Patients with locally advanced cervical cancer (LACC) treated with concurrent chemoradiotherapy (CCRT) show substantial heterogeneity in survival outcomes, whereas the comparative prognostic value of systemic inflammatory and nutritional biomarkers remains unclear. This study aimed to compare pretreatment inflammatory biomarkers, identify the most informative prognostic indicator, and develop a practical risk-stratification model for LACC. In this multicenter retrospective study, 290 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIB-IIIC cervical squamous cell carcinoma treated with definitive platinum-based CCRT followed by brachytherapy at two tertiary centers were analyzed. Twelve pretreatment inflammatory and nutritional indices, including the hemoglobin-albumin-lymphocyte-platelet (HALP) score, pan-immune-inflammation value (PIV), and neutrophil-to-lymphocyte ratio (NLR), were evaluated for overall survival (OS) and progression-free survival (PFS) using the concordance index (C-index), time-dependent area under the curve (AUC), and Brier score. Cox regression identified independent prognostic factors, and HALP-based nomograms were internally validated. Among all biomarkers, HALP showed the best and most stable prognostic performance for both OS and PFS, with the highest discrimination and lowest prediction error. Low HALP remained independently associated with worse OS and PFS in multivariable analysis (OS: hazard ratio [HR], 1.654; 95% confidence interval [CI], 1.165-2.366; PFS: HR, 1.702; 95% CI, 1.233-2.344). Nomograms integrating HALP, tumor size, and human papillomavirus (HPV) status showed good calibration and improved predictive accuracy beyond FIGO stage and the baseline clinical model. HALP may therefore serve as a robust, inexpensive, and clinically accessible biomarker for individualized risk stratification in LACC.

Objective: To compare the therapeutic effects of hemithyroidectomy (HT) versus total thyroidectomy (TT) on sporadic medullary thyroid carcinoma (sMTC). Methods: Clinical data of sMTC patients firstly treated in Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2019 were reviewed retrospectively. The patients were categorized into the HT group and the TT group based on the extents of primary tumor resection. The differences in clinical characteristics between the two groups were compared. A 1∶1 matching of variables including tumor stage and mulifocality was performed using propensity score matching (PSM) to balance the baseline differences between the two groups. Subsequently, the differences in biochemical cure rate, biochemical recurrence rate, and structural recurrence rate between the two groups were compared. Survival curves were plotted using the Kaplan-Meier method, and the log-rank test was utilized to compare the differences in progression-free survival and overall survival between the two groups. Results: A total of 199 patients with sMTC were included in the study, comprising 80 males and 119 females, with the age [M(Q1,Q3)] of 51.0 (42.0,59.0) years. Before PSM, 117 patients were in HT group and 82 patients were in TT group. There were statistically significant differences in preoperative calcitonin, N stage, TNM stage, and the number of lesions between the two groups (all P<0.05). After PSM, 63 patients were in HT group and 63 patients were in TT group. There was no statistically significant difference in all clinicopathological characteristics between the two groups (all P>0.05). Before PSM, the biochemical cure rate in the HT group was higher than that in the TT group [76.4% (81/106) vs 60.5% (46/76), P=0.021]. There were no statistically significant differences in the biochemical recurrence rate and structural recurrence rate between the HT group and the TT group [4.7% (5/106) vs 7.9% (6/76), 8.5% (10/117) vs 15.9% (13/82), both P>0.05]. The progression-free survival of the HT group was longer than that of the TT group [(137.26±3.53) vs (114.12±5.98) months, P=0.025]. There was no statistically significant difference in overall survival between the HT group and the TT group [(142.12±2.91) vs (126.92±5.15) months, P=0.140]. After PSM, there were no statistically significant differences between the HT group and the TT group in terms of biochemical cure rate [66.7% (40/60) vs 77.2% (44/57)], biochemical recurrence rate [5.0% (3/60) vs 7.0% (4/57)], structural recurrence rate [12.7% (8/63) vs 17.5% (11/63)], progression-free survival [(130.69±5.07) vs (112.19±6.91) months], and overall survival [(136.05±4.04) vs (124.71±6.83) months] (all P>0.05). Conclusions: The therapeutic effects of HT and TT on sMTC are comparable. With careful preoperative evaluation, selective performance of HT is safe and feasible.

Prognostic value of inflammation-based scores in patients with R/R LBCL treated with CD3×CD20 bispecific T-cell engagers.

Introduction: Cemiplimab is a programmed cell death-1 (PD-1) inhibitor approved in patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or radiation. Despite high prevalence of CSCC, immunocompromised or immunosuppressed (IC/IS) patients have been excluded from registration studies due to potentially reduced treatment efficacy. Here, we present the safety and effectiveness of cemiplimab in IC/IS patients with advanced CSCC from a non-interventional study in the real-world setting, at 2 years’ follow-up. Methods: CASE is a phase 4, multicenter, prospective, non-interventional study evaluating the effectiveness and safety of cemiplimab in patients with advanced CSCC (NCT03836105). Data were collected from 65 United States academic and community oncology centers. Results: As of 24 March 2025, 254 patients with advanced CSCC had received ≥1 dose of intravenous cemiplimab 350 mg every 3 weeks. Of these, 42 (16.5%) patients were IC/IS. Most IC/IS patients were white (90.5%), male (76.2%), ≥65 years of age (88.1%), and had locally advanced disease (57.1%). The IC/IS patients were divided into 3 categories: with hematologic malignancies (45% - chronic lymphocytic leukemia, myeloproliferative disorders, or other leukemia), immunosuppressed (33% - immune disorders or human immunodeficiency virus infection), and organ transplant recipients (22% - kidney, liver, or pancreas). Median duration of exposure was 43.9 weeks. Objective response rate was achieved in 45.2% of patients, with 23.8% having a complete response. Median progression-free survival was similar in IC/IS vs non-IC/IS patients, at 14.6 and 15.7 months, respectively. Treatment-related immune-related adverse events occurred in 31.0% of patients and treatment-related serious adverse events occurred in 7.1% of patients. The proportion of IC/IS patients experiencing adverse events was similar to that of the non-IC/IS population. Among the 9 transplant patients, 7 had stable transplant status and 2 had rejection episodes leading to treatment-related allograft loss. Conclusion: This analysis suggests that the safety and efficacy of cemiplimab in IC/IS patients with advanced CSCC are similar to those observed in non-IC/IS patients in this real-world study. Funding: Regeneron Pharmaceuticals, Inc.

Dynamic changes in spleen volume (SpV) may reflect immune and hemodynamic alterations in hepatocellular carcinoma (HCC). This study aimed to evaluate the prognostic significance of SpV dynamics in patients with unresectable HCC (uHCC) treated with tislelizumab plus lenvatinib. We retrospectively analyzed 103 patients with uHCC treated with tislelizumab plus lenvatinib between June 2021 and June 2025. SpV was measured on contrast-enhanced CT at baseline and approximately 3months post-treatment using AI-assisted segmentation with manual correction. The absolute SpV change (ΔSpV) and monthly SpV change rate were calculated. The optimal cut-off values were identified via maximally selected rank statistics. Survival outcomes were assessed using Kaplan-Meier analysis and Cox regression models. Post-treatment SpV increase was observed in 65% of patients and was associated with shorter progression-free survival (PFS). Both ΔSpV and SpV change rate were independent predictors of PFS (HR for ΔSpV: 1.005, P = 0.01; HR for change rate: 1.02, P < 0.00). Cut-off values of 23.81cm3 (ΔSpV) and 8.24cm3/month (change rate) significantly stratified patients into distinct PFS risk groups (11.6 vs. 25.5months, both P < 0.05). Three-month landmark analysis revealed that a SpV change rate ≥ 8.24cm3/month predicted significantly shorter PFS within the first 3months (P = 0.039), while a ΔSpV ≥ 23.81cm3 was associated with significantly poorer PFS after 3months of treatment (P = 0.040). Baseline portal hypertension and larger tumor size correlated with greater SpV increases. SpV dynamics provide a noninvasive imaging biomarker for identifying uHCC patients at elevated risk of progression during tislelizumab plus lenvatinib therapy. Incorporating these volumetric metrics into routine imaging may enhance prognostic assessment and guide risk-adapted patient management.

This retrospective study aimed to compare the efficacy and safety of conventional lipiodol-based transarterial chemoembolization (TACE) combined with prophylactic right inferior phrenic artery (RIPA) embolization versus TACE alone for hepatocellular carcinoma (HCC) located in liver segments VII and VIII. After propensity score matching of 161 eligible patients, 52 received TACE alone (Group A) and 52 received TACE plus prophylactic RIPA embolization (Group B). Primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), time to progression (TTP), tumor response, and adverse events (AEs). The combination therapy significantly improved survival outcomes. Median OS was 32.3 vs. 28.3 months, median PFS was 18.8 vs. 16.5 months, and median TTP was 19.3 vs. 17.5 months. Multivariable Cox analysis confirmed prophylactic RIPA embolization as an independent favorable prognostic factor for OS (HR 0.511, P=0.008), PFS (HR 0.528, P=0.003), and TTP (HR 0.502, P=0.002). Other independent factors included tumor number >3 and Child-Pugh class. The 1-month objective response rate showed no significant difference (67.3% vs. 55.8%, P=0.277). Regarding safety, the overall AE rate was similar between groups (44.2% vs. 42.3%). Complications specifically associated with RIPA embolization in Group B included shoulder pain (19.2%) and hiccups (13.5%), which were mild and self-limited. The incidence of major complications (SIR class C-F) was not significantly different (7.7% vs. 3.8%, P=0.678). One patient in Group B developed a grade 4 liver abscess. For HCC in segments VII/VIII, adding prophylactic RIPA embolization to conventional lipiodol-based TACE provides significant survival benefits, establishing it as an independent prognostic factor, without substantially increasing major treatment-related morbidity. This combined approach represents a valuable therapeutic strategy for this specific patient subset.

Gedatolisib potently targets all four class I PI3K isoforms and mTORC1 and mTORC2 to comprehensively block the PI3K/AKT/mTOR pathway and has shown compelling activity in early clinical trials with palbociclib and fulvestrant. This phase III randomized trial (VIKTORIA-1; ClinicalTrials.gov identifier: NCT05501886) evaluated the efficacy of gedatolisib-based therapy, comparing gedatolisib, palbociclib, and fulvestrant (gedatolisib triplet) and gedatolisib plus fulvestrant (gedatolisib doublet) with fulvestrant monotherapy in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HER2-), PIK3CA wild-type (WT) advanced breast cancer. Eligible patients had disease progression during or after CDK4/6 inhibitor and aromatase inhibitor treatment. Comparison of progression-free survival as assessed by blinded independent central review for gedatolisib triplet versus fulvestrant and gedatolisib doublet versus fulvestrant was the primary objective. A total of 392 patients were randomly assigned 1:1:1. The median study follow-up was 10.1 months. The median progression-free survival was 9.3 months in the gedatolisib-triplet group, 2.0 months in the fulvestrant group (hazard ratio [HR] for progression or death, 0.24 [95% CI, 0.17 to 0.35]; P < .001), and 7.4 months in the gedatolisib-doublet group (HR, 0.33 [95% CI, 0.24 to 0.48]; P < .001 v fulvestrant). Grade ≥3 treatment-related adverse events (TRAEs) reported in the gedatolisib-triplet and gedatolisib-doublet groups, respectively, included neutropenia (62.3%, 0.8%), stomatitis (19.2%, 12.3%), rash (4.6%, 5.4%), hyperglycemia (2.3%, 2.3%), and diarrhea (1.5%, 0.8%). Study treatment discontinuation because of TRAEs was reported in 2.3% (triplet) and 3.1% (doublet) of patients. The addition of gedatolisib to fulvestrant, with or without palbociclib, significantly reduced the risk of disease progression or death in patients with hormone receptor-positive/HER2-, PIK3CA WT advanced breast cancer.

Background A combination of local and systemic therapies is used to treat inguinal lymph node metastases post-penile cancer surgery. This multimodal approach may include surgery, chemotherapy, radiotherapy, and immunotherapy. Case summary We describe an 89-year-old male with a history of penile cancer status post resection, who presented with multiple metastases to the left inguinal lymph nodes confirmed by pathological biopsy. The patient was treated with a combination of radiotherapy and Pembrolizumab. Following this combined modality therapy, he experienced symptomatic relief and achieved a progression-free survival exceeding 38 months. Conclusion This case suggests that concurrent radiotherapy plus Pembrolizumab may achieve durable remission in elderly, chemotherapy-intolerant, metastatic PSCC, but verification in more patients is needed.

Objective: To investigate the prognostic stratification value of MLH1 promoter methylation in a mismatch repair deficiency (dMMR)-type endometrioid endometrial carcinoma (EEC). Methods: A total of 338 patients with confirmed diagnosis of dMMR EEC at Third Hospital of Peking University Health Science Center, from July 2005 to June 2023 were analyzed. Based on the promoter methylation, they were classified into a dMMR methylated (dMMR MET) group (177 cases) and a dMMR nonmethylated (dMMR nonMET) group (127 cases). Somatic mutations were analyzed by targeted sequencing (196/425-gene panel), and transcriptomic differences were assessed by RNA sequencing (Master panel). We compared the clinicopathological characteristics, gene mutation/expression profiles, and molecular pathway activities systematically between the two groups. Results: Compared with the dMMR nonMET group, patients of the dMMR MET group were older significantly [(56.89±8.85) vs. (53.76±9.45) years, P=0.003] and had tumor size of larger diameters [(3.39±1.78) vs. (2.71±1.31) cm, P=0.014]. The menopausal proportion (66.9% vs. 48.8%, P=0.002) and the proportion with tumor buddings (47.5% vs. 30.4%, P=0.036) were higher. No significant differences were identified in FIGO stage, histologic grade, depth of myometrial invasion, lymphovascular invasion, or rate of lymph node metastasis (P>0.05). Mutational profiling revealed that the nonMET group had significantly higher mutation frequencies in CHD4, NF1, SMARCA4, and RET (P<0.05). Transcriptomic analysis demonstrated upregulation of immune-related genes (CCL21, CXCL2) in the MET group, and downregulation of epithelial-mesenchymal transition (EMT)-associated genes (SOX2, FOXA1). Both GO and KEGG enrichment analyses of different gene expression in the MET group demonstrated an association with the MAPK pathway. However, Hallmark pathway analysis showed no significant differences in overall pathway activity between the two groups. Survival analysis revealed no significant differences in progression-free survival (P=0.206) or overall survival (P=0.813) between the groups. Conclusions: The methylation status of the MLH1 promoter has limited value in predicting the prognosis of dMMR EEC. Molecular pathways heterogeneity between the methylated and nonmethylated subgroups suggests the necessity of integrate multi-dimensional indicators to optimize stratification strategies, instead of relying on a single epigenetic marker.

Bridging therapy (BT) prior to brexucabtagene autoleucel (brexu-cel) in mantle cell lymphoma (MCL) is supported by limited evidence. Here, we report BT modality and outcome in 176 patients at 15 centres in the United Kingdom. BT was delivered to 90% (158/176), the majority receiving standard chemotherapy +/- radiotherapy (53%) (SD chemo +/- RT) or targeted therapy (TT) alone (23%). Clinicians favoured SD chemo +/- RT in those with Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 1, blastoid disease, bulk >5 cm and elevated lactate dehydrogenase. Overall response rate (ORR) was 46%. Higher ORR was observed with SD chemo +/- RT (58%), particularly R-BAC (64%). Progressive disease despite BT was associated with a lower ORR to brexu-cel (77% vs. 91%, p = 0.03) and a higher risk of ≥grade 3 ICANS (OR 3.43, 95% CI 1.44-8.10, p = 0.01). SD chemo +/- RT was associated with a higher incidence of ≥grade 3 neutropenia (Month 1), ≥grade 3 thrombocytopenia (Month 1, Month 3) and early non-relapse mortality (<90 days, 13% vs. 0%) compared to TT alone. Neither BT modality nor response impacted progression-free or overall survival post-infusion. Review of haematopoietic reserve prior to the selection of BT regimen, rigorous management of delayed cytopenia post-infusion and more effective and tolerable BT should be prioritised.

Thromboembolism (TE) is a major cause of early mortality in cancer. TARGET-TP randomised high-risk patients with lung or gastrointestinal cancers, identified using a d-dimer/fibrinogen model, to enoxaparin or no thromboprophylaxis; low-risk patients were observed. Thromboprophylaxis reduced TE and 6-month mortality. This study reports extended overall survival (OS) and progression-free survival (PFS) to 36 months. Among high-risk patients, thromboprophylaxis improved OS at 6 and 12 months, with convergence thereafter; no PFS differences were observed. Adjustment for on-study TE attenuated the OS effect, consistent with thrombosis-specific risk reduction. These findings describe the duration and extent of survival benefit achievable with biomarker-guided thromboprophylaxis and highlight that TARGET-TP is the first trial to demonstrate a survival advantage, likely driven by cohort enrichment for thrombotic risk. The improved risk-benefit profile supports real-world evaluation of d-dimer/fibrinogen-guided thromboprophylaxis in lung and gastrointestinal cancers, with validation of the model warranted in additional tumour groups.

Triple-negative breast cancer (TNBC) patients with brain metastases have a poor prognosis and limited treatment options. Preclinical and clinical evidence suggests that radiotherapy may act synergistically with immune checkpoint inhibitors. We conducted an open-label, single-arm, phase II study of atezolizumab plus stereotactic radiosurgery (SRS) in metastatic TNBC patients with brain metastases. The primary endpoint was progression-free survival (PFS) according to the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) bi-compartmental model. Secondary endpoints included extracranial objective response rate, overall survival (OS), and safety and tolerability. A safety run-in analysis for dose-limiting toxicity (DLT) was performed after the first 6 patients were enrolled and completed the assessment period. Six patients were enrolled into the safety run-in phase between May 11, 2018 and October 24, 2019. No DLTs were observed, but the study was closed early due to slow accrual. Patients received a median of 2 atezolizumab cycles (range: 2-16), and SRS was administered to all 6 patients. Treatment-related adverse events (TRAEs) occurred in 4 participants (66.7%); all events were grade 2. The median bi-compartmental PFS was 1.3months (95% confidence interval (CI): 0.95 - NA) and the median OS was 9.7months (95% CI: 3.6 - NA). The best observed response by RECIST 1.1 criteria was stable disease ≥ 24weeks in one participant (16.7%). Concurrent SRS with atezolizumab was feasible in TNBC patients with brain metastases. However, disease outcomes were poor, and the development of effective therapies for these patients remains a significant unmet medical need. https://www. gov NCT03483012. Trial Open to Accrual: 05/01/2018.

The efficacy of combination therapy versus monotherapy in patients with glioblastoma with abnormal epidermal growth factor receptor (EGFR) genes, a systematic review and network meta-analysis.

The guidelines recommend kidney-sparing surgery as the primary treatment for selected patients with low-risk upper urinary tract urothelial carcinoma (UTUC). An important issue with ureteroscopic laser ablation (ULA) is the high rate of surgical-site recurrence, largely attributable to residual lesions at the initial ULA. This trial aimed to investigate the efficacy and safety of oral 5-aminolevulinic acid hydrochloride-mediated photodynamic diagnosis (ALA-PDD)-assisted ULA for UTUC. The study evaluated 20 patients with cTa-1N0M0 UTUC who underwent ALA-PDD-assisted ULA using thulium-holmium:YAG dual lasers. The primary endpoint was the 2-year progression-free survival rate. Treatment-related adverse events (AEs), usefulness of the UroVysion test combined with conventional urinary cytology for detecting recurrent tumors, and longitudinal changes in patient-reported health-related quality of life (HRQoL) after ULA were evaluated. Of the 20 patients, 3 (15 %) experienced disease progression, and the 2-year progression-free survival rate was 82 % (95 % confidence interval [CI], 54-93 %). The lower limit of the 95 % CI for the 2-year PFS rate was less than the prespecified threshold survival rate of 58 %. The most common AEs were transient urinary-related symptoms. No grade ≥3 AEs were observed throughout the trial. Due to the low positivity rate of pretreatment UroVysion testing, the study could not evaluate its usefulness for monitoring post-ULA recurrence. Most domains and scales of HRQoL showed acceptable changes during treatment and follow-up evaluation. In particular, the intervention positively affected mental and emotional conditions. This study provided evidence for the potential benefits and efficacy of this treatment option for selected patients with UTUC.

Background Metastatic castration-resistant prostate cancer (mCRPC) remains a clinically aggressive and lethal disease. Circulating tumor DNA (ctDNA), as a minimally invasive biomarker, has shown prognostic utility in several solid tumors. However, its clinical relevance in mCRPC has not been comprehensively elucidated. Methods A systematic search of PubMed and EMBASE was conducted from inception to July 2025 to identify studies evaluating the prognostic impact of baseline ctDNA levels in patients with mCRPC. Eligible studies reported associations between ctDNA levels and survival outcomes. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for overall survival (OS), progression-free survival (PFS), radiographic PFS (rPFS), and prostate specific antigen PFS (PSA-PFS) using random-effects models. Results Twenty-four studies encompassing 5,272 patients met the inclusion criteria. Elevated baseline ctDNA levels were significantly associated with inferior OS (HR: 3.45; 95% CI: 2.77–4.31), PFS (HR: 2.26; 95% CI: 1.74–2.93), rPFS (HR: 2.39; 95% CI: 1.85–3.10), and PSA-PFS (HR: 2.50; 95% CI: 1.81–3.46). Subgroup analyses showed that the negative prognostic impact of high baseline ctDNA levels on OS remained consistent regardless of detection methods, treatment types, and stratification strategies. Conclusion High baseline ctDNA levels—regardless of measurement approach or therapeutic context—are associated with markedly worse clinical outcomes in mCRPC. These findings highlight ctDNA as a clinically meaningful, noninvasive prognostic biomarker, supporting its integration into personalized risk stratification frameworks and therapeutic decision-making in mCRPC. Systematic Review Registration https://www.crd.york.ac.uk/prospero/ , identifier CRD420251108650.

For patients with left-sided metastatic colorectal cancer (mCRC), the recommended first-line treatment is anti-epidermal growth factor receptor (anti-EGFR) antibodies, such as cetuximab or panitumumab, plus doublet chemotherapy. However, the differences in outcomes between cetuximab and panitumumab remain unknown. Clinical data of patients with left-sided all RAS or KRAS wild-type mCRC who received cetuximab or panitumumab plus doublet chemotherapy were retrospectively collected from 24 institutions in Japan. The patients were divided into two groups: the cetuximab and panitumumab groups. Overall survival (OS), progression-free survival (PFS), and response rate (RR) were compared between the two groups. A total of 233 patients were enrolled: 87 (37.3%) in the cetuximab group and 146 (62.7%) in the panitumumab group. Median OS, PFS, and RR of the cetuximab and panitumumab groups were 26.6months (95% confidence interval [CI], 19.7-33.4) versus 31.8months (95% CI, 25.7-37.9), 9.7months (95% CI, 6.9-12.5) versus 12.4months (11.1-13.7), and 57.8% versus 71.0%, respectively. In multivariate analysis, OS and RR were significantly better in the panitumumab group than in the cetuximab group (adjusted hazard ratio 0.69, 95% CI 0.50-0.99, p = 0.04; adjusted odds ratio 2.00, 95% CI 1.07-3.73, p = 0.03) and PFS was similar between the two groups (adjusted hazard ratio 0.75, 95% CI 0.55-1.01, p = 0.05). As a first-line treatment for patients with left-sided all RAS or KRAS wild-type mCRC, panitumumab plus doublet chemotherapy may be suggested better efficacy outcomes than cetuximab plus doublet chemotherapy.

Introduction Trastuzumab combined with pertuzumab (HP) is a first-line therapy for advanced breast cancer (ABC). However, trastuzumab combined with pyrotinib (HPyr) could also exert complementary and synergistic effects. Currently, clinical trials directly comparing the effectiveness of the above two treatment approaches are lacking. Herein, a registered single-center, retrospective study (NCT04609540) was caried out. Methods In the present study, patients diagnosed with human epidermal growth factor receptor 2 (HER2)-positive ABC and treated with dual-target first-line rescue treatment at the Shandong Cancer Hospital between January 2018 and February 2023 were included. Patients were assigned to the HP or HPyr treatment groups by the physician-in-charge. The clinical, pathological and prognostic data of all patients were collected and recorded. Results Among the 89 patients included, 47 received HP, while the remaining 42 HPyr. The therapeutic effect of each treatment approach was determined via evaluating progression-free survival (PFS). The results showed that patients who were treated with HPyr displayed a higher progression rate (71.4% vs. 63.8%) compared with those treated with HP. However, statistical significance was not reached (mean PFS, 21.0±1.9 vs. 24.1±2.8 months; P=0.653). In addition, patients of &amp;gt;60 years old, who received HPyr and younger patients (≤40 years old) who received HP had longer PFS (22.8±4.9 vs. 16.8±4.2 months; P=0.332; and 27.4±5.5 vs. 15.8±5.6 months; P=0.098, respectively). PFS without significant differences was also obtained in the other subgroups. Furthermore, HP showed better clinical efficacy in young patients compared with older ones, while HPyr benefitted older patients. In the other subgroups, the two dual-target regimens also displayed curative effects, without significant differences. Discussion Overall, the results of the current study suggested that HPyr could be equivalently used as HP, as a first-line treatment strategy for patients with HER2-positive ABC. Currently, more prospective large-sample studies are needed to further validate our conclusions.

Brain metastases (BMs) of triple-negative breast cancer (TNBC) are lethal, often associated with a limited life span and lack of effective antitumor agents. Here we reported a triple combination therapy consisting of adebrelimab, bevacizumab, and cisplatin/carboplatin in BMs of TNBC. This phase II clinical trial involved patients with TNBC with active BMs. Participants were administered with adebrelimab, bevacizumab, and cisplatin/carboplatin until disease progression or unacceptable toxic effects. The primary end point was the objective response rate in CNS (CNS-ORR) according to the Response Assessment in Neuro-Oncology BMs criteria, and the secondary end points included the clinical benefit rate in CNS (CNS-CBR), progression-free survival (PFS), overall survival (OS), the first progression site, and safety. A total of 35 patients were enrolled and treated, and the median lines of previous treatment were 2 (range, 0-4). The confirmed CNS-ORR was 77.1% (27/35, 95% CI, 59.9 to 89.6), and the CNS-CBR was 80.0% (28/35, 95% CI, 63.1 to 91.6). The median overall PFS was 8.3 months (95% CI, 5.8 to 11.5), whereas the median CNS-PFS was 10.3 months (95% CI, 7.4 to 14.3) and the median OS was 21.1 months (95% CI, 13.2 to not reached). Among the 28 patients who progressed, progression was intracranial-only in 32.1% (9/28) patients, extracranial-only in 35.7% (10/28) patients, and both in 32.1% (9/28) patients. The incidence of grade ≥3 treatment-related adverse events was 65.7% (23/35). Treatment-related serious adverse events occurred in five patients (14.3%), and no treatment-related deaths were reported. The combination of adebrelimab, bevacizumab, and cisplatin/carboplatin was the first regimen to demonstrate promising intracranial antitumor activity and prolonged PFS and CNS-PFS, along with a manageable safety profile, warranting further investigation.

The ability of IL12 to stimulate production of IFNγ suggested it might improve the efficacy of low-dose IFNα. In this phase II trial, patients with metastatic malignant melanoma were administered recombinant human (rh) IL12 followed by IFNα2b. Primary endpoints were clinical response and progression-free survival. Secondary objectives were to evaluate the effect of endogenous IFNγ on JAK-STAT signaling and IFN-regulated genes in peripheral blood mononuclear cells (PBMC). Patients with advanced melanoma received rhIL12 on day 1 and IFNα2b on days 2 to 6 of a 14-day cycle. rhIL12 was given intravenously at 300 ng/kg. IFNα2b was dosed at 3 × 106 units subcutaneously. Plasma IFNγ was assayed by ELISA; JAK-STAT signaling was measured in PBMCs by flow cytometry. The proportion of responders was assessed via Simon two-stage design. Thirty-eight patients were enrolled. The regimen was well-tolerated. Two patients achieved a partial response lasting 6 months or longer (5.3%). IL12 administration led to an increase in mean plasma IFNγ from 33.57 pg/mL at baseline to a maximum of 564.86 pg/mL and increased expression of STAT1 and STAT2 in PBMCs. Generation of phosphorylated STAT1 and IFN-simulated gene product 15 in response to IFNα was enhanced following IL12. rhIL12 given prior to IFNα2b stimulated production of IFNγ, which led to increased levels of JAK-STAT signaling intermediates in patient PBMCs. Combination therapy was reasonably well-tolerated but conferred marginal benefit in patients with metastatic melanoma. These results can inform future studies that use recombinant IL12 or novel IL12 constructs.

Chidamide is an oral subtype-selective histone deacetylase inhibitor that has been used as an anti-cancer agent. This study evaluated the efficacy and safety of chidamide plus fulvestrant in the treatment of HR-positive and HER2-negative advanced breast cancer. Eligible patients were women between the ages of 18-75 with HR + /HER2- advanced invasive breast cancer, whose disease relapsed or progressed after endocrine therapy with or without a CDK4/6 inhibitor (CDK4/6i). Eligible patients were treated with oral chidamide (30mg twice weekly) plus intramuscular fulvestrant (500mg on days 1 and 15 of cycle one, and then on day one of each subsequent 28day cycle) until disease progression or toxicity related intolerance. Premenopausal women received a concomitant GnRH analogue. The primary endpoint was progression-free survival. Between Mar 19, 2021, and Mar 20, 2024, a total of 33 patients were enrolled. Of these, 30 patients who completed at least one post-baseline tumor assessment were included in the efficacy analysis. The median age was 54.5years (range 31-70), with all 30 (100%) patients having an Eastern Cooperative Oncology Group Performance Status of 1. Visceral metastases were present in 80% (n = 24) of cases, and 50% (n = 15) exhibited metastases in > 3 anatomical sites. The median number of prior treatments was 2 (range 1-4). In total, 40% (n = 12) had undergone prior CDK4/6i therapy. The median progression-free survival for the entire cohort was 6.3months (95% CI 5.0-9.0). The objective response rate (ORR) was 10%, with a disease control rate (DCR) of 83.3% (partial response + stable disease) and a clinical benefit rate (CBR) of 23.3%. Treatment related adverse events of any grade occurred in 30 (100%) patients, of those 9 (30%) were ≥ grade 3. The most frequent hematologic toxicities included leukopenia (all-grade: 67%; grade 3-4: 19%), followed by neutropenia (all-grade: 47%; grade 3-4: 19%) and thrombocytopenia (all-grade: 40%; grade 3-4: 6%). No treatment-related deaths occurred. Chidamide combined with fulvestrant showed encouraging antitumor activity and tolerable toxicity in pts with HR + /HER2- advanced breast cancer that had progressed after previous endocrine therapy. Trial registration ChiCTR2100044282, registered on March 14th 2021.