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.     

Predictive value of metabolic activity detected by pre-operative 18F FDG PET/CT in ampullary adenocarcinoma

In ampullary adenocarcinoma cases, the clinical effects of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) have not yet been well-studied, unlike other prognostic factors that have been reported till date. This study aimed to investigate the clinical impact of maximum standardized uptake value (SUVmax) in predicting the prognosis of ampullary adenocarcinoma.Thirty-eight patients who underwent pre-operative ¹⁸F-FDG PET/CT and curative-intent resection of ampullary adenocarcinoma at Pusan National University Hospital (Pusan, South Korea) between 2008 and 2017 were retrospectively analyzed in this study. We evaluated the clinicopathologic outcomes according to the SUVmax using univariate and multivariate Cox proportional hazard regression analyses and receiver operating characteristic analysis to arrive at a cutoff value.Lymph node metastasis was detected in 9 patients, and 15 patients experienced a recurrence during the follow-up period. Among 38 patients, 33 showed an increased FDG uptake by the main tumor. SUVmax of 4.55 was selected as a significant independent predictive factor for patient survival along with poor tumor differentiation and high neutrophil-to-lymphocyte ratio in multivariate analysis (P = .016, hazard ratio = 5.040). Patients with SUVmax under 4.55 exhibited significantly longer overall survival than the rest (<4.55 vs ≥4.55), and the 5-year overall survival was 82.8% versus 57.4% (P = .049).SUVmax of 4.55 on ¹⁸F-FDG PET/CT could be a predictive factor for tumor biology and long-term survival in patients with ampullary adenocarcinoma. Nevertheless, considering the cost aspect and its limited prognostic effect, this study seems to require more patient and multicenter studies.     

Positron Emission Tomography With 18F-Fluorodeoxyglucose in Patients With Sickle Cell Acute Chest Syndrome

The acute chest syndrome (ACS) is the main cause of mortality among adult patients with sickle cell disease (SCD). Its pathophysiology is still unclear. Using positron emission tomography (PET) with ¹⁸F-fluorodeoxyglucose [18F-fluorodeoxyglucose (¹⁸F-FDG)], we explored the relationship between regional lung density and lung metabolism, as a reflection of lung neutrophilic infiltration during ACS.Patients were prospectively enrolled in a single-center study. Dual modality chest PET/computed tomography (CT) scans were performed, with ¹⁸F-FDG emission scans for quantification of regional ¹⁸F-FDG uptake and CT scans with radiocontrast agent to check for pulmonary artery thrombosis. Regional lung ¹⁸F-FDG uptake was quantified in ACS patients and in SCD patients without ACS (SCD non-ACS controls). Maximal (SUVmax) and mean (SUVmean) standardized uptake values were computed.Seventeen patients with ACS (mean age 28.3 ± 6.4 years) were included. None died nor required invasive mechanical ventilation. The main lung opacity on CT scans was lower lobe consolidation. Lungs of patients with ACS exhibited higher SUVmax than those of SCD non-ACS controls (2.5 [2.1–2.9] vs 0.8 [0.6–1.0]; P < 0.0001). Regional SUVmax and SUVmean was higher in lower than in upper lobes of ACS patients (P < 0.001) with a significant correlation between lung density and SUVmax (R² = 0.78). SUVmean was higher in upper lobes of ACS patients than in lungs of SCD non-ACS controls (P < 0.001). Patients with SUVmax >2.5 had longer intensive care unit (ICU) stay than others (7 [6–11] vs 4 [3–6] days; P = 0.016).Lungs of patients with ACS exhibited higher ¹⁸F-FDG uptake than SCD non-ACS controls. Lung apices had normal aeration and lower ¹⁸F-FDG uptake than lung bases, but higher ¹⁸F-FDG uptake than lungs of SCD non-ACS controls. Patients with higher lung ¹⁸F-FDG uptake had longer ICU stay than others.     

Clinical significance of prognostic nutritional index in renal cell carcinomas

Prognostic nutritional index (PNI) could reflect the nutrition and inflammation status in cancer patients. This study aims to identify the prognostic significance of PNI in patients with renal cell carcinoma (RCC).A total of 694 RCC patients from our institution were included in this study. The prognostic correlation between PNI and overall survival (OS) and recurrence-free survival (RFS) was analyzed respectively using Kaplan–Meier method and univariate and multivariate Cox model. Studies about the association between pretreatment or preoperative PNI and prognosis of RCC were systemically reviewed and a meta-analysis method was performed to further evaluate the pooled prognostic value of PNI in RCC.267 (38.47%) RCC patients had low PNI according to the cut off value (49.08). Low PNI was associated with poor OS (P < .001) and RFS (P < .001), respectively. In the multivariate Cox analysis, PNI was identified to be an independent prognostic factor for OS (hazard ratio [HR] = 2.13, 95%CI: 1.25–3.62, P = .005). Compared to other nutritional indexes, this risk correlation of PNI is better than that of geriatric nutritional risk index (GNRI; HR = 1.19; P = .531), while is no better than that of neutrophil–lymphocyte ratio (NLR; 1/HR = 2.56; P < .001) and platelet–lymphocyte ratio (PLR; 1/HR = 2.85; P < .001) respectively. Meanwhile, additional 4785 patients from 6 studies were included into pooled analysis. For RCC patients who underwent surgery, low preoperative PNI was significantly associated with worse OS (pooled HR = 1.57, 95%CI: 1.37–1.80, P < .001) and worse RFS (pooled HR = 1.69, 95%CI: 1.45–1.96, P < .001). Furthermore, low PNI (<41–51) was also significantly associated with poor OS (HR = 1.78, 95%CI: 1.26–2.53 P < .05) and poor RFS (HR = 2.03, 95%CI: 1.40–2.95, P < .05) in advanced cases treated with targeted therapies.The present evidences show that PNI is an independent prognostic factor in RCC. Low PNI is significant associated with poor prognosis of RCC patients.     

Prognostic value of metabolic parameters measured by pretreatment dual-time-point 18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with intrahepatic or perihilar cholangiocarcinoma: A STROBE study

The purpose of this study was to determine the glucose metabolism at delay phase measured by pretreatment dual-time-point ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/ computed tomography (CT) provides prognostic information independent of well-known prognostic factors in patients with intrahepatic or perihilar cholangiocarcinoma (ICC or PCC).From July 2012 to December 2017, 55 patients (men 27, women 28, mean age 68 ± 11 years) with pathologically proven ICC or PCC were enrolled in this retrospective study. The dual-time-point ¹⁸F-FDG PET/CT as part of a staging workup was performed in all patients. The patient''s data includes age, sex, serum CA19-9, presence of LN or distant metastasis, early SUVmax (early maximum standardized uptake value [eSUV]), delay SUVmax (delay maximum standardized uptake value [dSUV]), retention index of SUVmax (percent change of maximum standardized uptake values [ΔSUV]), neutrophil to lymphocyte ratio (NLR) and histopathology including pCEA, p53, Ki-67 index. The analysis of the relationship between metabolic parameters and survival was done using the Kaplan–Meier curve and Cox proportional hazards regression model.Median survival for all patients was 357 days. Median early and delay SUVmax was 5.2 (range: 2.0–21.4) and 6.5 (range 2.7–24.5), respectively. The overall survival was found to be significantly related to eSUV, dSUV, ΔSUV, age, serum CA19-9 and NLR in univariate analysis. In multivariate analysis, dSUV (P = .014, 95%CI; 1.30–10.7, HR 3.74) and ΔSUVmax (P = .037, 95%CI; 1.05–6.12, HR 2.5) were independent factors of overall survival. Kaplan–Meier curve analysis clearly showed the significant difference of overall survival between 2 groups (high eSUV, low eSUV + high ΔSUV vs low eSUV and ΔSUV, P < .001) among the comparisons of the SUV parameters on FDG PET. In the receiver operating characteristic analysis using combinations of the SUV parameters, the 2 groups [eSUV + ΔSUV (P = .0001, area under the curve [AUC] 0.68) and dSUV + ΔSUV (P = .0002, AUC 0.71)] showed significantly larger AUC than the other groups applying eSUV or dSUV alone (AUC 0.61 and AUC 0.68).dSUV and ΔSUV on pretreatment dual-time-point ¹⁸F-FDG PET/CT can be useful parameters in the prediction of survival in patients with ICC or PCC.     

Necrosis on pre-radiotherapy 18F-FDG PET/CT is a predictor for complete metabolic response in patients with non-small cell lung cancer

To investigate necrosis on pre-radiotherapy (RT) ¹⁸F-FDG PET/CT (PET_NECROSİS) as a predictor of complete metabolic response (CMR) in patients with non-small cell lung cancer (NSCLC).We evaluated patients with inoperable stage I–III NSCLC who underwent pre- and post-radiotherapy ¹⁸F-FDG PET/CT. The relationship between CMR and PET_NECROSIS, SUVmax, gross tumor volume calculated with ¹⁸F-FDG PET/CT (GTV_PET-CT), tumor size, histology, metabolic tumor volume (MTV), and RT dose was assessed using logistic regression analysis. To evaluate necrosis on ¹⁸F FDG PET/CT, we drew a region of interest (ROI) in the area showing visually very low/or no fluorodeoxyglucose (FDG) uptake on PET images. If the SUVmax was lower than the blood pool SUVmax and showed significantly lower attenuation (10–30 Hounsfield units [HU]) from the surrounding tissue on non-intravenous contrast-enhanced low-dose correlative CT, we defined it as necrotic (PET_NECROSİS).Fifty-three patients were included in this study. The mean age was 68.1 ± 9.8 years. Twenty-one patients had adenocarcinoma, and 32 had squamous cell carcinoma. All parameters were independent of histologic status. Multivariate logistic regression analysis showed that SUVmax ≤11.6 vs >11.6, (P = .003; OR, 7.670, 95CI%: 2.013–29.231) and PET_NECROSİS absence/presence were independent predictors for CMR (P = .028, OR: 6.704, 95CI% 1.214–30.394).The necrosis on ¹⁸F FDG PET/CT and SUVmax > 11.6 could be an imaging marker for the complete metabolic response after definitive chemoradiotherapy or definitive RT alone in patients with NSCLC.     

Overexpression of MMP14 predicts the poor prognosis in gastric cancer: Meta-analysis and database validation

Background:Plenty of studies have showed matrix metalloproteinase 14 (MMP14) expression might be associated with the prognosis of gastric cancer (GC). However, no definite conclusion has been obtained for the contradictory results.Methods:We searched PubMed, Web of science, Embase, and Cochrane library for eligible studies. The association between MMP14 expression and prognostic outcomes of GC was evaluated. Hazard ratio (HR) and 95% confidence interval (CI) were integrated to show the effect of MMP14 expression on the overall survival (OS) or recurrence-free survival (RFS). Data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) was used to validate the association of MMP14 expression with OS or RFS in GC. A brief bioinformatics analysis was also performed to determine the prognostic role of MMP14 expression in GC.Results:High MMP14 expression was associated with shorter OS compared to low MMP14 expression in GC (HR = 1.95, P < .01). Patients with high MMP14 expression tended to have worse differentiation (P = .03), deeper tumor invasion (P < .01), earlier lymph node metastasis (P < .01), earlier distant metastasis (P < .01) and more advanced clinical stage (P < .01) compared to those with low MMP14 expression. The data from TCGA and GEO showed MMP14 was overexpressed in tumor tissues compared to normal tissues (P < .05), and high MMP14 expression was significantly related to shorter OS (HR = 1.70, 95% CI = 1.32–2.20, P < .01) and RFS (HR = 1.45, 95% CI = 1.15–1.83, P < .01) compared to low MMP14 expression in GC. Expression of MMP14 was linked to functional networks involving the biological process, metabolic process, response to stimulus, cell communication and so on. Functional network analysis suggested that MMP14 regulated the protein digestion and absorption, extracellular matrix receptor interaction, focal adhesion, ribosome, spliceosome, and so on.Conclusion:High MMP14 expression was associated with worse prognosis of GC compared to low MMP14 expression. MMP14 expression could serve as a prognostic factor and potential therapeutic target of GC.     

Predictive Significance of a New Prognostic Score for Patients With Diffuse Large B-Cell Lymphoma in the Interim-Positron Emission Tomography Findings

We hypothesized that the objective treatment response of patients with diffuse large B-cell lymphoma (DLBCL) was affected by many factors such as pathophysiological, biological, and pharmaceutical mechanisms. This retrospective study aimed to evaluate the predictive significance of clinical prognostic factors and interim fluorine-18-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT), and to find a new prognostic predictor significantly associated with DLBCL patients’ outcome. A total of 105 adult patients with DLBCL were reviewed. Each patient underwent an interim ¹⁸F-FDG PET/CT scan after the second chemotherapy cycle. The visual method based on the Deauville 5-point scale was used to evaluate the interim-PET/CT scans. The relationships among the prognostic factors, the 3-year progression-free survival (PFS) rate and overall survival (OS) rate were analyzed with Kaplan–Meier plots. The predictive value of the newly constructed prognostic score was analyzed with multivariate analysis (Cox proportional hazard regression model). The visual analysis showed statistically significant differences in both PFS and OS between the patients with a negative interim-PET/CT and those with a positive interim-PET/CT. Advanced age, advanced stage, and DLBCL subtype were also significantly associated with outcome. A new prognostic score that composed of the above 4 factors was obtained. New prognostic score stratified patients into 4 risk groups with 3-year PFS of 98.5%, 73.9%, 11.1%, and 0%, and 3-year OS of 100%, 91.3%, 55.6%, and 0% (P < 0.001 for PFS and OS). Multivariate analysis showed that the new prognostic score had the greatest ability to predict relapse (P < 0.001) and death (P < 0.001). In DLBCL patients, interim ¹⁸F-FDG PET/CT can provide significant independent prognostic information. Our work illustrates that the new prognostic score has the strongest potential for accurately prognostication, for stratification in clinical trials, and for design of novel strategies for DLBCL patients in the high-risk group.     

An Ultra-Deep Targeted Sequencing Gene Panel Improves the Prognostic Stratification of Patients With Advanced Oral Cavity Squamous Cell Carcinoma

An improved prognostic stratification of patients with oral cavity squamous cell carcinoma (OSCC) and pathologically positive (pN+) nodes is urgently needed. Here, we sought to examine whether an ultra-deep targeted sequencing (UDT-Seq) gene panel may improve the prognostic stratification in this patient group.A mutation-based signature affecting 10 genes (including genetic mutations in 6 oncogenes and 4 tumor suppressor genes) was devised to predict disease-free survival (DFS) in 345 primary tumor specimens obtained from pN+ OSCC patients. Of the 345 patients, 144 were extracapsular spread (ECS)-negative and 201 were ECS-positive. The 5-year locoregional control, distant metastases, disease-free, disease-specific, and overall survival (OS) rates served as outcome measures.The UDT-Seq panel was an independent risk factor (RF) for 5-year locoregional control (P = 0.0067), distant metastases (P = 0.0001), DFS (P < 0.0001), disease-specific survival (DSS, P < 0.0001), and OS (P = 0.0003) in pN+ OSCC patients. The presence of ECS and pT3–4 disease were also independent RFs for DFS, DSS, and OS. A prognostic scoring system was formulated by summing up the significant covariates (UDT-Seq, ECS, pT3–4) separately for each survival endpoint. The presence of a positive UDT-Seq panel (n = 77) significantly improved risk stratification for all the survival endpoints as compared with traditional AJCC staging (P < 0.0001). Among ECS-negative patients, those with a UDT-Seq-positive panel (n = 31) had significantly worse DFS (P = 0.0005) and DSS (P = 0.0002). Among ECS-positive patients, those with a UDT-Seq-positive panel (n = 46) also had significantly worse DFS (P = 0.0032) and DSS (P = 0.0098).Our UDT-Seq gene panel consisting of clinically actionable genes was significantly associated with patient outcomes and provided better prognostic stratification than traditional AJCC staging. It was also able to predict prognosis in OSCC patients regardless of ECS presence.     

Thymosin alpha-1 therapy improves postoperative survival after curative resection for solitary hepatitis B virus-related hepatocellular carcinoma: A propensity score matching analysis

Thymosin alpha-1 (Tα1) is an immunomodulatory and antiviral agent with potential effects on chronic hepatitis B and liver cancer. Its impact on solitary hepatocellular carcinoma (HCC) remains controversial, so we aimed to investigate the efficacy of Tα1 in solitary HBV-related HCC patients after curative resection.Between May 2010 and April 2016, 468 patients with solitary HBV-related HCC after curative resection were analyzed. Propensity score matching (PSM) was used to minimize confounding variables. Risk factors were identified by the Cox proportional hazards model. Recurrence-free survival (RFS) rates, overall survival (OS) rates, immunological, and virologic response were compared.The median follow up was 60.0 months. Immunological response improved in the Tα1 group compared with the control group (P < .001) but the virologic response was similar between 2 groups after 24 months. Patients with Tα1 therapy had better RFS and OS before (P = .018 and P < .001) and after (P = .006 and P < .001) propensity matching. Multivariate analysis revealed that Tα1 therapy was an independent prognostic factor for both OS (P < .001, HR = 0.308, 95% CI: 0.175–0.541) and RFS (P < .001, HR = 0.381, 95% CI: 0.229–0.633).Tα1 as an adjuvant therapy improves the prognosis of solitary HBV-related HCC patients after curative liver resection.     

Cerebellum/liver index in pretherapeutic 18F-FDG PET/CT as a predictive marker of progression-free survival in follicular lymphoma treated by immunochemotherapy and rituximab maintenance

The purpose of this study was to investigate the value of the “cerebellum/ liver index for prognosis” (CLIP) as a new prognostic marker in pretherapeutic ¹⁸F-Fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) in patients with follicular lymphoma treated by immunochemotherapy and rituximab maintenance, focusing on progression-free survival (PFS).Clinicobiological and imaging data from patients with follicular lymphoma between March 2010 and September 2015 were retrospectively collected and 5-year PFS was determined. The conventional PET parameters (maximum standardized uptake value and total metabolic tumor volume) and the CLIP, corresponding to the ratio of the cerebellum maximum standardized uptake value over the liver SUVmean, were extracted from the pretherapeutic ¹⁸F-FDG PET.Forty-six patients were included. Eighteen patients (39%) progressed within the 5 years after treatment initiation. Five-year PFS was 78.6% when CLIP was >4.0 and 42.0% when CLIP was <4.0 (P = .04). CLIP was a significant predictor of PFS on univariate analysis (hazard ratio 3.1, P = .049) and was near-significant on multivariate analysis (hazard ratio 2.8, P = .07) with ECOG PS as a cofactor.The CLIP derived from pretherapeutic ¹⁸F-FDG PET seems to be an interesting predictive marker of PFS in follicular lymphoma treated by immunochemotherapy and rituximab maintenance. These results should be evaluated prospectively in a larger cohort.     

The Value of 18F-FDG PET/CT Imaging Combined With Pretherapeutic Ki67 for Early Prediction of Pathologic Response After Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer

To evaluate the value of ¹⁸F-fluorodeoxyglucose-positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) and pretherapeutic Ki67 in predicting pathologic response in locally advanced breast cancer (LABC) after neoadjuvant chemotherapy (NAC).As a training set, total 301 LABC patients treated with NAC were retrospectively analyzed to evaluate the potential predictive value of pretherapeutic Ki67 for pathologic complete response (pCR) after NAC. Another 60 LABC patients were prospectively included as a validation set to evaluate the value of Ki67 combined PET/CT as pCR predictors. Ki67 was assessed in pretherapy core needle biopsy specimens and PET/CT scans were performed at baseline (before initiating NAC), after the 2nd, and 4th cycle of NAC. Maximum standardized uptake value (SUVmax) and its changes relative to baseline (ΔSUVmax%) were used as parameters of PEC/CT.In the training set, Ki67 was a predictor of pCR to NAC, with area under the curve (AUC) of 0.624 (P = 0.003) in receiver-operating characteristic (ROC) analysis. In the validation set, Ki67 alone did not show significant value in predicting pCR in the validation set. ΔSUVmax% after then 2nd or 4th course are predictors of pCR to NAC with the AUC of 0.774 (P = 0.002) and 0.791 (P = 0.002), respectively. When combined with ΔSUVmax% after the 2nd and 4th course NAC, Ki67 increased the value of ΔSUVmax% in predicting pCR with the AUC of 0.824 (P = 0.001). Baseline SUVmax and after 2nd, 4th course NAC had no predictive value for pCR, but SUVmax after the 2nd and 4th course showed remarkable predictive value for nonpathologic response (Grade 1 in Miller-Payne Grading System) with the AUC of 0.898 (P = 0.0001) and 0.801 (P = 0.003).Both PET/CT and Ki67 can predict pCR to NAC in LABC patients in the early phases of treatment. PET/CT combined Ki67 is a better pCR predictor for response to NAC. This helps the physician to predict the probability of pCR, and facilitates the optimization of individual treatment plan in case of ineffective and/or excessive chemotherapy.     

LKB1 expression and the prognosis of lung cancer: A meta-analysis

Background:In the past few decades, many lines of evidence implicate the importance of liver kinase B1 (LKB1) as a tumor suppressor gene in the development and progression of solid tumours. However, the prognostic and clinicopathological value of LKB1 in patients with lung cancer are controversial. This article aimed to investigate the latest evidence on this question.Methods:A systematic literature searched in the PubMed, Web of Science, Embase, Cochrane library, Scopus until September 20, 2020. The association between overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS), clinicopathological features and LKB1 were analysed by meta-analysis.Results:Eleven studies including 1507 patients were included in this meta-analysis. The pooled results revealed that low LKB1 expression was significantly associated with poor overall survival (OS) (HR = 1.67, 95% CI: 1.07–2.60, P = .024) in lung cancer. However, no association was found between LKB1 expression and DFS/PFS (HR = 1.29, 95% CI: 0.70–2.39, P = .410). Pooled results showed that low LKB1 expression was associated with histological differentiation (poor vs moderate or well, OR = 4.135, 95% CI:2.524–6.774, P < .001), nodal metastasis (absent vs present, OR = 0.503, 95% CI: 0.303–0.835, P = .008) and smoking (yes vs no, OR = 1.765, 95% CI: 1.120–2.782, P = .014).Conclusion:These results suggest that low expression of LKB1 can be considered as a unfavorable prognostic biomarker for human lung cancer, which should be further researched.     

Prognostic markers compared to CD3+TIL in locally advanced nasopharyngeal carcinoma

Locally advanced nasopharyngeal carcinoma (LA-NPC) is more prevalent in some geographic regions, including Saudi Arabia. Typically, Tumor-Node-Metastasis (TNM) staging is used in NPC. However, it is inadequate to assess the prognosis of LA-NPC.Therefore, we analyzed and compared several previously reported prognostic factors in LA-NPC patients, retrospectively, including CD3+tumor-infiltrating lymphocytes (TIL) and peripheral blood hemoglobin, EBV DNA copy number, ratios of albumin-to-alkaline phosphatase ratio (AAPR), neutrophils, or platelets-to-lymphocytes (NLR, PLR). The studied cohort was 83 LA-NPC patients previously recruited for a randomized phase II trial with a different aim.Univariate cox regression analysis showed no significant correlation between any of the tested variables with disease-free survival (DFS) or overall survival (OS) with the exception of low CD3+ TIL infiltration, which correlated significantly with DFS (HR = 6.7, P = <.001) and OS (HR = 9.1, P = .043). Similarly, in a validated multivariate cox regression analysis, only low CD3+ TIL correlated significantly with DFS (HR = 7.0, P < .001 for TIL) and OS (HR = 9.4, P = .040).Among tested parameters, CD3+ TIL was the only independent prognostic marker for DFS and OS in LA-NPC patients treated with CCRT. This study supports the use of CD3+TIL, over other factors, as an independent prognostic factor in LA-NPC.     

The prognostic value of the peripheral blood cell counts changes during induction chemotherapy in Chinese patients with adult acute myeloid leukemia

To investigate the prognostic value of the circulating peripheral blood cell counts changes in acute myeloid leukemia (AML) at different time points during induction chemotherapy.We retrospectively analyzed the clinical and laboratory data of 237 newly diagnosed AML patients admitted to Fujian Medical University Union Hospital from January 2011 to December 2014.1. When primitive cells were first removed from the circulating peripheral blood, it was called peripheral blood blast clearance (PBBC). These patients were divided into two groups, according to PBBC. Statistical analysis showed that the day 5 of induction chemotherapy was a better cut-off for PBBC. PBBC≤5 days is defined as early-blast-clearance, while PBBC >6 days is delayed-blast-clearance. There was significant difference between the two groups on complete remission (CR) rate (P = .002), recurrence-free survival (RFS) (P = .026) and overall survival (OS) (P = .001). 2. Multivariate analysis suggested PBBC is an independent prognostic factor for CR, RFS, and OS in AML. Receiver operating characteristic(ROC) curve analysis showed the CR rate of patients with white blood cell count less than 1.25 × 10⁹/L was significantly higher than that of patients with white blood cell count more than 1.25 × 10 ⁹/L (P < .001) at day 5 of induction chemotherapy, but the RFS and OS was no significantly different (P > .05).The dynamics of peripheral blood blast in AML after initiation of induction chemotherapy, especially the time length to achieve PBBC, has important prognostic value for CR rate, RFS, and OS in AML patients. It is a simple and feasible method to evaluate the efficacy of AML.     

Prognostic value of EGFR and p-EGFR in nasopharyngeal carcinoma: A systematic review and meta-analysis

Purpose:To evaluate the prognostic effect and clinical significance of epidermal growth factor receptor and its phosphorlated form (EGFR/p-EGFR) in nasopharyngeal carcinoma.Methods:A systematic review and meta-analysis was designed. We visited PubMed, Embase, China National Knowledge Infrastructure Database, Database of Chinese sci-tech periodicals, WanFang Database, and China Biology Medicine disc to search for Chinese and English publications of prospective studies and retrospective studies investigating the association of EGFR/p-EGFR and nasopharyngeal carcinoma prognosis from inception to April 2021. The inclusion criteria were that the samples should be pathologically confirmed as nasopharyngeal carcinoma and the expression of EGFR/p-EGFR should be detected via immunohistochemistry; the study should analyze the prognostic significance of EGFR/p-EGFR in nasopharyngeal carcinoma; hazard ratio (HR) and 95% confidence interval (CI) should be reported in the study or could be derived from survival curves; and the outcomes of the study should include overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and distant metastasis-free survival (DMFS).Results:A total of 18 studies evaluating 1451 samples were included. For studies that reported OS as an outcome, EGFR overexpression indicated worse OS of nasopharyngeal carcinoma patients. The heterogeneity between studies was high (I² = 91%, P < .01), and a random-effect model was used to combine the effect size (HR = 1.71, 95% CI [1.21, 2.41], P < .01). Further sensitivity analysis and prespecified subgroup analysis were performed to detect the source of heterogeneity, and the results showed that the heterogeneity could not be eliminated. Publication bias assessed by funnel plots and Begg test and Egger test was low (Begg test: P = .846 and Egger test: P = .074). p-EGFR was not correlated with the OS of nasopharyngeal carcinoma patients (HR = 1.01, 95% CI [0.88, 1.15], P = .92). For studies that reported DFS, EGFR overexpression was associated with worse DFS in patients with nasopharyngeal carcinoma (HR = 2.53, 95% CI [1.84, 3.47], P < .01). For studies that reported PFS, EGFR overexpression was not correlated with the PFS of nasopharyngeal carcinoma patients (HR = 1.86, 95% CI [0.90, 3.82], P = .09). For studies that reported DMFS, EGFR overexpression was not correlated with the DMFS of nasopharyngeal carcinoma patients, and high heterogeneity between studies was detected (I² = 97%, P < .01). A random-effect model was used to combine the effect size (HR = 1.80, 95% CI [0.56, 5.76], P = .32). A sensitivity analysis was conducted. Publication bias was detected to be low (Begg test: P = .817 and Egger test: P = .954). There was no correlation between p-EGFR overexpression and DMFS in patients with nasopharyngeal carcinoma (HR = 1.20, 95% CI [0.95, 1.52], P = .12).Conclusion:In nasopharyngeal carcinoma patients, EGFR overexpression could be used as a biomarker that predicts poor OS and DFS, but not a prognostic biomarker for PFS and DMFS. The overexpression of p-EGFR was not shown to be associated with the prognosis of nasopharyngeal carcinoma patients and could not be used as a prognostic biomarker.Ethics and dissemination:This study was registered on the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), and reported as stated by the Preferred Reporting Items for Systematic reviews and Meta-Analyses. Neither ethical approval nor informed consent was required since this study was conducted based on previous publications.INPLASY registration number:INPLASY 202150010     

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.     

The relationship between NLR/PLR/LMR levels and survival prognosis in patients with non-small cell lung carcinoma treated with immune checkpoint inhibitors

Background:The relationship between neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) and the dire prognosis of non-small cell lung carcinoma patients who received immune checkpoint inhibitors (ICIs) are not known yet.Methods:We screened the articles that meet the criteria from the database. The relationship between NLR/PLR/LMR levels and the survival and prognosis of non-small cell lung cancer patients treated with ICIs was analyzed. Summarize hazard ratio (HR) with 95% confidence interval (CI) to study progression-free survival (PFS) and overall survival (OS).Results:Thirty-four studies involving 3124 patients were enrolled in the final analysis. In short, high pre-treatment NLR was related to poor OS (HR = 2.13, 95% CI:1.74–2.61, P < .001, I² = 83.3%, P < .001) and PFS (HR = 1.77, 95% CI:1.44–2.17, P < .001, I² = 79.5%, P < .001). Simultaneously, high pre-treatment PLR was related to poor OS (HR = 1.49, 95% CI:1.17–1.91, P < .001, I² = 57.6%, P = .003) and PFS (HR = 1.62, 95% CI:1.38–1.89, P < .001, I² = 47.1%, P = .036). In all subgroup analysis, most subgroups showed that low LMR was related to poor OS (HR = 0.45, 95% CI: 0.34–0.59, P < .001) and PFS (HR = 0.60, 95% CI: 0.47–0.77, P < 0.001, I² = 0.0%, P < .001).Conclusion:High pre-treatment NLR and pre-treatment PLR in non-small cell lung carcinoma patients treated with ICIs are associated with low survival rates. Low pre-treatment and post-treatment LMR are also related to unsatisfactory survival outcomes. However, the significance of post-treatment NLR and post-treatment PLR deserve further prospective research to prove.     

Serosal Invasion Strongly Associated With Recurrence After Curative Hepatic Resection of Hepatocellular Carcinoma: A Retrospective Study of 214 Consecutive Cases

The purpose of this study was to clarify the individual prognostic factors after curative and primary resection of hepatocellular carcinoma (HCC).Reliable prognostic factors and tumor staging for HCC have been required to predict an appropriate prognosis. However, in HCC, no staging system has received universal acceptance, and several tumor factors seem to relate to HCC prognosis, but they are not definitive. At present, few studies have mentioned the importance of serosal invasion as a prognostic factor.A retrospective search of our database identified 214 consecutive patients who underwent primary and curative hepatectomy for HCC at our department between January 1998 and December 2011. Risk factors for recurrence-free survival (RFS) and overall survival (OS) were analyzed with Cox proportional hazard model, Kaplan-Meier method, and log-rank tests.Multivariate analyses showed that serosal invasion (hazard ratio [HR], 2.75; P = 0.0005) and vascular invasion (HR, 1.71; P = 0.0331) were independently correlated with RFS. Serosal invasion was significantly correlated with HCC recurrence (P = 0.0230). The Kaplan–Meier method and log-rank tests revealed that the patients with serosal invasion showed significantly worse prognosis both in RFS (P < 0.0001) and OS (P = 0.0016).Serosal invasion should be regarded as a strong independent predictor for recurrence in curatively resected HCC cases.