Progression-free Survival Time Research Articles

Long-term outcomes and prognostic factors in dogs with meningoencephalitis of unknown origin and suspected necrotic lesions on magnetic resonance imaging: 37 cases (2007-2020).

To describe the long-term outcomes, overall survival, progression-free survival, and prognostic factors in dogs with necrotizing encephalitis (NE). 37 client-owned dogs clinically diagnosed with NE. All dogs underwent MRI and CSF analysis. Cox proportional hazards regression was used to examine factors related to the risk of relapse and death, including signalment, history, diagnostic investigation results, and treatments before the first relapse. The medians of the overall and progression-free survival times were 639 days (IQR, 342 to 1,482 days) and 233 days (IQR, 111 to 775 days), respectively. Overall survival was highly correlated with progression-free survival. Four dogs (11%) died or were euthanized within 3 months of diagnosis. Relapse within 6 months was associated with a shorter overall survival. However, no prognostic factors for overall survival were found. The category of patients with presenting clinical signs that lasted 29 days to 6 months (OR, 3.26; 95% CI, 1.35 to 7.90) was associated with a higher risk of relapse. Seizures were presented in 75.7% of dogs, with a recurrence rate of 100%. This report provides comprehensive follow-up information for dogs with NE, revealing a fair prognosis and low early mortality rate. Seizure is a very common clinical sign with a high recurrence rate.

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.

TRAF4 promotes lung cancer development by activating tyrosine kinase of EGFR

Objective: To explore the role of tumor necrosis factor receptor-associated factor 4 (TRAF4) in promoting the abnormal activation of epidermal growth factor receptor (EGFR) and its effect on lung cancer cell proliferation, migration and invasion. Methods: Tumor tissues from patients who underwent lung adenocarcinoma resection at The First Affiliated Hospital of Second Military Medical University, from January 2015 to May 2017 were collected, and the expressions of TRAF4 and Ki-67 in lung cancer tissues were detected by immunohistochemistry, the mRNA levels of Cyclin D and Vimentin were detected by real-time fluorescence quantitative PCR (qRT-PCR). The effect of TRAF4 on the tumor growth ability of lung cancer A549 cells was investigated by the xenograft model, the effect of TRAF4 or EGFR on the tumor proliferation ability was detected by using cell counting kit 8 (CCK8) and BrdU assay, and the migration and invasion abilities of tumor cells were detected by Transwell assay. Different structural domain deletion expression vectors of TRAF4 and EGFR were constructed to transfect cells, and the interaction mode of TRAF4 and EGFR was investigated by immunoprecipitation assay. Results: The expression of TRAF4 in non-small cell lung cancer (NSCLC) tissues was positively correlated with the expressions of Ki-67, cyclin D, and vimentin (r2: 0.438, 0.695, and 0.736, respectively, all P＜0.01). Immunohistochemical assay of tumor tissues from NSCLC patients showed that tissues with high expression of TRAF4 were also high in Ki-67. Patients with high TRAF4 expression (TRAF4 positivity >30%) had a shorter progression-free survival (PFS) time than that of patients with low TRAF4 expression (TRAF4 positivity ≤30%) (median PFS of 12 and 19 months, respectively; P=0.034). Traf4-/- cells had a weakened proliferative capacity than traf4+/+ cells and formed tumors with smaller size (P＜0.05). The expression level of Ki-67 in the tumor tissues formed by traf4-/- cells [(45.6±8.7)%] was lower than that in the tumor tissues formed by traf4+/+ cells [(62.3±10.3)%, P=0.015], the mRNA levels of cyclin D (1.01±0.15) and vimentin (1.01±0.12) in the traf4-/- cells were lower than those of the traf4+/+ cells (3.41±0.32 and 3.12±0.18, respectively, both P＜0.05).The western blot results showed that, with the elevated intracellular expression level of TRAF4, phosphorylation level of EGFR was significantly increased in both wild-type EGFR and activation mutant EGFR-expression cells. The capacities of proliferation, migration and invasion of A549 cells was weakened after EGFR knockdown (all P＜0.01). Immunoprecipitation experiments showed that TRAF4 binds to the peptide segment of the near-membrane region of EGFR through the TRAF structural domain, and the mutual binding between EGFR molecules was enhanced under TRAF4 overexpression conditions. Increasing TRAF4 expression promoted EGFR molecular phosphorylation and activation of downstream signaling. Conclusions: TRAF4 expression is elevated in NSCLC tissues and tumor cells, which promotes tumor proliferation, migration and invasion. TRAF4 directly binds to EGFR molecules, enhances its own phosphorylation and activates the downstream signaling pathway by promoting the interaction between EGFR molecules.

VALIDATION OF 2HG-TARGETTED MR SPECTROSCOPY FOR IDENTIFYING IDH-MUTANT GLIOMAS

Abstract AIMS Diffuse gliomas, the most common adult primary brain tumour, are classified by their histological and molecular characteristics and genetic profile. Isocitrate dehydrogenase (IDH) mutant gliomas correlate with longer mean survival and progression-free survival time. In tumour cells, IDH mutations lead to metabolic changes and the production of oncometabolite 2-hydroxyglutarate (2HG). MR spectroscopy (MRS) can assess metabolic changes in disease states in-vivo and non-invasively. In this study, we demonstrate a validation pathway for two advanced MRS methods to be used as IDH-mutation biomarkers in clinic. METHOD Simulated, phantom, and healthy volunteer experiments were performed to optimise and validate three MRS sequences tuned for measuring 2HG. A PRESS sequence was used with TR/TE of 2500/97 ms aiming at the 2HG peaks around 2.25 ppm. An edited PRESS sequence, named MEGA-PRESS, tailored to 2HG 4.02 ppm peak was used with TR/TE of 3000/68 ms, 128 averages, and with editing pulses at 1.9 and 7.5 ppm. A long TE semi-LASER MRS sequence, with improved voxel localisation, was also used (TR/TE: 2500/110 ms). RESULTS Simulations were performed to find optimised sequence parameters and to develop basis sets for analysing the phantom and healthy volunteer acquisitions. Tumour-mimicking phantoms with variable concentrations of 2HG and cystathionine were created and validated with 800 MHz NMR spectroscopy. Phantoms were then used to assess the sensitivity and specificity of the MRS for 2HG and cystathionine. MEGA-PRESS proved Synthetic in-vivo 2HG spectra, combined from healthy volunteers and simulated or phantom-2HG spectra, were used to assess the spectral quality needed to reliably measure 2HG. CONCLUSION MEGA-PRESS proved to be the most robust MRS method and demonstrated accurate and precise measurement of phantom and synthetic 2HG with acceptable SNR. Clinical validation of the technique will need to be performed on LGG patient population, and the overall accuracy will be compared with patient IDH mutation status.

DESIGN AND SET UP OF A RANDOMISED CONTROLLED TRIAL OF MEDICINAL CANNABINOIDS IN RECURRENT GLIOBLASTOMA - THE ARISTOCRAT TRIAL

Abstract AIMS ARISTOCRAT is a unique, randomised, double-blind, placebo-controlled phase II trial of cannabinoids (nabixo- mols) alongside temozolomide in patients with MGMT-methylated recurrent GBM and is open to recruitment in 12 centres across the UK. It was rapidly funded through a crowdfunding campaign organised by The Brain Tumour Charity during the COVID-19 pandemic. METHOD This pragmatic phase II randomised trial was designed and set up by a multi-disciplinary team of co-applicants and trial management group (TMG) members comprising of clinicians, statisticians, trialists, Patient & Public Involvement (PPI), pharmacists and quality of life (QoL) researchers. The protocol randomises on a 2:1 ratio between nabiximols or matched placebo with standard dose temozolomide in patients at first recurrence of IDH wild-type GBM. Unique aspects include self-titration of nabiximols based on individual tolerance, and fully blinded randomisation with matched placebo. The primary outcome measure is overall survival time with key secondary outcomes including survival at 6, 12 and 24 months, progression-free survival time, health-related QoL and adverse events. Intermediate assessment of feasibility to confirm safety, compliance and achievability of recruitment will be undertaken after 40 patients are randomised. PPI input has been critical in the trial and patient-facing information design. RESULTS The trial has promoted a high level of patient and public interest, including press coverage. The trial aims to recruit a total of 234 patients over an 18 month period. CONCLUSION ARISTOCRAT will provide unique, robust clinical data on the role of nabiximols (combined with temozolomide) in improving overall survival and the impact on QoL for patients with recurrent GBM and is the first of its kind in cancer patients.

Exploring the role of ADAMTSL2 across multiple cancer types: A pan-cancer analysis and validated in colorectal cancer

BackgroundRecent studies have established a correlation between ADAMTSL2 (ADAMTS-like 2) and the development of various cancers. This study aims to conduct a comprehensive pan-cancer analysis in 37 cancer types and investigate its potential role in colon and rectal adenocarcinoma (COADREAD).MethodPan-cancer and mutation data were sourced from The Cancer Genome Atlas (TCGA) database and analyzed using Sangerbox analysis platform. We explored the expression patterns and prognostic implications of ADAMTSL2, and investigated its relationships with tumor heterogeneity, stemness, immune checkpoint genes, immune cell infiltration, RNA modifications, and mutational profiles across different cancers. Additionally, with Ethics Committee approval, we conducted immunohistochemical (IHC) analysis on 120 COADEAD samples to evaluate ADAMTSL2 expression and its association with clinicopathological parameters.ResultsADAMTSL2 expression was positively correlated with the hazard ratio of OS, DSS, DFI and PFI for ESCA and COADREAD. A negative correlation was observed between ADAMTSL2 expression and NEO levels in COAD. Gene alterations in ADAMTSL2 were observed, with a mutation frequency of 5.0% in COAD. There is a significant correlation between ADAMTSL2 expression and immune cell infiltration in a variety of cancers. The expression level of ADAMTSL2 protein was associated with T stage, N stage, M stage (p < 0.05). Kaplan‒Meier survival curves demonstrated that the high ADAMTSL2 group had a shorter OS time (p = 0.047) and progression free survival time (p = 0.026) than the low ADAMTSL2 group.ConclusionIn summary, we conducted a comprehensive pan-cancer analysis of ADAMTSL2 and we demonstrated that ADAMTSL2 may serve as a novel prognostic biomarker and immunotherapy target in COADREAD.

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.

Preoperative Serum Glycan Levels Reflect Progression of Patients With Hepatocellular Carcinoma.

Abnormal glycosylation is associated with tumors. The clinical value of serum glycans in assessing progression of hepatocellular carcinoma (HCC) patients remains a challenge. A study dynamically comparing levels of fifteen lectin-specific glycans between preoperative and postoperative serum of 65 HCC patients was conducted via lectin biochip technology. Multivariable logistic regression analysis was used to address associations between serum glycan levels and clinicopathological characteristics. Kaplan-Meier analysis was used to evaluate the impacts of serum glycan levels on overall survival (OS) and progression-free survival (PFS) of the HCC patients. HCC patients presented significantly higher levels of the lectin-specific glycans in preoperative serum than disease-free individuals (p < 0.001 - p = 0.029), except ConA. The glycans in preoperative sera were significantly related to tumor size, pTNM, metastasis, BCLC stage, portal hypertension (PHT), and platelet count (PLT), respectively (p < 0.05). Multivariate logistic analyses indicated that tumor size and pTNM independently impact on glycan-specific lectins either LTL, UEA-I, VVL, NPL, WGA, PNA, MAL-I, SNA, or PHA-L (p = 0.003 - p = 0.044); BCLC stage and PLT were independent factors influencing the serum glycans recognizable DSA (p = 0.024) and SNA (p = 0.050), respectively. Surgical excision of tumor mass significantly reduced glycan levels in sera. Tumor differentiation, albumin, and ABO type significantly revealed independent influence on glycan-specific lectins, such as RCA-I (p = 0.024), VVL (p = 0.024), and Con A (p = 0.026) in the postoperative serum. HCC patients with high levels of VVL-binding glycans significantly benefited from a longer OS time (p = 0.016, HR: 0.460, 95% CI: 0.237-0.892) and a better PFS time (p = 0.004; HR: 0.435, 95% CI: 0.237-0.799), respectively. Serum glycans could reflect surgical outcomes in at-risk patients and become valuable biomarkers in evaluating the progression of HCC patients.

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.

Efficacy of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in hepatocellular carcinoma with macrovascular invasion: a single-center retrospective analysis.

Objective The influence of macrovascular invasion on the therapeutic efficacy of Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) in hepatocellular carcinoma (HCC) patients has not been previously reported. This study primarily examines the therapeutic effect of ALPPS in treating HCC with macrovascular invasion. Methods 89 patients who underwent ALPPS at the First Affiliated Hospital of Guangxi Medical University from December 2016 to December 2021 were included. Patients were categorized into three groups based on macrovascular invasion status: pure HCC, HCC with portal vein tumor thrombus (PVTT), and HCC with hepatic vein tumor thrombus (HVTT). Outcome measures such as postoperative complications, liver hyperplasia rates, and survival times were compared across the groups. Results The study comprised 44 patients without macrovascular invasion and 45 cases with it, including 37 PVTT and 8 HVTT cases. Patients with PVTT or HVTT had a higher rate of complications and liver failure after the first ALPPS stage compared to those without macrovascular invasion (P = 0.018, P = 0.036). This trend was also observed in the stratified analysis of severe complications. However, no significant differences were found in these outcomes after the second ALPPS stage among the groups. The volume and rate of future liver remnant proliferation between the two stages of ALPPS were not statistically different among the groups, with median overall survival times of 42, 39, and 33 months, and progression-free survival times of 30, 24, and 14 months, respectively (P = 0.412 and P = 0.281). Conclusion ALPPS for HCC with macrovascular invasion was considered safe, feasible, and effective, as it achieved therapeutic effects comparable to those in cases without macrovascular invasion.

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.

Evaluation of immune checkpoint inhibitors for colorectal cancer: A network meta‑analysis.

Colorectal cancer (CRC) is challenging to treat due to its high metastatic rate. Recent strategies have focused on combining immune checkpoint inhibitors (ICIs) with other treatments. The aim of the present study was to conduct a network meta-analysis of randomized controlled trials (RCTs) to assess the efficacy and adverse effects of different ICI treatments for CRC. A literature search for RCTs was conducted using PubMed, the Cochrane Library, Embase, ClinicalTrials.gov and Web of Science databases, covering the period from the inception of each database until April 2024. A total of 12 RCTs involving 2,050 participants were selected for inclusion in the analysis. The network meta-analysis employed the MetaInsight tool to assess multiple endpoints. The criteria for study selection were based on the Population, Intervention, Comparison, Outcome and Studies framework as follows: i) Population, patients with CRC; ii) intervention, studies using ICI to treat CRC; iii) comparison, active comparators, including placebo; iv) outcome, overall survival, progression-free survival, objective response rate and adverse events; and v) study design, RCTs. The results of the analysis revealed that programmed cell death-ligand 1 (PD-L1) inhibitors significantly improved overall survival time [mean difference (MD), 2.28 months; 95% confidence interval (CI), 0.44 to 4.11], while programmed cell death protein 1 (PD-1) inhibitors exhibited a superior progression-free survival time (MD, 4.79 months; 95% CI, 3.18 to 6.40) compared with active comparators. However, none of the ICI treatments had significant differences in odds ratios for the objective response rate and adverse events compared with active comparators. These findings indicate that treatment with PD-L1 and PD-1 inhibitors improved the overall survival time and delayed disease progression in patients with CRC. These findings offer valuable insights for future research aimed at improving CRC patient outcomes.

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.

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.

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.

Vasculogenic mimicry triggers early recidivation and resistance to adjuvant therapy in esophageal cancer

ObjectiveTo investigate the impact of vasculogenic mimicry (VM) and postoperative adjuvant therapy on the prognosis and survival of patients with esophageal squamous cell carcinoma (ESCC), as well as to assess whether VM affects the clinical benefit of postoperative adjuvant therapy.MethodsThis single-center retrospective analysis included patients who underwent radical surgery for ESCC, which was documented in the medical record system. The presence or absence of VM in surgical specimens was determined using double staining with PAS/CD31. Stratification was applied based on adjuvant therapy and VM status. Survival curves and COX modeling were used to analyze the impact of the presence or absence of VM on the benefit of adjuvant therapy and the survival prognosis of patients.ResultsVM-positive patients were more prone to postoperative recurrence and metastasis. VM was identified as an independent risk factor for progression-free survival (PFS) (p < 0.001, 95% CI:1.809–3.852) and overall survival (OS) (p < 0.001, 95% CI:1.603–2.786) in postoperative ESCC. Postoperative adjuvant therapy significantly prolonged PFS (p = 0.008) and OS time (p < 0.001) in patients with stage II and III ESCC, with concurrent chemoradiotherapy being the most effective. However, the presence of VM significantly reduced the benefits of postoperative adjuvant therapy (p < 0.001).ConclusionVM negatively impacts the prognosis of postoperative ESCC patients and reduces the efficacy of postoperative adjuvant therapy.

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.

Relationship between TIGIT expression on T cells and the prognosis of patients with hepatocellular carcinoma

BackgroundTranscatheter arterial chemoembolization (TACE) combined with targeted therapy and immunotherapy can significantly improve the prognosis of patients with hepatocellular carcinoma (HCC). T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) is a novel immunosuppressive molecule. This study aimed to analyze the clinical correlation between TIGIT expression on T cells and patients with HCC.MethodsClinical data from 140 patients with HCC were retrospectively collected, and TIGIT expression on T cells was examined in each patient. Patients were subsequently divided into high- and low-expression groups, and their prognosis was analyzed.ResultsPatients with a high TIGIT expression on their T cells at baseline had a larger tumor volume, later staging, higher proportion of regulatory T cells, higher blood concentrations of interleukin (IL)-6 and IL-10, and lower interferon-γ concentrations. Following TACE, CD155 concentration decreased; however, TACE did not affect TIGIT expression on T cells. Additionally, among patients receiving TACE combined with apatinib and camrelizumab treatment, patients with a high TIGIT expression on T cells had significantly shorter progression-free survival (PFS) and overall survival times than those of patients in the low-expression group. Patients receiving TACE combined with apatinib and camrelizumab treatment with higher TIGIT expression have shorter PFS time than those receiving TACE combined with apatinib treatment.ConclusionsPatients with HCC that have a high TIGIT expression on their T cells exhibited poorer baseline characteristics, immunosuppressive status, and prognosis after receiving TACE combined with apatinib and camrelizumab and maybe more suited to receive TACE combined with apatinib treatment instead.

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.