Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)

 Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial

Open access - The Lancet published December 17, 2015

Background
Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the effect of early detection by screening on ovarian cancer mortality.

Methods

In this randomised controlled trial, we recruited postmenopausal women aged 50–74 years from 13 centres in National Health Service Trusts in England, Wales, and Northern Ireland. Exclusion criteria were previous bilateral oophorectomy or ovarian malignancy, increased risk of familial ovarian cancer, and active non-ovarian malignancy......
 

Added value of this study

To our knowledge, this trial is the first randomised controlled trial of ovarian cancer screening to produce findings that show that in postmenopausal women from the general population, annual screening with use of the multimodal strategy is safe and could reduce deaths due to ovarian cancer. These findings are derived from one of the largest randomised trials ever done and renew hope that death rates from the most lethal of all gynaecological malignancies can be reduced through early detection.

Implications of all the available evidence

Our findings suggest that a multimodal approach to screening might detect ovarian cancer sufficiently early to reduce mortality. To establish the magnitude of this reduction in deaths, a longer duration of follow-up is needed. Meanwhile, efforts to refine ovarian cancer screening strategies should continue.

Final results of the UK Collaborative Trial of Ovarian Cancer Screening | Target Ovarian Cancer

In the news
 

Posted by Target Ovarian Cancer on Thursday 17 December 2015

 

The world’s largest research trial of its kind has today reported its final results, raising the prospect of a UK ovarian cancer screening programme at some point in the future. The UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) was coordinated by University College London and involved 200,000 women, 13 test centres throughout the UK and ran over 15 years......

In May 2015 the team released preliminary results about the performance of a new personalised CA125 blood test called ROCA which was used in one of the screening arms, although crucially this announcement did not address whether screening saved lives.
The UKCTOCS trial was only for women without symptoms of ovarian cancer and not at high risk of developing the disease due to a strong family history of either breast or ovarian cancer. Additionally, the trial was not assessing whether screening can be used to detect relapse in women who have already had ovarian cancer.
The final details of the trial were today published in The Lancet. Researchers say that the personalised blood test may help reduce the number of women dying from the disease by around 20 per cent, but stopped short of recommending that a screening programme for ovarian cancer would save lives. Not only was there not enough confidence that a screening programme would definitely impact mortality, but there are possible concerns around the number of women who would face unnecessary surgery or harm from surgical complications, which would need to be explored further......

Comparison of clinicopathologic variables in coexistence cancers of the endometrium and ovary: A review of 55 cases

abstract
  

BACKGROUND:

The coexistence primary cancers of the endometrium and ovary are relatively uncommon. The purpose of this study was to characterize patients diagnosed primary synchronous endometrial and ovarian cancer (SEOC), endometrial cancer (EC) with ovarian metastasis, and ovarian cancer (OC) with endometrial metastasis and compare clinicopathologic variables and prognosis.

MATERIALS AND METHODS:

All the patients with diagnosis of both endometrium and OC, who hospitalized between 2002 and 2012 in an academic center affiliated to Tehran University of Medical Sciences, were evaluated with respect to different clinicopathologic variables, follow-up times, and outcomes.

RESULTS:

Fifty-five patients had been diagnosed with both endometrium and OC. 17, 26, and 12 patients were diagnosed as SEOC, EC, and OC, respectively. The frequency of abnormal uterine bleeding was significantly lower in OC (16.7%) compared to others (58.8% in SEOC and 53.8% in EC). However, the abdominal/pelvic pain was significantly higher in OC (50%) compared to others (35.3% in SEOC and 34.6% in EC) (P < 0.05). Complex atypical hyperplasia (87.5%), endometriosis (88.8%), and endometrioid carcinoma (54.5%) was observed most in SEOC group. The duration of follow-up time was between 3 and 171 months with a mean of 16 months. There was no death in SEOC who followed. Survivals of patients between three group were statistically significant (P = 0.032).

CONCLUSION:

Our results showed that overall survival (OS) and progression-free survival (PFS) of SEOC patients is better than those with EC and OC (P = 0.032).

Bioidentical Hormones for Menopause: What Should We Tell Our Patients?

medscape

 The term "bioidentical" is not synonymous with "natural." "Bioidentical" refers to the structure of the product, whereas "natural" refers to its source and processing.

Lifetime use of nonsteroidal anti-inflammatory drugs and breast cancer risk: results from a prospective study of women with a sister with breast cancer

Full text

 The Sister Study (NCT00047970) is a prospective cohort of 50,884 women aged 35–74 years who had a sister with breast cancer but who did not have breast cancer themselves [18], [19].

Background

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to inhibit several pathways in experimental models of breast carcinogenesis, but epidemiological evidence remains insufficient to support their use for breast cancer prevention. We examined the association between use of NSAIDs and breast cancer risk in a prospective cohort.

Methods

The Sister Study is a prospective cohort study of women who had a sister(s) with breast cancer. As of December 2013, 2118 incident breast cancers were ascertained from 50,884 women enrolled between 2003 and 2009. Lifetime history of NSAID use was estimated from self-reported data in pill-years, with 1 pill per week for a year equivalent to 1 pill-year. Cox regression models were used to estimate hazard ratios (HRs) of breast cancer in relation to pill-years of use for different NSAIDs, with adjustment for potential confounders.....

How to Rationally Identify Promising Cancer Chemoprevention Agents

Commentary/Abstract (full text requires subscription $$)

 How to Rationally Identify Promising Cancer Chemoprevention Agents

There is no doubt that risk of many cancers is to a large extent modifiable. Not smoking will prevent a large number of human cancers, and vaccination for HPV infection protects against cervical and oropharyngeal cancers. Landmark migrant studies showed that moving from Japan to the United States reduced the risk of stomach cancer while increasing the risk of cancers of the breast, colon, and prostate. Results of epidemiological studies are strongly suggestive that certain micronutrients and food consumption patterns may prevent several cancer types. However, the results of randomized phase III trials testing these notions have been mostly disappointing, and some studies have even indicated harm.

Interfering with hormone action has provided a mechanism-based rationale for several phase III chemoprevention trials with antiestrogenic drugs for breast cancer and with 5α-reductase inhibitors for prostate cancer. While these studies have indicated efficacy of these agents, benefit may be restricted to certain cancer subtypes and side effects can occur. Antiestrogenic treatments are only indicated for women to prevent a second primary breast cancer and for women at high risk of a first breast cancer (1). However, antiestrogenic interventions are not generally used for the prevention of primary breast cancer (2,3), and the US Food and Drug Administration has not approved 5α-reductase inhibitors for the prevention of prostate cancer (4,5). Currently, there are no interventions with drugs or micronutrients for chemoprevention of primary cancers in the general population. It is thus …(Note: to read further requires $$)

Related articles

Article: Predictive Value Tools as an Aid in Chemopreventive Agent Development JNCI J Natl Cancer Inst (2015) 107 (12): djv259 doi:10.1093/jnci/djv259 
• Abstract
•  
 Background: Over 25 years, the National Cancer Institute’s Division of Cancer Prevention has entered some 800 agents into a chemopreventive agent testing program. Two critical steps involve: 1) in vitro/in vivo morphologic assays and 2) animal tumor assays (incidence/multiplicity reduction). We sought to determine how accurately the earlier-stage (morphologic) assays predict efficacy in the later-stage (animal tumor) assays.....

NCI’s New Tool Puts Cancer Risk in Context

open access
 

Type “cancer risk assessment” into Google, and you’ll come up with a list of assessment tools for particular cancers, most with a strong focus on personal risk factors related to lifestyle, exposures, and medical and family history.

Would it help also to get a broader view of cancer risk? The National Cancer Institute thinks so. NCI has teamed with Dartmouth researchers Steven Woloshin, M.D., and Lisa Schwartz, M.D., to create “Know Your Chances” (http://knowyourchances.cancer.gov/), a website that aims to put cancer risk in perspective.....

Genetic Test Finds Radiation Sensitivity Differs Between Primary Tumor and Metastatic Sites

open access

Genetic testing of tumors is driving personalized medicine in medical oncology. A recent study that used a molecular assay to assess the radiation sensitivity of primary tumors and metastases suggests potential for genetic testing in guiding radiation therapy as well.

The study, published July 15, 2015, in the International Journal of Radiation Oncology, Biology, Physics (doi:10.1016/j.ijrobp.2015.01.036), used a previously developed 10-gene assay to calculate a radiation sensitivity index (RSI).....

“Right now, we know clinically that patients have different responses to radiation, but the way we treat them doesn’t acknowledge that,” said study coauthor Javier F. Torres-Roca, M.D., a radiation oncologist at the Moffitt Cancer Center and Research Institute in Tampa, Fla. “Our focus is integrating genomic measures into radiation oncology, not only to understand the mechanisms of the problem but to find ways to treat patients more effectively.”.....

 In the new study, Torres-Roca and colleagues first calculated the RSI for 704 metastatic and 1,362 primary colon cancer lesions. Sixty percent of metastatic tumors were in the RSI radiation-resistant peak, compared with 54% of primary tumors, indicating the metastases might not respond as well to radiation therapy as the primary tumors. They also found statistically significant differences across metastatic sites, with metastases in the ovary and abdomen having the highest RSI scores (0.48 and 0.47, respectively), followed by liver, brain, lung, and lymph nodes (0.43, 0.42, 0.32 and 0.31 respectively)......

Efficacy of PD-1 blockade in tumors with MMR deficiency

open access

...As for the noncolorectal patients, the path toward development may have to follow traditional histology based clinical trials, however, this approach for multiple, rare diseases would be cumbersome and resource intensive. As we get more experience with various diseases, a more forward-thinking approach for drug development would allow targeting of mismatch repair deficiency across tumor types in a molecularly-targeted, tissue agnostic treatment strategy. Even if only 5% of cancers across the world were mismatch repair deficient, this would bring a new treatment option with prolonged benefit to many individual patients

Tie between estrogen, memory explored by researchers (in mice)

science news article


Journal Reference:

1. Anna Phan, Sarah Suschkov, Luke Molinaro, Kathryn Reynolds, Jennifer M. Lymer, Craig D. C. Bailey, Lee-Ming Kow, Neil J. MacLusky, Donald W. Pfaff, Elena Choleris. Rapid increases in immature synapses parallel estrogen-induced hippocampal learning enhancements. Proceedings of the National Academy of Sciences, 2015; 201522150 DOI: 10.1073/pnas.1522150112

From the Editor-In-Chief The Immune System and Cancer (focus on Lynch Syndrome)

Cancer Today (short article)

.... Although in HNPCC (Lynch Syndrome), each mismatch mistake rarely causes a gene defect that can fuel cancer development, the sheer quantity of mismatch errors increases the chance that cancers will appear in people with the condition.......HNPCC cancers appear to be readily recognized not just as “nonself,” but as markedly different from “self.”

 

This is a stunning advance in treatment for those who have HNPCC cancer. Hopefully, immune responses for non-HNPCC cancers—the majority of cancer cases—can also be better understood. In this way, the immune system can be helped not only to recognize all cancer cells as “nonself,” but also to destroy them.

Cancer Survivorship Symposium - conference notice - Jan 2016

Cancer Survivorship Symposium

 

Discover the Latest in Survivorship Research: Abstract Titles Released

See Abstract Titles

Preview the science that will be presented at this year’s Symposium by reviewing the full list of abstract titles

It’s Not Too Late to Register

 

View Registration Details

Your registration fee not only includes access to the Symposium, but also includes Virtual Meeting, which allows access to Symposium presentations and posters.

An Evening for Cancer Survivors and Caregivers

Learn More

We invite survivors and caregivers to join us for a free reception, panel discussion, and Q&A featuring survivorship experts on January 14.

Cancer incidence and survival in Lynch syndrome patients.....

open access: Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database

 Significance of this study

What is already known on this subject?

• Inherited colorectal cancer may be caused by mismatch repair gene mutations and is then commonly referred to as Lynch syndrome.
• Lynch syndrome is under-recognised and results in about 0.1% of the population having a significantly increased risk of early onset colorectal, endometrial and ovarian cancer.
• Endoscopic surveillance with removal of precursor adenomas is recommended to prevent colorectal cancer.

What are the new findings?

• This is the first comprehensive prospective study to provide empirically observed data on colorectal cancer incidence and survival in Lynch syndrome.
• Colorectal cancer occurred despite colonoscopic surveillance with removal of adenomas.
• Colonoscopic surveillance with early detection and treatment of invasive colorectal cancer was associated with excellent survival. Survival after first endometrial or ovarian cancer was also excellent.
• Revised estimates of the different penetrance and expression patterns in carriers of MLH1, MSH2, MSH6 and PMS2 mutations. 
  
  
   Survival
  Overall 5-year and 10-year survival were excellent, reflecting survival for the most frequent cancers, CRC and endometrial cancer (table 7). Ovarian cancer survival also appeared to be excellent in LS patients, although the small number of cases adds uncertainty to the observation. A majority of patients also achieved 10-year survival of upper GI and urinary tract cancers, although survival rates were not as good as for the other cancers. 
  
  
  View this table:

  • In this window
  • In a new window
  Table 7
  5-year and 10-year crude survival after first cancer diagnosed by cancer type in Lynch syndrome (LS) patients without prior or prevalent cancer at first colonoscopy 
  
  
  
  
  Table 7

  5-year and 10-year crude survival after first cancer diagnosed by cancer type in Lynch syndrome (LS) patients without prior or prevalent cancer at first colonoscopy

  Group	Number cases	5-year survival (95% CI)	10-year survival (95% CI)
  Any cancer	301	90% (86 to 93)	87% (83 to 91)
  Colorectal cancer	140	94% (90 to 98)	91% (84 to 95)
  Endometrial cancer	71	98% (88 to 99.8)	98% (88 to 99.8)
  Ovarian cancer	19	88% (60 to 97)	89% (60 to 97)
  Upper GI cancer	24	58% (36 to 75)	53% (31 to 71)
  Urinary tract cancer	17	82% (51 to 93)	73% (42 to 89)

Ovarian metastasis of the breast cancer : A Case Report

Case Report (Morocco)

Letter From the Editor : International Journal of Gynecological Cancer

Letter From the Editor 

 The theme we have chosen for all the 2016 volumes is “compassion” and calls attention to this much deserved issue, which is such a great part of the practice of gynecological oncology.

Staging Lymphadenectomy in Patients With Clear Cell Carcinoma of the Ovary

open access

 Objective: The purpose of this study was to assess the rate of lymph node (LN) metastasis in comprehensively staged ovarian clear cell carcinoma (OCCC) clinically confined to the ovary and determine factors associated with LN metastasis.

Current Issue : International Journal of Gynecological Cancer

Index (subscription based = $$ - some exceptions with access to full text)

Table of Contents Sections

• Editorial
• Esgo
• Letters to the Editor
• Review Article
• Ovarian Cancer
• Uterine Cancer
• Cervical Cancer
• Cooperative Groups
• Gestational Trophoblastic Neoplasia

Comparing Gene Expression Data From Formalin-Fixed, Paraffin Embedded Tissues and qPCR With That From Snap-Frozen Tissue and Microarrays for Modeling Outcomes of Patients With Ovarian Carcinoma

open access print version - Medscape (Wisconsin) 
 Comparing Gene Expression Data From Formalin-Fixed, Paraffin Embedded Tissues and qPCR With That From Snap-Frozen Tissue and Microarrays for Modeling Outcomes of Patients With Ovarian Carcinoma

 Background
Using gene expression and clinical data from The Cancer Genome Atlas (TCGA), we previously developed a model that predicts variations in response of high-grade serous ovarian cancer to cytotoxic chemotherapies. In that publication,^[1] we described a method for reducing the list of genes needed to predict clinical outcomes to fewer than 100. We selected those genes from more than 10,000 possibilities by identifying genes within a core group of 12 cancer pathways^[2,3] whose variation in expression had the greatest effect on disease progression. Predictions of response to specific chemotherapeutic agents were suggested by the cumulative levels of gene expression among the 91 genes selected from the 12 pathways. Three of the pathways did not have genes identified, leaving 9 core pathways informative. We defined the predictions made by gene expression within these pathways as the Patient-Specific Risk Profile (PSRP)......

Gene List
The genes whose expression we assayed were selected from a gene set constituting the 9 core pathways described previously.^[1] 91 genes were chosen from our previously published PSRP results. Analysis was performed according to the 9 core pathways as well as a revised six-gene set representing the neurotrophin pathway, making a total of 10 pathways available for analysis (Additional file 1: Table S1 http://www.biomedcentral.com/1472-6890/15/17/additional). The subsets of genes used to define a pathway's expression are listed in the Supplement as well (Additional file 1: Table S2 http://www.biomedcentral.com/1472-6890/15/17/additional). We used the housekeeping genes glyceraldehyde 3-phosphate dehydrogenase (GAPDH), hypoxanthine phosphoribosyltransferase 1 (HPRT1), and beta-D-glucuronidase (GUSB) to normalize gene expression.

In summary, this study validated the use of FFPE tissue and qPCR—instead of snap-frozen tissue and microarrays—to obtain gene expression data for core cellular pathways. This supports the use these tissue samples when predictive modeling of ovarian cancer was done in larger data sets such as the TCGA. The variation in expression noted between our different samples does not appear to significantly distort expected outputs, leading us to believe that a model derived from expression reported using one approach could be used with a more convenient and "real world" approach when evaluating clinical samples. Our assay will be tested in a recurrent disease setting to more definitively evaluate predictive capacity prospectively.

(U.S.) Georgia Primary Care Providers’ Knowledge of Hereditary Breast and Ovarian Cancer Syndrome

Georgia 

Hereditary breast and ovarian cancer syndrome (HBOC) is an inherited condition associated with mutations in the BRCA1 or BRCA2 (BRCA) genes. Identification of individuals with HBOC requires that primary care providers understand the genetic principles required to appropriately collect family history and refer individuals for genetic evaluation. A survey was developed and administered to primary care providers in Georgia to assess their existing knowledge of HBOC and direct targeted educational efforts.

We found that Georgia providers demonstrate some knowledge of basic genetic principles but were unable to consistently identify individuals at risk for HBOC. Knowledge deficits included lack of understanding of inheritance patterns and failure to recognize the significance of ovarian cancer history. Strategies for improving identification of patients with HBOC include increasing provider knowledge and integrating HBOC risk assessment tools into practice. Identification of individuals at risk is the critical first step in the process of reducing incidence of breast and ovarian cancer associated with BRCA mutations.

Review: Opportunistic salpingectomy for ovarian cancer prevention

Open access

 In summary, opportunistic salpingectomy is a safe intervention in the short term, when done concurrently with hysterectomy or instead of tubal ligation. It has the potential to reduce the incidence and mortality from ovarian cancer, and it may have an important role as a temporizing measure in high-risk women with BRCA mutations who are unwilling to undergo standard risk reducing surgery (bilateral salpingo-oophorectomy) at an early age. It will still be essential to evaluate long-term safety and efficacy outcomes to support the ongoing use of this intervention in the general population as well as the high-risk setting.

Full predicted energy from nutrition and the effect on mortality and infectious complications in critically ill adults

open access
 

Protocol

Full predicted energy from nutrition and the effect on mortality and infectious complications in critically ill adults: a protocol for a systematic review and meta-analysis of parallel randomised controlled trials

Background

Nutrition is vital to survival in health. In critical illness, however, the role of nutrition is less defined. More specifically, the exact amount of energy that is required during critical illness to optimally influence clinical outcomes remains unknown. Prolonged provision of nutrition below a patient’s individual nutrition requirements (including under provision of energy, specifically) can result in malnutrition. Whist the prevalence of malnutrition in critically ill patients is generally poorly documented, poorly defined, and varies depending on the criteria used, reports indicate that worldwide prevalence in hospitalised patients is between 20 and 50 % internationally [1]. Malnutrition is thus likely to be commonplace in critically ill patients. In the acute hospitalised population, malnutrition has been associated with many undesirable clinical consequences such as reduced immune function, increased length of hospital stay, impaired wound healing, muscle wasting and ultimately increased health care costs [1]. Conversely, it is known that excessive nutrition can lead to over provision of energy and result in adverse patient effects including increased metabolic stress, hyperglycaemia and deranged liver function [2].

Despite the known consequences of significant under- or overfeeding in critically ill patients, there is considerable uncertainty.....

Expected benefits of this review

This will be the first published systematic review and meta-analysis to our knowledge that will investigate the effect of delivering full predicted energy from nutrition on clinical outcomes in critically ill adults, compared to delivering less than full predicted energy requirements. The literature available on this topic is conflicting and confusing for clinicians and could potentially lead to misleading conclusions being made regarding the role of nutrition in critical illness. This systematic review and meta-analysis will benefit clinicians by providing a summary of the available literature and provide further guidance.

Oncofertility in Gynecologic Malignant Tumors

Open access  (pdf)

Long-term survival is the priority in treatment of patients with malignant tumors. In the field of gynecology, fertility preservation has also recently become an important objective due to improved treatment outcomes and different needs of patients. Methods for fertility preservation include cervical conization, ovarian protection against radiation or chemotherapy for ovarian cancer since the ovary is hypersensitive to cancer therapies, treatment of gynecological cancer during pregnancy, and cryopreservation of oocytes, embryos or ovarian tissue before treatment of malignant tumors. Radical trachelectomy for early cervical cancer and treatment with medroxy progesterone acetate for early endometrial carcinoma are also options for fertility preservation, but the efficacy and risk of recurrence have yet to be fully evaluated. The first childbirth following uterine transplantation was also achieved last year and this success has expanded the potential for pregnancy and delivery among cancer survivors.

Race and colorectal cancer screening compliance among persons with a family history of (any) cancer

 Blogger's Note: 'any' type of cancer is not detailed (generalized into 1 category - Y vs. N))

open access

- We hypothesized that CRC awareness should be higher among families with any history of cancer, not just CRC.
-  We are not aware of any other study that has examined the association of a family history of any cancer with CRC screening for a direct comparison to our study.

AIM: To determine compliance to colorectal cancer (CRC) screening guidelines among persons with a family history of any type of cancer and investigate racial differences in screening compliance.

 Core  tip:
It  is  unclear  whether  suboptimal  screening  contributes  to  the  increased  risk  of  cancer  within  families.  We  evaluated  compliance  with  colon  cancer
screening guidelines among adults in the United States.
Our study suggested that adults with a family history of  any cancer had higher screening rates, but the  smallest  increase  was  noted  among  blacks.
Overall,  screening  was  lower  among  blacks  and  Hispanics  to  such  an  extent  that  screening  among  those  with  a  family  member  with  cancer  was  not  higher  than  screening  among  whites  without  a  family  member  with  cancer.
There is a particular need to improve screening among  high risk blacks.

Long anticipation complicates identifying Lynch Syndrome in monozygotic twins (& mother/MLH1)

abstract (case report)

Anticipation is a term used to express an earlier age of disease onset in successive generations. Patients with Lynch syndrome (LS) harbor mutations in MMR genes that appear to be associated with the phenomenon where disease is diagnosed 5–12 years earlier in mutation carrying children compared with their affected parent. This has the potential to complicate the recognition of LS as defined by the Amsterdam criteria (or iterations of it) in young probands affected by colorectal cancer. In this report, we describe a case of an LS family with an MLH1 mutation (c.1748 del T). The phenomenon of anticipation was observed in the son of a monozygotic twin who developed two colon cancers that were diagnosed at an age 20 years earlier than the first diagnosis of cancer in his mother. Both the mother and her twin went on to simultaneously develop a rectal carcinoma.

The Significant Prognosticators of Upper Tract Urothelial Carcinoma - Review

Blogger's Note:  this review is not specific to genetics pre-disposition (eg. Lynch syndrome)

open access

 (Surgical section)  In conclusion, RNU with bladder cuff excision has to be considered the gold standard treatment of UTUC regardless of the tumor location and stage. Although laparoscopic approaches have been described, further advanced or large studies should be performed to confirm the results.

Article Outline

1. 1. Introduction
2. 2. Materials and methods
3. 3. Results
   1. 3.1. Clinicopathological characteristics
      1. 3.1.1. Chronic kidney disease
      2. 3.1.2. Sex
      3. 3.1.3. Previous/synchronous bladder tumor
      4. 3.1.4. Tumor location
   2. 3.2. Surgical factors
      1. 3.2.1. Types of surgery
      2. 3.2.2. Bladder cuff management
   3. 3.3. Molecular markers
      1. 3.3.1. p53
      2. 3.3.2. Glutathione S-transferase
      3. 3.3.3. Cyclooxygenase-2
      4. 3.3.4. TG-interacting Factor
      5. 3.3.5. Nuclear factor-κB
      6. 3.3.6. Hypoxia-inducible factor-1
      7. 3.3.7. Osteopontin
4. 4. Conclusion
5. Conflicts of Interest
6. Sources of Funding
7. References

Long-term Survivors After Liver Resection for Ovarian Cancer Liver Metastases (open access)

open access  (small study 8 patients)

 Conclusion: In selected cases liver resection for ovarian cancer liver metastases can be associated with a significant increase of the overall survival.

Fallopian tube organoids promise better understanding of ovarian cancer, infertility

medical news

 A new way of growing fallopian tube cells in culture is expected to give a boost to our understanding and prevention of female genital diseases, such as infertility, inflammatory disease, and ovarian cancer.


Journal Reference:

1. Mirjana Kessler, Karen Hoffmann, Volker Brinkmann, Oliver Thieck, Susan Jackisch, Benjamin Toelle, Hilmar Berger, Hans-Joachim Mollenkopf, Mandy Mangler, Jalid Sehouli, Christina Fotopoulou, Thomas F. Meyer. The Notch and Wnt pathways regulate stemness and differentiation in human fallopian tube organoids. Nature Communications, 2015; 6: 8989 DOI: 10.1038/NCOMMS9989

Discount sways U.K. cost gatekeeper on AstraZeneca's ovarian cancer med Lynparza - FiercePharma

U.K. 

December 11, 2015

AstraZeneca ($AZN) scored a victory for its ovarian cancer drug Lynparza, as U.K. cost watchdog the National Institute for Health and Care Excellence (NICE) did an about-face and recommended the med for some patients as long as the company offers a discount.

The notoriously tough cost gatekeeper gave a thumbs-up to Lynparza in final draft guidance but attached a few conditions to its approval. Patients taking the med must have BRCA1 or BRCA2 mutations and have already had three or more rounds of platinum-based chemo. The agency is also requiring that AstraZeneca pay for treatment if patients remain on the drug longer than 15 months, the PharmaTimes reports.

NICE rejected Lynparza over the summer after finding that its £4,200-a-month price didn't justify its benefits, sparking backlash from the company and physicians who wanted patients to have access to the innovative drug. Lynparza is part of a new class of treatments, poly ADP-ribose polymerase (PARP) inhibitors, which target cancer cells while leaving patients' normal cells untouched.

Statistical controversies in clinical research: end points other than overall survival are vital for regulatory approval of anticancer agents

abstract

There is an ongoing debate about the relative merits of overall survival (OS) and other metrics that can be used as primary end points in cancer clinical trials. Although survival time is arguably the most objective metric for assessing the efficacy of anticancer treatment, OS as a clinical-trial end point needs to be conceptually distinguished from increased survival time as a goal desired by patients, clinicians and public-health policy makers. OS presents several drawbacks as a primary end point that threatens to hamper further drug development, including the increase in the number of patients and the much longer follow-up required in a clinical trial. In many settings of first-line therapy for metastatic disease, median OS is currently two to four times longer than median progression-free survival. As a result, the analysis of OS may be increasingly confounded by the effect of salvage therapies used after disease progression. In this review, we use straightforward statistical reasoning and examples from the oncology literature to argue that OS should no longer be the primary end point of most future phase III cancer clinical trials that aim at assessing the efficacy of novel therapies in the setting of metastatic disease.

Regional anaesthesia and analgesia: relationship to cancer recurrence and survival (immune system...)

open access

Editor's key points

• Considerable evidence suggests that anaesthesia can have both direct and indirect effects on cancer cell survival and metastasis.
• Small retrospective clinical trials suggest that regional anaesthesia is associated with improved survival in cancer surgery.
• Large randomized clinical trials comparing the effects of regional and general anaesthesia on long-term outcome after cancer surgery are necessary to guide clinical practice.

Online CME & CE courses: Case Challenges in Opioid-induced Constipation

Online CME & CE courses 

The Origin of Epithelial Neoplasms of the Ovary: An Alternative View

abstract

 Several theories have been proposed to explain the origin of epithelial neoplasms of the ovary. However, most of them did not receive serious consideration until recently when it has been proposed that most ovarian neoplasms arise from the fallopian tube. In this review, we mention the different theories, we discuss in detail the fallopian tube theory, and the reasons why this theory is probably inaccurate. We are also proposing a new theory, the fere ex nihilo, based on the observation of numerous cases, old and new concept, and experimental works with animals. We believe that, most probably, ovarian epithelial neoplasms are related to hormones and the identification of these hormones will allow us not only to diagnose and treat these lethal neoplasms, but also to prevent them.

U.S. FDA Grants Orphan Drug Designation to TapImmune’s TPIV 200 in the Treatment of Ovarian Cancer

Pharma website news

 ion to TapImmune’s TPIV 200 in the Treatment of Ovarian Cancer

10 Dec 2015

Company preparing for Phase II ovarian cancer trial based on positive data in Mayo Clinic Phase I trial

JACKSONVILLE, Florida, December 9, 2015 /PRNewswire/ –
TapImmune, Inc. (TPIV), a clinical-stage immunology-oncology company specializing in the development of innovative peptide and gene-based immunotherapeutics and vaccines for the treatment of cancer & metastatic disease, announced today that it has received Orphan Drug Designation from the U.S. Food & Drug Administration’s Office of Orphan Products Development (OOPD) for its cancer vaccine TPIV 200 in the treatment of ovarian cancer. The TPIV 200 ovarian cancer clinical program will now receive benefits including tax credits on clinical research and 7-year market exclusivity upon receiving marketing approval.

 TPIV 200 is a multi-epitope peptide vaccine that targets Folate Receptor Alpha which is overexpressed in multiple cancers including over 90% of ovarian cancer cells.  In Phase I clinical studies conducted at the Mayo Clinic in patients with breast and ovarian cancer this vaccine was shown to be safe and well tolerated and to give robust cellular immune responses in 20 out of 21 evaluable patients.  Further, the data showed that 16 out of 16 patients in the observation stage still showed immune responses. Data from the Phase I studies were published in the Journal of Clinical Oncology covering the American Society of Clinical Oncology meeting in May 2015.   Multiple Phase II studies will examine the efficacy of this vaccine in ovarian and triple negative breast cancer.....

Health Care Wait Times - What is the Real Story? - Ontario Health Coalition (Fraser Institute findings....)

What is the Real Story?

 
Posted: December 8, 2015

By: Natalie Mehra, Executive Director, Ontario Health Coalition

 

Today, a high-profile report tracking health care wait times was released from the Wait Times Alliance. Eliminating Code Gridlock in Canada’s Health Care System, is a credible summary and a useful addition to public policy decisions about health care planning. It is written by an alliance of physician specialists’ organizations to track progress in wait times and public reporting.

Leeching off of the publicity for the day, the Fraser Institute — a pro-privatization think-tank (see Who Funds the Fraser Institute? here and here) — also released their annual wait times report. Releasing this report at the same time as the release of the Wait Times Alliance Report may garner extra media, but it is bound to cause confusion.

Both reports are about wait times in health care. But the similarities stop there.

The methodology of the Fraser Institute is based on the subjective viewpoints of the small proportion of physician specialists who answer their surveys. If you read the methodology section of their report, you will find that their response rate is only 21%. That is, they received answers from just one in five of the physicians they surveyed.The Fraser Institute uses a number of different methods to take these survey results and turn them into the median (middle) wait times that they report nationally and for each province.....

EJHG - Attitudes of nearly 7000 health professionals, genomic researchers and publics toward the return of incidental results from sequencing research

European Journal of Human Genetics - open access

Ovarian Cancer Treatment and Survival Trends Among Women Older Than 65 Years of Age in the United States, 1995-2008

abstract
 

OBJECTIVE:

To evaluate whether overall survival is improving among women in the United States with advanced ovarian cancer.

METHODS:

This retrospective cohort study evaluated trends in treatment and overall survival for women older than 65 years diagnosed with stage III and IV epithelial ovarian cancer between 1995 and 2008 using Surveillance, Epidemiology, and End Results-Medicare data. Parametric and semiparametric multivariate survival analyses were used to assess comparative treatment survival rates and factors affecting survival and recurrence.

RESULTS:

Of 7,938 women who met study criteria, 2.9% received no treatment, 15.4% underwent surgery only, 24.8% received chemotherapy only, 41.8% underwent primary debulking surgery and chemotherapy in an optimal timeframe, and 15.1% had primary debulking surgery and chemotherapy, but the timing was not optimal or patients did not complete all six cycles of chemotherapy. Those who underwent surgery only had similar survival as those who received no treatment (2.2 compared with 1.7 months), whereas those who received chemotherapy only had a better overall survival (14.4 months). Optimal treatment was associated with the longest survival time (P<.001, median overall survival 39.0 months). Additionally, survival time associated with optimal treatment increased over the past decade. However, the proportion of women who received optimal treatment has decreased over the past decade.

CONCLUSION:

Elderly women with advanced ovarian cancer have the best survival with optimal therapy. When this is not offered or possible, chemotherapy alone offers better survival than surgery alone.

Does happiness itself directly affect mortality? The prospective UK Million Women Study

Abstract - The Lancet

 Summary - Background
Poor health can cause unhappiness and poor health increases mortality. Previous reports of reduced mortality associated with happiness could be due to the increased mortality of people who are unhappy because of their poor health. Also, unhappiness might be associated with lifestyle factors that can affect mortality. We aimed to establish whether, after allowing for the poor health and lifestyle of people who are unhappy, any robust evidence remains that happiness or related subjective measures of wellbeing directly reduce mortality.....

also:
media item 

......A complicated question of health and happiness

The study authors reached their conclusions by essentially excluding people who were unhappy and in poor health. They explain that unhappy people who suffer from illness, smoke or who are inactive, for instance, feel unhappy because of their health.

But excluding those people is a mistake, argues Timothy Lau, clinical lead of the geriatric program at the Royal Ottawa Mental Health Centre. The people who rated themselves as unhappy during the study who suffered poor health could have been unhappy long before those physical ailments began, he explained. In other words, people who are unhappy for a long time may develop health problems. This study didn’t properly address that issue, he said......

Multi-Gene BRCA Testing Identifies Mutations Other than BRCA

oncology news

....A total of 39 patients (4.0%) had a VUS in a BRCA1 or BRCA2 gene, with little difference between those who underwent multi-gene screening or limited testing. However, among women who underwent multi-gene panel testing, an additional 3.9 percent harbored non-BRCA pathogenic mutations and 10.1 percent had a non-BRCA VUS.....

ASCO/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline

open access

SMAC mimetic Debio 1143 synergizes with taxanes, topoisomerase inhibitors....

open access
  SMAC mimetic Debio 1143 synergizes with taxanes, topoisomerase inhibitors and bromodomain inhibitors to impede growth of lung adenocarcinoma cells

.... We describe here the potential utility of Debio 1143 in combination with taxanes, topoisomerase inhibitors, or bromodomain inhibitors. The combination of Debio 1143 with both paclitaxel and carboplatin is in clinical trials for lung squamous cell carcinoma, platinum-refractory ovarian carcinoma, and triple negative breast cancer (NCT01930292)......


Reference: (ovarian cancer)
  18. Thibault BG, L.; Broca, C; Barbier, M.; Zanna, C.; Vuagniaux, G.; Delord, J-P.; Couderc, B. (2015). The IAP inhibitor Debio 1143 reverses carboplatin resistance in ovarian cancer cells by inducing both apoptosis and necroptosis. AACR Annual Meeting 2015.

European Medicines Agency (EMA) grants Orphan Drug Designation for Debio 1143 (ovarian cancer)

pharma news

The European Medicines Agency (EMA) has granted Orphan Drug Designation to Debiopharm International‘s Debio 1143 for treatment of ovarian cancer.

NCI Visuals Online: Classic Lynch Syndrome pedigree

NCI Visuals Online: Image Details

 Lynch syndrome pedigree. This pedigree shows some of the classic features of a family with Lynch syndrome, including affected family members with colon cancer or endometrial cancer and a younger age at onset in some individuals. Lynch syndrome families may exhibit some or all of these features. Lynch syndrome families may also include individuals with other gastrointestinal, gynecologic, and genitourinary cancers, or other extracolonic cancers. As an autosomal dominant syndrome, Lynch syndrome can be transmitted through maternal or paternal lineages, as depicted in the figure.

 

NCI Visuals Online: Classic BRCA 2 pedigree

NCI Visuals Online: Image Details

 

NCI Visuals Online: Classic BRCA1 pedigree

NCI Visuals Online: Image Details
 

Whose Death Is It Anyway? Perspectives on End-of-Life in Canada (2 high-profile Canadian physicians)

open access


...One week after a CT scan revealed he had a midbrain tumour, Dr. Donald Low began talking with his wife, Maureen Taylor, about assisted dying. As an internist and microbiologist for almost 40 years, Low knew the tumour was virtually untreatable, and that the end would be messy. While he allowed his physicians to steer him towards a biopsy, a ventriculoperitoneal shunt, chemotherapy and radiation, he never let himself or his family be lulled into a sense of false hope. For seven months, Low and Taylor researched the means that would provide him with a peaceful death, in his own home, at the time of his choosing. But even with Low’s connections in the international medical community, and despite his access to potent drugs, Low died the death he feared: paralyzed, unable to communicate with his family, sedated so that he could tolerate the intolerable. 

Why make people suffer for no reason, when there’s an alternative? asked Low in a video interview taped eight days before his death (Cancer View Canada 2013). A lot of clinicians have opposition to dying with dignity. I wish they could live in my body for 24 hours, and I think they would change that opinion. 

While Low was dealing with his terminal brain cancer in the winter and spring of 2013, his Mount Sinai Hospital colleague, Dr. Larry Librach, was even closer to death. One of Canada’s leading palliative care specialists, Librach died of pancreatic cancer in August, peacefully and at home, according to his family. Although he advocated for improved palliative care for all patients at the end of life, and would not have chosen an assisted death for himself, Librach believed that palliative care would not suffice for a minority of dying people. 
Even before his own diagnosis, Librach was an expert witness at the British Columbia Supreme Court in a legal challenge to the prohibition against medically assisted suicide. There were several plaintiffs, including Gloria Taylor, a B.C. woman suffering from amyotrophic lateral sclerosis (ALS). Librach later told CTV News (2013), “The best of palliative care will still not prevent people, like Gloria Taylor, from saying, that’s great, but I still want control over the end of my life. And I don’t see that there’s any ethical or other reason why we shouldn’t allow that when there are appropriate safeguards.” ......

Waiting Your Turn: Wait Times for Health Care in Canada, 2015 Report

Fraser Institute Report pdf

(U.S.) FDA allows marketing of cooling cap to reduce hair loss during chemotherapy

U.S. - medical news

 December 8, 2015 -- Today, the U.S. Food and Drug Administration cleared for marketing in the United States the first cooling cap to reduce hair loss (alopecia) in female breast cancer patients undergoing chemotherapy.....

JCO The Art of Oncology: Making Peace With Cancer (oncologist/ovarian cancer/PD-L1)

open access

..... As an oncologist, I read Journal of Clinical Oncology (JCO) with feelings of pride and empathy. I am proud of my own articles in JCO, but during the last few months, I have not been able to touch it. Why? If you change sides of the bed—moving from physician to patient—you begin to change your style of reading. I realized today that I was more interested in the Art of Oncology articles than in the Original Report articles. I realized that except for stories of pediatric oncologists who lose children to cancer, few if any of the Art of Oncology articles seemed to tell the story of an oncologist with cancer. Does this mean it is unprofessional to get cancer? Or that it is unprofessional to write about that experience?....

Treosulfan in the Treatment of Advanced Ovarian Cancer

abstract
 

PATIENTS AND METHODS:

Two hundred and forty-eight ovarian cancer patients in 57 Centers, who received treosulfan mainly either i.v. (5,000-8,000 mg/m(2) d1, q21d or q28d) or p.o. (400-600 mg/m(2) d1-14 or 21, q28d) for at least one therapy cycle were evaluable and were included in the study.

RESULTS:

With a median age of 70 years (range=36-92 years), predominantly elderly patients received treosulfan treatment. Most participants presented serous histology (131, 52.8%) and advanced-stage FIGO III (122, 49%) or IV (55, 22%) disease. Median ECOG status was 1 (range=0-2), whereas cardiac co-morbidity was common (31%). Treosulfan was usually administered as second- (26%), third- (21%) or fourth-line (17%) therapy. Two hundred and one patients received i.v. and 47 p.o.

TREATMENT:

The most common reason for dose modifications was due to hematological toxicity (46%). The main reason for a therapy discontinuation was progressive disease (38.5%). Response was observed in 25.8% of participants, disease stabilization in 28.6 % and progress in 45.6%. The median progression-free and overall survival was 196 and 405 days, respectively.

CONCLUSION:

In predominantly elderly and heavily pre-treated patients with recurrent ovarian cancer, treosulfan featured a clinical relevant efficacy and well-manageable, mostly hematological, toxicity, which resulted in a positive therapeutic index.

Using patient-reported outcome measures as quality indicators in routine cancer care

Editorial

 Historically, patient-reported outcome measures assessing symptoms and physical functioning have not been included in quality-of-care assessments. This editorial accompanies Smith et al's article on the innovative Patient Reported Outcomes Symptoms and Side Effects Study methodology using the Commission on Cancer's Rapid Quality Reporting System, and it explores methodological advancements needed before patient-reported outcome measures can be used as quality-of-care metrics.