Therapy For Carcinoma Research Articles

Lichen spinulosus in a patient undergoing Atezolizumab therapy for metastatic squamous cell lung carcinoma

Lichen spinulosus in a patient undergoing Atezolizumab therapy for metastatic squamous cell lung carcinoma

CAR-T cell therapy for hepatocellular carcinoma: current trends and challenges

Hepatocellular carcinoma (HCC) ranks among the most prevalent cancers worldwide, highlighting the urgent need for improved diagnostic and therapeutic methodologies. The standard treatment regimen generally involves surgical intervention followed by systemic therapies; however, the median survival rates for patients remain unsatisfactory. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a pivotal advancement in cancer treatment. Both clinical and preclinical studies emphasize the notable efficacy of CAR T cells in targeting HCC. Various molecules, such as GPC3, c-Met, and NKG2D, show significant promise as potential immunotherapeutic targets in liver cancer. Despite this, employing CAR T cells to treat solid tumors like HCC poses considerable challenges within the discipline. Numerous innovations have significant potential to enhance the efficacy of CAR T-cell therapy for HCC, including improvements in T cell trafficking, strategies to counteract the immunosuppressive tumor microenvironment, and enhanced safety protocols. Ongoing efforts to discover therapeutic targets for CAR T cells highlight the need for the development of more practical manufacturing strategies for CAR-modified cells. This review synthesizes recent findings and clinical advancements in the use of CAR T-cell therapies for HCC treatment. We elucidate the therapeutic benefits of CAR T cells in HCC and identify the primary barriers to their broader application. Our analysis aims to provide a comprehensive overview of the current status and future prospects of CAR T-cell immunotherapy for HCC.

Axl and EGFR Dual-Specific Binding Affibody for Targeted Therapy in Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) is a tumor of the head and neck, with a higher incidence in southern China and Southeast Asia. Radiotherapy and chemotherapy are the main treatments; however, metastasis and recurrence remain the main causes of treatment failure. Further, the majority of patients are diagnosed in the late stage due to lack of tumor-specific biomarker for early diagnosis. Therefore, an effective treatment and early detection can improve the outcome of patient with NPC. Axl and EGFR are co-expressed in NPC tissues and play key roles in tumor proliferation, migration, and invasion, which are often correlated with poor prognosis and therapy resistance. In this study, we generated a novel bispecific affibody (Z239-1907) for the dual targeting and inhibition of Axl and EGFR expression in NPC-positive cells both in vitro and in vivo. The in vitro experiments demonstrated that Z239-1907 had more pronounced antitumor effects than either modality alone (ZAXL239 or ZEGFR1907) in NPC-positive cells. Further, mice bearing NPC-positive tumors showed significant inhibition in tumor growth after treatment with Z239-1907 compared to ZAXL239 and ZEGFR1907. The in vivo tumor targeting ability and imaging also showed that Z239-1907 specifically and selectively targeted NPC xenograft mice models and accumulate at tumor site as early as 30 min and disappeared within 24 h post-injection. Collectively, these results suggest that Z239-1907 dual-target affibody is a promising therapeutic agent and a molecular imaging probe for early diagnosis in NPC.

A Graphene-Based Lipid Modulation Nanoplatform for Synergetic Lipid Starvation/Chemo/Photothermal Therapy of Oral Squamous Cell Carcinoma

A Graphene-Based Lipid Modulation Nanoplatform for Synergetic Lipid Starvation/Chemo/Photothermal Therapy of Oral Squamous Cell Carcinoma

Hyaluronic acid-functionalized MOFs for combined sunitinib and siRNA therapy in renal cell carcinoma

Sunitinib is a first-line treatment for renal cell carcinoma (RCC), but suffers from drug resistance, causing therapy failure. Therefore, nano-scale delivery systems should be introduced for targeted delivery. Metal-organic frameworks (MOFs) are attractive drug carriers that not only enable multidrug combination therapies but also exert photodynamic effects by incorporating photosensitizers as components. Here, a Zr-based porphyrinic nanoscale MOF, PCN224, was prepared as the carrier for the co-delivery of sunitinib and the siRNA against vascular endothelial growth factor receptor-2 (VEGFR-2). Drug-loaded PCN-224 is coated with hyaluronic acid (HA) to prevent drug molecular leakage and to exert tumor-targeting effects (CD44 in tumor cells). Photodynamic therapy was conducted under 660 nm laser (50 mW·cm−2, 10 min) irradiation. Compared with St/siVEGFR-2@PCN-224@HA without the HA coating, St/siVEGFR-2@PCN-224@HA significantly suppressed cell viability and promoted cell apoptosis. Laser irradiation further increased the anti-cancer effect of St/siVEGFR-2@PCN-224@HA by generating cytotoxic ROS. H&E staining of major organs revealed no signs of damage, indicating the biosafety of St/siVEGFR-2@PCN-224@HA. The prepared St/siVEGFR-2@PCN-224@HA system enables triple inhibition of tumor growth via a combination of targeted therapy and genetic and photodynamic therapy to enhance the therapeutic effects on RCC.

P201 Finding the best second-line: TKI vs IO after TKI in first-line systemic therapy in advanced renal cell carcinoma: Experience of three Portuguese centers

P201 Finding the best second-line: TKI vs IO after TKI in first-line systemic therapy in advanced renal cell carcinoma: Experience of three Portuguese centers

Prognostic Prediction and Risk Stratification of Transarterial Chemoembolization Combined with Targeted Therapy and Immunotherapy for Unresectable Hepatocellular Carcinoma: A Dual-Center Study

Prognostic Prediction and Risk Stratification of Transarterial Chemoembolization Combined with Targeted Therapy and Immunotherapy for Unresectable Hepatocellular Carcinoma: A Dual-Center Study

Landscape of targeted therapies for lung squamous cell carcinoma

Lung cancer, a common type of malignant neoplasm, has seen significant advancements in the treatment of lung adenocarcinoma (LUAD). However, the management of lung squamous cell carcinoma (LSCC) continues to pose challenges. Traditional treatment methods for LSCC encompass surgical resection, chemotherapy, and radiotherapy. The introduction of targeted therapy and immunotherapy has greatly benefited LSCC patients, but issues such as limited immune response rates and adverse reactions persist. Therefore, gaining a deeper comprehension of the underlying mechanisms holds immense importance. This review provides an in-depth overview of classical signaling pathways and therapeutic targets, including the PI3K signaling pathway, CDK4/6 pathway, FGFR1 pathway and EGFR pathway. Additionally, we delve into alternative signaling pathways and potential targets that could offer new therapeutic avenues for LSCC. Lastly, we summarize the latest advancements in targeted therapy combined with immune checkpoint blockade (ICB) therapy for LSCC and discuss the prospects and challenges in this field.

Avelumab reduces STAT3 expression with effects on IL-17RA and CD15.

Avelumab is a human antibody that targets the programmed cell death ligand-1 (PD-L1) protein in cancer cells. Novel anticancer therapies for renal cell carcinoma (RCC) consider cluster of differentiation 15 (CD15) and interleukin 17 receptor A (IL-17RA) as potential targets. Notably, the expression of PD-L1, CD15 and IL-17RA is dependent on signal transducer and activator of transcription 3 (STAT3). The aim of the study was to investigate whether targeting PD-L1 with avelumab alters the expression levels of CD15 and IL-17RA, and to assess the STAT3-mediated regulation of CD15 and IL-17RA. We applied immunocytochemistry (ICC) and confocal laser scanning (CLS) microscopy to assess the expression and localization of the immunotherapy targets in 3 renal cancer cell lines and 1 healthy renal cell line. After treatment with 20 ng/mL avelumab, renal cancer cells showed a reduction in STAT3 expression. The expression of CD15 increased in cancer cells that exhibited a high level of IL-17RA, and the membrane signal of CD15 was reduced. In other renal cancer cell lines, the expression of CD15 decreased. Conversely, the level of IL-17RA changed only in healthy renal cells after treatment with avelumab, with no impact on renal cancer cells. Our study suggests that the targeting of PD-L1 with avelumab alters the expression of CD15 and IL-17RA, which play an important prognostic and therapeutic role in novel anticancer therapy.

Efficacy and safety of lenvatinib and pembrolizumab as first-line treatment for advanced renal cell carcinoma patients: real-world experience in Japan.

Combined treatment with lenvatinib and pembrolizumab is currently regarded as one of the standard first-line therapies for advanced renal cell carcinoma (aRCC) patients. The objective of this study was to assess the efficacy and safety of this combined regimen in treatment-naïve Japanese aRCC patients. This study included a total of 50 consecutive aRCC patients receiving combined lenvatinib plus pembrolizumab in routine clinical practice in Japan, and comprehensively analyzed clinical outcomes of this treatment. Of these 50, 7 (14.0%), 23 (46.0%) and 20 (40.0%) were classified into favorable, intermediate and poor risk groups, respectively, according to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) system. Responses to this combined therapy in the 50 patients were as follows: complete response, 7 (14.0%); partial response, 26 (52.0%); stable disease, 15 (30%) and progressive disease, 2 (4%); thus, the objective response rate (ORR) was 66%. ORRs in favorable, intermediate and poor risk groups were 57.1, 69.6 and 65.0%, respectively. During the observation period, disease progression and death occurred in 14 (28.0%) and 6 (12.0%) patients, respectively, and neither the median PFS nor OS was reached. Adverse events and those corresponding to grade ≥ 3 were observed in all (100%) and 33 (66.0%) patients, respectively. To our knowledge, this is the first study focusing on real-world outcomes of lenvatinib and pembrolizumab for treatment-naïve aRCC patients, showing that the efficacy and safety of this combined regimen are similar to those noted in randomized clinical trial.

WNT/β-catenin Signaling and CD8+ Tumor-infiltrating Lymphocytes in Tremelimumab Plus Durvalumab for Advanced Hepatocellular Carcinoma.

Tremelimumab plus durvalumab is an approved first-line therapy for advanced hepatocellular carcinoma (HCC). Previous studies identified WNT/β-catenin mutations or CD8+ tumor-infiltrating lymphocytes (TILs) as biomarkers that can predict responsiveness to immune checkpoint inhibitor therapy in HCC. However, biomarkers for effectiveness of tremelimumab plus durvalumab in HCC have not been reported. This study investigated whether evaluation of WNT/β-catenin signaling and CD8+ TILs by immunohistochemical staining of tumor biopsy tissues can predict the response to tremelimumab plus durvalumab in patients with HCC. Fifteen HCC patients who underwent tumor biopsies were classified into three groups based on WNT/β-catenin signal activation and CD8+ TIL infiltration. The clinical responses to treatment in the groups were evaluated. Four patients had HCC with WNT/β-catenin signal inactivation and high-level CD8+ TIL infiltration, four patients had HCC with WNT/β-catenin signal activation and low-level CD8+ TIL infiltration, and seven patients had WNT/β-catenin signal activation and high-level CD8+ TIL infiltration or WNT/β-catenin signal inactivation and low-level CD8+ TIL infiltration. A better response rate was observed in the WNT/β-catenin signal inactivation and high-level CD8+ TIL infiltration group, and a worse response rate was observed in the WNT/β-catenin signal activation and low-level CD8+ TIL infiltration group. Although the present study involved a small number of patients, the findings suggest that the efficacy of tremelimumab plus durvalumab may be affected by WNT/β-catenin signaling and CD8+ TIL infiltration.

Usefulness of Upfront Neck Dissection Before Chemoradiation Therapy for Head and Neck Squamous Cell Carcinoma.

Locally advanced squamous cell carcinoma of the head and neck (L/A SCCHN) is typically treated with surgery or chemoradiation therapy (CRT), whereas salvage surgery is considered for residual disease post-CRT. However, salvage surgery after radiation therapy presents challenges due to tissue fibrosis. Planned neck dissection (ND) combined with CRT, as well as positron emission tomography after CRT, have been proposed strategies, but no definitive consensus has been reached. Therefore, this study aimed to investigate the utility of "upfront ND" performed prior to CRT to enhance local control and reduce complications. We retrospectively reviewed 121 patients who underwent primary CRT for oropharyngeal, hypopharyngeal, or laryngeal cancer at Tokyo Medical University Hospital from January 2015 to September 2021. Patients without cervical lymph node metastasis or with unresectable nodes were excluded. All patients underwent pre-treatment imaging and staging. CRT consisted of intensity-modulated radiation therapy (IMRT) and cisplatin-based chemotherapy. Selective ND or modified radical neck dissection was performed based on lymph node involvement. Overall, 35 patients underwent upfront ND, whereas 54 did not. The upfront ND group exhibited significantly better 2-year locoregional recurrence-free survival than the group without upfront ND (93.7% vs. 71.0%). No significant differences were noted in adverse events between groups. The findings highlight upfront ND before CRT as a viable option for locally advanced head and neck cancer, particularly beneficial in cases with extranodal extension. This approach enhances local control and may reduce the need for salvage surgery, thus improving patient outcomes.

Immune checkpoint inhibitor therapy for primary neuroendocrine carcinoma of the gallbladder: A case report and literature review.

Gallbladder neuroendocrine carcinoma (GNEC) is indeed a relatively rare malignant tumor of the gallbladder with neuroendocrine differentiation and the ability to produce and secrete a number of neurotransmitters and hormones, characteristics that make its clinical presentation and biological behavior likely to be different from those of other types of gallbladder cancer. Current treatment mostly relies on surgery and adjuvant chemotherapy and radiotherapy. We report a 53-year-old middle-aged male patient who underwent radical surgery for gallbladder malignancy after a diagnosis of neuroendocrine carcinoma of the gallbladder. Diagnosis of neuroendocrine carcinoma of the gallbladder based on the return of pathologic findings. After local progression of postoperative chemotherapy with the first-line regimen of etoposide + cisplatin, an immune checkpoint inhibitor (traplizumab) + FOLIFIRI (fluorouracil + calcium folinate + irinotecan) regimen was used. The patient achieved 20 months of clinical survival and ultimately died of myelosuppression. The use of immune checkpoint inhibitors may become an effective tool in the treatment of neuroendocrine carcinoma of the gallbladder.

Lactylation-Driven IGF2BP3-Mediated Serine Metabolism Reprogramming and RNA m6A-Modification Promotes Lenvatinib Resistance in HCC.

Acquired resistance remains a bottleneck for molecular-targeted therapy in advanced hepatocellular carcinoma (HCC). Metabolic adaptation and epigenetic remodeling are recognized as hallmarks of cancer that may contribute to acquired resistance. In various lenvatinib-resistant models, increased glycolysis leads to lactate accumulation and lysine lactylation of IGF2BP3. This lactylation is crucial for capturing PCK2 and NRF2 mRNAs, thereby enhancing their expression. This process reprograms serine metabolism and strengthens the antioxidant defense system. Additionally, altered serine metabolism increases the availability of methylated substrates, such as S-adenosylmethionine (SAM), for N6-methyladenosine (m6A) methylation of PCK2 and NRF2 mRNAs. The lactylated IGF2BP3-PCK2-SAM-m6A loop maintains elevated PCK2 and NRF2 levels, enhancing the antioxidant system and promoting lenvatinib resistance in HCC. Treatment with liposomes carrying siRNAs targeting IGF2BP3 or the glycolysis inhibitor 2-DG restored lenvatinib sensitivity in vivo. These findings highlight the connection between metabolic reprogramming and epigenetic regulation and suggest that targeting metabolic pathways may offer new strategies to overcome lenvatinib resistance in HCC.

HLX07 alone or combined with serplulimab, cisplatin and 5-fluorouracil for advanced esophageal squamous cell carcinoma: A phase 2 study.

The combination of anti-PD-1 antibody serplulimab and chemotherapy is considered standard first-line therapy for advanced esophageal squamous cell carcinoma (ESCC), but few later-line treatments are available. Here we evaluated the therapeutic efficacy of the recombinant, humanized anti-EGFR antibody HLX07 when used alone or together with serplulimab and chemotherapy against advanced ESCC. This open-label, non-randomized, two-cohort, phase 2 trial involved patients 18-75 years old with histologically or cytologically confirmed locally advanced, unresectable, or metastatic ESCC, and an Eastern Cooperative Oncology Group performance status of 0-1. Patients who had failed first-line immuno-chemotherapy or at least two lines of other systemic therapy received HLX07 monotherapy intravenously at a dose of 1,000 mg once every 2 weeks (Q2W). Patients with no prior systemic therapy received HLX07 (1,000 mg, day 1) and serplulimab (200 mg, day 1) intravenously Q2W for up to 2 years, concurrently with cisplatin (50 mg/m2, day 1) for up to 8 cycles and 5-fluorouracil (1,200 mg/m2, days 1-2) for up to 12 cycles intravenously Q2W. The primary endpoints were progression-free survival (PFS) and objective response rate (ORR). Overall, 50 patients were enrolled. In the HLX07 monotherapy group, ORR was 15.0% (3/20), and the median PFS was 1.5 months (95% confidence interval [CI], 1.3 to 3.7). The median duration of response was not reached, and the rate of patients showing an objective response lasting at least 6 months was 66.7% (95% CI, 5.4 to 94.5). Two (10.0%, 2/20) patients experienced grade 3-4 treatment-related adverse events (TRAEs), including hypomagnesemia, hypocalcemia, and fatigue. No patient experienced grade 5 TRAEs. In the HLX07 combination group, the ORR was 60.0% (18/30), and the median PFS was 7.8 months (95% CI, 3.3 to 9.1). Fourteen (46.7%, 14/30) patients experienced grade 3-4 TRAEs, and one (3.3%, 1/30) patient died due to serplulimab-related pneumonitis. HLX07 monotherapy and its combination with serplulimab and chemotherapy showed manageable toxicity and promising antitumor activity in patients with recurrent or metastatic ESCC. Randomized controlled trials are warranted to further establish the safety and efficacy of HLX07 against ESCC. This trial was registered at Clinicaltrials.gov (NCT05221658).

Anti–Programmed Death Ligand 1 Plus Targeted Therapy in Anaplastic Thyroid Carcinoma

Anaplastic thyroid carcinoma (ATC) is a rare and lethal cancer. Although progress has been made in recent years in patients with mutated BRAF tumors, those who respond initially eventually die of their disease; furthermore, there are no approved therapies for non-BRAF mutated tumors. To determine whether treatment with matched-targeted therapy plus immune checkpoint inhibitors were associated with improved overall survival (OS). A phase 2 trial at a single center, tertiary institution with parallel cohorts, assigning treatment with targeted therapy according to the tumor mutation status. Patients with mutated BRAF V600E tumors received vemurafenib/cobimetinib plus atezolizumab (cohort 1); those with mutated RAS (NRAS, KRAS, or HRAS) or NF1/2 tumors received cobimetinib plus atezolizumab (cohort 2). Patients without any of these variants were assigned to receive bevacizumab plus atezolizumab (cohort 3). Patients were enrolled from August 3, 2017, to July 7, 2021. All consecutive, systemic therapy-naive patients with ATC with active disease and who met eligibility criteria were considered for participation. The analysis was conducted in September 2023. Patients were assigned to targeted therapy based on the driver mutation as follow: BRAF V600E (cohort 1, vemurafenib plus cobimetinib), RAS/NF (cohort 2, cobimetinib), or non-BRAF/RAS/NF (cohort 3, bevacizumab). All received atezolizumab. The primary outcome of the study was median OS of the entire targeted therapy cohort, compared with historical median OS of 5 months. Forty-three patients with ATC were enrolled in the targeted therapy cohorts, of which 42 were included in the primary analysis. The median OS in patients across these 3 cohorts was 19 months (95% CI, 7.79-43.24). Median OS and progression-free survival per cohort were as follows: cohort 1: 43 months (95% CI, 16-not estimable [NE]), 13.9 months (6.6-64.1); cohort 2: 8.7 months (95% CI, 5.1-37.0) and 4.8 months (1.8-14.7); cohort 3 (vascular endothelial growth factor inhibitor group): 6.21 months (4.1-NE) and 1.3 months (1.3-NE), respectively. In this nonrandomized clinical trial, atezolizumab combined with targeted therapy resulted in a longer median OS than historical landmark, achieving the study's primary end point, with cohort 1 achieving the longest OS. ClinicalTrials.gov Identifier: NCT03181100.

Intelligent Modular DNA Lysosome-Targeting Chimera Nanodevice for Precision Tumor Therapy.

Lysosome targeting chimeras (LYTACs) have emerged as a powerful modality that can eliminate traditionally undruggable extracellular tumor-related pathogenic proteins, but their low bioavailability and nonspecific distribution significantly restrict their efficacy in precision tumor therapy. Developing a LYTAC system that can selectively target tumor tissues and enable a modular design is crucial but challenging. We here report a programmable nanoplatform for tumor-specific degradation of multipathogenic proteins using an intelligent modular DNA LYTAC (IMTAC) nanodevice. We employ circular DNA origami to integrate predesigned modular multitarget protein binding sites and pH-responsive protein degradation promoters that specifically recognize cell-surface lysosome-shuttling receptors in tumor tissues. By precisely manipulating the stoichiometry and modularity of promoters and ligands targeting diverse proteins, the IMTAC nanodevice enables accurate localization and delivery into tumor tissues, where the acidic tumor microenvironment triggers degradation switch activation, multivalent binding, and efficient degradation of various prespecified proteins. The tissue-specificity and multiple ligands in IMTACs significantly improve the drug utilization rate while reducing off-target effects. Importantly, this system demonstrates the capability of collabo-rative degradation of EGFR and PDL1 in tumor tissue for combined targeting and immunity therapy of hepatocellular carcinoma (HCC), resulting in obvious tumor necrosis and inhibition of tumor growth in vivo even at low concentrations. This study presents a unique strategy for building a general, intelligent, modular, and simple encoded nanoplatform for designing precision medicine degraders and developing proprietary antitumor drugs.

Polymeric nanoparticles loaded with vincristine and carbon dots for hepatocellular carcinoma therapy and imaging

Chemotherapy for hepatoblastoma is limited by organ toxicity and poor outcomes, prompting the search for new, more effective treatments with minimal side effects. Vincristine sulfate, a potent chemotherapeutic, faces challenges due to P-glycoprotein-mediated resistance and its systemic toxicity. Nanoparticles offer a promising solution by improving pharmacokinetics, targeting tumor cells, thus reducing side effects. Moreover, the use of fluorescent nanomaterials is emerging in biomedical applications such as bioimaging, detection and therapies. This study describes a promising delivery system utilizing carbon dots encapsulated with vincristine in biodegradable polycaprolactone nanoparticles via a double emulsion technique. The fine characterization of these nanoparticles showed that they are spherical, uniformly sized with around 200 nm and exhibit excellent colloidal stability. Moreover, the release profile showed prolonged release for both vincristine and carbon dots. In vitro cell viability studies revealed enhanced cancer cell inhibition for the encapsulated drug compared to the vincristine solution. The uptake study indicated clear fluorescence for carbon dots solution and vincristine and carbon dots loaded nanoparticles upon excitation. Additionally, studies on primary mouse hepatocytes demonstrated higher fluorescence intensity in treatment groups. These results suggest that vincristine and carbon dots loaded nanoparticles are effective, target-specific carriers for liver cancer treatment. Furthermore, the carbon dots were not cytotoxic, highlighting their potential in bioimaging and cancer cell studies.

Phase Ib study of anti-PD-L1 monoclonal antibody socazolimab in combination with nab-paclitaxel as first-line therapy for advanced urothelial carcinoma.

PD-1/PD-L1 immune checkpoint inhibitors (ICIs) have demonstrated activity in the post-platinum and platinum-ineligible settings for advanced urothelial carcinoma (aUC). As only around 50% of patients with aUC can tolerate platinum-containing treatment, treatments combining first-line ICIs with non-platinum drugs are urgently needed. Therefore, we assessed the safety and efficacy of the anti-PD-L1 monoclonal antibody Socazolimab in combination with nab-paclitaxel as first-line therapy in aUC (NCT04603846). This was a multi-center, single-arm, phase Ib study that enrolled patients with treatment-naive aUC. Patients received Socazolimab (5mg/kg) and nab-paclitaxel (260mg/m2) Q3w. The primary endpoint was safety and tolerability of the combination regimen. Second endpoints were the objective response rate (ORR) and progression-free survival. Between September, 2020 and September, 2021, 20 patients with urothelial carcinoma were enrolled, arising from renal pelvis (5), bladder (8), and ureter (7). After a median follow-up of 17 months, the median number of treatment cycles was 12. No patients had dose limiting toxicity. All patients had treatment-related adverse events (TRAEs), most of which were grade 1 or 2. The common TRAEs (≥20%) were peripheral neurotoxicity, alopecia, rash, increased ALT, weight loss, weakness, pruritus, increased AST, increased γGT, increased ALP, neutropenia, emesis, and anorexia. Nine patients (45%) developed grade 3 TRAEs including peripheral neurotoxicity (30.0%), increased ALT (10.0%), and increased γGT (5.0%). Two patients (10%) discontinued treatment because of grade 3 mouth ulcer (n = 1) and grade 2 lung fibrosis (n = 1). No grade 4-5 TRAEs were observed. Among the 17 patients who had received at least one tumor assessment, ORR was 58.8% (95% CI, 32.9%-81.6%) and the median progression-free survival was 8.3 months (95% CI, 5.2-19.5). The median duration of response was 13.3 months (95% CI, 2.0-20.1), and the overall survival was 19.5 months (95% CI, 11.2-not reached). Socazolimab combined with nab-paclitaxel has shown good safety and promising antitumor activity as first-line therapy in patients with advanced urothelial carcinoma.

Clinical study on conversion therapy of hepatocellular carcinoma - summary and comparison of clinical data from a single center of consecutive four years

AimThe purpose of this study was to interpret real-world clinical data to analyze the surgical safety and survival outcomes of patients with initial unresectable hepatocellular carcinoma (uHCC) after conversion therapy.MethodsA retrospective analysis was performed on 2984 hepatocellular carcinoma (HCC) patients hospitalized in Shandong Cancer Hospital Affiliated to Shandong First Medical University from June 1st, 2019 to June 1st, 2023. Clinicopathological features, response to systemic and/or loco-regional treatments, surgical resection rate after conversion therapy, surgical safety, and postoperative recurrence were analyzed.ResultsA total of 38 patients were successfully converted to obtain surgical resection. 35 patients underwent radical resection. A high objective response rate (ORR) (52.6% under RECIST v1.1 and 78.9% under mRECIST criteria) was observed in patients under conversion therapy, and the disease control rate (DCR) was 100%. Pathologic complete response (pCR) was 42.9%. Treatment-related adverse events (TRAEs) of any grade were observed in 37 patients (97.4%). Safety of conversion or direct surgery continues to improve. The median follow-up time was 19.3 months. The 1-year Disease-free survival (DFS) rate of patients with direct surgery and patients with conversion surgery were 91.4% and 86.8%, respectively.ConclusionsWith conversion therapy, a small percentage (1.81%) of uHCC patients are likely to be converted to radical resection. Local combined systemic therapy is a relatively safe and effective conversion therapy, and the safety of surgery is gradually improved after successful conversion. Preliminary follow-up data showed satisfactory survival benefits for patients undergoing conversion surgery.Trial registrationThis was a retrospective study and it did not interfere with treatment decisions.