Mismatch Repair Protein Expression in Clear Cell Carcinoma of the Ovary

Mismatch Repair Protein Expression in Clear Cell Carcinoma of the Ovary: Incidence and Morphologic Associations in 109 Cases

Abstract

Several morphologic features have been reported to be predictive of abnormal expression of mismatch repair (MMR) proteins in endometrial and colon carcinomas. Although it is known that abnormal MMR expression is increased in frequency in ovarian endometrioid and clear cell carcinomas, no such histologic correlation has been identified. We reviewed 109 unselected ovarian clear cell carcinomas for specific tumor characteristics (architecture, nuclear atypia, signet ring cells, stromal hyalinization, background precursor) and inflammatory response (peritumoral lymphocytes found along the leading edge of the tumor, intratumoral stromal inflammation found within the tumor, percentage of plasma cells in the intratumoral stromal inflammation, tumor-infiltrating lymphocytes) and performed immunohistochemistry for all 4 MMR proteins. Abnormal MMR expression was identified in 6% of tumors and included MSH2/MSH6 (3), MLH1/PMS2 (1), MSH6 (1), and PMS2 (1). These patients had a mean age of 40 (range, 31 to 48) years, which contrasted with a mean of 53.2 (range, 28 to 82) years for the overall cohort. One had a concurrent diagnosis of endometrial carcinoma, whereas another had a family history of endometrial carcinoma. None had a personal/family history of colonic carcinoma. Tumors with diffuse intratumoral stromal inflammation and peritumoral lymphocytes were more frequently associated with MMR loss on univariate analysis (P<0.001 and 0.047, respectively) with diffuse intratumoral stromal inflammation remaining a significant independent predictor on multivariate analysis. None of the other morphologic features evaluated reached statistical significance. Although previous series have been unable to identify a relationship between histology and MMR expression, this study identified a correlation with diffuse intratumoral stromal inflammation and peritumoral lymphocytes, 2 features that potentially could be selected for MMR analysis if corroborated by other studies.

Long-term Benefit of Tumor Volume-Directed Involved Field Radiation Therapy in the Management of Recurrent Ovarian Cancer

abstract

define: IFRT +  delivering radiation to only those areas of the body involved

OBJECTIVES:

This study aimed to report on long-term effectiveness of involved field radiation therapy (IFRT) in the salvage of localized recurrent ovarian cancer (ROC).

METHODS:

A retrospective analysis of 27 patients with a diagnosis of epithelial ovarian cancer who received tumor volume-directed IFRT for localized extraperitoneal recurrences (either as consolidation after cytoreductive surgery (CRS) or as attempted salvage if unresectable) forms the basis of this report. All patients were heavily pretreated with multiple chemotherapy regimens. Involved field radiation therapy was primarily with external beam (median dose, 50.4 Gy). Local recurrence-free survival (LRFS) was defined as freedom from in-field recurrences and was considered as a measure of effectiveness of radiotherapy. Statistical analyses evaluated association between disease-free survival, overall survival, LRFS, and various prognostic factors. Comparison was also made with a similar but unmatched cohort with localized recurrences salvaged by additional chemotherapy instead of local therapies (NIFRT group).

Preoperative experience for public hospital patients with gynecologic cancer

abstract
 Preoperative experience for public hospital patients with gynecologic cancer: Do structural barriers widen the gap?

BACKGROUND

Widespread disparities in care have been documented in women with gynecologic cancer in the United States. This study was designed to determine whether structural barriers to optimal care were present during the preoperative period for patients with gynecologic cancer.

METHODS

A retrospective review was conducted for patients undergoing surgery for a gynecologic malignancy at a public hospital or a private hospital staffed by the same team of gynecologic oncologists between July 1, 2013 and July 1, 2014.

RESULTS

Two hundred fifty-seven cases were included for analysis (public hospital, 69; private hospital, 188). Patients treated at the private hospital were older (58 vs 52 years; P = .004) and had similar medical comorbidities (median Charlson comorbidity index at both hospitals, 6) but required fewer hospital visits in preparation for surgery (2 vs 4; P < .001). Public hospital patients had a longer wait time from the diagnosis of disease to surgery (63 vs 34 days; P < .001). According to a multiple linear regression model, the public hospital setting was associated with a longer interval from diagnosis to surgery with adjustments for the insurance status, age at diagnosis, cancer stage, and number of preoperative hospital visits (P < .001).

CONCLUSIONS

Patients at the public hospital were subject to a greater number of preoperative visits and had to wait longer for surgery than patients at the private hospital. Attempts to reduce health care disparities should focus on improving efficiency in health care delivery systems once contact has been established.

Meet the experts at our new event: 'Science, theory and advances in ovarian cancer' conference June 2016 (UK)

Target Ovarian Cancer


Target Ovarian Cancer is very proud to present its second flagship 'Ask the Experts' event: 'Science, theory and advances in ovarian cancer'. In June 2016, in Birmingham, we will bring together eminent experts for presentations and Q&As on the cutting edge of ovarian cancer news and research. This free information event is open to all women with ovarian cancer, their families and their friends.
Leading figures including oncologists, clinical nurse specialists, GPs, researchers and more will give presentations on a range of topics including:

• screening, risk and earlier diagnosis
• treatment and research
• living well with ovarian cancer

Attendees will then have the opportunity to put their questions to leading local clinicians and our panel of experts.

PR release needs more evidence for its exceptional ovarian cancer claims

HealthNewsReview.org

  Our Review Summary

This news release summarizes a review article published in Nature Reviews Clinical Oncology which assesses the available evidence and makes recommendations concerning the treatment of advanced ovarian cancer. The author of the review argues that adopting a more aggressive standard of treatment for this cancer type that involves locally directed adjuvant chemotherapy could increase cure rates from 20% to 50%. The news release uses some of the language in the review but, unsurprisingly, it appears more optimistic than the perspective piece. The release doesn’t address costs or harms related to such a course of  treatment, nor does it give readers any information about how the original article reached the conclusion that survival rates could be increased up to 50 percent. Exceptional claims require exceptional evidence, and that’s missing here.....

Understanding genistein in cancer: The “good” and the “bad” effects: A review

abstract
  

Highlights

•

Genistein biological activities strongly differ in relation to doses applied.

•

Genistein targets primarily estrogen receptors and tyrosine kinases.

•

Potential therapeutic effects of genistein may depend upon the pleiotropic nature of the molecule.

---

Abstract

Nowadays, diet and specific dietary supplements are seen as potential adjuvants to prevent different chronic diseases, including cancer, or to ameliorate pharmacological therapies. Soybean is one of the most important food components in Asian diet. A plethora of evidence supports the in vitro and in vivo anticancer effects of genistein, a soybean isoflavone. Major tumors affected by genistein here reviewed are breast, prostate, colon, liver, ovarian, bladder, gastric, brain cancers, neuroblastoma and chronic lymphocytic leukemia. However, it is not always clear if and when genistein is beneficial against tumors (the “good” effects), or the opposite, when the same molecule exerts adverse effects (the “bad” effects), favouring cancer cell proliferation. This review will critically evaluate this concept in the light of the different molecular mechanisms of genistein which occur when the molecule is administered at low doses (chemopreventive effects), or at high doses (pharmacological effects).

Keywords

• Soybean;
• Genistein;
• ERα/ERβ;
• Tyrosine kinases;
• miRNA

Genetic discrimination law urgently needed, medical experts say (Canada)

 CBC News
   
(Toronto) Sick Kids Hospital genetics head calls absence of confidentiality legislation 'paralyzing'
 
"There's no protection against genetic discrimination at all," Dr. Ronald Cohn, chief of genetics at the Hospital for Sick Children in Toronto, told CBC News.
Bill S-201 — also known as the Genetic Non-Discrimination Act — passed second reading in the Senate earlier this week. The legislation would specifically prohibit insurance companies, employers and other third parties from accessing people's genetic test results.....

External Links

• Bill S-201 Genetic Non-Discrimination Act
• Canadian Life and Health Insurance Association: Genetic testing
• Canadian Coalition for Genetic Fairness

Cancer Conversations Podcast – Episode #2: The Truth About BRCA Testing and Genetic Risk

Podcast – Episode #2 (24 min)
 
Although only a small percentage of breast cancers are considered hereditary, genetic testing and cancer risk — specifically the BRCA1/2 genes — have made many headlines in recent years. But what exactly does it mean to have a BRCA mutation, and what do women need to know?
In this Cancer Conversations podcast episode, Huma Rana, MD, clinical director of Dana-Farber’s Center for Cancer Genetics and Prevention, gives an overview of the link between genetics and women’s cancers, and why certain women have a higher risk for developing disease.
Listen to the podcast episode below or click “download” to listen later. Subscribe options are also available via iTunes, Google Play and RSS.
The Cancer Conversations series features Q&A-style conversations with Dana-Farber physicians, clinicians, and researchers. Topics include breast cancer research, precision cancer medicine, integrative therapies, cancer genetics, and more. Visit the Cancer Conversations page for more episodes.
Learn more about Dana-Farber’s Cancer Podcast Series.

Podcast: Play in new window | Download

Prognostic factors in Polish patients with BRCA1-dependent ovarian cancer

open access

Background

Treatment outcomes appear to be better for ovarian cancer (OC) patients carrying the BRCA1/2 germline mutation than for patients with sporadic OC. However, most published data are for North American, British and Jewish populations. There have been very few studies on treatment outcomes in Central and Eastern European patients with OC. The aim of this study was to analyse prognostic factors in Polish patients with BRCA1-dependent OC (BRCA1-OC). 

 

Conclusion

Prognostic factors for favourable treatment outcomes in Polish patients with BRCA1-OC do not appear to differ from those in patients with sporadic OC. The incidence of the endometrial subtype of OC was relatively high (34.9 %) among women in the study. This was unexpected and has not been reported previously. This subtype of OC was an independent prognostic factor for favourable treatment outcomes.

Trends in gynecologic cancer among elderly women in Denmark, 1980–2012

abstract

 For ovarian and Fallopian tube cancers the incidence was almost constant, whereas the average annual number of deaths decreased over time from 466 in 1980 to 396 in 2012. The mortality rates were clearly separated by age groups with mortality rates 3–4 times higher among the elderly. The mortality rate decreased among women less than 70 years during the entire period.

Are Early Relapses in Advanced-Stage Ovarian Cancer Doomed to a Poor Prognosis?

PLOS ONE (open access)
 

Objective

Early recurrence (ER) after completion of therapeutic regimen in advanced-stage ovarian cancer is a challenging clinical situation. Patients are perceived as invariably having a poor prognosis. We investigated the possibility of defining different prognostic subgroups and the parameters implicated in prognosis of ER patients.

Conclusion

ER (early recurrence) in advanced-stage ovarian cancer does not inevitably portend a short-term poor prognosis. RD (residual disease) status after initial cytoreduction strongly modulates OS, that gives additional support to the concept of maximum surgical effort even in patients who will experience early recurrence. The heterogeneity in outcomes within the ER group suggests a role for tumor biology in addition to classical clinical parameters.

SGO Annual Meeting (March 2016) on Women's Cancer San Diego (abstracts)

 SGO

Abstract titles now available

Session times, abstract titles, authors and institutions are now available online for the SGO Annual Meeting in San Diego. Full abstracts will become available on the day of the session on which they will be presented.

 

• Friday, March 18, 2016
• Saturday, March 19, 2016
• Sunday, March 20, 2016
• Monday, March 21, 2016
• Tuesday, March 22, 2016 

Index of Speakers

Feb 2016 Index: International Journal of Gynecological Cancer

Current Issue

Routine Clinical Practice for Patients With Recurrent Ovarian Carcinoma: Results From the TROCADERO Study

open access

 This study characterized the clinical features and prognosis of patients with recurrent ovarian carcinoma with respect to platinum sensitivity. The primary objective was to evaluate PFI among PPS patients who received platinum-containing treatment at first recurrence relative to those patients who did not. Data regarding clinical characteristics, incidence and duration of clinical events, and treatment regimen are reported.

Clinical and Pathological Characteristics of Incidental Diagnostic Early Occult Malignancy After Risk-Reducing Salpingo-Oophorectomy in BRCA Mutation Carriers

open access

 CONCLUSIONS

Our study demonstrated an incidence of early occult malignancy of 5.4% among BRCA mutation carriers who underwent RRBSO. This falls within the middle ranges of reported data (1.3%–10.4%). Origin sites for the discovered malignancies were in the ovaries and in the fallopian tubes. These data support the notion that such malignancies may originate from the fallopian tube, although the fallopian tubes are not a unique site of origin. Further study may explain the different origins of carcinogenesis. Continued screening of women at high risk and recommendation of early and meticulous RRBSO are crucial to limit the risk of ovarian and tubal carcinogenesis.

 

Abstract

Objective: Carriers of familial BRCA mutations are at high risk of early development of ovarian tubal or peritoneal cancers. The definite preventative treatment for these cases is early, risk-reducing, bilateral salpingo-oophorectomy (BSO). The aims of the study were to describe the incidence and source of early occult malignancy after risk-reducing salpingo-oophorectomy in carriers of Ashkenazi Jewish BRCA mutations and to characterize the clinical and pathological features of this unique population.

Methods: Data were collected retrospectively regarding women who underwent BSO in our gynecologic oncology unit from January 2002 through July 2012, after a positive test for a BRCA1 or BRCA2 mutation.

Results: The following 92 cases of BRCA mutations were included: 53 BRCA1, 37 BRCA2, and 2 with both mutations. After risk-reducing salpingo-oophorectomy, 5 (5.4%) of the patients were found to have early occult adnexal malignancy upon pathology study. All 5 had the BRCA1 185 del-AG mutation. Three of the 5 malignancies originated from the ovaries and 2 in the fallopian tubes with no involvement of the ovaries.

Conclusions: A 5.4% incidence of early occult malignancy in adnexal pathology of BSO was found in carriers of Ashkenazi Jewish BRCA mutations. Two cases with malignant origins within the fallopian tube, while sparing the ovaries in their entirety, support the fallopian tubes as the originating organ for some ovarian or peritoneal malignancies in BRCA mutation carriers.

Loss of Mismatch Repair Protein Expression in Unselected Endometrial Adenocarcinoma Precursor Lesions

open access

Letter to the Editor on “Should All Cases of High-Grade Serous Ovarian, Tubal, and Primary Peritoneal Carcinomas Be Reclassified as Tubo-Ovarian Serous Carcinoma?”

open access

.....

In our opinion, the fact that one tumor type (HGSC) accounts for more than two thirds of the cases does not justify classifying ovarian carcinomas into only 2 types, lumping together the other four (low-grade endometrioid, clear cell, mucinous, and low-grade serous carcinomas) as “type 1 carcinomas”. In fact, the latter tumors are clinically, morphologically, and molecularly distinct diseases that individually bear resemblance neither to HGSCs nor to each other. Thus, classifying ovarian carcinomas into just 2 types (“types 1 and 2”) is artificial and limits progress in understanding the biology or improving the management of the less common types of ovarian carcinomas. When preparing this, we were reminded of the words of the eminent Scandinavian investigators of earlier times Drs. Lars Santesson and Hans Ludwig Kottmeier who began an essay on the classification of ovarian tumors as follows: “Ovarian cancer is not an entity but a group of diseases. Studies of the results of treatment must be based on homogeneous groups of tumours and not on mixtures of histologically and biologically different tumour types”.³

Just a few of the many differences between the entities in the grouping “type 1” carcinoma are the following: endometrioid and clear cell tumors have a very significant association with endometriosis, not seen, except rarely, with mucinous carcinomas and LGSCs. Additionally, endometrioid and clear cell carcinomas often have an origin in adenofibromas, also rarely seen with the other 2 tumor types. Mucinous tumors in an uncertain but definitely notable percentage of cases are likely of teratomatous origin, which is completely lacking for the other 3 tumor types....

 We think that terms such as tubo-ovarian, müllerian, or pelvic serous carcinoma should not be recommended because they create confusion for patients, physicians, and medical investigators. In view of the rarity of HGSCs associated with tubal tumor masses, it is unlikely that all HGSCs originate in the fallopian tube. In contrast, ovarian involvement is the rule in almost all cases. The term HGSC of ovary should be kept until the different origins of ovarian tumors are better understood.¹⁵

 REFERENCES

1. Moss EL, Evans T, Pearmain P, et al. Should all cases of high-grade serous ovarian, tubal, and primary peritoneal carcinomas be reclassified as tubo-ovarian serous carcinoma? Int J Gynecol Cancer. 2015; 25: 1201–1207.

Cited Here...

Necessary Versus Sufficient: An Increasingly Relevant Distinction in Oncology (ref to ovarian cancer)

clinical oncology article (Markman)

 In summary, it is essential that any organization, as well as individual clinicians attempting to interpret the results of clinical studies, appreciate the critical distinction between what is appropriately considered to be necessary evidence versus the ultimate mandate for sufficient evidence in the future development of specific medical recommendations, evidence-based guidelines, or public health policy.

 References

1. Le Tourneau C, Delord JP, Goncalves A, et al. Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicenter, open-label, proof-of-concept, randomized, controlled phase 2 trial. Lancet Oncol. 2015;16(13):1324-1334, PMID: 26342236.
2. Jacobs IJ, Menon U, Ryan A, et al. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): A randomized controlled trial. Lancet. [Epub ahead of print]. DOI: http://dx.doi.org/​10.1016/​S0140-6736(15)01224-6.
3. Buys SS, Partridge E, Black A, et al. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA. 2011;305(22): 2295-2303, PMID: 21642681.
4. Grady D. Early detection of ovarian cancer may become possible. The New York Times. December 18, 2015. http://goo.gl/​WN7CPT. Accessed December 22, 2015.

video: The changing Nature of Phase 1 Clinical Trials (Dr. Lillian Siu)

Chromeless Video Player (39 min)

 The Changing Nature of Phase I Trials

Lillian Siu, MD, FRCRC

 

Lillian L. Siu, MD, Princess Margaret Cancer Center, University of Toronto, discussed the changing nature of phase I clinical trials, and how these changes are influencing the development and approval trajectories of novel cancer therapeutics.

Common Cancer Myths and Misconceptions - National Cancer Institute

National Cancer Institute

Identification of a Japanese Lynch syndrome patient with large deletion in the 3′ region of the EPCAM gene

abstract

Germline deletion of the 3′ portion of the Epithelial Cell Adhesion Molecule (EPCAM) gene located 5′ upstream of MutS Homolog 2 (MSH2) is a novel mechanism for its inactivation in Lynch syndrome. However, its contribution in Japanese Lynch syndrome patients is poorly understood. Moreover, somatic events inactivating the remaining allele of MSH2 in cancer tissue have not been elucidated in Lynch syndrome patients with such EPCAM deletions. We identified a Japanese Lynch syndrome patient with colon cancer who evidenced germline deletion of a 4130 bp fragment of EPCAM encompassing exons 8 and 9 (c.859-672_*2170del). In normal colonic mucosa, two known fusion-transcripts of EPCAM/MSH2 generated from the rearranged gene were observed and heterozygous methylation of the MSH2 gene promoter was detected. In cancer tissue, dense methylation of MSH2 was observed and MLPA analysis demonstrated somatic deletion of the remaining EPCAM allele including exon 9, indicating that somatic deletion of EPCAM is responsible for complete inactivation of MSH2. 

Preventing Damage Limitation: Targeting DNA-PKcs and DNA Double-Strand Break Repair Pathways for Ovarian Cancer Therapy

open access

...The promise of PARP inhibition strategies and DNA-PKcs as a therapeutic target highlights the importance of understanding the clinical significance of the functioning and defective DNA repair mechanisms in cancer. There remains the need to identify reliable biomarkers of tumor cell response and resistance to therapies targeting DNA repair proteins and indeed to identify and validate new therapeutic targets from this critical but insufficiently mined resource. The identification of patient subgroups who will benefit most from such strategies is also required – DDR proteins such as DNA-PKcs have been suggested to have a tumor-suppressive role in the early stages of carcinogenesis where ineffective DDR may contribute to the generation of genomic instability that drives tumor progression (99). As such, the development of DNA-PKcs inhibitions, and indeed other DDR targeted therapies, should be mindful of DNA damage thresholds that can be either oncogenic or tumor-suppressive, depending on the tumor stage. Together, such knowledge and understanding will translate into the development of new directed strategies that will help overcome clinical platinum resistance in ovarian cancer, and by that reduce patient mortality.

Ovarian Cancer Molecular Stratification and Tumor Heterogeneity: A Necessity and a Challenge

open access

The Future

Clearly, future optimal therapy for high-grade serous ovarian cancer will depend on optimal molecular stratification and this is just as true for bevacizumab and olaparib as it will be for future agents. While this will help rise to the challenge of optimizing therapy for inter-patient molecular heterogeneity, monotherapy may never overcome intra-patient heterogeneity. If we want to improve the durability of responses, that pool of resistant clones may need to be narrowed by using combination therapies. Indeed, recent clinical data for the addition of the VEGFR inhibitor, cedirinib, to olaparib have shown a significant increase in response rate and a near-doubling of progression free survival (47). The majority of this benefit was in the BRCA1/BRCA2 wild-type (or unknown) group, perhaps demonstrating that combinations can overcome monotherapy dependencies but also highlighting that there is still a lot to learn about biomarkers for anti-angiogenic and PARP inhibitor agents in ovarian cancer.

Disseminated Medulloblastoma in a Child with Germline BRCA2 6174delT Mutation and without Fanconi Anemia

open access

 Here, we report for the first time on a child carrying a familial heterozygous BRCA2 6174delT germline mutation, who presented with metastatic medulloblastoma. We also provide characterization of his tumor and the unique pair of medulloblastoma cell lines generated from it at diagnosis and at the time of systemic metastatic recurrence.

Cancer touches each of us. Share your story with the Vice President. | The White House

The White House

Clinical Trials Search Results - NCI ovarian epithelial cancer (7 results)

NCI

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Cancer Type/Condition:  Ovarian epithelial cancer
Added in last 30 days?:  Yes

Family History of Cancer in Relation to Breast Cancer Subtypes in African American Women

abstract

Background: The evidence on the relation of family history of cancers other than breast cancer to breast cancer risk is conflicting, and most studies have not assessed specific breast cancer subtypes. 

Methods: We assessed the relation of first-degree family history of breast, prostate, lung, colorectal, ovarian, and cervical cancer and lymphoma or leukemia, to the risk of estrogen receptor–positive (ER⁺), ER⁻, and triple-negative breast cancer in data from the African American Breast Cancer Epidemiology and Risk Consortium... 

Results: There were 3,023 ER⁺ and 1,497 ER⁻ breast cancer cases (including 696 triple-negative cases) and 17,420 controls. First-degree family history of breast cancer was associated with increased risk of each subtype: OR = 1.76 (95% CI, 1.57–1.97) for ER⁺, 1.67 (1.42–1.95) for ER⁻, and 1.72 (1.38–2.13) for triple-negative breast cancer. Family history of cervical cancer was associated with increased risk of ER⁻ (OR = 2.39; 95% CI, 1.36–4.20), but not ER⁺ cancer. Family history of both breast and prostate cancer was associated with increased risk of ER⁺ (3.40; 2.42–4.79) and ER⁻ (2.09; 1.21–3.63) cancer, but family history of both breast and lung cancer was associated only with ER⁻ cancer (2.11; 1.29–3.46). 

Conclusions: A family history of cancers other than breast may influence the risk of breast cancer, and associations may differ by subtype. 

Impact: Greater surveillance and counseling for additional screening may be warranted for women with a family history of cancer

Early-Stage Clinical Trials Underestimate Small Molecule, Targeted Anticancer Drug Toxicity

OncoTherapy Network

Dose-determining phase I clinical trials may not correctly determine the appropriate doses of small molecule oncology drugs to administer in larger, later stage trials according to a new study published in Clinical Cancer Research.

Phase I, dose-elevating clinical trials in a small number of patients are the standard way to determine the appropriate doses to test in later stage clinical trials. These small trials analyze pharmacokinetics, pharmacodynamics, and toxicity to determine the drug doses and schedules that are most likely to balance safety and efficacy.
The current study, conducted by researchers at The Institute of Cancer Research  and the Royal Marsden Hospital NHS Foundation Trust in the United Kingdom, suggests that phase 1 dose-ranging studies do not correctly reveal the severity of side effects of these cancer agents. The result is high incidence of varying drug toxicity experienced by patients taking part in phase III oncology clinical trials testing targeted small molecule agents.......

Drug Index (alphabetical order)

 

Drug Index

Ultrasounds Improve Diagnosis for Ovarian CancerTrending

Blogger's Note: same subject/different source

article

.... "A simple classification based on these risk estimates may form the basis of a clinical management approach. This will hopefully facilitate choosing optimal treatment for all patients presenting with adnexal masses."

In an editorial review of the study, Dr. Beryl Benacerraf, President of the American Institute of Ultrasound in Medicine (AIUM) and Clinical Professor of Radiology and OB GYN at Brigham and Women's Hospital, commented on the innovative simplicity of this new diagnostic method.

"The investigators have finally been able to level and elevate the playing field so that everybody can practice with expert results in this regard," Benacerraf said. "Not only have the five simple rules demonstrated that you don't have to be an expert to evaluate ovarian masses accurately, but that one can do so simply, reproducibly and reliably."....

Editorial: Allowing assisted suicide isn’t complicated. Just do it, Ottawa

The Globe and Mail

Role of Increased n-acetylaspartate Levels in Cancer

abstract
 

Background: The clinical and biological effects of metabolic alterations in cancer are not fully understood.

Methods: In high-grade serous ovarian cancer (HGSOC) samples (n = 101), over 170 metabolites were profiled and compared with normal ovarian tissues (n = 15). To determine NAT8L gene expression across different cancer types, we analyzed the RNA expression of cancer types using RNASeqV2 data available from the open access The Cancer Genome Atlas (TCGA) website (http://www.cbioportal.org/public-portal/). Using NAT8L siRNA, molecular techniques and histological analysis, we determined cancer cell viability, proliferation, apoptosis, and tumor growth in in vitro and in vivo (n = 6–10 mice/group) settings. Data were analyzed with the Student’s t test and Kaplan-Meier analysis. Statistical tests were two-sided.

Results: Patients with high levels of tumoral NAA and its biosynthetic enzyme, aspartate N-acetyltransferase (NAT8L), had worse overall survival than patients with low levels of NAA and NAT8L......

Conclusion: These findings indicate that the NAA pathway has a prominent role in promoting tumor growth and represents a valuable target for anticancer therapy.

Altered energy metabolism is a hallmark of cancer (1). Proliferating cancer cells have much greater metabolic requirements than nonproliferating differentiated cells (2,3). Moreover, altered cancer metabolism elevates unique metabolic intermediates, which can promote cancer survival and progression (4,5). Furthermore, emerging evidence suggests that proliferating cancer cells exploit alternative metabolic pathways to meet their high demand for energy and to accumulate biomass (6–8).

2016 Progress and Controversies in Gynecologic Oncology Conference - download slides

Activity Overview

prIME Oncology invites you to view downloadable slides from the 2016 Progress and Controversies in Gynecologic Oncology Conference held in Barcelona, Spain.

Bleomycin-Induced Flagellate Erythema in a Patient Diagnosed with Ovarian Yolk Sac Tumor

open access

 Flagellate linear hyperpigmentation can rarely be caused by the chemotherapy agent, bleomycin. Herein, we describe the case of a 20-year-old woman treated with bleomycin for an ovarian yolk sac tumor and review the prominent features of this form of dermatitis.

 2. Material

We report the case of a 20-year-old woman with no significant past medical or surgical history. An ultrasound examination demonstrated a suspicious ovarian cyst in pregnancy and the patient underwent fertility-preserving ovarian cancer resection with left oophorectomy. Routine pathological examination revealed replacement of the cyst by yolk sac tumor with a minor component of mature cystic teratoma.....

Borderline ovarian tumours: a continuing conundrum?

Commentary

 Whereas benign and malignant primary tumours of the ovary are well understood clinically, the concept of borderline ones are less so. Of the epithelial tumours of the ovary, the concept is best described in serous tumours, and less so in the other types, largely because serous tumours can present with extra-ovarian nonmalignant spread at the time of diagnosis. The pathological diagnosis of a borderline tumour is essentially one of dysplasia, with no (or minimal) invasion, on good histological sampling of the ovary. In the area of ovarian serous tumours, this has been further complicated by the identification of the micro-papillary subset, and of serous epithelium involving other tissues (implants—invasive versus noninvasive) and what the diagnostic criteria are and what they mean biologically......

 Why does this matter? The clinical dilemma of what do with women with a borderline ovarian tumour diagnosis is problematic in the extreme. Do these women warrant more aggressive treatment at diagnosis or can a watchful waiting policy be more appropriate? We still cannot predict which cases will/may progress with any certainty. The majority of these women are pre-menopausal, with many years of life ahead of them, and hence over-treatment may be just as harmful as under-treatment. The need for accurate pathology, and the distinction from a true low grade serous carcinoma, is vital but often very difficult. The need to exclude metastatic mucinous tumours from a primary ovarian one, even of borderline type, is well described. The questions are easy to raise, but answering them is and continues to be far harder.

The clinical implications of new insights into the origins of epithelial ovarian cancer....

open access: 
The clinical implications of new insights into the origins of epithelial ovarian cancer with emphasis on the British Columbia Ovarian Cancer Prevention Initiative - J Health Specialties

 Data from our centre showed that almost 20% of women who developed HGS cancer in our province had undergone a hysterectomy for benign disease prior to their diagnosis.

Up to 50 percent of women with advanced-stage ovarian cancer could be cured with 1 treatment model

Blogger's Note: an easier-to-read article vs. previously posted article on the same subject/author

medical news article

Are we ready for a blood test for cancer? (in research)

medical news article

What if screening for cancer was as easy as checking your cholesterol? That's the promise of techniques currently in development that may one day make it possible to detect the earliest stages of cancer with an annual blood draw.

So-called "liquid biopsies" involve extracting free-floating cancer cells or cancer DNA from the bloodstream (or in some cases from the urine) to get information about tumors too small or hidden to detect with standard techniques. This could make it possible for clinicians to remotely monitor how cancer patients are responding to treatment, to detect early warning signs of recurrence, and even to pick up the very first signs of cancer in otherwise healthy people....

"It's important to maintain healthy skepticism," Witte said, "But right now I'd say most researchers are cautiously optimistic." 

Serial Patterns of Ovarian Cancer Biomarkers in a Prediagnosis Longitudinal Dataset

open access (long/technical article)

  The area under the ROC curve for the panel of three biomarkers (CA125, HE4, and glycodelin) was higher than for CA125 alone for all analysed time groups, indicating that these markers can improve on sensitivity of CA125 alone for ovarian cancer detection.

We show that, in addition to HE4 (which has been shown to be the second best performing marker after CA125 in the context of screening), glycodelin is a novel and useful adjunct to CA125 for early detection of ovarian cancer. Glycodelin has only been previously tested in the diagnosed case control setting [11, 21], although with promising results. This work also supports previous studies showing the potential of HE4 [10–14, 16, 19], whilst suggesting that mesothelin, MMP7, and CYFRA 21-1 are not useful markers for the early detection of ovarian cancer. The next step in this work would be to validate these findings in a larger independent set and to test the potential of these candidates in multimarker longitudinal algorithms.

Veliparib for the treatment of ovarian cancer

abstract


Introduction: Ovarian cancer represents the sixth most commonly diagnosed cancer among women, with an incidence of 6.1 cases per 100.000 women and a cumulative lifetime risk of 0.5%. Treatment is based on debulking surgery and platinum-based chemotherapy, with the potential combination with taxane. However, the recently available data on the genetic basis and aetiology of ovarian cancer has led to the development of new anticancer drugs. Poly(ADP-ribose) polymerase (PARP) inhibitors are one of the most promising new classes of targeted agents currently under investigation for the treatment of ovarian cancer. Veliparib is a small molecule that inhibits both PARP-1 and PARP-2 and was originally shown to be efficacious in BRCA-associated tumors.
Areas covered: This manuscript reviews the Phase I and II studies investigating the use of veliparib in ovarian cancer. This article also provides and discusses the pharmacokinetics and pharmacodynamics of veliparib.

Expert opinion: It is still being discussed whether PARP inhibitors should be used in a front-line or relapsed setting, alone or in combination with cytotoxic chemotherapy or as maintenance treatment. In terms of veliparib, further investigations are needed to explore its full potential in ovarian cancer. It is hoped that the ongoing phase 3 trials will help to further elucidate it potential as a treatment option.

Do critical care units play a role in the management of gynaecological oncology patients? The contribution of gynaecologic oncologist in running critical care units

Do critical care units play a role in the management of gynaecological oncology patients? The contribution of gynaecologic oncologist in running critical care units

Abstract:
 Routine post-operative care in high dependency unit (HDU), surgical intensive care unit (SICU) and intensive care unit (ICU) after high-risk gynaecological oncology surgical procedures may allow for greater recognition and correct management of post-operative complications, thereby reducing long-term morbidity and mortality. On the other hand, unnecessary admissions to these units lead to increased morbidity – nosocomial infections, increased length of hospital stay and higher hospital costs. Gynaecological oncology surgeons continue to look after their patient in the HDU/SICU and have the final role in decision-making on day-to-day basis, making it important to be well versed in critical care management and ensure the best care for their patients. Post-operative monitoring and the presence of comorbid illnesses are the most common reasons for admission to the HDU/SICU. Elderly and malnutritioned patients, as well as, bowel resection, blood loss or greater fluid resuscitation during the surgery have prolonged HDU/SICU stay. Patients with ovarian cancer have a worse survival outcome than the patients with other types of gynaecological cancer. Dependency care is a part of surgical management and it should be incorporated formally into gynaecologic oncology training programme

Impact of Chemotherapy Beyond the Third Line in Patients With Recurrent Epithelial Ovarian Cancer

abstract
 

OBJECTIVES:

The goal of this study was to determine the benefit in terms of time disease control (TDC) achieved by the succession of chemotherapy beyond the third line in patients treated for recurrent epithelial ovarian cancer. Secondary objectives were to identify patients who benefited from treatments beyond 3 lines and to estimate overall survival and disease-free progression lengths.

CONCLUSIONS: These results may justify the administration of chemotherapy beyond the third line, in particular when the 2 previous lines are effective and resulted in disease control longer than 6 months.

OCRF & Ovarian Cancer National Alliance are uniting to become Ovarian Cancer Research Fund Alliance. We’re now one strong, inspiring voice!

Ovarian Cancer 

 

Join us for a Q&A with OCRFA’s leadership on February 1st at 2pm ET. OCRFA’s CEO Audra Moran and Executive Vice President Calaneet Balas will talk more about what this exciting merger means for the ovarian cancer community, and will take questions.

Register Here

Ovarian Cancer Research Fund

14 Pennsylvania Plaza
Suite 1710
New York, NY 10122

Telephone: (212) 268-1002
Fax: (212) 947-5652
Email: info@ocrf.org

Ovarian Cancer National Alliance

1101 14th Street NW
Suite 850
Washington, DC 20005

Telephone: (202) 331-1332
Toll Free: (866) 399-6262
Fax: (202) 331-2292
Email: ocna@ovariancancer.org

NCI-Molecular Analysis for Therapy Choice (NCI-MATCH) Trial - NCI

 National Cancer Institute

 The required interim analysis is well underway and a number of changes are being made to the trial at this time. We have determined that the pause on new patient enrollments needs to remain in place until all of these activities are complete. Therefore, the enrollment pause, originally expected to lift in January 2016, has been moved to April or May 2016.

Outcome of genetic evaluation of patients with kidney cancer referred for suspected hereditary cancer syndromes

abstract

Highlights

• •
  We identified several factors that may predict positive test results in patients with kidney cancer undergoing evaluation in a clinical genetics clinic. Although these risk factors have previously been associated with cancer syndromes, a need for studies of testing practices remains.
• •
  Our data suggest that in patients with kidney cancer evaluated for hereditary cancer syndromes, young age is associated with diagnosis of RCC syndromes, whereas syndromic manifestations and multiple primaries are found in Lynch syndrome.
• •
  These results, along with clinical pathway, suggested for evaluating patients with kidney cancer for inherited cancer syndrome may be useful for practicing urologists to select patients with kidney cancer to refer for genetic counseling.

ESO, CNIO and NRCO Conference on Familial Cancer

Event

 ESO, CNIO and NRCO Conference on Familial Cancer 19/05/2016 - 20/05/2016, Madrid, Spain

  MAIN TOPICS
• Breast and ovarian cancer
• Colon and prostate cancer
• Rare cancers
• Implications of applying next generation sequencing to the diagnosis

Nonhormonal Management of Menopause-associated Vasomotor Symptoms

Medscape
 Nonhormonal Management of Menopause-associated Vasomotor Symptoms: 2015 Position Statement of The North American Menopause Society

Hematuria as a Marker of Occult Urinary Tract Cancer (Patient Summary)

patient summary

Ethical and Societal Questions Loom Large as Gene Editing Moves Closer to the Clinic

JAMA Network

 The committee’s next meeting is tentatively scheduled for February 11 and 12 in Washington, DC, and it will include sessions open to the public

Hematuria as a Marker of Occult Urinary Tract Cancer (Lynch Syndrome patients)

Patients referred for AMH have a relatively lower (0.5% to 5.0%) but nontrivial probability of underlying occult cancer (2, 7–15) that is estimated to range from 7% to greater than 20% in higher-risk subgroups in some series (9, 16–18).

 The investigation of hematuria includes radiologic evaluation to identify potential pathology in the upper urinary tract.

upper urinary tract cancer:

open access
 Hematuria as a Marker of Occult Urinary Tract Cancer: Advice for High-Value Care From the American College of Physicians
 
Background: The presence of blood in the urine, or hematuria, is a common finding in clinical practice and can sometimes be a sign of occult cancer. This article describes the clinical epidemiology of hematuria and the current state of practice and science in this context and provides suggestions for clinicians evaluating patients with hematuria.
 
High-Value Care Advice 1: Clinicians should include gross hematuria in their routine review of systems and specifically ask all patients with microscopic hematuria about any history of gross hematuria.
High-Value Care Advice 2: Clinicians should not use screening urinalysis for cancer detection in asymptomatic adults.
High-Value Care Advice 3: Clinicians should confirm heme-positive results of dipstick testing with microscopic urinalysis that demonstrates 3 or more erythrocytes per high-powered field before initiating further evaluation in all asymptomatic adults.
High-Value Care Advice 4: Clinicians should refer for further urologic evaluation in all adults with gross hematuria, even if self-limited.
High-Value Care Advice 5: Clinicians should consider urology referral for cystoscopy and imaging in adults with microscopically confirmed hematuria in the absence of some demonstrable benign cause.
High-Value Care Advice 6: Clinicians should pursue evaluation of hematuria even if the patient is receiving antiplatelet or anticoagulant therapy.
High-Value Care Advice 7: Clinicians should not obtain urinary cytology or other urine-based molecular markers for bladder cancer detection in the initial evaluation of hematuria.

 Hematuria is frequently encountered among adults in ambulatory care (1, 2). Despite the absence of recommendations for hematuria screening (3, 4), millions of patients have urine dipstick testing and microscopic examinations as part of routine primary care practice (5, 6). The frequency of urinalysis with the primary intent of cancer screening is unknown; however, hematuria may often be an incidental finding on tests pursued for other purposes, given the multiplex nature of dipstick tests. Referral series underscore the potential for a positive test result to be the presenting sign of occult cancer, and existing hematuria guidelines emphasize structured urologic investigation related to this risk with endoscopy of the bladder (cystoscopy), imaging, and potentially other diagnostic tests and procedures. However, the magnitude of the risk for underlying cancer varies greatly (7–9), and the quality of evidence informing practice creates uncertainty......

 Hematuria occasionally has a dramatic presentation as grossly visible blood in the urine. Symptomatic gross hematuria with associated flank pain or renal colic is the classic presentation of urinary stone disease, whereas painless gross hematuria has a stronger association with cancer......