Scirrhous gastric cancer (SGC), including the Borrmann type IV subtype, is characterized by a desmoplastic stroma, rapid progression, and a poor prognosis with limited effective treatment options. While fibroblast growth factor receptor 2 (FGFR2) alterations are recognized therapeutic targets in some cancers, their clinical application in gastric cancer, particularly in SGC, remains underexplored. We present the case of a 47-year-old female with advanced, chemotherapy-refractory Borrmann type IV gastric cancer harboring FGFR2 rearrangement and amplification. Treatment with the selective FGFR1-3 inhibitor pemigatinib elicited a marked clinical and serological response; however, disease progression ensued after 3 months. Comprehensive genomic profiling revealed an acquired FGFR2 N549K mutation, a recognized on-target resistance mechanism. Subsequent administration of the irreversible FGFR1-4 inhibitor futibatinib was associated with a declining trend in tumor biomarkers, indicating preliminary antitumor activity against the resistant clone. This case underscores the clinical activity of FGFR inhibition in FGFR2-altered SGC and exemplifies the emergence of kinase domain mutations as a principal resistance pathway. It further suggests that irreversible FGFR inhibitors may represent a rational therapeutic strategy upon progression on prior FGFR-directed therapy, warranting further clinical investigation in this molecularly defined patient subset.

Tertiary lymphoid structures (TLS) are associated with favorable outcomes in non-small cell lung cancer (NSCLC) following neoadjuvant immunochemotherapy. However, the biological and prognostic differences between TLS in peritumoral inflammation (PI) and the tumor bed (TB) remain unclear. We analyzed 254 patients with NSCLC from three centers: 98 treated with neoadjuvant immunochemotherapy (NICT), 54 treated with neoadjuvant chemotherapy (NCT), and 102 treatment-naïve patients. PI and TB TLS abundance and maturation were assessed in relation to pathological response and survival. Exploratory spatial transcriptomics characterized their cellular composition and intercellular communication. PI was more prevalent in the NICT cohort (77.5

Neoadjuvant-targeted treatment (NTT) has advanced significantly in patients with mutant non-small cell lung cancer (NSCLC) undergoing surgery; however, its favourable duration remains unclear. This real-world study explored the association between NTT duration and therapeutic outcomes. This study retrospectively enrolled multicentre patients with mutant NSCLC who received ≥ 2 NTT cycles followed by complete surgical resection. Correlations among treatment duration, therapeutic responses, and safety were analysed using major pathological response (MPR) as the primary endpoint. Univariate and multivariate logistic regression analyses identified the independent predictors of MPR. Among the 54 patients ultimately included, the objective response rate (ORR) and MPR rate in the overall cohort were 48.1

Despite chemo-immunotherapy has been applied to the neoadjuvant treatment of non-small cell lung cancer (NSCLC), the impacts of dosage and the order of medication on treatment efficacy and safety remain largely unexplored. We originally designed an exploratory study to investigate the efficacy and safety of reduced-dose chemotherapy combined with delayed immunotherapy as well as the dynamic changes of circulating tumor DNA (ctDNA) and T cell receptor (TCR) during the therapy.Patients with clinical stage IIA to IIIA resectable NSCLC were treated with 2 cycles of reduced-dose platinum-based chemotherapy on day 1 combined with immunotherapy on day 5. The same postoperative modified adjuvant therapy regimen was administered for 2 cycles. Plasma samples at different time-points were collected and performed with T cell receptor (TCR) and circulating tumor DNA (ctDNA) sequencing.38 patients received modified chemo-immunotherapy. The proportion of patients exhibiting complete response and partial response was 5.3% and 68.4%, respectively. The confirmed objective response rate was 73.7%. Radiological downstaging was achieved in 39.5%. Major pathologic response and complete pathologic response were observed in 47.4% and 31.6% of patients, respectively. Only one patient experienced grade 3 adverse event. Further analyses revealed that this modified chemo-immunotherapy led to the expansion of predominant TCR clones and reduction of tumor burden after the first cycle of chemotherapy.The promising clinical efficacy and low side effects of modified neoadjuvant chemo-immunotherapy position it as a prospective and innovative strategy for NSCLC.

This study aims to assess the therapeutic efficacy and safety of nivolumab combined with chemotherapy as a first-line treatment for advanced or metastatic gastric cancer, specifically comparing the outcomes of oxaliplatin-based versus albumin-bound paclitaxel (nab-paclitaxel)-based therapies. We retrospectively analyzed 93 patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma treated at the First Medical Center of Chinese PLA General Hospital from September 2017 to November 2022. Patients were categorized into the nivolumab + oxaliplatin (N-OX group) or nivolumab + nab-paclitaxel (N-AP group) based on the chemotherapy regimen. Progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety were evaluated as endpoints. At the end of the follow-up period on September 31, 2023, we reported an ORR of 65.6

Background Although left ventricular (LV) dysfunction has been studied in patients with solid tumors and abnormal myocardial enzymes receiving immune checkpoint inhibitors, little is known about the early changes in LV strains and function in patients without significant markers of myocardial injury. Methods A total of 57 patients with solid tumors who received chemotherapy and immune checkpoint inhibitors were enrolled from December 2019 to June 2022. Echocardiography was performed at baseline and after 3 and 6 months. LVD, LVS, Volume D, Volume S, LVEF, Em, Am, E/A, E/e’, heart rate, and GLS were collected by 2 DE. Serum biomarkers of myocardial injury were tested at baseline and after 3 and 6 months. The discrimination of echocardiographic parameters and biomarkers between groups was statistically analyzed using SPSS version 19.0 software. Results A total of 49 patients (35 males; mean age ± SD, 57.5 ± 9.89 years) were included in this study. No significant differences were found in conventional ultrasound parameters, or HR throughout the follow-up period. The LA area decreased from 16.44 ± 4.17 at baseline to 15.13 ± 4.01 at 6-month follow-up (p < 0.001). Compared to baseline, the GLSs at the 3-month follow-up and 6-month follow-up were significantly reduced (p < 0.05). The creatine kinase and CK-MB levels showed an upward trend (p < 0.05). The levels of lactate dehydrogenase isoenzyme (p < 0.05) decreased at 3 months and increased at 6 months. E/e’ was negatively correlated with troponin T, creatine kinase, and blood glucose levels (r=-0.477, -0.258, -0.426, respectively; p < 0.05). GLS (3P) levels were positively correlated with creatine kinase (r = 0.017, p < 0.05). Patients were divided into two groups based on the presence (G1,15 cases) of other system immune responses or absence (G0, 34 cases) of other system immune responses. There were statistical differences in EF values among different time points (p < 0.05). There was no statistically significant difference in left ventricular strain parameters between the G0 and G1 groups (p > 0.05), but significant differences were observed at different time points (p < 0.05). Conclusions The evaluation of left ventricular strain parameters by echocardiography is of great significance for early detection of myocardial toxicity caused by immunotherapy without evidence of elevated myocardial enzymes. Trial registration : retrospectively registered

Background Immunotherapy targeting PD-1/PD-L1 has revolutionized the treatment of extensive-stage small cell lung cancer (ES-SCLC). However, clinical trials suggest differential efficacy of anti-PD-1 agents and anti-PD-L1 agents in first-line treatment of ES-SCLC. This retrospective multicenter study aimed to compare the efficacy and safety of anti-PD-1 agents versus anti-PD-L1 agents in first-line treatment of ES-SCLC in real-world practice. Methods Patients with pathologically or cytologically confirmed ES-SCLC treated with platinum plus etoposide combined with anti-PD-1 or PD-L1 agents as first-line treatment in different centers of PLA General Hospital between January 2017 and October 2021 were included for this study. Survival outcomes and safety were compared between patients receiving anti-PD-1 and PD-L1 agents. Results Of the total 154 included patients, 68 received anti-PD-1 agents plus chemotherapy (PD-1 group), and 86 received anti-PD-L1 agents plus chemotherapy (PD-L1 group). Progression-free survival (PFS) and overall survival (OS) in the entire cohort were 7.6 months (95% confidence interval [CI]: 6.5–8.2 months) and 17.4 months (95% CI: 15.3–19.3 months), respectively. Median PFS and OS were comparable between the PD-1 group and PD-L1 group (PFS: 7.6 months vs. 8.3 months, HR = 1.13, 95% CI: 0.79–1.62, p = 0.415; OS: 26.9 months vs. 25.6 months, HR = 0.96, 95% CI: 0.63–1.47, p = 0.859. The objective response rate and disease control rate were comparable between the two groups: 79.4% vs. 79.1% and 92.6% vs. 94.2%, respectively. The 6-month, 12-month, and 18-month PFS and OS rates were slightly higher in the PD-L1 group than in the PD-1 group, while the 24-month PFS rate was slightly higher in the PD-1 group than in the PD-L1 group. Stratified analysis showed that locoregional thoracic radiotherapy and normal lactate dehydrogenase level were independent predictors of better OS in ES-SCLC patients treated with first-line chemotherapy plus ICI. Adverse events were not significantly different between the two groups. Conclusions Anti-PD-1 agents and anti-PD-L1 agents combined with chemotherapy as first-line treatment for ES-SCLC are comparably effective and well tolerated.

Background Pancreatic ductal adenocarcinoma (PDAC) is in urgent need of a second‐line or later‐line treatment strategy. We aimed to analyze the efficacy and safety of additional anlotinib, specifically anlotinib in combination with immunotherapy, in patients with PDAC who have failed first‐line therapy. Methods Patients with pathological diagnosis of PDAC were additionally treated with anlotinib, and some patients were treated with anti‐PD‐1 agents at the same time, which could be retrospectively analyzed. The efficacy and safety of additional anlotinib were evaluated. Results A total of 23 patients were included. In patients treated with additional anlotinib, the overall median progression‐free survival (PFS) was 1.8 months and the median overall survival (OS) was 6.3 months, regardless of anti‐PD‐1 agents. Among patients receiving additional anlotinib in combination with anti‐PD‐1 agents, median PFS and OS were 1.8 and 6.5 months, respectively. Adverse events (AEs) were observed in 16 patients (69.6%). In patients treated with additional anlotinib, the majority of AEs were grade 1–3. Univariate analysis revealed that patients with baseline red blood cell distribution width (RDW) <14% treated with additional anlotinib plus anti‐PD‐1 agents had significantly longer OS than patients with baseline RDW ≥14% ( p = 0.025). Patients with additional anlotinib plus anti‐PD‐1 agents as second‐line therapy had a longer OS than those treated as later‐line therapy ( p = 0.012). Multivariate analysis showed that baseline RDW was the only independent risk factor for OS ( p = 0.042). Conclusion The combination of anlotinib and immunotherapy represents an effective add‐on therapy with tolerable AEs as second‐ or later‐line therapy in patients with PDAC, particularly in patients with baseline RDW <14%.

201 Background: Non-small cell lung cancer (NSCLC) is a leading cause of brain metastases. Advances in gene-directed therapies have shifted the focus away from traditional platinum-based chemotherapies. Key targeted mutations in NSCLC include EGFR, ALK, BRAF, MET exon skipping, RET fusions, and ROS1 rearrangements. This retrospective study aims to explore overall survival (OS) and progression-free survival (PFS) in NSCLC BM patients with these gene mutations. Methods: In this retrospective study, conducted by the Department of Medical Oncology at Beijing Tiantan Hospital and the First Medical Center, PLA General Hospital, we reviewed 1526 patients with NSCLC brain metastasis from 2010 to 2022. Data collected included molecular marker status, systemic therapies, and dates of progression. The analysis focused on determining OS and PFS from the time of brain metastasis diagnosis to the last follow-up or death. Statistical analysis used the Cox proportional hazards model. Results: The study reviewed 1526 patients, identifying the following mutation distribution: EGFR mutations in 628 patients, ALK rearrangements in 207 patients, ROS1 rearrangements in 64 patients, BRAF mutations in 31 patients, MET exon skipping in 55 patients, and RET fusions in 42 patients. Significant variations in median OS (mOS) and median PFS (mPFS) were observed across these mutation groups. Patients with EGFR and ALK mutations demonstrated longer mOS and mPFS. Patients with RET and ROS1 mutations also showed better outcomes compared to those with BRAF and MET mutations. Conclusions: This study highlights the importance of molecular mutations in NSCLC BM as prognostic indicators and therapeutic targets. EGFR and ALK mutations were associated with more favorable outcomes, emphasizing the need for personalized medicine in managing NSCLC BM. The study suggests further research focused on specific mutation types is crucial to refine treatment strategies and improve patient care.

Background:With its diverse genetic foundation and heterogeneous nature, non-small cell lung cancer (NSCLC) needs a better comprehension of prognostic evaluation and efficient treatment targeting.Methods:Bioinformatics analysis was performed of The Cancer Genome Atlas (TCGA)-NSCLC and GSE68571 dataset. Overlapping differentially expressed genes (DEGs) were used for functional enrichment analysis and constructing the protein-protein interaction (PPI) network. In addition, key prognostic genes were identified through prognostic risk models, and their expression levels were verified. The phenotypic effects of cell division cycle 25C (CDC25C) regulation on NSCLC cell lines were assessed by in vitro experiments using various techniques such as flow cytometry, Transwell, and colony formation. Protein levels related to autophagy and apoptosis were assessed, specifically examining the impact of autophagy inhibition [3-methyladenine (3-MA)] and the miR-142-3p/CDC25C axis on this regulatory system.Results:CDC25C was identified as a key prognostic marker in NSCLC, showing high expression in tumor samples. In vitro experiments showed that CDC25C knockdown markedly reduced the capacity of cells to proliferate, migrate, invade, trigger apoptosis, and initiate cell cycle arrest. CDC25C and miR-142-3p displayed a reciprocal regulatory relationship. CDC25C reversed the inhibitory impacts of miR-142-3p on NSCLC cell cycle proliferation and progression. The synergy of miR-142-3p inhibition, CDC25C silencing, and 3-MA treatment was shown to regulate NSCLC cell processes including proliferation, apoptosis, and autophagy.Conclusions:MiR-142-3p emerged as a key player in governing autophagy and apoptosis by directly targeting CDC25C expression. This emphasizes the pivotal role of the miR-142-3p/CDC25C axis as a critical regulatory pathway in NSCLC.

AbstractBackgroundPatients with programmed cell death‐ligand 1 (PD‐L1) ≥50% metastatic non‐small cell lung cancer (NSCLC) treated with first‐line immunotherapy showed heterogeneous tumor responses. In this study, we investigated the clinical and immune‐inflammatory markers distinguishing patients with metastatic NSCLC achieving high depth of tumor response (HDPR) from those with non‐high depth of response (NHDPR). The impact of clinical features on the prognosis of patients with PD‐L1 ≥50% were further clarified.MethodsThe clinical characteristics and immune‐inflammatory markers of 17 patients with PD‐L1 ≥50% metastatic NSCLC at Beijing Tiantan Hospital between July 2020 and December 2023 were retrospectively analyzed.ResultsAmong the 17 patients, seven (41.2%) patients achieved HDPR (range: −50%, −72%) and 10 (58.8%) patients achieved NHDPR (range: −13%, −45%). Below normal CD4 + T lymphocytes/CD8 + T lymphocytes (CD4/CD8) ratio (p = 0.01) and oncogenes and/or tumor suppressor gene mutations (TP53/KRAS/EGFR) (p = 0.001) were found enriched for NHDPR compared with HDPR. With a median follow‐up of 26.0 months (range: 17.2–34.8 months), the median progression‐free survival (PFS) following first‐line immunotherapy and overall survival (OS) were 9.0 months (95% CI: 5.0–13.0) and not reached (NR), respectively. The neutrophil‐to‐lymphocyte ratio (NLR) was identified as an independent prognostic factor on first‐line PFS. Patients with an NLR ≥4 exhibited a shorter median PFS (7.0 months vs. NR; p = 0.033; 95% CI: 1.2–80.2) than those with an NLR <4 following first‐line immunotherapy.ConclusionsAmong patients with PD‐L1 ≥50% metastatic NSCLC who received first‐line immunotherapy, a lower CD4/CD8 ratio and the presence of genes mutations showed a diminished tumor response and a higher NLR ratio exhibited a worse median PFS.

AbstractBackgroundThe absence of thyroid transcription factor 1 (TTF‐1) is associated with a lower frequency of epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma (LUAD). The aim of this study was to assess the impact of TTF‐1 expression on the clinical response to EGFR‐tyrosine kinase inhibitor (TKI) treatment in patients with advanced LUAD.MethodsThe data of patients with advanced LUAD who were admitted to the Beijing Tiantan Hospital and Peking University Cancer Hospital (China) between April 2009 and May 2023 was retrospectively analyzed.ResultsA total of 227 patients diagnosed with advanced LUAD were included, of which 28.2% (64/227) had TTF‐1‐negative adenocarcinoma, while 54.6% (124/227) harbored EGFR mutations. Negative TTF‐1 expression significantly correlated with male sex (68.8% vs. 42.3%, p < 0.001), history of heavy smoking (57.8% vs. 36.2%, p = 0.003), poorly differentiated tumors (86.5% vs. 43.2%, p < 0.001), and lower frequency of EGFR mutations (26.6% vs. 65.6%, p < 0.001) compared with TTF‐1 positivity. Multivariable logistic regression showed that low prevalence of EGFR mutations (p < 0.001) and male sex (p = 0.006) were independent predictive factors for the negative expression of TTF‐1. Patients lacking TTF‐1 also exhibited worse overall response rate (ORR; 23.5% vs. 54.2%, p = 0.019), disease control rate (DCR; 58.8% vs. 89.7%, p = 0.003), and median progression‐free survival (PFS; 2.9 vs. 11.6 months, p < 0.001) following treatment with EGFR‐TKIs compared to the TTF‐1‐positive patients with EGFR mutations.ConclusionsPatients with TTF‐1‐negative and EGFR‐mutant LUAD show a diminished response to EGFR‐TKIs.

Abstract Background The aim of this study was to investigate the efficacy of bevacizumab (Bev) in reducing peritumoral brain edema (PTBE) after stereotactic radiotherapy (SRT) for lung cancer brain metastases. Methods A retrospective analysis was conducted on 44 patients with lung cancer brain metastases (70 lesions) who were admitted to our oncology and Gamma Knife center from January 2020 to May 2022. All patients received intracranial SRT and had PTBE. Based on treatment with Bev, patients were categorized as SRT + Bev and SRT groups. Follow‐up head magnetic resonance imaging was performed to calculate PTBE and tumor volume changes. The edema index (EI) was used to assess the severity of PTBE. Additionally, the extent of tumor reduction and intracranial progression‐free survival (PFS) were compared between the two groups. Results The SRT + Bev group showed a statistically significant difference in EI values before and after radiotherapy (p = 0.0115), with lower values observed after treatment, but there was no difference in the SRT group (p = 0.4008). There was a difference in the distribution of EI grades in the SRT + Bev group (p = 0.0186), with an increased proportion of patients at grades 1–2 after radiotherapy, while there was no difference in the SRT group (p > 0.9999). Both groups demonstrated a significant reduction in tumor volume after radiotherapy (p < 0.05), but there was no difference in tumor volume changes between the two groups (p = 0.4089). There was no difference in intracranial PFS between the two groups (p = 0.1541). Conclusion Bevacizumab significantly reduces the severity of PTBE after radiotherapy for lung cancer. However, its impact on tumor volume reduction and intracranial PFS does not reach statistical significance.

OBJECTIVES:Clear cell renal cell carcinoma (ccRCC) is a highly prevalent subtype of malignant renal tumor, but unfortunately, the survival rate remains unsatisfactory. The aim of the present study is to explore genomic features that are correlated with cancer stage, allowing for the identification of subgroups of ccRCC patients with high risk of unfavorable outcomes and enabling prompt intervention and treatment.METHODS:We compared the gene expression levels across ccRCC patients with diverse cancer stages from The Cancer Genome Atlas (TCGA) database, which revealed characteristic genes associated with tumor stage. We then extracted prognostic genes and used least absolute shrinkage selection operator (LASSO) regression to select four genes for feature extraction and the construction of a prognostic risk model.RESULTS:We have identified a total of 171 differentially expressed genes (DEGs) that are closely linked to the tumor stage of ccRCC through difference analysis. A prognostic risk model constructed based on the expression levels of ZIC2, TFAP2A-AS1, ITPKA, and SLC16A12 holds significant prognostic value in ccRCC. The results of the functional enrichment analysis imply that the DEGs are mainly involved in the regulation of immune-related signaling pathways, and therefore may have a significant function in immune system regulation of ccRCC.CONCLUSIONS:Our study has successfully identified significant DEGs between high- and low-staging groups of ccRCC using bioinformatics methods. The construction of a prognostic risk model based on the expression levels of ZIC2, TFAP2A-AS1, ITPKA, and SLC16A12 has displayed promising prognostic significance, indicating its valuable potential for clinical application.

Background:The aberrant regulation of cell cycle is significantly correlated with cancer carcinogenesis and progression, in which cell cycle checkpoints control phase transitions, cell cycle entry, progression, and exit. However, the integrative role of cell cycle checkpoint-related genes (CRGs) in bladder carcinoma (BC) remains unknown.Methods:The transcriptomic data and clinical features of BC patients were downloaded from The Cancer Genome Atlas (TCGA), used to identify CRGs correlated with overall survival (OS) by univariate Cox regression analysis. Then, the multivariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses further developed a prognostic CRG signature, which was validated in three external datasets retrieved from Gene Expression Omnibus (GEO). The receiver operating characteristic curve (ROC) analysis was conducted for evaluating the performance of the CRG signature in prognosis prediction. RNA sequencing (RNA-Seq) was performed to explore the expression difference in the identified CRGs between tumor and normal tissue samples from 11 BC patients in the local cohort. Ultimately, genomic profiles and tumor microenvironment (TME), and the Genomics of Drug Sensitivity in Cancer (GDSC) were investigated to guide precision treatment for BC patients with different CRG features.Results:The novel constructed 23-CRG prognostic signature could stratify BC patients into high-risk and low-risk groups with significantly different outcomes (median OS: 13.64 vs. 104.65 months). Notably, 19 CRGs were the first to be identified as being associated with BC progression. In three additional validation datasets (GSE13507, GSE31684, and GSE32548), higher CRG scores all indicated inferior survival, demonstrating the robust ability of the CRG signature in prognosis prediction. Moreover, the CRG signature as an independent prognostic factor had a robust and stable risk stratification for BC patients with different histological or clinical features. Then, a CRG signature-based nomogram with a better performance in prognostic prediction [concordance index (C-index): 0.76] was established. Functional enrichment analysis revealed that collagen-containing extracellular matrix (ECM), and ECM-related and MAPK signaling pathways were significantly associated with the signature. Further analysis showed that low-risk patients were characterized by particularly distinctive prevalence of FGFR3 (17.03% vs. 6.67%, p < 0.01) and POLE alterations (7.97% vs. 2.50%, p < 0.05), and enrichment of immune infiltrated cells (including CD8+ T cells, CD4+ naïve T cells, follicular helper T cells, Tregs, and myeloid dendritic cells). RNA-seq data in our local cohort supported the findings in the differentially expressed genes (DEGs) between tumor and normal tissue samples, and the difference in TME between high-risk and low-risk groups. Additionally, CRG signature score plus FGFR3 status divided BC patients into four molecular subtypes, with distinct prognosis, TME, and transcriptomic profiling of immune checkpoint genes. Of note, CRG signature score plus FGFR3 status could successfully distinguish BC patients who have a higher possibility of response to immunotherapy or chemotherapy drugs.Conclusions:The CRG signature is a potent prognostic model for BC patients, and in combination with FGFR3 alterations, it had more practical capacity in the prediction of chemotherapy and immunotherapy response, helping guide clinical decision-making.

Combinatorial systemic chemotherapy is a powerful treatment paradigm against cancer, but it is fraught with problems due to the emergence of chemoresistance and additive systemic toxicity. In addition, coadministration of individual drugs suffers from uncontrollable pharmacokinetics and biodistribution, resulting in suboptimal combination synergy. Toward the goal of addressing these unmet medical issues, we describe a unique strategy to integrate multiple structurally disparate drugs into a self-assembling nanococktail platform. Conjugation of a polyunsaturated fatty acid (e.g., linoleic acid) with two chemotherapies generated prodrug entities that were miscible with tunable drug ratios for aqueous self-assembly. In vitro and in vivo assays were performed to investigate the mechanism of combinatorial nanococktails in mitigating chemoresistance and the efficacy of nanotherapy. The coassembled nanoparticle cocktails were feasibly fabricated and further refined with an amphiphilic matrix to form a systemically injectable and PEGylated nanomedicine with minimal excipients. The drug ratio incorporated into the nanococktails was optimized and carefully examined in lung cancer cells to maximize therapeutic synergy. Mechanistically, subjugated resistance by nanococktail therapy was achieved through the altered cellular uptake pathway and compromised DNA repair via the ATM/Chk2/p53 cascade. In mice harboring cisplatin-resistant lung tumor xenografts, administration of the nanococktail outperformed free drug combinations in terms of antitumor efficacy and drug tolerability. Overall, our study provides a facile and cost-effective approach for the generation of cytotoxic nanoparticles to synergistically treat chemoresistant cancers.

Anti-programmed death-1 (PD-1) therapy has been extensively used to treat cancer. Recently, the combination of immunotherapy and anti-angiogenic therapy has emerged as a novel treatment approach. Therefore, we designed a study to evaluate the real-world benefit of the combination of anti-PD-1 and anti-angiogenesis therapy in patients with non-small cell lung cancer (NSCLC).We obtained the medical records of patients at the Chinese People's Liberation Army General Hospital who received either nivolumab or pembrolizumab combined with anti-angiogenesis therapy from January 2015 to December 2018. The overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated for all patients.Sixty-nine patients with NSCLC were included in our study. The ORR was 31.9% (95% CI: 20.6-43.2%) and the median PFS was 8.37 months (95% CI: 6.5-10.0 months). The subgroup analysis statistically revealed a significant difference in ORR for patients receiving first-line treatment vs other lines, and the values were 58.8% (95% CI: 32.7-84.9%) compared with 23.1% (95% CI: 11.2-34.9%). We also observed a significant improvement in PFS, with a median value of 10.5 months (95% CI: 7.4-13.1 months) for patients without EGFR mutations and 5.4 months (95% CI: 4.0-6.3 months) for patients with EGFR mutations.The real-world ORR, PFS, and OS were comparable to previous clinical trials, despite the patients' different baseline characteristics. Importantly, compared with patients having identified EGFR mutations, patients without EGFR mutations had a better PFS. Furthermore, these data support the use of anti-PD-1 combined with anti-angiogenesis therapy as a novel treatment approach for patients with NSCLC.

Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII) have been identified as predictors of treatment response in a variety of cancers. We conducted a retrospective analysis to investigate the usefulness of NLR, PLR and SII at baseline and at 6 weeks post-treatment as predictors of response to anti-PD-1/PD-L1 antibody treatment in small cell lung cancer (SCLC). Data of 41 SCLC patients receiving immunotherapy as second- or later-line treatment were analyzed. The overall median progression-free survival (PFS) was 5.1 months (95% CI 3.2–6.2). The median PFS was significantly longer in patients with NLR < 5 than in patients with NLR ≥ 5 at 6 weeks post treatment (HR = 0.29, 95%CI 0.09–0.96, P = 0.04). However, median PFS was comparable between patients with NLR < 5 and patients with NLR ≥ 5 at baseline (HR = 0.75, 95% CI 0.24–2.26, P = 0.56). The median PFS was similar between patients with PLR < 169 and those with PLR ≥ 169 at baseline (HR = 0.67, 95% CI 0.25–1.80, P = 0.43) and at 6 weeks post treatment (HR = 0.69, 95% CI 0.25–1.86, P = 0.46). No statistically different PFS was found between patients with SII < 730 and those with SII ≥ 730 at baseline (HR = 0.70, 95% CI 0.26–1.89, P = 0.48) and at 6 weeks post treatment (HR = 0.38, 95% CI 0.013–1.09, P = 0.07). In conclusion, NLR at 6 weeks after start of treatment appears to be a biomarker of response in the early phase in SCLC patients treated with anti-PD-1/PD-L1 antibodies as second- or later-line treatment.

目的 探究肿瘤内科“四生”培训的策略及其效果,为“四生”培训工作的开展提供参考依据.方法 采用考核评分和调查评估的方法,分析本院肿瘤内科个性化“四生”培训工作开展前后的理论和实践考核成绩,调查“四生”对培训模式的认可情况.结果 个性化“四生”培训工作开展后,理论和实践考核成绩均高于培训后,差异有统计学意义(P＜0.05).个性化“四生”培训工作开展后,“四生”各自评情况均优于开展前,差异有统计学意义(P＜0.05).结论 肿瘤内科个性化“四生”培训的开展,对“四生”综合素质的提升和医疗工作的开展均有重要意义.

Objective:To observe the baseline characteristics and clinical efficacy in cancer patients who were treated with immune checkpoint inhibitors (ICIs) and experienced immune-related adverse events (irAEs).Methods:The clinical efficacy in cancer patients experiencing irAEs was retrospectively analyzed, and the objective response rate, progression-free survival, and overall survival were evaluated.Results:The median onset time of irAEs in 23 patients was 3.17 months. There were 47.8% (11/23) patients with multi-system irAEs, 63.3% (7/11) of which were non-simultaneous. The most common irAEs were immune-related pneumonia, hypothyroidism and immune-related liver dysfunction. Complete remission, partial remission and stable disease were respectively achieved in 0, 10 and 11 cases, while the other two patients developed progressive disease. The objective response rate was 43.5% and the disease control rate was 91.3%. With a median follow-up period of 16.5 months, 17 patients (73.9%) had progressive disease and the median progression-free survival was 9.63 months. Eight patients (34.8%) died before reaching the median overall survival. The progression-free survival and overall survival of patients with irAEs ≥grade 3 were significantly shorter than those with irAEs of grade 1-2 ( P<0.01). Conclusions:The occurrence of irAEs might correlate with the short-term efficacy and clinical benefits in patients treated with ICIs.