Plasma miRNAs as Diagnostic and Prognostic Biomarkers for Ovarian Cancer

open access (technical)

"Carbohydrate antigen-125 (CA-125) is the most frequently used biomarker for ovarian cancer detection [4], but it is only elevated in approximately 50% of stage I EOCs and 70%–90% of advanced cases [5]. Hence, there is a critical need for novel biomarkers that are more sensitive and specific for detecting EOC when used alone or in combination with CA-125. Recently, microRNAs (miRNAs), a family of small regulatory RNAs, emerged as possible plasma markers for human disease, including cancer, because of their relative stability in the circulation [6]."

Background

Most (70%) epithelial ovarian cancers (EOCs) are diagnosed late. Non-invasive biomarkers that facilitate disease detection and predict outcome are needed. The microRNAs (miRNAs) represent a new class of biomarkers. This study was to identify and validate plasma miRNAs as biomarkers in EOC.

Methodology/Principal Findings

We evaluated plasma samples of 360 EOC patients and 200 healthy controls from two institutions.

Conclusions/Significance

Our findings indicate that plasma miR-205 and let-7f are biomarkers for ovarian cancer detection that complement CA-125; let-7f may be predictive of ovarian cancer prognosis.


 

Chemo Brain: A Decade of Evidence - Chemo Brain May Become Increasingly Common

A Decade of Evidence

Editor's Note: Cognitive dysfunction is a recognized entity that can occur in cancer patients treated with chemotherapy or radiotherapy. Medscape Oncology spoke with Jeffrey S. Wefel, PhD, Section Chief of Neuropsychology at MD Anderson Cancer Center, Houston, Texas, for an overview of what the evidence shows about the condition popularly known as "chemo brain.".....

• 3 Lines of Evidence Converge
• Chemotherapy Not the Sole Culprit
• Duration of Dysfunction Unknown
• Efforts to Determine Risk for Dysfunction
• Research Into Preventive Strategies

• References

 
 

Mind the Gap, NIH Seminar Series - Bridging the Gap Between Evidence and Practice

Mind the Gap

Bridging the Gap Between
Evidence and Practice

Medicine: Mind the Gap is a lecture series that explores issues at the intersection of research, evidence, and clinical practice—areas in which conventional wisdom may be contradicted by recent evidence. From the role of advocacy organizations in medical research and policy, to off-label drug use, to the effectiveness of continuing medical education, the seminar series will aim to engage the National Institutes of Health community in thought-provoking discussions to challenge what we think we know and to think critically about our role in today’s research environment.
 

Ontario Tumour Bank to supply samples to COEUR, a pan-Canadian ovarian cancer research project

press release

TORONTO, Nov. 1, 2013 /CNW/ - The Ontario Tumour Bank (OTB) will supply ovarian tumour samples to the Canadian Ovarian Cancer Experimental Unified Resource (COEUR) in an effort to further enhance ovarian cancer research in Canada, announced Dr. John Bartlett, Provincial Principal Investigator, OTB and Director of the Ontario Institute for Cancer Research's (OICR) Transformative Pathology Program.
"We are thrilled to be contributing these samples to COEUR and to be a part of such an innovative and exciting initiative to discover more about the causes of ovarian cancer and the best avenues for treatment," said Dr. Bartlett. "Through sharing and collaboration we are more likely to identify the best individualized treatment strategies to improve outcomes for patients with ovarian cancer."
The COEUR initiative, a project of the Terry Fox Research Institute, will establish a collection of ovarian cancer samples and clinical data from 2,000 women. Researchers will be provided with controlled access to the resources so they can perform biomarker studies with a particular focus on predicting response to therapy......

Letter: Renal risk stratification with the new oral anticoagulants (JULY 2013)

open access

"...Originally, the US Food and Drug Administration approved dabigatran (Pradaxa) at a dose of 150 mg orally twice daily in patients with a creatinine clearance of 15 to 30 mL/min/1.73 m². This dosing corresponded to the estimated glomerular filtration rate (eGFR) in patients with stage 4 chronic kidney disease, but this dosing is contraindicated in other guidelines worldwide (Canada, Europe, the United Kingdom, Japan, Australia, and New Zealand).² Not unexpectedly, 3,781 serious adverse effects were noted in the 2011 US postmarketing experience with dabigatran. These included death (542 cases), hemorrhage (2,367 cases), acute renal failure (291 cases), stroke (644 cases), and suspected liver failure (15 cases).³ Thirteen months after dabigatran’s approval in the United States, Boehringer Ingelheim changed the dosage and product guidelines.^2–4 The new dosage⁴ is 75 mg twice daily for patients with a creatinine clearance of 15 to 30 mL/min/1.73 m².

Therefore, I suggest a nephrologic “way out”⁵ when using the new oral anticoagulants to avoid the problems with dabigatran noted above......

 

Sleep disturbances in cancer patients: Underrecognized and undertreated

open access

"Depending on the methods used and populations studied, at least 30% and perhaps more than half of patients with cancer have insomnia (TABLE 1).^3,4,8–14 It is one of the most commonly reported complaints in this group,^15–17 and it occurs before, during, and after treatment of cancer."

Key points

Sleep disturbances, primarily insomnia, profoundly affect all aspects of quality of life.

Insomnia can be caused or worsened by a number of other conditions, such as pain, fatigue, depression, and anxiety, and these in turn can be worsened by insomnia. 

Cognitive-behavioral therapy is the treatment of choice for chronic insomnia. Underlying problems should be addressed.

Drugs are often prescribed to help cancer patients sleep but should be used with caution, as there is limited information from clinical trials in this population. 

~~~~~~~~~~~~~

Many cancer patients don’t sleep well, for a variety of reasons. It is an important problem: not only does poor sleep worsen quality of life, it may affect prognosis. Moreover, treatment is available.

Yet many physicians caring for cancer patients do not ask about sleep problems, underestimating their impact or focusing on more urgent problems. Also, patients may not want to bring up the topic because they consider poor sleep to be unavoidable and untreatable and because they fear that reporting it may shift the focus of their treatment from trying to cure the cancer to easing its symptoms.

This practical review will help health care professionals avoid the common barriers to diagnosis and treatment of poor sleep in cancer patients. Because there are few data on other sleep disorders such as sleep apnea and restless leg syndrome, we will focus on the most common one in cancer patients—insomnia—and its effects on other symptoms and quality of life....

 

The effects of metformin on ovarian cancer

Blogger's Note: Metformin is a common drug used in diabetic patients

abstract

OBJECTIVE:

The potential therapeutic effects of metformin on several cancers were reported. However, the evidence of the effects of metformin on ovarian cancer is still limited and inconclusive. This systematic review and meta-analysis study aim to summarize the existing evidence of the therapeutic effects of metformin on ovarian cancer.

METHODS:

We performed systematic searches using electronic databases including PubMed and EMBASE until December 2012. Key words included "metformin" AND ("ovarian cancer" OR "ovary tumor"). All human studies assessing the effects of metformin on ovarian cancer were eligible for inclusion. All articles were reviewed independently by 2 authors with a standardized approach for the purpose of study, study design, patient characteristics, exposure, and outcomes. The data were pooled using a random-effects model.

RESULTS:

Of 190 studies retrieved, only 3 observational studies and 1 report of 2 randomized controlled trials were included. Among those studies, 2 reported the effects of metformin on survival outcomes of ovarian cancer, whereas the other 2 reported the effects of metformin on ovarian cancer prevention. The findings of studies reporting the effects on survival outcomes indicated that metformin may prolong overall, disease-specific, and progression-free survival in ovarian cancer patients. The results of studies reporting the effects of metformin on ovarian cancer prevention were meta-analyzed. It indicated that metformin tended to decrease occurrence of ovarian cancer among diabetic patients with the pooled odds ratio of 0.57 (95% confidence interval, 0.16-1.99).

CONCLUSIONS:

Our findings showed the potential therapeutic effects of metformin on survival outcomes of ovarian cancer and ovarian cancer prevention. However, most of the evidence was observational studies. There is a call for further well-conducted controlled clinical trials to confirm the effects of metformin on ovarian cancer survival and ovarian cancer prevention.

 

Ovarian cancer: sites of recurrence

abstract

INTRODUCTION:

Improved knowledge of recurrence sites after contemporary surgical management of ovarian cancer is needed.

MATERIAL AND METHODS:

We retrospectively reviewed consecutive patients managed for epithelial ovarian or tubal cancer with surgery and platinum-based chemotherapy between January 1, 2005, and December 31, 2009, in a tertiary teaching hospital. The site of first recurrence was recorded. Univariate analysis was performed to identify factors associated with site-specific recurrence. Overall survival and progression-free survival were computed using the Kaplan-Meier method, and log-rank tests were performed to assess the impact on survival of the variables of interest.

RESULTS:

Recurrences were noted in 3 (20%) of 15 International Federation of Gynecologists and Obstetricians stage I to IIa patients and 36 (62.1%) of 58 International Federation of Gynecologists and Obstetricians IIb to IV patients, and the median progression-free survival was 21.6 (2.5-71) and 19.3 (1.8-67.6) months, respectively. In the advanced-disease group, 75% of recurrences involved the peritoneum and 40% were confined to the peritoneum; peritoneal recurrences developed at both treated and untreated sites. Peritoneal recurrence was associated with greater initial peritoneal involvement (Sugarbaker score, 12.1 ± 8.2 vs 7.1 ± 7.4; P = 0.01) and residual postoperative tumor. Nodal recurrences were noted in 38% of all recurrences, usually in combination with peritoneal recurrence and in the abdominal territories. Isolated distant metastasis was a rare mode of recurrence (8%).

CONCLUSIONS:

The peritoneum is the main recurrence site in both early and advanced ovarian cancer. Initial disease spread and extent of surgery are associated with the recurrence risk. This article supports the view that more attention should be directed toward extensive treatment of the peritoneum.

 

 

Editorial: Multimorbidity and cancer outcomes: a need for more research

open access

....In this issue of Clinical Epidemiology, comprehensive data on the impact of comorbidity and survival in cancer patients are reported. These provide very important insight into the association between multimorbidity and cancer prognoses.
These analyses underscore the need for comprehensive, well-designed observational research on comorbidity and cancer. Findings from such types of research can be translated into clinical practice through development, testing, and implementation of intervention strategies designed to minimize the impact of comorbidity and the complications of cancer and its treatment. Such research is urgently needed since many cancer patients with multimorbidity have not benefitted from the recent advances in cancer treatment.

Secular, Spiritual, and Religious Existential Concerns of Women with Ovarian Cancer during Final Diagnostics and Start of Treatment

open access

 Conclusions

To involve patient resources has become a mantra in health care, including within the context of cancer treatment and care. However, while this approach might sound obviously correct, implementing it in daily clinical practice has proven to be difficult.

Hope and courage to face life represent significant personal resources that are created not only in the interplay between body and mind but also between patients and their healthcare professionals. The overall finding that it was not simply the women’s physical bodies but rather their whole lives that became impacted by the disease and treatment highlighted the importance of maintaining a professional engagement and holistic approach from the beginning of treatment—in particular during highly specialised fast-track clinical regimes.

The women dealt with their hope dialectically so that hope and despair could be presented simultaneously. Experiencing personal comfort and strength can reinforce hope, and we find it fair to conclude that the patients’ inner resources thus can be activated and strengthened by adjusted information of the disease and its treatment, psychosocial support, and physical care right from the commencement of the treatment modalities.....


6. Implications for Clinical Practise

Based on the findings presented in this paper we suggest the following.

(i)That person-centred care is trained and implemented in oncology settings.
(ii)That healthcare professionals focus also on the general health and everyday lives of the patients during treatment.
(iii)That physical comfort and well-being are seen, not as excessive luxury but as important tools to sustain and strengthen hope and courage to face life during treatment.
(iv)That communication and cooperation during transitions are further developed and prioritized.
(v)That supportive followup and rehabilitation are offered as an integrated part of the treatment for patients in need of it.(
vi)That patients are given the opportunity to develop, share, and adjust their narratives of illness during their treatment trajectory. 

Comorbidity and survival of Danish ovarian cancer patients from 2000-2011: a population based cohort study

open access

Published:	01 November 2013

Objective: To examine the prevalence of comorbidity among patients diagnosed with epithelial ovarian cancer in the Central Denmark Region and to study the impact of comorbidity on cancer survival over time.

Methods: We included women recorded with a first-time diagnosis of epithelial ovarian cancer in the Danish National Registry of Patients in the Central Denmark region between 2000 and 2011. We followed their survival through the Danish Civil Registration System. We estimated 1- and 5-year survival overall and stratified by Charlson Comorbidity Index score. We used Cox proportional hazard regression analyses to compute adjusted mortality rate ratios (MRRs) within different calendar time periods overall and by comorbidity level.

Results: We identified 1,540 patients. In 2000–2002, 25% of the newly diagnosed ovarian cancer patients had a comorbidity diagnosis compared with 35% in 2009–2011. Median age increased from 61 to 66 years. One-year overall survival changed from 73% (95% confidence interval [CI]: 69–78) in 2000–2002 to 69% (95% CI: 63–73) in 2009–2011, corresponding to an age- and comorbidity-adjusted MRR of 1.03 (95% CI: 0.79–1.36). Five-year survival changed only slightly during the study period, from 37% (95% CI: 32–42) in 2000–2002 to 39% (95% CI: 34–44) in 2009–2011. In patients with Charlson score ≥3, 1-year survival changed from 63% (95% CI: 35–81) in 2000–2002 to 41% (95% CI: 24–57) in 2003–2005 and thereafter stabilized. One-year survival changed from 56% (95% CI: 44–66) to 64% (95% CI: 53–74) in patients with Charlson score 1–2. Compared with Charlson score 0, adjusted 1-year MRRs for Charlson score ≥3 were 1.44 (95% CI: 0.62–3.36) in 2000–2002 and 2.11 (95% CI: 1.27-3.51) in 2009–2011, whereas adjusted 1-year MRRs for Charlson score 1–2 changed from 2.04 (95% CI: 1.33–3.14) in 2000–2002 to 1.09 (95% CI: 0.69–1.71) in 2009–2011.

Conclusion: Comorbidity increased among ovarian cancer patients over time and was associated with poor survival. One- and 5-year overall survivals changed only little and an expected decrease in survival, following increased prevalence of comorbidity and increasing age of patients, may have been counteracted by more aggressive surgery.
 

Identification of candidate circulating cisplatin-resistant biomarkers from epithelial ovarian carcinoma cell secretomes : British Journal of Cancer

Abstract

Background:

The majority of patients diagnosed with advanced epithelial ovarian carcinoma (EOC) relapse with resistant disease, and there are no biomarkers that possess clinical utility to identify or monitor these patients. This study aimed to identify secreted proteins (‘secretome’) collected from human EOC cell lines that differ in their inherent platinum sensitivity.

Methods:

Secreted proteins collected from conditioned medium from ovarian cancer cell lines that vary in their sensitivity to cisplatin were digested with trypsin and analysed by liquid chromatography-tandem mass spectrometry for peptide identification.

Results:

Of the 1688 proteins identified, 16 possessed significant differential abundances (P<0.05) between the platinum-resistant and -sensitive cell lines. A number of these were verified by immunoblot, including COL11A1, which was also found to be associated with worse progression-free survival (PFS; N=723) and overall survival (OS; N=1183) as assessed from publicly available transcript expression data from ovarian cancer tumour specimens.

Conclusion:

Secretome proteomics of EOC cells resulted in the identification of a novel candidate biomarker, COL11A1 (+search). The expression level of COL11A1 correlates to worse PFS and OS, and is predicted to reside in peripheral circulation making this an attractive candidate for validation in sera as a biomarker of cisplatin resistance and poor outcome.

 

A Study of ENMD-2076 in Ovarian Clear Cell Cancers - locations (not yet recruiting)

 ClinicalTrials.gov

Locations

United States, Pennsylvania
Fox Chase Cancer Center	Not yet recruiting
Philadelphia, Pennsylvania, United States, 19111-2497
Contact: Lainie Martin, M.D.     215-728-3889
Principal Investigator: Lainie Martin, M.D.
Canada, Alberta
Tom Baker Cancer Centre	Not yet recruiting
Calgary, Alberta, Canada, T2N 4N2
Contact: Prafull Ghatage, M.D.     403-521-3721
Principal Investigator: Prafull Ghatage, M.D.
Cross Cancer Institute	Not yet recruiting
Edmonton, Alberta, Canada, T6G 1Z2
Contact: Katia Tonkin, M.D.     780-432-8514
Principal Investigator: Katia Tonkin, M.D.
British Columbia Cancer Agency	Not yet recruiting
Vancouver, Alberta, Canada, V5Z 4E6
Contact: Anna Tinker, M.D.     604-877-6000
Canada, Ontario
Holger (Hal) Hirte	Not yet recruiting
Hamilton, Ontario, Canada, L8V 5C2
Contact: Holger (Hal) Hirte, M.D.     905-387-9495
Principal Investigator: Holger (Hal) Hirte, M.D.
London Regional Cancer Program	Not yet recruiting
London, Ontario, Canada, N6A 4L6
Contact: Stephen Welch, M.D.     519-685-8640
Principal Investigator: Stephen Welch, M.D.
Ottawa Regional Cancer Centre	Not yet recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Johanne Weberpals, M.D.     519-737-8899 ext. 76462
Principal Investigator: Johanne Weberpals, M.D.
Princess Margaret Cancer Centre	Not yet recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Amit Oza, M.D.     416-946-2818
Principal Investigator: Amit Oza, M.D.

 

Search of: clear cell ovarian | Open Studies - List Results

Blogger's Note: this was a quick search which resulted in 28 responses (1 deleted as not relevant) - a FYI:

ClinicalTrials.gov

Rank	Status	Study
1	Not yet recruiting	Imaging Tumor Hypoxia With 18F-EF5 PET in Recurrent or Metastatic Clear Cell Ovarian Cancer
2	Recruiting	Temsirolimus, Carboplatin, and Paclitaxel as First-Line Therapy in Treating Patients With Newly Diagnosed Stage III or Stage IV Clear Cell Ovarian Cancer
3	Not yet recruiting	A Study of ENMD-2076 in Ovarian Clear Cell Cancers

EntreMed Commences Phase 2 Trial For ENMD-2076 In Ovarian Clear Cell Carcinomas - WSJ.com

WSJ.com

ROCKVILLE, Md., Oct. 31, 2013 /PRNewswire/ -- EntreMed, Inc. (NASDAQ: ENMD), a clinical-stage pharmaceutical company developing therapeutics for the treatment of a variety of cancers, announced today the commencement of a multi-center Phase 2 study entitled "Phase II Study of Oral ENMD-2076 Administered to Patients with Ovarian Clear Cell Carcinomas." The study is led by principal investigator Amit M. Oza, MD at Princess Margaret Cancer Centre in Toronto, Canada with participation of up to seven additional cancer centers in Canada and the United States. More information about the clinical trial can be found at www.clinicaltrials.gov.

Amit M. Oza, MD, principal investigator of the study, commented, "Ovarian clear cell carcinomas (OCCC) account for approximately 5-13% of all epithelial ovarian cancers and compared to other subtypes, are associated with poorer prognosis and can be resistant to conventional platinum-based chemotherapy. It presents a considerable clinical challenge and there is a need to develop new therapeutics in the management of this disease. ENMD-2076 has demonstrated single agent activity in tumor models of multiple cancers including ovarian cancer. In a recent Phase 2 trial where ENMD-2076 was administered to platinum-resistant recurrent ovarian cancer patients, some OCCC patients had prolonged disease control, suggesting that it may be effective in this subset of patients. We want to explore this further. The purpose of this study is to examine the response and PFS rates of ENMD-2076 in this difficult to treat patient population. We look forward to working closely with EntreMed and colleagues from other sites in this Phase 2 trial."

Ken K. Ren, Ph.D., EntreMed's Chief Executive Officer commented, "We are very pleased to have Dr. Oza lead this trial. Dr. Oza was a principal investigator in our Phase 2 study in platinum resistant ovarian cancer and has been instrumental in advancing our development program targeting this indication. The cumulative evidence has indicated the potential effectiveness of a combined anti-angiogenic and anti-Aurora A targeted approach in OCCC, and we believe ENMD-2076 presents strong clinical and scientific rationale for the treatment of this subset of patient population. This trial will provide us with more insight into the drug's clinical activities and its correlation with biomarkers."......

Coping with Cancer: Prognosis Resources - National Cancer Institute

National Cancer Institute

1) Prognosis Resources

2) Understanding Your Cancer Prognosis

 

'Dead Man Walking': A Too Common Cancer Patient

'Dead Man Walking'

"As oncologists around the world know, the United States is the home of an enviable amount of cancer research and clinical innovation.
Physicians here and abroad also know that the New England Journal of Medicine often serves as a showcase for great clinical triumphs in American oncology.
The venerable publication regularly publishes groundbreaking cancer studies funded by the National Institutes of Health and American pharmaceutical companies that change practice.
However, a different kind of American cancer story was published online October 23 in the New England Journal of Medicine.
It even shocked 2 physicians who admit to being "accustomed" to disturbing patient tales.....
 

Coordinated Care - The Commonwealth Fund (video 2.32 min.)

Coordinated Care 

Search of: ponatinib | Adult - List Results - ClinicalTrials.gov - FDA warning Ponatinib

Search of: ponatinib | Adult - List Results - ClinicalTrials.gov


 Oct 31st:

FDA Asks Ariad to Halt Sale of Leukemia Drug

Age at Onset Should Be a Major Criterion for Subclassification of Colorectal Cancer

Abstract

Purchase $31.50

---

An important proportion of early-onset colorectal cancer (CRC) does not show a hereditary component, generally Lynch syndrome, with limited knowledge about its molecular basis and features. We analyzed a subset of patients with early-onset CRC and compared them with patients with late-onset CRC. We analyzed the microsatellite instability and CpG island methylator phenotype (CIMP) in both populations and classified them into four molecular subtypes. We analyzed the differential features between groups. Only 12 of 81 early-onset cases (15%) showed microsatellite instability, 10 of which (83%) were Lynch syndrome cases; microsatellite instability cases in elderly patients were sporadic. Early-onset microsatellite-stable cases showed different tumor locations and more family history of cancer than the elderly. Microsatellite instability/CIMP-high early-onset CRC was associated with Lynch syndrome, whereas the elderly cases were associated with BRAF mutations. Early-onset microsatellite-stable/CIMP-high CRCs were more frequently mucinous and right sided than elderly cases, with a high incidence of Lynch syndrome neoplasms; early-onset microsatellite stable/CIMP-low/0 differed from elderly cases in location, stages, incidence of multiple primary neoplasms, and the familial component. The clinical and familial differences observed between early- and late-onset CRC when considering the different carcinogenetic pathways underline that the age at onset criterion should be considered when classifying CRC.

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Herpes Zoster — NEJM (vaccine - article/commentaries)

Herpes Zoster 

Talking with Patients about Other Clinicians' Errors — NEJM

open access

Re: Risks of Colorectal and Other Cancers After Endometrial Cancer for Women With Lynch Syndrome

no abstract

J Natl Cancer Inst. 2013 Oct 29. [Epub ahead of print]

Oktay AA, Alpay SN, Sahin IH.

Source

Affiliations of authors: Department of Internal Medicine, Saint Francis Hospital, Evanston, IL (AAO); Department of Experimental Therapeutics (SNA) and Department of Gastrointestinal Medical Oncology (IHS), University of Texas MD Anderson Cancer Center, Houston, TX.

PMID:

24168969

[PubMed - as supplied by publisher]

 

Pooled cohort study on height and risk of cancer and cancer death

open access

Conclusion
Height was associated with risk of cancer and cancer death indicating that factors related to height such as hormonal and genetic factors stimulate both cancer development and progression.

Introduction
Adult height, determined by genetics and by nutrition in
childhood, has been associated with an increased risk of
some cancers such as cancer of the prostate [1], breast [2],
colorectum [3], ovary [4, 5], pancreas [6], kidney [7], testis
[8], endometrium [9], malignant melanoma [2, 10, 11], and
with lymphohematopoietic malignancies [12]. However,
there are only a few studies on all cancer sites, [2, 13–15]
and only one of these studies included men as well as
women [13]. Height has also been associated with an
increased risk of cancer death in contrast to the decreased
risk of total mortality and mortality from cardiovascular
diseases [16, 17]. To the best of our knowledge, no large
study to date has analyzed risk of cancer at all sites and
cancer death in the same study......

2014 Progress and Controversies in Gynecologic Oncology Conference (notice)

Conference

 

Seth's Blog: On owning it

Seth's Blog

Impact of anesthesia for cancer surgery

abstract

PURPOSE:

A number of original publications and review articles have addressed the issue of perioperative immune modulation and cancer outcome. The objective of this module is to review current understanding surrounding the pathways involved and the evidence implicating commonly used anesthetic agents.

PRINCIPAL FINDINGS:

Drugs commonly used in anesthetic practice have been shown to affect various components of the immune system in laboratory animal and human in vitro models. It has been hypothesized that these effects may favour tumour recurrence and metastasis formation. Inhalational agents and opiates have potential negative immunomodulatory effects; on the other hand, regional anesthesia and propofol may have positive effects on immune function modulation. However, the clinical relevance of these studies to human cancer outcome is unknown since clinical trials are equivocal, and results of in vitro and animal model studies cannot be extrapolated to clinical practice. Furthermore, there is a lack of rigorous clinical trials demonstrating clinical outcome benefit for one technique over another. It remains unclear how anesthetic drugs influence the immune system in relation to tumour cell elimination and clinical cancer outcome.

CONCLUSIONS:

Recommendations for a specific anesthetic technique based on cancer outcome alone cannot be made. A pragmatic solution would be to offer regional anesthesia in isolation or combined with propofol infusion to cancer patients if appropriate and if local expertise is available. Regional anesthesia offers excellent analgesia, a low incidence of postoperative nausea and vomiting, and a favourable immunological profile based on current understanding of laboratory evidence.

Purchase on Springer.com

$39.95 / €34.95 / £29.95

 

Americans will have an extra six weeks to buy health coverage before facing penalty

The Washington Post

Hormone Therapy’s Protection Against Endometrial Cancer Persists in Women’s Health Initiative Follow-Up Study

 Blogger's Note: post WHI studies have been published in recent years which have 'clarified' some of the original study's findings, such as this:

PracticeUpdate (requires registration to view - free)

"...Dr. Marcia Hall, a consultant medical oncologist at the Mount Vernon Cancer Centre in greater London, provided independent comment on the results. “The combination of estrogen plus progestin does indeed protect against endometrial cancer,” she said, noting that the results are in line with those of observational studies, such as the U.K.’s Million Women Study (Lancet 2007;369:1703-10)....

Scientists voice fears over ethics of drug trials remaining unpublished

media - UK

Drug companies and other organisations that carry out clinical trials are violating their ethical obligation to the people who take part by failing to publish the results, scientists will argue on Wednesday.
Almost one in three (29%) large clinical trials in the United States remain unpublished five years after they are finished, according to scientists writing in the British Medical Journal. Of those, 78% have no results at all in the public domain.
The scientists calculate about 250,000 people took part in the unpublished trials and have therefore been exposed to all the risks involved in research without the benefits to society they were led to believe would ensue. This "violates an ethical obligation that investigators have towards study participants", say Christopher Jones from the Department of Emergency Medicine, Cooper Medical School of Rowan University, New Jersey, and colleagues. They call for additional safeguards "to ensure timely public dissemination of trial data."
The researchers looked at trials registered in the United States, but some of that research will have taken place in Britain and the issue is global....
 

Marriage Is As Protective As Chemotherapy in Cancer Care

open access

See accompanying article on page 3869 

Pharmacologic Ovarian Preservation in Young Women Undergoing Chemotherapy

abstract

The prognosis of malignancies in young women undergoing chemotherapy has dramatically improved recently, and more attention is given to the long term quality of life, including fertility and reproductive function preservation. Some chemotherapeutic drugs are known to be associated with gonadal toxicity (cyclophosphamide, L-phenylanine mustard, busulfan and nitrogen mustard) and others have less or un-quantified effects (doxorubicin, bleomycin, vinca alkaloids, as vincristine and vinblastin, cisplatin, nitrosoureas, cytosine arabinoside). Women are in need to identify best options to minimize ovarian damage during chemotherapy through the administration of protective drugs, better choice of therapy and with advocating oncofertility preservation. We reviewed the possible options focusing on the most studied gonadotrophin-releasing hormone agonists (GnRH-a) and the psychologically promising oral contraceptives (OC). Controversy exist on the benefit of gonadotrophin releasing hormone agonist (GnRH-a) or combined oral contraceptive administered at time of cancer therapy in preventing premature ovarian failure in women and the available data from both human and animal studies have been mixed. The best way to preserve fertility and ovarian function in young women undergoing chemotherapy still remains to be determined. In the absence of a best approach, each case should be evaluated individually, considering patient's wishes and expectations, the type of chemotherapy, age, obstetric history, ovarian reserve (combining multiple indicators such as basal hormone profile, anti müllerian hormone -AMH- and antral follicle count), family history of premature ovarian failure. We present a review of the available evidence on the value of administering GnRH-a and OC use to minimize or prevent the effect of chemotherapy agents on reproductive function.

 

Intraperitoneal chemotherapy: Rationale, applications, and limitations (Saudi Arabia)

abstract

 

Intraperitoneal chemotherapy, involving the administration of certain chemotherapeutic agents directly to the intraperitoneal cavity, was developed as a novel therapeutic strategy early in the 1950s. Intraperitoneal administration of chemotherapy results in higher intraperitoneal concentration of the cytotoxic medications and minimal systemic exposure than observed with intravenous administration, which in turn may increase the efficacy of these agents with substantial reduction in systemic toxicity. Intraperitoneal chemotherapy was used successfully in peritoneal surface malignancies, including malignant peritoneal mesothelioma, pseudomyxoma peritonei, malignant ascites, sarcomatosis, and peritoneal carcinomatosis from gastrointestinal and ovarian cancers. Pharmacists may play a major role in optimizing intraperitoneal chemotherapy through verification of chemotherapy order for proper doses, dilution, preparation, and administration. Moreover, pharmacists are medication experts who can provide other health care professionals with the necessary drug information.

Despite the local application of chemotherapy, intraperitoneal chemotherapy is not free of systemic side effects and can be associated with serious complications. The benefits of intraperitoneal chemotherapy should be weighed against its potential harm to maximize efficacy and to minimize morbidity and mortality as much as possible. The aim of this article is to review the current available literature regarding the safety and efficacy of intraperitoneal chemotherapy in cancer treatment.

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Feasibility, acceptability and preferences for intraperitoneal chemotherapy with paclitaxel and cisplatin after optimal debulking surgery for ovarian and related cancers: an ANZGOG study

open access

Abstract

Objective: Intraperitoneal (IP) chemotherapy in women with optimally debulked stage III ovarian cancer has been reported to prolong overall survival, but has not been widely adopted due to concerns about its toxicity, inconvenience and acceptability to patients. The purposes of this study were to determine the regimen's feasibility, adverse events, catheter-related complications, progression-free survival, health-related quality of life (HRQL), and patients' preferences for IP versus intravenous (IV) chemotherapy.
Methods: We conducted a single arm, multi-center study of IP chemotherapy with IV paclitaxel 135 mg/m2 (D1) over 3 hours, IP cisplatin 75 mg/m2 (D2), and IP paclitaxel 60 mg/m2 (D8) for 6 cycles in women with optimally debulked stage III ovarian or related cancers.
Results: Thirty-eight eligible patients were recruited from 12 sites between July 2007 and December 2009. Seventy-one percent (n=27) completed at least 4 cycles and 63% (n=24) completed all 6 cycles. Grade 3 or 4 adverse events included nausea (n=2), vomiting (n=2), abdominal pain (n=2), and diarrhea (n=1), but not febrile neutropenia, neurotoxicity, or nephropathy. There were no treatment-related deaths. Catheter-related complications were the most frequent cause of early discontinuation of treatment (16 patients, 21%). Apart from neurotoxicity HRQL which worsened over time, HRQL was stable or improved with time. Most patients (≥50%) judged moderate benefits (e.g., an extra 6 months survival time or a 5% improvement in survival rates) necessary to make IP chemotherapy worthwhile.
Conclusion: IP chemotherapy was feasible, tolerable, and most participants considered moderate survival benefits sufficient to warrant the adverse effects and inconvenience.

 

PDF open access

 

The roles of ARID1A in gynecologic cancer

 open access




 Received Aug 6, 2013, Accepted Aug 7, 2013
This article was solicited and has not been peer reviewed

CONCLUSION
Disorganized chromatin structure is known to be associated
with the appearance of various abnormal phenotypes,
including cancer [53,54]. ARID1A , a gene participated in
chromatin remodeling, is an emerging tumor suppressor
gene. Accumulating evidence has reported somatic inactivating
mutations of ARID1A and loss of its expression in many
types of human cancers, especially in endometrium-derived
tumors, including ovarian clear cell carcinomas, ovarian endometrioid
carcinomas and uterine endometrioid carcinomas.
The high prevalence of somatic mutations in those ovarian
and endometrial cancers indicates a pivotal role of ARID1A in
their development. Understanding the roles of ARID1A in the
pathogenesis of endometrium-derived tumors is fundamental
for future translational studies aimed at designing new
diagnostic tests for early detection and identifying critical
molecular targets for new therapeutic interventions.

Parameters that Define A Successful Colonoscopy

open access (see tables 1 & 2)

Dose-dense effect: other contributors – Author's reply : The Lancet Oncology

abstract

"Kesikli and colleagues argued that results shown by the JGOG 3016 study for dense-dense paclitaxel in ovarian cancer 1 were caused by a higher cumulative dose received by the dose-dense group and by antiangiogensis effects of paclitaxel rather than by the dose-dense administration of the drug. However, increased dose of paclitaxel in ovarian cancer has shown no survival benefit in previous studies. Bolis and colleagues 2 compared standard-dose paclitaxel 175 mg/m 2 plus carboplatin with increased dose ... (to read further requires $$$)

 

Untangling BRCA mutations, sex hormones, and cancer risk : The Lancet Oncology

open access

Understanding basic disease mechanisms might allow development of novel strategies for the primary prevention of breast and ovarian cancer. For carriers of BRCA1/2 mutations, options for primary prevention are limited to bilateral salpingo-oophorectomy and prophylactic mastectomy. In The Lancet Oncology, Martin Widschwendter and colleagues1 compare ovarian and endometrial function in carriers of the BRCA1/2 mutation with high-risk, mutation negative women in the UK Familial Ovarian Cancer Screening Study. BRCA1/2 mutations are thought to cause cancer via a defect in DNA damage response or in the DNA repair pathway, but this does not explain organ-specific cancer penetrance. These novel data suggest that end-organ response might have a role..... 

The CONSORT Patient-Reported Outcome (PRO) extension: implications for clinical trials and practice

open access

Health and Quality of Life Outcomes (multi-national)

To inform clinical guidelines and patient care we need high quality evidence on the relative benefits and harms of intervention. Patient reported outcome (PRO) data from clinical trials can "empower patients to make decisions based on their values" and "level the playing field between physician and patient". While clinicians have a good understanding of the concept of health-related quality of life and other PROs, evidence suggests that many do not feel comfortable in using the data from trials to inform discussions with patients and clinical practice. This may in part reflect concerns over the integrity of the data and difficulties in interpreting the results arising from poor reporting.The new CONSORT PRO extension aims to improve the reporting of PROs in trials to facilitate the use of results to inform clinical practice and health policy. While the CONSORT PRO extension is an important first step in the process, we need broader engagement with the guidance to facilitate optimal reporting and maximize use of PRO data in a clinical setting. Endorsement by journal editors, authors and peer reviewers are crucial steps. Improved design, implementation and transparent reporting of PROs in clinical trials are necessary to provide high quality evidence to inform evidence synthesis and clinical practice guidelines. 

Background
Randomized controlled clinical trials (RCTs) can provide high-quality data regarding the impact of study interventions on patient outcomes, and remain the ‘gold standard’ of evidence regarding both the benefits and harms associated with an intervention. Over the last twenty years, the number of clinical trials that assess patient reported outcomes (PROs) has
substantially increased [1]. PROs can be defined as a “measurement of any aspect of a patient’s health status that comes directly from the patient (i.e. without the interpretation of the patient’s responses by a physician or anyone else” [2] and include health-related quality
of life (HRQL), symptoms, satisfaction and adherence to medication. These subjective measures of outcome help evaluate the burden of disease and treatment from the patients’ perspective. In the conceptual framework developed by Till and colleagues adapted in (Figure 1) [3], PRO data from clinical trials may directly inform patients and practitioners, or may indirectly inform clinical practice through evidence synthesis into clinical practice guidelines.....

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

 

Choosing Wisely Campaign: American Society of Clinical Oncology 2013 Top Five List in Oncology

ASCO - open access

Medical News |

Physician's First Watch

October 30, 2013

5 Cancer Tests and Treatments with Little or No Value

By Joe Elia

The American Society of Clinical Oncology has identified a second group of commonly used tests and treatments in cancer medicine that have little or no benefit. The list, part of the American Board of Internal Medicine's "Choosing Wisely" initiative, appears in the Journal of Clinical Oncology.

Briefly, here are this year's "top five" items:

• Don't give antiemetics to patients starting chemotherapies that have low-to-moderate potential for causing symptoms.
• In treating metastatic breast cancer, avoid combination chemotherapy unless the patient's cancer burden needs to be reduced quickly.
• Avoid PET scanning in routine follow-up unless there's "high-level" evidence that the imaging will improve outcomes.
• Don't do PSA testing in asymptomatic men when life expectancy is under 10 years.
• Don't use therapy targeted against a specific genetic aberration unless the patient has specific biomarkers that predict effective response.

Link(s):

Journal of Clinical Oncology article (Free PDF)

Background: ASCO's 2012 choices (Free)

Choosing Wisely home page (Free)

- See more at: http://www.jwatch.org//fw108085/2013/10/30/5-cancer-tests-and-treatments-with-little-or-no-value#sthash.E2u68UGy.dpuf

Medical News |

Physician's First Watch

October 30, 2013

5 Cancer Tests and Treatments with Little or No Value

By Joe Elia

The American Society of Clinical Oncology has identified a second group of commonly used tests and treatments in cancer medicine that have little or no benefit. The list, part of the American Board of Internal Medicine's "Choosing Wisely" initiative, appears in the Journal of Clinical Oncology.

Briefly, here are this year's "top five" items:

• Don't give antiemetics to patients starting chemotherapies that have low-to-moderate potential for causing symptoms.
• In treating metastatic breast cancer, avoid combination chemotherapy unless the patient's cancer burden needs to be reduced quickly.
• Avoid PET scanning in routine follow-up unless there's "high-level" evidence that the imaging will improve outcomes.
• Don't do PSA testing in asymptomatic men when life expectancy is under 10 years.
• Don't use therapy targeted against a specific genetic aberration unless the patient has specific biomarkers that predict effective response.

Link(s):

Journal of Clinical Oncology article (Free PDF)

Background: ASCO's 2012 choices (Free)

Choosing Wisely home page (Free)

- See more at: http://www.jwatch.org//fw108085/2013/10/30/5-cancer-tests-and-treatments-with-little-or-no-value#sthash.E2u68UGy.dpuf

Medical News |

Physician's First Watch

October 30, 2013

5 Cancer Tests and Treatments with Little or No Value

By Joe Elia

The American Society of Clinical Oncology has identified a second group of commonly used tests and treatments in cancer medicine that have little or no benefit. The list, part of the American Board of Internal Medicine's "Choosing Wisely" initiative, appears in the Journal of Clinical Oncology.

Briefly, here are this year's "top five" items:

• Don't give antiemetics to patients starting chemotherapies that have low-to-moderate potential for causing symptoms.
• In treating metastatic breast cancer, avoid combination chemotherapy unless the patient's cancer burden needs to be reduced quickly.
• Avoid PET scanning in routine follow-up unless there's "high-level" evidence that the imaging will improve outcomes.
• Don't do PSA testing in asymptomatic men when life expectancy is under 10 years.
• Don't use therapy targeted against a specific genetic aberration unless the patient has specific biomarkers that predict effective response.

Link(s):

Journal of Clinical Oncology article (Free PDF)

Background: ASCO's 2012 choices (Free)

Choosing Wisely home page (Free)

- See more at: http://www.jwatch.org//fw108085/2013/10/30/5-cancer-tests-and-treatments-with-little-or-no-value#sthash.E2u68UGy.dpuf

Fruit and vegetable consumption associated with reduced risk of epithelial ovarian cancer in southern Chinese women

abstract

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Highlights

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First report on fruit and vegetable intake and ovarian cancer in southern China.

•

High fruit and vegetable consumption appears protective against ovarian cancer.

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Intakes of nutrients derived from fruits and vegetables are inversely associated with the ovarian cancer risk.

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Objective

To investigate the association between fruit and vegetable consumption and the risk of epithelial ovarian cancer in southern Chinese women.

Methods

A case-control study was undertaken in Guangzhou, Guangdong Province, between 2006 and 2008. Participants were 500 incident ovarian cancer patients and 500 hospital-based controls. Information on habitual fruit and vegetable consumption was obtained by face-to-face interview using a validated and reliable food frequency questionnaire. Unconditional logistic regression analyses were performed to assess the association between fruit and vegetable intakes and the ovarian cancer risk.

Results

The mean fruit and vegetable daily intakes of ovarian cancer patients (324.2 g (SD 161.9) and 582.7 g (SD 250.2)) were significantly lower (p < 0.001) than those of controls (477.3 g (SD 362.1) and 983.3 g (SD 739.9)). The adjusted odds ratios were 0.30 (95% confidence interval (CI) 0.21 to 0.44) and 0.07 (95% CI 0.04 to 0.12) for more than 490 g of fruits and 970 g of vegetables per day, relative to at most 320 g and 690 g per day, respectively. With the exception of lycopene, substantial risk reductions were evident for a variety of nutrients derived from fruits and vegetables.

Conclusion

Consumption of fruits and vegetables was inversely associated with the incidence of epithelial ovarian cancer in southern Chinese women.

 

Pelvic MRI as the “gold standard” in the subsequent evaluation of ultrasound-indeterminate adnexal lesions: A systematic review

abstract

Review

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Highlights

•

The preponderant contribution of MRI in adnexal mass evaluation is its specificity.

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Pelvic MRI provides confident diagnosis of a plethora of benign adnexal lesions.

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Contrast-MRI provides the highest post-test probability of ovarian cancer detection.

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Objective

Incidentally discovered adnexal masses are common, posing a challenging diagnostic problem due to overlapping imaging features of benign and malignant. Thus, once an adnexal lesion has been detected, the primary goal of further imaging is accurate tissue characterization resulting in surgery only for lesions that are indeterminate or frankly malignant. This study aims to conduct a systematic review, following the PRISMA guidelines, and critically appraise pelvic MR Imaging as the preferred advanced second imaging test, as regards detection of ovarian cancer and assessment of indeterminate adnexal masses, with respect to pre-operatively improving the assignment of these patients to the appropriate level of care.

Methods

A comprehensive computerized systematic literature search of English language studies was performed (from 2002 to 2012) of PubMed, EMBASE, Scopus, Evidence Based Medicine Reviews (Cochrane Database and Cochrane Central Register of Controlled Trials), and Google Scholar. Relevant article reference lists were hand searched.

Results

Computerized database search revealed 37 citations of relevance, 10 of which fulfilled the inclusion/exclusion criteria. From the aforementioned, 8 articles were acquired (2 authors were contacted but did not respond) as well as assessed with AHRQ, QUADAS, and STARD evaluation tools. Finally, 6 papers (5 prospective and 1 retrospective) were included in the systematic review.

Conclusions

MRI with intravenous (IV) contrast administration provides the highest post-test probability of ovarian cancer detection. However, the preponderant contribution of MRI in adnexal mass evaluation is its specificity because it provides confident diagnosis of many benign adnexal lesions.

 

The Role and Timing of Palliative Medicine Consultation for Women with Gynecologic Malignancies: Association with End of Life Interventions and Direct Hospital Costs (NY)

abstract

Open Access (pdf)

"Palliative care is often confused with hospice care."

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Highlights

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Timely palliative medicine consultation is associated with improved quality of end of life care.

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Decreased direct hospital costs are associated with timely palliative medicine consultation.

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Objective

Aggressive care interventions at the end of life (ACE) are reported metrics of sub-optimal quality of end of life care that are modifiable by palliative medicine consultation. Our objective was to evaluate the association of inpatient palliative medicine consultation with ACE scores and direct inpatient hospital costs of patients with gynecologic malignancies.

Methods

A retrospective review of medical records of the past 100 consecutive patients who died from their primary gynecologic malignancies at a single institution was performed. Timely palliative medicine consultation was defined as exposure to inpatient consultation ≥ 30 days before death. Metrics utilized to tabulate ACE scores were ICU admission, hospital admission, emergency room visit, death in an acute care setting, chemotherapy at the end of life, and hospice admission < 3 days. Inpatient direct hospital costs were calculated for the last 30 days of life from accounting records. Data were analyzed using Fisher’s Exact, Mann–Whitney U, Kaplan-Meier, and Students T testing.

Results

49% of patients had a palliative medicine consultation, 18% had timely consultation. Median ACE score for patients with timely palliative medicine consultation was 0 (range 0–3) versus 2 (range 0–6) p = 0.025 for patients with untimely/ no consultation. Median inpatient direct costs for the last 30 days of life were lower for patients with timely consultation, $0 (range 0–28,019) versus untimely, $7729 (0–52,720), p = 0.01.

Conclusions

Timely palliative medicine consultation was associated with lower ACE scores and direct hospital costs. Prospective evaluation is needed to validate the impact of palliative medicine consultation on quality of life and healthcare costs.

Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Targeting and Relevant Biomarkers in Ovarian Carcinoma (IMC-3G3)

abstract

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Highlights

•

Targeting PDGFRα with monoclonal antibody (IMC-3G3) significantly enhanced the efficacy of chemotherapy in ovarian cancer cells both in-vitro and in-vivo.

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Ovarian cancer cells with high-PDGFRα expression showed significant antitumor effects with IMC-3G3 monotherapy, whereas those expressing low-PDGFRα did not.

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MAPK and CCNB1 were associated with response to IMC-3G3 in high-PDGFRα cells that showed antitumor effects with IMC-3G3 monotherapy.

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Objective

Platelet-derived growth factor receptor alpha (PDGFRα) is believed to be associated with cell survival. We examined (i) whether PDGFRα blockade enhances the antitumor activity of taxanes in ovarian carcinoma and (ii) potential biomarkers of response to anti-PDGFRα therapy.

Methods

PDGFRα expression in 176 ovarian carcinomas was evaluated with tissue microarray and correlated to survival outcome. Human-specific monoclonal antibody to PDGFRα (IMC-3G3) was used for in vitro and in vivo experiments with or without docetaxel. Gene microarrays and reverse-phase protein arrays with pathway analyses were performed to identify potential predictive biomarkers.

Results

When compared to low or no PDGFRα expression, increased PDGFRα expression was associated with significantly poorer overall survival of patients with ovarian cancer (P = 0.014). Although treatment with IMC-3G3 alone did not affect cell viability or increase apoptosis, concurrent use of IMC-3G3 with docetaxel significantly enhanced sensitization to docetaxel and apoptosis. In an orthotopic mouse model, IMC-3G3 monotherapy had no significant antitumor effects in SKOV3-ip1 (low PDGFRα expression), but showed significant antitumor effects in HeyA8-MDR (high PDGFRα expression). Concurrent use of IMC-3G3 with docetaxel, compared with use of docetaxel alone, significantly reduced tumor weight in all tested cell lines. In protein ontology, the EGFR and AKT pathways were downregulated by IMC-3G3 therapy. MAPK and CCNB1 were downregulated only in the HeyA8-MDR model.

Conclusion

These data identify IMC-3G3 as an attractive therapeutic strategy and identify potential predictive markers for further development.