scholarly journals Low CCL19 Expression Is Associated With Adverse Clinical Outcomes For Patients With Advanced Stage Follicular Lymphoma

Author(s):  
Yu Zhou ◽  
Shasha Wang ◽  
Yunxia Tao ◽  
Haizhu Chen ◽  
Yan Qin ◽  
...  

Abstract Background: This study aimed to explore the interactions and relationships of genes and recognize the hub genes associated with prognosis in follicular lymphoma (FL) treated with first-line rituximab combined with chemotherapy.Method: RNA sequencing data of dataset GSE65135 (n=24) were included in differentially expressed genes (DEGs) analysis. Weighted gene co-expression network analysis (WGCNA) was applied for exploring the coexpression network and identifying hub genes. Validation of hub genes expression and prognosis were applied in dataset GSE119214 (n=137) and patient cohort of Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (n=32), respectively, by analyzing RNAseq expression data and serum protein concentration quantified by ELISA. CIBERSORT was applied for tumor-infiltrating immune cells (TIICs) subset analysis. Results: A total of 3260 DEGs were obtained, with 1861 genes upregulated and 1399 genes downregulated. Using WGCNA and Cytoscape analysis, eight hub genes, PLA2G2D, MMP9, PTGDS, CCL19, NFIB, YAP1, RGL1, and TIMP3 were identified. Kaplan-Meier analysis and multivariate COX regression analysis indicated that CCL19 independently associated with overall survival (OS) for FL patients treated with rituximab and chemotherapy (HR = 0.47, 95%CI [0.25-0.86], p = 0.014). Higher Serum CCL19 concentration was associated with longer progression-free survival (PFS, p=0.014) and OS (p=0.039). TIICs subset analysis showed that CCL19 expression had a positive correlation with monocytes and macrophages M1, and a negative correlation with naïve B cells and plasma cells. Conclusion: CCL19 expression was associated with survival outcomes and might be a potential prognostic biomarker for FL treated with first-line immunochemotherapy.

2021 ◽  
Author(s):  
Yu Zhou ◽  
Shasha Wang ◽  
Yunxia Tao ◽  
Haizhu Chen ◽  
Yan Qin ◽  
...  

Abstract Background: This study aimed to recognize the hub genes associated with prognosis in follicular lymphoma (FL) treated with first-line rituximab combined with chemotherapy.Method: RNA sequencing data of dataset GSE65135 (n=24) were included in differentially expressed genes (DEGs) analysis. Weighted gene co-expression network analysis (WGCNA) was applied for exploring the coexpression network and identifying hub genes. Validation of hub genes expression and prognosis were applied in dataset GSE119214 (n=137) and independent patient cohort from Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (n=32), respectively, by analyzing RNAseq expression data and serum protein concentration quantified by ELISA. The Gene Set Enrichment Analysis (GSEA), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments analysis were performed. CIBERSORT was applied for tumor-infiltrating immune cells (TIICs) subset analysis. Results: A total of 3260 DEGs were obtained, with 1861 genes upregulated and 1399 genes downregulated. Using WGCNA, eight hub genes, PLA2G2D, MMP9, PTGDS, CCL19, NFIB, YAP1, RGL1, and TIMP3 were identified. Kaplan-Meier analysis and multivariate COX regression analysis indicated that CCL19 independently associated with overall survival (OS) for FL patients treated with rituximab and chemotherapy (HR = 0.47, 95%CI [0.25-0.86], p = 0.014). Higher serum CCL19 concentration was associated with longer progression-free survival (PFS, p=0.014) and OS (p=0.039). TIICs subset analysis showed that CCL19 expression had a positive correlation with monocytes and macrophages M1, and a negative correlation with naïve B cells and plasma cells. Conclusion: CCL19 expression was associated with survival outcomes and might be a potential prognostic biomarker for FL treated with first-line chemoimmunotherapy.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yu Zhou ◽  
Shasha Wang ◽  
Yunxia Tao ◽  
Haizhu Chen ◽  
Yan Qin ◽  
...  

Abstract Background This study aimed to recognize the hub genes associated with prognosis in follicular lymphoma (FL) treated with first-line rituximab combined with chemotherapy. Method RNA sequencing data of dataset GSE65135 (n = 24) were included in differentially expressed genes (DEGs) analysis. Weighted gene co-expression network analysis (WGCNA) was applied for exploring the coexpression network and identifying hub genes. Validation of hub genes expression and prognosis were applied in dataset GSE119214 (n = 137) and independent patient cohort from Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (n = 32), respectively, by analyzing RNAseq expression data and serum protein concentration quantified by ELISA. The Gene Set Enrichment Analysis (GSEA), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments analysis were performed. CIBERSORT was applied for tumor-infiltrating immune cells (TIICs) subset analysis. Results A total of 3260 DEGs were obtained, with 1861 genes upregulated and 1399 genes downregulated. Using WGCNA, eight hub genes, PLA2G2D, MMP9, PTGDS, CCL19, NFIB, YAP1, RGL1, and TIMP3 were identified. Kaplan–Meier analysis and multivariate COX regression analysis indicated that CCL19 independently associated with overall survival (OS) for FL patients treated with rituximab and chemotherapy (HR = 0.47, 95% CI [0.25–0.86], p = 0.014). Higher serum CCL19 concentration was associated with longer progression-free survival (PFS, p = 0.014) and OS (p = 0.039). TIICs subset analysis showed that CCL19 expression had a positive correlation with monocytes and macrophages M1, and a negative correlation with naïve B cells and plasma cells. Conclusion CCL19 expression was associated with survival outcomes and might be a potential prognostic biomarker for FL treated with first-line chemoimmunotherapy.


Author(s):  
Sirui Ma ◽  
Soumon Rudra ◽  
Jian L Campian ◽  
Milan G Chheda ◽  
Tanner M Johanns ◽  
...  

Abstract Background Optimal management for recurrent IDH-mutant glioma after radiation therapy (RT) is not well-defined. This study assesses practice patterns for managing recurrent IDH-mutant astrocytoma (Astro) and 1p/19q codeleted oligodendroglioma (Oligo) after RT and surveys their clinical outcomes after different salvage approaches. Methods Ninety-four recurrent Astro or Oligo patients after RT who received salvage systemic therapy (SST) between 2001 and 2019 at a tertiary cancer center were retrospectively analyzed. SST was defined as either alkylating chemotherapy (AC) or non-alkylating therapy (non-AC). Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method from the start of SST. Multivariable analysis (MVA) was conducted using Cox regression analysis. Results Recurrent Oligo (n=35) had significantly higher PFS (median: 3.1 vs 0.8 years, respectively, P = 0.002) and OS (median: 6.3 vs 1.5 years, respectively, P < 0.001) than Astro (n=59). Overall, 90% of recurrences were local. Eight-three percent received AC as the first-line SST; 50% received salvage surgery before SST; approximately 50% with local failure >2 years after prior RT received reirradiation. On MVA, non-AC was associated with worse OS for both Oligo and Astro; salvage surgery was associated with improved PFS and OS for Astro; early reirradiation was associated with improved PFS for Astro. Conclusions Recurrent radiation-relapsed IDH-mutant gliomas represent a heterogeneous group with variable treatment approaches. Surgery, AC, and reirradiation remain the mainstay of salvage options for retreatment.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1781-1781 ◽  
Author(s):  
Adam Vilmar ◽  
Bente Arboe ◽  
Par Josefsson ◽  
Christian Poulsen ◽  
Jacob Haaber Christensen ◽  
...  

Abstract Introduction Patients with follicular lymphomas (FL) often follow an indolent disease course initiated with the wait-and-watch approach. Chemotherapy, including rituximab (R), is inevitably required in most patients though. R-maintenance is indicated for patients achieving a partial or complete remission based results from randomized clinical trials and confirmed by meta-analyses demonstrating a prolonged progression free survival. A benefit in overall survival (OS), however, has yet to be established in the first line setting. Patients and methods We completed a retrospective analysis in patients extracted from the Danish National Lymphoma Register. Eligible patient data included histopathological confirmation of FL diagnosed in the period 2000-2014 who received R-Chemotherapy as first line treatment and surviving a minimum 1 year after treatment initiation. A Cox regression model was performed, adjusted for age, gender, stage, response rates and treatment period (pre-maintenance era (year 2000-2010) vs. maintenance era (year 2011-2014)) with hazard ratio (HR) of OS as the primary endpoint. All patients were followed until June 2016. Results 1037 patients were extracted from the register. 481 patients received R-maintenance (RM-group) and 556 patients did not. The median age was 62 (26-90), 526 (51%) were male, LDH was elevated in 325 (31%) and 436 (42%) had a high FLIPI index. The median follow-up time was 6.3 years. The five year OS for all patients was 86%. A significant change in the chemotherapy regimens was observed between the two groups, since Bendamustine was more frequently used in the maintenance group. A significant lower HR was observed in the RM group with a HR of 0.63 (95% CI 0.44 - 0.88, P = 0.008). Furthermore, gender proved of significance, with a HR for men of 1.78 (95% CI 1.32-2.40, P < 0.001). Conclusions Rituximab maintenance treatment following first line immunochemotherapy in patients with follicular lymphoma improved survival in a large population based cohort of patients and consolidates this strategy as part of the standard of care in this patient group. Disclosures No relevant conflicts of interest to declare.


Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 815
Author(s):  
Snezhanna O. Gening ◽  
Tatyana V. Abakumova ◽  
Dina U. Gafurbaeva ◽  
Albert A. Rizvanov ◽  
Inna I. Antoneeva ◽  
...  

Stem properties allow circulating tumor cells (CTCs) to survive in the bloodstream and initiate cancer progression. We aimed to assess the numbers of stem-like CTCs in patients with ovarian cancer (OC) before treatment and during first-line chemotherapy (CT). Flow cytometry was performed (Cytoflex S (Beckman Coulter, CA, USA)) using antibodies against CD45; epithelial markers EpCAM and cytokeratin (CK) 8,18; mesenchymal vimentin (vim); and stem-like CD44, CD133 and ALDH. This study included 38 stage I–IV OC patients (median age 66 (Q1–Q3 53–70)). The CK+vim- counts were higher (p = 0.012) and the CD133+ALDHhigh counts were lower (p = 0.010) before treatment in the neoadjuvant CT group than in the adjuvant group. The patients with ascites had more CK+vim- cells before treatment (p = 0.009) and less EpCAM-vim+ cells during treatment (p = 0.018) than the patients without ascites. All the CTC counts did not differ significantly in paired samples. Correlations were found between the CK-vim+ and CD133+ALDHhigh (r = 0.505, p = 0.027) and EpCAM-vim+ and ALDHhigh (r = 0.597, p = 0.004) cells before but not during treatment. Multivariate Cox regression analysis showed that progression-free survival was longer with the presence of surgical treatment (HR 0.06 95% CI 0.01–0.48, p = 0.009) and fewer CD133+ALDHveryhigh cells (HR 1.06 95% CI 1.02–1.12, p = 0.010). Thus, CD133+ALDH+ CTCs have the greatest prognostic potential in OC among the phenotypes studied.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4625-4625
Author(s):  
Salah-Eddin Al-Batran ◽  
Ralf Dieter Hofheinz ◽  
Alexander Reichart ◽  
Claudia Pauligk ◽  
Rudolf Schlag ◽  
...  

4625 Background: Gemcitabine and nab-paclitaxel (NPG) is standard first-line therapy for metastatic pancreatic cancer (mPC), but the pivotal study did not include quality of life (QoL) analyses. Methods: The QOLIXANE-PARAGON study started as a prospective, non-interventional, multicenter study conducted in Germany and transitioned into a permanent registry for pancreatic cancer patients (pts) considering all types of treatments. This report focuses on the pts enrolled into the QOLIXANE portion of the study. Pts were recruited from 95 German centers. QoL was prospectively measured via EORTC-C30 questionnaires (prior to and every month thereafter): therapy and efficacy parameters were prospectively collected. QoL and efficacy endpoints were analyzed in the intention-to-treat population (ITT). The primary endpoint was the rate of pts without deterioration of QoL/Global Health Score (QoL/GHS) at 3 months. Results: 600 pts were enrolled. Mean GHS/QoL score at baseline was low and was 46.2 (SD 22.8). Median progression-free survival was 5.85 months (95% CI, 5.23 to 6.25). Median overall survival (OS) was 8.91 months (95% CI, 7.89 to 10.19). The KM-analysis showed that 61% and 41% of pts had maintained QoL/GHS after 3 and 6 months, respectively. Median time to deterioration of QoL/GHS was 4.68 months (95% CI, 4.04 to 5.59). Mean QoL/GHS improved from 46.1 (SD 22.7) at baseline to 52.8 (SD 21.3) after 6 months. In the QoL response analysis, 34.6%, 37.4% and 28% of evaluable pts had improved, stable and worse QoL/GHS after 3 months, respectively. In the Cox regression analysis, GHS/QoL scores strongly predicted survival with a HR of 0.86 (p < 0.0001). Conclusions: QoliXane the largest study on QoL of mPC. It shows that time to deterioration of QoL is short but that a relevant group of mPC in first line have improved or maintained QoL after 3 and 6 months and that QoL is a predictor of pts outcome. Clinical trial information: NCT02691052 .


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16108-e16108
Author(s):  
Yuwen Zhou ◽  
Qiu Meng

e16108 Background: Cetuximab associated calcifications is a positive predictive factor in metastatic colorectal cancer (mCRC). In patients with glioblastoma, bevacizumab-induced calcifications are also related to a better prognosis. However, tumor calcifications are rarely recognized in mCRC patients treated with bevacizumab. This study was to investigate the correlation between clinical outcome and calcification in mCRC who received bevacizumab and chemotherapy as the first-line treatment. Methods: A single retrospective cohort study was conducted with all diagnosed mCRC cases who received bevacizumab and chemotherapy as the first-line therapy in our hospital from January 2016 to January 2019. Clinical variables were retrieved from medical records and tumor calcification were evaluated independently by radiologists on the basis of computed tomography scans. A univariate and multivariate COX regression analysis was performed to evaluate the association between calcification and outcome. Results: 159 patients with an average age of 59.0 years were included. Median follow-up was 29.6 months. Among all enrolled patients, 31 had tumor calcification [31/159 (19.5%)]. The median overall survival (OS) and progression-free survival (PFS) was significantly better in patients with calcification than those without calcification (28.0 vs. 24.9 months, p= 0.024; 12.0 vs. 10.0 months, p= 0.026). A higher objective response rate (61.3% vs. 50.0%) was also observed in calcification group. On multivariate analysis, tumor calcification was independently associated with OS (hazard ratio 1.799, 95% CI 1.002–3.230) and PFS (hazard ratio 1.609, 95% CI 1.013–2.557). Conclusions: Tumor calcification was independently associated with improved prognosis in colorectal cancer. It might be a potential prognostic marker.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1049-1049
Author(s):  
Mark Jesus Mendoza Magbanua ◽  
Oleksandr Oleksandr Savenkov ◽  
Erik Asmus ◽  
Karla V. Ballman ◽  
Janet H Scott ◽  
...  

1049 Background: CALGB 40503 randomized HR+ MBC postmenopausal pts to Let alone or Let+Bev as first-line therapy. Adding Bev to Let prolonged progression-free survival (PFS) but not overall survival (OS) (Dickler JCO 2016). We performed a correlative study to assess prognostic and predictive value of CTCs in this population. Methods: Blood was collected prior to initiation of treatment. CTCs were enumerated using US FDA-cleared CellSearch assay; samples with ≥5 CTCs per 7.5 mLs of blood were considered CTC-positive (CTC+). Correlation of CTCs with PFS and OS was assessed using Cox regression analysis. Median follow-up was 39 months (mo). Results: Of 343 pts treated, 294 had CTC data and were included in this analysis. Original study results that showed improved PFS (HR = 0.75; 95% CI: 0.59-0.96) but not OS (HR = 0.87; 95% CI: 0.65-1.18) in pts receiving Let+Bev compared to Let were recapitulated in this subset. In multivariable analysis, CTC+ pts (31%) had significantly reduced PFS (HR = 1.49; 95% CI: 1.12-1.97) and OS (HR = 2.08; 95% CI: 1.49-2.93) compared to CTC- pts. Moreover, CTC+ pts who did not receive Bev had worse PFS (HR = 2.31; 95% CI: 1.54-3.47) and OS (HR = 2.64; 95% CI: 1.59-4.40) (Table). CTC+ pts who received Bev had numerically longer median PFS (18.0 vs. 7.0 mo) and OS (33.6 vs. 27.1 mo) compared to CTC+ pts with no Bev; however, tests for interaction between CTC status and Bev (yes vs. no) were not statistically significant for PFS (p=0.70) or OS (p=0.84). Conclusions: CTCs were highly prognostic in this study involving addition of Bev to first-line Let in postmenopausal HR+ MBC. Further research to determine the potential predictive value of CTCs in the setting of both metastatic disease and early breast cancer is warranted. Support: U10CA180821, U10CA180882; Genentech; https://acknowledgments.alliancefound.org ; NCT00601900. Survival in HR+ MBC pts receiving Let or Let+Bev stratified by CTC status. Clinical trial information: NCT00601900. [Table: see text]


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Zhuo Wang ◽  
Liqun Zhang ◽  
Jingyan Wang ◽  
Yuanhe Wang ◽  
Qian Dong ◽  
...  

Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-related mortality worldwide. Inflammation and the nutritional status of patients with GC are important factors affecting the therapeutic effect and prognosis. Inflammatory and nutrition-related markers have been shown to be prognostic factors for patients with GC. However, few studies have investigated the relationship of the prealbumin-to-globulin ratio (PGR) with the prognosis of GC patients. The objective of the present study was to examine whether pretreatment PGR is related to the prognosis and chemotherapy outcomes of in-patients with advanced GC undergoing first-line chemotherapy. We retrospectively reviewed the data of 281 patients with unresectable GC from January 2013 to January 2018. The receiver operating characteristic curve analysis determined the cut-off values for the PGR. The relationship between the PGR and chemotherapy effectiveness was evaluated using the chi-square test. Kaplan-Meier’s method was used to plot progression-free survival (PFS) and overall survival (OS) curves, using multivariable Cox regression analysis to identify promising predictors of mortality. The cut-off value for the PGR was 7.21. The high-PGR (≥7.21) group had a higher disease control rate than that of the low-PGR group (93.66% vs. 78.42%, p<0.001). Kaplan-Meier’s analysis showed significantly higher median PFS (189 vs. 125 days, p<0.001) and OS (350 vs. 288 days, p<0.001) in the high-PGR group. The multivariate analyses revealed that a high PGR is an independent protective factor in patients with advanced GC, both in terms of PFS (hazard ratio [HR]: 0.672; 95% confidence interval [CI]: 0.527–0.857; p<0.001) and OS (HR: 0.675; 95% CI: 0.530–0.861; p=0.002). In conclusion, the prechemotherapy PGR can accurately predict the chemotherapy outcome, PFS, and OS of patients with advanced GC. Therefore, medical practitioners can utilize the PGR as a novel dependable prognostic tool to weigh the prognosis of patients with GC.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kiyoharu Fukushima ◽  
Seigo Kitada ◽  
Sho Komukai ◽  
Tomoki Kuge ◽  
Takanori Matsuki ◽  
...  

AbstractThe combination of rifamycin (RFP), ethambutol (EB), and macrolides is currently the standard regimen for treatment of Mycobacterium avium complex pulmonary disease (MAC-PD). However, poor adherence to the standardized regimens recommended by current guidelines have been reported. We undertook a single-centred retrospective cohort study to evaluate the long-term outcomes in 295 patients with MAC-PD following first line treatment with standard (RFP, EB, clarithromycin [CAM]) or alternative (EB and CAM with or without fluoroquinolones (FQs) or RFP, CAM, and FQs) regimens. In this cohort, 80.7% were treated with standard regimens and 19.3% were treated with alternative regimens. After heterogeneity was statistically corrected using propensity scores, outcomes were superior in patients treated with standard regimens. Furthermore, alternative regimens were significantly and independently associated with sputum non-conversion, treatment failure and emergence of CAM resistance. Multivariate cox regression analysis revealed that older age, male, old tuberculosis, diabetes mellitus, higher C-reactive protein, and cavity were positively associated with mortality, while higher body mass index and M. avium infection were negatively associated with mortality. These data suggest that, although different combination regimens are not associated with mortality, first line administration of a standard RFP + EB + macrolide regimen offers the best chance of preventing disease progression in MAC-PD patients.


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