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Saturday, August 01, 2015

A phase II study of ramucirumab (IMC-1121B) in the treatment of persistent or recurrent epithelial ovarian, FT or PP carcinoma

Gynecol Oncol. 2014 Sep;134(3):478-85. doi: 10.1016/j.ygyno.2014.06.029. Epub 2014 Jul 10.

A phase II study of ramucirumab (IMC-1121B) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma.


Vascular endothelial growth factor (VEGF) receptor-mediated signaling contributes to ovarian cancer pathogenesis. Elevated VEGF expression is associated with poor clinical outcomes. We investigated ramucirumab, a fully human anti-VEGFR-2 antibody, in patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. Primary endpoints were progression-free survival at 6 months (PFS-6) and confirmed objective response rate (ORR).


Women who received ≥ 1 platinum-based chemotherapeutic regimen and had a platinum-free interval of <12 months with measurable disease were eligible. Patients received 8 mg/kg ramucirumab intravenously every 2 weeks.


Sixty patients were treated; one patient remained on study as of September 2013. The median age was 62 years (range: 27-80), and median number of prior regimens was 3. Forty-five (75%) patients had platinum refractory/resistant disease. Thirty-nine patients (65.0%) had serous tumors. PFS-6 was 25.0% (n=15/60, 95% CI: 14.7-37.9%). Best overall response was: partial response 5.0% (n=3/60), stable disease 56.7% (n=34/60), and progressive disease 33.3% (n=20/60). The most common treatment-emergent adverse events possibly related to study drug were headache (65.0%; 10.0% Grade ≥ 3), fatigue (56.7%; 3.3% Grade ≥ 3), diarrhea (28.3%; 1.7% Grade ≥ 3), hypertension (25.0%; 3.3% Grade ≥ 3), and nausea (20.0%; no Grade ≥ 3). Two patients experienced intestinal perforations (3.3% Grade ≥ 3). Pharmacodynamic analyses revealed changes in several circulating VEGF proteins following initial ramucirumab infusion, including increased VEGF-A, PlGF and decreased sVEGFR-2.


Although antitumor activity was observed, the predetermined efficacy endpoints were not met.

Note: Risk of gastrointestinal perforation in cancer patients receiving ramucirumab: a meta-analysis of randomized controlled trials

Risk of gastrointestinal perforation in cancer patients receiving ramucirumab: a meta-analysis of RCTs

Although existing evidence from clinical trials has demonstrated manifestation of gastrointestinal perforation with the use of ramucirumab, overall risks have yet to be reported. Therefore, we performed a meta-analysis of published randomized controlled trials (RCTs) to get a better understanding of the overall incidence and risk of gastrointestinal perforation associated with ramucirumab.

The PubMed and Web of Science databases as well as abstracts presented at American Society of Clinical Oncology conferences were searched to identify relevant studies published up to 01 May 2015. Eligible studies included randomized trials of ramucirumab either alone or in combination with another agent compared with the control arm without ramucirumab and that reported gastrointestinal perforation event. Overall incidence, relative risk (RR) and 95% confidence intervals (CI) were computed using fixed- or random-effects models depending on the heterogeneity of the included studies.

A total of 4579 patients with a variety of solid malignancies from six RCTs were included in our meta-analysis. The incidence of gastrointestinal perforation related to ramucirumab was 1.5% (95% CI 1.1–2.1%) with a mortality of 29.8% (95% CI 14.9–50.7%). The RR of gastrointestinal perforation associated with ramucirumab was 2.56 (95% CI 1.29–5.09; P  =  0.007).

Treatment with the ramucirumab is associated with a significant increase in risk of gastrointestinal perforation in cancer patients.


Ramucirumab in Ovarian Cancer - clinical trial


This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
First received: July 21, 2008
Last updated: January 12, 2015
Last verified: January 2015

BRCA Mutations, DNA Repair Deficiency and Ovarian Aging

open access

.....  We find that BRCA mutations negatively affect ovarian reserve based on convincing evidence from in vitro and in vivo evidence and prospective studies. Because decline in the function of the intact gene occurs at an earlier age, women with BRCA1 mutations exhibit accelerated ovarian aging unlike those with BRCA2 mutations. However, because of the still robust function of the intact allele in younger women and due to masking of most severe cases by prophylactic oophorectomy
or cancer, it is less likely to see an effect of BRCA mutations on fertility until later in
reproductive age......

Cellular and molecular processes in ovarian cancer metastasis


 Ovarian cancer is the most lethal gynecological malignancy. It is usually diagnosed at a late stage, with a 5-year survival rate of less than 30%. The majority of ovarian cancer cases are diagnosed after tumors have widely spread within the peritoneal cavity, limiting the effectiveness of debulking surgery and chemotherapy. Owing to a substantially lower survival rate at late stages of disease than at earlier stages, the major cause of ovarian cancer deaths is believed to be therapy-resistant metastasis3. Although metastasis plays a crucial role in promoting ovarian tumor progression and decreasing patient survival rates, the underlying mechanisms of ovarian cancer spread have yet to be thoroughly explored. For many years, researchers have believed that ovarian cancer metastasizes via a passive mechanism by which ovarian cancer cells are shed from the primary tumor and carried by the physiological movement of peritoneal fluid to the peritoneum and omentum. However, the recent discovery of hematogenous metastasis of ovarian cancer to the omentum via circulating tumor cells instigated rethinking of the mode of ovarian cancer metastasis and importance of the "seed and soil" hypothesis for ovarian cancer metastasis. In this review, we discuss the possible mechanisms by which ovarian cancer cells metastasize from the primary tumor to the omentum, the cross-talk signaling events between ovarian cancer cells and various stromal cells that play crucial roles in ovarian cancer metastasis, and the possible clinical implications of these findings in the management of this deadly, highly metastatic disease.

Trends & Analysis of Cancer Incidence for Common Male & Female Cancers (Pakistan)

 Trends and Analysis of Cancer Incidence for Common Male and Female Cancers in the Population of Punjab Province of Pakistan during 1984 to 2014.


The Pakistan Atomic Energy Commission Cancer Registry (PAECCR) program has made availability of a common cancer incidence database possible in Pakistan. The cancer incidence data from nuclear medicine and oncology institutes were gathered and presented.


The cancer incidence data for the last 30 years (1984-2014) are included to describe a data set of male and female patients. The data analysis concerning occurrence, trends of common cancers in male and female patients, stage-wise distribution, and mortality/follow-up cases is also incorporated for the last 10 years (2004-2014).


The total population of provincial capital Lahore is 9,800,000. The total number of cancer cases was 80,390 (males 32,156, females 48,134). The crude incidence rates in PAECCR areas were 580.8/105 during 2010 to 885.4/105 in 2014 (males 354.1/105, females 530.1/105). The cancer incidence rates for head and neck (15.70%), brain tumors (10.5%), and non-Hodgkin lymphoma (NHL, 9.53%) were found to be the highest in male patients, whereas breast cancer (46.7%), ovary tumors (6.80%),

Effect of Previous Chemotherapy on the Quality of Cryopreserved Human Ovarian Tissue In Vitro.



Cryopreservation of ovarian tissue has been widely accepted as an option for fertility preservation among cancer patients. Some patients are exposed to chemotherapy prior to ovarian tissue cryopreservation. Consequently, assessment of the developmental capacity of human ovarian tissue after chemotherapy is of primary importance.


In order to study the impact of previous chemotherapy on in vitro development and viability of ovarian follicles, quality control samples from 34 female cancer patients at median age of 15 years (range 1‒35),

Targeting c-MYC in platinum-resistant ovarian cancer


 These findings identify c-MYC as a potential therapeutic target for ovarian cancers expressing high levels of this oncoprotein.

Friday, July 31, 2015

Hereditary Ovarian Cancer: Not Only BRCA 1 and 2 Genes

2015 open access


More than one-fifth of ovarian tumors have hereditary susceptibility and, in about 65–85% of these cases, the genetic abnormality is a germline mutation in BRCA genes. Nevertheless, several other suppressor genes and oncogenes have been associated with hereditary ovarian cancers, including the mismatch repair (MMR) genes in Lynch syndrome, the tumor suppressor gene, TP53, in the Li-Fraumeni syndrome, and several other genes involved in the double-strand breaks repair system, such as CHEK2, RAD51, BRIP1, and PALB2. The study of genetic discriminators and deregulated pathways involved in hereditary ovarian syndromes is relevant for the future development of molecular diagnostic strategies and targeted therapeutic approaches. The recent development and implementation of next-generation sequencing technologies have provided the opportunity to simultaneously analyze multiple cancer susceptibility genes, reduce the delay and costs, and optimize the molecular diagnosis of hereditary tumors. Particularly, the identification of mutations in ovarian cancer susceptibility genes in healthy women may result in a more personalized cancer risk management with tailored clinical and radiological surveillance, chemopreventive approaches, and/or prophylactic surgeries. On the other hand, for ovarian cancer patients, the identification of mutations may provide potential targets for biologic agents and guide treatment decision-making.

1. Introduction
2. Clinical, Histopathological, and Molecular Features of Ovarian Cancer
3. Mismatch Repair Genes and Lynch Syndrome
4. TP53 and Li-Fraumeni Syndrome
5. Genes Involved in Double-Strand Breaks Repair
6. Next-Generation Sequencing with Multigene Panels
7. Conclusions
.....The centralization of genetic testing enables the improvement of access and quality of testing and allows for the creation of a more comprehensive database for research, guiding evidence-based management recommendations [89–91].

Call for Abstracts & Surgical Films: SGO 2015



The 2016 SGO International Program will emphasize global gynecologic cancer epidemiology.  Our goals are to identify geographic variations in the worldwide gynecologic cancer incidence with a particular emphasis on the burden of gynecologic cancers in low- and middle-income countries, the challenges of public health reporting, and examples of successful models for the development and implementation of reliable and accurate cancer registries.  
The key concepts for presentation consideration include:
  • Epidemiology
  • Regional demographics and trends
  • Treatment in developing countries
  • Challenges in public health and data ascertainment
  • Screening challenges
  • Breast cancer

For younger women | Target Ovarian Cancer

2015 Ovarian Cancer National Conference (with images, tweets) · OCNA · Storify



Thursday, July 30, 2015

Acelarin cancer drug impact hope 'remarkable' - BBC News

media report from May 30th

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


 Impact of Age and Primary Disease Site on Outcome in Women With Low-Grade Serous Carcinoma of the Ovary or Peritoneum: Results of a Large Single-Institution Registry of a Rare Tumor 
Purpose Low-grade serous carcinoma of the ovary (LGSOC) or peritoneum (LGSPC) is a rare subtype of ovarian or peritoneal cancer characterized by young age at diagnosis and relative resistance to chemotherapy. The purpose of this study is to report our updated experience with women diagnosed with LGSOC or LGSPC to assess the validity of our original observations.

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

Epidemiology in ovarian carcinoma: Lessons from autopsy


Autopsy data challenges epidemiologic knowledge regarding incidence and prevalence of ovarian carcinoma.
Previous epidemiological data overestimate incidence because up to 10% of carcinomas in the ovary were metastases from other primary sites.
In 16% of autopsies, ovarian carcinoma in its final stage was first diagnosed by autopsy.


We challenge epidemiologic knowledge regarding ovarian carcinoma (OC) by bridging the gap between clinical and autopsy data.


Autopsy reports, histological slides and clinical files from 660 patients in whom OC was diagnosed from 1975-2005 were studied (autopsy cohort, n = 233; Clinical Cancer Registry from the local gyneco-oncologic center, n = 427).


Out of the autopsy cohort, we identified four distinct subgroups of patients: 1) OC was diagnosed before autopsy, n = 156 (67.0%). 2) OC was an incidental finding, n = 16 (6.8%). 3) The ovarian tumors were not primary OC but rather metastases from other primary tumors; this revised diagnosis was first made by using current histopathological knowledge/techniques, n = 24 (10.3%). 4) Death was directly due to OC in its final stage and OC was first diagnosed by autopsy, n = 37 (15.9%); when these cases were added to the Clinical Cancer Registry to an adjusted OC incidence model, the autopsy cases comprised 8.8% of the adjusted cohort and almost doubled the percentage of oldest patients (≥ 80 years at diagnosis) from 4.9% to 9.3% (p = 0.013).


Epidemiological data from the 1970s-1990s may overestimate true incidence because up to 10% of carcinomas in the ovary were not properly classified. Patients who were first diagnosed with OC by autopsy comprise a distinct subgroup. These are patients who have not been seen by specialized oncologists and thus play no role in their perception of the disease. Nevertheless, these cases have impact on prevalence and incidence data of OC and in an era of reduced autopsy rates will probably be overlooked.

Gynecologic Oncology INDEX (August 2015)

Gynecologic Oncology | Vol 138, Iss 2, Pgs 221-494, (August 2015)

Improvement in quality of life after robotic surgery results in patient satisfaction

  • Women were satisfied with their decision to undergo robotic surgery.
  • General health, symptom burden, and sexual function returned to baseline quickly after robotic surgery.


There are well-described benefits to minimally invasive surgery including decreased blood loss, shorter hospital-stay, and faster recovery. The role of robotic surgery in gynecologic oncology has become increasingly prominent; however limited data are available on quality of life (QOL) after robotic surgery.


In this prospective, IRB-approved study, women scheduled for robotic surgery for a gynecologic indication between May 2008 and February 2012 completed validated QOL measures at baseline, 6 weeks (6 wk), and 4 months postoperative (4 mo).

Outcome of neoadjuvant chemotherapy in BRCA1/2 mutation positive women with advanced stage Müllerian cancer



  • Patients with germline BRCA mutations had improved outcomes with NAC compared to patients with unknown BRCA status.
  • The outcomes of NAC in BRCA mutation positive patients were more favorable than the outcomes reported in the literature.
  • This is the first study evaluating the outcome of NAC in BRCA mutation positive patients with advanced-stage mullerian cancer.


To investigate whether patients with germline BRCA1/2 mutations who received neoadjuvant chemotherapy (NAC) for advanced stage Mullerian cancer (MC) have an improved outcome compared to patients who did not undergo genetic testing.


Three hundred and two patients who received NAC for stage III-IV MC were identified from a multi-institutional study involving Cleveland Clinic and Brigham and Women’s Hospital for 2000–2014 and 2010–2014 respectively. Patients were divided into 3 cohorts: patients with germline BRCA 1/2 mutations (BRCA_mut+; N = 30), patients with no genetic testing (BRCA_unk; N = 166) and patients with negative genetic testing (BRCA mut-, N = 106).


There were no differences in the clinical characteristics and rates of complete cytoreduction and bowel resection between the three groups. BRCA_mut + had longer PFS compared to BRCA_unk and BRCA_mut- (19.1 vs. 15.1 vs. 15.7 months respectively. However, this difference was not statistically significant (p = 0.48). Patients with BRCA 2 mutation had non-significant trend toward longer PFS compared to patients with unknown BRCA or BRCA 1 mutation (20.2 vs. 15.1 vs. 14.8 months respectively, p = 0.58). BRCA-mut + and BRCA_mut-had longer overall survivals (OS) compared to BRCA_unk patients (50.5 vs. 54.1 vs. 36.5 months respectively, p = 0.009). In multivariable analyses, controlling for age, stage and complete cytoreduction, BRCA_mut_unk was associated with worse PFS (HR 1.44, 95% CI 1.01-2.05, p = 0.045) and OS (HR 2.67, 95% CI 1.33-5.36, p = 0.006).


Patients with germline BRCA mutations had improved outcomes with NAC compared to patients with unknown BRCA status. These outcomes were more favorable compared to the outcome of NAC in prior studies.

Ascites predicts treatment benefit of bevacizumab in front-line therapy of advanced epithelial ovarian, fallopian tube and peritoneal cancers: An NRG Oncology/GOG study


  • We analyzed data from GOG 0218 to determine if ascites predicts response to bevacizumab.
  • Ascites was shown to be a negative prognostic factor in epithelial ovarian cancers.
  • Ascites is a significant clinical factor that may predict response to bevacizumab.


Predictive factors for efficacy of bevacizumab in advanced ovarian cancer have remained elusive. We investigated ascites both as a prognostic factor and as a predictor of efficacy for bevacizumab.


Using data from GOG 0218, patients receiving cytotoxic therapy plus concurrent and maintenance bevacizumab were compared to those receiving cytotoxic therapy plus placebo. The presence of ascites was determined prospectively. Chi-square and Wilcoxon–Mann–Whitney tests compared baseline variables between subgroups. Survival was estimated by Kaplan–Meier method, and Cox proportional hazard models were used to evaluate independent prognostic factors and estimate their covariate-adjusted effects on survival.


Treatment arms were balanced with respect to ascites and other prognostic factors. Overall, 886 (80%) women had ascites, 221 (20%) did not.

Wednesday, July 29, 2015

Postoperative hormone replacement therapy for epithelial ovarian cancer patients: a systematic review and meta-analysis - Gynecologic Oncology



  • This is the first meta-analysis on the effect of HRT on prognosis and recurrence of EOC survivors.
  • Postoperative HRT use is not associated with poorer clinical outcomes of EOC patients.


. Hormone replacement therapy (HRT) has been proven highly effective for menopausal symptoms caused by radical surgery. However, the impact of postoperative HRT on the clinical outcomes of patients previously treated for epithelial ovarian cancer (EOC) remains unclear.


. To determine whether postoperative HRT use has any positive or negative impacts on prognosis and recurrence among EOC survivors.


. Studies that provided an assessment of postoperative HRT use and prognosis or recurrence in EOC patients were included for analysis. Two reviewers independently evaluated the eligibility of identified studies and abstracted the data. A fixed effects model was used to pool study-specific estimates of hazard ratios (HRs) or relative risks (RRs) with 95% confidence intervals (CIs).


. Two randomized controlled trials (RCTs) and four cohort studies included 419 EOC survivors who used HRT and 1,029 non-users. The aggregated HR of overall survival (OS) suggested that HRT use after surgery for EOC had a favorable impact on OS (HR = 0.69, 95% CI: 0.61–0.79), but when these studies were categorized into cohort study and RCT subgroups, not all of them demonstrated positive results (HR = 0.63, 95% CI: 0.49–0.81 and HR = 1.03, 95% CI: 0.58–1.83, respectively). The meta-analysis of EOC recurrence of three available studies demonstrated that postoperative HRT use was not associated with an increased risk of recurrence in EOC survivors (RR = 0.83, 95% CI: 0.64–1.07). This pattern also emerged in the subgroup analysis for the stage and type of HRT.


. In EOC patients, postoperative HRT does not have a negative effect on overall survival and tumor recurrence. However, well-designed and large-scale RCTs are needed to verify this relationship in the future.

Setting the bar: compliance with ovarian cancer quality indicators at a NCI-designated Comprehensive Cancer Center



  • Appropriate quality indicator thresholds must take into account our complex patients
  • Complete surgical staging and timely administration of chemotherapy warrant attention
  • Existing perioperative quality measures demonstrate excellent compliance


Ovarian cancer quality measures are being developed to improve health care delivery and outcomes. Our objective is to evaluate compliance with 8 quality indicators proposed by the Society of Gynecologic Oncology.


Review of 123 ovarian cancer patients who underwent primary surgical staging/cytoreduction and chemotherapy from 2010–2012 was undertaken. Medical records were reviewed, and descriptive statistics were performed to determine compliance.


A timely operative report documenting residual disease was dictated for 121/123 (98.4%) patients. Complete surgical staging was performed in 33/55 (60.0%) stage I-IIIB patients, with lymphadenectomy most frequently omitted. For optimally debulked stage III patients, 52/56 (92.9%) were offered intraperitoneal chemotherapy. Ultimately, 29/56 (51.8%) received this route and 19/56 (33.9%) within 42 days (range 18–48, median 40 days). Clinical trial randomization and co-morbidities accounted for most cases of non-compliance. All 105 patients for whom chemotherapy was indicated received platin/taxane therapy, and 79/105 (75.2%) within 42 days (range 4–82, median 37 days). Venous thromboembolism prophylaxis was provided mechanically in 122/123 (99.2%) and pharmacologically in 99/123 (80.5%) patients within 24 hours of surgery. Prophylactic parenteral antibiotics were administered within 60 minutes of cytoreduction in 119/123 (96.7%) and discontinued within 24 hours after surgery in 120/123 (97.6%) cases.


Compliance with strict definitions of ovarian cancer quality indicators varies depending on the care delivered and documentation of that care. Increased attention to comprehensive surgical staging and timely initiation of chemotherapy appears warranted. With the move toward value-based payment models, quality indicators will play a significant role in health care delivery.

Biobank consent models – are we moving toward increased participant engagement in biobanking?

open access

 Abstract: Engagement, involvement, and active participation are buzzwords used in today's ethical debate on research biobanking. There are a variety of context-sensitive governance frameworks for research biobanks. However, many biobanks, especially large-scale population-based ones, seem to endorse a framework of broad consent, participation with minimal or no ongoing engagement, and no return of results. An alternative vision of involvement and active participation in this type of research has become increasingly visible in the literature. The problem, seen from the biobankers' perspective, is that the alternative vision might be costly, cumbersome, and risky, while the prevailing system for governance will maximize the scientific value of the biobank with minimal ethical, legal, and social efforts. Therefore, solid and convincing arguments are needed to determine if biobank institutions should take a radical step toward more ongoing engagement and donor involvement. In this paper, we review the arguments found in articles addressing dynamic consent, participatory research, reciprocity, and participant engagement in biobank research. We identify four core ideas on which the arguments for increased involvement are based. The strength of the arguments are then analyzed. We conclude that despite challenges with increased engagement, there seem to be substantial reasons to increase participant engagement in biobanking.

Keywords: biobank ethics, participatory research, dynamic consent, reciprocity
Download Article [PDF]

Doctors busy prolonging life have lost sight of end of life care - audio (25 min)

 CBC Radio
Oncologist Atul Gawande believes doctors spend so much time helping people live longer, they've neglected how to improve the quality of life at the end. (Tim-Llewellyn)
Listen 24:59

The Dr. Henry T. Lynch Symposium: Advances in Hereditary Cancer Sept 2015


 The Dr. Henry T. Lynch Symposium: Advances in Hereditary Cancer

Creighton University Health Sciences Continuing Education

Thursday, September 17, 2015 at 7:00 AM - Friday, September 18, 2015 at 5:00 PM (CDT) Omaha, NE

Survivor, Previvor, Family Member, Fellow, Resident, Full-Time Student Sep 7, 2015  Free   $0.00


Non-genetic cancer mechanism found - Akt pathway (Oncogene)

Cancer can be caused solely by protein imbalances within cells, a study of ovarian cancer has found. The discovery is a major breakthrough because, until now, genetic aberrations have been seen as the main cause of almost all cancer.

.....The research, led by scientists at the University of Leeds and The University of Texas MD Anderson Cancer Center, focused on the "Akt pathway," ( Protein kinase B (PKB), also known as Akt ) a signalling pathway within cells that drives cancer formation and the spread of cancers through the body......


Journal Reference:
  1. Z Timsah, Z Ahmed, C Ivan, J Berrout, M Gagea, Y Zhou, G N A Pena, Xin Hu, C Vallien, C V Kingsley, Y Lu, J F Hancock, J Liu, A B Gladden, G B Mills, G Lopez-Berestein, M-C Hung, A K Sood, M Bogdanov, J E Ladbury. Grb2 depletion under non-stimulated conditions inhibits PTEN, promotes Akt-induced tumor formation and contributes to poor prognosis in ovarian cancer. Oncogene, 2015; DOI: 10.1038/onc.2015.279

Too much, too late: Aggressive measures and the timing of end of life care discussions in women with gynecologic malignancies

Reviews timing and location of end of life discussions with gyn-oncology patients
Evaluates compliance with National Quality Forum (NQF) metrics of care
A high rate of inpatient and late end of life discussions is noted in this cohort.


This study describes the patterns of end of life (EOL) discussions and their impact on the use of aggressive measures in women with terminal gynecologic malignancies at a single institution.


An IRB-approved retrospective chart review identified 136 patients who died of gynecologic cancer between 2010 and 2012 with at least one interaction with their oncologists in the last 6 months of life. Aggressive measures were defined as chemotherapy within the last 14 days of life, emergency department (ED) visits, hospital and intensive care unit (ICU) admissions within the last 30 days of life, and inpatient deaths. The frequency and timing of EOL conversations were recorded. Utilization of hospice care was also described.


In the last 30 days of life, 54 (40%) patients were evaluated in the ED, 67 (49%) were admitted into hospital, and 16 (12%) were admitted to the ICU. Thirteen patients (10%) had chemotherapy in the last 14 days of life. Ninety-seven (71%) patients had a documented EOL conversation, eighteen (19%) as outpatients, and 79 (81%) as inpatients. Thirty (22%) patients died in the hospital. At the time of death, 55 (40%) patients were enrolled in outpatient hospice care. The mean amount of time in hospice was 28 days.


End of life care discussions rarely occurred in the outpatient setting or > 30 days before death. Inpatient encounters led to discussions about hospice and code status. Evaluation in the ED frequently resulted in escalation of care. Earlier EOL care discussions resulted in less aggressive measures.

Do All BRCA Mutations Come with the Same Cancer Risk?


Women born with mutations in the genes BRCA1 or BRCA2 have an increased risk of developing breast and ovarian cancer, but the degree of increase depends on a variety of factors.

Not all mutations within these genes raise the risk equally. A study published earlier this year tracked breast and ovarian cancer occurrences over a 75-year period in 31,000 women who had inherited mutations BRCA1 or BRCA2. The researchers found that mutations at either end of the BRCA1 gene increased the risk of breast cancer more than the risk of ovarian cancer. A group of mutations that occur in the middle portion of the gene, by contrast, raised ovarian cancer risk more than breast cancer risk.....

....Investigators at Dana-Farber are tracking the links between environment, heredity, and cancer in a study known as Project SEARCH.....

Cancer symptom awareness and barriers to symptomatic presentation in England[mdash]are we clear on cancer[quest]

open access

.... Women were significantly more likely than men to both recognise common cancer symptoms and to report barriers. Women were much more likely compared with men to report that fear would put them off from going to the doctor......Women were more likely than men to recognise each cancer symptom, except ‘persistent unexplained pain’.....

..... Finally, understanding the reasons why people in our sample identified certain barriers, for example, why people worry about wasting the doctor’s time, could further improve the effectiveness of future campaigns. Our findings could contribute to improving cancer survival in England to match the best in Europe by helping to develop targeted campaigns promoting early presentation of cancer symptoms.

BRCA1 and BRCA2 mutations sensitize to chemotherapy in patient-derived pancreatic cancer xenografts

open access

.... Clinical data in ovarian cancer show that patients with BRCA1 and BRCA2 mutations show higher response rates to treatment with cisplatin and other DNA-damaging agents resulting in improved outcome (Dann et al, 2012; Muggia and Safra, 2014). Similar observations have been made in case reports of patients with pancreatic cancer, suggesting that BRCA1 and BRCA2 mutations may sensitise to treatment with platinum drugs (Lowery et al, 2011; Sonnenblick et al, 2011). This is supported by preclinical studies using established pancreatic cancer cell lines (van der Heijden et al, 2005), and also by a large retrospective analysis of 71 pancreatic cancer patients with germline BRCA1 and BRCA2 mutations, where it was reported that patients with stage 3/4 disease who were treated with a platinum-containing regimen had a median survival of 22 months, compared with 9 months for those who did not receive platinum (Golan et al, 2014).
There are important unanswered questions concerning the optimum design of platinum-containing treatment protocols for this group of patients, as well as the role of newer agents such as inhibitors of poly-ADP-ribose polymerase (PARP) that have shown early promise in other cancer patients carrying germline BRCA mutations......

....Germline mutations in BRCA1 and BRCA2 result in defects in BRCA-mediated HR, which is important for the maintenance of genome stability (Venkitaraman, 2001; Gudmundsdottir and Ashworth, 2006). These mutations predispose to breast and ovarian cancers (Foulkes and Shuen, 2013; Kobayashi et al, 2013), and are associated with increased risk of pancreatic cancer (Fernandes et al, 1994; Klein et al, 2001; Bartsch et al, 2004; Grant et al, 2014). In addition to a role in tumour development, BRCA1 and BRCA2 mutations are associated with sensitivity to platinum drugs and other DNA-damaging agents in ovarian cancers (Dann et al, 2012; Muggia and Safra, 2014), and there are anecdotal reports that this is also the case in pancreatic cancers (Lowery et al, 2011; Sonnenblick et al, 2011).....

Tumour response, correlates of survival and clinical benefit

 Nature Reviews Clinical Oncology

 We are all familiar with the metrics of tumour shrinkage and time to the development of disease progression as important end points in clinical trials. This tenet is based on findings of numerous studies over several decades that have demonstrated a link between agents that cause tumour shrinkage in a cancer population and its correlation with an overall survival improvement. The problem is that the inevitable variation in how these definitions and criteria have been applied over many decades in clinical trials has led to different conclusions about the efficacy of a treatment. Added to this complexity are the following issues: non-measurable lesions, differences obtained with the method of assessment of progression (imaging versus clinical examination), changes in non-target lesions versus target lesions, impact of lesions that coalesce or split on treatment, to name but a few. When considering the additional complexities posed by these factors, it is perhaps not surprising that tumour response is often a poor indicator of survival outcome. Yet, how can this be reconciled to allow the field of oncology to move forward............

AllTrials US campaign officially launched

 29th July 2015
We are delighted to announce that today AllTrials USA has officially launched. Today 50 patient support groups, medical societies, universities and consumer groups are coming together to launch the AllTrials campaign in the US and to say:

“We are calling on everyone in our sector to join us in supporting the AllTrials campaign. Hundreds of thousands of patients have taken part in clinical trials which have never reported results. For every day that passes, more information is at risk of being lost forever. We have to make every clinical trial count. Join us today.”

See the list of US organisations that have joined here.


AllTrials – AllTrials US campaign officially launched

 29th July 2015
We are delighted to announce that today AllTrials USA has officially launched. Today 50 patient support groups, medical societies, universities and consumer groups are coming together to launch the AllTrials campaign in the US and to say:

“We are calling on everyone in our sector to join us in supporting the AllTrials campaign. Hundreds of thousands of patients have taken part in clinical trials which have never reported results. For every day that passes, more information is at risk of being lost forever. We have to make every clinical trial count. Join us today.”

See the list of US organisations that have joined here.

ecancer - Cancer and metabolism (special issue)


 Cancer and metabolism
Guest Editor: Luca Mazzarella

This special issue centres around the field of metabolism, which has become one of the hot topics of the moment, especially as applied to cancer.....

Special Issue articles

Special Issue: Lifestyle, nutrition and breast cancer: facts and presumptions for consideration

Special Issue: Oxidative stress and the unfulfilled promises of antioxidant agents

Special Issue: Metabolic serum biomarkers for the prediction of cancer: a follow-up of the studies conducted in the Swedish AMORIS study

Special Issue: Why does obesity promote cancer? Epidemiology, biology, and open questions

Why does obesity promote cancer?

open access

Special Issue

Why does obesity promote cancer? Epidemiology, biology, and open questions

 Keywords: obesity, body mass index, insulin, inflammation, DNA damage
The association between obesity and/or metabolic syndrome and an elevated mortality from cancer has been confirmed by an astonishing number of studies across nations and ethnicities, such that obesity is now recognised to be among the most prominent cancer risk factors worldwide.
Despite this overwhelming evidence and the societal impact of obesity, we know surprisingly little about the underlying molecular mechanisms. This knowledge gap is a major obstacle to the implementation of effective lifestyle change policies. As the scientific community is insecure on what messages it should deliver, administrators are uncertain as to what exactly to recommend, and consumers are confused about whom to believe. This leaves the field flooded with pseudo-scientific recommendations that are hard to eradicate.....

Gynaecological cancers (note: nothing on ovarian cancer)


The discourse on obesity and cancer has become dominant in public debate. Some aspects of this issue are clearly established beyond any reasonable doubt, namely the impact of obesity prior to diagnosis on specific cancer risks and on survivor outcome. Other aspects, such as the exact molecular mechanisms and the extent to which lifestyle changes can modify risk, still await definitive proof. Ultimately, the debate revolves on how much we can modify our cancer risk by intervening on the most basic of animal activities: nutrition. Some might find it tempting to dismiss this debate on the grounds that cancer risk (especially for those cancers where a single environmental factor cannot be identified) is mostly determined by ‘bad luck’, an un-escapable randomness in our stem cells’ DNA mutation accumulation rate [52]. It is clearly not so, but it is also true that our understanding of how nutrition impacts on cancer is far from complete. This creates fertile ground for the proliferation of pseudo-scientific recommendations and bogus ‘super healthy’ nutritional supplements. Likely, some mechanisms and specific lifestyle interventions may have stronger impact on specific cancers. It is also likely that an individual’s genetic makeup may influence response to diet, as we find variable genetic predisposition to specific cancers and genetically determined differences in metabolism. In the wave of medicine personalisation, it is not hard to imagine a future in which lifestyle plans will be tailored to individual risk profile and metabolism.

Is RMI a Useful Tool for Predicting Malignant Ovarian Masses in Developing Countries?

open access

Prognostic Value of Residual Disease after Interval Debulking Surgery for FIGO Stage IIIC and IV Epithelial Ovarian Cancer

open access

Pharmacological treatments for fatigue associated with palliative care

Cochrane: Featured Review (update)


To evaluate the efficacy of pharmacological treatments for fatigue in palliative care, with a focus on patients at an advanced stage of disease, including patients with cancer and other chronic diseases.

 Authors' conclusions

Based on limited evidence, we cannot recommend a specific drug for the treatment of fatigue in palliative care patients. Fatigue research in palliative care seems to focus on modafinil and methylphenidate, which may be beneficial for the treatment of fatigue associated with palliative care although further research about their efficacy is needed. Dexamethasone, methylprednisolone, acetylsalicylic acid, armodafinil, amantadine and L-carnitine should be further examined. Consensus is needed regarding fatigue outcome parameters for clinical trials.

Tuesday, July 28, 2015

Screening for pancreatic cancer in familial high-risk individuals: A systematic review

HRI = High Risk Individuals

open access

..... We chose familial HRIs as research subjects. In this population, there are also individuals with high risks for other diseases. Peutz-Jeghers syndrome with STK11/LKB1 gene mutation[36], hereditary pancreatitis with PRSS1 gene[37,38] or SPINK1 gene mutation[39], familial atypical multiple mole melanoma syndrome with CDKN2A or p16 gene mutations[40], hereditary breast ovarian cancer syndrome with BRCA2 and BRCA1 gene mutations[41,42], and Lynch syndrome with mismatch repair genes[43] are found in high risk populations, who should also receive attention. Nevertheless, these are not completely independent. Familial HRIs may also have gene mutations. The PRSS1 gene mutation is the main influencing factor in hereditary pancreatitis, an autosomal dominant disease. BRCA2 is one of the most common mutations, and was as high as 17% in one study[44]. Future studies on HRIs with gene mutations should be carried out to determine if they have a higher risk than HRIs without gene mutations. In addition, because of the complex nature of the pedigrees in pancreatic cancer, Wang et al[45] designed a tool known as PancPRO to identify familial HRIs, which was used for selecting and screening......
This is a good systematic review in which the authors analyzed the benefits and harms of pancreatic cancer screening in familial high-risk individuals. The results are interesting, and suggest that pancreatic cancer screening in familial HRIs can improve detection rate and prolong lifetime. In addition, it can influence psychological functions and increase the economic burden.

selected references (all references see article above)

36. (open access - pdf file link)
Giardiello FM, Brensinger JD, Tersmette AC, Goodman SN, Petersen GM, Booker SV, Cruz-Correa M, Offerhaus JA. Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology. 2000;119:1447-1453.[PubMed]

41. (open access)
Thompson D, Easton DF. Cancer Incidence in BRCA1 mutation carriers. J Natl Cancer Inst. 2002;94:1358-1365.[PubMed]
42. (open access)
van Asperen CJ, Brohet RM, Meijers-Heijboer EJ, Hoogerbrugge N, Verhoef S, Vasen HF, Ausems MG, Menko FH, Gomez Garcia EB, Klijn JG. Cancer risks in BRCA2 families: estimates for sites other than breast and ovary. J Med Genet. 2005;42:711-719.[PubMed] [DOI]

43. (open access)
Kastrinos F, Mukherjee B, Tayob N, Wang F, Sparr J, Raymond VM, Bandipalliam P, Stoffel EM, Gruber SB, Syngal S. Risk of pancreatic cancer in families with Lynch syndrome. JAMA. 2009;302:1790-1795.[PubMed] [DOI]

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



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

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

European Union Bans Hundreds of Drugs Over Clinical Trial Studies


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


CMAJl: Need to define patient engagement in research


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

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

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

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

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

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

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

Correspondence (open access)

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

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

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

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

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

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

FDA Alert

 July 27, 2015
Audience: Radiology

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

Monday, July 27, 2015

Management of Patients With a Genetic Variant of Unknown Significance


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


Pragmatic Randomized Trials Without Standard Informed Consent?


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

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

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



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

Study Design

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


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


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

Identifying novel hypoxia-associated markers of chemoresistance in ovarian cancer

open access


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

Sunday, July 26, 2015

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

 Blogger's Note: of interest to Lynch Syndrome patients

open access 


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

Late Breaking Abstracts deadline notice: ECCO/ESMO 2015

Late Breaking Abstracts Deadine Dates
 The European Cancer Congress 2015
My congress planner

Abstract submission open: 22 July 2015
Abstract submission deadline: 5 August 2015, 21:00 Central European time

Tea consumption and the incidence of cancer: a systematic review


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