A non-randomized confirmatory study regarding selection of fertility-sparing surgery for patients with epithelial ovarian cancer: Japan Clinical Oncology Group

Abstract

 Fertility-sparing treatment has been accepted as a standard treatment for epithelial ovarian cancer in stage IA non-clear cell histology grade 1/grade 2. In order to expand an indication of fertility-sparing treatment, we have started a non-randomized confirmatory trial for stage IA clear cell histology and stage IC unilateral non-clear cell histology grade 1/grade 2. The protocol-defined fertility-sparing surgery is optimal staging laparotomy including unilateral salpingo-oophorectomy, omentectomy, peritoneal cytology and pelvic and para-aortic lymph node dissection or biopsy. After fertility-sparing surgery, four to six cycles of adjuvant chemotherapy with paclitaxel and carboplatin are administered. We plan to enroll 250 patients with an indication of fertility-sparing surgery, and then the primary analysis is to be conducted for 63 operated patients with pathologically confirmed stage IA clear cell histology and stage IC unilateral non-clear cell histology grade 1/grade 2. The primary endpoint is 5-year overall survival. Secondary endpoints are other survival endpoints and factors related to reproduction. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000013380.

Early Alopecia May Signal Chemo Response in Ovarian Cancer

 Cancer Network

 ......When adjusting for the common clinicopathologic features such as postoperative tumor residuals, histology, and FIGO stage, early-onset—up to cycle 4—grade 2 alopecia appeared to significantly correlate with a more favorable OS,” the researchers wrote. “It needs to be further elucidated whether early-onset alopecia is just a surrogate marker for higher sensitivity to chemotherapy and hence associated with a longer survival or if other unidentified biological pathways are underlying that correlate alopecia with cytotoxicity and survival.”

Intraperitoneal Chemo Ups 10-Year Ovarian Cancer Survival

Cancer Network

Epidemiology and risk factors of bladder and urothelial tumors

Blogger's Note: not included in this abstract is the risk for Lynch syndrome mutation carriers (MSH2)

Epidemiology and risk factors of bladder and urothelial tumors - Abstract
    Published: 25 March 2015

Bladder cancer is the 5th most commonly diagnosed cancer in France, and most of cases occur in men and patients aged more than 65 years.
The incidence and mortality are declining except in women in whom the incidence is increasing in recent years. Urothelial tumors of the upper urinary tract are less common but have similar aetiology to the bladder tumours. The recurrent aspect of superficial tumors and the morbidity of invasive tumors are an economic burden in the Western health systems. The two main risk factors for urothelial tumors are tobacco smoking and occupational exposure to chemicals carcinogens such as polycyclic aromatic hydrocarbons, nitrosamines, aromatic amines and arsenic. Other risk factors include urinary schistosomiasis, pelvic radiation therapy, the use of cyclophosphamide and probably diet and lifestyle factors. Prevention of bladder tumors is based on the control of these risk factors and individual screening in high-risk patients. Recognition as an occupational disease is an important part of the social management of patient, which is today inadequately performed.

Menopausal Hormone Therapy and Risk for Ovarian Cancer

Medscape

OPEN ACCESS: Hereditary predisposition to ovarian cancer, looking beyond BRCA1/BRCA2

full text - open access published Jan 2015


 

Gynecologic Oncology April 2015 index of articles

issue index



http://ovariancancerandus.blogspot.com/feeds/posts/default

A phase II evaluation of the potent, highly selective PARP inhibitor veliparib in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who carry a germline BRCA 1/2

Abstract


Highlights
•
    Veliparib demonstrated single agent activity among recurrent ovarian cancer patients carrying a germline BRCA1/2 mutation
•
    Adverse events were observed but generally mild and managed conservatively
•
    Clinical responses were observed among enrolled with platinum-sensitive and -resistant recurrent disease

Background
Veliparib is a potent small molecule inhibitor of PARP-1/2, which is cytotoxic in tumor cells with deficiencies in BRCA1 or BRCA2. We studied the clinical activity and toxicity of veliparib in ovarian cancer patients carrying a germline BRCA1 or BRCA2 mutation (gBRCA).
Methods
Eligibility included three or fewer prior chemotherapy regimens, measurable disease and no prior use of a PARP inhibitor. Veliparib was administered at 400 mg orally BID with one cycle being 28 days. The two-stage Simon design was capable of detecting a 25% response probability with 90% power while controlling alpha=10% (at a 10% assumed null response probability).
Results
The median age of the 50 eligible patients was 57 years (range 37–94) and 14, 18, and 18 patients had 1, 2, and 3 prior therapies respectively. Thirty patients (60%) were platinum-resistant. The median number of cycles administered was 6 (1-27). There was one grade 4 thrombocytopenia. Grade 3 adverse events were: fatigue (n=3), nausea (2), leukopenia (1), neutropenia (1), dehydration (1), and ALT (1). Grade 2 events > 10% were: nausea (46%), fatigue (26%), vomiting (18%), and anemia (14%). The proportion responding was 26% (90% CI: 16%-38%, CR:2, PR:11); for platinum-resistant and platinum-sensitive patients the proportion responding was 20% and 35%, respectively. The most common reason for treatment discontinuation was progression (62%). Twenty-nine patients are alive; two with SD remain on veliparib. The median PFS is 8.18 months.
Conclusions
The single agent efficacy and tolerability of veliparib for BRCA mutation-associated recurrent ovarian cancer warrants further investigation.

Keywords
    veliparib;
    ovarian cancer;
    PARP inhibitor;
    toxicity;
    Phase II trial;
    BRCA1, BRCA2 mutation

Immunotherapeutic approaches to ovarian cancer treatment

Abstract

J Immunother Cancer. 2015 Mar 24;3:7. doi: 10.1186/s40425-015-0051-7. eCollection 2015.

Immunotherapeutic approaches to ovarian cancer treatment.
Chester C1, Dorigo O2, Berek JS2, Kohrt H1.
Author information
    1Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA USA.
    2Stanford Women's Cancer Center, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305 U.S.A.

Abstract
Despite advances in combinatorial chemotherapy regimens and the advent of intraperitoneal chemotherapy administration, current therapeutic options for ovarian cancer patients are inadequate. Immunotherapy offers a novel and promising therapeutic strategy for treating ovarian tumors. Following the demonstration of the immunogenicity of ovarian tumors, multiple immunotherapeutic modalities have been developed. Antibody-based therapies, immune checkpoint blockade, cancer vaccines, and chimeric antigen receptor-modified T cells have demonstrated preclinical success and entered clinical testing. In this review, we discuss these promising immunotherapeutic approaches and emphasize the importance of combinatorial treatment strategies and biomarker discovery.

KEYWORDS:

ACT; Antibody; Cancer vaccine; ID8; IDO; Immune checkpoint blockade; Ovarian cancer; TAM

Considerations and management of a patient with three metachronous cancers in association with Lynch syndrome and ileal Crohn's disease: A case report

abstract


INTRODUCTION:
Lynch syndrome and Crohn's disease are two entirely separate conditions but each have major gastrointestinal characteristics and carry a substantial increase in the risk of intestinal malignancy. Their co-existence in the patient who is the subject of this report dictated the need for an individualised treatment plan to deal with both conditions adequately.
PRESENTATION OF CASE:
We report a case of a 51 year old female with a past medical history that includes Lynch syndrome and small bowel Crohn's disease. Over a period of fifteen months, she developed three separate primary metachronous tumors in her endometrium, colon and duodenum.
DISCUSSION:
A patient with a combination of Lynch syndrome and ileal Crohn's disease presents significant therapeutic implications that are not usually present when these conditions are treated in isolation.
CONCLUSION:
The surgical treatment of patients with Lynch syndrome requires a sound knowledge of the possible neoplastic conditions that can arise in the syndrome. Early detection is paramount, either by implementation of evidence based surveillance programs or at least by a heightened clinical awareness of the features of this disease. Ideally this will result in both reduced surgical morbidity and improved oncologic outcome. Furthermore, the medical treatment of Crohn's disease in a patient with tumors arising from Lynch syndrome must be undertaken with at least a consideration of the possibility that the use of immunosuppressive medication might increase the risk of cancer recurrence.

Decisions about prophylactic gynecologic surgery: a qualitative study of the experience of female Lynch syndrome mutation carriers

Abstract

BACKGROUND:
Women who carry a mutation for Lynch syndrome face complex decisions regarding strategies for managing their increased cancer risks. At present, there is limited understanding of the factors influencing women's prophylactic surgery decisions.
METHODS:
As part of an exploratory pilot project, semi-structured interviews were conducted with 10 women who were Lynch syndrome mutation carriers and had made prophylactic surgery decisions. Nine of 10 women had chosen to undergo prophylactic hysterectomy and/or oophorectomy as a means of managing their increased gynecological cancer risks.
RESULTS:
Study findings revealed that surgery decisions were influenced by multiple factors, including demographic variables such as age and parity, as well as psychosocial factors such as cancer worry, in addition to personal and social knowledge of gynecological cancer. While all women were satisfied with their surgery decision, some reported they were not fully informed about the negative impact on their quality of life post-surgery (e.g., complications of surgically-induced menopause), nor about the potential for, or risks and benefits of, hormone replacement therapy.
CONCLUSIONS:
Study findings highlight some of the factors associated with prophylactic surgery decisions and women's perceptions about pre-surgical information provision and needs. Suggestions are made for improving the information and support provided to female carriers of a Lynch syndrome mutation

Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies - The Lancet

open access (click on pdf)

Abstract/Full text

 Summary

Background

Half the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therapy on ovarian cancer risk.

Methods

Individual participant datasets from 52 epidemiological studies were analysed centrally. The principal analyses involved the prospective studies (with last hormone therapy use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies. Adjusted Poisson regressions yielded relative risks (RRs) versus never-use.

Findings

During prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with <5 years of use (RR 1·43, 95% CI 1·31–1·56; p<0·0001). Combining current-or-recent use (any duration, but stopped <5 years before diagnosis) resulted in an RR of 1·37 (95% CI 1·29–1·46; p<0·0001); this risk was similar in European and American prospective studies and for oestrogen-only and oestrogen-progestagen preparations, but differed across the four main tumour types (heterogeneity p<0·0001), being definitely increased only for the two most common types, serous (RR 1·53, 95% CI 1·40–1·66; p<0·0001) and endometrioid (1·42, 1·20–1·67; p<0·0001). Risk declined the longer ago use had ceased, although about 10 years after stopping long-duration hormone therapy use there was still an excess of serous or endometrioid tumours (RR 1·25, 95% CI 1·07–1·46, p=0·005).

Interpretation

The increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for 5 years from around age 50 years have about one extra ovarian cancer per 1000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1700 users.

breaking news: Canadians have right to doctor-assisted suicide, Supreme Court rules

breaking news - The Globe and Mail

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• Health care Canadian doctors drafting new rules in case doors open to assisted suicide

Infertility in reproductive-age female cancer survivors

abstract

 Improved survival rates among reproductive-age females diagnosed with cancer have increased the focus on long-term quality of life, including maintenance of the ability to conceive biological children. Cancer-directed therapies such as high-dose alkylating agents and radiation to the pelvis, which deplete ovarian reserve, radiation to the brain, which affects the hypothalamic-pituitary-gonadal axis, and surgical resection of reproductive structures can decrease the likelihood of having biological children. Standard fertility preservation strategies such as embryo and oocyte cryopreservation before the onset of therapy offer the opportunity to conserve fertility, but they may not be feasible because of the urgency to start cancer therapy, financial limitations, and a lack of access to reproductive endocrinologists. Ovarian tissue freezing is considered experimental, with limited data related to pregnancies, but it minimizes treatment delay. Studies evaluating gonadotropin-releasing hormone analogues have had mixed results, although a recent randomized, prospective study in women with breast cancer demonstrated a protective effect. Fertility preservation programs are increasingly being developed within cancer programs. In this article, we describe risks to infertility and options for preservation, raise psychosocial and ethical issues, and propose elements for establishing an effective fertility preservation program.

(AICR): CRU: New Survey: Low Awareness of Key Cancer Risk Factors

 

New Survey

Current unmet needs of cancer survivors: Analysis of open-ended responses to the ACS Study of Cancer Survivors II

abstract

BACKGROUND

Cancer survivors may continue to experience psychosocial and physical needs related to their cancer experience for many years after treatment. The specification of these needs across cancer types and by survivor characteristics may lead to better prevention approaches and clinical responses. Mixed methods were used to examine responses to an open-ended question about current unmet needs from a survey of 2-, 5-, and 10-year cancer survivors.

METHODS

Qualitative techniques were used to code themes of unmet needs from open-ended responses. These themes were then examined with quantitative techniques to describe the frequency of unmet needs across disease subgroups and demographic subgroups of survivors.

RESULTS

There were 1514 responses to the open-ended question on unmet needs. Respondents ranged in age from 24 to 97 years and included proportionately more women, and 18% were minorities (black and Hispanic). Sixteen themes of unmet needs were identified. The number and type of unmet needs were not associated with the time since cancer treatment. Breast cancer survivors identified more unmet needs than other survivors. Male survivors and especially prostate cancer survivors identified personal control problems as current needs. Older cancer survivors identified fewer unmet needs on average than younger survivors.

CONCLUSIONS

This analysis of an open-ended question on unmet needs extends our understanding of how cancer survivors perceive problems related to cancer. How cancer-related needs change over time and differ by sex, race, and ethnicity and how problems with personal control become manifest are areas of inquiry requiring further research. 

Comparison of oncology drug approval between Health Canada and the US Food and Drug Administration

abstract

BACKGROUND

The drug approval timeline is a lengthy process that often varies between countries. The objective of this study was to delineate the Canadian drug approval timeline for oncology drugs and to compare the time to drug approval between Health Canada (HC) and the US Food and Drug Administration (FDA).

METHODS

In total, 54 antineoplastic drugs that were approved by the FDA between 1989 and 2012 were reviewed. For each drug, the following milestones were determined: the dates of submission and approval for both the FDA and HC (Health Canada) and the dates of availability on provincial drug formularies in Canadian provinces and territories. The time intervals between the aforementioned milestones were calculated.

RESULTS

Of 54 FDA-approved drugs, 49 drugs were approved by HC at the time of the current study. The median time from submission to approval was 9 months (interquartile range [IQR], 6-14.5 months) for the FDA and 12 months (IQR, 10-21.1 months) for HC (P < .0006). The time from HC approval to the placement of a drug on a provincial drug formulary was a median of 16.7 months (IQR, 5.9-27.2 months), and there was no interprovincial variability among the 5 Canadian provinces that were analyzed (P = .5).

CONCLUSIONS

The time from HC submission to HC approval takes 3 months longer than the same time interval for the FDA. To the authors' knowledge, this is the first documentation of the time required to bring an oncology drug from HC submission to placement on a provincial drug formulary.

Trends in gynaecological cancers in the largest obstetrics and gynaecology hospital in China from 2003 to 2013I

abstract

The incidence and the trend of gynaecological cancers have been suggested to vary by ethnicity and geographical regions. Whether the incidence and type of gynaecological cancers in China is different have not been fully investigated. In this study, we reported the trend of gynaecological cancers in China. Data on 13,518 women with gynaecological cancers were collected from the largest obstetrics and gynaecology hospital in China from 2003 to 2013. Data included age at diagnosis and the annual number of women with diagnosed endometrial, ovarian, cervical cancer and other gynaecological cancers. The number of women with diagnosed gynaecological cancers increased by almost sixfold in 2013 compared to that in 2003. It was largely due to the increase of women with newly diagnosed cervical cancer. The percentage of women with endometrial and ovarian cancer within total gynaecological cancers was decreased, whilst the percentage of cervical cancer significantly increased between 2003 and 2013. The mean age of women with endometrial or ovarian cancer at diagnosis was 53 or 48 years, respectively, which was no difference over 11 years. However, the mean age of women with cervical cancer at diagnosis was significantly delayed from 42 years in 2003 to 46 years since 2011. This was also confirmed by the age-specific distribution of gynaecological cancers over 11 years. Our study found that the age onset of endometrial and ovarian cancer has not changed over 11 years. But the age onset of cervical cancer is delayed since 2011 in China.

Microbiology of Pelvic Lymphocyst Infection after Lymphadenectomy for Malignant Gynecologic Tumors

abstract

 Background: Pelvic lymphocyst infection is a rare complication after lymphadenectomy for malignant gynecologic tumors. Although medical therapy is a useful addition to surgical drainage, the appropriate antibiotic regimen is unknown because few studies have examined the causative organisms. The purpose of this case series was to identify the micro-organisms infecting pelvic lymphocysts.

Methods: This was a single-center, retrospective, case-series review conducted at a tertiary-care cancer center between October 2002 and March 2013. The participants included all patients who experienced their first pelvic lymphocyst infection after undergoing pelvic lymphadenectomy for cervical, endometrial, or ovarian cancer and exhibited positive lymphocyst fluid culture. Computed tomography- or sonography-guided percutaneous aspiration procedures were performed to obtain lymphocyst fluid for culture.

Results: During the study period, 878 patients underwent lymphadenectomy for gynecologic malignant tumors, and 13 developed a pelvic lymphocyst infection documented microbiologically. Cultures identified Staphylococcus aureus (three patients), S. epidermidis (one patient), Streptococcus agalactiae (three patients), Enterococcus (two patients), Escherichia coli (one patient), and anaerobic bacteria (three patients). They were all monomicrobial infections.

Conclusions: Our study and other smaller ones suggest that lymphocyst infections following pelvic lymphadenectomy for malignant gynecologic tumors usually are monomicrobial and caused by gram-positive cocci, including Staphylococcus, Streptococcus, and Enterococcus, and anaerobes such as Bacteroides fragilis. These bacteria should be considered when selecting empiric antibiotic therapy.

Immunotherapy for Ovarian Cancer (paywalled)

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OPINION STATEMENT:

All work referenced herein relates to treatment of epithelial ovarian carcinomas, as their treatment differs from ovarian germ cell cancers and other rare ovarian cancers, the treatments of which are addressed elsewhere. Fallopian tube cancers and primary peritoneal adenocarcinomatosis are also generally treated as epithelial ovarian cancers. The standard of care initial treatment of advanced stage epithelial ovarian cancer is optimal debulking surgery as feasible plus chemotherapy with a platinum plus a taxane agent. If this front-line approach fails, as it too often the case, several FDA-approved agents are available for salvage therapy. However, because no second-line therapy for advanced-stage epithelial ovarian cancer is typically curative, we prefer referral to clinical trials as logistically feasible, even if it means referring patients outside our system. Immune therapy has a sound theoretical basis for treating carcinomas generally, and for treating ovarian cancer in particular. Advances in understanding the immunopathogenic basis of ovarian cancer, and the immunopathologic basis for prior failures of immunotherapy for it and other carcinomas promises to afford novel treatment approaches with potential for significant efficacy, and reduced toxicities compared with cytotoxic agents. Thus, referral to early phase immunotherapy trials for ovarian cancer patients that fail conventional treatment merits consideration.

Are we winning the war on cancer? The old suffer more than they should

Commentary


In 1971 Richard Nixon declared “War on Cancer” with the signing of the National Cancer Act. Significant progress has been made in the intervening 44 years – and Europe has been at the forefront of many of the advances.
But on February 4, World Cancer Day, it is worth asking whether we are winning the war on a disease which affects more than 22m people annually?......

Spatial Analysis of Advanced-Stage Ovarian Cancer Mortality in California

abstract

def: spatial

OBJECTIVE:

To determine the impact of geographic location on advanced-stage ovarian cancer mortality in relation to adherence to National Comprehensive Cancer Network (NCCN) treatment guidelines and hospital case volume.

STUDY DESIGN:

Retrospective observational cohort study of patients diagnosed with stage IIIC/IV epithelial ovarian cancer (1/1/96-12/31/06) identified from the California Cancer Registry. Generalized additive models were created to assess the effect of spatial distributions of geographic location, demographic characteristics, disease-related variables, adherence to NCCN guidelines, and hospital case volume, with simultaneous smoothing of geographic location and adjustment for confounding variables.

RESULTS:

A total of 11,765 patients were identified. Twelve of the 378 hospitals (3.2%) were high-volume hospitals (≥20 cases/year, HVH) and cared for 2,112 patients (17.9%). For all patients, the median distance to a HVH was 22.7km/14.1mi and 80% were located within 79.6km/49.5mi of a HVH. Overall, 45.4% of patients were treated according to NCCN guidelines. The global test for location revealed that geographic position within the state was significantly correlated with ovarian cancer mortality after adjusting for other variables (p<0.001). Distance to receive care ≥32km/20mi was protective against mortality (HR=0.86, 95%CI=0.79-0.93), while distance from a HVH ≥80km/50mi was associated with an increased risk of death (HR=1.13, 95%CI=1.03-1.23). The effects of geographic predictors were attenuated when non-adherence to NCCN guidelines (HR=1.25, 95%CI=1.18-1.32) and care at a HVH (HR=0.87, 95%CI=0.81-0.93) were introduced into the model.

CONCLUSIONS:

Geographic location is a significant predictor of advanced-stage ovarian cancer mortality and the effect is primarily related to the likelihood of receiving NCCN guideline adherent care and treatment at a HVH.

Identification of rare germline copy number variations over-represented in five human cancer types

open access

".... Results  We explored the germline CNVs (copy number variations) in five cancer cohorts from the Cancer Genome Atlas (TCGA) consisting of 351 brain, 336 breast, 342 colorectal, 370 renal, and 314 ovarian cancers, genotyped on Affymetrix SNP6.0 arrays.....

 ......Many of these loci are new and in some cases are associated with a substantial increase in disease risk......

Research describes new way of shrinking ovarian cancer tumors, improving drug delivery

medical news

 New research published in the February 2015 issue of The FASEB Journal, may eventually help improve the five-year survival rate of ovarian cancer patients by describing a new way of shrinking ovarian cancer tumors while also simultaneously improving drug delivery. This new method involves the use of a portion of a naturally occurring protein inhibitor of angiogenesis called thrombospondin-1 or TSP-1. The portion, known as 3TSR, interacts with another protein called CD36 causing cells needed for tumors to create new blood vessels (endothelial cells) to stop growing and die. In turn, this reduces the formation of new blood vessels (angiogenesis) needed for tumors to grow......

World Cancer Day 2015 | WCD

World Cancer Day 2015 | WCD

Pediatric ovarian neoplastic tumors: incidence, age at presentation, tumor markers and outcome

abstract

OBJECTIVE:

To investigate the incidence, age of onset and tumor marker levels in benign and malignant pediatric ovarian neoplastic tumors. Design. Retrospective database study.

SETTING:

Single center study.

POPULATION:

Forty-five 0-15 year old patients operated on for ovarian neoplastic tumors from the beginning of 1999 to the end of 2013.

METHODS:

Serum alpha-fetoprotein, human chorionic gonadotropin and cancer antigen-125 levels as well as follow-up data were recorded from patient charts and tumor histology was re-evaluated.

MAIN OUTCOME MEASURES:

Incidence of ovarian neoplastic tumors in the pediatric population. Differences in patient characteristics and tumor marker levels between those with benign and malignant tumors.

RESULTS:

The annual incidence of ovarian tumors was 2.2/100 000 females. Median age at presentation was 13.0 years (range 0.9-15.7), similar in both the 33 (73%) with a benign and the 12 patients (27%) with a malignant tumor. The tumors with the highest propensity to metastase (yolk sac tumors, mixed germ cell tumors, small cell carcinoma) were only found in girls >9 years. Elevated serum alpha-fetoprotein and cancer antigen-125 values associated more often with malignant tumors (p<0.001 and 0.031, respectively). There were no deaths or local recurrences. Four patients with a mature teratoma developed a contralateral benign ovarian tumor during follow-up.

CONCLUSIONS:

Both benign and malignant ovarian tumors are rare in the pediatric population, but the incidence increases with age. High alpha-fetoprotein and cancer antigen-125 levels were associated with malignant tumors. The prognosis of the pediatric ovarian tumors seems to be favorable.

Assessment of a new system for primary site assignment in high-grad... - PubMed - NCBI

Abstract

AIMS: 

Evidence indicates that most non-uterine high-grade serous carcinomas (HGSC) arise from the fallopian tube, but approaches to primary site assignment have not evolved to reflect this. This study aimed to assess application of recently proposed criteria for site assignment.

METHODS AND RESULTS:

151 HGSCs from four centres were reviewed retrospectively. 63/80 (79%) chemo-naïve (CN) and 45/71 (68%) post-neoadjuvant chemotherapy (NACT) cases were assigned as fallopian tube (FT) primaries with the new criteria, while 58/80 (73%) and 45/71 (63%) were considered ovarian primaries using traditional criteria (p<0.0001). In 111 prospectively collected HGSC's, with consistent detailed fimbrial examination, 44/53 (83%) CN and 44/58 (76%) NACT cases were assigned as FT primaries. Reproducibility of site assignment was tested in a subset of 50 cases: 4/4 reviewing pathologists agreed on primary site in 48/50 (96%), and 3/4 in 49/50 (98%) cases. Of the 53 prospectively studied CN cases, bilateral ovarian involvement (62%) was significantly more frequent than bilateral tubal involvement (12%, p<0.0001), further supporting tubal origin and ovarian metastasis in most cases.

CONCLUSIONS:

With currently accepted protocols, the proposed guidelines are easy to apply and result in consistent site assignment in non-uterine HGSC. Most cases of non-uterine HGSC were considered primary FT neoplasms

Survival Advantage Associated with Decrease in Stage at Detection from Stage IIIC to Stage IIIA Epithelial Ovarian Cancer

abstract/open access

Objective.
The aim of this study was to document the survival advantage of lowering stage at detection from Stage IIIC to Stage IIIA epithelial ovarian cancer.

Methods.
Treatment outcomes and survival were evaluated in patients with Stage IIIA and Stage IIIC epithelial ovarian cancer treated from 2000 to 2009 at the University of Kentucky Markey Cancer Center (UKMCC) and SEER institutions.

Results. Cytoreduction to no visible disease  and complete response to platinum-based chemotherapy occurred more frequently in Stage IIIA than in Stage IIIC cases. Time to progression was shorter in patients with Stage IIIC ovarian cancer than in those with Stage II1A disease. Five-year overall survival (OS) improved from 41% in Stage IIIC patients to 60% in Stage IIIA patients treated at UKMCC and from 37% to 56% in patients treated at SEER institutions for a survival advantage of 19% in both data sets. 53% of Stage IIIA and 14% of Stage IIIC patients had NED at last followup.

Conclusions. Decreasing stage at detection from Stage IIIC to stage IIIA epithelial ovarian cancer is associated with a 5-year survival advantage of nearly 20% in patients treated by surgical tumor cytoreduction and platinum-based chemotherapy.

 Table 1: Definitions of Stage IIIA and Stage IIIC ovarian cancer*.

Stage III     
Tumor involves one or both ovaries with cytologically or histologically confirmed spread to the peritoneum outside the pelvis and/or metastasis to the retroperitoneal lymph nodes.     
 
Stage IIIA     
  Microscopic metastasis beyond the pelvis.     
 
Stage IIIC     
  Macroscopic, extrapelvic, peritoneal metastasis >2 cm in the greatest dimension and/or regional lymph node metastasis.
     
From Edge et al. [6].

 1. Introduction

Despite advances in radical surgery, postoperative care, and chemotherapy, ovarian cancer remains the leading cause of gynecologic cancer mortality among women in the United States. This year, over 14,000 deaths from ovarian cancer will be reported in the United States alone [1]. Most women continue to present with advanced disease where the cost of treatment is high and survival is low. Since the 5-year survival of patients with early stage ovarian cancer is excellent, many investigators believe that the most effective way to reduce ovarian cancer mortality is through earlier detection. It has been estimated that if 75% of ovarian cancer cases were detected with early stage disease, the number of women dying of this cancer could be reduced by one half.....

Communicating with Biobank Participants: Preferences for Receiving and Providing Updates to Researchers

abstract

Background Research biobanks collect biological samples and health information. Previous work shows that biobank participants desire study updates, but preferences regarding the method or frequency of these communications have not been explored. Thus, we surveyed participants in a long-standing research biobank.

Methods Eligible participants were drawn from a study of patients with personal/family history suggestive of Cowden syndrome, a poorly-recognized inherited cancer syndrome. Participants gave blood samples and access to medical records and received individual results but had no other study interactions. The biobank had 3618 participants at sampling. Survey eligibility included age >18 years, enrollment within the biobank's first five years, normal PTEN analysis, and contiguous United States address. Multivariate logistic regression analyses identified predictors of participant interest in internet-based vs. offline methods and methods allowing participant-researcher interaction vs. one-way communication. Independent variables were narrowed by independent Pearson correlations by cutoff p<0.2, with p<0.02 considered significant.

Results Surveys were returned from 840/1267 (66%) eligible subjects. Most (97%) wanted study updates with 92% wanting updates at least once a year. Participants preferred paper (66%) or emailed (62%) newsletter methods with 95% selecting one of these. Older, less-educated, and lower-income respondents strongly preferred offline approaches (p<0.001). Most (93%) had no concerns about receiving updates and 97% were willing to provide health updates to researchers.

Conclusion Most participants were comfortable receiving and providing updated information. Demographic factors predicted communication preferences. Impact Researchers should make plans for ongoing communication early in study development and funders should support the necessary infrastructure for these efforts.

Utah Ovarian Cancer Alliance | Not all Cancers are Pink

Utah Ovarian Cancer 

World Health Organization’s advice based on weak evidence

 media

Scientific mysteries we could solve in the 21st century (cancer and luck)

Business Insider

 6. Genes, cancer and luck

You might have read recently that most cancer is caused by bad luck, as a study published in Science supposedly concluded. (Actually, the study concluded that the disparity in prevalence of cancer of various types was largely due to luck.) A firestorm of protest followed, essentially based on the belief that such a study must be wrong because it would “send the wrong message” to the public. Proving the illogic of that syllogism should be left as an exercise for the reader.
Other responses revealed that experts do not agree on how random mutations (bad luck) compare with heredity (parent’s fault) plus lifestyle (your fault) and environmental exposure to bad things (somebody else’s fault) in causing cancer. Sorting all that out, and in the process solving cancer’s other mysteries, should be a high-priority exercise for 21st century science. And yes, there is a considerable amount of research relating game theory to cancer.

Read more: https://www.sciencenews.org/blog/context/top-10-scientific-mysteries-21st-century#ixzz3QahPDw3B

A Unique Subset of Epithelial Ovarian Cancers with Platinum Sensitivity and PARP Inhibitor Resistance

Abstract


Platinum and PARP inhibitor (PARPi) sensitivity commonly coexist in epithelial ovarian cancer (EOC) due to the high prevalence of alterations in the homologous recombination (HR) DNA repair pathway that confer sensitivity to both drugs. In this report, we describe a unique subset of EOC with alterations in another DNA repair pathway, the nucleotide excision repair (NER) pathway, which may exhibit a discordance in sensitivities to these drugs. Specifically, 8% of high-grade serous EOC from The Cancer Genome Atlas dataset exhibited NER alterations, including nonsynonymous or splice site mutations and homozygous deletions of NER genes. Tumors with NER alterations were associated with improved overall survival (OS) and progression-free survival (PFS), compared with patients without NER alterations or BRCA1/2 mutations. Furthermore, patients with tumors with NER alterations had similar OS and PFS as BRCA1/2-mutated patients, suggesting that NER pathway inactivation in EOC conferred enhanced platinum sensitivity, similar to BRCA1/2-mutated tumors. Moreover, two NER mutations (ERCC6-Q524* and ERCC4-A583T), identified in the two most platinum-sensitive tumors, were functionally associated with platinum sensitivity in vitro. Importantly, neither NER alteration affected HR or conferred sensitivity to PARPi or other double-strand break-inducing agents. Overall, our findings reveal a new mechanism of platinum sensitivity in EOC that, unlike defective HR, may lead to a discordance in sensitivity to platinum and PARPi, with potential implications for previously reported and ongoing PARPi trials in this disease.

Cancer Res; 75(4); 1-7. ©2014 AACR.
©2014 American Association for Cancer Research

Gynecologic Cancer Imaging with MRI, FDG PET-CT and PET-MRI

abstract

Abstract

MRI and FDG PET-CT play central and complementary roles in gynecologic cancer care. Because treatment often requires combinations of surgery, radio- and chemotherapy, imaging is central to triage and to determine prognosis. This article reviews the use of the two imaging modalities in the initial evaluation of the common cancers --- uterine cervical, uterine endometrial and epithelial ovarian cancers. Imaging features that impact on management and the relative strengths and weaknesses of the two modalities are highlighted. Use of imaging after initial therapy to assess for recurrence and to plan salvage therapy is described. Newer functional and molecular techniques in MRI and PET are evaluated. Finally, we describe our initial experience with PET-MRI, an emerging technology that may prove to be a mainstay in personalized gynecologic cancer care and adaptive therapy.

Copyright © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Coffee, tea, and caffeine consumption and risk of epithelial ovarian cancer and borderline ovarian tumors: Results from a Danish case-control study

abstract

Background. Epidemiological studies that have investigated the association between coffee, tea and caffeine consumption and ovarian cancer risk have produced conflicting results. Furthermore, only few studies have examined the role of coffee and tea consumption separately for borderline ovarian tumors...........

 Conclusions. Our results indicate that coffee consumption and total caffeine consumption from coffee and tea combined is associated with a modest decreased risk of ovarian cancer. However, more biological studies are needed to identify bioactive chemical compounds in coffee that potentially could affect ovarian cancer development.

GINA, Genetic Discrimination, and Genomic Medicine — NEJM

open access

  ....As all medicine in a sense becomes genomic medicine, perhaps the genetic nondiscrimination secured by GINA will translate into nondiscrimination in all of medicine.

Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update 2014

pdf

Purpose
To provide current recommendations about the prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer.
Methods
PubMed and the Cochrane Library were searched for randomized controlled trials, systematic reviews, meta-analyses, and clinical practice guidelines from November 2012 through July 2014. An update committee reviewed the identified abstracts.
Results
Of the 53 publications identified and reviewed, none prompted a change in the
2013 recommendations.
Recommendations
Most hospitalized patients with active cancer require thromboprophylaxis throughout hospitalization. Routine thromboprophylaxis is not recommended for patients with cancer in the outpatient setting. It may be considered for selected high-risk patients. Patients with multiple myeloma receiving antiangiogenesis agents with chemotherapy and/or dexamethasone should receive prophylaxis with either low–molecular weight heparin (LMWH) or low-dose aspirin. Patients undergoing major surgery should receive prophylaxis starting before surgery and continuing for at
least 7 to 10 days. Extending prophylaxis up to 4 weeks should be considered in those undergoing major abdominal or pelvic surgery with high-risk features. LMWH is recommended for the initial 5 to 10 days of treatment for deep vein thrombosis and pulmonary embolism as well as for long-term secondary prophylaxis (at least 6 months). Use of novel oral anticoagulants is not currently recommended for patients with malignancy and VTE because of limited data in patients with cancer. Anticoagulation should not be used to extend survival of patients with cancer in the
absence of other indications. Patients with cancer should be periodically assessed for VTE risk. Oncology professionals should educate patients about the signs and symptoms of VTE.

Symptomatic Toxicities Experienced During Anticancer Treatment: Agreement Between Patient & Physician Reporting in 3 Randomized Trials

abstract

Purpose Information about symptomatic toxicities of anticancer treatments is not based on direct report by patients, but rather on reports by clinicians in trials. Given the potential for under-reporting, our aim was to compare reporting by patients and physicians of six toxicities (anorexia, nausea, vomiting, constipation, diarrhea, and hair loss) within three randomized trials. 

Patients and Methods In one trial, elderly patients with breast cancer received adjuvant chemotherapy; in two trials, patients with advanced non–small-cell lung cancer received first-line treatment. Toxicity was prospectively collected by investigators (graded by National Cancer Institute Common Toxicity Criteria [version 2.0] or Common Terminology Criteria for Adverse Events [version 3]). At the end of each cycle, patients completed the European Organisation for Research and Treatment of Cancer quality-of-life questionnaires, including toxicity-related symptom items. Possible answers were “not at all,” “a little,” “quite a bit,” and “very much.” Analysis was limited to the first three cycles. For each toxicity, agreement between patients and physicians and under-reporting by physicians (ie, toxicity reported by patients but not reported by physicians) were calculated. 

Results Overall, 1,090 patients (2,482 cycles) were included. Agreement between patients and physicians was low for all toxicities. Toxicity rates reported by physicians were always lower than those reported by patients. For patients who reported toxicity (any severity), under-reporting by physicians ranged from 40.7% to 74.4%. Examining only patients who reported “very much” toxicity, under-reporting by physicians ranged from 13.0% to 50.0%. 

Conclusion Subjective toxicities are at high risk of under-reporting by physicians, even when prospectively collected within randomized trials. This strongly supports the incorporation of patient-reported outcomes into toxicity reporting in clinical trials.

Biomarker for PARP inhibitor responsiveness in ovarian cancer patients - video

video (2014)

 Prof Swisher talks to ecancertv at the 26th EORTC-NCI-AACR Symposium about data from a phase II trial, ARIEL2, which aims to identify patients with ovarian cancer likely to respond to rucaparib.

Population Distribution of Lifetime Risk of Ovarian Cancer in the United States

abstract

Background: 
In U.S. women, lifetime risk of ovarian cancer is 1.37%, but some women are at a substantially lower or higher risk than this average.

Methods:
We have characterized the distribution of lifetime risk in the general population.
Published data on the relative risks and their variances for five well-accepted risk and protective factors for ovarian cancer, oral contraceptive (OC) use, parity, tubal ligation, endometriosis and first degree family history of ovarian cancer in conjunction with a genetic risk score using genome-wide significant common, low penetrance variants were used. The joint distribution of these factors (i.e., risk/protective factor profiles) were derived using control data from four US population-based studies, providing a broad representation of women in the US.

Results: A total of 214 combinations of risk/protective factors were observed and the lifetime risk estimates ranged from 0.35% (95% CI 0.29-0.42) to 8.78% (95% CI 7.10-10.9). Among women with lifetime risk ranging from 4-9%, 73% had no family history of ovarian cancer; most of these women had a self-reported history of endometriosis.

Conclusions:
Profiles including the known modifiable protective factors of OC use and tubal ligation were associated with a lower lifetime risk of ovarian cancer. OC use and tubal ligation were essentially absent among the women at 4-9% lifetime risk.

Impact:
This work demonstrates that there are women in the general population who have a much higher than average lifetime risk of ovarian cancer. Preventive strategies are available. Should effective screening become available, higher than average risk women can be identified.

Epigenetic analysis of sporadic and Lynch-associated ovarian cancers reveals histology-specific patterns of DNA methylation

open access

 Abstract

Diagnosis and treatment of epithelial ovarian cancer is challenging due to the poor understanding of the pathogenesis of the disease. Our aim was to investigate epigenetic mechanisms in ovarian tumorigenesis and, especially, whether tumors with different histological subtypes or hereditary background (Lynch syndrome) exhibit differential susceptibility to epigenetic inactivation of growth regulatory genes. Gene candidates for epigenetic regulation were identified from the literature and by expression profiling of ovarian and endometrial cancer cell lines treated with demethylating agents. Thirteen genes were chosen for methylation-specific multiplex ligation-dependent probe amplification assays on 104 (85 sporadic and 19 Lynch syndrome-associated) ovarian carcinomas. Increased methylation (i.e., hypermethylation) of variable degree was characteristic of ovarian carcinomas relative to the corresponding normal tissues, and hypermethylation was consistently more prominent in non-serous than serous tumors for individual genes and gene sets investigated. Lynch syndrome-associated clear cell carcinomas showed the highest frequencies of hypermethylation. Among endometrioid ovarian carcinomas, lower levels of promoter methylation of RSK4, SPARC, and HOXA9 were significantly associated with higher tumor grade; thus, the methylation patterns showed a shift to the direction of high-grade serous tumors.

 

In conclusion, we provide evidence of a frequent epigenetic inactivation of RSK4, SPARC, PROM1, HOXA10, HOXA9, WT1-AS, SFRP2, SFRP5, OPCML, and MIR34B in the development of non-serous ovarian carcinomas of Lynch and sporadic origin, as compared to serous tumors. Our findings shed light on the role of epigenetic mechanisms in ovarian tumorigenesis and identify potential targets for translational applications.

• View full text
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• Supplemental

Improving Care and Support for Unpaid Caregivers in Ontario - Citizen Brief

This Citizen Brief was produced by the McMaster Health Forum to serve as the basis for discussions by a citizen panel about improving care and support for unpaid caregivers in Ontario.

The need to identify how to improve care and support for unpaid caregivers has attracted a lot of attention from governments, media and the public, in part because of the increasing number of people who are acting as unpaid caregivers. In 2012, it was estimated that 8.1 million Canadians provided care to a family member or friend with a long-term health condition (most commonly cancer) or aging-related needs. In Ontario, about 20% of the population serve as a caregivers to family members and provide the majority of care needed.

Much of the burden of continuing care falls on unpaid caregivers. In 2012, it was estimated that 8.1 million Canadians provided care to a family member or friend with a long-term health condition or aging-related needs.

A citizen panel is an innovative way to seek public input on high-priority issues. Each panel brings together 10-14 citizens from all walks of life. Panel members share their ideas and experiences on an issue, and learn from research evidence and from the views of others. The discussions of a citizen panel can reveal new understandings about an issue and spark insights about how it should be addressed.

This brief includes information on this topic, including what is known about:

• the underlying problem;
• three possible options to address the problem; and
• potential barriers and facilitators to implementing these options.

This brief does not contain recommendations, which would have required the authors to make judgments based on their personal values and preferences.

Technology and error-prevention strategies: Why are we still overlooking the IV room?

 open access
 

Variants of uncertain significance in BRCA : a harbinger of ethical and policy issues to come?

open access

2015 Ovarian Cancer National Conference –scholarships/agenda

OCNA

 Here's our other can't-miss news about the National Conference:

• We are now accepting scholarships to attend the National Conference. Our scholarship program allows patients and caregivers to learn about ovarian cancer and connect with others who share their experiences. A limited number of scholarships are available for travel, hotel and/or registration fees. Click here to apply for a 2015 scholarship. Please note: the last day to apply is Friday, April 3, 2015.

Have Insurers Found Way Around Obamacare 'Pre-Existing Conditions' Rule? (U.S.)

MedNews


WEDNESDAY Jan. 28, 2015, 2015 -- Some insurance companies may be using high-dollar pharmacy co-pays to flout the Affordable Care Act's (ACA) mandate against discrimination on the basis of pre-existing health problems, Harvard researchers claim.
These insurers may have structured their drug coverage to discourage people with HIV from enrolling in their plans through the health insurance marketplaces created by the ACA, sometimes called "Obamacare," the researchers contend in the Jan. 29 issue of the New England Journal of Medicine......

'... It's important for consumers to know that if they find themselves in plans like this, they should be reporting it to their state insurance commissioner, the HHS Office of Civil Rights, and their health insurance marketplace," she said.
More information
For more on the Affordable Care Act, visit the U.S. Department of Health and Human Services.

Coexistent ARID1A-PIK3CA mutations promote ovarian clear-cell tumorigenesis through pro-tumorigenic inflammatory cytokine signalling

abstract

Ovarian clear-cell carcinoma (OCCC) is an aggressive form of ovarian cancer with high ARID1A mutation rates. Here we present a mutant mouse model of OCCC. We find that ARID1A inactivation is not sufficient for tumour formation, but requires concurrent activation of the phosphoinositide 3-kinase catalytic subunit, PIK3CA. Remarkably, the mice develop highly penetrant tumours with OCCC-like histopathology, culminating in haemorrhagic ascites and a median survival period of 7.5 weeks. Therapeutic treatment with the pan-PI3K inhibitor, BKM120, prolongs mouse survival by inhibiting the tumour cell growth. Cross-species gene expression comparisons support a role for IL-6 inflammatory cytokine signalling in OCCC pathogenesis. We further show that ARID1A and PIK3CA mutations cooperate to promote tumour growth through sustained IL-6 overproduction. Our findings establish an epistatic relationship between SWI/SNF chromatin remodelling and PI3K pathway mutations in OCCC and demonstrate that these pathways converge on pro-tumorigenic cytokine signalling. We propose that ARID1A protects against inflammation-driven tumorigenesis.

Myriad Genetics Ending Patent Dispute on Breast Cancer Risk Testing

Media

Right patient, right drug, wrong dose? Cancer World

open access

Assessment of published models and prognostic variables in ovarian cancer at Mayo Clinic

Abstract

OBJECTIVES:

Epithelial ovarian cancer (EOC) is an aggressive disease in which first line therapy consists of a surgical staging/debulking procedure and platinum based chemotherapy. There is significant interest in clinically applicable, easy to use prognostic tools to estimate risk of recurrence and overall survival. In this study we used a large prospectively collected cohort of women with EOC to validate currently published models and assess prognostic variables.

METHODS:

Women with invasive ovarian, peritoneal, or fallopian tube cancer diagnosed between 2000-2011 and prospectively enrolled into the Mayo Clinic Ovarian Cancer registry were identified. Demographics and known prognostic markers as well as epidemiologic exposure variables were abstracted from the medical record and collected via questionnaire. Six previously published models of overall and recurrence-free survival were assessed for external validity. In addition, predictors of outcome were assessed in our dataset.

RESULTS:

Previously published models validated with a range of c-statistics (0.587-0.827), though application of models containing variables not part of routine practice were somewhat limited by missing data; utilization of all applicable models and comparison of results is suggested. Examination of prognostic variables identified only the presence of ascites and ASA score to be independent predictors of prognosis in our dataset, albeit with marginal gain in prognostic information, after accounting for stage and debulking.

CONCLUSIONS:

Existing prognostic models for newly diagnosed EOC showed acceptable calibration in our cohort for clinical application. However, modeling of prospective variables in our dataset reiterates that stage and debulking remain the most important predictors of prognosis in this setting.

Borderline epithelial tumors of the ovary: Experience of 55 patients.

abstract

 The objective of the present study was to evaluate the clinicopathological features and the survival time estimates in patients treated for borderline ovarian tumors (BOTs). A retrospective review of all patients treated for BOTs at the University of Bari (Bari, Italy) between 1991 and 2011 was performed. Data were obtained from hospital records and gynecological oncology charts. A total of 55 patients were identified. The median age was 40 years (range, 13-79 years). The majority of the patients (85.5%) exhibited International Federation of Obstetrics and Gynecology (FIGO) stage I disease and the remainder exhibited FIGO stage II/III (7.3% in each stage). Serous histology was found in 60.0% of the cases and an elevation of the cancer antigen-125 serum level occurred in 23.6% of the cases. All patients underwent surgery and 3.7% received chemotherapy. In total, 10.9% exhibited recurrence and the median survival rate was 39 months. The median survival time and the five-year survival rate were 42 months (range, 16-84 months) and 97%, respectively. Therefore, BOTs have an excellent prognosis. Conservative surgery should be considered for patients of reproductive age who desire preservation of fertility. A long-term follow-up is highly recommended for these tumors.

Lower Limb Lymphedema and Neurological Complications After Lymphadenectomy for Gynecological Cancer

abstract

Is There a Role for Oral or Intravenous Ascorbate (Vitamin C) in Treating Patients With Cancer?

abstract plus free full text

Conclusion. There is no high-quality evidence to suggest that
ascorbate supplementation in cancer patients either enhances
the antitumor effects of chemotherapy or reduces its toxicity.
Given the high financial and time costs to patients of this
treatment, high-quality placebo-controlled trials are needed.

 This Article

1. First Published Online January 19, 2015

   doi: 10.1634/theoncologist.2014-0381

   The Oncologist January 2015 theoncologist.2014-0381

1. » Abstract
2. Full Text (PDF)

An international ecological study of adult height in relation to cancer incidence for 24 anatomical sites

Abstract

Recalls, Market Withdrawals: J.J. Fuds, Inc. Issues Recall of Pet Food Because of Possible Health Risk

Recalls, Market Withdrawals

Causes of Diagnosis Errors & Prevention - CRICO risk Management

Blogger's Note: includes surgery and (selected) cancers; infographs

pdf

Causes of Diagnosis Errors & Prevention

CRICO Strategies, a division of the Risk Management Foundation of the Harvard Medical Foundation, just released the 2014 Annual Benchmarking Reporting: Malpractice Risks in the Diagnosis Process. This report analyzes more than 8,400 factors from 2,685 ambulatory diagnosis-related malpractice cases. The analysis helps to identify where and when diagnosis-related errors most commonly occur and what changes are needed to prevent them. This 20-page report is available on the CRICO Strategies website.

Malnutrition at Hospital Admission—Contributors and Effect on Length of Stay (Canada)

abstract

Background:
In hospitals, length of stay (LOS) is a priority but it may be prolonged by malnutrition. This study seeks to determine the contributors to malnutrition at admission and evaluate its effect on LOS.  

Materials and Methods:
This is a prospective cohort study conducted in 18 Canadian hospitals from July 2010 to February 2013 in patients ≥ 18 years admitted for ≥ 2 days. Excluded were those admitted directly to the intensive care unit; obstetric, psychiatry, or palliative wards; or medical day units. At admission, the main nutrition evaluation was subjective global assessment (SGA). Body mass index (BMI) and handgrip strength (HGS) were also performed to assess other aspects of nutrition. Additional information was collected from patients and charts review during hospitalization.  

Results:
One thousand fifteen patients were enrolled: based on SGA, 45% (95% confidence interval [CI], 42%–48%) were malnourished, and based on BMI, 32% (95% CI, 29%–35%) were obese. Independent contributors to malnutrition at admission were Charlson comorbidity index > 2, having 3 diagnostic categories, relying on adult children for grocery shopping, and living alone. The median (range) LOS was 6 (1–117) days. After controlling for demographic, socioeconomic, and disease-related factors and treatment, malnutrition at admission was independently associated with prolonged LOS (hazard ratio, 0.73; 95% CI, 0.62–0.86). Other nutrition-related factors associated with prolonged LOS were lower HGS at admission, receiving nutrition support, and food intake < 50%. Obesity was not a predictor.  

Conclusion: Malnutrition at admission is prevalent and associated with prolonged LOS. Complex disease and age-related social factors are contributors.

Will Cancer Society's Redo Be Its Undoing? (U.S.)

Medpage Today

"... "When I joined the Board funding for external research grants was 22% and when I left it was down to 10%,"...

Case Report: METASTASIS OF OVARIAN CANCER TO BREAST: THE IMPORTANCE OF PATHOLOGIC FEATURES IN THE DIAGNOSIS OF RECURRENCES

open access(pdf)


 .....We suggest that, in patients with history of ovarian cancer who present with axillary or breast mass, every effort should be made to have an accurate histological diagnosis since this has a great impact on treatment. It is critical to recognize histologic pattern and distinguish it from de novo ductal carcinoma in situ. Immunohistochemistry is essential when the diagnosis is still vague.

Cytologic features of ovarian granulosa cell tumors in pleural and ascitic fluids

abstract

Adult granulosa cell tumor (AGCT) is an uncommon neoplasm of the ovary with potential for aggressive behavior and late recurrence. The most important prognostic factor for AGCT is tumor stage. Thus, cytological assessment of pleural or ascitic fluids is crucial for initial staging and subsequent patient management. We report herein two cases of ovarian AGCT presenting with exfoliated tumor cells in pleural and ascitic fluid. The first case involved a 61-year-old woman who presented with stage Ic (a) AGCT. Seven years after initial diagnosis, pleural effusion and pleural dissemination were identified. The second case involved a 50-year-old woman who presented with stage IV AGCT with massive ascites and right pleural effusion. Fluid cytology from both cases showed cohesive or loose clusters of small uniform neoplastic cells with round-to-oval nuclei, coffee-bean-shaped nuclear grooves, small nucleoli, and scant cytoplasm. Call-Exner bodies were also observed in these cytologic specimens. In the differential diagnosis of small monomorphic tumor cells in pleural effusion or ascites, coffee-bean-shaped nuclear grooves and cell clusters forming Call-Exner bodies are diagnostic clues of AGCT. 

Relationship Between Surgical Oncologic Outcomes and Publically Reported Hospital Quality and Satisfaction Measures

abstract / editorial

 Abstract

 Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons

Background: Hospital-level measures of patient satisfaction and quality are now reported publically by the Centers for Medicare and Medicaid Services. There are limited metrics specific to cancer patients. We examined whether publically reported hospital satisfaction and quality data were associated with surgical oncologic outcomes. 

Methods: The Nationwide Inpatient Sample was utilized to identify patients with solid tumors who underwent surgical resection in 2009 and 2010. The hospitals were linked to Hospital Compare, which collects data on patient satisfaction, perioperative quality, and 30-day mortality for medical conditions (pneumonia, myocardial infarction [MI], and congestive heart failure [CHF]). The risk-adjusted hospital-level rates of morbidity and mortality were calculated for each hospital and the means compared between the highest and lowest performing hospital quartiles and reported as absolute reduction in risk (ARR), the difference in risk of the outcome between the two groups. All statistical tests were two-sided. 

Results: A total of 63197 patients treated at 448 hospitals were identified. For patients at high vs low performing hospitals based on Hospital Consumer Assessment of Healthcare Providers and Systems scores, the ARR in perioperative morbidity was 3.1% (blogger note: see abstract for stats -abbreviated for easy reading). Similarly, the ARR for mortality based on the same measure was -0.4% . High performance on perioperative quality measures resulted in an ARR of 0% to 2.2% for perioperative morbidity . Similarly, there was no statistically significant association between hospital-level mortality rates for MI , heart failure  or pneumonia  and complications for oncologic surgery patients. 

Conclusion: Currently available measures of patient satisfaction and quality are poor predictors of outcomes for cancer patients undergoing surgery. Specific metrics for long-term oncologic outcomes and quality are needed.

Related articles

Solicited Editorial:  
Patient Satisfaction, Outcomes, and the Need for Cancer-Specific Quality Metrics
 
• Extract 


In this issue of the Journal, Wright and colleagues highlight the relationship between patient satisfaction and thirty-day oncologic outcomes (1). The authors demonstrate that current publicly reported measures of quality and patient satisfaction are poorly correlated with thirty-day morbidity and mortality in patients undergoing solid tumor resections. The measures of patient satisfaction from Hospital Compare are for hospital-wide performance, not just oncology patients, so the findings are not particularly surprising. However, this study does highlight the need to: 1) examine whether patient experience and satisfaction really need to correlate with traditional measures of clinical quality (eg, outcomes), 2) discuss how patients seeking provider performance data are unable to access oncology-specific information from public reporting programs, and 3) discuss how cancer quality improvement efforts would benefit from both patient experience and traditional quality measures that are cancer specific.
An increasing emphasis has been placed on patient experience measures as they carry considerable weight in Centers for Medicare & Medicaid Services (CMS) pay-for-performance programs. A number of studies have sought to assess whether these patient experience measures are associated with outcomes. Some have demonstrated that hospitals with higher patient satisfaction …

Correspondence: Are we ready for conservative treatment in ovarian cancer?

Correspondence: open access

In conclusion, we think we are ready for fertility-sparing surgery in early epithelial ovarian cancer as an effective alternative to conventional radical surgery in younger women but just for selected cases where recurrence rate is very low such as FIGO stage IA/IB-G1/G2, and we need to be very careful with stages IC and G3 individualizing every case.

Original article: open access

Genetic polymorphisms and gene-dosage effect in ovarian cancer risk and response to paclitaxel/cisplatin chemotherapy (Poland)

open access

abstract

[brain tumors] Glioblastomas, astrocytomas and oligodendrogliomas linked to Lynch syndrome

abstract

 Glioblastomas, astrocytomas and oligodendrogliomas linked to Lynch syndrome

Background and purpose

Brain tumors represent a rare and relatively uncharacterized tumor type in Lynch syndrome.

Methods

The national Danish Hereditary Nonpolyposis Colorectal Cancer Register was utilized to estimate the cumulative life-time risk for brain tumors in Lynch syndrome, and the mismatch repair (MMR) status in all tumors available was evaluated.

Results

Primary brain tumors developed in 41/288 families at a median age of 41.5 (range 2–73) years. Biallelic MMR gene mutations were linked to brain tumor development in childhood. The risk of brain tumors was significantly higher (2.5%) in MSH2 gene mutation carriers compared to patients with mutations in MLH1 or MSH6. Glioblastomas predominated (56%), followed by astrocytomas (22%) and oligodendrogliomas (9%). MMR status was assessed in 10 tumors, eight of which showed MMR defects. None of these tumors showed immunohistochemical staining suggestive of the IDH1 R132H mutation.

Conclusion

In Lynch syndrome brain tumors occurred in 14% of the families with significantly higher risks for individuals with MSH2 gene mutations and development of childhood brain tumors in individuals with constitutional MMR defects.

Reporting and Grading Financial Toxicity (the Art of Oncology series)

open access

Table 1.

 

Proposed Financial Toxicity Grading Criteria

Grade	Description
1	Lifestyle modification (deferral of large purchases or reduced spending on vacation and leisure activities) because of medical expenditure
	Use of charity grants/fundraising/copayment program mechanisms to meet costs of care
2	Temporary loss of employment resulting from medical treatment
	Need to sell stocks/investments for medical expenditure
	Use of savings accounts, disability income, or retirement funds for medical expenditure
3	Need to mortgage/refinance home to pay medical bills
	Permanent loss of job as a result of medical treatment
	Current debts > household income
	Inability to pay for necessities such as food or utilities
4	Need to sell home to pay for medical bills
	Declaration of bankruptcy because of medical treatment
	Need to stop treatment because of financial burden
	Consideration of suicide because of financial burden of care

What We Really Talk About When We Talk About Food (the Art of Oncology series)

maple syrup

Genetic cancer ovary - (review) Clinical Ovarian & Other Gynecologic Cancer

open access

 Article Outline

1. Introduction
   1. Genetic abnormalities
   2. Pathology
   3. Molecular biology
   4. BRCA1 is implicated in multiple cellular functions based on its proteins interactions:
   5. PARP inhibition and BRCA mutation:
   6. Clinical picture
   7. Screening
2. Prevention
   1. Chemoprevention
   2. Genetic counselling
   3. Prognosis
   4. Management of genetic cancer ovary
   5. Recent advances
   6. Future Perspectives
3. Conclusion
4. Uncited reference

Exceptions to the Rule: Case Studies in the Prediction of Pathogenicity for Genetic Variants in Hereditary Cancer Genes

abstract

 Based on current consensus guidelines and standard practice, many genetic variants detected in clinical testing are classified as disease-causing based on their predicted impact on the normal expression or function of the gene in the absence of additional data. However, our laboratory has identified a subset of such variants in hereditary cancer genes for which compelling contradictory evidence emerged after the initial evaluation following the first observation of the variant. Three representative examples of variants in BRCA1, BRCA2 and MSH2 that are predicted to disrupt splicing, prematurely truncate the protein, or remove the start codon were evaluated for pathogenicity by analyzing clinical data with multiple classification algorithms. Available clinical data for all 3 variants contradicts the expected pathogenic classification. These variants illustrate potential pitfalls associated with standard approaches to variant classification as well as the challenges associated with monitoring data, updating classifications, and reporting potentially contradictory interpretations to the clinicians responsible for translating test outcomes to appropriate clinical action. It is important to address these challenges now as the model for clinical testing moves towards the use of large multi-gene panels and whole exome/genome analysis, which will dramatically increase the number of genetic variants identified.