Gynecologic cancer outcomes in the elderly poor: A population-based study

elderly poor

BACKGROUND

Adults aged ≥65 years who are dually enrolled in Medicare and Medicaid are an at-risk group in health care. However, to the best of the authors' knowledge, the outcomes of women with gynecologic cancers in this population are unknown.

METHODS

The current study was a population-based cohort study of North Carolina state cancer registry cases of uterine, ovarian, cervical, and vulvar/vaginal cancers (2003-2009), with linked enrollment in Medicare and state Medicaid. Outcomes of all-cause mortality and stage of disease at the time of diagnosis were analyzed as a function of enrollment status using multivariate analysis and survival curves.

RESULTS

Of 4522 women aged ≥65 years (3702 of whom were enrolled in Medicare [82%] and 820 of whom were dually enrolled [18%]), there were 2286 cases of uterine (51%), 1587 cases of ovarian (35%), 302 cases of cervical (7%), and 347 cases of vulvar/vaginal (8%) cancers.

High incidence of germline BRCA mutation in patients with ER low-positive/PR low-positive/HER-2 neu negative tumors

abstract

BACKGROUND

The 2015 National Comprehensive Cancer Network guidelines recommend that genetic counseling and germline BRCA mutation testing be offered to women under age 60 with triple-negative breast cancer (TNBC). As a result of the 2010 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines for breast cancer, patients with breast cancers that are estrogen receptor (ER) or progesterone receptor (PR) low-positive (1%-9% on immunohistochemistry) are no longer strictly considered to have TNBC and may not be referred for genetic counseling. However, the incidence of BRCA mutation in patients with hormone receptor (HR) low-positive breast cancers remains unknown, and current ASCO/CAP guidelines may result in undertesting for BRCA mutations.

A high frequency of BRCA mutations in young black women with breast cancer residing in Florida

Abstract
 

BACKGROUND

Black women are disproportionately affected with triple-negative breast cancer and have relatively poor survival. To the authors' knowledge, it is not known to what extent differences in the clinical presentation of breast cancer between non-Hispanic white women and black women can be accounted for by the presence of mutations in the BRCA1 and BRCA2 genes. The authors sought to evaluate the frequency of BRCA pathogenic variants in a population-based sample of young black women with breast cancer.

METHODS

Black women diagnosed with invasive breast cancer at age ≤50 years from 2009 to 2012 were recruited to the study through the Florida Cancer Registry. Participants underwent genetic counseling, completed a study questionnaire, and consented to release of their medical records. Saliva specimens were collected for BRCA sequencing and large rearrangement testing through multiplex ligation-dependent probe amplification.

RESULTS

A DNA sample was evaluated for 396 women, 49 of whom (12.4%) had a mutation in BRCA1 or BRCA2. Eight recurrent mutations accounted for 49% of all pathogenic variants.

CONCLUSIONS

To the authors' knowledge, the prevalence of BRCA mutations among the Florida-based sample of young black women with breast cancer in the current study exceeds that previously reported for non-Hispanic white women. It is appropriate to recommend BRCA testing in all young black women with invasive breast cancer. 

Editorial: Are beta-blockers on the therapeutic horizon for ovarian cancer treatment?

Abstract

 Widely used medications for other disease processes, such as beta-blockers used for the management of hypertension, may provide therapeutic potential in patients with cancer, perhaps by altering the tumor microenvironment. The article by Watkins et al in the current issue performed a comprehensive review of beta-blocker use in women with ovarian cancer, and identified nonselective beta-blockers associated with longer overall survival.

Clinical impact of selective and nonselective beta-blockers on survival in patients with ovarian cancer

abstract
 

BACKGROUND

Preclinical evidence has suggested that sustained adrenergic activation can promote ovarian cancer growth and metastasis. The authors examined the impact of beta-adrenergic blockade on the clinical outcome of women with epithelial ovarian, primary peritoneal, or fallopian tube cancers (collectively, epithelial ovarian cancer [EOC]).

METHODS

A multicenter review of 1425 women with histopathologically confirmed EOC was performed. Comparisons were made between patients with documented beta-blocker use during chemotherapy and those without beta-blocker use.

RESULTS

The median age of patients in the current study was 63 years (range, 21-93 years). The sample included 269 patients who received beta-blockers. Of those, 193 (71.7%) were receiving beta-1–adrenergic receptor selective agents, and the remaining patients were receiving nonselective beta antagonists. The primary indication for beta-blocker use was hypertension but also included arrhythmia and postmyocardial infarction management. For patients receiving any beta-blocker, the median overall survival (OS) was 47.8 months versus 42 months for nonusers (P =.04). The median OS based on beta-blocker receptor selectivity was 94.9 months for those receiving nonselective beta-blockers versus 38 months for those receiving beta-1–adrenergic receptor selective agents (P<.001). Hypertension was associated with decreased OS compared with no hypertension across all groups. However, even among patients with hypertension, a longer median OS was observed among users of a nonselective beta-blocker compared with nonusers (38.2 months vs 90 months; P<.001).

 CONCLUSIONS
Use of nonselective beta-blockers in patients with EOC was associated with longer OS. These findings may have implications for new therapeutic approaches

The characteristic ultrasound features of specific types of ovarian pathology (Review)

open access
  
Abstract

Characterizing ovarian masses enables patients with malignancy to be appropriately triaged for treatment by subspecialist gynecological oncologists, which has been shown to optimize care and improve survival. Furthermore, correctly classifying benign masses facilitates the selection of patients with ovarian pathology that may either not require intervention, or be suitable for minimal access surgery if intervention is required. However, predicting whether a mass is benign or malignant is not the only clinically relevant information that we need to know before deciding on appropriate treatment. Knowing the specific histology of a mass is becoming of increasing importance as management options become more tailored to the individual patient......

 1. Introduction

The characterization of ovarian masses and distinguishing between benign and malignant pathology is important both to decrease unnecessary anxiety and enable decisions regarding optimal treatment. Benign pathology may be best treated conservatively or in a general gynecology unit using a minimal access approach. Conversely, suspected malignant masses should be referred to specialized units for further management. Thus prior knowledge of the nature of ovarian masses is essential not only for the patient but in order to organize clinical services in terms of planning, costs and overall management (1).

Transvaginal ultrasonography (TVS) is the most commonly employed imaging modality for the assessment of adnexal masses, and a number of prediction models have been created to maximize its predictive capability. In many countries the risk of malignancy index (RMI) (2) which combines ultrasound features, serum CA125 levels and the menopausal status of the patient is still used to characterize ovarian pathology. However, more recently logistic regression models and simple rules created by the International Ovarian Tumor Analysis (IOTA) group have been shown to perform better than the RMI (3–7).......

Pazopanib in ovarian cancer, Expert Review of Anticancer Therapy

abstract

 "The majority of women with ovarian cancer present with advanced disease, and ultimately relapse following primary surgery and platinum-taxane chemotherapy. Despite recent advances in the development of targeted agents in ovarian cancer, survival rates remain poor. The promising activity of bevacizumab, a VEGF receptor inhibitor, has stimulated research on the use of additional anti-angiogenic agents in ovarian cancer. Pazopanib, an oral tyrosine kinase inhibitor, targets VEGF receptor-1, -2 and -3, platelet-derived growth factor receptor-α and -β and c-kit; resulting in the inhibition of angiogenesis and tumor proliferation. Early phase studies (clinical trials - pazopanib) have demonstrated promising efficacy and tolerability. To date, there has been one Phase III trial of pazopanib in ovarian cancer, demonstrating a progression-free survival benefit in women treated with maintenance pazopanib following primary surgery and systemic therapy. This article summarizes the preclinical and clinical data of pazopanib in ovarian cancer, highlighting future research options for this agent."

(2014) Updates on drug discovery in ovarian cancer

Full Text
2014  Gynecologic Oncology Research and Practice
 Review: Updates on drug discovery in ovarian cancer

Introduction

In 2010, we published on recent advances in drug discovery for ovarian cancer [1]. Since then, multiple drugs have either failed to advance into further development, have newly been developed, or have demonstrated activity in phase III trials. For example, with respect to bevacizumab, several positive phase III trials have supported the use of this drug in upfront and recurrent ovarian cancer cases yet FDA approval is pending. Another example includes a 940 patient, phase III AGO-OVAR16 study which proved advantageous in ovarian cancer treatment with pazopanib, increasing median progression-free survival (PFS) by about 5.6 months [2]. In addition, trabectedin was previously discussed and positive phase III activity was reported, improving PFS, and overall response rate in a 672 patient study [3]. Lastly, phase III results from the TRINOVA-1 trial of over 900 patients found that trebananib (AMG 386) increased PFS as well as reduced disease progression and death by 34% when combined with paclitaxel. Unfortunately, several of the drugs previously described have been found to be inactive, or with disappointing clinical outcomes. This review will thus highlight new drugs for ovarian cancer that have recently demonstrated positive phase II activity (Table  1). The ultimate goal with this type of drug development is to achieve prolonged remission and improved quality of life (QOL), for patients with recurrent ovarian cancer.

Table 1

Updates in ovarian cancer drug discovery demonstrating positive phase II activity.....

Adenocarcinoma of Mullerian origin: review of pathogenesis, molecular biology, and emerging treatment paradigms

 Note: changes in staging classifications (eg. stage 11C deleted; expanded sub-categories...)

Full Text

 Recent data regarding the genetics and histopathology of epithelial ovarian cancer (EOC) has improved our understanding of ovarian carcinogenesis. These results and current hypotheses indicate that epithelial ovarian, peritoneal, and tubal cancers are not distinct entities but represent a spectrum of disease that originates in the Mullerian compartment. Due to this new information, the FIGO staging classification for ovarian, tubal, and peritoneal cancers was revised (Table 1) [2]. Tubal and peritoneal cancers are now included in the ovarian cancer staging classification, and the primary site designated when possible [2,3]. This new staging exemplifies our current understanding of the relationship between these disease entities and challenges our previous classification of ovarian, peritoneal, and tubal cancers. We and others assert that this group of gynecologic cancers should be collectively designated as adenocarcinomas of Mullerian origin. In this review, we will focus on the incidence, classification, and origin of Mullerian adenocarcinomas. We will also review the molecular and pathologic profiling that support the concept of adenocarcinomas of Mullerian origin as a unified entity and will assist in diagnostic and treatment paradigms......

Table 1

Ovarian cancer staging (FIGO 2013 vs. FIGO 1988)

Review

Incidence

It is difficult to discern how many annual deaths occur due to adenocarcinomas of Mullerian origin. While EOC caused approximately 14,030 deaths in the United States in 2013 [4] and 151,905 deaths worldwide in 2012 [5], it is unclear exactly how many deaths were caused by peritoneal and tubal cancers. Peritoneal and tubal carcinomas have been considered rare malignancies and separate entities from ovarian carcinomas; thus, epidemiologic studies have proven difficult [6]. Tubal carcinomas account for only 0.14-1.8% of gynecologic malignancies [7,8]. In the United States, from 1995–2004, the age adjusted incidence rates for tubal and peritoneal carcinomas were 3.7 and 6.8 per million, respectively [6]. Newer theories indicate that the number of peritoneal and tubal cancers may be grossly underestimated.

Additionally, CUP (cancer of unknown primary) accounts for 3-5% of malignant epithelial cancers [9] and in 2012, there were an estimated 31,000 new cases of CUP in the United States [10]. Potentially 5% of CUP may originate in the female reproductive system based on data from post mortem autopsy studies [9,11]. It is important to recognize the adenocarcinoma of Mullerian origin subset of CUP when it occurs, because these cancers will typically have a more favorable prognosis and sensitivity to platinum-based chemotherapeutic regimens [12].....

 

Current classification

Epithelial ovarian cancer classification

  EOC classification has changed significantly over the past decade. The most recent proposed division of EOC includes two distinct histologic groups: type I and type II cancers. It should be noted that the type I and type II classification is generally used to broadly classify ovarian neoplasms for research purposes based on their unique clinical and molecular genetic features [13]. The classification was not meant to be used for clinical purposes. Type I tumors include low-grade serous and low-grade endometrioid cancers, as well as mucinous, clear cell, and transitional cell carcinomas......

 

Peritoneal cancer classification

Peritoneal carcinomas have been called multiple names including peritoneal papillary serous carcinoma, peritoneal mesothelioma, primary peritoneal carcinoma, and normal-sized ovary carcinoma syndrome. In 1993, the Gynecologic Oncology Group established specific guidelines for the diagnosis of peritoneal carcinoma....

'Basket study': Clinical trial design explores responses to drugs based on specific mutations in patients' tumors

'Basket study'

..... The findings illustrate the preliminary clinical efficacy of vemurafenib in multiple nonmelanoma BRAFV600-mutated cancers. Of the 122 trial participants, clinical activity was observed in various tumor types. Preliminary vemurafenib activity was observed in non-small cell lung cancer as well as Erdheim-Chester disease and Langherhans cell histiocytosis. Response rate and median progression-free survival in non-small cell lung cancer was 42 percent and 7.3 months, respectively. In Erdheim-Chester disease and Langherhans cell histiocytosis, response rate was 43 percent; despite median treatment duration of 5.9 months, no patients progressed during therapy. Anecdotal responses were seen in anaplastic pleomorphic xanthoastrocytoma, anaplastic thyroid cancer, cholangiocarcinoma, salivary duct cancer, ovarian cancer, clear cell sarcoma, and colorectal cancer (cetuximab combination only).....

The FDA blundered badly on the Addyi (female viagra) approval - FierceBiotech

Addyi approval 

Conquest Summer 2015 - Jenna Arnold is reducing risk while leaving menopause for later | MD Anderson Cancer Center

MD Anderson Cancer Center - ('Conquest' newsletter)

New procedure allows women who carry BRCA gene mutations to lower their chances of developing cancer by removing their fallopian tubes, but not their ovaries

..... “Dr. Nebgen is conducting a proof-of-concept study — a smaller-scale study that is confirming for us that women are interested in salpingectomy to reduce cancer risk and stave off menopause,” Lu says. “Now we’re ready to build on that initial research with larger studies that give us data on salpingectomy’s safety and effectiveness.”
Until then, Nebgen considers salpingectomy an option for women who say “absolutely no” to the recommended, more aggressive fallopian tube and ovary removal surgery.
“Salpingectomy is not yet the standard of care,” she says. “But it’s an evolving alternative.”

Efficacy of a brief manualized intervention Managing Cancer and Living Meaningfully (CALM) adapted to German cancer care settings: study protocol for a randomized controlled trial

study protocol - open access
  Efficacy of a brief manualized intervention Managing Cancer and Living Meaningfully (CALM) adapted to German cancer care settings: study protocol for a randomized controlled trial
 

Background

Worldwide, eight million people died from cancer in 2010 - an increase of 38 % over the last two decades [1]. Numerous studies have shown high levels of symptom burden and psychosocial distress associated with advanced cancer [2]–[6]. Psychological distress can range from normal adaptive emotions through to higher levels of severe and clinically significant symptoms that fulfill the standardized diagnostic criteria for adjustment disorder, anxiety disorders, or depression [7]. Studies demonstrate a total prevalence for any mental disorder of 32 % across all tumor settings and stages [8] and prevalence rates of 30–50 % for all mood disturbances including adjustment disorders and depression in palliative care settings [9], [10].....

 
Discussion

Our study will contribute important statistical evidence on whether CALM can reduce depression and existential distress in a German sample of advanced and highly distressed cancer patients.

Trial registration

ClinicalTrials.gov NCT02051660

 

Prospective study of the relationship between coffee and tea with colorectal cancer risk: The PLCO Cancer Screening Trial

open access
  
Background:

  

Coffee and tea are commonly consumed and carry potential anticancer components that could reduce the risk of colorectal cancer; however, their relationships with colorectal cancer risk remain inconsistent.

Conclusion:

  The findings of this study do not provide evidence to suggest that drinking coffee or tea is beneficial in protecting against colorectal cancer.

Coffee, tea, caffeine intake, and the risk of cancer in the PLCO cohort

nature.com 

 Background:

The association between coffee intake, tea intake and cancer has been extensively studied, but associations are not established for many cancers. Previous studies are not consistent on whether caffeine may be the source of possible associations between coffee and cancer risk.

Conclusions:

We observed a decreased risk of endometrial cancer for coffee intake, and a decreased risk of cancer overall with tea intake.

JAMA Network - 4 articles/editorials (breast cancer) Aug 20, 2015

JAMA Network 

 

Viewpoint | August 20, 2015 

Staging the Axilla in Early Breast Cancer: Will Imaging Replace Surgery?

Editorial

Rethinking the Standard for Ductal Carcinoma In Situ Treatment

Original Investigation 

Breast Cancer Mortality After a Diagnosis of Ductal Carcinoma In Situ

Editorial: Rethinking the Standard for Ductal Carcinoma In Situ Treatment; 

Docetaxel Alone or in Combination With a Therapeutic Cancer Vaccine (PANVAC) in Patients With Metastatic Breast Cancer: A Randomized Clinical Trial

Study raises alarm about over-treating early stage breast cancer

 The Globe and Mail (media including Narod's comments) August 20, 2015

..." “Everybody in the world is saying, ‘I don’t need to treat my DCIS,’” he (Narod)  said. “Nothing could be further from the truth. You must, absolutely, completely remove the DCIS and additional treatment is not necessary.”

Original Investigation | August 20, 2015

Breast Cancer Mortality After a Diagnosis of Ductal Carcinoma In Situ FREE

 Editorial | August 20, 2015

Rethinking the Standard for Ductal Carcinoma In Situ Treatment FREE

MCI professor (gyn/oncology) seeks to learn why cancer rates are higher in minority patients

Media

 With MCI since 2007, Dr. Rodney P. Rocconi has been appointed professor of Interdisciplinary Clinical Oncology and chief of Gynecologic Oncology Service at the University of South Alabama Mitchell Cancer Institute, according to officials......

Retrieving Clinical Evidence: A Comparison of PubMed and Google Scholar

 open access: Journal of Medical Internet Research
 Retrieving Clinical Evidence: A Comparison of PubMed and Google Scholar for Quick Clinical Searches

Background: Physicians frequently search PubMed for information to guide patient care. More recently, Google Scholar has gained popularity as another freely accessible bibliographic database.

Results: Compared with PubMed, the average search in Google Scholar retrieved twice as many relevant articles (PubMed: 11%; Google Scholar: 22%; P<.001). Precision was similar in both databases (PubMed: 6%; Google Scholar: 8%; P=.07). Google Scholar provided significantly greater access to free full-text publications (PubMed: 5%; Google Scholar: 14%; P<.001).

Conclusions: For quick clinical searches, Google Scholar returns twice as many relevant articles as PubMed and provides greater access to free full-text articles.

Early salpingectomy (TUbectomy) with delayed oophorectomy to improve QOL as alternative for risk-reducing salpingo-oophorectomy in BRCA 1/2 mutation carriers

 Full text - Study Protocol
Early salpingectomy (TUbectomy) with delayed oophorectomy to improve quality of life as alternative for risk-reducing salpingo-oophorectomy in BRCA1/2 mutation carriers (TUBA study): a prospective non-randomised multicentre study
 

Background

Risk-reducing salpingo-oophorectomy (RRSO) around the age of 40 is currently recommended to BRCA1/2 mutation carriers. This procedure decreases the elevated ovarian cancer risk by 80–96 % but it initiates premature menopause as well. The latter is associated with short-term and long-term morbidity, potentially affecting quality of life (QoL). Based on recent insights into the Fallopian tube as possible site of origin of serous ovarian carcinomas, an alternative preventive strategy has been put forward: early risk-reducing salpingectomy (RRS) and delayed oophorectomy (RRO). However, efficacy and safety of this alternative strategy have to be investigated. 

.......Although a randomised controlled trial would be the preferred study design, an earlier published feasibility study among healthcare professionals and germline BRCA1/2 mutation carriers showed that randomisation would be an insurmountable barrier for participation in a clinical study [51]. These women want to decide themselves on their risk-reducing strategy and it is therefore unlikely that they will participate in a randomised controlled trial. Taken this into account, a prospective non-randomised design seems the most appropriate, letting women the opportunity to decide for themselves......

Discussion

In this study protocol, we describe a prospective non-randomised multicentre trial in premenopausal BRCA mutation carriers. We compare the standard strategy to reduce ovarian cancer risk, i.e. RRSO at recommended age of 35–40 in BRCA1 and at recommended age of 40–45 in BRCA2 mutation carriers, with an innovative risk-reducing strategy. In this innovative strategy, early RRS is performed upon completion of childbearing and subsequent RRO is delayed for five years compared to the currently recommended age for the standard strategy. The primary outcome measure is menopause-related QoL. Secondary outcome measures include safety (cancer incidence and surgical complications), histopathological findings of surgery specimens, cardiovascular risk factors and cost-effectiveness.

Currently, there are two other ongoing studies investigating different aspects of salpingectomy in germline BRCA mutation carriers.

Intratumoral interleukin-6 predicts ascites formation in patients with epithelial ovarian cancer: A potential tool for close monitoring

Full text 

 Background

The implication of IL-6 in the pathogenesis of epithelial ovarian cancer (EOC) is well documented. Accordingly, the clinicopathological significance of this cytokine in patients’ ascites fluid or serum has largely been investigated. Since the main source of IL-6 secreted into the biological fluids is the tumor tissue, this study was designed to investigate the status and possible clinical relevance of the IL-6 expression in an array of EOC tissue specimens. 

  

Table 1

Clinicopathological characteristics of the participants
 
Results

An upregulation of IL-6 expression was observed in EOC tissues as compared with the normal samples (p < 0.0001). As regards the clinical relevance, IL-6 failed to predict OS, DFS and response to the platinum-based chemotherapy in EOC patients. In multivariate analysis, however, IL-6 was identified as an independent predictive factor for the development of post-treatment ascites (p:0.033).

Conclusions

Having the capability to predict the ascites formation, IL-6 might serve as a biomarker and a useful tool in EOC for monitoring purposes. IL-6 targeting for the prevention of the ascites development is a potential avenue for further investigation. 

 

Graph (G) depicts maximum and minimum expression scores of IL-6 in different subgroups of EOC. HGS: high grade serous; LGS: low grade serous; M: mucinous; HGE: high grade endometrioid; LGE: low grade endometrioid; C: clear cell; O: others. Magnification = 40x

Conclusions

Here, we report the upregulation of IL-6 in EOC, with predictive value for development of ascites following the platinum-based treatment. In keeping with results from previous studies, our findings highlight the role of this cytokine in EOC patients which needs to be further explored in future research.