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Posts Tagged ‘BRCA mutation’


Elephants and cancer

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

In 1992, I moved to the Washington DC area and attended a conference on new and projected trends in cancer care at the National Institutes of Health.

Researchers in Texas are now reporting that there may be a smarter way to combat cancer-associated KRAS (Kirsten rat sarcoma viral oncogene homolog) mutations and possibly attack specific tumor types in a new targeted manner.

A new study at a single center in Japan found no significant differences in the rate of BRCA mutations between ovarian cancer patients with or without family histories of the mutations and recommends that BRCA1/2 testing be required for all ovarian cancer patients

 

Why Elephants Don’t Get Cancer

Blog | October 30, 2015 | Cancer and Genetics
By Deborah A. Boyle, RN, MSN, AOCNS, FAAN

Image © Marchenko Yevhen/ Shutterstock.com
In 1992, I moved to the Washington DC area and attended a conference on new and projected trends in cancer care at the National Institutes of Health. A pediatric immunologist who treated and studied rare genetically-based childhood illnesses told the audience of oncology nurses that in the future there will be no need for surgery, radiation, or systemic antineoplastic therapies to treat cancer. Rather, genetic molecular engineering will be used to stop and reverse early signs of cancer and counter carcinogenesis even at later stages. I sat in the audience and was awestruck by this forecast. I found it unfathomable that this could ever become a reality.
Fast forward to 2015, over 20 years later, and I read in the science column of the Los Angeles Times the story entitled, “Elephants’ Anti-Cancer Secret” (October 10, 2015, p.B2). Reporting on a study published in a recent issue of JAMA,1, 2 the columnist shares the finding that elephants (and other large mammals) rarely get cancer. Scientists recently revealed the potential reason for such.

African elephants have twenty copies of a gene called TP53, which produces a protein that suppresses tumor growth. Humans on the other hand, have only one copy of this gene. Collaborating with a zookeeper at Utah’s Hogle Zoo in Salt Lake City and the chief veterinarian for Ringling Bros. Barnum and Bailey Circus, the researchers also identified that elephants were able to make copies of TP53 such that they were incorporated into the genome over time. Additionally, when the elephants’ cells were exposed to radiation, cell death occurred at twice the rate of human cells.

In recent years, the advent of targeted therapies and the identification of genes associated with heightened cancer risk have put the spotlight on genetics in the management of cancer.

The implications of this research will undoubtedly help keep the focus on this critical area of cancer research. The scientists involved in this investigation posited that perhaps a drug could be created that mimics the actions of TP53 or that the insertion of TP53 genes into precancerous cells could reverse mutations. Since it took millions of years for the elephants of today to evolve, I guess waiting 20 years for this type of knowledge to come forth isn’t that long to wait.

I’ve become a believer in the profound possibility of genetics in cancer therapy. That physician I heard decades ago was “right on.”

REFERENCES

Abegglen LM, Caulin AF, Chan A, et al. (2015).
Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans.
JAMA, Oct 8:1-11. http://dx.doi.org:/10.1001/jama.2015.13134.
Greaves M, Ermini L. (2015).
Evolutionary Adaptation to Risk of Cancer: Evidence From Cancer Resistance in Elephants.
JAMA, Oct 8:1-3. http://dx.doi.org:/10.1001/jama.2015.13153.
– See more at: http://www.oncotherapynetwork.com/cancer-and-genetics/why-elephants-dont-get-cancer#sthash.5xGzcSFp.dpuf

 

Researchers Develop New Classification Model for Cancer-Associated KRAS Mutations

News | October 28, 2015 | Cancer and Genetics
By John Schieszer
Researchers in Texas are now reporting that there may be a smarter way to combat cancer-associated KRAS (Kirsten rat sarcoma viral oncogene homolog) mutations and possibly attack specific tumor types in a new targeted manner. They are reporting that the use of biochemical profiling and sub classification of KRAS-driven cancers may lead to a more rational selection of therapies targeting specific KRAS isoforms or specific RAS effectors.
KRAS is one of the main members of the RAS family. About one-third of all human cancers, including a high percentage of pancreatic, lung, and colorectal cancers, are driven by mutations in RAS genes, which also make cells resistant to some available cancer therapies, according to the National Cancer Institute.

The UT Southwestern Medical Center researchers have developed a new classification for cancers caused by KRAS. They are investigating a new strategy based on models that the researchers developed to classify cancers caused by KRAS mutations, which cause cells to grow uncontrollably. Although KRAS-driven cancer mutations have long been a focus of cancer research, effective targeted therapies are not available.

“This work further supports the idea that not all oncogenic KRAS mutations function in the same way to cause cancer. The model we developed may help in sub classifying KRAS-mutant cancers so they can be treated more effectively, using therapies that are tailored to each mutation,” said Kenneth Westover, MD, who is an as Assistant Professor of Radiation Oncology and Biochemistry at the University of Texas Southwestern Medical Center, in a news release.1 “Furthermore, this study gives new fundamental understanding to why certain KRAS-mutant cancers, for example those containing the KRAS G13D mutation, behave as they do.”

The researchers, who have published their findings in Molecular Cancer Research, have characterized the most common KRAS mutants biochemically for substrate binding kinetics, intrinsic and GTPase-activating protein (GAP)–stimulated GTPase activities, and interactions with the RAS effector, RAF kinase. They report that KRAS G13D appears to show rapid nucleotide exchange kinetics compared with other mutants analyzed.2

In this study, the researchers evaluated eight of the most common KRAS mutants for key biochemical properties including nucleotide exchange rates, enzymatic activity, and binding activity related to a key signaling protein, RAF kinase. The researchers observed significant differences between the mutants, including about a tenfold increase in the rate of nucleotide exchange for the specific mutant KRAS G13D, highly variable KRAS enzymatic activities, and variability in affinity for RAF. They also determined high-resolution, three-dimensional X-ray crystal structures for several of the most common mutants, which led to a better understanding of some of the biochemical activities observed.

The researchers now plan to test their models in more complex experimental systems, such as genetically engineered cancer cell lines.

REFERENCES

UT Southwestern Medical Center. (2015).
Researchers develop classification model for cancers caused by most frequently mutated cancer gene.
Hunter JC, Manandhar A, Carrasco MA, et al. (2015).

Biochemical and Structural Analysis of Common Cancer-Associated KRAS Mutations.
Molecular Cancer Research, Sep;13(9):1325-35.
– See more at: http://www.oncotherapynetwork.com/cancer-and-genetics/researchers-develop-new-classification-model-cancer-associated-kras-mutations#sthash.kkK8G0Mi.dpuf

 

 

 

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Good and Bad News Reported for Ovarian Cancer Therapy

Reporter, Curator: Stephen J. Williams, Ph.D.

 

In a recent Fierce Biotech report

FDA review red-flags AstraZeneca’s case for ovarian cancer drug olaparib”,

John Carroll reports on a disappointing ruling by the FDA on AstraZeneca’s PARP1 inhibitor olaparib for maintenance therapy in women with cisplatin refractory ovarian cancer with BRCA mutation.   Early clinical investigations had pointed to efficacy of PARP inhibitors in ovarian tumors carrying the BRCA mutation. The scientific rationale for using PARP1 inhibitors in BRCA1/2 deficiency was quite clear:

  1. DNA damage can result in

1. double strand breaks (DSB)

  1.  DSB can be repaired by efficient homologous recombination (HR) or less efficient non-homologous end joining (NHEJ)

b. BRCA1 involved in RAD51 dependent HR at DSB sites

  1. In BRCA1 deficiency DSB repaired by less efficient NHEJ

 

 

2. single strand breaks, damage (SSB)

  1. PARP1 is activated by DNA damage and poly-ADP ribosylates histones and other proteins marking DNA for SSB repair
  2. SSB repair usually base excision (BER) or sometimes nucleotide excision repair (NER)

B. if PARP inhibited then SSB gets converted to DSB

C. in BRCA1/2 deficient background repair is forced to less efficient NHEJ thereby perpetuating some DNA damage pon exposure to DNA damaging agent

 

A good review explaining the pharmacology behind the rationale of PARP inhibitors in BRCA deficient breast and ovarian cancer is given by Drs. Christina Annunziata and Susan E. Bates in PARP inhibitors in BRCA1/BRCA2 germline mutation carriers with ovarian and breast cancer

(http://f1000.com/prime/reports/b/2/10/) and below a nice figure from their paper:

 

parpbrcadnadamage

 

 

 

 

 

 

 

(from Christina M Annunziata and Susan E Bates. PARP inhibitors in BRCA1/BRCA2 germline mutation carriers with ovarian and breast cancer.  F1000 Biol Reports, 2010; 2:10.)  Creative Commons

Dr. Sudipta Saha’s post BRCA1 a tumour suppressor in breast and ovarian cancer – functions in transcription, ubiquitination and DNA repair discusses how BRCA1 affects the double strand DNA repair process, augments histone modification, as well as affecting expression of DNA repair genes.

Dana Farber’s Dr. Ralph Scully, Ph.D., in Exploiting DNA Repair Targets in Breast Cancer (http://www.dfhcc.harvard.edu/news/news/article/5402/), explains his research investigating why multiple DNA repair pathways may have to be targeted with PARP therapy concurrent with BRCA1 deficiency.

 

However FDA investigators voiced their skepticism of AstraZeneca’s clinical results, namely

  • Small number of patients enrolled
  • BRCA1/2 cohort were identified retrospectively
  • results skewed by false benefit from “underperforming” control arm
  • possible inadvertent selection bias
  • hazard ratio suggesting improvement in progression free survival but higher risk/benefit

The FDA investigators released their report two days before an expert panel would be releasing their own report (reported in the link below from FierceBiotech)

UPDATED: FDA experts spurn AstraZeneca’s pitch for ovarian cancer drug olaparib

in which the expert panel reiterated the findings of the FDA investigators.   The expert panel’s job was to find if there was any clinical benefit for continuing consideration of olaparib, basically stating

“This trial has problems,” noted FDA cancer chief Richard Pazdur during the panel discussion. If investigators had “pristine evidence of a 7-month advantage in PFS, we wouldn’t be here.”

The expert panel was concerned for the above reasons as well as the reported handful of lethal cases of myelodysplastic syndrome and acute myeloid leukemia in the study, although the panel noted these patients had advanced disease before entering the trial, raising the possibility that prior drugs may have triggered their deaths.

 

This was certainly a disappointment as ….

it was at last year’s ASCO (2013) that investigators at Perelman School of Medicine at the University of Pennsylvania and Sheba Medical Center in Tel Hashomer, Israel presented data showing that in 193 cisplatin-refractory ovarian cancer patients carrying a BRCA1/2 mutation, 31% had a partial or complete tumor regression. In addition the study also showed good response in pancreatic and prostate cancer with tolerable side effects.

 

See here for study details: http://www.uphs.upenn.edu/news/News_Releases/2013/05/domchek/

 

As John Carrol from FierceBiotech notes, the decision may spark renewed interest by Pfizer of a bid for AstraZeneca as the potential FDA rejection would certainly dampen AstraZeneca’s future growth and profit plans. Last month AstraZeneca’s CEO made the case to shareholders to reject the Pfizer offer by pointing to AstraZeneca’s potential beefed-up pipeline. AstraZeneca had projected olaparib as a potential $2 billion-a-year seller, although some industry analysts see sales at less than half that amount.

A company spokeswoman said the monotherapy use of olaparib for ovarian cancer assessed by the U.S. expert panel this week was only one element of a broad development program.

 

 

Please see a table of current oncology clinical trials with PARP1 inhibitors

at end of this post

 

However, on the same day, FierceBiotechreports some great news (at least in Europe) on the ovarian cancer front:

 

EU backs Roche’s Avastin for hard-to-treat ovarian cancer

As Arlene Weintraub   of FierceBiotech reports:

EU Committee for Medicinal Products for Human Use (CHMP) handed down a positive ruling on Avastin, recommending that the European Commission approve the drug for use in women with ovarian cancer that’s resistant to platinum-based chemotherapy. It’s the first biologic to receive a positive opinion from the CHMP for this hard-to-treat form of the disease.

Please see here for official press release: CHMP recommends EU approval of Roche’s Avastin for platinum-resistant recurrent ovarian cancer

 

EU had been getting pressure from British doctors to approve Avastin based on clinical trial results although it may be important to note that the EU zone seems to have an ability to recruit more numbers for clinical trials than in US. For instance an EU women’s breast cancer prevention trial had heavy recruitment in what would be considered a short time frame compared to recruitment times for the US.

 

Below is a table on PARP1 inhibitors in current clinical trials (obtained from NewMedicine’s Oncology KnowledgeBase™). nm|OK is a relational knowledgeBASE covering all major aspects of product development in oncolology. The database comprises 6 modules each dedicated in a specific sector within the oncology field.

 

PARP1 Inhibitors Currently in Clinical Trials for Ovarian Cancer

 

Developer and

Drug Name

Development Status & Location
– Indications
AbbVie

Current as of: March 27, 2014

PARP inhibitor: ABT-767

Phase I (begin 5/11, ongoing 2/14) Europe (Netherlands) – solid tumors with BRCA1 or BRCA2 mutations, locally advanced or metastatic • ovarian cancer, advanced or metastatic • fallopian tube cancer, advanced or metastatic • peritoneal cancer, advanced or metastatic
AstraZeneca
Affiliate(s):
· Myriad GeneticsCurrent as of: June 26, 2014Generic Name: Olaparib
Brand Name: Lynparza
Other Designation: AZD2281, KU59436, KU-0059436, NSC 747856
Phase I (begin 7/05, closed 9/08) Europe (Netherlands, UK, Poland); phase II (begin 6/07, closed 2/08, completed 5/09) USA, Australia, Europe (Germany, Spain, Sweden, UK), phase II (begin 7/08, closed 2/09) USA, Australia, Europe (Belgium, Germany, Poland, Spain, UK), Israel, phase II (begin 8/08, closed 12/09, completed 3/13) USA, Australia, Canada, Europe (Belgium, France, Germany, Poland, Romania, Spain, Ukraine, UK), Israel, Russia; phase II (begin 2/10, closed 7/10) USA, Australia, Canada, Europe (Belgium, Czech Republic, Germany, Italy, Netherlands, Spain, UK), Japan, Panama, Peru (combination); MAA (accepted 9/13) EU, NDA (filed 2/14) USA – ovarian cancer, advanced or metastatic, BRCA positive • ovarian cancer, recurrent, platinum sensitive • ovarian cancer, advanced, refractory, BRCA1 or BRCA2-associatedPhase I (begin 5/08, ongoing 5/12) USA; phase II (begin 7/08, closed 10/09) Canada – breast cancer, locally advanced, BRCA1/BRCA2-associated or hereditary metastatic or inoperable • ovarian cancer, locally advanced, BRCA1/BRCA2-associated or hereditary metastatic or inoperable • breast cancer, triple-negative, BRCA-positive • ovarian cancer, high-grade serous and/or undifferentiated, BRCA-positive

Phase I (begin 10/10, ongoing 1/13) USA (combination) – ovarian cancer, inoperable or metastatic, refractory • breast cancer, inoperable or metastatic, refractory

Phase III (begin 8/13) USA, Australia, Brazil, Canada, Europe (France, Italy, Netherlands, Poland, Russia, Spain, UK), Israel, South Korea, phase III (begin 9/13) USA, Australia, Brazil, Canada, Europe (France, Germany, Italy, Netherlands, Poland, Russia, Spain, UK), Israel – ovarian cancer, serous, high grade, BRCA mutated, platinum-sensitive, relapsed, third line, maintenance • ovarian cancer, serous or endometrioid, high grade, BRCA mutated, platinum responsive (PR or CR), maintenance, first line • primary peritoneal cancer, high grade, BRCA mutated, platinum responsive (PR or CR), maintenance • fallopian tube cancer, high grade, BRCA mutated, platinum responsive (PR or

BioMarin Pharmaceutical

Current as of: June 14, 2014

PARP inhibitor:

BMN-673, BMN673, LT-673

Phase I/II (begin 1/11, ongoing 3/14) USA – solid tumors, advanced, recurrent

Phase I (begin 2/13, closed 4/13, completed 5/14) USA – healthy volunteers

Phase I/II (begin 11/13) USA – solid tumors, relapsed or refractory, BRCA mutated, second line

BiPar Sciences

Current as of: April 16, 2009

Parp inhibitor:

BSI-401

Preclin (ongoing 4/09) – solid tumors
Clovis Oncology
Affiliate(s):
· University of Newcastle Upon Tyne
· Cancer Research Campaign Technology
· PfizerCurrent as of: June 21, 2014Generic Name: Rucaparib
Brand Name: Rucapanc
Other Designation: AG140699, AG014699, AG-14,699, AG-14669, AG14699, AG140361, AG-14361, AG-014699, CO-338, PF-01367338
Phase I (begin 03, completed 05) Europe (UK) (combination), phase I (begin 2/10, closed 11/13) Europe (France, UK) (combination) – solid tumors, advanced

Phase II (begin 12/07, closed 10/13) Europe (UK) – breast cancer, advanced or metastatic, in patients carrying BRCA1 or BRCA2 mutations • ovarian cancer, advanced or metastatic, in patients carrying BRCA1 or BRCA2 mutations

Phase I/II (begin 11/11, ongoing 6/14) USA, Europe (UK) – solid tumors, metastatic, with mutated BRCA • breast cancer, metastatic, HEr2 negative, with mutated BRCA

Sanofi

Current as of: June 03, 2013

Generic Name: Iniparib
Brand Name: Tivolza
Other Designation: BSI-201, NSC 746045, SAR240550

Phase I/Ib (begin 3/06, closed 3/10) USA (combination), phase I (begin 7/10, closed 11/10) USA, phase I (begin 9/10, ongoing 2/11) Japan (combination); phase Ib (begin 1/07, ongoing 1/11) USA (combination) – solid tumors, advanced, refractory
Phase II (begin 5/08, closed 1/09) USA – ovarian cancer, advanced, refractory, BRCA-1 or BRCA-2 associated • fallopian tube cancer, advanced, refractory, BRCA-1 or BRCA-2 associated • peritoneal cancer, advanced, refractory, BRCA-1 or BRCA-2 associated
Tesaro
Affiliate(s):
· MerckCurrent as of: May 18, 2014Generic Name: Niraparib
Other Designation: MK-4827, MK4827
Phase I (begin 9/08, closed 2/11) USA, Europe (UK) – solid tumors, locally advanced or metastatic • ovarian cancer, locally advanced or metastatic, BRCA mutant • chronic lymphocytic leukemia (CLL), relapsed or refractory • prolymphocytic leukemia, T cell, relapsed or refractory
Phase Ib (begin 11/10, closed 3/11, terminated 10/12) USA (combination) – solid tumors, locally advanced or metastatic • ovarian cancer, serous, high grade, platinum resistant or refractoryPhase III (begin 5/13, ongoing 5/14) USA – ovarian cancer, platinum-sensitive, high grade serous or BRCA mutant, chemotherapy responsive • fallopian tube cancer • primary peritoneal cancer
Teva Pharmaceutical Industries

Current as of: May 04, 2013

Designation:

CEP-9722

Phase I (begin 5/11, closed 11/12, terminated 10/13) USA, phase I (begin 6/09, closed 7/12, completed 1/12) Europe (France and UK) (combination) – solid tumors, advanced, third line
Phase I (begin 5/11, completed 1/13) Europe (France) (combination) – solid tumors, advanced • mantle cell lymphoma (MCL), advanced

 

 

Summary of Combination Ovarian Cancer Trials with Avastin (current and closed)

 

Indication in Development ovarian cancer, advanced, recurrent, persistent • ovarian cancer, progressive, platinum resistant, second line • fallopian tube cancer, progressive, platinum resistant, second line • primary peritoneal cancer, progressive, platinum resistant, second line
Latest Status Phase II (begin 4/02, closed 8/04) USA, phase II (begin 11/04, closed 10/05) USA; phase III (begin 10/09) Europe (Belgium, Bosnia and Herzegovina, Denmark, Finland, France, Germany, Greece, Italy, Netherlands, Norway, Portugal, Spain, Sweden), Turkey
Clinical History Refer to the Combination Trial Module for trials of Avastin in combination with various chemotherapeutic regimens.According to results from the AURELIA clinical trial (protocol ID: MO22224; 2009-011400-33; NCT00976911), the median PFS in women with progressive platinum resistant ovarian, fallopian tube or primary peritoneal cancer treated with Avastin in combination with chemotherapy, was 6.7 months compared to 3.4 months in those treated with chemotherapy alone for an HR of 0.48 (range =0.38–0.60).. In addition, the objective response rate was 30.9% in women treated with Avastin compared to 12.6% in those on chemotherapy (p=0.001). Certain AE (Grade 2 to 5) that occurred more often in the Avastin arm compared to the chemotherapy alone arm were high blood pressure (20% versus 7%) and an excess of protein in the urine (11% versus 1%). Gastrointestinal perforations and fistulas occurred in 2% of women in the Avastin arm compared to no events in the chemotherapy arm (Pujade-Lauraine E, etal, ASCO12, Abs. LBA5002).A multicenter (n=124), randomized, open label, 2-arm, phase III clinical trial (protocol ID: MO22224; 2009-011400-33; NCT00976911; http://clinicaltrials.gov/ct2/results?term=NCT00976911 ), dubbed AURELIA, was initiated in October 2009, in Europe (Belgium, Bosnia and Herzegovina, Denmark, Finland, France, Germany, Greece, Italy, Netherlands, Norway, Portugal, Spain, and Sweden), and Turkey, to evaluate the efficacy and safety of Avastin added to chemotherapy versus chemotherapy alone in patients with epithelial ovarian, fallopian tube or primary peritoneal cancer with disease progression within 6 months of platinum therapy in the first line setting. The trials primary outcome measure is PFS. Secondary outcome measures include objective response rate, biological PFS interval, OS, QoL, and safety and tolerability. According to the protocol, all patients are treated with standard chemotherapy with IV paclitaxel (80 mg/m²) on days 1, 8, 15 and 22 of each 4-week cycle; or IV topotecan at a dose of 4 mg/m² on days 1, 8 and 15 of each 4-week cycle, or 1.25 mg/kg on days 1-5 of each 3-week cycle; or IV liposomal doxorubicin (40 mg/m²) every 4 weeks. Patients (n=179) randomized to arm 2 of the trial are treated with IV Avastin at a dose of 10 mg/kg twice weekly or 15 mg/kg thrice weekly concomitantly with the chemotherapy choice. Treatment continues until disease progression. Subsequently, patients are treated with the standard of care. Patients in arm 1 (n=182), on chemotherapy only may opt to be treated with IV Avastin (15 mg/kg) three times weekly. The trial was set up in cooperation with the Group d’Investigateurs Nationaux pour l’Etude des Cancers Ovariens (GINECO) and was conducted by the international network of the Gynecologic Cancer Intergroup (GCIG) and the pan-European Network of Gynaecological Oncological Trial Groups (ENGOT), under PI Eric Pujade-Lauraine, MD, Hopitaux Universitaires, Paris Centre, Hôpital Hôtel-Dieu (Paris, France). The trial enrolled 361 patients and was closed as of May 2012..Results were presented from a phase II clinical trial (protocol ID: CDR0000068839; GOG-0170D; NCT00022659) of bevacizumab in patients with persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer that was performed by the Gynecologic Oncology Group to determine the ORR, PFS, and toxicity for this treatment. Patients must have been administered 1-2 prior cytotoxic regimens. Treatment consisted of bevacizumab (15 mg/kg) IV every 3 weeks until disease progression or prohibitive toxicity. Between April 2002 and August 2004, 64 patients were enrolled, of which 2 were excluded for wrong primary and borderline histology and 62 were evaluable (1 previous regimen=23, 2 previous regimens=39). The median disease free interval from completion of primary cytotoxic chemotherapy to first recurrence was 6.5 months. Early results demonstrated that some patients had confirmed objective responses and PFS in some was at least 6 months. Observed Grade 3 or 4 toxicities included allergy (Grade 3=1), cardiovascular (Grade 3=4; Grade 4=1), gastrointestinal (Grade 3=3), hepatic (Grade 3=1), pain (Grade 3=2), and pulmonary (Grade 4=1). As of 11/04, 36 patients were removed from the trial, including 29 for disease progression and 1 for toxicity in 33 cases reported. Preliminary evidence exists for objective responses to bevacizumab (Burger R, et al, ASCO05, Abs. 5009).An open label, single arm, 2-stage, phase II clinical trial (protocol ID: AVF2949g, NCT00097019) of bevacizumab in patients with platinum resistant, advanced (Stage III or IV), ovarian cancer or primary peritoneal cancer for whom subsequent doxorubicin or topotecan therapy also has failed was initiated in November 2004 at multiple locations in the USA to determine the safety and efficacy for this treatment.A multicenter phase II clinical trial was initiated in April 2002 to determine the 6-month PFS of patients with persistent or recurrent ovarian epithelial or primary peritoneal cancer treated with bevacizumab (protocol ID: GOG-0170D, CDR0000068839, NCT00022659). IV bevacizumab is administered over 30-90 minutes on day 1. Treatment is repeated every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. A total of 22-60 patients will be accrued within 12-30 months. Robert A. Burger, MD, of Chao Family Comprehensive Cancer Center is Trial Chair.This trial was closed in August 2004.

 

 

Sources

http://www.fiercebiotech.com/story/fda-review-red-flags-astrazenecas-case-ovarian-cancer-drug-olaparib/2014-06-23

 

http://www.fiercebiotech.com/story/fda-experts-spurn-astrazenecas-pitch-ovarian-cancer-drug-olaparib/2014-06-25

 

http://www.fiercepharma.com/story/eu-backs-roches-avastin-hard-treat-ovarian-cancer/2014-06-27

 

In a followup to this original posting A Report From the Institute of Medicine of the National Academies of Sciences, Engineering, and Medicine entitled

Evolving Approaches in Research and Care for Ovarian Cancers

was generated in a ViewPoint piece in JAMA which discussed their Congressional mandated report on the State of the Science in Ovarian Cancer Research, titled

Ovarian Cancers: Evolving Paradigms in Research and Care 

highlights some of the research gaps felt by the committee in the current state of ovarian cancer research including:

  • consideration in research protocols of the multitude of histologic and morphologic subtypes of ovarian cancer, including the feeling of the committee that high grade serous OVCA originates from the distal end of the fallopian tube (espoused by Dr. Doubeau and Dr. Christopher Crum) versus originating from the ovarian surface epithelium
  • a call for expanded screening and prevention research with mutimodal screening including CA125 with secondary transvaginal screen
  • better patient education of the risk/benefit of genetic testing including BRCA1/2 as well as in consideration for PARP inhibitor therapy
  • treatments should be standardized and disseminated including more research in health outcomes and decision support for personalized therapy

This Perspective article can be found here: jvp160038

Some other posts relating to OVARIAN CANCER on this site include

Efficacy of Ovariectomy in Presence of BRCA1 vs BRCA2 and the Risk for Ovarian Cancer

Testing for Multiple Genetic Mutations via NGS for Patients: Very Strong Family History of Breast & Ovarian Cancer, Diagnosed at Young Ages, & Negative on BRCA Test

Ultrasound-based Screening for Ovarian Cancer

Dasatinib in Combination With Other Drugs for Advanced, Recurrent Ovarian Cancer

BRCA1 a tumour suppressor in breast and ovarian cancer – functions in transcription, ubiquitination and DNA repair

 

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2013 – Personal Perspectives on Revolutionizing Medicine and Top Stories in Cardiology

Reporter: Aviva Lev-Ari, PhD, RN

Topol Reviews 2013: A Year of Revolutionizing Medicine

 Medscape > Eric Topol on Medscape

Director, Scripps Translational Science Institute; Chief Academic Officer, Scripps Health; Professor of Genomics, The Scripps Research Institute, La Jolla, California; Editor-in-Chief, Medscape

Disclosure: Eric J. Topol, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AltheaDX; Biological Dynamics; Cypher Genomics (Co-founder); Dexcom; Genapsys; Gilead Sciences, Inc.; Portola Pharmaceuticals; Quest Diagnostics; Sotera Wireless; Volcano. Received research grant from: National Institutes of Health; Qualcomm Foundation

December 11, 2013

Practice Changers: Lab Innovations and Genetic Testing

It was almost a year ago that I signed on as Editor-in-Chief of Medscape, and I’m extremely grateful for the opportunity and for the extensive input so many of you have provided. In my last monthly newsletter for the year, I would like to expound on why I think this is the most exciting time ever in the history of medicine and how it will be imminently practice-changing.

Looking at the Laboratory

Let me first turn to laboratories, a big part of how we practice. We send our patients to the clinic or hospital lab, or a central facility, to get their blood drawn. Typically, multiple tubes of blood are obtained; the costs are not transparent; and perhaps even worse, the results are not easily or routinely accessible for most patients. Last month, I highlighted a new entity on the scene — Theranos — and interviewed Elizabeth Holmes, the young CEO.

Theranos will be in all Walgreens stores before long, leveraging microfluidic technology to do hundreds of assays with a droplet of blood, with a fully transparent cost list, and ultimately with results directly going to both the patient and doctor. After 60 years of unchanged laboratory medicine practice, this new, innovative model will help drive disruption — just the kind of shake-up that we have needed.

Second, while touching on labs, recently there has been a big flap between 23andMe, a direct-to-consumer genomics company, and the US Food and Drug Administration (FDA).[1]This was probably attributable to a prolonged lapse of communication on the part of the company, concurrent with aggressive marketing of the product. 23andMe has temporarily stopped providing health-related genetic testing, such as disease susceptibility, carrier state, and pharmacogenomics. Their intention is to work things out with the FDA and get their full $99 panel back up in the months ahead. Why is this an important issue? A Nature editorial[2] posited, “so even if regulators or doctors want to, they will not be able to stand between ordinary people and their DNA for very long.”

Genetic Tests and the “Angelina Effect”

In May of this year, Angelina Jolie published her “My Medical Choice” op-ed,[3] signaling her decision to not only get her BRCA 1,2 genes sequenced but to also undergo bilateral mastectomy.The impact of the so-called “Angelina effect” has been felt worldwide, with a large spike in BRCA testing driven by consumers, and challenges to prevailing cultural norms in places such as Israel, where there is a very high rate of pathogenic BRCA mutations but close to the lowest rate of preventive surgery.[4]

The issue at hand is the availability of genetic tests to patients, which didn’t exist before. Pregnant women can now, in their first trimester, have a single tube of blood drawn to screen for multiple chromosomal aberrations. Amniocentesis is quickly becoming a bygone procedure.[5] The power of genetic testing in practice is just starting to be felt and will be increasingly transformative in the years ahead.

Restructuring and Digitizing Medicine

The Out-of-Hospital Experience

Third, the structural icons of medicine are undergoing reassessment. What do we do with hospitals and clinics in a digital medicine world? George Halvorson, the outgoing CEO of Kaiser Permanente, has weighed in on this by saying that we should start delivering healthcare “farther and farther” from the hospital setting and “even out of doctors’ offices.”[6]

Cisco did a large consumer survey and found that over 70% of patients would prefer a virtual rather than a physical office visit.[7] A tweet that I put out in response to a Fast Company article[8] that said “the idea of going down to your doctor’s office is going to feel as foreign as going to the video store” attracted considerable attention.

Just this week, a large Intel poll of 12,000 consumers found that most believe that hospitals as we know them today will be “obsolete in the near future.”[9] The fact that we are even now questioning what to do with our hospitals and clinics is telling in itself and reflects the profound forthcoming changes in medicine.

Tracking the Human Body 

What Made Medical News in 2013?

Fourth and finally, the explosion of sensors is especially worth noting. This year, the FDA approval of smartphone ECGs and digitized pills heralded the beginning of many more novel digital ways that we will be tracking patients in the future. A watch that passively and continuously captures blood pressure from every heartbeat is just around the corner. We don’t even know what “normal” blood pressure is when it can be assessed 24/7, throughout the night, and during any time of stress, and this is representative of what the era of wireless sensor tracking will bring.

I hope that I have convinced you, with just a few examples, that this is an extraordinary time in medicine. We are all lucky to be a part of it, to see it go through its major reconfiguration and refinement. I will continue to post the links to anything that I think is particularly interesting on a daily basis via Twitter, and you are welcome to follow me @EricTopol.

Wishing you and your family all the best in the New Year. Despite some counterforces, let’s hope that 2014 takes medicine to new heights, with ever more palpable changes and improvements in the way that we render healthcare for our patients.

Eric J. Topol, MD

Editor-in-Chief, Medscape

References

  1. The FDA and thee. The Wall Street Journal. November 25, 2013.http://online.wsj.com/news/articles/SB10001424052702304465604579220003539640102 Accessed December 10, 2013.
  2. The FDA and me. Nature. December 3, 2013. http://www.nature.com/news/the-fda-and-me-1.14289 Accessed December 10, 2013.
  3. Jolie A. My medical choice. The New York Times. May 14, 2013.http://www.nytimes.com/2013/05/14/opinion/my-medical-choice.html Accessed December 10, 2013.
  4. Rabin RC. In Israel, a push to screen for cancer gene leaves many conflicted. The New York Times. November 26, 2013. http://www.nytimes.com/2013/11/27/health/in-israel-a-push-to-screen-for-cancer-gene-leaves-many-conflicted.html Accessed December 10, 2013.
  5. Topol EJ. Topol predicts genomic screening will replace amniocentesis. Medscape. November 11, 2013.http://www.medscape.com/viewarticle/814052 Accessed December 10, 2013.
  6. Friedman B. The future of healthcare: virtual physician visits & bedless hospitals. Lab Soft News. April 1, 2013.http://labsoftnews.typepad.com/lab_soft_news/2013/04/the-future-of-healthcare-less-emphasis-on-hospital-visits.html Accessed December 10, 2013.
  7. Cisco. Cisco study reveals 74 percent of consumers open to virtual doctor visit. March 4, 2013.http://newsroom.cisco.com/release/1148539/Cisco-Study-Reveals-74-Percent-of-Consumers-Open-to-Virtual-Doctor-Visit Accessed December 11, 2013.
  8. Fast Company. Could ePatient networks become the superdoctors of the future?http://www.fastcoexist.com/1680617/could-epatient-networks-become-the-superdoctors-of-the-future
  9. Fisher N. Global study finds majority believe traditional hospitals will be obsolete in the near future. Forbes. December 9, 2013. http://www.forbes.com/sites/theapothecary/2013/12/09/global-study-finds-majority-believe-traditional-hospitals-will-be-obsolete-in-the-near-future/ Accessed December 10, 2013.

SOURCE

http://www.medscape.com/viewarticle/817648_1

John Mandrola’s Top 11 Cardiology Stories of 2013

by John M. Mandrola, MD

Clinical Electrophysiologist, Baptist Medical Associates, Louisville, Kentucky

Disclosure: John M. Mandrola, MD, has disclosed the following relevant financial relationships:
Served as a speaker or member of a speakers bureau for: Biosense/Webster

In Medscape Cardiology, December 20, 2013

 

1. Obamacare/Affordable Care Act

The reforms that sweep in with the tidal waves of Obamacare will transform the landscape of cardiology. Things look differently already, but even more change is coming. Optimism is healthier than pessimism, so my assessment is: Obamacare will be associated with better heart disease outcomes.

Here’s why: What single factor limits improvement of outcomes in heart disease? It’s surely not a lack of access to echocardiograms, or new antiplatelet drugs, or LAA occlusion devices. Rather, it’s the lack of patients’ adherence to healthy lifestyles choices. Cardiologists have reached a therapeutic threshold. Gains in the treatment of heart disease have become and will likely stay incremental. The next big jump in heart disease outcomes will require patients’ actions — not doctors’.

The chief strength of Obamacare is that it ushers in the era of cost-shifting to patients. People will pay more for care. This, I believe, will favor the adoption of healthy lifestyles. Skin in the game, will, on the whole, do great things for heart health. The car analogy: We get our oil changed in our car because preventative maintenance is cost-effective. If you never had to pay for a new car, there’d be little incentive not to trash your current one.

I can hear the naysayers. Placing more of the costs on patients will keep them from getting care. Yes, in isolated cases, which will surely be amplified — this might be true. But overall, 3 arguments refute this thinking: First is that in the past decade, both deaths from heart disease and number of cardiology procedures have declined. Patients are doing better while we do less. Second is the observation that countries that do far fewer procedures boast better CV outcomes. Third, you don’t really believe that doctors control outcomes, do you?

2. The George Bush Stent Case

More than 2 decades ago, a mentor at Indiana taught me that squishing a high-grade coronary lesion did not reduce the risk for heart attack or death. I still remember where I was when I heard that. It was that counterintuitive. The notion that the vulnerable plaque is not the one that looks like a baddie on an angiogram has been proven time and time again. What’s truly remarkable is the resistance of the cardiology community to accept it. Perchance, our visceral reactions to angiograms have clouded our interpretation of science.

Cynics would believe that the overuse of stents — in the face of contrary clinical evidence — is due to financial incentives. They point to examples of outrageous behavior on the part of a tiny few outliers behaving very badly. I can’t deny that incentives don’t play a role, but I think this story has more to do with the cognitive bias stemming from the success of acute primary angioplasty. It’s tempting to merge the stunning benefits of intervening in an acute MI situation to the nonacute situations.

The George Bush story is big because the media attention forced us to look again at the science of the COURAGE trial.[1] What’s more, this story gave strength to those who question the entrenched paradigm of ischemia-guided revascularization. Imagine the implications for cardiology if there was little reason to look for asymptomatic ischemia.

3. Cholesterol Guidelines: Who Decides the “Need” for a Statin?

The cholesterol guidelines[2] had some obvious practice-changing revelations: (1) the end of nonstatin cholesterol-lowering drugs; (2) cessation of treating to numbers; (3) the notion of using statins as cardiovascular risk reducers, rather than cholesterol-lowering drugs; (4) the fight over where CV risk warrants statin intervention.

These are big issues, but I don’t see them as the biggest part of the 2013 cholesterol guideline story. I think what makes this a tipping point in clinical cardiology is the notion that the ultimate decision to take a statin falls with the patient.

Writing to patients in Forbes, Dr. Harlan Krumholz says:

It is your decision. Your doctors can guide you, but you deserve to be informed about the decision and make the choice that feels most comfortable to you. You do not know if you will be the person who avoids a heart attack or will suffer a side effect. You should have the information about what you are likely to gain by taking the medication — and what risks you are incurring. The decision to take the drug should mean that you believe that you are more likely to benefit from the drug than to be harmed by it. And even if a drug has a benefit for you, you have a right to decide whether it is right for you.

This is huge because it brings patient-centered, shared decision-making to the mainstream. Before the cholesterol guidelines, shared decision-making was something you read about in academic journals. But now, across doctors’ offices throughout the United States, low-risk patients will have to decide whether their 1-in-100 chance of preventing a heart attack is worth the 1-in-100 chance of developing diabetes or other statin side effects. Getting patients to see tradeoffs, NNTs, and aligning care with their goals isn’t just a story of 2013; it’s a story of the decade.

JNC-8, Obesity and AF, and NOACs

4. High Blood Pressure Guidelines

I often tell this story to patients: When I was a younger doctor, I would take my 94-year-old grandfather around to see the best doctors in town. We both held to the fantasy that doctors could “fix” him. Mostly he had age-related problems. He did, however, own one shining beacon of good health: He had perfect blood pressure, without medication. My message to patients is that my grandfather lived to 94 because of those BP readings.

What I learned from my grandfather’s case, which has now been borne out in the new JNC 8 guidelines,[3] is that it matters how one achieves good blood pressure. The new guidelines, chaired by a family medicine professor (how cool is that?), continues to disrupt the concept that more drug treatment leads to better outcomes.

It is indeed striking what can be found when one looks carefully and systematically at absolute benefits of treatments from randomized clinical trials. Truthfully, did you know that there was essentially no evidence that treating mild high blood pressure in patients younger than 60 improves outcomes? I didn’t.

Here the affect heuristic looms large. I find great pleasure in the idea that the medical establishment is now poised to embrace common sense. Namely, that modifying a single risk factor with a chemical that surely has multiple system-wide effects does not necessarily improve outcomes.

5. In Electrophysiology, Treat the Underlying Cause of AF

There are a few landmark studies I keep around the exam room for show-and-tell. 2013 brought another keeper. Dr. Prashanthan Sanders and colleagues (from Adelaide, Australia) are authors of the most impactful study in all of cardiology in 2013.[4]

Here is the story: Atrial fibrillation is increasing exponentially. Electrophysiologists see patients at the end of the disease spectrum. Rate control, rhythm control, and anticoagulation are each important treatment strategies, but they don’t address the root cause of AF. In previous work in animal models, this group of researchers showed that obesity increases the susceptibility to AF.

The hypothesis was that weight loss (and aggressive attention to other cardiometabolic risk factors) would reduce AF burden. They randomly assigned patients on their waiting list for AF ablation to 2 groups: (1) a physician-led aggressive program that targeted primarily weight loss, but also hypertension, sleep apnea, glucose control, and alcohol reduction; or (2) standard care with lifestyle counseling.

The findings were striking. Compared with the group of patients receiving standard care, patients in the physician-directed program lost weight, reported less AF symptoms, and had fewer AF episodes recorded. Most impressive were the structural effects noted on echocardiograms. Patients in the intervention group had regression of left ventricular hypertrophy and reduction in left atrial size.

Though this is a small trial, it is practice-changing for cardiology. It shows that treating modifiable risk factors remodels the heart and in so doing reduces the burden of AF. In an interview in JAMA, Dr. Sanders says aggressive risk factor treatment should be a standard of care. I agree. Right now, AF ablation is too often thought of in terms of a supraventricular tachycardia ablation — a fix for a fluke of nature. It’s not that way. In the majority of AF cases, the same excesses that cause atherosclerosis also cause AF. Rather than make 50 burns in the atria, it makes much more sense to address the root cause.

NOACs

6. Novel Anticoagulants Face Value-Based Headwinds

Tell me you haven’t been in this situation: You are making rounds on a patient with newly diagnosed AF, admitted the night before. She has multiple risk factors for stroke. Her heart rate has been controlled and her symptoms improved. There are now 2 choices for anticoagulation: (1) Start warfarin, and while waiting for an adequate INR, cover with IV-heparin (days in hospital) or low-molecular-weight heparin (teaching- and dollar-intensive); or (2) Begin a novel oral anticoagulant (NOAC) and discharge the patient that day. It’s so much easier to use NOAC drugs.

But then what happens when the “starter” kits run out and the patient faces a massive bill at the pharmacy, or her third-party payer denies payment? Now our patient has a problem. She is in AF and has risk factors for stroke. A gap in anticoagulation is not desirable.

At the heart of this issue is the value and superiority of NOAC drugs compared with warfarin. At the 2013 American Heart Association Sessions, the ENGAGE-AF trial showed that the newest NOAC drug, edoxaban, compared favorably to warfarin.[5] All 4 clinical trials of NOAC drugs vs warfarin looked strikingly similar — namely, that in absolute benefits (stroke reduction) and harm (bleeding), NOAC drugs and warfarin performed similarly, within 1% of each other. In the cost-conscious, evidence-based climate of 2013, NOAC drugs are increasingly recognized as overvalued. Warfarin, with all its imperfections, remains steady.

Transparency, End-of-Life Care, and TACT

7. The Sunshine Act

Cardiology is a drug- and device-intensive field. Collaboration with industry is necessary. Skillful use of stents, ICDs, ablation, and pharmaceutical agents has enhanced and saved the lives of millions of patients. Yet, there is clear evidence of overuse and misuse of expensive technology. Look no further than studies that show huge geographic practice variation,[6] which I wrote about here.

The 2013 Sunshine Act has changed the landscape of cardiology education and influence. The upside of transparency is that knowing the financial relationships of investigators is an important part of judging science. Perhaps more important, though, is the possibility that the Sunshine Act will help remove those with financial relationships from guideline writing. Given the influence of guidelines, it’s important that writers be free of conflicts.

The potential downsides of too much Sunshine are noteworthy. After being interviewed in the Wall Street Journal this August,[7] I wrote the following on my blog:

Doctors are a conservative lot. Concern over perception will surely decrease physicians’ interactions with industry, both the useful and not so useful ones. The effect on physician education might suffer. Though the Ben Goldacres of the world rightly emphasize bias when industry entwines itself with medical education, I can attest to have learned a lot from industry-sponsored programs. And this too: one thing that happens when industry sponsors a learning session is that doctors come to it. They talk; they share cases; they come together face-to-face. Such interactions are critical. Will the disappearance of sponsored sessions decrease the amount of face-to-face learning?

We shall soon learn whether all this sunshine enhances health or causes burns.

8. Compassionate Care of the Elderly

Cardiologists are programmed to see death as the enemy. This is a very good thing when treating diseases like STEMI. But a side effect of improving life-prolonging interventions is that patients live long enough to develop other problems. Cardiologists are increasingly asked to treat the elderly and the frail. And this is a challenge because in these patients, treating death as if it’s avoidable is perilous. Delaying death is not the same as prolonging life. Treating a disease is not the same as treating a person.

It’s possible that 2013 will be the year in which things changed for the better in the care of the elderly. And if it is, we will have Katy Butler, an author and investigative journalist, to thank. Ms. Butler’s 2013 book, Knocking on Heaven’s Door, poignantly chronicles the difficulties that both her parents struggled with as they approached the end of life.[8] In both cases, suffering occurred because of disconnect with cardiologists who behaved as if death were optional.

Writing in the Wall Street Journal this September, Ms. Butler describes her mother’s decision to forego aggressive intervention for valvular heart disease.[9] Despite being cared for in one of the nation’s elite heart hospitals, Mrs. Butler’s mother was forced to fight hard for her right to self-determination. Perhaps she mustered the strength to fight for a good death because of the lessons she learned as a caregiver for her chronically ill husband, whose death was tragically prolonged at the hands of paternalistic cardiologists. In Ms. Butler’s father’s case, which she describes in this award-winning New York Times Magazine essay, cardiologists implanted an unnecessary pacemaker and then refused to deactivate it, against the family’s wishes.[10]

As the American College of Cardiology begins an awareness campaign for aortic stenosis, and transcutaneous approaches to valvular disease begin their long road to clinical utility, no topic could be timelier than compassionate patient-centered care for the elderly. 2013 is the year that the oath of Maimonides — “Oh, God, Thou has appointed me to watch over the life and death of Thy creatures” — becomes even more relevant to cardiologists, the guardians of technology.

9. Chelation Therapy

Nothing has become more virtuous in the practice of medicine than clinical evidence. We have set out the rules: The scientific method will determine the best treatments for our patients. One group gets treatment A and the other treatment B. Then we measure outcomes — the simpler the better. These are the rules of the game; they can’t be changed when we don’t like how the game turns.

The TACT investigators have followed the rules. They compared 322 diabetic patients with coronary heart disease who were treated with chelation vs 311 similarly matched patients treated with placebo infusions.[11] The primary endpoint, a composite of death, MI, stroke, revascularization, and hospitalization for angina, occurred in 80 of 322 (25%) treated with chelation and 117 (38%) on placebo. That’s an absolute — not relative — reduction of 13%, and an astounding NNT of 7. For comparison, statin drugs for primary prevention, or NOAC drugs vs warfarin in patients with AF, have NNTs greater than 100.

What makes chelation in diabetics a top story of the year is more than just the data. By the authors’ own account, these findings need to be replicated. What’s really big here is the voracity of opposition from the establishment. I re-read what I said in my opinion piece from November. I’m sticking to it: “It would be a huge mistake to dismiss this science because chelation does not conform to preconceived notions or because it is practiced outside the mainstream of medicine. Let’s not forget about the patients with this terrible disease. It’s not as if we have good treatments for them.”

EMRs and the Blogosphere

10. EMR and the Danger It Poses to the Patient-Doctor Connection

Among Mr. Obama’s broken promises (if you like your insurance plan…) was that the efficiency inherent in electronic medical records (EMRs) would solve the growing cost of healthcare.

In 2013, nearly every doctor is being forced to adopt an EMR. Medicine is replete with examples of good ideas gone awry. There is no better example of this than medical EMR systems. The list is long: EMRs interface poorly with users (doctors). Completing a medical record on an encounter for a common heart rhythm ailment requires me to click more than 25 times. (Fact: EMRs either decrease the number of patients one can see, or worse, they cause a doctor to spend less face time with each patient.) EMRs don’t talk to each other — and in their current form, never will. There is not a shred of evidence that they improve real outcomes. EMRs function more as a billing invoice than a useful medical record.

Doctors are the end-users but not the customers of EMR companies, so our feedback carries little weight. EMR companies effectively answer to no one. And talk about conflict of interest: Anointed EMR companies have become immensely profitable. Even the New York Times took notice.[12]

None of this is the worst part. The worst aspect of EMR systems (in their current form) is that they threaten to remove the humanity from something that at its heart should be human: the patient-doctor connection. In 2013, EMR is one of the many forces that threaten the patient-doctor relationship. If this situation improves in 2014, I’ll report it; but I’m not optimistic. (Full disclosure: I love computers.)

11. Social Media

The American College of Cardiology, the Heart Rhythm Society, the BMJ, and the New England Journal of Medicine are all actively engaged in social media and blogging. I gave a talk at an Indiana University medical student leadership conference this year. Nearly every medical student was on Twitter. So is the president of the ACC and SCAI, as are millions of patients.

The democracy of information on social media enhances patient involvement in medical decision-making. When patients have information, decisions improve. AF patient Mellanie True Hills has made her Website, StopAfib, a go-to resource for patients, a place where influential academic leaders in electrophysiology have taken the time to be interviewed. Social media empowers patient advocates.

Social media is also transforming influence. In the past, the only influencers in cardiology were academic leaders — those who have access to medical journals. That is changing. Look at me: I am a nobody in the academic world, yet Dr. Rich Fogel, the former president of the Heart Rhythm Society (HRS), put me on the same stage with Dr. Douglas Zipes, Dr. Brian Olshansky, and Dr. Anne Curtis at the 2013 HRS sessions to speak about ICDs.

Finally, this is speculative, but I believe that social media has the power to transform medical education. This year, the biggest electrophysiology story from the 2013 European Society of Cardiology Congress was the Echo-CRT trial.[13] This was a practice changer because it put a stop to implanting CRT devices in patients destined to be nonresponders. Dr. Jay Schloss (Christ Hospital, Cincinnati, Ohio), writing on his personal blog, provided clear and useful coverage for free, without the need for registration. Another example: I think IV-diltiazem is overused and misused. In the academic literature, you cannot find a contemporary piece to support this view. But you can on social media.

This is my top 11 for 2013. I invite you to use the comments section to share your top cardiology picks.

 SOURCE

http://www.medscape.com/viewarticle/818115_1

 

 

 

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Genetic Testing for Women at Risk of Cancer

Reporter: Aviva Lev-Ari PhD, RN

Published: May 16, 2013

To the Editor:

Opinion Twitter Logo.

For Op-Ed, follow@nytopinion and to hear from the editorial page editor, Andrew Rosenthal, follow@andyrNYT.

In her thoughtful article about her choice to undergo a double mastectomy, Angelina Jolie said the cost of genetic testing for BRCA1 and BRCA2 mutations “remains an obstacle for many women” (“My Medical Choice,” Op-Ed, May 14).

Our BRACAnalysis test has been used by more than a million women to assess their risk of hereditary breast and ovarian cancer.

The test remains widely reimbursed by insurance companies, with more than 95 percent of at-risk women covered and with an average out-of-pocket cost of about $100. And, thanks to preventive care provisions in the Affordable Care Act, many patients can receive BRACAnalysis testing with no out-of-pocket costs.

For patients in need, Myriad offers a patient assistance program that offers testing at reduced costs or free of charge.

PETER MELDRUM

President and Chief Executive

Myriad Genetics

Salt Lake City, May 16, 2013

To the Editor:

Jolie’s Disclosure of Preventive Mastectomy Highlights Dilemma” (front page, May 15) discusses Angelina Jolie’s decision to undergo prophylactic surgery after testing positive for a BRCA1 mutation. It should be noted that not all hereditary breast and ovarian cancer is attributable to mutations in BRCA1 and BRCA2.

An alternative dilemma exists when a patient has a very strong family history of breast and ovarian cancer, especially diagnosed at young ages, and the BRCA test is negative.

The patient is left wondering what to do next. These patients should consider a new method of testing for multiple genetic mutations via next-generation sequencing, which can often be ordered as part of a research protocol in academic centers.

SUSAN KLUGMAN

Bronx, May 15, 2013

The writer, a clinical geneticist, is director of reproductive genetics at Montefiore Medical Center and an associate professor at Albert Einstein College of Medicine.

 

http://www.nytimes.com/2013/05/17/opinion/genetic-testing-for-women-at-risk-of-cancer.html?src=recg

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