Patient Survival Data Research Articles

Mortality risk prediction for primary appendiceal cancer

BackgroundAccurately predicting survival in patients with cancer is crucial for both clinical decision-making and patient counseling. The primary aim of this study was to generate the first machine-learning algorithm to predict the risk of mortality following the diagnosis of an appendiceal neoplasm. MethodsPatients with primary appendiceal cancer in the Surveillance, Epidemiology, and End Results database from 2000 to 2019 were included. Patient demographics, tumor characteristics, and survival data were extracted from the Surveillance, Epidemiology, and End Results database. Extreme gradient boost, random forest, neural network, and logistic regression machine learning models were employed to predict 1-, 5-, and 10-year mortality. After algorithm validation, the best-performance model was used to develop a patient-specific web-based risk prediction model. ResultsA total of 16,579 patients were included in the study, with 13,262 in the training group (80%) and 3,317 in the validation group (20%). Extreme gradient boost exhibited the highest prediction accuracy for 1-, 5-, and 10-year mortality, with the 10-year model exhibiting the maximum area under the curve (0.909 [±0.006]) after 10-fold cross-validation. Variables that significantly influenced the predictive ability of the model were disease grade, malignant carcinoid histology, incidence of positive regional lymph nodes, number of nodes harvested, and presence of distant disease. ConclusionHere, we report the development and validation of a novel prognostic prediction model for patients with appendiceal neoplasms of numerous histologic subtypes that incorporate a vast array of patient, surgical, and pathologic variables. By using machine learning, we achieved an excellent predictive accuracy that was superior to that of previous nomograms.

Characteristics of patients with recurrent retinoblastoma: a survival analysis

BackgroundManagement guidelines and corresponding survival data for patients with recurrent retinoblastoma (RB) are lacking. This study aimed to summarize the clinical characteristics of patients with recurrent RB and analyze their survival outcomes.MethodsWe retrospectively analyzed 68 patients with recurrent RB who underwent treatment in our institution from January 2016 to December 2020. Patients were grouped according to location of recurrence: intraocular, orbital, and distant metastasis.ResultsThe male:female ratio was 1.3:1 and the median age at recurrence was 37.5 months (range, 30.3–62.8). The number of patients in the intraocular recurrence, orbital recurrence, and metastasis groups was 13 (19.1%), 23 (33.8%), and 32 (47.1%), respectively. Thirty patients died, 36 were alive at last follow-up, and two were lost to follow-up. Eye enucleation was performed in 94.1% of patients. Five-year overall survival in patients with intraocular recurrence, orbital recurrence, and metastasis was 84.6%, 69.6%, and 31.3%, respectively (P = 0.001). Most deaths occurred within 2 years of recurrence. Presence of high-risk pathological factors, central nervous system invasion, and absence of combination therapy were independent predictors of worse 5-year overall survival.ConclusionThe rate of eye preservation in survivors of recurrent RB was very low. Although 5-year overall survival in patients who underwent treatment for intraocular and orbital recurrence was high, it was low in those with metastasis. RB patients may need lifelong follow-up for recurrence and secondary malignancy.

Upper gastrointestinal endoscopy procedure volume trends, perioperative mortality, and malpractice claims: Population-based analysis.

Background and study aims Upper gastrointestinal endoscopy (EGD) is one of the most common diagnostic procedures done to examine the foregut, but it can also be used for therapeutic interventions. The main objectives of this study were to investigate trends in EGD utilization and mortality related to it in a national low-threshold healthcare system, assess perioperative safety, and identify and describe patient-reported malpractice claims from the national database. Patients and methods We retrospectively identified patients from the Finnish Patient Care Registry who underwent diagnostic or procedural EGD between 2010 and 2018. In addition, patient-reported claims for malpractice were analyzed from the National Patient Insurance Center (PIC) database. Patient survival data were gathered collectively from the National Death Registry from Statistics Finland. Results During the study period, 409,153 EGDs were performed in Finland for 298,082 patients, with an annual rate of 9.30 procedures per 1,000 inhabitants, with an annual increase of 2.6%. Thirty-day all-cause mortality was 1.70% and 90-day mortality was 3.84%. For every 1,000 patients treated, 0.23 malpractice claims were filed. Conclusions The annual rate of EGD increased by 2.6% during the study, while the rate of interventional procedures remained constant. Also, while the 30-day mortality rate declined over the study period, it is an unsuitable quality metric for EGDs in comprehensive centers because a patient's underlying disease plays a larger role than the procedure in perioperative mortality. Finally, there were few malpractice claims, with self-evident causes prevailing.

Elucidating hepatocellular carcinoma progression: a novel prognostic miRNA–mRNA network and signature analysis

There is increasing evidence that miRNAs play an important role in the prognosis of HCC. There is currently a lack of acknowledged models that accurately predict patient prognosis. The aim of this study is to create a miRNA-based model to precisely forecast a patient’s prognosis and a miRNA–mRNA network to investigate the function of a targeted mRNA. TCGA miRNA dataset and survival data of HCC patients were downloaded for differential analysis. The outcomes of variance analysis were subjected to univariate and multivariate Cox regression analyses and LASSO analysis. We constructed and visualized prognosis-related models and subsequently used violin plots to probe the function of miRNAs in tumor cells. We predicted the target mRNAs added those to the String database, built PPI protein interaction networks, and screened those mRNA using Cytoscape. The hub mRNA was subjected to GO and KEGG analysis to determine its biological role. Six of them were associated with prognosis: hsa-miR-139-3p, hsa-miR-139-5p, hsa-miR-101-3p, hsa-miR-30d-5p, hsa-miR-5003-3p, and hsa-miR-6844. The prognostic model was highly predictive and consistently performs, with the C index exceeding 0.7 after 1, 3, and 5 years. The model estimated significant differences in the Kaplan–Meier plotter and the model could predict patient prognosis independently of clinical indicators. A relatively stable miRNA prognostic model for HCC patients was constructed, and the model was highly accurate in predicting patients with good stability over 5 years. The miRNA–mRNA network was constructed to explore the function of mRNA.

Preoperative CT and survival data for patients undergoing resection of colorectal liver metastases

The liver is a common site for the development of metastases in colorectal cancer. Treatment selection for patients with colorectal liver metastases (CRLM) is difficult; although hepatic resection will cure a minority of CRLM patients, recurrence is common. Reliable preoperative prediction of recurrence could therefore be a valuable tool for physicians in selecting the best candidates for hepatic resection in the treatment of CRLM. It has been hypothesized that evidence for recurrence could be found via quantitative image analysis on preoperative CT imaging of the future liver remnant before resection. To investigate this hypothesis, we have collected preoperative hepatic CT scans, clinicopathologic data, and recurrence/survival data, from a large, single-institution series of patients (n = 197) who underwent hepatic resection of CRLM. For each patient, we also created segmentations of the liver, vessels, tumors, and future liver remnant. The largest of its kind, this dataset is a resource that may aid in the development of quantitative imaging biomarkers and machine learning models for the prediction of post-resection hepatic recurrence of CRLM.

Integrative Multi-Omics Analysis Identifies Transmembrane p24 Trafficking Protein 1 (TMED1) as a Potential Prognostic Marker in Colorectal Cancer.

Several TMED protein family members are overexpressed in malignant tumors and associated with tumor progression. TMED1 belongs to the TMED protein family and is involved in protein vesicular trafficking. However, the expression level and biological role of TMED1 in colorectal cancer (CRC) have yet to be fully elucidated. In this study, the integration of patient survival and multi-omics data (immunohistochemical staining, transcriptomics, and proteomics) revealed that the highly expressed TMED1 was related to the poor prognosis in CRC. Crystal violet staining indicated the cell growth was reduced after knocking down TMED1. Moreover, the flow cytometry results showed that TMED1 knockdown could increase cell apoptosis. The expression of TMED1 was positively correlated with other TMED family members (TMED2, TMED4, TMED9, and TMED10) in CRC, and the protein-protein interaction network suggested its potential impact on immune regulation. Furthermore, TMED1 expression was positively associated with the infiltration levels of regulatory T cells (Tregs), cancer-associated fibroblasts (CAFs), and endothelial cells and negatively correlated with the infiltration levels of CD4+ T cells, CD8+ T cells, and B cells. At last, the CTRP and GDSC datasets on the GSCA platform were used to analyze the relationship between TMED1 expression and drug sensitivity (IC50). The result found that the elevation of TMED1 was positively correlated with IC50 and implied it could increase the drug resistance of cancer cells. This research revealed that TMED1 is a novel prognostic biomarker in CRC and provided a valuable strategy for analyzing potential therapeutic targets of malignant tumors.

Clinical characteristics and survival analysis in patients with isolated pulmonary metastases from colorectal cancer (CRC).

60 Background: Recent studies seem to indicate that patients with metastatic colorectal cancer (mCRC) with exclusive pulmonary metastatic disease have better outcomes than those with other metastatic sites. The aim of this study is to identify differences in clinical and survival characteristics between the two groups in a cohort of a third level hospital. Methods: We retrospectively analyzed a sample of 569 patients with mCRC in a tumor registry from 2015 to 2021, studying clinical and molecular characteristics, as well as overall survival data of patients with isolated pulmonary metastases, versus the rest of patients. Results: Of the total sample analyzed, 61 patients (10.7%) had isolated pulmonary metastases. In these patients, several clinical characteristics were more frequent: primary rectal tumor (52.5% vs 23.4%, p < 0.000), resected primary tumor (95.1% vs 78.9%, p = 0.0026), metachronous metastatic disease (62.3% vs 42%, p = 0.0025) and complete response rate to the first line of treatment (19.3% vs 9.9%, p = 0.026). Furthermore, analytically, these patients were more likely to have normal CEA (75% vs 38.3%, p < 0.000), CA 19.9 (84.3% vs 57.7%, p = 0.0002) and LDH (91.1% vs 66.5%, p = 0.0007) levels. In our cohort, we found no statistically significant differences in tumor mutational status (KRAS, NRAS, BRAF, PI3K and HER2). There were no patients with exclusive pulmonary metastatic disease and microsatellite instability (MSI). 70.3% of patients with isolated pulmonary metastases received lung metastasectomy, and up to 58.3% received a second metastases surgery. We also found a numerical benefit in terms of overall survival (OS) in patients with exclusive metastatic lung disease, although it did not reach statistical signification (median OS 77.3 vs 58.1 months, HR for death 0.70, 95% CI, 0.49 – 1.01, p = 0.083). Conclusions: In our cohort, patients with isolated pulmonary metastases were more likely to have rectal tumors, primary tumor resection, metachronous metastatic disease, higher rate of complete responses and normal CEA, CA 19.9 and LDH levels, with a possible benefit in terms of OS.

Survival benefit and clinical characteristics of patients with metastatic colorectal cancer (mCRC) receiving pulmonary metastasectomy.

59 Background: The role of lung metastasectomy in mCRC remains a topic of particular controversy, being uncertain which patients benefit more from it and whether it leads to better survival outcomes. Our aim was to identify clinical and molecular differences and survival data in a cohort from a tertiary care hospital. Methods: We retrospectively analyzed 115 patients with lung metastases from colorectal cancer (CRC) in a tumor registry from 2015 to 2021, analyzing clinical and molecular characteristics, as well as overall survival (OS) data of patients who received lung metastasectomy versus patients who did not. Results: Among all patients, 36 (31.3%) received pulmonary metastases surgery. Patients undergoing metastases resection had more frequently ECOG 0 (51.4% vs 20.8%, p = 0.0011), resected primary tumor (100% vs 78.5%, p = 0.0026), metachronous metastatic disease (75% vs 46.8%, p = 0.0048) and a single metastatic location (79.4% vs 41%, p = 0.0002). In addition, none of them had BRAF mutation (0% vs 17.1%, p = 0.04); however, no statistically significant differences were found regarding KRAS, NRAS, PI3K, HER2 or presence of microsatellite instability (MSI). Patients who received lung metastasectomy had higher BMI (26.1 vs 24.4, p = 0.037) and lower mean levels of CEA (19.5 vs 142.9, p = 0.007), CA 19.9 (30.6 vs 244.9, p = 0.011) and LDH (159 vs 211.9, p = 0.018). We found an OS benefit in patients undergoing metastatic surgery (median not reached (NR) vs 41.4 months, HR for death 0.27, 95% CI, 0.14 - 0.53, p < 0.000); a multivariate analysis confirmed that this benefit was independent from the characteristics mentioned above. The median progression-free survival (PFS) after metastases resection was 53.3 months. Conclusions: In our study, patients who were more likely to receive lung metastasectomy were those with ECOG 0, resected primary tumor, metachronous disseminated disease, a single metastatic location, native BRAF mutation status and low CEA, CA 19.9 and LDH levels, with a significant OS benefit associated.

A single-center, real-world experience of atezolizumab plus bevacizumab as first-line therapy in patients with unresectable hepatocellular carcinoma, including patients with advanced cirrhosis.

445 Background: Atezolizumab plus bevacizumab (A+B) is approved by the Food and Drug Administration (FDA) for treatment of advanced stage hepatocellular carcinoma (HCC) as first line systemic therapy following results of the IMBRAVE150 trial. Since its approval, limited real-world data is available. The benefit of this treatment in patients with advanced cirrhosis is still unclear, especially in patients with Child Pugh (CP) B cirrhosis. We aim to supplement the trial data with real world outcomes of individuals with unresectable HCC treated with (A+B) in the first line setting including patients with advanced cirrhosis. Methods: This was a single-center, retrospective analysis of patients with advanced HCC treated with A+B as first line systemic therapy between May 2020-January 2023. Patient characteristics, HCC stage, treatment information, adverse events and survival data were collected. Outcomes evaluated included progression free survival (PFS), overall survival (OS), overall response rate (ORR) using RECIST 1.1 and adverse events (AE) rate according to CTCAE v5. R v4.2.1 was used for analysis. Results: We identified a total of 41 patients with advanced stage HCC who received A+B as first line systemic therapy. The median age at diagnosis was 69 years (range 42 – 85). 34(83%) of the patients were males. 8(20%) of the patients were African American. 7(17%) patients had CP B cirrhosis. Median PFS on A+B among all patients was 10.82 months (95% CI: 5.38 – 16.26). Median OS from time of A+B initiation was 14.01 months (95% CI: 10.67 – 17.34). Median OS and PFS were significantly shorter among CP B patients, 6.84(95% CI: NE – 19.36, p = 0.003) and 6.8(95% CI: NE -19.33, p = 0.016) respectively. Hazard ratio (HR) for death from any cause among CP B patients was 4.87(95% CI: 1.35 – 17.48, p <0.01) compared to others. ORR was 31.42%. 10/23(39.13%) patients with CP A had overall response, while 1/7(14.28%) patients with CP B had overall response. AE of any grade was observed in 30(73.2%) patients.10(24.4%) patients had grade 3 or more events, 2(28.5%) among CP B patients. 1(14.2%) had GI bleed among CP B patients, while 4(9.7) patients had GI bleed overall. Common adverse events included fatigue (26.8%), anorexia (26.8%), aspartate aminotransferase (AST) elevation (14.6%), proteinuria (17%), rash (21.9%). Conclusions: Efficacy profile of A+B appears to be sustained in the real world. While the efficacy is inferior in CP B liver disease, A+B remains a viable option for these patients with limited treatment options and acceptable tolerability. Our study adds to the body of evidence for real world data with A+B.

Abstract B117: Phase 1 study of CM24 in combination with nivolumab in patients with advanced pancreatic cancer - Survival, potential biomarker and effect on neutrophil extracellular traps (NETs)

Abstract Background: The monoclonal antibody CM24 blocks the activity of carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), which is known to have several important roles in cancer progression, immune evasion, and metastasis. The homophilic interaction of CEACAM1 on tumor cells and tumor infiltrating lymphocytes (TILs) silences the anti-tumor immunity. Additionally, CEACAM1 is part of the neutrophil extracellular trap (NET) complex. NETs are regarded as an important component in the tumor microenvironment, which contribute to metastasis and immune evasion. Previously we have demonstrated direct binding of CM24 to NETs and inhibition of NET-induced cancer cell migration and tumor metastasis by the antibody. Here, we present the results from the dose escalation part of a Phase 1/2 study of CM24 and nivolumab (NCT 04731467) and the findings of exploratory studies that were conducted as part of this trial. Methods: In the dose escalation part of the study, 11 pancreatic ductal adenocarcinoma (PDAC) patients who received 2 prior lines of therapy were administered CM24 at 10, 15 and 20mg/kg q2w and nivolumab at 480mg q4w. Levels of CEACAM1 and myeloperoxidase (MPO) were measured in serum by ELISA. Pretreatment biopsies from 8 evaluable PDAC patients were analyzed, along with pretreatment and on treatment serum samples. Quantitative multiplex IF and immunohistochemistry (IHC) were used to evaluate CEACAM1, PDL1, TIM3 and CEACAM1-positive TILs in patient biopsies. Results: Nine PDAC patients were evaluable for exploratory efficacy assessment with a median OS of 4.5 (95% CI 2.0-11.1) months, including 1 confirmed PR and 2 pts with SD for a disease control rate of 33%. Percentage of CEACAM1+TILs in patient biopsies ranged between 0% and 10%, and a cutoff rate to define low (0-5%) vs. high (> 5%) expression was used to stratify the patient survival data. High CEACAM1+TILs (median of 10%) were measured in 3/8 PDAC patients with median survival of 11.1 months (range: 9.6-14.6 months) compared to 5/8 patients with low CEACAM1+TILs (median 2%) who exhibited shorter survival (range: 2-4.5 months), suggesting positive association (p=0.017). IHC analysis of CEACAM1 further revealed CEACAM1-positive NETs in the biopsies of all PDAC patients. In serum, enhanced levels of the NET biomarker MPO were detected in PDAC patients (n=10) as compared to healthy volunteers (n=30), demonstrating a 3-fold difference in the mean value (p<0.01). Interestingly, MPO levels decreased by an average of 40% (p<0.05) across all dose levels within 2 weeks of CM24 therapy. Additional findings will be presented at the conference. Conclusions: CM24 in combination with nivolumab shows promising initial activity results and a favorable safety profile in PDAC patients who have progressed after second-line therapy. The positive association between the level of CEACAM1+TILs and OS as well as CM24 effects on NETs, advocate for the role of CM24 in controlling immune evasion. These 2 potential biomarkers are being investigated in the ongoing randomized Phase 2 study. Citation Format: Erkut Borazanci, Shubham Pant, Ruth Perets, Talia Golan, Mohammed Najeeb Al Hallak, Michael Cecchini, Tomer Maierson, Hava Ben David, Michael Schickler, Hadas Reuveni. Phase 1 study of CM24 in combination with nivolumab in patients with advanced pancreatic cancer - Survival, potential biomarker and effect on neutrophil extracellular traps (NETs) [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B117.

Construction of an abnormal glycosylation risk model and its application in predicting the prognosis of patients with head and neck cancer

Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumor of the head and neck, and the incidence rate is increasing year by year. Protein post-translational modification, recognized as a pivotal and extensive form of protein modification, has been established to possess a profound association with tumor occurrence and progression. This study employed bioinformatics analysis utilizing transcriptome sequencing data, patient survival data, and clinical data from HNSCC to establish predictive markers of genes associated with glycosylation as prognostic risk markers. The R procedure WGCNA was employed to construct a gene co-expression network using the gene expression profile and clinical characteristics of HNSCC samples. Multiple Cox Proportional Hazards Regression Model (Cox regression) and LASSO analysis were conducted to identify the key genes exhibiting the strongest association with prognosis. A risk score, known as the glycosylation-related genes risk score (GLRS), was subsequently formulated utilizing the aforementioned core genes. This scoring system facilitated the classification of samples into high-risk and low-risk categories, thereby enabling the prediction of patient prognosis. The association between GLRS and clinical variables was examined through both univariate and multivariate Cox regression analysis. The validation of six core genes was accomplished using quantitative real-time polymerase chain reaction (qRT-PCR). The findings demonstrated noteworthy variations in risk scores among subgroups, thereby affirming the efficacy of GLRS in prognosticating patient outcomes. Furthermore, a correlation has been observed between the risk-scoring model and immune infiltration. Moreover, significant disparities exist in the expression levels of diverse immune checkpoints, epithelial-mesenchymal transition genes, and angiogenic factors between the high and low-risk groups.

Meta-analysis of the efficacy of postoperative adjuvant chemotherapy for stage IB non-small cell lung cancer.

Many clinical trials have shown that postoperative adjuvant chemotherapy can provide a survival benefit for patients with stage IB non-small cell lung cancer. However, whether adjuvant chemotherapy should be routinely given after surgery remains controversial. Therefore, we performed a meta-analysis to investigate the efficacy of adjuvant chemotherapy versus surgery alone for stage IB non-small cell lung cancer (NSCLC). Relevant retrospective studies or randomized controlled trial comparing the efficacy of postoperative adjuvant chemotherapy versus observation on the survival outcomes of NSCLC patients up to October 30, 2023 were searched in PubMed, Web of Science, EMBASE, Cochrane Library, VIP database, Wanfang database, and China National Knowledge Internet database. Patient survival data, population characteristics, and other relevant information were extracted, and data were analyzed using Review Manager 5.4. The primary endpoints included overall survival, disease-free survival, and recurrence-free survival. A total of 13 randomized controlled trials or cohort studies including 19,442 patients were included. The results of the meta-analysis showed that postoperative adjuvant chemotherapy in patients with stage IB NSCLC had better overall survival (odds ratio [OR] = 1.25, 95% confidence interval [CI] 1.19-1.31, P < .00001) and disease-free survival or recurrence-free survival (OR = 1.57, 95% CI 1.3-1.9, P < .00001) compared with observation; and the 4-year survival rate of patients who received postoperative adjuvant chemotherapy was better than the observation group (OR = 1.52, 95% CI 1.05-2.18, P = .03); and the 8-year survival rate of patients receiving postoperative adjuvant chemotherapy (OR = 1.5, 95% CI 0.94-2.4, P = .09) was comparable to the observation group. Receiving postoperative adjuvant chemotherapy improved people's survival and prolonged disease-free survival and recurrence-free survival in patients with stage IB non-small cell lung cancer compared with surgery alone.

Correlation between Angiotensin Inhibitor Administration and Longer Survival in Patients Who Underwent Curative Resection for Pancreatic Cancer.

The microenvironment of pancreatic ductal adenocarcinoma (PDAC) with extensive desmoplastic stroma contributes to aggressive cancer behavior. Angiotensin system inhibitors (ASIs) reduce stromal fibrosis and are a promising therapeutic strategy. The purpose of this study was to examine how ASIs affected the oncological results of patients who had their PDAC removed. A retrospective assessment was conducted on the clinicopathological and survival data of patients who received curative resection for PDAC at Severance Hospital between January 2012 and December 2019. A total of 410 participants (228 male and 182 female), with a median follow-up period of 12.8 months, were included in this study. Patients were divided into three groups, based on ASI use and history of hypertension: group 1, normotensive and never used ASI (n=210, 51.2%); group 2, ASI non-users with hypertension (n=50, 12.2%); and group 3, ASI users with hypertension (n=150, 36.6%). The three groups did not differ significantly in terms of age, sex, kind of operation, T and N stages, or adjuvant and neoadjuvant therapy. Moreover, there was no discernible difference in disease-free survival between those who used ASI and those who did not (p=0.636). The 5-year overall survival (OS) rates in groups 1, 2, and 3 were 52.6%, 32.3%, and 38.0%, respectively. However, the OS rate of ASI users was remarkably higher than that of non-users (p=0.016). In patients with resected PDAC, ASI is linked to longer survival rates. Furthermore, for individuals with hypertension, ASI in conjunction with conventional chemotherapy may be an easy and successful treatment option.

Silencing HDAC1 Expression Regulates Extracellular Regulated Protein Kinases/Mitogen-Activated Protein Kinase Signaling Activation and Enhances Chemosensitivity of Ovarian Carcinoma

Objective: Cisplatin (DDP)-based therapy is frequently employed as a first-line chemotherapy for ovarian carcinoma (OC). ERK/mitogen-activated protein kinase (MAPK), as a widely studied axis with cancer-promoting action, is reported to be essential in mediating chemoresistance in many cancer cells. This study investigated the effect of HDAC1 expression on the chemosensitivity of OC via regulation of the ERK/MAPK axis. Methods: Fifty-eight cases of OC and adjacent tissue specimens were acquired, as well as the survival data of patients with OC in the Cancer Genome Atlas. To detect HDAC1 in tissues, a HDAC1-DNA probe was constructed, and patients with different HDAC1 levels were analyzed for survival. HDAC1 levels were also detected in SKOV3 and SKOV3/DDP cells. HDAC1 siRNA was used to interfere with HDAC1 expression, after which the sensitivity to DDP sensitivity and changes in apoptosis of tumor cells were detected using the MTT assay and flow cytometry, respectively. Western blotting quantified the expression of ERK/MAPK axis-related proteins. Results: HDAC1 was highly expressed in OC tissues, with a high expression significantly related to adverse outcomes of patients. Compared with that in SKOV3 cells, SKOV3/DDP cells showed decreased sensitivity to DDP and increased HDAC1 expression. After transfection of HDAC1-siRNA, SKOV3/DDP cell sensitivity to DDP increased, p38 MAPK, ERK1/2, and JNK phosphorylation levels decreased, and the apoptosis rate increased markedly; transfection with an ERK agonist reversed the inhibitory action of HDAC1-siRNA against cells. Conclusions: Silencing HDAC1 expression significantly reduced the chemoresistance of DDP-resistant OC cell lines and promoted apoptosis, and its mechanism is related to inhibition of ERK/MAPK activation.

A Concept for Preoperative and Intraoperative Molecular Imaging and Detection for Assessing Extent of Disease of Solid Tumors.

The authors propose a concept of "systems engineering," the approach to assessing the extent of diseased tissue (EODT) in solid tumors. We modeled the proof of this concept based on our clinical experience with colorectal carcinoma (CRC) and gastrinoma that included short and long-term survival data of CRC patients. This concept, applicable to various solid tumors, combines resources from surgery, nuclear medicine, radiology, pathology, and oncology needed for preoperative and intraoperative assessments of a patient's EODT. The concept begins with a patient presenting with biopsy-proven cancer. An appropriate preferential locator (PL) is a molecule that preferentially binds to a cancer-related molecular target (i.e., tumor marker) lacking in non-malignant tissue and is the essential element. Detecting the PL after an intravenous injection requires the PL labeling with an appropriate tracer radionuclide, a fluoroprobe, or both. Preoperative imaging of the tracer's signal requires molecular imaging modalities alone or in combination with computerized tomography (CT). These include positron emission tomography (PET), PET/CT, single-photon emission computed tomography (SPECT), SPECT/CT for preoperative imaging, gamma cameras for intraoperative imaging, and gamma-detecting probes for precise localization. Similarly, fluorescent-labeled PLs require appropriate cameras and probes. This approach provides the surgeon with real-time information needed for R0 resection.

Prognostic Significance of Tumor Mutation Burden among Patients with Non-small Cell Lung Cancer Who Received Platinum-based Adjuvant Chemotherapy: An Exploratory Study.

This study aimed to investigate the prognostic significance of tumor mutation burden (TMB) among patients with non-small cell lung cancer (NSCLC) who received platinum-based adjuvant chemotherapy. Tumor tissue specimens after surgical resection were collected for DNA extraction. Somatic mutation detection and TMB analysis were conducted using next-generation sequencing (NGS). Recurrence status of the patients was assessed in the hospital during the adjuvant chemotherapy period, and long-term survival data of patients were obtained by telephone follow-up. Univariate analysis between TMB status and prognosis was carried out by survival analysis. A retrospective review of 78 patients with non-squamous NSCLC who received platinum-based adjuvant chemotherapy showed a median disease-free survival of 3.6 years and median overall survival (OS) of 5.3 years. NGS analysis exhibited that the most common mutated somatic genes among the 78 patients were tumor suppressor protein p53 (TP53), epidermal growth factor receptor, low-density lipoprotein receptor related protein 1B, DNA methyltransferase 3 alpha and FAT atypical cadherin 3, and their prevalence was 56.4%, 48.7%, 37.2%, 30.7%, and 25.6%, respectively. TMB status was divided into TMB-L (≤ 4.5/Mb) and TMB-H (> 4.5/Mb) based on the median TMB threshold. Relevance of TMB to prognosis suggested that the median OS of patients with TMB-L was significantly longer than that of patients with TMB-H (NR vs. 4.6, P = 0.014). Higher TMB status conferred a worse implication on OS among patients with non-squamous NSCLC who received platinum-based adjuvant chemotherapy.

Cost-effectiveness of volume computed tomography in lung cancer screening: a cohort simulation based on Nelson study outcomes

Objectives This study aimed to evaluate the cost-effectiveness of lung cancer screening (LCS) with volume-based low-dose computed tomography (CT) versus no screening for an asymptomatic high-risk population in the United Kingdom (UK), utilising the long-term insights provided by the NELSON study, the largest European randomized control trial investigating LCS. Methods A cost-effectiveness analysis was conducted using a decision tree and a state-transition Markov model to simulate the identification, diagnosis, and treatments for a lung cancer high-risk population, from a UK National Health Service (NHS) perspective. Eligible participants underwent annual volume CT screening and were compared to a cohort without the option of screening. Screen-detected lung cancers, costs, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) were predicted. Results Annual volume CT screening of 1.3 million eligible participants resulted in 96,474 more lung cancer cases detected in early stage, and 73,825 fewer cases in late stage, leading to 53,732 premature lung cancer deaths averted and 421,647 QALYs gained, compared to no screening. The ICER was £5,455 per QALY. These estimates were robust in sensitivity analyses. Limitations Lack of long-term survival data for lung cancer patients; deficiency in rigorous micro-costing studies to establish detailed treatment costs inputs for lung cancer patients. Conclusions Annual LCS with volume-based low-dose CT for a high-risk asymptomatic population is cost-effective in the UK, at a threshold of £20,000 per QALY, representing an efficient use of NHS resources with substantially improved outcomes for lung cancer patients, as well as additional societal and economic benefits for society as a whole. These findings advocate evidence-based decisions for the potential implementation of a nationwide LCS in the UK.

Bayes Estimator of Exponential Distribution Parameters of Type II Censored Data with Linear Exponential Loss Function Method Based on Jeffrey Priors

Survival analysis is often used in the application of analyzing the survival of an object such as living things or objects. This analysis is identical to data censoring which is divided into three, namely: type I, II, and III censored data. Type II censored data is data censoring done by determining the number of objects to be analyzed from the total number of observation objects . Type II censored data is used when the analysis is intended to maximize the results of the analysis. Bayesian Linear Exponential (LINEX) loss function is one method that can be used to estimate parameters in survival analysis by minimizing the expected value of LINEX. The purpose of this study is to determine the Bayesian LINEX loss function parameter estimation on type II censored data using exponential distribution. This method uses the concept of posterior distribution and prior distribution. The prior distribution used is the Jeffrey prior distribution which has objective properties and is based on Fisher information theory The application of the parameter estimation results is carried out on the survival data of lung cancer patients obtained from the North Central Cancer Treatment Group. Based on the results of parameter estimation, it is concluded that the greater the value of the controller (a) can produce a smaller value of parameter estimation results (θ^) . The results of this study can be used as a reference in conducting survival tests using type II censored exponential distribution data using the LINEX loss function method based on Jeffrey priors.

Genome Sequencing-Based Prognosis, Mutational Analysis, and Survival Rate of Pediatric Acute Myeloid Leukemia

Abstract Introduction/Objective Pediatric Acute Myeloid Leukemia (AML) is a rare diagnosis that once carried a poor prognosis, but with recent improvement, the survival rate now reaches 80%. Although studies of most genetic mechanisms of AML involved adult studies, but dissimilar mutational profiles and treatment responses in pediatric patients have become evident. Information regarding pediatric AML-specific whole genome sequencing, a prognostic prediction system, and overall survival is limited. Hence, we aimed to analyze the genomic profile, epidemiological characteristics, and overall survival of pediatric AML. Methods/Case Report We utilized cBioPortal cancer genomics [The Cancer Genome Atlas (TCGA) PanCancer Atlas, TCGA Firehose Legacy, and TCGA Nature 2013] to study genetic mutations associated with pediatric AML. Epidemiological characteristics and genetic profiles available on cBioportal were evaluated. Gene mutations with the most statistically significant shortest overall survival and survival in days from the samples were used for gene query, and survival rate with the most common mutations was calculated. Log-rank test and Kaplan–Meier estimators were used in analyzing the survival function. Patients with two or more overlapping mutations were excluded. Results (if a Case Study enter NA) We identified 899 patients with Pediatric AML, out of 886 had all demographic data available, 50.8% were males, 71.6% were Caucasian, and 11.3% were African American. 568 (63.2%) were alive, and 318 (35.4%) were deceased. 159 patients were diagnosed at less than or equal to 2 years of age, and 150 patients had 80-90% blasts in their samples. 440 (42.9%) had relapse of disease at the bone marrow, whereas 72 (7.0%) had relapse at other sites. The common mutations associated with reduced survival were C4ORF36, HERC5, GPRIN3, NFKB1, NUP88, QRFPR, SPRY1, and UNC5C. Median survival data of patients was available for GPRIN3, NFKB1, NUP88, SPRY1, UNC5C, and was 25.00, 11.00, 15.00, 59.00, and 14.00 months respectively. Comparison with the unaltered group was not available (p &amp;lt; 0.0001). Survival was lowest amongst NFKB1 (11.00 months), NUP88 (15.00 months), and UNC5C (14.00 months). In survival analysis, the same genes were associated with lowest survival after initial diagnosis (p = 7.301e-4). Conclusion Our study found that NFKB1, NUP88, and UNC5C genes were associated with the worst prognosis in pediatric AML with median survival of 11.00, 15.00, and 14.00 months. Furthermore it may result in improve the prognosis of these patients.

The efficacy of chemotherapy re-challenge in third-line setting for metastatic colorectal cancer patients: a real-world study

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.