Significant Differences In Survival Outcomes Research Articles

A Case Series and Systematic Review: Results of Surgical Management of Glaucoma Drainage Device Tube Exposure

Objective: To present a case series of patients who underwent surgical repair for glaucoma drainage device (GDD) tube exposure and conduct a systematic review to analyze results of various surgical techniques. Materials and Methods: This study provides the details of GDD tube exposure repair at our hospital. Additionally, a systematic review was conducted using electronic databases including EMBASE, MEDLINE, and CENTRAL. Data extraction and analysis included demographic information, surgical techniques, results, and duration of follow-up. Results: We reported nine cases of GDD tube exposure repair, with additional 109 cases from 24 previous studies. One of our challenging cases encountered multiple tube revision failures by the patch graft technique; the exposure issue was sustainably resolved by a hinge scleral flap with buccal mucosal graft technique. Of the 118 cases, various surgical techniques were used, including patch grafts, hinge scleral flaps, primary conjunctival closure and rerouting. Among the cases, 61.6% were classified as difficult cases. The overall first, fifth and thirteenth-year survival ratewas 90.7%, 86.2% and 86.2%, respectively. Rerouting and scleral flap/tunnel techniques demonstrated the highest survival rate. No statistically significant differences in survival outcomes were observed among patch graft, scleral flap/tunnel and rerouting method (P = 0.129). The mean survival duration was 33.54 months. The duration of follow-up was 35.01 months. Conclusion: Surgical management of GDD tube exposure yields favorable outcomes. A hinge scleral flap with buccal mucosal grafts can be a good option to treat challenging cases. The findings can shape an algorithm to manage GDD tube exposure.

The impact of positive resection margin in perihilar cholangiocarcinoma, ductal margin vs radial margin.

Resection margin status is the important prognostic factor in resected perihilar cholangiocarcinoma (pCCA). Although the impact of ductal margin (DM) was reported in many studies, the influence of radial margin (RM) is unclear. This study aims to investigate the effect of positive RM on survival. Patients with pCCA underwent curative resection between 2013 and 2018 were retrospectively reviewed. Resection margin status was divided into negative resection margin (R0) and positive resection margin (R1); positive RM alone (RM+) and positive DM with or without positive RM (DM+). Of the 167 pCCA patients, 62 (37.1%) had R1 margin. Among 62 R1 patients; 17 (27.4%) had positive DM alone, 20 (32.3%) had positive RM alone and 25 (40.3%) had both positive DM and RM. The R1 patients had a significantly greater number of lymph node metastasis (LNM) and advanced tumor staging than R0 patients, however there was no difference between the RM + and DM + patients. The median survival time of patients with RM + was significantly poorer than R0 patients (13.8 vs. 24.5 months; p < 0.001, respectively) and similar to the DM + patients (9.1 months, p = 0.556). However, in patients with LNM, those who underwent R0 resection had no statistically significant difference in survival outcomes compared to those with R1 resection. Positive resection margin remains the important prognostic factor, and positive RM is common in these patients. Positive RM also had a comparable effect on survival as positive DM. As a result, in pCCA, surgical resection should target both RM and DM.

Comparative analysis of manual vs. mechanical suturing techniques in esophagectomy: A propensity score‑matched study of long‑term outcomes.

Esophageal cancer, particularly esophageal squamous cell carcinoma (ESCC), is a major health concern worldwide, particularly in China. Surgical resection is still considered the primary curative treatment for this disease. However, the effect of different surgical methods-traditional hand-sewn anastomosis and modern mechanical anastomosis-remains controversial. A retrospective study was thus performed to elucidate how these two techniques affected the clinical prognosis of patients. Data were retrospectively collected from the comprehensive Esophageal Cancer Case Management Database of Sichuan Cancer Hospital and Institute (Chengdu, China), covering the period from 2010 to 2017. The cohort consisted of patients who underwent esophagectomy for ESCC, divided into two groups based on the suturing technique used: Manual suturing (MS) and mechanical suturing (MeS). A total of four causal inference methods for retrospective studies, namely inverse probability of treatment weighting, standardized mortality ratio weighting, overlap weighting and propensity score matching analysis, were used to minimize potential selection bias. The primary outcome evaluated was overall survival (OS), allowing for a direct comparison of the long-term efficacy of the two suturing methods. In a retrospective analysis of 2,510 patients undergoing esophagectomy, significant differences in OS were observed between the MeS group and the MS group (hazard ratio: 0.84; 95% confidence interval: 0.75-0.95; P=0.004). However, after matching or weighting based on causal inference analyses, no significant differences in survival outcomes between groups were obtained. The equivalence in outcomes suggests that either suturing method may be equally viable in clinical practice, offering flexibility in surgical decision-making without compromising OS.

Comparison of immune checkpoint inhibitor plus chemotherapy or ipilimumab plus nivolumab-based therapy for NSCLC patients with PD-L1 TPS (1–49 %): TOPGAN2023-01

IntroductionImmune checkpoint inhibitors (ICIs) plus chemotherapy is now a standard treatment for non-small cell lung cancer (NSCLC). Whether ICI plus chemotherapy (ICI-chemo) or ipilimumab plus nivolumab (I-N)-based therapy is superior for patients with NSCLC with a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) of 1–49 % has not been evaluated. MethodsThis multicenter retrospective study included NSCLC patients with a TPS score of 1–49 %, who began first-line chemotherapy. Propensity score matching analysis was used to adjust for various confounders and evaluate treatment efficacy. ResultsA total of 401 patients were enrolled, of whom 308 received ICI-chemo and 93 received I-N-based therapy. The median OS was 21.0 months in the ICI-chemo group and 20.0 months in the I-N-based therapy group. After propensity score matching, there was no difference in OS or PFS between the ICI-chemo group and the I-N-based therapy group (OS: hazard ratios (HR), 0.83; 95 % confidence interval [CI], 0.54–1.26, PFS: HR, 0.72; 95 % CI, 0.52–1.00). Among PD-L1 TPS 25–49 %, there was a tendency for OS to be favorable for the ICI-chemo group (OS: HR, 0.30; 95 % CI, 0.09–0.85). Treatment discontinuation occurred for 26.2 % of the patients in the ICI-chemo group and 41.9 % in the I-N-based therapy group. ConclusionsAmong PD-L1 TPS 1–49 %, there was no significant difference in survival outcomes between the ICI-chemo group and the I-N-based therapy group. Based on the results of a subgroup analysis, ICI-chemo may be superior for treating NSCLC with a TPS of 25–49 %.

What’s the optimal temperature control strategy in patients receiving ECPR after cardiac arrest? A network meta-analysis

BackgroundThe optimal temperature control strategy in extracorporeal cardiopulmonary resuscitation (ECPR) patients is unknown, and several trials have reported conflicting results regarding its effectiveness. We aimed to conduct a systemic review and network meta-analysis (NMA) to assess the efficacy of temperature control in ECPR patients. MethodsDatabase searching of studies reporting data on temperature control strategy during ECPR in MEDLINE, EMBASE, Scopus, and Cochrane Library was performed. Primary outcomes were overall survival and neurological outcome. Pairwise meta-analysis and Bayesian NMA were performed on studies comparing outcomes among groups of moderate hypothermia (32–34 °C), mild hypothermia (34.1–36 °C) and normothermia (36.1–37.5 °C). ResultsNineteen retrospective studies were included (5622 patients). Statistically significant differences in good neurological outcome were observed in the direct comparison of moderate hypothermia and mild hypothermia (OR, 1.73; 95 % CI: 1.07–2.81) as well as moderate hypothermia and normothermia (OR, 2.14; 95 % CI: 1.24–3.67), but no significant differences were found in the NMA result. There was no difference in either survival outcome or the incidence of bleeding complications among any groups according to direct or indirect analysis. ConclusionsDirect evidence suggests that moderate hypothermia might be associated with improved neurological outcomes in ECPR patients. However, no significant differences in survival outcomes were observed in either the direct or NMA results. Given the lower level of the evidence, interpretation should be made with caution.

The role of NOP58 in prostate cancer progression through SUMOylation regulation and drug response.

Prostate cancer is one of the leading causes of cancer-related deaths in men. Its molecular pathogenesis is closely linked to various genetic and epigenetic alterations, including posttranslational modifications like SUMOylation. Identifying biomarkers that predict outcomes and specific therapeutic targets depends on a comprehensive understanding of these processes. With growing interest in SUMOylation as a mechanism affecting prostate cancer-related genes, this study aimed to investigate the central role of SUMOylation in prostate cancer prognostics, focusing on the significance of NOP58. We conducted a comprehensive bioinformatics analysis, integrating differential expression analysis, survival analysis, gene set enrichment analysis (GSEA), and single-cell transcriptomic analyses using data from The Cancer Genome Atlas (TCGA). Key genes were identified through intersections of Venn diagrams, Boralta algorithm signatures, and machine learning models. These signaling mechanisms were validated through experimental studies, including immunohistochemical staining and gene ontology analyses. The dual-gene molecular subtype analysis with SUMO1, SUMO2, and XPO1 genes revealed significant differences in survival outcomes across molecular subtypes, further emphasizing the potential impact of NOP58 on SUMOylation, a key post-translational modification, in prostate cancer. NOP58 overexpression was strongly associated with shorter overall survival (OS), progression-free interval (PFI), and disease-specific death in prostate cancer patients. Immunohistochemical analysis confirmed that NOP58 was significantly overexpressed in prostate cancer tissues compared to normal tissues. ROC curve analysis demonstrated that NOP58 could distinguish prostate cancer from control samples with high diagnostic accuracy. Gene Ontology analysis, along with GSVA and GSEA, suggested that NOP58 may be involved in cell cycle regulation and DNA repair pathways. Moreover, NOP58 knockdown led to increased BCL2 expression and decreased Ki67 levels, promoting apoptosis and inhibiting cell proliferation. Colony formation assays further showed that NOP58 knockdown inhibited, while its overexpression promoted, colony formation, highlighting the critical role of NOP58 in prostate cancer cell growth and survival. Additionally, NOP58 was linked to drug responses, including Methotrexate, Rapamycin, Sorafenib, and Vorinostat. NOP58 is a key regulator of prostate cancer progression through its mediation of the SUMOylation pathway. Its expression level serves as a reliable prognostic biomarker and an actionable therapeutic target, advancing precision medicine for prostate cancer. Targeting NOP58 may enhance therapeutic efficacy and improve outcomes in oncology.

Bladder transitional cell carcinoma anatomic primary site as a predictor of survival and mortality: a population-based retrospective cohort study

Background: Bladder cancer is a heterogeneous disease with varying prognostic outcomes based on the primary tumor site within the bladder. This study aims to evaluate the impact of tumor location on overall survival and cancer-specific survival in bladder cancer patients. Methods: The authors conducted a retrospective cohort study using data from the Surveillance, Epidemiology, and End Results database. Patients with primary transitional cell carcinoma of the bladder were categorized based on their tumor locations. Survival outcomes were assessed using Kaplan–Meier analysis and Cox proportional hazards regression models, adjusted for age, sex, race, cancer stage, and treatment modalities. Additionally, binary logistic regression models were employed to predict overall mortality (OM) and cancer-specific mortality (CSM) at 1, 5, and 10 years. Results: The study included 107 909 patients diagnosed with primary bladder cancer between 2000 and 2021. Significant differences in survival outcomes were observed across different tumor sites. Bladder cancer originating in the urachus had the worst OS before 100 months and the worst CSS overall. Tumors in the anterior wall showed the worst OS after 100 months. In the Cox multivariable analysis, anterior wall tumors were associated with a 1.513-fold increased risk of death compared to lateral wall tumors. The binary logistic regression models showed that anterior wall tumors predicted the highest OM and CSM at 1-year, while urachal tumors had the worst outcomes at 5 and 10 years. Conclusions: The primary site of bladder cancer is a significant predictor of survival outcomes, with tumors in the urachus and anterior wall associated with a poorer prognosis. These findings underscore the importance of considering tumor location in the prognosis and management of bladder cancer. Future studies should aim to validate these findings in more diverse populations and explore the underlying biological mechanisms that drive these differences.

Machine learning-based individualized survival prediction model for prognosis in osteosarcoma: Data from the SEER database.

Patient outcomes of osteosarcoma vary because of tumor heterogeneity and treatment strategies. This study aimed to compare the performance of multiple machine learning (ML) models with the traditional Cox proportional hazards (CoxPH) model in predicting prognosis and explored the potential of ML models in clinical decision-making. From 2000 to 2018, 1243 patients with osteosarcoma were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Three ML methods were chosen for model development (DeepSurv, neural multi-task logistic regression [NMTLR]) and random survival forest [RSF]) and compared them with the traditional CoxPH model and TNM staging systems. 871 samples were used for model training, and the rest were used for model validation. The models' overall performance and predictive accuracy for 3- and 5-year survival were assessed by several metrics, including the concordance index (C-index), the Integrated Brier Score (IBS), receiver operating characteristic curves (ROC), area under the ROC curves (AUC), calibration curves, and decision curve analysis. The efficacy of personalized recommendations by ML models was evaluated by the survival curves. The performance was highest in the DeepSurv model (C-index, 0.77; IBS, 0.14; 3-year AUC, 0.80; 5-year AUC, 0.78) compared with other methods (C-index, 0.73-0.74; IBS, 0.16-0.17; 3-year AUC, 0.73-0.78; 5-year AUC, 0.72-0.78). There are also significant differences in survival outcomes between patients who align with the treatment option recommended by the DeepSurv model and those who do not (hazard ratio, 1.88; P < .05). The DeepSurv model is available in an approachable web app format at https://survivalofosteosarcoma.streamlit.app/. We developed ML models capable of accurately predicting the survival of osteosarcoma, which can provide useful information for decision-making regarding the appropriate treatment.

A metagene based similarity network fusion approach for multi-omics data integration identified novel subtypes in renal cell carcinoma.

Renal cell carcinoma (RCC) ranks among the most prevalent cancers worldwide, with both incidence and mortality rates increasing annually. The heterogeneity among RCC patients presents considerable challenges for developing universally effective treatment strategies, emphasizing the necessity of in-depth research into RCC's molecular mechanisms, understanding the variations among RCC patients and further identifying distinct molecular subtypes for precise treatment. We proposed a metagene-based similarity network fusion (Meta-SNF) method for RCC subtype identification with multi-omics data, using a non-negative matrix factorization technique to capture alternative structures inherent in the dataset as metagenes. These latent metagenes were then integrated to construct a fused network under the Similarity Network Fusion (SNF) framework for more precise subtyping. We conducted simulation studies and analyzed real-world data from two RCC datasets, namely kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP) to demonstrate the utility of Meta-SNF. The simulation studies indicated that Meta-SNF achieved higher accuracy in subtype identification compared with the original SNF and other state-of-the-art methods. In analyses of real data, Meta-SNF produced more distinct and well-separated clusters, classifying both KIRC and KIRP into four subtypes with significant differences in survival outcomes. Subsequently, we performed comprehensive bioinformatics analyses focused on subtypes with poor prognoses in KIRC and KIRP and identified several potential biomarkers. Meta-SNF offers a novel strategy for subtype identification using multi-omics data, and its application to RCC datasets has yielded diverse biological insights which are highly valuable for informing clinical decision-making processes in the treatment of RCC.

Prognostic Impact of Tumor Growth Rate During Second-line Chemotherapy in Patients With Gastric Cancer.

Despite the remarkable developments in chemotherapy for gastric cancer (GC), rapid tumor growth is sometimes experienced during chemotherapy. This study investigated the association of tumor growth rate (TGR) during second-line chemotherapy with the prognosis of patients with GC. We retrospectively reviewed 29 patients with GC treated with nab-paclitaxel plus ramucirumab as second-line chemotherapy between 2017 and 2019 at Osaka Metropolitan University. Of them, 13 cases with target lesions were classified into two groups according to TGR using a cutoff value of 0.25. Clinicopathological factors and survival outcomes were compared between the high TGR (n=5) and low TGR (n=8) groups. The median duration of first-line chemotherapy was significantly longer in the high TGR group than in the low TGR group [median 298 days vs. 72.5 days, p=0.030]. Progressive disease (PD) was observed in 60% of patients with high TGR, whereas stable disease (SD) was observed in 75% patients with low TGR. The median survival time (MST) after starting chemotherapy was 488 days in the low TGR group but was not reached in the high TGR group (log rank p=0.215). The MST after PD was 145 days in the low TGR group but was not estimated in the high TGR group (log rank p=0.345). Based on the absence of significant differences in survival outcomes between the high and low TGR groups, sequential late-line chemotherapy might be considered important, even for patients with high TGR.

Medial opening wedge high tibial osteotomy performs similarly irrespective of body mass index.

This study investigates the effect of the body mass index (BMI) on the early (2 years) to midterm (5 years) results of medial opening wedge high tibial osteotomy (MOWHTO). A prospectively maintained single-centre database of 1138 knee osteotomies, between 2002 and2022, was retrospectively reviewed. Adult patients who underwent MOWHTO for symptomatic unicompartmental medial knee osteoarthritis (OA), with varus knee malalignment, having failed conservative management, were included. Patients were categorized into threegroups according to their BMI as per the classification from the National Institute for Health and Care Excellence (NICE): the healthy weight (HW) group (BMI of 18.5-24.9 kg/m2), the overweight (OW) (BMI of 25-29.9 kg/m2), and the obesity (OB) group (BMI ≥ 30 kg/m2). Multiple patient-reported outcome measures (n = 6) were recorded preoperatively and at 2 and 5 years postoperatively. Deformity analysis was undertaken preoperatively and postoperatively. The relative risk (RR) of the complications between the HW, OWand OB groups was calculated. The rate of conversion to arthroplasty, and 5and 10 years survivorship were recorded, as well as the hazard ratio (HR) of BMI on survivorship. A total of 574 cases were included in the study: the HW group (n = 96), the OW group (n = 233)and the OB group (n = 245), with a mean BMI of 23 ± 1.5 kg/m2, 27.4 ± 1.4 kg/m2 and 34.4 ± 3.8 kg/m2, respectively. The mean follow-up was 13.3 years (4.8-20.3). The mean mechanical tibiofemoral angle corrections were in the HW group: 7.1 ± 3°, OW group: 6.6 ± 3.5°and OB group: 7.1 ± 3.8°, with no intergroup significant difference (p = n.s.). Clinically, despite lower preoperative scores in the OW and OB groups, no difference was observed postoperatively amongst the three groups. The overall complication rate was 12.5% in the HW group, 6.8% in the OW group, and 9.8% in the OB group. There was no significant difference in the RR of complications between the HW and OW groups (RR = 0.6, 95% confidence interval [CI] = 0.3-1.3)(p = 0.2), and the HW and OB groups (RR = 0.8; 95% CI = 0.3-2.2)(p = 0.7). There was no overall significant difference in survival outcomes based on the BMI between the threegroups (p = 0.4). The HR of conversion to arthroplasty between the HW and OW groups was 1.4 [95% CI = 0.6-3.5](p = 0.5)and between the HW and OB groups was 1.8 [95% CI = 0.8-4.4] (p = 0.2). BMI has no significant effect on either the radiological corrections, clinical outcomes, complicationsor survivorship of MOWHTO at short- to medium-term follow-up. No specific cutoff point for BMI can be recommended as a contraindication to MOWHTO. Level IV, Retrospective cohort study.

High-grade B-cell lymphoma, not otherwise specified: CNS involvement and outcomes in a multi-institutional series

AbstractLittle is known about the central nervous system (CNS) risk in high-grade B-cell lymphoma, not otherwise specified (HGBL NOS). Hence, we sought to describe the rates of baseline CNS involvement, risk of CNS recurrence after primary therapy, and management strategies in HGBL NOS. In this multicenter retrospective study, we included 160 adults with newly diagnosed HGBL NOS treated between 2016 and 2021 at 20 US institutions. Eleven patients (7%) had baseline CNS involvement at diagnosis (leptomeningeal = 6, parenchymal = 4, and both = 1). Baseline CNS involvement was significantly associated only with MYC rearrangement (OR = 3.5) and testicular (in men) or female pelvic (in women) involvement (OR = 8.1). There was no significant difference in survival outcomes between patients with HGBL NOS with (median PFS = 4 years) or without (median PFS = 2.4 years) baseline CNS involvement (P = 0.45). The cumulative incidence of CNS recurrence at 3 years was 11%. Patients with baseline CNS involvement were at the highest risk (48.5% vs 8% for those without baseline CNS involvement) and were excluded from the risk factors analysis for CNS recurrence. The risk for CNS recurrence was significantly associated with blood or bone marrow involvement, CD5 expression, non–germinal center B-cell subtype, and “dual-expresser lymphoma” phenotype, however, high CNS IPI was not. The prognosis of relapsed HGBL NOS was poor, regardless of whether recurrence was systemic or limited to the CNS, and with currently available salvage strategies, including autologous transplantation and chimeric antigen receptor T-cell modalities, almost all patients with CNS recurrence ultimately succumbed to their disease.

Pan-immune-inflammation value: a new prognostic index in epithelial ovarian cancer

BackgroundEpithelial ovarian cancer (EOC) is one of the deadliest gynaecological malignancies worldwide. The aim of this retrospective study was to create a predictive scoring model based on simple immunological and inflammatory parameters to predict overall survival (OS) and progression-free survival (PFS) in patients with EOC.MethodsWe obtained 576 EOC patients and randomly assigned them to the training set (n = 405) and the validation set (n = 171) in a ratio of 7:3. We retrospectively evaluated the association between PIV and OS and PFS using a novel immunoinflammatory marker, according to the optihmal treshold of PIV, we divided the patients into two different subgroups, high PIV (PIV > 254.9) and low PIV (PIV ≤ 254.9). Pan-immune Inflammatory Value (PIV) was computed as follows: neutrophil count (109/L) × platelet count (109/L) × monocyte count (109/L)/lymphocyte count (109/L). Then developed a simple score prediction model based on several independent prognostic parameters using Cox regression analysis. We used receiver operator characteristic (ROC) curves, calibration plots, and decision analysis (DCA) curves to evaluate the performance of the model. Finally, we used Kaplan-Meier curves to ensure that the model could distinguish well between low- and high-risk groups.ResultsThere was a significant difference in survival outcomes between high PIV (PIV > 310.2) and low PIV (PIV ≤ PIV310.2) (3-year survival rates of 61.34% and 76.71%, respectively); 5-year OS, 25.21% and 51.14%, respectively; 3-year PFS, 40.90% and 65.30%; 5-year PFS, 19.33% and 39.73%, respectively). Column plots of OS and PFS were constructed using independent prognostic factors. In the training module, the 3-, 5-, and 10-year AUCs for OS and PFS column charts were 0.713, 0.796, 0.839, and 0.730, 0.799, 0.826, respectively.In the validation cohort, the 3-, 5-, and 10-year AUCs for OS and PFS column charts were 0.676, 0.803, 0.685, and 0.700, respectively, 0.754, 0.727. The calibration curves showed good agreement between predicted survival and actual observations. The decision analysis curves also showed that the current model has good accuracy and clinical applicability. 3-year OS was 61.34% and 76.71%, respectively; 5-year OS was 25.21% and 51.14%, respectively; 3-year PFS was 40.90% and 65.30%, respectively; 5-year PFS was 19.33% and 39.73%, respectively.ConclusionsWe constructed and validated a PIV-based nomogram to predict OS and PFS in EOC patients, with a view to helping gynaecologists converge on oncologists in their treatment and follow-up expertise in epithelial ovarian cancer.

Progression patterns, resistant mechanisms and subsequent therapy for ALK-positive NSCLC in the era of second-generation ALK-TKIs

BackgroundIn the era of second-generation ALK tyrosine kinase inhibitors (ALK-TKIs), there was a paucity of data regarding the progression patterns, resistant mechanisms, and subsequent therapeutic approaches for ALK-positive (ALK+) non-small cell lung cancer (NSCLC).MethodsPatients with advanced ALK+ NSCLC were retrospectively selected from our center. Cohort 1 consisted of patients who experienced disease progression after receiving first-line alectinib treatment (n = 20), while Cohort 2 included patients who progressed following sequential treatment with crizotinib and second-generation ALK-TKIs (n = 53). Oligo-progression was defined as the occurrence of disease progression in no more than three lesions. Symptomatic progression was determined when patients developed new symptoms or experienced worsening of pre-existing symptoms during radiological progression.ResultsThe incidence of central nervous system (CNS) progression and symptomatic CNS progression was significantly lower in Cohort 1 compared to patients treated with crizotinib, with rates of 15.0% vs. 56.6% (p = 0.002) and 5.0% vs. 32.1% (p = 0.016), respectively. A total of 60.3% (44/73) patients underwent repeated biopsy and next-generation sequencing subsequent to the second-generation ALK-TKI resistance, with secondary mutation in ALK kinase domain emerging as the predominant mechanism of resistance (56.8%). Local therapy was applied to 50% of oligo-progression cases. Subsequent ALK-TKIs demonstrated significantly prolonged progression-free survival (PFS) (8.6 m vs. 2.7 m, p = 0.021, HR = 0.43, 95%CI: 0.15–0.85) and long-term overall survival (OS) (NA vs. 11.9 m, p = 0.132, HR = 0.50, 95%CI: 0.18–1.25) in patients harboring ALK resistance mutations, compared to those without such mutations. For patients without ALK-resistant mutations following progression on second-generation ALK-TKIs, there was no statistically significant difference in survival outcomes between subsequent chemotherapy or alternative ALK-TKI treatments.ConclusionsFirst-line alectinib demonstrated superior efficacy in protecting the CNS compared to crizotinib. For patients with ALK-resistant mutations following the resistance to second-generation ALK-TKIs, appropriate sensitive ALK-TKI should be administered; for those without such mutations, the selection of chemotherapy or third-generation ALK-TKI should be based on the patient’s overall physical health and personal preferences.

A comparative study of double track anastomosis and tubular esophagogastric anastomosis in laparoscopic radical proximal gastrectomy for upper gastric carcinoma.

e16117 Background: For the upper gastric cancer, especially adenocarcinoma at the esophagogastric junction, the optimal surgical method is still controversial. The purpose of the study is to evaluate the safety and clinical effect of double track (DT) anastomosis in laparoscopic radical proximal gastrectomy (LRPG). Methods: A retrospective analysis was conducted involving 243 patients who underwent LRPG in the Department of Gastrointestinal Surgery, Qilu Hospital of Shandong University from Jan. 2017 to Dec. 2020. Patients were divided into tubular esophagogastric (TG) anastomosis group and double track (DT) anastomosis group, according to the digestive tract reconstruction. Their intraoperative conditions, perioperative recovery and postoperative follow-up were compared. Patients were divided into ≥60 and &lt; 60 groups according to age, to analysis the pros and cons of the two surgical methods in different age groups. According to whether or not indocyanine green (ICG) tracer technology was used during the operation, DT group was also divided into ICG group and non-ICG group. Results: Compared with the TG group, the DT group had less volume of gastric tube drainage, shorter gastric tube drainage time and proton pump inhibitors application time, and lower reuse rate of proton pump inhibitors. However, the DT group had more total operation time and lymph node dissection time. The median follow-up time of the patients was 36.0 months. At the end of study, the 1-year OS rate and DFS rate were 94.2% and 92.6% in the TG group and 95.8% and 93.7% in the DT group. The 3-year OS rate and DFS rate were 90.2% and 85.2% in the TG group and 91.9% and 87.7% in the DT group. And there was no significant difference in survival outcomes between the two groups. The DT group had a lower anastomotic stenosis at 3rd month after surgery. Moreover, the incidence of reflux esophagitis and Gerd Q score in the DT group were lower compared with the TG group at 3rd month, 1st year and 3rd year after surgery. In addition, elderly patients had a higher incidence of short-term complications in DT group compared with TG group. In the ICG analysis, the ICG DT group had significantly shorter total operation time and lymph node dissection time, less intraoperative blood loss and more lymph nodes obtained compared with the non-ICG DT group. Conclusions: DT anastomosis is a safe and effective way in LRPG for upper gastric carcinoma. Although the operation time of it is longer than that of TG anastomosis, it has a better anti-reflux effect and reduces the incidence of dysphagia and anastomotic stenosis. In elderly patients, it is important to minimize operative time and better to use TG anastomosis. The application of ICG tracer technique in LRPG has positive significance.

Machine learning identification of hypoxia-related genes and prognostic risk-scoring model for effective survival stratification in hepatocellular carcinoma.

e16261 Background: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality globally, where treatment and prognostic assessment have important implications in clinical practice. Hypoxia, as a common feature within solid tumors, can directly change the tumor microenvironment, which affects the efficacy of cancer treatment and prognosis. In this study, we constructed and validated a hypoxia-based prognostic model using bioinformatics and machine learning. Methods: Two public datasets, GSE14520 and GSE41666, were collected from the Gene Expression Omnibus: (1) HCC tumor tissues compared to adjacent normal tissues (N = 214) and (2) HepG2 cells under normoxic and hypoxic conditions (N = 6). Differential expression analysis was performed to identify HCC characteristic genes and hypoxia-related genes, including their common genes (HCC-Hypoxia Overlap genes, HHOs). Using RNA-seq data of HCC patients (N = 367) from the TCGA Liver Cancer (LIHC) database, univariate Cox regression models were identified, and the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm selected hypoxia-characteristic genes for the multivariate survival model. A hypoxia-related risk score was calculated based on the model of these characteristic genes and dichotomized cases into high-risk (HR) and low-risk (LR) groups. The model was validated using liver cancer cases (N = 232) from the International Cancer Genome Consortium database (ICGC-LIRI-JP). Results: Through differential expression analysis of the two datasets, we identified 52 HHOs. Univariate Cox analysis of these HHOs indicated that 21 genes were significantly associated with HCC patient survival. Through LASSO regression analysis, a total of 9 characteristic genes, including CENPA, KIF20A, DLGAP5, HMMR, UPB1, AFM, CABYR, PHLDA2, and N4BP2L1 were ultimately retained in the survival model. Based on these 9 genes, TCGA-LIHC samples were classified into HR and LR groups, and Kaplan-Meier (KM) analysis revealed significant differences in survival outcomes (p &lt; 0.032). Risk scoring of the ICGC-LIRI-JP validation set classified samples into HR and LR. KM analysis showed that the survival times of patients in the HR group were significantly shorter than those in the LR group (p &lt; 0.0001). Receiver Operating Characteristic Analysis analysis of the survival model showed area under the curve values of 0.815, 0.774, and 0.771 at 1, 2, and 3 years, respectively, demonstrating high performance in risk stratification. Conclusions: This study established a prognostic risk-scoring model based on 9 characteristic genes associated with hypoxia. This model can effectively stratify risks among HCC patients and demonstrate excellent performance in predicting survival. These findings may offer new biomarkers and therapeutic targets for the personalized treatment of HCC.

Effects of Adjuvant Chemotherapy on Oncologic Outcomes in Patients With Stage ⅡA Rectal Cancer Above the Peritoneal Reflection Who Did Not Undergo Preoperative Chemoradiotherapy

PurposeThis study aimed to evaluate the effects of adjuvant chemotherapy (AC) on oncologic outcomes for patients with stage IIA upper rectal cancer and to investigate whether AC is associated with improved survival outcomes. MethodsThis retrospective study comprised 432 patients with rectal cancer above the peritoneal reflection who had undergone curative resection without preoperative chemoradiotherapy between 2008 and 2016. This study cohort was divided according to whether AC was received (AC group) or not (no-AC group). Risk factors included obstruction, perforation, poorly-differentiated tumor, lympho-vascular invasion, perineural invasion, resection margin involvement, and < 12 lymph nodes harvested. ResultsAmong the 432 patients, 279 (64.6%) had received AC. The AC group had significantly higher 5-year overall survival (OS) rates than those of the no-AC group (93.2% vs. 84.6%, P = .001). Among patients with ≥ 1 risk factors, the AC group (n = 123) had significantly higher rates of 5-year recurrence-free survival (RFS) (81.6% vs. 64.1%, P = .01) and 5-year OS (88.8% vs. 69.0%, P = .001) than those of the no-AC group (n = 59). No significant difference in survival outcomes was observed between the 2 groups in patients aged > 65 years. ConclusionAC was significantly associated with better 5-year RFS and 5-year OS rates in patients with stage IIA rectal cancer above peritoneal reflection who did not receive preoperative chemoradiotherapy, especially in those with ≥ 1 risk factors.

Evolution and prognostic significance of HER-2 changes from primary to residual disease in patients with HER-2–negative breast cancer receiving neoadjuvant chemotherapy.

583 Background: HER-2 changes during the neoadjuvant chemotherapy has not been thoroughly evaluated. The current study aimed to analyze the HER-2 status changes from primary to residual disease in HER-2 negative patients after neoadjuvant chemotherapy and evaluate its impact in survival outcomes. Methods: HER-2 negative breast cancer patients with residual disease after NACT who had paired pre- and post-therapeutic HER2 testing results were retrospectively analyzed. Data on clinical and pathological characteristics, treatment information, and survival outcomes were collected for all eligible patients. HER2 changes from the primary to residual disease were described and logistic regression were performed to identify factors associated with HER2 changes. The Kaplan–Meier method and multivariate Cox regression were used for survival analysis. Results: 571 HER-2 negative breast cancer patients with residual disease after NACT were enrolled, including HER2-zero (35.2%, n=201) and HER2-low (64.8%, n=370) patients before NAC. The overall rate of HER-2 changes rate was 32.4% (negative to positive 1.1%, low to zero 15.4%, zero to low 15.9%). Among the patients with HER-2-zero before NAC, patients with HER-2 changes (zero to low) were likely to be hormone receptor positive (68.1% vs 36.7%, P&lt;0.0001) and had a higher proportion of patients with Ki-67≤20 (Ki-67≤20 27.5% vs 15.6%, P=0.035). Among the patients with HER2-low before NAC, a higher proportion of hormone receptor negative were observed in HER2 changes patients (low to zero) (31.8% vs 18.4%, P=0.008) and the Ki-67 is relatively high in HER-2 changes patients (Ki-76 &gt; 20 73.9% vs 65.0% P=0.030). Multivariable logistic regression analyses showed patients with hormone receptor positive before NAC were related to underwent HER2-zero transferring to HER2-low (OR, 3.436, P&lt;0.0001). The median follow-up time was 50.0 months. In the HER-2 zero group, HER2 changes (zero to low) was significantly associated with better DFS comparing with constant HER2-zero (HR0.49, P=0.01) after adjustment, with 4-year DFS rate was 80.1%,55.7% (Log-rank P =0.033). Subgroup analysis showed that in the hormone receptor positive subgroup, patients with HER2 zero to low has a significant better DFS than patients with constant HER2-zero (Log-rank P=0.037). In the HER2-low group, no significant differences in survival outcomes between constant HER2-low and HER2 low to zero (HR1.07, P=0.778). Conclusions: HER2 status showed instability from primary tumor to residual disease after neoadjuvant treatment. HER2 changes (zero to low) was associated with better DFS in HER-2 zero patients.

Prognostic Impact of CDKN2A Mutations Associated With Smoking and Drinking History in Japanese Digestive Cancers.

Organs of the digestive system are frequent sites of cancer development, and digestive tract cancers are the leading causes of death worldwide, including in Japan. Most of these cancers are associated with smoking or drinking habits. This study focused on the clinical and genomic characteristics of patients with these cancers using the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, which comprises a large volume of data on Japanese patients who have undergone tumor profiling gene panel tests. The genomic and clinical data from patients with digestive tract cancers registered in C-CAT between 2019 and 2023 were retrospectively reviewed. The data were derived from 412 patients with esophageal squamous cell carcinoma, 558 with gastric adenocarcinoma, 3,368 with colorectal adenocarcinoma, 139 with hepatocellular carcinoma, 2,050 with cholangiocarcinoma, and 2,552 with pancreatic ductal adenocarcinoma. CDKN2A, CDKN2B, and MTAP mutations were associated with both smoking and drinking history, and patients with these mutations had a worse prognosis. Almost all gene alterations in CDKN2B and MTAP were deletions, often accompanied by CDKN2A deletion. CDKN2A mutation emerged as the most decisive prognostic factor among these mutations. Although CDKN2A mutations were frequently seen in esophageal squamous cell carcinoma, cholangiocarcinoma, and pancreatic ductal adenocarcinoma, statistically significant differences in survival outcomes were only identified in the latter two. CDKN2A mutations were associated with smoking and drinking in digestive cancers. This mutation was prevalent among patients with cholangiocarcinoma and pancreatic ductal adenocarcinoma, for whom they could serve as prognostic factors.

Establishment and validation of a predictive model for tracheotomy in critically ill patients and analysis of the impact of different tracheotomy timing on patient prognosis

BackgroundIn critically ill patients receiving invasive mechanical ventilation (IMV), it is unable to determine early which patients require tracheotomy and whether early tracheotomy is beneficial.MethodsClinical data of patients who were first admitted to the ICU and underwent invasive ventilation for more than 24 h in the Medical Information Marketplace in Intensive Care (MIMIC)-IV database were retrospectively collected. Patients were categorized into successful extubation and tracheotomy groups according to whether they were subsequently successfully extubated or underwent tracheotomy. The patients were randomly divided into model training set and validation set in a ratio of 7:3. Constructing predictive models and evaluating and validating the models. The tracheotomized patients were divided into the early tracheotomy group (< = 7 days) and the late tracheotomy group (> 7 days), and the prognosis of the two groups was analyzed.ResultsA total of 7 key variables were screened: Glasgow coma scale (GCS) score, pneumonia, traumatic intracerebral hemorrhage, hemorrhagic stroke, left and right pupil responses to light, and parenteral nutrition. The area under the receiver operator characteristic (ROC) curve of the prediction model constructed through these seven variables was 0.897 (95% CI: 0.876–0.919), and 0.896 (95% CI: 0.866–0.926) for the training and validation sets, respectively. Patients in the early tracheotomy group had a shorter length of hospital stay, IMV duration, and sedation duration compared to the late tracheotomy group (p < 0.05), but there was no statistically significant difference in survival outcomes between the two groups.ConclusionThe prediction model constructed and validated based on the MIMIC-IV database can accurately predict the outcome of tracheotomy in critically ill patients. Meanwhile, early tracheotomy in critically ill patients does not improve survival outcomes but has potential advantages in shortening the duration of hospitalization, IMV, and sedation.