paywalled: Limited prognostic value of tissue protein expression levels of cyclin E in Danish ovarian cancer patients: from the Danish ‘MALOVA’ ovarian cancer study

Limited prognostic value of tissue protein expression levels of cyclin E in Danish ovarian cancer patients: from the Danish ‘MALOVA’ ovarian cancer study

The primary objective of this study was to assess the expression of cyclin E in tumour tissues from 661 patients with epithelial ovarian tumours. The second was to evaluate whether cyclin E tissue expression levels correlate with clinico-pathological parameters and prognosis of the disease. Using tissue arrays (TA), we analysed the cyclin E expression levels in tissues from 168 women with borderline ovarian tumours (BOT) (147 stage I, 4 stage II, 17 stage III) and 493 Ovarian cancer (OC) patients (127 stage I, 45 stage II, 276 stage III, 45 stage IV). Using a 10% cut-off level for cyclin E overexpression, 20% of the BOTs were positive with a higher proportion of serous than mucinous tumours. Sixty-two per cent of the OCs were positive for cyclin E expression with the highest percentage found in clear cell carcinomas. 

Results based on univariate and multivariate survival analyses with a 10% cut-off value showed that cyclin E had no independent prognostic value. In conclusion, we found cyclin E expression in tumour tissue to be of limited prognostic value to Danish OC patients.

pdf: Summaries for Patients - Surrogate Decision Makers’ Interpretation of Prognostic Information

Surrogate Decision Makers’ Interpretation of Prognostic Information

What are the implications of the study?

Inaccurate interpretations of doctors’ prognostications arise partly from optimistic biases rather than simply from misunderstandings. Helping surrogates attain realistic expectations about patients’ likely outcomes is more complex than just giving clear information.

Weighing the Chances at Life's End - NYTimes.com

Weighing the Chances at Life's End - NYTimes.com


"........But the grimmer the prognosis, the more inaccurate and more optimistic the surrogates’ responses became. Only 22 percent correctly interpreted a statement about what a “5 percent chance of surviving” meant, while 65 percent answered with greater optimism.
“They clearly grasped the meaning of these statements,” Dr. White said. “They were not misunderstanding the numbers. They weren’t misunderstanding the language.” If that had been the case, you’d expect them to have been inaccurate about good news, too.
Instead, relatives hearing doctors deliver dire prognoses just didn’t accept or believe them. They displayed, in medspeak, “a systematic optimism bias.”
Such bias has shown up many times before in the medical literature. Cancer patients enrolled in early phases of clinical trials, for instance,....."

Clinical Oncology News (ethics) - Would You Be ‘Surprised’: "The Surprise Question" (prognosis)

The Surprise Question

"We turn to the problem of uncertainty and its impact on providing information. Recently, investigators have studied the “surprise” question, an interesting approach to making better survival predictions. The approach is somewhat ironic because although the question is subjective in nature, it tends to produce a good objective response. When physicians are asked to judge survival time, they tend to be inaccurate even when using the best prognostication information, including comorbidities, staging, advance directive status and whether the cancer has metastasized.

However, a recent study revealed that physicians are more accurate when they answer the surprise question: “Would I be surprised if this patient died in the next year?” A negative answer indicates an expectation of death within a year, whereas an affirmative answer indicates the physician’s gut response that the patient is highly likely to be alive within a year.¹ In a study of 826 cancer patients, an affirmative answer proved “correct” in 97% of the responses; almost all of the patients with a “yes” response to the question were alive within a year......"

Biomedcentral: open access - Biomarker robustness reveals the PDGF network as driving disease outcome in ovarian cancer patients in multiple studies

link:    ABSTRACT and open text PDF
Background:
Ovarian cancer causes more deaths than any other gynecological cancer.
Identifying the molecular mechanisms that drive disease progress in ovarian cancer is a critical step in providing therapeutics, improving diagnostics, and affiliating clinical behavior with disease etiology. Identification of molecular interactions that stratify prognosis is key in
facilitating a clinical-molecular perspective.

Results:  
The Cancer Genome Atlas has recently made available the molecular characteristics of more than 500 patients......

Blogger's Note: see also - The Cancer Genome Atlas completes detailed ovarian cancer analysis  NCI Press Release (2011)

CONCLUSIONS
"..........Over the past few decades, different genes have been used, with greater or lesser success, as biomarkers for prognostics. In the work presented here, by performing genome-wide sequential
analyses across all genes and across all pathways, starting with TCGA and validating in two additional datasets, we saw how the single-gene approach fails to stratify patients robustly into prognostic groups.


"Our results demonstrate that pathway interactions are either associated with improved prognosis by "helping" the pathway counter the tumor, or with poor prognosis by "breaking down" the pathway's normal activity. Through better understanding of the pathway mechanisms and the interactions that undergo changes, we may find targets for new treatments. The fact that the pathway we identified did not correlate with age or tumor diameter and was found in all
three datasets strengthens the hypothesis that this pathway is a core mechanism of the disease."

abstract : Circulating tumor cells predict progression free survival and overall survival in patients with relapsed/recurrent advanced ovarian cancer - multinational trial

Objective

Serial circulating tumor cell (CTC) counts have demonstrated predictive and prognostic value in patients with metastatic breast, colorectal, and prostate cancer.
In a phase III study of pegylated liposomal doxorubicin (PLD) with trabectedin vs. PLD for relapsed ovarian cancer, we evaluated the correlation, if any, between numbers of CTCs and progression free survival, (PFS) and overall survival (OS).

Conclusions
Results from this study indicate that elevated numbers of CTCs impart an unfavorable prognosis for ovarian cancer patients.

Research highlights

► Circulating tumor cells (CTCs) are prognostic during ovarian cancer therapy.
► Ovarian cancer patients with baseline ≥ 2 CTCs had shorter overall survival time.
► Patients with baseline ≥ 2 CTCs had shorter time to disease progression.

Nuclear P27 (gene) expression in benign, borderline (LMP) and invasive tumors of the ovary and its association with prognosis: A GOG group study

Abstract

Objective

Nuclear p27 expression was examined in non-invasive and invasive ovarian tumors from a cross-sectional study, and clinical relevance of p27 was evaluated in the primary tumors from women participating in two randomized phase III treatment trials.

Methods

An immunohistochemistry assay was used to detect p27 in formalin-fixed paraffin-embedded ovarian tumors from 3 distinct sources.

Research Highlights

► Low p27 expression is associated with malignant transformation of the ovary.
► A cyclin E to p27 ratio > 1.0 may be associated with shorter survival.
► Study required confirming increased recurrences with low p27 in early stage patients.

Breast cancer classification algorithm to identify 20 gene signature developed using Microsoft Excel

"....The 10 most highly ranked genes predictive of poor prognosis and those 10 genes most highly predictive of good prognosis established a 20-gene expression based predictor, which was found to perform as well as two other models in the validation group. According to Hassell, "Our algorithm produces prediction models with comparable accuracy to other feature selection techniques while having generally better accessibility and useability for biological research scientists. We've begun using our algorithm to generate gene expression based prediction models of breast cancer cell sensitivity to commonly used anti-cancer therapies"....cont'd

Upstaging pathologic stage I ovarian carcinoma based on dense adhesions is not warranted: A clinicopathologic study of 84 patients originally originally classified as FIGO stage II

Note: very interesting study, albeit abstract

 

Abstract

BACKGROUND: 

FIGO stage II ovarian cancer comprises 8% of ovarian cancers. It is a common but not universal practice to upstage densely adherent pathologic stage I tumors to stage II. FIGO guidelines are not clear, and data supporting this practice are sparse.

METHODS:

We retrospectively reviewed patients with stage II ovarian cancer and grouped them based upon histologic evidence of extraovarian extension. Tumors densely adherent to extraovarian structures but without histologic tumor outside the ovary were considered pathologic stage I. All others were considered surgical-pathologic stage II. Three histologic patterns of extraovarian tumor involvement were identified.

RESULTS:

Eighty-four patients were studied. Twenty-four patients had pathologic stage I disease and 60 had histologic evidence of extraovarian pelvic spread and were surgical-pathologic stage II. The 5-year survival for stage I was 100%, and the median survival was not reached. The 5-year survival for those with surgical-pathologic stage II disease was 56.8% and the median survival was 73months. There were no differences observed based upon pattern of extraovarian spread. The survival difference between pathologic stage I and surgical-pathologic stage II was significant (p<0.001). There were no differences seen in 5-year survival among surgical-pathologic stage II patients with serous, endometrioid or clear cell histologies (64.5%, 64.8% and 64.3% respectively).

CONCLUSION:

These retrospective data suggest that the practice of upstaging densely adherent pathologic stage I tumors to stage II may not be warranted. Cell type is not a prognostic factor in stage II.

Germline Genetic Variation, Cancer Outcome, and Pharmacogenetics -- abstract (references Lynch/BRCAs)

ABSTRACT
Studies of the role of germline or inherited genetic variation on cancer outcome can fall into three distinct categories. First, the impact of highly penetrant but lowly prevalent mutations of germline DNA on cancer prognosis has been studied extensively for BRCA1 and BRCA2 mutations as well as mutations related to hereditary nonpolyposis colorectal cancer syndrome (Lynch Syndrome). These mainly modest-sized analyses have produced conflicting results. Although some associations have been observed, they may not be independent of other known clinical or molecular prognostic factors. Second, the impact of germline polymorphisms on cancer prognosis is a burgeoning field of research. However, a deeper understanding of potentially confounding somatic changes and larger multi-institutional, multistage studies may be needed before consistent results are seen. Third, research examining the impact of germline genetic variation on differential treatment response or toxicity (pharmacogenetics) has produced some proof-of-principle results. Putative germline pharmacogenetic predictors of outcome include DPYD polymorphisms and fluorouracil toxicity, UGT1A1 variation and irinotecan toxicity, and CYP2D6 polymorphisms and tamoxifen efficacy, with emerging data on predictors of molecularly targeted or biologic drugs. Here we review data pertaining to these germline outcome and germline toxicity relationships. (full text requires $$/subscription)

Weight, Physical Activity, Diet, and Prognosis in Breast and Gynecologic Cancers JCO (abstract)

ABSTRACT

Diet, physical activity, and weight may affect prognosis among women who are diagnosed with breast or gynecologic cancer. Observational studies show associations between being overweight or obese and weight gain with several measures of reduced prognosis in women with breast cancer and some suggestion of poor prognosis in underweight women. Observational studies have shown an association between higher levels of physical activity and improved breast cancer–specific and all-cause mortality, although a dose-response relationship has not been established. One large randomized controlled trial reported increased disease-free survival after a mean of 5 years in patients with breast cancer randomly assigned to a low-fat diet versus control. However, another trial of similar size found no effect from a high vegetable/fruit, low-fat diet on breast cancer prognosis. The few reported studies suggest that obesity negatively affects endometrial cancer survival, while the limited data are mixed for associations of weight with ovarian cancer prognosis. Insufficient data exist for assessing associations of weight, physical activity, or diet with prognosis in other gynecologic cancers. Associations of particular micronutrient intake and alcohol use with prognosis are not defined for any of these cancers. The effects of dietary weight loss and increase in physical activity on survival or recurrence in breast and gynecologic cancers are not yet established, and randomized controlled trials are needed for definitive data.

Understanding Prognosis and Cancer Statistics - National Cancer Institute

"Because survival rates are based on large groups of people, they cannot be used to predict what will happen to a particular patient. No two patients are exactly alike, and treatment and responses to treatment vary greatly."

Weight, Physical Activity, Diet, and Prognosis in Breast and Gynecologic Cancers --JCO (abstract)

ABSTRACT
Diet, physical activity, and weight may affect prognosis among women who are diagnosed with breast or gynecologic cancer. Observational studies show associations between being overweight or obese and weight gain with several measures of reduced prognosis in women with breast cancer and some suggestion of poor prognosis in underweight women. Observational studies have shown an association between higher levels of physical activity and improved breast cancer–specific and all-cause mortality, although a dose-response relationship has not been established. One large randomized controlled trial reported increased disease-free survival after a mean of 5 years in patients with breast cancer randomly assigned to a low-fat diet versus control. However, another trial of similar size found no effect from a high vegetable/fruit, low-fat diet on breast cancer prognosis. The few reported studies suggest that obesity negatively affects endometrial cancer survival, while the limited data are mixed for associations of weight with ovarian cancer prognosis. Insufficient data exist for assessing associations of weight, physical activity, or diet with prognosis in other gynecologic cancers. Associations of particular micronutrient intake and alcohol use with prognosis are not defined for any of these cancers. The effects of dietary weight loss and increase in physical activity on survival or recurrence in breast and gynecologic cancers are not yet established, and randomized controlled trials are needed for definitive data.

The National Cancer Database report on advanced-stage epithelial ovarian cancer: Impact of hospital surgical case volume on overall survival and surgical treatment paradigm

Abstract

OBJECTIVE: To examine the effect of hospital procedure volume and other prognostic variables on overall survival outcome and likelihood of receiving standard recommended care among patients with advanced-stage epithelial ovarian cancer.
CONCLUSIONS: Hospital ovarian cancer surgical volume >/=21 cases/year is associated with a higher likelihood of patients with Stage IIIC/IV epithelial ovarian cancer receiving standard treatment (surgery followed by adjuvant chemotherapy). Even after adjusting for treatment paradigm and other factors, hospital volume >/=21 cases/year was significantly predictive of improved overall survival outcome.

Associations between age and quality of life in advanced ovarian cancer

Background:
..... Few studies have examined whether age influences advanced ovarian cancer patients' prognostic understanding or quality of life at the time of diagnosis."

'The worst thing about hospice is that they talk about death': contrasting hospice decisions and experience among immigrant Central and South American Latinos with US-born White, non-Latino cancer caregivers

Abstract:
Hospice care is promoted as a model for improving end of life care and decreasing burden on caregivers. However, hospice use is low in Latinos and little is known about how Latinos make hospice decisions and experience hospice once enrolled. Qualitative methods were used in this study to conduct in-depth interviews and focus groups with 15 Latino bereaved hospice family caregivers and 15 White non-Latino bereaved hospice family caregivers to describe hospice experiences and evaluate whether cultural factors affected the experience. Differences in decision-making and caregiving experience were identified that were influenced by culture. For example, cultural values of denial, secrecy about prognosis and a collective, family-centered system influenced hospice decisions and experience in Latinos but not non-Latinos. This study identifies a significant dilemma: that is, how to discuss hospice with a patient and family who prefer not to discuss a terminal prognosis. Future research is needed to extend these preliminary results; such results may be useful for designing interventions to improve end of life care and caregiving in Latinos.

Giving Honest Information to Patients With Advanced Cancer Maintains Hope - Cancer Network

"Background: Oncologists often do not give honest prognostic and treatment-effect information to patients with advanced disease. One of the primary reasons stated for witholding this information is to “not take away hope.” We could find no study that tested if hope was influenced by honest clinical information...cont'd"

from the series The Art of Oncology: "Certain Death in Uncertain Time: Informing Hope by Quantifying a Best Case Scenario"

Note: Stephen Gould's writings were extraordinarily popular died in 2002)

"Research informs us that the majority of patients with metastatic cancer desire information about their likely survival duration. The literature also recommends that prognostic information be communicated to those who request it in a manner that is meaningful and realistic, but maintains hope.....The following edited extract from Edward Kennedy’s memoir (and others) conveys the importance of trying to answer these questions....."

"...But I wasn’t willing to accept the doctor’s prognosis for two reasons. The first was my own obstinate will to carry on in the face of adversity, one of the many habits of discipline that my father instilled in me…. The second was the way the message was delivered. Frankly, it made me furious. I am a realist, and I have heard bad news in my life. I don’t expect or need to be treated with kid gloves. But I do believe in hope...."

"....As Stephen Gould published 3 years after reading that his median survival with abdominal mesothelioma was 8 months, “the median isn’t the message.”7 He argued that median survival can be both misleading and discouraging and believed few people have sufficient understanding of statistics to evaluate what the term median
really means....."

Follow-Up Study of the Correlation Between Postoperative Com... : International Journal of Gynecological Cancer

Follow-Up Study of the Correlation Between Postoperative Computed Tomographic Scan and Primary Surgeon Assessment in Patients With Advanced Ovarian, Tubal, or Peritoneal Carcinoma Reported to Have Undergone Primary Surgical Cytoreduction to Residual Disease of 1 cm or Smaller

Conclusions: On this follow-up analysis, only age, stage, and residual disease were significant prognostic factors for overall survival. Discordant findings between the primary surgeon's assessment and the postoperative CT scan findings of residual disease was not an independent prognostic factor.

Serum tetranectin is a significant prognostic marker in ovarian cancer patients.

Conclusion. Preoperative serum TN is a useful prognostic indicator of advanced stage for patients with OvCa.