OVARIAN CANCER and US

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Saturday, December 03, 2016

top 10 most read articles (by you) this week/other stats: Ovarian Cancer and Us (blog)



 
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OA: Diagnosis of Lynch syndrome before colorectal resection: does it matter?



Diagnosis of Lynch syndrome before colorectal resection: does it matter?

Ovarian metastasis from uveal melanoma with MLH1/PMS2 protein loss in a patient with germline MLH1 mutated Lynch syndrome: consequence or coincidence?



 uveal tract
YOO-vee-ul trakt)
The middle layer of the wall of the eye. The uveal tract has 3 main parts: (1) the choroid (the tissue layer filled with blood vessels); (2) the ciliary body (the ring of muscle tissue that changes the size of the pupil and the shape of the lens); and (3) the iris (the colored part of the eye). Also called uvea.
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Ovarian metastasis from uveal melanoma with MLH1/PMS2 protein loss in a patient with germline MLH1 mutated Lynch syndrome: consequence or coincidence? 

Abstract
Currently, uveal melanoma is not considered within the Lynch syndrome tumor spectrum. However, there are studies suggesting a contribution of microsatellite instability in sporadic uveal melanoma tumorigenesis. We report a 45-year-old woman who was referred for genetic counseling due to a family history of Lynch syndrome caused by a MLH1 mutation. She originally underwent enucleation (removal) of the right eye secondary to a uveal spindle cell melanoma diagnosed at age 25. The tumor recurred 22 years later presenting as an ovarian metastasis and concurrently a microscopic endometrial endometrioid carcinoma, grade 1/3 was diagnosed. Subsequent studies highlighted that the uveal melanoma showed high microsatellite instability and loss of MLH1 and PMS2 protein expression, with no MLH1 promoter methylation or BRAF mutation. Additionally, a GNAQ mutation was found. We conclude that our patient’s uveal melanoma is most likely related to MLH1 germline mutation and thus Lynch syndrome related. To the best of our knowledge, this is the first report of uveal melanoma showing MLH1/PMS2 protein loss in the context of Lynch syndrome.

Fighting for the ‘right to try’: Terminally ill Canadians want legal right to access unproven treatments



National Post

New data on risk vs benefit for potent CAR-T cancer drugs | Reuters



Reuters

Ovarian Cancer : Articles



Ovarian Cancer : Articles (recent from RightRelevance.com)

Overspending Under Scrutiny | TVO.org re: Auditor General report video 23:05 min



Overspending Under Scrutiny | TVO.org
 
Air Date: 
Dec 02, 2016
Length: 
23:05
 
About this Video
The Auditor General of Ontario, Bonnie Lysyk, speaks with Steve Paikin about some of the key findings in her 2016 annual report. From overbilling by doctors and hospital wait times, to poor quality road repair and problems with contractors at Metrolinx, the report uncovers issues that cost taxpayers millions of dollars and also suggests solutions.

Prognostic significance of lymphadenectomy and prevalence of lymph node metastasis in clinically-apparent stage I endometrioid and mucinous ovarian carcinoma



Prognostic significance of lymphadenectomy and prevalence of lymph node metastasis in clinically-apparent stage I endometrioid and mucinous ovarian... 

 Abstract

OBJECTIVE:

The aim of the present study was to investigate the prevalence of lymph node (LN) metastasis in women with apparent stage I ovarian carcinoma of endometrioid or mucinous histology and to examine the prognostic significance of LN sampling/dissection (LND) on patient survival.

METHODS:

The National Cancer Institute's Surveillance, Epidemiology, and End Results database was accessed and a cohort of surgically-staged women, diagnosed between 1988 and 2013, with apparent stage I ovarian carcinoma of mucinous or endometrioid histology was selected. Information derived from the histopathology report was employed to determine whether LND was performed and the status of harvested LNs. Five-year cancer-specific survival (CSS) rate was calculated following generation of Kaplan-Meier curves. Comparisons were made using the log-rank test. Cox proportional hazard models were constructed to evaluate the effect of LND on survival.

RESULTS:

A total of 3354 and 2855 women with endometrioid and mucinous tumors who met the inclusion criteria were identified. LND was performed in 2307 (68.8%) and 1602 (56.1%) of them (p<0.001), respectively. The rate of histopathologically confirmed LN metastasis was 2.1% and 1.7%, respectively. By multivariate analysis LND was associated with superior cancer-specific mortality only for women with endometrioid carcinoma.

CONCLUSIONS:

Lymph node involvement in women with mucinous and endometrioid ovarian carcinoma grossly confined to the ovary is infrequent. LND is associated with a survival advantage for those with endometrioid carcinoma.

Metachronous Uterine Endometrioid Adenocarcinoma and Peritoneal Mesothelioma in Lynch Syndrome



Metachronous Uterine Endometrioid Adenocarcinoma and Peritoneal Mesothelioma in Lynch Syndrome

Abstract
 Lynch syndrome is a hereditary disease with germline mutation in a DNA mismatch repair gene, most often presenting with colorectal and/or endometrial carcinomas; however, the spectrum of Lynch syndrome–associated tumors is expanding. In this article, we report a case of a primary peritoneal epithelioid mesothelioma that developed in a Lynch syndrome patient 10 months after diagnosis of uterine endometrioid adenocarcinoma. To our knowledge, this is the first reported case of a Lynch syndrome patient with metachronous uterine endometrioid adenocarcinoma and primary peritoneal mesothelioma.

Incidence and survival rates of ovarian cancer in low-income women in Sudan



abstract: Incidence and survival rates of ovarian cancer in low-income women in Sudan


Abstract

Ovarian cancer is the second most common gynecological cancer worldwide. Little is known about the disease in Sudan. The objective of the present study was to evaluate the incidence rate, age and stage at diagnosis, and median survival time of patients presenting at the National Cancer Institute‑University of Gezira (NCI-UG), Sudan. Data were collected in a prospective study of women with ovarian cancer over a period of eleven years of follow‑up (between 2000 and 2011). Descriptive statistics were used to summarize the distribution of the demographics of the sample. The direct method was used to compute the age‑standardized rate (ASR) using data from the 1966 and 2000 World Standard Populations (WSPs). The Kaplan-Meier method was used to estimate survival functions and the median survival time. Log‑rank tests were used to statistically compare between the survival functions. There were steady increases in ovarian cancer incidence rates between 2000 and 2009, with a slight decline noted in 2010 and 2011. The patients' age range was 9‑90. The age‑specific incidence rate increased greatly in women aged 55 years or older. The majority of the patients had stage III or IV disease. The annual ASR using WSPs 1966 and 2000 as standard populations were 3.3 and 3.7 per 100,000 women, respectively. The median survival time was 31 months (95% confidence interval, 19‑43). The 5‑year cumulative survival rate was 38%. In Sudan, ovarian cancer affects postmenopausal women, akin to what is reported in the developed world with high incidence rates. Presenting with advanced stage disease is the predominant factor that results in a short survival time for women.

OA: Validation of the myBRCA HiRisk Hereditary Breast and Ovarian Cancer Test for Population Screening



Validation of the myBRCA HiRisk Hereditary Breast and Ovarian Cancer Test for Population Screening 

authors:  ¶Veritas Genetics, Danvers, MA 01923, §Massachusetts General Hospital, Boston, MA 02114 and & Harvard Medical School, Boston, MA 02115 

 Abstract
 
The myBRCA HiRisk test is a clinical est detecting mutations in 26 genes
associated with increased risk for breast and ovarian cancer. The test is based on next-generation sequencing and multiplex PCR del/dup detection and is performed in Veritas Genetics’ CLIA approved clinical laboratory. The test utilizes saliva or whole blood and was carefully validated on a diverse set of samples with variants representing both rare and relatively common pathogenic mutations. Validation
results are described.

 The analysis was performed blinded to exclude interpretation bias. All
positives counted were pathogenic, i.e., this analysis was not “padded” by including benign polymorphisms as true positives.

Genes tested in myBRCA HiRisk
 
ATM BARD1 BLM BRCA1
BRCA2 BRIP1 CDH1 CHEK2
EPCAM* FAM175A MEN1 MLH1
MRE11A MSH2 MSH6 MUTYH
NBN PALB2 PSM2 PTEN
RAD50 RAD51C RAD51D STK11
TP53 XRCC2
*del/dup analysis only

A Validation Study of Administrative Claims Data to Measure Ovarian Cancer Recurrence and Secondary Debulking Surgery



pdf

text version

A Validation Study of Administrative Claims Data to Measure Ovarian Cancer Recurrence and Secondary Debulking Surgery

(small study)  Abstract

Objective:

Administrative claims data offer an alternative to chart abstraction to assess ovarian cancer recurrence, treatment and outcomes. Such analyses have been hindered by lack of valid recurrence and treatment algorithms. In this study, we sought to develop claims-based algorithms to identify ovarian cancer recurrence and secondary debulking surgery, and to validate them against the gold-standard of chart abstraction.

Conclusions:

A recurrence algorithm based on treatment timing accurately identified ovarian cancer =recurrence. If validated in other populations, such an algorithm can provide a tool to compare effectiveness of recurrent ovarian cancer treatments.
                    ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

 Conclusions

Algorithms based on timing and utilization of select administrative billing codes for secondary treatment may be used to identify ovarian cancer recurrence and secondary debulking procedures. Applying these algorithms to existing sources of administrative
data can enable comparisons of treatment effects on recurrent ovarian cancer morbidity and mortality that can inform treatment decision-making in the
absence of clinical trial results.

70-Gene Signature in Early-Stage Breast Cancer — Comments (eg. QOL...)



70-Gene Signature in Early-Stage Breast Cancer — NEJM

The authors reply:

.....We agree that evaluating health-related quality of life is extremely important. However, patients in our study could potentially have been asked to sign four informed-consent documents, depending on their group assignment, and all the study patients had to comprehend the complexities of the trial, including information on genomic testing. We decided that the addition of quality-of-life questionnaires to the overall study would be too burdensome for the patients, a decision that was supported by patient advocates. At the time of the study, there existed no validated instrument to evaluate the psychological effects of genomic testing on patients, although we agree that such evaluation is important.

Friday, December 02, 2016

(Canada) Genetic discrimination bill headed back to Senate, Liberals deny it reopens possibility for government changes



Genetic discrimination bill headed back to Senate, Liberals deny it reopens possibility for government changes - The Hill Times - The Hill Times

https://www.hilltimes.com/2016/12/01/genetic-discrimination-bill-headed-back-senate-liberals-deny-reopens-possibility-government-changes/89756
While the substance of the bill was untouched, the House Justice Committee passed a coordinating amendment regarding the trans rights bill C-16 that could delay S-201’s passage.
PUBLISHED : Thursday, Dec. 1, 2016 3:12 PM
PARLIAMENT HILL—The bill that pit Liberal backbenchers against cabinet is headed back to the Senate, but not for the reason Justice Minister Jody Wilson-Raybould had hoped.
During Thursday’s clause-by-clause by the Justice and Human Rights Committee, the Senate public bill, S-201, Genetic Non-Discrimination Act passed as it was proposed, untouched, but on the suggestion of Liberal MP Colin Fraser (West Nova, N.S.), a coordinating amendment that will send the controversial, long-fought bill back to the Senate was also passed.
During the brief clause-by-clause on the bill, which was sponsored by Senate Liberal James Cowan, the 10 clauses of the bill as it was proposed passed the committee almost unanimously, but as the bill neared the end of receiving all the approvals needed to pass committee, Mr. Fraser, proposed adding a clause 11.
This clause, as proposed and passed, was aimed at protecting the intent of both Bill S-201 and Bill C-16, the government’s trans rights bill, because they propose to amend the same section of the Canadian Human Rights Act. The technical change added on to the bill makes it so that whichever bill passes second doesn’t override the wording of the first.

HESA - Development of a National Pharmacare Program (federal - Canada)



HESA - Development of a National Pharmacare Program

42nd Parliament, 1st Session
(December 3, 2015 - Present)

Development of a National Pharmacare Program

Last meeting: Thursday, December 1, 2016

Meetings

OA: (Comment) Precision medicine to precision care: managing multimorbidity - The Lancet



Precision medicine to precision care: managing multimorbidity - The Lancet

 Guidance for management of multimorbidity in clinical practice is insufficient.

(interview/video/text) Molecular Testing to Determine Gastric Cancer Treatment



 Molecular Testing to Determine Gastric Cancer Treatment

Panelists: Johanna C. Bendell, MD, Sarah Cannon Research Institute; Yelena Y. Janjigian, MD, Memorial Sloan Kettering Cancer Center; Manish Shah, MD, Weill Cornell Medical College; Ian Chau, MD, Royal Marsden Hospital
Published Online: Monday, Nov 28, 2016
Other hereditary syndromes, Lynch syndrome, is associated with gastric cancer. And also FAP is associated with gastric cancer, and that’s actually really quite interesting. A mutation in the APC gene, it affects beta-catenin signaling, and not only is it important in colon cancer, which we all know about, but it’s also important in gastric cancer. It gives you a 10-fold risk. There are things to be wary about, so I always ask my patients about their family history because it comes up not too infrequently.g to Determine Gastric Cancer Treatment

FDA Grants Priority Review to Pembrolizumab for MSI-H Cancer (including non-CRC)



FDA Grants Priority Review to Pembrolizumab for MSI-H Cancer

 In the 3-arm study that was the basis for the new designation, pembrolizumab was administered at 10 mg/kg every 2 weeks to patients with CRC who were MMR-deficient (n = 13) and MMR-proficient (n = 25). Additionally, a separate arm looked at pembrolizumab in patients with MMR-deficient non-CRC malignancies (n = 10). MMR and microsatellite instability testing was conducted using PCR and IHC, which are standard tests conducted for patients with CRC in order to detect Lynch syndrome.

 In the 48 patients analyzed from the study for the ASCO presentation, those with MMR-deficient CRC experienced a DCR of 92% compared with 16% in MMR-proficient tumors. After a median treatment duration of 5.9 months, no patients in the MMR-deficient group who responded had progressed. In patients with MMR-deficient non-CRC tumors, the ORR was 60% and the DCR was 70%.
OS and PFS were not reached in the MMR-deficient group versus a median PFS of 2.3 months (HR, 0.10; 95% CI, 0.03-0.37; P <.001) and an OS of 7.6 months in the MMR-proficient group (HR, 0.22; 95% CI, 0.05-1.00; P = .05)......

 The phase II study enrolled 3 patient cohorts. The first 2 cohorts were patients with CRC, while the third cohort included 21 patients with any solid gastrointestinal tumor that had mismatch repair deficiency.

...This Data from 17 patients with non-CRC GI cancers deficient in mismatch repair were available for analysis: 4 patients with ampullary cancer, 4 with pancreatic cancer, 3 with biliary cancer, 3 with small bowel cancer, and 3 with gastric cancer. Their median age was 60 years; 29% were female, 29% had an ECOG performance score of 0, and 100% had metastatic disease. The median number of prior regimens was 2.cohort was subsequently expanded by 50 patients.....Clinical benefit was observed across tumors with mismatch repair deficiency including cancers of the colon, stomach, duodenum, pancreas, ampulla, and bile ducts.

Novel Agent Moves Into Ovarian Cancer Combinations (fosbretabulin tromethamine)



Novel Agent Moves Into Ovarian Cancer Combinations


A recently launched clinical trial is exploring a new agent to treat patients with advanced, recurrent, platinum-resistant ovarian cancer. 
 
A clinical trial is looking to develop new therapeutic options for women with advanced, recurrent, platinum-resistant ovarian cancer by using a multipronged attack on the tumor vasculature network.

The novel agent fosbretabulin tromethamine is being combined with Avastin (bevacizumab) and physician’s choice of either paclitaxel or pegylated liposomal doxorubicin in the experimental arm of the phase 2/3 FOCUS study (NCT02641639). The regimen will be compared with Avastin plus chemotherapy, which is one option for this patient population.....

Dr Douglas A. Levine: Treatment Continues to Advance in Ovarian Cancer and Other Gynecologic Malignancies



Treatment Continues to Advance in Ovarian Cancer and Other Gynecologic Malignancies

 In an interview with CURE at the recent 2016 Chemotherapy Foundation Symposium, Levine, professor, Department of Obstetrics and Gynecology, director, Division of Gynecologic Oncology, NYU Langone Medical Center, discussed these agents and other advances toward precision medicine in the treatment of patients with gynecologic malignances.
 There has been major progress in treating gynecologic malignancies in recent years, especially for ovarian cancer, says Douglas A. Levine, M.D.
 Rucaparib was granted a priority review by the FDA in August 2016 for patients with BRCA-positive advanced ovarian cancer who have received two or more prior lines of chemotherapy. A final decision is expected by Feb. 23, 2017.

 And in November 2016, a new drug application to the FDA was completed for niraparib as a maintenance treatment for women with recurrent platinum-sensitive ovarian, fallopian tube or primary peritoneal cancer.....

Watson: A Glorified Search Engine?



Comment: Progress in PARP inhibitors beyond BRCA mutant recurrent ovarian cancer? - The Lancet Oncology



Progress in PARP inhibitors beyond BRCA mutant recurrent ovarian cancer? - The Lancet Oncology
 (not open access)
Up to half of newly diagnosed patients with high-grade serous ovarian cancer have a deficit in the homologous recombination system, which repairs double-strand breaks in DNA. Mutations in BRCA1 or BRCA2, which occur in roughly 20% of patients (16% germline and 4% somatic), are the most common cause of homologous recombination deficiency.1 Patients with BRCA mutations have longer overall survival than do patients without such mutations, and their tumours are extremely sensitive to platinum-based chemotherapy and poly (ADP-ribose) polymerase (PARP) inhibitors.

References 


References

  1. Nielsen, FC, van Overeem Hansen, T, and Sørensen, CS. Hereditary breast and ovarian cancer: new genes in confined pathways. Nat Rev Cancer. 2016; 16: 599–612
  2. Konstantinopoulos, PA, Ceccaldi, R, Shapiro, GI, and D'Andrea, AD. Homologous recombination deficiency: exploiting the fundamental vulnerability of ovarian cancer. Cancer Discov. 2015; 5: 1137–1154
  3. Ledermann, J, Harter, P, Gourley, C et al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol. 2014; 15: 852–861
  4. Kaufman, B, Shapira-Frommer, R, Schmutzler, RK et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015; 33: 244–250
  5. Gelmon, KA, Tischkowitz, M, Mackay, H et al. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncol. 2011; 12: 852–861
  6. Abkevich, V, Timms, KM, Hennessy, BT et al. Patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer. Br J Cancer. 2012; 107: 1776–1782
  7. Watkins, JA, Irshad, S, Grigoriadis, A, and Tutt, AN. Genomic scars as biomarkers of homologous recombination deficiency and drug response in breast and ovarian cancers. Breast Cancer Res. 2014; 16: 211
  8. Swisher, EM, Lin, KK, Oza, AM et al. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncology. 2016; (published online Nov 28.)http://dx.doi.org/10.1016/S1470-2045(16)30559-9.
  9. Coleman, RL, Swisher, EM, and Oza, AM. Refinement of prespecified cutoff for genomic loss of heterozygosity in ARIEL2 part 1: a phase II study of rucaparib in patients (pts) with high grade ovarian carcinoma. Proc Am Soc Clin Oncol. 2016; 34 (abstr 5540.)
  10. Mirza, MR, Monk, BJ, Herrstedt, J et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med. 2016; (published online Oct 7.)

Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial



Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial - The Lancet Oncology

  This trial is registered with ClinicalTrials.gov, number NCT01891344. Enrolment into ARIEL2 Part 1 is complete, although an extension (Part 2) is ongoing.

 ARIEL2 is an international, multicentre, two-part, phase 2, open-label study done at 49 hospitals and cancer centres in Australia, Canada, France, Spain, the UK, and the USA. In ARIEL2 Part 1, patients with recurrent, platinum-sensitive, high-grade ovarian carcinoma.....

 Interpretation
In patients with BRCA mutant or BRCA wild-type and LOH high platinum-sensitive ovarian carcinomas treated with rucaparib, progression-free survival was longer than in patients with BRCA wild-type LOH low carcinomas. Our results suggest that assessment of tumour LOH can be used to identify patients with BRCA wild-type platinum-sensitive ovarian cancers who might benefit from rucaparib. These results extend the potential usefulness of PARP inhibitors in the treatment setting beyond BRCA mutant tumours.

Rucaparib Prolongs PFS in Ovarian Cancer



Rucaparib Prolongs PFS in Ovarian Cancer - Cancer Therapy Advisor

  The findings suggest that evaluation of tumor LOH can help to identify patients with BRCA wild-type platinum-sensitive ovarian carcinomas who might benefit from treatment with rucaparib.
Reference
  1. Swisher EM, Lin KK, Oza AM, et al. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016 Nov 28. doi: 10.1016/S1470-2045(16)30559-9 [Epub ahead of print]

Reducing research waste – messages from the Cochrane community



Reducing research waste – messages from the Cochrane community | Cochrane Community


Key messages from the survey and the Special Session include:
  • Support priority setting processes for systematic reviews. All Cochrane Review Groups are already encouraged to engage in a formal prioritization process, and many Cochrane Review Groups are already defining their priorities and examples are being documented. However, the processes followed to define the priorities vary, and it also remains a challenge to include priorities of disadvantaged groups and low and middle income countries. Not surprisingly, about 60% of survey respondents indicated Cochrane could do more in priority setting, for example by being more inclusive and by developing a clearer and more consistent process.
  • Advocate for systematic reviews with funding organizations: 86% of respondents to the survey felt that Cochrane could do more in working with research funders in advocating systematic reviews be conducted prior to funding new research.
  • Speed up the ‘empty review’ process: 62% of survey respondents indicated that ‘empty reviews’ (reviews that have no studies eligible for inclusion or only included a single small RCT) are very to extremely important. “Empty reviews are important but they ought to take weeks not months, at least once the search is complete. As soon as you see the review is empty, getting that out should be very, very quick.” In response to this concern, Cochrane will change the focus of ‘empty reviews’ from guiding clinical practices to identifying research gaps and stimulating further research in relevant areas. A pilot to change the editorial process for empty reviews will take place in 2017.
  • Work with partners to strengthen reporting of research: 60% of survey respondents felt that Cochrane should do more in ensuring better reporting of research and research results, among other in clinical trial registries, especially through working with strategic partners such as AllTrials and WHO ICTRP.
  • Automate the review process: The production of more rapid reviews is important and automation tools are a means to do this. Project Transform is an important step in this direction, but will need continued contribution from the Cochrane community and beyond to succeed.

OA: Cancer-associated thrombosis and palliative care: an interview with Simon Noble



Cancer-associated thrombosis and palliative care: an interview with Simon Noble, Future Oncology, Future Medicine

 Q CAT is a condition that is not normally discussed, despite it being one of the leading causes of death in cancer patients. Can you tell our readers more about the condition & the risk factors involved?
 Another thing that is very important to note is that 52% of people that get CAT will do so in the first 3 months of diagnosis of cancer. So you have people who are still reeling from their diagnosis of a life-threatening condition and then usually within 3 months of that, usually as they have just started their treatment for it, they will then have another life-threatening condition that is either a deep vein thrombosis or a pulmonary embolus; so the psychological impact of that cannot be underestimated.

...Interestingly, we have done some other research in noncancer patients, which shows that patients who have experienced a clot will develop ongoing anxiety and distress, and proportion of them will develop post-traumatic stress disorder. One of the reasons that triggers post-traumatic stress disorder is an unexpected threat to life and then living with the unknowing of whether that threat is likely to return so it is that uncertainty which causes a lot of the distress....


Q Can you tell our readers about your current research & other ongoing studies?

Previous sectionNext section
First of all I am continuing the PELICAN study. We have analyzed data from Spain, which we are writing up at the moment and we are also analyzing data from Canada. We have still got data from France coming in and we have opened recently in New Zealand. We have also got other countries that are opening such as Manila, Singapore and also The Netherlands. We have now got quite a few countries still going so that will be very interesting.....
 (Patient Experience of LIving with CANcer associated thrombosis)

Thursday, December 01, 2016

OA: Which BRCA genetic testing programs are ready for implementation in health care? A systematic review of economic evaluations



Which BRCA genetic testing programs are ready for implementation in health care? A systematic review of economic evaluations : Genetics in Medicine

 The main challenge in conducting a systematic review of economic evaluations derives from their high degree of heterogeneity, meaning that results cannot be pooled across studies by meta-analysis or other quantitative synthesis methods.12,13 Consequently, the majority of such reviews have presented the results obtained in a narrative format.11
   Our survey of the literature found only nine full economic evaluations of BRCA genetic testing. Most of these were of acceptable quality, although some methodological limitations should be mentioned. For example, the included costs were frequently inadequate. Thus, although the societal perspective is the most appropriate for the analysis of health-care programs and five economic evaluations adopted this perspective, none of the authors included social costs.

In conclusion, the results of this systematic review indicate that, although BRCA1/2 population-based screening is currently an inefficient use of health-care resources, population-based screening of the AJ (Ashkenazi Jewish) community appears to be a good value for the money. Furthermore, it is highly likely that FH-based (family-history) screening will prove cost-effective, although further economic evaluations that include the costs of identifying high-risk women are needed to fully justify this conclusion. This point is crucial because counseling strategies to detect at-risk individuals could involve primary-care physicians, and currently physicians seem to be not yet adequately prepared about hereditary breast cancer and BRCA1/2 testing.47,48 Finally, in contrast to genetic testing for hereditary colorectal cancer (i.e., Lynch syndrome),49,50,51 there is no evidence for the cost-effectiveness of screening for BRCA1/2 of newly diagnosed cases of breast and ovarian cancers, followed by cascade testing of relatives. However, cancer-based genetic screening programs for BRCA1/2 that includes tools for identifying women at higher risk for inherited forms are very promising in terms of cost-effectiveness. On the contrary, more high-quality studies are needed to prove the cost-effectiveness of BRCA genetic testing as an instrument of secondary prevention in affected women with predisposing gene mutation.

In any case, the price of BRCA1/2 testing is of paramount importance in determining the cost-effectiveness of BRCA1/2 testing programs.44 If the cost of testing falls significantly, then all BRCA1/2 testing strategies analyzed in this review—perhaps including population-based screening—are likely to become highly cost-effective interventions.

Excess weight as a risk factor common to many cancer sites: words of caution when interpreting meta-analytic evidence



Excess weight as a risk factor common to many cancer sites: words of caution when interpreting meta-analytic evidence | Cancer Epidemiology, Biomarkers & Prevention

Abstract
 For over a decade, excess body weight, commonly categorized as overweight (body mass index, BMI: 25.0 to 29.9 kg/m2) and obesity (BMI: ≥ 30 kg/m2) has been an established incidence risk factor for several adult cancers (1). For 2012, the burden of disease attributed to elevated BMI was estimated as nearly half-million new cancers worldwide, making this the third highest ranked cancer risk factor globally after smoking and infections (ranked second in most western populations) and an important public health problem (2, 3). In recent years, scientific evidence on BMI-cancer associations has continued to accumulate and reveal positive associations for even more and more cancer sites. Among the most comprehensive and systematic evaluations undertaken on these associations have been through the World Cancer Research Fund (WCRF) continuous update project, which now links excess weight or body fatness to 11 cancers (4).

In 2016, an expert working group of 21 scientists from eight countries, gathered under the auspices of the International Agency for Research on Cancer (IARC), to evaluate the preventive effects of avoidance of excess body fatness on cancer risk. This group extended the list of obesity-related cancers, for which sufficient evidence exists, to thirteen as follows: cancers of the colon and rectum, esophagus (adenocarcinoma), kidney (renal cell), breast (post-menopausal), endometrium, gastric cardia, liver, gallbladder, pancreas, ovary, thyroid, multiple myeloma and meningioma. Considering that excess body adiposity is related to a vast array of metabolic and physiological dysfunctions, underlying biological mechanisms have been identified explaining many of these associations.

Primary Resistance to PD-1 Blockade Mediated by JAK½ Mutations



Primary Resistance to PD-1 Blockade Mediated by JAK½ Mutations |abstract

 Loss of function mutations in JAK½ can lead to acquired resistance to anti-programmed death protein 1 (PD-1) therapy. We reasoned they may also be involved in primary resistance to anti-PD-1 therapy. JAK½ inactivating mutations were noted in tumor biopsies of 1 of 23 patients with melanoma and in 1 of 16 patients with mismatch repair deficient colon cancer treated with PD-1 blockade. Both cases had a high mutational load but did not respond to anti-PD-1 therapy. Two out of 48 human melanoma cell lines had JAK½ mutations, which led to lack of PD-L1 expression upon interferon gamma exposure mediated by inability to signal through the interferon gamma receptor pathway. JAK½ loss-of-function alterations in TCGA confer adverse outcomes in patients. We propose that JAK½ loss-of-function mutations are a genetic mechanism of lack of reactive PD-L1 expression and response to interferon gamma, leading to primary resistance to PD-1 blockade therapy.

(aka. the reality of some lawsuit/settlements) Jarvis: $1,500 for a lifetime of worry and fear (media/diluted chemo/lawsuits)



Jarvis: $1,500 for a lifetime of worry and fear

Should research volunteers get to see their medical tests?



Should research volunteers get to see their medical tests?

 

Medscape Ethics Report 2016: Money, Romance, and Patients



Medscape Ethics Report 2016: Money, Romance, and Patients