Chemo drug (etoposide) in pregnancy may cause early menopause in daughters (mice study)

 (Etoposide) also known as: Trade names: Toposar^®, VePesid^®, Etopophos^® Other name: VP-16, Etoposide phosphate

medical news
  Saturday 13 August 2016 
 

"If the results we have seen in these mouse studies are replicated in human tissue, it could mean that girls born to moms who are taking etoposide during pregnancy have a reduced fertility window."

Prof. Norah Spears

The University of Edinburgh in the United Kingdom finds that etoposide - a chemotherapy drug used to treat lung cancer, ovarian cancer, leukemia, and lymphoma - may affect the future fertility of unborn baby girls.

Etoposide works by blocking an enzyme, which is necessary for cancer cells to divide and grow into two new cells. If this enzyme is blocked, the cell's DNA becomes tangled, and the cell can no longer divide.
According to Cancer Research UK, between 1-10 in every 100 people experience infertility due to the use of etoposide. Chemotherapy can stop the ovaries from producing eggs temporarily or sometimes permanently, and some people experience early menopause.

However, this research shows that etoposide damages the development of lab-grown mouse ovary tissue and affects specialized cells - called germ cells - that lead to egg production. Further studies are needed to observe if the same effect is true in human tissue.

Long-term effects of drug on reproductive system previously unknown

Experts caution that daughters of women who received chemotherapy during pregnancy should be informed that they might undergo early menopause.

 Around 1 in 1,000 pregnant women are diagnosed with cancer, requiring consideration for the use of chemotherapy during pregnancy. However, little is known about the possible long-term detrimental effects of etoposide on the reproductive system of the unborn child.

Racial/ethnic disparities in ovarian cancer treatment and survival

Abstract

Purpose: Among ovarian cancer patients, African American (AA) women experience poorer survival compared to other race/ethnicity groups. This has been attributed to differences in access to health care.
Experimental Design: We evaluated racial/ethnic differences in chemotherapy dosing and survival in a cohort study among members of Kaiser Permanente Northern California, and thus with equivalent access to health care. Analyses included epithelial invasive ovarian cancer cases (n=793) receiving adjuvant first-line therapy of carboplatin and paclitaxel with curative intent, with median follow-up of 50 months. Relative dose intensity (RDI) was computed for carboplatin and paclitaxel separately as dose administered/week divided by expected dose/week, and average RDI (ARDI) was then calculated for the regimen. Proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) after adjusting for relevant covariates.
Results: Compared to whites, AAs were more likely to have dose reduction (ARDI<85%), treatment delay, and early discontinuation. Hispanics were also more likely to have dose reduction, but less likely to have early discontinuation or treatment delay. After controlling for prognostic factors including ARDI, AA women had the worst survival. Compared to whites, adjusted HRs (95% CI) for overall mortality were 1.56  for AA; 0.89 for Asians; and 1.41 for Hispanics. Findings for ovarian cancer-specific mortality were similar.
Conclusions: Disparities in ovarian cancer treatment and survival in AA persisted among women with equal access to care. These findings warrant further evaluation of biological, personal, and social factors that may be responsible for these differences.

Perspective: Challenging Roadblocks to Cancer Cure (chronic vs cure...)

open access

The Pezcoller Symposium in Trento, Italy, June 2015, focused
entirely on the question of why advanced cancer cure is so
uncommon despite the extraordinarily rapid growth of invaluable
therapeutic information. Participants were asked to define and to
critically evaluate real and potential obstacles to permanent
disease eradication. High-level concepts on potential road blocks
to cures as well as opportunities for intervention in diverse areas of
investigation ranging from genomic alterations to metabolism,
microenvironment, immunity, and mechanotransduction were
discussed. Provocative concepts and novel therapeutic avenues
were proposed. What follows is a critical analysis of the highlights
of this meeting. Cancer Res; 76(17); 1–7. 2016 AACR.

 Introduction
Although cures or long-term, disease-free survival can be
achieved in certain cancers such as CML and testicular cancer,
others, particularly solid tumors, have eluded them altogether.On
the other hand, extended survival without definitive cure has been
achieved in many malignancies, either as a result of prevention or
chronic therapeutic approaches (e.g., prostate and breast cancer).
Therapies range from traditional chemotherapeutic agents to
targeted approaches with small molecules, to biological and,
most recently, powerful immunotherapeutic approaches.
Tumors also range in pathogenetic mechanisms, which, in turn,
may affect therapeutic responsiveness. Monogenic alterations,
such as certain genomic translocation-driving leukemias and
non–small cell lung cancers, are potentially treatable with targeted
agents. In contrast, most solid tumors with their complex genetic
alterations, their heterogeneity, clonal diversity, and intricate
microenvironments have proven to be a much more arduous
therapeutic problem.
Because of the difficulty in addressing cancers that are so diverse
and resourceful, some have advocated a goal of turning lethal
cancers into chronic diseases rather than curing them. Others
would argue that this is a defeatist approach that sets a "low bar"
and avoids decisive endpoints......

Validation of a second-generation multivariate index assay for malignancy risk of adnexal masses

open access (pdf)

Etoposide damages female germ cells in the developing ovary

open access

Background

Cancer is diagnosed in approximately one out of every 1000 pregnancies, often requiring consideration of chemotherapy administration to the pregnant woman [1, 2, 3, 4]. Chemotherapy administration during the first trimester is now largely avoided, as it is associated with increased risk of congenital malformations and high risk of spontaneous abortion [5]. However.....

Association of BRCA1 Mutations with Impaired Ovarian Reserve: Connection Between Infertility and Breast/Ovarian Cancer Risk

abstract

Medical University of South Carolina, Hollings Cancer Center, Charleston, South Carolina.

AbbVie, Pharmaceutical Research and Development, Chicago, Illinois.

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Department of Obstetrics and Gynecology-Clinical Genetics, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Purpose: Mutations in the BRCA1/2 genes are associated with breast and ovarian cancer susceptibility. Recent studies have suggested that the BRCA mutation might be associated with occult primary ovarian insufficiency. To evaluate fertility, several studies have validated anti-Mullerian hormone (AMH) as a direct biomarker for ovarian aging and it is considered a quantitative marker of ovarian reserve. We hypothesize that BRCA1 gene mutations will be negatively associated with AMH levels.

Methods: We evaluated 124 women aged 18–45 years participating in the Northwestern Ovarian Cancer Early Detection and Prevention Program. Patients with a history of cancer, ovarian surgery, or exposure to chemotherapy were excluded. Linear and logistic regression modeling were performed to evaluate the association between AMH levels, age, and BRCA1 mutation. In logistic models, the outcome ‘low AMH’ was defined as AMH <0.05 ng/mL. Logistic regression models were used to adjust for other factors, including body mass index (BMI), duration of birth control (BC), smoking, gravidity, and parity.
Results: Women with the BRCA1 mutation had a significant decline in AMH with age (p = 0.0011). BRCA1-positive women >35 years had 10 times the odds of a low AMH (<0.5 ng/mL) compared with women ≤35 years. With adjustment for BMI, duration of BC, smoking, gravidity, parity, and age >35, BRCA1 was still strongly associated with a low AMH (p = 0.037).

Conclusion: Women >35 with the BRCA1 mutation have a lower AMH, and hence ovarian reserve, than women without a BRCA mutation. Therefore, young adults with the BRCA1 mutation should be counseled regarding this potential decrease in ovarian reserve.

It’s not that confusing. Diet/exercise matter for cancer prevention (ref to NYTimes)

AICR Blog

Our Blog

Research news and views on preventing and surviving cancer

By Author AICRPosted on August 12, 2016
 
Not smoking will lower your risk of many cancers. Getting vaccinated will lower your risk of certain cancers. And eating a healthy diet along with exercising regularly will also lower your risk of certain cancers.
It’s not that confusing.
If you read a widely shared New York Times piece going around this week, you would think that you shouldn’t trust any evidence when it comes to diet and exercise and cancer risk. That’s not true.
It’s not a single study, or even several.......

Identification and Functional Testing of ERCC2 Mutations in a Multi-national Cohort of Pts (Familial Breast/Ovarian)

open access: 
PLOS Genetics: Identification and Functional Testing of ERCC2 Mutations in a Multi-national Cohort of Patients with Familial Breast- and Ovarian Cancer

The increasing application of gene panels for familial cancer susceptibility disorders will probably lead to an increased proposal of susceptibility gene candidates. Using ERCC2 DNA repair gene as an example, we show that proof of a possible role in cancer susceptibility requires a detailed dissection and characterization of the underlying mutations for genes with diverse cellular functions (in this case mainly DNA repair and basic cellular transcription). In case of ERCC2, panel sequencing of 1345 index cases from 587 German, 405 Lithuanian and 353 Czech families with breast and ovarian cancer (BC/OC) predisposition revealed 25 mutations (3 frameshift, 2 splice-affecting, 20 missense), all absent or very rare in the ExAC database. While 16 mutations were unique, 9 mutations showed up repeatedly with population-specific appearance.....

Terence Corcoran: Ontario’s minister of monopoly (healthcare) opinion: patients last

National Post

...Should Ontario’s 42,200 OMA members (including 3,000 medical students) say no to the agreement, it would send the province’s bureaucratic central planners back to the drawing board. If they accept the compensation agreement, the OMA will have helped advance the Wynne government’s imposition of its massive interventionist Patients First command-and-control health-care system.

The hallmarks of central planning are maldistribution of resources, inadequate supply, shortages, waiting lists, lineups, price controls and breakdowns. If the economic history of command and control teaches anything, it is that you can’t put patients first by putting the suppliers of patient care last. 

National Post
tcorcoran@nationalpost.com
Twitter.com/TerenceCorcoran

recent (sundry) items: google scholar search "ovarian cancer"

http://feeds.feedburner.com/blogspot/UnpPW
 

Scholar Alert: [ intitle:"ovarian cancer" ]; Articles excluding patents

Socioeconomic Status in Relation to the Risk of Ovarian Cancer in African-American Women: A Population-Based Case-Control Study

AJ Alberg, PG Moorman, S Crankshaw, F Wang… - American Journal of …, 2016

Abstract We investigated the association between socioeconomic status and ovarian cancer
in African-American women. We used a population-based case-control study design that
included case patients with incident ovarian cancer (n= 513) and age-and area-matched ...

Clinical relevance of kallikrein-related peptidase 6 (KLK6) and 8 (KLK8) mRNA expression in advanced serous ovarian cancer.

N Ahmed, J Dorn, R Napieralski, E Drecoll, M Kotzsch… - Biological chemistry, 2016

Most members of the kallikrein-related peptidase family have been demonstrated to be
dysregulated in ovarian cancer and modulate tumor growth, migration, invasion, and
resistance to chemotherapy. In the present study, we assessed the mRNA expression ...

European Society of Gynaecologic Oncology Quality Indicators for Advanced Ovarian Cancer Surgery.

D Querleu, F Planchamp, L Chiva, C Fotopoulou… - International Journal of …, 2016

Objectives: The surgical management of advanced ovarian cancer involves complex
surgery. Implementation of a quality management program has a major impact on survival.
The goal of this work was to develop a list of quality indicators (QIs) for advanced ovarian ...

CXCL9 and CXCL10 predict survival and are regulated by cyclooxygenase inhibition in advanced serous ovarian cancer

H Bronger, J Singer, C Windmüller, U Reuning, D Zech… - British Journal of Cancer, 2016

Background: Tumour-infiltrating lymphocytes (TILs) are associated with improved survival in
several epithelial cancers. The two chemokines CXCL9 and CXCL10 facilitate chemotactic
recruitment of TILs, and their intratumoral accumulation is a conceivable way to improve ...

[PDF] Association of Immunosuppression with DR6 Expression during the Development and Progression of Spontaneous Ovarian Cancer in Laying Hen Model

SR McNeal, P Bitterman, JM Bahr, SL Edassery… - Journal of Immunology …, 2016

Ovarian cancer (OVCA) mainly disseminates in the peritoneal cavity. Immune functions are
important to prevent OVCA progression and recurrence. The mechanism of
immunosuppression, a hallmark of tumor progression, is not well understood. The goal of ...

Hypoxia-NOTCH1-SOX2 signaling is important for maintaining cancer stem cells in ovarian cancer.

EJ Seo, DK Kim, IH Jang, EJ Choi, SH Shin, SI Lee… - Oncotarget, 2016

Hypoxia and NOTCH signaling have been reported to be associated with the self-renewal
and drug resistance of cancer stem cells (CSCs). However, the molecular mechanisms by
which hypoxia and NOTCH signaling stimulate the self-renewal and drug resistance of ...

The status of poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors in ovarian cancer, part 1: olaparib.

RE Miller, JA Ledermann - Clinical advances in hematology & oncology: H&O, 2016

Poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors have shown promising
clinical activity in epithelial ovarian cancer. Following the observation in vitro that PARP
inhibition is synthetically lethal in tumors with BRCA mutations, PARP inhibition has ...

Depletion of Dicer promotes epithelial ovarian cancer progression by elevating PDIA3 expression

Y Zhu, L Cai, J Guo, N Chen, X Yi, Y Zhao, J Cai… - Tumor Biology, 2016

Abstract Dicer is an essential component of the microRNA (miRNA) processing machinery
whose low expression is associated with advanced stage and poor clinical outcome in
epithelial ovarian cancer. To investigate the functional relevance of Dicer in epithelial ...

Use of PlasmaJet for Peritoneal Carcinomatosis in Ovarian Cancer.

E Panuccio, K Leunen, E Van Nieuwenhuysen… - International journal of …, 2016

OBJECTIVE: This study aimed to assess the role and complications of extensive
cytoreduction with PlasmaJet (Plasma Surgical, Roswell, Ga) in ovarian cancer with
peritoneal carcinomatosis. MATERIALS: All patients undergoing primary, secondary, or ...

Exendin-4 inhibits growth and augments apoptosis of ovarian cancer cells

W He, S Yu, L Wang, M He, X Cao, Y Li, H Xiao - Molecular and Cellular …, 2016

Abstract Glucagon-like peptide (GLP)-1 promotes proliferation and survival in β-cell;
however, whether GLP-1 receptor agonists promote growth of human ovarian cancer cells
remain unknown. We aimed to explore the effects of GLP-1 agents on ovarian cancer cells ...

Therapeutic targets and new directions for antibodies developed for ovarian cancer

HJ Bax, DH Josephs, G Pellizzari, JF Spicer, A Montes… - mAbs, 2016

Abstract Antibody therapeutics against different target antigens are widely used in the
treatment of different malignancies including ovarian carcinomas, but this disease still
requires more effective agents. Improved understanding of the biological features, ...

Current South African clinical Practice in Debulking Surgery for Ovarian Cancer.

J Billson, FH van der Merwe, RP Soeters - … of gynecological cancer: official journal of …, 2016

INTRODUCTION: The aim of this study was to assess practice patterns and rationale with
regard to debulking surgery for advanced epithelial ovarian carcinoma among South African
Gynaecological oncologists. METHODS: A survey was distributed to all practicing ...

The Emerging Role of Tyrosine Kinase Inhibitors in Ovarian Cancer Treatment: A Systematic Review

I Ntanasis-Stathopoulos, G Fotopoulos, IG Tzanninis… - Cancer Investigation, 2016

ABSTRACT The present systematic review summarizes current evidence regarding the
mechanisms of action, the efficacy, and the adverse effects of tyrosine kinase inhibitors
(TKIs) in ovarian cancer patients. Phase II and III clinical trials were sought in the PubMed ...

Bayesian analysis for mixture nonlinear mixed-effects models with skewed random effects and errors with application to an ovarian cancer study

CC Chen - 2016

Abstract It is common to analyze longitudinal data using nonlinear mixed-effects (NLME)
model. And we often use NLME model with normality and homogeneity assumption.
However, this assumption may be unrealistic in practice. Our aim is to model the longitu-

[HTML] Locomotor proteins in tissues of primary tumors and metastases of ovarian and breast cancer

IV Kondakova, NV Yunusova, LV Spirina, EE Shashova… - PHYSICS OF CANCER: …, 2016

... and metastases of ovarian and breast cancer. Contents of p45 Ser β-catenin and
the actin severing protein gelsolin were decreased in metastases of ovarian cancer
relative to primary tumors. The level of the cofilin, functionally ...

[PDF] Investigating the Role of Extracellular Matrix Proteins in Ovarian Folliculogenesis and Ovarian Cancer

A Carrier - 2016

Abstract The extracellular matrix (ECM) is a highly organized, dynamic structure that
maintains tissue integrity and regulates biological processes involved in organ development
and function. To explore the role of ECM proteins in ovarian physiology and pathology, my ...

[PDF] Transcription in Ovarian Cancer Cell Lines

HW von König, M Breidenbach, MM Valter…

Abstract The clinical observation of the multidrug resistance (MDR) phenotype is often
associated with overexpression of the mdr1 gene, in particular with respect to ovarian
cancer. However, until now the mdrl-inducing potential of commonly used antineoplastics ...

Prevalence and distribution pattern of nodal metastases in advanced ovarian cancer

C Bachmann, R Bachmann, B Kraemer, SY Brucker… - Molecular and Clinical Oncology

Abstract The objective of this study was to examine the relevance of pelvic and para‑aortic
lymph node involvement and the tumour characteristics affecting nodal metastases and
survival in primary advanced ovarian cancer. A total of 130 consecutive patients were ...

[PDF] Microfluidics and spectroscopic imaging for personalized medicine in ovarian cancer

AM Mes-Masson, T Gervais

With certain cancers, such as ovarian cancers, a significant number of patients are non-
responsive to the standard chemotherapy treatment. These patients, therefore, experience
the negative side effects of chemotherapy without clinical benefits. With the everincreasing ...

Characterization of BRCA1 and BRCA2 variants found in a Norwegian breast or ovarian cancer cohort

E Jarhelle, HMFR Stensland, L Mæhle, M Van Ghelue - Familial Cancer

Abstract Germline mutations in BRCA1 and BRCA2 cause hereditary breast and ovarian
cancer. Molecular screening of these two genes in patients with a family history of breast or
ovarian cancer has revealed pathogenic variants as well as genetic variants of unknown ...

---

Patients on Social Media Cause Ethics Headache for Doctors

Medscape (Reuters Health)

How can we encourage cancer patients to share their health data? (Markman)

article

Stanford, Google Partner on Genomic Health Analysis

business news

correspondence: Patient Power: looking for ovarian cancer participation (advisory board)

 Patient Power website (main page)

 August 9, 2016

Good afternoon. My name is Theresa Clementi from Patient Power. I am  
contacting you because I found your blog about ovarian cancer through Help  Keep A Sister Alive. 

Our team at Patient Power is very committed to helping  
drug developers develop better treatments for patients. While part of that  
is helping people understand and being aware of clinical trials, another  
part is connecting patients with the people that develop new therapies so  
they know what's important, challenges patients face, and importance of  
hearing a first hand perspective of facing ovarian cancer. Right now we are  
looking for several ovarian cancer patients and care partners to  
participate on an advisory board to give their personal feedback. If you  
are willing or know anyone willing to tell their story to the people who  
make medicines like these, let us know. You can email my colleague Autumn,  
at autumn@patientpower.info
 
Thank you!, Theresa
 
Regards,
Theresa Clementi | theresa@patientpower.info

Population-based precision cancer screening: a symposium on evidence, epidemiology, and next steps

abstract

 Precision medicine, an emerging approach for disease treatment that takes into account individual variability in genes, environment, and lifestyle, is under consideration for preventive interventions, including cancer screening. On September 29, 2015, the National Cancer Institute sponsored a symposium entitled "Precision Cancer Screening in the General Population: Evidence, Epidemiology, and Next Steps". The goal was two-fold: to share current information on the evidence, practices, and challenges surrounding precision screening for breast, cervical, colorectal, lung, and prostate cancers, and to allow for in-depth discussion among experts in relevant fields regarding how epidemiology and other population sciences can be used to generate evidence to inform precision screening strategies. Attendees concluded that the strength of evidence for efficacy and effectiveness of precision strategies varies by cancer site, that no one research strategy or methodology would be able or appropriate to address the many knowledge gaps in precision screening, and that issues surrounding implementation must be researched as well. Additional discussion needs to occur to identify the high priority research areas in precision cancer screening for pertinent organs and to gather the necessary evidence to determine whether further implementation of precision cancer screening strategies in the general population would be feasible and beneficial.

Refining Ovarian Cancer Test accuracy Scores (ROCkeTS): protocol for a prospective longitudinal test accuracy study to validate new risk scores in women with symptoms of suspected ovarian cancer

open access:
Refining Ovarian Cancer Test accuracy Scores (ROCkeTS): protocol for a prospective longitudinal test accuracy study to validate new risk scores in women with symptoms of suspected ovarian cancer
  

 The study will recruit 2450 patients from 15 UK sites.

Methods and analysis ROCkeTS comprises four parallel phases. The full ROCkeTS protocol can be found at http://www.birmingham.ac.uk/ROCKETS. Phase III is a prospective test accuracy study.

ROCkeTS study design

Aim of the study

• To derive and validate risk prediction models that estimate the probability of having OC for women with symptoms suggestive of OC for postmenopausal and premenopausal women.
• To identify optimal risk thresholds of best models for the diagnosis of OC that can guide patient management.
  
  

  Design

  The ROCkeTS study is a single-arm prospective cohort diagnostic test accuracy study to evaluate existing and novel risk prediction models for premenopausal and postmenopausal women with symptoms.
  
  

A BRCA1/2 mutational signature and survival in ovarian high grade serous carcinoma

Abstract

Background: Mutational signatures have been identified by the broad sequencing of cancer genomes and reflect underlying processes of mutagenesis. The clinical application of mutational signatures is not well defined. Here we aim to assess the prognostic utility of mutational signatures in ovarian high grade serous carcinoma.
Methods: Open access data of 15,439 somatic mutations of 310 ovarian high grade serous carcinomas from The Cancer Genome Atlas (TCGA) are used to construct a Bayesian model to classify each cancer as either having or lacking a BRCA1/2 mutational signature. We evaluate the association of the BRCA1/2 signature with overall survival on the TCGA dataset and on an independent cohort of 92 ovarian high grade serous carcinomas from the Australian Ovarian Cancer Study (AOCS).
Results: Patients from TCGA with tumors harboring the BRCA1/2 mutational signature have improved survival (55.2 months vs. 38.0 months), which is independent of BRCA1/2 gene mutation status, age, stage and grade (HR = 0.64, p = 0.02). In the AOCS dataset, the BRCA1/2 mutational signature is also associated with improved overall survival (46.3 months vs. 23.6 months) independent of age and stage (HR = 0.52, p = 0.007).
Conclusions: A BRCA1/2 mutational signature is a prognostic marker in ovarian high grade serous carcinoma. Mutational signature analysis of ovarian cancer genomes may be useful in addition to testing for BRCA1/2 mutations.
Impact: This study identifies the use of mutational signatures as a biomarker for survival outcome in ovarian high grade serous carcinoma. 

Ovarian cancer in the older woman - Journal of Geriatric Oncology

abstract

Ovarian cancer is the seventh most common cancer in women worldwide and accounts for nearly 4% of all new cases of cancer in women. Almost half of all patients with ovarian cancer are over the age of 65 at diagnosis, and over 70% of deaths from ovarian cancer occur in this same age group. As the population ages, the number of older women with ovarian cancer is increasing. Compared to younger women, older women with ovarian cancer receive less surgery and chemotherapy, develop worse toxicity, and have poorer outcomes. They are also significantly under-represented in clinical trials and thus application of standard treatment regimens can be challenging. Performance status alone has been shown to be an inadequate tool to predict toxicity of older patients from chemotherapy. Use of formal geriatric assessment tools is a promising direction for stratifying older patients on trials. Elderly-specific trials, adjustments to the eligibility criteria, modified treatment regimens, and interventions to decrease morbidities in the vulnerable older population should be encouraged.

Somatic mutation profiles in primary colorectal cancers and matching ovarian metastases: Identification of driver and passenger mutations

open access:
Somatic mutation profiles in primary colorectal cancers and matching ovarian metastases: Identification of driver and passenger mutations

• Abstract
• Introduction
• Materials and methods
• Results
• Discussion and Conclusion
• Acknowledgements
• Author contributions

• ---

• Supporting Information
• References
• Related Content

 However, in up to 38% of cases, ovarian metastasis detection may precede the detection of the primary CRC [9–11]. In such cases, it is important for treatment
strategies to recognize that the ovarian tumour is a metastasis and not a primary ovarian tumour. Extensive genomic profiling of CRCs and primary ovarian tumours has revealed a limited number of genes helpful in discriminating between these malignancies [12].

 CRCs metastasizing to the ovaries did not show a
specific mutation profile in comparison to consecutive
series of CRC, nor did the ovarian metastases.

open access: FERTILITY-SPARING SURGERY IN EPITHELIAL OVARIAN CANCER: A SYSTEMATIC REVIEW OF ONCOLOGICAL ISSUES

pdf
 August 8, 2016

 Conservative treatment to preserve fertility in ovarian cancer can be safely performed for stage IA and IC grade 1 and 2 disease and stage IC1 according to the new FIGO staging system. For patients with "less favourable" prognostic factors (grade 3, stage IC3 disease, clear cell tumour), the safety of FSS could not be confirmed but patients should be informed that radical treatment probably may not necessarily improve their oncological outcome. FSS should remain contraindicated for stage II/III disease (whatever the histologic subtype).

 Introduction
 
Fertility-sparing surgery (FSS) of epithelial ovarian cancer (EOC) is based on unilateral (salpingo-)oophorectomy and complete surgical staging. This empirical treatment option had initially been proposed to young women presenting with an early-stage invasive tumour and a low risk of recurrence [1]. The first large series specifically devoted to this management was published nearly 5 decades ago (mixing different subtypes of ovarian tumours)[2]. Different publications, initially mixing different subtypes (EOC and borderline tumours and/or epithelial and non-epithelial cancers) and more recently specifically dedicated to EOC, have been reported [3-6]. Five years ago, international recommendations were finalized concerning the indications and modalities for FSS in EOC [7].

Nevertheless, many questions continue to fuel debate and remain unclear concerning this management. These questions concern oncological outcomes and fertility issues. The fertility issues will not be covered in the present review most debatable and strategic (and finally philosophical) questions concern the oncological issues......

JCO open access: Neoadjuvant Chemotherapy for Newly Diagnosed, Advanced Ovarian Cancer

open access:
August 8, 2016
Neoadjuvant Chemotherapy for Newly Diagnosed, Advanced Ovarian Cancer: Society of Gynecologic Oncology and American Society of Clinical Oncology Clinical Practice Guideline

Navigate This Article

1. Top
2. Abstract
3. INTRODUCTION
4. GUIDELINE QUESTIONS
5. METHODS
6. RESULTS
7. RECOMMENDATIONS
8. PATIENT AND CLINICIAN COMMUNICATION
9. HEALTH DISPARITIES
10. MULTIPLE CHRONIC CONDITIONS
11. COST IMPLICATIONS
12. EXTERNAL REVIEW
13. GUIDELINE IMPLEMENTATION
14. FUTURE DIRECTIONS
15. AUTHOR CONTRIBUTIONS
16. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
17. Acknowledgment
18. Appendix
19. Footnotes
20. REFERENCES

 Recommendations All women with suspected stage IIIC or IV invasive epithelial ovarian cancer should be evaluated by a gynecologic oncologist prior to initiation of therapy. The primary clinical evaluation should include a CT of the abdomen and pelvis, and chest imaging (CT preferred). Women with a high perioperative risk profile or a low likelihood of achieving cytoreduction to < 1 cm of residual disease (ideally to no visible disease) should receive neoadjuvant chemotherapy. Women who are fit for primary cytoreductive surgery, and with potentially resectable disease, may receive either neoadjuvant chemotherapy or primary cytoreductive surgery. However, primary cytoreductive surgery is preferred if there is a high likelihood of achieving cytoreduction to < 1 cm (ideally to no visible disease) with acceptable morbidity. Before neoadjuvant chemotherapy is delivered, all patients should have confirmation of an invasive ovarian, fallopian tube, or peritoneal cancer. Additional information is available at www.asco.org/NACT-ovarian-guideline and www.asco.org/guidelineswiki.

Neoadjuvant Chemo for Ovarian Ca Highlighted in New Guidelines (ASCO/SGO)

medscape

 Neoadjuvant chemotherapy is the preferred treatment option for women with advanced ovarian and related cancers if it is unlikely that primary cytoreductive surgery (PCS) can reduce disease to less than 1 cm. It is also an alternative to surgery for women with potentially resectable disease who prefer the neoadjuvant approach, as chemotherapy is not inferior to surgery in terms of progression-free or overall survival, new guidelines indicate.
The new guidelines were issued jointly by the American Society of Clinical Oncology and the Society of Gynecologic Oncology and were published online August 8 in the Journal of Clinical Oncology and Gynecologic Oncology.
"For a long time, physicians assumed that doing immediate surgery when a woman was diagnosed with ovarian cancer was the best possible treatment," lead author Alexi Wright, MD, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, told Medscape Medical News.....

(2) Delirium in cancer patients presenting to emergency department

1. 1. Discipline (abstract)

      Symptom Control and Palliative Care

      Delirium frequency among advanced cancer patients presenting to an emergency department: A prospective, randomized, observational studyAhmed F. Elsayem, Eduardo Bruera, Alan D. Valentine, Carla L. Warneke, Sai-Ching J. Yeung, Valda D. Page, Geri L. Wood, Julio Silvestre, Holly M. Holmes, Patricia A. Brock and Knox H. Todd
      Version of Record online: 25 JUL 2016 | DOI: 10.1002/cncr.30133
      

      • 

      
      

      With a frequency of at least 9% according to the Confusion Assessment Method, delirium is relatively frequent among advanced cancer patients visiting the emergency department of The University of Texas MD Anderson Cancer Center, and all of these patients are also delirious according to the Memorial Delirium Assessment Scale. Delirium is frequently missed by emergency department physicians (41% of cases) despite prior education; this highlights the need for systematic screening for delirium among advanced cancer patients visiting the emergency department. See also pages 000-000.

      • Abstract
      • Article
      • PDF(173K)
      • References
      • Request Permissions

2. Editorial

   1. Cancer patients with delirium in the emergency department: A frequent and distressing problem that calls for better assessmentPeter G. Lawlor
      Version of Record online: 25 JUL 2016 | DOI: 10.1002/cncr.30132
      

      Delirium is acknowledged as a common complication of cancer that frequently results in a visit to the emergency department, yet it is often poorly assessed, and the diagnosis is missed as a result. Because age is a major risk factor for delirium and population demographics are changing, there is a critical need to develop optimal delirium screening strategies for cancer patients who access this point of care. See also pages 000-000.

      • Abstract
      • Article
      • PDF(78K)
      • References
      • Request Permissions

Implication of genomic characterization in synchronous endometrial and ovarian cancers of endometrioid histology

Implication of genomic characterization in synchronous endometrial and ovarian cancers of endometrioid histology
 

Objectives

Synchronous endometrial and ovarian carcinomas (SEOCs) present gynecologic oncologists with a challenging diagnostic puzzle: discriminating between double primary cancers and single primary cancer with metastasis. We aimed to determine the clonal relationship between simultaneously diagnosed endometrial and ovarian carcinomas.

Methods (Taiwan)

Fourteen pairs of SEOCs of endometrioid type and two pairs of SEOCs with disparate histologic types (control for dual primary tumors) were subjected to massively parallel sequencing (MPS) and molecular inversion probe microarrays.

Results

Thirteen of the 14 pairs of SEOCs harbored somatic mutations shared by both uterine and ovarian lesions, indicative of clonality. High degree of chromosomal instability in the tumors from 10 patients who received adjuvant chemotherapy, of whom 9 had synchronous carcinomas with significantly overlapping copy number alterations (CNAs), suggestive of single primary tumors with metastasis. The clonal relationship determined by genomic analyses did not agree with clinicopathological criteria in 11 of 14 cases. Minimal CNAs were identified in both ovarian and endometrial carcinomas in 4 patients, who did not receive adjuvant chemotherapy and experienced no recurrent diseases. In contrast, two of the 10 patients with chromosomally unstable cancers developed recurrent tumors.

Conclusion

Our findings support a recent paradigm-shifting concept that most SEOCs (Synchronous endometrial and ovarian carcinomas) originate from a single tumor. It also casts doubt on the clinicopathological criteria used to distinguish between dual primary tumors and single primary tumor with metastasis. Testing of CNAs on SEOCs may help determining the need of adjuvant therapy.

Early warning score: An indicator of adverse outcomes in postoperative patients on a gyn oncology service

abstract:
Early warning score: An indicator of adverse outcomes in postoperative patients on a gynecologic oncology service
 

Objective

In 2014, our hospital implemented an early warning score (EWS) to identify inpatients at risk for clinical deterioration. EWS ≥ 8 is associated with ≥10% mortality in medical admissions. Since postoperative hemodynamic changes may alter EWS, we evaluated EWS in post-laparotomy patients.

Methods

Gynecologic oncology patients admitted for laparotomy from 9/1/2014 to 7/31/2015 were categorized by highest EWS during admission: <5, 5–7, and ≥8.

The primary outcome was a composite including death, ICU transfer, rapid response team activation, pulmonary embolus, sepsis, and reoperation. For patients with the composite, highest EWS prior to that outcome was evaluated. Secondary outcomes were length of stay (LOS), readmission, and transfusion. Groups were compared using chi-square test for trend....

Results

411 patients were included: 217 (52.8%) with EWS < 5, 151 (36.7%) with EWS 5–7, and 43 (10.5%) with EWS ≥ 8. The composite occurred in 32.6% of patients with EWS ≥ 8, 7.3% with EWS 5–7, and 0% with EWS < 5 (p < 0.01). EWS ≥ 8 was associated with longer LOS, higher readmission rate, and more transfusions. For the composite, the area under the ROC curve was 0.89 (95% CI 0.84–0.94). EWS ≥ 5 had 100% sensitivity and 56.2% specificity for the primary outcome; EWS ≥ 8 had 56.0% sensitivity and 92.5% specificity for the primary outcome.

Conclusions

EWS  ≥ 5 after laparotomy is associated with adverse outcomes. Future studies should evaluate the ability of EWS to predict and prevent these outcomes.

When Do Late Effects in Childhood Cancer Survivors Cease Emerging? The Endocrine Answer

open access

Monitoring and screening should accord with the COG guidelines and are optimally carried out in a dedicated survivorship clinic focused on adult survivors of childhood cancer and intimately associated with endocrinologists familiar with the issues of this adult population, which are fundamentally different from the issues faced by survivors of adult or even adolescent and young adult cancers. Screening should not be considered complete based on a single testing episode.....

Primary pure spindle cell carcinoma (sarcomatoid carcinoma) of the ovary

Primary pure spindle cell carcinoma (sarcomatoid carcinoma) of the ovary: A case report with immunohistochemical study | Diagnostic Pathology | Full Text
 

Case presentation

This case report refers to a sarcomatoid carcinoma of the ovary in in a 57 year-old woman with abdominal pain.

 Ovarian carcinosarcomas, also known as malignant mixed mesodermal tumors or malignant mixed Müllerian tumors, are exceedingly rare, and comprise only 1-3 % of ovarian malignancies [14, 15].

Conclusion

Primary ovarian spindle cell carcinoma is a rare neoplasm, which must be considered in the differential diagnosis of solid ovarian mass with spindle cell appearance. This case adds to our knowledge of the biological behavior of these rare neoplasms. The distinction from true sarcomas and carcinosarcomas is important because of the more favorable prognosis of the spindle cell carcinomas. However their diagnosis necessitates a careful tissue sampling and immunohistochemical staining.

(Valley Fever) Coccidioidomycosis in Patients with Selected Solid Organ Cancers: A Case Series/Review

abstract:
Coccidioidomycosis in Patients with Selected Solid Organ Cancers: A Case Series and Review of Medical Literature

 Coccidioidomycosis is a common infection in the desert southwestern USA; approximately 3 % of healthy persons in Arizona alone become infected annually. Coccidioidomycosis may be severe in immunocompromised persons, but experience among patients with solid organ cancer has not been fully described. Therefore, we aimed to describe the clinical courses of patients whose cancers were complicated by coccidioidomycosis at our institution, which is located in an area with endemic Coccidioides. To do so, we conducted a retrospective review from January 1, 2000, through December 31, 2014, of all patients with breast, colorectal, or ovarian cancer whose cancer courses were complicated by coccidioidomycosis. We identified 17,576 cancer patients; 14 (0.08 %) of these patients met criteria for proven or probable coccidioidomycosis diagnosed within the first 2 years after the cancer diagnosis. All of these patients had primary pulmonary coccidioidomycosis, none had relapsed prior infection, and 1 had possible extrapulmonary dissemination. Five had active coccidioidal infection during chemotherapy, 1 of whom was hospitalized for coccidioidal pneumonia. All were treated with fluconazole, and all improved clinically. Eleven did not require prolonged courses of fluconazole. There were no clearly demonstrated episodes of relapsed infection. In conclusion, coccidioidomycosis was not a common complication of breast, colorectal, or ovarian cancers in patients treated at our institution, and it was not commonly complicated by severe or disseminated infection.

Ovarian Carcinoma With Isolated Spinal Cord Metastasis (case report/review)

 

Open access

Ovarian cancer metastasis to the spinal cord is quite rare, and few case reports have been published previously. Herein, we present a case of a patient who was treated for ovarian cancer and was thought to be disease free for 17 months, then presented with lower limb weakness. She was found to have a T11-T12 metastatic intramedullary spinal cord lesion. On pathology, the diagnosis of metastatic ovarian adenocarcinoma was made. This report highlights the importance of maintaining a low threshold for ovarian cancer metastases to the spinal cord when patients present with neurologic sequelae, even in the setting of normal laboratory values, as early detection can prevent permanent neurological consequences.

Discussion

Intramedullary spinal cord metastasis is quite rare, with a reported prevalence of up to 2.1% in an autopsy series of patients with cancer.³ Patients most commonly present with sensory deficits (40% to 90%) and pain (83% to 95%), with weakness (60% to 85%) and autonomic dysfunction (40% to 57%) being less common.²

The mechanism of metastatic spread for ovarian cancer may explain this phenomenon. Ovarian cancer does not exhibit the classic hematogenous spread found in most other cancers. Studies suggest that serous ovarian carcinomas grow very efficiently within the peritoneal cavity, but rarely metastasize outside of the area. When metastasis does occur, the hypothesized process states that as tumor cells detach singularly or in clusters from the primary tumor, they then travel by peritoneal fluid into the peritoneum and omentum.⁴

Distant metastases have been reported to the liver, brain, and other sites. Clinical predictors for distant metastasis remain unclear. Possible correlations are P53 mutations, genomic instability, and vascularization of the tumor. One of the few studies regarding distant metastasis in ovarian cancer studied 130 patients with ovarian cancer. Twenty-two percent were found to have distant metastasis either on initial presentation or during the course of the treatment. Multiple variables were considered as possible predictors of distant metastasis, including p53 null mutation; high-stage, high-grade, nodal metastasis; and presence of ascites. P53 null mutation was the most significant of these, followed by stage.^5....

  It is likely because the rarity of this condition may have contributed to the initial referral for physical therapy rather than establishing workup and proceeding with imaging studies. On her current presentation, the normal CA 125 level was misleading as well, and likely lead to increased time spent on exclusion of other diagnoses and performance of unnecessary tests such as lumbar puncture. Other published cases also reported normal Ca 125 levels, and no diagnostic value of lumbar puncture.¹

Specialized attention to patients with history of ovarian cancer and neurologic sequelae, including a detailed neurological exam or spinal MRI, may be employed in the future as screening measures for the benefit of patients with this uncommon condition.

Free Podcast (17:42 min) How much do we know about the clinical trials behind drugs approved by the FDA?

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EPISODE DESCRIPTION

On Biotech Nation with Dr Moira Gunn, how much do we know about the clinical trials behind drugs approved by the FDA? JENNIFER MILLER, the Founder and President of Bioethics, International and a professor at NYU Medical School, talks about the Good Pharma Scorecard.

Discussing Sexuality With Women Considering Risk-Reducing Sa... : International Journal of Gynecological Cancer

abstract 
Discussing Sexuality With Women Considering Risk-Reducing Salpingo-oophorectomy: An International Survey of Current Practice in Gynecologic Oncology

Objective: To determine how frequently gynecologic oncologists discuss sexuality with women considering risk-reducing salpingo-oophorectomy. Secondary objectives were to assess the availability of resources, and the barriers to discussing sexuality.

Methods: Members of the Australian Society of Gynaecologic Oncologists, International Gynecologic Cancer Society, and Society of Gynecologic Oncology were invited to complete an online survey. Questions addressed frequency of, and barriers to, discussing sexuality, and availability of resources related to sexual issues.

Results: Three hundred eighty-eight physicians in 43 countries responded from 4,006 email invitations (9.7%). Ninety-one percent reported discussing sexuality preoperatively, and 61% discuss it with every patient. Factors associated with higher rates of discussion were female sex, higher level of training, time in practice, and consulting more risk-reducing salpingo-oophorectomy patients per month. Commonly discussed issues were vasomotor menopausal symptoms (91%) and vaginal dryness (85%). Eighty-eight percent of respondents believed that sexuality should be discussed preoperatively, and most felt that it is their responsibility (82%). Fear of causing distress was the most common barrier to discussing sexuality (49%). Twenty-four percent felt that they did not have adequate training to discuss sexual function.

Conclusions: Although most respondents believed that discussing sexuality should occur preoperatively, only 61% discuss this with every patient. Resources specifically relating to sexuality are limited. The most common barrier to discussing sexuality was fear of causing distress. Nearly one quarter of gynecologic oncologists felt inadequately trained to discuss sexual function.

European Society of Gynaecologic Oncology Quality Indicators for Advanced Ovarian Cancer Surgery

abstract:
European Society of Gynaecologic Oncology Quality Indicators... : International Journal of Gynecological Cancer

Objectives: The surgical management of advanced ovarian cancer involves complex surgery. Implementation of a quality management program has a major impact on survival. The goal of this work was to develop a list of quality indicators (QIs) for advanced ovarian cancer surgery that can be used to audit and improve the clinical practice. This task has been carried out under the auspices of the European Society of Gynaecologic Oncology (ESGO).

Methods: Quality indicators were based on scientific evidence and/or expert consensus. A 4-step evaluation process included a systematic literature search for the identification of potential QIs and the documentation of scientific evidence, physical meetings of an ad hoc multidisciplinarity International Development Group, an internal validation of the targets and scoring system, and an external review process involving physicians and patients.

Results: Ten structural, process, or outcome indicators were selected. Quality indicators 1 to 3 are related to achievement of complete cytoreduction, caseload in the center, training, and experience of the surgeon. Quality indicators 4 to 6 are related to the overall management, including active participation to clinical research, decision-making process within a structured multidisciplinary team, and preoperative workup. Quality indicator 7 addresses the high value of adequate perioperative management. Quality indicators 8 to 10 highlight the need of recording pertinent information relevant to improvement of quality. An ESGO-approved template for the operative report has been designed. Quality indicators were described using a structured format specifying what the indicator is measuring, measurability specifications, and targets. Each QI was associated with a score, and an assessment form was built.

Conclusions: The ESGO quality criteria can be used for self-assessment, for institutional or governmental quality assurance programs, and for the certification of centers. Quality indicators and corresponding targets give practitioners and health administrators a quantitative basis for improving care and organizational processes in the surgical management of advanced ovarian cancer.

A Phase I Study of Unimolecular Pentavalent (Globo-H-GM2-sTn-TF-Tn) Immunization of Patients with Epithelial Ovarian, FT, or PP Cancer in 1st Remission

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A Phase I Study of Unimolecular Pentavalent (Globo-H-GM2-sTn-TF-Tn) Immunization of Patients with Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer in First Remission 

 Patient Characteristics

Twenty-four patients with advanced-stage, poor-risk ovarian carcinoma were enrolled on clinical trial NCT01248273 between 01/2011 and 09/2013. Patient characteristics are shown in Table 1. Patients had a median age of 54 years (range, 36–68 years). Primary sites included the ovary, 20; fallopian tube, three; and peritoneum, one. KPS ranged from 80–100%. The majority of patients were Caucasian (n = 22, 92%), and two patients were Asian (8%). Eighteen patients (75%) had stage III disease, and the remaining 6 (25%) had stage IV disease at diagnosis. Twenty-two patients (92%) had high-grade serous histology and two patients (8%) had clear cell histology.

 

3.4. Progression-Free Survival

Although clinical outcome was not the study end point of this phase I study, the PFS is illustrated in Figure 3. PFS was calculated for 20 events and censored at 24.6, 27, 42 and 46.5 months for four patients who continued in remission at last follow-up. The small patient numbers preclude any correlation of antibody response generated with PFS. It was observed that one of the patients with the longest PFS generated a response to all five antigens. At last follow-up, six patients had died of disease and the remaining 18 were alive. For this high-risk group, the median PFS was 12.6 months (95% CI, 10.2–29.5 months) from start of adjuvant chemotherapy.

  
5. Conclusions

The unimolecular vaccine was shown to be safe and immunogenic. Nine (75%) of 12 patients treated at the highest dose of 100 mcg and 20 (83%) of all 24 patients treated on the study responded to at least three antigens. This immune response was comparable to our previously reported immune response in a phase I trial of a heptavalent vaccine with individual antigens conjugated to KLH [13]. This unimolecular construct greatly simplifies manufacturing, permits the addition or exchange of multiple new antigens, and allows for easy scalability.