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Sunday, September 28, 2014

open access: Assessment of adnexal masses using ultrasound: a practical review



 IJWH


Published Date September 2014 Volume 2014:6 Pages 857—863
DOI http://dx.doi.org/10.2147/IJWH.S47075
Received 7 May 2014, Accepted 15 July 2014, Published 23 September 2014
Noam Smorgick, Ron Maymon

Department of Obstetrics and Gynecology, Assaf HaRofeh Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

Abstract: Pelvic ultrasound is commonly used as part of the routine gynecologic exams, resulting in diagnosis of adnexal masses, the majority of which are functional or benign. However, due to the possible complications involving benign adnexal cysts (ie, adnexal torsion, pelvic pain) and the utmost importance of early diagnosis and treatment of ovarian cancer, the correct ultrasound diagnosis of adnexal masses is essential in clinical practice. This review will describe the typical ultrasound appearance of the common physiologic, benign, and malignant adnexal masses with the aim of aiding the clinician to reach the correct diagnosis.


Download Article [PDF]   

Wednesday, August 20, 2014

2014 Guidelines on genetic evaluation and management of Lynch syndrome: A consensus statement by the U.S. Multi-Society Task Force on Colorectal Cancer



open access


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What do patients and carers WANT from health apps? Survey (closes Fri, 24th Oct 2014)



Note: survey includes many options for country locations

Survey


 
 

INTRODUCTION TO THIS INDEPENDENT STUDY

Thank you for your interest in participating in this short online survey, “What do patients and carers WANT from health apps?”

The survey is being conducted by PatientView in collaboration with Health 2.0, with the input of relevant healthcare stakeholders (policy-makers, suppliers of apps and mobile services, and healthcare professionals).

The results of the survey will be made public on November 10th-11th 2014 at the Health 2.0 conference in London, which attracts about 500 delegates. The 2014 conference is focusing on engaging the entrepreneurs who are behind the development of health apps.

So, the results of this survey should go some way to providing valuable information to app developers about how to improve their apps to meet your needs.

ABOUT THE SURVEY
The survey is open to anybody who is living with an illness or condition that lasts many years (or even a lifetime), and is also open to the carers of people living with an illness or condition that lasts many years (or even a lifetime).

The survey is COMPLETELY ANONYMOUS AND CONFIDENTIAL.

The survey is short, with only 10 main questions, and should probably take no more than 10-15 minutes of your time.

As a survey participant, you can have a copy of the results emailed to you if you wish.

When this study will close
The study will close on Friday, 24th October 2014.

If you have any questions about this study, please contact ...
Dr Alexandra Wyke of PatientView
Tel: ++44-(0)1547-520-965
E-mail: info@patient-view.com


WHAT ARE 'HEALTH APPS'?
Health apps are software (computer programs) that can be downloaded onto smartphones or tablets, or, in some cases, accessed through the Web browser on your computer. Health apps aim to help people improve their health in various ways—for instance, by boosting their ability and motivation to exercise; by helping them manage their diet, or eat healthier foods; by providing them with a log to record their symptoms, blood pressure, diet, etc, for their doctor; by offering them information about their condition, etc.


Please continue with the survey by clicking NEXT >>



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The Histomorphology of Lynch Syndrome–associated Ovarian Carcinomas: Toward a Subtype-specific Screening Strategy



Abstract

Women with Lynch syndrome (LS) are at increased risk for the development of epithelial ovarian cancer (OC). Analogous to previous studies on BRCA1/2 mutation carriers, there is evidence to suggest a histotype-specific association in LS-associated OCs (LS-OC). Whereas the diagnosis of high-grade serous carcinoma is an indication for BRCA1/2 germline testing, in contrast, there are no screening guidelines in place for triaging OC patients for LS testing based on histotype. We performed a centralized pathology review of tumor subtype on 20 germline mutation-confirmed LS-OCs, on the basis of morphologic assessment of hematoxylin and eosin–stained slides, with confirmation by immunohistochemistry when necessary. Results from mismatch-repair immunohistochemistry (MMR-IHC) and microsatellite instability (MSI) phenotype status were documented, and detailed pedigrees were analyzed to determine whether previously proposed clinical criteria would have selected these patients for genetic testing. Review of pathology revealed all LS-OCs to be either pure endometrioid carcinoma (14 cases), mixed carcinoma with an endometrioid component (4 cases), or clear cell carcinoma (2 cases). No high-grade or low-grade serous carcinomas or mucinous carcinomas of intestinal type were identified. Tumor-infiltrating lymphocytes were prominent (≥40 per 10 high-powered fields) in 2 cases only. With the exception of 1 case, all tumors tested for MMR-IHC or MSI had an MMR-deficient phenotype. Within this cohort, 50%, 55%, 65%, and 85% of patients would have been selected for genetic workup by Amsterdam II, revised Bethesda Guidelines, SGO 10% to 25%, and SGO 5% to 10% criteria, respectively, with <60% of index or sentinel cases detected by any of these schemas. To further support a subtype-driven screening strategy, MMR-IHC reflex testing was performed on all consecutive non-serous OCs diagnosed at 1 academic hospital over a 2-year period; MMR deficiency was identified in 10/48 (21%) cases, all with endometrioid or clear cell histology. We conclude that there is a strong association between endometrioid and clear cell ovarian carcinomas and hereditary predisposition due to MMR gene mutation. These findings have implications for the role of tumor subtype in screening patients with OC for further genetic testing and support reflex MMR-IHC and/or MSI testing for newly diagnosed cases of endometrioid or clear cell ovarian carcinoma."

Commentary/Research: Obesity: a certain and avoidable cause of cancer - the Lancet



 Note: both open access; note strengths/weaknesses of study for clarity

Commentary: The Lancet

 The Study (the Lancet)  Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults



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Wednesday, August 06, 2014

Cancer biomarkers: Written in blood : Nature News



full text

 DNA circulating in the bloodstream could guide cancer treatment — if researchers can work out how best to use it.

Tuesday, August 05, 2014

The electronic self report assessment and intervention for cancer: promoting patient verbal reporting of symptom and quality of life issues in a randomized controlled trial



Full text 

Conclusions

Adding electronically-delivered, self-care instructions and communication coaching to ESRA-C promoted specific patient descriptions of problematic SxQOL issues compared with ESRA-C assessment alone. However, clinician verbal responses were no different and subsequent symptom distress group differences were not mediated by the patients' reports 

case report/review: A late, solitary brain metastasis of epithelial ovarian carcinoma



 Full text 

Wednesday, November 20, 2013

Dying at home – is it better: A narrative appraisal of the state of the science



abstract

Background: Achieving home care and home death is increasingly used as an outcome measure of palliative care services. 

Aim: To appraise the state of the science on dying at home. 

Methods: Appraisal and narrative review developed from a plenary presentation at the European Association for Palliative Care (EAPC) 2012 meeting examining the research on variations and trends in place of death, factors associated with dying in the preferred place, presenting evidence on outcomes for those dying at home and suggesting future research questions. 

Results: Meeting patients’ preferences and creating home-like environments has been a major concern for hospice and palliative care since its inception. During the 20th century, in many countries, hospital deaths increased and home deaths reduced. Despite the fact that this trend has been halted or reversed in some countries (notably the United States, Canada and, more recently, the United Kingdom) in the last 5–20 years, a home death is still a distant reality for the majority, even though evidence shows it is the most commonly preferred place to die. Epidemiological studies identified factors associated with home death, including affluence, patients’ preferences, provision of home care and extended family support. Evidence about the benefits of home care is conflicting, but recent data suggest that holistic well-being may be greater at home. 

Implications: We call for further analyses of variations in place of care and place of death and robust studies on how patients and families formulate and change preferences over time. Regular monitoring of outcomes, quality and costs of palliative home care is urged.
 

Psychological distress in women with breast and gynecological cancer treated with radical surgery



abstract

Objectives

The objective of this study is to compare psychological distress (body image disturbance, self-esteem, depression, and anxiety) in women with breast or gynecological cancer treated by radical surgery. Additionally, another objective is to analyze the association between psychological distress and sociodemographic characteristics, medical history, and social support to produce a prediction model for the outcome measures.

Methods

A cross-sectional study was carried out with 100 women who had undergone radical surgery for breast or gynecological cancer. Both groups were divided into the following: younger than 50 years old and 50 years old or older. Body Image Scale, Rosenberg's Self-Esteem Scale, Beck Depression Inventory, and Beck Anxiety Inventory were used.

Results

Age had a significant main effect on psychological distress but the type of cancer did not. Younger women showed significantly greater distress than older women (p-values < 0.001). A significant interaction between age and type of cancer was found, indicating that older women with breast cancer had worse body image and more depression than those with gynecological cancer (p-values < 0.001); no significant differences were found between younger groups.
The prediction model for increased body image disturbance and depression included the joint effect of the following variables: being younger, inactive occupational status, and post-adjuvant therapy side effects. For lower self-esteem, the variables were: being younger, post-adjuvant therapy side effects, and dissatisfaction with social support. And for higher anxiety, the sole variable included was post-adjuvant therapy side effects.

Conclusions

Both mastectomy and hysterectomy/oophorectomy cause similar psychological distress in younger women, but mastectomy causes greater distress in older women than hysterectomy/oophorectomy.

 

Twenty tips for interpreting scientific claims



Nature News & Comment

Debulking Surgery and Intraperitoneal Chemotherapy Are Associated With Decreased Morbidity in Women Receiving Neoadjuvant Chemotherapy for Ovarian Cancer



abstract

Objective: The aims of this study were to compare the rate of completion of optimal debulking and/or 6 cycles of intraperitoneal (IP) chemotherapy in women with International Federation of Gynecologists and Obstetricians stage III/IV ovarian cancer undergoing neoadjuvant chemotherapy (NACT) versus primary surgery (PS) and to compare morbidity between these 2 groups.

Methods: Ninety-six subjects with stage III/IV ovarian cancer who underwent either NACT or PS were identified. Data comparisons include rate of optimal debulking and completion rate of 6 cycles of IP chemotherapy. Other data collected included surgical times, length of stay, intensive care unit admissions, blood transfusions, bowel resections, major complications, and dose reductions. SigmaStat version 2.0 was used for statistical analysis.

Results: Of the 96 subjects, 38 received NACT and 58 had PS. All 14 subjects with stage IV disease received NACT, and all experienced resolution of pleural effusion, based on computed tomographic imaging. Thirty-five (92%) of 38 NACT subjects versus 47 (81%) of 58 PS subjects were optimally debulked (P = 0.08). Thirty-six (95%) of 38 NACT subjects versus 37 (64%) of 58 PS subjects completed IP chemotherapy (P < 0.001). Length of stay was 3.26 (NACT) versus 5.08 (PS) days (P < 0.001). Intensive care unit admissions were 1 of 38 (NACT) versus 12 of 58 (PS) (P < 0.001). Bowel resections were done in 2 of 38 (NACT) versus 14 of 38 (PS) (P < 0.05). Duration of surgery was 96 minutes (NACT) versus 138 minutes (PS) (P < 0.001). A trend to fewer dose reductions occurred in NACT (1/38) versus PS (8/58) (P = 0.056).

Conclusions: The NACT subjects were more likely to complete IP chemotherapy and had decreased length of stay, intensive care unit admissions, bowel resections, and duration of surgery. Both optimal debulking and dose reductions were numerically but not statistically associated with NACT versus PS. This likely reflects a relatively high overall rate of optimal debulking and low rate of dose reductions in these subjects and would require a larger group to determine significance.


 

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.
 

Tuesday, November 19, 2013

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.

 

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:
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 ushas 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.  

Monday, November 18, 2013

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

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).

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