OA: Genome‑wide analysis of gynecologic cancer: The Cancer Genome Atlas in ovarian and endometrial cancer (Review)

(Review)
  (click on pdf for full view)
 

Cancer typically develops due to genetic abnormalities, but a single gene abnormality cannot completely account for the onset of cancer. The Cancer Genome Atlas (CGA) project was conducted for the cross‑sectional genome‑wide analysis of numerous genetic abnormalities in various types of cancer. This approach has facilitated the identification of novel AT‑rich interaction domain 1A gene mutations in ovarian clear cell carcinoma, frequent tumor protein 53 (TP53) gene mutations in high‑grade ovarian serous carcinoma, and Kirsten rat sarcoma and B‑rapidly accelerated fibrosarcoma proto‑oncogene, serine/threonine kinase gene mutations in low‑grade ovarian serous carcinoma. Genome‑wide analysis of endometrial cancers has led to the establishment of four subgroups: Polymerase ultramutated, microsatellite instability hypermutated, genome copy‑number low and genome copy‑number high. These results may facilitate the improvement of the prediction of patient prognosis and therapeutic sensitivity in various types of gynecologic cancer. The enhanced use of currently available therapeutic agents and the development of novel drugs may be facilitated by the novel classification of ovarian cancer based on TP53 mutations, the efficacy of poly (ADP‑ribose) polymerase inhibitors for tumors with breast cancer 1/2 mutations and the effect of phosphoinositide‑3‑kinase (PI3K)/mammalian target of rapamycin inhibitors for tumors with mutations in the PI3K/protein kinase B signaling pathway. Important results have been revealed by genome‑wide analyses; however, the pathogenic underlying mechanisms of gynecologic cancer will require further studies and multilateral evaluation using epigenetic, transcriptomic and proteomic analyses, in addition to genomic analysis.

Related Articles

• ARID1A gene mutation in ovarian and endometrial cancers (Review)
• Amplification of the bromodomain-containing protein 4 gene in ovarian high‑grade serous carcinoma is associated with worse prognosis and survival
• Aurora kinase inhibitors: Potential molecular‑targeted drugs for gynecologic malignant tumors (Review)
• Improved survival associated with somatic PIK3CA mutations in copy‑number low endometrioid endometrial adenocarcinoma
• TP53 oncomorphic mutations predict resistance to platinum‑ and taxane‑based standard chemotherapy in patients diagnosed with advanced serous ovarian carcinoma

Hereditary Ovarian Cancer and Risk Reduction

abstract

  Available online 17 January 2017

 

Purchase $35.95

Highlights

•

14% of epithelial ovarian cancer is due to mutations in BRCA1 or BRCA2.

•

The risk of ovarian cancer in a BRCA1/2 mutation carrier is 18-40%.

•

Screening for ovarian cancer is not proven to improve outcome.

•

Women at high risk are recommended risk-reducing salpingo-oophorectomy around age 40.

•

Careful examination of the specimen is required for occult malignancy requiring treatment.

•

Panel genetic testing is available but results of genes without clear management guidelines or variants of uncertain significance should be interpreted with caution.

---

Mutations in BRCA1 and BRCA2 account for the majority of families with hereditary breast and ovarian cancer syndrome, and account for 14% of epithelial ovarian cancer. Despite next generation sequencing, other identified genes (Lynch Syndrome, RAD51C, RAD51D and BRIP1) account for only a small proportion of cases. The risk of ovarian cancer by age 70 is around 40% for BRCA1 and 18% for BRCA2. Most of these cancers are high grade serous cancers which predominantly arise in the fimbriae of the fallopian tube. Ovarian screening does not improve outcome, so women at high risk are recommended to undergo risk-reducing salpingo-oophorectomy around the age of 40, followed by HRT. Specimens should be carefully examined for occult malignancy. Mutation carriers may benefit from newly developed PARP inhibitors. Genetic testing should only be done after careful counseling, particularly if testing involves testing of panels of genes which may identify unsuspected disease pre-disposition or confusing variants of uncertain significance.

Who will keep predatory science journals at bay now that Jeffrey Beall's blog is gone?

opinion

OA: Tracking the origin of simultaneous endometrial and ovarian cancer by next-generation sequencing – a case report

BMC Cancer 

 The simultaneous occurrence of an endometrial and ovarian carcinoma in women below 50 years of age is a common combination [3], however, the pattern of pulmonary metastasis in this low grade and low stage cancer disease is unusual.

 The early onset of the malignant disease in this young woman at age 33 suggests possible germline mutations that accelerated the accumulation of genetic aberrations promoting cancer development. A common genetic defect that leads to the development of endometrial cancer in the context of Lynch syndrome is aberrations in the mismatch repair (MMR) proteins. Interestingly, neither mutations in the MMR genes nor increased double strand breaks could be detected.

Abstract

Background

Endometrioid adenocarcinoma of the uterus and ovarian endometrioid carcinoma share many morphological and molecular features. Differentiation between simultaneous primary carcinomas and ovarian metastases of an endometrial cancer may be very challenging but is essential for prognostic and therapeutic considerations.

Case Presentation

In the present case study of a 33 year-old patient we used targeted amplicon next-generation re-sequencing for clarifying the origin of synchronous endometrioid cancer of the corpus uteri and the left ovary. The patient developed a metachronous lung metastasis of an endometrioid adenocarcinoma four years after hyster- and adnexectomy, vaginal brachytherapy and treatment with the synthetic steroid tibolone. Removal of the metastasis and megestrol treatment for seven years led to a complete remission......

FDA Begins Cancer Product Review Center (note: comment ovarian cancer)

science news
  January 20th, 2017

The Oncology Center of Excellence aims to better coordinate evaluations of new therapeutic products for cancer by the FDA’s separate offices for drugs, biologics, and medical devices. While applications and review criteria for new treatments and devices are not expected to change, FDA says the new center plans to draw more on the expertise of scientific and regulatory professionals in these offices, where needed, and encourage more collaboration across the usual hierarchies.

In an agency blog post after his appointment in June, Pazdur noted the oncology center will emulate models from cancer care facilities and the academic world that put more emphasis on multi-disciplinary collaboration to confront the complexities of cancer. The new center also intends to encourage more patients’ perspectives in FDA’s regulatory decision making, an idea that became a personal mission after his wife Mary died from ovarian cancer in November 2015.

Cancer Risk in Women Treated with Fertility Drugs According to Parity status

abstract
Cancer Risk in Women Treated with Fertility Drugs According to Parity status - A Registry-based Cohort Study. | Cancer Epidemiology, Biomarkers

Background Long-term safety of assisted reproductive techniques (ART) is of interest as use is increasing. Cancer risk is known to be affected by parity. This study examined risk of cancer after fertility treatment, stratified by women's parity. Methods Data was obtained on all women (n=1 353 724) born in Norway between 1960-1996. Drug exposure data (2004-2014) was obtained from the Norwegian Prescription Database [drugs used in ART and clomiphene citrate (CC)]. The Medical Birth Registry of Norway provided parity status. Hazard ratios were calculated for all site cancer, breast, cervical, endometrial, ovarian, colorectal, central nervous system, thyroid cancer and malignant melanoma.
Results In 12 354 392 person-years of follow-up, 20 128 women were diagnosed with cancer. All-site cancer risk was (1.14) and (1.10) following CC and ART exposure respectively. For ovarian cancer, a stronger association was observed for both exposures in nulliparous (HR 2.49 and HR 1.62) versus parous women (HR 1.37 and HR 0.87). Elevated risk of endometrial cancers was observed for CC exposure in nulliparous women (4.59 vs. 1.44). Risk was elevated for breast cancer in parous women exposed to CC (1.26) and among nulliparous women after ART treatment (2.19).
Conclusion CC appears associated with increased risk of ovarian and endometrial cancer. Elevations in risks of breast and thyroid cancer were less consistent across type of drug exposure and parity.
Impact Continued monitoring of fertility treatments is warranted.

Patient Perspective @ ECCO2017 - Patient Advocacy

Patient Advocacy

OA: Characterizing the Nature of Scan Results Discussions: Insights Into Why Patients Misunderstand Their Prognosis

Characterizing the Nature of Scan Results Discussions: Insights Into Why Patients Misunderstand Their Prognosis: Journal of Oncology Practice

"ovarian" Searchable Programme for ECCO 2017

Searchable Programme for ECCO 2017

(snapshot)
 

ECCO 2017 Scientific Programme

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Browse and search the ONLINE PROGRAMME to find the latest sessions and lectures you are interested in. This online tool helps you search for your favourite topic or find world leading speakers taking part in European Cancer Congress enabling you achieve the very best from your congress participation.

Recurrent ovarian Sertoli–Leydig cell tumor in a child with Peutz–Jeghers syndrome

abstract

 We present a female child with Peutz–Jeghers syndrome (PJS) with a recurrent ovarian Sertoli–Leydig cell tumor (SLCT). SLCTs are relatively rare sex cord neoplasms that can occur in PJS. The patient was an African-American female who first presented at the age of 3 years with precocious puberty, and then at the age of 17 years with abdominal pain and irregular menses. In each case, she had resection of the mass, which included oophorectomy. To our knowledge, this is the first reported case in a child with PJS to have a recurrent ovarian SLCT.

Emesis and nausea related to single agent trabectedin (Yondelis) in ovarian cancer patients

abstract:
Emesis and nausea related to single agent trabectedin in ovarian cancer patients: a sub-study of the MITO15 project

 The MITO 15 was a prospective, single-arm trial, evaluating trabectedin monotherapy in patients with recurrent ovarian cancer (OC) who were BRCA mutation-carriers or had a BRCAness phenotype. It is largely reported that trabectedin may induce nausea and vomiting but the real emetogenic potential of the drug, in the different schedules, has never been fully described; furthermore, OC patients are known to have an enhanced risk of developing nausea and vomiting due to female gender, abdominal spreading of the disease, and major surgery experienced by most of them. We thought to carry on a sub-study in the MITO 15 context focused on chemotherapy-induced nausea and vomiting (CINV) associated with trabectedin single agent. For all patients enrolled in the trial, we evaluated the antiemetic regimen at the first cycle, acute and delayed CINV, any rescue therapy, any change in the prophylactic antiemetic regimen, and the potential relationship between dexamethasone dosage and incidence of CINV. Overall, our findings were consistent with literature and confirmed that trabectedin can be classified as moderately emetogenic. We observed slightly higher rates of both nausea and vomiting compared to previous experiences with trabectedin monotherapy, probably due to intrinsic features of our population: all females and suffering from ovarian cancer. It seems that in preventing acute CINV, the combination of three drugs was more effective than the doublet; however, the difference did not reach statistical significance; further studies are required to verify such hypothesis. Given the extreme heterogeneity of the antiemetic regimens used, it appears that a standard antiemetic protocol does not exist and more specific guidelines for clinicians are needed.

Key messages for communicating information about BRCA1/2 to women with breast or ovarian cancer

abstract:
Key messages for communicating information about BRCA1 and BRCA2 to women with breast or ovarian cancer: consensus across health professionals and service users - Jacobs - Psycho-Oncology
 

Objectives

Genetic testing of cancer predisposing genes will increasingly be needed in oncology clinics in order to target cancer treatment. This Delphi study aimed to identify areas of agreement and disagreement between genetics and oncology health professionals and service users about the key messages required by women with breast/ovarian cancer who undergo BRCA1/BRCA2 genetic testing and the optimal timing of communicating key messages.

Methods

Participants were 16 expert health professionals specialising in oncology/genetics and 16 service users with breast/ovarian cancer and a pathogenic BRCA1/BRCA2 variant. On-line questionnaires containing 53 inductively developed information messages were circulated to the groups separately. Participants rated each message as key/ not key on a Likert scale and suggested additional messages. Questionnaires were modified according to the feedback and up to three rounds were circulated. Consensus was reached when there was ≥75% agreement.

Results

Thirty key messages were agreed by both groups with seven of the key messages agreed by ≥95% of participants: dominant inheritance, the availability of predictive testing, the importance of pre-test discussion, increased risk of breast and ovarian cancer and the option of risk reducing mastectomy and bilateral salpingo-oophorectomy. Both groups agreed that key messages should be communicated pre- and post genetic testing.

Conclusions

There was a high level of agreement within and between the groups about the information requirements of women with breast/ovarian cancer about BRCA1/BRCA2. These key messages will be helpful in developing new approaches to the delivery of information as genetic testing becomes further integrated into mainstream oncology services.

Hormonal and reproductive factors and the risk of ovarian cancer

abstract
 

Purpose

Hormone-related factors have been associated with ovarian cancer, the strongest being parity and oral contraceptive use. Given reductions in birth rates and increases in oral contraceptive use over time, associations in more recent birth cohorts may differ. Furthermore, consideration of ovarian cancer heterogeneity (i.e., Type I/II invasive cancers) may contribute to a better understanding of etiology. We examined hormone-related factors in relation to ovarian cancer risk overall, for Type I and Type II cancers, as well as borderline tumors.

Methods

A population-based case–control study was carried out in Montreal, Canada from 2011 to 2016, including 496 cases and 908 controls. For each hormone-related variable, adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression for ovarian cancer overall, and using polytomous logistic regression for associations by tumor behavior and ovarian cancer type.

Results

Parity was inversely associated with risk overall and by tumor behavior and type, with a stronger OR for Type I for ≥3 full-term births vs. nulliparity] vs. Type II invasive cancers; the OR for borderline tumors was 0.41. Oral contraceptive ever use was not associated with risk overall, but ≥10 years of use vs. never use reduced risk, particularly for invasive cancers. A history of endometriosis was most strongly associated with Type I cancers. Associations with other factors were less clear.

Conclusions

These results suggest that associations with some hormone-related factors may differ between borderline and invasive Type I and II ovarian cancers.

Enrichment of putative PAX8 target genes at serous epithelial ovarian cancer susceptibility loci

Abstract
 

Conclusions:

Putative PAX8 target genes are enriched for common SOC risk variants. This finding from our agnostic evaluation is of particular interest given that PAX8 is well-established as a specific marker for the cell of origin of SOC.

Background:

Genome-wide association studies (GWAS) have identified 18 loci associated with serous ovarian cancer (SOC) susceptibility but the biological mechanisms driving these findings remain poorly characterised. Germline cancer risk loci may be enriched for target genes of transcription factors (TFs) critical to somatic tumorigenesis.

Immune checkpoint inhibitors in malignancies with mismatch repair deficiency: a review of the state of the current knowledge

abstract

 The use of immune checkpoint inhibitors to treat malignant tumors with microsatellite instability is an emerging new modality. This is based on the observations that these tumors may have a high mutation rate—thus a potential source of tumor-specific neoantigens—and harbor infiltrating cytotoxic T cells in response, suggesting that they may be particularly susceptible to immune checkpoint therapy. PUBMED and ASCO library were systematically reviewed to identify all relevant data that involved the use of immune checkpoint inhibitors in the treatment of cancers with microsatellite instability. The manual search retrieved a total of 3 relevant articles and 1 abstract published between 2015 and 2016. A total of 61 patients with colorectal, 3 with ampullary/cholangiocarcinoma, 2 with endometrial carcinomas, 3 with small bowel cancers, 2 with glioblastoma multiforme, and 1 with bladder cancer with reported efficacy results were reviewed. All the patients had stage IV cancer and were treated with immune checkpoint inhibitors until progression of disease or intolerable side effects emerged. The range of objective response rate was 25–71%. Responses were also durable with progression-free survival at 20 weeks of around 67–78% and to 46% at 1 year. The use of immune checkpoint inhibitors is effective in cancers that express microsatellite instability.

Conflicts of interest in medicine: pervasive, worrisome, and detrimental to healthcare

HealthNewsReview.org

 It also underscores how difficult it has become for healthcare providers and journalists to keep up with an increasingly entangled web of COI. It makes me wonder: how can we expect the public to navigate it?

Is Canadian research falling prey to predatory journals?

Healthy Debate
  January 19, 2017

Author: Karen Palmer, Timothy Caulfield & Maureen Taylor

---

‘The costs are huge’

“Experienced and inexperienced researchers are getting caught up in this,” says David Moher, a senior scientist in the Clinical Epidemiology Program and director of the Centre for Journalology at the Ottawa Hospital Research Institute.....

 Almost everyone agrees that publish or perish is part of the problem.

Institute for Clinical Immuno-Oncology White Paper Highlights the Challenges, Progress, and Priorities in Immunotherapy

The ASCO Post


The white paper, Immuno-Oncology: There’s More to Discover, spotlights top-level concerns for the future of immunotherapy in practice, including the following issues:

• Payer and coverage policies continue to pose barriers to access to immunotherapies for cancer. Thus, providers in the community have an ongoing need for education and strategies to effectively address prior authorization requirements, claims denials, and expanded access to clinical trials.
• Patients are driving discussions about expanded access to immunotherapies. Direct-to-consumer and other media advertising is fueling interest in immunotherapies. At the same time, this consumer interest is requiring ongoing education so that consumers understand the patient populations for whom these therapies are appropriate and to ensure that both providers and patients are equipped to discuss the benefits and risks of a particular immunotherapy.
• Recognition and management of immune-related adverse events continue to create additional expense and resource requirements across the continuum of care. Community providers are likely to see increasing challenges in this area as new indications and new combination therapies are approved by the U.S. Food and Drug Administration (FDA). Education on how to leverage operational assets and marshal resources to adequately recognize and manage immune-related adverse events will continue to be important.
• Alternative payment models (APMs) focused on value-based reimbursement must include input and buy-in from the oncology community. There is concern that APMs could be developed without oncologist input, peer review, or evidence concerning immunotherapies for cancer. Ultimately, APMs will need to create and utilize quality measures that promote innovation rather than simply drive down costs, because it is often challenging to identify what a therapy’s value is until providers use it in a real-world context.

OA: Internet Health Information Seeking and the Patient-Physician Relationship: A Systematic Review

JMIR-Internet Health Information Seeking and the Patient-Physician Relationship: A Systematic Review | Tan | Journal of Medical Internet Research
 Published on 19.01.17

  Discussion
Principal Findings

Based on our review of the 18 empirical studies that examined patients’ Internet health information seeking and the implications for the patient-physician relationship, we found that a greater proportion of patients did not feel that their Internet health information-seeking activities had an adverse impact on the patient-physician relationship [3,29,33,34]. The recent proliferation of health information on the Internet has resulted in a shift in the traditional information balance [37,38], where patients are increasingly equipped with health information related to their conditions, eroding the prior exclusivity of health information among health professionals. However, our findings show that patients’ positive attitude toward physicians did not change unless physicians imposed restrictions on their online information sharing during consultations (eg, [3,7,26]). Patients went on the Internet mostly to be actively involved in the decision making related to their health. Patients still valued consultations with physicians [27], and their trust in physicians remained very high [26,27]. Patients used the information found on the Internet to help them prepare for their visit, ask better questions, and understand what the physicians told them. These were shown to empower patients to play a more active role in their disease management and to be more effective in understanding and communicating with their physicians [32]. Internet-informed patients were also more confident in and comfortable with their physicians’ advice [15].

In the studies we reviewed, some looked at how Internet health information seeking affected the patient-physician relationship, while others focused on how patients’ use of the online health information affected the patient-physician relationship. Although we identified 5 different types of strategies in the literature (including silently verifying information, bringing printouts, explicitly verifying information by asking questions, and asking extra questions without directly revealing their Internet search), most studies focused simply on whether patients discussed the online health information during physician consultations and the associated outcomes. Among these studies, evidence showed that patients experienced a better patient-physician relationship when they had the opportunity to discuss their online health information with their physicians, and their physicians were receptive to discussing the online information. However, if patients experienced resistance from their physicians to their discussion of online information, patients were found to become frustrated and anxious [7] and would withhold their discussion [3,7]. Conflicts arising from physicians and patients having different interpretations of the online information and when patients valued this information more also had adverse implications for the patient-physician relationship [12]. In general, we found more evidence of positive than of negative implications of discussing online health information.

As patients become better informed and like to be more actively involved in decision making about their health, traditional models of the patient-physician relationship need to be adapted to patients’ changing needs by incorporating their perspective into a relationship-centered medical paradigm [39]. In contrast to the physician-centric paternalistic models of care, a deliberative or participatory model has been recommended for encounters with Internet-informed patients [40], where physicians delineate the patients’ clinical situation and provide help in explaining and deciding on the available options [41]. Under this model of care, the physician acts as a teacher or a friend by engaging patients in a dialogue through the decision-making process [39].

Allowing or encouraging patients to discuss their Internet information searches with physicians is increasingly important, given that acquiring information on the Internet has the potential to misguide patients with inaccurate information and make them excessively anxious [8]. Therefore, the information patients wish to use in decision making ought to be verified to ensure that it is based on facts [40]. Additionally, not disclosing their Internet information searches could erode patients’ trust in their physicians if the diagnosis or the recommendations are different from their Internet research findings [2]. Our findings showed that enabling patients to communicate their Internet research was one of the key mechanisms to ensure that patients’ opinion was valued and to enhance physicians’ relationships with their Internet-informed patients. When physicians embrace openness to online information [7,12,15,24] and encourage patients to discuss the online information they have, patients’ perception of physician resistance and fear of embarrassment could be reduced and patients are more likely to discuss online information with their physicians.

Genetics Play an Important Role in Assessing Brain Cancer Risk and Treatment (interview)

Interview

 Assessing a patient’s risk for brain tumors, and other tumor types, based on genetic testing can be a complex and complicated process—one that genetic counselors can help with, says Krista Qualmann, MS, CGC....Qualmann discussed the syndromes she is identifying in patients in her clinic, as well as how they could impact treatment, in an interview with Targeted Oncology.

  The genetic testing that I’m talking to patients about is genetic testing either on a blood or saliva sample to look for a gene mutation that they were born with. Very common syndromes could include things like Li-Fraumeni syndrome, von Hippel-Lindau disease, Lynch syndrome, and a couple more.

 For Li-Fraumeni syndrome, almost every type of cancer that you can think of has been seen in at least a couple of patients. I think they have narrowed it down to 4 or 5 of the most common, but then they’re also at a very high risk for other cancers. For women specifically with Li-Fraumeni syndrome, they have a very high lifetime risk of any cancer because of their really high risk for breast cancer, which isn’t necessarily seen in men.

Dr. Markman on Combination Treatments in Ovarian Cancer

video/text

Medical Oncologists' Experiences in Using Genomic Testing for Lung and Colorectal Cancer Care

abstract

PURPOSE:

Genomic testing improves outcomes for many at-risk individuals and patients with cancer; however, little is known about how genomic testing for non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC) is used in clinical practice.

PATIENTS AND METHODS:

In 2012 to 2013, we surveyed medical oncologists who care for patients in diverse practice and health care settings across the United States about their use of guideline- and non-guideline-endorsed genetic tests. Multivariable regression models identified factors that are associated with greater test use.

RESULTS:

Of oncologists, 337 completed the survey (participation rate, 53%). Oncologists reported higher use of guideline-endorsed tests (eg, KRAS for CRC; EGFR for NSCLC) than non-guideline-endorsed tests (eg, Onco typeDX Colon; ERCC1 for NSCLC). Many oncologists reported having no patients with CRC who had mismatch repair and/or microsatellite instability (24%) or germline Lynch syndrome (32%) testing, and no patients with NSCLC who had ALK testing (11%). Of oncologists, 32% reported that five or fewer patients had KRAS and EGFR testing for CRC and NSCLC, respectively. Oncologists, rather than pathologists or surgeons, ordered the vast majority of tests. In multivariable analyses, fewer patients in nonprofit integrated health care delivery systems underwent testing than did patients in hospital or office-based single-specialty group settings (all P < .05). High patient volume and patient requests (CRC only) were also associated with higher test use (all P < .05).

CONCLUSION:

Genomic test use for CRC and NSCLC varies by test and practice characteristics. Research in specific clinical contexts is needed to determine whether the observed variation reflects appropriate or inappropriate care. One potential way to reduce unwanted variation would be to offer widespread reflexive testing by pathology for guideline-endorsed predictive somatic tests.

Rare germline alterations in cancer-related genes associated with the risk of multiple primary tumor development

abstract

 KEY MESSAGE:
CNVs may explain the risk of hereditary cancer syndromes in MPT patients. CNVs affecting genes related to cancer are candidates to be involved in MPT risk. EPCAM/MSH2 deletions should be investigated in patients suspected to have LS.

Supplementary materials (eg. 1st-4th primary, variants)

Clinico-pathological information of the 22 patients enrolled in the study

Rucaparib Camsylate - National Cancer Institute new drug summary

Rucaparib Camsylate - National Cancer Institute

Global differences in cancer drug prices: a comparative analysis

video 4:27min

Hamilton woman who faked cancer gets 2 years for fraud

Toronto Star

What Influences a Woman’s Decision to Stop Chemopreventive Therapy for Breast Cancer?

The ASCO Post

 Key Points

• Worsening of menopause-specific quality of life was associated with early discontinuation of chemopreventive therapy with aromatase inhibitors.
• Worsening in vasomotor, sexual, physical, and psychosocial domains were each associated with early treatment discontinuation.

Study Details
In the MAP.3 trial, 4,560 high-risk postmenopausal women were randomized between 2004 and 2010 to receive exemestane at 25 mg or placebo for 5 years. The current analysis included 4,501 participants, who completed the Menopause-Specific Quality-of-Life Questionnaire (MENQOL) at study entry and at 6 months.

Why Medical Advice Seems to Change So Frequently

The New York Times

Urology, gynecology collaboration addresses rising demand

Urology Times

In the past, there were tremendous turf battles between gynecology and urology. When one tried to impinge on the other’s territory, it was usually the dean who became involved. What do you think drove the change to cooperation we see now?

I think one of the main factors was each specialty realizing that neither one could completely “own” this set of clinical problems and that we need each other. Urology would need the OB/GYN expertise, and OB/GYN would need the urology expertise to make any progress in terms of research, patient care, and professional training.....

 

Editorial/Paper: (Lynch Syndrome) Confirmation of ProMisE: A simple, genomics-based clinical classifier for endometrial cancer

abstract

See editorial on pages The promise of molecular staging for the future, this issue.

Editorial: (abstract)

Molecular profiling is becoming increasingly powerful in characterizing cancers. This technology should be used to augment the traditional anatomic and histologic staging of all cancers and particularly of endometrial cancers.

Abstract

BACKGROUND

Classification of endometrial carcinomas (ECs) by morphologic features is irreproducible and imperfectly reflects tumor biology. The authors developed the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE), a molecular classification system based on The Cancer Genome Atlas genomic subgroups, and sought to confirm both feasibility and prognostic ability in a new, large cohort of ECs.

METHODS

Immunohistochemistry (IHC) for the presence or absence of mismatch repair (MMR) proteins (to identify MMR deficiency [MMR-D]), sequencing for polymerase-ɛ (POLE) exonuclease domain mutations (POLE EDMs), and IHC for tumor protein 53 (p53) (wild type vs null/missense mutations; p53 wt and p53 abn, respectively) were performed on 319 new EC samples. Subgroups were characterized and assessed relative to outcomes. The prognostic ability of ProMisE was compared with that of current risk-stratification systems (European Society of Medical Oncology [ESMO]).

RESULTS

ProMisE decision-tree classification achieved categorization of all cases and identified 4 prognostic subgroups with distinct overall, disease-specific, and progression-free survival (P < .001). Tumors with POLE EDMs had the most favorable prognosis, and those with p53 abn the worst prognosis, and separation of the 2 middle survival curves (p53 wt and MMR-D) was observed. There were no significant differences in survival between the ESMO low-risk and intermediate-risk groups. ProMisE improved the ability to discriminate outcomes compared with ESMO risk stratification. There was substantial overlap (89%) between the p53 abn and high-risk ESMO subgroups; but, otherwise, there were no predictable associations between molecular and ESMO risk groups.

CONCLUSIONS

Molecular classification of ECs can be achieved using clinically applicable methods and provides independent prognostic information beyond established clinicopathologic risk factors available at diagnosis. Consistent, biologically relevant categorization enables stratification for clinical trials and/or targeted therapy, identification of women who are at increased risk of having Lynch syndrome, and may guide clinical management.

Cochrane: Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases

Cochrane
 

Authors' conclusions: 

We found no evidence to support antioxidant supplements for primary or secondary prevention. Beta-carotene and vitamin E seem to increase mortality, and so may higher doses of vitamin A. Antioxidant supplements need to be considered as medicinal products and should undergo sufficient evaluation before marketing.

BBC - Future - Why vitamin pills don't work, and may be bad for you

BBC

A 'civil war' over painkillers rips apart the medical community (eg. opioids)

medical news

2017 program: ASCO-SITC Clinical Immuno-Oncology Symposium

Program 

About

The ASCO-SITC Clinical Immuno-Oncology Symposium is a three-day meeting focused on clinical and translational research in immuno-oncology and the implications for clinical care. This is a new meeting, one that will address the high-level of need for clinical education in a field where all aspects of care are fundamentally different from traditional therapies.
Practitioners and researchers alike will benefit from this meeting's emphasis on clinical and translational research in immuno-oncology and implications for clinical care across a wide range of disease sites. The Symposium Program is full of educational sessions discussing exciting new research and its clinical application, as well as keynote lectures from world-renowned speakers addressing the most progressive and pertinent issues in immuno-oncology. The Symposium also includes poster sessions highlighting the latest, breakthrough science in the field and multiple opportunities for networking with faculty members and fellow attendees.

Why Should You Attend This New Meeting?

• CONNECT: Meet faculty members and fellow attendees from around the world in both formal and informal networking events.
  
• DISCOVER: Attend education and science sessions that explore pioneering clinical and translational research and breakthroughs in immuno-oncology and its implications for patient care.
  
• ENGAGE: Ask expert faculty your most pressing questions in extended Question and Answer panels. Visit the exhibits to expand your understanding of the most advanced therapies, products, and upcoming research.
  

 

Systematic drug sensitivity testing reveals synergistic growth inhibition by dasatinib or mTOR inhibitors with paclitaxel in ovarian granulosa cell tumor cells

abstract:
Systematic drug sensitivity testing reveals synergistic growth inhibition by dasatinib or mTOR inhibitors with paclitaxel in ovarian granulosa cell tumor cells

 Highlights

•

Systematic drug and molecular profiling discovers new therapies in ovarian cancer.

•

AGCT cells show selective sensitivity to a TKI dasatinib and mTOR inhibitors.

•

Dasatinib or mTOR inhibitors synergize with paclitaxel in AGCT cells. (ovarian granulosa cell tumor)

Methods

The responses of three primary and four recurrent AGCTs to 230 anticancer compounds were screened in vitro using a systematic drug sensitivity and resistance testing (DSRT) platform, coupled with mRNA sequencing. The responses of the AGCTs were compared with those of human granulosa luteal cells and bone marrow mononuclear cells.

Case Report: Ductal Carcinoma in situ Detected during Prospective MR Imaging Screening of a Woman with a BRCA2 Mutation (Japan)

pdf

( Japanese HBOC Con-sortium) They found that HBOC may have nearly the same prevalence in Japan as in the US or Europe. Thus, a nation-wide database of HBOC is thought to be very important for developing risk models for BRCA1/2 carriers in Japan.

 Case Report

A 48-year-old woman presented with no particular chief  complaints and no right nipple discharge.

Family History: Her sister (second daughter) had develped breast cancer at the age of 30 years, another sister (third daughter) also had breast cancer at the age of 36 years

and had tested positive for a BRCA2 mutation, her mother had suffered breast cancer at the age of 53 years, and her mother’s sister (second daughter) also had breast cancer at the age of 52 years and ovarian or uterine cancer at the age of 58 years (Fig. 1).

Past History: No cancer and no particular disease.

Why did Beall's List of potential predatory publishers go dark?

Retraction Watch at Retraction Watch

 The site, scholarlyoa.com, which just earlier this month included a list of more than 1,000 such publishers, now contains no information. The sudden change was noted Sunday on Twitter

(ovarian cancer) Clinigen Release Company Initiates U S Managed Access Program For Tesaros Niraparib

Clinigen Release Company Initiates U S Managed Access Program For Tesaros Niraparib For Patients With Ovarian Cancer

1/17/2017

  The Managed Access program allows physicians to request niraparib for individual, eligible U.S. patients who may not be able to participate in a clinical trial nor have any other treatment option, but who may benefit from access to this investigational therapy prior to approval.

Parity, infertility, oral contraceptives, and HRT and the risk of ovarian serous borderline tumors

abstract:
Parity, infertility, oral contraceptives, and hormone replacement therapy and the risk of ovarian serous borderline tumors: A nationwide case-control study

 Highlights

•

Parity and use of oral contraceptives are both highly protective factors in development of an ovarian serous borderline tumor

•

Infertility and use of hormone replacement therapy are risk factors for developing an ovarian serous borderline tumor

•

An ovarian serous borderline tumor and serous ovarian cancer seem to share some similar risk factors

journal index - Gynecologic Oncology (February 2017)

Gynecologic Oncology

NIH Charts a Path for Nutrition Science (U.S.)

The JAMA Network

Ontario doctors’ group could oust leaders after accusing them of failings

The Globe and Mail

Low-dose aspirin use and survival in breast cancer patients (UK)

abstract
 Conclusion

In this large nationwide study of breast cancer patients, we found little evidence of an association between post-diagnostic low-dose aspirin use and cancer-specific mortality.

Long-term hormone therapy for perimenopausal and postmenopausal women - The Cochrane Library

abstract
 
Editorial Group: Cochrane Gynaecology and Fertility Group

Published Online: 17 JAN 2017

Plain language summary

Long-term hormone therapy for perimenopausal and postmenopausal women

Review question
In perimenopausal and postmenopausal women, what are the clinical effects of using hormone therapy (HT) for a year or longer?
Background
HT is given for control of menopausal symptoms. It has also been used for the management and prevention of chronic diseases such as cardiovascular disease, osteoporosis and dementia.
Study characteristics
This review included 22 double-blinded randomised controlled trials (RCTs) (43,637 women). The evidence is current to September 2016.

Key results
In relatively healthy postmenopausal women, using combined continuous HT for 1 year increased the risk of a heart attack from about 2 per 1000 to between 3 and 7 per 1000, and increased the risk of venous thrombosis (blood clot) from about 2 per 1000 to between 4 and 11 per 1000. With longer use, HT also increased the risk of stroke, breast cancer, gallbladder disease and death from lung cancer.
Oestrogen-only HT increased the risk of venous thrombosis after 1 to 2 years' use: from 2 per 1000 to 2 to 10 per 1000. With longer use, it also increased the risk of stroke and gallbladder disease, but it reduced the risk of breast cancer (after 7 years' use) from 25 per 1000 to between 15 and 25 per 1000.
Among women over 65 years of age taking continuous combined HT, the incidence of dementia was increased.
Risk of fracture was the only outcome for which results showed strong evidence of clinical benefit from HT (both types).
Women with intolerable menopausal symptoms may wish to weigh the benefits of symptom relief against the small absolute risk of harm arising from short-term use of low-dose HT, provided they do not have specific contraindications. HT may be unsuitable for some women, including those at increased risk of cardiovascular disease, increased risk of thromboembolic disease (such as those with obesity or a history of venous thrombosis) or increased risk of some types of cancer (such as breast cancer, in women with a uterus). The risk of endometrial cancer for women with a uterus who take oestrogen-only HT is well documented.

HT is not indicated for primary or secondary prevention of cardiovascular disease or dementia, nor for preventing deterioration of cognitive function in postmenopausal women. Although HT is considered effective for prevention of postmenopausal osteoporosis, it is generally recommended as an option only for women at significant risk, for whom non-oestrogen therapies are unsuitable. Data are insufficient for assessment of the risk of long-term HT use in perimenopausal women or postmenopausal women younger than 50 years of age.

Quality of the evidence
For most studies, risk of bias was low in most domains and the overall quality of the evidence was moderate. The main limitation was that only about 30% of women were 50 to 59 years old at baseline - the age at which women are likely to consider HT for vasomotor symptoms.

CME: More Chemo May Not Equal Better Outcomes in Ovarian early stage (clear cell) Cancer

Medpage Today

Action Points

• Recurrence and survival in patients with early stage ovarian clear cell carcinoma (OCCC) were similar in those receiving 3 versus 6 cycles of platinum with or without taxane adjuvant chemotherapy, in a retrospective multi-institutional cohort.
• Note that the study was statistically underpowered and further clinical trials, including the use of novel agents, are needed to better illuminate the best strategy for treating early stage OCCC.

abstract
 Three versus six cycles of adjuvant platinum-based chemotherapy in early stage clear cell ovarian carcinoma – A multi-institutional cohort 
Published online: December 12, 2016

Is Mirvetuximab Soravtansine Active in Platinum-Resistant Ovarian Cancer? ( IMGN853)

The ASCO Post
 Key Points

• Mirvetuximab soravtansine produced response in 26% of patients with FRα-positive platinum-resistant ovarian cancer.
• Response rate and progression-free survival were higher in patients with up to three prior lines of treatment.

Moore et al found that mirvetuximab soravtansine (also known as IMGN853)—an antibody-drug conjugate targeting folate receptor alpha (FRα)—is active in FRα-positive platinum-resistant ovarian cancer, according to a phase I expansion cohort study reported in the Journal of Clinical Oncology.

Study Details
In the study, 46 patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer received mirvetuximab soravtansine at 6.0 mg/kg (adjusted ideal body weight) once every 3 weeks. Patients had to be FRα-positive on immunohistochemistry, defined as ≥ 25% of tumor cells with ≥ 2+ staining intensity.

Response Rates and Adverse Events
Among all patients, the confirmed objective response rate was 26%, including a complete response in 1 patient and a partial response in 11 patients; the median progression-free survival was 4.8 months; and the median duration of response was 19.1 weeks. Among 23 patients with ≤ 3 prior lines of therapy, the objective response rate was 39%, the median progression-free survival was 6.7 months, and the median duration of response was 19.6 weeks.
The most common treatment-related adverse events of any grade were diarrhea (44%), blurred vision (41%), nausea (37%), and fatigue (30%). Grade 3 fatigue and grade 3 hypotension each occurred in 2 patients (4%), with no other grade 3 event occurring in > 1 patient.

interview (book author Stephen Klasko 34:33 min) U.S.: We CAN Fix Healthcare: The Future is NOW

• Blogger's Note: not sure of the date of this interview

     ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

  Interview:

   Host John J. Russell, MD

  Dr. Stephen Klasko, President and CEO of Jefferson University, discusses ways to improve the American healthcare system

  Overview

  
  

  What if Americans put aside their differences and worked together to fix America's broken healthcare system? What changes need to be made in order to make health care both accessible and affordable without compromising excellent quality of care standards for patients? These and other crucial questions form premise behind the book We CAN Fix Healthcare: The Future is NOW.
  Host Dr. John Russell sits down with Dr. Stephen Klasko, President and CEO of Jefferson University and Jefferson Health and author of We CAN Fix Healthcare: The Future is NOW.

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What is Cochrane? | Cochrane


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