Independent Predictor Of Poor Overall Survival Research Articles

Comparison of age-stratified survival outcomes of gallbladder cancers in an Indian population

BackgroundGallbladder cancers (GBCs) occur a decade earlier in India in comparison to the global occurrence, limiting the applicability of existing literature on age adjusted outcomes. MethodsPatients who underwent surgery between 01.01.2010 and 31.12.2020 for GBC were analyzed. Patients were divided into three age groups: group 1(≤40 years), group 2(41–60 years), group 3(>60 years) and their outcomes were compared. ResultsTotal of 6190 patients were treated for suspected or diagnosed GBC with a median age of 57 years. Curative resection was performed in 749 (67.9%) patients, of whom 114 (16.2%), 471 (62.9%), and 164 (21.9%) patients were in groups 1, 2, and 3, respectively. 5-year disease-free survival (DFS) [46.8% vs. 58.5%, p = 0.031] and overall survival (OS)[53.5% vs. 66.6%, p = 0.05] of group 3 were significantly lower than group 1. Patient age (HR 1.021), AJCC stage (HR 6.413), pathologic residual disease in the gallbladder fossa (HR 2.44), and extranodal tumor deposits (HR 1.762) were identified as independent predictors of poor OS. ConclusionsGallbladder cancers in the Indian population show poorer outcomes with advancing age. Higher proportion of males in the elderly group with a more advanced stage at presentation are plausible reasons for poorer outcomes.

Impacts of tumor microenvironment during neoadjuvant chemotherapy in patients with esophageal squamous cell carcinoma.

With the advent of immune checkpoint inhibitors (ICIs), a better understanding of tumor microenvironment (TME) is becoming crucial in managing esophageal squamous cell carcinoma (ESCC) patients. We investigated the survival impact of TME status and changes in patients with ESCC who underwent neoadjuvant chemotherapy (NAC) followed by surgery (n = 264). We examined immunohistochemical status (CD4+, CD8+, CD20+, Foxp3+, HLA class-1+, CD204+, and programmed death ligand-1 [PD-L1+]) on 264 pre-NAC and 204 paired post-NAC specimens. Patients were classified by their pre- and post-NAC immune cell status and their changes following NAC. Our findings showed that pre-NAC TME status was not significantly associated with survival outcomes. In contrast, post-NAC TME status, such as low level of T cells, CD4+ T cells, and high PD-L1 combined positive score (CPS), were significantly associated with poor overall survival (OS). Notably, TME changes through NAC exerted significant survival impacts; patients with consistently low levels of T cells, low levels of CD4+ T cells, or high levels of PD-L1 (CPS) had very poor OS (3-year OS: 35.5%, 40.2%, and 33.3%, respectively). Tumor microenvironment changes of consistently low T cells, low CD4+ T cells, and high PD-L1 were independent predictors of poor OS in multivariate Cox hazards analyses, while factors indicating post-NAC status (T cells, CD4+, and PD-L1 [CPS]) alone were not. Therefore, we suggest that the consistently low T/high PD-L1 group could benefit from additional therapies, such as ICIs, and the importance of stratification by the TME, which has recently been recognized.

Prognostic factors of palatal adenoid cystic carcinoma: A single-center analysis of 85 cases.

The purpose of this retrospective study was to describe the clinicopathological characteristics of primary adenoid cystic carcinoma (ACC) of the palate and to identify the factors affecting prognosis. The medical records of 85 patients with primary ACC of the palate treated with surgery, with or without adjuvant radiotherapy/chemotherapy, from 2009 to 2019 were reviewed. The relationship of different clinical parameters with locoregional recurrence (LR), distant metastasis (DM), and overall survival (OS) were analyzed. Median follow-up time was 44.6 months. LR and DM rates were 24.7% and 25.9%, respectively, and the 5-year OS and disease-free survival (DFS) rates were 85.9% and 55.1%, respectively. Multivariate analysis showed that positive margins were independently associated with the risk of LR (p < .001). Positive margins (p = .001) and high histological grade (p = .031) were significantly associated with shorter OS. Positive surgical margins are a strong adverse prognostic factor affecting LR and OS in patients with ACC; apart from that, high histopathological grade is an independent predictor of poor OS. Level 3 (Prognosis - Cohort study).

Predictive nomograms of repeat intrahepatic recurrence and overall survival after radiofrequency ablation of recurrent colorectal liver metastases

Objectives This study was conducted to develop nomograms for predicting repeat intrahepatic recurrence (rIHR) and overall survival (OS), after radiofrequency ablation (RFA), treatment in patients with recurrent colorectal liver metastases (CLMs) after hepatectomy based on clinicopathologic features. Methods A total of 160 consecutive patients with recurrent CLMs after hepatectomy who were treated with ultrasound-guided percutaneous RFA from 2012 to 2022 were retrospectively included. Patients were randomly divided into a training cohort and a validation cohort, with a ratio of 8:2. Potential prognostic factors associated with rIHR and OS, after RFA, were identified by using the competing-risks and Cox proportional hazard models, respectively, and were used to construct the nomogram. The nomogram was evaluated by Harrell’s C-index and a calibration curve. Results The 1-, 2-, and 3-year rIHR rates after RFA were 58.8%, 70.2%, and 74.2%, respectively. The 1-, 3- and 5-year OS rates were 96.3%, 60.4%, and 38.5%, respectively. In the multivariate analysis, mutant RAS, interval from hepatectomy to intrahepatic recurrence ≤ 12 months, CEA level >5 ng/ml, and ablation margin <5 mm were the independent predictive factors for rIHR. Mutant RAS, largest CLM at hepatectomy >3 cm, CEA level >5 ng/ml, and extrahepatic disease were independent predictors of poor OS. Two nomograms for rIHR and OS were constructed using the respective significant variables. In both cohorts, the nomogram demonstrated good discrimination and calibration. Conclusions The established nomograms can predict individual risk of rIHR and OS after RFA for recurrent CLMs and contribute to improving individualized management.

Clinical Significance of Tryptophanyl-tRNA Synthetase 1 Gene Expression in Patients With Locally Advanced Gastric Cancer.

The tryptophanyl-tRNA synthetase 1 gene (WARS1), encodes a tryptophan-tRNA synthetase involved in the amino acidification of tryptophan-tRNA and has been reported to be involved in cancer cell growth, metastasis promotion, and drug resistance in a variety of cancers. This study investigated the clinical significance of WARS1 expression as a biomarker in gastric cancer tissues obtained from patients with locally advanced gastric cancer (GC) who underwent radical resection. WARS1 expression in GC tissues and adjacent normal gastric mucosa of 253 patients with pStage II/III GC who underwent curative resection was determined using quantitative polymerase chain reaction (PCR). Association of WARS1 expression levels, categorized into high and low expression based on the median expression levels, with clinicopathological factors and overall survival (OS) of these patients was assessed. The low-WARS1 expression group had significantly higher serosal invasion, lymph node metastasis, lymphatic invasion, venous invasion, and pathological stage than did the high-WARS1 expression group. OS was significantly worse in the low- than in the high-WARS1 expression group (5-year survival 52.2% vs. 75.9%; p=0.0001). Furthermore, in multivariate analysis, low WARS1 expression was an independent predictor for poor OS (hazard ratio=2.101; 95% confidence interval=1.328-3.322; p=0.002). In patients with locally advanced GC, after curative resection, WARS1 expression in GC tissue may be a useful prognostic marker.

Long-term outcomes and early recurrence after resection for metachronous pulmonary metastases from colorectal cancer.

Properly selecting patients for aggressive curative resection for pulmonary metastases (PMs) from colorectal cancer (CRC) is desirable. We purposed to clarify prognostic factors and risk factors for early recurrence after metachronous PM resection. Clinical data of 151 patients who underwent R0 resection for metachronous PMs from CRC at two institutions between 2008 and 2021 were reviewed. Seventy-six patients (50.3%) were male, and the median age was 71 (42-91) years. The numbers of colon/rectal cancers were 76/75, with pStage I/II/III/IV/unknown in 15/34/86/13/3. The duration from primary surgery to PM was 19.7 (1.0-106.4) months. The follow-up period was 41.9 (0.3-156.2) months. The 1-, 3-, and 5-year recurrence-free survival (RFS) rates were 75.1%, 53.7%, and 51.1%, and the 1-, 3-, and 5-year overall survival (OS) rates were 97.7%, 87.5%, and 68.2%. On multivariate analysis, lymph node metastasis of the primary lesion (HR 1.683, 95%CI 1.003-2.824, p = 0.049) was an independent predictor of poor RFS, and history of resection for extrapulmonary metastasis (e-PM) (HR 2.328, 95%CI 1.139-4.761, p = 0.021) was an independent predictor of poor OS. Patients who experienced early recurrence (< 6months) after PM resection showed poorer OS than others (3-year OS 50.8% vs. 90.2%, p = 0.002). On multivariate analysis, e-PM was an independent predictor of early recurrence after PM resection (OR 3.989, 95%CI 1.002-15.885, p = 0.049). Since a history of e-PM was a predictor of early recurrence and poor OS after R0 resection for PM, surgical treatment of patients with a history of e-PM should be considered carefully.

Identification of potential prognostic biomarkers among gene models for coiled-coil domain-containing family members in hepatocellular carcinoma elucidates their influence on the hypoxia pathway and immune microenvironment.

The family of coiled-coil domain-containing (CCDC) proteins participates in a wide range of physiological functions and plays a pivotal role in governing the invasion and metastasis of malignant tumor cells. Nonetheless, the precise mechanism governing the interaction among the immune microenvironment, hypoxia pathway, and proliferation in hepatocellular carcinoma (HCC) remains elusive. In this study, our objective was to identify the prognostic significance of CCDC family genes in HCC. We conducted an analysis of RNA-seq data from HCC patients sourced from The Cancer Genome Atlas (TCGA) database. Our analysis involved comparing the expression profiles of 168 CCDC family genes between tumor and normal tissues to identify differentially expressed genes (DEGs). The prognostic value of these genes was verified using overall survival (OS) data from TCGA-LIHC patients, employing Univariate and multivariate Cox proportional hazards regression models and Kaplan-Meier plots. Subsequently, we constructed a prognostic signature known as the CCDC score and validated it using additional datasets (ICGC-LIRI-JP and GSE14520). Additionally, we performed functional enrichment analysis and conducted an assessment of the tumor immune microenvironment (TIME). We identified 34 DEGs of the CCDC family. Among them, six DEGs (CCDC6/22/51/59/132/134) were upregulated and associated with poor prognosis. Higher CCDC score was an independent predictor of poor OS in TCGA-HCC patients (P<0.001, HR =2.37), which was validated in the ICGC-LIRI-JP (P=0.021, HR =2.15) and GSE14520 (P=0.002, HR =2.23) datasets. Functional enrichment analysis showed that hypoxia pathway genes were enriched in the high CCDC score group. Furthermore, immune microenvironment analysis demonstrated that high CCDC score was associated with a suppressed TIME caused by the extrinsic immune escape. The CCDC score, derived from six CCDC genes, exhibits remarkable expression levels in liver cancer and holds promise as an independent prognostic indicator. Our bioinformatics analysis revealed a high CCDC score is strongly associated with activation of the hypoxia pathway and an immunosuppressive tumor microenvironment in HCC. This profound finding may serve as a cornerstone for innovative targeted drug therapies and pave the way for further investigations into the underlying mechanisms of CCDC-related carcinogenesis in liver cancer.

Prognostic Value of Holter Monitoring in Light Chain Amyloidosis

(1) Background: To evaluate the predictive value of Holter monitoring for overall survival (OS) of patients with light chain amyloidosis (AL amyloidosis). (2) Methods: 137 patients with newly diagnosed AL amyloidosis who underwent Holter monitoring within 6 months of diagnosis were included. The primary outcome was OS. Landmark analysis was conducted at one-year follow-up. Independent predictors were determined using the log-rank test and multivariate Cox regression analysis. (3) Results: 131 (95.6%) patients received non-transplant therapy, and 32 (23.4%) underwent daratumumab-based chemotherapy. After a median follow-up of 20.3 months, 47 deaths occurred. Atrial tachycardia (AT), conduction delay, and non-sustained ventricular tachycardia (NSVT) were associated with poor OS one year beyond diagnosis in univariate analyses (patients with vs. without AT: 57.3% [95% confidence interval (CI): 47.2–67.4] vs. 81.0% (95% CI: 74.8–87.2), p = 0.039; patients with vs. without NSVT: 33.3% (95% CI: 8.5–58.1) vs. 75.3% (95% CI: 69.8–80.8), p = 0.024; patients with vs. without conduction delay: 41.7% (95% CI: 24.4–59.0) vs. 75.4% (95% CI: 69.7–81.1), p = 0.003]. AT [hazard ratio (HR): 2.6; 95% CI: 1.0–6.5; p = 0.049) and conduction delay (HR: 4.3; 95% CI: 1.3–14.3; p = 0.016) were independent predictors of OS after accounting for age and 2012 Mayo stage. (4) Conclusion: AT and conduction delay in Holter monitoring are independent predictors of poor OS one year beyond diagnosis in AL amyloidosis.

Influence of preoperative body mass index on prognosis for patients with upper urinary tract urothelial carcinoma treated with radical nephroureterectomy.

The impact of body mass index (BMI) on patients with upper urinary tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU) is controversial. Increasing evidence suggests an age-dependent relationship between obesity and outcomes for some solid organ tumors. Herein, we aimed to assess the prognostic value of preoperative BMI in UTUC patients treated with RNU in Taiwan. This was a retrospective single-center study of 468 UTUC patients undergoing RNU during January 2010-December 2017, with preoperative BMI classification and subgroup analysis based on ages of < or ≥ 70years. All UTUC patients underwent RNU and bladder cuff excision. Overall survival (OS), cancer-specific survival, and disease-free survival (DFS) were analyzed. Fisher's exact test, Mann-Whitney U test, Kaplan-Meier method, and Cox regression model were used for data analysis. The median follow-up duration was 36months. Patients with higher versus lower BMI (cutoff: 25kg/m2) showed no differences in OS; older patients had poor OS (hazard ratio [HR] 1.74; 95% confidence interval [CI] 1.24-2.40; p < 0.001). Older age was an independent predictor of poor OS in multivariate Cox regression analysis (p = 0.001). Younger patients with higher BMI (p = 0.02) had better DFS than older patients with no BMI-related survival differences. Higher BMI was an independent predictor of favorable DFS in younger patients in multivariate Cox regression analysis (HR, 0.53; 95% CI 0.28-0.99; p = 0.043). Younger UTUC patients with higher BMI were independently associated with a favorable DFS.

2 years is a reasonable age cut-off level for prognostic assessment of children with hepatoblastoma.

We aimed to elucidate the prognostic significance of age in hepatoblastoma patients. Data from 783 patients with hepatoblastoma were obtained from the Surveillance, Epidemiology and End Results database (2000-2018). The best age cut-off level was determined by X-tile, and the Kaplan-Meier method was used to estimate overall survival (OS) and cancer-specific survival (CSS). The results of the X-tile were verified by selecting the appropriate cut-off value to maximize the difference in survival outcomes at intervals of 1 year. The Cox regression model was used to determine the prognostic impact of risk factors and age. X-tile analysis determined that 2 years was the best cut-off age for OS and CSS. The overall prognosis in the ≥ 2 years group was worse than that in the < 2 years group (OS: p = 0.00017; CSS: p < 0.0001). In Cox univariate analysis, when 2 years was used as the standard group, the numbers of patients in the two groups were similar, with high hazard ratio (HR) value and narrow 95% confidence interval (CI) (OS: HR, 1.834; 95% CI, 1.329 - 2.532; p < 0.001; CSS: HR, 1.988; 95% CI, 1.410 - 2.801; p < 0.001), which was consistent with the age cut-off point determined by X-tile. Cox multivariate analysis showed that age ≥ 2 years, black ethnicity, no surgery, no chemotherapy, distant metastasis, and tumor size ≥ 5 cm were independent predictors of poor OS and CSS. On subgroup analysis, patients aged ≥ 2 years had worse survival if they were Caucasian, had elevated alpha-fetoprotein, tumor size ≥ 5 cm, or distant metastasis. Age is an important prognostic factor for hepatoblastoma. Age ≥ 2 years at diagnosis may predict poor prognosis and more active treatment measures can be implemented.

A Retrospective Exploratory Analysis for Serum Extracellular Vesicles Reveals APRIL (TNFSF13), CXCL13, and VEGF-A as Prognostic Biomarkers for Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.

Neoadjuvant chemotherapy (NAC) is widely used as a standard treatment for early-stage triple-negative breast cancer (TNBC). While patients who achieve pathologic complete response (pCR) have a highly favorable outcome, patients who do not achieve pCR have variable prognoses. It is important to identify patients who are most likely to have poor survival outcomes to identify candidates for more aggressive therapeutic approaches after NAC. Many studies have demonstrated that cytokines and growth factors packaged into extracellular vesicles (EVs) have an essential role in tumor progression and drug resistance. In this study, we examined the role of serum-derived EV-associated cytokines as prognostic biomarkers for long-term outcomes in patients who underwent anthracycline-taxane-based NAC. We isolated extracellular vesicles from the serum of 190 TNBC patients who underwent NAC between 2015 and 2018 at Samsung Medical Center. EV-associated cytokine concentrations were measured with ProcartaPlex Immune Monitoring 65-plex panels. The prognostic value of EV-associated cytokines was studied. We found that patients with high EV_APRIL, EV_CXCL13, and EV_VEGF-A levels had shorter overall survival (OS). We further evaluated the role of these selected biomarkers as prognostic factors in patients with residual disease (RD) after NAC. Even in patients with RD, high levels of EV_APRIL, EV_CXCL13, and EV_VEGF-A were correlated with poor OS. In all subgroup analyses, EV_CXCL13 overexpression was significantly associated with poor overall survival. Moreover, multivariate analysis indicated that a high level of EV_CXCL13 was an independent predictor of poor OS. Correlation analysis between biomarker levels in EVs and serum showed that EV_VEGF-A positively correlated with soluble VEGF-A but not CXCL13. An elevated level of soluble VEGF-A was also associated with poor OS. These findings suggest that EV_APRIL, EV_CXCL13, and EV_VEGF-A may be useful in identifying TNBC patients at risk of poor survival outcomes after NAC.

Surgical Treatment Outcomes of Patients with Non-Small Cell Lung Cancer and Lymph Node Metastases

This study aimed to investigate the appropriate subgroups for surgery and adjuvant chemotherapy in patients with non-small-cell lung cancer (NSCLC) and nodal metastases. We retrospectively reviewed 210 patients with NSCLC and nodal metastases who underwent surgery and examined the risk factors for poor overall survival (OS) and recurrence-free probability (RFP) using multivariate Cox proportional hazards analysis. Pathological N1 and N2 were observed in 114 (52.4%) and 96 (47.6%) patients, respectively. A single positive node was identified in 102 patients (48.6%), and multiple nodes were identified in 108 (51.4%). Multivariate analysis revealed that vital capacity &lt; 80% (hazard ratio [HR]: 2.678, 95% confidence interval [CI]: 1.483–4.837), radiological usual interstitial pneumonia pattern (HR: 2.321, 95% CI: 1.506–3.576), tumor size &gt; 4.0 cm (HR: 1.534, 95% CI: 1.035–2.133), and multiple-node metastases (HR: 2.283, 95% CI: 1.517–3.955) were significant independent risk factors for poor OS. Tumor size &gt; 4.0 cm (HR: 1.780, 95% CI: 1.237–2.562), lymphatic permeation (HR: 1.525, 95% CI: 1.053–2.207), and multiple lymph node metastases (HR: 2.858, 95% CI: 1.933–4.226) were significant independent risk factors for recurrence. In patients with squamous cell carcinoma (n = 93), there were no significant differences in OS or RFP between those who received platinum-based adjuvant chemotherapy (n = 25) and those who did not (n = 68), at p = 0.690 and p = 0.292, respectively. Multiple-node metastases were independent predictors of poor OS and recurrence. Patients with NSCLC and single-node metastases should be considered for surgery despite N2 disease. Additional treatment with platinum-based adjuvant chemotherapy may be expected, especially in patients with squamous cell carcinoma.

Prediction of survival of preoperative colorectal patients: A new tool to assess the interaction of nutritional status and inflammation

Colorectal cancer (CRC) is responsible for the second leading cause of cancer death worldwide. Thus, the aim of this study was to investigate the application of a new nutritional status and inflammatory tool to predict overall survival (OS) in patients with CRC in the preoperative period. Retrospective cohort study with CRC patients of both sexes treated at a hospital unit, aged ≥20 years. Data were extracted between 2007 and 2015. Multivariate Cox's models were employed to predict OS utilizing a new grade classification system (body mass index vs. percentage weight loss - BMI/%WL), inflammatory markers and clinical data. We evaluated 361 patients. BMI/%WL grade 3-4 (HR: 2.01; p=0.001; 95% CI: 1.34-3.02) were independent predictors of poor OS. Moreover, BMI/%WL grade 3-4+neutrophil-to-lymphocyte ratio (NLR) ≥2.4 (HR: 2.79; p=0.001; 95% CI: 1.54-5.03) increased the death risk in 5-years. However, low NLR (<2.4) altered the OS prognostic ability of the BMI/%WL (HR: 1.72; p=0.099; 95% CI: 0.90-3.28). BMI/%WL was independent predictors of poor OS and the interaction with NLR produced an adjustment effect. These associated tools may be useful in the clinical management of preoperative patients with CRC.

Inflammation-related indicators have a potential to increase overall quality of the prostate cancer management: a narrative review.

Increasing evidence suggests that inflammation plays an essential role in cancer development and progression. The levels of inflammation-related indicators are correlated with prognosis across a wide variety of tumor types, including prostate cancer (PCa), but its diagnostic and prognostic value in PCa remains controversial. In the present review, the diagnostic and prognostic value of inflammation-related indicators in PCa patients is investigated. A literature review was performed using the PubMed database, screening articles from English and Chinese journals published mainly from 2015 to 2022. Inflammation-related indicators based on haematological tests have some diagnostic and prognostic value not only when used alone but also in combination with common clinical indicators such as prostate-specific antigen (PSA), and can significantly improve the accuracy of diagnostic results. Elevated neutrophil-to-lymphocyte-count ratio (NLR) is strongly associated with the detection of PCa in men with PSA levels of 4-10 ng/mL. Preoperative NLR levels in localized PCa patients affect their overall survival (OS), cancer-specific survival (CSS), and biochemical recurrence-free survival (BCRFS) after radical prostatectomy (RP). In patients with castration-resistant prostate cancer (CRPC), a high NLR is associated with poorer OS, progression-free survival (PFS), CSS, and radiographic PFS. Platelet-to-lymphocyte-count ratio (PLR) appears to have the greatest accuracy in predicting an initial diagnosis of clinically significant PCa. The PLR also has the potential to predict the Gleason score. Patients with higher PLR levels have a higher risk of death compared to those with a lower PLR. Elevated procalcitonin (PCT) is correlated with the development of PCa and may be useful in improving the diagnostic accuracy of PCa. Elevated C-reactive protein (CRP) levels are an independent predictor of poorer OS in metastatic PCa. Numerous studies have been conducted on the value of inflammation-related indicators in guiding the diagnosis and treatment of PCa. The value of inflammation-related indicators in predicting the diagnosis and prognosis of PCa patients is now becoming clear.

An MRI-Based Prognostic Stratification System for Medical Decision-Making of Multinodular Hepatocellular Carcinoma Patients Beyond the Milan Criteria.

The suitability of hepatectomy among patients with multinodular hepatocellular carcinoma (MHCC) beyond the Milan criteria remains controversial. There is a need for a reliable risk stratification tool among these patients for the selection of ideal candidates of curative resection. To determine the clinicoradiological prognostic factors for patients with MHCC beyond the Milan criteria to further develop a stratification system. Retrospective. 176 patients with pathologically confirmed MHCC beyond the Milan criteria. The 1.5 T scanner, including T1-, T2-, diffusion-weighted imaging, in/out-phase imaging, and dynamic contrast-enhanced imaging. Conventional MRI features and preoperative laboratory data including aspartate aminotransferase (AST) and α-fetoprotein (AFP) were collected and analyzed. Two nomograms incorporating clinicoradiological variables were independently constructed to predict recurrence-free survival (RFS) and overall survival (OS) with Cox regression analyses and verified with 5-fold cross validation. Based on the nomograms, two prognostic stratification systems for RFS and OS were further developed. The Cohen's kappa/intraclass correlation coefficient, C-index, calibration curve, Kaplan-Meier curve, log-rank test. A P value <0.05 was considered statistically significant. AST > 40 U/L, increased tumor burden score, radiological liver cirrhosis and nonsmooth tumor margin were independent predictors for poor RFS, while AST > 40 U/L, AFP > 400 ng/mL and radiological liver cirrhosis were independent predictors for poor OS. The two nomograms demonstrated good discrimination performance with C-index of 0.653 (95% confidence interval [CI], 0.602-0.794) and 0.685 (95% CI, 0.623-0.747) for RFS and OS, respectively. The 5-fold cross validation further validated the discrimination capability of the nomograms. Based on the nomogram models, MHCC patients beyond the Milan criteria were stratified into low-/medium-/high-risk groups with significantly different RFS and OS. The proposed MRI-based prognostic stratification system facilitates the refinement and further subclassification of patients with MHCC beyond the Milan criteria. 4. 2.

Prognostic value of sarcopenia in patients with lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors or immune checkpoint inhibitors.

It remains controversial whether sarcopenia has any significant impact on the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) or immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC). Therefore, in this study, we aimed to assess the association between sarcopenia and clinical outcomes in patients with advanced NSCLC receiving EGFR-TKIs or ICIs as a first-line therapy. We retrospectively enrolled 131 patients with advanced NSCLC treated with first-line EGFR-TKIs or ICIs between 1 March 2019 and 31 March 2021. To estimate sarcopenia, we calculated skeletal muscle index (SMI) as the ratio of skeletal muscle area (cm2) to height squared (m2). Associations between sarcopenia and overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method and log-rank tests, respectively. A Cox proportional hazards regression model was used to assess the factors associated with OS and PFS. The Student's t-test or Mann-Whitney U test was used to compare the SMI between patients with or without objective response and disease control. The chi-squared test was used to compare adverse events (AEs) between patients with and without sarcopenia. Among the 131 patients, 35 (26.7%) were diagnosed with sarcopenia. Sarcopenia was an independent predictor of poor OS and PFS (p < 0.05) overall and in the EGFR-TKI- and ICI-treated cohorts. Among all patients, those with sarcopenia showed significantly shorter OS and PFS than those without sarcopenia (median OS and PFS: 13.0 vs. 26.0 months and 6.4 vs. 15.1 months; both p < 0.001). These associations were consistent across the subtypes of most clinical characteristics. Statistically significant differences between the objective response (OR) and non-OR groups were also observed in the mean SMI (OR group, 43.89 ± 7.55 vs. non-OR group, 38.84 ± 7.11 cm2/m2; p < 0.001). In addition, we observed similar results with disease control (DC) and non-DC groups (DC group, 42.46 ± 7.64 vs. non-DCR group, 33.74 ± 4.31 cm2/m2; p < 0.001). The AEs did not differ significantly between the sarcopenia and non-sarcopenia groups. Sarcopenia before treatment might be a significant predictor of poor clinical outcomes (shorter OS and PFS, fewer ORs, less DC) in patients with advanced NSCLC treated with EGFR-TKIs or ICIs as the first-line therapy.

Prognostic factors for long-term outcome in bifocal hepatocellular carcinoma after resection.

This study aimed to evaluate whether the radiological similarity and clinicopathological factors determine the prognosis in bifocal hepatocellular carcinoma (bHCC) stratified by the Milan criteria. Consecutive patients with pathologically confirmed bHCC examined between January 2016 and December 2018 were retrospectively enrolled and grouped based on the Milan criteria. Two radiologists independently evaluated whether the imaging features of both tumors were consistent or not, which was defined as the radiological similarity. The clinicopathological data were also collected. The multivariable Cox regression was applied to separately identify the independent factors for recurrence-free survival (RFS) and overall survival (OS) in bHCC within and beyond the Milan criteria. A total of 193 patients were evaluated and divided into the within the Milan criteria group (n = 72) and the beyond the Milan criteria group (n = 121). bHCC within the Milan criteria showed a significantly better prognosis than those beyond the criteria. In the within the Milan criteria group, HBV-DNA load >104IU/mL, microvascular invasion (MVI), and different enhancement patterns were independently associated with poor RFS. MVI was an independent prognostic factor for poor OS. In the beyond the Milan criteria group, HBV infection, MVI, increased ratio of the larger to the smaller tumor diameter (RLSD) value, and low comprehensive similarity were associated with shorter RFS, whereas MVI and increased RLSD value were independent predictors for poor OS. Our study revealed that in addition to MVI- and HBV-related factors, similarity in imaging features between lesions of bHCC is associated with the long-term prognosis. • The prognosis of bifocal HCC patients within the Milan criteria is significantly better than those beyond the criteria. • The similarity in imaging features between lesions of bHCC was an independent prognostic factor. • The more similar the bifocal lesions are in imaging features, the better the prognosis is.

HRCT1, negatively regulated by miR-124-3p, promotes tumor metastasis and the growth of gastric cancer by activating the ERBB2-MAPK pathway.

Gastric cancer is the fourth leading cause of cancer-related deaths worldwide. And patient outcomes are poor due to tumor relapse and metastasis. To develop new therapeutic strategies, it is of great importance to explore the mechanism underlying the progression of gastric cancer. Primary gastric cancer samples with lymph node metastases (LNM) and without LNM were subjected to mRNA microarray assay. The differentially expressed genes were confirmed by RT-qPCR. HRCT1 protein expression was further detected using an immunohistochemistry (IHC) assay. In vitro and in vivo assays were performed to investigate the role of HRCT1 in tumor invasion, metastasis, and proliferation. The expressions of the downstream target genes of HRCT1 were detected by microarray, RT-qPCR and Western blot assays. Dual-luciferase reporter and Western blot assays were carried out to identify miRNAs target to HRCT1. HRCT1 was upregulated in gastric cancer, and high expression of HRCT1 was associated with poor overall survival (OS) and disease-free survival (DFS). Moreover, HRCT1protein expression was an independent predictor for poor OS and DFS. HRCT1 could promote gastric cancer cells' migration, invasion, and proliferation in vitro as well as tumor metastasis and growth in vivo. Notably, our data showed that HRCT1 promoted gastric cancer progression by activating the ERBB2-MAPK signaling pathway. At least partially, the expression of HRCT1 could be negatively regulated by miR-124-3p. The upregulated expression of HRCT1 predicts poor survival for patients with gastric cancer. HRCT1 promotes tumor progression by activating the ERBB2-MAPK pathway. HRCT1, negatively regulated by miR-124-3p, may be a potential therapeutic target for patients with gastric cancer.

Low expression of H3K27me3 is associated with poor prognosis in conventional chordoma.

Chordoma is a rare and locally invasive neoplasm, and the prognostic factors are limited. Deregulation of Histone 3 lysine 27 (H3K27) trimethylation (H3K27me3) is considered to be related with poor prognosis in some tumors. The purpose of this study was to detect the expression of H3K27me3 in chordomas and analyze the correlation with clinicopathological features and explore the roles as potential prognostic markers and therapeutic targets. Specimens of 162 chordoma patients (consisting of 156 conventional chordoma, 4 dedifferentiated chordoma and 2 poorly differentiated chordoma) were enrolled in a tissue microarray (TMA) in order to assess the immunohistochemical staining by H3K27me3 antibodies. Correlations between H3K27me3 expression and clinicopathological features were analyzed. Clinical data of the patients were correlated and survival analysis was performed. Kaplan-Meier survival curves and log-rank test were used to analyze the recurrence-free survival (RFS) and overall survival (OS). Multivariate Cox regression analyses were used to identify potential prognostic factors. The expression of H3K27me3 was lower in 37 chordoma patients (37/162, 22.8%), and higher in 125 patients (125/162, 77.2%). H3K27me3-low expression significantly correlated with spine location (P < 0.001), conventional histological subtype (P < 0.001), and recurrence (P < 0.001). Log-rank test showed that H3K27me3-low expression was associated with poor RFS (P =0.027) and OS (P =0.009) in conventional chordoma patients. Cox multivariate analysis revealed that low expression of H3K27me3 was an independent predictor of poor OS (P =0.007) and RFS (P =0.025) in conventional chordoma patients. Our study indicates that low expression of H3K27me3 might be considered as a predictor for poor prognosis and recurrence, and it may provide a potential therapeutic target for conventional chordoma patients.

The Prognostic Role of VEGFR-2 Gene Amplification in Relation to Serum AFP Levels Among Liver-Transplanted Patients with Hepatocellular Carcinoma

Background Hepatocellular carcinoma (HCC) is the most common primary liver neoplasia. Vascular endothelial factor receptor 2 (VEGFR-2) plays an important role in angiogenesis and it has been associated with poor survival in certain other tumor types. Although a recent study also suggested an association between VEGFR-2 expression and HCC, the relationship between VEGFR-2 amplification and HCC is still obscure. Aim To evaluate prognostic role of vascular endothelial growth factor receptor 2 (VEGFR-2) amplification in relation to serum alpha-fetoprotein (AFP) levels and tumor clinicopathological parameters among liver-transplanted patients with HCC. Study design Cohort study Methods A total of 54 formalin-fixed paraffin-embedded and frozen HCC samples from patients who underwent liver transplantation between 2009 and 2015 were analyzed. VEGFR-2 amplification was determined via fluorescence in situ hybridization (FISH) method in tissue samples obtained during liver transplantation and analyzed with respect to serum AFP levels, tumor clinicopathological parameters, and oncological outcomes including recurrence free survival (RFS) and overall survival (OS). Results Amplified VEGFR-2 gene was prominent in 27 (50.0%) patients, while AFP levels were ≥100 ng/mL in 14 (25.9%) patients. Presence of amplified VEGFR-2 gene was associated with significantly shorter RFS time (mean 72.8 vs 101.3 months for positive and negative patients respectively, P = .015), whereas had no significant impact on OS time (median 79.2 vs 93.1 months, respectively, P = .206). Presence versus absence of amplified VEGFR-2 gene was associated with significantly higher levels of AFP (mean±SD 266.6±405.8 vs 40.6±94.6 ng/mL, P = .016) and higher recurrence rate (81.8 vs 18.2%, P = .018), and significantly predicted the AFP levels ≥100 ng/ml (OR, 10.2, 95%CI 1.8-56.9, P = .008). Lymphatic invasion and vascular invasion emerged as independent predictors of poor OS (HR, 12.4 [95% CI, 2.7-57.3], P = .01) and RFS (HR, 8.3 [95% CI, 2.3-29.8], P = .01). Conclusion In conclusion, our findings revealed the presence of amplified VEGFR-2 gene and its association with serum AFP elevation for the first time in HCC. VEGFR-2 amplification was associated with significantly shorter RFS and it emerged as a significant predictor of elevated AFP. Accordingly, our findings seem to indicate the role of AFP elevation in VEGFR-2-mediated tumorigenesis as well as the likelihood of amplified VEGFR-2 gene and high AFP levels to determine the risk status and efficacy of VEGFR-2-inhibitors in HCC liver transplanted patients.