bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated serum alpha-fetoprotein is a significant prognostic factor for gastric cancer patients: Results based on a large-scale retrospective study.
Authors: Zhan Zhouwei 
Published: June 2022

e16059 Background: To study the clinicopathological features and prognostic factors of serum alpha-fetoprotein (AFP) positive gastric cancer (GC). Methods: A cohort study including 2318 GC patients who underwent radical surgery from January 2008 to December 2015 was retrospectively analyzed. Patients were divided into two groups according to preoperative serum AFP values: 191 patients with AFP-positive GC (AFP > 20ng/mL, 8.24%) and 2127 patients with AFP-negative GC (AFP≤20ng/mL, 91.76%). The clinicopathological features and prognostic factors were explored. Results: Compared with AFP-negative GC, AFP-positive GC had higher rates of liver metastasis, lymph node metastasis, venous invasion, and nerve invasion (all P< 0.05). The 5-year OS, DFS and mLMFS of AFP-positive GC were shorter than AFP-negative GC (55.00% vs. 45.04%, P< 0.001; 39.79% vs. 34.03%, P< 0.001; 13.80 months vs. 16.25 months, P = 0.002). In whole cohort, multivariate analysis found serum AFP levels (positive vs negative), pT stage, pN stage, nerve invasion (yes or no), venous invasion (yes or no) were independent prognostic factors. Serum AFP levels (20-300 ng/mL vs. 300-1000 ng/mL vs. > 1000 ng/mL), pT stage, pN stage, venous invasion (yes or no) were independent prognostic factors in AFP-positive GC. Conclusions: Liver metastases and venous invasion are more likely to occur in AFP-positive GC and lead to poor prognosis. Serum AFP level is an independent prognostic factor in GC patients. As the level of AFP increases, the prognosis becomes worse.
Demographic differences in the treatment of gastric cancer.
Authors: LaPelusa Michael Brian , Shen Chan , Gibson Michael K. , Gillaspie Erin Alexis , Lambright Eric , Chakravarthy Anuradha Bapsi , Eng Cathy 
Published: June 2022

e16078 Background: Globally, as of 2020, gastric cancer is the 5th most common cancer and the 4th common cause of cancer-related death. Our objective is to determine how gender/sex, race, treatment location, and socioeconomic factors contribute to the treatment of patients (pts) with gastric cancer. Methods: 233,479 pts were identified from the National Cancer Database (NCDB) between 2004 and 2018. Pts were divided into 3 age-based subgroups. The <=45 y/o (N=14,481) group was designated early-onset gastric cancer (EOGC). The 46 - 70 y/o (N=118,756) group was termed average-onset gastric cancer (AOGC). The >70 y/o (N=100,242) group was termed late-onset gastric cancer (LOGC). Overall 114,117 (48.9%) received surgery; 112,953 (48.4%) received chemotherapy; and 55,024 (23.6%) received radiation therapy. Unfortunately, data were not available on the receipt of bimodal or trimodal therapy. We used chi-square tests and a logistic regression model to examine factors associated with treatment patterns. Factors considered in the model included: age, gender/sex, race/ethnicity, cancer stage, facility type, year of diagnosis, insurance status, and location of residence. Results: Females represented a higher proportion of EOGC pts (47%) compared to AOGC pts (34.5%) and LOGC pts (41%). A greater amount of EOGC pts were Hispanic (24.9%) compared to AOGC pts (10.4%) and LOGC pts (7.1%). EOGC pts were often treated at academic centers (65.8%) compared to AOGC pts (60.9%) and LOGC pts (54.4%). A larger percentage of EOGC pts were uninsured (11.7%) vs AOGC pts (5.4%) and LOGC pts (0.9%). The table outlines differences in treatment by age, sex, race/ethnicity, facility type, year of diagnosis, insurance, and location of residence (after adjusting for stage). Conclusions: EOGC pts display unique demographic characteristics. After adjusting for stage, significant differences exist in how pts with gastric cancer are treated. Further work is needed to delineate the impact of gastric cancer in young pts and determine which factors play a role in treatment for pts of all ages from both the patient and oncologist perspective.[Table: see text]
Relationship between tumor infiltrating lymphocytes and clinicopathological features in Peruvian gastric cancer.
Authors: Castaneda Altamirano Carlos Arturo , Castillo Garcia Miluska , Bernabe Luis A. , Sanchez Joselyn , Fassan Matteo , Tello Katherine , Chávez Iván , Ruiz Eloy , Barreda Fernando , Valdivia Daniel , Bazan Yaqueline , Abad Milagros , Poquioma Ebert , Montenegro Paola Catherine , Taxa Luis 
Published: June 2022

e16080 Background: Role of tumor-infiltrating lymphocytes (TIL) over clinicopathological features including Mismatch Repair (MMR), HER2 status, Epstein Barr Virus (EBV) and Helicobacter pylori (HP) infection is not well understood in gastric cancer (GC). Methods: TIL level and HP infection was also evaluated in H&E from 503 Peruvian GC patients who underwent surgery. Density of CD3+ T cells, CD8+ cytotoxic T cells, CD163 M2 macrophages, as well as MMR and HER2 status were determined by immunohistochemistry. HP and EBV infection was also detected by qPCR in a 234 cases subset. Results: Median age was 62 years and 50.1% were female, most tumors were grade 3 (59.1%), intestinal subtype (44.8%) and stage III (59.8%). MMR loss was found in 29.4% and HER2+ in 4.7%. HP+ was detected by H&E in 55.7% and by qPCR in 63.7%. EBV+ by qPCR was found in 20.5% and co-infection along with HP in 9.4% (22/234). Stage (p < 0.001), intestinal histology (IH) (p = 0.019), grade (p = 0.006) and lymphovascular invasion (p < 0.001) were associated with longer survival. Median TIL was higher in invasive border (IB) and stromal (ST) than intratumoral (IT) compartment but there were significantly correlated (p < 0.001). High IT TIL was associated with absence of HP H&E (p = 0.009). High ST TIL was associated with older age (p < 0.001), IH (p < 0.001), grade 1 (p = 0.009), lower stage (p = 002), MMR loss (p = 0.019) and EBV+ (p = 0.001). Density of CD3 and CD8 were significantly correlated in IT and ST compartments (p < 0.001). High CD3 density in IT compartment was associated with grade 3 (p = 0.001) and HP- (p = 0.02), and in ST was associated with IH (p = 0.005), grade 1- 2 (p = 0.002) and MMR loss (p = 0.04). High IT CD8 was associated with HER2- (p = 0.016), HP- (p = 0.014) and EBV+ (p = 0.012). High ST CD8/CD3 ratio was associated with diffuse histology (p = 0.034), grade 3 (p = 0.013), more advanced stage (p = 0.022) and recurrence (p = 0.014). High ratio of IT CD8/CD3 was associated with MMR loss (p = 0.007). High ST TIL was associated with longer DFS (p = 0.007). Lower ratio of CD8/CD3 was associated with longer OS (p = 0.024) and DFS (p = 0.02). Conclusions: TIL levels and infiltrating immune subpopulations differs by clinicopathological features in GC including MMR loss, HER2 expression EBV and HP infection. ST CD8/CD3 was associated with recurrence and shorter DFS.
Tislelizumab versus chemotherapy as second-line treatment for advanced or metastatic esophageal squamous cell carcinoma (ESCC, RATIONALE 302): Impact on health-related quality of life (HRQoL).
Authors: Van Cutsem Eric , Kato Ken , Ajani Jaffer A. , Shen Lin , Xia Tianyu , Ding Ningning , Zhan Lin , Barnes Gisoo , Kim Sung-Bae 
Published: June 2022

e16095 Background: RATIONALE 302 was a global phase 3 study (NCT03430843) that investigated tislelizumab (TIS) compared with investigator-chosen chemotherapy (ICC) as second-line treatment for patients (pts) with advanced or metastatic ESCC, in which TIS demonstrated a significant and clinically meaningful improvement in overall survival hazard ratio (HR = 0.70 [95% CI 0.57–0.85], P=0.0001), and a favorable safety profile compared with ICC. Here we assess the HRQoL of pts receiving TIS vs ICC in a pt population that usually experiences HRQoL deterioration. Methods: Adults with advanced or metastatic ESCC whose disease progressed following prior systemic therapy were randomized 1:1 to either TIS 200 mg IV every 3 weeks or ICC (paclitaxel, docetaxel, or irinotecan). HRQoL was measured using the global health status/quality of life (GHS/QoL), physical functioning, and fatigue scores from EORTC QLQ-C30 and the dysphagia, reflux, eating, and pain scores from the EORTC QLQ-OES18 from screening through Cycle 6 or until treatment discontinuation (whichever occurs first). Least-squares mean score change from baseline to Cycles 4 and 6 in HRQoL scores was assessed using a mixed model for repeated measurements. Time to deterioration (TTD) for the GHS/QoL score and the symptom scales of the QLQ-OES18 was examined using the Kaplan-Meier method. Results: Overall, 512 pts (median age 62) were randomized to TIS (n=256) or ICC (n=256). Compared with ICC, TIS-treated pts had stable GHS/QoL and fatigue scores as well as less decline in physical functioning at Cycles 4 and 6 (table). Except for pain, the TIS arm experienced less OES18 symptoms relative to baseline than the ICC arm. TTD analysis showed pts in TIS arm were at lower risk of worsening dysphagia (HR = 0.76 [95% CI 0.53, 1.07], P=0.0562) compared with ICC. Conclusions: The analysis showed that ESCC pts treated with TIS in the second line had a longer maintenance of HRQoL compared to pts treated with ICC. These results, along with improved survival and favorable safety profile, suggest TIS represents a potential new second-line treatment option for pts with advanced or metastatic ESCC. Clinical trial information: NCT03430843. [Table: see text]
Prevalence of MET aberration using next generation sequencing in oncology clinic: A real-world experience.
Authors: Ko Jihoon , Jung Jaeyun , Kim Kyoung-Mee , Kim Seung Tae , Kang WonKi , Lee Jeeyun 
Published: June 2022

e16099 Background: MET has been known as an important therapeutic target in various solid cancer types. With the establishment of next-generation sequencing (NGS) in the oncology clinics, understanding the incidence of MET aberration in patients with metastatic cancer is critical for oncology drug development and efficacy. We investigated MET gene aberration in 2,239 oncology patients who underwent NGS in clinical practice with real-world data. Methods: From Nov. 2019 to Jan. 2021, 2,239 metastatic solid tumor patients who visited oncology clinic were enrolled in the NGS analysis. The NGS panel (TruSight Oncology 500 Assay, Illumina) was over 500 comprehensive sequencing using archival tissue specimen. In addition, PD-L1 22C3 assay results were available in 1,137 patients (50.8%) and 1,761(78.7%) patients had clinical record about 1st chemotherapy for overall survival analysis. Results: 2,239 patients with metastatic solid tumor (37 cancer types) received NGS as part of the clinical practice with an aim to be guided to targeted agents or immunotherapy. The most common cancer types were CRC (N = 702, 31.4%), followed by GC (N = 481, 21.5%), and sarcoma (N = 180, 8.0%). Of 2,239 patients, any MET aberrations (CNVs, fusions, and SNV) were detected in 212 patients. Of the 46 patients with MET amplification, 14 (30.4%) were GC followed by CRC (N = 10, 21.7%), melanoma (N = 7, 15.2%), CCC (N = 6, 13.0%), sarcoma (N = 2, 4.3%), HCC (N = 2, 4.3%), NSCLC (N = 2, 4.3%), pancreatic cancer (N = 2, 4.3%), and gallbladder cancer (N = 1, 2.2%). All MET-amplified tumors had microsatellite stable (MSS) status and 17.4 % patients (N = 8) were TMB-high status. And, 8 of MET-amplified patients concurrently showed MET-positive protein expression by IHC (2+ and 3+). Of note, MET fusion was detected in 0.4% (10 of 2,239) of the patients. The partner gene included ST7, TFEC, LRRD1, CFTR, CAV1, PCM1, HLA-DRB1 and CAPZA2. In survival analysis, patients having MET amplification or fusion had shorter OS and PFS than the others, suggesting MET aberration was an important key factor that could determine final response results to current chemotherapy. Conclusions: Based on our comprehensive NGS survey focused on MET aberration, we identified approximately 2.1% MET amplification and 0.4% MET fusion in patients with metastatic solid tumors. They showed worse response after chemotherapy and shorter OS and PFS.
Multi-omics analysis of locally advanced esophageal cell squamous carcinoma treated with radio-chemotherapy.
Authors: Li Hongwei , Li Jing , Zhang Xiaqin , Liang Hua , Ji Liyan , Gao Xuan , Xia Xuefeng 
Published: June 2022

e16106 Background: The incidence rate of esophageal cell squamous carcinoma (ESCC) increases every year worldwide. Although the molecular characteristics of locally advanced esophageal carcinoma have been extensively studied, TCR evolution dynamics before and after treatment in patients with ESCC undergoing radical radiotherapy and chemotherapy are unknown. Methods: In this study, we performed whole-exome sequencing (WES) and RNA sequencing (RNA-seq) on tumor tissues from 11 ESCC patients who received radiotherapy and chemotherapy. T cell receptor (TCR) sequencing was performed in 33 ESCC blood samples, which included three time points: pre-treatment, on-treatment and post-treatment. We compared TCR clonality and Shannon index among the pre-treatment, on-treatment and post-treatment ESCC patients using paired samples Wilcoxon test. The t test was uesd for statistical analysis comparing the clonality and clonal frequency between patients with mutant and wild-type gene. Results: The median TMB is 3.32 mutations/Mb (range 1-6 muts/Mb). We identified nine significantly mutant genes including TP53 (100%), MUC17 (55%), FLG (45%), FLG2 (36%), FOXN1 (27%), HIST1H1E (18%), VN1R1 (18%), RIPK3 (9%), and ZNF628 (9%). Clonality was significantly increased from pre-treatment to post-treatment (p = 0.008) and from on-treatment to post-treatment (p = 0.04). Two patients exhibited an continuous increase of TCR CDR3 (CHCLPAED_AGGGELFF) frequency in post-treatment compared to on-treatment patients. Three patients had elevated level of CDR3 amino acid sequence (CASSLDSNQPQHF) after treatment. To explore the effect of the mutant gene on the TCR clonal pattern, we found that the baseline clonality and clonal frequency in mutant FAT1 (MUT) were significantly lower than that in wild-type (WT) patients (p = 0.044 and p = 0.013, respectively), while they were not significant after treatment between FAT1-MUT and WT patients. Intriguily, in FAT1-MUT patients, the clonality and clonal frequency underwent therapy were higher than that at baseline. The results suggested that the FAT1-MUT patients might be sensitive to treatment and FAT1 might contribute to immune response upon radio-chemotherpay. During radio-chemotherapy, the clonality and clonal frequency in INTS1-MUT and LCT-MUT patients had the similar phenomenon to the FAT1-MUT patients. Interestingly, a higher clonal frequency was observed after radiotherapy and chemotherapy than that of pre-treatment (p = 0.0086) in patients with mutant KMT2D (an epigenetic modifier coding lysine methyl transferase 2D). Conclusions: TCRs is clonal expansion after radiotherapy and chemotherapy in ESCC, suggesting an immune-activated microenvironment after radio-chemotherapy. Our multi-omics analysis provided the basic TCRs dynamics and its genomic and epigenomic association during the radio-chemotherapy of esophageal cell squamous carcinoma.
Non-hepatocellular carcinoma management: A SEER database analysis.
Authors: Legenza Ashton , Tupper Connor , Burdyny Michael , Silberstein Peter T. 
Published: June 2022

e16108 Background: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, however, chronic viral hepatitis and cirrhosis place patients at an increased risk for non-HCC malignancies as well. A major treatment option for these tumors is local tumor destruction via a number of minimally invasive techniques available to interventional radiologists. This study assessed the prognostic impact of various liver-directed local tumor therapies in the management of non-HCC liver cancer. Methods: We searched the SEER-18 database for malignant liver cancers not coded as HCC (8170-8175) that were diagnosed between 2000-2018. Patients were excluded if the cause of death was not associated with their cancer according to SEER’s cancer-specific death categorization. The SEER database tracks survival up to 60 months. SPSS was used for all descriptive and univariate survival statistics. Results: A total of 228 patients were collected from this search. 59.6% of cases were from males and the average age was 64 years old (median = 65). 60.1% were in non-Hispanic White patients, followed by Hispanic (16.2%), non-Hispanic Asian or Pacific Islander (14.0%), and non-Hispanic Black (9.2%) patients. Of the 170 patients with staging coded, 62.9% were local, 24.7% were regional, and 12.4% were distant. 36.8% of patients received some form of chemotherapy, while only 3.1% received radiation. When grouped by age range (< 49, 50-69, 70+), survival did not differ between groups. Sex also did not influence survival (p = .325). Patients that received chemotherapy had worse outcomes, likely due to worse staging which was negatively associated with survival (p < .05). Radiation did not significantly improve survival. Of the local tumor destruction therapies, Heat-Radio-Frequency ablation (RFA) (n = 150) improved survival significantly in comparison to: local tumor destruction not otherwise specified (n = 42), photodynamic therapy (n = 1), electrocautery (n = 4), cryosurgery (n = 4), and ultrasound or acetic acid (n = 15) (all p < 0.05). Laser surgery (n = 3) and intratumoral injection of alcohol (n = 9) had no significant outcome differences. RFA had an estimated mean survival time of 35.7 months while all other interventional radiology modalities combined had a mean estimated survival time of 21.4 months (p < .000). Conclusions: Though limitations of a small sample size and univariate statistical analyses were present in this study, RFA likely has improved survival compared to other interventional radiology modalities used in the treatment of non-HCC liver cancer.
Factors affecting outcomes in gallbladder cancer: A single institution retrospective analysis.
Authors: Hatic Haris , Li Peng , Paluri Ravi Kumar 
Published: June 2022

e16109 Background: Gallbladder cancer is one of the highest fatal malignancy. We conducted a retrospective analysis to study the outcomes of gallbladder malignancy in an academic care setting. Methods: Data was collected retrospectively on patients treated at University of Alabama at Birmingham between January 2005 and June 2015 from the electronic medical record using a standardized data collection tool (Redcap). We evaluated for predictors of overall survival (OS) and progression-free survival (PFS). Results: Of the 93 patients in this study, 66% were female. Adjuvant chemotherapy (CT) was given to 11% and adjuvant chemoradiation (CRT) to 14%. On multivariate analysis, albumin > 3.5, uninvolved margins, absence of lymphovascular/peri-neural invasion were independent predictors of OS and PFS (Table). The overall median survival was 24.3 months with a 5-year median OS at 23.7%. Surgery with CRT for the full cohort had a median OS of 54.4 vs 15.6 (p = 0.0048) months compared to surgery CT alone. The OS in stage 3-4 patients with surgery alone vs surgery & CT was 5.5 versus 28.7 months respectively (p = 0.0052). The PFS for the same group was 17.5 vs 4.6 months (p = 0.0052). Conclusions: The dismal survival rates of gallbladder cancer made. adjuvant therapy (CT or CRT) critically important. Concurrent chemoradiation needs to be evaluated in randomized clinical trials for potential improvement in clinical outcomes compared to currently approved standard of care, adjuvant CT alone. [Table: see text]
A retrospective study on the efficacy and safety of regorafenib or regorafenib combined with immune-checkpoint-inhibitors (ICIs) after first-line therapy in patients with advanced hepatocellular carcinoma.
Authors: Yan Tao , Peng Caiyun , Yu Lingxiang , Duan Xuezhang , Ji Dong , Zhang Linzhi , Cheng Jiamin , Wu Tong , Su Guodong , Jing Yi , Li Yinyin , Lu Yinying 
Published: June 2022

e16115 Background: The efficacy of first-line ICIs combination therapy patients with advanced hepatocellular carcinoma (HCC) was better than that of TKIs alone. This study was conducted to explore whether regorafenib combined with ICIs has better efficacy in second-line therapy. Methods: This retrospective study included 101 patients who have received regorafenib after the failure of at least one molecular-targeted therapy evaluated between March 2017 to November 2021. The patients were divided into two groups based on receiving regorafenib (cohort A) or regorafenib combined with ICIs(cohort B). The primary endpoint was Progression-Free Survival (PFS), and the secondary endpoints included the Objective Response Rate (ORR), Disease Control Rate (DCR), Overall Survival (OS), and safety. Results: 29 patients were in the cohort A and 72 were in the cohort B. There were no significant differences in age, gender, weight, ECOG performance status, Child-Pugh, BCLC staging, and the proportion of previous therapy regimens between the two cohorts. Among them, the first-line therapy mainly includes sorafenib, lenvatinib with or without ICIs. The median PFS (4.0 months), 6 months PFS rate (25.66%) and DCR(65.52%) of cohort A were poor than that of cohort B (8.7 months, 83.33%, 74.13%), (P＜0.05). OS data was not yet available. First-line therapy, use of TKI with ICIs (n = 31) or TKI without ICIs(n = 27) (PFS 8.70m VS 8.37m，P = 0.84), use of sorafenib with or without ICIs (n = 22), or lenvatinib with or without ICIs (n = 33)(PFS 8.87m VS 7.60m，P = 0.77), didn’t affect the PFS and ORR of the later line therapeutic regimens. In the cohort B, the ORR of the second-line (29.31%) was better than that of the third-line (0), (P = 0.03). Adverse events (AEs) of all grades were statistically different between the two groups (P = 0.03), but there was no significant difference in the incidence of grade 3-4 AE. Conclusions: In the later-line therapy, regorafenib combined with ICIs therapy showed better curative effect, especially in the second-line. Regorafenib combined with ICIs is recommended as early as second-line therapy to benefit patients. Different regimens of first-line therapy have no effect on PFS in second-line therapy.[Table: see text]