Statistical Difference In Overall Survival Research Articles

Outcomes of intra-aortic balloon pump in patients with advanced heart failure and cardiogenic shock undergoing heart transplantation

Abstract Background Intra-aortic balloon pump (IABP) is generally used as a short-term device to maintain adequate organ perfusion in patients with cardiogenic shock (CS). However, whether IABP improves clinical outcomes as a bridge therapy for heart transplant (HTx) remains controversial. Purpose Evaluate the survival rate 30 days after heart transplant (HTx) in patients with advanced heart failure (HF) and CS using IABP pre transplant compared to non-IABP group. Methods We retrospectively analyzed consecutive patients with advanced HF and CS, admitted in the cardiac intensive care unit (ICU) of a tertiary university center, between 2009 and 2020, who underwent HTx. Study group included patients submitted to IABP implantation before HTx, and a non-IABP group submitted to HTx without left ventricular mechanical support. Propensity Score Matching was used to pair the groups according to relevant clinical covariates. The primary outcome of survival rate 30 days after HTx was estimated by the Kaplan-Meier method. Results 326 were enrolled, 199 in IABP group and 127 in non-IABP group. For non-IABP and IABP group, respectively, the most frequent etiology was Chagas disease (29,9% and 47,2%, p=0,006) followed by idiopathic cardiomyopathy and ischemic cardiomyopathy, the majority of patients were male (63% and 61,3%, p=0,760), the mean age was 46,9 ± 14,4 and 46,5 ± 12 years (p=0,791) and mean left ventricular ejection fraction was 25,9 ± 9,5% and 23,5 ± 5,9% (p=0,010). The Simplified Acute Physiology Score 3 (SAPS 3) at ICU admission was compared in both groups, which was 36,8% ± 17,8% in non-IABP group and 32,6% ± 18,6% in IABP group (p=0,042). At 30 days after HTx, there was no statistical difference in overall survival (p=0,459) between the groups (IABP: 18,1% mortality; non-IABP: 14,2% mortality). Survival rate after HTx was also similar in patients with Chagas disease compared to the other etiologies in both study groups (IABP group: p=0,221; non-IABP group: p=0,421). Conclusion In patients with advanced HF and CS submitted to HTx, the survival rate 30 days after HTx was equivalent in the IABP and non-IABP groups. In patients with Chagas disease the survival was also similar compared to other etiologies in both groups.Characteristics according to groupsKaplan-Meier survival estimates

Ultrasound-guided percutaneous microwave ablation for metabolic-associated fatty liver disease-related hepatocellular carcinoma (HCC) versus hepatitis virus B-related HCC: a propensity score matching study

Objectives To compare the long-term outcomes of microwave ablation (MWA) for primary hepatocellular carcinoma (HCC) in patients with metabolic-associated fatty liver disease (MAFLD) with those infected by hepatitis virus B (HBV). Methods The clinical data of HCC patients under the treatment of MWA were analyzed retrospectively between 2010 and 2021 at Chinese PLA General Hospital. Patients were divided into MAFLD-HCC and HBV-HCC group according to the chronic liver disease etiology. The propensity score matching (PSM) was performed to reduce the interference of confounders. The primary outcomes were overall survival (OS), recurrence-free survival (RFS), cancer-specific survival (CSS) and intrahepatic distant recurrence (IDR). Results A total of 648 patients (age range, 18–91 years) with 1019 lesions were enrolled including 601 with HBV-HCC and 47 with MAFLD-HCC. After a variable ratio of 1:n ≤ 4 PSM, 100 patients were included in the HBV-HCC and 41 in the MAFLD-HCC group. No statistical differences in OS and CSS (p = 0.880 and p = 0.980, respectively) were observed between the two groups in the matched cohort, while MAFLD-HCC exhibited better RFS and lower IDR rates compared to HBV-HCC (p = 0.043 and p = 0.041, respectively). Additionally, MAFLD-HCC generated lower ascending range in the liver function indexes like ΔALT (46.7 vs. 98.5, p < 0.001), ΔTBIL (1.9 vs. 7.5, p = 0.001) and ΔAST (38.1 vs. 148.6, p < 0.001) than HBV-HCC after MWA. Conclusions MWA is an effective treatment for HCC patients with MAFLD. The recurrence prognosis of MAFLD-HCC was better than HBV-HCC and the degree of liver injury after MWA was lower.

A simulated trial with reinforcement learning for the efficacy of Irinotecan and Ifosfamide versus Topotecan in relapsed, extensive stage small cell lung cancer

ObjectivesSynthetic data may proxy clinical data. At the absence of direct clinical data, this study aimed to compare Irinotecan and Ifosfamide (II) with Topotecan in synthetic, recurrent small cell lung cancer (SCLC) patients within a simulated clinical trial.Materials and methodsTwo simulation stages were conducted. Initially, 200 recurrent SCLC cases were simulated to replicate a previous phase 3 trial, testing the utility of Cox proportional hazards model and simulation methodology together, where patients were randomized to receive Cyclophosphamide, Adriamycin, Vincristine (CAV) or Topotecan. In the second stage, 600 recurrent SCLC patients were simulated and randomized to compare Topotecan versus II in terms of overall survival (OAS), using Reinforcement Learning (RL) and Cox proportional hazards model.ResultsCAV versus Topotecan comparison showed no statistical difference in overall survival (hazard ratio (HR): 0.89, 95% CI: 0.67–1.18, P = 0.418), aligning with the original clinical trial. For the Topotecan versus II comparison, the RL framework significantly favored the II arm (mean reward points: 193.43 versus − 251.82, permutation P < 0.0001). Likewise, II arm exhibited superior median OAS compared to Topotecan arm (11.12 versus 6.30 months). HR was 0.44 (95% CI: 0.38–0.52) with P < 0.0001, in favor of II.ConclusionArtificial trial results for CAV versus Topotecan matched the original trial, confirming indifference of OAS. Additionally, II yielded superior overall survival compared to Topotecan in recurrent SCLC patients. These demonstrate the potential of RL and simulation in conjunction with Cox modelling for similar studies. However, definitive conclusions necessitate a randomized clinical trial between II and Topotecan in this patient cohort.

Efficacy of First-Line Nivolumab Plus Ipilimumab in Unresectable Pleural Mesothelioma: A Multicenter Real-World Study (ImmunoMeso LATAM)

BackgroundThe phase 3 CheckMate-743 trial demonstrated a prolonged overall survival (OS) benefit with nivolumab plus ipilimumab over chemotherapy as first-line treatment in patients with unresectable pleural mesothelioma (PM). However, given that Latin American (LATAM) patients were notably underrepresented in this trial, we retrospectively assessed the effectiveness and safety of this regimen in this population. MethodsThis retrospective study included patients from 15 centers in LATAM with unresectable or metastatic PM treated with first-line nivolumab plus ipilimumab in a real-world data (RWD) scenario. Demographic, clinicopathological characteristics, and safety data were collected from medical charts. Progression-free survival (PFS), and OS were calculated using the Kaplan-Meier method. ResultsFrom June 2017, and January 2024 96 patients were included: epithelioid 78% (n = 75), 81% were ECOG 0-1 (n = 78). With a median follow-up of 24.1 months, median PFS and OS were 8 months (95% CI, 6.6-9.4), and 22 months (95% CI, 18.9-25), respectively. No statistical difference in OS was observed between epithelioid versus nonepithelioid histology (median 23 months vs. 19 months, respectively; P = .29). Treatment efficacy was also consistent among different clinical subgroups. Any and grade 3-4 adverse events were found in 43.1% (n = 28), and 18.5% (n = 12) of patients, respectively. Remarkably, no OS impact was observed in patients who had dose delay or treatment discontinuation due to immune-related adverse events, and those who experienced any adverse event. ConclusionsThis multicenter RWD study demonstrated the clinically meaningful benefit of first-line ipilimumab and nivolumab in LATAM patients with unresectable or metastatic PM, and data is consistent with previous trial findings.

346. ESOPHAGOGASTRIC JUNCTION SIEWERT II TUMORS, A CHALLENGE FOR THE SURGEON: RESULTS OF TRANSHIATAL EXTENDED GASTRECTOMY VS. IVOR LEWIS ESOPHAGECTOMY

Abstract Background Esophagogastric junction (EGJ) Siewert type II tumors pose unique challenges in terms of adequate surgical treatment due to their anatomical location and potential for abdominal and mediastinal lymph node metastasis. The optimal surgical approach for these tumors remains a topic of debate, with options including transhiatal extended gastrectomy or transthoracic esophagectomy. Understanding the different outcomes associated with these surgical interventions is crucial for informed decision-making and patient-tailored management. The aim of this study was to compare the perioperative and oncological outcomes of these two surgical technique to access which could be the treatment of choice for Siewert II type tumours. Methods This study is a retrospective non-randomized cohort study from a single center. We reviewed the data of all the patients who underwent surgery for EGJ Siewert type II tumors between December 2014 and February 2023. The patients were divided into two groups: those who underwent transthoracic esophagectomy were assigned to “TE group” (72 patients) and those who underwent transhiatal extended gastrectomy were assigned to “TEG group” (21 patients). Results Patients in the TEG group were older (p=0.011) and in worst clinical condition (Charlson Comorbidity Index 4.15±1.78 vs. 4.95±1.46, p=0.064). The tumour stage at the diagnosis was more advanced in the TE group (p=0.004), and upfront surgery was infrequent in this group (p&amp;lt;0.001). The average duration of surgery was higher in the TE group (p&amp;lt;0.001). No difference was seen in the tumour length (p=0.924), implying a statistically significant difference in the proximal margin length (p&amp;lt;0.001), and distal margin length (p&amp;lt;0.001), with a R0 resection rate higher in the TE group (93.1% vs. 66.7%, p=0.002). The higher rate of R1 resection in the TEG group was mainly due to proximal margin infiltration. No difference was seen in the number of harvested lymph nodes (p=0.339). Overall postoperative complications rates were similar (p=0.144). No differences were found in the length of ICU stay (p=0.676) and in hospital stay (p=0.075). At a median follow up of 20 months, there were no statistical differences in Overall Survival and Disease-Free Survival at 5 years. Conclusion Our data suggests that transthoracic esophagectomy for EGJ Siewert type II tumors should be the treatment of choice for patients in good clinical condition, but transhiatal extended gastrectomy could be a good choice for patients presenting in worse clinical condition. A multidisciplinary approach is essential for optimal patient care, and the selection of the surgical technique should be based on a thorough evaluation of the patient's condition and tumor characteristics

Impact of response to neoadjuvant chemotherapy on surgical modality in patients with T1-2N0-1M0 triple-negative breast cancer

PurposeMany T1-2N0-1M0 triple-negative breast cancer (TNBC) patients who undergo neoadjuvant chemotherapy (NAC) do not receive breast-conserving therapy (BCT) due to concerns about non-pCR or lymph node metastasis presence.MethodsT1-2N0-1M0 TNBC patients who underwent NAC between 2010 and 2017 were collected from the SEER database. Factors affecting surgical modalities were analyzed by multinomial logistic regression. The overall survival (OS) and breast cancer-specific survival (BCSS) were evaluated by Kaplan-Meier curves and Cox proportional hazards models. Further stratified subgroup analyses were performed based on the response to NAC and N-stage. Adjusted-hazard ratios were also calculated to exclude potential bias.ResultsA total of 1112 patients were enrolled (median follow-up: 81 months), 58.5% received BCT, 23.6% received reconstruction and 17.9% received mastectomy. Response to NAC and N-stage not only influenced the choice of surgical modality but also were independent predictors for OS and BCSS. The surgery-induced survival differences mainly affect OS. Survival analyses demonstrated that the 10-year OS of BCT was superior or equal to that of mastectomy even in patients with partial response (PR) (77.4% vs. 64.1%, P = 0.013), no response (NR) (44.9% vs. 64.2%, P = 0.33), or N1 stage (75.7% vs. 57.4%, P = 0.0021). In the N1-PR cohort, mastectomy may lead to worse OS (P = 0.0012). Besides, between reconstruction and BCT, there was no statistical difference in OS or BCSS (P > 0.05).ConclusionOur study reveals the necessity of breast surgical de-escalation. Besides, physicians should actively recommend reconstruction for individuals who strongly desire mastectomy.

Redox-state-regulating enzymes have prognostic value in diabetic endometrial cancer patients: impact of statin use?

The incidence of endometrial cancer is increasing, and oxidative stress has been suggested to play a vital role in its carcinogenesis. Statins have an impact on the cellular redox-state. The aim of this study was to determine the effects of statin use on redox-state regulating enzymes in endometrial cancer in women with type 2 diabetes. This retrospective study consisted of 119 women with type 2 diabetes who were diagnosed with endometrial cancer at Oulu University Hospital in Finland between 2007 and 2014. There were 58 statin users and 61 non-users based on medication use at the time of endometrial cancer diagnosis. The expression of redox-state regulating proteins nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) in the tumor samples was assessed immunohistochemically, and manganese superoxide dismutase (MnSOD) levels were measured both immunohistochemically and from serum samples. High MnSOD expression predicted better progression-free survival (PFS) in statin non-users in a univariate analysis (p=0.02). There was no statistical difference in overall survival (OS) or PFS between strong and weak expression of Nrf2 and Keap1. After adjusting for stage and statin use, the results were similar. Statin non-users with strong MnSOD expression had better PFS compared to statin users which proves that statins have impact on redox-state regulating enzymes. However, these findings are preliminary and require further research.

Comparative efficacy of Bacillus Calmette-Guérin instillation and radical cystectomy treatments for high-risk non-muscle-invasive urothelial cancer classified as high-grade T1 in initial and repeat transurethral resection of bladder tumor.

To compare the differential therapeutic effects of Bacillus Calmette-Guérin (BCG) instillation and radical cystectomy (RC) for high-risk non-muscle-invasive urothelial cancer (NMIBC) classified as high-grade T1 in initial and repeat transurethral resection of bladder tumors (TURBT) and to construct a prediction model. We retrospectively analyzed the clinical data of patients with malignant bladder tumors treated at the First Affiliated Hospital of Soochow University from January 2016 to December 2017 and compared the differences in 1-year, 2-year, 3-year, 5-year, and comprehensive overall survival (OS) and progression-free survival (PFS) between BCG instillation treatment and RC treatment. Survival curves were drawn to show differences in OS and PFS between the two groups. Concurrently, univariate and multivariate COX analyses were performed to identify risk factors affecting OS and PFS, and a nomogram was created. In total, 146 patients were included in the study, of whom 97 and 49 were in the BCG and RC groups, respectively. No statistical differences were observed in the 1- and 2-year OS and PFS between the two groups, whereas significant statistical differences were found in the 3-year, 5-year, and comprehensive OS and PFS. Survival curves also confirmed the statistical differences in OS and PFS between the BCG and RC groups. Multivariate COX analysis revealed that the treatment method, concomitant satellite lesions, and albumin-to-alkaline phosphatase ratio (AAPR) were independent risk factors affecting OS and PFS. The nomogram that was further plotted showed good predictive ability for OS and PFS. For patients who exhibit high-level T1 pathology after both initial and repeat TURBT, especially those with low AAPR, and concomitant satellite lesions, choosing RC as a treatment method offers a better prognosis.

Weekly Versus Bolus Cisplatin Concurrent With Definitive Radiation Therapy for Squamous Carcinoma of the Head and Neck: A Systematic Review and Network Meta-Analysis

The schedule of cisplatin concurrent with definitive radiation for squamous carcinoma of the head and neck remains controversial. Most institutions deliver either a high-dose "bolus" schedule once every 3 weeks or a low-dose weekly schedule. We compared these 2 schedules via a simplified network meta-analysis with a common comparator. We performed a PRISMA-concordant systematic review to identify randomized controlled trials comparing cisplatin with cetuximab for nonmetastatic, locoregionally advanced squamous carcinoma of the head and neck treated with definitive radiation. Trials incorporating primary surgery or induction therapy were excluded. Patient survival times were extracted on a per-event basis from the published curves using a digitizer and validated against published point estimates and hazard ratios (HRs). Survival was compared using random effects Cox regression under a frequentist framework. Toxicity and secondary endpoints were analyzed qualitatively. The Cochrane method assessed the risk of bias. The analysis plan was preregistered with the Open Science Foundation. Five randomized trials were identified, including 1678 patients. There was no statistical difference in overall survival between weekly and bolus regimens (HR, 0.90; 95% CI, 0.53-1.52, P = .345). This Cox model suggested that for the average patient in the cohort, the absolute difference in 5-year overall survival between weekly and bolus regimens was +1.2% (95% CI, -6.1%-+5.9%, P = .345). Secondary endpoints and toxicity were not obviously different by regimen, qualitatively. The cetuximab trials provide indirect data suggesting that the differences between cisplatin schedules are subtle.

Five-year survival outcomes from the PIT-1 trial: Pemetrexed-cisplatin plus bevacizumab or concurrent thoracic radiation therapy followed by surgery in stage IIIA (N2) nonsquamous non-small cell lung cancer.

8064 Background: Personized Induction Therapy-1 (PIT-1) is a multicenter, randomized phase II selection design trial of pemetrexed-cisplatin plus bevacizumab (BEV arm) or concurrent thoracic radiation therapy (TRT arm) followed by surgery in patients with stage IIIA (N2) nonsquamous non-small cell lung cancer (NSCLC). The TRT arm was chosen as the investigational induction treatment strategy for a future phase III study based on the results of a numerically higher 2-year progression-free survival (PFS, primary endpoint) in the TRT arm and fatal postoperative complications observed only in the BEV arm. We report updated, exploratory analyses of survival, approximately 5 years after the last patient was randomly assigned. Methods: Patients with stage IIIA (N2) nonsquamous NSCLC were randomly assigned (1:1) induction therapy consisting of pemetrexed and cisplatin plus bevacizumab (n = 44) or concurrent TRT (n = 44) followed by surgery. Among them, 38 patients in the BEV arm and 37 patients in the TRT arm underwent surgery. Five-year overall survival (OS), 5-year PFS, and patterns of postoperative recurrence were compared between arms. Prognostic factors of OS were analyzed in surgically resected patients using Cox’s proportional hazard model. Results: The median follow-up was 66.4 months. In 82 treated patients, the 5-year OS and PFS rates were 63.5% (95% CI: 46.9-76.1) and 26.2% (95% CI: 14.1-40.0) in the BEV arm (n = 42), and 57.2% (95% CI: 40.5-70.8) and 27.5% (95% CI: 14.9-41.7) in the TRT arm (n = 40), respectively. There were no statistical differences in OS ( P = 0.572) and PFS ( P = 0.356). In 75 surgically resected patients, pathological nodal down stage was the only significant prognostic factor of OS ( P = 0.014). Age, sex, smoking status, clinical T stage, clinical N stage based on a computed tomography scan, preoperative serum CEA and CYFRA level, EGFR mutation status, pathological complete response, and major pathological response did not have a significant prognostic impact on OS. The patterns of postoperative recurrence were different between arms: locoregional only, in four (11%) and one (3%); distant metastasis only, in 16 (42%) and 21 (57%); and both, in five (13%) and four (11%) in the BEV and TRT arms, respectively. The recurrence rate of ipsilateral hilar or mediastinal lymph nodes (the irradiation field) was significantly lower in the TRT arm (3%) than in the BEV arm (21%, P= 0.01). Conclusions: Five-year survival outcomes were not different between the BEV and TRT arms. The TRT arm demonstrated sufficient local control, but insufficient control of distant metastasis so this is an important issue that requires improvement in the future. Clinical trial information: s031180402.

Risk factors, impact and treatment of postoperative lymphatic leakage in children with abdominal neuroblastoma operated on by laparotomy

BackgroundLymphatic leakage is one of the postoperative complications of neuroblastoma. The purpose of this study is to summarize the clinical characteristics and risk factors of lymphatic leakage and try to find effective prevention and treatment measures.MethodsA retrospective study included 186 children with abdominal neuroblastoma, including 32 children of lymphatic leakage and 154 children of non-lymphatic leakage. The clinical information, surgical data, postoperative abdominal drainage, treatment of lymphatic leakage and prognosis of the two groups were collected and analyzed.ResultsThe incidence of lymphatic leakage in this cohort was 14% (32 children). Through univariate analysis of lymphatic leakage group and non-lymphatic leakage group, we found that lymphatic leakage increased the complications, prolonged the time of abdominal drainage and hospitalization, and delayed postoperative chemotherapy (p < 0.05). In this cohort, the median follow-up time was 46 (95% CI: 44–48) months. The follow-up data of 7 children were partially missing. 147 children survived, of which 23 had tumor recurrence (5 children recurred in the surgical area). 37 children died, of which 32 had tumor recurrence (9 children recurred in the operation area). In univariate analysis, there was no statistical difference in overall survival (p = 0.21) and event-free survival (p = 0.057) between lymphatic leakage group and non-lymphatic leakage group, while 3-year cumulative incidence of local progression was higher in lymphatic leakage group (p = 0.015). However, through multivariate analysis, we found that lymphatic leakage did not affect event-free survival, overall survival and cumulative incidence of local progression in children with neuroblastoma. Resection of 5 or more lymphatic regions was an independent risk factor for lymphatic leakage after neuroblastoma surgery. All 32 children with lymphatic leakage were cured by conservative treatment without surgery. Of these, 75% (24/32) children were cured by fat-free diet or observation, 25% (8/32) children were cured by total parenteral nutrition. The median drain output at diagnosis in total parenteral nutrition group was higher than that in non-total parenteral nutrition group (p < 0.001). The cut-off value was 17.2 ml/kg/day.ConclusionsLymphatic leakage does not affect the prognosis of children with neuroblastoma, but long-term drain output caused by lymphatic leakage will still adversely affect postoperative complications and follow-up treatment, which requires attention and active treatment measures. More attention should be paid to the children with 5 or more lymphatic regions resection, and the injured lymphatic vessels should be actively found and ligated after tumor resection to reduce the postoperative lymphatic leakage. Early application of total parenteral nutrition is recommended for those who have drain output at diagnosis of greater than 17.2 ml/kg/day.Level of evidenceLevel III, Treatment study (Retrospective comparative study).

Differences in In-Hospital and Follow-Up Outcomes Between Non-A Non-B Aortic Dissection and Type B Aortic Dissection Treated by Endovascular Based Treatment.

Non-A non-B aortic dissection (AD) is a rare and life-threatening medical emergency, and it has been controversial whether it should be managed as type B aortic dissection (TBAD). The study aims to compare in-hospital and follow-up outcomes between patients with non-A non-B AD and those with TBAD treated by endovascular based treatment (EBT). From January 2017 to December 2021, 96 consecutive patients with non-A non-B AD met the inclusion criteria and underwent EBT. Patients with TBAD were matched to patients with non-A non-B AD at a 1:1 ratio using propensity score matching analysis to correct for baseline confounding factors. The primary endpoint was all-cause mortality. Aortic-related events were defined as dissection-related death, aortic rupture, retrograde type A aortic dissection, reintervention, and type Ia endoleak. Patients with non-A non-B AD required more TEVAR-related adjunctive procedures compared to TBAD patients during EBT and they required a longer ICU length of stay (36.0 vs 24.0 hours, P < .05) as well as a longer hospitalization (8.0 vs 7.0 days, P < .05) after EBT. There was no statistical difference in overall survival after EBT for patients with TBAD and non-A non-B AD. However, compared to patients with TBAD, non-A non-B AD patients had a higher rate of reintervention and experienced more aortic-related late events during follow-up. Patients with non-A non-B acute AD who are treated with EBT do not have higher in-hospital or follow-up mortality rates compared to patients with type B AD. However, there is an increased risk of reintervention and aortic-related late events after the intervention during follow-up.

Assessment of programmed death-ligand 1 expression in primary tumors and paired lymph node metastases of gastric adenocarcinoma.

Anti-programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) immunotherapy has demonstrated promising results on gastric cancer (GC). However, PD-L1 can express differently between metastatic sites and primary tumors (PT). To compare PD-L1 status in PT and matched lymph node metastases (LNM) of GC patients and to determine the correlation between the PD-L1 status and clinicopathological characteristics. We retrospectively reviewed 284 GC patients who underwent D2-gastrectomy. PD-L1 was evaluated by immunohistochemistry (clone SP142) using the combined positive score. All PD-L1+ PT staged as pN+ were also tested for PD-L1 expression in their LNM. PD-L1(-) GC with pN+ served as the comparison group. Among 284 GC patients included, 45 had PD-L1+ PT and 24 of them had pN+. For comparison, 44 PD-L1(-) cases with pN+ were included (sample loss of 4 cases). Of the PD-L1+ PT, 54.2% (13/24 cases) were also PD-L1+ in the LNM. Regarding PD-L1(-) PT, 9.1% (4/44) had PD-L1+ in the LNM. The agreement between PT and LNM had a kappa value of 0.483. Larger tumor size and moderate/severe peritumoral inflammatory response were associated with PD-L1 positivity in both sites. There was no statistical difference in overall survival for PT and LNM according to the PD-L1 status (P = 0.166 and P = 0.837, respectively). Intra-patient heterogeneity in PD-L1 expression was observed between the PT and matched LNM. This disagreement in PD-L1 status may emphasize the importance of considering different tumor sites for analyses to select patients for immunotherapy.

Survival Outcomes of Temporal Bone Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

Temporal bone squamous cell carcinoma (TBSCC) is a rare malignancy with poor prognosis, and optimal treatment for advanced cases is uncertain. Our systematic literature review aimed to assess 5-year survival outcomes for advanced TBSCC across different treatment modalities. EMBASE, Medline, PubMed, and Web of Science. A systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for articles published between January 1989 and June 2023. The review yielded 1229 citations of which 31 provided 5-year survival data for TBSCC. The final analysis included 1289 patients. T classification data was available for 1269 patients and overall stage for 1033 patients. Data for 5-year overall survival (OS) was 59.6%. Five-year OS was 81.9% for T1/2 and 47.5% for T3/4 (P < .0001). OS for T1/T2 cancers did not significantly differ between surgery and radiation (100% vs 81.3%, P = .103). For advanced-stage disease (T3/T4), there was no statistical difference in OS when comparing surgery with postoperative chemoradiotherapy (CRT) (OS 50.0%) versus surgery with postoperative radiotherapy (XRT) (OS 53.3%) versus definitive CRT (OS 58.1%, P = .767-1.000). There was not enough data to assess the role of neoadjuvant CRT. Most patients will present with advanced-stage disease, and nodal metastasis is seen in nearly 22% of patients. This study confirms the prognostic correlation of the current T classification system. Our results suggest that OS did not differ significantly between surgery and XRT for early stage disease, and combined treatment modalities yield similar 5-year OS for advanced cancers.

Acute kidney injury after radical gastrectomy: incidence, risk factors, and impact on prognosis.

Acute kidney injury (AKI) is a serious adverse event often overlooked following major abdominal surgery. While radical gastrectomy stands as the primary curative method for treating gastric cancer patients, little information exists regarding AKI post-surgery. Hence, this study aimed to ascertain the incidence rate, risk factors, and consequences of AKI among patients undergoing radical gastrectomy. This was a population-based, retrospective cohort study. The incidence of AKI was calculated. Multivariate logistic regression was used to identify independent predictors of AKI. Survival curves were plotted by using the Kaplan-Meier method and differences in survival rates between groups were analyzed by using the log-rank test. Of the 2,875 patients enrolled in this study, 61 (2.1%) developed postoperative AKI, with AKI Network 1, 2, and 3 in 50 (82.0%), 6 (9.8%), and 5 (8.2%), respectively. Of these, 49 patients had fully recovered by discharge. Risk factors for AKI after radical gastrectomy were preoperative hypertension (odds ratio [OR], 1.877; 95% CI, 1.064-3.311; P = 0.030), intraoperative blood loss (OR, 1.001; 95% CI, 1.000-1.002; P = 0.023), operation time (OR, 1.303; 95% CI, 1.030-1.649; P = 0.027), and postoperative intensive care unit (ICU) admission (OR, 4.303; 95% CI, 2.301-8.045; P < 0.001). The probability of postoperative complications, mortality during hospitalization, and length of stay in patients with AKI after surgery were significantly higher than those in patients without AKI. There was no statistical difference in overall survival (OS) rates between patients with AKI and without AKI (1-year, 3-year, 5-year overall survival rates of patients with AKI and without AKI were 93.3% vs 92.0%, 70.9% vs 73.6%, and 57.1% vs 67.1%, respectively, P = 0.137). AKI following radical gastrectomy is relatively rare and typically self-limited. AKI is linked with preoperative hypertension, intraoperative blood loss, operation time, and postoperative ICU admission. While AKI raises the likelihood of postoperative complications, it does not affect OS.

Safety and Survival Outcomes of Liver Resection following Triple Combination Conversion Therapy for Initially Unresectable Hepatocellular Carcinoma.

Triple combination conversion therapy, involving transcatheter arterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), has shown an encouraging objective response rate (ORR) and successful conversion surgery rate in initially unresectable hepatocellular carcinoma (HCC). However, the safety and long-term survival outcomes of subsequent liver resection after successful conversion still remain to be validated. From February 2019 to February 2023, 726 patients were enrolled in this retrospective study (75 patients received hepatectomy after conversion therapy [CLR group], and 651 patients underwent pure hepatectomy [LR group]). Propensity score matching (PSM) was used to balance the preoperative baseline characteristics. After PSM, 68 patients in the CLR group and 124 patients in the LR group were analyzed, and all the matching variables were well-balanced. Compared with the LR group, the CLR group experienced longer Pringle maneuver time, longer operation time, and longer hospital stays. In addition, the CLR group had significantly higher incidence rates of intra-abdominal bleeding, biliary leakage, post-hepatectomy liver failure (PHLF), and Clavien-Dindo grade IIIa complications than the LR group. There were no significant statistical differences in overall survival (OS) (hazard ratio [HR] 0.724; 95% confidence interval [CI] 0.356-1.474; p = 0.374) and recurrence-free survival (RFS) (HR 1.249; 95% CI 0.807-1.934; p = 0.374) between the two groups. Liver resection following triple combination conversion therapy in initially unresectable HCC may achieve favorable survival outcomes with manageable safety profiles; presenting as a promising treatment option for initially unresectable HCC.

End-of-Life Outcomes in Patients with Acute Myeloid Leukemia Receiving Non-Curative Chemotherapy

Background: Patients with acute myeloid leukemia (AML) frequently have poor-quality end of life (EOL) care including intensive care unit admissions and prolonged hospitalizations. Prognostic uncertainty and restrictions on transfusions during hospice are barriers that prevent patients with AML from having access to palliative care services. There is a paucity of data on EOL care on patients with AML that are unable to continue a venetoclax and hypomethylating agent (HMA-ven) treatment. Methods: A query was conducted using Northwell Cancer Institute's electronic health records to identify all transplant-ineligible patients with AML who received HMA-ven between January 2019 and December 2022 that had died. We retrospectively analyzed the charts of 84 patients who fit the criteria. EOL outcomes including rate of advanced care planning, location of death, and resource utilization were recorded. Overall survival (OS) was defined as the time from start of the last line of chemotherapy to death for patients that had disease-modifying treatment at EOL. For those that continued to best supportive care (BSC), OS was defined as the time from stopping the last dose of chemotherapy to death. Hospice length of stay (HLOS) was the time from a hospice referral to death for patients that chose to stop transfusions and pursue hospice. Kaplan-Meier method and log rank testing were used to compare time to event data. Results: In our cohort of 84 patients, 43% of patients died on hospice, 53% of patients died in the hospital, with 23% requiring an ICU admission at the end of life. 18% had either cardiopulmonary resuscitation (CPR) or an activation of the emergency response system within 24 hours of death. While more than half of patients opted to not have CPR, 15% of these decisions were made within the last 24 hours of life. Furthermore, of the patients only 65% saw a palliative care physician while admitted for treatment. Of note, 42 patients tolerated HMA-ven and were continued to take this medication until their death. However, 42 patients stopped HMA-Ven due to progression of disease (69%) or intolerance (31%). Of this cohort, 15 patients continued to subsequent line therapy following HMA-ven with a median OS of 56 days. 24 patients continued on to hospice without transfusion support, with a median HLOS of 7 days. Seven patients continued BSC with median OS of 41 days, requiring an average of 1.6 transfusions weekly. Of note, the patients that continued BSC did not transition to hospice as these patients were unable or unwilling to stop transfusions. There was no statistical difference in OS between receiving subsequent chemotherapy and BSC at EOL (p = 0.40). Patients receiving BSC had a lower percentage of patients dying in the ICU (55% vs 40%) and documented advanced directives with a health care proxy (29% vs 7%) compared to those that had received chemotherapy at EOL. Discussion: Our study identified opportunities to improve EOL care and goal-concordant care in patients with AML receiving non-curative therapy. A subset of this population significantly benefitted from transfusion-only support and stopping disease modifying treatment. Opting for BSC may drastically improve the EOL quality by decreasing ICU deaths and improving access to goal-concordant care. Further research on the timing of best supportive care to patients with AML undergoing non-curative intent therapy as opposed to continuing subsequent line chemotherapy regimens is needed.

The Use of 2 nd Generation TKIs As First Line Therapy Does Not Prevent CML Related Deaths: Results of an Italian CML Campus Prospective Study in 1277 Patients Treated First Line with Imatinib or 2 nd Generation TKIs

Background: In the last decades prognosis and survival of chronic myeloid leukemia (CML) patients have dramatically improved, thanks to a wider therapeutic armamentarium. Molecular responses are the milestones that guide clinical decisions; however, some information is still lacking and what we know derives mainly from investigational trials: it is still unclear if real-life management could lead to comparable results. For this reason, a prospective observational study was conducted by a CML Italian network to analyze molecular responses in a real-life setting. Methods: A web-based database (www.epiclin.it/lmc) was used to collect clinical and biological data on newly diagnosed CML prospective consecutive patients enrolled in 24 Italian Hematology Centers from January 2013 onwards. Patients were treated according to the policy of the center and the molecular data were obtained by performing tests in accordance with the IS% parameters. Results: A total of 1277 patients were enrolled (Tab. 1) with a median follow up of 4,1 years. There was a significant difference in the median age of patients who started with imatinib (IMA) or 2 nd gen TKIs (II-TKI): 70 vs 52, respectively. The Overall Survival (OS) of the whole cohort at 5 years was 80% for the IMA and 94% for II-TKI treated patients respectively. Out of the total 86 deaths observed in the IMA treated cohort only 11 (12.7%) were due to CML related causes, whereas out of the 32 deaths observed in the II-TKI treated cohort 12 (37.5%) were due to CML. Out of the 607 patients who were on first line IMA, 422/607 (69%) did not switch therapy and have an OS of 81% at 5 years. One hundred and eighty-five out of 607 (31%) changed therapy and showed an OS of 80% at 5 years. Out of 670 patients who started with II-TKI, 492 (73%) continued the same treatment and 178/670 (27%) changed therapy, showing a 5-year OS of 96% and 89%, respectively. In summary, patients who remain in the same type of therapy in which they were initially started show a 5-year OS of 81% and 96% for IMA and II-TKI respectively and only 9 of the total 73 deaths observed in this group of 914 patients were CML related (8 of 58 II-TKI treated patients). Patients who switched to another therapy showed 80% and 89% 5-year OS on IMA and II-TKI group, respectively. Of the 45 deaths observed in this group of 363 patients, 14 were CML related (3 on IMA and 11 on II-TKI) (Tab. 2). In IMA treated patients, 5-year OS according to 6- and 12-months molecular response was worse for patients with BCR::ABL1 &amp;gt;1% compared to those with values between 1 and 0.1% and &amp;lt;0.1% BCR::ABL1 patients (looking at 12 months response, OS was 65% vs 85% vs 90%, Fig. 1A). At 24 months there was a statistical difference in OS between patients with BCR::ABL1 between 1 and 0.1% versus those &amp;lt;0.1% (OS at 3 years was 82% vs 92%) (Fig. 1B). Among II-TKI treated patients, no significant differences in OS were observed, but there was only a generic trend for those with deeper molecular responses between patients with BCR::ABL1 &amp;gt;0.1 versus patients with BCR::ABL1 &amp;lt; 0.1% at all timepoints; to note, the deaths are few and were observed within the first year, independently from the molecular response achieved: at 6 months, 10 deaths on 113 patients of which 7 CML related; at 12 months, 5 deaths on 48 patients of which 4 CML related. Row comparisons of OS were confirmed with multivariable Cox models including main prognostic factors. Conclusions: The real-life data collected by this observational study support the good prognosis of CML patients obtained in our days independently by the TKI used in first line. Indeed, most of the deaths observed are due to CML unrelated causes and the use of II-TKIs does not seem to prevent the CML related deaths, whose number is similar in both cohorts. The fact that the OS is similar in those who remain in IMA therapy versus to those who switch could also simply reflect the presence of unfavorable prognostic factors at diagnosis not controlled by IMA nor by II-TKIs. In this scenario, the observation that the achievement of &amp;lt;1% at 12 months and of MMR at 24 months in patients treated with imatinib is endowed with a statistically significant better OS could simply represent an association rather than a determining factor. Early NGS study would probably provide helpful information at this regard and for identifying patients that, even if treated first line with II-TKIs, could benefit of an early switch, since 11 of the 12 progressions were observed in this group.

Comparative Study of Male and Female Patients Undergoing Frozen Elephant Trunk Total Arch Replacement.

Our aim was to investigate outcomes and long-term survival in male and female patients after frozen elephant trunk (FET) total arch replacement. Between March 2013 and January 2023, 362 patients underwent aortic arch replacement via the FET technique. We compared patient characteristics and intra- and postoperative data between male and female patients. Male patients were significantly younger (p = 0.012) but revealed a higher incidence of coronary artery disease (p = 0.008) and preoperative dialysis (p = 0.017). More male patients presented with type A aortic dissections (p = 0.042) while more female patients had aortic aneurysms (p = 0.025). The aortic root was replaced in significantly more male patients (p = 0.013), resulting in significantly longer cardiopulmonary bypass duration (p < 0.001) and operative times (p < 0.001). There were no statistically significant differences in postoperative outcome parameters including in-hospital mortality (p = 0.346). However, new in-stent thrombus formation was significantly more frequent in female patients (p = 0.002). Age in years (odds ratio (OR): 1.026, p = 0.049), an acute pathology (OR: 1.941, p = 0.031) and preoperative dialyses (OR: 3.499, p = 0.010) were predictive for long-term mortality in our Cox regression model, sex (p = 0.466) was not. There was no statistical difference in overall survival (log rank: p = 0.425). Female patients are older but reveal fewer cardiovascular risk factors; aneurysms are more common in female than male patients. As female patients undergo concomitant surgical procedures less often, their operative times are shorter. While survival and outcomes were similar, female patients suffered from postoperative new in-stent thrombus formation significantly more often.

Retrospective analysis of the impact of dose delay and reduction on outcomes of colorectal cancer patients treated with FOLFIRI‑based treatment.

To determine the relationship between chemotherapy dose delay/reduction with progression-free survival (PFS) and overall survival (OS) in colorectal cancer patients treated with FOLFIRI based first-line chemotherapy in real-world retrospectively study. We identified 144 eligible patients with advanced CRC who received FOLFIRI as first-line based treatment. The study protocol was submitted to the institutional review board and was exempted. Dose delay was defined as an average delay of more than 3 days (>3 days vs. ≤3 days) from the intended date. Dose reduction (actual dose/standard dose * 100%) ≤85% was considered as chemotherapy reduction in the chemotherapy dose relative to the standard (mg/m2) regimen for all cycles. Relative dose intensity (RDI) ≤80% was described as chemotherapy reduction. OS and PFS were measured using Kaplan-Meier and Cox proportional hazard models. There were 114 patients with chemotherapy dose delay (dose delay >3 days). PFS of patients without dose delay had better survival than patients with dose delay (p = 0.002). There were 28.47% patients treated with dose reduction of 5-Fu. PFS and OS were better in patients without 5-Fu dose reduction than in patients with 5-Fu dose reduction with p values of 0.024 and <0.001, respectively. Patients with high 5-FU RDI had better PFS than patients with low 5-FU RDI (p < 0.001). While, there was no statistical difference in OS between the two groups. Then we stratified the analysis by age. In <65 years cohort, both PFS and OS were better in patients with high 5-Fu RDI than in those with low 5-Fu RDI (p < 0.001, p = 0.005, respectively). But, in ≥65 years cohort, OS were better in patients with low 5-Fu RDI than in those with high 5-Fu RDI (p = 0.025). Moreover, both dose reduction and RDI of irinotecan had no statistically significant difference in both PFS and OS. In the advanced colorectal cancer patients who received FOLFIRI based treatment as first-line regimen, chemotherapy dose delay and reduction dose of 5-Fu were associated with worse survival, especially among patients younger than 65 years.