Median Overall Survival For Patients Research Articles

Updated Survival Follow-Up for Phase Ib Trial of the Histone Deacetylase Inhibitor Abexinostat With Pazopanib in Patients With Solid Tumor Malignancies

PURPOSE Histone deacetylase (HDAC) inhibition downregulates hypoxia-inducible factor-1α and modulates multiple metabolomic pathways relevant in cancer. Here we report a potential novel biomarker to predict exceptional responders (>3 years) in patients receiving HDAC and vascular endothelial growth factor (VEGF) inhibition. PATIENTS AND METHODS Patients with solid tumor malignancies were enrolled in this phase Ib trial of abexinostat (4/7 ×21 days) and pazopanib (28/28 days), with a dose expansion in renal cell carcinoma (RCC). Plasma was analyzed for metabolomics and peripheral blood mononuclear cells (PBMCs) for VEGF and HDAC2 expression levels. RESULTS Fifty-one patients were enrolled: n = 36 patients in dose escalation and n = 15 in dose expansion. After the initial report in 2017, six patients had remained on study: four with RCC and one each with medullary thyroid and thymic neuroendocrine carcinoma. One patient with RCC remains on treatment for >11 years after progression on five systemic therapies. Overall, the median duration of therapy measured 5.6 (1-133) months. The median duration of therapy in exceptional responders measured 44.1 (39.8-133+) months. The median overall survival in patients with high PBMC HDAC2 expression versus low HDAC2 was 32.3 versus 9.2 months ( P = .004) for all patients and 43.3 versus 25.1 months for patients with RCC ( P = .09). Exceptional responders had lower kynurenine levels both pre- and post-treatment ( P = .002, P < .001, respectively). HDAC2 and kynurenine expression levels were inversely correlated ( P = .02). CONCLUSION Abexinostat added to pazopanib shows extended tolerability and long-term responses and survival. PBMC HDAC2 levels, the abexinostat target, are relevant predictors of response. In addition, metabolomic assessment points to kynurenine as a predictor for exceptional response to combined VEGF plus HDAC inhibition.

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

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

All-trans retinoic acid-mediated ADAR1 degradation synergizes with PD-1 blockade to suppress pancreatic cancer.

As a double-stranded RNA-editing enzyme and an interferon-stimulated gene, double-stranded RNA-specific adenosine deaminase (ADAR1) suppresses interferon signaling and contributes to immunotherapy resistance. Suppression of ADAR1 overcomes immunotherapy resistance in preclinical models, but has not yet been translated to clinical settings. By conducting a screening of a subset of the FDA-approved drugs, we found that all-trans retinoic acid (ATRA, also known as tretinoin) caused ADAR1 protein degradation through ubiquitin-proteasome pathways and concomitantly increased PD-L1 expression in pancreatic and breast cancers. In addition, the combination of ATRA and PD-1 blockade reprogrammed the tumor microenvironment and unleashed antitumor immunity and thereby impeded tumor growth in pancreatic cancer mouse models. In a pilot clinical trial, a higher dose of ATRA plus the anti-PD-1 antibody nivolumab prolonged median overall survival in patients with chemotherapy-resistant pancreatic cancer compared to a lower dose of the same regimen. In this study, ATRA was the first drug to be found to cause ADAR1 degradation. We propose translation of a promising 2-pronged antitumor strategy using ATRA and nivolumab to convert immunologically "cold" into "hot" tumors susceptible to immune checkpoint blockade.

Favorable Prognosis in Patients With Multiple Myeloma and Lenalidomide-Induced Skin Rash: A Multicenter Retrospective Study.

Although lenalidomide is an essential treatment for multiple myeloma (MM), skin rashes are a common adverse event. This retrospective study aimed to examine the association between skin rash development during lenalidomide treatment and the prognosis of relapsed/refractory MM. All patients who received lenalidomide at 10 hospitals between July 2009 and December 2015 were included in the study. The relationship of skin rash development with disease progression and survival was evaluated. Multivariate analysis was performed to identify factors affecting disease progression or survival, including skin rash. Of the 245 patients analyzed, 70 developed skin rashes. The median progression-free survival (PFS) of patients with skin rashes was 22.4 months, whereas the median PFS for patients who did not develop skin rashes was 10.5 months (p = 0.003). The median overall survival for patients with and without skin rash was 42.6 and 24.6 months, respectively (p = 0.013). Multivariate regression analysis showed that skin rash was an independent prognostic factor for PFS (p = 0.009). In this study, patients with skin rashes during lenalidomide treatment had significantly better PFS than those without such symptoms, indicating that lenalidomide-associated skin rashes may be a predictor of clinical outcomes in patients with MM.

ROR1 MRNA EXPRESSION IN GLIOMA - A NOVEL PROGNOSTIC BIOMARKER

Abstract AIMS Glioblastoma is the most common and aggressive primary brain tumour in adults. Despite maximal surgical resection followed by concomitant chemo-/radiotherapy, the three-year survival remains less than 5%. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) overexpression is associated with poor prognosis in several cancers. ROR1 therapeutics are in Phase I/II clinical trials making it an exciting novel target with translational potential to explore for glioblastoma treatment. The aim of this study was to examine the association between ROR1 mRNA expression and overall survival (OS), by applying the WHO 2021 classification of transcriptomic glioma datasets. METHOD Clinical, histological, and molecular data were extracted from four independent glioma datasets (TCGA, CGGA, Rembrandt, and Gravendeel) via the GlioVis portal and analysed using the WHO 2021 classification. Only confirmed cases of astrocytoma, oligodendroglioma, or glioblastoma, and ROR1 mRNA expression data were included (2,216 cases). Kaplan-Meier survival curves were produced for OS with low/high grade glioma versus ROR1 mRNA expression. Log-rank (Mantel-Cox) multivariate regression was applied to analyse the effect of selected covariates on OS and ROR1 mRNA expression. RESULTS We observed a significant decrease in median OS in patients with high-ROR1 mRNA expression when compared to the low-ROR1 mRNA expression cohort (20 and 70 months, respectively). High-grade gliomas represented the highest ROR1 mRNA expression across the consortium, resulting in a poor median OS of 16 months. CONCLUSION This study represents the first report of an association between OS and the oncogenic role of ROR1 in glioma, a targetable cell surface marker for novel putative treatment in glioblastoma.

Prognostic value of [18F]FDG PET/CT in metastatic hormone-sensitive prostate cancer at initial diagnosis: a retrospective cohort study

Introduction This retrospective study aimed to evaluate the prognostic value of [18F]FDG parameters in patients with visceral and bone metastatic hormone-sensitive prostate cancer (mHSPC). Patients and methods This analysis included the mHSPC patients who underwent [18F]FDG PET/CT at the initial diagnosis. Baseline characteristics were analyzed, and the uptake of [18F]FDG was quantified using SUVmax. Kaplan–Meier and Cox proportional hazard regression analysis were employed to evaluate the correlation between SUVmax and patient survival. Results Among the 267 patients enrolled, 90 (33.7%) presented with visceral metastases and 177 (66.3%) had bone metastases. The median follow-up for the visceral metastasis group was 35.5 months (IQR 26–53.8 months). The median overall survival for patients with lung, liver, or both metastases were 30, 21 and 17 months, respectively. Patients exhibiting higher [18F]FDG uptake in metastatic lesions experienced shorter overall survival (OS) in comparison to those with lower [18F]FDG uptake, both in the visceral metastases group (17 vs. 31 months, p = 0.002) and the bone metastases group (27.5 vs. 34.5 months, p < 0.001). Cox regression analysis further revealed that increased [18F]FDG uptake in metastatic lesions emerged as a significant risk factor in both OS and progression-free survival (PFS). In contrast, the variability in [18F]FDG uptake in primary lesions did not provide a reliable indicator for predicting prognosis. Conclusions In mHSPC patients, higher [18F]FDG uptake in metastatic lesions indicates shorter survival and increased risk of disease progression. The [18F]FDG SUVmax in primary tumors did not show significant prognostic value. Our study underscores the unique prognostic potential of [18F]FDG PET/CT in mHSPC patients, highlighting its importance in the management of both bone and visceral metastases.

Prognostic risk score and index including the platelet-to-lymphocyte ratio and lactate dehydrogenase in patients with metastatic or unresectable urothelial carcinoma treated with immune checkpoint inhibitors.

Avelumab and pembrolizumab are administered after platinum-based chemotherapy for the treatment of metastatic urothelial carcinoma. We explored the prognostic factors and risk scores for predicting the outcomes of metastatic or unresectable urothelial carcinoma at the start of treatment with immune checkpoint inhibitors. This retrospective study included patients with metastatic or unresectable urothelial carcinoma treated with avelumab or pembrolizumab after platinum-based chemotherapy between January 2017 and December 2022. Prognostic factors, including patient and tumor characteristics and blood data at the initiation of immune checkpoint inhibitor therapy, were examined. This study included 36 and 207 patients treated with avelumab and pembrolizumab, respectively, for metastatic or unresectable urothelial carcinoma. Eastern Cooperative Oncology Group performance status, presence of visceral metastases, platelet-to-lymphocyte ratio and lactate dehydrogenase levels were independent prognostic factors for predicting overall survival. The median overall survival of patients in the risk-score model was 58.5months (score zero), 27.9months (one), 13.1months (two) and 3.9months (three or higher). The C-index for overall survival was 0.718 for the newly developed risk score compared with 0.679 for the Bellmunt score and 0.703 for the Bellmunt-C-reactive protein score. Additionally, the C-index for overall survival using the immune prognostic index derived from lactate dehydrogenase and the platelet-to-lymphocyte ratio was 0.646 compared with 0.615 for the Lung Immune Prognostic Index. A risk score that includes the platelet-to-lymphocyte ratio and lactate dehydrogenase may serve as a useful model for predicting prognosis following the initiation of immune checkpoint inhibitors in patients with metastatic or unresectable urothelial carcinoma.

A weekly low-dose regimen of decitabine and venetoclax is efficacious and less myelotoxic in a racially diverse cohort

AbstractA metronomic, low-dose schedule of decitabine and venetoclax was safe and effective in myeloid malignancies with few dose reductions or interruptions in an older diverse population. Median overall survival for patients with acute myeloid leukemia and a TP53-mutation was 16.1 and 11.3 months, respectively. This trial was registered at www.clinicaltrials.gov as #NCT05184842.

Clinicopathological Features and Outcomes of Perioperative Treatment for Small Cell Carcinoma of the Bladder

Small cell carcinoma of the bladder (SCCB) is a rare malignant tumor of the bladder. This study aims to explore its clinicopathological features and prognostic factors and to explore the role of perioperative treatment methods. The clinical data of SCCB patients admitted to West China Hospital, Sichuan University over 8 years from January 2016 to January 2024 were collected. The clinicopathological features of SCCB were summarized. The survival outcomes and prognostic factors were analyzed. The effect of perioperative treatment on the improvement in prognosis was explored. A total of 31 confirmed cases of SCCB were enrolled. We observed a number of clinicopathologic features. All cases had advanced clinical staging, with the T staging status being above T2 in all cases, and distant metastasis was found in 23% of the newly diagnosed cases. A high proportion of the SCCB cases were combined with other histologic types, with 96% showing combination with urothelial carcinoma (UC). The SCCB patients had a poor prognosis, presenting a median survival of 12 months, 1-year overall survival (OS) of 57.9%, and 3-year OS of 27.6%. Patients with extensive-stage SCCB had a significantly worse prognosis than those with limited-stage SCCB did (median OS time of 17.0 months vs. 4.4 months, P<0.05). In limited-stage SCCB, the median OS of patients who underwent radical cystectomy (RC) was 19.9 months, while that of the patients who did not undergo RC was 15.2 months (P<0.05). The OS of patients who received perioperative therapy in combination with RC had longer OS than those who received only RC did (P<0.05). Among these, patients recevied neoadjuvant therapy (NAT) had a significantly longer OS than patients who didn't receive NAT (P<0.05). Subgroup analysis revealed that patients who were responsive to neoadjuvant therapy had longer disease-free survival and longer OS than those who were not responsive did (P<0.05). Lymph node metastasis was an independent factor of poor prognosis (hazard ratio [HR]=15.21, 95% confidence interval [CI]: 1.732-133.912, P=0.014). NAT prior to RS was an independent protective factor, significantly reducing the risk of death compared with RC alone (HR=0.03, 95% CI: 0.001-0.724, P=0.031). RC is an effective treatment that prolongs the survival of patients with limited-stage SCCB. RS combined with NAT can further improve their survival.

Retrospective analysis of patients with hepatocellular carcinoma complicated with human immunodeficiency virus infection after hepatectomy.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide, with a 5-year relative survival rate of approximately 18%. The similarity between incidence and mortality (830000 deaths per year) underscores the bleak prognosis associated with the disease. HCC is the fourth most common malignancy and the second leading cause of cancer death in China. Most patients with HCC have a history of chronic liver disease such as chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, alcoholism or alcoholic steatohepatitis, nonalcoholic fatty liver disease, or nonalcoholic steatohepatitis. Early diagnosis and effective treatment are the keys to improving the prognosis of patients with HCC. Although the total number of human immunodeficiency virus (HIV)-infected patients is declining globally the incidence of HCC is increasing in HIV-infected patients, especially those who are coinfected with HBV or HCV. As a result, people infected with HIV still face unique challenges in terms of their risk of developing HCC. To investigate the survival prognosis and clinical efficacy of surgical resection in patients with HCC complicated with HIV infection. The clinical data of 56 patients with HCC complicated with HIV admitted to the Third Affiliated Hospital of Nantong University from January 2013 to December 2023 were retrospectively analyzed. Among these, 27 patients underwent hepatectomy (operation group) and 29 patients received conservative treatment (nonoperation group). All patients signed informed consents in line with the provisions of medical ethics. The general data, clinicopathological features and prognoses for the patients in the two groups were analyzed and the risk factors related to the prognoses of the patients in the operation group were identified. The median disease-free survival (DFS) and overall survival (OS) of HIV-HCC patients in the surgical group were 13 months and 17 months, respectively, and the median OS of patients in the nonsurgical group was 12 months. The OS of the surgical group was significantly longer than that of the control group (17 months vs 12 months, respectively; P < 0.05). The risk factors associated with DFS and OS in the surgical group were initial HIV diagnosis, postoperative microvascular invasion (MVI), a CD4+ T-cell count < 200/μL, Barcelona stage C-D, and men who have sex with men (MSM; P < 0.05). Hepatectomy can effectively prolong the survival of patients with HIV-HCC but MVI identified during postoperative pathological examination, late tumor detection, late BCLC stage, CD4+ T < 200/μL and MSM are risk factors affecting the survival and prognosis of patients undergoing hepatectomy. In addition, there were significant differences between the surgical group and the nonsurgical group in terms of the initial diagnosis of HIV, Child-Pugh score, alpha-fetoprotein measurement value, and HART-efficient antiretroviral therapy after the diagnosis of HIV (P < 0.05). Therefore, these factors may also affect the survival and prognosis of patients.

Clinical characteristics and prognostic analysis of thoracic SMARCA4-deficient undifferentiated tumor

Objective: To summarize and analyze the clinical characteristics and prognosis of thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Methods: A retrospective analysis was conducted on the clinical data of 51 patients with SMARCA4-UT who were diagnosed in the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2023, and 52 patients with SMARCA4-intact non-small cell lung cancer (SMARCA4-iNSCLC) expression admitted during the same period were used as controls. The Kaplan-Meier survival analysis and log-rank test were used to analyze the survival difference between the two groups of patients, and the Cox regression model was used to explore the factors influencing the prognosis of the two groups of patients. Results: In the SMARCA4-UT group, there were 50 males and 1 female, with the age of (63.8±9.7) years. Compared to the SMARCA4-iNSCLC group, the SMARCA4-UT group exhibited a higher proportion of male patients and smokers, as well as a higher Ki-67 level (all P<0.05). SMARCA4-UT is mainly characterized by solid lesions with poor adhesion, and some of them exhibit rhabdomyoid morphology. Immunohistochemistry revealed negative results for BRG1, thyroid transcription factor-1, P40, NapsinA, and others were mostly negative, while some patients were positive for spalt-like transcription factor 4. There were a relatively large number of cases with Ki-67≥30% (47/51, 92%). Among the 10 patients in the SMARCA4-UT group who underwent next-generation sequencing genetic testing, 6 patients were found to have SMARCA4 mutations, often accompanied by TP53 (8/10, 80%), STK 11(3/10, 30%), KRAS(2/10, 20%), with fewer common driver gene mutations. The average tumor mutation burden was 16.12 mutations/Mb. Compared with SMARCA4-iNSCLC patients, the median overall survival of SMARCA4-UT patients was significantly shorter (12 months vs 45 months, P<0.001), and the median overall survival of patients with stage Ⅲ-Ⅳ SMARCA4-UT treated with immunotherapy was longer than that of patients without immunotherapy (23 months vs 7 months, P=0.027). The results of the multivariate Cox regression model analysis indicated that SMARCA4 deficiency is a risk factor for prognosis in patients with SMARCA4-UT and SMARCA4-iNSCLC [HR=7.954(95%CI： 2.764-22.890), P<0.001]. Conclusions: SMARCA4-UT is a rare undifferentiated tumour distinct from SMARCA4-iNSCLC, which is prevalent among elderly male smokers. It possesses high invasiveness and poor prognosis. The typical pathological characteristic is negative BRG1. Immunotherapy demonstrates a certain effect.

Real-World Analysis of Barriers to Timely Administration of Chimeric Antigen Receptor T Cell (CAR T) Therapy in Diffuse Large B-cell Lymphoma

The implementation of chimeric antigen receptor T (CAR T) therapy in the real-world setting is hindered by logistical and financial barriers, impacting timely access to this life-saving treatment. Clinical trials have reported the time from leukapheresis to CAR T cell infusion (vein-to-vein time) but not the time from CAR T referral to infusion (decision-to-vein time). Herein, we report the barriers to CAR T therapy in a real-world setting. We evaluated the factors influencing the decision-to-vein time and explored the association with clinical outcomes in patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) who received CAR T therapy. We conducted a retrospective study of adult patients with relapsed/refractory DLBCL who underwent consultation for CAR T cell therapy at Levine Cancer Institute and Wake Forest Comprehensive Cancer Center and collected information regarding demographic data, referral type, insurance type, CAR T product, and survival outcomes. The effects of variables on decision-to-vein time were analyzed by Fisher's exact test for categorial variables and Wilcoxon rank-sum test for continuous variables. Survival analyses were performed using Kaplan-Meier and Cox Proportional Hazard models. The study included 142 patients who were referred for CAR T of which 99 patients received CAR T. Median decision-to-vein time was 62 days compared to median vein-to-vein time of 32 days. Patients with private insurance took longer to obtain financial clearance compared to patients with government insurance (median 25 versus 9 days, P < .001). Of those with private insurance (n = 63), 35% needed a single-case agreement (SCA) which led to significant delay in receiving financial clearance (median 50.5 versus 19 days, P < .001) and increased decision-to-vein time (median 75 versus 55 days, P < .001) compared to those who did not need SCA. Decision-to-vein time was significantly different among various products, clinical trial being the shortest (median 47 days, n = 9) and non-conforming products being the longest (median 94.5 days, n = 6) (P< .001). Axi-cel had the shortest median decision-to-vein time at 61 days compared to 81 days with tisa-cel and 85 days with liso-cel. Although delays in receiving CAR T therapy did not impact survival, the median overall survival for patients who were referred for CAR T therapy but did not receive it, was significantly lower than those who received CAR T cell therapy (9.0 versus 21.0 months, P < .001). Decision-to-vein time is a major cause of delay in receiving CAR T therapy. SCAs lead to significant increase in decision-to-vein time leading to delays in CAR T therapy in a real-world setting. Patients who were referred for CAR T but are not able to receive it, have inferior survival compared to CAR T recipients. Our findings underscore the significance of addressing administrative hurdles, such as SCAs and insurance approvals, for timely access to CAR T therapy for patients with DLBCL.

Comprehensive genomic profiling in multiple cancer types: A comparative analysis of the National Biobank Consortium of Taiwan and clinical practice cohorts

BackgroundThis retrospective study analyzed tumor tissue profiling data to assess the potential of comprehensive genomic profiling (CGP) for patient care across diverse solid tumors. Material and methodsPatients with newly diagnosed or recurrent stage IIIB or IV lung adenocarcinoma with a null immunophenotype and esophageal, gastric, pancreatic, or bile duct cancer between January 2020 and July 2023 at two medical centers in Taiwan were included. One cohort was a part of the National Biobank Consortium of Taiwan project, whereas the other consisted of patients undergoing routine clinical practice. Tumor samples were subjected to CGP using FoundationOne®CDx, with therapeutic implications determined using OncoKB classification. ResultsFoundationOne®CDx testing of 574 patients was successful in 456 (79.4%) patients. Clinically actionable genomic alterations were detected in 21.1% (96/456) of the patients, including 17.5%, 2.9%, and 0.7% of patients with evidence levels 1, 2, and 3, respectively. Lung adenocarcinoma accounted for the largest proportion of samples with at least one actionable gene alteration (63.2%), followed by bile duct (26.9%), gastric (17.6%), esophageal (4.0%), and pancreatic (3.1%) cancers. Based on CGP results, 43 patients (9.4%) received matched targeted therapy. The median overall survival of patients who received matched therapy or not was 26.1 months (95% confidence interval (CI), 16.7–35.5 months) and 10.6 months (95% CI, 8.1–13.1 months; hazard ratio, 0.28, 95% CI, 0.14–0.55, p < 0.001), respectively. ConclusionsThis study provides comprehensive insights into the genomic profiles of diverse cancers in Taiwan, highlighting the crucial role of CGP in identifying actionable genomic alterations and guiding effective therapeutic strategies in real-world practice.

Effect of Low-Dose Aspirin Use After Thermal Ablation in Patients with Hepatocellular Carcinoma: A Retrospective Study.

To determine the effect of aspirin on hepatocellular carcinoma (HCC) recurrence and survival after thermal ablation. A retrospective analysis was performed to evaluate the efficacy and safety of aspirin in combination with thermal ablation. The clinical data were collected for the enrolled patients. Progression-free survival (PFS), overall survival (OS), and adverse events were analyzed. A total of 174 patients with HCC were enrolled. The median PFS was 11.1 (95% confidence interval [CI]: 8.1-14.0) months for patients who took aspirin and 8.6 (95% CI: 5.5-11.8) months for patients who did not take aspirin. The median OS of patients in the aspirin group was 76.7 (95% CI: 58.1-95.3) months and that in the non-aspirin group was 53.5 (95% CI: 42.7-64.3) months. In patients with non-viral HCC, OS was significantly better for the aspirin group (P = 0.03) after ablation. The PFS of patients who underwent ablation alone in the aspirin group was obviously superior to that of patients in the non-aspirin group (P = 0.002). Stratified Cox regression analysis demonstrated that aspirin use after ablation might be a protective factor in specific HCC patient subgroups. The incidence of major adverse events did not significantly differ between the two groups. Low-dose aspirin use was associated with better OS in patients with non-viral HCC after thermal ablation. In patients who received thermal ablation alone, the administration of low-dose aspirin could improve PFS. Aspirin use might be a protective factor in some patients after ablation.

Total laparoscopic radical resection of hilar cholangiocarcinoma: preliminary experience of a single center

BackgroundThe aim of this study was to describe our preliminary experience in the procedure of laparoscopic radical resection of hilar cholangiocarcinoma and to evaluate its feasibility, safety, and clinical efficacy.MethodsA retrospective analysis was conducted on 44 patients with hilar cholangiocarcinoma who underwent laparoscopic surgery at our hospital from August 2019 to September 2023. Clinical data were collected from these patients, including 13 cases of Bismuth type I, 17 cases of Bismuth type II, 5 cases of Bismuth type IIIa, and 9 cases of Bismuth type IIIb.ResultsLaparoscopic radical resection of hilar cholangiocarcinoma was successfully performed in 38 patients (86.3%). Among the remaining patients, 3 required vascular reconstruction to complete radical surgery and were converted to laparotomies, while 3 others underwent T-tube drainage only due to unresectable metastases. The median operation time was 285 min (range, 190–450), and the median estimated blood loss was 360 mL (range, 260–1200). The postoperative hospital stay duration was 14.3 ± 3.6 days. No perioperative mortality was observed. Postoperative pathological examination revealed negative microscopic margins (R0) in 39 cases and positive microscopic margins (R1) in 2 cases. Postoperative complications occurred in 8 patients (18.1%), with 4 cases (9.0%) of Grade I, 3 cases (6.8%) of Grade II, 1 case (2.2%) of Grade IIIa, and no Grade IIIb or IV complications. The median overall survival for patients who underwent radical R0 resection was 30.4 months (range, 5.3–43.6). The Disease-free survival rates were 73.6% at 1 year, 61.2% at 2 years, and 40.1% at 3 years.ConclusionTotal laparoscopic radical resection of hilar cholangiocarcinoma can be performed safely, feasibly, and effectively by experienced surgeons after an accurate preoperative evaluation.

Stereotactic body radiation therapy for the primary tumor and oligometastases versus the primary tumor alone in patients with metastatic pancreatic cancer

BackgroundLocal therapies may benefit patients with oligometastatic cancer. However, there were limited data about pancreatic cancer. Here, we compared the efficacy and safety of stereotactic body radiation therapy (SBRT) to the primary tumor and all oligometastases with SBRT to the primary tumor alone in patients with metastatic pancreatic cancer.MethodsA retrospective review of patients with synchronous oligometastatic pancreatic cancer (up to 5 lesions) receiving SBRT to all lesions (including all oligometastases and the primary tumor) were performed. Another comparable group of patients with similar baseline characteristics, including metastatic burden, SBRT doses, and chemotherapy regimens, receiving SBRT to the primary tumor alone were identified. The primary endpoint was overall survival (OS). The secondary endpoints were progression frees survival (PFS), polyprogression free survival (PPFS) and adverse events.ResultsThere were 59 and 158 patients receiving SBRT to all lesions and to the primary tumor alone. The median OS of patients with SBRT to all lesions and the primary tumor alone was 10.9 months (95% CI 10.2–11.6 months) and 9.3 months (95% CI 8.8–9.8 months) (P < 0.001). The median PFS of two groups was 6.5 months (95% CI 5.6–7.4 months) and 4.1 months (95% CI 3.8–4.4 months) (P < 0.001). The median PPFS of two groups was 9.8 months (95% CI 8.9–10.7 months) and 7.8 months (95% CI 7.2–8.4 months) (P < 0.001). Additionally, 14 (23.7%) and 32 (20.2%) patients in two groups had grade 3 or 4 treatment-related toxicity.ConclusionsSBRT to all oligometastases and the primary tumor in patients with pancreatic cancer may improve survival, which needs prospective verification.

Real-world insights from comprehensive genomic profiling across multiple cancer types.

106 Background: This retrospective study was conducted to analyze tumor tissue profiling data to assess the potential of applying comprehensive genomic profiling (CGP) in patient care across diverse solid tumors. Methods: Patients with newly diagnosed or recurrent stage IIIB or IV lung adenocarcinoma with the null immunophenotype, esophageal, gastric, pancreatic, or bile duct cancer between January 2020 and July 2023 at two medical centers in Taiwan were included in the National Biobank Consortium of Taiwan project. The tumor samples were subjected to CGP using FoundationOneCDx, with therapeutic implications determined using OncoKB classification. Results: FoundationOneCDx testing of 574 patients was successful in 456 (79.4%) patients. Clinically actionable genomic alterations were detected in 21.1% (96/456) of the patients, including 17.5%, 2.9%, and 0.7% of patients at evidence levels 1, 2, and 3, respectively. Lung adenocarcinoma accounted for the largest proportion of samples with at least one actionable gene alteration (63.2%), followed by bile duct (26.9%), gastric (17.6%), esophageal (4.0%), and pancreatic (3.1%) cancer. Based on the CGP results, 43 patients (9.4%) received matched targeted therapy. The median overall survival of patients who received matched therapy or not was 26.1 months (95% confidence interval (CI), 16.7–35.5 months) and 10.6 months (95% CI, 8.1–13.1 months; hazard ratio, 0.28, 95% CI, 0.14–0.55, p &lt; 0.001), respectively. Conclusions: This study provides comprehensive insights into genomic profiling across diverse cancers in Taiwan, highlighting the crucial role of CGP in identifying actionable genomic alterations and guiding effective therapeutic strategies in real-world practice.

Digital subtraction angiography-guided pancreatic arterial infusion of GEMOX chemotherapy in advanced pancreatic adenocarcinoma: a phase II, open-label, randomized controlled trial comparing with intravenous chemotherapy

BackgroundAdvanced pancreatic adenocarcinoma lacks effective treatment options, and systemic gemcitabine-based chemotherapy offers only marginal survival benefits at the cost of significant toxicities and adverse events. New therapeutic options with better drug availability are warranted. This study aims to evaluate the safety and efficacy of digital subtraction angiography (DSA)-guided pancreatic arterial infusion (PAI) versus intravenous chemotherapy (IVC) using the gemcitabine and oxaliplatin (GEMOX) regimen in unresectable locally advanced or metastatic pancreatic cancer (PC) patients.Materials and methodsThis study prospectively enrolled 51 eligible treatment-naive patients with unresectable PC to receive GEMOX treatment via PAI or IVC (1:1 ratio randomization) from December 2015 to December 2019. Cycles were repeated monthly, and each process consisted of two treatments administered bi-weekly. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), 1-year survival, 6-month survival, tumor-site subgroup survival, and incidences of adverse events were compared.ResultsThe median OS of the PAI and IVC groups were 9.93 months and 10.07 months, respectively (p = 0.3049). The median PFS of the PAI and IVC groups were 5.07 months and 4.23 months (p = 0.1088). No significant differences were found in the ORR (11.54% vs. 4%, p = 0.6312), DCR (53.85% vs. 44%, p = 0.482), and 1-year OS rate (44% vs. 20.92%, p = 0.27) in PAI and IVC groups. The 6-month OS rate was significantly higher in the PAI group (100%) than in the IVC group (83.67%) (p = 0.0173). The median OS of patients in PAI group with pancreatic head and neck tumors were significantly higher than those of body and tail tumors (12.867 months vs. 9 months, p = 0.0214). The incidences of hematologic disorders, liver function disorders, and digestive disorders in the IVC group were higher than in the PAI group (p < 0.05).ConclusionGEMOX PAI therapy presented a higher 6-month OS rate and fewer adverse events than IVC in advanced pancreatic adenocarcinoma patients. Those with pancreatic head and neck tumors may yield a superior treatment outcome from PAI treatment.Trial registration numberNCT02635971.Date of registration21/12/2015.

Analysis of high‑risk factors for brain metastasis and prognosis after prophylactic cranial irradiation in limited‑stage small cell lung cancer.

Small cell lung cancer (SCLC) is an aggressive malignancy with a high propensity for brain metastases (BM). Limited-stage SCLC (LS-SCLC) can be effectively treated with chemoradiotherapy and prophylactic cranial irradiation (PCI) to enhance patient outcomes. The aim of the present study was to assess the risk factors and prognostic significance of brain metastases (BM) in patients with limited-stage small cell lung cancer (LS-SCLC) who attained complete remission (CR) or partial remission (PR) following combined chemoradiotherapy and subsequent prophylactic cranial irradiation (PCI). Data for 290 patients diagnosed with LS-SCLC and treated at Chengde Central Hospital and Hebei Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine (Chengde, China), who achieved CR or PR and underwent PCI between 2015 and 2023, were retrospectively analyzed. BM rates and overall survival (OS) were estimated using the Kaplan-Meier method, whilst differences were assessed using the log-rank test. Risk factors affecting BM and OS were assessed using univariate and multivariate Cox regression analyses. The overall incidence of BM after PCI was 16.6% (48/290), with annual rates of 1.4, 6.6 and 12.8% at 1, 2 and 3 years, respectively. Multivariate Cox regression analysis identified an initial tumor size of >5 cm [hazard ratio (HR)=15.031; 95% confidence interval (CI): 5.610-40.270; P<0.001] as a significant independent risk factor for BM following PCI. The median OS was 28.8 months and the 5-year OS rate was 27.9%. The median OS for patients with and without BM at 27.55 and 32.5 months, respectively, and the corresponding 5-year OS rates were 8.3 and 31.8%, respectively (P=0.001). Median OS rates for stages I, II and III were 61.15, 48.5 and 28.4 months, respectively, with 5-year OS rates of 62.5, 47.1 and 21.6%, respectively (P<0.001). Further multivariate Cox regression analysis indicated that BM (HR=1.934; 95% CI: 1.358-2.764; P<0.001) and clinical stage (HR=1.741; 95% CI: 1.102-2.750; P=0.018; P=0.022) were significant independent risk factors associated with patient OS. In conclusion, a tumor size of >5 cm is a significant risk factor for BM following PCI in patients with LS-SCLS achieving CR or PR through radiotherapy and chemotherapy. Furthermore, BM and clinical staging independently influence OS.

Assessing survival in non-small cell lung cancer brain metastases after stereotactic radiosurgery: before and after the start of the targetable mutation era.

Targeted treatment options for non-small cell lung cancer (NSCLC) brain metastases (BMs) may be combined with stereotactic radiosurgery (SRS) to optimize survival. We assessed patient outcomes after SRS for NSCLC BMs, identifying survival trajectories associated with targetable mutations. In this retrospective time-dependent analysis, we analyzed median overall survival of patients who received ≥ 1 SRS courses for BM from NSCLC from 2001 to 2021. We compared survival of patients with and without targetable mutations based on clinical variables and treatment. Among the 213 patients included, 87 (40.8%) had targetable mutations-primarily EGFR (22.5%)-and 126 (59.2%) did not. Patients with targetable mutations were more often female (63.2%, p <.001) and nonsmokers (58.6%, p <.001); had higher initial lung-molGPA (2.0 vs. 1.5, p <.001) and lower cumulative tumor volume (3.7 vs. 10.6 cm3, p <.001); and received more concurrent (55.2% vs. 36.5%, p =.007) and total (median 3 vs. 2, p <.001) systemic therapies. These patients had lower mortality rates (74.7% vs. 91.3%, p <.001) and risk (HR 0.298 [95%CI 0.190-0.469], p <.001) and longer median overall survival (20.2 vs. 7.4 months, p <.001), including survival ≥ 3 years (p =.001). Survival was best predicted by SRS with tumor resection in patients with non-targetable mutations (HR 0.491 [95%CI 0.318-757], p =.001) and by systemic therapy with SRS for those with targetable mutations (HR 0.124 [95%CI 0.013-1.153], p =.067). The presence of targetable mutations enhances survival in patients receiving SRS for NSCLC BM, particularly when used with systemic therapies. Survival for patients without targetable mutations was longest with SRS and surgical resection. These results inform best practices for managing patients with NSCLC BM based on driver mutation status.