Median Progression-free Survival Time Research Articles

The Vascular Endothelial Growth Factor-A121/Vascular Endothelial Growth Factor-A165 Ratio as a Predictor of the Therapeutic Response to Immune Checkpoint Inhibitors in Gastric Cancer

Background/Objectives: The response rate to immune checkpoint inhibitor (ICI) therapy is limited. Further, there is a need to discover biomarkers to predict therapeutic efficacy. The vascular endothelial growth factor (VEGF) is strongly associated with intra-tumoral immunity; however, its utility as a marker remains unknown. Therefore, our objectives were to examine the isoforms of VEGF and determine whether VEGF levels predict ICI efficacy. Methods: Levels of VEGF isoforms VEGF-A121 and VEGF-A165 were measured in stored serum samples obtained from 30 patients with advanced or recurrent gastric cancer who received nivolumab monotherapy at Kagoshima University Hospital, and the association with prognosis and treatment efficacy was retrospectively analyzed. Results: The serum levels of the total VEGF, VEGF-A121, and VEGF-A165 were not significantly associated with prognosis. However, the ratio of VEGF-A121/VEGF-A165 (VEGF-A121/165) exhibited a statistically significant (p = 0.0088) difference in progression-free survival (PFS) with the low-ratio group having a 67-day prolonged median PFS time. Under univariable analysis, only VEGF-A121/165 values exhibited reduced progression-free survival with statistical significance. When comparing treatment responses in the low (n = 15) and high (n = 15) serum VEGF-A-121/165 groups, RECIST evaluation was 3 to 0 for complete response (CR), 2 to 0 for partial response (PR), 3 to 2 for stable disease (SD), and 3 to 10 for progressive disease (PD). Patients with clinically unsettled PR or SD were classified as non-CR/non-PD (4 vs. 3), with a disease control rate of 80% vs. 33%. Conclusions: The serum VEGF-A121/165 ratio may represent a new, easily measured biomarker for predicting the therapeutic response to ICIs.

Expression and clinical significance of FAT1 gene in pancreatic adenocarcinoma

Objective: To analyze the expression of FAT1 gene in pancreatic adenocarcinoma and its relationship with clinicopathological features, prognosis, and immunotherapy for pancreatic adenocarcinoma. Methods: (1) Bioinformatics analysis: based on FAT1 mRNA expression and clinical data of 179 cases of pancreatic adenocarcinoma in the TCGA database, and FAT1 mRNA expression data of 328 cases of normal pancreatic tissues in the GTEx database. We analyzed the differences in FAT1 mRNA expression in pancreatic adenocarcinoma and normal pancreatic tissues and the relationship between FAT1 mRNA expression and the degree of differentiation, clinical stage, prognosis, immune cell infiltration, and immune checkpoint-associated genes in pancreatic adenocarcinoma. FAT1-related differentially expressed genes were analyzed by applying Limma 3.40.2 software package, and GO and KEGG enrichment analysis was performed on the differentially expressed genes. Immunohistochemical (IHC) of FAT1 in pancreatic adenocarcinoma and normal pancreatic tissues was analyzed by HPA database. (2) Validation of own tissue samples: tissue samples and clinical and prognostic data of 192 patients with pancreatic ductal adenocarcinoma admitted to Zhejiang Cancer Hospital from March 8, 2010 to September 30, 2020 were collected. IHC was performed on the tissue samples to verify the protein expression of FAT1 in pancreatic adenocarcinoma and its relationship with immune-related proteins, the degree of differentiation of pancreatic adenocarcinoma, clinical staging, and prognosis. Results: (1) Bioinformatics analysis: the FAT1 mRNA expression of 179 pancreatic adenocarcinoma tissues from the TCGA database was 5.55±1.04, which was higher than that of 328 normal pancreatic tissues with FAT1 mRNA from the GTEx database (2.95±0.53, P＜0.001). FAT1-specific IHC images showed that FAT1 expression was generally high in pancreatic adenocarcinoma tissues, and FAT1 expression shifted from the cell membrane to the cytoplasm. The FAT1 mRNA expression in the highly differentiated group (31 cases), the moderately differentiated group (96 cases), and the lowly differentiated group (52 cases) were 4.99±1.46, 5.51±0.80, and 5.68±1.08, the expression of pancreatic adenocarcinoma tissues were all higher than that of normal pancreatic tissues (all P＜0.001), and the FAT1 mRNA expression of the moderately differentiated group and the poorly differentiated group were all higher than that of the highly differentiated group (all P＜0.001). The median progression-free survival time (PFS) and median overall survival time (OS) of the 90 patients in the FAT1 mRNA low-expression group were 16.5 and 24 months, respectively, which were longer than those of the 89 patients in the FAT1 mRNA high-expression group (median PFS and OS were 13 and 18 months, respectively; P-values were 0.011 and 0.005, respectively). Multifactorial Cox regression analysis showed that FAT1 mRNA expression level was an independent influencing factor for OS in pancreatic adenocarcinoma patients (HR=1.47, 95% CI: 1.09-1.99). Correlation analysis showed that FAT1 mRNA expression in pancreatic adenocarcinoma was positively correlated with B-cell infiltration, CD8+ T-cell infiltration, neutrophil infiltration, macrophage infiltration, and myeloid dendritic cell infiltration (ρ=0.27, P＜0.001; ρ=0.28, P＜0.001; ρ=0.32, P＜0.001; ρ=0.21, P=0.004; ρ=0.32, P＜0.001), and also positively correlated with mRNA expression of CD274, HAVCR2, and PDCD1LG2 (r=0.327, P＜0.001; r=0.231, P=0.002; r=0.258, P＜0.001). GO and KEGG enrichment analyses showed that FAT1 mRNA expression levels were associated with activation of the Wnt signaling pathway (P=0.029), the PI3K/Akt pathway (P<0.001), and other tumor microenvironment-related pathways. (2) Validation of own tissue samples: among 192 pancreatic adenocarcinoma tissues, FAT1 was highly expressed in 58 cases (30.21%), and the proportion of FAT1-expressing positive tumor cells was positively correlated with the combined positive score of PD-L1 and the number of CD3+ T-cells infiltration (r=0.154, P=0.032; r=0.287, P＜0.001), and the protein expression of FAT1 had no correlation with the differentiation degree of pancreatic adenocarcinoma (ρ=0.082, P=0.254). The median OS of 58 patients in the FAT1 high-expression group and 134 patients in the FAT1 low-expression group were 18.89 and 25.84 months, respectively, and the difference was not statistically significant (χ²=1.93, P=0.165). Conclusion: FAT1 gene is highly expressed in pancreatic adenocarcinoma tissues, may play an oncogenic role in pancreatic adenocarcinoma, may be an adverse influence on overall survival and progression-free survival of patients; FAT1 gene may be involved in multiple immune-related pathways and promote tumor immune escape.

Sequential Use of Sorafenib and Regorafenib in Hepatocellular Cancer Recurrence After Liver Transplantation: Treatment Strategies and Outcomes.

During liver transplantation, hepatocellular carcinoma (HCC) recurrence remains a critical challenge for patient survival. Targeted therapies, such as sorafenib and regorafenib, have been utilized to manage relapsed HCC in this unique setting. This study aimed to assess the efficacy of Sorafenib and Regorafenib in patients with HCC who experienced recurrence after liver transplantation. We focused on survival outcomes, treatment responses, and the management of side effects in this patient group. We conducted a retrospective analysis of 73 patients who experienced HCC recurrence post-liver transplantation between 2012 and 2022 across 11 oncology centers in Turkey. Patients were categorized according to Child-Pugh classification and treated with sorafenib as first-line therapy and Regorafenib in case of progression. Survival rates were analyzed using the Kaplan-Meier method, and risk factors were evaluated using Cox regression analysis. Of the 73 patients included in the study, 62 were male (84.9%), and 11 were female (15.1%), with a mean age of 61.5 ± 10.9 years. All patients received sorafenib as first-line treatment. Among patients who experienced progression with sorafenib or discontinued treatment due to toxicity, 45.2% (n = 33) continued treatment with regorafenib. The median progression-free survival (PFS1) time with sorafenib was 5.6 months, and the one-year survival rate was 24.3%. The median progression-free survival (PFS2) time with regorafenib, which was administered as second-line treatment, was also calculated as 5.9 months. Overall survival (OS) duration was determined as 35.9 months. The most common side effects associated with both drugs included fatigue, hand and foot syndrome, and hypertension. Significantly better survival outcomes were shown in the Child-Pugh A group compared to other patients. These results suggest that Sorafenib and Regorafenib treatments offer a survival advantage in patients with relapsed HCC post-transplantation. However, individualized treatment strategies and close follow-up are crucial for optimizing outcomes. Further studies are needed to refine therapeutic protocols and enhance the care of this specific patient group.

Clinical Benefits of Photodynamic Therapy Using Talaporfin Sodium in Patients With Isocitrate Dehydrogenase-Wildtype Diagnosed Glioblastoma: A Retrospective Study of 100 Cases.

Photodynamic therapy (PDT) with talaporfin sodium is an intraoperative local therapy administered after the surgical removal of malignant gliomas. However, its clinical efficacy in a large patient population has not been determined. To analyze the clinical outcomes and prognosis in isocitrate dehydrogenase (IDH)-wildtype glioblastoma patients treated with PDT. This retrospective study included patients with newly diagnosed IDH-wildtype glioblastoma treated at Kobe University Hospital between January 2013 and December 2022. PDT involves irradiation of the resection cavity with a 664-nm semiconductor laser after an intravenous infusion of talaporfin sodium. The main outcome measures were the recurrence patterns and survival times, which were compared between the PDT and non-PDT groups. Univariate and multivariate analyses were used to determine the prognostic factors. In addition, adverse events and prognostic factors in the PDT group were analyzed. A total of 44 and 56 patients were included in the PDT and non-PDT groups, respectively. The local recurrence rate was significantly lower in the PDT group than in the non-PDT group (51.3% vs 83.9%), whereas the distant recurrence and dissemination rates were significantly higher in the PDT group than in the non-PDT group (48.7% vs 16.1%). Two grade 3 adverse events were observed in the PDT group. The median progression-free survival and overall survival times were significantly longer in the PDT group than in the non-PDT group (progression-free survival: 10.8 vs 9.3 months, respectively, and overall survival: 24.6 vs 17.6 months, respectively). Multivariate analysis of the PDT groups revealed that younger age was an independent prognostic factor. PDT with talaporfin sodium provided effective local control with minimal adverse effects. The survival time of the patients treated with PDT was significantly longer than that of the patients who did not receive PDT. Therefore, a randomized controlled clinical trial on PDT is warranted.

Transarterial chemoembolization combined with molecular targeted agents plus immune checkpoint inhibitors for unresectable hepatocellular carcinoma beyond the up-to-seven criteria: a propensity score-matching analysis

Purpose Not all patients benefit from transarterial chemoembolization (TACE) due to the heterogeneity of the tumour burden in intermediate-stage hepatocellular carcinoma (HCC). To compare the outcomes of transarterial chemoembolization (TACE) combined with molecular-targeted agents plus immune checkpoint inhibitors (TACE-MTAs-ICIs) with those of TACE for patients with unresectable hepatocellular carcinoma (uHCC) that were beyond the up-to-seven criteria. Patients and methods Between January 2019 and July 2022, 130 patients diagnosed with uHCC beyond the up-to-seven criteria were retrospectively identified, including 47 patients who received TACE-MTAs-ICIs and 83 patients who received TACE alone. The primary endpoints were overall survival (OS) and progression-free survival (PFS); the secondary endpoints included tumour response and adverse events (AEs). Results There were 43 matched patients. The median OS and PFS times in the TACE-MTAs-ICIs group were significantly longer than those in the TACE group (OS: 27.2 vs. 15.9 months, p = 0.007; PFS: 15.4 months vs. 4.8 months, p < 0.001). The objective response rate (ORR) in the TACE-MTAs-ICIs group was higher than that in the TACE group (65.1% vs. 37.2%, p = 0.010). Reversible AEs (grade 3 or 4) occurred differently in TACE-MTAs-ICIs and TACE groups (83.7% vs. 51.2%, p = 0.001). Univariate and multivariate analyses revealed that TACE-MTAs-ICIs treatment was an independent favourable prognostic factor for both PFS and OS (p < 0.001). Conclusion For uHCC patients beyond the up-to-seven criteria, TACE-MTAs-ICIs provided superior ORR and OS. Early combined TACE and systemic treatment should shift for patients who are beyond these criteria.

Clinical characteristics and prognostic factors of epidermal growth factor receptor-mutated non-small cell lung cancer transformed into small-cell lung cancer after treatment

Objective: To analyze the clinical characteristics and prognostic factors of non-small cell lung cancer (NSCLC) patients with sensitive epidermal growth factor receptor (EGFR) mutations who developed small cell lung cancer (SCLC) transformation after treatment with EGFR tyrosine kinase inhibitors (TKI). Methods: We conducted a retrospective collection of clinical data for 21 patients with advanced EGFR mutant NSCLC who developed SCLC transformation after EGFR-TKI treatment at Beijing Chest Hospital, Capital Medical University from January 2015 to December 2021. The clinical characteristics were summarized and the prognosis analysis was conducted. Patients were followed up until February 2024. The efficacy was evaluated using Solid Tumor Response Evaluation Criteria, and survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the differences in survival time (OS) between limited stage and extensive stage in transformed SCLC patients. Cox proportional hazards model was used to analyze the influencing factors of survival after SCLC transformation. Results: Among the 21 patients, there were 5 males and 16 females, with an age range of 33-74 years old [(58.9±2.6) years old]. All 21 patients were adenocarcinoma with sensitive EGFR mutations. There were 18 cases (85.7%) with EGFR gene 19del mutation, including 1 case of 19del+anaplastic lymphoma kinase (ALK) mutation, and 3 cases of L858R mutation. Among the transformed SCLC, there were 11 cases of pure SCLC and 10 cases of mixed SCLC (coexisting of adenocarcinoma and small cell carcinoma components). The median time from diagnosis of NSCLC to SCLC transformation was 12.0 months (95%CI: 7.6-16.3 months). Among the 21 cases of SCLC transformation, there were 13 cases with the extensive stage and 8 cases with the limited stage. Among them, 16 patients received systemic chemotherapy based on etoposide, of which 13 cases could be evaluated for efficacy, 11 cases could be calculated for PFS. Five cases had partial remission, 5 cases were stable, 3 cases had disease progression, and 3 cases cloud not be evaluated. The median progression free survival time (PFS) was 4.8 months (95%CI: 2.8-6.8 months). The median survival time (OS) after SCLC transformation in 21 patients was 10.6 months (95%CI: 7.0-14.2 months), with a median OS of 8.8 months (95%CI: 6.3-11.4 months) for patients with the extensive stage and 27.5 months (95%CI: 9.6-34.4 months) for patients with the limited stage, with statistically significant differences (P=0.002). Cox proportional hazards model analysis showed that the limited stage after SCLC transformation was a protective factor for OS (HR=0.32, 95%CI: 0.12-0.73, P=0.010). The median OS of 21 patients from the diagnosis of lung cancer was 24.9 months (95%CI: 13.0-36.7 months). Conclusions: NSCLC patients with SCLC transformation are all adenocarcinomas, and the proportion of EGFR19del mutations is relatively high. After SCLC transformation, the standard chemotherapy regimen for SCLC is generally used for treatment. The OS after SCLC transformation is related to the stage, and the prognosis is better in the limited stage.

Comparative Analysis of Concurrent Chemoradiotherapy Versus Chemotherapy Alone as First-Line Palliative Treatments for Advanced Esophageal Squamous Cell Carcinoma.

Background: In advanced-stage esophageal squamous cell carcinoma (ESCC), treatment of both the primary tumor and metastatic sites is imperatively required. Consequently, an optimal treatment modality should effectively control both aspects. Therefore, the benefits of concurrent chemoradiotherapy (CCRT) in cases of advanced-stage ESCC should be evaluated. Methods: This retrospective study compared the efficacy and safety of CCRT versus chemotherapy alone for advanced-stage ESCC patients from January 2012 to December 2023 at a university hospital in Southern Thailand. Survival was assessed using the Kaplan-Meier approach, with comparisons being made by the log-rank test. A p-value of <0.05 indicated statistical significance. Results: From a total of 196 patients with stage IV ESCC, 117 (59.7%) received CCRT, while 79 (40.3%) received chemotherapy alone. The median overall survival (OS) time was 9.04 months for CCRT and 5.79 months for chemotherapy (hazard ratio, HR: 0.58 [0.43-0.78]). CCRT significantly improved OS time in stage IVA patients (HR: 0.52 [0.29-0.93]), but not in stage IVB patients (HR: 0.76 [0.51-1.11]). The median progression-free survival (PFS) time was 6.04 months for CCRT and 3.50 months for chemotherapy (HR 0.48 [0.35-0.65]). The objective response rates (ORRs) were 43.6% and 22.8%, respectively (p = 0.003). Hematological toxicities were more common with CCRT, along with mild cases of treatment-associated pneumonitis and dermatitis. Conclusions: Although palliative chemotherapy is the standard treatment for advanced-stage ESCC, CCRT provides significant benefits for patients with stage IVA ESCC, improving OS, PFS, and ORRs, despite there being a higher incidence of adverse events. Thus, CCRT should be considered for patients with stage IVA ESCC with a good performance status.

Clinicopathological and molecular genetic insights into EBV-positive inflammatory follicular dendritic cell sarcoma

Epstein-Barr virus (EBV)-positive inflammatory follicular dendritic cell (FDC) sarcoma (EBV + IFDCS) is a rare entity, and its histopathological characteristics have not been fully described. This study aimed to investigate the clinical characteristics, pathological features, and molecular genetic profiles of EBV + IFDCS to improve our understanding of these lesions. A total of 12 EBV + IFDCS specimens were obtained from patients in our pathology diagnostic center. The clinical data, morphology, immunohistochemistry, in situ hybridization, and high-throughput DNA-targeted sequencing data were collected, and follow-up data were analyzed. These data were compared with those of 6 patients with traditional FDCS. The patients with EBV + IFDCS ranged from 21 to 84 years old, with a mean age of 52.3 years and a male-to-female ratio of 1:5. At the last follow-up, all patients were alive, with 2 experiencing recurrence and metastasis. In these cases, four were classified as the classical subtype, four as the angiomatoid/sclerosing subtype, and four as the lymphoma-like subtype, with two cases also exhibiting epithelioid granulomas. All patients exhibited heterogeneous expression of follicular dendritic cell markers (CD21, CD23, CD35, and CXCL13) alongside the fibroblast marker SMA, with significantly higher expressions of IgG4, EBER, and SMA in EBV + IFDCS patients compared to FDCS patients (P < 0.05). Conversely, SSTR2, EGFR, and STAT3 expression were significantly lower in the EBV + IFDCS group (P < 0.05). The average value of EBER was significantly higher in the classical subtype group (P = 0.022). Among the four cases of EBV + IFDCS analyzed for molecular genetic features, one patient exhibited germline mutations in the CDKN1C, PDGFRA, MSH2, FANCG, MLH1, ALK, and RUNX1 genes; three exhibited simultaneous SNP variations in the MTHFR gene; and two exhibited simultaneous SNP variations in the NQO1 gene. We conducted KEGG pathway analysis on the mutant genes, revealing significant enrichment in the cAMP signaling pathway, which plays a crucial role in tumor development. Survival analysis demonstrated that the median PFS rates were not reached (NR) for EBV + IFDCS patients, compared to 5 months (HR = 7.76) for FDCS patients. The 3-year PFS rates were 66.67% and 16.67%, respectively. Compared with the FDCS group, EBV + IFDCS patients had a significantly longer median PFS time (p < 0.05). In conclusion, EBV + IFDCS represents a group of tumors with unique clinical, morphological, immunological, prognostic, and molecular cytogenetic characteristics.

Effect of deep testosterone reduction on the prognosis of metastatic prostate cancer with high-volume disease

ObjectiveThis study aims to investigate the correlation between serum testosterone levels after one month of treatment and prognosis in patients with high-volume disease metastatic prostate cancer (mPCa) who are undergoing combined androgen blockade therapy (CAB).MethodsThe clinical data of 199 patients with high-volume disease mPCa, diagnosed through biopsy pathology and imaging, were retrospectively analyzed from January 2010 to October 2022 in the Department of Urology at the First Affiliated Hospital of Xinjiang Medical University. Among these patients, 111 cases had a deep reduction in serum testosterone (< 0.7 nmol/l) after one month of treatment, while 88 cases did not achieve a deep reduction (≥ 0.7 nmol/l). The study utilized the Kaplan–Meier method to plot survival curves and employed the multifactor COX regression model to analyze independent risk factors. The risk factors with a significance level of P < 0.05 in the multivariate analysis were included in the nomogram prediction model. The accuracy of the model was assessed using the ROC curve and the calibration curve, while the net benefit for patients was evaluated through the decision curve analysis (DCA).ResultsThe group that achieved deep testosterone reduction(DTR) had a higher proportion of PSA < 0.2 ng/ml and a greater PSA decline rate after six months of treatment (P < 0.05). The group that achieved DTR and the group that did not achieve DTR had a progression to castration resistant prostate cancer(CRPC) time of 17.93 ± 6.68 months and 13.43 ± 6.12 months, respectively (P < 0.001). The median progression-free survival time for the 2 groups were 18 months and 12 months, respectively (P < 0.001). The median overall survival times were 57 months and 32 months, respectively (P < 0.001). The median progression-free survival times were 18, 15, and 10 months for the group that achieved DTR within 1 month, the group that achieved DTR beyond 1 month but within 1 year, and the group that did not achieve DTR within 1 year, respectively (P < 0.001), and the median survival times were 57, 45, and 26 months, respectively (P < 0.001). COX multivariate analysis revealed that a testosterone level of ≥ 0.7 nmol/l at 1 month of treatment is an independent risk factor for the progression to CRPC and prognosis in patients with high-volume disease mPCa (P < 0.05). The risk of death in patients with a testosterone level of ≥ 0.7 nmol/l at 1 month of treatment was 2.087 times higher than that of patients with a level of < 0.7 nmol/l (P < 0.05). A nomogram prediction model was developed using independent risk factors, with the area under the ROC curve (AUC) for progression-free survival (PFS) at 12, 15, 18, and 21 months being 0.788, 0.772, 0.760, and 0.739, respectively. For 3 and 5 years, the AUCs for overall survival (OS) were 0.691 and 0.624. The calibration curve demonstrated good consistency between the model’s predicted values and the actual outcomes.ConclusionPatients with high-volume disease mPCa who receive CAB treatment may experience extended progression-free survival and overall survival if their serum testosterone levels are below 0.7 nmol/l after one month of treatment. The longer it takes to achieve DTR, the worse the patient’s prognosis may be. The nomogram prediction model developed in this study demonstrates good predictive ability in assessing the progression and prognosis of high-volume disease mPCa.

Randomized Phase II Trial of Amrubicin Plus Irinotecan Versus Cisplatin Plus Irinotecan in Chemo-naïve Patients With Extensive-Disease Small-Cell Lung Cancer: Results of the Japan Multinational Trial Organization (JMTO) LC 08-01

BackgroundWe conducted a randomize phase II study to evaluate the efficacy and safety of topoisomerase II inhibitor amrubicin plus topoisomerase I inhibitor irinotecan (AI) compared with cisplatin plus irinotecan (PI) as first-line therapy in patients with extensive-disease (ED) small-cell lung cancer (SCLC). Patients and MethodsChemo-naïve patients with pathologically proven ED-SCLC (including limited disease (LD) SCLC with malignant effusion) were enrolled. Patients were randomized 1:1 to receive either AI (amrubicin 90mg/m2 on day 1 and irinotecan 50mg/m2 on days 1 and 8 of a 21-day cycle) or PI (cisplatin 60mg/m2 on day 1 and irinotecan 60mg/m2 on days 1, 8 and 15 of a 28-day cycle). The primary endpoint was overall survival proportion at 1 year. ResultsA total of 100 patients were randomly assigned to AI (n = 50) or to PI (n = 50). The 1-year overall survival proportions were 68.0% (95% confidence interval (CI): 56.2-82.2%) for AI and 59.2% (46.9-74.7%) for PI (1-sided P = .18). Median survival time was 14.8 months for AI and 13.5 months for PI with a hazard ratio (HR) of 0.618 (0.398-0.961, stratified log-rank test P = .031). Median progression-free survival time was 4.8 months for AI and 5.4 months for PI (stratified log-rank test, P = .54). Objective response rate was 70.0% (55.4-82.1%) for AI and 55.1% (40.2-69.3%) for PI (Fisher exact test, P = .15). There was no significant difference in hematological toxicity, whereas rates of vomiting, loss of appetite, diarrhea, and elevated serum creatinine are more frequent in PI. Interstitial lung disease (Grade 2 or 3) developed in 5 patients in AI and in 1 patient in PI. There was no treatment-related death. ConclusionAlthough the study did not meet its primary endpoint, AI showed promising efficacy and good tolerability in chemo-naïve patients with ED-SCLC.

Analysis of Therapeutic Efficacy and Adverse Prognostic Factors of Secondary Central Nervous System Lymphoma

To explore the therapeutic efficacy and prognostic factors of induction therapy for secondary central nervous system lymphoma (SCNSL). Clinical data of patients diagnosed with SCNSL from 2010 to 2021 at Guangdong Provincial People's Hospital were retrospectively collected. A retrospective cohort study was performed on all and grouped patients to analyze the efficacy and survival. Multivariate logistic regression analysis was used to explore the adverse prognostic factors. Thirty-seven diffuse large B-cell lymphoma patients with secondary central involvement were included in the research. Their 2-year overall survival (OS) rate was 46.01% and median survival time was 18.1 months. The 2-year OS rates of HD-MTX group and TMZ group were 34.3% and 61%, median survival time were 8.7 and 38.3 months, and median progression-free survival time were 8.1 and 47 months, respectively. Multivariate logistic regression analysis showed that age, sex, IPI, Ann Arbor stage were correlated with patient survival time. The median survival time of patients with CD79B, KMT2D, CXCR4, ERBB2, TBL1XR1, BTG2, MYC, MYD88, and PIM1 mutations was 8.2 months, which was lower than the overall level. HD-MTX combined with TMZ as the first-line strategy may improve patient prognosis, and early application of gene sequencing is beneficial for evaluating prognosis.

Outcomes and prognostic factors in canine T cell lymphoma treated with lomustine, vincristine, cyclophosphamide, and prednisone chemotherapy

BackgroundThe most common first-line treatment for canine lymphoma is a chemotherapy protocol that includes cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Canine high-grade T-cell lymphoma has been found to have a significantly poorer prognosis than high grade B-cell lymphoma. Several studies have investigated alternative protocols for non-indolent T-cell lymphoma. This retrospective study investigated using a cyclophosphamide, lomustine, vincristine, and prednisone protocol (CLOP) for naïve non-indolent T-cell lymphoma patients.MethodsIn this retrospective study, medical records of dogs treated for non-indolent T-cell lymphoma at a veterinary teaching hospital from 2017 to 2022 were reviewed. Response rate, toxicity, progression-free survival and survival time were calculated. Factors potentially related to prognosis were statistically analyzed.ResultsTwenty-six dogs were included in the study. The median progression-free survival (PFS) time was 166 days (95% CI 119–213). The median overall survival time (OST) for the whole study group was 318 days (95% CI 239–374). Twenty-four dogs experienced gastrointestinal adverse events during the protocol, with 79% of them being grade 1 or 2 as per VCOG-CTCAE v2.ConclusionsThis protocol has shown similar median PFS time and OST compared with previous studies for canine non-indolent T-cell lymphoma treated with CHOP, along with minimal toxicity, and suggests the inclusion of lomustine in first-line chemotherapy protocol against canine non-indolent T-cell lymphoma may be beneficial.

Efficacy and safety of transcatheter arterial chemoembolization followed by hepatic arterial infusion chemotherapy combined with TKI and PD-1 inhibitors as first-line treatment for advanced hepatocellular carcinoma

To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) followed by hepatic arterial infusion chemotherapy (HAIC) combined with TKI drugs and PD-1 inhibitors as the first-line treatment for advanced hepatocellular carcinoma (HCC). We retrospectively analyzed the data of 70 patients with advanced HCC treated in the Department of Oncology of Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine between July, 2020 and June, 2023. 23 of the patients received TACE combined with HAIC and TKI (TACE+HAIC+ TKI group) and 47 received TACE combined with HAIC, PD-1 inhibitors and TKI (TACE+HAIC+PD-1+TKI group). The clinical characteristics, laboratory test results, efficacy, outcomes and adverse events of the patients were compared between the two groups. The TACE+HAIC+TKI and TACE+HAIC+PD-1+TKI groups had significantly different objective remission rates (ORR; 60.87% vs 36.17%, P=0.031), comparable disease control rates (95.65% vs 93.62%, P=0.068), and different median progression-free survival (PFS) time (10.2 vs 11.8 months, P=0.003) and median overall survival (OS) time (15.7 vs 19.5 months, P=0.035). After propensity score matching (PSM), the median PFS and OS time of the two groups was 10.1 vs 14.5 months (P= 0.024) and 14.2 vs 21.2 months (P=0.221), respectively. The 1-year PFS rates of the 2 groups were 24.0% vs 52.2%, and the 1-, 2-and 3-year OS rates were 72.3% vs 93.1%, 23.9% vs 63.8%, and 23.9% vs 36.5%, respectively. The incidence of proteinuria was significantly higher in TACE+HAIC+PD-1+TKI group than in TACE+HAIC+TKI group (21.28% vs 0, P=0.025), but the incidences of grade 3-4 treatment-related adverse events were all similar between the two groups. The first-line treatment with TACE+HAIC+PD-1+TKI is safe and effective for advanced HCC and can significantly prolong the survival of the patients.

Circulating tumor DNA (ctDNA) as a biomarker of response to therapy in advanced Hepatocellular carcinoma treated with Nivolumab.

Circulating tumor DNA (ctDNA) is a promising non-invasive marker for detection, diagnosis, treatment selection, and prognosis of hepatocellular carcinoma (HCC). This study aimed to examine the utility of ctDNA as a prognostic and predictive tool in HCC patients treated with nivolumab. We analyzed pre-treatment ctDNA from 44 HCC patients using comprehensive genomic testing on a commercially available platform. We utilized log rank test and univariate Cox models to correlate overall survival (OS) and progression-free survival (PFS) with ctDNA expressions. Of 44patients, 77.3% were men with median age of 67years. All but 3patients had at least one alteration identified, and TP53 was the most commonly altered gene (52.3%). Median OS was 17.5months (95% CI: 12.7, NA). Mutations involving PIK3CA, BRCA1, and CCND1 amplification were associated with shorter OS (P 0.0001, 0.0001 and 0.01, respectively). Median PFS time was 4.01months (95% CI: 3.06, 9.33). Mutations involving KIT and PIK3CA were associated with shorter PFS (P 0.0001 and 0.0004, respectively), while mutation involving CTNNB1 were associated with longer PFS (p= 0.04). ctDNA profiling may provide a benefit for prediction of survival and progression of HCC patients treated with nivolumab. Future studies are needed for confirmation.

Comparison of efficacy between anti-PD-1 antibody monotherapy and nivolumab plus ipilimumab therapy as first-line immunotherapy for advanced mucosal melanoma in Japanese patients: A single-center, retrospective cohort study.

Mucosal malignant melanoma (MMM) is a rare subtype of malignant melanoma with a more aggressive biological behavior than cutaneous melanoma (CM). Owing to its rarity, it is necessary to accumulate information on treatments, especially in Asians, in whom MMM occurs more frequently than in Caucasians. In this study, we investigated the efficacy and adverse events (AEs) of nivolumab plus ipilimumab therapy (NIVO+IPI) versus immune checkpoint inhibitor (ICI) monotherapy (PD-1) in Japanese patients with MMM. We reviewed patients with advanced or recurrent MMM who received ICIs as first-line systematic therapy between February 2012 and February 2024 at the Shizuoka Cancer Center. We enrolled a total of 57 patients: 10 (17.5%) were treated with NIVO+IPI, and 47 (82.5%) were treated with PD-1 as first-line systemic therapy. Objective response rates (ORR) did not differ significantly between the NIVO+IPI and PD-1 groups (40.0% vs 27.7%; p = 0.176). There was also no statistically significant difference in progression-free survival (PFS) (median PFS time: 4.3 months vs 9.9 months, log-rank test, p = 0.578) or overall survival (OS) (median OS time: 33.1 months vs. 22.8 months, log-rank test, p = 0.697) between the two groups. However, regarding AEs, grade ≥3 AEs leading to discontinuation of first-line treatment occurred in 80% of patients in the NIVO+IPI group and in 22.6% of patients in the PD-1 group (p = 0.002). No difference was found in the efficacy of NIVO+IPI therapy and anti-PD-1 antibody monotherapy as the first-line treatment for MMM in Japanese patients, but an increase in AEs was observed with combination therapy. This study suggests that patients with MMM may receive less benefit from NIVO+IPI than from PD-1.

Clinical Effects and Safety of Intra-Arterial Infusion Chemotherapy with Lipiodol versus Intra-Arterial Infusion Chemotherapy Alone for Treatment of Advanced Hepatocellular Carcinoma

Introduction: This study aimed to assess the effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) in 2 groups of patients: those who receive lipiodol (referred to as the lipiodol group) and those who do not receive lipiodol (referred to as the control group). Methods: From January 2016 through December 2023, 85 patients with advanced hepatocellular carcinoma were enrolled in this retrospective study. In total, 40 patients received HAIC with lipiodol, while 45 patients were given HAIC without lipiodol. The modified response evaluation criteria for solid tumors were used to evaluate the tumor response, which was assessed through an imaging study. The two groups were compared regarding their overall survival (OS), progression-free survival (PFS), and safety. Results: The outcomes between the lipiodol group and control group demonstrated no significant difference: the objective response rates (p = 0.066) were 32.5% and 15.6%; the disease control rates (p = 0.556) were 67.5% and 73.3%; the median OS times (p = 0.339) were 224 days and 398 days; the median PFS (p = 0.334) times were 191 days and 286 days in the lipiodol group and the control group, respectively. Adverse events also showed no significant difference between the two groups: elevation of total bilirubin (p = 0.834) rates were 40.0% and 37.8%; elevation of alanine aminotransferase (p = 0.191) percentages were 35.0% and 22.2%; and elevation of aspartate aminotransferase values (p = 0.058) were 65.0% and 44.4% in the lipiodol group and the control group, respectively. Conclusions: HAIC without lipiodol was non-inferior to HAIC with lipiodol in the clinical outcome.

Isolated Limb Infusion for Limb-Threatening Sarcomas.

Isolated limb infusion (ILI) treats unresectable extremity malignancies with high-dose regional chemotherapy limited to the limb. This study assessed long-term outcomes after ILI for limb-threatening sarcomas. A retrospective review analyzed patients with an extremity sarcoma who underwent ILI with melphalan and dactinomycin from 2008 to 2023 at a single institution. The study identified 61 patients (52.5% female; median age, 73 years; range, 20-94 years). Of these patients, 68.9% had lower-extremity disease. The median follow-up period was 6.9 years. The overall response rate was 48.3% (complete response [CR], 21.7%; partial response [PR], 26.7%), and the disease control rate (DCR: CR+PR+stable disease [SD]) was 65%. The median progression-free survival (PFS) for the patients with CR/PR/SD/progressive disease (PD) was respectively 16.8/9.6/4.8/2.4 months (P<0.0001). The responders (CR+PR) had significantly longer PFS than the non-responders (SD+PD) (hazard ratio [HR], 6.3; 95% confidence interval [CI], 3.1-12.9; P<0.001). The median in-field PFS times for CR/PR/SD/PD were respectively 16.8/12/4.8/2.4 months (P<0.001). The responders had a significantly longer risk of in-field PFS than the non-responders (HR, 5.9; 95% CI 2.9-12.0; P<0.001). The median distant relapse PFS for CR/PR/SD/PD was not reached (NR)/NR/44.4/40.8 months (P=0.02). The responders had a significantly longer distant relapse PFS than the non-responders (HR, 2.7; range, 1.1-6.8; P=0.04). The median overall survival (OS) was 8.6 years for the responders and 4.1 years for the non-responders (P=0.02). The disease-specific survival (DSS) rates were 87% at 1 year, 71% at 3 years, and 64% at 5 years. The median DSS was not reached for the responders and was 4.1 years for the non-responders (P=0.003). The limb salvage rates at 6 months were 85% at 1 year, 80% at 3 years, and 70% at 5 years. The patients with PD had a higher risk of requiring amputation than the patients with CR+PR+SD (HR, 3.0; 95% CI 1.0-8.7; P=0.04). The 5-year limb salvage rates after ILI are notably high, reaching 70%. After ILI, the responders had significantly better in-field and distant relapse PFS, OS, and DSS.

Enhanced platelet function through CAR-T cell therapy in relapsed/refractory multiple myeloma

The influence of chimeric antigen receptor T (CAR-T) cell therapy on platelet function in relapsed/refractory (R/R) multiple myeloma (MM) has not been thoroughly investigated. Our cohort comprised fifty MM patients treated with CAR-T cells. The mean platelet closure time (PCT) induced by collagen/adenosine diphosphate (CADP) in peripheral blood was significantly prolonged before lymphodepletion (195.24 ± 11.740 s) and notably reduced post-CAR-T cell therapy (128.02 ± 5.60 s), with a statistically significant improvement (67.22, 95% CI 46.91–87.53, P < 0.001). This post-treatment PCT was not significantly different from that of healthy controls (10.64, 95% CI 1.11–22.40, P > 0.05). Furthermore, a pronounced enhancement in PCT was observed in patients with a response greater than partial remission (PR) following CAR-T cell infusion compared to pre-treatment values (P < 0.001). An extended PCT was also associated with a less favorable remission status. In patients with cytokine release syndrome (CRS) grades 0–2, those with a PCT over 240.5 s exhibited a shorter progression-free survival (PFS), with median PFS times of 10.2 months for the PCT > 240.5 s group versus 22.0 months for the PCT ≤ 240.5 s group. Multivariate analysis revealed that a PCT value exceeding 240.5 s is an independent prognostic factor for overall survival (OS) in R/R MM patients after CAR-T cell therapy. The study demonstrates that CAR-T cell therapy enhances platelet function in R/R MM patients, and PCT emerges as a potential prognostic biomarker for the efficacy of CAR-T cell therapy.

Effect of Nivolumab on the Quality of Life in Recurrent/Metastatic Head and Neck Cancer.

Nivolumab is expected to further prolong survival and improve the quality of life (QOL) of patients with a poor prognosis of head and neck cancer. However, only a few studies have been conducted regarding the QOL of recurrent or metastatic head and neck cancer patients treated with nivolumab using real-world data. This study aimed to examine the effect of nivolumab on the QOL of these patients using real-world data. This study included patients with recurrent metastatic head and neck cancer who received nivolumab at the Department of Otolaryngology and Head and Neck Surgery, Tokyo Medical University Hospital from May 1, 2017, to December 31, 2021. Among them, 50 patients who self-assessed their QOL were included in this study. The primary endpoint was the QOL evaluation score, and secondary endpoints were overall survival (OS), progression-free survival (PFS), response rate, and immune-related adverse events. OS and PFS were evaluated using the Kaplan-Meier method. No significant reduction in QOL was observed before or after nivolumab administration. The median OS time was 20.1 months, and 1-year OS rate was 76.4%. The median PFS time was 4.2 months, and 1-year PFS rate was 31.0%. The comparison of patient QOL before and after nivolumab use suggested that patient QOL was not compromised. The results were not inferior to those of other studies in terms of treatment efficacy and safety.

Toripalimab plus chemotherapy and radiotherapy for treatment-naive advanced esophageal squamous cell carcinoma: a single-arm phase 2 trial

This single-arm phase 2 trial (ChiCTR2100046715) examined previously untreated patients with advanced esophageal squamous cell carcinoma (ESCC) who received four cycles of paclitaxel with carboplatin every 3 weeks. Toripalimab was infused intravenously every 3 weeks for 12 months, or until disease progression or intolerable toxicity. Radiotherapy that encompassed the primary lesions and metastases commenced in the third cycle. The median progression-free survival time was 9.8 months (95% confidence interval [CI]: 6.8–not estimable) in the intent-to-treat population, failing to meet the pre-specified primary endpoints. Secondary endpoints included an objective response rate of 45.5%, a disease control rate of 57.6%, and a median duration of response of 11.5 months (interquartile range, 6.4–15.0). The 1-year progression-free survival and overall survival rates were 41.9% (95% CI: 27.7–63.5) and 69.7% (95% CI: 55.7–87.3), respectively. Lymphopenia was the most frequent grade ≥3 adverse event (82%), and an esophageal fistula developed in three patients (9.1%). No treatment-related deaths occurred. In prespecified exploratory biomarker analysis, higher densities of CD8 + T cells, CD11c+ dendritic cells, and CD68+ macrophages correlated with improved tumor response and prognosis. Radiotherapy supplementation to first-line chemo-immunotherapy for treatment-naive advanced ESCC demonstrated some antitumor activity and manageable safety profiles, warranting further randomized controlled trials.