bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a postoperative nomogram to predict disease-specific mortality in gastric cancer: A competing risk analysis using variables the AJCC recommends be collected and registered.
Authors: Bando Etsuro , Ji Xinge , Kattan Michael W. , Koseki Yusuke , Furukawa Kenichiro , Fujiya Keiichi , Tanizawa Yutaka 
Published: June 2023

e16099 Background: The American Joint Committee on Cancer (AJCC) has increasingly recognized the need for individual risk prediction model for the era of tailored therapy. In several reports, gastric cancer postoperative nomograms for predicting overall or disease-specific survival have been described. The AJCC Precision Medicine Core introduced the attractiveness of disease-specific mortality (DSM) as an endpoint of risk model. This study aimed to develop the first pretreatment gastric cancer postoperative nomogram for predicting DSM that considers competing risks (CRs). Methods: The nomogram was developed using data of 2,501 patients with primary gastric cancer who are potential candidate for adjuvant chemotherapy based on NCCN guideline, and it was created with a multivariable Fine and Gray subdistribution proportional hazard regression model. Fifteen pathological or non-tumor-related variables (age, sex tumor location, tumor size, macroscopic type, histology, depth (pT), number of positive nodes (pN), number of negative nodes, location of positive nodes, lymphovascular invasion, lavage cytology (CY), tumor margin, serum CEA and serum CA19-9) were collected. They are recommended to collect and register by the AJCC. The model was validated internally using measures of discrimination (Harrell’s C-index), calibration and decision curve analysis. Results: In the development procedure, multivariable analysis for DSM selected 12 variables (age, tumor location, macroscopic type, histology, pT, pN, number of negative nodes, location of positive nodes, lymphovascular invasion, CY, tumor margin and serum CEA) for constructing the nomogram. The developed nomogram showed good discrimination, with a C-index of 0.802(0.786-0.817) that of the American Joint Committee on Cancer (AJCC) pathological stage was 0.714 (0.697-0.734). The calibration appeared to be accurate for the 5-year prediction. Compared with scenarios in which no prediction model was used for postoperative treatment decision making (i.e., assume all or assume none), the nomograms had a favorable net benefit across a wide range of decision threshold probabilities between 5-year DSM probabilities of approximately 5 and 95%. Conclusions: This new postoperative risk model accurately predicts DSM in gastric cancer and can be used for patient counseling in clinical practice.
Development of a plasma biomarker panel for gastric cancer detection based on an autoimmune response signature.
Authors: Dou Rongzhang , Irajizad Ehsan , Cai Yining , Fahrmann Johannes , Vykoukal Jody , Katayama Hiroyuki , Chen Yihui , Abdel Sater Ali Hussein , Pizzi Melissa , Ostrin Edwin J. , Yamashita Kohei , Ajani Jaffer A. , Hanash Samir M 
Published: June 2023

e16101 Background: Gastric cancer is frequently diagnosed at an advanced stage and is associated with poor outcomes. A humoral immune response to tumor antigens in the form of autoantibodies occurs early during tumor development. Harnessing autoantibodies and corresponding antigens has potential for diagnostic and therapeutics applications. Methods: Plasma samples from gastric cancer patients were collected before treatment and from non-gastric cancer cases and healthy controls for identification and quantitative analysis of immunoglobin (Ig)-bound antigens using mass spectrometry. The Ig-bound antigens were pulled down with a Protein A/G column for analysis by mass spectrometry. A protein A/G plate capture enzyme-linked immunosorbent assay (ELISA) was developed to validate Ig-bound MS results. A combined biomarker panel was established based on a logistic-regression model and ROC analysis was used to assess panel performance. Results: From a total of 983 proteins identified from gastric cancer samples, four Ig bound proteins were found to be enriched in gastric cancer plasmas compared with healthy controls and plasmas from other cancer types which yielded an area under the curve (AUC) of 0.973 (95% confidential interval [CI] = 0.92-1.00) for gastric cancer discrimination with a sensitivity of 0.91 at 95% specificity. Enzyme-linked immunosorbent assay (ELISA) based data yielded a high correlation (r = 0.72, P = 0.0199) with Ig-bound mass spectrometry data. These four proteins were found to be highly expressed in gastric cancer based on TCGA transcriptomic data with concordant tumor cell proteomic data. Conclusions: Our data reveal a panel of plasma Ig-bound antigens associated with the development of gastric cancer with potential application for gastric cancer detection and monitoring and potential therapeutic relevance.
Early onset gastric cancer: An analysis of epidemiological and environmental risk factors.
Authors: Zarrinkhoo Erfan , Condamoor Shreya , Klingbeil Kyle D. , Park Joon , Jackson Nicholas , Chiu Victor Yundeh , Kadera Brian E. 
Published: June 2023

e16103 Background: Gastric cancer is the fourth most common malignancy in the world and the second leading cause of cancer related deaths. Its overall incidence has decreased in recent years, but recent data suggests that its rate has actually been increasing specifically amongst younger adults. Emerging data suggests that it is the combination of biological risk factors and environmental triggers that are the cause for this increasing rate. There has been increased interest in studying early onset gastric cancer (EOGC) as a proxy for understanding the genetic alterations that lead to gastric cancer at any age. However, understanding the environmental factors that lead to the development of cancer at a younger age is an area of study that requires more exploration. In this study, we investigate the epidemiology, environmental risk factors and common presenting symptoms associated with early onset gastric cancer patients. Methods: This is a retrospective cohort study of 174 patients with newly diagnosed gastric adenocarcinoma at three safety net hospitals in Los Angeles between 2010 and 2022. The patients were divided into two groups, with an age cutoff of 45 years old for early onset gastric cancer. We compared the rates of smoking, alcohol use, infection with H pylori and gender between the two groups. The stage at time of presentation, rates of misdiagnosis, presenting symptoms, and mortality rates were also compared. Results: There was no statistically significant difference (p < 0.05) in rates of smoking, alcohol use, and H. pylori infection between the groups. However, patients with early onset gastric cancer were 10% more likely to be misdiagnosed, and 6% more likely to present with metastatic disease. They were also 16% more likely to be female, 17% more likely to be Hispanic, and 22% more likely to expire compared to patients older than 45. An analysis conducted on patients’ presenting symptoms indicated that hematemesis was much more likely to be associated with patients less than 45 to a statistically significant level (p = 0.035). Conclusions: Based on our findings, EOGC was more likely to be seen in females and Hispanic populations. Additionally, no risk factors were identified to be more closely associated with either cohort. EOGC patients were more likely to be misdiagnosed and therefore present with advanced disease, leading to higher rates of mortality. Further investigation into both genetic alterations and environmental factors associated with early onset gastric cancer is warranted, as this holds important implications for patients regarding diagnosis, treatment, and overall outcomes.
Donafenib combined with anti-PD-1 antibody and transarterial chemoembolization (TACE) as first-line (1L) treatment for unresectable/advanced hepatocellular carcinoma (HCC).
Authors: Zhou Jian , Yan Zhiping , Wang Zheng , Qiu Shuang-Jian , Yang Minjie , Zhu Kai , Yi Yong , Yu Lei , Sun Yun-Fan , Zhang Bo , Yu Jiaze 
Published: June 2023

e16107 Background: Targeted drugs, immune checkpoint inhibitors and TACE are important non-surgical approaches to treat HCC. A triple combination of the three is under investigation. This prospective study was conducted to assess the efficacy and safety of donafenib combined with anti-PD-1 antibody and TACE as first-line treatment for unresectable or advanced HCC. Methods: Patients (pts) who had histologically or clinically confirmed HCC and with no prior systemic therapy, at least one measurable lesion per mRECIST, Child-Pugh score ≤7, and ECOG PS score 0-1 were enrolled and received donafenib 100 mg twice daily, anti-PD-1 antibody Q3W and on-demand conventional TACE. CT/MRI scans were performed every six weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival and safety. Results: A total of 30 pts were enrolled between Dec 2021 and Nov 2022. All pts had HBV-related HCC and baseline ECOG PS score of 0. Baseline characteristics are shown in the Table. As of 6 Feb 2023, eleven pts had discontinued the triple therapy. The median follow up time was 3.6 months (range, 1.8-13.4). The median number of on-study TACE sessions was 2 (range, 1-4). Among 29 efficacy evaluable pts, five pts had disease progression and no death occurred. The median PFS was not reached (95%CI, 2.4 months -NE). The 6-month PFS rate was 69.4% (95%CI, 34.5%-84.0%). Five pts had a complete response and 13 had a partial response (responders). ORR and DCR were 62.1% (95%CI, 42.3%-79.3%) and 86.2% (95%CI, 68.3%-96.1%) per mRECIST. The median time to response was 1.3 months (95%CI, 1.1-1.6). The median duration of response was not reached (95%CI, 3.4 weeks-NE). Four pts (1 with BCLC B, 3 with BCLC C) underwent successful surgical resection after a median treatment duration of 2.9 months (range, 1.8-3.3) and no recurrence was noted with a median of 5.9 months (range, 2.8-10.2) follow-up after hepatectomy. In the safety population (n = 30), any grade and grade 3 treatment-related adverse events (TRAEs) occurred in 15 (50.0%) and 7 (23.3%) pts with no grade 4 TRAEs or toxic death. Rash was the most common grade 3 TRAE (incidence: 13.3%) and led to treatment discontinuation in one pt. Conclusions: The triple combination of donafenib plus anti-PD-1 antibody and TACE showed promising efficacy and was well tolerated in pts with unresectable or advanced HCC. Clinical trial information: NCT05262959 . [Table: see text]
Costs and health care resource utilization (HCRU) for patients with advanced biliary tract (aBTC) cancer using administrative databases in Ontario, 2010 to 2020.
Authors: Seung Soo Jin , Saherawala Hasnain , Syed Iqra A. , Clouthier Derek L. , Shephard Cal S. , Chen Eric Xueyu 
Published: June 2023

e16112 Background: Gemcitabine and cisplatin (gemcis) has been the standard of care for biliary tract cancer (BTC) for over a decade. One US model predicted the total lifetime cost of gemcis per patient to be $54,077 in 2020 CAD, although not all costs were considered. Our study objectives included quantifying updated costs and health care resource utilization (HCRU) associated with advanced BTC using real-world, population-level data from Ontario databases. Methods: We conducted a retrospective population-level study of patients diagnosed with recurrent or unresectable/advanced BTC (gallbladder cancer [GBC], intrahepatic and extrahepatic cholangiocarcinoma [IHC and EHC], Ampulla of Vater [AoV]) between January 1, 2010 and December 31, 2019. Follow-up data were available until December 31, 2020. HCRU and costs were calculated from the start date of first line (1L) of BTC-specific systemic therapies to death or the end of March 31, 2020 whichever occurred first. A macro-based costing methodology (GETCOST) was used and the mean cost per patient was reported in 2020 Canadian dollars (CAD). Mean cost per patient was calculated from diagnosis till the end of follow-up or death. The total number of HCRU-specific encounters for all years was divided by the number of BTC patients who used that HRCU in order to report the mean number of HCRU encounters (e.g., cancer clinic visits and inpatient hospitalizations). Results: Of 2,142 advanced BTC patients identified, 1,968 were diagnosed with non-AoV cancers (GBC, IHC, EHC or general BTC not otherwise specified) and 174 patients were diagnosed with AoV cancer. The mean cost per patient for all 1L-treated patients was $36,662 ($36,378 for non-AoV compared to $40,092 for AoV patients). By 1L-specific therapies, the highest mean cost per patient was for patients on gemcitabine and taxane combinations (gemtaxane) at $44,190, followed by gemcitabine and cisplatin (gemcis) at $34,507, then FOLFOX or FOLFIRI (fol) at $39,002 and carboplatin and gemcitabine (gemcarb) at $30,905. Untreated patients had a mean cost per patient of $42,136. The mean number of cancer clinic visits per patient per year during 1L ranged from 9.7 (untreated) to 13.7 (gemcis), while the inpatient hospitalizations per patient per year during 1L ranged from and 1.5 (gemcarb, fol and gemtaxane) to 2.4 (untreated). Conclusions: This study reports Canadian-specific, real-world costs and HCRU results of over 2,000 BTC patients. While cost results were stratified by type of BTC (AOV and non-AOV) and type of 1L therapies, the mean cost per patient ranged from $30,905 CAD to $44,190 CAD and HCRU results indicated substantial mean number of cancer clinic visits and inpatient hospitalizations. Thus, BTC patients incur a significant economic burden to the patients and Ontario public payer health system.
Regorafenib in patients (pts) with unresectable hepatocellular carcinoma (uHCC) in real-world practice in the United States (US): Final analysis of the prospective, observational REFINE study.
Authors: Kaseb Ahmed Omar , Cabrera Roniel , Iyer Renuka , Parikh Neehar , Kalman Richard , Ozgurdal Kirhan , Khan Javeed , Babajanyan Svetlana , Finn Richard S. 
Published: June 2023

e16114 Background: In the observational REFINE study of regorafenib (NCT03289273) in pts with uHCC, treatment-emergent adverse events (TEAEs) were consistent with those reported in the global, phase 3 RESORCE trial (YJ Kim, ILCA 2022). Median overall survival (OS) in the overall global cohort of REFINE was 13.2 months; here, we present the final analysis of the US pt cohort. Methods: REFINE was an international, prospective, multicenter study that enrolled pts with uHCC for whom a decision to treat with regorafenib was made by the treating physician prior to enrollment, according to the local health authority approved label. The primary objectives were safety, including incidence of TEAEs (MedDRA v25) and dose modifications due to TEAEs. Secondary endpoints included OS, progression-free survival (PFS), and duration of treatment (DoT). Results: Of the 1005 evaluable pts from the global cohort, 65 pts (6%) were from the USA. In the US cohort, 78% were male, 69% had ECOG PS 0/1, and the population was younger than the global cohort (54% were aged <65 years vs 45% in the global cohort). The most common HCC etiology was hepatitis C in the US cohort (52% vs 24% in the global cohort) and the second most common was alcohol use (34% vs 25% in the global cohort). A lower proportion of US pts had extrahepatic spread compared with the global cohort (48% vs 59%), while a similar proportion had vascular invasion (both 34%). Use of prior immune checkpoint inhibitors was more frequent in US pts than in the overall global cohort (25% vs 10%). Most US pts (88%) had received prior sorafenib, consistent with the global cohort (96%). However, a relatively lower proportion of pts received regorafenib as a second-line therapy (71% vs 84% in the global cohort). Transarterial chemoembolization was the most common prior non-systemic treatment (42%). Median DoT was 3.1 months (range <0.1–24.6 months) in US pts vs 3.7 months (range <0.1–38.9 months) in the global cohort. TEAEs were reported in 91% of US pts and apart from a lower incidence of diarrhea and hand–foot skin reaction (HFSR) in US pts, incidences of TEAEs were comparable to the global cohort. In addition, TEAEs resulting in dose modification were relatively lower in US pts (38% vs 45% in the global cohort). Median OS in US pts was 11.4 months (95% CI 8.4, 18.0), similar to that reported for the global cohort (median OS 13.2 months [95% CI 11.6, 14.8]). Conclusions: The REFINE real-world study confirmed the safety and effectiveness of regorafenib in a broader population of pts than in the RESORCE trial. The findings remained consistent in US pts with uHCC. Clinical trial information: NCT03289273 . [Table: see text]
Clinical efficacy and safety of regorafenib for patients with recurrent hepatocellular carcinoma after hepatectomy: A real-world study in China.
Authors: Ni Yanbin , Zheng Jiaxi , Wang Yang , Li Zhao , Zhu JiYe , Gao Jie 
Published: June 2023

e16119 Background: The therapeutic strategy for recurrent hepatocellular carcinoma (HCC) after hepatectomy is limited. There is a significantly unmet clinical need for effective treatment options for these patients. This study aimed to assess the clinical efficacy and safety of regorafenib alone or combined with a PD-1 inhibitor as a second or further-line treatment for patients with recurrent HCC after hepatectomy. Methods: Patients receiving regorafenib alone or combined with a PD-1 inhibitor in Peking University People’s Hospital from January 2019 to November 2022 were entered prospectively into a clinical database. Data were retrospectively analyzed. The major inclusion criteria were: histologically confirmed diagnosis of HCC; disease recurrence after radical hepatectomy; with tumor that cannot be re-resected; ECOG performance status score (PS) ≤2. Regorafenib was administered at the daily dose of 80-120 mg for more than 4 weeks. Progression-free survival (PFS) was the primary endpoint. The second outcomes included PFS, objective response rate (ORR), disease control rate (DCR), and the incidence of drug-related adverse events (AEs). CTCAE v5.0 was used for evaluation of AEs. Results: Twenty-two patients were enrolled with a median age of 59. The hepatic function of all patients was mildly impaired (Child-Pugh A). Among all patients, 36.35% of cases were enrolled in Barcelona Clinic Liver Clinic (BCLC) A and the remainder were in BCLC B. Eight cases (36.36%) received regorafenib in combination with PD-1 inhibitor therapy and 14 cases received regorafenib treatment alone. Among all patients, 86.36% of the cases were treated with regorafenib as second-line therapy. Five patients (22.73%) had extrahepatic metastasis. The median PFS and overall survival (OS) were 11.66 (±10.20) months and 16.92 (±10.21) months, respectively. The 3-month PFS rate was 100%. The 6-month and 12-month PFS rates were 75% (95%CI: 58.49%-96.70%) and 53.33% (95%CI: 34.88%-81.50%), respectively. The results showed a significant difference in median PFS between patients receiving regorafenib as second-line therapy and third-line therapy [12.30 months (95%CI: 4.25-20.36) vs 4.30 months (95%CI: 3.50-5.10); P<0.001]. In addition, there is a significant difference in median PFS between patients with extrahepatic metastasis and those without extrahepatic metastasis [5.20 months (95%CI: 3.48-6.92) vs 18.20 months (95%CI: 5.09-31.31; P=0.003)]. The ORR and DCR were 18.18% and 81.82%. The most frequent AEs were hand-foot syndrome (40.91%), pain (18.18%), diarrhea (13.64%), and hypertension (13.64%). Most AEs were grade 1 or 2, with only 1 case having grade 3 AE. Conclusions: Regorafenib alone or combined with a PD-1 inhibitor showed significant clinical efficacy in controlling the disease progression of recurrent HCC.
Efficacy and safety of donafenib combined with transcatheter arterial chemoembolization (TACE) and anti-PD1 antibody for the treatment of unresectable hepatocellular carcinoma (uHCC): A retrospective study.
Authors: Ge Naijian , Wang Xiangdong 
Published: June 2023

e16120 Background: For unresectable hepatocellular carcinoma (uHCC), the efficacy of TACE monotherapy is not satisfactory. It has recently been reported that molecular targeted drugs combined with anti-PD1 antibody and TACE exhibit improved anti-tumor efficacy compared with monotherapy. Donafenib is a new generation of multi-kinase inhibitor which is approved as the first-line treatment for uHCC. This study aimed to explore the efficacy and safety of the combination therapy of donafenib, anti-PD1 monoclonal antibody and TACE in patients with uHCC. Methods: This was a single-center retrospective study, and involved patients with uHCC who received donafenib (200 mg po bid) combined with TACE and anti-PD1 monoclonal antibody or donafenib (200 mg po bid) combined with TACE at Shanghai Eastern Hepatobiliary Surgery Hospital from September 2021 to September 2022. All patients had at least one measurable lesion defined by mRECIST criteria. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) data of patients were collected and analyzed. Results: A total of 34 patients with uHCC were included and had a median age of 56 years (32–81 years). Of these patients, 3 (9%) were classed as BCLC stage B, 31 (91%) were BCLC stage C. All 34 patients were complicated with HBV infection. First-line treatment was administered to 24 patients (71%), among which 21 patients received donafenib combined with TACE and anti-PD1 antibody. 3 patients were treated with donafenib combined with TACE. The remaining 10 patients (19%) received second-line treatment, among which 7 patients were treated with donafenib combined with TACE and anti-PD1 antibody. 3 patients received donafenib combined with TACE. There were 14 patients (41%) with baseline AFP ≥400 ng/mL. At data cut-off, the median follow-up time was 5 months [95% CI: 3.42-6.58]. The best overall response rate (BOR) was complete response in 5 patients (14.7%), partial response in 13 patients (38.2%), stable disease in 10 patients (29.4%), and progressive disease in 6 patients (17.6%). The ORR was 52.9% (95%CI: 36.7–68.6%) and DCR was 82.4% (95%CI: 66.5–91.7%). The median PFS and median OS were not reached, the one-year PFS rate was 61.6% (95%CI: 38–78.7%), and the one-year OS rate was 83.1% (95%CI: 56.1–95.2%). The ORR (58%) and DCR (87.5%) of patients receiving first-line treatment were better compared with those of patients receiving second-line treatment (40% and 70%, respectively). Treatment-related adverse events (TRAE) were reported by 30 patients (88.2%), of which 7 patients (20.6%) had grade 3 TRAE. No grade 4 or 5 TRAE was reported. Conclusions: Donafenib combined with TACE and anti-PD-1 antibody exhibited encouraging efficacy and favorable safety profile in patients with uHCC.