Monday, April 08, 2013
Risk of hypothyroidism in patients with cancer treated with sunitinib: A systematic review and meta-analysis
Abstract
Background.
The multitargeted tyrosine kinase inhibitor sunitinib is used in
various cancers. Clinical studies have reported a substantial variation
in the incidence of hypothyroidism associated with sunitinib, without a
systemic attempt to synthesize these data.
Methods. We searched
Medline databases for relevant clinical trials published up to May 2012.
Phase II and III trials and expanded access programs of sunitinib in
patients with any type of cancer that reported occurrence of
hypothyroidism were eligible. The summary incidence, relative risk (RR)
and 95% confidence intervals (CIs) were calculated using random- or
fixed-effects models based on the heterogeneity of included studies.
The Incidence of Endometrial Cancer in Women with BRCA1 and BRCA2 Mutations: an International Prospective Cohort Study
Abstract
- •
- The risk of endometrial cancer is higher in BRCA1 mutation carriers than in the general population.
- •
- Tamoxifen use is associated with an increase in the risk of endometrial cancer in BRCA1 and BRCA2 carriers.
- •
- A course of tamoxifen is associated with a two percent risk of endometrial cancer
Objective
To evaluate the risk of endometrial cancer in women who carry a mutation in the BRCA1 or the BRCA2 gene.
Methods
We followed 4,456 women with a BRCA1 or a BRCA2
mutation for incident cases of endometrial cancer. The incidence of
endometrial cancer was estimated per 100,000 women/per year. The hazard
ratios for endometrial cancer were estimated by calculating standardized
incidence ratios (SIR) according to age group and country of residence.
We estimated the impact of tamoxifen and hormone replacement therapy on
the incidence of endometrial cancer in BRCA1 and BRCA2 carriers.
Sunday, April 07, 2013
press release: Some patients with incurable tumors and BRCA mutations respond to new 2-drug combination (sapacitabine and seliciclib)
Press release:
WASHINGTON–A novel combination of two drugs has shown anti-cancer activity in patients who had incurable solid tumors and carried a germline mutation in their BRCA genes, Dana-Farber Cancer Institute researchers are reporting at the American Association for Cancer Research annual meeting in Washington, April 6-10.
The findings (abstract LB-202) will be released at a press conference on Sunday, April 7, 2 p.m. ET, and later at an oral presentation on Tuesday, April 9, 2 p.m. ET, in Room 153, in the Washington Convention Center.
The two oral drugs, sapacitabine and seliciclib, were given sequentially in a phase 1 clinical trial that is mainly enrolling patients whose tumors lack BRCA function because of an inherited mutation.
"We have seen several responses among these patients, as well as instances of prolonged stable disease lasting more than a year," said Geoffrey Shapiro, MD, PhD, director of Dana-Farber's Early Drug Development Center (EDDC). As a result, he said that a BRCA mutation may be a potential biomarker that identifies patients who are more likely to respond to the drug combination.
Sixteen patients enrolled in the trial carried an inherited BRCA mutation. Four of these patients had partial responses – a 30 percent or greater shrinkage of tumor mass – including one with pancreatic, two with breast, and one with ovarian cancer. Three patients were continuing to have a partial response at the time of presentation of the data, with the longest lasting more than 78 weeks. Two additional BRCA mutation carriers, with breast and ovarian cancer, experienced stable disease for 21 and 64 weeks, respectively. Of the remaining 22 patients enrolled in the trial, six experienced stable disease for 12 weeks or more.
Sapacitabine is toxic to cancer cells by causing damage to their DNA, which, if not repaired, causes the cells to self-destruct. The BRCA protein is essential for repair of the DNA damage caused by sapacitabine, so patients with mutations that inactivate BRCA may be more sensitive to the drug's activity.
The second drug, seliciclib, is an inhibitor of cyclin-dependent kinases (CDKs), enzymes that have multiple cellular functions, including a role in DNA repair, further augmenting the effects of sapacitabine. The patients in the trial received sapacitabine twice daily for seven days, followed by seliciclib twice daily for three days. Adverse events were mild to moderate in intensity, the study found.
Shapiro and colleagues are continuing to enroll BRCA mutation carriers in the trial, and hope to determine if the mutations may serve as a biomarker for response. He said that these drugs may prove to be an important treatment alternative for patients with BRCA-deficient cancers.
open access: Control Group Design: Enhancing Rigor in Research of Mind-Body Therapies for Depression
open access
In conclusion, the state of the science in mind-body research is that every systematic review has identified the need for better methodology and more well-controlled studies. Considering the challenge in developing optimal controls, we began with a brief focused review of control groups used in pharmaceutical research. Given that the pharmaceutical sector’s gold standard of randomized and double-blinded design does not typically apply in mind-body therapy research, we briefly reviewed the types of control groups used in the literature on yoga and tai chi for depression. To address the methodological challenges of research on mind-body modalities, we have reviewed key questions researchers should ask when designing control groups and we have suggested multiple ways to minimize bias and maximize validity. We have focused our discussion and recommendations based upon research of two types of mind-body interventions, yoga and tai chi, for depression. However, the recommendations here may be appropriately applied in other modalities and conditions typically examined in complementary and alternative therapy research. Although we acknowledge that these methods are not the only ways for minimizing complications, we expect that this paper begins the discussion amongst our research colleagues about these and other methods for optimal research study design.
open access: Ganoderma tsugae Extract Inhibits Growth of HER2-Overexpressing Cancer Cells via Modulation of HER2/PI3K/Akt Signaling Pathway
open access
In conclusion, we provide a schematic presentation of possible molecular mechanisms in vitro and in vivo for the inhibitory effects of GTE on the proliferation of HER2-overexpressing cancer cells (Figure 6). Our results indicate that GTE induces G1 cell cycle arrest via regulation of the HER2/PI3K/Akt signaling pathway, thereby leading to a reduction in the growth of cancer cells overexpressing HER2. Our data also demonstrate that the depletion of HER2 protein by GTE involves an inhibition in the transcriptional activity of the HER2 gene and an increase in the proteasome-dependent degradation of the HER2 protein. In addition, we have also shown that a combination of GTE with anticancer drugs (e.g., taxol, cisplatin, and doxorubicin) exerts synergistic growth-inhibitory effect on HER2-overexpressing cancer cells. Taken together, our findings suggest that GTE may be a useful and effective adjuvant therapeutic agent for the treatment of cancers that highly express HER2.
open access: Why Urban Citizens in Developing Countries Use Traditional Medicines: The Case of Suriname
Blogger's Note: interesting/worth reading - references Europe, U.S...
open access
".....The outcome of our study that illness and (the transfer of) traditional knowledge are the reasons why urban citizens in Suriname use TMs (traditional medicines), rather than poverty or a limited access to modern health care, might be more universal than previously thought. The continued use of medicinal plants in urban areas, where biomedical health care is available to most citizens, has not only been observed in cities in developing countries [14, 16–18], but also among international migrant communities in USA and Europe [8, 9, 11, 46, 51]. The general idea that traditional knowledge will disappear when people enter the market society [32] is challenged by the popularity of self-medication with medicinal plant use in large urban areas [51]. Research on the potential risks and benefits of traditional medicines should therefore be put prominently on the global public health agenda....."
Hope in Newly Diagnosed Cancer Patients
Abstract
Context
Hope
is important to cancer patients as it helps them deal with their
diagnosis. Little is known about hope in newly diagnosed cancer
patients.
Objectives
Based
on the Transcending Possibilities conceptual model of hope, the purpose
of this study was to examine the relationship of hope with pain, energy,
and psychological and demographic characteristics in newly diagnosed
adult oncology outpatients.
Methods
Data
from 310 New Patient Assessment Forms from cancer outpatients' health
records were collected. Health records from the first six months of 2009
were reviewed and data were collected on hope, energy, pain,
depression, anxiety, feeling overwhelmed, and demographic variables....
Results
Hope scores were significantly negatively related to age (P = 0.02).
More specifically, oncology patients who were 65 years of age or older
had significantly less hope than those under the age of 65 years (P = 0.01). Gender (P = 0.009) also was a significant factor, with men having higher hope scores than women. No other variables were significant.
Conclusion
Older
adults comprise the majority of persons in Canada with cancer. The
lower hope scores found in this age group compared with their younger
counterparts underscore the importance of further research. This study
provides a foundation for future research in this important area for
oncology patients.
Breakthrough Cancer Pain: An Observational Study of 1000 European Oncology Patients
Abstract
Context
Breakthrough pain is common in patients with cancer and is a significant cause of morbidity in this group of patients.
Objectives
The aim of this study was to characterize breakthrough pain in a diverse population of cancer patients.
Methods
The
study involved 1000 cancer patients from 13 European countries.
Patients were screened for breakthrough pain using a recommended
diagnostic algorithm and then questioned about the characteristics and
management of their pain.
Results
Of
the 1000 patients, 44% reported incident pain, 41.5% spontaneous pain,
and 14.5% a combination. The median number of episodes was three a day.
The median time to peak intensity was 10 minutes, with the median for
patients with incident pain being five minutes (P < 0.001).
The median duration of untreated episodes was 60 minutes, with the
median for patients with incident pain being 45 minutes (P = 0.001).
Eight hundred six patients stated that pain stopped them doing
something, 66 that it sometimes stopped them doing something, and only
107 that it did not interfere with their activities. Patients with
incident pain reported more interference with walking ability and normal
work, whereas patients with spontaneous pain reported more interference
with mood and sleep. As well, 65.5% of patients could identify an
intervention that improved their pain (29.5%, pharmacological; 23%,
nonpharmacological; 12%, combination). Regarding medications, 980
patients were receiving an opioid to treat their pain, although only 191
patients were receiving a transmucosal fentanyl product licensed for
the treatment of breakthrough pain.
Conclusion
Breakthrough cancer pain is an extremely heterogeneous condition.
Placebo and Nocebo Effects in RCCTs: The Implications for Research and Practice (ketamine)
Abstract
Special Article
Placebo
and nocebo effects are known to contribute significantly to the
response to symptom control, including analgesia. Clinical trial
methodologies using placebo controls are designed to identify the
magnitude of these effects in the research context. An adequately
powered, randomized, double-blind, placebo-controlled trial of ketamine
in cancer pain has recently been reported, which demonstrated no net
clinical benefit for ketamine over and above that of placebo. Rates of
placebo and nocebo responses were high. The setting of a clinical trial
provides an opportunity to quantify the nonpharmacologic aspects of
patient responses to analgesia, raising important clinical and ethical
issues for practice. The findings of the ketamine study are analyzed in
the context of a methodological discussion of placebo and nocebo
effects, what is known about the biological and psychological bases for
each of these, and their implications for a clinical trial design in the
palliative care setting. Along with reviewing the use of ketamine after
this negative trial, clinicians need to remain aware of the strength
and significance of both placebo and nocebo responses in their own
practices and the biopsychosocial complexity of why and how patients
actually respond to pain management strategies. The results of this
study strongly reinforce the importance of the therapeutic relationship
and the context of care.
DNA copy number profiling reveals extensive genomic loss in hereditary BRCA1 and BRCA2 OVARIAN carcinomas (and PARP inhibitors)
Abstract
Background:
Few
studies have attempted to characterise genomic changes occurring in
hereditary epithelial ovarian carcinomas (EOCs) and inconsistent results
have been obtained. Given the relevance of DNA copy number alterations
in ovarian oncogenesis and growing clinical implications of the
BRCA-gene status, we aimed to characterise the genomic profiles of
hereditary and sporadic ovarian tumours.
Conclusion:
Somatic
alterations occurring in the development of familial EOCs do not differ
substantially from the ones occurring in sporadic carcinomas. However,
some specific features like extensive genomic loss observed in BRCA1/2 tumours may be of clinical relevance helping to identify BRCA-related patients likely to respond to PARP inhibitors.
Access : Triple-negative breast cancer: BRCAness and concordance of clinical features with BRCA1-mutation carriers : British Journal of Cancer
Abstract
Conclusion:
The majority of the TNBCs
show BRCAness, and those tumours share clinicopathological
characteristics with BRCA1-mutated tumours. A better characterisation of
TNBC and the presence of BRCAness could have consequences for both
hereditary breast cancer screening and the treatment of these tumours.
Attitudes About Regulation Among Direct-to-Consumer Genetic Testing Customers | Abstract
Abstract
Introduction:
The first regulatory rulings by the U.S. Food and Drug Administration
on direct-to-consumer (DTC) genetic testing services are expected soon.
As the process of regulating these and other genetic tests moves ahead,
it is important to understand the preferences of DTC genetic testing
customers about the regulation of these products. Methods: An
online survey of customers of three DTC genetic testing companies was
conducted 2–8 months after they had received their results. Participants
were asked about the importance of regulating the companies selling DTC
genetic tests.
Results: Most of the 1,046 respondents responded
that it would be important to have a nongovernmental (84%) or
governmental agency (73%) monitor DTC companies' claims to ensure the
consistency with scientific evidence. However, 66% also felt that it was
important that DTC tests be available without governmental oversight.
Nearly, all customers favored a policy to ensure that insurers and law
enforcement officials could not access their information.
Discussion:
Although many DTC customers want access to genetic testing services
without restrictions imposed by the government regulation, most also
favor an organization operating alongside DTC companies that will ensure
that the claims made by the companies are consistent with sound
scientific evidence. This seeming contradiction may indicate that DTC
customers want to ensure that they have unfettered access to
high-quality information. Additionally, policies to help ensure privacy
of data would be welcomed by customers, despite relatively high
confidence in the companies.
press release: 2-step ovarian cancer immunotherapy made from patients' own tumor shows promise
press release
Trial benefits three-quarters of patients
WASHINGTON, D.C. — As many as three quarters of advanced ovarian cancer patients appeared to respond to a new two-step immunotherapy approach -- including one patient who achieved complete remission -- according research from the Perelman School of Medicine at the University of Pennsylvania that will be presented today in a press conference at the AACR Annual Meeting 2013 (Presentation #LB-335).
The immunotherapy has two steps – a personalized dendritic cell vaccination and adoptive T-cell therapy. The team reports that in the study of 31 patients, vaccination therapy alone showed about a 61 percent clinical benefit, and the combination of both therapies showed about a 75 percent benefit.....
..... "This is the first time such a combination immunotherapy approach has been used for patients with ovarian cancer, and we believe the results are leading us toward a completely new way to treat this disease." Both treatments are given in conjunction with bevacizumab, a drug that controls the blood vessel growth that feeds tumors. Combining bevacizumab with immunotherapy makes a powerful duo, Kandalaft says. The vaccine trial is still open to accrual to test new combinatorial strategies.
press release: Targeted toxin active in platinum-resistant ovarian cancers (DMUC5754A)
Targeted toxin active in platinum-resistant ovarian cancers
WASHINGTON -- A new antibody-guided drug has shown promising activity in a phase I trial involving ovarian cancer patients with platinum drug-resistant disease, researchers from Dana-Farber Cancer Institute will report today at the annual meeting of the American Association for Cancer Research. The findings (abstract LB-290) will be discussed at a press conference on Saturday, April 06, 2013, 1:00 p.m., ET, in Room 153, in the Washington Convention Center and later at an oral presentation on Tuesday, April 09, 2013, 4:00 p.m. to 4:20 p.m. in room 146, in the Washington Convention Center.
Joyce Liu, MD, MPH, first author of the study, said that among 29 patients who received the antibody-drug conjugate at what was found to be the maximum tolerated dose, there was one complete response and four partial responses. "In addition, there were additional patients with prolonged stable disease who were able to stay on treatment," said Liu, of the gynecologic oncology treatment center at Dana-Farber.
The responses all occurred in patients whose tumors had high expression of the MUC16 protein to which the drug is targeted. Known as DMUC5754A, the drug conjugate consists of an antibody, which recognizes the MUC16 protein expressed by ovarian cancer cells, fused to a toxin, MMAE, which prevents cancer cells from dividing. Targeting the drug conjugate specifically to ovarian cancer cells reduced adverse effects of the toxin on healthy tissues and organs, said Liu. She called the safety profile "encouraging." Most common adverse effects were fatigue, nausea, and vomiting. This phase 1 multicenter trial is the first use in humans of DMUC5754A, and the responses, which Liu called "a nice sign of activity in a very challenging type of ovarian cancer to treat," merit further testing in a phase II trial, which is being planned. "If the activity of this drug is confirmed in additional trials, this will represent a novel type of therapy for ovarian cancer," Liu said.....
Wit (play)
Blogger's Note: this (now) highly acclaimed play was first brought to the public and academic health centers in 1995 amid much controversy and criticism
Wit (play) - Wikipedia
Wit (also styled as W;t) is a one-act play written by American playwright Margaret Edson, which won the 1999 Pulitzer Prize for Drama. Edson used her work experience in a hospital as part of the inspiration for her play.[1][2]
Synopsis
The action of the play takes place during the final hours of Dr Vivian Bearing, a university professor of English, dying of ovarian cancer. She recalls the initial diagnosis of Stage IV metastatic ovarian cancer from her oncologist, Dr Harvey Kelekian. Dr Kelekian then proposes an experimental chemotherapeutic treatment regimen consisting of eight rounds at full dosage. Vivian agrees to the treatment.Over the course of the play, Vivian reflects on her life through the intricacies of the English language, especially the use of wit in the metaphysical poetry of John Donne. Throughout the play, she recites Donne's Holy Sonnet X, "Death Be Not Proud," while reflecting upon her condition. (In the revised edition of John Donne's Holy Sonnets, "If Poysonous Mineralls" and "Death Be Not Proud" are sonnets V and VI, respectively.) As a professor, she has a reputation for rigorous teaching methods. She has lived her life alone, is unmarried and without children, her parents are deceased, and she has no emergency contact.
Vivian recalls undergoing tests by various medical technicians and being the subject of grand rounds. She remembers sharing a love of language and books with her father. She flashes back to her experiences as a student of Dr E. M. Ashford, an expert on John Donne. Bearing later finds herself under the care of Dr Jason Posner, an oncology research fellow who has taken her class on John Donne. At the hospital, she recognizes that doctors are interested in her for her research value and, like her, tend to ignore humanity in favor of knowledge. Gradually, she realizes that she would prefer kindness to intellectualism.
Vivian reaches the end stage in extreme pain as Susie Monahan, a nurse at the medical centre, offers Vivian compassion and discusses with her the option of exercising her final option, "do not resuscitate" (DNR), in case of a severe decline in her condition. Vivian decides to mark the DNR option. Dr Ashford, in town for her great-grandson's birthday, visits the hospital after learning of Vivian's cancer. She comforts her and offers to read a Donne sonnet, but Vivian, scarcely conscious, declines. Instead, Ashford reads from Margaret Wise Brown's The Runaway Bunny, which she had bought for her great-grandson.
When Vivian flatlines, Jason tries to resuscitate her, and calls in a medical team to administer CPR. Susie tries to stop him, pointing out the DNR instruction. Jason eventually realizes his mistake and calls for the CPR team to stop. The play ends as Vivian, unclothed after her death, walks from her hospital bed "toward a little light"......
(note: the movie 'Wit') The perception of shared medical decision making of expert and lay people: Effects of observing a movie clip depicting a medical consultation
Abstract
Objective
To
test for differences between experts and lay people in assessment of
the degree to which a doctor engaged in a shared decision making (SDM)
with a patient using the OPTION scale and a movie clip as stimulus
material.
Methods
A segment of
the movie ‘Wit’, depicting the communication of the diagnosis and the
therapy proposed of a cancer (ovarian cancer) , was shown to (a) university students with
no knowledge about doctor–patient communication; (b) nurses working in
medicine departments; (c) advanced medical students; (d) hospital
physicians. The participants were asked to complete the OPTION scale
which measures the extent to which physicians involve patients in
medical decisions. An analysis of variance was used to compare OPTION
scores across the four groups and to compare males and females.
Results
Being female [F(1,190) = 11.9; p < .001] and being familiar with medical issues [F(3,190) = 11.09; p < .001]
were both significantly associated with a negative evaluations of the
doctor's ability to involve the patient in the SDM.
Conclusion
Lay people and males (including male experts), are less demanding regarding SDM abilities.
Practice implications
A
more systematic use of videos and the OPTION scale as validated outcome
measure could be helpful educational strategy for the teaching of SDM.
Quantitative multiparametric MRI of ovarian cancer
Abstract
PURPOSE:
To identify parameters associated with ovarian malignancy using multiparametric quantitative magnetic resonance imaging (MRI).CONCLUSION:
Quantitative parameters from DCE-MRI and T2 mapping can differentiate benign from malignant ovarian masses
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