Independent Predictor Of Worse Overall Survival Research Articles

Utility of radiation after neoadjuvant chemotherapy for surgically resectable esophageal cancer.

172 Background: Neoadjuvant chemotherapy (NAC) is the gold standard approach for locally advanced esophageal cancer (EC), however the addition of radiation remains largely controversial. We sought to investigate the role of neoadjuvant radiation in resectable EC by comparing outcomes of patients who underwent neoadjuvant chemotherapy with (NACR) or without radiation (NAC) using a large nationwide cohort. Methods: National Cancer Data Base (NCDB) was queried for patients with non-metastatic EC between 2010 and 2014. Kaplan-Meier, log-rank and Cox multivariable regression analysis were performed to calculate overall survival (OS). Logistic regression was used to identify factors associated with 90-day mortality and complete pathological response (pCR). Results: A total of 12,546 EC patients who underwent neoadjuvant therapy were included: the majority were males (84%), Caucasians (90.3%), and had adenocarcinoma (81.1%), cT3 (60.6%) and cN1 (49.1%). 11,269 (89.8%) patients had NACR, whereas 969 (7.7%), NAC alone. pCR rate was 14.1% (19.2%, NACR vs. 6.3%, NAC, p < 0.001). Neoadjuvant radiation was an independent predictor for improved pCR [HR 0.305, 95% CI 0.205-0.454, p < 0.001], however OS was similar in patients undergoing NAC with or without radiation (35.9 vs. 37.6 months, respectively, p = 0.393). This persisted regardless of tumor staging. There was a trend towards worse 90-day mortality after radiation (8.2%, NACR vs. 7.7%, NAC; HR 1.410, 95% CI 0.975-2.038, p = 0.068). In Cox regression, controlling for patient and disease-related factors, neoadjuvant radiation was an independent predictor of worse OS (HR 1.322, 965% CI 1.177-1.485, p < 0.001). Conclusions: This is the largest study comparing NACR versus NAC in resected EC. The addition of radiation to neoadjuvant chemotherapy is associated with improved pathological response rates, however it had deleterious effects in long-term and possibly, short-term survival. Our findings suggest that NAC without radiation may be the optimal neoadjuvant therapy in resectable EC, however further evidence with randomized clinical trials is warranted.

Positive cystic duct margin at index cholecystectomy in incidental gallbladder cancer is an important negative prognosticator

BackgroundPrognostic factors following index-cholecystectomy in patients with incidental gallbladder cancer (IGBC) are poorly understood. The aim of this study was to assess the value of the initial cystic duct margin status as a prognosticator factor and to aid in clinical decision making to move forward with curative intent oncologic extended resection (OER). MethodsThis retrospective study included patients with IGBC who underwent subsequent OER with curative intent at 2 centers (USA and Chile) between 1999 and 2016., Patients with and without evidence of residual cancer (RC) at OER were included. Pathologic features were examined, and predictors of overall survival (OS) were analyzed. ResultsThe study included 179 patients. Thirty-three patients (17%) had a positive cystic duct margin at the index cholecystectomy. Forty-two patients (23%) underwent resection of the common bile duct. OS was significantly worse in the patients with a positive cystic duct margin at index cholecystectomy (OS rates at 5 years, 34% vs 57%; p = 0.032). Following multivariate analysis, only a positive cystic duct margin at index cholecystectomy was predictive of worse OS in patients with no evidence of residual cancer (RC) at OER (hazard ratio, 1.7 95%CI 1.04–2.78; p = 0.034). ConclusionsA positive cystic duct margin at index-cholecystectomy is a strong independent predictor of worse OS even if no further cancer is found at OER. In patients with positive cystic duct margin and no RC at OER common bile duct resection leads to improved outcomes.

Adjuvant therapy in stage III endometrial cancer confined to the pelvis

ObjectiveTo review outcomes of patients with stage III endometrial cancer confined to the pelvis treated with adjuvant pelvic radiotherapy (RT) or sequential chemoradiotherapy (CRT). MethodsBetween 1990 and 2012, 144 patients diagnosed with stage IIIA, B or C1 endometrial cancer were treated in our institution. All were treated with total hysterectomy, bilateral salpingo-oophorectomy ± lymph node dissection. Post-operatively, 67 patients received adjuvant RT alone, 37 CRT, 21 chemotherapy alone and 19 had no adjuvant therapy. This analysis focuses on the 104 patients treated with RT or CRT. ResultsThe median follow-up was 61 months. Forty-six patients (44%) were stage IIIA, 6 (6%) were stage IIIB and 52 (50%) stage IIIC1. The 5-year overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS) for patients treated by RT alone vs. CRT were, respectively, 67% vs. 61% (p = 0.55); 67% vs. 51% (p = 0.35); and 76% vs. 65% (p = 0.21). Grade 3 disease was an independent predictor for worse OS (HR = 6.01, p = 0.001), DFS (HR = 3.16, p = 0.03), and DSS (HR = 3.77, p = 0.02). In patients with grade 3 disease (n = 49), the 5-year OS was superior for the CRT (42% vs. 56%, p = 0.007). ConclusionsIn patients with stage III endometrial cancer confined to the pelvis, the addition of adjuvant chemotherapy with RT significantly improved OS in grade 3 disease. Grade 3 histology is a strong predictor for poor outcome. Further randomized studies aiming specifically at stage III disease are warranted.

Preoperative Low Lymphocyte-to-Monocyte Ratio Predicts Poor Clinical Outcomes for Patients with Urothelial Carcinoma of the Upper Urinary Tract.

Urothelial carcinoma of the upper urinary tract (UUTUC) is a rare genitourinary tumor. Pre-operative lymphocyte-to-monocyte ratio (LMR) is associated with worse outcome in several malignancies. The aim of this study was to determine the prognostic value of pre-operative LMR in UUTUC. A historical cohort of 100 UUTUC patients was recruited from January 1990 to June 2011. The counts of peripheral lymphocyte and monocyte were retrieved, and the LMR was calculated by dividing lymphocyte count by monocyte count. Receiver operating characteristic curve (ROC) analysis, Log-rank test and Cox proportional hazards regression models were used for univariate and multivariate analyses to evaluate theassociations of LMR with overall survival (OS) and disease-free survival (DFS). Univariate analysis revealed that low level of LMR (? 3.0) was significantly associated with worse OS (P = .024) but not DFS (P = .993). Multivariate Cox proportional hazard analysis showed that low level of LMR was a significantly independent predictor for worse OS (hazard ratio = 0.366, 95% confident interval: 0.180-0.744). Based on the results of multivariate analysis, the rates of OS at 5 years developed by the prognostic model were asfollows: low risk, 88.0%, intermediate risk, 44.0%, and high risk, 13.0%, respectively. The pre-operative LMR serves an independent prognostic biomarker in UUTUC. The prognostic model based on the LMR and pathologic factors can be available in selection of high risk patients for further aggressive therapy.

Dosimetric Predictors of Symptomatic Cardiac Events Among Patients Receiving Conventional-Dose Radiation Therapy for Inoperable Non-Small Cell Lung Cancer

There is increasing recognition that radiation therapy (RT) can cause cardiac toxicity in patients with inoperable non-small cell lung cancer (NSCLC). Recent studies suggest an association between heart doses and cardiac toxicity in the setting of dose escalation (median prescribed doses 70-74 Gy). We herein assess for this same association among patients treated with conventional RT doses (∼60 Gy). Records of 140 patients with inoperable NSCLC treated with definitive and concurrent chemo-RT from 2007-2015 were retrospectively reviewed. Baseline cardiac status (per baseline coronary artery disease [CAD] or World Health Organization / International Society of Hypertension score), and post-RT symptomatic cardiac events (acute coronary syndrome [ACS], new-onset arrhythmia, pericardial effusion, pericarditis, and congestive heart failure [CHF] not associated with other events) were noted. Dosimetric parameters were extracted for the whole heart (WH), left ventricle (LV), right ventricle (RV), left atrium (LA), right atrium (RA), and left anterior descending artery (LAD). Time to first symptomatic cardiac event and time to distinct event types were estimated with the cumulative incidence method, compared with Gray’s test, and modeled with Fine-Gray. Cox models were developed for overall survival (OS). Median follow-up was 47 months. Median prescribed RT dose was 61 Gy (IQR, 60-66 Gy). 29% (n = 40/140) of patients developed 47 symptomatic cardiac events (8 ACS, 22 arrhythmia [21 supraventricular], 4 pericardial effusion, 1 constrictive pericarditis, 12 CHF) at a median of 15 months to first event post-RT. On multivariate analysis, higher WH doses (e.g., mean WH dose [p < 0.001]) and baseline cardiac status were associated with an increased risk of symptomatic cardiac events. 3-year cumulative incidence of symptomatic cardiac events was 46% vs 17% for mean WH dose ≥ 20 Gy vs < 20 Gy (p < 0.001). On analysis of distinct event types, higher mean doses to the WH (p < 0.001), LV (p = 0.001), RV (p < 0.001), and LAD (p < 0.001) were associated with an increased risk of pooled ACS or CHF events after controlling for baseline CAD, while higher mean doses to the WH (p = 0.15), LA (p = 0.29) and RA (p = 0.51) were not associated with supraventricular arrhythmic events. Both symptomatic cardiac events (p < 0.001) and disease progression (p < 0.001), when treated as time-dependent covariates, were independent predictors of worse OS. This study suggests that cardiac irradiation increases the risk of symptomatic cardiac events, particularly ACS and CHF, among inoperable NSCLC patients receiving conventional RT doses. Additional study is warranted to better establish dosimetric relationships for cardiac toxicity. Based on this analysis and others, a reasonable constraint might be to keep mean WH dose < 20 Gy.

SMAD4 gene mutation predicts poor prognosis in patients undergoing resection for colorectal liver metastases

Introduction: Dorsophilia protein, mothers against decapentaplegic homolog 4 (SMAD4) is a key mediator in the transforming growth factor (TGF)-β signaling pathway and SMAD4 gene mutations are thought to play a critical role of in colorectal cancer (CRC) progression. However, little is known about its influence on survival in patients undergoing resection for CLM. Methods: Between 2005 and 2015, all patients with known SMAD4 mutation status who underwent resection of CLM were identified. Patients with SMAD4 mutation were compared to those with SMAD4 wild type. Next, the prognostic value of SMAD4 mutation was validated in a separate cohort of patients with synchronous stage IV CRC who underwent systemic therapy alone. Results: Of 278 patients, 37 (13%) were SMAD4 mutant while 241 (87%) were wild type. Overall survival (OS) after hepatic resection was worse in SMAD4-mutant patients compared to SMAD4 wild type (OS rate at 3 years, 62% vs. 82%; P< 0.0001). Independent predictors for worse OS were poor differentiation (hazard ratio [HR] 2.586; P=0.007), multiple tumors (HR 1.970; P=0.01), diameter greater than 3 cm (HR 1.752; P=0.017), R1 margin status (HR 2.452; P=0.014), RAS mutation (HR 2.044; P=0.002), and SMAD4 mutation (HR 2.773; P< 0.0001). Among 237 patients in the validation cohort, SMAD4-mutations were significantly associated with worse 3-year OS rate (22% vs. 38%; P=0.012) and was an independent predictor for worse OS (HR, 1.647; P=0.032). Conclusion: SMAD4 mutation is independently associated with worse outcomes in patients undergoing resection of CLM.

Incidence and Outcomes of Delayed Targeted Therapy After Cytoreductive Nephrectomy for Metastatic Renal-Cell Carcinoma: A Nationwide Cancer Registry Study.

The optimal timing of targeted therapy (TT) initiation for metastatic renal-cell carcinoma (mRCC) is not clear. We used a nationwide cancer registry to determine clinical and social factors associated with delayed TT and to evaluate the association of a delayed approach with overall survival (OS). We performed a retrospective observational study utilizing the National Cancer Data Base from 2006 to 2012 for patients diagnosed with mRCC (clear-cell histology) treated with cytoreductive nephrectomy and TT. Time to initiation of TT was defined as early (within 2 months), moderately delayed (2-4 months), delayed (4-6 months), and late (> 6 months). Of the 2716 patients included in the analysis, the median (interquartile range) time from diagnosis to initiation of TT was 2.1 (1.3-3.23) months. A total of 1255 patients (46.2%) had early TT, 1072 patients (39.5%) had moderately delayed TT, 284 patients (10.5%) had delayed TT, and 105 patients (3.9%) had late TT. Delay in TT initiation was not independently associated with OS in multivariable analysis. The time interval from diagnosis to TT initiation was not correlated with time from initiation of TT to death (r= 0.04, P= .08). We found that delayed initiation of TT was not an independent predictor of worse OS. Although this study is subject to limitations of observation study design and selection bias, the results are consistent with the notion that in carefully selected patients, outcomes might not be compromised with initial observation.

Lymph node yield as a predictor of overall survival following inguinal lymphadenectomy for penile cancer

ObjectiveTo determine whether a specific lymph node yield (LNY) affects overall survival (OS) in patients with penile cancer. Materials and MethodsUsing the National Cancer Database, we identified 364 men diagnosed with pSCC who underwent ILND between 2004 and 2013. Men diagnosed on autopsy or at the time of death, patients with preoperative chemotherapy or radiotherapy, M+ and N3 disease, or with less than 3-month of follow-up were excluded. Kaplan-Meier analysis was used to compare Overall Survival (OS). A multivariable Cox regression model was developed to assess predictors of OS. ResultsThe median number of LN retrieved was 16 (IQR: 9-23). There was no significant difference in race, stage, grade for men with LNY ≤15 vs. >15. However, men with LNY ≤15 were significantly older than those with LNY >15 (65 vs. 59 years, p<0.001). On multivariable analysis, radical surgery, age, N+ disease, and LNY ≤15 were independent predictors of worse OS. Patients with LNY ≤15 showed significantly worse 5-year OS versus those with LNY >15 (49% vs. 67%, p=0.008). Nodal density (ND) ≥12.5% was also associated with decreased 5-year OS versus ND <12.5% (31% vs. 70%, p<0.0001). ConclusionsLNY following ILND for pSCC appears to be an independent predictor of OS. A total LNY of >15 following ILND may have a beneficial impact on OS and serve as the threshold for defining an adequate ILND.

Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Penile Squamous Cell Carcinoma Patients Undergoing Inguinal Lymph Node Dissection

BackgroundFurther biomarkers are warranted to improve prognostic stratification of penile squamous cell carcinoma (PSCC) patients undergoing inguinal lymph node dissection (ILND). ObjectiveTo assess the prognostic value of pretreatment neutrophil-to-lymphocyte ratio (NLR) in PSCC patients undergoing ILND and to investigate its role in predicting pathologic node-positive (pN+) disease. Design, setting, and participantsIn total, 84 consecutive patients undergoing ILND for PSCC at our institution between 1994 and 2014 were identified. Sixty-eight patients with a complete blood count and differential prior to surgery were included. Median follow-up was 35.5 mo. Outcomes measurements and statistical analysisCut-off point analysis of NLR was performed using the Contal and O’Quigley method. Estimates of overall survival (OS), cancer-specific survival, and recurrence-free survival stratified by NLR were provided by the Kaplan-Meier method. Cox regression models were performed to determine predictors of survival and recurrence. Logistic regression models were used to identify factors associated with pathologic node-positivity. Results and limitationsThe cut-off point value was determined to be 3. Median OS was significantly shorter for patients with NLR ≥3 than those with NLR <3 (30 vs 158 mo, p<0.001). NLR ≥3 was an independent predictor of worse OS (hazard ratio=2.48; 95% confidence interval [CI]: 1.02–6.06, p=0.046). On univariable analysis, NLR ≥3 was associated with an increased risk of pN+ disease (odds ratio [OR]=3.75; 95% CI: 1.30–10.81, p=0.014). However, on multivariable analysis adjusted for primary tumor grade, lymphovascular invasion, clinical N stage, and neoadjuvant treatment receipt, the association between NLR and pN+ disease was no longer significant (OR=3.66; 95% CI: 0.82–16.42, p=0.091). The retrospective design and limited size of the study are acknowledged limitations. ConclusionsPretreatment NLR is an independent predictor of OS in PSCC patients undergoing ILND and highlights the association between systemic inflammation and survival. Our data suggests that a simple biomarker of inflammation can serve as a prognosticator in PSCC. Patient summaryPenile cancer is a rare malignancy in North America and Europe. Therefore, there is a lack of prognostic parameters to help predict oncologic and survival outcomes. In this report, patients with an elevated neutrophil-to-lymphocyte ratio had an increased risk of mortality.

Prognostic value of pretreatment plasma D-dimer levels in patients with diffuse large B cell lymphoma (DLBCL)

BackgroundWe assessed the prognostic significance of D-dimer in patients of diffuse large B cell lymphoma (DLBCL). MethodsWe performed a retrospective study including 254 patients who were newly diagnosed DLBCL. X-tile was used to generate a cutoff value for D-dimer. Both univariate screen by Cox proportional hazard model and multivariable analysis by Cox regression model were used to assess the impact of pretreatment D-dimer levels on the overall survival (OS). ResultAccording to X-tile, the optimal cut-off value of D-dimer for prediction of survival was set as 1.6 μg/mL, and a D-dimer level ≥ 1.6 μg/mL was significantly associated with poor overall survival (OS) (OS: 31.7 vs. 79.1%, P < 0.001). In multivariable analysis, it was found that a higher D-dimer level was an independent predictor for worse OS (Hazard ratio (HR): 3.594 95% Confidence interval (CI): 2.296–5.267, P < 0.001). In subgroup analysis of International Prognostic Index (IPI), survival of low-risk and intermediate-risk group with a D-dimer level ≥ 1.6 μg/mL were both similar to that of the high-risk group (OS: 31.6 vs. 36.5%, P = 0.957; OS: 38.0 vs. 36.5%, P = 0.758). In addition, among patients treated with surgery, those with higher D-dimer had substantially worse survival than that with lower D-dimer (OS: 27.0 vs. 84.5%, P < 0.001). ConclusionPretreatment D-dimer is a simple but effective predictor of survival among patients with DLBCL.

SMAD4 gene mutation predicts poor prognosis in patients undergoing resection for colorectal liver metastases

IntroductionDorsophilia protein, mothers against decapentaplegic homolog 4 (SMAD4) is a key mediator in the transforming growth factor (TGF)-β signaling pathway and SMAD4 gene mutations are thought to play a critical role in colorectal cancer (CRC) progression. However, little is known about its influence on survival in patients undergoing resection for colorectal liver metastases (CLM). MethodsBetween 2005 and 2015, all patients with known SMAD4 mutation status who underwent resection of CLM were identified. Patients with SMAD4 mutation were compared to those with SMAD4 wild type. Next, the prognostic value of SMAD4 mutation was validated in a separate cohort of patients with synchronous stage IV CRC who underwent systemic therapy alone. ResultsOf 278 patients, 37 (13%) were SMAD4 mutant while 241 (87%) were wild type. Overall survival (OS) after hepatic resection was worse in SMAD4-mutant patients compared to SMAD4 wild type (OS rate at 3 years, 62% vs. 82%; P < 0.0001). Independent predictors for worse OS were poor differentiation (hazard ratio [HR] 2.586; P = 0.007), multiple tumors (HR 1.970; P = 0.01), diameter greater than 3 cm (HR 1.752; P = 0.017), R1 margin status (HR 2.452; P = 0.014), RAS mutation (HR 2.044; P = 0.002), and SMAD4 mutation (HR 2.773; P < 0.0001). Among 237 patients in the validation cohort, SMAD4-mutations were significantly associated with worse 3-year OS rate (22% vs. 38%; P = 0.012) and was an independent predictor for worse OS (HR, 1.647; P = 0.032). ConclusionSMAD4 mutation is independently associated with worse outcomes among patients undergoing resection of CLM.

The impact of adjuvant vaginal brachytherapy in women with Stage II uterine endometrioid carcinoma: Results of a National Cancer Database analysis

PurposeTo report survival outcomes in women with Stage II uterine endometrioid carcinoma who received adjuvant radiation therapy (RT) without chemotherapy using the National Cancer Database. Methods and MaterialsThe National Cancer Database was queried for women with International Federation of Gynecology and Obstetrics Stage II uterine endometrioid carcinoma who underwent hysterectomy followed by adjuvant RT without chemotherapy. The χ2 tests were performed to compare differences in outcome by type of adjuvant RT (external beam radiation therapy [EBRT] alone, vaginal brachytherapy [VBT] alone, or combination of EBRT and VBT). Overall survival (OS) was assessed by Kaplan–Meier and log-rank tests. Univariate and multivariate analyses were performed to identify predictors of OS. ResultsWe identified 2681 women. Simple hysterectomy was performed on 2261 women (84%). Adjuvant EBRT, VBT, and combination RT were administered to 27%, 36%, and 37%, respectively. There was a statistically significant difference in OS by modality of adjuvant RT (p = 0.01) favoring women who received VBT alone or in combination with EBRT. The 5-year OS was 80%, 87%, and 83% for women who received EBRT, VBT, and combination RT, respectively (p = 0.001). On multivariate analysis, old age, African-American race, no or fewer number of examined lymph nodes, and higher tumor grade were independent predictors of worse OS. RT modality did not sustain its independent prognostic significance as a predictor of OS. ConclusionsIn this nationwide hospital-based study of women with International Federation of Gynecology and Obstetrics Stage II uterine endometrioid carcinoma, adjuvant VBT alone provided excellent survival outcomes and may be a reasonable adjuvant RT modality for properly selected women with adequate lymph node dissection and low-grade tumors.

BRMS1 Expression in Surgically Resected Lung Adenocarcinoma Predicts Future Metastases and IsAssociated with a Poor Prognosis.

Expression of breast cancer metastasis suppressor 1 gene (BRMS1) is decreased in NSCLC cells and tumors. We hypothesized that intratumoral breast cancer metastasis suppressor 1 (BRMS1) expression is associated with lung adenocarcinoma (LUAD) histologic subtypes and overall survival (OS) and disease-free survival (DFS) in patients undergoing resection for early-stage LUAD. Patients (N= 1030) who underwent complete resection for LUAD with tissue available for histologic evaluation were identified. Tissue microarrays were constructed, and immunostaining was performed and scored for intensity of BRMS1 expression. OS and DFS were estimated (by the Kaplan-Meier method) and compared between groups (by the log-rank test), stratified by stage. Hazard ratios (HRs) for hazard of death and recurrence were estimated using univariable and multivariable Cox proportional hazards models. OS and DFS nomograms were created, and model performance was examined. Intratumoral BRMS1 expression was high in 632 patients (61%) and low in 398 (39%). Low BRMS1 expression was associated with higher pathologic T stage (p= 0.001), larger tumor size (p ≤ 0.0001), greater lymphatic (p= 0.032) and vascular (p= 0.001) invasion, LUAD histologic subtype (p= 0.001), and intermediate and high architectural tumor grade (p= 0.003). Low BRMS1 expression was an independent predictor of worse OS (HR= 1.35, 95% confidence interval: 1.10-1.65, p= 0.004) and DFS (HR= 1.27, 95% confidence interval: 1.05-1.54, p= 0.012). OS and DFS nomograms showed excellent predictive performance based on discrimination and calibration. Among patients with surgically resected LUAD, OS and DFS were significantly worse in cases with low intratumoral BRMS1 expression. Our findings suggest that BRMS1 is an independent biomarker with prognostic significance in surgically resected LUAD.

The Effect of Treatment Package Time in Head and Neck Cancer Patients Treated with Adjuvant Radiation Therapy and Concurrent Systemic Therapy

In patients with head and neck squamous cell carcinoma (HNSCC), the “treatment package time” (TPT), defined as the number of days from surgery to end of adjuvant radiation therapy (RT), has been shown to impact outcomes with TPT above 100 days resulting in worse survival. However, these studies were restricted to cases receiving only adjuvant RT with no data for those receiving concurrent systemic therapy (CRT). We analyzed the influence of TPT on survival endpoints for HNSCC treated by surgery followed by CRT. After IRB approval, we used our institutional database to identify HNSCC cases treated with curative surgical resection followed by CRT. The addition of concurrent systemic therapy was due to the presence of positive margins (PM) and/or extracapsular nodal extension (EC). Those with deficient surgical, pathological or follow up data were excluded. For each case we calculated a provisional risk score (RS) based on NCCN defined adverse features; 2 points each were assigned for PM and EC and 1 point for each of the remaining adverse features (T3/4, N2/3, perineural invasion (PNI) and lympho-vascular invasion (LVI). TPT was assessed by calculating the number of days elapsed between surgery date and the last day of CRT for each case. We used %findcut SAS macro tool to search for the cutoff TPT that was associated with significant overall survival (OS) and recurrence free survival (RFS) benefit. According to the TPT optimal cutoff point two groups were formed and Kaplan-Meier curves, log rank tests as well as univariate and multivariate (MVA) analyses were used to assess OS and RFS. We identified 103 cases that met inclusion criteria treated between 2008 & 2015 with a median follow up time of 59 months. Oropharyngeal tumors (OP) were 43%, oral cavity (OC) 40% and laryngeal 17%. HPV positive disease was detected in 22% of patients (50 % of OP). CRT included platinum and cetuximab that were utilized in 72% & 28%, respectively. Optimal TPT was found to be less than 100 days (n= 62) with significantly better OS (p= 0.011) and RFS (p= 0.043) compared to TPT ≥100 days (n= 41). Also 2 & 5 years OS and RFS were significantly better for TPT <100 days (91% vs. 68% & 74% vs. 46% for OS; p<0.05). Study groups were balanced for all characters except that those with TPT <100 days have more OP location; whereas the other group had higher smoking incidence, OC and T4 tumors (p<0.05). On MVA excluding risk score; EC, LVI & PNI were associated with inferior OS. Nevertheless, when RS was included, after excluding its components; TPT <100 days and high RS were independent predictors for worse OS (p<0.05). T4, EC and high RS were all significantly related to inferior RFS (p<0.05). Shorter treatment package time <100 days is associated with better survival outcomes in HNSCC with high risk features even when systemic therapy is added to adjuvant RT. Thus, multidisciplinary coordinated care must be provided to ensure the earliest start of CRT with minimal treatment breaks.

Patterns of care and outcomes of multi-agent versus single-agent chemotherapy as part of multimodal management of low grade glioma.

For high-risk low-grade gliomas (LGGs), adjuvant radiotherapy (RT) with procarbazine/lomustine/vincristine (PCV) chemotherapy increases overall survival (OS) over RT alone. However, in practice, temozolomide (TMZ) is often used instead of PCV. Using the National Cancer Data Base (NCDB), we provide the first investigation of practice patterns and outcomes of chemoradiotherapy with single-agent chemotherapy (SAC, analogous to TMZ) or multi-agent chemotherapy (MAC, analogous to PCV) for LGG. Patients with high-risk Grade II LGGs were queried in the NCDB. Inclusion was limited to patients treated with definitive RT and chemotherapy. Patients were divided into cohorts receiving SAC or MAC. Kaplan-Meier analysis compared overall survival (OS), and Cox proportional hazards models determined variables independently associated with OS. Of 1029 patients, 989 (96.1%) received SAC, while 40 (3.9%) received MAC. Patients treated more recently (2010-2012) were less likely to receive MAC (p = 0.029). No differences in median OS were observed between patients treated with MAC and SAC (45.3 vs. 59.2 months, p = 0.861). Independent predictors of worse OS included age >40, high Charlson-Deyo index, other governmental/unrecorded insurance status, biopsy only, astrocytoma histology, Western geographical region, and higher income. Substuting MAC with SAC had no impact on OS (p = 0.804). There is a significantly greater utilization of SAC compared to MAC in the US. There were no differences in OS between patients receiving SAC and MAC, nor did this factor impact OS on multivariate analysis, suggesting that the practice of substituting MAC with SAC for management of LGG may not adversely affect outcome.

MP80-14 LYMPH NODE YIELD AS A PREDICTOR OF OVERALL SURVIVAL FOLLOWING REGIONAL LYMPHADENECTOMY FOR PENILE CANCER

You have accessJournal of UrologySexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease III1 Apr 2017MP80-14 LYMPH NODE YIELD AS A PREDICTOR OF OVERALL SURVIVAL FOLLOWING REGIONAL LYMPHADENECTOMY FOR PENILE CANCER Chad Ritch, Nachiketh Soodana Prakash, Varsha Sinha, Diana M Lopategui, Katherine Almengo, Micheal Ahdoot, David Alonzo, Mahmoud Alameddine, Sanoj Punnen, Dipen Parekh, and Mark Gonzalgo Chad RitchChad Ritch More articles by this author , Nachiketh Soodana PrakashNachiketh Soodana Prakash More articles by this author , Varsha SinhaVarsha Sinha More articles by this author , Diana M LopateguiDiana M Lopategui More articles by this author , Katherine AlmengoKatherine Almengo More articles by this author , Micheal AhdootMicheal Ahdoot More articles by this author , David AlonzoDavid Alonzo More articles by this author , Mahmoud AlameddineMahmoud Alameddine More articles by this author , Sanoj PunnenSanoj Punnen More articles by this author , Dipen ParekhDipen Parekh More articles by this author , and Mark GonzalgoMark Gonzalgo More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2519AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES There is limited data to define an appropriate threshold for lymph node yield (LNY) following regional lymphadenectomy (rND) for penile squamous cell carcinoma (pSCC) and, whether that specific threshold impacts overall survival (OS). We sought to determine whether a specific LNY affects OS following rND for pSCC and, to define the minimum beneficial number of lymph nodes (LN) to retrieve. METHODS Using the National Cancer Database (NCDB), we identified men diagnosed with pSCC, who underwent rND, from 2004 to 2013. We excluded men diagnosed on autopsy or at the time of death, with preoperative chemotherapy or radiotherapy, M+ disease, and with < 3 months of follow up. We assessed the statistical distribution of LNY following rND. A multivariable logistic regression model was developed to assess predictors of OS including: age, comorbidity, race, stage, grade, nodal status, and LNY. Kaplan-Meier (KM) survival analysis was performed to compare OS by varying thresholds of LNY. RESULTS 938 men with pSCC underwent rND. Of these 452 met inclusion criteria. Median follow up was 29.9 months. The median number of regional LN retrieved was 16. Based on the statistical distribution of LNY and, sensitivity analysis, a threshold of 15 LNs appeared to be clinically and statistically relevant. There was no significant difference in race, stage, grade for men with LNY ≤15 vs >15. However, men with LNY ≤ 15 were older than those with LNY >15 (64 vs 58 years, p<0.01). On multivariable analysis, significant independent predictors of worse OS were: age (HR: 1.02; CI [1-1.03], p<0.05), N+ disease (HR: 3.06; CI [2.12-4.42], p<0.001), and LNY ≤ 15 (HR: 1.62; CI [1.17-2.24], p<0.01). Men with a LNY ≤ 15 demonstrated a significantly decreased 5-year OS compared to those with LNY > 15 (50% VS 73%, p<0.05). On subgroup analysis of men with T2, N0, LNY >15 trended toward better 5-year OS vs LNY ≤15 (90% VS 71%, p=0.06) (Figure) CONCLUSIONS LNY following rND for pSCC appears to have an impact on OS independent of age, stage, nodal status and grade. A minimum LNY >15 following rND may have a beneficial impact on OS and may serve as the quantitative threshold for defining an adequate rND. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1086 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Chad Ritch More articles by this author Nachiketh Soodana Prakash More articles by this author Varsha Sinha More articles by this author Diana M Lopategui More articles by this author Katherine Almengo More articles by this author Micheal Ahdoot More articles by this author David Alonzo More articles by this author Mahmoud Alameddine More articles by this author Sanoj Punnen More articles by this author Dipen Parekh More articles by this author Mark Gonzalgo More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Prognostic value of circulating tumor DNA in patients with colon cancer: Systematic review.

The application of circulating tumor DNA(ctDNA) represents a non-invasive method for tumor detection. Its prognostic significance in patients with colorectal cancer is controversial. We performed a systematic review of data from published studies to assess the prognostic values of ctDNA in patients with colorectal cancer. We searched Medline, Embase, Web of Science, the Cochrane Library, and Scopus databases to identify eligible studies reporting disease-free survival (DFS) and overall survival (OS) stratified by ctDNA prior to December 6, 2016. We evaluated the quality and design of these studies. A total of 22 studies were eligible for systematic review. Among them, 11 studies investigated the prognostic value of ctDNA on disease-free survival (DFS). Seven of 11 studies showed that ctDNA was an independent variable to estimate the probability of DFS by multivariate analyses. Thirteen studies assessed the relationship between ctDNA and overall survival (OS). Eight of 13 studies showed that ctDNA was an independent predictor of worse OS through the use of multivariate analyses. This analysis provides evidence that ctDNA may be a prognostic biomarker, negatively correlated with the survival of patients with colorectal cancer.

Leukocytosis and neutrophilia predicts outcome in anal cancer

ObjectiveLeukocytosis and neutrophilia could be the tip of the iceberg in the inflammatory tumor microenvironment. We aimed to validate their prognostic significance in a cohort of patients treated with definitive chemoradiation for anal squamous cell carcinoma (SCC). Materials & methodsClinical records from all consecutive patients treated in a single institution between 2006 and 2016 with curative-intent radiotherapy were retrospectively analyzed. Leukocytosis and neutrophilia, defined as leukocyte or neutrophil count over 10,000 and 7500/mm3, respectively, were studied in terms of overall survival (OS), progression (PFS), locoregional (LFS) and distant (DFS)-free survival. ResultsWe identified 103 non-metastatic HIV-negative patients, with concurrent chemotherapy use in 78%. Twelve and 8% displayed baseline leukocytosis and neutrophilia, respectively. Estimated 3-year OS and PFS were 88% and 67%, respectively. In univariate analysis, both leukocytosis and neutrophilia were strongly associated with inferior OS, PFS, LFS and DFS (p<0.01). In multivariate analysis, leukocytosis and neutrophilia remained strongly associated with patient outcome (p<0.01), independently from tumor T and N-stage. Anemia was an independent predictor of worse OS and PFS, while chemoradiation overall treatment time below 50days improved PFS. ConclusionLeukocytosis and neutrophilia are strong prognostic factors for OS, PFS, LFS and DFS in anal cancer treated with chemoradiation. These biomarkers could help identify patients with higher risk of tumor relapse that require treatment intensification.

Comparison of the prognostic impact of pre- and post-operative CA19-9, SPan-1, and DUPAN-II levels in patients with pancreatic carcinoma

BackgroundAlthough serum carbohydrate antigen 19-9 (CA19-9), s-pancreas antigen-1 (SPan-1), and duke pancreatic monoclonal antigen type 2 (DUPAN-II) are commonly utilized tumor markers in pancreatic ductal adenocarcinoma (PDAC), it is still unclear which is the most useful for predicting prognosis after surgical resection. Here, we aimed to compare the prognostic impact of pre- and post-operative serum CA19-9, SPan-1, and DUPAN-II levels in patients with resectable PDAC. MethodsPre-operative CA19-9, SPan-1, and DUPAN-II levels were analyzed to compare their prognostic values for resectable PDAC in 198 patients whose pre-operative tumor markers were available. The relationships of clinicopathological factors, including pre- and postoperative CA19-9, SPan-1, and DUPAN-II levels, with overall survival (OS) were analyzed using univariate and multivariate analyses in 149 patients for whom both pre- and postoperative tumor markers were available. ResultsElevated pre-operative CA19-9 (≥37 U/mL), SPan-1 (≥30 U/mL), and DUPAN-II (≥150 U/mL) levels were found in 113 (60%), 96 (51%), and 82 (43%) patients, respectively. In multivariate analysis, absence of adjuvant chemotherapy (hazard ratio [HR], 4.17; p = 0.001), R1 resection (HR, 1.90; p = 0.03), higher histological grade (HR, 1.99; p = 0.02), advanced UICC T factor (HR, N/A; p = 0.04) and elevated postoperative CA19-9 (HR, 3.39; p = 0.009) were identified as independent predictors for worse OS. ConclusionWhen the prognostic impacts of pre- and post-operative serum CA19-9, SPan-1, and DUPAN-II levels in patients with resectable PDAC were compared, elevated postoperative CA19-9 was the strongest predictive marker of poor survival in the pre- and post-operative period.

Role of Monocyte Count and Neutrophil-to-Lymphocyte Ratio in Survival of Oral Cancer Patients.

Introduction Inflammation seems to play a critical role in the development and progression of numerous cancers. Peripheral blood leukocyte count is an easily assessable parameter of systemic inflammatory response. Objective The aim of this study was to investigate whether the pretreatment leukocyte counts can predict the prognosis of patients with oral cavity cancer. Methods Medical records of 471 oral cavity cancer patients diagnosed between January 2007 and December 2008 were retrospectively analyzed. Receiver operating characteristic curve analysis and Cox proportional hazards analyses were applied to evaluate the associations of leukocyte counts with overall survival. Results The overall five year's survival of the cohort was found to be 49.4%. On univariate analysis, elevated monocyte count (≥500/mm3) and neutrophil-to-lymphocyte ratio (NLR) (>2.38) were associated with poor overall survival (OS) (p = 0.001 and 0.000, respectively). Multivariate Cox proportional hazard analysis showed that higher monocyte and NLR levels were significant independent predictors of worse OS (HR = 1.385, 95% CI = 1.049 - 1.829; p < 0.05 and HR = 1.392, 95% CI = 1.045 - 1.855; p < 0.05, respectively). The advanced overall stage and lymph nodal involvement were also independent indicators for poor OS. Conclusions Higher pretreatment monocyte and NLR levels are independent predictors of poor prognosis for patients with oral cavity cancer. Thus, these easily accessed variables can serve as a potent marker to predict the outcomes of oral cancer patients.