Is it equivalent? Evaluation of the clinical activity of single agent Lipodox® compared to single agent Doxil® in ovarian cancer treatment.

abstract

BACKGROUND:

In response to the critical shortage of liposomal doxorubicin (Doxil®) in the United States, the Food and Drug Administration (FDA) approved temporary importation of doxorubicin hydrochloride liposome (Lipodox®). The objective was to compare toxicity and clinical activity of Lipodox® with Doxil®.

METHODS:

Recurrent ovarian cancer patients who received Lipodox® were compared 3:1 to matched control Doxil® patients who had received Doxil®. Patients were matched based on age, stage, dose, platinum sensitivity, and prior treatments from an existing de-identified database. Patients receiving combination regimens were excluded.

RESULTS:

The data from 40 Lipodox® patients was compared to 120 matched control Doxil® patients. In this study, 17 (42.5%) of the Lipodox® patients were switched to Doxil®. The overall response rate Lipodox® was 4.3% (1/23) compared to 18% (20/111) in matched control Doxil® patients. In the platinum-sensitive patients, 100% progressed in the Lipodox® group compared to 78.4% in matched control Doxil® patients. The mean time to progression was 4.1 ± 2.8 months for Lipodox® and 6.2 ± 7.2 months in control Doxil®s (p = 0·25). Toxicity was similar in the Lipodox® group and control Doxil® group.

CONCLUSION:

Lipodox® for treatment of recurrent ovarian cancer did not appear to have equivalent efficacy compared to Doxil®. A prospective clinical study is warranted before Lipodox® can be deemed equivalent substitution for Doxil®.

Comparison of Clinical Characteristic and Prognosis between Ovarian Clear Cell Carcinoma and Serous Carcinoma

open access

Comparison of Clinical Characteristic and Prognosis between Ovarian Clear Cell Carcinoma and Serous Carcinoma: A 10-Year Cohort Study of Chinese Patients

 Objectives

To compare the clinicopathologic features and prognosis of Chinese patients with ovarian clear cell carcinoma (CCC) and serous carcinoma (SC).

Methods

A retrospective cohort study was designed to investigate the clinicopathologic characteristic and prognosis of patients with CCC and SC who were diagnosed and treated in in a tertiary referral center (Peking Union Medical College Hospital) between 1999 and 2009. The Kaplan-Meier method and Cox regression were employed in the survival analysis.

Results

A total of 504 cases were included in the study, comprising 197 cases of CCC and 307 cases of SC. The mean age of the patients with SC was greater than of CCC patients (3.6±0.94, P<0.001). Patients with CCC were more likely to be early-stage and optimally debulked (P<0.001). Regarding cancer-antigen 125, 22% of the patients with CCC had normal values, and the level was significantly lower than in patients with SC (P<0.001). More CCC patients had platinum-resistant tumors compared with platinum-sensitive disease (45.7% in CCC vs. 61.0% in SC [P=0.008]). The 5-year survival rate was 51.2% in the CCC group vs. 49.8% in the SC group (P=0.428). Patients with advanced CCC had a statistically significant poorer overall survival (OS) compared with their SC counterparts (38.0 vs. 52.0 months; hazard ratio 1.584, 95% confidence interval [CI] 1.167-2.150, P=0.003). However, the advantage of improved progression-free survival (PFS) existed across all stages.

Conclusions

Women with ovarian CCC presented at a younger age and early stage. Patients with ovarian CCC also had improved PFS, but they had similar OS compared to patients with SC. However, patients with advanced CCC had decreased survival.

Spectrum and frequencies of BRCA1/2 mutations in Bulgarian high risk breast cancer (ovarian) patients

open access

Conclusions

This is the first comprehensive study of the BRCA1/2 mutation spectrum in Bulgaria and will assist the establishment of efficient protocols for genetic testing and individualized risk assessment for Bulgarian breast/ovarian cancer patients and healthy individuals at a high-risk.

Family with MSH2 mutation presenting with keratoacanthoma and precancerous skin lesions

abstract - case report

Muir–Torre syndrome (MTS) is a familial cancer syndrome characterized by a predisposition to keratoacanthoma (KA) and sebaceous tumors. Although MTS and hereditary non-polyposis colorectal cancer (HNPCC) share the same genetic alterations in mismatch repair (MMR) genes, the other skin lesions in MTS or HNPCC have been only rarely reported. We report a family with an MSH2 mutation c.1126_1127delTT (p.Leu376Thrfs*12). A 46-year-old male proband developed KA with sebaceous differentiation, colon cancer and gastric cancer, and fulfilled the diagnostic criteria for MTS. His 80-year-old mother, diagnosed with HNPCC, presented with multiple gastrointestinal tract cancers, Bowen's disease and actinic keratosis. Immunostaining revealed attenuated MSH2 protein expression in KA, as well as in Bowen's disease and actinic keratosis lesions. These findings suggest that MMR gene abnormality is also critical in the development of benign or malignant cutaneous tumors such as actinic keratosis and Bowen's disease in MTS/HNPCC patients.

MRI Imaging Characteristics of Ovarian Clear Cell Carcinoma

Blogger's Note: Table 1 shows signs/symptoms; followup <30 mo; wide variance in CA125's; 8/19 pts = ascites (malignant/non-malignant)

"...CA 125 serum level (normal, < 35 U/mL) was elevated in 17 patients..."

Table 1. Clinical findings of 19 patients with OCCCs

Table 2. MRI characteristics of 21 OCCCs in 19 patients.

open access

"Despite diagnosis at early stages, OCCCs are biologically aggressive neoplasms. The presenting symptoms include abdominal discomfort, pain, distention and gastrointestinal symptoms."

Purpose

To probe the magnetic resonance imaging (MRI) features of ovarian clear cell carcinoma (OCCC).

Methods

This study retrospectively collected MRI data for 21 pathology-confirmed OCCCs from 19 female patients. The MRI findings were analyzed to determine the tumor size, shape/edge, shape and number of protrusions within the cyst, cystic or necrotic components, signal intensity (SI) and enhancement features.

Results

The age of the 19 patients ranged from 28 to 63 years (mean age: 53 years). Unilateral tumors were found in 17 patients (17/19, 89%); the average size of all tumors was 10.8 cm.....

Fair Shares/Sharing Fairly: A Survey of Public Views on Open Science, Informed Consent and Participatory Research in Biobanking

open access

"These findings suggest that current consent models such as traditional or broad consent alone do not completely address participants’ expectations."

Understanding next generation sequencing in oncology: A guide for oncologists

open access

BRCA1 and BRCA2 genetic testing – pitfalls and recommendations for managing variants of uncertain clinical significance

open access

 Members of the Clinical Working Group of  ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) global consortium (www.enigmaconsortium.org) observed wide variation in practices in reporting, disclosure and clinical management of patients with a VUS (variants of unknown significance). Examples from current clinical practice are presented and discussed to illustrate potential pitfalls, explore factors contributing to misinterpretation, and propose approaches to improving clarity


 Results and conclusion
Clinicians, patients and their relatives would all benefit from an improved level of
genetic literacy.Genetic laboratories working with clinical geneticists need to agree on a clinically clear and uniform format for reporting BRCAtest results to non-geneticists.  An international consortium of experts, collecting and integrating all available lines of evidence and classifying variants according to an internationally recognized system will facilitate reclassification of variants for clinical use.

Editorial: The Yin and Yang of Germline TP53 Mutations in Li-Fraumeni Syndrome

open access

"Remarkably, 18 mutation carriers (4%) developed a cancer during the first year of life."

 Li Fraumeni syndrome (LFS) is one of the most well-recognized cancer predisposition syndromes and serves as a paradigm for the study of heritable susceptibility to cancer. LFS was first reported in 1969 by Li and Fraumeni on the basis of the identification of four families characterized by the autosomal dominant transmission of early-onset tumors.^1,2.....

 Reference to: Revisiting Li-Fraumeni Syndrome From TP53 Mutation Carriers

JCO Jul 20, 2015:2345-2352; published online on May 26, 2015; 10.1200/JCO.2014.59.5728.

• [Abstract]
• [Full Text]
• [PDF]

natural variation in gene expression - selected articles 2015

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Natural Variation in Gene Expression Modulates the Severity of Mutant Phenotypes: Cell

abstract

Highlights

• •Comparison of loss-of-function phenotypes of 1,400 genes in two C. elegans isolates
• •∼20% of genes have different loss-of-function phenotypes in two individuals
• •Differences in severity of mutant phenotypes predictable from expression

Summary

Many mutations cause genetic disorders. However, two people inheriting the same mutation often have different severity of symptoms, and this is partly genetic. The effects of genetic background on mutant phenotypes are poorly understood, but predicting them is critical for personalized medicine. To study this phenomenon comprehensively and systematically, we used RNAi to compare loss-of-function phenotypes for ∼1,400 genes in two isolates of C. elegans and find that ∼20% of genes differ in the severity of phenotypes in these two genetic backgrounds. Crucially, this effect of genetic background on the severity of both RNAi and mutant phenotypes can be predicted from variation in the expression levels of the affected gene. This is also true in mammalian cells, suggesting it is a general property of genetic networks. We suggest that differences in the manifestation of mutant phenotypes between individuals are largely the result of natural variation in gene expression.

 

Hospitalization Rates Among Survivors of Young Adult Malignancies

abstract

 Conclusion Survivors of young adult cancers have an increased rate of hospitalization compared with controls. The rate of hospitalization for 20-year survivors did not return to baseline, indicating a substantial and persistent burden of late effects among this generally young population.

ASCO Statement: A Conceptual Framework to Assess the Value of Cancer Treatment Options

open access
 
The work of the ASCO Value in Cancer Care Task Force has been guided by the following core principles:

• The physician-patient relationship is of central importance in defining management options for the patient. It is the view of ASCO that the oncologist is the patient's best advocate and resource for guidance in assessing the value of treatment options. To accomplish this, the oncologist must have the knowledge and tools necessary to assess the relative value of therapies for specific clinical scenarios and use these in discussing treatment options with the patient.
• To ensure informed decision making, patients need access to both clinical and cost information about their treatment options. Patients need a clear understanding of the possible clinical benefits and harms of treatment options available to them, along with an appreciation of how these options differ with respect to the relative financial consequences they will face...........
  
  Table 1:  Summary of International Value Determination Frameworks
  
   Fig 1. ASCO Value Framework: advanced disease
  

  Future versions of the framework will allow for patients weighting their preferences such that the fractional contribution of each element (clinical benefit, toxicity) to the overall score can be modified, thereby individualizing the net health benefit. ASCO, American Society of Clinical Oncology; CR, complete response; DAC, drug acquisition cost; OS, overall survival; PFS, progression-free survival; PR, partial response; RR, response rate. 

  
  

  
  

  CALL FOR COMMUNITY COMMENT

  We appreciate that developing a method for establishing value of specific cancer treatment regimens is a daunting task. ASCO views this as an iterative process and encourages comments from all interested parties regarding the elements we have included in the value framework and its utility in facilitating discussion between providers and patients on the value of available treatment options. Comments may be submitted through August 21, 2015, at www.asco.org/value.

  On the basis of these comments, ASCO envisions publishing additional iterations of the framework, practical applications, recommendations regarding the additional evidence needed to develop the most useful value tools, and more detailed examinations of value in these and other disease states.

Recommendations for the Use of WBC Growth Factors: ASCO Clinical Practice Guideline Update

open access

Fraser Institute findings and methodology on wait times criticized by CDM

Newsroom
 

July 14, 2015

The Medical Post

A new study released by the Fraser Institute suggests that wait times in 2014 cost Canadians $1.2 billion in lost income and productivity, but the methods used by the research group to arrive at those figures has come under fire.

According to the study, the 937,345 patients—who spent an average of 9.8 weeks waiting for medical treatment—lost an average of $1,289 each.

The figure was calculated using a methodology developed by Fraser analysts Steven Globerman and Lorna Hoye in the early 90s.

The researchers multiplied the total number of weeks a patient spends waiting for care (provided by specialists during their annual survey) by the proportion of that time that’s rendered unproductive by the physical and emotional impact of their untreated medical condition.

The authors then factor in the average weekly wages of Canadians in each province to determine the total lost income.

“Whether it’s actually lost income from not working, lower productivity, or reduced engagement with friends and family, waiting is costing Canadians dearly,” said Bacchus Barua, a senior economist at the Fraser Institute and co-author of the study.

However, Dr. Ryan Meili, a family physician in Saskatchewan and Vice Chair of Canadian Doctors for Medicare, voiced some particularly severe criticisms of the study. He said it is “worse than noise—it’s noise with an agenda.”

“Their purpose is to say ‘the sky is falling, we must privatize.’One, their conclusion is wrong, they don’t know whether the sky is falling or not. (He took aim at their methodology to determine wait times, pointing to previous work by health policy consultant Steven Lewis). Two, their solution to that diagnosis is wrong. If we increase more private care we won’t shorten wait times, we’ll actually lengthen them.”.....

Expert Commentary on Frequently Asked Questions in Ovarian Cancer

open access

Bradley Monk, MD, FACS, FACO 

Expert Commentary on Frequently Asked

Questions in Ovarian Cancer:

Unraveling the Risks and Benefits of Antiangiogenic

 Therapy for Ovarian Cancer Patients

  AXIS Medical Education

  A CME-certified grand rounds and webinar series  entitled, Unraveling the Risks   and Benefits of Antian-giogenic Therapy for Ovarian Cancer Patients, was held throughout the United States from October 2014 to April 2015. The questions asked by participants during these activities were collected, compiled, and categorized (see Figure 1 below). The questions high-light several areas of clinical focus in the treatment of ovarian cancer and will be addressed as part of this brief analysis......

Planning and Reporting of Quality of Life Outcomes in Cancer Trials

abstract

 First published online: June 30, 2015

 Background Information about the impact of cancer treatments on patients' quality of life (QoL) is of paramount importance to patients and treating oncologists. Cancer trials that do not specify QoL as an outcome or fail to report collected QoL data, omit crucial information for decision making. To estimate the magnitude of these problems, we investigated how frequently QoL outcomes were specified in protocols of cancer trials and subsequently reported. 

Design Retrospective cohort study of RCT protocols approved by six research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003.

Altruism is simpler than we thought

medical news

 Researchers find that a simple computational model of altruism, where specific brain regions represent other's needs, can predict when people are generous and why generosity sometimes feels so difficult......
 
 -----------------------------------------------------------------------------------------

research article - open access 
 A Neurocomputational Model of Altruistic Choice and Its Implications

Introduction

Altruism involves helping others at a cost to the self, not only when such behavior is supported by strategic considerations like reciprocity or cooperation....

Robotic surgery for ovarian cancers: individualization of the surgical approach to select ovarian cancer patients

abstract 
 

BACKGROUND:

While well-accepted treatment for endometrial and cervical cancers, the role of robotic surgery in the management of primary and recurrent ovarian cancers remains an area of active study and debate.

METHODS:

Narrative review of the pertinent literature on the use of robotics in the treatment of ovarian cancers.

RESULTS:

The available evidence may indicate the feasibility of robotics for primary and secondary debulking of ovarian cancers. The use of robotics can be considered for the surgical treatment of patients requiring primary tumour excision, alone or with one additional major procedure, and patients with isolated recurrences. However, most of the publications are underpowered, retrospective, fail to provide sufficient data on long-term oncological outcomes and are published by highly skilled minimally invasive surgeons.

CONCLUSIONS: 

Robot-assisted surgery may provide a tool to individualize the surgical approach to select ovarian cancer patients.

Laparoscopic Salpingo-oophorectomy in Conscious Sedation

abstract

 Journal of the Society of Laparoendoscopic Surgeons / Society of Laparoendoscopic Surgeons

INTRODUCTION:

Conscious sedation has traditionally been used for laparoscopic tubal ligation. General anesthesia with endotracheal intubation may be associated with side effects, such as nausea, vomiting, cough, and dizziness, whereas sedation offers the advantage of having the patient awake and breathing spontaneously. Until now, only diagnostic laparoscopy and minor surgical procedures have been performed in patients under conscious sedation.

CASE DESCRIPTION:

Our report describes 5 cases of laparoscopic salpingo-oophorectomy successfully performed with the aid of conventional-diameter multifunctional instruments in patients under local anesthesia. Totally intravenous sedation was provided by the continuous infusion of propofol and remifentanil, administered through a workstation that uses pharmacokinetic-pharmacodynamic models to titrate each drug, as well as monitoring tools for levels of conscious sedation and local anesthesia. We have labelled our current procedure with the acronym OLICS (Operative Laparoscopy in Conscious Sedation). Four of the patients had mono- or bilateral ovarian cysts and 1 patient, with the BRCA1 gene mutation and a family history of ovarian cancer, had normal ovaries. Insufflation time ranged from 19 to 25 minutes. All patients maintained spontaneous breathing throughout the surgical procedure, and no episodes of hypotension or bradycardia occurred. Optimal pain control was obtained in all cases. During the hospital stay, the patients did not need further analgesic drugs. All the women reported high or very high satisfaction and were discharged within 18 hours of the procedure.

DISCUSSION AND CONCLUSION:

Salpingo-oophorectomy in conscious sedation is safe and feasible and avoids the complications of general anesthesia. It can be offered to well-motivated patients without a history of pelvic surgery and low to normal body mass index.

Harnessing Pandemonium: The Clinical Implications of Tumor Heterogeneity in Ovarian Cancer

open access

 CONTENTS

• Abstract
• Background
• Tracking Heterogeneity in Epithelial Ovarian Cancer – The Precursor Lesion
• Heterogeneity in Ovarian Cancer
• Clinical Implications of Tumor Heterogeneity in Ovarian Cancer
• Conclusion and Future Directions

Centralisation of epithelial ovarian cancer surgery: results on survival from a peripheral teaching hospital. - PubMed - NCBI

abstract

OBJECTIVE:

The objective of this retrospective descriptive study was to assess overall survival and disease free survival of patients treated for epithelial ovarian cancer by a gynaecologic-oncologist in a single Dutch peripheral teaching hospital and to identify independent prognostic factors.

STUDY DESIGN:

A retrospective series of 242 patients treated for epithelial ovarian cancer between 1999 and 2011 at Meander Medical Centre was reviewed. Data on patient, tumour and treatment characteristics were collected. Outcomes were overall survival and progression free survival. Data were analysed using the Kaplan-Meier method, log-rank test and Cox regression analysis.

RESULTS:

Median follow-up was 35 months (range 1-203). Staging procedures were performed in 81 patients of which 63% were complete. 61% of patients had advanced stage disease. In 46%, debulking surgery was complete. Five-year overall survival and progression free survival for all patients was 52% and 47%, respectively. Multivariate analysis identified performance status [HR=1.89 and 1.92 for performance status 2, HR=7.01 and 2.69 for performance status 3], FIGO stage [HR=3.59 for stage II, HR=5.43 and 5.64 for stage III, HR=12.17 and 10.21 for stage IV] and residual disease after debulking surgery [HR=2.01 and 1.72 for incomplete debulking] as independent prognostic factors for overall survival and progression free survival respectively.

CONCLUSION:

Survival after surgery for epithelial ovarian cancer in this cohort is comparable to survival in centralised clinics presented in literature. Partial concentration of cancer care by recruitment of specialised gynaecologic-oncologists in teaching hospitals might be an alternative to complete centralisation of epithelial ovarian cancer treatment in larger cancer centres.

The National Clinical Trials Network: Conducting Successful Clinical Trials of New Therapies for Rare Cancers - Seminars in Oncology

abstract

 Rare cancers account for 27% of neoplasms diagnosed each year, and 25% of cancer-related deaths in the United States. However, rare cancers show some of the highest response rates to targeted therapies, probably due to identification of oncogenic drivers with little inter-patient variability. Although the low incidence of rare cancers make large scale randomized trials involving single histologies difficult to perform, drugs have been successfully developed in rare cancers utilizing clinical trial designs that combine microscopic anatomies. Such trials are being pursued within the National Clinical Trials Network (NCTN), which possesses unique qualifications to perform widespread molecular screening of tumors for patient enrollment onto therapeutic clinical trials. When larger clinical trials are needed to determine optimum treatment strategies in rare cancers, the NCTN’s broad reach in North America and internationally, and ability to partner with both US-based and international research organizations, can make these challenging studies feasible.

Genetic Testing and Tissue Banking for Personalized Oncology: Analytical and Institutional Factors

abstract

 Personalized oncology, or more aptly precision oncogenomics, refers to the identification and implementation of clinically actionable targets tailored to an individual patient’s cancer genomic information. Banking of human tissue and other biospecimens establishes a framework to extract and collect the data essential to our understanding of disease pathogenesis and treatment. Cancer cooperative groups in the United States have led the way in establishing robust biospecimen collection mechanisms to facilitate translational research, and combined with technological advances in molecular testing, tissue banking has expanded from its traditional base in academic research and is assuming an increasingly pivotal role in directing the clinical care of cancer patients. Comprehensive screening of tumors by DNA sequencing and the ability to mine and interpret these large data sets from well-organized tissue banks have defined molecular subtypes of cancer. Such stratification by genomic criteria has revolutionized our perspectives on cancer diagnosis and treatment, offering insight into prognosis, progression, and susceptibility or resistance to known therapeutic agents. In turn, this has enabled clinicians to offer treatments tailored to patients that can greatly improve their chances of survival. Unique challenges and opportunities accompany the rapidly evolving interplay between tissue banking and genomic sequencing, and are the driving forces underlying the revolution in precision medicine. Molecular testing and precision medicine clinical trials are now becoming the major thrust behind the cooperative groups’ clinical research efforts.

Peri-operative Management of Heparin-Induced Thrombocytopenia Syndrome in a Patient With a Suspected Gyn Malignancy

open access-case report

 At times we encounter clinical problems for which there are no directly applicable evidence-based solutions, but we are compelled by circumstances to act. When doing so we rely on related evidence, general principles of best medical practice, and our experience. Each “Current Clinical Practice” feature article in Seminars in Oncology describes such a challenging presentation and offers treatment approaches from selected specialists.....

For younger women | Target Ovarian Cancer

For younger women

Pan-cancer analysis of TCGA data reveals notable signaling pathways

Full text 


" The second interesting relationship is that the Calcium pathway hardly overlaps with the other six pathways. This is shown in Fig. 1b. The Calcium pathway was found to be notable in only ovarian and uterine cancer (Table 1). This result indicates that there might be a common region of aberrant signaling in these two cancers, which does not overlap with regions of aberrant signaling in other cancers."

Background

A signal transduction pathway (STP) is a network of intercellular information flow initiated when extracellular signaling molecules bind to cell-surface receptors. Many aberrant STPs have been associated with various cancers. To develop optimal treatments for cancer patients, it is important to discover which STPs are implicated in a cancer or cancer-subtype. The Cancer Genome Atlas (TCGA) makes available gene expression level data on cases and controls in ten different types of cancer including breast cancer, colon adenocarcinoma, glioblastoma, kidney renal papillary cell carcinoma, low grade glioma, lung adenocarcinoma, lung squamous cell carcinoma, ovarian carcinoma, rectum adenocarcinoma, and uterine corpus endometriod carcinoma.

Indicators of integration of oncology and palliative care programs: an international consensus

abstract

Background Recently, the concept of integrating oncology and palliative care has gained wide professional and scientific support; however, a global consensus on what constitutes integration is unavailable. We conducted a Delphi Survey to develop a consensus list of indicators on integration of specialty palliative care and oncology programs for advanced cancer patients in hospitals with ≥100 beds.

2007 Survivors' Debate: The Past Decade in Ovarian Cancer Dedicated to: Carolyn Benivegn

Slides (pdf format)

  "Our lives begin to end the day we become silent about things that matter.”

Martin Luther King, Jr.

2009 (article) Hope with More: In Their Own (Ovarian Cancer) Words

Hope with More

Hope with More ‘In  Their Own (Ovarian Cancer) Words’©

September 11th , 2009
Author:  Sandi Pniauskas

Chronic inflammation: is it the driver or is it paving the road for malignant transformation?

open access

ABSTRACT

Chronic inflammation in well-defined mouse models such as Giα2 knock out mouse has been shown to trigger formation and expansion of hypoxic niches and also leads to up regulation of NFĸB, offering cells which have adapted their genetic machinery to hypoxia a unique survival advantage. These adapted cells have been shown to acquire stem cell-like capabilities as shown by up regulation of stem cell markers. Such long lived cells become permanent residents in sub mucosa and acquire a malignant phenotype from long-term exposure to noxious environmental agents due to a barrier defect secondary to down regulation of barrier proteins such as Zo1 and Occludin. Indeed mitotic spindle disorientation in such mice has been proposed as another contributory factor to malignant transformation. Sterilization of bowel lumen of these mice through different techniques has prevented malignant transformation in the presence of chronic inflammation. These facts stand strongly against chronic inflammation as a true driver of carcinogenesis but clearly support its role in facilitating the emergence of the neoplastic clone.

The gynecological surveillance of women with Lynch syndrome in Sweden - Gynecologic Oncology

abstract
 

Objective

: Women with Lynch syndrome (LS) have up to a 60% lifetime risk of endometrial cancer (EC) and up to a 24% risk of ovarian cancer (OC). Gynecological surveillance is recommended, but the benefit and how it should be performed remain unclear. The purpose of this study was to assess diagnostic modalities for gynecological screening of LS patients in Sweden and clinical outcome.

Methods

: A retrospective nationwide study of 170 women with molecularly confirmed LS. Data including gynecological LS screening history, biopsy results (if any), genetic records, number of screening visits, results from screening including transvaginal ultrasound (TVUS), endometrial biopsy (EB), blood test for tumor marker cancer antigen (CA) 125, prophylactic surgery including age at procedure, and setting from which screening data were obtained from medical records.

Results

: A total of 117 women were eligible for gynecological screening and of these, 86 patients attended screening visits. Of these, 41 underwent prophylactic hysterectomy and/or bilateral salpingo-oophorectomy. Two patients (4.9%) were diagnosed with EC and two (4.9%) with precancerous lesions in conjunction with prophylactic surgery. Total incidence of gynecological cancer in the surveillance group (45 women) was 20% EC, 4% OC. Five patients had endometrial cancer or complex hyperplasia with atypia (n = 2) detected by endometrial biopsy. Four additional cases were detected due to interval bleeding. Both cases of ovarian cancer were detected by transvaginal ultrasound in patients with ovarian cysts under surveillance. The youngest woman with endometrial cancer was diagnosed at 35 years of age, before she was aware of her diagnosis of Lynch syndrome.

Call for Nominations: Pan-Canadian Oncology Drug Review deadline July 31st

Home 

Call for Nominations Background The role of the pCODR Expert Review Committee (pERC) is to assess the clinical evidence and cost-effectiveness of cancer drugs in order to make recommendations to the provinces and territories to help guide their drug funding decisions. Composed of up to 16 members, pERC makes recommendations and provides advice to the Ministries of Health and cancer agencies. Patient Member pERC is looking for a Patient Member who has first-hand experience with the treatment and care of cancer or is the family member of a cancer patient and has developed a deep understanding of the treatment and care of cancer. Desired Qualifications The successful candidate will have personal knowledge of, experience with, and understanding of issues related to cancer and its management (diagnosis, treatment, and care).  They will also have a demonstrated understanding and appreciation of patient needs and priorities and an overall understanding of other patient issues and health care concerns that may impact cancer patient communities.     Successful candidates should also possess the following: Strong communication and interpersonal skills to be able to work constructively as a member of a team Ability to act with integrity and independence  from specific interests and gain respect and credibility within a diverse range of stakeholders Open-minded approach and diplomacy skills, with the ability to relate to and respect a diverse range of values and beliefs Members of pERC are expected to prepare for and attend up to 12 meetings per year in Toronto, and comply with pCODR's Conflict of Interest and Confidentiality requirements.  No person currently employed by any pharmaceutical or related company will be considered.  Members of pERC receive a modest remuneration. All applicants will receive confirmation of receipt of their applications.  While we thank all applicants for their submissions, only those under further consideration will be contacted personally. All applications must be received by July 31, 2015. For more information and how to apply, please visit www.hrassociates.ca/cadth-pcodr. To request communication in an accessible format, please contact us at 416.237.1500 (1-866-598-1500) ext.231 or email at pcodr@hrassociates.ca.

Intake of vitamins A, C, and E and folate and the risk of ovarian cancer

abstract
 

Cancer Causes Control. 2015 Jul 14. [Epub ahead of print]

Intake of vitamins A, C, and E and folate and the risk of ovarian cancer in a pooled analysis of 10 cohort studies

 PURPOSE:

Vitamins A, C, and E and folate have anticarcinogenic properties and thus might protect against cancer. Few known modifiable risk factors for ovarian cancer exist. We examined the associations between dietary and total (food and supplemental) vitamin intake and the risk of invasive epithelial ovarian cancer.

METHODS:

The primary data from 10 prospective cohort studies in North America and Europe were analyzed. Vitamin intakes were estimated from validated food frequency questionnaires in each study. Study-specific relative risks (RRs) were estimated using the Cox proportional hazards model and then combined using a random-effects model.

RESULTS:

Among 501,857 women, 1,973 cases of ovarian cancer occurred over a median follow-up period of 7-16 years across studies. Dietary and total intakes of each vitamin were not significantly associated with ovarian cancer risk. The pooled multivariate RRs [95 % confidence intervals (CIs)] for incremental increases in total intake of each vitamin were 1.02 (0.97-1.07) for vitamin A (increment: 1,300 mcg/day), 1.01 (0.99-1.04) for vitamin C (400 mg/day), 1.02 (0.97-1.06) for vitamin E (130 mg/day), and 1.01 (0.96-1.07) for folate (250 mcg/day). Multivitamin use (vs. nonuse) was not associated with ovarian cancer risk (pooled multivariate RR = 1.00, 95 % CI 0.89-1.12). Associations did not vary substantially by study, or by subgroups of the population. Greater vitamin intakes were associated with modestly higher risks of endometrioid tumors (n = 156 cases), but not with other histological types.

CONCLUSION:

These results suggest that consumption of vitamins A, C, and E and folate during adulthood does not play a major role in ovarian cancer risk.

recent pubmed search - related specifically to ovarian cancer

 NCBI

Results: 1 to 20 of 98

Select item 261730021.

p16 As a prognostic indicator in ovarian/ tubal high grade serous carcinoma.

Beirne JP, McArt DG, James JA, Salto-Tellez M, Maxwell P, McCluggage WG.

Histopathology. 2015 Jul 14. doi: 10.1111/his.12777. [Epub ahead of print]

PMID:

26173002

Similar articles

Select item 261725112.

HE4, CA125, the Risk of Malignancy Algorithm and the Risk of Malignancy Index and complex pelvic masses - a prospective comparison in the pre-operative evaluation of pelvic masses in an Australian population.

Richards A, Herbst U, Manalang J, Pather S, Saidi S, Tejada-Berges T, Tan K, Williams P, Carter J.

Aust N Z J Obstet Gynaecol. 2015 Jul 14. doi: 10.1111/ajo.12363. [Epub ahead of print]

PMID:

26172511

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Select item 261723033.

Hyperglycemia-induced metabolic compensation inhibits metformin sensitivity in ovarian cancer.

Litchfield LM, Mukherjee A, Eckert MA, Johnson A, Mills KA, Pan S, Shridhar V, Lengyel E, Romero IL.

Oncotarget. 2015 Jun 19. [Epub ahead of print]

PMID:

26172303

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Select item 261719494.

Occurrence of a non deleterious gene conversion event in the BRCA1 gene.

Tessereau C, Léoné M, Buisson M, Duret L, Sinilnikova OM, Mazoyer S.

Genes Chromosomes Cancer. 2015 Jul 14. doi: 10.1002/gcc.22278. [Epub ahead of print]

PMID:

26171949

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Select item 261712345.

Efficacy of tomato concentrates in mouse models of dyslipidemia and cancer.

Chattopadhyay A, Grijalva V, Hough G, Su F, Mukherjee P, Farias-Eisner R, Anantharamaiah GM, Faull KF, Hwang LH, Navab M, Fogelman AM, Reddy ST.

Pharmacol Res Perspect. 2015 Aug;3(4):e00154. doi: 10.1002/prp2.154. Epub 2015 Jun 24.

PMID:

26171234

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Select item 261710356.

Good survival in a patient with recurrent transitional cell carcinoma of the ovary: A case report of PET-CT for detection and follow-up.

Ma J, Yu L, Wang X, Lou GE.

Oncol Lett. 2015 Jul;10(1):384-386. Epub 2015 May 20.

PMID:

26171035

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Select item 261710307.

Significance of gastrin-releasing peptide in ovarian cancer ES2 cells.

Jia Y, Shi H, Fan D.

Oncol Lett. 2015 Jul;10(1):359-363. Epub 2015 May 20.

PMID:

26171030

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Select item 261709738.

Expression levels of seprase/FAPα and DPPIV/CD26 in epithelial ovarian carcinoma.

Zhang M, Xu L, Wang X, Sun B, Ding J.

Oncol Lett. 2015 Jul;10(1):34-42. Epub 2015 Apr 27.

PMID:

26170973

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Select item 261709719.

SGK3 (CISK) may induce tumor angiogenesis (Hypothesis).

Hou M, Lai Y, He S, He W, Shen H, Ke Z.

Oncol Lett. 2015 Jul;10(1):23-26. Epub 2015 May 6.

PMID:

26170971

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Select item 2617072210.

Endometriosis and ovarian cancer: links, risks, and challenges faced.

Pavone ME, Lyttle BM.

Int J Womens Health. 2015 Jul 1;7:663-72. doi: 10.2147/IJWH.S66824. eCollection 2015. Review.

PMID:

26170722

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Single-port versus conventional multiport access prophylactic laparoscopic bilateral salpingo-oophorectomy in high-risk patients for ovarian cancer: a comparison of surgical outcomes.

Angioni S, Pontis A, Sedda F, Zampetoglou T, Cela V, Mereu L, Litta P.

Onco Targets Ther. 2015 Jun 25;8:1575-80. doi: 10.2147/OTT.S82570. eCollection 2015.

PMID:

26170692

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Phase I dose-escalation study of the multikinase inhibitor lenvatinib in patients with advanced solid tumors and in an expanded cohort of patients with melanoma.

Hong D, Kurzrock R, Wheler JJ, Naing A, Falchook GS, Fu S, Kim KB, Davies MA, Nguyen LM, George GC, Xu L, Shumaker R, Ren M, Mink J, Bedell C, Andresen C, Sachdev P, O'Brien JP, Nemunaitis J.

Clin Cancer Res. 2015 Jul 13. pii: clincanres.3063.2015. [Epub ahead of print]

PMID:

26169970

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Development of Olaparib for BRCA-Deficient Recurrent Epithelial Ovarian Cancer.

Tewari KS, Eskander RN, Monk BJ.

Clin Cancer Res. 2015 Jul 13. pii: clincanres.0088.2015. [Epub ahead of print]

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26169965

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Metabolic signatures differentiate ovarian from colon cancer cell lines.

Halama A, Guerrouahen BS, Pasquier J, Diboun I, Karoly ED, Suhre K, Rafii A.

J Transl Med. 2015 Jul 14;13:223. doi: 10.1186/s12967-015-0576-z.

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26169745

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Intake of vitamins A, C, and E and folate and the risk of ovarian cancer in a pooled analysis of 10 cohort studies.

Koushik A, Wang M, Anderson KE, van den Brandt P, Clendenen TV, Eliassen AH, Freudenheim JL, Genkinger JM, Håkansson N, Marshall JR, McCullough ML, Miller AB, Robien K, Rohan TE, Schairer C, Schouten LJ, Tworoger SS, Wang Y, Wolk A, Zeleniuch-Jacquotte A, Smith-Warner SA.

Cancer Causes Control. 2015 Jul 14. [Epub ahead of print]

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26169298

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Pan-cancer analysis of TCGA data reveals notable signaling pathways.

Neapolitan R, Horvath CM, Jiang X.

BMC Cancer. 2015 Jul 14;15:516. doi: 10.1186/s12885-015-1484-6.

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26169172

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The Safety of Pegylated Liposomal Doxorubicin Plus Irinotecan in Recurrent Ovarian Cancer Patients: A Phase I Trial.

Miyahara D, Ueda T, Katsuda T, Maehara M, Fukagawa S, Miyata K, Nam SO, Kondo H, Miyamoto S.

Anticancer Res. 2015 Aug;35(8):4521-5.

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shRNA Depletion of cIAP1 Sensitizes Human Ovarian Cancer Cells to Anticancer Agent-Induced Apoptosis.

Jin H, Dong YY, Zhang H, Cui Y, Xie K, Lou G.

Oncol Res. 2015;22(3):167-76. doi: 10.3727/096504015X14298122915664.

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26168135

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A weighty problem: metabolic perturbations and the obesity-cancer link.

O'Flanagan CH, Bowers LW, Hursting SD.

Horm Mol Biol Clin Investig. 2015 Jul 9. pii: /j/hmbci.ahead-of-print/hmbci-2015-0022/hmbci-2015-0022.xml. doi: 10.1515/hmbci-2015-0022. [Epub ahead of print]

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26167982

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XCR1 promotes cell growth and migration and is correlated with bone metastasis in non-small cell lung cancer.

Wang T, Han S, Wu Z, Han Z, Yan W, Liu T, Wei H, Song D, Zhou W, Yang X, Xiao J.

Biochem Biophys Res Commun. 2015 Jul 9. pii: S0006-291X(15)30204-7. doi: 10.1016/j.bbrc.2015.06.175. [Epub ahead of print]

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Serving on an Advisory Panel | US Cochrane Center (6 videos)

US Cochrane Center

Serving on an Advisory Panel

     CUE - Consumers United for Evidence-based Healthcare is being asked to refer educated consumer advocates to serve on clinical practice guideline panels now more than ever.  In March, 2011, the Institute of Medicine released its report, Clinical Practice Guidelines We Can Trust.  Standard 3 of this report outlines the expectations for consumer involvement.
NEW

Serving on an Advisory Panel for Patients/Consumers & other StakeholdersCUE is considering starting a series of video "short-shorts" (2-4 minutes long) about serving on advisory panels. These are our first 6 videos. Feedback is welcome!

CUE@jhu.edu

Twitter Genomics chat: Dr Markman July 21st 1 pm EST

Cancer Treatment Centers of America

 Sign Up Today For Our #GenomicsChat

Join CTCA expert Dr. Markman on July 21st at 1 p.m. EST

 

"Join me for a Q&A surrounding the difference between genetics vs. genomics, as well as the pros and cons of genomic testing."

Dr. Maurie Markman
President of Medicine and Science

Have you ever wondered what the difference between genetics and genomics is?
Find out by joining CTCA's President of Medicine and Science, Dr. Maurie Markman, on July 21st at 1 p.m. EST for the #GenomicsChat. Dr. Markman will answer numerous questions about the pros and cons of genomic testing during the chat.

 

 

 

2015 NCCN Guideline Updates: New Recommendations Ovarian Cancer

2015 NCCN Guideline Updates:

 The updated ovarian cancer treatment guidelines recommend the use of two new treatment regimens: a comparatively well-tolerated chemotherapy mixture and a first-in-class targeted therapy.

The first of those—18 weekly doses of paclitaxel at 60 mg/m2 infused over 1 hour followed by carboplatin (AUC = 2) infused over 30 minutes—now receives a category 1 recommendation as a primary chemotherapy regimen or a primary adjuvant therapy regimen for patients diagnosed with stage II to stage IV disease.
It is one of several category-1 options for such patients, but it is a particularly good option for elderly patients.

“Ovarian cancer tends to be a cancer that women develop in their 60s and 70s, and chemotherapy is not as well tolerated by patients in that age bracket as it is by the younger patients with other tumors,” said Robert J. Morgan, MD, co-director of the Gynecological Cancers Program at City of Hope and chairman of the NCCN’s ovarian cancer panel.

“Recent research has shown that this paclitaxel/carboplatin regimen is about as effective as several other alternatives but consistently and significantly less toxic. It should thus make a real difference for older patients or those with poor performance status.”

The other new treatment that appears in the updated guidelines is olaparib (Lynparza), the first poly ADP-ribose polymerase (PARP) inhibitor approved to treat any tumor. The drug is particularly active in tumors with BRCA gene mutations. The new NCCN guidelines list it as a preferred agent in the treatment of platinum-sensitive and platinum-resistant disease when FDA-approved tests show germline BRCA mutations and patients have failed on 3 or more previous regimens.
“There are few targeted therapies that have been shown to be effective in ovarian cancer,” said Morgan. He added that most other changes on this year’s guidelines are semantic improvements designed to clarify older recommendations. “It’s also rare for us to add two new regimens in 1 year, so this really constitutes a pretty exciting update.”

The updated ovarian cancer treatment guidelines recommend the use of two new treatment regimens: a comparatively well-tolerated chemotherapy mixture and a first-in-class targeted therapy.

The first of those—18 weekly doses of paclitaxel at 60 mg/m2 infused over 1 hour followed by carboplatin (AUC = 2) infused over 30 minutes—now receives a category 1 recommendation as a primary chemotherapy regimen or a primary adjuvant therapy regimen for patients diagnosed with stage II to stage IV disease.

It is one of several category-1 options for such patients, but it is a particularly good option for elderly patients.

“Ovarian cancer tends to be a cancer that women develop in their 60s and 70s, and chemotherapy is not as well tolerated by patients in that age bracket as it is by the younger patients with other tumors,” said Robert J. Morgan, MD, co-director of the Gynecological Cancers Program at City of Hope and chairman of the NCCN’s ovarian cancer panel.

“Recent research has shown that this paclitaxel/carboplatin regimen is about as effective as several other alternatives but consistently and significantly less toxic. It should thus make a real difference for older patients or those with poor performance status.”

The other new treatment that appears in the updated guidelines is olaparib (Lynparza), the first poly ADP-ribose polymerase (PARP) inhibitor approved to treat any tumor. The drug is particularly active in tumors with BRCA gene mutations. The new NCCN guidelines list it as a preferred agent in the treatment of platinum-sensitive and platinum-resistant disease when FDA-approved tests show germline BRCA mutations and patients have failed on 3 or more previous regimens.

“There are few targeted therapies that have been shown to be effective in ovarian cancer,” said Morgan. He added that most other changes on this year’s guidelines are semantic improvements designed to clarify older recommendations. “It’s also rare for us to add two new regimens in 1 year, so this really constitutes a pretty exciting update.” - See more at: http://www.onclive.com/publications/obtn/2015/May-2015/2015-nccn-guideline-updates-new-recommendations-for-clinical-practice#sthash.c2B15awL.TmxBvZiX.dpuf

Death Burden & End-of-Life Care Intensity AYA Patients With Cancer

full text Editorial + references JAMA Network

 Editorial | July 09, 2015

The Death Burden and End-of-Life Care Intensity Among Adolescent and Young Adult Patients With Cancer

..... These differences between AYAs and either younger or older patients with cancer are even greater if noninvasive cancer is included because AYAs are the age group with the greatest proportion of noninvasive cancer, in situ, benign, and borderline tumors of the cervix, breast, ovary, and central nervous system....

Cancerism - confronting the biases we share - TED/Youtube (gyn oncologist)

video

 Cancerism -- confronting the biases we share | Rick Boulay, M.D. | TEDxLehighRiver

TEDx Talks

2,560,956

1,227

Published on Nov 12, 2014

 

This talk was given at a local TEDx event, produced independently of the TED Conferences. Our precious time and heartfelt hopes should not be abandoned easily.

Rick Boulay, M.D. | TEDxLehighRiver 

Doctor, Lehigh Valley Health Network

 

Ovarian Cancer and Us blog - ways to access (social media)

  data: total page views    666,930

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Screening for Occult Cancer in Unprovoked Venous Thromboembolism

open access - NEJM

 BACKGROUND

Venous thromboembolism may be the earliest sign of cancer. Currently, there is a
great diversity in practices regarding screening for occult cancer in a person who
has an unprovoked venous thromboembolism. We sought to assess the efficacy of
a screening strategy for occult cancer that included comprehensive tomography (CT) of the abdomen and pelvis in patients who had a first unprovoked
venous thromboembolism......

alternative source (McMaster)/abstract link/comments:
Comments from Clinical Raters

The expression of aldehyde dehydrogenase 1 (ALDH1) in ovarian carcinomas and its clinicopathological associations: a retrospective study

Full text 

Background

Ovarian carcinoma remains the most mortality in gynecologic tumors [1]. There are 225,000 new cases diagnosed and 140,000 deaths of ovarian carcinoma annually worldwide [1]. The standard treatment remains surgery followed by platinum-based chemotherapy [2]. Acquired drug resistance and cancer recurrence become the main hurdles for ovarian carcinoma treatment currently [3]. As a result, new reagents targeting the chemo-resistant cells are needed. 

Aldehyde dehydrogenases (ALDH) are a group of enzymes that catalyse dehydrogenation of aldehydes to their corresponding carboxylic acids. To date, nineteen ALDH genes which encode several isozymes have been identified in human genome.....

Table 2: ALDH1 IHC score in tumor cells			p-value
1 (negative)	2 (low)	3 (high)

Histological subtype:
Serous carcinoma	163	67 (41.1 %)	80 (49.1 %)	16 (9.8 %)
Mucinous carcinoma	18	4 (22.2 %)	3 (16.7 %)	11 (61.1 %)	<0.001
Endometrioid carcinoma	19	4 (21.1 %)	9 (47.4 %)	6 (31.6 %)
Clear cell carcinoma	11	6 (54.5 %)	4 (36.4 %)	1 (9.1 %)
Mixed epithelial tumor	11	2 (18.2 %)	6 (54.5 %)	3 (27.3 %)
Undifferentiated tumor	5	3 (60.0 %)	1 (20.0 %)	1 (20.0 %)
Unclassified tumor and others	21