abstract Unclassifiable Malignant Extraovarian Sex Cord-Stromal Tumors:
Report of 3 Cases and Review of Extraovarian Sex Cord-Stromal Tumors.
We report 3 cases of primary extraovarian unclassifiable
malignant sex cord-stromal tumors. In all cases, the tumors involved the
pelvis, peritoneum, and/or omentum and the morphologic features were
essentially those of a poorly differentiated malignant neoplasm. A
diagnosis of sex cord-stromal tumor was made on the basis of expression
of several markers of ovarian sex cord-stromal tumors and exclusion of
other neoplasms. In 1 case, an elevated serum testosterone was present
at tumor progression. In reporting these cases, we draw attention to the
problems in establishing a diagnosis that can be attributed to the
extreme rarity of sex cord-stromal tumors in an extraovarian location
and the rarity of unclassifiable malignant sex cord-stromal tumors in
general, resulting in pathologists not considering this diagnosis. We
review sex cord-stromal tumors occurring in an extraovarian location.
Expanded genetic testing of BRCA mutations has led to identification of
more reproductive-aged women who test positive for the mutation which
might impact attitudes and decisions about relationships, childbearing
and the use of preimplantation genetic diagnosis (PGD) and prenatal
diagnosis (PND). A cross-sectional survey was administered to 1081
self-reported BRCA carriers to investigate how knowledge of BRCA status
influences these issues. The mean age at BRCA test disclosure was
44 years and 36 % reported a personal history of cancer. Of 163 women
who were unpartnered, 21.5 % felt more pressure to get married. Of 284
women whose families were not complete, 41 % reported that carrier
status impacted their decision to have biological children. Women with a
history of cancer were more likely to report that knowledge of BRCA+
status impacted their decision to have a child (OR 1.8).
Fifty-nine percent thought PGD should be offered to mutation carriers
and 55.5 % thought PND should be offered. In conclusion, knowledge of
BRCA status impacts attitudes regarding relationships and childbearing,
and most carriers believe that PGD and PND should be offered to other
carriers. This study suggests that BRCA carriers desire and would
benefit from reproductive counseling after test disclosure.
In a massive cleanup, Springer and BioMed Central announced today
they are retracting 58 papers for several reasons, including
manipulation of the peer-review process and inappropriately allocating
authorship.
The papers appeared in seven journals, and more are under investigation.
In a release issued today, the publishers note:
After receiving allegations of plagiarism confined to two
journals, we immediately commenced an extensive investigation across
our entire portfolio. In doing so, two teams dedicated to investigating
issues around research integrity, the Research Integrity Group at BioMed
Central and the Springer Ethics Team, identified a group of papers
across seven journals that raised concerns relating to a variety of
issues.
BioMed Central has identified 28 articles that will be retracted and
is investigating 40 more articles. Springer has identified 30 articles
that will be retracted, with a further 9 articles that need further
investigation.....
Click here for a full list of papers. The most affected journals are Tumor Biology (25 papers) and Diagnostic Pathology (23 papers). The other journals are Comparative Clinical Pathology (one paper), Journal of Parasitic Diseases (four papers), Cancer Cell International (two papers), Journal of Ovarian Research(two papers), and World Journal of Surgical Oncology (one paper).
This is not the first time the journals have done a massive sweep to clean up the literature — in March, 2015, BMC pulled 43 papers for fake reviews; a few months later, in August, Springer did the same for 64 papers.
Cancer
pain is an important and distressing symptom that tends to increase in
frequency and intensity as the cancer advances. For people with advanced
cancer, the prevalence of pain can be as high as 90%. It has been
estimated that 30% to 50% of people with cancer categorise their pain as
moderate to severe, with between 75% and 90% of people with cancer
experiencing pain that they describe as having a major impact on their
daily life. Epidemiological studies suggest that approximately 15% of
people with cancer pain fail to experience acceptable pain relief with
conventional management. Uncontrolled pain can lead to physical and
psychological distress and can, consequently, have a drastic effect on
people's quality of life.
OBJECTIVES:
To
determine the analgesic efficacy of hydromorphone in relieving cancer
pain, as well as the incidence and severity of any adverse events.
SEARCH METHODS:
We
searched the Cochrane Central Register of Controlled Trials, MEDLINE,
Embase and clinical trials registers up to April 2016. There were no
language, document type or publication status limitations applied in the
search.
PARP is an enzyme that is involved in
repairing damaged DNA. PARP inhibitors may help keep cancer cells from
repairing their damaged DNA, causing them to die.
Credit: National Human Genome Research Institute
A team led by NCI researchers has identified a potential biomarker that could help predict whether a tumor will respond to a relatively new class of targeted cancer drugs known as PARP inhibitors. The team’s findingsExit Disclaimer, published September 27 in Oncotarget, showed that cancer cell lines with high expression levels of the gene SLFN11 were more sensitive than cells with low SLFN11 expression to the PARP inhibitors olaparib (Lynparza™) and talazoparib. Cancer cell lines in which the SLFN11 gene was inactivated were resistant to both drugs.
Olaparib is approved by the Food and Drug Administration for the
treatment of certain patients with advanced ovarian cancer whose tumors
have mutations in the BRCA1 or BRCA2 genes. Olaparib
and other PARP inhibitors are also in advanced clinical testing for
other cancers, including prostate, breast, and colon cancer.
The new study also provided evidence that another class of drugs
called ATR inhibitors, which are being studied for the treatment of
various cancers, may be able to overcome resistance to PARP inhibitors
caused by inactivation of SLFN11.
Links Between SLFN11 and Response to DNA-Damaging Drugs
Previous work by the NCI team, led by Yves Pommier, M.D., Ph.D., of NCI’s Center for Cancer Research, and by others, has shown that SLFN11 is inactivated in nearly half of all human cancer cell lines tested. SLFN11
expression also varies widely in tumor samples from patients with
ovarian, breast, lung, prostate, and colon cancer, as measured in
samples from The Cancer Genome Atlas, Dr. Pommier said.
PARP inhibitors block the actions of the PARP family of proteins,
which play an important role in repairing DNA damage in cells. Cancer
cells that cannot repair their damaged genetic material die.
Previous studies by Dr. Pommier’s lab, using data from the NCI-60 human tumor cell lines screen, revealed a previously unsuspected association between SLFN11 expression and responsiveness to a broad range of DNA-damaging cancer therapies, including topoisomerase inhibitors and cisplatin. Specifically, they observed that cells with high expression of SLFN11 are more sensitive to these drugs than cells with low expression.
To examine whether SLFN11 expression is also associated with
the response to PARP inhibitors, Dr. Pommier’s team studied several
human tumor cell lines with varying levels of SLFN11 expression. They found a correlation between higher SLFN11
expression and higher sensitivity to olaparib and talazoparib, two of
the most potent PARP inhibitors. In addition, tumor cells in which the SLFN11 gene was experimentally inactivated were also resistant to both drugs.
The team also showed that, in mouse models of small cell lung cancer, inactivation of SLFN11 was associated with resistance to combination therapy consisting of a PARP inhibitor and the chemotherapy drug temozolomide. A recent study by researchers at Memorial Sloan Kettering Cancer Center reported similar findings.
Tumors with mutations in the BRCA1 or BRCA2
genes—which are involved in repairing DNA damage in cells—are known to
be particularly sensitive to PARP inhibitors, Dr. Pommier said. But in
their study, he continued, “we found that regardless of whether the BRCA gene is switched off or on, if SLFN11 is off, the cancer is resistant to PARP inhibitors; if SLFN11 is on, the cancer will tend to be sensitive to PARP inhibitors.”
These findings, he said, suggest that, in addition to BRCA mutations, expression levels of SLFN11 can be considered as criteria for the use of PARP inhibitors.
Overcoming Resistance
Finally, Dr. Pommier’s team investigated whether a drug that blocks
the actions of a protein known as ATR could make tumors with inactivated
SLFN11 sensitive to PARP inhibitors. ATR plays a key role in
coordinating DNA repair and the progression of cells through the cell
cycle—the series of steps a cell goes through each time it divides. When
a cell’s DNA is damaged, ATR puts the cell cycle on hold, essentially
giving the cell time to repair the damage before it continues to divide.
For these experiments, the team used four human cancer cell lines in which they had experimentally deleted the SLFN11 gene. These experiments showed that treating cells lacking SLFN11 with ATR inhibitors could restore their sensitivity to olaparib and talazoparib.
“Clinicians who are designing clinical trials need to have
preclinical data to justify whether they should combine two drugs,” Dr.
Pommier said. “We provide evidence that even if SLFN11 is off
and a tumor is intrinsically resistant to a PARP inhibitor, you may be
able to convert it to a sensitive tumor by adding an ATR inhibitor.”
Potential Clinical Applications for Precision Medicine
The study’s lead author, Junko Murai, M.D., Ph.D., said she hopes to develop SLFN11 expression as a biomarker to predict which patients are most likely to respond to PARP inhibitors.
That will require additional studies to measure SLFN11 expression in patient tumor samples, rather than in cell lines or mouse models. So far, Dr. Pommier’s team has done retrospective studies looking at SLFN11 expression in tumor samples from patients treated with DNA-damaging drugs. In one studyExit Disclaimer,
for example, patients with ovarian cancer who had been treated with
cisplatin tended to have better outcomes if their tumors had high SLFN11 expression levels than if they had low levels. Another studyExit Disclaimer
showed a similar pattern in patients with Ewing sarcoma treated with a
topoisomerase inhibitor or with olaparib and temozolomide.
But more rigorous evidence from clinical trials is needed before SLFN11
expression can be used as a biomarker of responsiveness to PARP
inhibitors and other DNA-damaging agents, Dr. Pommier said. In a
clinical trial, researchers could test the levels of SLFN11
expression from tumor samples obtained immediately before patients begin
drug treatment and assess whether its expression is correlated with the
response to treatment.
Another important next step, the study authors said, will be to better understand the mechanism of action of SLFN11 in the response to PARP inhibitors.
Background: Surgery
followed by platinum-based chemotherapy is the standard of care for
MOGCTs, except for stage IA dysgerminoma and
stage IA grade 1 immature teratoma where
surveillance only is recommended. The role of adjuvant chemotherapy and
surgical
staging is debated.
Patients and Methods: Data from 144 patients with stage I MOGTs were collected among MITO centers (Multicenter Italian Trials in Ovarian Cancer)
and analysed.
Results: 55(38.2%)
patients were affected by dysgerminomas, 49(34%) by immature teratomas,
26(18.1%) by yolk sac tumors and 14(9.7%)
by mixed tumors. 73(50.7%) patients receive surgery
plus chemotherapy, while 71 (49.3%) patients underwent surgery alone.
The latter group included 32 dysgerminomas (14
IA-13 Ix, 3 IB, 2 IC), 34 immature teratomas (20 1A-13 IA grade 1, 6 Ix,
1
IB, 7 IC), 4 mixed tumors and 1 yolk sac tumor. 44
patients did not received chemotherapy, even if it would have been
indicated
by recommended approach. 94(65.3%) patients
received peritoneal surgical staging. 23(15.9%) developed a recurrence.
Incomplete
surgical staging was associated with recurrence
(p<0.05; OR 2.37) at Cox regression analysis. 7 patients died. 4
patients
were affected by yolk sac tumors, 2 by mixed tumors
and 1 by immature teratoma. 5 patients died for disease, 1 for acute
leukemia
and 1 for suicide. Prognostic parameters analyses
showed that yolk sac component is a predictor for survival (p<0.05) Five-years OS rates were 96.8% and 88.7% in surgically staged and incomplete staged group, while 93.8% and 94.1% in
standard treatment and in the surveillance group, respectively.
Conclusion: This study
shows that surveillance seems not to affect survival; chemotherapy
should be reserved for relapse resulting in
high cure rate. Incomplete peritoneal surgical
staging is associated with recurrence. Yolk sac histology worsens the
prognosis.
Researchers of the Wihuri Research Institute and the University of
Helsinki, Finland, have found that some of the harmful effects of a
commonly used cancer drug can be alleviated by using gene therapy that stimulates blood vessel growth in the heart.
Doxorubicin treatment, which is commonly used in a variety of cancers,
leads to cardiac atrophy and body wasting. They found that in mouse
heart, doxorubicin leads to blood vessel rarefaction, which was
prevented by treatment with gene therapy using the VEGF-B growth factor.
As advances in cancer treatment have decreased deaths from cancer,
doxorubicin-induced heart problems have become an increasing problem.
The new findings give hope that in future the heart could be protected
by gene therapy, allowing more thorough cytostatic cancer treatment.
Thus, the cancer itself would be treated more effectively and the
adverse effects could be avoided, explains Markus Räsänen, MD, who made
the discovery during his thesis studies.
"Doxorubicin, a cytostatic agent of the anthracycline class, that was
used in this study has been a target of intensive research in the
scientific world for a long time, and its role has been described in
thousands of research articles. This research article is the first one,
where blood vessel-directed therapy has a clear protective effect
against the doxorubicin toxicity", says Dr. Riikka Kivelä, who
supervised the study......
Expanded access, or “compassionate use,” allows patients and their
physicians to request from pharmaceutical medical products (drugs,
devices, biologics) that have not yet been approved by the U.S. Food and
Drug Administration (FDA). There are several steps you and your doctor
must take to get access to an unapproved medication, according to the
FDA’s Expanded Access Program.....
NCCN POLICY SUMMIT DATE >Friday, December 9, 2016 > REGISTER NOW! NCCN POLICY SUMMIT LOCATION > The National Press Club • Washington, DC
Early Bird Registration Fee Discounts Expire on November 4, 2016!
OVERVIEW
The National Comprehensive Cancer Network® NCCN®) invites you to attend the Value Tools for Patients in Cancer Care. The Summit will be held on Friday, December 9, 2016 at The National Press Club in Washington, D.C. from 7:30 AM– 3:00 PM.
Open Access: The transfer of multigene panel testing for hereditary breast and ovarian cancer to healthcare: What are the implications for the management of patients and families?
Until recently, the molecular diagnosis of hereditary breast and ovarian cancer (HBOC) was mostly based on BRCA1/2
testing. Next generation sequencing and the recent discovery of new
genes involved in HBOC now permit the transfer of genomic capture
targeting multiple candidate genes from research to clinical use.
However, the implications for the management of patients and their
families have not been extensively studied, in particular since some of
these genes are not well-established cancer predisposing genes.....
Mutations in other highly penetrant genes, such as PTEN, CDH1, STK11 and TP53, can cause cancer susceptibility syndromes [9-12], but remain rare. MLH1, MSH2, MSH6 and PMS2
also contribute to a hereditary risk of OC. The criteria for genetic
testing are specific to these predispositions, according to their
disease spectrum.
To
assess the prevalence of malnutrition in gynecologic cancer patients
using the Scored Patient- Generated Subjective Global Assessment
(PG-SGA) questionnaire.
MATERIALS AND METHODS:
A
total of 97 gynecologic cancer patients who never had any treatment but
were planned for surgery were enrolled. The patients were asked to
complete the scored PG-SGA form before the treatment was started.
Attending physicians were also asked to complete other information in
the PG-SGA form. Total scores were calculated and the patients were
classified into 3 nutritional status levels.
RESULTS:
Mean
age was 54 years. Postoperative diagnoses were endometrial cancer in 42
cases (43.2%), ovarian cancer in 29 cases (29.9%), and cervical cancer
in 26 cases (26.8%). Mean PG-SGA score was 5.2+4.7. Malnutrition (PG-SGA
B and C) was found in 52 patients (53.6%, 95% CI 43.7% - 63.2%).
Preoperative BMI, hemoglobin, serum albumin, and cancer stage were not
significantly associated with nutritional status. Malnutrition was
significantly more common among patients diagnosed with ovarian cancer,
compared to other types of cancer (79.3% vs. 42.6%, p 0.004).
CONCLUSIONS:
Prevalence
of malnutrition among gynecologic cancer patients was 53.5%, according
to the scored PG-SGA. Malnutrition was significantly more common among
patients with ovarian cancer.
abstract Experience with trabectedin + pegylated liposomal doxorubicin for recurrent platinum-sensitive ovarian cancer unsuited to platinum rechallenge
INTRODUCTION:
As
most patients with ovarian cancer experience multiple remissions and
relapses, oncologists must prepare ahead for long-term treatment. While
platinum-based regimens are standard of care for platinum-sensitive
recurrence, there are circumstances in which platinum rechallenge is not
the best approach. These situations include patients with limited
sensitivity to platinum; patients with residual toxicity from previous
platinum therapy; and patients at risk of developing hypersensitivity
reactions. An alternative regimen for these patients is the non-platinum
combination of trabectedin + pegylated liposomal doxorubicin (PLD).
Areas covered: In this review, case studies are presented to illustrate
how careful strategic planning, in terms of therapeutic choices and
optimal sequencing, can achieve good outcomes in difficult-to-treat
patients.
Expert commentary: Advantages with use of trabectedin + PLD in
selected patients with platinum-sensitive recurrent ovarian cancer
include additional time to recover from platinum-related toxicities,
avoidance of hypersensitivity reactions, and the 'sequence effect' by
which trabectedin may enhance response to next platinum and prolong
survival.
‘…the
limitation of relying solely on treatment-free interval cut-off points
for therapy selection [in recurrent ovarian cancer] is nowadays regarded
as a shortcoming’.
As
the course of ovarian cancer is typically characterized by multiple
remissions and relapses, careful strategic planning is required to
optimize management. Therapeutic decisions taken at any given stage can
impact on the efficacy and safety of future therapies. Newer cytotoxic
regimens and targeted therapies such as antiangiogenesis agents and poly
ADP ribose polymerase (PARP) inhibitors have led to improved outcomes
for patients with recurrent ovarian cancer. However, a consequence of
greater choice is the increased complexity of defining tailored
therapeutic approaches, including optimal timing of administration and
drug-sequencing strategies.
One
of the main indicators of prognosis and probability of response to
second- and subsequent-line therapy in recurrent ovarian cancer is the
progression-free interval after the last dose of the preceding line of
chemotherapy. Historically, patients have been classified as
platinum-refractory (≤4 weeks before disease progression),
platinum-resistant (<6 months), partially platinum-sensitive
(6–12 months), and platinum-sensitive (>12 months) with respect to
the interval between their last platinum application and a diagnosis of
relapse [1Ledermann JA, Raja FA, Fotopoulou C, et al. Newly
diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical
Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(Suppl 6):vi24–32.[CrossRef], [PubMed], [Web of Science ®]].
The standard-of-care paradigm has been to treat platinum-resistant
disease with non-platinum monotherapy and to treat platinum-sensitive
disease with platinum combinations. However, this treatment paradigm has
since been challenged and the limitation of relying solely on
treatment-free interval cut-off points for therapy selection is nowadays
regarded as a shortcoming. Although so-called platinum sensitivity may
partially predict chemotherapy sensitivity, newer therapies do not
necessarily follow this pattern; both antiangiogenesis agents and PARP
inhibitors may act independently of the platinum-free interval.
Furthermore, there are several profiles of so-called platinum-sensitive
patients for whom platinum rechallenge is not the best approach. These
include patients with a non-extensive platinum-free interval and
patients not suited to receive platinum due to residual toxicities,
hypersensitivity to platinum, or other reasons. For these patients,
trabectedin + pegylated liposomal doxorubicin (PLD) can be regarded as a
suitable non-platinum alternative [1Ledermann JA, Raja FA, Fotopoulou C, et al. Newly
diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical
Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(Suppl 6):vi24–32.[CrossRef], [PubMed], [Web of Science ®]].
Another potential positive impact of this strategy relates to the
hypothesis that intercalation of trabectedin + PLD before platinum
rechallenge may enhance the response to subsequent platinum by
resensitizing tumor cells to platinum.
For
many decades, a main objective in treating recurrent ovarian cancer has
been to increase life expectancy while minimizing the toxic effects of
chemotherapy. Modern treatment strategies offer potential to improve
overall survival, a stubbornly elusive therapeutic goal until recently.
In addition to environmental risk factors, hereditary genetic
alterations may also be involved in the tumorigenesis of UTUC.
Approximately 10–20% of all UTUCs have a hereditary background. It is
well established that the incidence of UTUC is 8–25 fold higher in Lynch
syndrome (also known as hereditary non-polyposis colorectal carcinoma;
HNPCC) (23,24).
The hMLH1 and hMSH2 are the most commonly damaged genes in Lynch
syndrome. If both alleles of one of these genes are affected by
mutation, deletion or epigenetic silencing, the mismatch-repair (MMR)
function is blocked resulting in the accumulation of damaged genes
ultimately leading to cancer formation with colorectal (type I) and
sometimes also extra-colonic location such as ovary or upper urinary
tract (type II) (24). For urothelial cancers of hereditary origin, the hMSH2 mutations are more prevalent as those of hMLH1 (25).
To classify UTUC into hereditary and sporadic group the European
Guidelines recommend to preform molecular analysis for UTUC patients
susceptible for hereditary background based on four criteria: (I) UTUC
diagnosis before the age of 60 years; (II) personal history of
HNPCC-spectrum cancer; (III) at least one first-degree relative
diagnosed with HNPCC under the age of 50 years; or (IV) two first-degree
relatives with known HNPCC (without age restriction) (3). The molecular analysis aims to detect loss of MMR function by using immunostaining of MMR genes (hMLH1, hMSH2),
DNA sequencing and microsatellite instability analysis. The loss of MMR
function is associated with the resistance against chemotherapeutic
agents with DNA-damaging effect (cisplatin, 5-fluorouracil, doxorubicin
etc.) (26).
The most frequently used radical surgical treatment of UTUC leads to
the loss of kidney function that strongly limits the use of
chemotherapies. Therefore, the prediction, of which patient will benefit
from chemotherapy, is even more important in UTUC than in UBC.
In accordance, UTUC grade more accurately predicts survival at initial biopsy as tumor stage (35)......
Open radical surgery
For
high-risk UTUC similar to UBC open radical surgery is the standard of
care. However, the management of lymph nodes regarding both extent and
templates are much more controversial for UTUC patients (63,65,66)....
abstract The American Society of Peritoneal Surface Malignancies Multi-Institution evaluation of 1,051 advanced ovarian cancer patients undergoing cytoreductive surgery and HIPEC: An introduction of the peritoneal surface disease severity score
Background
Standard
treatment for ovarian epithelial cancer (OEC) consists of cytoreductive
surgery (CRS) and a platinum–taxane chemotherapy combination. There is
increasing interest in evaluating hyperthermic intraperitoneal
chemotherapy (HIPEC) in patients with stage IIIC/IV disease. The peritoneal surface disease severity score (PSDSS) was introduced as a
basis to improve patient selection for this therapy in OEC.
Methods
The
charts of 1,051 patients with advanced OEC who underwent CRS/HIPEC were
retrospectively evaluated using the following preoperatively obtained
criteria: symptoms, peritoneal dissemination, and tumor histology.
Overall survival was analyzed according to PSDSS as well as the timings
and agents used during CRS/HIPEC.
Results
Median
survival for all 1,051 patients was 73.4 months. PSDSS information was
available for 553 patients. Survival correlated negatively with PSDSS (P < 0.001).
Furthermore, combining PSDSS scores into I/II and III/IV described two
distinct patient populations with vastly different outcomes, 100 versus
55 months, respectively (P < 0.001). Multivariate analysis failed to describe any differences between timings of HIPEC or chemotherapy agents used.
Conclusion
PSDSS
was capable of identifying a better surviving patient population in
advanced-stage OEC. While randomized trials to evaluate the benefit of
HIPEC are needed, the PSDSS may be a useful tool for selecting and
stratifying OEC patients in clinical trials.
open access Bevacizumab combined with chemotherapy for ovarian cancer: an updated systematic review and meta-analysis of randomized controlled trials
Literature search and inclusion criteria
The
literature search focused on randomized controlled trials published
from database inception to May 2016. Studies comparing bevacizumab plus
chemotherapy with chemotherapy alone were eligible for inclusion. We
searched the PubMed, EMBASE, Web of Science and Central (Cochrane
clinical trials database) databases, and we also searched
clinicaltrial.gov. We used the search terms “bevacizumab”, “Avastin”,
“chemotherapy”, and “ovarian cancer” in various combinations. In
addition, only phase III randomized trials were restricted in the search
strategy. The language of an article published was not restricted.
CONCLUSIONS
This
updated meta-analysis indicates that bevacizumab combined with
chemotherapy significantly improved PFS and OS in both patients with
high-risk of progression and patients with recurrent OC, with an
increased incidence of common adverse events. However, no statistically
significant survival benefit was identified in the front-line settings.
ORR is improved in overall population by the addition of bevacizumab.
Cancer screening barriers and facilitators for under and never screened populations: A mixed methods study
Highlights
•
Significant barriers to cancer screening relate to the universal human condition of fear.
•
Significant facilitators for cancer screening are related to relationship and communication.
•
The top barriers and facilitators are consistent across the three cancers and upscale from local to provincial levels.
Background
Cancer
screening is below targets in Ontario, Canada. Our objective was to
identify and quantify the barriers and facilitators for breast, cervical
and colorectal cancer screening for under and never screened (UNS)
residents living in Ontario between 2011 and 2013.
Methods
We
used a multi-phased mixed methods study design. Results from thematic
analysis of focus group discussions with health care providers and UNS
community members were used to develop an on-line, province-wide,
cross-sectional survey to estimate the prevalence of barriers and
facilitators for the provincial population. Adjusted prevalence odds
ratios and 95% confidence intervals were estimated for UNS compared to
regularly screened participants using logistic regression.
Results
Four
focus groups were held with health service providers and sixteen with
UNS community members. Top barriers and facilitators themed around
provider-patient communication, fear and embarrassment, history of
physical or sexual abuse, social determinants of health (including low
literacy, lack of awareness, and health insurance), symptoms appearing,
and family and friends. 3075 participants completed the online survey.
Compared to regularly screened participants, UNS had significantly
higher odds of reporting: no regular health care provider; not feeling
comfortable talking about screening; or the Doctor or Nurse Practitioner
not suggesting screening. UNS also had significantly higher odds of
reporting the facilitators: the test being less scary/painful or
uncomfortable; friend/family insisting on getting screened; starting to
have symptoms; or an easier test that could be done at home.
Conclusions
Interventions addressing fear through individual, interpersonal and structural facilitators may increase cancer screening.
Black tea consumption may increase epithelial ovarian cancer risk.
•
The excess risk is most relevant for the endometrioid histotype.
•
Study strength: adult lifetime tea, coffee, and caffeinated beverage consumption.
•
Study Strength: evaluation of types of tea—caffeinated/black tea and green tea.
Background
The
risk for epithelial ovarian cancer associated with the consumption of
caffeinated beverages (tea, coffee, and soft drinks) and green tea is
inconclusive. However, few studies have investigated the type of
caffeinated beverage or the type of tea.
Objective
We
assessed consumption of tea (black/caffeinated tea and green tea
separately), coffee, and caffeinated soft drinks, as well as level of
consumption, and the risk for epithelial ovarian cancer and its
histotypes.
Study design
This
study was conducted within a population-based case-control study in
Alberta and British Columbia, Canada from 2001 to 2012. After
restricting to cases of epithelial invasive cancers and controls aged
40–79 years who completed an interview that included coffee, soft drink,
and tea consumption (ascertained starting in 2005 in British Columbia
and 2008 in Alberta), there were a total of 524 cases and 1587 controls.
Those that did not meet the threshold for beverage consumption (at
least once per month for 6 months or more) were classified as
non-drinkers. Adult lifetime cumulative consumption
(cup-years = cups/day * years) was calculated. Unconditional logistic
regression was used to estimate adjusted odds ratios (aOR) and 95%
confidence intervals (CI) to describe the association between the
relevant drink consumption and risk.
Results
No
excess risk was seen for coffee or caffeinated soft drinks. Similarly,
any tea consumption was not associated with risk, but when stratified by
the type of tea, there was an increase in risk in black tea only
drinkers (aOR = 1.56; 95% CI:1.07–2.28 for >40 cup-years), but no
excess risk for the exclusive green tea drinkers. Similar findings were
observed for post-menopausal women. The association for black tea only
consumption was mainly seen in the endometrioid histotype (aOR = 3.19;
95% CI: 1.32–7.69).
Conclusion
Black
tea consumption may be associated with an increased risk epithelial
ovarian carcinoma. The excess risk is seen only in the endometrioid
histotype but not in serous or clear cell. Further studies are required
to confirm these findings and identify the constituents in black tea
that may increase the risk.
The Undiagnosed Diseases Network (UDN) is a research study that is funded by the National Institutes of Health Common Fund .
Its purpose is to bring together clinical and research experts from
across the United States to solve the most challenging medical mysteries
using advanced technologies. Through this study, we hope to both
help individual patients and families and contribute to the
understanding of how the human body works. Requirements for Online Application
If you decide to apply for this study, you will need to answer a series of brief questions through our application portal, the UDN Gateway (link below), related to the following:
Contact information
Demographic information
Primary licensed healthcare provider information (name, address, phone, FAX, email)
Brief medical history questions
Previous evaluations
Travel limitations
A referral letter from a primary licensed healthcare
provider is also necessary in order to submit the online application to
the UDN. This referral letter must include:
A summary of the applicant’s medical problems
Date when symptoms were first noticed
Previous diagnoses
History of evaluations and testing
History of treatments and medications
Current medications
Family history
Healthcare provider’s diagnostic impressions
For pediatric patients, prenatal and birth history should also be provided.
After an application is complete and submitted in the Gateway,
applicants receive an email notification. The application is then sent
to one of the UDN clinical sites to review.
The UDN clinical sites typically contact applicants within one month
of application submission to request additional information, such as:
Medical records
Laboratory studies
MRI, X-ray, or CT images (can be sent on CD)
Photographs or videos
Pathology slides and reports
For pediatric patients: growth curves
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abstract
Cancer Epidemiology, Biomarkers & Prevention October 31,2016 Revision received October 19, 2016
Background: While high-risk mutations in identified major susceptibility
genes (DNA mismatch repair genes and MUTYH) account for some familial
aggregation of colorectal cancer, their population prevalence and the
causes of the remaining familial aggregation are not known. Methods: We studied the families of 5,744 colorectal cancer cases
(probands) recruited from population cancer registries in the USA,
Canada and Australia and screened probands for mutations in mismatch
repair genes and MUTYH. We conducted modified segregation analyses using
the cancer history of first-degree relatives, conditional on the
proband's age at diagnosis. We estimated the prevalence of mutations in
the identified genes, the prevalence of and hazard ratio for
unidentified major gene mutations, and the variance of the residual
polygenic component.
Results: We estimated that 1 in 279 of the population carry mutations
in mismatch repair genes (MLH1= 1 in 1946, MSH2= 1 in 2841, MSH6= 1 in
758, PMS2= 1 in 714), 1 in 45 carry mutations in MUTYH, and 1 in 504
carry mutations associated with an average 31-fold increased risk of
colorectal cancer in unidentified major genes. The estimated polygenic
variance was reduced by 30-50% after allowing for unidentified major
genes and decreased from 3.3 for age <40 years to 0.5 for age
{greater than or equal to}70 years (equivalent to sibling relative risks
of 5.1 to 1.3, respectively). Conclusions: Unidentified major genes might explain one-third to
one-half of the missing heritability of colorectal cancer. Impact: Our findings could aid gene discovery and development of better
colorectal cancer risk prediction models.
Concerns about patient safety and the potential for
medical error are largely unexplored for genetic testing, despite the
expansion of test use. In this preliminary qualitative study, we sought
the views of genetics professionals about error and patient safety
concerns in genomic medicine and factors that might mitigate them.
Methods:
Twelve semistructured interviews with experienced
genetics professionals were conducted. Transcripts were analyzed using
selective coding for issues related to error definition, mitigation, and
communication. Additional thematic analysis captured themes across
content categories.
Results:
Key informants suggested that the potential for adverse
events exists in all phases of genetic testing, from ordering to
analysis, interpretation, and follow-up. A perceived contributor was
lack of physician knowledge about genetics, resulting in errors in test
ordering and interpretation. The limitations and uncertainty inherent to
rapidly evolving technology were also seen as contributing factors.
Strategies to prevent errors included physician education, availability
of genetic experts for consultation, and enhanced communication such as
improved test reports and electronic decision support.
Conclusion:
Genetic testing poses concerns for patient safety due to
errors and the limitations of current tests. As genomic tests are
integrated into medical care, anticipating and addressing patient safety
concerns identified by these key informants will be crucial.
