OVARIAN CANCER and US

Blog Archives: Nov 2004 - present

#ovariancancers



Special items: Ovarian Cancer and Us blog best viewed in Firefox

Search This Blog

Monday, November 18, 2013

Pharmacokinetics and Imaging of 212Pb-TCMC-Trastuzumab After Intraperitoneal Administration in Ovarian Cancer Patients



abstract

Purpose: Study distribution, pharmacokinetics, and safety of intraperitoneal (IP) 212Pb-TCMC-trastuzumab in patients with HER-2-expressing malignancy.

Experimental Design: IP 212Pb-TCMC-trastuzumab was delivered, after 4 mg/kg intravenous (IV) trastuzumab (Herceptin), to 3 patients with HER-2-expressing cancer who had failed standard therapies. Patients were monitored for toxicity and pharmacokinetics/dosimetry parameters.

Results: Imaging studies after 0.2 mCi/m2 (7.4 MBq/m2) show little redistribution out of the peritoneal cavity and no significant uptake in major organs. Peak blood level of the radiolabeled antibody, determined by decay corrected counts, was <23% injected dose at 63 hours; maximum blood radioactivity concentration was 6.3nCi/mL at 18 hours. Cumulative urinary excretion was ≤6% in 2.3 half-lives. The maximum external exposure rate immediately post-infusion at skin contact over the abdomen averaged 7.67 mR/h and dropped to 0.67 mR/h by 24 hours. The exposure rates at the other positions monitored (axilla, chest, and femur) decreased as a function of distance from the abdomen. The data points correlate closely with 212Pb physical decay (T1/2=10.6 hours). Follow-up >6 months showed no evidence of agent-related toxicity.

Conclusions: Pharmacokinetics and imaging after 0.2 mCi/m2 IP 212Pb-TCMC-trastuzumab in patients with HER-2-expressing malignancy showed minimal distribution outside the peritoneal cavity, ≤6% urinary excretion, and good tolerance.
 

Sunday, November 17, 2013

Risk Perception, Worry, and Test Acceptance in Average-Risk Women Undergoing Ovarian Cancer Screening



abstract


Objective

We evaluated baseline knowledge of ovarian cancer risk and perceptions toward ovarian cancer screening (OCS) in women initiating the normal risk ovarian screening study (NROSS).

Study Design

Average-risk, postmenopausal women were enrolled between 2001 and 2011 as they entered the NROSS. Participants completed baseline surveys of risk perception, cancer worry (Cancer Worry Scale), anxiety (State-Trait Anxiety Inventory), health and well-being (SF-36), and acceptability of OCS.

Results

Of the 1242 women enrolled, 925 (74.5%) completed surveys. The respondents estimated a mean lifetime risk of ovarian cancer of 29.9%, much higher than the actual risk of 1.4% for women in the U.S. Only 2.8% of participants correctly estimated their risk, while 35.4% reported their lifetime risk to be ≥50%. Cancer worry was low, with a median CWS score of 7 out of 24. Anxiety was comparable to published norms for women in this age group, with median STAI-S and STAI-T scores of 30 and 29 out of 80, respectively. Overall, women reported good physical and mental well-being. In terms of OCS acceptability, 97.2% of respondents agreed, or strongly agreed, that “the benefits of screening outweigh the difficulties.” Very few women were reluctant to undergo OCS due to time constraints (1.1%), pain (2.0%), or embarrassment (1.9%).

Conclusions

Average-risk women undergoing OCS highly overestimated their risk of ovarian cancer. Despite this, participants reported low cancer worry and anxiety. The discrepancy between knowledge of and attitudes toward ovarian cancer risk highlights the need for educational efforts in this area.


Funding Source: This study was supported by funds from the MD Anderson SPORE in Ovarian Cancer NCI P50 CA83639 and Grant Number T32 CA101642 from the NIH National Research Service Award. Dr. Skates was supported in part by grant CA152990 from NCI's Early Detection Research Network. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCI or NIH.
Presentation Information: This research was presented as a poster at the Society of Gynecologic Oncologists 43rd Annual Meeting on Women’s Cancer in Austin, TX from March 24 – 27, 2012.
 

Saturday, November 16, 2013

Clinician characteristics, communication, and patient outcome in oncology: a systematic review - De Vries - 2013 - Psycho-Oncology - Wiley Online Library



abstract
 

Objective

The aim of this study was to review the literature on clinician characteristics influencing patient–clinician communication or patient outcome in oncology.

Methods

Studies investigating the association of clinician characteristics with quality of communication and with outcome for adult cancer patients were systematically searched in MEDLINE, PSYINFO, PUBMED, EMBASE, CINHAL, Web of Science and The Cochrane Library up to November 2012. We used the preferred reporting items for systematic reviews and meta-analyses statement to guide our review. Articles were extracted independently by two of the authors using predefined criteria.

Results

Twenty seven articles met the inclusion criteria. Clinician characteristics included a variety of sociodemographic, relational, and personal characteristics. A positive impact on quality of communication and/or patient outcome was reported for communication skills training, an external locus of control, empathy, a socioemotional approach, shared decision-making style, higher anxiety, and defensiveness. A negative impact was reported for increased level of fatigue and burnout and expression of worry. Professional experience of clinicians was not related to communication and/or to patient outcome, and divergent results were reported for clinician gender, age, stress, posture, and confidence or self-efficacy.

Conclusions

Various clinician characteristics have different effects on quality of communication and/or patient outcome. Research is needed to investigate the pathways leading to effective communication between clinicians and patients. 

How Cancers Grow [Video]: Scientific American



Video

Metastatic Behavior of Upper Tract Urothelial Carcinoma After Radical Nephroureterectomy: Association with Primary Tumor Location



 Blogger's Note: this abstract does not indicate if Lynch Syndrome patients were included; of interest, especially, in light of the scarcity of research specific to UTUC (of the ureter/renal pelvis)

abstract

PURPOSE:

To investigate the site-specific pattern of disease recurrence and/or metastasis and the associated patient outcomes after radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC).

METHODS:

A total of 733 patients with UTUC from a retrospective multi-institutional cohort were included, with a median follow-up of 34 months. Associated patient outcomes were analyzed by multivariate analysis. To evaluate the influence of primary tumor location, we divided it into four areas: renal pelvis, and upper, middle, and lower ureter.

RESULTS:

A total of 218 patients experienced disease recurrence, with the majority of relapses occurring within the first 3 years. Cumulative incidence rates of first disease recurrence at 1 and 3 years were 18.9 and 29.8 %, respectively. Of these patients, 38.5 % developed distant recurrence; 17.4 % experienced both local and distant recurrences; and 44.0 % developed isolated local recurrence. The predominant sites of distant metastasis were lung, liver, and bone. Multivariate analysis revealed that the prevalence of local recurrence and lung metastasis was significantly associated, with primary tumor location being independent of other clinicopathological variables. Lower/middle ureter tumors had a higher rate of local recurrence in the pelvic cavity, and renal pelvic tumors had a higher prevalence of distant relapse in the lungs. Similar results were obtained when rerunning the data set by excluding patients who received adjuvant chemotherapy (n = 131).

CONCLUSIONS:

This multi-institutional study provided a detailed picture of metastatic behavior after RNU, and primary tumor locations were associated with unique patterns of metastatic spread in UTUC patients.
 

Research findings call for a rethinking of cancer genetics



rethinking 

"....Hardwick says the findings call researchers to greater scrutiny in their genetic analyses because they could unwittingly attribute a phenomenon to a gene they mutated, when it is actually due to a secondary mutation..... 

Vaccine Therapy and IDO1 Inhibitor INCB024360 in Treating Patients With Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Are in Remission



Full Text View 

This study is not yet open for participant recruitment.
Verified November 2013 by Roswell Park Cancer Institute
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT01982487
First received: November 6, 2013
Last updated: NA
Last verified: November 2013
History: No changes posted
 

A Registry for BRCA Mutation Carriers With Pancreatic Ductal Adenocarcinoma



Full Text View

ClinicalTrials.gov Identifier:
NCT01983410
First received: November 4, 2013
Last updated: November 7, 2013
Last verified: November 2013
 

Editorial: Ups and downs of evidence and practice guidelines (plus commentaries Yes/No)




 http://www.cfp.ca/local/img/journal_logo.jpg
Ups and downs

"...With evidence that does not stand the test of time and practice guidelines rife with expert opinions, it’s no wonder that family physicians no longer know what to believe!"



    What Is Wrong With Discharges Against Medical Advice (and How to Fix Them)



    JAMA Network

    "It is estimated that as many as 2% of all US hospital discharges (approximately 500 000 per year) are designated as against medical advice1; that is, a patient chooses to leave the hospital before the treating physician recommends discharge. The risks to these patients are significant. Compared with patients discharged conventionally, readmission rates for patients discharged against medical advice are 20% to 40% higher, and their adjusted relative risk of 30-day mortality may be 10% higher.2 Furthermore, physicians and other health care staff report feeling distressed and powerless when patients choose suboptimal care, and disagreement over a discharge against medical advice can cause patient-physician and intrateam conflict.3

    Although these harms have been well described, the stigmatizing effect on patients of discharges against medical advice has rarely been examined. Compared with how the profession handles clinical disagreements in other settings (eg, outpatient), an “against medical advice” designation is an outdated concept unsupportive of patients. In this Viewpoint, starting from a core value of patient centeredness, we aim to highlight the problematic aspects of discharges against medical advice and suggest a new approach....

    "...Recent studies have highlighted problematic informed consent practices for discharges against medical advice by identifying that a majority of house officers and attending physicians mistakenly believe and inform patients that if they sign out against medical advice, their insurance may not pay for the hospitalization. In a cross-sectional survey of physicians conducted by Schaefer et al,5 85% of residents and 67% of attending physicians reported that they informed patients about denial of insurance payment so that patients would reconsider remaining in the hospital. These studies suggest that the use of misleading information in discharges against medical advice threatens to undermine a patient’s voluntary choice and insinuates that coercion is an acceptable and oft-repeated practice.....
     

    Reflecting on the methodological challenges of recruiting to a United Kingdom-wide, multi-centre, randomised controlled trial in gynaecology outpatient settings



    Trials open access

    Conclusions

    Our article reflects on the methodological challenges of recruiting to a multi-centre RCT in a UK gynaecology setting. Effective interventions included increasing the number of recruiting centres and providing collaborator incentives. Barriers to recruitment included fewer eligible women than anticipated, patient's preference to be allocated to the treatment group, lack of support staff, and variations in approval systems and GP referral procedures. To improve the evidence base on clinical trial recruitment, trialists need to publish their experiences and lessons learned. Future RCTs should evaluate, where possible, the effect of strategies designed to improve recruitment and retention.
    Trial registration: Current Controlled Trials ISRCTN35911035.

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

     

    Biologists ID new cancer weakness (MK2)



    Biologists ID new cancer weakness

    "...While this study focused on non-small-cell lung tumors, the researchers have gotten similar results in cancer cells grown in the lab from bone, cervical, and ovarian tumors. They are now studying mouse models of colon and ovarian cancer.

    Observation of Bevacizumab Plus Front-line Chemotherapy in Patients With Ovarian Cancer



    clinical trial

      V erified by: Hellenic Oncology Research Group, November 2013

    First Received: November 3, 2013 | Last Updated: November 6, 2013
    Phase: N/A | Start Date: March 2012
    Overall Status: Recruiting | Estimated Enrollment: 200

    Cancer risk in systemic lupus: an updated international multi-centre cohort study [J Autoimmun. 2013] - PubMed - NCBI



    abstract

    OBJECTIVE:

    To update estimates of cancer risk in SLE relative to the general population.

    METHODS:

    A multisite international SLE cohort was linked with regional tumor registries. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers.

    RESULTS:

    Across 30 centres, 16,409 patients were observed for 121,283 (average 7.4) person-years. In total, 644 cancers occurred. Some cancers, notably hematologic malignancies, were substantially increased (SIR 3.02, 95% confidence interval, CI, 2.48, 3.63), particularly non-Hodgkin's lymphoma, NHL (SIR 4.39, 95% CI 3.46, 5.49) and leukemia. In addition, increased risks of cancer of the vulva (SIR 3.78, 95% CI 1.52, 7.78), lung (SIR 1.30, 95% CI 1.04, 1.60), thyroid (SIR 1.76, 95% CI 1.13, 2.61) and possibly liver (SIR 1.87, 95% CI 0.97, 3.27) were suggested. However, a decreased risk was estimated for breast (SIR 0.73, 95% CI 0.61-0.88), endometrial (SIR 0.44, 95% CI 0.23-0.77), and possibly ovarian cancers (0.64, 95% CI 0.34-1.10). The variability of comparative rates across different cancers meant that only a small increased risk was estimated across all cancers (SIR 1.14, 95% CI 1.05, 1.23).

    CONCLUSION:

    These data estimate only a small increased risk in SLE (versus the general population) for cancer over-all. However, there is clearly an increased risk of NHL, and cancers of the vulva, lung, thyroid, and possibly liver. It remains unclear to what extent the association with NHL is mediated by innate versus exogenous factors. Similarly, the etiology of the decreased breast, endometrial, and possibly ovarian cancer risk is uncertain, though investigations are ongoing.
     

    Investigating the clinical potential for 14-3-3 zeta protein to serve as a biomarker for epithelial ovarian cancer



    Journal of Ovarian Research open access

     Conclusions

    Determination of CA-125 and HE4 serum levels for the determination of the risk of ovarian malignancy algorithm (ROMA) represents a useful tool for the prediction of chemotherapy efficacy for EOC patients. However, levels of 14-3-3 zeta protein were not found to vary significantly as a consequence of treatment. Therefore we question if 14-3-3 zeta protein is a reliable biomarker, which correlates with the clinical behavior of EOC.

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

     Impact of family history of breast cancer on tumour characteristics, treatment, risk of second cancer and survival among men with breast cancer



    open access

    Introduction

    Breast cancer is the most common cancer among women in most countries, but it is rare in men, accounting for fewer than 1% of all breast cancer cases [1]. Rare germ-line mutations in BRCA1 and BRCA2 are thought to account for between 5% and 10% of all breast cancer cases in unselected populations. Male breast cancer (BC) is more strongly associated with the presence of an inherited BRCA2 mutation than with the presence of a BRCA1 mutation, and the lifetime risks of breast cancer for male mutation carriers are about 7% and 1%, respectively [2]. The scarcity of male BC has resulted in comparatively few epidemiological studies assessing the prevalence of a family history of breast and/or ovarian cancer among male BC patients, and its effect on male BC risks. Population-based studies reported that approximately 20% of men with breast cancer have a positive family history of the disease for at least one-degree relative [35]. Similar to that of breast cancer in women [6], an increased risk of breast cancer in men has been associated with a family history of breast cancer [5]. Several studies reported that male BC patients had a higher risk of developing a second primary cancer, but none of them assessed whether this risk was modified by a positive family history [711].
    In this study, we determined the prevalence of a positive family history of breast/ovary cancer among male BC patients. In addition, we evaluated the impact of family history, tumour characteristics and treatment on second cancer occurrence and overall survival.....

    "....Sites of second cancers were as follows: prostate (one case), lung (one case), tongue (two cases), stomach (one case) and contralateral breast (one case). The time interval between breast cancer diagnosis and date of second cancer varied from 24 months to 11.6 years....
     

    Accuracy of MDCT in the preoperative definition of Peritoneal Cancer Index (PCI) in patients with advanced ovarian cancer who underwent peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC)



    Abstract

    PURPOSE:

    To evaluate the accuracy of MDCT in the preoperative definition of Peritoneal Cancer Index (PCI) in patients with advanced ovarian cancer who underwent a peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC) after neoadjuvant chemotherapy to obtain a pre-surgery prognostic evaluation and a prediction of optimal cytoreduction surgery.

    MATERIALS AND METHODS:

    Pre-HIPEC CT examinations of 43 patients with advanced ovarian cancer after neoadjuvant chemotherapy were analyzed by two radiologists. The PCI was scored according to the Sugarbaker classification, based on lesion size and distribution. The results were compared with macroscopic and histologic data after peritonectomy and HIPEC. To evaluate the accuracy of MDCT to detect and localize peritoneal carcinomatosis, both patient-level and regional-level analyses were conducted. A correlation between PCI CT and histologic values for each patient was searched according to the PCI grading.

    RESULTS:

    Considering the patient-level analysis, CT shows a sensitivity, specificity, PPV, NPV, and an accuracy in detecting the peritoneal carcinomatosis of 100 %, 40 %, 93 % 100 %, and 93 %, respectively. Considering the regional level analysis, a sensitivity, specificity, PPV, NPV, and diagnostic accuracy of 72 %, 80 %, 66 %, 84 %, and 77 %, respectively were obtained for the correlation between CT and histology.

    CONCLUSION:

    Our results encourage the use of MDCT as the only technique sufficient to select patients with peritoneal carcinomatosis for cytoreductive surgery and HIPEC on the condition that a CT examination will be performed using a dedicated protocol optimized to detect minimal peritoneal disease and CT images will be analyzed by an experienced reader.
     

    High HMGA2 expression and high body mass index negatively affect the prognosis of patients with ovarian cancer



    abstract

    HMGA2 is a small, non-histone, chromatin-associated protein with a key role in tumorigenesis and adipogenesis. Indeed, HMGA2 overexpression has been frequently detected in several malignant neoplasms and inhibition of its expression prevents thyroid cell transformation. Moreover, HMGA2 null mice show a pigmy phenotype with a great reduction in fat tissue. To investigate whether HMGA2 expression correlates with clinico-pathological parameters and patient outcome, immunohistochemical analysis of HMGA2 expression was performed in ovarian cancer specimens from 117 patients. HMGA2 overexpression was found in 39% of the cases and, interestingly, positively correlated with the body mass index (BMI). Moreover, high BMI (≥ 25 kg/m(2) ) and high HMGA2 expression/BMI combined evaluation predicted shorter disease-free survival. High BMI (≥ 25 kg/m(2) ), high expression of HMGA2 and high HMGA2 expression/BMI combined evaluation predicted shorter overall survival. In multivariate analysis, the concomitant high expression of HMGA2 and high BMI (≥ 25 kg/m(2) ) was an independent prognostic factor. Finally, the BMI (≥ 25 kg/m(2) ) negatively correlated with the patient response to chemotherapy (P=0.039). Therefore, the data reported herein suggest that the combined evaluation of HMGA2 expression and obesity assessed through BMI can be considered a marker of poor prognosis in patients affected by ovarian carcinoma 

    Mixed-polarization phenotype of ascites-associated macrophages in human ovarian carcinoma: Correlation of CD163 expression, cytokine levels and early relapse



    abstract


    Ovarian cancer is typically accompanied by the occurrence of malignant ascites containing large number of macrophages. It has been suggested that these tumor-associated macrophages (TAMs) are skewed to alternative polarization (M2) and thereby play an essential role in therapy resistance and metastatic spread. In our study, we have investigated the nature, regulation and clinical correlations of TAM polarization in serous ovarian cancer. Macrophage polarization markers on TAMs and ascites cytokine levels were analyzed for 30 patients and associated with relapse-free survival (RFS) in a prospective study with 20 evaluable patients. Surface expression of the M2 marker CD163 on TAMs was inversely associated with RFS (p < 0.01). However, global gene expression profiles determined for 17 of these patients revealed a mixed-polarization phenotype unrelated to the M1/M2 classification. CD163 surface expression also correlated with the ascites levels of IL-6 and IL-10 (p < 0.05), both cytokines induced CD163 expression, and their ascites levels showed a clear inverse association with RFS (p < 0.01). These findings define a subgroup of patients with high CD163 expression, high IL-6 and/or IL-10 levels and poor clinical outcome.
     

    Genetic, epigenetic and stem cell alteration in endometriosis: new insights and potential therapeutic perspectives



    abstract

    Human endometrium is a highly dynamic tissue, undergoing periodic growth and regression at each menstrual cycle. Endometriosis is a frequent chronic pathological status characterized by endometrial tissue with an ectopic localization, causing pelvic pain and infertility and a variable clinical presentation. In addition, there is well-established evidence that, although endometriosis is considered benign, it is associated with an increased risk of malignant transformation in approximately 1.0% of affected women, with the involvement of multiple pathways of development. Increasing evidence supports a key contribution of different stem/progenitor cell populations not only in the cyclic regeneration of eutopic endometrium, but also in the pathogenesis of at least some types of endometriosis. Evidence has arisen from experiments in animal models of disease through different kinds of assays (including clonogenicity, the label-retaining cell approach, the analysis of undifferentiation markers), as well as from descriptive studies on ectopic and eutopic tissue samples harvested from affected women. Changes in stem cell populations in endometriotic lesions are associated with genetic and epigenetic alterations, including imbalance of miRNA expression, histone and DNA modifications and chromosomal aberrations. The present short review mainly summarizes the latest observations contributing to the current knowledge regarding the presence and the potential contribution of stem/progenitor cells in eutopic endometrium and the aetiology of endometriosis, together with a report of the most recently identified genetic and epigenetic alterations in endometriosis. We also describe the potential advantages of single cell molecular profiling in endometrium and in endometriotic lesions. All these data can have clinical implications and provide a basis for new potential therapeutic applications.
     

    Microbiological quality and characteristics of probiotic products in China



    abstract

    Source

    State Key Laboratory of Food Science and Technology, Nanchang University, Jiangxi, 330047, China; Penn Ovarian Cancer Research Center, Center for Research on Reproduction and Women's Health (CRRWH), Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA, 19104, USA; Institute of Translational Medicine, Nanchang University, People's Republic of China, 999 Xuefu Rd, Honggu District, Nanchang, China.


    BACKGROUND:

    Probiotics are widely used in the food industry and medicine fields in China, but few studies have been conducted to evaluate the actual microbial amounts and species in probiotic products, which may conflict with the labels and mislead consumers to choose inappropriate foods or medicines.

    RESULTS:

    Twenty commercial dairy products and eight commercial 'healthcare' samples were collected from markets in China and tested using culture-dependent and culture-independent methods. The results suggested that the total bacterial counts of most commercial products met the minimum quantitative requirement of the Chinese national standard (6.00 log colony-forming units g(-1) ). However, the bacterial counts of specific species were inconsistent with the labelling. In parallel, denaturing gradient gel electrophoresis analysis indicated that some probiotic-containing products were wrongly labelled; no Bifidobacterium species were detected in the products claiming to contain bifidobacteria, and the probiotic characteristics (antimicrobial activity, acid resistance and bile resistance) of some isolates had degraded. Moreover, some contaminating bacteria, e.g. Enterobacter sp., Klebsiella sp. and Serratia sp., were also detected in these products.

    CONCLUSION:

    The combination of culture-dependent and culture-independent methods was proven to quickly and conveniently detect the microbial diversity in probiotic products, and more effort is required to regulate the probiotic market in China
     

    Clinical ovarian cancers display extensive genetic heterogeneity, study suggests multiple treatment



    Science Codex

    "The divergence of mutation profiles within tumors from individual women suggests that sequencing of multiple samples from a single patient may be necessary before a drug treatment protocol can be devised," said Paul Billings, Chief Medical Officer for Life Technologies. "Very different evolutionary pathways for each woman were observed in the study, which would have been missed if only one section of the primary tumor or just one of the metastatic lesions had been sequenced. The data suggest that if only one metastasis were to be biopsied and sequenced, a number of relevant driver mutations and druggable targets would likely be missed, which would be expected to lead to poor treatment outcomes." 

    Voices: Negotiating the pelvic exam | SGO



    Negotiating the pelvic exam 

    SGO: 2014 Registration and housing for Annual Meeting now open



    SGO

    Registration and housing is currently open for the SGO 45th Annual Meeting on Women’s Cancer in Tampa, FL, March 22 – 25, 2014. A preliminary schedule is also available online.
     

    Ovarian Cancer Clinical Trial Endpoints: Society of Gynecologic Oncology White Paper



    abstract


    Highlights

    Ovarian cancer has unique considerations for clinical trial endpoint selection
    Optimal endpoint selection should reflect true patient benefit
    PFS as a surrogate has significant advantages and disadvantages in ovarian cancer


    Clinical trial endpoints have profound effects on late phase clinical trial design, results interpretation, drug development, and regulatory approval of therapeutics. Selection of the optimal clinical trial endpoint is particularly provocative in ovarian cancer where long overall survival (OS) is observed even for those who present with advanced disease stages. The lack of new regulatory approvals and the lack of harmony between regulatory bodies globally for ovarian cancer therapeutics are of concern. The advantages and disadvantages of the numerous endpoints available are herein discussed within the unique context of ovarian cancer where both crossover and post-progression therapies potentially uncouple the surrogacy between progression-free survival (PFS) and OS, the two most widely supported and utilized endpoints. The roles of patient reported outcomes (PRO) and health related quality of life (HRQoL) are discussed, but even these widely supported parameters are affected by the unique characteristics of ovarian cancer where a significant percentage of patients may be asymptomatic. Original data regarding the endpoint preferences of ovarian cancer advocates is presented.

    Endpoint selection in ovarian cancer clinical trials should reflect the impact on disease burden and unique characteristics of the treatment cohort while reflecting true patient benefit. Both OS and PFS have led to regulatory approvals and are clinically important. However, current regulatory approval guidance by the FDA indicates that surrogates for overall survival, while acceptable, must be clinically meaningful. OS remains the most objective and accepted endpoint because it is least vulnerable to bias; however, the feasibility of OS in ovarian cancer is compromised by the requirement for large trial size, prolonged time-line for final analysis, and potential for unintended loss of treatment effect from active post-progression therapies. A large magnitude of effect in PFS improvement should establish benefit, and further communication with regulatory authorities to clarify acceptable endpoints should be undertaken.
     

    Synergistic inhibition of ovarian cancer cell growth by combining selective PI3K/mTOR and RAS/ERK pathway inhibitors



    abstract


    Background

    Ovarian cancer is the major cause of death from gynaecological malignancy with a 5 year survival of only ∼30% due to resistance to platinum and paclitaxel-based first line therapy. Dysregulation of the phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR) and RAS/extracellular signal-regulated kinase (ERK) pathways is common in ovarian cancer, providing potential new targets for 2nd line therapy.

    Methods

    We determined the inhibition of proliferation of an extensive panel of ovarian cancer cell lines, encompassing all the major histotypes, by the dual PI3K/mTOR inhibitor PF-04691502 and a MEK inhibitor, PD-0325901. In addition, we analysed global gene expression, mutation status of key PI3K/mTOR and RAS/ERK pathway members and pathway activation to identify predictors of drug response.

    Conclusions

    These studies identify dual targeted inhibitors of PI3K/mTOR in combination with inhibitors of RAS/ERK signalling as a potentially effective new approach to treating ovarian cancer.
     

    Oct 29, 2013: First-year progress in MD Anderson's Moon Shots Program



    video

    Description:The University of Texas MD Anderson Cancer Center in September 2012 announced its Moon Shots Program, an unprecedented effort to dramatically accelerate the pace of converting scientific discoveries into clinical advances that reduce cancer deaths. The program initially targets acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS); chronic lymphocytic leukemia (CLL); lung cancer; melanoma; prostate cancer; and triple-negative breast and high-grade serious ovarian cancers. Elizabeth Grimm, Ph.D., interim director and chief scientific officer for MD Anderson's Moon Shots Program, discusses progress since the effort launched one year ago.  

    ICON7 Trial Update - Dr. Amit Oza



    video

      Dr. Amit Oza with an update from ECC 2013 on the final overall survival results in the GCIG phase III randomized trial of bevacizumab in women with newly diagnosed ovarian cancer.

    Public reporting of surgeon outcomes: low numbers of procedures lead to false complacency



    The Lancet

    Summary

    The English National Health Service published outcome information for individual surgeons for ten specialties in June, 2013. We looked at whether individual surgeons do sufficient numbers of procedures to be able to reliably identify those with poor performance. For some specialties, the number of procedures that a surgeon does each year is low and, as a result, the chance of identifying a surgeon with increased mortality rates is also low. Therefore, public reporting of individual surgeons' outcomes could lead to false complacency. We recommend use of outcomes that are fairly frequent, considering the hospital as the unit of reporting when numbers are low, and avoiding interpretation of no evidence of poor performance as evidence of acceptable performance.
     

    When the Doctor Disappears



    NYTimes.com

    Future Oncology - selected abstracts - ovarian cancer (repost)



    Future Oncology - Vol. 9
     December 2013, Vol. 9, No. 12s, Pages 1-1

    Foreword


     Trabectedin plus pegylated liposomal doxorubicin: the return of a treatment option for ovarian cancer

    Future Oncology, December 2013, Vol. 9, No. 12s, Pages 1-1.
    Citation | Full Text | PDF (197 KB) | PDF Plus(198 KB)   | Reprints & Permissions

    Symposium Paper


    Introduction: 1 year of silence?
    ,
    Future Oncology, December 2013, Vol. 9, No. 12s, Pages 3-3.
    Citation | Full Text | PDF (221 KB) | PDF Plus(222 KB)   | Reprints & Permissions

    Trabectedin mechanism of action: what’s new?

    Future Oncology, December 2013, Vol. 9, No. 12s, Pages 5-10.
    Summary | Full Text | PDF (1476 KB) | PDF Plus(1477 KB)   | Reprints & Permissions

    Biology of ovarian cancer and trabectedin mechanism of action

    Future Oncology, December 2013, Vol. 9, No. 12s, Pages 11-17.
    Summary | Full Text | PDF (1472 KB) | PDF Plus(1473 KB)   | Reprints & Permissions

    Optimizing treatment of the partially platinum-sensitive ovarian cancer patient

    Future Oncology, December 2013, Vol. 9, No. 12s, Pages 19-23.
    Summary | Full Text | PDF (493 KB) | PDF Plus(494 KB)   | Reprints & Permissions

    Discussion: session 1
    , ,
    Future Oncology, December 2013, Vol. 9, No. 12s, Pages 25-27.
    Citation | Full Text | PDF (367 KB) | PDF Plus(367 KB)   | Reprints & Permissions

    Increasing the chances for platinum-sensitive ovarian cancer patients

    Future Oncology, December 2013, Vol. 9, No. 12s, Pages 29-35.
    Summary | Full Text | PDF (946 KB) | PDF Plus(947 KB)   | Reprints & Permissions


     

    Thursday, November 14, 2013

    Simplified staging laparotomy in FIGO stage 1 epithelial ovarian cancer: Follow-up and outcomes in South Wales, UK



    abstract


    We have conducted a retrospective analysis of FIGO stage 1 ovarian cancer patients in South Wales, who underwent a simplified staging laparotomy without routine nodal sampling and peritoneal biopsies. Patient records from January 2004 to December 2010 were analysed. A total of 116 patients were included in the final analysis. Adjuvant chemotherapy was offered to patients with risk factors for relapse (grade > 1, clear cell histology, or stage > Ia); overall, 89 patients (76.7%) received adjuvant single agent carboplatin (n = 54, 46.5%) or combination chemotherapy (n = 35, 30.2%). After a median follow up of 41 months (range 12-95), 18 patients have relapsed (15.5%), of these 17 had risk factors and 16 had received adjuvant chemotherapy. Eighteen patients have died, of whom 6 of non-cancer related causes without prior relapse. 5-year overall and relapse free survival were 80%.
    In conclusion, in situations where there are limited resources and operating time constraints, our data suggest that a simplified staging laparotomy approach may be a reasonable compromise in apparently early stage ovarian cancer: this may result in a more aggressive use of chemotherapy, but survival outcomes seem comparable to other series.
     

    Wednesday, November 13, 2013

    request to participate in a survey: Risks, Triggers, and Protective Factors Related to the Expression of Ovarian Cancer



    survey and request:

    My name is Dr. Sandra Cesario and I am on the faculty in the College of Nursing at Texas Woman’s University in Houston, Texas.  Almost 40 years experience as a women’s health nurse and losing a 29-year old daughter to ovarian cancer have led me on a path of research about the risk factors for ovarian cancer.

    The purpose of the proposed project titled Risks, Triggers, and Protective Factors Related to the Expression of Ovarian Cancer, is to collect information from women who have been diagnosed with ovarian cancer, as well as women who do not have the disease, to determine if there is clustering of risk or protective factors that increase or decrease a woman’s chances of developing ovarian cancer.  The research question to be addressed is: What is the constellation of factors that predisposes a woman to be at increased risk for developing ovarian cancer?

    I am requesting your assistance in recruiting participants for this study.  As a support group leader or ListServ monitor, you are likely to be in contact with ovarian cancer survivors and their families who may be interested in completing this anonymous online survey.  Study participation is completely voluntary and women are free to discontinue their participation at any time.  I am primarily seeking English-speaking women, over the age of 18, who have been diagnosed with ovarian cancer. However, ALL women, with or without cancer, are welcome to complete the survey.  This study has been approved by the Institutional Review Board (IRB) of Texas Woman’s University in Houston.
    Would you be willing to post the url for the internet survey on your website, include it in your newsletter, distribute to your email list, and/or offer the opportunity to women at your next in-person contact?
    If so, please advise the women to click on the following link (or copy and paste it into your web browser)
    <https://www.psychdata.com/s.asp?SID=156174>https://www.psychdata.com/s.asp?SID=156174
    to complete the survey via the secure PsychData system. It is estimated that the survey can be completed in 20-25 minutes.

    An email address developed specifically for this study has been created if you have additional questions.
    Cesario-Research@hotmail.com<mailto:Cesario-Research@hotmail.com>
    I value your time and interest in this topic. If you make the decision to participate, thank you very much for your input that is crucial to the outcome of this study.

    Sincerely,

    Dr. Sandra K. Cesario
    PhD Program Coordinator and Professor
    College of Nursing, Texas Woman’s University
    6700 Fannin Street
    Houston, TX  77030-2367
    Office Phone:    713-794-2110

     

    Access, Affordability, and Insurance Complexity Are Often Worse in the United States Compared to 10 Other Countries - The Commonwealth Fund



    open access

    About the Study

    Approximately 20,000 adults in Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, the U.K., and the U.S. were surveyed between February and June 2013. The survey focused on people’s experiences with their country’s health care system, particularly those related to accessing and affording health care.

    Downloads


      Click to download chart as a PowerPoint Slide

    Commentary: Addressing the American Health-Care Cost Crisis: Role of the Oncology Community



    Abstract

    Health-care cost growth is unsustainable, and the current level of spending is harming our economy and our patients. This commentary describes the scope of the health-care spending problem and the particular factors in cancer care that contribute to the problem, reflecting in part presentations and discussions from an Institute of Medicine National Cancer Policy Forum Workshop held in October 2012. Presenters at the workshop identified a number of steps that the oncology community can take to reduce the rate of growth in cancer-care costs while maintaining or improving upon the quality of care. This commentary aims to highlight opportunities for the oncology community to take a leadership role in delivering affordable, high-quality cancer care.

    Related articles

     

    Editorial: The Imperative to Address the Cost of Oncology Care



    open access

    Family History and BRCA1/BRCA2 Status Among Japanese Ovarian Cancer Patients and Occult Cancer in a BRCA1 Mutant Case (BRCA/Lynch Syndrome)



    abstract

    BACKGROUND:

    This study aimed to examine family history among Japanese ovarian cancer patients and to investigate the TP53 status of fallopian tube epithelial and ovarian cancer cells in a Japanese BRCA1 mutant case that may be associated with the transformed state in hereditary ovarian cancer.

    METHODS:

    One hundred and two primary ovarian cancer patients were retrospectively evaluated in this cross-sectional study. The family history of cancer was determined in probands. In a BRCA1 mutant case, p53 immunostaining and direct sequencing, followed by laser-capture microdissection, were performed for the fallopian tube, considered the origin of ovarian cancer.

    RESULTS:

    Nine of 102 (8.8%) families were regarded as having hereditary breast-ovarian cancer syndrome, two families (2.0%) were diagnosed with Lynch syndrome and six patients harbored BRCA1 or BRCA2 mutations. One case underwent risk-reductive salpingo-oophorectomy as a BRCA1 mutant carrier was retrospectively diagnosed as occult cancer. Common TP53 mutations were detected in cancer and fallopian tube epithelial cells in the case.

    CONCLUSIONS:

    Here, we integrate family cancer history and histology in ovarian cancer cases as well as TP53 status in a BRCA1 mutant case into a discussion regarding carcinogenesis in a Japanese population. The TP53 status for the BRCA1 mutant case examined here supports the recently proposed theory that ovarian cancer develops because of BRCA1 or BRCA2 inactivation and/or TP53 mutations.

    There's another side to the Amy Robach breast cancer story



    healthnewsreview

      Health News Review

    Post ureteral stent removal symptoms




    urotubewide 

    urotoday 

    Tuesday, November 12, 2013

    Antegrade repositioning of Memokath stent in malignant ureteroileal anastomotic stricture (in an ovarian cancer patient)



    open access

    Case report 

    A 64-year-old lady was diagnosed to have locally advanced ovarian carcinoma 5 years prior to presentation. She had undergone debulking surgery with colostomy as well as ileal conduit diversion surgery. She had also undergone two courses of chemotherapy, and was also treated with fulguration that entailed tissue ablation using high-frequency electric sparks. Despite the aggressive treatment of the disease, she developed tumor recurrence that caused right hydronephrosis (and) and hydroureter. Endoscopic examination performed via the ileal conduit showed a 5-cm stricture of the ureteroileal junction caused by tumor infiltration. Balloon dilatation of the malignant stricture was performed, but there was still persistent contrast hold-up seen in the right collecting system. Subsequently, antegrade stenting of the malignant stricture was performed using a 6F double J stent. Unfortunately, there was recurrent distal migration of the double J stent into the conduit, requiring repeated repositioning of the stent under fluoroscopic guidance in the radiology department.....

    define: ureteroileal




     

    Circulating U2 Small Nuclear RNA Fragments as a Novel Diagnostic Tool for Patients with Epithelial Ovarian Cancer



    abstract

    Background: Ovarian cancer is the leading cause of death among malignancies in women. Despite advances in treatment, >50% of patients relapse. For disease monitoring, the identification of a blood-based biomarker would be of prime interest. In this regard, noncoding RNAs, such as microRNA (miRNA) or small nuclear RNA (snRNA), have been suggested as biomarkers for noninvasive cancer diagnosis. In the present study, we sought to identify differentially expressed miRNA/snRNA in sera of ovarian cancer patients and investigate their potential to aid in therapy monitoring.
    Methods: miRNA/snRNA abundance was investigated in serum (n = 10) by microarray analysis and validated in an extended serum set (n = 119) by reverse-transcription quantitative PCR.
    Results: Abundance of U2-1 snRNA fragments (RNU2-1f) was significantly increased in sera of ovarian cancer patients (P < 0.0001) and paralleled International Federation of Gynecology and Obstetrics stage as well as residual tumor burden after surgery (P < 0.0001 and P = 0.011, respectively). Moreover, for patients with suboptimal debulking, preoperative RNU2-1f concentration was associated with radiographic response after chemotherapy and with platinum resistance (P = 0.0088 and P = 0.0015, respectively). Interestingly, according to the RNU2-1f abundance dynamics, persistent RNU2-1f positivity before surgery and after chemotherapy identified a subgroup of patients with high risk of recurrence and poor prognosis.
    Conclusions: This is the first report to suggest that a circulating snRNA can serve as an auxiliary diagnostic tool for monitoring tumor dynamics in ovarian cancer. Our results provide a rationale to further investigate whether this high-risk patient group may benefit from additional therapies that are directly applied after chemotherapy.


     

    CDC - Gynecologic Cancers - Inside Knowledge Campaign



    Inside Knowledge Campaign  Inside Knowledge Campaign Logo

    Inside Knowledge Campaign

    The Inside Knowledge: Get the Facts About Gynecologic Cancer campaign raises awareness of the five main types of gynecologic cancer: cervical, ovarian, uterine, vaginal, and vulvar. It encourages women to pay attention to their bodies and know what is normal for them, so they can recognize the warning signs of gynecologic cancers and seek medical care. When gynecologic cancers are found early, treatment is most effective.

    Campaign Materials

    Inside Knowledge has created a suite of materials in English and Spanish for patients and health care providers. Fact sheets, a symptoms diary, Adobe PDF file [PDF-503KB] and posters on the five most common gynecologic cancers can be viewed, printed, and ordered online. Television and radio PSAs can be viewed and heard online; transcripts are available....
     

    Promoting Gynecologic Cancer Awareness at a Critical Juncture—Where Women and Providers Meet - Online First - Springer



    abstract

    $39.95 / €34.95 / £29.95*
    Given the absence of effective population-based screening tests for ovarian, uterine, vaginal, and vulvar cancers, early detection can depend on women and health care providers recognizing the potential significance of symptoms. In 2008, the Centers for Disease Control and Prevention’s (CDC) Inside Knowledge campaign began distributing consumer education materials promoting awareness of gynecologic cancer symptoms. We investigated providers’ in-office use of CDC gynecologic cancer materials and their recognition of the symptoms highlighted in the materials. We analyzed data from a national 2012 survey of US primary care physicians, nurse practitioners, and gynecologists (N = 1,380). Less than a quarter of providers (19.4 %) reported using CDC gynecologic cancer education materials in their offices. The provider characteristics associated with the use of CDC materials were not consistent across specialties. However, recognition of symptoms associated with gynecologic cancers was consistently higher among providers who reported using CDC materials. The possibility that providers were educated about gynecologic cancer symptoms through the dissemination of materials intended for their patients is intriguing and warrants further investigation. Distributing consumer education materials in health care provider offices remains a priority for the Inside Knowledge campaign, as the setting where women and health care providers interact is one of the most crucial venues to promote awareness of gynecologic cancer symptoms.

    An aspirin a day? Aspirin use across a spectrum of risk: cardiovascular disease, cancers and bleeds, Expert Opinion on Pharmacotherapy, Informa Healthcare



    Abstract

    "Aspirin or acetylsalicylic acid (ASA) is commonly used in the general population for primary prevention of cardiovascular disease (CVD). Strong evidence supports the use of ASA in secondary prevention of CVD; however, for primary prevention, potential benefits are offset by potential harms (primarily major bleeds), with no benefit in overall mortality. Anti-platelet agents, including ASA, are one of the most commonly implicated medications for hospital admissions related to adverse medication events. Studies of primary prevention in patients with risk factors for CVD also fail to show a benefit with ASA. Finally, evidence supporting ASA use for cancer prevention is limited. Health care providers should be aware of the benefits and risks associated with ASA use in primary and secondary prevention and discuss these with their patients in the context of individual patient values and preferences."


     

    Bridging Efforts to Longitudinally Improve and Evaluate VEnous thromboembolism prophylaxis uptake in hospitalized cancer patients through Interprofessional Teamwork



    abstract

    INTRODUCTION:

    Despite demonstrable risk of venous thromboembolism (VTE), thromboprophylaxis continues to be underutilized in hospitalized cancer patients. Our study evaluated institutional VTE prophylaxis rates after devising a series of strategic interventions to longitudinally improve adherence rates over a period of eight years.

    METHODS AND MATERIALS:

    Between 2004 and 2012, a series of interventions were implemented to improve the thromboprophylaxis rate among patients with solid tumours hospitalized at our institution using quality improvement methodology. Interventions included development of guidelines and institutional policies coupled with educational in-services for physicians, nurses and pharmacists and engagement of the Cancer Quality Committee. Thromboprophylaxis rates were monitored to assess response to interventions.

    RESULTS:

    At the outset in 2004, 11 of 57 (19.3%) eligible patients received appropriate pharmacological prophylaxis and formed the baseline of our analysis. Post-2009 policy implementation and educational sessions, 46.5% of an eligible 185 inpatients were administered thromboprophylaxis. Following a two-year grace period to allow for policy acceptance, three audits were conducted in 2011 for which an average prophylaxis rate of 62.3% resulted. In 2012, following another round of educational sessions, a 96.7% rate was achieved and maintained ten weeks later. Minimal bleeding risk was observed during this eight year initiative.

    CONCLUSION:

    A reproducible 96.7% prophylaxis uptake rate was the result of our perseverance and persistence in believing that culture change was inevitable through continuously collaborating with stakeholders at all levels.