Prognostic value of SUVmax in breast cancer and comparative analyses of molecular subtypes: A systematic review and meta-analysis

Background:To assess the prognostic capability of the maximum standardized uptake values (SUV_max) measured in the primary tumor and axillary lymph nodes (ALNs) by pretreatment fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography and analyze outcomes according to the molecular breast cancer subtypes.Methods:The databases were systematically searched using keywords for breast cancer, positron emission tomography/computed tomography, and SUV_max; the extracted studies reported at least 1 form of survival data, event-free survival (EFS) and overall survival. Comparative analyses of the pooled hazard ratios (HRs) for EFS and overall survival were performed to assess their correlations with SUV_max. The pooled HR was estimated using random-effects model according to the results of heterogeneity.Results:Thirteen eligible studies comprising 3040 patients with breast cancer were included. The pooled HRs of high SUV_max in the primary tumor and ALN were 3.01 (95% CI 1.83–4.97, P < .00001; I2 = 82%) and 3.72 (95% CI 1.15–12.01; I2 = 92%; P = .03), respectively. Patients with higher SUV_max demonstrated a poorer survival prognosis. Furthermore, comparative analyses according to the molecular subtypes demonstrated that the SUV_max in the primary tumor or ALN can be a predictive parameter in patients with the luminal subtype disease. Subtype analysis results indicated a significant association of the luminal group, with a HR of 2.65 (95% CI 1.31–5.37; I2 = 27%; P = .007).Conclusions:SUV_max from pretreatment is a significant prognostic factor for EFS in patients with breast cancer. Despite several limitations, correlation with molecular subtype (luminal type) was demonstrated. Further large-scale studies are required to investigate the precise prognostic capability of SUV_max.     

The Risk of Neutropenia and Leukopenia in Advanced Non-Small Cell Lung Cancer Patients Treated With Erlotinib: A Prisma-Compliant Systematic Review and Meta-Analysis

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are a critical member of systemic therapy for advanced non-small-cell lung cancer (NSCLC). Erlotinib is the first-generation EGFR-TKIs, the National Comprehensive Cancer Network (NCCN) guidelines recommend it as a first-line agent in patients with sensitizing EGFR mutations. However, the safety of erlotinib plus chemotherapy (CT) or erlotinib alone for advanced NSCLC remains controversial. We carried out a systematic meta-analysis to determine the overall risk of neutropenia and leukopenia associated with erlotinib.PubMed, EMBASE, CBM, CNKI, WanFang database, The Cochrane library, Web of Science, as well as abstracts presented at ASCO conferences and ClinicalTrials.gov were searched to identify relevant studies. RR with 95% CIs for neutropenia and leukopenia were all extracted. The random-effects model was used to calculate pooled RRs and 95% CIs. Power calculation was performed using macro embedded in SAS software after all syntheses were conducted.We identified 12 eligible studies involving 3932 patients. Erlotinib plus CT or alone relative to CT is associated with significantly decreased risks of neutropenia and leukopenia in patients with advanced NSCLC (RR, 0.38; 95% CI, 0.21–0.71; P = 0.00; incidence: 9.9 vs. 35.2%) and (RR, 0.32; 95% CI, 0.11–0.93; P = 0.04; incidence: 3.5 vs. 11.6%), respectively. The subgroup analysis by erlotinb with or without CT showed that erlotinib combine with CT have no significance decrease the relative risks of neutropenia or leukopenia (RR, 0.98; 95% CI, 0.78–1.23; P = 0.87; incidence: 26.2 vs. 30.5%) and (RR, 0.81; 95% CI, 0.34–1.95; P = 0.64; incidence: 6.5 vs. 9.3%), respectively. However, erlotinib alone could decrease incidence of neutropenia (RR, 0.14; 95% CI, 0.07–0.27; P = 0.00; incidence: 3.7 vs. 40.8%) or leukopenia (RR, 0.07; 95% CI, 0.01–0.45; P = 0.01; incidence: 0.8 vs. 15.7%). The power analysis suggests that a power of 61.31% was determined to detect an RR of 0.38 for neutropenia, and 78.03% for an RR of 0.32 for leukopenia.The present meta-analysis suggested that erlotinib could decrease the incidence of neutropenia and leukopenia in patients with advanced NSCLC undergoing erlotinib regardless of whether combined with CT or not. The subgroup analysis revealed that erlotinib combine with CT did not affect the incidence; however, erlotinib alone could significantly decrease the incidence of neutropenia and leukopenia compared with CT alone.     

Pulmonary Toxicities of Gefitinib in Patients With Advanced Non-Small-Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials

Gefitinib is a selective tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) used to treat adults with EGFR mutation-positive non-small-cell lung cancer (NSCLC). Clinical benefits of gefitinib administration in NSCLC patients have been observed in clinical practice, but the extent of the pulmonary toxicity of gefitinib in patients with advanced NSCLC remains unclear.The aim of this systematic review was to evaluate the overall incidence and risk of gefitinib-related pulmonary toxicity in advanced NSCLC patients.Relevant trials were identified from the databases of Pubmed, Embase, Cochrane Library, and the clinicaltrials.gov of the U.S. National Institutes of Health. The outcomes included the overall incidence, odds ratios (ORs), and 95% confidence intervals (CIs). Fixed-effects models were used in the statistical analyses according to the heterogeneity of the included studies.According to the data from the included trials, the overall incidence of high-grade hemoptysis, pneumonia, pneumonitis, and interstitial lung disease (ILD) was 0.49% (95% CI: 0.24%–0.99%), 2.33% (95% CI: 1.47%–3.66%), 2.24% (95% CI: 1.34%–3.72%), and 1.43% (95% CI: 0.98%–2.09%), respectively. The pooled ORs of high-grade hemoptysis, pneumonia, pneumonitis, and ILD were 1.73 (95% CI: 0.46–6.52; P = 0.42), 0.99 (95% CI: 0.66–1.49; P = 0.95), 4.70 (95% CI: 1.48–14.95; P = 0.0087), and 2.64 (95% CI: 1.22–5.69; P = 0.01), respectively.Gefitinib was associated with a significantly increased risk of high-grade/fatal ILD and pneumonitis compared with the controls, whereas the risk of other high-grade pulmonary events (pneumonia and hemoptysis) was not significant. Careful surveillance of gefitinib-related pulmonary toxicity is critical for the safe use of this drug.     

Semi-Quantitative Calculations of Primary Tumor Metabolic Activity Using F-18 FDG PET/CT as a Predictor of Survival in 92 Patients With High-Grade Bone or Soft Tissue Sarcoma

To assess the prognostic value of primary tumor metabolic activity in patients with high-grade bone sarcomas (BS) or soft tissue sarcomas (STS) using F-18 FDG PET/CT.A single-site, retrospective study including 92 patients with high-grade BS or STS. Pretreatment F-18 FDG PET/CT scan was performed. Clinical data were registered. Accuracy of maximum standardized uptake value of primary tumor (SUV_max) and tumor-to-background (T/B) uptake ratio as prognostic variables and identification of cut-off values to group patients were determined. Kaplan–Meier survival estimates and log-rank test were used to compare survival distributions. Prognostic variables were assessed using Cox proportional hazards regression analysis.Forty-one of 92 patients died during follow-up (45%). Average survival was 6.5 years (95% CI 5.8–7.3 years) and probability of 5-year survival was 52%. Accuracy of SUV_max and T/B uptake ratio as prognostic variables in all patients and during subgroup analysis of patients with STS was significant. No significant results for AUCs were registered in patients with BS. Surgery was independently prognostic for survival throughout multivariate regression analysis of all patients (P = 0.001, HR 3.84) and subgroup analysis (BS: P = 0.02, HR 11.62; STS: P = 0.005, HR 4.13). SUV_max was significant as prognostic variable in all patients (P = 0.02, HR 3.66) and in patients with STS (P = 0.007, HR 3.75). No significant results were demonstrated for T/B uptake ratio.Estimation of primary tumor metabolic activity with pretherapeutic SUV_max using F-18 FDG PET/CT demonstrates independent properties beyond histologic grading for prediction of survival in patients with high-grade STS, but not with high-grade BS.     

Relationship Between 18F-Fluorodeoxyglucose Uptake and V-Ki-Ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog Mutation in Colorectal Cancer Patients: Variability Depending on C-Reactive Protein Level

To evaluate clinical values of clinicopathologic and ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT)-related parameters for prediction of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation in colorectal cancer (CRC) and to investigate their variability depending on C-reactive protein (CRP) levels.In total, 179 CRC patients who underwent PET/CT scans before curative resection and KRAS mutation evaluation following surgery were enrolled. Maximum standardized uptake value (SUV_max), peak standardized uptake value (SUV_peak), metabolic tumor volume, and total lesion glycolysis were determined semiquantitatively. Associations between clinicopathologic and PET/CT-related parameters and KRAS expression were analyzed.Elevated CRP (>6.0 mg/L; n = 47) was associated with higher primary tumor size, higher SUV_max, SUV_peak, metabolic tumor volume, and total lesion glycolysis, compared with those for the group with a CRP lower than that the cutoff value (<6.0 mg/L; n = 132). Interestingly, the CRC patients (having CRP < 6.0 mg/L) with KRAS mutations had significantly higher (P < 0.05) SUV_max and SUV_peak values than the patients expressing wild-type KRAS mutations. Multivariate analysis revealed SUV_max and SUV_peak to be significantly associated with KRAS mutations (odds ratio = 3.3, P = 0.005, and odds ratio = 3.9, P = 0.004), together with histologic grade and lymph node metastasis.¹⁸F-FDG uptake was significantly higher in CRC patients with KRAS mutations and with normal CRP levels. A severe local inflammation with raised CRP levels, however, might affect accurate ¹⁸F-FDG quantification in CRC tumors. Positron emission tomography/computed tomography-related parameters could supplement genomic analysis to determine KRAS expression in CRC; however, care should be exercised to guarantee proper patient selection.     

Clinicopathological significance and prognostic value of E-cadherin expression in non-small cell lung cancer: A protocol for systematic review and meta-analysis

Background:E-cadherin, a calcium-dependent cell adhesion molecule, as an important mediator of adhesion and signaling pathway, plays a key role in maintaining tissue integrity. However, the association of E-cadherin expression with clinicopathological features and prognostic value in non-small cell lung cancer (NSCLC) is still controversial. Therefore, the purpose of the study is to explore the clinicopathological features and prognostic value of E-cadherin expression in non-small cell lung cancer by meta-analysis.Methods:PubMed, EMBASE, Cochrane Library, and Web of Science were searched to collect the studies about expression of E-cadherin and clinicopathological features and prognosis of non-small cell lung cancer. The last search time was May 2020. Stata 15.0 software was used for statistical analysis.Results:A total of 35 studies were included, of which the results showed that high expression of E-cadherin compared with its low expression, for overall survival, HR = 0.68 (95% CI:0.64–0.73, P < .05); for disease-free survival or progression-free survival, HR = 0.54 (95% CI: 0.44–0.67); low differentiation of lung cancer compared with moderate and high differentiation, OR = 0.40 (95% CI: 0.27–0.58, P < .05); Advanced lung cancer compared with early stage, OR = 0.54 (95% CI: 0.44–0.66, P < .05); lymph node metastasis compared with non-lymph node metastasis, OR = 0.49 (95% CI: 0.31∼0.77).Conclusion:Low expression of E-cadherin is closely related to poor prognosis of patients with NSCLC, promoting tumor staging and lymph node metastasis, inhibiting tumor differentiation as well.     

Simple prognostic markers for optimal treatment of patients with unresectable pancreatic cancer

Most patients with pancreatic cancer are ineligible for curative resection at diagnosis, resulting in poor prognosis. This study aimed to evaluate the prognostic factors in patients with unresectable pancreatic cancer.We retrospectively collected clinical data from 196 patients with unresectable pancreatic cancer who received palliative chemotherapy (N = 153) or palliative care alone (N = 43) from January 2011 to December 2013. Patients’ background data and overall survival were analyzed using the Cox proportional hazard regression model.In patients receiving palliative chemotherapy (gemcitabine-based regimen, 88.2%) and palliative care alone, the median (range) ages were 68 (43–91) and 78 (53–90) years, and metastatic diseases were present in 80% (N = 123) and 86% (N = 37), respectively. Multivariate analysis in the palliative chemotherapy patients showed that liver metastasis (hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.58–3.20, P < .001), neutrophil-to-lymphocyte ratio (>4.5 vs ≤4.5; HR 3.45, 95% CI 2.22–5.36, P < .001), and cancer antigen 19-9 (CA19-9) (≥900 vs <900 U/mL; HR 1.45, 95% CI 1.02–2.05, P = .036) were independent prognostic factors. In those receiving palliative care alone, lung (HR 3.27, 95% Cl 1.46-7.35, p = 0.004) and peritoneum (HR 2.50, 95% CI 1.20–5.18, P = .014) metastases and the C-reactive protein-to-albumin ratio (≥1.3 vs <1.3; HR 3.33, 95% Cl 1.51–7.35, P = .003) were independent prognostic factors. Furthermore, patients with multiple factors had worse prognosis in both groups. Median survival time of palliative chemotherapy patients with risk factors 0, 1, 2, and 3 were 13.1 (95% CI 8.0–16.9), 9.4 (95% CI 7.9–10.1), 6.6 (95% CI 4.9–7.8), and 2.5 (95% CI 1.7–4.0) months, respectively. Similarly, median survival time was 5.7 (95% CI 1.3 -8.0), 2.1 (95% CI 1.5–3.9), and 1.3 (95% CI 0.6–1.7) months, respectively, for palliative care alone patients with risk factor 0, 1, and 2 to 3.Prognostic markers for pancreatic cancer were neutrophil-to-lymphocyte ratio, liver metastasis, and CA19-9 in patients undergoing palliative chemotherapy and C-reactive protein-to-albumin ratio and lung/peritoneum metastases in patients undergoing palliative care alone. These simple markers should be considered when explaining the prognosis and therapeutic options to patients.     

Clinicopathologic Significance and Prognostic Value of B7 Homolog 1 in Gastric Cancer: A Systematic Review and Meta-Analysis

Immunologic checkpoint marker B7 homolog 1 (B7-H1) plays a fundamental role in the initiation and progression of gastric cancer (GC); however, the clinicopathologic significance and prognostic value of B7-H1 in GC remains controversial. In this study, we aimed to assess their relationship through a meta-analysis.Medline/PubMed, EMBASE, the Cochrane Library databases, and Grey literature were searched up to August 10, 2015, for eligible studies of the association between B7-H1 expression and overall survival in GC. The hazard ratio and its 95% confidence interval (CI) were calculated from the included studies. Moreover, the odds ratio (OR) was also extracted to evaluate the association between the clinicopathologic parameters of participants and B7-H1 expression.Five studies involving 481 patients were included in the meta-analysis. The pooled results showed that positive B7-H1 expression was a negative predictor for overall survival with hazard ratio of 1.74 (95% CI: 1.40–2.17; P_{heterogeneity} = 0.146) in GC. Additionally, increased B7-H1 was found to be significantly associated with positive lymph node metastasis (OR = 2.61, 95% CI: 1.78–3.84; P_{heterogeneity} = 0.004) and poorer tumor stage (OR = 2.28, 95% CI: 1.39–3.74; P_{heterogeneity} = 0.006); however, higher B7-H1 expression was not significantly correlated with poorer tumor differentiation (OR = 1.29, 95% CI: 0.90–1.86; P_{heterogeneity} = 0.013) and bigger tumor size (OR = 1.18, 95% CI: 0.81–1.73; P_{heterogeneity} = 0.104).The meta-analysis suggested that B7-H1 could act as a significant biomarker in the poor prognosis of gastric carcinoma.     

Risk factors for postoperative pneumonia and prognosis in lung cancer patients after surgery: A retrospective study

Postoperative pneumonia (POP) is one of the most frequent complications following lung surgery. The aim of this study was to identify the risk factors for developing POP and the prognostic factors in lung cancer patients after lung resection.We performed a retrospective review of 726 patients who underwent surgery for stages I–III lung cancer at a single institution between August 2017 and July 2018 by conducting logistic regression analysis of the risk factors for POP. The Cox risk model was used to analyze the factors influencing the survival of patients with lung cancer.We identified 112 patients with POP. Important risk factors for POP included smoking (odds ratio [OR], 2.672; 95% confidence interval [CI], 1.586–4.503; P < .001), diffusing capacity for carbon monoxide (DLCO) (40–59 vs ≥80%, 4.328; 95% CI, 1.976–9.481; P < .001, <40 vs ≥80%, 4.725; 95% CI, 1.352–16.514; P = .015), and the acute physiology and chronic health evaluation (APACHE) II score (OR, 2.304; 95% CI, 1.382–3.842; P = .001). In the Cox risk model, we observed that age (hazard ratios (HR), 1.633; 95% CI, 1.062–2.513; P = .026), smoking (HR, 1.670; 95% CI, 1.027–2.716; P = .039), POP (HR, 1.637; 95% CI, 1.030–2.600; P = .037), etc were predictor variables for patient survival among the factors examined in this study.The risk factors for POP and the predictive factors affecting overall survival (OS) should be taken into account for effective management of patients with lung cancer undergoing surgery.     

Clinicopathological and prognostic significance of NM23 expression in patients with non-small cell lung cancer: A systematic review and meta-analysis

Background:There is a heated debate on the clinicopathological features and prognostic significance with non-metastasis 23 (NM23) expression in patients with non-small cell lung cancer (NSCLC). Thus, we conducted this meta-analysis to evaluate the clinicopathological features and prognostic significance of NM23 for NSCLC patients.Methods:Pubmed, Embase, and Web of Science were exhaustively searched to identify relevant studies published prior to March, 2020. Odds radios (ORs) and hazard radios with 95% confidence intervals (CIs) were calculated to summarize the statistics of clinicopathological and prognostic assessments. Q-test and I²-statistic were utilized to assess heterogeneity across the included studies. We also performed subgroup analyses and meta-regression analyses to identify the source of heterogeneity. Publication bias was detected by Begg and Egger tests. Sensitivity analysis was used to value the stability of our results. All the data were analyzed using statistical packages implemented in R version 4.0.5.Results:Data from a total of 3170 patients from 36 studies were extracted. The meta-analysis revealed that low expression of NM23 was correlated with higher risk of NSCLC (OR = 4.35; 95% CI: 2.76–6.85; P < .01), poorer tumor node metastasis (TNM) staging (OR = 1.39; 95% CI: 1.01–1.90; P = .04), poorer differentiation degree (OR = 1.37; 95% CI: 1.01–1.86; P = .04), positive lymph node metastasis (OR = 1.83; 95% CI: 1.22–2.74; P < .01), lung adenocarcinoma (OR = 1.45; 95% CI: 1.20–1.75; P < .01), and poorer 5-year overall survival (OS) rate (hazard radio = 2.33; 95%CI: 1.32–4.11; P < .01). The subgroup analyses and meta-regression analyses suggested that the “Publication year”, “Country”, “Sample size”, and “Cutoff value” might be the source of heterogeneity in TNM staging, differentiation degree, and lymph node metastasis. Both Begg test and Egger test verified that there were publication bias in 5-year OS rate. Sensitivity analysis supported the credibility of the results.Conclusion:The reduced NM23 expression is strongly associated with higher risk of NSCLC, higher TNM staging, poorer differentiation degree, positive lymph node metastasis, lung adenocarcinoma, and poorer 5-year OS rate in NSCLC patients, which indicated that NM23 could serve as a biomarker predicating the clinicopathological and prognostic significance of NSCLC.     

Extent of Serosal Changes Predicts Peritoneal Recurrence and Poor Prognosis After Curative Surgery for Gastric Cancer

To investigate whether the width of gastric serosal lesions in advanced gastric cancer patients have a predictive value for peritoneal recurrence and the 5-year survival rate.A total of 1109 patients with advanced noncardia primary gastric adenocarcinoma, who underwent curative gastrectomy between January 1997 and December 2007, were included. Data about tumor size, longitudinal tumor location, resection type, serum albumin concentration, lymphatic/venous invasion, lymph node metastasis status, lesion size, histological and Borrmann type of tumor, as well as the recurrence rate and width of the gastric serosal lesions were collected and analyzed.The peritoneal recurrence rate in patients with gastric serosal lesions ≤3 cm was lower than in patients with gastric serosal lesions >3 cm. Multivariate analyses of the 5-year survival rate variables for all patients revealed significant correlations with serum albumin concentrations (HR 1.382, P = 0.002, 95% CI 1.123–1.701), width of serosa changes (HR 1.377, P = 0.020, 95% CI 1.053–1.802), depth of invasion (HR 1.529, P < 0.001, 95% CI 1.288–1.814), and lymph node metastasis (HR 1.551, P < 0.001, 95% CI 1.420–1.694), whereas for recurrent patients only serum albumin concentrations (HR 2.000, P < 0.001, 95% CI 1.425–2.805), width of serosa changes (HR 1.867, P = 0.002, 95% CI 1.248–2.793), and lymph node metastasis (HR 1.521, P < 0.001, 95% CI 1.249–1.852) correlated with the 5-year survival rate.Gastric serosal lesions >3 cm may indicate a high risk for peritoneal recurrence and serve as additional indicators for preventive postoperative adjuvant chemotherapies in patients with advanced gastric cancer.     

Short-term Follow-up US Leads to Higher False-positive Results Without Detection of Structural Recurrences in PTMC

To investigate the value of the annual follow-up neck ultrasonography (US) for postoperative surveillance in patients with papillary thyroid microcarcinoma (PTMC).This retrospective study has been approved by our institutional review board (IRB) with waiver for informed consent. A total of 375 patients diagnosed as PTMCs, who underwent total thyroidectomy with radioiodine remnant ablation were included, to identify the recurrence rate and the false-positive rate of annual ultrasound. The number, interval, and the results of follow-up US or fine needle aspiration were obtained from electronic medical records.Four (1.1%, 4/375) recurrences were found 3 years after the initial treatment, and only 1 patient (0.3%, 1/375) had a metastatic lymph node larger than 8 mm in the shortest diameter on US found 7.6 years after initial treatment with biochemical abnormalities. Cumulative risk of having at least 1 false-positive exam was 8.3% by the 8th US, and 8.1% by the 8–9 year follow-up. Cox multivariate regression showed shorter interval of follow-up US and presence of lymph node metastasis at initial surgery are independent predictors affecting the cumulative false-positive results (hazard ratio [HR], 0.60; 95% confidence interval [CI]: 0.49–0.73; P < 0.001 and HR, 2.19; 95% CI: 1.01–4.75; P = 0.048, respectively).Short-term follow-up US can result in higher cumulative false-positive results without detection of meaningful recurrences in patients with PTMCs who do not have biochemical abnormalities.     

Prognostic Value of the Sum of Metabolic Tumor Volume of Primary Tumor and Lymph Nodes Using 18F-FDG PET/CT in Patients With Cervical Cancer

This is an observational study to determine the most relevant parameter of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for predicting recurrence in cervical cancer.Fifty-six patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIB-IVA cervical cancer who underwent pretreatment ¹⁸F-FDG PET/CT were enrolled. PET parameters including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of both primary tumor and pelvic and/or para-aortic lymph nodes were analyzed. SUVmax-S was defined as the sum of the SUVmax of primary tumor and the higher SUVmax of either pelvic or para-aortic lymph nodes. MTV-S was defined as the sum of the MTV of primary tumor and pelvic and para-aortic lymph nodes. TLG-S was calculated in the same way as MTV-S. We evaluated the relationship between these PET parameters and recurrence-free survival (RFS).Univariate analysis revealed that higher FIGO stage (hazard ratio [HR] = 5.61, 95% confidence interval [CI]: 1.68–18.68, P = 0.005), lymph node metastasis (HR = 3.42, 95% CI: 1.08–10.84, P = 0.037), MTV of primary tumor >47.81 cm³ (HR = 6.20, 95% CI: 1.35–28.48, P = 0.019), TLG of primary tumor >215.02 (HR = 11.82, 95% CI: 1.52–91.96, P = 0.018), MTV-S > 59.01 cm³ (HR = 8.24, 95% CI: 1.80–37.77, P = 0.007), and TLG-S > 224.15 (HR =  13.09, 95% CI: 1.68–101.89, P = 0.014) were associated with RFS. In multivariate analysis, FIGO stage (HR = 4.87, 95% CI: 1.38–17.18, P = 0.014) and MTV-S > 59.01 cm³ (HR = 7.37, 95% CI: 1.54–35.16, P = 0.012) were determined to be independent predictive factors for RFS.Our preliminary results reveal that MTV-S is an independent prognostic factor for RFS in patients with cervical cancer treated by definitive chemoradiotherapy.     

Low Discrepancy Between Tissue Biopsy Plus Magnifying Endoscopy With Narrow-Band Imaging and Endoscopic Resection in the Diagnosis of Gastric Epithelial Neoplasia (STROBE)

Tissue biopsy is often not very accurate for the diagnosis of gastric epithelial neoplasia (GEN), and the results differ notably from endoscopic resection (ER) in terms of the pathological diagnosis. The aims of this study were to evaluate the diagnostic performances of biopsy, magnifying endoscopy with narrow-band imaging (ME-NBI), and biopsy plus ME-NBI for GEN.This study retrospectively analyzed 101 cases diagnosed as GEN using ER samples. The discrepancies between biopsy and ER, as well as between biopsy plus ME-NBI and ER in the diagnosis of GEN were evaluated. Factors that contributed to such discrepancies were analyzed. The sensitivity and specificity of biopsy and ME-NBI for the diagnosis of high-grade neoplasia (HGN) were determined.The discrepancy in the pathological diagnosis between biopsy and ER was 39.6% for GEN and 54.2% for HGN. The discrepancy between biopsy combined with ME-NBI and ER was 15.9% for GEN and 10.2% for HGN. Factors that undermined the diagnostic accuracy of biopsy included the lesion size (≤10 mm, odds ratio [OR] 1; 10–20 mm, OR 0.2, 95% confidence interval [CI] 0.1–0.7; >20 mm, OR 0.5, 95% CI 0.1–2.1, P = 0.03) and the number of biopsy fragments (OR 0.6, 95% CI 0.5–0.8, P = 0.001). The sensitivity and specificity for HGN were 45.8% (33.7%–58.3%) and 100% (87.5%–100%) for biopsy, and 88.1% (77.5%–94.1%) and 92.9% (81.0%–97.5%) for ME-NBI, respectively.In conclusion, biopsy-based diagnoses for GEN should be interpreted with caution. Biopsy combined with ME-NBI can contribute to the diagnosis of GEN, which improves diagnostic consistency with pathological result of ER specimens.     

The predictive and prognostic effects of PD-L1 expression on TKI treatment and survival of EGFR-mutant NSCLC: A meta-analysis

Whether programmed death-ligand 1 (PD-L1) expression could predict the outcome of tyrosine kinase inhibitor (TKI) treatment and prognosis of epidermal growth factor receptor (EGFR)-mutant nonsmall cell lung cancer (NSCLC) is remaining controversial.Potential studies were search from PubMed, Embase, and Web of Science databases. Pooled odds ratio of objective response rate was used to describe the relationship between PD-L1 expression and primary resistance to EGFR-TKIs. Pooled hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS) were included to assess the effects of PD-L1 status on the outcome of EGFR-TKI treatment and survival of EGFR-mutant NSCLCs.Eighteen eligible studies (1986 EGFR-mutant NSCLCs) were included in this meta-analysis. Positive PD-L1 expression correlated with lower objective response rate of EGFR-TKI treatment (odds ratio [95% confidence interval {CI}] = 0.52 [0.28–0.98], P = .043), while PFS (adjusted HR [95% CI] = 1.49 [0.96–1.89], P = .332) and OS (HR [95% CI] = 1.24 [0.70–2.20], P = .456) of EGFR-TKI treatment did not correlated with PD-L1 status. Furthermore, PD-L1 expression was not a predictive biomarker for the OS (HR [95% CI] = 1.43 [0.98–2.08], P = .062) in overall EGFR-mutant cohort.Positive PD-L1 expression indicated a higher incidence of primary resistance, but did not correlate with the PFS or OS of EGFR-TKI therapy. In addition, PD-L1 expression was unlikely a predictive biomarker for prognosis of EGFR-mutant NSCLCs.     

The Efficacy of Combining EGFR Monoclonal Antibody With Chemotherapy for Patients With Advanced Nonsmall Cell Lung Cancer: A Meta-Analysis From 9 Randomized Controlled Trials

Although epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) have been proved synergistic effect when combined with cytotoxic agents for advanced nonsmall cell lung cancer (NSCLC), the results of relevant clinical trials remain controversial. The purpose of this meta-analysis was to assess the advantage and toxicity profile of chemotherapy plus EGFR-mAbs versus chemotherapy alone for patients with NSCLC.We rigorously searched electronic databases for eligible studies reporting EGFR-mAbs combined with chemotherapy versus chemotherapy alone for patients with advanced NSCLC. The primary outcome was overall survival (OS). Pooled results were calculated using proper statistical methods.Nine phase II/III randomized controlled trials involved a total of 4949 participants were included. In general, compared with chemotherapy alone, the addition of EGFR-mAbs significantly improved OS (hazard ratio [HR] = 0.91, 95% confidence interval [CI]: 0.86–0.97, P = 0.006), progression-free survival (HR = 0.83, 95% CI: 0.87–0.98, P = 0.01), response rate (odd ratio [OR] = 1.28, 95% CI: 1.12–1.47, P = 0.0003), and disease control rate (OR = 1.17, 95% CI: 1.01–1.36, P = 0.04). Subgroup analysis showed that apparent OS benefit present in patients with squamous NSCLC (HR = 0.83, 95% CI: 0.74–0.93, P = 0.001), and those treatment-naive population (HR = 0.88, 95% CI: 0.82–0.95, P = 0.0006). Several manageable adverse events were markedly increased by EGFR-mAbs, such as acne-like rash, infusion reactions, and diarrhea. The risk for some ≥Grade 3 toxicities, such as leukopenia, febrile neutropenia, and thromboembolic events were slightly increased by the addition of EGFR-mAbs. In general, the toxicities of the combination strategy were tolerable and manageable.The addition of EGFR-mAbs to chemotherapy provided superior clinical benefit along with acceptable toxicities to patients with advanced NSCLC, especially those harboring squamous cancer and treatment-naive. Further validation in front-line investigation, proper selection of the potential benefit population by tumor histology, and development of prognostic biomarkers are warranted for future research and clinical application of EGFR-mAbs.     

The relationship between hepatoma-derived growth factor and prognosis in non-small cell lung cancer: A systematic review and meta-analysis

Background:Hepatoma-derived growth factor (HDGF) promotes cancer progression and metastasis by interacting with vascular endothelial growth factor, thereby inducing epithelial-to-mesenchymal transition and angiogenesis. Recent studies have correlated increased HDGF levels with poor prognosis in various malignancies, including lung cancer. This meta-analysis systematically assessed the prognostic significance of HDGF expression in patients with non-small cell lung cancer (NSCLC).Methods:Eligible studies were identified by searching literature in PubMed, Embase, Scopus, and the Cochrane library until June 2020. The pooled hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) was determined to assess the relationship between HDGF expression and clinical outcome in patients with NSCLC.Results:The pooled HRs between high HDGF expression and clinical outcome were 2.20 (95% CI 1.75–2.76, P < .001) and 2.77 (95% CI 1.79–4.29, P < .001) for overall survival and disease-free survival, respectively. High HDGF expression was significantly correlated with a larger tumor size (OR 1.59, 95% CI 1.02–2.46, P = .040).Conclusion:HDGF expression is related to clinical outcome and may be a prognostic marker in patients with NSCLC.     

Volume-Based F-18 FDG PET/CT Imaging Markers Provide Supplemental Prognostic Information to Histologic Grading in Patients With High-Grade Bone or Soft Tissue Sarcoma

The aim of the study is to assess the prognostic value of different volume-based calculations of tumor metabolic activity in the initial assessment of patients with high-grade bone sarcomas (BS) and soft tissue sarcomas (STS) using F-18 FDG PET/CT.A single-site, retrospective study from 2002 to 2012 including 92 patients with histologically verified high-grade BS (N = 37) or STS (N = 55). All patients underwent a pretreatment F-18 FDG PET/CT scan. Clinical data were registered. Measurements of the accuracy of metabolic tumor volume with a preset threshold of 40% of the maximum standardized uptake value of primary tumor (MTV_40%) and total lesion glycolysis (TLG) as prognostic variables and identification of optimal discriminating cut-off values were performed through ROC curve analysis. Patients were grouped according to the cut-off values. All deaths were considered an event in survival analysis. Kaplan–Meier survival estimates and log-rank test were used to compare the degree of equality of survival distributions. Prognostic variables with related hazard ratios (HR) were assessed using Cox proportional hazards regression analysis.Forty-one of 92 patients died during follow-up (45%; 12 BS and 29 STS). Average survival for included patients was 6.5 years (95% CI 5.8–7.3 years) and probability of 5-year survival was 52%. There was a high-significant accuracy of TLG and MTV_40% as prognostic variables when looking on all patients and during subgroup analysis. AUCs were higher for TLG than for MTV_40%. TLG above optimal cut-off value was the only variable which was independently prognostic for survival throughout multivariate regression analysis of all included patients (P = 0.01, HR 4.78 [95% CI 1.45–15.87]) and subgroup analysis (BS: P = 0.04, HR 11.11 [95% CI 1.09–111.11]; STS: P < 0.05, HR 3.37 [95% CI 1.02–11.11]). No significant results were demonstrated for MTV_40%.Volume-based F-18 FDG PET/CT imaging markers in terms of pretreatment estimation of TLG provide supplemental prognostic information to histologic grading, with significant independent properties for prediction of overall survival in patients with high-grade BS or STS.     

The Highest Metabolic Activity on FDG PET Is Associated With Overall Survival in Limited-Stage Small-Cell Lung Cancer

We evaluated the prognostic value of ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG PET) parameters for limited-stage small-cell lung cancer (LS-SCLC).We retrospectively enrolled 59 LS-SCLC patients who underwent pretreatment FDG PET/CT. Various PET parameters were measured in all malignant lesions, and we recorded the highest maximum standardized uptake value (SUV_max), and sum of metabolic tumor volume (MTV_sum) and total lesion glycolysis (TLG_sum). The relationship between the highest SUV_max and volumetric PET parameters was evaluated. The prognostic significances of PET parameters and clinical variables were assessed using Cox''s proportional hazard regression analysis. Overall survival (OS) and progression-free survival (PFS) were assessed by the Kaplan–Meier method.The SUV_max of the highest metabolic lesion had a significant positive correlation with MTV_sum and TLG_sum (P < 0.001). Upon multivariate analysis, the highest SUV_max was an independent predictor of OS (1 unit increase, hazard ratio [HR]: 1.133, P = 0.003) and MTV_sum was a significant prognostic factor of PFS (10-cm³ increase, HR: 1.027, P = 0.034) after adjusting for age, sex, performance status, tumor stage, and treatment modality. The highest SUV_max was a prognostic factor for PFS with marginal significance (1 unit increase, HR: 1.078, P = 0.053). Patients with higher SUV_max (≥11) were also characterized by a significantly shorter median OS (P < 0.001) and PFS (P = 0.002) compared with patients with lower SUV_max.The highest SUV_max is an independent prognostic factor for survival in LS-SCLC patients. Therefore, the highest SUV_max might be a possible imaging biomarker for risk stratification in LS-SCLC. A further study in a large cohort is needed to validate the prognostic significance of the parameter.     

Association between Alpha B-crystallin expression and prognosis in patients with solid tumors: A protocol for systematic review and meta-analysis

Background:Alpha B-crystallin (CRYAB), as a small heat shock protein, may play critical roles in the tumorigenesis and progression of several kinds of human cancers. However, the prognostic value of CRYAB in solid malignancies remains controversial. The aim of the present study was to investigate the association between CRYAB expression and clinicopathology and prognosis of solid tumor patients.Methods:PubMed, Web of Science, EMBASE, Chinese National Knowledge Infrastructure, and WanFang databases were systematically searched to retrieve studies that investigated the prognostic value of CRYAB expression in various solid tumors. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to determine the strength of association between CRYAB expression and survival in patients with solid tumors. Odds ratios (ORs) with 95% CIs were pooled to assess the correlation between CRYAB expression and clinicopathological characteristics of patients with solid tumors.Results:A total of 17 studies, including 18 cohorts with 6000 patients, were included in this meta-analysis. Our results showed that increased CRYAB expression could predict poor overall survival (HR = 1.81, 95% CI: 1.50–2.19, P < .001), disease-free survival (HR = 1.47, 95% CI: 1.16–1.86, P = .001), and disease-specific survival (HR = 1.40, 95% CI: 1.19–1.63, P < .001) in patients with cancer. Furthermore, the high expression level of CRYAB was associated with certain phenotypes of tumor aggressiveness, such as lymph node metastasis (OR = 2.46, 95% CI: 1.48–4.11, P = .001), distant metastasis (OR = 3.34, 95% CI: 1.96–5.70, P < .001), advanced clinical stage (OR = 2.24, 95% CI: 1.24–4.08, P = .008), low OS rate (OR = 4.81, 95% CI: 2.82–8.19, P < .001), and high recurrence rate (OR = 1.38, 95% CI: 1.11–1.72, P = .004).Conclusions:CRYAB may serve as a valuable prognostic biomarker and therapeutic target in human solid tumors.