OVARIAN CANCER and US

Friday, April 29, 2016

New gene testing technology finds cancer risks 'hiding in plain sight'

"When a woman with a family history of breast cancer sees her physician, they want to know if they have a mutation in breast/ovarian cancer genes," says Rogan. "All of the patients that we studied had been sequenced for BRCA1 or BRCA2. The causative cancer gene variants are hiding in plain sight in these and other cancer genes, but the original testing laboratory didn't recognize them. Our approach can reveal gene variants that might explain their increased risk for cancer."

Journal References:

Eliseos J. Mucaki, Natasha G. Caminsky, Ami M. Perri, Ruipeng Lu, Alain Laederach, Matthew Halvorsen, Joan H. M. Knoll, Peter K. Rogan. A unified analytic framework for prioritization of non-coding variants of uncertain significance in heritable breast and ovarian cancer. BMC Medical Genomics, 2016; 9 (1) DOI: 10.1186/s12920-016-0178-5
Natasha G. Caminsky, Eliseos J. Mucaki, Ami M. Perri, Ruipeng Lu, Joan H.M. Knoll, Peter K. Rogan. Prioritizing Variants in Complete Hereditary Breast and Ovarian Cancer (HBOC) Genes in Patients Lacking knownBRCAMutations. Human Mutation, 2016; DOI: 10.1002/humu.22972

SSRI use and clinical outcomes in epithelial ovarian cancer

abstract

Selective serotonin reuptake inhibitor (SSRI) (antidepressants) use is common among ovarian cancer patients. We examined the effect of SSRIs on survival and progression in ovarian cancer patients and effects of 5-HT on ovarian cancer cell (OCC) proliferation. Ovarian cancer patients from a 6-site study between 1994 and 2010 were included. Cox proportional hazards models were used for multivariate analysis. SSRI use was associated with decreased time to disease recurrence (HR 1.3, CI 1.0-1.6, p=0.03), but not overall survival (HR 1.1, CI 0.9-1.3, p=0.56). Compared to normal ovarian cells, most OCCs had elevated 5-HT2A receptor mRNA expression (up to 1600 fold greater expression). Clonogenic survival increased in cells treated with 10 uM (1.6 fold, p<0.001) and 20uM (1.9 fold, p=0.018) 5-HT. Mice receiving 5-HT injections had increases in tumor weight (p=0.07) and nodules (p=0.08) with increased Ki67 expression. Injections with sertraline doubled mean tumor weight in mice (p=0.16). 5-HT and sertraline both increased Ki67 expression in mouse tumors (p < 0.001).Patients using SSRIs had significantly decreased time to disease progression. It is possible that SSRIs alter serotonin levels in the tumor microenvironment, resulting in activation of proliferation pathways. Further characterization of serotonergic pathways in ovarian cancer is recommended to demonstrate safety of these medications.

Extrapancreatic solid pseudopapillary tumors: A clinicopathological analysis of two cases

Eabstract

Solid pseudopapillary tumors (SPTs) are unusual neoplasms that mostly occur in the pancreas, and predominantly affect young women. As a low-grade malignant neoplasm of the exocrine pancreas, they occasionally metastasize, usually to the liver or peritoneum. It has been reported that <1% of SPTs are primary extrapancreatic SPTs. In the present study, we present two rare, but conspicuous extrapancreatic SPTs. Both occurred in young women, and showed good prognoses following surgery. One was a recurrent SPT of the pancreas that metastasized to the ovary, and the other was a distinct primary neoplasm that arose in the retroperitoneal area. The pathological features of the two tumors, including solid and pseudopapillary growth patterns with pale or eosinophilic cytoplasm, were characteristic of SPTs of the pancreas. However, in the case of the metastatic ovarian tumor, focal necrosis and an increased nuclear-to-cytoplasmic ratio were observed. The presence of positive nuclear-cytoplasmic β-catenin, the loss of membranous E-cadherin expression, and a perinuclear punctate CD99 staining pattern on immunohistochemistical analysis, were essential features for diagnosis. The aim of the present study was to compare the morphological and immunohistochemical features of these tumors with those typical of pancreatic SPTs, and to raise awareness that SPTs are able to metastasize to unusual sites, and may also arise as primary tumors outside the pancreas, which may lead to diagnostic dilemmas.

The Role of Angiogenesis in the Persistence of Chemoresistance in Epithelial Ovarian Cancer

abstract

Objective: Chemoresistance remains a major challenge in the treatment of ovarian cancer. As part of a survival mechanism, tumor cells have been shown to release proangiogenic factors, such as vascular endothelial growth factor (VEGF), through a mechanism that involves the upregulation of hypoxia-induced factor (HIF)-1α. The objective of this study was to compare the expression of VEGF and its receptors (R1 and R2) as well as HIF-1α in chemoresistant epithelial ovarian cancer (EOC) cells to their chemosensitive counterparts and determine their impact on angiogenesis.

Conclusion: Cisplatin- and taxotere-resistant EOC cells are characterized by lower VEGF, VEGF receptors, and HIF-1α, and decreased angiogenesis. These findings may indicate a decrease in drug delivery at the tumor site, hence allowing the persistence of chemoresistant EOC cells.

Thursday, April 28, 2016

No need to fast before a cholesterol test

Science news

FULL STORY

New research from Denmark, Canada and the US involving more than 300,000 individuals suggests that patients do not need to check their cholesterol levels on an empty stomach. So far fasting has been required before cholesterol and triglyceride measurement in all countries except Denmark, where non-fasting blood sampling has been used since 2009.....

Journal Reference:

Børge G. Nordestgaard, Anne Langsted, Samia Mora, Genovefa Kolovou, Hannsjörg Baum, Eric Bruckert, Gerald F. Watts, Grazyna Sypniewska, Olov Wiklund, Jan Borén, M. John Chapman, Christa Cobbaert, Olivier S. Descamps, Arnold von Eckardstein, Pia R. Kamstrup, Kari Pulkki, Florian Kronenberg, Alan T. Remaley, Nader Rifai, Emilio Ros, Michel Langlois. Fasting is not routinely required for determination of a lipid profile: clinical and laboratory implications including flagging at desirable concentration cut-points—a joint consensus statement from the European Atherosclerosis Society and European . European Heart Journal, April 2016 DOI: 10.1093/eurheartj/ehw152

PARP Inhibitors in Epithelial Ovarian Cancer: State of Art and Perspectives of Clinical Research

open access

Homologous recombination (HR) and base excision repair (BER) are two of the major DNA-repair pathways.

.....Phase III trials are currently ongoing to further evaluate the role of PARP inhibitors in patients with EOC with mutated BRCA_1-2 or high-grade serous or endometrioid histological type after platinum-based chemotherapy (Table III).

Germline BRCA_1-2 testing should be offered to all women with non-mucinous EOC, regardless of age and family history (44, 95). However, HR deficiency has been observed not only in germline BRCA_1-2 mutation carriers, but also in patients with EOC with somatic mutations of BRCA₁ or BRCA₂, epigenetic silencing of BRCA₁, and loss of function of other genes (40, 41). Approximately half of all high-grade EOCs are HR-deficient, and therefore additional biological and clinical investigations are strongly warranted to identify this subset of tumors (46, 47, 96). Once HR deficiency becomes amenable to routine testing, a larger group of patients with EOC than those with mutated BRCA_1-2 will benefit from the use of PARP inhibitors (97).

5 articles: Postoperative Adhesions - Impact, Risks, Burden and Complications of Adhesions

Postoperative Adhesions | Impact, Risks, Burden and Complications of Adhesions

Impact and Burden of Adhesions - Video (ovarian; IP chemo; laparotomy; laparoscopy; small bowel obstructions....)

Video (plain english language)

Adhesions are fibrous bands of internal scar tissue that can cause tissues and organs that are not otherwise normally connected to stick together.¹ Adhesions are the most common and frequent complication of abdominal surgery and form in more than 90% of abdominal surgery patients.^1,2

Risks and Complications of Adhesions

Patients with adhesions suffer from major short- and long-term postoperative complications, which place a burden on patients, surgeons, and healthcare systems, including:

Small bowel obstruction (SBO)³
Female infertility³
Chronic abdominopelvic pain³
Reoperation for adhesiolysis (surgical removal of adhesions)³
Longer operation times and associated increased risk of complications³
Limitations on future therapeutic options³
Increased mortality risk^4,5

While the utmost care can and should be taken during surgery to prevent adhesion formation, adhesions—part of the natural tissue healing process—are not always preventable by surgical technique alone.^3,6 While not all adhesions are problematic, many are symptomatic but go undiagnosed as the root cause of comorbidities.^3,4

Clinicopathologic characteristics and survival of patients with gyn malignancies metastatic to the brain

abstract

OBJECTIVE:

No standardized treatment strategies exist for patients with gynecologic malignancies complicated by brain metastases.....

METHODS:

This retrospective cohort study included 100 gynecologic cancer patients with brain metastases treated at our institution between January 1990 and June 2009....

RESULTS:

On univariate analysis, primary ovarian disease, CA-125<81 units/mL at brain metastases diagnosis, and isolated versus multi-focal metastases were all associated with longer survival.....

CONCLUSIONS:

Multi-modality therapy may lead to improved clinical outcomes, and VEGF therapy should be investigated in treatment of brain metastases.

Wednesday, April 27, 2016

Radiology: Inherited Renal Carcinomas (note refers to Lynch Syndrome-breast....)

open access - overview/imaging

Abstract
Hereditary forms of kidney carcinoma account for 5–8 % of all malignant kidney neoplasms....

See page 12 for Lynch Syndrome (eg. UTUC)

example:

Fig. 8. Metachronous urothelial carcinoma in the pelvocaliceal
system in a 60-year-old female with Lynch syndrome,
who presented with hematuria and had a history of endometrial
cancer, colon polyps, bladder cancer, and ovarian cancer.
(A) CT urogram shows small filling defects in the right upper
renal collecting system (arrow), which was proved to be grade
2 (of 3) urothelial carcinoma after ureteroscopic biopsy and
subsequently treated with endourologic laser tumor ablation.
(B) At age 64, CT urogram reveals a new large tumor arising
from the left renal pelvis, which was proved to be grade 2 (of 3)

FDA grants orphan drug designation to VAL-083 for ovarian cancer

VAL-083 for ovarian cancer

IP Therapy Proves Non-Superior to IV/Bevacizumab Combination in Ovarian Cancer

targeted oncology item

.... “All arms had substantial toxicity,” Walker said. “Neurotoxicity was equally high in all arms. We reserve judgment on recommendations until survival is available. IP cisplatin probably shouldn’t be combined with bevacizumab because it causes severe hypertension.”

An analysis of patient-reported outcomes (PROs)—quality of life, neuropathy, nausea, fatigue, and abdominal discomfort—showed consistently lower scores among patients in the cisplatin arm.

PRO scores did not differ appreciably between the two carboplatin arms, with the exception of slower improvement in abdominal discomfort in patients treated with IP carboplatin.

References

Walker JL, Brady MF, DiSilvestro PA, et al. A phase III clinical trial of bevacizumab with IV versus IP chemotherapy in ovarian, fallopian tube and primary peritoneal carcinoma NCI-supplied agent(s): bevacizumab (NSC #704865, IND #7921) NCT01167712 a GOG/NRG trial (GOG 252). Presented at: 2016 SGO Annual Meeting. March 19-22, 2016. San Diego, CA. Late-breaking abstract.
Armstrong DK, Bundy B, Wenzel L, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006;354(1):34-43.

Exclusion of Residents From Surgery-Intensive Care Team Communication (Sunnybrook/UofT)

abstract
Exclusion of Residents From Surgery-Intensive Care Team Communication: A Qualitative Study

Objective

Communication competency is an important aspect of postgraduate training and patient care delivery in all specialties and clinical domains. This study explored staff surgeon and intensivist perceptions of and experiences with residents’ communication with a view toward fostering high quality interspecialty team communication in the surgical intensive care unit.

Design

A qualitative study using semistructured interviews. Data were analyzed iteratively and inductively as per standard qualitative thematic approach.

Setting

University of Toronto, Toronto, Canada.

Participants

A total of 15 staff surgeons and intensivists who collaborate in patient care in the surgical intensive care unit.

Results

The phenomenon of “resident bypass” emerged, resulting from staff surgeon and intensivist perceptions that residents threaten the quality of interspecialty team communication. Clear patterns and preferences for resident exclusion from this communication were present. A total of 5 interrelated drivers of resident bypass were discovered: lack of trust, lack of specialized knowledge, poor system design, need for timely communication, and residents’ inadequate contribution to decision-making. Surgical and intensive care staff were dissatisfied with the structure of residents’ roles in interspecialty team communication. Concerns about communication gaps, patient care continuity, and patient safety were expressed.

Conclusions

Surgical and intensive care staff exclude residents from interspecialty team communication for the benefit of patient safety and care continuity, but this limits opportunities for residents to develop communication skill and competence. Efforts are needed to effectively integrate surgery and intensive care residents in interspecialty attending-resident communication in ways that are meaningful for both patient care and postgraduate training. The implications for medical education are discussed.

Putting Doctors and Patients on the Same Page (6 million OpenNotes secure web portal - U.S.)

CommonwealthFund

Five years ago, Harvard researchers convinced 100 primary care physicians to try something novel — share the notes they made during and after office visits with their patients. Patients already had the legal right to access their records, but it involved a lot of request forms and tedious faxing, and few knew about or took advantage of their rights. Moreover, doctors were reluctant to impart their own notes, even as secure email messaging had made sharing lab test results, medication records, and other parts of the medical record easier.

The Harvard trial was therefore groundbreaking, and its main finding — that patients will actually read and learn from their doctors’ notes — catalyzed a national movement known as OpenNotes. Today, some 6 million Americans have easy access to their medical records, including clinical notes, through secure web portals. So what has this open relationship meant for doctors and their patients?.....

Redesigned Genetics Home Reference Web Site Offers New Look and Feel, Improved Navigation

Redesigned Genetics Home Reference Web Site Offers New Look and Feel, Improved Navigation. NLM Technical Bulletin. 2016 Mar–Apr

Defining the polyposis/colorectal cancer phenotype associated with the Ashkenazi GREM1 duplication

abstract
Defining the polyposis/colorectal cancer phenotype associated with the Ashkenazi GREM1 duplication: counselling and management recommendations

Summary

Hereditary mixed polyposis is a genetically heterogeneous, autosomal dominant condition with adenomatous, hyperplastic and juvenile polyps. We conducted a comprehensive clinical evaluation of a large Ashkenazi Jewish family with this phenotype and performed extensive genetic testing. As seen in one previous report, a 40 kb duplication upstream of GREM1 segregated with the polyposis/colon cancer phenotype in this kindred. Our study confirms the association of GREM1 with mixed polyposis and further defines the phenotype seen with this mutation. This gene should be included in the test panel for all Jewish patients with mixed polyposis and may be considered in any Ashkenazi patient with unexplained hereditary colon cancer when mutations in other hereditary colon cancer genes have been ruled out.

Biomarkers Associated with Checkpoint Inhibitors

abstract

Checkpoint Inhibitors (CPI), namely anti-CTLA4 and anti-PD1/PD-L1 antibodies, demonstrated efficacy across multiple types of cancer. However, only subgroups of patients respond to these therapies. Additionally, CPI can induce severe immune-related adverse events (irAE). Biomarkers that predict efficacy and toxicity may help define the patients who may benefit the most from these costly and potentially toxic therapies. In this study, we review the main biomarkers that have been associated with the efficacy (pharmacodynamics and clinical benefit) and the toxicity (irAE) of CPIs in patients.

open access (pdf)

.....Patients who seem to benefit most from CPIs are those presenting with immunogenic tumors (i.e. with a high mutational load), pre-existing immune response (intratumoral immune infiltrate) and the immune escape ligands being targeted (i.e. PD-L1 for patients treated with anti-PD-1/PD-L1 Abs). Nevertheless, these biomarkers are not perfect. In the future, better knowledge of the mechanisms of action of CPIs in vivo should help us identify other biomarkers in order to define patients who will benefit most from these effective but costly and potentially toxic drug

Faecal Occult Blood Tests Show Lower Colorectal Cancer Detection Rates in the Proximal Colon in Colonoscopy-verified Diagnostic Studies

open access Medscape
Systematic Review With Meta-analysis - Faecal Occult Blood Tests Show Lower Colorectal Cancer Detection Rates in the Proximal Colon in Colonoscopy-verified Diagnostic Studies

Aliment Pharmacol Ther. 2016;43(7):755-764

This study has some limitations. First, the detection rates of CRC in the proximal or distal colon may be different across different age, gender, race and number of samples. A previous study showed that age had a greater effect on proximal CRC;^[44] it may affect the diagnostic performance in different anatomic location. Secondly, there exist numerous brands of FOBTs.^[45] Diagnostic performance may be verified from brands to brands; however, subgroup analysis of FOBT brands could not be performed due to lack of studies. Third, this study included both symptomatic and asymptomatic patients; pooled results may not reflect FOBT performance under screening setting. Inclusion of symptomatic patients might overestimate the sensitivity. Also, for studies recruiting cancer patients, stool collection might take place after colonoscopy; endoscopic biopsy of polyps or cancers may cause bleeding and induce overestimation of sensitivity. Fourth, as FOBT aim at CRC detection, this study evaluated diagnostic performance of FOBTs for CRC detection only; detection of advanced adenoma was not performed in this meta-analysis. The stage of cancer affects the performance of FOBT; however, it was not well-documented in primary studies. Subgroup analysis of stage of cancer was not available; results in this meta-analysis do not reflect early stage disease. Finally, some unpublished studies may not have been identified through the literature search in OVID databases and publication bias may exist in this meta-analysis. Lastly, studies showed substantial heterogeneity.

In conclusion, this systematic review and meta-analysis showed that FOBT, both gFOBT and iFOBT, have a better diagnostic performance for the relative detection of CRC in the distal colon than that in the proximal colon.

The Use and Impact of QOL Assessment Tools in Clinical Care Settings for Cancer Patients....

open access:
The Use and Impact of Quality of Life Assessment Tools in Clinical Care Settings for Cancer Patients, with a Particular Emphasis on Brain Cancer: Insights from a Systematic Review and Stakeholder Consultations | RAND

Design

We conducted a systematic literature review, 15 expert interviews and a consultation at an international summit.

Results

The systematic review found no relevant intervention studies specifically in brain cancer patients, and after expanding our search to include other cancers, 15 relevant studies were identified. The evidence on the effectiveness of using QoL tools was inconsistent for patient management, but somewhat more consistent in favour of improving patient–physician communication. Interviews identified unharnessed potential and growing interest in QoL tool use and associated challenges to address.

Tubal ligation and incidence of 26 site-specific cancers in the Million Women Study

open access
British Journal of Cancer - Tubal ligation and incidence of 26 site-specific cancers in the Million Women Study

There were no significant associations between tubal ligation and risk of cancers at the other sites, including cancers of the endometrium, cervix, breast and colorectum.

We believe that this is the first study to report that tubal ligation is associated with a significant reduction in risk of fallopian tube cancer (Riska et al, 2007; Vicus et al, 2010).

The large size of the cohort, the individual information on possible confounding factors, and the complete and long follow-up, provided reliable estimates of risks associated with tubal ligation for 26 specific cancer sites, even relatively uncommon ones. We found no association between tubal ligation and the risk of cancers of the endometrium, breast, or cervix. By contrast, tubal ligation is associated with a clear reduction in risk of ovarian cancer, a reduction of similar magnitude of peritoneal cancer, and a reduction of fallopian tube cancer. That tubal ligation is associated with a reduced risk of cancers of the ovary, peritoneum and fallopian tube, but not of other hormonally-related cancers, is consistent with the hypothesis that many of the cancers at these sites have a shared origin in the fallopian tube, and that tubal ligation reduces cancer risk by acting as a barrier to cells, carcinogens or other agents reaching the ovary and peritoneal cavity, rather than by affecting hormone levels.

Aspirin in the Treatment of Cancer: Reductions in Metastatic Spread and in Mortality

open access
PLOS ONE: Aspirin in the Treatment of Cancer: Reductions in Metastatic Spread and in Mortality: A Systematic Review and Meta-Analyses of Published Studies

.... A mutation of PIK3CA was present in about 20% of patients, and appeared to explain most of the reduction in colon cancer mortality by aspirin. Data were not adequate to examine the importance of this or any other marker in the effect of aspirin in the other cancers. On bleeding attributable to aspirin two reports stated that there had been no side effect or bleeding attributable to aspirin. Authors on the other reports were written to and 21 replied stating that no data on bleeding were available.

Conclusions and Implications

The study highlights the need for randomised trials of aspirin treatment in a variety of cancers. While these are awaited there is an urgent need for evidence from observational studies of aspirin and the less common cancers, and for more evidence of the relevance of possible bio-markers of the aspirin effect on a wide variety of cancers. In the meantime it is urged that patients in whom a cancer is diagnosed should be given details of this research, together with its limitations, to enable each to make an informed decision as to whether or not to take low-dose aspirin.

Systematic Review Protocol Number

CRD42015014145

reference (1 reference to ovarian cancer - abstract):

54. Nagle CM, Ibiebele TI, DeFazio A, Protani MM, Webb PM. Australian Ovarian Cancer Study Group. (2015) Aspirin, nonaspirin non-steroidal anti-inflammatory drugs, acetaminophen and ovarian cancer survival. Cancer Epidemiol. 39(2):196–9. doi: 10.1016/j.canep.2014.12.010. Epub 2015 Feb 7. pmid:25666512

Associations did not differ by histologic subtype or stage at diagnosis.•Results provide no strong evidence that use of aspirin or NSAIDs are associated with improved survival

Tuesday, April 26, 2016

(2009) A Population-Based 5-Year Cohort Study Including All Cases of Epithelial Ovarian Cancer in Western Sweden: 10-Year Survival & Prognostic Factors

open access

open access: Characteristics of 10-year survivors of high-grade serous ovarian carcinoma

Blogger's Note: previously posted as abstract

open access

Highlights

•: Ovarian cancer survivors who live for 10 or more years comprise a heterogeneous patient population with and without recurrent disease.
•: Long-term survivors may have suboptimal cytoreduction or short platinum free intervals.
•: BRCA1 and BRCA2 germline mutations appear common among long-term survivors.

Objective

High-grade serous carcinoma (HGSC) generally presents at an advanced stage with poor long-term (LT) survival. Here we describe clinical features found in women surviving HGSC for ten or more years.

Methods

A multi-center research consortium was established between five participating academic centers. Patient selection criteria included high-grade serous ovarian, fallopian tube, or peritoneal carcinoma with at least ten years of follow up. Non-serous, borderline tumors and low-grade serous subtypes were excluded......

(Blogger Notes: some key items)

median age of 57 years (range 37–84 years)

All three patients with liver metastases remained progression free for more than 10 years and have not developed recurrence.

The median progression-free survival (PFS) of the entire cohort was 147 months. Twenty-one (11.2%) patients had one recurrence during the follow-up interval, 19 (10.1%) recurred twice, and 60 (31.9%) suffered from more than two recurrences, with 13 patients having more than 10 reported recurrences.

There were eight patients with stage IV disease who did not experience any recurrence of their disease after initial treatment.

Intended care seeking for ovarian cancer symptoms among U.S. women (also ref to UK...)

open access

Abstract

To investigate U.S. women's intended care seeking for symptoms associated with ovarian cancer, data from the 2012 HealthStyles Fall survey of U.S. adults were examined. Analyses were limited to women with no history of gynecologic cancer (N = 1726). Logistic regression models for intended care seeking within 2 weeks of symptom onset were developed. A minority of women recognized that unexplained pelvic or abdominal pain (29.9%), unexplained bloating (18.1%), and feeling full after eating a small amount of food (10.1%) can indicate ovarian cancer, and 31.1% mistakenly believed that the Papanicolaou (Pap) test screens for the disease. In the multivariate regression models, the most consistent, significant predictors (p < 0.01) of intended care seeking within 2 weeks of symptom onset were age (older women were more likely to seek care) and awareness that symptoms could signal ovarian cancer. Care seeking in response to ovarian cancer symptoms may be delayed among younger women and those who do not recognize the potential significance of symptoms. Raising awareness of ovarian cancer symptoms may promote early detection. However, educational efforts should emphasize that symptoms associated with ovarian cancer may also result from benign conditions.

Introduction

Ovarian cancer causes more deaths in the United States than any other cancer of the female reproductive system. Annually, more than 20,000 U.S. women are diagnosed with ovarian cancer and more than 14,000 die from the disease (U.S. Cancer Statistics Working Group, 2014). Treatment is most effective when ovarian cancer is found at an early stage. However, no population-based screening test is recommended for ovarian cancer detection, and most ovarian cancers are diagnosed at a late stage (Su et al., 2013).

While ovarian cancer has been widely referred to as a “silent killer,” symptoms commonly associated with the disease have been identified (Goff, 2012). Unfortunately, awareness of ovarian cancer symptoms among U.S. women is low....

eg. Unexplained bloating:

After several months		12.0%
I would probably not call or see a doctor		25.4%

Similarly, an analysis of UK women found low recognition of symptoms associated with ovarian cancer and variation in intention to seek care for these symptoms (Low et al., 2013). Conversely, in a study of Welsh women, ovarian cancer symptom awareness was not associated with delayed care seeking; however, respondents' awareness of ovarian cancer symptoms was much higher than in the current study (Brain et al., 2014).

The Beryl Institute - Improving the Patient Experience

The Beryl Institute
About
The Beryl Institute is the global community of practice dedicated to improving the patient experience through collaboration and shared knowledge. We define the patient experience as the sum of all interactions, shaped by an organization's culture, that influence patient perceptions across the continuum of care. READ MORE»

Publications

Read informative papers on key issues which are impacting the patient experience.

Case Studies

Discover proven practices being implemented to improve the patient experience.

Nonbleeding adenomas: Evidence of systematic false-negative fecal immunochemical test results and their implications for screening effectiveness

abstract:Nonbleeding adenomas: Evidence of systematic false-negative fecal immunochemical test results and their implications for screening effectiveness–A modeling study

BACKGROUND

If some adenomas do not bleed over several years, they will cause systematic false-negative fecal immunochemical test (FIT) results. The long-term effectiveness of FIT screening has been estimated without accounting for such systematic false-negativity. There are now data with which to evaluate this issue.

METHODS

The authors developed one microsimulation model (MISCAN [MIcrosimulation SCreening ANalysis]-Colon) without systematic false-negative FIT results and one model that allowed a percentage of adenomas to be systematically missed in successive FIT screening rounds. Both variants were adjusted to reproduce the first-round findings of the Dutch CORERO FIT screening trial. The authors then compared simulated detection rates in the second screening round with those observed, and adjusted the simulated percentage of systematically missed adenomas to those data. Finally, the authors calculated the impact of systematic false-negative FIT results on the effectiveness of repeated FIT screening.

RESULTS

The model without systematic false-negativity simulated higher detection rates in the second screening round than observed. These observed rates could be reproduced when assuming that FIT systematically missed 26% of advanced and 73% of nonadvanced adenomas. To reduce the false-positive rate in the second round to the observed level, the authors also had to assume that 30% of false-positive findings were systematically false-positive. Systematic false-negative FIT testing limits the long-term reduction of biennial FIT screening in the incidence of colorectal cancer (35.6% vs 40.9%) and its mortality (55.2% vs 59.0%) in participants.

CONCLUSIONS

The results of the current study provide convincing evidence based on the combination of real-life and modeling data that a percentage of adenomas are systematically missed by repeat FIT screening. This impairs the efficacy of FIT screening.

Institutional capacity to provide psychosocial oncology support services... Zebrack et al

abstract
Institutional capacity to provide psychosocial oncology support services: A report from the Association of Oncology Social Work

BACKGROUND

This study reports cancer-treating institutions' capacity to deliver comprehensive psychosocial support services.

METHODS

Oncology care providers at 60 cancer-treating institutions completed surveys assessing the capacity of their institutions to provide psychosocial care. Capacity was assessed with the Cancer Psychosocial Care Matrix (CPCM) from the National Cancer Institute (NCI). Scores represented individuals' perceptions of their cancer program's performance with respect to 10 fundamental elements of psychosocial care.

RESULTS

Among 2134 respondents, 62% reported a mid-level capacity for ≥5 of 10 CPCM items. In comparison with other types of cancer programs (eg, NCI-designated, academic, or comprehensive centers), providers at community cancer programs reported a significantly greater capacity with respect to patient-provider communication, psychosocial needs assessment, and continuity in the delivery of psychosocial care over time. Nurses and primary medical providers reported a significantly lower capacity for linking patients and families with needed psychosocial services within their respective cancer programs. They also reported a significantly higher capacity for conducting follow-up, re-evaluations, and adjustments of psychosocial treatment plans.

CONCLUSIONS

Cancer programs are performing moderately well in terms of communicating to patients the importance of psychosocial care, identifying patient psychosocial needs, and referring patients and families to psychosocial services. They are doing less well with respect to the provision of that care over time. Findings suggest that gaps in psychosocial service capacity are a function of patient, provider, and system characteristics. These results may be useful in formulating strategies to enhance psychosocial care delivery.

Quality of psychosocial services in cancer centers: Today and tomorrow

abstract (full access req's $$)

Data from Zebrack et al's survey of 57 cancer centers in the United States and Canada have led the authors to conclude that cancers centers are performing moderately well in communicating the importance of psychosocial care, identifying patient psychosocial needs, and referring patients to services. This editorial focuses on areas that need further work and places the data in the context of the process of changing practice to improve the quality of care

NYSEO1 immunotherapy for ovarian cancer (video 9 min) - Dr Kunhli Odunsi

ecancer.tv

Dr Kunhli Odunsi - Roswell Park, New York, USA

Dr Kunhli Odunsi talks to ecancertv at AACR2016 about his research into courses of immunotherapy against ovarian cancer.

Having established in previous research the link between T cell infiltration of a tumour to improved patient survival, Dr Odunsi has sought to determine an ovarian cancer antigen - in this case NYSEO1 - to prolong patient remission and promote anti-tumour immune response in patients.

Dietary fat intake and ovarian cancer risk: a meta-analysis of epidemiological studies

open access

Abstract

Observational studies assessing the association of dietary fat and risk of ovarian cancer yield discrepant results. Pertinent prospective cohort studies were identified by a PubMed search from inception to December 2015. Sixteen independent case-control and nine cohort studies on dietary fat intake were included, with approximately 900,000 subjects in total. Relative risks (RRs) with 95% confidence intervals were pooled using a random effects model. Heterogeneity, sensitivity analysis and publication bias were assessed; subgroup analysis and analysis stratified by EOC histology were conducted. The reported studies showed a significant increase of ovarian cancer risk with high consumption of total-, saturated-, and trans-fats, while serous ovarian cancer was more susceptible to dietary fat consumption than other pathological subtypes. No evidence of positive association between dietary fat intake and ovarian cancer risk was provided by cohort studies. Menopausal status, hormone replacement therapy, body mass index (BMI), and pregnancy times, modified the objective associations. In conclusion, the meta-analysis findings indicate that high consumption of total, saturated and trans-fats increase ovarian cancer risk, and different histological subtypes have different susceptibility to dietary fat.

Introduction

Ovarian cancer is considered the sixth most commonly diagnosed cancer among women and the second cause of gynecologic cancer mortality worldwide [1, 2]. The prognosis of ovarian cancer is poor, with the initial diagnosis in most patients made at an advanced stage [3, 4]. The noticeable relationship between ovarian cancer incidence and geographical regions suggested that dietary habits and ethnic variations are potentially modifiable factors [5], whose etiologic role in ovarian cancer risk, however, remains undefined [6].

Dietary fat, as one of the most controversial dietary factors in nutritional epidemiology, has been reported with positive correlations with breast [7] and gastric [8] cancers in two recent meta-analyses, and elevated ovarian cancer risk in early ecologic studies [5, 9]. Although multiple epidemiologic studies have explored the associations between dietary fat consumption and risk of ovarian cancer, no definite conclusion have been drawn, and the dietary fat varieties as well as pathological types of ovarian cancer increase the complexity of this research topic. The results of two meta-analyses [10, 11] and a pooled analysis [12] that included data from 12 cohort studies also reached inconsistent conclusions. Therefore, we conducted a meta-analysis of case-control and cohort studies with more-detailed analyses of 1) the epidemiologic evidence regarding the association of dietary fat consumption with risk of ovarian cancer, 2) the association between dietary fat intake and the risk of ovarian cancer and pathological subtypes. This analysis was based on dietary fat types, and we extended the previous analyses [10, 11] with more included studies and dietary fat types, and an assessment stratified by EOC histology.

Materials and Methods

Search strategy

We obtained the literature published in any language to December 2015 by fully searching the PubMed database. The search terms used were “diet”, ‘‘dietary fat’’ in combination with “ovarian cancer,” “ovarian neoplasm” or “ovarian carcinoma”, without restrictions. In addition, we reviewed the reference lists of retrieved studies and recent reviews to supplement electronic database searches......

An important highlight of our meta-analysis is that we analyzed the association between dietary fat intake and the risk of ovarian cancer subtypes. We found that serous ovarian cancer incidence was more susceptible to dietary fat intake. However, these results should be interpreted with caution. The insufficient number of included cases and potential misclassification of pathological subtypes may contribute to the statistical difference observed.

Future studies should focus more on specific pathological subtypes of ovarian cancer as well as the influence of molecular mechanisms and genetic factors on the association of dietary fat and ovarian cancer.

"Cancer Moonshot" could push open-access frontiers

News

Astra Zeneca announces new genomics research centre

PHG Foundation news

Most Americans Turn to Prayer for Healing, Survey Finds

Survey Finds

What I know now... World Ovarian Cancer Day - what message would you share (share on Target Ovarian website)

Target Ovarian Cancer

Posted by Target Ovarian Cancer on Monday 25 April 2016

Target Ovarian Cancer works across the UK to support people who are affected by ovarian cancer. Every year on 8 May we join forces worldwide for World Ovarian Cancer Day to create a global conversation and support a quarter of a million people who are diagnosed each year.

This year we’re talking about “What I know now…” and sharing words of advice, guidance and even cautionary tales that we’ve built up over the years to answer the question: ‘If you knew then what you know now, what message would you share?’

Investigation of Exomic Variants Associated with Overall Survival in Ovarian Cancer

open access (technical)

Background: While numerous susceptibility loci for epithelial ovarian cancer (EOC) have been identified, few associations have been reported with overall survival. In the absence of common prognostic genetic markers, we hypothesize that rare coding variants may be associated with overall EOC survival and assessed their contribution in two exome-based genotyping projects of the Ovarian Cancer Association Consortium (OCAC).
Conclusions: Common variant rs8170 and rare variants in ATG2B may be associated with EOC overall survival, although further study is needed.
Impact: This study represents the first exome-wide association study of EOC survival to include rare variant analyses, and suggests that complementary single variant and gene-level analyses in large studies are needed to identify rare variants that warrant follow-up study. Cancer Epidemiol Biomarkers Prev; 25(3); 446–54. ©2016 AACR.

Researchers push for personalized tumour vaccines : Nature News & Comment

personalized tumour vaccines

High Efficacy and Low Toxicity of the Modified Docetaxel and Carboplatin Protocol in Patients with Recurrent Ovarian Cancer—A Phase 2 Cohort Study

open access

Objective: Most patients with epithelial ovarian cancer will experience a recurrence; currently, there is no cure. In patients with platinum-sensitive disease (platinum-free interval >6 months), a combination similar to that used as frontline therapy (carboplatin and paclitaxel) is recommended. However, it is associated with a high incidence (20%) of neurotoxicity. This study evaluated the efficacy and toxicity of combination docetaxel/carboplatin therapy in patients with platinum-sensitive recurrent ovarian cancer.

Methods: Forty patients with recurrent, histologically proven ovarian, fallopian tube, or primary peritoneal cancer were enrolled in this phase 2 trial. The study protocol included combination therapy with docetaxel, 30 mg/m², on days 1 and 8, and carboplatin, area under the curve 5, on day 1, every 21 days. Twenty received the classical paclitaxel/carboplatin regimen (control group), and another 20 received the modified docetaxel/carboplatin protocol (study group).

Results: Median follow-up was 78 months for the study group and 62 months for the control group. The study group had a higher overall response rate compared to controls: 80% and 30%, respectively (P = 0.004; relative risk, 9.3; 95% confidence interval, 2.18–39.96). Complete response was achieved in 60% and 25%, respectively (P = 0.054). The study group patients showed a superior 2-year survival rate of 75% compared with the 35% of the controls (P = 0.011; relative risk, 5.57; 95% confidence interval, 1.47–21.56). Hematological and neurological toxicity rates did not differ between the groups (P = 0.451 and P = 0.605, respectively).

Conclusions: Patients with recurrent ovarian cancer who received the modified docetaxel/carboplatin regimen had higher overall response and survival rates compared to those who had the paclitaxel/carboplatin regimen, with no difference in toxicity. Future larger studies should focus on strategies to compare this regimen to the current standard, with an emphasis on quality of life.

Ovarian cancer is the most common cause of death among women with gynecological malignancies.¹ Most patients with epithelial ovarian cancer have a satisfactory initial clinical response to aggressive cytoreductive surgery followed by combination chemotherapy; however, unfortunately, this usually does not lead to cure. Most patients (>80%) will experience a recurrence.²

At present, randomized studies support the use of single-agent chemotherapy for recurrent platinum-resistant ovarian cancer (platinum-free interval ≤6 months). Although combination therapies are associated with somewhat higher response rates, they are more toxic, and no regimen has produced a survival benefit compared to single-agent treatment.^3....

COX-1 Inhibitors: Beyond Structure Toward Therapy

abstract

Biosynthesis of prostaglandins from arachidonic acid (AA) is catalyzed by cyclooxygenase (COX), which exists as COX-1 and COX-2. AA is in turn released from the cell membrane upon neopathological stimuli. COX inhibitors interfere in this catalytic and disease onset process. The recent prominent discovery involvements of COX-1 are mainly in cancer and inflammation. Five classes of COX-1 inhibitors are known up to now and this classification is based on chemical features of both synthetic compounds and substances from natural sources. Physicochemical interactions identification between such molecules and COX-1 active site was achieved through X-ray, mutagenesis experiments, specific assays and docking investigations, as well as through a pharmacometric predictive model building. All these insights allowed the design of new highly selective COX-1 inhibitors to be tested into those disease models in which COX-1 is involved. Particularly, COX-1 is expressed at high levels in the early to advanced stages of human epithelial ovarian cancer, and it also seems to play a pivotal role in cancer progression. The refinement of COX-1 selective inhibitor structure has progressed to the stage that some of the inhibitors described in this review could be considered as promising active principle ingredients of drugs and hence part of specific therapeutic protocols. This review aims to outline achievements, in the last 5 years, dealing with the identification of highly selective synthetic and from plant extracts COX-1 inhibitors and their theranostic use in neuroinflammation and ovarian cancer. Their gastrotoxic effect is also discussed.

What made HIPEC an effective curative treatment for peritoneal surface malignancy: A 25-year experience with 1,125 procedures

What made hyperthermic intraperitoneal chemotherapy an effective curative treatment for peritoneal surface malignancy: A 25-year experience with 1,125 procedures

Objective

To review our 25-year experience with hyperthermic intra-peritoneal chemotherapy (HIPEC).

Background

Combining cytoreductive surgery (CRS) and HIPEC as local treatments for peritoneal carcinomatosis (PC) was proposed 25 years ago.

Methods

A prospective database of all patients undergoing HIPEC for PC since 1989 was searched for clinicopathological data, 90-day morbidity and mortality, and survival.

Results

Among 1,125 HIPEC procedures, PC origin was colorectal (342; 30%), ovarian (271; 24%), pseudomyxoma peritonei (189; 17%), gastric (127; 11%), malignant mesothelioma (84; 8%), or other (112; 10%). Between 2004–2009 (n = 321) and 2010–2015 (n = 560), the median peritoneal cancer index decreased (11 vs. 8; P < 0.001), fewer patients underwent incomplete cytoreduction (CC2-3: 4% vs. 0.5%; P < 0.001), and more were included in randomized trials (5% vs. 16%; P < 0.001). Postoperative morbidity (52% vs. 50%, P = 0.672) was not different, but mortality significantly decreased (5% vs. 2%; P = 0.030). Median overall-survival was 42 months, and improved significantly for each 5-year period except for 2006–2010 vs. 2011–2015 (P = 0.097). The 10-year survival without recurrence was 53%, 14%, 4%, 10%, and 9% for pseudomyxoma, mesothelioma, ovarian, colorectal, and gastric PC, respectively.

Conclusion

This study demonstrated that CRS and HIPEC provide long-term survival irrespective of PC origin, and survival improves with experience. J. Surg. Oncol.

Immune Checkpoint Inhibitors in the Treatment of Gynecologic Malignancies

abstract

There is mounting evidence that the immune system plays an important role in the development and growth of gynecologic malignancies, and preliminary studies show activity of immune checkpoint inhibitors in ovarian, endometrial, and cervix cancer. In this review, we outline the completed trials of immune checkpoint blockade in the treatment of gynecologic malignancies. In addition, we review the ongoing trials in each disease site. The questions of which patients will benefit from immune checkpoint inhibitors and when immune checkpoint inhibitors should be incorporated into the treatment of gynecologic malignancies continue to be largely unanswered. As preclinical and clinical data emerge regarding predictive markers for response and resistance to immune checkpoint inhibitors, rational combination treatment strategies will help to further develop this emerging field in the treatment of gynecologic malignancies.

Hereditary Colorectal Cancer Syndromes: ASCO Clinical Practice Guideline Endorsement of the Familial Risk–Colorectal Cancer: ESMO Clinical Practice Guidelines

Blogger's Note: excerpt below as it applies to CA125/extracolonic surveillance

open access
Hereditary Colorectal Cancer Syndromes: American Society of Clinical Oncology Clinical Practice Guideline Endorsement of the Familial Risk–Colorectal Cancer: European Society for Medical Oncology Clinical Practice Guidelines http://ovariancancerandus.blogspot.com/feeds/posts/default

ASCO Surveillance Recommendations

ESMO recommendations, with original language, are listed below with qualifying statements added by the ASCO Endorsement Panel listed in bold italics (Data Supplement 2 provides ESMO recommendations, reprinted with permission).¹

Lynch syndrome

Colon and rectum: Colonoscopy every 1 to 2 years, starting at age 20 to 25 or 5 years before the youngest case in the family. No upper limit is established.
Endometrium and ovary: Gynecological examination, pelvic ultrasound (not CA-125), and aspiration biopsy every year, from age 30 to 35 years. Consider prophylactic hysterectomy and salpingoophorectomy when childbearing is completed.
Gastric cancer: For gastric cancer, the search for the presence of Helicobacter pylori and subsequent eradication is recommended in mutation carriers. In case of a high incidence of gastric cancer in some populations, some experts recommend upper GI endoscopy every 1 to 3 years.
Other Lynch-associated cancers: Surveillance is not recommended due to the low sensitivity and specificity. (Although there are insufficient data supporting surveillance for other target organs, it may be considered in the context of family history.)

Additional Resources

The fully published guideline² and more information, including Data Supplements (with reprinted ESMO recommendations and diagnosis algorithms), a Methodology Supplement, slide sets, and clinical tools and resources, are available at www.asco.org/endorsements/HereditaryCRC. Patient information is available at www.cancer.net.

Monday, April 25, 2016

Power of positive thinking skews mindfulness studies

Nature News & Comment

This doesn’t necessarily suggest that none of the mindfulness treatments work, says study co-author Brett Thombs, a psychologist at McGill and at the Jewish General Hospital in Montreal. “I have no doubt that mindfulness helps a lot of people,” he says. “I’m not against mindfulness. I think that we need to have honestly and completely reported evidence to figure out for whom it works and how much.”

The bias towards reporting positive results is pervasive across many types of mental health, psychology and medical research, says Ferguson. For example, the widely popularized theory of ego depletion — that people have limited self-control for decisions — recently failed to hold up in a large replication trial. “A lot of these things are reported to be true, they’re in a TEDx talk,” he says. “Now we're seeing, when we look at things much more closely, we’ve kind of been bullshitting people [for] a decade.”

Chemoprevention of hereditary colon cancers: time for new strategies

abstract

Colorectal cancer (CRC) is potentially preventable. Chemoprevention, a focus of research for the past three decades, aims to prevent or delay the onset of cancer through the regression or prevention of colonic adenomas. Ideal pharmacological agents for chemoprevention should be cheap and nontoxic. Although data indicate that aspirin can reduce the risk of CRC in the general population, the highest return from chemopreventive strategies would be expected in patients with the highest risk of developing the disease, particularly those with a defined hereditary predisposition. Despite compelling data showing that a large number of chemopreventive agents show promise in preclinical CRC models, clinical studies have yielded conflicting results. This Review provides a historical and methodological perspective of chemoprevention in familial adenomatous polyposis and Lynch syndrome, and summarizes the current status of CRC chemoprevention in humans. Our goal is to critically focus on important issues of trial design, with particular attention on the choice of appropriate trial end points, how such end points should be measured, and which patients are the ideal candidates to be included in a chemopreventive trial.

Non-surgical management of ovarian cancer: Prevalence and implications

abstract

PURPOSE:

To identify prevalence, correlates and survival implications of non-surgically managed epithelial ovarian cancer (EOC).

METHODS:

The National Cancer Database (NCDB) was queried for EOC cases between 2003 and 2011. Type of treatment, survival data, reasons for non-surgical treatment, clinicopathologic and process-based factors were collected. Logistic regression identified independent predictors of surgical treatment; Cox proportional hazards regression modeled association between time to death and receipt of surgery.

RESULTS:

172,687 of 210,667 patients (82%) received surgical treatment for EOC. 95% of patients treated non-surgically had stage III, stage IV or unknown stage disease. The reason for non-surgical treatment was unclear in 80% of cases. Black race and uninsurance were significantly associated with non-surgical treatment. Median survival time was 57.4months (95% CI: 56.8-57.9) for surgery with or without systemic treatment compared to 11.9months (95% CI: 11.6-12.2) for systemic treatment alone and 1.4months (95% CI: 1.3-1.4) for no treatment. Relative to surgical treatment, the adjusted hazard ratio for death associated with systemic treatment alone was 1.9 (p<0.001); hazard ratio for untreated patients was 4.7 (p<0.001). Among 29,921 patients older than 75 with Stage III/IV disease, 21.5% received only systemic treatment; 22.8% were entirely untreated.

CONCLUSION:

18% of EOC patients in the NCDB did not receive surgical treatment. These patients experienced significantly worsened survival. Prospective investigation is needed to determine how often apparent deviation from best-practices guidelines is clinically appropriate. Non-surgically treated patients may be at risk for poor access to gynecologic oncology care and deserve further study.