Overall Survival Research Articles

Event-free survival (EFS), a common endpoint in neoadjuvant/perioperative oncology trials, allows for accelerated treatment evaluation while awaiting results of overall survival (OS). However, the surrogacy of EFS for OS in muscle-invasive bladder cancer (MIBC) has yet to be established. This meta-analysis evaluated EFS as a surrogate endpoint for OS in neoadjuvant-treated MIBC. A systematic literature review identified neoadjuvant or perioperative clinical trials for MIBC reporting both EFS and OS. Treatment effect association was evaluated by assessing the association of the hazard ratio (HR) of EFS with that of OS. Survival outcome associations were evaluated by assessing the associations of survival rates and median survival times between EFS and OS, respectively. These associations were meta-analyzed using weighted linear regression. The strength of association was quantified using coefficient of determination (R2). Seven eligible trials were identified for the analysis of treatment effect association and 17 trials were included in the analyses of survival outcome associations. Strong association was observed between EFS and OS at treatment effect level (R2 = 0.80 [95% confidence interval (CI): 0.38-0.99]). Consistently, significant survival outcome associations were observed between 3-year EFS and 5-year OS (R2 = 0.80 [95% CI: 0.28-0.93]) and between median EFS time and median OS time (R2 = 0.97 [95% CI: 0.45-1.00]). EFS is strongly associated with OS in respect to treatment effects and survival outcome measures in clinical trials for MIBC following neoadjuvant treatment. EFS can be considered as a surrogate endpoint for OS when evaluating neoadjuvant treatments for MIBC.

This study aimed to evaluate temporal trends in treatment patterns for localized soft tissue sarcomas (STSs) and identify factors associated with relapse-free survival (RFS) and overall survival (OS). A retrospective cohort study was conducted using the Australian Comprehensive Cancer Outcomes and Research Database (ACCORD) and electronic health records from a high-volume sarcoma unit. Patients aged ≥18 years with grade 3, localized STS ≥5cm diagnosed between 2013 and 2023 were included. The cohort was divided into two periods (2013-2017 and 2018-2023) to assess changes in treatment practices. Kaplan-Meier and Cox proportional hazards models evaluated RFS and OS. Among 202 patients, radiation use decreased in the late period (79%vs. 64%, p = 0.03), with a trend toward increased systemic therapy (8%vs. 16%, p = 0.13). Median RFS was 19 months (95% confidence interval [CI]: 14.9-26.0), with no significant difference between periods (hazard ratio [HR] 1.30, 95% CI: 0.93-1.82, p = 0.13). Median OS was 48 months (95% CI: 38.1-62.9), also showing no difference (HR 1.20, 95% CI: 0.80-1.78, p = 0.38). Radiotherapy improved RFS (HR 0.69, 95% CI: 0.49-0.98, p = 0.04) but not OS. Systemic therapy showed no RFS or OS benefit. Exploratory analyses identified age, tumor size, FDG-PET SUVmax, site, and Sarculator risk as prognostic factors. Treatment patterns evolved over time, reflecting emerging evidence, but no significant RFS or OS differences were observed. Further research is needed, including exploring prognostic factors like elevated baseline FDG-PET SUVmax.

Cardiovascular disease (CVD) is highly prevalent and remains a cause of great morbi-mortality worldwide. Growing evidence suggests clonal hematopoiesis of indeterminate potential (CHIP) as an independent cardiovascular risk factor worsening overall survival (OS). However, actual data either comes from large population databases with heterogenous and/or poorly defined CVD or from smaller better-defined populations but with limited follow-up. We aimed to thoroughly characterize the extent and severity of coronary artery disease (CAD) and OS in CHIP-positive patients using the COROL (COROonary disease cLinico-biological determinants study) cohort which included patients undergoing coronarography and for which we now have up to 24 years of follow-up. We also evaluated if OS in CHIP-positive patients was similar depending on CAD treatment. We retrospectively analyzed data from the 2050 COROL patients included between 2000-2001 at CHU de Lille in France (mean age (standard deviation): 61 (12) years, men: 76.2%). Our primary focus was CAD lesions (% of stenosis) by coronarography, treatment (medical, angioplasty or surgery), CHIP (variant allele frequency (VAF) ≥2%, determined using a 70-gene NGS panel) and OS. Patients with no significant coronary lesion (<50%) served as controls. Statistical analysis for preliminary results included log-rank and Student analysis. Of the 1976/2050 patients that met inclusion criteria, CHIP was found in 28.5%. DNMT3a , TET2 and ASXL1 accounted for two-third of the mutated genes. Preliminary results in 1466/1976 patients showed reduced median OS in CHIP-negative patients with ≥50% lesions compared to those with <50% lesions (p=0.0007). Median OS was worse in both CHIP-positive groups with no difference according to CAD status (table 1). Moreover, no CAD treatment could reverse CHIP effect (figure 1). Our study is the first to provide detailed information on CAD extent and treatment in CHIP-positive patients while offering 20+ years of follow-up. It shows an independent negative effect of CHIP on OS, which raises concerns about CHIP identification and CAD patients management.

This study aims to assess the surgical characteristics and prognostic factors for survival outcomes of pineal region tumors (PRTs). This was a retrospective cohort study for pediatric PRTs undergoing tumor resection at Children's Hospital 2 between 2017 and 2023. Modified Rankin Scale (mRS) and Kaplan-Meier estimation were used for analyzing functional and survival outcomes. A total of 50 PRT patients were included with a median follow-up (FU) time of 34.5 months (interquartile range [IQR] 16-54.3). Histopathologies included 28% mature teratomas, 22% malignant non-germinomatous germ cell tumors (NGGCTs), 28% pineal parenchymal tumors (PPTs), and 22% gliomas. Gross-total resection (GTR) was achieved in 100% of mature teratomas compared to only 45.5% of gliomas (p = 0.02). Favorable functional outcome was 84% at 3-month and 66% at final FU. Progression-free survival (PFS) was 78% at 1 year and 54% at 5 years. Overall survival (OS) was 86% at 1 year and 76% at 5 years. Histopathology and permanent morbidity significantly influenced survival outcomes (PFS, p < 0.001; OS, p = 0.03; p < 0.001), while the extent of resection (EOR) had no substantial impact on these (PFS, p = 0.45; OS, p = 0.46). Surgical resection plays a crucial role in certain pediatric PRTs with acceptable morbidity and mortality. A higher GTR rate can be achieved in benign lesions, particularly in mature teratomas. Functional outcome improves favorably but declines thereafter due to the progression of malignant diseases. Prognostic factors for survival outcomes include histopathology and permanent morbidity regardless of EOR.

Introduction: AL cardiac amyloidosis (AL-CA) is associated with poor prognosis, largely driven by cardiac involvement. The revised Mayo staging system utilizes cardiac biomarkers to risk-stratify and predict outcomes for these patients. However, its long-term predictive value remains uncertain, particularly in the era of novel therapies. This study evaluated the prognostic impact of the revised Mayo staging system, especially on five- and ten-year survival outcomes in AL-CA patients. Methods: We conducted a retrospective cohort study of patients diagnosed with AL-CA at our quaternary center between January 2012 and December 2022. Non-AL amyloidosis patients and those lacking complete data were excluded. Overall survival (OS) was defined from the date of diagnosis until death. Cox regression evaluated associations between Mayo staging and survival. Results: Of 411 patients included, 63.7% were male, 78.6% white, with a median age at AL-CA diagnosis of 68 years (IQR: 31–92). Mayo staging distribution was: stage I (3.6%), stage II (12%), stage III (27.7%), and stage IV (55.5%). During a median follow-up of 25.7 months (IQR: 4.7,56.2), 60.8% (n=250) of patients died. Survival differed significantly by Mayo stage, with a median OS of 80.2 months in stage II, 47.2 months in stage III, and 12.8 months in stage IV (log-rank p &lt; 0.0001) (Figure 1). On multivariable Cox regression, increasing age was independently associated with worse survival (HR = 1.02, 95% CI: 1.01–1.04, p&lt;0.001). Compared to Mayo stage I/II, stage III (HR = 2.02, p=0.005) and stage IV (HR = 2.98, p&lt;0.001) were associated with significantly higher mortality. NYHA class IV was also independently associated with increased risk of death (HR = 1.77, p=0.035) (Figure 2) (Table 1) Long-term follow-up indicated that the 5-year OS was 53.6% (stage I), 73.3% (stage II), 45.5% (stage III), and 32.8% (stage IV). Ten-year OS was 53.6% (stage I), 47.1% (stage II), 23.9% (stage III), and 22.1% (stage IV). Notably, 67% of stage IV survivors at five years remained alive at ten years, comparable to stage II (64%). Conclusion: The revised Mayo staging remains prognostic for AL-CA, demonstrating significant stage-based survival differences. Despite improved outcomes with contemporary treatments, advanced-stage disease remains associated with poorer survival. Importantly, patients in higher-risk stages who reach the five-year mark maintain a substantial likelihood of long-term survival similar to those with less severe stages

Asparaginase is a cornerstone of pediatric acute lymphoblastic leukemia (ALL) therapy, but treatment discontinuation due to toxicity may increase relapse risk and compromise outcomes. We retrospectively analyzed 993 pediatric ALL patients (aged 1.0-17.9 years) treated under the CCCG-ALL-2015 protocol from May 2015 to October 2020. Patients were followed from the last administered asparaginase dose until relapse, death, secondary malignancy (SMN), or end of follow-up (median: 6.0 years). Asparaginase was truncated in 40 (4.0%) patients, primarily due to hypersensitivity or pancreatitis. Compared to non-truncated patients (n = 953), truncated patients had a higher 6-year cumulative incidence of relapse (CIR: 31.5% vs. 17.5%, HR: 2.01, P = .038), as well as inferior event-free survival (EFS) (HR: 2.11, P = .015) and overall survival (OS) (HR: 2.74, P = .046). CIR was also significantly higher among patients receiving < 53% of planned asparaginase doses (32.1% vs. 14.0%, HR: 2.71, P = .004). In intermediate-risk subgroup, truncation was associated with significantly reduced EFS (HR: 1.95, P = .046). Older age (≥ 10 years), higher MRD levels (day 19 ≥ 0.1%), and higher asparaginase exposure percentage were predictors of discontinuation. In conclusion, asparaginase discontinuation is associated with inferior outcomes, emphasizing the importance of replacement with alternative formulations to maintain treatment intensity.

Introduction: Venetoclax, a BCL-2 antagonist, is a novel anti-neoplastic agent used in various hematologic malignancies, including acute myeloid leukemia (AML). The aim of the current study is to evaluate the incidence, risk factors, and outcome of cardiovascular adverse events among newly diagnosed AML patients receiving venetoclax-based therapy. Methods: We conducted a retrospective, single-center cohort study of 214 patients with newly diagnosed AML who were treated with venetoclax and hypomethylating agents between August 2022 and October 2024. Inclusion criteria were newly diagnosed AML (de-novo, secondary [sAML], or treatment-related [tAML]). Major adverse cardiovascular event (MACE) was defined as new-onset heart failure (HF), HF exacerbation, coronary artery disease requiring intervention, or stroke during active venetoclax treatment. We modeled overall survival (OS) using multivariable Cox proportional hazard analysis with MACE as a time-dependent variable, and we adjusted for age, sex, AML subtype, and European LeukemiaNet (ELN) 2024 risk classification. Results: Among the 214 patients (91 de novo AML and 123 sAML or tAML), 14 (6.5%) developed a MACE during active venetoclax-based treatment. New-onset HF represented the majority of MACE (10/14). MACEs were more common in sAML or tAML, compared to de-novo AML (85.7% vs. 14.3%; p = 0.053). In multivariable Cox proportional hazard analysis, time-dependent MACE was independently associated with inferior OS (adjusted HR 3.5; 95% CI: 2.13–5.80) after adjusting for age, sex, AML category, and ELN 2024 classification. Conclusion: Venetoclax-associated MACE is relatively common in AML patients, especially those with sAML or tAML (12/123; 9.8%). The increased risk of MACE from venetoclax in this population could be through exposure to prior chemotherapies. Our novel findings linking MACE and inferior OS highlight the need for proactive cardiovascular risk assessment and monitoring, especially in the sAML/ tAML group. Prospective longitudinal studies, including comprehensive baseline cardiovascular assessment and echocardiogram-based surveillance, may be needed for validation of our findings and further risk stratification of these patients.

Introduction: Transcatheter mitral valve replacement (TMVR) offers a less invasive alternative to traditional open-heart surgery for patients with mitral valve disease. Despite its growing use, there has been limited research on the post-procedural stratification of patients undergoing TMVR, particularly in relation to non-cardiac surgery (NCS). Methods: Data was retrospectively collected from the US-based TriNetX network, which includes 120 million patients across 70+ healthcare organizations. We identified patients aged ≥50 who underwent TMVR between 2014 and 2025, excluding those with concomitant aortic replacements. Patients were divided into two cohorts: those who underwent NCS and those who did not. A 1:1 propensity score matching (PSM) was performed based on demographics and comorbidities. Hazard ratios were used to assess overall survival (OS) and outcomes at 1 and 3 years. Results: We identified 789 patients aged 50 and above who underwent TMVR exclusively. After matching, each cohort included 152 patients. Cohort characteristics before and after matching are presented in Table 1. The group that underwent NCS exhibited significantly worse OS at both 1 year (hazard ratio [HR], 2.40 [95% CI, 1.30-4.42]) and 3 years (HR, 2.21 [95% CI, 1.37-3.57]). Additionally, readmission rates were notably higher in the NCS at 1 year (HR, 2.96 [95% CI, 1.89-4.66]) and 3 years (HR, 2.71 [95% CI, 1.79-4.12]). Gastrointestinal bleeding was also significantly more frequent in the NCS cohort at both 1 year (HR, 7.74 [95% CI, 3.28-18.28]) and 3 years (HR, 4.98 [95% CI, 2.57- 9.64]). The risk of acute kidney injury (AKI) was elevated in the NCS group at 1 year (HR, 4.69 [95% CI, 2.61-8.46]) and 3 years (HR, 4.28 [95% CI, 2.56-7.15]). However, there were no significant differences between groups regarding stroke or new-onset atrial fibrillation. Conclusion: Patients who underwent NCS following TMVR experienced significantly worse outcomes compared to those who did not. These patients had higher risks of mortality, readmission, gastrointestinal bleeding, and AKI at both 1- and 3-year post-procedure. Patients undergoing TMVR who undergo NCS appear to be a particularly high-risk group and may benefit from targeted therapies and meticulous postoperative care.

Pancreatic ductal adenocarcinoma (PDAC) lacks consistent biomarkers to monitor treatment response and predict survival. Metabolically active extracellular vesicles (EVs) carrying tumor-specific KRAS mutations offer promise as disease-specific biomarkers. Informed by genomic profiling of tumor tissue, plasma samples were prospectively collected from 44 patients, with confirmed KRAS-mutated PDAC, undergoing neoadjuvant therapy (NAT) followed by surgery between 2019 and 2021. Samples were obtained at diagnosis, post-NAT, and 1month post surgery. EVs were isolated using lipid nanoprobe technology, and EV-associated KRAS mutations were detected using droplet digital polymerase chain reaction (ddPCR). Patients were grouped on the basis of temporal changes in EV-associated KRAS mutation allele frequency (MAF): no KRAS detected (ND), decreasing MAF (DD), and increasing MAF (ID). Among 44 patients, 29 (65.9%) were ND, 8 (18.2%) DD, and 7 (15.9%) ID. Detectable EV-associated KRAS MAF was found in 21%, 30%, and 50% of patients with stages I, II, and III PDAC. No significant differences were noted in demographic or clinical variables (p > 0.05). The ND group had the longest restricted mean disease-free survival (rmDFS: 31.2months), followed by DD (27.8months) and ID (9.8months; p = 0.010). Similarly, restricted mean overall survival (rmOS) was longest in the ND (40.3months), followed by DD (35.7months) and ID (17.7months; p = 0.012). On multivariable analysis, increasing EV-KRAS MAF (ID group) independently predicted inferior rmDFS [hazard ratio (HR): 6.14; p = 0.001] and rmOS (HR: 6.95; p = 0.002). Temporal increase of EV-KRAS MAF is a significant predictor of reduced DFS and OS in PDAC. Integrating EV-KRAS mutation allele frequency dynamics analysis with current biomarkers such as carbohydrate antigen 19-9 (CA19-9) could improve treatment monitoring and survival prognostication.

Poly(ADP-ribose) polymerase inhibitors (PARPi) have survival benefits for patients with high-risk (High-risk disease is defined per the phase III OlympiA trial as follows: for triple-negative breast cancer, residual disease after neoadjuvant chemotherapy or node-positive or ≥2 cm tumors after adjuvant chemotherapy; for hormone receptor-positive disease, four or more positive nodes after adjuvant chemotherapy or a CPS + EG score ≥3 after incomplete response to neoadjuvant chemotherapy. The CPS + EG score accounts for clinical/pathologic stage, ER status, and grade (Giaquinto et al. in CA Cancer J Clin 72:524-541, 2022)), human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (eBC) with germline BReast CAncer gene mutations (gBRCAm). However, many patients are unaware of their gBRCA status; this can impact eligibility for targeted treatment. We sought to evaluate patient preferences for BRCA testing and treatment decision-making as they relate to HER2-negative eBC. We conducted an online survey, including a best-worst scaling exercise (BWS) and discrete-choice experiment (DCE), among patients with self-reported HER2-negative eBC residing in the USA who were either untested, unsure if they were tested, or tested positive for the gBRCAm. The BWS generated a rank ordering of 16 barriers and facilitators to BRCA testing. The DCE evaluated patient preferences for adjuvant therapies versus no treatment based on seven treatment attributes: invasive disease-free survival, targeted treatment, nausea risk, risk of serious side effects, regimen, treatment duration, and cost. BWS and DCE exercises were analyzed using hierarchical Bayesian models. Among the 359 women included in our sample, the top facilitators for BRCA testing were determining eligibility for targeted therapy that may prevent or delay metastasis, a physician's recommendation, and absence of out-of-pocket costs (OOPC). In contrast, the top barriers were an OOPC of $250, potential anxiety from test results, and the possibility of a 3- to 4-week delay in treatment. The DCE showed that most participants preferred adjuvant treatment (77.6%) over no treatment, and reducing treatment OOPC from $900 to $0, reducing the risk of serious side effects from 77 to 24%, and having a BRCA-targeted treatment influenced treatment choice most. Individuals reported that a key benefit of BRCA testing was the insight it provided into their treatment options, allowing for more personalized care. However, OOPC was a barrier to testing. Their choice to receive adjuvant therapy was most influenced by OOPC, followed by the tolerability of the treatment and the ability to receive a targeted therapy.

after androgen ablation treatment for prostate cancer, virtually all patients with recurrent or advanced disease develop castration resistance (CRPC). Abiraterone and enzalutamide are the most commonly used novel antiandrogen treatments in patients with castration-resistant prostate cancer (CRPC). The solute carrier transporter (SLCO2B1) enables various anticancer compounds or hormones to enter cells, including the adrenal androgen dehydroepiandrosterone (DHEAS), a precursor to the most potent androgen dihydroxytestosterone (DHT), which is the substrate binding and activating the androgen receptor in normal and prostate cancer (PCa) cells. Other substrates of SLCO2B1 are statins. An in vitro-part study showed that statins, by binding to SLCO2B1, can block the uptake of DHEAS competitively, decreasing the available intratumoral androgen and improving and extending the effect of primary ADT. to evaluate whether the addition of statins to the new antiandrogens (abiraterone or enzalutamide) affects overall and progression-free survival in patients with metastatic castration-resistant prostate cancer. medical records of patients with mCRPC taking abiraterone or enzalutamide between December 2019 and January 2022 were reviewed in a tertiary hospital. Patients were assessed for statin use at the time of treatment initiation, progression free (PFS) and overall survival (OS), prostate-specific antigen (PSA) variations, and other variables of interest. Statistical analysis was performed using SPSS 22.0. a total of 107 patients receiving ADT (63 abiraterone - 59.4% - and 43 enzalutamide - 40.6%) for mCRPC in this time period were eligible for inclusion in this retrospective study. Patients had a mean age of 76.5 years (48-93). 26 patients had surgery with curative intent prior to the treatment (24.5%), 19 had previous pelvic radiotherapy with curative intent (17.9%) and 20 patients (18.9%) were previously treated with chemotherapy with docetaxel. Statins use was a significant prognostic factor for longer PFS, with a mean time of 13,68 months for those who do not use statins and 19,62 months for those who do (p<0.06). No statistically significant difference was found in OS or global mortality between the patients who use or do not use statins. Statins use also did not show any difference in the reduction of PSA values during the treatment with ADT. Our study suggests a prognostic impact of statin use in the PFS in patients receiving abiraterone or enzalutamide for mCRPC. This may be related to the enhancement of the antitumor activity of the ADT drugs, but also to the cardioprotective effects associated with statin use.

BackgroundNodal metastasis in oral cavity squamous cell carcinoma (OCSCC) is associated with poorer prognosis. Limited evidence is available on the predictive factors and prognostic significance of level IV nodal metastasis. This study evaluated patient outcomes by analyzing disease-free survival (DFS) and overall survival (OS) in individuals with level IV nodal involvement.MethodsThe cohort for this retrospective study comprised all patients with node-positive OCSCC who underwent surgery between August 2011 and June 2021. The patients’ demographic and treatment details were abstracted from the electronic medical records. DFS and OS were analyzed using a log-rank test for univariate analysis and the Cox proportional hazards model for multivariate analysis.ResultsAmong the cohort of 578 node-positive patients, 27.2% exhibited level IV nodal metastasis. The two-year DFS and OS rates in the level IV nodal metastasis group were 55% and 72.2%, respectively. Patients with level IV involvement had a median age of 53 years (range: 21-85 years), were predominantly male (69.2%), and had a median follow-up of 30.1 months (range: 1-131.9 months). A significantly higher prevalence of level IV nodal metastasis was associated with pathological tumor stage 4b (pT4b) (45.3% vs. 11.7%, p < 0.01), pathological nodal stage 3b (pN3b) (30.6% vs. 29.0%, p = 0.01), larger maximum tumor size (Tmax) (3.36 cm vs. 3.42 cm, p < 0.01), and greater depth of invasion (DoI) (1.44 cm vs. 1.63 cm, p < 0.01).In univariate analysis, DFS was significantly associated with the primary site, Tmax, DoI, involved margins, lymphovascular invasion (LVI), perineural invasion (PNI), masticator space involvement, extranodal extension (ENE), and level IV nodal metastasis, in addition to pathological tumor stage (pT), pathological nodal status (pN), and overall stage. In multivariate analysis, the primary site, Tmax, involved margins, LVI, and PNI remained independently associated with DFS. For OS, univariate analysis identified the primary site, Tmax, DoI, involved margins, LVI, PNI, bone involvement, and ENE, as well as pT, pN, and overall stage, as significant predictors. Following multivariate adjustment, the primary site, Tmax, involved margins, and PNI emerged as independent predictors of OS.ConclusionThe two-year DFS and OS rates for 578 patients with node-positive OCSCC were 55% and 72.2%, respectively. Among these patients, 157 (27.2%) exhibited level IV nodal metastasis, with skip metastasis to level IV observed in only 3.2% of cases. Patients with pT4b disease, pN3b disease, larger Tmax, and greater DoI were significantly more likely to have level IV metastasis. In univariate analysis, level IV metastasis was significantly associated with worse DFS. Additionally, primary tongue tumors, larger tumor size, involved surgical margins, and the presence of LVI or PNI were predictive of poorer DFS. For OS, significant predictors included primary tongue origin, larger tumor size, positive margins, and PNI.

Invasive intraductal papillary mucinous neoplasms (I-IPMNs) are considered more indolent than conventional pancreatic ductal adenocarcinoma (PDAC). Although neoadjuvant therapy (NAT) is widely adopted in PDAC, its role in I-IPMN remains unclear. This study aimed to evaluate the impact of NAT on survival in I-IPMN compared with PDAC. The study enrolled I-IPMN and PDAC patients undergoing resection at the University of Colorado Hospital between 2013 and 2023. Prognostic factors for overall survival (OS) were identified using Cox models. OS was compared between histology/NAT subgroups using the Kaplan-Meier method and the log-rank test, stratified by resectability. Of 500 patients (413 PDAC, 87 I-IPMN), 289 PDAC and 34 I-IPMN patients received NAT, and the I-IPMN patients showed slightly longer median OS than the PDAC patients (30.2 vs 28.1 months; p = 0.04). In the entire cohort, worse OS was associated with borderline resectable (BR)/locally advanced (LA) disease, elevated cancer antigen 19-9 (CA19-9), node-positive disease, lymphovascular invasion, perineural invasion, and absence of adjuvant therapy. In the resectable cohort (n = 311), NAT was associated with longer OS in PDAC (61.9 vs 34.2 months; p < 0.001), but not in I-IPMN (not reached vs 47.9 months; p = 0.74). Survival did not differ between NAT-treated resectable I-IPMN and PDAC (p = 0.95). In the BR/LA cohort treated with NAT (n = 183), OS was similar between I-IPMN and PDAC (17.1 vs 22.0 months; p = 0.69). In resectable I-IPMN, NAT was not associated with improved survival. Comparable survival between NAT-treated BR/LA I-IPMN and PDAC suggests a need for further research on treatment outcomes.

Background This study evaluated the prognostic role of the albumin-to-fibrinogen ratio (AFR) in patients with intrahepatic cholangiocarcinoma (ICC) after curative liver resection. Methods Retrospectively analyzed the clinicopathological information of ICC patients and stratified them into two groups by AFR (8.71). A 1:3 propensity score matching (PSM) analysis was used to eliminate possible biases. Kaplan-Meier method was used for survival analysis. Independent prognostic factors for overall survival (OS) and disease-free survival (DFS) were analyzed using Cox regression analysis, and based on which two nomograms were constructed. The concordance index (C-index), decision curve analysis (DCA), calibration curve, and receiver operating characteristic (ROC) curve were used to validate the nomograms. Results 559 patients were included and were divided into low- and high-AFR groups, respectively. High-AFR group had better prognosis. The multivariate analysis revealed that AFR was an independent prognostic factor for both OS (hazard ratio [HR] 0.393, P &amp;lt; 0.001) and DFS (HR 0.538, P &amp;lt; 0.001). Two nomograms were established to predict OS and DFS, and demonstrated high predictive accuracy and clinical utility. Furthermore, ROC curves demonstrated the high predictive power of the nomogram for survival in ICC patients. Conclusions Preoperative AFR was an independent prognostic factor for postoperative OS and DFS in ICC patients, and AFR-based nomograms effectively predict postoperative survival outcomes.

On January 17, 2025, the FDA approved datopotamab deruxtecan-dlnk (DATROWAY; Dato-DXd), a Trop-2-directed antibody and topoisomerase inhibitor conjugate, for the treatment of adults with unresectable or metastatic, hormone receptor-positive, HER2-negative breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease. Approval was based on results from TROPION-Breast01 (TB01), a multicenter, randomized, open-label trial comparing Dato-DXd with investigator's choice of chemotherapy (ICC). The trial was designed with dual primary endpoints: progression-free survival assessed by blinded independent central review according to RECIST v1.1 and overall survival (OS). TB01 demonstrated a 2-month improvement in median progression-free survival for Dato-DXd compared with ICC (6.9 vs. 4.9 months, respectively; stratified HR, 0.63; 95% confidence interval, 0.52-0.76; P < 0.0001). The OS endpoint was not met; at the final analysis of OS, the median OS was 18.6 months in the Dato-DXd arm and 18.3 months in the ICC arm (HR, 1.01; 95% confidence interval, 0.83-1.22). Although there was no OS improvement, Dato-DXd was also not associated with a clear trend toward potential detriment compared with ICC. The most commonly reported adverse reactions (≥20%) with Dato-DXd were stomatitis, nausea, fatigue, alopecia, constipation, dry eye, keratitis, and vomiting. Overall, the favorable benefit-risk profile for Dato-DXd supported its approval for the intended indication.

Partial hepatectomy and thermal ablation are standard local treatments for patients with limited colorectal liver metastases (CRLM). However, as the number of metastases increases, the question arises whether local treatment is still biologically meaningful. This study evaluates the value of radical local treatment in patients with a higher number of CRLM and seeks to identify a potential threshold of diminishing benefit. Data from the prospective AmCORE Registry were used. Patients with CRLM were divided into five groups: systemic therapy alone, and local treatment for solitary, 2-4, 5-9, and ≥ 10 CRLMs. The primary outcome measure was overall survival (OS); secondary outcome measures included local- and distant progression-free survival (LTPFS, DPFS), local control (LC), length of hospital stay, complication rates, and total tumour volume. Local treatment significantly improved OS compared to systemic therapy alone (p < 0.001), with no evidence of a threshold of diminishing benefit. There were no differences in OS between the local treatment groups over a median FU of 52.9 months (95% CI, 44.0-61.8). Median OS for the systemic therapy group was 17.9 months (95% CI, 14.1-21.6). Local treatment offered favourable LTPFS and LC per-tumour for multiple CRLM. Length of hospital stay and complication rates increased with the number of treated CRLM. Median tumour volume increased with higher numbers of CRLMs but decreased in the ≥ 10 CRLMs group (p = 0.12). No upper limit was identified for the number of CRLMs treated with curative intent resection and/or ablation. This study supports the safety and efficacy of local treatment for patients with high numbers of CRLMs.

Background Emerging evidence suggests a correlation between the platelet-to-lymphocyte ratio (PLR) and the prognosis in patients with colorectal cancer (CRC) undergoing chemotherapy. Nevertheless, the existing findings remain contentious. Methods An extensive literature review was carried out using PubMed, Embase, Web of Science, and the Cochrane Library up to February 20, 2025, to identify relevant studies on the prognostic role of PLR in clinical outcomes. We applied a set of predefined criteria to determine which studies qualified for inclusion. We assessed overall survival (OS), progression-free survival (PFS), and cancer-specific survival (CSS) using hazard ratios (HR) and corresponding 95% confidence intervals (CI). Results Our analysis included nineteen studies (26 comparative groups), involving 4,422 individuals. Aggregate data revealed a significant correlation between PLR values and both OS and PFS in CRC patients receiving chemotherapy (OS: HR = 1.18, 95% CI: 1.03–1.35; p = 0.02; PFS: HR = 1.28, 95% CI: 1.03–1.60; p = 0.03). Specifically, higher PLR values were associated with shorter OS and PFS. This association was observed across varying sample sizes, population characteristics, cut-off values, regions, treatments, and patient ages. However, no significant correlation was found between PLR values and CSS in CRC patients receiving chemotherapy (CSS: HR = 1.27, 95% CI: 0.76–2.10; p = 0.36). Conclusion Higher PLR values are significantly associated with shorter OS and PFS in CRC patients undergoing chemotherapy. However, the analysis did not demonstrate a statistically significant relationship between PLR and CSS in this patient population. In patients with CRC, PLR may serve as a useful marker for predicting outcomes and shaping individualized therapeutic approaches, especially in the context of immunotherapy. Systematic review registration https://www.crd.york.ac.uk/prospero/ , identifier CRD420251031290.

Primary objective was to evaluate the association between post-surgical MRD detected by a tumor-informed personalized panel (brPROPHET) and CRC recurrence, Secondary objectives were to determine the optimal timepoint for MRD assessment, and compare the performance of different MRD detection methods, including brPROPHET, a tumor-informed fixed panel (TIFP) and a tumor-naïve fixed panel (TNFP). Circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) has emerged as a pivotal marker in colorectal cancer (CRC), but optimal detection timing and methods remain unclear. This study included patients with resectable stage I-IV CRC. Tumor tissues were obtained at surgery, and blood samples were collected preoperatively, on post-surgical days 7 and 30 (D7/D30), and every 3-6 months. MRD was assessed using the above three methods. A total of 214 patients were included in the analysis, with imaging follow-up available for 196 patients (median follow-up: 18.2 months), among whom 24 (12.2%) experienced recurrence. MRD positivity at D7/D30 associated with significantly reduced disease-free survival (DFS). Longitudinal ctDNA-MRD positivity and MTM levels >0.01/mL were also associated with recurrence. Adjuvant chemotherapy was associated with better DFS in patients with positive MRD at D7 (HR=0.26, 95% CI 0.07-0.98, P=0.03) instead of those with negative MRD at D7. Among the 168 patients assessed with all three methods, the brPROPHET assay demonstrated better association of DFS at D7. ctDNA-based MRD detected by brPROPHET associates with recurrence in CRC. Day 7 is an effective alternative landmark to Day 30 for MRD assessment and brPROPHET outperforms TIFP and TNFP in the association of DFS. ClinicalTrials.gov number: NCT06143644.

ABSTRACTBackground and AimsThe phase II REPLACEMENT study showed promising clinical benefit from atezolizumab plus bevacizumab in transcatheter arterial chemoembolization (TACE)–naïve patients with intermediate‐stage hepatocellular carcinoma (HCC) beyond up‐to‐7 criteria, meeting its primary endpoint of progression‐free survival (PFS). Here, we report the final overall survival (OS) analysis.MethodsEnrolled patients were naïve to TACE with unresectable intermediate‐stage HCC beyond up‐to‐7 criteria, had Child‐Pugh A, Eastern Cooperative Oncology Group performance status 0/1 and received no previous systemic therapy. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered every 3 weeks. The primary endpoint was the 6‐month PFS rate by modified Response Evaluation Criteria in Solid Tumours for HCC (mRECIST); secondary endpoints included OS, PFS by RECIST version 1.1, objective response rate (ORR) and safety.ResultsOverall, 74 patients were enrolled between December 2020 and September 2021. At the clinical cut‐off date (March 31, 2024), median follow‐up was 33.6 months. Median PFS by mRECIST was 9.1 months (95% CI 7.1–10.2). Median OS was 33.8 months (95% CI 22.6–not estimable). ORR was 40.5% (95% CI 29.3–52.6), with 12.2% of patients having a complete response. Overall, 82.4% of patients received subsequent therapy. All‐cause adverse events (AEs) were observed in 98.6% of patients, most commonly hypertension (71.6%) and proteinuria (54.1%). Grade 3/4 AEs occurred in 43.2% of patients; no Grade 5 AEs were reported.ConclusionsThese results show that atezolizumab plus bevacizumab can be an alternative treatment option for patients with intermediate‐stage HCC beyond up‐to‐7 criteria who are deemed unsuitable for TACE.Trial RegistrationjRCTs071200051

Diffuse large B-cell lymphoma (DLBCL) patients with co-expression of MYC (≥ 40%) and BCL2 (≥ 50%), classified as double-expressor DLBCL (DE-DLBCL), consistently exhibit poor prognosis with traditional first-line therapies. In order to address the unmet therapeutic needs in this high-risk population, this real-world study retrospectively reviewd 46 newly diagnosed DE-DLBCL patients from two centers to evaluate the efficacy and safety of zanubrutinib-based regimens. Key outcomes included complete response rate (CRR), objective response rates (ORR), progression-free survival (PFS), overall survival (OS) and adverse events. Univariate analysis was conducted to evaluate the impact of various prognostic factors on complete response. The median age was 57.8 years (range:20-81), with 45.65% of patients over 60 years old and 17.39% over 75 years old. Advanced-stage (III/IV) disease was present in 60.87% of patients at diagnosis, 78.26% had a non-germinal center B-cell (non-GCB) subtype, and 41.3% exhibited an International Prognostic Index score ≥ 3. The best CRR was 73.90% (95% CI, 58.90%-85.70%), and the best ORR was 95.70% (95% CI, 85.20%-99.50%). At a median follow-up of 15.7 months, the 3-year PFS and OS was 86.27% (95% CI, 75.37%-98.75%) and 89.79% (95% CI, 78.40%-100%) respectively. Multivariate analysis revealed that zanubrutinib-based chemotherapy regimen significantly improved CRR. Significant differences in PFS were observed across age, bulky disease, IPI score, and extranodal involvement stratification. Adverse events were mainly hematologic toxicities and fatigue. These findings suggest that zanubrutinib may serve as an effective component of first-line therapy for this population, with favorable tolerability.