bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of T cell infiltration in hepatocellular carcinoma between whole exome and transcriptome sequencing data.
Authors: Lv Xing , Dong Wei , Zhang Zunyi , Li Jian , Wang Wenqiang , Dong Linfeng , Yang Zuoquan , Zhou Yanqing , Zhao Shuhua , Chen Shifu , Zhang Erlei 
Published: June 2023

e16226 Background: Immunotherapy is one of the most promising therapeutics for hepatocellular carcinoma (HCC), and the immune infiltration status in tumors could be used as a biomarker for immunotherapy. However, evaluation of immune infiltration is usually based on RNA-Seq (transcriptome sequencing), which is limited in clinical practice due to the difficulty of handling RNA. On the other hand, WES (whole exome sequencing) is frequently performed to detect tumor mutations in cancer clinic. Therefore, we try to compare T cell infiltration in hepatocellular carcinoma obtained from WES data and RNA-Seq data, evaluate the potential of T cell infiltration from WES data as a biomarker for immunotherapy. Besides, we also evaluated the association of T cell fraction obtained from WES data and other clinical information. Methods: Seventy pairs of HCC tumor and matched normal tissue samples underwent both WES and RNA-Seq. T cell ExTRECT score and mcpCounter score were used to represent the immune infiltration status, and they were generated from WES data and RNA-Seq data respectively. Tumor mutational burden (TMB) score and some characteristics (tumor size, blood pressure, etc.) were also calculated for correlation analysis. Results: T cell ExTRECT score was positively correlated with mcpCounter score (Spearman correlation coefficient: 0.54). While TMB score showed no correlation with T cell ExTRECT score (Spearman correlation coefficient: -0.06) and mcpCounter score (Spearman correlation coefficient: -0.09). Besides, T cell ExTRECT score was negatively associated with main tumor size (Spearman correlation coefficient: -0.38) and High Blood Pressure (Spearman correlation coefficient: -0.37). Conclusions: These results suggest that T cell ExTRECT score obtained from WES and mcpCounter score generated by RNA-seq data is highly correlated, and neither of them is associated with TMB score. T cell ExTRECT score could be used to evaluate immune infiltration in hepatocellular carcinoma, and may serve as a biomarker for immunotherapy regardless of TMB score. Further investigation is still needed to evaluate the clinical outcome of immunotherapy for hepatocellular carcinoma with T cell ExTRECT score.
An observational study of donafenib as adjuvant therapy to prevent hepatocellular carcinoma recurrence after curative surgery.
Authors: Shang Changzhen , Zhong Jinyi , Luo Xuan , Zhang Jianlong , Li Huilong , Hua Yonglin , Tan Wenliang , Lei Zhang , Chen Yajin 
Published: June 2023

e16227 Background: The five-year recurrence rate of hepatocellular carcinoma (HCC) after hepatic resection is as high as 70% and remains a major clinical challenge. Many investigators have suggested adjuvant therapy to prevent HCC recurrence, and several promising outcomes have been reported. Donafenib has been approved as a standard treatment for patients with unresectable HCC in China. Here, we describe our preliminary results regarding the efficacy and safety of donafenib as an adjuvant therapy for patients with HCC after hepatectomy. Methods: This was an observational study of patients with HCC following hepatectomy treated with donafenib in routine practice at Sun Yat-sen Memorial Hospital, Sun Yat-sen University. The enrolled patients were 75 years or younger, had been diagnosed with HCC, showed no evidence of recurrence at radiological follow-up within one month after hepatectomy, and had at least one high recurrence risk factor, such as tumor diameter ≥5 cm, tumor number ≥2, microvascular invasion, or serum a-fetoprotein level before surgery ≥400 ng/mL. All of the patients had adequate hematologic, hepatic, and renal functions. The primary endpoint was recurrence-free survival (RFS), and the secondary endpoints included 6- and 12-month RFS rates, overall survival, and adverse events. Results: Seventeen patients were enrolled in this study. The median age was 56 years (range, 40–72), 88.2% were males, 82.4% with HBV, 17.6% had preoperative serum a-fetoprotein levels ≥400 ng/mL, 35.3% had tumor diameters ≥5 cm, 29.4% had tumor numbers ≥2, and 29.4% had microvascular invasion. The median follow-up time for the entire patient cohort was 16 months (95% confidence interval [CI], 11.9–20.1), and 5 of 17 patients relapsed, with a recurrence rate of 29.4%. The median RFS was not reached; the 6- and 12-month RFS rates were 88.2% and 70.1%, respectively. Treatment-related adverse events (TRAEs) occurred in 82.4% of the patients, most of which were grades 1–2. Grade 3 TRAEs, including hand-foot skin reaction and rash, were observed in three (16.4%) patients. No grade 4 or 5 TRAEs occurred. Conclusions: The findings of the present study suggest that donafenib as adjuvant therapy may be a potentially effective way to prevent HCC recurrence after curative surgery. Our findings should be validated in a larger, prospectively evaluated sample. Clinical trial information: ChiCTR2200064030 .
Introducing yttrium-90 radioembolization to atezolizumab and bevacizumab regimen for intermediate and advanced stage hepatocellular carcinoma: A preliminary report of safety and effectiveness.
Authors: Yu Qian , Wang Yating , Ungchusri Ethan , Patel Mikin , Pillai Anjana , Van Ha Thuong , Liao Chih-Yi , Ahmed Osman 
Published: June 2023

e16231 Background: The IMbrave150 Phase III trial demonstrated superiority of atezolizumab and bevacizumab (Atezo/Bev) over sorafenib in unresectable hepatocellular carcinoma (HCC). Combined radiotherapy and immune checkpoint inhibitors have been shown to induce synergistic effects in treatment of HCC and other solid tumors. Barcelona Clinic Liver Cancer 2022 updated guidelines recommend consideration of transarterial radioembolization (TARE) for early stage and very early stage HCC. The present study sims to evaluate the safety and effectiveness of combining TARE and the Atezo/Bev regimen for intermediate and advanced stage HCC. Methods: Retrospective review at a single institution was performed between May 2021 and December 2022. Patients who received TARE using yttrium-90 (Y90) with concomitant or sequential Atezo/Bev systemic treatment were included. The following outcomes were retrieved: overall survival (OS), radiologic tumor response, progression-free survival, technical adverse events related to TARE, and toxicity based on the National Cancer Institute–Common Terminology Criteria for Adverse Events version 5.0. Results: Ten consecutive patients (9 male, 1 female) with unresectable HCC received TARE and Atezo/Bev were included. A total 21 of doses of Y90 were administered with a median target dose of 156 Gy. Tumor control was achieved in all target lesions (100%) based on modified Response Evaluation Criteria in Solid Tumors criteria. Overall disease progression occurred in 4 patients after TARE with a 6- month PFS of 80% (95%CI: 40.9-95.6%) and 12-month PFS of 53.3% (17.3%-79.8%). Two patients died during follow-up, with 6-month and 12-month OS rates of 88.9% (95%CI: 43.3-98.4%) and 76.2% (95%CI: 33.2-93.5%), respectively. One patient developed grade 3 transaminitis and hypoglobulinemia. Atezo/Bev was switched to Lenvatinib in one patient due to myositis. Bevacizumab was held in one patient due to suspected transient ischemic attack. Conclusions: This small patient cohort demonstrated preliminary safety and effectiveness of TARE in combination with Atezo/Bev in treating intermediate and advanced stage HCC. Further prospective and comparative studies with large sample sizes are warranted.
Neoadjuvant immunotherapy in hepatocellular carcinoma: A systematic review and meta-analysis.
Authors: Parekh Jay , Abraham Soniya , Andanamala Haripriya , Rehman Asad , Xie Yiyu , Adjepong Yaw , Stein Stacey 
Published: June 2023

e16232 Background: The addition of immunotherapy in neoadjuvant hepatocellular carcinoma (HCC) has been studied recently in early phase clinical trials due to high rate of recurrence after surgery. We aim to systematically review the evidence of efficacy and safety of neoadjuvant immunotherapy treatment. Methods: We carried out a systematic search on MEDLINE, Cochrane, and ASCO meetings library. Screening was done to include clinical trials with HCC patients who underwent any combination of neoadjuvant immune checkpoint inhibitors (ICIs). Quality assessment was performed using methodological index for non-randomized studies (MINORS) tool. The primary efficacy outcomes evaluated included complete pathological response (pCR), major pathological response (MPR), 1 year recurrence free survival (RFS) and overall response rate (ORR). Treatment related adverse events (TRAE) were assessed as a safety outcome. Predefined subgroup analysis was performed based on studies including of tyrosine kinase inhibitors (TKIs) in regimen. Data was analyzed using R version 4.2.1. Results: 5 phase I/II clinical trials were included consisting of 96 patients. Trials administered neoadjuvant immunotherapy agents nivolumab (with TKI cabozantinib) (N = 1), camrelizumab (with TKI apatinib) (N = 1), cemiplimab (N = 1) and nivolumab plus ipilimumab (N = 2). 78(81.2%) of patients were males. 56(59.3%) of patients had viral etiology. 14(14.5%) patients had surgeries delayed or cancelled due to any cause per trial protocols. Meta-analysis of 96 patients from 5 trials showed a pooled pCR rate of 14.49% (95% CI: 6.82 to 23.93%) with low heterogeneity (I2 = 0%, p value 0.55). Pooling the MPR resulted in an estimate of 35.30% (95% CI: 18.80% to 53.57%) with significant heterogeneity (I2 = 58.8%, p value 0.04). Three trials with total 45 patients reported a 12-month RFS rate of 51.08% (95% CI: 40.59 to 70.67%) with significant heterogeneity (I2 = 84.2%, p value 0.002). The overall response rate was 13.7% (95% CI: 6.9 to 22.1%) (I2 =0%, p =0.8). Overall rate of TRAE of any grade was 73.8% (95% CI: 63.1 to 82.5%) (I2 = 83.4%, p <0.001) among all trials and grade 3 adverse events was 21.21% (95% CI: 11.4 to 32.7%) (I2 = 33.8%, p = 0.159). 17(17.8%) patients had elevation in liver enzymes. On subgroup analyses, no difference in pathological outcomes, ORR and grade 3 adverse events was observed with addition of TKIs. Exploratory analysis showed no difference in pCR rates with single ICI vs combination with ipilimumab. Conclusions: The addition of ICIs in neoadjuvant settings appears to be a safe and feasible option. The addition of TKIs to neoadjuvant ICIs does not appear to affect pathological and safety outcomes. Further studies are needed to identify ICI based regimens to improve pCR rates and validate pathological outcomes in HCC after correlating with recurrence and survival.
Incidence of hepatocellular cancer in India: Analysis of population based cancer registry data.
Authors: Gopalakrishna Harish , Huang Bin , Mathew Aju 
Published: June 2023

e16233 Background: Hepatocellular cancer (HCC) is the most common primary liver cancer and the third most common cause of cancer death globally. HCC incidence rate is declining in certain highly prevalent regions, however, continues to rise in many countries where the prevalence is currently low. To understand the trend of HCC incidence in India, we analyzed HCC incidence from various regions in India from 2004 to 2014. Methods: We obtained data on HCC incidence from the Population Based Cancer Registries (PBCR) of the National Cancer Registry Program. This registry includes data from different regions spread across India. We calculated age-standardized incidence rates (to WHO World standard population 2000) for periods of diagnosis (2004-05, 2006-08, 2009-11, and 2012-14). Results: From 2004 to 2014, HCC incidence rates increased relatively by 11%. When compared to data from 2004-2005, HCC incidence rate increased absolutely from 3 per 100,000 persons to 3.3 per 100,000 persons in 2012-2014. From 2004 to 2014, the relative increase in incidence rate was 13.3% in males and 7.4% in females. Conclusions: Rising HCC incidence rate is a cause for concern in India. Globally Nonalcoholic fatty liver disease (NAFLD) is swiftly becoming the most important cause of HCC. The rise in HCC incidence in India could be likely due to the increasing prevalence of NAFLD. Effective strategies are needed to improve surveillance and early diagnosis in patients with high risk of developing hepatocellular cancer. NAFLD preventive strategies must be an urgent public health measure in India.[Table: see text]
Real world sequence of peptide receptor radionucleotide therapy (PRRT) and chemotherapy in patients with metastatic pancreatic neuroendocrine tumors (pNETs).
Authors: Phillips William James , Tsvetkova Elena , Leung Macyn , Nair Gautham , Welch Stephen , Laidley David , Asmis Tim , Vickers Michael M. , Black Morgan , Sachdeva Robin , Marginean Horia , Goodwin Rachel Anne 
Published: June 2023

e16237 Background: Peptide Receptor Radionuclide Therapy (PRRT) is an effective therapy for advanced pNETs but carries long-term risks of myeloid neoplasia. Early data from United States centres may suggest a higher risk of myelodysplasia and leukemia in patients treated with temozolomide prior to PRRT. The objective of this study is to characterize the sequence of PRRT and chemotherapy at two Canadian pNET treatment centres, distinguished by the availability of PRRT. Methods: This is a multicentre retrospective cohort study involving The Ottawa Hospital Cancer Centre (TOHCC; PRRT non-treatment centre (PRRT-NTC)) and London Regional Cancer Centre (LRCC; PRRT treatment centre (PRRT-TC). Patients with histologically confirmed pNETs between January 2010 – June 2021 over the age 18 (n=226), with metastatic disease (n=177) were included. Demographic, clinical and cancer treatments were collected. Descriptive statistics were used to evaluate the sequence of systemic therapy. Results: 177 patients with metastatic pNET were identified. Systemic therapies included octreotide (n=59, 40%), lanreotide (n=47, 32%), targeted agents (n=40, 27%), chemotherapy (n=48, 33%) and PRRT (n=47, 32%). Of patients receiving chemotherapy, 22 (46%) received temozolomide-containing regimens. The most frequent first line therapies were somatostatin analogues (SSAs, n=76, 43%), chemotherapy (n=23, 13%) and observation (n=18, 10%), second-line were PRRT (n=24, 14%), targeted therapy (n=26, 15%) and SSA (n=13, 7%), and third-line were PRRT (n=15, 9%), chemotherapy (n=11, 6%) and targeted therapy (n=8, 5%). There were 83 (47%) patients treated at the PRRT-TC, of which 33 (40%) received PRRT prior to chemotherapy and 7 (8%) received temozolomide-containing therapy prior to PRRT. In comparison, 94 (53%) patients were treated at the PRRT-NTC, of which 1 (1%) received PRRT prior to chemotherapy and 0 (0%) received PRRT prior to temozolomide-containing therapy. Conclusions: In this large cohort of metastatic pNET patients, the sequence of chemotherapy and PRRT showed centre-to-centre variability with patients treated at a PRRT-TC being more likely to receive chemotherapy, including temozolomide, prior to PRRT. This may be explained in-part by referral/practice patterns, and PRRT availability. These findings suggest an opportunity to evaluate and optimize the sequence of systemic therapy with the increasing availability of PRRT.
Pathologic exploration of neuroendocrine differentiation in carcinomas.
Authors: Wen Yaru , Shi Susheng 
Published: June 2023

e16238 Background: Tumor with neuroendocrine differentiation (NED) has been verified in non-neuroendocrine organ adenocarcinomas. However, the incidence of NED in various studies varies greatly due to the different selection and criteria of NED markers. Further analysis of large clinical samples is still needed to reveal its biological characteristics and clarify the diagnosis and treatment of NED. Methods: From January 2017 to June 2018，a total of 450 histopathological samples were collected and analyzed retrospectively from patients with multiple malignant cancers, including gastric cancer (GC), colorectal cancer (CRC), lung cancer, breast cancer and prostate cancer treated in Cancer Hospital, Chinese Academy of Medical Sciences. Immunohistochemical staining for NED markers such as synaptophysin (Syn), chromogranin A (ChrA), and neural cell adhesion molecule (CD56) were performed to explore the incidence of different cancer types. Furthermore, NED or non-NED patients were evaluated comparatively in terms of pathological characteristics and prognosis. Results: Up to February 6, 2023, 129 CRC and GC samples were measured. 9 (15.3%) of 59 CRC patients were positive for NED markers, including 7 cases of Syn (+), 6 cases of ChrA (+) and 2 cases of CD56 (+). Moreover, 4 (6.8%) of 59 patients were positive for at least 2 NED markers in CRC. 18 (52.9%) of 34 gastric signer ring cell carcinoma patients were positive for NED markers, including 15 cases of Syn (+) and 14 cases of ChrA (+). Meanwhile, 10 (27.8%) of 36 gastric tubular adenocarcinoma patients were positive for NED markers, including 6 cases of Syn (+) and 10 cases of ChrA (+). Particularly, 17 (24.3%) (11/6, signer ring cell carcinoma/ tubular adenocarcinoma) of 70 GC patients were positive for at least two NED markers. Conclusions: NED is widely present in colorectal cancer and gastric cancer, especially in gastric signer ring cell carcinoma. The encouraging outcomes of the NED prevalence rate may shed light on the individualized treatments for patients with carcinomas. Further explorations are needed in the following research. [Table: see text]
Chromogranin A as surveillance biomarker in patients with carcinoids: CASPAR.
Authors: Meng Qing , Halfdanarson Thorvardur Ragnar , Bornhorst Joshua , Jann Henning , Shaheen Shagufta , Shi Run Zhang , Halperin Daniel M. 
Published: June 2023

e16242 Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare cancers with highly heterogeneous growth rates, yielding very broad ranges of radiographic imaging intervals in standard guidelines, with a multitude of risk for patients. Better tools are needed to reduce risks for these patients. Chromogranin A (CgA) is released by GEP-NET cells and has been associated with increased tumor burden. The European Neuroendocrine Tumor Society (ENETS) considers CgA to be the most practical and useful general serum tumor marker in patients with NETs. However, clinical utility has been limited by the lack of prospective validation studies and by different sensitivity of CgA according to NET tumor type and volume. Accordingly, expert consensus guidelines have offered varying advice regarding the use of CgA to practicing clinicians. The aim was to evaluate the performance of the B·R·A·H·M·S CgA II KRYPTOR immunoassay to monitor the course of disease in patients with well-differentiated GEP-NETs (grade 1 and grade 2). This is the first prospective validation of a clinical algorithm for the interpretation of CgA values in patients with advanced GEP-NETs. Methods: This prospective, multi-center, observational study was designed to validate the performance of the B·R·A·H·M·S CgA II KRYPTOR assay in monitoring disease progression in a defined population of GEP-NET patients with minimal confounding from end organ dysfunction or concomitant medications (e.g. PPIs). Patients were followed for up to 36 months including the evaluation of tumor burden with RECIST 1.1 categorization by imaging (CT/MRI scans). A clinical cut-off for changes in CgA levels over time to indicate the risk that a tumor progression occurred was derived from a retrospective, bicentric observational pilot study. A change in CgA levels between visits was considered positive, if the CgA concentration increased by more than 50% to an absolute value of >100 ng/ml. Results: A total of 175 adult patients were enrolled, and 153 patients had measurable disease at baseline and ≥1 follow-up visit. Using the cut-off for CgA increase defined above resulted in a sensitivity of 34.4% (95%-CI: 25.6% - 44.3%, p < 0.001) and a specificity of 93.4% (95%-CI: 90.4% – 95.5%, p < 0.001). Positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+) and negative likelihood ratio (LR-) to diagnose whether a tumor progression occurred according RECIST 1.1 criteria were 57.9% (95% CI: 45.0-69.8), 84.3% (95% CI: 80.5-87.6), 5.20 (95% CI: 3.23-8.36), and 0.70 (95% CI: 0.61-0.81), respectively. The AUC was estimated at 0.731 (95% CI: 0.670-0.793). Conclusions: B·R·A·H·M·S CgA II KRYPTOR can be used in conjunction with other clinical methods as an aid in monitoring of disease progression during the course of disease and treatment in patients with gastroentero-pancreatic neuroendocrine tumors (GEP-NETs, grade 1 and grade 2).
Clinical and radiological criteria for candidate patients with small bowel neuroendocrine neoplasms (SB-NEN) for minimally invasive surgery: A single-centre experience.
Authors: Guidi Lorenzo , Conti Guglielmo , Bonomi Alessandro Michele , Spada Francesca , Gervaso Lorenzo , Cella Chiara Alessandra , Bertani Emilio , Zugni Fabio , Benini Lavinia , Borghesani Michele , Algeri Laura , Curigliano Giuseppe , Funicelli Luigi , Fumagalli Romario Uberto , Fazio Nicola 
Published: June 2023

e16246 Background: Although open resection represents the standard of care of localized small bowel neuroendocrine neoplasms (SB-NEN), minimally invasive surgery (MIS) has proven to be a viable alternative in patients with low disease burden. This study aims to assess the reliability of preoperative clinical and radiological criteria used at European Institute of Oncology (IEO) to candidate patients with SI-NEN to MIS. Methods: Patients diagnosed with SB-NEN and eligible for MIS at IEO were retrospectively evaluated between 2013 and 2022. Preoperative physical examination, CT enterography (CTE) and Ga68-DOTATOC-PET-CT were used for clinical staging. At IEO NEN multidisciplinary tumor board, the following eligibility criteria were adopted to candidate patients to MIS (curative or palliative): number and localization of primary tumor, grade of superior mesentery artery and vein encasement by lymph-node metastases of 0-2 according IEO criteria (based on Lardiere-Degalte classification). Information on morphology and carcinoid syndrome were collected. The primary endpoint was laparotomy conversion rate. Results: Twelve patients were selected. Patients’ characteristics are available. Median age at surgery was 55 years (range: 33–73). Among these patients, based on pathological findings, 8 (67%) had confirmed nodal involvement, 3 (25%) metastatic disease and 4 (33%) multifocal primary tumor. Vascular involvement (based on IEO criteria) was found in 9 patients (75%). Of note, only 3 (25%) patients had a functioning tumor as a preoperative finding and all tumors resulted well-differentiated. Among 12 patients which underwent laparoscopic surgery, none has been converted to laparotomy surgery. After a median follow-up of 25.3 months (range: 2.5-71.3), the 1-year disease free survival for non-metastatic patients was of 100%. Conclusions: the assessment of tumor burden with 68Ga-PET-CT and CTE according to IEO criteria could be a reliable method to candidate patients affected by SB-NEN to MIS, according to a multidisciplinary approach.[Table: see text]