Potential Predictors Of Survival Research Articles

Predictors of Long-Term Outcome in Patients with Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors After Peptide Receptor Radionuclide Therapy with 177Lu-Octreotate

Outcome analyses for patients with gastroenteropancreatic neuroendocrine tumors (GEP NET) after peptide receptor radionuclide therapy (PRRT) are still limited, especially with regard to the impact of the Ki-67 index. Using a single-center analysis, we aimed to establish predictors of survival. We retrospectively analyzed a consecutive cohort of 74 patients who had metastatic GEP NET and underwent PRRT with (177)Lu-octreotate (mean activity of 7.9 GBq per cycle, aimed at 4 treatment cycles at standard intervals of 3 mo). Patients (33 with pancreatic NET and 41 with nonpancreatic GEP NET) had unresectable metastatic disease graded as G1 or G2 (G1/G2) and documented morphologic or clinical progression within less than 12 mo or uncontrolled disease under somatostatin analog treatment. Responses were evaluated according to modified Southwest Oncology Group criteria. Potential predictors of survival were analyzed with the Kaplan-Meier curve method (log-rank test) and multivariate analysis (P < 0.05). The response rates were 36.5% partial response, 17.6% minor response, 35.1% stable disease, and 10.8% progressive disease for the entire cohort; 54.5% partial response, 18.2% minor response, 18.2% stable disease, and 9.1% progressive disease for pancreatic NET; and 22.0% partial response, 17.1% minor response, 48.8% stable disease, and 12.2% progressive disease for nonpancreatic GEP NET. The median progression-free survival and overall survival were 26 mo (95% confidence interval, 18.3-33.7) and 55 mo (95% confidence interval, 48.8-61.2), respectively. Besides the Ki-67 index, a Karnofsky performance score of less than or equal to 70%, a hepatic tumor burden of greater than or equal to 25%, and a baseline plasma level of neuron-specific enolase of greater than 15 ng/mL independently predicted shorter overall survival (hazard ratio, 2.1-3.1). Patients with a Ki-67 index of greater than 10% still had median progression-free survival and overall survival of 19 and 34 mo, respectively. The results of this study demonstrated the favorable response and long-term outcome of patients with G1/G2 GEP NET after PRRT. Independent predictors of survival were the Ki-67 index, the patient's performance status (Karnofsky performance scale score), the tumor burden, and the baseline neuron-specific enolase level. Even patients with a Ki-67 index of greater than 10% seemed to benefit from PRRT, with a good response and a notable long-term outcome. We present the first evidence, to our knowledge, that even in patients with metastatic disease the distinction between G1 and G2-in particular, between G1 (Ki-67 index of 1%-2%) and low-range G2 (Ki-67 index of 3%-10%)-provides prognostic stratification.

Effect of bowel obstruction on stage IV colorectal cancer

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, with a high mortality rate, particularly among patients with advanced-stage disease complicated by bowel obstruction. The present study aimed to investigate the value of different surgical procedures and potential predictors of survival for patients with stage IV CRC, with or without bowel obstruction. Between August, 1994 and December, 2005, a total of 2,950 CRC patients were diagnosed and treated at our hospital. Among these, 381 patients had stage IV disease and were divided into two groups according to the presence (n=295) or absence (n=86) of bowel obstruction. The clinical data of all the patients with stage IV CRC were retrospectively analyzed and all the patients were followed up. Our results demonstrated statistically significant differences in gender, radical resection, histological type, ascites, tumor location, peritoneal and liver metastases between the obstruction and non-obstruction groups. We also observed that hepatic metastases and radical resection were factors associated with prognosis according to the univariate and multivariate analyses. Furthermore, the mean/median survival time was 49.4/21.6 and 37.2/17.1 months in the non-obstruction and obstruction groups, respectively. In conclusion, obstruction was not found to be an independent indicator of survival for patients with stage IV CRC, with patients in the obstruction group exhibiting a worse overall survival compared to those in the non-obstruction group, whereas active radical surgery significantly improved the prognosis of patients with stage IV CRC.

Baseline hypertension: New insight into the potential predictors of survival in patients with hepatocellular carcinoma

It is not clear whether baseline hypertension has a clinical impact in patients with hepatocellular carcinoma (HCC). The development of hypertension after anti-vascular endothelial growth factor (VEGF) therapy has been considered as a predictive biomarker of the response in various cancers, suggesting that hypertension-associated signaling pathways might be important [1–6]. In advanced HCC, although the inhibitor of vascular endothelial growth factor receptor (VEGFR) was associated with higher mean survival rate and radiological regression, it also significantly increased the incidence of hypertension as one of the complications [7–9].

VEGFR-2, CXCR-2 and PAR-1 germline polymorphisms as predictors of survival in pancreatic carcinoma

BackgroundHypoxic environment of pancreatic cancer (PC) implicates high vascular in-growth, which may be influenced by angiogenesis-related germline polymorphisms. Our purpose was to evaluate polymorphisms of vascular endothelial growth factor receptor 2 (VEGFR-2), CXC chemokine receptor 2 (CXCR-2), proteinase-activated receptor 1 (PAR-1) and endostatin (ES) as prognostic markers for disease-free (DFS) and overall survival (OS) in PC. Patients and methodsGenotyping of 173 patients, surgically treated for PC between 2004 and 2011, was carried out by TaqMan® genotyping assays or polymerase chain reaction. Chi-square test, Kaplan–Meier estimator and Cox regression hazard model were used to assess the prognostic value of selected polymorphisms. ResultsVEGFR-2 -906 T/T and PAR-1 -506 Del/Del genotypes predicted longer DFS (P = 0.003, P = 0.014) and OS (VEGFR-2 -906, P = 0.011). CXCR-2 +1208 T/T genotype was a negative predictor for DFS (P < 0.0001). Combined analysis for DFS and OS indicated that patients with the fewest number of favorable genotypes simultaneously present (VEGFR-2 -906 T/T, CXCR-2 +1208 C/T or C/C and PAR-1 -506 Del/Del) were at the highest risk for recurrence or death (P < 0.0001). ConclusionVEGFR-2 -906 C>T, CXCR-2 +1208 C>T and PAR-1 -506 Ins/Del polymorphisms are potential predictors for survival in PC.

Predictors of Survival among Pediatric and Adult Ependymoma Cases: A Study Using Surveillance, Epidemiology, and End Results Data from 1973 to 2007

Background: Despite previous research, prognostic factors for ependymoma remain relatively controversial. The purpose of our study was to examine demographic, clinical, and tumor attributes as potential predictors of survival using Surveillance, Epidemiology, and End Results (SEER) program data (1973–2007). Methods: All ependymoma (ICD-O-3 code 9391) and anaplastic ependymoma cases (ICD-O-3 code 9392) with complete data (n = 2,369 and n = 319, respectively) were included from SEER. Predictive Cox regression models were built separately among pediatric and adult cases. Recursive partitioning was used to corroborate results from regression models. Results: Among pediatric cases, tumor characteristics with a significantly increased mortality risk were anaplastic histology (vs. low grade, HR: 1.51, 95% CI: 1.04–2.19) and infratentorial tumor location (vs. spinal cord, HR: 3.86, 95% CI: 1.17–12.77). Among adults, supratentorial tumors were associated with higher mortality hazard (vs. spinal cord tumors) than infratentorial tumors (HR: 4.83, 95% CI: 3.49–6.68 and HR: 2.41, 95% CI: 1.79–3.25, respectively). Complete surgical resection of the tumor conferred the most protection among pediatric and adult patients. Conclusion: Our results indicate that treatment type and tumor characteristics are important prognostic factors in patients with ependymoma. However, there may be key differences between pediatric and adult cases regarding how these factors influence survival.

764 LYMPH NODE POSITIVE PROSTATE CANCER: WHICH FACTORS PREDICT SURVIVAL?

You have accessJournal of UrologyProstate Cancer: Advanced II1 Apr 2012764 LYMPH NODE POSITIVE PROSTATE CANCER: WHICH FACTORS PREDICT SURVIVAL? Michael Froehner, Rainer Koch, and Manfred Wirth Michael FroehnerMichael Froehner Dresden, Germany More articles by this author , Rainer KochRainer Koch Dresden, Germany More articles by this author , and Manfred WirthManfred Wirth Dresden, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.851AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The prognostic factors predicting survival in men with lymph node-positive prostate cancer are still poorly defined. We evaluated several tumor-related and host-related variables as potential predictors of survival in this population. METHODS 193 patients treated between 1993 and 2005 were studied. The median follow-up in the censored patients was 7.3 years. 94 % of patients received immediate hormonal therapy. Kaplan-Meier curves were calculated to evaluate overall survival rates. Competing risk analyses were used to determine prostate cancer-specific and competing mortality. Cox proportional hazard models were used to determine the independent significance of prognostic variables. RESULTS Age (70 years or older versus younger, hazard ratio (HR) 3.0), Gleason score (8-10 versus 7 or lower, HR 3.2) and the number of involved nodes (3 or more versus 1-2, HR 2.0) were identified as independent prognostic factors. The excess mortality in patients with adverse prognostic factors was attributable both to prostate cancer and to competing mortality. Comorbidity was associated with mortality in univariate but not in multivariate analysis. PSA was without any detectable prognostic significance. CONCLUSIONS A sizeable minority of narrowly one third of patients without additional adverse prognostic factors had an excellent long-term survival rate similar to that usually seen in patients with node-negative disease. Adverse comorbidity-related parameters seemed to shorten survival over-proportionally in patients with positive lymph nodes. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e312 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Michael Froehner Dresden, Germany More articles by this author Rainer Koch Dresden, Germany More articles by this author Manfred Wirth Dresden, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

P220 Transfer factor and arterial oxygen partial pressure are predictors of survival in hospital outpatients with COPD

IntroductionCOPD is a disorder characterised by high morbidity and mortality. Although several parameters have been used to predict survival among COPD patients, most of the information on the prognostic value...

Decompressive Craniectomy for Elderly Patients with Traumatic Brain Injury: It's Probably not Worth the While

Decompressive craniectomy (DC) has been regarded as an ultima ratio measure in the treatment of refractory intracranial hypertension after brain injury. Most discussion about its benefits is based on studies performed in patients who are <65 years of age. The aim of this study was to identify patients aged ≥66 years who underwent DC after traumatic brain injury (TBI), in order to assess patient outcome and to correlate the values of potential predictors of survival on prognosis. From January 2002 to December 2009, 44 patients aged ≥66 underwent DC (follow-up, 12-102 months). Potential predictors of outcome were analyzed, including age, post-resuscitation Glasgow Coma Scale (GCS) score, presence of mass lesion, Simplified Acute Physiology Score (SAPS) II, Injury Severity Score (ISS), and timing of surgical decompression. Mortality was 48% at discharge from the intensive care unit (ICU), 57% at hospital discharge, and 77% at 1-year follow-up and at last follow-up. A bad outcome Glasgow Outcome Scale Dead-Vegetative State-Severely Disabled (GOS D-VS-SD) was observed in 36/44 patients both at hospital discharge and at 1-year follow-up. Mean SAPS II was 45.2 for patients who survived and 57.3 for patients who had died (p=0.0022). Patients who survived had a higher mean post-resuscitation GCS score (p=0.02). Logistical regression analysis indicated post-resuscitation GCS score as the only independent predictive factor for outcome. None of the 22 patients with a post-resuscitation GCS score of 3-5 had a good outcome, 2/10 (20%) patients with a post-resuscitation GCS score of 6-8 and 6/12 patients (50%) with a post-resuscitation GCS score ≥9 had a good outcome.

Pathologic findings and clinical outcome in patients undergoing retroperitoneal lymphadenectomy after multiple chemorherapy regimens for metastatic nonseminomatous testicular tumors

We reviewed our experience with retroperitoneal lymphadenectomy (RPLA) after multiple cisplatin-based chemotherapy regimens in nonseminomatous testicular tumors (NSTT) patients and specifically evaluated clinicopathologic and treatment trend in addition to potential predictors of survival. Fort-one patients with NSTT underwent their RPLA between 1982 and 2005 after ≥ 2 regimens of chemotherapy. Thirteen patients (32%) necessitate redo- RPLA, combined with nephrectomy in 6 patients. 13 extra-RP (ERP) resections were performed in 11 patients (27%), including pulmonary (7), neck (4) and liver (2) sites. Thirty patients (73%) are rendered free of disease and 26 (63%) obtained serologic remission. Nine patients who relapse, necessitated new salvage chemotherapy+surgery (3 teratoma, 6 vital carcinoma [VC]). Four of 9 relapsing patients (44%) are currently free of disease with redo- RPLA. Alive, free of disease are 19 pts (46%) at median follow-up of 131 months. Study of RP pathology demonstrated the presence of fibrosis in 15%, teratoma in 39% and VC in 46%, with survival in 67%, 56% and 32%, respectively. Different histology occurred in 38% at redo-RPLA and in 64% at ERP resection in comparison to previous RP pathology. Univariate analysis of clinicopathologic parameters associated with VC at RPLA included RP masses ≥ 5 cm (p<0.05), elevated AFP (p<0.001) or HCG (p<0.05) and ERP resection (p<0.04). On univariate analysis survival was worse in patients with RP masses ≥ 5 cm (p<0.04), elevated AFP (p<0.05) or HCG (p<0.007), ERP resection (p<0.01) and VC (p<0.004). On multivariable analysis, a RP masses ≥ 5 cm (p<0.03) and VC (p<0.005) predicted a worse prognosis. Our data support the continued use of salvage RPLA in three separated groups of patients: 1. Patients who achieved a complete response (CR) to 2nd -line chemotherapy and have no radiologic evidence of disease should undergo RPLA; 2. Patients who achieved a partial response (PR) to chemotherapy should undergo RPLA with ERP surgery, as indicated; 3. Highly selected group of patients with residual masses and elevated serum tumor markers (STM), particularly AFP, after chemotherapy may be candidate for surgery.

Survival among patients with primary central nervous system lymphoma, 1973–2004

Primary central nervous system lymphoma (PCNSL) is a rare non-Hodgkin's lymphoma that occurs in immunocompetent and human immunodeficiency virus (HIV) patients. Despite treatment advances, previous reports have produced conflicting information about survival trends over time. Using the Surveillance, Epidemiology, and End Results (SEER) data, 2,557 patients diagnosed with PCNSL between 1973 and 2004 were identified and classified by HIV status. Potential predictors of survival were evaluated using log-rank tests. Hazard ratios and 95% confidence intervals (CIs) were computed using a Cox proportional hazards regression model. The cohort included 1,732 (67.7%) HIV-negative patients and 825 (32.3%) HIV-positive patients. Median overall survival was 12 months (95% CI 10, 13) among HIV-negative patients. In this group, median survival increased over time, from 7.5 months (95% CI 6, 14) for patients diagnosed in the 1970s, to 14 months (95% CI 11, 20) for patients diagnosed in the 2000s. Independent predictors of mortality included older age (hazard ratio [HR] 1.03 [95% CI 1.02, 1.03]), earlier year of diagnosis (HR 0.98 [95% CI 0.98, 0.99]), male sex (HR 1.20 [95% CI 1.08, 1.34), married status (HR 0.70 [95% CI 0.63, 0.78]), and receipt of radiation therapy (HR 0.69 [95% CI 0.61, 0.77]). HIV positivity was a powerful adverse prognostic factor in the overall cohort (HR 4.55 [95% CI 4.01, 5.16]). Despite treatment advances, survival among PCNSL patients in the United States remains poor. However, in the subset of PCNSL patients who are HIV-negative, survival has improved over time.

Sentinel Node Positive Melanoma Patients: Prediction and Prognostic Significance of Nonsentinel Node Metastases and Development of a Survival Tree Model

Completion lymph node dissection (CLND) following positive sentinel node biopsy (SNB) for melanoma detects additional nonsentinel node (NSN) metastases in approximately 20% of cases. This study aimed to establish whether NSN status can be predicted, to determine its effect on survival, and to develop survival tree models for the sentinel node (SN) positive population. Sydney Melanoma Unit (SMU) patients with at least 1 positive SN, meeting inclusion criteria and treated between October 1992 and June 2005, were identified from the Unit database. Survival characteristics, potential predictors of survival, and NSN status were assessed using the Kaplan-Meier method, Cox regression model, and logistic regression analyses, respectively. Classification tree analysis was performed to identify groups with distinctly different survival characteristics. A total of 323 SN-positive melanoma patients met the inclusion criteria. On multivariate analysis, age, gender, primary tumor thickness, mitotic rate, number of positive NSNs, or total number of positive nodes were statistically significant predictors of survival. NSN metastasis, found at CLND in 19% of patients, was only predicted to a statistically significant degree by ulceration. Multivariate analyses demonstrated that survival was more closely related to number of positive NSNs than total number of positive nodes. Classification tree analysis revealed 4 prognostically distinct survival groups. Patients with NSN metastases could not be reliably identified prior to CLND. Prognosis following CLND was more closely related to number of positive NSNs than total number of positive nodes. Classification tree analysis defined distinctly different survival groups more accurately than use of single-factor analysis.

S52 Pathologic findings and clinical outcome of patients undergoing retroperitoneal lymphadenectomy after multiple chemotherapy regimens for metastatic nonseminomatous testicular tumors

We reviewed our experience with retroperitoneal lymphadenectomy (rPLa) after multiple cisplatin-based chemotherapy regimens in nonseminomatous testicular tumors (NsTT) patients and specifically evaluated clinicopathologic and treatment trend in addition to potential predictors of survival. Fort-one patients with NsTT underwent their rPLa between 1982 and 2005 after ≥ 2 regimens of chemotherapy. Thirteen patients (32%) necessitate redo-rPLa, combined with nephrectomy in 6 patients. 13 extra-rP (ErP) resections were performed in 11 patients (27%), including pulmonary (7), neck (4) and liver (2) sites. Thirty patients (73%) are rendered free of disease and 26 (63%) obtained serologic remission. Nine patients who relapse, necessitated new salvage chemotherapy+surgery (3 teratoma, 6 vital carcinoma [VC]). Four of 9 relapsing patients (44%) are currently free of disease with redorPLa. alive, free of disease are 19 pts (46%) at median follow-up of 131 months. study of rP pathology demonstrated the presence of fibrosis in 15%, teratoma in 39% and VC in 46%, with survival in 67%, 56% and 32%, respectively. different histology occurred in 38% at redo-rPLa and in 64% at ErP resection in comparison to previous rP pathology. Univariate analysis of clinicopathologic parameters associated with VC at rPLa included rP masses ≥ 5 cm (p<0.05), elevated aFP (p<0.001) or HCG (p<0.05) and ErP resection (p<0.04). On univariate analysis survival was worse in patients with rP masses ≥ 5 cm (p<0.04), elevated aFP (p<0.05) or HCG (p<0.007), ErP resection (p<0.01) and VC (p<0.004). On multivariable analysis, a rP masses ≥ 5 cm (p<0.03) and VC (p<0.005) predicted a worse Patoloski nalaz i klinicki tok kod pacijenata sa metastazama neseminomskih testikularnih tumora kod kojih je primenjena retroperitonealna limfadenektomija posle multiplih hemoterapija Đordje M. argirovic1,3, aleksandar Đ. argirovic2 1Uroloska klinika, Klinicki Centar srbije “, Beograd 2Uroloska služba, Klinicko Bolnicki Centar Zemun, Beograd 3Poliklinika “argirovic, Beograd

Putative functional polymorphisms of MMP9 predict survival of NSCLC in a Chinese population

Matrix metalloproteinases (MMPs) play a crucial role in cancer progression and their over-expression is often associated with unfavorable survival of non-small cell lung cancer (NSCLC). Because genetic variants can alter expression level or biological activity of MMPs, we hypothesized that potentially functional single nucleotide polymorphisms (SNPs) in key MMP genes may be associated with the survival of NSCLC patients. We selected and genotyped 14 putative functional SNPs in six MMP genes (MMP1, MMP2, MMP3, MMP7, MMP9 and MMP12) using PCR-RFLP methods in 561 NSCLC patients. Kaplan-Meier method with the log-rank test and Cox proportional hazard models were used for the survival analyses. The C-1562T, Arg279Gln and Arg668Gln polymorphisms in MMP9 were significantly associated with survival of patients with NSCLC (log-rank p values = 0.032, 0.038 and 0.036, respectively). The C-1562T and Arg668Gln loci were in complete linkage disequilibrium (r(2) = 1). Patients carrying the 668Gln allele had improved survival with a median survival time (MST) of 51.6 months, compared with 21.8 months for those with the 668Arg/Arg genotype (log-rank p = 0.010). In contrast, the 279Gln/Gln genotype was associated with a significantly shortened MST (17.3 months, log-rank p = 0.030) in the recessive model. In the final multivariate Cox regression model, 279Gln/Gln was identified as an independent prognostic factor with an adjusted hazard ratio of 1.60 (95% confidence interval 1.07-2.41). The MMP9 Arg279Gln and Arg668Gln SNPs are potential predictors of survival in NSCLC patients.

The DNA repair proteins BRCA1 and ERCC1 as predictive markers in sporadic ovarian cancer

This study compares Breast Cancer 1 (BRCA1) and excision repair cross complementation group 1 (ERCC1) expression as predictive markers and evaluates the in vitro enhancement of platinum sensitivity using targeted agents in sporadic ovarian cancer (OC). A retrospective study was performed of advanced stage OC patients receiving platinum-based chemotherapy. BRCA1 and ERCC1 mRNA expression was determined from frozen tissue of 51 patients. Median overall survival (OS) was longer for patients with lower BRCA1 vs. higher BRCA1 (46 vs.33 months, p = 0.03). High BRCA1 was predictive of poorer OS specifically in patients with residual disease (RD) <2 cm (p = 0.03). There was a non-significant association for patients with lower ERCC1 and RD <2 cm in favor of improved OS and time to progression. Patients who expressed higher levels of both BRCA1 and ERCC1 mRNA had a shorter OS compared to patients with lower levels of either or both transcript (33 vs.46 months, p = 0.04). When Cox proportional modeling was used by representing BRCA1 and ERCC1 mRNA expression as a continuous variable, both emerge as potential predictors of survival. OC cell lines were exposed to chemotherapy in combination with DNA repair pathway inhibitors and cell viability was assessed. In vitro histone deacetylase (HDAC) inhibition increased the sensitivity of A2780s/cp cells to cisplatin and carboplatin but not to taxol, coincident with a significant decrease in BRCA1 and ERCC1 expression, suggesting that this compound directly targets DNA repair. In summary, this study shows that low BRCA1 and ERCC1 expression correlate with improved survival in advanced OC and HDAC inhibition induces synergistic cytotoxicity with platinum in vitro.

MicroRNA-21 is Overexpressed in Pancreatic Cancer and a Potential Predictor of Survival

BackgroundMicroRNAs are small (18–22 nucleotides) noncoding RNAs involved in posttranscriptional modification of many target genes. One of these, microRNA-21 (miR-21), has been shown to play a role in multiple hematologic and solid organ malignancies. We sought to determine the expression pattern of miR-21 in pancreatic cancers and its impact on clinicopathologic characteristics. MethodsEighty resected pancreatic cancer specimens were microdissected and tissue microarrays (TMA) created in duplicate. TMAs were also created for benign pancreas (N = 12) and chronic pancreatitis (N = 45). In situ hybridization (ISH) was undertaken utilizing locked nucleic acid probes for miR-21. RNA U6 and scrambled RNA served as positive and negative control, respectively. ISH was scored as 0 (absent), 1+ (faint/focal expression), or 2+ (strong expression). Kaplan–Meier survival curves were constructed and compared by log-rank analysis. ResultsMiR-21 expression was demonstrated in 63 (79%) pancreatic cancers (1+ in 49, 2+ in 14) compared to one of 12 (8%, p < 0.0001) benign pancreas and 12/45 (27%, p < 0.0001) chronic pancreatitis. None of the benign tissues demonstrated strong miR-21 expression. Although miR-21 expression did not correlate with tumor size, differentiation, nodal status, or T stage, strong miR-21 expression was predictive of poorer outcome compared to absent or faint/focal miR-21 expression in patients with node-negative disease (median 27.7 months vs. 15.2, p = 0.037). Nodal status was also predictive of survival (p = 0.029). ConclusionsMicroRNA-21 is significantly overexpressed in pancreatic cancers as detected by in situ hybridization. Its strong expression predicts limited survival in patients with node-negative disease and may be an important biologic marker for outcome.

The Transfusion Iron Overload Score Is a Potential Predictor of Survival in Stem Cell Transplant Patients.

Iron overload at the time of bone marrow transplantation has recently been associated with increased mortality. The mechanism by which iron overload negatively impacts survival is unclear. In an effort to better define iron overload and its potential role in the transplant setting, we examined 78 consecutive patients at risk for transfusion-related iron overload (AML, ALL, MDS, and aplastic anemia) undergoing either autologous or allogeneic stem cell transplant at our institution between 1999 and 2004. To estimate transfusion-related iron overload, we devised a novel scoring system based on routinely available laboratory variables obtained prior to transplant. In our scoring system, a single point was awarded for each of the following:1.number of red cell units transfused prior to transplantation > 25;2.serum ferritin > 1000 ng/ml; and3.a semi-quantitative bone marrow iron stain of 6+.The Transfusion Iron Overload Score (range of 0 to 3) predicted for overall survival in our patient sample (Fig. 1, p = 0.0003 by Kaplan-Meier log rank trend) and was more powerful than using serum ferritin alone (p = 0.02). The calculated score retained its significant association with overall survival while controlling for traditional risk factors (age, sex, diagnosis, transplant type, donor relation, and remission status), inflammation (c-reactive protein), and measures of organ damage (transaminases, total bilirubin, INR, and cardiac ejection fraction) (p = 0.04 by Cox proportional-hazards regression). The 27 patients (35%) with a high score (≥ 2) had a dramatically lower median survival of 5.0 months compared to 29.3 months in those with an iron score of less than two (unadjusted hazard ratio of 2.5; 95% CI of 1.6 to 6.3). The observed mortality seen in those with a high score was primarily attributable to treatment-related mortality (p = 0.018) rather than disease-related mortality (p = 0.48). This finding likely accounts for the significant survival impact of iron overload seen in the allogeneic (p = 0.006) but not the autologous (p = 0.48) subgroup. In conclusion, the Transfusion Iron Overload Score served as a strong independent predictor of survival in our stem cell transplant population, identifying patients at significant risk for early treatment-related mortality. Our results lend further support to the notion that iron overload is detrimental in the transplant setting, and for the first time suggest that transfusion-related iron overload increases mortality via a mechanism independent of pre-existing inflammation and end-organ dysfunction. [Display omitted]

The prognostic factors of stage IV colorectal cancer and assessment of proper treatment according to the patient’s status

Approximately 20% of patients with colorectal cancer are initially diagnosed with stage IV. The majority has non-curative metastases, and their chances of survival are pitiful. This study evaluated the prognostic factors of survival and the access to the effective treatment in accordance with patients. We retrospectively analyzed 503 patients for demographics, tumor characteristics, the treatment modality, and the survival outcome. Curative operation was performed in 127 patients and palliative operation in 376 patients. For the curative operation group, the 5-year survival rate was 34.5%, and the prognostic factors of survival and recurrence were male gender (p = 0.003, 0.009), pathologic N stage (p < 0.001, p = 0.002), and perineural invasion (p = 0.003, p = 0.026), respectively. For the non-curative operation group, the 5-year survival rate was 0%, and the median survival duration was 16.5 months. The potential predictors of survival for the palliative operation group were carcinoembryonic antigen level (p = 0.013), differentiation of tumor (p = 0.011), resection of primary tumor (p < 0.001), and chemotherapy (p < 0.001). But for the 131 patients with asymptomatic incurable disease, only chemotherapy was related to survival (p < 0.001). The potential predictors of survival for curative stage IV colorectal cancer were male gender, pathologic N stage, and perineural invasion. Resection of the primary tumor and chemotherapy showed benefit for the incurable patients. But for the asymptomatic incurable patients, only chemotherapy prolonged the survival.

Brain Metastases From Breast Carcinoma: Validation of the Radiation Therapy Oncology Group Recursive Partitioning Analysis Classification and Proposition of a New Prognostic Score

To validate the Radiation Therapy Oncology Group Recursive Partitioning Analysis (RTOG RPA) classification and determine independent prognostic factors, to create a simple and specific prognostic score for patients with brain metastases (BM) from breast carcinoma treated with whole-brain radiotherapy (WBRT). From January 1998 through December 2003, 132 patients with BM from breast carcinoma were treated with WBRT. We analyzed several potential predictors of survival after WBRT: age, Karnofsky performance status, RTOG-RPA class, number of BM, presence and site of other systemic metastases, interval between primary tumor and BM, tumor hormone receptor (HR) status, lymphocyte count, and HER-2 overexpression. A total of 117 patients received exclusive WBRT and were analyzed. Median survival with BM was 5 months. One-year and 2-year survival rates were 27.6% (95% confidence interval [CI] 19.9-36.8%) and 12% (95% CI 6.5-21.2%), respectively. In multivariate analysis, RTOG RPA Class III, lymphopenia (< or =0.7 x 10(9)/L) and HR negative status were independent prognostic factors for poor survival. We constructed a three-factor prognostic scoring system that predicts 6-month and 1-year rates of overall survival in the range of 76.1-29.5% (p = 0.00033) and 60.9-15.9% (p = 0.0011), respectively, with median survival of 15 months, 5 months, or 3 months for patients with none, one, or more than one adverse prognostic factor(s), respectively. This study confirms the prognostic value of the RTOG RPA classification, lymphopenia, and tumor HR status, which can be used to form a prognostic score for patients with BM from breast carcinoma.

Using Geographic Information Systems to Evaluate Cardiac Arrest Survival

Objective. To evaluate cardiac arrest survival using geographical information systems (GIS) methodology. Methods. Patient data were obtained from a fire district Utstein-style adult cardiac arrest registry that also included address data. All incident locations were geocoded andfire station first-due areas were mapped by using the new computer-aided dispatch geographic data. Retrospective assignment of first-due versus second-due fire response unit was done by using a GIS “point-in-polygon” algorithm Survival to hospital admission was the primary outcome measure for incidents responded to by first-due versus second-due apparatus controlling for other potential predictors of survival using logistic regression. Cluster analysis was also performed to evaluate potential areas of high or low rates of survival. Results. There were 461 eligible patients with an average age of 67 ± 17 years, 63% were male, 53% had a witnessed arrest, bystander cardiopulmonary resuscitation was performed in 38%, bystander automatic external defibrillator (AED) Page: 1 was used in 0.01%, ventricular fibrillation or ventricular tachycardia were the presenting rhythms in 44%, the average response time was 5.5 ± 2.1 minutes, andsurvival to hospital admission was 17%. There was no significant difference in response time between survivors (4.97 minutes) andnon-survivors (5.52 minutes), (difference 0.55 minutes, 95%CI −0.08 to 1.18 min). The number of cardiac arrest calls varied from 1 to 49 for each station andthe rate of second-due response varied from 0 to 19%. There was a nonsignificant association of survival to hospital admission for the first-due area cohort: odds ratio 0.70, 95% CI 0.38–1.29. Conclusion GIS is a new methodology for analyzing EMS incident data. It adds a spatial component of analysis to traditional statistical techniques. No spatial difference was found on patient survival in this analysis. Key words: cardiac arrest; emergency medical services; geographical information systems.

Epidermal growth factor (EGF) A61G polymorphism and EGF gene expression in normal colon tissue from patients with colorectal cancer

Introduction. EGF/EGFR interactions are important mechanisms behind colorectal tumour development and growth. Recently a single nucleotide polymorphism in the EGF gene has been identified (EGF A61G). It may be a potential predictor for survival of patients receiving EGFR-inhibitor cetuximab treatment, but the clinical importance and the functional influence on EGF gene expression levels in colorectal cancer (CRC) patients have not yet been further assessed. The aim of the present study was to investigate the relationship between EGF A61G genotype and EGF gene expression levels in colorectal adenocarcinomas and normal colon tissue. Material and methods. Eighty-one CRC patients were included in the study. Tissue samples from normal colon, adenocacinomas and corresponding blood samples were analysed by real-time PCR for EGF gene expression and EGF A61G genotype, respectively. Results. Thirty-three percent were AA, 48% and 19% A/G and G/G respectively. We found a significantly lower median age in the A/A group compared to the G/G group, suggesting a later time of diagnosis in the G/G patients. There was a significant difference between the median EGF gene expression among the three genotypes in normal colon (p < 0.001) but not in adenocarcinomas. Furthermore, the median EGF gene expression was lower in CRC tissue than in normal colon samples, (0.13 (range 0.01–6.4) vs. 0.76, (range 0.013–5.55)). Conclusion. We suggest that EGF A61G genotype has a functional influence on EGF gene expression in normal colon in CRC patients. The clinical implications warrant further investigations in prospective trials.