OVARIAN CANCER and US

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Tuesday, April 10, 2012

Google search: "clear cell ovarian"




JCO search: "clear cell ovarian"



Blogger's Note: these search results are not entirely specific but date back to 1987

 JCO - Searching journal content for clear cell ovarian (all words) in title or abstract.

Displaying results 1-60 of 93

a must! JCO Podcast - Commentary: Low-Stage Ovarian Clear Cell Carcinoma: Population-Based Outcomes in British Columbia, Canada, With Evidence for a Survival Benefit As a Result of Irradiation



 Blogger's Opinion/Notes:

  •  it is very worthwhile to listen to this podcast 
  • radiation therapy in ovarian cancer has a very long history and in particular biases 
  •  this podcast is a stunningly frank observation regarding clear cell ovarian cancer/radiation therapy, observation/s on the recent Hoskins clear cell report  including the issues of size of studies eg. clear cell ovarian cancer (in particular) has a low incidence rate and therefore, agreeably (mine) that this is a point/statistic which cannot be changed eg. rare cell types
  •  this blog has many past posts over decades of research regarding radiation/irridation therapy in clear cell/ovarian cancer
  • a blog/or otherwise search on this issue would be wise to understand the points being made in these two articles
  • note also the Hoskins abstract regarding survival rates in clear cell ovarian cancer which, IMHO, have been widely ignored (stats issues) for decades (eg. early stage survival rates ~90% - popular stats quotes)

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

JCO Podcast

Low-Stage Ovarian Clear Cell Carcinoma: Population-Based Outcomes in British Columbia, Canada, With Evidence for a Survival Benefit As a Result of Irradiation 


Users can play the podcast directly in the audio player embedded below. If Flash is disabled on your browser, you can save the file directly to your computer or open on your mobile device by clicking on "download file."

Management of Low Stage Ovarian Clear Cell Carcinoma
by Martin Gore


(Download file - duration 0:08:22, file size 7.69 MB)

abstract: Low-Stage Ovarian Clear Cell Carcinoma: Population-Based Outcomes in British Columbia, Canada, With Evidence for a Survival Benefit As a Result of Irradiation



Low-Stage Ovarian Clear Cell Carcinoma: Population-Based Outcomes in British Columbia, Canada, With Evidence for a Survival Benefit As a Result of Irradiation

 Abstract

Purpose 
To evaluate the population-based outcomes of stage I and II ovarian clear cell carcinoma (OCCC) in a North American population treated with carboplatin/paclitaxel and abdominopelvic irradiation.

Patients and Methods 
Retrospective analysis was performed of 241 patients referred in the carboplatin/paclitaxel era. Irradiation was to be used with a few defined exceptions. However, because of differing beliefs as to its effectiveness, its use was consistently avoided by specific oncologists, allowing the opportunity to study its possible effect on disease-free survival (DFS) in these concurrent cohorts. 

Results 
Five- and 10-year DFS rates were 84% and 70% for stage IA/B; 67% and 57% for stage IC; and 49% and 44% for stage II, respectively. 

Five- and 10-year DFS rates for those with stage IC disease based purely on rupture were similar to rates for patients with stage IA/B, at 92% and 71%, respectively

The remaining patients with stage IC had 48% 5- and 10-year DFS. 

 Multivariate analysis using a decision tree identified positive cytology as the most important factor (72% relapse rate if positive and 27% if negative or unknown). 

If, in addition, the capsule surface was involved, then the relapse rate was 93%. Irradiation had no discernible survival benefit for patients with stage IA and IC (rupture alone), whereas for the remainder of patients with stage IC and stage II, it improved DFS by 20% at 5 years (relative risk, 0.5); the benefit was most evident in the cytologically negative/unknown group. 

Conclusion 
DFS is similar in this North American population with early OCCC to the DFS reported in Asia. A potential benefit from irradiation was evident in a subset.

Monday, April 09, 2012

The Drug Shortage Wars | The Health Care Blog (ovarian cancer untreated for weeks)



The Drug Shortage Wars | The Health Care Blog


“I should have gotten cancer last month,” she told me.

That was the first thought from my patient after she’d heard the news: her ovarian cancer would remain untreated for weeks, due to a critical shortage of the chemotherapy agent doxorubicin. Like her, several thousand patients have been affected by critical shortages of chemotherapy agents like doxorubicin (Doxil) and methotrexate—common medicines that are essential backbones of cancer chemotherapy. But hundreds of other people have also been affected by critical shortages of pills around the country—limiting the supply of critical ICU medications like intravenous versed, or tuberculosis drugs like isoniazid.
Why are these shortages happening, and what can be done about them?....

 Related Posts

worth reading: Lessons for journalists & the public about medical conference news



 Blogger's Note: this is worth reading mostly in particular to the reading of published abstracts and the ultimate findings/abstract accuracy

 

Lessons for journalists & the public about medical conference news

Abstract - Biotargets of Cancer in Current Clinical Practice - Ovarian Cancer



 Medicine
Current Clinical Pathology, 2012, 381-401, DOI: 10.1007/978-1-61779-615-9_14

Abstract -
  
Abstract
Ovarian cancer is the fifth most common cancer in women and is the most lethal of all gynecologic cancers. Early-stage ovarian cancer is curable while women who are diagnosed with advanced ovarian cancer continue to have poor long-term survival due to recurrence of disease. Unfortunately, most women are diagnosed with advanced-stage disease. Early detection is a primary objective for clinicians and scientists, yet single modality (CA-125, transvaginal ultrasound) screening tests have been ineffective. More recent novel approaches combining modalities and utilizing serial serum sampling are being tested and hold great promise. In addition, the recent application of proteomics to this clinical question has the potential to identify new and important biotargets.
Unfortunately, the majority of ovarian cancer patients have advanced-stage disease, and although most will die of their disease, their survival is quite heterogenous (different). 
The ability to stratify patients according to prognosis could help guide therapy. The current “gold standard” for prognosis uses patient, surgical, and tumor characteristics, yet these have the tendency to be notoriously inaccurate. This prognostic uncertainty and the drive to identify predictive factors by which we can select novel and targeted therapy have stimulated researchers to look beyond traditional markers and test and validate molecular and genomic biomarkers, which are anticipated to soon complement or even eclipse traditional factors clarifying prognosis and select treatments. 
For patients with advanced-stage disease, a multitude of prognostic factors have been characterized. While promising, none of these biotargets have been validated at present to be clinically useful. More recent application of genomic technologies is likely to yield clinically relevant signatures and/or biotargets which will provide the basis for personalization of care for these patients.

Cochrane Review: abstract/plain text summary - Centralisation of services for gynaecological cancer - The Cochrane Library - Woo - Wiley Online Library



Centralisation of services for gynaecological cancer - The Cochrane Library 

Authors' conclusions

We found low quality, but consistent evidence to suggest that women with gynaecological cancer who received treatment in specialised centres had longer survival than those managed elsewhere. The evidence was stronger for ovarian cancer than for other gynaecological cancers.
Further studies of survival are needed, with more robust designs than retrospective observational studies. Research should also assess the quality of life associated with centralisation of gynaecological cancer care. Most of the available evidence addresses ovarian cancer in developed countries; future studies should be extended to other gynaecological cancers within different healthcare systems.
 

Plain language summary

Gynaecological cancers are cancers affecting the ovaries, uterus, cervix, vulva, and vagina.  They are the second most common cancers among women, after breast cancer. It is often suggested that outcomes are improved by centralising care within highly specialised services that include expert surgeons, radiologists, pathologists, oncologists who specialise in chemotherapy and radiotherapy, specialist nurses and other health professionals. However, consensus is lacking on whether centralisation of care for gynaecological cancer helps patients to live longer. This review investigated this issue by comparing the survival of women diagnosed with gynaecological cancer who received care from specialised and unspecialised centres.

We used a set of tests to ensure that the evidence the five studies identified reached the quality standard for our analysis.The analysis of three studies combined (meta-analysis), assessing over 9000 women, suggested that institutions with gynaecologic oncologists (specialists in the field of gynaecological cancer treatment) on site may prolong the lives of women with ovarian cancer compared to community or general hospitals. Similarly, another meta-analysis of three studies which assessed well over 50,000 women, found evidence to suggest that teaching centres or regional cancer centres (specialised centres) (Blogger's Note: do the specialized/regional centre have gynecologic oncologists/clinical trial access....) may prolong the lives of women with gynaecological cancer compared to community or general hospitals. The largest study in this meta-analysis assessed all gynaecological cancers in 48,981 women, so it had major influence on the final result; this means that our findings are likely to be relevant to other gynaecological cancers, besides ovarian cancer.

Overall, the findings suggest that centralisation of care may prolong the lives of women with gynaecological cancer, and in particular ovarian cancer. However, the results should be interpreted with caution as all of the studies included in the review could be biased. For example, it is possible that the patients who were treated in specialised centres were less ill to begin with. Another weakness of the review is that only one of the studies included women with gynaecological cancers other than ovarian cancer. (Blogger's opinion: any studies of this nature should differentiate and isolate/categorize the gynecologic cancers as treatments, side effects, survival rates, genetics....vary greatly)

Ideally, further studies in this area are needed.  New studies should be designed to avoid the possibility of bias due to the treatment of women at specialist and non-specialist centres being systematically different.

Additionally, studies should assess the impact of centralisation of care on the quality of life of patients.

Most of the available evidence was about ovarian cancer in developed countries; future studies should be extended to other gynaecological cancers and to less developed countries.

Ontario (Canada) ombudsman could hold hospitals to account - thestar.com



Ontario ombudsman could hold hospitals to account - thestar.com

"Ontario is also the only province whose ombudsman cannot investigate hospitals and long-term care facilities."

abstract: Multidrug Resistance-Linked Gene Signature Predicts Overall Survival of Patients With Primary Ovarian Serous Carcinoma



Multidrug Resistance-Linked Gene Signature Predicts Overall Survival of Patients With Primary Ovarian Serous Carcinoma

Abstract

Purpose: 
This study assesses the ability of multidrug resistance (MDR)-associated gene expression patterns to predict survival in patients with newly diagnosed carcinoma of the ovary. The scope of this research differs substantially from that of previous reports, as a very large set of genes was evaluated whose expression has been shown to affect response to chemotherapy. 

Experimental Design: 
We applied a customized TaqMan Low Density Array, a highly sensitive and specific assay, to study the expression profiles of 380 MDR-linked genes in 80 tumor specimens collected at initial surgery to debulk primary serous carcinoma. The RNA expression profiles of these drug resistance genes were correlated with clinical outcomes. 

Results: 
Leave-one-out cross-validation was used to estimate the ability of MDR gene expression to predict survival. Although gene expression alone does not predict overall survival (P=0.06), four covariates (age, stage, CA125 level and surgical debulking) do (P=0.03). 
When gene expression was added to the covariates, we found an 11-gene signature that provides a major improvement in overall survival prediction (log-rank statistic P less than 0.003). The predictive power of this 11-gene signature was confirmed by dividing high and low risk patient groups, as defined by their clinical covariates, into four specific risk groups based on expression levels. 

Conclusion: 
This study reveals an 11-gene signature that allows a more precise prognosis for patients with serous cancer of the ovary treated with carboplatin- and paclitaxel-based therapy. These 11 new targets offer opportunities for new therapies to improve clinical outcome in ovarian cancer.

abstract: Adnexal masses in women with breast cancer



Adnexal masses in women with breast cancer:

Background

Adnexal masses detected in breast cancer survivors are of particular concern because of the increased risk of ovarian malignancy.

Aims

This study was performed to analyse adnexal masses among women with breast cancer with regard to variables predictive of malignancy.

Methods

The study included women with breast cancer who had undergone surgery for an adnexal mass between 2002 and 2010 at Hacettepe University Hospital. A total of 45 consecutive women with a mean age of 47.3 years (range 25–76) were analysed retrospectively.

Results

Of 45 cases reviewed, benign ovarian pathology was found in 35 cases (77.8%) and malignant ovarian neoplasms were found in 10 cases (22.2%). A simple ovarian cyst was observed in 25 cases (71.4%) as the most common type of benign pathology. Of the 10 cases with malignancy, 5 (50%) had primary ovarian carcinoma, while the remaining five women had breast carcinoma metastases to the ovary. Complex mass at ultrasonography, increased CA 125 level and oestrogen receptor–negative tumour were found to be the significant predictors of ovarian malignancy.

Conclusions

Although an adnexal mass in a woman with breast cancer is most commonly a benign ovarian cyst, the overall risk of ovarian malignancy is increased with breast cancer. An adnexal mass with complex architecture detected by ultrasonography and high CA 125 level were the strongest risk factors associated with increased risk of malignancy.

Optimizing Molecular-Targeted Therapies in Ovarian Cancer: The Renewed Surge of Interest in Ovarian Cancer Biomarkers and Cell Signaling Pathways : Table 1 (eg. HE4....)



Blogger's Note: the table includes biomarkers for ovarian cancer in research

Optimizing Molecular-Targeted Therapies in Ovarian Cancer: The Renewed Surge of Interest in Ovarian Cancer Biomarkers and Cell Signaling Pathways : Table 1

original article previously posted - link:
Journal of Oncology


abstract: Psychiatric morbidity in gynecological outpatients



Psychiatric morbidity in gynecological outpatients - Judd - 2012 - Journal of Obstetrics and Gynaecology Research

Abstract

Aim:  To assess the prevalence of depression and anxiety in women presenting with gynecological symptoms, to determine how many women with these disorders were receiving treatment for them, and to investigate risk factors for these disorders.
Method:  Two hundred and sixty-four women seeking medical care from gynecology clinics at a specialist women's hospital completed a self-report questionnaire asking about sociodemographics, physical and mental health, personality (neuroticism) and psychosocial stressors.
Results:  A total of 91 women met the diagnostic criteria for one or more Patient Health Questionnaire (PHQ) diagnosis. Forty-six (17.4%) met criteria for major depressive disorder (MDD), 15 (5.7%) for panic disorder (PD) and 73 (27.7%) for generalized anxiety disorder (GAD). Thirty-nine (42.9%) of the 91 women met criteria for two or more disorders. An additional 23 (8.7%) met DSM-IV-TR criteria for minor (sub-threshold) depression. Fifty percent with MDD, 4% with minor depression, 53% with PD and 22% with GAD reported they were receiving treatment. Psychosocial stressors and the neuroticism score were risk factors for both anxiety and depression.
Conclusions:  Anxiety and depression are common amongst women attending a gynecology clinic. Clinicians should be alert to the possibility of these disorders and make specific enquiries about their emotional wellbeing.

The Medicare NewsGroup introduces new website for journalists



The Medicare NewsGroup introduces new website for journalists

abstract: Evaluation of 2-Deoxy-2-[18F]Fluoro-D-glucose- and 3′-Deoxy-3′-[18F]Fluorothymidine–Positron Emission Tomography as Biomarkers of Therapy Response in Platinum-Resistant Ovarian Cancer



Molecular Imaging and Biology, Online First™ 

Abstract


Purpose  

We evaluated whether 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) and 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) positron emission tomography (PET) could be used as imaging biomarkers of platinum resensitization in ovarian cancer.

Procedures  

Paired platinum-sensitive and platinum-resistant ovarian cancer cells from the same patient, PEO1 and PEO4, grown as tumor xenografts in nude mice, were assessed by PET.

Results  

The AKT inhibitor, API-2, resensitized platinum-resistant PEO4 tumors to cisplatin, leading to a markedly lower Ki67 labeling index (p ≤ 0.006, n = 6 per group). [18F]FDG-PET and [18F]FLT-PET imaging variables were lower after combination treatment compared with vehicle treatment (p ≤ 0.006, n = 6 per group). No changes were seen with either drug alone. PRAS40 phosphorylation status was a sensitive biochemical marker of pathway inhibition, whereas reductions thymidine kinase 1 expression defined the [18F]FLT response.

Conclusions  

Therapeutic inhibition of AKT activation in acquired platinum-resistant disease can be imaged noninvasively by [18F]FDG-PET and [18F]FLT-PET warranting further assessment. 

Seth's Blog: Is everyone entitled to their opinion?



Seth's Blog: Is everyone entitled to their opinion?

Is everyone entitled to their opinion?

Perhaps, but that doesn't mean we need to pay the slightest bit of attention.

There are two things that disqualify someone from being listened to:

1. Lack of Standing. If you are not a customer, a stakeholder or someone with significant leverage in spreading the word, we will ignore you. And we should.
When you walk up to an artist and tell her you don't like her painting style, you should probably be ignored. If you've never purchased expensive original art, don't own a gallery and don't write an influential column in ArtNews, then by all means, you must be ignored.
If you're working in Accounts Payable and you hate the company's new logo, the people who created it should and must ignore your opinion. It just doesn't matter to anyone but you.
I'm being deliberately harsh here for a reason. If we're going to do great work, it means that some people aren't going to like it. And if the people who don't like it don't have an impact on what happens to the work after it's complete, the only recourse of someone doing great work is to ignore their opinion.

2. No Credibility. An opinion needs to be based on experience and expertise. I know you don't like cilantro, but whether or not you like it is not extensible to the population at large. On the other hand, if you have a track record of matching the taste sensibility of my target market, then I very much want to hear what you think.
People with a history of bad judgment, people who are quick to jump to conclusions or believe in unicorns or who have limited experience in the market--these people are entitled to opinions, but it's not clear that the creator of the work needs to hear them. They've disqualified themselves because the method they use for forming opinions about how the market will respond is suspect. The scientific method works, and if you're willing to suspend it at will and just go with your angry gut, we don't need to hear from you.

If these two standards sound like precisely the opposite of what gets you on talk radio or active in anonymous chat rooms, you're right. Running your business or your campaign or your non-profit or your sports team based on what you hear on talk radio is nuts.

Blogger's Opinion: repost (2011) : Proteomic biomarkers in combination with CA 125 for detection of epithelial ovarian cancer using prediagnostic serum samples from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial - Moore - 2011 - Cancer - Wiley Online Library



Blogger's Note/Opinion:  
efforts to improve on the existing CA125 biomarkers remain elusive, as we speak;  this may be confirmed by the multitude of research studies/meta-analsyes (known issues); we, as patients/survivors, all have examples which are contrary, or exceptions,  to what is presently known and therefore the issue of 'personalized medicine'; biomarker banking (tissues from surgery for research) is an important key element for those diagnosed so that we may move forward beyond the standard CA125 (as one example); on the bonus side - research is moving forward at a greatly accelerated pace (molecular/proteomics...) but the research is still in the phase/s of being brought to the 'clinic',  meaning what actually works for our ovarian cancer women pre-present-post diagnosis; it is a common philosophy in ovarian cancer research that due to our low numbers (relative to other cancers) that we must have global research (not least of which is to mention global economics); as patients you can make a difference by ensuring that the clinical studies which you enroll will make a difference in these efforts as opposed to small isolated studies - specifically those that continue to regurgitate past studies which do not move forward beyond the existing eg. psychosocial aspects of prophlactic surgery


Proteomic biomarkers in combination with CA 125 for detection of epithelial ovarian cancer using prediagnostic serum samples from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial - Moore - 2011 - Cancer

RESULTS (abstract):

"CA 125 levels were elevated (≥35 U/mL) in 61.5% of 65 patients who had CA 125 data available from samples that were collected <12 months before cancer diagnosis; however, levels of the additional 7 biomarkers were not different between cases and the 3 control groups individually or combined. Two panels that combined CA 125 and the 7 biomarkers failed to improve the sensitivity of CA 125 alone."

DISCUSSION

 ".....Although a marginally better performance was observed for the identification of cases at least 6 months before diagnosis using an all-site multimarker panel (which included CA 125, HE4, tumor-associated glycoprotein 72 [CA 72-4], substance P-like immunoreactivity, andβ2M) were observed compared with CA 125 alone, the increase was not statistically significant.21 In addition to the current study, 5 additional panels were evaluated, none of which improved on the results with CA 125 alone.8 Considering the failure of multiple biomarkers to improve upon CA 125 in prediagnostic samples, new approaches are badly needed for biomarker discovery. One weakness of the current study is that we were unable to evaluate markers in nonwhite populations because of a very small number of nonwhite cases in the PLCO trial. The results of this combined effort will likely reshape our approach to biomarker discovery and validation. In addition to searching for protein analytes, autoantibodies also may be sought. Finally, previous studies have had limited success in identifying and evaluated autoantibodies of human proteins expressed in bacteria or insect cells. Recent advances in expressing human proteins in human cells could allow the identification of new epitopes that are selective for altered tertiary structure and glycosylation status of selected protein targets."

Saturday, April 07, 2012

JNCI abstract: Tying Fallopian Tubes to Ovarian Cancer Risk



Blogger's Note: full access by subscription ($$$)

Tying Fallopian Tubes to Ovarian Cancer Risk

abstract - Gynecologic Oncology - Outcome of immediate re-operation or interval debulking after chemotherapy at a gynecologic oncology center after initially incomplete cytoreduction of advanced ovarian cancer



Gynecologic Oncology - Outcome of immediate re-operation or interval debulking after chemotherapy at a gynecologic oncology center after initially incomplete cytoreduction of advanced ovarian cancer


Background

Prognosis in advanced ovarian cancer is largely determined by completeness of tumor resection achieved during primary surgery. Incomplete initial debulking occurs frequently in non-specialized centers and there is an ongoing discussion about the best time for re-surgery after referral to tertiary centers.

Methods

Patients with advanced epithelial ovarian cancer (FIGO IIIB-IV) admitted between 1999 and 2007 who had primary incomplete surgery including those with initiated chemotherapy at outside institution were included. Surgical results, morbidity and prognosis were evaluated in patients with immediate re-operation before chemotherapy and those with interval debulking.

Results

48 eligible patients were identified in our tumor registry. Self-referral by patient was the most frequent mode of admission (n = 21, 43.8%). 22 patients (45.8%) patients underwent immediate re-surgery and 26 patients (54.2%) had an interval debulking after chemotherapy. In 12 patients (54.5%), macroscopically complete tumor removal could be achieved by immediate re-operation and in 17 patients (65.4%) after chemotherapy. Major complications were observed more frequently in patients with interval debulking (26.9 vs. 9.1%, p = 0.324). Median overall survival time was 53 and 34 months (p = 0.110) after immediate and delayed re-operation, respectively.

Conclusions

Upfront re-operation before start of chemotherapy is feasible and successful in an expertise referral centre in more than half of patients with incomplete primary surgery elsewhere. Complete resection even after initial incomplete debulking could improve outcome. Therefore, referral to expertise centers in those patients should be considered. Progression-free survival and overall survival showed a non-significant trend and complication rate a remarkable advantage in favor of upfront re-operation.

Keywords

  • primary ovarian cancer;
  • cytoreductive surgery;
  • interval debulking surgery

abstract: Cochrane Review: Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer



Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer [Cochrane Database Syst Rev. 2012] - PubMed - NCBI

Cochrane Database Syst Rev. 2012 Mar 14;3:CD004706.

Abstract

BACKGROUND:

Epithelial ovarian cancer is diagnosed in 4500 women in the UK each year of whom 1700 will ultimately die of their disease.Of all cases 10% to 15% are diagnosed early when there is still a good possibility of cure. The treatment of early stage disease involves surgery to remove disease often followed by chemotherapy. The largest clinical trials of this adjuvant therapy show an overall survival (OS) advantage with adjuvant platinum-based chemotherapy but the precise role of this treatment in subgroups of women with differing prognoses needs to be defined.

OBJECTIVES:

To systematically review the evidence for adjuvant chemotherapy in early stage epithelial ovarian cancer to determine firstly whether there is a survival advantage of this treatment over the policy of observation following surgery with chemotherapy reserved for treatment of disease recurrence, and secondly to determine if clinical subgroups of differing prognosis based on histological sub-type, or completeness of surgical staging, have more or less to gain from chemotherapy following initial surgery.

SEARCH METHODS:

We performed an electronic search using the Cochrane Gynaecological Cancer Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL 2011, Issue 3), MEDLINE (1948 to Aug week 5, 2011) and EMBASE (1980 to week 36, 2011). We developed the search strategy using free-text and medical subject headings (MESH).

SELECTION CRITERIA:

We selected randomised clinical trials that met the inclusion criteria set out based on the populations, interventions, comparisons and outcome measures.

DATA COLLECTION AND ANALYSIS:

Two review authors independently extracted data and assessed trial quality. Disagreements were resolved by discussion with a third review author. We performed random-effects meta-analyses and subgroup analyses.

MAIN RESULTS:

Five randomised controlled trials (RCTs), enrolling 1277 women, with a median follow-up of 46 to 121 months, met the inclusion criteria. Four trials were included in the meta-analyses and we considered them to be at a low risk of bias. Meta-analysis of five-year data from three trials indicated that women who received adjuvant platinum-based chemotherapy had better overall survival (OS) than those who did not (1008 women; hazard ratio (HR) 0.71; 95% confidence interval (CI) 0.53 to 0.93). Likewise, meta-analysis of five-year data from four trials indicated that women who received adjuvant chemotherapy had better progression-free survival (PFS) than those who did not (1170 women; HR 0.67; 95% CI 0.53 to 0.84). The trials included in these meta-analyses gave consistent estimates of the effects of chemotherapy. In addition, these findings were robust over time (10-year PFS: two trials, 925 women; HR 0.67; 95% CI 0.54 to 0.84).

Subgroup analysis suggested that women who had optimal surgical staging of their disease were unlikely to benefit from adjuvant chemotherapy (HR for OS 1.22; 95% CI 0.63 to 2.37; two trials, 234 women) whereas those who had sub-optimal staging did (HR for OS 0.63; 95% CI 0.46 to 0.85; two trials, 772 women).

One trial showed a benefit from adjuvant chemotherapy among women at high risk (HR for OS 0.48; 95% CI 0.32 to 0.72) but not among those at low/medium risk (HR for OS 0.95; 95% CI 0.54 to 1.66). However, these subgroup findings could be due to chance and should be interpreted with caution.

AUTHORS' CONCLUSIONS:

Adjuvant platinum-based chemotherapy is effective in prolonging the survival of the majority of patients who are assessed as having early (FIGO stage I/IIa) epithelial ovarian cancer. However, it may be withheld from women in whom there is well-differentiated encapsulated unilateral disease (stage 1a grade 1) or those with comprehensively staged Ib, well or moderately differentiated (grade 1/2) disease. 

Others with unstaged early disease or those with poorly differentiated tumours should be offered chemotherapy. A pragmatic approach may be necessary in clinical settings where optimal staging is not normally performed/achieved. In such settings, adjuvant chemotherapy may be withheld from those with encapsulated stage Ia grade 1 serous and endometrioid carcinoma and offered to all others with early stage disease.

Fulltext | Epithelial ovarian cancer: A feasible plan for adjunctive treatment using simultaneous acyclovir, ambrisentan, captopril, disulfiram, fluvoxamine-augmented ramelteon, icatibant, imiquimod peritoneal lavage, and plerixafor | Journal of Cancer Therapeutics & Research



Fulltext | Epithelial ovarian cancer: A feasible plan for adjunctive treatment using simultaneous acyclovir, ambrisentan, captopril, disulfiram, fluvoxamine-augmented ramelteon, icatibant, imiquimod peritoneal lavage, and plerixafor | Journal of Cancer Therapeutics & Research

Conclusion


To improve the prognosis in EOC an effort to comprehensively block growth factors that have been identified as active in human EOC as suggested in this paper may prove fruitful. Past research indicates that several already-approved and marketed drugs might do this. The nine drugs have no clearly discernable interaction with each other and none would be expected to interfere with concomitant current cytotoxic chemotherapy regimens although such cannot be excluded. Given the safety of the nine drugs individually, and the poor prognosis of an EOC seeded peritoneum, the risk of unexpected side effects or interaction I believe is worth taking.

abstract: Assumptions of Expected Benefits in Randomized Phase III Trials Evaluating Systemic Treatments for Cancer



Blogger's Note: also reference related commentary: " Why Do Phase III Clinical Trials in Oncology Fail so Often?


                 ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
Assumptions of Expected Benefits in Randomized Phase III Trials Evaluating Systemic Treatments for Cancer

open access: Why Do Phase III Clinical Trials in Oncology Fail so Often?



Why Do Phase III Clinical Trials in Oncology Fail so Often?

 "Achieving success in the development of a cancer drug continues to be challenging. Given the increasing costs (1) and the small number of drugs that gain regulatory approval (2), it is crucial to understand these failures. In this issue of the Journal, Gan et al. (3) reviewed 235 recently published phase III randomized clinical trials (RCTs). They report that 62% of the trials did not achieve results with statistical significance. Trying to explain the high failure rate, they note the actual magnitude of benefit achieved in a clinical trial (designated B) is nearly always less than what was predicted at the time the trial was designed (designated δ) and conclude, “investigators consistently make overly-optimistic assumptions regarding treatment benefits when designing RCTs.”
But really should we be surprised that phase III trials, the venue for detecting “small” differences, so often disappoint? Almost by definition, phase III studies are designed to detect small differences (4,5). The problem is that small has given way to “marginal” as outcomes have fallen below our already modest expectations. And who or what is to blame? Are investigators really overly optimistic regarding experimental therapies and, as the authors suggest, responsible for the large number of negative studies? Although we agree that optimism regarding clinical benefit may lead to an underpowered trial, we disagree that optimistic investigators are those we should blame. We would ask, how do Gan et al. (3) define optimism? Where do they place the line between an optimistic and a realistic expectation?.........

open access: online book - Ovarian cancer: the recognition and initial management of ovarian cancer - NICE





Ovarian cancer: the recognition and initialmanagement of ovarian cancer

This guidance updates and replaces recommendation 1.7.4 in
‘Referral guidelines for suspected cancer’ (NICE clinical guideline
27; published June 2005).

Full Guideline (148 pages)
April 2011

Developed for NICE by the National Collaborating Centre for Cancer
 Published by the National Collaborating Centre for Cancer (2nd Floor, Front Suite, Park House, Greyfriars Road, Cardiff,
CF10 3AF) at Velindre NHS Trust, Cardiff, Wales.
First published 2011
©2011 National Collaborating Centre for Cancer

Friday, April 06, 2012

JCO Special Series Overview Table of Contents — April 10, 2012



Table of Contents — April 10, 2012, 30 (11)

 Special Series Overview

Review Articles

open access: Caring for the Whole Patient: The Science of Psychosocial Care



Caring for the Whole Patient: The Science of Psychosocial Care

"This Journal of Clinical Oncology Special Series relates to the science of psychosocial care. This series is designed to provide oncology professionals with the most recent information about the psychological, psychiatric, and social aspects of cancer care.....

media: Cheap Diabetes Drug May Be Newest Weapon Against Cancer



Cheap Diabetes Drug May Be Newest Weapon Against Cancer

"Researchers warned there is still much work to be done before they can definitively say whether metformin can be used as a cancer drug."

abstract: Management of highly emetogenic chemotherapy



Management of highly emetogenic chemotherapy. [Curr Opin Oncol. 2012] - PubMed - NCBI

 Definition for emetogenic:

Web definitions:
Vomiting (known medically as emesis and informally as throwing up and a number of other terms) is the forceful expulsion of the contents...
en.wikipedia.org/wiki/Emetogenic

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

Abstract

PURPOSE OF REVIEW:

This review updates the clinical data on antiemetic therapy for chemotherapy classified as highly emetogenic.

RECENT FINDINGS:

A meta-analysis demonstrated that palonosetron was superior to other 5-hydroxytryptamine3 (5-HT3) receptor antagonists at least in the absence of aprepitant. Two major guideline groups have reclassified all chemotherapy that contains cyclophosphamide and an anthracycline as 'highly emetogenic'. Although recommended prophylaxis for drugs in that category includes aprepitant, phase II studies with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) and doxorubicin, bleomycin, vincristine and dacarbazine (ABVD) demonstrated that single agent palonosetron alone provided control of emesis over 85% of patients. A randomized phase III trial of olanzapine versus aprepitant found that the control of emesis was similar and nausea was significantly better controlled with olanzapine. Two studies showed that there is no impact of the moderate cytochrome P450 3A4 (CYP3A4) inhibitor aprepitant on the pharmacokinetics of cyclophosphamide. Surveys in the United States and Europe demonstrated that antiemetic prescribing practices often do not adhere to guidelines even for highly emetogenic chemotherapy.

SUMMARY:

The major guideline groups recommend a combination of a 5-HT3 receptor antagonist, dexamethasone and aprepitant ('triple therapy') for treatment categorized as highly emetogenic. Recent data suggest that, although classified as highly emetogenic, palonosetron may provide very good control of emesis for CHOP and ABVD.
Guidelines have not made firm recommendations for highly emetogenic chemotherapy administered over several days or stem cell transplant preparative regimens due to the lack of published randomized trials. Although well tolerated and effective, many patients receive suboptimal antiemetic therapy that includes aprepitant.

BRCA 1/2 Decision Tool - Stanford Medicine Cancer Institute



 Blogger's Note: variables can be changed eg. age/prophylactic surgery/s (type), easy to use, tip: hold your cursor over the chart to show %'s (outcomes)

BRCA Decision Tool

2011 Medical News ASCO: Abagovomab No Help in Ovarian Cancer - in Meeting Coverage, ASCO from MedPage Today



Medical News: ASCO: Abagovomab No Help in Ovarian Cancer - in Meeting Coverage, ASCO from MedPage Today


"Abagovomab maintenance treatment after debulking surgery and successful platinum and taxane first-line chemotherapy did not prolong progression-free survival in advanced ovarian cancer," he said in a late-breaker report given during a packed plenary session.

The invited discussant for the MIMOSA trial, George Coukos, MD, PhD, professor of gynecologic oncology at the University of Pennsylvania Philadelphia, suggested that the target of abagovomab – the CA-125 receptor – may not be the best avenue to approach ovarian cancer recurrence.

"CA-125-targeted immunotherapy based on antibody approaches does not appear to be a useful clinical strategy," Coucos said. He noted that oregovomab -- a cousin of abagovomab – also failed to produce positive results in ovarian cancer.

abstract: Uroepithelial (bladder/ureter) and kidney carcinoma in Lynch syndrome (MSH2)



Uroepithelial and kidney carcinoma in Lynch syndrome [Fam Cancer. 2012] - PubMed - NCBI
 
Fam Cancer. 2012 Apr 4

Abstract

Increased risk for urological tumors has been observed in mutation carriers with Lynch syndrome (LS). In this study, we evaluated the clinical features of uroepithelial (bladder and ureter) and kidney cancers in 974 Finnish mutation carriers. Altogether 30 patients had a total of 34 urological tumors: 12 ureter, 12 bladder, and 10 kidney cancers. Urological tumor was the only tumor in 9 (30 %) patients, and metachronous other tumor occurred in 21 (70 %). The occurrence of uroepithelial cancers was significantly higher in MSH2 mutation carriers (6 %) than in MLH1 carriers (2 %) and MSH6 mutation carriers (0 %).

The mean ages of patients at the time of diagnosis were: bladder cancer, 57 years; ureter cancer, 58 years; and kidney cancer, 64 years. Overall 5-year survival rates were 70 % in bladder cancer, 81 %  in ureter cancer, and 75 % in kidney cancer.

Cancer-specific 5-year survival rates were 70 %  in bladder cancer, 91 %  in ureter cancer, and 100 % in kidney cancer.

In conclusion, early age of onset was observed in patients with uroepithelial tumors, but not in patients with kidney cancer. The frequency of uroepithelial tumors was significantly higher in MSH2 mutation carriers than in MLH1 carriers. Further studies with larger numbers of patients, however, are needed to evaluate the potential benefit of surveillance of urological tumors in LS.

abstract: A systematic review of unmet needs of newly diagnosed older cancer patients undergoing active cancer treatment.



 Blogger's Note: the abstract does not indicate the determinate of 'older'

 Abstract

PURPOSE:

The aim of this study is to systematically review evidence with regard to answering the following questions: (1) What are the unmet care needs of older persons diagnosed with cancer who are undergoing active cancer treatment? (2) What are the predictors of unmet needs of older persons while undergoing active cancer treatment?

METHODS:

A systematic review of the literature published between January 1996 and December 2010 was completed. Manuscripts could be published in English, French, Dutch, or German searching the Medline, Embase, Psychinfo, Cinahl, and the Cochrane Library databases.

RESULTS:

Thirty studies were included. A significant proportion of newly-diagnosed patients undergoing cancer treatment had unmet needs, ranging from 15 to 93 %. The most common needs varied by study but included psychological needs, information needs, and needs in the physical domain. Most studies showed that the level of unmet needs was highest after diagnosis and start of treatment and decreased over time. Predictors of unmet needs included: younger age, female gender, depression, physical symptoms, marital status, treatment type, income, and education.

CONCLUSIONS:

The level of unmet needs in newly diagnosed older cancer patients after the start of treatment is high, and the most common needs are psychological and information needs. More research is needed which would focus on the needs of older adults with comorbid conditions, and how these comorbid conditions influence the level of unmet needs.