clinical trial: Prospective Research of Outcomes After Salpingo-oophorectomy - BRCA1/2 (PROSper)

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This study is not yet open for participant recruitment.

Verified September 2013 by University of California, San Francisco

Sponsor:

University of California, San Francisco

Collaborator:

American Cancer Society, Inc.

Information provided by (Responsible Party):

University of California, San Francisco

ClinicalTrials.gov Identifier:

NCT01948609

First received: September 12, 2013

Last updated: September 18, 2013

Last verified: September 2013

History of Changes

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  Purpose

PROSper is a prospective cohort study of 100 women 35-50 years of age with BRCA 1/2 mutations who have elected to either undergo risk reducing salpingo-oophorectomy (RRSO) or nonsurgical management. The investigators will compare the change in cardiovascular health, bone health, sexual function, quality of life, and menopausal symptoms over 3 years of follow-up between women who undergo RRSO (baseline just prior to surgery) and age-matched controls that do not undergo RRSO.

The investigators hypothesis is that women who undergo a premature surgical menopause induced by RRSO have worse cardiovascular health and bone health compared with women who do not undergo RRSO.

Condition
BRCA1 Gene Mutation BRCA2 Gene Mutation

 

Study Population

Study participants will be women 35-50 years old with a confirmed diagnosis of a deleterious BRCA 1/2 mutation recruited through UCSF.

Criteria

Inclusion Criteria:

• BRCA mutation 1/2 or "Variant suspected deleterious" mutation.
• Female
• Age 35-50 years
• Able to undergo RRSO
• Speaks English
• Able to give informed consent

Exclusion Criteria:

• Prior history of bilateral oophorectomy
• BRCA 1/2 deleterious mutation
• Plans to move out of geographic region in next 3 years
• Unable to travel to study visits

(U.S.) Expanding HIPAA Rights: Lab Test Results to Come Under the Big Tent | e-Patients.net

e-Patients

"We’re inching closer to promulgation of final regulations that will likely make all lab test results more easily accessible to patients, by making them subject to the HIPAA rules ensuring patient access. (Currently, lab test results and psychiatric notes are the two lone categories of patient data not subject to HIPAA; however “in-house” labs drawn at a health care facility or medical practice are already accessible to patients under HIPAA.) This change is significant in no small part because there was no change in the law that prompted the change in regulation — the only thing that changed was the rising voice of patients insisting on access … and a more receptive set of ears in Washington.... 

Tackling drug-resistant cancers using a genome-forward approach (eg mice and men/women)

medical news

(using breast cancer cells as the example)

"....In other words, the complex human tumor tissues in the mice looked very much like those in the people they originally came from. While some new mutations did arise after transplantation, those genetic changes rarely had functional significance.
The researchers were surprised to discover that the original and PDX cancers were similar at the cellular level as well. Cancer cells carrying mutations that were relatively rare in the patient were also maintained at lower frequencies in the mice. Likewise, more dominant clones in the original tumor tended to stay dominant in the mice. This suggests that the frequency of genetically distinct tumor cells is in an equilibrium that survives transplantation into mice for reasons that aren't yet clear....
 

In Reply: “Double reflection”: A practical approach to teach patient-doctor communication in oncology

In Reply

"....The relevant communication competencies, as listed in the checklist by Mannhardt et al., cover skills related to conveying information in an understandable way and building rapport with patients and others. The differences between and the interdependencies of ethics and communication skills regarding decision making in oncology can be illustrated by item number 8 of the instrument used by Mannhardt et al., on whether goals of the conversation were achieved as viewed by the patient and the doctor [1]. From an ethical perspective, this item begs several questions: whose goals should determine decision making? Were both parties able to make their goals explicit? Was there an exchange of the values underlying the (possibly different) goals? Did they engage in a process of mutual agreement about what the goals of the conversation were?....

References

1. ↵
   1. Mannhardt AK,
   2. Ogbonnaya L,
   3. Gieseler F

   . “Double reflection”: A practical approach to teach patient-doctor communication in oncology [letter]. The Oncologist 2013. (in press).
2. ↵
   1. Schildmann J,
   2. Tan J,
   3. Salloch S,
   4. et al

   . “Well, I think there is great variation.”: A qualitative study of oncologists' experiences and views regarding medical criteria and other factors relevant to treatment decisions in advanced cancer. The Oncologist 2013;18:90-96.

   Abstract/FREE Full Text
3. ↵
   1. Schildmann J,
   2. Kupfer S,
   3. Burchardi N,
   4. et al

   . Teaching and evaluating breaking bad news: A pre-post evaluation study of a teaching intervention for medical students and a comparative analysis of different measurement instruments and raters. Pat Educ Counseling 2012;86:210-214.

   CrossRef
4. ↵
   1. Hope T,
   2. Fulford KW

   . The Oxford Practice Skills Project: Teaching ethics, law and communication skills to clinical medical students. J Med Ethics 1994;20:229-234.

   Abstract/FREE Full Text

 

(U.S.) Health Insurance Marketplace, Affordable Care Act | HealthCare.gov

https://www.healthcare.gov/

A new way to get affordable coverage launches October 1.
Answer a few questions to learn if you qualify for lower costs.

SEE YOUR OPTIONS »

 

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The Consequence of Oncomorphic TP53 Mutations in Ovarian Cancer

Free Full-Text

(This article belongs to the Special Issue Genes and Pathways in the Pathogenesis of Ovarian Cancer)

 

Download PDF Full-Text 

 

Abstract:  

 

Ovarian cancer is the most lethal gynecological malignancy, with an alarmingly poor prognosis attributed to late detection and chemoresistance. Initially, most tumors respond to chemotherapy but eventually relapse due to the development of drug resistance. Currently, there are no biological markers that can be used to predict patient response to chemotherapy. However, it is clear that mutations in the tumor suppressor gene TP53, which occur in 96% of serous ovarian tumors, alter the core molecular pathways involved in drug response. One subtype of TP53 mutations, widely termed gain-of-function (GOF) mutations, surprisingly converts this protein from a tumor suppressor to an oncogene. We term the resulting change an oncomorphism. In this review, we discuss particular TP53 mutations, including known oncomorphic properties of the resulting mutant p53 proteins. For example, several different oncomorphic mutations have been reported, but each mutation acts in a distinct manner and has a different effect on tumor progression and chemoresistance. An understanding of the pathological pathways altered by each mutation is necessary in order to design appropriate drug interventions for patients suffering from this deadly disease.

 

"...One alternative approach is the idea of restoring WT p53 function. The concept of restoring WT
p53 activity is strongly supported by in vitro and in vivo studies as well as several clinical trials
showing that restoration of WT p53 function causes rapid tumor regression in mice and prolonged
survival in humans [101–105]. Various strategies have been employed with the ultimate goal of
restoring WT p53 function. The most common method used to date is gene therapy, namely
introducing a copy of the WT TP53 gene into tumors using an adenovirus. Excitingly, 50% (8 of 16)
women with recurrent ovarian, peritoneal, or fallopian tube cancer that were treated with the
replication-deficient adenovirus encoding human recombinant WT TP53 (SCH 58500) showed a
decrease in serum CA125 levels, indicative of clinical response, with minimal side effects [104].
Moreover, combination of WT TP53 gene therapy with chemotherapeutic drugs such as cisplatin
synergized to enhance clinical efficacy [104]. Unfortunately, an international randomized phase II/III
trial of WT TP53 gene therapy in ovarian cancer was closed after the first interim analysis because
adequate therapeutic benefit was not achieved [105]. A limitation of these studies may have been the presence of an oncomorphic p53 protein that could impose a dominant negative effect on the
therapeutic WT p53 and impede success.
Other approaches such as targeting cellular proteins responsible for stabilizing mutant p53 are
another route that may bring success. A recent development involves inhibiting the heat-shock protein HSP90, which chaperones many mutant p53 proteins [106,107] and prevents their degradation by the E3 ubiquitin ligase MDM2 [108,109]. The interaction between the heat shock protein and its client proteins can be disrupted by acetylation of HSP90, posing an exciting opportunity for the use of HSP90 inhibitors as well as deacetylase inhibitors such as the FDA-approved SAHA (Vorinostat) [110,111].

 

"In summary, the information gained from studying the mutant p53 transcriptome and interactome
described in this review has solidified the foundation for the development of strategies that can one
day be used to treat the large number of cancer patients that harbor TP53 mutations."

 

See One, Do One, Harm One? | The Health Care Blog

See One, Do One, Harm One?

"The team asked why the hospital would perform an operation in which it has little experience. The medical students were especially concerned." 

A Day in the Life of a Patient: Why Can’t We Do Better Than This? | The Health Care Blog

The Health Care Blog

Breast and gynecologic cancer-related extremity lymphedema: a review of diagnostic modalities and management options

 World Journal of Surgical Oncology 2013

Gynecologic oncology perspective on lower extremity lymphedema

The American Cancer Society estimates that there are more than one million gynecologic
cancer survivors currently living in the United States [69]. As this number continues to grow,
more awareness of long-term complications related to the disease and its treatment are
gaining attention. Lower extremity lymphedema (LEL) has been largely understudied and is
one of these unintended consequences. Currently, data on LEL as a result of gynecologic
malignancies has been limited to retrospective studies and has been hindered due to a lack of
standard diagnostic evaluations and assessments, making the diagnosis elusive [70,71].......

Conclusions
The management of lymphedema remains a complex entity that requires knowledge of the
underlying pathophysiology. Patients with breast or gynecologic malignancy are at risk for
the development of lymphedema, particularly in the setting of lymphadenectomy and/or
radiation treatment. Although management with physical therapy remains the primary
treatment, exciting new surgical treatments are under active investigation

Ad Campaigns Compete as Health Law Rollout Looms - NYTimes.com (video - that's disgusting & stupid)

Blogger's Opinion: there is no low point in politics

Ad Campaigns 

"..One group called Generation Opportunity distributed a Web video last week showing a creepy-looking Uncle Sam peering between a woman’s legs at a gynecologist’s office....  

Patient Advocates Briefing for the European Cancer Congress 2013

Patient Advocacy Track

Patient Advocacy & Ethics Track Programme
Saturday 28 to Sunday 29 September 2013

The Patient Advocacy & Ethics Track at the European Cancer Congress, 27 September – 1 October 2013, will focus on the overall theme of ‘Collaboration’ to promote collaboration between health professionals and patients in relevant areas of the cancer patient’s journey to improve cancer outcomes together. It will also include educational topics for patient advocates and opportunities to share and learn from each other’s successful experiences.

The target audience for the Patient Advocacy & Ethics track is both patient advocates and health professionals from all oncology disciplines that attend the Congress. It is not aimed at patients.
Patient advocates are also strongly encouraged to attend scientific sessions and the Oncopolicy Forum.

• Read or download the Patient Advocates Briefing (PDF)
• See the full Patient Advocacy and Ethics Track (click Track drop-down and select only "Patient Advocacy/Ethics" and then SEARCH)

 

Abstract Search - European Cancer Congress 2013

Abstract Search (ovarian cancer results)



 

Quantification of harms in cancer screening trials: literature review | BMJ

open access

Results Out of 4590 articles assessed, 198 (57 trials, 10 screening technologies) matched the inclusion criteria. False positive findings were quantified in two of 57 trials (4%, 95% confidence interval 0% to 12%), overdiagnosis in four (7%, 2% to 18%), negative psychosocial consequences in five (9%, 3% to 20%), somatic complications in 11 (19%, 10% to 32%), use of invasive follow-up procedures in 27 (47%, 34% to 61%), all cause mortality in 34 (60%, 46% to 72%), and withdrawals because of adverse effects in one trial (2%, 0% to 11%). The median percentage of space in the results section that reported harms was 12% (interquartile range 2-19%).

Conclusions Cancer screening trials seldom quantify the harms of screening. Of the 57 cancer screening trials examined, the most important harms of screening—overdiagnosis and false positive findings—were quantified in only 7% and 4%, respectively.

Introduction

Cancer screening can lead to harm as well as benefit.1 2 3 Harm related to screening can be somatic or psychosocial.4 5 6 7 8 9 10 11 12 13 Harms result from the screening test itself, from investigations because of false positive findings, and from overdiagnosis with subsequent overtreatment.3 5 12 13 Given the potential for serious harms in healthy individuals, screening should be offered only when the benefits are firmly documented and considered to outweigh the harms, which should be equally well quantified. The determination of benefit from screening requires assessment in randomised clinical trials, which are also capable of providing high quality evidence on harms.14 15 In general, however, harms are poorly reported in randomised trials,16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 and there is some evidence that reporting of harms is worse in non-pharmacological trials than in trials assessing drugs.22 23 24

At least three additional arguments support the importance of reporting harms in randomised trials of cancer screening. Firstly, screening is offered to healthy individuals and is an intervention initiated by the healthcare system, not at the request from a patient to solve a health problem. Secondly, interventions for which the benefits are modest or uncertain merit detailed consideration of harms,32 and systematic reviews of randomised trials of screening have shown either modest33 34 35 or no36 reductions in cancer specific mortality. Thirdly, a benefit for some will come at the expense of harm to others.37 38 39

The minimum evidence required to assess the harms of screening includes the frequencies of false positive findings, overdiagnosis, and complications of diagnostic investigations and treatment.13 In addition, withdrawals because of harms19 and the use of invasive follow-up procedures can be considered as proxy measures of severe harms. We hypothesised that cancer screening trials would not consistently or sufficiently quantify the expected associated harms.

Methods

Eligibility criteria

We included trials that evaluated breast cancer screening with mammography, self examination, or clinical examination; colorectal cancer screening with sigmoidoscopy or colonoscopy, faecal occult blood testing, or virtual colonoscopy; liver cancer screening with ultrasonography, α fetoprotein, or a combination; lung cancer screening with chest radiography or low dose spiral computed tomography of chest; ovarian cancer screening with ultrasonography, serological markers, or a combination; oral cancer screening with visual inspection; prostate cancer screening with prostate specific antigen, digital rectal examination, or a combination; and testicular cancer screening with self examination or clinical examination.

Publications reporting randomised trials were eligible if the trial compared a group of participants undergoing a cancer screening intervention with either no screening or an alternative screening intervention....


 

Consumers' voices - Cochrane Collaboration

BRCA1 homepage - LOVD - Leiden Open Variation Database - Leiden Open Variation Database

BRCA1

Last update August 27, 2013

This database has just been initiated and we are still considering changes to improve its functionality. 

MSH2 homepage - Colon cancer gene variant databases - Leiden Open Variation Database (searchable)

Blogger's Note:  using MSH2 as an example; click on either the MSH2 or 'switch gene' eg. search will bring up related genes such as PMS2/MLH1

MSH2 homepage

Switch gene

MSH2

Last update September 18, 2013

NOTE: in this database entries from the MMR, InSiGHT and MMRUV databases (for links see the gene homepage) have been merged. In addition new, unpublished variants have been entered by submitters directly. 

Update of variant in MSH2 gene database - MSH2:c.1277-4076_1386+1819del6005; reported as pathogenic

April 19 2013 7:01 AM

Update of variant in MSH2 gene database - MSH2:c.1277-6224_1386+4836del11170; reported as pathogenic

April 19 2013 6:55 AM

Update of variant in MSH2 gene database - MSH2:c.1277-6284_1386+4776del11170; reported as pathogenic

April 19 2013 6:47 AM

Update of variant in MSH2 gene database - MSH2:c.1276+198_1386+3761del19280; reported as pathogenic

April 19 2013 6:37 AM

The role of surgery in the management of patients with platinum-sensitive recurrent ovarian cancer: Survey among Dutch gynecologists and medical oncologists

abstract

---

Highlights

•

We carried out a survey to assess current opinions of Dutch gynecologists and medical oncologists regarding surgery in recurrent ovarian cancer

•

Most respondents were convinced of the benefit of secondary cytoreductive surgery and shared their opinion regarding diagnostic and therapeutic aspects

•

Gynecologists and medical oncologists differed in their opinion regarding the gain in both progression free as well as overall survival

---

Objective

Evidence of randomized comparative clinical trials on surgery in recurrent platinum-sensitive ovarian cancer is non-existing. Three randomized phase 3 trials are ongoing. The aim of this study is to evaluate the current opinion of Dutch gynecologists and medical oncologists awaiting the results of these three trials.

Methods

A 16-item questionnaire was sent to all gynecologists (N = 124) and medical oncologists (N = 195) with special interest in gynecologic oncology in the Netherlands. The data were collected and analyzed using descriptive statistics.

Results

In total, 80 (65.0%) gynecologists and 67 (34.0%) medical oncologists responded. Among the respondents, 11.3% and 26.9% were not convinced of the benefit of secondary cytoreductive surgery, respectively. For most gynecologists and medical oncologists completeness of primary surgery (74.6% and 75.5%, respectively) and performance status (100% and 98%, respectively) were important factors when considering surgery. For only about 17.5% of all respondents diagnostic laparoscopy before surgery is a prerequisite. Most respondents (81.7% and 87.8%, respectively) would use platinum-based chemotherapy with paclitaxel as their agents of choice after surgery. In general medical oncologists settle for a smaller gain in both progression free as well as overall survival than gynecologists.

Conclusions

Although most gynecologists and medical oncologists are already convinced of the usefulness of secondary cytoreductive surgery in certain patients, a better understanding of the real advantages and disadvantages and patient’s selection criteria for secondary cytoreductive surgery will be achieved after the completion of three ongoing randomized controlled trials (DESKTOP III, GOG 213 and the SOCceR).

Purchase $39.95

 

Evaluation of the cost of CA-125 measurement, physical exam, and imaging in the diagnosis of recurrent ovarian cancer

abstract

---

Highlights

•

Ovarian cancer patients are followed with National Comprehensive Cancer Network Guidelines

•

95% of patients with recurrence had findings at time of office visit or elevated CA 125

•

Imaging for post treatment screening increased cost with little increase in recurrence detection

---

Objective

Ovarian cancer accounts for 50% of deaths from gynecologic malignancies. We sought to determine the cost of common methods of surveillance of women with ovarian cancer in first clinical remission. The current standard for post treatment surveillance is the National Comprehensive Cancer Network (NCCN) guidelines.

Methods

We retrospectively determined how recurrence was initially detected at our institution and a cost model was created and applied to the United States population to calculate surveillance costs using the Surveillance Epidemiology & End Results (SEER) database.

Results

57% (n = 60) of first recurrences were identified by increasing CA 125 level. Routine office visit identified 27% (n = 29) of recurrences, and 15% (n = 16) were diagnosed initially with CT scan. In 5% (5/105), CT abnormality was the only finding. 95% (100/105) of patients had either elevated CA 125 or office visit findings at time of recurrence. Of the 22,000 women diagnosed with ovarian cancer yearly, 60% (n = 13,266) will have advanced disease and are likely to recur. The surveillance cost for this population for 2 years using our model is $32,500,000 using NCCN guidelines and $58,000,000 if one CT scan is obtained.

Conclusions

Our data suggests that following NCCN guidelines will detect 95% of recurrences. An additional $26 million will be needed to identify the 5% of women with recurrence seen on CT only. Post treatment surveillance of ovarian cancer patients contributes significantly to health care costs. Use of CT scan to follow these patients largely increases cost with only a small increase in recurrence detection.

Purchase $39.95

 

Dangerous Digs - A cell's surroundings may be instrumental to the development of cancer | Genes & Cells | Science News

Science News

".... On average, about 8 of every 100 women will develop breast cancer by age 70. But 50 to 70 of every 100 women with BRCA1 mutations will get the disease before age 70, and usually at much younger ages.
Bissell sees a different story in those numbers. She points to all the women with a BRCA1 mutation who never develop cancer. Plus, she adds, the gene is instrumental for helping repair damaged DNA in every cell of the body. Yet most carriers of the faulty gene develop either breast or ovarian tumors. “So why don’t you get pancreatic cancer or brain cancer?” Bissell asks. For that matter, “why doesn’t the entire breast or the entire body turn into a tumor?”.....
 

Progress in Survival Outcomes in Patients with Advanced Ovarian Cancer Treated by Neo-Adjuvant Platinum/Taxane-Based Chemotherapy and Late Interval Debulking Surgery

abstract

BACKGROUND:

Steady progress in outcomes has been observed after standard treatment by surgery and chemotherapy in patients with advanced ovarian cancer (AOC), but little is known about outcomes after alternative neoadjuvant chemotherapy (NAC) proposed to primary inoperable patients. We assessed whether NAC offers comparable survival to standard treatment, whether survival rates have progressed over time, and what the optimal extent of surgery at late interval debulking surgery (IDS) should be.

METHODS:

This was a retrospective data analysis of prospectively recorded patients with poor prognosis AOC treated by platinum/taxane NAC and late IDS (after six cycles). Independent prognostic factors for surgical morbidity and overall survival (OS) are determined and survival outcomes are compared to survival rates for a similar group of patients treated with platinum protocols.

RESULTS:

A total of 118 patients with stages IIIC-IV AOC (median age: 64 years, stage IV: 31 %) received IDS (46 % standard surgery and 54 % radical, with 68 % obtaining complete resection). Major morbidity was 18 %. OS was 42 months across all patients (95 % confidence interval 35.3-49.1) and 80 months in stage IIIC. This is higher by 15 months than after platinum-based treatment. Higher morbidity was associated with bowel resection. Longer OS was associated with ASA class I, stage IIIC, no bowel surgery, and no residual disease.

CONCLUSIONS:

The neoadjuvant approach with late IDS offers survival similar to that reported by standard treatment, with progress in outcomes compared with rates after platinum treatment. The goal of IDS surgery is complete resection, while sparing surrounding organs.

 

Genetic variation of the brca1 and brca2 genes in macedonian patients

Gabstract

The most significant and well characterized genetic risk factors for breast and/or ovarian cancer are germline mutations in the BRCA1 and BRCA2 genes. The BRCA1 and BRCA2 gene mutations strikingly increase breast cancer risk, suggesting that polymorphisms in these genes are logical candidates in seeking to identify low penetrance susceptibility alleles. The aim of this study was to initiate a screen for BRCA1/2 gene mutations in order to identify the genetic variants in the Republic of Macedonia, and to evaluate the association of several single nucleotide polymorphisms (SNPs) in these genes with breast cancer risk. In this study, we included 100 patients with invasive breast cancer from the Republic of Macedonia, classified according to their family history and 100 controls. The methodology included direct sequencing, single nucleotide primer extension method and multiplex ligation probe amplification (MLPA) analysis, all followed by capillary electrophoresis (CE) on an ABI PRISM™ 3130 Genetic Analyzer. We identified a total of seven carriers of mutations in the BRCA1/2 genes. None of the tested polymorphisms was associated with sporadic breast cancer risk, however, polymorphism rs8176267 in BRCA1 and N372H in BRCA2 showed an association with breast cancer risk in patients with at least one family member with breast cancer.

 

Supplemental screening ultrasound increases cancer detection yield in BRCA1 and BRCA2 mutation carriers

Abstract

INTRODUCTION:

This study aimed at evaluating the efficacy of ultrasound for the early detection of breast cancers in BRCA1/2 mutation carriers.

METHODS:

Between 01/1997 and 10/2008 221 BRCA1/2 mutation carriers participated in a breast cancer screening program which included semi-annual ultrasound in combination with annual mammography and magnetic resonance imaging (MRI). Women underwent on average (median) five semi-annual screening rounds with a range of one to 22 appointments, totaling 1,855 rounds of screening. All three imaging modalities were coded according to the American College of Radiology (BI-RADS classification).

RESULTS:

In total, we detected 27 BRCA-associated breast cancers in 25 patients. The sensitivity was 77 % for ultrasound, 27 % for mammography, and 100 % for MRI. Three tumors were detected directly as a result of only the semi-annual ultrasound screen.

CONCLUSIONS:

Due to the specific tumor morphology and the considerably elevated tumor doubling time, mutation carriers benefit from the addition of semi-annual ultrasound screening as a sensitive and cost-effective method.

 

Darlene GRAY Obituary

Darlene GRAY

GRAY, Darlene Ann
July 22, 1957 – September 17, 2013


Darlene Ann Gray passed away on September 22, 2013 at Grace Hospice at the age of 56 after a long and courageous battle with cancer. She was born on July 22, 1957 in Regina, the middle daughter of Ida and Maynard Gray. Darlene was predeceased by her mother Ida in 1993. She is survived by her husband Alvin Huber, companion little Guido, Father Maynard Gray, sisters Dorothy (Ross) Beal, Donna Lee (Emmet) Boyle, brothers Don Gray, David (Pam) Gray, Mother–in-Law Orpha Huber, brothers-in-law Glen Huber, Randy (Donna Frank) Huber, numerous nieces, nephews, in-laws and friends. Darlene spent many years in the Human Resources field, employed at various companies and later with her own consulting business. She was very proud of her Diploma in Adult Education she received from St Francis Xavier University in 2002, and her Canadian Human Resources Professional (CHRP) certification. After moving to Whitehorse in 2003 Darlene found her true passion in painting and pursued that passion through acrylic painting and photography until she could no longer do either. After contracting Ovarian Cancer in 2007 Darlene also put her passion into Ovarian Cancer treatment and support for women diagnosed with Gynecological Cancers. Her never ending commitment to providing better support and treatment often put her at odds with administrators, government officials and other cancer organizations. Only the diagnosis of Brain Cancer stopped her from continuing with this passion. Darlene found great comfort in her weekly meditation circle where she shared her own wisdom and compassion with great joy. Darlene continues her compassion for people even through death by donating her body to the University of Saskatchewan, College of Medicine for research and study. The family would like to extend their gratitude to all the Doctors, Nurses and staff at the Regina Cancer Clinic, Palliative Care Unit, Regina Wascana Grace Hospice, the Community Clinic and all the friends and family who supported us through Darlene's journey. In lieu of flowers memorial donations in memory of Darlene can be made to the Regina Community Clinic, the Pasqua Palliative Care Unit, or a charity of your choice. A celebration of Darlene's life will be held on September 28, 2:00 PM at the Sunset United Church, 177 Sunset Dr. Regina.

Lynch Syndrome: A Pediatric Perspective

abstract

Colorectal cancer is a rare disease in the pediatric age group and when present suggests an underlying genetic predisposition. The most common hereditary colon cancer susceptibility condition, Lynch syndrome, previously known as Hereditary Non-Polyposis Colorectal Cancer is an autosomal dominant condition caused by a germline mutation in one of four DNA mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. The mutation prone phenotype of this disorder is associated with gastrointestinal, endometrial and other cancers and is now being identified in both symptomatic adolescents with malignancy as well in asymptomatic mutation carriers who are at risk for a spectrum of gastrointestinal and other cancers later in life. We review the DNA mismatch repair system, our current understanding of Lynch Syndrome in the pediatric population and discuss the newly identified bi-allelic form of the disease known as Constitutional Mismatch Repair Deficiency Syndrome.

Both family history and tumor characteristics can help to identify patients who should undergo genetic testing for these cancer predisposition syndromes. Patients who carry either single allele (Lynch Syndrome) or double allele (Constitutional Mismatch Repair Deficiency Syndrome) mutations in the mismatch repair genes benefit from cancer surveillance programs that target both the digestive and extra-intestinal cancer risk of these diseases. Since spontaneous mutation in any one of the mismatch repair genes is extremely rare, genetic counseling and testing is suggested for all at-risk family members.

 

Impact of cardiovascular comorbidity on ovarian cancer mortality

Abstract

Background:

A retrospective cohort study utilizing prospectively collected data was conducted from August 2003 until March 2008 at M. D. Anderson Cancer Center. It is unknown whether cardiovascular comorbidity and chronic stress impact ovarian cancer outcome, which remains poor despite advances in therapy. The purpose of this study was to determine whether cardiovascular disease and markers that may be associated with stress are also associated with survival in ovarian cancer patients.  

Methods:

Participants with newly diagnosed epithelial ovarian cancer were followed until time of death or truncation of study period (median follow-up = 4.2 years; n=271). Tumor characteristics (stage, tumor grade, histology, debulking status), demographic variables,and cardiovascular comorbidity were documented and compared to overall survival. 

Results:

Of the 9 cardiovascular events tracked during follow-up, venous thromboembolism (VTE; Hazard Ratio= 3.2; 95%CI = 1.8-5.5) and pulmonary hypertension (Hazard Ratio=8.5; 95%CI= 3.9- 18.7) were associated with shorter survival in multivariate analysis. In addition, high tumor grade, suboptimal cytoreduction, and baseline heart rate (Hazard Ratio=1.02; 95%CI= 1.01- 1.04) were related to decreased survival. 

Conclusions:

Careful management of certain cardiovascular comorbidities may extend survival in patients with ovarian cancer. Our findings suggest that increased baseline heart rate and the development of VTE and pulmonary hypertension after cancer diagnosis may be significant predictors of survival in women with ovarian cancer. Impact: Our study emphasizes the importance of identifying and optimally treating tachycardia, VTE and pulmonary hypertension in conjunction with cancer therapy.

 

website: Applied Integrin Sciences - Integrins

Home Page

Applied Integrin Sciences' drug candidate eliminates ovarian cancer tumors in pre-clinical study - medical news ( Vicrostatin and ADM-01)

medical news

  Published on September 21, 2013

Applied Integrin Sciences, Inc. announced today that its first cancer therapeutic drug candidate eliminated all intraperitoneal ovarian cancer tumors in a pre-clinical study testing a novel treatment regimen. Funded by the National Cancer Institute through the company's first NCI grant awarded December last year, its lead candidate drug Vicrostatin was combined with a drug-eluting gel and applied into the peritoneum for sustained release of the drug directly to ovarian cancer metastatic tumors. 
"The results our scientists achieved are exceptional", said Thomas C. Chen, MD, Ph.D., the company's Chief Medical Officer, "and suggest an equivalent human treatment for ovarian cancer patients is feasible.  The implications for this treatment are equally compelling as 75% of women first diagnosed with ovarian cancer have stage III or stage IV metastatic disease and 80% of those women fail to survive longer than 20 months post diagnosis. This approach is early but if we are able to achieve comparable results in human clinical trials with women suffering from ovarian cancer this treatment could considerably change the current standard of care.".....

 

The role played by the microenvironment in site-specific metastasis

abstract


"Cancer cells that disseminate to metastatic sites may progress to frank metastasis or persist as dormant micrometastasis. Significant progress has been made in defining the genetic and phenotypic cancer-cell-autonomous determinants of metastasis and in the understanding of the cross-talk between metastasizing tumor cells and the metastatic microenvironment.
However several questions remain open, in particular the identity of microenvironmental factors that keep micrometastatic cells in a state of dormancy and those that promote survival, proliferation and progression of such cells. Significantly more information is available on the latter factors than on microenvironmental cells and molecules that restrain micrometastasis. This mini-review summarizes findings suggesting that:

•The interactions between the metastatic microenvironment and cancer cells metastasizing to this microenvironment are unique to each metastatic microenvironment.

•cells or molecules in the metastatic microenvironment could act as "double agents" exerting pro- or anti-malignant functions.

•In the early phases of tumor progression, the interactions between cancer cells and the metastatic microenvironment are inhibitory whereas in later stages such interactions promote progression towards metastasis.

In view of the above, it is not unlikely that metastases residing in different microenvironments may require “individualized” treatment modalities."
 

Pause to reflect on excellence in health/medical science reporting

Healthnewsreview

Reforming Canadian Primary Care – Don't Stop Half-Way :: Longwoods.com

 Blogger's Note: references Commonwealth Fund data and other countries as comparisons; some excerpts:

open access

 ......"Unfinished Business
The medicare we have today is not the entire program envisioned by Tommy Douglas and Emmett Hall. In 1961, Douglas said: "This [the proposed Saskatchewan Medical Care Insurance plan] … will prove to be the forerunner of a national medical care insurance plan. It will become the nucleus around which Canada will ultimately build a comprehensive health insurance program which will cover all health services – not just hospitalization and medical care – but eventually … all other services which people receive." Featured prominently in the Hall Commission Report (Royal Commission 1964) was a "Health Charter for Canadians" calling for a comprehensive, universal health service program "including] all health services, preventive, diagnostic, curative and rehabilitative, that modern medical and other sciences can provide." The Commission made specific recommendations for coverage of vision care, dental care and pharmaceuticals. This vision has yet to be realized.
Nevertheless, Professor Ted Marmor at Yale University has referred to Canadian medicare as a public policy miracle. Perhaps what is truly miraculous is that in an inherently unequal capitalist society, where access to almost all other goods and services depends on ability to pay, the majority of Canadians supported, and continue to support, a program that rests on the fundamental principle that access to care should be determined solely by medical need....But if the principle of care based on need deserves our support in relation to hospital and physicians' services, why should it stop there? What about other beneficial health services such as pharmaceuticals, vision care, dental care, home care, chiropractic services and rehabilitation therapies? We have few principled answers."

"We Can't Afford" Medicare – New Singers, Same Old Song

The plea for continuing investment in primary care – or, indeed, any other health sector – is frequently countered by concerns about the rising share of health spending in provincial government budgets, and more generally about rising total public and private health expenditures as a proportion of gross domestic product (GDP). Often the two are lumped together as a concern about medicare's alleged "unsustainability," though the linkage is faulty and confused (or deliberately deceptive). Those who allege unsustainability are in fact arguing for an expanded role for private financing, user payment with or without private insurance....

"The relationship between values and income means that the struggle to maintain, improve and expand medicare as a program that embodies the core value articulated by Douglas and Hall – healthcare access and quality based solely on need – will continue to face opposition from individuals and organizations whose economic and political influence is disproportionate to their numbers. However, the line-up today is essentially the same as it was when medicare was being debated in the 1960s. We won then, and we can win again."

Secretory cell expansion with aging: Risk for pelvic serous carcinogenesis

  Open Access

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Highlights

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Increased number of tubal secretory cells (secretory cell expansion, SCE) is closely associated with age.

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SCE is more prevalent in both fimbria and ampulla tubal segments and is significantly associated with serous neoplasia.

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Age remains an independent risk factor for pelvic serous carcinoma.

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Abstract

Objective

Recent advances suggest that precancerous lesions of pelvic serous carcinoma (PSC) originate from tubal secretory cells. The purpose of our study was to determine if increased number of secretory cells shows difference in age and location and to examine their association with serous neoplasia.

Materials and methods

Three groups (benign control, high-risk, and PSC) of patients with matched ages were studied. The age data was stratified into 10-year intervals ranging from age 20 to older than 80. The number of secretory and ciliated cells from both tubal fimbria and ampulla segments was counted by microscopy and immunohistochemical staining methods. The data was analyzed by standard contingency table and Poisson distribution methods after age justification.

Results

We found that the absolute number of tubal secretory cells increased significantly with age within each age group. Age remained a significant risk factor for serous neoplasia after age adjustment. In addition, a dramatic increase of secretory cells was observed in high-risk and PSC patients. Further, secretory cell expansion (SCE) was more prevalent than secretory cell outgrowth in both fimbria and ampulla tubal segments and was significantly associated with serous neoplasia (p < 0.001).

Conclusions

These findings suggest that SCE could potentially serve as a sensitive biomarker for early serous carcinogenesis within the fallopian tube. Findings support a relationship between serous neoplasia and increased secretory to ciliated cell ratios. Findings also support a relationship between frequency of SCE and increasing age, presence of high-risk factors and co-existing serous cancers.

" Case collection
A total of 312 consecutively identified cases of the fallopian tubes, all surgically
removed from 2007 to 2012 were culled from pathology files of University of Arizona
Medical Center in Tucson, Arizona.....

 

Examination of the taste disorder associated with gynecological cancer chemotherapy

abstract

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Highlights

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Gustatory tests were performed to clarify taste disorders during chemotherapy.

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Tests were trace element, tongue culture, electrogustometry, and filter paper disc.

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Abnormal test results were seen in half of the patients after cancer chemotherapy.

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Objective

Taste disturbance is known to occur as one of the adverse events associated with chemotherapy for gynecological cancer, but few studies have attempted to assess it in practical terms. Therefore, a range of taste tests was performed in gynecological cancer patients.

Methods

The patients were 23 women with gynecological cancer being treated with anticancer agents. Subjective symptoms of altered taste were classified, and objective findings were obtained with the following four gustatory tests: serum trace element (zinc, copper, iron) levels, tongue cultures, electrogustometry, and the filter paper disc tests.

Results

Of the 23 subjects, 11 perceived taste disturbances. The serum zinc level was consistently below the lower limit of normal. On tongue cultures, indigenous bacteria were seen in all patients during the entire treatment period. Electrogustometry revealed a tendency for the development of hypogeusia in the chorda tympani nerve field. Conversely, hypergeusia tended to develop gradually in the greater petrosal nerve field. The filter paper disc test revealed a tendency for the development of hypergeusia for sweetness, saltiness, and sourness in the chorda tympani nerve field. Hypogeusia for bitterness tended to develop with increasing number of chemotherapy cycles. The glossopharyngeal nerve field exhibited the same tendencies as observed in the chorda tympani nerve field. In the greater petrosal nerve field, there was a tendency for the development of hypergeusia for sweetness, sourness, and bitterness.

Conclusions

Abnormal test results were seen in half of patients after cancer chemotherapy.

Purchase $39.95

 

The Impact Of Germline Mutations On Targeted Therapy

abstract

Invited review

The Journal of Pathology

"Targeted therapies provide clinical benefit and improved therapeutic index. They have a growing prominence in patient management and focus in drug development. Their development is fuelled by our deepening knowledge of complex disease phenotypes and the need for improvement in new therapeutic efficacy. Extrapolation of the biological discovery through to new therapy targeting the causal biological variants to drive clinical gain is challenging. Here, we review the impact of germline mutations on targeted therapies. Historically, germline changes have contributed most to our understanding of disease mechanisms, and drug metabolism and exposure, the latter of which has enabled safer positioning of therapies, such as clopidogrel and irinotecan. Similarly, pre-screening for germline variants can avoid potentially fatal hypersensitivity reactions with abacavir. However, germline mutations continue to emerge as a central player in targeting therapeutics; ivacaftor drives partial restoration of mucus secretion in cystic fibrosis patients harbouring specific mutations and treatment with olaparib exploits germline mutations in BRCA genes to drive synthetic lethality as an anti-cancer mechanism. Central is definition of the causal link, association or contribution to the biological variance – and that we believe it is drugable for therapeutic gain. The demand for better therapies to treat modern diseases provides the appetite for continued investigation of the biologic variance associated with germline mutation, inevitably leading to increased impact on development of targeted therapeutics."

Systematic Reviews | Abstract | Helping people make well-informed decisions about health care: old and new challenges to achieving the aim of the Cochrane Collaboration

open access Cochrane Collaboration

The aim of the Cochrane Collaboration is to help people make well-informed decisions about health care by preparing, maintaining and promoting the accessibility of systematic reviews of the effects of health care interventions. This aim is as relevant now as it was 20 years ago, when the Cochrane Collaboration was established. Substantial progress has been made toward addressing challenges to achieving the Collaboration's aim. At the same time, a huge amount of work remains to be done. Current challenges include improving the quality of reviews, methodological challenges, meeting the needs of contributors and users and taking on new challenges while staying focused on the Collaboration's aim. Radical thinking and substantial change may be needed to identify and implement pragmatic strategies to ensure that reviews are up-to-date and informative. Methodological challenges include the development and application of better methods for addressing explanatory factors, incorporating non-randomized evidence and making comparisons across multiple interventions. Innovations in editorial processes and strategies to meet the needs of low- and middle-income countries and diverse users of Cochrane reviews are needed. Finally, although it is important to consider broadening the aims of the Collaboration to include types of questions other than the effects of interventions and types of products other than the Cochrane Library, we should not lose sight of the aim of the Cochrane Collaboration. Addressing that aim is still a major challenge that requires the collaboration of thousands of people around the world and continuing improvements in the methods used to achieve that aim.

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

 "Background
At the turn of the 21st century, I described 10 major challenges to achieving the Cochrane
Collaboration’s aim [1,2]. Herein I consider progress in addressing those challenges and a
new set of challenges. The need to address these challenges (by the Cochrane Collaboration or by others) remains the same; that is, that the alternative––poorly informed decisions––is not acceptable.......

 

(transdermal patch) Hormone replacement therapy formulations may cause different risks for stroke, heart attack

medical news

"...The WHI trials examined only synthetically-derived hormones delivered in pill form... 

NCI Cooperative Clinical Trials Groups proceed with reorganization

reorganization

 

A*STAR Scientists Find a Promising Way To Boost The Body’s Immune Surveillance Via p53, “The Genome Guardian” In The Fight Against Cancer

Press Release

Exploring the benefits of the Mediterranean diet: evidence from the PREDIMED trial - BioMed Central blog

open access - blog

PHD Comics - Google+ (a little humour today)

Blogger's Note: can be found on FB, Google+, Twitter etc

PHD Comics - Google+

website

Darlene Gray

From Bench to Bedside: Does Preclinical Practice in Translational Oncology Need Some Rebuilding?

Abstract

"After years of enormous research efforts for the systematic cataloguing of genetic alterations with causative function in cancer, the goal of “personalized medicine” in clinical oncology is now potentially in reach (1). With the overall aim to characterize more than 25,000 genomes from the 50 more relevant cancer types, major international endeavors are ongoing to provide a complete inventory of oncogenic mutations (2). When combined with the massive capacity of modern pharmaceutical companies to screen for inhibitors that target “druggable” mutant gene products, this undertaking will offer unprecedented opportunities to treat cancer through “precision” approaches whereby therapeutic decisions are informed by the genomic makeup of each tumor in each patient.

Nevertheless, the ultimate clinical implementation of personalized medicine in oncology is still a major challenge. Indeed, the categorization of molecularly circumscribed tumor subpopulations featuring specific genetic lesions, the validation of such lesions as therapeutic targets, and the definition of biomarkers for accurate prediction of sensitivity to rational treatments face technical, logistic, and ethical limitations in patients. If cancer therapies must be tailored around small, genetically defined patient subgroups, the efforts essential to identify, recruit, and treat a number of patients great enough to validate the therapeutic relevance of new targets must be massive and may hardly justify high-risk drug development strategies. Highly reliable preclinical models for discrimination between “actionable” therapeutic opportunities and those with weak clinical transferability are thus urgently needed to improve the bench-to-bedside … 

[Full Text of this Article] (requires paid subscription)

 

Charity calls for routine BRCA testing of ovarian cancer patients | BMJ (England)

 BMJ

All women in England with ovarian cancer should be tested for the BRCA1 and BRCA2 mutations at the time of diagnosis, as currently happens in Scotland, a charity has demanded.

The call by Ovarian Cancer Action was backed by an expert panel of geneticists, genetic counsellors, and medical oncologists at a panel discussion held last week at the Royal Society in London.

The charity’s policy paper calls for all women with invasive non-mucinous epithelial ovarian cancer, …

 

Acute myeloid leukemia - Wikipedia, the free encyclopedia

open access Wikipedia, the free encyclopedia

Epidemiology

Acute myeloid leukemia is a relatively rare cancer. There are approximately 10,500 new cases each year in the United States, and the incidence rate has remained stable from 1995 through 2005. AML accounts for 1.2% of all cancer deaths in the United States.^[1]
The incidence of AML increases with age; the median age at diagnosis is 63 years. AML accounts for about 90% of all acute leukemias in adults, but is rare in children.^[1] The rate of therapy-related AML (that is, AML caused by previous chemotherapy) is rising; therapy-related disease currently accounts for about 10–20% of all cases of AML.^[72] AML is slightly more common in men, with a male-to-female ratio of 1.3:1.^[73]
There is some geographic variation in the incidence of AML. In adults, the highest rates are seen in North America, Europe, and Oceania, while adult AML is rarer in Asia and Latin America.^[74][75] In contrast, childhood AML is less common in North America and India than in other parts of Asia.^[76] These differences may be due to population genetics, environmental factors, or a combination of the two.....
 

Tracking Chemotherapy’s Effects on Secondary Cancers

 Blogger's Note: the fact that secondary cancers arise from chemotherapy treatments is not new; search blog/medline etc for "treatment related second primary cancers" (or similar phrase)

abstract

"Certain chemotherapies, including anthracyclines for breast cancer and topoisomerase inhibitors for leukemia, raise the risk of secondary cancers, particularly acute myeloid leukemia (AML). The treatments kill cancer cells by damaging DNA but may also cause hidden, latent damage to the DNA of normal cells, which may eventually cause new cancers. New research indicates that cancer patients receiving chemotherapy are nearly five times as likely as the general population to be diagnosed with treatment-related AML (t-AML), a risk especially high in the first 5 years after treatment with alkylating drugs (or radiation) but that may develop up to 10 years afterward.

“As well as finding significant variation in AML rates over 30 years, we found that chemotherapy alone may raise the risk of secondary cancers, which we previously thought applied only to radiation,” said Lindsay Morton, Ph.D., primary author of the study (Blood, Feb. 14, 2013) and investigator at the National Cancer Institute’s division of cancer epidemiology and genetics. Among 426,068 study patients drawn from the Surveillance, Epidemiology, and End Results (SEER) database, treatment for non-Hodgkin lymphoma accounted for the greatest increase in AML, followed by myeloma.

“We also found that since 2000, treatment-related secondary cancers increased among esophageal, cervical, and prostate cancer patients, and since the 1990s, in bone,joint and endometrial cancers,” said Morton. Risk of t-AML, which is extremely difficult to treat, or other secondary cancers should be calculated into all treatment decisions, Morton said.

“This is the first research since the 1980s to document treatment changes and risk of AML over time in a large cohort of patients,” said Margaret Tucker, M.D., director of the human genetics program and acting director of the division of cancer …(requires paid subscription to continue reading)

 

From Bench to Bedside: Lessons Learned in Translating Preclinical Studies in Cancer Drug Development

 
Blogger's Note: numerous ovarian cancer studies referenced

open access

"The development of targeted agents in oncology has rapidly expanded over the past 2 decades and has led to clinically significant improvements in the treatment of numerous cancers. Unfortunately, not all success at the bench in preclinical experiments has translated to success at the bedside. As preclinical studies shift toward defining proof of mechanism, patient selection, and rational drug combinations, it is critical to understand the lessons learned from prior translational studies to gain an understanding of prior drug development successes and failures. By learning from prior drug development, future translational studies will provide more clinically relevant data, and the underlying hope is that the clinical success rate will improve and the treatment of patients with ineffective targeted therapy will be limited.

Because standard chemotherapy demonstrates limited efficacy against a range of adult solid tumor malignancies, there has been an impetus toward the development of targeted agents in oncology. Likewise, there has been a shift of translational research away from simple screening studies of activity in preclinical models toward studies that define proof of mechanism, patient selection, and rational drug combinations. These strategies are substantially changing the preclinical rationale used to drive clinical development. Although these more robust preclinical studies have successfully guided the development of targeted agents in several tumor types, not all success at the “bench” has translated to success at the “bedside.” As preclinical models become more sophisticated, translational studies of targeted agents will have the potential to produce more clinically relevant data not only to guide “go/no-go” decisions but also to investigate resistance pathways and rational drug combinations. This review will provide examples of lessons learned from prior preclinical studies used in the development of targeted agents and addresses strategies moving forward..... 

Sections:

Epidermal Growth Factor Receptor Targeted Agents

Lessons Learned From EGFR Inhibition

Targeted Therapies Against Drivers of Oncogenesis

Lessons Learned in Targeted Therapies Against Drivers of Oncogenesis

Targeting Angiogenesis

Lessons Learned From Angiogenesis

Targeting Basic Cellular Processes

Lessons Learned From Targeting Basic Cellular Processes

Preclinical Models and Prediction of Pharmacokinetics and Toxicity

Limitations in Preclinical Models and Future Directions