OVARIAN CANCER and US

abstract: Identification of Cancer Patients with Lynch Syndrome: Clinically Significant Discordances and Problems in Tissue-Based Mismatch Repair Testing

2012-01-28T15:44:00.000-05:00

"In summary, concordance between immunohistochemistry and MSI was high, particularly for tumors that are microsatellite stable. Greater frequency of test discordance was identified in the tumors that were MSI-high. Thus, a major consequence of the use of immunohistochemistry by itself as a screen is the failure to identify colorectal and endometrial cancer patients who likely have Lynch syndrome. Cancer Prev Res; 5(2); 1–8. ©2011 AACR.

abstract: Hereditary colorectal cancer diagnostics: morphological features of familial colorectal cancer type X versus Lynch syndrome

2012-01-28T15:28:00.002-05:00

Hereditary colorectal cancer diagnostics: morphological features of familial colorectal cancer type X versus Lynch syndrome:

Background
The hereditary non-polyposis colorectal cancer (HNPCC) subset of tumours can broadly be divided into tumours caused by an underlying mismatch-repair gene mutation, referred to as Lynch syndrome, and those that develop in families with similar patterns of heredity but without disease-predisposing germline mismatch repair mutations, referred to as familial colorectal cancer type X (FCCTX). Recognition of HNPCC-associated colorectal cancers is central since surveillance programmes effectively reduce morbidity and mortality. The characteristic morphological features linked to Lynch syndrome can aid in the identification of this subset, whereas the possibility to use morphological features as an indicator of FCCTX is uncertain.

Objective and methods
To perform a detailed morphological evaluation of HNPCC-associated colorectal cancers and demonstrate significant differences between tumours associated with FCCTX and Lynch syndrome.

Results
The morphological features associated with Lynch syndrome, that is, right-sided tumour location, poor differentiation, expansive growth pattern, tumour-infiltrating lymphocytes, peritumorous lymphocytes, Crohn-like reactions, and lack of dirty necrosis, were significantly less often observed in FCCTX tumours.

Discussion
The less typical morphology in FCCTX implies that family history of cancer needs to be taken into account since these tumours cannot readily be recognised based on histopathological features.

abstract: Psychological impact of recall on women with BRCA mutations undergoing MRI surveillance

2012-01-28T12:46:00.001-05:00

CONCLUSIONS:

While breast MRI surveillance did not have a detrimental psychological impact on women with a BRCA1 or BRCA2 mutation, recalling these very high-risk women for further imaging after a false positive MRI scan temporarily increased their global anxiety.

abstract: Prognostic Value of Biomarkers Related to Drug Resistance in Patients with Advanced Epithelial Ovarian Cancer

2012-01-28T12:38:00.001-05:00

Prognostic Value of Biomarkers Related to Drug Resistance in Patients with Advanced Epithelial Ovarian Cancer:

Background/Aim:
We aimed to investigate the prognostic value of biomarkers [Ki-67, adenosine triphosphate-binding cassette sub-family B member 1 (ABCB1), adenosine triphosphate-binding cassette sub-family C member 1 (ABCC1), adenosine triphosphate-binding cassette sub-family C member 2 (ABCC2), p53, cyclin E and v-akt murine thymoma viral oncogene homolog 2 (AKT2)] in patients with advanced epithelial ovarian cancer (EOC).

Materials and Methods:
The levels of expression of biomarkers in tumor tissues of 47 patients with stage 3 or 4 EOC were estimated via immunohistochemical staining using tissue microarrays. The associations of biomarker expression with progression-free survival (PFS) and overall survival (OS) were evaluated using a log-rank test and Cox regression analysis.

Results:
Based on multivariate analysis, high expression of Ki-67 (p=0.003) and low expression of ABCC2 (p=0.048) were associated with a prolonged PFS. However, other biomarkers were not associated with PFS. Residual tumor <1 cm (p=0.023) and PFS >6 months (p=0.005) were associated with prolonged OS. However, none of the biomarkers were associated with OS.

Conclusion: High expression of Ki-67 and low expression of ABCC2 appear to be useful as markers for prolonged PFS in patients with advanced EOC.

abstract: Tumor Interstitial Fluid as Modulator of Cancer Inflammation, Thrombosis, Immunity and Angiogenesis

2012-01-28T12:28:00.001-05:00

Tumor Interstitial Fluid as Modulator of Cancer Inflammation, Thrombosis, Immunity and Angiogenesis:
Tumor interstitial fluid (TIF) is a watery phase that accumulates inside the tumor interstitium. Its genesis and fate depend on various factors, namely tumor type, metabolic state of the tumor, expression of vascular endothelial growth factor, and absence of lymphatic system. For almost 30 years TIF remained a neglected entity until it was demonstrated that TIF, and in particular its high pressure, constitutes an important obstacle to drug delivery and immunotherapy. The present review not only summarizes the abundant literature on the processes of TIF genesis and on its effects on therapy but it also presents data that, in our opinion, point towards what is perhaps the real physiological purpose of TIF: a primitive means of providing nourishment, oxygen, cytokines and matrikines to tumor cells that furthermore promotes the invasion of the normal surrounding tissue and passive metastatization through lymphatics. It is also an inducer of inflammation through increased osmolarity due to albumin loss. Recently, a role for TIF as a possible source of biomarkers has also been suggested.

Clinical Oncology News - Triple-Negative Breast Cancers Associated With Ashkenazi Origin

2012-01-28T07:39:00.001-05:00

Clinical Oncology News (ethics) - Would You Be ‘Surprised’: "The Surprise Question" (prognosis)

2012-01-28T07:36:00.001-05:00

The Surprise Question

"We turn to the problem of uncertainty and its impact on providing information. Recently, investigators have studied the “surprise” question, an interesting approach to making better survival predictions. The approach is somewhat ironic because although the question is subjective in nature, it tends to produce a good objective response. When physicians are asked to judge survival time, they tend to be inaccurate even when using the best prognostication information, including comorbidities, staging, advance directive status and whether the cancer has metastasized.

However, a recent study revealed that physicians are more accurate when they answer the surprise question: “Would I be surprised if this patient died in the next year?” A negative answer indicates an expectation of death within a year, whereas an affirmative answer indicates the physician’s gut response that the patient is highly likely to be alive within a year.¹ In a study of 826 cancer patients, an affirmative answer proved “correct” in 97% of the responses; almost all of the patients with a “yes” response to the question were alive within a year......"

Comparing Poly (ADP–Ribose) Polymerase Inhibitors With Standard Chemotherapy in BRCA-Mutated, Recurrent Ovarian Cancer: Lessons Learned From a Negative Trial (Olaparib)

2012-01-28T07:20:00.001-05:00

"...Thus, although the study by Kaye et al¹¹ does not show a clear advantage of olaparib compared with PLD, it is noteworthy for what it teaches us about the difficulties in performing and interpreting the results of randomized trials that involve this promising class of new agents in patients with recurrent EOC."

JCO Editorial: (pdf) + link to original article abstract - Tumor Genetic Testing for Patient Selection in Phase I Clinical Trials (breast, cervical, endometrial, ovarian) : The Case of PI3K Inhibitors

2012-01-28T07:06:00.000-05:00

Editorial:

"On the basis of these considerations, with mTOR and pan-PI3K
inhibitors we might need to cast a wider net and study patients with
mutations of the target gene(s) within the pathway, as well as those
without such mutations, until a stronger predictive relationship
emerges. Regardless, the availability of tumor samples should be mandatory,
and, in those cases with demonstrated clinical responses, we
should be ready to embark in deep sequencing analysis in order to
identify potential mutations indicative of sensitivity to the agents
under study."

abstract: original article:

PI3K/AKT/mTOR Inhibitors in Patients With Breast and Gynecologic Malignancies Harboring PIK3CA Mutations

Seth's Blog: The honest broker

2012-01-28T06:13:00.001-05:00

JCO Editorial: Moving Beyond Anti–Vascular Endothelial Growth Factor Therapy in Ovarian Cancer (Avastin,AMG-386)

2012-01-28T05:54:00.001-05:00

financial news: AstraZeneca cancels Olaparib trial

2012-01-28T05:41:00.000-05:00

"The drugmaker then said that its investigational compound olaparib would not progress into Phase III development for the maintenance treatment of serous ovarian cancer. Additionally, attempts to identify a suitable tablet dose for use in Phase III studies were not successful."

the Oncologist: Characteristics of Oral Mucosal Events Related to Bevacizumab (Avastin) Treatment (study of 4 patients)

2012-01-27T21:05:00.001-05:00

Background.
Bevacizumab, a monoclonal antibody targeting a vascular endothelial growth factor (VEGF) protein, has been reported to induce mucosal toxicities. However, the clinical characteristics of these particular toxicities have not been well characterized. We aimed at providing a detailed clinical description of signs and symptoms limited to the tongue mucosa in patients treated with bevacizumab.

Conclusion. These characteristic clinical findings are consistent with geographic tongue. However, large prospective evaluations are necessary to confirm this potential relationship. If bevacizumab is indeed associated with geographic tongue, increased awareness may result in improved reporting and characterization of this particular adverse event.

"Asymptomatic geographic tongue does not necessitate
treatment or bevacizumab interruption, and patients should be
reassured about the benign nature and course of this condition.
Associated symptoms may be alleviated with topical anesthetic
agents, topical or systemic antihistamines, corticosteroids,
and anxiolytics [10, 11, 14]. Successful management
with topical tretinoin, systemic acitretin, vitamin A acid therapy,
and cyclosporin has also been reported in the non-oncologic
setting [11, 14]."

conference notice: Welcome - Bienvenue | World Cancer Congress Montreal August 27-30th (UICC World Cancer Congress)

2012-01-27T21:01:00.001-05:00

UICC and its hosts Fondation québécoise du cancer, McGill University and Université de Montréal; are pleased to announce that the next UICC World Cancer Congress will take place from the 27-30 August 2012 at the Palais des Congrès Montréal, Canada.
Held every two years, the Congress represents a unique and ideal platform for the international cancer control community to meet, discuss, share, learn and connect in order to find solutions to reduce the impact of cancer on communities around the world. With this in mind the theme for the for the 2012 congress is "Connecting for Global Impact" and highlights the need for continued support and momentum in translating the benefits of knowledge gained through research and practice to those living with and affected by cancer.

open access: PLoS ONE: Immunohistochemical Profile for Unknown Primary Adenocarcinoma (CUP) (lung, digestive, gynecologic, prostate, liver, kidney, breast, urothelial, unclassified)

2012-01-27T18:58:00.001-05:00

Background

Development of tailored treatment based on immunohistochemical profiles (IPs) of tumors for cancers of unknown primary is needed.

~~~~~~~~

The primary tumor sites based on the immunohistochemical profiles (IPs) for the 71 unknown primary patients were the lung for 17 patients, digestive organs for 13, gynecological organs for 9, prostate for 7, liver/kidney for 6, breast for 4, urothelial for 2, and were not unclassified for 13 patients (Table 2).Figures 2 and 3 show typical IHC results for the breast and lung profiles.

~~~~~~~~~

Methodology/Principal Findings

"We developed an algorithm based on primary known adenocarcinoma for testing sensitivity and specificity. Formalin-fixed paraffin-embedded tissue samples from 71 patients of unfavorable subsets of unknown primary adenocarcinoma were obtained. We examined 15 molecular markers using the algorithm incorporating these IPs and classified the tumours into 9 subsets based on the primary tumour site. The sensitivity and specificity of this algorithm were 80.3% and 97.6%, respectively."

"Apparent primary sites were lung in 17 patients, digestive organs in 13, gynecological organs in 9, prostate in 7, liver or kidney in 6, breast in 4, urothelial organ in 2, biliary tract and pancreatic profile in none, and unclassified in 13."

Response evaluation (treatment plan) and survival analysis:

"...... Response rates by profile are listed in Table 2. A higher response rate was observed for the gynecological profile (67%) than for the other profiles...."

Discussion:

"...Further, we consider gynecologic profile may not be necessary to be classified into ovary, endometrial, and cervical adenocarcinoma in the situation of adenocarcinoma of unknown primary because chemotherapies for these cancer become similar in advanced disease [32], [33]..."

The algorithm we generated for orienting primary has value:

"Immunohistochemistory is generally done in routine work for the diagnosis of adenocarcinoma of unknown primary in many cancer centers. Therefore, there is no additional skill or tool in the procedure of diagnosis [10], [25]."

"This study has some limitations. First, the prognostic value of each IP was potentially underpowered, as the number of patients in each subgroup was somewhat small, not allowing the response rate, PFS, and OS to be compared to historical control data. Second, the results need to be validated in a prospective manner by applying standard treatments for identified primary profiles, to go beyond simply identifying prognostic factors for unknown primary adenocarcinoma....

"In this study, we revealed the prognostic value of a panel composed of immunohistochemistry profiles for patients with adenocarcinoma of unknown primary who received platinum doublet chemotherapy. Orienting primary sites either IHC or cDNA microarray in patients with CUPs is not good enough, we need to examine survival benefit when applying organ-oriented standard chemotherapies for patients with CUPs.
Our results may encourage a prospective randomized trial to compare standard platinum doublet chemotherapy with treatment determined by the IP. This approach may assist in developing new treatment strategy compared to a single arm platinum combination trial"

open access: Diagnostic Pathology | Abstract | Carcinoma involving the gallbladder: A retrospective review of 23 cases - pitfalls in diagnosis of gallbladder carcinoma

2012-01-27T16:55:00.002-05:00

Viewing options

Abstract
Provisional PDF (1.1MB)

Background

Carcinoma of the gallbladder (GBC) clinically mimics benign gallbladder diseases and often escapes detection until advanced stage. Despite the frequency of cholecystectomy, diagnosis of GBC remains problematic in many situations. We sought to identify pathologic features that contribute to the difficulty in recognition of GBC.

Methods

We identified 23 patients (ranged from 45 to 86 years, male to female ratio 1:4.5) with carcinoma involving the gallbladder referred to an academic medical center over a period of 10 years for study. This includes 10 cases of primary GBC, 6 cases of metastatic tumor to gallbladder, 6 cases of directly invasive adenocarcinoma arising elsewhere in the biliary tree, and one case of unidentified origin adenocarcinoma. Primary tumors include adenocarcinoma not otherwise specified (NOS) in 6 cases, papillary adenocarcinoma in 2 cases, and single cases of undifferentiated carcinoma and combined adenocarcinoma and neuroendocrine carcinoma (NEC). Metastatic tumors to gallbladder were from a wide range of primary sites, predominantly the gastrointestinal tract.

(included) Table 2 - Summary of case details in problematic cases:

ref. 10. Jain V, Gupta K, Kudva R, Rodrigues GS: A case of ovarian metastasis of gallbladder carcinoma simulating primary ovarian neoplasm: diagnostic pitfalls and review of literature. Int J Gynecol Cancer 2006, 16(Suppl 1):319-321

Weighed, Measured, and Still Searching: Bevacizumab in the Treatment of Unselected Patients with Advanced Breast Cancer - the Oncologist

2012-01-27T16:43:00.001-05:00

abstract: Spectrum of (FDG-PET/CT) fluorodeoxyglucose-positron emission tomography/computed tomography and magnetic resonance imaging findings of ovarian tumors.

2012-01-27T14:09:00.001-05:00

Abstract

The purpose of this article is to review fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) and magnetic resonance imaging (MRI) findings in a variety of benign, malignant, and borderline malignant ovarian tumors. It is advantageous to become familiar with the wide variety of FDG-PET/CT findings of this entity. Benign ovarian tumors generally have faint uptake, whereas endometriomas, fibromas, and teratomas show mild to moderate uptake. Malignant ovarian tumors generally have intense uptake, whereas tumors with a small solid component often show minimal uptake.

abstract: DICER1 in ovarian cancers : Nature Genetics (sertoli-leydig/juvenile granulosa/sex-cord stromal tumors) : Nature Publishing Group

2012-01-27T13:54:00.001-05:00

Abstract:

"Germline mutations in DICER1 underlie a rare syndrome associated with susceptibility to pleuropulmonary blastoma, cystic nephroma and ovarian sex-cord stromal tumors. David Huntsman, Gregg Morin and colleagues (N. Engl. J. Med., published online 21 December 2011; doi:10.1056/NEJMoa1102903) now show that somatic mutations in DICER1 occur at high frequency in non–epithelial ovarian cancers. The authors performed transcriptome and exome sequencing in two Sertoli-Leydig cell tumors, four juvenile granulosa cell tumors and eight primitive germ cell tumors and identified four missense mutations in DICER1 affecting the metal-binding region of the RNase IIIb domain. They subsequently sequenced the portion of DICER1 encoding this region in 101 additional non-epithelial ovarian tumors and identified somatic mutations in 60% of Sertoli-Leydig cell tumors........ On the basis of these findings, the authors propose that these mutations result in an oncogenic miRNA profile whose pathogenicity may be restricted to specific cell types or developmental settings, thereby accounting for the high prevalence of these mutations in particular tumor types."

abstract: Long-Term Clinical Outcome of Patients With Recurrent Epithelial Ovarian Carcinoma: Is it the Same for Each Histological Type?

2012-01-27T13:48:00.001-05:00

Abstract

Objectives: This study was conducted to estimate the long-term clinical outcome of patients with recurrent ovarian carcinoma (ROC).

Conclusions: Despite the continuous administration of treatment for ROC, survival is poor, and the extent of therapeutic progress differs according to the histological type.

intereview with Dr David M. Gershenson: Clinical Challenges of Low-Grade (serous) Ovarian Cancer (includes comment on BRAF mutations, borderline tumors, age...)

2012-01-27T13:35:00.001-05:00

Editor's Note:

About 10% of all serous ovarian carcinomas are low grade. Recent research indicates that these tumors differ in major ways from high-grade serous ovarian carcinomas. David M. Gershenson, MD, who holds the J. Taylor Wharton, MD, Distinguished Chair in Gynecologic Oncology at The University of Texas MD Anderson Cancer Center in Houston, Texas, discussed with Medscape current approaches to low-grade serous carcinoma of the ovary and peritoneum.
...............................................................

Blogger's Note: a selected item below - read full article for more information:

Medscape: What is the next step for LGSC clinical research?
Dr. Gershenson: The major finding in the GOG 0239 study was a higher response with the MEK inhibitor than with conventional chemotherapy or hormonal therapy, so these drugs need to be studied further. They should also be tested in conjunction with drugs that block the PI3-kinase/Akt pathway. Dual pathway blockade may be required to produce a more robust response.
In the GOG 0239 trial, we saw a response rate of slightly over 15%, which is about 3-fold higher than with conventional chemotherapy and about 50% higher than with hormonal therapies in the recurrent setting. Unlike the situation with melanoma, there was no correlation with mutational status. That was something of a surprise and suggests that we don't understand what the impact of having a mutation is. I was certainly disappointed that there was not a correlation. We are looking at other markers in that pathway using data from that trial, and that analysis has not yet been completed..........

....Finally, the principal advance over the past decade is the recognition of LGSC as a distinct entity^[9] -- very different from the typical high-grade ovarian cancers. Women with this subtype deserve separate clinical trials and treatment options.

Cochrane Review: abstract - Robotic assisted surgery for gynaecological cancer.

2012-01-27T13:31:00.001-05:00

Abstract

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.

OBJECTIVES:

To evaluate the evidence for and against robotic assisted surgery in gynaecological cancer.
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.

AUTHORS' CONCLUSIONS:

Well-designed RCTs are required as only low quality evidence from CCTs is available. These studies support the use of robotic assisted surgery for endometrial cancer and cervical cancer, but these findings present a high risk of bias.

Common Gastro Disease Occurs Even With High-Fiber Diet - Drugs.com MedNews

2012-01-27T13:24:00.001-05:00

FRIDAY Jan. 27, 2012 -- Eating a high-fiber diet does not lower a person's risk of diverticulosis, but a low-fiber diet might, according to a new study that contradicts what doctors have believed for decades....

abstract: Phase I clinical trial of alternating belotecan and oral etoposide in patients with platinum-resistant or heavily treated ovarian cancer (total 6 patients/phase 1)

2012-01-27T11:50:00.001-05:00

Abstract:
This study was designed to determine the maximum tolerated dose and toxicity profile of belotecan in combination with oral etoposide in patients with platinum-resistant or heavily treated ovarian cancer, fallopian tubal cancer, and primary peritoneal cancer.

"....Thus, the maximum tolerated dose was reached (50 mg of oral etoposide) and the trial was terminated. The response was evaluable in nine patients and an objective response was observed in four patients (44%) including two complete responses."

medical press: study - Researchers analyze doctor-patient email interactions

2012-01-27T11:42:00.004-05:00

“.......There were some very interesting findings in how practitioners use email versus how patients use it,” Geana said....."

"Treatments and lab tests were the most common topics of discussion for both patients and providers."

"Patient to physician email communication is slowly growing as a means of communication within health care. But it is still underutilized and not well-integrated into electronic health records systems,” Greiner said. “Many physicians are still resisting email interactions with patients out of fear of being overwhelmed by a large number of patients. This concern will only be ameliorated when the health care system moves from bricks and mortar, hospital-centered care, to more patient-centered approaches. Understanding the content of doctor-patient emails now, should help us build systems that take advantage of all new communication technologies."

abstract: Implementing an online tool for genome-wide validation of survival-associated biomarkers in ovarian-cancer using microarray data from 1287 patients.

2012-01-27T11:32:00.001-05:00

Abstract

"The validation of prognostic biomarkers in large independent patient cohorts is a major bottleneck in ovarian cancer research. We implemented an online tool to assess the prognostic value of the expression levels of all microarray quantified genes in ovarian cancer patients. First, a database was set up using gene expression data and survival information of 1,287 ovarian cancer patients downloaded from GEO and TCGA (Affymetrix HGU133A, HGU133A 2.0 and HGU133+2 microarrays).

After quality control and normalization only probes present on all three Affymetrix platforms were retained (n=22,277). To analyze the prognostic value of the selected gene, the patients are divided into two groups according to various quantile expressions of the gene. These groups are then compared using progression free survival (n=1,090) or overall survival (n=1,287). A Kaplan-Meier survival plot is generated and significance is computed. The tool can be accessed online at www.kmplot.com/ovar. We used this integrative data analysis tool to validate the prognostic power of 37 biomarkers identified in the literature.

Of these, CA125 (p=3.7e-5, HR=1.4), CDKN1B (p=5.4e-5, HR=1.4), KLK6 (p=0.002,HR=0.79), IFNG (p=0.004, HR=0.81), P16 (p=0.02, HR=0.66) and BIRC5 (p=0.00017, HR=0.75) were associated with survival. The combination of several probe sets can further increase prediction efficiency.

In summary, we developed a global online biomarker validation platform that mines all available microarray data to assess the prognostic power of 22,277 genes in 1,287 ovarian cancer patients.

We specifically used this tool to evaluate the effect of 37 previously published biomarkers on ovarian cancer prognosis."

not yet recruiting: Trial of (neoadjuvant) Chemotherapy in Ovarian, Fallopian Tube and Peritoneal Carcinoma - Full Text View - ClinicalTrials.gov

2012-01-27T10:49:00.001-05:00

Trial of Chemotherapy in Ovarian, Fallopian Tube and Peritoneal Carcinoma

This study is not yet open for participant recruitment.

Verified January 2012 by University of Kentucky

First Received on January 18, 2012. Last Updated on January 26, 2012 History of Changes

Purpose

This is a prospective study to evaluate the hypothesis that platinum-based neoadjuvant chemotherapy followed by interval surgical debulking with platinum-based adjuvant chemotherapy is associated with improved maximal surgical cytoreduction rates, comparable survival, decreased morbidity, and increased quality of life in patients with International Federation of Gynecologic Oncology stages IIIC and IV ovarian, primary peritoneal, or fallopian tube cancer when compared to historical controls and to evaluate the hypothesis that cancer induced inflammation is a predictor of poor prognosis and response to therapy in this group of ovarian cancer patients.

CCR Clinical Trials at NIH: Clinical Research: Search for Clinical Trials at NIH

2012-01-27T07:59:00.001-05:00

There are 31 clinical trials at NIH that match your search criteria
- Cancer by type/disease: Solid Tumor (Adult)

CCR Clinical Trials at NIH: Clinical Research: Search for Clinical Trials at NIH

2012-01-27T07:57:00.001-05:00

There are 14 clinical trials at NIH that match your search criteria:
Cancer by type/disease: Ovarian Cancer

open access: Evaluation of Genomic Applications in Practice and Prevention (EGAPP) (breast, ovarian, Lynch Syndrome...)

2012-01-27T07:38:00.001-05:00

Evaluation of Genomic Applications in Practice and Prevention (EGAPP): Implementation and Evaluation of a Model Approach

The EGAPP initiative was launched by the CDC Office of Public Health Genomics in the fall of 2004. The initiative's goal is to establish and evaluate a systematic, evidence-based process for assessing genetic tests and other applications of genomic technology in transition from research to clinical and public health practice. EGAPP also aims to integrate:

existing recommendations on implementation of genetic tests from professional organizations and advisory committees.^1,2,3,4
knowledge and experience gained from existing processes for evaluation and appraisal (e.g., US Preventive Services Task Force, CDC’s Task Force on Community Preventive Services), previous CDC initiatives (e.g., the ACCE process for assembling and analyzing data on genetic tests; http://www.cdc.gov/genomics/gtesting/ACCE/FBR/index.htm) 5, and the international health technology assessment experience.

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

Working Group: Topics

Completed Topics | Topics Under Review | Topics Identified

conference: EGAPP Working Group Jan 30-31 Atlanta, GA

2012-01-27T07:29:00.000-05:00

The 23^rdMeeting of the EGAPP Working Group will be held in Atlanta on January 30-31st, 2012.

New Grief blog| Barbara Okun, PhD. and Joseph Nowinski, PhD. Blog

2012-01-27T07:25:00.001-05:00

"Welcome to a conversation focused on helping you and your family deal with new grief."

Joseph Nowinski, Ph.D.: When Does Grief Become Mental Illness? (also: the 'new' grief)

2012-01-27T07:22:00.000-05:00

open access: MRI, CT, and PET/CT for Ovarian Cancer Detection and Adnexal Lesion Characterization February 2010

2012-01-26T23:13:00.001-05:00

OBJECTIVE. The purpose of this article is to describe the role of MR, CT, and PET/CT in the detection of ovarian cancer and the evaluation of adnexal lesions.

open access: NCI’s provocative questions on cancer: some answers to ignite discussion - Oncotarget

2012-01-26T22:55:00.001-05:00

National Cancer Institute has announced 24 provocative questions on cancer.......

view article for more information - eg. PQ-19: Why are some disseminated cancers cured by chemotherapy alone?; PQ-5: Given the evidence that some drugs commonly and chronically used for other indications, such as an anti-inflammatory drug, can protect against cancer incidence and mortality, can we determine the mechanism by which any of these drugs work? (aspirin...); PQ-1: How does obesity contribute to cancer risk?.......

Outcomes Research Institute Releases Priorities - in Public Health & Policy, General Professional Issues from MedPage Today - comments until March 15

2012-01-26T22:30:00.001-05:00

WASHINGTON -- The new institute created by the Affordable Care Act (ACA) to study which medical treatments are the most effective will focus on broad areas of healthcare instead of specific drugs or procedures, according to a draft of its research priorities.
The institute, called the Patient Centered Outcomes Research Institute (PCORI), is a nonprofit organization with a 21-member board that will identify areas that can benefit from comparative effectiveness research, fund the research through $3 billion in grants over the next decade, and provide patients and clinicians with research findings.
Opponents of the healthcare reform law charge that PCORI will make decisions that will lead to clinical rationing.
Supporters of the ACA, however, say comparative effectiveness research is crucial to improving the U.S. healthcare system and that it won't lead to denying access to certain drugs or procedures. The law specifically prohibits the panel's recommendations from being "construed as mandates for practice guidelines, coverage recommendations, payment, or policy recommendations."........
.....................................................................................................................
In draft recommendations released Monday, the PCORI board identified five broad areas where it determined comparative effectiveness research is needed. They are:

Assessment of options for prevention, diagnosis, and treatment, with research focusing on patient preferences and decision-making as well as various factors that may affect patient outcomes.
Improving healthcare systems, including focusing on coordination of care for patients with multiple medical conditions, and how use of nonphysician providers affects patient outcomes.
Communication and dissemination of research, including ways to provide information to patients that helps them to talk with their healthcare providers about it, and ways to use electronic data (e-records) to support decision-making.
Addressing disparities, including ensuring that research into the benefits and risks of various medical options addresses the needs of all patient populations.
Designing "quick, safe, and efficient" patient-centered outcomes research and methodological research, and studying ways to improve the quality and usefulness of clinical data and follow-up studies.

"These priorities and agenda give a framework to and identify the broad questions that must be addressed so that patients can make better and more personalized decisions in partnership with their clinicians across all areas of health," said PCORI Executive Director Joe Selby, MD, MPH, in a press release.
Selby added that the early agenda is a starting point and PCORI hopes that patients, healthcare providers, and others will provide feedback and "think boldly" about research projects in all five areas.
The draft will be available for public comment until March 15, and PCORI will hold a public meeting in Washington on Feb. 27.

abstract: Correlation between body mass index and prevalence of hereditary nonpolyposis colorectal cancer (Lynch Syndrome) in korean patients (endometrial cancer)

2012-01-26T21:53:00.001-05:00

CONCLUSION:
However, BMI proportions in the patients with HNPCC related to endometrial cancer was significantly different from those in sporadic endometrial cancer. Specifically, among nonobese patients, the proportion of normal weight was significantly high in Korean women with HNPCC.

abstract: Lymph node metastasis in stages I and II ovarian cancer: a review.

2012-01-26T21:40:00.001-05:00

CONCLUSIONS:

The incidence of lymph node metastases in clinical early stage EOC is considerable. Based on the scarce literature data, omitting a systematic lymphadenectomy can only be considered in grade I mucinous tumors.

Medpage article - Mark Britton (author) : The Internet is where patients go for pre-visit consultations

2012-01-26T20:39:00.001-05:00

Mark Britton is the founder and CEO of Avvo, a free resource that rates and profiles 90% of all doctors and lawyers in the U.S.

"...For those skeptics, let me offer the following:

80% of Internet users search for health information online
44% research doctors online
43% ask questions in online forums
45% ask questions to be better prepared for a physician visit
13 minutes: Average duration of a physician visit.........."

(UK) Minister denies (ovarian) cancer test pressure - GP online

2012-01-26T20:30:00.001-05:00

Blogger's Note: assumption: the ovarian 'cancer test' refers to the CA-125

OTC Supplement Dims Ovarian Cancer | www.dailyrx.com

2012-01-26T20:23:00.000-05:00

Anticoagulant loses its lustre : The Lancet (dabigatran/patient safety)

2012-01-26T20:18:00.001-05:00

Jan 2012 BRCA patent dispute may head to US Supreme Court : The Lancet

2012-01-26T20:12:00.002-05:00

"The long-running dispute over patents for the BRCA1 and BRCA2 genes granted to Myriad Genetics may finally be laid to rest by the US Supreme Court....."

Medical News: FDA Supplement Guidance Not Strict Enough, MD Says - in Public Health & Policy

2012-01-26T20:04:00.000-05:00

Medical News: FDA Targets Drugs Sold as Supplements - in Public Health & Policy

2012-01-26T20:03:00.001-05:00

New (subspecialty) Certification for Complex Surgical Oncology - OncologySTAT

2012-01-26T16:28:00.001-05:00

"A new subspecialty certification in complex general surgical oncology aims to provide surgeons with training in the diagnosis, treatment, and rehabilitation of patients with complex cancers such as sarcoma, melanoma, and esophageal malignancies - and hopefully will attract surgeons who want to focus on research...."

New Anticoagulants for Venous Thromboembolism - Oncology and Hematology

2012-01-26T16:21:00.000-05:00

Published in Journal Watch Oncology and Hematology February 8, 2011

Citation(s):

Lassen MR et al. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med 2010 Dec 23; 363:2487.

Medline abstract (Free)

Bauersachs R et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010 Dec 23; 363:2499.

Medline abstract (Free)

open access: Risk of venous and arterial thromboembolic events associated with anti-EGFR agents: a meta-analysis of randomized clinical trials

2012-01-26T16:16:00.001-05:00

summary: Risk of Venous and Arterial Thromboembolic Events Associated With Anti-EGFR Agents: A Meta-Analysis of Randomized Clinical Trials - OncologySTAT

2012-01-26T16:09:00.002-05:00

SUMMARY

OncologySTAT Editorial Team

"Venous and arterial thromboembolism events (VTEs and ATEs) are common in patients with cancer and are a frequent cause of mortality in these patients. Antiangiogenic agents that target vascular endothelial growth factor receptor (VEGFR), such as sunitinib, sorafenib, and bevacizumab, are associated with increased risk of VTEs and ATEs. Other drugs target the epidermal growth factor receptor (EGFR), such as the monoclonal antibodies cetuximab and panitumumab, and the oral tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib. This meta-analysis evaluated the risk of VTEs and ATEs associated with the anti-EGFR agents cetuximab, panitumumab, erlotinib, and gefitinib.
Medline and EMBASE were searched for randomized controlled phase II or III trials in which cetuximab, panitumumab, erlotinib, or gefitinib was used as treatment for patients with cancer....."

US Oncologists Confront Pressure to Curb Cancer Costs - OncologySTAT

2012-01-26T16:07:00.002-05:00

abstract: Family History and Women With Ovarian Cancer: Is it Asked and Does it Matter?: An Observational Study BRCA and/or Lynch Syndrome

2012-01-26T10:09:00.001-05:00

Abstract

Objective: The objective of the study was to determine how many women in an ovarian cancer (OC) study cohort had a family history (FH) recorded in their case notes and whether appropriate action was taken on the basis of that FH.

Results: Family history was not consistently recorded. Although FH was recorded in the majority of women, 14 women had no FH recorded. In 63 women, the FH was recorded as not significant, and in 15 cases, FH information was insufficient to complete a risk assessment. Twenty-two women had significant FH meeting criteria for specialist genetics referral. In 15 of these 22 cases, the relevant history suggestive of hereditary breast cancer and OC (due to BRCA1 or BRCA2 mutations) or Lynch syndrome had been documented, but no action was recorded, and its significance was not appreciated.

Conclusions: These data indicate that training in recognizing relevant FH is needed for clinicians looking after women with OC. .....

media: (Ontario, Canada) OHIP turns blind eye to suffering | London | News | London Free Press - McMaster University/Ontario Healthcare Minister/gynecology + public comments/add your comments

2012-01-26T07:33:00.001-05:00

Blogger's Note: it is possible that all details are not included in this media item, however, as the article states, neither the gynecologist at McMaster nor the Ontario Healthcare Minister commented.
.......................................................................................................

One specialist, Dr. Alexandre Nevin Lam, chastised Jones for seeking faster access, writing in a letter she should stop "doctor shopping, since this was a waste of both health-care resources and her time."

"Board members took issue not just with the stance of OHIP, but also with the Ontario specialists who had essentially told Jones to wait her turn.
The specialist she was to have waited for was Dr. Nicholas Leyland, top dog at Health Sciences Centre at Hamilton's McMaster University. But when Jones went to Sinervo, Leyland wrote to support OHIP's denial of coverage. "It is unfortunate that Dr. Leyland did not testify at the hearing," the board wrote."

"The Free Press requested interviews three days this week with Matthews, (Ontario Health Minister) a London MPP, but she didn't make herself available."
.....................................................................

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video: HBOC Oct 2011: Cell of origin of ovarian cancer - Prof Louis Dubeau - University of Southern California, Los Angeles, USA

2012-01-26T07:17:00.001-05:00

video: CFS Nov 2011: Active angiogenesis drugs in development - Prof Bradley Monk – University of California Irvine, USA

2012-01-26T07:15:00.001-05:00

abstract: A literature review of quality in lower gastrointestinal endoscopy from the patient perspective.

2012-01-26T06:47:00.001-05:00

Abstract

BACKGROUND:

Given the limited state of health care resources, increased demand for colorectal cancer (CRC) screening raises concerns about the quality of endoscopy services. Little is known about quality in colonoscopy and endoscopy from the patient perspective.

OBJECTIVE:

To systematically review the literature on quality that is relevant to patients who require colonoscopy or endoscopy services.

METHODS:

A systematic PubMed search was performed on articles that were published between January 2000 and February 2011.

"Qualitative studies eliciting the patient perspective on what constituted quality in colonoscopy⁄endoscopy were not found."

press release: Elsevier's Maturitas (European Menopause and Andropause Society (EMAS) ) publishes position statement on the role of vitamin D in postmenopausal women

2012-01-26T06:33:00.001-05:00

Seth's Blog: Who cares?

2012-01-26T05:45:00.001-05:00

"....Which is precisely what makes it valuable."

BioMed Central Blog : DIM: hope for ovarian cancer (anti-cancer drug Diindolylmethane (DIM))

2012-01-26T05:37:00.001-05:00

"Importantly, Kandala and Srivastava also showed that DIM enhanced the anti-cancer effects of cisplatin in both human ovarian cancer cells and in mice, where a combination of both drugs reduced tumour growth by an extra 50% compared with cisplatin alone. DIM is thus an exciting potential future therapy for ovarian cancer, which could overcome the problems with cisplatin resistance in some women."

Search of: vaccine ovarian | Open Studies - List Results - ClinicalTrials.gov 25 open studies)

2012-01-25T22:11:00.001-05:00

Found 25 studies with search of: vaccine ovarian | Open Studies

Vaccine Therapy and OPT-821 or OPT-821 Alone in Treating Patients With Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer in Complete Remission - Full Text View - ClinicalTrials.gov

2012-01-25T22:09:00.001-05:00

Vaccine Therapy and OPT-821 or OPT-821 Alone in Treating Patients With Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer in Complete Remission

The recruitment status of this study is unknown because the information has not been verified recently.

Verified July 2008 by National Cancer Institute (NCI). Recruitment status was Not yet recruiting

First Received on June 6, 2008. Last Updated on July 27, 2011 History of Changes

Sponsor:	Gynecologic Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00693342

(NEJM)The New England Journal of Medicine: 3 artiicles - breast cancer/Avastin (Bevacizumab) Jan 2012

2012-01-25T21:59:00.001-05:00

original article (abstract)

Bevacizumab and HER2-Negative Breast Cancer

original article (abstract)

Bevacizumab in Neoadjuvant Breast-Cancer Therapy

editorial (excerpt)

Fighting Fire with Fire: Rekindling the Bevacizumab Debate

open access: Perspective: Assessing Supplement Safety — The FDA's Controversial Proposal — NEJM

2012-01-25T21:49:00.002-05:00

"Each year, Americans spend more than $28 billion on supplements assuming that they are both safe and effective. More than 100 million Americans consume vitamins, minerals, herbal ingredients, amino acids, and other naturally occurring products in the form of dietary supplements....."

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

2012-01-25T17:45:00.001-05:00

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

2012-01-25T16:18:00.001-05:00

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

2012-01-25T12:16:00.001-05:00

"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?

2012-01-25T12:07:00.001-05:00

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

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

2012-01-25T06:41:00.001-05:00

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

2012-01-25T06:30:00.001-05:00

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)

2012-01-25T06:19:00.001-05:00

"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)

2012-01-25T05:27:00.001-05:00

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.

(repost) abstract: Re-operation outcome in patients referred to a gynecologic oncology center with presumed ovarian cancer FIGO I-IIIA after sub-standard initial surgery (eg. ethics, survival issues)

2012-01-25T05:14:00.001-05:00

Blogger's Note: after decades, this issue remains; search blog posts for related data; questions remain regarding patients safety (eg. survival); ethics

Conclusion

Comprehensive staging of presumed early ovarian cancer has been described as major problem especially outside gynecologic oncology units. Re-staging results in our department confirmed this deficiency by showing a considerable proportion of upstaging associated with alterations of recommendations for systemic treatment.

However, series like this may even underestimate the problem, because incomplete staging is unfortunately accompanied by non-systematic referral practices not reflecting staging quality.

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

2012-01-25T04:50:00.001-05:00

"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

2012-01-25T04:26:00.000-05:00

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

2012-01-24T21:26:00.001-05:00

"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

2012-01-24T21:23:00.001-05:00

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

2012-01-24T20:51:00.001-05:00

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

2012-01-24T20:24:00.001-05:00

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)

2012-01-24T20:17:00.001-05:00

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

2012-01-24T19:53:00.002-05:00

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

2012-01-24T17:56:00.001-05:00

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.....

2012-01-24T17:37:00.001-05:00

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

2012-01-24T17:18:00.004-05:00

"....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

2012-01-24T12:39:00.001-05:00

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

2012-01-24T12:25:00.001-05:00

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])

2012-01-24T12:03:00.003-05:00

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

2012-01-24T09:39:00.001-05:00

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

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

2012-01-24T09:30:00.001-05:00

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

2012-01-24T09:27:00.001-05:00

"....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?

2012-01-24T03:46:00.001-05:00

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

2012-01-24T02:57:00.001-05:00

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

2012-01-24T02:29:00.003-05:00

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

2012-01-24T02:06:00.001-05:00

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)

2012-01-24T01:58:00.001-05:00

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

2012-01-23T21:07:00.001-05:00

“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

2012-01-23T20:29:00.001-05:00

"...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

2012-01-23T20:25:00.001-05:00

"....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

2012-01-23T11:06:00.003-05:00

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

2012-01-23T11:04:00.001-05:00

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

2012-01-23T07:43:00.001-05:00

"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

2012-01-23T07:42:00.001-05:00