Comparable Survival Research Articles

Which is the best TACE agent for patients with different NLR hepatocellular carcinomas? A systematic review and network meta-analysis

BackgroundTransarterial chemoembolization (TACE) is a common treatment for hepatocellular carcinoma (HCC), but the best therapeutic agent for TACE treatment has not been determined. The neutrophil/lymphocyte ratio (NLR) is a systemic immune system marker; however, the ability of the NLR to predict the prognosis of patients with HCC is unknown, and no studies have been conducted to determine the most appropriate TACE regimen for HCC patients with different NLRs. MethodsThe PubMed, Embase, Web of Science, and CNKI databases were searched through May 28, 2023. Comparisons of overall survival (OS) among cohort studies with different NLRs and different TACE treatment regimens were performed with a random effects model. FindingsThirty-five studies involving 9210 patients were included in this meta-analysis. The results showed that Group 3–4 (NLR<2.5) patients had a significantly longer OS than Group 1–2 (NLR 2.5–5.0). Among the patients, Group 1–3 (NLR 2.0–5.0) patients had the best survival after treatment with adriamycin (lnHR (95 % CI = 0.48 [0.31, 0.75] and lnHR (95 % CI = 0.41 [0.19, 0.91]). Among the Group 4 patients (NLR<2.0), the best outcome was obtained with platinum + adriamycin (lnHR (95 % CI = 0.59 [0.45, 0.78]), followed by adriamycin. A subgroup analysis of TACE combined with other treatments showed that adriamycin combined with sorafenib was the most effective and superior to the other treatment agents. InterpretationThe NLR can be used to predict the prognosis of HCC patients treated with TACE; the higher the NLR is, the worse the prognosis. Adriamycin may be the best therapeutic agent for HCC patients treated with TACE.

Clinicopathologic and molecular correlates to neoadjuvant chemotherapy-induced pathologic response in breast angiosarcoma.

Both primary and secondary breast angiosarcoma (AS) are characterized by multifocal presentation and aggressive behavior. Despite multimodality therapy, local and distant relapse rates remain high. Therefore, neoadjuvant chemotherapy (NACT) is employed to improve the R0 resection rates and survival, but its benefits remain controversial. Herein, we investigate pathologic and molecular correlates to NACT-induced histologic response in a group of 29 breast AS, 4 primary and 25 radiation-associated (RA). The two NACT regimens applied were anthracycline- and non-anthracycline-based. The pathologic response grade was defined as: I: ≤ 50%, II: 51%-90%, III: 91%-99%, and IV: 100%. An additional 45 primary AS and 102 RA-AS treated by surgery alone were included for survival comparison. The genomic landscape was analyzed in a subset of cases and compared to a cohort of AS without NACT on a paired tumor-normal targeted DNA NGS platform. All patients were females, with a median age of 31 years in primary AS and 68 years in RA-AS. All surgical margins were negative in NACT group. The NACT response was evenly divided between poor (Grades I-II; n = 15) and good responders (Grades III-IV; n = 14). Mitotic count >10/mm2 was the only factor inversely associated with pathologic response. By targeted NGS, all 10 post-NACT RA-AS demonstrated MYC amplification, while both primary AS harbored KDR mutations. TMB or other genomic alterations did not correlate with pathologic response. All four patients with Grade IV response remained free of disease. The good responders had a significantly better disease-specific survival (p = 0.04). There was no survival difference with NACT status or the NACT regimens applied. However, NACT patients with MYC-amplified tumors showed better disease-free survival (p = 0.04) compared to MYC-amplified patients without NACT. The overall survival of NACT group correlated with size >10 cm (p = 0.02), pathologic response (p = 0.04), and multifocality (p = 0.01) by univariate, while only size >10 cm (p = 0.03) remained significant by multivariate analysis.

Abstract CT274: BGB-A317-LBL-007-202: A phase 2, randomized, active-controlled, open-label study to evaluate the efficacy and safety of LBL-007 (anti-LAG-3) in combination with tislelizumab (TIS; anti-PD-1) plus chemotherapy (chemo) as first-line (1L) treatment in patients with unresectable locally advanced/metastatic esophageal squamous cell carcinoma (ESCC)

Abstract Background: ESCC is the predominant histological subtype of esophageal cancer, accounting for 85% of cases. Patients (pts) with locally advanced/metastatic ESCC have poor clinical outcomes, with a 5-year survival rate of 6.1% for pts with distant metastases. 1L treatment with programmed cell death protein-1 (PD-1) inhibitors + platinum-based chemo has become the new standard of care for metastatic ESCC, however, there is an unmet need for enhanced treatment efficacy and a prolonged life span. LBL-007 is a monoclonal antibody (mAb) against lymphocyte activation gene-3 (LAG-3), an immune checkpoint receptor that negatively regulates T-cell activity. TIS is an anti-PD-1 mAb that blocks the PD-1/programmed death-ligand 1 (PD-L1) immune checkpoint, resulting in T-cell activation. This study (NCT06010303) aims to evaluate the efficacy and safety of LBL-007 + TIS + chemo as a 1L treatment in pts with unresectable, locally advanced/metastatic ESCC. Methods: This phase 2 study will enroll approximately 116 pts with a pathologically confirmed diagnosis of unresectable, locally advanced/metastatic ESCC and no prior systemic therapy. Pts will be randomized 2:1 to either Arm A (LBL-007 600 mg intravenously [IV] every 3 weeks [Q3W] + TIS 200 mg IV Q3W + chemo doublet) or Arm B (TIS 200 mg IV Q3W + chemo doublet), stratified by PD-L1 expression (tumor area positivity score ≥10% or &amp;lt;10%). The chemo doublet will consist of either cisplatin (60-80 mg/m2 IV Q3W) + 5-fluorouracil (750-800 mg/m2 IV daily on Days 1-5 Q3W), or cisplatin + paclitaxel (175 mg/m2 IV Q3W), determined by the investigator before randomization. Treatments will be administered until disease progression, intolerable toxicity, or withdrawal for other reasons. The primary endpoint is the overall response rate, as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints include progression-free survival, duration of response, and disease control rate (all by investigator per RECIST v1.1), and the incidence and severity of adverse events per National Cancer Institute-Common Terminology Criteria for Adverse Events v5.0. A safety monitoring committee is monitoring the safety of LBL-007 + TIS + chemo vs TIS + chemo. Exploratory endpoints include comparison of overall survival, assessment of predictive, prognostic, and pharmacodynamic biomarkers, pharmacokinetic evaluation of LBL-007 and TIS, and immunogenicity. The study is currently recruiting at approximately 46 sites across Asia, including Taiwan, mainland China, South Korea, and Thailand. Citation Format: Sook Ryun Park, Ming-Huang Chen, Arunee Dechaphunkul, Ningning Ding, Xiao Lin, Jinghui Zhang, Vivian Li, Qiao Li, Yi Ba. BGB-A317-LBL-007-202: A phase 2, randomized, active-controlled, open-label study to evaluate the efficacy and safety of LBL-007 (anti-LAG-3) in combination with tislelizumab (TIS; anti-PD-1) plus chemotherapy (chemo) as first-line (1L) treatment in patients with unresectable locally advanced/metastatic esophageal squamous cell carcinoma (ESCC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT274.

Comparison of 1-year survival between patients initiating chronic hemodialysis under public and private health insurance: register-based data analysis from Brazil.

Brazil has one of the world's highest numbers of patients on hemodialysis (HD). Most dialysis centers are private and perform HD for patients with private and public health insurance. We compared 1-year survival between patients initiating chronic HD with public and private health insurance. This is an HD register-based retrospective cohort. Adult patients starting HD from January 2011 to December 2021 were included. Survival analysis was stratified according to the period entered in the HD register. Multivariate Cox regression focused on 1-year survival differences between private and public patients. In the final sample (n = 5114), 68.5% of participants had public and 31.3% to private health insurance, with overall 1-year survival of 92.8% and 89.9%, respectively (p = 0.002). Crude analysis showed a slightly higher survival rate among patients with public health insurance than those with private health insurance (91 vs. 87%, p = 0.030) in the first period (2019-21). However, the adjusted hazard ratio (HR) did not remain significantly higher for patients with private health insurance compared to those with public health insurance (HR = 1.07; 95% CI 0.80-1.41; p = 0.651), even after propensity score matching of the groups by several baseline features. Brazilian chronic HD patients funded by either private health plans or the public system have a similar 1-year mortality risk after controlling for several sociodemographic and clinical parameters.

Outcome differences by sex in oncology clinical trials

Identifying sex differences in outcomes and toxicity between males and females in oncology clinical trials is important and has also been mandated by National Institutes of Health policies. Here we analyze the Trialtrove database, finding that, strikingly, only 472/89,221 oncology clinical trials (0.5%) had curated post-treatment sex comparisons. Among 288 trials with comparisons of survival, outcome, or response, 16% report males having statistically significant better survival outcome or response, while 42% reported significantly better survival outcome or response for females. The strongest differences are in trials of EGFR inhibitors in lung cancer and rituximab in non-Hodgkin’s lymphoma (both favoring females). Among 44 trials with side effect comparisons, more trials report significantly lesser side effects in males (N = 22) than in females (N = 13). Thus, while statistical comparisons between sexes in oncology trials are rarely reported, important differences in outcome and toxicity exist. These considerable outcome and toxicity differences highlight the need for reporting sex differences more thoroughly going forward.

Abstract 2490: Quantification of tumor fraction and outcomes association in a real-world non-small cell lung cancer (NSCLC) cohort using a tissue agnostic epigenomic circulating tumor DNA (ctDNA) assay

Abstract Background: The validity of ctDNA assays for evaluating molecular response to therapy by measuring changes in variant allele fraction (VAF) while on treatment is well established, but they are prone to limitations such as low ctDNA levels and interference from copy number variation and clonal hematopoeisis (CH), which may be overcome by methylation-based quantification. ctDNA levels may be monitored throughout a patient's (pts) journey to indicate when relapse or progression is present, often sooner than current methods (RECIST). Here we describe the performance of a methylation-based ctDNA assay to quantify ctDNA levels and correlate changes with outcomes in a real-world NSCLC cohort. Methods: RADIOHEAD is a pan-tumor observational study of 1200 patients on standard of care ICI treatment regimens with plasma samples collected prospectively for retrospective analysis. We randomly selected 241 NSCLC pts that have a combined total of 761 samples (236 baseline, 191 C3D1, and 128 at 6 months post first dose). Samples were analyzed using a commercial NGS assay, which quantifies circulating tumor fraction (cTF) via interrogating thousands of methylation sites from ctDNA, validated with LoB, LoD, LoQ, and linearity studies. Cox proportional hazards (CPH) were used for comparison of real-world progression free survival (rwPFS). Gender, age, disease stage, and blood-assessed tumor mutational burden (bTMB) were included as covariates. Median rwPFS was calculated using Kaplan Meier analysis. rwPFS ordinal groups were defined as PFS event within 3mo, 3-6mo, 6-12mo, and greater than 12mo, and association with early ctDNA changes was assessed with a chi-squared test. Results: In this cohort, 4, 11, 83 and 142 pts were stage I to IV, respectively (1 unknown). Methylation based detection of ctDNA at baseline or C3D1 was associated with shorter rwPFS (baseline: mPFS 12.7 mo [9.3-19.5] vs NR [16.4-NR]; HR=2.2 [1.3-3.7] p&amp;lt;0.005, C3D1: mPFS 12.4 mo [9.3-16.1] vs NR [19.5-NR] HR= 2.2 [1.3-3.5], p&amp;lt;0.005) independent of stage, gender, or age. Longer rwPFS was associated with &amp;gt;95% reduction in cTF from baseline to C3D1 or low ctDNA at both timepoints (rwPFS &amp;lt;3mo = 12.5%, 3-6 mo = 30.8%, 6-12 = 37.1%, ≥12 mo = 55.3%; N=153, p=0.015). For pts with ctDNA not detected at C3D1, ctDNA detection at 6 months post first dose was strongly associated with shorter rwPFS (mPFS 13.5 mo [9.5-NR] vs. NR [19.5-NR]; HR= 6.2 [1.9-20.1], p&amp;lt;0.005). Conclusions: These data demonstrate a significant association of ctDNA detection via methylation-based cTF and on-treatment changes in cTF with rwPFS. Furthermore, subsequent cTF detection 6-months on-treatment, without cTF detected early on-treatment was associated with worse outcomes, suggesting the value of serial monitoring to improve identification of patients likely to progress. Citation Format: Sara Wienke, Sean Gordon, Samantha Liang, Jing Wang, Reagan Barnett, Kyle Chang, Shile Zhang, Carin R. Espenschied, Katie Quinn, Kimberly Banks. Quantification of tumor fraction and outcomes association in a real-world non-small cell lung cancer (NSCLC) cohort using a tissue agnostic epigenomic circulating tumor DNA (ctDNA) assay [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2490.

Adjusted Indirect Treatment Comparison of Progression-Free Survival with D-Rd and VRd Based on MAIA and SWOG S0777 Individual Patient-Level Data.

Daratumumab plus lenalidomide and dexamethasone (D-Rd) and bortezomib plus lenalidomide and dexamethasone (VRd) are commonly used treatment combinations for transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). D-Rd and VRd demonstrated superior efficacy relative to lenalidomide and dexamethasone (Rd) in the MAIA and SWOG S0777 trials, respectively, but have not been compared directly in a head-to-head trial. Naïve comparisons of efficacy across the two trials may be biased because MAIA enrolled only TIE patients (median age 73years), whereas SWOG S0777 enrolled both TIE patients and transplant-eligible patients who chose to defer/refuse frontline stem cell transplantation (median age 63years). The present study compared progression-free survival (PFS) in TIE patients with NDMM treated with D-Rd versus VRd based on an adjusted indirect treatment comparison (ITC) that leveraged individual patient-level data from MAIA and SWOG S0777. Harmonized inclusion/exclusion criteria (including age ≥ 65years as a proxy for transplant ineligibility) and propensity-score weighting were used to balance the trial populations on measured baseline characteristics. After differences in trial populations were adjusted for, an anchored ITC was performed wherein within-trial PFS hazard ratios (HRs) for D-Rd versus Rd and VRd versus Rd were estimated and used to make indirect inference about PFS for D-Rd versus VRd. PFS HRs were 0.52 (95% confidence interval [CI] 0.41-0.67) for D-Rd versus Rd based on MAIA data, 0.88 (95%CI 0.63-1.23) for VRd versus Rd based on SWOG S0777 data, and 0.59 (95%CI 0.39-0.90) for the Rd-anchored ITC of D-Rd versus VRd. Sensitivity and subgroup analyses produced results consistent with the primary results. This anchored ITC demonstrated a greater PFS benefit for D-Rd versus VRd in TIE patients with NDMM. In the absence of head-to-head trials comparing D-Rd and VRd, the present trial may help inform treatment selection in this patient population.

Left Internal Thoracic Artery versus Saphenous Vein Grafts to Left Anterior Descending Artery after Isolated Coronary Artery Bypass Surgery.

This study compared perioperative outcomes and long-term survival of saphenous vein grafts (SVGs) versus left internal thoracic artery (LITA) to left anterior descending artery (LAD) in isolated coronary artery bypass graft surgery (CABG). In this retrospective, single-centre study, we included patients with primary isolated CABG from January 2001 to July 2022. Baseline demographics were compared between SVG-LAD and LITA-LAD. Univariable and multivariable regressions were performed for predictors of in-hospital death. Propensity score matching was performed for LITA-LAD vs. SVG-LAD. Kaplan-Meier survival curves were generated for comparison of survival. Cox proportional hazards model was used for predictors of survival. A total of 8237 patients (1602 SVG-LAD/6725 LITA-LAD) were included. Median age was 67.9 years (LITA-LAD; 67.1 years vs. SVG-LAD; 71.7 years, p < 0.01). A total of 1270 pairs of SVG-LAD were propensity-matched to LITA-LAD. In matched cohorts, in-hospital mortality (0.8% vs. 1.6%, LITA-LAD and SVG-LAD respectively; p = 0.07), deep sternal wound infection, new cerebrovascular events, renal replacement therapy and hospital stay >30 days were similar. SVG-LAD did not adversely affect in-hospital mortality (OR; 2.03, CI; 0.91, 4.54, p = 0.08). Median long-term survival was similar between the groups (13.7 years vs. 13.1 years for LITA-LAD and SVG-LAD respectively, log rank p < 0.31). SVG-LAD was not a predictor of adverse long-term survival. (HR; 1.06, 95% CI; 0.92, 1.22, p < 0.40). Long-term survival was better with LITA-LAD for LVEF <30% (log rank p < 0.03). There was no difference in the propensity-matched cohorts for use of SVG vs. LITA to the LAD. Further contemporary long-term studies are needed for substantiation.

Extent of Surgery and Survival of Osteosarcoma: A Retrospective Population-Based Study.

Background Osteosarcoma (OSC) is the most common primary bone tumor and is often managed surgically. Few prior investigations have assessed differences in OSC survival by specific surgical techniques at a national registry level. We sought to compare survival based on surgical subtypes for OSC patients in the Surveillance, Epidemiology, and End Results (SEER) database. Methodology We searched the SEER database for malignant OSCs diagnosed between 2000 and 2019 which were surgically managed. Separate survival comparisons were made for one and five years for wide excision (local tumor destruction or resection versus partial resection) and radical excision (radical resection with limb-sparing versus limb amputation with or without girdle resection). Results A total of 4,303 patients were included, of whom 3,587 were surgically managed. There were no survival differences between local destruction and partial resection (hazard ratio = 0.826, p = 0.303). However, younger age, lower staging, and management without radiation were associated with improved survival. The radical excision comparison showed limb amputation was associated with worse survival than limb-sparing surgery (hazard ratio = 1.531, p < 0.001). Younger age, female sex, lower stage, receipt of chemotherapy, and neoadjuvant plus adjuvant chemotherapy were associated with improved survival while Black and American Indian or Alaska Native were associated with worse survival. Conclusions Our findings show that patients managed with limb-sparing radical resection survived significantly compared to limb amputation. There were no differences in survival for wide excision surgeries. The use of a combination of neoadjuvant and adjuvant chemotherapy also yields improved survival. OSC survival may be optimized with limb-sparing surgery with a combination of neoadjuvant and adjuvant chemotherapy.

Thirty-day mortality after palliative radiotherapy in advanced cancer patients: Optimizing end-of-life care in Asia.

Evidence-based guidelines recommend hypofractionated palliative radiotherapy (PRT); nonetheless, many patients receive prolonged course of PRT. To identify patients with limited benefits from PRT in end-of-life care, we evaluated the pattern of PRT at an Asian institution and factors associated with 30-day mortality after PRT (30dM). We retrospectively reviewed 228 patients who died after PRT in Yonsei Wonju Severance Christian hospital between October 2014 and March 2022. The associations between clinical factors and survival were assessed using the Cox proportional hazards method. Survival was analysed using the existing models to evaluate their performance in our cohort. The median PRT duration was 13 (IQR, 7-15) days. Only 11.4% of the patients were treated with hypofractionated radiotherapy. One-third of the patients (32.9%) could not complete PRT and 39 (17.1%) died during PRT. The 30dM was 31.6%. The median time from PRT to death was 17 (IQR, 11-23) days for the patients who died within 30 days. The number of involved organs (≤2 vs. >2; P < 0.001), albumin level (<3.3 vs. ≥3.3; P = 0.016), admission during PRT (P < 0.001), admission 3 months before PRT (P = 0.036) and ICU care during PRT (P < 0.001) were prognostic factors. A comparison of survival based on the existing models yielded unsatisfactory results in our cohort. Almost one-third of the patients received PRT in the last 30 days of life. The use of hypofractionation for PRT was low in this Asian population. Further research is necessary to develop a predictive model of early mortality, allowing tailored end-of-life care for Asian patients.

Non-liver-related mortality in the DAA era: Insights from post-SVR patients with and without previous HCC history.

Mortality after sustained virological response (SVR) with interferon-free direct-acting antiviral (IFN-free DAA) therapy is crucial for optimizing post-SVR patient care, but it remains unclear, especially regarding non-liver-related mortality. Consecutive post-SVR patients from 14 institutions were stratified into three cohorts: A (without advanced fibrosis and without prior HCC), B (with advanced fibrosis and without prior HCC), and C (curative HCC treatment). We assessed mortality (per 1000 person-years [/1000PY]) post-SVR. Mortality rates were compared between cohorts A and B and the general population using age- and sex-adjusted standardized mortality ratio (SMR). Comparison of survival between each cohort was performed using propensity-score (PS) matching with sex, age, and comorbidity. In cohort A (n = 762; median age, 65 years), 22 patients died (median follow-up, 36 months); all-cause mortality was 10.0/1000PY, with 86.4% non-liver-related deaths. In cohort B (n = 519; median age, 73 years), 27 patients died (median follow-up, 39 months); all-cause mortality was 16.7/1000PY, with 88.9% non-liver-related deaths. In both cohorts, malignant neoplasm was the most common cause of death; all-cause mortality was comparable to that of the general population (SMR: 0.96 and 0.92). In cohort C (n = 108; median age, 75 years), 15 patients died (median follow-up, 51 months); all-cause mortality was 36.0/1000PY, with 53.3% liver-related deaths. PS matching showed no significant survival differences between cohorts A and B, both of which had better survival than cohort C. Mortality varies based on HCC history in the DAA era; nevertheless, attention should be paid to non-liver-related deaths in all post-SVR patients.

Comparison of clinical outcomes of several risk stratification tools in newly diagnosed AML patients: A real-world evidence in our current therapeutic era.

AML classification tools have been developed to stratify the risk at AML diagnosis. There is a need to evaluate these tools in the current therapeutic era. In this retrospective study, we compared five classifiers: ELN 2017, ELN 2022, ALFA classifier, Papaemmanuil etal. classifier, and Lindsley etal. classifier, in a real-life cohort of 281 patients newly diagnosed for AML in Nice University Hospital. In our cohort median age was 68 years old, sex ratio was M/F 56%/44%, performance status was lower than 2 in 73.1% of patients, AML subtype was "De novo" in 71.5%, "secondary" in 22.4%, and "therapy-related" in 6.0% of patients. Intensive chemotherapy was used in 53.0% of patients, and non-intensive chemotherapy in 40.6% of patients. Molecular analysis was available in a large majority of patients and the main mutations found were NPM1 (22.7%), DNMT3A (17.4%), TP53 (13.1%), TET2 (12.4%), and FLT3-ITD (12.4%). In our findings, the comparison of overall survival between the three prognostic groups in the global cohort was statistically significant in all classifiers: ELN 2017 p < 0.0001, ELN 2022 p < 0.0001, ALFA classifier p < 0.0001, Papaemmanuil classifier p < 0.0001, Lindsley classifier p = 0.001. ELN 2017, ELN 2022, ALFA classifier, Papaemmanuil classifier, and Lindsley classifier were calculated respectively in 99%, 99%, 89%, 90%, and 89% of patients. Using Akaike's information criteria (AIC) to compare all five classifiers, ELN 2022 is the best classifier into younger and older patients and for prognosis.

The efficacy and safety of adding anlotinib in gradual progression on third-generation EGFR-TKIs for EGFR-mutant advanced nonsmall cell lung cancer.

Acquired resistance is unavoidable with the approval of third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for first-line therapy of advanced non small cell lung cancer (NSCLC). Some studies have found that combining antiangiogenesis medicines with EGFR-TKI may benefit clinical outcomes in EGFR-mutant NSCLC. However, it is unclear whether EGFR-TKI paired with antiangiogenesis therapy could further improve survival for patients with gradual progression. Thus, we comprised the clinical effectiveness and safety of continuous EGFR-TKI in combination with anlotinib and EGFR-TKI alone in patients who had gradual progression on third-generation EGFR-TKI treatment. The comparison of progression-free survival (PFS) and overall survival(OS) between two groups used the Kaplan-Meier method. Our study comprised 121 eligible patients in total. The objective response rates were 25.0% and 0%, and the disease response rate was 91.7% and 86.9% in the combination group and EGFR-TKIs monotherapy group. The median PFS of combined anlotinib and EGFR-TKI treatment was 6.7 months and the median PFS was 3.6 months in the EGFR-TKI monotherapy group ( P < 0.001). There were no significant differences between the two groups in OS. The common adverse reactions were diarrhea (21.7%), hypertension (21.6%) and proteinuria (20.0%) in the combination group. Seven patients experienced a grade 3 or higher adverse event, no patients discounted the treatment or died due to the toxicity. Our study indicated that, when combined with anlotinib following gradual progression on EGFR-TKIs, it was more efficacious for EGFR-mutant NSCLC patients than EGFR-TKI monotherapy. And the toxicity was clinically manageable.

Comparison of postoperative survival between early-onset and late-onset adenocarcinoma of esophagogastric junction: a population-based study.

The prognosis of early-onset adenocarcinoma of esophagogastric junction (AEG) remains unclear. This research aimed at comparing the prognosis between early-onset and late-onset AEGs. We extracted eligible patients with surgically resected, pathologically confirmed, nonmetastatic AEG from the Surveillance, Epidemiology, and End Results database from 2004 to 2015. The cutoff age of early-onset AEG was set at ≤50years old. Univariate and multivariate Cox analysis as well as competing risk model were adopted for comparing overall survival (OS) and cancer-specific survival (CSS) between early-onset and late-onset AEGs. In addition, multiple imputation and propensity score matching (PSM) were also carried out for sensitivity analysis. In total, 4610 eligible AEG patients were collected in this study, including 610 early-onset AEGs and 4000 late-onset AEGs. Kaplan-Meier curves revealed significantly better survival in early-onset AEGs than late-onset AEGs. After interpolating missing data by multiple imputation, multivariate Cox regression analysis similarly showed better OS and CSS in early-onset AEGs. By using PSM analysis at a ratio of 1:1, we matched 610 early-onset AEG patients with 610 late-onset AEG patients. After PSM, univariate Cox regression model still revealed favorable prognosis in early-onset AEGs. Similar results were confirmed by performing PSM analysis at a ratio of 1:2 and 1:3. In addition, competing risk model demonstrated significantly lower cancer-specific death in early-onset AEGs compared to late-onset AEGs before and after matching. By applying several effective sensitivity analyses, we reported significantly favorable OS and CSS in early-onset AEGs compared to late-onset AEGs.

Equivalent uniform RBE-weighted dose in eye plaque brachytherapy.

Brachytherapy for ocular melanoma is based on the application of eye plaques with different spatial dose nonuniformity, time-dependent dose rates and relative biological effectiveness (RBE). We propose a parameter called the equivalent uniform RBE-weighted dose (EUDRBE) that can be used for quantitative characterization of integrated cell survival in radiotherapy modalities with the variable RBE, dose nonuniformity and dose rate. The EUDRBE is applied to brachytherapy with 125I eye plaques designed by the Collaborative Ocular Melanoma Study (COMS). The EUDRBE is defined as the uniform dose distribution with RBE=1 that causes equal cell survival for a given nonuniform dose distribution with the variable RBE>1. The EUDRBE can be used for comparison of cell survival for nonuniform dose distributions with different RBE, because they are compared to the reference dose with RBE=1. The EUDRBE is applied to brachytherapy with 125I COMS eye plaques that are characterized by a steep dose gradient in tumor base-apex direction, protracted irradiation during time intervals of 3-8 days, and variable dose-rate dependent RBE with a maximum of about 1.4. The simulations are based on dose of 85Gy prescribed to the farthest intraocular extent of the tumor (tumor apex). To compute the EUDRBE in eye plaque brachytherapy and correct for protracted irradiation, the distributions of physical dose have been converted to non-uniform distributions of biologically effective dose (BED) to include the biological effects of sublethal cellular repair, Our radiobiological analysis considers the combined effects of different time-dependent dose rates, spatial dose non-uniformity, dose fractionation and different RBE and can be used to derive optimized dose regimens brachytherapy. Our simulations show that the EUDRBE increases with the prescription depths and the maximum increase may achieve 6% for the tumor height of 12mm. This effect stems from a steep dose gradient within the tumor that increases with the prescription depth. The simulations also show that the EUDRBE increase may achieve 12% with increasing the dose rate when implant duration decreases. The combined effect of dose nonuniformity and dose rate may change the EUDRBE up to 18% for the same dose prescription of 85Gy to tumor apex. The absolute dose range of 48-61Gy (RBE) for the EUDRBE computed using 4 or 5 fractions is comparable to the dose prescriptions used in stereotactic body radiation therapy (SBRT) with megavoltage X-rays (RBE=1) for different cancers. The tumor control probabilities in SBRT and eye plaque brachytherapy are very similar at the level of 80% or higher that support the hypothesis that the selected approximations for the EUDRBE are valid. The computed range of the EUDRBE in 125I COMS eye plaque brachytherapy suggests that the selected models and hypotheses are acceptable. The EUDRBE can be useful for analysis of treatment outcomes and comparison of different dose regimens in eye plaque brachytherapy.

Disparities in treatment modalities and survival among older patients with high-grade serous ovarian cancer

BackgroundUndertreatment of ovarian cancer is common among older women. We aimed to evaluate the treatment modalities offered to older patients and their impact on overall survival (OS).MethodsThe study identified 5,055 patients with high-grade serous ovarian cancer and 3584 patients with advanced stage (IIIC + IV) disease from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010, to December 31, 2017. We performed comparisons of OS and ovarian cancer-specific survival (OCSS) across age groups using a Cox proportional hazards model.ResultsVery elderly patients (≥ 75 years old) received treatment with significantly less surgical complexity, such as no lymphadenectomy (59.7% vs. 48.6%; p < 0.001) and a lower rate of optimal debulking surgery (44.0% vs. 52.7%; p < 0.001), as well as lower rates of chemotherapy (78.2% vs. 89.4%; P<0.001) and standard treatment (70.6% vs. 85%; p < 0.001). High proportions of both very elderly and elderly patients received neoadjuvant chemotherapy (NACT), with no significant difference (38.7% vs. 36.2%; P = 0.212). Patients aged ≥ 75 years had significantly worse OS and OCSS.ConclusionWith increasing age, the survival rate of women with ovarian cancer decreases significantly. Noticeably fewer ovarian cancer patients aged over 75 years receive standard treatments, and more very elderly patients are treated with NACT.

Clinical value of the expression levels of tumor protein D52 and miR-133a on prognosis assessment of pancreatic cancer surgery.

To investigate the clinical value of the expression levels of tumor protein D52 (TPD52) and miR-133a on the prognosis assessment of pancreatic cancer surgery. This was a retrospective study. Ninety-seven patients who underwent radical surgery for pancreatic cancer in Cangzhou Central Hospital from January 2018 to January 2022 were selected and divided into four groups: TPD52 high expression group, TPD52 low expression group, miR-133a high expression group and miR-133a low expression group. The relationship between the expression levels of TPD52 and miR-133a and the clinicopathological features of patients with pancreatic cancer was analyzed. The COX regression model was used to analyze the risk factors affecting the prognosis of patients with pancreatic cancer. The high expression rate of TPD52 and the low expression rate of miR-133a in pancreatic cancer tissues were higher than those in normal paracancerous tissues(P<0.05). Based on the comparison of prognosis and survival, the median survival time of patients with high expression of TPD52 and low expression of miR-133a was lower than that of patients with low expression of TPD52 and high expression of miR-133a, with a statistically significant difference(P<0.05). Moreover, multivariate Cox regression analysis showed that low differentiation of pancreatic cancer, III-IV stage of TNM, high expression of TPD52, as well as low expression of miR-133a were independent risk factors for postoperative survival of patients with pancreatic cancer(P<0.05). TPD52 is expressed at a high level whereas miR-133a at a low level in pancreatic cancer tissues, both of which together with low differentiation of pancreatic cancer and III-IV stage of TNM constitute independent risk factors affecting the surgical prognosis of patients with pancreatic cancer.

Cancer Precision-Prevention trial of Metformin in adults with Li Fraumeni syndrome (MILI) undergoing yearly MRI surveillance: a randomised controlled trial protocol

BackgroundLi-Fraumeni syndrome (LFS) is a rare autosomal dominant disease caused by inherited or de novo germline pathogenic variants in TP53. Individuals with LFS have a 70–100% lifetime risk of developing cancer. The current standard of care involves annual surveillance with whole-body and brain MRI (WB-MRI) and clinical review; however, there are no chemoprevention agents licensed for individuals with LFS. Preclinical studies in LFS murine models show that the anti-diabetic drug metformin is chemopreventive and, in a pilot intervention trial, short-term use of metformin was well-tolerated in adults with LFS. However, metformin’s mechanism of anticancer activity in this context is unclear.MethodsMetformin in adults with Li-Fraumeni syndrome (MILI) is a Precision-Prevention phase II open-labelled unblinded randomised clinical trial in which 224 adults aged ≥ 16 years with LFS are randomised 1:1 to oral metformin (up to 2 mg daily) plus annual MRI surveillance or annual MRI surveillance alone for up to 5 years. The primary endpoint is to compare cumulative cancer-free survival up to 5 years (60 months) from randomisation between the intervention (metformin) and control (no metformin) arms. Secondary endpoints include a comparison of cumulative tumour-free survival at 5 years, overall survival at 5 years and clinical characteristics of emerging cancers between trial arms. Safety, toxicity and acceptability of metformin; impact of metformin on quality of life; and impact of baseline lifestyle risk factors on cancer incidence will be assessed. Exploratory end-points will evaluate the mechanism of action of metformin as a cancer preventative, identify biomarkers of response or carcinogenesis and assess WB-MRI performance as a diagnostic tool for detecting cancers in participants with LFS by assessing yield and diagnostic accuracy of WB-MRI.DiscussionAlongside a parallel MILI study being conducted by collaborators at the National Cancer Institute (NCI), MILI is the first prevention trial to be conducted in this high-risk group. The MILI study provides a unique opportunity to evaluate the efficacy of metformin as a chemopreventive alongside exploring its mechanism of anticancer action and the biological process of mutated P53-driven tumourigenesis.Trial registrationISRCTN16699730. Registered on 28 November 2022. URL: https://www.isrctn.com/ EudraCT/CTIS number 2022-000165-41.

SWOG S2200 (PAPMET2): A phase II randomized trial of cabozantinib with or without atezolizumab in patients with advanced papillary renal cell carcinoma (PRCC).

TPS493 Background: The role of immune therapy is not established in PRCC. The S1500 (PAPMET) clinical trial established single agent cabozantinib as the standard of care for PRCC (PMID 33592176) with a median progression free survival (PFS) of 9.0 months compared to 5.6 months with sunitinib. Trials have shown activity of PD-(L)1 antagonists as monotherapy (PMID 33529058) or in combination with targeted therapy (PMID 34491815). In a single arm study of cabozantinib/nivolumab the median PFS was 12.5 months (PMID 35298296). There are no prior randomized studies of immune therapy in PRCC. Single arm trials often overestimate the true effect size (PMID 31218346), highlighting the unmet clinical need for a randomized clinical trial in PRCC. We hypothesize that the combination will have higher clinical activity than single agent cabozantinib. Methods: This is a prospective randomized phase II clinical trial conducted through the NCTN and led by SWOG. The primary endpoint is a comparison of PFS between cabozantinib and cabozantinib/atezolizumab. Secondary endpoints include comparison of objective response rate, overall survival and safety. Patients are treated with cabozantinib 60mg/day versus cabozantinib 60mg/day + atezolizumab 1200 mg q3 weeks. 200 patients will be enrolled and randomized 1:1. Key inclusion criteria include a pathologic confirmation of PRCC; presence of metastasis; 0-1 prior systemic lines of therapy for metastatic disease; and measurable disease as defined by RECIST 1.1 criteria. Prior treatment with adjuvant pembrolizumab is allowed if completed greater than 6 months before enrollment. Key exclusion criteria include clinically significant autoimmune disease; ongoing use of strong CYP3A4 inhibitors, strong CYP3A4 inducers. Planned correlatives include stool microbiome testing and genomic/transcriptomic analysis from blood and baseline tissue assays. Clinical trial information: NCT05411081 .

An Updated Comparison of Overall Survival with Brexucabtagene Autoleucel (Brexu-cel) CAR T-Cell Therapy (ZUMA-2) Versus Standard of Care (SCHOLAR-2) in Patients with Relapsed/Refractory Mantle Cell Lymphoma (R/R MCL) Previously Treated with a Covalent Bruton Tyrosine Kinase Inhibitor (BTKi)

An Updated Comparison of Overall Survival with Brexucabtagene Autoleucel (Brexu-cel) CAR T-Cell Therapy (ZUMA-2) Versus Standard of Care (SCHOLAR-2) in Patients with Relapsed/Refractory Mantle Cell Lymphoma (R/R MCL) Previously Treated with a Covalent Bruton Tyrosine Kinase Inhibitor (BTKi)