Independent Prognostic Factor For Progression-free Survival Research Articles

Percutaneous vertebroplasty/kyphoplasty contributes to the improved outcome in patients with newly diagnosed multiple myeloma: A single center cohort study

ObjectiveTo evaluate the efficacy and prognosis of percutaneous vertebroplasty/kyphoplasty (PVP/PKP) in patients with newly diagnosed multiple myeloma (NDMM). MethodsClinical data of NDMM patients who underwent PVP/PKP during front-line regimen at Peking Union Medical College Hospital from January 1, 2003, to June 30, 2023, were analyzed. Patients with comparable bone diseases not receiving orthopedic surgery were selected as controls. Visual analogue scale (VAS) score, progression-free survival (PFS), and overall survival (OS) were compared. ResultsBaseline characteristics were matched between the surgical group (n = 51 with 56 surgeries) and non-surgical group (n = 102), including demographics, tumor load, International Staging System (ISS), bone diseases, cytogenetic abnormalities, first-line treatment, and autologous stem-cell transplantation (ASCT). Bone lesions for PVP/PKP were located at thoracic vertebrae (53.6 %, 30/56) or lumbosacral vertebrae (46.4 %, 26/56). The postoperative VAS score was significantly improved (2.25 ± 0.81 vs 5.92 ± 1.05, P < 0.001). The median follow-up time was 51[38–70] months. Kaplan-Meier survival analysis suggested that both PFS (37[17–89] vs 23[12–61] months, HR 0.648, 95 %CI 0.431–0.973, P = 0.047) and OS (not reached vs 66[28-NR] months, HR 0.519, 95 %CI 0.296–0.910, P = 0.045) were significantly prolonged in the surgical group. COX multivariate analysis suggested that PVP/PKP was an independent prognostic factor for PFS (P = 0.021, HR 0.589, 95 %CI 0.376–0.922) and OS (P = 0.038, HR 0.496, 95 %CI 0.255–0.963). Subgroup analysis confirmed that patients with ISS II/III or non-ASCT achieved better PFS and OS in the surgical group (PFS: P = 0.033, P = 0.040; OS: P = 0.024, P = 0.018 respectively), while similar survival outcome was observed in patients with ISS I or ASCT between two groups. ConclusionFor NDMM patients, not only does PVP/PKP alleviate bone pain, meanwhile, it improves the PFS and OS in advanced subpopulation or non-transplant myeloma patients, which suggests that shortening the gap from symptom onset to diagnosis by orthopedic surgery favors clinical prognosis.

The predictive value of delta-like3 and serum NSE in evaluating chemotherapy response and prognosis in patients with advanced small cell lung carcinoma: An observational study.

Lung cancer is one of the most malignant tumors with fastest morbidity and mortality. Small cell lung cancer (SCLC) is the most malignant pathological type of lung cancer with early metastasis and poor prognosis. At present, there is a lack of effective indicators to predict prognosis of SCLC patients. Delta-like 3 protein (DLL3) is selectively expressed on the surface of SCLC and is involved in proliferation and invasion. Neuron-specific enolase (NSE) is an enolase isoenzyme that is generally regarded as a biomarker for SCLC and may correlate with stage of SCLC, prognosis and chemotherapy response. NSE can be influenced by different types of factors. To explore the associations between expression levels of DLL3 in tumor tissues with platinum/etoposide chemotherapy response, and assess the prognostic values of DLL3, NSE and other potential prognostic factors in advanced SCLC patients were herein studied. Ninety-seven patients diagnosed with SCLC in Zhongda Hospital from 2014 to 2020 were enrolled in the study. Serum NSE levels were tested using ELISA methods before any treatment. The expression of DLL3 in tumor tissue was detected by Immunohistochemistry (IHC). We investigated the relationship of DLL3 expression with chemotherapy and survival. Progression free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Multivariate Cox-proportional hazard regression was used to identify predictors of PFS and OS. DLL3 was detected in 84.5% (82/97) of all patients' tumor samples by IHC, mainly located on the surface of SCLC cells. Lower DLL3 expression was associated with longer PFS and better chemotherapy response. OS had no significant differences. Multivariate analysis by Cox Hazard model showed that, high DLL3 expression and maximum tumor size >5 cm were independent risk factors for PFS, where NSE < 35 ng/mL and age < 70 were independent prognostic factors for OS. Early stage was independent prognostic factors for PFS and OS (P < .05 log-rank). DLL3 was expressed in the most of SCLCs. DLL3 expression level in the tumor and NSE level in the serum may be useful biomarkers to predict the prognosis of SCLC. DLL3 may be a potential therapeutic target for SCLC in the future.

Low Expression of GRIM-19 Correlates with Poor Prognosis in Patients with Upper Urinary Tract Urothelial Carcinoma

Purpose: This study aimed to clarify the expression of a gene associated with Retinoid- Interferon-Induced Mortality-19 (GRIM-19) in Upper Urinary Tract Urothelial Carcinoma (UUTUC) and its prognostic significance for UUTUC patients. Materials and Methods: Immunohistochemical (IHC) staining was used to determine the GRIM-19 expression in 70 paired samples. Progression-Free Survival (PFS) and Cancer-Specific Survival (CSS) were assessed using the Kaplan-Meier method. The independent prognostic factors for PFS and CSS were analyzed by multivariable Cox regression models. Results: IHC staining showed that GRIM-19 expression was significantly decreased in UUTUC, and its cellular location changed from being both cytoplasmic and nuclear to only cytoplasmic. Kaplan- Meier analysis revealed that the patients with tumors expressing low GRIM-19 had a significantly higher risk for tumor progression (P = 0.002) and cancer-specific mortality (P &lt; 0.001) compared to those with high GRIM-19 levels. The Cox regression showed that both GRIM-19 expression (P = 0.025) and lymph node metastasis (LN) (P = 0.007) were independent predictors of progression in the muscle-invasive (MIC) subgroup. GRIM-19 expressions (entire cohort: P = 0.011; MIC subgroup: P = 0.025), LN (entire cohort: P = 0.019; MIC subgroup: P = 0.007), and progression (entire cohort: P &lt; 0.001; MIC subgroup: P &lt; 0.001) were independent predictors of cancer-specific survival. Conclusion: Low expression of GRIM-19 in patients with UUTUC had significantly shorter PFS or CSS compared to those with high GRIM-19-expressing tumors. High GRIM-19 expression was also strongly associated with longer PFS in MIC patients. It indicates that GRIM-19 might serve as a promising prognostic biomarker for UUTUC patients.

A preliminary study on the timing of radiotherapy for chemoimmunotherapy in oligometastatic non-small-cell lung cancer with negative driver genes.

e20084 Background: Local radiotherapy (LRT) is reported to provide durable local and distant disease control for oligometastatic non-small cell lung cancer (NSCLC) in accumulating evidence, but research on the optimal initial time point remains scarce. We conducted a study to preliminarily evaluate the timing of radiotherapy for chemoimmunotherapy in Oligometastatic Non-small-cell lung cancer with negative driver genes. Methods: 50 patients diagnosed with Oligometastatic Non-small-cell lung cancer with negative driver genes who were treated with chemoimmunotherapy and radiotherapy were retrospectively recruited between January 2018 and October 2023. They were divided into two groups: one early to initiate radiotherapy group (≤2 cycles of immunotherapy, EAR group) and one deferred radiotherapy group (&gt;2 cycles of immunotherapy, DEF group). The clinical efficacy and adverse reactions were compared between the two groups. Progression-free survival (PFS) and overall survival (OS) were evaluated by Kaplan-Meier curves, the Cox proportional hazard model was used to find out predictors of PFS and OS. Results: The tumor control rates had no significance was observed when comparing these two groups (50.0% and 26.9%, respectively, p = 0.093). The PFS in the RAE group was significantly higher than that in the DEF group (median PFS: 12.2 months vs 5.3 months, P&lt;0.05). The OS in two groups were no significance (median OS: 20.5months vs 23.1months, P&gt;0.05). The results of the Cox multivariate regression analysis revealed that the number of metastatic lesions and organs were independent prognostic factors for PFS. The number of metastatic lesions and organs, maintain therapy were independent predictors associated with OS. All patients well tolerated the treatments. Conclusions: Early initiation of local radiotherapy resulted in better PFS and no significant increase in adverse reactions was observed.

PD-1 inhibitor combined with ablation in liver metastasis: A retrospective, multicenter study.

e14644 Background: This study aimed to retrospectively evaluate the efficacy of ablation combined with programmed cell death protein 1 (PD-1) inhibitor versus PD-1 inhibitor monotherapy in patients with liver metastasis. Methods: We retrospectively enrolled patients with liver metastasis who received PD-1 inhibitor therapy with or without ablation at three medical institutions between January 2017 and September 2022. Progression-free survival (PFS) and 1-year survival rates were compared after propensity score matching. Additionally, intrahepatic and extrahepatic lesion progression and treatment-related adverse events were recorded during follow-up. Finally, prognostic factors for the combined therapy group were analyzed. Results: We included 172 patients and classified them into the combined therapy and PD-1 inhibitor monotherapy (n = 86 each) groups. Patients in the combined therapy group had better median PFS and 1-year survival rates than those in the PD-1 inhibitor monotherapy group. Combined therapy was an independent prognostic factor for PFS in the univariate and multivariate analyses. New lesions constituted the main pattern of progression, with combined therapy showing significantly lower intrahepatic progression, but similar extrahepatic progression rates. Adverse events associated with PD-1 inhibitors were comparable between the two groups. Additionally, 8 (9.3%) patients experienced ablation-related complications. However, neither univariate, nor multivariate analyses revealed the predictive factors for PFS in the combined therapy group. Conclusions: Ablation combined with a PD-1 inhibitor was superior to PD-1 inhibitor monotherapy in improving the survival of patients with liver metastasis.

Single-center retrospective analysis of second-line treatment with regorafenib in patients with advanced colorectal cancer among the COVID-19 pandemic.

e15552 Background: Regorafenib targets multiple tyrosine kinases that has been approved for the third-line treatment in metastatic colorectal cancer (mCRC) patients in China. Here, We retrospectively analyzed the efficacy and safety of regorafenib alone or combined with chemotherapy/immunotherapy in the second-line treatment for those who cannot visit hospital for their chemotherapies because of the COVID-19 pandemic. Methods: Individual patient data from Peking University Third Hospital were analyzed retrospectively from January 2020 to September 2023. The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS) and safety. Results: The median age of 31 patients was 65 years, the median PFS was 6 months (1–21 months), and the median OS was 20 months (3–38 months). PFS tended to be prolonged with regorafenib plus capecitabine or immunotherapy in 12 subjects versus regorafenib alone in 19 subjects (8 months vs. 4 months, P = 0.306), with no statistical difference, and so did OS (27 months vs. 15 months, P = 0.899).The analysis of PFS (2.5 months vs. 7 months vs. 4 months, P = 0.164) and OS (13 months vs. 28 months vs. 20 months, p = 0.417) in patients with liver, lung, or abdominal/peritoneal metastases at the initiation of treatment demonstrated poor survival prognosis in patients with liver metastasis. Multivariate analysis showed that regorafenib combined with capecitabine or immunotherapy (wald = 5.766, p = 0.016) and non-liver metastasis (wald = 4.223, p = 0.040) were independent prognostic factors for PFS in the second-line treatment. Adverse drug reactions (ADRs) mainly included hand-foot skin reactions (HFSRs), fatigue, hypertension, and proteinuria, due to which 3 subjects discontinued the treatment. The incidence of Grade 3/4 ADRs was 19.3%, 16.9%, 12.9%, and 9.6%, respectively. Conclusions: Regorafenib alone or combined with chemotherapy/immunotherapy is safe and feasible in the second-line treatment for advanced colorectal cancer, and therefore further prospective studies can be conducted to explore combination therapies.

Immune checkpoint inhibitor retreatment in second-line treatment of esophageal cancer: A real-world study.

e16034 Background: Immunotherapy combined with chemotherapy has been recommended in several guidelines and consensus for the first-line treatment of advanced esophageal cancer(EC), but it is controversial whether to continue immune checkpoint inhibitors (ICIs) after the progress of first-line immunotherapy. Methods: This was a single-center, retrospective, observational, real-world study to collect general conditions and clinical data of EC patients hospitalized in the First Affiliated Hospital of Henan University of Science and Technology between February 2020 and December 2023. All patients received programmed cell death protein 1 (PD-1) or its ligand (PD-L1) inhibitor combination therapy in the first-line and received at least two cycles of PD-1/PD-L1 inhibitor-based therapy in the second-line setting after progression. We evaluated the efficacy and safety including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), grade 3-5 treatment-related adverse effects (TRAE) and immune-related adverse events (irAEs). We also evaluated the relationship between clinical features and outcomes using univariate and multivariate analyses. Results: We enrolled 214 patients, with a median age 67.9 (47 – 87) years, male sex 66.8%, 201(93.9%) ESCC and 11(5.1%) EAC. In all patients, the mOS and mPFS were 9.6 (95%CI 9.1-10.1) months and 4.4 (95%CI 4.1-4.7) months; The ORR was 33.2%, DCR was 65.9%. 162 (75.7%) patients treated with immunochemotherapy(I+C), 37 (17.3%) patients received immunotherapy combined with anti-angiogenic drugs(I+A) and 15 (7.0%) patients treated with immunotherapy combined with chemotherapy and anti-angiogenic drugs(I+C+A). The mOS were 9.1 (95% CI 8.4 – 9.8) months, 10.0 (95% CI 8.7 – 11.3) months and 11.5 (95% CI 10.7 – 12.3) months, respectively. The mPFS were 4.3m (95%CI 4.0-4.6) months, 4.3 (95%CI 4.0-14.6) months and 6.0 (95%CI 4.2-6.4) months. mPFS and mOS did not have significant difference between these groups. Univariate and multivariate analyses showed that PFS more than 6 months on first-line therapy was an independent prognostic factor for PFS and OS in second-line therapy. The incidence of grade ≥ 3 TRAEs and irAEs were 25.7% and 5.6%. No treatment-related deaths occurred. Conclusions: This real-world data showed PD-1 or PD-L1 inhibitors retreatment might have good efficacy and manageable safety in EC patients who progress after first-line immunochemotherapy. [Table: see text]

Association of a clinical model based on skeletal muscle radiation attenuation with efficacy for patients with gastric cancer treated with chemotherapy plus PD-1 antibodies: A single-center retrospective study.

e16029 Background: Biomarkers to select gastric cancer (GC) patients who can benefit from PD-1 antibody-based treatment are under investigation. We aimed to assess the association between body composition parameters and efficacy of chemotherapy plus PD-1 antibodies in GC patients. Methods: Clinical information of GC patients receiving perioperative chemotherapy with or without PD-1 antibodies was reviewed. Tumor regression grade (TRG) of gastric cancer was recorded after resection. Radiation attenuation and index of skeletal muscle, visceral adipose tissue and subcutaneous adipose tissue were calculated based on computed tomography (CT) images at the third lumbar (L3) level using SliceOmatic software. Associations between clinical parameters and patients’ outcomes including TRG, progression-free survival (PFS), and overall survival (OS) were analyzed. Results: A total of 120 patients treated with chemotherapy plus PD-1 antibodies (IO cohort) and 82 patients treated with chemotherapy alone (CTx cohort) were enrolled. TRG0/1 rates in the IO cohort and CTx cohort were 45.8% and 32.9%. High skeletal muscle radiation attenuation (SMRA), neutrophil to lymphocyte ratio (NLR) &lt; 2.65, and weight loss &lt; 5% were associated with TRG0/1 in the IO cohort but not in the CTx cohort. High SMRA was an independent prognostic factor of PFS in the IO cohort (HR = 0.333, 95%CI 0.115-0.970, P= 0.044). A clinical model based on SMRA, NLR and weight loss was established to stratify patients into 3 groups, including group 1: High SMRA with NLR &lt; 2.65 and weight loss &lt; 5%, group 2: High SMRA with NLR≥2.65 and/or weight loss≥5%, and group 3: Low SMRA. In the IO cohort, patients in group 1 showed higher TRG0/1 rate (n = 27/40, 67.5%, P&lt; 0.001) than group 2 (n = 26/63, 41.3%) and group 3 (n = 2/17, 11.8%). The clinical model was also associated with patients’ survival. Conclusions: A clinical model combining baseline SMRA, NLR and weight loss could identify well-responding GC patients treated with chemotherapy plus PD-1 antibodies.

Prognostic value of visual IMPeTUs criteria and metabolic tumor burden at baseline [18F]FDG PET/CT in patients with newly diagnosed multiple myeloma

Background2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography combined with low-dose computed tomography (PET/CT) can be used at diagnosis to identify myeloma-defining events and also provides prognostic factors. The aim of this study was to assess the prognostic significance of baseline [18F]FDG PET/CT visual IMPeTUs (Italian myeloma criteria for PET Use)-based parameters and/or total metabolic tumor volume (TMTV) in a single-center population of patients with newly diagnosed multiple myeloma (NDMM) eligible for transplantation.MethodsPatients with MM who underwent a baseline [18F]FDG PET/CT were retrospectively selected from a large internal database of the University Hospital of Liege (Liege, Belgium). Initially, all PET/CT images were visually analyzed using IMPeTUs criteria, followed by delineation of TMTV using a semi-automatic lesion delineation workflow, including [18F]FDG-positive MM focal lesions (FL) with an absolute SUV threshold set at 4.0. In a first step, to ensure PET/CT scans accurate reporting, the agreement between two nuclear medicine physicians with distinct experience was assessed. In the second step, univariable and multivariable analyses were conducted to determine the prognostic significance of [18F]FDG PET/CT parameters on progression free survival (PFS) and overall survival (OS), respectively.ResultsA total of 40 patients with NDMM were included in the study. The observers agreement in the analysis [18F]FDG PET/CT images was substantial for the presence of spine FL, extra spine FL, at least one fracture and paramedullary disease (Cohen’s kappa 0.79, 0.87, 0.75 and 0.64, respectively). For the presence of skull FL and extramedullary disease the agreement was moderate (Cohen’s kappa 0.56 and 0.53, respectively). Among [18F]FDG PET/CT parameters, a high number of delineated volumes of interest (VOI) using the SUV4.0 threshold was the only independent prognostic factor associated with PFS [HR (95% CI): 1.03 (1.004–1.05), P = 0.019] while a high number of FL (n > 10; F group 4) was the only independent prognostic factor associated with OS [HR (95% CI): 19.10 (1.90–191.95), P = 0.01].ConclusionOur work confirms the reproducibility IMPeTUs criteria. Furthermore, it demonstrates that a high number of FL (n > 10; IMPeTUs F group 4), reflecting a high [18F]FDG-avid tumor burden, is an independent prognostic factor for OS. The prognostic value of the TMTV delineated using a SUV4.0 threshold was not significant. Nevertheless, the count of delineated [18F]FDG-avid lesions VOI using a SUV4.0 threshold was an independent prognostic factor for PFS.

Characteristic features and prognostic factors in gastric cancer patients with bone metastases: multicenter experience

We evaluated the incidence, clinicopathological features, prognostic factors, progression-free survival (PFS) and overall survival (OS) of patients with gastric cancer and bone metastases. The medical records of 110 patients with bone metastases were retrospectively analyzed. In our study, the incidence of bone metastases was 3.2%. The median patient age was 60 years. A total of 68 (61.8%) patients exhibited synchronous metastases, and 42 (38.2%) patients developed metachronous metastases. Alkaline phosphatase (ALP) levels were high in 54 (49%) patients. At the median follow-up time of 9.8 months, median PFS and OS times were 4.7 and 6.3 months, respectively. The median interval from the diagnosis to bone metastases was 9.3 months. Univariate analysis showed that Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2, stage at diagnosis, time of metastases, number of metastases, presence of extraskeletal metastases, use of zoledronic acid treatment, palliative chemotherapy post-bone metastases and radiotherapy to bone metastases were significant prognostic indicators for PFS. Additionally, ECOG PS ≥2, stage at diagnosis, time of metastases, number of metastases, presence of extraskeletal metastases, zoledronic acid treatment, palliative chemotherapy post-bone metastases, and radiotherapy to bone metastases significantly influenced OS. Moreover, in multivariate analysis, ECOG PS, time of metastases, presence of extra-bone metastases, and the use of palliative chemotherapy after bone metastases were found to be independent prognostic factors for PFS. Moreover, ECOG PS, time of metastases, and use of palliative chemotherapy after bone metastases were significantly independent prognostic indicators for OS. Our findings show that the presence of synchronous metastases, use of palliative chemotherapy, use of zoledronic acid after bone metastases, and ALP level within the normal range were significantly associated with prolonged OS in gastric cancer patients with bone metastases.

Intratumoral metabolic heterogeneity by 18F-FDG PET/CT to predict prognosis for patients with thymic epithelial tumors.

The aim of the present study was to evaluate the impact of intratumoral metabolic heterogeneity and quantitative 18F-FDG PET/CT imaging parameters in predicting patient outcomes in thymic epithelial tumors (TETs). This retrospective study included 100 patients diagnosed with TETs who underwent pretreatment 18F-FDG PET/CT. The maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on PET/CT were measured. Heterogeneity index-1 (HI-1; standard deviation [SD] divided by SUVmean) and heterogeneity index-2 (HI-2; linear regression slopes of the MTV according with different SUV thresholds), were evaluated as heterogeneity indices. Associations between these parameters and patient survival outcomes were analyzed. The univariate analysis showed that Masaoka stage, TNM stage, WHO classification, SUVmax, SUVmean, TLG, and HI-1 were significant prognostic factors for progression-free survival (PFS), while MTV, HI-2, age, gender, presence of myasthenia gravis, and maximum tumor diameter were not. Subsequently, multivariate analyses showed that HI-1 (p < 0.001) and TNM stage (p = 0.002) were independent prognostic factors for PFS. For the overall survival analysis, TNM stage, WHO classification, SUVmax, and HI-1 were significant prognostic factors in the univariate analysis, while TNM stage remained an independent prognostic factor in multivariate analyses (p = 0.024). The Kaplan Meier survival analyses showed worse prognoses for patients with TNM stages III and IV and HI-1 ≥ 0.16 compared to those with stages I and II and HI-1 < 0.16 (log-rank p < 0.001). HI-1 and TNM stage were independent prognostic factors for progression-free survival in TETs. HI-1 generated from baseline 18F-FDG PET/CT might be promising to identify patients with poor prognosis.

Efficacy and safety of hepatic arterial infusion chemotherapy combined with lenvatinib and PD-1 inhibitors for advanced hepatocellular carcinoma with macrovascular invasion

Background and aimsThe prognosis of hepatocellular carcinoma (HCC) with macrovascular invasion(MaVI)is poor, and the treatment is limited. This study aims to explore the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC), combined with lenvatinib and programmed cell death-1(PD-1) inhibitor in the first-line treatment of HCC with MaVI.MethodsFrom July 2020 to February 2022, we retrospectively analyzed consecutive patients with HCC with MaVI who received hepatic arterial infusion FOLFOX(oxaliplatin, 5-fluorouracil, and leucovorin)combined with lenvatinib and PD-1 inhibitor. The efficacy was evaluated by RECIST 1.1. Kaplan-Meier was used to explore the overall survival and progression-free survival (PFS), and the COX regression model was used to analyze the risk factors of PFS. Adverse events (AEs) were evaluated according to CTCAE5.0.ResultsThirty-two patients with HCC complicated with MaVI were recruited from the Second Affiliated Hospital of Nanchang University. Among the patients treated with HAIC combined with lenvatinib and PD-1 inhibitor, ten patients (31.25%) got partial response, eighteen patients (56.25%) maintained stable disease and four patients (12.50%) suffered progressive disease during follow-up; and objective response rate was 31.25%, and disease control rate was 87.5%. The median PFS was 179 days. Univariate and multivariate Cox analysis showed that the extrahepatic metastases and Child-Pugh score were independent prognostic factors of PFS. Twenty-two (68.75%) patients suffered adverse reactions. The main AEs were elevated transaminase (46.87%), thrombocytopenia (40.63%), hypoalbuminemia (28.13%), nausea and vomiting (21.88%), leukopenia (18.76%), abdominal pain (15.63%), hypertension (15.63%) and fever (15.63%). There were seven cases (21.88%) that had grade 3 or above AEs; Among them, two cases with elevated transaminase (6.25%), leukopenia, thrombocytopenia, nausea and vomiting, abdominal pain, and diarrhea occurred in one case respectively. Moreover, no treatment-related death was observed.ConclusionsHepatic arterial infusion of FOLFOX combined with lenvatinib and PD-1 inhibitor as the first-line treatment for HCC complicated with MaVI is effective, and adverse reactions are tolerable.

The Efficacy and Safety of Inetetamab and Pyrotinib in Combination with Vinorelbine for Second-line Therapy and Beyond in HER2-positive Metastatic Breast Cancer: A Single-institution Clinical Experience.

This study aimed to observe the efficacy and safety of inetetamab and pyrotinib in combination with vinorelbine in second-line therapy and beyond in HER2-positive metastatic breast cancer (MBC). Patients with HER2-positive MBC admitted to our hospital from January 2016 to December 2021 were selected. For patients who could not receive antibody‒drug conjugates (ADCs) during second-line (2nd-line) or third-line and beyond (≥ 3rd-line) anti-HER2 therapy, inetetamab + pyrotinib + vinorelbine was used for treatment until unacceptable adverse events occurred or the disease progressed, as evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 every 2 cycles. The progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), and adverse reactions were recorded. Multivariate Cox regression analysis was performed to explore the prognostic factors influencing the curative effect. Overall, 52 patients were included; 13 patients received 2nd-line treatment, and 39 patients received ≥ 3rd-line treatment. The median PFS (mPFS) for all patients treated with inetetamab + pyrotinib + vinorelbine was 7 months. The mPFS of the 2nd-line subgroup was significantly better than that of the ≥ 3rd-line subgroup (17 vs. 5 months, P = 0.001). The mPFS of the subgroups that received trastuzumab (H) or trastuzumab and pertuzumab (HP) only was significantly better than that of the H or HP and tyrosine kinase inhibitor (TKI) subgroups (8 vs. 5 months, P = 0.030). The mPFS of the HER2 resistance subgroup was better than that of the HER2 refractoriness subgroup (14 vs. 7 months, P = 0.025). Cox regression analysis showed that the treatment line (2nd-line more so than ≥ 3rd-line) was an independent prognostic factor for PFS. In addition, the ORR and CBR of 2nd-line patients were significantly higher than those of ≥ 3rd-line patients (69.2% vs. 30.8% and 92.3% vs. 64.1%, respectively). The most common hematological toxicities were leukopenia and neutropenia, and the most common nonhematological toxicity was diarrhea. Inetetamab and pyrotinib in combination with vinorelbine have good efficacy in ≥ 2nd-line treatment of HER2-positive MBC with controllable toxicity, and the combination is a new treatment option, especially for patients who cannot use ADCs in 2nd-line treatment.

Clinical outcomes of pomalidomide-based and daratumumab-based therapies in patients with relapsed/refractory multiple myeloma: A real-world cohort study in China.

Comparative investigations evaluating the efficacy of pomalidomide-based (Pom-based) versus daratumumab-based (Dara-based) therapies in patients with relapsed/refractory multiple myeloma (RRMM) remain scarce, both in randomized controlled trials and real-world studies. This retrospective cohort study included 140 RRMM patients treated with Pom-based or Dara-based or a combination of pomalidomide and daratumumab (DPd) regimens in a Chinese tertiary hospital between December 2018 and July 2023. The overall response rates (ORR) for Pom-based (n = 48), Dara-based (n = 68), and DPd (n = 24) groups were 57.8%, 84.6%, and 75.0%, respectively (p = 0.007). At data cutoff on August 1, 2023, the median progression-free survival (PFS) was 5.7 months (95% CI: 5.0-6.5) for the Pom-based group, 10.5 months (5.2-15.8) for the Dara-based group, and 6.7 months (4.0-9.3) for the DPd group (p = 0.056). Multivariate analysis identified treatment regimens (Dara-based vs. Pom-based, DPd vs. Pom-based) and Eastern Cooperative Oncology Group performance status (ECOG PS) as independent prognostic factors for PFS. In the subgroups of patients aged >65 years, with ECOG PS ≥2, lines of therapy ≥2, extramedullary disease or double-refractory disease (refractory to both lenalidomide and proteasome inhibitors), the superiority of Dara-based regimens over Pom-based regimens was not evident. A higher incidence of infections was observed in patients receiving Dara-based and DPd regimens (Pom-based 39.6% vs. Dara-based 64.7% vs. DPd 70.8%, p = 0.009). In real-world settings, Pom-based, Dara-based, and DPd therapies exhibited favorable efficacy in patients with RRMM. Dara-based therapy yielded superior clinical response and PFS compared to Pom-based therapy.

Drug-eluting beads transcatheter arterial chemoembolization combined with systemic therapy versus systemic therapy alone as first-line treatment for unresectable colorectal liver metastases.

The purpose of this retrospective study was to compare the therapeutic efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) combined with systemic therapy to systemic therapy alone as first-line treatment for unresectable patients with colorectal liver metastases (CRLM). From December 2017 to December 2022, patients with unresectable CRLM who received systemic therapy with or without DEB-TACE as first-line treatment were included in the study. The primary endpoint was progression-free survival (PFS). Secondary endpoints were tumor response, conversion rate and adverse events. Ninety-eight patients were enrolled in this study, including 46 patients who received systemic therapy combined with DEB-TACE (DEB-TACE group) and 52 patients who received systemic therapy alone (control group). The median PFS was elevated in the DEB-TACE group compared with the control group (12.1 months vs 8.4 months, p = 0.008). The disease control rate was increased in the DEB-TACE group compared with the control group (87.0% vs 67.3%, p = 0.022). Overall response rates (39.1% vs 25.0%; p = 0.133) and conversion rate to liver resection (33.8% vs 25.0%; p = 0.290) were no different between the two groups. The multivariate analysis showed that treatment options, size of liver metastasis, number of liver metastasis, synchronous metastases, and extrahepatic metastases were independent prognostic factor of PFS. Further subgroup analyses illustrated that PFS was beneficial with the DEB-TACE group in patients with age ≥ 60, male, left colon, synchronous metastases, bilobar, number of liver metastasis > 5, extrahepatic metastases, non-extrahepatic metastases, CEA level < 5 (ng/ml), and KRAS wild-type. No grade 4 or 5 toxicities related to DEB-TACE procedures were observed. In patients with unresectable CRLM, systemic chemotherapy with DEB-TACE as first-line treatment may improve progression-free survival and disease control rate outcomes over systemic chemotherapy alone with manageable safety profile.

The Roles of AGTRAP, ALKBH3, DIVERSIN, NEDD8 and RRM1 in Glioblastoma Pathophysiology and Prognosis.

This study determined the expression of five novel biomarker candidates in IDH wild-type glioblastoma (GBM) tissues compared to non-malign brain parenchyma, as well as their prognostic relevance for the GBM patients' outcomes. The markers were analysed by immunohistochemistry in tumour tissues (n = 186) and healthy brain tissues (n = 54). The association with the patients' overall survival (OS) and progression-free survival (PFS) was assessed by Kaplan-Meier and log-rank test. The prognostic value of the markers was determined using multivariate Cox proportional hazard models. AGTRAP, DIVERSIN, cytoplasmic NEDD8 (NEDD8c) and RRM1 were significantly overexpressed in tumour tissues compared to the healthy brain, while the opposite was observed for ALKBH3. AGTRAP, ALKBH3, NEDD8c and RRM1 were significantly associated with OS in univariate analysis. AGTRAP and RRM1 were also independent prognostic factors for OS in multivariate analysis. For PFS, only AGTRAP and NEDD8c reached significance in univariate analysis. Additionally, AGTRAP was an independent prognostic factor for PFS in multivariate models. Finally, combined analysis of the markers enhanced their prognostic accuracy. The combination AGTRAP/ALKBH3 had the strongest prognostic value for the OS of GBM patients. These findings contribute to a better understanding of the GBM pathophysiology and may help identify novel therapeutic targets in this type of cancer.

Chemotherapy versus chemotherapy plus immune checkpoint inhibitors for the first-line treatment of unresectable thymic carcinoma: A multicenter retrospective study.

Thymic carcinoma (TC) is a rare malignant tumor with a poor prognosis, and there is currently limited data on the use of immunotherapy in patients with unresectable TC. In this study, data of patients with unresectable TC diagnosed from January 2017 were retrospectively collected from multiple centers. Treatment response, progression-free survival (PFS), overall survival (OS), survival-independent prognostic factor, and adverse events (AEs) were further analyzed. As a result, a total of 93 patients with unresectable TC were enrolled, of which 54 received first-line chemotherapy, and 39 received chemotherapy plus immune checkpoint inhibitors (ICIs). The objective response rate was 50% (27/54) in the chemotherapy group and 76.9% (30/39) in the chemotherapy plus ICIs group. The chemotherapy plus ICIs group achieved significant median PFS benefit (8.8 vs. 34.9 months, p < .001) and median OS benefit (41.8 months vs. not reached, p = .025). Multivariate analysis showed that ICIs and local therapy were independent prognostic factors for PFS. In addition, 17 patients developed immune-related AEs (IRAEs), of which 15 (38.5%) had Grade 1 or 2 IRAEs and 2 (5.1%) had Grade 3 IRAEs in the chemotherapy plus ICIs group. In conclusion, the efficacy of chemotherapy plus ICIs is superior to chemotherapy, and the adverse effects are manageable in patients with unresectable TC.

Loss of methylthioadenosine phosphorylase immunoreactivity correlates with poor prognosis and elevated uptake of 11C-methionine in IDH-mutant astrocytoma.

The proximate localization of MTAP, which encodes methylthioadenosine phosphorylase, and CDKN2A/B on Chromosome 9q21 has allowed the loss of MTAP expression as a surrogate for homozygous deletion of CDKN2A/B. This study aimed to determine whether MTAP status correlates with clinical outcomes and 11C-methionine uptake in astrocytomas with IDH mutations. We conducted immunohistochemistry for MTAP in 30 patients with astrocytoma, IDH-mutant who underwent 11C-methionine positron emission tomography scans prior to surgical resection. The tumor-to-normal (T/N) ratio of 11C-methionine uptake was calculated using the mean standardized uptake value (SUV) for tumor and normal brain tissues. Cox regression analysis was used for multivariate survival analysis. Among IDH-mutant astrocytomas, 26.7% (8/30) exhibited the loss of cytoplasmic MTAP expression, whereas 73.3% (22/30) tumors retained MTAP expression. The median progression-free survival (PFS) was significantly shorter in patients with MTAP loss than those with MTAP retention (1.88years vs. 6.80years, p = 0.003). The median overall survival (OS) was also shorter in patients with MTAP loss than in MTAP-retaining counterparts (5.23years vs. 10.69years, p = 0.019). Multivariate analysis identified MTAP status (hazard ratio (HR), 0.081) and extent of resection (HR, 0.104) as independent prognostic factors for PFS. Astrocytomas lacking cytoplasmic MTAP expression showed a significantly higher median T/N ratio for 11C-methionine uptake than tumors retaining MTAP (2.12 vs. 1.65, p = 0.012). Our study revealed that the loss of MTAP expression correlates with poor prognosis and an elevated T/N ratio of 11C-methionine uptake in astrocytoma, IDH-mutant.

Metabolic Tumor Volume as Significant Predictor for Chemotherapy Containing PD-L1 Blocker in Extensive Stage Small Cell Lung Cancer.

Chemo-immunotherapy, including the programmed death ligand 1 (PD-L1) antibody, is an effective treatment for patients with extensive-stage small-cell lung cancer (ES-SCLC). However, no biomarker has been established for the prediction of chemo-immunotherapy. Therefore, we investigated the potential of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) as a predictive marker. Forty-six patients with ES-SCLC who received 18F-FDG-PET immediately before combined platinum-based chemotherapy with PD-L1 blockade as a first-line treatment were eligible, and the maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on 18F-FDG uptake were evaluated. PD-L1 and tumor infiltrative lymphocytes (TILs) were immunohistochemically analyzed in 36 of the 46 patients. A high MTV was significantly associated with poor performance status and low albumin levels, and there was a significant association between low albumin and high TLG. Univariate analysis identified sex, Brinkman index, and MTV as significant predictors of progression-free survival (PFS), and sex, SUVmax, MTV, and TLG as significant factors of overall survival (OS). Multivariate analysis revealed that sex, Brinkman index, and MTV were independent prognostic factors for PFS, and sex, SUVmax, MTV, and TLG were significant predictors of OS. SUVmax was significantly higher in patients with positive PD-L1 expression than in those with negative expression but was not significantly different between positive and negative TILs. Moreover, the levels of MTV and TLG were not closely associated with the levels of PD-L1 and TILs. MTV or TLG metabolic tumor activity is suitable for the prediction of chemo-immunotherapy outcomes in patients with ES-SCLC.

Soluble Immune Checkpoint Molecules as Predictors of Efficacy in Immuno-Oncology Combination Therapy in Advanced Renal Cell Carcinoma.

Immuno-oncology (IO) combination therapy is the first-line treatment for advanced renal cell carcinoma (RCC). However, biomarkers for predicting the response to IO combination therapy are lacking. Here, we investigated the association between the expression of soluble immune checkpoint molecules and the therapeutic efficacy of IO combination therapy in advanced RCC. The expression of soluble programmed cell death-1 (sPD-1), soluble programmed cell death ligand-1 (sPD-L1), soluble PD-L2 (sPD-L2), and lymphocyte activation gene-3 (sLAG-3) was assessed in plasma samples from 42 patients with advanced RCC who received first-line IO combination therapy. All IMDC risk classifications were represented among the patients, including 14.3, 57.1, and 28.6% with favorable, intermediate, and poor risk, respectively. Univariate analysis revealed that prior nephrectomy, sPD-L2 levels, and sLAG-3 levels were significant factors affecting progression-free survival (PFS), whereas multivariate analyses suggested that sPD-L2 and sLAG-3 levels were independent prognostic factors for PFS. In a univariate analysis of the overall survival, prior nephrectomy and sPD-L2 levels were significant factors; no significant differences were observed in the multivariate analysis. No significant correlation was observed between the sPD-L2 and sLAG-3 levels and PD-L2 and LAG-3 expression via immunohistochemistry. In conclusion, sPD-L2 and sLAG-3 expression may serve as a potential biomarker for predicting IO combination therapy efficacy.