Tuesday, February 02, 2016
Monday, February 01, 2016
Expression of p53 and HER2/Neu in Kenyan Women With Primary Ovarian Carcinoma
abstract
Ovarian carcinomas are a leading cause of cancer mortality among women. Two of the more commonly described markers of prognostic significance in primary ovarian carcinomas are p53 and HER2/neu. Overexpression of both markers is associated with poor prognosis. This study aimed to determine the frequency and pattern of p53 and HER2/neu expression in primary ovarian carcinomas in Kenyan women and to describe the clinical and pathologic features of ovarian carcinomas diagnosed at 3 different hospitals in Kenya. Primary ovarian carcinomas diagnosed at the Departments of Pathology at Aga Khan University Hospital, Nairobi; the Aga Khan Hospital, Kisumu; and the AIC Kijabe Hospital in Kenya over a period of 3 years from January 2009 to December 2011 were recorded. Sixty-seven ovarian carcinomas were identified and blocks retrieved from archives. Hematoxylin-eosin-stained slides of these were reviewed and appropriate sections were stained for p53 and HER2/neu using standard immunohistochemical techniques. The primary outcome was presence and intensity of staining for p53 and HER2/neu. The most frequent malignancy was serous carcinoma. A total of 43.3% (95% confidence interval, 32.1%-55.2%) of carcinomas were positive for p53, and 13.4% (95% confidence interval, 7.2%-23.6%) were positive for HER2/neu. Serous carcinoma and adenocarcinoma, not otherwise specified were more likely to be positive for p53. There was no association noted between the histologic grade or pathologic stage and positivity for either p53 or HER2/neu. The expression of p53 and HER2/neu in primary ovarian carcinomas in Kenyan women is not different from that described in the literature.
(radiation) Prospective Assessment of the Oncogenic Risk to Patients from Fluoroscopy during Trauma Surgery
abstract
OBJECTIVE:
Concern about radiation exposure during surgery has focused on surgeon exposure. However, the patient receives exposure that is more direct and, in surgery about the pelvis and hip, internal pelvic non-skeletal organs often cannot be shielded without obscuring the region of surgical interest. The purpose of this study was to prospectively evaluate patients' radiation exposure during fracture surgery of the acetabulum, pelvic ring, and femur to calculate future cancer incidence (CI).DESIGN:
Prospective Descriptive Cohort SETTING:: Level One Trauma Center PATIENTS/PARTICIPANTS:: 108 patients with acetabulum, pelvic, or femur fractures requiring operative repair were prospectively enrolled.INTERVENTION:
Dosimeters were placed in locations determined for each surgery type by a medical physicist.MAIN OUTCOME MEASUREMENTS:
Demographics, operative records, and average x-ray emission energy were recorded. Effective dose (ED), specific organ doses, and lifetime cancer incidence (CI) for a 30-year-old patient were calculated.RESULTS:
Diagnoses included 27 acetabular fractures, 30 intertrochanteric femur fractures, 26 femoral shafts, and 25 pelvic ring injuries. Patients with pelvic ring injuries received the highest ED at 0.91 ± 0.74 mSv. The average lifetime increase in CI, for any cancer type, after pelvic ring fixation is 0.0097% for females and 0.0062% for males. The greatest mean single-organ dose to the ovaries (3.82 ± 3.34 mGy) occurred during pelvic ring surgery, correlating to an increased ovarian cancer risk of 0.0013%. The greatest mean single-organ dose to the prostate (6.81 ± 5.91 mSv) also occurred during pelvic surgery, correlating to increased prostate cancer risk of 0.0024%CONCLUSIONS:: Fracture surgery to the pelvis and femur are exceptionally fluoroscopy-dependent; however, the radiation exposure incurred represents a relatively small increased risk of future cancer development in patients.
Comparing the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA)
abstract
Comparing the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA): Two equivalent ways to differentiate malignant from benign ovarian tumors before surgery?
AIM:
To evaluate the prediction of malignancy in women with pelvic masses using the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA).PATIENTS AND METHODS:
Three hundred eighty four women operated due to an ovarian mass were enrolled between January 2010 and June 2015. All patients had histopathological diagnosis, HE4 and CA125 measurement. CPH-I and ROMA were calculated and their performances compared in two distinct scenarios: 1) for the discrimination of benign ovarian disease from epithelial ovarian cancer (EOC), non-epithelial ovarian cancer, borderline ovarian tumors (BOT) and ovarian metastases, and 2) for the discrimination of benign disease from EOC. Receiver Operator Characteristics' Areas Under the Curves (AUC) were calculated for CPH-I and ROMA and compared.RESULTS:
Of the 384 women, 224 presented a benign ovarian tumor, 32 BOT, 87 EOC, 26 non-epithelial ovarian cancer, and 15 had ovarian metastases. The best AUCs were obtained for the discrimination of EOC from benign tumors. CPH-I performed slightly better than ROMA, and both approached 89% sensitivity and 85% specificity. When all malignant tumors (EOC, BOT, ovarian metastases and non-epithelial ovarian cancer - entire cohort) were included, the performance of CPH-I and ROMA declined to nearly 72%, although the specificity remained close to 85%.CONCLUSION:
CPH-I and ROMA performed similarly well for the discrimination of EOC from benign ovarian tumors. However, caution is necessary since, in practical situations, where all the histological possibilities for malignant ovarian tumors must be considered, the sensitivity of CPH-I and ROMA may not surpass 70%.Illumina Providing Genomic Analysis for Precision Medicine
Science news
1 February 2016. Illumina Inc., a developer of genetic systems, is analyzing genomic data at four medical centers to integrate with patients’ electric health records for precision medicine. The San Diego company’s analytical services are expected to sequence and characterize the genomes of more than 200,000 individuals in the U.S. and Canada.
Medical centers taking part in the initiative are Vanderbilt University in Nashville, University of Colorado in Denver, Partners HealthCare in Boston, and Montreal Heart Institute in Quebec, Canada. Vanderbilt is providing 100,000 patients for the project, with the other medical centers offering between 25,000 and 50,000 participants.
The medical centers plan to use the data to discover underlying genetic factors contributing to heart disease, cancer, Alzheimer’s disease, bipolar disorder, and Crohn’s disease, among others. Each facility has a biobank, where specimen samples are collected and will be analyzed by Illumina. Each medical center also uses electronic records for storing patients’ clinical data as well as the genomic analyses.
Illumina will conduct its analysis with genotyping systems that the company says identify mutations and variations quickly. The company also expects to offer methylation sequencing, useful for identifying epigenetic factors, those outside the genome that influence gene expression.
Vanderbilt University, providing about half of the samples, will add the Illumina analyses to its BioVu collection of de-identified blood samples offered by patients with their consent. The university says it has some 150 research studies underway making use of BioVu. Nancy Cox, director of Vanderbilt’s Genetic Institute, says in an Illumina statement that BioVu “is at the core of a vision that will combine genome variation, biomarker data, patient electronic medical record information and pharmacogenomic data to advance personalized medicine.”
Montreal Heart Institute, offering about a quarter of the samples, will use Illumina’s multi-ethnic genotyping services to identify genetic predictors of responses to drugs for treating cardiac and metabolic disorders. A part of those samples, says the institute, will also be included in a study following a group of patients over time who took part in an earlier clinical trial.
Terminology of chronic pain: the need to "level the playing field
open access (pdf)
Pain medicine as a separate subspecialty is in its infancy, only fairly recently being recognized as such by the American Board of Medical Specialities.1 As it continues to find its way in the ever-changing world of medicine, terminology becomes an important consideration. Terms carry tremendous impact: for example, when a patient is told he or she has “cancer”, the impact emotionally will undoubtedly make further explanation difficult. To patients and their families, the word “cancer” has the effect of being hit with an emotional baseball bat. In the pain world, there was a recent, albeit failed, attempt to change the name of pain specialists to “algiatrists”.2 It was thought this would help define what such specialists did as opposed to other specialties. Accordingly, terminology matters, yet little attention has been paid to the terms we use to categorize and diagnose our patients. “Chronic cancer pain” and “chronic noncancer pain” are replete in the literature; however, the distinction here is actually obscure. A patient with pain from a cancer etiology has no different physiology than a patient with pain of noncancer etiologies.
Download Article [PDF]
Effectiveness of Prevention Strategies for Contrast-Induced Nephropathy: A Systematic Review and Meta-analysisEffectiveness of Prevention Strategies for CIN
open access: Effectiveness of Prevention Strategies for Contrast-Induced Nephropathy: A Systematic Review and Meta-analysisEffectiveness of Prevention Strategies for CIN
Limitation: Too few studies were done in patients receiving IV contrast media.
Comparative Effect of Contrast Media Type on the Incidence of Contrast-Induced Nephropathy
open access: Comparative Effect of Contrast Media Type on the Incidence of Contrast-Induced Nephropathy: A Systematic Review and Meta-analysisComparative Effect of Contrast Media Type
Limitations: Few studies compared LOCM. Procedural details about contrast administration were not uniformly reported. Few studies specified clinical indications or severity of baseline renal impairment.
Intraperitoneal Therapy For Ovarian Cancer With Carboplatin Trial - Full Text View - ClinicalTrials.gov
Full Text View - ClinicalTrials.gov
Japanese Gynecologic Oncology Group
| Intervention | Phase | |
|---|---|---|
|
Drug: Paclitaxel(intravenous) + Carboplatin(intravenous) Drug: Paclitaxel(intravenous) + Carboplatin(intraperitoneal) |
Phase 2 Phase 3 |
JCO: Discussion - Intraperitoneal Therapy for Ovarian Cancer
Reply to F.M. Muggia
- Corresponding author: Michael A. Bookman, MD, Arizona Oncology, 603 N Wilmot Rd, Suite 151, Tucson, AZ 85711
+ Author Affiliations
Muggia1 offers some interesting comments on our own editorial,2
and we appreciate the opportunity to briefly respond. Of note, we
believe that new approaches might actually take us further
than anticipated because of individualized therapeutic
decisions, early incorporation of synthetic lethality and immune
checkpoint
inhibition, exploitation of the peritoneal-tumor
microenvironment, and development of new molecular targets associated
with
drug resistance. However, these topics were clearly
beyond the scope of a short editorial regarding intraperitoneal (IP)
chemotherapy.
We also need to learn from the limitations,
as well as from the strengths, of prior clinical research. Whether IP
cytotoxic
chemotherapy should be a standard component of future
research should not simply be accepted, but should be based on ongoing
scientific and clinical validation as well as
prioritization of limited resources. In this regard, we should aspire to
move
beyond citing pharmacologic advantage, which is
conveniently measured within the peritoneal infusate, but is of
uncertain
relevance to the tumor or host. We need to broadly
consider the complex biologic and clinical implications of drug exposure
within the tumor microenvironment, a unique feature of
this disease.
It is worth remembering that none of the
reasonable modifications to the IP regimen of the GOG-0172 trial have
been validated
in a prospective randomized trial, and there are no
data to support that IP administration of cisplatin 75 mg/m2,
or that substituting IP carboplatin (area under the curve = 6) or
changing the paclitaxel dose and schedule, will be superior
to treatment with a standard intravenous
platinum-taxane therapy. This could be especially relevant if the
pharmacologic advantage
is a truly critical determinant of long-term outcomes.
In addition, primary intravenous therapy has evolved from the GOG-0172
trial to include the substitution of carboplatin and
the potential incorporation of dose-dense, weekly paclitaxel or
bevacizumab.
It is clear that we need to make appropriate
adjustments in IP treatment delivery, but this would be much easier to
accomplish
if we understood the targets and mechanisms of IP
chemotherapy that are associated with clinical benefit.
Mismatch Repair Protein Expression in Clear Cell Carcinoma of the Ovary
Mismatch Repair Protein Expression in Clear Cell Carcinoma of the Ovary: Incidence and Morphologic Associations in 109 Cases
Abstract
Several
morphologic features have been reported to be predictive of abnormal
expression of mismatch repair (MMR) proteins in endometrial and colon
carcinomas. Although it is known that abnormal MMR expression is
increased in frequency in ovarian endometrioid and clear cell
carcinomas, no such histologic correlation has been identified. We
reviewed 109 unselected ovarian clear cell carcinomas for specific tumor
characteristics (architecture, nuclear atypia, signet ring cells,
stromal hyalinization, background precursor) and inflammatory response
(peritumoral lymphocytes found along the leading edge of the tumor,
intratumoral stromal inflammation found within the tumor, percentage of
plasma cells in the intratumoral stromal inflammation,
tumor-infiltrating lymphocytes) and performed immunohistochemistry for
all 4 MMR proteins. Abnormal MMR expression was identified in 6% of
tumors and included MSH2/MSH6
(3), MLH1/PMS2 (1), MSH6 (1), and PMS2 (1). These patients had a mean
age of 40 (range, 31 to 48) years, which contrasted with a mean of 53.2
(range, 28 to 82) years for the overall cohort. One had a concurrent
diagnosis of endometrial carcinoma, whereas another had a family history
of endometrial carcinoma. None had a personal/family history of colonic
carcinoma. Tumors with diffuse intratumoral stromal inflammation and
peritumoral lymphocytes were more frequently associated with MMR loss on
univariate analysis (P<0.001 and 0.047, respectively) with diffuse
intratumoral stromal inflammation remaining a significant independent
predictor on multivariate analysis. None of the other morphologic
features evaluated reached statistical significance. Although previous
series have been unable to identify a relationship between histology and
MMR expression, this study identified a correlation with diffuse
intratumoral stromal inflammation and peritumoral lymphocytes, 2
features that potentially could be selected for MMR analysis if
corroborated by other studies.
Long-term Benefit of Tumor Volume-Directed Involved Field Radiation Therapy in the Management of Recurrent Ovarian Cancer
abstract
define: IFRT + delivering radiation to only those areas of the body involved
OBJECTIVES:
This study aimed to report on long-term effectiveness of involved field radiation therapy (IFRT) in the salvage of localized recurrent ovarian cancer (ROC).METHODS:
A retrospective analysis of 27 patients with a diagnosis of epithelial ovarian cancer who received tumor volume-directed IFRT for localized extraperitoneal recurrences (either as consolidation after cytoreductive surgery (CRS) or as attempted salvage if unresectable) forms the basis of this report. All patients were heavily pretreated with multiple chemotherapy regimens. Involved field radiation therapy was primarily with external beam (median dose, 50.4 Gy). Local recurrence-free survival (LRFS) was defined as freedom from in-field recurrences and was considered as a measure of effectiveness of radiotherapy. Statistical analyses evaluated association between disease-free survival, overall survival, LRFS, and various prognostic factors. Comparison was also made with a similar but unmatched cohort with localized recurrences salvaged by additional chemotherapy instead of local therapies (NIFRT group).Preoperative experience for public hospital patients with gynecologic cancer
abstract
Preoperative experience for public hospital patients with gynecologic cancer: Do structural barriers widen the gap?
BACKGROUND
Widespread
disparities in care have been documented in women with gynecologic
cancer in the United States. This study was designed to determine
whether structural barriers to optimal care were present during the
preoperative period for patients with gynecologic cancer.
METHODS
A
retrospective review was conducted for patients undergoing surgery for a
gynecologic malignancy at a public hospital or a private hospital
staffed by the same team of gynecologic oncologists between July 1, 2013
and July 1, 2014.
RESULTS
Two
hundred fifty-seven cases were included for analysis (public hospital,
69; private hospital, 188). Patients treated at the private hospital
were older (58 vs 52 years; P = .004) and had similar medical
comorbidities (median Charlson comorbidity index at both hospitals, 6)
but required fewer hospital visits in preparation for surgery (2 vs 4; P < .001). Public hospital patients had a longer wait time from the diagnosis of disease to surgery (63 vs 34 days; P
< .001). According to a multiple linear regression model, the public
hospital setting was associated with a longer interval from diagnosis
to surgery with adjustments for the insurance status, age at diagnosis,
cancer stage, and number of preoperative hospital visits (P < .001).
CONCLUSIONS
Patients at the public hospital were subject to a greater number of preoperative visits and had to wait longer for surgery than patients at the private hospital. Attempts to reduce health care disparities should focus on improving efficiency in health care delivery systems once contact has been established.Meet the experts at our new event: 'Science, theory and advances in ovarian cancer' conference June 2016 (UK)
Target Ovarian Cancer
Target Ovarian Cancer is very proud to present its second flagship 'Ask the Experts' event: 'Science, theory and advances in ovarian cancer'. In June 2016, in Birmingham, we will bring together eminent experts for presentations and Q&As on the cutting edge of ovarian cancer news and research. This free information event is open to all women with ovarian cancer, their families and their friends.
Leading figures including oncologists, clinical nurse specialists, GPs, researchers and more will give presentations on a range of topics including:
- screening, risk and earlier diagnosis
- treatment and research
- living well with ovarian cancer
PR release needs more evidence for its exceptional ovarian cancer claims
HealthNewsReview.org
Our Review Summary
This news release summarizes a review article published in Nature Reviews Clinical Oncology which assesses the available evidence and makes recommendations concerning the treatment of advanced ovarian cancer. The author of the review argues that adopting a more aggressive standard of treatment for this cancer type that involves locally directed adjuvant chemotherapy could increase cure rates from 20% to 50%. The news release uses some of the language in the review but, unsurprisingly, it appears more optimistic than the perspective piece. The release doesn’t address costs or harms related to such a course of treatment, nor does it give readers any information about how the original article reached the conclusion that survival rates could be increased up to 50 percent. Exceptional claims require exceptional evidence, and that’s missing here.....
Saturday, January 30, 2016
Understanding genistein in cancer: The “good” and the “bad” effects: A review
abstract
Highlights
- •
- Genistein biological activities strongly differ in relation to doses applied.
- •
- Genistein targets primarily estrogen receptors and tyrosine kinases.
- •
- Potential therapeutic effects of genistein may depend upon the pleiotropic nature of the molecule.
Abstract
Nowadays,
diet and specific dietary supplements are seen as potential adjuvants
to prevent different chronic diseases, including cancer, or to
ameliorate pharmacological therapies. Soybean is one of the most
important food components in Asian diet. A plethora of evidence supports
the in vitro and in vivo anticancer effects of
genistein, a soybean isoflavone. Major tumors affected by genistein here
reviewed are breast, prostate, colon, liver, ovarian, bladder, gastric,
brain cancers, neuroblastoma and chronic lymphocytic leukemia. However,
it is not always clear if and when genistein is beneficial against
tumors (the “good” effects), or the opposite, when the same molecule
exerts adverse effects (the “bad” effects), favouring cancer cell
proliferation. This review will critically evaluate this concept in the
light of the different molecular mechanisms of genistein which occur
when the molecule is administered at low doses (chemopreventive
effects), or at high doses (pharmacological effects).
Keywords
- Soybean;
- Genistein;
- ERα/ERβ;
- Tyrosine kinases;
- miRNA
Genetic discrimination law urgently needed, medical experts say (Canada)
CBC News
(Toronto) Sick Kids Hospital genetics head calls absence of confidentiality legislation 'paralyzing'
"There's no protection against genetic discrimination at all," Dr. Ronald Cohn, chief of genetics at the Hospital for Sick Children in Toronto, told CBC News.
Bill S-201 — also known as the Genetic Non-Discrimination Act — passed second reading in the Senate earlier this week. The legislation would specifically prohibit insurance companies, employers and other third parties from accessing people's genetic test results.....
External Links
Cancer Conversations Podcast – Episode #2: The Truth About BRCA Testing and Genetic Risk
Podcast – Episode #2 (24 min)
Although only a small percentage of breast cancers are considered hereditary, genetic testing and cancer risk — specifically the BRCA1/2 genes — have made many headlines in recent years. But what exactly does it mean to have a BRCA mutation, and what do women need to know?
In this Cancer Conversations podcast episode, Huma Rana, MD, clinical director of Dana-Farber’s Center for Cancer Genetics and Prevention, gives an overview of the link between genetics and women’s cancers, and why certain women have a higher risk for developing disease.
Listen to the podcast episode below or click “download” to listen later. Subscribe options are also available via iTunes, Google Play and RSS.
The Cancer Conversations series features Q&A-style conversations with Dana-Farber physicians, clinicians, and researchers. Topics include breast cancer research, precision cancer medicine, integrative therapies, cancer genetics, and more. Visit the Cancer Conversations page for more episodes.
Learn more about Dana-Farber’s Cancer Podcast Series.
Podcast: Play in new window | Download
Prognostic factors in Polish patients with BRCA1-dependent ovarian cancer
open access
Background
Treatment outcomes appear to be better for ovarian cancer (OC) patients carrying the
BRCA1/2 germline mutation than for patients with sporadic OC. However, most published data
are for North American, British and Jewish populations. There have been very few studies
on treatment outcomes in Central and Eastern European patients with OC. The aim of
this study was to analyse prognostic factors in Polish patients with BRCA1-dependent OC (BRCA1-OC).
Conclusion
Prognostic factors for favourable treatment outcomes in Polish patients with BRCA1-OC do not appear to differ from those in patients with sporadic OC. The incidence
of the endometrial subtype of OC was relatively high (34.9 %) among women in the study.
This was unexpected and has not been reported previously. This subtype of OC was an
independent prognostic factor for favourable treatment outcomes.
Trends in gynecologic cancer among elderly women in Denmark, 1980–2012
abstract
For ovarian and Fallopian tube cancers the incidence was almost constant, whereas the average annual number of deaths decreased over time from 466 in 1980 to 396 in 2012. The mortality rates were clearly separated by age groups with mortality rates 3–4 times higher among the elderly. The mortality rate decreased among women less than 70 years during the entire period.
Friday, January 29, 2016
Are Early Relapses in Advanced-Stage Ovarian Cancer Doomed to a Poor Prognosis?
PLOS ONE (open access)
Objective
Early recurrence (ER) after completion of therapeutic regimen in advanced-stage ovarian cancer is a challenging clinical situation. Patients are perceived as invariably having a poor prognosis. We investigated the possibility of defining different prognostic subgroups and the parameters implicated in prognosis of ER patients.Conclusion
ER (early recurrence) in advanced-stage ovarian cancer does not inevitably portend a short-term poor prognosis. RD (residual disease) status after initial cytoreduction strongly modulates OS, that gives additional support to the concept of maximum surgical effort even in patients who will experience early recurrence. The heterogeneity in outcomes within the ER group suggests a role for tumor biology in addition to classical clinical parameters.SGO Annual Meeting (March 2016) on Women's Cancer San Diego (abstracts)
SGO
Abstract titles now available
Session times, abstract titles, authors and institutions
are now available online for the SGO Annual Meeting in San Diego. Full
abstracts will become available on the day of the session on which they
will be presented.
Routine Clinical Practice for Patients With Recurrent Ovarian Carcinoma: Results From the TROCADERO Study
open access
This study characterized the clinical features and prognosis of patients with recurrent ovarian carcinoma with respect to platinum sensitivity. The primary objective was to evaluate PFI among PPS patients who received platinum-containing treatment at first recurrence relative to those patients who did not. Data regarding clinical characteristics, incidence and duration of clinical events, and treatment regimen are reported.
Clinical and Pathological Characteristics of Incidental Diagnostic Early Occult Malignancy After Risk-Reducing Salpingo-Oophorectomy in BRCA Mutation Carriers
open access
CONCLUSIONS
Our study demonstrated an incidence of early occult
malignancy of 5.4% among BRCA mutation carriers who underwent RRBSO.
This falls within the middle ranges of reported data (1.3%–10.4%).
Origin sites for the discovered malignancies were in the ovaries and in
the fallopian tubes. These data support the notion that such
malignancies may originate from the fallopian tube, although the
fallopian tubes are not a unique site of origin. Further study may
explain the different origins of carcinogenesis. Continued screening of
women at high risk and recommendation of early and meticulous RRBSO are
crucial to limit the risk of ovarian and tubal carcinogenesis.
Abstract
Objective: Carriers of familial BRCA mutations are at
high risk of early development of ovarian tubal or peritoneal cancers.
The definite preventative treatment for these cases is early,
risk-reducing, bilateral salpingo-oophorectomy (BSO). The aims of the
study were to describe the incidence and source of early occult
malignancy after risk-reducing salpingo-oophorectomy in carriers of
Ashkenazi Jewish BRCA mutations and to characterize the clinical and
pathological features of this unique population.
Methods:
Data were collected retrospectively regarding women who underwent BSO
in our gynecologic oncology unit from January 2002 through July 2012,
after a positive test for a BRCA1 or BRCA2 mutation.
Results:
The following 92 cases of BRCA mutations were included: 53 BRCA1, 37
BRCA2, and 2 with both mutations. After risk-reducing
salpingo-oophorectomy, 5 (5.4%) of the patients were found to have early
occult adnexal malignancy upon pathology study. All 5 had the BRCA1 185
del-AG mutation. Three of the 5 malignancies originated from the
ovaries and 2 in the fallopian tubes with no involvement of the ovaries.
Conclusions:
A 5.4% incidence of early occult malignancy in adnexal pathology of BSO
was found in carriers of Ashkenazi Jewish BRCA mutations. Two cases
with malignant origins within the fallopian tube, while sparing the
ovaries in their entirety, support the fallopian tubes as the
originating organ for some ovarian or peritoneal malignancies in BRCA
mutation carriers.
Letter to the Editor on “Should All Cases of High-Grade Serous Ovarian, Tubal, and Primary Peritoneal Carcinomas Be Reclassified as Tubo-Ovarian Serous Carcinoma?”
open access
.....
In our opinion, the fact that one tumor type (HGSC) accounts
for more than two thirds of the cases does not justify classifying
ovarian carcinomas into only 2 types, lumping together the other four
(low-grade endometrioid, clear cell, mucinous, and low-grade serous
carcinomas) as “type 1 carcinomas”. In fact, the latter tumors are
clinically, morphologically, and molecularly distinct diseases that
individually bear resemblance neither to HGSCs nor to each other. Thus,
classifying ovarian carcinomas into just 2 types (“types 1 and 2”) is
artificial and limits progress in understanding the biology or improving
the management of the less common types of ovarian carcinomas. When
preparing this, we were reminded of the words of the eminent
Scandinavian investigators of earlier times Drs. Lars Santesson and Hans
Ludwig Kottmeier who began an essay on the classification of ovarian
tumors as follows: “Ovarian cancer is not an entity but a group of
diseases. Studies of the results of treatment must be based on
homogeneous groups of tumours and not on mixtures of histologically and
biologically different tumour types”.3
Just a few of the many differences between the entities
in the grouping “type 1” carcinoma are the following: endometrioid and
clear cell tumors have a very significant association with
endometriosis, not seen, except rarely, with mucinous carcinomas and
LGSCs. Additionally, endometrioid and clear cell carcinomas often have
an origin in adenofibromas, also rarely seen with the other 2 tumor
types. Mucinous tumors in an uncertain but definitely notable percentage
of cases are likely of teratomatous origin, which is completely lacking
for the other 3 tumor types....We think that terms such as tubo-ovarian, müllerian, or pelvic serous carcinoma should not be recommended because they create confusion for patients, physicians, and medical investigators. In view of the rarity of HGSCs associated with tubal tumor masses, it is unlikely that all HGSCs originate in the fallopian tube. In contrast, ovarian involvement is the rule in almost all cases. The term HGSC of ovary should be kept until the different origins of ovarian tumors are better understood.15REFERENCES
1. Moss EL, Evans T,
Pearmain P, et al. Should all cases of high-grade serous ovarian, tubal,
and primary peritoneal carcinomas be reclassified as tubo-ovarian
serous carcinoma? Int J Gynecol Cancer. 2015; 25: 1201–1207.
Thursday, January 28, 2016
Necessary Versus Sufficient: An Increasingly Relevant Distinction in Oncology (ref to ovarian cancer)
clinical oncology article (Markman)
In summary, it is essential that any organization, as well as individual clinicians attempting to interpret the results of clinical studies, appreciate the critical distinction between what is appropriately considered to be necessary evidence versus the ultimate mandate for sufficient evidence in the future development of specific medical recommendations, evidence-based guidelines, or public health policy.
References
- Le Tourneau C, Delord JP, Goncalves A, et al. Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicenter, open-label, proof-of-concept, randomized, controlled phase 2 trial. Lancet Oncol. 2015;16(13):1324-1334, PMID: 26342236.
- Jacobs IJ, Menon U, Ryan A, et al. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): A randomized controlled trial. Lancet. [Epub ahead of print]. DOI: http://dx.doi.org/10.1016/S0140-6736(15)01224-6.
- Buys SS, Partridge E, Black A, et al. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA. 2011;305(22): 2295-2303, PMID: 21642681.
- Grady D. Early detection of ovarian cancer may become possible. The New York Times. December 18, 2015. http://goo.gl/WN7CPT. Accessed December 22, 2015.
video: The changing Nature of Phase 1 Clinical Trials (Dr. Lillian Siu)
Chromeless Video Player (39 min)
The Changing Nature of Phase I Trials
Lillian Siu, MD, FRCRC
Lillian
L. Siu, MD, Princess Margaret Cancer Center, University of Toronto,
discussed the changing nature of phase I clinical trials, and how these
changes are influencing the development and approval trajectories of
novel cancer therapeutics.
Identification of a Japanese Lynch syndrome patient with large deletion in the 3′ region of the EPCAM gene
abstract
Germline deletion of the 3′ portion of the Epithelial Cell Adhesion Molecule (EPCAM) gene located 5′ upstream of MutS Homolog 2 (MSH2) is a novel mechanism for its inactivation in Lynch syndrome. However, its contribution in Japanese Lynch syndrome patients is poorly understood. Moreover, somatic events inactivating the remaining allele of MSH2 in cancer tissue have not been elucidated in Lynch syndrome patients with such EPCAM deletions. We identified a Japanese Lynch syndrome patient with colon cancer who evidenced germline deletion of a 4130 bp fragment of EPCAM encompassing exons 8 and 9 (c.859-672_*2170del). In normal colonic mucosa, two known fusion-transcripts of EPCAM/MSH2 generated from the rearranged gene were observed and heterozygous methylation of the MSH2 gene promoter was detected. In cancer tissue, dense methylation of MSH2 was observed and MLPA analysis demonstrated somatic deletion of the remaining EPCAM allele including exon 9, indicating that somatic deletion of EPCAM is responsible for complete inactivation of MSH2.
Preventing Damage Limitation: Targeting DNA-PKcs and DNA Double-Strand Break Repair Pathways for Ovarian Cancer Therapy
open access
...The promise of PARP inhibition strategies and DNA-PKcs as a therapeutic target highlights the importance of understanding the clinical significance of the functioning and defective DNA repair mechanisms in cancer. There remains the need to identify reliable biomarkers of tumor cell response and resistance to therapies targeting DNA repair proteins and indeed to identify and validate new therapeutic targets from this critical but insufficiently mined resource. The identification of patient subgroups who will benefit most from such strategies is also required – DDR proteins such as DNA-PKcs have been suggested to have a tumor-suppressive role in the early stages of carcinogenesis where ineffective DDR may contribute to the generation of genomic instability that drives tumor progression (99). As such, the development of DNA-PKcs inhibitions, and indeed other DDR targeted therapies, should be mindful of DNA damage thresholds that can be either oncogenic or tumor-suppressive, depending on the tumor stage. Together, such knowledge and understanding will translate into the development of new directed strategies that will help overcome clinical platinum resistance in ovarian cancer, and by that reduce patient mortality.
Ovarian Cancer Molecular Stratification and Tumor Heterogeneity: A Necessity and a Challenge
open access
The Future
Clearly, future optimal therapy for high-grade serous
ovarian cancer will depend on optimal molecular stratification and this
is just as true for bevacizumab and olaparib as it will be for future
agents. While this will help rise to the challenge of optimizing therapy
for inter-patient molecular heterogeneity, monotherapy may never
overcome intra-patient heterogeneity. If we want to improve the
durability of responses, that pool of resistant clones may need to be
narrowed by using combination therapies. Indeed, recent clinical data
for the addition of the VEGFR inhibitor, cedirinib, to olaparib have
shown a significant increase in response rate and a near-doubling of
progression free survival (47).
The majority of this benefit was in the BRCA1/BRCA2 wild-type (or
unknown) group, perhaps demonstrating that combinations can overcome
monotherapy dependencies but also highlighting that there is still a lot
to learn about biomarkers for anti-angiogenic and PARP inhibitor agents
in ovarian cancer.
Disseminated Medulloblastoma in a Child with Germline BRCA2 6174delT Mutation and without Fanconi Anemia
open access
Here, we report for the first time on a child carrying a familial heterozygous BRCA2 6174delT germline mutation, who presented with metastatic medulloblastoma. We also provide characterization of his tumor and the unique pair of medulloblastoma cell lines generated from it at diagnosis and at the time of systemic metastatic recurrence.
Wednesday, January 27, 2016
Family History of Cancer in Relation to Breast Cancer Subtypes in African American Women
abstract
Background: The evidence on the relation of family history of cancers other than breast cancer to breast cancer risk is conflicting,
and most studies have not assessed specific breast cancer subtypes.
Methods: We assessed the relation of first-degree family history of breast, prostate, lung, colorectal, ovarian, and cervical cancer
and lymphoma or leukemia, to the risk of estrogen receptor–positive (ER+), ER−,
and triple-negative breast cancer in data from the African American
Breast Cancer Epidemiology and Risk Consortium...
Results: There were 3,023 ER+ and 1,497 ER− breast cancer cases (including 696 triple-negative cases) and 17,420 controls. First-degree family history of breast cancer
was associated with increased risk of each subtype: OR = 1.76 (95% CI, 1.57–1.97) for ER+, 1.67 (1.42–1.95) for ER−, and 1.72 (1.38–2.13) for triple-negative breast cancer. Family history of cervical cancer was associated with increased
risk of ER− (OR = 2.39; 95% CI, 1.36–4.20), but not ER+ cancer. Family history of both breast and prostate cancer was associated with increased risk of ER+ (3.40; 2.42–4.79) and ER− (2.09; 1.21–3.63) cancer, but family history of both breast and lung cancer was associated only with ER− cancer (2.11; 1.29–3.46).
Conclusions: A family history of cancers other than breast may influence the risk of breast cancer, and associations may differ by subtype.
Early-Stage Clinical Trials Underestimate Small Molecule, Targeted Anticancer Drug Toxicity
OncoTherapy Network
Dose-determining phase I clinical trials may not correctly determine the appropriate doses of small molecule oncology drugs to administer in larger, later stage trials according to a new study published in Clinical Cancer Research.
The current study, conducted by researchers at The Institute of Cancer Research and the Royal Marsden Hospital NHS Foundation Trust in the United Kingdom, suggests that phase 1 dose-ranging studies do not correctly reveal the severity of side effects of these cancer agents. The result is high incidence of varying drug toxicity experienced by patients taking part in phase III oncology clinical trials testing targeted small molecule agents.......
Ultrasounds Improve Diagnosis for Ovarian CancerTrending
Blogger's Note: same subject/different source
article
.... "A simple classification based on these risk estimates may form the basis of a clinical management approach. This will hopefully facilitate choosing optimal treatment for all patients presenting with adnexal masses."
In an editorial review of the study, Dr. Beryl Benacerraf, President of the American Institute of Ultrasound in Medicine (AIUM) and Clinical Professor of Radiology and OB GYN at Brigham and Women's Hospital, commented on the innovative simplicity of this new diagnostic method.
"The investigators have finally been able to level and elevate the playing field so that everybody can practice with expert results in this regard," Benacerraf said. "Not only have the five simple rules demonstrated that you don't have to be an expert to evaluate ovarian masses accurately, but that one can do so simply, reproducibly and reliably."....
Role of Increased n-acetylaspartate Levels in Cancer
abstract
Background: The clinical and biological effects of metabolic alterations in cancer are not fully understood.
Methods: In high-grade
serous ovarian cancer (HGSOC) samples (n = 101), over 170 metabolites
were profiled and compared with normal
ovarian tissues (n = 15). To determine NAT8L
gene expression across different cancer types, we analyzed the RNA
expression
of cancer types using RNASeqV2 data available
from the open access The Cancer Genome Atlas (TCGA) website (http://www.cbioportal.org/public-portal/).
Using NAT8L siRNA, molecular techniques and histological analysis, we
determined cancer cell viability, proliferation,
apoptosis, and tumor growth in in vitro and in
vivo (n = 6–10 mice/group) settings. Data were analyzed with the
Student’s
t test and Kaplan-Meier analysis. Statistical tests were two-sided.
Results: Patients with
high levels of tumoral NAA and its biosynthetic enzyme, aspartate
N-acetyltransferase (NAT8L), had worse overall
survival than patients with low levels of NAA
and NAT8L......
Conclusion: These findings indicate that the NAA pathway has a prominent role in promoting tumor growth and represents a valuable target
for anticancer therapy.
Altered energy metabolism is a hallmark of cancer (1). Proliferating cancer cells have much greater metabolic requirements than nonproliferating differentiated cells (2,3).
Moreover, altered cancer metabolism elevates unique metabolic
intermediates, which can promote cancer survival and progression
(4,5). Furthermore, emerging evidence suggests that proliferating cancer cells exploit alternative metabolic pathways to meet
their high demand for energy and to accumulate biomass (6–8).
2016 Progress and Controversies in Gynecologic Oncology Conference - download slides
Activity Overview
prIME Oncology invites you to view downloadable slides from the 2016 Progress and Controversies in Gynecologic Oncology Conference held in Barcelona, Spain.
Bleomycin-Induced Flagellate Erythema in a Patient Diagnosed with Ovarian Yolk Sac Tumor
open access
Flagellate linear hyperpigmentation can rarely be caused by the chemotherapy agent, bleomycin. Herein, we describe the case of a 20-year-old woman treated with bleomycin for an ovarian yolk sac tumor and review the prominent features of this form of dermatitis.
2. Material
We report the case of a 20-year-old woman with no significant past medical or surgical history. An ultrasound examination demonstrated a suspicious ovarian cyst in pregnancy and the patient underwent fertility-preserving ovarian cancer resection with left oophorectomy. Routine pathological examination revealed replacement of the cyst by yolk sac tumor with a minor component of mature cystic teratoma.....
Borderline ovarian tumours: a continuing conundrum?
Commentary
Whereas benign and malignant primary tumours of the ovary are well understood clinically, the concept of borderline ones are less so. Of the epithelial tumours of the ovary, the concept is best described in serous tumours, and less so in the other types, largely because serous tumours can present with extra-ovarian nonmalignant spread at the time of diagnosis. The pathological diagnosis of a borderline tumour is essentially one of dysplasia, with no (or minimal) invasion, on good histological sampling of the ovary. In the area of ovarian serous tumours, this has been further complicated by the identification of the micro-papillary subset, and of serous epithelium involving other tissues (implants—invasive versus noninvasive) and what the diagnostic criteria are and what they mean biologically......
Why does this matter? The clinical dilemma of what do with women with a borderline ovarian tumour diagnosis is problematic in the extreme. Do these women warrant more aggressive treatment at diagnosis or can a watchful waiting policy be more appropriate? We still cannot predict which cases will/may progress with any certainty. The majority of these women are pre-menopausal, with many years of life ahead of them, and hence over-treatment may be just as harmful as under-treatment. The need for accurate pathology, and the distinction from a true low grade serous carcinoma, is vital but often very difficult. The need to exclude metastatic mucinous tumours from a primary ovarian one, even of borderline type, is well described. The questions are easy to raise, but answering them is and continues to be far harder.
The clinical implications of new insights into the origins of epithelial ovarian cancer....
open access:
The clinical implications of new insights into the origins of epithelial ovarian cancer with emphasis on the British Columbia Ovarian Cancer Prevention Initiative - J Health Specialties
Data from our centre showed that almost 20% of women who developed HGS cancer in our province had undergone a hysterectomy for benign disease prior to their diagnosis.
Up to 50 percent of women with advanced-stage ovarian cancer could be cured with 1 treatment model
Blogger's Note: an easier-to-read article vs. previously posted article on the same subject/author
medical news article
Are we ready for a blood test for cancer? (in research)
medical news article
What if screening for cancer was as easy as checking your cholesterol? That's the promise of techniques currently in development that may one day make it possible to detect the earliest stages of cancer with an annual blood draw.
So-called "liquid biopsies" involve extracting free-floating cancer cells or cancer DNA from the bloodstream (or in some cases from the urine) to get information about tumors too small or hidden to detect with standard techniques. This could make it possible for clinicians to remotely monitor how cancer patients are responding to treatment, to detect early warning signs of recurrence, and even to pick up the very first signs of cancer in otherwise healthy people....
"It's important to maintain healthy skepticism," Witte said, "But right now I'd say most researchers are cautiously optimistic."
Tuesday, January 26, 2016
Serial Patterns of Ovarian Cancer Biomarkers in a Prediagnosis Longitudinal Dataset
open access (long/technical article)
The area under the ROC curve for the panel of three biomarkers (CA125, HE4, and glycodelin) was higher than for CA125 alone for all analysed time groups, indicating that these markers can improve on sensitivity of CA125 alone for ovarian cancer detection.
We show that, in addition to HE4 (which has been shown to be the second best performing marker after CA125 in the context of screening), glycodelin is a novel and useful adjunct to CA125 for early detection of ovarian cancer. Glycodelin has only been previously tested in the diagnosed case control setting [11, 21], although with promising results. This work also supports previous studies showing the potential of HE4 [10–14, 16, 19], whilst suggesting that mesothelin, MMP7, and CYFRA 21-1 are not useful markers for the early detection of ovarian cancer. The next step in this work would be to validate these findings in a larger independent set and to test the potential of these candidates in multimarker longitudinal algorithms.
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