abstract: [Clinical aspects of familial ovarian cancer - current status and issues in Japan] (focus on brca)

Blogger's Note: the [ ] indicates translated version


[Clinical aspects of familial ovarian cancer - current status and issues in Japan]

Abstract
Familial ovarian cancer occurs as part of two genetically distinct syndromes: hereditary breast and ovarian cancer(HBOC) and hereditary nonpolyposis colorectal cancer(HNPCC) (Lynch Syndrome) .

HBOC caused by inherited mutations of BRCA1/2 and HNPCC caused by mismatch-repair genes are considered responsible for about 65 to 75% and 10 to 15% of familial ovarian cancers, respectively. Germline mutations of BRCA1 are considered responsible for about 50% of ovarian cancer families and 80% of breast-ovarian cancer families. BRCA2 mutations are less common than BRCA1 mutations in ovarian cancer families. A high proportion of serous adenocarcinomas at an advanced stage has been reported with BRCA-related ovarian cancers in several studies. It is controversial whether BRCA-related ovarian cancer patients carry a better prognosis despite the aggressive tumor-pathological characteristics of their disease, compared to sporadic cases. However, a good therapeutic response may be attributable to platinum-based chemotherapy. Recently in Japan, gene testing of BRCA1/2 has been available as a routine clinical test for diagnosing ovarian cancer families. Because the mutation spectrum of BRCA1/2 in Japanese was different from that of non-Ashkenazi individuals, the clinical application of BRCA1/2 gene testing for Japanese has been advocated. Approximately 1-5% of ovarian cancer pa-tients in Japan are thought to have a family history of breast and/or ovarian cancer. The prevalence of deleterious mutations of BRCA1/2 in Japanese was reportedly significantly higher than that of non-Ashkenazi individuals despite the low frequency of familial cases in Japan. Although the age at diagnosis of ovarian cancers with BRCA1/2 mutation in the United States was earlier than those of the sporadic cases, there were no differences among Japanese. These results suggest that clinical and genetic aspects of BRCA-related ovarian cancer of the Japanese are different from those of Caucasians.

A serious issue in this field is how the results will lead to a basis for the clinical application of a cancer prevention strategy targeting BRCA mutation carriers in Japanese.

High-Risk Ovarian Cancer Based on 126-Gene Expression Signature Is Uniquely Characterized by Downregulation of Antigen Presentation Pathway - Japan

Abstract

Purpose: 

High-grade serous ovarian cancers are heterogeneous not only in terms of clinical outcome but also at the molecular level. Our aim was to establish a novel risk classification system based on a gene expression signature for predicting overall survival, leading to suggesting novel therapeutic strategies for high-risk patients. 

Experimental Design: 

In this large-scale cross-platform study of six microarray data sets consisting of 1,054 ovarian cancer patients, we developed a gene expression signature for predicting overall survival by applying elastic net and 10-fold cross-validation to a Japanese data set A (n = 260) and evaluated the signature in five other data sets. Subsequently, we investigated differences in the biological characteristics between high- and low-risk ovarian cancer groups. 

Results: 

An elastic net analysis identified a 126-gene expression signature for predicting overall survival in patients with ovarian cancer using the Japanese data set A (multivariate analysis, P = 4 × 10⁻²⁰).. ........ Through gene ontology and pathway analyses, we identified a significant reduction in expression of immune-response–related genes, especially on the antigen presentation pathway, in high-risk ovarian cancer patients. 

Conclusions: 

This risk classification based on the 126-gene expression signature is an accurate predictor of clinical outcome in patients with advanced stage high-grade serous ovarian cancer and has the potential to develop new therapeutic strategies for high-grade serous ovarian cancer patients. 

abstract: Histology-specific long-term trends in the incidence of ovarian cancer and borderline tumor in Japanese females: A population-based study from 1983 to 2007

 Blogger's Views:
there are a number of interesting subjects here - Japan appears historically to have a higher rate of clear cell than other nations; Japan has also studied clear cell ovarian cancer more extensively than elsewhere (for obvious reasons); increasing incidence rates observed in the Japanese population seems to be contrary to other nation's research (eg. stable/declining incidence rates) however the key is in the data compliation (eg. exclusion of LMP; peritoneal cancers), it can be noted however that there has been reported in the North America's that ovarian cancer rates have been increasing but for some unknown (or unpopular?) reason less is known about the reasons for these discrepancies; past blogs have been posted about increasing incident rates; it is unfortunate that this paper is not open access

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Histology-specific long-term trends in the incidence of ovarian cancer and borderline tumor in Japanese females: A population-based study from 1983 to 2007 in Niigata:

Abstract

Aim: 
The histology-specific long-term trends in the incidence of ovarian cancer and borderline tumors in Japanese women were examined, based on data from the population-based cancer registry in Niigata, Japan.

Material and Methods: 
Data were obtained from the Niigata Gynecological Cancer Registry, which covered the entire female population in Niigata prefecture, Japan, during the period from 1983 to 2007.

Results: 
A total of 3134 females with epithelial ovarian cancer, including borderline tumor cases, were diagnosed between 1983 and 2007. The age-standardized rates (ASRs) of both ovarian cancer and borderline tumors have steadily increased, with significant changes in ovarian cancer in all age groups, and borderline ovarian tumors in subjects aged <50. The ASRs of endometrioid adenocarcinoma showed a steady increasing trend, and those of clear cell and mucinous adenocarcinomas showed significant increasing trends in the total population. The ASRs of clear cell, mucinous, and endometrioid adenocarcinomas in the 50+ age group were significantly increased, especially the incidence of clear cell adenocarcinoma, which strikingly increased by approximately threefold from 1.2 (1983–1989) to 3.5 (2000–2007) per 100 000 females.

Conclusion: 
This prefecture-wide study showed the practical trends in ovarian cancer and borderline tumors in Japanese females. The incidence of ovarian cancer has steadily increased, with significant increases in the incidence of clear cell and mucinous adenocarcinomas in the total population during the past two decades. Because of the poor response rate of these histological subtypes to platinum-based regimens, novel treatment approaches should be adopted to improve the prognostic outcome in patients with ovarian cancer in Japan.

abstract: Incidence of metachronous second primary cancers in Osaka, Japan: update of analyses using population-based cancer registry data

Incidence of metachronous second primary cancers in Osaka, Japan: update of analyses using population-based cancer registry data:

(define: metachronous - Two or more cancers appearing at different points in time.)

Summary

Cancer survivors are at excess risk of developing second primary cancers, but the level of risk is uncertain in Japan.

To investigate the risk of survivors developing second primary cancers, we conducted a retrospective cohort study using data from the Osaka Cancer Registry. Study subjects were all reported cases aged 0-79, who were first diagnosed with cancer between 1985 and 2004 in Osaka and survived for at least 3 months, followed up through December 2005.

A metachronous second primary cancer was defined as any invasive second cancer which was diagnosed between 3 months and 10 years after the first cancer diagnosis.

The main outcome measures were incidence rates per 100,000 person-years, cumulative risk and standardized incidence ratios (SIRs) of second primary cancer. Metachronous second primary cancers developed in 13,385 (3.8%) out of 355,966 survivors after a median follow-up of 2.5 years. Sex-specific incidence rates of metachronous second primary cancer per 100,000 person-years increased with age, and were higher among males than females (except for age 0-49), but these rates did not differ over the study period. The 10-year cumulative risk was estimated as 13.0% for those who first developed cancer in their sixties (16.2% for men, 8.6% for women). The SIRs among those with first cancer at 0-39 years old and 40-49 years old were 2.13 and 1.52, respectively, in both sexes, while the SIRs among cancers of the mouth/pharynx, esophagus and larynx were much higher than one as for site relationships.

We showed that cancer survivors in Osaka, Japan, were at higher risk of second primary cancers compared to the general population. Our findings indicated that second primary cancers should be considered as a commonly encountered, major medical problem. Further study is required to advance our understanding for effective measures against multiple primary cancers.

© 2012 Japanese Cancer Association

ASCO 2011 abstract: A North American population-based outcome for early-stage ovarian clear cell (stages 1-11) carcinoma (OCCC). - ASCO 2011 (including w/wo irradiation)

Abstract:

Background: OCCC is regarded as having a poor outcome and being relatively treatment resistant. Recent Japanese data instead have demonstrated high survival in early stage and radiation sensitivity. This study was carried out to reproduce/refute these findings in a North American setting.

Methods: Women with OCCC who had attended one of the four British Columbia Cancer Agency (BCCA) centers have staging, pathological, treatment, and outcome data recorded in a computerized database. Irradiation (XRT) plus platin-based chemotherapy was the standard treatment. XRT usage mandated all such women provincially attending a BCCA centre. However, individual physicians within BCCA differed in their uptake of XRT. Outcomes with or without XRT could be compared. Univariate and multivariate (decision-tree analysis) analyses for disease-free survival (DFS) were performed.

Results: 241 Stage I-II women attended between January 2000 and December 2008 (IA/IB n=64; Ic n=147; II n=30). 5 year and 10 year DFS for stage IA/B; IC and II were 85 and 70%; 64 and 58%; and 43 and 43% respectively. IC subsets faired differently: rupture alone (spontaneous and surgical were equivalent) - 5 yr DFS 80% versus 34% if cytologically positive and 43% with surface involvement. Decision-tree analysis identified cytologic positivity as the most important factor (recurrence 27% if negative, 72% if positive). Surface involvement then further subdivided the cytologically positive: surface involved 93% recurrence, if not involved 60%. XRT had no effect in stage IA (85% DFS at 5 yrs with or without it) but was superior to chemotherapy alone in IC (5 yr DFS 68% vs 58%, 10 yr DFS 63% vs 52%, HR 0.59).
Conclusions: Stage IA OCCC has an excellent long-term outcome as does IC (rupture only). IC otherwise has a poor outcome as does stage II. XRT and chemotherapy improves outcome in stage IC versus chemotherapy alone.

abstract: A survey of the perspectives of patients who are seriously ill regarding end-of-life decisions in some medical institutions of Korea, China and Japan

Purpose
"The debate about the end-of-life care decision is becoming a serious ethical and legal concern in the Far-Eastern countries of Korea, China and Japan. However, the issues regarding end-of-life care will reflect the cultural background, current medical practices and socioeconomic conditions of the countries, which are different from Western countries and between each other. Understanding the genuine thoughts of patients who are critically ill is the first step in confronting the issues, and a comparative descriptive study of these perspectives was conducted by collaboration between researchers in all three countries....."

Multinational Comparisons of Health Systems Data, 2011 - The Commonwealth Fund including link to 2011 patient care coordination (11 countries)

"International comparisons of health care systems offer valuable tools to health ministers, policymakers, and academics wishing to evaluate the performance of their country's system. In this chartbook, we use data collected by the Organization for Economic Cooperation and Development (OECD) to compare health care systems and performance on a range of topics, including spending, hospitals, physicians, pharmaceuticals, prevention, mortality, quality of care, and prices. We present data across several industrialized countries: Australia, Canada, Denmark, France, Germany, Japan, the Netherlands, New Zealand, Norway, Sweden, Switzerland, the United Kingdom, and the United States. Whenever possible, we also present the median value of all 34 members of the OECD.......

Downloads

• Chartbook (248K PDF)
• • Chartbook (626K PPT) 

    Related

    • In the Literature
      • New 2011 Survey of Patients with Complex Care Needs in Eleven Countries Finds That Care Is Often Poorly Coordinated

Validation of the Histologic Grading for Ovarian Clear Cell Adenocarcinoma: A Retrospective Multi-institutional Study by the Japan Clear Cell Carcinoma Study Group

Abstract
"Pathologic slides from 150 patients with clear cell adenocarcinoma from the collaborating institutions were reviewed independently by 2 pathologists, and each tumor was graded histologically using the Shimizu-Silverberg and International Federation of Gynecology and Obstetrics (FIGO) grading systems...................... These results suggest that the 2 tested grading systems have limited value for the prognostication of patients with clear cell adenocarcinoma, and that a more effective grading system for this tumor may be required."

WHO | World Health Organization - radiation information/FAQ

WHO warns against self-medicating against radiation

17 March 2011 -- WHO is cautioning people concerned about the radiation issues in Japan against self-medicating with potassium iodide or taking products containing iodine. The advice follows reports of people using these substances in response to radiation leaks from nuclear plants in Japan. Potassium iodide should only be taken when there is a clear public health recommendation to do so.

• FAQs: Japan nuclear concerns
• More on the crisis in Japan

(NCCN) Updated Ovarian Cancer Guidelines Offer a New Treatment Choice

Note: this refers to the Japanese study published 2010 of weekly Taxol - search blog for the original study and additional commentaries


March 14, 2011 — The updated 2011 National Comprehensive Cancer Network (NCCN) Ovarian Cancer Guidelines have added a new treatment option — dose-dense paclitaxel — for the first-line treatment of stage II, III, or IV epithelial ovarian cancer.

The category 1 recommendation comes from data from the Japanese Gynecologic Oncology Group, said panel chair Robert J. Morgan, MD, professor of medicine at the City of Hope Comprehensive Cancer Center in Duarte, California, here at the NCCN 16th Annual Conference.

In a phase 3 open-label randomized controlled trial published in the Lancet (2009; 374:1331-1338), Noriyuki Katsumata and colleagues reported that dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer resulted in a significant survival advantage. The study concluded that paclitaxel and carboplatin given every 3 weeks is standard treatment for advanced ovarian carcinoma.

"This was an important addition," Dr. Morgan told Medscape Medical News........"

ABC News - Japan Earthquake: before and after photos (google earth)

Sun Mar 13, 2011 3:00pm AEDT

Aerial photos taken over Japan have revealed the scale of devastation across dozens of suburbs and tens of thousands of homes and businesses.
Hover over each satellite photo to view the devastation caused by the earthquake and tsunami.

Takeda Pharma, Millennium commence (AMG386) TRINOVA-1 Phase III cancer (ovarian) trial

Takeda Pharmaceutical and the Takeda Oncology Company: Millennium, have commenced TRINOVA-1 Phase III clinical trial on anti-cancer agent AMG 386 in Japan

Review and revision of guidelines for ovarian cancer in Japan (abstract)

A survey of members of the Japan Society of Gynecologic Oncology revealed that 93% of the members use the present Guideline for Ovarian Cancer Treatment in practice.

commentary/Japanese study - Carbo/Taxol - Dose-Dense Chemotherapy for Ovarian Cancer - National Cancer Institute

"...Women with advanced ovarian cancer lived longer and without their tumors growing after receiving a modified regimen of a standard chemotherapy drug combination, Japanese researchers have reported. In a large phase III clinical trial, the researchers randomly assigned women to receive six cycles of carboplatin and paclitaxel (Taxol) every 3 weeks (standard regimen) or six cycles of carboplatin every 3 weeks and a lower dose of paclitaxel (Taxol) once a week (dose-dense regimen). Women in the dose-dense group had a 29 percent reduction in the risk of progression and a 25 percent reduction in the risk of death after 3 years of follow-up. The results were published online September 18, 2009, in The Lancet (see the journal abstract).
Although the dose-dense regimen had more toxic effects than the standard regimen, survival benefits of this magnitude "have been rare in women with advanced ovarian cancer," wrote. Noriyuki Katsumata, M.D., and colleagues from the Japanese Gynecologic Oncology Group (JGOG).
The results, explained Ted Trimble, M.D., M.P.H., from NCI's Division of Cancer Treatment and Diagnosis, are consistent with what has been seen in breast cancer using a dose-dense chemotherapy regimen. The idea, he continued, is "to balance efficacy and toxicity by using a weekly schedule rather than every 3 weeks."...."