Adverse Prognostic Factor For Overall Survival Research Articles

Pre-existing type 2 diabetes mellitus is an independent risk factor for mortality and progression in patients with renal cell carcinoma.

Malignancies are one of the main causes of mortality in diabetic patients; however, to date, very limited data have been reported on the specific influence of type 2 diabetes mellitus (T2DM) on the survival of patients with renal cell carcinoma (RCC). In the present long-term retrospective study, we investigated whether T2DM may influence the overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) in patients with surgically treated RCC.Medical records of 924 patients treated by radical or partial nephrectomy for sporadic, unilateral RCC were reviewed. Patients with type-1 DM and with T2 DM receiving insulin treatment were excluded. Survival estimates were calculated according to the Kaplan–Meier method and compared with the log-rank test. Univariate and multivariate analyses were performed using the Cox regression model.Of the 924 RCC patients, 152 (16.5%) had T2DM. Mean follow-up was 68.5 months. Mean OS was 41.3 and 96.3 months in T2DM and non-T2DM patients, respectively (P < 0.0001).The estimated CSS rates at 1, 3, and 5 years in T2DM versus non-T2DM patients were 63.4% versus 76.7%, 30.4% versus 56.6%, and 16.3% versus 48.6%, respectively (P = 0.001). Mean PFS was significantly lower (31.5 vs 96.3 months; P < 0.0001) in the T2DM group. At multivariate analysis, T2DM was an independent adverse prognostic factor for OS (hazard ratio [HR] = 3.44; 95% confidence interval [CI]:2.40–4.92), CSS (HR = 6.39; 95% CI: 3.78–10.79), and PFS (HR = 4.71; 95% CI: 3.11–7.15).In conclusion, our findings suggest that patients with RCC and pre-existing T2DM have a shorter OS, increased risk of recurrence, and higher risk for kidney cancer mortality than those without diabetes.

Nasopharyngeal carcinoma in children and adolescents - a single institution experience of 158 patients.

BackgroundTo evaluate the clinical features, treatment results, prognostic factors and late toxicities of nasopharyngeal carcinoma in children and adolescents.MethodsBetween January 1990 and January 2011, 158 NPC patients younger than 20 years old were treated in our institution, and the patient’s clinical characteristics, treatment modalities, outcomes and prognostic factors were retrospectively analyzed.ResultsThere were 9 (5.7%) patients in stage II, 60 (38.0%) in stage III and 89 (56.3%) in stage IV according to the UICC2002 staging system. Neck mass (32.3%), headache (21.5%) and nasal obstruction (15.2%) were the most common chief complaints. With a median follow-up time of 62.5 months (range 2.0-225.0 months), the 5-year overall survival (OS) rate, local-regional control (LRC) rate and distant metastasis-free survival (DMFS) rate were 82.6%, 94.9% and 76.4%, respectively. There were 43 (27.2%) patients failed during the follow up, with seven local-regional recurrences and 38 distant metastases. In univariate analysis, the 5-year OS of T4 and T1-3 were 75% and 87.9%, p = 0.01, stage IV and stage II-III were 77.1% and 90%, p = 0.04, respectively. In multivariate analysis, T4 (p = 0.02) and stage IV (p = 0.04) were the independent adverse prognostic factors for OS. Significant reduction in trismus (27.3% v 3.6%, p = 0.03) and G2 xerostomia (37.9% v 10.3%, p = 0.02) was observed in patients treated by IMRT.ConclusionsMost childhood and adolescence nasopharyngeal carcinoma patients were locally advanced diseases at first diagnosed. The treatment results of radiotherapy, with or without chemotherapy, are excellent in our institution. Reducing distant metastasis with new strategies and late toxicities with intensity-modulated radiotherapy are the future directions for the treatment of adolescent nasopharyngeal carcinoma.

Old DAT and new data: positive direct antiglobulin test identifies a subgroup with poor outcome among chronic lymphocytic leukemia stage A patients.

Only a minority of chronic lymphocytic leukemia (CLL) patients harboring a positive direct antiglobulin test (DAT) will develop autoimmune hemolytic anemia (AIHA). In a single institution cohort of 378 CLL patients, 56 patients (14.8%) had at least one positive DAT during the course of the disease, either at diagnosis or later. We found no relationship between the time of the first positive DAT and overall survival (OS). However, patients with a positive DAT who did not develop AIHA had the same adverse outcome as patients who developed AIHA. Of the patients who were in Binet stage A at diagnosis, those with a positive DAT had a significantly shorter OS, regardless of their IGHV mutational status, however, there was a strong association with VH1-69. By multivariate analysis, a positive DAT was found to be an independent adverse prognostic factor for OS. Thus, DAT represents a strong adverse prognostic factor and its determination should be repeated during follow-up.

First-line anthracycline-based chemotherapy for angiosarcoma and other soft tissue sarcoma subtypes: Pooled analysis of eleven European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group trials

BackgroundAngiosarcoma is a rare subtype of soft tissue sarcoma (STS). Doxorubicin is the standard first-line chemotherapy for advanced STS. It is not known whether angiosarcoma response to anthracycline-based chemotherapy is different to other STS subtypes. MethodsPooled data were analysed from 11 prospective randomised and non-randomised European Organisation for Research and Treatment of Cancer (EORTC) clinical trials of first-line anthracycline-based chemotherapy for advanced STS. Baseline patient characteristics, chemotherapy response, progression free survival (PFS) and overall survival (OS) of angiosarcoma patients were compared with other STS patients. Analysis was performed to identify factors prognostic for angiosarcoma response to chemotherapy, PFS and OS. ResultsWith a median follow-up of 4.2years, data from 108 locally advanced and metastatic angiosarcoma patients and 2557 patients with other STS histologies were analysed. 25% of angiosarcoma patients had a complete or partial response to chemotherapy compared to 21% for other STS histotypes. The median PFS was 4.9months and OS 9.9months, which were not significantly different from other STS histotypes. In univariate analysis, bone metastases were an adverse prognostic factor for OS (hazard ratio (HR) 1.66, 95% confidence interval (CI) 1.03–2.67; p=0.036). Tumour grade was as an adverse prognostic factor for PFS (HR 1.72, 95% CI 1.01–2.92; p=0.044) and OS (HR 2.03; 95% CI 1.16–3.56; p=0.011). Compared to single agent anthracyclines, doxorubicin+ifosfamide was associated with improved PFS (HR 0.53, 95% CI 0.33–0.86; p=0.010) and OS (HR 0.53, 95% CI 0.32–0.90; p=0.018). ConclusionsAngiosarcoma response and survival following first-line anthracycline-based chemotherapy was similar to other STS histotypes. Our analysis provides a useful measure of angiosarcoma response to chemotherapy for comparison with future clinical trials.

Nasopharyngeal Carcinoma in Childhood and Adolescence: A Single Institution’s Experience of 158 Patients

Nasopharyngeal Carcinoma in Childhood and Adolescence: A Single Institution’s Experience of 158 Patients

Inverse effect of mucinous component on survival in stage III colorectal cancer.

Although mucinous adenocarcinoma (MAC) is has been recognized as a separate entity in colorectal cancer (CRC), adenocarcinoma with a mucinous component (ACM) remains poorly understood. The association of MAC and ACM with disease-free survival (DFS) and overall survival (OS) was examined using the Cox proportional hazard model in 425 consecutive stage III CRCs. Compared with conventional adenocarcinoma (CAC), patients with MAC exhibited independently worse DFS (hazard ratio [HR], 2.64; 95% CI, 1.21-5.80; P = 0.014) and OS (HR, 3.56; 95% CI, 1.53-8.30; P = 0.003). Unexpectedly, ACM was significantly associated with worse OS than CAC (P = 0.002), despite having a similar DFS to CAC. Further, ACM patients after recurrence exhibited significantly worse OS than CAC patients (P < 0.001), similar to MAC. Although ACM is similar to CAC with regard to estimated risk of recurrence, the outcome is extremely poor once recurrence occurs and is identical to MAC; one of the most aggressive phenotypes of stage III CRC. Thus, both MAC and ACM are adverse prognostic factors for OS.

Serum anti-osteopontin autoantibody as a novel diagnostic and prognostic biomarker in patients with hepatocellular carcinoma.

Osteopontin (OPN) is a secreted phosphorylated and glycosylated protein, which plays an important role in carcinogenesis and metastasis. In hepatocellular carcinoma (HCC), OPN is being investigated either as a therapeutic target gene or as a biomarker for diagnosis. Yet, the role of the anti-OPN autoantibody in HCC remains unclear. In the present study, the level of serum anti-OPN autoantibody in HCC was analyzed by enzyme-linked immunosorbent assay. Immunohistochemistry (IHC) was also performed to analyze protein expression profiles and the prognostic significance of OPN in HCC. In this study, the prevalence and titer of anti-OPN autoantibodies in HCC were significantly higher than these values in normal human serum (NHS) (P=0.001, P=0.000, respectively). When both α-fetoprotein and the autoantibody against OPN were used simultaneously as diagnostic biomarkers, the sensitivity was up to 65%. In IHC, 59 of the 83 (65.6%) HCC specimens expressed OPN with cytoplasmic positive staining. The overall survival (OS) of HCC patients with OPN-positive tumors was 28.81 months compared to 39.37 months for HCC patients with OPN-negative tumors (P<0.01). Furthermore, multivariate analysis showed that OPN overexpression was the strongest independent adverse prognostic factor for OS (P=0.02). Taken together, our data indicate that the anti-OPN autoantibody may be a supplementary serological biomarker for HCC, and is correlated with poor prognosis in HCC patients.

Prognostic significance of lymphovascular invasion in patients with esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy.

To investigate the prognostic significance of lymphovascular invasion (LVI) in patients with esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (nCRT). We retrospectively reviewed the charts of 416 consecutive patients with ESCC who underwent surgical resection following nCRT at the Chang Gung Memorial Hospital between 1998 and 2008. After exclusion of patients with non-R0 resection or showing no residual tumor (ypT0Nx), the histological tumor sections of 231 patients were reviewed for LVI. Univariate and multivariate analyses were used to identify the independent predictors of overall survival (OS). LVI was observed in 85 patients (36.8 %). The presence of LVI was related to close circumferential resection margins (CRMs), a greater depth of invasion, poor tumor differentiation, and an increased occurrence of lymph node metastases (LNM). The 5 year OS was significantly lower (10 %) in patients with LVI than in those without (31 %; p < 0.001). By multivariate Cox regression analyses, LVI (hazard ratio [HR] 1.5; p = 0.002) and LNM (HR 1.6; p = 0.007) were identified as independent adverse prognostic factors for OS. The 5 year OS rates according to the number of risk factors present were 35, 21, 20, and 5 for LVI(-)LNM(-), LVI(+)LNM(-), LVI(-)LNM(+), and LVI(+)LNM(+) patients, respectively (p < 0.001). The presence of LVI is independently associated with shorter OS in ESCC patients receiving nCRT. Links between LVI and LNM may provide new clues for the prognostic stratification of esophageal cancer.

The presence of extrathoracic metastasis is more prognostic of survival than Masaoka stage (IVa/IVb) in metastatic thymic epithelial tumor: A retrospective cohort study

PurposeOur aim in this study was to identify independent prognostic factors for overall survival (OS) in order to explain the heterogeneity of OS in patients with metastatic thymic epithelial tumor (TET). MethodsSixty-one consecutive patients with histologic diagnosis of Masaoka stage IV TET between January 1980 and March 2009 were analyzed at a single institution. Masaoka stage IVa was defined as pleural or pericardial dissemination, and IVb as lymphogenous or hematogenous metastasis. Metastasis outside the thoracic cage was defined as extrathoracic metastasis. To identify prognostic factors, relationships between clinicopathologic factors and outcomes were analyzed. ResultsOf the 61 patients, 30 (49.2%) had thymoma, 28 (45.9%) had thymic carcinoma, and the remaining 3 (4.9%) had an unclear histologic subtype. The Masaoka stage was IVa in 27 patients (44.3%) and IVb in 34 patients (55.7%). Significant independent adverse prognostic factors for OS were histologic subtype and extrathoracic metastasis (hazard ratio [HR]=3.09 and 6.03, 95% CI: 1.41–6.74 and 1.89–19.30, p=0.005 and 0.002, respectively). The presence of extrathoracic metastasis was also an independent prognostic factor for decreased progression-free survival time (PFS) (HR=6.62, 95% CI: 1.19–24.17, p=0.004). The only significant criterion for prognostic discrimination was the presence of extrathoracic metastasis in metastatic TET. ConclusionsSignificant independent prognostic factors for lower OS were the histologic subtype of thymic carcinoma and the presence of extrathoracic metastasis. A new concept of extrathoracic metastasis might provide additional information for the understanding of metastatic TET.

Peripheral blood lymphocyte/monocyte ratio at the time of first relapse predicts outcome for patients with relapsed or primary refractory diffuse large B-cell lymphoma.

BackgroundDespite the use of modern immunochemotherapy regimens, a significant proportion of diffuse large B-cell lymphoma (DLBCL) patients will relapse. We proposed absolute lymphocyte count/absolute monocyte count ratio (ALC/AMC ratio) as a new prognostic factor in relapsed or primary refractory DLBCL.MethodsWe retrospectively analyzed 163 patients who have been diagnosed with relapsed or primary refractory DLBCL. The overall survival (OS) and progression-free survival (PFS) were measured from the time of first relapse. The Cox proportional hazards model was used to evaluate ALC/AMC ratio as prognostic factors for OS and PFS.ResultsOn univariate and multivariate analysis performed with factors included in the saaIPI, early relapse, prior exposure to rituximab and autologous stem-cell transplantation (ASCT), the ALC/AMC ratio at the time of first relapse remained an independent predictor of PFS and OS (PFS: P < 0.001; OS: P < 0.001). Patients with lower ALC/AMC ratio (<2.0) had lower overall response rate, 1-year PFS and 2-year OS rate compared with those with higher ALC/AMC ratio (≥2.0). Moreover, the ALC/AMC ratio can provide additional prognostic information when superimposed on the saaIPI.ConclusionsLower ALC/AMC ratio at the time of first relapse is a adverse prognostic factor for OS and PFS in relapsed or primary refractory DLBCL, and leads to the identification of high-risk patients otherwise classified as low/intermediate risk by the saaIPI alone.

Safety and efficacy of gemcitabine or pemetrexed in combination with a platinum in patients with non-small-cell lung cancer and prior interstitial lung disease

The incidence of lung cancer in patients with interstitial lung disease (ILD) is higher than in the general population; however, the clinical benefit of chemotherapy and the appropriate regimen for non-small-cell lung cancer (NSCLC) patients with ILD remain unclear. This study was conducted to elucidate the safety and efficacy of palliative chemotherapy with gemcitabine or pemetrexed, both in combination with a platinum agent in NSCLC patients with ILD. Patients with advanced or recurrent NSCLC and ILD who received gemcitabine or pemetrexed in combination with a platinum agent as first-line chemotherapy were retrospectively analyzed. Clinical outcomes, including response rate, overall survival (OS), and progression-free survival (PFS), in addition to the acute exacerbation of ILD after chemotherapy were investigated. Between January 2007 and December 2011, 52 patients were analyzed. The median age at chemotherapy was 67. Thirty-two patients (61.5 %) had adenocarcinoma histology. With respect to the types of ILD, idiopathic interstitial pneumonia (IIP) and non-IIP were observed in 42 (80.8 %) and 10 (19.2 %) patients, respectively. The FEV1 level was less than 80 % of the predicted value in 15 of the 41 patients in whom it was measured. The overall response rate was 42.3 % (95 % CI 28.8-55.9), and the median PFS was 5.4 months (95 % CI 4.6-6.2). The median OS was 7.9 months (95 % CI 5.5-10.3), and the 1-year survival rate was 31.7 % (95 % CI 19.0-44.4). Eight patients (15.4 %) died within 3 months of first-line chemotherapy. Multivariate analysis demonstrated that a heavy smoking history (40 or more pack-year smoking history) was an independent adverse prognostic factor for OS. An acute exacerbation of ILD (AE-ILD) caused by first-line chemotherapy was noted in 5.8 % of patients. Our results suggest that gemcitabine or pemetrexed in combination with platinum agents could be a feasible option for advanced NSCLC with ILD with some risk of AE-ILD or early death. To establish the efficacy of palliative chemotherapy for patients with NSCLC and ILD, further well-controlled prospective studies are needed.

Clinical and pathological features of patients with resected synovial sarcoma: a multicenter retrospective analysis of the Anatolian Society of Medical Oncology.

Synovial sarcoma (SS) is a rare disease and compared with other soft-tissue sarcomas has a relatively high mortality rate. The optimal management of this disease and prognostic factors associated with patient outcome remains controversial. We aimed to evaluate the factors affecting the outcomes of SS patients in the adjuvant setting. In this Turkish multicenter study, we assessed the data of 69 SS patients regarding prognostic factors for SS patients retrospectively. Our study included 69 localized SS patients (38 males and 31 females) with a median age of 34.5 years (minimum-maximum: 14-68 years). Overall survival (OS) and disease free survival (DFS) rates for 5 years were 64% and 25%, respectively. All patients under went surgical treatment; 64 patients were treated with a wide excision and 5 patients had an amputation. According to the univariate analysis, adverse prognostic factors for OS were male sex, higher mitotic activity, high Ki-67 levels, trunk localization and inadequate surgical margins. In multivariate analysis, none of these factors had independent significant association with OS. Prognostic factors for DFS; in the univariate analysis were higher mitotic activity, high Ki-67 levels and inadequate surgical margins. Only higher mitotic activity (≥10 high-power field) was significantly associated with worse DFS in the multivariate analysis (hazard ratio: 0.30, % confidence interval: 0.11-0.80, P = 0.017). Our study confirms that high mitotic activity is significantly associated with decreased DFS. The question of whether the chemotherapy provides a survival advantage in patients having adverse prognostic factors requires confirmation in randomized trials.

Vascular Cell Adhesion Molecule-1 Is An Independent Prognostic Factor For Newly-Diagnosed Patients With Multiple Myeloma; Reductions Post VD and Rd In Myeloma Patients At First Relapse

The adherence of myeloma cells to the bone marrow stromal cells plays a key role in the biology of the disease as it supports the growth of myeloma cells in the marrow microenvironment. The aim of our study was to evaluate the levels of circulating adhesion molecules in myeloma patients, to explore possible correlations with disease characteristics, including survival, and to examine their alterations post-therapy with novel agents. We measured circulating levels of vascular cell adhesion molecule-1 (VCAM-1; CD106), intercellular adhesion molecule-1 (ICAM-1; CD54), P-, L- and E-selectin using an ELISA methodology (R&D Systems, Minneapolis, MN, USA) in 232 consecutive myeloma patients: 145 with newly diagnosed symptomatic MM (NDMM) who were treated with novel agent based therapies and 87 with relapsed myeloma (RMM) at first relapse. Of the later, 47 received lenalidomide with low-dose dexamethasone (Rd) and 40 patients received bortezomib with dexamethasone (VD). Serum was collected just before initiation of therapy for NDMM patients, or before initiation of the first Rd or VD cycle (on day 1) for RMM patients and after the completion of the 4thcycle of Rd or VD (on day 28 or 21, respectively).Patients with NDMM had increased circulating levels of VCAM-1 and ICAM-1 compared to controls (n=17, p<0.001 for all comparisons), while the levels of selectins did not differ between MM patients and controls. VCAM-1 was lower in patients with ISS-1 [590 ng/ml (range: 312-869 ng/ml)] compared to patients with ISS-2 [639ng/ml (226-4163ng/ml)] and ISS-3 [1189 ng/ml (288-2997ng/ml), ANOVA p=0.002). For NDMM patients, there was a positive correlation between VCAM-1 and ICAM-1 (r=0.466, p<0.001) and a negative correlation between VCAM-1 and P-selectin (r=-0.216, p<0.001). Serum VCAM-1 showed also strong correlation with β2-microglobulin (r=0.560, p<0.001) and serum creatinine (r=0.436, p<0.001) but had not correlation with the extent of marrow infiltration by plasma cells.The median follow-up of symptomatic patients with NDMM was 31 months and the median overall survival (OS) was 53 months (CI 95% 46-59 months). The median progression-free survival (PFS) for all patients was 23 months; patients who had VCAM-1 values >median had a median PFS of 19 months vs. 32 months of the others (p<0.0001). Importantly, VCAM-1 was an independent prognostic factor for PFS in the multivariate analysis (VCAM-1 >median was associated with a HR: 2.17, CI 95%: 1.18-4, p=0.012). Increased levels of VCAM-1 (>median) were also associated with inferior survival. In particular, patients with high VCAM-1 had a median OS of 45 months vs. 75 months for those with levels <median (p=0.001). As continuous variable, increasing levels of VCAM-1 correlated with shorter OS (p=0.003). Other adverse prognostic factors for OS in the univariate analysis included: advanced ISS stage (p=0.026), LDH ≥300 U/L (p<0.001) and platelet counts (<150x109/l, p<0.001). In the multivariate analysis, VCAM-1 >median (HR: 2.46, CI 95%: 1.06-5.68, p=0.034) had an independent prognostic value for inferior survival.MM patients at first relapse had increased levels of ICAM-1 and L-selectin even compared to newly-diagnosed symptomatic MM patients (p=0.001 and p=0.017, respectively) and increased levels of VCAM-1 compared to controls (p<0.01 for all comparisons). Both VD and Rd reduced dramatically serum VCAM-1 after 4 cycles of therapy (p<0.001 and p=0.008 respectively), but only VD reduced serum ICAM-1 (p=0.001). The reduction of VCAM-1 was more pronounced after Rd than after VD (median % reduction: 38% vs. 17%; p=0.002). Therapy with Rd increased P-selectin and decreased L- and E-selectin (p≤0.01 for all comparisons), while VD had no effect on selectins. All changes were independent of response to therapy.Our study provides evidence about the role of microenvironment in the outcome of myeloma patients. In particular, VCAM-1 had an independent prognostic value for both PFS and OS in patients with newly-diagnosed symptomatic disease who were treated with novel agent-based therapies. Interestingly, in patients at first relapse, both Rd and VD produced a dramatic reduction of VCAM-1, irrespective of response to treatment indicating an effect of these drugs on the microenvironment, while Rd altered also the levels of all studied selectins suggesting an effect of Rd on the vascular niche and the endothelium. Disclosures:No relevant conflicts of interest to declare.

Clinical Outcomes and Prognostic Factors Associated with the Response to Erlotinib in Non-Small-Cell Lung Cancer Patients with Unknown EGFR Mutational Status

The efficacy of erlotinib is controversial in patients with unknown EGFR mutational status. The aim of this study was to identify the clinicopathological factors that are predictive of erlotinob treatment outcomes for NSCLC patients with unknown EGFR mutational status. A retrospective analysis of 109 patients with advanced NSCLC who had previously failed at least one line of chemotherapy and received subsequent treatment with erlotinib (150 mg/day orally) was performed. A Cox proportional hazard model for univariate and multivariate analyses was used to identify the baseline clinical parameters correlating with treatment outcome, expressed in terms of hazard ratios (HRs) and 95% confidence intervals. The median treatment duration was 15 weeks (range, 4-184). The disease control rate was 55%, including disease stability for ≥ 3 months for 40% of the patients. Median progression-free survival and median overall survival (OS) were 4.2 and 8.5 months, respectively. The Cox model indicated that an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2 (HR 3.82; p<0.001), presence of intra-abdominal metastasis (HR 3.42; p=0.002), 2 or more prior chemotherapy regimens (HR 2.29; p=0.021), and weight loss >5% (HR 2.05; p=0.034) were independent adverse prognostic factors for OS in NSCLC patients treated with erlotinib. This study suggests that NSCLC patients should be enrolled in erlotinib treatment after a first round of unsuccessful chemotherapy to improve treatment success, during which they should be monitored for intra-abdominal metastasis and weight loss.

Prognostic role of tumor-associated macrophages and angiogenesis in classical Hodgkin lymphoma

We studied by immunohistochemistry CD68 + tumor-associated macrophages (TAMs) and angiogenesis in 121 consecutive cases of uniformly treated classical Hodgkin lymphoma (cHL). High TAM count showed a significant correlation with age ≥ 45, mixed cellularity subtype and high β2-microglobulin level. Vessel density (VD) was unrelated to clinicopathological features, while a significant correlation was found between TAM count and VD. Patients with high TAMs showed a trend toward reduced progression-free survival and significantly shorter overall survival (OS). No correlation was found between VD and survival. At multivariate analysis, bulky disease was an independent predictor of reduced progression-free survival, while independent adverse prognostic factors for OS were male sex, age ≥ 45, advanced stage and bulky disease. High TAM count results in an adverse overall outcome in cHL and is significantly correlated to VD. Since VD has no prognostic relevance, the adverse effect of TAMs is presumably unrelated to angiogenesis.

Genetic Profiling Identifies Two Classes of Soft-Tissue Leiomyosarcomas with Distinct Clinical Characteristics

Data about the prognostic factors of soft-tissue leiomyosarcomas and their correlation with molecular profile are limited. From 1990 to 2010, 586 adult patients with a primary soft-tissue leiomyosarcoma were included in the French Sarcoma Group (GSF) database after surgery of the primary tumor. Multivariate analyses were conducted by Cox regression model in a backward stepwise procedure. Genetic profiling was conducted for 73 cases. Median age was 59 years (range, 21-98 years). The median follow-up of patients alive was 46 months. The 5-year metastasis-free survival (MFS) rate was 51% (95% location and grade > I were independent adverse prognostic factors for MFS). The 5-year overall survival (OS) rate was 63% [95% confidence interval (CI), 59-67]. On multivariate analysis, age ≥ 60 years old, tumor size > 5 cm, deep location, and grade > I were independent adverse prognostic factors for OS. Molecular profiling identified specific clusters with activation of different biologic pathways: retroperitoneal leiomyosarcomas are characterized by overexpression of genes involved in muscle differentiation and nonretroperitoneal leiomyosarcomas characterized by overexpression of genes mainly involved in extracellular matrix, wounding, and adhesion pathways. The CINSARC signature but not comparative genomic hybridization (CGH) profiling was predictive of outcome. Soft-tissue leiomyosarcomas represent a heterogeneous group of tumors with at least two categories, retroperitoneal and extremities leiomyosarcomas, having specific clinical outcome and molecular features. Future clinical trials should consider this heterogeneity for a better stratification of patients.

Prognostic Factors for Patients with Diffuse Large B Cell Lymphoma and Transformed Indolent Lymphoma Undergoing Autologous Stem Cell Transplantation in the PET Era

Abstract 1980▪▪This icon denotes a clinically relevant abstractHigh dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains the standard of care for patients with relapsed or refractory (R/R) diffuse large B cell lymphoma (DLBCL) who are chemosensitive to salvage therapy. There is now evidence that the achievement of complete remission by PET scan (PET-CR) after salvage therapy is a favorable determinant of ASCT outcome, implying that PET response should be part of the prognostic assessment for patients considering ASCT. However, it is unclear whether other prognostic factors are still relevant in patients getting post-salvage PET scanning. Moreover, while ASCT is often also used for patients with R/R transformed indolent lymphoma (TIL), there are no data on whether prognostic factors that are important for DLBCL patients, especially PET response to salvage, are similarly prognostic in this population.We studied 163 consecutive adult patients who underwent ASCT at 2 institutions over the last decade for R/R DLBCL (122 patients) or R/R TIL (41 patients) and had a post-salvage PET scan. 98% were chemosensitive after salvage by conventional criteria. Among the 122 patients with DLBCL, 52 (43%) remained PET positive after salvage. PET-positivity was more likely for patients with advanced stage at relapse, and for those whose first remission duration was less than 6 months. After a median follow-up of 49 months from ASCT, the 4-year overall survival (OS) for PET-positive patients was 54% versus 74% for PET-negative patients (p=0.016), while the corresponding 4-year progression-free survival (PFS) was 30% versus 63% (p<0.0001). In multivariable models, the following were adverse prognostic factors for OS and PFS: PET positivity after salvage, age ≥60 years, CNS involvement at relapse, symptomatic relapse, and advanced stage at relapse (for OS only). Based on those factors, we constructed a prognostic score, assigning 1 point for each of the above factors (except for CNS relapse which was assigned 3 points). Patients in the low-risk group (0–1 points) had a 4y OS of 90% and 4y PFS of 74%, compared to 63% and 45% for patients in the intermediate-risk group (2–3 points), and 19% and 0% for patients in the high-risk group (4+ points) (p<0.0001 for both OS and PFS differences) (Figure 1A).The post-ASCT outcome of patients with TIL was not significantly different from that of DLBCL patients (4y OS 53% versus 69%, p=0.23, and 4y PFS 44% versus 54%, p=0.4). Notably, in this group, PET status after salvage had no prognostic relevance (Figure 1B). In fact, in multivariable models for OS and PFS, only short duration of 1st remission and elevated LDH at relapse (for OS only) were significant. [Display omitted] This study confirms the prognostic importance of post-salvage PET remission status. However, If PET response is included in the prognostic assessment, traditional risk factors such as receipt of 1st line rituximab, short duration of 1st remission, or elevated second-line aaIPI appear to lose their prognostic importance. Instead, we identified 4 other clinical factors that were strongly associated with outcome: advanced age, CNS relapse, advanced stage at relapse, and symptomatic relapse. Our prognostic score is simple to calculate and stratifies patients into 3 groups with significantly different OS and PFS. An important potential use of this score, if further validated, could be to identify a high-risk population whose outcomes after ASCT are dismal (0% PFS and 19% OS at 4 years), and who should be considered for alternative treatment approaches. Moreover, our results suggest that prognostic factors for patients with TIL may be entirely different; in particular, PET response to salvage may not be prognostically important. This is important to consider when designing clinical trials or interpreting their results in this patient population. Disclosures:No relevant conflicts of interest to declare.

Membranous expression of activated leukocyte cell adhesion molecule contributes to poor prognosis and malignant phenotypes of non–small-cell lung cancer

BackgroundActivated leukocyte cell adhesion molecule (ALCAM) has been shown to correlate with the prognosis of patients with various types of human malignancies. However, the relationship between ALCAM expression and progression of non–small-cell lung cancer (NSCLC) has not been investigated. This study was designed to clarify the prognostic impact of ALCAM expression of NSCLC cells. Materials and methodsThe study population consisted of 147 NSCLC patients who underwent complete resection. We performed immunohistochemical staining for ALCAM expression and correlated this to the clinicopathologic parameters and patient survival. The ALCAM expression in NSCLC cell lines was analyzed using quantitative reverse transcription–polymerase chain reaction and Western blot analyses. ALCAM knockdown in NSCLC cell lines was performed with lentivirus-mediated short hairpin RNA transduction. ResultsPositive membranous and cytoplasmic ALCAM expressions were detected in 66 (44.9%) and 57 (38.8%) patients, respectively. A significant association of high membranous ALCAM expression with shortened overall survival (OS) was found (P = 0.009). However, patients with cytoplasmic staining of ALCAM showed no significantly shortened OS (P = 0.723). Multivariate analyses showed that membranous expression was adverse prognostic factors for OS (hazard ratio, 2.11; P = 0.046). ALCAM knockdown with short hairpin RNA suppressed cell migration and invasion of NSCLC cell lines in vitro. ConclusionsStrong membranous ALCAM expression is associated with a poor prognosis in patients with resected NSCLC, and overexpression of ALCAM causes malignant phenotypes of NSCLC.

Clinical significance of genetic aberrations in secondary acute myeloid leukemia

The study aimed to identify genetic lesions associated with secondary acute myeloid leukemia (sAML) in comparison with AML arising de novo (dnAML) and assess their impact on patients' overall survival (OS). High-resolution genotyping and loss of heterozygosity mapping was performed on DNA samples from 86 sAML and 117 dnAML patients, using Affymetrix Genome-Wide Human SNP 6.0 arrays. Genes TP53, RUNX1, CBL, IDH1/2, NRAS, NPM1, and FLT3 were analyzed for mutations in all patients. We identified 36 recurrent cytogenetic aberrations (more than five events). Mutations in TP53, 9pUPD, and del7q (targeting CUX1 locus) were significantly associated with sAML, while NPM1 and FLT3 mutations associated with dnAML. Patients with sAML carrying TP53 mutations demonstrated lower 1-year OS rate than those with wild-type TP53 (14.3% ± 9.4% vs. 35.4% ± 7.2%; P = 0.002), while complex karyotype, del7q (CUX1) and del7p (IKZF1) showed no significant effect on OS. Multivariate analysis confirmed that mutant TP53 was the only independent adverse prognostic factor for OS in sAML (hazard ratio 2.67; 95% CI: 1.33-5.37; P = 0.006). Patients with dnAML and complex karyotype carried sAML-associated defects (TP53 defects in 54.5%, deletions targeting FOXP1 and ETV6 loci in 45.4% of the cases). We identified several co-occurring lesions associated with either sAML or dnAML diagnosis. Our data suggest that distinct genetic lesions drive leukemogenesis in sAML. High karyotype complexity of sAML patients does not influence OS. Somatic mutations in TP53 are the only independent adverse prognostic factor in sAML. Patients with dnAML and complex karyotype show genetic features associated with sAML and myeloproliferative neoplasms.

Survival comparison between malignant lymphoma HIV+ versus HIV- in the post HAART era: INEN 2005-2011.

e18524 Background: The incidence of non-Hodgkin lymphoma in HIV patients (ARLs) is higher than in general population. In the HAART era AIDS-related lymphoma (ARL) are more frequent in patients with advanced age, delayed diagnosis, non adherent HAART, multiresistant strains of HIV. The aim of this study is to compare the clinical characteristic, prognosis factors and survival of malignant lymphomas HIV( +) vs HIV(-) at the Instituto Nacional de Enfermedades Neoplásicas. Methods: Study retrospective, individually matched, case-controlled study according to HIV serologic status (positive vs negative) for patiens newly diagnosed of non-Hodgkin lymphoma between 2005 and 2011. Results: We included 51 cases HIV (+) and 102 controls HIV (-) (Table). On diagnosis, anemia (Hemoglobin &lt; 110 g/L) and opportunistic infections (OI) were statiscal more frequent (p&lt;0.05) in ARL. The overall response to chemotherapy (ORC) was 76.4% (cases) and 89.2% (controls) (p&lt;0.05). In multivariate analysis ECOG ≥ 2, OI and no response to chemotherapy increase mortality risk in ARL (p&lt;0.05). ARL had lower 6-year Disease Free Survival (DFS) (16.0 vs 25 months) (p&gt;0.05) and lower 6- year Overall survival (OS) (37.9 vs 49.7 months (controls) (p&lt;0.001) than HIV (-) patients. Conclusions: In multivariate analysis ECOG ≥ 2, OI and no response to chemotherapy were adverse prognostic factors for OS in ARL. ORC is lower in ARL, though similar DFS of patients with malignant lymphoma HIV(+) vs HIV(-). [Table: see text]