Risk Factors For Survival Outcome Research Articles

The role of autophagy dysregulation in low and high-grade nonmuscle invasive bladder cancer: A survival analysis and clinicopathological association

IntroductionBladder cancer disproportionately affects men and often presents as nonmuscle-invasive bladder cancer (NMIBC). Despite initial treatments, the recurrence and progression of NMIBC are linked to autophagy. This study investigates the expression of autophagy genes (mTOR, ULK1, Beclin1, and LC3) in low and high-grade NMIBC, providing insights into potential prognostic markers and therapeutic targets. Material and methodsA total of 115 tissue samples (n = 85 NMIBC (pTa, pT1, and CIS) and n = 30 control from BPH patients) were collected. The expression level of autophagy genes (mTOR, ULK1, Beclin1, and LC3) and their proteins were assessed in low and high-grade NMIBC, along with control tissue samples using quantitative real-time polymerase chain reaction and western blotting. Association with clinicopathological characteristics and autophagy gene expression was analyzed by multivariate and univariate survival analysis using SPSS. ResultIn high-grade NMIBC, ULK1, P = 0.0150, Beclin1, P = 0.0041, and LC3, P = 0.0014, were substantially downregulated, whereas mTOR, P = 0.0006, was significantly upregulated. The KM plots show significant survival outcomes with autophagy genes. The clinicopathological characters, high grade (P = 0.019), tumor stage (CIS P = 0.039, pT1 P = 0.018, P = 0.045), male (P = 0.010), lymphovascular invasion (P = 0.028) and autophagy genes (ULK1 P = 0.002, beclin1 (P = 0.010, P = 0.022) were associated as risk factors for survival outcome in NMIBC patients. ConclusionThe upregulated mTOR, downregulated ULK1, and beclin1 expression is linked to a high-grade, CIS and pT1 stage, resulting in poor recurrence-free survival and progression-free survival and highlights the prognostic significance of autophagy gene in nonmuscle-invasive bladder cancer.

Associations between R.E.N.A.L. nephrometry score and survival outcomes in renal tumours.

The radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score could be used to predict surgical outcomes and renal tumour aggressiveness. We aimed to analyse its associations with survival outcomes. We included 1368 patients with sporadic, unilateral and non-metastatic renal tumours who received curative nephrectomy in Zhongshan Hospital from January 2009 to September 2019. Radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores were assigned by three urologists based on preoperative CT/MRI scans. Correlations between parameters or sum of radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores, overall survival and recurrence-free survival were analysed by Kaplan-Meier analyses and the multivariate Cox regression model. We further compared survival outcomes between patients who received partial nephrectomy and patients who received radical nephrectomy. We observed statistically significant associations between all components of radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores and oncologic outcomes, including R (radius) (overall survival, P <0.001; recurrence-free survival , P <0.001), E (exophytic/endophytic) (overall survival, P =0.003; recurrence-free survival, P <0.001), N (nearness) (overall survival, P =0.063; recurrence-free survival, P <0.001), A (anterior/posterior) (overall survival, P <0.001; recurrence-free survival, P =0.005), L (location) (overall survival, P =0.008; recurrence-free survival, P <0.001) and suffix 'h' (overall survival, P =0.237; recurrence-free survival, P =0.034). Kaplan-Meier curves of overall survival and recurrence-free survival rates were significantly different when stratified by radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score complexity group (overall survival, P <0.001; recurrence-free survival, P <0.001). After adjusting for tumour stage and grade, radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score as continuous variables was an adverse independent risk factor for survival outcomes [P =0.027, hazard ratio (95% confidence interval)=1.151 (1.016-1.303)] and recurrence-free survival [P <0.001, hazard ratio (95% confidence interval)=1.299 (1.125-1.501)]. For tumours with radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores of 4 and 5, partial nephrectomy showed a survival benefit than radical nephrectomy. Both components and complexity groups of the radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score are associated with survival outcomes in renal tumour patients.

Application of colony-stimulating factor 3 in determining the prognosis of high-grade gliomas based on magnetic resonance imaging radiomics

Rationale and objectivesRadiomics is a promising, non-invasive method for determining the prognosis of high-grade glioma (HGG). The connection between radiomics and the HGG prognostic biomarker is still insufficient. Materials and methodsIn this study, we collected the pathological, clinical, RNA-sequencing, and enhanced MRI data of HGG from TCIA and TCGA databases. We characterized the prognostic value of CSF3. Kaplan–Meier (KM) analysis, univariate and multivariate Cox regression, subgroup analysis, Spearman analysis, and gene set variation analysis enrichment were used to elucidate the prognostic value of the CSF3 gene and the correlation between CSF3 and tumor features. We used CIBERSORT to analyze the correlation between CSF3 and cancer immune infiltrates. Logistic regression (LR) and support vector machine methods (SVM) were used to build the radiomics models for the prognosis prediction of HGG based on the expression of CSF3. ResultsBased on the radiomics score calculated from LR model, 182 patients with HGG from TCGA database were divided into radiomics score (RS) high and low groups. CSF3 expression varied between tumor and normal group tissues. CSF3 expression was found to be a significant risk factor for survival outcomes. A positive association was found between CSF3 expression and immune infiltration. The radiomics model based on both LR and SVM methods showed high clinical practicability. ConclusionThe results showed that CSF3 has a prognostic value in HGG. The developed radiomics models can predict the expression of CSF3, and further validate the predictions of the radiomics models for HGG.

Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation from Different Donor Types in Primary Refractory Acute Myeloid Leukemia: A Report from the ALWP of the EBMT

Background Primary refractory acute myeloid leukemia (prAML) is a poor prognosis disease for which allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative option currently available. We aimed to estimate outcomes in the recent period, to analyze how different donor types may have impacted survival outcomes and to identify the most relevant predictive factors for allo-HSCT in prAML. Methods We conducted a retrospective multicenter study of adult patients reported to the European Society for Blood and Marrow Transplantation (EBMT) registry who received an allo-HSCT between 2015 and 2020 for prAML. We considered HSCT performed from matched sibling donors (MSD), 10/10 unrelated donors (UD 10/10), 9/10 unrelated donors (UD 9/10) and haploidentical donors. Primary endpoint was leukemia-free survival (LFS), secondary endpoints were overall survival (OS), relapse incidence (RI) and non-relapse mortality (NRM). A Cox proportional hazards model was used for multivariate analysis. Results We included 1574 patients. Median age was 56.9 years (range 18.1-77.9). Cytogenetic risk was intermediate in 855 (54.3%), adverse in 679 (43.2%) and favorable in 40 (2.5%) patients. Donor type was distributed as follows: MSD n = 521 (33.1%), UD 10/10 n = 540 (34.3%), UD 9/10 n = 153 (9.7%), haploidentical n = 360 (22.9%). Table 1 summarizes patient and transplant characteristics. Patients allografted from an MSD were younger, allografted faster after diagnosis, more often received myeloablative conditioning (MAC) (details in Table 1) and had less secondary AML. Use of post-transplant cyclophosphamide, and bone marrow as a stem cell source were more frequent in haploidentical transplants. LFS at 2 years was significantly lower in haploidentical transplants (27% [95%CI: 22-32.2]) compared to MSD (35.2% [95%CI: 30.6-39.9]), to UD 10/10 (37.6% [95%CI: 33.2-42.1]) and to UD 9/10 (35.2% [95%CI: 27.1-43.5]) (p=0.003). Haploidentical transplants also showed inferior OS at 2 years: 31.2% (95%CI: 25.8-36.8) compared to 40.9% (95%CI: 35.9-45.8) in MSD, to 45.7% (95%CI: 41.1-50.2) in UD 10/10 and to 43% (95%CI: 34.5-51.3) in UD 9/10 (p=0.001). In the UD 9/10 group we observed the lowest RI (33.5% [95%CI: 25.6-41.6], 46.7% [95%CI: 41.8-51.4] in MSD, 42.7% [95%CI: 38.2-47.1] in UD 10/10, 46.8% [95%CI: 41.1-52.3] in haploidentical) (p=0.013), and the highest NRM (31.2% [95%CI: 23.6-39.2], 18.1% [95%CI: 14.6-21.9] in MSD, 19.7% [95%CI: 16.3-23.3] in UD 10/10, 26.2% [95%CI: 21.6-31.1] in haploidentical) (p=0.001). Of note, LFS at 2 years was reduced for adverse cytogenetic risk (26.1% for adverse, 39.8% for intermediate and 51.9% for favorable risk) (p=0.001) and significantly differed between reduced intensity conditioning (RIC) and MAC (37.4% and 29.8%, respectively) (p=0.033). In multivariate analysis, factors predicting poor LFS were haploidentical donor (hazard ratio [HR] 1.22 [95%CI: 1.01-1.48], p=0.043), adverse cytogenetic risk (HR 1.73 [95%CI: 1.51-1.99], p<0.0001) and time from diagnosis to HSCT (HR 1.03 [95%CI: 1.01-1.06], p=0.009), whereas factors associated with a better LFS were RIC conditioning (HR 0.85 [95%CI: 0.73-0.98], p=0.025) and good Karnofsky performance status (KPS) ≥ 80 (HR 0.74 [95%CI: 0.62-0.88], p=0.0009). Haploidentical transplant correlated with lower OS (HR 1.3 [95%CI: 1.06-1.61], p=0.014) and higher NRM (HR 1.69 [95%CI: 1.18-2.41], p=0.004) and adverse cytogenetic risk was associated with higher RI (HR 1.9 [95%CI: 1.6-2.24], p<0.0001), higher NRM (HR 1.47 [95%CI: 1.15-1.87], p=0.002) and lower OS (HR 1.82 [95%CI: 1.57-2.11], p<0.0001). Moreover, increased age predicted higher NRM (HR 1.31 [95%CI: 1.17-1.47], p<0.0001) and lower OS (HR 1.09 [95%CI: 1.02-1.16], p=0.006). Conclusions Our study identified risk factors for survival outcomes in the challenging setting of allo-HSCT for prAML. The most relevant factors are adverse cytogenetic risk and haploidentical donor, both associated with worse outcomes. Of note, the group of haploidentical transplants presented the highest rate of bone marrow used as a stem cell source, with a possible impact on survival outcomes. Longer time from diagnosis to HSCT negatively impacted LFS, whereas use of RIC and KPS ≥ 80 showed a higher LFS. As concerns secondary endpoints, unrelated donors achieved better OS compared to other donors, and UD 9/10 showed the lowest RI at the expense of the highest NRM. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Effects of gross tumor volume and radiation dose on survival and locoregional recurrence in early-stage extranodal NK/T-cell lymphoma treated with intensity-modulated radiation therapy.

To investigate the prognostic value of gross tumor volume (GTV) in early-stage extranodal NK/T-cell lymphoma (ENKTCL) treated with intensity-modulated radiation therapy (IMRT) and explore the interactive effect of GTV and radiotherapy (RT) dose on locoregional recurrence (LRR). The data of 319 early-stage ENKTCL patients who underwent IMRT were reviewed retrospectively. Overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) were estimated using Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards regression was performed to identify independent risk factors for survival outcomes. Penalized spline regression was used to flexibly model the association of continuous predictors (GTV and RT dose) with mortality, progression, and relapse. The 5-year OS, PFS, and LRC for the entire cohort were 72.9, 64.4, and 89.9%, respectively. The risks of disease mortality, progression, and recurrence increased steadily with increasing GTV. Patients with GTV < 35mL had significantly higher 5-year OS (83.0% vs. 59.4%; P < 0.001), PFS (76.7% vs. 48.4%; P < 0.001), and lower 5-year cumulative LRR rate (4.9% vs. 14.5%; P = 0.004), than patients with GTV ≥ 35mL. The risk of LRR was low with RT doses of 50-56Gy, independent of GTV. For patients with GTV ≥ 35mL, dose ≥ 56Gy was not associated with decreased LRR. Larger GTV is associated with worse survival and higher LRR in early-stage ENKTCL patients treated with IMRT. A dose of 50-56Gy may be appropriate to achieve lower risk of LRR, regardless of GTV.

N6-methyladenosine long non-coding RNAs reveal novel tool to implicate overall survival and immune microenvironment in renal clear cell carcinoma.

This study aimed to investigate whether N6-methyladenosine (m6A)-related long non-coding RNAs (m6ARelncRNAs) could provide novel tools to predict overall survival of renal clear cell carcinoma. The transcriptomic data and clinical information of patients with renal clear cell carcinoma from The Cancer Genome Atlas (TCGA) were analysed. Distinct m6A modification patterns were systemically analysed via consensus clustering analysis. An m6ARelncRNA signature was constructed in the training cohort using the least absolute shrinkage and selection operator (LASSO) analysis and validated in the test cohort. Potential predictive accuracy of the signature was further assessed via Kaplan-Meier survival, univariate and multivariate Cox regression and subgroup analyses. The Tumour Immune Dysfunction and Exclusion (TIDE) algorithm was used to investigate the role of m6ARelncRNAs in guiding immunotherapy for patients with renal carcinoma. An m6ARelncRNA signature based on only six lncRNAs was successfully constructed. The high-risk group derived from this signature had significantly poorer overall survival in both training and test cohorts (p < 0.001). Independent prognostic analysis further revealed that m6ARelncRNA risk (p < 0.01) was an independent risk factor for survival outcomes of renal carcinoma. TIDE algorithm revealed that immunotherapy response was poorer in the high-risk group than in the low-risk group. Drug sensitivity analysis based on IC50 revealed that high-risk patients were potentially sensitive to various anti-tumour drugs, including bortezomib, cisplatin, docetaxel, etoposide and sunitinib. m6ARelncRNAs provide novel tools that can be used to predict overall survival and examine the immune microenvironment of renal clear cell carcinoma.

Long-term follow-up of haploidentical transplantation in relapsed/refractory severe aplastic anemia: a multicenter prospective study

In recent decades, haploidentical stem cell transplantation (haplo-SCT) to treat severe aplastic anemia (SAA) has achieved remarkable progress. However, long-term results are still lacking. We conducted a multicenter prospective study involving SAA patients who underwent haplo-SCT as salvage therapy. Long-term outcomes were assessed, mainly focusing on survival and quality of life (QoL). Longitudinal QoL was prospectively evaluated during pretransplantation and at 3 and 5 years posttransplantation using the SF-36 scale in adults and the PedsQL 4.0 scale in children. A total of 287 SAA patients were enrolled, and the median follow-up was 4.56 years (range, 3.01–9.05 years) among surviving patients. During the long-term follow-up, 268 of 275 evaluable patients (97.5%) obtained sustained full donor chimerism, and 93.4% had complete hematopoietic recovery. The estimated overall survival and failure-free survival for the whole cohort at 9 years were 85.4% ± 2.1% and 84.0% ± 2.2%, respectively. Age (≥18 years) and a poorer performance status (ECOG >1) were identified as risk factors for survival outcomes. For QoL recovery after haplo-SCT, we found that QoL progressively improved from pretransplantation to the 3-year and 5-year time points with statistical significance. The occurrence of chronic graft versus host disease was a risk factor predicting poorer QoL scores in both the child and adult cohorts. At the last follow-up, 74.0% of children and 72.9% of adults returned to normal school or work. These inspiring long-term outcomes suggest that salvage transplantation with haploidentical donors can be routine practice for SAA patients without human leukocyte antigen (HLA)-matched donors.

Identification and Validation of PLOD2 as an Adverse Prognostic Biomarker for Oral Squamous Cell Carcinoma.

Background: Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a key enzyme that catalyzes the hydroxylation of lysine, plays a crucial role in the progression of several solid tumors. However, its spatial expression profile and prognostic significance in oral squamous cell carcinoma (OSCC) have not been revealed. Materials: Mass spectrometry was used to explore amino acid perturbations between OSCC tumor tissues and paired normal tissues of 28 patients. Then, PLOD2 mRNA and protein levels were assessed using several public databases and 18 pairs of OSCC patients’ tissues. Additionally, PLOD2 spatial expression profiles were investigated in 100 OSCC patients by immunohistochemistry and its diagnostic and prognostic values were also evaluated. Lastly, gene set enrichment analysis (GSEA) was used to investigate the potential functions of PLOD2 in OSCC. Results: Lysine was significantly elevated in OSCC tissues and could effectively distinguish tumor from normal tissues (AUC = 0.859, p = 0.0035). PLOD2 mRNA and protein levels were highly increased in tumor tissues of head and neck squamous cell carcinoma (HNSCC) (p < 0.001) and OSCC compared with those in nontumor tissues (p < 0.001). Histopathologically, PLOD2 was ubiquitously expressed in tumor cells (TCs) and fibroblast-like cells (FLCs) of OSCC patients but absent in tumor-infiltrating lymphocytes (TILs). Patients with highly expressed PLOD2 in TCs (PLOD2TCs) and FLCs (PLOD2FLCs) showed poor differentiation, a worse pattern of invasion (WPOI) and more lymph node metastasis (LNM), contributing to higher postoperative metastasis risk and poor survival time. However, PLOD2FLCs rather than PLOD2TCs was an independent risk factor for survival outcomes in OSCC patients. Molecularly, GSEA demonstrated highly expressed PLOD2 was mainly enriched in epithelial–mesenchymal transformation (EMT), TGF-beta signaling and hypoxia pathway, which are associated with poor clinical outcomes of OSCC patients. Conclusions: PLOD2 was a poor prognostic biomarker for OSCC patients and may affect the metastasis of OSCC through EMT pathway. These findings might shed novel sights for future research in PLOD2 targeted OSCC therapy.

Prognostic implication of PD-L1 polymorphisms in non-small cell lung cancer treated with radiotherapy.

BackgroundTo investigate the impact of programmed death‐ligand 1 (PD‐L1) polymorphisms on the prognosis of non‐small cell lung cancer (NSCLC) patients treated with curative radiotherapy.MethodsFour single nucleotide polymorphisms (SNPs) (rs822336G>C, rs822337T>A, rs822338C>T, and rs2297136A>G) in the PD‐L1 gene were evaluated in 124 NSCLC patients. Clinical stage was I in 28, II in 17, and III in 79 patients. Fifty‐seven patients received radiotherapy alone, including 28 patients who received stereotactic body radiotherapy. Sixty‐seven patients received sequential or concurrent chemoradiotherapy. Risk factors for survival outcomes were analyzed with the log‐rank test and multivariate Cox proportional hazards models.ResultsThe rs822336GC+CC genotype was associated with better overall survival (OS) (hazard ratio [HR] = 0.60, 95% confidence interval [CI] = 0.37–0.97, p = 0.036) and regional failure‐free survival (RFFS) (HR = 0.32, 95% CI = 0.14–0.76, p = 0.009), compared with rs822336GG genotype. The rs822337TA+AA genotype was associated with better OS (HR =0.54, 95% CI = 0.34–0.88, p = 0.014), progression‐free survival (PFS) (HR = 0.64, 95% CI = 0.41–0.99, p = 0.046), and RFFS (HR = 0.38, 95% CI = 0.17–0.81, p = 0.013), compared with rs822337TT genotype. Three SNPs (rs822336, rs822337, and rs822338) were in linkage disequilibrium. Combined GTC and GTT (GT*) haplotype was associated with significantly worse OS (p = 0.018), PFS (p = 0.044), and RFFS (p = 0.038), compared with those with other combined haplotypes. Patients with diplotypes of two GT* haplotypes showed significantly worse OS (p = 0.023) and RFFS (p = 0.014) than those with other diplotypes.ConclusionsThese findings suggest that PD‐L1 polymorphisms could be predictive markers for NSCLC patients receiving radiotherapy.

Recurrent colorectal liver metastasis patients could benefit from repeat hepatic resection

BackgroundLocal treatment remains the best option for recurrent colorectal liver metastasis (CRLM). The current study aimed to investigate predictive factors of survival outcomes and select candidates for local treatment for CRLM at first recurrence.MethodsData were collected retrospectively from CRLM patients who underwent hepatic resection and developed first recurrence between 2000 and 2019 at our institution. A nomogram predicting overall survival was established based on a multivariable Cox model of clinicopathologic factors. The predictive accuracy and discriminative ability of the nomogram were determined by the concordance index and calibration curve.ResultsAmong 867 patients who underwent curative hepatic resection, 549 patients developed recurrence. Three hundred patients were evaluated and had resectable and liver-limited disease. Among them, repeat liver resection and percutaneous radiofrequency ablation were performed in 88 and 85 patients, respectively. The other 127 patients received only systemic chemotherapy. Multivariable analysis identified primary lymph node positivity, tumor size > 3 cm, early recurrence, RAS gene mutation and no local treatment as independent risk factors for survival outcomes. Integrating these five variables, the nomogram presented a good concordance index of 0.707. Compared with patients who received only systemic chemotherapy, radical local treatment did not significantly improve survival outcomes (median OS: 21 vs. 15 months, p = 0.126) in the high-risk group (total score ≥ 13).ConclusionRadical local treatment improved the survival of recurrent CRLM patients. The proposed model facilitates personalized assessments of prognosis for patients who develop first recurrence in the liver.

Prognostic value of preoperative body mass index for diabetic patients with non-metastasis gastric cancer: a single center experience

AimThis study was designed to investigate the prognostic effect of preoperative body mass index (BMI) for Type 2 diabetes mellitus (T2DM) patients with non-metastasis gastric cancer (GC) who underwent D2 gastrectomy.MethodsT2DM patients with pT1–4bN0–3bM0 GC were retrospectively collected in Department of Gastrointestinal Surgical Oncology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital from January, 2000 to December, 2010. These patients underwent D2 radical resection of the stomach combined with regional lymphadenectomy. Chi-square test was used to analyze unordered categorical variables and ranked data, followed by Kaplan–Meier analysis as well as Cox regression models to detect risk factors for survival outcomes. In addition, the cut-off point was determined by the X-tile program. All analyses were carried out using survival package of R and SPSS Software.ResultsA total of 302 T2DM patients with pT1–4bN0–3bM0 GC were collected and analyzed. The cut-off points of BMI, identified by the X-tile program, was 19 kg/m2. Patients with low BMI (< 19 kg/m2) had a higher percentage of advanced T stage (T4a and T4b), more advanced TNM stage (stage IIIA, IIIB and IIIC), and more elevated level of serum carcinoembryonic antigen (CEA), compared to those with high BMI (> 19 kg/m2) (all P < 0.05). In the low BMI subgroup, the 5-year overall survival rate was 39.02%, which was as high as 58.11% in the high BMI subgroup (P < 0.05). In the multivariate Cox regression model revealed that IIIC stage (OR = 3.101), N3b stage (OR = 3.113) were the most important prognostic indicators, followed by pretreatment BMI (OR = 2.136).ConclusionLow preoperative BMI (< 19 kg/m2) was a poor prognostic marker for T2DM patients with pT1–4bN0–3bM0 GC.

The log odds of positive lymph nodes predicts survival of advanced stage endometrial cancer: a retrospective analysis of 3230 patients in the SEER database

The log odds of positive lymph nodes predicts survival of advanced stage endometrial cancer: a retrospective analysis of 3230 patients in the SEER database

Perioperative risk factors for survival outcomes in elective colorectal cancer surgery: a retrospective cohort study

BackgroundSurgical resection remains the best option for long-term survival in colorectal cancer (CRC); however, surgery can lead to tumor cell release into the circulation. Previous studies have also shown that surgery can affect cancer cell growth. The role of perioperative factors influencing long-term survival in patients presenting for CRC surgery remains to be investigated.MethodsThis retrospective single–center cohort study was conducted to collect the clinical data of patients who underwent elective laparoscopic resection for CRC from January 2014 to December 2015, namely clinical manifestations, pathological results, and perioperative characteristics. Survival was estimated using the Kaplan–Meier log-rank test. Univariable and multivariable Cox regression models were used to compare hazard ratios (HR) for death.ResultsA total of 234 patients were eligible for analysis. In the multivariable Cox model, tumor-node-metastasis (TNM) stage (stage IV: HR 30.63, 95% confidence interval (CI): 3.85–243.65; P = 0.001), lymphovascular invasion (yes: HR 2.07, 95% CI 1.09–3.92; P = 0.027), inhalational anesthesia with isoflurane (HR 1.96, 95% CI 1.19–3.21; P = 0.008), and Klintrup–Makinen (KM) inflammatory cell infiltration grade (low-grade inflammation: HR 2.03, 95% CI 1.20–3.43; P = 0.008) were independent risk factors affecting 5-year overall survival after laparoscopic resection for CRC.ConclusionsTNM stage, lymphovascular invasion, isoflurane, and KM grade were independent risk factors affecting CRC prognosis. Sevoflurane and high-grade inflammation may be associated with improved survival in CRC patients undergoing resection.

The clinical significance of microvascular invasion in the surgical planning and postoperative sequential treatment in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common and most lethal malignant tumors in the world. Microvascular invasion (MVI) is a major risk factor for survival outcomes and intrahepatic metastasis after resection in patients with HCC. Relevant English literatures retrieved using PubMed on the research progress of MVI in patients with HCC were reviewed. For HCC patients, especially those with MVI, it is very important to develop a comprehensive and sequential treatment plan to support the long-term survival of patients. This manuscript reviewed and analyzed the risk factors for MVI; the preoperative prediction of MVI, which informs the selection of surgical strategies; and the current situation and future direction of comprehensive postoperative treatment strategies; to provide a basis for the comprehensive treatment of HCC patients with MVI. For HCC patients with MVI, the preoperative prediction of MVI may play a certain guiding role in planning procedures, and the comprehensive sequential postoperative pathological detection of HCC MVI may provide a basis for treatment decisions.

Predictive value of preoperative lymphocyte-to-monocyte ratio on survival outcomes in bladder cancer patients after radical cystectomy.

Purpose: To determine the prognostic significance of the pre-operative lymphocyte-to-monocyte (LMR) in patients with bladder cancer (BCa) who underwent radical cystectomy (RC), and to assess its prognostic benefit compared to models relying solely on clinicopathological factors.Materials and Methods: A retrospective analysis of the 342 BCa patients undergoing RC at our institution from 2004 to 2017 was conducted to assess LMR prognostic significance. Overall survival (OS) and cancer-specific survival (CSS) were assessed using the Kaplan-Meier method. Cox regression models identified risk factors for survival outcomes. Two new models were developed based on basal models to predict OS and CSS at 1, 3, and 5 years after RC. The accuracy of the new models was evaluated using receiver operating characteristic curves as well as the concordance index. We also conducted decision curve analysis (DCA) to assess their net benefit.Results: An association between excellent long-term patient survival outcomes and higher LMR levels was observed. The median OS and CSS for higher LMR level in patients was 98.8 months and >120 months, respectively. Cox regression multivariate analysis showed that pre-operative LMR, as a continuous variable, was an independent survival outcome predictor (p<0.001). The utilization of LMR in the standard model resulted in significant discriminatory improvement in OS (5.6%, p<0.001) and CSS (4.9%, p=0.001) prediction. Moreover, as shown in DCA, utilization of the new model, including LMR, resulted in a net benefit compared to base models for predicting OS and CSS at 1, 3, and 5 years.Conclusions: An independent association was observed between higher pre-operative LMR in BCa patients undergoing RC and significantly better OS and CSS. In addition, a significant improvement in predictive accuracy was observed with LMR inclusion in multiparametric prediction tools. Therefore, LMR may be utilized in pre-operative patient risk stratification to assist in patient counseling and clinical decision making.

A new classification for hepatocellular carcinoma with hepatic vein tumor thrombus.

Hepatic vein tumor thrombus (HVTT) is a significant poor risk factor for survival outcomes in hepatocellular carcinoma (HCC) patients. Currently, the widely used international staging systems for HCC are not refined enough to evaluate prognosis for these patients. A new classification for macroscopic HVTT was established, aiming to better predict prognosis. This study included 437 consecutive HCC patients with HVTT who underwent different treatments. Overall survival (OS) and time-dependent receiver operating characteristic (ROC) curve area analysis were used to determine the prognostic capacities of the new classification when compared with the different currently used staging systems. The new HVTT classification was defined as: type I, tumor thrombosis involving hepatic vein (HV), including microvascular invasion; type II, tumor thrombosis involving the retrohepatic segment of inferior vena cava; and type III, tumor thrombosis involving the supradiaphragmatic segment of inferior vena cava. The numbers (percentages) of patients with types I, II, and III HVTT in the new classification were 146 (33.4%), 143 (32.7%), and 148 (33.9%), respectively. The 1-, 2-, and 3-year OS rates for types I to III HVTT were 79.5%, 58.6%, and 29.1%; 54.8%, 23.3%, and 13.8%; and 24.0%, 10.0%, and 2.1%, respectively. The time-dependent-ROC curve area analysis demonstrated that the predicting capacity of the new HVTT classification was significantly better than any other staging systems. A new HVTT classification was established to predict prognosis of HCC patients with HVTT who underwent different treatments. This classification was superior to, and it may serve as a supplement to, the commonly used staging systems.

Abstract 6519: Patient, primary colorectal tumor and liver metastases factors which influence survival after liver metastasectomy and therefore should be considered at the preoperative tumor board

Abstract Aim of the study: Patients with colorectal liver metastases (CRLM) should be considered for liver surgery and this study illuminate important factors to be considered at the preoperative multidisciplinary tumor board. Background: Survival after surgical resection or ablation of colorectal liver metastases is increasingly favorable but only a minority of patients undergo curatively intended treatment. Several studies have shown the importance of assessing resectability by liver surgeons. Which prognostic factors to consider before liver surgery is not fully understood. Methods: The Swedish colorectal cancer registry (SCRCR) and the Swedish registry for liver tumors (SweLiv) were linked to identify radically resected primary colorectal cancer patients during the years 2009-2013 also surgically treated for liver metastases, synchronously or metachronously. CRLM characteristics and treatment strategies as well as primary tumor and patient factors were analyzed for prognostic impact. 5-year age-standardized relative survival (RS) and 5-year excess mortality rate ratio (EMRR) were calculated. Treatment with ablation only for tumors with maximum size of 30 mm was analyzed in a propensity score weighted cox regression. Results: 1325 patients were included in the study cohort, whereof 300 were 75 years or older. 1200 were treated with resection and 125 were treated with ablation only. Age-standardized relative five-year survival after open resection of colorectal liver metastases was 54.8 % (95 % CI: 50.6-58.7) and after ablation 32.4 % (95 % CI: 23.3-41.9). Multivariate analysis identified age ≥75 years, tumor size &amp;gt;20 mm, location in segment 4, 6, 7 or 8, multiple metastatic sites and progress after chemotherapy as important risk factors with more than 25 % higher EMRR. Only when analyzed without segments included in the multivariate model was the number of metastases a significant risk factor. Vascular invasion, lymph node ratio and complications at time of primary tumor resection were also important negative prognostic factors. Ablation of small metastases compared to resection was a significant risk factor (HR 2.25 (95 % CI 1.61-3.15)). Conclusion: Tumor size over 20 mm and location of metastases as well as lymph node status and complications after resection of the primary tumor are important risk factors for survival outcome after liver surgery of CRLM. Progress after preoperative chemotherapy and ablation compared to resection more than doubled the risk of death within 5 years. Citation Format: Peter Scherman, Peter Naredi, Ingvar Syk, Erik Holmberg, Magnus Rizell. Patient, primary colorectal tumor and liver metastases factors which influence survival after liver metastasectomy and therefore should be considered at the preoperative tumor board [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6519.

Computed Tomography-Guided Percutaneous Cryoablation for ‎ Subcardiac Hepatocellular Carcinoma: Safety, Efficacy, Therapeutic Results and Risk Factors for Survival Outcomes.

ObjectiveTo investigate the clinical safety, efficacy, therapeutic outcomes and risk factors of computed tomography-guided percutaneous cryoablation (CT-PCRA) for subcardiac hepatocellular carcinoma (HCC).Patients and MethodsIn this study, patients with single HCC nodules located on the left lobe who subsequently underwent CT-PCRA were reviewed from July 2012 to August 2016. According to the definition of subcardiac HCC, the patients were grouped into the subcardiac HCC group (n=33) and the non-subcardiac HCC group (n=40). The technical success rates, tumour response rates, oncological outcomes including overall survival (OS) and recurrence-free survival (RFS) and complications were compared. Multivariate analysis was performed on clinicopathological variables to identify factors affecting long-term outcomes.ResultsSeventy-three patients with subcardiac HCC were included in this study. After a median follow-up time of 37.8 months, 27.4% (20/73) of the patients died. The technical success and complete response rates were not significantly different between the two groups (p = 1.000; p = 0.590). The cumulative OS and RFS of the subcardiac HCC group were comparable to those of the non-subcardiac HCC group (p =0.820, p =0.922). Two major complications, intra-abdominal bleeding and right pleural effusion, were found at 2.2 and 3.1 months in the subcardiac HCC group, which were comparable with those in the non-subcardiac HCC group (p = 0.683). The multivariate analysis results showed that older age (hazard ratio [HR]: 2.382, 95% confidence interval [CI]: 1.884–7.823; p = 0.038) and ALBI grade 2–3 (HR: 3.398, 95% CI: 1.950–6.058; p = 0.021) may be predictors of poor OS and that tumour size ≥3 cm in diameter (HR: 3.302, 95% CI: 2.232–8.293; p = 0.012) may be a predictor of poor RFS.ConclusionCT-PCRA for subcardiac HCC can be performed safely and efficiently and contribute to improving survival prognosis.

Nomograms to predict survival outcomes after microwave ablation in elderly patients (>65 years old) with early-stage hepatocellular carcinoma

Objectives To develop and validate the nomograms to predict survival outcomes after microwave ablation (MWA) in elderly patients(>65 years old) with early-stage hepatocellular carcinoma (EHCC). Methods This retrospective study was approved by the institutional review board. A total of 265 EHCC patients (76 females, 189 males; average age 71.4 years ± 5.4 [standard deviation]) with 345 nodules subsequently underwent MWA from April 2006 to October 2019. Baseline characteristics were collected to identify the risk factors for the determination of survival outcomes after MWA. The nomograms were based on prognostic factors for overall survival (OS) and recurrence-free survival (RFS) from the multivariate Cox proportional hazards model and validated in external cohorts from another two institutions (n = 130). The nomograms were assessed for their predictive accuracy using Harrell’s concordance index (C-index). Results After a median follow-up time of 28.6 months, 29.8% (79/265) of the patients died, and 54.3% (144/265) of the patients experienced recurrence in the training set. The OS nomogram was developed based on the hepatitis B virus (HBV) presence, α-fetoprotein (AFP), and albumin, with a C-index of 0.757 (95% confidence interval [CI]: 0.645, 0.789).The scores of the nomogram ranged from 0 to 24. The RFS nomogram was developed based on tumor number, abutting major vessels and platelets, with a C-index of 0.733 (CI: 0.672, 0.774). The likelihood of 3- and 5-year OS and RFS were consistent between clinical observations and nomogram predictions in external cohorts. Conclusions The nomogram models can be useful in determining the risk of OS and RFS in elderly patients with EHCC after MWA, which can guide individual patient management. Key points MWA is an effective and feasible treatment for elderly patients with EHCC and can improve survival outcomes. A calibrated and objective nomogram model for the prediction of survival outcomes in elderly patients (>65 years old) may guide patient selection and MWA treatment. Older age was not deemed to be a risk factor for survival outcomes when the elderly patients with EHCC underwent MWA.

Prognostic factors for patients with chondrosarcoma: A survival analysis based on the Surveillance, Epidemiology, and End Results (SEER) database (1973–2012)

Current reports on prognostic factors for chondrosarcoma mainly involve patients in treatment centers. Few are based on multicenter or multi-eras. We analyzed existing data from the Surveillance, Epidemiology, and End Results (SEER) database to investigate the risk factors for survival outcomes. All patients with chondrosarcoma from 1973 to 2012 were identified. 3737 patients were eligible and included. In survival analysis, patient had good survival outcome if the patient was female, young, with localized stage, well grade, small tumor size, treated with surgery, while patient was male, old, with distant stage, undifferentiated grade, tumor size <50 mm, located in vertebral or pelvic bones, underwent radiation had bad survival outcome. Surgery types from having best survival outcomes to worst were local excision, radical excision, amputation, no surgery. ‘Well’ and ‘moderately’ grade seems to be suitable for local excision, but ‘poorly’ and ‘undifferentiated’ grade suitable for wide local excision. Multivariate COX regression analysis showed year of diagnosis, sex, age of diagnosis, stage, grade, tumor site, surgery, radiation were independent risk factors. Year of diagnosis, sex, age of diagnosis, stage, grade, tumor site, surgery, radiation were independent risk factors. Excision is a better treatment than amputation. Doctors can use wide local excision to treat chondrosarcoma, especially when encountering high grade chondrosarcoma or pelvic chondrosarcoma.