Independent Prognostic Factor For Recurrence-free Survival Research Articles

Subsolid Lung Adenocarcinomas: Radiological, Clinical and Pathological Features and Outcomes

Lung adenocarcinomas manifesting as subsolid nodules usually have a favorable prognosis. This study aimed to have a comprehensive investigation of the radiological and clinicopathologic features and oncological outcomes of subsolid nodules. Between March 2010 and December 2015, 865 patients with surgically resected clinical IA subsolid lung adenocarcinoma were retrospectively reviewed. Patients were classified into the pure ground-glass nodules (GGN) (pGGN [n=358], without solid component on lung and mediastinal windows), heterogeneous GGN (hGGN [n=65], only with solid components on lung window), and real part-solid nodule (rPSN [n=442], with solid component on both lung and mediastinal windows) groups. The clinicopathological features and survival time of the three groups were compared between groups. There was a significant increase in median tumor size (P < 0.001), solid component size measured at lung window (LW-SCS) (P < 0.001), and the proportion of invasive adenocarcinoma subtypes (P < 0.001) from pGGNs to hGGNs to rPSNs. After adjustment for LW-SCS, adenocarcinomas with predominant lepidic patterns were still more common in hGGNs than in rPSNs (P=0.009). Patients with rPSNs had a significantly worse recurrence-free survival (RFS) than those with pGGNs and hGGNs (5-year: 91.9% versus 100% versus 100%, P < 0.001). Multivariate Cox analyses revealed that gender (both P < 0.05) and clinical T category (based on lung window [LW-cT] [P=0.002] or mediastinal window [MW-cT] [P < 0.001]) were independent prognostic factors of RFS in the rPSN group. HGGNs represented as an intermediate subtype between pGGNs and rPSNs. Both pGGNs and hGGNs had excellent outcomes, while rPSNs exhibited a worse prognosis than them. Clinical T category and gender had prognostic implications for rPSNs.

Novel prognostic implications of YTH domain family 2 in resected hepatocellular carcinoma.

N6-methyladenosine (m6A), the most abundant internal RNA modification, serves a critical role in cancer development. However, the clinical implications of m6A in hepatocellular carcinoma (HCC) remain unclear. The present study sought to reveal the potential roles of m6A readers, which recognize m6A, in HCC. A total of 177 HCC and paired non-cancerous liver tissues from patients who underwent hepatectomy were analysed using quantitative PCR for the expression of m6A readers: YT521-B homology domain family 1 (YTHDF1) and YT521-B homology domain family 2 (YTHDF2). The expression levels of both YTHDF1 and YTHDF2 were not significantly different between tumour and non-cancerous tissues (P=0.93 and P=0.7, respectively). Analysis of the association between clinical features and m6A reader expression revealed that YTHDF1 expression was associated with formation of capsule (P=0.02), whereas low YTHDF2 expression was associated with septal formation (P=0.02). Furthermore, high YTHDF1 expression and high YTHDF2 expression were significantly associated with shorter recurrence-free survival (RFS) [YTHDF1: Mean survival time (MST), 34.0 vs. 19.0 months, P=0.014; YTHDF2: MST, 30.1 vs. 12.9 months, P=0.0032], whereas YTHDF1 and YTHDF2 expression was not significantly associated with overall survival (OS) (YTHDF1: MST, 99.4 vs. 70.2 months, P=0.74; YTHDF2: MST, 98.4 vs. 64.1 months, P=0.28). According to multivariate analysis, serosal invasion [hazard ratio (HR), 2.39; 95% CI 1.30–4.42; P=0.005), portal vein or hepatic vein invasion (HR, 2.82; 95% CI 1.26–6.28; P=0.01) and YTHDF2 expression in HCC tissues (HR, 1.85; 95% CI 1.09–3.15; P=0.02) were identified as significant independent prognostic factors for RFS. α-fetoprotein (HR, 1.79; 95% CI 1.10–2.92; P=0.02), serosal invasion (HR, 1.99; 95% CI 1.17–3.34; P=0.01) and portal vein or hepatic vein invasion (HR, 3.02; 95% CI 1.38–6.61; P=0.006) were identified as significant independent prognostic factors for OS. In conclusion, the present study revealed that high YTHDF2 expression, an m6A reader, in HCC tissues was associated with cancer recurrence.

Neutrophil Extracellular Traps and Macrophage Extracellular Traps Predict Postoperative Recurrence in Resectable Nonfunctional Pancreatic Neuroendocrine Tumors.

BackgroundExtracellular traps (ETs) and tumor-infiltrating immune cells can contribute to disease progression. The clinical significance of tumor-infiltrating neutrophils and macrophages and related extracellular traps in pancreatic neuroendocrine tumors (pNETs) has not been fully elucidated. This study aimed to explore the prognostic value of tumor infiltration and ET formation by neutrophils and macrophages in pNETs.MethodsA total of 135 patients with radical resection of nonfunctional pNETs were analyzed retrospectively. Immunohistochemistry and immunofluorescence were utilized to stain tumor tissue sections. The recurrence-free survival (RFS) of subgroups determined by Kaplan-Meier analysis was compared with the log-rank test. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. A nomogram was established to predict 3-year RFS.ResultsPatients with high tumor-infiltrating neutrophils or macrophages or positive expression of neutrophils ETs or macrophage ETs displayed worse RFS (all p<0.05). Moreover, univariate and multivariate Cox regression analyses showed that neutrophil and macrophage infiltration and ETs were independent prognostic factors for RFS (all p<0.05). A combined parameter including WHO grade, TNM stage, tumor-infiltrating neutrophils and macrophages, and neutrophil and macrophage ETs had the highest C-index (0.866) and lowest Akaike information criteria (326.557). The calibration plot of nomogram composed of the combined parameter exhibited excellent prognostic values for 3-year RFS.ConclusionsInfiltration and ETs by neutrophils and macrophages can be used as biological indicators of patient prognosis, suggesting the treatment potential for targeting those in nonfunctional pNETs.

Geriatric nutritional risk index predicts prognosis in hepatocellular carcinoma after hepatectomy: a propensity score matching analysis

The geriatric nutritional risk index (GNRI) is widely used for nutritional assessment in older inpatients and is associated with postoperative complications and cancer prognosis. We investigated the use of GNRI to predict long-term outcomes in hepatocellular carcinoma of all etiologies after hepatectomy. Overall, 346 patients were examined after propensity score matching. We dichotomized the GNRI score into high GNRI (> 98: N = 173) and low GNRI (≤ 98: N = 173) and evaluated recurrence-free survival (RFS) and overall survival (OS) between both groups. Clinicopathological characteristics between the low- and high-GNRI groups were similar after propensity score matching except for the components of the GNRI score (body mass index and serum albumin level), Child–Pugh score (comprising serum albumin level), and preoperative alpha-fetoprotein level (p < 0.0001, p < 0.0001, p = 0.0030, and p = 0.0007, respectively). High GNRI was associated with significantly better RFS and OS (p = 0.0003 and p = 0.0211, respectively; log-rank test). Multivariate analysis revealed that GNRI is an independent prognostic factor of RFS and OS (low vs. high; hazard ratio [HR], 1.8284; 95% confidence interval [CI] 1.3598–2.4586; p < 0.0001, and HR, 1.5452; 95% CI 1.0345–2.3079; p = 0.0335, respectively). GNRI is an objective, inexpensive, and easily calculated assessment tool for nutritional status and can predict prognosis of hepatocellular carcinoma after hepatectomy.

A novel risk factor panel predicts early recurrence in resected pancreatic neuroendocrine tumors.

Pancreatic neuroendocrine tumors (PanNETs) are indolent pancreatic tumors derived from neuroendocrine cells in pancreatic islets. To date, reliable predictors for identifying patients at high risk for recurrence after curative cancer resection are lacking. We aimed to determine independent predictors for high-risk PanNETs and patient outcomes after surgery. We analyzed relevant clinicopathological parameters in 319 consecutive patients of derivation cohort 1 and 106 patients of validation cohort 2 who underwent pancreatectomy and were diagnosed with PanNETs. Association of tumor characteristics with recurrence-free survival (RFS) and overall survival (OS) was evaluated using Cox regression. PanNET grade 3 (G3), pancreatic duct dilatation, and perineural invasion were independent prognostic factors for RFS and were significantly associated with early recurrence (within 1.5years) of PanNETs after curative resection (P = 0.019, P < 0.001, and P < 0.001, respectively). Using these factors, we established a novel risk factor panel (R-panel), which predicted early recurrence (P < 0.001, HR = 15.02, 95% CI 5.76-39.19). Predictive accuracy of this R-panel was favorable, with a C-index of 0.853, higher than AJCC TNM staging (0.713). We further built an integrated staging system combining R-panel scoring and TNM staging, which improved predictive probability of TNM staging. Finally, we showed that adjuvant therapy with long-acting somatostatin analogs (SSAs) significantly reduced postoperative recurrence (P < 0.001) and prolonged long-term survival (P = 0.021) in patients with the above risk factors. We identified a novel risk factor panel, which includes PanNET G3, pancreatic duct dilatation, and perineural invasion; this panel predicted early recurrence of PanNETs after curative resection. Patients with these risk factors can benefit from adjuvant therapy with SSAs.

Prognostic value of metabolic tumor volume and total lesion glycolysis on preoperative 18F-FDG PET/CT in patients with localized primary gastrointestinal stromal tumors

BackgroundThis study aimed to evaluate the prognostic value of pretreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with localized primary gastrointestinal stromal tumors (GISTs) and to compare the predictive values of 18F-FDG PET/CT parameters with those of clinicopathological prognostic factors.MethodsSixty-two localized GIST patients who underwent staging with 18F-FDG PET/CT from January 2007 to December 2013 before surgery were retrospectively enrolled. A volume of interest with a standardized uptake value (SUV) threshold of 2.5 was used to determine the metabolic tumor volume (MTV) and total lesion glycolysis (TLG). These metabolic indices, along with the maximum SUV (SUVmax), were analyzed to evaluate recurrence-free survival (RFS). Other significant clinical and pathologic indices were also retrospectively reviewed for RFS analysis.ResultsPatients were followed up for a median of 42.0 months (range, 5.6–111.5). During the follow-up period, 13 patients (21.0%) experienced disease recurrence. In univariate analysis, tumor size (> 5 cm), mitotic count (> 5/high-power field), modified National Institutes of Health (NIH) consensus criteria, adjuvant imatinib treatment, SUVmax (≥ 7.04), MTV (≥ 50.76 cm3), and TLG (≥ 228.79 g) were significant prognostic factors affecting RFS (p < 0.05). In multivariate analysis, only MTV (hazard ratio, 17.69; 95% confidence interval [CI], 2.03–154.17, p = 0.009) and TLG (hazard ratio, 20.48; 95% CI, 2.19–191.16, p = 0.008) were independent prognostic factors for RFS. The 5-year RFS rates were 96.4% and 96.6% in patients with a low MTV and TLG and 27.3% and 23.6% in patients with a high MTV and TLG, respectively (p < 0.001).ConclusionMTV and TLG are independent prognostic factors for predicting recurrence in patients with localized primary GIST. Patients with a high MTV or TLG are at risk for poor prognosis and should be closely observed for disease recurrence.

Timing to achieve the best recurrence-free survival after neoadjuvant chemoradiotherapy in locally advanced rectal cancer: experience in a large-volume center in China.

To identify the optimal interval from the end of neoadjuvant chemoradiotherapy to surgery (CRT-surgery interval) based on long-term oncological outcome of locally advanced rectal cancer (LARC). Retrospective data analysis is reported from patients diagnosed with cT3 or T4 or TxN+ rectal cancer who underwent neoadjuvant treatment and curative-intent surgery between January 2010 and December 2018. With a priority focus on the effect of interval on oncological prognosis, we used recurrence-free survival (RFS) as the primary endpoint to determine the best cutoff point of time intervals. Then, the short-term and long-term outcomes of patients from longer and shorter interval groups were compared. Data from 910 patients were analyzed, with 185 patients who achieved pCR (20.3%). The trend for increased rates of pCR for groups with a prolonged time interval was not observed (P = 0.808). X-tile determined a cutoff value of 10.5 weeks, and the population was divided into longer (> 10 weeks) and shorter (≤ 10 weeks) interval groups. The shorter interval was associated with a higher wound infection rate (4.7% vs. 1.1%, P = 0.031), but other postoperative complications did not differ between the groups. The 5-year RFS rate was significantly higher in patients in a longer group than those in the shorter weeks group (86.8% vs. 77.8%, P = 0.016). The 5-year OS rates between groups were similar (84.1% vs. 82.5%, P = 0.257). Local recurrence and lung metastases rates were higher in shorter interval group than those of longer group (local recurrence rate: 1.7% vs. 5.1%, P = 0.049; lung metastases rate: 5.7% vs. 10.7%, P = 0.047). Cox multivariate regression analysis confirmed the CRT-surgery interval (HR = 0.599, P = 0.045) to be an independent prognostic factor of RFS. This study is the first, to the best of our knowledge, to define the optimal CRT-surgery interval based on RFS as the primary endpoint. Prolonging the waiting period to 10 weeks after the completion of CRT with additional chemotherapy cycles during the interval period might be a promising option to improve oncological survival in LARC patients treated with CRT and TME without compromising the surgical safety. Further randomized controlled trials investigating this are warranted to prove a clearly causality.

Prognostic value of preoperative neutrophil-to-lymphocyte ratio in histological variants of non-muscle-invasive bladder cancer.

PurposeMany studies identified that the preoperative neutrophil-to-lymphocyte ratio (PNLR) was associated with patient prognosis in non-muscle-invasive bladder cancer (NMIBC). We hypothesized that PNLR could be prognostic in patients with histological variants of NMIBC (VH-NMIBC).Materials and MethodsThis retrospective study included patients with VH-NMIBC admitted at our center between January 2009 and May 2019. The best cut-off value of NLR was measured by the receiver operating characteristic curve and Youden index. The Kaplan-Meier method and Cox proportional hazard regression models were employed to evaluate the association between PNLR and disease prognosis, including recurrence-free survival (RFS), progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS).ResultsA total of 243 patients with VH-NMIBC were enrolled in our study. According to the Kaplan-Meier method results, patients with PNLR ≥2.2 were associated with poor RFS (p<0.001), PFS (p<0.001), CSS (p<0.001), and OS (p<0.001). Multivariable analyses indicated that PNLR ≥ 2.2 was an independent prognostic factor of RFS (hazard ratio [HR], 2.11; 95% confidence interval [CI, 1.57–1.83; p<0.001), PFS (HR, 2.34; 95% CI, 1.70–3.21; p<0.001), CCS (HR, 2.87; 95% CI, 1.96–4.18; p< 0.001), and OS (HR, 2.83; 95% CI, 1.96–4.07; p<0.001).ConclusionsThis study identified that PNLR ≥2.2 was usually associated with a poor prognosis for patients with VH-NMIBC.

Postoperative Complications Predict Long-term Outcome After Curative Resection for Perforated Colorectal Cancer.

Perforation and postoperative complications have a negative effect on long-term outcomes in patients with colorectal cancer (CRC). The aim of this study was to evaluate the clinical factors with special reference to postoperative complications predicting the long-term outcome in those for whom curative resection for perforated CRC was performed. Patients who underwent curative resection for perforated CRC at stage II or III from April 2003 to March 2020 were included. Clinical factors were retrospectively analyzed. Forty-four patients met the selection criteria. The 30-day mortality rate was 4.5% and the complication rate was 47.7%. Excluding 30-day mortality, five-year recurrence-free survival (RFS) and overall survival (OS) were 62.3% and 73.6%, respectively. Multivariate analysis showed that postoperative complications (p=0.005) and pT4 pathological factor (p=0.009) were independent prognostic factors for RFS. Only postoperative complications (p=0.023) were an independent prognostic factor for OS. Postoperative complications were significantly associated with RFS and OS, and pT4 was associated with RFS. The prevention and management of postoperative adverse events may be important for perforated CRC.

Serum solubleB7-H3is a prognostic marker for patients with non-muscle-invasivebladder cancer.

B7-H3 is a member of the B7 family of immune-regulatory ligands and is a costimulatory molecule promoting the T cell response in vitro. We herein investigated the clinical utility of serum soluble B7-H3 (sB7-H3) in patients with non-muscle invasive bladder cancer (NMIBC). We analyzed 555 patients in whom NMIBC was diagnosed at Tokyo Metropolitan Tama Medical Center between 2008 and 2013. We measured the serum sB7-H3 (sB7-H3) level using the enzyme-linked immunosorbent assay (ELISA) and evaluated the utility of sB7-H3 as a prognostic biomarker for NMIBC. We used the Cox proportional hazards regression model to assess recurrence-free survival (RFS) and progression-free survival (PFS) with the sB7-H3 level. We detected high levels of sB7-H3 in the sera of 47% of patients with NMIBC versus only 8% in healthy donors. The increase of sB7-H3 was significantly associated with poor RFS and PFS. Multivariate analysis showed that elevated sB7-H3 was an independent prognostic factor of RFS and PFS. According to the European Organization for Research and Treatment of Cancer (EORTC), in intermediate-low and intermediate-high risk groups, the presence of sB7-H3 significantly determined the rate of recurrence and progression. Our data suggested that evaluating serum sB7-H3 expression is a useful tool for predicting the prognosis of patients with NMIBC.

Prognostic impact of perirenal fat stranding on oncologic outcomes in ureteral urothelial carcinoma.

PurposePerirenal fat stranding (PRFS) is defined as linear areas of soft-tissue attenuation in the perirenal space that can result from ureteral obstruction. We analyzed the prognostic impact of PRFS on outcomes in patients with ureteral urothelial carcinoma (UC).Materials and MethodsOverall, 126 patients evaluated preoperatively by computerized tomography (CT) scan and diagnosed with ureteral UC following nephroureterectomy between January 2001 and May 2018 were included. We analyzed associations between oncologic outcomes and secondary signs such as hydronephrosis and PRFS.ResultsOverall, 68 patients (54.0%) showed PRFS on preoperative CT scans. The patients' mean age was 66.33±9.49 years. A high pT stage (≥T3) was seen in 47 patients (37.3%) and high-grade tumors were seen in 90 patients (71.4%). Lymphovascular invasion (LVI) was seen in 15 patients (11.9%), and 5 (4.0%) were at the pN1 stage. Multivariate Cox analysis showed that cT stage≥3, PRFS, pT stage≥3, tumor grade, LVI, and pN1 stage were independent prognostic factors of recurrence-free survival (RFS) and cancer-specific survival (CSS) (all p<0.05).ConclusionsPRFS was found to be an independent prognostic factor for RFS and CSS. PRFS is easily detectable in preoperative CT imaging and may be useful for improving the prediction of oncologic outcomes of ureteral UC. Therefore, PRFS along with other important preoperative CT findings can help urologists give preoperative advice to patients with ureteral UC before surgical management.

Comparison of anatomic and non-anatomic resections for very early-stage hepatocellular carcinoma: The importance of surgical resection margin width in non-anatomic resection

BackgroundThe superiority of anatomic resection (AR) over non-anatomic resection (NAR) for very early-stage hepatocellular carcinoma (HCC) has remained a topic of debate. Thus, this study aimed to compare the prognosis after AR and NAR for single HCC less than 2 cm in diameter. MethodsConsecutive patients with single HCC of diameter less than 2 cm who underwent curative hepatectomy between 1997 and 2017 were included in this retrospective study. ResultsIn total, 159 patients were included in this study. Of these, 52 patients underwent AR (AR group) and 107 patients underwent NAR (NAR group). No significant differences were noted in recurrence-free survival (RFS) and overall survival (OS) between the AR and NAR groups (P = 0.236 and P = 0.363, respectively). Multivariate analysis revealed that low preoperative platelet count and presence of satellite nodules were independent prognostic factors of RFS and OS. Wide surgical resection margin did not affect RFS (P = 0.692) in the AR group; however, in the NAR group, RFS was found to be higher with surgical resection margin widths ≥1 cm than with surgical resection margin widths <1 cm (P = 0.038). ConclusionsPrognosis was comparable between the NAR and AR groups for very early-stage HCC with well-preserved liver function. For better oncologic outcomes, surgeons should endeavor in keeping the surgical resection margin widths during NAR ≥1 cm.

Frequent Germline and Somatic Single Nucleotide Variants in the Promoter Region of the Ribosomal RNA Gene in Japanese Lung Adenocarcinoma Patients.

Ribosomal RNA (rRNA), the most abundant non-coding RNA species, is a major component of the ribosome. Impaired ribosome biogenesis causes the dysfunction of protein synthesis and diseases called “ribosomopathies,” including genetic disorders with cancer risk. However, the potential role of rRNA gene (rDNA) alterations in cancer is unknown. We investigated germline and somatic single-nucleotide variants (SNVs) in the rDNA promoter region (positions −248 to +100, relative to the transcription start site) in 82 lung adenocarcinomas (LUAC). Twenty-nine tumors (35.4%) carried germline SNVs, and eight tumors (9.8%) harbored somatic SNVs. Interestingly, the presence of germline SNVs between positions +1 and +100 (n = 12; 14.6%) was associated with significantly shorter recurrence-free survival (RFS) and overall survival (OS) by univariate analysis (p < 0.05, respectively), and was an independent prognostic factor for RFS and OS by multivariate analysis. LUAC cell line PC9, carrying rDNA promoter SNV at position +49, showed significantly higher ribosome biogenesis than H1650 cells without SNV. Upon nucleolar stress induced by actinomycin D, PC9 retained significantly higher ribosome biogenesis than H1650. These results highlight the possible functional role of SNVs at specific sites of the rDNA promoter region in ribosome biogenesis, the progression of LUAC, and their potential prognostic value.

Segmentectomy vs Lobectomy for Clinical Stage IA Lung Adenocarcinoma With Spread Through Air Spaces

This study aimed to investigate the prognosis after segmentectomy as compared with lobectomy for small-sized lung adenocarcinoma with spread through air spaces (STAS). This retrospective study included 609 patients who underwent lobectomy or segmentectomy with lymph node dissection for clinical stage IA lung adenocarcinoma between April 2011 and March 2020 at Hiroshima University Hospital. Patient characteristics and prognosis after segmentectomy and lobectomy were investigated. STAS was detected in 293 patients (48.1%). The recurrence-free survival (RFS) rate was significantly worse with STAS-positive adenocarcinoma than with STAS-negative adenocarcinoma both in patients who underwent lobectomy (5-year RFS, 68.2% vs 90.2%; P<.001) and in patients who underwent segmentectomy (5-year RFS, 81.3% vs 93.0%; P= .003). Among thepatients with STAS, there was no significant difference in RFS between patients who underwent lobectomy (5-year RFS, 68.2%) and those who underwent segmentectomy (5-year RFS, 81.3%; P= .225). In a multivariable analysis using propensity score to adjust clinical patient characteristics, segmentectomy was not found to be an independent prognostic factor of RFS (hazard ratio 0.732, P= .326) among patients with STAS. Among the patients with STAS, only 1 patient (1%) with insufficient resection margin (0.5 mm) had local recurrence and 1 patient (1%) with invasive mucinous adenocarcinoma had recurrence in preserved lobe after segmentectomy. Spread through air spaces was a poor prognostic factor in patients with clinical stage IA lung adenocarcinoma. Prognosis after segmentectomy was comparable with that of lobectomy in lung adenocarcinoma with STAS without increasing locoregional recurrence.

184P Development and external validation of a nomogram to predict recurrence-free survival after R0 resection for stage II/III gastric adenocarcinoma: An international multicenter study

The benefit of adjuvant chemotherapy varies widely among patients with stage II/III gastric cancer (GC), and tools predicting outcomes for this patient subset are lacking. We aimed to develop and validate a nomogram to predict recurrence-free survival (RFS) and the benefits of adjuvant chemotherapy after radical resection in patients with stage II/III GC. Data on patients with stage II/III GC who underwent R0 resection from January 2010 to August 2014 at Fujian Medical University Union Hospital (FMUUH) (n=1240; training cohort) were analyzed by Cox regression to identify independent prognostic factors for RFS. A nomogram including these factors was internally and externally validated in FMUUH (n=306) and a US cohort (n=111), respectively. The multivariable analysis identified age, differentiation, tumor size, number of examined lymph nodes, pT stage, pN stage, and adjuvant chemotherapy as associated with RFS. A nomogram including the above 7 factors was significantly more accurate in predicting RFS compared with the 8th AJCC-TNM staging system for patients in the training cohort. The risk of peritoneal metastasis was higher and survival after recurrence was significantly worse among patients calculated by the nomogram to be at high risk than those at low risk. The nomogram’s predictive performance was confirmed in both the internal and external validation cohorts. A novel nomogram is available as a web-based tool and accurately predicts long-term RFS for GC after radical resection. The tool can also be used to determine the benefit of adjuvant chemotherapy by comparing scores with and without this intervention.

Development and External Validation of a Nomogram to Predict Recurrence-Free Survival After R0 Resection for Stage II/III Gastric Cancer: An International Multicenter Study.

Background: The benefit of adjuvant chemotherapy varies widely among patients with stage II/III gastric cancer (GC), and tools predicting outcomes for this patient subset are lacking. We aimed to develop and validate a nomogram to predict recurrence-free survival (RFS) and the benefits of adjuvant chemotherapy after radical resection in patients with stage II/III GC.Methods: Data on patients with stage II/III GC who underwent R0 resection from January 2010 to August 2014 at Fujian Medical University Union Hospital (FMUUH) (n = 1,240; training cohort) were analyzed by Cox regression to identify independent prognostic factors for RFS. A nomogram including these factors was internally and externally validated in FMUUH (n = 306) and a US cohort (n = 111), respectively.Results: The multivariable analysis identified age, differentiation, tumor size, number of examined lymph nodes, pT stage, pN stage, and adjuvant chemotherapy as associated with RFS. A nomogram including the above 7 factors was significantly more accurate in predicting RFS compared with the 8th AJCC-TNM staging system for patients in the training cohort. The risk of peritoneal metastasis was higher and survival after recurrence was significantly worse among patients calculated by the nomogram to be at high risk than those at low risk. The nomogram's predictive performance was confirmed in both the internal and external validation cohorts.Conclusion: A novel nomogram is available as a web-based tool and accurately predicts long-term RFS for GC after radical resection. The tool can also be used to determine the benefit of adjuvant chemotherapy by comparing scores with and without this intervention.

Development and validation of a prognostic model based on the albumin-to-fibrinogen ratio (AFR) and gamma-glutamyl transpeptidase-to-platelet ratio (GPR) in hepatocellular carcinoma patients

BackgroundOur study aimed to formulate a nomogram based on the albumin-to-fibrinogen ratio (AFR) and gamma-glutamyl transpeptidase-to-platelet ratio (GPR) to predict the prognosis of hepatocellular carcinoma (HCC) patients after curative hepatic resection. MethodsA total of 825 HCC patients who underwent curative resection from 2008 to 2015 in West China Hospital of Sichuan University were divided into a training (n = 616) and a validation (n = 209) cohort. The AFR-GPR risk stratification was generated and confirmed by multivariate analysis. Nomograms for recurrence-free survival (RFS) and overall survival (OS) were constructed. The concordance indexes (C-index), calibration, and decision curve analysis (DCA) were used to assess the predictive performance and clinical benefits of the nomograms. ResultsThe AFR-GPR risk stratification was the independent prognostic factor for RFS (p = 0.044) and OS (p = 0.002) in the training cohort and integrated into the construction of nomograms. The C-indexes of RFS and OS in the training and validation cohorts were 0.654 (95%CI: 0.626–0.681)/0.699 (95%CI: 0.654–0.743) and 0.699 (95%CI: 0.668–0.729)/0.736 (95%CI: 0.684–0.787), respectively. Furthermore, the C-indexes of the nomograms were greater than those of other conventional staging systems. ConclusionOur nomograms based on the AFR-GPR risk stratification presented the more reliable, convenient and accurate prognostic predictions for HCC patients.

C-reactive protein : albumin ratio in patients with resectable intrahepatic cholangiocarcinoma.

BackgroundThe C‐reactive protein : albumin ratio (CAR) has been reported as a novel prognostic marker in several cancers. The aim of this study was to investigate the prognostic value of CAR in patients with intrahepatic cholangiocarcinoma (ICC).MethodsThis was a single‐centre retrospective study of patients who underwent surgery for ICC in a university hospital in Japan between 1998 and 2018. CAR, Glasgow Prognostic Score (GPS) and modified GPS (mGPS) were calculated. Their correlation with recurrence‐free survival (RFS) and overall survival (OS) was analysed with Cox proportional hazards models.ResultsSeventy‐two patients were included in the study. Patients were divided into two groups according to the optimal CAR cut‐off value of 0·02. CAR above 0·02 was associated with higher carbohydrate antigen 19‐9 levels (20·5 versus 66·1 units/ml for CAR of 0·02 or less; P = 0·002), larger tumour size (3·2 versus 4·4 cm respectively; P = 0·031) and a higher rate of microvascular invasion (9 of 28 versus 25 of 44; P = 0·041). RFS and OS were shorter in patients with CAR above 0·02: hazard ratio (HR) 4·31 (95 per cent c.i. 2·02 to 10·63) and HR 4·80 (1·85 to 16·40) respectively. In multivariable analysis CAR above 0·02 was an independent prognostic factor of RFS (HR 3·29 (1·33 to 8·12); P < 0·001), but not OS.ConclusionsCAR was associated with prognosis in patients who had hepatic resection for ICC.

Malic Enzyme 1 Indicates Worse Prognosis in Breast Cancer and Promotes Metastasis by Manipulating Reactive Oxygen Species.

PurposeMalic enzyme 1 (ME1) catalyzes malate to pyruvate and thus promotes glycolysis. Its function in breast cancer remains to be fully clarified. The aim of this work was to investigate the prognostic value of ME1 and its possible mechanism in breast cancer.MethodsWe evaluated ME1 expression in 220 early breast cancer patients with tissue microarray-based immunohistochemistry and explored the relationships between ME1 expression and clinicopathological features. Survival analyses were further performed to determine its prognostic value. The public database was used to confirm tissue microarray results. Further, cell proliferation, migration, invasion ability and reactive oxygen species (ROS) were examined in breast cancer cells.ResultsIn breast cancer tissues, high ME1 expression was significantly associated with larger tumor size, higher incidence of lymph node metastasis and higher incidence of lymph-vascular invasion. High ME1 expression significantly correlated with worse recurrence-free survival (RFS), and was an independent prognostic factor for RFS, which was confirmed by mRNA results in the public database. In vitro, upregulation of ME1 by transfecting MCF-7 cells with virus vector remarkably enhanced viability, motility and epithelial–mesenchymal transition (EMT) and decreased ROS levels, whereas knockdown in MDA-MB-468 cells produced totally opposite effects as expected. When pretreated with oxidizing agent, MCF-7 cells overexpressing ME1 lost its motility, whereas MDA-MB-468 cells with knockdown of ME1 restored its motility when pretreated with antioxidant.ConclusionTo our knowledge, these clinical and experiment works first suggested that ME1 may be a novel biomarker and potential therapeutic target for breast cancer metastasis, and its biological effect is mainly controlled by manipulating ROS.

Machine learning-based histological classification that predicts recurrence of peripheral lung squamous cell carcinoma

BackgroundCancer tissue is composed of both a cancer cell component and a stromal component. The aim of this study was to investigate if the component ratio predicts a prognosis for lung squamous cell carcinoma (SqCC) patients by using a machine learning method. MethodsA total of 135 peripheral SqCC cases (tumor size: 3−5 cm) were enrolled in this study. The areas of the cancer cell component, the necrotic component, and the stromal component were accurately measured via a machine learning method. Each case was divided into the following three subtypes: 1) predominant cancer cell, 2) predominant necrosis, and 3) predominant stroma. The study examined if a particular subtype had prognostic significance. ResultsThe number of cases per subtype of predominant cancer cell, predominant necrosis, and predominant stroma was 59, 6, and 70, respectively. Patients with the predominant stroma subtype had a significantly shorter recurrence free survival (RFS) than did those with the predominant cancer cell subtype (5-yr RFS: 42.3 % vs. 84.3 %,p < 0.01). Also, in pathological stage I patients, the 5-year RFS rate for the predominant stroma subtype was significantly shorter (5-yr RFS: 64.3 % vs. 88.4 %, p < 0.01). In the multivariate analysis of p-stage I patients, the predominant stroma subtype was confirmed to be an independent prognostic factor for RFS (p < 0.01). ConclusionUsing machine learning, the study confirmed that the predominant stroma subtype was an independent factor for RFS, suggesting that the ratio of the stromal component correlates with the malignant potential of SqCC.