Friday, June 18, 2010
abstract/Cochrane Collaboration review: DNA-repair pathway inhibitors for the treatment of ovarian cancer (PARPs...AZD2281)
Plain language summary
Are DNA repair inhibitors as effective and harmless compared to conventional chemotherapy in the treatment of ovarian cancer?
Ovarian cancer is the sixth commonest cancer in women world-wide and remains a leading cause of death, with an annual incidence of 6.6 cases per 100,000 women and an annual mortality rate of 4.0 deaths per 100,000 women. Most ovarian cancers (90%) are epithelial ovarian cancer and arise from the surface of the ovary. Epithelial ovarian cancer typically occurs in post-menopausal women, with a peak incidence around the age of 60, although it does occur in younger women, often associated with genetic predispositions. The onset of this disease is insidious and 75% of women present with advanced stage disease (stage III or IV) when the 5 year survival is around 30%. Treatment consists of debulking surgery and platinum-based chemotherapy, with or without taxanes. Although initial response to chemotherapy is good, most women will relapse, requiring further chemotherapy treatment and develop cancer that is resistant to chemotherapy.
Conventinal chemotherapy acts on all rapidly dividing cells by damaging DNA. Cancer cells divide very rapidly, which is why chemotherapy works better on cancer cells than normal cells. However, there is no inherent selectivity for normal calls and so rapidly dividing cells, such as gut lining, hair follicles and bone marrow, are also affected, leading to diarrhoea, mouth ulcers, hair loss, anaemia and susceptibility to infections.
All cells are equipped with a number of systems or pathways that repair DNA damage. If cells are unable to repair their DNA, the cell undergoes programmed cell death (apoptosis) in order to prevent an abnormal cell from dividing. Because being able to repair DNA is vital to cell survival, normal cells have more than one DNA-repair pathway, so that if one is lost cells can still repair themselves. Cancer cells often develop defects in these pathways, due to mutations, which may promote development of cancer (e.g. BRCA mutations). However, these same mutations mean that these cancer cells are more susceptible to DNA damage, such as that caused by chemotherapy, than normal cells. Novel therapeutical agents have been developed to inhibit DNA-repair pathways, which makes cells that already have faults in another DNA repair pathway due to a mutation, exquisitely sensitive to DNA damaging chemotherapy agents. The most common target for this type of novel anti-cancer agent are the DNA-repair enzymes called poly (ADP-ribose) polymerases (PARPs). PARPs are a family of related enzymes, which are involved in regulating various cellular processes, including DNA repair, cell death, and inflammation. PARP inhibitors therefore have a potentially wide range of applications.
Our objective was to compare effectiveness and side effects of PARP inhibitors compared to conventional chemotherapy in women with ovarian cancer. The identification of a safe dose of AZD2281 (a PARP inhibitor) has been found by small non randomised trials, with encouraging results. For ovarian cancer, there are currently two ongoing RCTs, but outcome data are not yet available. Results of these trials are awaited to determine if DNA repair inhibitors have a role in addition to conventional chemotherapy in the treatment of ovarian cancer.
OCATS - Ovarian Cancer Awareness & Treatment in Saskatchewan - ovarian cancer survivors meet again this year
August 14 & 15, 2010 – International Gathering of Ovarian Cancer Women Supporting Each Other (ACOR), Regina, SK, Canada.
This event will include a free BBQ Dinner for patients and their partners on the 14th – to register for this contact Darlene at 306-775-1848 or info@ocats.ca
A luncheon for women only on the 15th out at Homestead Hall - a Prairie Girl Experience!
Golfing on the 15th for the guys at the awesome Deer Valley Golf Resort A Block of Rooms have been set aside at the "Regina Inn, for more info or to register under “OCATS Aug 2010”
For more info call Darlene at 306-775-1848 or info@ocats.ca
Abstract/full free access | Increased androgen receptor expression in serous carcinoma of the ovary is associated with an improved survival
Background
Altered androgen hormone homeostasis and androgen receptor (AR) activity have been implicated in ovarian carcinogenesis but the relationship between AR expression in ovarian cancer and clinical outcome remains unclear.Conclusions
AR expression is considerably reduced in EOC as compared to fallopian tubes, and in EOC of the serous subtype, high AR expression is a favourable prognostic factor. These results indicate that assessment of AR expression might be of value for treatment stratification of EOC patients with serous ovarian carcinoma."While several immunohistochemistry (IHC)-based studies have confirmed widespread AR (androgen receptor)expression in EOC, data describing it as a prognostic biomarker are relatively sparse. One study describing a large series of tumors (n=322), found no association between AR protein expression and clinical outcome, however individual histological subtypes were not examined. Increased levels of AR mRNA
have been described in cells from normal ovarian surface epithelium as compared to ovarian cancer cells, the majority of which were derived from serous tumors. We are, however, unaware of any studies describing AR expression in fallopian tubes, from which a substantial but not yet not fully appreciated proportion of serous ovarian carcinomas are thought to arise.."
UK - Cancer research centre launched - Herald Scotland | News | Health
"A new centre which is set to become one of the UK’s leading research facilities on ovarian, bowel and breast cancer opens in Edinburgh today.
The Edinburgh Cancer Research UK Centre is part of a country-wide network of centres that are run under the auspices of Cancer Research UK.
Their aim is to prevent duplication of research and bring together world class laboratory researchers with doctors to provide the best possible results for cancer patients in the future.
Edinburgh is known for its globally renowned research on genetics and the biology of cancer. The centre aims to become a world centre for developing treatments tailor-made for individual patients.
Researchers will also look at the problem of cancer cells spreading, and developing drug resistance.
David Cameron, professor of oncology and head of NHS Lothian Cancer Services, is the clinical director of the new centre. He said: “This is a very exciting development for cancer patients and for research in Scotland......"
Regulator to reject ovarian cancer treatment approve Trabectedin (Yondelis)
18th June 2010 - The health regulator, "The National Institute for Health and Clinical Excellence (NICE), says a new treatment for ovarian cancer is not recommended for the NHS because the manufacturer did not submit sufficient evidence that the medication benefits patients more than the most widely-used treatments.
NICE is appraising trabectedin (Yondelis) in combination with pegylated liposomal doxorubicin (PLDH) for the treatment of relapsed ovarian cancer that is sensitive to platinum-based therapies.
Its independent advisory found that the evidence submitted by the manufacturer was not robust because it did not compare trabectedin against a current ‘gold-standard’ treatment for relapsed ovarian cancer: paclitaxel in combination with platinum-based chemotherapy. This meant NICE couldn’t confirm whether or not the treatment extends patients’ lives for longer than one of the more effective and commonly-used treatments...."
Thursday, June 17, 2010
Framework Needed for Research Ethics Review During Public Health Emergencies
Note: discussion with particular reference to SARS (2003).
blog author's opinion: the most interesting/important comment in the article might be the following, as below. The larger question is the resulting action.
"Provide guidance and education on the important differences between public health research and practice to foster consistency in application of the differences and on how to recognize when projects proposed during emergencies cross the line from practice to research."
free full access: Familial colorectal cancer risk: ESMO Clinical Practice Guidelines — Ann Oncol
Note: I believe that registration (free) is required to view this article
Lynch syndrome
prevalence and penetrance of mismatch-repair gene mutations
Lynch syndrome is the most common hereditary colorectal cancer (CRC) syndrome and it accounts for ∼1%–3% of all CRC burden. The syndrome is transmitted with an autosomal dominant pattern and it is associated with mutations in the mismatch repair (MMR) genes, MLH1, MSH2, MSH6 and PMS2. These alterations lead to tumour DNA instability at microsatellites (MSI) and foster inactivating mutations in tumour suppressors containing microsatellites (i.e. TGF-βRII and BAX). Mutations in the MMR genes may lead to loss of expression of the corresponding protein and be detected by immunohistochemistry (IHC) techniques.
Overall, mutation carriers mainly have an increased risk of CRC (lifetime 30%–70%) and endometrial cancer (lifetime 30%–60%). Other extracolonic tumours observed at increased risk (lifetime 5%–15%) are urinary tract, small intestine, ovary, gastric, pancreas, biliary tract, brain and sebaceous gland tumours. A genotype–phenotype correlation has been observed in which MLH1 mutation carriers are at higher risk of young onset CRC cancer, MSH2 at higher risk of extracolonic cancers, MSH6 at increased risk of endometrial cancer and PMS2 carriers show a lower lifetime absolute risk of CRC and endometrial cancer (15%–20%) compared with other mutation carriers.
The name Turcot syndrome refers to patients with MMR gene mutations and brain tumours, and the name Muir–Torre syndrome to patients with cutaneous gland tumours (keratoacanthomas, sebaceous adenomas or adenocarcinomas)......cont'd
The breast cancer “plunge” after initial publication of the WHI results: An alternative explanation
Abstract
From
2002 to 2003, the breast cancer incidence in the United States, as
reported by the National Cancer Institute's Surveillance Epidemiology
and End Results (SEER 9) database, appeared to decrease by 6.7%. This
phenomenon has been attributed to a reduction in the use of menopausal
hormone therapies after the initial publication of the Women's Health
Initiative (WHI) study results in July of 2002.
However, attempts to
draw a causal association between the use of menopausal hormone
therapies and the incidence of breast cancer have not accounted for the
facts that prescriptions of estrogen-plus-progestin menopausal
therapies, which are associated with increased rates of breast cancer,
fell by 53% from 2002 to 2003, while prescriptions of estrogen-only
therapies fell by only 27%. To address this issue,...
Intrauterine device use among women with ovarian cancer: a systematic review
Results
Of the 250 articles identified by our search strategy, none provided evidence (direct or indirect) regarding the safety of IUD use among women with ovarian cancer.
Conclusions
No evidence on the safety of IUD use among women with ovarian cancer was identified. While there are some theoretical concerns that IUD use might affect monitoring of disease progression of sex cord-stromal (non-epithelial ovarian) tumors, or increase risk of pelvic infection or vaginal bleeding among women undergoing chemotherapy, we did not find any data to suggest that IUD use would lead to worsening of primary ovarian cancer.
Cardiovascular Safety of VEGF-Targeting Therapies: Current Evidence and Handling Strategies -- Girardi et al., 10.1634/theoncologist.2009-0235 -- The Oncologist
Abstract
Treatment with the angiogenesis inhibitors bevacizumab, sunitinib, and sorafenib as single agents or in combination with conventional chemotherapy is becoming a cornerstone of modern anticancer therapy. However, the potential toxicity of these drugs, mainly to the cardiovascular system, is still being investigated. Patient assessment at baseline, of crucial importance in candidates for treatment, involves the evaluation of risk factors and screening for past or present cardiovascular disease. Strict monitoring of treatment-related adverse effects must be conducted in order to allow the early detection of cardiovascular toxicities and their prompt medication. In the present paper, the most frequent cardiovascular toxicities and their underlying mechanisms are investigated, with a view to providing indications for effective patient management.
free full access: Preferred and actual participation roles during health care decision making in persons with cancer: a systematic review University
Note: gynecologic cancers included as one cancer (not broken down in chart)
table 1: Preferred role versus actual or perceived role in treatment decision making (list of studies)
table 2: Summary range of patients’ preferred role versus actual role by cancer type (click on 'read more')
...........................................................................................................................
conclusions:
The descriptive nature of the studies
included in this review makes it very difficult to calculate the exact
difference between
preferred and actual roles in decision making;
hence, the authors report a summary range. Nevertheless, despite the use
of
a summary range, it is still quite clear that there
is a limited concordance between preferred and actual roles in decision
making. This limited concordance between patients’
preferred and actual roles assumed during decision making has indicated
that clinicians need to raise their sensitivity
regarding patient's participation in health care decisions. Given the
variability
and dynamic nature of patients’ role preferences,
an individual assessment should be carried out during the entire course
of treatment planning, particularly each time a
critical treatment decision is about to be made. There is a need for
clinicians
to improve their communication skills to promote a
patient's willingness to share his/her needs and desires. Innovative
intervention
studies that can improve matching of patient's
preferred and actual roles during decision making are warranted as are
studies
that examine clinicians’ views on patient
participation in decision making. Research on how patient- and
clinician-related
characteristics affect treatment decisions (e.g.
age, gender, race/ethnicity, education) is also needed to determine
those
factors that affect the actualization of patients’
preferred role.
free full text: Non-epithelial ovarian cancer: ESMO Clinical Recommendations for diagnosis, treatment and follow-up
Note: the papers from ESMO (ovarian cancer) requires registration/access is free 1) Classification of germ cell ovarian tumors 2) Classification of sex cord stromal ovarian tumors "This set of recommendations applies to invasive epithelial ovarian carcinoma; the management of tumors of low malignant potential (‘borderline’) is not covered here."
full free access: Newly and relapsed epithelial ovarian carcinoma: ESMO Clinical Recommendations
Approved by the ESMO Guidelines Working Group: April 2002, last update October 2008. This publication supercedes the previously published version—Ann Oncol 2008; 19 (Suppl 2): ii14–ii16.
free full access: Diabetes and Cancer: A Consensus Report -- A Cancer Journal for Clinicians
"Because specific antihyperglycemic medications are associated with cancer risk factors, confounding by unmeasured or incompletely measured risk factors may explain at least in part the previously reported associations between medications and cancer. To our knowledge, few studies to date have examined the risk associated with the dose, duration, or recency of medication use, which might inform the biologic plausibility of observed associations. Many agents that affect carcinogenesis have long latencies or require a minimum exposure level, and the risk associated with some agents may return to baseline after the exposure has been terminated for a period of time. Some diabetes medications have only recently come on the market (eg, TZDs, insulin analogs, and incretin-based therapies), and therefore, studies of these agents will only assess the cancer risk associated with relatively short-term use.
It is unlikely that the effect of diabetes therapies on cancer risk and progression, particularly at specific cancer sites, will be fully addressed with randomized controlled clinical trials, due to both cost and follow-up time limitations.
free full access: Angiogenesis Inhibitors: Current Strategies and Future Prospects -- A Cancer Journal for Clinicians
Note: references ovarian cancer
Subject: Q&A with Hannah Ortiz, gynecologic oncologist in Long Island, New York (media interview)
"Is there a shortage of gynecologists on the North Fork?
I am the only gynecologist who has an office [full time] on the North Fork. And I'm the only gynecologist who has had a permanent office on the North Fork in 25 years. I'm not talking specialty. I'm talking general gyn. Riverhead is the town where the North and South forks separate. There are two ob-gyn practices in Riverhead. And there are several on the South Fork of Long Island, East Hampton, Southampton and Hampton Bays. The only [full-time] gyn practice on the North Fork driving east is mine."
New Guidelines Emphasize the Need for Cancer Patients to Exercise
Note: "some gynecologic cancers"/talks briefly about "changes in neuropathy"/treatments etc
" Research Gaps Remain
The panel found that there is consistent evidence that exercise training can lead to improvements in aerobic fitness, muscular strength, quality of life, and fatigue in breast, prostate, and hematologic cancer patients and survivors, but that the data for colon and gynecologic cancers are still too limited to lead to conclusions.
Multiple research gaps remain in this field, the panel notes. These include a need for greater specificity with regard to the dose-response effects of specific modes of exercise training on specific end points and within a broader range of populations, such as survivors of colon and gynecologic cancers.
They also urge fitness trainers who work with cancer survivors to learn as much as possible about the specifics of the cancer diagnosis and treatment to make informed safe choices with regard to exercise testing and prescription.
Cancer diagnosis and treatment effects numerous body systems that are required for and affected by exercise training, they conclude, and "because cancer treatments are increasingly customized according to specific tumor characteristics, fitness professionals may benefit from contacting the medical treatment team for more precise information regarding the treatments received.""
EvidenceUpdates/Commentary: Estrogen alone in postmenopausal women and breast cancer detection by means of mammography and breast biopsy
Note: postmenopausal women/followup from WHI study
Wednesday, June 16, 2010
UK News | Ovarian cancer study offers vital clues for new therapies
Note: interesting article
"A University of Edinburgh study suggests that ovarian cancer patients whose tumours spread to the solid organs such as the liver and lungs should be tested for the faulty genes - BRCA1 and BRCA2 - to ensure they are given the most appropriate treatment...."
early research: Blood relations: New study explores early detection of ovarian cancer
Note: in research (single chain variable fragments or scFvs)
full free access: Biomarkers in Medicine - The dire need to develop a clinically validated screening method for the detection of early-stage ovarian
Note: I remember the LPA very well (breakthrough screening test for ovarian cancer and the resulting media hype extraordinaire)
Key Excerpts:
Multiple initiatives have been undertaken to discover strategies that detect and diagnose early-stage EOC, including the search for novel serum biomarkers and the development of new technologies, such as contrast-enhanced ultrasonography, with a number of them demonstrating hopeful results. The ideal screening test for ovarian cancer would be a simple measurement of biomolecules in bodily fluids, such as blood, serum or urine, whose absolute concentrations could differentiate cancer from noncancer and be organ specific. In the last decade, insights into the EOC microenvironment, as well as technological advances, such as microarrays and proteomics, have triggered the discovery of hundreds of potential clinically valuable biomarkers:
▪ Lysophosphatidic acid (LPA) is a phospholipid derivative consisting of a glycerol backbone, a single fatty acid chain and a free phosphate group. LPA has a variety of isoforms depending on fatty acid-chain variability at the sn-1 position. LPA was found to be elevated in the serum, plasma and malignant effusions of women with ovarian cancer and has known functions in cell proliferation, invasion and angiogenesis [3]. This molecule initially became of interest in 1998 for its reported high sensitivity and specificity to detect early-stage ovarian cancer [3]; however, its utility as a screening biomarker has been limited owing to the difficulty of isolating and detecting the different isoforms in patients’ serum and its specificity for ovarian cancer;
▪ Human epididymal protein (HE)4 is a relatively new biomarker used to monitor disease recurrence and disease progression in patients with ovarian cancer. It is the product of the WFDC2 (HE4) gene, which is overexpressed in ovarian cancer. HE4 has exhibited increased sensitivity to detect stage I disease [4] and has demonstrated promise as a sensitive and specific biomarker when combined with CA125 and other molecules [5]; although, more studies remain to be done to warrant its use as a biomarker for the detection of early-stage EOC;
▪ Osteopontin (OPN) is a glycoprotein involved in cell adhesion, inflammation and tumorigenesis, with elevated levels seen in ovarian cancer [6]. Similar to HE4, OPN has been used in combination assays to identify ovarian cancer [7]; however, OPN is also elevated in other cancers and benign conditions, limiting its specificity to be used as an ovarian cancer biomarker;
▪ Kallikreins (KLKs) are serine proteases that function in cell growth, angiogenesis and invasion. KLKs are elevated in patient serum with ovarian cancer. KLK8 was reported to be associated with early disease, while KLK5, -6, -10 and -13 have been combined with CA125 to improve the accuracy of ovarian cancer detection [8,9];
▪ Claudins are components of tight junctions that create selective barriers and maintain cell polarity. Multiple claudins have been found to be elevated in ovarian cancer; however, their specificity has yet to be determined and verified [10].
..................
Of particular note, traditional genetic pedigree analysis of ovarian cancer patients may provide information to help identify high-risk populations; for example, inherited BRCA1 and -2 mutations increase the risk for women to develop ovarian and/or breast cancer [12]. In addition, molecular profiling at the epigenetic level, such as miRNA profiling, may allow for the identification of novel biomarkers for early detection of ovarian cancer, given that these epigenetic changes might be detectable before the development of the physical tumor.
................
Despite these advances, at present, no clinically validated screening protocol for the detection of early-stage EOC exists. The discovery of novel biomarkers relies on obtaining a better understanding of the initiation and progression of EOC. Clinical validation and implementation of biomarkers will also benefit from advancements in new molecular and imaging technologies as patient care is optimized. Fortunately, hundreds of biomarkers have been identified; however, their clinical utility remains to be determined. In addition, the enhanced imaging capabilities of the ovary by ultrasound are providing practitioners with the ability to more accurately and precisely identify changes specific to the newly transformed ovary. The combination of these two modalities, biomarker panels and biologically based imaging may be the future. Therefore, we must forge ahead to develop a validated early-detection protocol that will not only decrease the number of advanced-stage diagnoses and deaths attributed to ovarian cancer but, most importantly, positively impact the future of women’s healthcare.
Ovarian Low Malignant Potential Tumors (borderline ovarian tumors) Treatment, Masonic Cancer Center, University of Minnesota
Note: also commonly referred to as "LMP"
ENDO (Endocrine) 2010 News Conference - Menopause/Hormones/Aging Women
Monday, June 21
Endocrine-Disrupting Chemicals: Evidence of Impact (9:30 a.m. PDT): Frontier research on the impact of exposure to endocrine-disrupting chemicals.
Menopause: Hormones and the Aging Woman (1:30 p.m. PDT): Release of the Society’s scientific statement on postmenopausal hormone therapy and breaking research on risks associated with menopause and treatment of menopausal symptoms.
PharmaLive: Curis / GDC-0449 [phase 11 trial results to follow
Note: excerpt - Avastin + chemo
"Genentech and Roche are also conducting a randomized double-blind placebo-controlled Phase II trial in advanced ovarian cancer in a maintenance setting, which is evaluating the ability of GDC-0449 to slow the time to recurrence of cancer in patients whose disease is in complete remission, by impeding the residual cancer cells' ability to grow. Roche has indicated that results from this study are expected during the second half of 2010."
A prime example of the problem with some TV physician-"journalists" - Gary Schwitzer's HealthNewsReview Blog (ASCO/ovarian cancer/Avastin) + my response
Note: my response:
"In our own ovarian cancer patient communities and over the long term, as survivours/family caregivers, many of us have learned to question media articles and abstracts. The SGO published a statement regarding the GOG 218 study shortly after the media events.
In addition, on June 5th in Chicago on a separate ovarian cancer seminar the issue of the new finding of GOG 218 were discussed. The over-riding bottom line is that Avastin is not the panacea for all that ails ovarian cancer women and should be used very selectively. On which patients is of primary interest (obviously).
The issue at stake for ovarian cancer women is that no new treatments in the past 2 decades have shown any improvements over the standard and current first line therapy of Taxol and Carboplatin.
No matter how bad it gets (QOL) and it does get very 'bad', ovarian cancer women want to live and will suffer much to do so. We need to understand this mindset while at the same time considering first most patient safety and always acknowledging the 'hype'.
There is a duty for all those who care for ovarian cancer women to be informed.
Twitter, blogs, facebook and social media help also to educate patients on these issues - we hope."
(The Patient Factor) - Patient Safety (Canada) - patient advocacy/system - illustrated by Ed Mendoza's journey on behalf and for his wife
"....In February 2008 he sat on the steering committee of PFPSC and helped them develop a charter for the organization. Three months later the amicable relationship between Ed and the WRHA ended abruptly when they informed him that a restructuring of their Patient Advisory Council meant that he could no longer be a member. Ed was extremely disappointed but undeterred in his patient safety efforts. In September 2008 the CPSI, the funding body for PFPSC, invited him to speak at their Canadian Patient Safety Officer Course. One month later he received a call from PFPSC dismissing him from the group. In January 2009 he received an official letter outlining the reason for his expulsion. The letter makes reference to his speaking engagement and the message contained in his information booklet...."
Osteopontin is a new target molecule for ovarian clear cell carcinoma therapy
Abstract (in research)
"Recent studies have demonstrated overexpression of osteopontin (OPN) in ovarian clear cell carcinoma.
Here, we revealed the role of OPN in invasiveness in ovarian clear cell carcinoma......Immunofluorescence analysis revealed statistically significant differences among the histological groups, and ovarian clear cell carcinoma expressed a strong OPN signal....Simvastatin significantly reduced expression of OPN and the integrins, and decreased ECM invasion. RNA interference also suppressed ECM invasion....We thus conclude that OPN regulation could have a crucial role in ovarian clear cell carcinoma therapy."
Is this patient empowerment or something else? - EmpowHER.com
Note: including my comment (see article); old and outstanding issues/dialogue anyone?
".....Last weekend I was part of a group working on a conference for cancer patients. There were no patients listed as conference speakers ........."
The primary care physician role in cancer genetics: a qualitative study of patient experience Family Practice
Abstract
Background. Increased availability of genetic testing is changing the primary care role in cancer genetics. The perspective of primary care physicians (PCPs) regarding their role in support of genetic testing has been explored, but little is known about the expectations of patients or the PCP role once genetic test results are received.
Methods. Two sets of open-ended semi-structured interviews were completed with patients (N = 25) in a cancer genetic programme in Ontario, Canada, within 4 months of receiving genetic test results and 1 year later; written reports of test results were collected.
Results. Patients expected PCPs to play a role in referral for genetic testing; they hoped that PCPs would have sufficient knowledge to appreciate familial risk and supportive attitudes towards genetic testing. Patients had more difficulty in identifying a PCP role following receipt of genetic test results; cancer patients in particular emphasized this as a role for cancer specialists. Still, some patients anticipated an ongoing PCP role comprising risk-appropriate surveillance or reassurance, especially as specialist care diminished. These expectations were complicated by occasional confusion regarding the ongoing care appropriate to genetic test results.
Conclusions. The potential PCP role in cancer genetics is quite broad. Patients expect PCPs to play a role in risk identification and genetics referral. In addition, some patients anticipated an ongoing role for their PCPs after receiving genetic test results. Sustained efforts will be needed to support PCPs in this expansive role if best use is to be made of investments in cancer genetic services.
Tuesday, June 15, 2010
NEJM -- The Path to Personalized Medicine (U.S.)
"...In February, the NIH and the FDA announced a new collaboration on regulatory and translational science to accelerate the translation of research into medical products and therapies; this effort includes a joint funding opportunity for regulatory science. Working with academic experts, companies, doctors, patients, and the public, we intend to help make personalized medicine a reality. A recent example of this collaboration is an effort to identify new investigational agents to which certain tumors, identified by their genetic signatures, are responsive.
Real progress will come when clinically beneficial new products and approaches are incorporated into clinical practice. As the field advances, we expect to see more efficient clinical trials based on a more thorough understanding of the genetic basis of disease. We also anticipate that some previously failed medications will be recognized as safe and effective and will be approved for subgroups of patients with specific genetic markers.
When the federal government created the national highway system, it did not tell people where to drive — it built the roads and set the standards for safety. Those investments supported a revolution in transportation, commerce, and personal mobility. We are now building a national highway system for personalized medicine, with substantial investments in infrastructure and standards. We look forward to doctors' and patients' navigating these roads to better outcomes and better health."
ASCO: Continuity of care for cancer patients at the end of life (EoL). -- Bascioni et al. 28 (15): 6145 -- ASCO Meeting Abstracts
Conclusion: Continuity of care at the EoL is a priority issue for the families of cancer pts. The daily routine of palliative care and hospice facilities should involve the oncologist to improve the experience of care. Patients' families expect a commitment by the oncologist in bereavement activities.
Commentary: June 14th: Personalizing Therapy for Ovarian Cancer: BRCAness and Beyond -- Bast and Mills, 10.1200/JCO.2010.28.5791 -- Journal of Clinical Oncology
Note: links directly to pdf article/overview of ovarian cancer treatments including PARPs, Avastin, Tamoxifen, AZ6244..
"If we are to progress at an optimal pace, accrual of a larger fraction of patients to clinical trials will be essential, requiring referral of ovarian cancer patients to major centers at first recurrence of their disease."
Merger of Cancer Australia and NBOCC will unify efforts to address increasing cancer rates
15 June 2010
"The Australian Government’s planned amalgamation of Cancer Australia and the National Breast and Ovarian Cancer Centre (NBOCC) should consolidate efforts to address the nation’s escalating cancer incidence rates, Cancer Council Australia and the Clinical Oncological Society of Australia (COSA) said today (15 June)...."
Society of Gynecologic Oncologists Statement on Use of CA125 in Screening for Ovarian Cancer
press release:
June, 2010
Society of Gynecologic Oncologists Statement on Use of CA125 in Screening for Ovarian Cancer
Results of a multicenter screening trial using calculated algorithms based on age and trends in CA125 levels over time in women without familial risk of developing ovarian cancer have recently been reported at the annual meeting of the American Society of Clinical Oncology. Transvaginal ultrasound (TVUS) was not performed automatically but as indicated by the CA125 algorithm results. This study provides early evidence that incorporating a CA125 algorithm followed by TVUS may be a feasible strategy for screening low-risk women over 50 years of age. The results of this study have been featured in various professional and consumer media outlets, causing physicians and patients to seek guidance regarding the implications.
The Society of Gynecologic Oncologists commends the investigators of this study for contributing valuable data, and eagerly awaits the results of additional larger randomized controlled trials to confirm the usefulness of Risk of Ovarian Cancer Algorithm (ROCA) in screening women without familial risk of ovarian cancer. The positive predictive value noted in the study of 37.5% is superior to what has been reported from prior studies. However, as a screening strategy, that eventually could be applied to the general population, this figure is modest. There remains insufficient evidence to support routine CA125 +/- TVUS screening in low-risk women who are not part of a clinical trial. An additional limitation of this study was the lack of a control, observation-only arm, without which it is difficult to attribute any real benefit to the screening strategy. As with any prospective screening tool or treatment option, the impact of false positive and false negative screening results must be considered and balanced against the potential benefits of true positive and negative results. Finally, while the number of participants who needed more frequent CA125 monitoring, ultrasound, or referral to a specialist appeared small, a complete cost effectiveness analysis of this approach would be critical before adopting any universal screening program.
As specialists in women’s cancer care, gynecologic oncologists offer patients individualized treatment plans. Patients and their physicians are encouraged to discuss the pros and cons of CA125 and TVUS screening and the implications for subsequent treatment and quality of life.
Breakthrough Pain Significant for Many Cancer Patients
Note: this is a good article/registration required (free)
MuGard (oral mucositis - U.S.) Access Pharma Initiates US MuGard Sampling Program with Leading Oncology Groups - MarketWatch
"...Sampling efforts for the company include providing large oncology groups with MuGard kits containing six weeks' worth of MuGard therapy for patients undergoing radiation and chemotherapy. Through these oncology groups, Access Pharma initially will provide 500 patients throughout 20 top metropolitan areas full courses of therapy to protect them from oral mucositis."
p53 autoantibodies as potential detection and prognostic biomarkers in serous ovarian cancer
IMPACT: Although their utility as a preoperative diagnostic biomarker, beyond CA 125 and HE4, is limited, p53-AAb are prognostic for improved overall survival.
Hospice enrollment for terminally ill patients with gynecologic malignancies: Impact on outcomes and interventions
CONCLUSIONS: While retrospective reviews evaluating hospice are challenging, our data suggest no detrimental impact on survival for hospice patients (vs non hospice). Continued evaluation for patients at the end-of-life is necessary in order to optimize resource utilization.
Neurobiological cause of intergroup conflict: 'Bonding hormone' drives aggression towards competing out-groups (altruism)
"The evolution of altruism in intergroup conflict
The research team at the University of Amsterdam, directed by Dr. Carsten de Dreu, wondered why oxytocin would promote altruistic behavior. Whereas classic economic theory has difficulty accounting for altruism, an evolutionary perspective suggests that altruism functions to strengthen one's own group, from which the individual benefits in the long run. Because aggression towards competing out-groups helps one's own group to become relatively stronger, aggression is an indirect form of altruistic, loyal behavior towards one's own group........Charles Darwin already observed that groups whose members are altruistic towards the own group have a greater likelihood to prosper, to survive, and spread...."
First-in-human trial of a poly(ADP-ribose) polymerase (PARP) inhibitor MK-4827 in advanced cancer patients (pts) with antitumor activity in BRCA-deficient and sporadic ovarian cancers (phase 1)
Results: 39 pts (male 10, female 29; median age 58 years; 11 BRCA mutation carriers) were treated...
Conclusions: MK-4827 is well tolerated, blocks PARP and has promising antitumor activity in both BRCA-deficient and sporadic cancers.
Efficacy of lower dose of weekly topotecan in recurrent epithelial ovarian and primary peritoneal cancer resistant to platinum-based therapy
Conclusions: Lower dose of weekly topotecan was well tolerated in patients with platinum-resistant ovarian or peritoneal cancer at first relapse, with a favourable hematologic profile. Moreover, antitumor activity was similar to that reported for the standard dose of weekly regimen.
Associations between age and quality of life in advanced ovarian cancer
Background:
..... Few studies have examined whether age influences advanced ovarian cancer patients' prognostic understanding or quality of life at the time of diagnosis."
Conclusions: EpCAM is highly expressed in primary chemotherapy- resistant ovarian carcinoma cell lines, and these chemotherapy-resistant tumors are highly sensitive to MT201-mediated cytotoxicity in vitro. MT201 may represent a novel, potentially highly effective treatment option for patients harboring chemotherapy-resistant ovarian carcinoma.
Note: EpCAM epithelial cell adhesion molecule (EpCAM); EpCAM gene can be tested either independently or as part of genetic testing - depending on the testing procedure (eg. Lynch Syndrome); study included clear cell ovarian cancer
(Review) Methodologic challenges in assessing patient-reported outcomes among women with relapsed/refractory ovarian cancer - QOL
Note: study of mechanisms in identifying QOL
Conclusions: PRO among women with R/R ( relapsed/refractory)ovarian cancer is limited in quality. More data are needed from R/R ovarian cancer studies to identify not only the most appropriate PRO instruments, but also methodologic strategies necessary to yield useful PRO data
Interleukin-6 as a therapeutic target in advanced ovarian cancer
Note: "Four of the eighteen patients completed 6 months of treatment and this included the partial responder who had continued decreases..."
Nonepithelial ovarian cancer: Outcomes after aggressive treatment with surgery and platinum-based chemotherapy
Conclusions:
In this high-recurrence-risk group of nonepithelial ovarian cancers, aggressive treatment with surgery and platinum- based chemotherapy resulted in excellent survival outcomes.
A KRAS-variant as a biomarker of ovarian cancer risk
Note: KRAS has been studied in colorectal cancer impacting on treatment program/no indication if ovarian cancer/Lynch Syndrome patients were included
Conclusions: These findings strongly support the hypothesis that the KRAS-variant is a genetic marker of an increased risk of developing ovarian cancer, and suggests that the KRAS- variant may be a new biomarker of risk for HBOC families without other known genetic abnormalities. In addition, the KRAS-variant predicts for the most deadly ovarian cancers, which are likely the most important to prevent or catch early.
abstract: A prospective U.S. ovarian cancer screening study using the risk of ovarian cancer algorithm (ROCA)
ASCO (Post-Meeting Edition)
Abstract
5003
Background: There are currently no effective screening tools for the early detection of ovarian cancer in women at average population risk. We evaluated a screening strategy that incorporates change of CA-125 over time and age of the participant to estimate risk of ovarian cancer, referring a small fraction (
2%) of
apparently healthy individuals annually to transvaginal
sonography (TVS). Methods: A single arm, prospective, multicenter screening study enrolled postmenopausal women age 50 to 74 with no significant family history of breast or ovarian cancer. Participants underwent a CA-125 blood test annually. Based on the Risk of Ovarian Cancer Algorithm (ROCA) result, women were triaged to the next annual CA-125 (low risk), repeat CA-125 in 3 months (intermediate risk), or TVS and referral to a gynecologic oncologist (high risk). Based on clinical findings and TVS, the gyn onc made the decision whether to proceed with surgery.
Results: 3238 women participated over an eight year period. The average annual rate of referral to 3 monthly CA125 was 6.8%, and the average annual rate of TVS and gyn onc referral was 0.9%. Cumulatively 85 women (2.6%) received TVS and referral to a gyn onc. Eight women subsequently underwent surgery based on the TVS and referral, with 3 invasive ovarian cancers, 2 borderline ovarian tumors and 3 benign ovarian tumors, providing a positive predictive value of 37.5% (95% CI 8.5%,75.5%).The combined specificity of ROCA followed by TVS for referral to surgery is 99.7% (95% CI 99.5%, 99.9%). The 3 invasive ovarian cancers were high-grade epithelial tumors that were all early stage (two stage 1C and stage IIB). All 3 women with invasive ovarian cancer had at least 3 years with low risk, annual CA-125 values prior to a rising CA-125.
Conclusions: In this prospective, single arm study, the ROCA followed by TVS demonstrated excellent specificity and PPV in a population of U.S. women at average risk for ovarian cancer. As expected, less than 1% of participants annually required a TVS. In addition, the invasive high-grade ovarian cancers that were detected were early stage. This study provides early evidence that ROCA followed by TVS is a feasible strategy for screening women over 50 years of age.
Monday, June 14, 2010
Seth's Blog: Trying to please
"Trying to please
Who is your marketing or your product or your effort trying to please?
Every campaign that I've ever seen fail has failed for precisely the same reason: it pleases the wrong person. Think about it... it wouldn't have launched if it hadn't pleased the boss or the client, right? Pleasing the wrong person meant failure.
The same thing is true on a deeper level in your career choice or what you write or what you say or what you sell or how you sell it: if you are working hard to please the wrong people, you'll fail.
Does that critic or that buyer or that spouse or that girlfriend or that investor really matter as much as you think they do?"
Every campaign that I've ever seen fail has failed for precisely the same reason: it pleases the wrong person. Think about it... it wouldn't have launched if it hadn't pleased the boss or the client, right? Pleasing the wrong person meant failure.
The same thing is true on a deeper level in your career choice or what you write or what you say or what you sell or how you sell it: if you are working hard to please the wrong people, you'll fail.
Does that critic or that buyer or that spouse or that girlfriend or that investor really matter as much as you think they do?"
Evidence That Consumers Are Skeptical About Evidence-Based Health Care -- abstract/free full access
Note: some key excerpts (U.S. research):
"Beliefs And Values Study participants consistently voiced a number of values and beliefs that were at odds with evidence-based approaches." "All Care Meets Minimum Quality Standards: Although focus-group participants could envision a health care provider’s making an occasional mistake, they found it hard to believe that providers could deliver truly substandard care—and certainly not their own providers."
"Behaviors In The Medical Encounter Our survey results indicate that many consumers do not engage in behaviors that could be beneficial to them during medical encounters. More than half of the respondents had never taken notes during a medical appointment (55 percent) or brought online information to discuss with their doctor (60 percent). Almost half had never brought someone to provide support or advocacy (44 percent). In addition, 28 percent of the respondents had never brought questions to ask their doctor (Exhibit 3)."
"Effective communication with and support of consumers is essential to improving the quality of health care and containing health care costs. Clearly, consumers will revolt if evidence-based efforts are perceived as rationing or as a way to deny them needed treatment. Policy makers, employers, health plans, providers, and researchers will thus need to translate evidence-based health care into accessible concepts and concrete activities that support and motivate consumers. A necessary condition for effective communication, after all, is to start where your audience is—even if that is not where you hoped or expected it to be."
Dr William Li: Can we eat to starve cancer? (anti-angiogenesis) | Video on TED.com (20 minutes video/text - full access)
Note: this video/text was brought to my attention through the Cochrane Collaboration's Consumer Network; references Dr Folkman (cancer without disease), Avastin,food/diet eg. food as drugs research
Sunday, June 13, 2010
abstract/free full text access: Primary peritoneal and ovarian cancers: an epidemiological comparative analysis
Note: click on 'pdf' for access the the full paper; some interesting points regarding talc use, oral contraceptives, number of pregnancies....
Saturday, June 12, 2010
press release:- Correlogic Systems Obtains CE Mark for OvaCheck®
| Correlogic Systems Obtains CE Mark for OvaCheck® |  |  |  |
| Saturday, 12 June 2010 | |
| "Correlogic Systems, Inc. announced today that OvaCheck, the company's blood test for the detection of epithelial ovarian cancer, has fulfilled European Union regulatory requirements (CE marking) for distribution and sale of the test. The path is now cleared for the test to be made available to patients in Europe through their physicians...." |
ASCO abstract: Association of Lynch syndrome and risk of invasive cervical cancer.
Abstract:
Background: Lynch syndrome, a hereditary cancer syndrome characterized by germline mutations in mismatch repair (MMR) genes, is associated with an elevated lifetime risk of cancer development, predominantly endometrial, colorectal and ovarian. To date, no increased risk of cervical cancer for mutation carriers has been reported.
Oral contraceptive use and breast or ovarian cancer risk in BRCA1/2 carriers: A meta-analysis
CONCLUSIONS: OC users carrying an ascertained BRCA1/2 mutation have a reduced risk of ovarian cancer, proportional to the duration of use. There is no evidence that recent OC formulations increase breast cancer risk in carriers
Menopausal hormone therapy and risk of colorectal cancer in the European prospective investigation into cancer and nutrition
"Our results show no significant association of estrogen-only or estrogen plus progestin therapy with colorectal cancer risk."
Avastin, Cancer Drug, Can Cause Kidney Damage - ABC News + patient response/ovarian cancer (proteinuria)
"........The manifestation of proteinuria, even significant proteinuria with therapy, was seen in those pilot studies," said Dr. Bryan Becker, president of the National Kidney Foundation, who is not affiliated with the group that carried out the current study.
However, some doctors said the incidence of proteinuria with the treatment is not a cause for alarm.
"The 2 to 3 percent that have proteinuria is minor," said Dr. Otis Brawley, the American Cancer Society's chief medical and scientific officer, who likewise had no involvement with this research.
It also doesn't concern 46-year-old Julie Del Giorno, a Pennsylvania woman who took Avastin to treat her ovarian cancer as part of a clinical trial last year.
Luckily, she now has no signs of cancer left.
"I'm doing really well. Everything's been fine -- my CT scans have been normal," she said.
After reading about the side effects of Avastin and consulting with her doctor, she decided to give it a try.
"There are always risks involved, and I had trust in the doctors I was working with that it was a good option," she said"....cont'd
Friday, June 11, 2010
ASCO Annual Meeting: Ovarian Cancer: Some Hope in the Quest for an Effective Screening Method
Note: "The prospective study of 3,238 postmenopausal women aged 50 to 74 with no significant family history of breast or ovarian cancer, enrolled over a course of nine years."
CHICAGO—In the continuing quest for an effective screening method to detect ovarian cancer at an early stage, a new approach using an algorithm has shown promise in early testing as reported here at the ASCO Annual Meeting and featured beforehand in a teleconference by the society.
online: NCCS What Do You Wish You Had Known? (U.S.)
What Do You Wish You Had Known?
Most cancer survivors in the U.S. don’t have a cancer treatment plan, treatment summary, or follow-up survivorship care plan. So it’s no surprise, they and their doctors don’t always know what signs and symptoms of long-term and late-term effects to look for or how choices they made at the beginning of treatment might affect their well-being down the road.
What was your experience? Did you have to go back to your doctor again and again to demand a chest x-ray for a cough that was dismissed as allergies? Did your doctor tell you that you’d need bone density scans ahead of time to ward off chemo-related bone loss? Did you sail through treatment only to be hit by a wave of depression after the fact?
Please help us to collect stories from everyone – survivors, caregivers, and providers – across all 50 states, to illustrate what surviving cancer looks like today. Please share a short note about how knowing what to expect ahead of time – or not knowing at all – has affected your health and well-being.
http://www.canceradvocacy.org/take-action/share-your-story.html
Exploring the Interface Between Cancer and Psychiatry - Cancer Network
"As a psychiatrist who has cancer, I have developed a deep understanding of the ways in which our training can help us help patients who find themselves forced to deal with the complicated emotional aspects that accompany this disease. My hope is that my insights will help psychiatrists as they wrestle with the problems that plague their patients who are coping with this difficult disease....."
An update of controlled physical activity trials in cancer survivors: a systematic review and meta-analysis
Conclusions
Current evidence suggests many health benefits from physical activity during and post cancer treatments. Additional studies are needed in cancer diagnoses other than breast and with a focus on survivors in greatest need of improvements for the health outcomes of interest.
A Mechanism Behind Negative Tumor Suppressor Gene Function Identified - p53
Note: the p53 gene has been studied extensively for decades including p53 vaccines, hopefully new research will move research on p53 quickly as its implications in cancer will have a great impact
2010 Institute for Continuing Healthcare Education - Ovarian Cancer Screening and Management to Improve Patient Survival
OVERVIEW
Ovarian cancer is the leading cause of death from gynecologic malignancy and the fifth leading cause of cancer‐related death among women in the United States. The high mortality rate associated with ovarian cancer is due in part to the lack of effective screening strategies to detect the disease in early stages (I or II) when the cancer is confined to the ovary. Since symptoms associated with ovarian cancer are typically nonspecific, a clinical diagnosis is difficult to make until the disease has advanced. The Institute for Continuing Healthcare Education has identified a number of areas related to the screening, diagnosis, and treatment of ovarian cancer where education is vital in order to address the need for improvement in professional care.
PROGRAM DESCRIPTION
In this Webcast, the faculty members will present up-to-date, relevant information on screening guidelines, referral procedures, and therapies for ovarian cancer. As a learning reinforcement, individuals who complete this activity will be able to request a certified monograph with two case studies pertaining to the treatment strategies discussed within the Webcast.
INSTRUCTIONS FOR OBTAINING CME/CE CREDIT
There are no fees or prerequisites for participating in and receiving CME/CE credit for this online educational activity.
Thursday, June 10, 2010
Compassion Fatigue: What Is It? Why Does It Matter? Recognizing the Symptoms, Acknowledging the Impact (healthcare professionals)
Compassion Fatigue: What Is It? Why Does It Matter? Recognizing the Symptoms, Acknowledging the Impact, Developing the Tools to Prevent Compassion Fatigue, and Strengthen the Professional Already Suffering From the Effects
Cancer Symptom Clusters: Old Concept But New Data -- American Journal of Hospice and Palliative Medicine
Note: there are other blog postings regarding symptom clusters (ie; certain symptoms go together eg depression, fatigue etc...) "Symptom clusters may help in cancer diagnosis, symptom management, and prognostication. However, the cluster method, reliability, and validity need to be established before assessment or treatment guidelines are established. Symptom clusters require further research before becoming part of routine medical symptom assessment and management."
abstract: (Avastin) Bevacizumab Increases Risk for Severe Proteinuria in Cancer Patients
Note: one very good caution when undergoing investigational drugs
"Treatment with the chemotherapeutic agent bevacizumab, a humanized mAb that neutralizes vascular endothelial growth factor, can lead to proteinuria and renal damage. The risk factors and clinical outcomes of renal adverse events are not well understood.
We performed a systematic review and meta-analysis of published randomized, controlled trials to assess the overall risk for severe proteinuria with bevacizumab.
We analyzed data from 16 studies comprising 12,268 patients with a variety of tumors. The incidence of high-grade (grade 3 or 4) proteinuria with bevacizumab was 2.2% (95% confidence interval [CI] 1.2 to 4.3%). Compared with chemotherapy alone, bevacizumab combined with chemotherapy significantly increased the risk for high-grade proteinuria (relative risk 4.79; 95% CI 2.71 to 8.46) and nephrotic syndrome (relative risk 7.78; 95% CI 1.80 to 33.62); higher dosages of bevacizumab associated with increased risk for proteinuria.
Regarding tumor type, renal cell carcinoma associated with the highest risk (cumulative incidence 10.2%).
We did not detect a significant difference between platinum- and non–platinum-based concurrent chemotherapy with regard to risk for high-grade proteinuria (P = 0.39).
In conclusion, the addition of bevacizumab to chemotherapy significantly increases the risk for high-grade proteinuria and nephrotic syndrome."
IU-OSU center gets $9 million more for cancer epigenetics: IU News Room: Indiana University (includes ovarian cancer)
"Over the next five years, Nephew said the OSU/IU-led team will study epigenetic changes in prostate, breast, and ovarian cancer cells that cause resistance to hormonal therapy or traditional chemotherapy. Nephew said a major objective is to identify a panel of epigenetic biomarkers for predicting responsiveness to anti-hormone treatments and chemotherapies in cancer patients."
ASCO Conference Summary: Why it’s Important to You | Ovarian Cancer National Alliance
Note: recap of pertinent ovarian cancer topics from ASCO
Search by topic:
ASCO: (Farletuzumab) Antibody Shows Promise in Ovarian Cancer
"The phase II clinical trial evaluated responses in 44 ovarian cancer patients in their first relapse period, who received either farletuzumab as a single agent or in combination with carboplatin and a taxane..."cont'd
ASCO: Drug May Reactivate Chemo Effect in Ovarian CA - Olaparib (PARP)
"Chemotherapy resulted in an overall response rate of 42% in this heavily pretreated patient population, including a 55% response rate for carboplatin and/or a taxane," said Ang. "If these results are confirmed in a larger patient population, they could remain an option for these patients, even if they have demonstrated prior resistance."
The Gastrointestinal Phenotype of Germline Biallelic Mismatch Repair Gene Mutations (Lynch Syndrome)
Abstract
OBJECTIVES:A novel cancer syndrome associated with biallelic mismatch repair (MMR) mutations has been described recently. Patients presenting with childhood-onset gastrointestinal (GI) cancers may carry biallelic MMR mutations and have a distinct phenotype from classic Lynch syndrome. The aim of this study was to characterize patients with GI small bowel and/or colorectal cancers (CRCs) who have germline biallelic MMR mutations.
METHODS:A search of a Canadian GI cancer registry and literature review to identify patients with biallelic MMR was conducted.
RESULTS:The database identified 237 patients with intestinal cancer diagnosed before the age of 35 years. Five (2.1%) patients had biallelic MMR mutations. Overall, 32 individuals, from 29 families, with biallelic MMR gene mutations and GI cancers were identified by the registry and literature review. Among the 29 patients with CRCs, the mean age of first cancer diagnosis was 16.4 years (range: 5-28).
Risk of endometrial cancer for women diagnosed with HNPCC-related colorectal carcinoma
Note: this issue is important as early-age diagnoses in Lynch Syndrome is common
"Approximately one quarter of women diagnosed with Lynch syndrome-associated CRC (colorectal cancer) developed EC within 10 years. This supports the sentinel cancer concept and suggests that active and early management is important for these women."
Preliminary study of neuroendocrine differentiation and its mechanism in ovarian epithelial tumors
Note: abstract is in English/full free pdf file is in chinese
Abstract
OBJECTIVE: To investigate neuroendocrine differentiation and its mechanism in ovarian epithelial tumors.
Ovarian metastasis following gallbladder carcinoma
Abstract
BACKGROUND: Mucinous ovarian cancer raises problems of differential diagnoses because it is often difficult to distinguish the primary from the metastatic form. Most metastatic ovarian tumors originate from the gastrointestinal tract, mainly colorectal, gastric, pancreatic; the gallbladder is a very rare source of ovarian metastases.
CASE: We report a case of ovarian metastases from a gallbladder cancer, incidentally diagnosed more than 2.5 years earlier during a laparoscopic intervention for biliary lithiasis.
CONCLUSION: The interest of this case lies in the long progression-free survival, the venous thromboembolism syndrome that preceded by a few months the diagnosis of the ovarian mass and the discrepancy between the radiologic and the laparoscopic stage assessment.
The pathology of and controversial aspects of ovarian borderline tumours
Abstract
PURPOSE OF REVIEW: Ovarian borderline tumours are relatively uncommon, but not rare, neoplasms. Pathologists and oncologists often struggle with various aspects of borderline tumours which are sometimes controversial and poorly understood.
Wednesday, June 09, 2010
Genetic and Clinical Predictors for Breast Cancer Risk Assessment and Stratification Among Chinese Women
CONTEXT AND CAVEATS
Prior knowledge
Most of the genetic variants identified in genome-wide association studies of breast cancer conducted primarily among women of European ancestry have not been validated in Asian women. Consequently, no risk assessment model that incorporates both genetic and clinical predictors is currently available to predict breast cancer risk in this population.
Study design
Case–control study evaluating associations between the 12 single-nucleotide polymorphisms identified as risk variants and the risk of breast cancer among Chinese women participating in the Shanghai Breast Cancer Study as well as the cumulative risk of breast cancer associated with combinations of these risk variants. A risk assessment model that incorporates both newly identified genetic variants and traditional risk factors was developed, and its performance in risk prediction was evaluated.
Contribution
Eight of the 12 single-nucleotide polymorphisms were also associated with the risk of breast cancer among Chinese women. An aggregate measure of the combined effect of multiple genetic risk variants had moderate discriminatory accuracy by itself but in combination with established risk factors for breast cancer showed promise for stratifying women into high- vs low-risk groups.
Implications
A risk assessment model that includes both genetic markers and clinical predictors may be useful to classify Asian women into relevant risk groups for cost-efficient screening and other prevention programs.
Limitations
The moderate discriminatory accuracy provided by the full risk assessment model established in this study is inadequate for cancer diagnosis and screening. The absolute risk estimates provided by the model would be applicable only to populations with rates comparable to those of Shanghai.
Paradigm Change Suggested for Ovarian Cancer
Note: this website requires registration/free
"Women with biochemically recurrent ovarian cancer who take tamoxifen can gain an additional month of progression-free survival and have fewer side effects than women taking thalidomide, according to a study presented at the recent Society for Gynecologic Oncology’s annual meeting (abstract 2)"
“This is a very well-tolerated, very inexpensive drug, and now we have a randomized controlled, Phase III trial conducted by a cooperative group showing that it actually improves the time to subsequent disease progression,” said Maurie Markman, MD, vice president for clinical research at the University of Texas M.D. Anderson Cancer Center in Houston, who was not involved with the study...."cont'd
Late-stage ovarian cancer therapy shows promise in phase I trial: IU News Room: Indiana University Decitabine/Carboplatin
Note: reference to carbo reaction
MedEffect Canada - 2010 - Advisories, Warnings and Recalls
June
* CIPROFLOXACIN INJECTION - Voluntary Recall
o Notice to Hospitals [2010-06-09]
per Wiki: "Ciprofloxacin is marketed worldwide with over three hundred different brand names. In the United States, Canada and the UK, it is marketed as Baycip, Ciloxan, Ciflox, Cipro, Cipro XR, Cipro XL, Ciproxin and most recently, Proquin. Additionally, ciprofloxacin is available as a generic drug under a variety of different brand names and is also available for limited use in veterinary medicine."
Survival benefit from ovarian metastatectomy in colorectal cancer patients with ovarian metastasis: a retrospective analysis
Abstract
PURPOSE: A recent study demonstrated that colorectal cancer (CRC) with ovarian metastases was less responsive to chemotherapy compared with extraovarian metastases. Hence, the ovary may actually represent a "sanctuary" for metastatic cells from CRC. The aim of the study was to investigate the impact of ovarian metastatectomy on survival of CRC patients with ovarian metastasis.
Oncology Videos - ASCO 2010 Highlights (American Society of Clinical Oncology) Dr. Bradley Monk MD of the University of California Irvine talks about gynecological oncology, GOG 218, ovarian cancer, and angiogenesis
Note: Ascites/Avastin as single agent and or chemo GOG 218
Hereditary Cancer in Clinical Practice | Full text | Cancer risk in MLH1, MSH2 and MSH6 mutation carriers; different risk profiles may influence clinical management
Table 2:
Median age and range at diagnosis of Lynch syndrome
MLH1 MSH2 MSH6
Colorectal cancer 47 (25-79) 44 (20-82) 53 (32-84)
Endometrial cancer 51 (46-54) 46 (36-55) 56 (47-67)
Ovarian carcinoma 52 (52-52) 47 (45-48) 49 (35-51)
Small bowel cancer 54 (54-54) 36 (23-49) -
Transitional cell carcinoma - 58 (32-59) -
"The aim of the present study was to calculate the cumulative risk
of LS related cancers in proven MLH1, MSH2 and MSH6 mutation carriers."
"Furthermore, some studies have suggested that extracolonic cancers are more often observed in MSH2 mutation families compared to MLH1 mutation families."
press release: Clarient Receives Patents for Taxane Biomarker - TLE3 (gene)
Note: Transducin-like enhancer protein 3 is a protein that in humans is encoded by the TLE3 gene
"Clarient, Inc., a premier technology and services resource for pathologists, oncologists and the pharmaceutical industry, today announced that the United Kingdom Patent Office has granted a U.K. patent on the Company's TLE3 biomarker, a marker which may be used to predict which cancer patients will respond favorably to taxane therapy. In addition, the Company has received a Notice of Allowance from the United States Patent and Trademark Office (USPTO) for a U.S. patent on the TLE3 biomarker. Other patents for the TLE3 biomarker are pending in the U.S., Canada, Japan, China, India and elsewhere in Europe.
The U.S. patent will cover uses of the TLE3 biomarker in breast cancer. The U.K. patent covers uses of TLE3 in breast, lung and ovarian cancers.
Taxanes are important cancer therapeutics which, in combination with other cancer therapies, can markedly improve a patient's response rate to therapy. However, taxanes also carry with them a significant incidence of severe side effects, making it important to identify which patients will most likely benefit from the therapy.
"Given the frequent prescription of taxanes in the U.S., the U.K. and elsewhere in Europe and the world, we are very excited about the granting of these patents and the protection they provide our taxane sensitivity marker," said Clarient Vice Chairman and CEO Ron Andrews."
Munk Debates - The Debates
watch, listen and read:
June 7, 2010
Topic: I would rather get sick in the United States than Canada.
Pro Dr. William Frist Dr. David Gratzer
Con Dr. Howard Dean Dr. Robert Bell
Canadians warming to controversial medical user-fees, poll finds - The Globe and Mail
Note: see prior posting regarding 'Monk Debates'
WHO Responds to BMJ Report - Medical News
Note: see prior posting regarding criticisms of WHO (June 2010)
"Financial ties to the pharmaceutical industry did not play a role in the declaration and handling of the H1N1 influenza pandemic, said Margaret Chan, MD, MPH, secretary-general of the World Health Organization.
"At no time, not for one second, did commercial interests enter my decision-making," she wrote in a letter to the editors of the BMJ, which published a report last week detailing undisclosed conflicts of interest among researchers advising the WHO.
The implication of the report was that these ties to industry may have influenced some of the guidance the advisers were giving to the WHO.
"Without question, the BMJ feature and editorial will leave many readers with the impression that WHO's decision to declare a pandemic was at least partially influenced by a desire to boost the profits of the pharmaceutical industry," Chan wrote. "The bottom line, however, is that decisions to raise the level of pandemic alert were based on clearly defined virological and epidemiological criteria. It is hard to bend these criteria, no matter what the motive."
Although Chan disagreed with any implication of untoward influence from industry, she agreed that difficult questions about conflicts of interest are warranted...."
Repeat posting: Controversies in Targeted Therapy: Management of Recurrent Ovarian Cancer—Practical Case-Based Discussions CME (3)
1 Controversies in Targeted Therapy: Management of Recurrent Ovarian Cancer—Webcast (Activity OCPS01)1942 (MARCH 2010)
2 Using Targeted Therapies in a Real-World Setting—Podcast Series (Activity OCPS02)1943.01 (APRIL 2010)
3 Personalizing Treatment and Managing Patient Concerns—Podcast Series (Activity OCPS03)1943.02 (MAY 2010)
Registry Data Point to Diclofenac as Deadliest NSAID
Note: discusses adverse/risks of numerous NSAID's
Correlogic Systems Obtains CE Mark for OvaCheck® | SYS-CON MEDIA
media: June 9th: "Correlogic Systems, Inc. announced today that OvaCheck, the company's blood test for the detection of epithelial ovarian cancer, has fulfilled European Union regulatory requirements (CE marking) for distribution and sale of the test. The path is now cleared for the test to be made available to patients in Europe through their physicians...."
Molecular blockade of VEGFR2 in human epithelial ovarian carcinoma cells
Note: ACOR members see notes from Chicago
Abstract (in research/technical):
"Our findings highlight the possible confounding events that may affect the usefulness of RNAi in a therapeutic setting for disrupting EOC cell survival in ascites."
Endocrine tumors of the appendix: a pathologic review
Abstract
CONTEXT: Although rare, appendiceal endocrine tumors are the most common neoplasms of the appendix. Pathologic analysis is important for guiding the management of patients.
OBJECTIVE: To provide recent data that focus on the pathology of endocrine tumors of the appendix including classifications and guidelines for patient management.
DATA SOURCES: A review of the recent literature including TNM classifications and patient management guidelines.
CONCLUSIONS: Appendiceal endocrine tumors are separated into 2 main groups: classic endocrine tumors and goblet cell carcinoids. They can be classified according to World Health Organization and TNM classifications. Evaluation of their prognoses and risks of malignancy, according to these classifications, depends on several parameters including tumor size, proliferation rate, and infiltration of appendiceal wall and mesoappendix. Most patients with classic endocrine tumors of the appendix have a favorable prognosis. Indications for postappendectomy, complementary surgery, which are still controversial, especially for tumors between 1 and 2 cm, are presented and discussed. In contrast, in patients presenting with a goblet cell carcinoid, a right hemicolectomy after the initial appendectomy is considered the standard surgical intervention.
Appendiceal mucinous neoplasms: controversial issues - pathology
Abstract:
"...reviewed is the largely resolved controversy about whether ovarian mucinous tumors in this setting are separate primaries or are metastases from the appendiceal tumor."
June 8, 2010 SGO Statement on GOG 218 Phase III Trial Study Results (Avastin)
|  | ||||
Scaling Laws for Plasma Concentrations and Tolerable Doses of Anticancer Drugs -- Cancer Research
Abstract:
General scaling laws are developed for projecting measurements of the plasma concentrations of anticancer drugs from laboratory animals to humans and among humans of different sizes. Associated scaling laws for critical drug doses are established from these laws. Broad categories of single and periodic i.v. bolus dosings are considered. Validity of the relations is shown using measurement from the literature for several well-known cytotoxic agents. The scaling theory is also shown to apply to novel anticancer drugs now available or presently under development, as represented by the p.o. administered prodrug capecitabine, the gene silencing inhibitor zebularine, and the blood vessel inhibitor bevacizumab(Avastin). Scaling considerations for the modern practice of combination chemotherapy are also discussed.
JAMA -- Abstract: Genome-wide Analysis of Genetic Loci Associated With Alzheimer Disease, May 12, 2010
"Conclusions Two genetic loci for AD were found for the first time to reach genome-wide statistical significance. These findings were replicated in an independent population. Two recently reported associations were also confirmed. These loci did not improve AD risk prediction. While not clinically useful, they may implicate biological pathways useful for future research."
Future Oncology - Summary - Different volatile signals emitted by human ovarian carcinoma and healthy tissue
Note: in plain english this refers to a small study using 'electronic' smelling (eg. past articles regarding dogs with the ability to 'smell' ovarian cancer)
Future Oncology -- Full Text - Cancer immunotherapy: focusing on the young, neglecting the old
"...Undoubtedly we should pay more attention to the effect that aging has on the immune system. To optimally stimulate an anti-tumor immune response in the old, it is necessary to identify and understand the intrinsic defects of the old immune system and use relevant models that closely reflect those of cancer patients, where self-tolerance and aging are present simultaneously. Then it will be possible to develop cancer immunotherapeutic strategies that are customized to be effective in the young and the old."
Tuesday, June 08, 2010
One to 2-Year Surveillance Intervals Reduce Risk of Colorectal Cancer in Families With Lynch Syndrome
Background & Aims
Two percent to 4% of all cases of colorectal cancer (CRC) are associated with Lynch syndrome. Dominant clustering of CRC (non-Lynch syndrome) accounts for 1%–3% of the cases. Because carcinogenesis is accelerated in Lynch syndrome, an intensive colonoscopic surveillance program has been recommended since 1995. The aim of the study was to evaluate the effectiveness of this program.
Conclusions
With surveillance intervals of 1–2 years, members of families with Lynch syndrome have a lower risk of developing CRC than with surveillance intervals of 2–3 years. Because of the low risk of CRC in non-Lynch syndrome families, a less intensive surveillance protocol can be recommended.
Anti-MUC1 Antibodies and Ovarian Cancer Risk: Prospective Data from the Nurses' Health Studies — Cancer Epidemiology, Biomarkers & Prevention
Conclusion: Anti-MUC1 antibodies evaluated several years before diagnosis may be associated with lower risk of subsequent ovarian cancer in women <64 years old at assessment.
Impact: Key elements of an “immune model” to explain ovarian cancer risk factors are confirmed and should be evaluated in larger prospective studies.
Subscribe to:
Posts
(
Atom
)
