CMAJ: Who should hold the keys to your DNA?

Editor’s note: Third of a multipart series on genetic testing.
Part 1: Separating hype from reality in the era of the affordable genome (www.cmaj.ca/lookup/doi/10.1503/cmaj.109-4143).
Part 2: Popping the genetics bubble (www.cmaj.ca/lookup/doi/10.1503/cmaj.109-4142).
Next: Race and genetics in the doctor’s office



CMAJ: Who should hold the keys to your DNA?

"Opinion is divided over whether doctors or patients should be receiving the results of direct-to-consumer genetic tests........."

"“I think there is a need to think this through and to have some balance. On the one hand, we should respect consumers’ preferences and freedom to choose,” says Peter Neumann, director of the Center for the Evaluation of Value and Risk in Health at the Institute for Clinical Research and Health Policy Studies at Tufts Medical Center in Boston, Massachusetts and lead author on the paper. “We should also inform them about the risks and benefits.”
In some countries, governments have stepped in to ensure that doctors are the ones who must inform consumers about risks and benefits. Laws in France, Germany, Portugal and Switzerland stipulate that genetic tests only be administered by physicians. There are no regulations in Canada and few in the United States, though the US Food and Drug Administration has indicated that it will be stepping up efforts in the area...." 

Women of Teal: upcoming talk: speaker - Dee Sparacio (and blogger) Survivor to Survivor: Understanding Cancer Research

Monday, March 12, 2012

Survivor to Survivor: Understanding Cancer Research

I cordially invite you to attend my upcoming talk at the Cancer Support Community of Central New Jersey (3 Crossroads Drive, Bedminster, NJ).

Survivor to Survivor: Understanding Cancer Research

Thursday, March 15 • 6:30–7:30 pm Guest Speaker: Dee Sparacio, CSC Participant, Ovarian Cancer Survivor and Research Advocate Cure for Cancer Found–News at 11! What do the cancer research sound bites on the evening news mean for you? Learn how to read and interpret cancer research results from posters to journal articles. Find out which Web sites are reputable sources of cancer research information.

Please call 908-658-5400 to register.

Survey Reveals Pressures to Increase Volume of Colonoscopies Adversely Impacts How Gastroenterologists Perform the Screening and Could Potentially Affect Procedure Quality

Survey Reveals Pressures to Increase Volume of Colonoscopies Adversely Impacts How Gastroenterologists Perform the Screening and Could Potentially Affect Procedure Quality

OMICS Publishing Group | Full-text | Peutz-Jegher Syndrome in Gynecologic Pathology (PJS and ovarian cancer)

OMICS Publishing Group | Full-text | Peutz-Jegher Syndrome in Gynecologic Pathology

Seth's Blog: "It's not business, it's personal"

Seth's Blog:

"It's not business, it's personal"

It's too easy to blame the organization and the system and the bottom line for decisions that a person would never be willing to take responsibility for.
Whenever you can, work with people who take it personally.

abstract: Evaluation of ovarian cancer remission markers HE4, MMP7 and Mesothelin by comparison to the established marker CA125 (includes graphic/study of 23 patients)

 Highlights
(in study of 23 patients)

► Three new markers were compared to CA125 for lead time to ovarian cancer recurrence.
► HE4 elevates at recurrence when CA125 does not.
► Mesothelin has less marker potential, MMP7 shows promise and requires confirmation.
  
Evaluation of ovarian cancer remission markers HE4, MMP7 and Mesothelin by comparison to the established marker CA125: Publication year: 2012

Objective 
Evaluate and compare the effectiveness of CA125, HE4, Mesothelin and MMP7 marker levels to monitor ovarian cancer patients after surgery and chemotherapy. Evaluate the lead time of a rise of marker levels before recurrence.

Methods 
The study consists of 23 patients with advanced stage ovarian/fallopian tube cancer. Blood was drawn after front line surgery and chemotherapy treatment and at 3 month intervals thereafter. One patient had chemoresistant disease, two patients remained in remission and 20 patients had recurring disease and were used for marker evaluation.

Results
In five patients HE4 was the only marker to elevate before recurrence with a lead time of up to 4½ months including one patient who did not have a CA125 response at all. In a further two patients, HE4 increased before CA125 did. In four of these seven patients, HE4 levels were consistently at or above threshold during remission when both CA125 and imaging results were negative. MMP7 elevated before recurrence in one patient who was negative for the other markers. Mesothelin elevated in two patients who were also positive for CA125 and HE4.

Conclusions 
HE4 can predict ovarian cancer recurrence earlier than CA125 and it can be elevated in patients that do not express CA125 at sufficient levels to make a clinical decision. MMP7 and Mesothelin have lower potential as markers for ovarian cancer recurrence to complement CA125. A failure of HE4 levels to normalize at completion of standard therapy may indicate a poor prognosis.

Graphical Abstract

Highlights

► Three new markers were compared to CA125 for lead time to ovarian cancer recurrence.
► HE4 elevates at recurrence when CA125 does not.
► Mesothelin has less marker potential, MMP7 shows promise and requires confirmation.

repost from December 2011: A study of symptoms described by ovarian cancer survivors

A study of symptoms described by ovarian cancer survivors: Publication year: 2012

A phase I study with an expanded cohort to assess the feasibility of intravenous paclitaxel, intraperitoneal carboplatin and intraperitoneal paclitaxel in patients with untreated ovarian, fallopian tube or primary peritoneal carcinoma: A Gynecologic Oncology Group study

A phase I study with an expanded cohort to assess the feasibility of intravenous paclitaxel, intraperitoneal carboplatin and intraperitoneal paclitaxel in patients with untreated ovarian, fallopian tube or primary peritoneal carcinoma: A Gynecologic Oncology Group study


Objective 
To define the maximum tolerated dose (MTD) and assess the feasibility of intravenous (IV) paclitaxel, intraperitoneal (IP) carboplatin, and IP paclitaxel in women with newly diagnosed Stages II–IV ovarian, fallopian tube, or primary peritoneal carcinoma.

Methods 
Patients received escalating doses of paclitaxel IV and carboplatin IP on day 1 and paclitaxel IP 60mg/m² on day 8. A standard 3+3 design was used in the escalation phase. A two-stage group sequential design with 20 patients at the MTD was used in the feasibility phase. Patient-reported neurotoxicity was assessed pre and post treatment.

Results 
Patients were treated with paclitaxel 175mg/m² IV and carboplatin IP from AUC 5–7 on day 1 and paclitaxel 60mg/m² IP on day 8. The MTD was estimated at carboplatin AUC 6 IP and 25 patients enrolled at this dose level. Within the first 4cycles, seven (35%) of twenty evaluable patients had dose-limiting toxicities (DLTs) including grade 4 thrombocytopenia (1), grade 3 neutropenic fever (3), >2week delay due to ANC recovery (1), grade 3 LFT (1), and grade 3 infection (1). De-escalation to paclitaxel 135mg/m² IV was given to improve the safety. After six evaluable patients completed 4 cycles without a DLT, bevacizumab was added and six evaluable patients completed 4cycles with one DLT (grade 3 hyponatremia).

Conclusions 
Paclitaxel at 175mg/m² IV, carboplatin AUC 6 IP day 1 and paclitaxel 60mg/m² IP day 8 yield 18–56% patients with DLTs. The tolerability of the regimen in combination with bevacizumab was indicated in a small cohort.

abstract: Lymphatic ascites following pelvic and paraaortic lymphadenectomy procedures for gynecologic malignancies

 Blogger's Note: the abstract does not differentiate types of gyn cancers, journal is subscriber based ($$$)

Lymphatic ascites following pelvic and paraaortic lymphadenectomy procedures for gynecologic malignancies

Objective 
Lymphatic ascites is an unusual complication in patients with cancer. In the gynecologic oncology patient population, the most common etiology is operative lymph node dissection. The purpose of this study was to explore the incidence, presenting symptoms, methods of diagnosis and treatment modalities utilized for lymphatic ascites in patients undergoing lymph node dissection for gynecologic cancers.

Methods 
This observational study retrospectively reviewed the charts of patients who underwent lymphadenectomy as part of the surgical management for a gynecologic cancer. Patients that developed postoperative lymphatic ascites between January 2000 and December 2010 were included for analysis. Data extracted from the medical records included tumor pathology, number of harvested lymph nodes, postoperative course, method of diagnosis and treatment.

Results
From a total of 300 surgical staging procedures, 12 patients with lymphatic ascites were identified (4%). The most common reported symptom was leakage of clear fluid per vagina (7, 58%), followed by abdominal distension (4, 33%). The median interval from surgery to development of symptoms was 12.5 days (range 0–22days). 5 patients had complete resolution of symptoms with dietary modifications alone while 7 patients required paracentesis. The median time from surgery to resolution of symptoms was 44days (range 9–99).

Conclusion 
Lymphatic ascites is an under recognized and infrequently reported postoperative complication. Although it usually resolves spontaneously or with conservative management without sequelae, this condition can significantly prolong postoperative recovery and cause patient discomfort. To our knowledge this is the largest group of patients undergoing gynecologic surgical staging procedures to be reviewed for the occurrence of lymphatic ascites.

A phase II study of aflibercept in patients with advanced epithelial ovarian cancer and symptomatic malignant ascites

A phase II study of aflibercept in patients with advanced epithelial ovarian cancer and symptomatic malignant ascites

Objective 
The recombinant fusion protein, aflibercept binds and neutralizes vascular endothelial growth factor (VEGF) A, B and placental growth factor (PlGF). Aflibercept inhibits ascites formation and reduces tumor burden in an ovarian cancer model. This open-label, single-arm, multicenter phase II study assessed the efficacy and safety of aflibercept in patients with advanced chemo-resistant epithelial ovarian cancer and symptomatic malignant ascites.

Methods 
Patients who required ≥3 previous paracenteses at 1-4 paracenteses per month received intravenous aflibercept 4mg/kg every 2weeks. The primary endpoint was repeat paracentesis response rate (RPRR), with response defined as at least a two-fold increase in time to repeat paracentesis compared with the baseline interval.

Results 
Ten out of 16 enrolled patients achieved a response; the RPRR was 62.5% (95% CI 35.4%–84.8%). Aflibercept was considered effective based on a hypothesis that the RPRR was ≥60%. Median time to repeat paracentesis was 76.0 (95% CI 64.0–178.0) days, which was 4.5 times longer than the baseline interval (16.8days). Median progression-free survival was 59.5 (95% CI 41.0–83.0) days. Twelve patients experienced adverse events considered related to aflibercept treatment including hypertension (7 patients), headache, anorexia, and dysphonia (3 patients each). Two patients experienced Grade 3/4 treatment-related adverse events (Grade 3 hypertension and weight loss in one patient, Grade 3 intestinal perforation in one patient).

Conclusion 
Aflibercept 4mg/kg every 2weeks was effective at controlling malignant ascites, reducing the interval between repeat paracenteses. The safety profile was consistent with that reported for anti-VEGF agents.

Outcomes of surgical management of bowel obstruction in relapsed epithelial ovarian cancer (EOC)

Outcomes of surgical management of bowel obstruction in relapsed epithelial ovarian cancer (EOC):

Objective 
To describe the outcomes of surgical management of bowel obstruction in relapsed epithelial ovarian cancer (EOC) so as to define the criteria for patient selection for palliative surgery. Methods 90 women with relapsed EOC underwent palliative surgery for bowel obstruction between 1992 and 2008.

Conclusion 
Surgery for bowel obstruction in relapsed EOC is associated with a high morbidity and mortality rate especially in emergency cases when compared to other gynaecological oncological procedures. Palliation can be achieved in almost two thirds of cases, is equally likely in elective and emergency cases but is less likely in those with ascites.

abstract: Have racial disparities in ovarian cancer increased over time? An analysis of SEER data

Have racial disparities in ovarian cancer increased over time? An analysis of SEER data:

Objective 
Race has been postulated to be a prognostic factor in women with ovarian cancer. The reasons for racial disparities are multifactorial. Recent literature suggests that racial disparities in ovarian cancer survival emerged in the 1980s, when modern treatments such as aggressive surgical debulking and platinum-based chemotherapy first gained widespread use. We suspect that as improvements in treatment have evolved, the effects of access to treatment have amplified racial disparities in survival from ovarian cancer. Methods SEER 9 data were analyzed, including African American and white patients diagnosed with ovarian cancer from 1973 to 2007, with 2008 as the cutoff for follow-up. Using the Kaplan–Meier method, we evaluated racial differences in survival, to determine whether this difference has increased over time.

Results
There were 44,562 white and 3190 African American women available for analysis. Overall African Americans had 1.10 times the crude hazard (95% CI 1.06–1.15) of all-cause mortality compared to whites, with a widening trend over time (p<0.01). Adjusted for SEER registry, age, tumor stage, marital status and time of diagnosis, the hazard ratio (HR) for all-cause mortality comparing African Americans to whites was 1.31 (95% CI 1.26–1.37). When the receipt of surgery was added to the model, the HR for all-cause mortality remained higher for African American women at 1.27 (95% CI 1.21–1.34).

Conclusions 
African Americans diagnosed with ovarian cancer have worse survival than whites, and this disparity has increased over time. Measured differences in treatment, such as receipt of surgery, account for part of the disparity.

Disparities in hospice care among older women (over 65 yrs) dying with ovarian cancer

Disparities in hospice care among older women dying with ovarian cancer:

Background
Timely hospice referral is an essential component of quality end-of-life care, although a growing body of research suggests that for patients with various types of cancer, hospice referrals often occur very late in the course of care, and are marked by sociodemographic disparities. However, little is known about the ovarian cancer patient population specifically. We examined the extent and timing of hospice referrals in ovarian cancer patients over age 65, and the factors associated with these outcomes.

Methods
We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify 8211 women aged 66+ with ovarian cancer who were diagnosed between 2001 and 2005 and died by December 31, 2007. We excluded women who were not eligible for Medicare A continuously during the 6 months prior to death. Outcomes studied included overall hospice use in the last 6months of life and late hospice enrollment, defined as within 3 days of death. We examined variations in these two measures based on year of diagnosis and sociodemographic characteristics (age, race, marital status, rural residence, income, education) and type of Medicare received (fee-for-service vs. managed care).

Results 
Among 8211 women in the cohort who died from ovarian cancer, 39.7% never received hospice care (3257/8211). Overall hospice care increased over the period of observation, from 49.7% in 2001 to 74.9% in 2005, but the proportion of women receiving hospice care within 3days of death did not improve. Among those who received hospice care, 11.2% (556/4954) and 26.2% (1299/4954) received such care within 3 and 7 days of death, respectively. A higher proportion of black women (46.5% vs. 38.4% among whites), women in the lowest income group (42.8% vs. 37.0% in the highest income group), and those receiving fee-for-service Medicare (41.3% vs.33.5% for women in managed care) never received hospice care. In multivariable models, factors associated with lack of hospice care included age younger than 80 years (OR 1.27, 95% CI 1.15–1.40), non-white race (OR 1.44, 95% CI 1.26–1.65), low income (OR 1.17, 95% CI 1.04–1.32) and enrollment in fee-for-service Medicare compared with managed care (OR 1.39, 95% CI 1.24–1.56).

Conclusion 
More older women with ovarian cancer are receiving hospice care over time, however, a substantial proportion receive such care very near death, and sociodemographic disparities in hospice care exist. Our data also support the need to target lower-income and minority women in efforts to increase optimally timed hospice referrals in this population. Our finding that ovarian cancer patients enrolled in managed care plans were more likely to receive hospice care suggests the importance of health care system factors in the utilization of hospice services.

abstract: Combined treatment of L1CAM antibodies and cytostatic drugs improve the therapeutic response of pancreatic and ovarian carcinoma 10.1016/j.canlet.2011.12.035 : Cancer Letters | ScienceDirect.com

Combined treatment of L1CAM antibodies and cytostatic drugs improve the therapeutic response of pancreatic and ovarian carcinoma 10.1016/j.canlet.2011.12.035 : Cancer Letters | ScienceDirect.com

 Abstract

The adhesion molecule L1CAM (CD171) accounts for enhanced motility, invasiveness and chemoresistance of tumor cells and represents a novel marker for various tumor entities including pancreatic and ovarian carcinoma. Recently, we showed that L1CAM inhibition increases the apoptotic response of tumor cells towards cytostatic drugs pointing to the potential of L1CAM to serve as a chemosensitizer in anti-cancer therapy. Thus, the present study evaluated the therapeutic potential of combined treatment with L1CAM antibodies and chemotherapeutic drugs in pancreatic and ovarian carcinoma model systems in vivo.

open access: Adequacy of family history taking in ovarian cancer patients: a population-based study.

Blogger's Note: repost/open access

Adequacy of family history taking in ovarian cancer patients: a population-based study

Abstract:

The aim of this study was to evaluate the adequacy of family history taking in epithelial ovarian cancer (EOC) patients and to identify factors that determine adequacy. Furthermore, the validity of family history taking was assessed by comparison with self-administered questionnaires. Medical records of all 1,112 EOC patients registered by the nation-wide cancer registry and diagnosed in eleven Dutch hospitals between 1996 and 2006 were reviewed. Adequate family history taking was defined as a written notification of the presence or absence of relatives with breast or ovarian cancer. Factors that were correlated with family history taking were identified using univariable and multivariable logistic regression. 147 patients filled in a postal questionnaire. An adequate family history was taken in 41% of all cases. Younger age, an academic hospital and having undergone surgery and/or chemotherapy were associated with adequate family history taking. The comparison with self-administered questionnaires showed a disagreement in 64% mainly due to missing data in medical records. Documentation on family history is either absent or inadequate in the medical records in the majority of EOC patients. These data urge for better uptake of hereditary cancer risk assessment. Different strategies for this assessment like improved family history taking and genetic testing in EOC patients should be explored.

Why the Web Lacks Authoritative Reviews of Doctors - NYTimes.com

Why the Web Lacks Authoritative Reviews of Doctors - NYTimes.com

New Silicone Breast Implant Approved by FDA

New Silicone Breast Implant Approved by FDA

Recurrent germline mutations in BRCA... [Breast Cancer Res Treat. 2012] - PubMed - NCBI

Recurrent germline mutations in BRCA... [Breast Cancer Res Treat. 2012] - PubMed - NCBI
 Recurrent germline mutations in BRCA1 and BRCA2 genes in high risk families in Israel.

Abstract

The spectrum of germline mutations among Jewish non Ashkenazi high risk breast/ovarian cancer families includes a few predominant mutations in BRCA1 (185delAG and Tyr978X) and BRCA2 (8765delAG). A few additional recurring mutations [A1708E, 981delAT, C61G (BRCA1) R2336P, and IVS2 + 1G > A (BRCA2)] have been reported in Jewish non Ashkenazi families. The 4153delA*BRCA1 C61G*BRCA1 and the 4075delGT*BRCA2 has been reported to recur in Russian/Polish non Jews and Ashkenazim, respectively. The rate of these recurring mutations has not been reported in Israeli high risk families. Genotyping for these recurring mutations by restriction enzyme digest and sequencing method was applied to high risk, predominantly cancer affected, unrelated Israeli individuals of Ashkenazi (n = 827), non Ashkenazi (n = 2,777), non Jewish Caucasians (n = 193), and 395 of mixed ethnicity. Jewish participants included 827 Ashkenazi, 804 Balkans, 847 North Africans, 234 Yemenites, and 892 Asians (Iraq and Iran). Age at diagnosis of breast cancer (median ± SD) (n = 2,484) was 47.2 ± 9.6 for all women participants. Males (n = 236) were also included, of whom 24 had breast cancer and 35 had pancreatic cancer. Overall, 8/282 (2.8%) of the Balkan cases carried the BRCA1*A1708E mutation, 4/180 (2.2%) the R2336P mutation, and 0/270 the IVS2 + 1G > A BRCA2 mutations, respectively. Of North Africans, 7/264 (2.65%) carried the BRCA1*981delAT mutation. The BRCA1*C61G mutation was detected in 3/269 Ashkenazi, non Ashkenazi, and non Jewish Russians; the BRCA1*Tyr978X mutation was detected in 23/3220 individuals of non Ashkenazi origin, exclusively of Asian ethnicity (23/892, 2.6% of the Asians tested). The BRCA1*4153delA mutation was noted in 2/285 non Jewish Caucasians, and none of the Ashkenazim (n = 500) carried the BRCA2*4075delGT mutation. Jewish high risk families of North African, Asian, and Balkan descent should be screened for the 981delAT, Tyr978X, A1708E BRCA1, and the R2336P BRCA2 mutations, respectively.

abstract JCO: Opioid Prescription After Pain Assessment: A Population-Based Cohort of Elderly Patients With Cancer - Sunnybrooke Health Sciences Centre, Toronto, Canada

Opioid Prescription After Pain Assessment: A Population-Based Cohort of Elderly Patients With Cancer

 Abstract

Purpose The purpose of this study was to measure opioid prescription (OP) rates in elderly cancer outpatients around the time of assessment for pain and to evaluate factors associated with receiving OPs for those with severe pain. 

Patients and Methods The cross-sectional cohort includes all patients with cancer in Ontario older than age 65 years who completed a pain assessment as part of a provincial initiative of systematic symptom screening. Patients were assigned to mutually exclusive categories by pain score severity: 0, 1 to 3 (mild), 4 to 6 (moderate), and 7 to 10 (severe). We linked multiple provincial health databases to examine the proportion of patients with an OP within 7 days after or 30 days before the assessment date. We examined factors associated with OPs for patients with pain scores of 7 to 10. 

Results The proportion of patients with an OP increased as pain score severity increased: 10% of those with no pain, 24% of those with mild pain, 45% of those with moderate pain, and 67% of those with severe pain. More specifically, for those with severe pain, 41% filled an OP within 7 days of assessment for pain, and 26% had an OP from the 30 days before assessment for pain, leaving 33% without an OP. In multivariable analysis, factors associated with OPs are younger age, male sex, comorbid illness, cancer type, and assessment at home. 

Conclusion Despite a generous time window for capturing OPs, the proportion of patients without an OP seems high. Further knowledge translation is required to maximize the impact of the symptom screening initiative in Ontario and to optimize management of cancer-related pain.

open access: The use of telephone in genetic counseling versus in-person counseling: a randomized study on counselees’ outcome

"In total only 15% of the referred participants declined
participation in the questionnaire study, indicating a highly
motivated population. Non-participants were equally distributed
between telephone and in-person OGNC, speaking
in favor of an unbiased cohort."

"Given the results of our study, the option of a pre-counseling
telephone model could be an equal or even better
alternative to in-person counseling and could very well be a
standard mode in the future. The results show that a considerable
number of participants experienced difficulties
with the process of creating a pedigree and dissatisfaction
with information on recommended surveillance and prevention.
These items should be areas of improvement."

abstract: Time-varying incidence of cancer after the onset of type 2 diabetes: evidence of potential detection bias British Columbia, Canada

Time-varying incidence of cancer after the onset of type 2 diabetes: evidence of potential detection bias.:

Diabetologia. 2011 Sep;54(9):2263-71

Abstract

AIMS/HYPOTHESIS:
Despite the vast body of epidemiological literature on the risk of cancer in people with diabetes, few studies have examined the pattern of cancer risk during different time windows following diabetes onset. The objective of the study was to examine the risks of site-specific cancer in people with incident type 2 diabetes during different time windows following diabetes onset.

METHODS: 

This was a population-based retrospective cohort study. The study period was 1 April 1994 to 31 March 2006; censoring occurred at 31 March 2006, at death or on departure from British Columbia, Canada. Using linked health databases, we identified incident cohorts with and without diabetes, who were matched by age, sex and index year. Following a minimum 2-year cancer washout period, first site-specific cancers were identified prospectively in both cohorts.

RESULTS: 

Within 3 months following diabetes onset, participants with diabetes had significantly increased risks of colorectal, lung, liver, cervical, endometrial, ovarian, pancreatic and prostate cancers. After the initial 3-month period, the risks for colorectal (HR 1.15, 95% CI 1.05, 1.25), liver (HR 2.53, 95% CI 1.93, 3.31) and endometrial (HR 1.58, 95% CI 1.28, 1.94) cancers remained significantly elevated compared with those without diabetes.

The diabetes cohort remained at increased risk of pancreatic cancer in later years, but followed a different pattern: HR 3.71 at 3 months-1 year, 2.94 at 1-2 years, 1.78 at 2-3 years and 1.65 at 3-10 years (p value for all <0.01). After an initial period of elevated risk, men with type 2 diabetes subsequently had a decreased risk of prostate cancer (HR 0.82, 95% CI 0.76, 0.88).

CONCLUSIONS/INTERPRETATION: 

People with type 2 diabetes are at increased risk of select cancers; this risk is particularly elevated at the time of diabetes onset, which is likely to be due to increased ascertainment.

open access: Medscape - How Would Physicians Die?

How Would Physicians Die?


"How do doctors prefer to die? This question was addressed in a recent article on the Website zocalopublicsquare.org. The article suggests that physicians eschew extraordinary measures to extend life; instead they put a priority on reducing the pain and maximizing the quality of any limited time remaining. In a discussion on Medscape Physician Connect, an all-physician discussion group, doctors evaluated the accuracy of this portrait.
Overwhelmingly, the respondents agreed with sentiments expressed in the article. They sought to avoid the agony of a lingering final illness for themselves and for those they love. The results of an accompanying poll were unanimous. When completing the thought, "If I or my family were faced with a terminal illness with great potential for a terrible course and reasonable options have failed," all 27 respondents chose, "I'd want the focus to be on quality of life and comfort, no CPR." Not one expressed a preference for life-extending measures. Several physicians shared wrenching stories from personal experience...........cont'd

open access: CA-125: To Monitor or Not to Monitor?: Evidence Against Monitoring CA-125 For Ovarian Cancer Patients in Remission (Dr's Rustin, Karlan, Markman)

CA-125: To Monitor or Not to Monitor?: Evidence Against Monitoring CA-125

 For Ovarian Cancer Patients in Remission

Gordon Rustin, MD; Beth Y. Karlan, MD; Maurie Markman, MD

Authors and Disclosures

Posted: 03/08/2012

Editor's Note:
 
CA-125 is the most useful tumor marker in ovarian cancer. Since 1981, measurement of the serum level of the CA-125 antigen has become a standard component of routine management of women with advanced ovarian cancer.^[1,2] CA-125 concentrations are used to monitor response to chemotherapy, relapse, and disease progression in ovarian cancer patients. However, the question remains as to whether routine monitoring of CA-125 in women with advanced ovarian cancer in complete remission is advantageous. Recently, Drs. Gordon Rustin and Beth Karlan -- experts in the treatment of ovarian cancer -- participated in a Medscape Virtual Debate via email addressing the question, "Should patients with advanced ovarian cancer in complete remission undergo routine CA-125 monitoring?" Dr. Maurie Markman served as moderator. What follows is their conversation..........cont'd

open access: Expert Reviews - Current developments in ovarian cancer screening (March 2012)

Expert Reviews - Expert Review of Obstetrics & Gynecology - 7(2):131 - Full Text

ABSTRACT

Over 150 delegates from the UK, USA and Europe with a core interest in risk prediction and screening for ovarian cancer attended the International Conference on Ovarian Cancer Screening held on 29–30 November 2011 in London, UK. The scientific program was driven by two experts in the field – Usha Menon and Ian Jacobs – with assistance from the scientific committee, which included Steve Skates, Jatinderpal Kalsi, Anna Lokshin, Uzi Beller, Tim Mould and Ranjit Manchanda. Over the 2 days, key opinion leaders and researchers reported on the latest developments, and debated the future of risk prediction and screening for ovarian cancer.

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

The conference started with a welcome from Ian Jacobs (University of Manchester, Manchester, UK), followed by an overview of the current management of ovarian cancer (OC) by Tim Mould (University College Hospitals NHS Trust, London, UK). Stuart Campbell (Create Health Ltd, London, UK), a stalwart in the field of pelvic ultrasonography, chaired the first session on differential diagnosis in symptomatic patients. Robert Bast (University of Texas MD Anderson Cancer Center, TX, USA), who in the early 1980s discovered CA125, discussed recent biomarker panels and algorithms (Risk of Malignancy Index [RMI], Risk of Ovarian Malignancy Algorithm [ROMA] and OVA1) for OC diagnosis. His view was that the current challenge, especially in the USA, was implementation so that OC patients could be operated on by trained gynecological oncologists. Of the many OC markers, CA125 and HE4 provided the greatest discrimination between malignant and benign adnexal masses, with the latter particularly useful in premenopausal women..........cont'd

open access: Expert Reviews - Outlining novel scenarios for improved therapeutic cancer vaccines: the PANVAC paradigm (ovarian/breast)

Expert Reviews - Expert Review of Vaccines - 11(3):275 - Full Text
  
Outlining novel scenarios for improved therapeutic cancer vaccines: the PANVAC paradigm

Key issues

	• Heterologous prime—boost regimen with antigenically diverse recombinant poxviruses encoding for tumor-associated antigens and B7.1/ICAM-1/LFA3 cassette represents a most promising vaccination schedule inducing clinical and immunological responses.
	• PANVAC shows clinical efficacy in patients with metastatic breast and ovarian cancers.
	•  Patients with limited tumor burden and minimal prior chemotherapy had a benefit from PANVAC vaccination.
	• PANVAC was demonstrated to be immunologically active in some of the patients who developed clinical responses.
	• Overall survival, rather than progression-free survival, may be more relevant for addressing the effects of therapeutic cancer vaccines.
	• PANVAC, as also other cancer vaccines, elicits a dynamic process of immune responses, which may be exploited in subsequent therapies.
	• Vaccines used in the adjuvant setting (i.e., in patients with low tumor burden following conventional treatment) may be more efficacious than in patients with more advanced disease having increased tumor load.
	• Immunological end points as intermediate markers are needed for assessing clinical efficacy shortly after vaccination. Five-year view "The ultimate goal of therapeutic cancer vaccines should be to reduce the risk of recurrences in cancer patients with minimal residual disease or with no evidence of disease. In this case, therapeutic cancer vaccines, such as PANVAC, should be applied in the adjuvant setting after conventional therapies. However, therapeutic vaccination may also be applied in the metastatic setting, albeit in this case, it will likely need to be combined with chemotherapy. Considering the time of translation of vaccination-induced immune responses into clinical efficacy, median OS in the group of vaccinated patients may be affected at much later time points after treatment initiation compared to the group of patients receiving chemotherapy. Therefore, it becomes mandatory to plan clinical trials in such a way as to include start of assessments of clinical efficacy at later time points, which will also allow a better planning for interim analyses. OS as an end point for clinical vaccine trials poses a problem for making decisions about treatment efficacy after short-term assessment. Thus, there is a need for standardized immunological biomarkers as intermediate end points, which will be useful to determine clinical benefit shortly after immunotherapy. Such immunological end points will be essential to demonstrate the development of vaccine-induced immune responses and their clinical relevance. Novel immune-related response criteria are also essential for assessing clinical activity of cancer vaccines. Thus, developing optimized cancer vaccines and combining those with modalities aimed at improving their anticancer activity in well-designed clinical trials will open new avenues for the design of clinically effective cancer vaccine strategies. In this scenario, PANVAC may play a significant role in cancer immunotherapy for appropriately selected patients with cancer." Financial & competing interests disclosure   The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter discussed in the article. This includes employment, consultancies, stock ownership or options, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this article.

abstract: Clinical Outcome Prediction by MicroRNAs in Human Cancer: A Systematic Review

Clinical Outcome Prediction by MicroRNAs in Human Cancer: A Systematic Review

Background
MicroRNA (miR) expression may have prognostic value for many types of cancers. However, the miR literature comprises many small studies. We systematically reviewed and synthesized the evidence.

. ........The median hazard ratio for poor outcome in externally validated studies was 2.52 (IQR = 2.26–5.40). For all classifier miRs in studies that evaluated overall survival across diverse malignancies, the miRs most frequently associated with poor outcome after accounting for differences in miR assessment due to platform type were let-7 (decreased expression in patients with cancer) and miR 21 (increased expression).

Conclusions MiR classifiers show promising prognostic associations with major cancer outcomes and specific miRs are consistently identified across diverse studies and platforms. These types of classifiers require careful external validation in large groups of cancer patients that have adequate protection from bias.

pdf: Summaries for Patients - Surrogate Decision Makers’ Interpretation of Prognostic Information

Surrogate Decision Makers’ Interpretation of Prognostic Information

What are the implications of the study?

Inaccurate interpretations of doctors’ prognostications arise partly from optimistic biases rather than simply from misunderstandings. Helping surrogates attain realistic expectations about patients’ likely outcomes is more complex than just giving clear information.

Weighing the Chances at Life's End - NYTimes.com

Weighing the Chances at Life's End - NYTimes.com


"........But the grimmer the prognosis, the more inaccurate and more optimistic the surrogates’ responses became. Only 22 percent correctly interpreted a statement about what a “5 percent chance of surviving” meant, while 65 percent answered with greater optimism.
“They clearly grasped the meaning of these statements,” Dr. White said. “They were not misunderstanding the numbers. They weren’t misunderstanding the language.” If that had been the case, you’d expect them to have been inaccurate about good news, too.
Instead, relatives hearing doctors deliver dire prognoses just didn’t accept or believe them. They displayed, in medspeak, “a systematic optimism bias.”
Such bias has shown up many times before in the medical literature. Cancer patients enrolled in early phases of clinical trials, for instance,....."

Limited significance of family history for presence of BRCA1 gene mutation in Polish breast and ovarian cancer cases. (300T>G mutation)

Limited significance of family history for presence of BRCA1 gene mutation in Polish breast and ovarian cancer cases.:
Limited significance of family history for presence of BRCA1 gene mutation in Polish breast and ovarian cancer cases.
Fam Cancer. 2012 Mar 1;


Abstract
It is estimated that about 5-10% of ovarian and 2-5% of all breast cancer patients are carriers of a germline BRCA1 or BRCA2 gene mutation. Most families with detected BRCA1 or BRCA2 gene mutation are qualified for molecular testing on the basis of family history of breast or ovarian cancers. The purpose of our study was to establish the frequency of positive family history of cancer in a series of Polish consecutive breast and ovarian cancer patients in two groups, with and without the BRCA1 gene mutations. We analysed the prevalence of four of the most common BRCA1 mutations: 5382insC (c.5266dupC), 300T>G (p.181T>G), 185delAG (c.68_69delAG) and 3819del5 (c.3700_3704del5). The patient group consisted of 1,845 consecutive female breast and 363 ovarian cancer cases. 19 out of 37 (51%) of BRCA1-positive ovarian cancer patients and 21 out of 55 (39%) BRCA1-positive breast cancer had negative family history of breast and/or ovarian cancer among first- and second-degree relatives.

In ovarian cancer patients, negative family history was more frequent in those with 300T>G BRCA1 gene mutation than in 5382insC carriers. This finding indicates the necessity of searching for 300T>G mutation in families with a single diagnosis of ovarian cancer in family. The high frequency of mutations detected in breast cancer patients lacking obvious family history shows that breast cancer patients should be qualified for genetic testing on the basis of wide clinical and pathological criteria.

Impact of using multiple causes of death codes to compute site-specific, death certificate-based cancer mortality statistics in the United States

Impact of using multiple causes of death codes to compute site-specific, death certificate-based cancer mortality statistics in the United States: Publication year: 2012

Source:Cancer Epidemiology, Volume 36, Issue 1


Background: 
Cancer mortality statistics, an important indicator for monitoring cancer burden, are traditionally restricted to instances when cancer is determined to be the underlying cause of death (UCD) based on information recorded on standard certificates of death. This study's objective was to determine the impact of using multiple causes of death codes to compute site-specific cancer mortality statistics.

Methods:
The state cancer registries of California, Colorado and Idaho provided linked cancer registry and death certificate data for individuals who died between 2002 and 2004, had at least one cancer listed on their death certificate and were diagnosed with cancer between 1993 and 2004. These linked data were used to calculate the site-specific proportion of cancers not selected as the UCD (non-UCD) among all cancer-related deaths (any mention on the death certificate). In addition, the retrospective concordance between the death certificate and the population-based cancer registry, measured as confirmations rates, was calculated for deaths with cancer as the UCD, as a non-UCD, and for any mention.

Results: 
Overall, non-UCD deaths comprised 9.5 percent of total deaths; 11 of the 79 cancer sites had proportions greater than 3 standard deviations from 9.5 percent. The confirmation rates for UCD and for any mention did not differ significantly for any of the cancer sites.

Conclusion and impact:
The site-specific variation in proportions and rates suggests that for a few cancer sites, death rates might be computed for both UCD and any mention of the cancer site on the death certificate. Nevertheless, this study provides evidence that, in general, restricting to UCD deaths will not under report cancer mortality statistics.

(re: statistics) Comparison of methods for calculating relative survival in population-based studies

Comparison of methods for calculating relative survival in population-based studies: Publication year: 2012

Source:Cancer Epidemiology, Volume 36, Issue 1


Background: 

It is vital that unbiased estimates of relative survival are estimated and reported by cancer registries. A single figure of relative survival is often required to make reporting simpler. This can be obtained by pooling all ages or, more commonly, by using age-standardisation. The various methods for providing a single figure estimate of relative survival can give very different estimates.

Methods:

The problem is illustrated through an example using Finnish thyroid cancer data. The differences are further explored through a simulation study that investigates the effect of age on the estimates of relative survival.

Results: 

The example highlights that in practice the all-age estimates from the various methods can be substantially different (up to 6 percentage units at 15 years of follow-up). The simulation study confirms the finding that differing estimates for the all-age estimates of relative survival are obtained. Performing age-standardisation makes the methods more comparable and results in better estimation of the true net survival.

Conclusions: 

The all-age estimates of relative survival rarely give an appropriate estimate of net survival. We feel that modelling or stratifying by age when calculating relative survival is vitally important as the lack of homogeneity in the cohort of patients leads to potentially biased estimates. We feel that the methods using modelling provide a greater flexibility than life-table based approaches. The flexible parametric approach does not require an arbitrary splitting of the time-scale, which makes it more computationally efficient. It also has the advantage of easily being extended to incorporate time-dependent effects.

Postmenopausal hormone therapy and ductal carcinoma in situ: A population-based case–control study

Postmenopausal hormone therapy and ductal carcinoma in situ: A population-based case–control study: Publication year: 2012

Source:Cancer Epidemiology

Background and aim:

The relationship between hormone therapy (HT) and invasive breast cancer has been extensively investigated, but the relationship between HT and in situ breast cancer has received relatively little attention. We examined the relationship between HT and ductal carcinoma in situ (DCIS) among postmenopausal women who participated in a population-based case–control study in Connecticut, USA.

Methods: 

This analysis included 1179 post-menopausal women (603 controls and 576 cases), who comprised a subset of a population-based case–control study that included all incident cases of breast carcinoma in situ (BCIS) in Connecticut and frequency-matched controls by 5-year age intervals.

Results: 

We found no association between DCIS and ever use of any HT (adjusted odds ratio (OR)=0.85, 95% confidence interval (CI): 0.65–1.11); of estrogen alone (adjusted OR=0.93; 95% CI: 0.68–1.29) or of estrogen and progesterone (adjusted OR=0.75; 95% CI: 0.52–1.08). There was also no association between DCIS and current use of these hormones. In addition, estimated risk of DCIS did not increase with duration of use of these preparations. Conclusions: These results add to a small literature that remains inconclusive. To determine whether HT poses risk of in situ breast cancer, larger studies with greater power and precise control of important covariates (e.g., mammography screening) are needed, as are meta-analyses of available data.

Demanding dignity, and competence, in older people's care : The Lancet (several links of interest)

Demanding dignity, and competence, in older people's care : The Lancet

Other Articles of Interest

Articles Effect of dignity therapy on distress and end-of-life experience in terminally ill patients: a randomised controlled trial

Articles Dignity in the terminally ill: a cross-sectional, cohort study

Public Health Rediscovering human dignity

Comment Dignity and inequality

Commentary Death and dignity: dogma disputed

Cetuximab inhibits the growth of mucinous ovarian carcinoma tumor cells lacking... - Abstract - UK PubMed Central

Abstract

The purpose of this study was to explore the possibility of targeted molecular therapy with anti-epidermal growth factor receptor (anti-EGFR) antibody (cetuximab) for the treatment of mucinous ovarian carcinoma. ...............These results suggest the possibility of targeted molecular therapy with cetuximab for mucinous ovarian carcinoma cells lacking a KRAS gene mutation.

Activity and resistance of trastuzumab according to different clinical settings

Activity and resistance of trastuzumab according to different clinical settings: Publication year: 2012


Trastuzumab, a humanized monoclonal antibody directed against HER2, has shown efficacy in breast cancers; however many patients do not respond to this reagent. Here, we discuss the potential mechanisms of trastuzumab efficacy and resistance in different clinical settings as a step toward optimizing the appropriate application of this antibody. The three major antitumor mechanisms of trastuzumab, i.e., inhibition of proliferation, antibody-dependent cell cytotoxicity (ADCC) and inhibition of DNA repair, appear to be differentially operative in different clinical settings. ADCC appears to be the prevalent mechanism in trastuzumab neoadjuvant monotherapy, whereas in neoadjuvant, adjuvant or metastatic settings in which trastuzumab is combined with chemotherapy, the relative role of ADCC is probably small, considering the compromising effects of chemotherapy on the immune cells that mediate this mechanism. In neoadjuvant and adjuvant settings involving concomitant use of trastuzumab and chemotherapy, the primary mechanism at play is presumably inhibition of DNA repair by the antibody, while in sequential protocols, the antibody acts mostly by exerting cytostatic activity through inhibition of HER2-mediated tumor cell proliferation. According to the ability of the antibody to induce cytotoxic or cytostatic antitumor effects depending on the clinical setting, different criteria, i.e., RECIST for cytotoxic effect, OS, and DFS for cytostatic, must be considered in accurately estimating antibody efficacy. Moreover, since trastuzumab resistance likely depends directly on the mechanisms responsible for its antitumor activity, resistance mechanisms must also be considered with respect to the different clinical settings.

Importance of monitoring renal function in patients with cancer

Importance of monitoring renal function in patients with cancer: Publication year: 2012


Monitoring renal function in patients with solid tumors and hematologic malignancies is vital to the safe administration of therapeutic agents. Renal impairment is frequent in elderly patients (i.e., age⩾65) with cancer, despite normal serum creatinine levels in most patients. Because serum creatinine levels do not accurately reflect clearance rates, renal function should be estimated by calculation (either Cockcroft-Gault or abbreviated Modification of Diet in Renal Disease [aMDRD] equations) or by measuring creatinine clearance using a 24-h urine collection. Additionally, patients with cancer often have preexisting comorbidities or other risk factors that increase the probability of renal impairment before receiving potentially nephrotoxic therapies. Patient age, preexisting renal dysfunction, and chronic comorbidities (e.g., diabetes, kidney disease, hypertension, and cardiac insufficiency) all contribute to the risk of renal impairment. Furthermore, both cancer and its therapies may lead to renal impairment. A number of cancer therapy agents are nephrotoxic, including chemotherapy agents, molecular targeted agents, pain management agents, radiopharmaceuticals, contrast agents used in radiology, and antiresorptive agents, and contrast agents used in radiology are nephrotoxic as well. Undetected decreases in clearance rates by the kidneys can greatly increase exposure to treatment agents, possibly decreasing the safety of treatment and exacerbating renal impairment.
In conclusion, all cancer patients, not only those receiving potentially nephrotoxic agents, require renal monitoring.

Reliability, validity and feasibility of quality of life instruments for adult patients with cancer undergoing chemotherapy: result from a systematic review - 2012 - International Journal of Evidence-Based Healthcare

Abstract

Aim  The aim of this review was to analyse the literature critically and present the best available evidence related to quality of life (QoL) instruments that consists of all four subscales of physical, psychological, social and spiritual, which can be used in the clinical setting to assess adult patients with cancer on chemotherapy.

Inclusion criteria  This review included randomised control trials and observational studies without control group related to QoL instruments used for cancer chemotherapy. The types of participants for this review included all adults with cancer over the age of 18 years who have undergone chemotherapy. The QoL instruments for this review included instruments that consist of all subscales of physical, psychological, social and spiritual. In order to retrieve QoL instruments that were current and not outdated, this review included studies reported in the recent 10 years.

Results  A total of 3149 references was retrieved during the initial search. Only 13 articles with validation of the QoL instruments that contained all the four subscales of physical, psychological, social and spiritual were included in this review. Four QoL instruments were identified. These include the City of Hope QOL – Ovarian Cancer Tool (QOL-OVCA), QOL-Breast cancer version (QOL-BC) ........

Conclusion  In this review, there was one article on development of new QoL instrument, the New India QoL tool, which has comprehensive validity examinations – the least number of items that may be useful in the clinical setting but need further psychometric testing in different settings or languages. The QLI-CV instrument has had comprehensive intra- and inter-method validation on different languages, different cultural settings and various types of cancer. However, the instrument may not be feasible because the method to calculate the QoL score is not straightforward.

March 7th /text and/or podcast: PARP Inhibitors and the Challenges of Developing Ovarian Cancer Therapeutics - Cancer Network Dr's Ledermann/Birrer

Blogger's Note: podcast and/or text available, registration required (free)
                          ~~~~~~~~~~~~~~~~~~

PARP Inhibitors and the Challenges of Developing Ovarian Cancer Therapeutics - Cancer Network

Jonathan Ledermann, Cancer UK, London; Michael Birrer, Harvard Medical School, Dana-Farber Institute

AUDIO:
Right-click to download MP3

PODCAST 

PARP Inhibitors and the Challenges of Developing Ovarian Cancer Therapeutics

Interviewed by Anna Azvolinsky, PhD | March 7, 2012

---

Ovarian cancer is notoriously difficult to treat because it is usually diagnosed at an advanced stage, and because of the high variance in the types of mutations that are found in individual tumors. This creates hurdles for the development of efficacious treatments.
CancerNetwork presents an interview with two prominent ovarian cancer researchers from both sides of the Atlantic. Dr. Jonathan Ledermann is professor of medical oncology at the UCL Cancer Institute in London, England. He treats gynecological cancers and is heavily involved in ovarian cancer clinical trials. Dr. Michael Birrer is a professor of medicine at the Harvard Medical School and is part of the Dana-Farber/Harvard Cancer Center where he also treats gynecological cancers and leads an effort to molecularly characterize gynecological cancers.......

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

"CancerNetwork: Despite promising results at ASCO last year, with one of the PARP inhibitors, olaparib, showing positive progression-free survival (PFS) benefit, the phase II trial was stopped in mid December because this PFS benefit was not likely to translate to an overall survival benefit. I would like to get both of your perspectives on this and then what the future holds for other PARP inhibitors in development.



Dr. Ledermann: Mike Birrer will want to comment on this, but can I just correct you on a point of fact. The phase II trial was not stopped. In fact it is still going. There are still patients on treatment, and it has not been unblinded. What the company that manufactures olaparib, which is one of the PARP inhibitors, said in their press release was they were not going to continue development of olaparib in high-grade serous ovarian cancer because, as you said, the interim analysis of survival didn’t show the benefit they wanted to see in relation to the benefit in PFS that I reported at the ASCO conference. But the trial is still continuing and a final analysis will be done probably toward the end of this year."

Re-operation outcome in patients referred to a gynecologic oncology center with presumed ovarian cancer FIGO I-IIIA after sub-standard initial surgery

Re-operation outcome in patients referred to a gynecologic oncology center with presumed ovarian cancer FIGO I-IIIA after sub-standard initial surgery:

Publication year: 2012

Background 
Surgery is the mainstay of treatment for early ovarian cancer both as therapeutic and comprehensive staging. Only the latter allows appropriate tailoring of systemic treatment. However, the compliance with guidelines for comprehensive staging has been reported to be only moderate and, therefore, re-staging procedures are commonly indicated to avoid undertreatment. The purpose of our study was to evaluate re-operation in a tertiary gynecologic oncology unit after primary operation for presumably ovarian cancer FIGO I-IIIA in general gynecology departments.

Material and methods 
Forty consecutive patients after primary surgery in the outside institutions for presumed early ovarian cancer with assumed tumor spread limited to the pelvis (FIGO I-IIIA) admitted to our department between 1999 and 2007 were included. In 35 cases re-staging surgery in our unit was indicated. The intra- and post-operative results were compared with initial diagnosis and sites of undetected disease were evaluated. Reasons for re-staging and referral pattern were studied. Results 40 patients were enrolled of whom 53% came by self-referral. Only 18% were referred by the primary surgeon and the remaining patients were referred by their home gynecologist. Only 5 patients (13%) were classified as having had a comprehensive staging by surgical records and pathology reports and 35 patients underwent comprehensive re-staging laparotomy after which 20 patients (50%) experienced an upstaging including 13 patients with final diagnosis of FIGO stage IIIC. Most frequent sites of primarily undetected tumor were peritoneum (pelvic 34%, diaphragm 13%, paracolic 8%), lymph nodes (para aortic 32%, pelvic 11%), intestines 24%, and residual omental tissue 18%. The indication for post-operative chemotherapy was modified in 53% of patients.

Conclusion
Comprehensive staging of presumed early ovarian cancer has been described as major problem especially outside gynecologic oncology units. Re-staging results in our department confirmed this deficiency by showing a considerable proportion of upstaging associated with alterations of recommendations for systemic treatment. However, series like this may even underestimate the problem, because incomplete staging is unfortunately accompanied by non-systematic referral practices not reflecting staging quality.

open access: Progression-free Survival Decreases with Each Subsequent Therapy in Patients Presenting for Phase I Clinical Trials (study included various cancers including ovarian cancer) note: patient warning before reading

Blogger's Note: patient warning - this is not a 'good news' paper so caution advised

Table I 
Patient Diagnoses, Gender, Median Age at Diagnosis and Median Number of Therapies  (Blogger's Note: total patients = 142; ovarian cancer patients = 11)

Patient Characteristics

"We reviewed the patient records of 165 unique patients that were evaluated for participation in six phase I trials. Due to a lack of specific start/stop dates, 25 patients had at least one treatment censored for analysis; with one of these patients not having PFS that could be calculated for this study. Seventeen of these twenty-five patients were diagnosed as having less than stage IV disease, with the majority of censored treatments (radiation, surgery, or neoadjuvant or adjuvant chemotherapy) occurring in the non-advanced/metastatic setting. One hundred forty-four patients met criteria for receiving at least one prior non-investigational systemic therapy for advanced/metastatic cancer prior to coming for a phase I treatment evaluation. There were 77 men and 65 women; median age at cancer diagnosis was 55.3 years (range, 9.4 - 81.6 years). The most common types were: colorectal cancer (n=20 (13.9%)), other gastrointestinal cancer (n=17 (11.8%)), adenocarcinoma of the prostate (n=17 (11.8%)), non-small cell lung cancer (NSCLC) (n=13 (9.0%)), breast cancer (n=12 (8.3%)), ovarian cancer (n=11 (7.6%)), and adenocarcinoma of the pancreas (n=9 (6.3%)) (Table I). Patients had a median of three chemotherapy or hormonal treatments (mean, 3.32 treatments; range, 1 - 11 treatments).
Two of the 144 patients did not receive a second systemic therapy prior to evaluation at our center, so PFS could be calculated for the remaining 142 patients. The PFS from tx_n to tx_n+3 was significantly decreased (p = 0.001850) (Figure 1). Few advanced cancers have more than four lines of FDA-approved or consensus guidelines recommendations for systemic therapy, thus we examined the time to progression of the first five treatments (p = 2.938e-07) (Figure 2)."

open access journal (international) - Journal of Cancer

About this journal

Journal of Cancer is an open access, peer-reviewed journal with broad scope covering all areas of cancer research, especially novel concepts, new methods, new regimens, new therapeutic agents, and alternative approaches for early detection and intervention of cancer. The Journal is supported by an international editorial board consisting of a distinguished team of cancer researchers. Journal of Cancer aims at rapid publication of high quality results in cancer research while maintaining rigorous peer-review process.
Types of articles:

• Research paper
• Short research communication
• Review
• Letter to the editor

open access: Does the Loss of ARID1A (BAF-250a) Expression in Endometrial Clear Cell Carcinomas Have Any Clinicopathologic Significance? A Pilot Assessment (note comments re: clear cell ovarian)

"....Accordingly, their loss of function has been associated with malignant transformation. ARID1A (the expression of whose product, BAF250a, a key complex component, is lost when mutated) has recently been identified as a tumor suppressor gene that is mutated in 46-57% of ovarian clear cell carcinoma (CCC). The purposes of this study are to assess the frequency of loss of BAF250a expression in endometrial CCC and whether this loss has any discernable clinicopathologic implications....."

"....The fact that BAF250a expression is lost in only a small percentage of endometrial CCC may suggest that ARID1A mutations plays a significant role in only a small proportion of CCC, or that these mutations represent only a small component of the genesis of this specific tumor type. It may also bolster the argument that endometrial CCC represents a phenotype that arises via a multitude of different pathways (3,7), with no one pathway being notably dominant. However, it is unclear if those clear cell carcinomas whose pathogenesis does involve ARID1A mutations, represents a clinicopathologically distinct group with definable characteristics."

International Women's Day 2012

International Women's Day 2012

Behind the Headlines - Can endometriosis guide cancer tests? | GPonline.com

abstracts: 42nd annual SGO meeting - Gynecologic Oncology | Vol 125, Supplement 1, Pgs S1-S188, (March, 2012)

open access: Nature Reviews: Key Advances in Medicine - Ovarian Cancer/Markman page 15-16

Key Advances in Medicine (book)


Nature Reviews Clinical Oncology  (page 15)S11 ovarian cancer | Mutations and non-inferiority analyses show a way forward Maurie Markman      (page 15-16)






Highly clinically relevant ovarian cancer clinical research in 2011 focused on an increased understanding of the biology of the malignancy, limitations of strategies for early detection and screening, and the provocative reports of alternative primary and second-line management strategies.

"Although there were a number of very interesting
preliminary reports of therapeutic
advances in ovarian cancer in 2011 (for
example, bevacizumab in the first-line and
second-line management of the malignancy,
and olaparib  (Blogger's Note: links to Olaparib (parp inhibitor) - Cancer Research UK)  as maintenance therapy for
high-grade serous cancers), as of the writing
of this commentary these studies have not
appeared in the peer-reviewed oncology literature......."

Key advances
■■ There are currently no evidence-based
data supporting the clinical utility of any
ovarian cancer screening strategy in
non‑high-risk populations1
■■ Provocative data suggest there may be a
clinically meaningful difference between
the presence of a BRCA1 or a BRCA2
mutation in influencing outcome in ovarian
cancer6
■■ Under specific circumstances (for example,
neuropathy) it might be reasonable to
substitute pegylated liposomal doxorubicin
for paclitaxel in the front-line chemotherapy
management of ovarian cancer7

Markman, M. Nat. Rev. Clin. Oncol. 9, 69–70 (2012); published online 20 December 2011; doi:10.1038/nrclinonc.2011.200

                                   ~~~~~~~~~~~~~
"The articles included in Nature Reviews Key Advances in
Medicine were originally published in the February 2012
issues of the eight clinical Nature Reviews journals. The journals’
editors commissioned international experts to write a short
essay highlighting up to five key papers that made the biggest
contribution to their field in 2011."

The molecular basis of EPCAM expression loss in Lynch syndrome-associated tumors : Modern Pathology

The molecular basis of EPCAM expression loss in Lynch syndrome-associated tumors

Abstract

Germline deletions affecting the Epithelial cell adhesion molecule (EPCAM) gene lead to silencing of MSH2 and cause Lynch syndrome. We have recently reported that lack of EPCAM expression occurs in many, but not all tumors from Lynch syndrome patients with EPCAM germline deletions. The differences in EPCAM expression were not related to the localization of EPCAM germline deletions. We therefore hypothesized that the type of the second somatic hit, which leads to MSH2 inactivation during tumor development, determines EPCAM expression in the tumor cells. 

To test this hypothesis and to evaluate whether lack of EPCAM expression can already be detected in Lynch syndrome-associated adenomas, we analyzed four carcinomas and two adenomas from EPCAM germline deletion carriers for EPCAM protein expression and allelic deletion status of the EPCAM gene region by multiplex ligation-dependent probe amplification. 

In four out of six tumors we observed lack of EPCAM expression accompanied by biallelic deletions affecting the EPCAM gene. In contrast, monoallelic retention of the EPCAM gene was observed in the remaining two tumors with retained EPCAM protein expression. These results demonstrate that EPCAM expression in tumors from EPCAM deletion carriers depends on the localization of the second somatic hit that inactivates MSH2. 

Moreover, we report lack of EPCAM protein expression in a colorectal adenoma, suggesting that EPCAM immunohistochemistry may detect EPCAM germline deletions already at a precancerous stage.

Treatment for stromal tumors of the ovary - ACS

Treatment for stromal tumors of the ovary
Last Medical Review: 12/05/2011
Last Revised: 01/11/2012

YouTube video - Dealing With Recurrence - Dr John Comerci (NOCC) 43 minutes

"We know that the topic of recurrence in cancer patients can be an overwhelming and scary issue for any ovarian cancer survivor. In this video, Dr. John Comerci leads a discussion on recurrence and openly answered many questions from our survivor audience – hopefully yours will be one of them.
We appreciate Dr. Comerci’s contribution of his time and Magee Womnens Hospital of UPMC for providing the resources to make this lecture series possible."

abstract: Adjuvant Chemotherapy for Stage I Clear Cell Carcinoma of the Ovary: An Analysis of Fully Staged Patients

Adjuvant Chemotherapy for Stage I Clear Cell Carcinoma of the Ovary: An Analysis of Fully Staged Patients:

Objective: 

Although postoperative adjuvant chemotherapy is generally recommended for early-stage ovarian cancer, it remains unclear whether adjuvant chemotherapy is also effective for clear cell carcinoma (CCC).

Methods: 

Seventy-three patients with stage I CCC of the ovary who had undergone complete surgical staging formed the study population (stage IA, 20 patients; stage IC, 53 patients). Survival and multivariate analyses were retrospectively performed to determine the effectiveness of postoperative chemotherapy in these patients.

Results:

Of the total (73 patients), 30 patients received adjuvant chemotherapy (stage I C-positive), whereas 43 patients did not (stage I C-negative).

The 5-year progression-free survival (PFS) and 5-year overall survival (OS) rates for the stage I C-positive group were 80.1% and 87.4% compared with 73.9% and 81.7% for the stage I C-negative group.

The differences in survival between these groups were not significant (PFS: P = 0.610; OS: P = 0.557). Four of the patients with stage IA CCC underwent chemotherapy, whereas the remaining 16 patients received no additional therapy. No recurrence was observed in either group.

Of the patients with stage IC CCC, 26 patients underwent chemotherapy (stage IC C-positive) and 27 received no additional therapy (stage IC C-negative). There was no statistical difference in PFS and OS between the stage IC C-positive and stage IC C-negative groups.

Of the patients with stage IC without artificial rupture, the 5-year PFS rates of the C-positive and C-negative patients were 69.6% and 34.6%, respectively, but the 5-year OS rates were 75.0% and 70.0%, respectively (not significant).

Multivariate analyses confirmed that the presence or absence of adjuvant chemotherapy was not a prognostic indicator.

Conclusions:

The current study was performed only in fully staged patients, suggesting that postoperative adjuvant chemotherapy is not necessary for stage IA CCC patients.

For patients with stage IC CCC patients, adjuvant chemotherapy suppressed recurrence, but the effectiveness was insufficient in our limited study. Further studies are required to clarify this.

Editorial: Tumor Heterogeneity and Personalized Medicine — NEJM

Blogger's Note: this Editorial requires a subscription ($$$)

Editorial

Tumor Heterogeneity and Personalized Medicine

This article has no abstract; the first 100 words appear below.

"In the past 10 years, the number of tools available to treat cancer has increased, as has our understanding of what makes some cancers tick. The standard old-time cancer treatments were largely predicated on attacking DNA, an approach fueled by the belief that tumor cells divide more rapidly than normal cells. However, with the notable exception of Burkitt's lymphoma, only a small percentage of tumor cells in a patient are dividing at any given time. As we have learned more about DNA repair mechanisms and epigenetic alterations in cancers, DNA remains a viable target for new cancer therapies, but DNA . . ."

NEJM: Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing — Free Preview

Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing — NEJM

 Conclusions
Intratumor heterogeneity can lead to underestimation of the tumor genomics landscape portrayed from single tumor-biopsy samples and may present major challenges to personalized-medicine and biomarker development. Intratumor heterogeneity, associated with heterogeneous protein function, may foster tumor adaptation and therapeutic failure through *Darwinian selection.
       ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
* Synonym(s)

• Darwinian selection (natural selection)

Definition(s)

Natural evolutionary process that results in the survival of organisms best suited to changing living conditions through the perpetuation of desirable genetic qualities and the elimination of undesirable ones.

Setback reported in research into cancer treatment - (2nd media report)

BOSTON (AP) - "Scientists are reporting what could be very bad news for efforts to customize cancer treatment based on each person's genes.
They have discovered big differences from place to place in the same tumor as to which genes are active or mutated. They also found differences in the genetics of the main tumor and places where the cancer has spread.
This means that the single biopsies that doctors rely on to choose drugs are probably not giving a true view of the cancer's biology. It also means that treating cancer won't be as simple as many had hoped."

"By analyzing tumors in unprecedented detail, "we're finding that the deeper you go, the more you find," said one study leader, Dr. Charles Swanton of the Cancer Research UK London Research Institute in England. "It's like going from a black-and-white television with four pixels to a color television with thousands of pixels."
Yet the result is a fuzzier picture of how to treat the disease.
The study is reported in Thursday's New England Journal of Medicine.
It is a reality check for "overoptimism" in the field devoted to conquering cancer with new gene-targeting drugs, Dr. Dan Longo, a deputy editor at the journal, wrote in an editorial."

Cancer gene mutation more complex than previously thought: study | Reuters

"LONDON | Thu Mar 8, 2012 3:31am IST
 

(Reuters) - Taking a sample or biopsy from just one part of a tumor might not give a full picture of its genetic diversity and may explain why doctors, despite using genetically targeted drugs, are often unable to save patients whose cancer has spread, scientists said.
A study by British researchers found there are more genetic differences than similarities between biopsies taken from separate areas of the same tumor, and yet further gene differences in samples taken from secondary tumors......

DPX-Survivac vaccine - Biotech company raises $2.8 million for R&D | The Chronicle Herald

"Halifax biotechnology company Immunovaccine Inc. has raised $2.8 million in equity funding that will help the company push forward with clinical trials of its anti-cancer vaccine.

“The proceeds will be used to fund research and development and for our other corporate activities,” Immunovaccine chief financial officer Kimberley Stevens said Wednesday.

Foremost among those R&D efforts are the Phase 1 clinical trails on patients with advanced-stage ovarian cancer for DPX-Survivac, Immunovaccine’s therapeutic cancer vaccine. In January, the first patient was vaccinated in the trials, which have been simultaneously approved in Canada and the United States.

The company, through the non-brokered private placement, issued 9,294,005 common shares at 30 cents each to raise the funds.
Under Phase 1 trials, patients in Canada and the United States will be treated with DPX-Survivac after completing debulking surgery — the removal of part of a tumour — and chemotherapy treatments.
If the vaccine is found to be safe for humans, testing will proceed to Phase 2.

Typically, if a vaccine passes Phase 2, the company either licenses it or partners with a big drug company before beginning definitive tests that regulatory agencies use to decide whether to approve a product.
Stevens said the $2.8 million in fresh equity will be enough for Immunovaccine to operate until the first quarter of 2013 before it needs to raise new funds.

abstract: A systematic review of large-scale surveys of cancer survivors conducted in North America, 2000-2011.

A systematic review of large-scale surveys of cancer survivors conducted in North America, 2000-2011.

INTRODUCTION:

Many large surveys collect data on cancer survivors, but few encompass the full spectrum of domains relevant to survivorship ranging from cancer care to quality of life to late- and long-term effects of cancer and its treatment. Here, we review large data sources in North America collecting cancer survivor-reported health information, and catalogue the domains of cancer survivorship each includes.

METHODS:

We identified surveys of cancer survivors through a comprehensive web search of federal government agencies, non-profit organizations, and related societies that support health care research or provide health care services, as well as a systematic review of literature indexed on PubMed from 2000-2011.

RESULTS:

A total of 57 surveys were identified, 26 nationally representative surveys and 31 regional, state, or provincial surveys. Thirty-four surveys specifically targeted cancer survivors, and an additional two surveys had supplements or modules targeted at cancer survivors. Among the nationally representative surveys, general medical characteristics and medical conditions were the most frequently reported cancer survivorship domains, and information on cancer-related costs was least frequently reported.

DISCUSSION/CONCLUSION:

Our review demonstrates that a large and growing number of surveys across the U.S. and Canada are collecting data on cancer survivors. These surveys differ in design, geographic region, primary population of interest, cancer site, and research areas of interest. They address a wide range of survivorship issues. Future cancer survivorship research should concentrate on understudied areas in order to better understand the challenges faced by this growing population.