Recurrence-free Survival Hazard Ratio Research Articles

Prognostic Significance of p21-activated Kinase 6 Expression in Patients with Clear Cell Renal Cell Carcinoma

To investigate prognostic values of intratumoral p21-activated kinase 6 (PAK6) expression in patients with clear cell renal cell carcinoma (ccRCC). Immunohistochemistry in tissue microarray was used to evaluate the expression of PAK6 in 104 patients who had undergone nephrectomy at Zhongshan Hospital of Fudan University. Prognostic value and clinical outcomes were evaluated. Intratumoral PAK6 expression was significantly lower than nontumoral tissues (P < 0.001). Moreover, low expression of PAK6 was associated with unfavorable overall survival (OS) (P = 0.001) and recurrence-free survival (RFS) (P = 0.001). In the subgroup of patients with tumor, node, metastasis classification system (TNM) stage I + II disease, those with low expression of PAK6 were prone to have poor OS (P = 0.014) and RFS (P = 0.037). Intratumoral PAK6 low expression was correlated with tumor size (P = 0.001) and TNM stage (P = 0.006), and was identified as an independent prognostic factor for OS (hazard ratio 4.109, P = 0.002) and RFS (hazard ratio 3.175, P = 0.002). Use of an extended TNM staging system with intratumoral PAK6 expression showed a better prognostic value for OS [area under the receiver operating characteristic curve (AUC) 0.790, P = 0.022] and RFS (AUC 0.769, P = 0.040). The c-index of a Cox-based model combined with Eastern Cooperative Oncology Group performance status, TNM stage, Fuhrman grade, and PAK6 was 0.83 for OS and 0.80 for RFS. Intratumoral PAK6 could be a potential prognosticator for OS and RFS in ccRCC patients after nephrectomy. Further external validation and functional analysis should be pursued to assess its potential prognostic and therapeutic values for ccRCC patients.

Perioperative beta-blocker use and survival in lung cancer patients

Study ObjectiveTo assess the effect of perioperative beta blockers on recurrence and overall survival after non-small cell lung cancer surgery. DesignRetrospective study. SettingAcademic medical center. MeasurementsThe medical records of patients with stage 1, 2, and 3a non-small cell lung cancer were divided into three different groups: those patients who never received beta blockers perioperatively, those receiving nonselective beta blockers within 60 days of surgery, and those taking selective beta blockers within 60 days of surgery.Recurrence-free survival and overall survival were the main clinical endpoints. Univariate log-rank tests and multivariate Cox proportional hazards models were used to assess the effects of selective beta blockers, nonselective beta blockers, or no beta blockers on recurrence-free survival and overall survival. Main ResultsThe analysis included records of 435 patients. Univariate analyses showed that the use of both selective and nonselective beta blockers was associated with decreased recurrence-free survival (P = 0.014) and overall survival (P = 0.009). However, these findings were not sustained after adjusting for possible confounding variables in the multivariate analysis. The hazard ratios for recurrence-free survival (selective beta blockers vs no beta blocker use were: 1.304; 95% confidence intervals [CI] 0.973 - 1.747; P = 0.075; for nonselective beta blockers vs no beta blockers: 0.989; 95% CI 0.639 - 1.532; P = 0.962. The hazard ratios for overall survival were: selective beta blocker use vs no beta blockers: 1.335; 95% CI 0.966 - 1.846; P = 0.080; nonselective beta blocker use vs no beta blocker use: 1.108; 95% CI 0.678 - 1.812; P = 0.682. ConclusionAdministration of beta blockers during the perioperative period did not improve recurrence-free or overall survival in patients undergoing resection of non-small cell lung cancer.

Obesity, diabetes, and survival outcomes in a large cohort of early-stage breast cancer patients

BackgroundTo determine the relationship between obesity, diabetes, and survival in a large cohort of breast cancer patients receiving modern chemotherapy and endocrine therapy. Patients and methodsWe identified 6342 patients with stage I–III breast cancer treated between 1996 and 2005. Patients were evaluated according to body mass index (BMI) category and diabetes status. ResultsIn a multivariate model adjusted for body mass index, diabetes, medical comorbidities, patient- and tumor-related variables, and adjuvant therapies, relative to the normal weight, hazard ratios (HRs) for recurrence-free survival (RFS), overall survival (OS), and breast cancer-specific survival (BCSS) for the overweight were 1.18 [95% confidence interval (CI) 1.02–1.36], 1.20 (95% CI 1.00–1.42), and 1.21 (95% CI 0.98–1.48), respectively. HRs for RFS, OS, and BCSS for the obese were 1.13 (95% CI 0.98–1.31), 1.24 (95% CI 1.04–1.48), and 1.23 (95% CI 1.00–1.52), respectively. Subset analyses showed these differences were significant for the ER-positive, but not ER-negative or HER2-positive, groups. Relative to nondiabetics, HRs for diabetics for RFS, OS, and BCSS were 1.21 (95% CI 0.98–1.49), 1.39 (95% CI 1.10–1.77), and 1.04 (95% CI 0.75–1.45), respectively. ConclusionsIn patients receiving modern adjuvant therapies, obesity has a negative impact on RFS, OS, and BCSS; and diabetes has a negative impact on RFS and OS. Control of both may be important to improving survival in obese and diabetic breast cancer patients.

Phase 2 Study of Erlotinib Combined With Adjuvant Chemoradiation and Chemotherapy in Patients With Resectable Pancreatic Cancer

Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20% for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine-erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC. Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m(2) twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m(2) on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS). The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85% of patients, and margins were positive in 17%. The median RFS was 15.6 months (95% confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95% CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31%/2% and 35%/8%, respectively. Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer.

Relationship between epithelial and stromal TRIM28 expression predicts survival in colorectal cancer patients

TRIM28 is a multi-domain nuclear protein with pleotropic effects in both normal and tumor cells. In this study, TRIM28 expression in epithelial and stromal tumor microenvironment and its prognostic role in colorectal cancer were investigated. Immunohistological staining of TRIM28 was evaluated in tissue microarrays constructed from 137 colorectal cancer patients. The correlations of TRIM28 expression with clinicopathological features and p53 expression were studied. Kaplan-Meier analysis and Cox proportional hazard modeling were used to assess overall survival (OS) and recurrence-free survival (RFS). Strong epithelial TRIM28 expression was found in 42% of colorectal cancer tissues. TRIM28 expression correlated significantly with p53 expression in matched cases (P=0.0168, Spearman rank test). A high epithelial to stromal TRIM28 expression ratio was associated with shorter OS (P=0.033; log-rank test) and RFS (P=0.043; log-rank test). Multivariate analysis showed that the epithelial to stromal TRIM28 expression ratio was an independent predictor of OS (hazard ratio=2.136; 95% confidence interval 1.015-4.498, P=0.046) and RFS (hazard ratio=2.100; confidence interval 1.052-4.191, P=0.035). A high TRIM28 expression ratio between stromal and epithelial compartments in colorectal cancer tissue is an independent predictor of poor prognosis. The pathophysiological role of TRIM28 in carcinogenesis may be dependent on expression levels and cell type within the tumor microenvironment.

Survival Outcomes of Breast Cancer Patients Who Receive Neoadjuvant Chemotherapy: Association with Dynamic Contrast-enhanced MR Imaging with Computer-aided Evaluation

To retrospectively evaluate whether dynamic contrast agent-enhanced (DCE) magnetic resonance (MR) imaging parameters assessed by a computer-aided evaluation program are associated with recurrence-free and overall survival in breast cancer patients who received neoadjuvant chemotherapy (NAC). This study was institutional review board approved and informed consent was waived. Between January 2007 and December 2009, 187 consecutive women (mean age, 46.6 years; range, 24-78 years) who had undergone NAC, DCE MR imaging before and after NAC, and surgery for invasive breast cancers (mean size, 5.0 cm; range, 2.0-14.8 cm on surgical histologic analysis) were identified. The tumor size, volume, and kinetic parameters (persistent, plateau, or washout components) were measured with a computer-aided evaluation program on DCE MR images before and after NAC, and their percentage changes were calculated. The Cox proportional hazards model was used to determine the association between DCE MR imaging parameters and recurrence-free survival and overall survival after controlling for clinical-pathologic variables. There were 50 events, including 38 recurrences (29 distant, six local, and three both) and 12 deaths, at a mean follow-up of 47.4 months. At multivariate analysis, a smaller reduction in tumor volume (recurrence-free survival hazard ratio, 5.75; 95% confidence interval: 1.14, 8.64; and overall survival hazard ratio, 2.12; 95% confidence interval: 1.08, 5.69) and a smaller reduction in washout component (recurrence-free survival hazard ratio, 1.15; 95% CI: 1.06, 1.55; and overall survival hazard ratio, 1.26; 95% confidence interval: 1.03, 1.52) after NAC were independent significant variables for worse recurrence-free survival and overall survival. Smaller reduction in tumor volume and a smaller reduction in washout component on DCE MR images assessed with computer-aided evaluation after NAC were independent parameters of worse recurrence-free survival and overall survival in breast cancer patients who received NAC.

Synergistic Effect of Bcl-2 and Cyclin A2 on Adverse Recurrence-Free Survival in Stage I Non-small Cell Lung Cancer

The prognostic significance of cyclin A2 overexpression in non-small cell lung cancer (NSCLC) is controversial. To understand the effect of cyclin A2 on recurrence in NSCLC, we retrospectively analyzed the expression of Bcl-2, cyclin A2, E-cadherin, Ki-67, and p53 using immunohistochemistry in 635 NSCLCs. Overexpression of cyclin A2 was found in 466 (73%) of 635 NSCLCs, and recurrence occurred in 291 (46%) of 635 NSCLCs with a median follow-up of 5.4 years. The relationship between recurrence and cyclin A2 overexpression was not homogenous by pathologic stage (Breslow-Day test for homogeneity, P = 0.007). Overexpression of cyclin A2 was associated with poor recurrence-free survival (RFS) in 374 stage I NSCLCs (P = 0.02), and RFS was worse in patient with negative expression of Bcl-2 than those with positive expression of Bcl-2. Cox proportional hazard analysis showed that stage I NSCLC patients with overexpression of cyclin A2 and negative expression of Bcl-2 had poorer RFS (hazard ratio = 3.86, 95% confidence interval = 1.07-15.77; P = 0.03) than those with normal expression of cyclin A2 and Bcl-2, after adjusting for age, adjuvant radiotherapy, and histology. Neural network and generalized linear model including cyclin A2 and Bcl-2 showed best performance in the prediction of recurrence; error rates for neural network and generalized linear model were 15% and 12%, respectively. Negative effect of cyclin A2 on RFS in stage I NSCLC was aggravated by negative expression of Bcl-2.

Type II papillary histology predicts poor outcome in patients with renal cell carcinoma and vena cava thrombus

What's known on the subject? and What does the study add? In patients with pRCC, the presence of venous tumour thrombus is known to be a predictor of poorer outcomes. However, a paucity of data is available regarding the prognostic significance of histology in patients with RCC and IVC thrombus. In our series, we found that patients with type II pRCC had significantly poorer outcomes when compared to those with cRCC. Although the lack of effective treatment for patients with metastatic pRCC may have contributed to these adverse outcomes, type II papillary histology was independent predictor not only of CSS but also of RFS. • To analyze the prognostic impact of papillary histology on oncological outcomes in patients with renal cell carcinoma (RCC) and inferior vena cava (IVC) thrombus. • We reviewed the medical records of 74 patients who underwent radical nephrectomy and IVC thrombectomy between 1990 and 2010 for clear cell or papillary RCC. • We compared the clinicopathological features and clinical outcomes of 62 patients with clear cell RCC (cRCC) and 12 with papillary RCC (pRCC). • All cases of pRCC were subdivided into type I or type II. • The prognostic role of papillary histology on recurrence-free survival (RFS) and cancer-specific survival (CSS) was estimated using Cox's regression models. • Upon reclassification of the pRCC subtype, all 12 patients with pRCC had type II tumours. • Patients with type II pRCC were significantly younger (P=0.028) and were more probably women (P=0.025) than those with cRCC • The 2- and 5-year CSS rates were 81.1% and 53.6% in cRCC patients, and 28.1% and 0% in type II pRCC patients, respectively. All eight patients with non-metastatic type II pRCC developed disease recurrence at a median interval of 6 months after surgery, whereas 25 of 44 (56.8%) patients with non-metastatic cRCC experienced such recurrence at a median interval of 10 months after surgery. • Patients with type II pRCC showed significantly lower CSS (P<0.001) and RFS (P=0.002) than those with cRCC. • On multivariate analysis, type II papillary histology was an independent predictor of CSS (hazard ratio, 3.73; P=0.003) and RFS (hazard ratio, 3.15; P=0.015). • Type II papillary histology appears to be predominant in cases of pRCC with IVC thrombus. • Patients with type II pRCC who presented with IVC thrombus had significantly worse outcomes than those with cRCC, and histology is an important prognostic factor in patients with RCC and IVC thrombus.

Impact of tumour location versus multifocality in patients with upper tract urothelial carcinoma treated with nephroureterectomy and bladder cuff excision: a homogeneous series without perioperative chemotherapy

It is well established that upper tract urothelial carcinoma is a rare cancer with an aggressive course. Currently, radical nephroureterectomy with bladder cuff excision remains the standard of care in the treatment of these tumours. Previous studies demonstrate that stage, grade and lymphovascular invasion have prognostic significance on recurrence and outcome whereas the prognostic impact of tumour location remains unclear. This study provides an accurate analysis of the impact of tumour location and multifocality on prognosis in patients with upper tract urothelial carcinoma following nephroureterectomy with bladder cuff excision. Ureteral tumour location, particularly when associated with multifocal disease in the renal pelvis, is significantly associated with an increased risk of disease recurrence and cancer-specific death after surgery. To examine the significance of ureteral and renal pelvic location of upper tract urothelial carcinoma in a large multi-institutional study. We collected and pooled a database of 637 patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy and bladder cuff excision in nine international academic centres. Univariate and multivariate models examined the effect of tumour location on recurrence-free survival (RFS) and cancer-specific survival (CSS) rates. Collected variables included age, gender, race, presence of lymphovascular invasion, concomitant carcinoma in situ, pathological stage, lymph node dissection and type of surgery (open vs laparoscopic). Anatomically, 34% of tumours were ureteral, 59% were renal pelvic and 7% were multifocal. Median follow-up for patients alive was 42 months (interquartile range: 19-76). Race, type of surgery, pathological stage and presence of lymphovascular invasion were significantly different across the three subgroups of patients (all P values <0.05). Age, gender, grade, presence of concomitant carcinoma in situ and follow-up duration were similar among the three subgroups. On multivariable Cox regression analyses, ureteral tumour location was an independent predictor of worse RFS (hazard ratio 2.1, P = 0.006) and CSS (hazard ratio 2.0, P = 0.027). When associated with renal pelvic disease, ureteral location was an even stronger independent predictor of worse RFS (hazard ratio 4.6, P < 0.001) and CSS (hazard ratio 4.0, P < 0.001). Ureteral tumour location, particularly in association with multifocal disease in the renal pelvis, is an independent prognostic factor for higher disease recurrence and cancer-specific mortality.

The Effects of Anesthetic Technique on Cancer Recurrence in Percutaneous Radiofrequency Ablation of Small Hepatocellular Carcinoma

Retrospective studies report that the benefit of regional anesthesia on cancer recurrence may depend on the specific tumor type. We compared the association between anesthetic technique and cancer recurrence in patients undergoing percutaneous radiofrequency ablation (RFA) of small hepatocellular carcinoma (HCC). We retrospectively reviewed medical records of patients with small HCC treated with RFA between August 1999 and December 2008. Patients receiving epidural anesthesia were compared with a group given general anesthesia. The end points were recurrence-free survival and overall survival, which were assessed using the Kaplan-Meier technique and compared using a multivariate Cox proportional hazards regression model and an alternative model with inverse probability weights to adjust for propensity score. The hazard ratio for recurrence-free survival in the epidural anesthesia group compared with the general anesthesia group was 3.66 (95% confidence interval [CI], 2.59-5.15; P < 0.001) in the Cox regression model and 4.31 (95% CI, 2.24-8.29; P < 0.001) in the analysis adjusted for propensity score with inverse probability weights. The hazard ratio for overall survival in the epidural anesthesia group compared with the general anesthesia group was 0.77 (95% CI, 0.50-1.18; P = 0.232) in the Cox regression model and 1.26 (95% CI, 0.81-1.97; P = 0.312) in the analysis adjusted for propensity score with inverse probability weights. This retrospective analysis suggests that treatment of small HCC by RFA under general anesthesia is associated with reduced risk of cancer recurrence. No effect of anesthetic technique on overall survival is detected. Prospective, randomized trials to evaluate this association are warranted.

Improving the clinical risk score: An analysis of molecular biomarkers in the era of modern chemotherapy for resectable hepatic colorectal cancer metastases

The prognostic relevance of variations in expression of specific tumor genes in colorectal cancer liver metastases (CRCLMs) in patients treated with resection and modern chemotherapy is not known. Patients submitted to liver resection for CRCLM between January 2000 and October 2007 were studied. A clinical risk score (CRS; range, 0-5) was calculated for each patient. RNA was extracted from histologically confirmed tumor isolates, and using real-time polymerase chain reaction (PCR) studies, we assessed the quantitative expression of 12 genes with potential importance in chemotherapy resistance and tumor progression, including thymidylate synthase (TS; 5-fluorouracil), excision repair cross complementing gene-1, and xeroderma pigmentosum groups A through G (oxaliplatin), topoisomerase-I (irinotecan), c-met, and hepatocyte growth factor. Primary outcomes were recurrence-free survival (RFS) and disease-specific survival (DSS) after hepatic resection. One-hundred fifty-five patients with good quality tumor mRNA were identified. Median follow-up was 32 months for survivors, and the median CRS was 2. Eighty-seven patients (56%) received preoperative chemotherapy, and 124 (80%) received postoperative chemotherapy. Median RFS for all patients was 13 months, and 3-year DSS was 69%. Median RFS and 3-year DSS for patients with an increased CRS (3-5) was lower (7 vs 18 months [P < .0001] and 50% vs. 80% [P < .0001], respectively). Of the 12 genes studied, only increased TS expression was associated with a lower RFS (hazard ratio, 1.16; 95% confidence interval, 1.0-1.3; P = .03) and DSS (hazard ratio, 1.25; 95% confidence interval, 1.0-1.5; P = .03). Median RFS and 3-year DSS for patients with increased TS expression was decreased (9 vs. 15 months [P = .03] and 48% vs. 82% [P = .001], respectively). TS expression had prognostic value that was independent of CRS on multivariate analysis. In patients with hepatic CRCLM treated with resection and modern chemotherapy, increased expression of TS improves outcome stratification and appears to be a useful biomarker.

Outcomes of Temporal Bone Resection for Locally Advanced Parotid Cancer

This study was conducted to report outcomes and identify factors predictive of survival and recurrence in patients undergoing lateral temporal bone resection (LTBR) as part of an extended radical parotidectomy for parotid cancer. This is a retrospective cohort study which includes all patients undergoing LTBR for parotid cancer between 1994 and 2010 at two affiliated academic centers. Survival and recurrence rates were analyzed using the Kaplan-Meier method and Cox multivariate regression. A total of 12 patients with median follow-up duration of 30.6 months were included: 6 de novo cases and 6 patients referred after local recurrence. Actuarial locoregional control at 2 years was 73%. Most patients (11; 92%) developed disease recurrence with distant metastases the most common site of first failure (83%). Overall and disease-specific survival rates were 80% at 2 years and 22.5% at 5 years. Recurrence-free survival (RFS) was 67% at 2 years and 8.3% at 5 years. On multivariate analysis, surgical margin status was an independent predictor of RFS (hazard ratio = 3.85, p = 0.045). In advanced parotid cancer, LTBR with a goal of gross total resection offers good locoregional control with an acceptable complication rate. The benefits of this surgery must be balanced with the morbidity and low likelihood of long-term survival, with most patients ultimately experiencing disease recurrence and death.

High-grade transformation in acinic cell carcinoma of the salivary glands: A rare but important clinical entity.

5581 Background: The phenomenon of high-grade transformation (HGT) has been described in select salivary gland malignancies. Previous studies of salivary gland HGT have noted a propensity for recurrent disease, lymph node (LN) metastases, and poor overall survival (OS). We report the clinical and pathologic findings in cases of acinic cell carcinoma (AcCC) with HGT (AcCC-HGT). Methods: A retrospective clinical and histopathologic review was performed on 62 patients (pts) with AcCC who had surgery at the Mayo Clinic from 1985-2010. Microscopic review was performed by two pathologists (JJG, WS). Cases of AcCC-HGT were characterized by cytomorphologic pleomorphism, elevated mitotic activity, infiltrative growth pattern, stromal desmoplasia, and necrosis. Immunohistochemical and histochemical stains were performed on cases of AcCC-HGT (AE1/AE3, Cam 5.2, p63, S100, Mib-1, PAS, and PAS-D). Results: AcCC-HGT was seen in 7 of 62 pts (11%). The median age was 53.5 years (range 15-84, 31 female) for pts with AcCC versus 69 years (range 56-68, 5 female) for pts with AcCC-HGT. Histologically, an abrupt transition from a low- or intermediate-grade component into a discrete high-grade component was typically seen. The areas of HGT exhibited elevated proliferation based on MIB-1 expression and significant loss of zymogen granules using PAS and PAS-D staining. Initial treatment for all pts was surgery; 7 AcCC and 3 AcCC-HGT pts also had adjuvant radiation. LNs were positive in 8% of AcCC pts (4/52, 3 unknown) at initial surgery compared with 43% of pts with AcCC-HGT (3/7). Known distant metastases developed in 2% of pts with AcCC (1/55) and 71% of pts with AcCC-HGT (5/7). Five-year recurrence free survival (RFS) was 82.7% for pts with AcCC and 19.0% for pts with AcCC-HGT (p<0.0001). Five-year OS was 93.5% for pts with AcCC and 40% for pts with AcCC-HGT (p<0.0001). Adjusting for age and gender, the hazard ratios for RFS and OS for pts with AcCC-HGT were 13.4 (95% CI, 3.6-50.1, p=0.0001) and 8.8 (95% CI, 2.1-35.5, p=0.0022). Conclusions: AcCC-HGT is a rare and aggressive salivary gland malignancy. The presence of HGT should be considered when determining indications for neck dissection, chemotherapy, and radiation.

Oncologic outcomes of partial versus radical nephrectomy for unilateral Wilms tumor.

9561 Background: According to the Children's Oncology Group (COG) and International Society of Pediatric Oncology (SIOP), the recommended surgical management for unilateral Wilms tumor (UWT) is radical nephrectomy (RN). However, recent data demonstrate that when oncologically feasible, renal preserving surgery decreases the likelihood of chronic renal disease and associated comorbidities. Thus, we analyzed outcomes of those undergoing partial nephrectomy (PN) compared to RN for UWT. Methods: We searched PubMed using: “Wilms tumor,” “Nephroblastoma,” “PN” and “Nephron Sparing Surgery.” Reviewing citations to eliminate repeat reports we found 115 patients who had PN for UWT. These reports were analyzed for: stage, recurrence, recurrence location, overall survival (OS) and time to event. 82 cases had adequate data to analyze. In comparison, the same endpoints were collected on all children who had RN for UWT from 1985-2010 at Childrens Med Ctr Dallas. Results: Of the 82 PN patients, 64 were stage I, 10 stage II, 6 stage III and 2 stage IV; however, this was a mix of patients staged/treated by SIOP or COG protocols. Of the 121 RN patients, 24 were stage I, 45 stage II, 29 stage III and 23 stage IV. All of these were treated by COG protocols. In the PN group, there were 9 total recurrences, 6 local recurrences and 4 deaths. At a median follow-up of 48mo (3-372), the recurrence free survival (RFS), local RFS and OS were 89.1%, 92.7% and 95.1% respectively. In the RN group, there were 20 total recurrences, 6 local recurrences and 6 deaths. At a median follow up of 69.3mo (0.1-214), the RFS, local RFS and OS were of 83.1%, 95.0% and 95.0% respectively. Using a Cox Regression Analysis to control for stage, there were no statistically significant differences in the above oncologic outcomes between the groups. The Hazard Ratio (HR) for the RN vs. PN group was: RFS HR=0.95 (95% CI 0.39-2.34), local RFS HR=0.77 (0.21-2.9) and OS HR=0.45 (0.17-4.39). Conclusions: Based on reported data, the oncologic outcomes of PN for UWT in a select population do not appear to differ from those of RN. With the potential for renal preservation and its associated benefits, PN for appropriately selected patients should be studied in a prospective, cooperative trial versus RN to definitively assess its role in UWT.

Biologic risk model for recurrence in resected early-stage non-small cell lung cancer (ES NSCLC).

7053 Background: Patients (pts) with resected ES NSCLC are at risk for recurrence of disease and mortality but we do not have tools to predict which pts are at highest risk. Risk models have been proposed but have not included predictive biomarkers for recurrence. Methods: We assembled a large comprehensive database with archival tissues and clinical follow-up from pts with resected ES NSCLC between 2002-2005. 21 biomarkers identified from our preclinical studies as related to pathogenesis of NSCLC were investigated, including pathways related to apoptosis, metabolism, DNA repair, inflammation and growth factors. Tissue microarrays were constructed from archived specimens. Cox models were fitted to estimate effects of clinical factors and biomarkers on recurrence free survival (RFS) and overall survival (OS). Predictive accuracy was quantified by C-index. Results: 370 pts are included in our analysis, 50.3% (186 pts) male, 89% (330) white. Smoking status: 44% (162) current, 46% (170) former, 10% (38) never. Stage IA 28% (103), IB 35% (131), II 20% (75), IIIA 17% (61). Adenocarcinoma 61% (227), squamous 34% (126). 45% (160) received chemotherapy or radiation as well as surgery. With median follow-up of 5.3 yrs, median OS is 6.4 yrs. 209 cases with recurrence or death were observed. The biologic risk model included relevant biomarkers, age and stage. See table for significant (p<.05) predictive markers after adjusting for age and stage. C-index is 0.66 for both models indicating adequate prediction accuracy. Conclusions: We have developed a biologic risk model predictive for recurrence in our large retrospective database. This is the first report of a risk model incorporating biomarkers and will be validated in our ongoing prospective study. DoD W81XWH-04-1-0142, NCIP01 91844. Hazard ratio RFS Hazard ratio OS Pathway Negative cytoplasmic(c-) pAMPK 1.54 1.49 Metabolism Positive membrane (m-) insulin receptor 1.44 n/a Proliferation Negative c-EpCAM 1.41 1.54 Differentiation Negative c- pmTOR 1.44 1.51 Metabolism High c-CXCR2 1.36 1.57 Inflammation High c- IGF1R (continuous variable) 1.004 n/a Proliferation Low m-CASK (continuous variable) 1.004 n/a Extracellular matrix interaction High nuclear FEN1 n/a 1.42 DNA repair

1376 ONCOLOGIC OUTCOMES OF PARTIAL (PN) VERSUS RADICAL NEPHRECTOMY (RN) FOR UNILATERAL WILMS TUMOR (UWT)

You have accessJournal of UrologyPediatrics: Stone Disease & Tumors1 Apr 20111376 ONCOLOGIC OUTCOMES OF PARTIAL (PN) VERSUS RADICAL NEPHRECTOMY (RN) FOR UNILATERAL WILMS TUMOR (UWT) Nicholas Cost, Jessica Lubahn, Heidi Penn, Candace Granberg, Bruce Schlomer, Jonathan Wickiser, Dinesh Rakheja, Patricio Gargollo, David Leonard, Linda Baker, and Vitaly Margulis Nicholas CostNicholas Cost Dallas, TX More articles by this author , Jessica LubahnJessica Lubahn Dallas, TX More articles by this author , Heidi PennHeidi Penn Kansas City, KS More articles by this author , Candace GranbergCandace Granberg Dallas, TX More articles by this author , Bruce SchlomerBruce Schlomer Dallas, TX More articles by this author , Jonathan WickiserJonathan Wickiser Dallas, TX More articles by this author , Dinesh RakhejaDinesh Rakheja Dallas, TX More articles by this author , Patricio GargolloPatricio Gargollo Dallas, TX More articles by this author , David LeonardDavid Leonard Dallas, TX More articles by this author , Linda BakerLinda Baker Dallas, TX More articles by this author , and Vitaly MargulisVitaly Margulis Dallas, TX More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1221AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES According to the Children's Oncology Group (COG) and International Society of Paediatric Oncology (SIOP), the recommended surgical management for UWT is RN. However, recent data demonstrate that when oncologically feasible, PN decreases the likelihood of chronic renal disease and associated co-morbidities. Thus, we analyzed oncologic outcomes of patients undergoing PN vs. RN for UWT. METHODS We searched Pub Med with the terms: “WT,” “Nephroblastoma,” “PN” and “Nephron Sparing Surgery.” Reviewing citations and eliminating repeat reports we found 19 groups presenting 115 patients treated with PN for UWT. These were analyzed for: stage, recurrence, recurrence location, and overall survival (OS). 82 patients from 16 groups had adequate data for analysis. As a comparison, the same endpoints were collected on all children who had RN for UWT from 1985-2010 at Children's Medical Center. RESULTS Of the 82 PN patients, 64 were stage I, 10 stage II, 6 stage III and 2 stage IV; however, this was a mix of patients staged/treated according to SIOP or COG protocols. Of the 121 RN patients, 24 were stage I, 45 stage II, 29 stage III and 23 stage IV. All of these children were treated in compliance with COG protocols. In the PN group, there were 9 total recurrences, 6 local recurrences, and 4 deaths. At a median follow up of 48mo (3–372) for the PN group, the recurrence free survival (RFS), local RFS and OS were 89.1%, 92.7% and 95.1% respectively. In the RN group, there were 20 total recurrences, 6 local recurrences, and 6 deaths. At a median follow up of 69.3mo (0.1–214.1) for the RN group, the RFS, local RFS and OS were of 83.1%, 95.0% and 95.0% respectively. When controlling for stage in a Cox Regression Analysis, there were no statistically significant differences in the above oncologic outcomes between the groups. The Hazard Ratio (HR) for the RN group vs. PN group was: for RFS HR=0.95 (95% CI 0.39–2.34), for local RFS HR=0.77 (95% CI 0.21–2.9) and for OS HR=0.45 (95% CI 0.17–4.39). CONCLUSIONS Based on reported data, the oncologic outcomes of PN for UWT in a select patient population do not appear to differ from those of RN. With the potential for renal preservation and its associated benefits, PN for appropriately selected patients should be studied in a prospective, cooperative group trial versus RN to definitively assess its role in management of UWT. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e549 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nicholas Cost Dallas, TX More articles by this author Jessica Lubahn Dallas, TX More articles by this author Heidi Penn Kansas City, KS More articles by this author Candace Granberg Dallas, TX More articles by this author Bruce Schlomer Dallas, TX More articles by this author Jonathan Wickiser Dallas, TX More articles by this author Dinesh Rakheja Dallas, TX More articles by this author Patricio Gargollo Dallas, TX More articles by this author David Leonard Dallas, TX More articles by this author Linda Baker Dallas, TX More articles by this author Vitaly Margulis Dallas, TX More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Impact of body mass index on clinical outcomes in triple‐negative breast cancer

Obesity is associated with poorer outcomes in patients with hormone receptor-positive breast cancers. This association is not well established for women with triple-negative breast cancers (TNBC). In this study, the prognostic effects of body mass index on clinical outcome were evaluated in patients with TNBC. A retrospective study was conducted on 418 patients who were treated between July 1996 and July 2010 for TNBC. Recurrence-free survival (RFS) and overall survival (OS) were evaluated in relation to body mass index (BMI) after controlling for clinically significant variables. One hundred twenty-four patients (29.7%) were normal/underweight (BMI ≤24.9 kg/m(2) ), 130 patients (31.1%) were overweight (BMI from 25 to 29.9 kg/m(2) ), and 164 patients (39.2%) were obese (BMI ≥30 kg/m(2) ). At a median follow-up of 37.2 months, there were 105 recurrences (25.1%) and 87 deaths (20.8%). Compared with normal/underweight patients, the multivariate hazard ratio (HR) for RFS was 0.81 (95% confidence interval [CI], 0.49-1.34) for obese patients. Similarly, OS was not associated with BMI category; obese patients had an HR of death of 0.94 (95% CI, 0.54-1.64) compared with normal/underweight patients. A Cox regression analysis identified the receipt of chemotherapy (HR, 0.25; 95% CI, 0.12-0.52), ductal histology (HR, 0.49; 95% CI, 0.25-0.97), stage III disease (HR, 3.5; 95% CI, 1.35-9.06), and increasing tumor size (HR, 1.19; 95% CI, 1.09-1.3) as independent prognostic factors for OS. No significant relation between obesity and RFS or OS emerged in patients with TNBC after controlling for clinically significant factors.

Effects of Perioperative Red Blood Cell Transfusion on Disease Recurrence and Survival After Pancreaticoduodenectomy for Ductal Adenocarcinoma

The premise that allogeneic red blood cell transfusion (RBCT) contributes to adverse oncologic outcomes after surgery remains controversial. We examined the effects of RBCT during and after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) on disease recurrence and survival. A prospective database of 220 patients undergoing PD for PDAC from 2000 to 2008 was reviewed and transfusion data collected. Univariate and multivariate analyses were performed for factors influencing RBCT, recurrence-free survival (RFS), and overall survival (OS). The effect of amount and timing (intraoperative vs. postoperative) of RBCT was analyzed. One hundred forty-seven patients (67%) received RBCT: 70 (32%) received 1 to 2 units, and 77 (35%) received >2 units. Median RFS and OS for the entire cohort was 12 and 16 months, respectively. RBCT of >2 units was associated with reduced RFS (9 vs. 15 months; P = 0.033) and OS (14 vs. 20 months; P = 0.003). Stratified by timing of transfusion, postoperative RBCT was associated with shortened RFS and OS. Controlling for age, body mass index, comorbidities, tumor factors, and major complications, each incremental unit of postoperative RBCT was associated with reduced RFS (hazard ratio 1.10, 95% confidence interval 1.02-1.18) and OS (hazard ratio 1.08, 95% confidence interval 1.03-1.12). Low hemoglobin and presence of comorbidities were the only preoperative factors independently associated with RBCT. Allogeneic red blood cell transfusion after PD for PDAC is independently associated with earlier cancer recurrence and reduced survival, in particular when administered postoperatively and in larger quantities. Blood-conservation methods are especially indicated for patients with preoperative anemia and medical comorbidities.

Evaluation of hormone receptor and benefit from adjuvant chemotherapy in breast cancer patients with intermediate- and high-risk disease.

6130 Background: The BRENDA Study network aims to improve quality of care for breast cancer patients by analyses of treatment related outcome within a network of specialized breast cancer centers in Germany. The population studied differs markedly from those populations found to be included in prospective trials. Despite a multitude of positive chemotherapy trials the role of adjuvant chemotherapy in subpopulations of breast cancer patients is still controversial. We investigated to which extent subpopulations of breast cancer patients defined by quantitative strong expression of hormone receptors benefit from adjuvant chemotherapy. Methods: Estrogen receptor (ER) and progesterone receptor (PR) content of 3,971 patients who received primary therapy for early breast cancer was recorded and quantified by standardized immunohistochemical evaluation. The Nottingham prognostic index (NPI) served to classify the patients' prognostic baseline risk. Results: Strong expression of ER and PR was found in 45% and 30.6%, respectively. In patients with strong expression of ER and/or PgR no significant difference with respect to recurrence free survival (RFS) and overall survival (OS) was found in patients receiving endocrine therapy alone or in combination with chemotherapy. Calculated hazard ratios for RFS were 0.98 for patients with intermediate risk (95% CI: 0.48-2.01; p = 0.949) and 1.03 for high-risk patients (CI: 0.46-2.31; p = 0.948). Risk of recurrence was significantly increased in patients receiving chemotherapy only when compared with patients receiving additional or alternative hormonal therapy in the high-risk group of patients (HR = 2.45; CI: 1.04-5.80; p = 0.042). Conclusions: The incremental benefit of chemotherapy when added to a hormonal therapy regimen in patients with quantitative strong hormone receptor expression has to be questioned. Algorithms based on patients risk alone might cause overtreatment with ineffective chemotherapy in a considerable fraction of patients receiving treatment outside clinical trials. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Novartis, Pfizer

Outcomes after breast cancer in an ethnically diverse cohort of high-risk patients: Differences in survival based on BRCA1/BRCA2 mutation status

21116 Background: Most studies of hereditary breast cancer report that BRCA1 associated tumors are characterized by high grade and hormone receptor negativity, while those associated with BRCA2 are more similar to sporadic cases. Several groups have demonstrated that BRCA1 mutations, but not BRCA2 mutations, are associated with reduced survival in women with breast cancer. These studies have primarily included women of European and Ashkenazi Jewish heritage. No study to date has assessed outcomes in an ethnically diverse cohort of high-risk individuals. Methods: High-risk individuals were identified through the University of Chicago Cancer Risk Clinic (UCCRC). Clinicopathologic data was collected on all patients with breast cancer who had undergone genetic testing and consented to inclusion in research protocols. Recurrence-free survival (RFS) and overall survival (OS) for BRCA1, BRCA2 and non-carriers was compared using the log-rank test. Hazard ratios (HR) and 95% Confidence Intervals (95% CI) were calculated from Cox proportional hazard models. Results: 280 patients from 258 families were studied. 67 were BRCA1 mutation positive, 36 were BRCA2 positive and 177 were non-carriers. 65% of patients were non-Hispanic non-Jewish whites, 15% African American, 15% Ashkanazi Jewish, 3% Hispanic and 2% Asian. At a median follow up of 5 years, 40 patients had relapsed and 22 had died. HRs (95% CI) for RFS of the BRCA1 and BRCA2 carriers relative to non-carriers were 1.6 (0.77–3.33) and 1.3 (0.55–3.09) respectively, when adjusted for year at diagnosis. The adjusted HRs (95% CI) for OS for the BRCA1 and BRCA2 carriers relative to non-carriers were 1.82 (0.48–3.02) and 0.67 (0.15–3.04), respectively. Conclusions: In this study of an ethnically diverse cohort of high-risk individuals, BRCA1 mutation carriers had a poorer outcome as compared to those with BRCA2 mutations or those without identifiable mutations in either gene, although this difference was not statistically significant. This observation is consistent with previous studies of women of predominantly Ashkenzi Jewish and European ancestry. This study was funded by the Falk Medical Research Trust, the Breast Cancer Research Foundation and the Entertainment Industry Fund. No significant financial relationships to disclose.