Ovarian Cancer and Us (blog): what you were reading this week - top 10 (+how to follow)

blog (see blog on how to follow - it can't get any easier) Note: all spam filtered and deleted before posting, no advertising, blog has no funding = totally independent

#1: Immunotherapy for Ovarian Cancer - Cancer Research...
#2: Cancer immunotherapy is moving fast. Here’s what y...
#3: The generalizability of NCI-sponsored clinical tri...
#4: Ovarian Cancer Canada - selected financials 2014-2...
#5: (popular writing) I Have Cancer and Haven't Learne...
#6: ESMO 2016 October 7-11 (link to abstract book)
#7: Body Powder and Ovarian Cancer Risk—What Is the Ro...
#8: FDA clears phase 2 trial of drug candidate for ile...
#9: (age range 7mo-14 yrs) Juvenile granulosa cell tum...
#10: HHS Whiteboard on Health Care Data - YouTube (3:13...

Patients Canada - Priorities for a new Health Accord (Patients Survey)

Patients Canada survey (survey monkey)

 

Have your voice heard by our ministers of health

In two weeks the Federal Minister of Health and each provincial health minister will be setting priorities for Canada’s health care for the years ahead. There will be no patients at these meetings to inform what those priorities should be.   
Patients Canada wants to make sure the health ministers understand what matters most to patients. Help us do this by responding to this short questionnaire so that we can communicate your preferences to the ministers!  Respondents will receive a summary of the survey results.

Opinion: Catholic hospitals have no right to refuse assisted dying (public hospital system - Ontario)

opinion - The Globe and Mail
 Daphne Gilbert is an associate professor of law, University of Ottawa

 All Ontario hospitals, Catholic and others, exist to deliver medically necessary services, and are funded by the province for that purpose.
 

Genomics of Ovarian Cancer Progression Reveals Diverse Metastatic Trajectories Including Intraepithelial Metastasis to the Fallopian Tube (note: sporadic/brca/non-serous..)

Blogger's Note: technical but worth reading and in the context of sporadic high-grade ovarian cancer; late metastasis

open access (pdf) 

while our study focused on sporadic HGSOC

Anti-tumour effects of resveratrol and pterostilbene on ovarian cancer (theses)

 Wiki:
Pterostilbene is a stilbenoid chemically related to resveratrol. In plants, it serves a defensive phytoalexin role.^[1]
                                   ~~~~~~~~~~~~~~~~~~~
open access:
Anti-tumour effects of resveratrol and pterostilbene on ovarian cancer.

 View/Open Hosking_J_MSc_2016_thesis.pdf (1.832Mb)

 
Ovarian cancer is the most lethal gynaecologic malignancy, with a high mortality rate that is associated with the difficulty of treating the disease. This is due to the typical onset of symptoms when the disease is at a fairly advanced stage. Improved treatment strategies are required to improve longevity in patients. Recently polyphenols, secondary metabolites in plants, have aroused interest with respect to the treatment of cancer. The purpose of this study was to investigate the effect of two polyphenols, resveratrol and its derivative pterostilbene, on cell metabolism and proliferation in two ovarian cancer cell lines, OVCAR-5 and SKOV-3 that were grown in a three dimensional culture. The proteins VEGF, AKT, EGFR, HER2, cyclin D2 and PCNA were investigated to identify any possible changes to signalling pathways following exposure to the polyphenols. Both resveratrol and pterostilbene affected spheroid metabolism and proliferation in a dose- and cell line-dependant manner. Vascular endothelial growth factor and expression of the various proteins were affected following treatment. This study demonstrates that resveratrol and pterostilbene are capable of down regulating the cell metabolism and inhibiting proliferation in the ovarian cancer spheroids, potentially through several different pathways.

Collections

• Science: Theses and Dissertations [2980]

Reproductive/hormonal factors in relation to survival/platinum resistance among ovarian cancer cases (HRT/endometriosis...)

abstract : 
Reproductive and hormonal factors in relation to survival and platinum resistance among ovarian cancer cases : British Journal of Cancer

Background:

Ovarian cancer survival is poor, particularly for platinum-resistant cases. The previous literature on pre-diagnostic reproductive factors and ovarian cancer survival has been mixed. Therefore, we evaluated pre-diagnostic reproductive and hormonal factors with overall survival and, additionally, platinum-chemotherapy resistance.

Methods:

We followed 1649 invasive epithelial ovarian cancer cases who were enrolled between 1992 and 2008 for overall mortality within the New England Case-Control Study and abstracted chemotherapy data on a subset (n=449). We assessed pre-diagnostic reproductive and hormonal factors during in-person interviews. We calculated hazard ratios (HRs) using Cox-proportional hazards models.

Results:

We observed 911 all-cause deaths among 1649 ovarian cancer cases. Self-reported endometriosis and longer duration of hormone therapy use were associated with improved survival (HR: 0.72; 95% confidence interval (CI): 0.54–0.94 and HR, 5 years vs never: 0.70; 95% CI: 0.55–0.90, respectively). Older age at menopause and menarche were associated with worse survival (HR, 50 vs >50 years: 1.23; 95% CI: 1.03–1.46 and HR, 13 vs <13 years: 1.24; 95% CI: 1.06–1.44, respectively). We observed no association between oral contraceptive use, parity and tubal ligation, and overall survival. No significant associations were observed for any of the reproductive and hormonal factors and platinum resistance.

Conclusions:

These results suggest that pre-diagnostic exposures such as endometriosis and HT use may influence overall survival among ovarian cancer patients.

Risk Prediction for Epithelial Ovarian Cancer in 11 United States–Based Case-Control Studies

abstract:
Risk Prediction for Epithelial Ovarian Cancer in 11 United States–Based Case-Control Studies: Incorporation of Epidemiologic Risk Factors and 17 Confirmed Genetic Loci

 Abbreviations: AUC, area under the curve; COGS, Collaborative Oncological Gene-Environment Study; EOC, epithelial ovarian cancer; GWAS, genome-wide association study; MCMC, Markov chain Monte Carlo; MHT, menopausal hormone therapy; OC, oral contraceptive; OCAC, Ovarian Cancer Association Consortium; ROC, receiver operating characteristics; SNP, single nucleotide polymorphism.

Previously developed models for predicting absolute risk of invasive epithelial ovarian cancer have included a limited number of risk factors and have had low discriminatory power (area under the receiver operating characteristic curve (AUC) < 0.60). Because of this, we developed and internally validated a relative risk prediction model that incorporates 17 established epidemiologic risk factors and 17 genome-wide significant single nucleotide polymorphisms (SNPs) using data from 11 case-control studies in the United States (5,793 cases; 9,512 controls) from the Ovarian Cancer Association Consortium (data accrued from 1992 to 2010). We developed a hierarchical logistic regression model for predicting case-control status that included imputation of missing data. ....... The best predictive power was obtained in the full model among women younger than 50 years of age (AUC = 0.714); however, the addition of SNPs increased the AUC the most for women older than 50 years of age (AUC = 0.638 vs. 0.616). Adapting this improved model to estimate absolute risk and evaluating it in prospective data sets is warranted.

(Lynch Syndrome/microsatellite instability eg. MSI-H) DNA repeat stretches tied to cancer progression and survival | UW HSNewsBeat

media

The team used a new technique to analyze sequences of all the genes from nearly 6,000 tumors from 18 different kinds of cancer. The researchers obtained the sequencing information from a massive genome database storehouse called The Cancer Genome Atlas. Their technique and the availabily of this atlas allowed them to examine more than 200,000 microsatellite sites in many different cancer types.
They found that most cancer types had examples of tumors with microsatellite instability. They also learned that different cancer types had distinct patterns of mutation across their microsatellites. Over half of the microsatellite instability sites they uncovered were within or near so-called “cancer genes” — genes that that are implicated in cancer development and progression. This finding suggests the microsatellite mutations may be causing these genes to malfunction.

 The researchers also observed a paradox: patients who had tumors with comparatively more unstable microsatellite sites tended to survive longer.

Salipante and his colleagues hypothesize that cancers cells with relatively high numbers of microsatellite instability events are producing more mutated proteins of all kinds, not just cancer genes.  These mutated proteins draw the attention of the immune system and trigger immune attacks that slow tumor progression.

Patient View 2016 survey results: The specific unmet needs/gaps in scientific information about cancer

SURVEY RESULTS
  (pdf download)

Dear  health campaigner,

You are receiving this email because you responded to a May 2016 survey from us on the

“Use of scientific information about cancer among carers, patients and the public”

[This survey was commissioned and sponsored by AstraZeneca]

We are pleased  to say that as many as 124 cancer-oriented patient/carer groups took part in the survey, and gave us their opinions on the subject.

Two of the more important findings from the survey are:

(i.) 99% of respondent patient/carer groups reported that people living with cancer (and their families/carers) want to know HOW cancer treatments work; and

(ii.) over 90% of respondent patient/carer groups stated that people living with cancer must understand scientific concepts about the disease if they are to better manage their cancer.

How breast cancer screening could be better and less painful

Science news

 The breast cancer screening tests offered to women may in many cases be unnecessarily painful. New research shows that strong compression of the breast during mammography screening does not automatically lead to a better basis for diagnosis.

Trabectedin (Yondelis) as a chemotherapy option for patients with BRCA deficiency

abstract
 

Highlights

• •We sought if BRCA deficiencies are associated with clinical responses to trabectedin.
• •BRCA genes are an important predictive indicator of sensitivity to trabectedin.
• •Improved response to trabectedin is a hallmark of BRCA1/2-mutated carriers.
• •Stratification based on BRCA mutations should become standard in upcoming trials.

Abstract

Trabectedin is a marine-derived product that was originally isolated from the Caribbean sea squirt Ecteinascidia turbinata and the first anticancer marine drug to be approved by the European Union. It is currently used as a single agent for the treatment of patients with soft tissue sarcoma after failure of anthracyclines and ifosfamide, or for those patients who are unsuited to receive these agents, and in patients with relapsed, platinum-sensitive ovarian cancer in combination with pegylated liposomal doxorubicin. Trabectedin has a unique multi-faceted mechanism of action that involves transcription regulation and DNA repair systems, including transcription-coupled nucleotide excision repair and homologous recombination repair (HRR) as the main hallmarks of its antiproliferative activity. In addition, trabectedin has shown the ability to modulate the tumor microenvironment. Indeed, the activity of trabectedin is related to altered function and expression of DNA repair genes, such as BRCA1 (BReast-CAncer susceptibility gene 1) and BRCA2. The particular sensitivity of sarcoma, ovarian and breast cancer cells deficient in HRR, previously observed in preclinical models, now has been confirmed in the clinical setting as well, suggesting that BRCA mutations are associated with improved clinical responses to trabectedin. Current efforts are focused on the evaluation of these unique features of trabectedin and on the identification of predictive factors for patients with an objective to determine whether a deficiency of HRR DNA repair pathway could impact the clinical benefit achieved from trabectedin.

The Problem With Ovarian Cancer Screening Tests (overview of recent media/screening)

Huffington Post

(blog) Nimesh P. Nagarsheth, MD
Associate Professor of Obstetrics, Gynecology, and Reproductive Science
Icahn School of Medicine at Mount Sinai
Associate Director of Gynecologic Oncology
The Mount Sinai Hospital

Universal tumor screening for Lynch syndrome: health-care providers' perspectives : Genetics in Medicine : Springer Nature

  reflex testing: automatic, routine
                  ~~~~~~~~~~~~~~~~~~~~~~~               
abstract:
Universal tumor screening for Lynch syndrome: health-care providers' perspectives

Purpose:

Population-based reflex testing of colorectal tumors can identify individuals with Lynch syndrome (LS), but there is debate regarding the type of patient discretion such a program warrants. We examined health-care providers’ views and experiences to inform the design of a reflex-testing program and their perspectives regarding an opt-out option.

Methods:

We interviewed providers managing LS or colorectal cancer patients, including surgeons, genetic counselors, oncologists, primary-care physicians, and gastroenterologists. Qualitative data were analyzed thematically using constant comparison techniques.

Results:

Providers supported a reflex-testing program because of the current lack of coordinated immunohistochemistry (IHC) testing and underascertainment of LS patients as well as the opportunity to standardize the increasing use of genomic tests in practice. Most supported an opt-out after reflex testing because they felt that IHC is akin to other pathology tests, which are not optional. Some favored an opt-out before testing because of concern for patients experiencing distress, insurance discrimination, or a diagnostic odyssey that may be inconclusive.

Conclusion:

Providers support a reflex-testing program to improve the identification and management of suspected LS patients. However, how to support meaningful information provision to enable an opt-out without jeopardizing testing uptake and the anticipated public health benefits remains a policy challenge.

Affiliations

1. Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, Ontario, Canada

2. Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada

3. Independent Qualitative Researcher, Toronto, Ontario, Canada

4. Department of Surgery, St. Michael’s Hospital, Toronto, Ontario, Canada

5. Department of Family and Community Medicine, Sinai Health System, Toronto, Ontario, Canada

6. Department of Surgery, University of Toronto, Toronto, Ontario, Canada

7. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada

8. Cancer Care Ontario, Toronto, Ontario, Canada

9. Department of Medicine, University of Toronto, Toronto, Ontario, Canada

NEJM — The Changing Face of Clinical Trials (sundry articles)

NEJM — A collection of articles that examine the current challenges in the design, performance, and interpretation of clinical trials.

Leptomeningeal metastasis from gynecologic cancers diagnosed by brain MRI

Leptomeningeal carcinomatosis (LC) is a rare complication of cancer in which the disease spreads to the membranes (meninges) surrounding the brain and spinal cord. LC occurs in approximately 5% of people with cancer and is usually terminal.
                        ~~~~~~~~~~~~~~~~~~~~~~

abstract

 Leptomeningeal metastasis (LM) is rarely observed in gynecologic cancers. As gadolinium-enhanced magnetic resonance imaging (Gd-MRI) is highly effective for diagnosing LM, the aim of this study is to describe the clinical behaviors and outcomes of LM patients who were diagnosed by Gd-MRI. After securing institutional review board approvals, we retrospectively reviewed patient records. Eight patients were found to have LM from gynecological malignancies. Primary tumors included three ovarian, one tubal, one peritoneal, two endometrial, and one cervical cancer. Gd-MRI of the brain and the spine is indicated as the high priority inspection for the diagnosis of this devastating complication.

(age range 7mo-14 yrs) Juvenile granulosa cell tumor of the ovary: a clinicopathologic study

abstract

Study Objective

To report on the clinical characteristics and outcome of pediatric patients with juvenile granulosa cell tumor (JGCT) of the ovary.

Design, Setting, and Participants

Patients with histopathologically confirmed ovarian JGCT diagnosed between 1990 and 2016 were identified. Data on the clinical presentation, surgical management, oncologic management, laboratory investigation, follow-up, and outcome were collected. Tumor was staged according to the International Federation of Gynecology and Obstetrics (FIGO) criteria.

Results

Eight patients were diagnosed with ovarian JGCT during the study period. The median age at presentation was 3 years (range 0.7 – 14 years). Precocious puberty was the presenting symptom in all five prepubertal children; abdominal distension due to mass effect was the presenting symptom in three children greater than 9 years of age. In patients who had preoperative serologic testing, estradiol (n=3) and inhibin (n=3) were elevated. Five patients had stage I disease, and three had stage III. All stage I patients underwent salpingo-oophorectomy as the only treatment. Stage III patients received adjuvant chemotherapy. After a median follow-up of 6.2 years, six patients (75%) were alive without evidence of disease. One stage I patient with germline p53 mutation and PTEN mutation, died due to subsequent liposarcoma. One patient with stage IIIB disease developed recurrence detected by elevated inhibin serum level, and died due to progressive disease despite receiving multiple chemotherapy regimens.

Conclusion

JGCT has a favorable prognosis in patients with stage I disease following surgical resection alone. Adjuvant chemotherapy may be indicated in patients with higher stage tumors.

Key Words

• Juvenile granulosa cell tumor;
• pathology;
• inhibin B;
• chemotherapy

FDA clears phase 2 trial of drug candidate for ileus, adhesions

pharma press release
 

Postoperative Ileus and Surgical Adhesions: Phase 2 Study
Location: Multinational

Multi-center study of 100-120 patients, evaluating pre- and post-treatment of LB1148 administered orally for major abdominal surgeries. Enrollment expected to begin in August 2016. For ileus, the study will measure the number of hours from surgical closure to resolution of postoperative ileus via various returning gastrointestinal functions. Length of stay will also be measured. For adhesions, study will evaluate whether LB1148 reduces the number of surgical adhesions formed in certain types of abdominal surgeries where a 2^nd operation is required.

clincialtrials.gov:

A Study to Evaluate LB1148 for Return of Gastrointestinal Function and Adhesions in Subjects Undergoing Bowel Resection (PROFILE)

This study is not yet open for participant recruitment. (see Contacts and Locations)

Verified August 2016 by Leading BioSciences, Inc

Sponsor:

Leading BioSciences, Inc

Information provided by (Responsible Party):

Leading BioSciences, Inc

ClinicalTrials.gov Identifier:

NCT02836470

First received: July 13, 2016

Last updated: August 29, 2016

Last verified: August 2016

History of Changes

 

Criteria

Inclusion Criteria:

• Scheduled to undergo an elective (non-emergent) bowel resection with or without a planned stoma via laparotomy or minimally invasive technique. This includes any subject in which a resection of the small intestine, colon, or rectum is performed for any elected indication.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02836470

Contacts

Contact: Thomas M Hallam, PhD	858.704.4900	tom.hallam@leadingbiosciences.com

(plagiarism) Retraction notice to 'Does ovarian stimulation for IVF increase gynaecological cancer risk? A systematic review and meta-analysis'

Retraction notice to 'Does ovarian stimulation for IVF increase gynaecological cancer risk? A systematic review and meta-analysis'

Reprod Biomed Online. 2016 Oct;33(4):534. doi: 10.1016/j.rbmo.2016.08.001.

Retraction notice to 'Does ovarian stimulation for IVF increase gynaecological cancer risk? A systematic review and meta-analysis' [Reproductive BioMedicine Online 31 (2015) 20-29].

Zhao J¹, Li Y¹, Zhang Q¹, Wang Y¹.

Author information

Abstract

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. The authors have plagiarized part of a paper that had already appeared in Hum. Reprod. Update, Volume 19 (2013) 105-123http://dx.doi.org/10.1093/humupd/dms051. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.

open access: Prevalence and distribution pattern of nodal metastases in advanced ovarian cancer

Blogger's Note: previously posted as abstract only

open access