Tuesday, April 30, 2013
Is Early Detection of Cancer with Circulating Biomarkers Feasible?
"Early cancer detection before metastasis in
asymptomatic patients is one of the primary objectives of cancer
research initiatives.
Early detection generally means more opportunities for
intervention that ultimately lead to improvement in patient outcomes.
Many studies have concluded that early detection of
breast cancer in women older than 50 years with mammogram screening
programs
improves survival by 20%–25% (1).
Patients with stage I ovarian cancer detected by transvaginal
ultrasound (approximately 42-mm mean tumor diameter) have
a 5-year survival rate of 93%, compared with 30% for
patients with stage III to stage IV disease at diagnosis (2).
Many blood-based biomarker tests are
routinely used in clinical practice for cancer surveillance, therapy
monitoring, prognosis,
and risk stratification. Most experts, however, would
agree that there are no blood-based biomarkers suitable for population
screening or early diagnosis of cancer, despite the
considerable intellectual and financial efforts worldwide.
Editorial: Financial Disclosure, Industry Sponsorship, and Integrity in Cancer Research Reporting
.....In short, there is much
left to do to ensure integrity in cancer research reporting. Regrettably,
disclosure alone has not proved sufficient,32 and until such time as
additional safeguards are in place, a credibility gap will likely persist.By
the same token, it is overly cynical to judge a study as tainted simply
because it is funded by industry. As always, evaluating the quality and
integrity of a clinical trial requires careful assessment of the trial’s
design and conduct, using scientific rigor to interpret the results,
accompanied by a healthy dose of common sense.10,33"
Authors' Response: Correspondence: Estimating Cancer Risks From a Retrospective Cohort of Patients With MMR Gene Mutations
Reply to V. Bonadona et al
We wish to reply to the valuable comments of Bonadona et al1
concerning our study 2 on the risks of less-common cancers in patients
with proven gene mutations and Lynch syndrome......
......We agree with Bonadona and her colleagues that such analyses should make use of appropriate methods to minimize biases as much as possible and to reliably assess the role of different risk factors. To our knowledge, such international collaborations are currently being planned.
Correspondence: Estimating Cancer Risks From a Retrospective Cohort of Patients With MMR Gene Mutations
Correspondence
TO THEEDITOR:
Engel et al1 recently provided age-specificcumulative
risks of less common cancers (ie, noncolorectal and nonendometrial)
in Lynch syndrome. Using the Kaplan-Meier method, risks
were estimated by age, sex, and mutated genes in a large German and
Dutch cohort of 2,118 patients who were proven carriers of MLH1,
MSH2, and MSH6 mutations. The authors stated that ascertainment
bias should not have severely affected their estimates because most families were identified by clustering or early onset of colorectal or endometrial cancer. However, selection of patients from the German and Dutch national Lynch syndrome registries was based on Amsterdam criteria and Bethesda guidelines, which include tumors from the whole Lynch syndrom spectrum. We are therefore concerned that a potential bias in cancer-risk estimates may have been introduced by the fact that certain rarer tumors contributed to the recruitment of families......
Risk of osteonecrosis of the jaw in cancer patients receiving Denosumab: a meta-analysis of seven randomized controlled trials
Abstract
Conclusions
The use of denosumab
is associated with an increased risk of developing ONJ when compared
with BP treatment or placebo, although the increased risk was not
statistically significant between denosumab and BP treatment. Further
studies are still needed to establish guidelines for the prevention and
effective treatment of ONJ.
EU Science Funding Groups Lay Out Open Access Guidelines | GenomeWeb Daily News | GenomeWeb
Blogger's Note: to view- register/free
GenomeWeb
NEW YORK (GenomeWeb News) – European science funding organizations are planning to enact open access policies requiring publications resulting from studies they funded to be made publicly available as soon as possible. Toward that end, the groups have now agreed to a set of common principles to guide the transition away from the current publication model.....
A Study to Evaluate the Cause of Bone Demineralization in Gynecological Cancer Survivors
subscription required ($$)
Conclusions. Women treated for gynecological malignancies with surgery and adjuvant chemotherapy have significantly lower BMDs than age-matched women who have undergone oophorectomy for noncancer indications. Prospective evaluation of BMD in gynecological cancer patients is recommended to facilitate interventions that will reduce the risk of subsequent fragility fractures.
CoDP: predicting the impact of unclassified genetic variants in MSH6 by the combination of different properties of the protein (Lynch Syndrome)
Blogger's Note: of interest (technical) for Lynch Syndrome patients/dual primaries - ovarian/uterine and those with unclassifed variants/unknown significance; included are references regarding MSH6 etc
open access
Conclusion
In this paper, we provide a human curated data set for MSH6 missense variants, and
CoDP, the prediction tool, which achieved better accuracy for predicting the impact
of missense variants in MSH6 than any other known tools. CoDP is available at http://cib.cf.ocha.ac.jp/CoDP/.
The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.
Screening for BRCA1 and BRCA2 Mutations among French-Canadian Breast Cancer Cases Attending an Outpatient Clinic in Montreal
Abstract
OBJECTIVE:
To estimate the prevalence of BRCA mutations among early-onset and familial French-Canadian breast cancer patients in a single institution.METHODS:
Study subjects were French-Canadian women with DCIS or invasive breast cancer (incident or prevalent) who were treated and followed at a single breast cancer clinic affiliated with the Research Center of University of Montreal (CRCHUM), who were either aged less than 50 years at diagnosis or who were 50 years or older and with at least two affected first- or second-degree relatives. Subjects were tested for six founder mutations (three in BRCA1 and three in BRCA2).DICER1 Syndrome: A New Cancer Syndrome
DICER1 Syndrome
"Recently, germline mutations of DICER1 have been identified in patients with rare neoplasms suggesting the existence of a newly discovered cancer prone syndrome. Initially, DICER1 mutations were identified in patients with familial pleuropulmonary blastoma. Subsequently, additional manifestations of the syndrome have been identified including cystic nephroma, medulloepithelioma, Sertoli-Leydig cell tumor (Blogger's Note: subtype - ovarian cancer) and others. The DICER1 gene encodes an enzyme that is involved in the biogenesis of microRNAs. The entire tumor spectrum and the respective tumor risks are unknown. We are in the process of launching a natural history study aimed at identifying more information on this new cancer syndrome."
Apr 29, 2013: Cancer Risks for BRCA1 and BRCA2 Mutation Carriers: Results From Prospective Analysis of EMBRACE
EMBRACE
- Received July 24, 2012.
- Revision received March 20, 2013.
- Accepted March 22, 2013.
Background Reliable estimates of cancer risk are critical for guiding management of BRCA1 and BRCA2
mutation carriers. The aims of this study were to derive penetrance
estimates for breast cancer, ovarian cancer, and contralateral
breast cancer in a prospective series of
mutation carriers and to assess how these risks are modified by common
breast cancer
susceptibility alleles.
Methods Prospective cancer risks were estimated using a cohort of 978 BRCA1 and 909 BRCA2
carriers from the United Kingdom. Nine hundred eighty-eight women had
no breast or ovarian cancer diagnosis at baseline,
1509 women were unaffected by ovarian cancer,
and 651 had been diagnosed with unilateral breast cancer. Cumulative
risks were
obtained using Kaplan–Meier estimates.
Associations between cancer risk and covariables of interest were
evaluated using Cox
regression. All statistical tests were
two-sided.
Results The average cumulative risks by age 70 years for BRCA1 carriers were estimated to be 60% (95% confidence interval [CI] = 44% to 75%) for breast cancer, 59% (95% CI = 43% to 76%)
for ovarian cancer, and 83% (95% CI = 69% to 94%) for contralateral breast cancer. For BRCA2 carriers, the corresponding risks were 55% (95% CI = 41% to 70%) for breast cancer, 16.5% (95% CI = 7.5% to 34%) for ovarian
cancer, and 62% (95% CI = 44% to 79.5%) for contralateral breast cancer. BRCA2
carriers in the highest tertile of risk, defined by the joint genotype
distribution of seven single nucleotide polymorphisms
associated with breast cancer risk, were at
statistically significantly higher risk of developing breast cancer than
those
in the lowest tertile (hazard ratio = 4.1, 95%
CI = 1.2 to 14.5; P = .02).
Conclusions Prospective risk estimates confirm that BRCA1 and BRCA2
carriers are at high risk of developing breast, ovarian, and
contralateral breast cancer. Our results confirm findings from
retrospective studies that common breast cancer
susceptibility alleles in combination are predictive of breast cancer
risk
for BRCA2 carriers.
GenomeWeb: To Find a New Treatment (mutations/variants - research)
Blogger's Note: a test of the My Cancer Genome site - ovarian/colorectal did not show in the drop down box 'Msh2)
To Find a New Treatment
"With more and more cancers being parsed by their genetic mutations, even oncologists can have a hard time keeping up with the variants and which treatments go with them, the New York Times writes.
"There are so many genes and so many mutations," William Pao from Vanderbilt University tells the Times. "The human brain can't memorize all those permutations." He and some colleagues developed a website called My Cancer Genome to keep all those mutations and drugs straight for doctors and patients. For example, clinicians can search the database, which is maintained by a team of more than 50 people from 20 different institutions, for different cancers and mutations and then for related treatments or drug trials.
Identification of rare genetic variants contributing to human diseases - call for abstract submission/s
Research Topics
Deadline for abstract submission:
01 Jul 2013
Deadline for full article submission:
01 Nov 2013
1.Rare variants genotyping/calling, QC, validation and control for genotyping/sequencing error;
2.Discovering novel variants (including recent mutations, de novo mutations, etc);
3.Annotation and prediction of functions of rare variants;
4.Discovering rare, causal variants in mendelian diseases (experimental design, statistical methods, power, sample size, etc);
5.Associating rare variants with human complex diseases (experimental design, statistical methods, power, sample size, etc);
6.Burden and non-burden test methods for genes, pathways and other self-defined variant sets;
7. Estimating effect size and heritability of rare variants.
8.Integrative analysis of rare and common variants;
9.Any disease-specific applications relevant to this topic
blog: The head of the House Committee on Science does not understand how science works | The Curious Wavefunction, Scientific American Blog Network
Scientific American Blog Network
"It’s been said many times. Curiosity-driven research with no immediate application or goal is what has primarily led to science’s greatest discoveries as well as our high standard of living. It is what has led to the ascendancy of American science during the twentieth century. If you want great discoveries to happen, the recipe is clear; get the best scientists together and leave them alone.
And yet politicians just don’t get it........
Patenting genes: balancing public health and private interest | Globalnews.ca
Blogger's Note: this all relates to the U.S. supreme court case/Myriad patent (BRCA patent) issues; note that Myriad also holds patients such as Colaris (colorectal/Lynch Syndrome)
~~~~~~~~~~
Patenting genes
Posted by Genome Alberta via globalnews.ca
“We’re kind of in the worst of all worlds,” Gold said. “It’s not just the Myriad patents, but it’s a whole bunch of other companies that are coming in as well. They all have similarly constructed patent claims and it’s those that will cause worry.”
paywalled: Risk of transferring malignant cells with transplanted frozen-thawed ovarian tissue
Fertility and Sterility
Volume 99, Issue 6, May 2013, Pages 1514–1522
"Ovarian
tissue cryopreservation and transplantation is a real option to
preserve and restore fertility in young cancer patients. However, there
is a concern regarding the possible presence of malignant cells in the
ovarian tissue, which could lead to recurrence of the primary disease
after reimplantation. A review of the existing literature was done to
evaluate the risk of transplanting malignant cells in case of the main
malignant indications for ovarian tissue cryopreservation. For ovarian
tissue from patients with hematologic malignancies, it is of paramount
importance to identify minimal residual disease before ovarian tissue
transplantation. Indeed, these pathologies, reviewed here in detail, are
considered to be most at risk of ovarian metastasis."
- Figure 1. Histologic analysis of an ovarian fragment recovered from a mouse after 6 months' grafting (acute lymphoblastic leukemia patients). A human follicle is encircled by a large number of lymphocytes. Normal ovarian stroma is no longer present.
- Figure 2. Ovarian fragments from a non-Hodgkin lymphoma (NHL) patient. (A) Immunohistochemistry anti-CD20 (against NHL cells) is negative in the cortex (blue staining) and positive in the medulla (brown staining). Magnification of the white rectangle is represented in (B) and magnification of the black rectangle in (C). (B) Cells with an enlarged nucleus and patchy chromatin are disseminated in the tissue and stain strongly for anti-CD20. (C) Piece of cancer cell-free cortex. Follicles present in the cortex appear healthy. (D) Another fragment from the same patient shows massive invasion by NHL cells in the cortex.
- Table 1. Patients and pathology characteristics with PCR markers tested on frozen-thawed ovarian tissue.
- Note: Table showing the number of chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) patients, their age at the time of ovarian tissue cryopreservation (OTC), and the type of gonadotoxic chemotherapy received before OTC (CML patients received hydroxycarbamide with or without imatinib). Molecular markers present in blood or bone marrow at the time of diagnosis were tested by polymerase chain reaction (PCR) on frozen-thawed ovarian tissue. Adapted from Dolmans et al. (9). Ig = immunoglobulin; NA = not applicable; TCR = T-cell receptor.
- View Within Article
- Table 2. Experimental studies on the risk of transmitting malignant cells in case of lymphoma.
- Note: Experiments are divided into two groups, depending on whether ovarian tissue from Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) patients was used. All studies used histology, and some were completed by the addition of either immunohistochemistry or xenografting experiments. One study reported autografting results.
- View Within Article
- Table 3. Risk of ovarian metastasis according to cancer type.
- View Within Article
Pet Cancer Treatments Improving - media/video
Pet Cancer Treatments Improving
"An estimated 1-in-3 dogs and 1-in-4 cats will get cancer at some point in their lives, but new treatments are helping pets live longer and better lives with fewer side effects....
paywalled: Characteristics of Oncology Clinical TrialsInsights From a Systematic Analysis of ClinicalTrials.gov
JAMA Network
Published online
April 29, 2013
Importance
Clinical trials are essential to cancer care, and data
about the current state of research in oncology are needed to develop
benchmarks and set the stage for improvement.
Objective To perform a comprehensive analysis of the national oncology clinical research portfolio.
Design All interventional clinical studies registered on ClinicalTrials.gov between October 2007 and September 2010 were identified using Medical Subject Heading terms and submitted conditions. They were reviewed to validate classification, subcategorized by cancer type, and stratified by design characteristics to facilitate comparison across cancer types and with other specialties.
Results Of 40 970 interventional studies registered between October 2007 and September 2010, a total of 8942 (21.8%) focused on oncology. Compared with other specialties, oncology trials were more likely to be single arm (62.3% vs 23.8%; P < .001), open label (87.8% vs 47.3%; P < .001), and nonrandomized (63.9% vs 22.7%; P < .001). There was moderate but significant correlation between number of trials conducted by cancer type and associated incidence and mortality (Spearman rank correlation coefficient, 0.56 [P = .04] and 0.77 [P = .001], respectively). More than one-third of all oncology trials were conducted solely outside North America.
Conclusions and Relevance There are significant variations between clinical trials in oncology and other diseases, as well as among trials within oncology. The differences must be better understood to improve both the impact of cancer research on clinical practice and the use of constrained resources.
Objective To perform a comprehensive analysis of the national oncology clinical research portfolio.
Design All interventional clinical studies registered on ClinicalTrials.gov between October 2007 and September 2010 were identified using Medical Subject Heading terms and submitted conditions. They were reviewed to validate classification, subcategorized by cancer type, and stratified by design characteristics to facilitate comparison across cancer types and with other specialties.
Results Of 40 970 interventional studies registered between October 2007 and September 2010, a total of 8942 (21.8%) focused on oncology. Compared with other specialties, oncology trials were more likely to be single arm (62.3% vs 23.8%; P < .001), open label (87.8% vs 47.3%; P < .001), and nonrandomized (63.9% vs 22.7%; P < .001). There was moderate but significant correlation between number of trials conducted by cancer type and associated incidence and mortality (Spearman rank correlation coefficient, 0.56 [P = .04] and 0.77 [P = .001], respectively). More than one-third of all oncology trials were conducted solely outside North America.
Conclusions and Relevance There are significant variations between clinical trials in oncology and other diseases, as well as among trials within oncology. The differences must be better understood to improve both the impact of cancer research on clinical practice and the use of constrained resources.
Cancer studies often lack necessary rigor to answer key questions
studies
Story Source:
The above story is reprinted from materials provided by Duke University Medical Center.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Implementation of tumor testing for lynch syndrome in endometrial cancers at a large academic medical center (of interest to those with dual primaries ovarian/endometrial)
Abstract
Highlights
- •
- There were no differences in age, histology, grade, stage, or BMI in patients with Lynch syndrome versus sporadic tumors.
- •
- Universal screening in endometrial cancers is practical and eliminates the chance for missing eligible cases.
- •
- Lynch syndrome screening in endometrial cancer is successfully implemented with collaboration among genetic counselors, gynecologic oncologists, and pathologists.
Results
Two
hundred and forty-five endometrial cancers (average age, 57 years) were
screened. Sixty-two patients (25%) had abnormal results, and 42
patients were referred for genetic counseling. Of the 42 patients, 34
underwent genetic counseling, 28 pursued genetic testing, and 11 were
diagnosed with LS. When age and pathology criteria were used, 27
eligible cases were overlooked for screening and 3 cases of LS were
found only because a clinician requested screening.
~~~~~~~~~~~~~~~
Objectives
Lynch
syndrome (LS) is a hereditary condition that increases the risk for
endometrial and other cancers.
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