bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infusion-related reactions from immune checkpoint inhibitors: A proportional and network meta-analysis.
Authors: Fujiwara Yu , Tsuchiya Kazuya , Koseki Mako , Estaris Jonathan , Elias Evelyn , Chesta Fnu , Takaoka Kensuke , Nishimura Yoshito , Gopalakrishnan Dharmesh , Puzanov Igor 
Published: August 2024

38 Background: Immune checkpoint inhibitors (ICIs) have become the standard of care for the treatment of patients with solid tumors. Infusion-related reactions (IRRs) to ICIs have been reported in up to 20%, but the incidence varies among ICIs. Therefore, we aimed to report and compare the incidence of IRRs to each ICI therapy. Methods: We searched PubMed/MEDLINE, Embase, and Web of Science to identify phase 3 randomized controlled trials (RCTs) evaluating ICIs (CTLA-4, PD-1, PD-L1, and LAG-3 inhibitors) in solid tumors. We performed a random-effects model network meta-analysis to compare the odds ratio (OR) of IRRs by using RCTs comparing dual ICIs, ICI monotherapy, and placebo/observation. For a proportional meta-analysis, treatment arms evaluating ICI monotherapy, or dual ICIs, were selected to pool the incidence of IRRs. Results: A total of 25,250 patients from 47 phase 3 RCTs were included in the analysis. A network meta-analysis of treatment-related IRRs included 10 RCTs and showed that avelumab (OR 70.2, 95% confidence interval [CI]: 4.32-1140) and atezolizumab (40.72, 2.47-671.4) had a significantly higher risk of treatment-related IRRs compared with placebo/observation. Network ranking revealed that avelumab, atezolizumab, and relatlimab plus nivolumab were the top three therapies with risk of treatment-related IRRs. Proportional meta-analyses revealed that the pooled incidence of treatment-related IRRs was 5.39% for PD-1 plus CTLA-4 inhibitors, 8.25% for PD-L1 (avelumab: 13.1%, non-avelumab: 1.93%), 1.97% for CTLA-4, and 1.95% for PD-1 inhibitors. Results of immune-related IRRs were relatively consistent with those of treatment-related IRRs (Table). Conclusions: Avelumab has the highest risk of IRRs followed by atezolizumab and dual ICIs. This comparative study provides insight into the incidence of IRRs with ICI regimens. These results are useful in assessing which systemic therapies are responsible for IRRs, particularly when ICIs are combined with other agents. [Table: see text]
Surufatinib plus toripalimab in advanced soft tissue sarcoma (STS): Results from a multicenter, single-arm, basket study.
Authors: Cheng Ying , Zhang Xing , Lu Ming , Shi Si , Ye Feng , Chen Zhendong , Ji Dongmei , Song Lijie , Yin Fei , Shi Haiyan , Zhou Jinghong , Tan Panfeng , Fan Songhua , Xu Qian , Shi Michael , Su Weiguo 
Published: August 2024

42 Background: Soft tissue sarcomas (STS) are highly malignant despite their low incidence and prone to recurrence, with limited therapeutic options after failure of first-line treatment. Several antiangiogenic monotherapies have shown some efficacy but limited benefit. The open-label, multi-cohort, single-arm, basket study was performed to evaluate the efficacy and safety of the combination of surufatinib (a small-molecule inhibitor of VEGFR 1-3, FGFR1 and CSF-1R) with toripalimab (an anti-programmed death 1 [PD-1] antibody) for Chinese patients (pts) with advanced solid tumors. Here, we reported the results from the STS cohort. Methods: Pts with STS who had progressed on ≤ 2 lines of systemic chemotherapy, or were intolerant to standard treatment, or for whom there was currently no effective therapy were eligible. They received 21-day cycles of surufatinib 250 mg orally, once daily, plus toripalimab 240 mg intravenously, once every 3 weeks, until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST 1.1. Results: As of data cutoff (Feb 28, 2023), a total of 20 pts (incl. 4 treatment-naïve pts) were enrolled and received the combination treatment (mean duration: 5.81 months [m]). Median (range) age was 50 (23-74) years, 10 pts were male, 17 pts were TNM stage IV. The pathological types include leiomyosarcoma (n=4, incl. 1 naïve patient), synovial sarcoma (n=4), alveolar soft part sarcoma (n=3, incl. 2 naïve pts), undifferentiated pleomorphic sarcoma (n=3), liposarcoma (n=2, incl. 1 naïve patient) and fibrosarcoma (n=1), malignant fibrous histiocytoma (n=1) and others (n=2). Seven (35%) pts had PD-L1 combined positive score of ≥1. The median follow-up duration was 27.14 m. Confirmed ORR and disease control rate (DCR) for 19 efficacy-evaluable pts was 10.5% and 68.4%, respectively; median duration of response was 7.05m. The median progression-free survival (mPFS) and median overall survival (mOS) was 2.69 m and 16.23 m for all dosed pts. For 16 previously treated pts, ORR and DCR was 6.3% and 62.5% respectively; median duration of response (DoR) was 7.13 m; mPFS was 2.65 m; mOS was 14.32 m. 18 (90%) pts experienced at least one treatment-related adverse event (TRAE), and 7 (35%) of them reported grade ≥3 TRAEs. The incidence of immune-related adverse events (irAEs) was 70%, only 2 pts had grade ≥3 irAEs, which were immune-related pancreatitis and immune-related diabetes. 2 pts were permanently discontinued due to TRAEs, which were grade 2 renal impairment and grade 3 hyperglycemia. No new safety signals were observed. Conclusions: Surufatinib plus toripalimab had a promising antitumor activity and a manageable safety profile in pts with advanced STS. Clinical trial information: NCT04169672 .
A phase I/II study of nanoliposomal irinotecan and carboplatin in patients with advanced or metastatic, poorly differentiated gastroenteropancreatic neuroendocrine carcinoma characterized by tissue and liquid next-generation sequencing.
Authors: Chiang Nai-Jung , Li Chien-Feng , Bai Li-Yuan , Huang Chien-Jui , Yen Chih Chieh , Hsiao Chin-Fu , Wu Li-Ching , Chen Ming Huang 
Published: August 2024

52 Background: For locally advanced or metastatic gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs), standard chemotherapy typically incorporates etoposide or irinotecan plus platinum agents. Herein, we initiate a phase I/II trial to apply Nal-IRI in combination with carboplatin as the 1st line treatment in patients with GEP-NECs to define the dose-limiting toxicity (DLT) and recommended phase II dose (RP2D). Methods: In the phase I part, traditional 3+3 design was applied. Enrolled patients would receive escalating dose of 60 (level -1), 80 (starting dose, level 0) or 100 (level 1) mg/m2 salt-form nal-IRI plus carboplatin AUC=4 with maximum total dose of 600 mg on D1, every 21 days as a cycle. DLTs were evaluated during the first one cycle of treatment with tumor assessment every 6 weeks. Prophylaxis G-CSF was not allowed in the first cycle Paired testing of tissue (TBx) and liquid biopsy (LBx) was done by Illumina TSO500 platform before treatment. The second LBx would be repeated for confirmed partial responders when progression. Results: Totally 6 GEP-NEC patients with primary sites of colon in three, and each one in esophagus, ampulla of Vater and pancreas were enrolled to level 0. One patient had DLT of grade 4 neutropenia lasting for 3 days even under salvage G-CSF. Treatment-related adverse events showed grade 3/4 neutropenia (33.4%), grade 2 anemia (16.7%), grade 3 fatigue (16.7%), and grade 2 skin rash (16.7%). Four patients achieved confirmed partial response and 2 patients got stable disease, with the objective response rate of 66.7% (95% confidence interval: 22%-96%). After the data and safety monitoring board meeting, level 0 was decided as RP2D but not escalation to level 1 because of acceptable toxicity profiles and promising efficacies. Comprehensive genomic profiling showed that driver mutations were identified in three cases including two harboring BRAFV600E mutation and one with KRASG12D mutation. The other three cases lacking driver mutation showed frequent copy number alteration including 1 with MDM2 amplification (copy number 27) and a wild-type TP53. Homologous recombination deficiency (HRD), as determined by GIS score, was identified in a colon GEP-NEC who remained to be HRD-positive at progression but a higher TMB (from 4.7 to 10.2 Muts/Mb) and a higher BRAFV600E mutation allele frequency (from 24.1% to 43.6%) in tumor tissue, compared to the baseline profiling. Conclusions: Based on current data, the RP2D is 80 mg/m2 of nal-IRI (salt-form) and carboplatin of AUC=4, every 3 weeks. The extension phase II study in GEP-NEC is ongoing. Clinical trial information: NCT05385861 .
Navigating the future of pancreatic cancer treatment: Systematic review insights from immunotherapy clinical trials.
Authors: Sarfraz Zouina , Anwar Junaid 
Published: August 2024

68 Background: Pancreatic cancer remains a formidable challenge, being the seventh leading cause of cancer-related deaths globally. Despite advances in medical science, survival rates have not significantly improved, primarily due to late diagnosis and the limited efficacy of conventional treatments. This study investigates the potential of immunotherapy, offering a new horizon for treatment strategies. Methods: A systematic review was conducted, encompassing Phase I-III clinical trials that utilized immunotherapy in treating pancreatic cancer. Databases such as PubMed/Medline, CINAHL, Scopus, and ClinicalTrials.Gov were searched following PRISMA guidelines. A total of 29 completed trials and 106 ongoing studies were analyzed, focusing on survival rates, response to treatment, and adverse events. Results: Analysis of 29 completed clinical trials revealed that immunotherapy could extend the median OS in selected cohorts, with a notable trial showing an increase in OS from 6 to 13.6 months in patients receiving PD-1 blockers. Phase I trials demonstrated a cumulative OS of 13.6 months and a PFS of 5.1 months across various interventions. Ongoing studies, numbering 106, are exploring a wide range of immunotherapeutic agents, aiming to improve these outcomes further. Adverse events were consistent with expectations for immunotherapy, indicating a manageable safety profile. The most promising interventions appear to be combination therapies that include checkpoint inhibitors, showing an increase in the 5-year survival rate of up to 30% for patients undergoing adjunctive treatment post-surgery. Conclusions: Immunotherapy presents a potential paradigm shift in the treatment of pancreatic cancer. However, more robust clinical trials are necessary to fully understand its efficacy and safety. Future research should focus on identifying biomarkers for patient selection and exploring combination therapies to enhance treatment responses. The disparity in access to these therapies, especially in low- and middle-income countries, underscores the need for global efforts to make advanced treatments more accessible.
Circulating tumor DNA analysis in patients with esophageal cancer treated with neoadjuvant chemoradiotherapy followed by surgery.
Authors: Xie Mian 
Published: August 2024

69 Background: The aim of this prospectively study is to investigate circulating tumor DNA (ctDNA) as a prognostic marker for survival in locally advanced esophageal squamous cell cancer (ESCC) patients treated with neoadjuvant chemoradiotherapy (nCRT) and surgery. Methods: Serial plasma samples were collected from 68 ESCC patients treated with neoadjuvant chemoradiotherapy before surgery. ctDNA was detected before treatment, after neoadjuvant chemoradiotherapy and after surgery by personalized, next-generation sequencing assay. Cox regression analyses were used to evaluate the prognostic significance of ctDNA for recurrence-free survival (RFS) and overall survival (OS). Results: ctDNA was detectable in 89.7%, 17.2%, and 6.9% of pretreatment, post-neoadjuvant chemoradiotherapy and post-surgery plasma samples, respectively. The conversion of ctDNA status from positive at baseline to negative at 4-6 weeks after neoadjuvant chemoradiotherapy was significantly associated with pathological complete response (pCR) ( P = 0.02). Significant worse RFS was related to detectable ctDNA after neoadjuvant chemoradiotherapy ( P = 0.008) or after surgery ( P = 0.001). Detectable ctDNA at baseline ( P = 0.01) and after surgery ( P = 0.008) were associated with worse OS. In multivariate analysis, detectable postoperative ctDNA was significantly associated with RFS ( P = 0.012) and OS ( P = 0.025) after adjusting for other clinicopathological risk factors. Conclusions: ctDNA status is a strong prognostic factor of recurrence in locally advanced ESCC patients. Consequently, ctDNA could potentially improve pre- and post-treatment risk assessment and facilitate individual therapy for ESCC patients.
Association of vitamin D deficiency with liver cirrhosis and hepatocellular carcinoma risk: A retrospective cohort study from the TriNetX US collaborative networks.
Authors: Tseng Yuan-Tsung , Wang Chun-Hsiang 
Published: August 2024

77 Background: Emerging evidence highlights the critical role of vitamin D in liver health, especially concerning the risk of liver cirrhosis and hepatocellular carcinoma (HCC). This investigation aims to explore the association between vitamin D deficiency and the prevalence of these liver diseases, contrasting outcomes between individuals with deficient and normal vitamin D levels. Methods: This cohort study utilized the US Collaborative Network within the TrinetX database, encompassing 63 medical institutions. It enrolled participants aged 20 years and older from 2011 to 2023. Vitamin D status was determined through serum 25-hydroxyvitamin D levels, categorizing deficiency as 20-30 ng/mL and normal levels as 30-80 ng/mL. Employing 1:1 propensity score matching, the study controlled for 32 characteristics, such as demographic information, health conditions, and medication use, to ensure equitable group comparisons. Additionally, a 1-year washout period was established. The primary aim was to assess the incidence of liver cirrhosis and HCC over a decade. Results: Analyzing data from over 1.86 million participants, the study ensured a balanced comparison across all variables. Participants had an average age of 50.6 years, with 66% identifying as white and 9% as black. Notably, vitamin D deficiency was significantly associated with an increased risk of liver cirrhosis (HR 1.16 [CI 1.11-1.21]) and HCC (HR 1.25 [CI 1.15-1.36]). Kaplan-Meier cumulative risk analysis further confirmed these elevated risks for both liver conditions in individuals with vitamin D deficiency compared to those with sufficient levels. Conclusions: This study confirms a significant association between vitamin D deficiency and a higher risk of liver cirrhosis and HCC, underscoring the importance of vitamin D in maintaining liver health. The findings support the potential of vitamin D level management as a preventive strategy against liver diseases. The implications of this research necessitate further exploration into the efficacy of vitamin D supplementation for liver disease prevention.
Comparative analysis of cirrhosis and hepatocellular carcinoma outcomes in Asian populations with non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated steatohepatitis liver disease (MASLD): A five-year retrospective study.
Authors: Tseng Yuan-Tsung , Wang Chun-Hsiang 
Published: August 2024

78 Background: Metabolic Dysfunction-Associated Steatohepatitis Liver Disease (MASLD) represents the most up-to-date definition of Non-Alcoholic Fatty Liver Disease (NAFLD) for Asian populations, acknowledging that manifestations may differ across racial/ethnic groups. Due to metabolic and anthropometric differences, adapted criteria for MASLD have been proposed for Asian adults. This analysis aims to compare clinical outcomes between Asian patients diagnosed with MASLD and those with NAFLD. Methods: In this retrospective analysis, 48,189 Asian adults suspected of having MASLD were identified from the TriNetX global research network between January 1, 2010 and December 31, 2023. An equal number of patients (48,189) diagnosed with NAFLD were matched on a 1:1 basis with MASLD patients through propensity score matching. MASLD criteria were adapted to be Asia-specific, requiring a Body Mass Index (BMI) of ≥23 along with the presence of four aspects of metabolic dysfunction. Over a 5-year follow-up period, primary outcomes of cirrhosis and hepatocellular carcinoma (HCC) incidences were determined using Kaplan-Meier methods. Cumulative incidence curves depicted the rates of these events over time. Hazard ratios (HR) for the outcomes were calculated using Cox regression models to estimate the risk associated with MASLD. Results: Over 5 years, the cumulative incidence of cirrhosis (3.0% vs 3.0%, p=0.800) and HCC (1.3% vs 1.4%, p=0.695) were numerically lower in MASLD compared to NAFLD patients, respectively. Adjusted HRs for MASLD were: cirrhosis 1.00 (0.87-1.14) and HCC 0.86 (0.68-1.10). Conclusions: This study compared the clinical outcomes of MASLD and NAFLD in Asian populations and found no significant differences in identifying the risk of cirrhosis and hepatocellular carcinoma between the two diagnostic criteria. However, introducing the new term and diagnostic criteria of MASLD helps reduce the stigmatization associated with NAFLD, emphasizing the central role of metabolic dysfunction in disease occurrence. Although this study did not find significant differences between MASLD and NAFLD in predicting cirrhosis and hepatocellular carcinoma, the concept of Asian-specific diagnostic criteria remains important, highlighting that disease manifestations and risk factors may vary across different races and populations, necessitating personalized prevention and treatment strategies for specific populations. Future research should further explore the similarities and differences between MASLD and NAFLD in different Asian subgroups to optimize diagnostic criteria, improve the accuracy of risk prediction, and develop targeted interventions.
Impact of EOB-MRI on the outcome of patients with pancreatic cancer in real-world settings.
Authors: Oba Atsushi , Taguchi Tomoyuki , Fujikawa Naoto , Okami Suguru , Tsuji Takashi , Michel Alexander , Kado Yuki , Goshima Satoshi 
Published: August 2024

88 Background: Contrast-enhanced computed tomography (CE-CT) is a commonly used imaging modality for the preoperative detection of local extension and distant metastasis in patients (pts) with pancreatic cancer (PaC). There have been cases where surgical treatment was deemed unsuitable due to unexpected distant metastases discovered during surgery, which had not been detected by CE-CT. While studies have reported gadoxetate disodium-enhanced MRI (EOB-MRI) improves the detection of liver metastases, it is not clear whether adding EOB-MRI to CE-CT provides clinical benefits, e.g. improved outcomes through the early access to appropriate treatments by avoiding unnecessary surgery (open-close surgery) in pts with PaC. This study aimed to assess the effectiveness of adding EOB-MRI before surgical or non-surgical treatment on overall survival (OS) in pts with PaC in real world settings. Methods: This was a retrospective cohort study using a nationwide hospital-claims database in Japan. Pts aged ≥18 years diagnosed with PaC with a record of surgery, radiotherapy, or chemotherapy, who had an imaging modality were identified between January 1, 2011 to October 31, 2021. Pts were grouped into EOB-MRI and no EOB-MRI groups, and further grouped into surgery, no surgery and open-close laparotomy. OS was compared between propensity-score matched EOB-MRI and no EOB-MRI groups using the Cox regression model. Results: 39,624 pts were included in the study, of them, 4,477 (11.3%) underwent EOB-MRI prior to the initial treatment. 2,061 (46.0%) pts in EOB-MRI group underwent surgery, 2,346 (52.4%) had no surgery and 70 (1.6%) had open-close laparotomy. In 35,147 (88.7%) pts in no EOB-MRI group, 13,182 (37.5%) underwent surgery, 21,506 (61.2%) had no surgery, and 459 (1.3%) had open-close laparotomy. The OS results in subgroups are shown in the Table. Conclusions: In real-world settings, EOB-MRI performed prior to the initial treatment was associated with significantly higher OS than those without EOB-MRI in pts who did not undergo surgery, but there was no difference in OS in pts who underwent surgery. These results suggest that the early detection of micro hepatic metastases through EOB-MRI and multidisciplinary treatment that enables EOB-MRI may contribute to improved outcomes in pts with PaC. Clinical trial information: NCT06106568 . [Table: see text]
The correlation between L1CAM expression and outcomes in patients with metastatic colorectal cancer treated with first-line chemotherapy.
Authors: Pretta Andrea , Cau Flaviana , Ziranu Pina , Spanu Dario , Donisi Clelia , Moledda Giusy , Cadoni Andrea , Cimbro Erika , Murgia Sara , Mariani Stefano , Lai Eleonora , Puzzoni Marco , Pusceddu Valeria , Faa Gavino , Scartozzi Mario 
Published: August 2024

95 Background: L1CAM is a cell adhesion molecule and stem cell marker belonging to the immunoglobulin superfamily of cell adhesion molecules (IgCAMs). L1CAM may be aberrantly expressed in several types of human tumors. The aim of the present study was to evaluate the correlation between L1CAM expression and outcomes in patients with metastatic colorectal cancer. Methods: We retrospectively collected data from 51 mCRC pts treated between 2017 and 2022 at the Medical Oncology Unit of the University Hospital of Cagliari. Tumor samples were retrospectively tested for L1CAM immunohistochemical (IHC) expression with the aim of evaluating the correlation with clinical outcome in terms of overall survival (OS) and progression-free survival (PFS). The primary endpoint was the mOS while secondary endpoint was mPFS. The aim of the present analysis was to evaluate the role of L1CAM expression in tumor cells in predicting the clinical outcome of CRC patients treated with standard chemotherapy. Statistical analysis was performed with the MedCalc Statistical Sofware Version 14.10.2. Results: Median age was 70 (±13), 58.8% were males and 41.2% were females. 29.4% of pts had carcinoma of the right colon, 39.2% left colon and 31.4% rectum. Negative or weak L1CAM score 0 was observed in 39.2% patients; 43.1% pts showed a score 1+; 11.8% showed score 2+, and 5.9% showed score 3+. Positivity for L1CAM correlated with a worse prognosis. The median OS for pts not expressing L1CAM was 74.0 months versus 32.0 for patients expressing the biomarker ( p = 0.0021). The mPFS for patients not expressing L1CAM was 21.0 months, vs 6.0 for patients expressing the biomarker ( p = 0.0066). The same negative correlation on outcomes was shown based on the degree of L1CAM expression. A different L1CAM score corresponded to a different OS and PFS. Pts with score 0 showed a mOS of 74 months vs 37 and 18 months for scores 1+ and 2+/3+, respectively ( p < 0.0001). Similar results were obtained with the mPFS: patients with score 0 showed a median of 21 months vs 8 and 2 months for scores 1+ and 2+/3+, respectively ( p = 0.0138). Conclusions: L1CAM expression in cancer cells correlates with a worse prognosis in mCRC patients. Immunohistochemical evaluation of this biomarker could allow the identification of a subgroup of patients capable of benefiting from a targeted therapy.
Ultrasound-Guided Microwave Ablation of Thyroid Schwannoma
Authors: Han Xue , Zhang Yuzhi , Li Yu , Li Ruiping , Liu Chao , Xu Shuhang 
Published: August 2024

Abstract
Thyroid schwannoma, a rare neoplasm of the thyroid gland, originates from Schwann cells that form the myelin sheath. A 47-year-old woman presented with a progressively enlarging thyroid nodule, which was monitored by repeated ultrasonography over the previous 2 years. Following a diagnosis of thyroid schwannoma by core needle biopsy and immunohistochemical staining, the patient underwent ultrasound-guided microwave ablation (MWA). Subsequent thyroid ultrasounds indicated a gradual decrease in the tumor's volume, achieving a 12-month volume reduction ratio of 79.20%. No complications were observed. Ultrasound-guided MWA may serve as an effective alternative to conventional surgery for managing thyroid schwannomas.