Favorable Prognostic Factor For Survival Research Articles

Relapse of Lymphoma after Allogeneic Hematopoietic Cell Transplantation: Management Strategies and Outcome

The outcome and management of relapsed lymphoma after allogeneic hematopoietic cell transplantation (HCT) is difficult. Therapeutic options may include donor lymphocyte infusion (DLI), reduction of immunosuppression (RIS), chemotherapy, radiation, immunotherapy, second HCT, and experimental treatments, but reported data contrasting the response and efficacy of these salvage treatments are limited. We describe the treatments, response, prognosis, and long-term survival of 72 patients with relapse of lymphoma after allogeneic HCT. Between 1991 and 2007, 227 lymphoma patients underwent allogeneic HCT. Of these, 72 (32%) developed relapse/progression after their HCT at a median of 99 days (0-1898 days); 37 had early (<100 days) post-HCT relapse. Forty-four had non-Hodgkin lymphoma (7 mantle cell, 5 indolent, 15 diffuse large B cell, 4 Burkitt's, and 13 T/Natural Killer cell), and 28 patients had Hodgkin lymphoma. At the time of HCT, 62 patients were in remission (22 in complete [CR] and 40 in partial [PR]), 1 had stable whereas 9 had progressive disease. Seventeen cases received myeloablative and 55 received a reduced-intensity conditioning regimen. At relapse, most patients had generalized lymphadenopathy, extranodal organ involvement, and advanced disease. Five patients received no intervention for the post-HCT relapse. Immunosuppressive treatment was reduced or withdrawn as the first-line therapy in 58 patients (80.5%); 47 were treated using combinations of conventional chemotherapy (n = 22), rituximab (n = 27), interferon (IFN) (n = 1), DLI (n = 7), second HCT (n = 2), local radiation (n = 23), and other therapy (n = 6). Thirty-eight patients had an objective response (CR in 30, PR in 8), and 2 had stable disease (SD). At the post-HCT relapse, favorable prognostic factors for survival after HCT included good ECOG performance status (0-2), normal lactate dehydrogenase (LDH), early stage disease (stage I-III), isolated extranodal organ involvement, and later relapse (>100 days) post-HCT. Three-year survival after HCT was significantly better in late than early relapse (53%; 95% confidence interval [CI] [34%-69%] versus 36%, [20%-52%], P = .02). Of 72 relapsed patients, 29 (40%) survived at a median of 34 (3-148) months posttransplant. The most common cause of death was underlying lymphoma (79%). The overall prognosis of relapsed/progressive lymphoma after allogeneic HCT is disappointing, yet half of patients respond to withdrawal of immunosuppression and additional therapies. Novel treatments can control lymphoma with acceptable morbidity. Particularly for patients with later relapse, ongoing treatment after relapse can yield meaningful benefit and prolonged survival.

Characterization of CEBPA mutations and promoter hypermethylation in pediatric acute myeloid leukemia

Dysfunctioning of CCAAT/enhancer binding protein α (C/EBPα) in acute myeloid leukemia can be caused, amongst others, by mutations in the encoding gene (CEBPA) and by promoter hypermethylation. CEBPA-mutated acute myeloid leukemia is associated with a favorable outcome, but this may be restricted to the case of double mutations in CEBPA in adult acute myeloid leukemia. In pediatric acute myeloid leukemia, data on the impact of these mutations are limited to one series, and data on promoter hypermethylation are lacking. Our objective was to investigate the characteristics, gene expression profiles and prognostic impact of the different CEBPA aberrations in pediatric acute myeloid leukemia. We screened a large pediatric cohort (n=252) for CEBPA single and double mutations by direct sequencing, and for promoter hypermethylation by methylation-specific polymerase chain reaction. Furthermore, we determined the gene-expression profiles (Affymetrix HGU133 plus 2.0 arrays) of this cohort (n=237). Thirty-four mutations were identified in 20 out of the 252 cases (7.9%), including 14 double-mutant and 6 single-mutant cases. CEBPA double mutations conferred a significantly better 5-year overall survival compared with single mutations (79% versus 25%, respectively; P=0.04), and compared with CEBPA wild-type acute myeloid leukemia excluding core-binding factor cases (47%; P=0.07). Multivariate analysis confirmed that the double mutations were an independent favorable prognostic factor for survival (hazard ratio 0.23, P=0.04). The combination of screening for promoter hypermethylation and gene expression profiling identified five patients with silenced CEBPA, of whom four cases relapsed. All cases characteristically expressed T-lymphoid markers. Moreover, unsupervised clustering of gene expression profiles showed a clustering of CEBPA double-mutant and silenced cases, pointing towards a common hallmark of abrogated C/EBPα-functioning in these acute myeloid leukemias. We showed the independent favorable outcome of patients with CEBPA double-mutant acute myeloid leukemia in a large pediatric series. This molecular marker may, therefore, improve risk-group stratification in pediatric acute myeloid leukemia. For the first time, CEBPA-silenced cases are suggested to confer a poor outcome in pediatric acute myeloid leukemia, indicating that further investigation of this aberration is needed. Furthermore, clustering of gene expression profiles provided insight into the biological similarities and diversities of the different aberrations in CEBPA in pediatric acute myeloid leukemia.

Consequent and intensified relapse therapy improved survival in pediatric AML: results of relapse treatment in 379 patients of three consecutive AML-BFM trials

Relapse remains the major cause of treatment failure in pediatric acute myeloid leukemia (AML). We analyzed the clinical characteristics, treatment response to relapse treatment and overall survival (OS) of 379 children with AML relapse treated according to three consecutive frontline protocols of the AML-Berlin/Frankfurt/Muenster study group (AML-BFM-87/-93/-98). Of 313 treated patients with data on remission status, 198 children (63%) achieved a second complete remission (CR2). There were no significant differences in remission rates and OS for the intensive reinduction treatment schedules used. The 5-year OS rate was 23% for the total group and 29% for patients treated with curative intent. OS rates increased with study periods from 18 to 34% (P(log rank)=0.012), whereas the proportion of patients receiving only palliative treatment decreased from 23 to 11% (P(CMH)=0.005). Late relapse, no allogeneic stem cell transplantation (SCT) in CR1, age <10 years and favorable cytogenetics were independent favorable prognostic factors for survival. Achievement of CR2 was the most important prognostic factor (OS 44 vs 3%; P(log rank)<0.0001). Overall, one-third of children with relapsed AML can be cured today. SCT in CR2 is recommended for most patients, although its impact on CR2 is discussed.

Performance Status and Smoking Status Are Independent Favorable Prognostic Factors for Survival in Non-small Cell Lung Cancer: A Comprehensive Analysis of 26,957 Patients with NSCLC

Performance status (PS) is an important factor in determining survival outcome in non-small cell lung cancer (NSCLC) but is generally confounded by stage, age, gender, and smoking status. We investigated the prognostic significance of PS taking into account these important factors. Retrospective analysis of registry database of the National Hospital Study Group for Lung Cancer (NHSGLC) between 1990 and 2005. Univariate analysis was performed using Kaplan-Meier method. Multivariate analysis was performed using Cox proportional hazards model to identify independent prognostic factors. A total of 26,957 patients with NSCLC were analyzed of which 12,613 patients (46.8%) had World Health Organization (WHO) PS = 0, 8,137 patients were never smokers (30.2%), and most of them were females (72.7%). The majority of PS = 0 patients presented with stage I disease (56.9%). Patients with PS = 0 constituted the group with the highest proportion of never smokers (36.7%). There was a significant difference in the median overall survival (OS) between patients with PS = 0 and PS = 1 (51.5 months versus 15.4 months, respectively; p < 0.0001) and among patients with various PS within individual American Joint Committee on Cancer stage (all p values <0.0001). Never smokers had significantly improved median OS than ever smokers (30.0 months versus 19.0 months, respectively; p < 0.0001). Multivariate analysis demonstrated good PS, never smoker (versus ever smoker; hazard ratio = 0.935, 95% confidence interval: 0.884-0.990; p = 0.0205), early stage, female gender, squamous cell carcinoma histology, and treatment were all as independent favorable prognostic factors. PS and smoking status are independent prognostic factors for OS in NSCLC.

Hypoxia-Inducible Factor-1 α Expression Predicts Superior Survival in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP

PURPOSE Hypoxia-inducible factor (HIF) controls the expression of genes in response to hypoxia, as well as a wide range of other cellular processes. We previously showed constitutive stabilization of HIF-1alpha in the majority of patients with diffuse large B-cell lymphoma (DLBCL). To our knowledge, the prognostic significance of HIF in lymphoma has never been investigated. PATIENTS AND METHODS We studied the immunohistochemical protein expression of HIF-1alpha on tissue microarrays from 153 patients with DLBCL treated in sequential cohorts with cyclophosphamide, doxorubicin, oncovin, and prednisone (CHOP) or rituximab-CHOP (R-CHOP) from 1999 to 2002. Results were correlated with patient outcome. Results Median follow-up for all patients was 80 months. Among all patients, HIF-1alpha was expressed in 62% of germinal center and 59% of non-germinal center patients. With HIF-1alpha analyzed as a dependent variable, there were no survival differences in CHOP-treated patients. In the R-CHOP group, however, HIF-1alpha protein expression correlated with significantly improved progression-free survival (PFS) and overall survival (OS). Five-year PFS for HIF-1alpha-positive patients was 71% v 43% for HIF-1alpha-negative patients (P = .0187), whereas 5-year OS was 75% and 54%, respectively (P = .025). In multivariate analysis with International Prognostic Index criteria, HIF-1alpha remained a significant predictor for PFS (P = .026) and OS (P = .043). Compared with other biomarkers, HIF-1alpha correlated only with BCL6 (P = .004). In terms of gene expression, we found several common gene associations of HIF-1alpha and the stromal-1 signature with genes predominantly involved in regulation of the extracellular matrix (eg, BGN, COL1A2, COL5A1, and PLOD2). CONCLUSION The expression of HIF-1alpha protein is an important independent favorable prognostic factor for survival in patients with DLBCL treated with R-CHOP.

Low-grade oligodendroglioma: an indolent but incurable disease?

The authors reviewed their institutional experience with pure low-grade oligodendroglioma (LGO), correlating outcomes with several variables of possible prognostic values. Sixty-nine patients with WHO-classified LGOs were treated between 1992 and 2006 at the McGill University Health Center. Clinical, pathological, and radiological records were carefully reviewed. Demographic characteristics; the nature and duration of presenting symptoms; baseline neurological function; extent of resection; Karnofsky Performance Scale score; preoperative radiological findings including tumor size, location, and absence/presence of enhancement; and pathological data including chromosome arms 1p/19q codeletion and O-methylguanine-DNA methyltransferase promoter gene methylation status were all compiled. The timing and dose of radio- and/or chemotherapy, date of tumor progression, pathological finding at disease progression, treatment at time of disease progression, and status at the last follow-up were also recorded. The median follow-up period was 6.1 years (range 1.3-16.3 years). The majority (78%) of patients presented with seizures; contrast enhancement was initially seen in 16 patients (25%). All patients had undergone an initial surgical procedure: gross-total resection in 27%, partial resection in 59%, and biopsy only in the remaining 13%. Fifteen patients received adjuvant radiotherapy. Data on O-methylguanine-DNA methyltransferase promoter gene methylation status was available in 47 patients (68%) and in all but 1 patient for 1p/19q status. Survival at 5, 10, and 15 years was 83, 63, and 29%, respectively. Multivariate analysis showed that seizures at presentation and the absence of contrast enhancement were the only independent favorable prognostic factors for survival. The 5-, 10-, and 15-year progression-free survival rates were 46, 7.7, and 0%, respectively. This retrospective review confirms the indolent but progressively fatal nature of LGOs. Contrast enhancement was the most evident single prognostic factor. New treatment strategies are clearly needed in the management of this disease.

Valproic Acid at Therapeutic Plasma Levels May Increase 5-Azacytidine Efficacy in Higher Risk Myelodysplastic Syndromes

Epigenetic changes play a role and cooperate with genetic alterations in the pathogenesis of myelodysplastic syndromes (MDS). We conducted a phase II multicenter study on the combination of the DNA-methyltransferase inhibitor 5-azacytidine (5-AZA) and the histone deacetylase inhibitor valproic acid (VPA) in patients with higher risk MDS. We enrolled 62 patients with MDS (refractory anemia with excess blasts, 39 patients; refractory anemia with excess blasts in transformation, 19 patients; and chronic myelomanocytic leukemia (CMML), 4 patients) and an International Prognostic Scoring System (IPSS) rating of Intermediate-2 (42 patients) or high (20 patients). VPA was given to reach a plasma concentration of >50 microg/mL, then 5-AZA was added s.c. at 75 mg/m(2) for 7 days in eight monthly cycles. The median overall survival was 14.4 months. At a median follow-up of 12 months (range, 0.7-21.0), the disease progressed in 20 patients, with 21% cumulative incidence of progression. Of 26 patients who completed eight cycles, 30.7% obtained complete or partial remission, 15.4% had a major hematologic improvement, whereas 38.5% showed stable disease. Drug-related toxicity was mild. Favorable prognostic factors for survival were IPSS Intermediate-2 and plasma VPA of > or =50 microg/mL (log rank = 0.013 and 0.007, respectively). Analysis of polymorphisms important for the metabolism of the drugs used in the trial showed that carriers of the CYP2C19*2 variant of cytochrome P450 required higher VPA doses to achieve the target VPA plasma concentration of 50 microg/mL on day 1 of 5-AZA treatment (P = 0.0021). Our data show that the 5-AZA/VPA combination is active and safe in patients with MDS with a poor prognosis. Achievement of VPA therapeutic levels may indeed increase 5-AZA efficacy.

Survival and prognostic factors in small cell lung cancer

The purposes of this study were to evaluate the treatment outcome of patients with small cell lung cancer (SCLC), focusing on the prognostic factors for response to therapy and overall survival. A retrospective analysis was performed on 116 consecutive patients with SCLC diagnosed from January 1997 to December 2005. Collected data included demographic information, pretreatment clinical assessment, treatment regimen, and outcome information. Prognostic factors were analyzed by log-rank test and Cox regression model. Results showed that performance status (PS) 0-1, limited disease, normal serum carcinoembryonic antigen (CEA), and vascular endothelial growth factor (VEGF) level were associated with improved response rate. The univariate analysis showed that sex, disease extent, PS, serum CEA, and VEGF level significantly influenced overall survival. In multivariate analysis, disease extent, PS, serum CEA, and VEGF level were identified as independent prognostic factors. In addition, prophylactic cranial irradiation (PCI) and number of metastatic sites were independent prognostic factors in limited disease and extensive disease, respectively. We concluded that disease extent, PS, serum CEA, and VEGF level are strong predictors of both response and survival. Female sex was a favorable prognostic factor for survival. Moreover, the prognostic factors for limited disease were good PS, normal serum CEA and VEGF level, and PCI, the prognostic factors for extensive disease were good PS, one metastatic site, normal serum CEA, and VEGF level. The identification of prognostic factors may be useful for the better evaluation of treatment outcome in clinical trials and the use of a targeted and specific treatment.

Prognostic Significance of the Non–Size-Based AJCC T2 Descriptors: Visceral Pleura Invasion, Hilar Atelectasis, or Obstructive Pneumonitis in Stage IB Non-small Cell Lung Cancer Is Dependent on Tumor Size

<h3>Background</h3> The T2 descriptor for staging non-small cell lung cancer (NSCLC) contains several non–size-based criteria. It remains unknown whether the prognostic significance of these non–size-based criteria is dependent on tumor size. <h3>Methods</h3> A total of 10,545 patients with stage IB NSCLC from the California Cancer Registry between 1989 to 2003 were categorized into the following three nonoverlapping criteria: (1) tumor size (T2S); (2) visceral pleura invasion, hilar atelectasis, or obstructive pneumonitis (T2P); and (3) main bronchus involvement ≥ 2 cm from the carina (T2C). Univariate survival analyses were performed using the Kaplan-Meier method. Multivariate survival analyses were performed using Cox proportional hazards ratios. <h3>Results</h3> A total of 51.1% of patients with stage IB NSCLC were staged by T2S, 43.2% by T2P, and 5.7% by T2C; 2,224 stage IB patients (total, 21.1%; 18.9% T2P + 2.2% T2C) had tumors ≤ 3 cm in size. The 5-year survival rate and the median survival time of these stage IB patients with tumors ≤ 3 cm in size were as follows: T2P, 51.2% and 64 months, respectively; T2C, 49.0% and 58 months, respectively. These values were similar to the 53.2% 5-year survival rate and 67-month median survival time for patients with stage IA NSCLC (p = 0.40). Cox proportional hazards model revealed T2P of > 3 cm was a poor prognostic factor for survival (vs T2S; hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.08 to 1.24). Conversely, T2P ≤ 3 cm was a favorable prognostic factor for survival (vs T2S; HR, 0.89; 95% CI, 0.82 to 0.96). T2C was not an independent prognostic factor for survival. <h3>Conclusions</h3> Prognostic significance of the non–size-based T2 descriptor T2P is dependent on tumor size.

Efficacy vs. effectiveness — docetaxel and prednisone in hormone refractory prostate cancer

To assess the clinical effectiveness of docetaxel and prednisone in a clinical setting and to compare the results to those seen in the pivotal clinical trial. To assess the impact of various factors on the prognosis of patients treated with docetaxel. Retrospective chart review. The primary outcome measured was survival. Survival data was analyzed through the Kaplan-Meier methodology. A multivariate analysis of prognostic variables was also conducted. Public cancer centers within the Canadian province of Alberta. Hormone refractory, metastatic prostate cancer patients initiated on docetaxel chemotherapy between September 2004 and February 2007 within the Alberta Cancer Board. Main Outcome Measured. The primary outcome measured was median survival. Among 161 patients eligible for review, median survival was 17.22 months. Chemotherapy received after docetaxel was determined to be a significant favorable prognostic factor for survival (p<0.0001). In a clinical setting, docetaxel and prednisone did not perform as well in terms of median survival, as it was shown to in prior clinical trials (17.22 vs. 18.9 months). Further investigation into the impact of docetaxel and prednisone on quality of life in clinical practice, would complement the findings of this study.

Treatment of recurrent glioblastoma: can local delivery of mitoxantrone improve survival?

In this study, the records of 276 adult patients with recurrent glioblastoma (GBM) treated at recurrence at our institution between 2004 and 2006 were reviewed for progression-free survival (PFS), overall survival (OS), and toxicity. At recurrence, all patients underwent systemic treatment with temozolomide (200 mg/sqm on days 1-5 every 28 days) until tumor progression. Patients, whose tumor was judged resectable without risk of adjunctive neurological deficit, underwent a second surgery with or without positioning of a Rickam/Ommaya reservoir. The reservoir was used for locoregional chemotherapy with mitoxantrone. Two hundred seventy-six rGBL patients (pts) were divided into three subgroups: A 161 pts treated only with temozolomide, B 50 pts re-operated-on +temozolomide, and C 65 pts re-operated on + temozolomide + locoregional CHT. For group A, the 6 month PFS and 6 month survival (ST) were 39.3 and 43%, respectively, with a median survival time (mST) of 5 months (range 4-6) and 25% of pts alive at 9 months. For group B, the 6 month PFS and 6 month survivors were 64 and 74.1%, respectively, with a mST of 8 months (range 6-10) and 25% of pts alive at 12 months. For group C, the 6 month PFS and 6 month survivors were 70.7 and 87.7%, respectively, with a mST of 11 months (range 9-13) and 25% of pts alive at 18 months (A vs. B vs. C, log-rank P < 0.001) (B vs. C, P = 0.041) (A vs. B P = 0.009). Cox proportional hazard model was used to obtain Hazard Ratio (HR) for type of treatment corrected by age and time (in months) between diagnosis and first recurrence: second tumor debulking was statistically effective for survival, reducing by 36% the risk of death (HR = 0.64; 0.46-0.89), but the most significant favorable prognostic factor for survival was the local delivery of mitoxantrone which reduced the risk of death to 50% (HR = 0.50; 0.38-0.68).

P3-208: Clinical features and treatment outcome of bronchioloalveolar carcinoma defined by who classification

Bronchioloalveolar carcinoma (BAC) is defined as an adenocarcinoma with pure bronchioloalveolar growth pattern and no evidence of stromal, vascular or pleural invasion by 1999 WHO classification. Although BAC has unique clinical and radiological presentations, BAC has been defined inconsistently in various series. We analyzed the clinical features, treatment outcome and prognostic factors of 141 BAC patients in a single institution. From September 1994 to December 2004, a total of 5,063 patients were diagnosed of non-small lung cancer (NSCLC) at Samsung Medical Center in Korea. Of 5,063 patients, 141 patients (2.8% of NSCLC, 5.2% of adenocarcinoma) were diagnosed of BAC according to the 1999 WHO criteria. The clinical data including radiological features, treatment modalities, relapse and vital status were retrospectively obtained. Among the 141 patients, 100 patients (71%) underwent surgical resection with curative intent. The male to female ratio was 0.85:1 and the median age was 62 years (range, 29 - 83). Only 29% of the patients were current or ex-smokers. Most patients (61%) had clinicopatholgic stage I, 5% stage II, 8% stage III, and 26% of the patients presented with stage IV disease. The most common initial radiological presentation was solitary nodule (63%) followed by multiple nodules in both lungs (18%), infiltrating or pneumonic mass (9%), multiple nodules in the same lung (6%), and a cavitary mass (4%). The most frequent location of the tumor was the right upper lobe (28%) followed by the right lower lobe (17%), the left lower lobe (16%), the left upper lobe (9%), and the right middle lobe (6%). The estimated 5-year overall survival rate of the 100 patients who underwent surgical resection was 71.4 %, and the median survival has not been reached yet. Among the resected patients, 24 patients de-veloped relapse mostly in the lung (19 patients, 78%). The median survival was 6.9 months for the 39 patients without surgical resection. At the multivariate analysis, initial radiological presentation with solitary nodule and curative resection were favorable prognostic factors for survival. Pure BAC is uncommon lung adenocarcinoma in Korea. Patients with localized, resectable disease and initial radiological finding of solitary nodule have a significantly better survival.

Spotlight

Chan et al., pp. 474–485 For women with breast cancer the odds of survival dramatically change when the tumor progresses from in situ carcinoma to infiltrative cancer. While the noninvasive form causes death in 1% or less, 28–50% of patients with invasive cancer die. The transition from in situ to infiltrative tumor is therefore a key step in breast cancer development. However, current models for studying this step are limited. Chan and colleagues used a rat model, which recapitulated phenotypic changes observed in the in situ- to-invasive transition. They treated rats with N-methyl-N-nitrosourea (NMU), a widely used carcinogen to experimentally induce mammary tumors. Although NMU-induced tumors are typically low-grade in situ carcinomas, they can develop the capacity for invasion following serial transplantation. These scientists found that the majority of transplanted lineages maintained a ductal morphology and biomarker expression, characteristics of noninvasive tumors. In addition, two histological types of invasive tumors were observed: a mesenchymal lineage that resembled human breast carcinosarcomas and one series of transplants that resembled the recently recognized “basal-like” human breast cancer subtype. When the authors compared noninvasive and highly invasive tumors by gene-expression profiling they identified a total of 136 genes that were upregulated in highly invasive tumors. In addition, they identified 83 genes that were downregulated. Both lists included genes involved in cell adhesion, the extracellular matrix, cell cycle progression and signal transduction. The authors propose that a “reprogramming” in gene expression occurs at the in situ-to-invasive transition, leading to a gradual change in the state of cell differentiation. Dimitriadis et al., pp. 486–494 The best established prognostic factor in colorectal cancer is clinical staging. However, within one clinical stage individual survival rates vary, indicating that subgroups of patients exist with predispositions for early recurrence or resistance to current therapeutic strategies. Dimitriadis and colleagues have identified a new molecule that is associated with frequent metastases, early recurrence and short survival in patients with colorectal cancer. This molecule, CRD-BP/IMP1, is a member of the VICKZ family, which is predominantly expressed during embryonal life. It possesses several recognition motifs for ribonucleoproteins and RNA and is implicated in the posttranslational regulation of several genes, including the F-box protein βTrCP1, which is itself linked to colorectal carcinogenesis. When the authors examined expression of CRD-BP/IMP1 in colorectal tumors, they found that, in 50% of the specimens, the factor was markedly expressed, while only a few cells were immunoreactive in normal tissue. Strikingly, the positive cells in normal tissue were located predominantly at or near the bottom of the crypts, a characteristic localization of stem cells, raising the possibility that CRD-BP/IMP1 is a marker for intestinal stem/progenitor cells. Patients with tumors lacking CRD-BP/IMP1 expression had a favorable clinical outcome. By multivariate analysis the absence of CRD-BP/IMP1 expression was found to be an independent, favorable prognostic factor for survival (p = 0.015). In contrast, CRD-BP/IMP1-positive tumors metastasized or recurred more frequently and characterized a subgroup of patients with shorter survival. These data support the model that abnormal expression of CRD-BP/IMP1 may serve as a useful clinical marker to identify subgroups of patients with a poor prognosis, independently of clinical staging. Menvielle et al., pp. 649–655 Alcohol can cause cancer, including malignancies of the upper aerodigestive tract (oral cavity, pharynx, larynx and esophagus) and liver. Mortality from alcohol-related cancers is often linked to socioeconomic status, with higher death rates in individuals with a lower socioeconomic status. Menvielle and colleagues combined data from longitudinal studies performed in 13 European countries to examine the role of alcohol in socioeconomic inequalities in cancer mortality in men. The contribution of alcohol to socioeconomic inequalities in cancer mortality was 29–36% in France and the Spanish populations, 17–23% in Switzerland and Turin (Italy) and 5–15% in Belgium and the Nordic countries. The difference was most prominent in France, showing the highest mortality rate among men with lower secondary education and the lowest mortality rate among men with a higher education. These results suggest that alcohol use substantially influences socioeconomic inequalities in male cancer mortality in France, Spain and Switzerland but not in the Nordic countries or in Belgium.

Epidemiology of nasopharyngeal carcinoma in the United States: improved survival of Chinese patients within the keratinizing squamous cell carcinoma histology

This study examined potential survival differences among nasopharyngeal carcinoma (NPC) patients from various ethnicities in the United States. A total of 2436 newly diagnosed NPC patients from 1992 to 2002 were analyzed from the population-based Surveillance, Epidemiology, and End Results (SEER) program. Five-year survival rate estimates and Kaplan-Meier survival curves were calculated. Cox proportional hazard ratios (HRs) were used to identify independent prognostic factors for survival. By multivariate analyses, early age of diagnosis, localized stage at presentation (versus distant, HR=0.35; P<0.0001), radiation therapy (versus none; HR=0.48; P<0.0001), undifferentiated non-keratinizing carcinoma (versus keratinizing squamous cell carcinoma; HR=0.67; P<0.0001), and Chinese ethnicity (versus Caucasian; HR=0.78; P=0.0010) were associated with improved survival. Within keratinizing squamous cell carcinoma histology, the survival advantage of Chinese patients remained even after adjustment for other prognostic factors. The significant survival advantage of Chinese NPC patients within the keratinizing squamous cell carcinoma histology contributed largely to Chinese ethnicity being an independent and favorable prognostic factor for survival in NPC.

Survival Benefit with Decitabine Compared to Historical Experience with Intensive Chemotherapy in Patients with Higher Risk Myelodysplastic Syndrome (MDS).

BackgroundDecitabine is a hypomethylating agent, approved by the FDA for treating MDS. Intensive chemotherapy is one treatment option in higher risk MDS. The comparative efficacy of these two strategies, decitabine vs. intensive chemotherapy, has not been evaluated.Study AimsCompare the results of decitabine in MDS with contemporary historical experience with intensive chemotherapy (as used in AML) in patients with higher risk MDS.Study Group and TreatmentThe study group treated with decitabine included 115 patients with higher risk MDS treated on our decitabine frontline study. (Kantarjian, Blood 2006; First Edition Online). The contemporary historical experience included two cohorts:Group A: 115 patients receiving intensive chemotherapy from 1995–2005 and matched for age, IPSS and cytogenetics; andGroup B: All 376 patients treated with intensive chemotherapy from 1995–2005 with similar entry criteria as the decitabine study.Patients received decitabine 20 mg/m2 IV/D x 5 every four weeks. Response was evaluated by the modified IWG criteria (Cheson, Blood 108:419, 2006) In comparing decitabine to Group B, a multivariate analysis was conducted to assess the independent effect of decitabine vs. intensive chemotherapy.Results115 patients were treated with decitabine; median age 64 years (range 37–89 years). IPSS risk groups: intermediate-1 17%, intermediate-2 30%, high 15%, not assessable 39%. Decitabine was given for a median of 7 courses (range 1 to 23); number of decitabine courses 3 or more in 81/89 patients (91%) followed on study for at least 6 months. Hemoglobin <10 g/dL in 76%; thrombocytopenia <100 x 109/L in 72%; ANC <1.0 x 109/L in 47%; chromosomal abnormalities in 63%; prior therapy for MDS in 54%; marrow blast 5% or more in 79%. Overall, 80 patients (70%) achieved IWG response: CR 40 (35%), PR 2 (2%), marrow CR +/− other hematologic improvements (HI) 26 (23%), other HI 12 (10%). Median remission duration was 20 months; median survival was 21 months. The CR rates by AML criteria (Cheson JCO 21:4642, 2003) were 43% with decitabine and 46% with intensive chemotherapy in Group A, and 52% with intensive chemotherapy in Group B. Mortality at 6 weeks was 3% with decitabine vs. 12% with intensive chemotherapy (p=0.002); the 3-month mortality was 7% with decitabine vs. 22% with intensive chemotherapy. The survival was better with decitabine versus intensive chemotherapy in Group A (median 22 month vs. 11 month; estimated 2-year survival rate 47% vs. 25%, p<0.001). A multivariate analysis for survival in all 491 patients receiving decitabine or intensive chemotherapy (Group B) identified the following to be independent adverse factors for survival: abnormal cytogenetics, older age, anemia, thrombocytopenia, and poor performance status. Entering decitabine vs. intensive chemotherapy after accounting for the effect of other prognostic factors selected decitabine as an independent favorable prognostic factor for survival (pvalue 0.002; hazard risk 0.76).ConclusionsCompared with intensive chemotherapy decitabine is associated with a survival benefit in higher risk MDS.

Alterations in the p53 pathway and prognosis in advanced ovarian cancer: A multi-factorial analysis of the EORTC Gynaecological Cancer group (study 55865)

Purpose The study was designed to determine independent prognostic variables in suboptimally debulked advanced ovarian cancer patients entered in the randomised phase III study EORTC 55865. Experimental design Retrospectively collected paraffin blocks from 169 patients with stages IIb–IV epithelial ovarian cancer, taken at primary debulking surgery, were analysed. All patients were treated with cyclophosphamide and cisplatin (CP), and followed up for a median of 10 years. Expression of p53, bcl-2, P21, Ki-67 and HER-2 status was assessed by immunohistochemistry (IHC). Results Expression of p21, a downstream effector of the p53 gene, was found to be a favourable prognostic factor for survival (HR 0.58, CI 0.36–0.94, p = 0.025) in addition to FIGO stage (HR 1.54, CI 1.08–2.21, p = < 0.02). For progression free survival (PFS), both p21 (HR 0.52) and Ki-67 (HR 0.6) were significant factors. Conclusion P21 overexpression is a positive prognostic factor for survival and PFS in advanced ovarian carcinoma with residual lesions of more than 1 cm.

Epidemiology of nasopharyngeal carcinoma (NPC) in California: Survival advantage of Chinese WHO Type 1 NPC patients resulted in Asian ethnicity as an independent and favorable prognostic factor of survival for NPC patients as a whole and for patients with the WHO histologic type 1

5514 Background: We have previously shown that Chinese race is an independent and favorable prognostic factor in NPC survival. We expanded our study to investigate whether Asian ethnicity has the same favorable survival characteristics and if there is a survival difference between Chinese and non-Chinese Asians. Methods: 1,657 newly diagnosed NPC patients from 1992 to 2002 were analysed from the population-based California Cancer Registry. Five year survival rate estimates and Kaplan-Meier curves were calculated. Cox proportional ratios were used to identify independent prognostic factor for survival. Results: The 5-year survival rate of Asian NPC patients was improved compared to non-Asian patients (62% vs 47%; P &lt; .0001). By multivariate analyses, early age of diagnosis, localized stage at presentation (vs distant, HR = 0.41; P &lt; .0001), WHO Type 3 histology (vs Type 1; HR = 0.64; P &lt; .0001), socio-economic status (highest vs lowest quartile; HR = 0.71; P = .0012), use of radiation (vs none; HR = 0.55; P &lt; .0001), and Asian ethnicity (vs Caucasian; HR = 0.82; P = .016) were associated with improved survival. Chinese composed the majority of the Asian ethnicity (49.1%) followed by Filipino (21.2%) and Vietnamese (14.9%). The 5-year survival rate of Chinese was better than non-Chinese Asians (67% vs 56%; P = .0005). When Asian ethnicity was analyzed separately as Chinese and non-Chinese, Chinese retained an overall favorable prognosis (HR = 0.72; P = .0016) whereas non-Chinese Asians did not (HR = 0.91; P = .34). Within each NPC WHO histologic type, early age of diagnosis, localized stage at presentation, and use of radiation were favorable prognostic factors. Chinese (HR = 0.62; P = .0006) but not non-Chinese Asian ethnicity (HR = 0.78; P = .053) was an additional favorable prognostic factor within WHO histologic Type 1. Conclusions: The significant survival advantage of Chinese WHO Type 1 NPC patients resulted in Asian ethnicity being an independent and favorable prognostic factor for survival in NPC. This observation may reflect underlying genetic difference among different racial groups with NPC WHO Type 1. No significant financial relationships to disclose.

Survival benefits of intra-arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma with portal vein tumor thrombosis

: Advanced hepatocellular carcinoma (HCC) with portal vein thrombosis has a poor prognosis. This study was undertaken to evaluate the therapeutic effects of intra-arterial infusion chemotherapy in advanced HCC, and tried to identify prognostic factors that could affect survival. : Between January 1995 and January 2001, a total of 102 patients with advanced HCC with portal vein thrombosis were enrolled and divided into three groups: group 1 (n=24) was managed with only supportive care, group 2 (n=25) received systemic combination chemotherapy and group 3 (n=52) received intra-arterial infusion chemotherapy with 5-fluorouracil+cisplatin via implanted chemoport. : One-year survival rates were 0, 4, 21% and median survivals were 2, 4, 6 months in groups 1, 2, 3, respectively (p=0.003). When we divide group 3 patients into long-term (more than 8 months) or short-term survivors, long-term survivor had significantly low level of serum AST (p=0.032) and alkaline phosphatase (p=0.033). Especially, all female patients (n=9) survived more than 8 months (p=0.000). Other favorable prognostic factors for survival were cirrhosis of Child-Pugh class A (p=0.003), only one major branch involvement of the portal vein by tumor (p=0.005), presence of enhancement of tumor portion in arterial phase of CT scan (p=0.044), presence of enhancement of non-tumor portion in portal phase of CT scan (p=0.029). : Intra-arterial infusion chemotherapy achieved favorable results in advanced HCC with portal vein thrombosis and showed better survival in selected patients.

Survival benefit with imatinib mesylate therapy in patients with accelerated‐phase chronic myelogenous leukemia—Comparison with historic experience

The effect of imatinib mesylate on survival in the accelerated phase of chronic myelogenous leukemia (CML) is unknown. The objectives of this study were to update the long-term experience with imatinib in patients who had accelerated-phase CML and to compare outcomes with historic experience. The outcomes of 176 patients who received treatment with imatinib were reviewed and compared with the outcomes of 213 historic control patients with accelerated-phase CML who received treatment with interferon-alpha or with other modalities. With imatinib, the complete hematologic response rate was 82% versus a rate < or = 50% for others, and the complete cytogenetic response rate was 43% versus rates of 0-6% for others. The estimated 4-year survival rates were 53% with imatinib, 42% with interferon-alpha, and 0-21% for others. A multivariate analysis of the total population of 389 patients indicated that imatinib therapy (vs. other therapies) was an independent, favorable prognostic factor for survival (P < 0.0001; hazard rate, 0.62). A subset analysis that included only patients who were treated with imatinib and interferon-alpha (276 patients) also identified imatinib as an independent favorable prognostic factor (P < 0.0001; hazard rate, 0.65). The 3-month cytogenetic response to imatinib was associated with significantly different survival outcomes (P < 0.0001). A multivariate analysis that included pretreatment characteristics and 3-month cytogenetic response among 150 patients who received imatinib and were alive at 3 months identified only 2 adverse independent prognostic factors: lack of a cytogenetic response at 3 months (P < 0.001) and anemia (hemoglobin < 10 g/dL; P = 0.003). Patients who had neither factor (41%) had an estimated 4-year survival rate of 88%; in the other patients, the 4-year survival rate was < or = 60%. This may have implications in relation to subsequent therapy, because, according to the outcomes of patients who underwent allogeneic transplantation in accelerated phase at the authors' institution and from literature reports, the estimates of 5-year survival were 25-30%. The current results suggest that imatinib improved survival compared with other therapies in patients with accelerated-phase CML.

Chemotherapy for patients with two favourable subsets of unknown primary carcinoma: Active, but how effective?

Carcinoma of unknown primary (CUP) is characterized by dismal patient survival. The outcome of patients with two favourable risk CUP subsets was studied. Eighty patients diagnosed with either midline lymph node metastases (n=33) or peritoneal carcinomatosis (n=47) were analysed retrospectively. The majority had poorly differentiated adenocarcinoma or undifferentiated carcinoma, treated with platinum-taxane based chemotherapy from 1996 till 2002. Females with peritoneal carcinomatosis also underwent surgical debulking. Objective tumour regression was present in 44% of patients (nodal group 30% versus peritoneal group 53%, p=0.066). Complete responses were seen more often in peritoneal carcinomatosis patients (nodal group 9%, peritoneal group 36%, p=0.008). At a median follow up of 60 months, median progression-free and overall survival were 5 and 10 months respectively in the nodal group, 7 and 15 months in the peritoneal group. Five-year survival was 7% (nodal group 0% vs. peritoneal group 10%, p=0.05). Complete responders fared better than non-CR patients. Fewer than four metastatic sites, elevated CA 125, and normal CA 19-9 levels were favourable prognostic factors for survival. Modern combination chemotherapy has satisfactory activity, with a minority of CUP patients enjoying long-term responses. Research efforts towards complete remission consolidation and molecular profiling are imperative.