Update on olaparib in ovarian cancer (Prof Ledermann - video)

YouTube

Published on Aug 2, 2016

Prof Ledermann talks to ecancertv at ASCO 2016 about the updated survival data associated with the PARP inhibitor olaparib in a certain subset of ovarian cancer patients.

He also highlights the novel exploratory endpoints that were used for the first time within an oncology trial (TFST and TSST), and highlights that 15% of patients entered into the study possessing mutant strains of BRCA are still receiving maintenance therapy 5 years later.

For future clinical use, it is important to establish precisely those patients who will benefit the most, due to the cost of the drug.

• Category

  • Science & Technology

Dr. Robert Coleman on the Importance of BRCA Testing in Ovarian Cancer

YouTube (2:21 min)

Excess Weight Tied to Higher Risk for Many Cancers (another 'not so fast')

MedNews

Dr. Clifford Hudis, chief executive officer of the American Society of Clinical Oncology, reacted to the findings with caution, stressing that "cause and effect is not proven."
He added that it's premature to conclude that "obesity is the cause of any individual's cancer."

 The study (requires subscription) was published Aug. 25 in the The New England Journal of Medicine. It was funded in part by the American Cancer Society and the U.S. Centers for Disease Control and Prevention.

Analysis of Founder Mutations in Rare Tumors Associated With HBOC Reveals a Novel Association of BRCA2 Mutations + Ampulla of Vater Carcinomas

Open access:
 Analysis of Founder Mutations in Rare Tumors Associated With Hereditary Breast/Ovarian Cancer Reveals a Novel Association of BRCA2 Mutations with Ampulla of Vater Carcinomas

 ....BRCA2 mutations were observed with a frequency of 14.3% in ampulla of Vater carcinomas. In conclusion, taking into account the implications for both the individuals and their family members, we recommend that patients with these neoplasias should be offered BRCA1/BRCA2 genetic testing and we here show that it is feasible to test for founder mutations in archival tumor tissue. Furthermore, we identified for the first time a high frequency of germline BRCA2 mutations in ampullary cancers.

Update on Study 19 trial of olaparib in serous ovarian cancer (video)

video (2:39 min)
 Posted on : 08/17/16

 Description: Jonathan Ledermann, MD, FRCP from University College London, London, UK discusses his presentation on the update on the results of the Study 19 trial (NCT00753545). Study 19 was a randomized maintenance trial using olaparib in patients with recurrent high grade serous ovarian cancer, who had previously responded to platinum-based chemotherapy. Patients were randomized to olaparib or a placebo. Prof. Ledermann talks about the 3 year follow-up on overall surviva (OS) and how there was meaningful improvement in patients taking olaparib. These findings, however, were not statistically significant. Prof. Ledermann further discusses how the trial looked into several supplementary exploratory endpoints to support the clinical value of the difference in OS of 4.7 months that was found. Endpoints looked at were: time to first subsequent treatment and time to second subsequent treatment. Prof. Ledermann discusses the importance of olaparib to OS rates. Recorded at the American Society of Oncology (ASCO) 2016 Annual Meeting held in Chicago, IL.

#HealthTO looks at the future of privacy in the digital healthcare space

BetaKit

 “What I find disturbing is that the conversation and dialogue around privacy has been very much focused on the process and the security itself instead of how we use the data,” said Soyao. “We’re missing the point because instead of talking about regulation, the point we need to address is how we use the data to make better care for patients?”

#HealthTO

Challenge of Prognostic Uncertainty in the Modern Era of Cancer Therapeutics

open access

Hyperthermic intraperitoneal chemotherapy with paclitaxel or cisplatin in patients with stage III-C/IV ovarian cancer. Is there any difference?

 Cytostatic is a word some doctors and researchers use to describe the way some anti cancer drugs work.
                        ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
abstract:
Hyperthermic intraperitoneal chemotherapy with paclitaxel or cisplatin in patients with stage III-C/IV ovarian cancer. Is there any difference?
 

Highlights

•

There is a benefit of HIPEC treatment compared with cytoreduction alone.

•

Incomplete cytoreduction and high PCI reduced disease-free survival.

•

Type of cystotatic is not relevant regarding disease free survival analysis.

---

Abstract

Objective

To compare the results of the administration of HIPEC with Paclitaxel or Cisplatin after cytoreduction in patients with stage IIIC-IV ovarian cancer, especially focused on disease-free survival.

Patients

We retrospectively analyzed a consecutive series of patients operated after being diagnosed with stage III-C/IV serous epithelial ovarian carcinoma. Patients included in the study were treated between January 2008 and March 2015. After cytoreduction, Paclitaxel (doses of 60 mg/m²O or Cisplatin (doses of 75 mg/m²) were used.

Results

A total of 111 patients were included. Median age was 61 years. In 60 of them (54%) Paclitaxel was used during HIPEC treatment and 51 patients (46%) were treated with Cisplatin. PCI was similar between groups (PCI = 11 in both cases). Median follow up was 34 months (12–96 months). The median disease free survival in Paclitaxel Group was 27 months and 33 months in Cisplatin Group (p = 0.551). In patients treated with Paclitaxel disease free survival rates at 1, 2, and 3 years were 79%, 60% and 46%. In patients treated with Cisplatin disease free survival at 1, 2, and 3 years were 64%, 50% and 40% respectively. After a multivariate analysis, incomplete cytoreduction and PCI >11  were identified as independent factors associated with a reduced disease-free survival. Cystotatic used was not relevant regarding disease free survival analysis.

Conclusion

HIPEC with paclitaxel or cisplatin after cytoreduction in patients with ovarian cancer IIIC-IV has not shown different results in disease-free survival outcomes.

When a (ovarian cancer) Patient Becomes a Friend, How Do You Say Goodbye? | ASCO Connection

ASCO Connection

Cholesterol Testing: Is Fasting Necessary? (Europe/U.S.)

labtestsonline

Not Enough Female Urologists to Meet Growing Patient Demand

medical news

FDA grants priority review to rucaparib for advanced BRCA –mutated ovarian cancer (see notes)

medical news:
FDA grants priority review to rucaparib for advanced BRCA –mutated ovarian cancer

 The ARIEL clinical development program evaluated rucaparib in women with advanced ovarian cancer.

Noteworth
  Aug 23 2016
 

FDA to review Clovis' rucaparib NDA for ovarian cancer, action date in six months; shares jump 31%

Aug 23 2016, 15:52 ET | About: Clovis Oncology (CLVS) | By: Douglas W. House, SA News Editor

Battered and bruised Clovis Oncology (CLVS +31%) recaptures some its former glory on the news that the FDA has accepted for review its New Drug Application (NDA) seeking approval of Breakthrough Therapy-tagged rucaparib for the treatment of advanced ovarian cancer in patients with BRCA-mutated tumors inclusive of both germline and somatic BRCA mutations and who have been treated with least two chemo regimens.

The NDA has Priority Review status which shortens the review clock to six months from the usual 10 months. The agency's action date (PDUFA) is February 23, 2017.

In two late-stage studies, the overall objective response rate for rucaparib-treated ovarian cancer patients was 54% (n=57/106).

Rucaparib is a small molecule poly ADP-ribose polymerase (PARP) inhibitor that specifically binds to PARP-1 and PARP-2. PARPs are proteins that play a key role in repairing single-strand breaks in DNA. By inhibiting their action, multiple DNA breaks form during the replication process in tumor cells that have the BRCA1, BRCA2 or PALB2 mutation which leads to cell death.

Clovis had lost ~90% of its value since late 2015 when it stumbled with rociletinib. Shares have rebounded of late.  They are up more than 113% since bottoming at $11.57 on June 27.

PARP inhibitor competitor TESARO (TSRO -5.9%) slumps on the news.

author's response: Comments on 'The incidence of leukaemia in women with BRCA1/BRCA2 mutations

#3: author response
British Journal of Cancer - Response to /`Comments on 'The incidence of leukaemia in women with BRCA1 and BRCA2 mutations: an International Prospective Cohort Study/'/'
 

Sir,

We thank Paradiso et al. from Bari for examining the Italian data base for correlation with the reported incidence of leukaemia in the families with BRCA1 and BRCA2 mutations. These authors did not take into account a past history of breast cancer or the use of cytotoxic chemotherapies in the analysis, but overall the results lend support to our conclusion that the risk of leukaemia in mutation carriers is likely to be low, if raised at all (Iqbal et al, 2016).

Friedenson provides a comprehensive description of the many studies that tie breast cancer susceptibility genes with propensity to leukaemia, with an emphasis on immunity and viral carcinogenesis. Little is specific to the risk in BRCA carriers. He has some concerns that our methods may have obscured a significant underlying association between BRCA gene mutations and leukaemia—we have used the same methodology to elaborate cancer risks for carriers for a range of sites, including pancreas, colon, breast and ovary. We now accept that there might be a small iatrogenic risk of leukaemia associated with chemotherapy for breast cancer in BRCA carriers, but we have also found that chemotherapy is a highly effective treatment for these patients (Narod et al, 2013; Metcalfe et al, 2015) and we cannot identify women at sufficiently high risk of leukaemia or sufficiently low risk of death from breast cancer that they might forego chemotherapy.

(#2) Comment on: The incidence of leukaemia in women with BRCA1/BRCA2 mutations

2nd article:
Comment on /`The incidence of leukaemia in women with BRCA1 and BRCA2 mutations: an International Prospective Cohort Study/'

Comment on: The incidence of leukaemia in women with BRCA1 and BRCA2 mutations

open access:
Comment on /`The incidence of leukaemia in women with BRCA1 and BRCA2 mutations: an International Prospective Cohort Study/'

CXCL9 and CXCL10 predict survival and are regulated by cyclooxygenase inhibition in advanced serous ovarian cancer

open access:
CXCL9 and CXCL10 predict survival and are regulated by cyclooxygenase inhibition in advanced serous ovarian cancer

 In conclusion, we demonstrated for the first time that the two CXCR3-binding chemokines CXCL9 and CXCL10 are independent predictors of an improved OS in HGSC. Furthermore, we identified the COX system as a suitable pharmacologic target to augment intratumoral chemokine concentrations. On the basis of our results, the addition of indomethacin, rather than celecoxib, to immunotherapies in future clinical trials should be explored, with the goal to improve their efficacy by enhancing the tumour-suppressive lymphocytic infiltration in ovarian cancer.

Sustaining hope and life courage in patients undergoing ovarian cancer surgery – the impact of care

abstract:
Sustaining hope and life courage in patients undergoing ovarian cancer surgery – the impact of care

 Ovarian cancer is the leading cause of death from a gynaecological malignancy in the Western World. To explore if experiences of physical comfort influenced hope and life courage during final diagnosis and early treatment, qualitative research interviews were performed with women undergoing surgery for ovarian cancer. By applying a phenomenological-hermeneutic methodology, the findings were systematically identified, put into meaning-structures, interpreted and critically discussed. The empirical material constituted a main theme concerning “Hope and life courage are created in the interplay between body and mind,” where findings dealt with personal reflections and experiences in relation to the subthemes: “Experiencing discomfort,” “The impact of care” and “Comfort and hope.” The women's general health condition became impacted not only by their ovarian cancer disease but also by the treatment, and it was a main finding that sufficient symptom management combined with sensitive attention of the patient sustained her hope, life courage and action competences. Surgery constitutes an essential part of sufficient cancer treatment. However, the diagnostic and pre-operative phase represents an insufficiently investigated area in cancer care. Improvements are therefore vital to reduce the disease burden, and improve patients' general health and quality of life, during and after treatment.

Dermatological adverse events with taxane chemotherapy

abstract
 

Taxanes (docetaxel and paclitaxel) are among the most commonly prescribed anticancer drugs approved for the treatment of metastatic or locally advanced breast, non-small cell lung, prostate, gastric, head and neck, and ovarian cancers, as well as in the adjuvant setting for operable node-positive breast cancers. Although the true incidence of dermatological adverse events (AEs) in patients receiving taxanes is not known, and has never been prospectively analysed, they clearly represent one of the major AEs associated with these agents. With an increase in the occurrence of cutaneous AEs during treatment with novel targeted and immunological therapies when used in combination with taxanes, a thorough understanding of reactions attributable to this class is imperative. Moreover, identification and management of dermatological AEs is critical for maintaining the quality of life in cancer patients and for minimizing dose modifications of their antineoplastic regimen. This analysis represents a systematic review of the dermatological conditions reported with the use of these drugs, complemented by experience at comprehensive cancer centres. The conditions reported herein include skin, hair, and nail toxicities. Lastly, we describe the dermatological data available for the new, recently FDA-and EMA- approved, solvent-free nab-paclitaxel.

KEYWORDS:

docetaxel; hair; nab-paclitaxel; nail; paclitaxel; skin; taxanes; toxicity

Genetically Predicted Body Mass Index and Breast Cancer Risk: European Descent

open access:
Genetically Predicted Body Mass Index and Breast Cancer Risk: Mendelian Randomization Analyses of Data from 145,000 Women of European Descent

What Do These Findings Mean?

• Our results from postmenopausal women contradict prior findings from population studies, which used measured, rather than genetically predicted, BMI.
• BMI predicted using genetic variants identified to date may be more closely related to body weight in early life or midlife, which is negatively associated with risk of breast cancer. Measured high BMI later in life may be influenced by environmental factors that are associated with increased risk of breast cancer.
• More research is needed on the interrelationship of genetic factors, environment, and BMI in the risk of breast cancer.

Prevalence of Appendiceal Lesions in Appendicectomies Performed During Surgery for Mucinous Ovarian Tumors

abstract
 Prevalence of Appendiceal Lesions in Appendicectomies Performed During Surgery for Mucinous Ovarian Tumors: A Retrospective Study

Objectives: The aim of this study was to assess the frequency of appendiceal pathology in women undergoing surgery for mucinous ovarian neoplasm and to evaluate whether appendicectomy is necessary.

Methods: This single-institution retrospective study reviewed prevalence of appendiceal lesions in all patients operated on at our institution from 2002 to 2013 with the final diagnosis of mucinous tumor of the ovary. Clinicopathological data were analyzed.

Results: One hundred twenty-three cases were identified. These included 45 (37%) benign mucinous ovarian neoplasms, 63 (51%) borderline, and 11 (9%) invasive mucinous ovarian tumors. In addition, 4 (3%) cases of metastatic tumors to the ovary were also identified. Appendiceal pathology was found in association with all types of mucinous ovarian tumors (benign, borderline, and malignant). In 24% of cases, appendix was macroscopically abnormal at the time of the surgery, prompting the surgical removal. Regardless of the gross findings, microscopic abnormality in the appendix was seen in 24% of all cases. The prevalence of significant occult microscopic appendiceal pathology, that is, when the appendix was grossly normal, was 6%.

Conclusions: Given the prevalence of coexisting appendiceal pathology found in this study and the reported low rates of complications associated with the procedure, an appendicectomy is recommended in the management of all mucinous ovarian neoplasms.

Use of implicit persuasion in decision making about adjuvant cancer treatment: A potential barrier to shared decision making

abstract:
Use of implicit persuasion in decision making about adjuvant cancer treatment: A potential barrier to shared decision making

Highlights

Section 1: What is already known on this subject.

•

Shared decision-making (SDM) is widely advocated, especially when there is no obvious best treatment option.

•

A prerequisite of SDM is treatment information provision without implicit value judgements, i.e., implicit persuasion.

•

There is no evidence on whether implicitly persuasive behaviours are used in oncological practice, and if so, which.

Section 2: What this study adds.

•

Implicit persuasion is frequently used, irrespective of expected treatment benefit, and is associated with a greater likelihood of reaching a decision.

•

Clinicians must realize that the use of implicit persuasion can subvert their intent to share decisions with patients.

Changing patterns of referrals and outcomes of genetic participation in gynaecological-oncology multidisciplinary care

abstract
 

Background

Genetic participation in gynaecological oncology multidisciplinary team meetings (MDT) may identify the sentinel cancer in women with hereditary breast-ovarian cancer syndrome or Lynch syndrome.

Aims

To identify the changing patterns of genetic referral from 2010 to 2014 and the outcomes of referrals through clinical MDT case review.

Materials and Methods

Medical records of cases of gynaecological cancer presented at the MDT meetings and genetics databases were reviewed to determine the frequency and outcomes of recommendations for genetic referral between 2010 and 2014.

Results

Four hundred and sixty-two women of 2523 cases reviewed were recommended for referral, increasing from 8% in 2010 to 25% in 2014. However, 167 of 462 patients (36%) had not registered with a Hereditary Cancer Clinic in NSW/ACT, including 11 women with high-grade serous ovarian cancer and seven women with abnormal MMR immunohistochemistry. Mutations were identified in 40 of 165 women (24%) undergoing breast cancer BRCA1/2 testing and in ten of 25 women (40%) who underwent MMR genetic testing. Eighty-one first- or second-degree relatives of these women have undergone predictive testing, identifying 48 mutation carriers and 33 non-carriers.

Conclusion

Changing indications and increased participation by a genetic consultant in the weekly MDT meeting has led to increasing genetic referrals over the last five years. Follow up of referrals needs to be addressed. With decreasing costs of genetic testing and use of readily transportable DNA collected through saliva or mouth swabs, we propose that distance should not be a barrier to this model being extended to all centres providing care to gynaecological cancer patients.

Challenging Roadblocks to Cancer Cure

open access - pdf

Abstract

The Pezcoller Symposium in Trento, Italy, June 2015, focused entirely on the question of why advanced cancer cure is so uncommon despite the extraordinarily rapid growth of invaluable therapeutic information. Participants were asked to define and to critically evaluate real and potential obstacles to permanent disease eradication. High-level concepts on potential road blocks to cures as well as opportunities for intervention in diverse areas of investigation ranging from genomic alterations to metabolism, microenvironment, immunity, and mechanotransduction were discussed. Provocative concepts and novel therapeutic avenues were proposed. What follows is a critical analysis of the highlights of this meeting.  

Cancer Res; 76(17); 1–7. ©2016 AACR.

Finally, knowing in detail what molecular capabilities manifested
by a patient's tumor have the potential to promote future
clinical lethality may, when suitably impeded, prove important to
converting remissions or stable disease into long-term survival.

Newsroom : Statement from (Ontario) Minister of Health on Canadian Institute for Health Information Report

Newsroom : Statement from Minister of Health on Canadian Institute for Health Information Report

Statement from Minister of Health on Canadian Institute for Health Information Report

August 23, 2016 10:45 A.M.

Ministry of Health and Long-Term Care

Today, Dr. Eric Hoskins, Ontario's Minister of Health and Long-Term Care, issued the following statement:
"I want to thank the Canadian Institute for Health Information (CIHI) for their report on physicians in Canada. Their report confirms what we've said for months - that Ontario's physicians remain among the highest paid in Canada, earning more than $25,000 above the national average. On average, Ontario doctors' gross billings are approximately $364,000 per year. That figure is only $2,000 -- or half of one per cent -- less than the highest paid doctors in Canada.
It is also important to note that CIHI's analysis does not include radiologists, one of our highest-paid specialties. Last year in Ontario, more than 150 radiologists billed over $1 million.  In total, $1.5 billion worth of physician payments are not included in these calculations.
This report confirms that, contrary to the claims of some, Ontario's doctors remain well paid. Our government is determined to strike a fair balance that will keep our physicians among the best paid in the country, while ensuring that we have the ability to continue to invest in other critical areas of our health care system, such as home and community care, our hospitals, nurses and personal support workers."

CMAGC twitter post - re: patients as owners of records

twitter - #Pamela Fayerman

Why prescription drugs cost twice as much in U.S. versus other advanced nations ― and what might be done about it

Why prescription drugs cost twice as much in U.S. versus other advanced nations ― and what might be done about it

Exploring the link between chemotherapy-induced toxicities - video 1:19 min

oncologytube

 Description: Rachel Gibson, PhD of University of South Australia, Adelaide, Australia explores the links between chemotherapy induced toxicities that would normally be treated in isolation. With chemotherapy induced diarrhea, many patients are experiencing significant pain. Dr. Gibson mentions studies which have explored this further in the brain, in the case of chemotherapy induced neuropathy. Results from studies show that pathogenic bacteria responsible for producing LPS are also found in the spinal cord. Therefore, there is hope to show that in the spinal cord there are two linked toxicities. This would be the first time showing clear mechanistic links between toxicities and would be a huge step forward for patients in supportive care. Recorded at the Multinational Association of Supportive Care in Cancer (MASCC) 2016 Annual Congress in Adelaide, Australia.

Health Workforce | Canadian Institute for Health Information (eg. genetic counsellors, physicians, physician assistants...)

CIHI
  
Health Workforce

Individuals delivering care or working in health human resources (HHR) are one of the greatest assets of our health care system. Evidence-based planning and management of HHR is a vital part of making sure Canadians can access health services when and where they need them.
Data is submitted to CIHI by national professional societies and associations, provincial/ territorial regulatory bodies and governments, and educational institutions.
CIHI's Health Workforce Database includes information about the 30 groups of health care professionals listed below—information such as practice setting, regulatory environment, supply, and demographic, education and employment characteristics. This information is used by health care planners, decision-makers, policy-makers and researchers to support resource and use planning.

• Audiologists
• Chiropractors
• Dental assistants
• Dental hygienists
• Dentists
• Dietitians
• Environmental public health professionals
• Genetic counsellors
• Health information management professionals
• Licensed practical nurses
• Medical laboratory technologists
• Medical physicists
• Medical radiation technologists
• Midwives

• Occupational therapists
• Opticians
• Optometrists
• Paramedics
• Pharmacists
• Pharmacy technicians
• Physicians
• Physician assistants
• Physiotherapists
• Psychologists
• Registered nurses/nurse practitioners
• Registered psychiatric nurses
• Respiratory therapists
• Social workers
• Speech–language pathologists

We welcome your feedback and questions. Email us at hhr@cihi.ca

Related Content

Publications

• Medical Radiation Technologists, 2014
• Medical Laboratory Technologists, 2014
• Occupational Therapists, 2014 
• Pharmacists, 2014

• Physiotherapists, 2014
• Physicians in Canada, 2014 
• Regulated Nurses, 2015
• Canada's Health Care Providers: Provincial Profiles, 2013

2015 Report: Physicians in Canada (CIHI) eg. #'s, GROSS income .....(updated)