or the other. Although the primary outcome will continue to be ovarian or tubal cancer, the change in definition of primary peritoneal cancer by WHO in 2014 will ensure that most cases currently classified as primary peritoneal cancer will be reclassified as ovarian or fallopian tube cancer.

Figure

Summary of mortality analysis
Significant at the critical value adjusted for multiple comparisons against a control (Dunnett's correction; α=0·0258).

View Large Image | View Hi-Res Image | Download PowerPoint Slide

The analysis that excluded prevalent cases was a prespecified secondary analysis and not “data-driven” as suggested by Thornton and Bewley. We do not believe that a bias between the no screening and multimodal (MMS) groups explains these findings as was suggested by Peter Sassieni and colleagues. We do not follow their explanation for a bias, but note that matching patients from the no screening group to MMS patients on CA125 at baseline and diagnosis and years on study showed no average difference between MMS and no screening group change-points, which suggests no bias in advanced cancers at randomisation. The weighted log-rank analysis was included precisely because it was the primary statistical method used in the Prostate, Lung, Colorectal and Ovarian (PLCO) trial,² although we acknowledge the limitations of a post-hoc analysis. Using a weighted log-rank test with weights increasing with time or Royston-Parmar non-proportional hazards model was important because a late mortality benefit was observed in keeping with several other large randomised trials of cancer screening (eg, 7 years in the European Randomised Study of Screening for Prostate Cancer [ERSPC] trial,³ 9 years in the Norwegian Colorectal Cancer Prevention [NORCCAP] trial⁴). This delayed effect, which means that hazards cannot be proportional,⁵ is at least in part due to the delay in healthy participants developing cancer and dying from the disease after randomisation.

The suggestion by Paul Hoskins and Walter Gotlieb that ultrasound screening (USS) was as effective as MMS is incorrect. There was a significant stage shift in invasive epithelial ovarian or tubal and peritoneal cancer in the MMS group compared with the no screening group (stage I or II 36·1% vs 23·9%, p=0·00013), but not in the USS group (24·0% vs 23·9%, p=0·57). We have considered the possibility that one of the screening strategies could reduce mortality through prevention rather than early detection. We have no evidence to support this at present as the incidence of invasive epithelial ovarian, tubal, or peritoneal cancer was not significantly reduced in the screening groups, although there was an intriguing trend of lower incidence in the USS group, which might become clearer on longer follow-up. We are doing numerous additional analyses, which include investigating stage and morphology in the different groups over time as proposed by Hoskins and Gotlieb.

There was no industry sponsored funding or involvement in the design, conduct, or analysis of the UKCTOCS trial. Our declared interests as investigators arose through standard knowledge transfer activity developed through our employing institutions. The ROCA test, which is owned by Queen Mary University of London and Massachusetts General Hospital, pre-dates the trial and no commercial exploitation or sales occurred during the trial.

The UKCTOCS trial was funded by the Medical Research Council (G9901012 and G0801228), Cancer Research UK (C1479/A2884), and the Department of Health, with additional support from The Eve Appeal. Researchers at University College London were supported by the National Institute for Health Research, University College London Hospital, and Biomedical Research Centre. SJS received additional research support from the National Cancer Institute Early Detection Research Network (CA152990). IJJ reports personal fees from and stock ownership in Abcodia as the non-executive director and consultant; personal fees from Women's Health Specialists as the director; has a patent for the Risk of Ovarian Cancer algorithm and an institutional licence to Abcodia with royalty agreement; is a trustee (2012–14) and Emeritus Trustee (2015 to present) for The Eve Appeal; and has received grants from the Medical Research Council (MRC) UK, Cancer Research UK, the National Institute for Health Research, and The Eve Appeal. SJS reports personal fees from the LUNGevity Foundation and SISCAPA Assay Technologies as a member of their Scientific Advisory Boards; consultant fees from Abcodia; has grants from the US National Cancer Institute; and his institution Massachusetts General Hospital has licensed software to Abcodia. UM has stock ownership in and research funding from Abcodia; has received grants from the MRC, Cancer Research UK, the National Institute for Health Research, and The Eve Appeal. MP declares no competing interests.

References

Jacobs, IJ, Menon, U, Ryan, A et al. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet. 2016; 387: 945–956
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Buys, SS, Partridge, E, Black, A et al. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening randomized controlled trial. JAMA. 2011; 305: 2295–2303
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Schröder, FH, Hugosson, J, Roobol, MJ et al. Prostate-cancer mortality at 11 years of follow-up. N Engl J Med. 2012; 366: 981–990
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Holme, O, Loberg, M, Kalager, M et al. Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: a randomized clinical trial. JAMA. 2014; 312: 606–615
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The challenge of fertility preservation in cancer patients: a special focus issue from Future Oncology

Blogger's Note: not necessarily open access to all articles

open access (Editorial)

special focus issue from Future Oncology, Future Oncology, Future Medicine:

Special Focus Issue: Oncofertility – Foreword

The challenge of fertility preservation in cancer patients: a special focus issue from Future Oncology Michaël Grynberg

Editorial

Endocrine prevention of chemotherapy-induced ovarian failure Zeev Blumenfeld

Fertility preservation in cancer patients with a poor prognosis: the controversy of posthumous reproduction Janella Hudson, Susan T Vadaparampil, Christina Tamargo, and Gwendolyn P Quinn

The importance of actively involving partners in oncofertility discussions Hoda Badr

Oncofertility in gynecologic oncology: an oxymoron? Dana Marie Roque and Alessandro D Santin

Commentary

Combating radiation therapy-induced damage to the ovarian environment Francesca E Duncan, Bruce F Kimler, and Shawn M Briley

State-of-the art advances in fertility preservation for the male cancer patient Dana Livne-Segev, Ellen C Forbes, and Kirk C Lo

Fertility preservation option in young women with ovarian cancer So-Youn Kim and Jung Ryeol Lee

Research Article

Doxorubicin and cisplatin induce apoptosis in ovarian stromal cells obtained from cryopreserved human ovarian tissue Raffaella Fabbri, Maria Macciocca, Rossella Vicenti, Roberto Paradisi, Francesca Gioia Klinger, Gianandrea Pasquinelli, Enzo Spisni, Renato Seracchioli, and Alessio Papi

History of ABVD alters the number of oocytes vitrified after in vitro maturation in fertility preservation candidates Charlotte Sonigo, Alice Seroka, Isabelle Cédrin-Durnerin, Nathalie Sermondade, Christophe Sifer, and Michael Grynberg

Review

The effects of cancer therapy on women's fertility: what do we know now? Barbara Lawrenz, Nalini Mahajan, and Human Mousavi Fatemi

Freezing oocytes or embryos after controlled ovarian hyperstimulation in cancer patients: the state of the art Julie Bénard, Solène Duros, Hady El Hachem, Charlotte Sonigo, Christophe Sifer, and Michaël Grynberg

Progression-free and overall survival in ovarian cancer patients treated with CVac.......

Progression-free and overall survival in ovarian cancer patients treated with CVac, a mucin 1 dendritic cell therapy in a randomized phase 2 trial | Journal for ImmunoTherapy of Cancer | Full Text

Published: 21 June 2016

Abstract

Background

CAN-003 was a randomized, open-label, Phase 2 trial evaluating the safety, efficacy and immune outcomes of CVac, a mucin 1 targeted-dendritic cell (DC) treatment as a maintenance therapy to patients with epithelial ovarian cancer (EOC).