Veliparib for the treatment of ovarian cancer

abstract


Introduction: Ovarian cancer represents the sixth most commonly diagnosed cancer among women, with an incidence of 6.1 cases per 100.000 women and a cumulative lifetime risk of 0.5%. Treatment is based on debulking surgery and platinum-based chemotherapy, with the potential combination with taxane. However, the recently available data on the genetic basis and aetiology of ovarian cancer has led to the development of new anticancer drugs. Poly(ADP-ribose) polymerase (PARP) inhibitors are one of the most promising new classes of targeted agents currently under investigation for the treatment of ovarian cancer. Veliparib is a small molecule that inhibits both PARP-1 and PARP-2 and was originally shown to be efficacious in BRCA-associated tumors.
Areas covered: This manuscript reviews the Phase I and II studies investigating the use of veliparib in ovarian cancer. This article also provides and discusses the pharmacokinetics and pharmacodynamics of veliparib.

Expert opinion: It is still being discussed whether PARP inhibitors should be used in a front-line or relapsed setting, alone or in combination with cytotoxic chemotherapy or as maintenance treatment. In terms of veliparib, further investigations are needed to explore its full potential in ovarian cancer. It is hoped that the ongoing phase 3 trials will help to further elucidate it potential as a treatment option.

Do critical care units play a role in the management of gynaecological oncology patients? The contribution of gynaecologic oncologist in running critical care units

Do critical care units play a role in the management of gynaecological oncology patients? The contribution of gynaecologic oncologist in running critical care units

Abstract:
 Routine post-operative care in high dependency unit (HDU), surgical intensive care unit (SICU) and intensive care unit (ICU) after high-risk gynaecological oncology surgical procedures may allow for greater recognition and correct management of post-operative complications, thereby reducing long-term morbidity and mortality. On the other hand, unnecessary admissions to these units lead to increased morbidity – nosocomial infections, increased length of hospital stay and higher hospital costs. Gynaecological oncology surgeons continue to look after their patient in the HDU/SICU and have the final role in decision-making on day-to-day basis, making it important to be well versed in critical care management and ensure the best care for their patients. Post-operative monitoring and the presence of comorbid illnesses are the most common reasons for admission to the HDU/SICU. Elderly and malnutritioned patients, as well as, bowel resection, blood loss or greater fluid resuscitation during the surgery have prolonged HDU/SICU stay. Patients with ovarian cancer have a worse survival outcome than the patients with other types of gynaecological cancer. Dependency care is a part of surgical management and it should be incorporated formally into gynaecologic oncology training programme

Impact of Chemotherapy Beyond the Third Line in Patients With Recurrent Epithelial Ovarian Cancer

abstract
 

OBJECTIVES:

The goal of this study was to determine the benefit in terms of time disease control (TDC) achieved by the succession of chemotherapy beyond the third line in patients treated for recurrent epithelial ovarian cancer. Secondary objectives were to identify patients who benefited from treatments beyond 3 lines and to estimate overall survival and disease-free progression lengths.

CONCLUSIONS: These results may justify the administration of chemotherapy beyond the third line, in particular when the 2 previous lines are effective and resulted in disease control longer than 6 months.

OCRF & Ovarian Cancer National Alliance are uniting to become Ovarian Cancer Research Fund Alliance. We’re now one strong, inspiring voice!

Ovarian Cancer 

 

Join us for a Q&A with OCRFA’s leadership on February 1st at 2pm ET. OCRFA’s CEO Audra Moran and Executive Vice President Calaneet Balas will talk more about what this exciting merger means for the ovarian cancer community, and will take questions.

Register Here

Ovarian Cancer Research Fund

14 Pennsylvania Plaza
Suite 1710
New York, NY 10122

Telephone: (212) 268-1002
Fax: (212) 947-5652
Email: info@ocrf.org

Ovarian Cancer National Alliance

1101 14th Street NW
Suite 850
Washington, DC 20005

Telephone: (202) 331-1332
Toll Free: (866) 399-6262
Fax: (202) 331-2292
Email: ocna@ovariancancer.org

NCI-Molecular Analysis for Therapy Choice (NCI-MATCH) Trial - NCI

 National Cancer Institute

 The required interim analysis is well underway and a number of changes are being made to the trial at this time. We have determined that the pause on new patient enrollments needs to remain in place until all of these activities are complete. Therefore, the enrollment pause, originally expected to lift in January 2016, has been moved to April or May 2016.

Outcome of genetic evaluation of patients with kidney cancer referred for suspected hereditary cancer syndromes

abstract

Highlights

• •
  We identified several factors that may predict positive test results in patients with kidney cancer undergoing evaluation in a clinical genetics clinic. Although these risk factors have previously been associated with cancer syndromes, a need for studies of testing practices remains.
• •
  Our data suggest that in patients with kidney cancer evaluated for hereditary cancer syndromes, young age is associated with diagnosis of RCC syndromes, whereas syndromic manifestations and multiple primaries are found in Lynch syndrome.
• •
  These results, along with clinical pathway, suggested for evaluating patients with kidney cancer for inherited cancer syndrome may be useful for practicing urologists to select patients with kidney cancer to refer for genetic counseling.

ESO, CNIO and NRCO Conference on Familial Cancer

Event

 ESO, CNIO and NRCO Conference on Familial Cancer 19/05/2016 - 20/05/2016, Madrid, Spain

  MAIN TOPICS
• Breast and ovarian cancer
• Colon and prostate cancer
• Rare cancers
• Implications of applying next generation sequencing to the diagnosis

Nonhormonal Management of Menopause-associated Vasomotor Symptoms

Medscape
 Nonhormonal Management of Menopause-associated Vasomotor Symptoms: 2015 Position Statement of The North American Menopause Society

Hematuria as a Marker of Occult Urinary Tract Cancer (Patient Summary)

patient summary

Ethical and Societal Questions Loom Large as Gene Editing Moves Closer to the Clinic

JAMA Network

 The committee’s next meeting is tentatively scheduled for February 11 and 12 in Washington, DC, and it will include sessions open to the public

Hematuria as a Marker of Occult Urinary Tract Cancer (Lynch Syndrome patients)

Patients referred for AMH have a relatively lower (0.5% to 5.0%) but nontrivial probability of underlying occult cancer (2, 7–15) that is estimated to range from 7% to greater than 20% in higher-risk subgroups in some series (9, 16–18).

 The investigation of hematuria includes radiologic evaluation to identify potential pathology in the upper urinary tract.

upper urinary tract cancer:

open access
 Hematuria as a Marker of Occult Urinary Tract Cancer: Advice for High-Value Care From the American College of Physicians
 
Background: The presence of blood in the urine, or hematuria, is a common finding in clinical practice and can sometimes be a sign of occult cancer. This article describes the clinical epidemiology of hematuria and the current state of practice and science in this context and provides suggestions for clinicians evaluating patients with hematuria.
 
High-Value Care Advice 1: Clinicians should include gross hematuria in their routine review of systems and specifically ask all patients with microscopic hematuria about any history of gross hematuria.
High-Value Care Advice 2: Clinicians should not use screening urinalysis for cancer detection in asymptomatic adults.
High-Value Care Advice 3: Clinicians should confirm heme-positive results of dipstick testing with microscopic urinalysis that demonstrates 3 or more erythrocytes per high-powered field before initiating further evaluation in all asymptomatic adults.
High-Value Care Advice 4: Clinicians should refer for further urologic evaluation in all adults with gross hematuria, even if self-limited.
High-Value Care Advice 5: Clinicians should consider urology referral for cystoscopy and imaging in adults with microscopically confirmed hematuria in the absence of some demonstrable benign cause.
High-Value Care Advice 6: Clinicians should pursue evaluation of hematuria even if the patient is receiving antiplatelet or anticoagulant therapy.
High-Value Care Advice 7: Clinicians should not obtain urinary cytology or other urine-based molecular markers for bladder cancer detection in the initial evaluation of hematuria.

 Hematuria is frequently encountered among adults in ambulatory care (1, 2). Despite the absence of recommendations for hematuria screening (3, 4), millions of patients have urine dipstick testing and microscopic examinations as part of routine primary care practice (5, 6). The frequency of urinalysis with the primary intent of cancer screening is unknown; however, hematuria may often be an incidental finding on tests pursued for other purposes, given the multiplex nature of dipstick tests. Referral series underscore the potential for a positive test result to be the presenting sign of occult cancer, and existing hematuria guidelines emphasize structured urologic investigation related to this risk with endoscopy of the bladder (cystoscopy), imaging, and potentially other diagnostic tests and procedures. However, the magnitude of the risk for underlying cancer varies greatly (7–9), and the quality of evidence informing practice creates uncertainty......

 Hematuria occasionally has a dramatic presentation as grossly visible blood in the urine. Symptomatic gross hematuria with associated flank pain or renal colic is the classic presentation of urinary stone disease, whereas painless gross hematuria has a stronger association with cancer......

Outcomes of Incidental Fallopian Tube High-Grade Serous Carcinoma and Serous Tubal Intraepithelial Carcinoma in Women at Low Risk of Hereditary Breast and Ovarian Cancer

Open access
 

Objectives: The natural history and optimal management of serous tubal intraepithelial carcinoma (STIC), regardless of BRCA status, is unknown. We report the follow-up findings of a series of incidental fallopian tube high-grade serous carcinomas (HGSCs) and STICs identified in women at low risk for hereditary breast and ovarian cancer (HBOC), undergoing surgery for other indications.

Materials and Methods: Cases of incidental STIC and HGSC were identified from 2008. Patients with known BRCA1 or BRCA2 mutations, or a family history of ovarian or breast cancer before the diagnosis of STIC or HGSC were excluded. A retrospective chart review was conducted to obtain clinical data.

Results: Eighteen cases were identified with a median follow-up of 25 months (range, 4-88 months). Twelve of 18 patients had a diagnosis of STIC with no associated invasive HGSC and 6 had STIC associated with other invasive malignancies. Completion staging surgery was performed on 7 of the 18 patients, including 5 of 12 in which there was STIC only identified on primary surgery; 3 cases were upstaged from STIC only to HGSC based on the staging surgery. Recurrence of HGSC occurred in 2 of the 18 patients. BRCA testing was performed on 3 patients, 1 of whom tested positive for a pathogenic BRCA1 mutation.

Conclusions: Our study suggests that completion staging surgery for incidental STICs in non-BRCA patients may be considered. These patients should be offered hereditary testing. The Pelvic-Ovarian cancer INTerception (POINT) Project is an international registry set up to add to our understanding of STICs.

Quality of Life in Women After Pelvic Exenteration for Gynecological Malignancies

open access
 Quality of Life in Women After Pelvic Exenteration for Gynecological Malignancies: A Multicentric Study.

 Women receiving PE for advanced epithelial ovarian cancer were not included in the study.....Patients affected by ovarian cancer have been excluded from the study because of the frequent upper abdominal involvement, which requires an extensive supramesocolic cytoreductive surgery concomitant with PE.

Objectives: This retrospective, multicentric study investigates quality-of-life issues and emotional distress in gynecological cancer survivors submitted to pelvic exenteration (PE).

Methods: The Global Health Status scale of European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30; the EORTC QLQ-CX24 (CX24), and EORTC QLQ-OV28 questionnaires were administered at least 12 months from surgery only in women with no evidence of further recurrence after PE. Statistical analysis was performed by the analysis of variance (for repeated measures.

Results: Ninety-six subjects affected by gynecological malignancies receiving PE were enrolled in the study. Anterior PE was performed in 47 patients (49%), posterior PE was performed in 29 cases (30.2%), and total PE performed in 20 women (20.8%). In 38 cases (39.6%), a definitive colostomy was performed. Urinary diversion with continent pouch was created in 11 patients. (11.5%), whereas in the remaining cases, a noncontinent pouch was reconstructed. Patients showed a significant discomfort in attitude to disease (71.5 +/- 4.7), body image (48.9 +/- 6.4), financial difficulties (56.2 +/- 5.8), gastrointestinal symptoms (constipation, 47.8 +/- 5.1; diarrhea, 62.4 +/- 6.6; appetite loss, 43.6 +/- 6.7), insomnia (64.5 +/- 6.6), Global Health Status (64.6 +/- 3.8), physical functioning (65.8 +/- 4.6), role functioning (58.8 +/- 5.8), and emotional functioning (67.4 +/- 4.2). A higher number of ostomies (hazard rate [HR], 7.613; P = 0.012), the creation of a noncontinent bladder (HR, 8.230; P = 0.009), and of definitive colostomy (HR, 8.516; P = 0.008) emerged as independent predictors of poorer Global Health Status scores. Older age (HR, 11.235; P = 0.003), vaginal/vulvar cancer (HR, 7.369; P = 0.013), total/posterior PE (HR, 7.393; P = 0.013), higher number of ostomies (HR, 7.613; P = 0.012), the creation of a noncontinent bladder (HR, 8.230; P = 0.009), and of definitive colostomy (HR, 8.516; P = 0.008) emerged as independent predictors of lower body image levels.

Conclusions: Long-term psycho-oncological support is strongly recommended. The reduction of ostomies seems the most effective way to improve patients' quality of life.

 .....In this context, it is well known that besides the impact
of cancer diagnosis by itself, the surgical removal of organs
accomplishing reproductive functions significantly affects QoL
in women with gynecological cancer.5 Therefore, it is conceivable
to hypothesize that the impairment of bowel, urinary, and
sexual functions related to mutilating surgical approach, such as
PE, may have profound psychological implications onwomen’s
self-identity and QoL.14,15 However, despite these considerations,
only few experiences have evaluated the QoL of gynecological
cancer patients submitted to PE.16,17.....

December 2015: top page views (Ovarian Cancer and Us) aka. what you are reading

http://ovariancancerandus.blogspot.com/feeds/posts/default

Entry
(U.S.) FDA Grants Multi-Epitope Vaccine Orphan Des... Dec 28, 2015
Science in 2016: Separating the hype from the prom... Dec 23, 2015
Painful Hands and Feet After Cancer Treatment: Inf... Dec 24, 2015
MDcme.ca Course Information Ovarian Cancer Dec 23, 2015
Can Cancer Patients Participate in More Than One C... Dec 22, 2015

Cancer statistics in China, 2015

open access

Table 2. Estimated New Cancer Cases and Deaths (Thousands) by Sex: China, 2015a Ovary  52.1   22.5

--------------------------------------------------------------------------------
Figure 8.

• Open in figure viewer
• Download Powerpoint slide

Trends in Mortality Rates (Age-Standardized to the Segi Standard Population) for Selected Cancers for Females: China, 2000 to 2011.
Data source: 22 population-based Chinese cancer registries.

 

Prior hysterectomy and oophorectomy and incident venous thrombosis risk among postmenopausal women: a population-based, case-control study

Blogger's Note: some stats deleted for ease of reading, see abstract eg. OR,,,

abstract
 

Objective: Hysterectomy and bilateral salpingo-oophorectomy (BSO) are associated with changes in endogenous hormone levels, yet the risk of venous thrombosis (VT) associated with hysterectomy and BSO is incompletely characterized. This study evaluated the risk of incident VT among postmenopausal women associated with combined prior hysterectomy/oophorectomy status and current use of hormone therapy (HT).

Methods: In a case-control study, we identified incident VT cases (n = 1,623) among postmenopausal Group Health Cooperative enrollees without reproductive cancer, defining their "index date" as their VT diagnosis date (1995-2010). Matched controls had not experienced a prior VT (n = 4,480). Multiple logistic regression models estimated adjusted relative risks for VT associated with combinations of prior hysterectomy/oophorectomy status and HT use at the index date.

Results: Compared with women with an intact uterus who were not using HT, there was no suggestion of greater VT risk in women with prior hysterectomy without BSO, whether they were  or were not using HT. Women with prior hysterectomy and BSO who were using HT were not at a greater VT risk, but there was evidence of a 25% greater risk associated with prior hysterectomy with BSO and no current HT use.

Conclusions: Collectively, these and prior data do not suggest a substantial impact of hysterectomy, with or without BSO, on the risk of VT among postmenopausal women.

(financial toxicity) Financial Insolvency as a Risk Factor for Early Mortality Among Patients With Cancer

open access

INTRODUCTION

For the 1.5 million persons diagnosed with cancer each year, financial stress can be protracted and severe. At the extreme end of financial stress are those whose economic situation deteriorates to the point where they must seek protection from creditors. In a previous study, we found that patients are 2.5 times more likely to file for bankruptcy after a cancer diagnosis compared with individuals who have not been diagnosed with cancer.^1....

Weak story on possible new cancer approach passes along news release claims uncritically (pain medication)

HealthNewsReview.org

 Our Review Summary
A very short story explains how an old drug for pain, dicloflenac, might have some new uses in cancer patients. But we found the story lacked a basic explanation of how the researchers measured the benefits of the drug. It also did not include any original reporting and appeared mostly to be a rewrite of the original news release. We understand that short stories – this was 265 words – can’t have everything. But this story could have done a better job.

"Simple" diagnostic tests are never as simple as presented in PR news releases

HealthNewsReview.org

 

Podcast: real harm to real people from health care PR

healthnewsreview

Lancet conference 2016 - Fully Funded Places Offer (20) exp. Feb 15th

Fully Funded Places Offer
 

The Lancet Oncology/Haematology – Fully Funded Places Offer

 

We’re pleased to be able to offer up to 20 fully funded places at Oncology at the Limits 2016
to readers of ‘The Lancet Oncology’ and ‘The Lancet Haematology’.

Chaired by:

• Professor Tariq Enver – Chairman of the UCL Cancer Institute
• Professor Thomas Lynch – Chairman and CEO of the Mass. General Physicians Organization
• Professor Daniel Hochhauser – Co-Director of the Cancer Research UK-UCL Centre

The confirmed programme includes presentations from a host of high profile oncologists from across the world.
The full programme is here.

Your place will be fully funded to include:

• Complimentary entry to all scientific sessions on Thursday, Friday & Saturday
• Two nights accommodation at the 4-star Melia London White House Hotel on Thursday 31st March and Friday 1st April 2016
  (200m from the Royal College of Physicians)
• Breakfasts, Lunches and Dinners within the core conference programme
  (Thursday evening to Saturday afternoon)

Please note, submitting this form does not guarantee a place at the event, the Chairmen will assign places to maintain a pan-tumor and balanced audience profile by February 15th 2016.

Oncology at the Limits is supported by educational grants from the Pharmaceutical Industry

A list of 2016 supporters is at http://www.atthelimits.org/supporters-2016/

Genetic testing for hereditary cancer predisposition: BRCA1/2, lynch syndrome, and beyond

abstract

Highlights

•

Obstetrician/gynecologists and gynecologic oncologists are in a unique position to identify women at increased hereditary risk of cancer

•

Obstetrician/gynecologists and gynecologic oncologists frequently provide preventive options to their high-risk patients such as screening, prophylactic surgery, and chemoprevention

•

Cancer risk assessment is evolving with to include new genes and new multi-gene panel tests for women's hereditary cancer risk

---

Abstract

Obstetrician/gynecologists and gynecologic oncologists serve an integral role in the care of women at increased hereditary risk of cancer. Their contribution includes initial identification of high risk patients, screening procedures like bimanual exam, trans-vaginal ultrasound and endometrial biopsy, prophylaxis via TAH and/or BSO, and chemoprevention. Further, gynecologists also serve a central role in the management of the secondary repercussions of efforts to mitigate increased cancer risks, including vasomotor symptoms, sexual function, bone health, cardiovascular disease, and mental health. The past several years has seen multiple new high and moderate penetrance genes introduced into the clinical care of women at increased risk of gynecologic malignancy. Awareness of these new genes and the availability of new multi-gene panel tests is critical for providers on the front-line of women's health.

Natural products and complementary therapies for chemotherapy-induced peripheral neuropathy: A systematic review

open access

Article Outline

1. 1. Introduction
2. 2. Design
3. 3. Results
   1. 3.1. Natural product studies
      1. 3.1.1. Vitamin E
      2. 3.1.2. Glutamate and glutamine
      3. 3.1.3. Goshajinkigan
      4. 3.1.4. Acetyl-l-carnitine
      5. 3.1.5. Alpha-lipoic acid
      6. 3.1.6. Omega-3 fatty acids
   2. 3.2. Complementary therapy studies
      1. 3.2.1. Acupuncture studies
      2. 3.2.2. Touch therapy studies
      3. 3.2.3. Mind-body practice
      4. 3.2.4. Physical activity
4. 4. Discussion
5. 5. Conclusion
6. Conflict of interest
7. References
8. Biography

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious dose-limiting side-effect without any FDA-approved treatment option. Prior reviews focus mostly on pharmacological interventions, but nonpharmaceutical interventions have also been evaluated. A Web of Science and PubMed database search to identify relevant RCTs from January 2005 to May 2015 included the terms: CIPN, cancer; and supplements, vitamin E, goshajinkigan, kampo, acetyl-l-carnitine, carnitine, alpha-lipoic acid, omega-3, glutamine, or glutamate; or massage, acupuncture, mind-body practice, yoga, meditation, Tai-Chi, physical activity, or exercise. Of 1465 publications screened, 12 RCTs evaluated natural products and one evaluated electroacupuncture. Vitamin E may help prevent CIPN. l-Glutamine, goshajinkigan, and omega-3 are also promising. Acetyl-l-carnitine may worsen CIPN and alpha-lipoic acid activity is unknown. Electroacupuncture was not superior to placebo. No RCTs were published regarding other complementary therapies, although some studies mention positive incidental findings. Natural products and complementary therapies deserve further investigation, given the lack of effective CIPN interventions.

Understanding cognitive processes behind acceptance or refusal of phase I trials

open access  /abstract & pdf (Review)

 

 This review presents two main sections: the first one describes the psycho-cognitive
variables involved in the decision to participate in phase I oncology trials; the second
section relates possible methods and tools to improve patients’ knowledge and
participation.

Meta-analysis of regression of advanced solid tumors in patients receiving placebo or no anti-cancer therapy in prospective trials

Blogger's Note: numerous references to ovarian cancer

open access

Article Outline

1. 1. Introduction
2. 2. Methods
   1. 2.1. Selection of studies
   2. 2.2. Data extraction and clinical end points
   3. 2.3. Statistical analysis
3. 3. Results
   1. 3.1. Search results
   2. 3.2. Overall response and disease control rates
   3. 3.3. Subgroup analysis of response and disease control by histology, baseline progressive disease and line of therapy
   4. 3.4. Publication bias
4. 4. Discussion
5. Role of funding source
6. Relevant disclosures
7. Author contributions
8. References
9. Biography

 Conclusions
Spontaneous regressions are seen across all advanced solid tumors. Some malignancies demonstrated higher rates of spontaneous regressions and may be relatively immunotherapy responsive.

Electronic Health Records : International Health Care System Profiles

Electronic Health Records (international comparisons eg. access)

International Health Care System Profiles - 18 countries

Home

 Across the globe, health care policymakers face mounting pressure to lower costs while improving the quality and safety of care. The U.S. can learn a lot by examining other health systems, their performance in relation to ours, and their health care delivery and payment innovations. This site presents profiles of the health care systems in 18 countries.
 

About This Site

This site presents overviews of the health care systems of Australia, Canada, Denmark, England, France, Germany, Israel, Japan, the Netherlands, New Zealand, Norway, Singapore, Sweden, Switzerland, and the United States. Each overview covers health insurance, public and private financing, health system organization and governance, health care quality and coordination, disparities, efficiency and integration, use of information technology and evidence-based practice, cost containment, and recent reforms and innovations. In addition, the site provides summary data on a number of key health system characteristics and performance indicators, including overall health care spending, hospital spending and utilization, health care access, patient safety, care coordination, chronic care management, disease prevention, capacity for quality improvement, and public views. The site also features results from the latest Commonwealth Fund International Survey of Primary Care Physicians.
The site is an online companion to the Commonwealth Fund's annual International Profiles of Health Care Systems report, edited by Elias Mossialos, Martin Wenzl, Dana Sarnak, and Robin Osborn.
Download the full report [PDF]

Incidental germline variants in 1000 advanced cancers on a prospective somatic genomic profiling protocol

abstract
 

Background Next generation sequencing in cancer research may reveal germline variants of clinical significance. We report patient preferences for return of results and the prevalence of incidental pathogenic germline variants.

Patients and Methods Targeted exome sequencing of 202 genes was performed in 1000 advanced cancers using tumor and normal DNA in a research laboratory. Pathogenic variants in 18 genes, recommended for return by The American College of Medical Genetics and Genomics, as well as PALB2, were considered actionable. Patient preferences of return of incidental germline results were collected. Return of results was initiated with genetic counseling and repeat CLIA testing.

Results Of the 1000 patients who underwent sequencing, 43 had likely pathogenic germline variants: APC (1), BRCA1 (11), BRCA2 (10), TP53 (10), MSH2 (1), MSH6 (4), PALB2 (2), PTEN (2), TSC2 (1), and RB1 (1). 20 (47%) of 43 variants were previously known based on clinical genetic testing. Of 1167 patients who consented for a germline testing protocol, 1157 (99%) desired to be informed of incidental results. 23 previously unrecognized mutations identified in the research environment were confirmed with an orthogonal CLIA platform. All patients approached decided to proceed with formal genetic counseling; in all cases where formal genetic testing was performed the germline variant of concern validated with clinical genetic testing.

Conclusions In this series 2.3% patients had previously unrecognized pathogenic germline mutations in 19 cancer-related genes. Thus genomic sequencing must be accompanied by a plan for return of germline results, in partnership with genetic counseling.

*NEW* search gadget for blog: Ovarian Cancer and Us

Blogger's Note: the old search gadget (right hand side of page) has not been working - the new search gadget seems to work now

Editorial: Reassessing rare cancers

Medical Journal of Australia

 Ovarian cancer shows how genetic subtyping allows similarities between cancers to guide treatment trials

 Our approach to clinical trials will need to be different in rare cancers where large randomised trials are impractical.

Should we routinely screen for ovarian cancer? (read/respond online to this article)

 Cancer newsletter from MD Anderson Cancer Center

 

 .....Which makes a recent announcement from physicians in the United Kingdom so exciting. A large clinical trial demonstrated the effectiveness and life-saving potential of a unique screening method for ovarian cancer. We are cautiously optimistic about the implications of this study for an ovarian cancer-screening program in the United States, but these results must be interpreted in the proper context of risk and reward......

....We may be at a turning point in the search for an effective strategy that decreases deaths by detecting ovarian cancer early. The advocacy community, enriched with passionate survivors and family members who have lost loved ones to ovarian cancer, have fiercely and consistently advocated for directing precious research funds to the discovery and validation of effective screening technologies. Taking time to consider the public health implications of this enormously large trial will help us in carving a rational path forward.

Karen Lu, M.D.
Chair and Professor
Department of Gynecologic Oncology and Reproductive Medicine
MD Anderson Cancer Center

Mark Ebell, M.D.
Professor of Epidemiology
College of Public Health
University of Georgia

NOTE: Dr. Ebell is a member of the United States Preventive Services Task Force (USPSTF). This article does not necessarily represent the views and policies of the USPSTF.

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Lynch Syndrome UK CONFERENCE May 7, 2016

Lynch Syndrome UK 

 The cost for Lynch Syndrome patients and their families will be £10.00 per person. This will be refunded on the day for attendees only. Working within our charity status guidelines, LSUK has taken the decision to heavily subsidise conference tickets to allow as many people as possible to attend on the day. Coffee and lunch will be provided at the venue.

Not only is the conference a great learning opportunity, but you'll also get to meet and chat to people with LS from across the UK. Last year, we're pleased to say, many new friendships were formed amongst the delegates.

Tickets will be limited due to the size of the venue so please book early to avoid disappointment.

We also have a limited number of tickets for Medical Professionals which will be priced at £30.00 per person.

Tickets can be purchased from our Online Shop

Full Program Coming Soon Confirmed  - 24/01/2016

Dr Ian Frayling, Genetics and latest Lynch Syndrome Research
Prof Usha Menon, Professor of Gynaecological Cancer.
Professor Sue Clark, Consultant Colorectal Surgeon
Gill Borthwick, CAPP3 Trial

search: Cochrane Library (Gynaecology Cancer/Ovary)

Cochrane Library (abstracts - newest first)

 Published or updated within the last:

• All dates (37)
• 3 months (6)
• 6 months (6)
• 1 year (7)
• 2 years (14)

Effectiveness of tranexamic acid in reducing blood loss during cytoreductive surgery for advanced ovarian cancer

The Cochrane Library - abstract
 

Published Online: 23 JAN 2016

Assessed as up-to-date: 31 MAY 2015

 

Plain language summary

The issue:
Cytoreductive surgery (also called debulking) is a standard surgical procedure for advanced epithelial ovarian cancer. During surgery, the aim is to remove not only the ovaries, but also the uterus, fallopian tubes, and as much of the visible tumour as possible. Blood loss during cytoreductive surgery has long been recognised as a contributor to prolonged recovery time.
The aim of the review:
We evaluated the effectiveness and safety of tranexamic acid for reducing blood loss during cytoreductive surgery in women with advanced epithelial ovarian cancer. We searched for scientific research studies up to May 2015 and found only one randomised controlled trial ‒ considered the gold standard for study design ‒ that assessed a single dose of tranexamic acid given intravenously before the start of surgery versus a placebo in women undergoing cytoreductive surgery for clinically suspected advanced advanced epithelial ovarian cancer.
What are the main findings and conclusion?
Although tranexamic acid did numerically reduce blood loss, there was no clinical benefit, as the difference in blood loss was minimal, and there was no difference in need for blood transfusion, suggesting that this level of blood loss did not make a difference to the patient's well-being. Additionally, there was incomplete and limited evidence regarding tranexamic acid-related adverse events, so we can say little about whether tranexamic acid is safe for women with advanced ovarian cancer. The evidence we found from a single study was therefore insufficient to support routinely giving prophylactic tranexamic acid for cytoreductive surgery. This review indicates the need for future good quality, well-designed randomised controlled trials to provide more evidence on the effectiveness, safety and appropriate administration of tranexamic acid.
Quality of evidence:
The quality of the evidence was variable; therefore the overall the strength of the evidence reported in this review is low, as it is based on only one small randomised controlled study.

Prognostic factors in Polish patients with BRCA1-dependent ovarian cancer

open access
 

Background

Treatment outcomes appear to be better for ovarian cancer (OC) patients carrying the BRCA1/2 germline mutation than for patients with sporadic OC. However, most published data are for North American, British and Jewish populations. There have been very few studies on treatment outcomes in Central and Eastern European patients with OC. The aim of this study was to analyse prognostic factors in Polish patients with BRCA1-dependent OC (BRCA1-OC). 

 

Conclusion

Prognostic factors for favourable treatment outcomes in Polish patients with BRCA1-OC do not appear to differ from those in patients with sporadic OC. The incidence of the endometrial subtype of OC was relatively high (34.9 %) among women in the study. This was unexpected and has not been reported previously. This subtype of OC was an independent prognostic factor for favourable treatment outcomes.

Estrogen supplements may protect against dementia

science news

Association of Mild Cognitive Impairment With Exposure to General Anesthesia for Surgical and Nonsurgical Procedures: A Population-Based Study

Abstract
 

Objective

To examine whether exposure to general anesthesia for operations and procedures after the age of 40 years is associated with incident mild cognitive impairment (MCI) in elderly patients.

Patients and Methods

A population-based, prospective cohort of Olmsted County, Minnesota, residents aged 70 to 89 years at enrollment, underwent baseline and 15-month interval evaluations that included the Clinical Dementia Rating scale, a neurologic evaluation, and neuropsychological testing. Anesthesia records after the age of 40 years until last evaluation for MCI were abstracted. Proportional hazards regression, adjusting for other known MCI risk factors, was used to assess whether exposure to surgical general anesthesia after the age of 40 years is associated with the incidence of MCI.

Results

Of 1731 participants (mean age, 79 years), 536 (31.0%) developed MCI during a median follow-up of 4.8 years. Anesthesia exposure was not associated with MCI when analyzed as a dichotomous variable (any vs none; adjusted hazard ratio [HR], 1.07; 95% CI, 0.83-1.37; P=.61), the number of exposures (adjusted HR, 1.05; 95% CI, 0.78-1.42; adjusted HR, 1.12; 95% CI, 0.86-1.47; and adjusted HR, 1.02; 95% CI, 0.76-1.34, for 1, 2-3, and ≥4 exposures compared with no exposure as the reference; P=.73), or the total cumulative duration of exposure (adjusted HR, 1.00; 95% CI, 0.98-1.01, per 60-minute increase; P=.83). In secondary sensitivity analyses, anesthesia after 60 years of age was associated with incident MCI (adjusted HR, 1.25; 95% CI, 1.02-1.55; P=.04), as was exposure in the previous 20 and 10 years.

Conclusion

We found no significant association between cumulative exposure to surgical anesthesia after 40 years of age and MCI. However, these data do not exclude the possibility that anesthetic exposures occurring later in life may be associated with an increase in the rate of incident MCI.

Characteristics of Exceptional or Super Responders to Cancer Drugs

abstract
 

Objective

To summarize case reports of exceptional and super responders already published in the biomedical literature.

Patients and Methods

We searched for published case reports or abstracts of exceptional or super responders to a cancer drug using PubMed and Google Scholar search engines. Pooling such reports is widely considered a promising research strategy and the subject of several ongoing investigations, including the National Cancer Institute's Exceptional Responders Initiative. All articles were read in full, including relevant references. We extracted clinical characteristics of exceptional or super responders, including age, tumor type, drug, genetic mutations, depth of response, duration of response, number of previous lines of therapy, duration of response to a previous line of therapy, and the number of patients treated similarly to identify the exceptional case. This study was performed between March 1, 2015, and April 30, 2015.

Results

Among 489 articles, 32 exceptional responders were identified. The most common malignancies described were renal cell cancer (5 of 32 [16%]) and urothelial carcinoma (4 of 32 [13%]). The use of targeted agents was common in these cases (26 of 32 [81%]), particularly inhibitors of the mTOR pathway (16 of 32 [50%]). The median duration of response among responders was 17.5 months, and 59% (19 of 32) of the patients were last known to be alive with continuing response or stable disease. Notably, 46% (12 of 26) of the patients had received 2 or more previous lines of therapy and 6 of the 32 cases (19%) did not report this information. Few authors report the number of patients treated similarly to observe the super response (12 of 32 [38%]).

Conclusion

Exceptional or super responders to cancer drugs have been described in the literature; however, there is incompleteness in the reporting of relevant data that may help clarify whether such responses are secondary to treatment or reflect underlying biology.

Changes in Burnout and Satisfaction With Work-Life Balance in Physicians and the General US Working Population Between 2011 and 2014

abstract

Conclusion

Burnout and satisfaction with work-life balance in US physicians worsened from 2011 to 2014. More than half of US physicians are now experiencing professional burnout.

Biosimilars Webcasts

Biosimilars Webcast

Multiple direct and indirect mechanisms drive estrogen-induced tumor growth in high grade serous ovarian cancers

abstract

The notion that menopausal estrogen replacement therapy increases ovarian cancer risk, but only for the two more common types (i.e. serous and endometrioid), while possibly decreasing risk for clear cell tumors, is strongly suggestive of causality. However, whether estradiol (E2) is tumorigenic or promotes development of occult preexisting disease is unknown. The present study investigated molecular and cellular mechanisms by which E2 modulates the growth of high grade serous ovarian cancer (HGSOC). Results showed that ERα expression was necessary and sufficient to induce the growth of HGSOC cells in in vitro models. Conversely, in vivo experimental studies demonstrated that increasing the levels of circulating estrogens resulted in a significant growth acceleration of ERα-negative HGSOC xenografts, as well. Tumors from E2-treated mice had significantly higher proliferation rate, angiogenesis, and density of tumor-associated macrophage (TAM) compared to ovariectomized females. Accordingly, immunohistochemical analysis of ERα-negative tissue specimens from HGSOC patients showed a significantly greater TAM infiltration in premenopausal compared to postmenopausal women. This study describes novel insights into the impact of E2 on tumor microenvironment, independently of its direct effect on tumor cell growth, thus supporting the idea that multiple direct and indirect mechanisms drive estrogen-induced tumor growth in HGSOC.

Significant frequency of MSH2/MSH6 abnormality in ovarian endometrioid carcinoma supports a histotype-specific Lynch syndrome screening in ovarian

abstract

AIMS:

Lynch syndrome screening in ovarian carcinoma is controversial. This study aims to assess the frequency of deficient mismatch repair protein (dMMR) in a retrospective cohort enriched for non-high-grade serous carcinomas and its association with outcome within histological types.

METHODS AND RESULTS:

Tissue microarrays representing 612 ovarian carcinomas were tested for mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) by immunohistochemistry. dMMR was detected in 13.8% of endometrioid and 2.4% of clear cell carcinomas but none in other histological types. Within endometrioid carcinomas, 11/25 dMMR cases showed abnormal MLH1/PMS2, 10 cases abnormal MSH2/MSH6 and 4 cases isolated abnormal MSH6 indicating that at least 7.7% of endometrioid carcinomas have dMMR probably related to Lynch syndrome. The four dMMR clear cell carcinomas showed abnormal MSH2/MSH6 in three and isolated abnormal MSH6 in one case all probably related to Lynch syndrome. Within endometrioid carcinomas dMMR was significantly associated with age under 50 years, synchronous endometrial endometrioid carcinoma, higher CA125 level at diagnosis, higher FIGO grade, absence of ARID1A and at least 20 CD8 positive intraepithelial lymphocytes per high power field but was not associated with cancer specific death. Age under 50, higher CA125 levels at diagnosis and at least 20 CD8 positive intraepithelial lymphocytes per high power field remained significant after adjusting for multiple testing but their sensitivity to identify dMMR remained insufficient.

CONCLUSION:

Our data support the motion for a histotype-specific Lynch syndrome screening in ovarian carcinoma confined to endometrioid and clear cell carcinomas.

Save Cochrane Canada (petition to Federal Healthcare Minister)

petition

Evidence for Democracy (E4D) has mounted a petition to Health Minister Jane Philpott to restore funding for Cochrane Canada. Please visit https://evidencefordemocracy.ca/en/savecochranecanada to sign the petition and show your support. We would appreciate if you would distribute this information through your networks so they have the opportunity to sign and share, via Twitter and Facebook.

Together, we can #saveCochraneCanada!

 

End-Of-Life Costs in U.S.: Not So High? (research comparisons/critique)

medpage

 An article this week in the Journal of the American Medical Association indicated that in-hospital deaths among cancer patients were lower, and end-of-life costs no higher, in the U.S. than in some other industrialized nations. Sounds reassuring, but in this 150-second analysis, MedPage Today medical reviewer F. Perry Wilson, MD, points up several caveats that undercut the feel-good messages.....

Physician Encourages Colleagues to Take an Objective Look at Cancer Survivorship

Curetoday

 Over the weekend, Smita Bhatia delivered a lecture titled “Long-Term and Late Effects: The Science of Survivorship” at the inaugural 2016 Cancer Survivorship Symposium held in San Francisco.

 ....There has been less attention to bringing back survivors for a head-to-toe comprehensive assessment of all their complications. At the end of the day, we have to understand that we give our cancer patients huge amounts of treatment. We give them a lot of chemotherapy, radiation and other biological agents. We would be naïve to think these treatments don't have any effect on the organ systems — it's important that we follow our survivors long term to understand that impact....

Operability and chemotherapy responsiveness in advanced low-grade serous ovarian cancer. An analysis of the AGO Study Group metadatabase

abstract

Highlights

•

Primary low-grade serous ovarian cancer (LGSOC) is not as responsive to platinum-taxane-based chemotherapy as high-grade serous advanced ovarian cancer (HGSOC)

•

Surgical debulking showed a similar impact on outcome in primary LGSOC and HGSOC however LGSOC were associated with better prognosis

Evaluation of 122 advanced-stage cutaneous squamous cell carcinomas by comprehensive genomic profiling opens the door for new routes to targeted therapies

abstract

CONCLUSIONS
In the current study, approximately 88% of patients with cSCC were found to harbor clinically relevant GAs that have the potential to guide the treatment of patients with advanced-stage tumors with targeted therapeutic agents

Reduced prefrontal activation during working and long-term memory tasks and impaired patient-reported cognition....

abstract (small study)
 Reduced prefrontal activation during working and long-term memory tasks and impaired patient-reported cognition among cancer survivors postchemotherapy compared with healthy controls

CONCLUSIONS

Decreased recruitment of brain regions associated with the encoding of working memory and recognition memory was observed in the oncology patients compared with the control group. These results suggest that there is a reduction in neural functioning postchemotherapy and corroborate patient-reported cognitive difficulties after cancer treatment, although a direct association was not observed.

Individualized Treatment of Patients With Early-Stage Epithelial Ovarian Cancer After Incomplete Initial Surgery

open access

DISCUSSION

Incomplete staging surgery is common in the treatment of ESEOC.⁷ Insufficient preoperative evaluation, lack of specialized skills and experience, as well as neglect of frozen sections contribute to this clinical dilemma.^{6,8,9,23–25} Previous studies revealed obvious risks related to incomplete surgery and recommended restaging surgery as essential treatment for these patients.^3–5,11,12 However, most previous studies focused on the superior outcomes of CSS (comprehensive staging surgery) compared with incomplete surgery, and practical concerns closely related to restaging surgery were seldom considered.²⁶

Factors Affecting Short-term Mortality in Women With Ovarian, Tubal, or Primary Peritoneal Cancer....

open access

 Factors Affecting Short-term Mortality in Women With Ovarian, Tubal, or Primary Peritoneal Cancer: Population-Based Cohort Analysis of English National Cancer Registration Data

.... In this study, we focus on primary invasive epithelial cancer that accounts for the majority of the mortality and extend the analysis to include fallopian tube and primary peritoneal cancers in line with the current theory of ovarian tumorigenesis and the concept of locoregional “pelvic” cancer.⁹ The aim is to quantify mortality in the first year after diagnosis, describe the relationship between various factors and mortality, and identify factors that could be targeted to reduce mortality rates......

 Conclusions: Although our results are based on data from England, they are likely to have implications for cancer care pathways worldwide because most of the identified factors are not specific to the UK health care system. Our results suggest the need to increase symptom awareness, promote timely general practitioner referral, and optimize diagnostic and early treatment pathways within secondary care to increase access to treatment for women with advanced-stage invasive epithelial ovarian, tubal, and primary peritoneal cancer. This process should be pursued alongside continued efforts to develop primary prevention and screening strategies.