Multivariable Competing-risks Regression Analyses Research Articles

Metroticket 2.0 Model for Analysis of Competing Risks of Death After Liver Transplantation for Hepatocellular Carcinoma

Outcomes of liver transplantation for hepatocellular carcinoma (HCC) are determined by cancer-related and non-related events. Treatments for hepatitis C virus infection have reduced non-cancer events among patients receiving liver transplants, so reducing HCC-related death might be an actionable end point. We performed a competing-risk analysis to evaluate factors associated with survival of patients with HCC and developed a prognostic model based on features of HCC patients before liver transplantation. We performed multivariable competing-risk regression analysis to identify factors associated with HCC-specific death of patients who underwent liver transplantation. The training set comprised 1018 patients who underwent liver transplantation for HCC from January 2000 through December 2013 at 3 tertiary centers in Italy. The validation set comprised 341 consecutive patients who underwent liver transplantation for HCC during the same period at the Liver Cancer Institute in Shanghai, China. We collected pretransplantation data on etiology of liver disease, number and size of tumors, patient level of α-fetoprotein (AFP), model for end-stage liver disease score, tumor stage, numbers and types of treatment, response to treatments, tumor grade, microvascular invasion, dates, and causes of death. Death was defined as HCC-specific when related to HCC recurrence after transplantation, disseminated extra- and/or intrahepatic tumor relapse and worsened liver function in presence of tumor spread. The cumulative incidence of death was segregated for hepatitis C virus status. In the competing-risk regression, the sum of tumor number and size and of log10 level of AFP were significantly associated with HCC-specific death (P < .001), returning an average c-statistic of 0.780 (95% confidence interval, 0.763-0.798). Five-year cumulative incidence of non-HCC-related death was 8.6% in HCV-negative patients and 18.1% in HCV-positive patients. For patients with HCC to have a 70% chance of HCC-specific survival 5 years after transplantation, their level of AFP should be <200 ng/mL and the sum of number and size of tumors (in centimeters) should not exceed 7; if the level of AFP was 200-400 ng/mL, the sum of the number and size of tumors should be ≤5; if their level of AFP was 400-1000 ng/mL, the sum of the number and size of tumors should be ≤4. In the validation set, the model identified patients who survived 5 years after liver transplantation with 0.721 accuracy (95% confidence interval, 0.648%-0.793%). Our model, based on patients' level of AFP and HCC number and size, outperformed the Milan; University of California, San Francisco; Shanghai-Fudan; Up-to-7 criteria (P < .001); and AFP French model (P= .044) to predict which patients will survive for 5 years after liver transplantation. We developed a model based on level of AFP, tumor size, and tumor number, to determine risk of death from HCC-related factors after liver transplantation. This model might be used to select end points and refine selection criteria for liver transplantation for patients with HCC. To predict 5-year survival and risk of HCC-related death using an online calculator, please see www.hcc-olt-metroticket.org/. ClinicalTrials.gov IDNCT02898415.

Employment after heart transplantation among adults with congenital heart disease.

Adults with congenital heart disease may require heart transplantation for end-stage heart failure. Whereas heart transplantation potentially allows adults with congenital heart disease to resume their usual activities, employment outcomes in this population are unknown. Therefore, we investigated the prevalence and predictors of work participation after heart transplantation for congenital heart disease. Retrospective review of a prospective registry. United Network for Organ Sharing registry of transplant recipients in the United States. Adult recipients of first-time heart transplantation with a primary diagnosis of congenital heart disease, performed between 2004 and 2015. None. Employment status reported by transplant centers at required follow-up intervals up to 5y posttransplant. Among 470 patients included in the analysis (mean follow-up: 5±3y), 127 (27%) worked after transplant, 69 (15%) died before beginning or returning to work, and 274 (58%) survived until censoring, but did not participate in paid work. Multivariable competing-risks regression analysis examined characteristics associated with posttransplant employment, accounting for mortality as a competing outcome. In descriptive and multivariable analysis, pretransplant work participation was associated with a greater likelihood of posttransplant employment, while the use of Medicaid insurance at the time of transplant was associated with a significantly lower likelihood of working after transplant (subhazard ratio compared to private insurance: 0.55; 95% confidence interval: 0.32, 0.95; P=.032). Employment was rare after heart transplantation for congenital heart disease, and was significantly less common than in the broader population of adults with congenital heart disease. Differences in return to work were primarily related to pretransplant employment and the use of public insurance, rather than clinical characteristics.

PD72-05 NATURAL HISTORY OF PATIENTS TREATED WITH SALVAGE RADIATION THERAPY FOR RISING PSA AFTER RADICAL PROSTATECTOMY: A LONG-TERM SURVIVAL ANALYSIS

PD72-05 NATURAL HISTORY OF PATIENTS TREATED WITH SALVAGE RADIATION THERAPY FOR RISING PSA AFTER RADICAL PROSTATECTOMY: A LONG-TERM SURVIVAL ANALYSIS

Impact of treatment on progression to castration-resistance, metastases, and death in men with localized high-grade prostate cancer.

Men with high‐grade prostate cancer (HGPC) are at greatest risk of disease progression. Clinical risk factors associated with castration‐resistant prostate cancer (CRPC), metastases, and prostate cancer‐specific mortality (PCSM) were identified in a contemporary HGPC cohort. Clinical data was collected from men diagnosed with Gleason sum (GS) ≥8 at the Greater Los Angeles Veterans Affairs (GLA‐VA) Healthcare System between 2000 and 2013. Multivariable competing risks regression analyses assessed progression to CRPC, metastases, and PCSM within three treatment strata. The cumulative incidence of disease progression was calculated at 2, 5, and 10‐year time points. Review of 2149 prostate cancer cases yielded 322 with HGPC. Median survival times for cancer‐specific and overall mortality were significantly shorter in men treated with primary androgen deprivation therapy (ADT) (P = 0.0002 and P < 0.0001). Multivariable analyses revealed that clinical stage N1, GS 10, and treatment with primary ADT were significantly associated with increased risk of CRPC, metastases, and PCSM. Significant differences in these outcomes were not observed in men treated with radical prostatectomy (RP) when compared to those treated with radiation therapy combined with short‐term ADT (XRT‐ADT). Ten‐year event rates of progression to CRPC, metastases, and PCSM, for men treated with primary ADT, were 45.5%, 25.4%, and 25.1%, respectively. In conclusion, GS 10 and lymph node involvement, as well as primary ADT treatment in men with HGPC was associated with increased risk of CRPC, metastases, and PCSM. Curative‐intent treatment with RP or XRT‐ADT is associated with reduced progression rates and death in men with HGPC.

OR40 High cell free DNA (CFDNA) recipient chimerism during early post-transplant period predicts clinically significant graft versus host disease

Aims Development of Graft versus host disease (GVHD), one of the most common and debiliating complications of allogeneic Hematopoeitic cell Transplantation (HCT) is conceptualized in the following four sequential events: killing of recipient cells by induction chemo- and radio-therapy leading to exposure of recipient antigens, activation of the antigen presenting cells, donor T cell stimulation, and target tissue destruction. As a result, the dying host tissue cells (either due to induction therapy or allo-immune responses) release small cell-free DNA molecules (cf-DNA) into the circulation. In this study, we analyzed whether recipient chimerism in circulating cf-DNA during early post-transplant period can either influence or predict ensuing GVHD. Methods cfDNA was extracted from a total of 88 serum specimens from 44 HCT recipients at one week and one month after transplant. PCR amplification of a panel of 15 fluorochrome-labelled STR markers followed by their size fractionation through capillary electrophoresis was performed to quantify recipient chimerism in cfDNA. The ’cut off’ for cfDNA recipient chimerism was determined by receiver operating characteristic (ROC) curve and its correlation with clinically significant GVHD (grade II-IV acute GVHD and/or chronic GVHD requiring systemic therapy) was analyzed using multivariate competing risk regression analysis. Results High cfDNA recipient chimerism one week after HCT was found to be associated with clinically significant GVHD (p = 0.03, Fig. 1a). Recipient cfDNA chimerism cutoff of 73% calculated by ROC analysis strongly correlated with the cumulative incidence of clinically significant GVHD (p = 0.003, HR = 7; 95% CI = 2–25.3, Fig. 1b). Recipient cfDNA chimerism one month after HCT was not associated with GVHD. Download high-res image (133KB) Download full-size image Conclusions Strong correlation of high cfDNA recipient chimerism one week after HCT with GVHD suggests that killing of host cells by induction therapy may play an important role in triggering allo-immune responses culminating into GVHD.

MP09-16 CONTEMPORARY MAPPING OF POST-PROSTATECTOMY PROSTATE CANCER RELAPSE WITH C-11 CHOLINE PET AND MULTIPARAMETRIC MRI

INTRODUCTION AND OBJECTIVES: The aim of this study was to develop and externally validate a novel model aimed at predicting cancer-specific mortality (CSM) after biochemical recurrence (BCR) among prostate cancer (PCa) patients treated with radical prostatectomy (RP) with or without adjuvant external beam radiotherapy (aRT) and/or hormonal therapy (aHT). METHODS: The development cohort included 689 consecutive PCa patients treated with RP between 1987 and 2011 at a single tertiary referral center. All men had a subsequent BCR, defined as 2 subsequent PSA values>0.2 ng/ml and rising. Multivariable competingrisks regression analyses tested the predictors of CSM after BCR for purpose of 5-year CSM nomogram development. Validation (2,000 bootstrap resamples) was internally tested. External validation was performed into a population of 6,734 PCa patients with BCR after treatment with RP treated at another tertiary referral center from 1987 to 2011. The predictive accuracy (PA) was quantified using the receiver operating characteristic-derived area under the curve and the calibration plot method. RESULTS: The 5-year CSM-free survival rate was 83.6% (CI: 79.6-87.2). At multivariable analyses, pathologic stage T3b or more (HR: 7.42; p1⁄40.008), pathologic Gleason score 8-10 (HR: 2.19; p1⁄40.003), lymph node invasion (HR: 3.57; p1⁄40.001), time to BCR (HR: 0.99; p1⁄40.03) and age at BCR (HR: 1.04; p1⁄40.04), were each significantly associated with the risk of CSM after BCR. The bootstrap-corrected PA was 87.4% (bootstrap 95% CI: 82.0-91.7%). External validation of our nomogram showed a good PA of 83.2%. Figure 1 shows the competing-risk nomogram CONCLUSIONS: We developed and externally validated the first nomogram for individual prediction of 5-year PCa-specific mortality after BCR, applicable to all contemporary patients who recur after RP, inclusive of those treated with adjuvant therapies. This accurate and generalizable tool could be useful for patient counseling, risk stratification, and in designing future randomized trials to determine the decision making process in the BCR patient population

Predictors of outcomes in children awaiting heart transplantation: an experience from a National Paediatric Heart Transplantation Programme.

The risk of mortality while awaiting heart transplantation (HT) may be greater in the setting of a smaller population and lower donor organ rates. Optimizing allocation policy and identifying the most vulnerable patients will help reduce mortality. As such, we aimed to evaluate the predictors of outcomes in patients awaiting HT as part of a National Paediatric HT Programme. Between 1988 and 2015, 200 children were listed for HT as part of a National Paediatric HT Programme. We categorized patients as experiencing one of four competing events: (i) transplant, (ii) death, (iii) delisting for clinical deterioration and (iv) delisting for clinical improvement. Comparison was made across three study eras: Era 1: 1988-95; Era 2: 1996-2005; Era 3: 2006-15. A multivariable competing risk regression analysis was performed to determine the independent predictors of transplantation and the composite event of death or delisting for clinical deterioration. Among the 200 patients listed, 60% (119/200) underwent transplantation, 22% (44/200) died on the waiting list, 7% (13/200) were delisted for clinical deterioration and 11% (21/200) were delisted due to clinical improvement, with 2% (3/200) being still active on the waiting list. The mortality-rate for patients who remained on the waiting list decreased from 27% in Era 1 to 18% in Era 3. The survival from wait-listing was 57, 47 and 39% at 5, 10 and 15 years, respectively. On multivariable competing risk regression, older age (HR 1.09, 95% CI 1.01-1.18, P = 0.029) and the absence of inotropic support (HR 2.22, 1.23-4.00, P = 0.0073) were predictors of reaching transplantation. Higher creatinine (per 20 µmol/l, HR 1.42, 1.03-1.95, P = 0.03) was a predictor of the composite endpoint of death or delisting for deterioration. In this analysis of a National Paediatric HT Programme, waiting-list mortality has decreased over time though it remains higher than countries with higher donor rates. The requirement for inotropic support and worsening renal function were predictors of failure to reach transplantation. These patients are likely to benefit the most from ventricular-assist device therapy and higher priority listing.

Predictors of clinical outcomes in patients with neuropsychiatric systemic lupus erythematosus

IntroductionNeuropsychiatric systemic lupus erythematosus (NPSLE), a serious organ disorder with a variety of symptoms, has diverse therapeutic outcomes because of the variability of NPSLE manifestations. A comprehensive association study of NPSLE among clinical and immunopathogenic aspects and outcomes has not been conducted. MethodsWe analyzed the laboratory data, NPSLE symptoms, and clinical outcomes at 1yr post-treatment and the profiles of 27 cytokines, chemokines and growth factors in cerebrospinal fluid (CSF) samples using the Bio-Plex Human 27-plex panel from 28 NPSLE patients. Univariate and multivariable competing risks regression analyses were used to determine the predictive factors of clinical response. We also tried to predict the outcome of NPSLE by the 27 cytokines/chemokines/growth factors using a weighted-voting (WV) algorithm. ResultsOf the two males and 26 females (92.9%), 16 were non-responders at 1yr post-treatment; in the final model, the independent predictors of non-responders were longer disease durations of SLE (odds ratio [OR]: 1.490, 95% confidence interval [CI]: 1.143–2.461, p=0.0003) and patients with more than one NPSLE symptom types (OR: 15.14, 95% CI: 1.227–452.1, p=0.0334). The pretreatment CSF interleukin (IL)-6, IL-10, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) levels were significantly higher in the non-responders (p=0.0207, p=0.0054, p=0.0242 and p=0.0077, respectively). We identified six “minimum predictive markers:” IL-10, TNF-α, IL-6, IFN-γ, IL-4 and IL-13 by a WV algorithm that showed the highest accuracy (70.83%) and highest Matthews correlation coefficient (54.23%). ConclusionsWe have devised a numerical prediction scoring system that was able to separate the non-responders from responders. The patients with longer disease durations of SLE and those with more than one NPSLE symptom types had poorer outcomes. Our findings may indicate both the importance of making a diagnosis at an earlier phase for better therapeutic response and the usefulness of measuring multiple cytokines to predict NPSLE therapeutic outcomes.

Predicting survival of men with recurrent prostate cancer after radical prostatectomy

IntroductionTo develop and externally validate a novel nomogram aimed at predicting cancer-specific mortality (CSM) after biochemical recurrence (BCR) among prostate cancer (PCa) patients treated with radical prostatectomy (RP) with or without adjuvant external beam radiotherapy (aRT) and/or hormonal therapy (aHT). Materials & methodsThe development cohort included 689 consecutive PCa patients treated with RP between 1987 and 2011 with subsequent BCR, defined as two subsequent prostate-specific antigen values >0.2 ng/ml. Multivariable competing-risks regression analyses tested the predictors of CSM after BCR for the purpose of 5-year CSM nomogram development. Validation (2000 bootstrap resamples) was internally tested. External validation was performed into a population of 6734 PCa patients with BCR after treatment with RP at the Mayo Clinic from 1987 to 2011. The predictive accuracy (PA) was quantified using the receiver operating characteristic-derived area under the curve and the calibration plot method. ResultsThe 5-year CSM-free survival rate was 83.6% (confidence interval [CI]: 79.6–87.2). In multivariable analyses, pathologic stage T3b or more (hazard ratio [HR]: 7.42; p = 0.008), pathologic Gleason score 8–10 (HR: 2.19; p = 0.003), lymph node invasion (HR: 3.57; p = 0.001), time to BCR (HR: 0.99; p = 0.03) and age at BCR (HR: 1.04; p = 0.04), were each significantly associated with the risk of CSM after BCR. The bootstrap-corrected PA was 87.4% (bootstrap 95% CI: 82.0–91.7%). External validation of our nomogram showed a good PA at 83.2%. ConclusionsWe developed and externally validated the first nomogram predicting 5-year CSM applicable to contemporary patients with BCR after RP with or without adjuvant treatment.

Histologic Confirmation for Patients Presenting with Gastrointestinal Graft Versus Host Disease: How to Interpret Histologic Grade 1 (Does It Matter)?

Introduction: Gastrointestinal Graft Versus Host Disease (GI GVHD) is a leading cause for non-relapse mortality (NRM) following allogeneic hematopoietic cell transplantation. Histologic confirmation of GI GVHD via endoscopic biopsy is considered standard practice with histologic grading reported as grades 0-4. Histologic grade 3-4 (crypt drop out/ broad areas of denudation) has been found to correlate with clinical severity and very high NRM. However, the prognostic value for the more common histologic grade 1 (increased apoptotic bodies) has been poorly described, leading to confusion in rendering therapy in patients with this finding. The goal of this study was to determine the impact on NRM for patients with histologic grade 1 in context of the presenting clinical stage.Methods: We evaluated 309 consecutive patients who underwent an initial, histologic confirmation for suspected GI GVHD within the first 6 months post-transplant between the years of 2009- 2012 at MD Anderson. The majority of the patients underwent an upper GI endoscopy with random biopsies obtained from the antrum and body of the stomach and duodenum along with an un-prepped sigmoidoscopy with random rectal biopsies. All slides were re-reviewed by a single pathologist experienced in GI GVHD. The overall histologic grade for a patient was defined as the maximum grade identified in any biopsy site. The presence of 4 or more apoptotic bodies in a biopsy fragment was required for histologic grade 1, and a biopsy fragment with 3 or fewer apoptotic bodies (formerly suggestive of or cannot exclude GVHD) was classified as negative (histologic grade 0). In order to be considered as negative for GVHD, the absence of apoptotic bodies was required for all biopsy fragments. Clinical stage 0 refers to patients who underwent endoscopic biopsy for mild lower GI GVHD symptoms but not severe enough for clinical stage 1, and remainder clinical stages were defined based on standard criteria.Results: Patient characteristics are described in Table 1. A total of 82 (26%), 101 (32%), 28 (9%), 53 (17%), and 45 (15%) patients were classified as having GI GVHD histologic grade 0-4, respectively. The distribution of histologic grade according to presenting clinical stage is shown in Figure 1. In univariate analysis, the presence of histologic grade 1 did not influence NRM for patients with isolated upper GI GVHD (HR 0.8, p=0.6), but was associated with increased NRM (HR 2.4, p=0.02) in patients with lower GI GVHD. Among patients with lower GI GVHD, the 4-years cumulative incidence (CI) of NRM was significantly higher in patients with clinical stages 3-4 versus 0-2 (61% vs 41%, p 0.002). However, the proportion of histologic grade 1 was comparable between these two groups (23% vs 32%, p=0.2). Therefore, we assessed the impact of histologic grade 1 in lower GI GVHD stratifying for clinical stage (0-2 vs 3-4). In univariate analysis, histologic grade 1 did not lessen the severity of GVHD in patients with clinical stage 3-4 (4-years % CI: 83%). In contrast, histologic grade 1 was associated with increased NRM in clinical stage 0-2 compared with histologic grade 0 (4-years % CI: 48% vs 18%). Multivariate competing-risk regression analysis confirmed the independent impact of histologic grade 1 in patients with clinical stages 0-2 (HR=3.05, p= 0.025) (Figure 2). The presence of multiple versus single positive biopsy site for histologic grade 1 did not influence NRM.Conclusion: Histologic grade 1 GI GVHD is not synonymous with "mild" GVHD and clinicians should use the term "mild" only to reflect clinical stage. The presence of histologic grade 1 in patients presenting with lower GI GVHD clinical stage 0-2 should not be dismissed since it independently impacts outcomes with 3-fold increased NRM. For patients who present with advanced lower GI GVHD (clinical stage 3-4), the presence of histology grade 1 does not lessen the markedly adverse impact of advanced clinical stage GVHD. [Display omitted] [Display omitted] [Display omitted] DisclosuresAlousi:Therakos, Inc: Research Funding.

Does postoperative radiation therapy impact survival in non-metastatic sarcomatoid renal cell carcinoma? A SEER-based study.

The effect of adjuvant radiation therapy on survival in sarcomatoid renal cell carcinoma (sRCC) with no evidence of distant metastasis remains unclear. Subjects diagnosed with non-metastatic sRCC were identified using the Surveillance Epidemiology and End Results (SEER) (2004-2012) database and divided into groups based on their surgical treatment (ST): no surgery or radiation therapy (NSR); partial nephrectomy (PNE); radical nephrectomy with ureterectomy and bladder cuff resection (RNE + UE + BLAD); and radical nephrectomy (RNE). Certain radical nephrectomy cases also received adjuvant external-beam radiation therapy (RNE + RAD). The Kaplan-Meier method was used to estimate overall survival (OS). A multivariable competing risks regression analysis was used to calculate disease-specific survival (DSS) probability and to determine factors associated with cause-specific mortality (CSM). A total of 408 patients were included in this study. The 5-year OS and predicted DSS were significantly higher in the patients who underwent STs (i.e., PNE, RNE + UE + BLAD, RNE, and RNE + RAD) (20.1-54.0 and 20.1-59.9 %, respectively) than in the NSR group (9.0 and 11.6 %, respectively) (P < 0.001). ST was independently associated with a decreased CSM (P < 0.0001). No significant differences in OS or the 1-, 3-, or 5-year DSS probabilities between the RNE and RNE + RAD groups were observed. RNE + RAD was not significantly associated with a decrease in 1-year CSM [subhazard ratio (SHR) 0.95; 95 % CI 0.23-3.96; P = 0.947]. Adjuvant external-beam radiation therapy did not increase OS in non-metastatic sRCC patients.

Surveillance Following Nephron-Sparing Surgery: An Assessment of Recurrence Patterns and Surveillance Costs

To assess the pattern of renal cell carcinoma (RCC) recurrences in nephron-sparing surgery (NSS) patients, and to determine whether current guidelines for surveillance could be modified based on such patterns. Retrospective review of a single-institution NSS database. Pattern of RCC recurrences and factors associated with recurrence were analyzed using univariate and multivariable competing risk regression analyses. Cost of surveillance was estimated based on Medicare charges. A total of 505 patients underwent elective NSS for RCC. Pathologic T stage included 394 pT1a and 79 pT1b lesions. Median follow-up was 38.3 (6-88) months. Recurrence was detected in 26 patients (5.1%) at a median of 18.9months (2.7% pT1a and 12.7% pT1b). The estimated 5-year cumulative incidence of recurrence for unifocal pT1a lesions was 2.7%. On multivariable analysis, stage higher than pT1a (HR, 5.56 [CI. 2.57-12.0]) and the presence of multifocal or bilateral tumors (HR, 3.32 [CI, 1.45-7.61]) were independent predictors of disease recurrence. For the entire cohort, recurrence was observed in only 10 patients beyond 24months including only 2cases with pT1a. Current guidelines adequately capture most clinically significant recurrences, and with longer follow-up, it may be possible to confirm that routine surveillance beyond 2years may have little clinical significance for patients with asymptomatic unifocal pT1a.

The association of very low PSA with increased cancer-specific death in men with high-grade prostate cancer.

62 Background: It has been hypothesized that very low PSAs in men with high-grade prostate cancer could reflect dedifferentiation and a poorer prognosis, but clinical evidence to support this is limited. We sought to determine whether a very low-presenting PSA was associated with greater prostate cancer-specific mortality (PCSM) among men with Gleason score (GS) 8-10 disease. Methods: The Surveillance, Epidemiology and End Results Program was used to identify a national cohort of 328,904 men diagnosed with cT1-4N0M0 prostate cancer between 2004 and 2010. Multivariable Fine-Gray competing-risks regression analysis was used to determine PCSM as a function of PSA level (&lt;2.5 ng/mL, 2.6-4 ng/mL, 4.1-10 ng/mL, 10.1-20 ng/mL, 20.1-40 ng/mL, or &gt;40ng/mL) and GS (8-10 vs. &lt;=7). Results: Median follow-up was 38 months. Among men with GS 8-10 disease, using PSA 4.1-10 as the reference group, the Adjusted HR (AHR) for PCSM for men with PSA level &lt;2.5 was 1.86 (95% CI 1.51-2.29; P&lt;0.001), PSA 2.6-4 was1.44 (1.17-1.78; P&lt;0.001), PSA 10.1-20 was 1.58 (1.39-1.78; P&lt;0.001), PSA 20.1-40 was 2.04 (1.78-2.33; P&lt;0.001), and PSA&gt;40 was 3.19 (2.83-3.59; P&lt;0.001), suggesting a U-shaped distribution. There was a significant interaction between PSA level and GS (Pinteraction&lt;0.001) such that PSA &lt;2.5 only significantly predicted for poorer PCSM among patients with high grade GS 8-10 disease. Conclusions: Among patients with high grade GS 8-10 disease, patients with PSA &lt;2.5 and 2.6-4 appear to have a higher risk for cancer-specific death compared to patients with a 10.1-20 PSA level, supporting the notion that low PSA in GS 8-10 disease may be a sign of underlying aggressive and extremely poorly differentiated or anaplastic low PSA-producing tumors. Patients with low PSA GS 8-10 disease should be considered for clinical trials studying the use of chemotherapy and other novel agents in very-high risk prostate cancers.

Biological significance of HLA locus matching in unrelated donor bone marrow transplantation

AbstractWe hypothesized that the compatibility of each HLA loci between donor and patient induced divergent transplant-related immunologic responses, which attributed to the individualized manifestation of clinical outcomes. Here, we analyzed 7898 Japanese pairs transplanted with T-cell–replete marrow from an unrelated donor with complete HLA allele typing data. Multivariable competing risk regression analyses were conducted to evaluate the relative risk (RR) of clinical outcomes after transplantation. A significant RR of HLA allele mismatch compared with match was seen with HLA-A, -B, -C, and -DPB1 for grade III-IV acute graft-versus-host disease (GVHD), and HLA-C for chronic GVHD. Of note, only HLA-C and HLA-DPB1 mismatch reduced leukemia relapse, and this graft-versus-leukemia effect of HLA-DPB1 was independent of chronic GVHD. HLA-DRB1 and HLA-DQB1 double (DRB1_DQB1) mismatch was revealed to be a significant RR for acute GVHD and mortality, whereas single mismatch was not. Thus, the number of HLA-A, -B, -C, -DPB1, and DRB1_DQB1 mismatches showed a clear-cut risk difference for acute GVHD, whereas the number of mismatches for HLA-A, -B, -C, and DRB1_DQB1 showed the same for mortality. In conclusion, we determined the biological response to HLA locus mismatch in transplant-related immunologic events, and provide a rationale for use of a personalized algorithm for unrelated donor selection.

A Novel Prognostic Nomogram Accurately Predicts Hepatocellular Carcinoma Recurrence after Liver Transplantation: Analysis of 865 Consecutive Liver Transplant Recipients

Although radiologic size criteria (Milan/University of California, San Francisco [UCSF]) have led to improved outcomes after liver transplantation (LT) for hepatocellular carcinoma (HCC), recurrence remains a significant challenge. We analyzed our 30-year experience with LT for HCC to identify predictors of recurrence. A novel clinicopathologic risk score and prognostic nomogram predicting post-transplant HCC recurrence was developed from a multivariate competing-risk Cox regression analysis of 865 LT recipients with HCC between 1984 and 2013. Overall patient and recurrence-free survivals were 83%, 68%, 60% and 79%, 63%, and 56% at 1-, 3-, and 5-years, respectively. Hepatocellular carcinoma recurred in 117 recipients, with a median time to recurrence of 15 months, involving the lungs (59%), abdomen/pelvis (38%), liver (35%), bone (28%), pleura/mediastinum (12%), and brain (5%). Multivariate predictors of recurrence included tumor grade/differentiation (G4/poor diff hazard ratio [HR] 8.86; G2-3/mod-poor diff HR 2.56), macrovascular (HR 7.82) and microvascular (HR 2.42) invasion, nondownstaged tumors outside Milan criteria (HR 3.02), nonincidental tumors with radiographic maximum diameter ≥ 5 cm (HR 2.71) and <5 cm (HR 1.55), and pretransplant neutrophil-to-lymphocyte ratio (HR 1.77 per log unit), maximum alpha fetoprotein (HR 1.21 per log unit), and total cholesterol (HR 1.14 per SD). A pretransplantation model incorporating only known radiographic and laboratory parameters had improved accuracy in predicting HCC recurrence (C statistic 0.79) compared with both Milan (C statistic 0.64) and UCSF (C statistic 0.64) criteria alone. A novel clinicopathologic prognostic nomogram included explant pathology and had an excellent ability to predict post-transplant recurrence (C statistic 0.85). In the largest single-institution experience with LT for HCC, excellent long-term survival was achieved. Incorporation of routine pretransplantation biomarkers to existing radiographic size criteria significantly improves the ability to predict post-transplant recurrence, and should be considered in recipient selection. A novel clinicopathologic prognostic nomogram accurately predicts HCC recurrence after LT and may guide frequency of post-transplantation surveillance and adjuvant therapy.

Are Biochemical Recurrence Outcomes Similar After Radical Prostatectomy and Radiation Therapy? Analysis of Prostate Cancer–Specific Mortality by Nomogram-predicted Risks of Biochemical Recurrence

BackgroundDue to the protracted natural history of the clinical progression of prostate cancer, biochemical recurrence (BCR) is often used to compare treatment modalities. However, BCR definitions and posttreatment prostate-specific antigen kinetics vary considerably among treatments, calling into the question the validity of such comparisons. ObjectiveTo analyze prostate cancer–specific mortality (PCSM) according to treatment-specific nomogram-predicted risk of BCR for men treated by radical prostatectomy (RP), external-beam radiation therapy (EBRT), and brachytherapy. Design, setting, and participantsA total of 13 803 men who underwent RP, EBRT, or brachytherapy at two US high-volume hospitals between 1995 and 2008. InterventionRP, EBRT, and brachytherapy. Outcome measurements and statistical analysisThe 5-yr progression-free probability (5Y-PFP) was calculated for each patient based on the treatment received using a validated treatment-specific nomogram. Fine and Gray competing risk analysis was then used to estimate PCSM by a patient's predicted 5Y-PFP. Multivariable competing risk regression analysis was used to determine the association of treatment with PCSM after adjusting for nomogram-predicted 5Y-PFP. Results and limitationsMen receiving EBRT had higher 10-yr PCSM compared with those treated by RP across the range of nomogram-predicted risks of BCR: 5Y-PFP >75%, 3% versus 0.9%; 5Y-PFP 51–75%, 6.8% versus 5.9%; 5Y-PFP 26–50%, 12.2% versus 10.6%; and 5Y-PFP ≤25%, 26.6% versus 21.2%. After adjusting for nomogram-predicted 5Y-PFP, EBRT was associated with a significantly increased PCSM risk compared with RP (hazard ratio: 1.5; 95% confidence interval, 1.1–2.0; p=0.006). No statistically significant difference in PCSM was observed between patients treated by brachytherapy and RP, although patient selection factors and lack of statistical power limited this analysis. ConclusionsEBRT patients with similar nomogram-predicted 5Y-PFP appear to have a significantly increased risk of PCSM compared with those treated by RP. Comparison of treatments using nomogram-predicted BCR end points may not be valid. Patient summaryBiochemical recurrence (BCR) outcomes after external-beam radiation therapy and radical prostatectomy are associated with different risks of subsequent prostate cancer–specific mortality. Physicians and patients should cautiously interpret BCR end points when comparing treatments to make treatment decisions.

Abstract MP09: Deep Terminal Negativity of the P Wave in V1 is Associated with Sudden Cardiac Death in the Community: The Atherosclerosis Risk in Communities Study

Background: Deep terminal negativity of the P wave in V1 (P prime in V1, PPV1) defined as PPV1 ≤ -0.1mV in amplitude and ≥40 ms in duration (one small box on ECG grid) is sign of a left atrium enlargement, and a component in the Romhilt-Estes score of left ventricular hypertrophy (LVH). LVH is known to be associated with the risk of sudden cardiac death (SCD). Deep PPV1 negativity is also associated with atrial fibrillation (AF) and stroke; both have been linked to SCD as well. However, it is unknown whether or not PPV1 negativity is independently associated with SCD. Method: Baseline resting digital 12-lead ECGs of 13232 ARIC cohort participants (mean age 53.9±5.7 y; 5760 [43.5%] men; 9747 [73.7%] white) were analyzed. Individuals with prevalent baseline coronary heart disease (CHD), heart failure (HF), or QRS ≥ 120 ms were excluded. The ECGs were analyzed using a 12SL TM algorithm (GE Healthcare, Wauwatosa, WI, USA). Amplitude and duration of PPV1 was automatically measured. Results: Deep PPV1 negativity was observed in 97 (0.73%) participants. During a median follow-up of 14 years, 182 participants had SCD. In multivariable competing risks regression analysis, deep PPV1 negativity was significantly associated with SCD after adjustment for baseline risk factors of CHD and SCD (age, sex, race, diabetes, smoking, alcohol consumption, cholesterol, triglycerides, body mass index, serum creatinine, albumin, systolic blood pressure, use of antihypertensive, QT-prolonging medications, level of physical activity, mean heart rate, QTc, QRS duration, ECG-LVH by Cornell product), and incident HF, AF, stroke [subHR 3.8 (95%CI 1.88-7.69); P&lt;0.0001]. Deep PPV1 negativity showed 7% sensitivity and 99% specificity for SCD prediction. Conclusion: In apparently CV healthy, middle-aged individuals, deep terminal negativity of P-wave in V1 is associated with about 4-times higher risk of SCD during 14 years of follow-up. Further studies should explore the cardiac substrate underlying presence of this marker and its use for risk stratification.

Might Men Diagnosed with Metastatic Prostate Cancer Benefit from Definitive Treatment of the Primary Tumor? A SEER-Based Study

BackgroundFew data exist regarding the impact on survival of definitive treatment of the prostate in men diagnosed with metastatic prostate cancer (mPCa). ObjectiveTo evaluate the survival of men diagnosed with mPCa based on definitive treatment of the prostate. Design, setting, and participantsMen with documented stage IV (M1a–c) PCa at diagnosis identified using Surveillance Epidemiology and End Results (SEER) (2004–2010) and divided based on definitive treatment of the prostate (radical prostatectomy [RP] or brachytherapy [BT]) or no surgery or radiation therapy (NSR). Outcome measurements and statistical analysisKaplan-Meier methods were used to calculate overall survival (OS). Multivariable competing risks regression analysis was used to calculate disease-specific survival (DSS) probability and identify factors associated with cause-specific mortality (CSM). Results and limitationsA total of 8185 patients were identified: NSR (n=7811), RP (n=245), and BT (n=129). The 5-yr OS and predicted DSS were each significantly higher in patients undergoing RP (67.4% and 75.8%, respectively) or BT (52.6 and 61.3%, respectively) compared with NSR patients (22.5% and 48.7%, respectively) (p<0.001). Undergoing RP or BT was each independently associated with decreased CSM (p<0.01). Similar results were noted regardless of the American Joint Committee on Cancer (AJCC) M stage. Factors associated with increased CSM in patients undergoing local therapy included AJCC T4 stage, high-grade disease, prostate-specific antigen ≥20 ng/ml, age ≥70 yr, and pelvic lymphadenopathy (p<0.05). The major limitation of this study was the lack of variables from SEER known to influence survival of patients with mPCa, including treatment with systemic therapy. ConclusionsDefinitive treatment of the prostate in men diagnosed with mPCa suggests a survival benefit in this large population-based study. These results should serve as a foundation for future prospective trials. Patient summaryWe used a large population-based cancer database to examine survival in men diagnosed with metastatic prostate cancer (mPCa) undergoing definitive therapy for the prostate. Local therapy (LT) appeared to confer a survival benefit. Therefore, we conclude that prospective trials are needed to further evaluate the role of LT in mPCa.

1678 PARTIAL NEPHRECTOMY IS NOT ASSOCIATED WITH AN OTHER-CAUSE MORTALITY BENEFIT IN PATIENTS AGED ≥75 YEARS AND/OR MULTIPLE COMORBIDITIES WITH SMALL RENAL MASSES

You have accessJournal of UrologyKidney Cancer: Localized IV1 Apr 20121678 PARTIAL NEPHRECTOMY IS NOT ASSOCIATED WITH AN OTHER-CAUSE MORTALITY BENEFIT IN PATIENTS AGED ≥75 YEARS AND/OR MULTIPLE COMORBIDITIES WITH SMALL RENAL MASSES Maxine Sun, Marco Bianchi, Quoc-Dien Trinh, Jens Hansen, Nawar Hanna, Zhe Tian, Shahrokh Shariat, Paul Perrotte, and Pierre Karakiewicz Maxine SunMaxine Sun Montreal, Canada More articles by this author , Marco BianchiMarco Bianchi Milan, Italy More articles by this author , Quoc-Dien TrinhQuoc-Dien Trinh Detroit, MI More articles by this author , Jens HansenJens Hansen Hamburg, Germany More articles by this author , Nawar HannaNawar Hanna Montreal, Canada More articles by this author , Zhe TianZhe Tian Montreal, Canada More articles by this author , Shahrokh ShariatShahrokh Shariat New York, NY More articles by this author , Paul PerrottePaul Perrotte Montreal, Canada More articles by this author , and Pierre KarakiewiczPierre Karakiewicz Montreal, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1551AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Partial nephrectomy (PN) may protect against other-cause mortality (OCM) relative to radical nephrectomy (RN) in patients with localized renal cell carcinoma (RCC). However, this benefit may not be applicable to patients with advanced age and/or multiple baseline comorbidities. We sought to quantify the effect of treatment type on OCM amongst patients with these characteristics. METHODS Using the Surveillance, Epidemiology, and End Results Medicare-linked database, respectively 8736 (88%) and 1249 (12%) RN and PN patients with T1 RCC were identified (1988–2005). To adjust for inherent differences between treatment types, propensity-based matched analyses was performed. Univariable and multivariable competing-risks regression analyses for prediction of OCM were performed according to treatment type. Sub-analyses were conducted in patients aged >75 years and with >2 comorbidities. RESULTS Following propensity-based matched analyses, the 2- and 5-year OCM rates were 6.2 and 18.8% for RN vs. 6.1 and 17.3% for PN, respectively (P=0.28). Amongst patients aged >75 years, the 2- and 5-year OCM rates were 9.0 and 26.0% for RN vs. 9.7 vs. 27.7% for PN, respectively (P=0.42). For the same time points, in patients with >2 baseline comorbidities, the rates were 8.0 and 23.5% for RN vs. 7.5 and 20.2% for PN, respectively (P=0.19). Following adjustment for all covariates, no difference was recorded between PN and RN in the risk of OCM in the matched population (hazard ratio [HR] %0.92, 95% confidence interval [CI]: 0.79–1.06, P=0.25). Amongst patients aged >75 years (HR: 1.17, 95% CI: 0.94–1.48, P=0.16) and >2 baseline comorbidities (HR: 0.89, 95% CI: 0.75–1.05, P=0.17), no difference was recorded for treatment type. CONCLUSIONS While nephron-sparing has been associated with a protective effect on OCM, some elderly patients and/or those with multiple comorbidities at baseline may not benefit from PN. Amongst these patients, alternative treatment options may be recommended. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e678 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Maxine Sun Montreal, Canada More articles by this author Marco Bianchi Milan, Italy More articles by this author Quoc-Dien Trinh Detroit, MI More articles by this author Jens Hansen Hamburg, Germany More articles by this author Nawar Hanna Montreal, Canada More articles by this author Zhe Tian Montreal, Canada More articles by this author Shahrokh Shariat New York, NY More articles by this author Paul Perrotte Montreal, Canada More articles by this author Pierre Karakiewicz Montreal, Canada More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

249 A non-cancer related survival benefit is associated with partial nephrectomy

Background: Partial nephrectomy (PN) may better protect against other-cause mortality (OCM) when compared with radical nephrectomy (RN) in patients with localized renal cell carcinoma (RCC). Objective: Test the effect of treatment type on OCM. Design, setting, and participants: Using the Surveillance Epidemiology and End Results– Medicare-linked database, 4956 RN patients (82%) and 1068 PN patients (18%) with T1a RCC were identified (1988–2005). Measurements: To adjust for inherent differences between treatment types, we relied on propensity-matched analyses. One-to-one matching was performed according to age, sex, race, baseline Charlson comorbidity index (CCI), baseline diagnosis of hypercalcemia and hyperlipidemia, socioeconomic status (SES), population density, tumor size, and year of surgery. The 2- and 5-yr OCM rates were computed using cumulative incidence. Univariable and multivariable competing-risks regression analyses for prediction of OCM were performed according to treatment type. Adjustment was made for cancerspecific mortality (CSM), patient age, CCI, sex, race, SES, tumor grade, and year of surgery. Results and limitations: Following propensity-based matching, 1068 RN patients were matched with 1068 PN patients. The 2- and 5-yr OCM rates after nephrectomy were 5.0% and 16.0% for PN versus 6.9% and 18.1% for RN, respectively. In the postpropensity multivariable analyses, patients who underwent PN were significantly less likely to die of OCM compared with their RN-treated counterparts (hazard ratio [HR]: 0.83; 95% confidence interval, 0.69–0.98; p = 0.04). Increasing age (HR: 1.08, p < 0.001), higher CCI (HR: 1.14, p < 0.001), female gender (HR: 0.79, p = 0.02), baseline hypercalcemia (HR: 2.05, p = 0.03), baseline hyperlipidemia (HR: 0.73, p = 0.003), and year of surgery (HR: 0.95, p = 0.003) were independent predictors of OCM. Conclusions: Compared with PN-treated patients, RN-treated patients are more likely to die of OCM after surgery, even after adjusting for CSM, as well as baseline CCI. Consequently, PN should be offered whenever technically feasible.