Clinical significance of rituximab infusion-related reaction in diffuse large B-cell lymphoma patients receiving R-CHOP.

BACKGROUND/AIMS: This study was to evaluate the clinical significance of infusion-related reaction (IRR) of rituximab in diffuse large B-cell lymphoma (DLBCL) patients who received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) as a first-line chemotherapy. METHODS: The medical records of 326 patients diagnosed with DLBCL were re trospectively analyzed. Both doctor's progress records and nursing records were reviewed. IRR was graded according to the National Cancer Institute Common Terminology Criteria. RESULTS: IRR was not associated with overall survival (OS) or progression-free survival (PFS) of DLBCL patients as compared to those who did not have IRR (OS: median 78.0 months vs. 69.0 months, p = 0.700; PFS: median 65.4 months vs. 64.0 months, p = 0.901). IRR grade did not affect OS or PFS. B symptoms was independently associated with IRR (hazard ratio [HR], 1.850; 95% confidence interval [CI], 1.041 to 3.290; p = 0.036). Further, bone marrow involvement was independently associated with re-IRR (HR, 4.904; 95% CI, 0.767 to 3.118; p = 0.029). CONCLUSION: Our study shows that IRR of rituximab is not associated with OS or PFS of DLBCL patients who received R-CHOP. Furthermore, our study suggests a need for more careful observation for IRR in patients with B symptoms or bone marrow involvement.

One dimensional building blocks for molecular separation: laminated graphitic nanoribbons.

Herein, a new carbon-based graphitic membrane composed of laminated graphitic nanoribbons with a nanometer-scale width and micrometer-scale length, the graphitic nanoribbon membrane, is reported. Compared to the existing graphitic membranes, such as those composed of graphene oxide and carbon nanotubes, the developed membrane exhibits several unique characteristics in pressure-driven systems. First, the short diffusion length through its interlayer and the free volume of its stacked nanoribbons result in high solvent flux regardless of solvent polarity (water: 25-250 L m-2 h-1 bar-1; toluene: ∼975 L m-2 h-1 bar-1; hexane: ∼240 L m-2 h-1 bar-1). The flux value for water is one order of magnitude higher, while that for nonpolar organic solvents is two to three orders of magnitude greater than the corresponding flux values obtained through commercially available nanofiltration membranes. Second, the membrane exhibits good separation performance, particularly with organic dye molecules (∼100%) and trivalent ions (∼60%), maintaining high solvent flux during extended filtration. Finally, the membrane exhibits high stability in various fluids, e.g., 1 M HCl solution, 1 M NaOH solution, toluene, ethanol, and water, as well as under hydraulic pressures of up to 50 bar. Electron microscopy observation and simulation results suggest that such distinctive features of the membrane are related to the entangled thin multilayers of the graphitic nanoribbons, which possibly originate from the high aspect ratio and narrow width of the nanoribbons.

Skeletal muscle depletion predicts survival of patients with advanced biliary tract cancer undergoing palliative chemotherapy.

BACKGROUND: No prior study has investigated the dynamics of body weight with body muscle mass as a prognostic factor in advanced biliary tract cancer (BTC) patients undergoing palliative chemotherapy. We investigated whether low skeletal muscle mass affects survival in patients with BTC, with a co-analysis of body weight loss and body mass index (BMI). RESULTS: By multivariate analysis, low skeletal muscle mass at diagnosis and decreased SMI during chemotherapy (p = 0.008 and p < 0.001, respectively) were poor prognostic factors for overall survival (OS). Subgroup analysis revealed that low skeletal muscle mass patients who were overweight or obese (BMI ≥ 25 kg/m2) showed worse OS (p < 0.001). Additionally, patients with both decreased BMI and SMI during chemotherapy had worse OS (p < 0.001). Furthermore, patients with decreased SMI had shorter survival regardless of change in BMI. However, for patients with SMI maintained during chemotherapy, decreased BMI had no effect on survival (p = 0.576). MATERIALS AND METHODS: We consecutively enrolled 524 patients with advanced BTC who received palliative chemotherapy between 2003 and 2013. Total muscle cross-sectional area (cm2) at the L3 level assessed by computed tomography was analyzed. We defined low skeletal muscle mass as a skeletal muscle index (SMI) < 48.5 cm2/m2 (men) and < 39.5 cm2/m2 (women) using ROC curves. CONCLUSIONS: Low skeletal muscle mass, obesity and muscle depletion during palliative chemotherapy are meaningful prognostic factors in advanced BTC. Considering muscle depletion with weight change could help to more accurately predict prognoses of patients with BTC.

Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and their dynamic changes during chemotherapy is useful to predict a more accurate prognosis of advanced biliary tract cancer.

BACKGROUND AND PURPOSE: Systemic inflammation is known to promote carcinogenesis in biliary tract cancer (BTC). Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are indicative of systemic inflammation. We evaluated the clinical significance of systemic inflammation measured by NLR and PLR in patients with advanced BTC. Additionally, we also co-analyzed the dynamics of NLR and PLR during chemotherapy. METHODS: We reviewed 450 patients with unresectable BTC receiving palliative chemotherapy. NLR and PLR were obtained before initiation of palliative chemotherapy. Changes in NLR, PLR were obtained by subtracting the initial value from the value obtained after progression of chemotherapy. RESULTS: Higher systemic inflammation status also had relation with a primary tumor site (p = 0.003) and higher levels of CEA (p = 0.038). The ROC cut-off values of NLR and PLR for predicting overall survival (OS) were 3.8 and 121, respectively. Patients with a high NLR or PLR had worse OS independently in multivariate analysis (6.90 vs. 9.80 months, p =0.002; 7.83 vs. 9.90 months, p =0.041, respectively). High NLR with increased NLR after chemotherapy is associated with worse OS and progression-free survival (PFS) (p < 0.001, p = 0.013 respectively). Results are similar for PLR. CONCLUSION: Systemic inflammation represented by NLR and PLR, predicts the OS of patients with advanced BTC who are receiving palliative chemotherapy. In addition, considering NLR/PLR with a dynamic change of NLR/PLR during chemotherapy might help to predict a more accurate prognosis.

Prognostic value and their clinical implication of 89-gene signature in glioma.

Gliomas are the most common and aggressive primary tumors in adults. The current approaches, such as histological classification and molecular genetics, have limitation in prediction of individual therapeutic outcomes due to heterogeneity within the tumor groups. Recent studies have proposed several gene signatures to predict glioma's prognosis. However, most of the gene expression profiling studies have been performed on relatively small number of patients and combined probes from diverse microarray chips. Here, we identified prognostic 89 common genes from diverse microarray chips. The 89-gene signature classified patients into good and bad prognostic groups which differed in the overall survival significantly, reflecting the biological characteristics and heterogeneity. The robustness and accuracy of the gene signature as an independent prognostic factor was validated in three microarray and one RNA-seq data sets independently. By incorporating into histological classification and molecular marker, the 89-gene signature could further stratify patients with 1p/19q co-deletion and IDH1 mutation. Additionally, subset analyses suggested that the 89-gene signature could predict patients who would benefit from adjuvant chemotherapy. Conclusively, we propose that the 89-gene signature would have an independent and accurate prognostic value for clinical use. This study also offers opportunities for novel targeted treatment of individual patients.

WITHDRAWN:Clinical efficacy of erlotinib, a salvage treatment for non-small cell lung cancer patients following gefitinib failure.

Ahead of Print article withdrawn by publisher.

Clinical efficacy of erlotinib, a salvage treatment for non-small cell lung cancer patients following gefitinib failure.

BACKGROUND/AIMS: The purpose of this study was to identify predictive factors for erlotinib treatment in non-small cell lung cancer (NSCLC) patients following gefitinib failure. METHODS: Forty-five patients with NSCLC who were treated with erlotinib following gefitinib failure at Seoul National University Hospital between August 2005 and November 2011 were enrolled. Epidermal growth factor receptor (EGFR) mutation status, pathologic findings and other clinical factors, including response to tyrosine kinase inhibitors (TKIs) and progression-free survival (PFS), were evaluated. RESULTS: Of the 45 patients, 40 patients (88.8%) had adenocarcinoma. The following EGFR mutations were observed: five patients with a deletion of exon 19, six patients with an L858R mutation, three patients with wild-type EGFR, and 31 patients with unknown mutations. The response rate of erlotinib was 4.4%, and stable disease was 42.2%. The median PFS for erlotinib was 2.6 months (95% confidence interval, 1.4 to 3.7). Patients with a PFS ≥ 4 months during previous gefitinib treatment had a significantly longer PFS with erlotinib (3.3 months vs. 1.6 months, respectively; p < 0.01) than patients with PFS < 4 months with gefitinib. According to multivariate analyses, PFS ≥ 4 months for previous gefitinib treatment was significantly associated with prolonged PFS with erlotinib (p = 0.04). However, the response rate of gefitinib and treatment sequence were not associated with prolonged PFS with erlotinib (p = 0.28 and p = 0.67, respectively). CONCLUSIONS: Following rechallenge with the EGFR TKI erlotinib following gefitinib failure, patients who showed prolonged PFS with gefitinib benefit from erlotinib. However, further prospective studies are needed to confirm these findings.

CRC-113 gene expression signature for predicting prognosis in patients with colorectal cancer.

Colorectal cancer (CRC) is the third leading cause of global cancer mortality. Recent studies have proposed several gene signatures to predict CRC prognosis, but none of those have proven reliable for predicting prognosis in clinical practice yet due to poor reproducibility and molecular heterogeneity. Here, we have established a prognostic signature of 113 probe sets (CRC-113) that include potential biomarkers and reflect the biological and clinical characteristics. Robustness and accuracy were significantly validated in external data sets from 19 centers in five countries. In multivariate analysis, CRC-113 gene signature showed a stronger prognostic value for survival and disease recurrence in CRC patients than current clinicopathological risk factors and molecular alterations. We also demonstrated that the CRC-113 gene signature reflected both genetic and epigenetic molecular heterogeneity in CRC patients. Furthermore, incorporation of the CRC-113 gene signature into a clinical context and molecular markers further refined the selection of the CRC patients who might benefit from postoperative chemotherapy. Conclusively, CRC-113 gene signature provides new possibilities for improving prognostic models and personalized therapeutic strategies.

Salvage Treatment with Intracerebrospinal Fluid Thiotepa in Patients with Leptomeningeal Metastasis After Failure of Methotrexate-based Treatment.

AIM: To evaluate the efficacy of intracerebrospinal fluid (intra-CSF) thiotepa in patients with leptomeningeal metastasis (LM) after failure of a methotrexate-based treatment. PATIENTS AND METHODS: We retrospectively reviewed the medical records of patients with LM who received 10 mg of intra-CSF thiotepa twice a week. RESULTS: Out of 40 patients, 25 were females (63%), and 31 (78%) had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2. Fourteen out of the 30 evaluable patients (47%) had a cytological response to intra-CSF thiotepa. The median overall survival (OS) after treatment with thiotepa was 19.4 weeks (95% confidence interval (CI)=15.3-23.5). Grade 3 toxicities were thrombocytopenia (N=2), bacterial meningitis (N=2), and pneumonia (N=1). According to a multivariate analysis, an ECOG PS ≥2 (hazard ratio (HR)=5.11, 95% CI=1.39-18.80, p=0.014), clinical improvement (HR=0.09, 95% CI=0.03-0.29, p<0.001), and radiation for LM after intra-CSF thiotepa (HR=0.33, 95% CI=0.11-0.97, p=0.043) were independently associated with survival. CONCLUSION: Intra-CSF thiotepa seems to be a meaningful salvage treatment for patients with LM whose disease progresses after a methotrexate-based treatment.

Metabolic Characteristics of Advanced Biliary Tract Cancer Using 18F-Fluorodeoxyglucose Positron Emission Tomography and Their Clinical Implications.

BACKGROUND: In advanced biliary tract cancer (BTC), the metabolic landscape has not been evaluated by (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) yet. Furthermore, reports of the clinical implications of these metabolic features are limited. We aimed to evaluate the metabolic features and their clinical relevance in advanced BTC using (18)F-FDG PET. PATIENTS AND METHODS: We consecutively enrolled patients with advanced BTC who underwent (18)F-FDG PET prior to palliative chemotherapy between 2003 and 2013. We evaluated the findings of PET, such as SUV(max), the number of lesions and organs with FDG uptake, pathologic findings, and clinical outcomes. RESULTS: A total of 106 patients were enrolled: (53 intrahepatic cholangiocarcinoma [ICC], 7 extrahepatic BTC, 30 gallbladder cancer [GB Ca], and 16 ampulla of Vater cancer [AoV Ca]). The median SUV(max) differed according to the primary origin (ICC, 9.10; extrahepatic BTC, 5.90; GB Ca, 9.10; and AoV Ca, 6.37; p = .008) and histologic differentiation (well differentiated, 4.95; moderately differentiated, 6.60; poorly differentiated, 14.50; p = .004). Patients in the high metabolic group (SUV(max) of ≥7.5) had more poorly differentiated histology and more organs and lesions with FDG uptake than did those in the low metabolic group (SUV(max) of <7.5). The low metabolic group had a significantly longer OS (11.4 vs. 7.4 months, p = .007) and PFS (6.6 vs. 4.3 months, p = .024) than high metabolic group. In multivariate analysis, SUV(max) was a significant prognostic factor for overall survival (OS; p = .047) and progression-free survival (PFS; p = .039). CONCLUSION: Metabolic characteristics of advanced BTC differ according to primary origin and histology. These metabolic features could be prognostic factors for OS and PFS in advanced BTC.