Reservations About Salpingo-oophorectomy Without Hysterectomy

partial view: The JAMA Network

Reservations About Risk-Reducing Salpingo-oophorectomy Without Hysterectomy in Women With BRCA Mutations

Steven A. Narod, MD¹

Author Affiliations

JAMA Oncol. Published online November 10, 2016. doi:10.1001/jamaoncol.2016.3952

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Articles

• Original Investigation
  Uterine Cancer After Risk-Reducing Salpingo-oophorectomy
  
  
• Comment & Response
  Reservations About Salpingo-oophorectomy Without Hysterectomy
  
  

To The Editor In the study by Shu et al,¹ the investigators conducted a multicenter prospective cohort study of 1083 women with a BRCA1 or BRCA2 mutation at 9 academic medical centers in the United States or the United Kingdom. They observed 8 incident uterine cancers, compared with 4.3 expected. In my opinion this is erroneously described as a “prospective cohort study” because all of the incident cancers had been diagnosed at the time when the cohort was designed and assembled. The patients were ascertained from 1995 on, but the cohort was assembled in 2014 by inviting potential participants around the world to join the study group after the all cancers had already been diagnosed. It is my understanding that for a cohort study to be valid, the cohort should be assembled and followed forward in time (prospectively) or constructed through a formal and rigid and evaluable process of an existing data set (historical). The study by Shu et al¹ does not qualify in either case, and at Womens’ College Hospital we will not be relying on the results of this study on its own to advise our patients on the benefits of a hysterectomy in addition to salpingo-oophorectomy.

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AICR Research Conference November 14-16 (program/details)

American Institute for Cancer Research (AICR)

The 2016 AICR Research Conference will feature an exciting program which will explore current topic in nutrition, physical activity, obesity and cancer. Join fellow scientists, researchers, health professionals and dietitians to hear about the latest research in these areas:

• Energy Balance, Obesity and Physical Activity – Emerging Concepts and Strategies for Intervention
• Dietary Supplements and Cancer Risk: What We Have Learned
• Dietary Modulation of the Microbiome and Cancer Risk
• Nutrition After Cancer Diagnosis
• Mechanisms and Biomarkers in the –omics Era   
• Social, Cultural and Economic Barriers to Cancer Prevention and Control
• Food, Nutrition and Cancer Immunology: Etiology, Therapy and Survivorship
• Dietary Patterns: Clarifying the Relationship between Diet and Cancer
• Diet, Nutrition, Physical Activity and Cancer: Science and Translation for the Next 25 Years

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IBM Watson, Broad Institute team up on $50M cancer drug resistance project

Biotech
 Nov 10, 2016
 IBM Watson is kicking off another oncology partnership, this time with the Broad Institute of MIT and Harvard University. The $50 million tie-up will have the pair examining genome data from 10,000 drug-resistant tumors and cell line studies, with the goal of understanding the drivers behind cancer drug resistance and developing new treatments.....

 Unlike earlier studies, this project will have a broad focus rather than pinpoint a specific cancer,

BMC Nutrition - open access journal

Home page

 Aims and scope

BMC Nutrition is an open access, peer-reviewed journal that considers articles on all aspects of nutritional sciences, including public health nutrition and global interventions, nutritional epidemiology, the biological underpinnings of nutrition in the body, clinical nutrition, health and nutrition throughout the lifecourse, and dietary supplementation for improvement in health and performance. The journal also welcomes papers on developments in nutritional research tools and novel technologies.

Vision for a Great OMA - shawn whatley md (resignation from Ontario Medical Association board + comments)

blog

 I resigned from the Board of the Ontario Medical Association yesterday. I believe that the OMA can do better.

author of:

No More Lethal Waits: 10 Steps to Transform Canada's Emergency Departments Paperback – Jan 28 2016

 

Ovarian Cancer Recurrence: Discussion With an Expert (Scott Richard, M.D.)

curetoday

CURE spoke with Scott Richard, M.D., associate professor at the Sidney Kimmel Medical College at Thomas Jefferson University about ovarian cancer recurrence, and what more needs to be done in the field. - See more at: http://www.curetoday.com/articles/ovarian-cancer-recurrence-discussion-with-an-expert?eKey=c2FuZGlwbkBzeW1wYXRpY28uY2E=#sthash.rATXeI8M.dpuf

CURE spoke with Scott Richard, M.D., associate professor at the Sidney Kimmel Medical College at Thomas Jefferson University about ovarian cancer recurrence, and what more needs to be done in the field. - See more at: http://www.curetoday.com/articles/ovarian-cancer-recurrence-discussion-with-an-expert?eKey=c2FuZGlwbkBzeW1wYXRpY28uY2E=#sthash.rATXeI8M.dpuf

Quality of life during olaparib maintenance therapy in platinum-sensitive relapsed serous ovarian cancer : British Journal of Cancer

Abstract - BMJ

Background:

Maintenance monotherapy with the poly(ADP-ribose) polymerase inhibitor olaparib significantly prolongs progression-free survival over placebo in patients with platinum-sensitive relapsed serous ovarian cancer, with greatest benefit seen in patients with a BRCA1/2 mutation (BRCAm). Preservation of health-related quality of life (HRQoL) is important during maintenance therapy; we evaluated the effect of olaparib on HRQoL in this Phase II trial (NCT00753545, Study 19).

Methods:

Patients received olaparib 400 mg b.i.d. (capsules) or placebo until progression. Patient-reported HRQoL and disease-related symptoms were evaluated using the FACT-Ovarian (FACT-O) questionnaire (completed at baseline and every 28 days until progression), the FACT/NCCN Ovarian Symptom Index (FOSI) and the Trial Outcome Index (TOI). TOI of the FACT-O was the primary measure.

Results:

Overall, 265 women were randomised to maintenance olaparib (n=136) or placebo (n=129). Compliance for HRQoL assessment was high (~80% over time). Most patients in both arms reported a best response of ‘no change’ on TOI (81%) and other HRQoL measures. There were no statistically significant differences in time to worsening or improvement rates of TOI, FOSI and FACT-O scores in the overall, BRCAm and germline BRCAm populations.

Conclusions:

Maintenance treatment with olaparib was well tolerated and had no adverse impact on HRQoL in this study of patients with platinum-sensitive relapsed serous ovarian cancer who had responded to their most recent platinum-based therapy (partial or complete response). Interpretation of the HRQoL results in this population may differ from patients who have not responded to their most recent platinum-based therapy.

Outcome of patients with advanced ovarian cancer who do not undergo debulking surgery: A single institution retrospective review

abstract
 (IDS = interval debulking surgery) 

Highlights

• •Debulking surgery is not feasible for up to 20% of patients.
• •Chemotherapy alone can allow reasonable disease control in women unsuitable for IDS.
• •Carboplatin plus paclitaxel should be used when possible.

Objective

To assess the outcome of patients with advanced ovarian cancer (OC) who were treated without surgery, having received upfront chemotherapy and no interval debulking surgery (IDS).

Methods

Retrospective analysis of medical and chemotherapy records of consecutive patients with OC between 2005 and 2013 at UCL Hospitals London, UK who received neoadjuvant chemotherapy (NACT) was then found to be unsuitable for IDS following review by the multidisciplinary team.

Results

Eighty-three patients (18%) out of 467 receiving NACT did not undergo IDS. Median age was 70 years (range 33–88); out of these 83 patients, 43 (51.8%) presented with stage IV disease. Forty-three of these 83 patients received carboplatin and paclitaxel (CP) (51.8%) and 37 received carboplatin alone (C) (44.6%); 3 patients (3.6%) received other platinum-based combinations. Reasons for not proceeding to surgery were: poor response to chemotherapy after 3–4 cycles of NACT (61/83, 73.5%); comorbidities (12/83, 14.5%); patient decision (4/83, 4.8%). Six patients (7.2%) received <3 cycles of NACT due to a worsening clinical condition. The median overall survival (OS) for patients not undergoing IDS was 18 months (95% CI 10–20 months). Forty-four of 83 patients (53%) received >2 lines of chemotherapy. In a univariate analysis CP, age <70 years, and absence of comorbidities were factors influencing OS. In a multivariate analysis only having received CP remained independently associated with OS (HR 0.49, 95% CI 0.29–0.84).

Conclusions

Chemotherapy alone can provide reasonable disease control in patients unsuitable for IDS and CP should be used if possible.

Generational Expression of Muir-Torre Syndrome in a Canadian Family - Case Reports in Dermatological Medicine

open access

Case Reports in Dermatological Medicine
Case Report
Generational Expression of Muir-Torre Syndrome in a Canadian Family

 Muir-Torre syndrome (MTS) is a rare autosomal dominant inherited genodermatosis that is considered to be a phenotypic subtype of hereditary nonpolyposis colorectal cancer (HNPCC), commonly referred to as Lynch syndrome....... The case demonstrates that the management of MTS, a potentially underreported syndrome, requires a multiprofessional approach incorporating vigilance, screening, and expert knowledge for successful diagnosis and potentially improved prognosis for patients and their families. The case also demonstrates the varied heritability of MTS and prompts the question of how MTS is expressed in succeeding generations.....

MTS is characterized by at least one cutaneous neoplasm and at least one visceral malignancy [1, 5, 6, 9–11]. Cutaneous neoplasms reported in MTS are of sebaceous etiology, nonspecific clinically, and rarely seen in the general population. Visceral malignancies commonly reported in MTS are of gastrointestinal and genitourinary etiology [3, 5, 7, 12]. MTS is a rare condition with only several hundred cases reported to date [13–15]. The majority of MTS cases are associated with mutations of HMSH2 [5, 15]. We present a case that exemplifies the varied heritability of MTS (in terms of severity and age of onset) in succeeding generations as well as the importance of regular screening, vigilance, and the necessity of a multiprofessional approach for the effective detection and management of this rare and likely underreported condition.

Financial Hardship Common Among Cancer Survivors and Warrants Patient-Provider Discussion

Cancer Therapy Advisor

  Psychological response was also high among cancer survivors. In a study of women with breast or gynecologic cancers, 47% were concerned about lost wages, 68% were concerned about medical costs, and 49% reported financial stress, and, as a result, had poorer functional, emotional, and physical well-being, and were at risk of depression.

Reference

1. Altice CK, Banegas MP, Tucker-Seeley RD, Yabroff KR. Financial hardships experienced by cancer survivors: a systematic review. J Natl Cancer Inst. 2016 Oct 20;109(2). doi: 10.1093/jnci/djw205

Cancer drugs, survival, and ethics

The BMJ

 Survival
A meta-analysis published in 2004 explored the contribution of cytotoxic chemotherapy to five year survival in 250 000 adults with solid cancers from Australian and US randomised trials.3 An important effect was shown on five year survival only in testicular cancer (40%), Hodgkin’s disease (37%), cancer of the cervix (12%), lymphoma (10.5%), and ovarian cancer (8.8%).....

 An unethical pressure to enrol is reflected by several studies showing that up to half of patients in cancer drug trials were led to believe that such participation was their only option.9

 More post-approval “real world” evaluation of cancer drugs would be an important step forward.

Using epigenetics to help the immune system fight ovarian cancer

medical news

Provided by: University of Alabama at Birmingham

(Olaparib/Lynparza) New ovarian cancer drug shown to prolong lives approved for use in Scotland

media

The drug, also known as Lynparza, is already in use in the USA, Europe and England and this week the Scottish Medicines Consortium permitted its use in Scotland.
It will also be used for those with fallopian tube and peritoneal cancers and could eventually treat a wide range of cancer types, including breast and pancreatic cancer.

lncRNAs as novel indicators of patients' prognosis in stage I epithelial ovarian cancer: a retrospective and multicentric study

abstract

Purpose: Stage I epithelial ovarian cancer (EOC) represents about 10% of all EOCs and is characterized by good prognosis with fewer than 20% of patients relapsing. As it occurs less frequently than advanced stage EOC, its molecular features have not been thoroughly investigated. We have demonstrated that in stage I EOC hsa-miR-200c-3p can predict patients' outcome. In the present study, we analyzed the expression of long non-coding RNAs (lncRNAs) to enable potential definition of a non coding transcriptional signature with prognostic relevance for stage I EOC.

Experimental Design: 202 snap-frozen stage I EOC tumor biopsies, 47 of which relapsed, were gathered together from three independent tumor tissue collections and subdivided into a training set (n=73) and a validation set (n=129). Median follow up was 9 years. LncRNAs' expression profiles were correlated in univariate and multivariate analysis with overall survival (OS) and progression free survival (PFS).

Results: The expression of lnc-SERTAD2-3, lnc-SOX4-1, lnc-HRCT1-1 and PVT1 are associated in univariate and multivariate analyses with relapse and poor outcome in both training and validation sets (p<0.001). Using the expression profiles of PVT1, lnc-SERTAD2-3 and hsa-miR-200c-3p simultaneously, it was possible to stratify patients into high and low risk. The OS for high and low risk individuals are 36 and 123 months respectively (OR=15.55).

Conclusions: We have identified a non-coding transcriptional signature predictor of survival and biomarker of relapse for stage I EOC.

Chemotherapy-Induced Constipation and Diarrhea: Pathophysiology, Current and Emerging Treatments

 Abbreviations

CIC, chemotherapy-induced constipation; 

CID, chemotherapy-induced diarrhea; 

ENS, enteric nervous system; 

GI, gastrointestinal.

                                     ~~~~~~~~~~~~~~~~~~~~~~~~~
open access:
Frontiers | Chemotherapy-Induced Constipation and Diarrhea: Pathophysiology, Current and Emerging Treatments | Pharmacology of Anti-Cancer Drugs

 Conclusion

Chemotherapy-induced diarrhea and CIC are amongst the most common chemotherapy-induced GI toxicities, heavily contributing to treatment delays, dose reductions and in some cases cessation of anti-cancer treatment, greatly effecting management and clinical outcomes. Current treatments for CID and CIC are limited and come with a profuse amount of concomitant symptoms; however, novel therapies present a promising avenue of treatment for CID and CIC. Identification of potential targets and the development of novel treatments alleviating chemotherapy-induced toxicity are essential to improve clinical outcomes and quality of life amongst cancer sufferers.

Novel plan to get dying patients a trial cancer drug raises questions

medical news

(ovarian cancer) Retraction Note to: Clinical significance and expression of the PRSS3 and Wiskott–Aldrich syndrome protein family verprolin-homologous protein 1 for the early detection of epithelial ovarian cancer

Retraction Note to: Clinical significance and expression of the PRSS3 and Wiskott–Aldrich syndrome protein family verprolin-homologous protein 1 for the early detection of epithelial ovarian cancer | SpringerLink

A race against time to diagnose deadly weight loss in cancer patients

Medical News

 "We are losing many cancer patients, not because of their cancer, but because their bodies have undergone important metabolic changes. In other words, they have simply stopped functioning correctly. In severe stages of cachexia, weight loss becomes very important and nutrients can no longer be absorbed or used properly by cancer patients," explains Dr. Antonio Vigano, lead author of the paper and Director of the Cancer Rehabilitation Program and Cachexia Clinic of the MUHC. "Cachexia gets worse with time and the longer we wait to address it, the harder it is to treat. Effectively diagnosing cachexia when still in its early stages can make an enormous difference for a cancer patient's prognosis and quality of life. In order to save more lives, we need practical and accessible tools that can be effectively used by clinicians in their routine practice to identify patients with cachexia."

 Article: Use of routinely available clinical, nutritional, and functional criteria to classify cachexia in advanced cancer patients

AMA Store: Code of Medical Ethics of the American Medical Association

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Comprehensive genomic analysis of young adult glioblastomas reveals four subclasses with distinct driver events

abstract
COMPREHENSIVE GENOMIC ANALYSIS OF YOUNG ADULT GLIOBLASTOMAS REVEALS FOUR SUBCLASSES WITH DISTINCT DRIVER EVENTS 

 Glioblastoma (GBM) is the most common primary malignant brain tumor in adults; however, recent studies have shown that GBM is comprised of biologically and genetically distinct diseases which share a common morphologic appearance. In this study, we demonstrate that young adult GBMs (yaGBM, 18-40 years) comprise genomically distinct subclasses with unique collections of driver events. DNA was extracted from 271 yaGBM (female 110, male 161, median age 34 years) samples and comprehensive genomic profiling was performed using hybridization-capture, adaptor ligation-based libraries for 315 cancer-related genes including selected introns from 31 genes frequently rearranged in cancer. The most commonly altered genes were TP53 (65.3%), IDH1 (40.6%), ATRX (40.6%), CDKN2A/B (39.1%/33.6%), PTEN (24.0%), TERT (20.3%), NF1 (18.1%), PIK3CA (17.3%), CDK4 (15.5%), EGFR (14.0%), H3F3A (12.5%), PDGFRA (11.4%), and RB1 (11.4%). Genomic rearrangements included FGFR1-TACC1 (n=2), FGFR2-GKAP1 (n=1), FGFR3-TACC3 (n=2), and BRAF-KIAA1549 (n=1). Unsupervised latent class analysis revealed four distinct classes of yaGBM largely defined as (1) IDH1/TP53 mutant (2) IDH1/TP53 mutant with PDGFRA amplification, (3) H3F3A/TP53 mutant, and (4) PI3K activation (PTEN/EGFR mutant, TP53 wild type). The median tumor mutation burden (TMB) was 3.6 mutations/Mb (range <1 to 666 mutations/Mb). Samples with TMBs ≥ 10 mutations/Mb (n=39, 10.7%) were enriched for genomic alterations involving DNA repair/mismatch repair genes including MSH6 (23.9%), MLH1 (21.7%), ATM (19.6%), MLL2 (15.2%), and MSH2 (13.0%). Taken together these findings demonstrate that yaGBMs can be subdivided into four genetically distinct subclasses each with unique driver events. Furthermore, these findings highlight clinically actionable alterations for which targeted agents are available including IDH1, PIK3CA, PDGFRA, or EGFR inhibitors while a subpopulation of patients with hypermutated GBMs may benefit from immunotherapy agents.

Next-Generation Sequencing and Result Interpretation in Clinical Oncology: Challenges of Personalized Cancer Therapy

abstract
Next-Generation Sequencing and Result Interpretation in Clinical Oncology: Challenges of Personalized Cancer Therapy - Annual Review of Medicine, 68(1)

The tools of next-generation sequencing (NGS) technology, such as targeted sequencing of candidate cancer genes and whole-exome and -genome sequencing, coupled with encouraging clinical results based on the use of targeted therapeutics and biomarker-guided clinical trials, are fueling further technological advancements of NGS technology. However, NGS data interpretation is associated with challenges that must be overcome to promote the techniques’ effective integration into clinical oncology practice. Specifically, sequencing of a patient’s tumor yields 30–65 somatic variants, but most of these variants are “passenger” mutations that are phenotypically neutral and thus not targetable. Therefore, NGS data must be interpreted by multidisciplinary decision-support teams to determine mutation actionability and identify potential “drivers,” so that the treating physician can prioritize what clinical decisions can be pursued in order to provide cancer therapy that is personalized to the patient and his or her unique genome.
Expected final online publication date for the Annual Review of Medicine Volume 68 is January 14, 2017. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

External validation of the pathological nodal staging score in upper tract urothelial carcinoma

abstract:
External validation of the pathological nodal staging score in upper tract urothelial carcinoma: A population-based study - Urologic Oncology: Seminars and Original Investigations
 

Objectives

To externally validate our previously developed pathological nodal staging model (pNSS) that allows quantification of the likelihood that a patient with pathologic node-negative status has, indeed, no lymph node metastasis (LNM).

Patients and methods

We analyzed data from 2,768 patients treated with radical nephroureterectomy (RNU) and lymph node dissection (LND) using the Surveillance, Epidemiology, and End Results database from 1988 to 2010. We estimated the sensitivity of pathologic nodal staging using a beta-binomial model and developed a new pNSS. Then, we compared these findings with those of the initial cohort.

Results

The mean and median numbers of lymph node (LN) removed were 5 and 2, respectively (interquartile range = 5) in the validation cohort, though 66.5% of the patients (n = 1814) were pN0. Similar to the development cohort, the probability of missing a LNM decreased as the number of nodes examined increased in the validation cohort. If only a single node was examined, 35% of patients would be misclassified as pN0 while harboring LNM. Even when 5 nodes were examined, 8% would be misclassified. The probability of having a positive node increased with advancing pathological T stage in both the cohorts. Patients with pT0-Ta-Tis-T1 disease in both cohorts would have more than a 95% chance of a correct pathologic nodal staging with 2 examined nodes. However, if a patient has pT3–T4 disease, more than 12 examined LNs are needed to reach 95% accuracy.

Conclusions

We confirmed that the number of examined nodes needed for adequate staging depends on pT category. We externally validated our previous pNSS in a population-based database, which could help in the clinical decision-making regarding adjuvant chemotherapy administration.

Invasive High-Grade Upper Tract Urothelial Carcinoma in a 14 Year-Old Girl - Urology

Hydronephrosis is the swelling of a kidney due to a build-up of urine. It happens when urine cannot drain out from the kidney to the bladder from a blockage or obstruction. Hydronephrosis can occur in one or both kidneys. The main function of the urinary tract is to remove wastes and fluid from the body.

ne·phrec·to·my nəˈfrektəmē/ noun noun: nephrectomy; plural noun: nephrectomies   surgical removal of one or both of the kidneys.

  

u·re·ter·ec·to·my (yū'rē-tĕr-ek'tŏ-mē) Excision of a segment or all of a ureter.

                          ```````````````````````````````````````````````
abstract

We present an unusual pediatric case of invasive upper tract urothelial carcinoma with an associated genetic predisposition. A 14 year-old female presented with intermittent right flank pain, and was found to have a poorly functioning hydronephrotic right kidney. Laparoscopic nephrectomy was performed. Pathology demonstrated upper tract urothelial carcinoma, and she subsequently underwent completion ureterectomy. Genetic studies demonstrated a double-hit constitutional deletion of a DNA mismatch repair protein, revealing a rare Lynch syndrome variant known as Constitutional Mismatch Repair Deficiency Syndrome (CMMRD). This disease places her at high risk for multiple malignancies, including upper tract urothelial carcinoma.

Keywords:

Pediatrics, upper tract urothelial carcinoma, constitutional mismatch repair deficiency syndrome, Lynch syndrome, mismatch repair, transitional cell carcinoma

open access: Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer

 Bone marrow suppression or myelotoxicity (adjective myelotoxic) or myelosuppression is the decrease in production of cells responsible for providing immunity (leukocytes), carrying oxygen (erythrocytes), and/or those responsible for normal blood clotting (thrombocytes).
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open access — NEJM
November 7, 2016

Patients
The first patient was enrolled on August 26, 2013. The database for the current analysis was locked on June 20, 2016, and follow-up is ongoing. A total of 553 patients were enrolled in the study at 107 sites in the ENGOT countries, the United States, Canada, and Hungary. Of these patients, 201 received treatment in the gBRCA cohort and 345 in the non-gBRCA cohort (Figure 1Figure 1Enrollment and Outcomes.). At the time of the database lock, 51 patients in the gBRCA cohort and 58 in the non-gBRCA cohort were still receiving niraparib or placebo.
 In conclusion, the duration of progression-free survival in patients with platinum-sensitive, recurrent ovarian cancer was significantly longer in the niraparib group than in the placebo group, regardless of the presence or absence of gBRCA mutations or HRD status. The treatment-associated myelotoxicity required dose modifications or delays but was not associated with a long-term increase in mortality or morbidity.


....Overall, the niraparib side-effect profile was consistent with that in previous studies, and adverse events were managed with appropriate dose modifications and delays. Although grade 3 or 4 hematologic abnormalities were common, the low incidence of discontinuation because of such events (9.3%) (Table S4 in the Supplementary Appendix) and the absence of cumulative thrombocytopenia show the effectiveness of dose modifications. Notably, patient-reported outcomes were similar in the niraparib group and the placebo group, indicating that niraparib did not adversely affect the patients’ quality of life over the course of treatment.

In conclusion, the duration of progression-free survival in patients with platinum-sensitive, recurrent ovarian cancer was significantly longer in the niraparib group than in the placebo group, regardless of the presence or absence of gBRCA mutations or HRD status. The treatment-associated myelotoxicity required dose modifications or delays but was not associated with a long-term increase in mortality or morbidity.