Hereditary cancer-associated mutations in women diagnosed with two primary cancers.......

  Blogger's Note: this study does not reflect those whose first diagnosis was not one of the more common cancers in either syndrome

 

Hereditary cancer-associated mutations in women diagnosed with two primary cancers: an opportunity to identify hereditary cancer syndromes after the first cancer diagnosis

"This retrospective analysis focused on women diagnosed with at least two primary cancers who were tested for hereditary cancer mutations in order to determine the prevalence of mutation carriers and to examine the time interval between the two diagnoses. In addition, the number of women who would meet the current NCCN guidelines for genetic testing after their first cancer diagnosis was determined."

 Open access - Myriad Genetics 

Patients Tested at a Laboratory for Hereditary Cancer Syndromes Show an Overlap for Multiple Syndromes in Their Personal and Familial Cancer Histories

 FullText 
 Patients Tested at a Laboratory for Hereditary Cancer Syndromes Show an Overlap for Multiple Syndromes in Their Personal and Familial Cancer Histories


 This supports the value of multigene panels to identify pathogenic mutations in the absence of a clinically specific phenotype.

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Keywords

Hereditary breast and ovarian cancer BRCA1 BRCA2 Lynch syndrome Hereditary cancer syndromes Genetic testing NCCN guidelines Panel testing

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Deficient mismatch repair: Read all about it (Review) Lynch Syndrome

open access

 Affiliations: Department of Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, St. James University Hospital, Leeds, LS9 7TF, UK

• Download PDF

Abstract

Defects in the DNA mismatch repair (MMR) proteins, result in a phenotype called microsatellite instability (MSI), occurring in up to 15% of sporadic colorectal cancers. Approximately one quarter of colon cancers with deficient MMR (dMMR) develop as a result of an inherited predisposition syndrome, Lynch syndrome (formerly known as HNPCC). It is essential to identify patients who potentially have Lynch syndrome, as not only they, but also family members, may require screening and monitoring. Diagnostic criteria have been developed, based primarily on Western populations, and several methodologies are available to identify dMMR tumours, including immunohistochemistry and microsatellite testing. These criteria have provided evidence supporting the introduction of reflex testing. Yet, it is becoming increasingly clear that tests have a limited sensitivity and specificity and may yet be superseded by next generation sequencing. In this review, the limitations of diagnostic criteria are discussed, and current and emerging screening technologies explained. There is now useful evidence supporting the prognostic and predictive value of dMMR status in colorectal tumours, but much less is known about their value in extracolonic tumours, that may also feature in Lynch syndrome. This review assesses current literature relating to dMMR in endometrial, ovarian, gastric and melanoma cancers, which it would seem, may benefit from large-scale clinical trials in order to further close the gap in knowledge between colorectal and extracolonic tumours.

 Contents
1. Introduction
2. dMMR in sporadic colorectal cancer
3. dMMR in Lynch syndrome
4. Who (and how) to test for mismatch repair deficiencies?
5. Does ‘one size’ really fit all?
6. Reflex testing
7. MMR immunohistochemistry (IHC)
8. Microsatellite (MSI) testing
9. Next generation sequencing (NGS)
10. Deficient MMR and clinical outcomes
11. Conclusion

Ovarian Cancer:  .....One feature common to most studies was the fact that there was an overrepresentation of the non-serous tumours within the MSI cohorts, which parallels the overrepresentation of mucinous and endometrioid histologies in CRC and endometrial cancers respectively. In terms of data relating to the effect of dMMR or MSI on prognosis or response to chemotherapy, very little has been published, and the results are varied.....Extracolonic cancers trail far behind in terms of what is known of the prognostic and predictive value of MMR, and, our understanding will remain limited unless large controlled trials are performed.

2015 Conference Slides - Ovarian Cancer National Alliance

2015 Conference Slides

Editorial: BRIP1 as an ovarian cancer susceptibility gene: ready for the clinic?

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This item requires a subscription* to JNCI Journal of the National Cancer Institute.

Full Text (PDF)

BRIP1 as an ovarian cancer susceptibility gene: ready for the clinic? JNCI J Natl Cancer Inst (2015) 107 (11): djv262 First published online August 27, 2015

Germline Mutations in the BRIP1, BARD1, PALB2, and NBN Genes in Women With Ovarian Cancer

abstract

Conclusions: Deleterious germline mutations in BRIP1 are associated with a moderate increase in EOC risk. These data have clinical implications for risk prediction and prevention approaches for ovarian cancer and emphasize the critical need for risk estimates based on very large sample sizes before genes of moderate penetrance have clinical utility in cancer prevention. 

Giant study poses DNA data-sharing dilemma : Nature News

News 

Longwoods eLetter September 1, 2015 sundry topics/Canada/healthcare

eLetter 

 Off the Cuff

Canadian Medical Association urges healthcare strategy for seniors

Aging in Ontario: Using Population-Based Data in the Evaluation of Trends in Health System Use

How is the Aging Population Causing a Transformation in Healthcare?

An Evidence-Based Policy Prescription for an Aging Population

Demand for home healthcare is changing and rising sharply: 25% of Canadians provide informal care to a love one at home

National Post View: On physician-assisted suicide, respect the conscience rights of all

Canadians have an opportunity to be heard on the issue of physician-assisted dying

(2014) HealthcarePapers Vol. 14 No. 1: Physician-Assisted Death

77% of Canadians support assisted suicide, poll shows

Less than a third of doctors willing to aid in assisted dying: CMA poll

Canadian Medical Association still polarized by doctor-assisted deaths

Wait times continue to drag healthcare outcomes down - Are Canadian wait times for hip replacement justified or could they be shortened? by Robert Brown

Wait Time Management Strategies for Scheduled Care: What Makes Them Succeed?

Nursing shortage cost B.C.’s two largest health authorities $70 million in overtime pay last year

Healthy Cities: Edmonton, AB

NIH grants seek best ways to combine genomic information and EHRs

NIH grants 

“The other important component of these grants is implementing what researchers learn about these gene variants into medical settings to improve patient care.”

—Rongling Li, M.D., Ph.D.
Program Director, eMERGE in the Division of Genomic Medicine at NHGRI

Support for Clinicians Involved in Errors and Adverse Events (Second Victims)

AHRQ Patient Safety Network

Multimethod Testing Strategy May Benefit Patients with Lynch Syndrome (PMS2)

Blogger's Note: Myriad had published stats whereby Lynch Syndrome mutation carriers risked a second cancer, any type of Lynch Syndrome cancer, by 50% within the first 15 years of the first cancer dx (search this blog for Myriad - this item was previously posted)

Medical news

.... The role that PMS2 genetic mutations play in Lynch syndrome has been underestimated due to technological hurdles. “PMS2 mutations have been grossly underestimated due to technical difficulties in handling complex genomic structure. A comprehensive approach to unequivocally identify PMS2 mutations remained to be developed,” said lead investigator Lee-Jun C. Wong, PhD, who is with Baylor College of Medicine in Houston....

In January 2009, the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group issued recommendations regarding genetic testing strategies in patients with newly diagnosed colorectal cancer. Although only 2% to 4% of colorectal cancers are due to Lynch syndrome, identification of these individuals is seen as a critical way to improve their own health as well as the health of their blood relatives.
Individuals with Lynch syndrome have a 16% risk of developing a second primary colorectal cancer within 10 years, and first-degree and second-degree family members with Lynch syndrome face a 35% to 45% risk of a new cancer by age 70.
 

References

1. Li J, Dai H, Feng Y, et al. (2015). A Comprehensive Strategy for Accurate Mutation Detection of the Highly Homologous PMS2. The Journal of Molecular Diagnostics, 17(5): 545–553.

- See more at: http://www.oncotherapynetwork.com/cancer-and-genetics/multimethod-testing-strategy-may-benefit-patients-lynch-syndrome?GUID=59A6C40A-05D9-4E87-A0FC-1850E2FF60E0&rememberme=1&ts=01092015#sthash.XlRthxX4.dpuf

.... In January 2009, the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group issued recommendations regarding genetic testing strategies in patients with newly diagnosed colorectal cancer. Although only 2% to 4% of colorectal cancers are due to Lynch syndrome, identification of these individuals is seen as a critical way to improve their own health as well as the health of their blood relatives.
Individuals with Lynch syndrome have a 16% risk of developing a second primary colorectal cancer within 10 years, and first-degree and second-degree family members with Lynch syndrome face a 35% to 45% risk of a new cancer by age 70.

References
    Li J, Dai H, Feng Y, et al. (2015). A Comprehensive Strategy for Accurate Mutation Detection of the Highly Homologous PMS2. The Journal of Molecular Diagnostics, 17(5): 545–553.

In January 2009, the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group issued recommendations regarding genetic testing strategies in patients with newly diagnosed colorectal cancer. Although only 2% to 4% of colorectal cancers are due to Lynch syndrome, identification of these individuals is seen as a critical way to improve their own health as well as the health of their blood relatives.
Individuals with Lynch syndrome have a 16% risk of developing a second primary colorectal cancer within 10 years, and first-degree and second-degree family members with Lynch syndrome face a 35% to 45% risk of a new cancer by age 70.
 

References

1. Li J, Dai H, Feng Y, et al. (2015). A Comprehensive Strategy for Accurate Mutation Detection of the Highly Homologous PMS2. The Journal of Molecular Diagnostics, 17(5): 545–553.

- See more at: http://www.oncotherapynetwork.com/cancer-and-genetics/multimethod-testing-strategy-may-benefit-patients-lynch-syndrome?GUID=59A6C40A-05D9-4E87-A0FC-1850E2FF60E0&rememberme=1&ts=01092015#sthash.XlRthxX4.dpuf

NCI Awards MD Anderson Researcher $4.1M for Ovarian Cancer Sequencing Study | GenomeWeb

NCI 
 Aug 28, 2015

NEW YORK (GenomeWeb) – The National Cancer Institute has recently awarded a five-year, $4.1 million grant to MD Anderson Cancer Center researcher Michelle Hildebrandt to conduct a large-scale sequencing study to identify rare genomic variants associated with inherited ovarian cancer susceptibility.
Through genome-wide association studies, Hildebrandt and collaborators have identified 11 loci associated with ovarian cancer risk and plan to publish an additional six in the coming months, she wrote in her grant's abstract.
"However, these variants combined only explain less than 5 percent of the heritable risk of ovarian cancer," she noted, adding that even when BRCA1 and BRCA2 mutations are taken into account, about 60 percent of familial ovarian cancer cases are unresolved.

.... Given the well-established differences in prognosis between European and African American ovarian cancer patients, Hildebrandt will also sequence the top candidate genes identified in the first experiments in an ongoing study of African American women with the disease.....

Blood Pressure Drugs Linked to Longer Ovarian Cancer Survival (not so fast)

Blood Pressure Drugs 

 Beta Blockers May Boost Ovarian Cancer Survival

But researchers say clinical trials needed to prove older beta blockers lengthen life in these patients

Obama Calls For A Greater Effort To Fight Ovarian Cancer

Obama 

Role of circulating tumor cells in future diagnosis and therapy of cancer

open access - J Cancer Metastasis Treatment

 Circulating tumor cells (CTCs) have become a blistering topic of discussion for oncologists because of their tremendous potential in the diagnosis and treatment of cancer. Over the past few years, they have been doled with quite an amount of research in this area understanding that CTCs are shed from tumors and circulate in the bloodstream. This process can also occur at an early stage of cancer. The major limitation in isolation of CTCs is their availability in limited numbers. Hence, many techniques have been developed and are under continuous improvement to enhance their efficacy of CTC isolation and enumeration. They have shown their potentiality to not just indicate the presence of a tumor but also to provide us with its core information......

.... A study by Kuhlmann et al.^[120] brings to light an importance of the molecular characterization of CTCs in ovarian cancer. They have shown that ERCC1+ CTCs can predict platinum resistance therapy in ovarian cancer which is still remains a big challenge in the treatment of ovarian malignancy. ^[120] Obermayer et al.^[121] have shown that there are more number of cyclophilin C gene (PPIC) positive CTCs are detected usually in ovarian platinum-resistant cancer group as compared to the sensitive group than EpCAM positive CTCs in these patients....

(Peregrine Pharmaceuticals/bavituximab) This Small-Cap Cancer Immunotherapy Developer .......

financial media
 This Small-Cap Cancer Immunotherapy Developer Just Snagged Another Big Partner

.... As announced on Monday in a press release, Peregrine and AstraZeneca will explore their respective cancer immunotherapies -- PS-suppressor bavituximab and anti-PD-L1 checkpoint inhibitor MEDI4736 from AstraZeneca -- in various solid tumor types in a phase 1/1b trial. The phase 1 portion will focus on dose-finding, while phase 1b will examine the safety and efficacy of the combination therapy. Under the terms of the agreement, Peregrine will run the initial study....

The state of advocacy in cancer (journal Gynecologic Oncology)

abstract

 Highlights

•

The largest cancer advocacy groups raised over $1,000,000,000.00 in 2013

•

Enhanced revenue was proportional to increased overhead and investments in fund-raising activities

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Abstract

Non-profit advocacy organizations have been important in raising public awareness, promoting education, and enhancing political activism for issues related to cancer. Grassroots efforts aimed at fund-raising have substantially augmented federal funding for community outreach and research. The objective of this review was to evaluate successful accomplishments of several major non-profit organizations that are focused on cancer. A review of news media, medical literature, and financial records (using GuideStar) was performed to access the organizational structure and productivity of several successful cancer advocacy organizations. Compared to other cancer advocacy groups, the American Cancer Society is the oldest (> 100 years old) and worth the most with net assets of over $1.25 billion dollars and an annual total revenue of over $900 million dollars. The ACS also has the highest overhead at 41%. Most of the gynecologic cancer advocacy groups are approximately 20 years old and have collective total annual revenue of over $17M dollars. The Ovarian Cancer Research Fund has been the most successful at raising funds and building net assets to date while maintaining an overhead of < 10%. The most active and financially successful cancer organizations tend to be older, have higher overhead, spend less on total administration, spend more on fund-raising, have more events (rather than a limited number), and use aggressive social media strategies.

Gynecologic Oncology - September 2015 article Index

Gynecologic Oncologylt

Toxicities and Adverse Drug Reactions Experienced During Anticancer Treatment

open access
  Toxicities and Adverse Drug Reactions Experienced During Anticancer Treatment: It Is Desirable to Consider the Problem Within the International System of Pharmacovigilance

To the Editor:

We read with much pleasure the article by Di Maio et al.¹ (Toxicities and Adverse Drug Reactions Experienced During Anticancer Treatment: It Is Desirable to Consider the Problem Within the International System of Pharmacovigilance) It is quite unusual to deal with articles reporting treatment-related toxicities as experienced and reported by patients in scientific literature. A major strength of this article is the authors' ability to share data with three sponsors. Promoters of clinical trials usually tend to emphasize, for obvious commercial reasons, their effectiveness rather than their negative implications, like adverse effects.^2,3 The authors consistently discussed important issues; however, we would like to add the following considerations that may reinforce their results.

1. The authors highlight the potential for a strong under-reporting of toxicities experienced by patients; this is particularly relevant in the field of 
   oncology⁴..... 
   
   
2. The authors highlight that underestimation of the absolute rate of toxicity is a highly relevant problem for clinicians, patients, and regulatory bodies..... 
   
   
3. The authors report data from three clinical trials........
   
   
4. In our opinion, poor sharing of information and lack of interest among health professionals cause under-reporting of toxicities......
   
   
5. There is a need to pursue postgraduate training or continuing medical education......

REFERENCES

1. 1.↵
   1. Di Maio M,
   2. Gallo C,
   3. Leighl NB,
   4. et al.

   (2015) Symptomatic toxicities experienced during anticancer treatment: Agreement between patient and physician reporting in three randomized trials. J Clin Oncol 33:910–915.

   Abstract/FREE Full Text

    

   Abstract

   Purpose Information about symptomatic toxicities of anticancer treatments is not based on direct report by patients, but rather on reports by clinicians in trials. Given the potential for under-reporting, our aim was to compare reporting by patients and physicians of six toxicities (anorexia, nausea, vomiting, constipation, diarrhea, and hair loss) within three randomized trials.

   
   

   Conclusion Subjective toxicities are at high risk of under-reporting by physicians, even when prospectively collected within randomized trials. This strongly supports the incorporation of patient-reported outcomes into toxicity reporting in clinical trials.

   Footnotes

   • Listen to the podcast by Dr Snyder at www.jco.org/podcasts
   • Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

JCO (open access): Basket Trials

Correspondence

• Basket Trials: Just the End of the First Quarter

  • Albrecht Stenzinger,
  • Wilko Weichert,
  • Jochen K. Lennerz,
  • and Frederick Klauschen

  JCO Sep 1, 2015:2823-2824
  • [Full Text]
  • [PDF]

• Reply to A. Stenzinger et al

  • Anish Thomas,
  • Ariel Lopez-Chavez,
  • and Giuseppe Giaccone

  JCO Sep 1, 2015:2824
  • [Full Text]
  • [PDF]

From Protocols to Publications: A Study in Selective Reporting of Outcomes in Randomized Trials in Oncology

abstract

Conclusion Despite public and reviewer access to protocols, selective outcome reporting persists and is a major concern in the reporting of randomized clinical trials. To foster credible evidence-based medicine, additional initiatives are needed to minimize selective reporting. 

Corrigendum: Primary culture of ovarian surface epithelial cells and ascites-derived ovarian cancer cells from patients

no abstract

Molecular Analysis of Upper Tract and Bladder Urothelial Carcinoma (Lynch Syndrome...)

open access

 Molecular Analysis of Upper Tract and Bladder Urothelial Carcinoma: Results from a Microarray Comparison

 ....Furthermore, there are specific environmental exposures and hereditary syndromes associated with an increased risk of development of UTUC. Patients with Hereditary Nonpolyposis Colorectal Cancer have a defect in DNA repair genes resulting in a hypermutable state. These patients are known to have a 22 fold increased risk of developing UTUC [27].... 

..... This study has a number of limitations. First, the numbers are small given the rarity of the disease. Second, this study was conducted using publically available data and there was no central review of the pathology. Despite these limitations, we believe this is the first study of gene expression comparing UTUC and UCB to find specific examples that upper tract tumors may represent a unique sub-population of urothelial carcinoma.

 Conclusion
By separating upper tract urothelial carcinoma and bladder urothelial carcinoma by T stage in our analysis of microarray data, we were able to detect molecular differences in UTUC when compared to UCB. Differentially expressed genes have immunogenic functions, and were involved in the TNF and HFG pathways. Upper tract tumors tend to over-express luminal genes. One gene highly over-expressed in upper tract urothelial carcinoma, SLITRK6, is the target of an antibody-drug conjugate currently being evaluated in phase I clinical trials.

MRI for discriminating metastatic ovarian tumors from primary epithelial ovarian cancers

Full text 

Aims

To find specific magnetic resonance imaging (MRI) features to differentiate metastatic ovarian tumors from primary epithelial ovarian cancers.

Methods

Eleven cases with metastatic ovarian tumors and 26 cases with primary malignant epithelial ovarian cancers were retrospectively studied. All features such as patient characteristics, MRI findings and biomarkers were evaluated. The differences including laterality, configuration, uniformity of locules, diffusion weighted imaging (DWI) signal of solid components and enhancement of solid portions between metastatic ovarian tumors and primary epithelial ovarian cancers were compared by Fisher’s exact test. Median age of patients, the maximum diameter of lesions and biomarkers were compared by the Mann-Whitney test.

Results

Patients with metastatic ovarian tumors were younger than patients with primary epithelial ovarian cancers in the median age (P = 0.015). Patients with bilateral tumors in metastatic ovarian tumors were more than those of primary epithelial ovarian cancers (P = 0.032). The maximum diameter of lesions in metastatic ovarian tumors was smaller than that of primary epithelial ovarian cancers (P = 0.005). The locules in metastatic ovarian tumors were more uniform than those of primary epithelial ovarian cancers (P = 0.024). The enhancement of solid portions in metastatic ovarian tumors showed more moderate than that of primary epithelial ovarian cancers (P = 0.037). There was no statistically significant difference between the two groups in configuration, DWI signal of solid components and ascites. Biomarkers such as CA125 and human epididymis protein 4 (HE4) in metastatic ovarian tumors showed less elevated than that of primary epithelial ovarian cancers.

Conclusions

Significant differences between metastatic ovarian tumors and primary epithelial ovarian cancers were found in the median age of patients, laterality, the maximum diameter of lesions, uniformity of locules, enhancement patterns of solid portions and biomarkers. Metastatic ovarian tumors usually presented in the younger patients, smaller-sized, more bilateral lesions, more uniform of locules, more moderate enhancement of solid portions, and less elevated levels of CA125 and HE4 than those of primary epithelial ovarian cancers.

Background

The optimal management and prognosis of metastatic ovarian tumors depend on the origin of the primary tumor [1], [2].

Successful use of next generation genomic sequencing (NGS)-directed therapy of clear cell carcinoma of the ovary

open access
 Successful use of next generation genomic sequencing (NGS)-directed therapy of clear cell carcinoma of the ovary (CCCO) with trametinib and metformin in a patient with chemotherapy-refractory disease

 Background

Clear cell carcinoma of the ovary (CCCO) represents a distinct histopathologic subtype [1] comprising 3.7–12.1 % of epithelial ovarian carcinoma (EOC). In general, CCCO has earned notoriety for being a particular challenge for management characterized by higher recurrence rates among patients with early stage disease, poor responsiveness to chemotherapy, especially platinum [2–7], de novo drug resistance, and inferior survival compared to other subtypes of EOC [8]. In light of these characteristics, many investigators have opined that CCCO deserves a unique treatment strategy as a distinct disease entity. Nevertheless, current guidelines recommend similar adjuvant treatment regimens as used for other EOC histologies....

....This patient was fortunate to gain access to a drug that is usually unavailable to ovarian cancer patients due to strict payor policies that follow the drug license to the letter. However, over-zealous regulatory behavior and wholesale restriction of physician prescribing can deprive patients of life-saving medicines. In an era when molecular insights have theranostic value that can outperform the limitations of standard therapeutic options, molecular tumor boards to determine the appropriateness of novel therapies could help patients access breakthrough approaches whose availability is hampered by the regulatory mechanism, but which are nevertheless readily available and tailor made for their individual cancers.....

 (The term “theranostics” was coined to define ongoing efforts in clinics to develop more specific, individualized therapies for various diseases, and to combine diagnostic and therapeutic capabilities into a single agent.)

PARP Inhibition--The New Frontier in Recurrent Ovarian Cancer: Highlights and Perspectives From Chicago

 Note: discusses the different clinical trials (PARP drugs)

Medscape CME

Bradley J. Monk, MD; Thomas J. Herzog, MD

CME Released: 08/28/2015 ; Valid for credit through 08/28/2016

print version (text)

Comparison of the prognosis and recurrence of apparent early-stage ovarian tumors treated with laparoscopy and laparotomy

Full text

 Comparison of the prognosis and recurrence of apparent early-stage ovarian tumors treated with laparoscopy and laparotomy: a meta-analysis of clinical studies

Article selection criteria

All clinical studies that explored the differences in prognosis and/or recurrence of apparent early-stage ovarian tumors (stage I and stage II, according to the FIGO classification) treated with laparotomy versus laparoscopy were considered eligible for the analysis......

 ....Nonetheless, studies examining the effects of laparoscopy versus laparotomy in treating apparent early-stage ovarian cancer have involved limited numbers of patients, and randomized controlled trials are not available. The present review systematically combines existing clinical studies that compared the effects of laparoscopy versus laparotomy in treating apparent early-stage ovarian cancer to evaluate the prognosis and recurrence of laparoscopy and reach a conclusion with high credibility.

..... A limitation of the current study is the small number of studies and the limited numbers of participants involved. This reflects the paucity of high-quality clinical trials that address the efficacy of laparoscopic surgery for treating ovarian tumors. Generalizations of this study’s conclusions to all patients with early-stage ovarian tumors should be considered with caution, and there is still considerable need for higher quality studies with relatively larger sample sizes to address this topic.....

 Conclusion

In conclusion, this meta-analysis confirms that laparoscopy has favorable prognostic outcomes in terms of the postoperative complications rate and the lengths of post-operative hospital compared with conventional laparotomy in the treatment of apparent early-stage ovarian tumors. Laparoscopic surgery may be effective and feasible for treating apparent early-stage ovarian tumors.

Federal party statements on physician assisted dying - Dying With Dignity Canada

Federal party statements on physician assisted dying - Dying With Dignity Canada

 

Read how the major federal parties say they plan to do to respond to the Supreme Court's decision on physician assisted dying.

Dying With Dignity Canada supporters across the country ask us every passing day: What are the official positions of the major federal parties on physician assisted dying?

• Related: Support for assisted dying is growing among Canadian voters: poll
• Act now: Pledge to participate in the federal consultation on assisted dying

So, after the election was called in early August, we reached out to the big players — the Conservatives, the Liberals, the NDP and the Greens — and asked them to provide us with a statement on their plans to respond to the Supreme Court’s February decision to strike down the Criminal Code ban on physician assisted dying. Here’s an excerpt of what we told them:

“For many of our supporters, particularly those in urban and suburban ridings, this is an issue that could be the deciding factor in how they cast their ballots this fall. We will be mobilizing our supporter base in the coming weeks to ask political candidates in their riding to take a pledge in support of the implementation of the letter and spirit of the Carter case. We will be publicizing the names of candidates who take the pledge and those who do not. We request that you provide us with a written policy statement outlining the your party’s on the implementation of physician assisted dying with regards to the Carter case for the right to die with dignity.”

So far, we’ve received responses from the Liberals and the NDP. We have yet to hear from the Conservatives and the Green Party. (Though the Greens, to their credit, have a policy on assisted dying posted to their website.) Of course, we’ll post the outstanding responses if and when they’re sent our way.
The statements, published in both official languages, are available for download below. We hope you find them helpful as you consider how to vote on October 19.

• Liberal Party of Canada position statement on physician assisted dying: (English / French)
• New Democratic Party position statement on physician assisted dying: (English / French)

Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer

open access

Index

Abstract

INTRODUCTION

FAMILIAL CRC WITH DEFECTIVE DNA MISMATCH REPAIR

FAMILIAL CRC WITH INTACT DNA MISMATCH REPAIR

CONCLUSION

References

 Core tip: Clinical criteria and phenotypic presentation of patients and families with hereditary non-polyposis colorectal cancer (HNPCC) do not adequately differentiate the several genetic diseases now classified under HNPCC. Tumor analysis for microsatellite instability (MSI) can dichotomize for the clinician conditions with MSI or without MSI, allowing a focused differential diagnosis. Individual or panel germline genetic testing can further differentiate HNPCC into its genetically defined syndromes or its phenocopies.

Bleomycin-Induced Pneumonitis in the Treatment of Ovarian Sex Cord-Stromal Tumors

abstract: Bleomycin-Induced Pneumonitis in the Treatment of Ovarian Sex Cord-Stromal Tumors: A Systematic Review and Meta-analysis

OBJECTIVE:

Adult ovarian sex cord-stromal tumors (SCSTs) are a rare histological subtype of ovarian cancer associated with a favorable prognosis. Bleomycin-containing regimens are standards of care, although pneumonitis may cause potentially fatal dose-limiting toxicity. We aimed to evaluate the safety of bleomycin in SCST treatment.

METHODS:

We performed a systematic literature review of all studies of bleomycin therapy for SCSTs that were referenced in MEDLINE (PubMed), EMBASE, and Cochrane Central Register of Controlled Trials and published from 1986 to 2014.

RESULTS:

Eight studies totaling 221 patients were included. Rates of pneumonitis (7.7%; 95% confidence interval, 4.2-11.2) and mortality (1.8%; 95% confidence interval, 0.1-3.6) related to bleomycin were significant. However, these results were very similar to those reported for men who were treated with bleomycin for a male germ cell tumor, suggesting that women with ovarian SCSTs are not particularly vulnerable to bleomycin lung toxicity. The main risk factors of bleomycin-induced pneumonitis are high cumulative bleomycin dose (>400 U or mg), age older than 40 years, and impaired renal function. Whether granulocyte colony-stimulating factor is a risk factor remains controversial.

CONCLUSIONS:

Bleomycin-induced pneumonitis frequently occurs in patients with SCSTs and lacks effective treatment. Prevention lies in limiting cumulative bleomycin dose, monitoring pulmonary function during treatment, discontinuing bleomycin at the onset of pulmonary symptoms or if pulmonary function is impaired, and avoiding bleomycin in older patients.

Hormone therapy for ovarian cancer survivors: systematic review and meta-analysis

abstract
 

OBJECTIVE:

Hormone therapy (HT) alleviates menopausal symptoms, but there is a lack of consensus regarding its use among premenopausal ovarian cancer survivors.

METHODS:

We systematically reviewed the literature and searched the Medline (1966-2014), Scopus (2004-2014), Popline (1974-2014), ClinicalTrials.gov (2008-2014), and Cochrane Central Register of Controlled Trials CENTRAL (1999-2014) databases and the reference lists of electronically retrieved studies. Statistical meta-analysis was performed using RevMan 5.1 software.

RESULTS:

Six studies were included in our systematic review, which involved 1,521 women. Among them, 451 women (29.6%) received HT, whereas the remaining 1,070 women (70.4%) did not receive any treatment. We noticed a statistically significant reduction of ovarian cancer-related deaths among women who received HT (odds ratio, 0.47; 95% CI, 0.28-0.80); however, disease recurrence rates did not differ between the two groups (odds ratio, 0.71; 95% CI, 0.45-1.14). Studies included in the present systematic review did not report a significant difference in overall survival and disease-free survival rates among women receiving HT and controls.

CONCLUSIONS:

Based on the results of meta-analysis, HT does not influence the odds of ovarian cancer recurrence; however, this conclusion must be confirmed separately because of significant limitations in the methodological quality of the studies included.

Olaparib in the management of ovarian cancer

Open access

Ovarian cancer mortality and industrial pollution

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.

Women with double primary cancers of the colorectum & endometrium: do they have Lynch syndrome?

abstract
 

Objective

The aim of this study was to determine the clinical characteristics of women with double primary cancers of the colorectum and endometrium and assess the probability of Lynch syndrome.

Study design

We identified 15 women with paraffin-embedded blocks available who were diagnosed, treated and followed for double primary colorectal and endometrial cancers at in a single institution (Korea) between 1994 and 2014. If there was a family history that met the revised Amsterdam criteria for Lynch syndrome, the woman was considered to have ‘clinically defined Lynch syndrome’. If immunohistochemical (IHC) loss of expression of mismatch repair genes (MLH1, MSH2, MSH6, or PMS2) or high microsatellite instability (MSI) was demonstrated in molecular testing, the case was considered ‘suspected Lynch syndrome’.

Results

The incidence of clinically defined Lynch syndrome according to the revised Amsterdam criteria was 66% (8 of 15). All 8 of the women clinically diagnosed with Lynch syndrome had either abnormal IHC loss or MSI-high, indicating a suspected Lynch syndrome. Furthermore, 27% (4 of 15) experienced second primary colorectal cancer or other Lynch syndrome-related cancers. Overall, 66% (10 of 15) met the criteria for clinically defined Lynch syndrome or suspected Lynch syndrome.

Conclusions

Based on our findings, a large percentage (66%) of women with double primary cancers of the colorectum and endometrium are likely to be diagnosed with Lynch syndrome.

Randomized study of sequential cisplatin-topotecan/carboplatin-paclitaxel vs carbo-paclitaxel: effects on QOL

abstract
 Randomized study of sequential cisplatin-topotecan/carboplatin-paclitaxel versus carboplatin-paclitaxel: effects on quality of life.

BACKGROUND:

A recent phase III trial compared the efficacy of cisplatin-topotecan (a topoisomerase I inhibitor) followed by carboplatin-paclitaxel (Arm 1) versus paclitaxel-carboplatin (Arm 2) in women with newly diagnosed stage IIB or greater ovarian cancer. There was a significantly lower response rate in the experimental arm compared to standard treatment, and less likelihood of normalized CA125 within the first 3 months. At 43 months follow-up, there were no significant group differences in progression-free survival. There were also significantly more side effects in the experimental arm.

Evaluation of the Hematologic Safety of Same Day Versus Standard Administration (24- to 72-Hour Delay) of Pegfilgrastim

 febrile neutropenia (FN)
 

abstract/open access
 Evaluation of the Hematologic Safety of Same Day Versus Standard Administration (24- to 72-Hour Delay) of Pegfilgrastim in Gynecology Oncology Patients Undergoing Cytotoxic Chemotherapy

..... The current data available on efficacy and safety on pegfilgrastim administration appear to be variable and based on several factors, including tumor types, disease sites, and chemotherapy regimens. The literature appears to be inconclusive overall. Our study sought to determine the safety and efficacy of pegfilgrastim administration scheduling in a population of women with gynecologic malignancies, and the results of this investigation have a potentially overarching impact on the primary and secondary prophylaxis of FN in this disease group. These results demonstrate no increased risk for the development of FN associated with pegfilgrastim administration on the same day as chemotherapy. However, the incidence of FN was low, and the aRRs could not be calculated. This is particularly exciting for the outpatient treatment of gynecologic malignancy in patients required to travel large distances to and from their treating facilities as it will eliminate a clinic visit. This change in practice to same-day administration of pegfilgrastim has potential financial ramifications, but further investigation is needed before this can be confirmed. Definitive evidence to support same-day administration of pegfilgrastim can be provided only with a prospective study. However, our findings support that same-day administration of pegfilgrastim is not inferior to standard administration in terms of treatment delay; however, this cannot be said for dose modification and hematologic toxicities. Our results support the option of same-day dosing to clinicians and patients who accept a possible decrement in dose modification and hematologic toxicity in exchange for convenience of administration. These data do contribute to the existing literature and can be utilized to support same-day use, which may improve patient satisfaction without compromising timing of delivery of treatment, an important goal of health care administration.

European Network of Gyn Oncological Trial Groups’ Requirements

abstract/open access

 European Network of Gynaecological Oncological Trial Groups’ Requirements for Trials Between Academic Groups and Industry Partners—First Update 2015

 Abstract: The first version of ENGOT’s Requirements for Trials Between Academic Groups and Industry Partners in Europe was published 2010. This first update integrates the experiences made by the ENGOT network and the cooperative group studies while performing, analyzing, and publishing -among others - three large phase III trials. Furthermore, progress in European legislation and its impact on clinical studies in Europe have been considered in this update process.

Laparoscopic Debulking Surgery in the Management of Advanced Ovarian Cancer After Neoadjuvant Chemotherapy

abstract/open access

Abstract

Objective: The purpose of this study was to evaluate the feasibility and morbidity of total laparoscopic debulking surgery in the treatment of advanced ovarian cancer after neoadjuvant chemotherapy.

Differences in Clinical and Biological Features Between Type I and Type II Tumors in FIGO Stages I-II Epithelial Ovarian Carcinoma

Dabstract/open access

Objective: The objective of this study was to compare immunohistochemical profile for the apoptosis regulators p53, C-MYC, bax, PUMA, and PTEN and the cell cycle regulatory proteins p21 and p27, as well as clinical factors between types I and II tumors.

Methods: In total, 131 patients in FIGO (International Federation of Gynecology and Obstetrics) stages I-II were divided into 2 groups of patients after type I tumors (n = 79) and type II tumors (n = 52). Differences in the immunohistochemical profile for the cell cycle–related proteins, detected by tissue microarrays and immune-histochemistry, were compared.

Tyrosine Kinase Inhibitors as Potential Therapeutic Agents in the Treatment of Granulosa Cell Tumors of the Ovary

abstact/open access
 

Abstract

Objective: Granulosa cell tumors of the ovary (GCTs) represent a specific subset of malignant ovarian tumors, of which there are 2 distinct subtypes, the juvenile and the adult form. Aside from surgery, no reliable therapeutic options currently exist for patients with GCT. This study sought to investigate the potential role of small molecule tyrosine kinase inhibitors (TKIs) as novel therapeutics in the clinical management of GCT.

Materials and Methods: Using TKI with distinct but overlapping multitargeted specificities, cellular proliferation, viability, and apoptosis were evaluated in 2 human GCT-derived cell lines, COV434 and KGN.

Results: Sunitinib, which targets the imatinib-inhibited tyrosine kinases of VEGFR, KIT, PDGFR, and FLT-3, was without effect in COV434 and KGN cell lines. Sorafenib, which has a high affinity for RAF1 and BRAF, dose dependently inhibited cellular proliferation and viability in both cell lines at concentrations equivalent to that seen in other systems.

Impact of Age on 30-Day Mortality and Morbidity in Patients... : International Journal of Gynecological Cancer

abstract/open access

Abstract

Objective: To examine the effect of age on postoperative 30-day morbidity and mortality after surgery for ovarian cancer.

Methods: The American College of Surgeons National Surgical Quality Improvement Program files were used to identify patients with ovarian cancer who underwent surgery in 2005 to 2011. Women were divided into 4 age groups: <60, 60 to 69, 70 to 79, and ≥80 years. Multivariable logistic regression models were performed.

Survival of Patients With Mucinous Ovarian Carcinoma and Ovarian Metastases: A Population-Based Cancer Registry Study

abstract/open access

Abstract

Objectives: Patients with mucinous ovarian carcinoma (MOC) generally have a favorable prognosis, although in advanced stage, prognosis is significantly worse compared to patients with serous ovarian carcinomas (SOCs). This might be due to the difficulties in distinguishing MOC from metastatic tumors. In the current study, we investigate prognosis of MOC compared to other types of ovarian cancer and to synchronous metastases to the ovary (sMO).

Should All Cases of High-Grade Serous Ovarian, Tubal, and Primary Peritoneal Carcinomas Be Reclassified as Tubo-Ovarian Serous Carcinoma?

abstract/open access

Abstract

Introduction: The dualistic theory of ovarian carcinogenesis proposes that epithelial “ovarian” cancer is not one entity with several histological subtypes but a collection of different diseases arising from cells of different origin, some of which may not originate in the ovarian surface epithelium.

Methods: All cases referred to the Pan-Birmingham Gynaecological Cancer Centre with an ovarian, tubal, or primary peritoneal cancer between April 2006 and April 2012 were identified from the West Midlands Cancer Registry. Tumors were classified into type I (low-grade endometrioid, clear cell, mucinous, and low-grade serous) and type II (high-grade serous, high-grade endometrioid, carcinosarcoma, and undifferentiated) cancers.

Results: Ovarian (83.5%), tubal (4.3%), or primary peritoneal carcinoma (12.2%) were diagnosed in a total of 583 woman. The ovarian tumors were type I in 134 cases (27.5%), type II in 325 cases (66.7%), and contained elements of both type I and type II tumors in 28 cases (5.7%). Most tubal and primary peritoneal cases, however, were type II tumors: 24 (96.0%) and 64 (90.1%), respectively. Only 16 (5.8%) of the ovarian high-grade serous carcinomas were stage I at diagnosis, whereas 240 (86.6%) were stage III+. Overall survival varied between the subtypes when matched for stage. Stage III low-grade serous and high-grade serous carcinomas had a significantly better survival compared to clear cell and mucinous cases, P = 0.0134. There was no significant difference in overall survival between the high-grade serous ovarian, tubal, or peritoneal carcinomas when matched for stage (stage III, P = 0.3758; stage IV, P = 0.4820).

Conclusions: Type II tumors are more common than type I and account for most tubal and peritoneal cancers. High-grade serous carcinomas, whether classified as ovarian/tubal/peritoneal, seem to behave as one disease entity with no significant difference in survival outcomes, therefore supporting the proposition of a separate classification of “tubo-ovarian serous carcinoma”.

Follow-up in Gynecological Malignancies: A State of Art (open access)

 GENERAL ISSUES

The main concerns about follow-up could be summarized as: Who? When? How? And What?

abstract/full text

Article Tools - open access:

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 Abstract

Objective: The main purpose of this article is to explore the current practice for follow-up of gynecological cancer, pointing out the different procedures, to determine the most clinically and cost-effective surveillance strategies after the primary treatment.

Materials and Methods: We analyzed the follow up strategies for ovarian, endometrial, and cervical cancer. All of the topics discussed below arose from the “ESGO State of Art Conference—Follow-up in gynaecological malignancies” in Turin, (September 11–13, 2014; http://torino2014.esgo.org/).

Results: Physical but these practices should be integrated with biomarkers or imaging strategies. Currently, most recommendations about follow-up are based on retrospective studies and expert opinion, and there is some disagreement on surveillance strategies due to lack of evidence-based knowledge.

Conclusions: All surveillance procedures should be evidence-based with a clearly defined purpose: there is a need for prospective studies to compare the effectiveness of different follow-up regimens measuring overall survival, detection of recurrence, quality of life (QoL), and costs as outcomes.

Economic Considerations on the Follow-Up Practice in Gynecologic Cancers: Few Lights and Many Shadows From a Literature Review

open access/open access

Article Tools- open access:

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 Abstract

Objective: The aim of this review was to analyze the existing literature on the cost of follow-up in gynecology oncology.

Methods/materials: We performed a literature search in Medline and NHS CRD (University of Oxford) databases.......

Results: Finally, the reviewing process selected 2 studies on gynecologic cancers in general, including uterine and ovarian cancers, 3 specific on ovarian cancer, 7 on endometrium, and 9 on cervix. The identified economic literature on economic evaluation of gynecologic cancer follow-up procedures showed to be based on weak evidence of effectiveness and to lack formal methodological approaches. In general, such literature is quite recent, relies on small sample observational studies, and suffers from a lack of financial support.

Conclusions: There are few available lights in economic considerations on gynecologic cancer follow-up, represented by all the published studies, and many shadows that require to be clarified by properly designed randomized trials including cost-effectiveness analysis.

A Patient`s History of Medicine | Health and Everything

blog

Ureteric Injury Risk With Hysterectomy Up 2001 to 2010

health news / abstract

Changes in BMI in long-term childhood cancer survivors (underweight)

abstract

 CONCLUSIONS
The BMI at diagnosis is one of the most important predictors for the BMI at follow-up, and this suggests an important genetic or environmental cause. Adult CCSs are at high risk for developing severe underweight at follow-up. Future studies should focus on the causes and clinical consequences of underweight.

Mayo Clinic researchers find new code that makes reprogramming of cancer cells possible (PLEKHA7)

press release