Pretreatment Risk Stratification Research Articles

A combination of computer extracted measurements of prostate capsule shape and tumor texture on MRI to predict biochemical recurrence post treatment.

e16554 Background: Prostate cancer (PCa) biochemical recurrence (BCR) occurs in a significant proportion of men after treatment and is associated with increased mortality. Identifying PCa patients at risk of BCR following definitive therapy may help identify patients who might benefit from adjuvant therapy. Multi-parametric MRI (mpMRI) is being increasingly used in pre-treatment staging and risk stratification of PCa. In this work, we sought to explore whether a combination of computer extracted features relating to prostate capsule shape and tumor texture from pre-treatment mpMRI is predictive of BCR post treatment. Methods: This single center and retrospective study included 80 men with PCa who underwent pre-treatment 3T mpMRI and were followed for > 3 years post treatment. These men were grouped into a training set D1 (N = 50, 25 each of BCR+ and BCR-) and an independent validation set D2 (N = 30, 10 BCR+ and 20 BCR-). The prostate capsule and cancer region of interest (ROI) were annotated on mpMRI by a single experienced radiologist. Shape features (curvature and orientation) were extracted from a surface of interest where statistically significant differences were observed between BCR+ and BCR- patients in the training set. Radiomic features for capturing tumor textural patterns (including 1st and 2nd order statistics, Gabor and Haralick) were extracted from within the radiologist annotated cancer ROIs. Features from D1 were used to train random forest classifiers, one each with shape (Cs) and radiomic (CR) features. A fused Bayesian classifier (CR+S) was created by integrating decisions from both Cs and CR. Results: The classifiers Cs, CR and CR+S were evaluated on independent validation set D2, resulting in area under the curve (AUCs) of 0.71, 0.81 and 0.84 respectively. Cs added value in patients who had extra prostatic spread of PCa, but suffered from mpMRI intensity artefacts that affected performance of CR. Conclusions: Integrating prostate capsule shape and tumor radiomic features from pre-treatment mpMRI enabled prediction of PCa BCR after treatment. Multi-site validation is needed to establish the robustness of the approach.

MP78-14 IMPORTANCE OF TUMOR SIZE AS RISK STRATIFICATION PARAMETER IN UPPER TRACT UROTHELIAL CARCINOMA (UTUC)

You have accessJournal of UrologyBladder Cancer: Upper Tract Transitional Cell Carcinoma II1 Apr 2017MP78-14 IMPORTANCE OF TUMOR SIZE AS RISK STRATIFICATION PARAMETER IN UPPER TRACT UROTHELIAL CARCINOMA (UTUC) Beat Foerster, Thomas Seisen, Marco Bandini, Kees Hendricksen, Anna K. Czech, Marco Moschini, Mohammad Abufaraj, Marco Bianchi, Donald Schweitzer, Kilian M. Gust, Morgan Roupret, Alberto Briganti, Bas G. van Rhijn, Piotr Chlosta, Pierre Colin, Hubert John, and Shahrokh F. Shariat Beat FoersterBeat Foerster More articles by this author , Thomas SeisenThomas Seisen More articles by this author , Marco BandiniMarco Bandini More articles by this author , Kees HendricksenKees Hendricksen More articles by this author , Anna K. CzechAnna K. Czech More articles by this author , Marco MoschiniMarco Moschini More articles by this author , Mohammad AbufarajMohammad Abufaraj More articles by this author , Marco BianchiMarco Bianchi More articles by this author , Donald SchweitzerDonald Schweitzer More articles by this author , Kilian M. GustKilian M. Gust More articles by this author , Morgan RoupretMorgan Roupret More articles by this author , Alberto BrigantiAlberto Briganti More articles by this author , Bas G. van RhijnBas G. van Rhijn More articles by this author , Piotr ChlostaPiotr Chlosta More articles by this author , Pierre ColinPierre Colin More articles by this author , Hubert JohnHubert John More articles by this author , and Shahrokh F. ShariatShahrokh F. Shariat More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2102AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES One of the major challenges regarding upper tract urothelial carcinoma (UTUC) is to identify patients who can safely be managed by kidney-sparing surgery (KSS). European Association of Urology (EAU) Guidelines proposed criteria for pre-treatment risk stratification includes a tumor diameter >1cm as exclusion criteria for KSS. Our aim was to evaluate the performance of different tumor diameters for identifying advanced pathologic stage after RNU and to assess its prognostic value on survival. METHODS A multi-institutional retrospective study was conducted that included 800 patients undergoing radical nephroureterectomy (RNU) for non-metastatic UTUC between 1988 and 2016. Tumor sizes were pathologically assessed and categorized into four groups: ≤1, 1.1-2, 2.1-3, >3 cm. We performed logistic regression analyses to compare different diameter thresholds in predicting advanced pathologic stage. Kaplan-Meier analyses with log rank test for comparison was used for the estimation of survival outcomes. RESULTS Overall, 31 (3.9%) patients had a tumor size ≤1cm, 107 (13.4%) 1.1-2cm, 175 (21.9%) 2.1-3cm and 487 (60.9%) >3cm. In preoperative predictive models, that adjusted for the effects of clinicopathologic features, tumor diameters >2cm versus ≤2cm (OR 1.90, p=0.011) and >3cm versus ≤3 (OR 1.71, p=0.003), were both independently associated with advanced stage (≥pT2). The addition of tumor size improved the accuracy of the model from 59 to 61 %. Previous bladder cancer (p=0.011) and preoperative hydronephrosis (p=0.015) were also associated with ≥pT2 disease. Tumor sizes >2cm or ≤2cm predicted muscle-invasion (≥pT2) with 57% positive predictive value (PPV) and 59% negative predictive value (NPV), respectively. With a threshold of 3cm the PPV was 59% and NPV 54%. Kaplan-Meier curves did not show a prognostic impact of tumor size on recurrence-free and cancer-specific survival after RNU. CONCLUSIONS Tumor size of 2cm seems to best identify patients who likely harbor muscle-invasive tumor stage. This puts the current risk stratification of EAU Guidelines based on 1cm into question. Our study is limited by the small sample size of ≤1cm tumors and its design (RNU cohort, retrospective, multi-institutional). Therefore, this area needs further research to better identify the optimal criteria for KSS. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1036-e1037 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Beat Foerster More articles by this author Thomas Seisen More articles by this author Marco Bandini More articles by this author Kees Hendricksen More articles by this author Anna K. Czech More articles by this author Marco Moschini More articles by this author Mohammad Abufaraj More articles by this author Marco Bianchi More articles by this author Donald Schweitzer More articles by this author Kilian M. Gust More articles by this author Morgan Roupret More articles by this author Alberto Briganti More articles by this author Bas G. van Rhijn More articles by this author Piotr Chlosta More articles by this author Pierre Colin More articles by this author Hubert John More articles by this author Shahrokh F. Shariat More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

A stiff extracellular matrix is associated with malignancy in peripheral neuroblastic tumors.

Improved prognosis for patients with peripheral neuroblastic tumors (PNB) depends on enhanced pretreatment risk stratification combined with research into new therapeutic targets. This study investigated the potential contribution of extracellular matrix (ECM) elements toward this endeavor. We characterized certain elements such as reticulin fibers, collagen type I fibers, and elastic fibers by digital pathology in almost 400 untreated PNB. A reticular and poorly porous ECM was identified in neuroblastomas (NBs) from patients with clinical and biological features associated with poor prognosis compared with a loose and permeable matrix found in NBs of the favorable cohort. Aggressiveness patterns of ECM can be accurately determined by morphometric tools and could become candidate elements for novel therapies.

The prognostic value of preoperative serum albumin-globulin ratio for high-grade bladder urothelial carcinoma treated with radical cystectomy: A propensity score-matched analysis.

Albumin-globulin ratio (AGR) has been reported as an independent risk factor for survival outcomes of a variety of malignancies. We aimed to further examine the prognostic value of AGR for urothelial carcinoma of bladder (UCB) using a propensity score-matched (PSM) analysis. The medical data of 189 high-grade UCB patients undergoing radical cystectomy were retrospectively reviewed. AGR was defined as the ratio of serum albumin to nonalbumins (serum total protein-albumin). The association of preoperative AGR with clinicopathologic characteristics and prognosis were assessed. Multivariate analyses using Cox regression models were applied to evaluate the independent prognostic factors. The receiver operating curve analysis indicated 1.55 as the optimal cutoff value to define low or high AGR. In prematched cohorts, Kaplan-Meier analysis indicated that AGR lower than 1.55 was associated with poorer overall survival (OS), progression-free survival (PFS), and tumor-specific survival (TSS) (P < 0.001 for all). Multivariable cox analyses also showed that AGR lower than 1.55 were an independent risk factor for survival outcomes, including OS, PFS, and TSS (P < 0.01 for all). In particular, AGR lower than 1.55 remained its prognostic value after PSM analysis. Low AGR was a significant unfavorable factor for UCB patients treated with radical cystectomy. This viable parameter should be enrolled in the pretreatment risk stratification for UCB.

Primary central nervous system lymphoma: a new prognostic model for patients with diffuse large B-cell histology.

BackgroundAge and performance status are important prognostic factors in primary central nervous system (CNS) lymphoma. Although several prognostic models have been proposed, there is no consensus on the optimal model for patients with diffuse large B-cell histology.MethodsSeventy-seven patients with primary CNS diffuse large B-cell lymphoma were retrospectively analyzed to determine factors affecting survival. Three Western models were applied to our eligible patients; we devised a novel model based on our findings.ResultsThe median patient age was 59 years (range, 29–77); the median event-free and overall survival (OS) durations were 35.9 and 12.6 months, respectively. Nottingham/Barcelona and Memorial Sloan Kettering Cancer Center models were applicable to our cohorts. Multivariate analysis showed that advanced age, multifocal lesions, and high cerebrospinal fluid (CSF) protein concentrations were correlated significantly. A novel model for predicting prognosis was then developed based on these variables. Each variable was assigned 1 point; patients with a total score of 0, 1, 2, and 3 were categorized into the low- (N=17), moderate- (N=26), high- (N=14), and very high-risk groups (N=4), respectively. Sixty-one patients were eligible considering our model; the median OS was 58.2, 34.8, 9.0, and 1.8 months in the low-, moderate-, high-, and very high-risk groups, respectively (P<0.01).ConclusionAdvanced age, multifocal lesions, and high CSF protein concentration were adversely related with prognosis. Our model can be helpful in pre-treatment risk stratification for patients with primary CNS lymphoma with diffuse large B-cell histology.

Novel concepts for risk stratification in prostate cancer.

Since Partin introduced the analysis of prostate-specific antigen, clinical T-stage and Gleason scores to estimate the risk of progression in men with localised prostate cancer, our understanding of factors that modify this risk has changed drastically. There are now multiple risk stratification tools available, including look-up tables, risk stratification/classification analyses, regression-tree analyses, nomograms and artificial neural networks. Concurrently, descriptions of novel biopsy strategies, imaging modalities and biomarkers are frequently published with the aim of improving risk stratification. With an abundance of new information available, incorporating advances into clinical practice can be confusing. This article aims to outline the major novel concepts in prostate cancer risk stratification for men with biopsy confirmed prostate cancer. We will detail which of these novel techniques and tools are likely to be adopted to aid treatment decisions and enable more accurate post-diagnosis, pretreatment risk stratification.

Combined Pretreatment Serum Testosterone Concentration and Risk Stratification Enhances Interpretation of Prostate-Specific Antigen (PSA) Kinetics in Localized Prostate Cancer After Stereotactic Body Radiation Therapy (SBRT)

Combined Pretreatment Serum Testosterone Concentration and Risk Stratification Enhances Interpretation of Prostate-Specific Antigen (PSA) Kinetics in Localized Prostate Cancer After Stereotactic Body Radiation Therapy (SBRT)

A 30 gene panel as prognostic for survival outcomes in clinically resectable gastric cancer.

4039Background: Current pre-treatment risk stratification modalities for gastric cancer (GC) are inadequate. Methods: Somatic mutation data from 19 cancer types sequenced by The Cancer Genome Atlas...

Vascular patterns provide therapeutic targets in aggressive neuroblastic tumors.

Angiogenesis is essential for tumor growth and metastasis, nevertheless, in NB, results between different studies on angiogenesis have yielded contradictory results. An image analysis tool was developed to characterize the density, size and shape of total blood vessels and vascular segments in 458 primary neuroblastic tumors contained in tissue microarrays. The results were correlated with clinical and biological features of known prognostic value and with risk of progression to establish histological vascular patterns associated with different degrees of malignancy. Total blood vessels were larger, more abundant and more irregularly-shaped in tumors of patients with associated poor prognostic factors than in the favorable cohort. Tumor capillaries were less abundant and sinusoids more abundant in the patient cohort with unfavorable prognostic factors. Additionally, size of post-capillaries & metarterioles as well as higher sinusoid density can be included as predictive factors for survival. These patterns may therefore help to provide more accurate pre-treatment risk stratification, and could provide candidate targets for novel therapies.

Risk-Adapted Induction and Maintenance with Ofatumumab in Previously Untreated Patients with Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)

Introduction: Pre-treatment cytogenetics and post-treatment minimal residual disease (MRD) status are predictive biomarkers in CLL. We hypothesized the two markers can guide a risk-adapted treatment strategy to achieve deep and durable responses in previously untreated CLL/SLL.Methods and Patients: 31 subjects were enrolled. Risk assessment was performed before treatment and after induction. Based on pre-treatment FISH, patients were categorized into either high-risk (with deletion 17p or 11q) or standard-risk (no deletion 17p or 11q) and treated with up to 6 cycles of OFC (Ofatumumab 300mg i.v. on cycle 1 day 1, 1000mg i.v. on cycle 1 day 8 and on day 1 of subsequent cycles; Fludarabine 25mg/m2 i.v. on day 1-3; Cyclophosphamide 250mg/m2 i.v. on day 1-3;) or OF (Ofatumumab given as described for the high-risk group; Fludarabine 25mg/m2 /d i.v. on day 1-5), respectively. Three months after completion of chemoimmunotherapy, a second risk stratification was performed based on presence or absence of MRD. MRD negative (MRDneg) state was defined as <1 monoclonal B cell among 104 leukocytes based on 8-color peripheral blood flow cytometry (PBFC). MRDneg patients were observed and MRD positive (MRDpos) patients received ofatumumab maintenance (1000mg i.v. every two months for 4 cycles). Serial PBFCs were performed pre- and post-induction, pre- and post-maintenance, and at 24 months. The primary endpoint was progression free survival at 24 months.Results: 25 patients who completed ≥3 cycles of chemoimmunotherapy were considered evaluable; median age 60 years (range 26-79), 56% male, 48% in high Rai stage, 68.6% having unmutated IGHV. Nine (36%) patients received OFC, 16 (64%) received OF. 72% of all patients required dose reductions and 64% completed 6 cycles. After induction, 15 (60%) patients were MRDpos and received maintenance, while 10 MRDneg patients were observed. More patients on the OFC arm were MRDneg than on the OF arm (66.7 vs. 25%, P =0.087). At a median follow-up of 32 months, 7 patients had progressed. The projected PFS was 95% at 24 months (85-100%), 82.5% at 32 months (66-100%), and 75% at 36 months (56-100%), with no significant difference between subgroups divided by treatment regimen or MRD status after induction. The estimated median PFS was 36 months for MRDpos vs. 49 months for MRDneg patients (P =0.13). At 24 months, 3 out of 7 MRDneg patients maintained MRD negativity without further treatment. For MRDpos patients, the number of residual CLL cells appeared to decrease during maintenance ofatumumab and two patients became transiently MRDneg. However, the change in MRD burden was not statistically significant (median CLL cell count per 104 leukocytes: 50 vs. 36 at pre- vs. post-maintenance, P =0.13) and none of the patients receiving maintenance was MRDneg at 24 months. The median CLL count per 104 leukocytes increased from 36 at post-maintenance to 260 at 24 months (P =0.047). Taken together, MRD after chemoimmunotherapy was not eradicated with additional doses of ofatumumab. We hypothesized that loss of CD20 expression through trogocytosis (Fc-receptor mediated "stripping" of CD20 from CLL cells) or internalization may limit the efficacy of ofatumumab. In fact, among MRDpos patients, CD20 expression was negative by PBFC in 90% of patients at post-induction and in all patients at post-maintenance. On bone marrow biopsies, immunohistochemical staining for CD20 using an antibody against an intracellular epitope confirmed CD20 loss or demonstrated substantially decreased CD20 expression compared to matching baseline samples.Conclusion: Pre-treatment risk stratification with FISH cytogenetics can guide the choice of induction therapy. Maintenance therapy with four additional doses of ofatumumab in MRDpos patients did not improve the depth of response but appeared to reduce the risk of disease progression. Loss of CD20 expression on residual tumor cells may limit the efficacy of prolonged therapy with an anti-CD20 monoclonal antibody. DisclosuresWiestner:Pharmacyclics: Research Funding.

TH and DCX mRNAs in peripheral blood and bone marrow predict outcome in metastatic neuroblastoma patients.

In metastatic neuroblastoma (NB) patients, accurate risk stratification and disease monitoring would reduce relapse probabilities. This study aims to evaluate the independent prognostic significance of detecting tyrosine hydroxylase (TH) and doublecortin (DCX) mRNAs by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) in peripheral blood (PB) and bone marrow (BM) samples from metastatic NB patients. RT-qPCR was performed on PB and BM samples from metastatic NB patients at diagnosis, post-induction therapy and at the end of treatment for TH and DCX mRNAs detection. High levels of TH and DCX mRNAs when detected in PB and BM at diagnosis independently predicted worse outcome in a cohort of 162 metastatic NB. In the subgroup of high-risk metastatic NB, TH mRNA detected in PB remained as independent predictor of EFS and OS at diagnosis. After the induction therapy, high levels of TH mRNA in PB and DCX mRNA in BM independently predicted poor EFS and OS. Furthermore TH mRNA when detected in BM predicted worse EFS. TH mRNA in PB samples at the end of treatment is an independent predictor of worse outcome. TH and DCX mRNAs levels in PB and BM assessed by RT-qPCR should be considered in new pre-treatment risk stratification strategies to reliable estimate outcome differences in metastatic NB patients. In those high-risk metastatic NB, TH and DCX mRNA quantification could be used for the assessment of response to treatment and for early detection of progressive disease or relapses.

High-dose chemotherapy and autologous haematopoietic stem cell rescue for children with high-risk neuroblastoma.

Despite the development of new treatment options, the prognosis of high-risk neuroblastoma patients is still poor; more than half of patients experience disease recurrence. High-dose chemotherapy and haematopoietic stem cell rescue (i.e. myeloablative therapy) might improve survival. This review is the second update of a previously published Cochrane review.Primary objectiveTo compare the efficacy, that is event-free and overall survival, of high-dose chemotherapy and autologous bone marrow or stem cell rescue with conventional therapy in children with high-risk neuroblastoma. Secondary objectivesTo determine adverse effects (e.g. veno-occlusive disease of the liver) and late effects (e.g. endocrine disorders or secondary malignancies) related to the procedure and possible effects of these procedures on quality of life.We searched the electronic databases The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, issue 11), MEDLINE/PubMed (1966 to December 2014) and EMBASE/Ovid (1980 to December 2014). In addition, we searched reference lists of relevant articles and the conference proceedings of the International Society for Paediatric Oncology (SIOP) (from 2002 to 2014), American Society for Pediatric Hematology and Oncology (ASPHO) (from 2002 to 2014), Advances in Neuroblastoma Research (ANR) (from 2002 to 2014) and American Society for Clinical Oncology (ASCO) (from 2008 to 2014). We searched for ongoing trials by scanning the ISRCTN register (www.isrct.com) and the National Institute of Health Register (www.clinicaltrials.gov). Both registers were screened in April 2015.Randomised controlled trials (RCTs) comparing the efficacy of myeloablative therapy with conventional therapy in high-risk neuroblastoma patients.Two authors independently performed study selection, data extraction and risk of bias assessment. If appropriate, we pooled studies. The risk ratio (RR) and 95% confidence interval (CI) was calculated for dichotomous outcomes. For the assessment of survival data, we calculated the hazard ratio (HR) and 95% CI. We used Parmar's method if hazard ratios were not reported in the study. We used a random-effects model.We identified three RCTs including 739 children. They all used an age of one year as the cut-off point for pre-treatment risk stratification. The first updated search identified a manuscript reporting additional follow-up data for one of these RCTs, while the second update identified an erratum of this study. There was a significant statistical difference in event-free survival in favour of myeloablative therapy over conventional chemotherapy or no further treatment (three studies, 739 patients; HR 0.78, 95% CI 0.67 to 0.90). There was a significant statistical difference in overall survival in favour of myeloablative therapy over conventional chemotherapy or no further treatment (two studies, 360 patients; HR 0.74, 95% CI 0.57 to 0.98). However, when additional follow-up data were included in the analyses the difference in event-free survival remained statistically significant (three studies, 739 patients; HR 0.79, 95% CI 0.70 to 0.90), but the difference in overall survival was no longer statistically significant (two studies, 360 patients; HR 0.86, 95% CI 0.73 to 1.01). The meta-analysis of secondary malignant disease and treatment-related death did not show any significant statistical differences between the treatment groups. Data from one study (379 patients) showed a significantly higher incidence of renal effects, interstitial pneumonitis and veno-occlusive disease in the myeloablative group compared to conventional chemotherapy, whereas for serious infections and sepsis no significant difference between the treatment groups was identified. No information on quality of life was reported. In the individual studies we evaluated different subgroups, but the results were not univocal in all studies. All studies had some methodological limitations.Based on the currently available evidence, myeloablative therapy seems to work in terms of event-free survival. For overall survival there is currently no evidence of effect when additional follow-up data are included. No definitive conclusions can be made regarding adverse effects and quality of life, although possible higher levels of adverse effects should be kept in mind. A definitive conclusion regarding the effect of myeloablative therapy in different subgroups is not possible. This systematic review only allows a conclusion on the concept of myeloablative therapy; no conclusions can be made regarding the best treatment strategy. Future trials on the use of myeloablative therapy for high-risk neuroblastoma should focus on identifying the most optimal induction and/or myeloablative regimen. The best study design to answer these questions is a RCT. These RCTs should be performed in homogeneous study populations (e.g. stage of disease and patient age) and have a long-term follow-up. Different risk groups, using the most recent definitions, should be taken into account.It should be kept in mind that recently the age cut-off for high risk disease was changed from one year to 18 months. As a result it is possible that patients with what is now classified as intermediate-risk disease have been included in the high-risk groups. Consequently the relevance of the results of these studies to the current practice can be questioned. Survival rates may be overestimated due to the inclusion of patients with intermediate-risk disease.

Review of the development of DNA methylation as a marker of response to neoadjuvant therapy and outcomes in rectal cancer.

There is much debate around the preoperative treatment of colorectal cancer and, in particular, neoadjuvant chemoradiotherapy in locally advanced rectal cancer. This treatment carries a significant risk of harmful side effects and has a highly variable response rate. Predictive biomarkers have been the subject of a great deal of study with the aim of pretreatment risk stratification in order to more accurately determine which patients will derive the most benefit and least harm from these treatments. The study of epigenetics in colorectal cancer is relatively recent, and distinct patterns of aberrant DNA methylation, in particular the cytosine-phosphate-guanine (CpG) island methylator phenotype (CIMP), have been demonstrated in colorectal cancer, and their characterisation and significance are under debate, particularly in rectal cancer. These patterns of DNA methylation have been associated with differences in response to therapy and treatment outcomes and therefore have the potential to be used as biomarkers in tailored therapy regimes for patients with rectal cancer. This review aims to summarise the current state of the art in rectal cancer, with particular regard to the determination of DNA methylation patterns, the CpG island methylator phenotype and its potential as a novel biomarker in rectal cancer treatment and prediction of outcomes and response after neoadjuvant chemoradiotherapy.

Combining Abdominal and Cosmetic Breast Surgery Does Not Increase Short-term Complication Rates: A Comparison of Each Individual Procedure and Pretreatment Risk Stratification Tool

Combined abdominal and breast surgery presents a convenient and relatively cost-effective approach for accomplishing both procedures. This study is the largest to date assessing the safety of combined procedures, and it aims to develop a simple pretreatment risk stratification method for patients who desire a combined procedure. All women undergoing abdominoplasty, panniculectomy, augmentation mammaplasty, and/or mastopexy in the TOPS database were identified. Demographics and outcomes for combined procedures were compared to individual procedures using χ(2) and Student's t-tests. Multiple logistic regression provided adjusted odds ratios for the effect of a combined procedure on 30-day complications. Among combined procedures, a logistic regression model determined point values for pretreatment risk factors including diabetes (1 point), age over 53 (1), obesity (2), and 3+ ASA status (3), creating a 7-point pretreatment risk stratification tool. A total of 58,756 cases met inclusion criteria. Complication rates among combined procedures (9.40%) were greater than those of aesthetic breast surgery (2.66%; P < .001) but did not significantly differ from abdominal procedures (9.75%; P = .530). Nearly 77% of combined cases were classified as low-risk (0 points total) with a 9.78% complication rates. Medium-risk patients (1 to 3 points) had a 16.63% complication rate, and high-risk (4 to 7 points) 38.46%. Combining abdominal and breast procedures is safe in the majority of patients and does not increase 30-day complications rates. The risk stratification tool can continue to ensure favorable outcomes for patients who may desire a combined surgery. 4 Risk.

MP14-19 LYMPH NODE METASTASES IN GLEASON ≤ 6 PROSTATE CANCER: DATA FROM A GERMAN MULTICENTER DATABASE

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History III1 Apr 2015MP14-19 LYMPH NODE METASTASES IN GLEASON ≤ 6 PROSTATE CANCER: DATA FROM A GERMAN MULTICENTER DATABASE Daniel Schindele, Daniel Baumunk, Simon Blaschke, Annette Reinicke, Tom Fischer, Stefan Hinz, Alexander Winter, Mario Zacharias, Sebastian Schäfers, Ulrich Witzsch, Robert Kössler, Jan Fichtner, Steffen Weikert, Kurt Miller, and Martin Schostak Daniel SchindeleDaniel Schindele More articles by this author , Daniel BaumunkDaniel Baumunk More articles by this author , Simon BlaschkeSimon Blaschke More articles by this author , Annette ReinickeAnnette Reinicke More articles by this author , Tom FischerTom Fischer More articles by this author , Stefan HinzStefan Hinz More articles by this author , Alexander WinterAlexander Winter More articles by this author , Mario ZachariasMario Zacharias More articles by this author , Sebastian SchäfersSebastian Schäfers More articles by this author , Ulrich WitzschUlrich Witzsch More articles by this author , Robert KösslerRobert Kössler More articles by this author , Jan FichtnerJan Fichtner More articles by this author , Steffen WeikertSteffen Weikert More articles by this author , Kurt MillerKurt Miller More articles by this author , and Martin SchostakMartin Schostak More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.881AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recent data indicate that lymph node involvement (LNI) in prostate cancer with a Gleason score (GS) 6 or less is very rare. Some authors have concluded that pelvic lymph node dissection can regularly be omitted if the GS of the needle biopsy (NB) specimen is ≤ 6. These data, however, represent results published by only a few selected and highly specialized institutions. Objective of our study was to analyze data from a multicenter cohort regarding the incidence of LNI in GS ≤ 6 prostate cancer. METHODS Data was obtained from the online-database www.prostata-ca.net. All patients who were treated by radical prostatectomy (RP) and had data available on GS of NB and RP specimen were included in the analysis. RESULTS Out of 12759 eligible patients, 8627 were identified as having been treated by RP and PLND in the years 2005 to 2014. Median prostate specific antigen (PSA) was 7.99 ng/ml. Of these patients, 3206 (37.2%) were initially diagnosed with a GS ≤ 6 by NB, whereas only 1758 (20.4%) had a GS ≤ 6 in the RP specimen. LNI was present in 1000 cases (11.6%) overall. Prevalence of LNI in patients with a GS ≤ 6 in the NB specimen was 3.8% (95% confidence interval (CI) 3–5%), compared to 2.3% (95% CI 2–3%) if the GS ≤ 6 was confirmed in the RP specimen. Significant upgrading (GS ≤ 6 to a GS ≥ 7) occurred in 1714 (19.9%) of all cases, thus affecting 53.5% of patients originally diagnosed with a GS ≤ 6. CONCLUSIONS In a large German multicenter cohort, LNI in low grade prostate cancer was rare (2.3%) if a GS ≤ 6 was diagnosed in the RP specimen. 83 out of 123 patients (67%) with lymph node metastases showed a GS ≥ 7 at final diagnosis, but were initially graded as GS ≤ 6 in the NB specimen. Significant undergrading of the NB specimen was common and occurred in half of all patients with a GS ≤ 6 in the biopsy. Our study demonstrates that, especially outside of highly specialized centers, undergrading of NB specimen is still common and the malignant potential of some cancers is thus discovered only after RP and PLND. More reliable tools for pretreatment risk-stratification are warranted. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e158 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Daniel Schindele More articles by this author Daniel Baumunk More articles by this author Simon Blaschke More articles by this author Annette Reinicke More articles by this author Tom Fischer More articles by this author Stefan Hinz More articles by this author Alexander Winter More articles by this author Mario Zacharias More articles by this author Sebastian Schäfers More articles by this author Ulrich Witzsch More articles by this author Robert Kössler More articles by this author Jan Fichtner More articles by this author Steffen Weikert More articles by this author Kurt Miller More articles by this author Martin Schostak More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MR Imaging-Transrectal US Fusion for Targeted Prostate Biopsies: Implications for Diagnosis and Clinical Management.

Cancer of the prostate gland is a common but heterogeneous disease requiring individualized risk stratification for optimal clinical management. However, transrectal ultrasonography (US)-guided biopsy-the standard of care for diagnosis of prostate cancer-frequently fails to detect aggressive tumors or provide reliable parameters for pretreatment risk stratification. Multiparametric magnetic resonance (MR) imaging is the most accurate imaging technique for prostate cancer detection and local staging. Recently, different approaches have been developed to allow targeted biopsies of areas that are suspicious for cancer at MR imaging, including direct MR imaging guidance and MR imaging-transrectal US fusion, which can be achieved with cognitive fusion or software assistance. Regardless of the technique used, targeted prostate biopsies have the potential to increase detection of clinically relevant prostate cancer and provide more reliable risk stratification in patients with known cancer. The authors discuss the shortcomings of traditional diagnostic workup for prostate cancer, the rationale for targeted prostate biopsies, the different techniques available for targeting suspicious areas seen at MR imaging, and the clinical contexts in which targeted prostate biopsies might be useful. In addition, they discuss opportunities and challenges associated with MR imaging-transrectal US fusion biopsy, as well as questions that need to be addressed before formal incorporation of this technique into practice guidelines.

Abstract 18787: Hypertension Treatment and Control Rates in United States Adults by Risk Group

Introduction: Ten-year cardiovascular disease (CVD) risk and absolute benefit from antihypertensive therapy vary at any given BP based on associated risk factor levels. Thus, implications of treatment and control rates at a particular BP vary substantially in different risk groups. Objectives: We examined the prevalence, treatment, and control of hypertension (HTN) by risk group in US adults without prevalent CVD. Methods: We used data from the National Health and Nutrition Examination Survey 2005 to 2010 for adults age 40-79 years without prevalent CVD (n=4,066). We estimated 10-year risk for an atherosclerotic CVD (ASCVD) event using the ACC/AHA 2013 Pooled Cohort risk equations. We examined HTN treatment and control rates according to current guidelines in middle-aged (40-59 years) and older (60-79 years) adults with: 10-year ASCVD risk &lt;7.5% (no diabetes/kidney disease); 10-year ASCVD risk ≥7.5% (no diabetes/kidney disease); and either diabetes or kidney disease. Results: The proportion of adults with treatment-eligible HTN was 39.3% for those with 10-year ASCVD risk &lt;7.5%, 32.2% for those with 10-year ASCVD risk ≥7.5%, and 28.4% for those with either diabetes or kidney disease (see Table 1). Treatment rates across the risk groups varied from 51.5% to 79.0% for middle-aged adults and 81.8% to 90.2% for older adults. HTN control rates were highest (87.7%) in older adults with 10-year ASCVD risk &lt;7.5% but were lowest (29.3%) in middle-aged individuals with 10-year ASCVD risk ≥7.5%. Conclusions: US HTN guidelines, based solely on BP thresholds, identify a higher proportion of low-risk adults and a lower proportion of high-risk adults as being eligible for treatment. Control rates remain suboptimal in high-risk individuals, particularly middle-aged adults. Future guidelines should consider pre-treatment risk stratification to identify those at increased pretreatment ASCVD risk who would benefit most from more intensive therapy.

127IN - Pet-Based Decisions in Hodgkin Lymphoma

ABSTRACT PET/CT has emerged as the most accurate tool for staging, treatment monitoring and response evaluation in Hodgkin lymphoma (HL). Accurate staging and restaging are very important for the optimal management of HL, and PET/CT is the cornerstone of the staging procedures recommended in the recently revised staging and response criteria. More precise determination of disease extent may result in more precise pre-treatment risk stratification, and is also essential to the minimal and highly individualised radiotherapy volumes of the present era. Early PET-response is the strongest predictor final treatment outcome and long-term progression-free and overall survival. The strong prognostic value is demonstrated as early as after one chemotherapy cycle, thus replacing traditional mid-treatment monitoring by in-vivo treatment sensitivity testing. A number of ongoing or recently completed trials investigate the use of PET/CT for early response-adapted therapy, with therapeutic stratification based on interim PET/CT results. The first results from these trials have been mostly encouraging. Post-treatment PET/CT the major determinant of post-treatment response assessment and enables selection of advanced stage patient without need for consolidation radiotherapy. While PET/CT seems to have little or no role in the routine surveillance of HL patients, recent data point toward an important role in the selection of therapy in relapsed and refractory disease, and for PET-response adapted therapy in this setting, as well as in first-line therapy. PET/CT has a large impact on both trial design and on the management of individual patients, so it is necessary also for the clinician to be aware of the strengths and possibilities, but also the important pitfalls and shortcomings of this highly sensitive diagnostic method. Disclosure: M. Hutchings: Advisory board and consultancy: Takeda/Millennium Advisory board: Genentech.

Efficiency of pretreatment risk stratification systems for prostate cancer in a Japanese population treated with radical prostatectomy.

To determine whether the currently available pretreatment risk classification systems are applicable in Japanese prostate cancer patients. Using data obtained from 1264 consecutive patients with prostate cancer treated with radical prostatectomy at four hospitals in Japan, biochemical recurrence-free survival rates were estimated and compared between the D'Amico, the National Institute for Health and Clinical Excellence, the Cancer of the Prostate Strategic Urological Research Endeavor, the National Comprehensive Cancer Network, and the European Society of Medical Oncology risk groups by using the Kaplan-Meier method and log-rank test. The 5-year biochemical recurrence-free survival rates in the D'Amico low-, intermediate-, and high-risk groups were 88.3%, 84.7% and 66.9%, respectively (low and intermediate risk vs high risk, P < 0.001). The 5-year biochemical recurrence-free survival rates in the National Institute for Health and Clinical Excellence, National Comprehensive Cancer Network, and European Society of Medical Oncology low-, intermediate- and high-risk groups were 88.3%, 84.3%, and 60.3%, respectively (low and intermediate risk vs high risk, P < 0.001). The 5-year biochemical recurrence-free survival rates in the Cancer of the Prostate Strategic Urological Research Endeavor low-, intermediate-, and high-risk groups were 90%, 83.5% and 60.3%, respectively (low and intermediate risk vs high risk, P < 0.001). Low- and intermediate-risk groups according to any of the risk stratification systems did not show significant differences in biochemical recurrence-free survival. Current risk stratification systems do not discriminate between low- and intermediate-risk groups in the Japanese population. A novel, pretreatment risk stratification system including other prognostic factors is necessary for an adequate prostate cancer risk assessment in the Japanese population.

A Novel Multi-Gene Expression Array Allows Highly Sensitive Detection Of Minimal Residual Disease and Predicts Relapse Outcomes In Acute Myeloid Leukemia

IntroductionIt is now clear that traditional response criteria in acute myeloid leukemia based on morphological assessment alone is suboptimal for the prediction of long-term outcome following treatment. While pre-treatment risk stratification based on cytogenetic and molecular correlates of disease biology is highly informative, direct assessment of disease burden after treatment while in traditional complete remission can provide additional prognostic information. Determination of minimal residual disease (MRD) can be performed by a variety of methods; in AML the absence of a unique marker as found in CML and APL has arguably limited the clinical adoption of this higher sensitivity standard. Wilms tumor-1 (WT1) is a commonly over-expressed gene in AML proposed as a standardized MRD assay; unfortunately it is not expressed in 10-20% cases of AML, and is overexpressed to a level necessary for high sensitivity measurements of disease burden in only around 50% of cases.We performed quantitative reverse transcription polymerase chain reaction (qRT-PCR) to determine the magnitude of overexpression of 65 genes using 30 peripheral blood samples from untreated AML patients and 50 healthy normal donor (ND) controls. From this analysis we selected 11 genes with sufficient overexpression for potential use in AML MRD assessment. We tested the predictive and prognostic capacity of this novel multi-gene array to predict hematological relapse using peripheral blood samples from 18 AML patients either prior to, and/or in the surveillance period following, allogeneic stem cell transplantation (SCT). MethodsDe-identified, clinically annotated peripheral blood samples from AML patients who had received allogeneic, non-myeloablative, T-cell depleted SCT from 2004 -2012 collected under IRB-approved protocols at the National Institutes of Health Clinical Center were studied. Expression of 11 genes was assessed using our custom-designed qRT-PCR array, normalized to ABL1 expression and analyzed using the comparative ddCT method After excluding one outlier for each gene, the threshold for positivity was set as the upper limit observed in ND controls. In serial samples, molecular relapse was defined as new gene overexpression seen on two consecutive time-points with the time of relapse defined as first detection of elevation plus 7 days to allow for retesting. ResultsEighteen patients were studied retrospectively. Average age was 41 years (range 17-72) with 10 female and 8 male. Sixteen patients had available pre-transplant peripheral blood with a minimum clinical follow-up of 10 months and 14 patients had at least 6 months of follow-up samples (including a sample in the three months prior to clinical relapse if applicable).In samples from 16 patients taken prior to SCT, WT1 overexpression was detectable in 9 of the 12 patients who relapsed within ten months after SCT and in none of 4 non-relapsing patients (sensitivity: 75%, specificity: 100%, PPV: 100%, NPV: 57%). In comparison, the use of three genes (WT1, CCNA1 and HBG2) from our multi-gene array correctly predicted 11 of these 12 relapsing patients and was also negative in all non-relapsing patients (sensitivity: 92%, specificity: 100%, PPV: 100%, NPV: 80%). For those nine patients judged to be in clinical remission at the time of SCT, the use of WT1 overexpression alone as a marker of MRD predicted only three of the six relapses in the following ten months (sensitivity: 50%, specificity: 100%, PPV: 100%, NPV: 50%) compared to the identification of five of the six relapses (sensitivity: 83%, specificity: 100%, PPV: 100%, NPV: 75%) using our three gene pre-SCT signature.In serial surveillance samples from 14 patients following SCT, 7 of the 11 relapsing patients were detected by WT1 overexpression alone compared to 9 detected using our multi-gene signature (sensitivity 64% vs. 82%), with no false positives detected using either test (specificity 100% and PPV: 100% for both methods). The mean time between detection of molecular relapse and clinical diagnosis using WT1 testing was 24 days (range 0-79 days) compared to 46 days (range 0-179 days) using our multi-gene array. ConclusionAssessment of minimal residual disease for AML using our multi-gene array is highly sensitive and may improve the ability to predict or detect relapse in both the pre and post SCT settings compared to assays of single gene overexpression. This array will now be tested prospectively.▪ Disclosures:No relevant conflicts of interest to declare.