Angiosarcomas of Primary Gynecologic Origin: A Clinicopathologic Review and Quantitative Analysis of Survival

Abstract

Objective:  Angiosarcomas are aggressive, malignant soft tissue neoplasms of endothelial origin and occur rarely in the female genital tract. There is lack of consensus on risk factors for poor outcome and optimal treatment. To this end, we performed a clinicopathologic review and survival analysis.

Conclusions: This review supports the use of surgical and adjuvant radiotherapy for angiosarcomas of the vulva, vagina, and uterus. Cytoreductive surgery and adjuvant chemotherapy remain the primary treatment of angiosarcomas of the ovary. 

K-Ras ovarian cancer - search results (past year)

Search results

(2009) KRAS mutation analysis in ovarian samples using a high sensitivity biochip assay

Full text 

Conclusion

In summary, KRAS mutation is a common event in ovarian cancer and is more frequently present in carcinoma of lower grade, lower FIGO stage, and in lesions of mucinous histotype. Our results support earlier findings from other groups in a very large number of samples. KRAS mutation was not found to be of prognostic value for patients under standard therapy, but these mutations could emerge as an important factor for individually tailored anti-EGFR therapies.

 

“Undruggable” Mutation Meets Its Match (K-Ras mutation)

news

  “K-Ras is considered to be the most important oncogene in cancer and is widely believed to be ‘undruggable,’” said Shokat. “We report the discovery of a new pocket on K-Ras that is druggable. We believe this has real translational implications for patients.”...

Women Who Are Prescribed Combination Hormone Replacement Therapy Should Use Caution When Taking Apigenin Supplements, MU Study Finds

Health News

"....During the study, laboratory rats were divided into four groups.....  

Health system costs not incurable but preventable | Evidence Network (Canada)

Evidence Network

"The tsunami metaphor is more and more often used in commentaries about the effect of aging on health care spending in Canada. It musters up images of devastation and irresistible strength submersing any levees the system might try to mount to oppose it. It is a powerful but misleading metaphor.
There is a worrying rise in health care spending in Canada, but it doesn’t have much to do with population aging. To stay with the oceanographic metaphor, aging might be, at most, a modest tidal wave. The real tsunami of health spending is the result of changes in the way all patients are treated in the system......
 

Extreme Nutrition: Can It Beat Cancer?

medscape

Editor's Note:
In this 2-part series, Medscape looks at diet as an essential therapeutic strategy for cancer patients. Part 1 focuses on the nutritional assessment of cancer patients, foods that help patients cope with side effects, and ways to make fortifying foods more appealing to the cancer-dulled appetite. Part 2 looks at extreme nutrition and the growing interest in fighting cancer with food....
 

Endometrioid ovarian carcinoma during pregnancy presenting with acute rupture

abstract

 

Background: Endometrioid ovarian carcinoma is rarely diagnosed during pregnancy and is generally asymptomatic. We present a case of endometrioid ovarian carcinoma during pregnancy that presented with acute rupture, and discuss options for management.  
Case: A primigravid woman presented at 26 weeks' gestation with severe abdominal pain. At laparotomy, an adnexal mass was found to have ruptured. The mass was identified postoperatively as an endometrioid ovarian carcinoma. The decision was made to perform Caesarean section with fertility-sparing surgical management at 34 weeks to maximize maternal and fetal outcomes.
Conclusion: To our knowledge, this is the first reported case of endometrioid ovarian carcinoma presenting with rupture in pregnancy. The differential diagnosis of severe abdominal pain during pregnancy should include rupture of ovarian malignancy.

 

Health News - Scientists investigate more effective ways to treat cancer

Health News 

Emotional and physical effects of cancer in life after treatment. ESCO conference highlight

video

Prof Annette Hasenburg - Universitätsklinikum Freiburg, Germany

Dr Annette Hasenburg talks to ecancer at the 2013 ESGO meeting about the psychological and physical effects of living with cancer and life after treatment.
Dr Hasenburg emphasises the need for more discussion between doctors and patients about the complexities of life after cancer and the changes to a patient’s personal life.
 

Update on the management and the role of intraperitoneal chemotherapy for ovarian cancer

abstract

PURPOSE OF REVIEW:

Ovarian cancer is the commonest gynaecological cancer and the fifth leading cause of cancer death in women worldwide. The majority of patients with ovarian cancer present at an advanced stage, and up to 70% of those treated with a curative approach eventually recur and succumb to their disease. This article examines the management of ovarian cancer over the years and the role of intraperitoneal chemotherapy in the treatment algorithm.

RECENT FINDINGS:

The surgical paradigm for ovarian cancer has changed and the goal is optimal cytoreduction with no residual disease. Intraperitoneal chemotherapy has been found to be superior to intravenous treatment alone, and the combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has produced encouraging results with improved disease-free and overall survivals at acceptable morbidity and mortality rates.

SUMMARY:

The most important prognostic factor for ovarian cancer survival is the ability to achieve optimal cytoreduction with no residual disease. CRS and HIPEC should be considered as an option for the management of advanced ovarian cancer and further trials are required to determine its role in both the primary and recurrent settings.

 

Prevalence and differentiation of hereditary breast and ovarian cancers in Japan

abstract

BACKGROUND:

We assembled needed data on the prevalence and characteristics of BRCA1/2 in Japan.

MATERIALS AND METHODS:

Our study of BRCA1/2 collected data at eight institutions in Japan on 320 individuals with a strong family history of breast cancer, according to the NCCN guidelines, by the end of March 2012.

RESULTS:

Among 260 proband cases, 46 (17.7 %) were positive for BRCA1, and 35 (13.5 %) were BRCA2-positive. Therefore, the total pathological mutation rate was 30.7 %. Pathology data after breast surgery were obtained from 37 cases of BRCA1 mutation, 23 (62.2 %) of which were triple negative (TN). On the other hand, 29 cases (82.9 %) of BRCA2 mutations were Luminal type. The most prevalent BRCA1 mutation site was L63X, found in 10 families. L63X was reported previously by studies in Japan, and it may be a founder mutation. We found two cases of large deletion detected by multiplex ligation-dependent probe amplification. One was an entire deletion of exon 20 and the lacked exons 1-9. TN with a family history of ovarian cancer was 11/20 (55 %). TN under 40-year-old (y.o.) 15/23 (65.2 %) and TN with one or more breast cancers in family history 17/32 (53.1 %) showed higher incidences of BRCA1 mutation.

CONCLUSION:

Hereditary breast and ovarian cancer (HBOC) may have nearly the same prevalence in Japan as in the US or Europe. If TN cases are taken into account, the ratio of BRCA1 is higher. L63X may be one of the founder mutations in Japan. A nationwide database of HBOC is important to develop risk models for BRCA1/2 carriers in Japan.

 

Risk-reducing surgery increases survival in BRCA1/2 mutation carriers unaffected at time of family referral

abstract

The aim of this study was to establish if risk-reducing surgery (RRS) increases survival among BRCA1/2 carriers without breast/ovarian cancer at the time of family referral. Female BRCA1/2 carriers were identified from the Manchester Genetic Medicine Database. Those patients alive and unaffected at the date of first family ascertainment were included in this study. Female first-degree relatives (FDRs) without predictive genetic testing who otherwise met eligibility criteria were also included. The effect of breast and ovarian RRS on survival was analysed. The survival experiences of RRS and non-RRS patients, stratified by BRCA status, were examined with Kaplan-Meier curves and contrasted using log-rank tests and Cox models. 691 female BRCA1/2 mutation carriers without breast or ovarian cancer at time of family ascertainment were identified; 346 BRCA1 and 345 BRCA2. 105 BRCA1 carriers and 122 BRCA2 carriers developed breast cancer during follow-up. The hazard of death was statistically significantly lower (P < 0.001) following RRS versus no RRS. 10-year survival for women having RRS was 98.9 % (92.4-99.8 %) among BRCA1 and 98.0 % (92.2-99.5 %) among BRCA2 carriers. This survival benefit with RRS remained significant after FDRs were added. Women who had any form of RRS had increased survival compared to those who did not have RRS; a further increase in survival was seen among women who had both types of surgery. However, formal evidence for a survival advantage from bilateral mastectomy alone requires further research.

 

Table of Contents — November 2013 11th Annual Meeting of the Japanese Society of Medical Oncology, 29–31 August 2013, Sendai, Japan

Table of Contents

External validation of three prognostic models for overall survival in patients with advanced-stage epithelial ovarian cancer

Abstract

Background:

For various malignancies, prognostic models have shown to be superior to traditional staging systems in predicting overall survival. The purpose of this study was to validate and compare the performance of three prognostic models for overall survival in patients with advanced-stage epithelial ovarian cancer.

Methods:

A multi-institutional epithelial ovarian cancer database was used to identify patients and to evaluate the predictive performance of two nomograms, a prognostic index and FIGO (International Federation of Obstetrics and Gynecology) stage. All patients were treated for advanced-stage epithelial ovarian cancer between January 1996 and January 2009 in 11 hospitals in the eastern part of The Netherlands.

Results:

In total, 542 patients were found to be eligible. Overall performance did not differ between the three prognostic models and FIGO stage. The discriminative performance for Chi’s model was moderately good (c indices 0.65 and 0.68) and for the models of Gerestein and Teramukai reasonable (c indices between 0.60 and 0.62). The c indices of FIGO stage ranged between 0.54 and 0.62. After recalibration, the three models showed almost perfect calibration, whereas calibration of FIGO stage was reasonable.

Conclusion:

The three prediction models showed general applicability and a reasonably well-predictive performance, especially in comparison to FIGO stage. To date, there are no studies available that analyse the impact of these prognostic models on decision-making and patient outcome. Therefore, the usefulness of these models in daily clinical practice remains to be investigated.

To read this article in full you may need to log in, make a payment or gain access through a site license (see right).

 

Analysis of the contribution of immunologically-detectable HER2, steroid receptors and of the "triple-negative" tumor status to disease-free and overall survival of women with epithelial ovarian cancer

Abstract

We assessed associations between steroid receptors including: estrogen-alpha, estrogen-beta, androgen receptor, progesterone receptor, the HER2 status and triple-negative epithelial ovarian cancer (ERα-/PR-/HER2-; TNEOC) status and survival in women with epithelial ovarian cancer. The study included 152 women with primary epithelial ovarian cancer. The status of steroid receptor and HER2 was determined by immunohistochemistry. Disease-free and overall survival were calculated and compared with steroid receptor and HER2 status as well as clinicopathological features using the Cox Proportional Hazards model. A mean follow-up period of 43.6 months (interquartile range=41.4 months) was achieved where 44% of patients had serous tumor, followed by mucinous (23%), endometrioid (9%), mixed (9%), undifferentiated (8.5%) and clear cell tumors (5.3%). ER-alpha staining was associated with grade II-III tumors. Progesterone receptor staining was positively associated with a Body Mass Index≥25. Androgen receptor positivity was higher in serous tumors. In stand-alone analysis of receptor contribution to survival, estrogen-alpha positivity was associated with greater disease-free survival. However, there was no significant association between steroid receptor expression, HER2 status, or TNEOC (ERα-/PR-/HER2-; TNEOC) status, and overall survival. Although estrogen-alpha, androgen receptor, progesterone receptor and the HER2 status were associated with key clinical features of the women and pathological characteristics of the tumors, these associations were not implicated in survival. Interestingly, women with TNEOC seem to fare the same way as their counterparts with non-TNEOC.
 

Surgical Management of Peritoneal Surface Malignancy with Respect to Tumour Type, Tumour Stage and Individual Tumour Biology

abstract

Peritoneal tumour dissemination is still considered as a terminal disease. For the last two decades, cytoreductive surgery (CRS) combined with intraoperative hyperthermic chemotherapy (HIPEC) has been popularised by Paul Sugarbaker almost doubling survival in selected patients compared with systemic chemotherapy alone. Nowadays, this particular treatment protocol is available in comprehensive cancer centres with reasonable mortality and morbidity. However, patient selection is still challenging. In general, CRS and HIPEC is indicated in primary peritoneal tumours such as mesothelioma and pseudomyxoma peritonei as well as in peritoneal metastases derived from gastrointestinal malignancies and ovarian cancers. Since systemic tumour spread is uncommon in patients with peritoneal metastases, peritoneal tumour dissemination was defined as localised disease within the "compartment abdomen". However, CRS and HIPEC are only beneficial as long as complete cytoreduction is achieved (CC-0 or CC-1). Histopathological parameters, the Sugarbaker peritoneal carcinomatosis index (PCI) and general condition of the patient have been established as patient selection criteria. In primary peritoneal cancers, individual tumour biology is the predominant criterium for patient selection as opposed to intraabdominal tumour load in peritoneal metastases derived from gastrointestinal cancers. In gastric cancer, CRS and HIPEC should be restricted to synchronous limited disease because of its biological aggressiveness. In patients with free floating cancer cells without macroscopic signs of peritoneal spread, however, CRS and HIPEC following preoperative "neoadjuvant" chemotherapy preserves chances for cure. So far, there is no general recommendation for CRS and HIPEC by clinical practice guidelines. In the recent S3 guideline for treatment of colorectal cancer, however, CRS and HIPEC have been included as possible treatment options.

 

Evaluation after five years of the cancer genetic counselling programme of Valencian Community (Eastern Spain)

abstract

 To evaluate the cancer genetic counselling programme in Valencian Community using intermediate indicators. Descriptive analysis of organisational and effectiveness indicators from the start in 2005 until December 2010: correct referral of patients according to the area from where they were referred (primary or hospital-based care) and syndrome; families identified as having each syndrome; suitability of the genetic testing for individuals with a cancer diagnosis (index cases, IC) and relatives of ICs with mutations; family size; and results of genetic testing on genes, ICs and relatives. 9,942 individuals attended, 87.7 % were referred by hospital-based care and 8.4 % by primary care. 7,516 patients (79 %) fulfilled cancer genetic counselling criteria (82 % from hospital-based care and 46 % from primary care). Amongst those who fulfilled the criteria, 59 % of referrals were related to hereditary breast ovarian cancer syndrome and 32 % to hereditary non-polyposis colorectal cancer. ICs were found in 3,082 families (78.7 %) and genetic testing was carried out on 91.3 % of them. Pathogenic mutations were detected in 21.8 % of the ICs and the testing was then offered to their relatives (an average of 3 per IC). Pathogenic mutations were found in 54 % of the assessed relatives. Results in 5 years confirm the appropriateness of these facilities, as part of an integrated health service, to identify families and individuals with genetic risk to offer them personalized counselling. Improvements have to be made with regard to the information given to both health professionals and patients about the risk criteria for various syndromes

Serum protein profile at remission can accurately assess therapeutic outcomes and survival for serous ovarian cancer

open access/full free text

Abstract

BACKGROUND:

Biomarkers play critical roles in early detection, diagnosis and monitoring of therapeutic outcome and recurrence of cancer. Previous biomarker research on ovarian cancer (OC) has mostly focused on the discovery and validation of diagnostic biomarkers. The primary purpose of this study is to identify serum biomarkers for prognosis and therapeutic outcomes of ovarian cancer.

EXPERIMENTAL DESIGN:

Forty serum proteins were analyzed in 70 serum samples from healthy controls (HC) and 101 serum samples from serous OC patients at three different disease phases: post diagnosis (PD), remission (RM) and recurrence (RC). The utility of serum proteins as OC biomarkers was evaluated using a variety of statistical methods including survival analysis.

RESULTS:

Ten serum proteins (PDGF-AB/BB, PDGF-AA, CRP, sFas, CA125, SAA, sTNFRII, sIL-6R, IGFBP6 and MDC) have individually good area-under-the-curve (AUC) values (AUC = 0.69-0.86) and more than 10 three-marker combinations have excellent AUC values (0.91-0.93) in distinguishing active cancer samples (PD & RC) from HC. The mean serum protein levels for RM samples are usually intermediate between HC and OC patients with active cancer (PD & RC). Most importantly, five proteins (sICAM1, RANTES, sgp130, sTNFR-II and sVCAM1) measured at remission can classify, individually and in combination, serous OC patients into two subsets with significantly different overall survival (best HR = 17, p<10(-3)).

CONCLUSION:

We identified five serum proteins which, when measured at remission, can accurately predict the overall survival of serous OC patients, suggesting that they may be useful for monitoring the therapeutic outcomes for ovarian cancer.

 

Annexin A4 Is Involved in Proliferation, Chemo-Resistance and Migration and Invasion in Ovarian Clear Cell Adenocarcinoma Cells

open access (technical)

 ..... CCC is the second most common EOC subtype after HGSC. More than 50% of inactivating mutations in the AT-rich interactive domain 1A gene (ARID1A), almost 40% of activating mutations in the gene encoding the catalytic subunit of phosphatidylinositol 3-kinase (PIK3CA), and microsatellite instability characterize the genetic alterations in CCC [1]. A recent large-cohort study found a pattern in CCC of resistance to standard platinum-based chemotherapy, which offers poor prognosis for patients diagnosed in advanced clinical stages (i.e., International Federation of Gynecology and Obstetrics stages III and IV) [2]. The ratio of CCC among EOC in Japan is reported to be higher than that in Western countries (15–25% and 5–12%, respectively); ethnic or geographical differences in its incidence have also been noticed [3]......

Results

ANXA4 was highly expressed in CCC specimens

Images corresponding to each representative IHC score and a summary of the results are shown in Figure 1A and B. All 52 CCC specimens demonstrated significant staining for ANXA4 (IHC score 5 or 6) without exception, with P<0.05 against all other types of ovarian carcinomas and LMP tumors (Figure 1B). In carcinoma cases, although few cases were available for IHC, all four mucinous carcinomas and two of six endometrioid carcinomas showed high levels (IHC score 4 or greater) of ANXA4 expression. Conversely, all three poorly or undifferentiated carcinomas and 13 of 14 SC expressed no detectable ANXA4. Only two mucinous adenomas were examined, but both of them showed an IHC score 6 expression of ANXA4, presenting a similarity to their malignant counterpart. Only one case of normal premenopausal ovary was available for IHC, but no ovarian components, including surface epithelium, follicles, and stromal tissues, were reactive for ANXA4.....

Is the Two-Tier Ovarian Serous Carcinoma Grading System Potentially Useful in Stratifying Uterine Serous Carcinoma? A Large Multi-Institutional Analysis

abstract

Highlights

•

140 patients with uterine serous carcinoma from three academic institutions were studied.

•

All cases were graded using MDACC two-tier grading system as low grade and high grade

•

The prognostic utility of application of MDACC two-tier grading system to uterine serous carcinoma is not applicable

---

Objective

A subset of uterine serous carcinoma (USC) may have better clinical behavior bringing up the possibility that there may be morphologic features, which would help in their categorization. The aim of this study is to evaluate the potential use of the MD Anderson Cancer Center 2-tier grading system for ovarian carcinoma in USC.

Conclusion

The presence of atypia and mitosis across a uterine serous carcinoma is notoriously variable in magnitude and extent, potentially making evaluation of these features difficult and subsequent grading subjective. Our findings thus show that actual prognostic utility of application of MDACC two-tier grading system to uterine serous carcinoma may not be applicable
 

Pulse-Voices from the Heart of Medicine

Welcome 

Pulse reveals the personal side of health care through stories, poems and images. On this page--our current and most recent offerings.

What is Pulse?

Every Friday, Pulse--voices from the heart of medicine publishes and distributes a first-person story or poem about giving or receiving health care.
Launched in 2008, Pulse was created by members of the Department of Family and Social Medicine at Montefiore Medical Center and Albert Einstein College of Medicine in collaboration with colleagues and friends around the country.
Pulse's goal is to tell the story of health care through the personal experiences of those who live it--patients, health professionals, students and caregivers. At a time when medicine is often criticized for being cold and oblivious, Pulse aims to highlight the human and vulnerable face of medicine in order to promote the humanistic practice of medicine and encourage advocacy for a compassionate system of health care for all.
Since its launch, Pulse has drawn the attention of the national media and policymakers. Widely used in medical education to promote humanism and professionalism, Pulse is read by both health professionals and non-health professionals who are drawn by its diverse voices, by its strong writing and by its authenticity.
Pulse welcomes submissions by anyone who has a healthcare-related story to tell.

 

Profile of panobinostat and its potential for treatment in solid tumor

open access

Ovarian cancer
Observations in preclinical studies using several human ovarian cancer cell lines have identified panobinostat to have synergistic effects with drugs commonly used to treat ovarian cancer, such as gemcitabine, paclitaxel, docetaxel, and 5′-DFUR (metabolite of capecitabine).57,58 Additionally, the treatment of panobinostat in combination with cisplatin of ovarian cancer previously resistant to cisplatin may be a viable treatment option based upon preclinical data showing that the presence of panobinostat lowered the inhibitory concentration for cisplatin in previously cisplatin resistant ovarian cancer cell lines.59 

E2 and LDX for the Treatment of Cognitive Complaints After Oophorectomy

ClinicalTrials.gov

This study is currently recruiting participants.

Verified November 2013 by University of Pennsylvania

Sponsor:

University of Pennsylvania

Information provided by (Responsible Party):

C. Neill Epperson, University of Pennsylvania

ClinicalTrials.gov Identifier:

NCT01986764

First received: October 30, 2013

Last updated: November 11, 2013

Last verified: November 2013

 
Purpose

This project seeks to address cognitive disturbance, which is a frequent adverse sequelae of risk reducing bilateral salpingo-oophorectomy (RRSO) with or without post-procedure chemotherapy and adjunctive treatments. RRSO after completion of childbearing is recommended for prevention of ovarian and breast cancer in women with BRCA1/BRCA2 mutations and standard of care for women with some forms of hormone-responsive cancer. Knowledge regarding the impact of this procedure, with or without chemotherapy, and subsequent hypogonadism on brain health is less than adequate. Premenopausal women who undergo an acute surgical menopause are at greater risk for verbal memory decline and executive function (EF) complaints, but as of yet, we cannot predict who is going to experience these adverse sequelae, nor do we have targeted prevention or treatment strategies other than hormone therapy, which is not an option in many cases and not always effective. An idealized sample as women who are planning for a RRSO will undergo brain imaging and behavioral assessments pre- and post-surgery as well as pre-/post-treatment with E2 or the psychostimulant, lisdexamphetamine (LDX; Vyvanse®).

Condition	Intervention
Planned RRSO	Drug: LDX Drug: Estradiol Drug: Placebo

End-of-life care pathways for the dying (lack of evidence) Cochrane Review update

Cochrane Summaries

Background
End-of-life pathways are used for people who are in the last days of their life to guide care, aid decision making and provide efficient care. This review examined whether using end-of-life care pathways in caring for the dying was effective.
Study characteristics
We searched scientific databases for clinical trials in which the effect of the end-of-life care pathway was compared with a control group that received usual care or with trials comparing one end-of-life care pathway with another end-of-life care pathway. Participants were to be patients, carers and families who received care guided by an end-of-life care pathway. There were no restrictions on age of the patient, diagnosis or setting (hospital, home, nursing home).
Key results
We found no studies fitting our criteria.
Quality of evidence
We could not locate any high-quality controlled studies that could answer this important question; despite concerns about the Liverpool Care Pathway (the most commonly used end-of-life care pathway). It is important for health services to base their care on high-quality evidence. Until such evidence is available, the use of end-of-life care pathways should be avoided. Large randomised controlled trials (where patients are allocated to treatments or groups using a random method) or other well-designed controlled studies are required for evaluating the use of end-of-life care pathways in caring for dying people in various clinical settings. Future studies should measure positive as well as negative outcomes for patients, families, carers and health professionals.
- See more at: http://summaries.cochrane.org/CD008006/end-of-life-care-pathways-for-the-dying#sthash.1jAPsEWh.dpuf

Main results: 

The original review identified 920 titles. The updated search found 2042 potentially relevant titles (including the original 920), but no additional studies met criteria for inclusion in the review update.

Authors' conclusions: 

With sustained concerns about the safety of the pathway implementation and the lack of available evidence on important patient and relative outcomes, recommendations for the use of end-of-life pathways in caring for the dying cannot be made. Since the last version of this review, no new studies met criteria for inclusion in the review update. With recently documented concerns related to the potential adverse effects associated with Liverpool Care Pathway (the most commonly used end-of-life care pathway), we do not recommend decision making based on indirect or low-quality evidence. All health services using end-of-life care pathways are encouraged to have their use of the pathway, to date, independently audited. Any subsequent use should be based on carefully documented evaluations. Large RCTs or other well-designed controlled studies are urgently required for the evaluation of the use of end-of-life care pathways in caring for dying people in various clinical settings. In future studies, outcome measures should include benefits or harms concerning the outcomes of interest in this review in relation to patients, families, carers and health professionals.

- See more at: http://summaries.cochrane.org/CD008006/end-of-life-care-pathways-for-the-dying#sthash.1jAPsEWh.dpuf

PD-1 targeting in cancer immunotherapy

open access

"....It is interesting to note that the anti–PD-1 MoAb demonstrated clinical objective responses in patients with previously presumed “nonimmunogenic” tumor types, including non-small cell lung cancer (NSCLC) and ovarian cancer, in whom durable partial responses (PRs) and stable disease were observed.[10] ....

Sequencing study underscores difficulty of treating ovarian cancer, points to diverse patterns of ovarian cancer evolution

Medical News Today

"One of the most comprehensive studies of genetic mutations in ovarian cancer has been published, demonstrating an unprecedented level of genetic variation that exists in both primary tumors and metastatic lesions of ovarian cancer. The study highlights potential new pathways for therapeutic intervention and suggests that sampling and sequencing of multiple disease sites may be required for effective targeted treatments.
The paper, titled "Genomic and transcriptomic plasticity in treatment-naïve ovarian cancer," is available online at the journal Genome Research and is authored by scientists at the University Medical Center Utrecht in The Netherlands and Life Technologies Corporation in Carlsbad, Calif. With an annual global incidence of 220,000 and mortality of 140,0001, ovarian cancer is a leading cause of cancer deaths in women, making it a disease in urgent need of improved treatment.
The researchers examined a total of 27 archived tumor biopsy samples, both from primary tumors as well as distant metastatic sites, gathered from three women with late stage (IIIC/IV) ovarian cancer. Tumor samples and matched normal tissue samples were analyzed using a variety of methods, including transcriptome and mate-pair sequencing and several targeted gene sequencing panels. Sequencing was conducted on the Applied Biosystems® SOLiD 5500xL and Ion Personal Genome Machine (PGM™), both from Life Technologies, using Life's Ion AmpliSeq™ Comprehensive Cancer Panel, a panel of more than 400 genes that have been implicated in cancer. This study represents the first peer-reviewed, scientific publication employing this panel of 409 oncogenes.....
 

Retrospective analysis of outcomes of secondary debulking surgery for recurrent epithelial ovarian cancer with favorable prognostic factors

abstract

Aim

Ovarian cancer is the second most common gynecological malignancy, yet it has the highest case-fatality ratio of all gynecologic malignancies. Surgery followed by combination platinum-taxane chemotherapy is the standard approach to the management of primary epithelial ovarian cancer. However, standard treatment of patients with recurrent ovarian cancer remains poorly defined. Secondary cytoreductive surgery (SDS) at the time of relapse has been proposed as a means of improving the prognosis of recurrent ovarian cancer patients with a treatment-free interval of at least 6 months.

Methods

In the present study, we retrospectively collected 16 patients with recurrent epithelial ovarian cancer who might benefit most from SDS and evaluated the impact of SDS on the outcomes for this highly select patient group.

Results

We found that SDS led to excellent outcomes, with a 73.1% 8-year overall survival rate after initial treatment, a 67.9% 5-year overall survival rate after prior SDS, and a 31.3% 5-year progression-free survival rate after prior SDS. Although the findings were not significant, these results suggest that repeated SDS might improve outcomes for this patient group.

Conclusion

The present study may provide a platform for discussion of the impact of aggressive or repeated SDS on the survival of patients with recurrent epithelial ovarian cancer and favorable prognostic factors. Further multi-institutional studies with larger number of patients are mandatory to confirm the present findings.

 

SIS - Sisters In Survival - "tomorrow is not an option"

Sisters In Survival

What We Do

Sisters in Survival works directly with gynecologic oncologists, medical imaging centers, and other community partners to provide medications and diagnostic procedures to ovarian cancer patients who, otherwise, could not afford them. Ovarian cancer is an equal opportunity enemy. It does not strike based on one’s ability to pay. While some can afford to fight it head-on with everything in the medical arsenal, others are forced to forgo anti-nausea medications because—even with insurance—they can’t afford the high cost of the co-payments. Sisters In Survival is an all volunteer, donation-driven organization. Over ninety-seven percent of the money we receive goes toward providing treatment and diagnostics to patients who need help now…today. Tomorrow is not an option

 

Navigating uncharted waters: a guide to shared decision making

Patient-Voice 

'Nothing about us without us’ has been the rallying call for cancer advocacy that has helped to expose the lack of patient voices in decisions about care and treatments. Since the 1990s, enlightened doctors and healthcare organisations, aware of the hierarchical nature of the physician–patient relationship, have joined the movement to better inform people so they can be part of decisions, and the result is that in many countries the picture has radically improved. There is no doubt that attitudes about truth telling and provision of information – as witnessed by the proliferation of patient decision aids and websites – have changed for the better.

In turn, this has led to the rise of shared decision making (SDM) – which is defined, briefly, as involving a patient in a decision to the extent they would wish by providing and discussing information about options. It has become a topic that has attained specialist status, at least when judged by the number of research groups, conferences and organisations reporting and adopting shared decision making.

In 2010 the Salzburg Statement on Shared Decision Making was agreed at a global seminar (http://tiny.cc/SDM), which issued a call to clinicians, policymakers and patients to work together..... 

Associations between health care seeking and socioeconomic and demographic determinants among people reporting alarm symptoms of cancer: a population-based cross-sectional study

Abstract

Elevated Plasma Vitamin B12 Levels as a Marker for Cancer: A Population-Based Cohort Study

open access

In conclusion, our study showed that high plasma Cbl (cobalamin) levels increased the risk of subsequently diagnosed cancer, mostly within the first year of follow-up. However, this association was not present for all cancer types. Although our results may have clinical implications for interpreting high Cbl levels, further studies are warranted to examine the possible diagnostic value of high plasma Cbl levels.  

Tumor Growth Rate (TGR) is an early indicator of anti-tumor drug activity in phase I clinical trials

abstract

Purpose: RECIST evaluation does not take into account the pre-treatment tumor kinetics and may provide incomplete information regarding experimental drug activity. Tumor Growth Rate (TGR) allows for a dynamic and quantitative assessment of the tumor kinetics. How TGR varies along the introduction of experimental therapeutics and is associated with outcome in phase I patients remains unknown. 

Experimental designs: Medical records from all patients (n=253) prospectively treated in 20 phase I trials were analyzed. TGR was computed during the pre-treatment period (REFERENCE) and the EXPERIMENTAL period. Associations between TGR, standard prognostic scores (RMH score) and outcome (PFS, OS) were computed (multivariate analysis). 

Results: We observed a reduction of TGR between the REFERENCE vs. EXPERIMENTAL periods (38% vs. 4.4%, P<.00001). Although most patients were classified as stable disease (65%) or progressive disease (25%) by RECIST at the first evaluation, 82% and 65% of them exhibited a decrease in TGR, respectively. In a multivariate analyses, only the decrease of TGR was associated with PFS (P=.004), whereas the RMH score was the only variable associated with OS (P=.0008). Only the investigated regimens delivered were associated with a decrease of TGR (P<.00001, multivariate analysis). Computing TGR profiles across different clinical trials reveals specific patterns of antitumor activity. 

Conclusions: Exploring TGR in phase I patients is simple and provides clinically relevant information: (i) an early and subtle assessment of signs of antitumor activity; (ii) independent association with PFS; and (iii) It reveals drug-specific profiles; suggesting potential utility for guiding the further development of the investigational drugs.

 

Germline and Somatic Mutations in Homologous Recombination Genes Predict Platinum Response and Survival in Ovarian, Fallopian Tube, and Peritoneal Carcinomas

abstract

Purpose: Hallmarks of germline BRCA1/2-associated ovarian carcinomas include chemosensitivity and improved survival. The therapeutic impact of somatic BRCA1/2 mutations and mutations in other homologous recombination (HR) DNA repair genes is uncertain. 

Experimental Design: Using targeted capture and massively parallel genomic sequencing, we assessed 390 ovarian carcinomas for germline and somatic loss-of-function mutations in 30 genes, including BRCA1, BRCA2, and 11 other genes in the HR pathway. 

Results: 31% of ovarian carcinomas had a deleterious germline (24%) and/or somatic (9%) mutation in one or more of the 13 HR genes: BRCA1, BRCA2, ATM, BARD1, BRIP1, CHEK1, CHEK2, FAM175A, MRE11A, NBN, PALB2, RAD51C, and RAD51D. Non-serous ovarian carcinomas had similar rates of HR mutations to serous carcinomas (28% vs. 31%, p=0.6), including clear cell, endometrioid, and carcinosarcoma. The presence of germline and somatic HR mutations was highly predictive of primary platinum sensitivity (p=0.0002) and improved overall survival (p=0.0006), with median overall survival 66 months in germline HR mutation carriers, 59 months in cases with a somatic HR mutation, and 41 months for cases without an HR mutation. 

Conclusions: Germline or somatic mutations in HR genes are present in almost one-third of ovarian carcinomas, including both serous and non-serous histologies. Somatic BRCA1/2 mutations and mutations in other HR genes have a similar positive impact on overall survival and platinum responsiveness as germline BRCA1/2 mutations. The similar rate of HR mutations in non-serous carcinomas supports their inclusion in PARP inhibitor clinical trials.

 

Illness Is Personal!

The ASCO Post

Ocular adverse events of molecularly targeted agents approved in solid tumours: A systematic review

abstract

When using molecularly targeted agents (MTAs), oncologists and patients face new and sometimes unexpected toxicities. Though ocular adverse events (OAEs) are not uncommon with chemotherapy, they are rarely severe or dose limiting. Ocular toxicity profile may differ with MTAs, indeed severe and dose limiting toxicities have been described with targeted therapies currently under investigation. Our study aimed to review OAEs experienced with MTAs approved in solid tumours. This review revealed that many OAEs, frequent and potentially severe, exist and concern most MTAs. The suggestion is prompt referral of patients with severe pain and/or visual impairment to the ophthalmologist since these symptoms can be associated with potentially severe OAE and need ophthalmic assessment. Oncologists must be aware of such events and their potential severity for better treatment and better diagnosis in daily practice as well as in clinical trials. 

Table 1.(requires subscription to view/+other tables)
Characteristics of molecularly targeted agents reviewed and description of analysed reports.

FDA, U.S. Food and Drug Administration; EMA, European Medicines Agency; Mab, Monoclonal antibody; TKI, Tyrosine Kinase Inhibitor; SR, Soluble Receptor; STKI, Serine-Threonine Kinase Inhibitor; EGFR, Epidermal Growth Factor Receptor; HER2, Human Epidermal Growth Factor Receptor 2; VEGF, Vascular Endothelial Growth Factor; VEGFR, Vascular Endothelial Growth Factor Receptor; PDGFR, Platelet-Derived Growth factor Receptor; FGFR, Fibroblast Growth factor Receptor; Kit, Stem cell factor receptor (or C-Kit or CD117); FLT-3, Fms-like tyrosine kinase-3; CSF-1R, Colony Stimulating Factor Receptor Type 1; RET, glial cell-line derived neurotrophic factor receptor; cMet, Hepatocyte Growth Factor Receptor; mTOR, mammalian Target Of Rapamycin; ALK, Anaplastic Lymphoma Kinase; CTLA-4, Cytotoxic T-Lymphocyte-Associated Antigen 4; MEK, Mitogen-activated Extracellular signal regulated Kinase; BP, Binding Protein; SMO, Smoothened transmembrane protein of the Hedgehog pathway.

Health News - Chronic Diseases Hinder Good Cancer Survival Rates

Health News

Body's natural defence carries early warning system for recurring cancers

Health News 

Trabectedin plus pegylated liposomal doxorubicin: the return of a treatment option for ovarian cancer (+other)

Future Oncology, Future Medicine

Future Oncology

December 2013

Sections:

Manufacturing difficulties resulted in a shortage of pegylated liposomal doxorubicin (PLD), but these problems have recently been resolved and PLD is now available again. It follows that oncologists now have access to this important anticancer therapy and the combination of trabectedin (Yondelis^®, PharmaMar, Madrid, Spain) plus PLD can once more be prescribed for the treatment of relapsed ovarian cancer, the topic under discussion at this symposium.

Today we have a much greater understanding regarding which patients with ovarian cancer in particular will benefit the most from treatment with trabectedin plus PLD:

	▪ The first group involves patients with partially platinum-sensitive disease;
	▪ The second group includes patients fully platinum-sensitive but who, for whatever reason, cannot be retreated with platinum therapy.

These are important clinical problems that oncologists have to deal with in their daily practice and in this symposium we count on eminent experts in the field to present some of the most recent data on these topics under the chairmanship of Andres Poveda (Instituto Valenciano de Oncología, Valencia, Spain) and Eric Pujade-Lauraine (Hôpital Hôtel-Dieu, París, France). Key speakers at the symposium are Nicoletta Colombo (European Institute of Oncology, University of Milan, Bicocca, Milan, Italy), Maurizio D‘Incalci (IRCCS – Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy), Antonio González (MD Anderson Cancer Center, Madrid, Spain) and Isabel Ray-Coquard (Centre Léon Bérard, Lyon, France). To discuss the findings that are presented with the goal of providing an overall perspective we have the following experts: Jalid Sehouli (European Competence Center for Ovarian Cancer, Charité University Hospital, Berlin, Germany), Josep M del Campo (Vall d‘Hebron University Hospital, Barcelona, Spain) and Domenica Lorusso (Fondazione `IRCCS‘ National Cancer Institute, Milan, Italy).

Users who read this article also read:

Optimizing treatment of the partially platinum-sensitive ovarian cancer patient Nicoletta Colombo Future Oncology, Dec 2013, Vol. 9, No. 12s, Pages 19-23. Summary | Full Text | PDF (493 KB) | PDF Plus(494 KB) | Add to Favorites | Related  | Reprints & Permissions

Increasing the chances for platinum-sensitive ovarian cancer patients Antonio González Future Oncology, Dec 2013, Vol. 9, No. 12s, Pages 29-35. Summary | Full Text | PDF (946 KB) | PDF Plus(947 KB) | Add to Favorites | Related  | Reprints & Permissions

Trabectedin mechanism of action: what’s new? Maurizio D’Incalci Future Oncology, Dec 2013, Vol. 9, No. 12s, Pages 5-10. Summary | Full Text | PDF (1476 KB) | PDF Plus(1477 KB) | Add to Favorites | Related  | Reprints & Permissions

Discussion: session 1 (requires subscription) What are the benefits of extending the platinum-free interval? What is the importance of the sequence of treatment? Jalid Sehouli, Josep M del Campo, Domenica Lorusso Future Oncology, Dec 2013, Vol. 9, No. 12s, Pages 25-27. Citation | Full Text | PDF (367 KB) | PDF Plus(367 KB) | Add to Favorites | Related  | Reprints & Permissions

 

Biology of ovarian cancer and trabectedin mechanism of action, Future Oncology, Future Medicine

abstract

Symposium Paper

More than 50% of patients with ovarian cancer have genetic alterations in the homologous repair pathway. Trabectedin  (Herceptin)appears to induce damage more readily in tumor cells with defects in the homologous repair system. Moreover, trabectedin inhibits monocyte differentiation into tumor-associated macrophages and inhibits the production of inflammatory mediators such as IL-6. In patients with platinum-sensitive, relapsed ovarian cancer, trabectedin plus pegylated liposomal doxorubicin was associated with a trend towards improved overall survival by extending the platinum-free interval. These clinical effects could possibly be attributed to actions of trabectedin on the tumor microenvironment (e.g., a reduction of IL-6). Thus, trabectedin is an agent with mechanisms of action especially appropriate for targeting key processes in the biology of ovarian cancer.

 

Pharmacokinetics and Imaging of 212Pb-TCMC-Trastuzumab After Intraperitoneal Administration in Ovarian Cancer Patients

abstract

Purpose: Study distribution, pharmacokinetics, and safety of intraperitoneal (IP) ²¹²Pb-TCMC-trastuzumab in patients with HER-2-expressing malignancy.

Experimental Design: IP ²¹²Pb-TCMC-trastuzumab was delivered, after 4 mg/kg intravenous (IV) trastuzumab (Herceptin), to 3 patients with HER-2-expressing cancer who had failed standard therapies. Patients were monitored for toxicity and pharmacokinetics/dosimetry parameters.

Results: Imaging studies after 0.2 mCi/m² (7.4 MBq/m²) show little redistribution out of the peritoneal cavity and no significant uptake in major organs. Peak blood level of the radiolabeled antibody, determined by decay corrected counts, was <23% injected dose at 63 hours; maximum blood radioactivity concentration was 6.3nCi/mL at 18 hours. Cumulative urinary excretion was ≤6% in 2.3 half-lives. The maximum external exposure rate immediately post-infusion at skin contact over the abdomen averaged 7.67 mR/h and dropped to 0.67 mR/h by 24 hours. The exposure rates at the other positions monitored (axilla, chest, and femur) decreased as a function of distance from the abdomen. The data points correlate closely with ²¹²Pb physical decay (T_1/2=10.6 hours). Follow-up >6 months showed no evidence of agent-related toxicity.

Conclusions: Pharmacokinetics and imaging after 0.2 mCi/m² IP ²¹²Pb-TCMC-trastuzumab in patients with HER-2-expressing malignancy showed minimal distribution outside the peritoneal cavity, ≤6% urinary excretion, and good tolerance.

 

Risk Perception, Worry, and Test Acceptance in Average-Risk Women Undergoing Ovarian Cancer Screening

abstract

Purchase $35.95

---

Objective

We evaluated baseline knowledge of ovarian cancer risk and perceptions toward ovarian cancer screening (OCS) in women initiating the normal risk ovarian screening study (NROSS).

Study Design

Average-risk, postmenopausal women were enrolled between 2001 and 2011 as they entered the NROSS. Participants completed baseline surveys of risk perception, cancer worry (Cancer Worry Scale), anxiety (State-Trait Anxiety Inventory), health and well-being (SF-36), and acceptability of OCS.

Results

Of the 1242 women enrolled, 925 (74.5%) completed surveys. The respondents estimated a mean lifetime risk of ovarian cancer of 29.9%, much higher than the actual risk of 1.4% for women in the U.S. Only 2.8% of participants correctly estimated their risk, while 35.4% reported their lifetime risk to be ≥50%. Cancer worry was low, with a median CWS score of 7 out of 24. Anxiety was comparable to published norms for women in this age group, with median STAI-S and STAI-T scores of 30 and 29 out of 80, respectively. Overall, women reported good physical and mental well-being. In terms of OCS acceptability, 97.2% of respondents agreed, or strongly agreed, that “the benefits of screening outweigh the difficulties.” Very few women were reluctant to undergo OCS due to time constraints (1.1%), pain (2.0%), or embarrassment (1.9%).

Conclusions

Average-risk women undergoing OCS highly overestimated their risk of ovarian cancer. Despite this, participants reported low cancer worry and anxiety. The discrepancy between knowledge of and attitudes toward ovarian cancer risk highlights the need for educational efforts in this area.

---

Funding Source: This study was supported by funds from the MD Anderson SPORE in Ovarian Cancer NCI P50 CA83639 and Grant Number T32 CA101642 from the NIH National Research Service Award. Dr. Skates was supported in part by grant CA152990 from NCI's Early Detection Research Network. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCI or NIH.

Presentation Information: This research was presented as a poster at the Society of Gynecologic Oncologists 43^rd Annual Meeting on Women’s Cancer in Austin, TX from March 24 – 27, 2012.

 

Clinician characteristics, communication, and patient outcome in oncology: a systematic review - De Vries - 2013 - Psycho-Oncology - Wiley Online Library

abstract
 

Objective

The aim of this study was to review the literature on clinician characteristics influencing patient–clinician communication or patient outcome in oncology.

Methods

Studies investigating the association of clinician characteristics with quality of communication and with outcome for adult cancer patients were systematically searched in MEDLINE, PSYINFO, PUBMED, EMBASE, CINHAL, Web of Science and The Cochrane Library up to November 2012. We used the preferred reporting items for systematic reviews and meta-analyses statement to guide our review. Articles were extracted independently by two of the authors using predefined criteria.

Results

Twenty seven articles met the inclusion criteria. Clinician characteristics included a variety of sociodemographic, relational, and personal characteristics. A positive impact on quality of communication and/or patient outcome was reported for communication skills training, an external locus of control, empathy, a socioemotional approach, shared decision-making style, higher anxiety, and defensiveness. A negative impact was reported for increased level of fatigue and burnout and expression of worry. Professional experience of clinicians was not related to communication and/or to patient outcome, and divergent results were reported for clinician gender, age, stress, posture, and confidence or self-efficacy.

Conclusions

Various clinician characteristics have different effects on quality of communication and/or patient outcome. Research is needed to investigate the pathways leading to effective communication between clinicians and patients. 

How Cancers Grow [Video]: Scientific American

Video

Metastatic Behavior of Upper Tract Urothelial Carcinoma After Radical Nephroureterectomy: Association with Primary Tumor Location

 Blogger's Note: this abstract does not indicate if Lynch Syndrome patients were included; of interest, especially, in light of the scarcity of research specific to UTUC (of the ureter/renal pelvis)

abstract

PURPOSE:

To investigate the site-specific pattern of disease recurrence and/or metastasis and the associated patient outcomes after radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC).

METHODS:

A total of 733 patients with UTUC from a retrospective multi-institutional cohort were included, with a median follow-up of 34 months. Associated patient outcomes were analyzed by multivariate analysis. To evaluate the influence of primary tumor location, we divided it into four areas: renal pelvis, and upper, middle, and lower ureter.

RESULTS:

A total of 218 patients experienced disease recurrence, with the majority of relapses occurring within the first 3 years. Cumulative incidence rates of first disease recurrence at 1 and 3 years were 18.9 and 29.8 %, respectively. Of these patients, 38.5 % developed distant recurrence; 17.4 % experienced both local and distant recurrences; and 44.0 % developed isolated local recurrence. The predominant sites of distant metastasis were lung, liver, and bone. Multivariate analysis revealed that the prevalence of local recurrence and lung metastasis was significantly associated, with primary tumor location being independent of other clinicopathological variables. Lower/middle ureter tumors had a higher rate of local recurrence in the pelvic cavity, and renal pelvic tumors had a higher prevalence of distant relapse in the lungs. Similar results were obtained when rerunning the data set by excluding patients who received adjuvant chemotherapy (n = 131).

CONCLUSIONS:

This multi-institutional study provided a detailed picture of metastatic behavior after RNU, and primary tumor locations were associated with unique patterns of metastatic spread in UTUC patients.

 

Research findings call for a rethinking of cancer genetics

rethinking 

"....Hardwick says the findings call researchers to greater scrutiny in their genetic analyses because they could unwittingly attribute a phenomenon to a gene they mutated, when it is actually due to a secondary mutation..... 

Vaccine Therapy and IDO1 Inhibitor INCB024360 in Treating Patients With Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Are in Remission

Full Text View 

This study is not yet open for participant recruitment.

Verified November 2013 by Roswell Park Cancer Institute

Sponsor:

Roswell Park Cancer Institute

Collaborator:

National Cancer Institute (NCI)

Information provided by (Responsible Party):

Roswell Park Cancer Institute

ClinicalTrials.gov Identifier:

NCT01982487

First received: November 6, 2013

Last updated: NA

Last verified: November 2013

History: No changes posted

 

A Registry for BRCA Mutation Carriers With Pancreatic Ductal Adenocarcinoma

Full Text View

ClinicalTrials.gov Identifier:

NCT01983410

First received: November 4, 2013

Last updated: November 7, 2013

Last verified: November 2013

 

Editorial: Ups and downs of evidence and practice guidelines (plus commentaries Yes/No)

 
Ups and downs

"...With evidence that does not stand the test of time and practice guidelines rife with expert opinions, it’s no wonder that family physicians no longer know what to believe!"

• Is evidence-based medicine overrated in family medicine?: Yes.

  Can Fam Physician November 2013 59: 1160-1161
  • Full Text
  • Full Text (PDF)

• Is evidence-based medicine overrated in family medicine?: No. 

  Can Fam Physician November 2013 59: 1162-1163

  • Full Text
  • Full Text (PDF)

  
  

  • Rebuttal: Is evidence-based medicine overrated in family medicine?: Yes.

    Can Fam Physician November 2013 59: e475
    • Full Text
    • Full Text (PDF)

  • Rebuttal: Is evidence-based medicine overrated in family medicine?: No.

    Can Fam Physician November 2013 59: e476
    • Full Text
    • Full Text (PDF)