5-year On Overall Survival Rates Research Articles

Readmissions after Umbilical Cord Blood Transplantation and Impact on Overall Survival

Patients treated with allogeneic hematopoietic stem cell transplantation (SCT) have high rates of readmission, but the incidence after umbilical cord blood transplantation (UCBT) is poorly described. The goal of this study was to identify the incidence and risk factors for readmission after UCBT and the impact of readmission on overall survival (OS). A retrospective review of patients receiving a UCBT at Dana-Farber/Brigham and Women's Hospital between January 1, 2004 and December 31, 2013 was performed. The readmission rates 30 days after discharge from the UCBT admission and at day +100 after the UCBT were examined. Reasons for readmission, as well as sociodemographic, disease-, and SCT-related variables were evaluated. Predictors of readmission and the impact of readmission on OS were identified using multivariate regression analysis. Of patients who received a UCBT, 42 of 126 patients (33.3%) were readmitted within 30 days of discharge and 57 of 123 patients (46.3%) were readmitted by day +100 after transplantation. The most common causes for readmission were infection (38.3%), fever without a source (14.8%), and graft-versus-host disease (8.6%). Infection during the index admission was the only significant risk factor for readmission at both time points in a univariate and multivariate regression analysis (OR, 11.66; 95% CI, 2.77 to 49.13; P < .01 and OR, 5.4; 96% CI, 1.87 to 15.58; P < .01). Prior radiation therapy was also associated with an increased risk of readmission at both time points in the multivariate regression model (OR, 20.6; 95% CI, 3.53 to 120.04; P ≤ .01 and OR, 5; 95% CI, 1.21 to 20.71; P = .03). The multivariate regression model also showed that black race and a median income of <60,000 in the patient's home zip code increased the risk of readmission by day +100 (OR, 30.17; 95% CI, 1.33 to 684.48; P = .03 and OR, 2.88; 95% CI, 1.04 to 7.8; P = .04, respectively). After adjusting for age, disease type, and the disease status at transplant, OS was reduced for the patients who were readmitted by day +100 (HR, 2.44; 95% CI, 1.46 to 4.06; P < .01). There was also a trend toward decreased survival in patients readmitted 30 days after discharge (HR, 1.58; 95% CI, .96 to 2.6; P = .07). Readmissions are common after UCBT. Infections and fever without a source are the most common causes of readmission. Being readmitted by day +100 resulted in a lower 5-year OS rate as compared with patients who were not readmitted. Prior radiation and infection during the transplant admission resulted in increased risk of readmission by 30 days and day +100. Similarly, race and socioeconomic status predicted readmission by day +100. Further understanding of the mechanisms leading to readmissions in these groups may allow for identification of interventions that could reduce readmissions and thus improve mortality.

Impact of facility volume on outcomes in patients with squamous cell carcinoma of the anal canal: Analysis of the National Cancer Data Base.

Given the rarity of anal cancer and the technical aspects involved in radiation (RT) planning, the authors conducted a population-based analysis evaluating the impact of radiation oncology facility volume on overall survival (OS) in patients with squamous cell carcinoma (SCC) of the anal canal. The National Cancer Data Base (NCDB) was queried for patients with SCC of the anal canal who underwent RT. All patients were coded as having received their entire course of RT at the NCDB reporting facility. Facility volume was categorized into tertiles (low, intermediate, and high) and was based on the number of times a facility's unique identification code appeared. In total, 13,550 patients were identified. Patients who received treatment at higher volume radiation oncology facilities had longer OS based on multivariate analysis (MVA) (hazard ratio, 0.81; 95% confidence interval [CI], 0.73-0.90; P < .001) and propensity score matching analysis (hazard ratio, 0.79; 95% CI, 0.69-0.91; P < .001). For patients who received treatment at low-volume, intermediate-volume, and high-volume centers, the 5-year OS rate was 70%, 72.2%, and 75.4%, respectively (P < .001). Compared with low/intermediate-volume radiation oncology centers, high-volume centers were more likely to treat patients with concurrent chemotherapy (odds ratio, 1.27; 95% CI, 1.07-1.51; P = .006) and less likely to have treatment delays leading to an RT duration of >45 days (odds ratio, 0.74; 95% CI, 0.69-0.80; P < .001). Treatment at higher volume radiation oncology centers appears to be associated with improved OS in patients with SCC of the anal canal. These results likely reflect the relation between physician experience and delivery of high-quality RT, which perhaps is best evident in rare tumors such as anal SCC. Cancer 2017;123:228-236. © 2016 American Cancer Society.

Prognostic Value of Lymph Node Ratio in Locally Advanced Rectal Cancer Patients After Preoperative Chemoradiotherapy Followed by Total Mesorectal Excision.

Although the absolute number of positive lymph nodes (LNs) has been established as 1 of the most important prognostic factors in rectal cancers, many researchers have proposed that the lymph node ratio (LNR) may have better predicted outcomes. We conducted a retrospective study to compare the predictive ability of LNR and ypN category in rectal cancer.A total of 264 locally advanced rectal cancer (LARC) patients who underwent preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME) between 2005 and 2012 were reviewed. All patients were categorized into 3 groups or patients with metastatic LNs were categorized into 2 groups according to the LNR. The prognostic effect on overall survival (OS) and disease-free survival (DFS) was evaluated.With a median follow-up of 45 months, the OS and DFS were 68.4% and 59.3% for the entire cohort, respectively. The respective 5-year OS and DFS rates for the 3 groups (LNR = 0, 0 < LNR ≤ 0.20, and 0.20 < LNR ≤ 1.0) were as follows: 83.2%, 72.6%, and 49.4% (P < 0.001) and 79.5%, 57.3%, and 33.5% (P < 0.001), respectively. Multivariate analysis revealed that LNR and differentiation, but not the number of positive LNs, had independent prognostic value for OS (hazard ratio [HR] = 2.328, 95% confidence interval [CI]: 1.850–4.526, P < 0.001) and DFS (HR = 3.004, 95% CI: 1.616–5.980, P < 0.001). As for patients with positive LNs, the respective 5-year OS and DFS rates for the 2 groups (0 < LNR ≤ 0.20, and 0.20 < LNR ≤ 1.0) were 72.6% and 49.4% (P < 0.001) and 57.3% and 33.5% (P < 0.001), respectively. Multivariate analysis revealed that only LNR was an independent factor for OS (HR = 3.214, 95% CI: 1.726–5.986, P < 0.001) and DFS (HR = 4.230, 95% CI: 1.825–6.458, P < 0.001). Subgroups analysis demonstrated that the ypN category had no impact on survival whereas increased LNR was a significantly prognostic indicator for worse survival in the LNs < 12 subgroup.LNR is an independent prognostic factor in LARC patients treated with preoperative CRT followed by TME. It may be a better independent staging method than the number of metastatic LNs when <12 LNs are harvested after preoperative CRT.

Retrospective Analysis of the Impact of Treatment on Prognosis in 44 Adolescents and Young Adult Patients with Acute Lymphoblastic Leukemia

To study the clinical characteristics and the impact of treatment on prognosis in 44 adolescents and young adult (AYA) patients with acute lymphoblastic leukemia. Clinical data of 44 AYA ALL patients admitted in our hospital from September 1997 to April 2014 were analyzed retrospectively and the impact of treatment on overall survival (OS) and event free survival (EFS) were investigated. The median age of the patients at diagnosis was 23.7 (15-37) years and the male/female was 2.38:1. Out of them 88.6% of patients achieved complete remission (CR) after 1 course of induction chemotherapy, 35 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 6 patients received chemotherapy, 3 patients received autologous hematopoietic stem cell transplantation (auto-HSCT) as consolidation therapy in CR1. The expected 3-year OS and EFS rates of all the 44 patients were 64.3% and 61.7% respectively. The expected 5-year OS and EFS rates were 55.4% and 56.6% respectively. Allo-HSCT was not superior to chemotherapy and auto-HSCT in all the 44 patients (P = 0.308 for OS and P = 0.291 for EFS). In allo-HSCT group, the treatment related mortality was 22.9%, and the differences of OS and EFS in standard risk and poor risk AYA ALL patients were no significant (P = 0.775 for OS and P = 0.817 for EFS). However, compared with chemotherapy and auto-HSCT, allo-HSCT could significantly improve the OS and EFS in standard risk AYA ALL (P = 0.0296 for OS and P = 0.0359 for EFS). Allo-HSCT as consolidation therapy may provide survival improvement for standard risk AYA ALL. However, further prospectively randomized clinical study is warranted to confirm whether allo-HSCT is an optimal treatment for AYA ALL, which is still controversial at present.

Reduced PLCG1 expression Is Associated with Inferior Survival in Myelodysplastic Syndromes

The PLCG1 gene encodes phospholipase C g isoform, which is involved in diverse physiological and pathological cellular processes through catalyzing the hydrolysis of phosphatidylinositol 4,5-bisphosphate to produce the second messenger molecules inositol 1,4,5-trisphosphate and diacylglycerole. Until now, roles of phospholipase C g 1 in hematopoiesis have been shown in animal models. Plcg1 deficient mouse lacks erythropoiesis and die in early embryonic stage. In zebrafish model, it was demonstrated that phospholipase C g 1 is required in granulocyte maturation. Physiological and/or pathological role of phospholipase C g 1 in human hematopoiesis has not been elucidated. In human, the PLCG1 gene is located on long arm of chromosome 20. Deletion of long arm of chromosome 20 (del(20q)) is commonly observed in myelodysplastic syndromes (MDS). Previously, we determined the common deleted region (CDR) of del(20q) in MDS, and the PLCG1 gene is located within the CDR. Reduced expression of genes located in the CDR due to haploinsufficiency may play role in molecular pathogenesis of MDS. Therefore, we analyzed PLCG1 expression in bone marrow mononuclear cells in MDS patients with or without del(20q), and investigated its clinical significance in the present study.Mononuclear cells separated from bone marrow samples taken at the time of diagnosis with written informed consent from patients were used. To analyze PLCG1 expression, quantitative RT-PCR was performed. Total RNA was extracted from mononuclear cells and subjected to cDNA synthesis. Real-time RT-PCR was carried out using cDNA as template by the TaqMan probe method (Applied Biosystems) with co-amplification of the endogenous control gene, human GAPDH (Applied Biosystems) were performed. The human PLCG1 primer-probe set was from Applied Biosystems. A total of 109 MDS patients, 65 males and 44 females with median age of 69 years (range: 22-91 years), with (n=20) or without (n=89) del(20q), were included in the present study. They were classified as RCUD (n=11), RCMD (n=55), RARS (n=11), RAEB-1 (n=16), and RAEB-2 (n=16) according to WHO classification. They were categorized in four IPSS risk groups, low risk (n=21), intermediate-1 risk (n=52), intermediate-2 risk (n=20), and high risk (n=6).Relative PLCG1 expression level was significantly reduced in MDS patients with del(20q) compared to control subjects (n=20) (P=0.011). Median values of relative PLCG1 expression level in MDS patients with del(20q) and control subjects were 0.94 and 1.96. In addition, relative expression level of PLCG1 in whole MDS cohort significantly lower than that in control subjects (P=0.046). Expression patterns of PLCG1 among, were not different. Median values of relative PLCG1 expression level in five WHO-subtypes, RCUD, RCMD, RARS, RAEB-1, and RAEB-2 were 1.50, 1.55, 1.29, 1.13, and 1.12, respectively, but no statistically difference was observed. WHO-subtypes with high blast counts (RAEB-1 and RAEB-2) showed trend in association with reduced PLCG1 expression compared with those with low blast counts (RCUD, RCMD, and RARS) (median value: 1.01 vs. 1.54, P =0.11). To investigate prognostic implication of PLCG1 expression in MDS, we analyzed impact of PLCG1 expression on overall survival (OS). Based on PLCG1 expression level, 109 patients were divided into four groups, high (Q1), intermediate (Q2, Q3), and low (Q4) quartiles. Kaplan-Meier analysis demonstrated that the lowest quartile (Q4) showed significantly worse survival compared with remaining quartiles (Q1-Q3) (P =0.0015). The estimated 5-year OS rates in Q1-3 group and Q4 group were 63.2% and 29.7%, respectively. Percentage of patients with WHO-subtypes with high blast count (RAEB-1 and RAEB-2) was significantly higher in Q4 than other quartiles (46.9% vs 22.1%, P =0.019 by Fisher's exact test).The present study demonstrated that reduced PLCG1 expression is associated with inferior clinical outcome, indicating that PLCG1 expression could be a useful prognostic marker in MDS. Association between reduced PLCG1 expression and WHO-subtypes with high blasts counts, suggesting that PLCG1 dysfunction play a role in disease progression. DisclosuresNo relevant conflicts of interest to declare.

Expression of ezrin in oral squamous cell carcinoma: Prognostic impact and clinicopathological correlations.

There have been few investigations into the effects of ezrin expression in oral squamous cell carcinoma (OSCC). The aim of this study was to analyze the influence of ezrin expression on the prognosis of patients with OSCC. Eighty patients were included in the retrospective study. Expression and localization of ezrin were evaluated using immunohistochemistry. Associations were identified using χ² tests. Prognostic factors were identified by univariate and multivariate analysis. Seventy-six (95%) patients showed ezrin expression. Ezrin expression had a significant impact on overall survival (OS) (p < 0.001). With increasing expression, the 5-year OS rate dropped from 100% for ezrin-negative patients to 47% for patients with high expression. Multivariate analysis confirmed the significant influence of ezrin expression on OS (p = 0.011). Cytoplasmic localization of ezrin led to a significantly lower survival rate in comparison with membranous expression. Ezrin may serve as a biomarker that predicts biologically aggressive behavior of OSCC and hence improves therapeutic techniques and the prognosis of patients affected with the disease.

Correlation Between Tumor Regression Grade and Clinicopathological Parameters in Patients With Squamous Cell Carcinoma of the Esophagus Who Received Neoadjuvant Chemoradiotherapy.

The aim of this study was 2-fold: first, to assess the prognostic significance on overall survival (OS) of the 3-point tumor regression grade (TRG) in patients with esophageal squamous cell carcinoma (ESCC) who received neoadjuvant chemoradiotherapy (nCRT); second, to investigate the associations of TRG with the clinicopathological characteristics of the study patients.A total of 357 ESCC patients were retrospectively enrolled. The 3-point TRG was determined by assessing the percentage of viable residual tumor cells (VRTC) in the resected specimens as follows: TRG 1, 0% VRTC; TRG 2, 1% to 50% VRTC; and TRG 3, >50% VRTC.A TRG of 1, 2, and 3 was found in 32.2%, 38.9%, and 28.9% of the specimens, respectively. High TRG values were significantly associated with advanced pretreatment clinical stage, longer tumor length, and higher posttreatment tumor depth of invasion (yT), the presence of lymph node metastases (LNM), and lymphovascular invasion. We observed a stepwise decrease in 5-year OS rates with increasing TRG, as follows: 51% for patients with a TRG of 1, 28% for patients with a TRG of 2, and 22% for patients with a TRG of 3 (P < 0.001). TRG and LNM were independent predictors of OS in multivariate analysis. Notably, the prognostic impact of TRG on OS was greater in patients without LNM (P < 0.001) and ypT3 disease (P = 0.021).TRG is independently associated with OS in ESCC patients treated with nCRT. The interrelationships between TRG, LNM, and depth of tumor invasion may improve the prognostic stratification in esophageal cancer.

Metachronous Second Primary Malignancies after Head and Neck Cancer in a Korean Cohort (1993-2010).

Second primary malignancy (SPM) is the major long-term cause of patient mortality with head and neck squamous cell carcinoma (HNSCC). As the incidence of high-risk human papillomavirus (HPV)-related HNSCC is increasing globally, we analyzed the patterns of SPM occurrence, the effect of the index tumor site along with attributes to HPV, and the effect of SPM on survival in South Korean patients with head and neck cancer (HNC). Data were retrieved from the Korea Central Cancer Registry, a nationwide population-based cancer registry, from 1993 to 2010. Standardized incidence ratios were analyzed and compared between index tumor sites, particularly oropharyngeal vs. non-oropharyngeal sites. After adjustment for competing risks, 3- and 5-year SPM rates were calculated using the cumulative incidence function. The effects of SPM occurrence on overall survival (OS) were then analyzed. SPM rates were significantly lower for HPV-attributable oropharyngeal sites than for non-oropharyngeal sites, such as the larynx and hypopharynx (p<0.001). SPM rates were also lower for oral cavity first primary sites than for non-oropharyngeal first primary sites (p<0.001). SPMs typically occurred in the esophagus, lungs and the head and neck. Uterine cervical cancers occurred significantly more frequently after index oropharyngeal cancer in women. The 5-year and 10-year OS rates were 57.8 and 45.7% in all HNC patients, respectively. The OS after SPM occurrence was poor (5-year, 31.8%; 10-year, 20.8%) compared to after index HNC occurrence (5-year, 68.4%; 10-year, 41.2%). SPM occurrence in the esophagus and lung/bronchus showed a worse OS than SPM localized to the head and neck. South Korean HNC patient, the first primary cancer site affected SPM risk and distribution. The 5- and 10-year OS rates deteriorated after SPM occurrence, particularly in the esophagus and lungs. Further optimization of follow-up strategies for effective surveillance of SPM, particularly in the esophagus and lungs, is warranted.

Influence of late-stage chronic kidney disease on overall survival in patients with upper tract urothelial carcinoma following radical nephroureterectomy

ObjectivesThe prevalence of both chronic kidney disease (CKD) and upper tract urothelial carcinoma (UTUC) in Taiwan is unusually high, and we aimed to investigate the impact of preoperative renal function on UTUC after radical nephroureterectomy. Materials and methodsBetween 2000 and 2013, 248 UTUC patients were enrolled in this retrospective study after excluding patients who had concomitant muscle-invasive bladder cancer, whose tumor metastasized at initial presentation, and who received perioperative chemotherapy or radiotherapy. The significance of CKD on overall survival (OS), cancer-specific survival (CSS), and bladder recurrence-free survival (BRFS) was evaluated by Cox proportional hazard model. ResultsThe median follow-up time was 45.41 months. Overall 5-year OS, CSS, and BRFS rates were 78.27%, 87.81%, and 70.42%, respectively. Aging, late-stage CKD, and nonorgan-confined primary tumor stage were independent predictors for OS after adjustment. Nonorgan-confined primary tumor stage and lymph node involvement were two independent predictors for CSS after adjustment. Concomitant bladder tumor was the only significant predictor for BRFS after adjustment. ConclusionPatients with late-stage CKD had a higher risk of having poor OS. Patients with concomitant bladder tumor had a greater risk of having bladder cancer recurrence despite primary tumor stage. Concomitant bladder tumor, however, had no effect on OS and CSS in this study.

Impact of Beta Blocker on Clinical Outcomes of Multiple Myeloma (MM) Patients

▪Background: A recent preclinical study revealed an antiproliferative and apoptotic effect of propranolol on MM cell lines. This study was to investigate if propranolol and other beta blocker intake improved survival in MM patients.Methods: Among patients seen at Mayo Clinic, Rochester from 1993 to 2010, we identified those taking propranolol. Age, year of diagnosis, International Staging System (ISS), Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) were used as case-match variables to match propranolol users to two control populations: no beta blocker and other beta-blocker. Cox proportional hazard modeling was utilized to analyze the effect of propranolol and other beta blockers intake on overall survival (OS) and disease-specific survival (DSS).Results: In 3 groups: propranolol (n=52), no beta blocker (n= 136), or other beta blocker (n=84), transplant eligibility was 63.5%, 66.9%, 66.7% respectively (p=0.90). Median age was 63 years. Median follow-up was 86 months. No statistically differences were seen in age, ISS, mSMART or year of diagnosis in 3 groups (p=0.46).In univariate analysis comparing propranolol vs no beta blocker or other beta blocker cohort, 5-year OS rate was 60.2% vs 47% or 64% (p=0.039), and 5-year DSS rate was 71.7% vs 50.3% or 69.1% (p=0.0029). In multivariate analysis adjusted for age, ISS, transplant eligibility, mSMART and year of diagnosis, compared to propranolol intake, no beta blocker group had poorer OS [HR= 2.081; 95% CI (1.353- 3.200); p=0.0008], and DSS [HR=2.833 (1.709-4.697); p<0.0001], but other beta blocker users had no difference in OS [HR =1.145 (0.728-1.803);p=0.56],and DSS [HR= 1.276 (0.745-2.185); p=0.38].Conclusion: Propranolol and other beta-blocker intake among MM patients were equally associated with a more favorable OS and DSS. [Display omitted] [Display omitted] DisclosuresLust:Senesco: PI Other.

Clinicopathologic features and oncologic outcomes of colorectal cancer patients with extremely high carcinoembryonic antigen.

The aim of this study is to investigate the clinicopathologic features and oncologic outcomes of colorectal cancer patients with extremely elevated (≥50 ng/mL) preoperative serum carcinoembryonic antigen (CEA) levels. We enrolled 756 primary colorectal cancer patients with elevated preoperative CEA levels (≥5 ng/mL) who underwent surgery between 2004 and 2010 and compared clinicopathologic features according to preoperative CEA levels of 5-50 ng/mL (n = 676) and ≥50 ng/mL (n = 80). The impact of extremely elevated CEA on overall survival (OS) and disease-free survival (DFS) was analyzed using Kaplan-Meier analysis and the Cox proportional hazards model. The median follow-up period was 43 months (range, 0-121). Patients with preoperative CEA ≥50 ng/mL demonstrated higher rates of advanced T stage (97.3 vs. 88.6%, p = 0.016) and distant metastasis (33.8 vs. 17.9%, p = 0.002), but not lymph node metastasis (54.1 vs. 52.2%, p = 0.807). The 5-year OS rate was 69.1%, and the 3-year DFS rate of curatively resected patients (n = 641; 84.8%) was 68.9%. In multivariate analysis, preoperative CEA ≥50 ng/mL, as well as age, N stage, vascular invasion, perineural invasion, post/preoperative CEA ratio ≥0.32, and palliative resection, was an independent predictor of OS. However, for patients treated with curative resection, preoperative CEA ≥50 ng/mL was not significantly associated with DFS or OS (p = 0.053 and 0.157, respectively). Colorectal cancer patients with extremely elevated (≥50 ng/mL) preoperative CEA had advanced disease more frequently but comparable oncologic outcomes if curative resection was performed.

Choroid plexus tumor epidemiology and outcomes: implications for surgical and radiotherapeutic management.

Choroid plexus tumors (CPTs) are rare neoplasms of the central nervous system whose optimal management is not well defined. The Surveillance Epidemiology and End Results (SEER) Database from 1978 to 2009 was queried to define population-based outcomes for all patients with CPTs. Patient demographic data, histological classification (choroid plexus papilloma [CPP], atypical CPP [aCPP], and choroid plexus carcinoma [CPC]), extent of surgery, and use of radiation therapy (RT) as part of an initial course of therapy were analyzed for impact on overall survival (OS) and cause-specific survival (CSS). Chemotherapy data were not available within the SEER database. A total of 349 patients with CPTs were identified (120 CPCs, 26 aCPPs, and 203 CPPs). Patients with CPC presented at a younger age (median 3, mean 14.8 years) relative to CPP (median 25, mean 28.4 years; p < 0.0001). Histology was a significant predictor of OS, with 5-year OS rates of 90, 77, and 58 % for CPP, aCPP, and CPC, respectively. Older age and male sex were prognostic for worse OS and CSS for CPP. Only extent of surgery had a significant impact on survival for CPC. The use of adjuvant RT in patients with CPC undergoing surgery was not associated with a significantly improved OS (p = 0.17). For patients undergoing GTR without RT as part of an initial course of therapy, estimated 5- and 10-year OS were 70 % (±7 %) and 67 % (±8 %), respectively. Prospective data are required to define the optimal combination of surgery with adjuvant therapies, including chemotherapy.

Altered Interphase Fluorescence in Situ Hybridization Profiles of Chromosomes 4, 8q24, and 9q34 in Pancreatic Ductal Adenocarcinoma Are Associated with a Poorer Patient Outcome

Most patients with pancreatic ductal adenocarcinoma (PDAC) die within 6 months of diagnosis. However, 20% to 25% patients undergoing total tumor resection remain alive and disease-free 5 years after diagnostic surgery. Few studies on tumor markers have predicted patient prognosis and/or survival. We evaluated the effect of tumor cytogenetic copy number changes detected by interphase fluorescence in situ hybridization on overall survival (OS) of 55 PDAC patients. The prognostic value of copy number changes showing an effect on OS was validated in an external cohort of 44 surgically resected PDAC patients by comparative genomic hybridization arrays, and the genes coded in altered chromosomes with prognostic value were identified by high-density single-nucleotide polymorphism arrays in 20 cases. Copy number changes of chromosomes 4 and 9q34 with gains of 8q24 were independently associated with shorter OS. On the basis of these three chromosomal alterations, a score is proposed that identifies patients with significantly different (P<0.001) 5-year OS rates: 60%±20%, 16%±8%, and 0%±0%, respectively. Our results show an association between tumor cytogenetics and OS of PDAC patients and provide the basis for further prognostic stratification of patients undergoing complete tumor resection. Further studies to identify specific genes coded in these chromosomes and their functional consequences are necessary to understand the clinical effect of these changes.

Prognostic value of the number of retrieved lymph node and lymph node ratio in locally advanced rectal cancer after preoperative radiation therapy.

582 Background: To assess the prognostic impact of total number of retrieved lymph node (TNN) and lymph node radio (LNR) in patients with locally advanced rectal cancer who received preoperative radiation therapy and surgery Methods: We retrospectively analyzed data from 677 patients with locally advanced rectal cancer who underwent preoperative radiation therapy followed by mesorectal excision at Asan Medical Center between October 1999 and May 2009. The median radiation dose was 50 Gy, and 674 patients (99%) underwent concurrent chemotherapy. All patients were divided into two groups according to the status of lymph node involvement. We assessed the influence of TNN on overall survival (OS) and disease-free survival (DFS) in the patients with node-negative disease (pN0, n = 490), and the prognostic value of LNR, estimated by dividing the number of positive nodes by the number of lymph nodes examined, in the patients with node-positive disease (pN1-2, n = 187). Results: The median follow-up period was 74 months.Patients with pN0 had median 12 lymph nodes examined (range, 0-38). Comparing with patients who had ≤ 8 TNN, patients with &gt; 9 TNN had significantly higher 5-year OS (89% vs. 95%, p = 0.038) and DFS rates (81% vs. 90%, p = 0.013). Multivariate analysis showed that TNN more than 9 was significant prognostic factor for OS (p = 0.032) and DFS (p = 0.007). For patients with pN1-2, patients with low LNR (≤ 0.33, n = 144) showed significantly higher 5-year OS (33% vs. 73%, p &lt; 0.001) and DFS rates (18% vs. 56%, p &lt; 0.001) than high LNR group (&gt; 0.33, n = 43). Also, low LNR was independent prognostic factor for OS (p = 0.001) and DFS (p &lt; 0.001) in multivariate analysis. Conclusions: TNN for node-negative rectal cancer and LNR for node-positive rectal cancer are independent prognostic factors for survival outcome in patients with locally advanced rectal cancer after preoperative radiation therapy. These factors could be considered as useful prognostic indicators irrespective of current TNM staging system.

Risk factors for locoregional recurrence in patients with resected N1 non-small cell lung cancer: a retrospective study to identify patterns of failure and implications for adjuvant radiotherapy

BackgroundMeta-analysis of randomized trials has shown that postoperative radiotherapy (PORT) had a detrimental effect on overall survival (OS) in patients with resected N1 non–small cell lung cancer (NSCLC). Conversely, the locoregional recurrence (LR) rate is reported to be high without adjuvant PORT in these patients. We have evaluated the pattern of failure, actuarial risk and risk factors for LR in order to identify the subset of N1 NSCLC patients with the highest risk of LR. These patients could potentially benefit from PORT.MethodsWe conducted a retrospective study on 199 patients with pathologically confirmed T1–3N1M0 NSCLC who underwent surgery. None of the patients had positive surgical margins or received preoperative therapy or PORT. The median follow-up was 53.8 months. Complete mediastinal lymph node (MLN) dissection and examination was defined as ≥3 dissected and examined MLN stations; incomplete MLN dissection or examination (IMD) was defined as <3 dissected or examined MLN stations. The primary end point of this study was freedom from LR (FFLR). Differences between patient groups were compared and risk factors for LR were identified by univariate and multivariate analyses.ResultsLR was identified in 41 (20.6%) patients, distant metastasis (DM) was identified in 79 (39.7%) patients and concurrent LR and DM was identified in 25 (12.6%) patients. The 3- and 5-year OS rates in patients with resected N1 NSCLC were 78.4% and 65.6%, respectively. The corresponding FFLR rates were 80.8% and 77.3%, respectively. Univariate analyses identified that nonsmokers, ≤23 dissected lymph nodes, visceral pleural invasion and lymph node ratio >10% were significantly associated with lower FFLR rates (P < 0.05). Multivariate analyses further confirmed positive lymph nodes at station 10 and IMD as risk factors for LR (P < 0.05). The 5-year LR rate was highest in patients with both these risk factors (48%).ConclusionsThe incidence of LR in patients with surgically resected T1–3N1M0 NSCLC is high. Patients with IMD and positive lymph nodes at station 10 have the highest risk of LR, and may therefore benefit from adjuvant PORT. Further investigations of PORT in this subset of patients are warranted.

Prognostic Implications Of PRAME Expression Levels In Myelodysplastic Syndromes

The preferentially expressed antigen of the melanoma (PRAME) gene was first identified in melanoma tissue as a tumour-associated antigen recognized by autologous cytotoxic T cells against a melanoma surface antigen. While expression level of PRAME is quite low in most of normal tissues of human, including bone marrow normal CD34+ cells, except for testis, PRAME overexpression is observed in various human cancers, including hematological malignant disorders. Although clinical and biological significance of PRAME expression in human cancers has not been fully elucidated, it has been demonstrated that high PRAME expression is associated poor clinical outcomes in a number of solid cancers. Association between PRAME expression and clinical outcomes in hematological malignancies has not been clarified. In acute myeloid leukemia, high expression of PRAME was shown to be associated with worse progression-free survival or overall survival by some research groups but not by other groups. Our previous study demonstrated that inhibition of PRAME expression in leukemic cells results in cell cycle arrest and induction of apoptosis, suggesting oncogenic function of PRAME expression in leukemogenesis. Clinical significance of PRAME expression in myelodysplastic syndromes (MDS) also has not been fully elucidated. In the present study, we examined PRAME expression of bone marrow cells in MDS patients to clarify clinical significance of PRAME expression.Bone marrow samples of MDS patients were used for analysis. Samples were taken at the time of diagnosis with written informed consent from patients. Total RNA extraction, cDNA synthesis and quantitative real-time RT-PCR by the TaqMan probe method using an ABI 7500 real-time PCR system (Applied Biosystems) with co-amplification of the endogenous control gene, human GAPDH (Applied Biosystems), were performed. Expression levels were obtained using the standard curve method in each experiment, after normalization with the GAPDH gene for each sample in duplicate wells. The human PRAME primer-probe sets were from Applied Biosystems (assay ID: Hs00196132_m1). Data including patients' demographic, disease status, medical history, clinical and laboratory findings, and outcome, were collected from medical records and laboratory data base.A total of 111 MDS patients, 68 males and 43 females with median age of 69 years (range: 20-91 years) were included in the present study. They were classified as RCUD (n=15), RCMD (n=61), RARS (n=8), RAEB-1 (n=15), and RAEB-2 (n=12) according to WHO classification. Based on the IPSS, they were categorized in four risk groups, low risk (n=29), intermediate-1 risk (n=55), intermediate-2 risk (n=23), and high risk(n=4). Expression level of PRAME was varied among the MDS patients analyzed. Median value of relative PRAME expression level of 111 MDS patients and that of 19 control subjects were 0.073 and 0.07, and there was no significant difference in distribution of expression level of PRAME. However, when we compared expression patterns of PRAME among five WHO-subtypes, statistical difference was observed (P=0.0116). Relative PRAME expression level in WHO-subtypes with high blast counts (RAEB-1 and RAEB-2) was significantly higher than that in WHO-subtypes with less blast counts (RCUD, RCMD, RARS) (median value: 0.44 vs. 0.05, P=0.0012). To investigate prognostic implication of PRAME expression in MDS, we analyzed impact of PRAME expression on overall survival (OS). Based on PRAME expression level, 111 patients were divided into two categories, ‘high expression group' (above median value) and ‘low expression group' (below median value). Kaplan-Meier analysis demonstrated that high expression group showed significantly poorer overall survival than low expression group (P=0.0165). The estimated 5-year OS rates in high expression group and low expression group were 63.5% and 78.4%, respectively.The present study demonstrated that high PRAME expression is associated with poorer clinical outcome, indicating that PRAME expression could be a useful prognostic marker in MDS. Biological significance of PRAME expression in MDS is unclear. Expression level of PRAME was higher in WHO-subtypes with high blasts counts, suggesting that PRAME may play role in disease progression in MDS. Further studies should be necessary to clarify clinicopathological and biological significance of PRAME expression in MDS. Disclosures:No relevant conflicts of interest to declare.

Comparison of the prognostic values of various nutritional parameters in patients with esophageal squamous cell carcinoma from Southern China.

Nutritional evaluation is important for patients with esophageal cancer, but the impact of undernutrition on outcome of those patients is not well elucidated. Our aim is to assess the impact of baseline nutritional status on overall survival (OS) in Chinese patients with esophageal squamous cell carcinoma (ESCC) and to detect a most appropriate indicator for nutritional evaluation. 502 patients from Southern China diagnosed as ESCC in Sun Yat-Sen University Cancer Center were included. A series of nutritional indicators were introduced to evaluate the baseline nutritional status. Kaplan-Meier method was used to estimate the 5-year OS and the log-rank test was used to determine the survival differences. Cox proportional hazards model was used in the univariate and multivariate analyses of OS. With a median follow up time of 30 months, the median OS for the entire patient group was 37.3 months with the 5-year OS rate of 43.0%. Only performance status, AJCC 6th stage and body mass index (BMI) were the independent prognostic factors in multivariate analysis of OS. The median OS for patients with BMI less than 18.5, patients with BMI within 18.5-24.9 and patients with BMI more than 24.9 were 19.2, 43.2 and 51.6 months, respectively, with the 5-year OS rates of 25.2%, 46.1% and 48.1% (P<0.001). Patients with BMI <18.5 tended to present with a more advanced stage disease and a poorer tumor grade. Baseline nutritional status is predictive of OS in Chinese patients with ESCC. BMI is a steady indicator for nutritional evaluation and a sensitive prognostic parameter for ESCC patients. Treatment optimization in ESCC patients with low BMI should integrate the modalities and individual nutritional support.

Margin Status Remains an Important Determinant of Survival After Surgical Resection of Colorectal Liver Metastases in the Era of Modern Chemotherapy

To determine the impact of surgical margin status on overall survival (OS) of patients undergoing hepatectomy for colorectal liver metastases after modern preoperative chemotherapy. In the era of effective chemotherapy for colorectal liver metastases, the association between surgical margin status and survival has become controversial. Clinicopathologic data and outcomes for 378 patients treated with modern preoperative chemotherapy and hepatectomy were analyzed. The effect of positive margins on OS was analyzed in relation to pathologic and computed tomography-based morphologic response to chemotherapy. Fifty-two of 378 resections (14%) were R1 resections (tumor-free margin <1 mm). The 5-year OS rates for patients with R0 resection (margin ≥1 mm) and R1 resection were 55% and 26%, respectively (P = 0.017). Multivariate analysis identified R1 resection (P = 0.03) and a minor pathologic response to chemotherapy (P = 0.002) as the 2 factors independently associated with worse survival. The survival benefit associated with negative margins (R0 vs R1 resection) was greater in patients with suboptimal morphologic response (5-year OS rate: 62% vs 11%; P = 0.007) than in patients with optimal response (3-year OS rate: 92% vs 88%; P = 0.917) and greater in patients with a minor pathologic response (5-year OS rate: 46% vs 0%; P = 0.002) than in patients with a major response (5-year OS rate: 63% vs 67%; P = 0.587). In the era of modern chemotherapy, negative margins remain an important determinant of survival and should be the primary goal of surgical therapy. The impact of positive margins is most pronounced in patients with suboptimal response to systemic therapy.

Five Year Results of US Intergroup/RTOG 9704 With Postoperative CA 19-9 ≤90 U/mL and Comparison to the CONKO-001 Trial

Radiation Therapy Oncology Group (RTOG) trial 9704 was the largest randomized trial to use adjuvant chemoradiation therapy for patients with pancreatic cancer. This report analyzes 5-year survival by serum level of tumor marker CA 19-9 of ≤90 vs >90 U/mL and compares results to the those of the CONKO-001 trial. CA 19-9 expression was analyzed as a dichotomized variable (≤90 vs >90 U/mL). Cox proportional hazard models were used to identify the impact of the CA 19-9 value on overall survival (OS). Actuarial estimates of OS were calculated using the Kaplan-Meier method. Both univariate (hazard ratio [HR] = 3.2; 95% confidence interval [CI], 2.3-4.3, P<.0001) and multivariate (HR = 3.1; 95% CI, 2.2-4.2, P<.0001) analyses demonstrated a statistically significant decrease in OS for CA 19-9 serum level of ≥90 U/mL. For patients in the gemcitabine (Gem) treatment arm with CA 19-9 <90 U/mL, median survival was 21 months. For patients with CA 19-9 ≥90 U/mL, this number dropped to 10 months. In patients with pancreatic head tumors in the Gem treatment arm with RT quality assurance per protocol and CA 19-9 of <90 U/mL, median survival and 5-year rate were 24 months and 34%. In comparison, the median survival and 5-year OS rate for patients in the Gem arm of the CONKO trial were 22 months and 21%. This analysis demonstrates that patients with postresection CA 19-9 values ≥90 U/mL had a significantly worse survival. Patients with pancreatic head tumors treated with Gem with CA 19-9 serum level of <90 U/mL and per protocol RT had favorable survival compared to that seen in the CONKO trial. CA 19-9 is a stratification factor for the current RTOG adjuvant pancreas trial (0848).

Lymph node ratio is an independent prognostic factor in patients with rectal cancer treated with preoperative chemoradiotherapy and curative resection

PurposeTo evaluate the prognostic effect of lymph node ratio (LNR) in patients with locally advanced rectal cancer who were treated with curative resection after preoperative chemoradiotherapy (CRT). MethodsBetween October 2001 and December 2007, 519 patients who had undergone curative resection of primary rectal cancer after preoperative CRT were enrolled. Of these, 154 patients were positive for lymph node (LN) metastasis and were divided into three groups according to the LNR (≤0.15 [n=80], 0.16–0.3 [n=44], >0.3 [n=30]) to evaluate the prognostic effect on overall survival (OS) and disease-free survival (DFS). ResultsLNR (≤0.15, 0.16–0.3, and >0.3) was significantly associated with 5-year OS (90.3%, 75.1%, and 45.1%; p<0.001) and DFS (66.7%, 55.8%, and 21.9%; p<0.001) rates. In a multivariate analysis, LNR (≤0.15, 0.16–0.3, and >0.3) was a significant independent prognostic factor for OS (hazard ratios [HRs], 1, 3.609, and 8.197; p<0.001) and DFS (HRs, 1, 1.699, and 3.960; p<0.001). LNR had a prognostic impact on OS and DFS in patients with <12 harvested LNs, as well as in those with ≥12 harvested LNs (p<0.05). ConclusionLNR was a significant independent prognostic predictor for OS and DFS in patients with locally advanced rectal cancer who were treated with curative resection after preoperative CRT.