Independent Prognostic Factor For Outcome Research Articles

Expression of EIF5A2 associates with poor survival of nasopharyngeal carcinoma patients treated with induction chemotherapy.

BackgroundNasopharyngeal carcinoma (NPC) is a type of head-neck cancer with a distinguishable geographic and racial distribution worldwide. Increasing evidence supports that the accumulation of additional genetic and epigenetic abnormalities is important in driving the NPC tumorigenic process. In this study, we aim to investigate the association between EIF5A2 (Eukaryotic translation initiation factor 5A2) expression status and NPC clinical outcomes.MethodsThe expression status of EIF5A2 was investigated in the NPC tissue microarray. Tissues were from 166 NPC patients staging II-IV, collected between 1999 and 2005. All patients were administered 2–3 cycles of DDP (cisplatin) + 5-Fu (5-fluorouracil) induction therapy and then treated with a uniform conventional two-dimensional radiotherapy. Cell motility assay, tumor growth assay and cytotoxicity assay were performed on the EIF5A2 overexpressed cells and control cells. siRNA was also used in the in vitro studies.ResultsPositive staining of EIF5A2 was observed in 85.4 % (105/123) informative tumor cases. Multivariate analyses demonstrated that EIF5A2 was an independent prognostic marker of poor overall survival (OS) (P = 0.041), failure-free survival (FFS) (P = 0.029), and distant failure-free survival (D-FFS) (P = 0.043) in patients with locoregionally advanced NPC patients treated with cisplatin + 5-Fu chemoradiotherapy. The forced expression of EIF5A2 in NPC cells enhanced the cells’ motility and growth ability. Knock-down of EIF5A2 in NPC cells decreased the cell’s motility and growth ability. Our results also demonstrated that EIF5A2 overexpression induced chemoresistance of NPC cells to 5-Fu.ConclusionsOur findings suggested that EIF5A2 expression, as examined by immunohistochemistry, could function as an independent prognostic factor of outcomes in NPC patients with cisplatin + 5-Fu chemoradiotherapy. EIF5A2 might be a novel therapeutic target for the inhibition of NPC progress.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2714-2) contains supplementary material, which is available to authorized users.

Measurement of liver iron concentration by superconducting quantum interference device biomagnetic liver susceptometry validates serum ferritin as prognostic parameter for allogeneic stem cell transplantation

There are conflicting data regarding the role of serum ferritin (SF) as surrogate parameter for iron overload as an independent prognostic factor for outcome after allogeneic stem cell transplantation (SCT). Superconducting quantum interference device (SQUID) biomagnetic liver susceptometry, a noninvasive measurement of iron overload, allows measurement of the interference of an exteriorly applied small but highly constant magnetic field by the paramagnetic liver storage iron. By measuring the true iron load of patients through SQUID, we wanted to assess the effect of iron overload on patients undergoing SCT. We conducted a single-center retrospective analysis (1994-2010), comparing the effect of SF and liver iron content measured by SQUID shortly before transplantation on overall survival (OS), event-free survival (EFS), and transplant-related mortality (TRM) in 142 patients (median age 54.5 yr, range 5.6-75 yr) undergoing SCT (80% reduced intensity regimen). Patients were subdivided into five groups: myelodysplastic syndrome, de novo acute myeloid leukemia (AML), secondary AML, primary myelofibrosis, and others. Correlation between SF and SQUID was significant (r = 0.6; P < 0.001; log function). The chance of infection was increased 2.4-fold (95% CI 1.22-4.71) when SQUID values ranged ≥1000 μg Fe/g liver (P = 0.012). We found similar results for SF >1000 ng/mL (P = 0.003). A significant association between SQUID and fungal infection was also seen (P = 0.004). For patients with SQUID ≥1000, the risk of proven fungal infection was increased 3.08-fold (95% CI 1.43-6.63). A similar association between SF >1000 and fungal infection was shown (P = 0.01). In univariate analysis, age was a prognostic factor for TRM (P = 0.034, HR 1.04, CI 1.00-1.08). SF ≥1000 was associated with OS (P = 0.033, HR 2.09, CI 1.06-4.11) and EFS (P = 0.016, HR 2.15, 95% CI 1.15-4.10). In multivariate analysis on EFS, only age and SF >1000 remained as independent factors (HR 1.027, P = 0.040, 95% CI 1.001-1.054 and HR 2.058, P = 0.034, 95% CI 1.056-4.008, respectively). The multivariate analysis on TRM left age and SQUID values ≥1000 in the final model (HR 1.045, P = 0.041, 95% CI 1.002-1.090 and HR 2.110, P = 0.103, 95% CI 0.859-5.183, respectively). Our data confirmed that SF ≥1000 increases the risk of infection, moreover fungal infection in transplant recipients. As SQUID values correlate well with SF, we could show that SF is indeed a good surrogate parameter for iron overload when measured shortly before SCT. Prospective trials are needed to investigate the effect of iron chelation before or during SCT on transplant outcome.

Depression and Oropharynx Cancer Outcome.

Studies have shown a modest relationship between depression and mortality in patients with cancer. Our study addressed methodological weaknesses in the literature by restricting the sample to patients with one cancer type, adjusting for factors known to affect outcome, and following up patients for a sufficient period. We prospectively followed patients newly diagnosed with squamous cell oropharyngeal cancer from the start of radiation therapy until death or until date of last clinical visit. All patients were optimally treated with radiation and sometimes chemotherapy. After adjusting for tumor stage, treatment, comorbidities, smoking, excessive alcohol use, and demographic factors, we assessed the effects of baseline self-reported depression on overall survival and recurrence. One hundred thirty participants were followed for a median of 5 years. The average age was 56 years, and 83% were male. Eighteen participants died during the study and 15 experienced disease recurrence. Self-reported depression was associated with decreased overall survival duration (hazard ratio = 3.6, 95% confidence interval = 1.2-10.8) and disease recurrence (hazard ratio = 3.8, 95% confidence interval = 1.2-12.2) in multivariate analysis. In addition, smoking was associated with disease recurrence. Patients with oropharyngeal cancer may benefit from depression screening and evidence-based treatments, if appropriate. Future studies are needed to determine whether depression is an independent prognostic factor of outcome and to elucidate biobehavioral mechanisms involved in patients with oropharyngeal cancer.

Age-specific changes in intrinsic breast cancer subtypes: a focus on older women.

Breast cancer (BC) is a disease of aging and the number of older BC patients in the U.S. is rising. Immunohistochemical data show that with increasing age, the incidence of hormone receptor-positive tumors increases, whereas the incidence of triple-negative tumors decreases. Few data exist on the frequency of molecular subtypes in older women. Here, we characterize the incidence and outcomes of BC patients by molecular subtypes and age. Data from 3,947 patients were pooled from publicly available clinical and gene expression microarray data sets. The PAM50 algorithm was used to classify tumors into five BC intrinsic subtypes: luminal A, luminal B, HER2-enriched, basal-like, and normal-like. The association of age and subtype with recurrence-free survival (RFS), overall survival, and disease-specific survival (DSS) was assessed. The incidence of luminal (A, B, and A+B) tumors increased with age (p < .01, p < .0001, and p < .0001, respectively), whereas the percentage of basal-like tumors decreased (p < .0001). Among patients 70 years and older, luminal B, HER2-enriched, and basal-like tumors were found at a frequency of 32%, 11%, and 9%, respectively. In older women, luminal subtypes had better outcomes than basal-like and HER2-enriched subtypes. After controlling for subtype, treatment, tumor size, nodal status, and grade, increasing age had no impact on RFS or DSS. More favorable BC subtypes increase with age, but older patients still have a substantial percentage of high-risk tumor subtypes. After accounting for tumor subtypes, age at diagnosis is not an independent prognostic factor for outcome.

The prognostic effect of perineural invasion in esophageal squamous cell carcinoma.

BackgroundPerineural invasion (PNI) is correlated with adverse survival in several malignancies, but its significance in esophageal squamous cell carcinoma (ESCC) remains to be clearly defined. The objective of this study was to determine the association between PNI status and clinical outcomes.MethodsWe retrospectively evaluated the PNI of 433 patients with ESCC treated with surgery between 2000 and 2007 at a single academic center. The resulting data were analyzed using Spearman’s rank correlation, the Kaplan-Meier method, Cox proportional hazards regression modeling and Harrell’s concordance index (C-index).ResultsPNI was identified in 209 of the 433 (47.7%) cases of ESCC. The correlation analysis demonstrated that PNI in ESCC was significantly correlated with tumor differentiation, infiltration depth, pN classification and stage (P < 0.05). The five-year overall survival rate was 0.570 for PNI-negative tumors versus 0.326 for PNI-positive tumors. Patients with PNI-negative tumors exhibited a 1.7-fold increase in five-year recurrence-free survival compared with patients with PNI-positive tumors (0.531 v 0.305, respectively; P < 0.0001). In the subset of patients with node-negative disease, PNI was evaluated as a prognostic predictor as well (P < 0.05). In the multivariate analysis, PNI was an independent prognostic factor for overall survival (P = 0.027). The C-index estimate for the combined model (PNI, gender and pN status) was a significant improvement on the C-index estimate of the clinicopathologic model alone (0.739 v 0.706, respectively).ConclusionsPNI can function as an independent prognostic factor of outcomes in ESCC patients, and the PNI status in primary ESCC specimens should be considered for therapy stratification.

Sustained Erythroid Response Associated With Red Cell Transfusion and Progressive Growth Factor Independence Is Feasible With Adjuvant Sertraline In Low-Risk Myelodysplastic Syndrome (LR-MDS)

BackgroundLR-MDS is a heterogeneous group of clonal marrow disorder associated with ineffective hematopoeisis and complex genomic etiology. For patients (pt) with refractory cytopenia phenotype (RC-P), transfusion and growth factor support, such as Erythropoietin Stimulating Agents (ESAs) and Granulocyte Colony Stimulating Factor (G-CSF), are treatment options. Response rates for ESA is about 30%, (and response potentiation can be achieved in about 35% of pt receiving concurrent G-CSF.However, ESA unresponsiveness is a common phenomenon and is associated with transfusion dependence, normal/high EPO levels, and high IPSS score. Therefore, novel therapies are greatly needed. Biologically, LR-MDS is linked to deregulation of apoptosis and cytokine signaling pathways. Selective Serotonin Reuptake Inhibitors (SSRIs) can induce normalization of deranged cytokines such as IL6 and TNF-α in clinical depression. In animal model of arthritis, sertraline abrogates manifestation of autoimmune arthritis by reducing TNF α. Our group recently showed that significant improvement in overall survival (OS) can be achieved in low-risk MDS patients treated with SSRIs, such as sertraline, which is independent of concurrent MDS directed therapy. (Li, et al. ASH 2012 abstract # 3818) Here, we report a case of sequential reversal of transfusion and growth factor dependence phenotype in a pt with refractory anemia multi-lineage dysplasia LR- MDS. MethodsA 72-year male with transfusion dependent refractory anemia (8 units RBC in 8 weeks) was evaluated in clinic. His bone marrow showed erythroid and megakaryocytic dysplasia consistent with RCMD by WHO 2008 classification. Cytogenetic study revealed 45;X-Y[4];46 XY[16]. R-IPSS=1.5 (Cytogenetic=0; blast [0%] =0; Hb=7g/dL=1.5; Platelets [135000] =0; ANC [1500] =0). EPO and ferritin levels were 449 IU/L and 1600 NG/ML, respectively. R-H-EPO was administered at 40000 IU subcutaneously (SQ) per week. In view of severe depression, pt initiated sertraline at 100 mg orally on day (D) 61 of treatment. Response after 12 weeks of ESA, sequential addition of G-CSF and sertraline, were assessed according to internal working group (IWG) 2006 criteria. ResultsAfter 3 months of standard weekly SQ ESA (D1-D92) (Fig.1), and given ESA refractoriness, G-CSF at 480 mcg SQ 5-times weekly was added (ESA + G-CSF schedule) (D92-D189).Transfusion independence was observed by D 161 of combined ESA+G-CSF(Fig.1). Progressive hemoglobin stabilization resulted in G-CSF dose reduction to twice a week from D189 –D 257 (Fig. 1). Sequential resolution of ESA dependence was observed from D257- D515. Over the treatment period, the absolute increase in Hb level was 4.2 g/dL from baseline. Restoration of ESA erythroid response was observed by D93-210 after G-CSF and sertraline addition. (Table. 1) Sustained and improved Hb levels were achieved after 200 days of G-CSF discontinuation and ESA dose de-escalation while on sertraline treatment. [Display omitted] ConclusionsReversal of transfusion dependence represents a critical step in treatment algorithm of LR-MDS pt presenting with refractory anemia. In this context, ferritin normalization has previously been recognized as independent prognostic factor for outcome in MDS. Our case suggests feasibility of restoration of ESA sensitivity with concurrent G-CSF+ sertraline, and evidence for sustained beneficial effect of sertraline while ESA de-escalation, which seems independent from G-CSF. The MDS disease modifying effect of sertraline in LR- MDS patient presenting with refractory anemia and experiencing ESA refractoriness should be evaluated in prospective trials. Disclosures:No relevant conflicts of interest to declare.

ASTRO 2013

ASTRO 2013

Serum Sarcosine is a Risk Factor for Progression and Survival in Patients with Metastatic Castration-Resistant Prostate Cancer

Sarcosine has been identified as a differential metabolite that is greatly increased during progression from normal tissue to prostate cancer and metastatic disease. In this study we assessed the role of serum sarcosine in metastatic castration-resistant prostate cancer (mCRPC) patients. Data from 52 mCRPC patients treated with docetaxel-based chemotherapy were retrospectively analyzed. Receiver operating characteristic curves, and Kaplan-Meier and Cox multivariate analyses were performed. Median sarcosine values were significantly higher in mCRPC versus non-mCRPC patients (0.81 vs 0.52 nmol/µl; p < 0.0001). A significant correlation resulted between serum sarcosine levels and the duration of hormone sensitivity (Spearman's correlation coefficient: -0.51; p = 0.001). At multivariate analysis sarcosine was an independent prognostic factor of outcome in terms of overall and progression-free survival. Serum sarcosine values were significantly increased in patients with metastatic disease. Moreover, this biomarker is a risk factor for progression and survival in chemotherapy-treated mCRPC patients.

Outcomes of treatment for relapsed acute lymphoblastic leukaemia in children with Down syndrome

Children with Down syndrome (DS) have a greater risk for developing both acute lymphoblastic leukaemia (ALL) and significant adverse effects of chemotherapy. We investigated their outcome with, and tolerance of, treatment protocols for relapsed ALL optimized in the paediatric population without DS. Probability of survival and causes of treatment failure were determined for 49 children with DS and a matched cohort of 98 children without DS among 2160 children treated for relapsed ALL in clinical trials conducted by the Berlin-Frankfurt-Münster ALL Relapse Study Group between 1983 and 2012. Despite more favourable ALL relapse characteristics, children with DS experienced lower event-free (EFS) and overall survival (OS) than the control group without DS (EFS 17±08% vs. non-DS 41±06%, P=0·006; OS 17±09% vs. non-DS 51±06%, P<0·001). Children with DS developed more frequently fatal complications of treatment (34±07% vs. non-DS 10±04%, P<0·001). During the last decade, EFS and OS were no longer significantly different in children with and without DS (EFS 31±09% vs. 36±09%, P=0·399; OS 31±12% vs. 53±09%, P=0·151). DS proved an independent prognostic factor of outcome after ALL relapse. Induction deaths and treatment-related mortality but not subsequent relapse were the main barrier to successful outcomes of relapse therapy in children with DS.

Quantitative proteome analysis of overexpressed Cripto-1 tumor cell reveals 14-3-3γ as a novel biomarker in nasopharyngeal carcinoma

We previously found that Cripto-1 is involved in the tumorigenesis of nasopharyngeal carcinoma (NPC). Here, to identify new NPC related proteins and to investigate the clinicopathological correlations of it in NPC, Cripto-1 over-expressed cell (CNE1/CR1(+)) was established. Two-dimensional difference in gel electrophoresis (2D-DIGE) analysis and matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF MS) were used to identify 23 differential proteins in CNE1/CR1(+) and parental cells. Among them, 14-3-3γ showed the potential to be a NPC related protein. 14-3-3γ expression was found in 58.3% (60/103) tumor tissues as detected by IHC, and 69.6% (16/23) NPC fresh tumors expressed higher 14-3-3γ than paired non-cancerous tissues as detected by Western blot. Moreover, 14-3-3γ expression was positively correlated with N classification (p=0.031), distant metastasis (M classification, p=0.018) and clinical stage (p=0.046) of NPC patients. As determined by the Kaplan-Meier method, 14-3-3γ expression in NPC was significantly associated with overall survival (p=0.015). Multivariate analysis also showed that the expression of 14-3-3γ protein was an independent prognostic factor for outcome of NPC. In this study, we identified upregulated 14-3-3γ by 2D-DIGE in CNE1/CR-1(+). We also demonstrated that 14-3-3γ might be a potential biomarker for the prognosis of patients with NPC. We believe that three aspects of this manuscript will make it interesting to general readers of Journal of Proteomics. Firstly, based on our previous report, we further validated that Cripto-1 can promote the proliferation and invasion of nasopharyngeal carcinoma (NPC). In this context, we used 2D-DIGE to identify new NPC related proteins. As a result, 14-3-3γ showed the potential to be a candidate. Secondly, we reported for the first time that the expression level of 14-3-3γ was significantly increased in human NPC patient tissues, and 14-3-3γ overexpression correlated statistically with N classification, distant metastasis, and clinical stage. Our results highlight the clinical significance of 14-3-3γ in NPC. Finally, we found that high 14-3-3γ expression is associated with poor survival in NPC patients. Thus, this study has identified that the 14-3-3γ involves in the carcinogenesis of NPC. Our findings may also provide new insights into understanding the molecular mechanism involved in NPC carcinogenesis and progression, and may lead to the development of new approaches for effective diagnosis and therapy.

Outcome of Treatment for Relapsed Acute Lymphoblastic Leukemia in Children with Down Syndrome

AbstractAbstract ▪669▪This icon denotes a clinically relevant abstract Background.Children with Down syndrome (DS) have a higher risk for developing not only acute lymphoblastic leukemia (ALL) but also significant adverse effects of chemotherapy compared to the overall pediatric population. Currently, it is unknown how children with DS, who develop a relapse of ALL, respond to treatment protocols that were optimized in the pediatric population without DS. We hypothesized that a concomitant diagnosis of DS is an independent prognostic factor of survival after treatment for relapsed ALL and that decreased tolerance of therapy impairs the success of relapse treatment in children with DS. Patients and Methods.The probability of event-free (EFS) and overall survival (OS) and the causes of treatment failure were determined for 51 children with DS and a matched cohort of 102 children without DS among 2736 children and young adults (up to 22 years of age) who were treated for relapsed ALL on a series of clinical trials conducted by the ALL-REZ-BFM Study Group between 1983 and 2012. Results.Among children with DS, who were enrolled on clinical trials of the ALL-REZ-BFM Study Group, ALL relapse more frequently exhibited favorable prognostic characteristics compared to the unmatched population of 2579 patients without DS. High risk forms of relapse were less frequent among children with DS (risk group S4, 10 vs. 28%, p<0.001) including relapse at a very early and early time point (35 vs. 56%, p<0.001). A higher proportion of relapse in DS involved the bone marrow (94 vs. 83% p<0.001). Transcripts of ETV6-RUNX1 or BCR-ABL1 were detected in none of the cases of relapsed ALL in DS compared to 20% (231/895, p<0.001) and 6% (83/1379, p=0.02) of cases in the population without DS. Treatment for relapsed ALL in children with DS less frequently included irradiation (of the central nervous system or total body) and hematopoietic stem cell transplantation compared to the matched non-DS group (28 vs. 70%, p<0.001, and 15 vs. 40%, p=0.002), respectively. Despite the apparent favorable risk profile, EFS and OS were lower in children with DS than the matched control group without DS (EFS 16 ± 08% vs. 39 ± 06%, p=0.005; OS 17 ± 08% vs. 48 ± 06%, p<0.001). Fatal adverse events of treatment developed more frequently in children with DS than the control group (36 ± 07% vs. 9 ± 03%, p<0.001). In contrast, the cumulative incidence of a subsequent relapse was similar in both groups (32 ± 07%, DS vs. 36 ± 05%, non-DS, p=0.373). The proportion of children with DS registered on clinical trials for relapsed ALL after frontline treatment on ALL-BFM trials showed an increase over time (from 1 registered vs. 1 non registered patient in ALL-BFM 81 to 18 registered vs. 8 non registered patients in ALL-BFM 2000). Furthermore, the proportion of patients with high risk relapse features (S4 group) and DS increased from 5 to 15%. During the more recent study period (2000–2012) EFS and OS were no longer significantly different in children with and without DS (EFS 30 ± 09% vs. 35 ± 09%, p=0.403; OS 30 ± 11% vs. 51 ± 08%, p=0.158).DS was an independent prognostic factor of outcome after relapse of ALL in multivariate analysis. Conclusion.A higher rate of induction deaths and treatment-related mortality was the main barrier to successful outcomes of relapse therapy in children with DS whereas relapse rates were not different from patients without DS. An increased representation of children with DS including those with high risk features in recent time suggests that access to clinical trials for relapsed ALL has been successfully broadened for children with DS. Specific optimization of treatment modifications and supportive care have improved survival in children with DS and are suggested to further decrease the number of fatal treatment-related events during relapse therapy in this group. Disclosures:No relevant conflicts of interest to declare.

Wpływ wybranych czynników kliniczno-morfologicznych na wyniki leczenia chorych z zawansowanym rakiem krtani

IntroductionThe aim of the study was to indicate independent prognostic factors of treatment in group of patients with advanced cancer of the larynx. Material and methodThe paper presents results of univariate and multivariate analysis of selected clinical and morphological factors in the group of 355 patients with advanced laryngeal cancer treated in the ENT Clinical Department in Zabrze in the following years 1998–2007. The analysis of the results of treatment in relation to clinical and morphological features of the tumor was based on overall survival, disease-free survival, local control and locoregional control. The results of analysis allowed to indicate the independent prognostic factors for outcome in patients with advanced laryngeal cancer. ResultsUnivariate analysis showed that the increase of clinical advancement of laryngeal cancer was associated with worse prognosis, as well as the fact that the primary location of the tumor in supraglottis and infiltration in laryngeal part of pharynx determined the worse outcome. Univariate and multivariate analysis confirmed that the number of lymph node metastases in the surgical specimen and microscopic radical of surgery were the most important prognostic factors for survival and cure in the study group. ConclusionThe strongest independent prognostic significance for all efficacy criteria have: completeness of operation and number of metastatic lymph nodes.

P-0041 The Prognostic Significance of Perineural Invasion in Patients of Gastric Cancer

IntroductionPerineural invasion (PNI) is the process of neoplastic invasion of nerves and is an under-recognized route of metastatic spread. Data from a large retrospective research suggest that PNI could function as an independent prognostic factor of outcomes in colorectal cancer (CRC) and PNI status should be considered in primary CRC specimens for therapy stratification. In this study we try to evaluate the prognostic significance of PNI in gastric cancer patients. MethodsThis study included gastric cancer patients who had undergone curative gastrectomy in our institution from January 2000 to December 2006. Pathological sections were stained with hematoxylin and eosin. Tumors were re-reviewed for PNI by a pathologist blinded to the patients' outcomes. PNI was assessed as positive when cancer cells in close proximity to nerve and involving at least 33% of its circumference or tumor cells within any of the 3 layers of the nerve sheath. The relationship between PNI positivity and other clinicopathological factors were analyzed using Chi-square test. Survival analysis and curves were established according to the Kaplan–Meier method and compared by the log-rank test. Multivariate analysis to assess the role of PNI and other clinicopathological features as prognostic factors were performed by the Cox regression analysis. ResultsPNI was positive in 121 of the 292 patients (41.44%). pTNM stage, tumor size, tumor differentiation, Borrmann classification and blood vessel invasion were closely associated with the presence of PNI. However, PNI was not related to age, sex, tumor location and resection type. The 5-year overall survival rate was 41.3% for PNI-positive tumors versus 77.8% for PNI-negative tumors (P<0.05). In patients with negative-lymph node, the 5-year overall survival rate was 68.8% for PNI-positive ones versus 96.5% for PNI-negative ones (P<0.05). Univariate analysis showed that overall survival was affected by many factors including perineural invasion. However, on multivariate analysis, PNI was not indicated as an independent prognostic factor for overall survival. ConclusionFor the whole group of patients and the node-negative patients, the overall survival of PNI positive patients was significantly shorter than that of PNI negative patients. PNI is an indicator of cancer aggressiveness. However, multivariate analysis did not show PNI was an independent prognostic factor for gastric cancer patients with curative gastrectomy. [Display omitted]

Clinicopathologic prognostic factors in childhood atypical teratoid and rhabdoid tumor of the central nervous system

The objective of this study was to describe the clinical and pathologic features and to identify prognostic factors in patients with atypical teratoid/rhabdoid tumors (AT/RT) of the central nervous system (CNS). Patients aged <18 years with newly diagnosed CNS AT/RT who were treated in France between 1998 and 2008 were retrospectively identified. The study included all patients who had a diagnosis of AT/RT confirmed by pathologic review, including immunostaining for INI 1, tumor protein 53 (p53), β-catenin, claudin-6, and Ki-67 and analysis for SMARCB1/hSNF5/INI1 mutation. Fifty-eight patients with confirmed AT/RT were eligible for the current analysis. The median age at diagnosis was 1.4 years (range, 14 days to 8.5 years). The site of the primary tumor was supratentorial in 26 patients, infratentorial in 28 patients and spinal in 4 patients. Loss of INI1 nuclear expression was observed in 49 of 50 evaluable tumors. Positive claudin-6 was observed in 37 of 42 assessed tumors and, in 12 of those tumors, the staining was strong and diffuse. Positive nuclear immunoreactivity for β-catenin was observed in 24 of 44 tumors, and P53 was overexpressed in 31 of 44 tumors. Primary adjuvant therapy included chemotherapy in 47 patients and radiotherapy in 16 patients. The median follow-up was 58 months (range, 9-125 months), and the median survival was 9 months. Multivariate analysis identified age <2 years (P = .01), metastasis at diagnosis (P = .03), and strong immunopositivity for claudin-6 (P = .03) as prognostic factors for the risk of death. AT/RT tumors in children carry a dismal prognosis. Age <2 years, metastasis at diagnosis, and strong claudin-6 positivity appeared to be independent prognostic factors for outcome.

Measurement of Liver Iron Concentration by Quantum Interference Device Biosusceptometry (SQUID) Validates Serum Ferritin As Prognostic Parameter for Allogeneic Stem Cell Transplantation

Abstract 1018 Introduction:There is conflicting data regarding the role of serum ferritin (SF) as an independent prognostic factor for outcome after allogeneic stem cell transplantation (allo-SCT). SF is a surrogate parameter for iron overload and - as an acute phase-protein - can be confounded by many factors. An independent, non-invasive measurement of iron overload is needed. Determining iron content through SQUID correlates well with results of liver biopsies (Nielsen et al. 1998). This method measures the interference of an exteriorly applied small but highly constant magnetic field by the paramagnetic liver storage iron of the patient. Methods:We conducted a single-center retrospective analysis from October 1994 to December 2012, comparing the effect of SF and liver iron content measured by SQUID shortly before transplantation on overall survival (OS), event-free survival (EFS) and transplant-related mortality (TRM) in 143 patients (median age 40 years) undergoing allo-SCT (73% reduced intensity regimen). The diagnoses were subdivided into 4 groups: myelodysplastic syndrome, secondary acute myeloid leukemia (AML), primary myelofibrosis, primary AML and other. Statistical calculations employed Pearson's correlation, ordinal logistic regression, Cox regression analysis and multiple Cox regression analyses with backward elimination. Results:Correlation between SF and SQUID showed a highly significant result of r=0.5 (p < 0.001). The chance of infection was increased 2.4-fold (CI 1.22,4.71) when SQUID values ranged > 1000 μg Fe/g liver. We found similar results for SF > 1000 ng/ml (p 0.003), where the risk of infection was increased 2.87–fold (CI 1.43;5.78). A significant association between SQUID und fungal infection was also seen (p 0.004). For patients with SQUID > 1000 the chance of proven fungal infection versus fungal infection of all other categories was increased 3.08-fold (CI 1.43,6.63). Similarly an association between SF > 1000 and fungal infection could be demonstrated (p 0.001), with a 4.04-fold increased chance of proven fungal infection versus lower fungus categories for patients with SF values > 1000. There was no association between continuous SQUID-, respectively SF values and VOD (veno-occlusive disease) or acute GvHD. The following variables were significantly related with OS: chronic GvHD (HR 0.326, CI 0.13–0.83, p 0.019,), sepsis (p 0.002, HR 2.94 CI 1.48–5.83), new onset cardiac abnormalities (p 0.001, HR 3.21, CI 1.64–6.27), SF > 1000 (p 0.033, HR 2.09, CI 1.06–4.11). For EFS we found statistically significant results for chronic GvHD (p 0.040, HR 0.45, CI 0.21–0.97), sepsis (p 0.012, HR 2.35, CI 1.21–4.58), cardiac abnormalities (p 0.001, HR 2.81, CI 1.50–5.29), SF > 1000 (p 0.016, HR 2.15, CI 1.15–4.10) and time to engraftment (p 0.038, HR 0.934, CI 0.89–1.00). For TRM, statistically significant results were found for sepsis (p 0.005, HR 3.23, CI 1.43–7.29), cardiac abnormalities (p < 0.001, HR 5.21, CI 2.41–11.27), and age (p 0.034, HR 1.04, CI 1.00–1.08). Fungal infection of all categories was not statistically significant (p=1,101), but proven fungal infection in comparison with no fungal infection was found significant (p 0.018, HR 3.12, CI 1.22–7.99. In the multivariate analysis SF and SQUID (categorical and continuous) were not significant factors for OS, EFS or TRM. Conclusion:Our data confirmed previous publications that SF > 1000 increases the risk of infection, moreover fungal infection. In the univariate analysis it is significantly associated with OS and EFS during allo-SCT. As SQUID values correlate well with SF, we could show that SF is indeed a good surrogate parameter for iron overload when measured shortly before allo-SCT. We are now in need of prospective trials investigating the effect of iron chelation before or during allo-SCT on transplant outcome. [Display omitted] [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Neurogenesis in colorectal cancer is a marker of aggressive tumor behavior and poor outcomes.

Colorectal cancer staging criteria do not rely on examination of neuronal tissue. The authors previously demonstrated that perineural invasion is an independent prognostic factor of outcomes in colorectal cancer. For the current study, they hypothesized that neurogenesis occurs in colorectal cancer and portends an aggressive tumor phenotype. In total, samples from 236 patients with colorectal cancer were used to create a tissue array and database. Tissue array slides were immunostained for protein gene product 9.5 (PGP9.5) to identify nerve tissue. The correlation between markers of neurogenesis and oncologic outcomes was determined. The effect of colorectal cancer cells on stimulating neurogenesis in vitro was evaluated using a dorsal root ganglia coculture model. Patients whose tumors exhibited high degrees of neurogenesis had 50% reductions in 5-year overall survival and disease-free survival compared with patients whose tumors contained no detectable neurogenesis (P = .002 and P = .006, respectively). Patients with stage II disease and high degrees of neurogenesis had greater reductions in 5-year overall survival and disease-free survival compared with lymph node-negative patients with no neurogenesis (P = .002 and P = .008, respectively). Patients with stage II disease and high degrees of neurogenesis had lower 5-year overall survival and disease-free survival compared with patients who had stage III disease with no neurogenesis (P = .01 and P = .008, respectively). Colorectal cancer cells stimulated neurogenesis and exhibited evidence of neuroepithelial interactions between nerves and tumor cells in vitro. Neurogenesis in colorectal cancer appeared to play a critical role in colorectal cancer progression. Furthermore, the current results indicated that neurogenesis functions as an independent predictor of outcomes and may play a role in therapy stratification for patients with lymph node-negative disease.

526 ESTABLISHMENT OF AN INTERPHASE FISH TEST FOR PREDICTION OF PROGNOSIS IN CLEAR CELL RENAL CELL CARCINOMA

You have accessJournal of UrologyKidney Cancer: Evaluation and Staging1 Apr 2011526 ESTABLISHMENT OF AN INTERPHASE FISH TEST FOR PREDICTION OF PROGNOSIS IN CLEAR CELL RENAL CELL CARCINOMA Jimsgene Sanjmyatav, Martin Mühr, Doriana Sava, Sophie Matthes, Maria Sternal, Heiko Wunderlich, Thomas Steiner, Marc-Oliver Grimm, and Kerstin Junker Jimsgene SanjmyatavJimsgene Sanjmyatav Jena, Germany More articles by this author , Martin MührMartin Mühr Jena, Germany More articles by this author , Doriana SavaDoriana Sava Jena, Germany More articles by this author , Sophie MatthesSophie Matthes Jena, Germany More articles by this author , Maria SternalMaria Sternal Jena, Germany More articles by this author , Heiko WunderlichHeiko Wunderlich Jena, Germany More articles by this author , Thomas SteinerThomas Steiner Jena, Germany More articles by this author , Marc-Oliver GrimmMarc-Oliver Grimm Jena, Germany More articles by this author , and Kerstin JunkerKerstin Junker Jena, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1250AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES By precise mapping of genomic imbalances of 56 clear cell renal cell carcinomas using array-CGH in our previous studies we identified specific chromosomal aberrations which are significantly associated both with metastasis and cancer specific survival. In multivariate analysis gains of 1q21.3 and of 20q11.21–q13.2 as well as loss of 9p21.3–p24.1 were independent predictors for metastasis. Multivariate Cox-regression analysis revealed gains of 7q36.3 and of 20q11.21–q13.32 and a loss of 9p21.3–p24.1 as independent prognostic factors for outcome of patients. The aim of this study was to prove the prognostic value of these aberrations using FISH probes on these critical regions in order to develop a routine diagnostic tool. METHODS FISH experiments were performed on isolated cell nuclei from tumor tissues. The same cohort of previous array-CGH analysis was used for these experiments (32 metastasized and 24 non-metastasized). For each critical chromosomal region (1q21.3, 7q36.3, 9p21.3–p24.1 und 20q11.21–q13.32) we hybridized a mixture of three different commercially available FISH probes: region specific probe in red dye, centromeric probe of corresponding chromosome or probe close to centromere in green dye and centromeric probe of chromosome 2 in blue colour as control. 100 nuclei were scored in each case. RESULTS Loss of 9p21.3–p24.1 (Fisher's exact test; p=0.017) and gains of 1q21.3 (p=0.030), 7q36.3(p=0.019) and 20q11.21–q13.32 (p=0.008) displayed significant correlations with metastasis occurrence. Our analysis revealed significant correlation of gains 7q36.3 (p=0.001) and 20q11.21–q13.32 (p=0.05) as well as loss of 9p21.3-p24.1 (p=0.00002) with cancer specific death. Patients with tumours harbouring these aberrations in more than 30% of cells have a poor outcom. CONCLUSIONS FISH results confirmed our previous findings of array-CGH and showed that these regions play an important role in cancer progression. Based on these genetic targets it seems possible to design a combined FISH assay which can be used in routine diagnostics for outcome prediction of patients with ccRCC. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e214 Peer Review Report Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jimsgene Sanjmyatav Jena, Germany More articles by this author Martin Mühr Jena, Germany More articles by this author Doriana Sava Jena, Germany More articles by this author Sophie Matthes Jena, Germany More articles by this author Maria Sternal Jena, Germany More articles by this author Heiko Wunderlich Jena, Germany More articles by this author Thomas Steiner Jena, Germany More articles by this author Marc-Oliver Grimm Jena, Germany More articles by this author Kerstin Junker Jena, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Long-Term Results of Liver Resection in the Treatment of Patients with Hepatocellular Carcinoma

The aim of the study was the analysis of the results of liver resection in the treatment of patients with hepatocellular carcinoma, taking into consideration the selected factors based on the department's material. Data of 122 patients subject to liver resection due to hepatocellular carcinoma at the Department of General, Transplantation and Liver Surgery, Medical University of Warsaw, were subject to retrospective analysis. The influence of selected factors on the long-term treatment results was determined, and the patient survival depending on the tumor stage as per the TNM scale was compared. The statistical significance threshold was set at p = 0.05. 1- and 3-year overall survival and recurrence-free survival in the whole patient group was 82.1% and 56.3%, and 57.7% and 20.1%, respectively. The perioperative mortality rate was 1.6%. The neoplasm advancement exceeding the first stage on the TNM scale was associated with lower values of overall survival (p = 0.001, HR = 3.7) and recurrence-free survival (p = 0.00008, HR = 3.8). Elevation of AFP was the only independent prognostic factor for overall survival (p = 0.04, HR = 1.04 at alpha-fetoprotein levels > 1000 ng/ml), while the presence of neoplastic emboli in small blood vessels was an independent risk factor for HCC recurrence (p = 0.02, HR = 2.24). The alpha-fetoprotein levels and presence in the histopathological examination of neoplastic emboli in small blood vessels are independent prognostic factors for outcome of patients operated for hepatocellular carcinoma. The diagnosis of neoplasm at stage 1 as per TNM significantly improves long-term results of resective treatment.

Perineural Invasion Is an Independent Predictor of Outcome in Colorectal Cancer

Perineural invasion (PNI) is associated with decreased survival in several malignancies, but its significance in colorectal cancer (CRC) remains to be clearly defined. We evaluated PNI as a potential prognostic indicator in CRC, focusing on its significance in node-negative patients. We identified 269 consecutive patients who had CRC resected at our institution. Tumors were re-reviewed for PNI by a pathologist blinded to the patients' outcomes. Overall and disease-free survivals were determined using the Kaplan-Meier method, with differences determined by multivariate analysis using the Cox multiple hazards model. Results were compared using the log-rank test. PNI was identified in less than 0.5% of the initial pathology reports. On rereview, 22% of tumors in our series were found to be PNI positive. The 5-year disease-free survival rate was four-fold greater for patients with PNI-negative tumors versus those with PNI-positive tumors (65% v 16%, respectively; P < .0001). The 5-year overall survival rate was 72% for PNI-negative tumors versus 25% for PNI-positive tumors. On multivariate analysis, PNI was an independent prognostic factor for both cancer-specific overall and disease-free survival. In a subset analysis comparing patients with node-negative disease with patients with stage III disease, the 5-year disease-free survival rate was 56% for stage III patients versus 29% for patients with node-negative, PNI-positive tumors (P = .0002). Similar results were seen for overall survival. PNI is grossly underreported in CRC and could serve as an independent prognostic factor of outcomes in these patients. PNI should be considered when stratifying CRC patients for adjuvant treatment.

Age as prognostic factor in osteosarcoma

10537 Background: Osteosarcoma may occur at all ages but has a distinct age distribution from 10 to 20 years old. Several retrospective studies of osteosarcoma suggest a favourable outcome for children compared to adults. To evaluate whether age is indeed related to outcome, we retrospectively analyzed patients with osteosarcoma under the age of forty. Furthermore, we retrospectively analyzed whether outcome of osteosarcoma in young adult patients is different when treatment took place in a pediatric or an adult oncology department. Methods: Patients with primary osteosarcoma treated in our hospital between 1978 and 2008 were included in this study. To evaluate the role of age, patients were divided in two groups: less than 20 and 20 - 40 years of age. Prognostic factors including histological response after neoadjuvant chemotherapy, were analyzed using Cox regression multivariate analysis. Results: In total, 102 patients with primary osteosarcoma were included. Overall survival (OS) of the whole population was 50.7% with a 5-years event-free survival of 47.1%. Age markedly affected survival with an OS of 61.1% in patients below 20 years of age and 38.6% in the patient group between twenty and forty years (p=0.014). There was no significant difference in prognostic factors, such as presence of metastasis at diagnosis. Pediatric patients under the age of 10 had a superior OS of 71.4% (p =0.02) compared to patients older than 10 years. Overall survival of patients aged 14–20 years was not significant different when treated in a pediatric oncology department as compared to treatment in an adult department (57.9% vs. 47.4%, p= 0.705) . Osteosarcoma patients older than 20 years, showed a worse histologic response to pre-operative chemotherapy and experienced more toxicity. Dose reduction due to toxicity was applied in 20.8% of adults vs. in 1.9% (p=0.002) of the children. Conclusions: Based on the results found in this study, we conclude that age is an independent prognostic factor for outcome of patients with primary osteosarcoma. No significant financial relationships to disclose.