Sunday, April 17, 2016
Bill S-201 Gov't Canada (proposed) Genetic Non-Discrimination Act (subscribe to follow)
Bill S-201 | openparliament.ca
Bill S-201
Genetic Non-Discrimination Act
An Act to prohibit and prevent genetic discrimination
This bill was previously introduced in the 41st Parliament, 2nd Session.Status
First reading (House), as of April 14, 2016
Subscribe to a feed of speeches and votes in the House related to Bill S-201.
Subscribe to a feed of speeches and votes in the House related to Bill S-201.
Summary
This is from the published bill. The Library of Parliament often publishes better independent summaries.
This
enactment prohibits any person from requiring an individual to undergo a
genetic test or disclose the results of a genetic test as a condition
of providing goods or services to, entering into or continuing a
contract or agreement with, or offering specific conditions in a
contract or agreement with, the individual. Exceptions are provided for
health care practitioners and researchers. The enactment provides
individuals with other protections related to genetic testing and test
results.
The enactment amends the Canada Labour Code to protect employees from being required to undergo or to disclose the results of a genetic test, and provides employees with other protections related to genetic testing and test results. It also amends the Canadian Human Rights Act to prohibit discrimination on the ground of genetic characteristics.
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The enactment amends the Canada Labour Code to protect employees from being required to undergo or to disclose the results of a genetic test, and provides employees with other protections related to genetic testing and test results. It also amends the Canadian Human Rights Act to prohibit discrimination on the ground of genetic characteristics.
read less
Elsewhere
All sorts of information on this bill is available at LEGISinfo, provided by the Library of Parliament. You can also read the full text of the bill.
Saturday, April 16, 2016
ICON-6: the danger of changing study design midstream - Comment
The Lancet
Comment
.... Most importantly, we must do everything we can as clinical trialists to reassure the patients and the public that their participation is always considered with the utmost care and constant vigilance around the emerging risk–benefit ratio, and never taken for granted. To get patients to participate in research is already challenging, and we are too permissive of stakeholders changing their minds midstream.....Jonathan Ledermann and colleagues1, 2 report the ICON-6 randomised trial findings for the tyrosine kinase inhibitor cediranib in relapsed platinum-sensitive ovarian cancer. Cediranib offered the prospect of improved efficacy with tolerable side-effects, and ICON-6 was a pragmatic trial to provide real-world evidence of the effectiveness, safety, and acceptability of cediranib plus chemotherapy (either concurrent or concurrent plus maintenance as long as patients were deriving benefit), compared with chemotherapy plus placebo. ICON-6 found ”meaningful improvement in progression free survival”2 (hazard ratio 0·56, 95% CI 0·44–0·72) for concomitant plus maintenance cediranib compared with placebo, as well as significantly more diarrhoea, hypothyroidism, and voice changes. However, after unexpected and major design changes were enforced, we still await data for overall survival; the safety data are less informative than might be necessary, and there are no convincing data yet for patient acceptability and quality of life, which can be particularly relevant to inform trade-offs between improved efficacy and increased side-effects. These design changes should not have been necessary, and clinical trials should be better structured to make sure this does not recur.....
References
- Ledermann J, Perren TJ, Raja FA, et al. Randomised double-blind phase III trial of cediranib (AZD 2171) in relapsed platinum sensitive ovarian cancer: results of the ICON6 trial. European Cancer Congress; Amsterdam, Netherlands; Sept 27–Oct 1, 2013. Abstr 10.
- Ledermann, JA, Embleton, AC, Raja, F..., and on behalf of the ICON6 collaborators. Cediranib in patients with relapsed platinum-sensitive ovarian cancer (ICON6): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016; 387: 1066–1074
Renal cell carcinoma metastatic to the ovary or fallopian tube: a clinicopathological study of 9 cases
abstract
Summary
Renal cell
carcinoma (RCC), the most common type of kidney cancer in adult, rarely
metastasizes to the ovary or fallopian tube, and most cases published
in the literature were case reports. Herein, we describe the
clinicopathological features of 9 cases of RCC metastatic to the ovary
(n = 8) or the fallopian tube (n = 1). The patients' age at the onset of
primary renal tumor was available in 8 patients, ranging from 37 to 73
years (mean, 51 years; median, 50 years). Ovarian metastasis was
detected prior to or concurrently with the primary renal tumors in 3
patients, and after the diagnosis of renal tumors in 6 patients. The
histotypes of the RCCs were clear cell (n = 7), chromophobe (n = 1), and
unclassified (n = 1). Immunohistochemical stainings were performed on
the sections containing metastatic tumors in 4 cases. Interestingly,
pagetoid intraepithelial spread in the tubal mucosa was observed in the
case of RCC metastatic to the fallopian tube. Among the 8 patients with
follow-up data, 5 died of disease and 3 were alive with disease, with a
follow-up period ranging from 3.7 months to 17 years (mean, 77 months;
median, 53 months) after the diagnosis of primary kidney tumors.
Diagnostically, metastatic RCC may mimic primary ovarian tumors
clinically, morphologically, or immunophenotypically. Pathologists
should also keep in mind that both ovarian and kidney tumors express
PAX8 and PAX2, the markers commonly used to diagnose metastatic RCC. In
addition, chromophobe RCC only rarely metastasizes, but it can be a
diagnostic challenge when it metastasizes to the ovary.
A prospective evaluation of early detection biomarkers for ovarian cancer in EPIC cohort - open access
full.pdf
April 8, 2016
.... Within the first 12 months after blood donation, for all markers except CA15.3 the ability to predict future cancer diagnosis was clearly stronger for advanced tumors (stage II and III/IV) and relatively weak for stage I tumors (Supplementary Figure 1), and this heterogeneity was statistically significant for CA125 and HE4 (phet < 0.05; Table 2). Regarding tumor histology, CA125, HE4 and CA72.4 showed fairly strong discrimination of serous ovarian cancer patients from their matched controls, especially within short lag-times after blood donation (Supplementary Table S2); for the other histologic subtypes, the numbers of patients were too small to obtain reliable estimates.....Discussion
In our evaluation of four potential ovarian cancer screening biomarkers measured in prospectively collected samples from women with ovarian cancer and matched controls in the EPIC cohort, we observed the best sensitivity and specificity for CA125, followed by HE4, CA72.4, and finally CA15.3. The ability of these biomarkers to distinguish cases from controls declined with increasing time between blood draw and diagnosis, as well as with earlier stage at diagnosis. These observations suggest that, generally, these markers are best at identifying advanced disease close to diagnosis, but their ability to detect early disease that is amenable to interventions that can improve survival may be limited. Addition of a previously established risk prediction model did not improve the performance of markers in women who went on to develop clinically manifest ovarian cancer less than three years in advance of diagnosis. By contrast, adding CA125 (but not CA15.3) to the risk prediction model did slightly improve the longer-term
prediction of ovarian cancer occurrence over a time interval of about 3 to 6 years after blood donation.....
(Results) Combining CA125 with HE4 and further markers modestly improved discrimination. Our study confirms CA125 as the single best marker for the early detection of invasive epithelial ovarian cancer.
Ovarian Cancer and Us (blog) top views this week/by page and country
http://ovariancancerandus.blogspot.com/feeds/posts/default
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When are clinical trials registered? An analysis of prospective versus retrospective registration
Full Text
Conclusions
Despite
the requirement for prospective registration of clinical trials in many
journals for the past ten years, this study is the first to show that a
large number of clinical trials were not prospectively registered.
The
lack of prospective registration identified in this study demonstrates
that more needs to be done to improve adherence to prospective
registration. It also highlights the importance of allowing
retrospective trial registration of studies that have not been
prospectively registered in order to prevent the non-publication of
potentially valuable research for which human participants have given up
their time and exposed themselves to risk.
The
results also suggest that there is a need for clear linkage of
published articles reporting clinical trials to their trial registry
records. This, along with the transparent inclusion of the date of
registration in the published article and clear indication in the trial
registry record when a trial has been registered retrospectively, will
increase transparency and ensure that readers are aware of whether a
clinical trial has been prospectively or retrospectively registered.
Irregular menses predicts ovarian cancer: Prospective evidence from the Child Health and Development Studies
abstract
We tested the hypothesis that irregular
menstruation predicts lower risk for ovarian cancer, possibly due to
less frequent ovulation.
We conducted a
50-year prospective study of 15,528 mothers in the Child Health and
Development Studies cohort recruited from the Kaiser Foundation Health
Plan from 1959-1966. Irregular menstruation was classified via medical
record and self-report at age 26. We identified 116 cases and 84 deaths
due to ovarian cancer through 2011 via linkage to the California Cancer
Registry and Vital Statistics.
Contrary to
expectation, women with irregular menstrual cycles had a higher risk of
ovarian cancer incidence and mortality over the 50-year follow-up.
Associations increased with age (p <0.05). We observed a 2-fold
increased incidence and mortality by age 70 (95% Confidence Interval
(CI) = 1.1, 3.4) rising to a 3-fold increase by age 77 (95% CI = 1.5,
6.7 for incidence; 95% CI = 1.4, 5.9 for mortality). We also found a
3-fold higher risk of mortality for high-grade serous tumors (95% CI =
1.3, 7.6) that did not vary by age.
This
is the first prospective study to show an association between irregular
menstruation and ovarian cancer – we unexpectedly found higher risk for
women with irregular cycles. These women are easy to identify and many
may have polycystic ovarian syndrome. Classifying high-risk phenotypes
such as irregular menstruation creates opportunities to find novel early
biomarkers, refine clinical screening protocols and potentially develop
new risk reduction strategies. These efforts can lead to earlier
detection and better survival for ovarian cancer.
Update on Imaging of Ovarian Cancer (imaging/overview/open access)
open access
...This review will focus on the most common cancer type, epithelial ovarian cancer (EOC). The other primaries including germ cell and sex-cord stromal cell ovarian cancer are extremely rare (<5 %) and differ in many aspects, but share the same staging classification with EOC [5, 6]. An update of recent advances regarding EOC will be provided with special emphasis on their impact on clinical radiological practice.New Insights in Ovarian Cancer Biology
The concept of ovarian cancer as a single disease has been revised. Epithelial ovarian cancer is now understood as a subsumption of diverse cancer entities that vary significantly clinically as well as pathologically and on a molecular level [7–9]. It comprises the following main cancer subtypes:Differentiation of these subtypes is pivotal with regards to several aspects, such as biomarkers, precursor lesions, clinical presentation at diagnosis, prognosis, and response to treatment [5–11] (Table 1). Furthermore, considerable heterogeneity even within the same epithelial ovarian cancer subtype has been identified on a macroscopic and molecular level. This has also been attributed to the dedifferentiation within different implants of the same primary and thus the problem of tumor recurrence after initial response to therapy [3, 12].....
Outcome of genetic evaluation of patients with kidney cancer referred for suspected hereditary cancer syndromes (Lynch syndrome....)
abstract
Highlights
- •
- We identified several factors that may predict positive test results in patients with kidney cancer undergoing evaluation in a clinical genetics clinic. Although these risk factors have previously been associated with cancer syndromes, a need for studies of testing practices remains.
- •
- Our data suggest that in patients with kidney cancer evaluated for hereditary cancer syndromes, young age is associated with diagnosis of RCC syndromes, whereas syndromic manifestations and multiple primaries are found in Lynch syndrome.
- •
- These results, along with clinical pathway, suggested for evaluating patients with kidney cancer for inherited cancer syndrome may be useful for practicing urologists to select patients with kidney cancer to refer for genetic counseling.
Objective
To
analyze patients with kidney cancer referred for evaluation at a
high-volume genetics service at a comprehensive cancer center and
identify factors associated with positive tests for hereditary cancer
syndromes.
Methods
A
retrospective review of patients referred to the Clinical Genetics
Service at Memorial Sloan-Kettering Cancer Center was performed, and
patients with a personal history of kidney cancer were identified.
Patient and disease characteristics were reviewed. In all, 4 variables
including age at diagnosis of kidney tumor, presence of syndromic
manifestations, family history of kidney cancer, and number of primary
malignancies were evaluated for association with positive test results
in 2 groups: patients tested for renal cell carcinoma syndromes and
Lynch syndrome. Guidance for genetic testing strategy in patients with
kidney cancer is provided.
Results
Between
1999 and 2012, 120 patients with a history of kidney cancer were
evaluated by the Clinical Genetics Service. The mean age at kidney
cancer diagnosis was 52 years (interquartile range: 42–63), with 57%
being women. A family history of kidney cancer was reported by 39
patients (33%). Time between diagnosis of first cancer and genetic
consultation was <1 year in 54%, 2 to 5 years in 23%, and>5 years
in the remaining 23%. Overall, 95 patients were tested for genetic
abnormalities with 27 (28%) testing positive. Testing for renal cell
carcinoma (RCC)-related syndromes was performed on 43 patients, with 13
testing positive (30%). Lynch syndrome testing was positive in 9
patients (32%) after 28 were tested. In RCC-associated syndromes, young
age of diagnosis was associated with positive test results. Conversely,
syndromic manifestations and increasing number of primary malignancies
were associated with positive Lynch testing.
Conclusions
The
discovery of inherited kidney cancer syndromes has provided a unique
opportunity to identify patients at increased risk for cancer. Factors
associated with positive genetic testing are unique to different
syndromes. These data suggest that in kidney cancer patients evaluated
for hereditary cancer syndromes, young age is associated with diagnosis
of RCC syndromes, whereas syndromic manifestations and multiple
primaries are found in Lynch syndrome. These results, along with
clinical awareness, may be useful for practicing urologists to select
patients with kidney cancer to refer for genetic counseling.
Ovarian Cancer in Hereditary Cancer Susceptibility Syndromes (BRCA/Lynch Syndrome)
abstract
Hereditary breast and ovarian cancer (HBOC) syndrome and Lynch syndrome (LS) are associated with increased risk of developing ovarian carcinoma. Patients with HBOC have a lifetime risk of up to 50% of developing high-grade serous carcinoma of tube or ovary; patients with LS have a 10% lifetime risk of developing endometrioid or clear cell carcinoma of the ovary. Testing all patients with tubo-ovarian high-grade serous carcinoma for mutations associated with HBOC syndrome, and all patients presenting with endometrioid or clear cell carcinoma of the ovary for mutations associated with LS can identify patients with undiagnosed underlying hereditary cancer susceptibility syndromes.
Laparoscopic fertility-sparing surgery for early ovarian epithelial cancer: A multi-institutional experience
abstract
Highlights
- •
- Laparoscopic fertility-sparing treatment of early ovarian cancer shows encouraging survival outcomes.
- •
- After conservative treatment, 64.8% woman reported pregnancy intent and 60% of these conceived spontaneously.
Objective
There
is as yet limited evidence about fertility-sparing surgery for early
ovarian cancer (EOC) carried out laparoscopically. We sought to
investigate the safety, adequacy and fertility outcome of ovarian cancer
patients who underwent fertility-saving laparoscopic surgical staging
using a multi-institutional sample.
Methods
Prospectively
collected data in five gynecologic oncology service databases were
searched for epithelial EOC patients undergoing laparoscopic
fertility-preserving surgery. Surgical, pathologic, oncologic and
reproductive outcome data were analysed.
Results
The
study cohort consisted of 65 women. Median age of the patients was 33
(range: 21–42) years. In this cohort 36 (55.4%) and 29 (44.6%) patients
were at low risk (FIGO stage IA G1–2) and high-risk (FIGO stage IA G3 or
more), respectively. The disease was reclassified to a higher stage in 4
(6.1%) women. After a median follow up period of 38 months (range:
2–144), the overall survival was 95.4% and recurrence-free survival
84.6%. Overall, there were 23 pregnancies in 22 women. After ovarian
cancer treatment, 64.8% women reported pregnancy intent and 60% of these
conceived spontaneously.
Conclusions
Laparoscopic
staging may represent a viable option for premenopausal women seeking
fertility preservation in the setting of early ovarian cancer. More
research is needed to determine whether laparoscopy may offer
reproductive benefits to this particular population.
The significance and therapeutic potential of PD-1 and its ligands in ovarian cancer: A systematic review
abstract
Highlights
- •
- Ovarian cancer is one of the most common malignant tumors in women.
- •
- The emerging immunotherapy represents a rational approach for cancer treatment.
- •
- Immunotherapy may play a significant role in clinical management of ovarian cancer.
Surgery,
radiotherapy and chemotherapy are the mainstay of malignant cancer
treatments. However, with the development of immunology, the emerging
immunotherapy represents a rational and alternative approach for the
treatment of human cancer, including ovarian cancer (OC). Based on a
body of evidence and the clinical success of immunotherapy in many
malignancies, it is confirmed that blocking the programmed death 1
(PD-1) and its ligands in OC is feasible and valid both in animal models
and patients. Immunotherapy may play a significant role in the future
clinical management and improve the prognosis of OC. This review will
focus on the biological functions, treatment response, toxicity and
viable target of PD-1 and its ligands in OC. Recognition of the multiple
functions of PD-1 and its ligands in ovarian cancer will serve to
deepen our understanding of the nature of OC, develop novel
immunotherapy approaches and discover possible diagnostic and prognostic
biomarkers in future clinical decisions.
Abbreviations
- aa, amino acid;
- Bcl-2, B-cell leukemia 2;
- CTLA-4, cytotoxic T-lymphocyte antigen 4;
- DC, dendritic cell;
- EMA, Europe Medicine Agency;
- FDA, Food and Drug Administration;
- GITR, glucocorticoid-induced TNFR related protein;
- Ig, immunoglobulin;
- ITIM, immunoreceptor tyrosine-based inhibitory motif;
- ITSM, immunoreceptor tyrosine-based switch motif;
- mAb, monoclonal antibodies;
- NK, natural killer;
- NSCLC, non-small cell lung cancer;
- OC, ovarian cancer;
- ORR, overall response rate;
- PFS, progression-free survival;
- PLDH, pegylated liposomal doxorubicin hydrochloride;
- TIL, tumor-infiltrating lymphocyte
Rare non-epithelial ovarian neoplasms: Pathology, genetics and treatmen
abstract
Rare non-epithelial ovarian neoplasms have posed management challenges for many years. Their rarity means that most specialist practitioners will see one such case every several years, and most generalists may never see a case. The first step in management is to establish the correct diagnosis and this may necessitate specialist pathology review. Here, we review recent developments in the pathology, genetics and treatment of small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) and sex cord-stromal tumours. Pathologically, these tumours often display morphological overlap with other neoplasms; for example, SCCOHT overlaps with many other "small round blue cell" tumours. Specific immunohistochemical stains, while useful, may not always be definitive. The discovery of somatic mutations in FOXL2 (adult granulosa cell tumours) and germline and somatic mutations in DICER1 (Sertoli-Leydig cell tumours) and SMARCA4 (SCCOHT) has demonstrated the value of molecular investigation as an adjunct to traditional histopathological approaches. In addition, the presence of germline mutations in a significant proportion of some of these neoplasms points to the need for genetic counselling and testing, offering the prospect of prevention and early diagnosis. Treatment of these rare tumours, as a group, should be on the basis of sound oncological principles, given that level 1 evidence will almost always be lacking. The rationale for experimental therapies must be clearly established. In view of the complex issues involved in the management of these conditions, expert opinion in pathology, genetics and treatment may be essential to offer the patient and her family the best chance of a good outcome.
Level I: Evidence obtained from at least one properly designed randomized controlled trial
Friday, April 15, 2016
(UK) Opinion: Don't tell cancer patients what they could be doing to cure themselves
Opinion + comments
March 26, 2016
If you’re a religious person, for the love of God, don’t tell someone with cancer that if they’d just drink juice (or take vitamins, or pray or have a “positive attitude”) that they could cure themselves.
And if you’re not a religious person, for the love of reason and decency, don’t tell someone with cancer any of these things, either.....
Genetic discrimination lawsuit raises broader concerns about testing, privacy (no abstract/newborn testing)
requires $$ to view - no abstract
Genetic discrimination lawsuit raises broader concerns about testing, privacy
Case involves middle school student impacted by results of genetic screening test as newborn
Cataloging antineoplastic agents according to their effectiveness against platinum-resistant and platinum-sensitive ovarian carcinoma cell lines. - PubMed - NCBI
Cataloging antineoplastic agents according to their effectiveness against platinum-resistant and platinum-sensitive ovarian carcinoma cell lines
Although epithelial ovarian cancers (EOCs) are initially treated with platinum-based chemotherapy, EOCs vary in platinum responsiveness. Cataloging antineoplastic agents according to their effectiveness against platinum-resistant and platinum-sensitive EOC cell lines is valuable for development of therapeutic strategies to avoid platinum inefficacy and to exploit platinum sensitivity. TOV-21G devoid of FANCF expression, OV-90 and SKOV-3 were employed as examples of platinum-sensitive, platinum-intermediate and platinum-resistant cell lines, respectively. Antineoplastic agents examined included mitomycin C, doxorubicin, etoposide, gemcitabine, chlorambucil, paclitaxel, triapine and X-rays. Their effectiveness against cell lines was analyzed by clonogenic assays. Cytotoxic profiles of mitomycin C and carboplatin were similar, with mitomycin C exhibiting greater potency and selectivity against TOV-21G than carboplatin. Cytotoxic profiles of doxorubicin, etoposide and X-rays overlapped with that of carboplatin, while OV-90 overexpressing Rad51 was more resistant to chlorambucil than SKOV-3. The efficacy of paclitaxel and triapine was independent of platinum sensitivity or resistance. Consistent with these cytotoxic profiles, cisplatin/mitomycin C, triapine, and paclitaxel differed in the capacity to induce phosphorylation of H2AX, and produced unique inhibitory patterns of DNA/RNA syntheses in HL-60 human leukemia cells. Paclitaxel and triapine in combination produced additive antitumor effects in M109 murine lung carcinoma. In conclusion, mitomycin C is potentially more effective against Fanconi anemia pathway-deficient EOCs than carboplatin. Doxorubicin and etoposide, because of their overlapping cytotoxic properties with carboplatin, are unlikely to be efficacious against platinum-refractory EOCs. Paclitaxel and triapine are effective regardless of platinum sensitivity status, and promising in combination for both platinum-sensitive and platinum-refractory EOCs.
BRCA Exchange - searchable database BRCA 1/2 variants
BRCA Exchange
Just
type in box above and use auto-complete to search for BRCA1 or BRCA2
variants. For more information about the BRCA1 and BRCA2 genes, genetic
variation, and cancer, please click the About link at the top of the page.
This website is supported by the BRCA Exchange of the Global Alliance for Genomics and Health. The BRCA Exchange advances our understanding of the genetic basis of breast cancer, ovarian cancer and other diseases by pooling data on BRCA1/2 genetic variants and corresponding clinical data from around the world.
This website is supported by the BRCA Exchange of the Global Alliance for Genomics and Health. The BRCA Exchange advances our understanding of the genetic basis of breast cancer, ovarian cancer and other diseases by pooling data on BRCA1/2 genetic variants and corresponding clinical data from around the world.
Intensive breast screening in BRCA2 mutation carriers is associated with reduced breast cancer specific and all cause mortality | Hereditary Cancer in Clinical Practice | Full Text
open access
Discussion
Although
there is evidence for a projected improvement in survival from annual
mammography screening in familial breast cancer (from those largely at
low risk of BRCA1/2) under 50 years of age [17, 18], this is the first time that a prospectively observed reasonably large series of BRCA2
carriers has been shown to have an apparent survival advantage from
annual screening. Recently a Dutch group showed no improvement in
survival, based on only two deaths out of 18 BRCA2 related breast cancers compared to three events in controls [19]. Nonetheless the same group reported that annual mammography screening beyond 60 years of age in BRCA1/2
carriers is associated with a marked improvement in tumour stage at
diagnosis, with 58 % diagnosed at stage two or above with usual
two-yearly screening compared to only 21 % in the annual group [20].
Additionally, the interval cancer rate was doubled by extending
screening to two years. The data from this and the present study concur
with NICE guidelines in England and Wales who recommend annual
mammography for BRCA1/2 carriers until 70 years of age [21]. Although the present study has used a pragmatic comparison group of BRCA2
carriers not undergoing intensive screening a true matched control
series would be impossible as women who knew they were mutation carriers
would be very unlikely to not undergo added surveillance.
The current situation is that no single centre has a series large enough
and well enough constructed and documented to provide a definitive
answer to the question of whether MRI breast screening improves survival
in BRCA2 mutation
carriers. This is why close to all major organisations world-wide
addressing these questions have organised ‘THE BRCA CHALLENGE’ (http://www.humanvariomeproject.org/brca-challenge.html)
which at the 2015 meeting in the UNESCO centre in Paris called for a
broad international collaboration to provide answers to the unanswered
questions. In this context we report our findings and encourage others
to do the same, so as to move our knowledge on effects of interventions
to prevent BRCA2-associated
breast cancer death from assumptions to empirical observed effects of
interventions. Until the time when more definitive answers are available
female BRCA2 carriers will
still require guidance on whether surveillance with MRI and mammography
offers similar improvements in life expectancy than can be gained from
risk reducing surgery [13, 22].
OpenTrials: what, why and how? - blog
On Medicine
14 Apr 2016
We’ve recently published a paper in the journal Trials on something we’re building right now. It’s an ambitious idea, and long overdue: OpenTrials, an open, freely accessible index of all publicly accessible documents and data ever made available, on all clinical trials ever conducted.
The messy world of clinical trials
You might find it surprising that such a thing doesn’t already exist. But the world of clinical trials is currently in something of a mess, as is increasingly recognized, especially when it comes to knowledge management.....(BioMed) OpenTrials: towards a collaborative open database of all available information on all clinical trials
.....The presentation for patients (Fig. 2) is limited by the quality of the data currently available for this audience, but it has significant potential with greater user engagement. For example, we can present search options for ongoing trials for a given condition or a given drug, covering a given geographical area, filtered if necessary for an individual’s eligibility by comparing their entered demographic information against structured data on the inclusion and exclusion criteria of each trial, where data quality permits. Previous efforts to do this have been hindered by the variably poor quality of information on registries for non-specialist users. Here there are many opportunities. The first is from record linkage. For example, all trials must pass through an ethics committee, and all ethics committees require a lay summary. Where we can match the lay summary from ethics committee paperwork, we can present it on the patient-facing page. The second opportunity comes from using the option of crowd-sourcing and annotation, as we can also permit others to upload their own lay summaries. To this end, we have begun negotiating with science communication course leaders to work with them on using this as an exercise for their students, and are also keen that methodological shortcomings in ongoing and completed trials be communicated clearly to patients, with a view to developing a good trials guide. Here, as with other additional features to the core service, our efforts will be driven by opportunities for collaboration.Scientist identifies mechanism underlying peripheral neuropathy
Sciencenews
Scientist identifies mechanism underlying peripheral neuropathy
Discovery raises prospect of treatments for common painful condition Date: April 14, 2016
Rieger conducted her research in zebrafish exposed to paclitaxel, a chemotherapeutic agent used for ovarian, breast, lung, pancreatic and other cancers. Paclitaxel-induced peripheral neuropathy affects the majority of treated patients; however, those who are most severely affected (about 30 percent) have to terminate chemotherapy or reduce the dose because of this condition, which can impact cancer survival.
Journal Reference:
- Thomas S. Lisse, Leah J. Middleton, Adriana D. Pellegrini, Paige B. Martin, Emily L. Spaulding, Olivia Lopes, Elizabeth A. Brochu, Erin V. Carter, Ashley Waldron, Sandra Rieger. Paclitaxel-induced epithelial damage and ectopic MMP-13 expression promotes neurotoxicity in zebrafish. Proceedings of the National Academy of Sciences, 2016; 113 (15): E2189 DOI: 10.1073/pnas.1525096113
The effects of distress and the dimensions of coping strategies on physicians’ satisfaction with competence
open access
Objectives: The purposes of this study were to (1) articulate the dimensions of Coping strategies used by physicians, and (2) determine whether Coping strategies alleviated Distress and enhanced Satisfaction with Competence.
Inherited Mutations in Women With Ovarian Carcinoma
JAMA Network
Conclusions and Relevance Of 1915 patients with OC, 347 (18%) carried pathogenic germline mutations in genes associated with OC risk. PALB2 and BARD1 are suspected OC genes and together with established OC genes (BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, MSH2, MLH1, PMS2, and MSH6) bring the total number of genes suspected to cause hereditary OC to 11.
Risk-averse assisted-death law fails Canadians who are suffering + comments
The Globe and Mail
The best that can be said about Bill C-14 (medical assistance in dying) is that it deserves to be graded “incomplete” in fat red marker.
If there’s one thing that we’ve learned from the seemingly endless right-to-die debate, it’s that the courts are not the place where deeply personal medical choices such as hastened death should be arbitrated.Rather, these decisions should be made solemnly between a patient and a health-care provider and, for the most part, legislators should get the hell out of the way.
Thursday, April 14, 2016
Letter: Why do we pay for information that we won't use ? DTCA
European Journal of Human Genetics
Why do we pay for information that we won’t use? A cognitive-based explanation for genetic information seeking
5 questions for Sean Parker on cancer research - blog
blog
April 13, 2016
Tech entrepreneur Sean Parker is just the latest big name to put up big money to fight cancer.
Parker, who helped found Facebook and Napster, plans to spend $250 million to build teams of researchers who aim to harness the immune system to attack cancer.
That’s on top of the $100 million for cancer immunotherapy research put up by former New York City Mayor Michael Bloomberg and clothing magnate Sidney Kimmel. Biotech billionaire Patrick Soon-Shiong has also assembled a coalition of rival drug companies to focus on immunotherapy. And the White House is proposing spending $755 million on a cancer “moonshot” led by Vice President Joe Biden.....
Surgeons should tell patients of double-booked surgeries, new guidelines say - The Boston Globe
The Boston Globe
April 13, 2016
The world’s largest surgeons’ organization has issued its first-ever guidelines for surgeons managing simultaneous operations, saying the controversial practice is broadly permissible, within limits, but that “the patient needs to be informed” whenever a doctor runs more than one operating room at a time.
Such notice to patients is not now routine or required at many hospitals. The new standards from the American College of Surgeons, issued Wednesday, also aim to bar surgeons from handling cases in which the “critical or key” parts of surgeries overlap.
“A primary attending surgeon’s involvement in concurrent or simultaneous surgeries on two different patients in two different rooms is not appropriate,” the guidelines state.....
Wednesday, April 13, 2016
Stand Up To Cancer - International
Stand Up To Cancer
International Reach
Stand Up To Cancer began in the United States and is now international in scope, with active partnerships managed by the AACR in the United Kingdom, the Netherlands, and Canada. Scientists in many other countries are also involved in research funded by the Stand Up To Cancer program.
(Stand Up to Cancer) Charity Starts Industry-Backed Cancer Research Effort | Science and Enterprise
Sciencenews
13 April 2016.
The charitable group Stand Up to Cancer
unveiled today
a new program to spur research on cancer treatments begun by
pharmaceutical companies. The program known as Catalyst
will harness funds and products from participating companies that will
be bid out to the research community at large for further research and
development.Charter members of Catalyst include the pharmaceutical companies Merck, Bristol-Myers Squibb, and Roche, through its biotechnology subsidiary Genentech. The companies will provide cancer treatments under development, or currently approved drugs for study to treat other disorders, as well as diagnostic or medical devices. Financial or in-kind commitments from these companies for Catalyst were not disclosed.
The Catalyst program itself will be administered by American Association for Cancer Research. Based on participants’ donations, American Association for Cancer Research will issue a request-for-proposal for translational researchers to respond with novel ideas leading to drugs or devices for detecting, preventing, or treating cancer. The request will outline the compounds and other materials provided by the companies, research priorities, estimated number of projects supported, and funds available.
Proposals are expected to follow Stand Up to Cancer’s collaborative model that puts together teams that cross industry and sector boundaries. This team approach, says the organization, brought together 1,100 researchers at 131 institutions, as well as 69 pharmaceutical, biotech, and diagnostics companies. The teams so far produced more than 160 clinical trials planned, underway, or completed.
Sung Poblete, president and CEO of Stand Up to Cancer (SU2C), says Catalyst aims to speed up the rate at which new treatments are being developed. “The Catalyst program,” says Poblete in an organization statement, “is a perfect fit with the SU2C mission of accelerating the pace of groundbreaking translational research that provides new therapies to patients quickly. This will be a nimble program that will help speed up the rate at which we discover what works.”
The Catalyst program will be supervised by an executive board chaired by Phillip Sharp, professor of cancer research at MIT and 1993 Nobel laureate, who also chairs Stand Up to Cancer’s scientific advisory committee. A steering committee of academic and industry representatives will review proposals and recommend awardees.
Stand Up to Cancer, in Los Angeles, is an initiative of Entertainment Industry Foundation. The charity was formed in 2008 by film and media executives who use the industry’s resources to encourage a more collaborative model for cancer research.
From tokenism to empowerment: progressing patient and public involvement in healthcare improvement
open access
Some healthcare professionals and organisations have not embraced the idea of partnership with patients and even feel threatened by the notion of active involvement.10 ,17
The mouse: the scientist's best friend - a couple of interesting items
Medical News
eg.
Perhaps most surprising is the recent revelation that the outcomes of mouse trials can be confounded by the sex of the researchers. A study by researchers at McGill University in Montreal, Canada, claimed to confirm what some anecdotal evidence had suggested - that lab mice and rats become stressed in the presence of male - but not female - researchers, which could distort findings.
Nearly three-quarters of Ontario women hold incorrect belief that a Pap test detects sexually-transmitted infections (ref: ovarian)
Blogger's Note: focus is not specific to ovarian cancer but highlights ongoing misunderstandings
press release
TORONTO, April 11, 2016 /CNW/ - Nearly three-quarters (74 per cent) of Ontario
women incorrectly believe a Pap test detects sexually-transmitted
infections and almost half (48 per cent) believe a Pap test screens for
vaginal cancer, shows a new survey commissioned by Cancer Care Ontario. .....
A
Pap test is a simple screening test that can help prevent cervical
cancer. Women aged 21 to 69 should get screened for cancer with a Pap
test every three years if they are or have ever been sexually active.
The test looks for abnormal cervical cell changes, but it does not test
for other cancers in the reproductive organs, such as ovarian cancer, or
for sexually-transmitted infections, such as chlamydia, gonorrhea or
human immunodeficiency virus (HIV). A Pap test can be done at your
family doctor's office, and if you don't have a doctor, you can get a
test done at a walk-in clinic or sexual health clinic.
Key survey findings:
- Of the 90 per cent of women who said a Pap test screens for cancer, nearly one-half (48 per cent) incorrectly believe it tests for vaginal cancer. More than one-third believe it tests for ovarian cancer (37 per cent) and uterine cancer (34 per cent).
(2015) Impact on Survival With Adjuvant Radiation Therapy for Clear Cell, Mucinous, and Endometriod Ovarian Cancer (SEER)
Blogger's Note: this abstract does not indicate what form of RT (eg. targeted/WAR); it also does not discuss longterm side effects/complications/adverse effects (eg. vs OS)
abstract:
Impact on Survival With Adjuvant Radiation Therapy for Clear Cell, Mucinous, and Endometriod Ovarian Cancer: The SEER Experience From 2004 to 2011 - International Journal of Radiation Oncology • Biology • Physics
Purpose/Objective(s)
To
evaluate the impact of radiation therapy (RT) on cause-specific and
overall survival for stage I-III clear cell, mucinous, and endometrial
ovarian cancer.
Materials/Methods
We
analyzed incidence, survival, and treatment data from the Surveillance,
Epidemiology, and End Results (SEER) Program from 2004 to 2011 for
clear cell, mucinous, and endometrial histologies of the ovary for
stages I-III. We examined cause-specific survival (CSS) and overall
survival (OS) for all 3 histologies combined and for each histology with
relation to the use of adjuvant RT. Survival analysis was calculated by
Kaplan-Meier and log-rank analysis.
Results
There
was a total of 13,313 cases of which 13,024 received no RT and 289
received RT. CSS was higher in individuals who did not receive RT at 5
years (81% vs 74%) and 10 years (74% vs 65%), P=.003. Similarly, OS was higher in individuals who did not receive RT at 5 years (76% vs 73%) and 10 years (64% vs 59%), P=.04. However, stage III patients who received RT had a higher OS at 5- (54% vs 44%) and 10-year intervals (36% vs 30%), P=.04.
For clear cell histology, there were a total of 3467 cases of which 68
received RT. OS was higher in individuals who received no RT compared to
those who received RT both at 5 years (71% vs 41%) and 10 years (61% vs
40%), P<.0001. For mucinous histology, there were a total
of 4369 cases of which 68 received RT. OS was higher in individuals who
received no RT at 5 years (76% vs 70%) and 10 years (65% vs 49%), P=.037.
In contrast, stage III patients with mucinous histology who received RT
had a higher OS at 5- (50% vs 36%) and 10-year intervals (45% vs 26%), P<.05.
For endometriod histology, there were a total of 7993 cases of which
314 received RT. OS was similar in these patients regardless of their RT
status at 5 years (78% vs 81%) and similar at 10 years (65% vs 65%), P=.97.
Conclusion
Over
2004 to 2011, only 2% of all clear cell, endometriod, and mucinous
ovarian cancer cases were treated with adjuvant RT. Those treated with
RT had a lower CSS and OS at 5-year and 10-year intervals. However,
further subgroup analysis revealed a benefit of RT in terms of OS for
all stage III patients and for stage III patients with mucinous
histology. These findings together with previous studies that
demonstrated a potential survival benefit of adjuvant RT for stage I and
II patients in these histologies suggest a role of RT. Therefore,
further investigation should be performed in the indication for RT, dose
and volume treated, RT techniques and delivery, treatment compliance,
and the patient’s functional status for non-metastatic clear cell,
mucinous, and endometriod ovarian cancer.
Cancer Centers Join Intel’s Collaborative Cancer Cloud (Dana-Farber/Ontario Institute for Cancer Research)
sciencenews
wo more cancer centers have joined Intel's Collaborative Cancer Cloud data sharing and research platform, the chip maker and the Oregon Health & Science University (OHSU) have announced.
The platform aims to make it “easier, faster and more affordable for developers, researchers and clinicians to determine how hundreds, even thousands of genes interact to drive disease in individual patients,” according to an OHSU news release. The platform will coordinate the storage, networking, data security, and advanced analytics of participating cancer centers’ pooled data.
The effort will allow individual cancer centers to expand on their own genomics “big data” efforts by pooling data with those of other large institutions.....
Many Clinical Trial Protocol Changes Avoidable, Costly
Sciencenews
12 April 2016. When clinical trials make changes in plans, known as protocol amendments, after they’re underway, the impact in time and costs are substantial, with many changes considered avoidable. These are conclusions of a review of clinical trial protocol amendments carried out by Center for the Study of Drug Development at Tufts University in Boston and the clinical research technology company Medidata Solutions, published recently in the journal Therapeutic Innovation and Regulatory Science (paid subscription required).
Clinical trials for testing pharmaceuticals and medical devices are often complex undertakings, even at early stages with smaller numbers of participants. Kenneth Getz, who studies clinical trial management at Tufts, was joined by researchers from Medidata in New York that funded the project, contract research organizations, and pharmaceutical companies to assess the impact of unplanned changes in clinical trials, and better understand their causes. This new inquiry updated a similar study done in 2010.
Getz and colleagues reviewed records from 836 clinical trials from early stage studies to late-stage and post-approval follow-up inquiries with protocols, or plans, approved between 2010 and 2013. The team identified and tallied the trials with changes in protocols, then sampled 136 of these protocol amendments to gauge their overall impact. The researchers then drilled down further into 52 protocol amendments to calculate direct costs for implementing the changes, which they outlined in the journal article and companion Tufts report.
The team found more than half (57%) of the clinical trials had to make 1 or more major changes in protocols once the studies were underway. Moreover, nearly half (45%) of the changes were considered avoidable, an increase from 2010 when about 1 in 3 (33%) of the changes were deemed avoidable. Many of the changes resulted from problems encountered in recruitment or retention of participants, as well as changes in study procedure, which the authors believe could have been avoided through better trial planning or design.
In addition, a little more than 1 in 3 (35%) of changes were caused by typographical corrections. Only about 1 in 5 protocol changes were requested by regulatory authorities, of which the vast majority (86%) were considered unavoidable......
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