One-year Overall Survival Rates Research Articles

A prospective study of radiofrequency ablation combined with systematic neoadjuvant therapy in the treatment of recurrent hepatocellular carcinoma (RANT study).

e16240 Background: Radiofrequency ablation (RFA) is an important minimally invasive approach for recurrent HCC, but is hampered by the high recurrence rate and limited ablation volume for the tumor. This study aims to evaluate the efficacy and safety of systemic neoadjuvant therapy (tislelizumab combined with lenvatinib/bevacizumab) combined with RFA in the treatment of recurrent HCC. Methods: This prospective, single-arm, phase II trial enrolled patients with recurrent resectable HCC who has a history of liver resection or RFA (the number of lesions ≤ 3, the largest lesion ≤ 3 cm, as demonstrated by contrast enhanced CT/MRI). Prior to RFA, patients received tislelizumab (200 mg, q3w, iv) and lenvatinib (body weight≥60 kg, 12 mg; <60 kg, 8 mg, qd, po) or bevacizumab (15mg/kg) for two cycles. RFA was scheduled in one week after the systemic neoadjuvant therapy. After 4-8 weeks of surgery, patients continued to receive tislelizumab and lenvatinib /bevacizumab for 6 to 12 months. Primary endpoint was one-year relapse-free survival (RFS) rate and one-year overall survival (OS) rate. Secondary endpoints were objective response rate (ORR) by mRECIST, and adverse events (AE). Results: From November 2021 to October 2023, 20 patients (median age, 57 years) were enrolled, all Child-Pugh A and ECOG PS 0, mostly males (95%) and HBV infection (90.0%). 19 patients had received 2 cycles systemic neoadjuvant therapy and RFA was successfully performed, 1 patient achieved complete response after systemic treatment and didn't perform RFA. According to mRECIST, the ORR was 50% (95%CI: 27.20%-72.80%), and the DCR was 100 % (CR 1, PR 8, SD 11). After a median follow-up of 8.5 months (interquartile range 5-21 months), tumor recurrence was detected in 2 patients, 1 patient died of disease recurrence. The estimated 12-month RFS rate and OS rate were 76.9% (95%CI 31.2%, 94.3%) and 100%, respectively. Median RFS and OS were not reached. So far the safety of neoadjuvant treatment was satisfied, no grade 4 or above treatment-related-adverse events (TRAEs) were observed. Grade 3 TRAEs were reported in 3(13.04%) patients. Frequently occurring adverse eventswere grade 1-2, including total bilirubin increased (39.13%), elevated aspartate aminotransferase (30.43%), and elevated alanine aminotransferase (30.43%). Conclusions: Radiofrequency ablation combined with systematic neoadjuvant therapy exhibited promising efficacy and favorable safety for recurrent HCC. Clinical trial information: NCT05277675 .

Transarterial chemoembolization (TACE) combined with donafenib as first-line therapy for unresectable hepatocellular carcinoma (uHCC): A real-world clinical study.

e16145 Background: To evaluate the efficacy and safety of TACE combined with Donafenib, which is as a new tyrosine kinase inhibitors therapy recommended by the China liver cancer staging (CNLC) system for the treatment of unresectable hepatocellular carcinoma (uHCC). Methods: We conducted a single-center, retrospective study on patients diagnosed with uHCC treated by TACE plus Donafenib as the first-line therapy between May 2021 and September 2023 at The First Affiliated Hospital of Sun Yat-sen University. The primary outcomes evaluated in this study were progression-free survival (PFS) and overall survival (OS). Local response, one-year survival rate, safety and tolerability were the secondary outcomes. Results: All of 48 eligible patients by August, 2023, with the median age of 59 years. The clinical characteristics were as follows: BCLC stage A:2 (4.2%), B:16 (33.3%), and C:30 (62.5%); Child-Pugh class A:33 (68.8%) and B:15 (31.2%); ECOG PS 0: 27 (56.2%) and 1: 21 (43.7%). In this study, 10 (20.8%) patients had huge intrahepatic lesions, 15 (31.2%) subjects exhibited extrahepatic metastases at multiple sites, 19 (42.2%) patients presented with portal vein tumor thrombus, and 4 patients were diffuse-type HCC.107 TACE sessions were performed. Three patients had liver transplantation as frequent therapy, and histopathological examination of tissue from these subjects revealed complete necrotic foci. The median PFS was 12.8 months (95% CI: 8.66–NA) , mOS was not reached and the one-year OS rate was 87.5% (95% CI: 77%-97%) in the survival results. The tumor objective response rate was 58.3% with 14.5% complete response and 43.7% partial response based on mRECIST assessment. The disease control rate of the study group was 81.3%. The most common treatment-related adverse events (TRAEs) observed were elevated aspartate aminotransferase (AST) levels (75.0%), increase in bilirubin level (72.9%), elevated alanine aminotransferase (ALT) levels (54.2%), hand-foot syndrome (53.1%), diarrhea (29.1%), rashes (22.9%), hair loss (18.4%) and hypertension (12.5%). Twenty-three (46.9%) patients presented with grade 3 or 4 TRAEs including elevated AST levels (22.4%), elevated ALT levels (16.3%), increase in bilirubin level (4%), diarrhea (4%) and hypertension (2%). No Grade 5 TRAEs were observed. Conclusions: The combination of TACE and Donafenib presented good efficacy and tolerability, which could be potentially used as the first-line treatment of Chinese uHCC patients.

Nivolumab for mismatch-repair-deficient or hypermutated gynecologic cancers: a phase 2 trial with biomarker analyses

Programmed death-1 (PD-1) inhibitors are approved for therapy of gynecologic cancers with DNA mismatch repair deficiency (dMMR), although predictors of response remain elusive. We conducted a single-arm phase 2 study of nivolumab in 35 patients with dMMR uterine or ovarian cancers. Co-primary endpoints included objective response rate (ORR) and progression-free survival at 24 weeks (PFS24). Secondary endpoints included overall survival (OS), disease control rate (DCR), duration of response (DOR) and safety. Exploratory endpoints included biomarkers and molecular correlates of response. The ORR was 58.8% (97.5% confidence interval (CI): 40.7–100%), and the PFS24 rate was 64.7% (97.5% one-sided CI: 46.5–100%), meeting the pre-specified endpoints. The DCR was 73.5% (95% CI: 55.6–87.1%). At the median follow-up of 42.1 months (range, 8.9–59.8 months), median OS was not reached. One-year OS rate was 79% (95% CI: 60.9–89.4%). Thirty-two patients (91%) had a treatment-related adverse event (TRAE), including arthralgia (n = 10, 29%), fatigue (n = 10, 29%), pain (n = 10, 29%) and pruritis (n = 10, 29%); most were grade 1 or grade 2. Ten patients (29%) reported a grade 3 or grade 4 TRAE; no grade 5 events occurred. Exploratory analyses show that the presence of dysfunctional (CD8+PD-1+) or terminally dysfunctional (CD8+PD-1+TOX+) T cells and their interaction with programmed death ligand-1 (PD-L1)+ cells were independently associated with PFS24. PFS24 was associated with presence of MEGF8 or SETD1B somatic mutations. This trial met its co-primary endpoints (ORR and PFS24) early, and our findings highlight several genetic and tumor microenvironment parameters associated with response to PD-1 blockade in dMMR cancers, generating rationale for their validation in larger cohorts.ClinicalTrials.gov identifier: NCT03241745.

Safety and Efficacy of Moderate-Intensity Stereotactic Body Radiation Therapy for Ultra-Central Lung Tumor.

Background and Objectives: Ultra-central (UC) lung tumors are defined as those abutting the proximal bronchial tree. Stereotactic body radiation therapy (SBRT) for UC tumors is difficult because of concerns about severe toxicities. Therefore, we report the safety and efficacy of moderate-intensity SBRT for UC tumors at our institution. Materials and Methods: From January 2017 to May 2021, we treated 20 patients with UC tumors with SBRT at a dose of 45-60 Gy in 10 fractions. The primary endpoints were local control (LC) and overall survival (OS). Results: The median follow-up time was 15.8 months (range: 2.7-53.8 months). Ten of the 20 patients (50.0%) showed a complete response, five (25.0%) had a partial response, two (10.0%) had stable disease, and three (15.0%) showed progressive disease (PD). The response and disease control rates were 75.0% and 85.0%, respectively. Patients with PD showed local progression at median 8.3 months (range: 6.8-19.1 months) after SBRT. One-year and 2-year OS rates were 79.4% and 62.4%, respectively. One-year and 2-year LC rates are 87.1% and 76.2%, respectively. Eight patients died due to a non-radiation therapy related cause. One patient experienced grade 5 massive hemoptysis 6 months after SBRT, resulting in death. One patient experienced grade 2 esophageal pain and two experienced grade 2 radiation pneumonitis. Otherwise, no grade 3 or higher toxicities were reported. Conclusions: Moderate-intensity SBRT offers effective control of UC tumors and is a well-tolerated treatment for such tumors.

Prognostic Insights and Survival Analysis of Gallbladder Cancer in Bihar, India: a Prospective Observational Study Emphasizing the Impact of Surgical Intervention on Overall Survival.

The aim of this study was to determine the 1- and 3-year overall survival rates. This prospective observational study was conducted at a tertiary care center in Bihar state, India. The study analyzed 228 patients in Bihar with a median age at diagnosis of 55 ± 12.05years. The most common symptoms included upper abdominal pain (26.3%), weight loss (14%), and ascites (13.6%). The majority of patients presented at stage IV (72.8%), with liver metastasis being prevalent (61.4%). Interventional biliary drainage was performed in 9.6% of cases, and systemic chemotherapy was received by 84.64%, while 15.36% opted for best supportive care. Univariate Cox regression analysis identified Eastern Cooperative Oncology Group (ECOG) performance status, stage, gallstone disease, and surgical intervention as significant risk factors influencing overall survival (OS) (p < 0.001). Multivariate Cox regression analysis confirmed ECOG performance status (p < 0.001), stage (p = 0.039), and surgical intervention (p = 0.038) as independent factors impacting OS. One-year OS rates for stages II, III, and IV were 100%, 97%, and 44%, respectively, while 3-year OS rates were 29%, 4%, and 0%. Surgical intervention significantly influenced OS (p < 0.001). OS for surgical intervention was 28months, and for inoperable cases, it was 12months. One- and 3-year OS for surgical intervention were 95% and 11%, while for inoperable cases, they were 41% and 0%, respectively. Patients with gallbladder cancer, particularly in Bihar's Gangetic plains, face poor survival, especially with advanced disease. Adequate surgery improves outcomes, prompting a call for enhanced strategies, particularly for locally advanced GBC.

Transarterial Chemoembolization with Epirubicin-Loaded Microspheres for Hepatocellular Carcinoma: A Prospective, Single-Arm, Multicenter, Phase 2 Study (STOPPER Trial)

PurposeWhile the role of drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) is established, questions regarding appropriate bead size for use in patients remain. This trial evaluated the effectiveness and safety of DEB-TACE using small-size (≤ 100 μm) microspheres loaded with epirubicin.Materials and MethodsThis prospective, single-arm, multicenter study enrolled patients diagnosed with HCC who underwent DEB-TACE using 40 (range, 30–50), 75 (range, 60–90), or 100 (range, 75–125) μm epirubicin-loaded microspheres (TANDEM microspheres, Varian Medical). Bead size was at the discretion of treating physicians and based on tumor size and/or vascular structure. The primary outcome measure was 6-month objective response rate (ORR). Secondary outcome measures were 30-day and 3-month ORR, time to tumor progression and extrahepatic spread, proportion of progression-free survival and overall survival (OS) at one year, and incidence of treatment-associated adverse events.ResultsData from 108 patients from ten centers was analyzed. Six-month ORR was 73.3 and 71.3% based on European association for the study of the liver (EASL) and modified response evaluation criteria in solid tumors (mRECIST) criteria, respectively. Thirty-day ORR was 79.6% for both EASL and mRECIST criteria with 3-month ORR being 80.0 and 81.0%, respectively, for each criteria. One-year PPF and OS rate were 60.3 and 94.3%. There was a total of 30 SAEs reported to be likely to definitely associated with microsphere (n = 9), epirubicin (n = 9), or procedure (n = 12) with none resulting in death.ConclusionDEB-TACE using epirubicin-loaded small-sized (≤ 100 μm) microspheres demonstrates promising local tumor control and acceptable safety in patients with HCC.Trial RegistrationClinicaltrials.gov NCT03113955; registered April 14, 2017.Trial Registration Clinicaltrials.gov NCT03113955; registered April 14, 2017.Level of evidence2, Prospective, Non-randomized, Single-arm, study.Graphical

Prognostic factors and clinical survival outcome in patients with primary mediastinal diffuse large B-cell lymphoma in rituximab era: A population-based study.

The goal of this study was to investigate the clinical characteristics, prognostic variables, and survival of patients with primary mediastinal diffuse large B cell lymphoma (PMBCL) in the rituximab era. The Surveillance, Epidemiology, and End Results (SEER) database was used to identify PMBCL patients diagnosed between 2000 and 2019. The Kaplan-Meier (K-M) technique and log-rank test were used to assess overall survival (OS) and disease-specific survival (DSS). The independent prognostic variables for OS and DSS were identified using univariate and multivariate Cox regression analysis. Nomograms were created to predict survival prospects according to identified prognostic indicators. Totally, 841 patients were enrolled with PMBCL. One-year, 5-year, and 10-year OS rates were 93.99%, 85.04%, and 81.76%, and the corresponding DSS rates were 95.27%, 87.37%, and 85.98%. The results of multivariate Cox regression analysis demonstrated that age, years of diagnosis, Ann arbor staging, and chemotherapy were independent prognostic factors for survival. Nomograms designed exclusively for PMBCL were created to forecast the likelihood of 1-year, 5-year, and 10-year OS and DSS, respectively. The Harrell concordance index (C-index) for the nomograms predictions of OS and DSS were 0.704 and 0.733, respectively, which showed the established model harboring powerful and accurate performance. The present study revealed that incidence of PMBCL has been consistently rising over the last 20 years. Simultaneously, survival rates have improved tremendously. Rituximab based immunochemotherapy has emerged as an effective treatment option, leading to enhanced OS and DSS outcomes. Furthermore, the nomograms specifically developed for PMBCL have demonstrated robustness and accuracy in forecasting OS and DSS rates at 1, 5, and 10 years. These predictive tools can be valuable for clinicians in accurately estimating prognosis and establishing personalized treatment plans and follow-up protocols.

Retrospective assessment of neoadjuvant camrelizumab combined with induction chemotherapy: efficacy in laryngeal preservation for advanced hypopharyngeal and laryngeal squamous cell carcinoma

BackgroundHypopharyngeal and laryngeal squamous cell carcinoma (SCC) account for 25–30% of head and neck SCC. Total laryngectomy, while effective, compromises the quality of life. Immune checkpoint inhibitors such as Camrelizumab offer potential in laryngeal preservation. The study investigated Camrelizumab combined with TP regimen as a neoadjuvant therapy for laryngeal preservation in advanced hypopharyngeal and laryngeal SCC.MethodsA retrospective study was conducted at Sun Yat-sen University Cancer Center on patients diagnosed with locally advanced SCC of the hypopharynx and larynx from October 1, 2019, to October 25, 2022. The efficacy of a first-line treatment combining Camrelizumab (200 mg) and TP regimen (Albumin-bound paclitaxel at 260 mg/m2 and Cisplatin at 60 mg/m2) was evaluated using RECIST 1.1 criteria. Outcomes included overall survival (OS), progression-free survival (PFS), laryngectomy-free survival (LFS), and response rates.ResultsOf the 71 included patients, the median age was 60.7 years. Post the first-line treatment, 90.1% demonstrated an overall response. The one-year and two-year OS rates were 91.5% and 84.3%, respectively. One-year and two-year PFS rates were 92.9% and 83.9%, respectively, with LFS at 85.6% and 73.2%. The initial T4 stage as significantly associated with reduced OS and LFS. Skin reaction was the predominant adverse event.ConclusionThe Camrelizumab-TP regimen demonstrated promising results for advanced hypopharyngeal/laryngeal SCC patients, exhibiting high response rates, OS, and LFS, positioning it as a potential primary option for laryngeal preservation. Further comprehensive, randomized controlled studies are imperative to validate these initial observations and elucidate the regimen's full clinical efficacy in optimizing laryngeal outcomes.

Neoadjuvant PD-1 Plus Chemotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma.

Clinical studies have shown that programmed cell death-1 (PD-1) inhibitors can activate T cells and inhibit cancer growth. Therefore, the use of a PD-1 inhibitor plus chemotherapy as neoadjuvant chemotherapy for locally advanced esophageal cancer is worth further exploration. Patients with locally advanced esophageal squamous cell carcinoma were enrolled in this study to receive two cycles of a preoperative combination of toripalimab, paclitaxel, and cisplatin. Efficacy was evaluated after two treatment cycles. The patients' postoperative pathological staging was analyzed and compared. Surgery was performed within 42 days of the start date of the last chemotherapy cycle. Neoadjuvant immunochemotherapy achieved a high pathologic complete response (pCR) rate (29.0%), major pathological response rate (41.9%), and objective response rate (80.6%) and demonstrated statistically significant downstaging after neoadjuvant therapy (P < .05) with manageable treatment-related adverse effects. No significant association was found between PD-L1 level and pCR (P = .365). In addition, R0 resection was achieved in all 31 (100%) patients during surgery. For all the included patients, the one-year progression-free survival rate was 87.1% (95% CI: 75.3%-98.9%), the one-year overall survival (OS) rate was 96.8% (95% CI: 79.8%-95.9%), and the two-year OS rate was 83.9% (95% CI: 71.6%-92.2%). Our findings indicate that this combination may be a potential neoadjuvant therapy regimen in this setting.

Linperlisib in Conjunction with Gemcitabine and Oxaliplatin in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Multicenter, Single-Arm Phase Ib/II Study

Background: Diffuse large B-cell lymphoma (DLBCL) represents the most common subtype of non-Hodgkin lymphoma (NHL), comprising approximately 30-40% of new NHL cases. Although immunochemotherapy is the current front-line treatment for DLBCL, nearly 40% of patients will face disease relapse or refractoriness to the initial therapy, with a suboptimal prognosis. Gemcitabine in combination with oxaliplatin (GEMOX) offers an established treatment regimen with a manageable side-effect profile, thus providing a viable backbone for innovative treatment combinations. Linperlisib, a selective PI3Kδ inhibitor, has demonstrated its ability to inhibit the growth of PI3Kδ-expressing human tumor cells, as evidenced by both in vitro and in vivo studies. The tolerability, pharmacokinetics, and preliminary efficacy of linperlisib were affirmed in a preceding phase I study, laying the groundwork for its further exploration in patients with relapsed or refractory (r/r) DLBCL. This study aimed to investigate the efficacy and safety of combining linperlisib with GEMOX in treating r/r DLBCL patients. Methods: In this multicenter, single-arm phase Ib/II trial (NCT04500561), histologically confirmed r/r DLBCL patients across six Chinese centers were enrolled and received oral linperlisib (80 mg/day) alongside intravenous GEMOX (gemcitabine 1000 mg/m 2 on day 1, and oxaliplatin 100 mg/m 2 on day 2) every three weeks, with GEMOX administered for a maximum of six cycles. The primary endpoint was the objective response rate (ORR), with secondary outcomes including disease control rate (DCR), time to response (TTR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results: Between September 2020 and June 2021, 39 patients were enrolled and received the study treatment, all of whom were included in the efficacy and safety analysis. By the data cutoff in February 2023, and after a median follow-up of 24.1 months, three patients were still on treatment. The ORR reached 53.8% (95%CI: 37.2, 69.9), and the DCR was recorded at 64.1% (95%CI: 47.2, 78.8) (Figure 1). The median TTR was 1.3 months (range: 1.2-4.0). The median DOR stood at 5.7 months (95%CI: 4.3-9.1), and the median PFS was 5.4 months (95%CI: 1.8-6.7). The median OS had not yet been reached by the cutoff, with the one-year OS rate standing at 65.5% (95%CI: 48.1-78.3). Stratification by subtype revealed an ORR of 66.7% (6/9) among germinal center B-cell like (GCB) DLBCL patients compared to 40% (10/25) among non-GCB DLBCL patients. Median PFS was reported at 3.0 and 3.4 months for GCB and non-GCB DLBCL patients, respectively. The most prevalent grade 3 or higher treatment-related adverse events included decreases in neutrophil count (46.2%), platelet count (41.0%), and white blood cell count (28.2%). Conclusion: The combination of linperlisib with GEMOX exhibits a favorable safety profile and promising clinical efficacy in patients with r/r DLBCL who have received a median of two prior systemic therapies. These findings support the potential role of linperlisib combined with GEMOX as an active and safe therapeutic option for patients with r/r DLBCL, and set a foundation for further research into linperlisib's potential in combination with other treatment regimens.

PD-1 Inhibitors combined with paclitaxel (Albumin-bound) and cisplatin for larynx preservation in locally advanced laryngeal and hypopharyngeal squamous cell carcinoma: a retrospective study.

laryngeal and hypopharyngeal squamous cell carcinoma (SCC) is a common head and neck cancer with significant impact on quality of life due to its crucial roles in vocalization, airway protection, and swallowing. This retrospective study aims to evaluate the efficacy and larynx organ preservation of neoadjuvant treatment with PD-1 inhibitors in combination with paclitaxel (Albumin-bound) and cisplatin for locally advanced laryngeal and hypopharyngeal SCC. Medical records of consecutive patients diagnosed with histologically or cytologically confirmed locally advanced SCC of the larynx and hypopharynx, who received PD-1 inhibitor therapy at a single tertiary care center, were reviewed from January 1, 2019, to December 15, 2022. The patients were treated with a combination of PD-1 inhibitors, paclitaxel (Albumin-bound) 260mg/m2, and cisplatin 60mg/m2 (TP) as their first-line therapy. Survival outcomes, laryngectomy-free survival (LFS) rates and response rates were assessed. The study cohort comprised 156 patients, predominantly male, with a median age of 60.4 years. The estimated one-year overall survival (OS) rate was 94.1%, two-year OS rate was 82.5%, one-year progression-free survival (PFS) rate was 80.4%, and two-year PFS rate was 66.3%. The one-year LFS was 86.4%, and the two-year LFS rate was 73.0%. The overall response rate after TP + PD-1 inhibitors therapy was 88.5%. Common treatment-associated adverse events included rash, thyroid function abnormalities, myelosuppression, and colitis. Neoadjuvant therapy with PD-1 inhibitors in combination with paclitaxel (Albumin-bound) and cisplatin showed promising efficacy and tolerability for larynx preservation in locally advanced laryngeal and hypopharyngeal SCC. The high response rates and favorable survival outcomes suggest this approach as a potential treatment option. Prospective randomized controlled trials are needed to further validate these findings and establish the role of immunotherapy in larynx preservation.

Estimating the Survival Rate in Glioblastoma Multiforme Patients who Received a Peptide Vaccine: A Systematic Review and Meta-analysis.

Glioblastoma Multiforme (GBM) has a poor prognosis, with current treatments providing no advantage in terms of survival. Certain new immunotherapy methods, such as peptide vaccines, have been used in clinical trials. In this meta-analysis, the effectiveness of peptide vaccinations on the survival rate of GBM patients was studied. A comprehensive search was carried out using three electronic databases: PubMed, Scopus, and ISI. The purpose of this research was to assess Overall Survival (OS). The pooled overall one-year and two-year survival rates in GBM with peptide vaccination were calculated using the general inverse variance technique as random effects hazard ratios (HRs). In the study, subgroups of countries were compared with each other. Japan had the highest one-year survival rate, and the US had the highest two-year survival rate. With 95% Confidence Intervals (CIs), the one-year OS rate in GBM patients treated with peptide vaccination increased significantly, but the two-year survival rate did not increase. As a result, while additional research is needed, it cannot be concluded that it is an effective therapy for GBM. Our study found that while peptide vaccination treatment did not increase second-year survival, it improved first-year survival. More research needs to be done to find effective vaccinebased treatments for GBM that can help patients survive longer.

Efficacy and safety of osimertinib for leptomeningeal metastases from EGFR-mutant non-small cell lung cancer: a pooled analysis

BackgroundThe aim of this study was to evaluate the efficacy and safety of osimertinib for the treatment of leptomeningeal metastases (LM) from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC).MethodsWe conducted a systematic review and meta-analysis to aggregate the clinical outcomes of patients with LM from EGFR-mutant NSCLC treated with osimertinib. A comprehensive literature search for published and unpublished studies was implemented in April 2021 of PubMed, EMBASE, the Cochrane Library, and several international conference databases, in accordance with the PRISMA guidelines. Meta-analysis of proportions was conducted to calculate the pooled rate of overall response rate (ORR), disease control rate (DCR), one-year overall survival (OS), and adverse events (AEs).ResultsA total of eleven studies (five prospective and six retrospective) including 353 patients were included. The majority of patients (346/353, 98.0%) received osimertinib as ≥ 2nd-line treatment for LM, either at a dosage of 80 mg (161/353, 45.6%) or 160 mg (191/353, 54.1%). The pooled rates of ORR and DCR were 42% (95% CI 24% to 59%) and 93% (95% CI 88% to 97%), respectively. The pooled one-year OS rate was 59% (95% CI 53% to 65%) in 233 patients from five studies. The highest incidence of AEs of all grades was rash (53%), followed by diarrhea (45%), paronychia (35%), decreased appetite (35%), and dry skin (27%), based on data from four studies.ConclusionsOur study highlighted and confirmed the meaningful efficacy and a manageable safety profile of osimertinib for the treatment of LM from EGFR-mutant advanced NSCLC.

Fractionated versus staged gamma knife radiosurgery for mid-to-large brain metastases: a propensity score-matched analysis.

To compare treatment results between fractionated gamma knife radiosurgery (f-GKRS) and staged gamma knife radiosurgery (s-GKRS) for mid-to-large brain metastases (BMs). We retrospectively analyzed data of patients with medium (4-10 mL) to large (> 10 mL) BMs who underwent s-GKRS or f-GKRS between March 2008 and September 2022. Patients were treated with (i) s-GKRS before May 2018 and (ii) f-GKRS after May 2018. Patients who underwent follow-up magnetic resonance imaging at least once were enrolled. Case-matched studies were conducted by applying propensity score matching to minimize treatment selection bias and potential confounding. Local control (LC) was set as the primary endpoint and overall survival (OS) as the secondary endpoint. This study included 129 patients with 136 lesions and 70 patients with 78 lesions who underwent s-GKRS and f-GKRS, respectively. Overall, 124 lesions (62 lesions in each group) were selected in the case-matched group. No differences were observed in the 6-month and 1-year cumulative incidences of LC failure between the s-GKRS and f-GKRS groups (15.6% vs. 15.9% at 6 months and 25.6% vs. 25.6% at 1 year; p = 0.617). One-year OS rates were 62.6% (95% confidence interval [CI]: 45.4-75.7%) and 73.9% (95% CI: 58.8-84.2%) in the s-GKRS and f-GKRS groups, respectively. The post-GKRS median survival time was shorter in the s-GKRS group than in the f-GKRS group (17 vs. 36 months), without significance (p = 0.202). This is the first study to compare f-GKRS and s-GKRS in large BMs. Fractionation is as effective as staged GKRS for treating mid-to-large BMs.

Efficacy and safety of donafenib combined with transcatheter arterial chemoembolization (TACE) and anti-PD1 antibody for the treatment of unresectable hepatocellular carcinoma (uHCC): A retrospective study.

e16120 Background: For unresectable hepatocellular carcinoma (uHCC), the efficacy of TACE monotherapy is not satisfactory. It has recently been reported that molecular targeted drugs combined with anti-PD1 antibody and TACE exhibit improved anti-tumor efficacy compared with monotherapy. Donafenib is a new generation of multi-kinase inhibitor which is approved as the first-line treatment for uHCC. This study aimed to explore the efficacy and safety of the combination therapy of donafenib, anti-PD1 monoclonal antibody and TACE in patients with uHCC. Methods: This was a single-center retrospective study, and involved patients with uHCC who received donafenib (200 mg po bid) combined with TACE and anti-PD1 monoclonal antibody or donafenib (200 mg po bid) combined with TACE at Shanghai Eastern Hepatobiliary Surgery Hospital from September 2021 to September 2022. All patients had at least one measurable lesion defined by mRECIST criteria. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) data of patients were collected and analyzed. Results: A total of 34 patients with uHCC were included and had a median age of 56 years (32–81 years). Of these patients, 3 (9%) were classed as BCLC stage B, 31 (91%) were BCLC stage C. All 34 patients were complicated with HBV infection. First-line treatment was administered to 24 patients (71%), among which 21 patients received donafenib combined with TACE and anti-PD1 antibody. 3 patients were treated with donafenib combined with TACE. The remaining 10 patients (19%) received second-line treatment, among which 7 patients were treated with donafenib combined with TACE and anti-PD1 antibody. 3 patients received donafenib combined with TACE. There were 14 patients (41%) with baseline AFP ≥400 ng/mL. At data cut-off, the median follow-up time was 5 months [95% CI: 3.42-6.58]. The best overall response rate (BOR) was complete response in 5 patients (14.7%), partial response in 13 patients (38.2%), stable disease in 10 patients (29.4%), and progressive disease in 6 patients (17.6%). The ORR was 52.9% (95%CI: 36.7–68.6%) and DCR was 82.4% (95%CI: 66.5–91.7%). The median PFS and median OS were not reached, the one-year PFS rate was 61.6% (95%CI: 38–78.7%), and the one-year OS rate was 83.1% (95%CI: 56.1–95.2%). The ORR (58%) and DCR (87.5%) of patients receiving first-line treatment were better compared with those of patients receiving second-line treatment (40% and 70%, respectively). Treatment-related adverse events (TRAE) were reported by 30 patients (88.2%), of which 7 patients (20.6%) had grade 3 TRAE. No grade 4 or 5 TRAE was reported. Conclusions: Donafenib combined with TACE and anti-PD-1 antibody exhibited encouraging efficacy and favorable safety profile in patients with uHCC.

Preliminary efficacy and safety of camrelizumab plus metronomic oral vinorelbine as first-line therapy for people aged 70 and above with advanced non-small cell lung cancer (NSCLC) from a phase II trial.

e14677 Background: Traditional platinum-based combination chemotherapy used as the standard first‐line treatment for advanced NSCLC poses potential safety risk for patients (pts) aged 70 years and above. Moreover, data on immune checkpoint inhibitors treating older pts with lung cancer in the current pivotal trials is limited. Metronomic chemotherapy (MCT) is the frequent administration of chemotherapy drugs at lower doses each time. Compared with traditional chemotherapy, MCT shows better safety profile and antitumor angiogenesis and immunomodulatory effects. Camrelizumab, an anti-PD-1 inhibitor, demonstrated encouraging efficacy in NSCLC (CameL study and CameL-sq study). Here, we designed a phase II trial to evaluate the efficacy and safety of camrelizumab plus metronomic oral vinorelbine (mOV) as first-line therapy for Chinese older pts with advanced NSCLC. Methods: Key inclusion factors were pts aged 70 years and above, histologically or cytologically confirmed unresectable stage III and IV NSCLC without positive EGFR mutation, ALK fusions or ROS1 fusions, ECOG performance status 0-2, no previous systematic treatment. Pts received camrelizumab (200mg, D1, q3w) combined with mOV (30mg, tiw1, day 1-3-5 per week) for 6 cycles, followed by camrelizumab monotherapy maintenance until disease progression or intolerable side effects. The primary endpoint was progression free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and safety. Results: From March 2021 to November 2022, 12 pts were evaluable for inclusion in the study. The median age was 77 (range: 70-85) with 8 (67%) males. Median follow-up was 7.2 months (range 2.8 months-22.1 months). The median PFS was 9.3 months (95%CI: 3.9 months-14.7 months). The one-year OS rate was 66.3%. The ORR and DCR were 50% (95%CI: 25.4%-74.6%) and 83.3% (95%CI: 50.9%-90.1%), respectively. Pts with positive or negative PD-L1 responded similarly to the treatment (respectively at 5/8 and 1/2 on ORR). The median OS and DoR have not been reached. Adverse events (AEs) with any grade were observed in 10 (83.3%) pts, of which grade III-IV AEs were observed in 2 (16.7%) pts with neutropenia and interstitial pneumonia, respectively. Immune-related adverse events (irAEs) occurred in 3 (25%) pts, of which grade III-IV irAEs occurred in one (8.3%) patient with interstitial pneumonia. No grade 5 adverse event happened. Conclusions: The regimen of camrelizumab plus mOV for the first-line therapy for older NSCLC pts showed initial promising efficacy and safety profile, which suggests it is worth further exploration. Clinical trial information: ChiCTR2100049487 .

A retrospective study of the efficacy and safety of donafenib combined with TACE as adjuvant therapy in patients with high-risk recurrence factors after hepatocellular carcinoma surgery.

e16121 Background: Surgical resection is the most important treatment for patients with hepatocellular carcinoma (HCC) to obtain long-term survival. However, the 5-year recurrence rate after hepatectomy is as high as 40%-60% and above. Reducing the postoperative recurrence rate is the key to improve the overall efficacy of HCC. This study aimed to evaluate the efficacy and safety of donafenib combined with TACE as adjuvant therapy in HCC patients with high-risk recurrence factors after surgical resection. Methods: This single-center retrospective study enrolled primary HCC patients with high-risk recurrence factors who underwent surgical resection at Shanghai Eastern Hepatobiliary Surgery Hospital from April 2021 to October 2022. High-risk recurrence factors included: the number of tumors ≥ 3, tumor diameter ≥ 5 cm, portal vein tumor thrombus, microvascular invasion (MVI) and satellite lesions. Patients received adjuvant therapy of donafenib combined with TACE after surgery. Patients’ demographic characteristics, etiological characteristics, 1-year recurrence-free survival rate (RFSR), recurrence-free survival (RFS), overall survival (OS), and treatment-related safety were analyzed. Results: A total of 40 patients were enrolled with a median age of 55.5 years (21-78), 39 patients (97.5%) in BCLC stage B and 1 patient (2.5%) in BCLC stage C. 33 patients (82.5%) were co-infected with HBV. All 40 patients had ECOG PS scores of 0 and Child-Pugh scores of A. A total of 34 patients (85%) with MVI were pathologically reported after surgery, 23 patients (57.5%) with tumor diameter ≥5cm, 9 patients (22.5%) with portal vein cancer thrombus, and 6 patients (15%) with satellite lesions. All patients received at least one TACE treatment after surgery, 31 patients (77.5%) received the TACE treatment one month after surgery, and 9 patients (22.5%) received the TACE treatment within one month after surgery. The initial dose of donafenib was 200mg/day. As of the cut-off date of data collection, the median follow-up time was 9 months (95%CI: 7.73-10.27), 4 patients relapsed and 2 patients died. The median RFS was 18 months (95% CI: 13.673-22.327), the one-year RFSR was 83.3% (95% CI: 61.9%-93.8%), and the one-year OS rate was 95.8% (95% CI: 75.2%-99.6%). 21 patients (52.5%) had combined treatment-related adverse events (TRAE), of which 4 patients (10%) had Grade 3 TRAE and no grade 4 or 5 TRAE were reported. Common adverse events included hand-foot skin reaction (9 patients, 22.5%), diarrhea (9 patients, 22.5%), rash (5 patients, 12.5%), hypertension, and gastrointestinal reactions (2 patients each, 5%). Conclusions: Donafenib combined with TACE was used for adjuvant therapy in patients with high-risk recurrence of HCC, which has a high one-year recurrence-free survival rate and was well tolerated.

Long-term efficacy of BRAFi/MEKi rechallenge in metastatic melanoma: Report of 9 years of clinical practice.

e21550 Background: First line BRAFi/MEKi therapy in metastatic melanoma eventually result in drug resistance and disease progression. Because drug resistance develops at least partially by epigenetic mechanisms, it may potentially be reversed after BRAFi/MEKi discontinuation. Therefore we aim to explore the clinical efficacy of BRAFi/MEKi rechallenge in 3 line treatment. Moreover the reports on the efficacy of BRAFi/MEKi after immunotherapy were contradictory, so we enrolled patients treated sequentially to explore this clinical scenario. Methods: In country-wide multicenter retrospective analysis 86 patients with metastatic BRAF-mutated melanoma were enrolled since 1/Jan/2014. Patients were treated with 1st line BRAFi/MEKi, 2nd line immunotherapy (anti-PD-1 or anti-CTLA-4) and were rechallenged with BRAFi/MEKi. Survival analyses were performed using the Kaplan-Meier method, log-rank and chi-square tests were used for comparison between groups. Data cut-off was 31/Dec/2022. Results: Median age at BRAFi/MEKi rechallenge was 50 (range: 20-81 y/o). Median overall survival (OS) from the start of the first BRAFi/MEKi therapy and from rechallenge BRAFi/MEKi treatment was 34 and 9 months, respectively; whereas median progression-free survival (PFS) was 10.5 and 4.4 months respectively. At the time of analysis 88% progressed on third line therapy and 78% patients died. Six-month, one-year, and two-year OS rates were: 99%, 93% and 70% on first line treatment; and 65%, 40% and 2% on BRAFi/MEKi rechallenge. Objective response rate and disease control rate on first line BRAFi/MEKi and rechallenge were 57% and 28%; and 91% and 64%, respectively. A lower toxicity rate was noted with BRAFi/MEKi rechallenge. The most common treatment sequence was dabrafenib/trametinib – immunotherapy – encorafenib/binimetinib. Conclusions: Rechallenge with BRAFi/MEKi after second line immunotherapy results in a clinically significant benefit in majority of eligible patients. Third line treatment should be considered for fit patients. [Table: see text]

Molecular genetic and cytofluorimetric prognostic factors in the development of acute myeloid leukemia relapse in children after allogeneic hematopoietic stem cell transplantation

Relapse of acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains one of the main causes of reduced long-term survival. Modern methods for predicting the risk of AML relapse after allo-HSCT take into account the data on the pre-transplant level of minimal residual disease (MRD) determined by flow cytometry and molecular biological studies of recurrent genetic abnormalities, which are currently widespread in clinical practice. Recent studies of the expression of genes characteristic of leukemic stem cells (LSCs) have shown prognostic significance for children with AML in relation to treatment response and the risk of relapse. The study of LSC persistence in order to predict the risk of recurrence after allo-HSCT in children with AML in addition to standard MRD detection methods may be of great importance. The aim of the work was to evaluate the impact of MRD status, both using classic methods and taking into account the genes characteristic of LSC, on the results of allo-HSCT in children with AML. The study was approved by the Independent Ethics Committee and the Scientific Council of the I.P. Pavlov First Saint Petersburg State Medical University of Ministry of Healthcare of the Russian Federation. To assess MRD using standard diagnostic methods, we analyzed the data of 95 children with AML in their 1st–2nd remission (cohort 1). MRD status was negative in 67 (70.6 %) patients; in 28 (29.4 %) children, MRD status was positive according to molecular genetic studies and / or immunophenotyping results. For pre-transplant evaluation of the expression of genes characteristic of LSC, we investigated bone marrow samples of 50 patients (cohort 2) using real-time polymerase chain reaction. The DNMT3B, GPR56, CD34, SOCS2, SPINK2, FAM30A, and ABL genes were studied by real-time polymerase chain reaction, followed by calculation of the pLSC6 value using the formula: DNMT3b × 0.189 + GPR56 × 0.054 + CD34 × 0.0171 + SOCS2 × 0.141 + SPINK2 × 0.109 + FAM30A × 0.0516. At the time of allo-HSCT, 37 (74 %) children with AML were in their 1st or 2nd remission of the disease, 13 (26 %) were out of the 1st–2nd remission. With a median follow-up of 5 years in the group of patients with a positive MRD status, determined by standard methods (cohort 1), overall survival (OS) was 67.9 % vs 73.1 % for patients with a negative MRD status (p = 0.83). The cumulative incidence of relapse was 50 % and 22 %, respectively; p = 0.012. When assessing the level of expression of genes characteristic of LSC (cohort 2), a pLSC6 level was above the median in 18/37 (49 %) patients. The results of linear regression showed that the pre-transplant level of expression of genes characteristic of LSC was not associated with the number of blasts/MRD (odds ratio 1.002; 95 % confidence interval 0.979–1.025). One-year OS rates did not differ significantly in children in the 1st–2nd remission of AML, depending on pLSC6 level: 84.2% in patients with low pLSC6 and 72.2 % – with high pLSC6 (p = 0.4), event-free survival in the corresponding groups – 68.4 % and 61.1 %, respectively (p = 0.34). The cumulative incidence of early relapse after allo-HSCT in the group of AML patients with a high pLSC6 score was significantly higher than in children with a low pLSC6 score before allo-HSCT (22 % and 0 %, respectively; p = 0.03). MRD does not have a statistically significant effect on OS. However, MRD positivity before allo-HSCT increases cumulative incidence of relapse. The level of expression of genes characteristic of LSC, determined before allo-HSCT, showed a prognostic significance in relation to the development of early AML relapse after allo-HSCT.

The safety and feasibility of three-dimensional visualization planning system for CT-guided microwave ablation of stage I NSCLC (diameter ≤2.5 cm): A pilot study.

Microwave ablation (MWA) of lung tumors is a technique that is dependent on the ablationist's level of expertise. The selection of the optimum puncture path and determination of appropriate ablative parameters is the key to the success and safe of the procedure. The objective of this study was to describe the clinical use of a novel three-dimensional visualization ablation planning system (3D-VAPS) for aided MWA of stage I non-small cell lung cancer (NSCLC). This was a single-arm, single-center, retrospective study. From May 2020 to July 2022, 113 consented patients with stage I NSCLC received MWA treatment in 120 MWA sessions. The 3D-VAPS was used to determine that: (1) the overlap between the gross tumor region and simulated ablation; (2) the proper posture and appropriate puncture site on the surface of the body; (3) the puncture path; and (4) presetting preliminarily ablative parameters. Patients were monitored with contrast-enhanced CT scans at 1, 3, and 6 months, as well as every 6 months following that. The primary endpoints were technical success and a complete ablation rate. Local progression-free survival (LPFS), overall survival (OS), and comorbidities were secondary study objectives. The mean diameter of tumors was 1.9 ± 0.4 cm (range 0.9-2.5 cm). The mean duration was 5.34 ± 1.28 min (range 3.0-10.0 min). The mean power output was 42.58 ± 4.23 (range 30.0-50.0W). The median follow-up time was 19.0 months (6.0-26.0 months). The technical success rate was 100%. Three-month after the procedure, the complete ablation rate was 97.35%. 6, 9, 12, and 24 months LPFS rates were 100%, 98.23%, 98.23%, and 96.46%, respectively. One-year and 2-year OS rates were 100% and 100%. There were no patients who died both during the procedure and after the MWA of 30 days. The complications after MWA included pneumothorax (38.33%), pleural effusion (26.67%), intrapulmonary hemorrhage (31.67%), and pulmonary infection (2.50%). This research describes and confirms that 3D-VAPS is a feasibility and safe method for MWA of stage I NSCLC treatment. 3D-VAPS may be helpful to optimize the puncture path, assess reasonable ablative parameters, and minimize complications.