ABSTRACT
OBJECTIVE: To identify clinicopathologic factors associated with 10-year overall survival in epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC), and to develop a predictive model identifying long-term survivors. METHODS: Demographic, surgical, and clinicopathologic data were abstracted from GOG 182 records. The association between clinical variables and long-term survival (LTS) (>10years) was assessed using multivariable regression analysis. Bootstrap methods were used to develop predictive models from known prognostic clinical factors and predictive accuracy was quantified using optimism-adjusted area under the receiver operating characteristic curve (AUC). RESULTS: The analysis dataset included 3010 evaluable patients, of whom 195 survived greater than ten years. These patients were more likely to have better performance status, endometrioid histology, stage III (rather than stage IV) disease, absence of ascites, less extensive preoperative disease distribution, microscopic disease residual following cyoreduction (R0), and decreased complexity of surgery (p<0.01). Multivariable regression analysis revealed that lower CA-125 levels, absence of ascites, stage, and R0 were significant independent predictors of LTS. A predictive model created using these variables had an AUC=0.729, which outperformed any of the individual predictors. CONCLUSIONS: The absence of ascites, a low CA-125, stage, and R0 at the time of cytoreduction are factors associated with LTS when controlling for other confounders. An extensively annotated clinicopathologic prediction model for LTS fell short of clinical utility suggesting that prognostic molecular profiles are needed to better predict which patients are likely to be long-term survivors.
Subject(s)
Neoplasms, Glandular and Epithelial/mortality , Ovarian Neoplasms/mortality , Peritoneal Neoplasms/mortality , Aged , Ascites/mortality , Ascites/pathology , CA-125 Antigen/metabolism , Carcinoma, Ovarian Epithelial , Female , Humans , Middle Aged , Neoplasm, Residual , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/pathology , Peritoneal Neoplasms/pathology , ROC Curve , United States/epidemiologyABSTRACT
OBJECTIVE: Natural killer (NK) cells represent a powerful immunotherapeutic target as they lyse tumors directly, do not require differentiation, and can elicit potent inflammatory responses. The objective of these studies was to use an IL-15 super-agonist complex, ALT-803 (Altor BioScience Corporation), to enhance the function of both normal and ovarian cancer patient derived NK cells by increasing cytotoxicity and cytokine production. METHODS: NK cell function from normal donor peripheral blood mononuclear cells (PBMCs) and ovarian cancer patient ascites was assessed using flow cytometry and chromium release assays ±ALT-803 stimulation. To evaluate the ability of ALT-803 to enhance NK cell function in vivo against ovarian cancer, we used a MA148-luc ovarian cancer NOD scid gamma (NSG) xenogeneic mouse model with transferred human NK cells. RESULTS: ALT-803 potently enhanced functionality of NK cells against all ovarian cancer cell lines with significant increases seen in CD107a, IFNγ and TNFα expression depending on target cell line. Function was also rescued in NK cells derived from ovarian cancer patient ascites. Finally, only animals treated with intraperitoneal ALT-803 displayed an NK dependent significant decrease in tumor. CONCLUSIONS: ALT-803 enhances NK cell cytotoxicity against ovarian cancer in vitro and in vivo and is able to rescue functionality of NK cells derived from ovarian cancer patient ascites. These findings suggest that ALT-803 has the potential to enhance NK cell-based immunotherapeutic approaches for the treatment of ovarian cancer.
Subject(s)
Interleukin-15/agonists , Killer Cells, Natural/drug effects , Killer Cells, Natural/immunology , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/immunology , Proteins/pharmacology , Animals , Ascites/immunology , Ascites/pathology , Female , Humans , K562 Cells , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/immunology , Lymphocyte Activation/drug effects , Mice , Mice, Inbred NOD , Mice, SCID , Recombinant Fusion Proteins , Xenograft Model Antitumor AssaysABSTRACT
BACKGROUND: With the pharmacokinetic advantages of intraperitoneal chemotherapy delivery and the increased popularity of immunotherapy and gene therapy, intraperitoneal catheters have moved to the forefront as a delivery system in cancer treatment. This delivery system, however, carries with it an intrinsic morbidity warranting attention in the often prolonged chemotherapy regimens demanded by cancer patients. CASE: In reviewing the literature of intraperitoneal catheter complications, there is no other cited case of a peritoneal catheter erosion into intestine presenting as an enterovaginal fistula. Our patient, diagnosed with persistent ovarian carcinoma, had a peritoneal Tenckoff catheter placed for chemotherapy. Many months after termination of the chemotherapy and 15 months after placement, she presented with bowel contents per vagina. A CT scan revealed an abdominopelvic abscess encompassing the detached catheter which embedded in the rectosigmoid colon, allowing direct communication to the upper vagina. The catheter was removed and the abscess was drained. CONCLUSION: Intraperitoneal catheters have a morbidity that persists after nonuse. Therefore, intraperitoneal catheters should be removed if they are not being used.
