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Monday, November 14, 2016

Reminder: AICR on Facebook (live) 5:15 pm EST Nov 14th



Don't Miss the 2016 AICR Research Conference

Join us for our 2016 AICR Research Conference tonight on Facebook Live at 5:15 p.m. (EST).
By joining our 25th conference, you'll learn about emerging research in cancer prevention and treatment through nutrition, physical activity and weight management.
We invite you to tune in tonight on Facebook Live to hear several researchers present their study findings on cancer research. Simply click the button below at 5:15 p.m.
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OA: Response to the letter of Fagotti et al. regarding the manuscript: “Pattern of and reason for postoperative residual disease in patients with advanced ovarian cancer following upfront radical debulking surgery”



open access:
Response to the letter of Fagotti et al. regarding the manuscript: “Pattern of and reason for postoperative residual disease in patients with advanced ovarian cancer following upfront radical debulking surgery”


We thank Fagotti et al. for their interest in our paper describing the patterns and sites.
of residual disease (RD) in patients with advanced ovarian cancer who have undergone primary debulking surgery (PDS) (Heitz et al., 2016) in an expert referral center.....
Not a single chemotherapy trial would ever have been accepted if the dose intensity or protocol completion rate achieved had been at such low ranges similar to the low complete resection rates described in the NACT-IDS trials.
In any case, the fate of a patient should not depend on through which door she enters – Rome or Essen or elsewhere. Rather robust quality improvement criteria and strategies should be implemented in all centers performing this kind of treatments. Fagotti et al. have their merits by assessing the value of laparoscopy in this setting, our focus lies rather on other areas but nevertheless each of us has a small piece to contribute to the bigger picture.
 References
    • Ataseven et al., 2016a
    • Prognostic Impact of Port-Site Metastasis After Diagnostic Laparoscopy for Epithelial Ovarian Cancer
    • Ann. Surg. Oncol., 12 (2016) (Jul,PubMed PMID: 27406097)
    • Ataseven et al., 2016b
    • Impact of Abdominal Wall Metastases on Prognosis in Epithelial Ovarian Cancer
    • Int. J. Gynecol. Cancer (2016) (Sep 19. PubMed PMID: 27654263)
    • Fagotti et al., 2016
    • Phase III randomised clinical trial comparing primary surgery versus neoadjuvant chemotherapy in advanced epithelial ovarian cancer with high tumour load (SCORPION trial): Final analysis of peri-operative outcome
    • Eur. J. Cancer, 59 (2016), pp. 22–33 (PubMed PMID: 26998845, May)
    • Article
      |
       PDF (658 K)
      |
      View Record in Scopus
    • Harter et al., 2011
    • Impact of a structured quality management program on surgical outcome in primary advanced ovarian cancer
    • Gynecol. Oncol. (2011) (Mar 16. PubMed PMID: 21414656. Eng.)
    • Heitz et al., 2016
    • Pattern of and reason for postoperative residual disease in patients with advanced ovarian cancer following upfront radical debulking surgery
    • Gynecol. Oncol. (2016) (Mar 24. PubMed PMID: 26975900)
    • Vergote et al., 2010
    • Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer
    • N. Engl. J. Med., 363 (10) (2010), pp. 943–953 (PubMed PMID: 20818904. eng. Sep 2)
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(eg. ovarian cancer) Routine pelvic examinations: A descriptive cross-sectional survey of Women's attitudes and beliefs after new guidelines



abstract
  
Highlights
•
Participants mainly described pelvic examinations as respectful and reassuring
•
A majority incorrectly believed pelvic examinations were useful in detecting ovarian cancer
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A majority incorrectly believed they were needed for sexually transmitted infection screening
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A majority incorrectly believed the examinations were necessary before initiating contraception
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Reading the guideline, fewer women planned to continue yearly pelvic examination

Routine pelvic examinations have been a fundamental part of the annual female examination. The 2014 American College of Physicians (ACP) guideline recommends against routine pelvic examinations in asymptomatic, nonpregnant, average-risk women. Our aim was to evaluate women's attitudes and beliefs about pelvic examinations and how knowledge of the new guidelines contributes to attitudes and beliefs. A descriptive cross-sectional study was performed using a self-administered written survey developed through literature review and pretested and revised on the basis of staff suggestions. Nonpregnant women age ≥ 21 years presenting to outpatient clinics at Mayo Clinic in Arizona or Mayo Clinic in Rochester, Minnesota, received the survey. After being asked about pelvic examination practices and beliefs, participants were informed of the ACP guideline, to determine effect on attitudes and beliefs. Demographic characteristics and pertinent medical history questions were collected from participants. In total, 671 women who were predominantly white, married, and educated completed surveys. Participants described pelvic examinations as reassuring, and a majority believed the examinations were useful in detecting ovarian cancer (74.6%), necessary for screening for sexually transmitted infections (STIs) (71.0%), or necessary before initiating contraception (67.0%). After reading the 2014 ACP guideline, significantly fewer women planned to continue yearly pelvic examinations (P < 0.001). Despite evidence to the contrary, women believed pelvic examinations were necessary for STI screening, contraception initiation, and ovarian cancer detection. After education on the ACP screening guideline, fewer women planned to continue yearly pelvic examinations.
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Saturday, November 12, 2016

(blog) Ovarian Cancer and Us: what, who and how - your interests- this week (top 10)



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#10. Proposed settlement reached in diluted chemo drug ...

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Current perspectives on recommendations for BRCA genetic testing in ovarian cancer patients - European Union



abstract

Highlights

  • •Offer BRCA genetic testing to all invasive epithelial OC patients (excluding borderline and mucinous cancers).
  • •Testing should be irrespective of age.
  • •Ideally offer testing at diagnosis, although patients can be referred at any stage.
  • •Retrospective testing should be offered to patients in long-term follow-up.
  • •Tumour testing should be considered in non-germline-mutated patients.

Abstract

Traditionally, BRCA genetic testing has been undertaken to identify patients and family members at future risk of developing cancer and patients have been referred for testing based on family history. However, the now recognised risk of ovarian cancer (OC) patients, even those with no known family history, harbouring a mutation in BRCA1/2, together with the first poly adenosine diphosphate ribose polymerase inhibitor (PARPi; olaparib [Lynparza]) being licenced for the treatment of BRCA-mutated OC, has led to reconsideration of referral criteria for OC patients. Provided here is a review of the existing data and guidelines in the European Union, relating to recommendations, as well as considerations, for the referral of OC patients for BRCA genetic testing. Based on this review of newly updated guidance and up-to-date evidence, the following is recommended: all patients with invasive epithelial OC (excluding borderline or mucinous), including those with fallopian tube and peritoneal cancers, should be considered as candidates for referral for BRCA genetic testing, irrespective of age; genetic testing should ideally be offered at diagnosis, although patients can be referred at any stage; retrospective testing should be offered to patients in long-term follow-up because of the implications for family members and individual future breast cancer risk; and germline BRCA testing of a blood/saliva sample should initially be conducted and, if negative, tumour tissue should be tested (to identify non-germline [somatic] BRCA PARPi therapy candidates).
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(2013) Wrong chemotherapy doses given to nearly 1,000 cancer patients in Ontario | Toronto Star



Wrong chemotherapy doses given to nearly 1,000 cancer patients in Ontario | Toronto Star
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Proposed settlement reached in diluted chemo drug class action | Toronto Star



Proposed settlement reached in diluted chemo drug class action

 Nov 11, 2016
Toronto Star

A class-action lawsuit representing more than 1,000 cancer patients in Ontario and New Brunswick who were given diluted chemotherapy drugs has reached a proposed settlement.
Mississauga-based drug supplier Marchese Hospital Solutions and bulk purchaser Medbuy Corporation, along with four hospitals in Ontario and one in New Brunswick, will collectively pay $2,375,000 to settle a 2013 lawsuit stemming from the sale and administration of a premixed liquid chemotherapy medication that contained too much saline solution, according to a notice for a court hearing to approve the settlement.
Of that sum, $1,800,000 will be equally divided among the 1,202 patients, or their estates, who were given the watered-down drugs between 2012 and 2013. Another $100,000 will go to Ontario and New Brunswick provincial health insurers and the remaining $475,000 towards administration and legal fees.
As well, Marchese and MedBuy have agreed to provide the Ontario Court with affidavits “attesting to the steps they have taken to ensure the issues and concerns giving rise to the Dosing Incident have been satisfactorily addressed.”
In meeting these terms, the hospitals, Marchese and MedBuy “do not admit any wrongdoing or liability in connection with the Class Action,” the proposed settlement reads.
The class action was filed days after Cancer Care Ontario revealed in April 2013 that Windsor Regional Hospital, London Health Sciences Centre, Lakeridge Health, Peterborough Regional Health Centre and Saint John Regional Hospital had received the watered-down medication. The lawsuit originally sought $25 million in damages.
The scandal sparked outrage from patients and their families, and prompted the province to introduce regulations on drug procurement. Those new rules include a requirement that hospitals only buy drugs from licensed providers (Marchese was operating without provincial or federal oversight); the rules also grant the Ontario College of Pharmacists the power to inspect any facility where a pharmacist is employed, regardless of whether the facility is a licensed pharmacy.
However, a subsequent inquiry and report by Jake Thiessen, founding director of University of Waterloo’s School of Pharmacy, found “that there appears to be little probability that the dilution impacted cancer prognosis at all,” explained Sabrina Lombardi, a lawyer with McKenzie Lake Lawyers. The London, Ont., based law firm is one of two firms that launched the class action on behalf of the affected patients.
The inquiry also found that the mistakes made in the health-care chain did not amount to negligence.
“What this settlement represents is an acknowledgement of the added anxiety and stress that that letter letting them know about this dilution error would have put those cancer patients through,” Lombardi told the Star Thursday. “They were dealing with enough in having to undergo cancer treatment, so that’s the context that this settlement has grown from.”
Patients who want to object to the settlement or opt out of it have until Dec. 7 to do so. Lombardi said she wasn’t aware of any patients who have opted out yet.
The settlement will go through an approval hearing at a Windsor courthouse on Jan. 10, 2017.
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Retraction note: Metastatic ovarian papillary cystadenocarcinoma to the small intestine serous surface



Retraction note: Metastatic ovarian papillary cystadenocarcinoma to the small intestine serous surface: report of a case of high-grade histopathologic malignancy | Journal of Ovarian Research | Full Text

 Retraction
The co-Editors-in-Chief and Publisher have retracted this article [1] because the scientific integrity of the content cannot be guaranteed. An investigation by the Publisher found it to be one of a group of articles we have identified as showing evidence suggestive of attempts to subvert the peer review and publication system to inappropriately obtain or allocate authorship. This article showed evidence of plagiarism (most notably from the articles cited [2, 3, 4, 5, 6]) and peer review and authorship manipulation.
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OA: Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women



transheterozygosity:  two organisms that carry one mutation each, in two different genes, and selecting for the presence of both mutations simultaneously in an individual offspring.
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Full Text
 The vast majority of BRCA1 and BRCA2 mutation carriers are single heterozygotes for BRCA1 (SH1) or BRCA2 (SH2).
Table 1
Transheterozygote BRCA1 + BRCA2 mutations in 93 women (including country eg. Spain, Italy, UK, USA, Canada.....)

Abstract

Background

Most BRCA1 or BRCA2 mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both BRCA1 and BRCA2 are rare, and the consequences of transheterozygosity are poorly understood.

Methods

From 32,295 female BRCA1/2 mutation carriers, we identified 93 TH (0.3 %). “Cases” were defined as TH, and “controls” were single mutations at BRCA1 (SH1) or BRCA2 (SH2). Matched SH1 “controls” carried a BRCA1 mutation found in the TH “case”. Matched SH2 “controls” carried a BRCA2 mutation found in the TH “case”. After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2.

Results

The majority of TH (45.2 %) involved the three common Jewish mutations. TH were more likely than SH1 and SH2 women to have been ever diagnosed with breast cancer (BC; p = 0.002). TH were more likely to be diagnosed with ovarian cancer (OC) than SH2 (p = 0.017), but not SH1. Age at BC diagnosis was the same in TH vs. SH1 (p = 0.231), but was on average 4.5 years younger in TH than in SH2 (p < 0.001). BC in TH was more likely to be estrogen receptor (ER) positive (p = 0.010) or progesterone receptor (PR) positive (p = 0.013) than in SH1, but less likely to be ER positive (p < 0.001) or PR positive (p = 0.012) than SH2. Among 15 tumors from TH patients, there was no clear pattern of loss of heterozygosity (LOH) for BRCA1 or BRCA2 in either BC or OC.
                      ````````````````````````````````

Conclusions

We report evidence that the BRCA1 mutation in TH may drive these clinical TH phenotypes based on elevated OC risk in TH vs. SH2 but not SH1, and earlier age of BC diagnosis in TH vs. SH2 but not SH1. Therefore, TH may be managed more like BRCA1 mutation carriers than BRCA2 mutation carriers. In contrast, TH breast tumor characteristics (e.g., ER/PR status) are intermediate in phenotype to SH1 and SH2. Future studies are warranted to understand whether TH should be managed differently to SH1 or SH2 carriers, and, if so, to enable individualized counseling and clinical management appropriate for TH mutation carriers.

 
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Genetic variants in telomere-maintenance genes are associated with ovarian cancer risk and outcome



 Telomeres are an essential part of human cells that affect how our cells age. 1,2. Telomeres are the caps at the end of each strand of DNA that protect our chromosomes, like the plastic tips at the end of shoelaces. 3.
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open access

 Most ovarian cancer patients present at an advanced stage with poor prognosis. Telomeres play a critical role in protecting chromosomes stability. The associations of genetic variants in telomere maintenance genes and ovarian cancer risk and outcome are unclear. We genotyped 137 single nucleotide polymorphisms (SNPs) in telomere-maintenance genes in 417 ovarian cancer cases and 417 matched healthy controls to evaluate their associations with cancer risk, survival and therapeutic response. False discovery rate Q-value was calculated to account for multiple testing. Eleven SNPs from two genes showed nominally significant associations with the risks of ovarian cancer. The most significant SNP was TEP1: rs2228026 with participants carrying at least one variant allele exhibiting a 3.28-fold (95% CI: 1.72-6.29; P < 0.001, Q = 0.028) increased ovarian cancer risk, which remained significant after multiple testing adjusting. There was also suggested evidence for the associations of SNPs with outcome, although none of the associations had a Q < 0.05. Seven SNPs from two genes showed associations with ovarian cancer survival (P < 0.05). The strongest association was found in TNKS gene (rs10093972, hazard ratio = 1.88; 95% CI: 1.20-2.92; P = 0.006, Q = 0.076). Five SNPs from four genes showed suggestive associations with therapeutic response (P < 0.05). In a survival tree analysis, TEP1:rs10143407 was the primary factor contributing to overall survival. Unfavourable genotype analysis showed a cumulative effect of significant SNPs on ovarian cancer risk, survival and therapeutic response. Genetic variations in telomere-maintenance genes may be associated with ovarian cancer risk and outcome.

Study population

Patients (n = 417) with pathologically confirmed ovarian cancer were recruited from the University of Texas MD Anderson Cancer Center from 1998 to 2011. All case participants were newly diagnosed, histologically confirmed ovarian cancer and previously untreated before enrolment. There were no age, ethnicity or cancer stage restrictions on recruitment. Healthy control participants (n = 417) were recruited from Kelsey-Seybold Clinic, a large multi-specialty physician group in Houston metropolitan area. Controls without cancer history other than non-melanoma skin cancer were recruited during the same time period as the cases, and were matched to cases on age (±5 year) and ethnicity......... Epidemiologic data including demographics, tobacco use history, bw and height, history of cancer, and medical history were collected for all cases and controls. Information on vital status was obtained from the medical records and the Social Security Death Index. For each participant, a blood sample was drawn into coded heparinized tubes for lymphocyte isolation and DNA extraction.

In summary, this study provides epidemiologic evidence for the associations of telomere-maintenance gene variations with ovarian cancer risk and clinical outcome. Future studies are warranted to validate our findings and explore the biological mechanisms underlying the association of telomere maintenance gene variants with ovarian cancer risks and outcome.

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OA: Response to sunitinib (Sutent) in chemotherapy refractory clear cell ovarian cancer



open access: Gynecologic Oncology Reports
 

1.1. Case description

A 59 year old patient was discussed at the gynaecologic oncology multi-disciplinary meeting having presented with abdominal distension with radiological features of an ovarian malignancy. A CT scan demonstrated a complex 16 cm × 13 cm mass arising in the pelvis from the right ovary. Her baseline serum tumour marker ca125 was 34 U/ml She had no medical history of note and was previously fit and well. Her ECOG performance status was 1. There was no family history of malignancy.....

Highlights

  • •
    Case describes a response to sunitinib in clear cell ovarian cancer.
  • •
    Discussion of unique molecular characteristics of clear cell ovarian cancers
  • •
    Practical points regarding dosing and toxicity when using sunitinib discussed


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Will unanticipated genetic mutations lead to subsequent disease?



Science news

 ....Eventually, using an individual's genomic variants to predict and prevent future illness may become a routine part of health care. However, it remains to be seen whether identifying individuals with genetic mutations will result in sufficient clinical benefit to merit the risks and costs of downstream imaging studies or procedures. The authors caution that this study does not provide evidence that recognizing genetic mutations directly confers medical benefit. In seeking to explore the related question of clinical outcomes, Green and his team have also implemented a separate randomized clinical trial of medical sequencing called the MedSeq Project, and have organized a Consortium to track medical outcomes among any ostensibly healthy individuals who have been sequenced for predictive purposes.

Journal Reference:
  1. P. Natarajan, N. B. Gold, A. G. Bick, H. McLaughlin, P. Kraft, H. L. Rehm, G. M. Peloso, J. G. Wilson, A. Correa, J. G. Seidman, C. E. Seidman, S. Kathiresan, R. C. Green. Aggregate penetrance of genomic variants for actionable disorders in European and African Americans. Science Translational Medicine, 2016; 8 (364): 364ra151 DOI: 10.1126/scitranslmed.aag2367
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