Independent Factor For Survival Research Articles

Epidemiology and prognostic nomogram for locally advanced gastric signet ring cell carcinoma: A population-based study.

Gastric signet ring cell carcinoma (GSRC) represents a specific subtype of gastric cancer renowned for its contentious epidemiological features, treatment principles, and prognostic factors. To investigate the epidemiology of GSRC and establish an improved model for predicting the prognosis of patients with locally advanced GSRC (LAGSRC) after surgery. The annual rates of GSRC incidence and mortality, covering the years 1975 to 2019, were extracted from the Surveillance, Epidemiology, and End Results (SEER) database to explore the temporal trends in both disease incidence and mortality rates using Joinpoint software. The clinical data of 3793 postoperative LAGSRC patients were collected from the SEER database for the analysis of survival rates. The Cox regression model was used to explore the independent prognostic factors for overall survival (OS). The risk factors extracted were used to establish a prognostic nomogram. The overall incidence of GSRC increased dramatically between 1975 and 1998, followed by a significant downward trend in incidence after 1998. In recent years, there has been a similarly optimistic trend in GSRC mortality rates. The trend in GSRC showed discrepancies based on age and sex. Receiver operating characteristic curves, calibration curves, and decision curve analysis for 1-year, 3-year, and 5-year OS demonstrated the high discriminative ability and clinical utility of this nomogram. The area under the curve indicated that the performance of the new model outperformed that of the pathological staging system. The model we established can aid clinicians in the early prognostication of LAGSRC patients, resulting in improved clinical outcomes by modifying management strategies and patient health care.

Prognostic value of the Naples prognostic score in patients with intrahepatic cholangiocarcinoma after hepatectomy

BackgroundThe Naples Prognostic Score (NPS), integrating inflammatory and nutritional biomarkers, has been reported to be associated with the prognosis of various malignancies, but there is no report on intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the prognostic value of NPS in patients with ICC.MethodsPatients with ICC after hepatectomy were collected, and divided into three groups. The prognosis factors were determined by Cox regression analysis. Predictive efficacy was evaluated by the time-dependent receiver operating characteristic (ROC) curves.ResultsA total of 174 patients were included (Group 1: 33 (19.0%) patients; Group 2: 83 (47.7%) patients; and Group 3: 58 (33.3%) patients). The baseline characteristics showed the higher the NPS, the higher the proportion of patients with cirrhosis and Child-Pugh B, and more advanced tumors. The Kaplan-Meier curves reflect higher NPS were associated with poor survival. Multivariable analysis showed NPS was an independent risk factor of overall survival (NPS group 2 vs. 1: HR = 1.671, 95% CI: 1.022–3.027, p = 0.009; NPS group 3 vs. 1: HR = 2.208, 95% CI: 1.259–4.780, p = 0.007) and recurrence-free survival (NPS group 2 vs. 1: HR = 1.506, 95% CI: 1.184–3.498, p = 0.010; NPS group 3 vs. 1: HR = 2.141, 95% CI: 2.519–4.087, P = 0.001). The time ROC indicated NPS was superior to other models in predicting prognosis.ConclusionsNPS is a simple and effective tool for predicting the long-term survival of patients with ICC after hepatectomy. Patients with high NPS require close follow-up, and improving NPS may prolong the survival time.

Negative expression of CD117 predicted inferior OS and PFS in acute promyelocytic leukemia.

In recent years, the correlation between CD117 antigen and the prognosis of hematological malignancies has been demonstrated. However, there is limited literature on the clinical significance of CD117 antigen in acute promyelocytic leukemia (APL). The aim of this study was to retrospectively analyze the clinical features and prognostic significance of CD117 in APL. In this study, we retrospectively investigated the clinicopathological characteristics, outcome, and prognostic impact of negative CD117 expression (CD117-) in 169 APL patients treated with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) containing regimen. The median follow-up period was 63.0 months. CD117- was detected in 13 APL patients (7.7%). No significant differences were found in baseline characteristics between CD117+ and CD117- subgroups. However, compared to CD117+ APL, the incidence of early death (ED) was significantly higher in CD117- APL (p = 0.023). By multivariate analysis, CD117- was an independent adverse prognostic factor for overall survival (OS) and progression-free survival (PFS) (p = 0.022 and p = 0.014, respectively). To sum up, CD117- is associated with greater risk of ED and has the statistical power to predict inferior OS and PFS, this marker may be considered to build prognostic scores for risk-adapted therapeutic strategies in APL management.

The Prognostic Value of Proliferative Activity in Cutaneous Melanoma: A Pilot Study Evaluating the Mitotic Rate and Ki67 Index to Predict Patient Outcomes.

Proliferative activity in cutaneous melanomas can be appreciated both histopathologically by counting mitotic figures and immunohistochemically through the Ki67 index, but the prognostic value of each method is still a matter of debate. In this context, we performed a retrospective study on 33 patients diagnosed with cutaneous melanomas between 2013 and 2018 in order to evaluate progression-free survival and overall survival. Multivariate Cox proportional hazards regression was performed by considering both clinical histopathological and immunohistochemical features. The mitotic rate was significantly independently associated with both outcomes, while the Ki67 index was not an independent prognostic factor. However, the Ki67 predictive accuracy could be improved by establishing both a cut-off value and a standardized protocol for evaluating its expression. Until these desiderata are met, the mitotic rate remains superior to the Ki67 index for predicting prognosis in cutaneous melanomas, as also has the advantage of being easily interpreted in a standard histopathological examination regardless of the pathologist's experience and with no further financial expenses. Importantly, this is one of very few articles that has shown perineural invasion to be an independent prognostic factor for both progression-free survival and overall survival in cutaneous melanomas. As a consequence, this parameter should become a mandatory feature in the histopathological evaluation of cutaneous melanomas as it can improve the identification of patients who are at high risk for disease progression.

Analysis of clinical and pathological characteristics of retroperitoneal paraganglioma and associated prognostic factors.

The aim of this study is to explore the long-term prognostic risk factors associated with patients diagnosed with retroperitoneal paraganglioma (RPGL) and examine their clinical and pathological characteristics. Expressions of biomarkers were identified using immunohistochemistry (IHC) and case databases were retrospectively searched. Survival analysis was performed using Kaplan-Meier and Cox risk regression to identify the factors that influence the postoperative progression-free survival of patients with RPGL. A total of 105 patients, most of whom had tumors situated in the paraaortic region, and whose average tumor size was 8.6 cm, were enrolled in this study. The average follow-up duration was 51 months, with a mortality rate of 19% and a recurrence and metastasis rate of 41.9%. Tumors were assessed using the modified Grading system for Adrenal Pheochromocytoma and Paraganglioma (GAPP), and SDHB, S-100, and Ki-67 were stained using IHC in all cases. Out of the total cases examined, negative in SDHB expression were observed in 18.1% of cases, S-100 expression was negative in 36.2% of cases, and endovascular tumor enboluswas present in approximately 25.7% of cases. The results of the univariate analysis indicated that several factors significantly influenced the progression-free survival of patients with PGL as follow: maximum tumor diameter (>5.5 cm), tumor morphological features, tumor grading (modified GAPP score > 6), SDHB negative, S-100 negative, and expression of proliferation index Ki-67 (>3%) (X2 = 4.217-27.420, p < 0.05). The results of the multivariate analysis indicated that negative of S-100 (p = 0.021) and SDHB (p = 0.038), as well as intravascular tumor thrombus (p = 0.047) expression were independent risk factors for progression-free survival in patients. RPGL is characterized by diverse biological features and an elevated susceptibility to both recurrence and metastasis. Both SDHB and S-100 can be employed as traditional IHC indicators to predict the metastatic risk of PGL, whereas the tumor histomorphology-endovascular tumor enbolus assists in determining the metastasis risk of RPGL.

Model for end-stage liver disease-dependent prognostic capacity of platelet-to-lymphocyte ratio following liver transplantation for hepatocellular carcinoma

BackgroundTo improve liver organ allocation, the model for end-stage liver disease (MELD) score was adopted in candidates reflecting the severity of liver disease and the physical condition of patients. Inflammatory markers are prognostic factors for various cancers and play prognostic roles in patients after liver transplantation (LT) for hepatocellular carcinoma (HCC). Researchers focused more on pre-LT inflammatory markers, while the role of dynamic change of these inflammatory markers is still unknown. The purpose of this study was to estimate the prognostic value of pre-LT and post-LT inflammatory markers. Material and methodsWe collected the pre-LT complete blood count and the post-LT result with highest count of white blood cells within 48 h. Platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio and systemic immune-inflammation index were calculated, and their prognostic roles were analyzed for their MELD scores. ResultsThis retrospective two-center cohort study enrolled 290 patients after LT for HCC. Multivariate analysis identified pre-LT PLR as independent risk factor for recurrence-free survival (RFS) [HR (95%CI): 1.002 (1.000–1.003), p = 0.023]. A high pre-LT PLR or post-LT PLR were associated with poorer RFS (p < 0.001 and p = 0.004, respectively). Based on the MELD scores, the pre-LT PLR value was able to predict the RFS in high MELD group (p < 0.001) but had no predictive power in low MELD group (p = 0.076). On the contrary, the post-LT PLR value was better to predict the overall RFS value in low MELD group (p = 0.007) but could not predict the overall RFS value in high MELD group (p = 0.136). ConclusionsBoth pre-LT PLR and post-LT PLR demonstrated prognostic value in patients following LT for HCC. Monitoring PLR values based on the MELD score can improve the predictive prognosis and more effectively guide the individual decisions for the postoperative intervention.

The Clinical Role of Adjuvant Chemotherapy after Sublobar Resection for Non-Small-Cell Lung Cancer ≤ 20 mm with Lymph Node Metastases: A Propensity-Matched Analysis of the National Cancer Database.

Sublobar resection is a standard surgical procedure for small-sized non-small-cell lung cancer (NSCLC). However, the clinical role of adjuvant chemotherapy for small-sized NSCLC with pathological lymph node (LN) metastasis after sublobar resection is unknown. The National Cancer Database was queried for NSCLC patients between 2004 and 2018. Eligibility included sublobar resection with pathological LN metastasis, R0 resection, Charlson comorbidity score = 0, clinical stage T1a-b, and tumor size ≤ 20 mm. The Kaplan-Meier method with a log-rank test and multivariable Cox proportional hazards analyses were used for assessing survival. The samples were evaluated before and after propensity score matching (PSM) with respect to age, sex, histologic type, and pathological LN status. Of 810 patients who met the eligibility criteria, 567 (70.0%) underwent adjuvant chemotherapy. After PSM, patients with adjuvant chemotherapy had a significantly longer survival than those without (median survival: 64.3 vs. 34.0 months, hazard ratio for death: 0.61, p < 0.0001). Multivariate analyses after PSM showed that younger age (p = 0.0206), female (p = 0.0005), and adjuvant chemotherapy (p < 0.0001) were independent prognostic factors for longer survival. Adjuvant chemotherapy has a prognostic impact in patients with small-sized NSCLC and pathological lymph node metastasis who undergo sublobar resection.

The role of upfront neck dissection in definitive radiotherapy for locally advanced hypopharyngeal squamous cell carcinoma: A single-center retrospective analysis.

Hypopharyngeal cancer, constituting 3%-5% of head and neck cancers, predominantly presents as squamous cell carcinoma, with a 5-year overall survival rate of approximately 40%. Treatment modalities for locally advanced cases include chemoradiotherapy; however, the role of upfront neck dissection (UND) remains controversial. This study aimed to investigate the effect of UND on definitive radiotherapy in locally advanced hypopharyngeal carcinoma. This retrospective analysis included consecutive patients with locally advanced hypopharyngeal squamous cell carcinoma who were treated in our department between January 2007 and June 2023. All patients underwent definitive radiotherapy (dRT) at a total dose of 70 Gy in 35 fractions. The patients were categorized into two groups: dRT (radiotherapy with or without chemotherapy) and UND-dRT (surgical neck dissection followed by radiotherapy). Univariate Cox models and multivariate analyses were conducted to investigate the independent prognostic factors for overall survival and locoregional control rate. This study included 115 patients, predominantly male (109/115), with a median age of 66 years. Clinical stage and chemotherapy distribution differed significantly between the dRT and UND-dRT groups. The 3-year overall survival and locoregional control rates for all patients were 63.8% and was 63.3%, respectively. The UND-dRT group exhibited a trend toward improved locoregional control, although this difference was not statistically significant. The multivariate analysis revealed that UND was an independent factor significantly associated with improved overall survival and locoregional control. This study provided evidence supporting the effectiveness of UND in conjunction with definitive radiotherapy for locally advanced hypopharyngeal carcinoma. Future research should focus on validating and refining these findings through well-designed prospective multicenter trials.

Predictive and prognostic value of aurora kinase A combined with tumor-infiltrating lymphocytes in medullary thyroid carcinoma.

Aurora kinase A (AURKA) and tumor-infiltrating lymphocytes (TILs) are both known to play an essential role in tumorigenesis. However, the expression and prognostic value of the AURKA and TILs in medullary thyroid carcinoma (MTC) have not yet been investigated. Surgical specimens and clinical data of 137 patients diagnosed with MTC were collected. AURKA expression and TILs infiltration were quantified by immunohistochemistry and hematoxylin-eosin staining. Subsequently, the prognostic value of AURKA expression and TIL infiltration in MTC was evaluated. AURKA was highly expressed in patients with multifocal tumor, cervical lymph node metastasis, and an advanced TNM stage, indicating a high probability of recurrence. AURKA further exhibited a positive correlation with TILs (R = 0.44, P < 0.001). High expression of AURKA combined with a low numbers of TILs (AURKAhigh/TILslow) was identified as an independent prognostic factor for biochemical recurrence (odds ratio: 4.57, 95% confidence interval: 1.54-14.66, P < 0.01) and recurrence-free survival (hazard ratio: 3.64, 95% confidence interval: 1.52-8.71, P < 0.001). The combination of AURKA and TILs apparently improves the prognostic value for biochemical recurrence (area under the curve: 0.751) and structural recurrence (area under the curve: 0.836) of MTC. Notably, AURKAhigh/TILslow demonstrated a high value for prediction of distant or unresectable locoregional recurrence, with an overall accuracy of 86.9%. AURKAhigh is associated with the MTC malignancy. The combination of AURKAhigh/TILslow was identified as novel independent prognostic marker in MTC, predicting incurable disease recurrence with high accuracy.

A novel liver-function-indicators-based prognosis signature for patients with hepatocellular carcinoma treated with anti-programmed cell death-1 therapy

BackgroundThe liver function reserve has a significant impact on the therapeutic effects of anti-programmed cell death-1 (PD-1) for hepatocellular carcinoma (HCC). This study aimed to comprehensively evaluate the ability of liver-function-based indicators to predict prognosis and construct a novel prognostic score for HCC patients with anti-PD-1 immunotherapy.MethodsBetween July 2018 and January 2020, patients diagnosed with HCC who received anti-PD-1 treatment were screened for inclusion in the study. The valuable prognostic liver-function-based indicators were selected using Cox proportional hazards regression analysis to build a novel liver-function-indicators-based signature (LFIS). Concordance index (C-index), the area under the receiver operating characteristic (ROC) curve (AUC), and Kaplan–Meier survival curves were utilized to access the predictive performance of LFIS.ResultsA total of 434 HCC patients who received anti-PD-1 treatment were included in the study. The LFIS, based on alkaline phosphatase-to-albumin ratio index, Child–Pugh score, platelet-albumin score, aspartate aminotransferase-to-lymphocyte ratio index, and gamma-glutamyl transpeptidase-to-lymphocyte ratio index, was constructed and identified as an independent risk factor for patient survival. The C-index of LFIS for overall survival (OS) was 0.692, which was higher than the other single liver-function-based indicator. The AUC of LFIS at 6-, 12-, 18-, and 24-month were 0.74, 0.714, 0.747, and 0.865 for OS, respectively. Patients in the higher-risk LFIS group were associated with both worse OS and PFS. An online and easy-to-use calculator was further constructed for better application of the LFIS signature.ConclusionThe LFIS score had an excellent prognosis prediction ability superior to every single liver-function-based indicator for anti-PD-1 treatment in HCC patients. It is a reliable, easy-to-use tool to stratify risk for OS and PFS in HCC patients who received anti-PD-1 treatment.

Predictive value of positive lymph node ratio in patients with locally advanced gastric remnant cancer.

e16119 Background: Traditional lymph node stage (N stage) has limitations in advanced gastric remnant cancer (GRC)patients; therefore, establishing a new predictive stage is necessary.To explore the predictive value of positive lymph node ratio (LNR) according to clinicopathological characteristics and prognosis of locally advanced GRC. Methods: Seventy-four patients who underwent radical gastrectomy and lymphadenectomy for locally advanced GRC were retrospectively reviewed. The relationship between LNR and clinicopathological characteristics was analyzed. The survival analysis was performed using Kaplan–Meier survival curves and Cox regression model. Results: Number of metastatic LNs, tumor diameter, depth of tumor invasion, Borrmann type, serum tumor biomarkers, and tumor–node–metastasis (TNM) stage were correlated with LNR stage and N stage. Univariate analysis revealed that the factors affecting survival included tumor diameter, anemia, serum tumor biomarkers, vascular or neural invasion, combined resection, LNR stage, N stage, and TNM stage (all P &lt; 0.05). The median survival time for those with LNR0, LNR1, LNR2 and LNR3 stage were 61, 31, 23 and 17 mo, respectively, and the differences were significant ( P = 0.000). Anemia, tumor biomarkers and LNR stage were independent prognostic factors for survival in multivariable analysis (all P &lt; 0.05). Conclusions: The new LNR stage is uniquely based on number of metastatic LNs, with significant prognostic value for locally advanced GRC, and could better differentiate overall survival, compared with N stage.

Assessment of AURKA expression and prognosis prediction in lung adenocarcinoma using machine learning-based pathomics signature

ObjectiveThis study aimed to develop quantitative feature-based models from histopathological images to assess aurora kinase A (AURKA) expression and predict the prognosis of patients with lung adenocarcinoma (LUAD). MethodsA dataset of patients with LUAD was derived from the cancer genome atlas (TCGA) with information on clinical characteristics, RNA sequencing and histopathological images. The TCGA-LUAD cohort was randomly divided into training (n = 229) and testing (n = 98) sets. We extracted quantitative image features from histopathological slides of patients with LUAD using computational approaches, constructed a predictive model for AURKA expression in the training set, and estimated their predictive performance in the test set. A Cox proportional hazards model was used to assess whether the pathomic scores (PS) generated by the model independently predicted LUAD survival. ResultsHigh AURKA expression was an independent risk factor for overall survival (OS) in patients with LUAD (hazard ratio = 1.816, 95 % confidence intervals = 1.257–2.623, P = 0.001). The model based on histopathological image features had significant predictive value for AURKA expression: the area under the curve of the receiver operating characteristic curve in the training set and validation set was 0.809 and 0.739, respectively. Decision curve analysis showed that the model had clinical utility. Patients with high PS and low PS had different survival rates (P = 0.019). Multivariate analysis suggested that PS was an independent prognostic factor for LUAD (hazard ratio = 1.615, 95 % confidence intervals = 1.071–2.438, P = 0.022). ConclusionPathomics models based on machine learning can accurately predict AURKA expression and the PS generated by the model can predict LUAD prognosis.

Development and comprehensive validation of a predictive prognosis model for very early HCC recurrence within one year after curative resection: a multicenter cohort study.

The high incidence of early recurrence after liver resection for hepatocellular carcinoma (HCC) is the main obstacle in achieving good long-term survival outcomes. The aim of the present study is to develop a prognostic model in predicting the risk of very early (1-year) recurrence. Consecutive patients who underwent liver resection for HCC with curative intent at multi-centers in China were enrolled in this study. The VERM-pre (the Preoperative Very Early Recurrence Model of HCC) with good performance was derived and validated by internal and external cohorts retrospectively and by another two-center cohort prospectively. 7401 patients were enrolled and divided randomly into 3 cohorts. Eight variables (tumor diameter, tumor number, macrovascular invasion, satellite nodule, alpha-fetoprotein, level of HBV-DNA, γ-GT and prothrombin time) were identified as independent risk factors for recurrence-free survival on uni- and multi-variate analyses. The VERM-pre model was developed which showed a high capacity of discrimination (C-index: 0.722; AUROC at 1 year: 0.722)) and was validated comprehensively by the internal, external and prospective cohorts, retrospectively. Calibration plots showed satisfactory fitting of probability of early HCC recurrence in the cohorts. Three risk strata were derived to have significantly different recurrence free survival rates (low-risk: 80.4%-85.4%; intermediate-risk: 59.7%-64.8%; high-risk: 32.6%-42.6%). In the prospective validation cohort, the swimming plot illustrated consistent outcomes with the beginning predictive score. The VERM-pre model accurately predicted the 1-year recurrence rates of HCC after liver resection with curative intent. The model was retrospectively and prospectively validated and then developed as the online tool.

Practical Nomograms and Risk Stratification System for Predicting the Overall and Cancer-specific Survival in Patients with Anaplastic Astrocytoma

ObjectiveAnaplastic astrocytoma (AA) is an uncommon primary brain tumor with highly variable clinical outcomes. Our study aimed to develop practical tools for clinical decision-making in a population-based cohort study. MethodsData from 2997 patients diagnosed with AA between 2004 and 2015 were retrospectively extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The LASSO and multivariate Cox regression analyses were applied to select factors and establish prognostic nomograms. The discriminatory ability of these nomogram models was evaluated using the concordance index (C-index) and receiver operating characteristic curve (ROC). Risk stratifications were established based on the nomograms. ResultsSelected 2997 AA patients were distributed into the training cohort (70%, 2097) and the validation cohort (30%, 900). Age, household income, tumor site, extension, surgery, radiotherapy, and chemotherapy were identified as independent prognostic factors for both overall survival (OS) and cancer-specific survival (CSS). In the training cohort, our nomograms for OS and CSS exhibited good predictive accuracy with C-index values of 0.752 (95% CI: 0.741–0.764) and 0.753 (95% CI: 0.741–0.765), respectively. Calibration and DCA curves showed that the nomograms demonstrated considerable consistency and satisfactory clinical utilities. With the establishment of nomograms, we stratified AA patients into high- and low-risk groups, and constructed risk stratification systems for OS and CSS. ConclusionsWe constructed two predictive nomograms and risk classification systems to effectively predict the OS and CSS rates in AA patients. These models were internally validated with considerable accuracy and reliability and might be helpful in future clinical practices.

Cardiac substructure radiation dose study of conventional radiotherapy for stage N2-3 non-small cell lung cancer.

e20071 Background: There has been widespread reporting on predictive dose parameters for cardiac substructures in radiotherapy for non-small cell lung cancer (NSCLC). However, most advanced NSCLC patients are staged as N2-3, and there is a lack of research on the dose distribution, dose contribution and prognosis of the heart in conventional radiotherapy for N2-3 stage NSCLC. Methods: Retrospective analysis of 274 patients of stage N2-3 NSCLC treated with radiotherapy (RT) of prescription dose from 60Gy to 70Gy. Experienced radiation oncologists delineated the cardiac substructures. All patients were categorized according to different lymph node irradiation and tumor spatial locations. Spearman and linear regression were used for variation of dose-volume parameters, as well as the impact of different primary tumor locations and irradiated lymph nodes on the parameters of the entire heart and substructures. Receiver operating characteristic (ROC) curves, Kaplan-Meier, and Cox regression were performed on the influencing factors of adverse cardiac events after radiotherapy and prognosis analysis. Results: There are significant differences in the dose-volume parameters of the whole heart and its substructures. Mean heart doses (MHD),and the mean doses (Dmean) for the left atrium, right atrium, right ventricle, left ventricle and the left anterior descending coronary artery (LAD) were 15.7Gy (range 0.2-30.0Gy), 19.7Gy (range 0.3-55.0Gy), 9.7Gy (range 0.3-59.8Gy), 7.9Gy (range 0.1-48.2Gy), 6.4Gy (range 0.1-52.6Gy) and 5.2Gy (range 0.1-45.0Gy), respectively. The left atrium Dmean has the most significant impact on MHD compared to other substructures (B = 0.418, P &lt; 0.05). Dose-volume parameters of the whole heart and the left atrium were positively correlated with the irradiation of the 7th lymph node region (P &lt; 0.05). MHD and left atrium Dmean for tumors located in the lower region were significantly higher than those in the upper region (P &lt; 0.001). Patients with LAD V30 ≥ 26.9% had a significantly higher risk of mortality compared to those with LAD V30 &lt; 26.9% (P = 0.003, HR = 2.883, 95% CI = 1.436-5.788). Conclusions: With the dose distribution differences among the whole heart and its substructures. We observed the base of the heart received the highest dose, the dose to the left atrium is particularly required attention. The irradiation of different lymph nodes and different primary lesions has an impact on the dose variations of different cardiac structures. LAD V30 is an independent influencing factor of overall survival (OS) for N2-3 stage NSCLC. This study provides considerable information for the dose optimization of cardiac substructure in radiotherapy planning for N2-3 stage NSCLC.

Retrospective study of BRAF inhibitor-based therapy in patients with BRAF mutated advanced solid tumors (RBAST study).

e23265 Background: BRAF mutations are frequently found in melanoma, non-small cell lung cancer (NSCLC), thyroid cancer, to a lesser degree in other tumor types. These mutations constantly activate the kinase domain and result in MAPK pathway hyperactivation. Successful inhibition of this pathway with BRAF/MEK inhibitors (BRAFi/MEKi) results in a clinically meaningful benefit for some patients. The RBAST study, to assess the efficacy and survival outcomes of BRAF inhibitor-based therapy were investigated in patients with solid tumors harboring BRAF mutations. Methods: Data was collected on a total of 697 cases of solid tumor throughout China between Sep 2018 and Dec 2023. Next Generation Sequencing (NGS) is based on the sequencing of tissue samples. Among the samples, the primary endpoints of this study were objective response rate (ORR), disease control rate (DCR), progress-free survival (PFS) and overall survival (OS). The impact of co-mutations with other genes and BRAF variant allele frequency on treatment efficacy was also assessed in this study. Results: BRAF mutations were detected in 36 cases and 15 patients received BRAFi based therapy were identified. For patients who received BRAFi therapy, the best ORR was 26.7% with 4 patients recorded partial response (PR). There were 2 patients with progressive disease giving a DCR of 86.7%. Responses were observed in 4 types of tumors. PR was observed in patients with colorectal cancer (CRC) and melanoma. Median PFS (mPFS) and median OS (mOS) of these patients were 6.0 months (95% CI: 2.3-7.0) and 17.1 months (95% CI: 4.4-NA), respectively. The co-occurring mutation rates of TP53, PTEN, FAT2 and NF1 were 40% (6/15), 20% (3/15), 20% (3/15) and 13.3% (2/15), respectively. No significant difference (p&gt;0.05) in PFS and OS was observed in any co-occurrence of mutations. BRAF mutation variant allele frequency is not an independent prognostic factor for survival with patients received BRAF inhibitor treatment (p&gt;0.05). Conclusions: To the best of our knowledge, this is the first retrospective study exploring BRAFi treatment effectiveness to BRAF mutated solid tumors for Chinese patients. Treatment with BRAF inhibitors is effective for BRAF mutated advanced solid tumors with DCR of 86.7%, mPFS of 6.0 months and mOS of 17.1 months. Co-mutations with other genes and BRAF variant allele frequency did not impact survival outcomes.

Waiting list mortality and 5-year transplant survival benefit of patients with MASLD: an Italian liver transplant registry study.

BackgroundInternational consensus has recently introduced a new definition of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). We sought to analyse epidemiological trends, prognostic features, and transplant survival benefits of MASLD and non-MASLD patients waiting for liver transplantation (LT) in Italy. Materials and methodsUtilising the Italian Liver Transplant Registry database, we analysed data from adult patients listed for primary LT due to end-stage chronic liver disease between January 2012 and December 2022. Independent multivariable waiting lists and post-transplant survival models were developed for patients with and without hepatocellular carcinoma (HCC). A Monte Carlo simulation was employed to create 5-year transplant benefit distributions based on the presence of MASLD, HCC, and MELD-sodium values. ResultsA total sample of 1,941 MASLD and 11,201 non-MASLD was considered. A significant increase in the prevalence of MASLD as an indication for liver transplantation was observed from 2012 to 2022, both for HCC (from 17.7 to 30%) and non-HCC (from 9.5 to 11.8%) cohorts. Projections suggest that, as early as next year, MASLD will overcome HCV as the second most common indication for transplantation after alcoholic liver disease in Italy. According to univariate and multivariate analyses, MASLD was not an independent predictive factor for patient survival after transplantation. However, it increased the risk of death for patients on the waiting list without HCC (hazard ratio 1.62, p <0.001). At the same MELD-sodium, the 5-year transplant benefit was higher in patients with non-HCC MASLD, followed by patients with HCC, while it was lower in non-HCC patients without MASLD. ConclusionsNon-HCC MASLD patients had an increased waitlist mortality and 5-year transplant survival benefit compared to other candidates.

Perioperative outcomes and survival after neoadjuvant immunochemotherapy for locally advanced esophageal squamous cell carcinoma

ObjectiveThis study aimed to compare the difference in perioperative outcomes and prognosis between neoadjuvant immunochemotherapy and neoadjuvant chemoradiotherapy for locally advanced esophageal squamous cell carcinoma. MethodsThe patients with locally advanced esophageal squamous cell carcinoma receiving neoadjuvant immunochemotherapy or neoadjuvant chemoradiotherapy were identified from a prospectively maintained database at Zhongshan Hospital of Fudan University between January 2018 and March 2022. Propensity score matching was performed to balance the 2 groups. ResultsA total of 124 patient pairs were enrolled in the final analysis. The complete pathological response rate (20.2% vs 29.0%, P = .140) was similar in the 2 groups, whereas the lower major pathological response rate (44.4% vs 61.3%, P = .011) was observed in the neoadjuvant immunochemotherapy group. Neoadjuvant immunochemotherapy was associated with a lower rate of adverse events (42.7% vs 55.6%, P = .047) without additional postoperative complications (38.7% vs 35.5%, P = .693). The neoadjuvant immunochemotherapy group had lower distant metastasis (6.5% vs 16.1%, P = .027) and overall recurrence (11.3% vs 23.4%, P = .019) in the postoperative 1 year. Also, neoadjuvant immunochemotherapy was associated with better progression-free survival (hazard ratio, 0.50; 95% CI, 0.32-0.77; P = .002). Cox proportional hazard analysis showed that neoadjuvant immunochemotherapy (univariable: hazard ratio, 0.55; 95% CI, 0.37-0.82; P = .003; multivariable: hazard ratio, 0.44; 95% CI, 0.29-0.65; P < .001) was one of the independent prognostic factors for progression-free survival. The 2 groups had similar overall survival (hazard ratio, 0.62; 95% CI, 0.36-1.09; P = .094) at the latest follow-up. ConclusionsThis retrospective study showed that neoadjuvant immunochemotherapy was safe and effective for patients with locally advanced esophageal squamous cell carcinoma. Further verification is needed in randomized controlled trials.

CT-based radiomics predicts CD38 expression and indirectly reflects clinical prognosis in epithelial ovarian cancer

BackgroundCluster of differentiation 38 (CD38) has been found to be highly expressed in various solid tumours, and its expression level may be associated with patient prognosis and survival. This study aimed to evaluate the prognostic value of CD38 expression for patients with epithelial ovarian cancer (EOC) and construct two computed tomography (CT)-based radiomics models for predicting CD38 expression. MethodsA total of 333 cases of EOC were enrolled from The Cancer Genome Atlas (TCGA) database for CD38-related bioinformatics and survival analysis. A total of 56 intersection cases from TCGA and The Cancer Imaging Archive (TCIA) databases were selected for radiomics feature extraction and model construction. Logistic regression (LR) and support vector machine (SVM) models were constructed and internally validated using 5-fold cross-validation to assess the performance of the models for CD38 expression levels. ResultsHigh CD38 expression was an independent protective factor (HR = 0.540) for overall survival (OS) in EOC patients. Five radiomics features based on CT images were selected to build models for the prediction of CD38 expression. In the training and internal validation sets, for the receiver operating characteristic (ROC) curve, the LR model reached an area under the curve (AUC) of 0.739 and 0.732, while the SVM model achieved AUC values of 0.741 and 0.700, respectively. For the precision-recall (PR) curve, the LR and SVM models demonstrated an AUC of 0.760 and 0.721. The calibration curves and decision curve analysis (DCA) provided evidence supporting the fitness and net benefit of the models. ConclusionsHigh levels of CD38 expression can improve OS in EOC patients. CT-based radiomics models can be a new predictive tool for CD38 expression, offering possibilities for individualised survival assessment for patients with EOC.

Prognostic significance of the aspartate aminotransferase to lymphocyte ratio index in patients with acute myocardial infarction.

This study aimed to investigate the clinical value and prognostic significance of the alanine aspartate aminotransferase-to-lymphocyte ratio index (ALRI) in patients diagnosed with acute myocardial infarction (AMI). Clinical indices of patients with AMI were collected from the Medical Information Mark for Intensive Care (MIMIC) III database and Wuhan Sixth Hospital. Cox regression analysis was used to explore whether ALRI was a risk factor for a worse prognosis in patients with AMI, and a nomogram including ALRI was created to estimate its predictive performance for 28-day mortality. Based on clinical data from the MIMIC-III database, we found that a high ALRI was closely associated with a variety of clinical parameters. It was an important risk factor for 28-day survival in patients with AMI (HR = 5.816). ALRI had a high predictive power for worse 28-day survival in patients with AMI(area under the curve [AUC] = 0.754). Additionally, we used clinical data from the Wuhan Sixth Hospital to verify the predictive power of ALRI in patients with AMI, and a high level of ALRI remained an independent risk factor for worse survival in patients with AMI (HR = 4.969). The AMI nomogram, including ALRI, displayed a good predictive performance for 28-day mortality in both the MIMIC-III (AUC = 0.826) and Wuhan Sixth Hospital cohorts (AUC = 0.795). The ALRI is closely related to the survival outcomes of patients with newly diagnosed AMI, indicating that it could serve as a novel biomarker for risk stratification such patients.