Pretreatment Clinical Data Research Articles

953 Sustained Decline of Noninvasive Fibrosis Index Values in Patients With Chronic Hepatitis C (CHC) With Sustained Virologic Response (SVR) After Receiving Direct-Acting Antiviral Agents (DAAs)

INTRODUCTION: DAAs for CHC are highly effective at achieving SVR. However, there are limited data on outcomes post-SVR. Our aim was to investigate the temporal effect of DAAs on the outcomes of hepatic fibrosis by non-invasive assessment and incidence of HCC post-SVR. METHODS: Retrospective longitudinal study in adults with CHC who received DAAs between 2014 and 2018 and achieved SVR at 12 weeks (SVR12) and/or 24 weeks (SVR24). Data abstracted included demographic data, pre-treatment fibrosis stage, DAA regimen, clinical and laboratory data post-SVR. Fibrosis level was determined post-SVR using APRI and FIB-4. Co-primary study outcomes were FIB-4 values and APRI values post-SVR, and incidence of hepatocellular carcinoma. ANOVA and two-sample t-test statistical analyses were performed using Microsoft Excel. RESULTS: A total of 532 patients were identified retrospectively. Median age at the end of treatment was 60 (55–65) years, 306 (57.5%) were men, baseline median APRI was 0.92, baseline median FIB-4 was 2.67, and 230/532 (43%) were F4 pre-treatment (Table 1). Hispanics had a higher level of pretreatment fibrosis than non-Hispanics (P < 0.01) and higher BMI than whites and Asians (P < 0.001). We observed a significant sustained reduction in APRI scores post-treatment at SVR12/24, and 1 and 2 years post-SVR and FIB-4 scores at 2 years post-SVR within all fibrosis groups and all races (Tables 2 and 3). Hispanics in our cohort had significantly higher fibrosis levels at 1 and 2 years post SVR compared to blacks and Asians (P < 0.01 and P < 0.05, respectively) but not whites. 159 (70%) women and 224 men (73%) achieved a normal ALT less than 25 or 33. 72% of whites, 67 % of Asians, 81% of blacks, and 76% of Hispanics achieved normal ALT level. 22 (4.14%) patients developed hepatocellular carcinoma (HCC) post-treatment; all had F4 fibrosis prior to treatment initiation. CONCLUSION: In a cohort of HCV patients with high prevalence of advanced fibrosis,treatment with DAAs lead to significant improvement in fibrosis indices, across all initial fibrosis stages and races at 1 and 2 years post-SVR. In our cohort, Hispanics had higher baseline fibrosis levels and BMI yet still had a sustained significant improvement 2 years post-SVR though fibrosis levels still remained higher than Asians and blacks. The risk of HCC post-SVR remains in patients with F4 fibrosis.

Prognostic value of pre-treatment peripheral blood markers in pancreatic ductal adenocarcinoma and their association with S100A4 expression in tumor tissue.

The aims of the present study were to clarify the prognostic value of peripheral blood variables in patients with pancreatic ductal adenocarcinoma (PDAC), including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR), and to determine the association between these variables and S100 calcium-binding protein A4 (S100A4) expression in tumor tissue, which is another prognostic factor for PDAC. Patients with PDAC were recruited at the Tianjin Medical University Cancer Institute and Hospital (Tianjin, China) between December 2008 and December 2014. A retrospective analysis was performed based on the recorded pre-treatment hematological parameters and clinical data. The prognostic value of NLR, PLR and LMR was examined. The association between these variables and S100A4 tissue expression was analyzed. Descriptive statistics and χ2 analyses were used in the present study. The median overall survival (OS) time of patients with PDAC was 9 months (range, 1–32 months). Univariate analysis revealed that NLR, LMR, carbohydrate antigen 19-9, surgery, chemotherapy, stage at diagnosis, tumor grade and age significantly affected OS. Although PLR exhibited no significant effects on OS, NLR and LMR were independent prognostic factors according to the multivariate analysis. Unpaired Student's t-test revealed differences between S100A4 expression and NLR, PLR and LMR. The results of the present study indicated that low NLR and high LMR were associated with a favorable prognosis in patients with PDAC. As a simply obtained and widely available index at diagnosis, NLR and LMR may become a novel predictive and classifying marker for PDAC in the clinical setting.

The prognostic factors between different viral etiologies among advanced hepatocellular carcinoma patients receiving sorafenib treatment.

Sorafenib is currently the first-line therapy for advanced hepatocellular carcinoma (aHCC) patients. However, the outcomes and prognostic factors of sorafenib therapy have not been well investigated. We aimed to investigate the pretreatment factors and outcomes among Taiwanese aHCC patients receiving sorafenib treatment. A total of 347 patients with aHCC and well-compensated liver cirrhosis (Child-Pugh A) status receiving sorafenib were consecutively enrolled from March 2013 through December 2016. Pre-treatment clinical data and viral hepatitis markers were collected and analyzed with their outcomes. The primary endpoint of the study was overall survival. The factors associated with overall survival were also investigated. The median overall survival of all the patients was 238 days (range, 9-1504 days) with a 1-year overall survival of 43.2%. Positive hepatitis B surface antigen and absence of portal vein thrombosis (PVT) were independent factors associated with better overall survival. The median duration of sorafenib therapy was 93.0 days (range, 4-1504 days). After stopping sorafenib, the median survival was 93.0 days (range, 1-1254 days). The 1-year survival after stopping sorafenib was 21.2%. In chronic hepatitis B patients, total bilirubin level was the only factor associated with overall survival. Hepatitis C antibody RNA negativity, tumor size, PVT, and white blood cell count were the independent factors associated with survival among those chronic hepatitis C patients. There were different prognostic factors stratified by viral etiologies in aHCC patients receiving sorafenib. Viral eradication increased survival in chronic hepatitis C patients.

Patient-reported symptom-mapping in carpal tunnel syndrome.

To date, no method has been described or utilized to study the distribution of symptoms in carpal tunnel syndrome. We describe a technique of symptom-mapping that yields a population-based "anatomic profile" of carpal tunnel syndrome. Symptoms were mapped on visual questionnaires depicting the volar hand, wrist, and forearm. Thirty-four hands in 26 patients with isolated carpal tunnel syndrome were included in the study. Painful symptoms were clearly centered over the carpal tunnel and were reported much less frequently in the digits. Nonpainful sensory disturbances (e.g., numbness, paresthesias) were found to have a much more peripheral and lateral distribution. Our technique serves to establish a population-based "anatomic profile" of carpal tunnel syndrome, assisting with clinical diagnosis and serving as a reference point for the comparison of pretreatment and posttreatment clinical data. Muscle Nerve 59:321-325, 2019.

Impact of inflammatory marker levels one month after the first-line targeted therapy initiation on progression-free survival prediction in patients with metastatic clear cell renal cell carcinoma.

Progression-free survival of first-line targeted therapy greatly influences the survival of patients with metastatic renal cell carcinoma. We evaluated whether post-treatment inflammatory markers and lactate dehydrogenase levels had impacts on progression-free survival prediction in addition to those of conventional predictors. Two hundred and fifteen patients whose tumors were clear cell type and in whom first-line targeted therapies could be continued for >1 month were evaluated. Pretreatment clinical factors, pathological factors and laboratory data 1 month after targeted therapy initiation-including inflammatory markers (neutrophil count, neutrophil-to-lymphocyte ratio and C-reactive protein) and lactate dehydrogenase-were reviewed. To identify progression-free survival predictors, multivariate analyses were done. The 1-year progression-free survival rate was 47%. Female gender, Karnofsky performance status <80%, time from diagnosis to systemic treatment <12 months, pretreatment C-reactive protein >3.0 mg/dl and post-treatment neutrophil-to-lymphocyte ratio >3.0 were independent predictors for progression-free survival. In contrast, neither C-reactive protein increase nor neutrophil-to-lymphocyte ratio increase after targeted therapy initiation were independent predictors. Pretreatment lactate dehydrogenase, post-treatment lactate dehydrogenase and lactate dehydrogenase decline were not independent predictors. When all patients were stratified by these independent factors into three groups (0 risk vs. 1 or 2 risks vs. 3 or more risks), there were significant differences in progression-free survival rates between the groups (P < 0.0001). Furthermore, there were also significant differences in overall survival rates between the groups (P < 0.0001). Integration of post-treatment neutrophil-to-lymphocyte ratio value with pretreatment factors may lead to the establishment of effective predictive model for disease progression in patients with metastatic clear cell renal cell carcinoma who received first-line targeted therapies.

Nomogram predicting extrahepatic metastasis of hepatocellular carcinoma based on commonly available clinical data.

Background and AimExtrahepatic metastasis (EHM) of hepatocellular carcinoma (HCC) leads to a worse prognosis. We aimed to develop a nomogram based on noninvasive pretreatment clinical data to predict EHM of HCC sooner.MethodsThree cohorts containing 1820, 479, and 988 HCC patients were enrolled from three hospitals in different regions in Taiwan and served as the training and validation cohorts. Pretreatment clinical data were analyzed by Cox regression modeling for independent risk factors of EHM.ResultsPlatelet count ≥ 200 × 103/μL, serum alfa‐fetoprotein ≥ 100 ng/dL, tumor size ≥ 3 cm, tumor number > 1, and macrovascular invasion were independent risk factors for EHM and were used to develop a nomogram. This nomogram had concordance indices of 0.733 (95% confidence interval [CI]: 0.688–0.778) and 0.739 (95% CI: 0.692–0.787) for the prediction of EHM during a 5‐year follow‐up duration in the training and validation cohorts, respectively. A nomogram score > 61 implied a high risk of EHM (hazard ratio [HR] = 3.83; 95% CI: 2.77–5.31, P < 0.001).ConclusionWe have developed a nomogram that could accurately predict EHM of HCC and be readily available for formulating individualized treatment for all individual HCC patients to improve therapeutic efficacy.

Esophageal Cancer in Young Patients: Does Age Play a Role in Treatment Course and Outcomes?

Introduction: Recent studies suggest survival in younger patients with esophageal cancer (EC) is worse, potentially due to differences in disease biology or more advanced stages at diagnosis. The objective of this study is to compare stage at diagnosis, patterns of treatment and outcomes of young patients ≤50 years with EC compared to older patients at a high-volume cancer center. Methods: Query of an IRB approved database of 1039 esophagectomies at our institution revealed 97 patients ≤50 years with esophageal cancer from 1999 to 2017 who underwent an esophagectomy. Demographics, pre-treatment clinical data, treatment modality, and treatment outcomes were analyzed. Statistical analysis was performed with SPSS 24. Results: The median age of the younger cohort is 45.8 (range, 17.6-50 yrs), with a male preponderance (78%). Median follow up is 27 months for the entire cohort. AJCC clinical staging is Stage I 9%, Stage II 37%, Stage III 44%, Stage IV 7% and unknown in 3%, which is comparable to the older cohort (p=0.20). There is a higher incidence of adenocarcinoma in those >50 compared to those ≤50 (86% vs. 76%, p=0.02). There is a higher incidence of patients ≤50 treated with neoadjuvant therapy, but did not reach statistical significance (74% vs. 66%, p=0.072). However, of those receiving neoadjuvant therapy, younger patients received more adjuvant therapy than the older group (34% vs. 10%, p=0.00). Overall, patients ≤50 had a higher chance of disease recurrence, although was not statistically significant (33% vs. 25%, p=0.12). We found no significant difference between patients younger or older than 50 when comparing type of surgery, length of stay in hospital after surgery, postoperative complications, or overall survival. Conclusion: We found no significant difference between patients younger or older than 50 when comparing gender, clinical stage, neoadjuvant therapy administration, surgery type, length of stay in the hospital after surgery, postoperative complications, disease recurrence, or overall survival. Younger patients were more likely to receive adjuvant therapy but this did not improve outcomes, suggesting further investigation of novel systemic strategies postoperatively is needed. Offering earlier endoscopic screening in high risk patients may allow for earlier detection and potentially more effective treatment.

Discrete patterns of cortical thickness in youth with bipolar disorder differentially predict treatment response to quetiapine but not lithium.

The need for treatment response predictive biomarkers is being increasingly recognized in children and adolescents with psychiatric disorders. Structural gray matter abnormalities as a predictor of treatment outcome in pediatric bipolar disorder have not been systematically investigated, especially early in the illness course. With a prospective longitudinal study design, the present study enrolled 52 bipolar adolescents with no history of treatment with mood stabilizers or a therapeutic dose of antipsychotic drugs and31 healthy controls. Patients were randomly assigned to treatment with quetiapine or lithium after pretreatment data collection. A hierarchical cluster analysis was performed using pretreatment cortical thickness data that identified two discrete patient subgroups. Compared to healthy subjects, patients in subgroup 1 (n = 16) showed widespread greater cortical thickness mainly across heteromodal cortex but also involving some regions of unimodal cortex, while those in subgroup 2 (n = 36) showed regional cortical thinning mainly in superior temporal and superior parietal regions. Patients within subgroup 1 showed a significantly higher response rate to quetiapine than those in subgroup 2 (100% vs 53%). No statistically significant difference was found in lithium response rate between the patient subgroups (63% vs 53%). Pretreatment clinical ratings and neuropsychological data did not differ across subgroups. Our findings suggest the existence of distinct and clinically relevant subgroups of pediatric bipolar patients, as defined by pattern of cortical thickness. These groups appear to differentially respond to antipsychotic treatment-notably with greater cortical thickness relative to controls predicting better treatment response.

Real-Life Data on the Use of Ustekinumab for the Treatment of Fistulas in Patients With Crohnʼs Disease

Introduction: Fistulas are a common manifestation of Crohn's disease (CD). Ustekinumab an interleukin 12/23 inhibitor was recently approved for the treatment of patients with moderate to severe CD. Data on its efficacy in fistulizing CD is limited. This study aims to assess its efficacy in CD patients with perianal and rectovaginal fistulas after its FDA approval in September 2016. Methods: We conducted a retrospective chart review of patients with fistulizing CD treated at a large metropolitan IBD center with ustekinumab between September 2016 and June 2017. Data was collected by EMR search. All patients had initial IV followed by subcutaneous ustekinumab dosing. Data collected included demographics, disease characteristics and location, previously failed immunosuppressive meds, concomitant immunosuppressive meds, and lab parameters including CRP, and CBC prior and after initiation of treatment. Pretreatment lab and clinical data was collected at the last visit up to 3 months preceding induction. Post treatment lab and clinical data was collected 1 to 6 months after the infusion aiming closest to the 3 month post-infusion time-point. Fistula response was defined as decrease in fistulous drainage or partial healing of fistulas. Fistula healing was defined as complete closure of fistulas. Clinical response and remission of CD were based on clinical evaluation. Results: We identified 9 CD patients with perianal and/or rectovaginal fistulas who were treated with ustekinumab. All patients had failed prior treatment with anti-TNFs; 5 out of 9 patients had failed treatment with vedolizumab; 5 patients had failed prior treatment with thiopurines; and 2 had failed treatment with methotrexate. During treatment, 3 patients were on concomitant treatment with 6-mercaptopurine and 2 patients with methotrexate. Fistula healing was seen in 1 out of 9 patients (11%), fistula response in 4 out of 9 patients (44%), and no response was seen in 2 out of 9 patients (22%). Fistula evaluation of 2 patients post initiation was pending. Clinical response was seen in 6 out of 9 patients (67%) and none of the patients showed clinical remission. Clinical evaluation was pending in 1 patient.Figure: Patient demographics, disease characteristics and previously failed immunosuppressive treatments. Age in years. Gender: F=Female, M=Male. Disease location as per Montreal Classification (L2: colon, L3: ileocolon, p: perianal). U=unknown.Figure: Concomitant immunosuppressive agents, fistula response or healing and clinical response or remission. CRP and WBCs as evaluated within 3 months prior to infusion and 1-6 months after infusion (for multiple existent lab values we included the ones closest to the infusion for pretreatment and to the 3-month time-point after infusion for the posttreatment). PreRx= Pretreatment and PostRx= Posttreatment. U= unknown.Conclusion: Ustekinumab appears to be effective in patients with fistulizing CD who have failed prior treatment with biologics. Larger studies are needed to examine its use in this patient population with an aggressive disease phenotype.

Systemic Immune-Inflammation Index and Circulating T-Cell Immune Index Predict Outcomes in High-Risk Acral Melanoma Patients Treated with High-Dose Interferon

High-dose interferon alfa-2b (IFN-α-2b) improves the survival of patients with high-risk melanoma. We aimed to identify baseline peripheral blood biomarkers to predict the outcome of acral melanoma patients treated with IFN-α-2b. Pretreatment baseline parameters and clinical data were assessed in 226 patients with acral melanoma. Relapse-free survival (RFS) and overall survival (OS) were assessed using the Kaplan-Meier method, and multivariate Cox regression analyses were applied after adjusting for stage, lactate dehydrogenase (LDH), and ulceration. Univariate analysis showed that neutrophil-to-lymphocyte ratio ≥2.35, platelet-to-lymphocyte ratio ≥129, systemic immune-inflammation index (SII) ≥615 × 109/l, and elevated LDH were significantly associated with poor RFS and OS. The SII is calculated as follows: platelet count × neutrophil count/lymphocyte count. On multivariate analysis, the SII was associated with RFS [hazard ratio (HR)=1.661, 95% confidence interval (CI): 1.066-2.586, P=.025] and OS (HR=2.071, 95% CI: 1.204-3.564, P=.009). Additionally, we developed a novel circulating T-cell immune index (CTII) calculated as follows: cytotoxic T lymphocytes/(CD4+ regulatory T cells × CD8+ regulatory T cells). On univariate analysis, the CTII was associated with OS (HR=1.73, 95% CI: 1.01-2.94, P=.044). The SII and CTII might serve as prognostic indicators in acral melanoma patients treated with IFN-α-2b. The indexes are easily obtainable via routine tests in clinical practice.

MP16-07 USEFULNESS OF INFLAMMATORY MARKER DYNAMICS ONE MONTH AFTER THE FIRST-LINE TARGETED THERAPY INITIATION FOR PFS PREDICTION IN PATIENTS WITH METASTATIC CLEAR CELL RENAL CELL CARCINOMA

MP16-07 USEFULNESS OF INFLAMMATORY MARKER DYNAMICS ONE MONTH AFTER THE FIRST-LINE TARGETED THERAPY INITIATION FOR PFS PREDICTION IN PATIENTS WITH METASTATIC CLEAR CELL RENAL CELL CARCINOMA

Dynamic conformal arc radiosurgery for arteriovenous malformations: Outcome and influence of clinical and dosimetrical data

PurposeTo assess efficacy, toxicity, and their predictive factors for dynamic conformal arc arteriovenous malformations (AVM) stereotactic radiosurgery. MethodData concerning 90 consecutive patients were retrospectively studied. Clinical, radiological, dosimetrical data and quality indexes were computed. ResultsAVM median volume was 1.06cc. Median prescribed dose was 22Gy. Total occlusion was obtained for 69% of patients. Post-radiosurgery annual hemorrhage rate was 2.2%. Predictive factor for total occlusion was delivered dose. Undesirable events occurred for 28% of patients. Predictive factors for adverse events were AVM revealing mode with seizure or headache, age≤28, AVM diameter≥3cm Spetzler–Martin score≥4, V12Gy≥2cc, large target volume and low homogeneity index (p<0.05). Brain parenchymal radiological reactions concerned 23% of patients, and their predictive factors were AVM revelation by seizure, deep localization, AVM diameter≥3cm, Spetzler–Martin score≥4, previous radiosurgery, numerous embolization, target volume, V12Gy and low homogeneity index (p<0.05). ConclusionOcclusion rate and toxicities are comparable to other series. Specific attention must be paid on pre-treatment clinical data, and target volume should be as small as possible, without reducing the delivered dose.

Analysis of the Risk Factors for Severe Oral Mucositis in Head and Neck Cancer after Chemoradiotherapy with S-1.

Radiotherapy (RT) and chemoradiotherapy (CRT) is widely accepted as the standard treatment for head and neck cancer (HNC). Oral mucositis (OM) often develops as an adverse reaction in HNC patients that receive RT or CRT involving S-1. However, little is known about the risk factors for OM in HNC patients. We retrospectively evaluated patients' pre-treatment clinical data in order to identify the risk factors for severe OM in HNC patients that are treated with RT or CRT involving S-1. We analyzed the cases of 129 patients who received RT or CRT involving S-1 for HNC. The endpoint of the survey was the occurrence of severe OM (≥grade 2). Risk factors that were significantly related to severe OM were identified using logistic regression analysis. The patients' mean age was 69.3±10.1 years, and 118 (92%) of the patients were male. The primary tumor was located in the oropharynx in 21.7% of cases. Severe OM occurred in 85.0% of cases. In the univariate analysis, the following variables were found to be associated with severe OM: age, the type of radiotherapy, disease stage, and chemotherapy. In the multivariate analysis, the location of the primary tumor and chemotherapy were identified as significant risk factors that contributed independently to the risk of severe OM (p<0.05). Our analysis suggests that cancer of the oropharynx and CRT are important risk factors for severe OM in HNC patients that undergo RT or CRT involving S-1.

Esophageal Cancer in Young Patients: Is Aggressive Treatment Associated With Better Outcomes?

54 Background: Recent studies suggest that survival in young patients with esophageal cancer (EC) is worse than their older counterpart, secondary theoretically to more aggressive disease and late stage at diagnosis. The aim of this study is to compare stage at diagnosis, patterns of treatment and outcomes of young patients with EC at Moffitt Cancer Center (MCC). Methods: Patients with EC treated surgically between 1996 and 2014 at MCC were recorded at an IRB approved database. We divided the patients into two cohorts, those younger or older than 50 years of age. Demographics, pre-treatment clinical data, therapeutic courses and treatment outcomes were analyzed. We compared clinical variables and defined p < 0.05 as statistically significant. Overall survival was examined using the Kaplan-Meier method. Results: Of the 816 patients treated surgically for EC 86 (10.5%) were < 50 years old. The majority of patients were male 622(85.2%) vs. 67(77.9%) in the younger group (p =.084). Of the 816 patients, 569 ha...

Pretreatment Serum Folate Levels and Toxicity/Efficacy in Colorectal Cancer Patients Treated With 5-Fluorouracil and Folinic Acid

Background5-Fluorouracil (5-FU) chemotherapy is associated with severe and unpredictable toxicity in a significant proportion of patients. 5,10-Methylenetetrahydrofolate and 5-fluorodeoxyuridine monophosphate bind to thymidylate synthase and together inhibit its function, resulting in cytotoxicity. We hypothesized that susceptibility to 5-FU toxicity might be related to individual differences in the serum components of folate metabolism affecting intracellular 5,10-methylenetetrahydrofolate levels. Patients and MethodsA prospective cohort of chemotherapy-naive colorectal cancer patients scheduled to receive intravenous 5-FU and folinic acid for 5 consecutive days every 4 weeks in both adjuvant and palliative settings was studied. Pretreatment clinical and laboratory data were collected. Biochemical data associated with folate metabolism were also collected. The primary endpoint was the occurrence of grade ≥ 3 toxicity and/or toxicity mandating dose delay or reduction. ResultsFor the 78 eligible patients studied, multivariable analyses identified only a greater pretreatment serum folate level as an independent predictor of grade ≥ 3 toxicity and/or mandating schedule modification (P = .016). Comparing the patient cohorts among the folate quartile groups revealed increasing toxicity trends in the highest quartile with an odds ratio of 2.58 (P = .19) compared with the combined lower quartiles, and superior relapse-free and overall survival for patients treated in the adjuvant setting. Log-rank analysis showed a significant association between higher folate levels and relapse-free and overall survival. ConclusionThe pretreatment serum folate level did not conclusively influence 5-FU toxicity and antitumor efficacy. However, high folate levels showed a trend toward a greater incidence of severe toxicities but also lower rates of disease recurrence and mortality. These results provide promising hypothesis-generating data warranting further investigation. The predictive value of pretreatment folate status should be a priority for study in cancer patients receiving 5-FU–based chemotherapy and should be considered a potentially confounding factor in clinical trials and a modifiable parameter in treatment.

Esophageal cancer in young patients: Is aggressive treatment associated with better outcomes?

54 Background: Recent studies suggest that survival in young patients with esophageal cancer (EC) is worse than their older counterpart, secondary theoretically to more aggressive disease and late stage at diagnosis. The aim of this study is to compare stage at diagnosis, patterns of treatment and outcomes of young patients with EC at Moffitt Cancer Center (MCC). Methods: Patients with EC treated surgically between 1996 and 2014 at MCC were recorded at an IRB approved database. We divided the patients into two cohorts, those younger or older than 50 years of age. Demographics, pre-treatment clinical data, therapeutic courses and treatment outcomes were analyzed. We compared clinical variables and defined p &lt; 0.05 as statistically significant. Overall survival was examined using the Kaplan-Meier method. Results: Of the 816 patients treated surgically for EC 86 (10.5%) were &lt; 50 years old. The majority of patients were male 622(85.2%) vs. 67(77.9%) in the younger group (p =.084). Of the 816 patients, 569 had pre-treatment staging information available. Pre-treatment clinical staging for the older and younger cohorts was, Stage0/TIS = 13(2.2%) vs. 1(1.4%); Stage I = 90(15.3%) vs. 6(8.3%); Stage IIA = 119(20.3%) vs. 16(22.2%); Stage IIB = 88(15.0%) vs. 8(11.1%); Stage III = 269(46%) vs. 40(55%); Stage IV = 8(1.4%) vs. 1(1.3%)(p =.44). Younger patients were more likely to receive neoadjuvant therapy (75.6% vs.62.1%)(p =.013), and also neoadjuvant combined with adjuvant therapy, 24(41.4%) compared to 48(12.1%) in the older cohort (p =.001). Pathological complete response (pCR) rate was higher in older patients (43.2% vs 32%)(p =.204); Median survival was higher in younger cohort 64.3 vs. 56.4 months. Neither of these were statically significant (p =.516). Conclusions: This retrospective study with several variables only included surgical patients. In our experience, younger age was not associated with late stage presentation. Younger patients were more likely to be treated with neoadjuvant therapy, and despite similar pathologic response rates they were more likely to receive adjuvant therapy. Although younger patients received more aggressive treatment, their overall survival did not differ from their older counterparts.

Genomic predictors of biochemical failure following radical prostatectomy.

114 Background: Although clinical correlates can help predict biochemical failure (BF), genomic correlates have yet to be identified. We hypothesized there would exist genomic profiles in patients who experience BF after radical prostatectomy (RP), for whom aggressive regional therapy may be more appropriate. Methods: Genes of interest were identified using the 25 most commonly mutated genes from the COSMIC dataset. The Cancer Genome Atlas (TCGA) was used to study normalized microarray gene expression data for patients who underwent RP for treatment of Gleason 7-10, T1/T2 N0 prostate adenocarcinoma. BF was considered PSA &gt; 0.1 following prostatectomy. Clinical data of interest included age, pre-treatment PSA, Gleason score, pathologic T stage, and country of origin. A multi-level hierarchical logistic regression model clustered with random effects by pathologic T stage and country of origin was built to identify predictors of BF. Variances were used to estimate how genomic differences explained differences in BF. Results: We identified 296 patients with T1/T2 N0 prostate adenocarcinoma who underwent RP. Median age was 60 with a median follow up of 2.3 years. 59% (n = 177) had Gleason 7 disease and 54% (n = 154) had T1 disease. 40.8% (n = 121) of patients had BF following RP. After adjusting for clinical covariates, 4 genes were associated with differences in BF. Specifically, increased RNA expression of E2F3 (OR 1.11 p &lt; .001), CTNNB1 (OR 1.49, p = .002), and AR (OR 1.21, p &lt; .001) were seen in patients who experienced BF. Expression of TP53 (OR 0.75, p &lt; .001) and Gleason 7 disease (OR 0.62 vs. Gleason 8-10, p &lt; .001) were associated with decreased likelihood of BF. Clustering by pathologic T stage accounted for 10% of variance in BF indicating that the 4 genes augment clinical patient characteristics. Conclusions: Genomic data augments pre-treatment clinical data in the stratification of patients undergoing RP. RNA expression of E2F3, CTNNB1, AR and TP53 is associated with differences in BF following RP. Clinically, these genes could aid in identifying patients who may benefit from more aggressive therapy. Further studies of the relationship between these genes and the development of prostate cancer could aid in future targeted therapies.

Complex Karyotype in Mantle Cell Lymphoma (MCL) Is Associated with Inferior Progression-Free Survival in Patients (pts) Receiving R-Hypercvad Followed By Autologous Stem Cell Transplant

Introduction: While cytogenetic assessments are frequently utilized in many hematologic malignancies as prognostic markers, their role in MCL is less well defined. Prior studies have identified a complex karyotype (≥3 chromosomal abnormalities) in 40 - 59.2 % of patients (pts) with MCL, and it has been associated with inferior progression-free survival (PFS) in those series (Cohen et al, 2015; Sarkozy et al, 2014). Our group recently published outcomes for MCL pts at our institution, including 35 pts who received R-HyperCVAD followed by autologous stem cell transplantation (ASCT) who had an overall survival (OS) at 5-years of 74% (Nastoupil et al, 2014). We conducted an analysis of the impact of pretreatment cytogenetics on outcomes for MCL.Methods: We included all pts diagnosed with MCL at Winship Cancer Institute of Emory University between 2002 and 2014 who had available pretreatment conventional cytogenetic and clinical data. Baseline demographic, clinical, laboratory, and therapeutic variables of interest were assessed. Univariate Cox proportional hazards models were fit for each covariate, and hazard ratios are reported. Overall survival (OS) was defined as time to death or last follow-up from diagnosis, and PFS was defined as time to progression, death, or last follow-up from diagnosis. These curves were estimated via the Kaplan-Meier method, and the groups were compared using log-rank tests. We performed a similar analysis for the subset of pts initially treated with HyperCVAD and ASCT. Statistical significance was defined as α=0.05.Results: Among 184 MCL pts, 52 had pretreatment cytogenetics data available. The median age at diagnosis was 64 years (range: 32-81), 36 (69%) were male, and 37 (86%) had stage IV disease. At diagnosis, 36 pts (97%) had ECOG performance status of 0 or 1, 16 (34%) had B-symptoms, 43 (86%) had bone marrow involvement, 8 (16%) had gastrointestinal tract involvement, and 29 (71%) had splenomegaly. Initial induction therapies included R-HyperCVAD (n=27), R-CHOP (n=10), R-bendamustine (n=6), and other/unknown (n=9). Thirty pts (58%) underwent ASCT in first complete or partial remission. Five pts (10%) met criteria for a complex karyotype, 11 (21%) had 1 or 2 detectable chromosomal abnormalities, and 36 (69%) pts had a normal karyotype. Cytogenetics were assessed on nodal samples (n=7) or bone marrow/peripheral blood (n=45). Among all assessed covariates, only elevated WBC count was associated with cytogenetic abnormalities (p=0.04). Overall, there was no significant association of PFS or OS with the presence of a complex karyotype or an abnormal karyotype with < 3 abnormalities when compared to a normal karyotype. Among all assessed variables, only splenomegaly was associated with worsened PFS (p=0.02). We conducted an exploratory analysis of the 24 pts who received R-HyperCVAD followed by ASCT, of which 2 had a complex karyotype. In that subset, median PFS for pts with a complex karyotype was 35.3 months, compared to 77.9 months for those with a non-complex abnormal karyotype or a normal karyotype.Conclusion: Contrary to prior reports, a smaller percentage of pts had complex karyotype (10%) in this cohort, and pretreatment cytogenetics did not impact PFS or OS among the entire heterogeneously treated sample. However, there appears to be inferior PFS for pts with a complex karyotype in the subset who received R-HyperCVAD followed by ASCT, and a larger, multi-center series, may illuminate the impact of a complex karyotype on this subset of aggressively treated patients. DisclosuresNastoupil:AbbVie: Research Funding; Genentech: Honoraria; Celgene: Honoraria; TG Therapeutics: Research Funding; Janssen: Research Funding. Flowers:Infinity Pharmaceuticals: Research Funding; Spectrum: Research Funding; Acerta: Research Funding; Janssen: Research Funding; Infinity Pharmaceuticals: Research Funding; Onyx Pharmaceuticals: Research Funding; Seattle Genetics: Consultancy; Gilead Sciences: Research Funding; Millennium/Takeda: Research Funding; Pharmacyclics: Research Funding; Janssen: Research Funding; Gilead Sciences: Research Funding; Acerta: Research Funding; AbbVie: Research Funding; Pharmacyclics: Research Funding; Onyx Pharmaceuticals: Research Funding; Millennium/Takeda: Research Funding; OptumRx: Consultancy; AbbVie: Research Funding; Seattle Genetics: Consultancy; Genentech: Research Funding; OptumRx: Consultancy; Genentech: Research Funding; Celegene: Other: Unpaid consultant, Research Funding; Celegene: Other: Unpaid consultant, Research Funding; Spectrum: Research Funding. Cohen:Celgene, Pharmacyclics, Millennium, Seattle Genetics: Consultancy; BMS, Janssen: Research Funding.

Hypopituitarism patterns among adult males with prolactinomas

Base on pretreatment clinical data of 107 patients, we retrospectively characterized hypopituitarism adult men harboring prolactionomas. The incidence of growth hormone deficiency and hypogonadism is the most common pattern. As to adult males harboring macroprolactinomas (>1 cm), maximal adenoma diameter and higher prolactin level are no more the primary factor causing hypopituitarism, but affecting the degree of hormone insufficiency. (Chin J Endocrinol Metab, 2015, 31: 877-879) Key words: Hypopituitarism; Prolatinoma; Adult males; Pituitary

Association of IL28B Polymorphisms With the Response to Peginterferon Plus Ribavirin Combined Therapy in Polish Patients Infected With HCV Genotype 1 and 4

BackgroundThree single nucleotide polymorphisms (SNPs) near interleukin-28B (IL-28B) gene were shown to be highly associated with treatment response (SVR) in patients with chronic hepatitis C virus (HCV) infection. There is limited data about the role of single and combined IL-28B polymorphisms in HCV-infected Polish population.ObjectivesThis study's aim was to determine predictability of three IL-28B gene polymorphisms and other known prognostic factors on the treatment response in HCV genotype 1 and 4 infected Polish patients. The effect of IL-28B polymorphisms on therapy was also compared with other known prognostic factors.Patients and MethodsWe genotyped IL-28B polymorphisms (rs12979860, rs12980275 and rs8099917) by polymerase chain reaction-based restriction fragment length polymorphism assay in a group of 293 patients from which a selected cohort of 174 treatment-naiev patients underwent treatment.ResultsWe showed that rs12979860 CC [odds ratio (OR) = 4.6, P < 0.001], rs12980275 AA (OR = 2.9, P = 0.002) and rs8099917 TT (OR = 2.2, P = 0.016) genotypes were associated with successful treatment compared to the rs12979860 CT-TT, rs12980275 AG-GG and rs8099917 TG-GG, respectively. Patients bearing of IL-28B profile including the three favourable genotypes do not have much chance of a recovery (OR = 3.4, P = 0.002). Except for IL-28B polymorphisms, there was no association of SVR with any other pretreatment clinical data in analyzed group. The correlation of SNPs with other host and viral factors revealed association of favorable genotypes of IL-28B markers with high levels of alanine aminotransferase and baseline HCV viral load.ConclusionsIL-28B polymorphisms were the strongest pretreatment predictors of response to pegylated interferon and ribavirin in Polish patients chronically infected with HCV genotype 1 and 4. This study confirm the strongest impact of IL-28B rs12979860 on SVR, nevertheless rs12980275 AA seems to be more important than rs8099917 TT in predicting positive treatment response.