Poor Prognostic Factor For Overall Survival Research Articles

Unleashing the potential: transarterial chemoembolization combined with intra-arterial infusion of bevacizumab for unresectable hepatocellular carcinoma.

The purpose of this study is to compare the efficacy and safety of transarterial chemoembolization (TACE) alone with transarterial chemoembolization combined with the arterial infusion of bevacizumab (TACE + Bev) in patients with unresectable hepatocellular carcinoma (uHCC). A retrospective analysis was conducted on 446 uHCC patients treated with TACE or TACE + Bev between January 2021 and March 2023. The study evaluated objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events in both treatment groups. Finally, the TACE group comprised 295 patients, and the TACE + Bev group comprised 151 patients. Patients in the TACE + Bev group exhibited significantly prolonged median PFS (7.9months vs. 10.3months, P = 0.013) and median OS (16.1months vs. 21.4months, P = 0.041), improved ORR (26.8% vs. 37.7%, P = 0.017) and DCR (71.5% vs. 80.8%, P = 0.033) compared to the TACE group. Multifactorial Cox analysis identified alpha-fetoprotein (AFP) > 400ng/ml as an independent prognostic factor for PFS and OS. Meanwhile, portal vein cancer thrombosis and distant metastasis are poor prognostic factors for OS. The overall incidence of adverse events was similar between the two groups. In comparison with the TACE group, the TACE + Bev group demonstrated efficacy in improving outcomes for patients with uHCC with a manageable safety profile.

Prognostic Impact of Squamous Cell Carcinoma Antigen During Neoadjuvant Chemotherapy for Patients With Esophageal Squamous Cell Carcinoma Treated With Minimally Invasive Esophagectomy.

Squamous cell carcinoma antigen (SCC) is widely used as a tumor marker for esophageal cancer. In this study, we investigated the relationship between SCC and long-term outcomes in patients with esophageal squamous cell carcinoma after neoadjuvant chemotherapy (NAC) followed by minimally invasive esophagectomy (MIE). Between 2010 and 2018, 124 patients with ESCC who underwent MIE after NAC (cisplatin plus 5-fluorouracil) were included. Patients were divided into low and high groups based on their pre-NAC SCC level, according to the cut-off value determined using a receiver operating characteristic curve. These two patient groups were further divided into subgroups by receiver operating characteristics according to whether SCC was low or high after NAC. For overall survival (OS), the cut-off value for SCC pre-NAC was 0.9 ng/ml. Ninety-six patients were in the high SCC group (≥0.9 ng/ml) and 28 patients were in the low SCC group (<0.9 ng/ml) prior to NAC. The patients were then divided into pre-NAC/post-NAC SCC subgroups accordingly: low/low SCC (n=7), low/high SCC (n=21), high/low SCC (n=53), and high/high SCC (n=43). The 5-year OS rates were 100%, 66.7%, 50.9%, and 32.6%, respectively. In the multivariate analysis for OS, a high/high pre-NAC/post-NAC SCC status was an independent prognostic factor for poorer OS, along with pathological N stage. For patients with esophageal squamous cell carcinoma treated with NAC followed by MIE, a high SCC level prior to NAC which was also high after NAC was an independent prognostic factor and might contribute to deciding the need for adjuvant therapy.

Chronological evolution in liver resection for hepatocellular carcinoma: Prognostic trends across three decades in early to advanced stages

BackgroundWhile liver resection remains the best curative option for hepatocellular carcinoma (HCC), it is unclear whether the consistent progress of multidisciplinary approaches in managing HCC over several decades has influenced the outcomes of liver resection. MethodsPatients undergoing liver resection for HCC from 1993 to 2022 in our institution were retrospectively assessed and stratified into three periods according to the year of liver resection, P1 (1993–2000), P2 (2001–2009), and P3 (2010–2022), and tumor status using the Barcelona Clinic Liver Cancer (BCLC) staging system. ResultsA total of 1257 patients were included (P1:P2:P3 = 385:490:382, BCLC stage 0/A:B:C = 908:214:135). In the entire cohort, long-term surgical outcomes significantly improved across the three periods. In BCLC stage 0/A HCC, the 5-year overall survival (OS) rate improved from P1 to P3 (P1: 65.5 %, P2: 71.3 %, P3: 80.4 %), with HRs of 0.655 (95 % CI: 0.536 to 0.800) and 0.595 (95 % CI: 0.455 to 0.778) for P2 vs. P1 and P3 vs. P1, respectively. Conversely, limited advancements were observed in patients with BCLC stage B or C HCC. Multivariate analysis in BCLC stage 0/A patients demonstrated that ICGR15 > 15 %, ALBI grade 2 or 3 (vs. 1), multiple tumors, microvascular invasion, and surgical period (P2 vs.P1) remained independent poor prognostic factors for OS. ConclusionsSubstantial advancements in the long-term outcomes for HCC patients undergoing liver resection, particularly in BCLC stage 0/A, were observed, while minimal improvement was noted for BCLC stage B and C.

High Subcutaneous Adipose Tissue Radiodensity Predicts Poor Prognosis in Patients With Gastric Cancer.

Although the impact of body composition on cancer treatment outcomes of patients with cancer has been increasingly reported, it is still unclear whether the radiodensity of subcutaneous adipose tissue (SAT) on computed tomography (CT) images has a prognostic impact on patients with gastric cancer. We measured muscle and SAT profiles on CT and performed an integrated analysis with clinicopathologic factors. We retrospectively analyzed 230 patients with gastric cancer who underwent gastrectomy between June 2016 and December 2020. SAT radiodensity (SAT-R), and skeletal muscle index (SMI) were measured in preoperative CT images. These were compared with clinicopathologic factors, overall survival (OS), and recurrence-free survival (RFS). High SAT-R was significantly associated with older age (p=0.003) and lower BMI, lymphocyte, hemoglobin, γ-GTP, cholinesterase, albumin, and triglyceride values (p<0.001, <0.001, 0.027, 0.032, <0.001, 0.001, and <0.001, respectively). In the univariate analysis, high SAT-R, and low SMI were significantly associated with poor OS (p=0.003 and <0.001) and poor RFS (p=0.014 and 0.011). In the multivariate analysis by Cox proportional hazard model, high SAT-R and low SMI were identified as independent prognostic factors for poor OS (p=0.037 and 0.007). High SAT-R on preoperative CT was associated with poor OS in patients with gastric cancer after gastrectomy. SAT-R has a potential to be a novel prognostic marker for surgically treated patients with gastric cancer.

Prognostic relevance of sarcopenia and tumor‐infiltrating CD8+ T cells in patients with hepatocellular carcinoma

AbstractAimThe relationship between sarcopenia, tumor‐infiltrating lymphocytes (TILs), and long‐term survival in patients with hepatocellular carcinoma (HCC) has not been investigated. We aimed to evaluate the prognostic relevance of sarcopenia and TILs in patients with HCC.MethodsWe included 351 patients with HCC following liver resection. Sarcopenia was defined based on the skeletal muscle index using computed tomography. Tumor‐infiltrating CD4+ and CD8+ T cells, perforin, and granzyme B were examined in liver resection specimens.ResultsSarcopenia patients had a significantly lower lymphocyte count (p = 0.003), prognostic nutritional index (p = 0.017), and CD4+ and CD8+ T cell counts (p = 0.008 and p = 0.006, respectively). The overall survival (OS) and recurrence‐free survival (RFS) rates of sarcopenia patients were significantly lower than non‐sarcopenia patients (both p &lt; 0.001). Multivariate analysis revealed that sarcopenia and low CD8 levels were strong independent poor prognostic factors for OS and RFS (both p &lt; 0.001). Regardless of sarcopenia, patients with high CD8 levels had significantly better OS and RFS rates and increased expression of perforin and granzyme B. Particularly, sarcopenia patients with high CD8 levels had much better OS and RFS than those with low CD8 levels and were even comparable to non‐sarcopenia patients with high CD8 levels.ConclusionsSarcopenia and low CD8 levels are strong independent poor prognostic factors in patients with HCC. Furthermore, sarcopenia patients with high CD8 levels had favorable survival and activated local immunity, suggesting that tumor‐infiltrating CD8+ T cells may play a functionally important role in sarcopenia patients.

Efficacy of immune checkpoint inhibitors according to programmed cell death-ligand 1 expression in patients with non-small cell lung cancer and brain metastasis: A real-world prospective observational study.

Studies have shown the antitumor efficacy of immune checkpoint inhibitors (ICI) in patients with non-small cell lung cancer (NSCLC) and brain metastases (BM). However, it is unclear whether the efficacy of ICI is similar between patients with and without BM. It is yet unclear whether the efficacy of ICI in patients with BM increases with higher levels of programmed cell death-ligand 1 (PD-L1) expression, as observed in patients without BM. We compared the outcomes of ICI treatment between patients with and without BM using a cohort containing 1741 prospectively enrolled patients with lung cancer. We investigated whether there were differences in the outcomes of ICI based on PD-L1 expression levels between these patients. We enrolled 240 patients with NSCLC with or without BM who were treated with ICI or both chemotherapy and ICI. There were no significant differences in overall survival (OS) between all patients with or without BM (p = 0.489). However, OS was significantly shorter in patients with BM than in those without in the PD-L1 ≥ 50% group (16.5 M vs. 30.6 M, p = 0.003) but not in the PD-L1 ≥ 1% or negative group. BM was an independent poor prognostic factor for OS (hazard ratio: [95% confidence interval], 2.045; [1.058-3.953], p = 0.033) in the PD-L1 ≥ 50% group. Our study indicated that the outcomes of patients with or without BM treated with ICI were not significantly different. The efficacy of ICI in patients with PD-L1 expression ≥50% would be lower in patients with BM than in those without.

Population-Based Cohort Study on Treatment and Overall Survival of Patients Clinically Diagnosed With T1 Ampullary Cancer.

To evaluate treatment outcomes, overall survival (OS), and prognostic factors for OS in patients diagnosed with T1 ampullary cancer. Ampullary cancer is a rare gastrointestinal malignancy with limited data from large cohorts, especially regarding T1 disease. Patients diagnosed with clinical (c) T1 ampullary cancer and patients with pathological (p) T1 in the case of cTx were included from the Netherlands Cancer Registry (2014-2021). Primary endpoint was OS, analyzed using the Kaplan-Meier estimator. Multivariable Cox proportional hazards regression was used to identify OS predictors. Overall, 244 patients with cT1 ampullary cancer were included, of whom 75% (n=184) underwent resection. Among these, 68% (n=125) were upstaged to a higher pathologically T classification (pT2:40%, pT3:22%, pT4:5%). Similarly, cN0 was upstaged to pN1 in 47% of patients (n=87). Next, 100 patients with pT1 and cTx ampullary cancer were included, making a total of 159 patients with pT1 tumor. 92% (146/159) underwent pancreatoduodenectomy while 8% (13/159) underwent endoscopic or local surgical resection. The 1- and 5-year OS for cT1N0 ampullary cancer were 72% and 36%, while for pT1N0 they were 94% and 75%. Independent poor prognostic factors for OS were pN1 classification (HR 2.12; 95%CI 1.15-3.94, P=0.017), pNx classification (i.e. locally resected patients) (HR 2.82; 95%CI 1.22-6.55, P=0.016), and poorly differentiated tumors (HR 4.05; 95%CI 1.33-12.40, P=0.014). In patients with cT1 ampullary cancer, more than two-thirds had a pathologically higher T classification, and almost half had a pathologically higher N classification. These findings suggest that pancreatoduodenectomy is recommended for cT1 ampullary cancer.

Evaluating the impact of treatment sequencing on outcomes in hepatocellular carcinoma: a comparative analysis of TACE and systemic therapies

This study aimed to evaluate how the timing of transarterial chemoembolization (TACE) relative to systemic therapy (tyrosine-kinase inhibitors [TKIs] and immune checkpoint inhibitors [ICIs]) influences oncological outcomes in patients with hepatocellular carcinoma (HCC). A retrospective analysis was conducted on HCC patients treated with TACE plus TKIs and ICIs from January 2018 to February 2023. We compared objective response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) between patients receiving TACE before versus after systemic therapies. Multivariate Cox regression analyses identified potential prognostic factors. Of the 194 patients enrolled, 111 received TACE before systemic therapies, and 83 after. The median age at diagnosis was 52.8 years. There were no significant differences in ORR (40.72% vs. 30.41%, p = 0.989) or DCR (48.45% vs. 35.57%, p = 0.770) between the groups. Likewise, OS (18.73 vs. 18.20 months, p = 0.091) and PFS (11.53 vs. 10.05 months, p = 0.336) were similar regardless of treatment sequence. In the result of Cox analysis, a 20% decrease in AFP from baseline at one month was associated with improved OS (HR = 0.35, 95% CI 0.17–0.70, p = 0.003) and PFS (HR = 0.69, 95% CI 0.49–0.96, p = 0.028). Large tumor size (≥ 10 cm) was a poor prognostic factor for OS (HR = 2.12, 95% CI 1.07–4.21, p = 0.032), and the presence of portal vein tumor thrombus adversely affected PFS (HR = 2.31, 95% CI 1.47–3.62, p < 0.001). The sequencing of TACE and systemic therapies does not significantly impact the prognosis of advanced HCC. A 20% reduction in AFP within one month of treatment commencement emerges as a protective prognostic factor for HCC.Graphical

Persistent acute kidney injury: Postoperative impact and predictors in patients undergoing liver resection.

Persistent acute kidney injury (AKI) has not been investigated in patients undergoing liver resection. We aimed to identify the predictors of persistent AKI, its effect on postoperative outcomes and long-term renal function in patients following liver resection, and its impact on survival in patients with hepatocellular carcinoma (HCC). We examined 990 patients who underwent liver resection, including a subgroup analysis of 384 patients with curative resection for initial HCC. Persistent AKI was defined as residual impairment of serum creatinine≥0.3mg/dL or≥50% from baseline 1month after surgery. The persistent AKI group had significantly worse postoperative outcomes, including overall morbidity, major morbidity, longer hospital stay, and 90-day mortality. In the subgroup analysis of patients with HCC, persistent AKI was associated with a significantly poorer overall survival (OS) rate (p<0.001), and the multivariate analysis confirmed persistent AKI as an independent poor prognostic factor for OS (p=0.005). The long-term postoperative estimated glomerular filtration rate decline was significantly greater in the persistent AKI group than in the no AKI and transient AKI groups (p<0.001 for both). Chronic kidney disease, albumin-bilirubin grade ≥2, and anatomical resection were independent predictors of persistent AKI (p=0.001, p=0.039, and p=0.015, respectively). Persistent AKI adversely affects postoperative outcomes and long-term renal function in patients undergoing liver resection. Furthermore, it is associated with poor prognosis in patients with HCC. Therapeutic strategies to prevent persistent AKI are critical for improving postoperative outcomes in these patients.

Prognosis prediction of PDAC via detection of O-glycan altered extracellular vesicles in perioperative sera.

Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy due to the difficulty in diagnosis and poor prognosis because of the high recurrence rate, necessitating reliable biomarkers to improve the diagnosis and prognosis. However, the existing markers have limitations. We previously identified extracellular vesicles (EVs) recognized by O-glycan-binding lectins (Amaranthus caudatus agglutinin [ACA]) as a novel diagnostic biomarker for PDAC using an EV-counting system (ExoCounter). This retrospective study analyzed changes in ACA-positive EVs in perioperative PDAC serum and its association with prognosis using ExoCounter. Absolute EV levels in the pre- and postoperative sera of 44 patients who underwent curative pancreatectomy for PDAC were quantified using ExoCounter. The carbohydrate antigen 19-9 levels declined in most samples postoperatively, and presented no correlation with poor prognosis. In contrast, ACA-positive EVs increased in serum at 7 days postoperatively in 27 of 44 patients (61.4%). We therefore divided participants with ACA-positive EVs before and after surgery into elevation and decline groups. The overall survival (OS) and recurrence-free survival (RFS) of patients with higher ACA-positive EVs were significantly shorter than those with lower ACA-positive EVs (26.1 months vs. not reached, P = 0.018; 11.9 vs. 38.6 months, P = 0.013). Multivariable analysis revealed that ACA-positive EV elevation in postoperative serum was an independent prognostic factor for poor OS (hazard ratio [HR] = 3.891, P = 0.023) and RFS (HR = 2.650, P = 0.024). The detection of ACA-positive EVs in perioperative serum may be used to predict the prognosis of PDAC in the early postoperative period.

Chromosome 1q21 Aberrations Are Poor Prognostic Factors for Newly Diagnosed Multiple Myeloma Patients.

Chromosome 1q21 aberrations are one of the most common cytogenetic abnormalities in patients with multiple myeloma (MM). However, the prognostic value remains controversial. This study aimed to determine the prognostic value of numerical abnormalities of chromosome 1q21 for newly diagnosed patients with MM patients in Chinese population. We retrospectively analyzed 629 patients with newly diagnosed MM who received the detection of chromosome 1q21 by fluorescence insitu hybridization in China. Among 629 patients, 309 (49.1%) had 1q21 abnormalities, of which 187 (29.7%) had three copies and 122 (19.4%) had four or more copies. Patients with two copies of 1q21 had a significantly longer median overall survival (OS) than those with three copies or ≥4 copies and also had longer progression-free survival (PFS). However, patients with three or ≥4 copies had similar OS and PFS. Univariate Cox proportional hazards regression analyses determined that 1q21 aberrations are associated with shorter OS and PFS. 1q21 aberrations are also independent poor prognostic factors for OS and PFS in multivariable analyses. Del(17p), t(4;14), and t(14;16) are common high-risk cytogenetic abnormalities (HRCAs) in patients with MM. Patients with 1q21+ alone or 1q21+ combined with HRCAs had shorter OS and PFS than patients without cytogenetic abnormalities. Patients with 1q21+ and t(11;14) also had shorter PFS but had similar OS than patients without cytogenetic abnormalities. Our study showed that chromosome 1q21 aberrations are poor prognostic factors for newly diagnosed patients with MM.

Efficacy and prognostic factors of stereotactic body radiotherapy combined with immunotherapy for pulmonary oligometastases: a preliminary retrospective cohort study.

Stereotactic body radiotherapy (SBRT) combined immunotherapy has a synergistic effect on patients with stage IV tumors. However, the efficacy and prognostic factors analysis of SBRT combined immunotherapy for patients with pulmonary oligometastases have rarely been reported in the studies. The purpose of this study is to explore the efficacy and prognostic factors analysis of SBRT combined immunotherapy for patients with oligometastatic lung tumors. A retrospective analysis was conducted on 43 patients with advanced tumors who received SBRT combined with immunotherapy for pulmonary oligometastases from October 2018 to October 2021. Local control (LC), progression-free survival (PFS), and overall survival (OS) were assessed using the Kaplan-Meier method. Univariate and multivariate analyses of OS were performed using the Cox regression model, and the P value <0.05 was considered statistically significant. The receiver operating characteristic (ROC) curve of neutrophil-to-lymphocyte ratio (NLR) after SBRT was generated. Spearman correlation analysis was used to determine the relationship of planning target volume (PTV) with absolute lymphocyte count (ALC) before and after SBRT and with neutrophil count (NE) after SBRT. Additionally, linear regression was used to examine the relationship between ALC after SBRT and clinical factors. A total of 43 patients with pulmonary oligometastases receiving SBRT combined with immunotherapy were included in the study. The change in NLR after SBRT was statistically significant (P<0.001). At 1 and 2 years, respectively, the LC rates were 90.3% and 87.5%, the OS rates were 83.46% and 60.99%, and the PFS rates were 69.92% and 54.25%, with a median PFS of 27.00 (17.84-36.13) months. Univariate and multivariate Cox regression analyses showed that a shorter interval between radiotherapy and immunization [≤21 days; hazard ratio (HR) =1.10, 95% confidence interval (CI): 0.06-0.89; P=0.02] and a low NLR after SBRT (HR =0.24, 95% CI: 1.01-1.9; P=0.03) were associated with improved OS. The ROC curve identified 4.12 as the cutoff value for predicting OS based on NLR after SBRT. NLR after SBRT ≤4.12 significantly extended OS compared to NLR after SBRT >4.12 (log-rank P=0.001). Spearman correlation analysis and linear regression analysis showed that PTV was negatively correlated with ALC after SBRT. Our preliminary research shows that SBRT combined with immunotherapy has a good effect, and NLR after SBRT is a poor prognostic factor for OS. Larger PTV volume is associated with decreased ALC after SBRT.

High expression of HM13 correlates with poor prognosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has a high mortality rate, and the identification of early prognostic markers is crucial for improving patient outcomes. This study aimed to investigate the correlation between the expression of Histocompatibility Minor 13 (HM13) and the prognosis of HCC patients. HM13 protein expression was assessed in HCC tissues and cells through immunohistochemistry (IHC), quantitative reverse transcription PCR (qRT-PCR), and western blot. The relationship between HM13 expression and clinicopathological data of HCC was evaluated. Bioinformatics analyses, including Gene Expression Omnibus (GEO) database, Gene Expression Profiling Interactive Analysis (GEPIA), and Kaplan-Meier plotter (K-M plotter), were employed to analyze HM13 expression and its association with patient survival. HM13 was significantly overexpressed in HCC tissues and cells compared to normal controls. IHC revealed that HM13 protein was primarily localized in the cytoplasm and highly expressed in HCC tissues. Interestingly, patients with high HM13 expression had significantly poorer overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-specific survival (DSS) than those with low expression. HM13 expression was associated with Edmondson grade, metastasis, microvascular invasion, and alpha-fetoprotein (AFP) levels. Multivariate analysis identified HM13 as an independent prognostic factor for poor OS in HCC. HM13 was markedly overexpressed in HCC and correlated with poor prognosis, suggesting its potential as a promising biomarker for early prognostic detection in HCC patients.

Evaluation of preoperative visceral fat area / psoas muscle area ratio and prognosis in patients with colorectal cancer

AbstractBackgroundRecent research has focused on the prognostic relevance of preoperative sarcopenia and sarcopenic obesity in various cancers. In this study we investigated the relationship between visceral fat area (VFA), psoas muscle area (PMA), and the prognosis of patients undergoing colorectal cancer surgery.MethodsPatients with stage III colorectal cancer who underwent surgery between July 2013 and April 2020 were included. The analysis was performed on 151 patients who met the criteria. The VFA and PMA were measured at the level of the third lumbar vertebra on computed tomography (CT) scans, and the ratio of VFA to PMA (V/P ratio) was determined.ResultsPatients with high V/P ratios were significantly older (p = 0.0213), had a higher body mass index (BMI) (p &lt; 0.0001), a higher percentage of sarcopenic obesity (p &lt; 0.0001), and more diabetes complications (p &lt; 0.0001). Prognostic analysis showed that the overall survival (OS) (p = 0.0154) and relapse‐free survival (RFS) (p = 0.0378) were significantly worse in patients with a high V/P ratio. Multivariate analysis revealed that a high V/P ratio was an independent poor prognostic factor for OS. Subgroup analysis was then performed in patients with BMI &lt; 25 kg/m2. OS (p = 0.0259) and RFS (p = 0.0275) were significantly worse in the high V/P ratio group. A high V/P ratio was an independent poor prognostic factor in the multivariate analysis.ConclusionIn colorectal cancer, the preoperative V/P ratio is an independent factor for poor prognosis. Preoperative evaluation of the V/P ratio may identify a wide range of high‐risk patients because it is an independent poor prognostic factor in patients without obesity.

Prognostic significance of micronest in cancer stroma in resected lung squamous cell carcinoma

Tumor budding in the cancer stroma has been reported to be a prognostic factor in non-small cell lung cancer. Micronest in cancer stroma (MICS) is often observed as a formation that is larger and more conspicuous than budding, but its clinicopathologic significance is unclear. In this study, we aimed to examine the clinicopathological significance of MICS in lung squamous cell carcinoma (LSqCC).A total of 198 consecutive patients with pathologically diagnosed LSqCC (anyT N0-1M0) were enrolled in this study. MICS were defined as those that met the following criteria: (1) consisting of 5–200 tumor cells or less than 200 μm in diameter and (2) more than 200 μm away from the adjacent main lesion. The prognostic impact of the presence or absence of MICS and the characteristics of MICS-forming cancer cells were evaluated by immunohistochemistry (IHC).MICS was observed in 57 patients (28.8%), and overall survival (OS) and recurrence-free survival (RFS) were significantly shorter in the MICS-positive group (OS: 44.4% vs. 84.4%, p < 0.001; RFS: 30.0% vs. 82.6%, p < 0.001). Univariate and multivariate analyses revealed that the presence of MICS was an independent poor prognostic factor for OS (hazard ratio [HR] 3.54, p < 0.001) and RFS (HR 4.99, p < 0.001). Immunohistochemistry showed that the expression levels of the cell-cell adhesion molecule E-cadherin and hypoxia-induced protein GLUT-1 were significantly decreased in cancer cells forming MICS lesions compared to the tumor component excluding MICS within the same tumor (non-MICS lesions).Our data show that MICS is a distinct morphological feature with important biological and prognostic significance.

Effectiveness of immune checkpoint inhibitor therapy on bone metastases in non-small-cell lung cancer.

Bone metastases (BoMs) are prevalent in patients with metastatic non-small-cell lung cancer (NSCLC) however, there are limited data detailing how BoMs respond to immune checkpoint inhibitors (ICIs). The purpose of this study was to compare the imaging response to ICIs of BoMs against visceral metastases and to evaluate the effect of BoMs on survival. A retrospective, multicentre cohort study was conducted in patients with NSCLC treated with nivolumab or pembrolizumab in Alberta, Canada from 2015 to 2020. The primary endpoint was the real-world organ specific progression free survival (osPFS) of bone versus visceral metastases. Visceral metastases were categorized as adrenal, brain, liver, lung, lymph node, or other intra-abdominal lesions. The secondary outcome was overall survival (OS) amongst patients with and without BoMs. A total of 573 patients were included of which all patients had visceral metastases and 243 patients (42.4%) had BoMs. High PD-L1 expression was identified in 268 patients (46.8%). No significant difference in osPFS was observed between bone, liver, and intra-abdominal metastases (p=0.20 and p=0.76, respectively), with all showing shorter osPFS than other disease sites. There was no difference in the osPFS of extra-thoracic sites of disease in patients with high PD-L1 expression. There was significant discordance between visceral disease response and bone disease response to ICI (p=0.047). The presence of BoMs was an independent poor prognostic factor for OS (HR 1.26, 95%CI: 1.05-1.53, p=0.01). Metastatic bone, liver, and intra-abdominal lesions demonstrated inferior clinical responses to ICI relative to other sites of disease. Additionally, the presence of bone and liver metastases were independent poor prognostic factors for overall survival. This real-world data suggests that BoMs respond poorly to ICI and may require treatment adjuncts for disease control.

Circ_0012152 Accelerates Acute Myeloid Leukemia Progression through the miR-652-3p/SOX4 Axis.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy characterized by abnormal myeloid blast expansion. Recent studies have demonstrated that circular RNAs play a role in AML pathogenesis. In this study, we aimed to investigate the clinical significance of circ_0012152 in AML and elucidate its underlying molecular mechanism in the pathogenesis of this condition. Circ_0012152 expression was detected by quantitative real-time polymerase chain reaction in samples obtained from 247 patients with AML and 40 healthy controls. A systematic analysis of clinical characteristics and prognostic factors was also conducted. Cell growth was assessed using the Cell Counting Kit-8 (CCK-8) assay, and apoptosis and cell cycle progression were evaluated by flow cytometry. Moreover, RNA pull-down was performed to identify target microRNAs, and transcriptome RNA sequencing and bioinformatics analyses were utilized to identify downstream mRNA targets. Circ_0012152 was significantly upregulated in samples from patients with AML and served as an independent adverse prognostic factor for overall survival (OS) (hazard ratio: 2.357; 95% confidence interval 1.258-4.415). The circ_0012152 knockdown reduced cell growth, increased apoptosis, and inhibited cell cycle progression in AML cell lines. RNA pull-down and sequencing identified miR-652-3p as a target microRNA of circ_0012152. Cell growth inhibition by circ_0012152 knockdown was significantly relieved by miR-652-3p inhibitors. We suggested that miR-652-3p targeted SOX4, as the decrease in SOX4 expression resulting from circ_0012152 knockdown was upregulated by miR-652-3p inhibitors in AML cells. Circ_0012152 is an independent poor prognostic factor for OS in AML, and it promotes AML cell growth by upregulating SOX4 through miR-652-3p.

The efficacy of cumulative cisplatin dose on survival in patients with locally advanced cervical cancer treated with definitive chemoradiotherapy: A multicenter study by the Turkish Oncology Group (TOG).

e17534 Background: This multicentric study aimed to investigate the impact of cumulative cisplatin dose on clinical outcomes in locally advanced cervical cancer patients undergoing definitive chemoradiotherapy (CRT). Methods: A retrospective analysis was conducted on 654 patients with stage IB3-IVA disease treated with definitive CRT. Radiotherapy (RT) was applied as external beam pelvic with or without para-aortic RT and brachytherapy. Concomitant chemotherapy was in the form of weekly or 3-weekly cisplatin. Data on demographics, treatment protocols, cumulative cisplatin dose, adverse effects, and survival outcomes were collected. Statistical analyses, including univariate and multivariate Cox regression models, were employed to assess factors influencing progression-free survival (PFS) and overall survival (OS). Results: The median cumulative cisplatin dose was 210 mg (range, 40-320 mg), and it was ≥200 mg in 503 (76.9%) patients. Median follow-up was 35 months. The 5-year PFS and OS rates were 66.9% and 77.1%, respectively. Multivariate analysis (MVA) identified poor performance status, non-squamous cell histology, presence of lymph node metastasis and hemoglobin &lt;10 g/dl before CRT were poor prognostic factors for both PFS and OS in the whole group. When stage III cases were evaluated separately, the cumulative cisplatin dose below 200 mg was also found to be a significant poor prognostic factor in OS (HR 1.79, 95% CI, 1.1 to 3.0, p=0.031). Conclusions: The study revealed that a cumulative cisplatin dose exceeding 200 mg, particularly in patients with lymph node metastasis, significantly improved OS. Factors such as anemia, toxicity-related challenges, and comorbidities were identified as critical considerations in treatment planning. These findings emphasize the delicate balance between maximizing therapeutic efficacy and managing toxicity, guiding personalized treatment approaches for locally advanced cervical cancer. [Table: see text]

Clinical outcomes of transarterial chemoembolization in Child-Turcotte Pugh class A patients with a single small (≤3cm) hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is one of the standard modalities used to treat unresectable hepatocellular carcinoma (HCC), but the effectiveness of TACE for treating patients with a solitary small (≤3cm) HCC and well-preserved liver function has not been definitively established. This study aimed to determine the therapeutic impact of TACE in patients with these characteristics. This multicenter (four university hospitals) retrospective cohort study analyzed the medical records of 250 patients with a solitary small (≤3cm) HCC and Child-Turcotte-Pugh (CTP) class A liver function diagnosed over 10years. Posttreatment outcomes, including overall survival (OS), recurrence-free survival (RFS), and adverse events, were assessed following TACE therapy. One hundred and thirty-eight of the 250 patients (55.2%) treated with TACE achieved complete remission (CR). Overall median OS was 77.7months, and median OS was significantly longer in the CR group than in the non-CR group (89.1 vs. 58.8months, P=0.001). Median RFS was 19.1months in the CR group. Subgroup analysis identified hypertension, an elevated serum albumin level, and achieving CR as significant positive predictors of OS, whereas diabetes, hepatitis c virus infection, and tumor size (>2cm) were poor prognostic factors of OS. The study demonstrates the effectiveness of TACE as a viable alternative for treating solitary small (≤3cm) HCC in CTP class A patients.

Overexpression of cyclin F/CCNF as an independent prognostic factor for poor survival in clear cell renal cell carcinoma

Cyclin F (encoded by CCNF gene) has been reported to be implicated in the pathobiology of several human cancers. However, its potential clinical significance in clear cell renal cell carcinoma (ccRCC) remains unknown. The present study aimed to evaluate the potential significance of cyclin F, assessed by immunohistochemical (IHC) staining and molecular (bioinformatics) techniques, as a prognostic marker in ccRCC in relation to clinicopathological features and outcomes. IHC staining was performed using two independent ccRCC tissue array cohorts, herein called tissue macroarray (TMA)_1 and tissue microarray (TMA)_2, composed of 108 ccRCCs and 37 histologically normal tissues adjacent to the tumor (NAT) and 192 ccRCCs and 16 normal kidney samples, respectively. The mRNA expression data were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) public datasets, followed by bioinformatics analysis of biological mechanisms underlying prognosis. The relationship between immune cell infiltration level and CCNF expression in ccRCC was investigated using the Tumor Immune Estimation Resource 2.0 (TIMER2) and Gene Expression Profiling Interactive Analysis 2 (GEPIA2). Cyclin F expression was significantly elevated in ccRCC lesions compared to both NAT and normal renal tissues. Likewise, CCNF mRNA was markedly increased in ccRCCs relative to non-cancerous tissues. In all analyzed cohorts, tumors with features of more aggressive behavior were more likely to display cyclin F/CCNF-high expression than low. Furthermore, patients with high cyclin F/CCNF expression had shorter overall survival (OS) times than those with low expression. In addition, multivariable analysis revealed that cyclin F/CCNF-high expression was an independent prognostic factor for poor OS in ccRCC. Enrichment analysis for mechanistically relevant processes showed that CCNF and its highly correlated genes initiate the signaling pathways that eventually result in uncontrolled cell proliferation. CCNF expression was also correlated with immune cell infiltration and caused poor outcomes depending on the abundance of tumor-infiltrating immune cells in ccRCC. Our findings suggest that cyclin F/CCNF expression is likely to have an essential role in ccRCC pathobiology through regulating multiple oncogenic signaling pathways and affecting the tumor immune microenvironment and may serve as prognostic biomarker and promising therapeutic target in ccRCC.