Treatment Of Carcinoma Research Articles

1700P Impact of sarcomatoid (S) and rhabdoid (R) components (comp.) on the efficacy of nivolumab (N) +/- ipilimumab (I) in the first-line (L1) treatment of metastatic clear cell renal cell carcinoma (mRCC) in the randomized phase II BIONIKK trial

1700P Impact of sarcomatoid (S) and rhabdoid (R) components (comp.) on the efficacy of nivolumab (N) +/- ipilimumab (I) in the first-line (L1) treatment of metastatic clear cell renal cell carcinoma (mRCC) in the randomized phase II BIONIKK trial

PE091 Laparoscopic radical nephroureterectomy with open bladder cuff excision vs. complete robotic approach for the treatment of upper urinary tract urothelial carcinoma: Our experience

PE091 Laparoscopic radical nephroureterectomy with open bladder cuff excision vs. complete robotic approach for the treatment of upper urinary tract urothelial carcinoma: Our experience

Identification of genome-wide copy number variation-driven subtypes for the treatment and prognostic prediction of esophageal carcinoma

BackgroundEsophageal carcinoma (ESCA) is a frequently detected gastrointestinal cancer. Copy number variants (CNVs) have a dramatic impact on the screening, diagnosis and prognostic prediction of cancers. However, the mechanism of action of CNVs on ESCA occurrence and progression remains unclear. MethodsESCA samples from The Cancer Genome Atlas (TCGA) were typed by consensus clustering using CNV-associated genes. Weighted Gene Co-Expression Network Analysis (WGCNA) was used to section gene modules closely related to the two clusters, and sub-networks were constructed as hub genes. In addition, seven prognosis-correlated genes were further screened and retained by multivariate Cox regression analysis to develop a prognostic assessment model. The ssGSEA algorithm assessed energy metabolism levels in patients from different clusters and risk groups. Finally, quantitative real-time PCR (qRT-PCR) and live-dead cell staining verified the expression of genes associated with CNV risk scores. ResultsESCA was classified into two subtypes based on CNV values. Compared with cluster 1, cluster 2 had significantly higher level of immune score and tumor-associated immune cell infiltration as well as a noticeably better overall survival. The three modules most associated with the two clusters were identified by WGCNA, and a prognostic model with a strong prediction performance was constructed with their genes. Glycolysis, lactate metabolism, fatty acid synthesis, glutathione, methionine, and tryptophan metabolic pathway enrichment scores were remarkably higher in patients in cluster 1 and the high-risk group than in cluster 2 and the low-risk group. ConclusionThe current research maybe provides new understanding for the pathogenesis of ESCA based on CNV, providing an effective guidance for its clinical diagnosis and prognostic evaluation.

853MO Setanaxib plus pembrolizumab for the treatment of recurrent or metastatic squamous cell carcinoma of the head & neck: Results of a randomized, double-blind phase II trial

853MO Setanaxib plus pembrolizumab for the treatment of recurrent or metastatic squamous cell carcinoma of the head & neck: Results of a randomized, double-blind phase II trial

954P Evaluation of antigen-specific CD8 T cell responses to predict efficacy of atezolizumab and bevacizumab treatment in hepatocellular carcinoma

954P Evaluation of antigen-specific CD8 T cell responses to predict efficacy of atezolizumab and bevacizumab treatment in hepatocellular carcinoma

Real-world evaluation of nivolumab utilization in adjuvant treatment of localized muscle-invasive urothelial carcinoma

Introduction: In 2022, nivolumab was granted marketing authorization for adjuvant treatment in patients at high risk of recurrence following surgery for localized invasive muscle urothelial carcinoma, who express PD-L1 on the operative specimen. We aimed to investigate its real-world utilization.Materials and methods: Our bi-centric real-world study, conducted at Foch Hospital and Georges Pompidou European Hospital between July 2022 and January 2024, included patients who underwent surgery for urothelial carcinoma or were referred for adjuvant nivolumab treatment at these centers.Results: A total of 200 patients underwent surgery during the study period, of whom 70 met the high-risk criteria, with 46% of these patients not receiving adjuvant treatment due to ineligibility. Our survival outcomes among patients treated by nivolumab are consistent with the results of the CheckMate 274 study2 (Bajorin DF, N Engl J Med. 2021). Our study population was older and frailer than that of the study cohort, with a mean age of 69 years. Significant PD-L1 expression was observed in 66% of the tested patients. The median disease-free survival was 11.34 months in patients who received neoadjuvant chemotherapy followed by surgery and adjuvant nivolumab. Nivolumab was generally well-tolerated, but 25% of patients discontinued it due to toxicity. Our initial data on treatments for recurrence after adjuvant nivolumab highlighted the effectiveness of conventional chemotherapy (cisplatin or carboplatin combined with gemcitabine) and targeted chemotherapy (enfortumab vedotin).Conclusion: Our real-world data align with existing literature regarding adjuvant nivolumab in localized invasive muscle urothelial carcinoma

974P Surufatinib combined with anti-PD-1/PD-L1 antibody in the second-line or monotherapy in third-line treatment of advanced hepatocellular carcinoma: A single-arm, open-label, multi-center phase II study

974P Surufatinib combined with anti-PD-1/PD-L1 antibody in the second-line or monotherapy in third-line treatment of advanced hepatocellular carcinoma: A single-arm, open-label, multi-center phase II study

Cancer and Hidradenitis Suppurativa

Hidradenitis suppurativa patients have an increased risk of developing cancer. This includes not only hematologic malignancies and solid tumors, but also cutaneous squamous cell carcinoma originating within the hidradenitis suppurativa lesions. The development of squamous cell carcinoma is most commonly associated with Caucasian men who smoke and have severe gluteal or perianal lesions of more than 25 years duration. Other factors that have occasionally been associated with hidradenitis suppurativa-related squamous cell carcinoma include treatment with a tumor necrosis factor-alpha inhibitor (such as infliximab and adalimumab), genodermatoses (such as keratitis-ichthyosis-deafness syndrome and Dowling-Degos disease), and paraneoplastic syndromes (such as hypercalcemia, hypercalcemia-leukocytosis, and paraneoplastic neuropathy). The tumor may demonstrate the presence of human papillomavirus; even after treatment, patients have a poor prognosis since cancer metastasis, or recurrence, or both commonly occurs. The potential role of human papillomavirus vaccination for cancer prevention and early treatment of squamous cell carcinoma with targeted therapy (with an epidermal growth factor inhibitor such as cetuximab) and/or checkpoint inhibitor immunotherapy (such as cemiplimab and pembrolizumab) remains to be determined. Rarely, hidradenitis suppurativa lesions have mimicked cutaneous metastases in patients with visceral malignancy by demonstrating an increased uptake of fluorine-18 fluorodeoxyglucose on positron emission tomography and/or computerized tomography scans. Also, both primary cancers (such as cutaneous squamous cell carcinoma and mucinous adenocarcinoma) and breast cancer skin metastases can masquerade as hidradenitis suppurativa lesions. Therefore, when a lesion is located at a current or prior site of hidradenitis suppurativa that is new or rapidly growing and/or does not respond to hidradenitis suppurativa-directed therapy, prompt evaluation to establish or exclude the diagnosis of cancer should be considered.

Effect of Niosomal Encapsulation of Quercetin and Silymarin and their Combination on Dimethylnitrosoamine-induced and Phenobarbital promoted Hepatocellular Carcinoma in Rat Model.

Hepatocellular carcinoma is a particularly dangerous and severe kind of liver cancer. Many anticancer drugs fail to complete the treatment of hepatocellular carcinoma without any side effects. There should be appropriate and without side effective treatments for hepatocellular carcinoma. The objective of the current study was to evaluate how quercetin and silymarin in a niosomal formulation affected hepatocyte carcinoma caused by diethylnitrosamine. Five groups were created from the thirty male rats. Normal control (untreated group), tumor group (administered dimethylnitrosoamine 200 mg/kg), treatment group I (administered 50 mg/kg of niosomal encapsulated quercetin), treatment group II (administered 50 mg/kg of niosomal encapsulated silymarin), and treatment group III (administered 50 mg/kg of niosomal encapsulated quercetin + silymarin). Then, biochemical estimation, serum analysis, and histopathological examination were carried out. Treatment group III, treated with niosomal encapsulation of a combination of quercetin + silymarin 50 mg/kg, demonstrated the significant restoration of alpha-fetoprotein and carcinoembryonic antigen and also antioxidants like superoxide dismutase and nitric oxide. The histopathological examination showed improved liver architecture in this group compared to other treatment groups. Our findings revealed that a potent anticancer effect was observed in treatment group III as niosomal formulation increased the bioavailability of the drug within the body. In order to completely understand the underlying processes and evaluate the therapeutic effectiveness of these chemicals in the therapy of hepatocellular carcinoma, further investigation and clinical trials are required.

51708 Associations of Social Vulnerability on Treatment and Outcomes of Cutaneous Squamous Cell Carcinoma of the Head and Neck

51708 Associations of Social Vulnerability on Treatment and Outcomes of Cutaneous Squamous Cell Carcinoma of the Head and Neck

Sorafenib and SIAIS361034, a novel PROTAC degrader of BCL-xL, display synergistic antitumor effects on hepatocellular carcinoma with minimal hepatotoxicity

The overexpression of BCL-xL is closely associated with poor prognosis in hepatocellular carcinoma (HCC). While the strategy of combination of BCL-xL and MCL-1 for treating solid tumors has been reported, it presents significant hepatotoxicity. SIAIS361034, a novel proteolysis targeting chimera (PROTAC) agent, selectively induces the ubiquitination and subsequent proteasomal degradation of BCL-xL through the CRBN-E3 ubiquitin ligase. When combined with sorafenib, SIAIS361034 showed a potent synergistic effect in inhibiting hepatocellular carcinoma development both in vitro and in vivo. Since SIAIS361034 exhibits a high degree of selectivity for degrading BCL-xL in hepatocellular carcinoma, the hepatotoxicity typically associated with the combined inhibition of BCL-xL and MCL-1 is significantly reduced, thereby greatly enhancing safety. Mechanistically, BCL-xL and MCL-1 sequester the BH3-only protein BIM on mitochondria at baseline. Treatment with SIAIS361034 and sorafenib destabilizes BIM/BCL-xL and BIM/MCL1 association, resulting in the liberation of more BIM proteins to trigger apoptosis. Additionally, we discovered a novel compensatory regulation mechanism in hepatocellular carcinoma cells. BIM can rapidly respond to changes in the balance between BCL-xL and MCL-1 through their co-transcription factor MEF2C to maintain apoptosis resistance. In summary, the combination therapy of SIAIS361034 and sorafenib represents an effective and safe approach for inhibiting hepatocellular carcinoma progression. The novel balancing mechanism may also provide insights for combination and precision therapies in the treatment of hepatocellular carcinoma

2021TiP INTerpath-005: Phase II study of pembrolizumab (pembro) with V940 (mRNA-4157) versus pembro with placebo (pbo) for adjuvant treatment of resected high-risk muscle-invasive urothelial carcinoma (MIUC)

2021TiP INTerpath-005: Phase II study of pembrolizumab (pembro) with V940 (mRNA-4157) versus pembro with placebo (pbo) for adjuvant treatment of resected high-risk muscle-invasive urothelial carcinoma (MIUC)

Luteolin exerts anti-tumour immunity in hepatocellular carcinoma by accelerating CD8+ T lymphocyte infiltration.

Luteolin, a commonly used traditional Chinese medicine, has been utilized for several decades in the treatment of hepatocellular carcinoma (HCC). Previous research has demonstrated its anti-tumour efficacy, but its underlying mechanism remains unclear. This study aimed to assess the therapeutic effects of luteolin in H22 tumour-bearing mice. luteolin effectively inhibited the growth of solid tumours in a well-established mouse model of HCC. High-throughput sequencing revealed that luteolin treatment could enhance T-cell activation, cell chemotaxis and cytokine production. In addition, luteolin helped sustain a high ratio of CD8+ T lymphocytes in the spleen, peripheral blood and tumour tissues. The effects of luteolin on the phenotypic and functional changes in tumour-infiltrating CD8+ T lymphocytes were also investigated. Luteolin restored the cytotoxicity of tumour-infiltrating CD8+ T lymphocytes in H22 tumour-bearing mice. The CD8+ T lymphocytes exhibited intensified phenotype activation and increased production of granzyme B, IFN-γ and TNF-α in serum. The combined administration of luteolin and the PD-1 inhibitor enhanced the anti-tumour effects in H22 tumour-bearing mice. Luteolin could exert an anti-tumour immune response by inducing CD8+ T lymphocyte infiltration and enhance the anti-tumour effects of the PD-1 inhibitor on H22 tumour-bearing mice.

739. SIGNIFICANCE OF COX2 INHIBITOR FOR ESOPHAGEAL CANCER FROM THE CLINICAL AND EXPERIMENTAL ESTIMATE

Abstract (Aims) We report experimental and clinical evidence that COX2 represent a potential molecular target for the treatment and prevention of esophageal cancer. (Methods) (A)Experiment: Thirty 8-week male wistar rats were exposed to duodenal content esophageal reflux. All animal underwent an esophagoduodenal anastomosis (EDA) with total gastrectomy in order to produce chronic esophagitis. In ten rats the sham (Control). They were sacrified at 40th week. Their esophagi were examined for HE, COX2,PGE2, PCNA and total bile acids in the esophageal lumen was measured. (B)Clinical: The expression of COX2 was examined for 68 specimens of esophageal squamous cell carcinoma (SCC) and the correlation of COX2 expression with clinicopatholigic features was examined. (Results) (A) After 40 weeks of reflux, columnar dysplasia, squamous cell carcinoma and adenocarcinoma were found. Total bile acid in the esophageal lumen was significantly increased in the EDA group compared with the sham operated rats. PCNA LI and esophageal tissue PGE2 were higher in dysplastic and cancer tissue than that of control. Overexpression of COX2 was shown in dysplastic and cancer tissue. COX2 may play an important role in esophageal cancer by duodenal content reflux.(B) COX2 immunoreactivity was weak in 27(40%) and strong in 41(60%) of the carcinomas. The proportion of poorly differentiated SCC among tumors with a strong expression of COX2 (34%) was significantly higher than among tumors with a weak expression of COX2 (19%, p=0.02). The depth of tumors (p=0.004), lymph node metastasis (p=0.0009) and the stage of the tumors (p=0.001) were advanced significantly more progressively in ECCS with a strong COX2 expression. Moreover, survival was significantly reduced (p=0.02) among patients with strong COX2 expression when compared with the COX2 weak group. This study showed that strong expression of COX2 was correlated with tumor progression and poor differentiation in ESCC. (Conclusion) In this experimental study, we demonstrate that bile reflux of duodenal contents induce COX2 and increase prostaglandin synthesis in dysplastic and cancer tissue. Our study suggests that COX2 may play a role in esophageal carcinoma development and progression, COX2 inhibitors may be potential targets for the prevention or treatment of esophageal carcinoma.

Targeted delivery of cisplatin magnetic nanoparticles for diagnosis and treatment of nasopharyngeal carcinoma

Rapid advances in nanotechnology are paving the way for innovative breakthroughs in overcoming the current limitations in the clinical treatment of cancer and other prevalent diseases plaguing mankind. Magnetic nanoparticles composed of iron oxide (Fe3O4) are a novel class of nanoparticles that are receiving increasing attention in the field of cancer therapy. To address the inherent limitations, bare Fe3O4 can be functionalized, polymerized, assembled, or combined with other functional materials to produce a range of smart nanoplatforms suitable for tumor therapy. In this paper, we present a unique multifunctional therapeutic nanoplatform centered on aldehyde-oxidized sodium alginate-stabilized iron oxide nanoparticles (NPs) designed for T2-weighted magnetic resonance (MR) imaging. Sodium alginate oxide and ferric oxide nanoparticles were prepared respectively, and the two particles were mixed in a certain molar ratio to form a complex, which was coupled to target polypeptide GE11 by Schiff base reaction, and finally supported by cisplatin through coordination complexation. The prepared magnetic nanoparticles (hereinafter referred to as GE11-CDDP-ASA@Fe3O4) have an average diameter of 152.9nm, and have good colloidal stability and cytocompatibility. The distinctive structure and composition of GE11-CDDP-ASA@Fe3O4 contribute to its excellent MRI imaging performance, positioning it as a nano platform suitable for enhancing the efficacy of combination therapy in tumor treatment. This is of great significance for translational nanomedicine applications.

1417P Comparative efficacy and safety of tislelizumab versus anti-PD-1 treatments in second-line esophageal squamous cell carcinoma: Simulated treatment comparisons

1417P Comparative efficacy and safety of tislelizumab versus anti-PD-1 treatments in second-line esophageal squamous cell carcinoma: Simulated treatment comparisons

396. SHORT-TERM REVIEW: REAL-WORD EXPERIENCE OF PEMBROLIZUMAB AS FIRST-LINE CHEMOTHERAPY FOR ADVANCED ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background In Japan, Pembrolizumab, combined with standard chemotherapy (fluorouracil and cisplatin), was approved for first-line treatment of esophageal squamous cell carcinoma (ESCC) in November 2021. In advanced ESCC cases, modifications like omitting cisplatin or adding the palliative radiotherapy for malignant stenosis are sometimes necessary. The real-world application of Pembrolizumab with chemotherapy (Pem+C) in these scenarios remains uncertain. This review presents an overview of Pem+C’s short-term clinical outcomes in practice. Methods We retrospectively studied nineteen patients treated with Pem+C as the first-line chemotherapy for advanced ESCC from Nov. 2021 to Dec.2023. Response evaluation was primarily based on RECIST v1.1. Clinical worsening factored into some progression disease (PD) assessments. Adverse events were graded using CTC-AE v5.0. Kaplan-Meier survival curves were calculated by SPSS, with data cutoff on Dec. 31. 2023. Results Median age was 70 (49-83 years), PS (0/1/2):0/8/1, TPS (1≤/1≤/NE):1/2/16. Disease Status (Recurrence [locoregional/distant metastasis] /metastatic):3 [2/1] /16. Sequence of treatments (Pem+C alone/ concurrent palliative radiotherapy (pRT) consisting of 30-40Gy/ maintenance after chemoradiotherapy ):10/5/4. Three received only fluorouracil as backbone chemotherapy due to frailty. Median follow-up time, overall survival (OS) and progression free survival (PFS) were 8.3, 14.4, and 6.5 months, respectively. Responses in evaluable eighteen (CR/PR/nonCRnonPD/SD/PD):2/8/1/3/4. No unexpected severe adverse events (≥Grade3) were found. Among limited cases, concurrent pRT didn’t increased life-threatening AE; however, neutropenia ≥G3 seemed to be slightly frequent (2/5). One patient’s survival exceeded 24.8 months. Conclusion Our real-world experience with Pem+C in advanced ESCC includes diverse approaches clinical practices. The outcomes, while prelimiary, compare favorably with existing literature, without significant inferiority. The safety data and success case in the concurrent pRT group are significant, though limited by the small number of cases and short observation period. While further, more rigorous studies are necessary, adaptable Pem+C could be viable in practice.

Investigating synergy between beta-blockers and transarterial chemoembolization in the treatment of hepatocellular carcinoma: preliminary data from a propensity matched analysis

PurposeFavorable clinical outcomes have been reported with the adjunct use of beta-blockers in cancer treatment, hypothetically secondary to their anti-angiogenic/anti-proliferative effects. Hereby, we investigate whether there is synergy between beta-blockers and TACE in the treatment of HCC. Methods36 HCC patients on beta-blockers (mean dose of 48 mg daily) at the time of first-line treatment with TACE at our institution were retrospectively identified out of a cohort of 221 patients between 2008 and 2019. Using propensity scoring, a matched cohort of 36 patients not exposed to beta-blockers was generated based on age, gender, ethnicity, etiology of liver disease, BCLC, child Pugh score, PS/ECOG, cirrhosis, largest mass treated, type of TACE and treated liver segments. Tumor response was assessed at 1st and 2nd post-TACE imaging timepoints (1.4 and 4.1 months on average respectively). Variables were compared using chi-square test and Student's t-test. Kaplan-Meier transplant-free survival plots were generated using IBM® SPSS® software. Cox regression analysis was used to evaluate survival predictors. A p values < 0.05 was considered significant. ResultsComparing the control and beta-blocker cohorts, there were no differences in baseline characteristics, post-TACE imaging timepoints, tumor response or transplant free survival (p > 0.05). Tumor size was found to be a predictor of survival when the two cohorts were combined (p = 0.03). ConclusionTransplant-free survival and HCC response to first-line TACE treatment were similar in the control and beta-blocker groups. Large tumor sizes were associated with higher mortality in combined analysis of the cohorts.

Efficacy of Combination Therapy of Lenvatinib and New FP for the Treatment of Unresectable Advanced Hepatocellular Carcinoma: A Case Report

Efficacy of Combination Therapy of Lenvatinib and New FP for the Treatment of Unresectable Advanced Hepatocellular Carcinoma: A Case Report

1974P A phase II trial of intravesical cabazitaxel, gemcitabine, and cisplatin (CGC) for the treatment of non-muscle invasive BCG unresponsive urothelial carcinoma of the bladder

1974P A phase II trial of intravesical cabazitaxel, gemcitabine, and cisplatin (CGC) for the treatment of non-muscle invasive BCG unresponsive urothelial carcinoma of the bladder