Genomics in upper tract urothelial carcinoma (UTUC) - paywalled

abstract
 2016 Aug 31
 

PURPOSE OF REVIEW:

Upper tract urothelial carcinoma (UTUC) is a relatively rare and poorly investigated disease. The objective of this review was to discuss recent advances in genomics and their implication regarding prognosis and treatment.

RECENT FINDINGS:

UTUC were compared with urothelial carcinoma of the bladder (UCB) at genomic and transcriptomic levels. Molecular studies focused on identifying new prognostic biomarkers that were often initially described in UCB and extrapolated to UTUC. Some of them could be interesting to improve the management of UTUC.

SUMMARY:

Recent studies improved our understanding of UTUC as a distinct entity compared with UCB. Although UTUC shares many of the same genomic alterations with UCB, some key differences have been identified as oncogenic drivers of these cancers. This better comprehension of genomics could lead to new prognostic markers that may refine UTUC treatment.

ESGO Quality Indicators for Advanced Ovarian Cancer Surgery

abstract
  International Journal of Gynecological Cancer:

September 2016 - Volume 26 - Issue 7 - p 1354–1363

Cooperative Groups

Objectives: The surgical management of advanced ovarian cancer involves complex surgery. Implementation of a quality management program has a major impact on survival. The goal of this work was to develop a list of quality indicators (QIs) for advanced ovarian cancer surgery that can be used to audit and improve the clinical practice. This task has been carried out under the auspices of the European Society of Gynaecologic Oncology (ESGO).

Methods: Quality indicators were based on scientific evidence and/or expert consensus. A 4-step evaluation process included a systematic literature search for the identification of potential QIs and the documentation of scientific evidence, physical meetings of an ad hoc multidisciplinarity International Development Group, an internal validation of the targets and scoring system, and an external review process involving physicians and patients.

Results: Ten structural, process, or outcome indicators were selected. Quality indicators 1 to 3 are related to achievement of complete cytoreduction, caseload in the center, training, and experience of the surgeon. Quality indicators 4 to 6 are related to the overall management, including active participation to clinical research, decision-making process within a structured multidisciplinary team, and preoperative workup. Quality indicator 7 addresses the high value of adequate perioperative management. Quality indicators 8 to 10 highlight the need of recording pertinent information relevant to improvement of quality. An ESGO-approved template for the operative report has been designed. Quality indicators were described using a structured format specifying what the indicator is measuring, measurability specifications, and targets. Each QI was associated with a score, and an assessment form was built.

Conclusions: The ESGO quality criteria can be used for self-assessment, for institutional or governmental quality assurance programs, and for the certification of centers. Quality indicators and corresponding targets give practitioners and health administrators a quantitative basis for improving care and organizational processes in the surgical management of advanced ovarian cancer.

Leveraging premalignant biology for immune-based cancer prevention (eg. Lynch/inherited syndromes...)

abstract
 Dana–Farber Cancer Institute
Prevention is an essential component of cancer eradication. Next-generation sequencing of cancer genomes and epigenomes has defined large numbers of driver mutations and molecular subgroups, leading to therapeutic advances. By comparison, there is a relative paucity of such knowledge in premalignant neoplasia, which inherently limits the potential to develop precision prevention strategies. Studies on the interplay between germ-line and somatic events have elucidated genetic processes underlying premalignant progression and preventive targets. Emerging data hint at the immune system’s ability to intercept premalignancy and prevent cancer. Genetically engineered mouse models have identified mechanisms by which genetic drivers and other somatic alterations recruit inflammatory cells and induce changes in normal cells to create and interact with the premalignant tumor microenvironment to promote oncogenesis and immune evasion. These studies are currently limited to only a few lesion types and patients. In this Perspective, we advocate a large-scale collaborative effort to systematically map the biology of premalignancy and the surrounding cellular response. By bringing together scientists from diverse disciplines (e.g., biochemistry, omics, and computational biology; microbiology, immunology, and medical genetics; engineering, imaging, and synthetic chemistry; and implementation science), we can drive a concerted effort focused on cancer vaccines to reprogram the immune response to prevent, detect, and reject premalignancy. Lynch syndrome, clonal hematopoiesis, and cervical intraepithelial neoplasia which also serve as models for inherited syndromes, blood, and viral premalignancies, are ideal scenarios in which to launch this initiative. 

Factors associated with cancer worries in individuals participating in annual pancreatic cancer surveillance (at risk)

open access

Surprisingly, a factor not associated with high cancer worries, was a personal history of cancer.

Obesity: The fat advantage (the obesity paradox)

Nature : Nature Research

“Genetic Predisposition in Gynecologic Cancers” (Lynch & ovarian??) paywalled

abstract - Seminars in Oncology

Dept. of Gynecologic Oncology and Reproductive Medicine, MD Anderson Cancer Center, 1155 Pressler, Unit 1362, Houston, TX 77030

 This review article discusses the diagnosis and management of hereditary ovarian cancer and hereditary uterine cancer. The key recommendations highlighted are: All women with high grade non-mucinous epithelial ovarian cancer should be offered at least BRCA1 and BRCA2 genetic testing. The care of women with BRCA-associated ovarian cancer should be tailored to their mutation status. Risk reducing bilateral salpingo-oophorectomy is recommended for women with BRCA1/2 mutations. Women with endometrial cancer should be assessed for the possibility of Lynch syndrome. Individuals with Lynch syndrome should undergo screening colonoscopy every 1-2 years. Lynch syndrome causes a high risk of endometrial cancer, and women with Lynch syndrome should consult with a gynecologic specialist to formulate a plan for managing this risk.

Unfinished business: women's health inequality in the USA - The Lancet

The Lancet

US Election 2016 - the Lancet

US Election 2016

 Health care has not so far been a dominant issue in the forthcoming US presidential election, but is certain to become a key topic in the build-up to election day on Nov 8, 2016. The Lancet presents its own health platform ahead of the election, and will be highlighting the key health challenges facing the US up to election day and beyond.

In silico, in vitro and case-control analyses as an effective combination for analyzing BRCA1 and BRCA2 unclassified variants in a population-based (Spain) sample

 in silico

adjective & adverb

1. (of scientific experiments or research) conducted or produced by means of computer modeling or computer simulation.

   "in silico analysis of the human genome"

                            ~~~~~~~~~~~~~~~~~~~~~~~

abstract

 Ascertaining the clinical consequences of BRCA1 and BRCA2 variants of uncertain significance (VUS) is currently indispensable for providing effective genetic counseling and preventive actions for families with hereditary breast and ovarian cancer (HBOC). To this end, we conducted a combination of in silico prediction and cDNA splicing analyses of 13 BRCA1 and 10 BRCA2 VUS identified in our cohort as well as a case-control analysis in a population-based sample of 10 recurrent VUS. We observed consistent results between the in silico predictions and sequencing analyses for all analyzed VUS. An abnormal cDNA pattern was observed for variants c.212+1G>A and c.5278-1G>A in BRCA1 and c.516+2T>A and c.8168A>G in BRCA2 according to in silico splicing prediction.. A case-control study of VUS confirmed the polymorphisms of the c.67+62A>G, c.7008-62A>G and c.8851G>A BRCA2 variants previously published. c.4068G>A in the BRCA2 gene can also be considered a polymorphism due to its occurrence at a frequency greater than 1% in our population.
Our study shows that employing population-based analysis and a combination of several in silico methods yields highly accurate information, resulting in a reliable tool for selecting variants for cDNA sequencing analysis in routine cancer genetic counseling units.

Tesaro Receives FDA Fast Track Designation for Niraparib and Initiates Rolling NDA Submission

medical news

"The initiation of this rolling NDA submission is a significant milestone for Tesaro, and we are committed to working collaboratively with the FDA to advance the review of the niraparib application," said Mary Lynne Hedley, Ph.D., President and COO of Tesaro. "We look forward to presentation of data from the Phase 3 NOVA trial of niraparib in a Presidential Symposium session at the European Society for Medical Oncology (ESMO) congress on October 8."
NOVA is a double-blind, placebo-controlled, international Phase 3 trial of niraparib that enrolled more than 500 patients with recurrent ovarian cancer who were in a response to their most recent platinum-based chemotherapy.

Register - event: Sept 22nd 6pm EDT: Saving Lives with Ovarian Cancer Prevention - An Update from the Ovarian Cancer Dream Team

 
Saving Lives with Ovarian Cancer Prevention - An Update from the Ovarian Cancer Dream Team

Registration is required to join this event. If you have not registered, please do so now.

Event status:

	Not started (Register)
Date and time:	Thursday, September 22, 2016 6:00 pm Eastern Daylight Time (New York, GMT-04:00) Change time zone
Duration:	1 hour
Description:	Join OCRFA and Dr. Elizabeth Swisher to hear about the exciting progress being made by the Stand Up to Cancer Ovarian Cancer Dream Team! The SU2C Ovarian Cancer Dream Team, funded by OCRFA and NOCC, got to work on year ago. Dr. Swisher, a gynecologic oncologist at the University of Washington and co-leader of the Dream Team, will update us on the progress the Team is making on this important and ambitious research project. About Dr. Elizabeth Swisher Elizabeth Swisher, MD, graduated cum laude from Yale University and received her medical degree from the University of California at San Diego. She completed her residency in obstetrics and gynecology at the University of Washington and a fellowship in gynecologic oncology at Washington University, St Louis. She joined the faculty at the University of Washington in 1999 where she is currently a Professor in the Department of Obstetrics and Gynecology, Division of Gynecologic Oncology and an adjunct Professor in the Department of Medicine, Division of Medical Genetics. Both her clinical and laboratory work focus on cancer genetics. She is medical director of the Breast and Ovarian Cancer Prevention Program at the Seattle Cancer Care Alliance. Her research has been funded by the NIH, the Department of Defense, the Ovarian Cancer Research Fund, and other cancer foundations. Dr. Swisher’s research has primarily focused on understanding the early events of ovarian carcinogenesis and on the development of novel biomarkers of disease and prognosis, with an emphasis on the role of the BRCA-Fanconi anemia pathway. She has been exploring how a better understanding of this pathway can lead to more effective therapies and prevention of ovarian cancers. She is principal investigator on several PARP inhibitor therapeutic trials and leads the translational research for numerous other clinical trials. Her overall goal is to reduce the burden of ovarian cancer by combining broader identification of inherited risk with effective prevention.

 

Patients Canada event (Toronto): Putting the Patient in Patient-centred Care Sept. 21st

Patients Canada
 Event details
Wednesday, Sept 21, 2016
6:30 - 8:00PM EST

 Townhall with Ontario's Patient Ombudsman, Christine Elliott

 

Patients Canada invites you to the inaugural townhall of Ontario's newly-appointed Patient Ombudsman, Christine Elliott.

 

This interactive and exciting event will be moderated by well-known Canadian journalist Steve Paikin, host of TVO's The Agenda with Steve Paikin. This is your opportunity to connect with the Patient Ombudsman and hear what she can do for patients.
 

Join the conversation via livestream...

patientscanada.ca/patientslivestream

 

*Please note that this event will be video recorded and photographed.

Finding Relief for Suffering From Cancer Pain - video/interview 7:08 min

Finding Relief for Suffering From Cancer Pain

 Description: How do I manage my cancer pain? Patient Power Founder and Host, Andrew Schorr, interviews MD Anderson Cancer Center's pain management specialist, Dr. David Hui. Dr. Hui has devoted his career to helping cancer patients find relief from their pain. Listen as he describes various types of pain and explains how to best manage your care and seek relief.

Correspondence: Flawed external validation study of the ADNEX model to diagnose ovarian cancer

open access

14 September 2016
 

Dear Editor,

 

External validation studies of prediction models are of utmost importance in order to assess the performance of a prediction model in different locations (Altman et al., 2009). We therefore read with interest the recent external validation study of the ADNEX model (Szubert et al., 2016)......

Ref:  Szubert et al., 2016

1. • S. Szubert, A. Wojtowicz, R. Moszynski, P. Zywica, K. Dyczkowski, A. Stachowiak, et al.
   • External validation of the IOTA ADNEX model performed by two independent gynecologic centers
   • Gynecol. Oncol. (2016)

   • Highlights (abstract)

      

     •

     We performed external validation of IOTA ADNEX model in two European centers.

     •

     The study confirms high discrimination accuracy of the ADNEX model.

     •

     The prediction of specific tumor type had moderate performance.

     •

     The results were comparable to original IOTA report and similar between two centers.

References

1. • Altman et al., 2009
   • D.G. Altman, Y. Vergouwe, P. Royston, K.G. Moons
   • Prognosis and prognostic research: validating a prognostic model
   • BMJ, 338 (2009), p. b605
   • CrossRef
     |
     View Record in Scopus
      | 
     Citing articles (5)
2. • Collins et al., 2016
   • G.S. Collins, E.O. Ogundimu, D.G. Altman
   • Sample size considerations for the external validation of a multivariable prognostic model: a resampling study
   • Stat. Med., 35 (2016), pp. 214–226
   • CrossRef
     |
     View Record in Scopus
      | 
     Citing articles (7)

Post-diagnosis Weight Change and Survival Following a Diagnosis of Early Stage Breast Cancer

abstract:

Post-diagnosis Weight Change and Survival Following a Diagnosis of Early Stage Breast Cancer | Cancer Epidemiology, Biomarkers & Prevention
 

 Impact: Weight loss and gain are equally common after breast cancer, and weight loss is a consistent marker of mortality risk.

Background: Achieving healthy weight is recommended for all breast cancer survivors. Previous research on post-diagnosis weight change and mortality had conflicting results.

changes to blog search - Ovarian Cancer and Us

(Note: blogger is Google based) By September 29, 2016, the Search Box gadget on this blog will only present search results from this blog. Search results from pages linked in your posts, from the Web or from the Blog List and Link List gadgets will not be presented anymore.

Editorial: How to Select Neoadjuvant Chemotherapy or Primary Debulking Surgery in Patients With Stage IIIC or IV Ovarian Carcinoma

open access
September 19. 2016

 Conclusion Use of NACT increased significantly between 2003 and 2012. In this observational study, PCS was associated with increased survival in stage IIIC, but not stage IV disease. Future studies should prospectively consider the efficacy of NACT by extent of residual disease in unselected patients.

Footnotes

• See accompanying article doi:10.1200/JCO.2016.68.1239

  Use and Effectiveness of Neoadjuvant Chemotherapy for Treatment of Ovarian Cancer September 6, 2016

REFERENCES

1. 1.↵
   1. Vergote I,
   2. De Wever I,
   3. Tjalma W,
   4. et al.

   (1998) Neoadjuvant chemotherapy or primary debulking surgery in advanced ovarian carcinoma: A retrospective analysis of 285 patients. Gynecol Oncol 71:431–436.

   CrossRefMedlineGoogle Scholar
2. 2.↵
   1. Vergote I,
   2. Tropé CG,
   3. Amant F,
   4. et al.

   (2010) Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med 363:943–953.

   CrossRefMedlineGoogle Scholar
3. 3.↵
   1. Kehoe S,
   2. Hook J,
   3. Nankivell M,
   4. et al.

   (2015) Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): An open-label, randomised, controlled, non-inferiority trial. Lancet 386:249–257.

   CrossRefMedlineGoogle Scholar
4. 4.↵
   1. Meyer LA,
   2. Cronin AM,
   3. Sun CC,
   4. et al.

   Use and effectiveness of neoadjuvant chemotherapy for treatment of ovarian cancer. J Clin Oncol, doi:10.1200/JCO.2016.68.1239.

Extended carboplatin infusion does not reduce frequency of hypersensitivity reaction at initiation of retreatment in patients with recurrent platinum-sensitive ovarian cancer

no abstract
September 15, 2016

'Mystery Shoppers' Call About Palliative Care, Get Mixed Bag

Medscape (U.S.)

Overall Survival in Patients With Platinum-Sensitive Recurrent Serous Ovarian Cancer Receiving Olaparib Maintenance Monotherapy

PracticeUpdate
  

TAKE-HOME MESSAGE

• This study included 265 patients with BRCA-mutated platinum-sensitive recurrent serous ovarian cancer who were randomized to receive olaparib or placebo. A survival advantage was observed in all patients who received olaparib compared with placebo. A total of 22% of patients receiving olaparib and 9% of patients receiving placebo reported serious adverse events.
  
• These data support the tolerability and long-term benefit of maintenance olaparib in this patient population.

Additional Info

• Article Citation

The Lancet Oncology

Overall Survival in Patients With Platinum-Sensitive Recurrent Serous Ovarian Cancer Receiving Olaparib Maintenance Monotherapy: An Updated Analysis From a Randomised, Placebo-Controlled, Double-Blind, Phase 2 Trial

Lancet Oncol 2016 Sep 08;[EPub Ahead of Print], JA Ledermann, P Harter, C Gourley, M Friedlander, I Vergote, G Rustin, C Scott, W Meier, R Shapira-Frommer, T Safra, D Matei, A Fielding, S Spencer, P Rowe, E Lowe, D Hodgson, MA Sovak, U Matulonis

Olaparib Maintenance Fails to Significantly Prolong Survival in Ovarian Cancer

medical news
 September 12, 2016

What’s New in Genetic Testing for Cancer Susceptibility? open access

Cancer Network - open access - see Tables for further information

Featured Article

What’s New in Genetic Testing for Cancer Susceptibility?

The dilemma for clinicians is how best to understand and manage this rapidly growing body of information to improve patient care. With millions of genetic variants of potential clinical significance and thousands of genes associated with rare but well-established genetic conditions, the complexities of genetic data management clearly will require improved computerized clinical decision support tools, as opposed to continued reliance on traditional rote, memory-based medicine.