Independent Predictor Of Overall Survival Research Articles

The sorafenib resistance-related gene signature predicts prognosis and indicates immune activity in hepatocellular carcinoma

ABSTRACT Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death worldwide. Most patients with advanced HCC acquire sorafenib resistance. Drug resistance reflects the heterogeneity of tumors and is the main cause of tumor recurrence and death.We identified and validated sorafenib resistance related-genes (SRGs) as prognostic biomarkers for HCC. We obtained SRGs from the Gene Expression Omnibus and selected four key SRGs using the least absolute shrinkage and selection operator, random forest, and Support Vector Machine-Recursive feature elimination machine learning algorithms. Samples from the The Cancer Genome Atlas (TCGA)-HCC were segregated into two groups by consensus clustering. Following difference analysis, 19 SRGs were obtained through univariate Cox regression analysis, and a sorafenib resistance model was constructed for risk stratification and prognosis prediction. In multivariate Cox regression analysis, the risk score was an independent predictor of overall survival (OS). Patients classified as high-risk were more sensitive to other chemotherapy drugs and showed a higher expression of the common immune checkpoints. Additionally, the expression of drug-resistance genes was verified in the International Cancer Genome Consortium cohort. A nomogram model with a risk score was established, and its prediction performance was verified by calibration chart analysis of the TCGA-HCC cohort. We conclude that there is a significant correlation between sorafenib resistance and the tumor immune microenvironment in HCC. The risk score could be used to identify a reliable prognostic biomarker to optimize the therapeutic benefits of chemotherapy and immunotherapy, which can be helpful in the clinical decision-making for HCC patients.

A comparative analysis of radical cystectomy with perioperative chemotherapy, chemoradiation therapy, or systemic therapy in patients with clinically advanced node-positive bladder cancer (cN2/N3).

The management of non-metastatic clinically advanced lymph nodal (cN2/N3) bladder cancer (Stage IIIB) could involve radical cystectomy, chemoradiation, or systemic therapy alone. However, a definitive comparison between these approaches is lacking. This study aims to compare the outcomes of patients undergoing radical cystectomy with pelvic lymph node dissection (RC-PLND), chemoradiation therapy (CRT) or systemic therapy (including immunotherapy) (ST) only in patients with stage IIIB bladder cancer. A retrospective analysis of the National Cancer Database for patients with stage IIIB urothelial bladder cancer was done from 2004-2019. Patients were classified as Group A: Those who received RC-PLND with perioperative chemotherapy, Group B: Those who received CRT, and Group C: Those who received only ST alone. The primary outcome was overall survival (OS). Inverse probability weighting (IPW)-adjusted Kaplan Meier curves were utilized to compare overall survival (OS) and cox multivariate regression analysis was used to identify predictors for OS. Overall, 2,575 patients were identified. They were classified into Group A (n=1,278), Group B (n=317) and Group C (n=980). Compared to Group B, patients in Group A were younger (SMD=19.6%), had lower comorbidities (SMD=18.2%), had higher income (SMD=31.5%), had private insurance (SMD= 26.7%), were treated at academic centres (SMD=29.3%) and had higher percentage of N2 disease (SMD=31.1%). Using IPW-adjusted survival analysis, compared to Group C, the median OS was significantly higher in Group A (20.7 vs 14.2 months, p<0.001) and Group B (19.7 vs 14.2 months, p<0.001) but similar between Group A and Group B (20.9 vs 19.7 months, p=0.74). Both surgery (HR=0.72 (0.65-0.80), p<0.001) and CRT (0.70 (0.59-0.82), p<0.001) appeared to be independent predictors for OS on cox-regression analysis. The major limitations include bias due to retrospective analysis and non-assessment of cancer-specific survival. In stage IIIB bladder cancer with advanced lymph nodal disease, both RC and CRT offer equivalent survival benefits and are superior to systemic therapy alone.

Neutrophil-lymphocyte ratio reflects tumour-infiltrating lymphocytes and tumour-associated macrophages and independently predicts poor outcome in breast cancers with neoadjuvant chemotherapy.

The neutrophil-lymphocyte ratio (NLR) is a systemic reflection of cancer-associated inflammation and a prognostic marker for breast cancer. For the local tumour microenvironment, tumour-infiltrating lymphocytes (TILs) and tumour-associated macrophages (TAMs) are also highly correlated with breast cancer survival. This study aimed to explore the relationship between the circulating and local immune microenvironment, and to further delineate the prognostic role of NLR in breast cancer patients receiving neoadjuvant chemotherapy (NAC). A cohort of breast cancer patients receiving NAC with subsequent surgery was retrieved. Clinical data were reviewed. Histological slides andCD8 immunohistochemistry from biopsy (pre-chemotherapy) and excision (postchemotherapy) specimens were assessed for TILs and TAMs. A total of 146 patients were included. There was a significant positive correlation between pre- and postsurgery NLR at a cut-off of 2.6 (median pre-chemotherapy NLR) (P < 0.001). NLR pre-chemotherapy was associated positively with necrosis on biopsy (P = 0.027) and excision (P = 0.021) and TAMs on excision (P = 0.049). NLR 1 year postsurgery was associated with high tumour stage (P = 0.050) and low histological grade (P = 0.008). TIL count was lower in NLR-high cases at almost all time-points by histological assessment and CD8 immunostaining (P < 0.050). In multivariate analysis, postsurgery NLR is an independent predictor for overall survival [OS; hazard ratio (HR) = 9.524, P < 0.001], breast cancer-specific survival (BCSS) (HR = 10.059, P = 0.001) and disease-free survival (DFS; HR = 2.824, P = 0.016). The association between NLR with tumour necrosis, TAMs and TILs illustrates an interaction between the circulating and local immune microenvironment. Late NLR is a strong indicator of outcome and may be useful for prognostication and disease monitoring.

Surgical outcomes and predictors of overall survival of stage I-III appendiceal adenocarcinoma: Retrospective cohort analysis of the national cancer database

BackgroundThis study aimed to determine predictors of overall survival (OS) after surgical treatment of stage I-III appendiceal adenocarcinoma and compare the outcomes of partial colectomy and hemicolectomy. MethodsA retrospective analysis of the U.S. National Cancer Database (NCDB) including patients who underwent surgery for stage I-III appendiceal adenocarcinoma between 2005 and 2019 was conducted. A propensity-score matched analysis was undertaken to compare the outcomes of partial and hemicolectomy and multivariate analysis was performed to determine predictive factors of OS. The main outcome was OS and its independent predictors. Results2607 patients (51.6 % male) with a mean age of 61.6 ± 13.9 years were included. 61.7 % of patients underwent hemicolectomy while 31.7 % underwent partial colectomy. After matching, partial colectomy, and hemicolectomy had similar OS (117.3 vs 117.2 months; p = 0.08), positive resection margins, short-term mortality, and 30-day readmission. The hemicolectomy group was associated with more examined lymph nodes and longer hospital stays. Older age (HR: 1.047, p < 0.0001), rural residence area (HR: 3.6, p = 0.025), higher Charlson score (HR: 1.6, p = 0.016), signet-ring cell carcinoma (HR: 2.37, p = 0.009), adjuvant systemic treatment (HR: 1.55, p = 0.015), positive surgical margins (HR: 1.83, p = 0.017), positive lymph nodes number (HR: 1.09, p < 0.0001), and examined lymph nodes number (HR: 0.962, p = 0.001) were independent predictors of OS. ConclusionsPartial colectomy and hemicolectomy had similar OS and clinical outcomes. Older age, rural residence, higher Charlson score, signet-ring pathology, adjuvant systemic treatment, positive surgical margins, positive lymph node number, and examined lymph node number were independent predictors of OS.

Can Platelet-to-Lymphocyte Ratio (PLR) and Neutrophil-to-Lymphocyte Ratio (NLR) Help Predict Outcomes of Patients With Recurrent Glioblastoma?

In patients with recurrent glioblastoma, very little data are available regarding the prognostic value of platelet-to-lymphocyte (PLR) and neutrophil-to-lymphocyte (NLR) ratios. This study investigated potential associations between PLR or NLR and treatment outcomes. PLR and NLR at diagnosis of recurrence plus 10 additional characteristics were retrospectively analyzed for associations with progression-free survival (PFS) and overall survival (OS) in 75 patients with recurrent glioblastoma. On multivariate analyses, maximal cumulative diameter of recurrent lesion(s) <40 mm (p=0.015) and systemic therapy (p<0.001) were associated with improved PFS. On multivariate analysis of OS, improved outcomes were significantly associated with PLR ≤150 (p=0.029), maximal cumulative diameter <40 mm (p=0.030), and systemic therapy (p=0.010). In addition to other characteristics, PLR at the time of recurrence was identified as an independent predictor of OS in patients with recurrent glioblastoma. PLR may be useful when designing personalized treatment approaches or clinical trials.

Predictive Value of Peripheral Blood Eosinophil Count on the Efficacy of Treatment with Camrelizumab in Combination with Lenvatinib in Patients with Advanced Hepatitis B-Associated Hepatocellular Carcinoma.

Objective: To examine the effects of peripheral blood eosinophil (EOS) count and its dynamic alterations on the treatment efficacy and prognosis of patients with advanced hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) receiving camrelizumab combined with lenvatinib (C + L) therapy. Methods: A retrospective analysis was performed on 200 patients with advanced HBV-HCC who were admitted to two centers from January 2018 to August 2023 and treated with C + L. EOS, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were determined before C + L treatment (EOS0, NLR0, and PLR0) and after three cycles of treatment (EOS3, NLR3, and PLR3). The area under the curve was calculated using the receiver operating characteristic (ROC) curve. NLR and PLR served as references to analyze the effect of differences in EOS in predicting the survival efficacy of patients with HBV-HCC treated using C + L. The independent risk factors affecting progression-free survival (PFS) and overall survival (OS) were analyzed using univariate and multivariate Cox proportional risk models. Results: The ROC curve revealed that the predictive value of EOS3 was better than those of NLR3 and PLR3 for the long-term treatment efficacy of patients with intermediate and advanced HBV-HCC receiving C + L. Statistically significant differences were observed between groups with different levels of EOS0 and EOS3 and the evaluation of treatment efficacy after 3 weeks (P < 0.05). The median PFS of the high-EOS0 group was higher than that of the low-EOS0 group (P = 0.027); median PFS of the high EOS3 group was higher than that of the low EOS3 group (P = 0.018); median OS of the high EOS0 group was higher than that of the low EOS0 group (P = 0.032); median OS of the high EOS3 group was higher than that of the low EOS3 group (P < 0.0001). Multifactorial Cox analysis revealed that EOS3 was an independent predictor of PFS and that EOS0 was an independent predictor of OS (P < 0.05). Conclusion: EOS may be an ideal indicator for predicting the treatment efficacy and prognosis of patients with advanced HBV-HCC receiving C + L.

Validation of the CRAFITY score for predicting prognosis in patients with hepatocellular carcinoma undergoing transarterial chemoembolization combined with systemic therapy

BackgroundThe CRAFITY score can predict survival and radiological response to systemic front-line treatment in patient with hepatocellular carcinoma (HCC). AimsIn this study, we aimed to externally validate the CRAFITY score and compare it with other simple prognostic models in patients with unresectable HCC who underwent transarterial chemoembolization (TACE) combined with systemic therapies. MethodsPatients with unresectable HCC who underwent TACE combined with tyrosine kinase inhibitors (TKIs), with or without immune checkpoint inhibitors (ICIs), were retrospectively analyzed to determine whether the CRAFITY score can predict overall survival (OS) through multivariate analysis and Kaplan‒Meier curves. Prediction of 3- and 6-month objective response rates (ORRs) was validated by the area under the curve (AUC). ResultsAmong 147 patients with unresectable HCC, 113 received TACE ​+ ​TKI and 34 received TACE ​+ ​TKI ​+ ​ICI. The CRAFITY score was identified as an independent predictor for OS (P ​< ​0.001) and showed a good ability to categorize all included patients into low-, moderate-, and high-risk groups (P ​< ​0.001). For predicting the 3- and 6-month ORRs, the CRAFITY score exhibited poor performance, with AUCs of 0.555 and 0.515, respectively. ConclusionThe CRAFITY score is effective in predicting OS but demonstrates limited accuracy in predicting 3- and 6-month ORRs for patients with unresectable HCC undergoing TACE combined with systemic therapies.

Predicting epithelial ovarian cancer prognosis: correlation of posttreatment 18F-fluorodeoxyglucose positron emission tomography-computed tomography metabolic parameters, serum carbohydrate antigen, and human epididymis protein levels with overall survival.

Identifying reliable prognostic indicators can aid in improving patient care. The aim of this study was to establish the association of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) whole-body metabolic parameters, serum carbohydrate antigen 125 (CA125), and human epididymis protein 4 (HE4) with overall survival (OS) in patients with epithelial ovarian cancer (EOC) after surgery combined with platinum-based chemotherapy. From May 2014 to May 2019, a total of 79 patients with EOC who underwent posttreatment 18F-FDG PET/CT in the First Affiliated Hospital of Chongqing Medical University were included. Clinical data and laboratory indicators were obtained. The whole-body maximum standardized uptake value (WBSUVmax), whole-body metabolic tumor volume (WBMTV), and whole-body total lesion glycolysis (WBTLG) were measured and calculated on 18F-FDG PET/CT. The follow-up was conducted until February 2023, and the endpoint was death from any cause. Pearson correlation analysis, Kaplan-Meier, and Cox proportional regression were used in this study. The PET-positive (PET-P) patients had significantly decreased OS based on either Kaplan-Meier survival analysis (P<0.001) or univariate Cox regression analysis [hazard ratio (HR) =40.177, 95% confidence interval (CI): 2.690-600.134; P=0.007]. "Ln" is a logarithmic transformation with a base of "e" (natural logarithm). LnWBMTV, lnWBTLG, and therapy after PET were independent predictors of OS in a cohort of 63 PET-P patients. The difference in OS between groups sorted by the median WBMTV (4.16; P<0.001) and WBTLG (14.71; P<0.001) was statistically significant. There were statistically significant differences in CA125 and HE4 levels between patients in the PET-P and PET-negative (PET-N) groups (P<0.001). In the PET-P patient cohort, serum HE4 levels were substantially correlated with WBMTV and WBTLG. Kaplan-Meier survival analysis suggested a reduction in OS after treatment in patients with EOC positive for CA125, HE4, and PET (P<0.001). Post-PET/CT treatment strategy, WBMTV, and WBTLG demonstrated significant prognostic utility in predicting posttreatment OS in patients with EOC. Patients who tested positive for both tumor markers CA125 and HE4 and had a positive PET scan demonstrated a significantly poorer prognosis in terms of posttreatment OS.

Evaluation of Five Prognostic Scores in Patients Receiving Chemoradiation for Primary Glioblastoma Multiforme.

Prognostic factors can facilitate treatment personalization in patients with glioblastoma multiforme (GBM). This study investigated different Glasgow prognostic scores (GPS) and the LabBM score in patients with GBM receiving chemoradiation following resection or biopsy. Four GPS versions, LabBM score, and 10 other factors were retrospectively investigated for progression-free survival (PFS) and overall survival (OS) in 86 patients. GPS versions included original GPS (oGPS), modified GPS (mGPS), high-sensitivity mGPS (HS-mGPS), and high-sensitivity oGPS (HS-oGPS). On multivariate analysis, higher oGPS was significantly associated with worse OS (p=0.006). On univariate analyses, trends were found for associations between higher mGPS and worse OS (p=0.098) and between higher LabBM scores and worse PFS (p=0.059). The oGPS was an independent predictor of OS in patients receiving chemoradiation for GBM and can help personalizing the treatment for these patients. The LabBM score may be useful for predicting PFS.

Prognostic model for unresectable hepatocellular carcinoma treated with dual PD-1 and angiogenesis blockade therapy

Background and aimsDual programmed death 1 (PD-1) and angiogenesis blockade therapy is a frontline treatment for hepatocellular carcinoma (HCC). An accepted model for survival prediction and risk stratification in individual...

CMTM6: A Critical Prognostic Indicator in Non-Small Cell Lung Cancer.

While CKLF-like MARVEL transmembrane domain containing 6 (CMTM6)'s role in stabilizing PD-L1 and immune evasion within tumors is established, its expression in lung cancer tissue and adjacent macrophages remains uncertain. The study aimed to elucidate this ambiguity by investigating CMTM6's role in non-small cell lung cancer (NSCLC) prognosis. Employing immunohistochemical staining on 141 NSCLC and 110 adjacent normal lung tissue samples, CMTM6 expression was evaluated using the HSCORE system. Interestingly, NSCLC exhibited significantly higher CMTM6 levels (161.04±86.60) compared to normal tissues (71.20±45.10) (p < 0.001), detected not only in cancer cells but also in macrophages, lymphocytes, and nearby bronchial epithelial cells. Stratifying patients by CMTM6 levels unveiled a correlation between heightened expression and poorer overall survival (p = 0.003), alongside a link to tumor-infiltrating lymphocytes (TIL) (p = 0.037), especially in cases with increased TIL. Multivariate analysis identified CMTM6 as an independent predictor of overall survival (p = 0.009), implying that elevated CMTM6 expression in NSCLC might signify an adverse prognostic marker for patient outcomes.

Safety and Efficacy of Lenvatinib in Very Old Patients with Unresectable Hepatocellular Carcinoma.

Data concerning the use of lenvatinib in very old patients (≥ 80years) are limited, although the incidence of hepatocellular carcinoma (HCC) in this patient population is constantly increasing. This analysis aimed to evaluate the efficacy and safety of lenvatinib in a large cohort of very old patients (≥ 80years) with unresectable HCC. The study was conducted on a cohort of 1325 patients from 46 centers in four Western and Eastern countries (Italy, Germany, Japan, and the Republic of Korea) who were undergoing first-line treatment with lenvatinib between July 2010 and February 2022. Patients were stratified according to age as very old (≥ 80years) and not very old (< 80years). The median overall survival (OS) was 15.7 months for patients < 80years old and 18.4months for patients ≥ 80years old [hazard ratio (HR) = 1.02, 95% confidence interval (CI) 0.84-1.25, p = 0.8281]. Median progression free survival (PFS) was 6.3months for patients < 80years old and 6.5months for patients ≥ 80years old (HR = 1.07, 95% CI 0.91-1.25, p = 0.3954). No differences between the two study groups were found in terms of disease control rate (DCR; 80.8% versus 78.8%; p = 0.44) and response rate (RR; 38.2% versus 37.9%; p = 0.88). Patients < 80years old experienced significantly more hand-foot skin reaction (HFSR) grade ≥ 2 and decreased appetite grade ≥ 2. Conversely, patients ≥ 80years old experienced significantly more fatigue grade ≥ 2. In the very old group, parameters associated with prognosis were AFP, albumin-bilirubin (ALBI) grade, Barcelona Clinic Liver Cancer (BCLC), and Child-Pugh score. BCLC stage was the only independent predictor of overall survival (OS; HR = 1.59, 95% CI 1.11-2.29, p = 0.01115). Our study highlights the same efficacy and safety of lenvatinib between very old and not very old patients.

Efficacy and safety of raltitrexed-eluting CalliSpheres® bead transarterial chemoembolization in patients with intermediate-stage hepatocellular carcinoma: a single-arm, prospective study.

The most common loadable chemotherapeutic drugs in drug-eluting bead transarterial chemoembolization (DEB-TACE) include doxorubicin, epirubicin, etc. CalliSpheres® beads have exhibited efficient loadability and eluting characteristics for raltitrexed as well as in vitro and animal experiments. However, the efficacy and safety of raltitrexed-loaded DEB-TACE in patients with intermediate-stage hepatocellular carcinoma (HCC) remain unclear. To assess the efficacy and safety of raltitrexed-loaded DEB-TACE in patients with intermediate-stage HCC. The study was conducted as a single-arm prospective study. This study was a prospective, single-arm trial conducted between June 2019 and June 2022. CalliSpheres® beads loaded with raltitrexed were used in the DEB-TACE procedure. The follow-up lasted for at least 1 year or until death. The primary endpoint was overall survival (OS), and the secondary endpoints were time to progression (TTP), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). The 6-month ORR and disease control rates were 90.1% and 93.8%, respectively. The median OS was 33.0 months. The 1-, 2-, and 3-year survival rates were 95.1%, 82.1%, and 43.6%, respectively. Child-Pugh class and bilobar disease occurrence were identified as independent OS predictors. The median TTP and PFS were 22.7 and 19.8 months, respectively. Eleven (11.5%) patients experienced at least one grade 3 AE, and serious AEs were reported in five participants (5.2%). No patient experienced grade 4 or 5 AEs. Raltitrexed-loaded DEB-TACE is feasible, safe, and effective in patients with intermediate-stage HCC. This trial was registered at www.chictr.org.cn under the identifier: 1900024097 on 25 June 2019.

Preoperative Serum Cystatin C as an Independent Prognostic Factor for Survival in Patients with Renal Cell Carcinoma.

Purpose: This study aims to evaluate the prognostic significance of preoperative serum cystatin C (Cys-C) in patients with renal cell carcinoma (RCC). Methods: We analyzed clinicopathological data and follow-up information of 624 RCC patients who underwent partial or radical nephrectomy at our institution. The optimal cutoff value of Cys-C was determined using X-tile software. Survival outcomes, including overall survival (OS) and cancer-specific survival (CSS), were evaluated using the Kaplan-Meier method and log-rank test. To avoid overfitting and collinearity, we used LASSO-based multivariable Cox regression analysis to identify independent predictors of OS and CSS. The predictive accuracy of the established model, including preoperative serum Cys-C, was evaluated using the time-dependent receiver operating characteristic (ROC) curves and the area under the curve (AUC). Results: The median follow-up period was 40 months. The optimal cutoff value of preoperative serum Cys-C levels was 0.95 mg/L. Compared with the low Cys-C group, patients in the high Cys-C group had significantly shorter OS and CSS. Multivariable Cox regression analysis indicated that elevated preoperative serum Cys-C level was an independent adverse predictor for RCC patients post-nephrectomy. After adjusting for all covariates, high preoperative serum Cys-C level was associated with worse OS (hazard ratio [HR]: 2.254; 95% confidence interval [CI]: 1.144, 4.439; P = 0.019) and CSS (HR: 3.621; 95% CI: 1.386, 9.456; P = 0.009). Time-dependent ROC analysis demonstrated that our model, including preoperative serum Cys-C, performed well in predicting accuracy of survival. Conclusions: Preoperative serum Cys-C level is an effective prognostic indicator for OS and CSS in RCC patients undergoing nephrectomy.

Survival Predictive Nomograms for Non-Surgical Brain Metastases Patients From Non-Small Cell Lung Cancer Receiving Radiotherapy: A Population-Based Study.

A high number of Non-Small Cell Lung Cancer (NSCLC) patients with brain metastasis who have not had surgery often have a negative outlook. Radiotherapy remains a most common and effective method. Nomograms were developed to forecast the cancer-specific survival (CSS) and overall survival (OS) in NSCLC individuals with nonoperative brain metastases who underwent radiotherapy. Information was gathered from the Surveillance, Epidemiology, and End Results (SEER) database about patients diagnosed with NSCLC who had brain metastases not suitable for surgery. Nomograms were created and tested using multivariate Cox regression models to forecast CSS and OS at intervals of 1, 2, and 3years. The research involved 3413 individuals diagnosed with NSCLC brain metastases who had undergone radiotherapy but had not experienced surgery. These participants were randomly divided into two categories. The analysis revealed that gender, age, ethnicity, marital status, tumor location, tumor laterality, tumor grade, histology, T stage, N stage, chemotherapy, tumor size, lung metastasis, bone metastasis, and liver metastasis were significant independent predictors for OS and CSS. The C-index for the training set for predicting OS was .709 (95% CI, .697-.721), and for the validation set, it was .705 (95% CI, .686-.723), respectively. The C-index for predicting CSS was .710 (95% CI, .697-.722) in the training set and .703 (95% CI, .684-.722) in the validation set, respectively. The nomograms model, as suggested by the impressive C-index, exhibits outstanding differentiation ability. Moreover, the ROC and calibration curves reveal its commendable precision and distinguishing potential. For the first time, highly accurate and reliable nomograms were developed to predict OS and CSS in NSCLC patients with non-surgical brain metastases, who have undergone radiotherapy treatment. The nomograms may assist in tailoring counseling strategies and choosing the most effective treatment method.

Impact of Recombinant Granulocyte Colony-Stimulating Factor During Neoadjuvant Therapy on Outcomes of Resected Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by chronic inflammation and a tolerogenic immune response. The granulocyte colony-stimulating factor (G-CSF)-neutrophil axis promotes oncogenesis and progression of PDAC. Despite frequent use of recombinant G-CSF in the management and prevention of chemotherapy-induced neutropenia, its impact on oncologic outcomes of patients with resected PDAC is unclear. This cohort study assessing the impact of G-CSF administration was conducted on 351 patients with PDAC treated with neoadjuvant therapy (NAT) and pancreatic resection at a high-volume tertiary care academic center from 2014 to 2019. Participants were identified from a prospectively maintained database and had a median follow-up of 45.8 months. Patients receiving G-CSF (n=138; 39.3%) were younger (64.0 vs 66.7 years; P=.008), had lower body mass index (26.5 vs 27.9; P=.021), and were more likely to receive 5-FU-based chemotherapy (42.0% vs 28.2%; P<.0001). No differences were observed in baseline or clinical tumor staging. Patients receiving G-CSF were more likely to have an elevated (>5.53) post-NAT neutrophil-to-lymphocyte ratio (45.0% vs 29.6%; P=.004). G-CSF recipients also demonstrated higher circulating levels of neutrophil extracellular traps (+709 vs -619 pg/mL; P=.006). On multivariate analysis, G-CSF treatment was associated with perineural invasion (hazard ratio [HR], 2.65; 95% CI, 1.16-6.03; P=.021) and margin-positive resection (HR, 1.67; 95% CI, 1.01-2.77; P=.046). Patients receiving G-CSF had decreased overall survival (OS) compared with nonrecipients (median OS, 29.2 vs 38.7 months; P=.001). G-CSF administration was a negative independent predictor of OS (HR, 2.02; 95% CI, 1.45-2.79; P<.0001). In the inverse probability weighted analysis of 301 matched patients, neoadjuvant G-CSF administration was associated with reduced OS. In patients with localized PDAC receiving NAT prior to surgical extirpation, G-CSF administration may be associated with worse oncologic outcomes and should be further evaluated.

Circumferential resection margin positivity due to direct or indirect tumour involvement in rectal cancer - a call for better stratification.

A positive circumferential resection margin (CRM) after rectal cancer surgery, which can be the result of direct or indirect tumour involvement, has consistently been associated with increased local recurrence and poorer survival. However, little is known of the differential impact of the mode of tumour involvement on outcomes. 1460 consecutive patients undergoing rectal cancer resection between 2003 and 2018 were retrospectively assessed. Histopathology reports for patients with a positive CRM were reviewed to determine cases of direct (R1-tumour) or indirect tumour involvement (R1-other). Disease-free survival (DFS) and overall survival (OS) were assessed by Kaplan-Meier analysis. The role of the mode of CRM positivity was examined by univariate and multivariate Cox proportional hazards models. Eighty-five patients had an R1 resection due to CRM involvement (5.8%). Of those, 69 were due to direct tumour involvement, while 16 were from indirect causes. Kaplan-Meier analysis revealed that R1-other was associated with increased OS (hazard ratio 0.40, log-rank P = 0.006) and DFS (P = 0.043). Multivariate regression confirmed that the mode of CRM positivity was an independent predictor of OS. More interestingly, the patterns of recurrence were different between the two groups, with R1-tumour leading to significantly more local recurrence (P = 0.04). Our data strongly suggests that direct tumour involvement of the CRM confers worse prognosis after rectal cancer surgery. Importantly, differences in the site and frequency of recurrences make a case for better stratification of patients with a positive CRM to guide treatment decisions.

SFXN1 as a potential diagnostic and prognostic biomarker of LUAD is associated with 18F-FDG metabolic parameters

BackgroundSideroflexin 1 (SFXN1) has been discovered as a novel tumor marker for lung adenocarcinoma, but data on its importance in the development of lung adenocarcinoma is still limited. This study evaluated the correlation between SFXN1 and parameters related to 18F-flurodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT), and further explored the role of SFXN1 in the value-added and glycolytic processes of LUAD. MethodThe expression and prognostic value of SFXN1 mRNA in LUAD were analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data base. Retrospective analysis of 18F-FDG PET imaging and metabolic parameters in 42 patients to explore the relationship between the expression of SFXN1 and glucose metabolism levels in lung adenocarcinoma and its clinical significance. H1975 cells were selected as the in vitro research object, and the biological effects of SFXN1 on LUAD were further elucidated through Edu proliferation assay, CCK8 activity assay, wound healing experiment, and cell flow cytometry. ResultSFXN1 is highly expressed in various tumors, including LUAD, and its high expression can serve as an independent predictor of overall survival in lung adenocarcinoma. In addition, the expression of SFXN1 in LUAD was significantly correlated with 18F-FDG PET/CT parameters: maximum and average standardized uptake values (SUVmax and SUVmean), as well as total lesion glycolysis (TLG) (rho = 0.574, 0.589, and 0.338, p < 0.05), which can predict the expression of SFXN1 with an accuracy of 0.934. In vitro functional experiments have shown that knocking down SFXN1 inhibits the proliferation and migration of LUAD cells, promotes cell apoptosis, and may inhibit tumor activity by regulating the expression of glycolytic related genes SLC2A1, HK2, GPI, ALDOA, GAPDH, ENO1, PKM, and LDHA. ConclusionThe overexpression of SFXN1 is closely related to FDG uptake, and SFXN1, as a promising prognostic biomarker, may mediate the development of LUAD through the glycolytic pathway.

Significance of Preoperative Modified Nutritional Risk Index in Patients With Gastric Cancer After Curative Resection.

A new modified nutritional risk index (mNRI), calculated using serum albumin (g/l)+body mass index (BMI) [weight (kg_/height2 (m2)], is a good predictor of postoperative complications and cancer survival. However, no study has used this index in patients with gastric cancer (GC). Therefore, we aimed to investigate the clinical significance of the preoperative mNRI values in patients with GC who underwent curative resection. We examined 449 patients who underwent curative resection for GC at Kanagawa Cancer Center between 2013 and 2017. The mNRI cutoff value obtained using a receiver operating characteristic analysis was 23.31. Patients were divided into high and low mNRI groups according to the cutoff value, and the clinicopathological characteristics and outcomes were compared between the two groups. In terms of clinicopathological characteristics, the high mNRI group had a higher proportion of men, higher BMI, and a higher proportion of patients with American Society of Anesthesiologists physical status class 2/3 compared with the low mNRI group; the low mNRI group had significantly worse 5-year recurrence-free survival (RFS) and overall survival (OS) than the high mNRI group (OS, p=0.005) (OS, p=0.006; RFS, p=0.018) did. In the multivariate analysis, a low mNRI was an independent predictor of OS (p=0.006) and RFS (p=0.013). Preoperative mNRI may be a useful recurrence and prognostic biomarker in patients with GC who have undergone curative resection.

The expression of Plakoglobin in residual cancer after neoadjuvant chemotherapy for breast cancer and its prognostic impact on patients

Objective: To investigate the relationship between the expression levels of Plakoglobin protein in residual lesions after neoadjuvant chemotherapy (NAC) and the prognosis of breast cancer patients. Methods: Clinical and pathological data from 174 breast cancer patients who underwent surgery after receiving NAC at the Cancer Hospital of Chinese Academy of Medical Sciences from January 2009 to December 2017 were collected. The expression level of Plakoglobin in residual cancer lesions was evaluated by immunohistochemistry. The correlation between Plakoglobin expression level and clinicopathological features was analyzed. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard regression models were used for factor analysis. Results: Among the 174 patients, 140 had low expression of Plakoglobin, and 34 had high expression. The median disease-free survival (DFS) and overall survival (OS) in the Plakoglobin low expression group were 59.46 and 71.68 months, respectively, both of which were higher than those in the high expression group (36.58 and 47.26 months, respectively, both P<0.05). Univariate analysis showed that Plakoglobin expression, pathological N stage, lymphovascular invasion status, histological grade, Ki-67, and molecular subtypes were associated with OS (all P<0.05), while pathological N stage, histological grade, and Ki-67 were associated with DFS (all P<0.05). Multivariate analysis revealed that Plakoglobin expression (HR=2.438, 95% CI: 1.256-4.735, P=0.008) was an independent predictor for OS, and Ki-67 (HR=2.228, 95% CI: 1.316-3.773, P=0.003) was an independent predictor for DFS. Conclusion: In breast cancer patients with residual lesions after NAC, those with low Plakoglobin expression have relatively longer OS and Plakoglobin is an independent prognostic factor for OS.