Authors Reply - Appropriate, timely referral to palliative care services: A name change will not help

 Reply to D. Milne et al

"Milne et al1 contend that changing the name “palliative care”
to “supportive care” would not change referral practices to palliative
care services and that education of patients and caregivers, as
well as physicians, is essential. They support this argument with
data from a qualitative study, in which they interviewed patients,
family caregivers, and health professionals. Our survey2 was not
designed to address the question of whether or not palliative care
should be renamed, and we therefore did not come to any conclusions
or recommendations in that regard. There are, however,
several pertinent results from the survey that can be used to address
the question of whether renaming the specialty could encourage
earlier referrals.......


REFERENCES (prior blog posting)
1. Milne D, Jefford M, Schofield P, et al: Appropriate, timely referral to
palliative care services: A name change will not help. J Clin Oncol doi: 10.1200/
JCO.2012.48.4493

Multiple Large Bowel Resections: Potential Risk Factor For Anastomotic Leak (in ovarian cancer)

abstract

OBJECTIVES:

Identify risk factors of anastomotic leak (AL) after large bowel resection (LBR) for ovarian cancer (OC) and compare outcomes between AL and no AL.

METHODS:

All cases of AL after LBR for OC between 01/01/1994-05/20/2011 were identified and matched 1:2 with controls for age (+/-5years), sub-stage (IIIA/IIIB;IIIC;IV), and date of surgery (+/-4years). Patient-specific and intraoperative risk factors, use of protective stomas, and outcomes were abstracted. A stratified conditional logistic regression model was fit to determine the association between each factor and AL.

Strides Made in Preventing Cancer, But Challenges Remain: Report - MedicineNet

 Blogger's Note: this quote is important as it is most often contrary to prevalent opinion/s that all cancers are directly/indirectly related to obesity; obesity is a health concern but not necessarily directly related to most cancers  ( 7 out of ~200 different types of cancer); of issue is the additional psychological (and other) burdens placed on cancer patients by those who are not informed and make superficial judgements

MedicineNet

".....One expert discussed the obesity-cancer connection.
"Over 116,000 cancers can be prevented every year if more Americans stay lean. It's not a silver bullet, but preventing obesity can help prevent cancer," said Alice Bender, nutrition communications manager at the American Institute for Cancer Research.
Bender said that right now, only about half of Americans are aware of the link between obesity and cancer. There are seven cancers that have good evidence linking them to obesity......

‘They’ve just got symptoms without science’: Medical trainees’ acquisition of negative attitudes towards patients with medically unexplained symptoms

abstract

Practical implications

Current medical training fails to equip doctors to engage with MUS and potentially fosters the development of unhelpful views of these patients. Informed teaching on diagnosis and management of MUS is necessary at a trainee level to limit the development of negative attitudes.

Myriad Genetics CEO Claims He Owns Your Genes - Forbes

media

Endometriosis-associated ovarian cancersPathogenesis and consequences on daily practice

Abstract


Endometriosis is considered as a tumor-like lesion under the World Health Organization (WHO) classification of ovarian tumors. Data from large cohort and case-control studies indicate that patients with a history of endometriosis have an increased risk of ovarian cancer. Recent findings suggest an association between endometriosis and the entire type 1 ovarian tumors group including clear-cell, endometrioid and low-grade serous carcinomas. However, current evidence is lacking to draw definitive conclusion whether this association represents causality or the sharing of common risk factors. Nevertheless, assumption that endometriosis could be a precursor of malignancy raises many issues about serial screening, surgical management and surveillance of endometriosis. Beyond these concerns, endometriosis-associated ovarian cancers seem to be a genuine clinical entity as regards clinicopathological features. In view of the high incidence of endometriosis (10 % of women of childbearing age), the low incidence of endometriosis-associated ovarian cancers and the psychological consequences for those women, systematic screening and surgical exploration seem very questionable in this context.

Cancer drug scandal: 137 Ontario patients die since receiving diluted chemo | Toronto Star - how many more?

media

"....The 26 additional patients discovered in London “begs the question how many more are still out there . . . and how many other drugs?” NDP Leader Andrea Horwath said at Queen’s Park.....

video via Women of Teal blog: Youtube - Your Cancer Team/SGO - On Your Side

blogger: Women of Teal

"....a wonderful video by the SGO which describes the role of every member of a women's gynecologic cancer team."

Friday, April 12, 2013

Your Cancer Team

Outside Slide Review in Gynecologic Oncology

Abstract
 

In gynecologic oncology, surgical and adjuvant therapy rely heavily on correct pathologic diagnosis. Thus, in-house review of outside pathologic slides and specimens has become routine within large tertiary referral centers. We sought to determine the impact of outside pathologic slide review on gynecologic oncology patient care and treatment. Gynecologic oncology cases between January 2007 and January 2012 were evaluated. Clinical information was gathered from comprehensive chart reviews and reports created after multidisciplinary treatment planning conferences. Discrepancies in diagnosis were identified as major if they resulted in a treatment alteration and minor if they did not impact care. Data were analyzed using descriptive statistics and the Fisher exact test. A total of 279 cases were identified and reviewed as part of the study—126 (45.2%) biopsy/cytology specimens and 153 (54.8%) surgical excision specimens. Minor discrepancies were noted in 25 reviewed cases (9%) and major discrepancies in 19 cases (6.8%). Among those patients in whom management was changed based on specialized pathologic review, 50% underwent additional surgery, 16% had their surgical plan modified, and 16% received adjuvant treatment or had their adjuvant treatment modified. In 235 cases (84.2%), institutional rereview of the outside slides/specimens did not result in a change in diagnosis. Diagnostic discrepancies were evenly distributed across all primary sites evaluated. The cost of outside pathologic review was estimated at $2,936 US dollars per change in diagnosis. Mandatory slide review in gynecologic oncology is important and results in diagnostic changes in approximately 16% of cases, with 43% of those changes impacting treatment.

26 more patients given diluted chemo drugs: hospital | Globalnews.ca (includes children)

Globalnews.ca

TORONTO – The number of cancer patients in Ontario and New Brunswick who received watered down chemotherapy drugs – some for more than a year – has climbed to more than 1,200.
The London Health Sciences Centre said Friday that 26 additional patients were identified during a second, expanded assessment of its files.
The latest discovery brings the total number of patients affected at the London, Ont., hospital to 691 – 651 adults and 40 children.......

paywalled: Diluted chemotherapy drugs affect 1200 patients in Canada : The Lancet Oncology

Diluted chemotherapy drugs affect 1200 patients in Canada : The Lancet Oncology

The Lancet Oncology, Early Online Publication, 12 April 2013

doi:10.1016/S1470-2045(13)70137-2Cite or Link Using DOI

Jennifer Wong

 

"Drug supplier Mezentco (Hamilton, ON, Canada) faces a class action lawsuit for the accidental dilution of two chemotherapy drugs supplied to five hospitals since February, 2012. The products affected are cyclophosphamide and gemcitabine, which are used to treat breast cancer, lung cancer, lymphoma, and leukaemia. After the issue was discovered at the Windsor Regional Hospital (Windsor, ON), an investigation revealed that the supplier had been improperly mixing the drugs, resulting in a 3—20% dil ..."

Meta-analysis of epoetin beta and darbepoetin alfa treatment for chemotherapy-induced anemia and mortality: Individual patient data from Japanese randomized, placebo-controlled trials - Ohashi - 2013 - Cancer Science - Wiley Online Library

Abstract

"Erythropoiesis-stimulating agents (ESA) reduce the need for transfusions and improve the quality of life in patients receiving chemotherapy, but several clinical trials have suggested that ESA might have a negative impact on survival. To evaluate the efficacy and safety of ESA, epoetin beta and darbepoetin alfa, including their impact on overall survival and thromboembolic events, we conducted an individual data-based meta-analysis of three randomized, placebo-controlled trials studying Japanese patients with chemotherapy-induced anemia. All trials were conducted in compliance with Good Clinical Practice. A total of 511 patients with solid tumor or lymphoma (epoetin beta or darbepoetin alfa, n = 273; placebo, n = 238) were included. The ESA significantly reduced the risk of transfusion (relative risk, 0.47; 95% confidence interval, 0.29–0.76). No significant effect of the ESA on overall survival was observed (unadjusted hazard ratio, 1.00; 95% confidence interval, 0.75–1.34). A prespecified subgroup analysis showed no strong interaction between the baseline hemoglobin concentration and the effect of ESA on overall survival. Among the ESA-treated patients, the highest hemoglobin achieved during the treatment period in each patient had no impact on mortality. No increase in thromboembolic events was observed in the ESA-treated patients (0.7% vs 1.7% placebo). The ESA reduced the risk of transfusion without a negative impact on the survival of patients with chemotherapy-induced anemia."

How hope can help you heal - CNN.com

CNN.com

"When he talks about hope, people's eyes glaze over more often than not. Nonetheless, Lopez believes hope is the stuff of change, recovery and healing.....

Progesterone receptors induce FOXO1-dependent senescence in ovarian cancer cells

open access

Abstract:

Loss of nuclear progesterone receptors (PR) and low circulating progesterone levels are associated with increased ovarian cancer (OC) risk. However, PR are abundantly expressed in a significant percentage of serous and endometrioid ovarian tumors; patients with PR+ tumors typically experience longer progression-free survival relative to those with PR-null tumors. The molecular mechanisms of these protective effects are poorly understood. To study PR action in OC in the absence of added estrogen (i.e., needed to induce robust PR expression), we created ES-2 OC cells stably expressing vector control or GFP-tagged PR-B (GFP-PR). Progestin (R5020) stimulation of ES-2 cells stably expressing GFP-PR induced cellular senescence characterized by altered cellular morphology, prolonged survival, senescence-associated β-galactosidase activity, G₁ cell cycle arrest and upregulation of the cell cycle inhibitor, p21, as well as the Forkhead-box transcription factor, FOXO1; these results repeated in unmodified ER+/PR+ PEO4 OC cells. PR-B and FOXO1 were detected within the same PRE-containing regions of the p21 upstream promoter. Knockdown of p21 resulted in molecular compensation via FOXO1-dependent upregulation of numerous FOXO1 target genes (p15, p16, p27) and an increased rate of senescence. Inhibition of FOXO1 (with AS1842856) or stable FOXO1 knockdown inhibited progestin-induced p21 expression and blocked progestin-induced senescence. Overall, these findings support a role for PR as a tumor suppressor in OC cells, which exhibits inhibitory effects by inducing FOXO1-dependent cellular senescence. Clinical “priming” of the PR-FOXO1-p21 signaling pathway using PR agonists may provide a useful strategy to induce irreversible cell cycle arrest and thereby sensitize OC cells to existing chemotherapies as part of combination “two-step” therapies.

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Image-guided intensity-modulated whole abdominal radiation therapy in relapsed epithelial ovarian cancers: A feasibility study.

Abstract

J Cancer Res Ther. 2013 Jan-Mar;9(1):17-21. doi: 10.4103/0973-1482.110343.

Source

Department of Radiation Oncology, Tata Memorial Centre, Mumbai, India.

Abstract

Background and Purpose: Advanced epithelial ovarian cancer is associated with high relapse rates. Various consolidative therapies, including whole abdominal radiation therapy (WAR), have been tried in the past with limited success. We report here a feasibility study and clinical outcome of WAR with helical tomotherapy (HT).
Materials and Methods: Eight patients with relapsed carcinoma ovary after standard treatment and deemed not suitable for further chemotherapy were treated with WAR using HT. All patients underwent intensity-modulated radiotherapy (IMRT) planning process and a dose of 25Gy/25#, at 1Gy/# to the whole of the abdomen [abdominal planning treatment volume (PTV)] with a simultaneous boost of 45Gy/25#, at 1.8Gy/# to the pelvic PTV was prescribed.
Results: There was an excellent coverage in both abdominal and pelvic PTVs.The V 95% (volume covered by the 95% isodose) and V 107% (volume receiving 107% dose) was 95.6 (±2.7)% and 2.6 (±0.5)% for abdominal PTV and 95.7 (±2.4)% and 0% for pelvic PTV, respectively. With a median follow-up of 15 months (10-24 months, mean: 14 months), 3 patients (out of 8 total patients) developed disease recurrence. All 3 recurred in the peritoneum, one progressed to intestinal obstruction and fatal septicemia.
Conclusion: WAR in recurrent/relapsed epithelial ovarian cancer is feasible with acceptable toxicities.

National Guideline Clearinghouse | Breast cancer follow-up and management after primary treatment: American Society of Clinical Oncology clinical practice guideline update.

March 1, 2013 update

also see: 
JCO guideline

Journal of Ovarian Research - No evidence for PALB2 methylation in high-grade serous ovarian cancer

open access

 Abstract (provisional)

Background

High-grade serous ovarian cancers are a distinct histological subtype of ovarian cancer often characterised by a dysfunctional BRCA/Fanconi anaemia (search) (BRCA/FA) pathway, which is critical to the homologous recombination DNA repair machinery. An impaired BRCA/FA pathway sensitises tumours to the treatment with DNA cross-linking agents and to PARP inhibitors. The vast majority of inactivating mutations in the BRCA/FA pathway are in the BRCA1 and BRCA2 genes and occur predominantly in high-grade serous cancer. Another member of the BRCA/FA pathway, PALB2 (FANCN), was reported to have been inactivated by DNA methylation in some sporadic ovarian cancers. We therefore sought to investigate the role of PALB2 methylation in high-grade serous ovarian cancers. 

Finding: PALB2 methylation was investigated in 92 high-grade serous ovarian cancer samples using methylation-sensitive high-resolution melting analysis. DNA methylation of PALB2 was not detected in any of the ovarian cancer samples investigated.

Conclusion

Epigenetic silencing by DNA methylation of PALB2 is not a common event in high-grade serous ovarian cancers.

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

Patients’ perceptions on losing access to FPs

Patients’ perceptions 

Conclusion Losing access to FPs evoked a variety of strong feelings among these participants. They engaged in a number of strategies to meet their primary care needs but not without reservations. In a health care system appropriately built on primary health care, the lack of access to FPs is regarded as the loss of a basic right to care. 

The growing pains of cancer survivors: a call for a paradigm of interdisciplinary care | Current Oncology

Current Oncology

"As improved cancer surveillance, more accurate diagnosis, and more efficacious treatment begin to extend life expectancy for numerous patients, the number of cancer survivors will predictably continue to grow into the future1. And as the survivor population increases, new and unique challenges become more apparent.

For example, more than 40% of cancer survivors experience pain after their initial diagnosis2. For those survivors, physical pain is not the only hardship to be faced. They also encounter numerous psychological, social, spiritual, and financial challenges after diagnosis and treatment3. The entire spectrum of pain is now recognized to be more prevalent than earlier thought and unique to each person who has undergone cancer treatment. Particular factors acting in conjunction with the physical causes of pain and contributing to total pain include loss of appetite, loneliness, fatigue, social isolation, existential distress, and family disharmony.....

Skin toxicities caused by targeted therapies - e-Grand Round

Cancer World 

Targeted drugs can result in a variety of skin toxicities that are unpleasant for patients and, if unattended to, can lead them to stop taking their drug as prescribed. Effective teamwork is required to ensure symptoms are identified and managed.

The European School of Oncology presents weekly e-grandrounds which offer participants the chance to discuss a range of cutting-edge issues with leading European experts. One of these is selected for publication in each issue of Cancer World.
In this issue Christine Boers-Doets, from the department of Clinical Oncology at Leiden University Medical Centre in The Netherlands, reviews the occurrence and management of skin toxicities caused by targeted therapies. Annie Young, from the University of Warwick, in Coventry, UK, poses questions arising during the e-grandround live presentation......

Clinical Trials with Pegylated Liposomal Doxorubicin in the Treatment of Ovarian Cancer

open access

"Among the pharmaceutical options available for treatment of ovarian cancer, increasing attention has been progressively focused on pegylated liposomal doxorubicin (PLD), whose unique formulation prolongs the persistence of the drug in the circulation and potentiates intratumor accumulation. Pegylated liposomal doxorubicin (PLD) has become a major component in the routine management of epithelial ovarian cancer. In 1999 it was first approved for platinum-refractory ovarian cancer and then received full approval for platinum-sensitive recurrent disease in 2005. PLD remains an important therapeutic tool in the management of recurrent ovarian cancer in 2012. Recent interest in PLD/carboplatin combination therapy has been the object of phase III trials in platinum-sensitive and chemonaïve ovarian cancer patients reporting response rates, progressive-free survival, and overall survival similar to other platinum-based combinations, but with a more favorable toxicity profile and convenient dosing schedule. This paper summarizes data clarifying the role of pegylated liposomal doxorubicin (PLD) in ovarian cancer, as well as researches focusing on adding novel targeted drugs to this cytotoxic agent.......

Patient Quality of Life Endpoints in Oncology Trials, Part II - Cancer Network

Patient Quality of Life 

"Today we continue our discussion of symptom management and quality of life outcomes in cancer clinical trials with Bryce B. Reeve, PhD, associate professor in the department of health policy and management and a member of the Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill and Carol M. Moinpour, PhD, full member of the Fred Hutchinson Cancer Research Center, Public Health Sciences Division.
Cancer Network: Professor Moinpour, you mentioned that quality of life endpoints have now been incorporated into SWOG trials. What are the main challenges in incorporating these quality of life or symptom measurement data into clinical trials from both of your experiences?.....

Progression-Free Survival: What Does It Mean for Psychological Well-Being or Quality of Life?

open access
Background

Progression-free survival (PFS) is defined as the time from random assignment in a clinical trial to disease progression or death from any cause. PFS as an outcome is of interest to a variety of disciplines, most especially, for purposes of this project, to oncologists, pharmacologists, trialists, social scientists, and other scientists with interest in designing or interpreting clinical trials. This background section addresses how PFS is used, its role as a surrogate for overall survival (OS), the challenges it presents in obtaining accurate and reproducible measurements, and finally its role as a health outcome.

Conclusion
The objective of this methods project was to address whether PFS is an outcome related to psychological well-being or QOL. There were no studies that directly addressed the question of a causal relationship between knowing PFS status and patient anxiety, depression, or psychological well-being. Due to limitations in their design, the four studies demonstrating an association between PFS and better QOL or disease symptoms were all of poor quality. Hence, there is insufficient evidence to make any conclusions about the association between PFS and QOL or related outcomes. The direct measurement of both PFS and QOL may be a practical and informative alternative when measurement of OS is unfeasible.

"PFS as an OS Surrogate for Specific Cancers
Efforts to establish PFS as a surrogate for OS in oncology trials have had variable results depending on the specific cancer. For example, several studies have shown that PFS is a valid surrogate for OS in colorectal cancer,12-15 and it has been argued that PFS is a reasonable primary endpoint for the disease on its own merit.16, 17 Similar conclusions have been reached about PFS as a surrogate for OS in first-line therapy for ovarian cancer.18-20 Expert panelists at two major workshops agreed, however, that the PFS to OS relationship with regard to ovarian cancer may be different for different patient groups or for first-line compared with second- or third-line therapy.18, 20 Contrary to the relative success of PFS as a surrogate endpoint in first-line treatment of colorectal and ovarian cancer, a strong relationship between PFS and OS has not been demonstrated in studies of metastatic breast cancer.4, 12,.....

Ontario Hospital Association: The fifth estate’s “Rate My Hospital” Earns an “F”

NEWS-04112013-CBC5thestate

The fifth estate’s “Rate My Hospital” Earns an “F” 

The OHA urges patients to discuss hospital care with their medical professionals
On April 10, 2013, OHA President and CEO Pat Campbell issued the following statement regarding the fifth estate’s “Rate My Hospital” project:
“Ontario’s hospitals are the most efficient in Canada, and offer world-class care to 13 million patients every year. We are very concerned about the fifth estate’s ‘Rate My Hospital’ project, specifically, that Canadians will use the flawed information contained in it to make decisions about where and when to receive hospital care without the advice of knowledgeable medical professionals.
We urge every Canadian who believes they need immediate medical care to seek it at their nearest possible hospital, and to always discuss their health care needs fully with their medical professionals.
We were involved with the fifth estate’s producers throughout the development of ‘Rate My Hospital,’ and raised very serious methodological concerns about their basic approach to data collection, their heavy reliance on unverified, self-reported data, and their interpretation of the data. The fifth estate refused to acknowledge these concerns or, it appears, address them in their project. For that reason, we believe that the entire ‘Rate My Hospital’ project, and all of the hospital ratings, are fatally flawed, lack credibility, and should be ignored.
As we stated to the fifth estate’s producers, Ontario’s hospitals embrace transparency and accountability. The vast majority of the feed-in information about Ontario’s hospitals collected during the development of ‘Rate My Hospital’ was already publicly available, and had been for some time. Beyond that, Ontario’s hospitals were the first to launch Hospital Report, which was recognized as the gold-standard in hospital performance reporting, and also www.myhospitalcare.ca, a public, consumer-oriented website which displays more than 50 performance indicators about every hospital in Ontario.
Make no mistake: there is always room for hospitals anywhere – including Ontario – to improve infection control practices, human resources, or anything else. Hospital leaders welcome those questions, because they’re committed to improving patient care.
What’s important is that the resulting discussions be driven by the facts – not anecdote, and not opinion. We find it unfortunate that the fifth estate has missed this opportunity to make a meaningful, data-driven contribution to the ongoing discussion about how to improve the quality of Canada’s hospitals. We urge them to rethink their approach to this project should they want to do it again in the future.”

Prognostic Factors For Stage III Epithelial Ovarian Cancer Treated With Intraperitoneal Chemotherapy: A Gynecologic Oncology Group Study

Abstract

Purchase $39.95

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Highlights

•

Survival for IP chemotherapy patients with no residual disease is unprecedented.

•

Prognostic factors include age, histology, and extent of residual disease.

•

More recurrences occur extraperitoneal for patients treated with IP chemotherapy.

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Objectives

To determine prognostic factors for survival in ovarian cancer patients treated with intraperitoneal (IP) chemotherapy using ancillary data from cooperative group clinical trials.

Methods

Data were collected from 428 patients with stage III ovarian cancer who underwent optimal surgical cytoreduction (< 1 cm) followed by IP paclitaxel/platinum chemotherapy. Primary endpoints were progression free survival (PFS) and overall survival (OS). Potential prognostic variables were included in Cox proportional hazard regression models. Multivariate analysis was conducted to identify independent prognostic factors.

Results

Median PFS was 24.9 months (95% CI, 23.0-29.2) and median OS was 61.8 months (95% CI, 55.5-69.8). Predictors for PFS were histology, surgical stage and residual disease. Age, histology, and residual disease were prognostic for OS. There were no differences in the hazard ratio for death or progression between patients with positive, negative, or unknown lymph node status. For patients receiving IP chemotherapy (n=428), 36% of patients had no residual disease with median PFS of 43.2 months (95% CI 32.5-60.4) and median OS of 110 months (95% CI, 60.0-161.3).

Conclusions

Age, histology, and extent of residual disease were predictors of OS in Stage III patients treated with IP chemotherapy following optimal cytoreduction. Patients with no residual disease following primary surgery that are treated with adjuvant platinum based IP chemotherapy have survival measures that exceed any rates previously seen in this population.