Bunja Rungruang

Does Aggressive Surgery Improve Outcomes? Interaction Between Preoperative Disease Burden and Complex Surgery in Patients With Advanced-Stage Ovarian Cancer: An Analysis of GOG 182

PURPOSE To examine the effects of disease burden, complex surgery, and residual disease (RD) status on progression-free (PFS) and overall survival (OS) in patients with advanced epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC) and complete surgical resection (R0) or < 1 cm of RD (MR) after surgical cytoreduction. PATIENTS AND METHODS Demographic, pathologic, surgical, and outcome data were collected from 2,655 patients with EOC or PPC enrolled onto the Gynecologic Oncology Group 182 study. The effects of disease distribution (disease score [DS]) and complexity of surgery (complexity score [CS]) on PFS and OS were assessed using the Kaplan-Meier method and multivariable regression analysis. RESULTS Consistent with existing literature, patients with MR had worse prognosis than R0 patients (PFS, 15 v 29 months; P < .01; OS, 41 v 77 months; P < .01). Patients with the highest preoperative disease burden (DS high) had shorter PFS (15 v 23 or 34 months; P < .01) and OS (40 v 71 or 86 months; P < .01) compared with those with DS moderate or low, respectively. This relationship was maintained in the subset of R0 patients with PFS (18.3 v 33.2 months; DS moderate or low: P < .001) and OS (50.1 v 82.8 months; DS moderate or low: P < .001). After controlling for DS, RD, an interaction term for DS/CS, performance status, age, and cell type, CS was not an independent predictor of either PFS or OS. CONCLUSION In this large multi-institutional sample, initial disease burden remained a significant prognostic indicator despite R0. Complex surgery does not seem to affect survival when accounting for other confounding influences, particularly RD.

Upper abdominal procedures in advanced stage ovarian or primary peritoneal carcinoma patients with minimal or no gross residual disease: An analysis of Gynecologic Oncology Group (GOG) 182

PURPOSE To examine the utility of upper abdominal procedures (UAPs) performed in a cohort of optimally cytoreduced patients with advanced stage epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC) and identify potential areas where aggressive surgery may impact survival. PATIENTS AND METHODS We reviewed 2655 patients enrolled in Gynecologic Oncology Group (GOG) 182 who had complete resection (CR) or minimal residual (MR) disease <1cm. Demographic, pathologic, surgical, and outcome data were collected. UAPs included diaphragm stripping or resection, liver resection, splenectomy, pancreatectomy, and porta hepatis surgery. Effect of UAP and CR on PFS/OS was assessed by Kaplan-Meier and proportional hazards methods. RESULTS Four-hundred eighty-two patients (18.1%) underwent a total of 590 UAPs. There were 351 (13.1%) diaphragm surgeries, 112 (4.2%) liver surgeries, 108 (4%) splenectomies, 12 (0.5%) pancreatectomies, and 7 (0.2%) porta hepatis surgeries. Comparing patients who did not have UAPs to patients who had UAPs, the PFS was 18.2 months (mos) and 14.8 mos (p < 0.01) and OS was 49.8 mos v. 43.7 mos (p = 0.01), respectively. However, in the multivariable analysis this survival benefit did not remain (PFS HR = 1.03, 95% CI 0.91-1.15; OS HR=0.92, 95%CI 0.81-1.04). The OS of the 141 patients who had an UAP and achieved CR compared to the 341 patients who had an UAP with MR was 54.6 compared to 40.4 mos (p=0.0005). CONCLUSIONS UAP procedures should only be performed when CR is attainable. A significant proportion of patients with MR were left with diaphragmatic disease that could potentially be completely resected.

Surgery versus radiation therapy for stage IB2 cervical carcinoma: a population-based analysis.

Objective The objective of the study was to examine outcomes in stage IB2 cervical cancer patients undergoing primary surgery versus radiation. Methods Stage IB2 cervical cancer patients were identified from the Surveillance, Epidemiology and End Results Public-Use Database from 2000 to 2006. Patients were divided into those receiving radiation (radiation first) or surgery (surgery first) as initial treatment. Overall survival was calculated by Kaplan-Meier method and compared using log-rank test. Results In total, 770 patients were identified with stage IB2 cervical cancer; 369 received radiation, and 401 received surgery initially. The radiation-first group had larger mean tumor size than the surgery-first group (6.0 vs 5.5 cm, respectively; P < 0.0001). The overall survival was longer in the surgery-first group compared with the radiation-first group (72.0 vs 61.4 months, respectively; P < 0.0001). Conclusions Patients undergoing surgery as initial treatment for stage IB2 cervical cancer appear to have improved outcomes in the current era of chemoradiation; however, given the lack of chemotherapy information, a randomized trial will be necessary to see if these results remain valid.

Assessment of buffer systems for harvesting proteins from tissue interstitial fluid for proteomic analysis.

Tissue interstitial fluid (TIF) bathes cells in tissues, and it is hypothesized that TIF proximal to a developing tumor may contain an enriched population of tumor-specific shed and secreted proteins relative to peripheral blood. Extraction of TIF proteins is typically accomplished through passive incubation of surgically resected tissues in phosphate buffered saline (PBS); however, its influence on cellular activity and viability has not been fully explored. The present investigation sought to characterize whether different buffer systems influence the recovered TIF proteome. Five TIF buffer systems were investigated including PBS, Dulbeccos modified Eagle medium (DMEM), and three organ transplantation preservative solutions: Celsior solution S (CS), histidine-tryptophan-ketoglutarate (HTK), and University of Wisconsin (UW). Kidney tumor, adjacent normal kidney, and ovarian tumor tissues were incubated in each of the buffer systems, and the harvested TIF proteins were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Although the present results indicate that no significant differences exist in the recovered proteins from these two neoplasms between the five solution groups, additional sample preparative steps are required prior to LC-MS/MS for TIF proteins harvested from DMEM, UW, CS, and HTK. These data support that PBS is a suitable and convenient solution for harvesting TIF proteins for MS-based proteomics.

Novel surgical approaches for sampling the ovarian surface epithelium and proximal fluid proteome.

The pathogenesis of ovarian, fallopian tube, and peritoneal cancers has been difficult to elucidate despite intense effort. Recently, though, the care of women felt to be at high risk due to a strong family history of breast and/or ovarian cancer or a known germline BRCA1 or BRCA2 mutation has provided potential insight into the development of these malignancies. Risk-reducing surgical removal of the fallopian tubes and ovaries, called risk-reducing bilateral salpingo-oopherectomy (RRBSO), is commonly performed as a laparoscopic procedure to minimize recovery time. We describe here an optimized surgical sampling workflow for analyzing the proteomes of peritoneal, fallopian tube, and ovarian surface epithelial (OSE) specimens collected at the time of laparoscopic RRBSO, a technique which has not been described previously. This methodology presents a unique opportunity for closer examination of the proteomic alterations in the tissues at risk for malignant transformation in women with an inherited susceptibility to ovarian, fallopian tube, and peritoneal cancer development.

The risk of subsequent malignancies in women with uterine papillary serous or clear cell endometrial cancers.

Objective Type II endometrial cancers include uterine papillary serous carcinoma (UPSC) and clear cell endometrial cancer (CC). Given their relative rarity, aggressive nature, and poor prognosis, little is known about the risk of subsequent malignancies at other sites. Our objective was to determine if women with UPSC or CC are at increased risk of subsequent malignancies. Type II endometrial cancers include uterine papillary serous carcinoma (UPSC) and clear cell endometrial cancer (CC). Given their relative rarity, aggressive nature, and poor prognosis, little is known about the risk of subsequent malignancies at other sites. Our objective was to determine if women with UPSC or CC are at increased risk of subsequent malignancies. Methods Women diagnosed with UPSC or CC were identified from the SEER (Surveillance Epidemiology and End Results) Program from 1973 to 2005. Cases with a second gynecologic malignancy were excluded. Using SEER*Stat software, standardized incidence ratios (SIRs) of subsequent malignancies were calculated. Results A total of 8045 and 1740 patients were diagnosed with UPSC and CC, respectively. Four hundred sixty-one (5.7%) of the UPSC cases were diagnosed with at least 1 additional nongynecologic malignancy. Significant associations were found with the following malignancies: the renal pelvis, soft-tissue sarcomas, acute myeloid leukemia, the bladder, and colon. Seventy-eight CC cases (4.5%) were diagnosed with at least 1 additional malignancy. In comparison with the baseline population risk, there was no statistically significant increased risk of any subsequent malignancy with a primary diagnosis of CC. Conclusions This is the first large population-based analysis of second primary malignancies after type II endometrial cancers. Uterine papillary serous carcinoma is associated with increased risks of certain subsequent malignancies, and providers should be aware of these when following up patients with this diagnosis, especially those with stage I disease. In contrast, no such associations were found with CC in this cohort.

Clinicopathologic characteristics associated with long-term survival in advanced epithelial ovarian cancer: an NRG Oncology/Gynecologic Oncology Group ancillary data study ☆ ☆☆ ★

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.

What is the role of retroperitoneal exploration in optimally debulked stage IIIC epithelial ovarian cancer? An NRG Oncology/Gynecologic Oncology Group ancillary data study

The purpose of this study was to determine the effect of retroperitoneal (RP) exploration on progression‐free survival (PFS) and overall survival (OS) in epithelial ovarian cancer (EOC) patients with stage IIIC disease who underwent optimal debulking surgery.

Multiplex glycan bead array for high throughput and high content analyses of glycan binding proteins

Glycan-binding proteins (GBPs) play critical roles in diverse cellular functions such as cell adhesion, signal transduction and immune response. Studies of the interaction between GBPs and glycans have been hampered by the availability of high throughput and high-content technologies. Here we report multiplex glycan bead array (MGBA) that allows simultaneous analyses of 384 samples and up to 500 glycans in a single assay. The specificity, sensitivity and reproducibility of MGBA are evaluated using 39 plant lectins, 13 recombinant anti-glycan antibodies, and mammalian GBPs. We demonstrate the utility of this platform by the analyses of natural anti-glycan IgM and IgG antibodies in 961 human serum samples and the discovery of anti-glycan antibody biomarkers for ovarian cancer. Our data indicate that the MGBA platform is particularly suited for large population-based studies that require the analyses of large numbers of samples and glycans.The low throughput or content of current methods for the analysis of glycans-glycan binding proteins (GBPs) interactions hampers their clinical applications. Here, the authors conjugate synthesized glycans to Luminex beads to detect GBPs and apply it for the discovery of ovarian cancer biomarkers.

Benign breast diseases: epidemiology, evaluation, and management.

Benign breast diseases are common and encompass a spectrum of disorders. The majority of diagnoses will stem from a patient presenting with symptoms such as a mass or discomfort, or as a result of breast imaging which shows abnormalities leading to percutaneous biopsy. When mammographic and pathologic findings are disconcordant or when a high-risk lesion that can be associated with a preinvasive or invasive malignancy is found, formal excisional biopsy is recommended.