OVARIAN CANCER and US

Friday, June 12, 2015

Bilateral Salpingo-oophorectomy and Pelvic Organ Prolapse

Medscape

Objective. This study aims to estimate the effects of bilateral salpingo-oophorectomy (BSO) at the time of hysterectomy and estrogen therapy on vaginal prolapse.

Evaluation of Wellness Determinants and Interventions by Citizen Scientists

JAMA Network

Most medical research focuses on disease rather than health. Yet people are interested predominantly in health and wellness. Wellness refers to diverse and interconnected dimensions of physical, mental, and social well-being that extend beyond the traditional definition of health. It includes choices and activities aimed at achieving physical vitality, mental alacrity, social satisfaction, a sense of accomplishment, and personal fulfillment. Equally healthy people may differ vastly in terms of their wellness, eg, whether their life is filled with creativity, altruism, friendship, and physical and intellectual achievement. Disease is incompatible with health, but not with wellness.....

.....For too long, the research enterprise has not adequately reflected the preferences and values of people, widening the gap between the interests of researchers and study participants. Encouraging motivated people participating in high-quality cohorts to contribute to the design and conduct of simple trials could align the interests of investigators and citizen scientists interested in wellness.

Patient-Reported Outcomes in Cancer Drug Development/US Regulatory Review

JAMA Oncology

Patient-Reported Outcomes in Cancer Drug Development and US Regulatory ReviewPerspectives From Industry, the Food and Drug

Data reported directly by patients about how they feel and function are rarely included in oncology drug labeling in the United States, in contrast to Europe and to nononcology labeling in the United States, where this practice is more common. Multiple barriers exist, including challenges unique to oncology trials, and industry’s concerns regarding cost, logistical complexities.....

Multigene Panel Testing in Oncology Practice: How Should We Respond?

JAMA Oncology

A great success of modern human genetics is the identification of specific genes that, when altered, confer clinically recognized traits, such as cancer susceptibility, and enable predictive genetic testing. In past decades, cost and turn-around time limited cancer genetic risk assessment, and it was rarely feasible to test a patient for more than 1 well-defined condition (eg, hereditary breast ovarian cancer [HBOC] or Lynch syndrome)......

Using Somatic Mutations to Guide Treatment Decisions: Context Matters

JAMA Oncology

Addressing the Financial Burden of Cancer Treatment: From Copay to Can’t Pay

JAMA Oncology open access

Thursday, June 11, 2015

Safety evaluation of olaparib for treating ovarian cancer

abstract

Expert opinion: Oral olaparib 400 mg twice daily has acceptable tolerability when administered as maintenance monochemotherapy in women with relapsed OC. The common toxicities – nausea/vomiting, fatigue and anemia – are mild or moderate in severity and appear consistent across subgroups (BRCA carriers/wild-type). Though the risk is low, long-term monitoring of patients is warranted to determine the potential risk for hematological complications such as anemia, myelodysplastic syndrome or acute myeloid leukemia.

Advanced High-Grade Serous Ovarian Cancer: Frequency/Timing of Thoracic Metastases and the Implications for Chest Imaging Follow-up

abstract

Purpose

To study the frequency, timing, and associations of thoracic metastases in advanced (stage III and IV) high-grade serous ovarian cancer (HGSC) to help optimize the use of cross-sectional chest imaging.

Materials and Methods

This institutional review board–approved retrospective study with waived informed consent included 186 consecutive patients with pathologically proven advanced HGSC after primary cytoreduction (mean age ± standard deviation, 60 years ± 9.7) who underwent imaging at our tertiary cancer institution from January 2012 to December 2012 with at least 1 year of follow-up, unless there was thoracic metastasis or death. Electronic medical records and all available imaging studies were reviewed to record patient and tumor characteristics, frequency and timing of abdominal and thoracic metastases, and visibility of the first thoracoabdominal metastasis on abdominal images. Patient and tumor characteristics associated with thoracic metastases were studied by using univariate and multivariate Cox proportional analysis.

Results

After median follow-up of 57 months (interquartile range [IQR], 38–93), 175 patients (94%) developed metastatic disease; each had abdominal disease, and 76 (41%) had thoracic metastases. The first thoracoabdominal metastasis was visible on abdominal images in all 175 patients. The thoracic metastasis–free interval was longer than the abdominal disease–free interval (median, 85 months [IQR, 28–131] vs 14 months [IQR, 7–27], respectively; P < .0001). Presence of disease on abdominal images (hazard ratio, 2.56; 95% confidence interval: 1.35, 4.76) was the only factor independently associated with thoracic metastases.

Conclusion

Thoracic metastases in advanced HGSC rarely occur before abdominal disease, and first thoracoabdominal metastases are invariably visible on abdominal images. Therefore, cross-sectional chest imaging may be deferred until development of abdominal disease, with minimal risk of missing thoracic metastases.

Advances in the study of Lynch syndrome in China

open access text version

World J Gastroenterol 21(22):6861-6871. Published online 2015 June 14. doi: 10.3748/wjg.v21.i22.6861.

(Toronto) Zane Cohen Centre - 6th Lynch Syndrome Education Night

slide presentations (+ 3 pdf's)

The slides and video presentations from the 6^th Biennial Lynch Syndrome education evening for 2015 have been made available on the Zane Cohen Centre website. Click here for more information: http://zanecohencentre.com/gi-cancers/fgicr/news-and-events/ls-evening-2015

Introduction to Lynch Syndrome Evening 2015
The latest research in Lynch syndrome
Urinary tract cancer – symptoms, screening and treatment
Understanding Insurance and Genetic Testing

Monday, June 08, 2015

Clinical Trials, Disparities, and Financial Burden: It’s Time to Intervene

the Oncologist

Editor's Note: See the related articles on pages 572 and 674.

Do I Qualify? | Prevent Ovarian Cancer - free - apply online - Ontario, Canada

Do I Qualify?

You may qualify to participate in the Prevent Ovarian Cancer Program if you meet all the following criteria:

Are an Ontario resident
Are a female at least 18 years of age
Have a deceased first-degree relative (mother, sister or daughter) previously diagnosed with ovarian cancer

You will not qualify if:

You do not meet all 3 criteria listed above
Someone in your family was previously tested and identified as having a BRCA1 or BRCA2 mutation
You were previously tested and identified as having a BRCA1 or BRCA2 mutation yourself

If you think that you qualify based on these criteria, click What is the Process? to learn more.
Click Get Started to create your POCP username.

The Prevent Ovarian Cancer Program (POCP) is an initiative that aims to identify women at high risk for ovarian cancer and offer them the opportunity to reduce that risk.

Up to 20% of ovarian cancers are passed down through family members. This means that women with a family history of ovarian cancer may be at increased risk of developing the disease themselves. If we know that a woman is at high risk for developing ovarian cancer, there are steps she can take to prevent the cancer from developing in the first place. Our mission is to find these women by testing for gene changes (also known as mutations) that may otherwise not be discovered under current Ontario Ministry of Health genetic testing guidelines.

You can participate in the POCP from home. This means you will not have to come to the Princess Margret Cancer Centre in Toronto to be part of this program. If you need additional support or information during the program, we will connect you to resources in your community.

Through this program, genetic counselling and genetic testing will be available to 500 women living in Ontario who have a first-degree relative (mother, sister, daughter) with a confirmed diagnosis of a specific type of ovarian cancer called high-grade serous ovarian cancer (or “HGSC” for short), but that do not currently qualify for genetic testing through the Ontario Ministry of Health.

Participation in this program is a multi-step process that is outlined in Do I Qualify? and What is the Process? Your participation will help determine if you have an increased risk for ovarian cancer, and if so, provide you with options for reducing that risk. This life saving information may prevent you, or someone you love, from developing ovarian cancer in the future.

Sunday, June 07, 2015

Long-term mortality among women with epithelial ovarian cancer

Blogger's Note: abstract lacks critical detail, pay-per-view for full access

abstract

Highlights

•: The probability of dying from ovarian cancer decreases with time.
•: Ovarian cancer remains the most common cause of death for 15 years after diagnosis in women with stage III–IV tumors.
•: For stage I tumors, ovarian cancer remains the most common cause of death for 6 years after diagnosis.

Objectives

Patients with solid tumors are at greatest risk for dying from their cancers in the five years following diagnosis. For most malignancies, deaths from other chronic diseases begin to exceed those from cancer at some point. As little is known about the causes of death among long-term survivors of ovarian cancer, we examined causes of death by years from diagnosis.

Methods

The Surveillance, Epidemiology, and End Results (SEER) database was used to identify women diagnosed with ovarian cancer between 1988 and 2012. We compared causes of death by stage, age, and interval time after diagnosis.

Results

A total of 67,385 women were identified.

For stage I neoplasms, 13.6% died from ovarian cancer, 4.2% from cardiovascular disease, 3.6% from other causes and 2.6% from other tumors; ovarian cancer was the leading cause of death until 7 years after diagnosis after which time deaths are more frequently due to other causes.

For those with stage III–IV tumors, 67.8% died from ovarian cancer, 2.8% from other causes, 2.3% from cardiovascular disease and 1.9% from other cancers; ovarian cancer was the most frequent cause of death in years 1–15 after which time deaths were more commonly due to other causes.

Conclusions

The probability of dying from ovarian cancer decreases with time. Ovarian cancer remains the most common cause of death for 15 years after diagnosis in women with stage III–IV tumors.

Effect of Food on the Pharmacokinetics of Olaparib after Oral Dosing of the Capsule Formulation (BRCA)

abstract

BACKGROUND:

The oral, potent poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib, is well tolerated at doses of ≤400 mg twice daily (BID) (administered as capsules), and has shown efficacy in patients with advanced BRCA-mutated ovarian and breast cancer.

METHODS:

This Phase I, open-label, randomized trial investigates the effect of food on the pharmacokinetics of olaparib in patients with refractory/resistant advanced solid tumors. In Part A, a three-period crossover study, patients received a single oral dose of olaparib 400 mg (8 × 50 mg capsules) in three prandial states: fasted, a high-fat meal or a standard meal (with a 5-14 day washout). Blood samples for pharmacokinetic (PK) assessments were taken pre-dose and up to 72 h post-dose. After completing Part A, patients could enter Part B, where they would receive olaparib 400 mg BID.

RESULTS:

32 patients were randomized; 31 contributed to the PK statistical analysis and entered Part B. The presence of food slowed the rate of absorption (time to maximal plasma concentration [t _max] was delayed by ~2 h). Maximum plasma concentration (C _max) was increased by 10% following a standard meal and was unchanged with a high-fat meal (ratio of geometric means [90% confidence interval (CI)]: 1.10 [1.02-1.20] for standard and 1.00 [0.92-1.09] for high-fat meal). The extent of olaparib absorption (AUC) was increased by ~20% in the fed state (ratio of geometric means: 1.21 [1.10-1.33] for standard and 1.19 [1.08-1.31] for high-fat meal).

CONCLUSIONS:

The presence of food decreased the rate and increased the extent of absorption of olaparib following oral dosing of the capsule formulation. However, the effects of food on olaparib PK were not deemed clinically important, according to predefined criteria. Safety data were consistent with the known safety profile of olaparib.

FUNDING:

AstraZeneca.

5 yr mortality predictors in 498 103 UK Biobank participants + interactive risk calculator

The Lancet

Women (n=271 029)
Age (years) 56·75
Breast cancer, lung cancer and ovarian cancer

Interpretation
Measures that can simply be obtained by questionnaires and without physical examination were the strongest predictors of all-cause mortality in the UK Biobank population. The prediction score we have developed accurately predicts 5 year all-cause mortality and can be used by individuals to improve health awareness, and by health professionals and organisations to identify high-risk individuals and guide public policy.

Interactive Risk Calculator

This is the UbbLE Risk Calculator

You will be asked to answer 11-13 questions about your background, lifestyle and health. The questions in the risk calculator use the same wording as the original UK Biobank questions.
Based on your answers, the calculator will display your five-year risk of dying from any cause and the ‘Ubble age’ that corresponds to that risk.
The data that you enter in the questionnaire is not used by us in any way. Please read our Privacy policy for more details.

Saturday, June 06, 2015

Vaccination: Special populations are not all the same

Cleveland Clinic Journal of Medicine

Postmenopausal Meigs' Syndrome in Elevated CA-125

abstract - case report

Meigs' syndrome is a benign ovarian tumor associated with ascites and pleural effusion. Elevated cancer antigen 125 (CA-125) in Meigs' syndrome is an unusual clinical condition reported in few cases. We report here on a 61-year-old woman who presented with dyspnea; in imaging assessment, a heterogeneous pelvic mass measuring 12 × 11 cm with ascitic fluid was reported. Pleural effusion was detected on Chest X-ray. Aspiration of pleural fluid showed no evidence of malignancy. CA-125 level was 347 IU/mL. The patient underwent laparotomy during which a mass measuring 12 × 11 cm was detected in her left adnexa. Histology showed ovarian thecoma. The mass was resected, and, after that, the symptoms disappeared and CA-125 level reached 19 IU/mL. The patient had experienced no problem after 12 months of follow up. Although postmenopausal women with ovarian tumor, ascites, pleural effusion, and elevation of CA-125 levels probably have malignant ovarian tumors, Meigs' syndrome must be considered in the differential diagnosis.

Ovarian cancer mortality and industrial pollution (Spain)

abstract

Highlights

•: We studied excess mortality due to ovarian cancer near Spanish industries.
•: Integrated nested Laplace approximations were used as a Bayesian inference tool.
•: We found excess ovarian cancer mortality near all industrial groups as a whole.
•: Risk also was found in towns near industries releasing carcinogens and metals.
•: Risk was associated with plants releasing polycyclic aromatic chemicals and POPs.

Abstract

We investigated whether there might be excess ovarian cancer mortality among women residing near Spanish industries, according to different categories of industrial groups and toxic substances. An ecologic study was designed to examine ovarian cancer mortality at a municipal level (period 1997–2006). Population exposure to pollution was estimated by means of distance from town to facility. Using Poisson regression models, we assessed the relative risk of dying from ovarian cancer in zones around installations, and analyzed the effect of industrial groups and pollutant substances. Excess ovarian cancer mortality was detected in the vicinity of all sectors combined, and, principally, near refineries, fertilizers plants, glass production, paper production, food/beverage sector, waste treatment plants, pharmaceutical industry and ceramic. Insofar as substances were concerned, statistically significant associations were observed for installations releasing metals and polycyclic aromatic chemicals. These results support that residing near industries could be a risk factor for ovarian cancer mortality.

BRCA Mutations Increase Fertility in Families at Hereditary Breast/Ovarian Cancer Risk

PLOS ONE: open access

Method

This hypothesis was tested within 2,150 HBOC families encompassing 96,325 individuals. Parameters included counts of breast/ovarian cancer, age at diagnosis, male breast cancer and other cancer locations. As expected, well-known clinical parameters discriminated between BRCA-mutated families and others: young age at breast cancer, ovarian cancer, pancreatic cancer and male breast cancer. The major fertility differences concerned men in BRCA-mutated families: they had lower first and mean age at paternity, and fewer remained childless. For women in BRCA families, the miscarriage rate was lower. In a logistic regression including clinical factors, the different miscarriage rate and men's mean age at paternity remained significant.

PD-1/PD-L1 Inhibitors Safe, Effective in Advanced Ovarian Cancer

PD-1/PD-L1 Inhibitors - Onclive/Asco

Friday, June 05, 2015

Small Bowel Cancer: Scoping Out a Rarity (+genetics eg Lynch Syndrome)

medscape

Medscape: What predisposing factors are associated with an increased risk for small bowel adenocarcinoma?

Michael J. Overman, MD: There are three big factors. The first is hereditary nonpolyposis colorectal cancer (HNPCC), or Lynch syndrome, which predisposes not only to colorectal cancer but also to a number of other cancers, including small bowel adenocarcinoma.....

Dr Overman: Screening poses several issues, given the rarity of the cancer and the challenges of imaging the small bowel. At present there are no cancer guidelines that recommend screening for small bowel adenocarcinoma. The screening modality would likely be a capsule endoscopy or enteroscopy, but these are invasive procedures for such a rare disease. For the general population, we don't have a screening test that is appropriate. For people with increased risk—the three categories I mentioned—we don't have good data, again because of the rarity of the disease. There are some data supporting screening in patients with Lynch syndrome, utilizing capsule endoscopy,^[3] but screening this population is not recommended in current guidelines. The frequency of screening is also uncertain.

Breaking the Bonds between “Palliative Care” and “Hospice” | ASCO Connection

Word Associations

Genome Canada | New genomics research projects to create economic and social benefits for Canadians

Genome Canada press release

TORONTO, June 5, 2015 /CNW/ - Thousands of Canadian cancer patients may soon benefit from more targeted, personalized cancer treatment following an investment by the Government of Canada.
The Honourable Ed Holder, Minister of State (Science and Technology) and Bernard Trottier, Member of Parliament for Etobicoke Lakeshore, accompanied by Lorne Hepworth, Chair of Genome Canada, announced nearly $16 million in funding for four new research projects under the third round of Genome Canada's Genomic Applications Partnership Program (GAPP)......

LifeLabs Genetics – Whole Exome Sequencing (Ontario)

Whole Exome Sequencing

Introduction

In collaboration with Centogene, LifeLabs now offers whole exome sequencing (WES). This sequencing technology looks at all the coding regions of a person’s genome, examining thousands of genes simultaneously. For this reason, WES is one of the best methods of detecting the causal mutation in complex genetic conditions, as well as identifying new mutations.
The test requires a sample from the patient as well as samples from each of the biological parents, whenever possible. Having parental samples can provide genetic insights and improve the results for the patient. There is no additional charge for the examination of the parents’ samples, however reports will not be issued for the parents.

How to order

Complete the requisition form
- Requisition link
Apply for funding from the Ministry of Health (if applicable)
- Ontario MOHLTC Application Form
Collect and send sample to LifeLabs Genetics OR have the sample collected at a Patient Service Centre
- Send samples directly to: 100 International Blvd., Toronto, ON, M9W 6J6 (1 844 363 4357)
- Find your nearest Patient Service Centre for sample collection

Incidental Findings

LifeLabs and Centogene adhere to the “ACMG Recommendations for Reporting of Incidental Findings” and will not report on findings not directly related to the cause of a disease and not listed in the ACMG guidelines. However, it does mean that we will report variants detected in certain genes that are outlined in these recommendations as being medically actionable. If you would prefer not to receive this information in your report, it is possible to opt out of this service.

Resources

Sample report click here.
View brochure

Cutaneous Clues to Diagnosing Metastatic Cancer (numerous malignancies)

medscape (slide presentation)

The knowledge system underpinning healthcare is not fit for purpose and must change (systematic reviews)

BMJ including comments

Pathobiology of ovarian carcinomas

open access

Ovarian tumors comprise a heterogeneous group of lesions, displaying distinct tumor pathology and oncogenic potentiel. These tumors are subdivided into three main categories: epithelial, germ cell, and sex-cord stromal tumors. We report herein the newly described molecular abnormalities in epithelial ovarian cancers (carcinomas). Immunohistochemistry and molecular testing help pathologists to decipher the significant heterogeneity of this disease. Our better understanding of the molecular basis of ovarian carcinomas represents the first step in the development of targeted therapies in the near future.....