abstract: A systematic review evaluating the relationship between progression free survival and post progression survival in advanced ovarian cancer

 Blogger's Note:
this is and has been an ongoing issue in clinical trials as most use still use overall survival (OS) (as per this paper and others)  as the endpoint as opposed to progression free survival; it is a technical debate having wide implications for ovarian cancer treatments/patients, without access to the full text paper and based on the abstract alone,  one outstanding issue would be the impact of QOL/side effects/number of prior treatments, so in plain english as an example - clinical trial x includes standard treatment vs other, no more than eg. 3 prior chemos would be a component of the clinical trial - therefore - what was/is the mix of patients in the trial - all of which impact survival ratios irrespective of PFS/OS; opinions as usual are welcome
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A systematic review evaluating the relationship between progression free survival and post progression survival in advanced ovarian cancer:




Objective 
Although overall survival is the ultimate goal of cancer therapy, many clinical and health economic decisions are taken when only progression free survival (PFS) data are available. This study evaluates the relationship between PFS and post progression survival (i.e. the time between disease progression and death) to estimate how many months a new drug for ovarian cancer might add to overall survival if the number of months the drug added to PFS (relative to a standard drug) was already known.

Methods 
A literature search was conducted over Medline for randomised controlled trials published between January 1990 and July 2010 that evaluated the effect of a drug treatment in comparison to alternative drug treatment in patients with either advanced stage primary or recurrent ovarian cancer.
A systematic review of progression free and post progression survival (PPS) was performed. The relationship between PFS and PPS was evaluated by a graphical method and standard statistical tests.

Results
Thirty-seven trials involving 15,850 patients met the inclusion criteria. The review found that increases in median PFS generally lead to little change in post-progression survival. Percentage gains in PFS are generally associated with no percentage gains or with very slight percentage gains or losses in post-progression survival

Conclusion
If the effect of a new drug treatment for ovarian cancer is to extend median PFS by x months, then it is reasonable to estimate that the treatment will also extend median overall survival by x months. This information will be useful for individual and collective decision making.

abstract: Clinical characteristics and outcomes of BRCA-associated ovarian cancer: genotype and survival.

Clinical characteristics and outcomes of BRCA-associated ovarian cancer: genotype and survival

Cancer Genet. 2012 Jan;205(1-2):34-41


Abstract
Previous studies have suggested that BRCA-related epithelial ovarian cancer (EOC) conveys improved survival compared with that of sporadic EOC, but few studies have evaluated differences between BRCA genotypes.

We compared characteristics and outcome by genotype in BRCA-associated EOC. Patients with BRCA-associated EOC who were diagnosed between January 30,1981, and December 30, 2008, were retrospectively identified through institutional review board-approved registry studies. We examined clinical characteristics, including event-free survival (EFS) and overall survival (OS), for BRCA1 versus BRCA2 patients. We identified 197 cases (148 BRCA1 cases; 49 BRCA2 cases); the median follow-up period was 63 months. BRCA2 patients were older (55.4 vs. 51.1 y) and had fewer poorly differentiated tumors (67% vs. 82%). No difference in EFS was observed. OS at 5 years was 75% in BRCA2 patients versus 61% in BRCA1 patients; this was not statistically significant. A non-significant trend toward improved OS was observed in BRCA2 patients with advanced-stage disease (hazard ratio = 0.59; 95% confidence interval 0.32-1.08).

Age and grade differed significantly between BRCA1 and BRCA2 carriers in our study population. Whereas no overall differences in EFS or OS were observed, there was a trend toward improved OS in BRCA2 carriers with advanced-stage disease.

This may reflect important differences between BRCA genotypes and should be validated in larger studies.

abstract: Predictive value of serum CA-125 levels in patients with persistent or recurrent epithelial ovarian cancer or peritoneal cancer treated with Bevacizumab (Avastin) Gynecologic Oncology Group phase II trial

Purpose

To compare two methods of determining therapeutic response and disease progression — modified Gynecologic Cancer Intergroup (GCIG) criteria based on CA-125 and Radiographic Evaluation Criteria in Solid Tumors (RECIST), in a phase II trial of bevacizumab for patients with recurrent or persistent epithelial ovarian and peritoneal carcinoma.

Results

Sixty-two patients were evaluable by RECIST, 59 for progression by CA-125, and 45 for response by CA-125..........

Conclusions

In this study, disease assessment by RECIST and CA-125 appears to correlate in general. However, approximately 10% of patients might demonstrate progression earlier by CA-125.

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Highlights

► CA125-defined response and progression were assessed for women with recurrent ovarian cancer.
► CA125 and RECIST-defined response and progression correlated in most cases, but CA125 progression significantly preceded RECIST in 8 cases.
► CA125-defined response to bevacizumab was associated with a statistically significant correlation with overall survival.

abstract: The association between quality of life domains and overall survival in ovarian cancer patients during adjuvant chemotherapy: patients from GOG 172 trial

Highlights

► Physical QOL is associated with OS in ovarian cancer patients receiving adjuvant chemotherapy.
► Poor physical well-being at baseline is associated with risk of death in patients undergoing adjuvant chemotherapy for advanced ovarian cancer.
► Identifying modifiable characteristics that are associated with survival offers the potential for providing support that may improve outcomes.

open access: 2011 Progression-free survival in advanced ovarian cancer: a Canadian review and expert panel perspective | Dr A. Oza | Current Oncology (topics: eg chronic disease, 1st line therapy...)

Blogger's Note: may require registration (free); note also list of useful (international) reference papers

                                                                                        


Ovarian cancer is leading cause of gynecologic cancer mortality in Canada. To date, overall survival ( os ) has been the most-used endpoint in oncology trials because of its relevance and objectivity. However, as a result of various factors, including the pattern of sequential salvage (outdated term)  therapies, measurement of os and collection of os data are becoming particularly challenging. Phase ii and iii trials have therefore adopted progression-free survival ( pfs ) as a more convenient surrogate endpoint; however, the clinical significance of pfs remains unclear. This position paper presents discussion topics and findings from a pan-Canadian meeting of experts that set out to

• evaluate the relevance of pfs as a valid endpoint in ovarian cancer;
• reach a Canadian consensus on the relevance of pfs in ovarian cancer; and
• try to address how pfs translates into clinical benefit in ovarian cancer.
  
  
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Recommendations for future investigations include these:

• Ensure that trials are designed to evaluate pfs , os , and other clinically relevant endpoints such as disease-related symptoms or qol .
• Incorporate interim futility analyses intended to stop accrual early when the experimental regimen is not active.
• Stop trials early to declare superiority only when compelling evidence suggests that a new treatment provides benefit for a pre-specified clinically relevant endpoint such as os or symptom relief.
• Importantly, discourage early release of secondary endpoint results when such a release might increase the frequency of crossover to the experimental intervention.

abstract JCO: At What Cost Does a Potential Survival Advantage of Bevacizumab Make Sense for the Primary Treatment of Ovarian Cancer? A Cost-Effectiveness Analysis

Abstract

Purpose 

To determine whether the addition of bevacizumab to paclitaxel and carboplatin for the primary treatment of advanced ovarian cancer can be cost effective.

 Conclusion:

  The addition of bevacizumab to standard chemotherapy in patients with advanced ovarian cancer is not cost effective. Treatment with maintenance bevacizumab leads to improved PFS but is associated with both direct and indirect costs. The cost effectiveness of bevacizumab in the adjuvant treatment of ovarian cancer is primarily dependent on drug costs.

10-year analysis of the ATAC trial: wrong conclusion? : The Lancet Oncology

"The 10-year analysis of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial1 continues to show a difference in its primary endpoint of disease-free survival, which favours anastrozole as adjuvant treatment for postmenopausal women with hormone-responsive breast cancer. Ultimately, however, clinical trials have two aims: either to show improvement in survival, or in its quality.
Anastrozole has failed to meet these criteria when compared with tamoxifen."

abstract: Centralized treatment of advanced stages of ovarian cancer improves survival: a nationwide Danish survey

"...Treatment in a referral center was an independent prognostic factor for overall survival hazard ratio, 0.83 (confidence interval 0.70-0.98).  
Conclusion. Patients with stage IIIC and IV ovarian cancer benefit from treatment in a tertiary referral center."

abstract/full access: Cancer survival in Australia, Canada, Denmark, Norway, Sweden, and the UK, 1995–2007 (the International Cancer Benchmarking Partnership): an analysis of population-based cancer registry data : The Lancet

Note: Full access to article is free after registration (free)


"Background

Cancer survival is a key measure of the effectiveness of health-care systems. Persistent regional and international differences in survival represent many avoidable deaths. Differences in survival have prompted or guided cancer control strategies. This is the first study in a programme to investigate international survival disparities, with the aim of informing health policy to raise standards and reduce inequalities in survival.  

Methods Data from population-based cancer registries in 12 jurisdictions in six countries were provided for 2·4 million adults diagnosed with primary colorectal, lung, breast (women), or ovarian cancer during 1995—2007, with follow-up to Dec 31, 2007.

Improved Overall Survival with 12 Cycles of Single-Agent Paclitaxel Maintenance Therapy following a Complete Response to Induction Chemotherapy in Advanced Ovarian Carcinoma

Abstract
 
Objectives:
Previously reported studies have suggested that maintenance therapy in the treatment of ovarian cancer may provide progression-free survival (PFS) benefits, although they have not discerned a similar impact on patient overall survival (OS).

Methods: We examined the long-term PFS and OS of a previous study population consecutively treated with either 3 cycles (group A; n = 13 patients) or 12 cycles (group B; n = 13) of paclitaxel (135 mg/m²; Q21 days) maintenance therapy. Eligible patients received maintenance chemotherapy following a complete response to 6 cycles of primary induction chemotherapy, comprising 6 cycles of carboplatin (AUC = 5), paclitaxel (175 mg/m²), and gemcitabine (800 mg/m²) per protocol.  

Results: There were statistically significant PFS differences between group A (12 months) and group B (24 months) (p = 0.016). Moreover, the OS in group A was 38 months and 80 months for group B (p = 0.012). Current follow-up for this patient population exceeds 58 months.  

Conclusions: In the present investigation, 12 cycles of single agent paclitaxel maintenance therapy were associated with improved patient PFS and OS benefits. Despite contradictory reports, paclitaxel-based maintenance therapy may favorably impact both PFS and OS in advanced ovarian cancer patients who obtain a complete response to primary induction chemotherapy.

full access: Ovarian Cancer Metastatic to the Breast Presenting as Inflammatory Breast Cancer: A Case Report and Literature Review - Journal of Cancer

Conclusion. Although ovarian metastasis to the breast presenting as inflammatory breast cancer is rare, it should be included in the differential diagnosis for any patient with a personal history of ovarian cancer. Accurate differentiation is necessary because treatment differs significantly for patients with ovarian metastasis to the breast, as compared with patients with primary inflammatory breast cancer. Ovarian metastasis to the breast confers a poor prognosis...cont'd

Recurrent Ovarian Cancer: Use of Contrast-enhanced CT and PET/CT to Accurately Localize Tumor Recurrence and to Predict Patients’ Survival1 — Radiology

Abstract

Purpose: To compare accuracy and interobserver variability in the detection and localization of recurrent ovarian cancer with contrast material–enhanced (CE) computed tomography (CT) and positron emission tomography (PET)/CT and determine whether imaging findings can be used to predict survival.

Conclusion: Preliminary data suggest that CE CT and PET/CT may have similar accuracy in detection of recurrent ovarian cancer. Tumor size, number, and SUVmax may have potential as prognostic biomarkers for patients with recurrent ovarian cancer.

Characteristics and survival associated with ovarian cancer diagnosed as first cancer and ovarian cancer diagnosed subsequent to a previous cancer

Abstract

Objective:
To examine the risk of subsequent primary ovarian cancer among women diagnosed previously with cancer (subsequent cohort) and to compare demographic and tumor characteristics affecting overall survival of these women and women diagnosed with first primary ovarian cancer (index cohort).


Methods: 
We identified the two cohorts of women using the 1973-2005 Surveillance, Epidemiology and End Results (SEER) result data. We calculated relative risk of subsequent primary ovarian cancer and estimated 5-year risks of dying (hazard-ratios) after diagnosis of the first or subsequent primary ovarian cancer in the two cohorts, respectively using Cox modeling.


Results:
Women diagnosed with index cancers of the corpus uteri, colon, cervix, and melanoma at age younger than 50 had increased risk of ovarian cancer within 5 years after diagnosis (p<0.05); young breast cancer survivors had continued risk beyond 20 years. In 5-year follow-up survival analysis, the factors associated with a better survival (p<0.05) were similar in both cohorts and included more recent diagnosis; localized or regional disease; age <50 years at diagnosis; and being white versus black. A lower risk of dying from mucinous, endometrioid, or non-epithelial tumors than from serous was seen after 15 months (p<0.01), or after 32 months from diagnosis of the index and subsequent cohorts, respectively. (clear cell??)


Conclusions:
Age, stage, and histology affect ovarian cancer survival. The increased risk of ovarian cancer over time, especially among breast and colon cancer survivors who are less than 50 years of age, suggests common etiologies and necessitates careful surveillance by health care providers and increased survivors awareness through educational efforts.

Abstract: The role of body mass index, physical activity, and diet in colorectal cancer recurrence and survival: a review of the literature.

"In conclusion, only a paucity of data is available about the effect of dietary and other lifestyle factors on colorectal cancer recurrence and survival. Thus far, no clear conclusions can be drawn. Future studies are warranted, particularly on postdiagnosis BMI and diet."

Racial differences in stage at diagnosis and survival from epithelial ovarian cancer: A fundamental cause of disease approach

Social Science & Medicine

abstract:

Associations between race, socioeconomic status (SES) and health outcomes have been well established. One of the ways in which race and SES affect health is by influencing one’s access to resources, which confers ability to avoid or mitigate adverse outcomes. The fundamental cause of disease approach argues that when a new screening tool is introduced, individuals with greater resources tend to have better access to the innovation, thus benefiting from early detection and leading to better survival.  

Conversely, when there is no established screening tool, racial and SES differences in early detection may be less pronounced.

Most ovarian cancer is diagnosed at advanced stages, because of the lack of an effective screening tool and few early symptoms. However, once detected, racial differences may still be observed in mortality and survival outcomes. We examined the racial differences in diagnosis and survival among ovarian cancer cases diagnosed during 1994–1998, in Cook County, Illinois (N = 351). There were no racial differences in the stage at diagnosis: 51.7% of white and 52.9% of black women were diagnosed at later stages (III and IV). Only age was associated with the stage at diagnosis. Tumor characteristics also did not differ between white and black women. Compared to white women, black women were less likely to be married, less educated, more frequently used genital powder, had tubal ligation, and resided in higher poverty census tracts. As of December 31, 2005, 44.3% of white and 54.5% of black women had died of ovarian cancer. Controlling for known confounding variables, the hazard ratio for ovarian cancer death between black and white women was 2.2. The findings show that fundamental cause perspective provides a potential framework to explore subtleties in racial disparities, with which broader social causes may be accounted for in explaining post diagnosis racial differences.

Obesity is associated with improved survival in patients with organ-confined clear-cell kidney cancer (see 'Note')

Note: while not ovarian cancer specific (noting the common cell type of clear cell) the conclusion is interesting

CONCLUSION: We identified overweight as an independent prognostic marker of improved cancer specific survival in patients with organ-confined but not advanced RCC. Basic research is required to resolve the dilemma of why, if a higher BMI predisposes to RCC, it concurrently prolongs survival after patients have undergone (partial) nephrectomy.

abstract: Examining the potential relationship between multidisciplinary cancer care and patient survival: An international literature review

CONCLUSIONS: Due to methodological limitations, this review is unable to assert a causal relationship between multidisciplinary care and patient survival

abstract: Measuring the effect of including multiple cancers in survival analyses using data from the Canadian Cancer Registry

Background: In survival analyses using cancer registry data, second and subsequent primary cancers diagnosed in individuals are typically excluded.

Conclusion: Inclusion of second and subsequent primary cancers in the analysis tended to lower estimates of relative survival, the extent of which varied by cancer and age and depended in part on the proportion of first primary cancers.

abstract: The Clinical Molecular Diagnostics Laboratory and Microsatellite Instability Testing of Colorectal Cancer

Note: this abstract gives an overview of Lynch Syndrome testing eg. immunohistochemistry (testing of tumour); Microsatellite (MSI); improved survival rates, treatment options (relating to test results)

Oncologist preferences for health States associated with the treatment of advanced ovarian cancer - (interview with 34 oncologists) - abstract

Objective:
"To explore oncologists' preferences for hypothetical outcome scenarios (i.e. health states) resulting from various treatment options."
Conclusions:
"These data suggest that oncologists may choose treatments that maximize clinical efficacy only when not associated with severe toxicities or low emotional well-being unless associated with a large improvement in efficacy. Physicians may prefer a more toxic chemotherapy regimen that improves survival, and are more willing to compromise emotional well-being for a large survival advantage in the setting of newly diagnosed disease. Slight improvements in clinical efficacy may not be acceptable to oncologists unless associated with higher emotional well-being for the patient."