Wednesday, January 07, 2015
Tuesday, January 06, 2015
Next-Generation Sequencing of the BRCA1 and BRCA2 Genes for the Genetic Diagnostics of Hereditary Breast and/or Ovarian Cancer
abstract
Genetic testing for hereditary breast and/or ovarian cancer mostly relies on laborious molecular tools that use Sanger sequencing to scan for mutations in the BRCA1 and BRCA2 genes. We explored a more efficient genetic screening strategy based on next-generation sequencing of the BRCA1 and BRCA2 genes in 210 hereditary breast and/or ovarian cancer patients. We first validated this approach in a cohort of 115 samples with previously known BRCA1 and BRCA2 mutations and polymorphisms. Genomic DNA was amplified using the Ion AmpliSeq BRCA1 and BRCA2 panel. The DNA Libraries were pooled, barcoded, and sequenced using an Ion Torrent personal genome machine sequencer. The combination of different robust bioinformatics tools allowed detection of all previously known pathogenic mutations and polymorphisms in the 115 samples, without detecting spurious pathogenic calls. We then used the same assay in a discovery cohort of 95 uncharacterized hereditary breast and/or ovarian cancer patients for BRCA1 and BRCA2. In addition, we describe the allelic frequencies across 210 hereditary breast and/or ovarian cancer patients of 74 unique definitely and likely pathogenic and uncertain BRCA1 and BRCA2 variants, some of which have not been previously annotated in the public databases. Targeted next-generation sequencing is ready to substitute classic molecular methods to perform genetic testing on the BRCA1 and BRCA2 genes and provides a greater opportunity for more comprehensive testing of at-risk patients.
7th Asian Oncology Summit and 11th Annual Conference of the Organisation for Oncology and Translational Research
conference notice
Last chance to submit abstracts: January 9, 2015
Please remember to submit abstracts for the 2015 Asian Oncology Summit (AOS) ‘Cause and effect: aetiology and medicine working together to improve health’ by Friday, January 9, 2015.
Abstracts are invited for short oral contributions and poster presentations alongside the invited lectures on the following topics.
- Prevention
- Palliative care
- Gastrointestinal cancer
- Breast cancer
- Genitourinary cancer
- Lung cancer
- Translational oncology
- Haematological oncology
- Supportive oncology
- Melanoma
- Sarcoma
- Head and neck cancer
- Health economics
- Radiation oncology
- Gynaecological cancer
- Pharmacoeconomics
- Health-care delivery
- Molecular pathology
- Endocrine late effects of cancer
End of cancer-genome project prompts rethink
Scientific American
"... On December 2, Staudt announced that once TCGA is completed, the NCI will continue to intensively sequence tumours in three cancers: ovarian, colorectal and lung adenocarcinoma. It then plans to evaluate the fruits of this extra effort before deciding whether to add back more cancers....
Don’t blame the flu for ER congestion
The Globe and Mail
".... We are told, in public service announcements from health regions, in press releases from hospitals and in newspaper headlines, that the flu is to blame.
That’s B.S.
Our emergency rooms are overflowing because of bad planning and misplaced priorities........
Friday, January 02, 2015
TIME: Most Cancer Is Beyond Your Control
Note: it is very unfortunate that the original research paper is NOT open access; includes comments on ovarian and other cancers eg. colon, brain etc...
TIME
Commentary: The bad luck of cancer
The bad luck of cancer (requires subscription for full access)
Biomedicine
The bad luck of cancer
"Bert Vogelstein and Cristian Tomasetti of Johns Hopkins University have put forth a mathematical analysis of the genesis of cancer that suggests many cases are not preventable.Hopkins Medicine: Bad Luck of Random Mutations Plays Predominant Role in Cancer, Study Shows - 01/01/2015
Hopkinsmedicine
Release Date: January 1, 2015
Scientists from the Johns Hopkins Kimmel Cancer Center have created a
statistical model that measures the proportion of cancer incidence,
across many tissue types, caused mainly by random mutations that occur
when stem cells divide. By their measure, two-thirds of adult cancer
incidence across tissues can be explained primarily by “bad luck,” when
these random mutations occur in genes that can drive cancer growth,
while the remaining third are due to environmental factors and inherited
genes.
“All cancers are caused by a combination of bad luck, the environment
and heredity, and we’ve created a model that may help quantify how much
of these three factors contribute to cancer development,” says Bert
Vogelstein, M.D., the Clayton Professor of Oncology at the Johns Hopkins
University School of Medicine, co-director of the Ludwig Center at
Johns Hopkins and an investigator at the Howard Hughes Medical
Institute.
“Cancer-free longevity in people exposed to cancer-causing agents, such
as tobacco, is often attributed to their ‘good genes,’ but the truth is
that most of them simply had good luck,” adds Vogelstein, who cautions
that poor lifestyles can add to the bad luck factor in the development
of cancer.
The implications of their model range from altering public perception
about cancer risk factors to the funding of cancer research, they say.
“If two-thirds of cancer incidence across tissues is explained by random
DNA mutations that occur when stem cells divide, then changing our
lifestyle and habits will be a huge help in preventing certain cancers,
but this may not be as effective for a variety of others,” says
biomathematician Cristian Tomasetti, Ph.D., an assistant professor of
oncology at the Johns Hopkins University School of Medicine and
Bloomberg School of Public Health. “We should focus more resources on
finding ways to detect such cancers at early, curable stages,” he adds.
In a report on the statistical findings, published Jan. 2 in Science,
Tomasetti and Vogelstein say they came to their conclusions by
searching the scientific literature for information on the cumulative
total number of divisions of stem cells among 31 tissue types during an
average individual’s lifetime. Stem cells “self-renew,” thus
repopulating cells that die off in a specific organ.
It was well-known, Vogelstein notes, that cancer arises when
tissue-specific stem cells make random mistakes, or mutations, when one
chemical letter in DNA is incorrectly swapped for another during the
replication process in cell division. The more these mutations
accumulate, the higher the risk that cells will grow unchecked, a
hallmark of cancer. The actual contribution of these random mistakes to
cancer incidence, in comparison to the contribution of hereditary or
environmental factors, was not previously known, says Vogelstein.
To sort out the role of such random mutations in cancer risk, the Johns
Hopkins scientists charted the number of stem cell divisions in 31
tissues and compared these rates with the lifetime risks of cancer in
the same tissues among Americans. From this so-called data scatterplot,
Tomasetti and Vogelstein determined the correlation between the total
number of stem cell divisions and cancer risk to be 0.804.
Mathematically, the closer this value is to one, the more stem cell
divisions and cancer risk are correlated.
“Our study shows, in general, that a change in the number of stem cell
divisions in a tissue type is highly correlated with a change in the
incidence of cancer in that same tissue,” says Vogelstein. One example,
he says, is in colon tissue, which undergoes four times more stem cell
divisions than small intestine tissue in humans. Likewise, colon cancer
is much more prevalent than small intestinal cancer.
“You could argue that the colon is exposed to more environmental
factors than the small intestine, which increases the potential rate of
acquired mutations,” says Tomasetti. However, the scientists saw the
opposite finding in mouse colons, which had a lower number of stem cell
divisions than in their small intestines, and, in mice, cancer incidence
is lower in the colon than in the small intestine. They say this
supports the key role of the total number of stem cell divisions in the
development of cancer.
Using statistical theory, the pair calculated how much of the variation
in cancer risk can be explained by the number of stem cell divisions,
which is 0.804 squared, or, in percentage form, approximately 65
percent.
Finally, the research duo classified the types of cancers they studied
into two groups. They statistically calculated which cancer types had an
incidence predicted by the number of stem cell divisions and which had
higher incidence. They found that 22 cancer types could be largely
explained by the “bad luck” factor of random DNA mutations during cell
division. The other nine cancer types had incidences higher than
predicted by "bad luck" and were presumably due to a combination of bad
luck plus environmental or inherited factors.
“We found that the types of cancer that had higher risk than predicted
by the number of stem cell divisions were precisely the ones you’d
expect, including lung cancer, which is linked to smoking; skin cancer,
linked to sun exposure; and forms of cancers associated with hereditary
syndromes,” says Vogelstein.
“This study shows that you can add to your risk of getting cancers by
smoking or other poor lifestyle factors. However, many forms of cancer
are due largely to the bad luck of acquiring a mutation in a cancer
driver gene regardless of lifestyle and heredity factors. The best way
to eradicate these cancers will be through early detection, when they
are still curable by surgery,” adds Vogelstein.
The scientists note that some cancers, such as breast and prostate
cancer, were not included in the report because of their inability to
find reliable stem cell division rates in the scientific literature.
They hope that other scientists will help refine their statistical model
by finding more precise stem cell division rates.
The research was funded by the Virginia and D. K. Ludwig Fund for
Cancer Research, the Lustgarten Foundation for Pancreatic Cancer
Research, the Sol Goldman Pancreatic Cancer Research Center, and the
National Institutes of Health’s National Cancer Institute (grants
P30-CA006973, R37-CA43460, RO1-CA57345 and P50-CA62924).
###
Thursday, January 01, 2015
revised: The simple math that explains why you may (or may not) get cancer
Abstract
Abstract
Some tissue types give rise to human cancers millions of times more often than other tissue types. Although this has been recognized for more than a century, it has never been explained. Here, we show that the lifetime risk of cancers of many different types is strongly correlated (0.81) with the total number of divisions of the normal self-renewing cells maintaining that tissue’s homeostasis. These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to “bad luck,” that is, random mutations arising during DNA replication in normal, noncancerous stem cells. This is important not only for understanding the disease but also for designing strategies to limit the mortality it causes.
Editor's Summary
Crunching the numbers to explain cancer
Why do some tissues give rise to cancer
in humans a million times more frequently than others? Tomasetti and
Vogelstein conclude
that these differences can be explained by the
number of stem cell divisions. By plotting the lifetime incidence of
various
cancers against the estimated number of normal
stem cell divisions in the corresponding tissues over a lifetime, they
found
a strong correlation extending over five orders
of magnitude. This suggests that random errors occurring during DNA
replication
in normal stem cells are a major contributing
factor in cancer development. Remarkably, this “bad luck” component
explains
a far greater number of cancers than do
hereditary and environmental factors.
Science/AAAS | News
"...For Vogelstein, one major message is that cancer often cannot be prevented, and more resources should be funneled into catching it in its infancy. “These cancers are going to keep on coming,” he says.
Douglas Lowy, a deputy director of the National Cancer Institute in Bethesda, Maryland, agrees, but also stresses that a great deal of “cancer is preventable” and efforts to avert the disease must continue.
Although the randomness of cancer might be frightening, those in the field see a positive side, too. The new framework stresses that “the average cancer patient … is just unlucky,” Clevers says. “It helps cancer patients to know” that the disease is not their fault."
Wednesday, December 24, 2014
Professional risk factors associated with the cancer of the ovary.Literature review. (asbestos)
abstract
The aim of this work was to review the available literature on occupational risk factors associated with ovarian cancer. A PubMed search was performed using an algorithm with the following search terms: ovary, ovarian, exposure, work, occupation. Relevant articles were selected through assessment of titles and abstracts as well as through the reference lists of related articles. A total of 54 studies were selected for this review, including 17 studies on asbestos exposure and risk of ovarian cancer and, 16 studies on other occupational factors (5 cohort studies and 11 case control studies). An increased risk of ovarian cancer has been reported for several occupations (teachers, administration employees, nurses, religious workers) and various industrial sectors (biomedical research, telephony industry, hairdresser and beautician, printing factories) with inconsistent results. Moreover, in many of these studies, individual risk factors of ovarian cancers were not considered. Despite methodological limitations of published studies, a significantly increased risk for ovarian cancer associated with asbestos exposure have been consistently reported.
A systematic review of the incidence and prevalence of cancer in multiple sclerosis
Abstract
BACKGROUND:
Studies of cancer incidence and prevalence in multiple sclerosis (MS) have produced conflicting results.OBJECTIVE:
To estimate the incidence and prevalence of cancer in persons with MS and review the quality of included studies.RESULTS:
We identified 38 studies. Estimates for incidence and prevalence varied substantially for most cancers. In population-based studies, cervical, breast, and digestive cancers had the highest incidence. The risk of meningiomas and urinary system cancers appeared higher than expected, while the risks of pancreatic, ovarian, prostate and testicular cancer were lower than expected.Conclusion: The complexity of understanding cancer risk in MS is augmented by inconsistencies in study design, and the relative paucity of age, sex and ethnicity-specific risk estimates from which the strong impact of age on the incidence of cancers can be assessed.
Genetic counseling content: How does it impact health behavior? - PubMed - NCBI
Note: abstract provides no reference to Lynch Syndrome
abstract
Women with hereditary breast-ovarian cancer face decisions about screening (transvaginal ultrasound, CA125, mammography, breast exams) and proactive (before cancer) or reactive (after cancer) surgery (oophorectomy, mastectomy). The content of genetic counseling and its relation to these key health behaviors is largely unexamined. Ashkenazi Jewish women (n = 78) were surveyed through the process of genetic testing and had audiorecorded counseling sessions available for Linguistic Inquiry and Word Count analysis. Proportions for participant and counselor cognitive and affective content during sessions were used as primary predictor variables in linear mixed models for change in intentions for screening and treatment and in self-reported screening. Cognitive and affective content were important predictors of behavior. Counselor cognitive content was associated with ovarian screening. An interaction effect also emerged for CA-125, such that counselor cognitive content plus participant cognitive content or counselor affective content were associated with more screening. Teasing out the factors in risk communication that impact decision-making are critical, and affect from a risk communicator can spur action, such as cancer screening.
Systematic evaluation of bevacizumab in recurrent ovarian cancer treatment
abstract
Purpose:
This study aimed to evaluate the efficacy and safety of bevacizumab in
the treatment of recurrent ovarian cancer.
Methods: The Cochrane Library, MEDLINE, and EMBASE were searched. Data regarding the use of bevacizumab in recurrent ovarian cancer were collected from randomized controlled trials (RCTs). Data were evaluated with the Cochrane systematic method, and statistical analysis was performed with the RevMan 5.2 software. Two RCTs comprising a total of 845 patients were included.
Results: Bevacizumab combined with conventional chemotherapy prolonged the progression-free survival (PFS) (hazard ratio [HR] 0.48; 95% confidence interval [CI], 0.41-0.56), without significantly altering the overall survival (OS) (HR 1.03; 95% CI 0.79-1.33). Adverse events (NCI-CTCAE v.4.0) associated with bevacizumab were ≥ grade 3 hypertension (relative risk [RR] 2.30; 95% CI 1.39-3.83) and bleeding (RR 4.76; 95% CI 1.38-16.37).
Conclusions: Bevacizumab prolonged the PFS of patients with recurrent ovarian cancer. Additional high-quality randomized controlled trials are needed to verify these results.
Methods: The Cochrane Library, MEDLINE, and EMBASE were searched. Data regarding the use of bevacizumab in recurrent ovarian cancer were collected from randomized controlled trials (RCTs). Data were evaluated with the Cochrane systematic method, and statistical analysis was performed with the RevMan 5.2 software. Two RCTs comprising a total of 845 patients were included.
Results: Bevacizumab combined with conventional chemotherapy prolonged the progression-free survival (PFS) (hazard ratio [HR] 0.48; 95% confidence interval [CI], 0.41-0.56), without significantly altering the overall survival (OS) (HR 1.03; 95% CI 0.79-1.33). Adverse events (NCI-CTCAE v.4.0) associated with bevacizumab were ≥ grade 3 hypertension (relative risk [RR] 2.30; 95% CI 1.39-3.83) and bleeding (RR 4.76; 95% CI 1.38-16.37).
Conclusions: Bevacizumab prolonged the PFS of patients with recurrent ovarian cancer. Additional high-quality randomized controlled trials are needed to verify these results.
Low-dose aspirin use and the risk of ovarian cancer in Denmark
abstract
Background A
comprehensive body of evidence has shown that aspirin has
cancer-preventive effects, particularly against gastrointestinal
cancer, but its effects on the risk of ovarian
cancer are less well established. This nationwide case-control study
examined
the association between low-dose aspirin and the
risk of ovarian cancer.
Patients and methods
We identified all patients in the Danish Cancer Registry aged 30–84
years old with a histologically verified first diagnosis
of epithelial ovarian cancer during 2000–2011.
Each patient was sex- and age-matched to 15 population controls using
risk-set
sampling. Prescription use, comorbidity,
reproductive history and demographic characteristics data were obtained
from nationwide
registries. Use of low-dose (75–150 mg) aspirin
was defined according to dose and duration and consistency of use.
Conditional
logistic regression was used to calculate odds
ratios (ORs) with 95% confidence intervals (CIs) for the association
between
low-dose aspirin use and the risk of epithelial
ovarian cancer, both overall and for specific histological types.
Results For 4,103
ovarian cancer cases and 58,706 population controls, the adjusted OR for
epithelial ovarian cancer associated with
ever use (≥2 prescriptions) of low-dose aspirin
was 0.94 (95% CI: 0.85–1.05). ORs for epithelial ovarian cancer were
lower
with the use of 150 mg aspirin tablets (OR=0.82;
95% CI: 0.68–0.99) and with long-term use (≥5 years) of low-dose
aspirin
(OR=0.77; 95% CI: 0.55–1.08). Continuous
long-term use of low-dose aspirin, defined as close consecutive
prescriptions, was
associated with a further reduction in OR (0.56;
95% CI: 0.32–0.97). For histological types of epithelial ovarian
cancer,
the strongest inverse associations with low-dose
aspirin use were seen for mucinous and endometrioid tumours.
Conclusion This nationwide case-control study indicates that low-dose aspirin use may be associated with reduced risk of epithelial
ovarian cancer.
Short-Term Risk of Colorectal Cancer in Individuals With Lynch Syndrome: A Meta-Analysis
abstract
Purpose For carriers
of germline mutations in DNA mismatch repair genes, the most relevant
statistic for cancer prevention is colorectal
cancer (Lynch syndrome) risk, particularly in
the short term.
Tuesday, December 23, 2014
Primary peritoneal carcinoma after prophylactic oophorectomy in women with a family history of ovarian cancer - Cancer Genetics and Epigenetics
open access
Background According
to previous reports, primary peritoneal carcinoma indistinguishable
from primary ovarian adenocarcinoma had developed in five women with a
history of familial ovarian cancer who had undergone prophylactic
oophorectomy.
Methods The records
from the Gilda Radner Familial Ovarian Cancer Registry were reviewed for
instances of prophylactic oophorectomy and cases of primary peritoneal
carcinoma occurring after prophylactic oophorectomy.
Results From 2011
through July 2012, the Gilda Radner Familial Ovarian Cancer Registry
accessioned 931 families (a total of 2221 cases of familial ovarian
cancer). Currently, 324 women in these families have undergone
prophylactic oophorectomy as a preventive measure against the subsequent
development of ovarian cancer. Primary peritoneal carcinoma
indistinguishable histologically from primary ovarian adenocarcinoma has
developed in six of these women 1-27 years after prophylactic
oophorectomy.
Conclusions Based on
this finding and other reports of such primary peritoneal carcinoma, a
prospective international study is planned. This study will compare the
incidence of peritoneal carcinoma in first- or second-degree relatives
who underwent prophylactic oophorectomy because of a family history of
ovarian cancer with that of those who did not undergo prophylactic
oophorectomy.
The complete article is available as a Provisional PDF if requested. The fully formatted PDF and HTML versions are in production.
Neurotoxicity in Ovarian Cancer Patients on GOG 218
abstract
Neurotoxicity in Ovarian Cancer Patients on Gynecologic Oncology Group (GOG) Protocol 218: Characteristics Associated with Toxicity and the Effect of Substitution with Docetaxel: An NRG Oncology/Gynecologic Oncology Group study.
OBJECTIVES:
To describe characteristics associated with neurotoxicity (NT) in advanced ovarian cancer patients treated on Gynecologic Oncology Group 218 and examine effect of substituting docetaxel for paclitaxel in these patients.METHODS:
The development of NT was defined as Common Toxicity Criteria grade (G) ≥1. The association between substitution with docetaxel and NT improvement was explored with generalized estimating equations adjusting for treatment cycle and NT grading at previous cycle.RESULTS:
Of 1,864 evaluable patients, 1,329 (71%) developed G≥1 NT during the study. Nearly half appeared within the first two cycles of chemotherapy, with 31% experiencing G≥2. Older patients or those with worse quality of life (QoL) scores at baseline (p<0.05) were more likely to experience NT. One-hundred-six patients received docetaxel as substitute for paclitaxel. Of them, 47 patients started with docetaxel at cycle one due to reaction to paclitaxel (n=32), fear of NT (n=4), other reasons (n=11), whereas 59 patients switched to docetaxel during cycle 2-6 due to NT (n=32), reaction to paclitaxel (n=19), and other reasons (n=8). Although the protocol instructed otherwise, the majority continued paclitaxel despite G≥2 NT symptoms. There was no evidence that substitution with docetaxel improved NT (Odds Ratio): 1.57; 95% CI 0.98-2.54; p>0.05). Of 59 patients who switched to docetaxel, only seven (12%) discontinued taxane prior to chemotherapy completion. A roughly equal chance of worsening NT was reported on paclitaxel (6%) as on docetaxel (5%).CONCLUSIONS:
Age and worse QoL at baseline are associated with NT. Substitution of docetaxel did not improve NT symptoms.Racial disparity in 30-day morbidity and mortality after surgery for ovarian cancer
abstract
CONCLUSIONS:
African American race was not an independent predictor of poor 30-day outcomes. Interestingly, AAs with OC are underrepresented in quality-seeking hospitals. Efforts to minimize this racial disparity should target optimization of comorbidities and improving access to high-volume centers for AA women.Monday, December 22, 2014
European recommendations for biomarker-based chemoprevention trials
open access-ecancermedicalscience
Abstract
Chemoprevention or the now more preferred ‘cancer prevention’ is the
long-term administration of a biological or chemical agent to reduce the
risk of cancer. This approach has long been active in individuals at
high risk of developing breast or colon cancer. The aim of this expert
meeting was to review the current status of the field of cancer
prevention and potential, emerging biomarkers specifically focusing on
breast, colon, and lung cancer but also with sessions on ovary and
prostate.......
A survey of treatment approaches of malignant ascites in Germany and Austria (gasto/gyn/medonc)
Abstract
BACKGROUND:
Malignant
ascites (MA) is a common manifestation of advanced cancer. Currently,
there are no evidence-based guidelines for the management of MA. We
conducted a survey with physicians throughout Germany and Austria, to
get an overview of current approaches and opinions in the treatment of
MA.
METHODS:
One hundred and twenty-eight medical oncologists (MO), gastroenterologists (GE), and gynecologists (GYN) completed an electronic questionnaire consisting of 33 questions.CONCLUSIONS:
Repeated PC is the main pillar of treatment of MA; its effect is only temporary and requires significant hospital resources. Further treatment strategies of MA have to be evaluated in prospective studies. Targeted therapies like catumaxomab and VEGF inhibitors should be integrated into these.Sunday, December 21, 2014
Distribution and case-fatality ratios by cell-type for ovarian carcinomas: A 22-year series....
abstract
Distribution and case-fatality ratios by cell-type for ovarian carcinomas: A 22-year series of 562 patients with uniform current histological classification
Highlights
- •
- Among 562 ovarian cancers classified by cell-type, high grade serous carcinoma and its variants accounted for 85% of tumor deaths
- •
- Reproducibility of cell-type designation among gynecologic pathology experts was excellent
- •
- 1.7% of type II tumors (high grade serous carcinomas and variants) were FIGO stage I with comprehensive surgical staging
Background
Ovarian carcinoma is comprised of several different cell types
reflecting different clinicopathologic features. Pathologic criteria for
distinguishing cell types have evolved, and therefore non-contemporary
literature on ovarian cancer may have limited current relevance. A new
dualistic model of pathogenesis that distinguishes type I (endometrioid,
mucinous, clear cell and low grade serous carcinomas) from type II
(high grade serous carcinomas and carcinosarcomas) tumors has become
widely accepted.
Methods
A
cohort of 562 patients with invasive ovarian carcinoma from a large
community hospital practice was reviewed. Cell type, FIGO stage,
mortality and interpathologist diagnostic reproducibility were analyzed.
Results
Advanced
stage ovarian carcinomas were type II in 86% of cases while low stage
tumors were most often type I. Only 1.7% of type II tumors were
confirmed to be stage I with comprehensive surgical staging. Type II
tumors accounted for 85% of deaths, and clear cell carcinomas, 5% of
deaths. Cell type-specific case-fatality ratios for type II tumors were
62% and 79% for high grade serous carcinoma and carcinosarcoma,
respectively. For type I tumors, case-fatality ratios were 38%, 36%, 27%
and 13% for low grade serous, clear cell, endometrioid and mucinous
carcinomas, respectively. The kappa value for diagnostic reproducibility
among 3 gynecologic pathologists was 0.83.
Conclusions
Current
diagnostic criteria confirm that high grade serous carcinoma and
carcinosarcoma account for the vast majority (85%) of ovarian cancer
deaths. Cell type designation is highly reproducible among gynecologic
pathologists. Type II tumors are rarely stage I (< 2%) when
comprehensively staged by a gynecologic oncologist.
Prevalence of Germline Mutations in Cancer Predisposition Genes in Patients with Pancreatic Cancer
abstract
BACKGROUND:& Aims:
We investigated the prevalence of germline mutations in APC, ATM, BRCA1, BRCA2, CDKN2A, MLH1, MSH2, MSH6, PALB2, PMS2, PRSS1, STK11, and TP53 in patients with pancreatic cancer.
METHODS:
The Ontario Pancreas Cancer Study enrolls consenting participants with pancreatic cancer from a province-wide electronic pathology database; 708 probands were enrolled from April 2003 through August 2012. To improve precision of BRCA2 prevalence estimates, 290 probands were randomly selected from 3 strata, based on family history of breast and/or ovarian cancer, pancreatic cancer, or neither. Germline DNA was analyzed by next-generation sequencing using a custom multiple-gene panel. Mutation prevalence estimates were calculated from the sample for the entire cohort.RESULTS:
Eleven pathogenic mutations were identified: 3 in ATM, 1 in BRCA1, 2 in BRCA2, 1 in MLH1, 2 in MSH2, 1 in MSH6, and 1 in TP53. The prevalence of mutations in all 13 genes was 3.8% (95% confidence interval, 2.1%-5.6%). Carrier status was significantly associated with breast cancer in the proband or first-degree relative (P<.01), and colorectal cancer in the proband or first-degree relative (P<.01), but not family history of pancreatic cancer, age of diagnosis, or stage at diagnosis. Of patients with a personal or family history of breast and colorectal cancer, 10.7% (4.4%-17.0%) and 11.1% (3.0%-19.1%) carried pathogenic mutations, respectively.CONCLUSIONS:
A small but clinically important proportion of pancreatic cancer is associated with mutations in known predisposition genes. The heterogeneity of mutations identified in this study demonstrates the value of using a multiple-gene panel in pancreatic cancer.Is the endometrial evaluation routinely required in patients with adult granulosa cell tumors of the ovary?
abstract
OBJECTIVE:
granulosa cells tumors (GCTs) are the most common estrogen-secreting ovarian tumors; perhaps due to the persistent hyperestrogenism, a wide spectrum of associated endometrial pathologies ranging from endometrial hyperplasia to carcinoma has been documented in patients with GCTs. The aim of this study is to evaluate the incidence of endometrial pathologies in a large series of GCTs patients treated in MITO centers.
METHODS:
a retrospective multi-institutional review of patients with granulosa cell tumors of the ovary treated or referred to MITO centers was conducted. Descriptive statistics were used to characterize the patient population and to assess the association of GCT and endometrial abnormalities at the time of diagnosis; multivariate regression analysis was also performed to identify independent predictors of endometrial abnormalities.RESULTS:
a total of 150 patients with primary adult GCT was identified. During the preoperative assessment, endometrial pathology was found in 35.9% of symptomatic patients and in 90.9% of asymptomatic women with endometrial thickening at transvaginal ultrasound. At the time of surgery, hyperplasia was documented in 29.2% of patients, whereas endometrial cancer occurred in 7.5% of patients. Almost all of the patients (97.6%) with endometrial hyperplasia were older than 40 years. All patients with endometrial cancer were older than 40 years and postmenopausal.CONCLUSIONS:
endometrial carcinoma/atypical hyperplasia were commonly observed in GCT patients>40 years; based on these data, endometrial sampling should be performed in symptomatic women at least 40 years of age. In asymptomatic women<40 years, endometrial sampling is of low yield.Saturday, December 20, 2014
A multicenter, non-randomized, phase II study of docetaxel and carboplatin administered every 3 weeks as 2nd line chemotherapy in patients with first relapse of platinum sensitive epithelial ovarian, peritoneal or fallopian tube
open access
Conclusions
The three-weekly regimen of docetaxel in combination with carboplatin was feasible
and active as second-line treatment of platinum-sensitive ovarian, peritoneal and
Fallopian tube cancer. The major toxicity was neutropenia, while the frequency of
peripheral neuropathy was low.
Incidence of breast and gynaecological cancers by ethnic group in England, 2001-2007
open access
Conclusions
Our study provides evidence that the risk of breast and gynaecological cancers varies
by ethnic group and that those groups typically grouped together are not homogenous
with regards to their cancer risk. Furthermore, several of our findings cannot be
readily explained by known risk factors and therefore warrant further investigation.
Skin Cancer Risk in BRCA1/2 Mutation Carriers
abstract
Women with BRCA1/2 mutations have an elevated risk of breast and ovarian cancer. These patients and their clinicians are often concerned about their risk for other cancers, including skin cancer. Research evaluating the association between BRCA1/2 mutations and skin cancer is limited and has produced inconsistent results. Herein, we review the current literature on the risk of melanoma and non-melanoma skin cancers in BRCA1/2 mutation carriers. No studies have shown a statistically significant risk of melanoma in BRCA1 families. BRCA2 mutations have been linked to melanoma in large breast and ovarian cancer families, though a statistically significant elevated risk was reported in only one study. Five additional studies have shown some association between BRCA2 mutations and melanoma, while four studies did not find any association. With respect to non-melanoma skin cancers, studies have produced conflicting results. Given the current state of medical knowledge, there is insufficient evidence to warrant increased skin cancer surveillance of patients with a confirmed BRCA1/2 mutation or a family history of a BRCA1/2 mutation, in the absence of standard risk factors. Nonetheless, suspected BRCA1/2 mutation carriers should be counseled about skin cancer risks and may benefit from yearly full skin exams.
Very late recurrence (after more than 20 years) of epithelial ovarian carcinoma: case report and literature review
"Lifelong follow-up is critically important for ovarian cancer patients."
(Opinion - and clinical/research reporting)
abstract
PURPOSE:
To present a case of very late (more than 20 years) recurrence of epithelial ovarian carcinoma and to review the pertinent literature. We encountered a 50-year-old patient who, at the age of 22, underwent cytoreductive surgery and adjuvant chemotherapy for stage III serous ovarian carcinoma. She recurred after 28 years and underwent secondary surgery and chemotherapy.METHOD:
A PubMed search of the English literature containing the following key words: ovarian cancer, late recurrence, late relapse, late metastasis was performed.RESULTS:
Only five cases (including the present one) with recurrence after more than 20 years are so far on record. Of these, four patients were 33 years old or younger and had advanced stage at diagnosis. Time to recurrence ranged from 21 to 28 years. All patients had serous carcinoma and three had recurrence in lymph nodes.CONCLUSIONS:
Very late recurrence is an extremely rare event and may result from either regrowth of dormant tumor cells or from development of a new cancer. Lifelong follow-up is critically important for ovarian cancer patients.Future Oncology - Index: Themed Content: Minimizing morbidity in radiation oncology
Index
 Best of the Radiosurgery Society®
Scientific Meeting 2014: stereotactic radiosurgery/stereotactic body
radiotherapy treatment of extracranial and intracranial lesions |
Research Article
Chest
wall and rib irradiation and toxicities of early-stage lung cancer
patients treated with CyberKnife stereotactic body radiotherapy
|
Special Report
The promise of combining radiation therapy and immunotherapy: morbidity and toxicity
|
Review
Radiation oncology: physics advances that minimize morbidity
|
Radioprotective agents for radiation therapy: future trends
|
Radiobiological modifiers in clinical radiation oncology: current reality and future potential
|
The use of angiotensin II receptor antagonists to increase the efficacy of radiotherapy in cancer treatment
|
Radiogenomics: the search for genetic predictors of radiotherapy response
|
New ways to successfully target tumor vasculature in ovarian cancer
abstract
Purpose of review: The aim of this article was to review the
recent literature on potential therapeutic strategies for overcoming
resistance to antivascular endothelial growth factor drugs in ovarian
cancer.
Recent findings: Although clinical benefits of
antivascular endothelial growth factor therapy were observed in ovarian
cancer treatment trials, this use yielded only modest improvement in
progression-free survival and, with the exception of cediranib, no
effect on overall survival. Adaptive resistance and escape from
antiangiogenesis therapy is likely a multifactorial process, including
induction of hypoxia, vascular modulators, and immune response. New
drugs targeting the tumor vasculature or other components of the
surrounding microenvironment have shown promising results.
Summary: When to start and end antiangiogenesis therapy
and the choice of optimal treatment combinations remain controversial.
Further evaluation of personalized novel angiogenesis-based therapy is
warranted. Defining the critical interaction of these agents and
pathways and the appropriate predictive markers will become an
increasingly important objective for effective treatment.
Friday, December 19, 2014
Combining images and genetic data proves gene loss behind aggressive ovarian cancers - PTEN
Preclinical Efficacy for AKT Targeting in Clear Cell Carcinoma of the Ovary
abstract
The aim of this study was to determine the role of AKT as a therapeutic target in ovarian clear cell carcinoma (CCC), an aggressive, chemoresistant histological subtype of ovarian cancer. AKT activation was assessed by immunohistochemistry (IHC) using human tissue microarrays of primary ovarian cancers, comprised of both CCC and serous adenocarcinoma (SAC). The growth-inhibitory effect of AKT-specific targeting by, the small molecule inhibitor, perifosine was examined using ovarian CCC cell lines in vitro and in vivo. Finally, the activity of perifosine was examined using in CCC-derived tumors that had acquired resistance to anti-VEGF or chemotherapeutics like bevacizumab or cisplatin, respectively. Interestingly, AKT was frequently activated both in early-stage and advanced-stage CCCs.
Treatment of CCC cells with perifosine attenuated the activity of AKT targeted therapy for ovarian clear cell carcinoma. AKT-mTORC1 signaling, inhibited proliferation, and induced apoptosis. The effect of perifosine was more profound under conditions of high AKT activity compared to low AKT activity. Increased AKT activation and enhanced sensitivity to perifosine were observed in the context of cisplatin-resistant CCC. Treatment with perifosine concurrently with cisplatin significantly enhanced the anti-tumor effect of cisplatin. Moreover, perifosine showed significant anti-tumor activity in CCC-derived tumors that had acquired resistance to bevacizumab or cisplatin. Collectively, these data reveal that AKT is frequently activated in ovarian CCCs and is a promising therapeutic target in aggressive forms of ovarian cancer.
Implications: AKT-targeted therapy has value in a front-line setting as well as a second-line treatment for recurrent disease developing after platinum-based chemotherapy or bevacizumab treatment.
Interactions of Multitargeted Kinase Inhibitors and Nucleoside Drugs: Achilles Heel of Combination Therapy?
abstract (technical)
Multitargeted
tyrosine kinase inhibitors (TKI) axitinib, pazopanib, and sunitinib are
used to treat many solid tumors. Combination trials of TKIs with
gemcitabine, a nucleoside anticancer drug, in pancreas, renal, lung,
ovarian, and other malignancies resulted in little benefit to patients. ........An additional unwanted interaction may be reduced
FLT uptake in tumor tissues that could lead to aberrant conclusions
regarding tumor response.
fluorothymidine (FLT)
fluorothymidine (FLT)
Targeting those with decreased meaning and peace: a supportive care opportunity
abstract
PURPOSE:
To evaluate if an individual's level of meaning/peace (M/P) predicts various quality of life (QOL) and mental well-being measures. To identify targets that might enhance the overall spiritual well-being and QOL of ovarian cancer patients.METHODS:
Multi-site analysis of women with newly diagnosed stages II-IV ovarian, primary peritoneal, or fallopian tube cancer. Patients completed the following surveys: Functional Assessment of Chronic Illness Therapy-Ovarian (FACT-O), Functional Assessment of Chronic Illness Therapy-Spiritual (FACIT-Sp), Edmonton Symptom Assessment System (ESAS), Hospital Anxiety and Depression Scale (HADS), Templer's Death Anxiety Scale (DAS), Herth Hope Index (HHI), and Brief Multidimensional Measure of Religiousness/Spirituality (BMMRS). Linear regression models were created to examine the effect of M/P (FACIT-Sp) upon QOL, symptoms, and other measures of mental well-being. These models adjusted for the effect of site, race, age, stage, anaphylaxis to chemotherapy, and partner status as potential confounders.RESULTS:
This study enrolled 104 patients from three separate sites. After adjusting for potential confounders, it was found that higher M/P predicted better QOL (FACT-O) (p < 0.0001). Higher M/P also predicted decreased death anxiety, depression, and anxiety (p ≤ 0.005). Finally, higher M/P predicted increased hope and coping scores (p ≤ 0.0005).CONCLUSIONS:
Level of M/P is associated with several important mental and physical health states. This information may allow providers to identify patients at increased risk for mental/physical distress and may facilitate early referral to targeted psychotherapy interventions focused on improving patient QOL and decreasing anxiety and depression.Predictive factors for the presence of malignant transformation of pelvic endometriosis
abstract
OBJECTIVES:
To determine predictive factors for the presence of malignant transformation in ovarian endometriotic cysts.STUDY DESIGN:
This was an IRB approved, case control study analyzing patient data from 2004 to 2013. Pathology database records were searched to identify patients with benign endometrioma and ovarian carcinoma arising in the background of endometriosis. Inclusion criteria required each patient to have a preoperative diagnosis of adnexal mass and no other findings concerning for malignancy. Patient clinical records were queried for preoperative symptoms, serum CA125 levels and radiologic findings. Pathologic data were collected including histology, tumor grade and stage.RESULTS:
A total of 138 patients met inclusion criteria; 42 women with ovarian cancer arising in the background of endometriosis and 96 women with benign endometrioma. Women diagnosed with ovarian cancer were significantly older than women with endometriosis (53.6 vs. 39.2 years). There was no difference in presence of symptoms between the two groups. Women with malignant tumors were found to have significantly larger cysts (14cm vs. 7.5cm; p<0.0001) that were more often multilocular (45.7% vs. 12.2%; p<0.0001), and contained solid components (77.1% vs. 14.5%; p<0.0001). Among patients that were observed prior to surgery there was a significant difference in the change in size of the mass over time with 4.2cm increase for cases vs. 1.0cm increase for controls (p=0.02). Multiple logistic regression analysis indicated that for every 5 years increase in age there was an adjusted OR of 2.17 (p=0.003). An age of 49 years or greater had an 80.6% sensitivity (95% CI: 62.5-92.5%) and an 82.9% specificity (95% CI: 67.9-92.8%) for malignancy, and solid component on imaging had an adjusted OR of 23.7 (p<0.0001). Serum CA125 levels tended to be higher in patients with malignant tumors but did not reach statistical significance with a mean of 204.9 vs. 66.9 (p=0.1).CONCLUSIONS:
Significant predictors for malignant transformation of endometriosis include cyst characteristics and age. Women above the age of 49 with multilocular cysts and solid components are at high risk for malignant transformation of endometriosis. Serum CA125 level is not a significant predictor of malignant transformation.Wednesday, December 17, 2014
NIH complementary and integrative health agency gets new name (U.S.)
NCCIH
The National Institutes of Health agency with primary responsibility for research on promising health approaches that already are in use by the American public has a new name — the National Center for Complementary and Integrative Health (NCCIH).....
Searching for metastases in ovarian tissue before autotransplantation: a tailor-made approach
abstract
OBJECTIVE:
To exclude minimal residual disease in remaining ovarian tissue after harvesting the ovarian cortex for cryopreservation, by means of a tailor-made approach.DESIGN:
Retrospective case series.SETTING:
Hospital laboratory.PATIENT(S):
We evaluated the ovarian and tubal tissue from 47 cancer patients (breast cancer, [non-]Hodgkin lymphoma; osteo-, Ewing, myxoid lipo-, and oropharyngeal synovial sarcoma; cervical, rectal, and esophageal cancer), who had stored ovarian tissue for fertility preservation.INTERVENTION(S):
Immunohistochemistry (IHC) with tumor-related antibodies and genetic mutation analysis were performed to detect micrometastases by multiple sectioning at three levels of the paraffin-embedded formalin-fixed material. Molecular assays were performed with the use of tissue between these three levels of sectioning.MAIN OUTCOME MEASURE(S):
Detection of micrometastases in ovaries.RESULT(S):
We analyzed 847 ovarian slides to detect isolated tumor cells (ITCs) or micrometastases by IHC. In only one case (1/47) were ITCs detected in the fallopian tube. That patient had an intra-abdominal metastatic esophageal carcinoma. Additional DNA analyses of breast and rectal cancer, Ewing sarcoma, and human papilloma virus in cervical patients did not show evidence of micrometastases in the ovarian tissue.CONCLUSION(S):
The tailor-made approach consisted of patient-specific tumor markers which were used to search for ovarian micrometastases. We found evidence of metastatic disease within the fallopian tube of a patient with intraperitoneal metastatic esophageal adenocarcinoma.Survival outcome of stage I ovarian clear cell carcinoma with lympho-vascular space invasion
abstract
BACKGROUND:
The clinical impact of lympho-vascular space invasion (LVSI) in early-stage ovarian clear cell carcinoma (OCCC) is not well understood. Given the distinct tumor biology and survival patterns of OCCC, the significance of LVSI on survival outcome and treatment response was examined in OCCC.METHODS:
A multicenter study was conducted to examine stage IA-IC3 OCCC cases that underwent primary surgical staging including lymphadenectomy. LVSI status was determined from archived histopathology slides, correlated with clinico-pathological results, chemotherapy patterns, and survival outcomes.RESULTS:
LVSI was observed in 47 (20.3%) among 232 cases. In univariate analysis, LVSI was associated with older age (p=0.042), large tumor size (p=0.048), and stage IC (p=0.035). In survival analysis, LVSI was associated with decreased disease-free survival (DFS, 5-year rate, 70.6% versus 92.1%, p=0.0004) and overall survival (OS, 78.8% versus 93.3%, p=0.008) on univariate analysis. After controlling for age, tumor size, stage, and chemotherapy use, LVSI remained an independent prognostic factor for decreased survival outcomes (DFS, hazard ratio [HR] 4.35, 95% confidence interval [CI] 1.73-10.9, p=0.002; and OS, HR 4.73, 95%CI 1.60-14.0, p=0.015). Among 210 cases who received postoperative chemotherapy, while regimen type did not impact survival outcome regardless of LVSI status (DFS, p=0.63), the number of administered cycles showed a survival benefit towards ≥6cycles for patients with LVSI-positive tumors (DFS p=0.009, and OS p=0.016).CONCLUSION:
LVSI is an important marker to predict survival outcome of stage I OCCC. Regardless of chemotherapy type, patients with stage I OCCC showing LVSI may benefit from receiving postoperative chemotherapy.Surgical site infection after primary surgery for epithelial ovarian cancer: predictors and impact on survival
abstract
OBJECTIVE::
Surgical site infection (SSI) following epithelial ovarian cancer (EOC) primary surgery (PS) occurs in 10-15% of women. Perioperative factors associated with SSI and impact of SSI on survival were determined.METHODS::
EOC cases that underwent PS from 1/2/2003-12/30/2011 were retrospectively reviewed. SSIs were defined according to ACS NSQIP. Logistic regression models were fit to identify factors associated with SSI. Cox proportional hazards models were utilized to evaluate the association of patient and perioperative characteristics with overall survival (OS) and disease-free survival (DFS).RESULTS::
Among 888 cases, 96 (10.8%) developed SSI: 32 superficial, 2 deep, and 62 organ/space. Factors independently associated with superficial SSI were increasing BMI (odds ratio 1.41 [95% confidence interval, 1.12, 1.76] per 5kg/m2), increasing operative time (1.24 [1.02, 1.50] per hour), and advanced stage (III/IV) (10.22 [1.37, 76.20]). Factors independently associated with organ/space SSI were history of gastroesophageal reflux disease (2.13 [1.23, 3.71]), surgical complexity (intermediate 3.11 [1.02, 9.49]; high 8.07 [2.60, 25.09]; referent: low), and residual disease (RD) (measureable ≤1cm 1.77 [0.96, 3.27]; suboptimal >1cm (3.36 [1.48, 7.61]; referent: microscopic). Occurrence of superficial (hazard ratio 1.69 [1.12, 2.57]) or organ/space (1.46 [1.07, 2.00]) SSI was independently associated with worse OS. SSI occurrence was not independently associated with DFS.CONCLUSIONS::
SSI after PS is associated with decreased OS. Most risk factors for SSI are not modifiable. Alternative measures to lower rates of SSIs are needed as this may improve OS. Preoperative identification of SSI risk factors may assist in risk-assessment and operative planning.Challenges in managing genetic cancer risk: a long-term qualitative study of unaffected women carrying BRCA1/BRCA2 mutations
abstract
Purpose:
Women carrying BRCA1/BRCA2 germ-line mutations have an increased risk of developing breast/ovarian cancer. To minimize this risk, international guidelines recommend lifelong surveillance and preventive measures. This study explores the challenges that unaffected women genetically predisposed to breast/ovarian cancer face in managing their risk over time and the psychosocial processes behind these challenges
Methods:
Between 2011 and 2013, biographical qualitative interviews were conducted in Switzerland with 32 unaffected French- and Italian-speaking women carrying BRCA1/BRCA2 mutations. Their mutation status had been known for at least 3 years (mean, 6 years). Data were analyzed through constant comparative analysis using software for qualitative analysis.
Results:
From the time these women received their positive genetic test results, they were encouraged to follow medical guidelines. Meanwhile, their adherence to these guidelines was constantly questioned by their social and medical environments. As a result of these contradictory pressures, BRCA1/BRCA2 mutation carriers experienced a sense of disorientation about the most appropriate way of dealing with genetic risk.
Conclusion:
Given the contradictory attitudes of health-care professionals in caring for unaffected BRCA1/BRCA2 mutation carriers, there is an urgent need to educate physicians in dealing with genetically at-risk women and to promote a shared representation of this condition among them.
Clinical characteristics and outcomes of patients with stage I epithelial ovarian cancer compared to fallopian tube cancer
abstract
OBJECTIVE:
Compare clinical characteristics and survival between patients with stage I epithelial ovarian cancer and fallopian tube cancer.STUDY DESIGN:
We identified women with stage I epithelial ovarian cancer and fallopian tube cancer that underwent treatment between 2000 and 2010......RESULTS:
The study group consisted of 385 women with epithelial ovarian cancer and 43 with fallopian tube cancer. Patients with fallopian tube cancer had a higher rate of stage IA disease (65% vs. 48%; P = 0.02) and grade 3 tumors (60.4% vs. 30.9%; P < 0.001). Patients with fallopian tube cancer had a significantly higher rate of breast cancer (25.6% vs. 5.7%; P < 0.001) and BRCA 1 mutations (45.8% vs. 9.1% P < 0.001). There was no difference in the rates of platinum-based and paclitaxel chemotherapy between the groups. Women with fallopian tube cancer were more likely to have received six or more cycles of chemotherapy (58.1% vs. 44.1%; P = 0.02). The 5-year disease-free survival rates were 100% in women with fallopian tube cancer and 93% in patients with epithelial ovarian cancer (P = 0.04). The 5-year overall survival rates were 100% and 95% for fallopian tube cancer and epithelial ovarian cancer, respectively (P = 0.7).CONCLUSIONS:
We found a higher rate of stage IA, grade 3, and serous carcinoma in fallopian tube cancer. Women with fallopian tube cancer had a higher rate of breast cancer. There was no difference in overall survival between the groups.Positron Emission Tomography (PET) in Oncology
Free Full-Text
1.8.1. Ovarian Cancer
There is mounting evidence that FDG-PET/CT has an increasing role in the management of ovarian cancer, with its main indication to detect tumor recurrence in presence of rising CA-125 serum values and negative conventional imaging studies [93]. The benefits of the use of FDG-PET/CT in these settings has been reported several times in the literature [94,95], with a sensitivity of more than 90% in detecting occult metastases. In the study of Zimny et al., FDG-PET/CT preceded the conventional diagnosis by a median of 6 months in patients judged clinically free of disease. Menzel et al. suggest that a PET indication is worthwhile at CA 125 levels of approximately 30 U/mL [96]. A more recent prospective multi-center, cohort study (90 patients) confirmed the impact of FDG-PET/CT in suspected recurrent ovarian cancer, which affected disease management decisions in 60% of the cases (in 49% with a high, in 11% with a medium clinical impact) with a much higher detection rate compared to conventional imaging [97].For the characterization of asymptomatic adnexal findings, FDG-PET/CT has no place due to lack of sensitivity [98], and MRI remains the best imaging modality choice.
For the initial staging of ovarian cancer, FDG-PET/CT is not routinely used. Nevertheless, some publications noticed that it could be interesting in advanced epithelial ovarian cancer, in particular for the detection of supradiaphragmatic lymph node metastases like parasternal lymph nodes, with better accuracy than conventional CT (detection rate: 67% vs. 33%) [99]. However, increased mediastinal FDG uptake was not shown to play a significant prognostic role, while complete cytoreduction did [100]. For the initial preoperative staging of ovarian cancer, FDG-PET/CT may be superior compared to CT alone [101,102], but some publications also observed limits, as De Iaco et al., who reported a sensitivity and specificity of 78 and 68% respectively, with a high rate of false negative results in lesions <5 mm such as found in presence of peritoneal carcinomatosis [103].
However, conflicting results have been reported on the sensitivity of FDG-PET/CT scan in detecting peritoneal carcinomatosis; Turlakow, Suzuki and Kim reported higher diagnostic accuracy of FDG-PET/CT than CeCT in this settings, with a sensitivity and specificity for FDG-PET/CT of 67%–92.2% and 90%–94% respectively, as compared to 22%–88.5% and 65%–77% respectively for CeCT [104,105,106]. The sensitivity of FDG-PET/CT proved also similar to that of conventional MRI, and even better for detecting small peritoneal lesions (<2 cm) in patients with recurrent ovarian cancer [107]. However, FDG-PET/CT has limits, in particular for the detection of small peritoneal implants (<5 mm) because of the limited PET resolution, and surgical staging remains the gold standard [108]. The good performances of FDG-PET/CT in detecting peritoneal carcinomatosis lead to interesting information for optimizing patient selection for cytoreductive surgery in recurrent ovarian cancer; recently, Ebina et al. observed that FDG-PET/CT led to a change in management plan in 58.4% in that case, with a total number of patients in whom cytoreductive surgery was selected as the treatment of choice increased from 12 to 35 according to FDG-PET-CT results [109]. In the preoperative management, FDG-PET/CT is also able to detect distant metastases (25/95 patients upstaged from FIGO stage III to stage IV by FDG-PET/CT in a recent study [110]. However, upward stage migration did not worsen the prognosis of stage III patients, and in advanced ovarian cancer, the only prognostic factor that retained a significant prognostic value is the quality of response to cytoreductive therapy. Another study proposed FDG-PET/CT criteria such as FDG-PET/CT stage IV, pleural exudates, and PET-positive large bowel mesentery implants, which were statistically significant in the prognosis univariate analysis to guide the administration of neo-adjuvant chemotherapy in advanced ovarian cancer, but, once again, incomplete tumor debulking was the only statistically significant independent prognostic variable using multivariate analysis (p = 0.0001) [111]. Other prognostic factors like MTV or TGL may be interesting, but more data are needed at this time to confirm that [112].
- See more at: http://www.mdpi.com/2072-6694/6/4/1821/htm#sthash.MzNWUkeA.dpuf
Dynamic Changes in Numbers and Properties of Circulating Tumor Cells and Their Potential Applications | HTML
Free Full-Text
Abstract
: Circulating tumor cells (CTCs) can be detected in the blood of different types of early or advanced cancer using immunology-based assays or nucleic acid methods. The detection and quantification of CTCs has significant clinical utility in the prognosis of metastatic breast, prostate, and colorectal cancers. CTCs are a heterogeneous population of cells and often different from those of their respective primary tumor. Understanding the biology of CTCs may provide useful predictive information for the selection of the most appropriate treatment. Therefore, CTC detection and characterization could become a valuable tool to refine prognosis and serve as a “real-time biopsy” and has the potential to guide precision cancer therapies, monitor cancer treatment, and investigate the process of metastasis. - See more at: http://www.mdpi.com/2072-6694/6/4/2369/htm#sthash.UvsIAwMW.dpufAbstract
: Circulating tumor cells (CTCs) can be detected in the blood of different types of early or advanced cancer using immunology-based assays or nucleic acid methods. The detection and quantification of CTCs has significant clinical utility in the prognosis of metastatic breast, prostate, and colorectal cancers. CTCs are a heterogeneous population of cells and often different from those of their respective primary tumor. Understanding the biology of CTCs may provide useful predictive information for the selection of the most appropriate treatment. Therefore, CTC detection and characterization could become a valuable tool to refine prognosis and serve as a “real-time biopsy” and has the potential to guide precision cancer therapies, monitor cancer treatment, and investigate the process of metastasis. - See more at: http://www.mdpi.com/2072-6694/6/4/2369/htm#sthash.UvsIAwMW.dpufAbstract
: Circulating tumor cells (CTCs) can be detected in the blood of different types of early or advanced cancer using immunology-based assays or nucleic acid methods. The detection and quantification of CTCs has significant clinical utility in the prognosis of metastatic breast, prostate, and colorectal cancers. CTCs are a heterogeneous population of cells and often different from those of their respective primary tumor. Understanding the biology of CTCs may provide useful predictive information for the selection of the most appropriate treatment. Therefore, CTC detection and characterization could become a valuable tool to refine prognosis and serve as a “real-time biopsy” and has the potential to guide precision cancer therapies, monitor cancer treatment, and investigate the process of metastasis. - See more at: http://www.mdpi.com/2072-6694/6/4/2369/htm#sthash.UvsIAwMW.dpufAbstract
: Circulating tumor cells (CTCs) can be detected in the blood of different types of early or advanced cancer using immunology-based assays or nucleic acid methods. The detection and quantification of CTCs has significant clinical utility in the prognosis of metastatic breast, prostate, and colorectal cancers. CTCs are a heterogeneous population of cells and often different from those of their respective primary tumor. Understanding the biology of CTCs may provide useful predictive information for the selection of the most appropriate treatment. Therefore, CTC detection and characterization could become a valuable tool to refine prognosis and serve as a “real-time biopsy” and has the potential to guide precision cancer therapies, monitor cancer treatment, and investigate the process of metastasis. - See more at: http://www.mdpi.com/2072-6694/6/4/2369/htm#sthash.UvsIAwMW.dpufTuesday, December 16, 2014
Hereditary Cancer-Associated Mutations in Women Diagnosed with Two Primary Cancers: An Opportunity to Identify Hereditary Cancer Syndromes after the First Cancer Diagnosis
FullText Myriad Genetic Laboratories, Inc., Salt Lake City, Utah, USA
Results: Among women with both breast and ovarian cancer, 22.4% (2,237/9,982) had a BRCA1 or BRCA2 mutation. Among women with both colorectal and ovarian cancer, 28.1% (264/941) had a mutation associated with LS. In 66.6% of BRCA1 or BRCA2 mutation carriers and in 58.3% of LS mutation carriers, >5 years passed between the cancer diagnoses.......
Table 2. Interval between the first and the second cancer diagnosis in patients with HBOC
Table 4. Interval between first and second cancer diagnoses in patients with LS
What really matters in end-of-life discussions? Perspectives of patients in hospital with serious illness and their families
open access
Interpretation: We identified elements of goals-of-care discussions that are most important to older adult patients in hospital with serious illness and their family members. We found that guideline-recommended elements of goals-of-care discussions are not often addressed by health care providers. Our results can inform interventions to improve the determination of goals of care in the hospital setting.
Lynch Syndrome Caused by Germline PMS2 Mutations: Delineating the Cancer Risk
abstract
Significant SIRs were observed for cancers of the small bowel, ovaries, breast, and renal pelvis.
Monday, December 15, 2014
(Lynch Syndrome etc) ASCO CPG Endorsement of the Familial Risk–Colorectal Cancer: ESMO CPG
open access
Hereditary Colorectal Cancer Syndromes: American Society of Clinical Oncology Clinical Practice Guideline Endorsement of the Familial Risk–Colorectal Cancer: European Society for Medical Oncology Clinical Practice Guidelines
Lynch syndrome
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Colon and rectum: Colonoscopy every 1 to 2 years, starting at age 20 to 25 or 5 years before the youngest case in the family. No upper limit is established.
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Endometrium and ovary: Gynecological examination, pelvic ultrasound (not CA-125), and aspiration biopsy every year, from age 30 to 35 years. Consider prophylactic hysterectomy and salpingoophorectomy when childbearing is completed.
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Gastric cancer: For gastric cancer, the search for the presence of Helicobacter pylori and subsequent eradication is recommended in mutation carriers. In case of a high incidence of gastric cancer in some populations, some experts recommend upper GI endoscopy every 1 to 3 years.
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Other Lynch-associated cancers: Surveillance is not recommended due to the low sensitivity and specificity. (Although there are insufficient data supporting surveillance for other target organs, it may be considered in the context of family history.)....... Unlike CRC, data to support the effectiveness of transvaginal ultrasound and endometrial biopsy for gynecologic surveillance are lacking, and only surgical removal of the uterus and ovaries (fallopian tubes???) has been shown to reduce incidence of endometrial and ovarian cancers.10 Individuals with LS also have an elevated risk of developing other cancers, specifically tumors of the urinary tract (lifetime risk, 5% to 12%), small intestine, ovary (lifetime risk, 4% to 12%), stomach (lifetime risk, 8% to 10%), pancreas (lifetime risk, 4%), biliary tract, brain, and skin.11,12 Comparisons of phenotype according to MMR gene mutation have shown that MLH1-mutation carriers tend to develop CRC at younger ages, whereas MSH2 carriers seem to be at higher risk for extracolonic cancers, and for women with MSH6 mutations, the risk for endometrial cancer may surpass the lifetime CRC risk.13–15 In contrast, the risks for CRC and endometrial cancer seem to be lower among individuals with mutations in PMS2 (15% to 20%) compared with carriers of other MMR gene mutations.16........
Saturday, December 13, 2014
Commentary on ‘Performance of ultrasound as a second line test to serum CA125 in ovarian cancer screening’
Commentary - open access
Conclusions
The
last 50 years have seen a sea change in ideas regarding the origins of
ovarian cancer, its natural history and the best ways of improving
mortality. Despite advances in chemotherapy regimens and targeted
therapies there has been little change in the prognosis for women with
advanced disease. Hope therefore rests with the ability of ovarian
cancer screening strategies to shift the burden of disease to earlier
stages, which may translate to better clinical outcomes and reduced
mortality. Multimodal screening and ultrasound-based approaches have
been shown to be sensitive and specific for detecting ovarian cancer but
whether these in themselves will provide sufficient lead time to change
the course of the disease remains to be shown. Ultimately success will
depend on the continued momentum of the multiple international and
multidisciplinary collaborations forged to ensure that research will
continue for better biomarkers that can be translated into clinical
interventions. It is imperative that clinicians and researchers continue
to engage the public and capitalise on the enthusiasm embodied by the
high compliance rates seen in the screening studies to work towards
reducing mortality from ovarian cancer.
Thursday, December 11, 2014
Enhanced recovery pathways in gynecologic oncology
abstract
Highlights
- •
- Enhanced Recovery Pathways (ERP) are safe for patients undergoing complex gynecologic oncology operations, including colonic resection.
- •
- Incorporation of a comprehensive ERP is associated with reduced length of stay, excellent patient satisfaction, and lower costs.
- •
- Successful implementation of ERP requires standardization and cooperation within the care team.
Abstract
Objective
Many
commonplace perioperative practices are lacking in scientific evidence
and may interfere with the goal of optimizing patient recovery.
Individual components of perioperative care have therefore been
scrutinized, resulting in the creation of so-called “enhanced recovery”
pathways (ERP), with the goal of hastening surgical recovery through
attenuation of the stress response. In this review we examine the
evidence for ERP in gynecologic oncology using data from our specialty
and general surgery.
Methods
We
performed a systematic literature search on ERP in gynecologic oncology
in June 2014 using PubMed/MEDLINE, EMBASE, and The Cochrane Library. All
study types were included. References were hand reviewed to ensure
completeness. The Enhanced Recovery After Surgery (ERAS) Society was
contacted to identify any unpublished protocols.
Results
Seven
investigations were identified that examined the role of ERP in
gynecologic oncology. Common interventions included allowing oral intake
of fluids up to 2 hours before induction of anesthesia, solids up to
6 hours before anesthesia, carbohydrate supplementation, intra- and
postoperative euvolemia, aggressive nausea/vomiting prophylaxis, and
oral nutrition and ambulation the day of surgery. In addition, bowel
preparations, the NPO after midnight rule, nasogastric tubes, and
intravenous opioids were discontinued. While no randomized data are
available in gynecologic oncology, significant improvements in patient
satisfaction, length of stay (up to 4 days), and cost (up to $7600 in
savings per patient) were observed in ERP cohorts compared to historical
controls. Morbidity, mortality, and readmission rates were no different
between groups.
Conclusion
Enhanced
recovery is a safe perioperative management strategy for patients
undergoing surgery for gynecologic malignancies, reduces length of stay
and cost, and is considered standard of care at a growing number of
institutions. Our specialty would benefit from a formalized ERP such as
ERAS which audits compliance to protocol care elements to optimize
patient outcomes and value.
Old drug, new trick: Repurposing metformin for gynecologic cancers?
abstract
Highlights
- •
- We summarize the molecular mechanisms of action mediating metformin's protective effect in cancer.
- •
- Review the preclinical and epidemiological evidences for metformin's potential role in gynecological cancers.
- •
- Description of ongoing prospective testing of metformin in gynecologic cancers and future directions.
Abstract
Objective
There
is increasing pre-clinical and clinical evidence that metformin, a
commonly used diabetes medication, has a protective effect in cancer.
The aim of this review is to discuss metformin's anti-cancer molecular
mechanisms of action and to summarize the current literature
demonstrating metformin's potential in gynecologic cancer prevention and
treatment.
Methods
A PubMed
search was conducted combining the keywords “metformin” with “neoplasm”,
“uterine neoplasms”, “ovarian neoplasms”, and “uterine cervical
neoplasms”. Studies published in English between 1994 and 2014 were
included.
Results
Pre-clinical
studies in endometrial, ovarian, and cervical cancer suggest that
metformin inhibits the growth of cancer cells. The primary molecular
mechanism mediating this effect appears to be the activation of
AMP-activated protein kinase (AMPK) and the subsequent inhibition of
mammalian targets of rapamycin (mTOR). The pre-clinical findings are
augmented by clinical studies indicating that metformin use is
associated with a reduced risk of cancer and improved survival in
diabetic women with ovarian and endometrial cancers. No clinical
analyses have evaluated metformin use and cervical cancer. Overall, the
data showing a favorable effect of metformin is strongest for
endometrial and ovarian cancer and prospective clinical testing is
ongoing in these two malignancies.
Conclusions
Numerous
clinical studies have reported an association between metformin use by
diabetic patients and improved outcomes in gynecologic cancers. In
addition, pre-clinical reports have identified plausible biological
mechanisms to explain the molecular mechanism of action of metformin in
cancer. However, the most important question remains unanswered: Will
metformin be effective against cancer in patients without diabetes?
Until this question is answered with prospective clinical testing, the
role of metformin in the treatment or prevention of gynecologic
malignancies remains theoretical and the clinical use of metformin as a
cancer therapeutic is experimental.
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