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Tuesday, February 13, 2018

open access Feb 13, 2018: The Yet Unrealized Promise of Ovarian Cancer Screening

The Yet Unrealized Promise of Ovarian Cancer Screening



US Preventive Services Task Force.  Screening for ovarian cancer: US Preventive Services Task Force recommendation statement  [published February 13, 2018].  JAMA. doi:10.1001/jama.2017.21926Google Scholar
Henderson  JT, Webber  EM, Sawaya  GF.  Screening for ovarian cancer: updated evidence report and systematic review for the US Preventive Services Task Force  [published February 13, 2018].  JAMA. doi:10.1001/jama.2017.21421Google Scholar
Jacobs  IJ, Menon  U, Ryan  A,  et al.  Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).  Lancet. 2016;387(10022):945-956.PubMedGoogle ScholarCrossref
Buys  SS, Partridge  E, Black  A,  et al; PLCO Project Team.  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.PubMedGoogle ScholarCrossref
Jacobs  IJ, Skates  SJ, MacDonald  N,  et al.  Screening for ovarian cancer: a pilot randomised controlled trial.  Lancet. 1999;353(9160):1207-1210.PubMedGoogle ScholarCrossref
Barrett  J, Jenkins  V, Farewell  V,  et al; UKCTOCS trialists.  Psychological morbidity associated with ovarian cancer screening: results from more than 23,000 women in the randomised trial of ovarian cancer screening (UKCTOCS).  BJOG. 2014;121(9):1071-1079.PubMedGoogle ScholarCrossref
American College of Obstetricians and Gynecologists (ACOG) Committee on Gynecologic Practice; Society of Gynecologic Oncology. ACOG Committee opinion No. 716, September 2017. https://www.acog.org/Clinical-Guidance-and-Publications/Committee-Opinions/Committee-on-Gynecologic-Practice/The-Role-of-the-Obstetrician-Gynecologist-in-the-Early-Detection-of-Epithelial-Ovarian-Cancer-in. Accessed January 22, 2018.
Marchetti  C, De Felice  F, Palaia  I,  et al.  Risk-reducing salpingo-oophorectomy: a meta-analysis on impact on ovarian cancer risk and all-cause mortality in BRCA 1 and BRCA 2 mutation carriers.  BMC Womens Health. 2014;14:150.PubMedGoogle ScholarCrossref
Rosenthal  AN, Fraser  LSM, Philpott  S,  et al; United Kingdom Familial Ovarian Cancer Screening Study collaborators.  Evidence of stage shift in women diagnosed with ovarian cancer during phase II of the UK Familial Ovarian Cancer Screening Study.  J Clin Oncol. 2017;35(13):1411-1420.PubMedGoogle ScholarCrossref
Skates  SJ, Greene  MH, Buys  SS,  et al.  Early detection of ovarian cancer using the Risk of Ovarian Cancer Algorithm with frequent CA125 testing in women at increased familial risk.  Clin Cancer Res. 2017;23(14):3628-3637.PubMedGoogle ScholarCrossref
Karlan  BY, Thorpe  J, Watabayashi  K,  et al.  Use of CA125 and HE4 serum markers to predict ovarian cancer in elevated-risk women.  Cancer Epidemiol Biomarkers Prev. 2014;23(7):1383-1393.PubMedGoogle ScholarCrossref
Menon  U, McGuire  AJ, Raikou  M,  et al.  The cost-effectiveness of screening for ovarian cancer: results from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).  Br J Cancer. 2017;117(5):619-627.PubMedGoogle ScholarCrossref
Sieh  W, Salvador  S, McGuire  V,  et al; Australian Cancer Study (Ovarian Cancer); Australian Ovarian Cancer Study Group; Ovarian Cancer Association Consortium.  Tubal ligation and risk of ovarian cancer subtypes.  Int J Epidemiol. 2013;42(2):579-589.PubMedGoogle ScholarCrossref
Garcia  C, Martin  M, Tucker  LY,  et al.  Experience with opportunistic salpingectomy in a large, community-based health system in the United States.  Obstet Gynecol. 2016;128(2):277-283.PubMedGoogle ScholarCrossref
Powell  CB, Swisher  EM, Cass  I,  et al.  Long-term follow-up of BRCA1 and BRCA2 mutation carriers with unsuspected neoplasia identified at risk reducing salpingo-oophorectomy.  Gynecol Oncol. 2013;129(2):364-371.PubMedGoogle ScholarCrossref
Labidi-Galy  SI, Papp  E, Hallberg  D,  et al.  High grade serous ovarian carcinomas originate in the fallopian tube.  Nat Commun. 2017;8(1):1093.PubMedGoogle ScholarCrossref

Friday, January 27, 2017

Cancer Network(2) Lynch Syndrome Associated Ovarian Cancer/Endometrioid/Serous Carcinoma

Cancer Network

Lynch Syndrome-Associated Ovarian Cancer Presents Early, Has Good Prognosis
An analysis of Lynch syndrome-associated ovarian cancer found that the malignancy tends to present at an early stage and has a generally good prognosis. Read More »
Endometrioid Ovarian Cancer Presents Earlier, Offers Better Survival Than Serous Carcinoma
Women with endometrioid ovarian cancer present at a younger age and with earlier stage disease than those with serous ovarian cancer, according to a new analysis. The earlier presentation resulted in better 5- and 10-year overall survival rates as well. Read More »

Feb 6th Webinar: Looking Ahead: Ovarian Cancer Advocacy in 2017

Looking Ahead: Ovarian Cancer Advocacy in 2017

Ovarian Cancer Advocacy Update: What You Need to Know
Monday, February 6 at 6pm Eastern (Webinar is Free)
With a new Congress and a new President, where do we stand with issues that impact the ovarian cancer community? 

Join OCRFA's Vice President of Policy, Chad Ramsey, for an important policy update webinar with a Q&A afterwards. 

Chad will be updating us about potential changes to healthcare policy, the status of biomedical research, and OCRFA's proactive policy agenda for 2017. 

You won't want to miss this. Can't make the live presentation? Sign up - all registrants will receive a link to the recorded presentation when it's available.

Newly released 2017 Canadian Nonprofit Sector Salary & Benefits Report reveals current compensation trends

Newly released 2017 Canadian Nonprofit Sector Salary & Benefits Report reveals current compensation trends

Cash compensation continues to grow slowly for many

Average cash compensation increased in the nonprofit sector, except for front-line and support staff, between 2013 and 2016. When increases were received, the majority were less than 3%. The most significant increase was among management/supervisory staff at a cumulative 15% since 2013. This growth will need to be monitored to determine if it is a trend or a temporary spike.

OA: Mesh, graft, or standard repair for women having primary transvaginal anterior or posterior compartment prolapse surgery...

Mesh, graft, or standard repair for women having primary transvaginal anterior or posterior compartment prolapse surgery: two parallel-group, multicentre, randomised, controlled trials (PROSPECT) - The Lancet


Augmentation of a vaginal repair with mesh or graft material did not improve women's outcomes in terms of effectiveness, quality of life, adverse effects, or any other outcome in the short term, but more than one in ten women had a mesh complication. Therefore, follow-up is vital to identify any longer-term potential benefits and serious adverse effects of mesh or graft reinforcement in vaginal prolapse surgery.

Familial Cancer journal January Index (not an OA publication)

Familial Cancer

(Seromucinous) Morphologic Reproducibility, Genotyping, and Immunohistochemical Profiling Do Not Support a Category of Seromucinous Carcinoma of the Ovary

Morphologic Reproducibility, Genotyping, and Immunohistochemical Profiling Do Not Support a Category of Seromucinous Carcinoma of the Ovary

The 2014 World Health Organization Classification of Tumors of Female Reproductive Organs endorsed the new category of seromucinous carcinoma, a neoplasm that exhibits morphologic and immunophenotypic overlap with other histotypes of ovarian carcinoma. The goal of this study was to determine whether seromucinous carcinoma was a distinct histotype by assessing its diagnostic reproducibility and comparing its molecular composition to the 5 major histotypes of ovarian carcinoma. Thirty-two tumors diagnosed as seromucinous carcinomas from 2 centers were studied. Eighteen cases were randomly selected for a review set comprising a total of 50 ovarian carcinomas of various histotypes. Morphologic histotype was independently assessed by 4 pathologists. For the 32 seromucinous carcinomas, a histotype-specific immunophenotype was assigned using a diagnostic immunohistochemical panel. Histotype-specific genotype was assigned using a combination of immunohistochemistry and targeted next-generation sequencing for somatic mutations, including genes recurrently mutated in ovarian carcinomas. There was low to modest agreement between pathologists with the reference diagnosis of seromucinous carcinoma, ranging from 39% to 56% for the 4 observers. The immunophenotype was not unique but overlapped predominantly with endometrioid and to a lesser extent with mucinous and low-grade serous carcinoma. Genomic and immunohistochemical alterations were detected in a number of target genes, including KRAS (70%), PIK3CA (37%), PTEN (19%), and ARID1A (16%); no CTNNB1 mutations were identified. Nine cases (30%) harbored concurrent KRAS/PIK3CA mutations. An endometrioid genotype was assigned to 19 cases, a low-grade serous genotype to 9, and a mucinous genotype to 1 and 3 cases were uninformative. Integrating morphology, immunophenotype, and genotyping resulted in reclassifying the seromucinous carcinomas to endometrioid 23/32 (72%), low-grade serous 8/32 (25%), and mucinous 1/32 (3%). The morphologic diagnosis of seromucinous carcinomas is not very reliable and it does not exhibit a distinct immunophenotype or genotype. The molecular features overlap mostly with endometrioid and low-grade serous carcinomas. Our data suggest the category of seromucinous carcinoma be discontinued as ancillary molecular tests can assign cases to one of the major histotypes.

Thursday, January 26, 2017

Systematic pan-cancer analysis reveals immune cell interactions in the tumor microenvironment

abstract AACR Cancer Research

 With the recent advent of immunotherapy, there is a critical need to understand immune cell interactions in the tumor microenvironment in both pan-cancer and tissue-specific contexts. Multi-dimensional datasets have enabled systematic approaches to dissect these interactions in large numbers of patients, furthering our understanding of the patient immune response to solid tumors. Using an integrated approach, we infered the infiltration levels of distinct immune cell subsets in 23 tumor types from The Cancer Genome Atlas. From these quantities, we constructed a co-infiltration network, revealing interactions between cytolytic cells and myeloid cells in the tumor microenvironment. By integrating patient mutation data, we show that while mutation burden was associated with immune infiltration differences between distinct tumor types, additional factors may explain immunogenic differences between tumors originating from the same tissue. Finally, we examined the prognostic value of individual immune cell subsets as well as how co-infiltration of functionally discordant cell types associated with patient survival. We showed in multiple tumor types that the protective effect of CD8+ T cell infiltration was heavily modulated by co-infiltration of macrophages and other myeloid cell types, suggesting the involvement of myeloid-derived suppressor cells in tumor development. Our findings illustrate complex interactions between different immune cell types in the tumor microenvironment and indicate these interactions play meaningful roles in patient survival. These results demonstrate the importance of personalized immune response profiles when studying the factors underlying tumor immunogenicity and immunotherapy response.

SWOG Launches National Immunotherapy Clinical Trial for Rare Cancers - The ASCO Post

  Surveillance, Epidemiology, and End Results Program

Number of New Cases and Deaths per 100,000: The number of new cases of ovarian cancer was 11.9 per 100,000 women per year. The number of deaths was 7.5 per 100,000 women per year. These rates are age-adjusted and based on 2009-2013 cases and deaths.
 Lifetime Risk of Developing Cancer: Approximately 1.3 percent of women will be diagnosed with ovarian cancer at some point during their lifetime, based on 2011-2013 data.
The ASCO Post
The trial is called DART (Dual Anti–CTLA-4 and Anti­–PD-1 Blockade in Rare Tumors) and is managed by SWOG, the cancer clinical trials group that is part of the National Cancer Institute’s (NCI) National Clinical Trials Network (NCTN). The trial is sponsored by the NCI and being conducted under the NCI collaborative agreements with Bristol-Myers Squibb for ipilimumab (Yervoy) and nivolumab (Opdivo).

The trial draws on the design and takes advantage of the scale of another landmark trial offered through the NCTN, NCI-MATCH (NCI-Molecular Analysis for Therapy Choice), a precision medicine trial open at more than 1,000 clinical sites. Codesigned by the ECOG-ACRIN Cancer Research Group and the NCI, and led by ECOG-ACRIN, NCI-MATCH is the most sweeping precision medicine trial in the United States. NCI-MATCH uses a customized tumor gene testing method to match patients with any solid tumor, along with lymphoma and myeloma, to multiple targeted treatments. Currently, there are 24 treatments offered, with plans to add about 10 more. Since NCI-MATCH was launched in August 2015, more than 2,500 patients have completed tumor gene testing out of the 6,000 patients intended to be screened. As of December 1, 2016, nearly 300 patients have entered treatment arms.
According to the definition used for the DART trial, rare cancers are those diseases with less than a 6 in 100,000 incidences per year. These include dozens of types, including cancers in nerves, glands, bones, and skin. But only certain patients will be eligible to enroll in DART. To join, patients must be registered to NCI-MATCH. If they don’t have a treatment option under NCI-MATCH, or if they didn’t respond to treatment on that trial, and their rare cancer is eligible, they can enroll......

cute and happy pics in tweetoff: #cuteanimaltweetoff


Invasive Cancer Incidence and Survival — United States, 2013 | MMWR

Invasive Cancer Incidence and Survival — United States, 2013 | MMWR

Centers for Disease Control and Prevention. CDC twenty four seven. Saving Lives, Protecting People


How useful is thrombocytosis in predicting an underlying cancer in primary care? a systematic review


Background. Although the association between raised platelet count (thrombocytosis) and cancer has been reported in primary and secondary care studies, UK GPs are unaware of it, and it is insufficiently evidenced for laboratories to identify and warn of it. This systematic review aimed to identify and collate evidence from studies that have investigated thrombocytosis as an early marker of cancer in primary care.
Methods. EMBASE (OvidSP), Medline (Ovid), Web of Science and The Cochrane Library were searched for relevant studies. Eligible studies had reported estimates of the association between thrombocytosis and cancer, in adults aged ≥40 in a primary care setting. Raw data from included studies were used to calculate positive predictive values and likelihood ratios (LRs) for cancer.
Results. Nine case–control studies were identified. Study quality was judged to be high. Included studies reported on the following cancer sites: colorectal, lung, ovary, bladder, kidney, pancreas, oesophago-gastric, uterus and breast. LRs indicated that thrombocytosis was a predictor of cancer in all sites except breast. In a consulting population, thrombocytosis is most highly predictive of lung and colorectal cancer.
Conclusions. These results suggest that patients with thrombocytosis in primary care have an increased risk of cancer, and that some, but not all, cancers have raised platelets as an early marker. This finding is expected to be of use in primary care, for GPs receiving blood test results unexpectedly showing high platelet counts. Further research is needed to identify the cancers that are most strongly associated with thrombocytosis.

Postoperative Chemotherapy in Young and Middle-Aged Patients With Colon Cancer

Blogger's Note: the abstract does not indicate if mutation analysis (eg. MLH1/MSH2) was included but given Lynch Syndrome (early age dx) it would have been interesting to note any differences, commentary indicates further research req'd but not specific mention of genetics

The JAMA Network (abstract)
Invited Commentary:  A Plea to Expand the Scope of Tumor Boards

Experts Forecast Cancer Research and Treatment Advances in 2017


11th International Symposium on Advanced Ovarian Cancer 2017

11th International Symposium on Advanced Ovarian Cancer

download scientific program (link) 


Wednesday, January 25, 2017

Cachexia: Symptoms, Treatment, and Outlook

Medical News

Researchers discover BRCA1 gene is key for blood forming stem cells (plus chemo side effects...)

Medical News Today

Researchers at from the Harold C. Simmons Comprehensive Cancer Center have found that the BRCA1 gene is required for the survival of blood forming stem cells, which could explain why patients with BRCA1 mutations do not have an elevated risk for leukemia. The stem cells die before they have an opportunity to transform into a blood cancer.
"One of the great mysteries in cancer research is why inherited mutations, such as those in BRCA1, cause cancer only in specific tissues such as the breast and ovaries, rather than in all tissues. Our data suggest a 'die or transform' hypothesis, which could explain this tissue specificity," said Dr. Theodora Ross, Professor of Internal Medicine and Director of the Cancer Genetics Program at UT Southwestern.
Additional data from this study suggest these patients may have a tougher time with the side effects of chemotherapy.
"Patients with certain BRCA1 mutations may be at a higher than expected risk for serious complications during chemotherapy treatment," said Dr. Ross, who holds the Jeanne Ann Plitt Professorship in Breast Cancer Research and the H. Ben and Isabelle T. Decherd Chair in Internal Medicine in Honor of Henry M. Winans, Sr., M.D. "If we confirm these clinical findings in upcoming studies, giving patients preventative antibiotics or growth factors may be necessary to lower this increased risk of treatment side effects.".......

 Article: Distinct Brca1 Mutations Differentially Reduce Hematopoietic Stem Cell Function, Victoria E. Mgbemena, Robert A.J. Signer, Ranjula Wijayatunge, Travis Laxson, Sean J. Morrison, Theodora S. Ross, Cell Reports, doi: 10.1016/j.celrep.2016.12.075, published 24 January 2017.

Comparative effectiveness of screening strategies for colorectal cancer

Blogger's Note: of interest due to the conflicts between the U.S. vs the Canadian recommendations in the general public; also of interest to Lynch Syndrome patients where annual/bi-annual colonoscopies are recommended but for Lynch Syndrome patients who might think to replace colonoscopies with alternative methods of testing


 This study compares the outcomes of various screening strategies on CRC outcomes.

Colonoscopy emerged as the most effective screening strategy with the highest life years gained and CRCs prevented and the lowest total costs...... Improved sensitivity or specificity of a screening test for CRC detection was not sufficient to close the outcomes gap compared with colonoscopy.

Expert Discusses Uncertainty Over Ideal IP Chemo Approach in Ovarian Cancer (GOG 252)

Monday, Jan 23, 2017
The much anticipated initial results of the Gynecologic Oncology Group (GOG) 252 trial failed to provide additional clarity for the use of intravenous (IV) versus intraperitoneal (IP) chemotherapy in patients with ovarian cancer, explains Franco M. Muggia, MD.

A Stanford Nutrition Professor on the 3 Food Myths Hurting Your Health


This week Christopher Gardner, a nutrition professor at Stanford University and a long-time vegetarian, debunks common misconceptions about healthy eating.

1. Carbohydrates. The anti-carb/low-carb craze has gone too far. 
2. Protein. Judging from the explosion of protein products -- a category that includes bars, smoothies, even protein water -- you’d think our national diet is deficient in this basic food component.
3. Fiber. What with all the attention being paid to carbohydrates and protein, it’s easy to forget about fiber. 

 The final word: Don’t buy into the industry-driven hype.

ASCO: (essay/book) What Cancer? - The Big CASINO

The ASCO Post

 I love to tell people that I have the best job in the world—I get to make a difference in the lives of heroes. I’ve learned about strength, faith, and resilience from my patients. I’ve learned about humility and putting others first. I’ve learned what love really means.