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Tuesday, July 28, 2015

Vitamin D and Cancer: Diversity, Complexity, and Still a Ways to Go



 http://cancerpreventionresearch.aacrjournals.org/content/vol8/issue7/home_cover.gif

abstract

 Vitamin D has taken a center-stage role in our basic and population research quest for the panacea for all human maladies, including cancer, yet sufficient evidence for a beneficial role has existed only for bone health. This Commentary discusses and places into a broader context the report of Chandler and colleagues that found a protective association for higher vitamin D status in colorectal cancer in women, consistent with most other cohort studies but not with limited supplementation trial data. Little human evidence exists for the preventive potential in other malignancies, including breast cancer, with the exception of possible benefit in bladder cancer and an adverse serologic association with prostate cancer (pancreatic cancer risk may be similarly influenced) that is supported by vitamin D genetic data. Current vitamin D trials are examining high-dose supplementation (i.e., 1,600–3,333 IU daily) for effects on multiple outcomes, but they may not have sufficient power to test efficacy in colorectal or other specific malignancies and are unlikely to inform any benefit for higher physiologic levels. A more complete understanding of vitamin D and human carcinogenesis will come from multifaceted lines of research, including elucidation of organ site–specific biologic mechanisms, prospective serologic analyses, testing of vitamin D–related genetic variation, and short-term clinical–metabolic biomarker studies of multidose vitamin D supplementation, including metabolomic profiling of controlled supplementation in these and past or ongoing trials. Cancer Prev Res; 8(8); 1–5. ©2015 AACR.

 See related article by Chandler et al., p. 675
 

European Union Bans Hundreds of Drugs Over Clinical Trial Studies



media

Canada Takes Long to Approve New Drugs - and That's Good 



media

CMAJl: Need to define patient engagement in research



article

Initial assessment of patient handoff in accredited general surgery residency programs in the U.S. & Canada



 Can J Surg, Vol. 58, No. 4, August 2015

....our study was restricted to junior surgical residents and did not include senior
level residents, which may overstate the lack the training and/or inexperience with handoffs.....

open access: Initial assessment of patient handoff in accredited
general surgery residency programs in the United States and Canada: a cross-sectional survey

 .....Of the American residents, 67% and 6% reported receiving an incomplete handoff that resulted in minor and major patient harm, respectively. These results mirrored those from Canadian reidents (63% minor and 7% major harm). The most frequent factor reported to improve the patient handoff process was standardization of the verbal handoff.....
 
Conclusion:
Our survey results indicate that the current patient handoff system con
tributes to patient harm. More efforts are needed to establish standardized forms of
verbal and written handoff to ensure patient safety and continuity of c

1 in 3 Patients With Cancer Meets the Criteria for Mental Disorders: What Does That Mean?



Blogger's Note: gynecologic cancers were grouped together in the original study

Correspondence (open access)

Author's Response (open access) (to Correspondence above)

open access: link to original article
 Four-Week Prevalence of Mental Disorders in Patients With Cancer Across Major Tumor Entities


Four challenges we have to crack before immune therapy can revolutionize how we fight cancer



The Conversation (blog)
 Author 
Sri Krishna PhD Candidate, Biological Design, School of Biological and Health Systems Engineering at Arizona State University

Most of us know about the conventional treatment of cancer: surgery to remove tumors, chemotherapy and radiation. But within the last five years, a new class of drugs that use our immune systems to fight cancer are gaining traction in cancer treatment. This is called “immunotherapy.” Instead of killing cancer cells with radiation or chemotherapy, immunotherapy mobilizes the immune system to fight against cancer much like it does against bacteria and viruses.
For a training immunologist like myself, immune therapies have opened new doors to understanding and treating cancers. In the future, immunotherapy could mean a personalized treatment, entirely tailored to an individual. As exciting as that sounds, we still have plenty of work to do, as there remains a lot we don’t know about the immune system. Here are some of the challenges we need to overcome to create these personalized treatments......

FDA Alert: Gadolinium-based Contrast Agents for MRI: Drug Safety Communication - FDA Evaluating



FDA Alert

 July 27, 2015
Audience: Radiology

ISSUE: FDA is investigating the risk of brain deposits following repeated use of gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI). Recent publications in the medical literature have reported that deposits of GBCAs remain in the brains of some patients who undergo four or more contrast MRI scans, long after the last administration. It is unknown whether these gadolinium deposits are harmful or can lead to adverse health effects.
FDA, including its National Center for Toxicological Research (NCTR), will study this possible safety risk further. FDA is working with the research community and industry to understand the mechanism of gadolinium retention and to determine if there are any potential adverse health effects. Based on the need for additional information, at this time, FDA is not requiring manufacturers to make changes to the labels of GBCA products.

Monday, July 27, 2015

Management of Patients With a Genetic Variant of Unknown Significance



Medscape

Industry influences osteoporosis treatment - without evidence (vitamin D/calcium)



Healthnewsreview

Pragmatic Randomized Trials Without Standard Informed Consent?



Abstract

Pragmatic Randomized Trials Without Standard Informed Consent?: A National SurveyPragmatic Randomized Trials Without Standard Informed Consent? | Annals of Internal Medicine


Background: Significant debate surrounds the issue of whether written consent is necessary for pragmatic randomized, controlled trials (RCTs) with low risk.
Objective: To assess the U.S. public's views on alternatives to written consent for low-risk pragmatic RCTs.
Design: National experimental survey (2 × 2 factorial design) examining support for written consent versus general notification or verbal consent in 2 research scenarios.
Setting: Web-based survey conducted in December 2014.
Participants: 2130 U.S. adults sampled from a nationally representative, probability-based online panel (response rate, 64.0%).
Measurements: Respondent's recommendation to an ethics review board and personal preference as a potential participant for how to obtain consent or notification in the 2 research scenarios.
Results: A majority of respondents in each of the 4 groups (range, 60.3% to 71.5%) recommended written informed consent, and personal preferences were generally in line with that advice. Most (78.9%) believed that the pragmatic RCTs did not pose additional risks, but 62.5% of these respondents would still recommend written consent. In contrast, a substantial minority in all groups (28.5% to 39.7%) recommended the alternative option (general notification or verbal consent) over written consent.
Limitation: Framing effects could have impacted respondents' attitudes, and nonrespondents may have differed in levels of trust toward research or health care institutions.
Conclusion: A majority of the public favored written informed consent over the most widely advocated alternatives for low-risk pragmatic RCTs; however, a substantial minority favored general notification or verbal consent.

Ovarian vein thrombosis after debulking surgery for ovarian cancer: epidemiology and clinical significance



abstract

Objective

Ovarian vein thrombosis is associated with pregnancy and pelvic surgery. Postpartum ovarian vein thrombosis is associated with infection and a high morbidity rate and is treated with anticoagulant and intravenous antibiotic therapy. The natural history of such thrombotic events after debulking surgery for ovarian cancer has not been well described. Our objective was to characterize the presentation and outcomes for patients with this condition at our institution.

Study Design

We conducted a retrospective study of patients who underwent surgical debulking for ovarian cancer at Memorial Sloan Kettering Cancer Center between the years 2001 and 2010. Patients were included if contrast computed tomography scans of both the abdomen and pelvis were performed within 12 weeks before and 12 weeks after the surgery. The images were reviewed to assess for the presence and extent of a new postoperative ovarian vein thrombosis. When available, subsequent studies were assessed for thrombus progression. Medical records were reviewed to determine whether anticoagulation was used for treatment of the thrombotic episode and to record the occurrence of any new significant venous thromboembolic event in the next year.

Results

One hundred fifty-nine patients had satisfactory imaging. New ovarian vein thrombosis was a common complication of debulking surgery, as found in 41 of patients (25.8%). Only 5 women with ovarian vein thrombosis were started on anticoagulation, of which 2 individuals had an independent venous thromboembolic event as indication for treatment. Only 2 of the ovarian vein thromboses (4.9%) progressed to the inferior vena cava or left renal vein on subsequent scan. The estimated cumulative incidence of venous thromboembolism 1 year after the first postoperative scan was 17.1% for patients in the new ovarian vein thrombosis group vs 15.3% of individuals for the group without a postoperative ovarian vein thrombosis (P = .78).

Conclusion

Ovarian vein thrombosis is commonly encountered after debulking surgery for ovarian cancer. Anticoagulation is usually not indicated, and clinically meaningful thrombus progression rarely occurs.

Identifying novel hypoxia-associated markers of chemoresistance in ovarian cancer



open access
 

Conclusions

Overall, these results show that the most important determining factor for development of resistance is the presence of hypoxia during the treatment period, not prior to treatment thus highlighting the potential importance of simultaneously reducing tumour hypoxia and treating with chemotherapy. This may have particular importance in patients with large tumours who receive neoadjuvant chemotherapy. A number of pathways are responsible for the resistance to cisplatin observed due to hypoxia, and that there are many candidate biomarkers of hypoxia which could be explored in the context of ovarian cancer. We have also provided an initial validation of selected hypoxia-associated biomarkers in ovarian tumour samples. It will be important to expand the study and to validate these results at the protein level in future studies in order to elucidate their true importance.

Sunday, July 26, 2015

The role of diagnostic ureteroscopy in the era of computed tomography urography



 Blogger's Note: of interest to Lynch Syndrome patients

open access 
 

Background

Upper urinary tract urothelial carcinoma (UTUC) is an uncommon malignancy, accounting for ~5 % of urothelial tumors [1]. The diagnosis of UTUC can be challenging, requiring a combination of radiographic, cytologic and endoscopic means. Time honored radiological tools such as intravenous urography and retrograde uretropyelograpy are currently replaced by modern computerized tomography urography (CTU) [2]. Diagnostic ureteroscopy is often performed following CTU. Flexible ureteroscopy allows exploration of the upper urinary tract and is beneficial when diagnostic uncertainty exists. It has the advantages of offering direct view of the tumor, ruling out other pathologies and achieving tissue diagnosis. Although nephrouereterectomy is considered the gold standard treatment of UTUC, endoscopic ablation and resection of the tumor can be successfully utilized in selected cases based on tumor size and histology, as determined during ureteroscopoy.......

Late Breaking Abstracts deadline notice: ECCO/ESMO 2015



Late Breaking Abstracts Deadine Dates
 The European Cancer Congress 2015
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Abstract submission open: 22 July 2015
Abstract submission deadline: 5 August 2015, 21:00 Central European time

Tea consumption and the incidence of cancer: a systematic review



abstract

The aim of this study was to summarize the current evidence on the strength of associations between tea consumption and the incidence of cancer at different sites. We searched PubMed, Embase and the Cochrane Library for relevant articles published before October 2013. Prospective studies that reported effect estimates of cancer incidence, with 95% confidence intervals (CIs), for more than two categories of tea consumption were included. We analysed 87 datasets (57 articles), which included a total of 49 812 incident cases. Overall, high tea consumption had no significant effect on the risk of gastric, rectal, colon, lung, pancreatic, liver, breast, prostate, ovarian, bladder cancers or gliomas. However, high tea consumption was associated with a reduced risk of oral cancer (risk ratio 0.72; 95% CI 0.54–0.95; P=0.021). A dose–response meta-analysis suggested that an increase in tea consumption by one cup per day was associated with a reduced risk of oral cancer (risk ratio 0.89; 95% CI 0.80–0.98; P=0.022), but had little effect on the incidence of other cancers. Subgroup analysis indicated that an increase in the consumption of black tea by one cup per day was associated with an increased risk of breast cancer. Moreover, in western countries, we found that an increase in the consumption of tea by one cup per day was associated with a reduced risk of bladder cancer. Increased tea consumption has no significant effect on the risk of common malignancies. For some cancer types, associations differ according to sex, ethnicity and tea type.

Saturday, July 25, 2015

Blog Archive: OvarianCancerandUs (see right hand column)





blog page views to date: 672,234

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An overview of early investigational therapies for chemoresistant ovarian cancer



Abstract

 INTRODUCTION:
Epithelial ovarian cancer (EOC) is the fourth commonest cause of female cancer death in the developed world. Although progress in treatment has improved survival, ∼ 80% of patients with advanced EOC will experience a recurrence and eventually will become resistant to chemotherapy. The aim of treatment for chemoresistant EOC has traditionally been limited to palliation of symptoms but the recent introduction of new therapies targeting molecular pathways is beginning to demonstrate improvements in disease control.

Areas covered:
This review provides an overview of early investigational drugs for the treatment of 'platinum-resistant' EOC. The article is based on English peer-reviewed articles located on MEDLINE and related abstracts presented at major international meetings.

Expert opinion:
Drugs targeting several pathways are increasingly used to treat 'platinum-resistant' EOC. Currently, drugs targeting the angiogenesis pathway have been shown to significantly improve patient outcome. Studies are also being undertaken with inhibitors of poly(ADP-ribose) polymerase (PARP), targeting the DNA repair pathway as it is possible that the benefits seen with these agents in 'platinum-sensitive' disease will apply to those with 'platinum-resistant' disease. The discovery of predictive biomarkers that identify patients which benefit from these targeted therapies is paramount to the success of these treatments in the future.

LIFE AND DEATH CAN BE STRONG MOTIVATION media (ovarian cancer....)



media
 
Rule No. 218 is “Grand passion will take you further than good grades,” and nothing focuses a passion more than when a problem is directly connected to your own life, as in living or dying.
Meet Laura Shawver. At the age of 49 in 2006, she was diagnosed with clear cell ovarian cancer. After getting the diagnosis, she was first surprised, then shocked and finally angry to learn that doctors had no idea what treatment to recommend for her particular case. This disease did not know who it was dealing with. Shawver was not your typical patient.
First, she has a Ph.D. in pharmacology, and second, she is relentless. She knew that a molecular profile of her tumor would help in determining the options, and she was upset that she could not easily get this done for ovarian cancer, even though it was being done regularly for patients with breast, lung and colon cancers......

Friday, July 24, 2015

Sweet and Vicious: Sugar and Sugar Substitutes



CureToday article


Sugar does not feed cancer cells any differently than it feeds healthy cells. - See more at: http://www.curetoday.com/community/amanda-bontempo/2015/07/sweet-and-vicious-sugar-and-sugar-substitutes?utm_source=Informz&utm_medium=Cure+Today&utm_campaign=CURExtra%2Demail%2DIncyte%2DJakafi%2D7%2D24%2D15#sthash.0JDxNJwB.dpuf
Sugar does not feed cancer cells any differently than it feeds healthy cells. - See more at: http://www.curetoday.com/community/amanda-bontempo/2015/07/sweet-and-vicious-sugar-and-sugar-substitutes?utm_source=Informz&utm_medium=Cure+Today&utm_campaign=CURExtra%2Demail%2DIncyte%2DJakafi%2D7%2D24%2D15#sthash.0JDxNJwB.dpuf
 Sugar does not feed cancer cells any differently than it feeds healthy cells......

Thesis: Drugs with potential chemopreventive properties in relation to epithelial ovarian cancer



pdf file Danish Medical Journal

 Drugs with potential chemopreventive properties in relation to epithelial ovarian cancer –a nationwide case-control study (note: includes section on statins)

......The results of this PhD thesis add important knowledge to the
area of chemoprevention in relation to epithelial ovarian cancer......

Impact of statins on risk and survival of ovarian cancer



KoreaMed Synapse

 J Gynecol Oncol. 2015 Jul;26(3):240-241. English.
Published online July 08, 2015.  http://dx.doi.org/10.3802/jgo.2015.26.3.240
Copyright © 2015. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

 Table 1. Summary of the evidence regarding impact of statin therapy on risk and survival of ovarian cancer

.....When findings of five studies [8, 10, 11, 12, 13] were pooled in a meta-analysis conducted by Liu et al. [14], a significant 21% risk reduction was seen (relative risk [RR], 0.79; 95% confidence interval [CI], 0.64 to 0.98). The RR reduction was found to be 52% when long term statin usage was considered (RR, 0.48; 95% CI, 0.28 to 0.80). In conclusion, we suggest that statins impact on ovarian cancer warrants further investigation with larger randomized controlled trials as observational studies are subject to bias and may lead to false slight benefits. Effect of statins with respect to different histological subtypes also need to be further studied.

Important molecule in ovarian cancer: (LKB1) Molecule plays pivotal role in making ovarian cancer cells so lethal



science news

....... Recently, Dr. Shepherds' lab discovered that the spheroids activate a 'stress signal', and the major molecule controlling this signal is called LKB1. "Previous studies stated that LKB1 was a tumour suppressor in ovarian cancer, meaning that tumour cells need to get rid of LKB1 to cause cancer," says Dr. Shepherd "but our work is in direct conflict with these studies, because we definitively show that ovarian cancer cells still have LKB1 and that this molecule allows ovarian cancer spheroids to change their metabolism, promote tumour cell survival and make them more resistant to chemotherapy."
By refuting these previous studies, Dr. Shepherd has uncovered a new target for future therapy. "There are currently no therapies or drugs that target LKB1," states Dr. Shepherd. "Based on these findings our lab is exploring several different strategies to understand and target LKB1 and its related molecules in ovarian cancer spheroids, and developing the essential pre-clinical models to see if this can be translated to ovarian cancer patients."

Story Source:
The above post is reprinted from materials provided by Lawson Health Research Institute.

Update: AllTrials – Pharma company investors call for clinical trials transparency



AllTrials


Read more in the Financial Times(£) and at Wall Street Journal.
Read today’s Economist editorial “The evidence base for new medicines is flawed. Time to fix it” and their longer piece “Spilling the beans. Failure to publish the results of all clinical trials is skewing medical science.“(http://www.alltrials.net/wp-content/uploads/2014/03/alltrials_basic_logo2.png

The Art of the Second Opinion



Cancer Network

‘Zombie report’ on health-care innovation in Canada gets new life (maybe)



media

In Support of a Patient-Driven Initiative and Petition to Lower the High Price of Cancer Drugs - Mayo Clinic



open access

 ....A cancer patient–based grassroots movement that advocates against the high price of cancer drugs can accomplish a great deal. One such movement, a petition, is already available and is actively collecting signees. It has been designed to be signed online on Change.org (short link URL: http://chn.ge/1DCWT1M) and is publicized on e-mail (stophighdrugcosts@gmail.com), on Facebook (https://www.facebook.com/stophighdrugcosts), and on Twitter (@StopHighRxCosts), thus using contemporary methods to address a contemporary crisis. Those encouraged to sign the petition include patients, relatives, friends, supporters, health care professionals, and others. Should this petition or any other similar grassroots efforts generate in aggregate an immense number of unique supporters (eg, >1 million petition signees or a comparable mass action quantified in other terms), this quantified support can then be used by advocates, lobbyists, and others to advocate against the aforementioned harms generated by the high price of cancer drugs. With proper support of these grassroots efforts, and proper use of that support downstream, it should be possible to focus the attention of pharmaceutical companies on this problem and to encourage our elected representatives to more effectively advocate for the interests of their most important constituents among the stakeholders in cancer—American cancer patients.

Systematic review of the relationship between artificial sweetener consumption and cancer in humans: analysis of 599,741 participants



abstract 

BACKGROUND:

The effect of artificial sweetener consumption on cancer risk has been debated in animal models for over four decades. To further investigate this relationship, this study aims to synthesise results from several of the most recent studies in humans.

METHODS:

An online literature search was performed in MEDLINE from 2003 to 2014 using Ovid, PubMed, Web of Science, and Scopus using keywords 'artificial', 'sweetener' and 'cancer'. Ninety-two results were then manually assessed for eligibility. Studies were included if the relationship between artificial sweeteners and cancer was their central hypothesis, and if they adjusted for age, gender, smoking status and body mass index. Extracted data included study design, patient characteristics, outcome measure and results.

RESULTS:

In the five publications that satisfied the inclusion criteria, significant direct associations with artificial consumption were found for laryngeal (odds ratio, OR 2.34, 95% CI: 1.20-4.55), urinary tract tumours (OR 2.12, 95% CI: 1.22-3.89), non-Hodgkin lymphoma in men (RR 1.31, 95% CI: 1.01-1.72), multiple myeloma in men (RR 2.02, 95% CI: 1.20-3.40) and leukaemia (RR 1.42, 95% CI: 1.00-2.02). Inverse relationships were found in breast (OR 0.70, 95% CI: 0.54-0.91, p trend = 0.015) and ovarian (OR 0.56, 95% CI: 0.38-0.81, p trend < 0.001) cancers.

CONCLUSION:

The statistical value of this review is limited by the heterogeneity and observational designs of the included studies. Although there is limited evidence to suggest that heavy consumption may increase the risk of certain cancers, overall the data presented are inconclusive as to any relationship between artificial sweeteners and cancer.

Intraoperative Adverse Events: Risk Adjustment for Procedure Complexity and Presence of Adhesions Is Crucial



abstract





Background

Benchmarking the quality of intraoperative care by comparing the rates of intraoperative adverse events (iAEs) necessitates adequate risk adjustment. We sought to identify the patient- and procedure-related risk factors for iAEs.

Study Design

Our 2007 to 2012 institutional American College of Surgeons NSQIP and administrative databases were linked and then screened for iAEs using the Patient Safety Indicator “Accidental Puncture/Laceration.” Intraoperative adverse events were confirmed by systematic review of medical records. Comorbidities were assessed using American College of Surgeons NSQIP variables. Adhesiolysis was determined using CPT codes for lysis of adhesions. Operative complexity was determined using relative value units. Multivariable models were constructed to identify independent predictors of iAEs. Sensitivity analyses were performed in uniform samples of operations.

Results

Of 9,292 patients, 218 iAEs were confirmed in 183 patients. Median patient age was 56 years old and 54% were female. Compared with patients without iAEs, iAE patients were older (median 61 vs 56 years; p < 0.001), more functionally dependent (9% vs 5%; p = 0.028), and had higher American Society of Anesthesiologists class (≥3 in 45% vs 35%; p = 0.004); their procedures were more complex (median relative value units 29 vs 23; p < 0.001), more likely open (48% vs 21%; p < 0.001), and more often required adhesiolysis (44% vs 18%; p < 0.001). In multivariable analyses, adhesiolysis (odds ratio = 2.34; 95% CI, 1.71–3.21; p < 0.001), higher operative complexity (third vs first relative value units quartile: odds ratio = 3.36; 95% CI, 1.66–6.78; p < 0.001; fourth vs first quartile: odds ratio = 5.97; 95% CI, 3.01–11.86; p < 0.001), and open surgical approach (odds ratio = 2.04; 95% CI, 1.39–3.01; p < 0.001) independently predicted iAEs. Sensitivity analyses confirmed adhesiolysis and higher operative complexity as independent iAE predictors.

Conclusions

Adhesiolysis and higher operative complexity predict an increased risk for iAE. Attempts to benchmark the quality of intraoperative care need to adequately risk adjust for these factors.

Risk Algorithm Using Serial Biomarker Measurements Doubles the Number of Screen-Detected Cancers Compared With a Single-Threshold Rule in the United Kingdom Collaborative Trial of Ovarian Cancer Screening + comments



 original article - open access


New Articles -- EvidenceUpdates - now includes comments


Abstract
PURPOSE: Cancer screening strategies have commonly adopted single-biomarker thresholds to identify abnormality. We investigated the impact of serial biomarker change interpreted through a risk algorithm on cancer detection rates.
PATIENTS AND METHODS: In the United Kingdom Collaborative Trial of Ovarian Cancer Screening, 46,237 women, age 50 years or older underwent incidence screening by using the multimodal strategy (MMS) in which annual serum cancer antigen 125 (CA-125) was interpreted with the risk of ovarian cancer algorithm (ROCA). Women were triaged by the ROCA: normal risk, returned to annual screening; intermediate risk, repeat CA-125; and elevated risk, repeat CA-125 and transvaginal ultrasound. Women with persistently increased risk were clinically evaluated. All participants were followed through national cancer and/or death registries. Performance characteristics of a single-threshold rule and the ROCA were compared by using receiver operating characteristic curves.
RESULTS: After 296,911 women-years of annual incidence screening, 640 women underwent surgery. Of those, 133 had primary invasive epithelial ovarian or tubal cancers (iEOCs). In all, 22 interval iEOCs occurred within 1 year of screening, of which one was detected by ROCA but was managed conservatively after clinical assessment. The sensitivity and specificity of MMS for detection of iEOCs were 85.8% (95% CI, 79.3% to 90.9%) and 99.8% (95% CI, 99.8% to 99.8%), respectively, with 4.8 surgeries per iEOC. ROCA alone detected 87.1% (135 of 155) of the iEOCs. Using fixed CA-125 cutoffs at the last annual screen of more than 35, more than 30, and more than 22 U/mL would have identified 41.3% (64 of 155), 48.4% (75 of 155), and 66.5% (103 of 155), respectively. The area under the curve for ROCA (0.915) was significantly (P = .0027) higher than that for a single-threshold rule (0.869).
CONCLUSION: Screening by using ROCA doubled the number of screen-detected iEOCs compared with a fixed cutoff. In the context of cancer screening, reliance on predefined single-threshold rules may result in biomarkers of value being discarded.

Comments from Clinical Raters
Gynecology
This is an important finding but it is secondary analysis/hypothesis generating and testing. It needs further investigating before it is used in clinical practice.
Oncology - Gynecology
This is a preliminary analysis. The core study remains ongoing, to answer the critical question of whether screening saves lives with an acceptable morbidity.

(+video) Advances in Ovarian Cancer Research: Exploiting Vulnerabilities



Meetings Notice AACR
  

Advances in Ovarian Cancer Research: Exploiting Vulnerabilities

October 17 - 20, 2015
Hyatt Regency Orlando
Orlando, Florida, USA
Abstract submission deadline: Monday, August 3
Advance registration deadline: Friday, September 4

Financial Distress and Its Associations With Physical and Emotional Symptoms and Quality of Life Among Advanced Cancer Patients



open access

Implications for Practice:
Financial distress is an important and common factor contributing to the suffering of advanced cancer patients and their caregivers. It should be suspected in patients with persistent, refractory symptom expression. Early identification, measurement, and documentation will allow clinical teams to develop interventions to improve financial distress and its impact on quality of life of advanced cancer patients

Thursday, July 23, 2015

Tumor Genetic Screening Programs: A Call to Action



open access

...... Perhaps the most important question raised by the study by Meric-Bernstam et al3 is whether enrollment onto a genotype-matched protocol is really the metric by which these important profiling efforts should be judged. We would instead argue that the standard should be whether these programs identify sufficient patients with specific alterations to allow researchers to design and conduct previously impractical, but potentially transformative, precision medicine studies. Meric-Bernstam et al found that mutations in only three actionable genes (PIK3CA, KRAS, and BRAF) were present in > 5% of the patients tested. Moreover, far lower rates of actionable alterations in many other genes, including AKT, EGFR, and ERBB2, were observed across a wide variety of tumor types. These findings clearly demonstrate the necessity of uncoupling highly multiplexed next-generation genomic screening from the therapeutic studies that seek to enroll these rare genetic subpopulations. To be certain, this type of outcome is much more difficult to measure but ultimately far more clinically meaningful. In sum, despite the challenges highlighted, we feel that the type of genomic screening initiative undertaken by Meric-Bernstam et al will be an increasingly critical part of a robust clinical trials program, and the authors should be applauded for their efforts.

REFERENCES

Wednesday, July 22, 2015

A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies



open access

 A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) 

..... To date, there is no standard tool for grading the magnitude of clinical benefit of cancer therapies [25, 26], which may range from trivial (median PFS advantage of only a few weeks) to substantial (improved long-term survival). Indeed, in the absence of a standardised approach for grading, the magnitude of clinical benefit, conclusions and recommendations derived from studies are often hotly disputed [25] and very modest incremental advances have often been presented, discussed and promoted as major advances or ‘breakthroughs’ [5, 2529]. Overestimating or overstating the benefits from new intervention can cause harm: it confounds public policy decision making [29], undermines the credibility of oncology research reporting [26, 29, 30], harms patients who choose to undertake treatments based on
exaggerated expectations that may subject them to either risk of adverse effects, inconvenience or substantial personal costs [26, 28] and, in the public domain, they fuel sometimes inappropriate hype or disproportionate expectations about novel treatments [31, 32] and the need to allocate public or personal funds to provide them....

 Table 7.
Field testing ESMO-MCBS v1.0: ovarian cancer

NeoGenomics Launches Germline Cancer Predisposition Testing -- FT. MYERS, Fla., July 20, 2015 /PRNewswire/ --



press release

The current NeoGenomics offering includes individual gene testing of BRCA1, BRCA2, MLH1, MSH2, EPCAM, MSH6, PMS2 genes as well as a comprehensive 73 gene panel that includes the following genes: AKT1, APC, ATM, ATR, BAP1, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, DKN2A, CEBPA, CHEK1, CHEK2, CTNNA1, EPCAM, ETV6, FAM175A, GALNT12, GATA2, GEN1, GREM1, HOXB13, KLLN, MEN1, MLH1, MRE11A, MSH2, MSH6, MUTYH, MYH1, MYH2, MYH3, MYH4, MYH6, MYH7, MYH8, MYH9, MYH10, MYH11, MYH13, MYH14, MYH15, NBN, NTRK1, PALB2, PIK3CA, PMS2, POLD1, POLE, PPM1D, PRSS1, PTEN, RAD50, RAD51, RAD51C, RAD51D, RET, RUNX1, SDHB, SDHC, SDHD, SMAD4, STK11, TERC, TERT, TP53, TP53BP1, VHL, WT1, XRCC2.

A Systematic Comparison of Traditional and Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Genes in More Than 1000 Patients



Abstract

 Gene panels for hereditary breast and ovarian cancer risk assessment are gaining acceptance, even though the clinical utility of these panels is not yet fully defined. Technical questions remain, however, about the performance and clinical interpretation of gene panels in comparison with traditional tests. We tested 1105 individuals using a 29-gene next-generation sequencing panel and observed 100% analytical concordance with traditional and reference data on >750 comparable variants. These 750 variants included technically challenging classes of sequence and copy number variation that together represent a significant fraction (13.4%) of the pathogenic variants observed. For BRCA1 and BRCA2, we also compared variant interpretations in traditional reports to those produced using only non-proprietary resources and following criteria based on recent (2015) guidelines. We observed 99.8% net report concordance, albeit with a slightly higher variant of uncertain significance rate. In 4.5% of BRCA-negative cases, we uncovered pathogenic variants in other genes, which appear clinically relevant. Previously unseen variants requiring interpretation accumulated rapidly, even after 1000 individuals had been tested. We conclude that next-generation sequencing panel testing can provide results highly comparable to traditional testing and can uncover potentially actionable findings that may be otherwise missed. Challenges remain for the broad adoption of panel tests, some of which will be addressed by the accumulation of large public databases of annotated clinical variants.

Vitamin D and pancreatic cancer: a pooled analysis from the Pancreatic Cancer Case–Control Consortium



abstract

 Conclusion Increased risk of pancreatic cancer was observed with higher levels of dietary vitamin D intake. Additional studies are required to determine whether or not our finding has a causal basis.

Common chemicals may act together to increase cancer risk, study finds



Cancer news


Journal Reference:
  1. Zhiwei Hu et al. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead. Carcinogenesis, 2015; 36 (Suppl 1): S254 DOI: 10.1093/carcin/bgv039

Prognostic impact of neuroendocrine differentiation in high-grade serous ovarian carcinoma



abstract

Neuroendocrine differentiation in high-grade serous ovarian carcinomas has only rarely been described. However, in our consultancy experience, we have been pointed at a case of neuroendocrine relapse in a patient with high-grade serous ovarian carcinoma where retrospectively, a minor neuroendocrine component in the primary tumor could be detected. Hypothesizing that immunohistochemical evidence of neuroendocrine differentiation might be more frequent in ovarian carcinoma than suspected by morphology, we immunophenotyped the tissue microarrays (TMAs) of a cohort of 178 high-grade serous carcinomas for chromogranin and synaptophysin expression. Synaptophysin expression was found in 12 (6.7 %) out of 172 patients, and chromogranin A expression was seen in 36 (20.7 %) out of 174 patients. Kaplan-Meier analysis revealed that carcinomas with synaptophysin expression of >20 % of positive cells (n = 4) had a significantly shorter survival time than those with 0-20 % of positive cells (p < 0.0001). Synaptophysin expression remained a significant prognostic factor in multivariate analysis (HR = 10.82, 95 % confidence interval 3.10-37.71, p < 0.0001), independently of age, FIGO stage, and residual tumor after surgery. A trend toward shorter survival was seen in patients with tumors that expressed chromogranin, irrespective of the amount of positive cells (p = 0.173). A neuroendocrine differentiation is important to keep in mind when a neuroendocrine tumor of unknown primary is detected in regional or temporal connection with an ovarian carcinoma. A minor neuroendocrine component in ovarian high-grade serous carcinomas might imply a dismal prognosis.

Carboplatin/taxane-induced gastrointestinal toxicity: a pharmacogenomics study on the SCOTROC1 trial



abstract

 Carboplatin/taxane combination is first-line therapy for ovarian cancer. However, patients can encounter treatment delays, impaired quality of life, even death because of chemotherapy-induced gastrointestinal (GI) toxicity. A candidate gene study was conducted to assess potential association of genetic variants with GI toxicity in 808 patients who received carboplatin/taxane in the Scottish Randomized Trial in Ovarian Cancer 1 (SCOTROC1). Patients were randomized into discovery and validation cohorts consisting of 404 patients each. Clinical covariates and genetic variants associated with grade III/IV GI toxicity in discovery cohort were evaluated in replication cohort. Chemotherapy-induced GI toxicity was significantly associated with seven single-nucleotide polymorphisms in the ATP7B, GSR, VEGFA and SCN10A genes. Patients with risk genotypes were at 1.53 to 18.01 higher odds to develop carboplatin/taxane-induced GI toxicity (P<0.01). Variants in the VEGF gene were marginally associated with survival time. Our data provide potential targets for modulation/inhibition of GI toxicity in ovarian cancer patients

High Prevalence of Hereditary Cancer Syndromes in Adolescents and Young Adults With Colorectal Cancer



abstract
 

RESULTS:

Of the 193 patients with evaluable data, 35% had an identifiable hereditary cancer syndrome, including 23 with Lynch syndrome, 22 with mutation-negative Lynch syndrome, 16 with familial adenomatous polyposis, two with constitutional mismatch repair deficiency, two with biallelic MUTYH mutations, and one with Li-Fraumeni syndrome. Patients without a hereditary syndrome more frequently presented with metastatic disease, whereas patients with a syndrome were more likely to present at earlier stages and to have a family history of cancer. Nevertheless, a substantial proportion of the hereditary syndromes (19%) were diagnosed in individuals with no family history of the disease.

Funding research to fill gaps in cancer knowledge - Cancer Prevention Research & Policy Blog



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Grant programmes | World Cancer Research Fund International



Grant programmes

About our Research Grant Programme

World Cancer Research Fund International’s Regular Grant Programme 2015/16 cycle is now open. The deadline for submitting applications is 9 October 2015.
Our Research Grant Programme funds research on the effects of diet, nutrition, body composition and physical activity on cancer prevention and survival - and is an important part our work to help achieve our vision of living in a world where no one develops a preventable cancer.
The research we fund as part of our Research Grant Programme, builds on and is informed by the scientific findings from our Continuous Update Project and Second Expert Report. In addition, the Research Grant Programme funds innovative research that focuses on our area of work: the link between diet, nutrition, body composition and physical activity on cancer prevention and survival.......

 Our Regular Grant Programme accepts applications from anywhere in the world, except the Americas (North America, Central America and the Caribbean, and South America). Applications from the Americas should be submitted to our network charity, the American Institute for Cancer Research, which offers a Research Grant Programme.

Tuesday, July 21, 2015

Administering Death, Terminating Suffering (Part 2)



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2016 Progress and Controversies in Gynecologic Oncology Conference



2016 Progress and Controversies in Gynecologic Oncology Conference

 We are pleased to invite you to the 2016 Progress and Controversies in Gynecologic Oncology Conference, to be held in Barcelona, Spain, on 22-23 January 2016.

Impact of Age and Primary Disease Site on Outcome in Women With Low-Grade Serous Carcinoma of the Ovary or Peritoneum



abstract

 Impact of Age and Primary Disease Site on Outcome in Women With Low-Grade Serous Carcinoma of the Ovary or Peritoneum: Results of a Large Single-Institution Registry of a Rare Tumor

Purpose Low-grade serous carcinoma of the ovary (LGSOC) or peritoneum (LGSPC) is a rare subtype of ovarian or peritoneal cancer characterized by young age at diagnosis and relative resistance to chemotherapy. The purpose of this study is to report our updated experience with women diagnosed with LGSOC or LGSPC to assess the validity of our original observations. 

Patients and Methods Eligibility criteria for patients from our database were: stage I to IV LGSOC or LGSPC, original diagnosis before January 2012, and adequate clinical information. All patients were included in progression-free survival, overall survival, and multivariable Cox regression analyses. A subset analysis was performed among patients with stage II to IV low-grade serous carcinoma treated with primary surgery followed by platinum-based chemotherapy. 

Results We identified 350 eligible patients. Median progression-free survival was 28.1 months; median overall survival was 101.7 months. In the multivariable analysis, compared with women age ≤ 35 years, those diagnosed at age > 35 years had a 43% reduction in likelihood of dying (hazard ratio, 0.53; 95% CI, 0.37 to 0.74; P < .001). Having disease present at completion of primary therapy was associated with a 1.78 increased hazard of dying compared with being clinically disease free (P < .001). Similar trends were noted in the smaller patient cohort. In this cohort, women with LGSPC had a 41% decreased chance of dying (hazard ratio, 0.59; 95% CI, 0.36 to 0.98; P = .04) compared with those with LGSOC. 

Conclusion Women age < 35 years with low-grade serous carcinoma and those with persistent disease at completion of primary therapy have the worst outcomes. Patients with LGSPC seem to have a better prognosis than those with LGSOC.

Intake of vitamins A, C, and E and folate and the risk of ovarian cancer in a pooled analysis of 10 cohort studies



abstract
 

Purpose

Vitamins A, C, and E and folate have anticarcinogenic properties and thus might protect against cancer. Few known modifiable risk factors for ovarian cancer exist. We examined the associations between dietary and total (food and supplemental) vitamin intake and the risk of invasive epithelial ovarian cancer.

Methods

The primary data from 10 prospective cohort studies in North America and Europe were analyzed. Vitamin intakes were estimated from validated food frequency questionnaires in each study. Study-specific relative risks (RRs) were estimated using the Cox proportional hazards model and then combined using a random-effects model.

Results

Among 501,857 women, 1,973 cases of ovarian cancer occurred over a median follow-up period of 7–16 years across studies. Dietary and total intakes of each vitamin were not significantly associated with ovarian cancer risk. The pooled multivariate RRs [95 % confidence intervals (CIs)] for incremental increases in total intake of each vitamin were 1.02 (0.97–1.07) for vitamin A (increment: 1,300 mcg/day), 1.01 (0.99–1.04) for vitamin C (400 mg/day), 1.02 (0.97–1.06) for vitamin E (130 mg/day), and 1.01 (0.96–1.07) for folate (250 mcg/day). Multivitamin use (vs. nonuse) was not associated with ovarian cancer risk (pooled multivariate RR = 1.00, 95 % CI 0.89–1.12). Associations did not vary substantially by study, or by subgroups of the population. Greater vitamin intakes were associated with modestly higher risks of endometrioid tumors (n = 156 cases), but not with other histological types.

Conclusion

These results suggest that consumption of vitamins A, C, and E and folate during adulthood does not play a major role in ovarian cancer risk.

Monday, July 20, 2015

Surgery Risks: Why Choosing the Right Surgeon Matters - Patient Safety



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....The issue of patient safety has been at the forefront of American health care since 1999, when the Institute of Medicine released “To Err Is Human,” a landmark report on the startling frequency of medical errors.
But since then, medical errors haven’t abated — recent studies estimate that at least 200,000 patients a year die in hospitals from preventable errors and complications related to their care, which would make patient harm the nation’s third-leading cause of death.
Some say one answer is allowing patients to see surgeons’ track records......

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10 Myths about Palliative Care - Infographic



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Minimizing chemotherapy-induced peripheral neuropathy: preclinical and clinical development of new perspectives



abstract
 
Introduction: Chemotherapy-induced peripheral neuropathies (CIPN) are a dose-limiting adverse effect of certain anticancer drugs (platinum salts, vinca alkaloids, taxanes, bortezomib, thalidomide, epothilones, eribulin). CIPN are mainly responsible for sensory disturbances and are associated with a decrease in quality of life. After the end of chemotherapy, CIPN can last for several months and even years. Unfortunately, recent meta-analyses of clinical trials have demonstrated that there is no univocal gold standard for the prevention and treatment of CIPN.

Areas covered: Using animal models of CIPN, several new strategies to prevent or treat CIPN are under development. These new strategies involve several pathways, including ion channels, neuroprotectants, glutamatergic neurotransmission, oxidative stress, cannabinoid system, inflammation, and mitochondrial functions.

Expert opinion: To date, based on meta-analyses of clinical trials, no drug can be proposed as a gold standard to prevent or treat CIPN. Consequently, there is a strong discrepancy between the optimistic results of animal studies and the poor outcomes of clinical trials. Pain assessment in preclinical and clinical studies is probably not the best outcome measurement tool and all these studies should include composite outcomes including the full complexity of CIPN symptoms, such as positive symptoms (pain, paresthesia, and dysesthesia) and negative ones (numbness).

The vitamin D question: what's the best advice?



Cancer World 

Sunday, July 19, 2015

Papillary thyroid carcinoma (PTC) in Lynch syndrome: 2 cases and discussion on Lynch syndrome behaviour/genetics



abstract

 We present here two cases of papillary thyroid carcinoma (PTC) in patients affected by Lynch syndrome (LS). The first case is a 47-year-old woman with typical hereditary non-polyposis colorectal cancer (HNPCC) syndrome, reported with endometrial and ovarian carcinoma at age 43, and colon cancer at age 45. The patient underwent total thyroidectomy and central node dissection in 2007, at 47 years old, with a histological diagnosis of PTC (T1aN1a). Molecular genetics showed a germ-line mutation of the MLH1 gene, 1858 G>T(E620X), with substitution of glycine with a stop codon at position 620. This mutation has pathogenetic significance and was considered responsible for the various tumours of the HNPCC spectrum. In particular, in the same kindred, spanning 5 generations, there were 5 members with colorectal cancer, 4 with endometrial cancer, 3 with gastric and 2 with breast cancer.

The second case is a 34-year-old man with typical HNPCC syndrome with colonic resection for colon cancer at age 21. The patient underwent total thyroidectomy with central and lateral node dissection in 2010, at age 34, with a histological diagnosis of PTC with nodal metastases (pT4N1b). Molecular genetic analysis showed a germ-line mutation of the MSH2 gene (thymine insertion at position 907). This mutation had pathogenetic significance and was considered responsible for HNPCC development. Two similar cases have been reported: a 39-year-old woman, and a 44-year-old woman, affected by HNPCC syndrome, with anaplastic thyroid carcinoma and undifferentiated thyroid carcinoma, respectively. We reviewed the Lynch syndrome literature on the history, genetics and expanding tumour spectrum of this condition.

Is Invasive Micropapillary Serous Carcinoma a Low-grade Carcinoma?



abstract

 "Invasive micropapillary serous carcinoma" has been proposed as a synonym for low-grade serous carcinoma by some expert pathologists. In contrast, Singer and colleagues reported that some serous carcinomas with conspicuous invasive micropapillary pattern (SC-IMPs) can show high-grade nuclear atypia. However, the molecular features of such tumors have not been well documented. The aim of this study was to demonstrate and emphasize the fact that high-grade serous carcinoma confirmed by immunohistochemistry and molecular analysis can show conspicuous invasive micropapillary pattern. We selected 24 "SC-IMPs" and investigated: (1) their morphologic features; (2) the immunostaining pattern of p53 protein; and (3) KRAS/BRAF/TP53 gene mutations. The 24 SC-IMPs were subdivided into low-grade and high-grade tumors based primarily on the nuclear atypia, with the mitotic rate used as a secondary feature: low grade (n=5) and high grade (n=19). Low-grade SC-IMPs were characterized by low-mitotic activity, absence of abnormal mitosis, presence of serous borderline tumor, occasional BRAF mutation, and infrequent TP53 mutation. High-grade SC-IMPs were characterized by high-mitotic activity, presence of abnormal mitosis, conventional high-grade serous carcinoma, frequent TP53 mutation, and lack of KRAS/BRAF mutation. We demonstrated that high-grade serous carcinoma confirmed by aberrant p53 immunostaining and molecular analysis can show conspicuous invasive micropapillary pattern, validating Singer and colleague's report. Serous carcinoma with conspicuous invasive micropapillary pattern should not be readily regarded as low-grade serous carcinoma. Nuclear grade is the most important diagnostic feature in the SC-IMPs.

Expression of P450 Aromatase in Granulosa Cell Tumors and Sertoli-Stromal Cell Tumors of the Ovary: Which Cells Are Responsible for Estrogenesis?



open access (pdf)

 Granulosa cell tumors are representative of estrogenic ovarian tumors, and some Sertoli-stromal cell tumors are also estrogenic. The exact cells that are responsible for estrogenesis, however, have yet to be identified. In the present study, 25 sex cord-stromal tumors (20 granulosa cell tumors, 4 Sertoli-Leydig cell tumors, and a Sertoli cell tumor) were immunohistochemically examined for expression of P450 aromatase, which is critical for estrogenesis. All of the tumors had been evaluated regarding their estrogenic function, including contemporaneous endometrial hyperplasia and/or elevation of serum estradiol. Eleven of 14 estrogenic granulosa cell tumors showed sparse or aggregated immunoreactivity for aromatase, whereas 5 of 6 nonestrogenic tumors did not. Aromatase was selectively expressed by plump granulosa cells with eosinophilic or vacuolated cytoplasm, resembling luteinized granulosa cells. Such a localization of aromatase is analogous to that in normal ovaries. Aromatase expression in primary tumors was recapitulated by recurrent tumors. In Sertoli-stromal cell tumors, either undifferentiated plump cells or well-differentiated Sertoli cells expressed aromatase. In conclusion, the expression of P450 aromatase corresponds to specific cell morphology in sex cord-stromal tumors, including recurrent tumors. Aromatase status in granulosa cell tumors provides helpful information on whether serum estradiol could be a marker for recurrence.

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0/

Intact PTEN Expression by Immunohistochemistry is Associated With Decreased Survival in Advanced Stage Ovarian/Primary Peritoneal High-grade Serous Carcinoma



abstract

 Ovarian high-grade serous carcinoma is an aggressive malignancy with poor prognosis. Optimal surgical debulking and tumor sensitivity to platinum-based chemotherapy are 2 well-established prognostics for this tumor type. Molecular markers that identify more clinically aggressive tumors would potentially allow for the development of individualized treatment options. PTEN is a key negative regulator of the PI3K signaling pathway. Loss of PTEN expression in endometrial carcinoma is associated with endometrioid histology; women with endometrioid tumors have a better prognosis than those with nonendometrioid tumors. The prognostic and predictive value for PTEN has not been effectively explored in ovarian/peritoneal high-grade serous carcinoma. PTEN immunohistochemistry was assessed in 126 women with Stage III, high-grade serous carcinoma of the ovary/peritoneum treated with surgery and then a platinum-based regimen. Compared with PTEN-negative or PTEN-reduced tumors, positive PTEN immunohistochemistry, detected in 58% of tumors, was associated with decreased pS6 and increased PTEN mRNA levels. Positive PTEN expression was independent of surgical debulking status or platinum sensitivity. PTEN-positive tumors were associated with significantly decreased recurrence-free survival. Importantly, the devised PTEN immunohistochemistry scoring system was reproducible among pathologists

Molecular Alterations of TP53 are a Defining Feature of Ovarian High-Grade Serous Carcinoma: A Rereview of Cases Lacking TP53 Mutations in The Cancer Genome Atlas Ovarian Study



abstract

 The Cancer Genome Atlas has reported that 96% of ovarian high-grade serous carcinomas (HGSCs) have TP53 somatic mutations suggesting that mutation of this gene is a defining feature of this neoplasm. In the current study, 5 gynecologic pathologists independently evaluated hematoxylin and eosin slides of 14 available cases from The Cancer Genome Atlas classified as HGSC that lacked a TP53 mutation. The histologic diagnoses rendered by these pathologists and the accompanying molecular genetic data are the subject of this report. Only 1 case (Case 5), which contained a homozygous deletion of TP53, had unanimous interobserver agreement for a diagnosis of pure HGSC. In 1 case (Case 3), all 5 observers (100%) rendered a diagnosis of HGSC; however, 3 observers (60%) noted that the histologic features were not classic for HGSC and suggested this case may have arisen from a low-grade serous carcinoma (arisen from an alternate pathway compared with the usual HGSC). In 2 cases (Cases 4 and 12), only 3 observers (60%) in each case, respectively, interpreted it as having a component of HGSC. In the remaining 10 (71%) of tumors (Cases 1, 2, 6-11, 13, and 14), the consensus diagnosis was not HGSC, with individual diagnoses including low-grade serous carcinoma, high-grade endometrioid carcinoma, HGSC, metastatic carcinoma, clear cell carcinoma, atypical proliferative (borderline) serous tumor, and adenocarcinoma, not otherwise specified. Therefore, 13 (93%) of the tumors (Cases 1-4 and 6-14) were either not a pure HGSC or represented a diagnosis other than HGSC, all with molecular results not characteristic of HGSC. Accordingly, our review of the TP53 wild-type HGSCs reported in The Cancer Genome Atlas suggests that 100% of de novo HGSCs contain TP53 somatic mutations or deletions, with the exception of the rare HGSCs that develop from a low-grade serous tumor precursor. We, therefore, propose that lack of molecular alterations of TP53 are essentially inconsistent with the diagnosis of ovarian HGSC and that tumors diagnosed as such should be rigorously reassessed to achieve correct classification.

Can Big Data cure cancer? - Fortune (+ google $$)



media (note reference to ovarian cancer)


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Pneumonitis an Adverse Effect of PD-Inhibitor Immunotherapy



Medscape

Ovarian Involvement in Endometrioid Adenocarcinoma of Uterus



abstract
 Published Online: July 14, 2015

OBJECTIVE:

Ovarian preservation is an option for some premenopausal patients with early stage endometrial cancer. Studies have shown that ovarian preservation in selected patients does not negatively impact survival outcomes. The objective of this study is to determine the frequency and characteristics of ovarian involvement when endometrial cancer is clinically confined to the uterus.

METHODS:

Patients with endometrioid adenocarcinoma of uterus treated at our institution between 2000 and 2013 were identified. Patients with ovarian metastasis or synchronous primary ovarian cancer were included. Patients were excluded if there was gross extrapelvic disease on examination or imaging.

RESULTS:

Seven hundred and fifty-nine patients were found to have endometrial cancer with the disease confined to the pelvis (stages I, II, and III). Fifteen patients (2%) had ovarian metastasis. Twenty-three patients (3%) had synchronous uterine and ovarian cancer. Most ovarian lesions (32 out of 38) were either enlarged or had abnormal appearing surface involvement. Six patients had microscopic ovarian involvement, accounting for 0.8% of the endometrial cancer patients with pelvis-confined disease. All of the patients were greater than 50 years of age. For those patients with microscopic ovarian metastasis, all had FIGO grade 3 disease, deep myometrial invasion, and extrauterine involvement of either cervix or lymph nodes.

CONCLUSIONS:

Microscopic ovarian involvement occurred in 0.8% of patients with endometrial cancer. For premenopausal patients with endometrial cancer, normal appearing ovaries may be considered for preservation in the absence of extrauterine spread, grade 3 disease and deep myometrial invasion.

recent articles (PubMed) Olaparib + ovarian cancer



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FDA (U.S.) Approval Summary: Olaparib Monotherapy in Patients with Deleterious Germline BRCA-Mutated Advanced Ovarian Cancer Treated with Three or More Lines of Chemotherapy



FDA abstract

 


On December 19, 2014, the FDA approved olaparib capsules (Lynparza™, AstraZeneca) for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. The BRACAnalysis CDx™ (Myriad Genetic Laboratories, Inc.) was approved concurrently. An international, multicenter, single-arm trial enrolled 137 patients with measurable, gBRCAm-associated ovarian cancer treated with three or more prior lines of chemotherapy. Patients received olaparib at a dose of 400 mg by mouth daily until disease progression or unacceptable toxicity. The overall response rate (ORR) was 34% with median response duration of 7.9 months in this cohort. The most common adverse reactions (≥20%) in patients treated with olaparib were anemia, nausea, fatigue (including asthenia), vomiting, diarrhea, dysgeusia, dyspepsia, headache, decreased appetite, nasopharyngitis/pharyngitis/URI, cough, arthralgia/musculoskeletal pain, myalgia, back pain, dermatitis/rash and abdominal pain/discomfort. Myelodysplatic syndrome and/or acute myeloid leukemia occurred in 2% of the patients enrolled on this trial.

Drugs with potential chemopreventive properties in relation to epithelial ovarian cancer - a nationwide case-control study. - PubMed - NCBI



thesis

Ovarian cancer has a poor prognosis because the disease in the majority of patients is diagnosed at an advanced stage as a result of nonspecific symptoms and lack of efficient screening methods. Because of the poor prognosis of ovarian cancer and the challenge of early detection of the disease, identification of protective factors is important. It has been suggested that some commonly used drugs may have a protective effect against cancer, including ovarian cancer; however, the literature on chemopreventive measures for ovarian cancer is sparse and the results are inconclusive. Most previous studies have substantial methodological constraints, including limited study size and self-reporting of drug use, which introduces potential recall bias and misclassification. This PhD thesis includes a nationwide case-control study to evaluate associations between use of drugs with potential chemopreventive properties and risk of epithelial ovarian cancer. The study is nested in the entire Danish female population using data from the following nationwide registries: the Danish Cancer Registry, the Danish Civil Registration System, the Danish Prescription Registry, the Danish National Patient Register, and registries in Statistics Denmark on fertility, education, and income. Information from the included registries is linked by use of the unique personal identification number assigned to all Danish citizens. The cases were all women in Denmark with epithelial ovarian cancer diagnosed during 2000-2009 (Paper 1) and 2000-2011 (Papers 2 and 3), identified in the Cancer Registry. Age-matched female population controls were randomly selected from the Civil Registration System by risk-set sampling. We required that cases and controls have no history of cancer (except non-melanoma skin cancer) and that controls not previously have undergone bilateral oophorectomy or salpingo-oophorectomy. The total study population comprised 3741 epithelial ovarian cancer cases and 50,576 controls in Paper 1, and 4103 epithelial ovarian cancer cases and 58,706 controls in Papers 2 and 3. We used the Danish Prescription Registry to assess use (≥2 prescriptions on separate dates) of paracetamol, non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin, and statins. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for epithelial ovarian cancer associated with use of the study drugs, with adjustment for potential confounding factors selected a priori. We performed detailed analyses according to duration, intensity, and continuity of study drug use, and the analyses were stratified according to specific histologic types of epithelial ovarian cancer. In all studies, non-use (< 2 prescriptions) of the individual study drugs was defined as the reference group. A striking result of the PhD thesis was a strong inverse association between prescription use of paracetamol and risk of epithelial ovarian cancer. The risk estimates decreased with increasing duration and intensity of paracetamol use, reaching a more than 50% reduction for the longest duration (>10 years) and the highest doses (OR: 0.45; 95% CI: 0.24-0.86). In contrast, we did not observe an inverse association between use of non-aspirin NSAIDs and risk of epithelial ovarian cancer. Moreover, this thesis provides further evidence that use of low-dose aspirin is associated with a reduced risk of epithelial ovarian cancer. In particular, long-term (≥5 years) continuous use of low-dose aspirin, defined as overlapping prescription coverage periods, was associated with a large reduction in risk (OR: 0.56; 95% CI: 0.32-0.97). Finally, we found no apparent association between statin use and epithelial ovarian cancer risk, although the analysis by histologic type suggested an inverse association with the risk of mucinous tumors. The results of this PhD thesis add important knowledge to the area of chemoprevention in relation to epithelial ovarian cancer. As for any observational study, we cannot exclude potential con-founding and exposure misclassification; however, methodological limitations appear unlikely to fully explain the observed reductions in epithelial ovarian cancer risk associated with paracetamol and low-dose aspirin use. Additional research, ideally from clinical trials, is needed before our observations may lead to recommendations for chemopreventive measures against ovarian cancer. In case consensus points to a true protective effect of paracetamol or low-dose aspirin, comprehensive risk-benefit evaluations will also have to be performed. We hope that our results will encourage researchers to look more deeply into the potential chemo-preventive effects of the study drugs against epithelial ovarian cancer risk.