In the Original Investigation titled “Utilization and Outcomes of BRCA Genetic Testing and Counseling in a National Commercially Insured Population: The ABOUT Study,”1 published in the December 2015 issue of JAMA Oncology,
the conflict of interest disclosure statement in the Article
Information section was incomplete. The original statement was “Dr
Sutphen has received personal fees from InformedDNA outside the present
work. No other disclosures are reported.” This should have been “Dr
Sutphen received payment for serving as President and Chief Medical
Officer of InformedDNA, which provides a network of genetics specialists
and a library of genetic tests and hereditary conditions. No other
disclosures are reported.” The article has been corrected online.
Tuesday, February 16, 2016
Ovarian Cancer—SEER Stat Fact Sheets
SEER Stat Fact Sheets
At a Glance
- Estimated New Cases in 2015 21,290
- % of All New Cancer Cases1.3%
- Estimated Deaths in 2015 14,180
- % of All
Cancer Deaths 2.4%
Percent Surviving
5 Years
45.6% 2005-2011
5 Years
45.6% 2005-2011
Genetics of Colorectal Cancer (PDQ) - NCI - feb 2016
National Cancer Institute
Changes to This Summary (02/12/2016)
The PDQ cancer information summaries are
reviewed regularly and updated as new information becomes available.
This section describes the latest changes made to this summary as of the
date above.
Added text about the approaches that are
available to evaluate a patient with newly
diagnosed colorectal cancer (CRC) who may or may not be suspected of having
a cancer genetics syndrome.
Updated National Comprehensive Cancer Network (NCCN) as reference 73.
Updated NCCN as reference 92.
Revised Table 7 to state that NCCN recommends that if an at-risk individual is found to
not carry the APC gene
mutation
responsible for
familial polyposis in
the family, screening
as an average-risk
individual is
recommended.
Revised Table 9
to state that NCCN recommends considering colectomy and ileorectal
anastomosis in individuals aged 21 years or older with a personal
history of MYH-associated polyposis and a small adenoma burden.
Added Borelli et al. as reference 260.
Added Goldberg et al. as reference 348.
Revised text
to state that NCCN supports immunohistochemistry or sometimes
microsatellite instability testing of all CRCs diagnosed in patients
younger than 70 years if tumor tissue is available and in patients 70
years or older if they meet Bethesda guidelines.
Revised Table 11 to state that NCCN recommends initiating
CRC screening in MSH6 and PMS2 carriers between ages 25 years and 30 years or 2 to 5 years before the youngest case of CRC in
the family if before age 30 years.
Revised Table 12 to state that NCCN does not recommend
surveillance of the prostate in Lynch syndrome.
Revised text to state that an updated set of operational
criteria for the diagnosis of Cowden syndrome based on a
systematic literature review has been suggested and is
currently utilized in the NCCN guidelines.
Cancer Genetics Risk Assessment and Counseling (PDQ) - changes feb 2016
National Cancer Institute
Updated: February 10, 2016 - Changes to This Summary (02/10/2016)
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Added Robson et al. as reference 10.
Added Robson et al. as reference 5.
Added Robson et al. as reference 2.
Added Robson et al. as reference 3.
Revised text to state that multi-gene testing has
both advantages and disadvantages, and much of the
information presented in the "Multi-gene (panel) testing"
subsections of this summary is not based on empirical data but rather on commentaries.
Increased Risk for Other Cancers in Addition to Breast Cancer for CHEK2*1100delC Heterozygotes...
abstract: Increased Risk for Other Cancers in Addition to Breast Cancer for CHEK2*1100delC Heterozygotes Estimated From the Copenhagen General Population Study
For CHEK2*1100delC heterozygotes compared with noncarriers, the age- and sex-adjusted hazard ratios were 5.76 (95% CI, 2.12 to 15.6) for stomach cancer, 3.61 (95% CI, 1.33 to 9.79) for kidney cancer, 3.45 (95% CI, 1.09 to 10.9) for sarcoma, and 1.60 (95% CI, 1.00 to 2.56) for prostate cancer.
Conclusion CHEK2*1100delC heterozygosity is associated with 15% to 82% increased risk for at least some cancers in addition to breast cancer. This information may be useful in clinical counseling of patients with this loss-of-function mutation.
“It Is What It Is” (age 13) JCO Art of Oncology series
“It Is What It Is”
Presymptomatic DNA testing has introduced a new category of patients—those who do not have cancer but are at increased risk. They have been through the process of making a decision about DNA testing. When at risk, they may opt for surveillance, preventive surgery, or other ways to reduce their risk. Their frame of reference may be well known, as in BRCA; it may be less familiar, as in Lynch syndrome; or it may be obscure, as in HLRCC.
A looming challenge for the field is to provide adequate guidance based on evidence, resources, and, most importantly, the preferences of the patient.
Exciting results in immunotherapy: What do we know? | ACS (media reporting) Pressroom Blog
ACS Pressroom Blog
A story on BBC News this morning quotes researchers who say a therapy using the body’s own immune system led to more than 90% of terminally ill patients they treated going into remission. The report is based on comments made Sunday at a symposium at the American Association for the Advancement of Science (AAAS) meeting in Washington D.C. The story was then picked up by CNBC, which called the results “spectacular.”....
NIH Rare Disease Day event, on Leap Day (Feb. 29)
NIH Rare Disease Day event, on Leap Day (Feb. 29), will feature patient’s voice and international collaboration
Why/What
On Feb. 29, NIH will host a Rare Disease Day event to raise awareness about rare diseases, the people they affect and current research collaborations. An estimated 25 million people in the United States have rare diseases. The event will feature presentations, posters, exhibits, an art show and tours of the NIH Clinical Center – a hospital at which researchers are studying nearly 600 rare diseases in partnership with over 30,000 patients. Admission is free and open to the public.Agenda: http://bit.ly/1JYUEQ3 (link is external)
Registration: http://bit.ly/1X45Z3d (link is external)
Watch the event live: https://videocast.nih.gov
Learn more: https://ncats.nih.gov/rdd
When/Where
February, 29, 20168:30 a.m. – 3:30 p.m.
NIH Clinical Center (Building 10) Masur Auditorium, 10 Center Dr., Bethesda, Maryland
Early stage primary ovarian mucinous carcinoma: Outcome-based clinicopathological study in comparison with serous carcinoma
open access
A major concern associated with ovarian mucinous carcinoma is the fact that metastatic carcinoma is much more common than primary tumours.6 Metastatic ovarian mucinous carcinomas may originate from the colorectal region, pancreas, biliary tract, appendix, stomach, uterine cervix or other primary sites.7 The prognosis is substantially different between metastatic and primary ovarian mucinous carcinoma,7 so the differential diagnosis between these carcinomas becomes a critical issue. Under most circumstances, this distinction can be attained via a combined analysis of pathological and clinical features, but it may be problematic if the extraovarian primary carcinoma is inconspicuous. Consequently, a considerable proportion of ovarian metastatic mucinous carcinomas are misdiagnosed as primary tumours.7continue reading open access
Sampling and Recruiting Community-Based Programs Using Community-Partnered Participation Research
abstract
The inclusion of community partners in participatory leadership roles around statistical design issues like sampling and randomization has raised concerns about scientific integrity. This article presents a case study of a community-partnered, participatory research (CPPR) cluster-randomized, comparative effectiveness trial to examine implications for study validity and community relevance. Using study administrative data, we describe a CPPR-based design and implementation process for agency/program sampling, recruitment, and randomization for depression interventions. We calculated participation rates and used cross-tabulation to examine balance by intervention status on service sector, location, and program size and assessed differences in potential populations served. We achieved 51.5% agency and 89.6% program participation rates. Programs in different intervention arms were not significantly different on service sector, location, or program size. Participating programs were not significantly different from eligible, nonparticipating programs on community characteristics. We reject claims that including community members in research design decisions compromises scientific integrity. This case study suggests that a CPPR process can improve implementation of a community-grounded, rigorous randomized comparative effectiveness trial.
Monday, February 15, 2016
Compassionate use of drugs and medical devices in the U.S., the European Union and Japan
open access
..... In this paper, we assess the current compassionate use, or expanded access-related mechanisms, of the US, the EU and Japan in regard to drugs, medical devices and biologics, including human cells and tissue products, and discuss the benefits and issues of these mechanisms. The purpose of these mechanisms is principally to save patients with life-threatening condition. However, the information obtained after the compassionate use is potentially useful to facilitate marketing authorization. In fact, the data from compassionate use cases are employed in some approval review reports to indicate the product safety.....
Conclusion
There
are various compassionate use-associated mechanisms for both drugs and
medical devices in the US and the EU. The main purpose of these
mechanisms is to save patients with life-threatening conditions with no
other approved alternative therapy options. Another important benefit
could be to provide safety and efficacy information to support future
market authorization. However, there are some cases in which companies
decline requests from patients to provide unapproved products because
they want to avoid the risk of the use of products before confirming
their efficacy and safety in clinical trials. In these cases, companies
are criticized for not providing the products to patients with
life-threatening conditions [31] and [32].
We propose comprehensive mechanisms that consider the risks and
benefits to the patients interested in using unapproved products and the
companies providing the products.
Conflicts of interest
Kenichiro Tsuyuki and Dr. Kazuo Yano are employees of Medtronic Japan Co., Ltd.
Dr. Masayuki Yamato is a shareholder of CellSeed Inc.
Keywords
- Compassionate use;
- Expanded access;
- Life-threatening;
- Serious disease;
- Clinical trial;
- Unapproved products
What Do You Mean by Medical Home? (editorial)
Editorial (requires subscription $$ to view in full)
16 February 2016
Ann Intern Med.
Keeping
up with the medical home is difficult. Researchers have published
dozens of studies on medical homes over the past few years, including an
article in this week's Annals by Kern and colleagues, and we
can expect dozens more. To complicate matters, these studies frequently
disagree with each other. Some have found that medical homes have modest
or no effects, whereas others have found desirable changes in quality,
utilization, and costs of care. The editorialist believes that to better
understand the contribution of each new medical home study, we must
first ask how the researchers defined “medical home.”
Topics
medical homeMuir-Torre syndrome (MTS): An update and approach to diagnosis and management
abstract
Muir-Torre syndrome (MTS) is a rare genetic condition that predisposes individuals to skin tumors and visceral malignancies. Because of the potentially aggressive nature of internal malignancies and sebaceous carcinoma, and the tendency to have multiple low-grade visceral cancers, close cancer surveillance is required in individuals and their families with this usually autosomal dominant disorder. Although the majority of MTS is caused by mutations in DNA mismatch repair genes resulting in microsatellite instability, a newly described subtype of MTS does not demonstrate microsatellite instability and may be inherited in an autosomal recessive pattern. In addition, MTS may be unmasked in transplant recipients taking specific immunosuppressant drugs or other immunosuppressed patients. Neoplasms may be subject to immunohistochemistry or both immunohistochemistry and genetic testing to confirm the diagnosis of MTS. Here, we offer an update and an approach to the diagnosis and management of MTS with a particular emphasis on the role of immunohistochemistry and genetic testing.
Key words
- immunohistochemistry;
- keratoacanthoma;
- Lynch syndrome;
- microsatellite instability;
- mismatch repair;
- Muir-Torre;
- sebaceous adenoma;
- sebaceous carcinoma;
- sebaceous epithelioma;
- sebokeratoacanthoma
Familial skin cancer syndromes: Increased risk of nonmelanotic skin cancers and extracutaneous tumors (eg. Lynch Syndrome, MTS)
abstract
Continuing medical education
- Refers To
Journal Based CME Instructions and Information
- Journal of the American Academy of Dermatology, Volume 74, Issue 3, March 2016, Page A42
- Journal of the American Academy of Dermatology, Volume 74, Issue 3, March 2016, Pages 452-453
Nonmelanoma skin cancers (NMSCs) represent the most common malignancies worldwide, with reported incidence rising each year. Both cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), as well as other NMSCs, represent complex diseases with a combination of environmental and genetic risk factors. In general, hereditary cancer syndromes that increase the risk of NMSC fall under several broad categories: those associated with immunodeficiencies, those that affect skin pigmentation, and those that perturb key molecular pathways involved in the pathogenesis of NMSCs. Many of the syndromes are also associated with extracutaneous manifestations, including internal malignancies; therefore, most require a multidisciplinary management approach with a medical geneticist. Finally, dermatologists play a critical role in the diagnosis and management of these conditions, because cutaneous findings are often the presenting manifestations of disease.
Key words
- Bloom syndrome;
- dyskeratosis congenita;
- genetic testing;
- Gorlin syndrome;
- Muir–Torre syndrome;
- nonmelanoma skin cancer;
- oculocutaneous albinism;
- Rothmund–Thomson syndrome;
- Werner syndrome
Abbreviations used
- 5-FU, 5-fluorouracil;
- ADA1, adenosine deaminase 1;
- ADA-SCID, adenosine deaminase severe combined immunodeficiency;
- BCC, basal cell carcinoma;
- BCNS, basal cell nevus syndrome;
- BDCS, Bazex-Dupré-Christol syndrome;
- BLM/RECQL3, Bloom syndrome, RecQ helicase-like;
- C10Orf11, chromosome 10 open reading frame 11;
- C16Orf57, chromosome 16 open reading frame 57;
- DFSP, dermatofibrosarcoma protuberans;
- DC, dyskeratosis congenita;
- EV, epidermodysplasia verruciformis;
- EVER1, epidermodysplasia verruciformis 1;
- EVER2, epidermodysplasia verruciformis 2;
- HNPCC, hereditary nonpolyposis colon cancer;
- HPV, human papillomavirus;
- IHC, immunohistochemistry;
- MMR, mismatch repair;
- MSI, microsatellite instability;
- MTS, Muir–Torre syndrome;
- MSSE, multiple self-healing squamous epithelioma;
- MLH1, MutL homolog 1;
- MSH2, MutS homolog 2;
- MSH6, MutS homolog 6;
- NK, natural killer;
- NMSC, nonmelanoma skin cancer;
- OCA, oculocutaneous albinism;
- OCA2, oculocutaneous albinism 2;
- PTCH1, patched1;
- PTCH2, patched2;
- PMS2, postmeiotic segregation increased 2;
- RECQL4, RecQ protein-like 4;
- RTS, Rothmund–Thomson syndrome;
- SMO, smoothened;
- SLC24A5, solute carrier family 24, member 5;
- SLC45A2, solute carrier family 45, member 2;
- SHH, sonic hedgehog;
- SCC, squamous cell carcinoma;
- SUFU, suppressor of fused gene;
- TGFBR1, transforming growth factor beta receptor 1;
- TYR, tyrosinase;
- TYRP1, tyrosinase-related protein 1;
- UVR, ultraviolet radiation;
- WRN/RECQL2, Werner syndrome, RecQ helicase-like;
- XP, xeroderma pigmentosum
Familial skin cancer syndromes: Increased melanoma risk (eg. brca)
abstract
Continuing medical education
Familial skin cancer syndromes : Increased melanoma risk
- Referred to by
CME examination
- Journal of the American Academy of Dermatology, Volume 74, Issue 3, March 2016, Page 435
Phenotypic traits, such as red hair and freckling, increase melanoma risk by 2- to 3-fold. In addition, approximately 10% of melanomas are caused by inherited germline mutations that increase melanoma risk from 4- to >1000-fold. This review highlights the key genes responsible for inherited melanoma, with an emphasis on when a patient should undergo genetic testing. Many genetic syndromes associated with increased melanoma risk are also associated with an increased risk of other cancers. Identification of these high-risk patients is essential for preventive behavior reinforcement, genetic counseling, and ensuring other required cancer screenings.
Key words
- genetics;
- genetic syndromes;
- inherited cancer risk;
- melanoma;
- oncogenes;
- skin cancer;
- tumor suppressor
Abbreviations used
- ACD, adrenocortical dysplasia homologue;
- BAP1, BRCA1-associated protein-1 (ubiquitin carboxy-terminal hydrolase);
- CDKN2A, cyclin-dependent kinase inhibitor 2A;
- CDK4, cyclin-dependent kinase 4;
- LFS, Li–Fraumeni syndrome;
- MM, malignant melanoma;
- MCR1, melanocortin 1 receptor;
- MITF, microphthalmia-associated transcription factor;
- POT1, protection of telomeres 1;
- PTEN, phosphatase and tensin homolog;
- TERT, telomerase reverse transcriptase;
- TERF2IP, telomeric repeat binding factor 2, interacting protein;
- UV, ultraviolet;
- XP, xeroderma pigmentosum
Risk factors for readmission in patients with ovarian, fallopian tube, and primary peritoneal carcinoma who are receiving front-line chemotherapy on a clinical trial (GOG 218)...
open access
Risk factors for readmission in patients with ovarian, fallopian tube, and primary peritoneal carcinoma who are receiving front-line chemotherapy on a clinical trial (GOG 218): an NRG oncology/gynecologic oncology group study (ADS-1236)☆......Patients with ovarian cancer represent a unique group of cancer patients, because they are treated with a combination of both extensive surgery and intensive combination chemotherapy. They therefore represent an important population to study with respect to avoiding unnecessary readmission. In order to strategize how to decrease readmissions and improve patient quality of care, it is imperative to first identify predictors of readmission. To date, most studies related to unplanned readmission of patients with advanced ovarian cancer have been limited to single institution studies with retrospective capture of data.....
Table 1 Characteristics of re-hospitalized patients.
Table 2 Hospitalized patients: medical history and surgical details.
Table 3 Rehospitalization toxicities.
Fifty-nine patients had 2 or more readmissions (Tables 4 and and 5).
read full text - open access
Sunday, February 14, 2016
Hereditary cancer syndromes: utilizing DNA repair deficiency as therapeutic target (BRCA/Lynch Syndrome0
full text - open access
eg. BRCA related ovarian cancer; DNA repair mechanisms....
This review article will discuss the latest therapeuticabstract
options in the major DNA repair deficient inherited cancer
syndromes, including hereditary non-polyposis colorectal
cancer (Lynch syndrome), and breast cancer susceptibility
gene (BRCA) associated ovarian and breast cancer.
Human cells have numerous repair mechanisms to counteract various insults incurred on the DNA. Any mutation in these repair mechanisms can lead to accumulation of DNA errors and carcinogenesis. This review aims to discuss the therapeutic options in the two most common DNA repair deficient cancer syndromes, namely Lynch syndrome (hereditary non-polyposis colorectal cancer) and breast cancer susceptibility gene (BRCA) associated ovarian and breast cancer. Deficiency in DNA repair mechanisms renders these tumors with increased sensitivity to platinum agents. There has been increasing amount of information on the utility of the defects in DNA repair as targets for cancer therapy in these syndromes.
In America, the art of doctoring is dying (Opinion)
Blogger's Note: think we can safely say this is not just a made-in-USA issue, fortunately there are exceptions
The Washington Post
Read more on this topic:
Michael Stein: When care is delivered in 15 minutes, there’s not much time for caring
Charles Krauthammer: Why doctors quit
Dan Morhaim: America’s electronic medical records mess
The immortal cells of Henrietta Lacks - Ted Ed (you tube)
Published on Feb 8, 2016
View full lesson: http://ed.ted.com/lessons/the-immorta...Imagine something small enough to float on a particle of dust that holds the keys to understanding cancer, virology, and genetics. Luckily for us, such a thing exists in the form of trillions upon trillions of human, lab-grown cells called HeLa. But where did we get these cells? Robin Bulleri tells the story of Henrietta Lacks, a woman whose DNA led to countless cures, patents, and discoveries. http://ovariancancerandus.blogspot.com/feeds/posts/default
Chemotherapy in ovarian germ cell tumors: A systematic review
abstract
OBJECTIVE:
Ovarian germ cell tumors (OGCTs) are rare tumors that comprise a diverse group of histologic subtypes that can either be benign or malignant. Malignant ovarian germ cell tumors (OGCTs) historically carried a poor prognosis, especially among those diagnosed with advanced disease. With the advent of combination chemotherapy, risk of relapse has markedly decreased. There is limited prospective data on the efficacy of specific chemotherapy regimens in the treatment of malignant OGCTs. This article critically reviews the literature pertinent to the treatment of OGCTs with chemotherapy.METHODS:
MEDLINE was searched for English language literature on prospective studies on the treatment of malignant OGCTs, focusing on publications since 1995.RESULTS:
As modern chemotherapy regimens have evolved, risk of relapse has decreased with implementation of platinum based regimens in the adjuvant setting. However, the role of neoadjuvant platinum based regimens and treatment of metastatic or recurrent malignant OGCTs remains poorly understood due to lack of randomized control trials.CONCLUSIONS:
Malignant OGCTs represent a rare subset of ovarian neoplasms for which focused, prospective clinical trials are needed to determine the most effective therapies.Prevalence of pelvic floor disorders in women with suspected gynecological malignancy: a survey-based study
abstract
INTRODUCTION AND HYPOTHESIS:
Understanding of pelvic floor disorders among women with gynecological cancer is limited. The objective of this study was to describe the prevalence of pelvic floor disorders in women with suspected gynecological malignancy before surgery.METHODS:
A cross-sectional study was performed of women aged ≥18 with a suspected gynecological malignancy who enrolled in the University of North Carolina Health Registry/Cancer Survivorship Cohort (HR/CSC) from August 2012 to June 2013. Demographics were obtained from the HR/CSC self-reported data; clinical data were abstracted from the electronic medical record. Subjects completed validated questionnaires (Rotterdam Symptom Checklist and the International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms) to assess bladder and bowel function.RESULTS:
Among 186 women scheduled for surgery for gynecological malignancy, 152 (82 %) completed baseline assessments before surgery. Mean age was 58.1 ± 13.3 years, and mean BMI was 33.6 ± 8.8 kg/m2. The majority of subjects had uterine cancer (61.8 %), followed by ovarian (17.1 %) and cervical (11.1 %). At baseline, the rate of urinary incontinence (UI) was 40.9 %. A third of subjects reported stress UI, and one quarter reported urge UI. The overall rate of fecal incontinence was 3.9 %, abdominal pain was 47.4 %, constipation was 37.7 %, and diarrhea was 20.1 %. When comparing cancer types, there were no differences in pelvic floor symptoms.CONCLUSION:
Pelvic floor disorders are common in women with suspected gynecological malignancy at baseline before surgery. Recognizing pelvic floor disorders in the preoperative setting will allow for more individualized, comprehensive care for these women.Trends in anemia treatment among patients.....
abstract
Trends in anemia treatment among patients with five non-myeloid malignancies treated with chemotherapy in a large integrated health care delivery system in California, 2000-2013
PURPOSE:
The aim of this study is to examine treatment patterns for chemotherapy-induced anemia (CIA) between calendar periods when the changes in the US prescribing information, for erythropoiesis-stimulating agents (ESAs) took place.METHODS:
Patients diagnosed with breast, lung, colorectal, ovarian, or gastric cancer (2000-2012) who developed grade 2+ CIA (hemoglobin (Hb) <10 g/dl) were identified from Kaiser Permanente Southern California Health Plan. We estimated the proportions of CIA episodes with ESA use, red blood cell (RBC) transfusion, or prescription nutritional supplements in three calendar periods: January 1, 2000-December 31, 2006 (P1), January 1, 2007-March 24, 2010 (P2), and March 25, 2010-June 30, 2013 (P3).....Saturday, February 13, 2016
Predicting the risk of malignancy in adnexal masses based on the Simple Rules....
abstract: Predicting the risk of malignancy in adnexal masses based on the Simple Rules from the International Ovarian Tumor Analysis (IOTA) group
BACKGROUND:
Accurate methods to preoperatively characterize adnexal tumors are pivotal for optimal patient management. A recent meta-analysis concluded that the International Ovarian Tumor Analysis (IOTA) algorithms such as the Simple Rules are the best approaches to preoperatively classify adnexal masses as benign or malignant.OBJECTIVE:
To develop and validate a model to predict the risk of malignancy in adnexal masses using the ultrasound features in the Simple Rules.Triple peptide vaccination as consolidation treatment in women affected by ovarian and breast cancer
abstract
Triple peptide vaccination as consolidation treatment in women affected by ovarian and breast cancer: Clinical and immunological data of a phase I/II clinical trial
In this phase I/II study, 14 high-risk disease-free ovarian (OC) and breast cancer (BC) patients after completion of standard therapies were vaccinated with MUC1, ErbB2 and carcinoembryonic antigen (CEA) HLA-A2+-restricted peptides and Montanide.....
......In particular OC patients appear to show a higher response rate compared to BC patients. Vaccination generates a long-lasting immune response, which is strongly enhanced by recall administrations. The clinical outcome of patients enrolled in the trial appears favourable, having registered no deceased patients with a minimum follow-up of 8 years. These promising data, in line with the results of similar studies, the high compliance of patients observed and the favourable toxicity profile, support future trials of peptide vaccination in clinically disease-free patients who have completed standard treatments.
Does VEGF facilitate local tumor growth and spread into the abdominal cavity....
abstract
Does VEGF facilitate local tumor growth and spread into the abdominal cavity by suppressing endothelial cell adhesion, thus increasing vascular peritoneal permeability followed by ascites production in ovarian cancer?
CONCLUSIONS:
Our results indicate that increased peritoneal permeability in ovarian cancer is due to down-regulation of adhesion proteins via tumor derived VEGF. Advanced ovarian cancer with aggressive tumor biology may be associated with early dysregulation of vascular permeability leading to ascites. These patients may benefit from therapeutic VEGF inhibition.
Survey Shows People Want to Collaborate with Their Doctors and Co-Produce Their Clinical Data
e-Patients.net
Evidence! New S4PM Survey Shows People Want to Collaborate with Their Doctors and Co-Produce Their Clinical Data
So it was quite gratifying to see the results of a new Society for Participatory Medicine survey. The survey, fielded by ORC International, a professional survey firm, asked 1000 adults five questions. We’re publishing the results in this downloadable PDF infographic
The Passive Patient and Disclosure of Genetic Information: Can English Tort Law Protect the Relatives’ Right to Know?
abstract
The Passive Patient and Disclosure of Genetic Information: Can English Tort Law Protect the Relatives’ Right to Know?
Despite the extensive literature on disclosure of genetic information to family members, this area remains topical and attracts scholarly debate. This derives from the general understanding that informing relatives can help them reduce the risk of developing a genetic disease. The scholarly debate in law and bioethics mainly focuses on patients’ explicit refusal to inform relatives. However, this article examines the common phenomenon of passive non-disclosure where patients agree to share genetic test results with their relatives in principle but refrain from doing so in practice. Analysing the position of English tort law leads the author to conclude that it can and should impose legal liability on patients to alert relatives that there is genetic information they can pursue. It is suggested that if the goals are to enable family members to avoid harm and make autonomous decisions about health, English tort law should adopt a communitarian position and support the models of communication used in practice by clinicians in genetics.
Association and prognostic significance of BRCA1/2-mutation status....PD-1/PD-L1
Abstract
Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer
These findings support a link between BRCA1/2-mutation status, immunogenicity and survival, and suggesting that BRCA1/2-mutated HGSOCs may be more sensitive to PD-1/PD-L1 inhibitors compared to HR-proficient HGSOCs.
Update on Lynch syndrome genomics (InSiGHT)
open access
This review provides an update of germline mutations causing susceptibility to LS based on information available in the InSiGHT database and the latest literature.
MLH1, MSH2, MSH6 and PMS2 account for 40, 34, 18, and 8 %, respectively, of the 3000 unique germline sequence variants of MMR genes deposited to the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) database ([16] and www.insight-group.org, date accessed December 19th, 2015).
Lynch Syndrome Screening in the Gynecologic Tract: Current State of the Art
abstract
Lynch syndrome underlies approximately 5% of endometrial cancers and ~1% of ovarian cancers. Gynecologic malignancies are often the presenting cancer in these patients. Therefore, there is considerable benefit to identifying these patients and enrolling them and affected family members in surveillance programs for secondary malignancies. The molecular basis for Lynch syndrome is a defect in the DNA mismatch repair (MMR) system. Tumors can be screened for these defects using immunohistochemistry to identify loss of MMR proteins or by enlisting polymerase chain reaction to identify the microsatellite instability that attends dysfunctional MMR. However, diagnostic confirmation of Lynch syndrome requires germline mutational testing. The algorithm for screening endometrial carcinomas for Lynch syndrome remains a subject of debate, with some studies supporting universal screening and others proposing a hybrid approach informed by clinicopathologic features. This review discusses the rationales and relative merits of current Lynch syndrome-screening approaches for endometrial and ovarian cancers and provides pathologists with an informed approach to Lynch syndrome testing in gynecologic cancers. It also addresses the clinical difficulties presented by cases with discordant screening and germline results (Lynch-like cancers) and emphasizes the critical role of strong communication with clinician and genetic counseling colleagues to ensure that the significance of a positive screening test is appropriately conveyed to patients. Finally, it discusses the need for more nuanced cost-effective analyses and the potential role for next-generation sequencing panels in future screening efforts.
Friday, February 12, 2016
Multiple neoplasms, single primaries, and patient survival
Blogger's Note: references data from numerous countries
open access (published 2014)
(single blinded retrospective study) Between 2005 and 2012, of 1,873 cancer patients, 322 developed second malignancies....
The best survival was for patients with three or more primaries (median 10.9 years)......
Such an entity of multiple neoplasms is not rare or new, being described by Billroth as far back as 1889.1
It has been suggested that, in patients with familial cancer syndrome, the risk of a second primary is approximately 3% for each year of survival after the first cancer occurrence.
Practically all types of hereditary cancers showed an excess of multiple primaries as well as an early age of onset.22,24,27,28,31–33,36 It has been suggested that abnormal genes or gene variants might be responsible for the clustering observed with some tumors.
In the present study, a strong family history of cancer reflecting a close relationship between first-degree relatives was statistically more common in patients with multiple primaries, especially those with three or more primaries, and in those with metachronous primaries, highly suggestive of inherited cancer predisposition gene mutations, especially among Caucasian patients.....Background: Multiple primary neoplasms in surviving cancer patients are relatively common, with an increasing incidence. Their impact on survival has not been clearly defined.
Conclusion: Patients with multiple primaries are usually of Caucasian ancestry, have less aggressive malignancies, present at earlier stages, frequently have a strong family history of similar cancer, and their cancers tend to have indolent clinical behavior with longer survival rates, possibly related to genetic predisposition.
Table 4 Risk of developing multiple primaries in cancer patients relative to initial primary site and initial cancer staging
Differentiation of epithelial ovarian cancer subtypes by use of imaging and clinical data: a detailed analysis
open access (Japan)
The purpose of this study was to study whether we can determine subtypes of epithelial ovarian cancer by using computed tomography (CT) and magnetic resonance imaging (MRI) with the clinical findings, including the tumor marker and paraneoplastic syndrome such as venous thrombosis or hypercalcemia, to support NAC (neoadjuvant chemotherapy).
(PDS+primary debulking surgery)
Table 1
Patients Population
Histopathologic Subtypes
|
Age (years old)
|
Treatment
|
Total Number of Cases
| |
|---|---|---|---|---|
PDS
|
NAC
| |||
Serous
|
61 (31–85)
|
24
|
20
|
44
|
Mucinous
|
59 (37–84)
|
12
|
1
|
13
|
Clear cell
|
57 (37–81)
|
51
|
2
|
53
|
Endometrioid
|
59 (43–84)
|
15
|
0
|
15
|
Total
|
59 (31–85)
|
102
|
23
|
125
|
CA125 (mean, U/ml)
|
2081.6
|
225.6
|
683.6
|
1936.5
| |
Some limitations in our study should be pointed out. First, we could analyze only the morphological characteristics of the ovarian carcinomas, whereas numerous histological types of tumors affect the ovaries. Therefore, the process of differential diagnosis in daily practice may be more complex. Second, the number of tumors that we analyzed was limited. We included relatively larger number of CCC as our study population included a lot of ovarian cancer coexisting endometriosis. However, a bigger number of tumors need to be analyzed, in particular MC and EC.
Canadian drug price gouging for generics called 'hard to celebrate' (11 country comparison)
CBC
Canadians spend extra $1 billion a year compared with other industrialized countries....
In 2010, Canadian prices were 40 per cent higher than in 11 industrialized countries: France, Germany, Italy, Sweden, Switzerland, the United Kingdom, the United States, the Netherlands, Spain, Australia, and New Zealand.
SATB2 Expression Distinguishes Ovarian Metastases of Colorectal and Appendiceal Origin From Primary Ovarian Tumors of Mucinous or Endometrioid Type
abstract
The primary origin of some ovarian mucinous tumors may be challenging to determine, because some metastases of extraovarian origin may exhibit gross, microscopic, and immunohistochemical features that are shared by some primary ovarian mucinous tumors. Metastases of primary colorectal, appendiceal, gastric, pancreatic, and endocervical adenocarcinomas may simulate primary ovarian mucinous cystadenoma, mucinous borderline tumor, or mucinous adenocarcinoma. Recently, immunohistochemical expression of SATB2, a transcriptional regulator involved in osteoblastic and neuronal differentiation, has been shown to be a highly sensitive marker of normal colorectal epithelium and of colorectal adenocarcinoma. SATB2 expression has not been reported in normal epithelium of the female reproductive tract. Therefore, we hypothesized that SATB2 may be of value in distinguishing ovarian metastases of colorectal adenocarcinoma from primary ovarian mucinous tumors and from primary ovarian endometrioid tumors.
Invasion Patterns of Metastatic Extrauterine High-grade Serous Carcinoma With BRCA Germline Mutation and Correlation With Clinical Outcomes
abstract
Invasion Patterns of Metastatic Extrauterine High-grade Serous Carcinoma With BRCA Germline Mutation and Correlation With Clinical Outcomes
Characteristic histopathologic features have been described in high-grade serous carcinoma associated with BRCA abnormalities (HGSC-BRCA), which are known to have relatively favorable clinical outcomes. The aim of this study was to evaluate the clinical significance of invasion patterns in metastatic HGSC-BRCA cases. Of the 37 cases of advanced-stage HGSC with known BRCA1 or BRCA2 germline mutation retrieved from our institutional files, 23 patients had a germline mutation of BRCA1 and 14 had a BRCA2 mutation. The pattern of invasion at metastatic sites was recorded and classified as a pushing pattern (either predominantly or exclusively), an exclusively micropapillary infiltrative pattern, or an infiltrative pattern composed of papillae, micropapillae, glands, and nests (mixed infiltrative pattern). Histologic evaluation of metastases was performed without knowledge of genotype or clinical outcome. Clinical data were abstracted from medical records. Median age was 56 years (range, 31 to 73 y).
Loss of SMARCA4 Expression Is Both Sensitive and Specific for the Diagnosis of Small Cell Carcinoma of Ovary, Hypercalcemic Type
abstract
Loss of SMARCA4 Expression Is Both Sensitive and Specific for the Diagnosis of Small Cell Carcinoma of Ovary, Hypercalcemic Type
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare ovarian neoplasm that occurs in young women
Morphological and Immunohistochemical Reevaluation of Tumors Initially Diagnosed as Ovarian Endometrioid Carcinoma...
abstract
Morphological and Immunohistochemical Reevaluation of Tumors Initially Diagnosed as Ovarian Endometrioid Carcinoma With Emphasis on High-grade Tumors
Ovarian endometrioid carcinomas (OEC) of low grade have characteristic morphologic features, but high-grade tumors can mimic high-grade serous and undifferentiated carcinomas. We reviewed tumors initially diagnosed as OEC to determine whether a combination of pathologic and immunohistochemical features can improve histologic subclassification. Tumors initially diagnosed as OEC were reviewed using World Health Organization criteria. We also noted the presence of associated confirmatory endometrioid features (CEFs): (i) squamous metaplasia; (ii) endometriosis; (iii) adenofibromatous background; and (iv) borderline endometrioid or mixed Mullerian component. A tissue microarray was constructed from 27 representative tumors with CEF and 14 without CEF, and sections were stained for WT-1, p16, and p53. Of 109 tumors initially diagnosed as OEC, 76 (70%) tumors were classified as OEC. The median patient age was 55 years, and 75% of patients were younger than 60 years. Ninety-two percent presented with disease confined to the pelvis, and 87% of tumors were unilateral. The median tumor size was 11.8 cm. Only 3% of tumors were high grade (grade 3of 3). Eighty percent of cases had at least 1 CEF, and 59% had at least 2 CEFs. Eleven percent overexpressed p16, 0% overexpressed p53, and 3% expressed WT-1. Only 10% of patients died of disease at last follow-up. Thirty-three (33) tumors, or 30% of tumors originally classified as endometrioid, were reclassified as serous carcinoma (OSC). The median patient age was 54.5 years, and 59% of patients were younger than 60 years of age. Only 27% had disease confined to the pelvis at presentation, 52% of tumors were unilateral, and the median tumor size was 8 cm. Associated squamous differentiation, endometrioid adenofibroma, and endometrioid or mixed Mullerian borderline tumor (CEFs) were not present in any case, but 6% of patients had endometriosis. Approximately one half of the reclassified OSC demonstrated SET-pattern morphology (combinations of glandular, cribriform, solid, and transitional cell–like architecture) and were immunophenotypically indistinguishable from OSCs with papillary architecture. Sixty percent of OSC overexpressed p16, 50% overexpressed p53, and 82% expressed WT-1. At last follow-up, 52% had died of disease. Compared with OSC, OEC patients more frequently presented below 60 years of age (P=0.046), had low-stage tumors (P<0.001), were more frequently unilateral (P<0.001), more frequently had synchronous endometrial endometrioid carcinomas (P<0.001); and had no evidence of disease at last follow-up (P<0.001). Their tumors were of lower grade (P<0.001), had more CEFs (P<0.001), and less frequently overexpressed p16 and p53 (P=0.003 and P<0.001, respectively) and less frequently expressed WT-1 (P<0.001). This analysis emphasizes the diagnostic value of CEFs, the presence of a low-grade gland-forming endometrioid component, and WT-1 negativity, as valid, clinically relevant criteria for a diagnosis of OEC. Glandular and/or cribriform architecture alone may be seen in both OECs and OSCs and are therefore not informative of diagnosis. Further study is needed to elaborate the characteristics of the exceedingly rare high-grade OEC.
Financial Insolvency May Be a Risk Factor for Early Mortality Among Patients With Cancer
Extreme financial distress appeared to influence survival after cancer diagnosis and may be taking a greater toll on patients than previously recognized, Seattle researchers have found.1.....
“Oncologists need to be mindful that their patients may have a tenuous financial situation that could prevent them from completing planned therapies,” said study investigator Scott Ramsey, MD, PhD, director of the Hutchinson Institute for Cancer Outcomes Research at the Fred Hutchinson Cancer Center in Seattle, WA, in an interview with Cancer Therapy Advisor.
Vinay Prasad, MD, MPH, assistant professor of medicine at the Oregon Health & Science University Knight Cancer Institute in Portland, said this is becoming a greater concern than ever before.
“We are already thinking about biological toxicity, and now we have to think about a whole new class of toxicity. We have to deal with these toxicities and no longer ignore them,” Dr Prasad told Cancer Therapy Advisor.
Editorial: Liquid cancer biopsy: the future of cancer detection? (Grail)
Editorial: The Lancet Oncology
This year's JP Morgan Annual Healthcare Conference (Jan 11–15, 2016) in San Francisco, CA, USA, saw the announcement of a new biotechnology company called Grail—a spinoff from Illumina (San Diego, CA, USA; one of the world's largest diagnostics companies). Chaired by the Illumina Chief Executive Officer Jay Flatley, and with a science advisory board headed by José Baselga (Memorial Sloan Kettering Cancer Center, New York, NY, USA), Grail declared its mission to be “the early detection of cancer in asymptomatic individuals through a blood screen”. Flatley's aim is to deliver this ambitious pan-tumour test in just 3 years. The notion of cancer detection by liquid biopsy is not a new concept: indeed, many other companies are also developing blood-based tests to monitor cancer progression or screen high-risk asymptomatic individuals. However, such tests to date have focused on specific cancer types, rather than a single test to detect all aysmptomatic cancers based on circulating tumour DNA (ctDNA). Is this objective possible? And what are the wider implications for patients with cancer?....
Grail's endeavour, however, is laudable in its ambitious scope, and it will be fascinating to watch over the coming years whether the company achieves its objective.
Differing Perspectives on Breast Cancer Chemoprevention—Reply/Debates (Letters)
JAMA Oncology (Narod)
Differing Perspectives on Breast Cancer Chemoprevention
Jack Cuzick, PhD; Larry Wickerham, MD; Trevor Powles, MD
Differing Perspectives on Breast Cancer Chemoprevention
V. Craig Jordan, OBE, PhD, DSc, FMedSci
Clarifying Assumptions and Outcomes in Cost-effectiveness Analyses
Kevin ten Haaf, MSc; Harry J. de Koning, MD, PhD
Differing Perspectives on Breast Cancer Chemoprevention—Reply
Steven A. Narod, MD
Clarifying Assumptions and Outcomes in Cost-Effectiveness Analyses—Reply
John R. Goffin, MD, FRCPC; William M. Flanagan, BM; William K. Evans, MD, FRCPC
Editor's Note
Editorial: For Patients With Cancer, Cure Is Not Enough
JAMA (full access requires $$)
Advances in cancer therapy have led to increased survival; there are more than 9 million 5-year survivors of cancer in the United States.1 As this number continues to grow, focus on improved health and quality of life becomes a priority. It is especially important in survivors of childhood, adolescent, and young adult cancer who have 5-year survival rates exceeding 80%1 and who are expected to live many decades after diagnosis and treatment. Because of their young age at treatment, this population is the most vulnerable to long-term detrimental effects of cancer therapy. Many studies have shown that childhood and adolescent cancer survivors are at increased risk for chronic medical problems and emotional late effects as they age.2- 5 These late effects influence overall health and quality of life.
JAMA: Incomplete Conflict of Interest Disclosure (Utilization and Outcomes of BRCA Genetic Testing and Counseling in a National Commercially Insured Population: The ABOUT Study)
Incomplete Conflict of Interest Disclosure
A correction has been published | View article
REFERENCES
Armstrong
J, Toscano
M, Kotchko
N,
et al. Utilization and outcomes of BRCA genetic testing and counseling in a national commercially insured population: the ABOUT Study . JAMA Oncol. 2015;1(9):1251-1260.
PubMed | Link to Article
PubMed | Link to Article
Somatic Mosaic Mutations in PPM1D and TP53 in the Blood of Women With Ovarian Carcinoma
abstract
In contrast, somatic mosaic mutations in TP53 were not significantly associated with chemotherapy or age.
Conclusions and Relevance Chemotherapy exposure and age influence the accumulation of PPM1D-mutated PBMC (peripheral blood mononuclear cells) clones. Care should be taken to control for chemotherapy exposure and age at blood draw when testing the association of somatic mosaic mutations in PBMCs with cancer risk.
Increased Reach of Genetic Cancer Risk Assessment as a Tool for Precision Management of Hereditary Breast Cancer
JAMA Network - Editorial (open access)
It is disconcerting that 48% of those who did not get testing indicated that they and/or their physician did not think a BRCA mutation was likely, despite the fact that the National Comprehensive Cancer Network (NCCN) guideline2 has recommended genetic counseling and BRCA testing for women with breast cancer diagnosed at 40 years or younger since the outset of the YWS study.
BRCA1 and BRCA2 Mutation Testing in Young Women With Breast Cancer FREE
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