the Oncologist: Relentless Progress: ASCO Responds

Blogger's Note: the 'timeline' section includes stats on ovarian cancer

Relentless Progress: ASCO Responds
ALLEN S. LICHTER
American Society of Clinical Oncology, Alexandria, Virginia, USA

Dr. Beatty’s thoughtful piece [1] brings up a number of important
points. Progress against cancer has been relentless. To
summarize these advances, the American Society of Clinical
Oncology (ASCO) has created a website:

CancerProgress.net.http://www.cancerprogress.net/
 




It’s a summary of important milestones in each cancer and
each treatment modality, concentrating on the 40 years since
the signing of the National Cancer Act in 1971......

Cruciferous vegetables and cancer risk in a network of case–control studies

Background: Cruciferous vegetables have been suggested to protect against various cancers, though the issue is open to discussion. To further understand their role, we analyzed data from a network of case–control studies conducted in Italy and Switzerland.
Results: The multivariate odds ratio (OR) for consumption of cruciferous vegetables at least once a week as compared with no/occasional consumption was significantly reduced for cancer of the oral cavity/pharynx (OR = 0.83), esophagus (OR = 0.72), colorectum (OR = 0.83), breast (OR = 0.83), and kidney (OR = 0.68). The OR was below unity, but not significant, for stomach (OR = 0.90), liver (OR = 0.72), pancreatic (OR = 0.90), laryngeal (OR = 0.84), endometrial (OR = 0.93), ovarian (OR = 0.91), and prostate (OR = 0.87) cancer.

Conclusion: This large series of studies provides additional evidence of a favorable effect of cruciferous vegetables on several common cancers.

financial press release: Halt Medical, Inc. Calif., Feb. 11, 2012 (uterine fibroid technology) + link to clinical trial

Blogger's Note: uterine fibroids affects many women worldwide and can be the cause of a misdiagnosis in ovarian cancer (benign/malignancy); so of interest generally to women




About Halt Medical, Inc.
Founded in 2004, Halt Medical is a medical device company focused on women's health. The company has developed a procedure and related equipment for treating uterine fibroids that is less expensive, more effective and less invasive than other alternatives - the Halt GFA System. In June 2010, the U.S. Food and Drug Administration cleared the Halt 2000GI™ Electrosurgical System for soft tissue ablation using radiofrequency energy. The results of Halt Medical's international studies have led to recent approvals for treating uterine fibroids in Canada and the European Union. The Halt System may be used for general surgical use in the U.S. The company recently completed a 137 patient IDE clinical trial at 11 sites in 3 countries to demonstrate clinical safety and efficacy in the treatment of symptomatic uterine fibroids. FDA clearance is expected this year. The Company is located in Livermore, CA.
Information about the Halt Fibroid Study and a list of clinical sites in the U.S. may be found at www.clinicaltrials.gov, study number NCT00874029.

open access: Cytoreductive Surgery Combined with Hyperthermic Intraperitoneal Intraoperative Chemotherapy in the Treatment of Advanced Epithelial Ovarian Cancer

 Background/Aims.
Intraperitoneal intraoperative hyperthermic chemotherapy (HIPEC) has been used in the treatment of ovarian cancer. The purpose of the study is to determine the efficacy of HIPEC after cytoreductive surgery in advanced ovarian cancer

 From 2006 to 2010, 43 women with primary or recurrent ovarian cancer were enrolled in the study and underwent maximal cytoreductive surgery and HIPEC. The mean age of the patients was 59.9 yrs (16–82) years.

Table 1: Characteristics of the patients.

Table 2: Peritonectomy procedures.

Table 3: Complications ( 6 grade 111/1V events)
"...Severe morbidity (grade 3 and 4) has been recorded in 6 patients (14%). It is obvious that the most severe complication is the anastomotic failure. Anastomotic failure has been reported in other series as the most frequent complication [8, 9, 25]. Cisplatin has been incriminated to impair anastomotic healing in animal studies [26] in contrast to local hyperthermia that has not [27]. As a consequence, the failures may be attributed either to cisplatin or to the immediate restoration of the gastrointestinal tract after low-anterior resection particularly in those cases with preoperative partial intestinal obstruction. The importance of intestinal obstruction and the avoidance of immediate restoration of the gastrointestinal tract has been emphasized [9] resulting in significant decrease of anastomotic failures [28]. Therefore a protective colostomy seems to be a reasonable solution. Other severe complications as intra-abdominal abscess or sepsis or postoperative bleeding are infrequent [8, 9, 25]....."


Conclusions
Maximal cytoreductive surgery with standard peritonectomy procedures combined with intraperitoneal chemotherapy is a well-tolerated and feasible method for treatment of advanced epithelial ovarian cancer. It appears to improve long-term survival securing that complete or near complete cytoreduction is possible in the vast majority as well as the eradication of the microscopic residual tumor.

Molecular profiling reveals differences between primary and recurrent ovarian cancers | Science Codex - Clearity Foundation

How long before CVac, a new treatment for ovarian cancer, is available in the UK? – Telegraph Blogs

"Since my blog post about the Stage 3 trial of CVac – a new treatment for ovarian cancer – I have been in contact with Dr Neil Frazer, who is heading this research for the Australian company Prima Biomed. He has answered my questions about the treatment, clarified the methodology and explained about Prima Biodmed's medical facility in Dubai where CVac will be supplied......

to open April - Concerned about ovarian cancer? Visit one of the DOVE clinics - media

Blogger's Note: the cost is not apparent nor availability to Quebec residents only or ?

MONTREAL - Of the 12 new DOVE clinics to open in the Montreal area as of April, the Anjou clinic is already up and running.

No referral is needed. Women age 50 and older with any symptoms – bloating, pelvic or abdominal pain, frequent urination, difficulty eating or feeling full quickly – lasting longer than two weeks but less than a year, are encouraged to go for testing.

Satellite Centre 1 — Clinique médicale du Haut Anjou, 7500 Galeries d’Anjou Blvd. 514-493-1999

Satellite Centre 2 — Clinique Familiale Pas-à-Pas, 3650 Henri Bourassa Blvd. E. 514-328-9797

Satellite Centre 3 — 8260 Maurice Duplessis Blvd. 514-643-1113

Satellite Centre 4 — Polyclinique Cabrini, 5700 St. Zotique St. E. 514-253-6776

Satellite Centre 5 — Clinique Perrier, 10749 Lajeunesse St. 514-383-0559

Satellite Centre 6 — Clinique Plein Ciel, 475 Côte Vertu Blvd. 514-337-3171

Satellite Centre 7 — Lakeshore General Hospital, 160 Stillview Rd., Pointe Claire 514-630-2225

Satellite Centre 8 — Cavendish Medical Centre Inc., 2545 Cavendish Blvd. 514-483-2424

Satellite Centre 9 — Lachine Hospital, 650 16th Ave., 514-934-1934, Local 77306

Satellite Centre 10 — Sacré Coeur Hospital, 5400 Gouin Blvd. W. 514-338-2222, Local 2063

Satellite Centre 11 — Queen Elizabeth Health Complex, 2100 Marlowe Ave. 514-699-4630

Satellite Centre 12 — St. Henri Medical Centre, 3966 Notre Dame St. W. 514-935-4330

Read more: http://www.montrealgazette.com/Concerned+about+ovarian+cancer+Visit+DOVE+clinics/6129807/story.html#ixzz1m0yVCBfu

abstract: No place like the hospital. [J Pain Symptom Manage

Source

Harvard Pilgrim Health Care Institute, Boston, Massachusetts 02215, USA. mgillick@partners.org

Abstract

The gold standard for end-of-life care is home hospice. A case is presented in which a patient dying of irreversible small bowel obstruction from metastatic cancer insisted on remaining in the acute care hospital for care when alternative sites of care, including a skilled nursing facility and residential hospice, were available to her and covered by her health insurance plan. The ethical issues raised by this case are discussed from the perspective of the patient, the clinical team, the hospital, and the insurance company. Over the past decade, hospital-based palliative care consultation and general inpatient hospice care have sought to improve the quality of dying in the hospital. To the extent that such efforts have been successful, they may result in increasing demand for the hospital as the site for terminal care in the future.

Drugs, Herbs and Supplements: MedlinePlus (alpha list)

FYI: top 5 most read items this week - Ovarian Cancer and Us Blog

Results of post-operative abdomino-pelvic radiotherapy Nov 3, 2008 original date posted

youtube video: "Do You See Politics on My Chest" Feb 5, 2012  original date posted

open access: Participatory Medicine: Must You Be Rich Feb 2, 2012 original date posted

JCO - open access - It Takes a Village (palliative care) Feb 8, 2012 original date posted

She the People - Komen, go back to your roots by Donna Trussell Feb 5, 2012 original date posted

(very short) abstract: A Surveillance Conundrum: A Case of 4 Distinct Primary Malignancies in a BRCA-1 Mutation Carrier - Intl Jnl Gyn Pathology

Abstract

Women with HBOC syndrome present a unique challenge to the oncology community, as will many genetic cancer syndromes yet to be discovered as genetic testing increases in availability. Issues of management and, most importantly, implication are yet to be elucidated. After a diagnosis of epithelial ovarian carcinoma lifelong follow-up is recommended. Given the high recurrence rate and dismal long term prognosis of advanced epithelial ovarian carcinoma this recommendation is more often than not moot. There are no clear guidelines or recommendations for surveillance designed for women with disease free survival greater than five years. This case presents a unique scenario of a woman with predictable disease that remains unpreventable.

abstract: Histological Grading of Ovarian Clear Cell Adenocarcinoma: Proposal for a Simple and Reproducible Grouping System - Intl Jnl Gyn Pathology

Blogger's Note: 'interesting' stat ranges between early/advanced clear cell ovarian cancers; read full abstract for more details (full access requires subscription $$$); some details deleted for ease of reading 

Abstract

"In this study, we aimed to develop a histological grading system for ovarian clear cell adenocarcinoma (CCA), based on the tumor growth architectures."

"The interobserver reproducibility and prognostic value of the assigned groups were analyzed for 159 CCAs from 5 institutions."

"In early-stage cases [International Federation of Gynecology and Obstetrics (FIGO) stage I–II], .....(survival rates 56-100%)

"In advanced cases (FIGO stage III–IV),.....(survival rates 16-52%)

"The proposed grouping system could divide patients with CCA into 3 subgroups with distinct prognostic indications, providing a 3-tier histological grading system for ovarian CCA."

abstract: A Systematic Review of Papers Examining the Use of Intraoperative Frozen Section in Predicting the Final Diagnosis of Ovarian Lesions Intl Jnl Gyn Pathology (clear cell, mucinous, borderline, invasive...)

Abstract

"This systematic review assesses the accuracy of the frozen section classification of benign and borderline lesions or invasive carcinoma when compared with the final diagnosis on paraffin section. A Pubmed database search identified 18 retrospective cohort studies, published since 2005 that satisfied the criteria, on the critical appraisal sheet of the center for evidence-based medicine, The University of Oxford.

The sensitivity, specificity, and negative and positive predictive values suggest that frozen section is more accurate at discriminating between benign lesions and invasive carcinoma than between benign and borderline or borderline lesions and invasive carcinoma and indicate a tendency to overcall benign tumors as borderline and borderline tumors as invasive malignancies.
A narrative review of individual papers and abstracts suggests that this particular difficulty is encountered when dealing with clear cell carcinoma and mucinous lesions of all sorts.
This may have greater importance in the future with the introduction of targeted chemotherapy requiring accurate typing to guide the use of genetic analysis. It would be beneficial if future researchers comparing the results of frozen section and paraffin sections presented their results in the context of preoperative assessment of the clinical and radiological findings or the intraoperative appearances of the tumor and abdominal cavity, which would allow the identification of those cases in which the frozen section allowed a refinement of the diagnoses made using these modalities."

abstract: Frequency of Serous Tubal Intraepithelial Carcinoma in Various Gynecologic Malignancies: A Study of 300 Consecutive Cases

Abstract:

Serous tubal intraepithelial carcinoma (STIC) has been implicated in the pathogenesis of pelvic serous carcinoma. We hypothesized that, if this is the case, the frequency of STIC should be substantially lower in endometrial serous carcinomas, in nonserous gynecologic malignancies, and in benign gynecologic neoplasms than in ovarian or peritoneal serous carcinomas.

From 2007 to 2009 the fallopian tubes of 342 consecutive gynecologic cases were entirely submitted for histology using the Sectioning and Extensively Examining the FIMbriated end protocol.

This study included 300 of these cases (277 TAH-BSO, 23 BSO) after exclusion. The hematoxylin and eosin-stained slides from the fallopian tubes were independently reviewed by 2 gynecologic pathologists who were blinded to all other findings; disagreements were resolved by a third pathologist.

Among 46 cases of ovarian malignancies, STIC was identified in 6 (18.8%) of 32 cases of serous carcinoma, but not in any other subtype. Similarly, STIC coexisted in 4 (14.3%) of 28 cases of endometrial serous carcinoma; however, no STIC was identified in any of the 74 cases of nonserous endometrial malignancies. STIC was identified in 2 (28.6%) of 7 cases of peritoneal serous carcinoma.

No STIC was identified among 15 nongynecologic malignancies, 90 cases of benign conditions, and 27 cases of other conditions including 4 cases of cervical adenocarcinoma in situ and high-grade cervical intraepithelial lesions, 8 cases of endometrial atypical complex hyperplasias, and 15 cases of ovarian borderline tumors.

In conclusion, the fallopian tube may be the origin of some pelvic serous carcinomas. Other possibilities that may explain the origin of pelvic high-grade serous carcinoma are discussed. Given that STIC coexisted with 14% of endometrial serous carcinomas, a more unifying theory may be that gynecologic serous carcinomas and STIC are multifocal lesions.

abstract: (Avastin) Bevacizumab-Associated Fistula Formation in Postoperative Colorectal Cancer Patients - adverse events

Blogger's Note: adverse events are worth noting albeit other types of cancers; full text of paper would be required to properly assess the conclusions of this particular study

           ~~~~~~~~~~~~~~~~~~~~

Conclusions

Bevacizumab is the most common antiangiogenesis agent used for treatment of metastatic CRC. Previous adverse events associated with bevacizumab treatment include venous thromboembolism, poor wound healing, and spontaneous bowel perforation. In this report, late postoperative development of fistulas occurred relatively soon after initiation of bevacizumab and usually spontaneously resolved with cessation of bevacizumab treatment. Based on the timing of fistula development relative to operation and initiation of bevacizumab, fistulas are likely secondary to bevacizumab therapy rather than postsurgical complications. Bevacizumab-induced fistulas occur in a small, but significant proportion of CRC patients and must be recognized early.

2012 Recently updated NCCN Clinical Practice Guidelines in Oncology™ plus link to Ovarian Cancer (and other related) NCCN guidelines

Blogger's Note: Lynch Syndrome is included in the Colorectal Cancer section (*see below)

NCCN Guidelines for Treatment of Cancer by Site

• Bone Cancer Version 2.2012
• Breast Cancer Version 1.2012
• Colon Cancer Version 3.2012
• Hodgkin Lymphoma Version 1.2012
• Non-Hodgkin's Lymphomas Version 1.2012
• Rectal Cancer Version 3.2012
• Testicular Cancer Version 1.2012
• Waldenström's Macroglobulinemia / Lymphoplasmacytic Lymphoma Version 1.2012
• Cancer Related Fatigue (and others)

NCCN Guidelines for Supportive Care

• Distress Management Version 1.2012

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

NCCN Guidelines for Treatment of Cancer by Site (professional)

You must Login or Register to access this information.

Occult Primary (Cancer of Unknown Primary)

Ovarian Cancer

• Epithelial Ovarian Cancer (including Fallopian Tube Cancer and Primary Peritoneal Cancer)
• Borderline Epithelial Ovarian Cancer (Low Malignant Potential)
• Less Common Ovarian Histologies

Fallopian Tube Cancer (See Ovarian Cancer)

Primary Peritoneal Cancer (See Ovarian Cancer) 

          ~~~~~~~~~~~~~~~~~~~~~

---

NCCN Guidelines for Detection, Prevention, &  Risk Reduction (*includes genetic syndromes, supportive care):

---

Colorectal Cancer Screening

Genetic/Familial High-Risk Assessment: Breast and Ovarian

• Breast and/or Ovarian Genetic Assessment
• Hereditary Breast and/or Ovarian Cancer
• Li-Fraumeni Syndrome
• Cowden Syndrome

Fasting Plus Chemo May Help in Cancer Fight - MedicineNet - research in mice

Blogger's Note: note that this research was done in mice

"We don't know whether in humans it's effective," Longo said. "It should be off limits to patients, but a patient should be able to go to their oncologist and say, 'What about fasting with chemotherapy or without' if chemotherapy was not recommended or considered?"
The researchers warned that fasting may not be safe for all cancer patients, particularly those who have already lost a significant amount of weight or have other conditions, such as diabetes. They added that fasting can cause headaches and a drop in blood pressure. The study also pointed out that cancer-free survival resulting from fasting may not extend to large tumors.
According to the American Cancer Society, "available scientific evidence does not support claims that fasting is effective for preventing or treating cancer. Even a short-term fast can have negative health effects, while fasting for a longer time could cause serious health problems."

abstract: Adapted ice cream as a nutritional supplement in cancer patients: impact on quality of life and nutritional status

Conclusions

The administration of ice cream could cover, in part, the social aspect of food and improve QLQ in malnourished cancer patients. These results are encouraging and deserve further confirmation.

open access: BMC Cancer - Predictive models for mutations in mismatch repair genes: implication for genetic counseling in developing countries (Lynch Syndrome)

 Background

Lynch syndrome (LS) is the most common form of inherited predisposition to colorectal cancer (CRC), accounting for 2–5% of all CRC. LS is an autosomal dominant disease characterized by mutations in the mismatch repair genes mutL homolog 1 (MLH1), mutS
homolog 2 (MSH2), postmeiotic segregation increased 1 (PMS1), post-meiotic segregation increased 2 (PMS2) and mutS homolog 6 (MSH6). Mutation risk prediction models can be incorporated into clinical practice, facilitating the decision-making process and identifying
individuals for molecular investigation. This is extremely important in countries with limited economic resources. This study aims to evaluate sensitivity and specificity of five predictive models for germline mutations in repair genes in a sample of individuals with suspected
Lynch syndrome.

"Lynch syndrome (LS) is the most common form of inherited predisposition to colorectal cancer (CRC), accounting for 2–5% of all CRC [1]. Colorectal cancer in LS differs from sporadic cases by an earlier age of diagnosis (mean age approximately 44 years), a predominance of proximally-sited colon cancers (60–70%) and an increased propensity to
synchronous or metachronous CRCs (25%) [2,3]. Individuals with LS have an 80% probability of developing CRC at 65 years, and they are at an elevated risk of developing a second primary CRC [4] as well as at an increased risk for extra-colonic malignancies, including endometrial, gastric, small bowel, urological tract, ovary, pancreas and brain cancer
[5]."

 Conclusions

The Barnetson, PREMM, MMRpro and Wijnen models present similar AUC. The AUC of the Myriad model is statistically inferior to the four other models. 

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

open access PLoS ONE: Health Risk or Resource? Gradual and Independent Association between Self-Rated Health and Mortality Persists Over 30 Years

Wiki:  
 Salutogenesis is a term coined by Aaron Antonovsky,^[1] a professor of medical sociology. The term describes an approach focusing on factors that support human health and well-being, rather than on factors that cause disease. More specifically, the "salutogenic model" is concerned with the relationship between health, stress, and coping.
Antonovsky's theories reject the "traditional medical-model dichotomy separating health and illness". He described the relationship as a continuous variable, what he called the "health-ease versus dis-ease continuum".^[1]

~~~~~~~~~~~~~~~~~~~~~~~~~~~~

 Background

Poor self-rated health (SRH) is associated with increased mortality. However, most studies only adjust for few health risk factors and/or do not analyse whether this association is consistent also for intermediate categories of SRH and for follow-up periods exceeding 5–10 years. This study examined whether the SRH-mortality association remained significant 30 years after assessment when adjusting for a wide range of known clinical, behavioural and socio-demographic risk factors.

Conclusions

SRH (self reported health) is a strong and “dose-dependent” predictor of mortality. The association was largely independent from covariates and remained significant after decades. This suggests that SRH provides relevant and sustained health information beyond classical risk factors or medical history and reflects salutogenetic rather than pathogenetic pathways.

Feb 9th: The Maze of PARP Inhibitors in Ovarian Cancer - Cancer Network

Blogger's Note:  full access, free subscription

Conclusion

"While consideration of chemoprevention with PARP inhibitors is on the horizon, many knowledge gaps exist regarding these agents. Although the trials in EOC provided some answers regarding the activity of PARP inhibitors, they raised many other questions. These questions may actually complicate the picture as newer agents in this drug class make their way to the clinical arena. A collaborative approach among the researchers is needed to systematically answer these questions so we are better equipped to provide effective treatment to the BRCA-deficient patients. It is noteworthy that The Cancer Genome Atlas Group analysis did reveal other commonly deregulated pathways in this disease—such as RB, RAS/PI3K, FOXM1, and NOTCH—that might provide future opportunities for therapeutic targeting while the story of the PARP inhibitors continues to unfold."


 

Medical News:Cancer Treatment OK During Pregnancy - in OB/Gyn, Pregnancy from MedPage Today

media: Fast-track testing helps to find ovarian cancer early (relates to Dove Report/see comment 'pelvic cancer')

Blogger's Note:

this media report relates directly to the Dove Report published (and commentary) in the Lancet Oncology Jan 17th;

search this blog and/or direct link  to the Lancet: http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2811%2970405-3/fulltext

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

" (Dr) Gilbert is also campaigning to change the name of ovarian cancer to "pelvic cancer."
Research over the last decade has shown that most cases of ovarian cancer don't actually begin in the ovaries at all, but in the fallopian tubes. Pre-cancerous cells grow in the tubes and then shed over the surface of the ovaries, where they cause tumours.
By the time the cancer is found in the ovaries, it's already advanced. She says the focus should be on finding the cancer in its earliest stage in the tubes.
"We, for so many years, [kept] looking at the wrong place," she told reporters Thursday.
"Put bluntly, we had the name wrong, the staging wrong, and the diagnostic testing wrong. It is no wonder we have lost so many lives to this disease.""

media: (re: Lancet report) Current trend is to preserve pregnancy in patients diagnosed with cervical or ovarian cancer

Blogger's Note: a slight bit more information

abstract: (cervical/ovarian) Gynaecological cancers in pregnancy : The Lancet

Blogger's Note: requires a subscription to view full paper $$$

open access: The Bangkok Statement on universal health coverage : The Lancet

"The theme of the Prince Mahidol Award Conference in Bangkok, Thailand on Jan 24—28, 2012, was Moving towards universal health coverage: health financing matters. At the close of the meeting, a 10-point declaration recognised universal health coverage (UHC) as fundamental to the right to health, and marked the commitment by more than 800 delegates to translate the rhetoric of UHC into better, more equitable health outcomes. Similar endorsements of UHC have been made before, including at the World Health Assembly in 2011. What makes the Bangkok Statement any more likely to hasten and widen the implementation of UHC?

One answer may be the power of the Prince Mahidol Award Conference and its sponsors to draw global health enthusiasts from a wide variety of disciplines and health systems. Delegates from 68 countries included donors and recipients of aid, managers and front-line health workers, ministers, economists, and consumers. From these many perspectives came the realisation that whether one seeks to provide access to health care for the 1 billion people who lack it, or to protect the 100 million people who end up in poverty every year as a result of medical costs, or to accelerate progress towards the Millennium Development Goals; UHC provides a common mechanism—and common cause. Simply put in a plenary by Peter Anyang' Nyong'o, Kenya's Minister for health services, “universal health coverage is fundamental to improving the lives of people.”.......

open access: Cancer treatment and care: a new and uneasy world : The Lancet

"......Thinking of the future, we sense oncological needs and expectations growing beyond what can be planned or provided for fairly. A drug like abiraterone, promising benefit in an area of evident clinical need, will have taken 20 years and substantial funds to develop. Early stage drug development is likely to have been undertaken by researchers with charitable or public funding, with the translational and clinical research by commercial entities leading, in abiraterone's case, to indelicate public haggling over how much 1 year of an average patient's life is reasonably worth....."

abstract: Prospective evaluation of molecular screening for Lynch syndrome in patients with endometrial cancer ≤ 70 years.

Blogger's Note: age >50 yrs will be at issue

Gynecol Oncol. 2012 Feb 1.

Abstract

OBJECTIVE:

Lynch syndrome (LS) is a hereditary syndrome that predisposes to multiple malignancies including endometrial cancer (EC). We aimed to evaluate a diagnostic strategy for LS based on routine analysis of microsatellite instability (MSI) and immunohistochemical (IHC) staining for mismatch repair (MMR) proteins in tumor tissue of all newly diagnosed EC patients ≤70years.

METHODS:

Consecutive EC patients ≤70years were included prospectively in eight Dutch centers. EC specimens were analyzed for MSI, IHC of four MMR proteins, MMR gene methylation status and BRAF-mutations. Tumors were classified as; 1) likely to be caused by LS, 2) sporadic MSI-H, or 3) microsatellite stable (MSS).

RESULTS:

Tumor specimens of 179 patients (median age 61years, IQR 57-66) were analyzed. In our study 92% of included patients were over 50 years of age. Eleven EC patients were found likely to have LS (6%; 95% CI 3-11%), including 1 patient suspected of an MLH1, 2 of an MSH2, 6 of an MSH6 and 2 of a PMS2 gene defect. Germline mutation analyses revealed 7 MMR gene germline mutations. Ten patients likely to have LS (92%) were older than 50years. In addition, 31 sporadic MSI-H tumors with MLH1 promoter hypermethylation (17%; 95% CI 13-24%) were identified.

CONCLUSIONS:

Molecular screening for LS in patients with EC diagnosed≤70years, leads to identification of a profile likely to have LS in 6% of cases. New screening guidelines for LS are needed, including recommendations for EC patients older than 50years of age.

video: Serving on a Clinical Practice Guideline Panel | US Cochrane Center