- •Women were satisfied with their decision to undergo robotic surgery.
- •General health, symptom burden, and sexual function returned to baseline quickly after robotic surgery.
Saturday, August 01, 2015
BRCA Mutations, DNA Repair Deficiency and Ovarian Aging
open access
..... We find that BRCA mutations negatively affect ovarian reserve based on convincing evidence from in vitro and in vivo evidence and prospective studies. Because decline in the function of the intact gene occurs at an earlier age, women with BRCA1 mutations exhibit accelerated ovarian aging unlike those with BRCA2 mutations. However, because of the still robust function of the intact allele in younger women and due to masking of most severe cases by prophylactic oophorectomy
or cancer, it is less likely to see an effect of BRCA mutations on fertility until later in
reproductive age......
Cellular and molecular processes in ovarian cancer metastasis
abstract
Ovarian cancer is the most lethal gynecological malignancy. It is usually diagnosed at a late stage, with a 5-year survival rate of less than 30%. The majority of ovarian cancer cases are diagnosed after tumors have widely spread within the peritoneal cavity, limiting the effectiveness of debulking surgery and chemotherapy. Owing to a substantially lower survival rate at late stages of disease than at earlier stages, the major cause of ovarian cancer deaths is believed to be therapy-resistant metastasis3. Although metastasis plays a crucial role in promoting ovarian tumor progression and decreasing patient survival rates, the underlying mechanisms of ovarian cancer spread have yet to be thoroughly explored. For many years, researchers have believed that ovarian cancer metastasizes via a passive mechanism by which ovarian cancer cells are shed from the primary tumor and carried by the physiological movement of peritoneal fluid to the peritoneum and omentum. However, the recent discovery of hematogenous metastasis of ovarian cancer to the omentum via circulating tumor cells instigated rethinking of the mode of ovarian cancer metastasis and importance of the "seed and soil" hypothesis for ovarian cancer metastasis. In this review, we discuss the possible mechanisms by which ovarian cancer cells metastasize from the primary tumor to the omentum, the cross-talk signaling events between ovarian cancer cells and various stromal cells that play crucial roles in ovarian cancer metastasis, and the possible clinical implications of these findings in the management of this deadly, highly metastatic disease.
Trends & Analysis of Cancer Incidence for Common Male & Female Cancers (Pakistan)
abstract
Trends and Analysis of Cancer Incidence for Common Male and Female Cancers in the Population of Punjab Province of Pakistan during 1984 to 2014.
BACKGROUND:
The Pakistan Atomic Energy Commission Cancer Registry (PAECCR) program has made availability of a common cancer incidence database possible in Pakistan. The cancer incidence data from nuclear medicine and oncology institutes were gathered and presented.MATERIALS AND METHODS:
The cancer incidence data for the last 30 years (1984-2014) are included to describe a data set of male and female patients. The data analysis concerning occurrence, trends of common cancers in male and female patients, stage-wise distribution, and mortality/follow-up cases is also incorporated for the last 10 years (2004-2014).RESULTS:
The total population of provincial capital Lahore is 9,800,000. The total number of cancer cases was 80,390 (males 32,156, females 48,134). The crude incidence rates in PAECCR areas were 580.8/105 during 2010 to 885.4/105 in 2014 (males 354.1/105, females 530.1/105). The cancer incidence rates for head and neck (15.70%), brain tumors (10.5%), and non-Hodgkin lymphoma (NHL, 9.53%) were found to be the highest in male patients, whereas breast cancer (46.7%), ovary tumors (6.80%),Effect of Previous Chemotherapy on the Quality of Cryopreserved Human Ovarian Tissue In Vitro.
abstract
BACKGROUND:
Cryopreservation of ovarian tissue has been widely accepted as an option for fertility preservation among cancer patients. Some patients are exposed to chemotherapy prior to ovarian tissue cryopreservation. Consequently, assessment of the developmental capacity of human ovarian tissue after chemotherapy is of primary importance.MATERIALS:
In order to study the impact of previous chemotherapy on in vitro development and viability of ovarian follicles, quality control samples from 34 female cancer patients at median age of 15 years (range 1‒35),Targeting c-MYC in platinum-resistant ovarian cancer
Friday, July 31, 2015
Hereditary Ovarian Cancer: Not Only BRCA 1 and 2 Genes
2015 open access
Abstract
More than one-fifth of ovarian tumors have hereditary susceptibility and, in about 65–85% of these cases, the genetic abnormality is a germline mutation in BRCA genes. Nevertheless, several other suppressor genes and oncogenes have been associated with hereditary ovarian cancers, including the mismatch repair (MMR) genes in Lynch syndrome, the tumor suppressor gene, TP53, in the Li-Fraumeni syndrome, and several other genes involved in the double-strand breaks repair system, such as CHEK2, RAD51, BRIP1, and PALB2. The study of genetic discriminators and deregulated pathways involved in hereditary ovarian syndromes is relevant for the future development of molecular diagnostic strategies and targeted therapeutic approaches. The recent development and implementation of next-generation sequencing technologies have provided the opportunity to simultaneously analyze multiple cancer susceptibility genes, reduce the delay and costs, and optimize the molecular diagnosis of hereditary tumors. Particularly, the identification of mutations in ovarian cancer susceptibility genes in healthy women may result in a more personalized cancer risk management with tailored clinical and radiological surveillance, chemopreventive approaches, and/or prophylactic surgeries. On the other hand, for ovarian cancer patients, the identification of mutations may provide potential targets for biologic agents and guide treatment decision-making.
1. Introduction
2. Clinical, Histopathological, and Molecular Features of Ovarian Cancer
3. Mismatch Repair Genes and Lynch Syndrome
4. TP53 and Li-Fraumeni Syndrome
5. Genes Involved in Double-Strand Breaks Repair
6. Next-Generation Sequencing with Multigene Panels
7. Conclusions
.....The centralization of genetic testing enables the improvement of access and quality of testing and allows for the creation of a more comprehensive database for research, guiding evidence-based management recommendations [89–91].
Call for Abstracts & Surgical Films: SGO 2015
2016
The 2016 SGO International Program will emphasize global gynecologic cancer epidemiology. Our goals are to identify geographic variations in the worldwide gynecologic cancer incidence with a particular emphasis on the burden of gynecologic cancers in low- and middle-income countries, the challenges of public health reporting, and examples of successful models for the development and implementation of reliable and accurate cancer registries.
The key concepts for presentation consideration include:
- Epidemiology
- Regional demographics and trends
- Treatment in developing countries
- Challenges in public health and data ascertainment
- Screening challenges
- Breast cancer
Thursday, July 30, 2015
Impact of Age and Primary Disease Site on Outcome in Women With Low-Grade Serous Carcinoma of the Ovary or Peritoneum
abstract
Impact of Age and Primary Disease Site on Outcome in Women With Low-Grade Serous Carcinoma of the Ovary or Peritoneum: Results of a Large Single-Institution Registry of a Rare Tumor
Purpose Low-grade
serous carcinoma of the ovary (LGSOC) or peritoneum (LGSPC) is a rare
subtype of ovarian or peritoneal cancer characterized
by young age at diagnosis and relative
resistance to chemotherapy. The purpose of this study is to report our
updated experience
with women diagnosed with LGSOC or LGSPC to
assess the validity of our original observations.
Patients and Methods
Eligibility criteria for patients from our database were: stage I to IV
LGSOC or LGSPC, original diagnosis before January
2012, and adequate clinical information. All
patients were included in progression-free survival, overall survival,
and multivariable
Cox regression analyses. A subset analysis was
performed among patients with stage II to IV low-grade serous carcinoma
treated
with primary surgery followed by platinum-based
chemotherapy.
Epidemiology in ovarian carcinoma: Lessons from autopsy
abstract
Highlights
- •
- Autopsy data challenges epidemiologic knowledge regarding incidence and prevalence of ovarian carcinoma.
- •
- Previous epidemiological data overestimate incidence because up to 10% of carcinomas in the ovary were metastases from other primary sites.
- •
- In 16% of autopsies, ovarian carcinoma in its final stage was first diagnosed by autopsy.
Objective
We challenge epidemiologic knowledge regarding ovarian carcinoma (OC) by bridging the gap between clinical and autopsy data.
Methods
Autopsy
reports, histological slides and clinical files from 660 patients in
whom OC was diagnosed from 1975-2005 were studied (autopsy cohort,
n = 233; Clinical Cancer Registry from the local gyneco-oncologic
center, n = 427).
Results
Out of
the autopsy cohort, we identified four distinct subgroups of patients:
1) OC was diagnosed before autopsy, n = 156 (67.0%). 2) OC was an
incidental finding, n = 16 (6.8%). 3) The ovarian tumors were not
primary OC but rather metastases from other primary tumors; this revised
diagnosis was first made by using current histopathological
knowledge/techniques, n = 24 (10.3%). 4) Death was directly due to OC in
its final stage and OC was first diagnosed by autopsy, n = 37 (15.9%);
when these cases were added to the Clinical Cancer Registry to an
adjusted OC incidence model, the autopsy cases comprised 8.8% of the
adjusted cohort and almost doubled the percentage of oldest patients
(≥ 80 years at diagnosis) from 4.9% to 9.3% (p = 0.013).
Conclusions
Epidemiological
data from the 1970s-1990s may overestimate true incidence because up to
10% of carcinomas in the ovary were not properly classified. Patients
who were first diagnosed with OC by autopsy comprise a distinct
subgroup. These are patients who have not been seen by specialized
oncologists and thus play no role in their perception of the disease.
Nevertheless, these cases have impact on prevalence and incidence data
of OC and in an era of reduced autopsy rates will probably be
overlooked.
Improvement in quality of life after robotic surgery results in patient satisfaction
abstract
Highlights
Background
There are well-described benefits to minimally invasive surgery including decreased blood loss, shorter hospital-stay, and faster recovery. The role of robotic surgery in gynecologic oncology has become increasingly prominent; however limited data are available on quality of life (QOL) after robotic surgery.Methods
In this prospective, IRB-approved study, women scheduled for robotic surgery for a gynecologic indication between May 2008 and February 2012 completed validated QOL measures at baseline, 6 weeks (6 wk), and 4 months postoperative (4 mo).Outcome of neoadjuvant chemotherapy in BRCA1/2 mutation positive women with advanced stage Müllerian cancer
abstract
Highlights
- •Patients with germline BRCA mutations had improved outcomes with NAC compared to patients with unknown BRCA status.
- •The outcomes of NAC in BRCA mutation positive patients were more favorable than the outcomes reported in the literature.
- •This is the first study evaluating the outcome of NAC in BRCA mutation positive patients with advanced-stage mullerian cancer.
Objectives
To investigate whether patients with germline BRCA1/2 mutations who received neoadjuvant chemotherapy (NAC) for advanced stage Mullerian cancer (MC) have an improved outcome compared to patients who did not undergo genetic testing.Methods
Three hundred and two patients who received NAC for stage III-IV MC were identified from a multi-institutional study involving Cleveland Clinic and Brigham and Women’s Hospital for 2000–2014 and 2010–2014 respectively. Patients were divided into 3 cohorts: patients with germline BRCA 1/2 mutations (BRCA_mut+; N = 30), patients with no genetic testing (BRCA_unk; N = 166) and patients with negative genetic testing (BRCA mut-, N = 106).Results
There were no differences in the clinical characteristics and rates of complete cytoreduction and bowel resection between the three groups. BRCA_mut + had longer PFS compared to BRCA_unk and BRCA_mut- (19.1 vs. 15.1 vs. 15.7 months respectively. However, this difference was not statistically significant (p = 0.48). Patients with BRCA 2 mutation had non-significant trend toward longer PFS compared to patients with unknown BRCA or BRCA 1 mutation (20.2 vs. 15.1 vs. 14.8 months respectively, p = 0.58). BRCA-mut + and BRCA_mut-had longer overall survivals (OS) compared to BRCA_unk patients (50.5 vs. 54.1 vs. 36.5 months respectively, p = 0.009). In multivariable analyses, controlling for age, stage and complete cytoreduction, BRCA_mut_unk was associated with worse PFS (HR 1.44, 95% CI 1.01-2.05, p = 0.045) and OS (HR 2.67, 95% CI 1.33-5.36, p = 0.006).Conclusions
Patients with germline BRCA mutations had improved outcomes with NAC compared to patients with unknown BRCA status. These outcomes were more favorable compared to the outcome of NAC in prior studies.Ascites predicts treatment benefit of bevacizumab in front-line therapy of advanced epithelial ovarian, fallopian tube and peritoneal cancers: An NRG Oncology/GOG study
Abstract
Highlights
- •We analyzed data from GOG 0218 to determine if ascites predicts response to bevacizumab.
- •Ascites was shown to be a negative prognostic factor in epithelial ovarian cancers.
- •Ascites is a significant clinical factor that may predict response to bevacizumab.
Objectives
Predictive factors for efficacy of bevacizumab in advanced ovarian cancer have remained elusive. We investigated ascites both as a prognostic factor and as a predictor of efficacy for bevacizumab.Methods
Using data from GOG 0218, patients receiving cytotoxic therapy plus concurrent and maintenance bevacizumab were compared to those receiving cytotoxic therapy plus placebo. The presence of ascites was determined prospectively. Chi-square and Wilcoxon–Mann–Whitney tests compared baseline variables between subgroups. Survival was estimated by Kaplan–Meier method, and Cox proportional hazard models were used to evaluate independent prognostic factors and estimate their covariate-adjusted effects on survival.Results
Treatment arms were balanced with respect to ascites and other prognostic factors. Overall, 886 (80%) women had ascites, 221 (20%) did not.Wednesday, July 29, 2015
Postoperative hormone replacement therapy for epithelial ovarian cancer patients: a systematic review and meta-analysis - Gynecologic Oncology
abstract
Highlights
- •This is the first meta-analysis on the effect of HRT on prognosis and recurrence of EOC survivors.
- •Postoperative HRT use is not associated with poorer clinical outcomes of EOC patients.
Background
. Hormone replacement therapy (HRT) has been proven highly effective for menopausal symptoms caused by radical surgery. However, the impact of postoperative HRT on the clinical outcomes of patients previously treated for epithelial ovarian cancer (EOC) remains unclear.Objective
. To determine whether postoperative HRT use has any positive or negative impacts on prognosis and recurrence among EOC survivors.Methods
. Studies that provided an assessment of postoperative HRT use and prognosis or recurrence in EOC patients were included for analysis. Two reviewers independently evaluated the eligibility of identified studies and abstracted the data. A fixed effects model was used to pool study-specific estimates of hazard ratios (HRs) or relative risks (RRs) with 95% confidence intervals (CIs).Results
. Two randomized controlled trials (RCTs) and four cohort studies included 419 EOC survivors who used HRT and 1,029 non-users. The aggregated HR of overall survival (OS) suggested that HRT use after surgery for EOC had a favorable impact on OS (HR = 0.69, 95% CI: 0.61–0.79), but when these studies were categorized into cohort study and RCT subgroups, not all of them demonstrated positive results (HR = 0.63, 95% CI: 0.49–0.81 and HR = 1.03, 95% CI: 0.58–1.83, respectively). The meta-analysis of EOC recurrence of three available studies demonstrated that postoperative HRT use was not associated with an increased risk of recurrence in EOC survivors (RR = 0.83, 95% CI: 0.64–1.07). This pattern also emerged in the subgroup analysis for the stage and type of HRT.Conclusions
. In EOC patients, postoperative HRT does not have a negative effect on overall survival and tumor recurrence. However, well-designed and large-scale RCTs are needed to verify this relationship in the future.Setting the bar: compliance with ovarian cancer quality indicators at a NCI-designated Comprehensive Cancer Center
abstract
Highlights
- •Appropriate quality indicator thresholds must take into account our complex patients
- •Complete surgical staging and timely administration of chemotherapy warrant attention
- •Existing perioperative quality measures demonstrate excellent compliance
Objectives
Ovarian cancer quality measures are being developed to improve health care delivery and outcomes. Our objective is to evaluate compliance with 8 quality indicators proposed by the Society of Gynecologic Oncology.Methods
Review of 123 ovarian cancer patients who underwent primary surgical staging/cytoreduction and chemotherapy from 2010–2012 was undertaken. Medical records were reviewed, and descriptive statistics were performed to determine compliance.Results
A timely operative report documenting residual disease was dictated for 121/123 (98.4%) patients. Complete surgical staging was performed in 33/55 (60.0%) stage I-IIIB patients, with lymphadenectomy most frequently omitted. For optimally debulked stage III patients, 52/56 (92.9%) were offered intraperitoneal chemotherapy. Ultimately, 29/56 (51.8%) received this route and 19/56 (33.9%) within 42 days (range 18–48, median 40 days). Clinical trial randomization and co-morbidities accounted for most cases of non-compliance. All 105 patients for whom chemotherapy was indicated received platin/taxane therapy, and 79/105 (75.2%) within 42 days (range 4–82, median 37 days). Venous thromboembolism prophylaxis was provided mechanically in 122/123 (99.2%) and pharmacologically in 99/123 (80.5%) patients within 24 hours of surgery. Prophylactic parenteral antibiotics were administered within 60 minutes of cytoreduction in 119/123 (96.7%) and discontinued within 24 hours after surgery in 120/123 (97.6%) cases.Conclusions
Compliance with strict definitions of ovarian cancer quality indicators varies depending on the care delivered and documentation of that care. Increased attention to comprehensive surgical staging and timely initiation of chemotherapy appears warranted. With the move toward value-based payment models, quality indicators will play a significant role in health care delivery.Biobank consent models – are we moving toward increased participant engagement in biobanking?
open access
Abstract: Engagement, involvement, and active participation are buzzwords used in today's ethical debate on research biobanking. There are a variety of context-sensitive governance frameworks for research biobanks. However, many biobanks, especially large-scale population-based ones, seem to endorse a framework of broad consent, participation with minimal or no ongoing engagement, and no return of results. An alternative vision of involvement and active participation in this type of research has become increasingly visible in the literature. The problem, seen from the biobankers' perspective, is that the alternative vision might be costly, cumbersome, and risky, while the prevailing system for governance will maximize the scientific value of the biobank with minimal ethical, legal, and social efforts. Therefore, solid and convincing arguments are needed to determine if biobank institutions should take a radical step toward more ongoing engagement and donor involvement. In this paper, we review the arguments found in articles addressing dynamic consent, participatory research, reciprocity, and participant engagement in biobank research. We identify four core ideas on which the arguments for increased involvement are based. The strength of the arguments are then analyzed. We conclude that despite challenges with increased engagement, there seem to be substantial reasons to increase participant engagement in biobanking.
Keywords: biobank ethics, participatory research, dynamic consent, reciprocity
Download Article [PDF]
Doctors busy prolonging life have lost sight of end of life care - audio (25 min)
CBC Radio
Oncologist Atul Gawande believes doctors spend so much
time helping people live longer, they've neglected how to improve the
quality of life at the end. (Tim-Llewellyn)
Listen 24:59
The Dr. Henry T. Lynch Symposium: Advances in Hereditary Cancer Sept 2015
announcement
The Dr. Henry T. Lynch Symposium: Advances in Hereditary Cancer
Creighton University Health Sciences Continuing Education
Thursday, September 17, 2015 at 7:00 AM - Friday, September 18, 2015 at 5:00 PM (CDT) Omaha, NE
Non-genetic cancer mechanism found - Akt pathway (Oncogene)
Cancer can be caused solely by protein imbalances within cells, a study of ovarian cancer has found. The discovery is a major breakthrough because, until now, genetic aberrations have been seen as the main cause of almost all cancer.
.....The research, led by scientists at the University of Leeds and The University of Texas MD Anderson Cancer Center, focused on the "Akt pathway," ( Protein kinase B (PKB), also known as Akt ) a signalling pathway within cells that drives cancer formation and the spread of cancers through the body......
ScienceDaily
Journal Reference:
- Z Timsah, Z Ahmed, C Ivan, J Berrout, M Gagea, Y Zhou, G N A Pena, Xin Hu, C Vallien, C V Kingsley, Y Lu, J F Hancock, J Liu, A B Gladden, G B Mills, G Lopez-Berestein, M-C Hung, A K Sood, M Bogdanov, J E Ladbury. Grb2 depletion under non-stimulated conditions inhibits PTEN, promotes Akt-induced tumor formation and contributes to poor prognosis in ovarian cancer. Oncogene, 2015; DOI: 10.1038/onc.2015.279
Too much, too late: Aggressive measures and the timing of end of life care discussions in women with gynecologic malignancies
abstract
Highlights
- •
- Reviews timing and location of end of life discussions with gyn-oncology patients
- •
- Evaluates compliance with National Quality Forum (NQF) metrics of care
- •
- A high rate of inpatient and late end of life discussions is noted in this cohort.
Objective
This
study describes the patterns of end of life (EOL) discussions and their
impact on the use of aggressive measures in women with terminal
gynecologic malignancies at a single institution.
Methods
An
IRB-approved retrospective chart review identified 136 patients who
died of gynecologic cancer between 2010 and 2012 with at least one
interaction with their oncologists in the last 6 months of life.
Aggressive measures were defined as chemotherapy within the last 14 days
of life, emergency department (ED) visits, hospital and intensive care
unit (ICU) admissions within the last 30 days of life, and inpatient
deaths. The frequency and timing of EOL conversations were recorded.
Utilization of hospice care was also described.
Results
In
the last 30 days of life, 54 (40%) patients were evaluated in the ED,
67 (49%) were admitted into hospital, and 16 (12%) were admitted to the
ICU. Thirteen patients (10%) had chemotherapy in the last 14 days of
life. Ninety-seven (71%) patients had a documented EOL conversation,
eighteen (19%) as outpatients, and 79 (81%) as inpatients. Thirty (22%)
patients died in the hospital. At the time of death, 55 (40%) patients
were enrolled in outpatient hospice care. The mean amount of time in
hospice was 28 days.
Conclusions
End
of life care discussions rarely occurred in the outpatient setting or
> 30 days before death. Inpatient encounters led to discussions about
hospice and code status. Evaluation in the ED frequently resulted in
escalation of care. Earlier EOL care discussions resulted in less
aggressive measures.
Do All BRCA Mutations Come with the Same Cancer Risk?
Insight
Women born with mutations in the genes BRCA1 or BRCA2 have an increased risk of developing breast and ovarian cancer, but the degree of increase depends on a variety of factors.
....Investigators at Dana-Farber are tracking the links between environment, heredity, and cancer in a study known as Project SEARCH.....
Cancer symptom awareness and barriers to symptomatic presentation in England[mdash]are we clear on cancer[quest]
open access
.... Women were significantly more likely than men to both recognise common cancer symptoms and to report barriers. Women were much more likely compared with men to report that fear would put them off from going to the doctor......Women were more likely than men to recognise each cancer symptom, except ‘persistent unexplained pain’.....
..... Finally, understanding the reasons why people in our sample identified certain barriers, for example, why people worry about wasting the doctor’s time, could further improve the effectiveness of future campaigns. Our findings could contribute to improving cancer survival in England to match the best in Europe by helping to develop targeted campaigns promoting early presentation of cancer symptoms.
BRCA1 and BRCA2 mutations sensitize to chemotherapy in patient-derived pancreatic cancer xenografts
open access
.... Clinical data in ovarian cancer show that patients with
BRCA1 and BRCA2 mutations show higher response rates to treatment with
cisplatin and other DNA-damaging agents resulting in improved outcome (Dann et al, 2012; Muggia and Safra, 2014).
Similar observations have been made in case reports of patients with
pancreatic cancer, suggesting that BRCA1 and BRCA2 mutations may
sensitise to treatment with platinum drugs (Lowery et al, 2011; Sonnenblick et al, 2011). This is supported by preclinical studies using established pancreatic cancer cell lines (van der Heijden et al, 2005),
and also by a large retrospective analysis of 71 pancreatic cancer
patients with germline BRCA1 and BRCA2 mutations, where it was reported
that patients with stage 3/4 disease who were
treated with a platinum-containing regimen had a median survival of 22
months, compared with 9 months for those who did not receive platinum (Golan et al, 2014).
There
are important unanswered questions concerning the optimum design of
platinum-containing treatment protocols for this group of patients, as
well as the role of newer agents such as inhibitors of poly-ADP-ribose
polymerase (PARP) that have shown early promise in other cancer patients
carrying germline BRCA mutations......Discussion
- Background:
- Methods:
- Results:
- Discussion:
- Materials and methods
- Results
- Discussion
- Conflict of interest
- References
- Acknowledgements
- Figures and Tables
Tumour response, correlates of survival and clinical benefit
Nature Reviews Clinical Oncology
We are all familiar with the metrics of tumour shrinkage and time to the development of disease progression as important end points in clinical trials. This tenet is based on findings of numerous studies over several decades that have demonstrated a link between agents that cause tumour shrinkage in a cancer population and its correlation with an overall survival improvement. The problem is that the inevitable variation in how these definitions and criteria have been applied over many decades in clinical trials has led to different conclusions about the efficacy of a treatment. Added to this complexity are the following issues: non-measurable lesions, differences obtained with the method of assessment of progression (imaging versus clinical examination), changes in non-target lesions versus target lesions, impact of lesions that coalesce or split on treatment, to name but a few. When considering the additional complexities posed by these factors, it is perhaps not surprising that tumour response is often a poor indicator of survival outcome. Yet, how can this be reconciled to allow the field of oncology to move forward............
AllTrials US campaign officially launched
announcement
29th July 2015
We are delighted to announce that today AllTrials USA has officially launched. Today 50 patient support groups, medical societies, universities and consumer groups are coming together to launch the AllTrials campaign in the US and to say:
“We are calling on everyone in
our sector to join us in supporting the AllTrials campaign. Hundreds of
thousands of patients have taken part in clinical trials which have
never reported results. For every day that passes, more information is
at risk of being lost forever. We have to make every clinical trial
count. Join us today.”
AllTrials – AllTrials US campaign officially launched
announcement
29th July 2015
We are delighted to announce that today AllTrials USA has officially launched. Today 50 patient support groups, medical societies, universities and consumer groups are coming together to launch the AllTrials campaign in the US and to say:
“We are calling on everyone in
our sector to join us in supporting the AllTrials campaign. Hundreds of
thousands of patients have taken part in clinical trials which have
never reported results. For every day that passes, more information is
at risk of being lost forever. We have to make every clinical trial
count. Join us today.”
ecancer - Cancer and metabolism (special issue)
ecancer
Cancer and metabolism
Guest Editor: Luca MazzarellaThis special issue centres around the field of metabolism, which has become one of the hot topics of the moment, especially as applied to cancer.....
Special Issue articles
Why does obesity promote cancer?
open access
Special Issue
Why does obesity promote cancer? Epidemiology, biology, and open questions
Keywords: obesity, body mass index, insulin, inflammation, DNA damage
Abstract
The association between obesity and/or metabolic syndrome and an
elevated mortality from cancer has been confirmed by an astonishing
number of studies across nations and ethnicities, such that obesity is
now recognised to be among the most prominent cancer risk factors
worldwide.
Despite this overwhelming evidence and the societal impact of obesity,
we know surprisingly little about the underlying molecular mechanisms.
This knowledge gap is a major obstacle to the implementation of
effective lifestyle change policies. As the scientific community is
insecure on what messages it should deliver, administrators are
uncertain as to what exactly to recommend, and consumers are confused
about whom to believe. This leaves the field flooded with
pseudo-scientific recommendations that are hard to eradicate.....
Gynaecological cancers (note: nothing on ovarian cancer)
Conclusion
The discourse on obesity and cancer has become dominant in public
debate. Some aspects of this issue are clearly established beyond any
reasonable doubt, namely the impact of obesity prior to diagnosis on
specific cancer risks and on survivor outcome. Other aspects, such as
the exact molecular mechanisms and the extent to which lifestyle changes
can modify risk, still await definitive proof. Ultimately, the debate
revolves on how much we can modify our cancer risk by intervening on the
most basic of animal activities: nutrition. Some might find it tempting
to dismiss this debate on the grounds that cancer risk (especially for
those cancers where a single environmental factor cannot be identified)
is mostly determined by ‘bad luck’, an un-escapable randomness in our
stem cells’ DNA mutation accumulation rate [52].
It is clearly not so, but it is also true that our understanding of how
nutrition impacts on cancer is far from complete. This creates fertile
ground for the proliferation of pseudo-scientific recommendations and
bogus ‘super healthy’ nutritional supplements. Likely, some mechanisms
and specific lifestyle interventions may have stronger impact on
specific cancers. It is also likely that an individual’s genetic makeup
may influence response to diet, as we find variable genetic
predisposition to specific cancers and genetically determined
differences in metabolism. In the wave of medicine personalisation, it
is not hard to imagine a future in which lifestyle plans will be
tailored to individual risk profile and metabolism.
Pharmacological treatments for fatigue associated with palliative care
Cochrane: Featured Review (update)
Objectives
Authors' conclusions
Based on limited evidence, we cannot recommend a specific drug for the treatment of fatigue in palliative care patients. Fatigue research in palliative care seems to focus on modafinil and methylphenidate, which may be beneficial for the treatment of fatigue associated with palliative care although further research about their efficacy is needed. Dexamethasone, methylprednisolone, acetylsalicylic acid, armodafinil, amantadine and L-carnitine should be further examined. Consensus is needed regarding fatigue outcome parameters for clinical trials.
Tuesday, July 28, 2015
Screening for pancreatic cancer in familial high-risk individuals: A systematic review
HRI = High Risk Individuals
open access
..... We chose familial HRIs as research subjects. In this population, there are also individuals with high risks for other diseases. Peutz-Jeghers syndrome with STK11/LKB1 gene mutation[36], hereditary pancreatitis with PRSS1 gene[37,38] or SPINK1 gene mutation[39], familial atypical multiple mole melanoma syndrome with CDKN2A or p16 gene mutations[40], hereditary breast ovarian cancer syndrome with BRCA2 and BRCA1 gene mutations[41,42], and Lynch syndrome with mismatch repair genes[43] are found in high risk populations, who should also receive attention. Nevertheless, these are not completely independent. Familial HRIs may also have gene mutations. The PRSS1 gene mutation is the main influencing factor in hereditary pancreatitis, an autosomal dominant disease. BRCA2 is one of the most common mutations, and was as high as 17% in one study[44]. Future studies on HRIs with gene mutations should be carried out to determine if they have a higher risk than HRIs without gene mutations. In addition, because of the complex nature of the pedigrees in pancreatic cancer, Wang et al[45] designed a tool known as PancPRO to identify familial HRIs, which was used for selecting and screening......
Peer-review
This
is a good systematic review in which the authors analyzed the benefits
and harms of pancreatic cancer screening in familial high-risk
individuals. The results are interesting, and suggest that pancreatic
cancer screening in familial HRIs can improve detection rate and prolong
lifetime. In addition, it can influence psychological functions and
increase the economic burden.
selected references (all references see article above)
36. (open access - pdf file link)
Giardiello
FM, Brensinger JD, Tersmette AC, Goodman SN, Petersen GM, Booker SV,
Cruz-Correa M, Offerhaus JA. Very high risk of cancer in familial
Peutz-Jeghers syndrome. Gastroenterology. 2000;119:1447-1453.[PubMed]
41. (open access)
Thompson D, Easton DF. Cancer Incidence in BRCA1 mutation carriers. J Natl Cancer Inst. 2002;94:1358-1365.[PubMed]
42. (open access)
van
Asperen CJ, Brohet RM, Meijers-Heijboer EJ, Hoogerbrugge N, Verhoef S,
Vasen HF, Ausems MG, Menko FH, Gomez Garcia EB, Klijn JG. Cancer risks
in BRCA2 families: estimates for sites other than breast and ovary. J Med Genet. 2005;42:711-719.[PubMed] [DOI]
43. (open access)
Kastrinos
F, Mukherjee B, Tayob N, Wang F, Sparr J, Raymond VM, Bandipalliam P,
Stoffel EM, Gruber SB, Syngal S. Risk of pancreatic cancer in families
with Lynch syndrome. JAMA. 2009;302:1790-1795.[PubMed] [DOI]
Vitamin D and Cancer: Diversity, Complexity, and Still a Ways to Go
abstract
Vitamin D has taken a center-stage role in our basic and population research quest for the panacea for all human maladies, including cancer, yet sufficient evidence for a beneficial role has existed only for bone health. This Commentary discusses and places into a broader context the report of Chandler and colleagues that found a protective association for higher vitamin D status in colorectal cancer in women, consistent with most other cohort studies but not with limited supplementation trial data. Little human evidence exists for the preventive potential in other malignancies, including breast cancer, with the exception of possible benefit in bladder cancer and an adverse serologic association with prostate cancer (pancreatic cancer risk may be similarly influenced) that is supported by vitamin D genetic data. Current vitamin D trials are examining high-dose supplementation (i.e., 1,600–3,333 IU daily) for effects on multiple outcomes, but they may not have sufficient power to test efficacy in colorectal or other specific malignancies and are unlikely to inform any benefit for higher physiologic levels. A more complete understanding of vitamin D and human carcinogenesis will come from multifaceted lines of research, including elucidation of organ site–specific biologic mechanisms, prospective serologic analyses, testing of vitamin D–related genetic variation, and short-term clinical–metabolic biomarker studies of multidose vitamin D supplementation, including metabolomic profiling of controlled supplementation in these and past or ongoing trials. Cancer Prev Res; 8(8); 1–5. ©2015 AACR.
See related article by Chandler et al., p. 675
Initial assessment of patient handoff in accredited general surgery residency programs in the U.S. & Canada
Can J Surg, Vol. 58, No. 4, August 2015
....our study was restricted to junior surgical residents and did not include senior
level residents, which may overstate the lack the training and/or inexperience with handoffs.....
open access: Initial assessment of patient handoff in accredited
general surgery residency programs in the United States and Canada: a cross-sectional survey
.....Of the American residents, 67% and 6% reported receiving an incomplete handoff that resulted in minor and major patient harm, respectively. These results mirrored those from Canadian reidents (63% minor and 7% major harm). The most frequent factor reported to improve the patient handoff process was standardization of the verbal handoff.....
Conclusion:
Our survey results indicate that the current patient handoff system con
tributes to patient harm. More efforts are needed to establish standardized forms of
verbal and written handoff to ensure patient safety and continuity of c
1 in 3 Patients With Cancer Meets the Criteria for Mental Disorders: What Does That Mean?
Blogger's Note: gynecologic cancers were grouped together in the original study
Correspondence (open access)
Author's Response (open access) (to Correspondence above)
open access: link to original article
Four-Week Prevalence of Mental Disorders in Patients With Cancer Across Major Tumor Entities
Four challenges we have to crack before immune therapy can revolutionize how we fight cancer
The Conversation (blog)
Author
PhD Candidate, Biological Design, School of Biological and Health Systems Engineering at Arizona State University
For a training immunologist like myself, immune therapies have opened new doors to understanding and treating cancers. In the future, immunotherapy could mean a personalized treatment, entirely tailored to an individual. As exciting as that sounds, we still have plenty of work to do, as there remains a lot we don’t know about the immune system. Here are some of the challenges we need to overcome to create these personalized treatments......
FDA Alert: Gadolinium-based Contrast Agents for MRI: Drug Safety Communication - FDA Evaluating
FDA Alert
July 27, 2015
Audience: Radiology
ISSUE: FDA is investigating the risk of brain deposits following repeated use of gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI). Recent publications in the medical literature have reported that deposits of GBCAs remain in the brains of some patients who undergo four or more contrast MRI scans, long after the last administration. It is unknown whether these gadolinium deposits are harmful or can lead to adverse health effects.
FDA, including its National Center for Toxicological Research (NCTR), will study this possible safety risk further. FDA is working with the research community and industry to understand the mechanism of gadolinium retention and to determine if there are any potential adverse health effects. Based on the need for additional information, at this time, FDA is not requiring manufacturers to make changes to the labels of GBCA products.
Monday, July 27, 2015
Pragmatic Randomized Trials Without Standard Informed Consent?
Abstract
Pragmatic Randomized Trials Without Standard Informed Consent?: A National SurveyPragmatic Randomized Trials Without Standard Informed Consent? | Annals of Internal Medicine
Background: Significant debate surrounds the issue of whether written consent is necessary for pragmatic randomized, controlled trials (RCTs) with low risk.
Objective: To assess the U.S. public's views on alternatives to written consent for low-risk pragmatic RCTs.
Design: National experimental survey (2 × 2 factorial design) examining support for written consent versus general notification or verbal consent in 2 research scenarios.
Setting: Web-based survey conducted in December 2014.
Participants: 2130 U.S. adults sampled from a nationally representative, probability-based online panel (response rate, 64.0%).
Measurements: Respondent's recommendation to an ethics review board and personal preference as a potential participant for how to obtain consent or notification in the 2 research scenarios.
Results: A majority of respondents in each of the 4 groups (range, 60.3% to 71.5%) recommended written informed consent, and personal preferences were generally in line with that advice. Most (78.9%) believed that the pragmatic RCTs did not pose additional risks, but 62.5% of these respondents would still recommend written consent. In contrast, a substantial minority in all groups (28.5% to 39.7%) recommended the alternative option (general notification or verbal consent) over written consent.
Limitation: Framing effects could have impacted respondents' attitudes, and nonrespondents may have differed in levels of trust toward research or health care institutions.
Conclusion: A majority of the public favored written informed consent over the most widely advocated alternatives for low-risk pragmatic RCTs; however, a substantial minority favored general notification or verbal consent.
Ovarian vein thrombosis after debulking surgery for ovarian cancer: epidemiology and clinical significance
abstract
Objective
Ovarian
vein thrombosis is associated with pregnancy and pelvic surgery.
Postpartum ovarian vein thrombosis is associated with infection and a
high morbidity rate and is treated with anticoagulant and intravenous
antibiotic therapy. The natural history of such thrombotic events after
debulking surgery for ovarian cancer has not been well described. Our
objective was to characterize the presentation and outcomes for patients
with this condition at our institution.
Study Design
We
conducted a retrospective study of patients who underwent surgical
debulking for ovarian cancer at Memorial Sloan Kettering Cancer Center
between the years 2001 and 2010. Patients were included if contrast
computed tomography scans of both the abdomen and pelvis were performed
within 12 weeks before and 12 weeks after the surgery. The images were
reviewed to assess for the presence and extent of a new postoperative
ovarian vein thrombosis. When available, subsequent studies were
assessed for thrombus progression. Medical records were reviewed to
determine whether anticoagulation was used for treatment of the
thrombotic episode and to record the occurrence of any new significant
venous thromboembolic event in the next year.
Results
One
hundred fifty-nine patients had satisfactory imaging. New ovarian vein
thrombosis was a common complication of debulking surgery, as found in
41 of patients (25.8%). Only 5 women with ovarian vein thrombosis were
started on anticoagulation, of which 2 individuals had an independent
venous thromboembolic event as indication for treatment. Only 2 of the
ovarian vein thromboses (4.9%) progressed to the inferior vena cava or
left renal vein on subsequent scan. The estimated cumulative incidence
of venous thromboembolism 1 year after the first postoperative scan was
17.1% for patients in the new ovarian vein thrombosis group vs 15.3% of
individuals for the group without a postoperative ovarian vein
thrombosis (P = .78).
Conclusion
Ovarian
vein thrombosis is commonly encountered after debulking surgery for
ovarian cancer. Anticoagulation is usually not indicated, and clinically
meaningful thrombus progression rarely occurs.
Identifying novel hypoxia-associated markers of chemoresistance in ovarian cancer
open access
Conclusions
Overall, these results show that the most important determining factor for development
of resistance is the presence of hypoxia during the treatment period, not prior to
treatment thus highlighting the potential importance of simultaneously reducing tumour
hypoxia and treating with chemotherapy. This may have particular importance in patients
with large tumours who receive neoadjuvant chemotherapy. A number of pathways are
responsible for the resistance to cisplatin observed due to hypoxia, and that there
are many candidate biomarkers of hypoxia which could be explored in the context of
ovarian cancer. We have also provided an initial validation of selected hypoxia-associated
biomarkers in ovarian tumour samples. It will be important to expand the study and
to validate these results at the protein level in future studies in order to elucidate
their true importance.
Sunday, July 26, 2015
The role of diagnostic ureteroscopy in the era of computed tomography urography
Blogger's Note: of interest to Lynch Syndrome patients
open access
Background
Upper urinary tract urothelial carcinoma (UTUC) is an uncommon malignancy, accounting for ~5 % of urothelial tumors [1]. The diagnosis of UTUC can be challenging, requiring a combination of radiographic, cytologic and endoscopic means. Time honored radiological tools such as intravenous urography and retrograde uretropyelograpy are currently replaced by modern computerized tomography urography (CTU) [2]. Diagnostic ureteroscopy is often performed following CTU. Flexible ureteroscopy allows exploration of the upper urinary tract and is beneficial when diagnostic uncertainty exists. It has the advantages of offering direct view of the tumor, ruling out other pathologies and achieving tissue diagnosis. Although nephrouereterectomy is considered the gold standard treatment of UTUC, endoscopic ablation and resection of the tumor can be successfully utilized in selected cases based on tumor size and histology, as determined during ureteroscopoy.......Late Breaking Abstracts deadline notice: ECCO/ESMO 2015
Late Breaking Abstracts Deadine Dates
The European Cancer Congress 2015
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Abstract submission open: 22 July 2015
Abstract submission deadline: 5 August 2015, 21:00 Central European time
Tea consumption and the incidence of cancer: a systematic review
abstract
The aim of this study was to summarize the current evidence on the strength of associations between tea consumption and the incidence of cancer at different sites. We searched PubMed, Embase and the Cochrane Library for relevant articles published before October 2013. Prospective studies that reported effect estimates of cancer incidence, with 95% confidence intervals (CIs), for more than two categories of tea consumption were included. We analysed 87 datasets (57 articles), which included a total of 49 812 incident cases. Overall, high tea consumption had no significant effect on the risk of gastric, rectal, colon, lung, pancreatic, liver, breast, prostate, ovarian, bladder cancers or gliomas. However, high tea consumption was associated with a reduced risk of oral cancer (risk ratio 0.72; 95% CI 0.54–0.95; P=0.021). A dose–response meta-analysis suggested that an increase in tea consumption by one cup per day was associated with a reduced risk of oral cancer (risk ratio 0.89; 95% CI 0.80–0.98; P=0.022), but had little effect on the incidence of other cancers. Subgroup analysis indicated that an increase in the consumption of black tea by one cup per day was associated with an increased risk of breast cancer. Moreover, in western countries, we found that an increase in the consumption of tea by one cup per day was associated with a reduced risk of bladder cancer. Increased tea consumption has no significant effect on the risk of common malignancies. For some cancer types, associations differ according to sex, ethnicity and tea type.
Saturday, July 25, 2015
An overview of early investigational therapies for chemoresistant ovarian cancer
Abstract
INTRODUCTION:
Epithelial
ovarian cancer (EOC) is the fourth commonest cause of female cancer
death in the developed world. Although progress in treatment has
improved survival, ∼ 80% of patients with advanced EOC will experience a
recurrence and eventually will become resistant to chemotherapy. The
aim of treatment for chemoresistant EOC has traditionally been limited
to palliation of symptoms but the recent introduction of new therapies
targeting molecular pathways is beginning to demonstrate improvements in
disease control.
Areas covered:
This review provides an overview of early investigational drugs for the treatment of 'platinum-resistant' EOC. The article is based on English peer-reviewed articles located on MEDLINE and related abstracts presented at major international meetings.
Expert opinion:
Drugs targeting several pathways are increasingly used to treat 'platinum-resistant' EOC. Currently, drugs targeting the angiogenesis pathway have been shown to significantly improve patient outcome. Studies are also being undertaken with inhibitors of poly(ADP-ribose) polymerase (PARP), targeting the DNA repair pathway as it is possible that the benefits seen with these agents in 'platinum-sensitive' disease will apply to those with 'platinum-resistant' disease. The discovery of predictive biomarkers that identify patients which benefit from these targeted therapies is paramount to the success of these treatments in the future.
Areas covered:
This review provides an overview of early investigational drugs for the treatment of 'platinum-resistant' EOC. The article is based on English peer-reviewed articles located on MEDLINE and related abstracts presented at major international meetings.
Expert opinion:
Drugs targeting several pathways are increasingly used to treat 'platinum-resistant' EOC. Currently, drugs targeting the angiogenesis pathway have been shown to significantly improve patient outcome. Studies are also being undertaken with inhibitors of poly(ADP-ribose) polymerase (PARP), targeting the DNA repair pathway as it is possible that the benefits seen with these agents in 'platinum-sensitive' disease will apply to those with 'platinum-resistant' disease. The discovery of predictive biomarkers that identify patients which benefit from these targeted therapies is paramount to the success of these treatments in the future.
LIFE AND DEATH CAN BE STRONG MOTIVATION media (ovarian cancer....)
media
Rule No. 218 is “Grand passion will take you further than good grades,” and nothing focuses a passion more than when a problem is directly connected to your own life, as in living or dying.
Meet Laura Shawver. At the age of 49 in 2006, she was diagnosed with clear cell ovarian cancer. After getting the diagnosis, she was first surprised, then shocked and finally angry to learn that doctors had no idea what treatment to recommend for her particular case. This disease did not know who it was dealing with. Shawver was not your typical patient.
First, she has a Ph.D. in pharmacology, and second, she is relentless. She knew that a molecular profile of her tumor would help in determining the options, and she was upset that she could not easily get this done for ovarian cancer, even though it was being done regularly for patients with breast, lung and colon cancers......
Friday, July 24, 2015
Sweet and Vicious: Sugar and Sugar Substitutes
CureToday article
Sugar
does not feed cancer cells any differently than it feeds healthy cells.
- See more at:
http://www.curetoday.com/community/amanda-bontempo/2015/07/sweet-and-vicious-sugar-and-sugar-substitutes?utm_source=Informz&utm_medium=Cure+Today&utm_campaign=CURExtra%2Demail%2DIncyte%2DJakafi%2D7%2D24%2D15#sthash.0JDxNJwB.dpuf
Sugar
does not feed cancer cells any differently than it feeds healthy cells.
- See more at:
http://www.curetoday.com/community/amanda-bontempo/2015/07/sweet-and-vicious-sugar-and-sugar-substitutes?utm_source=Informz&utm_medium=Cure+Today&utm_campaign=CURExtra%2Demail%2DIncyte%2DJakafi%2D7%2D24%2D15#sthash.0JDxNJwB.dpuf
Sugar does not feed cancer cells any differently than it feeds healthy cells......Thesis: Drugs with potential chemopreventive properties in relation to epithelial ovarian cancer
pdf file Danish Medical Journal
Drugs with potential chemopreventive properties in relation to epithelial ovarian cancer –a nationwide case-control study (note: includes section on statins)
......The results of this PhD thesis add important knowledge to the
area of chemoprevention in relation to epithelial ovarian cancer......
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