Post-progression Survival Research Articles

Immune checkpoint inhibitor plus tyrosine kinase inhibitor with or without transarterial chemoembolization for unresectable hepatocellular carcinoma

Background and aimsTranscatheter arterial chemoembolization (TACE) has been combined with immune checkpoint inhibitor (ICI)-based systemic therapies for unresectable hepatocellular carcinoma (uHCC) with promising efficacy. However, whether the addition of TACE to the combination of ICI and tyrosine kinase inhibitor (TKI) (ICI+TKI+TACE) is superior to ICI+TKI combination therapy is still not clear. Thus, this study compares the efficacy of ICI+TKI+TACE triple therapy and ICI+TKI doublet therapy in patients with uHCC.MethodsuHCC patients treated with either ICI+TKI+TACE triple therapy or ICI+TKI doublet therapy were retrospectively recruited between January 2016 and December 2021 at Eastern Hepatobiliary Surgery Hospital. The patients from ICI+TKI+TACE group and ICI+TKI group were further subjected to propensity score matching (PSM). The primary outcome was progression-free survival (PFS). The secondary outcomes were overall survival (OS) and objective response rate (ORR). Post-progression survival (PPS) as well as treatment-related adverse events (TRAEs) were also assessed.ResultsA total of 120 patients were matched. The median PFS was 8.4 months in ICI+TKI+TACE triple therapy group versus 6.6 months in ICI+TKI doublet therapy group (HR 0.72, 95%CI 0.48-1.08; p=0.115). Similar results were obtained in term of OS (26.9 versus 24.2 months, HR 0.88, 95% CI 0.51-1.52; p=0.670). The ORR in the triple therapy group was comparable with that in the doublet therapy group (16.6% versus 21.6%, p=0.487). Further subgroup analysis for PFS illustrated that patients without previous locoregional treatment (preLRT) (10.5 versus 3.7 months, HR 0.35 [0.16-0.76]; p=0.009), without previous treatment (10.5 versus 3.5 months, HR 0.34 [0.14-0.81]; p=0.015) or treated with lenvatinib (14.8 versus 6.9 months, HR 0.52 [0.31-0.87]; p=0.013) can significantly benefit from triple therapy compared with doublet therapy. A remarkable interaction between treatment and preLRT (p=0.049) or TKIs-combined (p=0.005) was also detected in term of PFS. Post progression treatment significantly improved PPS in both groups. The incidence of TRAEs was comparable between two groups.ConclusionsThe addition of TACE to ICI+TKI combination therapy did not result in a substantial improvement in efficacy and prognosis of patients. However, in selected uHCC patients (without preLRT or treated with lenvatinib as combination), ICI+TKI+TACE triple therapy may remarkably improve PFS.

Immune Checkpoint Inhibitors Affect Post-Progression Survival of Specific Patient Subgroups With Advanced Hepatocellular Carcinoma: A Study Cohorts' Analysis.

Immunotherapy-based regimens (IMBs), compared with tyrosine-kinase inhibitors (TKIs), improve the overall survival (OS) of patients with advanced hepatocellular carcinoma (aHCC). The aim of the study was to explore the interaction of prognostic factors with survival in study cohorts receiving IMB or TKI. A systematic search was performed and single arms of phase III trials including IMB or TKI were selected. Analysis of IMB and TKI cohorts was performed, and the relationship between progression-free survival (PFS) with OS was assessed. Finally, 13 variables were extracted, and their relationships with survival in the two groups were evaluated. Thirty-three study cohorts were selected. Longer OS and post-progression survival (PPS) were evident in the group of IMB, while the relationship of PFS with OS was significant only in the TKI cohorts (β = 0.527, p = 0.007). Prognostic factors in the IMB cohorts did not report any significant relationship with OS, while among patients receiving TKIs, longer OS was documented with elder age (β = 0.577, p = 0.003) and good performance status (β = 0.500, p = 0.011). Conversely, in the IMB cohorts, PPS increased with hepatitis B virus (HBV) (β = 0.756, p = 0.030) and Barcelona Clinic Liver Classification (BCLC) stage (β = 0.898, p = 0.002). In contrast to TKIs, IMBs improved the outcome of patients with aHCC by increasing PPS, particularly in patients with BCLC stage C and HBV-related hepatopathy, but the outcome improvement was lost in patients with hepatitis C virus-related liver disease.

Cachexia is an independent predictor of mortality in patients with hepatocellular carcinoma on systemic targeted therapy.

Cachexia is an independent predictor of mortality in patients with hepatocellular carcinoma on systemic targeted therapy.

ATHENA-MONO Post-Progression Survival Data Update In Patients With Newly Diagnosed Advanced Ovarian Cancer

ATHENA-MONO Post-Progression Survival Data Update In Patients With Newly Diagnosed Advanced Ovarian Cancer

Longitudinal blood immune-inflammatory and radiomic profiling to decode different patterns of acquired resistance to immunotherapy in patients with NSCLC.

To uncover the underpinnings of acquired resistance (AR) to immunotherapy (IO), we determined whether distinctive clinico-pathological, radiomic and peripheral blood (PB) immune-inflammatory features reflect oligo- and systemic (sys)-AR in advanced NSCLC patients undergoing immune checkpoints inhibitors. On 105 consecutive IO-treated advanced NSCLC, PB immunophenotypes, cytokines and CT-derived radiomic features (RFs), extracted from primary and merged metastatic lesions, were prospectively collected at baseline (T0) and first disease assessment (T1, 9-12 weeks), and their delta (Δ) variation [(T1-T0)/T0] computed. AR, defined as progression after initial response (complete/partial) or stable disease ≥ 6 months, was subdivided according to the number of new and/or progressive lesions in oligoAR (≤3) and sysAR (>3). Clinico-pathological, PB and radiomic parameters and survival outcome were statistically correlated to AR patterns. OligoAR and sysAR involved 24% and 12.4% of cases, respectively. While baseline PB immune profiles were comparable, a Δpos cytotoxic (NK, CD8+GnzB+) and Δneg immunosuppressive (CD14+ monocytes) dynamic coupled with different modulation of IL-6, TGF-β1, TNFα and sPD-L1 represented distinctive features of oligoAR vs sysAR (P<0.05). Significantly longer post-progression survival characterized oligoAR vs sysAR (median 20.3 vs 5.6 months;HR:0.22,P<0.001). The number and sites of oligoAR involvement appeared to condition blood immune background (P<0.05) and survival. Delta radiomic outperformed baseline RFs, with 15 ΔRFs sharply discriminating oligoAR from sysAR (P range:<0.001-0.04). ROC analysis confirmed the optimal performance of top-ranked ΔRFs (AUC range:0.88-0.99). Longitudinal analysis of blood immune hallmarks and radiomic descriptors may decipher distinct patterns of AR to IO in advanced NSCLC patients.

Bevacizumab exerts dose-dependent risk for intracranial hemorrhage in patients with malignant gliomas.

Bevacizumab, an anti-VEGF monoclonal antibody, has become a mainstay therapeutic in the management of malignant glioma. It is unknown if the risk of intracranial hemorrhage (ICH), a major complication associated with bevacizumab use, is dose-dependent. This was a single institution retrospective analysis of patients treated with bevacizumab for the management of gliomas between 2009 and 2022. Incidence rates of ICH between patients receiving low-dose (< 5mg/kg/week) and conventional-dose (5mg/kg/week) bevacizumab regimens were compared via competing risk analysis over time. We evaluated post-progression survival (PPS) as a secondary outcome using multivariate Cox regression. One hundred and seventy-three patients were identified (low-dose group, n = 51, conventional-dose group, n = 122) for inclusion in our analysis. Cumulative incidence rates of all cases of ICH and clinically symptomatic cases of ICH were higher in the conventional-dose (17.2% for all cases, 13.7% for symptomatic) relative to the low-dose group (3.9% for all cases, 2.0% for symptomatic); p-value 0.0296 for all cases, p-value 0.0274 for symptomatic cases. On multivariate Fine-Gray regression, conventional-dose bevacizumab therapy remained significantly associated with increased risk for symptomatic ICH (SHR 8.0560; p-value 0.0442). No difference in PPS was observed between the low-dose versus conventional-dose groups. Conventional-dose bevacizumab therapy (5mg/kg/week) is associated with increased incidence of ICH in patients with malignant glioma compared to lower dose bevacizumab (< 5mg/kg/week) in this single center retrospective cohort. No difference in PPS was observed between the low-dose versus conventional-dose groups.

The modified Glasgow Prognostic Score (mGPS) can guide decisions for immunotherapy treatment beyond progression.

The modified Glasgow Prognostic Score (mGPS) can guide decisions for immunotherapy treatment beyond progression.

Impact of re-operation on progression-free survival in patients with recurrent GBM: Experience in a tertiary referral center.

Reoperation for patients with recurrent glioblastoma multiforme (GBM) is a highly debated topic within the medical community. GBM is known for its aggressive nature and poor prognosis, with most patients experiencing tumor recurrence despite initial treatments. Some studies suggest a survival benefit from a second surgery, while others do not. The aim of this study is to assess whether reoperation for recurrent GBM offers a survival benefit compared to patients who do not undergo re-resection and to identify the prognostic factors influencing patient selection for reoperation. This study retrospectively reviewed medical records from the American University of Beirut Medical Center over a ten-year period, from 01/01/2012 to 01/01/2023. It included patients with recurrent GBM after initial surgical resection. Patients were categorized into two groups: those who underwent reoperation and those who received only medical management upon recurrence. Inclusion criteria included histologically confirmed GBM with previous tumor resection; patients who only had a biopsy were excluded. Time to progression and time to death were analyzed using the Kaplan-Meier curve, with differences between groups assessed by the log-rank test. Age categorization (≤50 vs. >50 years) and gender distribution did not significantly impact reoperation likelihood (p = 0.306 and p = 0.616, respectively). However, a notable association was observed with Charlson comorbidity index (CCI) ≤3, indicating higher reoperation rates (p = 0.022). Tumor size grouping (≤5 vs. >5 cm) showed no significant association with reoperation status (p = 0.175). Similarly, whether the tumor was unifocal or multifocal and the extent of initial tumor resection (GTR vs. subtotal) did not demonstrate significant associations with reoperation (p = 0.086 and p = 0.351, respectively). Remarkably, complications following the initial surgery emerged as a significant factor associated with the decision not to undergo reoperation (p = 0.018). The most common complications following both initial and subsequent surgeries included DVT, weakness, seizures, and wound leakage and infection. The progression-free survival for patients who underwent reoperation was 15.9 months, whereas for those who did not undergo reoperation, it was 6.7 months (log-rank p < 0.001) The median post progression survival for patients who underwent reoperation upon recurrence was 5.9 months, compared to 5.1 months for those who did not undergo reoperation. (log-rank p = 0.065). The median overall survival for patients who did not undergo reoperation was 11 months, compared to 21 months for those who underwent reoperation (log-rank p < 0.001). In conclusion, reoperation for recurrent Glioblastoma Multiforme (GBM) appears to offer a survival benefit, as indicated by significantly longer disease-free intervals and higher progression-free and overall survival rates compared to patients who did not undergo reoperation.

High levels of REV7 expression are associated with poor prognosis and chemoresistance in gastric adenocarcinoma.

REV7 is a multifunctional protein essential for promoting cellular tolerance to DNA damage. REV7 expression is associated with disease progression and prognosis in several human malignant tumors. This study aimed to evaluate the clinical and biological significance of REV7 in gastric adenocarcinoma (GAD). REV7 expression in 167 resected GADs was immunohistochemically assessed and examined the association with clinicopathological features. Positive expression of REV7 was significantly associated with tumor undifferentiation (p < 0.001), lymphatic invasion (p = 0.035), recurrence (p = 0.042), and mortality (p = 0.031). The Kaplan-Meier curves with log-rank tests revealed significantly poorer progression-free survival (p = 0.049), overall survival (p = 0.037), and post-progression survival (p = 0.038) in the REV7-positive group. Multivariate analysis using the Cox proportional hazard model identified REV7 as an independent prognostic factor for overall survival (p = 0.028). REV7-depleted GAD cell lines demonstrated enhanced sensitivity to cisplatin compared with control cells. Additionally, the expression levels of REV7 in residual tumors from surgical specimens of patients who received preoperative chemotherapy were higher than those in samples without chemotherapy (p = 0.029), suggesting that REV7-positive tumors are chemoresistant. These results indicate that REV7 is a predictive biomarker for the prognosis and chemosensitivity of GAD.

Dissection of Progressive Disease Patterns for a Modified Classification for Immunotherapy

Progressive disease (PD) in patients treated with immune checkpoint inhibitors (ICIs) varies widely in outcomes according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Efforts to modify RECIST for ICI treatment have not resolved the heterogeneity in PD patterns, posing a clinical challenge. To develop and validate a modified PD classification based on PD patterns and evaluate its association with postprogression survival (PPOS) in patients treated with the programmed cell death protein ligand 1 antibody atezolizumab across various solid tumors. This study analyzed data from 5 phase 3 trials (IMmotion151, IMvigor211, OAK, Impower133, and IMspire150) involving patients treated with atezolizumab for renal cell carcinoma (RCC), urothelial carcinoma, small cell lung cancer, non-small cell lung cancer, and melanoma. This post hoc analysis was conducted from March to September 2024. Treatment with atezolizumab. The primary outcome was the association of PD patterns with PPOS. Seven PD patterns were identified based on the enlargement of target and nontarget lesions or new lesions and their combinations. A total of 1377 patients were analyzed across the 5 trials. In RCC, 7 PD patterns significantly affected prognosis. The 6-month PPOS probability ranged from 26% for progression in target and nontarget lesions plus new lesions to 90% for progression in either target or nontarget lesions alone. A modified PD classification was developed that categorized PD into 3 risk levels: low risk (progression of existing lesions), intermediate risk (new lesions without progression of existing lesions), and high risk (progression of existing lesions plus new lesions). This score was associated with PPOS in ICI-treated RCC, with hazard ratios of 0.23 (95% CI, 0.13-0.41; P < .001) and 0.39 (95% CI, 0.23-0.66; P < .001) for low-risk and intermediate-risk PD compared with high-risk PD, respectively. Validation in additional trials confirmed the score's applicability across various tumors. In this study, a survival score was developed based on PD patterns. The risk classification was associated with PPOS across various solid tumors treated with immunotherapy and may therefore enhance prognostication and clinical decision-making, potentially providing a valuable tool for treating patients with PD who are receiving immunotherapy.

Mechanistic Learning for Predicting Survival Outcomes in Head and Neck Squamous Cell Carcinoma.

We employed a mechanistic learning approach, integrating on-treatment tumor kinetics (TK) modeling with various machine learning (ML) models to address the challenge of predicting post-progression survival (PPS)-the duration from the time of documented disease progression to death-and overall survival (OS) in Head and Neck Squamous Cell Carcinoma (HNSCC). We compared the predictive power of model-derived TK parameters versus RECIST and assessed the efficacy of nine TK-OS ML models against conventional survival models. Data from 526 advanced HNSCC patients treated with chemotherapy and cetuximab in the TPExtreme trial were analyzed using a double-exponential model. TK parameters from the first line and maintenance (TKL1) or after four cycles (TK4) were used to predict PPS and post-cycle 4 OS (OS4), combined with 12 baseline parameters. While ML algorithms underperformed compared to the Cox model for PPS, a random survival forest was superior for OS prediction using TK4 and surpassed RECIST-based metrics. This model demonstrated unbiased OS4 prediction, suggesting its potential for improving HNSCC treatment evaluation. Trial Registration: ClinicalTrials.gov identifier: NCT02268695.

A comprehensive analysis of the expression and prognostic significance of signal transducers and activators of transcription family in gastric cancer patients

Abstract Background Understanding the role of the STAT family in gastric cancer (GC) is essential for developing targeted therapies and improving patient outcomes. However, comprehensive analysis of STAT expression and its prognostic significance in GC is limited. This study aims to address this gap by examining STAT expression in normal and GC tissues and evaluating its prognostic value across clinical subgroups. Methods STAT mRNA expression levels were compared between tumor and normal tissues using fold change analysis. Kaplan–Meier curves assessed the correlation between STAT expression and clinical outcomes, with statistical significance determined by the Log-rank test and hazard ratios (HR) with 95% confidence intervals. Subset analyses evaluated STAT expression across GC subtypes and its prognostic value, including in patients with oncogenic mutations. Results Most STAT family members, except STAT4, showed increased expression in GC tissues compared to normal tissues, consistent across various clinical subgroups, suggesting a role in GC pathogenesis. Kaplan–Meier analysis revealed the prognostic significance of STATs in GC. High STAT1 expression was associated with improved overall survival (OS), first progression (FP), and post-progression survival (PPS), indicating a favorable prognosis. In contrast, elevated STAT5A, STAT5B, and STAT6 expression correlated with poor prognosis. Subgroup analysis highlighted the consistent prognostic value of STATs across different histological subtypes, particularly in intestinal-type GC. Additionally, STAT expression had differential prognostic implications based on HER2 status. HER2-positive GC patients with high STAT expression had worse OS and FP rates, while HER2-negative patients with high STAT1 expression had better survival outcomes. Conclusions This study provides valuable insights into STAT expression patterns and their prognostic significance in GC. The upregulation of STATs, except STAT4, suggests their involvement in GC oncogenesis. Notably, high STAT1 expression is a favorable prognostic marker, while increased STAT5A, STAT5B, and STAT6 expression correlates with poor prognosis. These findings underscore the potential of STATs as prognostic markers in GC, guiding personalized treatment strategies and improving patient outcomes.

Transcriptomic Profiling of Carboplatin- and Paclitaxel-Resistant Lung Adenocarcinoma Cells Reveals CSF3 as a Potential Biomarker for the Carboplatin Plus Paclitaxel Doublet Regimens.

This study aimed to generate Car- and Pac-resistant cell lines from the human lung adenocarcinoma H1792 cell line, designated as H1792/Car and H1792/Pac, and perform transcriptome sequencing to identify potential targets. Common differentially expressed genes (Co-DEGs) in both resistant cell lines were identified, followed by hub gene identification. Online validation was conducted through GEPIA and Kaplan-Meier Plotter platforms, with experimental validation performed using real-time quantitative PCR (RT-qPCR). After six months, the H1792/Car and H1792/Pac cell lines exhibited a 10.7-fold and 5.6-fold increase in resistance to Car and Pac, respectively. Flow cytometry analysis demonstrated that both resistant cell lines were resistant to cell cycle arrest and apoptosis induced by Car or Pac. Transcriptomic sequencing identified 123 Co-DEGs, including 72 upregulated and 51 downregulated genes, consistently expressed in both H1792/Car and H1792/Pac cell lines. Among these, 13 hub genes were identified, with colony-stimulating factor 3 (CSF3) uniquely associated with post-progression survival (PPS) in adenocarcinoma patients undergoing chemotherapy. Notably, CSF3 expression was significantly elevated in both H1792/Car and H1792/Pac compared to parental cells. These findings underscore the value of drug-resistant models in uncovering critical biomarkers. CSF3 emerges as a promising guiding marker or potential molecular target for optimizing Car- and Pac-based doublet regimens.

Liver Metastases are Associated with a Short Post-Progression Survival in a Real-World Group of Patients with Melanoma Treated with Checkpoint Inhibitors.

The introduction of immunotherapy (IT) has transformed clinical care of patients with metastatic melanoma. However, many patients still die as a result of progressive disease. Here we analyzed how IT improved survival in a real-world setting. Additionally, we investigated whether IT alters the dynamics and pattern of metastatic progression in different organs resulting from tissue-specific immune microenvironments. We retrospectively compared a group of 61 patients with metastatic melanoma (24 female, 37 male) treated with IT between 2015 and 2018 with a historical control group of 56 patients with metastatic melanoma (21 female, 35 male) treated with chemotherapy between 2005 and 2008 regarding treatment response rates and overall survival as well as the timing and distribution of metastatic progression. Patients with metastatic melanoma treated with IT showed increased response rates and longer overall survival when compared with patients treated with chemotherapy. In addition, treatment with IT altered the dynamics but not the pattern of metastatic progression when compared with treatment with chemotherapy. Interestingly, patients receiving IT lived significantly longer after metastatic progression to lymph nodes, lungs and brain, but not after metastatic progression to the liver. Our results confirm the efficacy of IT in a real-world setting. The altered dynamics of metastases supports studies suggesting a unique role of immune privilege in the liver tissue microenvironment that increases resistance to immunotherapy.

Cost-Effectiveness of Pembrolizumab as First-Line Treatment in Patients with Persistent, Recurrent, or Metastatic Cervical Cancer in the United States.

First-line treatment of persistent, recurrent, or metastatic (advanced) cervical cancer in patients who have a combined positive score (CPS) ≥ 1 with pembrolizumab + chemotherapy versus standard-of-care chemotherapy provides meaningful improvements in overall survival. We conducted a cost-effectiveness analysis from a US payer perspective. A societal perspective scenario was also considered, including productivity gains. The cost-effectiveness of pembrolizumab + chemotherapy versus chemotherapy was assessed using a state-transition model comprising the health states "pre-progression," "post-progression," and "death," with a 1-week cycle length and 50-year time horizon. Patient-level KEYNOTE-826 data informed the efficacy, safety, and health-related quality of life of pembrolizumab + chemotherapy versus chemotherapy at first-line and subsequent treatments. Real-world data were sought to cost subsequent treatments according to US clinical practice. Transition probabilities were derived from parametric survival models fit to time-to-progression, progression-free survival, and post-progression survival patient-level KEYNOTE-826 data. Sensitivity analyses explored the impact on outcomes from variables such as bevacizumab use. According to the state-transition model, pembrolizumab + chemotherapy extended mean life expectancy versus chemotherapy from 1.8 to 6.7 life-years. The mean gain of 4.9 life-years/patient was mostly caused by pembrolizumab delaying progression. Total discounted quality-adjusted life-years (QALY) were 5.0 and 1.3 per patient for pembrolizumab + chemotherapy and chemotherapy, respectively (mean gain: 3.7 QALY/patient). Pembrolizumab + chemotherapy had comparable safety outcomes to chemotherapy alone. Total costs incurred were US $320,247 (pembrolizumab + chemotherapy) versus US $105,446 (chemotherapy; mean incremental costs: US $214,801/patient). The incremental cost-effectiveness ratio of pembrolizumab + chemotherapy versus chemotherapy was US $58,446/QALY. Sensitivity analyses showed results were insensitive to bevacizumab use. Including productivity gains led to an incremental cost-effectiveness ratio of US $58,385 per QALY. Our model-based analysis suggests that first-line treatment of pembrolizumab + chemotherapy in advanced cervical cancer with a CPS ≥ 1 offers a substantial clinical benefit over standard-of-care chemotherapy alone and is cost-effective at a willingness-to-pay threshold of US $150,000. The approximate doubling of life-years and QALYs associated with pembrolizumab + chemotherapy represents a step improvement in the treatment of advanced cervical cancer. ClinicalTrials.gov Identification Number: NCT03635567.

Integrin α6β4 Upregulates PTPRZ1 Through UCHL1-Mediated Hif-1α Nuclear Accumulation to Promote Triple-Negative Breast Cancer Cell Invasive Properties.

Integrin α6β4 drives triple-negative breast cancer (TNBC) aggressiveness through the transcriptional regulation of key genes. Here, we investigated how integrin α6β4 regulates protein tyrosine phosphatase receptor type Z1 (PTPRZ1). Using stable re-expression of integrin β4 (ITGB4) in cells naturally devoid of integrin α6β4 or knockdown or knockout (KO) of ITGB4, we found that integrin α6β4 regulates PTPRZ1 expression. To gain mechanistic insight, we focused on Hif-1α due to the impact of integrin α6β4 on a hypoxia-associated signature. We found that nuclear localization of Hif-1α, but not Hif-2α, was substantially enhanced with integrin α6β4 signaling. Hif-1α knockdown by shRNA or chemical inhibition decreased PTPRZ1 expression, while chemical activation of Hif-1α increased it. Upstream of Hif-1α, integrin α6β4 upregulates UCHL1 to stabilize Hif-1α and ultimately regulate PTPRZ1. Inhibition of UCHL1 and PTPRZ1 dramatically decreases integrin α6β4-mediated cell migration and three-dimensional invasive growth. Finally, public breast cancer database analyses demonstrated that ITGB4 correlates with PTPRZ1 and that high expression of ITGB4, UCHL1, HIF1A, and PTPRZ1 associated with decreased overall survival, distant metastasis free survival, post progression survival, and relapse-free survival. In summary, these findings provide a novel function of integrin α6β4 in promoting tumor invasive phenotypes through UCHL1-Hif-1α-mediated regulation of PTPRZ1.

Importance of driver gene mutation assessment and targeted therapy for patients with early‑stage non‑small cell lung cancer and non‑R0 resection.

Patients with non-small cell lung cancer (NSCLC) and incomplete resection have poor clinical outcomes. The present study aimed to identify risk factors for disease progression and mortality. A total of 65 patients with early-stage NSCLC that underwent operation but had a non-R0 resection between August 2011 and December 2020 were included in the present study, and the clinicopathological features and driver gene mutation status were analyzed. The median follow-up time was 36.2 months; 39 patients (60.0%) experienced disease progression and 3 patients (4.6%) died. In total, 22 patients (33.8%) harbored mutations in driver genes. Multivariate analysis demonstrated that the presence of driver gene mutations was associated with an increased risk of disease progression [adjusted odds ratio, 24.08; 95% confidence interval (CI), 2.77-209.01; P=0.004]. Tumors classed as Eastern Cooperative Oncology Group performance status 2 [adjusted hazard ratio (HR), 3.49; 95% CI, 1.10-11.03; P=0.033], stage II-IIIB tumors (adjusted HR, 2.55; 95% CI, 1.06-6.17; P=0.037) and the presence of a driver gene mutation (adjusted HR, 3.28; 95% CI, 1.55-6.94; P=0.002) were associated with a significantly reduced progression-free survival (PFS). Driver gene-targeted therapy was associated with an increased post-progression survival for patients that were reported to have disease progression (adjusted HR, 0.38; 95% CI, 0.16-0.91; P=0.030). There was no significant impact of driver gene mutation status on the overall survival (OS) of patients. Although the presence of a driver gene mutation was associated with an increased risk of disease progression and a reduced PFS, it was demonstrated that patients with disease progression may benefit from driver gene-targeted therapy, as patients with driver gene-targeted therapy had a similar OS compared with that of patients with a driver gene-negative or unknown status. Therefore, early comprehensive analysis of driver gene mutation status may be recommended for early-stage NSCLC cancer patients experiencing non-R0 resection.

Progression-free survival versus post-progression survival and overall survival in WHO grade 2 gliomas.

Progression-free survival (PFS) remains to be validated as an outcome measure for diffuse WHO grade 2 gliomas, and knowledge about the relationships between PFS, post-progression survival (PPS), and overall survival (OS) in this subset of tumors is limited. We sought to assess correlations between PFS and OS, and identify factors associated with PFS, PPS, and OS in patients treated for diffuse supratentorial WHO grade 2 gliomas. We included 319 patients from three independent observational cohorts. The correlation between PFS and OS was analyzed using independent exponential distributions for PFS and time from progression to death. Cox proportional hazards models were used to determine the effects of covariates on PFS, PPS, and OS. The overall correlation between PFS and OS was rs0.31. The correlation was rs 0.37 for astrocytomas and rs 0.19 for oligodendrogliomas. Longer PFS did not predict longer PPS. Patients with astrocytomas had shorter PFS, PPS, and OS. Larger preoperative tumor volume was a risk factor for shorter PFS, while older age was a risk factor for shorter PPS and OS. Patients who received early radio- and chemotherapy had longer PFS, but shorter PPS and OS. We found a weak correlation between PFS and OS in WHO grade 2 gliomas, with the weakest correlation observed in oligodendrogliomas. Our analyses did not demonstrate any association between PFS and PPS. Critically, predictors of PFS are not necessarily predictors of OS. There is a need for validation of PFS as an endpoint in diffuse WHO grade 2 gliomas.

Evaluation of the prognostic value of the new 9th edition Tumor-Node-Metastases (TNM) staging system for epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma patients with bone metastases

BackgroundThere are some changes in the new 9th edition Tumor-Node-Metastases (TNM) staging system for lung cancer, including subdividing M1c into M1c1 and M1c2 stage. The aim of this study was to assess the prognostic performance of the updated classification system and try to provide some real-world application data among advanced lung adenocarcinoma patients with bone metastases.MethodsAdvanced lung adenocarcinoma patients in M1c stage with bone metastases who receiving first-line first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and T790M-guided osimertinib as the second-line therapy were retrospectively screened from December 2016 to December 2021. A total of 126 patients were enrolled in this study. 62 patients and 64 patients were subdivided into M1c1 and M1c2 groups according to the 9th edition of TNM staging system.The first-line real-world progression-free survival (1LrwPFS), the second-line real-world progression-free survival (2LrwPFS), post-progression survival (PPS) and real-world overall survival (rwOS) were analyzed.ResultsThe overall median rwOS was 40.1 months (95% CI 35.996–44.204). 1LrwPFS was 13.9 months (95% CI 12.653–15.147) and 2LrwPFS was 14.5 months (95% CI 11.665–17.335) for all patients.Patients in M1c2 stage was inferior to M1c1 stage patients in rwOS (35.2 months vs. 42.9 months, HR = 0.512, P = 0.005). 2LrwPFS was moderately correlated with rwOS (r = 0.621, R2 = 0.568, P = 0.000). Multivariate analysis showed performance status (PS) score ≥ 2 and TP53 alteration positive were independent prognostic factors of worse rwOS.ConclusionsMore refined stratification of M1c according to the 9th edition of TNM staging system is conducive to the judgment of prognosis and the implementation of precision medicine for patients.

Second-line treatment patterns and outcomes in advanced HCC after progression on atezolizumab/bevacizumab

Second-line treatment patterns and outcomes in advanced HCC after progression on atezolizumab/bevacizumab