OVARIAN CANCER and US

Tuesday, October 01, 2013

Disruptive Women in Health Care

Disruptive Women in Health Care

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The Fate of Whistleblowers in Nonprofit Organizations

abstract

"...This study finds that there is little difference in how whistleblowers are treated in the three sectors of our economy. In the majority of cases in this sample, the organizational managers against whom the whistleblowers level claims of wrongdoing, seek quickly to discredit, defame and terminate them.....

Over half of drug ad claims potentially misleading

healthnewsreview

"The researchers remind us that “consumers may see up to 30 hours of TV drug ads each year while only spending 15 to 20 minutes on average at each visit with their primary care physician."

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for the treatment of advanced epithelial ovarian carcinoma: Upfront therapy, at first recurrence, or later?

Aim

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS

HIPEC) has been proposed as treatment for advanced epithelial ovarian carcinoma (EOC). No consensus exists on when to administer CRS

HIPEC during the natural history of the disease, namely, as upfront therapy, at first recurrence, or at second or subsequent recurrence.

Patients and methods

We analyzed a series of patients with advanced EOC collected prospectively in an institution with a peritoneal malignant disease treatment program. Patients were treated with CRS

HIPEC upfront, at first recurrence, and at second or subsequent recurrence.

Results

We treated 42 patients: 15 upfront, 19 at first recurrence, and 8 at second or subsequent recurrence. Cytoreduction was complete (CC0) in 75% of cases; residual disease was <2.5 mm (CC1) in 25%. Severe morbidity (CTCAE v.3.0, grade 3–4) was 26%, and hospital mortality was 7%. After a median follow-up of 24 months, median overall survival was 77.8 months for patients treated upfront, 62.8 months for patients treated at first recurrence, and 35.7 months for patients treated at second or subsequent recurrence. Disease-free survival was 21.1 months, 18 months, and 5.7 months, respectively. Overall survival in the upfront and first recurrence groups was similar, and statistically significant differences with the second recurrence group were identified (p

0.03).

Conclusions

Treatment of advanced EOC using CRS

HIPEC is promising in terms of overall survival and disease-free survival when administered as upfront and at first recurrence therapy. These results warrant further evaluation in a randomized trial.

Phase I dose escalation study of the PKCι inhibitor aurothiomalate for advanced non-small-cell lung cancer, ovarian cancer, and pancreatic cancer

abstract

Protein kinase C iota (PKCι) is overexpressed in non-small-cell lung cancer, ovarian, and pancreatic cancers, where it plays a critical role in oncogenesis. The gold compound aurothiomalate (ATM) has been shown to inhibit PKCι signaling and exerts potent antitumor activity in preclinical models. We sought to determine the maximum tolerated dose (MTD) of ATM. We conducted a phase I dose escalation trial of ATM in patients with non-small-cell lung cancer, ovarian or pancreatic cancer. Patients received ATM intramuscularly weekly for three cycles (cycle duration 4 weeks) at 25, 50, or 75 mg in a 3+3 design. The dose was not escalated for individual patients. Blood samples were analyzed for elemental gold levels. Patients were evaluated every 4 weeks for toxicity and every 8 weeks for response. Fifteen patients were enrolled in this study. Six patients were treated at 25 mg, seven at 50 mg, and two at 75 mg. There was one dose-limiting toxicity at 25 mg (hypokalemia), one at 50 mg (urinary tract infection), and none at 75 mg. There were three grade 3 hematologic toxicities. The recommended MTD of ATM is 50 mg. Patients received treatment for a median of two cycles (range 1–3). There appeared to be a dose-related accumulation of steady-state plasma concentrations of gold consistent with linear pharmacokinetics. In summary, this phase I study was successful in identifying ATM 50 mg intramuscularly weekly as the MTD. Future clinical investigations targeting PKCι are currently in progress.

Current strategies to minimize toxicity of oxaliplatin: selection of pharmacogenomic panel tests

abstract

Oxaliplatin is an anticancer drug routinely used to treat colorectal, gastroesophageal, ovarian, breast, head/neck, and genitourinary cancers. Discontinuation of oxaliplatin treatment is mostly because of peripheral neuropathy, more often than for tumor progression, potentially compromising patient benefit. Several strategies to prevent neurotoxicity have so far been investigated. To overcome this life-threatening side effect, while taking advantage of the antineoplastic activities of oxaliplatin, we describe in detail recent findings on the underlying mechanisms of genetic variants associated with toxicity and resistance to oxaliplatin-based chemotherapy in colorectal cancer. A comprehensive panel of eight polymorphisms, previously validated as significant markers related to oxaliplatin toxicity, is proposed and discussed. In addition, the most common available strategies or methods to prevent/minimize the toxicity were described in detail. Moreover, an early outline evaluation of the genotyping costs and methods was taken in consideration. With the availability of individual pharmacogenomic profiles, the oncologists will have new means to make treatment decisions for their patients that maximize benefit and minimize toxicity. With this purpose in mind, the clinician and lab manager should cooperate to evaluate the advantages and limitations, in terms of costs and applicability, of the most appropriate pharmacogenomic tests for routine incorporation into clinical practice.

Current clinical trials with polo-like kinase 1 inhibitors in solid tumors

abstract

Significant advances in cancer treatment have resulted from the targeted cancer therapy by understanding the process of malignant transformation. Polo-like kinase 1 (PLK1) has been investigated as a target for cancer therapy for several years. Recently, anticancer drug candidates targeting PLK1 have been developed. To investigate the significance of PLK1 inhibitors in cancer patients, the current clinical statuses of PLK1 inhibitors including BI 2536, volasertib, and GSK461364A were analyzed. Monotherapy with BI 2536, the first human study of PLK1 inhibitors, has been terminated now, but its combinational study is still available in several solid tumors. The second-generation PLK1 inhibitor volasertib has an improved pharmacokinetic profile, safety, and efficacy, which is currently being developed under phase I/II. GSK461364 has shown a greater sensitive antitumor effect in p53-mutated cancer compared with that of p53-wild type cancer cells in a preclinical study. However, it has to be coadministered with an anticoagulator because of the high incidence of venous thrombotic emboli in clinical studies. PLK1 inhibitors showed a favorable pharmacokinetic profile, safety, and efficacy in patients with solid tumors. Further investigation with the use of PLK1 inhibitors in cancer patients who have mutated p53 or Ras and a high level of PLK1 as biomarkers is needed to consider the context and evaluation criteria of therapy.

Promestriene, a specific topic estrogen. Review of 40 years of vaginal atrophy treatment: is it safe even in cancer patients?

abstract

Urogenital symptoms resulting from estrogen deficiency are common problems that impair quality of life and sexuality. Potentially, one out of three postmenopausal women could benefit from a vaginal estrogen therapy, but the fear of systemic absorption limits its use. Promestriene used vaginally to relieve vaginal atrophy is a locally effective estrogen that has not shown systemic estrogenic effects. Thus, it could be a first-line option for those who necessitate a minimal or ideally no vaginal absorption, particularly in symptomatic cancer patients. There are little data available in the literature, mostly consisting of small, open-label, short duration studies, and few randomized-controlled studies. After a long-term market experience (almost 40 years), in 34 countries, and millions of pieces prescribed, the side effects were very rarely reported in pharmacovigilance data, whereas the effectiveness to relieve atrophy was good. To further improve promestriene safety, especially in estrogen-sensitive cancer patients, a very low dose is used from the beginning, starting from half or less of the usual dose, and then gradually increased till the minimum effective dose, which could further reduce its already minimal vaginal absorption.

HRT Risks May Vary by Type of Estrogen Drug (includes video)

medpage

Action Points

For postmenopausal women, CEE use was associated with a higher risk of incident venous thrombosis and possibly myocardial infarction than estradiol use.
Note that CEEs were not associated with an increased risk of ischemic stroke compared with estradiol.

Gynecologic Cancers Symposium Puts Emphasis on Unsettled Questions - Philadelphia Oct 5th

Symposium

Hot topics, emerging therapies, and tough cases from the front lines of patient care will be featured during the 9th Annual International Symposium on Ovarian Cancer and Gynecologic Malignancies,® scheduled for October 5 in Philadelphia.

The one-day meting, which Physicians’ Education Resource (PER) is hosting, will bring together noted experts in the field to dissect some of the most pressing questions about choosing the best strategies for treating patients.

Maurie Markman, MD, one of the meeting’s course directors, said the content would appeal to medical oncologists, gynecologic oncologists, surgeons, and any other healthcare professionals who work with patients diagnosed with gynecologic cancers. - See more at: http://www.onclive.com/publications/oncology-live/2013/august-2013/Gynecologic-Cancers-Symposium-Puts-Emphasis-on-Unsettled-Questions#sthash.sOLkmIfr.dpuf

Adverse reactions to targeted and non-targeted chemotherapeutic drugs with emphasis on hypersensitivity responses and the invasive metastatic switch

Abstract

$39.95 / €34.95 / £29.95 *

More than 100 drugs are used to treat the many different cancers. They can be divided into agents with relatively broad, non-targeted specificity and targeted drugs developed on the basis of a more refined understanding of individual cancers and directed at specific molecular targets on different cancer cells. Individual drugs in both groups have been classified on the basis of their mechanism of action in killing cancer cells. The targeted drugs include proteasome inhibitors, toxic chimeric proteins and signal transduction inhibitors such as tyrosine kinase (non-receptor and receptor), serine/threonine kinase, histone deacetylase and mammalian target of rapamycin inhibitors. Increasingly used targeted vascular (VEGF) and platelet-derived endothelial growth factor blockade can provoke a range of pathological consequences. Many of the non-targeted drugs are cytotoxic, suppressing haematopoiesis as well as provoking cutaneous eruptions and vascular, lung and liver injury. Cytotoxic side effects of the targeted drugs occur less often and usually with less severity, but they show their own unusual adverse effects including, for example, a lengthened QT interval, a characteristic papulopustular rash, nail disorders and a hand–foot skin reaction variant. The term hypersensitivity is widely used across a number of disciplines but not always with the same definition in mind, and the terminology needs to be standardised. This is particularly apparent in cancer chemotherapy where anti-neoplastic drug-induced thrombocytopenia, neutropenia, anaemia, vascular disorders, liver injury and lung disease as well as many dermatological manifestations sometimes have an immune basis. The most insidious of all adverse consequences of targeted therapies, however, are tumour adaptation, increased malignancy and the invasive metastatic switch seen with anti-angiogenic drugs that inhibit the VEGF-A pathway. Adverse reactions to 44 non-targeted and 33 targeted, frequently used, chemotherapeutic drugs are presented together with discussions of diagnosis, premedications, desensitizations and importance of understanding the mechanisms underlying the various drug-induced reactions. There is need for wide-ranging acceptance of what constitutes a hypersensitivity reaction and for allergists to be more involved in the diagnosis, treatment and prevention of chemotherapeutic drug-induced hypersensitivity reactions.

Bevacizumab and micrometastases: Revisiting the preclinical and clinical rollercoaster (solid tumors)

abstract

The use of bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), in combination with standard therapeutic approaches, has offered clinical benefit for patients with advanced colorectal, breast, ovarian, renal, non small-cell lung cancer and glioblastoma. However, the strategy of administering bevacizumab until disease progression has been challenged by certain preclinical evidence, suggesting that prolonged exposure to anti-VEGF treatment may elicit an adaptive-evasive response, resulting in a more aggressive tumor phenotype. Moreover, the use of bevacizumab in adjuvant chemotherapeutic regimens has led to less promising results than expected. Despite our poor understanding of how bevacizumab acts in micrometastatic disease, numerous clinical trials (involving >20,000 cancer patients) are ongoing or are planned to test the therapeutic benefit in the adjuvant setting. The discrepancy of bevacizumab's efficiency in the two settings calls into question the validity of current strategies that use similar treatment regimens for early and advanced disease. Herein, we review the mechanisms of bevacizumab activity in the macro- as compared to the micrometastatic environment and discuss possible alternative strategies in the adjuvant setting that might spur attention for future clinical trials. Rather than providing an encyclopedic survey of the literature, we highlight exemplary principles.
© 2013.

KEYWORDS:

BMDC, Bone marrow derived cells, CPC, Circulating progenitor cells, DFS, Disease-free survival, GBM, Glioblastoma multiform, NSCLC, Non small-cell lung cancer, OS, Overall survival, SNP, Single nucleotide polymorphism, TKI, Tyrosine kinase inhibitor, VEGF, VEGFR, Vascular endothelial growth factor, Vascular endothelial growth factor receptor, adjuvant therapy, bevacizumab, mCRC, mRCC, metastatic colorectal cancer, metastatic renal-cell cancer, micrometastases, solid tumors

it gets complicated - part 11

Cediranib Boosts Survival in Recurrent Ovarian Cancer

medscape

EMA (European Medicines Agency) accepts file for AstraZeneca PARP inhibitor (olaparib)

pharma news

Assessment of Paclitaxel-Induced Neuropathy - ClinicalTrials.gov

ClinicalTrials.gov

This study is currently recruiting participants.

Verified September 2013 by University of Chicago

Sponsor:

Information provided by (Responsible Party):

University of Chicago

ClinicalTrials.gov Identifier:

NCT01953159

First received: September 25, 2013

Last updated: September 27, 2013

Last verified: September 2013

History of Changes

Purpose

The purpose of this study is to collect clinical data, blood samples, and self reported symptoms from patients that experience unusually severe neuropathy after treatment with paclitaxel. This data will be used to develop predictive markers for neuropathy. Blood samples will be used to create induced pluripotent stem (iPS) cells and eventually artificial nerve cells to be used to study neuropathy in the lab.

Condition	Intervention
Cancer, Breast Cancer, Ovarian Cancer	Other: Blood Collection Other: Patient Questionnaires

McMaster University > CSBL > Standardized Patient Program

McMaster - an example

The Standardized Patient Program is a sub-division of the Centre for Simulation-Based Learning (CSBL) and coordinates the use of standardized patients (SPs). A standardized patient is a healthy person who is trained to realistically and accurately reproduce a history, physical and/or emotional medical scenario that a real patient would present. Standardized patients provide faculty and students opportunities to teach, assess, and refine a variety of skills, including communication, interview, diagnostic, and clinical skills.
The Standardized Patient Program is a fundamental resource for curriculum. It provides a unique and optimal environment to learn because it is risk-free and controllable. Students have the ability to explore techniques without causing harm, while SPs can be 'fast-forwarded', 'rewound', 'paused' or 'repeated' to various points of a simulation........

Ratings of Physician Communication by Real and Standardized Patients + blogger's opinion

Blogger's Note/Opinion: looks like Wiki and this review are at odds with each other; there is no 'magic' in this aka. 'you can't know what you don't feel' at this has been a rather large point for many years - no PhD required; some feel that using standardized patients is ethical as opposed to 'using' real patients; without 'using' real patients we will never get to what matters, what is important etc...this observation includes standardized patients who involve themselves in clinical trial protocols outside of their area of knowledge; for years there has been a very slow uptake on involving real patients in research (aside from clinical trials obviously) - a fact that is recognized and in of itself amazing; when real patients are involved the question remains of impact

open access

"....For these reasons, it is not possible from these data to determine for certain the reasons for the low correlations between real and standardized patient ratings. It is not clear whether they are primarily due to differences in context (eg, longitudinal relationship vs onetime visit), methods of administration for the HCCQ scale, or real differences in how well these 2 methods assess a key aspect of physician-patient communication, autonomy supportiveness. Further research using comparable types of visits (eg, new patients) and methods (post visit assessment by real patients) is needed to clarify these important questions.

In conclusion, we found that unannounced standardized patient ratings have better psychometric properties than real patients’ ratings of physicians’ communication behaviors, and that real and standardized patient ratings correlated poorly. These findings raise questions regarding the validity of patient ratings alone for recredentialing physicians or for pay-for-performance incentive programs and the potential usefulness of multiple methods for studying physician interactional behavior.²

Monday, September 30, 2013

2013 European Cancer Congress - news

2013 ECCO

Women with recurrent ovarian cancer survive longer after treatment with cediranib

Womedical news

Women with ovarian cancer that has recurred after chemotherapy have survived for longer after treatment with a biological therapy called cediranib, according to new results to be presented today (Monday) at the 2013 European Cancer Congress (ECC2013).

"Cediranib, which is taken in pill form, is an inhibitor of a cell signalling process involved in formation of tumour blood vessels, essential for tumour growth, and it is the first oral inhibitor of its kind to show an improvement in the time before patients' disease progresses and in overall survival. The drug is a tyrosine kinase inhibitor, a type of biological therapy that blocks vascular endothelial growth factor (VEGF) receptors, which control the development of blood vessels required for growing tumours.
Professor Jonathan Ledermann, Professor of Medical Oncology at UCL Cancer Institute, University College London, presented first results from ICON6, an international randomised, double-blind, academic clinical phase III trial of cediranib......

(U.S.) Cancer Insurance Checklist

THIS CHECKLIST WAS CREATED THROUGH A PARTNERSHIP OF:

The Assistance Fund, Association of Community Cancer Centers, Avalere Health, Cancer
Support Community, Chronic Disease Fund, Cutaneous Lymphoma Foundation, International
Myeloma Foundation, The Leukemia & Lymphoma Society, Living Beyond Breast Cancer,
Lung Cancer Alliance, Melanoma Research Foundation, Men’s Health Network, National
Coalition for Cancer Survivorship, Oncology Nursing Society, Ovarian Cancer National
Alliance, Patient Advocate Foundation/National Patient Advocate Foundation, Patient
Services, Inc., Prevent Cancer Foundation

abstract

Objective: This study evaluated the incidence of postoperative morbidities, focusing specifically on pancreatic fistulas, after a splenectomy performed as part of cytoreductive surgery for the treatment of ovarian cancer.

Methods: A retrospective chart review was performed for all the patients with ovarian, tubal, or peritoneal cancer who underwent splenectomy during a 5-year period. Patient-, disease-, and surgery-related data were collected. Pancreatic fistulas were identified when the drainage fluid obtained via a surgically placed drain had an amylase content greater than 3 times the normal serum value after postoperative day 3.

Results: A splenectomy was performed in 21 patients. Postoperative pancreatic fistulas developed in 6 patients (29%). Of these 6 patients, 2 had no symptoms and did not require specific treatment for their pancreatic fistulas. Therapeutic intervention was required in the remaining 4 patients. The durations of oral feeding prohibition and the use of a peripancreatic drain were longer in the patients with a pancreatic fistula than in those without a pancreatic fistula. Overall, the pancreatic fistulas were managed conservatively or using minimally invasive procedures. Staple-line reinforcement seemed to be an effective means of closing the transected stump during the splenectomy, compared with the standard stapling technique.

Conclusions: Elevated amylase levels in the drainage fluid reflect the patient’s actual condition better than serum amylase levels. We recommend the intraoperative placement of a peripancreatic drain and postoperative measurement of amylase concentrations in the drainage fluid to identify the development of pancreatic fistulas and to facilitate the management of this complication.

Preoperative Fluorine 18 Fluorodeoxyglucose Tumoral Uptake Ratio Between Upper and Lower Abdomen in Primary Advanced-Stage Ovarian Cancer

abstract

Objective: The objective of this study was to assess whether the ratio of upper abdomen (UA) to lower abdomen (LA) (relative to the umbilicus) standardized fluorine 18 fluorodeoxyglucose uptake, as measured by preoperative positron emission tomography and computed tomography, is predictive of recurrence, survival, and suboptimal cytoreduction (residual tumor >1.0 cm) in advanced-stage ovarian cancer (AOC).

Methods: Positron emission tomography/computed tomography before surgical staging was performed in 159 AOC patients. The ratio between the highest maximum standardized uptake value (SUV_max) in the UA and the LA was expressed as UA/LA SUV_max. Clinicopathological characteristics and follow-up information were collected retrospectively. Cox proportional hazards analysis was used to identify prognostic factors for recurrence and survival. Logistic regression analysis was used to identify predictors of suboptimal cytoreduction.

Results: The median age and follow-up period were 55 years (range, 27–80 years) and 32 months (range, 1–92 months), respectively; 133 and 26 patients had stage III and IV disease, respectively. There were 120 and 54 cases of recurrence and disease-specific death, respectively. Multivariate analysis showed that recurrence was associated significantly with high UA/LA SUV_max (P < 0.05; hazard ratio [HR], 4.902; 95% confidence interval [CI], 2.521–9.531) and suboptimal cytoreduction (P < 0.05; HR, 2.431; 95% CI, 1.561–3.788), and that disease-specific death was significantly associated with high UA/LA SUV max (P < 0.05; HR, 2.777; 95% CI, 1.270–6.075), suboptimal cytoreduction (P < 0.05; HR, 1.951; 95% CI, 1.080–3.524), and histology (P < 0.05; HR, 4.134; 95% CI, 1.676–10.196). Upper abdomen/lower abdomen SUV_max was the only independent predictor of suboptimal cytoreduction (P < 0.05; odds ratio, 4.644; 95% CI, 1.676–12.862).

Conclusions: High preoperative UA/LA SUV_max was significantly associated with poor prognosis and may be predictive of suboptimal cytoreduction in AOC. This parameter may be considered in the treatment of AOC patients.

Specialized Pathology Review in Patients With Ovarian Cancer: Results From a Prospective Study

abstract

Background: A significant number of ovarian borderline tumors (BOTs) and metastatic nonovarian primaries are erroneously diagnosed as ovarian carcinomas. If BOTs are misdiagnosed as cancer, patients may not only experience nonbeneficial morbidity but may have to cope with an incorrect diagnosis of cancer for the rest of their lives. In cases of metastatic disease mistaken for an ovarian primary, more adequate therapeutic modalities may be withheld from some patients. Finally, clinical trials may be biased through unintended disregard of histological inclusion criteria.

Methods: Patients were recruited for central pathology review according to a translational subprotocol of a prospectively randomized phase 3 study led by the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) Study Group. All original slides were requested, and a specialized central pathology review was performed by experienced gyneco-pathologists. In cases of clinically relevant diagnostic discrepancies, the pathologist responsible for the original diagnosis was contacted. If a given discrepancy could not be resolved, a panel of experts was involved for clarification.

Results: Four hundred fifty-four patients with an original diagnosis of ovarian, tubal, or peritoneal epithelial carcinoma were recruited. In 6.8% (31 patients), a major diagnostic discrepancy of clinical relevance was found. Most frequently (15 patients), serous BOT had been misdiagnosed as invasive cancer. Ovarian metastases constituted the second most frequent misdiagnosis (13 patients). Minor discrepancies not affecting patient treatment were found in 28.2% (128 patients).

Conclusions: Specialized central pathology review could help to avoid overtreatment of patients with BOT and inappropriate treatment of patients with ovarian metastases. The implementation of a specialized case review process may translate into enhanced patient safety in clinical trials of ovarian carcinomas. Furthermore, central pathology review may increase the rigor and ultimately the transferability of clinical research into practice and should therefore become a standard procedure in study protocols evaluating new therapies.

it gets complicated

tweetcloud

older version/example:

#MomInHospital | Wachter's World

Blogger's Note: this is not about ovarian cancer but about a physician's Mom's stay in hospital and it covers a lot of ground eg. twitter, bowel obstructions, hospital rounds, plain english communication (in elderly patients) etc...

#MomInHospital | Wachter's World

NICE to update ovarian cancer drug guidelines - media

media

Clinical Oncology News - What Do Patients Think About _____?

Clinical Oncology News - What Do Patients Think About _____?

"....I provide these examples to emphasize the point that it is not appropriate to simply assume we understand the patient’s perspective or knowledge of a cancer topic without inquiring in a very formal manner, and ensuring an appropriate sample size that represents all of the relevant constituencies.
For health care policy, the role of patients will be different from the examples cited above, but should be no less relevant. When determining the societal value associated with the treatment of metastatic cancer, for example, we should not arbitrarily accept the utility of such therapy based solely on a modest extension of the length of life....

September is Ovarian Cancer Awareness Month: Fact Sheet: What raises a woman’s chance of getting ovarian cancer?

What raises a woman’s chance of getting ovarian cancer?

There is no way to know for sure if
you will get ovarian cancer. Most
women get it without being at high
risk. However, the following factors
may increase a woman’s risk for
ovarian cancer:

• Being middle-aged or older.

• Having close family members
(such as your mother, sister, aunt,
or grandmother) on either your
mother’s or your father’s side
who have had ovarian cancer.

• Having had breast, uterine, or
colorectal cancer. (BRCA 1 or BRCA2; Lynch Syndrome)

• Having an Eastern European
(Ashkenazi) Jewish background.
• Having never given birth or
having had trouble getting
pregnant.

• Having endometriosis (a
condition where tissue from
the lining of the uterus grows
elsewhere in the body).

If you have one or more of these
factors, it does not mean you will get
ovarian cancer. But you should speak
with your doctor, nurse, or other health
care professional about your risk.

Sunday, September 29, 2013

Toronto doctor develops ‘O.R. black box’ to catch potentially deadly errors made during surgeries

media

"Teodor Grantcharov’s idea for transforming one of the riskiest areas of medicine is so provocative, the Toronto doctor figures it could never have been launched in the litigious world of American health care.
Inspired by a crucial element of aircraft-accident investigations, the respected surgeon has developed an “O.R. black box” to help get to the bottom of potentially harmful errors made during operations — errors that are blamed for hundreds of deaths in Canada every year. (and around the world - see WHO Patient Safety and AHRQ amongst others)
The equipment simultaneously records video and audio of what is happening both in the operating room and inside the patient’s body, generating a detailed electronic log of the treatment, mistakes and all.
The idea is not to aid personal-injury lawyers, but to encourage better work and identify when and why problems occur, so they can be prevented in future.

The system is being tested now at Toronto’s St. Michael’s Hospital, but Dr. Grantcharov envisions the day the equipment becomes a standard feature of operating rooms around the world.
“I believe this has the potential to change the way we practise surgery,” he said.
“I’m sure some people will feel threatened, like pilots felt threatened when the black box was first introduced,” said the physician. “But … we are a high-risk, high performance industry and all of us can be patients one day, and we would like to make sure everybody performs to the standard.”.....

Inherited Genetic Susceptibility to Breast Cancer: The Beginning of the End or the End of the Beginning?

open access

Clovis Oncology

website

Ongoing Phase I Monotherapy Study of Rucaparib in Patients with Solid Tumors Demonstrates Clinical Activity, Establishes Dose and Schedule (Clovis Oncology)

news

Clovis Oncology (NASDAQ:CLVS) today announced updated results from an ongoing Phase I/II monotherapy study of rucaparib, the Company's oral, potent, small molecule poly (ADP-ribose) polymerase (PARP) inhibitor being developed for the treatment of ovarian cancer. Data from the Phase I dose-escalation portion of this Phase I/II study are being presented today at a poster session during the European Cancer Congress 2013 in Amsterdam.
"We've seen significant clinical activity with one complete response in breast cancer and six partial responses in ovarian, breast and pancreatic cancers to date, and a disease control rate in patients with germline BRCA mutant ovarian (platinum-sensitive and platinum-resistant) cancer of 100% and 63% at 12 and 24 weeks, respectively. I am pleased to be participating in the Phase II and pivotal Phase III trials (ARIEL2 and ARIEL3) which aim to build on the clear activity of rucaparib in BRCA-mutant ovarian cancer and prospectively identify and test other genetic mutations associated with sensitivity to PARP inhibition in ovarian cancer. This approach has the potential to broaden applicability of PARP inhibitor treatment for ovarian cancer as well as other solid tumors and hopefully benefit many patients," said Dr. Rebecca Kristeleit, Clinical Senior Lecturer and Consultant Medical Oncologist UCLH and UCL Cancer Institute in London.......

Urothelial Cancer and the Diagnosis of Subsequent Malignancies (Lynch Syndrome patients)

abstract

Purpose: We examine the likelihood of a second primary malignancy diagnosis following the diagnosis of urothelial cancer.

Methods: We identified subjects from the Manitoba Cancer Registry diagnosed with urothelial cancer between April 1, 1985 and December 31, 2007. Data were collected on all subsequent new cancer diagnoses. Standardized incidence ratios (SIRs) were calculated for each major cancer type, matched with the general population by age, sex and period. Further analysis was undertaken stratifying by morphology and invasiveness. The results in males were examined with and without prostate cancer. A competing risk model was used to analyze the data controlling for death.

Results: Of the 4412 included urothelial cancer cases, 712 patients (16.1%) subsequently developed a second primary malignancy. Risks were highest within 1 year of diagnosis persisting for 5 years. This risk was highest in males aged less than 70 (SIR = 6.25; 95% Confidence Interval [CI] 5.08-7.04). Overall, the risk was similar between the sexes (female SIR: 1.30, CI 1.09-1.54; males 1.42, CI1.31-1.54; males excluding prostate SIR: 1.22 CI 1.11-1.35). There was an increased relative risk for developing a second primary for cancers of the kidney (male), lung, breast (female) and prostate. Papillary cancers were associated with increased relative risk of developing lung, prostate, and breast (female and male) cancer. In the competing risks model, patients diagnosed with a papillary or insitu urothelial cancer were more likely to be diagnosed with a second primary than non-papillary and invasive disease, respectively.

Conclusions: Those diagnosed with urothelial cancer have an increased probability of having a second primary cancer detected within the subsequent 5 years, even when prostate cancer is excluded. Papillary tumours in particular may provide a warning for subsequent malignancy.

BioMarin Provides Updated Phase 1/2 Data on BMN 673 in Breast Cancer at the European Cancer Congress 2013 - MarketWatch

media

PLOS ONE: Integrated Analysis of Mismatch Repair System in Malignant Astrocytomas (Lynch Syndrome/brain cancer)

open access

Abstract

Malignant astrocytomas are the most aggressive primary brain tumors with a poor prognosis despite optimal treatment. Dysfunction of mismatch repair (MMR) system accelerates the accumulation of mutations throughout the genome causing uncontrolled cell growth. The aim of this study was to characterize the MMR system defects that could be involved in malignant astrocytoma pathogenesis. We analyzed protein expression and promoter methylation of MLH1, MSH2 and MSH6 as well as microsatellite instability (MSI) and MMR gene mutations in a set of 96 low- and high-grade astrocytomas......
"We have performed a molecular characterization of MMR system defects in malignant astrocytomas and we have evaluated the influence of these alterations in patient outcome. Specifically, we have investigated the expression profile and the promoter hypermethylation status of MLH1, MSH2 and MSH6 genes, as well as the MSI levels in pretreated low- and high-grade primary astrocytomas. We have also conducted a mutational analysis of MMR genes in tumors with MMR defective function.........

In summary, our results demonstrate that MMR system alterations are a frequent event in malignant astrocytomas. We suggest that analysis of MMR genes allows to define a subset of astrocytomas with different outcome and could help to search for new therapeutic strategies.

“They liked it if you said you cried”: how medical students perceive the teaching of professionalism

open access

2011 Hereditary ovarian cancer: recent molecular insights and their impact on screening strategies

abstract

Purpose of review: This review will focus on the implications of BRCA status in the patient with high-grade serous ovarian cancer, the differences between BRCA1 and BRCA2 mutations, and the most effective risk-reducing strategies.

Recent findings: Women with BRCA-associated epithelial ovarian cancer represent a unique group who commonly are diagnosed at a younger age, have advanced high-grade serous disease, have improved sensitivity to platinum-based chemotherapy in both the upfront and recurrent setting, and have an overall improved prognosis. Promising novel therapeutic agents such as poly (ADP-ribose) polymerase inhibitors have increased activity in patients with inherited BRCA mutations and may also have a role in patients with noninherited tumors that have decreased BRCA activity. Risk-reducing salpingo-oophorectomy (RRSO) is effective in decreasing risks of both breast and gynecologic cancer in women with BRCA mutations. However, when counseling women at inherited risk, the inherent phenotypical differences between BRCA1 and BRCA2 mutations must be considered.

Summary: Patients with BRCA-associated epithelial ovarian cancer have improved response to platinum-based chemotherapy, improved survival, and may be appropriate candidates for treatment with novel targeted therapies. RRSO remains the most effective risk-reduction strategy in women with BRCA mutations.

2011 Lymphadenectomy in ovarian cancer: standard of care or unnecessary risk

abstract

Purpose of review: The clinical significance of lymphadenectomy in ovarian cancer is controversial. In early ovarian cancer (EOC), it is the extent of the procedure that is the main focus of debate. In advanced disease [advanced ovarian cancer (AOC)], the issue is whether or not lymphadenectomy independently impacts survival. This review summarizes the current standard of care as it relates to the role of lymphadenectomy in ovarian cancer.

Recent findings: Lymphadenectomy in EOC is a diagnostic procedure in as much as it is an integral and mandatory part of a complete surgical staging. The required extent of the procedure, however, remains uncertain. It has been suggested that at least 10 nodes from different, predefined retroperitoneal sites should be the minimum number removed. Lymphadenectomy in AOC is of potential therapeutic value. The only published randomized clinical trial (RCT) showed no overall survival benefit after radical/systematic lymphadenectomy, although there was an impact on 6-month disease-free survival. Conversely, retrospective studies, a meta-analysis and a re-analysis of three RCTs in AOC do suggest an overall survival benefit for radical/systematic lymphadenectomy.

Summary: This review concludes with the recommendation that lymphadenectomy in EOC is a mandatory part of surgical staging and that a minimum of 10 nodes should be harvested from different retroperitoneal sites. In AOC, lymphadenectomy can be considered when intraperitoneal cytoreduction has been complete or when there are bulky nodes.

2011 Which is the better surgical strategy for newly diagnosed epithelial ovarian cancer: primary or interval debulking?

abstract - Current Opinion in Oncology journal

Purpose of review: Surgical debulking is a mainstay of therapy for epithelial ovarian cancer. The traditional timing of this surgery has been prior to chemotherapy, but this view has been challenged over the last decade. This review will focus on the recently completed phase III studies of surgical timing and discuss exceptions to the superior paradigm of neoadjuvant chemotherapy followed by interval debulking.

Recent findings: The two completed studies have shown that neoadjuvant chemotherapy followed by interval debulking is the superior strategy for stage IIIc and IV ovarian cancer compared to primary surgery followed by chemotherapy. Survival outcomes were the same, but the morbidity for the patient and cost to the system and patient were less with interval debulking. Exceptions to this sequence are potentially stage I or II patients and those stage III patients who can be optimally debulked so as to receive intraperitoneal chemotherapy.

Summary: Chemotherapy followed by interval debulking will result in fewer and simpler operations and lesser morbidity for the patients resulting in cost savings for the healthcare system and less inconvenience and toxicity for the patient with equivalent survival outcomes. As such it is the superior strategy.

Precursor Lesions and Prognostic Factors in Primary Peritoneal Serous Carcinoma

abstract

Primary peritoneal serous carcinoma (PPSC) is uncommon and precursor lesions and prognostic factors are incompletely understood or described. Charts of 22 women with PPSC were reviewed for clinical and pathology data. Glass slides were reviewed for areas of PPSC, ovarian surface epithelium (OSE), ovarian cortical inclusion cysts (OCICs), tubal epithelial atypia (TEA), and serous tubal intraepithelial carcinoma (STIC). p53 and p16 immunohistochemical staining was scored and expression between the sites was compared. PPSC outcome was correlated with biomarker expression and clinicopathologic variables. p53 and p16 scores were significantly higher among PPSC and tubes than OSE and OCICs. Approximately 64% of PPSC, 46% of fallopian tubes, and none of the OSE overexpressed both biomarkers. OCICs were more frequently negative. Tubal pathologies of STIC, TEA and/or p53 signatures were present in approximately 46% of PPSC cases and the association with tubal p53 overexpression was significant. Statistically significant associations between tubal pathologies, OSE and OCICs biomarker expression profiles and their PPSC expression profiles did not occur. The median overall survival was 53 months and low-grade tumors had a better prognosis (P=0.02). A role for p53 and p16 overexpression in the formation of some PPSC, and p53 overexpression in the generation of precursor tubal pathology was identified. The high frequency of tubal pathology overexpressing p53 and low frequency of OSE and OCICs expressing either biomarker highlights a possible precursor role for the tube in some PPSC. Tumor grade was the only significant prognostic factor.

Case Report: Association between Rash and a Positive Drug Response Associated with Vinorelbine in a Patient with Primary Peritoneal Carcinoma

Blogger's Note: skin rashes/outcomes have been reported in other cancers; also can denote an underlying malignancy and/or serious adverse event

abstract

Vinorelbine (Navelbine, VRL) is commonly used for platinum-resistant ovarian cancer and has been shown to be effective in patients with recurrent primary peritoneal carcinoma. Of VRL's major side effects, skin rash is uncommon, and, if it does occur, it is usually localized to site of injection. In this case report, a 71-year-old Hispanic female with primary peritoneal carcinoma received single agent VRL as fourth-line regimen, which she tolerated very well except for a skin rash related to VRL. The rash continued to progress throughout 6 cycles of VRL, and follow-up CT/PET scan demonstrated complete metabolic and radiological responses. We, therefore, believe that this rash was linked to VRL administration and correlated with response to therapy. Rash has been recognized as a useful surrogate marker with targeted agents such as cetuximab and erlotinib; to the best of our knowledge, this case report describes the first patient with a possible drug rash and its association with a positive outcome. This case report incites interest in further investigation of similar cases to support this observation, since there is a lack of reports of skin rash with VRL therapy.

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Perioperative and clinical outcomes in the management of epithelial ovarian cancer using a robotic or abdominal approach

abstract

Highlights

•: Compared to laparotomy, robotic surgery was feasible and effective.
•: Robotic operative times were reasonable, hospital stay and blood loss were reduced.
•: Debulking, one year survival, and recurrence rates were similar between groups.

Objective

To evaluate the feasibility and efficacy of robotic–assisted management of epithelial ovarian cancer.

Methods

Retrospective review of robotic-assisted or abdominal ovarian cancer cases presenting with pelvic mass, initial staging, or debulking after neoadjuvant chemotherapy performed by a single surgeon (2008-2012). Patient characteristics and outcomes were compared using chi-squared or student’s t-tests.