Hematological Toxicity After Robotic Stereotactic Body Radiosurgery for Treatment of Metastatic Gynecologic Malignancies
published online 30 April 2012.
Monday, April 30, 2012
paywalled: Hematological Toxicity After Robotic Stereotactic Body Radiosurgery for Treatment of Metastatic Gynecologic Malignancies
Hematological Toxicity After Robotic Stereotactic Body Radiosurgery for Treatment of Metastatic Gynecologic Malignancies
published online 30 April 2012.
Journal of Experimental & Clinical Cancer Research | Abstract | Circulating microRNAs in cancer: origin, function and application
Journal of Experimental & Clinical Cancer Research | Abstract | Circulating microRNAs in cancer: origin, function and application
The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.
ReviewCirculating microRNAs in cancer: origin, function and application
Published: 30 April 2012
Abstract (provisional)
MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression
at the posttranscriptional level. The dysregulation of miRNAs has been linked to a
series of diseases, including various types of cancer. Since their discovery in the
circulation of cancer patients, there has been a steady increase in the study of circulating
miRNAs as stable, non-invasive biomarkers. However, the origin and function of circulating
miRNAs has not been systematically elucidated. In this review, we summarize the discovery
of circulating miRNAs and their potential as biomarkers. We further emphasize their
possible origin and function. Finally, we discuss the application and existing questions
surrounding circulating miRNAs in cancer diagnostics. Although several challenges
remain to be concerned, circulating miRNAs could be useful, non-invasive biomarkers
for cancer diagnosis.
The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.
Biomarkers in the circulation
"Circulating biomarkers undoubtedly play an increasingly significant role in clinicalapplications such as disease diagnostics, monitoring therapeutic effect and predicting recurrence in cancer patients. The currently used fluid-based biomarkers are primarily proteins, such as alpha-fetoprotein (AFP) [8], chromogranin A (CgA) [9], nuclear matrix
protein 22 (NMP 22) [10], carbohydrate antigen 125 (CA 125) [11]; enzymes, such as prostate specific antigen (PSA) [12]; and human chorionic gonadotropin (hCG) [13]. While these biomarkers provide an opportunity to analyze tumors comprehensively in an invasive
way, low sensitivity and specificity limit their clinical application. For example, serum levels of AFP are often elevated in hepatocellular carcinoma (HCC); however, this is also the case in germ cell tumors, gastric, biliary and pancreatic cancers.......
reference/cited (google):
23. Resnick KE, Alder H, Hagan JP, Richardson DL, Croce CM, Cohn DE: The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol Oncol 2009, 112:55–59.
paywalled: Individuals at high-risk for pancreatic cancer development: Management options and the role of surgery (Lynch Syndrome, breast/ovarian BRCA 2....)
Blogger's Note: while full access is by subscription only, key words indicate 'high risk' categories not limited to Lynch Syndrome, BRCA 2; BRCA 2 - blogger's assumption based on genetics in absence of full text acccess)
Individuals at high-risk for pancreatic cancer development: Management options and the role of surgery
Abstract
Pancreatic cancer (PC) is a highly lethal disease. Despite advances regarding the safety and long-term results of pancreatectomies, early diagnosis remains the only hope for cure. This necessitates the implementation of an intensive screening program (based mainly on modern imaging), which – given the incidence of PC – is not cost effective for the general population. However, this screening program is recommended for individuals at high-risk for PC development.Indications for screening include the following three clinical settings: hereditary cancer predisposition syndromes associated with PC, hereditary pancreatitis and familial pancreatic cancer syndrome. The aim of this strategy is to identify pre-invasive (precursor) lesions, which are curable. Surgery is recommended in the presence of recognizable lesion on imaging lesions. Partial (anatomic) pancreatectomy – depending on the location of the suspicious lesion – is the most widely accepted type of surgical intervention in this setting; occasionally, however, total pancreatectomy may be required, in carefully selected patients. Despite that experience still remains limited, there is evidence that this aggressive strategy allows early detection of neoplastic lesions, thereby improving the effectiveness of surgery and prognosis.
Keywords: Pancreas, Surgery, Cancer, PanIN, MCN, IPMN, Pancreatectomy, Total pancreatectomy, Screening
Abbreviations: PanIN, pancreatic intraepithelial neoplasia, IPMN, intraductal papillary mucinous neoplasm, MCN, mucinous cystic neoplasm, PJS, Peutz–Jeghers syndrome, FAMMM syndrome, familial atypical multiple mole melanoma syndrome, HNPCC, hereditary non-polyposis colon cancer (Lynch syndrome), HOBC, hereditary ovarian and breast cancer, VHL, von Hippel–Lindau, PD, pancreatoduodenectomy
financial news UK: Horizon lines up $multi-million cancer drug boom | Business Weekly | Technology | Biotechnology | Business news | Cambridge and the East of England
Horizon lines up $multi-million cancer drug boom | Business Weekly | Technology | Biotechnology | Business news
Horizon lines up $multi-million cancer drug boom
The UK pioneer is partnering US biopharma company H3 Biomedicine Inc in the venture. And Japanese giant Eisai, which has its European Knowledge Centre in Hatfield, will conduct any resulting clinical trials......Markus Warmuth, president and CEO, H3 Biomedicine said that the successful development of new personalised medicines depended on well validated and characterised targets and clearly defined patient populations.
“High attrition rates in clinical trials have been impacting industry for a while,” he said. “We believe that clinical success starts at target selection and validation.
“We have elected to work with Horizon because its tools will enable us to progress toward identifying the best possible targets for new drugs with the power to have meaningful therapeutic relevance. That may help us to increase clinical success rates and expedite the delivery of new therapies to the patients who need them.”
paywalled: Intrapleural paclitaxel for malignant pleural effusion from ovarian and breast cancer: a phase II study with pharmacokinetic analysis.
Intrapleural paclitaxel for malig... [Cancer Chemother Pharmacol. 2012] - PubMed - NCBI
Intrapleural paclitaxel for malignant pleural effusion from ovarian and breast cancer: a phase II study with pharmacokinetic analysis.
Abstract
INTRODUCTION:
Malignant pleural effusion (MPE) is a frequent complication in many types of tumors diminishing the patient's ability to perform activities. Despite various studies on talc treatment, some doubts about its safety and effectiveness remain, so the search for a more ideal intrapleural agent continues. We analyzed the effectiveness and safety of intrapleural paclitaxel in ovarian and breast cancer patients.CONCLUSION:
Intrapleural paclitaxel is a safe and effective palliative treatment for MPE from breast and ovarian cancers and may be integrated with systemic chemotherapy.Sunday, April 29, 2012
paywalled: Is comprehensive surgical staging needed for thorough evaluation of early-stage ovarian carcinoma?
Blogger's Note: a repost
Is comprehensive surgical staging needed... [Am J Obstet Gynecol. 2012] - PubMed - NCBI
Is comprehensive surgical staging needed for thorough evaluation of early-stage ovarian carcinoma?
Abstract
OBJECTIVE:
Patients with ovarian cancer may have occult metastasis at the time of surgery. Our purpose was to determine the prevalence and sites of occult metastasis in epithelial ovarian cancer grossly confined to the ovary and examine the significance of routine omentectomy and peritoneal biopsies as part of a comprehensive staging procedure.STUDY DESIGN:
Data were retrospectively abstracted from patients presenting to University of Texas Southwestern Medical Center Hospitals from 1993 through 2009 with ovarian cancer without gross spread beyond the ovary who underwent comprehensive surgical staging.RESULTS:
A total of 86
patients with ovarian cancer grossly confined to the ovary who underwent
complete surgical staging were identified. Of patients, 29% were
upstaged following comprehensive surgical staging; 6% had metastatic
disease in uterus and/or fallopian tubes, 6% in lymph nodes, and 17% in
peritoneal, omental, or adhesion biopsies.
CONCLUSION:
Patients with epithelial ovarian cancer should continue to undergo comprehensive surgical staging, since it identifies occult metastasis in a significant number of patients.EvidenceUpdates: Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials including professional commentaries
Blogger's Note: registration is free, the benefit of this secondary site (BMJ) is the addition of professional comments
This month's most accessed articles -- EvidenceUpdates
Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials
paywalled: Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials : The Lancet
Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials : The Lancet
Summary
Background
Daily
aspirin reduces the long-term risk of death due to cancer. However, the
short-term effect is less certain, especially in women, effects on
cancer incidence are largely unknown, and the time course of risk and
benefit in primary prevention is unclear. We studied cancer deaths in
all trials of daily aspirin versus control and the time course of
effects of low-dose aspirin on cancer incidence and other outcomes in
trials in primary prevention.
Interpretation
Alongside
the previously reported reduction by aspirin of the long-term risk of
cancer death, the short-term reductions in cancer incidence and
mortality and the decrease in risk of major extracranial bleeds with
extended use, and their low case-fatality, add to the case for daily
aspirin in prevention of cancer.
paywalled: PET/CT scanning guided intensity-modulated radiotherapy in treatment of recurrent ovarian cancer.
PET/CT scanning guided intensity-modulated radi... [Eur J Radiol. 2012] - PubMed - NCBI
Abstract
OBJECTIVE:
This study was undertaken to evaluate the clinical contribution of positron emission tomography using (18)F-fluorodeoxyglucose and integrated computer tomography (FDG-PET/CT) guided intensity-modulated radiotherapy (IMRT) for treatment of recurrent ovarian cancer.MATERIALS AND METHODS:
Fifty-eight patients with recurrent ovarian cancer from 2003 to 2008 were retrospectively studied. In these patients, 28 received PET/CT guided IMRT (PET/CT-IMRT group), and 30 received CT guided IMRT (CT-IMRT group). Treatment plans, tumor response, toxicities and survival were evaluated.RESULTS:
Changes in GTV delineation were found in 10 (35.7%) patients based on PET-CT information compared with CT data, due to the incorporation of additional lymph node metastases and extension of the metastasis tumor. PET/CT guided IMRT improved tumor response compared to CT-IMRT group (CR: 64.3% vs. 46.7%, P=0.021; PR: 25.0% vs. 13.3%, P=0.036). The 3-year overall survival was significantly higher in the PET-CT/IMRT group than control (34.1% vs. 13.2%, P=0.014).CONCLUSIONS:
PET/CT guided IMRT in recurrent
ovarian cancer patients improved the delineation of GTV and reduce the
likelihood of geographic misses and therefore improve the clinical
outcome.
paywalled: Low-dose non-enhanced CT versus full-dose contrast-enhanced CT in integrated PET/CT scans for diagnosing ovarian cancer recurrence
Low-dose non-enhanced CT versus full-dose contr... [Eur J Radiol. 2012] - PubMed - NCBI
Abstract
OBJECTIVE:
To evaluate low-dose non-enhanced CT (ldCT) and full-dose contrast-enhanced CT (ceCT) in integrated (18)F-fluorodeoxyglucose (FDG)-PET/CT studies for restaging of ovarian cancer.MATERIALS AND METHODS:
One hundred and twenty women who had undergone treatment for ovarian cancer underwent a conventional PET/CT scans with ldCT, and then ceCT. Two observers interpreted and decided in consensus on the PET/ldCT and PET/ceCT images by a 3-point scale (N: negative, E: equivocal, P: positive) per patient and lesion site. Final diagnoses were obtained by histopathological examinations, or clinical follow-up for at least 6 months.RESULTS:
Patient-based analysis showed that the sensitivity, specificity, and accuracy of PET/ceCT was 86.9% (40/46), 95.9% (71/74), and 92.5% (111/120), respectively, whereas those of PET/ldCT were 78.3% (36/46), 95.0% (70/74), and 88.3% (106/120), respectively. All sensitivity, specificity, and accuracy significantly differed between two methods ...... The scales of detecting 104 recurrent lesion sites were N:14, E:6, P:84 for PET/ceCT, and N:15, E:17, P:72 for PET/ldCT, respectively. Eleven equivocal and one negative regions by PET/ldCT were correctly interpreted as positive by PET/ceCT.CONCLUSION:
PET/ceCT is a more accurate imaging modality with higher confidence for assessing ovarian cancer recurrence than PET/ldCT.
Commentary: Does aspirin really reduce the risk of colon cancer? : The Lancet
Does aspirin really reduce the risk of colon cancer? : The Lancet
Does aspirin really reduce the risk of colon cancer?
The study by John Burn and colleagues1
is unquestionably a superb piece of work that opens the door to
formalised chemoprevention in young carriers of Lynch syndrome. However,
setting aside the fact that the primary intention-to-treat analysis was
not significant, there is a need to address whether these data are
applicable to others at need of chemoprevention.
Specifically,
the study included a predominantly young population with a mean age at
recruitment in the early 40s and a mean follow-up of 5 years. Therefore
the current age of participants is about 50 years. At this age, the
frequency and severity of aspirin complications is very low.2
Indeed the number of adverse events quoted in the paper's appendix is
only 21 in more than 400 aspirin-taking patients. Moreover, Rothwell and
colleagues3
have indicated that, for the general public or those at risk of more
common cancers, taking aspirin before 55 years of age will not have a
significant benefit. Furthermore, the mean period of treatment is just
more than 2 years and although this suggests an impressive effect, it
means that the long-term safety is unknown.4
In
conclusion, although this study is excellent news for patients with
Lynch syndrome, we need data from other large and long-term randomised
trials with cancer endpoints such as the AspECT trial to assess the
safety of aspirin in an older and more general population.5
paywalled - Preoperative diagnosis of metastatic ovarian cancer is related to origin of primary tumor - Guerriero - 2012 - Ultrasound in Obstetrics & Gynecology - Wiley Online Library
Preoperative diagnosis of metastatic ovarian cancer is related to origin of primary tumor - Guerriero - 2012 - Ultrasound in Obstetrics & Gynecology
Abstract
Objective
To
describe the gray-scale and color Doppler ultrasound features as well
as some clinical and biochemical features of metastatic ovarian tumors
according to the origin of the primary tumor in a large study
population,
Methods
This
was a retrospective analysis of 116 masses in 92 patients (mean age, 51
years) evaluated and treated at three European university centers for a
metastatic tumor in the ovary. All patients had undergone transvaginal
color Doppler ultrasound according to a standardized protocol prior to
surgery and tumor removal. Ultrasound features analyzed were
bilaterality, tumor volume, morphologic gray-scale appearance and color
score. CA 125 was also recorded.
Results
Primary tumor histological diagnosis was as follows: colon-sigmoid (n = 32), stomach (n = 28), breast (n = 20), uterus (n = 17), lymphoma (n = 4), liver-pancreas-biliary tract (n = 4) and miscellaneous (n
= 11). There were no differences in age, menopausal status or CA 125
values according to origin of primary tumor. Bilaterality was
significantly more frequent in stomach metastases (56%) in comparison
with colon-sigmoid and liver-pancreas-biliary tract metastases (18.5%
and 0%, respectively, P < 0.05). Median tumor volume was significantly lower in breast metastases (33.5 mL) compared with other metastases (P
< 0.05) except stomach metastases and metastatic tumors from the
miscellaneous group. Ovarian metastases from breast cancers were
significantly more frequently solid in comparison to stomach, colorectal
and uterine cancer metastases (95.0% vs. 60.8%, 46.8% and 70.6%,
respectively, P < 0.05), and tended to appear moderately or
highly vascularized. There were no differences in color score among all
groups, although the percentage of masses with abundant color was high
(50–82%).
Conclusions
Ovarian metastases derived from breast cancers tend to be small, solid and vascularized; they seem to be the only ovarian metastases whose primary tumor origin can be suspected by ultrasonography preoperatively. Color score does not seem to help suspect the origin of the primary tumor.Saturday, April 28, 2012
Medscape: Providers to Test Power of Apology in Malpractice Claims
Blogger's Note: of particular interest to PAHO/patient safety communities/risk management
Providers to Test Power of Apology in Malpractice Claims
Rivkin Center (Seattle) awards grant for cognitive study (ovarian cancer/chemobrain)
Blogger's Note: many ovarian cancer survivors who have gone before us would be happy with this news (Shirley Inveen, Sheryl Eisenbarth.....)
Rivkin Center awards grant for cognitive study:
CONGRATULATIONS DR. GRAY!
Heidi Gray, MD
University of Washington
Behavioral and neural indices of cognitive rehabilitation in ovarian cancer
Millions of ovarian cancer survivors live with residual symptoms of impaired thinking and impaired memory severe enough to interfere with basic activities of daily living and work. However, very little is known about how to treat problems in cognition. Pharmacologic interventions have only been modestly helpful, if at all, and not all patients desire or are able to take medications. Dr. Gray will examine the ability of a 7-week cognitive rehabilitation intervention to improve memory and thinking abilities in ovarian cancer survivors. In addition, the project will measure changes in brain activity patterns from the treatment using neuroimaging.
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|
press release: Moffitt Cancer Center researchers: Quality of life as important as quantity of life
Moffitt Cancer Center researchers: Quality of life as important as quantity of life
"The question of how well people are surviving cancer is as important as how long they survive cancer," .....
Prolonged fatigue after treatment
In a recent study published in Cancer, researchers from Moffitt found that when patients treated with chemotherapy or chemotherapy and radiation for breast cancer were compared to a control group who had not had cancer, the patients who had experienced chemotherapy and/or radiotherapy had more fatigue. These patients also had fatigue that lasted years after their therapy.
"This finding was contrary to our expectations," Jacobsen said. "Conventional thinking is that patients receiving chemotherapy would, over time, experience less fatigue and would eventually see their fatigue diminish to the levels of controls who had not had cancer, or to the level of fatigue they had prior to their chemotherapy.".......
Reply to W.R. Robinson from Chi: re: “Is the Easier Way Ever the Better Way? (ovarian cancer/neoadjuvant therapy/surgery/references...)
Blogger's Note: follows to prior posting/correspondence/dialogue; worthwhile reading this discussion/debate, note the common denominator in references
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
Reply to W.R. Robinson
Reply to W.R. Robinson
- Corresponding author: Dennis S. Chi, MD, Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; e-mail: gynbreast@mskcc.org.
+ Author Affiliations
We thank Robinson1 for his comments on our editorial, “Is the Easier Way Ever the Better Way?”2
Robinson disagreed with our article on two points. First, he stated
that it is “both disingenuous and unrealistic to… suggest
that fellowship-trained, Board-certified gynecologic
oncologists are not capable of operating on women with advanced ovarian
cancer.” Robinson also expressed concern that we were
suggesting that neoadjuvant chemotherapy (NACT) “somehow represents
a failure on the part of the physicians who are taking
‘the easy way out.'”
To the first point, we did not say that
fellowship-trained, Board-certified gynecologic oncologists are not
capable of operating
on women with advanced ovarian cancer. Rather, we
wanted to highlight that the number of patients who receive suboptimal
debulking
could be reduced by collaboration with other surgical
colleagues. Many gynecologic oncologists partner with urologists for
complex continent urinary conduits after pelvic
exenteration and with plastic surgeons for a myocutaneous flap after
radical
pelvic surgery, for example, and we believe that
patients with ovarian cancer should also be offered the potential
benefit
of subspecialty surgical consultation if it will
improve their overall survival. The complexity of preplanning surgical
consultations
for advanced ovarian cancer debulking surgery should
not be any different than for these other surgical collaborations.
It is incumbent on the gynecologic oncologist to ensure that pressures to minimize operating room and intensive care unit
usage do not compromise the surgical outcome for our patients.........
The author(s) indicated no potential conflicts of interest.
Friday, April 27, 2012
Correspondence: Neoadjuvant Chemotherapy (ovarian cancer) Is Rarely the Easy Way Out + references +discussion on gyn specialists/general surgeons
Blogger's Note: worthwhile reading/pondering...
~~~~~~~~~~~~~
Neoadjuvant Chemotherapy Is Rarely the Easy Way Out
To the Editor:
I appreciate the thoughtful analysis by Chi et al1 in the November 1 issue of Journal of Clinical Oncology,
in the article entitled, “Is the Easier Way Ever the Better Way?” Chi
et al make a very literate argument against using
neoadjuvant chemotherapy (NACT) for ovarian cancer,
continuing a discussion that has lingered among oncologists for more
than
25 years. The argument has heated up recently as a
result of several prospective studies, particularly that of Vergote et
al,2 which showed no difference in survival in patients treated with either primary surgery or NACT.
I must, however, disagree with Chi et al1
on two points. The first of these is the suggestion by the authors that
patients with stage IIIC/IV ovarian cancer should
routinely be referred to ultraspecialist centers
that are capable of performing advanced upper abdominal surgery. In
reality,
the great majority of patients with ovarian cancer
in the United States have been and will be treated in community settings
for the foreseeable future. The professional
societies that represent gynecologic oncology have for years strongly
recommended
that ovarian cancer be handled by
fellowship-trained gynecologic oncologists. This effort has met with
mixed success; in many
communities it is still the norm for women with
advanced ovarian cancer to be operated on by physicians with no special
oncologic
surgical training.......plus references:
paywalled: Data for cancer comparative effectiveness research - Meyer - 2012 - Cancer - Wiley Online Library
Data for cancer comparative effectiveness research
Abstract
Comparative effectiveness research (CER) can efficiently and rapidly generate new scientific evidence and address knowledge gaps, reduce clinical uncertainty, and guide health care choices. Much of the potential in CER is driven by the application of novel methods to analyze existing data. Despite its potential, several challenges must be identified and overcome so that CER may be improved, accelerated, and expeditiously implemented into the broad spectrum of cancer care and clinical practice. To identify and characterize the challenges to cancer CER, the authors reviewed the literature and conducted semistructured interviews with 41 cancer CER researchers at the Agency for Healthcare Research and Quality's Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) Cancer CER Consortium. Several data sets for cancer CER were identified and differentiated into an ontology of 8 categories and were characterized in terms of strengths, weaknesses, and utility. Several themes emerged during the development of this ontology and discussions with CER researchers. Dominant among them was accelerating cancer CER and promoting the acceptance of findings, which will necessitate transcending disciplinary silos to incorporate diverse perspectives and expertise. Multidisciplinary collaboration is required, including those with expertise in nonexperimental data, statistics, outcomes research, clinical trials, epidemiology, generalist and specialty medicine, survivorship, informatics, data, and methods, among others.Recommendations highlight the systematic, collaborative identification of critical measures; application of more rigorous study design and sampling methods; policy-level resolution of issues in data ownership, governance, access, and cost; and development and application of consistent standards for data security, privacy, and confidentiality.
paywalled: Developing a useful, user-friendly website for cancer patient follow-up: users' perspectives on ease of access and usefulness - European Journal of Cancer Care
Developing a useful, user-friendly website for cancer patient follow-up: users' perspectives on ease of access and usefulness - European Journal of Cancer Care
Developing a useful, user-friendly website for cancer patient follow-up: users' perspectives on ease of access and usefulness
UK
cancer survival has improved, leading to an increase in review patients
and pressure on clinics...... Acceptability: Final
evaluation (n= 103) was positive although many would like to
maintain face-to-face hospital contact. User involvement in website
design can ensure patient needs are met. A website model for follow-up
will suit some patients but others will prefer clinical contact.
paywalled: First-line treatment of advanced ovarian cancer with paclitaxel/carboplatin with or without epirubicin (TEC versus TC)—a gynecologic cancer intergroup study of the NSGO, EORTC GCG and NCIC CTG
Epirubicin (Brand name: Ellence)
~~~~~~~~~~~~~~~~~~~~~
First-line treatment of advanced ovarian cancer with paclitaxel/carboplatin with or without epirubicin (TEC versus TC)—a gynecologic cancer intergroup study of the NSGO, EORTC GCG and NCIC CTG
Background: The addition of anthracyclines to platinum-based chemotherapy may provide benefit in survival in ovarian cancer patients. We evaluated the effect on survival of adding epirubicin to standard carboplatin and paclitaxel.
Conclusion: The addition of epirubicin to standard carboplatin and paclitaxel treatment did not improve survival in patients with advanced ovarian, tubal or peritoneal cancer.
Thursday, April 26, 2012
paywalled: Coffee intake and breast cancer risk in the NIH-AARP diet and health study cohort - Gierach - 2011 - International Journal of Cancer - Wiley Online Library
Coffee intake and breast cancer risk in the NIH-AARP diet and health study cohort - International Journal of Cancer
"These findings from a large prospective cohort do not support a role of coffee intake in breast carcinogenesis."
UK: Advanced Solid Tumours Clinical Trial: Phase I Study of AT13148, a Novel AGC Kinase Inhibitor [Conditions: Advanced Solid Tumours; Interventions: AT13148]
Advanced Solid Tumours Clinical Trial: Phase I Study of AT13148, a Novel AGC Kinase Inhibitor [Conditions: Advanced Solid Tumours; Interventions: AT13148]
The purpose of this first clinical study of the noval
multiple AGC kinase inhibitor, AT13148, is to identify the recommended
dose for future studies in cancer patients by exploring the safety and
maximum tolerated dose and biological effects in patients with advanced
solid tumours...
Brief Summary
Official Title: “A Cancer
Research UK Phase I First in Man Study of the Novel AGC Kinase Inhibitor
AT13148 Given Orally in Patients With Advanced Solid Tumours.”
The purpose of this first clinical study of the noval multiple
AGC kinase inhibitor, AT13148, is to identify the recommended dose for
future studies in cancer patients by exploring the safety and maximum
tolerated dose and biological effects in patients with advanced solid
tumours.
- Study Type: Interventional
- Study Design: Masking: Open Label, Primary Purpose: Treatment
- Study Primary Completion Date: October 2015
Detailed Clinical Trial Description
AT13148 is a new drug which looks promising in laboratory
studies. We now wish to find out if it will be useful in treating
patients with cancer. AT13148 is a type of drug called a protein kinase
inhibitor. It blocks several different chemical messengers (enzymes)
called AGC kinase proteins. These chemical messengers are part of the
signaling process within cells which can make cells produce chemicals
that trigger and control cell growth and cell death. In some types of
cancer these chemical messengers are 'switched on' or 'switched off'
permanently due to changes in the genes of cells called "gene mutations"
leading to uncontrolled cancer cell growth. AT13148 targets multiple
protein kinases from three families of kinases unlike many of the other
protein kinase inhibitors currently being tested which target just one
or two kinases. This may mean that it will work better and in a wider
group of cancer patients. Patients will not be selected to take part
based on having these gene mutations for this first trial because we
want to learn more about which mutations are most important but this
would be the hope for future trials. The patient population anticipated
to benefit from this drug includes certain types of breast, prostate and
ovarian cancer which more commonly have these gene mutations.
26 APR 2012 - Nutrition and physical activity guidelines for cancer survivors - CA: A Cancer Journal for Clinicians - Wiley Online Library
Nutrition and physical activity guidelines for cancer survivors - CA: A Cancer Journal for Clinicians
".... After receiving a diagnosis of cancer, survivors soon find there are few clear answers to even the simplest questions, such as: Should I change what I eat? Should I exercise more? Should I gain or lose weight? Should I take dietary supplements? Cancer survivors receive a wide range of advice from many sources about foods they should eat, foods they should avoid, how they should exercise, and what types of supplements they should take, if any. Unfortunately, this advice is often inconsistent and not supported by data...."
Ovarian Cancer
Ovarian cancer is the leading cause of death from gynecologic malignancies in the United States.4
Symptoms tend be nonspecific, making early detection difficult.
Consequently, most ovarian cancers are diagnosed at an advanced stage
when the prognosis is poor, with an overall 10-year survival rate of
39%.4 The role of lifestyle factors in ovarian cancer prognosis is largely unknown.138, 242 To our knowledge, only 3 studies139, 140, 243
have evaluated the role of dietary factors in ovarian cancer survival.
These 3 studies were based on prospective follow-up of the cases
participating in case-control studies and evaluated the association
between prediagnosis dietary intake and mortality outcomes. One study,
conducted in China, focused on the role of green tea and reported that a
higher frequency and quantity of green tea intake after diagnosis was
associated with better survival.243 The other 2 studies, conducted in Australia140 and the United States,139
suggested that prediagnosis dietary intake may influence the survival
experience of patients with ovarian cancer. Both studies tended to
support the association of fruit and vegetable consumption with better
survival. Dairy food intake was associated with poorer survival in one
of the studies,140 while in the other, only milk consumption and not total dairy food consumption was inversely associated with survival.139 Meat consumption was associated with better survival in the Australian study,140 and with lower survival in the study conducted in the United States.139
While these studies controlled for most relevant covariates, they did
not include treatment information. In addition, these studies did not
evaluate dietary intake after diagnosis. However, they do suggest that
dietary intake may influence ovarian cancer survival and warrant further
research in this area.
Only one study,
also following cases in a case-control study for mortality, has
evaluated the role of physical activity in ovarian cancer survival.244
Prediagnosis physical activity was ascertained as hours per week for 3
life periods (childhood, between ages 18-30 years, and in recent years).
The study also evaluated the role of changes in physical activity over
time. There was not much indication of an association with survival for
any of these variables, except for physical activity at aged 18 to 30
years, which seemed to be associated with better survival for women with
early stage ovarian cancer and with worse survival for women with an
advanced stage of disease at diagnosis.245
The
relationship between excess weight and ovarian cancer survival has been
evaluated by relatively few studies. Obesity may affect ovarian cancer
survival by having a negative impact on optimal surgical and cytotoxic
treatment and increasing the likelihood of postoperative complications.246 Overall, the literature evaluating the association between weight/BMI and ovarian cancer survival is limited and inconclusive.76, 242
Cohort studies evaluating the role of prediagnosis obesity obtained at
baseline on ovarian cancer mortality have generally found elevated
ovarian cancer mortality among obese women.234, 247
Other studies evaluating the role of prediagnosis BMI on ovarian cancer
survival by following cases in a case-control study or clinical trial
(using baseline data) have offered conflicting results.242
The role of postdiagnosis body size and weight changes on ovarian
cancer survival is largely unknown. Only one study has reported on
weight changes during chemotherapy and ovarian cancer survival and found
that, among patients with advanced ovarian cancer, weight loss during
chemotherapy was associated with worse prognosis; however, it is
difficult to determine whether this weight loss was involuntary or
intentional.248
In
summary, while the current evidence is limited and inconclusive, it
points to a possible role of dietary factors, physical activity, and
body size and weight changes in modulating ovarian cancer survival, and
for physical activity in improving the quality of life among ovarian
cancer survivors. Further studies are needed before public health
recommendations can be made.
paywalled: Coffee and tea consumption and the risk of ovarian cancer: a prospective cohort study and updated meta-analysis
Blogger's Note/Opinion: as per abstract, to date and studies over decades, have not found a link between coffee/tea/ovarian cancer risk - so, the question is this: how many more studies will it take to finally put this issue to rest? Unless there are novel (new) findings then we need to move forward.
Coffee and tea consumption and the risk of ovarian cancer: a prospective cohort study and updated meta-analysis
Abstract
Background: In 2007 the World Cancer Research Fund Report concluded that there was limited and inconsistent evidence for an effect of
coffee and tea consumption on the risk of epithelial ovarian cancer (EOC).
Objective: In the European Prospective Investigation into Cancer and Nutrition (EPIC), we aimed to investigate whether coffee intakes,
tea intakes, or both are associated with the risk of EOC.
Design: All women participating in the EPIC (n
= 330,849) were included in this study. Data on coffee and tea
consumption were collected through validated food-frequency
questionnaires at baseline. HRs and 95% CIs were
estimated by using Cox proportional hazards models. Furthermore, we
performed
an updated meta-analysis of all previous
prospective studies until April 2011 by comparing the highest and lowest
coffee-
and tea-consumption categories as well as by using
dose-response random-effects meta-regression analyses.
Results: During a median
follow-up of 11.7 y, 1244 women developed EOC. No association was
observed between the risk of EOC and coffee
consumption [HR: 1.05 (95% CI: 0.75, 1.46) for the
top quintile compared with no intake] or tea consumption [HR: 1.07 (95%
CI: 0.78, 1.45) for the top quintile compared with
no intake]. This lack of association between coffee and tea intake and
EOC risk was confirmed by the results of our
meta-analysis.
Conclusion: Epidemiologic studies do not provide sufficient evidence to support an association between coffee and tea consumption and
risk of ovarian cancer.
paywalled: Systematic review of progesterone use by midlife and menopausal women
Systematic review of progesterone use by midlife and menopausal women: Publication year: 2012
Source: Maturitas
Progesterone treatment for menopausal symptoms is still controversial. Progesterone levels fall during menopause transition, therefore some menopausal women may benefit from progesterone therapy. A systematic review was conducted of studies published from 2001 reporting on progesterone use to treat symptoms associated with menopause or postmenopausal women. Fourteen data bases were searched using the search terms progesterone, menopause, aged, female and human; exclusions were breast cancer, animal and contraception. Thirteen studies were selected for inclusion (11 clinical trials, 1 cohort study and 1 qualitative study), evaluating progesterone effects on menopausal symptoms, bone, sleep, skin, cognition, plasma lipids and plaque progression. Most studies were of low methodological quality (GRADE low or very low). Progesterone improved vasomotor symptoms and sleep quality, with minimal risk. Large studies designed to identify confounders, such as hormone levels, menopausal status and metabolism are required to understand the place of progesterone in clinical practice.
Seth's Blog: Don't expect applause
Don't expect applause:
Accept applause, sure, please do.
But when you expect applause, when you do your work in order (and because of) applause, you have sold yourself short. That's because your work is depending on something out of your control. You have given away part of your art. If your work is filled with the hope and longing for applause, it's no longer your work--the dependence on approval has corrupted it, turned it into a process where you are striving for ever more approval.
Who decides if your work is good? When you are at your best, you do. If the work doesn't deliver on its purpose, if the pot you made leaks or the hammer you forged breaks, then you should learn to make a better one. But we don't blame the nail for breaking the hammer or the water for leaking from the pot. They are part of the system, just as the market embracing your product is part of marketing.
"Here, here it is, it's finished."
If it's finished, the applause, the thanks, the gratitude are something else. Something extra and not part of what you created. To play a beautiful song for two people or a thousand is the same song, and the amount of thanks you receive isn't part of that song.
But when you expect applause, when you do your work in order (and because of) applause, you have sold yourself short. That's because your work is depending on something out of your control. You have given away part of your art. If your work is filled with the hope and longing for applause, it's no longer your work--the dependence on approval has corrupted it, turned it into a process where you are striving for ever more approval.
Who decides if your work is good? When you are at your best, you do. If the work doesn't deliver on its purpose, if the pot you made leaks or the hammer you forged breaks, then you should learn to make a better one. But we don't blame the nail for breaking the hammer or the water for leaking from the pot. They are part of the system, just as the market embracing your product is part of marketing.
"Here, here it is, it's finished."
If it's finished, the applause, the thanks, the gratitude are something else. Something extra and not part of what you created. To play a beautiful song for two people or a thousand is the same song, and the amount of thanks you receive isn't part of that song.
medical news: Study confirms overuse of blood transfusions during surgery
Study confirms overuse of blood transfusions during surgery
"Citing the lack of clear guidelines for ordering blood transfusions during surgery, Johns Hopkins researchers say a new study confirms there is still wide variation in the use of transfusions and frequent use of transfused blood in patients who don't need it.
The resulting overuse of blood is problematic, the researchers say, because blood is a scarce and expensive resource and because recent studies have shown that surgical patients do no better, and may do worse, if given transfusions prematurely or unnecessarily. "Transfusion is not as safe as people think," says Steven M. Frank, M.D., leader of the study described in the journal Anesthesiology.....
Correspondence: Bevacizumab in Neoadjuvant Treatment for Breast Cancer — NEJM
Blogger's Note: correspondence/author's reply/references; while this is specific to Avastin/breast cancer, future trial protocols may take note
Bevacizumab in Neoadjuvant Treatment for Breast Cancer — NEJM
PLoS ONE: Effect of Angiogenesis Inhibitor (Avastin) Bevacizumab on Survival in Patients with Cancer: A Meta-Analysis of the Published Literature
Blogger's Note: indicates which cancer patients did/did not show PFS/OS; limited to combo therapies (lack of monotherapy trials); read limitations to the analysis (eg. individual patient data/meta-analysis...); notes serious side effects
PLoS ONE: Effect of Angiogenesis Inhibitor Bevacizumab on Survival in Patients with Cancer: A Meta-Analysis of the Published Literature
paywalled: Role of HE4, CA72.4, and CA125 in monitoring ovarian cancer.
Role of HE4, CA72.4, and CA125 in monitoring ovarian cancer.
Abstract
The aim of this study was to investigate the role of biomarkers CA125, HE4, and CA72.4 at diagnosis and throughout the follow-up in patients with epithelial ovarian cancer (EOC). Thirty-nine patients with EOC were deemed eligible, and 20 were followed up. CA125, HE4, and CA72.4 serum levels were determined for all patients at initial diagnosis of EOC. Among these patients, the number of cases with an elevated level of each individual marker was CA125 77 %, HE4 85 %, and CA72.4 72 %. A statistically significant difference was observed between the level of HE4 when compared to CA72.4 (p < 0.02). In the follow-up phase, we observed tumor marker levels fluctuating according to response to chemotherapy. When combining two out of the three biomarkers together, we observed increased values of CA125 and CA72.4 in 55 % of the patients, increased values of CA125 and HE4 in 65 % of the patients, and finally increased HE4 and CA72.4 in 75 % of the patients. A statistically significant difference was observed when combining HE4 and CA72.4, but not CA125 and CA 72.4 (p < 0.002). In conclusion, our study demonstrates that the association of three biomarkers CA125, HE4, and CA72.4 provides a valuable contribution in the follow-up of EOC patients.open access: Cancer, Fertility Preservation, and Future Pregnancy: A Comprehensive Review
Cancer, Fertility Preservation, and Future Pregnancy: A Comprehensive Review
Obstetrics and Gynecology International
Volume 2012 (2012), Article ID 953937, 11 pages
doi:10.1155/2012/953937 Review Article Cancer, Fertility Preservation, and Future Pregnancy: A Comprehensive Review
- Abstract
- Introduction
- Methods and Materials
- Results and Discussion
- Options for Fertility Preservation
- Additional Considerations
- Pregnancy after Cancer
Conclusions
Given the relatively high incidence of cancer in reproductive age women and improvements in 5-year survival, an increasing number of women are presenting for discussion of fertility preservation and pregnancy after cancer treatment. The ASCO published recommendations in 2006 on fertility preservation in cancer patients. These guidelines state that oncologists should address the possibility of infertility with cancer patients and be prepared to discuss possible fertility preservation options or refer the patient to a reproductive specialist. Part of the difficulty in counseling patients regarding the risk of infertility and/or subsequent pregnancy complications is that the risks are dependent on several factors. These risks include the dose and duration of treatment, other risk factors for infertility, the age of the patient, and the patient’s baseline ovarian reserve at the time of initiation of treatment.
paywalled: Predisposition gene identification in common cancers by exome sequencing: insights from familial breast cancer.
Breast Cancer Res Treat. 2012 Apr 18;
Abstract
The genetic component of breast cancer predisposition remains largely unexplained. Candidate gene case-control resequencing has identified predisposition genes characterised by rare, protein truncating mutations that confer moderate risks of disease. In theory, exome sequencing should yield additional genes of this class. Here, we explore the feasibility and design considerations of this approach. We performed exome sequencing in 50 individuals with familial breast cancer, applying frequency and protein function filters to identify variants most likely to be pathogenic. We identified 867,378 variants that passed the call quality filters of which 1,296 variants passed the frequency and protein truncation filters. The median number of validated, rare, protein truncating variants was 10 in individuals with, and without, mutations in known genes. The functional candidacy of mutated genes was similar in both groups. Without prior knowledge, the known genes would not have been recognisable as breast cancer predisposition genes. Everyone carries multiple rare mutations that are plausibly related to disease. Exome sequencing in common conditions will therefore require intelligent sample and variant prioritisation strategies in large case-control studies to deliver robust genetic evidence of disease association.
paywalled: Breast-feeding and risk of epithelial ovarian cancer (clear cell/endometrioid)
Breast-feeding and risk of epithelial ovarian cancer
AbstractPURPOSE:
Evidence suggests that breast-feeding may decrease the risk of epithelial ovarian cancer but it is not clear whether there is a relationship with duration of breast-feeding, patterns of breast-feeding, or particular histological subtypes of ovarian cancer. We sought to investigate these issues in detail.METHODS:
Data from participants in a population-based study of ovarian cancer in western Washington State, USA (2002-2007) who had had at least one birth (881 cases and 1,345 controls) were used to assess relations between patterns of breast-feeding and ovarian cancer. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI).RESULTS:
Women who ever breast-fed had a 22 % reduction in risk of ovarian cancer compared with those who never breast-fed (OR = 0.78, 95% CI 0.64-0.96) and risk reduction appeared greater with longer durations of feeding per child breast-fed (OR = 0.56, 95% CI 0.32-0.98 for 18 months average duration breast-feeding versus none). Introduction of supplementary feeds did not substantially alter these effects. The overall risk reduction appeared greatest for the endometrioid and clear cell subtypes (OR per month of average breast-feeding per child breast-fed = 0.944, 95% CI 0.903-0.987).CONCLUSIONS:
Among women who have had the opportunity to breast-feed, ever breast-feeding and increasing durations of episodes of breast-feeding for each breast-fed child are associated with a decrease in the risk of ovarian cancer independent of numbers of births, which may be strongest for the endometrioid subtype.paywalled: Journal of Cancer Education: Knowledge of Reproductive System Cancers, Their Treatments and Side Effects (Canada)
Knowledge of Reproductive System Cancers, Their Treatments and Side Effects
Abstract
We
explored, via an online questionnaire, knowledge of breast and
reproductive system cancers in patients and non-patients
who access the internet for information on these diseases.
We compared that knowledge to the attention the diseases have received
in medical research and on the Internet. Data were collected
from 690 respondents (37 % male, 63 % female) about their knowledge
of prevalence, lethality, treatments and side effects of
testicular, prostate, breast, uterine, cervical and ovarian cancers.
Most males, but only half of the female participants, were
patients themselves. Although participants showed better knowledge
of cancers specific to their own sex, both sexes felt
familiar with breast cancer and less aware of other cancers. Women were
as aware as men of side effects of treatments for male
reproductive cancers. Sex differences in awareness appear to reflect
different attitudes towards illness, bias toward females as
caregivers, and the disproportionate media attention given to
breast cancer.
Wednesday, April 25, 2012
open access: Cell–cell and cell–matrix dynamics in intraperitoneal cancer metastasis (ovarian/GI tract cancers)
Cell–cell and cell–matrix dynamics in intraperitonealcancer metastasis
Abstract/pdf full text:
IntroductionIntraperitoneal dissemination is the primary metastatic route
of ovarian cancers. It is also a common progression for
gastrointestinal malignancies including colorectal, gastric,
and pancreatic cancers.....
~~~~~~~~~~~~~~~~~
The peritoneal metastatic route of cancer dissemination
is shared by cancers of the ovary and gastrointestinal
tract. Once initiated, peritoneal metastasis typically proceeds
rapidly in a feed-forward manner. Several factors
contribute to this efficient progression. In peritoneal metastasis,
cancer cells exfoliate into the peritoneal fluid and
spread locally, transported by peritoneal fluid. Inflammatory
cytokines released by tumor and immune cells compromise
the protective, anti-adhesive mesothelial cell layer that lines
the peritoneal cavity, exposing the underlying extracellular
matrix to which cancer cells readily attach. The peritoneum
is further rendered receptive to metastatic implantation and
growth by myofibroblastic cell behaviors also stimulated by
inflammatory cytokines. Individual cancer cells suspended
in peritoneal fluid can aggregate to form multicellular spheroids.
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