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Monday, January 30, 2012

Medical Information for Children - Medikidz Comic Book Store (brain tumour as an example)



 

What's Up with Rachel 

(brain tumour as an example)

Medikidz explain cancer

Medikidz explain…
Medikidz Ltd, Sept 2009—Jan 2012
 
32 pp per book, £6.99. http://www.medikidz.com/
 
The Medikidz are a gang of superheroes with a mission—to explain medical information to children in plain language. In a series that includes titles such as What's up with Lyndon? Medikidz explain osteosarcoma , these five superheroes help kids understand brain tumours, melanoma, and several other types of cancer that affect children and families. Each 32-page book is designed as a graphic novel with vibrant illustrations and recurring themes and characters to keep kids engaged with the medical co ...

Medical paternalism: who knows best? : The Lancet Oncology



open access: Commentary: VEGF Trap for the treatment of malignant ascites : The Lancet Oncology



"About 10% of all cases of ascites are caused by a malignant disease. In developed countries the most common neoplasm associated with ascites is ovarian cancer. The pathophysiology of malignant ascites is multifactorial, and its molecular pathogenesis is only poorly understood. Ascites formation can result from obstruction of lymph vessels by tumour cells, resulting in incomplete absorption of intraperitoneal fluid and protein,1 especially in patients with lymphoma or breast cancer. Since malignant ascites is usually an exsudate with a high protein concentration, an increased vascular permeability has been implicated in its pathogenesis.2 In addition to mechanical obstruction and cytokines, the pathophysiology of malignant ascites includes hormonal mechanisms. Because of the accumulation of ascites caused by obstructed lymph vessels, the circulating blood volume is reduced, which results in activation of the renin-angiotensin-aldosterone system that is followed by sodium retention.
Unlike the established therapeutic options for the underlying malignancy, there is no generally accepted gold standard for the management of malignant ascites...."

"...With respect to the clinical implications of the results (Walter Gotlieb and colleagues7 in The Lancet Oncology), symptom relief has to be weighed against discomfort and potentially life-threatening adverse events (three patients had fatal gastrointestinal complications in the aflibercept group vs one in the placebo group), since the treatment is applied to patients in a highly palliative situation. Careful patient selection could reduce the incidence of gastrointestinal perforations. However, before a general recommendation of aflibercept for the treatment of malignant ascites can be made, further studies, including comparative effectiveness research,8 are needed to compare the effectiveness of the different therapeutic strategies in daily clinical practice."

Assessment of symptomatic women for early diagnosis of ovarian cancer: results from the prospective DOvE pilot project : The Lancet Oncology



"....Seven (78%) of the HGSC in the DOvE group originated outside the ovaries and five were associated with only slightly raised CA-125 concentrations and minimal or no ovarian abnormalities on TVUS."

 

Interpretation

The proportion of HGSC that originated outside the ovaries in this study suggests that early diagnosis programmes should aim to identify low-volume disease rather than early-stage disease, and that diagnostic approaches should be modified accordingly. Although testing symptomatic women may result in earlier diagnosis of invasive ovarian cancer, large-scale implementation of this approach is premature.

Intravenous aflibercept for treatment of recurrent symptomatic malignant ascites in patients with advanced ovarian cancer: a phase 2, randomised, double-blind, placebo-controlled study : The Lancet Oncology



open access: Editorial - Ovarian cancer: breaking the silence : The Lancet Oncology (references Avastin studies and NEJM)



Ovarian cancer: breaking the silence

 
"The heterogeneous nature of cancer makes it a very difficult disease to manage. Although great progress has been made against many types of cancer (as highlighted by recent mortality data from the American Cancer Society), treatment of others has shown little change in the past few decades. Ovarian cancer, for example, has traditionally lagged behind: recent research, however, is starting to provide a better outlook for women with this cancer. Two phase 3 clinical trials published in December, 2011, in the New England Journal of Medicine (GOG018 and ICON7) showed that women with newly diagnosed advanced ovarian cancer given concomitant bevacizumab with a paclitaxel and carboplatin chemotherapy regimen following surgery, and then maintenance bevacizumab, had significantly longer progression-free survival compared with those who received chemotherapy alone. On the basis of these results, on Dec 19, 2011, the European Medicines Agency approved bevacizumab for first-line treatment of ovarian cancer, although it is uncertain whether the US FDA will follow suit....."

"Ovarian cancer is the seventh most common cancer in women worldwide, with nearly a quarter of a million women diagnosed every year. 5-year survival is just 30%, a figure that has not changed for the past 30 years—this contrasts with breast cancer, in which 5-year survival has improved from 50% to 80% over the same period."

2011 Cancer System Performance Report-Canadian Partnership Against Cancer



Blogger's Note: 

a specific search of the entire document 'ovary'/'ovarian' found 2 results in the form of references below: 



                                       ~~~~~~~~~~~~~
116.  Du Bois A, Reuss A, Pujade Lauraine E, Harter P, Ray CoquardI, Pfisterer J.

                                             ~~~~~~~~~~~~


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January 30, 2012

Measuring the performance of cancer control to maximize impact
The Partnership releases 2011 Cancer System Performance Report

Measuring the performance of the cancer system provides information that will inform initiatives to optimize quality in cancer control. The Partnership's System Performance Initiative is a collaboration with national and provincial partners to develop a consistent approach to evaluate, compare and identify areas for improvement across Canada's cancer control continuum. As part of this initiative, the Partnership is pleased to release the 2011 Cancer System Performance Report, an annual publication that helps shape this work.

Read more here.


Click here to read or download the 2011 System Performance Report. (pdf automatic download)

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

About the 2011 Report

This 2011 Report is the Partnership’s third report on the performance of the Canadian cancer system. The first two reports were produced in 2009 and 2010. As in the previous reports, this year’s is organized along the
dimensions of the cancer control continuum: Prevention, Screening, Diagnosis, Treatment, Research, Patient Experience (previously Supportive Care and Survivorship), and Long-Term Outcomes. Also bundled with the 2011 Report is Lung Cancer in Canada: A Supplemental System Performance Report.


A chapter titled Developmental and Interim Indicators has been added this year and includes indicators that are still under development and require some additional refinement or validation before they can be included as
performance indicators. This chapter also includes indicators that are not the preferred measures of performance or the specific domain but that are still useful to show until better indicators become available. Interim indicators
are also included because they are used internationally and allow for inter-jurisdictional comparisons.

media: Veterinarians: Pets can help with cancer research



The Associated Press
HOUSTON —
"Leading Texas veterinarians are mobilizing to enlist pets in the testing of experimental cancer therapies, a potential benefit to not just dogs and cats but people.
The veterinarians recently set up a registry they hope will connect pet owners and cancer researchers and show that diseased pets — dogs in particular — are better predictors of the efficacy of new cancer drugs and devices in people than mice, oncologists' favorite test subject historically.
"Dogs may be man's best friend in more ways than one," says Dr. Theresa Fossum, a Texas A&M professor of veterinary surgery and founder of the Texas Veterinary Cancer Registry. "Because they suffer from cancers that are nearly identical to those in humans, but quicker to run their course, they can speed up and make more reliable the process of determining whether a therapy will work."
Veterinarians are just starting to get the ear of cancer researchers......"

"The pet cancer registry is just the beginning. Fossum has plans, once she gets grant money, to launch pet registries for heart and kidney disease too."

press release: High levels of burnout among UK family doctors, especially in group practice



Cancer drugs affect mouse genomes for generations (mice offspring) : Nature News & Comment



"....Furthermore, children who are treated for cancer will not have children of their own for years or decades afterwards. Mice only live about two years, and the ones in Dubrova’s study reproduced a few months after their exposure to the drugs. “I would be very careful in interpreting this data,” Dubrova says."

".....But he (Joe O’Sullivan) also cautions against reading too much into the implications for humans who receive chemotherapy treatments, noting that that the few who do go on to have children are generally asked to wait at least a year after treatment before doing so. “It’s something we’ve generally advised for a long time,” he says, “even though we haven’t had much evidence to back it up.”"

media: Henry Ford 1st in U.S. to Start Trial for Aggressive Brain Tumors - high-grade glioma (HGG)



Patients and referring physicians can call 313-916-8961 for further information.

abstract: Missing content from health-related quality of life instruments: interviews with young adult survivors of childhood cancer



Missing content from health-related quality of life instruments: interviews with young adult survivors of childhood cancer  

Results  
Respondents reported missing, relevant content among all three of the HRQoL instruments. Results identified three content areas of missing information: (1) Perceived sense of self, (2) Relationships, and (3) Parenthood.

Stunning 7-Year Survival Difference in Brain Tumor Trial - oligodendrogliomas (longterm results)



January 30, 2012 — Long-term results from a brain tumor trial show that a chromosomal abnormality — 1p19q codeletion — plays a crucial role in the outcome of patients with oligodendrogliomas. The trial also demonstrates that codeleted tumors are profoundly chemosensitive........

free to view for 7 days: Industry funded clinical trials: bias and quality, Current Medical Research and Opinion, Informa Healthcare



"The quality of the clinical data supporting the development and ultimately the approval for medical use of new drugs is often challenged. Many share the perception that the business goals of the pharmaceutical industry overrule the best scientific efforts to accrue critical knowledge on a new molecule, in order to inform investment of resources, regulatory approvals and appropriate use by patients. Despite this common belief, few scientists have attempted to assess objectively the quality of industry funded (IF) clinical trials by measuring it and comparing it with non-industry funded (NIF) clinical trials in a data-driven fashion. Overall, the average quality of IF clinical research has been reported to be higher than the quality of NIF clinical research."

2012 Publication of Consensus Guidelines on Safety and Quality Indicators in Endoscopy - Canadian Assoc of Gastroenterology



  News Release: January 23, 2012

Publication of Consensus Guidelines on Safety and Quality Indicators in Endoscopy
Media Release (English) (French)
Backgrounder (English) (French)
Consensus Summary
Consensus Paper

When Care Is Worth It, Even if End Is Death - NYTimes.com



"....The idea that we waste money on terminal patients has caught on; the simplicity of the conceit makes it appealing to policy makers. And the data to support it keep coming, because it is easy for researchers to measure how much is spent on patients before they die......"

audio/podcast: ReachMD - Program - Solving the Mystery of Restless Leg Syndrome



Solving the Mystery of Restless Leg Syndrome

Program Description

For the 12 million Americans who suffer from restless leg syndrome (RLS), the disease can often be misdiagnosed and misunderstood. Doctors as well as their patients are now more familiar with RLS due to the intense marketing of drugs used to treat restless legs syndrome. Host Dr. Anthony Alessi talks with Dr. Carl Ansevin, an adjunct faculty member in the department of biomedical sciences at Kent State University and sleep specialist at the Ohio Neurologic Institute in Boardman, Ohio, about how to properly diagnose and treat restless leg syndrome and which patients are more at risk of developing the disease.

Cyberchondria: the one diagnosis patients miss :: Jan. 30, 2012 ... American Medical News



links to article/commentary/blogger's notes: Intravenous Aflibercept for treatment of recurrent symptomatic malignant ascites in patients with advanced ovarian cancer: a phase 2, randomised, double-blind, placebo-controlled study : The Lancet Oncology



Blogger's Note:  reposted from Jan 20th due to Lancet Editorial and reference - paper is open accdess

Intravenous aflibercept for treatment of recurrent symptomatic malignant ascites in patients with advanced ovarian cancer: a phase 2, randomised, double-blind, placebo-controlled study Aflibercept

 Interpretation

This study shows the effectiveness of VEGF blockade in the reduction of malignant ascites, but confirms the significant clinical risk of fatal bowel perforation in this population of patients with very advanced cancer. VEGF blockade should be used with caution in advanced ovarian cancer with abdominal carcinomatosis, and the benefit—risk balance should be thoroughly discussed for each patient.
"In view of the important pathogenetic role of VEGF in ascites formation, the efficacy of VEGF inhibitors have also been assessed in patients with symptomatic malignant ascites. Confirming the results of a recent open-label single-arm phase 2 trial,6 the randomised double-blind placebo-controlled study by Walter Gotlieb and colleagues7 in The Lancet Oncology shows the efficacy of aflibercept in patients with malignant ascites associated with advanced ovarian cancer and can be interpreted as proof of concept. The intervention and the control groups were homogenous, confounding variables controlled, and bias reduced. Therefore, the study has a high internal validity and shows the efficacy of aflibercept. With respect to the clinical implications of the results, symptom relief has to be weighed against discomfort and potentially life-threatening adverse events (three patients had fatal gastrointestinal complications in the aflibercept group vs one in the placebo group), since the treatment is applied to patients in a highly palliative situation. Careful patient selection could reduce the incidence of gastrointestinal perforations. However, before a general recommendation of aflibercept for the treatment of malignant ascites can be made, further studies, including comparative effectiveness research,8 (Blogger's Note: AND patient safety) are needed to compare the effectiveness of the different therapeutic strategies in daily clinical practice."

Sunday, January 29, 2012

open access: Ports and complications for intraperitoneal chemotherapy delivery (ovarian cancer)



"Intraperitoneal access ports are essential to the delivery of chemotherapy agents into the peritoneal cavity of women with ovarian cancer, but their malfunction and adverse effects are frequently responsible for the failure to complete planned therapy. Complications, such as obstruction of the catheter, infection, leakage, rotation, retraction, and pain, together with bowel and vaginal perforation, cause delays in treatment, patient suffering and the expenditure of medical resources. A wide variety of ports have been used, including vascular access devices and intraperitoneal access devices. This paper reviews the development and use of ports for intraperitoneal chemotherapy, their complications and reported methods of prevention...."

(Blogger's Note: tables are included in the text of the paper)

Table 2.   Reported complications of ports used for IP access 
(years 1984 through to 2010)

Table 3.   Percentage of cases where IP chemotherapy was discontinued because of the port 
(years 1994 through to 2010)

Table 4.   Port complications causing the discontinuation of IP chemotherapy* 
(years 1991 through to 2010)

Influence of surgeon and team experience

"There is a lack of information in the literature with regard to the effect of the expertise of the surgeon placing the ports, and the experience of the support team (including doctors and nurses) in managing the ports and patients to reduce complications and improve completion rates...."
Conclusion: 

Port complications are significant, and overall, 15% (210/1945) of patients discontinued IP chemotherapy as a result of a port complication, with obstruction (37.6%) and infection (31.4%) being the most common reasons.

Complications such as leakage, retraction of the catheter, rotation of the portal, difficulties with access and perforation of the bowel can be kept to a minimum with careful technique, but they are still not completely avoidable. Although infection may theoretically be reduced by the avoidance of placement during grossly contaminated surgeries, hard data on the influence of associated bowel surgery at the time of placement are lacking, and there is no proven method of preventing the adhesions that cause obstruction to flow. There does not appear to be a difference in the rates of complications between fenestrated or unfenestrated ports, and the choice of port should be at the surgeon’s discretion.

Despite almost 30 years of experience, it remains difficult to identify which patients are going to experience port complications that impact on the completion of IP therapy. More effective methods of preventing complications and improving tolerability, and thus reducing discontinuation rates, are needed.

open access: The origin of ovarian cancer (including references to familial/non-familial ovarian cancer/inclusion cysts...)



"According to Hamilton,1 the concept that epithelial ovarian cancers arise from ovarian surface epithelial (OSE) cells was proposed by Sir Spencer Wells in 1872. More than a century later, this hypothesis remains controversial....Over the last decade several fundamental observations have documented that epithelial ovarian cancers should no longer be considered as a single disease entity."

Conclusion and future directions

There is recent compelling evidence that histological subtypes of epithelial ovarian cancers represent different disease entities that are characterised by distinct molecular changes. Research into the biology of those cancers, including an investigation of their cell of origin, should therefore be subtype-specific.
The finding by Sharma et al. does not refute the hypothesis of the ovarian origin of epithelial ovarian cancer, but does provoke a discussion about the cellular origin of these cancers. The fallopian tube epithelium is very likely to play an important role in the development of HGSOCs in women with BRCA mutations, and in a subset of non-familial HGSOCs. This does not, however, explain the origin of the majority of sporadic ovarian cancers that may grow directly from the ovary without tubal involvement. It is interesting to note that the data from Sharma et al. show a trend towards an increased risk of epithelial ovarian cancer in women with ICs (inclusion cysts) (relative risk of 1.92), albeit a statistically non-significant increase in risk. It is possible that much smaller ICs may have been missed by pelvic ultrasound, and that those could have contributed to the development of a fraction of epithelial ovarian cancers in the IC-negative women. The evolving model of a tubal origin of ovarian cancer, however, has important implications for future clinical and research directions.
The role of prophylactic salpingectomy alone in reducing the risk of epithelial ovarian cancer should be evaluated only in prospective clinical studies. Novel imaging modalities for the detection of early tubal lesions are needed to investigate the value of early detection of tubal intraepithelial carcinomas in reducing the risk of development of invasive epithelial ovarian cancer.
It is also crucial that further characterisation of the molecular events that control orderly cell division and differentiation of tubal epithelium should be investigated to gain insights into the initiation and progression of pelvic serous cancers.

open access: paper/Editorial - Improvements in survival of gynaecological cancer in the Anglia region of England: are these an effect of centralisation of care and use of multidisciplinary management?



Blogger's Note:  search blog for additional information on centralization of ovarian cancer surgery (eg. Norway...)

 .........................................................
Setting 
In 1999 the DH (Department of Health) in England introduced the Improving Outcomes in Gynaecological Cancer guidance, advising case management by multidisciplinary teams with surgical concentration in specialist hospitals.

In conclusion, there was a highly significant step-change increase in survival in gynaecological cancers associated with the adoption of the 1999 national policy change. ......... These changes have been most marked within endometrial and ovarian cancers.

Editorial: 

"Finally, Crawford and Greenberg on page 160 present their detailed population-based analyses of the effects of centralisation of care on survival outcomes in endometrial and ovarian cancer. Introduced in the UK in the late 1990s, the development of Cancer Networks (the ‘hub and spoke’ model) met with considerable resistance. Although it seemed intuitively right, the evidence to support such health care re-organisations was best described as weak, and they not only needed a significant investment of resources, but also required people to travel away from their immediate locality, making it difficult for friends and families to visit. Now, a number of years on, data are beginning to emerge reassuring all of the interested parties, patients in particular, that the energies and efforts required to implement the principles of centralisation of cancer services appear to have been justified."

open access: Upper abdominal cytoreduction and thoracoscopy for advanced epithelial ovarian cancer: unanswered questions and the impact on treatment - 75 patient study




Positive thoracoscopyNegative thoracoscopy
  1. GOG, Gynecologic Oncology Group.
n (%)27 (36.0)48 (64.0)
Median (range) age, years60.5 (29–75)63 (39–76)
GOG Performance Status (0,1)100%100%
Location of largest disease
Diaphragm2/27 (7.4%)1/48 (2.1%)
Omentum7/27 (25.9%) 10/48 (20.8%)
Pelvis15/27 (55.6%) 37/48 (77.1%)
Lymph nodes2/27 (7.4%)1/48 (2.1%)
Mesentery2/27 (7.4%)1/48 (2.1%)

Table 2.  Surgical Procedures


Table 3.   Morbidity and mortality (Positive/Negative thoracoscopy - complications)

Conclusions

Epithelial ovarian cancer is most commonly diagnosed in advanced stages. The prognostic value of complete cytoreduction has been reported and confirmed in several publications.6,21,22 Similarly intraperitoneal chemotherapy is associated with improved overall survival in women with small-volume residual disease (<1 cm) and, as with cytoreductive surgery, carries with it increased morbidity.

It is therefore mandatory to do all that is necessary to identify disease that cannot be resected before undertaking a maximal cytoreductive effort for disease that will not benefit from the use of intraperitoneal chemotherapy.

Using the surgical approach described allows both of these goals to be met, thereby maximising the potential benefit to women with advanced-stage epithelial ovarian cancer.




open access: Integrated optical coherence tomography, ultrasound and photoacoustic imaging for ovarian tissue characterizationIntegrated optical coherence tomography, ultrasound and photoacoustic imaging for ovarian tissue characterization



"....Detection before the malignancy spreads or at the early stage would greatly improve the survival and benefit patient health. In this report, we present an integrated optical coherence tomography (OCT), ultrasound (US) and photoacoustic imaging (PAI) prototype endoscopy system for ovarian tissue characterization."

"Combining OCT, US and PAI would further provide complementary tissue optical absorption, scattering information, and deep tissue structures. Previously, Yang et al. developed a photoacoustic endoscopy [24]; Yin et al. reported an integrated intravascular OCT and ultrasound imaging probe [25,26]; Wang et al. demonstrated an ultrasound guided spectroscopic intravascular photoacoustic imaging system [27]; Li et al. [28] and Jiao et al. [29] both introduced the integrated OCT and photoacoustic microscopy. For the above referenced studies, either one or two imaging modalities were investigated, although some were not suitable for endoscopy applications. This study, to the best of our knowledge, reports the first prototype system that integrates OCT, US and PAI modalities for endoscopy applications. The performance of the system in ovarian tissue characterization has been demonstrated using ex vivo porcine and human ovaries."

"

Summary

"We have developed the first integrated OCT, US and PAI endoscopy imaging system prototype and explored its application in ovarian tissue characterization. The absorption information provided by PAI, the high-resolution subsurface morphological image provided by OCT and the deeper tissue structures imaged by US demonstrate the great synergy of the combined endoscopy over each modality alone. The initial results have shown that the hybrid device has a potential in ovarian cancer detection and characterization."


repost: what words cannot say.....HOPE and ovarian cancer





media: UNBC Closer To Unique Cancer Drug Research Program - News for Northern/Central Interior British Columbia



"...Dr. Lee says the research will be the first of its kind in Canada - its goal is to develop a method of flagging chemicals that interfere with cancerous activity. Lee has been studying the protein CRD-BP, which is only over-produced in many cancers including: breast, lung, ovarian, colon, and skin cancers. Research at UNBC, and around the world, so far indicates that CRD-BP is associated with cancers because it physically interacts with certain RNA molecules that code for cancer-causing proteins. Dr. Lee and his team hope to find chemical molecules that have the ability to break that interaction....."

abstract: Quality of laparoscopic radical hysterectomy in developing countries: A comparison of surgical and oncologic outcomes between a comprehensive cancer center in the United States and a cancer center in Colombia.



CONCLUSIONS:

Surgical and oncologic outcomes of laparoscopic radical hysterectomy were not worse at a cancer center in a developing country than at a large comprehensive cancer center in the United States. These results support consideration of developing countries for inclusion in collaborations for prospective surgical studies.

website: Lab Tests Online - Understanding Your Tests (American Association for Clinical Chemistry)



subnav top
The site is produced by AACC and is the result of a collaboration of professional societies representing the laboratory community. When we launched this site in 2001, it was a time when health care consumers were being asked to assume more responsibility for their care. Today, knowing more about lab tests and the issues surrounding testing is an important part of fulfilling this responsibility.

abstract: Predictors of prescription errors involving anticancer chemotherapy agents (note: carboplatin)



Blogger's note: stats removed for ease of reading

Aim

The majority of medication errors that harm patients relate to the prescribing process. Our study aimed to identify the predictors of prescription errors involving anticancer chemotherapy agents.

Methods

All consecutive antineoplastic prescriptions from June 2006 to May 2008 were analysed, with medication errors being captured. Potential risk factors for medication prescribing errors were defined in relation to the patient, chemotherapy regimen and hospital organisation. The relationship between these risk factors and observed medication errors or dose medication errors was assessed by univariate and multivariate logistic-regression analyses.

Results

Among the 17,150 chemotherapy prescriptions, 540 contained at least one error (3.15%). The following independent predictors of risk of medication errors were identified: patients with a body surface area , protocols with more than three drugs , protocols involving carboplatin, protocols requiring at least one modification by the physician, inpatient care  and prescriptions by a resident physician. The risk of medication dose prescribing errors was significantly associated with three independent factors: protocols involving carboplatin  protocols with more than three drugs and protocols requiring at least one modification.

Conclusion

In this epidemiologic study, the independent risk factors identified should be targeted for preventive measures in order to improve anticancer agent prescriptions and reduce the risk of medication errors.

Saturday, January 28, 2012

abstract: Survival Benefit Associated With Surgical Oophorectomy in Patients With Colorectal Cancer Metastatic to the Ovary.



Abstract

BACKGROUND AND OBJECTIVES:

The purpose of this study was to determine the outcome of patients with colorectal cancer metastatic to the ovary and the impact of surgical oophorectomy on the outcome.

METHODS:

We conducted a retrospective evaluation of patients with metastatic colorectal cancer to the ovary. Of 3776 female patients with colorectal cancer seen at MD Anderson from 2001-2008, 110 (2.9%) were identified as having metastases to the ovary. The Kaplan-Meier method and log-rank test were used to examine the survival functions.

RESULTS:

Seventy-one patients (64.5%) had disease metastatic to the ovary at the time of initial presentation; in 39 patients (35.5%) the ovaries were a site of relapse after previous curative colorectal surgical resection. Patients who presented with ovarian relapse after previous colorectal surgery and who underwent oophorectomy had a median survival of 50 months compared with 12 months for those who did not (P < .0001). Patients with metastatic disease at the time of presentation who underwent oophorectomy had a median survival of 39.4 months vs. 18.2 months for those who did not.

CONCLUSIONS:

This retrospective analysis suggests that women with metastatic colorectal cancer metastatic to the ovary may derive a survival benefit from palliative oophorectomy.

abstract: Fertility preservation in gynaecological cancer: Epithelial ovarian cancer.



Best Pract Res Clin Obstet Gynaecol. 2012 Jan 24. [Epub ahead of print]

Abstract

The incidence of epithelial ovarian cancer in women aged 40 years and younger is 3-17%. The management of these women is challenging and requires balancing the need to treat epithelial ovarian cancer adequately and preserving reproductive potential. Fertility-sparing surgery, especially for early stage epithelial ovarian cancer, seems to be associated with equivalent clinical and cancer outcomes while preserving reproductive potential. A complete staging and cytoreductive procedure retaining the uterus, and at least one grossly normal ovary, is the minimum recommended procedure. Adjuvant chemotherapy with a platinum-taxane combination is recommended as clinically indicated, and is associated with better cancer and survival outcomes. Adjuvant treatment does not seem to increase the risk of congenital anomalies in subsequent pregnancies. Targeted therapy and ovarian cryopreservation are largely experimental and cannot be recommended as part of the clinical standard of care.

abstract: Chemotherapy and fertility



Best Pract Res Clin Obstet Gynaecol. 2012 Jan 24. [Epub ahead of print]

Abstract

The overall increase in cancer prevalence and the significant increase in long-term survival have generated worldwide interest in preserving fertility in young women exposed to gonadotoxic chemo- and radiotherapy. Infertility represents one of the main long-term consequences of combination chemotherapy given for lymphoma, leukaemia and other malignancies in young women. The gonadotoxic effect of various chemotherapeutic agents is diverse, may involve a variety of pathophysiologic mechanisms, and is not unequivocally understood. Proliferating cells, such as in tissues with high turnover (i.e. bone marrow, gastrointestinal tract and growing ovarian follicles) are more vulnerable to the toxic effect of alkylating agents. These agents may also be cytotoxic to cells at rest, as they are not cell-cycle specific. Alkylating agents, the most gonadotoxic chemotherapeutic medications, cause dose-dependent, direct destruction of oocytes and follicular depletion, and may bring about cortical fibrosis and ovarian blood-vessel damage. The reported rate of premature ovarian failure after various diseases and chemotherapeutic protocols differ enormously, and depend mainly on the chemotherapeutic protocol used and age range of the woman. 

Several options have been proposed for preserving female fertility, despite gonadotoxic chemotherapy: ovarian transposition, cryopreservation of embryos, unfertilised metaphase-II oocytes and ovarian tissue, and administration of gonadotropin-releasing hormone agonistic analogs in an attempt to decrease the gonadotoxic effects of chemotherapy by simulating a prepubertal hormonal milieu.

None of these methods is ideal and none guarantees future fertility in all survivors; therefore, a combination of methods is recommended for maximising women's chances of future fertility.

abstract: Ovarian Cancer Risk Associated with Inherited Inflammation-Related Variants



Abstract

The importance of inflammation pathways to the development of many human cancers prompted us to examine the associations between single-nucleotide polymorphisms (SNPs) in inflammation-related genes and risk of ovarian cancer.
In a multi-site case-control study, we genotyped SNPs in a large panel of inflammatory genes in 930 epithelial ovarian cancer cases and 1,037 controls using a custom array and analyzed by logistic regression. SNPs with p<0.10 were evaluated among 3,143 cases and 2,102 controls from the Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI) collaboration.
Combined analysis revealed association with SNPs rs17561 and rs4848300 in the interleukin gene IL1A which varied by histologic subtype (heterogeneity p=0.03). For example, IL1A rs17561, which correlates with numerous inflammatory phenotypes, was associated with decreased risk of clear cell, mucinous, and endometrioid subtype, but not with the most common serous subtype. Genotype at rs1864414 in the arachidonate 5-lipoxygenase ALOX5 was also associated with decreased risk.
Thus, inherited variation in IL1A and ALOX5 appears to affect ovarian cancer risk which, for IL1A, is limited to rarer subtypes. Given the importance of inflammation in tumorigenesis and growing evidence of subtype-specific features in ovarian cancer, functional investigations will be important to help clarify the importance of inherited variation related to inflammation in ovarian carcinogenesis.

Correspondence: Authors' response: 'Focusing on HER2 as a potential therapeutic target in primary ovarian mucinous carcinomas' (includes stats on serous/endometrioid/clear cell/mucinous)



Blogger's Note: without a subscription ($$$), the following is available for viewing:

Authors' response: 'Focusing on HER2 as a potential therapeutic target in primary ovarian mucinous carcinomas':
In a study involving a large series of epithelial ovarian carcinomas (EOCs), McCaughan et al1 reported human epidermal growth factor receptor 2 (HER2) protein overexpression and amplification in all major histological subtypes, an observation consistent with the literature.2 3 Specifically, they document HER2 gene amplification in 3.0% (7/259) of serous papillary carcinomas, 2.1% (2/92) of endometrioid carcinomas, 25.0% (3/12) of mucinous carcinomas, 4.0% (1/25) of clear cell carcinomas and 11.9% (7/60) of mixed type carcinomas. Although their number of mucinous carcinomas was low (n=12), the higher prevalence of HER2 gene amplification relative to the other histological subtypes is also consistent with the literature.4 5
We had previously reported similar findings of primary ovarian mucinous carcinomas having the highest prevalence of HER2 genomic amplification and protein overexpression among the various EOC histological subtypes and had proposed that ovarian mucinous carcinomas represent a...

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



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

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



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

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

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

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

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

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



CONCLUSIONS:

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

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



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

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

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

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

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

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



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

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



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




The Surprise Question

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

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

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



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

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



Editorial:

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

abstract: original article:

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



Seth's Blog: The honest broker



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



financial news: AstraZeneca cancels Olaparib trial



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