(U.S.) Setting a National Agenda for Surgical Disparities Research: Recommendations

open access

Special Communication | March 16, 2016

Setting a National Agenda for Surgical Disparities ResearchRecommendations From the National Institutes of Health and American College of Surgeons Summit

References:  (ovarian cancer quick search)

29.

Bristow  RE, Powell  MA, Al-Hammadi  N,  et al.  Disparities in ovarian cancer care quality and survival according to race and socioeconomic status. J Natl Cancer Inst. 2013;105(11):823-832.
PubMed   |  Link to Article

 

56.

Liu  FW, Randall  LM, Tewari  KS, Bristow  RE.  Racial disparities and patterns of ovarian cancer surgical care in California. Gynecol Oncol. 2014;132(1):221-226.
PubMed   |  Link to Article

 

70.

Boyd  LR, Novetsky  AP, Curtin  JP.  Ovarian cancer care for the underserved: are surgical patterns of care different in a public hospital setting? Cancer. 2011;117(4):777-783.

PubMed   |  Link to Article

 

72.

Bristow  RE, Chang  J, Ziogas  A, Randall  LM, Anton-Culver  H.  High-volume ovarian cancer care: survival impact and disparities in access for advanced-stage disease. Gynecol Oncol. 2014;132(2):403-410.
PubMed   |  Link to Article

 

 

 

New and Updated Language Translations of NCCN Guidelines for Ovarian Cancer Now Available

New and Updated Language Translations of NCCN Guidelines for Ovarian Cancer Now Available

By Jorge Bacigalupo, Global Business Development Specialist, NCCN
The National Comprehensive Cancer Network^® (NCCN^®) recently posted translations of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Ovarian Cancer in the following languages:

• Brazilian Portuguese
• Chinese
• French
• Korean
• Latin America Spanish
• Polish

The NCCN Guidelines^® continue to progress as the global standard for clinical practice and policy.

Front-line IP versus IV chemotherapy in stage III-IV epithelial ovarian, tubal, and peritoneal cancer with minimal residual disease: a competing risk analysis

open access
Front-line intraperitoneal versus intravenous chemotherapy in stage III-IV epithelial ovarian, tubal, and peritoneal cancer with minimal residual disease: a competing risk analysis 

 A total of 1263 patients were recruited as the initial cohort.

...Most published studies for ovarian cancer use the time to some disease events as their primary outcome and hence, statistical methods developed for survival data are usually applied. Established methods for estimating and modelling these include the Kaplan–Meier estimator of the survival function and the Cox proportional hazards model for the hazard function [7, 8] An important assumption of these established survival analytical methods is that censoring is ‘independent’ [9]. However, in some cases, several causes of failure are possible but the occurrence of one event precludes the occurrence of the other events (i.e., when failures are different causes of death, only the first one can be observed). This situation is known as competing risks. In a competing risk situation, standard techniques for survival analysis may lead to incorrect and biased results [10, 11]. In usual condition, ovarian cancer often presents a protracted disease course, and it is not uncommon to see a patient dies of other causes (e.g., heart failure and stroke), which precludes the occurrence of cancer-specific death.

In the current work, we conducted a competing risk analysis to investigate the therapeutic effects of intraperitoneal chemotherapy on stage III-IV epithelial ovarian, tubal, and peritoneal cancer with minimal residual disease using an administrative health care database constructed in a single tertiary care institution (Taipei).....

.... Traditionally, when predict the unadjusted probability of a certain event of interest to occur, one can use the Kaplan–Meier (KM) method. However, in the presence of competing risks, using the KM method is problematic. This method can handle only one single event at one time, and all other events are treated as censored observations. Further, the complement of the KM estimate (1 − KM) is interpreted as the cumulative probability of the event of interest in a hypothetical world where no subject would experience the competing event. This kind of interpretation is not realistic in clinical practice [28]......

 Several limitations merit consideration in the current work.

Conclusions

In conclusion, results from this competing risk analysis provide supportive evidence for previous published randomized trials that intraperitoneal chemotherapy outperforms intravenous chemotherapy. We propose that implementation of competing risk analysis should be highly considered for the investigation of ovarian cancer patients who have medium to long-term follow-up period.

Surgical management of cardiophrenic lymph nodes in patients with advanced ovarian cancer

abstract
 

Highlights

•

Importance of complete resection in primary ovarian cancer

•

Excision of suspicious cardiophrenic lymph nodes via a transdiaphragmatic approach

•

Feasibility, management and complications of resection

---

Abstract

Objective

Debulking surgery for advanced ovarian cancer does not routinely include opening of the thorax. Even systematic lymphadenectomy does not commonly extend to lymph nodes above the diaphragm. We evaluated the outcome of systematic resection of suspicious cardiophrenic lymph nodes detected on preoperative CT-scan in patients with advanced epithelial ovarian cancer (EOC).

Prevalence and factors associated with cognitive deficit in women with gynecologic malignancies

abstract

 Highlights

•

60% of women with gynecologic cancers have decreased cognition by MoCa screening.

•

Age, race, education, cancer site and pain were associated with decreased cognition.

•

Decreased cognition was associated with pain > 5, but not with opioid use.

---

Abstract

Objective

Cognitive impairment has implications in counseling, treatment, and survivorship for women with gynecologic malignancies. The purpose of our study was to evaluate the prevalence and risk factors associated with cognition in women with gynecologic malignancies.

Methods

After Institutional Review Board approval, 165 women at an urban ambulatory gynecologic oncology facility were queried using a Montreal Cognitive Assessment (MoCA), Wong–Baker pain scale, neuropathy scale, Patient Health Questionnaire 9 (PHQ-9) Depression Scale, and Generalized Anxiety Disorder Scale (GAD 7). Univariate and multivariate analyses were utilized to evaluate the association of cognitive deficit with age, education, race/ethnicity, disease site, stage, treatment, pain, neuropathy, anxiety, and depression.

Results

The mean MoCA score for the entire cohort was 24.1 (range 13–30.) 24% of patients had MoCA scores less than 22. Low scores (< 22) were associated with older age, non-white race/ethnicity, lower education level, uterine and vulvar cancers, and pain ≥ 5 (p < 0.05). There was a trend toward lower cognition scores for women treated with both chemotherapy and radiation (p = 0.10). While clinically significant pain was associated with low cognition, there was no association with use of opioid pain medication and low cognition scores.

Conclusions

There was a high prevalence of cognitive deficit in women with gynecologic malignancies. The association of low cognition with report of clinically significant pain, but not with use of opioid pain medications, should be further explored. Research is needed to evaluate the impact of cognitive deficits on treatment adherence and outcomes for women with gynecologic malignancies.

PD-L1 expression is associated with tumor-infiltrating T cells and favorable prognosis in high-grade serous ovarian cancer

abstract

 Highlights

•

Expression of PD-L1 in ovarian cancer was revaluated using modern antibody reagents

•

PD-L1 expression positively correlated with tumor infiltrating lymphocytes

•

PD-L1 expression was a favorable prognostic feature of high grade serous cancer

---

Abstract

Objective

As a negative regulator of T cells, Programmed Death Ligand 1 (PD-L1) is both an indicator and inhibitor of anti-tumor immune responses, which has led to confusion about its prognostic significance. We investigated the primary source of PD-L1 expression in epithelial ovarian cancer and its relationship to tumor-infiltrating lymphocytes (TIL) and associated gene products.

Methods

Tissue microarrays containing high-grade serous carcinomas (HGSC) and endometrioid, clear cell and mucinous ovarian cancers from optimally debulked patients were assessed by immunohistochemistry for expression of PD-L1 and other markers (CD68, CD3, CD8, PD-1, CD103, FoxP3 and CD25). The Cancer Genome Atlas was interrogated for associations between PD-L1 expression and immune-related transcriptional and genomic features of HGSC.

Conclusions

PD-L1 is primarily expressed by macrophages in ovarian cancer and is strongly associated with both cytolytic and regulatory TIL subsets, resulting in a net positive association with survival. Tumors containing PD-L1⁺ macrophages appear caught in an immunological stalemate that may require multi-pronged immunotherapy to alleviate.

Evaluation of satisfaction with work–life balance among U.S. Gynecologic Oncology fellows: A cross-sectional study

open access

Highlights

•

Most gynecologic oncology fellows are not satisfied with their work–life balance.

•

Working 80 h per week or more predicts dissatisfaction with work–life balance.

•

Satisfied fellows plan to work 3.5 years longer than those who are not satisfied.

 Unlike those other specialties, gynecologic oncology has a high proportion of female physicians and is sensitive to factors that differentially affect careers based on gender (Wallace et al., 2010 and Gordinier et al., 2000). Among medical oncologists, dissatisfaction with WLB (work life balance)  is associated with plans to reduce clinical hours and leave current medical practice (Shanafelt et al., 2014a). The purpose of this study was to characterize the current state of satisfaction with work–life balance among gynecologic oncology fellows and the impact of that balance on future career plans.

Bevacizumab helped resolve pericardial and pleural effusion that was associated with malignant ovarian clear cell carcinoma

open access

 Highlights

•

An ovarian clear cell carcinoma patient showed malignant pericardial and pleural effusion.

•

She subsequently experienced pulmonary embolism due to cancer progression.

•

Pericardial and pleural effusion were successfully treated using bevacizumab.

Case report

A 52-year-old nulliparous woman initially visited our hospital with an ovarian tumor of 19 cm in diameter in 2010. After primary debulking surgery, she was diagnosed with stage IC ovarian clear cell carcinoma with positive cytology of ascites and the rupture of the left ovarian tumor during surgery. She underwent 6 cycles of adjuvant chemotherapy with paclitaxel and carboplatin. Three years later, she developed multiple lung metastases (maximum diameter: 20 mm) and subsequently underwent 6 cycles of paclitaxel and carboplatin, which resulted in complete remission. However, she developed malignant ascites with lung metastases (maximum diameter: 10 mm) and deep vein thrombosis after 14 months.....

Review: Medical Marijuana Use in Oncology

JAMA Network open access

ABSTRACT | INTRODUCTION | HISTORY AND LEGAL STATUS | MECHANISM OF ACTION | CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING | CANCER-ASSOCIATED PAIN | CANNABIS AS AN ANTITUMOR AGENT | SAFETY PROFILE OF CANNABIS | CONCLUSIONS | ARTICLE INFORMATION | REFERENCES

open access (2) Secondary Infections Intensive Care

Editorial | March 15, 2016  FREE

Immunosuppression and Secondary Infection in Sepsis: Part, Not All, of the Story

PDF

Derek C. Angus, MD, MPH; Steven Opal, MD

Original Investigation | March 15, 2016  FREE

 

Incidence, Risk Factors, and Attributable Mortality of Secondary Infections in the Intensive Care Unit After Admission for Sepsis

PDF

Lonneke A. van Vught, MD; Peter M. C. Klein Klouwenberg, MD, PharmD, PhD; Cristian Spitoni, PhD; Brendon P. Scicluna, PhD; Maryse A. Wiewel, MD; Janneke Horn, MD, PhD; Marcus J. Schultz, MD, PhD; Peter Nürnberg, PhD; Marc J. M. Bonten, MD, PhD; Olaf L. Cremer, MD, PhD; Tom van der Poll, MD, PhD; for the MARS Consortium

Includes: Supplemental Content

Editorial: Immunosuppression and Secondary Infection in Sepsis; Derek C. Angus, MD, MPH; Steven Opal, MD

Managing the Risks of Concurrent Surgeries

JAMA Network open access

.... Overlapping or concurrent operations involve scheduling substantive portions of 2 or more surgeries to occur during the same time. In these overlapping operations, delegation of responsibility to trainees and assistants is necessary. Particularly at teaching hospitals, concurrent surgeries are not uncommon, but the practice may not be well understood by patients. Although overlapping operations can often be managed responsibly, 2 problems require attention. First, what are the boundaries of safe practice (and who should set them)? Second, how should surgeons communicate with patients about these practices?....

Physician-assisted death: we want your feedback - Sunnybrook Hospital - patient/community engagement

background including public comments
 

IOM Committee Recommends Oversight, Common Evidentiary Standards for Biomarker Tests for Molecularly-targeted Therapies

Cancer Therapy Advisor


References

1. (open access) Committee on Policy Issues in the Clinical Development and Use of Biomarkers for Molecularly Targeted Therapies; Board on Health Care Services; Institute of Medicine; The National Academies of Sciences, Engineering, and Medicine. Graig LA, Phillips JK, Moses HL, eds. Biomarker tests for molecularly targeted therapies: key to unlocking precision medicine. Washington (DC): National Academies Press (US); 2016. 

 PREPUBLICATION DRAFT (229 pages)

This title is currently only available in Bookshelf as a prepublication draft version in PDF format (9.2M). The final version is forthcoming.

2. Mapes D. This is the future of oncology. Fred Hutch News Service. http://www.fredhutch.org/en/news/center-news/2016/03/precision-medicine-report-lays-plans-for-improved-patient-care.html. Published March 4, 2016. Accessed March 17, 2016.

 Research is beginning to assess adherence rates, and the impact
on survival and quality of life associated with adherence to certain guidelines in clinical conditions such as breast (Cloud et al., 2015; Henry et al., 2014) and ovarian cancers (Lee et al., 2015). However, while inclusion in a CPG may suggest a biomarker test and corresponding
targeted therapy have clinical utility when used together, formal assessment of clinical utility is beyond the scope of CPG development.

REG4 Is Highly Expressed in Mucinous Ovarian Cancer: A Potential Novel Serum Biomarker (non serous)

open access

 Abstract
Preoperative diagnostics of ovarian neoplasms rely on ultrasound imaging and the serum biomarkers CA125 and HE4. However, these markers may be elevated in non-neoplastic conditions and may fail to identify most non-serous epithelial cancer subtypes. The objective of this study was to identify histotype-specific serum biomarkers for mucinous ovarian cancer. The candidate genes with mucinous histotype specific expression profile were identified from publicly available gene-expression databases and further in silico data mining was performed utilizing the MediSapiens database. Candidate biomarker validation was done using qRT-PCR, western blotting and immunohistochemical staining of tumor tissue microarrays. The expression level of the candidate gene in serum was compared to the serum CA125 and HE4 levels in a patient cohort of prospectively collected advanced ovarian cancer. Database searches identified REG4 as a potential biomarker with specificity for the mucinous ovarian cancer subtype. The specific expression within epithelial ovarian tumors was further confirmed by mRNA analysis. Immunohistochemical staining of ovarian tumor tissue arrays showed distinctive cytoplasmic expression pattern only in mucinous carcinomas and suggested differential expression between benign and malignant mucinous neoplasms. Finally, an ELISA based serum biomarker assay demonstrated increased expression only in patients with mucinous ovarian cancer. This study identifies REG4 as a potential serum biomarker for histotype-specific detection of mucinous ovarian cancer and suggests serum REG4 measurement as a non-invasive diagnostic tool for postoperative follow-up of patients with mucinous ovarian cancer.

Ovarian cancer: Weekly or 3-weekly paclitaxel are equally effective

Nature Reviews Clinical Oncology (req's $$$ to access)

 Patients with ovarian cancer typically receive paclitaxel plus carboplatin, and many are also treated with bevacizumab. Now, data from a randomized phase III trial comparing 3-weekly paclitaxel with a lower, weekly dose reveal no significant differences in progression-free survival (PFS) among newly-diagnosed patients with previously untreated ovarian cancer on either…

 Read the full article

• Subscribe to Nature Reviews Clinical Oncology for full access: $199

  Subscribe Purchase article full text and PDF: $8

article index - special edition: Original Cancer Costing Research Using Canadian Data

open access (req's registration/free)
 

Vol 23 (2016)

Table of Contents

Editorial(s)

Original Canadian cancer costing research for cancer control sustainability, quality, and value	PDF HTML
H. Bryant	S5

Importance of cost estimates and cost studies	PDF HTML
N. Mittmann, C. de Oliveira	S6

Original Article(s)

Home-Based Primary Care Interventions - home-based-care-report

AHRQ CER 164 open access

 Conclusions. Current research evidence is generally positive, providing moderate-strength evidence that HBPC (home based primary care) reduces use of inpatient care and providing low-strength evidence about its impact on use of other health services, costs, and patient and caregiver experience. Future research should focus on the content and organizational context of HBPC interventions so that experiences can be replicated or improved on by others. Additional research is also needed about which patients benefit most from HBPC and how HBPC can best be used in the continuum of care.

Why some tumors withstand treatment -- kinase inhibitors

ScienceDaily
 
Bypass system
Kinase inhibitors, frequently used against breast, ovarian, and other cancers, work by disrupting cell signaling pathways that stimulate cells to grow, proliferate, or become invasive. Doctors usually prescribe them based on whether a patient's tumor is overexpressing a cancer-driving protein such as epithelial growth factor receptor (EGFR).
However, these drugs can fail even in tumors where they should work. About half of these failures are caused by genetic mutations that allow cancer cells to evade the drug's actions, but the rest are unexplained, Lauffenburger says.
Based on their previous studies of endometriosis (when uterine tissue grows into surrounding organs), Lauffenburger and his colleagues suspected there could be a backup pathway helping cancer cells to sidestep the effects of kinase inhibitors. In those studies, the researchers found that invasive endometrial cells become "addicted" to a certain growth signal, and that this pathway actually shuts off other growth pathways. Drugs that shut down the primary pathway can have the unintended effect of activating those backup systems.
The MIT team wondered if the same thing might be happening in cancer cells......

"Evidence-based medicine has been hijacked:" A confession from John Ioannidis (interview)

open access
 

Tracking retractions as a window into the scientific process

“Evidence-based medicine has been hijacked:” A confession from John Ioannidis

John Ioannidis is perhaps best known for a 2005 paper “Why Most Published Research Findings Are False.” One of the most highly cited researchers in the world, Ioannidis, a professor at Stanford, has built a career in the field of meta-research. Earlier this month, he published a heartfelt and provocative essay in the the Journal of Clinical Epidemiology titled “Evidence-Based Medicine Has Been Hijacked: A Report to David Sackett.” In it, he carries on a conversation begun in 2004 with Sackett, who died last May and was widely considered the father of evidence-based medicine. We asked Ioannidis to expand on his comments in the essay, including why he believes he is a “failure.”
Retraction Watch: You write that as evidence-based medicine “became more influential, it was also hijacked to serve agendas different from what it originally aimed for.” Can you elaborate?
John Ioannidis: As I describe in the paper, “evidence-based medicine” has become a very common term that is misused and abused by eminence-based experts and conflicted stakeholders who want to support their views and their products, without caring much about the integrity, transparency, and unbiasedness of science.
RW: You also write that evidence-based medicine “still remains an unmet goal, worthy to be attained.” Can you explain further?
JI: The commentary that I wrote gives a personal confession perspective on whether evidence-based medicine currently fulfills the wonderful definition that David Sackett came up with: “integrating individual clinical expertise with the best external evidence”. This is a goal that is clearly worthy to be attained, but, in my view, I don’t see that this has happened yet. Each of us may ponder whether the goal has been attained. I suspect that many/most will agree that we still have a lot of work to do.
RW: You describe yourself as a “failure.” What do you mean?
JI: Well, I still know next to nothing, even though I am always struggling to obtain more solid evidence and even though I always want to learn more. If you add what are probably over a thousand rejections (of papers, grant proposals, nominations, and other sorrowful academic paraphernalia) during my career to-date, I think I can qualify for a solid failure. Nevertheless, I still greatly enjoy my work in science and in evidence-based medicine..

Adherence of Primary Care Physicians to Evidence-Based Recommendations to Reduce Ovarian Cancer Mortality (U.S.)

Abstract

Ovarian cancer is the deadliest gynecologic cancer. Receipt of treatment from a gynecologic oncologist is an evidence-based recommendation to reduce mortality from the disease. We examined knowledge and application of this evidence-based recommendation in primary care physicians as part of CDC gynecologic cancer awareness campaign efforts and discussed results in the context of CDC National Comprehensive Cancer Control Program (NCCCP). We analyzed primary care physician responses to questions about how often they refer patients diagnosed with ovarian cancer to gynecologic oncologists, and reasons for lack of referral. We also analyzed these physicians' knowledge of tests to help determine whether a gynecologic oncologist is needed for a planned surgery. The survey response rate was 52.2%. A total of 84% of primary care physicians (87% of family/general practitioners, 81% of internists and obstetrician/gynecologists) said they always referred patients to gynecologic oncologists for treatment. Common reasons for not always referring were patient preference or lack of gynecologic oncologists in the practice area. A total of 23% of primary care physicians had heard of the OVA1 test, which helps to determine whether gynecologic oncologist referral is needed. Although referral rates reported here are high, it is not clear whether ovarian cancer patients are actually seeing gynecologic oncologists for care. The NCCCP is undertaking several efforts to assist with this, including education of the recommendation among women and providers and assistance with treatment summaries and patient navigation toward appropriate treatment. Expansion of these efforts to all populations may help improve adherence to recommendations and reduce ovarian cancer mortality.

JAMA articles March 15th: Prescribing Opiods - Editorials/Communications

March 15, 2016 
 

Editorial

The CDC Guideline on Opioid Prescribing: Rising to the Challenge  

Yngvild Olsen, MD, MPH

Zero Pain Is Not the Goal  

Thomas H. Lee, MD, MSc

Special Communication

CDC Guideline for Prescribing Opioids for Chronic Pain—United States, 2016  

Deborah Dowell, MD, MPH; Tamara M. Haegerich, PhD; Roger Chou, MD

Opioids Prescribed After Low-Risk Surgical Procedures in the United States, 2004-2012  

Hannah Wunsch, MD, MSc; Duminda N. Wijeysundera, MD, PhD; Molly A. Passarella, MS; et al

JAMA Patient Page

Opioids for Chronic Pain  

LeShaundra Cordier Scott, MPH, CHES; Sarah Lewis, MPH, CHES

19 Common Side Effects of Chemotherapy (interactive graphic)

(click here) interactive graphic

Chemotherapy drugs are powerful enough to kill rapidly growing cancer cells, but they also can harm perfectly healthy cells, causing side effects throughout the body.

read more.

2016 Mar 15th: The State of Cancer Care in America, 2016 ASCO (note the # of oncologists/locations)

open access

This year’s report focuses on three areas that affect the complexity of cancer and its treatment: (1) cancer screening, (2) implementing precision medicine treatments, and (3) the aging of the US population.

 Distribution of oncologists represented by the ASCO Census, 2015

 

Lynch Syndrome Screening in the Gynecologic Tract: Current State of the Art

abstract

 Lynch syndrome underlies approximately 5% of endometrial cancers and ∼1% of ovarian cancers. Gynecologic malignancies are often the presenting cancer in these patients. Therefore, there is considerable benefit to identifying these patients and enrolling them and affected family members in surveillance programs for secondary malignancies. The molecular basis for Lynch syndrome is a defect in the DNA mismatch repair (MMR) system. Tumors can be screened for these defects using immunohistochemistry to identify loss of MMR proteins or by enlisting polymerase chain reaction to identify the microsatellite instability that attends dysfunctional MMR. However, diagnostic confirmation of Lynch syndrome requires germline mutational testing. The algorithm for screening endometrial carcinomas for Lynch syndrome remains a subject of debate, with some studies supporting universal screening and others proposing a hybrid approach informed by clinicopathologic features. This review discusses the rationales and relative merits of current Lynch syndrome-screening approaches for endometrial and ovarian cancers and provides pathologists with an informed approach to Lynch syndrome testing in gynecologic cancers. It also addresses the clinical difficulties presented by cases with discordant screening and germline results (Lynch-like cancers) and emphasizes the critical role of strong communication with clinician and genetic counseling colleagues to ensure that the significance of a positive screening test is appropriately conveyed to patients. Finally, it discusses the need for more nuanced cost-effective analyses and the potential role for next-generation sequencing panels in future screening efforts.

(UTUC) Upper Tract Urothelial Carcinoma: Special Considerations

Blogger's Note: does not discuss hereditary syndrome (Lynch Syndrome)

open access
 

Diagnosis and Staging

The most common way in which UTUC is diagnosed is through a workup for hematuria. Less frequently, UTUC presents as flank pain, a flank mass, or an incidental finding on imaging obtained for other indications.^11,12 The standard investigation for hematuria includes urinary cytology, upper tract imaging, and cystoscopy.^11,12 First-line upper tract imaging consists of computed tomographic (CT) urography owing to its wide availability and its sensitivity and specificity for kidney stones and UTUC of more than 90%.¹³ In practice, upper tract imaging can be done with any number of alternatives based on resource availability, patient age, pretest risk, and local practice patterns. Although there has been enthusiasm for fluorodeoxyglucose ¹⁸F positron emission tomography/computed tomography (¹⁸FDG-PET/CT) in monitoring for recurrence of UTUC, its role as an initial imaging modality is limited.¹⁴ Similarly, magnetic resonance urography can accurately image soft-tissue lesions in the upper urinary tract and provides an option when iodinated contrast medium is contraindicated.¹⁵ As an initial screening test, urinary cytology has performed poorly, even in patients with high-grade UTUC and even when done in a selective fashion with barbotage.¹⁶ Hydronephrosis is a poor prognostic sign in UTUC, and the degree of hydronephrosis has been shown to be independently correlated with a negative prognosis.¹⁷ Regardless of the modality selected, no imaging method is completely accurate for the staging of localized UTUC or tumors that have spread to regional lymph nodes. Preoperative risk factors, histologic grade, and surgeon discretion all must play a role in the ultimate management of these tumors.....(UTUC)..... .

Public Health Approaches and Barriers to Educating Providers about Hereditary Breast and Ovarian Cancer Syndrome

Free Full-Text

podcast (7:36 min) Commentary: How Should We Manage the Financial Toxicity of Cancer Treatment?

mp3

podcast (9:20 min) Web-Based Technology Can Improve Patient Understanding and Preparedness to Discuss Cancer Clinical Trials: One Step Towards a Goal of Increased Enrollment

mp3

Editorial/Original Paper - Panel Testing Is Not a Panacea

Editorial - open access

  Public interest in genetics continues to be bolstered by media coverage, especially when endorsed by a celebrity. For example, when Angelina Jolie announced that she is a BRCA1 mutation carrier and elected to have bilateral prophylactic mastectomy, the general public was highly aware of her story, but did not have an improved understanding of the accompanying issues.¹⁴

....Consequently, although there is undoubtedly an economic and time advantage to panel genetic testing versus a step-wise approach, more testing is not necessarily better testing. Data such as those reported by Thompson et al¹ clearly identify clinically relevant genes beyond BRCA1 and BRCA2, and panel testing for genes with clear phenotypic overlap is justified. For example, evidence is mounting that PALB2 may be clinically indistinguishable from BRCA2 with regard to breast cancer risk¹⁰; this is further supported by the data in the study by Thompson et al¹, leading them to refer to PALB2 as an ideal panel gene. However, testing clinically for large numbers of genes with unclear clinical significance—or including genes that are not indicated on the basis of personal history, family history, or ethnicity just because we can—may be putting the cart before the horse. The issues currently being faced in clinical genetics will continue and will likely increase exponentially. As quickly as new genes are discovered, clinical laboratories will incorporate them into their panels. Alas, that proverbial horse may already be out of the barn. Therefore, particularly in this era of considerable uncertainty, complex, clinical panel-based genetic testing should be approached with extreme caution, and ideally only in consultation with trained genetics professionals.¹⁸

  

Footnotes

• abstract:  Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer

  abstract doi:10.1200/JCO.2015.65.0747

Vitamin D and Mortality

open access
 

Vitamin D and Specific Causes of Death

While we mainly report on vitamin D and all-cause mortality in this review, it is also important to briefly summarize the literature on specific causes of death, in order to gain more knowledge on the potential pathways and mechanisms that may link vitamin D and fatal events.

In observational studies, low 25(OH)D levels have been associated with increased risk of mortality due to cardiovascular diseases, cancer, respiratory disease, and non-vascular, non-cancer causes (33, 35, 36, 43, 44, 49, 73-76).

In the Mendelian randomization study by Afzal et al. it was reported that the odds ratio (95% CI) for cardiovascular mortality for each decrease of 20 nmol/l in plasma 25(OH)D was 1.13 (1.03 to 1.24), and the respective odds ratio (95% CI) for the genetically determined 25(OH)D levels was 0.77 (0.55 to 1.08) (68). This may suggest that the association between low 25(OH)D and cardiovascular deaths may not be causal. For cancer mortality, the respective odds ratios (95% CI) for each decrease of 20 nmol/l 25(OH)D was 1.10 (1.02 to 1.19) for plasma 25(OH)D and 1.43 (1.02 to 1.99) for genetically determined 25(OH)D. These data argue for causality with regard to the association of vitamin D deficiency and increased cancer mortality.

Meta-analyses of RCTs further support a causal effect of vitamin D on cancer mortality. In the Cochrane meta-analysis by Bjelakovic et al. involving 44,492 study participants from four trials, it was documented that vitamin D₃ supplementation statistically significantly reduced cancer mortality, with a risk ratio of 0.88 (95% CI=0.78-0.98). In line with this, Keum et al. also reported in their meta-analysis involving 44,260 participants that the RR for cancer mortality in the vitamin D-treated versus the placebo-treated group was 0.88 (95% CI=0.78-0.98) (77). These findings along with various molecular anticancer effects of vitamin D suggest that vitamin D supplementation may be useful for the prevention of cancer deaths. By contrast, there was no effect in meta-analyses on cancer incidence, suggesting that vitamin D might rather be relevant for the progression than for the initiation of cancer (77-79).

With regard to cardiovascular mortality, there was no significant effect of vitamin D as reported by Bjelakovic et al. (69). Although observational studies highlight vitamin D deficiency as a risk factor for cardiovascular events and strokes, most RCTs did not show any effect of vitamin D on these outcomes (69, 71, 80-83). It must, however, be acknowledged that no published RCT on vitamin D has been designed and statistically powered to assess cardiovascular events. Existing knowledge on the potential role of vitamin D for various other health outcomes have been extensively reviewed elsewhere (1-6, 84, 85).

 ....Regarding vitamin D research, there are some large ongoing RCTs on vitamin D in the general population that will significantly increase our knowledge on whether general vitamin D supplementation in the older population has an effect on clinical endpoints, including mortality (92, 93). It is, however, of concern that all large RCTs on vitamin D recruited participants regardless of their 25(OH)D levels, thereby increasing the probability of missing beneficial effects of vitamin D supplementation in individuals with low 25(OH)D concentrations. Null effects of such RCTs would definitely argue against major effect sizes but definite answers on whether vitamin D supplementation has relevant effects on mortality outcomes and other clinical endpoints should be derived from RCTs in severely vitamin D-deficient individuals, as this is the target population for vitamin D interventions (92-95).

Neuroendocrine Neoplasms of the Ovary: A Retrospective Study of the North Eastern German Society of Gynecologic Oncology (NOGGO)

abstract

Background/Aim: Neuroendocrine neoplasms (NEN) of the female genital tract account for 2% of gynecological cancers. The aim of this study was to share our experience of 11 primary neuroendocrine neoplasms of the ovary.

Patients and Methods: All patients who presented and/or were treated at our Institution with histologically-confirmed NEN of the ovary were included. Clinical data including tumor stage, diagnostic and therapeutic management and survival were assessed. Pathological specimens were critically reviewed.

Results: We identified 11 patients with NEN of the ovary consisting of nine neuroendocrine cancers and two carcinoids. Median age was 55.9 years. NEN were mostly poorly differentiated (72.4%). Primary surgery was performed in all patients. Adjuvant chemotherapy was administered in five patients consisting of platinum-based regimens. Median overall survival was 20 months.

Conclusion: We propose a diagnostic algorithm for NEN of the ovary and discuss possible treatments according to FIGO stages. Patients should be included in multicenter studies whenever possible.

A Biomarker Panel Increases the Diagnostic Performance for Epithelial Ovarian Cancer Type I and II in Young Women

open access

Results

The preoperative plasma levels of B7-H4 were higher in patients with EOC II tumors than in those with benign tumors (p<0.001) (Figure 1 and Table III) but no significant differences were found between EOC I or borderline tumors compared with benign tumors. The suPAR(II-III) levels were significantly lower in benign tumors compared to borderline, EOC I and EOC II tumors. HE4 and CA125 levels were significantly different in all comparisons between benign, borderline, EOC I and EOC II (Figure 1 and Table III).

Conclusion: The biomarker panel suPAR(II-III), HE4, CA125 and age in premenopausal women improved discrimination of malignant and benign ovarian tumors. The plasma levels of B7-H4 were increased in patients with EOC II compared to those with benign ovarian tumors. 

Predicting whether pelvic masses are benign or malignant has become more important as benign tumors now undergo laparoscopic surgery or conservative management. The suspected malignant tumors are referred to gynecological oncology centers for further evaluation and extensive ovarian cancer surgery, if needed to achieve macroscopic radical tumor reduction, improving survival. Subjective ultrasound evaluation of gray-scale and color Doppler images of pelvic masses, with pattern recognition, in the hands of expert ultra-sonographers have shown good prediction of discrimination between benign and malignant adnexal masses (1-3), but the general gynecologist or sonographer does not have that capability, not even after teaching sessions using the International Ovarian Tumour Analysis (IOTA) group scoring system (4) or IOTA simple rules (5).

In suspicion of malignancy, the most commonly used tumor marker, cancer antigen 125 (CA125), is not reliable due to low sensitivity in patients with early-stage ovarian cancer (6). CA125 also has a low specificity since it is often found increased in patients with benign endometriosis. The biomarker human epididymis protein 4 (HE4), alone and in combination with CA125 in the Risk of Ovarian Malignancy Algorithm (ROMA) algorithm, increases sensitivity in the distinction of ovarian carcinoma from benign disease. HE4 is approved by the United States Food and Drug Administration for monitoring recurrence or progressive disease in patients with epithelial ovarian cancer (EOC). We have shown that HE4 is an independent preoperative marker of poor prognosis in serous ovarian cancer (7). Although its physiological functions have not been fully identified, overexpression of the HE4 protein has been found mainly in serous and endometroid ovarian carcinomas (8).....

 A novel (new) ovarian tumor type and grading system has been proposed based on morphological and molecular genetics, which divides EOC into type I and type II tumors (11, 12). Low-grade serous, and endometrial carcinoma, clear cell cancer and mucinous carcinoma are classified as EOC type I (11). Generally, EOC type I carcinomas behave in an indolent manner and are more often confined to the ovary at diagnosis, with a stable genome and without TP53 mutations. EOC type II tumors are high-grade serous carcinomas which are more aggressive and genetically highly unstable, and the majority of carcinomas have TP53 mutations, hypermethylation, or dysfunction of breast cancer gene 1/2. The aggressive EOC type II tumors account for 75% of all EOCs and are responsible for 90% of deaths from the disease. It has also been suggested that type II EOCs develop in the fallopian tube at the conjunction to the ovary or the peritoneum (13).

A preoperative low cancer antigen 125 level (≤25.8 mg/dl) is a useful criterion to determine the optimal timing of interval debulking surgery...

abstract
A preoperative low cancer antigen 125 level (≤25.8 mg/dl) is a useful criterion to determine the optimal timing of interval debulking surgery following neoadjuvant chemotherapy in epithelial ovarian cancer

Objective The purpose of this study is to investigate the clinical characteristics to determine the optimal timing of interval debulking surgery following neoadjuvant chemotherapy in patients with advanced epithelial ovarian cancer. 

Methods We reviewed the charts of women with advanced epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer who underwent interval debulking surgery following neoadjuvant chemotherapy at our cancer center (Japan) from April 2006 to April 2014. 

Results There were 139 patients, including 91 with ovarian cancer [International Federation of Gynecology and Obstetrics (FIGO) Stage IIIc in 56 and IV in 35], two with fallopian tube cancers (FIGO Stage IV, both) and 46 with primary peritoneal cancer (FIGO Stage IIIc in 27 and IV in 19). After 3–6 cycles (median, 4 cycles) of platinum-based chemotherapy, interval debulking surgery was performed. 

Sixty-seven patients (48.2%) achieved complete resection of all macroscopic disease, while 72 did not. More patients with cancer antigen 125 levels ≤25.8 mg/dl at pre-interval debulking surgery achieved complete resection than those with higher cancer antigen 125 levels (84.7 vs. 21.3%; P< 0.0001). Patients with no ascites at pre-interval debulking surgery also achieved a higher complete resection rate (63.5 vs. 34.1%; P< 0.0001). Moreover, most patients (86.7%) with cancer antigen 125 levels ≤25.8 mg/dl and no ascites at pre-interval debulking surgery achieved complete resection. 

Conclusions A low cancer antigen 125 level of ≤25.8 mg/dl and the absence of ascites at pre-interval debulking surgery are major predictive factors for complete resection during interval debulking surgery and present useful criteria to determine the optimal timing of interval debulking surgery.

10 year report (website) Global Status of Advanced/ Metastatic Breast Cancer

10 year report

 summary
 

(global) A new survey finds 22-42% of Europeans believe women with advanced breast cancer should keep their disease a secret - social stigma

Medical News Today

 The report highlights the extent of the social stigma associated with incurable breast cancer. 22-42% people across five European countries (France 22%, UK 24%, Germany 27%, Poland 33%, Turkey 42%2) feel that patients with metastatic breast cancer should not talk about their disease with anyone other than their physician.¹ This social stigma is often driven by misunderstandings of the disease. 24-59% believe that metastatic breast cancer patients did not take preventive measures and are in some way responsible for their disease.^2....

 About the Global Decade Report
The Global Status of Metastatic Breast Cancer (mBC): A 2005 - 2015 Decade Report, developed by Pfizer in collaboration with the European School of Oncology (ESO), assesses the status of mBC in terms of patient care, the wider breast cancer environment and scientific advances and developments.
The analysis is based on three newly commissioned primary surveys examining current perceptions of the state of breast cancer among the general public, patient advocacy groups, Breast Cancer Centres, oncologists and nurses in 34 countries around the world. This included the first survey of the global population's perceptions of mBC fielded in 14 countries and involving 14,315 adults (both mBC patients and non-patients). In Europe, the UK, France, Germany, Poland and Turkey participated.

Ovarian cancer in Lynch syndrome; a systematic review (March 2016)

abstract
 

March 2016

Review

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Highlights

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In this systematic review 747 ovarian cancers in women with LS were evaluated.

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The mean age of diagnosis of ovarian cancer was 45.3 years (range 19–82 years).

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Most common histological types were endometrioid or clear cell carcinomas.

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65% of ovarian cancers were early stage (FIGO I/II) with a good overall survival.

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In six studies, 7/22 (32%) ovarian cancers were found during surveillance.

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Abstract

Objective

The aim was to systematically review the characteristics of ovarian cancer in women with Lynch syndrome (LS) and evaluate the role of surveillance in detection of ovarian cancer in LS.

Methods

All studies between 1979 and 2015 of women with ovarian cancer and LS or at 50% risk of LS were evaluated. Two reviewers independently evaluated eligible studies and extracted data on age at diagnosis, histological type, FIGO stage, and way of detection according to pre-specified criteria. The studies were assessed for quality using the Newcastle-Ottawa quality assessment scales.

Results

The quality score of the 49 identified studies was at least 6 out of 8 and provide clinical information on 747 LS women with ovarian cancer. The mean age at diagnosis was 45.3 (range 19–82) years. Most frequent mutations were MSH2 (47%) and MLH1 (38%). Histopathological data were available for 445 women. The most frequently reported histological type was mixed type (mucinous/endometrioid/clear cell carcinomas) (n = 136; 31%). Most tumours (281, 65%) were diagnosed at an early stage (FIGO I/II). Six studies evaluating the effect of surveillance of ovarian cancer, reported that seven of 22 (32%) ovarian cancers were found during surveillance, 6/7 (86%) were detected at an early stage.

Conclusion

This systematic review describes that ovarian cancer in women with LS has a wide age-range of onset, is often diagnosed at an early stage with frequently endometrioid/clear cell histology. Data about the role of surveillance in detection of ovarian cancer in women with LS are scarce however detection at an early stage seems possible.

press release March 14th: Many Cancer Survivors Experience Financial Burdens that Negatively Affect their Health and Quality of Life

press release

 Many Cancer Survivors Experience Financial Burdens that Negatively Affect their Health and Quality of Life

An analysis of US data from 2011 indicates that nearly 29 percent of cancer survivors are financially burdened as a result of their cancer diagnosis and/or treatment. Published early online in CANCER, a peer-reviewed journal of the American Cancer Society, the study also reveals that such hardships can have lasting physical and mental effects on cancer survivors.
Few studies have assessed the impact of cancer-related financial burden on cancer survivors’ quality of life. To investigate, Hrishikesh Kale, MS, and Norman Carroll, PhD, of Virginia Commonwealth University School of Pharmacy, analyzed 2011 Medical Expenditure Panel Survey data on 19.6 million cancer survivors. They considered financial burden to be present if one of the following problems was reported: borrowed money/declared bankruptcy, worried about paying large medical bills, unable to cover the cost of medical care visits, or other financial sacrifices.
The researchers found that nearly 29 percent of US cancer survivors reported at least one financial problem resulting from cancer diagnosis, treatment, or lasting effects of that treatment. Of all cancer survivors in the analysis, 21 percent worried about paying large medical bills, 11.5 percent were unable to cover the cost of medical care visits, 7.6 percent reported borrowing money or going into debt, 1.5 percent declared bankruptcy, and 8.6 percent reported other financial sacrifices.
Cancer survivors who faced such financial difficulties had lower physical and mental health-related quality of life, higher risk for depressed mood and psychological distress, and were more likely to worry about cancer recurrence compared with cancer survivors who did not face financial problems. Also, as the number of financial problems reported by cancer survivors increased, their quality of life continued to decrease and their risk for depressed mood, psychological distress, and worries about cancer recurrence continued to increase.
The investigators also identified the effects of different types of financial problems on quality of life: declaring bankruptcy was associated with a 20 percent to 25 percent reduction in quality of life, while worrying about paying large medical bills was associated with a reduction of 6 percent to 8 percent.
“Our results suggest that policies and practices that minimize cancer patients’ out-of-pocket costs can improve survivors’ health-related quality of life and psychological health,” said Dr. Carroll. “Reducing the financial burden of cancer care requires integrated efforts, and the study findings are useful for survivorship care programs, oncologists, payers, pharmaceutical companies, and patients and their family members.”
Mr. Kale noted that oncologists should consider selecting treatments that are less expensive but similar in effectiveness, discuss treatment costs with patients, and involve patients in making decisions about their therapy. “Also, cancer patients and family members should educate themselves regarding survivorship issues, coverage and benefit design of their health plans, and organizations that provide financial assistance. Cancer survivorship care programs can identify survivors with the greatest financial burden and focus on helping them cope with psychological stress, anxiety, and depression throughout their journey with cancer.”

(9 min) podcast - defining rare cancers/alliances (the Lancet/Oncology)

mp3

Recurrent Pseudomembranous Colitis in an Ovarian Cancer Patient Undergoing Carboplatin Chemotherapy

open access

Abstract
Background. Diarrhea is a common problem in ovarian cancer patients undergoing chemotherapy and Clostridium difficile infection has been identified as a cause. The proper diagnosis and treatment of diarrhea are critical to patient care, especially to prevent the serious complications from a severe Clostridium difficile infection (CDI). Case. We present a heavily pretreated ovarian cancer patient who developed recurrent pseudomembranous colitis while receiving carboplatin chemotherapy. Despite treatment with oral metronidazole for fourteen days, the patient’s diarrhea relapsed and colonoscopy revealed extensive pseudomembranous colitis. The infection eventually resolved with the combination of oral vancomycin and metronidazole.
Conclusions. Diarrhea is a common problem in patients undergoing chemotherapy for ovarian cancer. Management requires obtaining the proper diagnosis. Clostridium difficile associated pseudomembranous colitis must be part of the differential diagnosis. Treatment must be sufficient to prevent relapses of the Clostridium difficile infection to prevent serious consequences in an already vulnerable patient population.

1. Introduction
Clostridium difficile infection (CDI) was recognized in 1978 as the etiology of antibiotic associated diarrhea and subsequent pseudomembranous colitis [1, 2]. In modern practice, clinical suspicion for CDI remains high when a patient develops diarrhea in close temporal relation to a course of antibiotics. However, in addition to antibiotics, chemotherapy has been confirmed as an independent risk factor for development of CDI and recently chemotherapy has become an established independent risk factor for healthcare associated Clostridium difficile colonization [3, 4].

The purpose of this paper is to describe a case of recurrent Clostridium difficile pseudomembranous colitis associated with single agent carboplatin chemotherapy in a woman with ovarian cancer......

Cediranib in patients with relapsed platinum-sensitive ovarian cancer (ICON6): a randomised, double-blind, placebo-controlled phase 3 trial

open access

Background

Angiogenesis is a validated clinical target in advanced epithelial ovarian cancer. Cediranib is an oral antiangiogenic vascular endothelial growth factor receptor 1–3 inhibitor that has shown antitumour activity in recurrent ovarian cancer. We assessed efficacy and safety of cediranib in combination with platinum-based chemotherapy and as continued maintenance treatment in patients with first relapse of platinum-sensitive ovarian cancer.

Methods

In this randomised, three-arm, double-blind, placebo-controlled phase 3 trial, we randomly assigned patients aged 18 years or older with relapsed platinum-sensitive ovarian cancer at 63 centres in Australia, Canada, New Zealand, Spain, and the UK. Participants received up to six cycles of platinum-based chemotherapy (once every 3 weeks) then entered a maintenance phase.....

Research in context

Evidence before this study

In 2003, we published the results of the International Collaborative for Ovarian Neoplasia (ICON) 4 trial in The Lancet, showing the value of platinum-combination treatment for women relapsing more than 6 months after completing first-line treatment for ovarian cancer. This set a new standard of care with an improvement in overall survival, but the benefit was slight. In around 2006, unpublished data began to emerge showing that inhibitors of angiogenesis, blocking either the vascular endothelial growth factor (VEGF) ligand or its receptor could lead to shrinkage of ovarian tumours and delayed disease progression. We designed a three-arm, placebo-controlled, randomised trial (ICON6) in collaboration with the Gynaecological Cancer InterGroup adding the VEGF receptor tyrosine kinase inhibitor cediranib to chemotherapy and then continued as maintenance treatment. No previous trials of maintenance treatment with a molecularly targeted treatment in ovarian cancer had been done, although during this time, trials with the monoclonal antibody bevacizumab were in development for first-line treatment and for women with first relapse......

Refers To

• John Norrie

• ICON-6: the danger of changing study design midstreamThe Lancet, Volume 387, Issue 10023, 12–18 March 2016, Pages 1031-1032 

  open access 

• • ......These design changes should not have been necessary, and clinical trials should be better structured to make sure this does not recur.

    The original study design promised more reliable evidence, but instead of randomly assigning roughly 2000 participants, the study underwent a major revision with just 387 participants randomly assigned because the drug company involved (AstraZeneca) decided (on Sept 14, 2011) to cease commercial development of cediranib, owing to negative findings for overall survival in three pivotal phase 3 studies on different cancers.^{3, 4 and 5} With insufficient remaining drug stock and its short shelf life, as well as AstraZeneca being unwilling to manufacture additional supplies, a fundamental redesign (or complete abandonment) became necessary.......