OVARIAN CANCER and US

Blog Archives: Nov 2004 - present

#ovariancancers



Special items: Ovarian Cancer and Us blog best viewed in Firefox

Search This Blog

Wednesday, November 11, 2015

Are We Closer to Preventing Ovarian Cancer? + Viewpoint



medscape

Improving the management of post-operative acute pain: priorities for change



open access

...Poor management in the case of post-operative acute pain can contribute to medical complications such as pneumonia, deep vein thrombosis, infection, chronic pain and depression7,8. It is also one of the three most common medical causes of delayed discharge after ambulatory surgery9. In addition to the significant personal suffering and social burden that result, considerable financial expense is incurred, both directly in extra healthcare costs and indirectly as a result of absenteeism, lost production and welfare payments. All post-operative acute pain should therefore be prevented if possible or, if not, accurately diagnosed and then treated promptly and effectively to improve patient comfort, avoid complications, prevent the development of chronic pain, and reduce the economic burden on society10. However, despite the numerous guidelines on managing acute pain produced over the past two decades11–14, the proven benefits of the ‘pain-free hospital’ initiative15 and the many effective analgesics now available, surveys suggest that for many patients there has been little improvement over this period16–18.....

Tuesday, November 10, 2015

open access: Germline Variants in Targeted Tumor Sequencing Using Matched Normal DNA



Blogger's Note: see tables for additional detailed information

JAMA Oncology - open access

 Conclusions and Relevance  Germline variants are common in individuals undergoing tumor-normal sequencing and may reveal otherwise unsuspected syndromic associations.

 .....In some patients, a cancer-predisposing variant is present in the “normal” DNA, either inherited or as an early postzygotic event. The burden of germline variants differs by tumor type, although it can be substantial (eg, mutations of the Fanconi pathway genes can be seen in 20% of patients with ovarian cancer).6 Most germline susceptibility variants are not targetable, although there are exceptions (eg, PARP inhibitors in patients with BRCA1 and BRCA2 mutation-associated cancers). Efforts to characterize germline susceptibility are therefore usually ancillary to the primary purpose of clinical tumor mutation profiling. However, knowledge of these variants could guide the preventive care of the patient or the patient’s family, even if the knowledge does not influence the treatment of the patient’s cancer.7....


At a Glance
  • Targeted tumor sequencing with a panel of 341 genes and matched normal DNA in 1566 individuals with advanced malignant neoplasms revealed presumed pathogenic germline variants (PPGVs) in about 16% of individuals.
  • Most PPGVs (80.5%; 95% CI, 75.1%-85.0%) were in genes related to cancer susceptibility.
  • The PPGVs in genes previously designated as clinically actionable were seen in 5.0% (95% CI, 4.1%-6.2%) of individuals.
  • Most cancer-susceptibility PPGVs were retained in the tumor (91.9%; 95% CI, 87.3%-95.0%).
  • Almost all individuals carried germline variants of uncertain significance that will require significant curation to determine clinical significance.

    Supplement.
    eTable 1. Distribution and demographics of cases across 68 cancer types (n=1566)
    eTable 2. Genes on MSK-IMPACT (n=341)
    eTable 3. Summary of OMIM annotated genes on MSK-IMPACT compared by modes of inheritance
    eTable 4. OMIM genes and associated syndromes on MSK-IMPACT panel
    eTable 5. Presumed pathogenic germline variant classifications in OMIM genes (including Cancer and ACMG gene subsets) included on MSK-IMPACT
    eTable 6. Genes with variant totals for single nucleotide variants, insertion or deletions, and copy number variants (SNV, Indels, CNVs) grouped by potential phenotype in the patient
    eTable 7. Presumed pathogenic germline variants in OMIM genes (including Cancer and ACMG gene subsets) included on MSK-IMPACT per subject
    eTable 8. Presumed pathogenic germline variants in OMIM genes and status of PPGV in tumor
    eTable 9. Aggregate presumed pathogenic germline variant totals by disease site and gene
    Supplemental Content
 

In Flanders Fields



"In Flanders Fields" (ref. Wiki) is a war poem in the form of a rondeau, written during the First World War by Canadian physician Lieutenant-Colonel John McCrae. He was inspired to write it on May 3, 1915, after presiding over the funeral of friend and fellow soldier Alexis Helmer, who died in the Second Battle of Ypres. According to legend, fellow soldiers retrieved the poem after McCrae, initially dissatisfied with his work, discarded it. "In Flanders Fields" was first published on December 8 of that year in the London-based magazine Punch.
It is one of the most popular and most quoted poems from the war. As a result of its immediate popularity, parts of the poem were used in propaganda efforts and appeals to recruit soldiers and raise money selling war bonds. Its references to the red poppies that grew over the graves of fallen soldiers resulted in the remembrance poppy becoming one of the world's most recognized memorial symbols for soldiers who have died in conflict. The poem and poppy are prominent Remembrance Day symbols throughout the Commonwealth of Nations, particularly in Canada, where "In Flanders Fields" is one of the nation's best-known literary works. The poem also has wide exposure in the United States, where it is associated with Memorial Day.....
  
Poem
The poem handwritten by McCrae. In this copy, the first line ends with "grow", differing from the original published version.
 
An autographed copy of the poem from In Flanders Fields and Other Poems. Unlike the printed copy in the same book, McCrae's handwritten version ends the first line with "grow".
 
The first chapter of In Flanders Fields and Other Poems, a 1919 collection of McCrae's works, gives the text of the poem as follows:[9]

In Flanders fields the poppies blow
Between the crosses, row on row,
That mark our place; and in the sky
The larks, still bravely singing, fly
Scarce heard amid the guns below.

We are the Dead. Short days ago
We lived, felt dawn, saw sunset glow,
Loved and were loved, and now we lie
In Flanders fields.

Take up our quarrel with the foe:
To you from failing hands we throw
The torch; be yours to hold it high.
If ye break faith with us who die
We shall not sleep, though poppies grow
In Flanders fields.

QOL and mental health among women with ovarian cancer: examining the role of emotional and instrumental social support seeking



Abstract

 The purpose of the present study was to examine the role of emotional and instrumental social support seeking in the quality of life (QOL) and mental health of women with ovarian cancer. Participants were recruited through the Pennsylvania Cancer Registry, and one hundred women took part in a mail questionnaire that collected information on their demographics, medical status, social support seeking, QOL and mental health including anxiety, depression and stress. Hierarchical linear regression analyses were conducted to assess the influence of emotional and instrumental social support seeking on QOL and mental health. After controlling for remission status, greater emotional social support seeking was predictive of higher overall QOL, social/family QOL, functional QOL and lower depression scores. Instrumental social support seeking was not significant in the models. The results illustrate that social support seeking as a coping mechanism is an important consideration in the QOL and mental health of women with ovarian cancer. Future studies should examine the psychological and behavioral mediators of the relationship to further understand the QOL and mental health of women with ovarian cancer.

CSIOVDB: a microarray gene expression database of epithelial ovarian cancer subtype



open access
  
ABSTRACT
Databases pertaining to various diseases provide valuable resources on particular genes of interest but lack the molecular subtype and epithelial-mesenchymal transition status. CSIOVDB is a transcriptomic microarray database of 3,431 human ovarian cancers, including carcinoma of the ovary, fallopian tube, and peritoneum, and metastasis to the ovary. The database also comprises stroma and ovarian surface epithelium from normal ovary tissue, as well as over 400 early-stage ovarian cancers. This unique database presents the molecular subtype and epithelial-mesenchymal transition status for each ovarian cancer sample, with major ovarian cancer histologies (clear cell, endometrioid, mucinous, low-grade serous, serous) represented. Clinico-pathological parameters available include tumor grade, surgical debulking status, clinical response and age. The database has 1,868 and 1,516 samples with information pertaining to overall and disease-free survival rates, respectively. The database also provides integration with the copy number, DNA methylation and mutation data from TCGA. CSIOVDB seeks to provide a resource for biomarker and therapeutic target exploration for ovarian cancer research.


Querying a gene of interest
CSIOVDB seeks to provide users with the expression profiles of certain genes of interest relevant to ovarian cancer; in particular, the molecular subtype distribution and subtype-specific outcomes in terms of overall survival and disease-free (progression- and recurrence-free) survival......

Association between MMP-12-82A/G polymorphism and cancer risk: a meta-analysis



Abstract
 

BACKGROUND:

Numerous studies have focused on the association between MMP-12-82A>G polymorphism and cancer risk, but produced inconsistent results. Therefore, we performed a meta-analysis of case-control study to evaluate the association of MMP-12-82A>G polymorphism and cancer risk.

METHODS:

A systematic literature search was conducted among PubMed, Web of Science, Science Direct, China National Knowledge Infrastructure (CNKI) and Wangfang databases updated on May 1st, 2015. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of association between this polymorphism and cancer risk.

RESULTS:

A total of seventeen case-control studies with 7,450 cases and 7,348 controls were identified and analyzed. Overall, there was no statistically significant association between MMP-12-82A>G polymorphism and increased risk of cancer under all genetic models. Subgroup analysis by ethnicity observed that there is no strong relationship between MMP-12-82A>G polymorphism and cancer risk among Asian and European populations. Furthermore, stratified analysis based on the source of control revealed no statistically significant association between MMP-12-82A>G polymorphism and cancer risk either in hospital-based or population-based studies. However, when we stratified analysis based on cancer type, significant association was found in ovarian cancer, but not in other types of cancer.

CONCLUSION:

This meta-analysis suggests that MMP-12-82A>G polymorphism is not significantly associated with overall cancer risk. However, MMP-12-82A>G polymorphism may increase the susceptibility to ovarian cancer.

Association of Preoperative Thrombocytosis and Leukocytosis With Postoperative Morbidity and Mortality Among Patients With Ovarian Cancer



Abstract


OBJECTIVE:

To examine whether preoperative thrombocytosis or leukocytosis is associated with increased postoperative morbidity or mortality.

METHODS:

Patients with ovarian cancer undergoing primary surgery from 2005 to 2012 were identified from the American College of Surgeons National Surgical Quality Improvement Project. Thrombocytosis was defined as platelets greater than 450,000/mm and leukocytosis as white blood cells greater than 10,000/mm. We examined 30-day postoperative complications and mortality. Descriptive statistics and adjusted multivariable logistic regression were used for analysis.

RESULTS:

We identified 1,072 patients. The incidence of thrombocytosis was 9.6%, leukocytosis was 18.7%, and 4.9% had both.

Morphological and Immunohistochemical Reevaluation of Tumors Initially Diagnosed as Ovarian Endometrioid Carcinoma With Emphasis on High-grade Tumors



abstract

 Ovarian endometrioid carcinomas (OEC) of low grade have characteristic morphologic features, but high-grade tumors can mimic high-grade serous and undifferentiated carcinomas. We reviewed tumors initially diagnosed as OEC to determine whether a combination of pathologic and immunohistochemical features can improve histologic subclassification. Tumors initially diagnosed as OEC were reviewed using World Health Organization criteria. We also noted the presence of associated confirmatory endometrioid features (CEFs): (i) squamous metaplasia; (ii) endometriosis; (iii) adenofibromatous background; and (iv) borderline endometrioid or mixed Mullerian component. A tissue microarray was constructed from 27 representative tumors with CEF and 14 without CEF, and sections were stained for WT-1, p16, and p53. Of 109 tumors initially diagnosed as OEC, 76 (70%) tumors were classified as OEC. The median patient age was 55 years, and 75% of patients were younger than 60 years. Ninety-two percent presented with disease confined to the pelvis, and 87% of tumors were unilateral. The median tumor size was 11.8 cm. Only 3% of tumors were high grade (grade 3of 3). Eighty percent of cases had at least 1 CEF, and 59% had at least 2 CEFs. Eleven percent overexpressed p16, 0% overexpressed p53, and 3% expressed WT-1. Only 10% of patients died of disease at last follow-up. Thirty-three (33) tumors, or 30% of tumors originally classified as endometrioid, were reclassified as serous carcinoma (OSC). The median patient age was 54.5 years, and 59% of patients were younger than 60 years of age. Only 27% had disease confined to the pelvis at presentation, 52% of tumors were unilateral, and the median tumor size was 8 cm. Associated squamous differentiation, endometrioid adenofibroma, and endometrioid or mixed Mullerian borderline tumor (CEFs) were not present in any case, but 6% of patients had endometriosis. Approximately one half of the reclassified OSC demonstrated SET-pattern morphology (combinations of glandular, cribriform, solid, and transitional cell-like architecture) and were immunophenotypically indistinguishable from OSCs with papillary architecture. Sixty percent of OSC overexpressed p16, 50% overexpressed p53, and 82% expressed WT-1. At last follow-up, 52% had died of disease. Compared with OSC, OEC patients more frequently presented below 60 years of age (P=0.046), had low-stage tumors (P<0.001), were more frequently unilateral (P<0.001), more frequently had synchronous endometrial endometrioid carcinomas (P<0.001); and had no evidence of disease at last follow-up (P<0.001). Their tumors were of lower grade (P<0.001), had more CEFs (P<0.001), and less frequently overexpressed p16 and p53 (P=0.003 and P<0.001, respectively) and less frequently expressed WT-1 (P<0.001). This analysis emphasizes the diagnostic value of CEFs, the presence of a low-grade gland-forming endometrioid component, and WT-1 negativity, as valid, clinically relevant criteria for a diagnosis of OEC. Glandular and/or cribriform architecture alone may be seen in both OECs and OSCs and are therefore not informative of diagnosis. Further study is needed to elaborate the characteristics of the exceedingly rare high-grade OEC.

Plasma biomarker analysis of ovarian cancer patients undergoing immunotherapy with therapeutic cancer vaccine DPX-Survivac



Journal for ImmunoTherapy of Cancer
 

Background

Immune based therapies for cancer are emerging as promising strategies to treat a number of malignancies. A more thorough biomarker assessment of the patients may provide insights into the variability in response to such immune therapies. In a Phase I/Ib clinical trial with the survivin-targeting vaccine DPX-Survivac, we showed the induction of robust immune responses in ovarian cancer patients. In this study, we investigated the potential of proteomic and metabolomic analysis of plasma to identify surrogate biomarkers for efficacy, recurrence and adverse events (AE) in vaccine recipients.....

Monday, November 09, 2015

Calls for more funding for rare cancers



(Australia) media
 

AN AUSTRALIAN medical expert says a different approach to treatment of rare cancers is needed, with research showing rare cancers contribute to 30% of deaths from the disease while less than 20% of funding goes to them.
University of South Australia's Professor Ian Olver said in the Medical Journal of Australia, published Monday, that research showed more than 80% of cancer research funding went to blood cancers and five solid cancers (breast, colorectal, prostate, melanoma and lung), while rare cancers such as pancreatic, ovarian and brain received less funding.
Rare cancers are defined as having fewer than six cases per 100,000 head of population a year.
"If less research is being performed to provide data, and the low incidence of rare cancers makes large randomised clinical trials impractical, there are few evidence-based guidelines regarding rarer cancers to which clinicians can refer," Prof Olver said.
He said ovarian cancer was a good example of how approaches to rare cancer treatment needed to evolve.
He said common cancers which had improved survival rates, including breast and bowel, had screenings for early detection.
But a population screening test would be difficult to achieve for ovarian cancer, he said.
"The heterogeneity of ovarian cancer suggests that a population screening test based on a panel of biomarkers will be difficult to achieve."

Is Neoadjuvant Chemo Justified in Ovarian Cancer?



Onclive

.... Herzog said ongoing studies, including the NCIC CTG OV.21 and MRC-UK ICON8 trials, are hoping to add further clarity to the use of neoadjuvant chemotherapy in ovarian cancer....

Dose Delays, Dose Reductions, and Relative Dose Intensity in Patients With Cancer Who Received Adjuvant or Neoadjuvant Chemotherapy in Community Oncology Practices



abstract

Background: A wide variety of myelosuppressive chemotherapy regimens are used for the treatment of cancer in clinical practice. Neutropenic complications, such as febrile neutropenia, are among the most common side effects of chemotherapy, and they often necessitate delays or reductions in doses of myelosuppressive agents. Reduced relative dose intensity (RDI) may lead to poorer disease-free and overall survival.  
Methods: Using the McKesson Specialty Health/US Oncology iKnowMed electronic health record database, we retrospectively identified the first course of adjuvant or neoadjuvant chemotherapy received by patients without metastases who initiated treatment between January 1, 2007, and March 31, 2011. For each regimen, we estimated the incidences of dose delays (≥7 days in any cycle of the course), dose reductions (≥ 15% in any cycle of the course), and reduced RDI (<85% over the course) relative to the corresponding standard tumor regimens described in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines).  
Results: This study included 16,233 patients with 6 different tumor types who received 1 of 20 chemotherapy regimens. Chemotherapy dose delays, dose reductions, and reduced RDI were common among patients treated in community oncology practices in the United States, but RDI was highly variable across patients, regimens, and tumor types (0.486–0.935 for standard tumor regimen cohorts). Reduced RDI was more common in older patients, obese patients, and patients whose daily activities were restricted.  
Conclusions: In this large evaluation of RDI in US clinical practice, physicians frequently administered myelosuppressive agents at dose intensities lower than those of standard regimens.

Editorial: Silicone Gel Breast Implants: What We Know About Safety After All These Years



partial view 

Controversy over the safety of silicone breast implants has been raging for more than half a century. In this issue, Balk and colleagues report a comprehensive systematic review on long-term health outcomes in women with silicone gel breast implants. The editorialists note that given the absence of solid evidence for association between silicone implants and well-defined disease, we should refocus research efforts to understand the symptoms that some women with implants report.

Editorial: Working Toward a Solution: The Unanswered Questions About Silicone Gel Breast Implants



partial view (subscriber based publication)

Long-Term Health Outcomes in Women with Silicone Gel Breast Implants: A Systematic ReviewLong-Term Health Outcomes With Silicone Gel Breast Implants



abstract: Long-Term Health Outcomes in Women with Silicone Gel Breast Implants: A Systematic ReviewLong-Term Health Outcomes With Silicone Gel Breast Implants | Annals of Internal Medicine

 
Background: Silicone gel breast implants were removed from the U.S. market for cosmetic use in 1992 owing to safety concerns. They were reintroduced in 2006, with a call for improved surveillance of clinical outcomes.
Purpose: To systematically review the literature regarding specific long-term health outcomes in women with silicone gel breast implants, including cancer; connective tissue, rheumatologic, and autoimmune diseases; neurologic diseases; reproductive issues, including lactation; offspring issues; and mental health issues (depression and suicide).

5 Reasons Why The Future Looks Bright For Humans And Bleak For Cancer (article)



(media) article: Joan Massagué
 


Sunday, November 08, 2015

Immunotherapy Not Ready for Prime Time in Ovarian Cancer



Markman: onclive

Early promising responses seen with immune checkpoint inhibitors for patients with ovarian cancer still need to be validated in larger randomized trials before a conclusion is made regarding their true efficacy, according to a presentation by Maurie Markman, MD, at the 33rd Annual Chemotherapy Foundation Symposium.

 “The checkpoint inhibitors are not ready for prime time yet in ovarian cancer. It's not because there's evidence that they don't work—it's just that there's no evidence at all,” said Markman, president of Medicine and Science at the Cancer Treatment Centers of America. “You could not think of a more appropriate tumor type to explore the concept of immunotherapy than ovarian cancer. Unfortunately, as we've all learned, it's much more complicated.”....

Different Types Of Ovarian Cancer Have Different Causes



science news
 
.....Professor Charlie Swanton, Chair of the 2015 NCRI Cancer Conference, said, "We've known for some time that the number of children a woman has, and her use of contraception, can influence her risk of ovarian cancer, so this research provides important further detail about different types of the disease.
"Ovarian cancer - like many other cancers - is not one disease, but different diseases that are grouped together because of where they start. It's important to know what affects the risk of different types of ovarian cancer and what factors impact this. We now need to understand the mechanisms behind these findings to develop some way to extend this lower risk to all women, regardless of how many children they have."

ImmunoGen (IMGN) Refines Drug Targeting for Ovarian Cancer Patients (Based on these new findings, ImmunoGen is planning a phase II study of mirvetuximab soravtansin which will enroll ovarian cancer patients with tumors containing medium and high levels of folate receptors. The study is expected to start before the end of the year (mirvetuximab soravtansin)



financial news

..... Based on these new findings, ImmunoGen is planning a phase II study of mirvetuximab soravtansin which will enroll ovarian cancer patients with tumors containing medium and high levels of folate receptors. The study is expected to start before the end of the year.

A comparison of the toxicity and tolerability of two IP chemotherapy regimens for advanced-stage epithelial ovarian cancer



 Blogger's Note: abstract does not detail followup period eg. PFS

Abstract
 

OBJECTIVES:

Randomized controlled trials (RCTs) in optimally cytoreduced epithelial ovarian cancer (EOC) patients have demonstrated an impressive survival benefit of intraperitoneal (IP) platinum over intravenous (IV), but its use has been limited by significant toxicity from cisplatin. The aim of this study was to compare the toxicity and tolerability of IP cisplatin to IP carboplatin in women with optimally cytoreduced EOC.

METHODS:

Retrospective analysis of 141 women with EOC who underwent optimal surgical cytoreduction followed by IV paclitaxel and IP cisplatin or IP carboplatin was performed. Toxicities of the two treatment regimens were compared. As a secondary outcome, overall survival (OS) and progression-free survival (PFS) probabilities were obtained using the Kaplan-Meier estimate; the log-rank test was used to compare survival curves.

RESULTS:

Of the 141 patients, 77 (54.6%) received IP cisplatin and 64 (45.4%) received IP carboplatin. Eighty-six percent received at least 4cycles of IP chemotherapy. IP cisplatin was associated with significantly more grade 3 nausea and vomiting (10.4% vs 1.6%, p=0.033), grade 3 neuropathy (7.8% vs 0%, p=0.013) and grade 2-3 neutropenia (22.1% vs 9.4%, p=0.042). No difference in PFS (p=0.602) or OS (p=0.107) was found between the groups.

CONCLUSION:

IP chemotherapy had a high completion rate in both groups of patients. IP carboplatin required a less resource intense protocol and was tolerated better than IP cisplatin with less gastrointestinal, neurologic and hematologic toxicities.

Prevalence of sexual dysfunction after risk-reducing salpingo-oophorectomy



abstract


OBJECTIVES:

To determine the prevalence of sexual dysfunction in women after risk-reducing salpingo-oophorectomy (RRSO) and to assess factors which may influence sexual wellbeing following this procedure.

METHODS:

This work is a cross-sectional study of women who underwent RRSO at a tertiary gynecologic oncology unit between January 2009 and October 2014. Data collection involved a comprehensive questionnaire including validated measures of sexual function, sexual distress, relationship satisfaction, body image, impact of event, menopause specific quality of life, and general quality of life. Participants were invited to undergo blood testing for serum testosterone and free androgen index (FAI).

Q&A: Advances in Genetic Testing: A Focus on Hereditary Cancer



pdf

Saturday, November 07, 2015

Smoking may modify the association between neoadjuvant chemotherapy and survival from ovarian cancer



abstract


Highlights

  • The interaction between smoking and chemotherapy on survival from ovarian cancer is unknown.
  • Smoking reduced overall and progression-free survival among patients with mucinous ovarian cancer receiving adjuvant chemotherapy.
  • Smoking reduced progression-free survival among all ovarian cancer patients receiving neoadjuvant chemotherapy.

Abstract

Objective

Tobacco smoking by cancer patients is associated with increased mortality. Less is known of the impact of smoking on recurrence risk and interaction with chemotherapy treatment. We examined these associations in ovarian cancer.

Methods

Patients were identified from the Alberta Cancer Registry between 1978 and 2010 and were oversampled for less-common histologic ovarian tumor types. Medical records were abstracted for 678 eligible patients on lifestyle, medical and cancer treatment, and review of pathology slides was performed for 605 patients. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazard models adjusted for age at diagnosis, race, stage and residual disease.

Results

Among patients receiving adjuvant chemotherapy (N = 432), current smoking was significantly associated with shorter duration of overall (OS; HR, 8.56; 95% CI, 1.50–48.7) and progression-free (PFS; HR, 5.74; 95% CI, 1.05–31.4) survival from mucinous ovarian cancer only. There was no significant association between neoadjuvant chemotherapy and survival. However,

Where cancers spread to depends on cellular ‘soil prep’



Cancer Research UK - Science blog

As challenges go, understanding how cancers spread around the body is a biggy.
We know the locations tumour cells end up in isn’t random – breast cancer cells tend to head for the lungs, liver, bones or brain, for example.
But how they do this has remained a bit of a mystery.
In 1889, London doctor Stephen Paget planted the idea of ‘seed and soil’. He believed that tumour cells find the body’s ‘fertile ground’, seeding their secondary roots in the tissues that are most welcoming.
It’s a compelling idea, yet many believe it’s too simple a view of the problem.
But a new US study – published in the journal Nature  (abstract)– digs deeper into this theory, finessing the idea with some convincing data to back it up.
It turns out that instead of finding already fertile soil, cancer cells might actually be ploughing their own furrow in advance of spreading there. And, crucially, the discovery could one day help make predictions about whether a tumour might spread.
We asked our experts what they thought of the new findings......

Critical Shortage of African American Medical Oncologists in the United States



open access

The Association of American Medical Colleges (AAMC) reported that in 2013 only 2.3% of oncologists in the United States were African American.1 In early 2015, the American Society of Clinical Oncology (ASCO) released 2013 data showing that African Americans will likely continue to be seriously under-represented in medical oncology and that African Americans composed only 4.0% of hematology/oncology fellows in the United States.2 Data from 2012 show a similar pattern for percentages of African American physicians in hematology/oncology in internal medicine (4.0%), pediatric hematology/oncology (4.6%), and radiation oncology (4.2%).3.....

Risk factors for neuroendocrine neoplasms: a systematic review/meta-analysis



open access

(page 7- pdf)  
A case-control study of prospectively enrolled patients with pancreatic NEN from Arizona (USA), reported that cases were more likely than controls to have a family member with pancreatic NEN (p=0.024), gallbladder cancer (p=0.024), gastric cancer (p=0.01), sarcoma (p=0.02), and ovarian cancer (p=0.04) [15]. No other consistent associations between pancreatic NEN and cancers at other organ sites were found. 

 

Analysis of Heritability/Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types



 Blogger's Note: not terribly useful without open access

Abstract
 
Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. 

Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. 

Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl 2, on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking  Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. 

Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.


Benefit, Risk, and Outcomes in Drug Development: A Systematic Review of Sunitinib



Abstract

Background: Little is known about the total patient burden associated with clinical development and where burdens fall most heavily during a drug development program. Our goal was to quantify the total patient burden/benefit in developing a new drug.
Methods: We measured risk using drug-related adverse events that were grade 3 or higher, benefit by objective response rate, and trial outcomes by whether studies met their primary endpoint with acceptable safety. The differences in risk (death rate) and benefit (overall response rate) between industry and nonindustry trials were analyzed with an inverse-variance weighted fixed effects meta-analysis implemented as a weighted regression analysis. All statistical tests were two-sided.
Results: We identified 103 primary publications of sunitinib monotherapy, representing 9092 patients and 3991 patient-years of involvement over 10 years and 32 different malignancies. In total, 1052 patients receiving sunitinib monotherapy experienced objective tumor response (15.7% of intent-to-treat population, 95% confidence interval [CI] = 15.3% to 16.0%), 98 died from drug-related toxicities (1.08%, 95% CI = 1.02% to 1.14%), and at least 1245 experienced grade 3–4 drug-related toxicities (13.7%, 95% CI = 13.3% to 14.1%). Risk/benefit worsened as the development program matured, with several instances of replicated negative studies and almost no positive trials after the first responding malignancies were discovered.
Conclusions: Even for a successful drug, the risk/benefit balance of trials was similar to phase I cancer trials in general. Sunitinib monotherapy development showed worsening risk/benefit, and the testing of new indications responded slowly to evidence that sunitinib monotherapy would not extend to new malignancies. Research decision-making should draw on evidence from whole research programs rather than a narrow band of studies in the same indication.

Prognostic value of 18F-FDG PET/CT volumetric parameters in recurrent epithelial ovarian cancer



abstract


OBJECTIVE:

Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from 18F-FDG PET/CT are emerging prognostic biomarkers in various solid neoplasms. These volumetric parameters and the SUVmax have shown to be useful criteria for disease prognostication in preoperative and post-treatment epithelial ovarian cancer (EOC) patients. The purpose of this study was to evaluate the utility of 18F-FDG PET/CT measurements to predict survival in patients with recurrent EOC.

A Systematic Review of Symptoms for the Diagnosis of Ovarian Cancer



Abstract

Context

Ovarian cancer is common and has significant morbidity and mortality, partly because it is often diagnosed at a late stage. This study sought to determine the accuracy of individual symptoms and combinations of symptoms for the diagnosis of ovarian cancer.

Evidence acquisition

MEDLINE was searched, identifying 2,492 abstracts, reviewing 71 articles in full, and ultimately identifying 17 studies published between 2001 and 2014 that met the inclusion criteria......... Data were analyzed in 2015.

Evidence synthesis

Most studies were at high risk of bias, primarily because of case-control design or differential verification bias. The highest positive likelihood ratios (LRs+) were found for presence of abdominal mass (LR+, 30.0); abdominal distension or increased girth (LR+, 16.0); abdominal or pelvic pain (LR+, 10.4); abdominal or pelvic bloating (LR+, 9.3); loss of appetite (LR+, 9.2); and a family history of ovarian cancer (LR+, 7.5). No symptoms were helpful at ruling out ovarian cancer when absent. The Ovarian Cancer Symptom Index was validated in five studies and (after excluding one outlier with different inclusion criteria) was 63% sensitive and 95% specific (LR+, 12.6; LR–, 0.39). Two other symptom scores had not been validated prospectively.

Conclusions

Several individual signs and symptoms significantly increase the likelihood of ovarian cancer when present. More work is needed to validate decision rules and develop new decision support tools integrating risk factors, symptoms, and possibly biomarkers to identify women at increased ovarian cancer risk.

Immunohistochemical characterization of appendiceal mucinous neoplasms and the value of SATB2 in their distinction from primary ovarian mucinous tumors



abstract
 

AIMS:

The distinction between primary ovarian mucinous tumors and appendiceal mucinous neoplasms metastatic to the ovary can be challenging given the overlap of morphologic features and immunohistochemical expression of traditional markers. SATB2 has been recently described as a sensitive and specific marker of colorectal epithelium. Its expression in appendiceal mucinous tumors and its role in their distinction from ovarian neoplasms have not been fully characterized.

CONCLUSIONS: 

 SATB2 is frequently expressed in appendiceal mucinous neoplasms. In the context of a mucinous neoplasm involving the ovary, any SATB2 positivity should raise the possibility of appendiceal origin. Expression of CK20, CDX2 and MUC2 supports appendiceal origin only when diffuse and strong. These and other markers such as CK7 and PAX8 are recommended in the work-up of ovarian mucinous tumors with any clinical or pathologic features suspicious for secondary origin.

Friday, November 06, 2015

Clinical follow-up and breast and ovarian cancer screening of true BRCA1/2 noncarriers: a qualitative investigation



abstract
 

PURPOSE:

Most women from BRCA1/2 mutation-positive families who did not inherit the familial mutation have breast and ovarian cancer risks similar to those of women of the same age in the general population. However, recent studies suggest that some of these noncarriers may exhibit screening practices that may be considered as excessive compared to general population screening guidelines. Reasons for such tendencies remain largely unknown. This study aims to better understand how the implications of a noncarrier status are explained to these women and how their own realization of this status affects their screening behaviors.

METHODS:

A qualitative study was conducted with five focus groups (n = 28) in Quebec City and Montreal, Canada.

Thursday, November 05, 2015

The Fallopian Tube in the 21st Century: When, Why, and How to Consider Removal (open access)



open access - Editorial

In January 2015, based on the available data on ovarian carcinogenesis and the safety of salpingectomy, both the American College of Obstetricians and Gynecologists (ACOG) and the American Cancer Society (ACS) recommended that surgeons should discuss the potential benefits of the prophylactic removal of the Fallopian tubes (FTs) for permanent contraception or during surgeries for benign pathologies with every woman at population risk for ovarian cancer (OC) [1, 2].
This is a potential revolution. Until the end of the 20th century, salpingectomy was considered to be an unworthy appendix of more complex gynecological surgeries or as an “emergency” measure to treat life-threatening conditions....

Impact of mutational status on survival in low-grade serous carcinoma of the ovary or peritoneum



open access

 ....Although low-grade serous carcinoma is associated with superior survival outcomes compared with high-grade serous carcinoma and other high-grade ovarian cancers, such as clear cell and high-grade endometrioid subtypes, nevertheless, over 70% of women with low-grade serous carcinoma relapse and ultimately succumb to their cancer. Thus, it is important that we continue to concentrate on better understanding the biology of this rare subtype while concomitantly working toward improving treatment.

AICR: Top Fall Spices for Cancer Prevention (and how to use them)



eNews

 Spices, Spices, Spices
Research is looking at the potent phytochemicals in spices and their role in cancer prevention. Most studies use far higher amounts then you would eat, but spices can transform an entire dish with the power of a pinch or a teaspoon.
Try these five spices in your cooking to add flavor to your cancer-protective meals.

Know Your Risk: (quiz) low white blood cell count/infections during chemo



CDCF PCI

Know Your Risk and Take our Risk Assessment Test.

Your answers to a few questions will help estimate your risk for developing a low white blood cell count (a condition called neutropenia) and infections during your chemotherapy.  This risk is highest when your white blood cell count is at its lowest.

Click on the appropriate link below to take the test:
 Know the Actions You Can Take to Protect Yourself
Since a fever may be your body's only sign of an infection,
it's very important that you call your doctor immediately
if you have a temp of 100.4 F or higher for more than 1 hour, or a
one-time temp of 101 F or higher.
 

(2015 election) Canada creates science-minister post : Nature News



Nature News

 Canada's new prime minister, Justin Trudeau, took office on 4 November — and as one of his first acts, created the post of Minister of Science.
Kirsty Duncan, a medical geographer at the University of Toronto in Canada, will be the first to hold the job. Duncan, who contributed to the 2001 report of the Intergovernmental Panel on Climate Change, has also written a book about her expedition to Norway to determine the cause of the 1918 Spanish flu epidemic.
Her appointment marks a change from the government of former prime minister Stephen Harper. His administration placed oversight of science in the hands of a junior minister of state in the Industry Canada department.
“Harper (former prime minister) collapsed the purview of science into the purview of industry, and we've seen a dramatic decline of pure science and public interest research as a result,” says Carol Linnitt, an environmental policy analyst at the Vancouver-based non-profit environmental group DeSmog Canada.
Scientists and science groups say that they are excited by Duncan's appointment but want to know more about the Minister of Science's responsibilities. “A real minister! And someone with a PhD!” says Marc Saner, former director of the Institute for Science, Society and Policy at the University of Ottawa. “From the point of view of image, it’s great. How this works in practice, I don’t know.” He suspects that Duncan will work to ensure that the government conducts research in areas that universities and businesses are not exploring.......

More appointments

Trudeau has also appointed Navdeep Bains, a financial analyst, as Minister of Industry, Science and Economic Development.
“If we take it at face value, we now have two ministers responsible for science,” says Rees Kassen, a biologist at the University of Ottawa and chair of the Partnership Group for Science and Engineering, an Ottawa-based association of science and engineering organizations.....


From nature.com (background)

Single Injectable Agent Spots Tumors and Destroys Them (in research lab)



Medgadget
 
At Oregon State University scientists are using silicon naphthalocyanine as both an imaging and cancer destruction agent, allowing for a single compound to be used to quickly find and target tumor tissue. Reporting at the American Association of Pharmaceutical Scientists in Orlando, Florida, the team presented pre-clinical findings of how silicon naphthalocyanine was used to destroy ovarian tumors in laboratory animals, seemingly without side effects and without the cancer returning.
Silicon naphthalocyanine glows when illuminated with near infrared light, while heating up and creating reactive oxygen species. It’s delivered inside the copolymer PEG-PCL that gathers around cancer cells, pointing to the location of the tumors. Once settled, therapy can begin by administering near infrared light to the areas where the tumors are. The particles eventually breakdown and are excreted by the body.
Study in Chemistry of Materials: Naphthalocyanine-Based Biodegradable Polymeric Nanoparticles for Image-Guided Combinatorial Phototherapy…

Smartphone Pilot Signals White Coat Syndrome Solution



eHealthNews

 A smartphone pilot study has highlighted a potential solution for white coat syndrome - the medical phenomenon responsible for sending some patients’ blood pressure soaring in the GP surgery. Patient Angela Howard was able to prove that her surgery blood pressure test results were uncharacteristically high and not an accurate reflection of her actual health in a month-long trial of the Personal Health Record (PHR) within EMIS Health's Patient Access app....

Unusual primary tumors presenting as papillary carcinomas metastatic to the neck



abstract

 The presence of a metastatic papillary carcinoma in the neck is presumptive evidence of a primary thyroid neoplasm since neck metastases of other primary tumors are uncommon. Immunohistochemical studies may be required to diagnose these metastases. We report 2 cases in which an unrelated tumor mimicked a thyroid malignancy. Both patients had been referred for evaluation of enlarged lymph neck nodes without any other symptoms. In both cases, a lymph node biopsy identified a metastatic papillary adenocarcinoma that was believed to be consistent with a thyroid primary. Thyroidectomy was not performed in either case. Further investigations led to the diagnosis of other primary tumors that were unrelated to the thyroid; the unrelated primaries were an ovarian serous tumor in one patient and a papillary renal cell carcinoma in the other.

Immunohistochemistry in the Diagnosis of Mucinous Neoplasms Involving the Ovary: The Added Value of SATB2 and Biomarker Discovery



abstract
 Immunohistochemistry in the Diagnosis of Mucinous Neoplasms Involving the Ovary: The Added Value of SATB2 and Biomarker Discovery Through Protein Expression Database Mining.

 Immunohistochemistry is frequently used to identify ovarian mucinous neoplasms as primary or metastatic; however, there is significant overlap in expression patterns. We compared traditional markers (CK7, CK20, CDX2, PAX8, estrogen receptor, β-catenin, MUC1, MUC2, and MUC5AC) to 2 novel proteins identified through mining of the Human Protein Atlas expression database: SATB2 and POF1B. The study cohort included 49 primary gastrointestinal (GI) mucinous adenocarcinomas (19 colorectal, 15 gastric, 15 pancreatobiliary), 60 primary ovarian mucinous neoplasms (19 cystadenomas, 21 borderline tumors, 20 adenocarcinomas), and 19 metastatic carcinomas to the ovary (14 lower and 5 upper GI primaries). Immunohistochemistry was performed on tissue microarrays, scored and interpreted as negative (absent or focal/weak) or positive. Metastatic tumors were frequently unilateral (42.8% of tumors from lower and 40% of tumors from upper tract) and ≥10 cm (85.7% of tumors from lower and 80% of tumors from upper tract). CK7 was positive in 88.5% upper GI and 88.3% primary ovarian compared with 24.3% lower GI neoplasms. CK20 and CDX2 were positive in 84.8% and 100% of lower GI tumors, respectively; however, expression was also common in upper GI (CK20 42.8%, CDX2 50%) and primary ovarian neoplasms (CK20 65.7%, CDX2 38.3%).

Cytokeratin 5–Positive Cells Represent a Therapy Resistant subpopulation in Epithelial Ovarian Cancer (2)




CK5 marks cisplatin-resistant ovarian cancer Source: University of Colorado Anschutz Medical Campus
Summary:
Protein cytokeratin 5 (CK5), known to be a marker of poor prognosis in breast cancer, also marks ovarian cancers likely to be resistant to the common chemotherapy cisplatin, new research confirms.
   "It's interesting that CK5-positive cells pop up as bad actors across many cancer types. Now the challenge is to find a functional role for the protein in cancer. What's functionally different about those cells?" Sartorius says.

abstract
 
Objective: Cytokeratin 5 (CK5) is an epithelial cell marker implicated in stem and progenitor cell activity in glandular reproductive tissues and endocrine and chemotherapy resistance in estrogen receptor (ER)+ breast cancer. The goal of this study was to determine the prevalence of CK5 expression in ovarian cancer and the response of CK5+ cell populations to cisplatin therapy.
Materials and Methods: Cytokeratin 5 expression was evaluated in 2 ovarian tissue microarrays, representing 137 neoplasms, and 6 ovarian cancer cell lines. Cell lines were treated with IC50 (half-maximal inhibitory concentration) cisplatin, and the prevalence of CK5+ cells pretreatment and posttreatment was determined. Proliferation of CK5+ versus CK5 cell populations was determined using 5-bromo-2′-deoxyuridine incorporation. Chemotherapy-induced apoptosis in CK5+ versus CK5 cells was measured using immunohistochemical staining for cleaved caspase-3.
Results: Cytokeratin 5 was expressed in 39.3% (42 of 107) of epithelial ovarian cancers with a range of 1% to 80% positive cells. Serous and endometrioid histologic subtypes had the highest percentage of CK5+ specimens. Cytokeratin 5 expression correlated with ER positivity (38 of 42 CK5+ tumors were also ER+). Cytokeratin 5 was expressed in 5 of 6 overall and 4 of 4 ER+ epithelial ovarian cancer cell lines ranging from 2.4% to 52.7% positive cells. Cytokeratin 5+ compared with CK5 cells were slower proliferating. The prevalence of CK5+ cells increased after 48-hour cisplatin treatment in 4 of 5 cell lines tested. Cytokeratin 5+ ovarian cancer cells compared with CK5 ovarian cancer cells were more resistant to cisplatin-induced apoptosis.
Conclusions: Cytokeratin 5 is expressed in a significant proportion of epithelial ovarian cancers and represents a slower proliferating chemoresistant subpopulation that may warrant cotargeting in combination therapy.


Wednesday, November 04, 2015

Importance of Universal Mismatch Repair Protein Immunohistochemistry in Patients with Sebaceous Neoplasia as an Initial Screening Tool for Muir-Torre Syndrome



abstract

 Summary
Muir Torre Syndrome (MTS), a Lynch Syndrome (LS) variant, is characterized by sebaceous neoplasia plus one or more malignancies, typically colon cancer. The significance of DNA mismatch repair (MMR) deficiency detection by immunohistochemistry (IHC) in colorectal carcinomas is well-established, and is recommended as a screening tool for LS in newly diagnosed colorectal carcinomas. In comparison, literature on IHC application to detect MMR proteins (MLH1, MSH2, MSH6, and PMS2) in sebaceous neoplasia has been less studied, and has been derived almost exclusively from tertiary care centers. Herein we describe the largest series to date characterizing MMR deficiency in sebaceous neoplasms, as well as the relative frequencies of each deficiency. 216 consecutive sebaceous neoplasms (216 patients) were analyzed from a community practice setting (133 sebaceous adenomas, 68 sebaceomas, 15 sebaceous carcinomas). 143 were MMR deficient (66%), of which 90 were MSH2/MSH6 deficient (63%), 27 MLH1/PMS2 deficient (19%), 22 MSH6 deficient (15%), and 4 PMS2 deficient (3%). MMR deficiency was significantly associated with site, with tumors off the head and neck more likely to be MMR deficient (specificity 96%). In contrast to prior reports, no significant trend in MMR deficient versus non-deficient tumors was seen in age at presentation (median age, 68 vs. 66), tumor infiltrating lymphocytes (TILs), or tumor type. Given the low sensitivity of age < 60 y (30%), location off head and neck (41%), or presence of TILs (29%) in MMR deficiency detection, IHC screening programs should test all sebaceous neoplasms for MMR deficiency, regardless of their clinicopathologic features.

Medical treatment of early stage and rare histological variants of epithelial ovarian cancer





ecancermedicalscience - The open access journal from the European Institute of Oncology and the OCEI

 Conclusion
Epithelial ovarian cancer is not a single disease, but a heterogeneous group of neoplasms. Classification on the basis of morphological, immunohystochemical, and genetic analysis and progresses in understanding the molecular background of carcinogenesis contributes to identify specific and unique tumours subtypes with different behaviour, prognosis, and response to chemotherapy.
The current indications for the medical treatment of epithelial ovarian cancer are the same, independently from histological subtypes. It is hoped that the current one size-for-all chemotherapy regimens will evolve into genetic-specific treatments based on molecular markers.

 
Table 2. Characteristics of clear cell, mucinous, and endometrioid ovarian carcinoma in comparison.

Evaluation of Perioperative Medication Errors/Adverse Drug Events (anesthesia 79.3% preventable)



open access (pdf)

  Results: A total of 277 operations were observed with 3,671 medication administrations of which 193 (5.3%; 95% CI, 4.5 to 6.0) involved a ME and/or ADE. Of these, 153 (79.3%) were preventable and 40 (20.7%) were nonpreventable. The events included 153 (79.3%) errors and 91 (47.2%) ADEs. Although 32 (20.9%) of the errors had little potential for harm, 51 (33.3%) led to an observed ADE and an additional 70 (45.8%) had the potential for patient harm. Of the 153 errors, 99 (64.7%) were serious, 51 (33.3%) were significant, and 3 (2.0%) were life-threatening

Rerouted, not derailed: resuming a young life after cancer



Patient-Voice (open for comments)

 What do survivors want?
Knowledge is power. But oncologists have to bear in mind that their former patients may feel ambivalent about being followed up all their lives. How can they be effectively monitored, without constantly reminding them of their former ‘ill’ status? How can their psychological and social wellbeing be supported in addition to their physical wellbeing? How can a global prevention programme be set up? After finishing their treatment, most patients vanish from the medical system.



Oncologists have to bear in mind that their former patients may feel ambivalent about being followed up all their lives


Many never want to set foot in a hospital again, they want to move on. Once they turn 18, survivors will tend to look to general practitioners for their healthcare, but many GPs have no idea about the kind of follow up that is needed.....

Genetic Cancer Susceptibility Testing: Increased Technology, Increased Complexity



JCO

Efficacy and tolerability of oral oxycodone and oxycodone/naloxone com



open access (small study included gyn patients)

 Background: World Health Organization step III opioids are required to relieve moderate-to-severe cancer pain; constipation is one of the most frequent opioid-induced side effects. A fixed combination, prolonged-release oxycodone/naloxone (OXN), was developed with the aim of reducing opioid-related gastrointestinal side effects. The objective of this study was to compare the efficacy and safety of prolonged-release oxycodone (OXY) alone to OXN in opioid-naïve cancer patients with moderate-to-severe pain.....

Scoring No Goal — Further Adventures in Transparency (physician scorecards eg. ratings)



Perspectives: NEJM

 The irony in hailing the scorecard as a victory for transparency is that its purported objectivity obscures its methodologic limitations and the complexity of quality itself. No amount of transparency can overcome the fact that, when it comes to what we value, we don't all see eye to eye. The real promise of transparency, then, lies in finding better ways to let our patients see what we see.