Post-progression Survival Research Articles

Aberrant Expression of β-Catenin Correlates with Infiltrating Immune Cells and Prognosis in NSCLC.

Aims: β-catenin is a critical regulating factor of the Wnt pathway, which is closely linked to tumorigenesis, tumor growth, metastasis, and tumor immunity. Our study focused on exploring the relationship between β-catenin and clinicopathological features, prognosis, as well as infiltrating immune cells and immune scores, so as to illustrate its clinical significance in NSCLC. Materials and Methods: The β-catenin mRNA (CTNNB1) and protein expression data were downloaded from the UALCAN and the UCSC Xena website, respectively. All tumor-immune infiltrating cells’ data were downloaded from the TIMER platform and immune scores were downloaded from ESTIMATE website. The expression of β-catenin protein in our cohort was measured by immunohistochemistry. Results: β-catenin mRNA level was higher in lung adenocarcinoma (LUAD) compared to normal tissues (p < 0.001) and was related to overall survival (OS) (p < 0.001) and post-progression survival (PPS) (both p = 0.049) in LUAD. Aberrant β-catenin protein expression was higher in male and lung squamous cell carcinoma (LUSC) patients (both p = 0.001). Also, it was considered to be a prognosis factor independently (p = 0.034). In addition, β-catenin protein was negatively correlated with CD8+T cells (r = −0.128, p = 0.008), neutrophils (r = −0.198, p < 0.001), immune score (r = −0.109, p = 0.024), stromal score (r = −0.097, p = 0.045), and ESTIMATE score (r = −0.113, p = 0.020). Conclusions: Aberrant β-catenin protein expression was evidently higher in NSCLC and might serve as a biomarker for poor prognosis. Most importantly, β-catenin protein might play an important part in tumor immunity and the tumor microenvironment by inhibiting the infiltration of CD8+ T cells and neutrophils.

Significance of TEAD Family in Diagnosis, Prognosis and Immune Response for Ovarian Serous Carcinoma.

PurposeTo explore the molecular profiles of transcriptional enhanced associate domain (TEAD) family in ovarian serous carcinoma (OSC).MethodsIn this study, we use bioinformatics methods including GEPIA, GE-mini, Oncomine 3.0, Kaplan–Meier plotter, cBioPortal, WebGestalt, TIMER2.0 and DiseaseMeth2.0, and in vitro experimental RT-PCR to assess the expression profiles and prognostic significance of TEAD family in OSC.ResultsAccording to the bioinformatics analysis, TEAD family was abnormally expressed in OSC. In terms of prognosis, Kaplan–Meier plotter indicated that OSC patients with high level of TEAD4 showed poor overall survival (OS), progression-free survival (PFS) and post progression survival (PPS). TEAD family also had significantly diagnostic values for OSC patients. Tumor Immune Estimation Resource (TIMER) algorithm indicated that TEAD family was significantly associated with different types of infiltrating immune cells, including B cells, macrophages, dendritic cells, neutrophils, CD8+ T cells and CD4+ T cells. Gene set enrichment analysis of TEAD family-associated coexpression genes was further explored. In in vitro experiments, the RT-PCR results showed the upregulated TEAD2/4 in OSC tissues and cells (A2780 and TOV112D). Moreover, decreased expression of TEAD2 could induce the ferroptosis through increasing the ROS accumulation.ConclusionThus, TEAD family correlated with the diagnosis, prognosis and immune infiltration in OSC. These results could provide comprehensive understanding of TEAD family in the diagnosis and prognosis of OSC patients.

Prediction and prognostic significance of ALOX12B and PACSIN1 expression in gastric cancer by genome-wide RNA expression and methylation analysis.

Stomach adenocarcinoma (STAD) is one of the common gastrointestinal cancers, characterized by late discovery and metastasis. However, research of gene methylation and expression in gastric cancer (GC) metastasis has been quite limited. This study aimed to investigate the altered gene expression patterns between metastasis and non-metastasis samples using high-throughput RNA and methylation profiles from a large number of patients. Another aim was to identify a specific potential metastasis biomarker, with the ability to predict the metastasis possibility and prognosis of patients with STAD. In this study, we integrated The Cancer Genome Atlas (TCGA) program STAD datasets, analyzed the RNA expression and DNA methylation data between non-metastasis (M0) and distant metastasis (M1) samples, and evaluated the candidate biomarker in survival and prognosis of GC. Among all patients enrolled, 329 with M0 and M1 information were positive for RNA analysis, and 353 with M0 and M1 information were positive for methylation analysis. We found 29 upregulated and 200 downregulated genes in RNA level, and 5,046 hypermethylated and 8,563 hypomethylated probes in methylation level. Among these genes, we found high RNA expression level and low DNA methylation level of ALOX12B and PACSIN1 in GC metastasis samples. Patients with high expression of these 2 genes had poor overall survival (OS), progression-free survival (PFS), and post-progression survival (PPS). The expression levels of ALOX12B and PACSIN1 were higher in the metastasis than non-metastasis group, and participants with high expression of these 2 genes were found to have poor survival. The genes ALOX12B and PACSIN1 are potential biomarkers of metastasis and poor prognosis, especially in early stage GC, and provide additional information for subsequent comprehensive treatment of GC.

P26.01 Detecting Oligo-Metastatic/Progressive Disease in Advanced EGFR-Mutant NSCLC: PET/CT and Conventional Imaging Methods

Local ablative therapy (LAT) could potentially prolong patient's survival in advanced EGFR-mutant non-small cell lung cancer (NSCLC) receiving first-line EGFR tyrosine kinase inhibitors (TKIs) and harboring oligo-metastatic/progressive (OMD/OPD). However, the exact frequency of OMD/OPD and the optimal imaging method for identifying patients with OMD/OPD remain controversial. Consecutive cases with first-line EGFR-TKI treated metastatic EGFR-mutant NSCLC were retrospectively screened and those receiving PET/CT or complete conventional imaging methods (CIM), including brain MRI, chest CT, abdomen ultrasound or CT and bone scintigraphy, at baseline were included. OMD/OPD was defined as metastases/progressions documented at a maximum of 5 lesions (all thoracic lymph nodes as one lesion) and 3 organs, otherwise was referred to as multiple-metastatic/progressive disease (MMD/MPD). OMD was detected in 53 (22.7%) of 233 patients evaluated by PET/CT and 29 (18.2%) of 159 patients evaluated by CIM at baseline. Among the patients evaluated with baseline PET/CT, time to treatment failure (TTF) tended to be longer in patients with OMD than those with MMD (p=0.061) and concurrent LAT significantly prolonged TTF in patients with OMD (28.0 vs 18.1 months, p=0.027). However, this was not the case among the patients evaluated with baseline CIM. With a median follow-up of 24.2 (range, 1.1-117.6) months, initial disease progression (FPD) was documented in 297 patients, 147 (49.5%) of whom had adequate imaging scans to comprehensively analyze the tumor distributions at FPD. OPD was detected in 23 (62.2%) of the 37 patients evaluated by PET/CT at both baseline and FPD (PET/CT group), 16 (39.0%) of the 41 patients evaluated by CIM at both baseline and FPD (CIM group), and 23 (33.0%) of the 69 patients evaluated by PET/CT at baseline and CIM at FPD (PET/CT-CIM group), respectively. The post-progression overall survival (OS2) was significantly longer for patients with OPD than those with MPD (p=0.032) in the PET/CT group, but was similar in the other two groups. Disease progression only at the originally existed sites (original PD) was detected in 43.2%, 26.8% and 65.2% of patients with FPD in the PET/CT, CIM and PET/CT-CIM group, respectively. Patients with only original PD had significantly longer OS2 (p=0.004) in the PET/CT group, but was not the case in the other two groups. PET/CT has better performance in detecting OMD/OPD in first-line EGFR-TKI treated advanced EGFR-mutant NSCLC. Patients with PET/CT-detected OMD may benefit from appropriate LATs.

The Expression Patterns and Prognostic Value of the Proteasome Activator Subunit Gene Family in Gastric Cancer Based on Integrated Analysis.

Increasing evidence supports that proteasome activator subunit (PSME) genes play an indispensable role in multiple tumors. The diverse expression patterns, prognostic value, underlying mechanism, and the role in the immunotherapy of PSME genes in gastric cancer (GC) have yet to be fully elucidated. We systematically demonstrated the functions of these genes in GC using various large databases, unbiased in silico approaches, and experimental validation. We found that the median expression levels of all PSME genes were significantly higher in GC tissues than in normal tissues. Our findings showed that up-regulated PSME1 and PSME2 expression significantly correlated with favorable overall survival, post-progression survival, and first progression survival in GC patients. The expression of PSME1 and PSME2 was positively correlated with the infiltration of most immune cells and the activation of anti-cancer immunity cycle steps. Moreover, GC patients with high PSME1 and PSME2 expression have higher immunophenoscore and tumor mutational burden. In addition, a receiver operating characteristic analysis suggested that PSME3 and PSME4 had high diagnostic performance for distinguishing GC patients from healthy individuals. Moreover, our further analysis indicated that PSME genes exert an essential role in GC, and the present study indicated that PSME1 and PSME2 may be potential prognostic markers for enhancing survival and prognostic accuracy in GC patients and may even act as potential biomarkers for GC patients indicating a response to immunotherapy. PSME3 may serve as an oncogene in tumorigenesis and may be a promising therapeutic target for GC. PSME4 had excellent diagnostic performance and could serve as a good diagnostic indicator for GC.

OTUB2 Facilitates Tumorigenesis of Gastric Cancer Through Promoting KDM1A-Mediated Stem Cell-Like Properties.

Otubain 2 (OTUB2), a deubiquitinating enzyme, overexpression is considered to predict poor outcome in various cancers. However, the function and potential regulatory mechanisms of OTUB2 in gastric cancer (GC) progression remains unclear. To determine how OTUB2 participate in GC progression, the gain and loss of-function experiments were conducted in vivo and in vitro. We found that OTUB2 was upregulated in GC samples (n=140) and cells. Moreover, the overall, first progression and post progression survival rates of GC patients with high OTUB2 expression showed a poorer prognosis than that in those patients with low OTUB2 expression. Down-regulation of OTUB2 suppressed sphere formation and reduced expression of stem cell markers in GC cells. Furthermore, OTUB2-silenced GC cells also showed a decreased proliferation, invasion, migration, and in vivo tumorigenic ability. However, OTUB2 overexpression showed the opposite effects. Notably, we demonstrated that OTUB2 increased lysine-specific histone demethylase 1A (KDM1A) expression through deubiquitination. KDM1A, a demethylase known to promote demethylation of downstream genes, was identified to promote the maintenance of cancer stem cell characteristics. Moreover, the alterations caused by OTUB2 overexpression were partly inversed by KDM1A knockdown and in turn KDM1A overexpression reversed the changes induced by OTUB2 shRNA. Taken together, we demonstrate that OTUB2 may serve as a vital driver in GC tumorigenesis by enhancing KDM1A-mediated stem cell-like properties.

Changes in the Mean Intrahepatic Target Computed Tomography Attenuation Value During Treatment May Be a Useful New Predictor of the Post-progression Survival Associated with Lenvatinib Treatment.

Objective The relationship between the prognosis and magnitude of a decrease in tumor blood flow according to estimated tumor differentiation remains unclear. This study investigated the relationship between reductions in the rate of mean computed tomography (CT) attenuation values and the clinical prognosis. Methods We evaluated 63 consecutive patients who received lenvatinib treatment for unresectable hepatocellular carcinoma (HCC). The oncological aggressiveness of the tumors was estimated using classification by dynamic CT enhancement patterns. The utility of changes in mean CT attenuation values of intra-hepatic targets during treatment to estimate the prognosis was investigated by calculating the progression-free survival (PFS) and post-progression survival (PPS). A multivariate analysis was used to identify potential confounders for the survival after progression during lenvatinib therapy. Results The rate of decrease in the mean CT attenuation value gradually increased according to the degree of deterioration in estimated tumor differentiation, and the rate of a decrease in attenuation ≥40% showed a tendency to increase (p=0.064). This trend was reflected by a better objective response in oncological aggressiveness heterogeneous enhancement patterns (Type-3 and Type-4) than a homogeneous enhancement pattern (Type-2) (83% vs. 56% of modified Response Evaluation Criteria in Solid Tumors). This resulted in a similar PFS between the groups (p=0.773), whereas the PPS was significantly worse when the rate of decrease in the attenuation value was ≥40% (p=0.012). A multivariate analysis confirmed that a rate of decease in attenuation value ≥40% was a poor prognostic factor for the PPS (hazard ratio, 2.993; 95% confidence interval, 1.196-7.490; p=0.019). Conclusion A rate of decrease in attenuation ≥40% may reflect a good response of a highly malignant tumor to lenvatinib. Therefore, this value may have utility as a surrogate marker for estimating the oncological aggressiveness of tumors and their associated prognosis.

Course of postoperative relapse in non-small cell lung cancer is strongly associated with post-progression survival.

BackgroundFor early‐stage non‐small cell lung cancer (NSCLC), surgical resection is considered the most effective treatment strategy and curative treatment. Unfortunately, even after complete resection, almost half of all patients with stage I–IIIA NSCLC relapse and die. Although the possibility of a cure for postoperative recurrence of NSCLC is significantly low, the course of subsequent treatment can possibly affect overall survival (OS). Here, we examined the association of relapse‐free survival (RFS) and post‐progression survival (PPS) with OS in patients with postoperative recurrence of NSCLC.MethodsWe evaluated 128 patients with NSCLC who underwent complete resection between January 2007 and December 2018. The association between RFS and PPS on OS was examined at the patient level.ResultsSpearman's rank correlation and linear regression analyses revealed that PPS was strongly correlated with OS (r = 0.83, p < 0.05, R 2 = 0.72), whereas RFS was weakly associated with OS (r = 0.56, p < 0.05, R 2 = 0.37). Additionally, the performance status at relapse and administration of tyrosine kinase inhibitors were significantly correlated with PPS.ConclusionsPPS was significantly more strongly correlated with OS than was RFS in patients with postoperative recurrence of NSCLC. These results suggest that therapy following postoperative recurrence affects OS. Therefore, it is necessary to validate these promising results in a large prospective study.

Comprehensive Analysis of the Prognostic Value and Immune Function of Immune Checkpoints in Stomach Adenocarcinoma.

BackgroundStomach adenocarcinoma (STAD) is one of the most prevalent malignances and ranks fifth in incidence and third in the cancer-related deaths among all malignances. The prognosis of STAD is poor. Immunotherapy based on immune checkpoint blockade is ever-increasingly suggested as the most promising therapy strategy for STAD. However, the prognosis and therapy value of immune checkpoints in STAD is far from clarified.MethodsIn our study, bioinformatics methods were performed to explore the expression and prognosis value of immune checkpoints in STAD and their association with immune infiltration. qRT-PCR was performed to verify our result.ResultsMost of the immune checkpoints were upregulated in STAD. There were lots of genetic mutations among immune checkpoints in STAD, including missense_mutation, frame_shift_del et al. Interestingly, most of immune checkpoints were associated with drug sensitivity and drug resistance. Moreover, CD274, PVR, LGALS9, ICOSLG and CD70 were associated with the overall survival, post progression survival and first progression in STAD. The univariate and multivariate analysis revealed that CD70, ICOSLG, age, pTNM stage, and radiation therapy were independent factors affecting the prognosis of STAD patients. The expression of ICOSLG and CD70 was correlated with immune cells as well as immune biomarkers, including CD8+ T cells, CD4+ T cells, macrophage, neutrophils and dendritic cells.ConclusionAll in all, our study performed a comprehensive analysis of the prognostic value and immune function of immune checkpoints in STAD, and our result suggested that immune checkpoint ICOSLG and CD70 serve as prognostic biomarkers and associate with immune infiltration in STAD.

Comprehensive Analysis of E2F Family Members in Human Gastric Cancer.

Gastric cancer (GC) is the second most common cancer and the third most frequent cause of cancer-related deaths in China. E2Fs are a family of transcription factors reported to be involved in the tumor progression of various cancer types; however, the roles of individual E2Fs are still not known exactly in tumor progression of GC. In this study, we examined the expression of E2Fs to investigate their roles in tumor progression in GC patients using multiple databases, including ONCOMINE, GEPIA2, Kaplan-Meier plotter, cBioPortal, Metascape, LinkedOmics, GeneMANIA, STRING and UCSC Xena. We also performed real-time polymerase chain reaction (RT-PCR) to validate the expression levels of individual E2Fs in several GC cell lines. Our results demonstrated that the mRNA levels of E2F1/2/3/5/8 were significantly higher both in GC tissues and cell lines. The expression levels of E2F1 and E2F4 were correlated with poor overall survival (OS), decreased post-progression survival (PPS), and decreased progression-free survival (FP) in patients with GC. However, overexpression of E2F2, E2F5, E2F7 and E2F8 is significantly associated with disease-free survival and overall survival in patients with GC. In addition, higher E2F3 and E2F6 mRNA expression was found to increase GC patients’ OS and PPS. 224 of 415 patients with STAD (54%) had gene mutations that were associated with longer disease-free survival (DFS) but not OS. Cell cycle pathway was closely associated with mRNA level of more than half of E2Fs (E2F1/2/3/7/8). There were close and complicated interactions among E2F family members. Finally, our results indicated the gene expressions of E2Fs had a positive relationship with its copy numbers. Taken together, E2F1/2/3/5/8 can serve as biomarkers for GC patients with high prognostic value for OS of GC patients or therapeutic targets for GC.

A systematic literature review of prognostic factors in patients with HR+/HER2- advanced breast cancer in Japan.

BackgroundBreast cancer is the most prevalent cancer in women in Japan and the fifth in mortality. This systematic review summarized the evidence for prognostic factors for patients with HR+/HER2− advanced and metastatic breast cancer in Japan.MethodsMEDLINE and EMBASE were searched with keywords ‘breast neoplasms’ AND ‘Japan’ AND ‘advanced’ or equivalent, and Japan Medical Society database with ‘breast cancer’ AND ‘advanced/metastatic’ for publications from January 2010 to October 2019. ASCO, ESMO, ABC4 abstracts and WHO website were hand searched. The endpoints of interest were overall survival, progression-free survival, tumour response and post-progression survival. Factors were evaluated based on the consistency in direction and the strength (hazard ratios) of association.ResultsSearches identified 4530 publications, of which 27 were eligible. All were observational studies. Among the endpoints, overall survival was the most commonly assessed (n = 22) and evaluated further. Ki-67 expression, progesterone receptor expression status, tumour grade and lymph node metastases were consistently associated with poor overall survival in univariate analysis but not in multivariate analysis. Short disease-free interval, the number of metastatic organs and liver metastasis were consistently associated with poor overall survival in both of univariate and multivariate analysis. The association was strong for liver metastasis (hazard ratio ≥2.8 in the majority of studies) and moderate for disease-free interval and the number of metastatic organs (hazard ratio 1.3–2.8 in the majority of studies).ConclusionsDisease-free interval, the number of metastatic organs and liver metastasis were identified as independent prognostic factors for overall survival. These findings may help clinical decision-making to improve outcomes in patients with HR+/HER2− advanced and metastatic breast cancer.

Real-world evaluation of second line chemotherapy for patients with advanced non-small cell lung cancer harboring preexisting interstitial lung disease.

The optimal second and subsequent lines of chemotherapy for patients with non-small cell lung cancer (NSCLC) who have preexisting interstitial lung disease (ILD) are unclear. Hence, we examined the clinical efficacy and safety of second-line chemotherapy in such patients, including any exacerbation of preexisting ILD. The medical records of patients with NSCLC and preexisting ILD who received both first- and second-line chemotherapy were retrospectively reviewed. Twenty-four patients with a median age of 71years who were treated between April 2013 and March 2021 were included. The response rate after second-line chemotherapy with S-1 (n = 13), docetaxel (n = 8), pemetrexed (n = 2), or docetaxel plus ramucirumab (n = 1) was 12.5%, with a median progression-free survival (2nd line PFS) of 3.8months. The overall survival from a start of first-line chemotherapy (1st line OS) and post-progression survival (PPS) post-first-line chemotherapy were 18.7 and 9.7months, respectively. Spearman rank correlation and linear regression analyses showed that PPS was strongly correlated with 1st line OS (R = 0.85, P < 0.00001). Importantly, the 2nd line PFS was also significantly correlated with 1st line OS (R = 0.71, P = 0.0001). While second-line chemotherapy-related acute exacerbation of ILD was observed in 7 patients (29.2%), there were no treatment-related fatalities. Conslusions. Second-line chemotherapy has a strong positive impact on the OS of patients with NSCLC who have preexisting ILD. Given the findings of this study, second-line chemotherapy may be valuable in terms of prolonging long-term OS.

Expression and clinical significance of AURKB gene in lung adenocarcinoma: Analysis based on the data-mining of bioinformatic database.

This study aimed to investigate the expression and clinical significance of aurora B kinase (AURKB) gene in lung adenocarcinoma (LUAD) by collecting relevant data in Oncomine database.Firstly, mRNA expression level of AURKB in LUAD was systematically analyzed using the ONCOMINE and the cancer genome atlas databases. Then, the association between AURKB expression and clinical parameters was investigated by UALCAN. The Kaplan–Meier Plotter was used to assess the prognostic significance of AURKB.Pooled analysis showed that AURKB was frequently up-regulated expression in LUAD. In addition, immunohistochemistry showed that AURKB was highly expressed in lung adenocarcinoma tissues, while it was weakly expressed in normal tissues. Subsequently, AURKB expression was identified to be negatively associated with Overall survival (P < 1e−16), post-progression survival (P = .017), first progression (P = 9.8e−09).This study confirms that increased expression of AURKB in LUAD is associated with poor prognosis, suggesting that AURKB might be used as a promising prognostic biomarker and novel therapeutic target for LUAD.

NMU Is a Poor Prognostic Biomarker in Patients with Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most prevalent histologic type of lung cancer, associated with a high incidence rate and substantial mortality rate worldwide. Accumulating evidence shows that the aberrant expression of neuromedin U (NMU) contributes to the initiation and progression of cancer. Herein, we explored whether NMU could be adopted as a new diagnostic and therapeutic marker in LUAD. The UALCAN and GEPIA web resources were employed to assess data on the NMU expression in LUAD. The STRING web resource was used to develop the PPI (protein-protein interaction) network of NMU, whereas Cytoscape was applied for module analysis. The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of NMU and the interacting proteins were examined using the WebGestalt tool. Survival analysis was performed with the Kaplan-Meier plotter tool. Results revealed that the NMU expression in LUAD was significantly higher than in the nonmalignant tissues. Moreover, higher NMU levels were dramatically related to shorter overall survival, first progression survival, and postprogression survival. The specific gene mutations G45V, R143T, and F152L of NMU occurred in LUAD samples and were associated with a worse prognosis in patients. KEGG and western blot analyses demonstrated an association of NMU with the cell cycle and the cAMP signaling cascade. Bioinformatic analysis and the in vitro experiments implicated NMU as a promising prognostic signature and treatment target for LUAD.

Post-Progression Survival Influences Overall Survival among Patients with Advanced Non-Small Cell Lung Cancer Undergoing First-Line Pembrolizumab Monotherapy

Background: Among patients with non-small cell lung cancer (NSCLC), the impact of first-line treatment on overall survival (OS) may be influenced by subsequent therapies. Thus, using patient-level data, we assessed the relationships of progression-free survival (PFS) and post-progression survival (PPS) with OS among patients with high-programmed death-ligand 1 (PD-L1) expression undergoing first-line pembrolizumab monotherapy for NSCLC. Methods: We reviewed data from 133 patients with high PD-L1 expression undergoing first-line pembrolizumab monotherapy for NSCLC at 6 Japanese centers between February 2017 and December 2018. The correlations of PFS and PPS with OS were evaluated at the patient level. Results: Linear regression analyses and Spearman’s rank correlation coefficient revealed that PPS was strongly correlated with OS (r = 0.76, p < 0.05, R² = 0.65), while PFS was only moderately correlated with OS (r = 0.71, p < 0.05, and R² = 0.4). Furthermore, PPS was significantly associated with performance status at the end of pembrolizumab monotherapy, as well as the use of platinum-based combination chemotherapy after pembrolizumab monotherapy (both p < 0.05). Conclusions: Among patients with high PD-L1 expression undergoing first-line pembrolizumab monotherapy for NSCLC, PPS was more strongly correlated with OS, relative to the relationship between PFS and OS. Therefore, subsequent treatment appears to significantly influence OS in patients with disease progression following first-line pembrolizumab monotherapy.

The use of bevacizumab is correlated with improved post-progression survival in advanced recurrent ovarian cancer.

The recent improvements in anti-cancer therapy following first-line treatment can potentially impact post-progression survival. We evaluated the factors that influence post-progression survival in advanced recurrent ovarian cancer. Eighty-nine patients who underwent first-line treatment between June 2005 and December 2017 were included. The post-progression survival was defined as the difference between overall survival and initial progression-free survival. The effects of age, histology, stage, optimal surgery, secondary debulking surgery, bevacizumab administration, platinum sensitivity, and olaparib maintenance in recurrence were compared and independent risk factors were determined. The median follow-up duration was 60.0months (range: 2-181). Platinum-sensitive recurrence had longer post-progression survival than platinum-resistant (P<0.001). Inclusion of bevacizumab in first-line treatment did not produce a significant difference in post-progression survival (P=0.462). Secondary debulking surgery (P=0.013), bevacizumab administration (P<0.001), and olaparib maintenance (P=0.001) during recurrence increased post-progression survival. In multivariate analysis, histologies other than serous or endometrioid (hazard ratio=2.389; 95% confidence interval=1.200-4.754; P=0.013) and non-bevacizumab usage in recurrence (hazard ratio=4.484; 95% confidence interval=1.939-10.370; P<0.001) were independently correlated with poorer prognosis. Bevacizumab administration beyond progressive disease elicited improved post-progression survival (P<0.001). In patients receiving bevacizumab in first-line treatment, exclusion of bevacizumab in the recurrent therapy (hazard ratio=5.507; 95% confidence interval=2.301-12.124; P<0.001) was independently correlated with poorer prognosis. The continuous use of bevacizumab beyond progressive disease improves post-progression survival suggesting its important role in first-line and recurrence treatment for ovarian cancer.

CDCA1/2/3/5/7/8 as novel prognostic biomarkers and CDCA4/6 as potential targets for gastric cancer.

BackgroundIncreasing evidence had suggested that cell division cycle-associated (CDCA) family proteins play prominent roles in multiple types of cancer. However, the expression pattern and prognostic value of CDCAs in gastric cancer were still poorly understood.MethodsIn this study, bioinformatics was used for the first time to comprehensively discuss the expression changes of the CDCA protein family in gastric cancer. We studied the transcription and survival data of CDCAs in patients with gastric cancer in Oncomine, GEPIA, DAVID, cBioportal, and other databases.ResultsWe identified that the CDCA 1/2/3/4/5/6/7/8 were overexpressed gastric cancer than in normal tissues. There was no significant difference in CDCAs expression among different gastric cancer stages. High expression of CDCA4/6 in patients with gastric cancer was closely related to low overall survival (OS), first progression survival (FPS), and post-progression survival (PPS). In contrast, high CDCA1/2/3/5/7/8 expression predicted a better prognosis. The genetic mutation rate of CDCA2 and CDCA4 was 4%, ranking first. The main biological process of CDCAs protein family enrichment was cell division, the main cell component involved was centromeres of chromosomes, and the main molecular function involved was protein binding.ConclusionsThe study suggested that CDCA1/2/3/5/7/8 were expected to be new prognostic markers for gastric cancer, and CDCA4/6 might be potential targets for the treatment of gastric cancer.

Bioinformatics Analysis of KIF1A Expression and Gene Regulation Network in Ovarian Carcinoma.

BackgroundThe study aims to analyze the expression levels of kinesin family member 1A (KIF1A) in ovarian cancer (OC) and explore its clinical significance in the development of OC and its potential regulatory network.MethodsThe Cancer Genome Atlas (TCGA) OC data was used to examine the expression differences between OC and normal tissue and explore the correlation with tumor stage. The relationship between KIF1A expression and prognosis was analyzed using Oncomine and Kaplan–Meier plotter tools. The co-expression network of KIF1A in TCGA OC was analyzed based on the application of cBioPortal, GO cluster, and KEGG analyses were performed based on the co-expression network. Immune-infiltration analysis were used to analyze the significant involvement of KIF1A in function.ResultsKIF1A was highly elevated in OC tissues and KIF1A expression was significantly correlated with the FIGO stage (P=0.015) and age (P=0.020). High KIF1A expression of OC predicted the poor prognosis including overall survival (OS) (HR: 1.27; 95% CI: 1.11–1.45; P=0.00046) and post-progression survival (PFS) (HR: 1.18; 95% CI: 1.03–1.35; P=0.015). GO and KEGG analysis showed KIF1A had a potential role in the biological process of ATP-dependent chromatin remodeling, transcription, DNA-templated cytolysis, positive regulation of T cell proliferation, positive regulation of transcription, DNA-templated via cell adhesion molecules (CAMs), primary immunodeficiency, oxidative phosphorylation, NF-kappa B signaling pathway, pathways in cancer and Wnt signaling pathway, and immune infiltrating cells.ConclusionKIF1A was highly expressed and correlated with poor survival and immune infiltration in OC, and it may be a prognostic biomarker in OC.

Early Disease Progression Predicts Poorer Survival in Patients with Follicular Lymphoma (FL) in the GALLIUM Study

Early Disease Progression Predicts Poorer Survival in Patients with Follicular Lymphoma (FL) in the GALLIUM Study

Is Obinutuzumab Plus Chemotherapy Followed By Obinutuzumab Monotherapy for Previously Untreated Follicular Lymphoma Patients Cost-Effective in the US?

BackgroundObinutuzumab (GA101; G) in combination with chemotherapy followed by G maintenance (G+chemo) has demonstrated superior progression-free survival (PFS) relative to the combination of Rituximab and chemotherapy followed by R maintenance (R+chemo) for previously untreated patients with follicular lymphoma (FL) in the phase III GALLIUM clinical trial (NCT01332968) (Hiddemann et al., European Hematology Association, 2017). The net clinical benefit and economic value of G+chemo vs. R+chemo in a previously untreated FL patient population have not been formally evaluated. The objective of this study was to estimate the cost-effectiveness of G+chemo vs. R+chemo based on results of the GALLIUM trial.MethodsIn the GALLIUM trial, patients received chemotherapy (8 x 21-day cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP], 8 x 21-day cycles of cyclophosphamide, vincristine, and prednisone [CVP], or 6 x 28-day cycles of bendamustine) and were randomized to receive either R 375mg/m2 on Day (D) 1 of each cycle or G 1000mg on D1, 8 and 15 of Cycle 1 and D1 of subsequent cycles. Patients with a complete response or partial response at the end of induction as per modified Cheson criteria received R or G every 2 months for 2 years or until disease progression. We developed a Markov model that utilized the GALLIUM trial's independent review committee (IRC) assessed progression-free survival (PFS), and post-progression survival (PPS) to model overall survival (OS). Drug utilization, treatment duration and adverse events were based on trial data. Costs include drugs, adverse events, monitoring and follow-up care upon disease progression; health care costs were based on Medicare reimbursements and drug costs were July 2017 average sale price (ASP) for intravenous therapies or wholesale acquisition cost (WAC) for oral therapies used post-progression. Utility estimates were based on the GALLIUM trial data and published literature to derive the quality of life impact and compute the quality-adjusted life years (QALY). Sensitivity analyses were conducted to assess the key drivers of the model and uncertainty in the results.ResultsTreatment with G+chemo led to an increase in quality-adjusted life years (QALYs) relative to R+chemo of 0.79 (95% Credible Range (CR) 0.19, 1.36) (Table 1). The total cost of G+chemo was $217,000 and R+chemo was $215,100 resulting in an incremental cost of $1,800 (95% CR: -$7,800, $10,000). The average total cost was greater for G+chemo due primarily to increased drug and administration costs ($137,100 for G+chemo vs. $126,300 for R+chemo), however this was largely offset by cost-savings for disease progression of -$10,100 ($75,700 for G+chemo vs. $85,600 for R+chemo). Adverse event costs were higher for G+chemo ($4,200) vs. R+chemo ($3,300). The incremental cost-effectiveness ratio was $2,249 per QALY gained. In probabilistic sensitivity analyses, there was a 98% and 99% probability that G+chemo was cost-effective versus R+chemo at the $50,000 and $100,000 per QALY thresholds, respectively. There was a high probability G+chemo was cost effective even when all parameters in the model were varied.ConclusionsOur US-based analysis suggests that treatment with G+chemo compared to R+chemo is cost-effective in previously untreated patients with FL. The cost-effectiveness of G+chemo is driven by delaying expensive progression treatments and increasing quality adjusted life years. In conclusion, G+chemo vs. R+chemo in previously untreated FL patients is very likely cost effective in the US. [Display omitted] DisclosuresGuzauskas:Genentech, Inc.: Consultancy. Masaquel:Genentech Inc.: Employment, Other: I Receive Roche stock options. Thuresson:F. Hoffmann-La Roche Ltd: Employment. Li:Genentech: Employment, Equity Ownership. Reyes:Genentech Inc.: Employment, Equity Ownership. Veenstra:Genentech, Inc.: Consultancy.