Citations

420 Background: Cytoreductive nephrectomy (CN) has been associated with significant morbidity, but there is little data identifying patients at increased risk. We evaluated the association of clinicopathologic features with early post-operative complications and prolonged length of stay (pLOS) among CN patients. Methods: We identified 294 patients treated with radical nephrectomy for M1 renal cell carcinoma between 1990 and 2009 at the Mayo Clinic. All complications within 30 days of surgery were reported using standardized methodology according to the Clavien classification. Associations with the presence of any early complication and pLOS (defined as ≥8 days, the top 25th percentile) were evaluated using logistic regression models. Results: Thirty-five (12%) patients experienced at least one early complication and 15 (5%) patients experienced at least one Clavien grade ≥3 early complication. The median LOS was 6 days (IQR 5-7), and 68 (23%) patients had a pLOS. On univariate analysis, liver metastases, symptomatic presentation, intraoperative transfusion, and pathologic nodal stage were significantly associated with both early complications and pLOS (Table). Two multivariate models were constructed. In Model 1 (limited to pre-operative features), only liver metastases (p<0.01) were associated with early complications while liver metastases (p=0.01) and open approach (p=0.02) were associated with pLOS. In Model 2 (all variables included), liver metastases (p=0.01), intraoperative transfusion (p<0.01), and high nuclear grade (p<0.01) were associated with early complications while intraoperative transfusion (p<0.01) and positive nodes (p=0.05) were associated with pLOS. Conclusions: CN was associated with a low incidence of early post-operative complications, particularly Clavien ≥3 complications. Presence of liver metastases and intraoperative transfusion were independently associated with increased risk of both complications and pLOS. [Table: see text]

4 Background: Management of patients with a postoperative rising prostate-specific antigen (PSA) level is complex. Additional local treatment such as salvage radiation therapy (SRT) may be sufficient for many patients but some may require concurrent systemic therapy in order to delay or prevent metastatic disease. As PSA recurrence on its own is a poor surrogate for metastatic disease we hypothesized that the Decipher genomic classifier (GC), a validated predictor of metastasis may be able to better distinguish those patients where additional therapy is beneficial from those where SRT on its own is likely sufficient. Methods: Genomic classifier (GC) scores were calculated from 170 prostate cancer patients, who received SRT at the Veteran Affairs Medical Center Durham, Thomas Jefferson University and Mayo Clinic, between 1990 and 2010. SRT was defined as administration of RT with Pre-RT PSA levels > 0.2 ng/ml. GC and CAPRA-S scores were compared using survival c-index, competing-risks and Cox regression analysis for the prediction of metastasis. Results: Survival c-index for predicting metastasis 5 years post SRT was 0.85 (95% CI: 0.73-0.88) for GC and 0.63 (95% CI: 0.49-0.77) for CAPRA-S. The cumulative incidence of metastasis at 5 years post-SRT was 2.7%, 8.4%, and 33.1% for low, average, and high GC scores (p < 0.001) and 16.9%, 2.3% and 17.2% for low, average and high CAPRA-S scores (p = 0.113). In univariable analysis only GC, extraprostatic extension, path GS and Pre-RT PSA were significant predictors of metastasis. In multivariable analyses with clinical risk factors or the CAPRA-S risk model, GC was the only independent predictor of metastasis with a HR of 1.63 (1.22-2.18, p < 0.001) for a 10% unit increase in risk score. Conclusions: In patients treated with postoperative SRT for PSA recurrence, GC is a powerful predictor of metastasis. Patients with low Decipher have excellent prognosis with SRT and may avoid concurrent hormonal therapy. Patients with high Decipher risk are at highest risk for metastatic disease and SRT failure and may benefit from intensified systemic therapy.

PURPOSE: Yttrium-90 ibritumomab tiuxetan (IDEC-Y2B8) is a murine immunoglobulin G1 kappa monoclonal antibody that covalently binds MX-DTPA (tiuxetan), which chelates the radioisotope yttrium-90. The antibody targets CD20, a B-lymphocyte antigen. A multicenter phase I/II trial was conducted to compare two doses of unlabeled rituximab given before radiolabeled antibody, to determine the maximum-tolerated single dose of IDEC-Y2B8 that could be administered without stem-cell support, and to evaluate safety and efficacy.PATIENTS AND METHODS: Eligible patients had relapsed or refractory (two prior regimens or anthracycline if low-grade disease) CD20+B-cell low-grade, intermediate-grade, or mantle-cell non-Hodgkin's lymphoma (NHL). There was no limit on bulky disease, and 59% had at least one mass ≥ 5 cm.RESULTS: The maximum-tolerated dose was 0.4 mCi/kg IDEC-Y2B8 (0.3 mCi/kg for patients with baseline platelet counts 100 to 149,000/μL). The overall response rate for the intent-to-treat population (n = 51) was 67% (26% complete response [CR]; 41% partial response [PR]); for low-grade disease (n = 34), 82% (26% CR; 56% PR); for intermediate-grade disease (n = 14), 43%; and for mantle-cell disease (n = 3), 0%. Responses occurred in patients with bulky disease (≥ 7 cm; 41%) and splenomegaly (50%). Kaplan-Meier estimate of time to disease progression in responders and duration of response is 12.9+ months and 11.7+ months, respectively. Adverse events were primarily hematologic and correlated with baseline extent of marrow involvement with NHL and baseline platelet count. One patient (2%) developed an anti-antibody response (human antichimeric antibody/human antimouse antibody).CONCLUSION: These phase I/II data demonstrate that IDEC-Y2B8 radioimmunotherapy is a safe and effective alternative for outpatient therapy of patients with relapsed or refractory NHL. A phase III study is ongoing.

We described physical activity measures and hourly patterns in patients with chronic obstructive pulmonary disease (COPD) after stratification for generic and COPD-specific characteristics and, based on multiple physical activity measures, we identified clusters of patients. In total, 1001 patients with COPD (65% men; age, 67 years; forced expiratory volume in the first second [FEV 1 ], 49% predicted) were studied cross-sectionally. Demographics, anthropometrics, lung function and clinical data were assessed. Daily physical activity measures and hourly patterns were analysed based on data from a multisensor armband. Principal component analysis (PCA) and cluster analysis were applied to physical activity measures to identify clusters. Age, body mass index (BMI), dyspnoea grade and ADO index (including age, dyspnoea and airflow obstruction) were associated with physical activity measures and hourly patterns. Five clusters were identified based on three PCA components, which accounted for 60% of variance of the data. Importantly, couch potatoes (i.e. the most inactive cluster) were characterised by higher BMI, lower FEV 1 , worse dyspnoea and higher ADO index compared to other clusters ( p < 0.05 for all). Daily physical activity measures and hourly patterns are heterogeneous in COPD. Clusters of patients were identified solely based on physical activity data. These findings may be useful to develop interventions aiming to promote physical activity in COPD.

348 Background: While the initial natural history after surgical resection for localized renal cell carcinoma (RCC) has been well-characterized, recurrence patterns for patients who experience late recurrence of disease continue to be defined. Here, we evaluated the clinical characteristics and survival of patients who experienced disease recurrence > 5 years following nephrectomy. Methods: We identified 1,454 patients who were treated with radical nephrectomy (RN) or nephron-sparing surgery (NSS) for unilateral, sporadic pT1-4NxM0 RCC between 1970-2000 and who had remained free of disease for 5 years after surgery. Late (> 5 years) recurrence was then recorded and was classified as renal (ipsilateral/contralateral kidney) recurrence and distant (all other sites) recurrence. The incidence of late recurrence was estimated using the Kaplan Meier method, and clinicopathological variables subsequent disease relapse were analyzed using Cox proportional hazard regression models. Results: Median follow-up after nephrectomy in the cohort here was 13.9 years (range 5.1-38.9). In total, 63 patients experience a late recurrence in the ipsilateral/contralateral kidney, at a median of 9.3 years (range 5.1-25.3) after surgery. 172 (11.8%) patients developed late distant metastases, at a median of 9.6 years (range: 5.1-26.6). Estimated recurrence-free survival at 10 and 15 years following nephrectomy was 97.3% and 95.2% for renal recurrence and 93.1% and 85.9% for distant recurrence, respectively. Increased tumor size (HR 1.1; p<0.001) was associated with a higher rate of late renal recurrence, while increased tumor size (HR 1.1; p=0.018), clear cell or collecting duct histology (HR 3.7; p<0.001), and tumor stage pT1b (HR 2.8; p<0.001), pT2a (HR 4.5; p<0.001), pT2b (HR 3.4; p=0.007), and pT3/4 (HR 5.1; p<0.001) were predictive of the development of late distant metastasis. Conclusions: Patients undergoing surgery for localized RCC remain at life-long risk of disease recurrence. Approximately 5% experience renal recurrence and 15% demonstrate distant relapse, during the ensuing 10 years. Continued investigation to identify potential site-specific predictors of late recurrence is necessary to guide postoperative surveillance regimens. No significant financial relationships to disclose.

175 Background: The efficient delivery of adjuvant and salvage therapy after radical prostatectomy in patients with prostate cancer is hampered by a lack of biomarkers to assess the risk of clinically significant recurrence and progression. Methods: Mayo Clinic Radical Prostatectomy Registry (RP) patient specimens were selected from a case-control cohort with 14 years median follow-up for training and initial validation of an expression biomarker genomic classifier (GC). An independent, blinded case-cohort study of high-risk RP subjects was used to validate GC, comparing the performance of GC to a multivariate logistic regression clinical model (CM) and GC combined with clinical variables (genomic-clinical classifier, GCC) for predicting clinical recurrence (defined as positive bone or CT scan within 5 years after biochemical recurrence). The concordance index (c-index) and Cox model were used to evaluate discrimination and estimate the risk of clinical recurrence. Results: In the training subset (n=359), both GC and GCC had a c-index of 0.90 whereas CM had a c-index of 0.76. In the internal validation set (n=186), GC and GCC had a c-index of 0.76 and 0.75, while CM had a c-index of 0.69. In an independent high-risk study (n=219), GC and GCC had a c-index of 0.77 and 0.76, while CM had a c-index of 0.68. In subset analysis of Gleason score 7 patients within the high-risk group, GC and GCC showed improved discrimination with c-index of 0.78 and 0.76, respectively compared to 0.70 for CM. In the high-risk group, the risk of recurrence by GC model score quartiles at 5 years after RP was estimated at 1%, 5%, 5% and 18%. Conclusions: The GC model shows improved performance over CM in the prediction of clinical recurrence in a high-risk cohort and in subset analysis of Gleason score 7 patients. The addition of clinical variables to the GC model did not significantly contribute to classifier performance in patients with high-risk features. We are further testing the performance of the GC and GCC models and their usefulness in guiding decision-making (e.g., for the adjuvant therapy setting) in additional studies of prostate cancer clinical risk groups.

AbstractPurposeStem cell transplant (SCT) recipients commonly undergo bronchoalveolar lavage (BAL) collection as an infectious pulmonary work‐up. Previous studies report the utility and overall diagnostic yield of fiberoptic bronchoscopy with BAL in this vulnerable population, though none focused purely on microbiologic yield or made comparisons with less invasive means of pathogen detection. We sought to determine and elaborate on the microbiologic yield of BAL in SCT recipients, assess a correlation between BAL studies and less invasive means of pathogen detection, and assess the utility of repeating a BAL within 30 days.MethodsBetween January 1, 2009, and July 31, 2013, we reviewed medical records of 125 SCT recipients who underwent 179 BALs. In addition to demographic information and details pertaining to their SCT, a comprehensive review of their microbiologic data was performed and recorded.ResultsOur study showed an overall BAL microbiologic yield of 40%, despite 92% of patients receiving broad‐spectrum antimicrobial therapy at the time of the BAL procedure.ConclusionsAlthough an initial BAL sample in this population provides crucial microbiologic information, repeating the procedure within 30 days may have minimal additional microbiologic yield. BAL continues to be an essential diagnostic tool in SCT recipients undergoing an infectious pulmonary work‐up.