Prognostic Factor For Longer Survival Research Articles

The Clinical Role of Adjuvant Chemotherapy after Sublobar Resection for Non-Small-Cell Lung Cancer ≤ 20 mm with Lymph Node Metastases: A Propensity-Matched Analysis of the National Cancer Database.

Sublobar resection is a standard surgical procedure for small-sized non-small-cell lung cancer (NSCLC). However, the clinical role of adjuvant chemotherapy for small-sized NSCLC with pathological lymph node (LN) metastasis after sublobar resection is unknown. The National Cancer Database was queried for NSCLC patients between 2004 and 2018. Eligibility included sublobar resection with pathological LN metastasis, R0 resection, Charlson comorbidity score = 0, clinical stage T1a-b, and tumor size ≤ 20 mm. The Kaplan-Meier method with a log-rank test and multivariable Cox proportional hazards analyses were used for assessing survival. The samples were evaluated before and after propensity score matching (PSM) with respect to age, sex, histologic type, and pathological LN status. Of 810 patients who met the eligibility criteria, 567 (70.0%) underwent adjuvant chemotherapy. After PSM, patients with adjuvant chemotherapy had a significantly longer survival than those without (median survival: 64.3 vs. 34.0 months, hazard ratio for death: 0.61, p < 0.0001). Multivariate analyses after PSM showed that younger age (p = 0.0206), female (p = 0.0005), and adjuvant chemotherapy (p < 0.0001) were independent prognostic factors for longer survival. Adjuvant chemotherapy has a prognostic impact in patients with small-sized NSCLC and pathological lymph node metastasis who undergo sublobar resection.

Neoadjuvant chemotherapy is associated with suppression of the B cell-centered immune landscape in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at advanced stages and associated with early distant metastasis and poor survival. Besides clinical factors, the tumor microenvironment (TME) emerged as a crucial determinant of patient survival and therapy response in many tumors, including PDAC. Thus, the presence of tumor-infiltrating lymphocytes and the formation of tertiary lymphoid structures (TLS) is associated with longer survival in PDAC. Although neoadjuvant therapy (NeoTx) has improved the management of locally advanced tumors, detailed insight into its effect on various TME components is limited. While a remodeling towards a proinflammatory state was reported for PDAC-infiltrating T cells, the effect of NeoTx on B cell subsets, including plasma cells, and TLS formation is widely unclear. We thus investigated the frequency, composition, and spatial distribution of PDAC-infiltrating B cells in primary resected (PR) versus neoadjuvant-treated patients using a novel multiplex immunohistochemistry panel. The NeoTx group displayed significantly lower frequencies of pan B cells, GC B cells, plasmablasts, and plasma cells, accompanied by a reduced abundance of TLS. This finding was supported by bulk RNA-sequencing analysis of an independent fresh frozen tissue cohort, which revealed that major B cell pathways were downregulated in the NeoTx group. We further observed that plasma cells frequently formed aggregates that localized close to TLS and that TLS+ patients displayed significantly higher plasma cell frequencies compared to TLS- patients in the PR group. Additionally, high densities of CD20+ intratumoral B cells were significantly associated with longer overall survival in the PR group. While CD20+ B cells held no prognostic value for NeoTx patients, an increased frequency of proliferating CD20+Ki67+ B cells emerged as an independent prognostic factor for longer survival in the NeoTx group. These results indicate that NeoTx differentially affects PDAC-infiltrating immune cells and may have detrimental effects on the existing B cell landscape and the formation of TLS. Gaining further insight into the underlying molecular mechanisms is crucial to overcome the intrinsic immunotherapy resistance of PDAC and develop novel strategies to improve the long-term outcome of PDAC patients.

Survival after reoperation for recurrent glioblastoma multiforme: A prospective study

PurposeGlioblastoma multiforme (GBM) is the most common malignant brain tumor. Moreover, GBM recurs in nearly all patients. Although a standard STUPP protocol has been widely used for newly diagnosed GBM, no standard regimen has been established for recurrent patients. Here we evaluated the clinical value of recurrent GBM reoperation by comparing overall survival and quality of life (QoL) in patients with recurrent GBM undergoing repeat surgery or conservative treatment. MethodsThis was a prospective study of 165 patients with GBM receiving first operations for their disease between 2011 and 2013 at two tertiary neurosurgery centers in Poland. Thirty-five eligible patients were re-operated for recurrence (the study group), and 35 patients were selected as the control group using propensity score matching. A model was created to determine advantageous prognostic factors for longer survival of patients qualifying for reoperation using stepwise linear regression. ResultsThe mean overall survival of patients undergoing repeat surgery was 528 days compared to 297 days in patients who did not undergo repeat surgery. Reoperation did not result in a significant deterioration in performance status as measured by the Karnofsky Performance Scale. Older age, the presence of symptoms of increased intracranial pressure, and a shorter period between initial operation and reoperation were independent predictors of a worse outcome. ConclusionIn selected patients, reoperation for recurrent GBM prolongs survival with no significant deteriorations in performance status.

1113P Mortality prediction in real world advanced melanoma patients treated by anti-PD1 within MelBase, a French multicentric prospective cohort

Anti-PD1 (Nivolumab, Pembrolizumab, APD) treatment (monotherapy or combination) efficacy is largely documented in advanced melanoma (AM) patients, as well as classical prognostic factors for longer survival. This study investigates 1- and 2-years mortality prediction in real world AM patients (rwAM), according to the most associated prognostic factors.

Clinical significance of topoisomerase-II expression in patients with advanced non-small cell lung cancer treated with amrubicin.

BackgroundAmrubicin chemotherapy is a treatment option for patients with non‐small cell lung cancer (NSCLC) after third‐line treatment in Japan. Although topoisomerase‐II (Topo‐II), a target of amrubicin, has been reported to be a prognostic or predictive marker for chemosensitivity and clinical outcomes in various types of malignancies, its effects in the Japanese population remain unknown.MethodsData regarding 44 patients with advanced NSCLC treated with amrubicin between April 2004 and May 2014 were retrospectively analyzed. We evaluated the expression levels of Topo‐II by immunohistochemical staining of tumor specimens obtained via biopsy or surgical resection.ResultsThe majority of enrolled patients were men (68%) with a median age of 67 (range, 43–78) years. The most common histological type was adenocarcinoma (70%). High Topo‐II expression was observed in 13 (30%) of the 44 patients. The median progression‐free survival and overall survival (OS) durations were 1.8 and 8.8 months, respectively. While there was no significant association between Topo‐II expression and progression‐free survival, patients with low Topo‐II expression had significantly longer OS than did those with high Topo‐II expression. Good performance status and low expression of Topo‐II were all significantly associated with a favorable OS.ConclusionLow expression of Topo‐II was identified as an independent prognostic factor for longer survival in patients with NSCLC receiving amrubicin, a Topo‐II inhibitor.Key pointsSignificant findings of the study The median progression‐free survival and overall survival (OS) durations were 1.8 and 8.8 months, respectively.While there was no significant association between Topo‐II expression and progression‐free survival, patients with low Topo‐II expression had significantly longer OS than did those with high Topo‐II expression.Good performance status and low expression of Topo‐II were all significantly associated with a favorable OS. What this study adds This study is the first to assess the effects of topoisomerase‐II (Topo‐II), a target of amrubicin, as a prognostic or predictive marker for chemosensitivity and clinical outcomes in the Japanese population.

ACT-10 TREATMENT FOR GLIOBLASTOMA RECURRED AFTER CONCOMITANT CHEMORADIATION THERAPY WITH TEMOZOLOMIDE AND THEIR PROGNOSIS

There are few data about treatment for glioblastoma recurred after concomitant chemoradiation therapy with temozolomide (TMZ). We retrospectively examined treatment and prognosis of recurred glioblastoma patients who registered Kansai molecular diagnosis network for central nervous system tumors, and whose clinical information were available. One hundred and fifty-seven patients that were clinically diagnosed as recurrence between November 2007 and April 2019 were included. Their median age at primary diagnosis was 52 years old and median KPS was 80%. Proportion of methylated MGMT promoter was 43.3% (65 patients), and mutated IDH was 5.4% (8 patients). Median overall survival after recurrence (mSAR) was 8.2 months. One hundred and sixteen patients (73.9%) were received any anticancer treatment and their mSAR was 10.5m. Combination of TMZ and bevacizumab (Bev) were most frequently used for 33 patients, followed by Bev monotherapy for 17 patients, surgery + TMZ + Bev for 15 patients, surgery + TMZ for 12 patients, and TMZ monotherapy for ten. Their mSAR were 8.0m, 7.5m, 10.5m, 13.0m, and 8.0m, respectively. Using univariate analysis, MGMT promoter methylation (p=0.0007), TMZ (p=0.00933), surgery (p=0.0126), re-radiation (p=0.0367), and surgery+TMZ+Bev (p=0.0493) significantly affected prognosis. By multivariate analysis, MGMT promoter methylation, TMZ, and re-radiation were statistically significant (p=0.000138, 0.00161, 0.00403, respectively). These data showed that relatively young patients with good performance status would receive anti-cancer treatment beyond progression and MGMT promoter methylation might be one of prognostic factor for longer survival. In this cohort, re-radiation was performed for few patients and nitrosourea such as nimustine was almost not used. Further study would be needed whether these treatments have any positive effect or not.

Arterial hyperenhancement of small intrahepatic cholangiocarcinomas correlates with microvessel counts and patient survival

BackgroundTo compare outcomes of patients with arterially hyperenhancing intrahepatic cholangiocarcinomas (ICC) and arterially hypoenhancing ICCs after partial hepatectomy in a cohort with an analysis of prognostic factors. MethodsFrom June 2009 to October 2011, a prospective cohort of 68 patients with single resectable ICCs (≤5 cm in diameter) underwent gadolinium contrast–enhanced dynamic-phase magnetic resonance imaging and were treated with partial hepatectomy. Patients were divided into those with arterially hyperenhancing ICCs (n = 28) or arterially hypoenhancing ICCs (n = 40). Clinic-radiologic-pathologic results and survival of these patients were compared and statistically analyzed. ResultsThe median overall survival (OS) time was significantly longer in the arterially hyperenhancing ICCs (56.8 vs. 37.0 months) (p = 0.044). At pathologic evaluation, arterially hyperenhancing ICCs showed significantly higher microvessel count (MVC) than arterially hypoenhancing ICCs (106.2 ± 47.5 vs. 46.9 ± 21.6/mm2, p = 0.001). Arterial enhancement of ICCs was found to be an independent prognostic factor for longer survival. ConclusionThe presence of arterially hyperenhancing ICCs is related to higher MVC and exhibit a better OS time than arterially hypoenhancing ICCs after partial hepatectomy.

Prognostic factors for survival in patients with metastatic malign melanoma treated with ipilimumab: Turkish Oncology Group study.

Studies in the last decade show survival improvement with checkpoint blocker therapy in patients with metastatic malign melanoma. Our purpose was to define the efficacy of ipilimumab according to the patient's baseline characteristics including absolute lymphocytes count. We collected the data of 97 patients with advanced malign melanoma treated with ipilimumab (3 mg/kg, q3w) retrospectively. Log-rank test was used to analyze the univariate effects of patient's characteristics (age, gender, metastatic sites, ECOG PS, type of melanoma, lactic dehydrogenase levels, anemia, lymphocytes (L), neutrophils (N), N/L ratio), c-kit and BRAF status. Survival analyses were estimated with Kaplan-Meier method. Cox regression analysis was used to assess the possible factors identified with log-rank test. The median age was 58, and 58% were male and 90% of patients had at least one prior systemic therapy. The median survival was 9.7 months for all patients; and the 12- and 24-month survival rates were 43% and 19%, respectively. Absolute lymphocytes count, lactic dehydrogenase level, bone metastasis, the number of metastatic sites, and RECIST response were significantly related to survival. After Cox regression analysis, RECIST response (complete or partial response), absolute lymphocytes count (more than 1500/mm3) and the number of metastatic sites (less than three sites) remained as significant independent prognostic factors for longer survival. Ipilimumab improved survival of patients with metastatic malign melanoma. However, patients with fewer metastatic sites and higher absolute lymphocytes count have a significantly better benefit. To determine if these markers could be used to direct patient therapy, further validation analysis is needed.

Liquid Biopsies Using Plasma Exosomal Nucleic Acids and Plasma Cell-Free DNA Compared with Clinical Outcomes of Patients with Advanced Cancers.

Purpose: Blood-based liquid biopsies offer easy access to genomic material for molecular diagnostics in cancer. Commonly used cell-free DNA (cfDNA) originates from dying cells. Exosomal nucleic acids (exoNAs) originate from living cells, which can better reflect underlying cancer biology.Experimental Design: Next-generation sequencing (NGS) was used to test exoNA, and droplet digital PCR (ddPCR) and BEAMing PCR were used to test cfDNA for BRAFV600, KRASG12/G13, and EGFRexon19del/L858R mutations in 43 patients with progressing advanced cancers. Results were compared with clinical testing of archival tumor tissue and clinical outcomes.Results: Forty-one patients had BRAF, KRAS, or EGFR mutations in tumor tissue. These mutations were detected by NGS in 95% of plasma exoNA samples, by ddPCR in 92% of cfDNA samples, and by BEAMing in 97% cfDNA samples. NGS of exoNA did not detect any mutations not present in tumor, whereas ddPCR and BEAMing detected one and two such mutations, respectively. Compared with patients with high exoNA mutation allelic frequency (MAF), patients with low MAF had longer median survival (11.8 vs. 5.9 months; P = 0.006) and time to treatment failure (7.4 vs. 2.3 months; P = 0.009). A low amount of exoNA was associated with partial response and stable disease ≥6 months (P = 0.006).Conclusions: NGS of plasma exoNA for common BRAF, KRAS, and EGFR mutations has high sensitivity compared with clinical testing of archival tumor and testing of plasma cfDNA. Low exoNA MAF is an independent prognostic factor for longer survival. Clin Cancer Res; 24(1); 181-8. ©2017 AACR.

Prognostic Factors in Glioblastoma: Is There a Role for Epilepsy?

The prognostic relevance of epilepsy at glioblastoma (GBMs) onset is still under debate. In this study, we analyzed the value of epilepsy and other prognostic factors on GBMs survival. We retrospectively analyzed the clinical, radiological, surgical and histological data in 139 GBMs. Seizures were the presenting symptoms in 50 patients out of 139 (35.9%). 123 patients (88%) were treated with craniotomy and tumor resection while 16 (12%) with biopsy. The median overall survival was 9.9 months from surgery. At univariable Cox regression, the factors that significantly improved survival were age less than 65 years (P = 0.0015), focal without impairment of consciousness seizures at presentation (P = 0.043), complete surgical resection (P < 0.001), pre-operative Karnofsky performance status (KPS) > 70 (P = 0.015), frontal location (P < 0.001), radiotherapy (XRT) plus concomitant and adjuvant TMZ (P < 0.001). A multivariable Cox regression showed that the complete surgical resection (P < 0.0001), age less than 65 years (P = 0.008), frontal location (P = 0.0001) and XRT adjuvant temozolomide (TMZ) (P < 0.0001) were independent factors on longer survival. In our series epilepsy at presentation is not an independent prognostic factor for longer survival in GBM patients. Only in the subgroup of patients with focal seizures without impairment of consciousness, epilepsy was associated with an increased significant overall survival at univariate analysis (P = 0.043). Main independent factors for relatively favorable GBMs outcome are complete tumor resection plus combined XRT-TMZ, frontal location and patient age below 65 years old.

Sodium Channel Subunit SCNN1B Suppresses Gastric Cancer Growth and Metastasis via GRP78 Degradation.

There remains a paucity of functional biomarkers in gastric cancer. Here, we report the identification of the sodium channel subunit SCNN1B as a candidate biomarker in gastric cancer. SCNN1B mRNA expression was silenced commonly by promoter hypermethylation in gastric cancer cell lines and primary tumor tissues. Tissue microarray analysis revealed that high expression of SCNN1B was an independent prognostic factor for longer survival in gastric cancer patients, especially those with late-stage disease. Functional studies demonstrated that SCNN1B overexpression was sufficient to suppress multiple features of cancer cell pathophysiology in vitro and in vivo Mechanistic investigations revealed that SCNN1B interacted with the endoplasmic reticulum chaperone, GRP78, and induced its degradation via polyubiquitination, triggering the unfolded protein response (UPR) via activation of PERK, ATF4, XBP1s, and C/EBP homologous protein and leading in turn to caspase-dependent apoptosis. Accordingly, SCNN1B sensitized gastric cancer cells to the UPR-inducing drug tunicamycin. GRP78 overexpression abolished the inhibitory effect of SCNN1B on cell growth and migration, whereas GRP78 silencing aggravated growth inhibition by SCNN1B. In summary, our results identify SCNN1B as a tumor-suppressive function that triggers UPR in gastric cancer cells, with implications for its potential clinical applications as a survival biomarker in gastric cancer patients. Cancer Res; 77(8); 1968-82. ©2017 AACR.

The Role of F-18 FDG PET/CT in Intrahepatic Cholangiocarcinoma.

The aim of this study was to evaluate the diagnostic and prognostic role of metabolic parameters of FDG PET/CT in patients with intrahepatic cholangiocarcinoma (ICC). From December 2008 to December 2013, 76 FDG PET/CT scans performed for initial staging of ICC in a single institution (57 male and 19 female; mean age 68 ± 9years) were retrospectively reviewed. Patients with history of other known malignancy were excluded. Detection rates of regional lymph node and distant metastasis by FDG PET/CT were analyzed in comparison with conventional imaging modalities such as CT or MRI. Metabolic parameters including maximum, peak and mean standardized uptake values (SUVmax, SUVpeak, SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), glucose corrected SUV (SUVgluc), and glucose corrected TLG (TLGgluc) were measured for the primary tumor. Cut-off values for the metabolic parameters were calculated by ROC curve analysis, and used to dichotomize the patient groups. The overall survival time (OS) was calculated and compared using the Cox proportional hazard regression analysis. The median duration of follow-up period was 5.4months (interquartile range: 1.45∼15.45). FDG PET/CT showed higher sensitivity than conventional imaging modalities in detection of regional node involvement (74.5% vs. 61.8%, p = 0.013). In six patients, distant metastasis was identified only by FDG PET/CT. The mean SUVmax, SUVpeak, SUVmean, MTV, and TLG for the primary tumor were 8.2 ± 3.1, 6.8 ± 2.5, 4.0 ± 0.8, 192.7 ± 360.5cm3, and 823.7 ± 1615.4, respectively. Patients with higher (≥7.3, HR: 4.280, p = 0.001), higher SUVpeak (≥6.5, HR: 2.333, p = 0.020), higher SUVmean (≥3.9, HR: 2.799, p = 0.004), higher SUVgluc (≥8.1, HR: 2.648, p = 0.012), and higher TLGgluc (≥431.6, HR: 2.186, p = 0.030) showed significantly shorter survival time. By multivariate study, operability was an independent prognostic factor for longer survival (HR: 4.113, p = 0.005). FDG PET/CT is an important diagnostic imaging tool in the nodal staging and detection of distant metastasis in ICC patients. Metabolic parameters may have a significant role as prognostic factors in patients with ICC.

Prognostic value of the autophagy markers LC3 and p62/SQSTM1 in early-stage non-small cell lung cancer.

Autophagy is a cellular degrading process that promotes tumor cell survival or cell death in cancer, depending on the progress of oncogenesis. Protein light chain 3 (LC3) and p62/SQSTM1 (p62) are associated with autophagosomal membranes that engulf cytoplasmic content for subsequent degradation. We studied LC3 and p62 expression using immunohistochemistry in a large cohort of 466 stage I/II non-small cell lung cancer (NSCLC) using a tissue microarray. We evaluated dot-like cytoplasmic expression of LC3 and dot-like, cytoplasmic and nuclear staining for p62 in relation to clinico-pathological parameters.LC3 expression correlated with all p62 patterns, as those correlated among each other (p < 0.001 each). There was no correlation with stage, age or gender. A combination of high LC3/high p62 dot-like staining (suggesting impaired autophagy) showed a trend for better outcome (p = 0.11). Interestingly, a combined low cytoplasmic/low nuclear p62 expression regardless of dot-like staining was an independent prognostic factor for longer survival (p = 0.006; HR=1.96), in addition to tumor stage (p = 0.004; HR=1.4).The autophagy markers LC3 and p62 are differentially expressed in NSCLC, pointing towards a biologically significant role. High LC3 levels seem to be linked to lower tumor aggressiveness, while high general p62 expression was significantly associated with aggressive tumor behavior.

Prognosis After Brain Metastasis from Differentiated Thyroid Carcinoma.

In patients with differentiated thyroid carcinoma (DTC), lung and bone metastasis sometimes occur. However, brain metastasis (BM) is extremely rare. Because most previous reports about BM from DTC included a relatively small number of cases, the clinical characteristics and outcomes of BM are still unclear. Between 1965 and 2013, among 961 patients who had died because of DTC, 24 patients were diagnosed with BM from DTC. One patient with BM from DTC is still alive. To identify the prognostic factors for longer survival after BM, the medical records of these 25 patients were retrospectively reviewed. The median age at BM diagnosis was 66 years. Typical symptoms associated with BM had appeared in 20 patients (80%). The Karnofsky Performance Status (KPS) was good (≥70) in 10 patients and poor (≤60) in 15 patients. Seven patients had a single intracranial lesion of BM, 6 patients had 2 or 3 lesions, and 9 patients had 4 or more. Eleven patients did not receive any treatment for BM, and 14 patients underwent surgical resection, radiation therapy, or both. One-year and 5-year disease-specific survival rates were 28 and 10.6%, respectively. Good KPS (≥70), small number of intracranial lesions (≤3), and treatment for BM were prognostic factors for long survival on univariate analysis (p < 0.05). On multivariate analysis, only treatment for BM was significant. Treatment of BM from DTC is indicated in patients who have a good KPS and fewer intracranial lesions, and some of them may achieve long survival.

Prognostic relevance of epilepsy at presentation in glioblastoma patients.

Epileptogenic glioblastomas are thought to convey a favorable prognosis, either due to early diagnosis or potential antitumor effects of antiepileptic drugs. We investigated the relationship between survival and epilepsy at presentation, early diagnosis, and antiepileptic drug therapy in glioblastoma patients. Multivariable Cox regression was applied to survival data of 647 consecutive patients diagnosed with de novo glioblastoma between 2005 and 2013 in order to investigate the association between epilepsy and survival in glioblastoma patients. In addition, we quantified the association between survival and valproic acid (VPA) treatment. Epilepsy correlated positively with survival (HR: 0.75 (95% CI: 0.61-0.92), P < .01). This effect is independent of age, sex, performance status, type of surgery, adjuvant therapy, tumor location, and tumor volume, suggesting that this positive correlation cannot be attributed solely to early diagnosis. For patients who presented with epilepsy, the use of the antiepileptic drug VPA did not associate with survival when compared with patients who did not receive VPA treatment. Epilepsy is an independent prognostic factor for longer survival in glioblastoma patients. This prognostic effect is not solely explained by early diagnosis, and survival is not associated with VPA treatment.

O10.09 * REDUCTION IN NEUTROPHIL-LYMPHOCYTE RATIO DURING INITIAL CONCURRENT CHEMORADIOTHERAPY IS PROGNOSTIC FOR SURVIVAL OF GLIOBLASTOMA PATIENTS

INTRODUCTION: Elevated baseline neutrophil-lymphocyte ratio (NLR) has been associated with poorer outcome in multiple tumour sites. In the context of glioblastoma (GBM), elevated NLR prior to any initial therapy, including surgery or corticosteroids, or prior to second surgery for recurrent disease predicted worse outcome. The aim of this retrospective cohort study was to assess if change in NLR during initial focal radiotherapy (RT) and concurrent temozolomide (TMZ) predicted outcome in newly diagnosed GBM patients. METHODS: A retrospective chart review was performed for patients treated concurrently with TMZ and RT, at our tertiary referral centre between Jan 2004 and Sept 2010, for histologically confirmed GBM. Age, baseline ECOG performance status (ECOG-PS) and extent of surgery were recorded. Baseline NLR, change in NLR, and time-weighted mean dexamethasone dose (TWMdex) were collected between 2 weeks prior to commencing RT and 10 weeks following the start of RT. Overall survival (OS) was calculated using Kaplan Meier method. Univariate (UVA) and multivariable (MVA) analyses using cox proportional hazard models evaluated variables associated with OS, accounting for colinearity of variables. RESULTS: There were 394 patients who met eligibility and were included in the final analysis. Median age was 54 (range 18-73). With median follow up of 15.2 months (range 1.6-134.6), OS was 66.4% (CI 61.4-70.7) and 31.1% (CI 26.5-35.8) at 1 and 2 years respectively. Median baseline dexamethasone dose was 8 mg (0-30 mg) and median TWMdex dose was 4.94 mg (0.0 -27.4 mg). On UVA, older age (HR 1.034, p 2 (HR 1.076, p < 0.001) were associated with shorter survival whereas baseline NLR below the median of 7.5 (HR 0.628, p < 0.0001) and decrease in NLR during treatment (HR 0.644, p < 0.0001) were associated with better survival. On MVA, decrease in NLR remained significantly prognostic for OS (HR 0.763, p = 0.02; CI 0.603 - 0.964) in addition to age (HR 1.032, p < 0.001; CI 1.018-1.045), TWMdex (HR 1.039, p = 0.002; CI 1.014-1.065) and ECOG-PS (HR 0.593, p = 0.008; CI 0.430-0.873). Although, baseline NLR was no longer statistically significant (HR 0.814, p = 0.09; CI 0.641 - 1.032), patients with low baseline NLR and further reduction in NLR during treatment had significantly longer survival (p < 0.0001). The association between change in NLR and change in dexamethasone dose over time was weak (r = 0.22). CONCLUSION: In patients with newly diagnosed glioblastoma, any reduction in neutrophil-lymphocyte ratio during initial concurrent chemoradiotherapy was an independent prognostic factor for longer survival, accounting for other prognostic factors including dexamethasone dose. Patients with low baseline NLR and further reduction in NLR during treatment had the best prognosis.

Low differentiated microvascular density and low expression of platelet‐derived growth factor‐BB (PDGF‐BB) predict distant metastasis and poor prognosis in clear cell renal cell carcinoma

To examine the prognostic significance of the expression of platelet-derived growth factor-BB (PDGF-BB) and differentiated microvascular density (MVD) in patients with clear cell renal cell carcinoma (ccRCC). We used the vascular marker cluster of differentiation 34 (CD34) to identify tumour blood vessels. The expression of PDGF-BB and CD34 was detected by immunohistochemistry (IHC) in tissue microarrays (TMAs) from 100 ccRCCs. Prognostic effects of individual parameters were calculated using Cox regression models and Harrell's concordance index (c-index). Higher grade and more advanced stage ccRCCs had significantly less PDGF-BB expression and differentiated MVD (P < 0.05). Higher PDGF-BB expression was an independent prognostic factor for longer survival, and moreover, the final model built by the addition of PDGF-BB expression improved the predictive accuracy for disease-free survival (c-index 0.707) compared with the clinicopathological-based model (c-index 0.695). PDGF-BB expression was positively associated with differentiated MVD assessed by Spearman correlation and factor analysis (r = 0.634, P < 0.001). PDGF-BB is as a novel and promising prognostic marker and antiangiogenic therapeutic target for the treatment of ccRCC.

Prognosis of hepatocellular carcinoma with portal vein tumor thrombus:assessment based on clinical and computer tomography characteristics.

Patients with hepatocellular carcinoma (HCC) complicated by portal vein tumor thrombus (PVTT) have an extremely poor prognosis. It is important to select adequate therapeutic options based on reliable prognostic factors using imaging studies and clinical data. Prognostic factors were analyzed in patients with HCC with PVTT in the first branch or main trunk of the portal vein. From 2000 to 2007, 107 consecutive patients with HCC with PVTT in the major portal vein were reviewed, and diagnostic images and clinical characteristics were retrospectively observed. Thirty-eight possible prognostic factors for survival were analyzed by the log-rank test and multivariate analysis using Cox's proportional hazards model. Median overall survival was 14 months following PVTT diagnosis. Survival rates at 6 months, 1, 2, and 3 years were 72.1%, 52.6%, 32.6%, and 29.6%, respectively. Independent prognostic factors for longer survival included:patient age < 65 years, Child-Pugh classification A/B, PVTT treatment, accumulation of Lipiodol in the PVTT after TACE, initial radical treatment for HCC, HCC located in a single lobe of the liver, and no invasion of HCC to the hepatic vein or bile duct. Survival was associated with liver function, tumor extension, and treatment for HCC and PVTT.

Aberrant expression of intelectin-1 in gastric cancer: its relationship with clinicopathological features and prognosis

Human intelectin-1 (ITLN-1) is a novel identified galactose-binding lectin that is expressed in the colonic goblet cells. Since gastric adenocarcinomas can arise through a process of intestinalization, we speculate that ITLN-1 may be aberrantly expressed in gastric cancer. This study was undertaken to examine the ITLN-1 expression in gastric cancer and correlate it with clinical outcomes. One hundred and ninety-six gastric cancer patients were evaluated for the ITLN-1 expression by immunohistochemistry. The ITLN-1 transcripts were measured by real-time quantitative PCR. ITLN-1 expression was absent in normal gastric mucosa, whereas areas of intestinal metaplasia revealed ITLN-1 immunoreactivity. One hundred and forty-two gastric cancer patients (72.4%) were positive for ITLN-1 expression. In a subtotal of 20 patients, ITLN-1 transcripts were significantly enhanced in gastric cancer tissues than in normal gastric mucosa (P<0.001). The expression rate of ITLN-1 was higher in intestinal-type carcinomas than in diffuse-type carcinomas (P=0.003). ITLN-1 positivity in gastric cancer was positively correlated with tumor differentiation (P=0.001) and CDX2 expression (P<0.001), and inversely correlated with depth of invasion (P=0.007), lymph node metastasis (P=0.001), distant metastasis (P=0.014), clinical stage (P=0.006), Ki-67 expression (P=0.001), and heparanase expression (P<0.001), without correlation with age, gender, tumor location, or tumor size. In univariate and multivariate analyses, ITLN-1 was an independent prognostic factor for longer survival of gastric cancer patients (P=0.001). The aberrant ITLN-1 expression in gastric cancer is correlated with clinicopathological features and may be a useful prognostic factor for predicting the outcomes of gastric cancer patients.

Early Significant Tumor Volume Reduction After Radiosurgery in Brain Metastases From Renal Cell Carcinoma Results in Long-Term Survival

To retrospectively evaluate survival of patients with brain metastasis from renal cell carcinoma (RCC) after radiosurgery. Between 1998 and 2010, 46 patients were treated with radiosurgery, and the total number of lesions was 99. The mean age was 58.9 years (range, 33-78 years). Twenty-six patients (56.5%) had a single brain metastasis. The mean tumor volume was 3.0 cm(3) (range, 0.01-35.1 cm(3)), and the mean marginal dose prescribed was 20.8 Gy (range, 12-25 Gy) at the 50% isodose line. A patient was classified into the good-response group when the sum of the volume of the brain metastases decreased to less than 75% of the original volume at a 1-month follow-up evaluation using MRI. As of December 28, 2010, 39 patients (84.8%) had died, and 7 (15.2%) survived. The overall median survival time was 10.0 ± 0.4 months (95% confidence interval, 9.1-10.8). After treatment, local tumor control was achieved in 72 (84.7%) of the 85 tumors assessed using MRI after radiosurgery. The good-response group survived significantly longer than the poor-response group (median survival times of 18.0 and 9.0 months, respectively; p = 0.025). In a multivariate analysis, classification in the good-response group was the only independent prognostic factor for longer survival (p = 0.037; hazard ratio = 0.447; 95% confidence interval, 0.209-0.953). Radiosurgery seems to be an effective treatment modality for patients with brain metastases from RCC. The early significant tumor volume reduction observed after radiosurgery seems to result in long-term survival in RCC patients with brain metastases.