Prognostic Factor For Overall Survival Research Articles

Comprehensive genomic and transcriptomic characterization of high-grade gastro-entero-pancreatic neoplasms.

High-grade gastro-entero-pancreatic neoplasms (HG GEP-NENs) can be stratified according to their morphology and Ki-67 values into three prognostic classes: neuroendocrine tumors grade 3 (NETs G3), neuroendocrine carcinomas with Ki-67 < 55% (NECs <55) and NECs with Ki-67 ≥ 55% (NECs ≥55). We analyzed a cohort of 49 HG GEP-NENs by targeted Next-Generation Sequencing (TrueSight Oncology 500), RNA-seq, and immunohistochemistry for p53, Rb1, SSTR-2A, and PD-L1. Frequent genomic alterations affected TP53 (26%), APC (20%), KRAS and MEN1 (both 11%) genes. NET G3 were enriched in MEN1 (p = 0.02) mutations, while both NECs groups were enriched in TP53 (p = 0.001), APC (p = 0.002) and KRAS (p = 0.02) mutations and tumors with TMB ≥ 10 muts/Mb (p = 0.01). No differentially expressed (DE) gene was found between NECs <55% and NECs ≥55%, while 1129 DE genes were identified between NET G3 and NECs. A slight enrichment of CD4+ and CD8+ T cells in NECs and of cancer-associated fibroblasts and macrophages (M2-like) in NET G3. Multivariate analysis identified histologic type and Rb1 loss as independent prognostic factors for overall survival. This study showed that GEP-NET G3 and GEP-NECs exhibit clear genomic and transcriptomic differences, differently from GEP-NECs <55% and GEP-NECs ≥55%, and provided molecular findings with prognostic and potentially predictive value.

Clinical Significance of Primary Tumor Resection in Perihilar Cholangiocarcinoma with Positive Peritoneal Lavage Cytology.

The prognostic impact of positive peritoneal lavage cytology (CY+) in patients with perihilar cholangiocarcinoma (PHC) remains unclear. The present study investigated the clinical significance of primary tumor resection of CY+ PHC. We retrospectively evaluated 282 patients who underwent surgery for PHC between September 2002 and March 2022. The patients' clinicopathological characteristics and survival outcomes were compared between the CY negative (CY-) resected (n = 262), CY+ resected (n = 12), and CY+ unresected (n = 8) groups. Univariate and multivariate analyses were performed to identify prognostic factors for overall survival. The expected residual liver volume was significantly higher in the CY+ resected group (61%) than in the CY- resected (47%) and CY+ unresected (37%) groups (p = 0.004 and 0.007, respectively). The CY+ resected group had a higher administration rate of postoperative therapy than the CY- resected group (58% vs. 16%, p = 0.002). Overall survival of the CY+ resected group was similar to that of the CY- resected group (median survival time [MST] 44.5 vs. 44.6, p = 0.404) and was significantly better than that of the CY+ unresected group (MST 44.5 vs. 17.1, p = 0.006). CY positivity was not a prognostic factor according to a multivariate analysis in patients with primary tumor resection. The CY+ resected group showed better survival than the CY+ unresected group and a similar survival to that of the CY- resected group. Resection of the primary tumor with CY+ PHC may improve the prognosis in selected patients.

Multiomics sequencing and immune microenvironment characteristics define three subtypes of small cell neuroendocrine carcinoma of the cervix.

Small cell cervical carcinoma (SCCC) is the most common neuroendocrine tumor in the female genital tract, with an unfavorable prognosis and lacking an evidence-based therapeutic approach. Until now, the distinct subtypes and immune characteristics of SCCC combined with genome and transcriptome have not been described. We performed genomic (n = 18), HPV integration (n = 18), and transcriptomic sequencing (n = 19) of SCCC samples. We assessed differences in immune characteristics between SCCC and conventional cervical cancer, and other small cell neuroendocrine carcinomas, through bioinformatics analysis and immunohistochemical assays. We stratified SCCC patients through non-negative matrix factorization and described the characteristics of these distinct types. We further validated it using multiplex immunofluorescence (n = 77) and investigated its clinical prognostic effect. We confirmed a high frequency of PIK3CA and TP53 alterations and HPV18 integrations in SCCC. SCCC and other small cell carcinoma had similar expression signatures and immune cell infiltration patterns. Comparing patients with SCCC to those with conventional cervical cancer, the former presented immune excluded or 'desert' infiltration. The number of CD8+ cells in the invasion margin of SCCC patients predicted favorable clinical outcomes. We identified three transcriptome subtypes: an inflamed phenotype with high-level expression of genes related to the MHC-II complex (CD74) and IFN-α/β (SCCC-I), and two neuroendocrine subtypes with high-level expression of ASCL1 or NEUROD1, respectively. Combined with multiple technologies, we found that the neuroendocrine groups had more TP53 mutations and SCCC-I had more PIK3CA mutations. Multiplex immunofluorescence validated these subtypes and SCCC-I was an independent prognostic factor of overall survival. These results provide insights into SCCC tumor heterogeneity and potential therapies. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Reduced Risk of Severe Radiation-Induced Lymphopenia in Carbon Ion Radiation Therapy for Locally Advanced Pancreatic Cancer: A Comparative Analysis of Carbon Versus Photon Therapy.

Radiation-induced lymphopenia (RIL) is associated with poor prognosis in patients with locally advanced pancreatic cancers. However, there are no reports comparing the effects of carbon ion radiation therapy (CIRT) and photon beam radiation therapy (RT) on the development of RIL. Differences in RIL after CIRT or photon beam RT and predictive factors for RIL in patients with locally advanced pancreatic cancer were investigated. This retrospective study cohort included 834 patients who received concurrent chemoradiotherapy (CCRT) in 2 separate institutions: 337 and 497 in the CIRT and photon beam RT groups, respectively. Severe RIL was defined as an absolute lymphocyte count (ALC) <0.5 × 109 cells/L. A 1:1 propensity score-matching analysis was performed between the CIRT and photon beam RT groups. Patients were categorized into 3 groups according to the development of recovery from severe RIL: no severe RIL (Group A), recovery from severe RIL (Group B), and no recovery from severe RIL (Group C). Logistic regression analysis was performed to identify the predictive value of severe RIL. The prognostic factors of overall survival (OS) were determined using Cox regression analysis. After propensity score matching, the baseline ALC and planning target volume of the CIRT and photon beam RT groups were comparable. During CCRT, the ALC of the entire cohort decreased and was significantly lower in the photon beam RT group than in the CIRT group (P < .001). Multivariate logistic regression analysis showed that CIRT reduced severe RIL more than photon beam RT. After adjusting for other factors, the RT modality and RIL were significantly associated with OS. Photon beam RT showed a significantly worse OS than CIRT, and Group C showed a significantly worse OS than Group A. CIRT seems to reduce the development of severe RIL. The RT modality and development/recovery from severe RIL were associated with OS in patients who received CCRT for locally advanced pancreatic cancer. The reduction of severe RIL through optimized RT may be essential for improving treatment outcomes.

Abstract PO5-02-12: Comparison of survival outcomes according to axillary ultrasonography findings and cytology results in early-stage breast cancer patients

Abstract Purpose: Axillary lymph node dissection and sentinel lymph node biopsy are associated with increased risk of post-surgical complications including lymphedema and recent trials have raised questions about the therapeutic benefit of axillary operation in early-stage breast cancer patients. While treatment options for lymph nodes with negative findings on axillary ultrasonography (AUS) or positive findings on fine needle aspiration biopsy (FNAB) are evident, data regarding lymph nodes that are suspicious on AUS but negative by FNAB are limited. Thus, we aimed to compare clinicopathological characteristics of AUS positive and FNAB negative patients with those of AUS negative or FNAB positive patients. Materials and Methods: Medical records of patients who underwent breast cancer surgery between January 2010 and December 2017 were reviewed. Patients were grouped into the following three groups: (a) negative findings on AUS, (b) suspicious findings on AUS but negative on FNAB, (c) and FNAB positive. A total of 4,506 patients were included for analysis, with 3,771 patients with no suspicious lymph nodes on AUS, 557 patients who had suspicious AUS findings but were negative on FNAB, and 178 patients with positive findings on both AUS and FNAB. Primary endpoints were disease free survival (DFS) and recurrence free survival (RFS), and secondary endpoint was overall survival (OS). Results: At a median follow-up period of 92 months, DFS and RFS was significantly higher in the AUS negative group compared to the other two groups (10-year-DFS: 91.6% vs 87.5% vs 75.7%, 10-year-RFS: 95.0% vs 89.9% vs 77.1%, p &amp;lt; 0.001). In terms of OS, AUS negative group and the AUS positive and FNAB negative group did not show statistically significant survival difference (10-year-OS: 94.5% vs 92.8%, p = 0.061), while the FNAB positive group showed significantly lower survival rates (10-year-OS: 81.8%, p &amp;lt; 0.001). Multivariable analysis revealed that not AUS positive and FANB negative but positive FNAB was significantly associated with poor RFS. Moreover, hormone receptor (HR) positive and HER2 negative subtype showed poor DFS and RFS in subgroup analysis. Conclusion: Early breast cancer patients with suspicious findings on AUS but negative FNAB results had similar OS but inferior DFS and RFS compared to those with negative features on AUS, especially in HR(+)HER2(-) subtype. While further prospective trials are warranted to determine whether additional treatment is necessary, close surveillance is recommended for this subgroup of patients. Figure1. Overall survial and Disease free survival according to axillay US and FNAB status Table1. patients' characteristics Table2. prognostic factors for overall survival and disease free survival related to axillary US and FNAB status Citation Format: Suk Jun Lee. Comparison of survival outcomes according to axillary ultrasonography findings and cytology results in early-stage breast cancer patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-02-12.

Abstract PO4-04-05: HER2 immunohistochemistry (IHC) expression in HER2-positive (HER2-pos) metastatic breast cancer (mBC): clinical and prognostic differences between IHC 2+ and IHC 3+ populations

Abstract Background: The exploration of heterogeneity in mBC has gained significant interest in optimizing therapeutic strategies. While the impact of differential HER2 IHC staining has been extensively studied in HER2-low neoplasms, limited data is available regarding IHC 2+ and IHC 3+ categories in HER2-pos mBC. The aim of our study is to compare, the clinical variables, metastatic patterns, and prognosis between patients classified as IHC 2+ and IHC 3+ in HER2-pos mBC. Methods: Pts with HER2 pos mBC, determined by HER2 IHC staining of 3+ or 2+ with amplification at the in situ hybridization assay, were selected from the GIM14 study database for analysis. Associations among variables were assessed by conducting logistic regression analyses. Additionally, prognostic factors for overall survival (OS) and time to treatment failure (TTF) were evaluated using both uni- and multi-variable Cox regression models. Results: A total of 766 HER2-pos mBC pts were included in the analysis. Among them, 302 (39%) had IHC score of 2+ and 464 (61%) had a IHC score of 3+. Central nervous system (CSN) metastases (mts) were observed in 68 (9%) pts (32% IHC 2+; 68% IHC 3+), lymph node (LN) mts in 330 (43%) pts (46% IHC 2+; 54% IHC 3+), lung (LU) mts in 182 (24%) pts (46% IHC 2+; 54% IHC 3+), liver (LI) mts in 227 (30%) pts (45% IHC 2+, 55% IHC 3+), skin (SK) mts in 68 (9%) pts (28% IHC 2+; 72% IHC 3+) and pleural (PL) mts in 40 (5%) pts (47% IHC 2+, 53% IHC 3+). In univariable (uni) analysis, IHC 3+ compared to IHC 2+ was significantly associated with SK mts (OR 1.76, P=0.043) and less likely to be associated with LI (OR 0.71, P=0.031), LU (OR 0.70, P =0.036), and LN (OR 0.63, P=0.002) mts. In multivariable (multi) analysis, LN mts maintained statistical significance (OR 0.62, P=0.004). In subgroup analysis, among IHC 3+ patients, factors associated with worse OS pts were neo Tx (HR 1.55, P=0.032), adjuvant radiotherapy (HR 1.34, P=0.042), neo ChT (HR 1.63, P=0.002), CNS mts (HR 1.98, P=0.002), and LI mts (HR 1.68, P&amp;lt; 0.0001). In multi analysis, CNS mts (HR 1.73, P=0.028) and LI mts (HR 1.47, P=0.017) remained prognostic for IHC 3+ subgroup. The only factor associated with worse OS in IHC 2+ pts was LI mts (HR 1.67, P=0.005). Multi analysis in the overall HER2-pos population identified neo chemotherapy (ChT) (HR 1.49, P=0.009), CNS mts (HR 1.53, P=0.003) and PL mts (HR 1.50, P=0.036) as negative prognostic factors for OS, while PL mts (HR 1.74, P=0.048) were associated with a shorter time to treatment failure (TTF). Conclusions: Our exploratory data revealed that HER2-pos mBC with a IHC score of 3+ is less likely to be associated with LN mts and with visceral mts. The site of mts has prognostic significance, as CNS mts are associated with worse OS in pts with an IHC score of 3+ pts, while LI mts are associated with worse OS in both IHC 2+ and 3+ subgroups. However, the IHC score itself (2+ or 3+) does not have independent prognostic value. The relationship between HER2 IHC staining and treatment outcomes requires further investigation to better understand its potential impact on clinical practice. Citation Format: Arianna Dri, Eva Blondeaux, Claudia Bighin, Simona Gasparro, Stefania Russo, Lorenzo Foffano, Palma Pugliese, Andrea Fontana, Enrico Cortesi, Antonella Ferzi, Ferdinando Riccardi, Valentina Sini, Luca Boni, Alessandra Fabi, Filippo Montemurro, Michelino De Laurentiis, Grazia Arpino, Lucia Del Mastro, Lorenzo Gerratana, Fabio Puglisi. HER2 immunohistochemistry (IHC) expression in HER2-positive (HER2-pos) metastatic breast cancer (mBC): clinical and prognostic differences between IHC 2+ and IHC 3+ populations [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-04-05.

Abstract PO3-17-02: Analysis of clinical benefit in the real world of HER2-positive metastatic breast cancer following the development of anti-HER2 therapeutics over the past 20 years

Abstract Analysis of clinical benefit in the real world of HER2-positive metastatic breast cancer following the development of anti-HER2 therapeutics over the past 20 years Ahrong Ham1, Sewon Lee1, Jungmin Jo1, Soo Ji Hong2, Ji Eun Lee2, Haena Lee2, Sungchan Gwark2, Jeongshin An2, Hyun Goo Kim2, Jun Woo Lee2, Joohyun Woo2, Woosung Lim2, Byung-In Moon2, Sei Hyun Ahn2, Hye Ah Lee3, Kyoung Eun Lee1 1 Division of Hematology and Oncology, Department of Internal Medicine, Ewha Womans University Mokdong hospital, Ewha Womans University College of Medicine, Seoul, Republic of Korea 2 Department of Surgery, Ewha Womans University Mokdong hospital, Ewha Womans University College of Medicine, Seoul, Republic of Korea 3 Clinical Trial Center, Ewha Womans University Mokdong hospital, Ewha Womans University College of Medicine, Seoul, Republic of Korea Purpose: Over the last two decades, treatment landscapes for human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer (MBC) have shown remarkable growth with the development of drugs targeting HER2. The standard of care for HER2+ MBC has continued to change with the ongoing development of new anti-HER2 therapies. We aimed to provide a comprehensive analysis of HER2-targeted therapies, clinical characteristics, and treatment outcomes in real-world practice of HER2+ MBC patients over the past 20 years. Methods: Patients who received palliative chemotherapy with HER2+ MBC between 2000 and 2022 were analyzed. We derived cohorts of two groups with or without anti-HER2 containing therapies. Patients receiving multiple anti-HER2 therapies throughout the entire period of treatment were further analyzed according to treatment regimen. The progression-free survival for palliative first-line (PFS1), and overall survival (OS) were compared between groups. A multivariate Cox regression model was used to investigate predictors of survival outcome in HER2+ MBC. Results: A total of 185 patients were analyzed. Median age was 49 years (IQR, 42-56 years). 47 patients (25.4%) were initially diagnosed with de novo stage IV disease. Visceral metastases were found in 95 patients (51.4%). The median PFS1 was 3.9 months (without anti-HER2 therapy) versus 15.6 months (with anti-HER2 therapy) between two groups (P&amp;lt; 0.001). Likewise, the median OS was significantly improved in anti-HER2 therapy group (34.0 months vs. 70.5 months, P=0.010). As a result of confirming the difference in OS according to the type of anti-HER2 therapies during the entire period of treatment by correspondence analysis, significant improvement was found when two or three types of anti-HER2 were used (without anti-HER2 vs. 2 types of anti-HER2, P=0.009; without anti-HER2 vs. 3 types of anti-HER2, P=0.010). Interestingly, when analyzed by treatment regimen, trastuzumab (H) + pertuzumab (P), HP + TDM-1, and H + TDM-1 significantly improved OS over regimens without anti-HER2 (without anti-HER2 vs. HP, P=0.009; without anti-HER2 vs. HP + TDM-1, P=0.013; without anti-HER2 vs. H + TDM-1, P=0.028, respectively). HP + TDM-1 therapies significantly improved survival rate compared to H single containing regimen (P=0.029). Based on our multiple Cox regression model, visceral metastasis was a significant poor OS prognostic factor and two and three types of anti-HER2 therapies were associated better OS prognosis (visceral metastasis: HR=2.40, P=0.003; 2 types of ant-HER2: HR=0.29, P=0.001; 3 types of anti-HER2: HR=0.22, P=0.018, respectively). Conclusions: Anti-HER2 therapies significantly improved PFS1 and OS. Continuing treatment by changing anti-HER2 therapies may act as a better prognostic factor. Further prospective studies are required. Citation Format: Ahrong Ham, Sewon Lee, Jungmin Jo, Soo Ji Hong, Ji Eun Lee, Haena Lee, Sungchan Gwark, Jeongshin An, Hyun-Goo Kim, Jun Woo Lee, Joohyun Woo, Woosung Lim, Byung-In Moon, Sei Hyun Ahn, Hye Ah Lee, Kyoung Eun Lee. Analysis of clinical benefit in the real world of HER2-positive metastatic breast cancer following the development of anti-HER2 therapeutics over the past 20 years [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-17-02.

The therapeutic effect and targets of herba Sarcandrae on breast cancer and the construction of a prognostic signature consisting of inflammation-related genes

BackgroundThe prevalence of breast cancer (BRCA), which is common among women, is on the rise. This study applied network pharmacology to explore the potential mechanism of action of herba sarcandrae in BRCA and construct a prognostic signature composed of inflammation-related genes. MethodsThe active ingredients of herba sarcandrae were screened using the SymMap, TCMID, and TCMSP platforms, and the molecular targets were determined in the UniProt database. The “drug-active compound-potential target” network was established with Cytoscape 3.7.2. The molecular targets were subjected to disease ontology, gene ontology (GO), and Kyoto Encyclopedia of Genes (KEGG) analyses. AutoDock software was used for molecular docking. Differentially expressed genes (DEGs) related to inflammation were obtained from the BRCA Cancer Genome Atlas (TCGA) database. In the training cohort, the univariate Cox regression model was applied to preliminarily screen prognostic genes. A multigene signature was built by the least absolute shrinkage and selection operator (LASSO) regression model, followed by validation through Kaplan‒Meier, Cox, and receiver operating characteristic (ROC) analyses. ResultsForty-one active compounds were identified, and 265 therapeutic targets for herba sarcandrae were predicted. GO enrichment results revealed significant enrichment of biological processes, such as response to xenobiotic stimuli, response to nutrient levels, and response to lipopolysaccharide. KEGG analysis revealed significant enrichment of pathways such as AGE-RAGE and chemical carcinogenesis receptor activation signaling pathways. In addition, the herbs Marc-Andre and rutin were shown to mediate BRCA cell proliferation and apoptosis via the interferon regulatory factor 1 (IRF1)/signal transducer and activator of transcription 3 (STAT3)/programmed death-ligand 1 (PD-L1) pathway. Sixteen inflammatory signatures, including BST2, GPR132, IL12B, IL18, IL1R1, IL2RB, IRF1, and others, were constructed, and the risk score was found to be a strong independent prognostic factor for overall survival in BRCA patients. The 16-inflammation signature was associated with several clinical features (age, clinical stage, T, and N classifications) and could reflect immune cell infiltration in tumor microenvironments with different immune cells. ConclusionsHerba sarcandrae and rutin were shown to mediate BRCA cell proliferation and apoptosis via the IRF1/STAT3/PD-L1 pathway, and the 16-member inflammatory signature might be a novel biomarker for predicting BRCA patient prognosis, providing more accurate guidance for clinical treatment prognosis evaluation and having important reference value for individualized treatment selection.

Prognostic factors and novel prediction models for overall survival of patients with submandibular gland cancer: A population-based retrospective cohort study

BackgroundAccurately predicting the survival rate of submandibular gland cancer (SGC) is of significant importance for guiding treatment decision-making and improving patient outcomes. This study was aimed to identify the independent prognostic factors of overall survival (OS) in SGC patients, and develop novel prediction models to aid clinicians in predicting the survival probability. Materials and methodsPatients diagnosed with primary SGC after the year 2010 were extracted from SEER database and then randomly allocated into training and test samples in a 7:3 ratio. Uni- and multi-variable COX analyses were employed using the training sample to ascertain independent prognostic factors for OS. Subsequently, graphic and online dynamic nomograms were established basing on the independent prognostic factors. We utilized C-index, calibration curve, receiver operating characteristic (ROC) curve, and area under ROC curve (AUC) value to evaluate the discrimination capacity and the consistency between predicted and actual survival. ResultsA total of 527 SGC patients were included (369 assigned to training group and 158 assigned to test group). The multivariable COX analysis showed that age, sex, marital status, tumor histology, summary stage, metastases to bone, and tumor size were independently associated with OS. Novel graphical and online dynamic (URL: https://yangxg1209.shinyapps.io/overall_survival_submandibular_gland_tumor/) nomograms were established. The C-indices (training: 0.77, 95%CI 0.71–0.84; test: 0.77, 95%CI 0.68–0.85) indicate favorable discrimination ability of the model, and the calibration curves demonstrated favorable consistency between the predicted and actual survival rates. ConclusionsOur study identified the independent prognostic factors influencing OS in patients with SGC, and successfully established and validated novel nomograms, which provide accurate prediction of survival rates and allows for personalized risk assessment.

Aspartate Transaminase-to-Albumin Ratio (ATAR), a Novel Prognostic Index, Predicts Outcomes in Patients with Small-Cell Lung Cancer.

Small cell lung cancer (SCLC) is characterized by high invasion rates, rapid progression, and poor prognoses. Thus, identifying SCLC patients at high risk of progression and death is critical to improve long-term survival. In this study, the aspartate transaminase-to-albumin ratio (ATAR) was examined as a prognostic factor for SCLC patients. We screened 196 SCLC patients from December 2013 to September 2022 at the Sichuan Cancer Hospital. The data was collected from patients' medical information as well as from their blood results during diagnosis. Using the Youden index as a cutoff value, patients were divided into high-risk（> 0.54) and low-risk (≤ 0.54) ATAR groups. We analyzed the prognostic factors for overall survival (OS) using the Kaplan-Meier method, univariate and multivariate analyses, Cox regression, and the C-index. There were 109 (55.6%) smokers among the patients, and the median OS was 17.55 months. The Kaplan-Meier analysis indicated that patients with high-risk ATAR had significantly lower OS (p < 0.0001). A multivariate analysis demonstrated that elevated ATAR is an independent adverse predictor of OS (p < 0.001, HR = 1.907). Our study found that ATAR is an independent predictor of survival outcomes in SCLC, which was superior to ALB, PNI, and SII in predicting outcomes in low-risk and high-risk groups (all p < 0.05). Models combining ATAR with ALB, PNI, and SII showed more powerful prognostic value than their corresponding original models. Moreover, the prognostic indicator ATAR can significantly stratify stage I - II and III - IV SCLC patients (p ＜ 0.05). Peripheral blood ATAR prognostic index can be used as an independent predictor of SCLC patients before treatment.

Keratin 6A is expressed at the invasive front and enhances the progression of colorectal cancer.

Keratins are intermediate filament proteins in epithelial cells, and they are important for cytoskeletal organization. Keratin 6A (KRT6A), classified as a type II keratin, is normally expressed in stratified squamous epithelium and squamous cell carcinomas. Little is known about the expression and role of KRT6A in adenocarcinomas. We investigated the clinicopathological and molecular biological significance of KRT6A in colorectal adenocarcinoma. Immunostaining of our institution's colorectal adenocarcinoma cases demonstrated that KRT6A showed significantly stronger expression at the invasive front than the tumor center (p < 0.0001). The high-KRT6A-expression cases (n = 47) tended to have a high budding grade associated with significantly worse prognoses. A multivariate analysis revealed that the KRT6A expression status was an independent prognostic factor for overall survival (p = 0.0004), disease-specific survival (p = 0.0097) and progression-free survival (p = 0.0033). The correlation between KRT6A and patient prognoses was also validated in an external cohort from a published dataset. To determine the function of KRT6A in vitro, KRT6A was over-expressed in three colon cancer cell lines, DLD-1, SW620, and HCT 116. KRT6A overexpression increased migration and invasion in DLD-1, but did not in SW620 and HCT116. In three-dimensional sphere-forming culture, KRT6A expression enhanced the irregular protrusion around the spheroid in DLD-1. Our findings in the present study indicated that KRT6A expression is a valuable prognostic marker of colorectal cancer and KRT6A may be involved the molecular mechanism in the progression of invasive areas of colorectal cancer.

Comparative analysis of liver resection in Non-B Non-C and hepatitis virus-associated hepatocellular carcinoma

BackgroundThe incidence of non-hepatitis B and non-hepatitis C hepatocellular carcinoma (NBNC-HCC) is increasing in our country. This study assesses the feasibility of employing an identical surgical treatment strategy for resectable NBNC-HCC as that for hepatitis virus-associated HCC (HV-HCC). MethodsA retrospective analysis (1993–2023) of 1321 curative liver resections for HCC at a single institution was performed. Propensity score matching ensured a balanced comparison of preoperative clinical factors, including tumor status and background liver condition. ResultsThe proportion of NBNC-HCC cases has gradually increased, reaching up to 70 %. After matching, 294 of 473 NBNC-HCC patients and 294 of 848 HV-HCC patients were compared. Operative outcomes, including operation time, blood loss, type of surgical procedure, and morbidity, were comparable. Long-term outcome analysis showed similar recurrence-free survival (HR: 0.86, 95 % CI: 0.70–1.06, P = 0.167) and overall survival (HR: 0.98, 95 % CI: 0.79–1.23, P = 0.865) for NBNC-HCC. Multivariable analysis identified ICGR15 ≥ 15 %, ALBI grade 2 or 3, aspartate aminotransferase ≥40, tumor size > 5 cm, multiple tumors, macrovascular invasion, and microvascular invasion as independent prognostic factors for overall survival, while hepatitis B or C virus status lost significance. ConclusionsDespite the increasing incidence of NBNC-HCC, comparable outcomes were achieved between the two groups of matched cohort.

The Prognostic Immune and Nutritional Indices Are Independent Prognostic Factors for Esophageal Cancer Patients Who Receive Curative Treatment.

Recently, the prognostic immune and nutritional index (PINI) was developed and reported to be a promising nutritional and inflammatory prognostic marker. The aim of the present study was to clarify the clinical impact of the PINI for esophageal cancer patients who received curative treatment. We conducted a retrospective review of medical records and collected data on consecutive esophageal cancer patients who underwent curative resection at Yokohama City University between 2005 and 2020. The PINI was calculated by dividing the serum ALB concentration (g/dl) by the serum monocyte concentration, both of which were measured before surgery. A total of 180 patients were included in this study. The cutoff value of the PINI was 3.0 in the present study. The 3- and 5-year overall survival rates were 45.2% and 33.5%, respectively, in the PINI-low subgroup, and 69.1% and 61.8%, respectively, in the PINI-high subgroup. A multivariate analysis demonstrated that the PINI was an independent prognostic factor for overall survival (hazard ratio=2.091, 95% confidence interval=1.287-3.399, p=0.003). Similar results were observed for recurrence-free survival. When comparing the sites of recurrence between the two groups, the incidence of hematological recurrence was significantly greater in the PINI-low subgroup compared to the PINI-high subgroup (46.8% vs. 21.1%, p<0.001). The PINI is a promising nutritional and inflammatory marker for esophageal cancer patients. The PINI might be a useful marker for the treatment and management of esophageal cancer patients.

Comparison of Survival Outcomes between Radical Antegrade Modular Pancreatosplenectomy and Conventional Distal Pancreatosplenectomy for Pancreatic Body and Tail Cancer: Korean Multicenter Propensity Score Match Analysis.

(1) Background: The aim of this study was to compare the survival benefit of radical antegrade modular pancreatosplenectomy (RAMPS) with conventional distal pancreatosplenectomy (cDPS) in left-sided pancreatic cancer. (2) Methods: A retrospective propensity score matching (PSM) analysis was conducted on 333 patients who underwent RAMPS or cDPS for left-sided pancreatic cancer at four tertiary cancer centers. The study assessed prognostic factors and compared survival and operative outcomes. (3) Results: After PSM, 99 patients were matched in each group. RAMPS resulted in a higher retrieved lymph node count than cDPS (15.0 vs. 10.0, p < 0.001). No significant differences were observed between the two groups in terms of R0 resection rate, blood loss, hospital stay, or morbidity. The 5-year overall survival rate was similar in both groups (cDPS vs. RAMPS, 44.4% vs. 45.2%, p = 0.853), and disease-free survival was also comparable. Multivariate analysis revealed that ASA score, preoperative CA19-9, histologic differentiation, R1 resection, adjuvant treatment, and lymphovascular invasion were significant prognostic factors for overall survival. Preoperative CA19-9, histologic differentiation, T-stage, adjuvant treatment, and lymphovascular invasion were independent significant prognostic factors for disease-free survival. (4) Conclusions: Although RAMPS resulted in a higher retrieved lymph node count, survival outcomes were not different between the two groups. RAMPS was a surgical option to achieve R0 resection rather than a standard procedure.

Genomic Landscape and Clinical Features of Advanced Thyroid Carcinoma: A National Database Study in Japan

Abstract Context The relationship between the genomic profile and prognosis of advanced thyroid carcinoma requiring drug therapy has not been reported. Objective To evaluate the treatment period and overall survival time for each genetic alteration in advanced thyroid carcinoma that requires drug therapy. Methods We conducted a retrospective observational study using a national database in Japan, which included 552 cases of thyroid carcinoma out of 53 543 patients in the database. Results The database included anaplastic thyroid carcinoma (23.6%), poorly differentiated thyroid carcinoma (10.0%), and differentiated thyroid carcinoma (66.4%). The most common genetic abnormalities were TERT promoter (66.3%), BRAF (56.7%), and TP53 (32.2%). The typical driver genes were BRAF V600E (55.0%), RAS (18.5%), RET fusion (4.7%), NTRK fusion (1.6%), and ALK fusion (0.4%). The most common regimen was lenvatinib, and the time to treatment failure was not different despite the presence of BRAF or RAS mutations. In differentiated thyroid carcinoma and poorly differentiated thyroid carcinoma, TP53 alterations independently predicted worse overall survival (hazard ratio = 2.205, 95% confidence interval: 1.135-4.283). In anaplastic thyroid carcinoma, no genetic alterations were associated with overall survival. Conclusion Genetic abnormalities with treatment options were found in 62.7% of advanced thyroid carcinomas. TP53 abnormality was an independent poor prognostic factor for overall survival in differentiated thyroid carcinoma. The time to treatment failure for lenvatinib was not different based on genetic profile.

Adjuvant chemotherapy in stage 1 colon cancer: Patient characteristics and survival analysis from the national cancer database

BackgroundA subset of patients in ACS-NCDB with stage-1 colon cancer received adjuvant chemotherapy (AC), in contrast to national guidelines. This study aimed to define this population and evaluate associations between AC and survival. MethodsPatients with T1-2N0 colon cancer from 2004 to 2016 were separated into AC and non-AC groups. Adverse pathological features (APF) included T2, poor differentiation, lymphovascular invasion, positive margin, and inadequate lymph nodes (<12). Cox proportional hazard models were used to estimate prognostic factors for overall survival (OS). ResultsA total of 1745 of 139,857 patients (1.2 %) received AC. Receiving AC was associated with male sex (p = 0.02), uninsured (p < 0.01), low income (p = 0.02), or having ≥2 APFs (p < 0.001). In the total cohort, AC was associated with increased mortality (HR 1.14 [1.04–1.24] P < 0.01). On subset analysis, AC was associated with improved OS for patients with ≥2 APFs (log-rank P=<0.001), and decreased mortality when adjusted for covariates (HR 0.81 [0.69–0.95] P=<0.01). The most significant predictor of mortality was old age (HR 3.78 [3.67, 3.89] p ≤ 0.01), followed by higher Charlson Comorbidity Index (HR 1.73 [1.69, 1.76] (p ≤ 0.01), and higher APF score (HR 1.46 [1.42, 15.2] p ≤ 0.01). ConclusionAC was associated with decreased survival in the total cohort of stage 1 colon cancer patients, but was associated with improved survival for patients with multiple APFs.

Retrospective Long-Term Evaluation of Conventional Transarterial Chemoembolization for Hepatocellular Carcinoma over 20 Years.

The aim of this study was to retrospectively evaluate the effects of conventional transarterial chemoembolization (cTACE) for the treatment of hepatocellular carcinoma over 20 years regarding overall survival (OS) and prognostic factors for OS. During the period from 1996 to 2016, 836 patients with HCC were treated with cTACE. Data evaluation was performed on the basis of pre- and postinterventional MRI and CT scans. Survival analysis was performed by Kaplan-Meier estimator; prognostic factors were determined by the use of Cox regression analysis. Overall, 4084 (mean 4.89 TACE sessions/patient) procedures were assessed. Median OS was 700 days (99% CI, 632.8-767.2). Depending on the indication, patients treated with a neoadjuvant intention showed the best OS (1229 days, 99% CI 983.8-1474.2) followed by curative intention (787 days, 99% CI 696.3-877.7), and then palliative intention (360 days, 99% CI 328.4-391.6). Portal vein thrombosis (HR 2.19, CI 1.63-2.96, and p < 0.01) and Child-Pugh class B or worse (HR 1.44, CI 1.11-1.86, and p < 0.001) were significantly associated with shorter OS. Patients with HCC benefit from TACE after careful patient selection. Portal vein thrombosis and Child-Pugh class B or worse are significantly unfavorable prognostic factors for patients' survival.

Predictive value of 18F-FDG PET/CT versus bone marrow biopsy and aspiration in pediatric neuroblastoma.

Neuroblastoma (NB) is the most prevalent solid extracranial malignancy in children, often with bone marrow metastases (BMM) are present. The conventional approach for detecting BMM is bone marrow biopsy and aspiration (BMBA). 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) has become a staple for staging and is also capable of evaluating marrow infiltration. The consensus on the utility of 18F-FDG PET/CT for assessing BMM in NB patients is still under deliberation. This retrospective study enrolled 266 pediatric patients with pathologically proven NB. All patients had pretherapy FDG PET/CT. BMBA, clinical, radiological, and follow-up data were also collected. The diagnostic accuracy of BMBA and 18F-FDG PET/CT was assessed. BMBAs identified BMM in 96 cases (36.1%), while 18F-FDG PET/CT detected BMI in 106 cases (39.8%) within the cohort. The initial sensitivity, positive predictive value (PPV), specificity, and negative predictive value (NPV) of 18F-FDG PET/CT were 93.8%, 84.9%, 90.6%, and 96.3%, respectively. After treatment, these values were 92.3%, 70.6%, 97.3%, and 99.4%, respectively. The kappa statistic, which measures agreement between BMBA and 18F-FDG PET/CT, was 0.825 before treatment and 0.784 after treatment, with both values indicating a substantial agreement (P = 0.000). Additionally, the amplification of MYCN and a positive initial PET/CT scan were identified as independent prognostic factors for overall survival (OS). 18F-FDG-PET/CT is a valuable method for evaluating BMM in NB. The routine practice of performing a BMBA without discrimination may need to be reassessed. Negative result from 18F-FDG-PET/CT could potentially spare children with invasive bone marrow biopsies.

Prognostic factors for resected cases with gallbladder carcinoma: A systematic review and meta-analysis.

Current meta-analysis was performed to systematically evaluate the potential prognostic factors for overall survival (OS) among resected cases with gallbladder carcinoma (GBC). PubMed, EMBASE, and the Cochrane Library were systematically retrieved and hazard ratio (HR) and its 95% confidence interval (CI) were directly extracted from the original study or roughly estimated via Tierney's method. Standard Parmar modifications were used to determine pooled HRs. A total of 36 studies with 11502 cases were identified. Pooled results of univariate analyses indicated that advanced age (HR=1.02, P=0.00020), concurrent gallstone disease (HR=1.22, P=0.00200), elevated preoperative CA199 level (HR=1.93, P<0.00001), advanced T stage (HR=3.09, P<0.00001), lymph node metastasis (HR=2.78, P<0.00001), peri-neural invasion (HR=2.20, P<0.00001), lymph-vascular invasion (HR=2.37, P<0.00001), vascular invasion (HR=2.28, P<0.00001), poorly differentiated tumor (HR=3.22, P<0.00001), hepatic side tumor (HR=1.85, P<0.00001), proximal tumor (neck/cystic duct) (HR=1.78, P<0.00001), combined bile duct resection (HR=1.45, P<0.00001), and positive surgical margin (HR=2.90, P<0.00001) were well-established prognostic factors. Pathological subtypes (P=0.53000) and postoperative adjuvant chemotherapy (P=0.70000) were not prognostic factors. Pooled results of multi-variate analyses indicated that age, gallstone disease, preoperative CA199, T stage, lymph node metastasis, peri-neural invasion, lymph-vascular invasion, tumor differentiation status, tumor location (peritoneal side vs hepatic side), surgical margin, combined bile duct resection, and postoperative adjuvant chemotherapy were independent prognostic factors. Various prognostic factors have been identified beyond the 8th AJCC staging system. By incorporating these factors into a prognostic model, a more individualized prognostication and treatment regime would be developed. Upcoming multinational studies are required for the further refine and validation.

Impact of preoperative haemoglobin, albumin, lymphocyte, and platelet score on oral cancer prognosis.

To evaluate the preoperative haemoglobin, albumin, lymphocyte, and platelet score as a prognostic indicator in oral squamous cell carcinoma treated by radical surgery. Patients (83 men, 32 women; 65.80 ± 11.47 years) who underwent radical surgery between 2012 and 2022 were included. Factors affecting overall survival and disease-free survival according to the haemoglobin, albumin, lymphocyte, and platelet score were examined. Patients were categorised into low- and high-score groups using optimal cut-off values obtained from receiver operating characteristic curve analysis. The low-score group had poorer overall and disease-free survival (p < 0.001 each). Multivariate analysis identified alcohol consumption (hazard ratio [HR], 3.83; 95% confidence interval [CI]: 1.56-9.41, p = 0.003); vascular invasion (HR, 3.97; 95% CI: 1.60-9.85, p = 0.003); and the haemoglobin, albumin, lymphocyte, and platelet score (HR, 0.39; 95% CI: 0.20-0.78, p = 0.007) as independent prognostic factors for overall survival and vascular (HR, 3.66; 95% CI: 1.79-7.50, p < 0.001) and lymphovascular (HR, 2.44; 95% CI: 1.36-4.41, p = 0.003) invasion as independent prognostic factors for disease-free survival. The preoperative haemoglobin, albumin, lymphocyte, and platelet score may be a significant prognostic factor for patients with oral squamous cell carcinoma undergoing radical surgery.