R2-ISS staging combined with circulating plasma cells improves risk stratification for newly diagnosed multiple myeloma: a single-center real-world study.

We aimed to evaluate if circulating plasma cells (CPC) detected by flow cytometry could add prognostic value of R2-ISS staging. We collected the electronic medical records of 336 newly diagnosed MM patients (NDMM) in our hospital from January 2017 to June 2023. The median overall survival (OS) for patients and R2-ISS stage I-IV were not reached (NR), NR, 58 months and 53 months, respectively. There was no significant difference in OS between patients with stage I and patients with stage II (P = 0.309) or between patients with stage III and patients with stage IV (P = 0.391). All the cases were re-classified according to R2-ISS stage and CPC numbers ≥ 0.05% (CPC high) or<0.05% (CPC low) into four new risk groups: Group 1: R2-ISS stage I + R2-ISS stage II and CPC low, Group 2: R2-ISS stage II and CPC high + R2-ISS stage III and CPC low, Group 3: R2-ISS stage III and CPC high + R2-ISS stage IV and CPC low, Group 4: R2-ISS stage IV and CPC high. The median OS were NR, NR, 57 months and 32 months. OS of Group 1 was significantly longer than that of Group 2 (P = 0.033). OS in Group 2 was significantly longer than that of Group 3 (P = 0.007). OS in Group 3 was significantly longer than that of Group 4 (P = 0.041). R2-ISS staging combined with CPC can improve risk stratification for NDMM patients.

Clinical features and treatment outcomes of intraocular and ocular adnexal metastasis.

The aim of this study was to investigate the primary sites, clinical characteristics, and treatment outcomes of patients with metastatic tumors in the eye and ocular adnexa. This retrospective case series consisted of 42 patients diagnosed with intraocular metastasis (IM) or ocular adnexal metastasis (OAM) at a tertiary center between January 2001 and June 2023. The patients comprised 18 men and 24 women; 24 (57%) and 18 (43%) patients were diagnosed with IM and OAM, respectively. In the IM group, the primary tumors originated from the lungs (79%), followed by the breasts (17%). In the OAM group, the primary tumors originated from the breasts (33%). Previously, 57% of the patients had been diagnosed with cancer. In the IM group, 38% exhibited bilateral involvement. Only 6% of the patients with OAM had bilateral diseases. The 1-, 3-, and 5-year overall survival (OS) was 42%, 18%, and 7%, respectively. The median OS since metastasis diagnosis in the lungs and breast was 11.8 and 10.5 months, respectively. Lung cancer remains the predominant primary cancer in IM, whereas breast cancer is the major cancer in OAM. Despite poor OS, early detection will facilitate the prompt treatment of primary cancer and metastatic sites.

A clinical tool to predict overall survival of elderly patients with soft tissue sarcoma after surgical resection.

With the aging world population, the incidence of soft tissue sarcoma (STS) in the elderly gradually increases and the prognosis is poor. The primary goal of this research was to analyze the relevant risk factors affecting the postoperative overall survival in elderly STS patients and to provide some guidance and assistance in clinical treatment. The study included 2,353 elderly STS patients from the Surveillance, Epidemiology, and End Results database. To find independent predictive variables, we employed the Cox proportional risk regression model. R software was used to develop and validate the nomogram model to predict postoperative overall survival. The performance and practical value of the nomogram were evaluated using calibration curves, the area under the curve, and decision curve analysis. Age, tumor primary site, disease stage, tumor size, tumor grade, N stage, and marital status, are the risk variables of postoperative overall survival, and the prognostic model was constructed on this basis. In the two sets, both calibration curves and receiver operating characteristic curves showed that the nomogram had high predictive accuracy and discriminative power, while decision curve analysis demonstrated that the model had good clinical usefulness. A predictive nomogram was designed and tested to evaluate postoperative overall survival in elderly STS patients. The nomogram allows clinical practitioners to more accurately evaluate the prognosis of individual patients, facilitates the progress of individualized treatment, and provides clinical guidance.

Metabolism score and machine learning models for the prediction of esophageal squamous cell carcinoma progression.

The incomplete prediction of prognosis in esophageal squamous cell carcinoma (ESCC) patients is attributed to various therapeutic interventions and complex prognostic factors. Consequently, there is a pressing demand for enhanced predictive biomarkers that can facilitate clinical management and treatment decisions. This study recruited 491 ESCC patients who underwent surgical treatment at Huashan Hospital, Fudan University. We incorporated 14 blood metabolic indicators and identified independent prognostic indicators for overall survival through univariate and multivariate analyses. Subsequently, a metabolism score formula was established based on the biochemical markers. We constructed a nomogram and machine learning models utilizing the metabolism score and clinically significant prognostic features, followed by an evaluation of their predictive accuracy and performance. We identified alkaline phosphatase, free fatty acids, homocysteine, lactate dehydrogenase, and triglycerides as independent prognostic indicators for ESCC. Subsequently, based on these five indicators, we established a metabolism score that serves as an independent prognostic factor in ESCC patients. By utilizing this metabolism score in conjunction with clinical features, a nomogram can precisely predict the prognosis of ESCC patients, achieving an area under the curve (AUC) of 0.89. The random forest (RF) model showed superior predictive ability (AUC = 0.90, accuracy = 86%, Matthews correlation coefficient = 0.55). Finally, we used an RF model with optimal performance to establish an online predictive tool. The metabolism score developed in this study serves as an independent prognostic indicator for ESCC patients.

Efficacy and safety of androgen receptor inhibitors for treatment of advanced prostate cancer: A systematic review and network meta-analysis.

AIMS: Androgen receptor inhibitors (ARIs) have become an effective treatment for advanced prostate cancer (PC). However, it is unknown which ARI is the most helpful and safe for men with advanced PC. Our aim is to help physicians make clinical decisions and provide medication guidelines for patients with advanced PC to avoid potential risks when using ARIs for treatment. METHODS: We systematically searched the following databases: PubMed, Embase and Cochrane Library, with a literature publication deadline of February 2023. The primary efficacy outcomes were 18-month overall survival (OS), treatment-emergent adverse events (TEAEs), hypertension and fatigue. The network meta-analysis (NMA) was performed by Stata 15.1, and Revman 5.3 was used to assess the included studies' risk of bias. RESULTS: The analysis included 26 trials with 26 263 people. The surface under the cumulative ranking curve (SUCRA) concluded that enzalutamide (86.8%) showed the best effect in prolonging the OS of patients. Flutamide led to the highest risk of TEAEs (29.9%) and AEs leading to discontinuation (12.8%). Apalutamide (13.4%) led to the highest risk of grade ≥3 TEAEs. Enzalutamide had the highest risk of hypertension (0.2%), grade ≥3 hypertension (4.5%) and fatigue (5.2%). CONCLUSIONS: This NMA indicates there is no one ARI to reach both the most effective and safe therapy aims for treating advanced PC and that there is a compromise between the efficacy and safety of ARIs in the treatment of advanced PC. Physicians should weigh the risks to safety against the anticipated benefits when prescribing these drugs to patients with PC.

The role of biomarkers and dosimetry parameters in overall and progression free survival prediction for patients treated with personalized 90Y glass microspheres SIRT: a preliminary machine learning study.

BACKGROUND: Overall Survival (OS) and Progression-Free Survival (PFS) analyses are crucial metrics for evaluating the efficacy and impact of treatment. This study evaluated the role of clinical biomarkers and dosimetry parameters on survival outcomes of patients undergoing 90Y selective internal radiation therapy (SIRT). MATERIALS/METHODS: This preliminary and retrospective analysis included 17 patients with hepatocellular carcinoma (HCC) treated with 90Y SIRT. The patients underwent personalized treatment planning and voxel-wise dosimetry. After the procedure, the OS and PFS were evaluated. Three structures were delineated including tumoral liver (TL), normal perfused liver (NPL), and whole normal liver (WNL). 289 dose-volume constraints (DVCs) were extracted from dose-volume histograms of physical and biological effective dose (BED) maps calculated on 99mTc-MAA and 90Y SPECT/CT images. Subsequently, the DVCs and 16 clinical biomarkers were used as features for univariate and multivariate analysis. Cox proportional hazard ratio (HR) was employed for univariate analysis. HR and the concordance index (C-Index) were calculated for each feature. Using eight different strategies, a cross-combination of various models and feature selection (FS) methods was applied for multivariate analysis. The performance of each model was assessed using an averaged C-Index on a three-fold nested cross-validation framework. The Kaplan-Meier (KM) curve was employed for univariate and machine learning (ML) model performance assessment. RESULTS: The median OS was 11 months [95% CI: 8.5, 13.09], whereas the PFS was seven months [95% CI: 5.6, 10.98]. Univariate analysis demonstrated the presence of Ascites (HR: 9.2[1.8,47]) and the aim of SIRT (segmentectomy, lobectomy, palliative) (HR: 0.066 [0.0057, 0.78]), Aspartate aminotransferase (AST) level (HR:0.1 [0.012-0.86]), and MAA-Dose-V205(%)-TL (HR:8.5[1,72]) as predictors for OS. 90Y-derived parameters were associated with PFS but not with OS. MAA-Dose-V205(%)-WNL, MAA-BED-V400(%)-WNL with (HR:13 [1.5-120]) and 90Y-Dose-mean-TL, 90Y-D50-TL-Gy, 90Y-Dose-V205(%)-TL, 90Y-Dose- D50-TL-Gy, and 90Y-BED-V400(%)-TL (HR:15 [1.8-120]) were highly associated with PFS among dosimetry parameters. The highest C-index observed in multivariate analysis using ML was 0.94 ± 0.13 obtained from Variable Hunting-variable-importance (VH.VIMP) FS and Cox Proportional Hazard model predicting OS, using clinical features. However, the combination of VH. VIMP FS method with a Generalized Linear Model Network model predicting OS using Therapy strategy features outperformed the other models in terms of both C-index and stratification of KM curves (C-Index: 0.93 ± 0.14 and log-rank p-value of 0.023 for KM curve stratification). CONCLUSION: This preliminary study confirmed the role played by baseline clinical biomarkers and dosimetry parameters in predicting the treatment outcome, paving the way for the establishment of a dose-effect relationship. In addition, the feasibility of using ML along with these features was demonstrated as a helpful tool in the clinical management of patients, both prior to and following 90Y-SIRT.

The Negative Impact of Sarcopenia on Hepatocellular Carcinoma Treatment Outcomes.

INTRODUCTION: Hepatocellular carcinoma (HCC) represents a major global health concern, characterized by evolving etiological patterns and a range of treatment options. Among various prognostic factors, sarcopenia, characterized by loss of skeletal muscle mass, strength, and function, has emerged as a pivotal contributor to HCC outcomes. Focusing on liver transplantation, surgical resection, locoregional treatments, and systemic therapies, this review aims to analyze the impact of sarcopenia on HCC treatment outcomes, shedding light on an underexplored subject in the pursuit of more personalized management. METHODS: A comprehensive literature review was conducted by searching peer-reviewed articles on sarcopenia and treatment outcomes in patients with HCC from inception up to October 2023. RESULTS: Sarcopenia was found to be prevalent among HCC patients, exhibiting different occurrence, possibly attributable to diverse diagnostic criteria. Notably, despite variations in studies utilizing skeletal muscle indices, sarcopenia independently correlated with lower overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS) across surgical (both transplantation and resection), locoregional, and systemic therapies, including tyrosine-kinase inhibitors (TKIs) and immune-checkpoint inhibitors (ICIs). Moreover, a link between sarcopenia and increased rate and severity of adverse events, particularly in surgery and TKIs recipients, and larger tumor size at diagnosis was observed. While baseline sarcopenia negatively influenced treatment outcomes, alterations in muscle mass post-treatment emerged as primary determinants of reduced OS. CONCLUSIONS: Sarcopenia, either present before or after HCC treatment, negatively correlates with response to it, across all etiologies and therapeutic strategies. Although only a few studies have evaluated the impact of supervised physical activity training on muscle mass and OS after HCC treatment, it is crucial to evaluate the presence of sarcopenia before treatment initiation, to better stratify patients' prognosis, thus performing a more tailored approach, and identify therapies able to restore muscle mass in HCC patients. Conversely, the impact of sarcopenia on HCC recurrence and extrahepatic spread remains inadequately explored.

A Head-to-Head Comparison of the First-Line Treatments for Locally Advanced or Metastatic Urothelial Cancer: Is There Still a Role for Chemotherapy?

BACKGROUND: Patients with locally advanced/metastatic urothelial cancer have been conventionally treated with platinum-based chemotherapy. Recently, numerous new treatments have been proposed to improve overall survival (OS) and reduce adverse effects, but no direct head-to-head comparisons among these agents are available. METHODS: The treatments evaluated in our analyses included (a) monotherapy with immune checkpoint inhibitors (ICI); (b) combinations of an ICI with chemotherapy; and (c) combinations of an ICI with other drugs. Using OS as the endpoint, a series of indirect comparisons were performed to rank the most effective regimens against both chemotherapy and each other. Our analysis was based on the application of an artificial intelligence software program (IPDfromKM method) that reconstructs individual patient data from the information reported in the graphs of Kaplan-Meier curves. RESULTS: A total of five studies published in six articles were included. In our main analysis, nivolumab plus chemotherapy showed better OS compared to chemotherapy (HR = 0.70, 95% CI: 0.59-0.82), while durvalumab plus tremelimumab showed no OS benefit (HR = 0.95, 95% CI 0.82-1.11). More interestingly, enfortumab vedotin plus pembrolizumab significantly prolonged OS compared to both chemotherapy alone (HR = 0.53, 95% CI 0.45-0.63) and nivolumab plus chemotherapy (HR = 0.76, 95% CI 0.60-0.97). DISCUSSION AND CONCLUSION: Among new treatments for locally advanced and metastatic urothelial cancer, enfortumab vedotin plus pembrolizumab showed the best efficacy in terms of OS. Our results support the use of this combination as a first-line treatment in this setting.

Improving Sarcoma Outcomes: Target Trial Emulation to Compare the Impact of Unplanned and Planned Resections on the Outcome.

This study follows the Target Trial Emulation (TTE) framework to assess the impact of unplanned resections (UEs) and planned resections (PEs) of sarcomas on local recurrence-free survival (LRFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS). Sarcomas, malignant tumors with mesenchymal differentiation, present a significant clinical challenge due to their rarity, complexity, and the frequent occurrence of UEs, which complicates effective management. Our analysis utilized real-world-time data from the Swiss Sarcoma Network, encompassing 429 patients, to compare the impact of UEs and PEs, adjusting for known prognostic factors through a multivariable Cox regression model and propensity score weighting. Our findings reveal a significantly higher risk of local recurrence for UEs and a short-term follow-up period that showed no marked differences in MFS, CSS, and OS between the UE and PE groups, underlining the importance of optimal initial surgical management. Furthermore, tumor grade was validated as a critical prognostic factor, influencing outcomes irrespective of surgical strategy. This study illuminates the need for improved referral systems to specialized sarcoma networks to prevent UEs and advocates for the integration of TTE in sarcoma research to enhance clinical guidelines and decision-making in sarcoma care. Future research should focus on the prospective validations of these findings and the exploration of integrated care models to reduce the incidence of UEs and improve patient outcomes.

Unveiling the secrets of gastrointestinal mucous adenocarcinoma survival after surgery with artificial intelligence: A population-based study.

BACKGROUND: Research on gastrointestinal mucosal adenocarcinoma (GMA) is limited and controversial, and there is no reference tool for predicting postoperative survival. AIM: To investigate the prognosis of GMA and develop predictive model. METHODS: From the Surveillance, Epidemiology, and End Results database, we collected clinical information on patients with GMA. After random sampling, the patients were divided into the discovery (70% of the total, for model training), validation (20%, for model evaluation), and completely blind test cohorts (10%, for further model evaluation). The main assessment metric was the area under the receiver operating characteristic curve (AUC). All collected clinical features were used for Cox proportional hazard regression analysis to determine factors influencing GMA's prognosis. RESULTS: This model had an AUC of 0.7433 [95% confidence intervals (95%CI): 0.7424-0.7442] in the discovery cohort, 0.7244 (GMA: 0.7234-0.7254) in the validation cohort, and 0.7388 (95%CI: 0.7378-0.7398) in the test cohort. We packaged it into Windows software for doctors' use and uploaded it. Mucinous gastric adenocarcinoma had the worst prognosis, and these were protective factors of GMA: Regional nodes examined [hazard ratio (HR): 0.98, 95%CI: 0.97-0.98, P < 0.001)] and chemotherapy (HR: 0.62, 95%CI: 0.58-0.66, P < 0.001). CONCLUSION: The deep learning-based tool developed can accurately predict the overall survival of patients with GMA postoperatively. Combining surgery, chemotherapy, and adequate lymph node dissection during surgery can improve patient outcomes.

Predictive value of preoperative routine examination for the prognosis of patients with pT2N0M0 or pT3N0M0 colorectal cancer.

BACKGROUND: In recent years, the incidence of colorectal cancer (CRC) has been increasing. With the popularization of endoscopic technology, a number of early CRC has been diagnosed. However, despite current treatment methods, some patients with early CRC still experience postoperative recurrence and metastasis. AIM: To search for indicators associated with early CRC recurrence and metastasis to identify high-risk populations. METHODS: A total of 513 patients with pT2N0M0 or pT3N0M0 CRC were retrospectively enrolled in this study. Results of blood routine test, liver and kidney function tests and tumor markers were collected before surgery. Patients were followed up through disease-specific database and telephone interviews. Tumor recurrence, metastasis or death were used as the end point of study to find the risk factors and predictive value related to early CRC recurrence and metastasis. RESULTS: We comprehensively compared the predictive value of preoperative blood routine, blood biochemistry and tumor markers for disease-free survival (DFS) and overall survival (OS) of CRC. Cox multivariate analysis demonstrated that low platelet count was significantly associated with poor DFS [hazard ratio (HR) = 0.995, 95% confidence interval (CI): 0.991-0.999, P = 0.015], while serum carcinoembryonic antigen (CEA) level (HR = 1.008, 95%CI: 1.001-1.016, P = 0.027) and serum total cholesterol level (HR = 1.538, 95%CI: 1.026-2.305, P = 0.037) were independent risk factors for OS. The cutoff value of serum CEA level for predicting OS was 2.74 ng/mL. Although the OS of CRC patients with serum CEA higher than the cutoff value was worse than those with lower CEA level, the difference between the two groups was not statistically significant (P = 0.075). CONCLUSION: For patients with T2N0M0 or T3N0M0 CRC, preoperative platelet count was a protective factor for DFS, while serum CEA level was an independent risk factor for OS. Given that these measures are easier to detect and more acceptable to patients, they may have broader applications.

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

BACKGROUND: Gastric signet ring cell carcinoma (GSRC) represents a specific subtype of gastric cancer renowned for its contentious epidemiological features, treatment principles, and prognostic factors. AIM: To investigate the epidemiology of GSRC and establish an improved model for predicting the prognosis of patients with locally advanced GSRC (LAGSRC) after surgery. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Short-term OS as a surrogate endpoint for 5-year OS in nasopharyngeal carcinoma in non-endemic area.

PURPOSE: To address this evidence gap and validate short-term OS at less than 5 years as a reliable surrogate endpoint for 5-year OS. METHODS: We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database, focusing on non-metastatic NPC patients diagnosed between 2010 and 2015. Patients were categorized into radiotherapy and chemoradiotherapy groups. RESULTS: This retrospective study examined 2,047 non-metastatic NPC patients. Among them, 217 received radiotherapy, and 1,830 received chemoradiotherapy. Our analysis results indicated that the 4-year OS may serve as a reliable surrogate endpoint for patients with AJCC clinical stage I (80 vs. 78%, P = 0.250), regardless of the treatment received. Specifically, in the radiotherapy group, patients with stage I, T0-T1, and N0 NPC showed similar OS rates at 4 and 5 years (83 vs. 82%, P = 1.000; 78 vs. 76%, P = 0.250; 78 vs. 77%, P = 0.500, respectively). Similarly, patients with stage II-IV, T2-T4, and N1-3 NPC showed no significant difference in OS rates between 3 and 5 years (57 vs. 51%, P = 0.063; 52 vs. 46%, P = 0.250; 54 vs. 46%, P = 0.125, respectively) in the radiotherapy group. In the chemoradiotherapy group, only the 3-year OS rate did not significantly differ from that at 5 years in stage I patients (79vs. 72%, P = 0.063). CONCLUSIONS: Our study suggests that short-term surrogate endpoints may be valuable for evaluating 5-year OS outcomes in NPC patients in non-endemic areas.

Identification and bioinformatic characterization of a serum miRNA signature for early detection of laryngeal squamous cell carcinoma.

BACKGROUND: The growing understanding of cancer biology and the establishment of new treatment modalities has not yielded the expected results in terms of survival for Laryngeal Squamous Cell Cancer (LSCC). Early diagnosis, as well as prompt identification of patients with high risk of relapse would ensure greater chance of therapeutic success. However, this goal remains a challenge due to the absence of specific biomarkers for this neoplasm. METHODS: Serum samples from 45 LSCC patients and 23 healthy donors were collected for miRNA expression profiling by TaqMan Array analysis. Additional 20 patients and 42 healthy volunteers were included for the validation set, reaching an equal number of clinical samples for each group. The potential diagnostic ability of the such identified three-miRNA signature was confirmed by ROC analysis. Moreover, each miRNA was analyzed for the possible correlation with HNSCC patients' survival and TNM status by online databases Kaplan-Meier (KM) plotter and OncomiR. In silico analysis of common candidate targets and their network relevance to predict shared biological functions was finally performed by PANTHER and GeneMANIA software. RESULTS: We characterized serum miRNA profile of LSCC patients identifying a novel molecular signature, including miR-223, miR-93 and miR-532, as circulating marker endowed with high selectivity and specificity. The oncogenic effect and the prognostic significance of each miRNA was investigated by bioinformatic analysis, denoting significant correlation with OS. To analyse the molecular basis underlying the pro-tumorigenic role of the signature, we focused on the simultaneously regulated gene targets-IL6ST, GTDC1, MAP1B, CPEB3, PRKACB, NFIB, PURB, ATP2B1, ZNF148, PSD3, TBC1D15, PURA, KLF12-found by prediction tools and deepened for their functional role by pathway enrichment analysis. The results showed the involvement of 7 different biological processes, among which inflammation, proliferation, migration, apoptosis and angiogenesis. CONCLUSIONS: In conclusion, we have identified a possible miRNA signature for early LSCC diagnosis and we assumed that miR-93, miR-223 and miR-532 could orchestrate the regulation of multiple cancer-related processes. These findings encourage the possibility to deepen the molecular mechanisms underlying their oncogenic role, for the desirable development of novel therapeutic opportunities based on the use of short single-stranded oligonucleotides acting as non-coding RNA antagonists in cancer.

Exploring the prognostic impact of differences in treatment strategies for SCLC with different histologies and prognostic factors for C-SCLC: A SEER population-based study.

Background: Combined small cell lung cancer (C-SCLC) is a rare type of small cell lung cancer (SCLC), and it is controversial whether to choose the same treatment regimen as SCLC due to its multiple histologic components. Study methods and results: Records of patients with small cell lung cancer diagnosed between 2010 and 2020 were extracted using the SEER database. The OS of patients with different histological types under the same staging and treatment regimen was analyzed. It was found that early-stage (stage IA-IIA) surgical treatment, systemic chemotherapy alone, and chemoradiotherapy were more efficacious than C-SCLC and P-SCLC in patients with limited-stage (P = 0.054, P = 0.001, P = 0.019). In patients with extensive staging, the OS of patients with systemic chemotherapy regimens differed (P = 0.045) and was better in C-SCLC than in P-SCLC. We further explored the treatment strategy for patients with C-SCLC, which was shown by a COX regression model based on prognostic factors screened by Random Forest and LASSO regression models. Surgery, radiotherapy, and chemotherapy would be beneficial for survival. In a subgroup analysis based on stage and treatment regimen, it was shown that patients with early staging (stage IA-IIA) had a better prognosis with surgery (P < 0.001); in patients with extensive staging, chemoradiotherapy was favorable to the patient's prognosis (P = 0.022). Conclusion: Both limited-stage and extensive-stage C-SCLC patients are more sensitive to chemotherapy than P-SCLC patients. Patients with C-SCLC who have access to surgery should undergo surgery as early as possible, while chemoradiotherapy is recommended for patients with extensive staging. Patient age, gender, tumor size, surgery, chemotherapy, radiotherapy, and metastasis may individually affect patient prognosis.

21-Gene Recurrence Score and Survival Outcomes in the Phase III Multicenter TAILORx Clinical Trial.

BACKGROUND: Recurrence score (RS) based on a 21-gene genomic assay is frequently used to estimate risk of distant recurrence for choice of adjuvant chemotherapy in breast cancer. It remains unclear whether RS is an independent prognostic factor for breast cancer-specific survival (BCSS) and overall survival (OS) in the TAILORx trial population. METHODS: We evaluated the association of RS with BCSS and OS plus recurrence-free interval (RFI) and invasive disease-free survival (DFS) using multivariable Cox proportional hazards regression analysis, adjusting for clinicopathologic measures, in 8,916 patients with hormone receptor-positive, HER2-negative, node-negative breast cancer. Likelihood ratio (LR) test was used to assess the relative amount of prognostic information provided by RS to BCSS, OS, RFI, and DFS, comparatively. RESULTS: Event rates for BCSS, OS, RFI, and DFS were 1.7%, 5.2%, 5.6%, and 12.6%, respectively, by up to 11.6 years of follow-up. Compared with low-range RS (0-10), patients with midrange (11-25) and high-range (26-100) RS had inferior BCSS (adjusted hazard ratio [aHR], 5.12 [95% CI, 2.09-16.92] and 8.03 [95% CI, 2.91-28.47], respectively) and RFI (aHR, 1.68 [95% CI, 1.23-2.36] and 3.05 [95% CI, 2.02-4.67], respectively), independent of clinicopathologic factors. High-range score was associated with an increased risk of DFS (aHR, 1.56 [95% CI, 1.20-2.04]) but not significantly associated with OS (aHR, 1.44 [95% CI, 0.95-2.18]). Midrange score was associated with neither DFS (aHR, 1.15 [95% CI, 0.96-1.38]) nor OS (HR 1.14 [95% CI, 0.87-1.52]). LR-χ2 values were 83.0 and 65.1 for RFI and BCSS, respectively, and 17.5 and 33.6 for OS and DFS, respectively (P<.0001). CONCLUSIONS: RS is an independent measure for BCSS and recurrence prognoses relative to OS in early-stage breast cancer. It carries more prognostic information for breast cancer-specific outcomes.

Aligning outcomes: DLBCL prognosis at a 4th Level University Hospital in Bogotá is comparable to high-income nations, identification of additional prognostic markers for overall survival and relapse.

Introduction: Diffuse large B-cell lymphoma (DLBCL), a prevalent non-Hodgkin lymphoma subtype, displays diverse clinical outcomes with persistently high mortality and relapse rates, despite treatment advancements. Notably, the Hispanic demographic lacks consideration in existing prognostic indices for DLBCL. Methods: A retrospective cohort study encompassing 112 DLBCL patients diagnosed between 2010 and 2020 was conducted at our institution. Patient data, including overall survival (OS), treatment response, and relapse, were analysed. Results: With a median age of 65 years and a predominant male population (60.7%), both the International Prognostic Index (IPI) and revised IPI correlated with OS. In multivariate analysis, patients with ki-67 ≥ 60% exhibited higher mortality risk (Hazard Ratio: 2.35, 95% confidence intervals (CI) 1.05-5.27, p = 0.039), even when controlled by IPI category and B2-microglobulin levels. The absence of B symptoms served as a protective factor for relapse (p < 0.01, OR: 0.147, 95% CI 0.058-0.376) when controlling for ki-67, CD5, and IPI. Conclusion: Our cohort demonstrated a 5-year OS rate comparable to high-income countries, highlighting the need for tailored prognostic models for Hispanic DLBCL patients. This study identifies easily accessible parameters aligning with regional resource constraints, providing insights into additional prognostic factors for DLBCL in the Hispanic population.

The Potential Significance of the EMILIN3 Gene in Augmenting the Aggressiveness of Low-Grade Gliomas is Noteworthy.

Purpose: Low-grade gliomas (LGG) are common brain tumors with high mortality rates. Cancer cell invasion is a significant factor in tumor metastasis. Novel biomarkers are urgently needed to predict LGG prognosis effectively. Methods: The data for LGG were obtained from the Bioinformatics database. A consensus clustering analysis was performed to identify molecular subtypes linked with invasion in LGG. Differential expression analysis was performed to identify differentially expressed genes (DEGs) between the identified clusters. Enrichment analyses were then conducted to explore the function for DEGs. Prognostic signatures were placed, and their predictive power was assessed. Furthermore, the invasion-related prognostic signature was validated using the CGGA dataset. Subsequently, clinical specimens were procured in order to validate the expression levels of the distinct genes examined in this research, and to further explore the impact of these genes on the glioma cell line LN229 and HS-683. Results: Two invasion-related molecular subtypes of LGG were identified, and we sifted 163 DEGs between them. The enrichment analyses indicated that DEGs are mainly related to pattern specification process. Subsequently, 10 signature genes (IGF2BP2, SRY, CHI3L1, IGF2BP3, MEOX2, ABCC3, HOXC4, OTP, METTL7B, and EMILIN3) were sifted out to construct a risk model. Besides, the survival (OS) in the high-risk group was lower. The performance of the risk model was verified. Furthermore, a highly reliable nomogram was generated. Cellular experiments revealed the ability to promote cell viability, value-addedness, migratory ability, invasive ability, and colony-forming ability of the glioma cell line LN229 and HS-683. The qRT-PCR analysis of clinical glioma samples showed that these 10 genes were expressed at higher levels in high-grade gliomas than in low-grade gliomas, suggesting that these genes are associated with poor prognosis of gliomas. Conclusion: Our study sifted out ten invasion-related biomarkers of LGG, providing a reference for treatments and prognostic prediction in LGG.

Prognostic factors and outcomes in anti-neutrophil cytoplasmic antibody-associated glomerulonephritis: A retrospective single-center study from southern China.

Objective: To investigate the prognostic factors and outcomes in patients with anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN) in Southern China. Methods: A retrospective analysis of medical records of patients with ANCA-GN admitted to Shenzhen Hospital of Southern Medical University and Nanfang Hospital of Southern Medical University between September 2011 and September 2021 was performed. The clinical presentation, biological, and renal pathology were collected. In addition, the risk factors for end-stage renal disease (ESRD) and short-term overall survival in patients with ANCA-GN were analyzed. Results: A total of 93 patients with ANCA-GN were included in the study. Of them, 91.4%, were perinuclear anti-neutrophil cytoplasmic antibodies (MPO-pANCA)-positive. Approximately one-quarter (24.7%) of patients had progressed to ESRD, and 7.5% died within six months. Most patients presented with hematuria (94.6%), proteinuria (78.5%), elevated serum creatinine (86.0%), anemia (90.3%), and increased erythrocyte sedimentation rate (ESR) (44.1%). The majority (94.6%) of patients presented with crescent formations at histopathological examination. Serum creatinine, hemoglobin, and Birmingham vasculitis activity score (BVAS) were all independent factors for ESRD (P<0.05). Moreover, while ANCA renal risk score (ARRS) has an impact on prognosis of nephropathy, it did not influence ESRD independently (P>0.05). The effect of Berden's histopathologic classification on ESRD has not been confirmed. Age at onset, ESR and cardiovascular involvement were all independent factors affecting short-term overall survival of patients with ANCA-GN (P<0.05). Conclusions: Serum creatinine, hemoglobin, and BVAS were all independent risk factors of ESRD, while ARRS and Berden's histopathologic classification were not. Age at onset, ESR, and cardiovascular involvement were independent risk factors for the overall six-month survival rate in patients with ANCA-GN.

Lenvatinib radiofrequency ablation sequential therapy offers survival benefits for patients with unresectable hepatocellular carcinoma at intermediate stage and the liver reserve of Child-Pugh A category: A multicenter study.

AIM: This study aims to evaluate the efficacy and safety of lenvatinib radiofrequency ablation (RFA) sequential therapy for certain hepatocellular carcinoma (HCC) patients. METHODS: One hundred and nineteen patients with unresectable HCC in the intermediate stage with Child-Pugh A were retrospectively recruited in a multicenter setting. Those in the lenvatinib RFA sequential therapy group received lenvatinib initially, followed by RFA and the retreatment with lenvatinib. The study compared overall survival (OS), progression-free survival (PFS), tumor response, and adverse events (AEs) between patients undergoing sequential therapy and lenvatinib monotherapy. RESULTS: After propensity score matching, 25 patients on sequential therapy and 50 on monotherapy were evaluated. Independent factors influencing OS were identified as sequential therapy, modified albumin-bilirubin (mALBI) grade, and relative dose intensity (%) with hazard ratios (HRs) of 0.381 (95% confidence interval [CI], 0.186-0.782), 2.220 (95% CI, 1.410-3.493), and 0.982 (95% CI, 0.966-0.999), respectively. Stratified analysis based on mALBI grades confirmed the independent influence of treatment strategy across all mALBI grades for OS (HR, 0.376; 95% CI, 0.176-0.804). Furthermore, sequential therapy was identified as an independent factor of PFS (HR, 0.382; 95% CI, 0.215-0.678). Sequential therapy significantly outperformed monotherapy on survival benefits (OS: 38.27 vs. 18.96 months for sequential therapy and monotherapy, respectively, p = 0.004; PFS: 13.80 vs. 5.32 months for sequential therapy and monotherapy, respectively, p < 0.001). Sequential therapy was significantly associated with complete response by modified Response Evaluation Criteria in Solid Tumors (odds ratio, 63.089). Ten of 119 patients experienced grade 3 AEs, with no AE beyond grade 3 observed. CONCLUSION: Lenvatinib RFA sequential therapy might offer favorable tolerability and potential prognostic improvement compared to lenvatinib monotherapy.