Studies Reignite Debate over Avastin (Bevacizumab) in Breast Cancer - in Oncology/Hematology, Breast Cancer from MedPage Today

Action Points

---

• These two studies found a benefit in the surrogate endpoint of complete pathologic response with the addition of bevacizumab in neoadjuvant treatment for HER2-negative breast cancer.



• Note that pathologic complete response was defined differently in the two studies -- in the breast and nodes in one and only in the breast in the other; applying the more stringent breast-plus-nodes criterion in the second study eliminated the statistical significance.

WCIO - World Conference on Internventional Oncology conference announcement - Chicago June 14-17

The World Conference on Interventional Oncology is the largest interventional oncology meeting in the United States. More than 500 attendees are expected to attend WCIO 2012, which is scheduled 14 - 17 June at the Sheraton Chicago Hotel and Towers in Chicago, Illinois, USA.

abstract: Nodular Histiocytic Aggregates in the Greater Omentum of Patients With Ovarian Cancer

"This report has first demonstrated visible NHA in the greater omentum of patients with ovarian malignancies, and awareness of this entity should be brought to clinicians to avoid misdiagnosis."

full text Editorial (plus link to abstract (paper) - Does Cancer Treatment in Childhood Induce Transgenerational Genetic Damage?

Editorial:

"Because childhood cancer and many of the selected outcomes are rare, both studies were limited by small numbers, although they are among the largest to date, given that they include survivors from 26 participating research centers in North America and Canada and all survivors of childhood cancer in the country of Denmark, respectively. The relatively small number of outcomes to evaluate does result in low precision in risk estimates, especially for subgroups. By setting up an international study of transgenerational effects of cancer treatment (the Genetic Consequences of Cancer Treatment study involving researchers from both groups¹³), the sample size was increased by adding the offspring of cancer survivors diagnosed in early adulthood in both Denmark and Finland. This study is expected to provide more definitive answers to questions about the integrity of the germline in human populations that have been exposed to mutagenic cancer therapy."

Abstract/link:
ORIGINAL REPORTS - Pediatric Oncology: Congenital Anomalies in the Children of Cancer Survivors: A Report From the Childhood Cancer Survivor Study

• JCO Jan 20, 2012:239-245
  
  Conclusion:  Our findings offer strong evidence that the children of cancer survivors are not at significantly increased risk for congenital anomalies stemming from their parent's exposure to mutagenic cancer treatments. This information is important for counseling cancer survivors planning to have children.  
  
  
  
  

open access: Genome Biology - Implications for health and disease in the genetic signature of the Ashkenazi Jewish population

Blogger's Note: search results = null for 'ovarian'/'brca'

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

abstract: Antiangiogenic Agents in Combination With Chemotherapy for the Treatment of Epithelial Ovarian Cancer

Objective: The purpose of this review was to provide an overview of angiogenesis, including the rationale for targeting angiogenesis as a treatment strategy for epithelial ovarian cancer (EOC) and to discuss available clinical trial data with antiangiogenic agents in EOC, with a focus on combinations with chemotherapy.

Methods: This was a literature review of clinical studies evaluating select antiangiogenic agents in combination with traditional cytotoxic chemotherapy for the treatment of EOC.

Results: Several therapies that target angiogenesis-specific pathways are undergoing clinical development for EOC. Although some of these agents have demonstrated single-agent activity for EOC, there is considerable interest in combining this treatment strategy with chemotherapy in an effort to potentially improve treatment benefits in this patient population. Bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody, is the most studied antiangiogenic agent in EOC and has shown efficacy as monotherapy and combined with chemotherapy in both the relapsed/recurrent and first-line settings. However, results from recent phase 3 trials raise questions regarding patient selection and optimal dose, schedule, and duration of bevacizumab therapy. Other agents in various phases of testing include aflibercept (VEGF Trap), a fusion protein that binds all isoforms of VEGF; multitargeted antiangiogenic tyrosine kinase inhibitors (eg, BIBF 1120, cediranib, pazopanib, sorafenib); and AMG 386, a selective angiopoietin inhibitor. Toxicities associated with VEGF inhibition are also a concern with antiangiogenic therapy, including hypertension, proteinuria, thromboses, and gastrointestinal perforation.

Conclusions: Results from recently completed and ongoing clinical trials combining antiangiogenic agents with chemotherapy are awaited in hopes of expanding therapeutic options for patients with EOC.

Johnson & Johnson Profit Slumps 89% on Charges - WSJ.com (references to Doxil/drug shortages)

"Mr. Weldon said J&J learned a "painful lesson" from the ongoing supply shortage for its drug Doxil, which treats ovarian and other cancers, and will try to have better contingency plans to avoid such disruptions in the future.
J&'s sole supplier for Doxil, Ben Venue Laboratories, late last year suspended production at its Ohio plant to focus on fixing manufacturing deficiencies cited by government regulators, including contamination. Ben Venue, a unit of Boehringer Ingelheim GmbH, doesn't expect to have new Doxil supplies until late 2012............"

abstract: All’s Well That Ends Well? Quality of Life and Physical Symptom Clusters in Long-Term Cancer Survivors Across Cancer Types (EORTC QLQ-C30)

Blogger's Note: per abstract it does not appear ovarian cancer patients were included in this study, full access requires subscription ($$$) 

 Conclusion

Contrary to expectations, no symptom clusters specific to one type of cancer were identified and survivors reported few cancer-related symptoms and high QoL. These results convey a strong “good news” message, providing health professionals with a sound foundation for making encouraging predictions about their patients’ long-term physical recovery after cancer. Cancer patients also will welcome the news that only a minority of five-year survivors experience long-term and late effects.

Could The Key To Cancer Be Patterns Of Chromosome Abnormality? Medical News Today MNT

"Now Prof. Shamir and his former doctoral students Michal Ozery-Flato and Chaim Linhart, along with fellow researchers Prof. Shai Izraeli and Dr. Luba Trakhtenbrot from the Sheba Medical Center, have combined techniques from computer science and statistics to discover that many chromosomal pairs are lost or gained together across various cancer types."
"Under normal circumstances, even a small change to a person's chromosomal structure can be devastating. For example, Down's syndrome is caused by a single extra copy of Chromosome 21. "But in cancer, there are many cases of extra or missing chromosomes. Yet cancer cells thrive more effectively than other cells," Prof. Shamir says."

a FYI: what others were reading (in order of most viewed 1-5) - Ovarian Cancer and Us blog Jan 24th 2012

open access: Journal of Translational Medicine - Supporting the advancement of science: Open access publishing and the role of mandates (the Research Works Act[1])

open access: PLoS Medicine: Challenging Medical Ghost Writing...

abstract: Weekly paclitaxel as a single agent or i...

Medical News: BRCA Mutations Also Play Good Role i...

Expanding the Definition of Depression - Does grief...

Depression’s Criteria May Be Changed to Include Grieving - When does a broken heart become a diagnosis? NYTimes.com

"In a bitter skirmish over the definition of depression, a new report contends that a proposed change to the diagnosis would characterize grieving as a disorder and greatly increase the number of people treated for it.

The criteria for depression are being reviewed by the American Psychiatric Association, which is finishing work on the fifth edition of its Diagnostic and Statistical Manual of Mental Disorders, or D.S.M., the first since 1994. The manual is the standard reference for the field, shaping treatment and insurance decisions, and its revisions will affect the lives of millions of people for years to come......"

Expanding the Definition of Depression - Does grieving over a loved one constitute full-blown depression? NYTimes.com

Medical News: BRCA Mutations Also Play Good Role in Ovarian Cancer - in Oncology/Hematology, Ovarian Cancer from MedPage Today

Action Points

---

• A pooled analysis of 26 observational studies found that five-year survival was significantly improved for invasive epithelial ovarian cancer patients carrying BRCA1 or BRCA2 mutations compared with noncarriers.



• Note that data on treatment differences among the heterogeneous population were not available, there were missing data, and procedures for screening for the mutations differed among the studies.

abstract: Intracranial hemorrhage in patients with cancer treated with bevacizumab (Avastin) : the Memorial Sloan-Kettering experience

Background: Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor approved for recurrent glioblastoma (GBM), metastatic breast, colorectal and non-small-cell lung cancers (NSCLC). There has been a potentially increased risk of intracranial hemorrhage (ICH) in patients receiving bevacizumab.

Methods: We retrospectively identified patients with ICH who received bevacizumab between 1 January 2001 and 10 January 2009.

Results: We identified 1024 patients with ICH, 4191 patients who received bevacizumab and 12 (0.3%) who met both our criteria. There were eight women and four men with a median age of 66 years. Primary cancers were ovarian (n = 3), NSCLC (n = 3), colon (n = 1), angiosarcoma (n = 1) and GBM (n = 4). Intracranial tumors were present in 9 of the 12 patients; the remaining three (25%) had no evidence of intracranial pathology. Two hundred and fifty-seven patients with these same primary pathologies and brain tumors were treated with bevacizumab; ICH was seen in nine (3.7%), which was comparable to the 3.6% frequency seen in comparable patients not receiving bevacizumab.

Conclusions: ICH with bevacizumab treatment in this population is rare and does not appear to increase its frequency over the baseline rate of ICH in a comparable population. Most bevacizumab-related ICH occurs into central nervous system tumors but spontaneous hemorrhages were seen.

abstract: Weekly paclitaxel as a single agent or in combination with carboplatin or weekly topotecan in patients with resistant ovarian cancer: the CARTAXHY randomized phase II trial (GINECO)

Conclusions: Combination chemotherapy in platinum-resistant ROC (recurrent ovarian cancer) was more toxic than weekly paclitaxel and did not significantly prolong PFS.

open access: Cancer of unknown primary (CPU) : progress in the search for improved and rapid diagnosis leading toward superior patient outcomes

Abstract

This paper explores the enigma of cancer of unknown primary (CUP) in relation to rapidly improving molecular diagnostic approaches. It is based on the first global collaboration meeting on improving research and clinical outcomes in CUP organized by the CUP Foundation........All patients with CUP could thus be appropriately managed without the constant uncertainty that has previously severely hampered patient care and optimal outcomes. The longer-term objective is to understand the biology of highly metastatic disease, leading to the development of future global therapeutic programs. Current clinical studies, such as CUP-ONE, will address some of these issues.

introduction

definition, epidemiology, biology, and prognosis

diagnostic approaches to CUP

pathologic evaluation

clinical evaluation

molecular profiling and classification of human cancers

new technologies in practice

conclusion

 

"....Several of the favorable subsets of CUP patients seem to mimic the clinical and pathologic features of particular known metastatic cancers. These include ..............; peritoneal serous adenocarcinoma (ovarian primary) ........" 

Table 1.    Favorable prognostic subsets of patients with unknown primary cancer recognized by clinical and pathologic features in the last three decades

 

Letters (2)/Response: BRCA1 and BRCA2 Mutations in Ovarian Cancer, January 25, 2012 — JAMA

Blogger's Note: to view full response subscription req'd ($$$)

Letter #1
Letter #2
Author Response

open access: PLoS Medicine: Challenging Medical Ghostwriting in US Courts - eg. ethics, legal liabilities, patient harm.....

Introduction

"Complaints about the ethics of medical ghostwriting have increased in the last decade, but little has changed [1]–[14]....."

Summary Points

• Despite growing concern about medical ghostwriting, pharmaceutical companies, universities, medical journals, and communication companies employing ghostwriters have thus far failed to adequately stem the problem. As a result, some commentators have proposed that legal remedies could be sought by patients harmed by drugs publicized in ghostwritten papers.
• In this Essay, we build on a recent analysis by Stern and Lemmens in PLoS Medicine to outline specific areas of legal liability.
• For example, when an injured patient's physician directly or indirectly relies upon a journal article containing false or manipulated safety and efficacy data, the authors, including guest authors, can be held legally liable for patient injuries.
• In addition, guest authors of ghostwritten articles published by Medicare- and Medicaid-recognized peer-reviewed medical journals used as clinical evidence for indications for off-label uses may be liable under the federal False Claims Act for inducing the United States government to reimburse prescriptions under false pretenses.
• Paying guest authors of ghostwritten papers may influence clinical judgment, increase product sales and government health care costs, and put patients at risk by misrepresenting risk-benefit. Therefore, both physicians and sponsor companies may be liable under the federal Anti-Kickback Statute.
• Although guest authors and pharmaceutical defendants may argue a First Amendment right to participate in ghostwriting, the US Supreme Court has firmly held that the First Amendment does not shield fraud.

Author Insights: BRCA1 and BRCA2 Gene Mutations Associated With Improved Ovarian Cancer Survival « news@JAMA

"....The pooled analysis of 26 observational studies involving 3879 women with ovarian cancer found 52% of women with a BRCA2 mutation were alive 5 years after diagnoses, as were 44% of women with a BRCA1 mutation........ The researchers noted that the survival advantage seen in women carrying a BRCA1 or BRCA2 mutation could be related to “intrinsic biological differences, their response to therapeutic agents, or both.”"

Conclusion Among patients with invasive EOC, having a germline mutation in BRCA1 or BRCA2 was associated with improved 5-year overall survival. BRCA2 carriers had the best prognosis. 

financial: California University's health unit acquires Nevada Cancer Institute

new website: Peerage of Science (for scientists/peer review))

Peerage of Science…

…is not doing “open peer review”. It provides anonymous peer review, by qualified scientists only. While a Peer can invite anyone to join, the right to access and review work done by others is given only after service administration has verified identity and qualifications (at least one published article where the new Peer is first or corresponding author, in a peer-reviewed international journal).
…is not a “pre-print server” like arXiv.org or Nature Preprints. It is closed to the outside world. It strictly limits access to manuscript under peer review to only editors and those Peers involved in that particular peer review, and does not archive manuscripts to be accessed after peer review.
…is not providing an “alternative publishing model”. It is only concerned with providing better peer review for the benefit of everyone involved, including the publishing companies.
…is not charging fees from scientists.

open access: Journal of Translational Medicine - Supporting the advancement of science: Open access publishing and the role of mandates (the Research Works Act[1])

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

excerpt pdf file:

"In December 2011 the United States House of Representatives introduced a new bill, the Research Works Act (H.R.3699), which if passed could threaten the public’s access to US government funded
research. In a digital age when professional and lay parties alike look more and more to the online environment to keep up to date with developments in their fields, does this bill serve the best
interests of the community? Those in support of the Research Works Act argue that government open access mandates undermine peer-review and take intellectual property from publishers without compensation, however journals like Journal of Translational Medicine show that this is not the case. Journal of Translational Medicine in affiliation with the Society for Immunotherapy of Cancer demonstrates how private and public organisations can work together for the advancement
of science.

Editorial

Journal of Tra nslational Medicine is an open access journal published by BioMed Central that aims to optimise communication between basic and clinical science. Now in its 10th year of publication
the journal is successful in its aim for fostering communication from bench to bedside.
A new bill, the Research Works Act[1], has been introduced in the United States House of Representatives threatening the public’s access to US government funded research and the foundation on which Journal of Translational Medicine was built.

The bill states:

“No Federal agency may adopt, implement, maintain, continue, or otherwise engage in any policy, program, or other activity that:
(1) causes, permits, or authorizes network dissemination of any private-sector research work without the prior consent of the publisher of such work; or (2) requires that any actual or prospective author, or the employer of such an actual or prospective author, assent to network dissemination of a private-sector research work.”

If passed, this bill would force the retraction of the public access policy of the National Institutes of Health[2], who mandate that recipients of their grants must make their published research publically accessible by depositing full-text versions in open access repositories (such as PubMed Central), and prevent similar policies from being introduced by federal agencies in the future.

It is argued [3, 4] that research funded by tax-payers should be made available to the public free of charge so that the tax-payer does not in effect pay twice for the research - first for the research to be done and then to read the results. As much as this may be true, the biggest detriment seems to be to developments in science. Open access to research means the widest possible dissemination of information. Limiting access to a (by comparison) small subset of people with subscriptions can stunt further developments......"

abstract: Balancing repair and tolerance of DNA damage caused by alkylating agents : Nature Reviews Cancer

Blogger's Note: requires subscription ($$$)

Quest Diagnostics Reports Fourth Quarter 2011 Financial Results; Provides Guidance for 2012 -- MADISON, N.J., Jan. 24, 2012 /PRNewswire/ --

press release: InSightec Submits Pre Market Application (PMA) for FDA Approval of ExAblate for Treatment of Painful Bone Metastases | Press Release | Rehab Management

"....ExAblate is the only MRgFUS system with FDA approval, granted in 2004 for uterine fibroids. It also received European CE marking for uterine fibroids, bone metastases, and adenomyosis. Clinical trials are ongoing for brain disorders, including essential tremor and Parkinson's disease, and prostate cancer."

abstract - Current Obstetrics and Gynecology Reports: Ovarian Cancer is an Imported Disease: Fact or Fiction?

Abstract

The cell of origin of ovarian cancer has been long debated. The current paradigm is that epithelial ovarian cancer (EOC) arises from the ovarian surface epithelium (OSE). OSE is composed of flat, nondescript cells more closely resembling the mesothelium lining the peritoneal cavity. In light of various histologic types of ovarian carcinoma (serous, endometrioid, and clear cell carcinoma), which have a Müllerian phenotype, it has been argued that the OSE undergoes a process termed “metaplasia” to account for this profound morphologic transformation.

Recent molecular and clinicopathologic studies not only have failed to support this hypothesis but also have provided evidence that EOC stems from Müllerian-derived extraovarian cells that involve the ovary secondarily, thereby calling into question the very existence of primary EOC.

This new model of ovarian carcinogenesis proposes that fallopian tube epithelium (benign or malignant) implants on the ovary to give rise to both high-grade and low-grade serous carcinomas, and that endometrial tissue implants on the ovary and produces endometriosis, which can undergo malignant transformation into endometrioid and clear cell carcinoma.

Thus, ultimately EOC is not ovarian in origin but rather is secondary, and it is logical to conclude that the only true primary ovarian neoplasms are germ cell and gonadal stromal tumors analogous to tumors in the testis. If this new model is confirmed, it has profound implications for the early detection and treatment of “ovarian cancer”.

Keywords Ovarian cancer – Pathogenesis – Model – Paradigm – Fallopian tube – Endometriosis – Serous tubal intraepithelial carcinoma – STIC – Serous carcinoma

(U.S.) Medscape: Feds Target Roles of PAs and Nurses for Comparative Research

Clinicians, patients, healthcare organizations, and the general public can weigh in on the proposed agenda and research priorities of PCORI at the agency's Web site or at its National Patient and Stakeholder Dialogue meeting, set for February 27 in Washington, DC. More information about the meeting is available at the PCORI Web site.

Jan 2012 abstract: Long-term follow-up of Jewish women with a BRCA1 and BRCA2 mutation who underwent population genetic screening

Blogger's Note: in this study longterm followup = 2 years

Abstract

There are two mutations in BRCA1 and one in BRCA2, which are present in up to 2.5% of Jewish women. Population genetic testing for Jewish women has been proposed; however, it is unclear how this would impact the uptake of cancer prevention options and psychosocial functioning in women with a positive result. Two thousand and eighty unselected Jewish women were tested for the Jewish BRCA mutations, and 1.1% were positive. Cancer-related distress was measured before testing, and at 1 and 2 years post-testing. Information on uptake of cancer risk reduction options was collected at 2 years. Breast and ovarian cancer risks were estimated using BRCAPRO. Within 2 years of receiving a positive result, 11.1% of women had prophylactic mastectomy, and 89.5% had a prophylactic oophorectomy. The mean breast cancer risk was estimated to be 37.2% at time of testing, compared to 20.9% at 2 years post-testing. The mean ovarian cancer risk was estimated to be 24.5% at time of testing, compared to 7.5% at 2 years following testing. Distress decreased between 1 and 2 years for women with prophylactic mastectomy and oophorectomy (P = 0.02), and for women with prophylactic oophorectomy only (P = 0.04) but not for those with neither surgery. The majority of Jewish women with a BRCA mutation identified through a population screening elected prophylactic oophorectomy, but a few had a prophylactic mastectomy. Uptake of either surgery resulted in decreased distress. Provision of population BRCA testing resulted in reduced risks of breast and ovarian cancers in women with a mutation.

Keywords  BRCA1 – BRCA2 – Breast cancer – Genetic testing – Jewish

BMC Cancer | Full text | Breast cancer patients with lobular cancer more commonly have a father than a mother diagnosed with cancer

Conclusion

We propose that lobular breast cancer is associated with having a father diagnosed with cancer, most commonly prostate carcinoma. Since the association remained after excluding family history of breast cancer, the association seems independent of classical breast cancer heredity. The association with a father diagnosed with cancer also remained after removing prostate cancer, indicating an independence from prostate cancer as well. The reason for this association is genetically unclear, but could involve sex-specific imprinting.

open access - BMC Cancer Laparoscopy to predict the result of primary cytoreductive surgery in advanced ovarian cancer patients (LapOvCa-trial): a multicentre randomized controlled study (protocol/design/Netherlands)

Study protocol

Laparoscopy to predict the result of primary cytoreductive surgery in advanced ovarian cancer patients (LapOvCa-trial): a multicentre randomized controlled study

BMC Cancer 2012, 12:31 doi:10.1186/1471-2407-12-31
Published: 20 January 2012

Abstract (provisional)

Background

Standard treatment of advanced ovarian cancer is surgery and chemotherapy. The goal of surgery is to remove all macroscopic tumour, as the amount of residual tumour is the most important prognostic factor for survival. When removal off all tumour is considered not feasible, neoadjuvant chemotherapy (NACT) in combination with interval debulking surgery (IDS) is performed. Current methods of staging are not always accurate in predicting surgical outcome, since approximately 40% of patients will have more than 1 cm residual tumour after primary debulking surgery (PDS). In this study we aim to assess whether adding laparoscopy to the diagnostic work-up of patients suspected of advanced ovarian carcinoma may prevent unsuccessful PDS for ovarian cancer.

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

BioMed Central Blog : Journal of Negative Results in Biomedicine

“Journal of Negative Results in Biomedicine's immediate goal is to provide scientists and physicians with responsible and balanced information in order to improve experimental designs and clinical decisions”, comments Prof Bjorn Olsen, Editor-in-Chief of this journal.
The importance and usefulness of negative results is something that is arguably overlooked in the scientific arena; they are often perceived as less important due to the fact that they fail to confirm various hypotheses. This view however is gradually changing, with a growing awareness of how constructive and useful they can actually be to science.
Journal of Negative Results in Biomedicine promotes the publication of negative results and data, and supports the idea that scientists should be provided with balanced information which can offer a more complete scientific record, thereby reducing the risk of publication bias or later rebuttal of research. Prof Olsen and JNRBM co-founder, Dr Christian Pfeffer, also strongly believe that “such "negative" observations and conclusions, based on rigorous experimentation and thorough documentation, ought to be published in order to be discussed, confirmed or refuted by others”.

Women Feel Pain More Intensely Than Men: Scientific American

"...But the study was large, and the findings are backed up by previous work, Fillingim said.
"I think the most [simple] explanation is that women are indeed experiencing higher levels of pain than men," Fillingim said.
The reason for this is not known, Fillingim said. Past research suggests a number of factors contribute to perceptions of pain level, including hormones, genetics and psychological factors, which may vary between men and women, Fillingim said. It's also possible the pain systems work differently in men and women, or women experience more severe forms of disease than men, he said."

Study examines research on overuse of health care services | e! Science News

"....However, the authors note the limited literature on overuse is understandable because of the challenges of developing standards to measure overuse.
"Expanding the evidence base and establishing appropriateness criteria for a broader range of services could help target and eliminate overuse in health care services, which could reduce health care spending without adversely affecting the health of the public," the authors conclude."

The Naked Doctor: profiling overdiagnosis and overtreatment

The Naked Doctor (blog): profiling overdiagnosis and overtreatment 

(eg. "Introducing the Naked Doctor: When is ‘no action’ the best action?")

Posted by Gary Schwitzer in Disease mongering, overtesting, overtreatment

Hot flash remedies: Estrogen may be the best answer - Health News Review

Hot flash remedies: Estrogen may be the best answer

Reviewed by Christine Norton, MA; Karen Carlson, MD; and Gary Schwitzer

Managing adult cancer pain: The latest NCCN guidelines - Chemotherapy Advisor

"Pain is common in cancer — one-third of patients undergoing treatment and three-fourths of those with advanced disease experience it — and pain is among the symptoms patients fear the most."

Integrating spiritual care as part of comprehensive cancer treatment - Chemotherapy Advisor

Benefits and risks of parenteral nutrition in patients with cancer - Chemotherapy Advisor

Using ESAs (erythropoietin-stimulating agents ) in patients with cancer-related anemia - Chemotherapy Advisor

Cancer Drug Monographs - Gynecologic Cancer Resource Center - Chemotherapy Advisor

Gynecological Cancer Drug Monographs

Gynecologic cancers
Adriamycin	Adriamycin Solution	Alkeran
Alkeran for Injection	Cosmegen	Doxil
Gemzar	Hexalen	Hycamtin
Hycamtin Capsules	Hydrea	Megace
Methotrexate for Injection	Methotrexate Injection	Paraplatin
Taxol	Trexall	Vinblastine for Injection
Vinblastine Injection
Data provided by the Monthly Prescribing Reference (MPR) Hematology/Oncology Edition.

FDA-Approved Ovarian Cancer Drug Treatments - Chemotherapy Advisor

Blogger's Note: webpage dated 2009

FDA-Approved Ovarian Cancer Drug Treatments - Chemotherapy Advisor

new website: Chemotherapy Advisor

Welcome to Chemotherapy Advisor, a new website that provides oncology professionals with practical resources such as cancer treatment regimens, concise drug monographs, updated oncology news, clinical charts and calculators, and much more.

open access: Jan 2012 Archives of Pathology & Laboratory Medicine Online - The Practice of Pathology in Canada: Decreasing Pathologist Supply and Uncertain Outcomes

Abstract (and full text):  

Context.—

Pathology organizations in the United States are preparing for a new era of health care reform. Trends in the supply of pathologists in Canada's managed care system may provide some useful insights in any analysis and projection of future pathologist needs in the United States.

Objective.—In this study, population-based Canadian databases were used to devise a parameter for physician supply, cancer cases per physician. The trend in this supply parameter for pathologists was compared to that for radiation oncologists.


Results.—
The annual number of new cancer cases increased from 129 300 to 171 000 from 1999 to 2009. The absolute numbers of both pathologists and oncologists also increased in this time period. However, while the increase in the number of radiation oncologists led to an 8.2% decrease in cancer cases per radiation oncologist, the modest increase in the number of pathologists led to an increase of 17.1% in cancer cases per pathologist.

Conclusions.—

There is a trend toward a decreasing supply of Canadian pathologists relative to that of cancer demands. This finding confirms an earlier population-based study showing a decreased supply relative to population and number of clinical physicians. It is uncertain whether this decreased supply is a result of appropriate application of new, efficient methods or whether health care has been rationed or adversely impacted. Outcome measures to monitor Canadian pathology practice quality are clearly needed.

open access: Archives of Pathology & Laboratory Medicine Online - Squamous Lesions of the Ovary

Defining:
Coelomic metaplasia is defined as some of the cells of the peritoneum (also known as the abdominal wall) developing into endometrial cells instead of normal peritoneal cells. Studies of pelvic peritoneal tissue from women undergoing laparotomy suggests that before endometriosis has become established in the peritoneum, there might be a metaplastic change by peritoneal mesothelial cells into endometrial glandular cells. In this article, we will discuss how coelomic metaplasia causes endometriosis.

Defining: Metaplasia:
....When cells are faced with physiological or pathological stresses, they respond by adapting in any of several ways, one of which is metaplasia......

--------------------------------------------------------------------------

Article:

"When encountered in the ovary, a diagnosis of squamous cell carcinoma can pose a challenging differential diagnosis. Although squamous cell carcinoma is a frequent entity encountered in the female genital tract, it is rare in primary form in the ovary and, hence, when identified therein, it is incumbent on the pathologist to explore other potential entities or primary sites. Primary squamous cell carcinoma has been identified in the ovary, however, and as such, demonstrates the vast histologic heterogeneity that may be seen in ovarian lesions. This is a review of the literature pertaining to ovarian squamous lesions, including a number of diagnostic pearls."

"COMMENT

Although squamous elements in the ovary are relatively common, squamous cell carcinoma is distinctly rare, especially in pure form. Debate continues on the pathogenesis of primary squamous cell carcinoma without an associated dermoid. Most authors suggest squamous cell carcinoma in association with endometriosis arises from neoplastic transformation of preexisting endometrial epithelium.7,11 This may be in keeping with the varied metaplasia and neoplasia that may be seen within endometrial glands. Cases of pure primary squamous cell carcinoma of the ovary are an even greater etiologic conundrum; some authors suggest that these lesions may arise because of seeding from occult premalignant or fully malignant squamous lesions located outside the ovary.7,11 These lesions may also serve as examples of the broad potential of coelomic metaplasia."

abstract: Interviews with patients with advanced cancer—another step towards an international cancer pain classification system - European Palliative

Conclusions

Previously identified pain domains were confirmed to be relevant to the patients; however, the ranking differed from the experts’ ranking. Sleep disturbances may be added as a domain in a future classification system.

media: Elderly and ill patients connect to their doctors via broadband: Pilot Australian project

abstract: The clinical effect of the dual-targeting strategy involving PI3K/AKT/mTOR and RAS/MEK/ERK pathways in patients with advanced cancer (phase 1)

Purpose: This study evaluated the clinical relevance of the dual-targeting strategy involving PI3K/AKT/mTOR and RAF/MEK/ERK pathways.

 P

Experimental Design: We investigated safety, efficacy and correlations between tumor genetic alterations and clinical benefit in 236 patients with advanced cancers treated with phase I study drugs targeting PI3K and/or MAPK pathways in our Phase I Clinical Trials Program.

abstract: Different perspectives on communication quality and emotional functioning during routine oncology consultations

Results

The patients’ ratings of communication quality differed significantly from those of both the physician and observer. Observer and physician scores did not differ significantly. Physicians rated emotional functioning as discussed more often than was reported from patient and observer perspectives.

Conclusion

The patients’ view of the quality of communication differed from that of the physician and observer. Whether emotional functioning was discussed or not was also perceived differently by patients, physicians, and observer.

press release: Group Settings Can Diminish Expressions of Intelligence ((fMRI))

Blogger's Note: note #6 in 'findings' section (gender related)

".....Research led by scientists at the Virginia Tech Carilion Research Institute found that small-group dynamics -- such as jury deliberations, collective bargaining sessions, and cocktail parties -- can alter the expression of IQ in some susceptible people. "You may joke about how committee meetings make you feel brain dead, but our findings suggest that they may make you act brain dead as well," said Read Montague, director of the Human Neuroimaging Laboratory and Computational Psychiatry Unit at the Virginia Tech Carilion Research Institute, who led the study."

media: The price of your soul: How the brain decides whether to 'sell out' (ethics/religion/money....)

"..."Our experiment found that the realm of the sacred – whether it's a strong religious belief, a national identity or a code of ethics – is a distinct cognitive process," says Gregory Berns, director of the Center for Neuropolicy at Emory University and lead author of the study. The results were published in Philosophical Transactions of the Royal Society.
Sacred values prompt greater activation of an area of the brain associated with rules-based, right-or-wrong thought processes, the study showed, as opposed to the regions linked to processing of costs-versus-benefits......"

press release: Scripps Research scientists provide new understanding of chronic pain (neuropathic pai

(In research)

Findings suggest new target for drug development

LA JOLLA, CA – January 22, 2012 – Millions of people worldwide suffer from a type of chronic pain called neuropathic pain, which is triggered by nerve damage. Precisely how this pain persists has been a mystery, and current treatments are largely ineffective. But a team led by scientists from The Scripps Research Institute, using a new approach known as metabolomics, has now discovered a major clue: dimethylsphingosine (DMS), a small-molecule byproduct of cellular membranes in the nervous system. In their new study, the scientists found that DMS is produced at abnormally high levels in the spinal cords of rats with neuropathic pain and appears to cause pain when injected. The findings suggest inhibiting this molecule may be a fruitful target for drug development.....

New Genetic Clues to Breast Cancer? - Drugs.com MedNews

SUNDAY Jan. 22, 2012 --
"Researchers have identified three new genomic regions they believe are linked with breast cancer that may help explain why some women develop the disease..........Scientists conducting genome-wide association studies -- research that looks at the association between genetic factors and disease to pinpoint possible causes -- had already identified 22 breast cancer susceptibility loci. Locus is the physical location of a gene or DNA sequence on a chromosome. "The three [newly identified] loci take the number of common susceptibility loci from 22 to 25," said Easton. However, the three new susceptibility loci might explain only about 0.7 percent of the familial risks of breast cancer, bringing the total contribution to about 9 percent, the researchers said.'".......

Who Owns Data From Inside Your Body? - On The Media (text/audio)

Vaccines to boost immunity where it counts, not just near shot site | e! Science News

"It should not be long because all the individual cytokines (immune system factors) and additional materials loaded into these particles are already FDA approved for use in humans," Abraham said. "There is a lot of interest in nanoparticle-based therapy, but we are basing our materials on our observation of mast cells in nature. This is an informed application to deliver the right material to the right place in the body to get the most effective immune reaction."

Vote: Should Patients Have Electronic Identification Numbers? - Health Blog - WSJ

no abstract: Is comprehensive surgical staging needed for thorough evaluation of early stage ovarian carcinoma? (Journal Club article for discussion March 2012

Blogger's Note: requires subscription ($$$)
 ..................................................................
references original article:

Is comprehensive surgical staging needed for thorough evaluation of early-stage ovarian carcinoma?

• Conclusion

  Patients with epithelial ovarian cancer should continue to undergo comprehensive surgical staging, since it identifies occult metastasis in a significant number of patients.

   Available online 22 August 2011.

abstract: Association of death receptor 4 variant (683A>C) with ovarian cancer risk in BRCA1 mutation carriers.

abstract: Recommendations on management of EGFR inhibitor-induced skin toxicity: A systematic review

"Due to the small number of randomized controlled trials conducted in the field of EGFR inhibitor-induced skin toxicity so far, it is not possible yet to generate evidence based guidelines on its management. Here, we review and discuss ($$$ requires subscription) available trials and case studies reporting on the management of EGFR inhibitor-induced skin toxicity."

abstract: Profiling clinical cancer research across the Atlantic: A review of research and its characteristics presented at ASCO and ESMO Congresses during the last decade

Conclusions

Cancer clinical research is a complex scientific activity with common global but also distinct characteristics at the two sides of the Atlantic.

Keywords

• Clinical research;
• Trials;
• Oncology Congresses;
• ASCO;
• ESMO

ASCO 2011 abstract: A North American population-based outcome for early-stage ovarian clear cell (stages 1-11) carcinoma (OCCC). - ASCO 2011 (including w/wo irradiation)

Abstract:

Background: OCCC is regarded as having a poor outcome and being relatively treatment resistant. Recent Japanese data instead have demonstrated high survival in early stage and radiation sensitivity. This study was carried out to reproduce/refute these findings in a North American setting.

Methods: Women with OCCC who had attended one of the four British Columbia Cancer Agency (BCCA) centers have staging, pathological, treatment, and outcome data recorded in a computerized database. Irradiation (XRT) plus platin-based chemotherapy was the standard treatment. XRT usage mandated all such women provincially attending a BCCA centre. However, individual physicians within BCCA differed in their uptake of XRT. Outcomes with or without XRT could be compared. Univariate and multivariate (decision-tree analysis) analyses for disease-free survival (DFS) were performed.

Results: 241 Stage I-II women attended between January 2000 and December 2008 (IA/IB n=64; Ic n=147; II n=30). 5 year and 10 year DFS for stage IA/B; IC and II were 85 and 70%; 64 and 58%; and 43 and 43% respectively. IC subsets faired differently: rupture alone (spontaneous and surgical were equivalent) - 5 yr DFS 80% versus 34% if cytologically positive and 43% with surface involvement. Decision-tree analysis identified cytologic positivity as the most important factor (recurrence 27% if negative, 72% if positive). Surface involvement then further subdivided the cytologically positive: surface involved 93% recurrence, if not involved 60%. XRT had no effect in stage IA (85% DFS at 5 yrs with or without it) but was superior to chemotherapy alone in IC (5 yr DFS 68% vs 58%, 10 yr DFS 63% vs 52%, HR 0.59).
Conclusions: Stage IA OCCC has an excellent long-term outcome as does IC (rupture only). IC otherwise has a poor outcome as does stage II. XRT and chemotherapy improves outcome in stage IC versus chemotherapy alone.

New York Times - News Analysis - "I Disclose ... Nothing" (patient safety communities ??)

"........One fundamental problem is that disclosure requirements merely get information onto the table, but themselves demand no further action. According to political theory, disclosure is both a citizen’s right and a tool to ensure good government and consumer protection, because it provides information that leads to informed decisions. Instead, disclosure has often become an endpoint in the chain of responsibility, an act of compliance with the letter of the law rather than the spirit of transparency....."

"“In the beginning, disclosure was a means to an end, and now it’s often an end in itself,” said Kevin P. Weinfurt, professor of psychiatry and behavioral science at Duke University. “People think, ‘If we’ve disclosed we’ve fulfilled our responsibilities.’ ”

abstract: Natural history and outcome of mucinous carcinoma of the ovary (women dx'd 1988 to 2007)

Blogger's Note: this conclusion therefore begs an obvious question

OBJECTIVE:

We performed a population-based analysis to compare the clinical characteristics of women with mucinous tumors with women with other epithelial tumors. (SEER stats)

 CONCLUSION:

Although survival for early-stage mucinous and serous tumors is similar, survival for advanced-stage mucinous neoplasms is inferior to that of serous carcinomas.

abstract: Am J Clin Pathology - Value of PAX8 and WT1 Immunostaining in Confirming the Ovarian Origin of Metastatic Carcinoma in Serous Effusion Specimens.(note reference to clear cell ovarian/malignant effusion)

Am J Clin Pathol. 2012 Feb;137(2):304-9.

Value of PAX8 and WT1 Immunostaining in Confirming the Ovarian Origin of Metastatic Carcinoma in Serous Effusion Specimens.

Abstract

We evaluated the detection rates of PAX8 and WT1 immunostaining in 68 (45 as cell blocks, 23 as smears) serous effusion specimens that had a cytologic diagnosis of metastatic carcinoma of ovarian origin. Of the cases, 58 (85%) were positive for PAX8, 56 (82%) were positive for WT1, and 64 (94%) were immunoreactive with either or both markers.

Detection rates of PAX8 and WT1 were 85% (44/52) and 92% (48/52), respectively, for metastatic serous carcinoma and 100% (5/5) and 20% (1/5), respectively, for metastatic clear cell carcinoma (Blogger's note: small sample size in clear cell).

Detection rates using cell blocks and smears were 91% and 78%, respectively, with PAX8 and 82% and 83%, respectively, with WT1.

We concluded that PAX8 and WT1 had comparable overall detection rates in confirming ovarian origin of malignant effusion. The combination of both markers substantially improved the detection rate. Cell blocks and smears can be used for staining, but a cell block is preferred for PAX8 staining.

open access: Review - 2010 Targeted Therapies in Epithelial Ovarian Cancer

Review

Targeted Therapies in Epithelial Ovarian Cancer

Download PDF Full-Text

Abstract:

Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the advantage of long-term therapy with a manageable toxicity profile enabling patients to enjoy a good quality of life.

In this review we appraise the emerging data on novel targeted therapies in ovarian cancer. We discuss the role of these compounds in the front-line treatment of ovarian cancer and in relapsed disease; and describe how the development of predictive clinical, molecular and imaging biomarkers will define the role of biological agents in the treatment of ovarian cancer.

abstract: A survey of the perspectives of patients who are seriously ill regarding end-of-life decisions in some medical institutions of Korea, China and Japan

Purpose
"The debate about the end-of-life care decision is becoming a serious ethical and legal concern in the Far-Eastern countries of Korea, China and Japan. However, the issues regarding end-of-life care will reflect the cultural background, current medical practices and socioeconomic conditions of the countries, which are different from Western countries and between each other. Understanding the genuine thoughts of patients who are critically ill is the first step in confronting the issues, and a comparative descriptive study of these perspectives was conducted by collaboration between researchers in all three countries....."

abstract: Reframing eating during chemotherapy in cancer patients with chemosensory alterations

Purpose

Our purpose was to describe how eating is reframed among cancer patients experiencing chemosensory alterations.

Conclusion

To date, interventions to promote eating among cancer patients have focused extensively on symptom management and on recommendations for macro/micronutrient intake. This study underscores the importance of understanding beliefs about eating. These beliefs may help clinicians develop patient-centered nutritional interventions.

Seth's Blog: Insatiable

abstract: Acute Abdominal Venous Thromboses-The Hyperdense CT Sign (blood clots)

CONCLUSION:

Acute abdominal VT (acute abdominal venous thrombosis) can be detected on unenhanced CT in more than two thirds of the cases by identifying hyperdense venous segments.

abstract: Anthropometric Measures (BMI, height, weight gain) and Risk of Ovarian Cancer Among BRCA1 and BRCA2 Mutation Carriers

"....Height, weight, and BMI were not associated with the risk of ovarian cancer (P-trend ≥0.15). Also, there was no association between changes in body weight between ages 18-30, or ages 30-40, or ages 18-40 and the risk of ovarian cancer (P-trend ≥0.28). The results from this study suggest that height, weight, or weight gain do not influence the risk of ovarian cancer among carriers of a BRCA1 or BRCA2 mutation."

abstract: Percutaneous Insertion of (IP) Peritoneal Ports (study = 29 women)

Objective: To describe a technique for image-guided percutaneous insertion of peritoneal ports in patients without ascites who have undergone surgical debulking for stage III ovarian cancer.

Conclusions: Placement of percutaneous intraperitoneal ports is feasible with an acceptably low complication rate of 6.9% in patients without abdominal ascites.

abstract: Significance of Perioperative Infection in Survival of Patients With Ovarian Cancer

Objectives:
Perioperative infectious diseases comprise some of the most common causes of surgical mortality in women with ovarian cancer. This study was aimed to evaluate the significance of perioperative infections in survival of patients with ovarian cancer.

Conclusion:

Perioperative infectious disease comprises an independent risk factor for survival of patients with ovarian cancer.

"Perioperative infections were associated with increased surgical mortality, delay in chemotherapy treatment, decreased chemotherapy response, shorter progression-free survival) and decreased overall survival ." (Blogger's note - stats removed for ease of reading)

abstract: Extraperitoneal metastases from recurrent ovarian cancer. (study n=233 women) eg. lung, CNS, pulmonary, skin (cutaneous)

Blogger's note: requires subscription ($$$) for full text

OBJECTIVES:

To identify patterns of metastasis in patients with recurrent ovarian cancer. The influence of the route of chemotherapy administration and sequence of agents on those patterns is also examined.

RESULTS:

Thirty-five subjects developed extraperitoneal recurrent ovarian cancer, with 26 subjects (74%) after IP treatment, and 9 subjects (26%) after IV treatment. Of these extraperitoneal recurrences, 26 were in the thoracic/pulmonary cavity, 7 were within the central nervous system (CNS), and 2 were in the cutaneous (skin) tissues. The CNS and cutaneous lesions were secondary recurrences, and all occurred in subjects who had initially received IP cisplatin/paclitaxel followed by IV BEV for recurrent disease.

CONCLUSIONS:

Extraperitoneal recurrences were more common in women treated with IP chemotherapy for ovarian cancer. Specifically, women treated with IV BEV as secondary therapy after IP were at particularly high risk of extraperitoneal metastases, including in the CNS and cutaneous tissues. Physicians should be aware of the possibility of unusual metastases after the combination of IP chemotherapy and BEV, and future prospective studies of this population should carefully evaluate recurrence site patterns.

open access - Genes: Modeling the Risk of Secondary Malignancies after Radiotherapy

Blogger's Note: it is important to keep the issue of treatment-related secondary malignancies in context ** (eg. longterm survival; chemotherapy-related secondary malignancies, risk factors such as genetic syndromes eg. Lynch Syndrome; research seems to indicate that most of the Chernobyl related cancers have been thyroid cancers. 

** ("Certain chemotherapeutic agents, particularly alkylating agents and topoisomerase II inhibitors, increase the risk of developing a second cancer.")

 ....................................................................................................

Genes 2011, 2(4), 1033-1049; doi:10.3390/genes2041033

Review

(This article belongs to the Special Issue Radiation-Related Cancer 25 Years After Chernobyl)

Download PDF Full-Text

Abstract:

In developed countries, more than half of all cancer patients receive radiotherapy at some stage in the management of their disease. However, a radiation-induced secondary malignancy can be the price of success if the primary cancer is cured or at least controlled. Therefore, there is increasing concern regarding radiation-related second cancer risks in long-term radiotherapy survivors and a corresponding need to be able to predict cancer risks at high radiation doses. Of particular interest are second cancer risk estimates for new radiation treatment modalities such as intensity modulated radiotherapy, intensity modulated arc-therapy, proton and heavy ion radiotherapy. The long term risks from such modern radiotherapy treatment techniques have not yet been determined and are unlikely to become apparent for many years, due to the long latency time for solid tumor induction. Most information on the dose-response of radiation-induced cancer is derived from data on the A-bomb survivors who were exposed to γ-rays and neutrons. Since, for radiation protection purposes, the dose span of main interest is between zero and one Gy, the analysis of the A-bomb survivors is usually focused on this range. With increasing cure rates, estimates of cancer risk for doses larger than one Gy are becoming more important for radiotherapy patients. Therefore in this review, emphasis was placed on doses relevant for radiotherapy with respect to radiation induced solid cancer. Simple radiation protection models should be used only with extreme care for risk estimates in radiotherapy, since they are developed exclusively for low dose. When applied to scatter radiation, such models can predict only a fraction of observed second malignancies. Better semi-empirical models include the effect of dose fractionation and represent the dose-response relationships more accurately. The involved uncertainties are still huge for most of the organs and tissues. A major reason for this is that the underlying processes of the induction of carcinoma and sarcoma are not well known. Most uncertainties are related to the time patterns of cancer induction, the population specific dependencies and to the organ specific cancer induction rates. For radiotherapy treatment plan optimization these factors are irrelevant, as a treatment plan comparison is performed for a patient of specific age, sex, etc. If a treatment plan is compared relative to another one only the shape of the dose-response curve (the so called risk-equivalent dose) is of importance and errors can be minimized.
.........................................................................

(Tinnitus ) Ringing in Your Ears? - NIH News in Health (general, not specific to treatment-related side effect)

abstract: Pre-Treatment Tumor Expression of ERCC1 in Women with Advanced Stage Epithelial Ovarian Cancer is Not Predictive of Clinical Outcomes: A GOG study

Conclusions

ERCC1 expression, measured by IHC in pre-treatment tumor specimens, using a highly specific antibody, has limited clinical value in patients with advanced EOC treated with platinum and taxane based chemotherapy.

---

Highlights

► ERCC1 tumor expression in advanced EOC is not associated with patient survival.
► Common polymorphisms in ERCC1 were not associated with ERCC1 immunohistochemical expression.

Jan 20th: open access: Journal of Ovarian Research IGFBP-4 tumor and serum levels are increased across all stages of epithelial ovarian cancer - papillary serous tumors; note reference to Hispanic women (Italy/US study)

Background (pdf file)
"Epithelial Ovarian Cancer (EOC) is the most lethal female reproductive tract malignancy with nearly 200,000 new cases and >125,000 deaths attributable to the disease each year worldwide (1).........The search for reliable, specific, and sensitive serum-based biomarkers for EOC
has a long history and its major highlight remains the identification of CA125 nearly 30 years ago (4)."

"Papillary serous tumor samples were collected across all stages (five stage I/II, 11 stage III/IV, two disseminated peritoneal lesions, and two recurrent tumors). For comparison, two borderline tumors were also sequenced."

Research

IGFBP-4 tumor and serum levels are increased across all stages of epithelial ovarian cancer.

Journal of Ovarian Research 2012, 5:3 doi:10.1186/1757-2215-5-3
Published: 20 January 2012

Abstract (provisional)

Background

We sought to identify candidate serum biomarkers for the detection and surveillance of EOC. Based on RNA-Seq transcriptome analysis of patient-derived tumors, highly expressed secreted proteins were identified using a bioinformatic approach.

Methods

RNA-Seq was used to quantify papillary serous ovarian cancer transcriptomes.......... Serum samples from women with benign and malignant pelvic masses and serial samples from women during chemotherapy regimens were measured for IGFBP-4 by ELISA.....

Results

Insulin-like growth factor binding protein (IGFBP-4) was consistently present in the top 7.5% of all expressed genes in all tumor samples. We then screened serum samples to determine if increased tumor expression correlated with serum expression. In an initial discovery set of 21 samples, IGFBP-4 levels were found to be elevated in patients, including those with early stage disease and normal CA125 levels. In a larger and independent validation set (82 controls, 78 cases), IGFBP-4 levels were significantly increased (p<5x10-5). IGFBP-4 levels were ~3x greater in women with malignant pelvic masses compared to women with benign masses. ROC sensitivity was 73% at 93% specificity (AUC 0.816). In women receiving chemotherapy, average IGFBP-4 levels were below the ROC-determined threshold and lower in NED patients compared to AWD patients.

Conclusions

This study, the first to our knowledge to use RNA-Seq for biomarker discovery, identified IGFBP-4 as overexpressed in ovarian cancer patients.  

Beyond this, these studies identified two additional intriguing findings. First, IGFBP-4 can be elevated in early stage disease without elevated CA125. Second, IGFBP-4 levels are significantly elevated with malignant versus benign disease. These findings provide the rationale for future validation studies. 

pdf: 
Future studies are planned primarily to increase sample size and diversity of patients. Unexpectedly, we noted that Hispanic cases have significantly higher serum IGFPB-4 levels compared to other non-Hispanic cases or all controls . We are unaware of previous reports or studies suggesting a biologic basis for this finding. Thus, this intriguing finding will be specifically explored in future studies.

--------------------------------------------------------------

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

Norway Launches National Cancer Genomic Medicine Effort | GenomeWeb

Blogger's Note: requires registration to view (free)

NEW YORK (GenomeWeb News) – "Norway has kicked off a national collaborative effort to use deep sequencing to discover and use genetic mutations for treating cancer patients and to create a program for using genomic medicine in the clinic...."

Ototoxic Medications - (damage to the ear eg. chemotherapy-induced tinnitus)

From Wikipedia, the free encyclopedia:

Ototoxicity is damage to the ear (oto-), specifically the cochlea or auditory nerve and sometimes the vestibular system, by a toxin. It is commonly medication-induced; ototoxic drugs include antibiotics such as the aminoglycoside gentamicin, loop diuretics such as furosemide, and platinum-based chemotherapy agents such as cisplatin. A number of nonsteroidal anti-inflammatory drugs (NSAIDS) such as Meloxicam have also been shown to be ototoxic. This can result in sensorineural hearing loss, dysequilibrium, or both. Either may be reversible and temporary, or irreversible and permanent.
.............................................................................

		Ototoxic Medications Timothy C. Hain, MD Page last modified: December 25, 2011 Chemotherapy Agents Antibiotics With Good Evidence for Ototoxicity Antibiotics for Which There is Some Suspicion of Ototoxicity Antibiotics Generally Considered Safe Ototoxic Diuretics Quinine Derivatives Aspirin and related medications Miscellaneous Ototoxic Drugs Other Toxins Protection   The purpose of this page is to list drugs well known to be toxic to the ear. It is not all-inclusive and it should not be relied upon for medical care.

UH Case Medical Center Offers New Therapy (HIPEC) for Gynecologic Cancer Patients -- CLEVELAND, Jan. 20, 2012 /PRNewswire/

CLEVELAND, Jan. 20, 2012 /PRNewswire/ -- Patients with gynecologic cancer have new hope in a novel technology now offered at the Seidman Cancer Center at University Hospitals (UH) Case Medical Center. A team of cancer specialists, led by Robert DeBernardo, MD, is among the first in the nation to launch a dedicated program using Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to treat ovarian, endometrial and select other cancers....."

American Cancer Society: Holistic Medicine

Office of Dietary Supplements (ODS) - NIH

Clinical Oncology News - Circulating Tumor Cells: The Ultimate Assay?

".....But simply being able to predict who will do better and who will do worse is of little value to the patient, other than knowing who needs to get their affairs in order more quickly. Clinical utility depends on actually being able to shape treatment choices based on the information provided in an assay.
Can CTCs do that? Maybe....."

Commentary to article Gilbert (Dove Project) - Early detection of ovarian cancer in symptomatic women : The Lancet Oncology

The Lancet Oncology, Early Online Publication, 17 January 2012

doi:10.1016/S1470-2045(11)70405-3

Early detection of ovarian cancer in symptomatic women

JR van Nagell a

"Since Goff and co-workers1 first reported that many women with ovarian cancer have symptoms of abdominal bloating, early satiety, pelvic pain, and urinary urgency, frequency, or both, questions have arisen as to whether assessment of these symptoms could lead to earlier detection of this cancer. The Diagnosing Ovarian Cancer Early (DOvE) pilot project reported in The Lancet Oncology by Gilbert and co-workers2 seeks to answer this question. Clinical examination, measurement of CA-125 concentrations in serum, and transvaginal ultrasonography (TVUS) were used in 1455 women older than 50 years who had symptoms associated with ovarian cancer. 11 ovarian cancers were detected, which yielded a prevalence of one per 132 women (0·76%), or about ten times that observed in screening studies in the USA, UK, and Japan.3—5."

"Whether assessment of symptomatic women with multiple methods will lead to detection at earlier stages or increase survival needs to be tested in larger numbers of cases. That the assessment algorithm used in the DOvE project identified most patients with symptomatic ovarian cancer when their disease was still resectable, however, is encouraging. Optimum cytoreduction is associated with a notable survival advantage in patients with ovarian cancer, and was achieved in eight (73%) of 11 women in the study group versus 33 (44%) of 75 women in a control group of patients with ovarian cancer who had been referred to a local gynaecological oncology clinic (p=0·075). The degree of cytoreduction, however, also depends on factors other than tumour burden, including the location of disease and experience of the surgeon. To continue this project beyond the pilot phase, it will be important to document disease substage and note tumour volume before debulking (in study and control cases) to establish whether assessment-driven interventions affect tumour burden. Although the DOvE algorithm successfully identified 11 cases of ovarian cancer, 1444 (99.2%) symptomatic women did not have ovarian cancer. In the next phase of this study, the positive and negative predictive values of each symptom must be critically assessed to identify the profile of highest risk. Additionally, the duration of symptoms before ovarian cancer detection should be recorded for the study and control populations. In this way, it should be possible to investigate whether a public education campaign alters the time from symptom onset to detection of disease in patients with ovarian cancer."
..................................................................................................................

Assessment of symptomatic women for early diagnosis of ovarian cancer: results from the prospective DOvE pilot project

Prof Lucy Gilbert MD et al

Cochrane Syst Review (abstract) 2012 Jan 18 Robotic assisted surgery for gynaecological cancer.

 

BACKGROUND:

Robotic surgery is the latest innovation in the field of minimally invasive surgery. Robotic surgical systems have been used to perform surgery for endometrial, cervical cancer and ovarian cancer. There is mounting evidence which demonstrates the feasibility and safety of robotic surgery for gynaecological oncology.

 MAIN RESULTS:

No studies were found that met the inclusion criteria. Controlled clinical trials (CCTs) are summarised and analysed, but are not discussed in the main body of the review as they present a high risk of bias.

Stein Kaasa (Norway): Let me show you what integrated palliative care can do - Cover Story - Issues 46 - Articles - Cancer World (open access)

"One aspect of his field particularly annoys Kaasa, and that is terminology. As far as he is concerned, it is called ‘palliative care’ or ‘palliative medicine’ and should cover the vast majority of the advanced cancer journey. But he says confusion can be spread by the use of ‘end of life care’ and ‘supportive care’. “In some cancer centres this is often about competing for resources, with some focusing on what they call earlier symptom control in ‘supportive care’, while leaving others to do the ‘end of life’. Yes, if you have a large palliative care team you can have people focusing more on early symptoms, but really this is often about a resources battle and not integrated care, and of course again it is the patients who fall into the gaps.”"

open access: Cancer in Australia: Actual incidence and mortality data from 1982 to 2007 and projections to 2010 - 2011 - Asia-Pacific Journal of Clinical Oncology - Wiley Online Library

Cancer in Australia: Actual incidence and mortality data from 1982 to 2007 and projections to 2010 - 2011 - Asia-Pacific Journal of Clinical Oncology

 Table 1.  The 10 most commonly diagnosed cancers by sex, Australia, 2007 

 Ovary    1,266

Table 4.  The 10 most common causes of death from cancer by sex, Australia, 2007 

Ovary      848


About this Journal:
The Asia-Pacific Journal of Clinical Oncology is a multidisciplinary journal of oncology that aims to be a forum for facilitating collaboration and exchanging information on what is happening in different countries of the Asia Pacific region in relation to cancer treatment and care. The Journal publishes pre-clinical studies, translational research, clinical trials and epidemiological studies, describing new findings of clinical significance. Clinical studies, particularly prospectively designed clinical trials, are encouraged.

Patients need information. Is that clear? - Editorial - Issues 43 - Articles - Cancer World including commentaries

Luzia Travado: improving outcomes for patients by attending to their distress - Cover Story - Issues 45 - Articles - Cancer World

(Psycho-oncology)

“Psychosocial burdens can be more threatening in many cases than the disease itself,” says Travado. “Even when a cancer is treatable someone may feel in despair and not cope. What we need to impress on policy makers and the medical community is that we are part of the frontline team and not a separate department dealing with a different part of a patient.”

website- Cancer World - Education & knowledge through people & facts (free subscription)

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2012 conference - WORLD ONCOLOGY FORUM- ESO: 26-27 October 2012, Lugano, Switzerland "Are We Winning the War on Cancer?"

WORLD ONCOLOGY FORUM®

Are We Winning the War on Cancer?
1 Question • 100 Experts • 1 Answer
26-27 October 2012, Lugano, Switzerland

Hosted by ESO Founders: Laudomia Del Drago and Umberto Veronesi
Chaired by: Franco Cavalli
ESO WOF Scientific Coordinator: Kathy Redmond

In partnership with The Lancet and Cancer World

5th Familial Cancer Conference - Event - ESO 07/06/2012 - 08/06/2012, Madrid, Spain

LEARNING OBJECTIVES

• To update recent advances in familial cancer
• To better define the genetic profile of these cancers and the clinical management of families and patients.
• To analyze the impact of the new technologies and their contribution to familial cancer risk.MAIN TOPICS

• General concepts in familial cancer: genetic variants, variants of unknown significance; modifier factors; genetic counseling
• Common cancers: breast cancer and the family of breast cancer genes; selection criteria and clinical management; new treatments; colorectal cancer and prostate cancer; genetic and clinical management.
• Other hereditary syndromes: Familial pheocromocitoma; pancreatic cancer; Birt-Hogg-Dube syndrome; familial melanoma.
• Rare tumors: Fanconi anemia; Dysqueratosis congenital; genetic syndromes of the RAS/MAP pathway; li Fraumeni syndrome.
• New technologies applied to familial cancer studies: Integrative genomic analysis; cancer genome and personalized medicine; whole exome sequencing in the search of high susceptibility genes. 

CONFIRMATION OF REGISTRATION

Registration may be carried out online (www.cnio.es/meetings). 

Registration fee is € 200. Registration and payment must be processed by 15 May 2012. After this date registration will only be available on site at the rate of € 300. The registration fee covers admission to the conference, a copy of the programme book, coffee and lunch throughout the conference as indicated in the programme. 

Personalized Medicine Coalition - website + newsletter Winter 2012 Coalition

PMC Newsletter:

Current Issue - Winter 2012

PLoS ONE: Lack of Effect of Lowering LDL Cholesterol on Cancer: Meta-Analysis of Individual Data from 175,000 People in 27 Randomised Trials of Statin Therapy

Blogger's Note: Table S1 does not specifically show gyn/ovarian cancers unless they have been reported in 'other' or 'unspecified'; a search of the document for 'gyn'/'ovarian'/'ovary' did not provide a result

Background

Statin therapy reduces the risk of occlusive vascular events, but uncertainty remains about potential effects on cancer. We sought to provide a detailed assessment of any effects on cancer of lowering LDL cholesterol (LDL-C) with a statin using individual patient records from 175,000 patients in 27 large-scale statin trials.


Table S1.
Number of patients with a report of cancer (number of cancer deaths), by site and trial.
(PDF)

Conclusion

"........ The present report now demonstrates clearly that such reductions in LDL cholesterol do not increase the rate of cancer or cancer death, overall or at any particular site, during a treatment period of about 5 years (and more prolonged follow-up in some of the trials does not indicate any later excess) even among older individuals or those who have their cholesterol levels reduced to very low levels. These findings provide considerable reassurance about the safety of using more intensive statin regimens to lower LDL cholesterol levels substantially in patients who remain at high risk of major vascular events."