paywalled: Gynecologic Oncology Impact of Complete Cytoreduction Leaving No Gross Residual Disease Associated with Radical Cytoreductive Surgical Procedures on Survival in Advanced Ovarian Cancer

Impact of Complete Cytoreduction Leaving No Gross Residual Disease Associated with Radical Cytoreductive Surgical Procedures on Survival in Advanced Ovarian Cancer

 Abstract

Background  

To analyze the impact of radical cytoreductive surgery—as part of primary tumor debulking—on the amount of residual tumor and survival in patients with advanced ovarian cancer and to evaluate the prognostic significance of no gross residual disease (RD) after surgery.

Methods  

Medical records of 203 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC–IV ovarian cancer were reviewed. All patients underwent primary cytoreductive surgery followed by taxane- and platinum-based chemotherapy. Various clinicopathologic characteristics were collected.

Results  

Of 203 patients, 119 patients underwent simple surgery, while radical surgery was performed in 84 patients..........

Conclusions  

No gross RD is associated with improved overall survival, and radical surgery was effective for achieving no gross RD.

 

paywalled: Is there any association between retroperitoneal lymphadenectomy and survival benefit in advanced stage epithelial ovarian carcinoma patients?

Is there any association between retroperitoneal lymphadenectomy and survival benefit in advanced stage epithelial ovarian carcinoma patients? 

Abstract

Aim:  The effect of systematic retroperitoneal lymphadenectomy (SRL) remains controversial in patients with advanced epithelial ovarian cancer (aEOC) who are optimally debulked.

Conclusion:  Our data suggest that aEOC patients with optimal cytoreduction who underwent SRL did not show a significant improvement in survival irrespective of each histological type.

abstract: Postoperative venous thromboembolism predicts survival in cancer patients

Postoperative venous thromboembolism predicts survi... [Ann Surg. 2012]

OBJECTIVES:

To determine whether a postoperative venous thromboembolism (VTE) is associated with a worse prognosis and/or a more advanced cancer stage and to evaluate the association between a postoperative VTE and cancer-specific survival when known prognostic factors, such as age, stage, cancer type, and type of surgery, are controlled.

CONCLUSIONS:

Postoperative VTE in oncology patients with limited disease and a complete surgical resection is associated with an inferior cancer survival. A postoperative VTE remains a poor prognostic factor, even when controlling for age, stage, cancer type, and surgical procedure further supporting an independent link between hypercoagulability and cancer survival.

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.

newswise: Pox Vaccines Extend Survival for Patients with Melanoma, Ovarian Cancer in U.S., German Studies

Pox Vaccines Extend Survival for Patients with Melanoma, Ovarian Cancer in U.S., German Studies

Released: 3/26/2012 3:05 PM EDT
Source: Roswell Park Cancer Institute

 

Newswise — BUFFALO, NY — An immunotherapy regimen incorporating poxviruses and targeting a particular tumor antigen, NY-ESO-1, has shown promise in treating two types of cancers. Kunle Odunsi, MD, PhD, Chair of the Department of Gynecologic Oncology and Director of the Center for Immunotherapy at Roswell Park Cancer Institute (RPCI), Elke Jäger, MD, Head of the Department of Oncology and Hematology at Krankenhaus Nordwest, Frankfurt, and colleagues today published results from two studies testing this approach in PNAS, the Proceedings of the National Academy of Sciences of the United States of America...........

REPOST: open access: Neoadjuvant Chemotherapy or Primary Surgery in Stage IIIC or IV Ovarian Cancer — NEJM (multi-national study)

Neoadjuvant Chemotherapy or Primary Surgery in Stage IIIC or IV Ovarian Cancer — NEJM

Original Article

Neoadjuvant Chemotherapy or Primary Surgery in Stage IIIC or IV Ovarian Cancer

N Engl J Med 2010; 363:943-953September 2, 2010

Letters

In most women with ovarian carcinoma, the disease is not diagnosed until it is at an advanced stage. Primary cytoreductive surgery is considered the standard of care for advanced ovarian carcinoma.1-4 However, data from prospective, randomized, controlled trials assessing the role of primary surgery in the treatment of such cases are lacking. Interval debulking surgery has not been viewed as beneficial in women with residual tumor that exceeds 1 cm in diameter after primary debulking surgery performed with the objective of maximal surgical effort by a gynecologic oncologist.5-7 As an alternative to primary debulking surgery followed by chemotherapy, some authors have investigated the use of neoadjuvant chemotherapy before cytoreductive surgery. However, results of a meta-analysis involving 835 patients suggested that neoadjuvant chemotherapy, as compared with primary debulking surgery, was associated with a worse outcome.8
We report on a randomized trial in which we compared primary debulking surgery followed by platinum-based chemotherapy and platinum-based neoadjuvant chemotherapy followed by interval debulking surgery and additional platinum-based chemotherapy in women with advanced ovarian carcinoma.............

abstract: Role of Definitive Radiation Therapy in Carcinoma of Unknown Primary in the Abdomen and Pelvis

Role of Definitive Radiation Therapy in Carcinoma of Unknown Primary in the Abdomen and Pelvis

 Objectives

Carcinoma of unknown primary (CUP) in the abdomen and pelvis is a heterogeneous group of cancers with no standard treatment. Considered by many to be incurable, these patients are often treated with chemotherapy alone. In this study, we determined the effectiveness of radiation therapy in combination with chemotherapy in patients with CUP in the abdomen and pelvis.

Patients and Methods

Medical records were reviewed for 37 patients with CUP treated with radiation therapy for disease located in the soft tissues and/or nodal basins of the abdomen and pelvis at the University of Texas M.D. Anderson Cancer between 2002 and 2009. All patients underwent chemotherapy, either before or concurrent with radiation therapy. Patients were selected for radiation therapy on the basis of histologic type, disease extent, and prior therapy response. Twenty patients underwent definitive radiation therapy (defined as radiation therapy targeting all known disease sites with at least 45 Gy) and 17 patients underwent palliative radiation therapy. Only 6 patients had surgical resection of their disease. Patient and treatment characteristics were extracted and the endpoints of local disease control, progression-free survival (PFS), overall survival (OS), and treatment-related toxicity incidence were analyzed.

Results

The 2-year PFS and OS rates for the entire cohort were 32% and 57%, respectively. However, in patients treated with definitive radiation therapy, the rates were 48% and 76%, and 7 patients lived more than 3 years after treatment with no evidence of disease progression. Nevertheless, radiation-associated toxicity was significant in this cohort, as 40% experienced Grade 2 or higher late toxicities.

Conclusions

The use of definitive radiation therapy should be considered in selected patients with CUP in the soft tissues or nodal basins of the abdomen and pelvis.

Carcinoma of unknown primary, Chemoradiation, Conformal radiation therapy, Intensity-modulated radiation therapy, Lymph node metastasis

Outcomes of surgical management of bowel obstruction in relapsed epithelial ovarian cancer (EOC)

Outcomes of surgical management of bowel obstruction in relapsed epithelial ovarian cancer (EOC):

Objective 
To describe the outcomes of surgical management of bowel obstruction in relapsed epithelial ovarian cancer (EOC) so as to define the criteria for patient selection for palliative surgery. Methods 90 women with relapsed EOC underwent palliative surgery for bowel obstruction between 1992 and 2008.

Conclusion 
Surgery for bowel obstruction in relapsed EOC is associated with a high morbidity and mortality rate especially in emergency cases when compared to other gynaecological oncological procedures. Palliation can be achieved in almost two thirds of cases, is equally likely in elective and emergency cases but is less likely in those with ascites.

abstract: Malignant ovarian germ-cell tumours

Malignant ovarian germ-cell tumours account for about 5% of all ovarian malignancies and typically present in the teenage years. They are almost always unilateral and are exquisitely chemosensitive. As such, the surgical approach in young women with such tumours confined to a single ovary should aim to preserve fertility.....

open access: paper/Editorial - Improvements in survival of gynaecological cancer in the Anglia region of England: are these an effect of centralisation of care and use of multidisciplinary management?

Blogger's Note:  search blog for additional information on centralization of ovarian cancer surgery (eg. Norway...)

 .........................................................
Setting 
In 1999 the DH (Department of Health) in England introduced the Improving Outcomes in Gynaecological Cancer guidance, advising case management by multidisciplinary teams with surgical concentration in specialist hospitals.

In conclusion, there was a highly significant step-change increase in survival in gynaecological cancers associated with the adoption of the 1999 national policy change. ......... These changes have been most marked within endometrial and ovarian cancers.

Editorial: 

"Finally, Crawford and Greenberg on page 160 present their detailed population-based analyses of the effects of centralisation of care on survival outcomes in endometrial and ovarian cancer. Introduced in the UK in the late 1990s, the development of Cancer Networks (the ‘hub and spoke’ model) met with considerable resistance. Although it seemed intuitively right, the evidence to support such health care re-organisations was best described as weak, and they not only needed a significant investment of resources, but also required people to travel away from their immediate locality, making it difficult for friends and families to visit. Now, a number of years on, data are beginning to emerge reassuring all of the interested parties, patients in particular, that the energies and efforts required to implement the principles of centralisation of cancer services appear to have been justified."

abstract: Prognostic Value of Biomarkers Related to Drug Resistance in Patients with Advanced Epithelial Ovarian Cancer

Prognostic Value of Biomarkers Related to Drug Resistance in Patients with Advanced Epithelial Ovarian Cancer:

Background/Aim:
We aimed to investigate the prognostic value of biomarkers [Ki-67, adenosine triphosphate-binding cassette sub-family B member 1 (ABCB1), adenosine triphosphate-binding cassette sub-family C member 1 (ABCC1), adenosine triphosphate-binding cassette sub-family C member 2 (ABCC2), p53, cyclin E and v-akt murine thymoma viral oncogene homolog 2 (AKT2)] in patients with advanced epithelial ovarian cancer (EOC).

Materials and Methods:
The levels of expression of biomarkers in tumor tissues of 47 patients with stage 3 or 4 EOC were estimated via immunohistochemical staining using tissue microarrays. The associations of biomarker expression with progression-free survival (PFS) and overall survival (OS) were evaluated using a log-rank test and Cox regression analysis.

Results:
Based on multivariate analysis, high expression of Ki-67 (p=0.003) and low expression of ABCC2 (p=0.048) were associated with a prolonged PFS. However, other biomarkers were not associated with PFS. Residual tumor <1 cm (p=0.023) and PFS >6 months (p=0.005) were associated with prolonged OS. However, none of the biomarkers were associated with OS. 

Conclusion: High expression of Ki-67 and low expression of ABCC2 appear to be useful as markers for prolonged PFS in patients with advanced EOC.

abstract: Implementing an online tool for genome-wide validation of survival-associated biomarkers in ovarian-cancer using microarray data from 1287 patients.

Abstract

"The validation of prognostic biomarkers in large independent patient cohorts is a major bottleneck in ovarian cancer research. We implemented an online tool to assess the prognostic value of the expression levels of all microarray quantified genes in ovarian cancer patients. First, a database was set up using gene expression data and survival information of 1,287 ovarian cancer patients downloaded from GEO and TCGA (Affymetrix HGU133A, HGU133A 2.0 and HGU133+2 microarrays).

After quality control and normalization only probes present on all three Affymetrix platforms were retained (n=22,277). To analyze the prognostic value of the selected gene, the patients are divided into two groups according to various quantile expressions of the gene. These groups are then compared using progression free survival (n=1,090) or overall survival (n=1,287). A Kaplan-Meier survival plot is generated and significance is computed. The tool can be accessed online at www.kmplot.com/ovar. We used this integrative data analysis tool to validate the prognostic power of 37 biomarkers identified in the literature.

Of these, CA125 (p=3.7e-5, HR=1.4), CDKN1B (p=5.4e-5, HR=1.4), KLK6 (p=0.002,HR=0.79), IFNG (p=0.004, HR=0.81), P16 (p=0.02, HR=0.66) and BIRC5 (p=0.00017, HR=0.75) were associated with survival. The combination of several probe sets can further increase prediction efficiency.

In summary, we developed a global online biomarker validation platform that mines all available microarray data to assess the prognostic power of 22,277 genes in 1,287 ovarian cancer patients.

We specifically used this tool to evaluate the effect of 37 previously published biomarkers on ovarian cancer prognosis."

Author Insights: BRCA1 and BRCA2 Gene Mutations Associated With Improved Ovarian Cancer Survival « news@JAMA

"....The pooled analysis of 26 observational studies involving 3879 women with ovarian cancer found 52% of women with a BRCA2 mutation were alive 5 years after diagnoses, as were 44% of women with a BRCA1 mutation........ The researchers noted that the survival advantage seen in women carrying a BRCA1 or BRCA2 mutation could be related to “intrinsic biological differences, their response to therapeutic agents, or both.”"

Conclusion Among patients with invasive EOC, having a germline mutation in BRCA1 or BRCA2 was associated with improved 5-year overall survival. BRCA2 carriers had the best prognosis. 

abstract: Significance of Perioperative Infection in Survival of Patients With Ovarian Cancer

Objectives:
Perioperative infectious diseases comprise some of the most common causes of surgical mortality in women with ovarian cancer. This study was aimed to evaluate the significance of perioperative infections in survival of patients with ovarian cancer.

Conclusion:

Perioperative infectious disease comprises an independent risk factor for survival of patients with ovarian cancer.

"Perioperative infections were associated with increased surgical mortality, delay in chemotherapy treatment, decreased chemotherapy response, shorter progression-free survival) and decreased overall survival ." (Blogger's note - stats removed for ease of reading)

open access: Letter: Survival Is Not a Good Outcome for Randomized Trials With Effective Subsequent Therapies

Link to Letter

 REFERENCES (original article)

1. ↵
   1. Korn EL,
   2. Freidlin B,
   3. Abrams JS

   (2011) Overall survival as the outcome for randomized clinical trials with effective subsequent therapies. J Clin Oncol 29:2439–2442.

   Abstract/FREE Full Text

abstract : The effect of sleep disturbance on quality of life in women with ovarian cancer

"PSQI was not correlated with age, time since diagnosis, number of previous chemotherapy regimens. PSQI score did not differ by current disease or chemotherapy status."

Highlights

► Ovarian cancer patients have a high prevalence of sleep disturbances and poor sleep quality.
► Sleep disturbances are associated with decreased quality of life and increased depression.

Platinum Sensitivity–Related Germline Polymorphism Discovered via a Cell-Based Approach and Analysis of Its Association with Outcome in Ovarian Cancer Patients

Conclusion:
This study shows the potential of cell-based, genome-wide approaches to identify germline predictors of treatment outcome and highlights the need for extensive validation in patients to assess their clinical effect.

full free access: Survival of patients with ovarian cancer in central and northern Denmark, 1998–2009

Objective

To examine time trends of survival and mortality of ovarian cancer in the central and northern Denmark regions during the period 1998–2009.

Conclusion

The survival of ovarian cancer patients did not improve during the study period. This lack of improvement contrasts with the national cancer strategies implemented during this last decade, focusing on improving the survival of ovarian cancer patients.

abstract: The impact of pretreatment thrombocytosis and persistent thrombocytosis after adjuvant chemotherapy in patients with advanced epithelial ovarian cancer.

OBJECTIVE:

To evaluate the impact of both pretreatment thrombocytosis, and platelet count reduction post-adjuvant chemotherapy, on survival in patients with advanced epithelial ovarian cancer.

METHODS:

Records of 179 women who underwent cytoreductive surgery for FIGO stage III or IV epithelial ovarian cancer and received six cycles of platinum/paclitaxel-based chemotherapy between July1998 and March 2009 were retrospectively reviewed.....

RESULTS:

Sixty-two of 179 (34.6%) patients had thrombocytosis at primary diagnosis. Patients with preoperative thrombocytosis had greater elevations of CA-125 (p<0.0001) and a greater volume of ascites (p=0.007). On multivariate analysis, thrombocytosis and CA-125 elevation retained significance as indicators of poor prognosis in patients with stage III or IV disease. In patients with normal CA-125 after chemotherapy, a high platelet ratio was an independent risk factor for reduced survival (p=0.05).

CONCLUSIONS:

Preoperative thrombocytosis and a high platelet ratio appear to be poor prognostic factors of survival in patients with advanced epithelial ovarian cancer who were treated with cytoreductive surgery and adjuvant platinum/paclitaxel-based chemotherapy

abstract: Ovarian cancer in the elderly: Impact of surgery on morbidity and survival (France)

Note: in this study 'elderly' =  70+ yrs

CONCLUSION:

Elderly ovarian cancer patients undergo less extensive surgery and have lower OS (overall survival) despite similar postoperative morbidity, optimal resection and DFS. OS decrease could be explained by difference in the management of recurrences.