bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regorafenib plus PD-1 inhibitors in Chinese patients with microsatellite stable/mismatch repair proficient metastatic colorectal cancer: A real-world study.
Authors: Yang Kaili , Han Lu , Zhao Yun-Bo , Ge Yang , LI Qin , Wang Yusheng , Wu Shikai , Zhang Yan , Zhao Chuanhua , Zhou Jing , Zhao Lin 
Published: June 2021

e15585 Background: A previous phase 1b trial has shown encouraging efficacy of regorafenib plus nivolumab in patients with microsatellite stable/mismatch repair proficient (MSS/pMMR) metastatic colorectal cancer (mCRC). We aimed to evaluate the efficacy and safety of this regimen in Chinese patients in the real world. Methods: We retrospectively identified patients with MSS/pMMR mCRC who received at least one dose of programmed cell death-1 (PD-1) inhibitors plus regorafenib from 5/2019 to 2/2021 in 10 Chinese medical centers. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and the safety. Results: Fifty-two patients were identified. Liver metastases were presented in 35 patients (67%). A total of 48 patients (92%) received regorafenib plus a PD-1 inhibitor as the third or later line treatment. At the data cut-off, 11 patients (21%) were still on treatment. Other patients terminated treatment because of progressive disease (45%), treatment-related adverse events (TRAEs) (14%) or treatment-unrelated deaths (6%). The median treatment cycle was 3 (range, 1-18). At a median follow-up of 4.9 months, the median OS was 17.3 months (95% CI, 10.2-NR) and the median PFS was 3.1 months (95%CI, 2.5-6.0). Baseline liver metastases were associated with inferior PFS (2.7 versus 6.3 months, p <0.05), but not OS (17.3 months versus NR, p =0.6). Among 38 patients evaluable for response, two patients (5%) achieved partial response, and 17 patients (45%) experienced stable disease as the best response. The DCR was 50% (95%CI, 5.0-NR) and was similar among different PD-1 inhibitors (Table). TRAEs were observed in 30 patients (58%). Fatigue (21%), hand-foot syndrome (19%) and rash (13%) were the most common TRAEs. Eight patients (15%) experienced grade 3-4 TRAEs, including rash (n=3), hand-foot syndrome (n=2), hypertension (n=1), myocardial enzyme elevation (n=1) and visual field loss (n=1). No treatment-related death occurred. Conclusions: The combination of regorafenib plus PD-1 inhibitors was generally tolerated and exhibited potential benefit in terms of OS and DCR. The presence of baseline liver metastases was predictive for shorter PFS but requires further investigation. Disease control rate of different PD-1 inhibitors.[Table: see text]
Demographic differences of colorectal cancer in the community and academic setting in patients over the age of 75 compared to those aged 50 to 75.
Authors: Busari Kafayat Adebukola , Williams Renee , Huston Jamie , Stewart Oliver , Gachette Darrel , Meredith Kenneth Lee 
Published: June 2021

e15594 Background: The age of life expectancy in the United States is 78.9 years of age and continues to increase with the help of public health initiatives along with scientific and technological breakthroughs in medicine. However, colorectal cancer screening guidelines for those over age 75 are individualized and not recommended in those over 85. We aimed to investigate the demographic differences of colorectal cancer by sex and race in patients aged 75 vs those aged 50-75, in the community and academic practice. Methods: Data were analyzed from the National Cancer Database between 2010-2014. Results were divided into two categories (50-75 year old, >75 year old) and included number of patients, sex and race. Patient characteristics were compared with Mann-Whitney U, Pearson’s Chi-square, and the Kaplan-Meier method. Data was further analyzed comparing sex and race using chi-square analysis. Results: 167, 059 patients were included in the analysis. 49,551 cases identified in the academic practice and 117, 508 in the community practice. In the academic practice, group A (age 50-75), 57.3% (20,810) were male vs. 42.7% (15,488) female. In community practice, group A, 56.5% (43, 915) were male vs 43.5% (33, 742) female (p-value <0.05). Conversely, in the academic practice-group B (age >75), 46.2% (6127) were male vs 53.8% (7126) female. In the community practice-group B, 55.3% (22,027) were female vs 44.7% (17,824) male; (p-value <0.05).For Black patients, decline in cases is seen by age. In academic practice, 16.5% of cases were aged 50-75 vs. 11.9% over age 75. In community practice; 11.5% were aged 50-75 vs. 6.5%, p<0.05). Comparatively there was an increase in cases in White patients by age diagnosed in academic and community practice; 77.5% vs 84.2 in 50-75 and 84.8 vs. 90.9% in >75, respectively (p<0.05). Conclusions: Women age >75 comprised a statistically significant greater proportion of colorectal cancer cases compared to men age >75 in both the community and academic setting. Contrary to established reports detailing higher incidence rates in males aged 50-75. Furthermore, there is an increase in cases with age in White patients in comparison with a decrease in cases in Black patients. These findings may suggest the need for a more universal and less individualized approach for individuals over age 75.
Comparison of colorectal cancer location and metastasis site in patients aged 50 to 75 versus age 75 and older in community and academic practice.
Authors: Busari Kafayat Adebukola , Williams Renee , Huston Jamie , Gachette Darrel , Stewart Oliver , Meredith Kenneth Lee 
Published: June 2021

e15595 Background: Current guidelines recommend cessation of average risk colorectal cancer screening at age 75, after which a more individualized approach is endorsed. There is limited data on characteristics of colorectal cancer in patients over the age of 75. We aimed to determine if colorectal cancer site and metastasis is greater in the community vs academic setting in patients aged 50-75 compared to those age 75 or older. Methods: Data were analyzed from the National Cancer Database (NCDB) between 2010-2014. Results were divided into two categories (50-75 year old, >75 year old) and included number of patients, site of cancer and site of metastasis. Patient characteristics and survival were compared with Mann-Whitney U, Pearson’s Chi-square, and the Kaplan-Meier method. Results: 167, 059 patients were included in the analysis. In the academic setting, group A (age 50-75) contained 36, 298 patients and group B (>75) contained 13,253 patients. In the community setting, group A involved 77, 657 patients and group B, 39,851 patients. In the academic setting, group A identified 57.7% of cases involving the colon vs 42.3% involving the rectum. In group B, 71.4% cases involved the colon vs 28.6% involving the rectum. In the community setting, group A identified 64.4% of cases involving the colon compared to 35.6% involving the rectum. For group B, 76.2% of cases diagnosed were in the colon vs. 23.8% of cases involving the rectum. Overall, indicating a statistically significant increase seen in colon involvement in the older age group (<0.001). In community and academic practice, there is a statistically significant increase in the cases involving metastasis for group A, compared to group B (p<0.001) This is seen for specific sites as well, including bone, liver and lung, (p< 0.001) but not brain involvement in academic practice. Conclusions: In this study, we found a statistically greater number of cases of involving metastasis in patients aged 50-75 compared to patients aged 75 and older in both academic and community practices. In both the academic and community setting, older patients demonstrated statistically greater involvement of the colon compared to patients aged 50-75. Overall, there were more cases of colon and rectal cancer for both age groups seen in the community setting compared to the academic setting.
Type of 5-fluorouracil and risk of cardiovascular events in early-stage colon cancer.
Authors: Huang Wen Kuan , See Lai-Chu 
Published: June 2021

e15596 Background: Older patients with colorectal cancer are at increased risk of developing cardiovascular (CV) disease. 5-FU-based chemotherapy was found to increase CV morbidity; however, whether CV risks differ among different fluorouracil types, including infusional 5-FU, capecitabine, and tegafur-uracil (UFT), remains unclear. We aimed to assess the association between CV morbidities, including myocardial infarction and heart failure, and different 5-FU types in patients with colorectal cancer. Methods: We evaluated patients from Taiwan Cancer Registry linked with national health insurance research database with stage I to III colorectal cancer between January 1, 2004, and December 31, 2014. A multivariate Cox proportional model with age as the time scale was conducted for comparison. UFT alone was set as the control group. Results: In the cohort of 29176 patients (median [interquartile range] age, 65 [43-79] years), 2241 (7.6%) received UFT, 25181 (86.3%) received infusional 5-FU or capecitabine, 1754 (6%) received mixed. Overall, 290 patients were diagnosed with myocardial infarction (1.78 per 1000 person-years) during a median (interquartile range) follow-up of 5.5 years. Compared with those received UFT, those using infusional 5-FU or capecitabine showed no increased risk of myocardial infarction (weighted hazard ratio [HR], 0.84; 95% CI, 0.57-1.24). There were 376 patients diagnosed with heart failure, corresponding to 2.3 per 1000 person-years. The risks of heart failure between the UFT group and infusional 5-FU/capecitabine were similar (weighted HR, 0.9; 95% CI, 0.62-1.31). Conclusions: In this study, we did not observe any increased CV risk using infusional 5-FU or capecitabine compared with UFT alone use.
Clinical features, treatments and survival of HER2 positive gastric cancer with elevated alpha-fetoprotein: An analysis of 16 cases.
Authors: Ge Shaohua , Ba Yi , Deng Ting , Yang Yuchong , Ning Tao , Li Hongli , Bai Ming , Zhang Le , Duan Jingjing , Liu Rui , Wang Xia , Ji Zhi 
Published: June 2021

e16000 Background: Gastric cancer with elevated alpha-fetoprotein (AFP) is a special type of gastric cancer with elevated serum AFP. It is often misdiagnosed as primary hepatic cancer due to abnormal AFP and liver metastasis. The AFP level is related to the prognosis of these patients in whom there is prone to high HER2 positive rate. Therefore, anti-HER2 treatment is optional, as well as the emerging immunotherapy with immune checkpoint inhibitors. Methods: Gastric cancer patients with HER2 and serum AFP examination were collected in our hospital from May 2017 till now. Serum AFP level over 7 ng/ml was defined as elevated AFP. The clinical characteristics, treatments and survival of the patients with HER2 positive and elevated AFP were picked and analyzed. Results: Among 135 gastric cancer patients with elevated AFP, 16 (11.9%) were HER-2 positive (12 with HER2 3+, 3 with HER2 2+/FISH+ and 1 with HER2 gene amplification in NGS). The mean serum AFP is 201.4± 476.7ng/ml (range: 7.74 -1335). There were 9 males and 7 females. The mean age was 55 years (range: 38-90). The tumors were located in stomach cardia and fundus in 5 cases, body in 5 cases, antrum in 4 cases, body and antrum in 1 case and whole stomach in 1 case. There were 2 patients in stage III and 14 patients in stage IV with metastasis to lymph node metastasis in 15, liver in 9, abdominal cavity in 3 and peritoneum in 3. As for the treatments, three patients underwent surgery, one of whom with exploratory laparotomy (no antitumor treatment after surgery, died from infection). In 13 advanced patients, 12 patients received systemic antitumor therapies (8 with chemotherapy+Trastuzumab+ immunotherapy, 2 with chemotherapy+Trastuzumab, 1 with chemotherapy+ immunotherapy and 1 with chemotherapy). The chemotherapy regimens were XELOX in 5 cases, SOX in 4 cases and FLOT in 2 cases. The response rate was 50% (6 in 12 patients) and the disease control rate was 100%. The median PFS was 7.5 months in first line therapy with six patients without progression disease yet. The longest PFS with PR lasted for 16.5 months with chemotherapy, trastuzumab and immune checkpoint inhibitor. Conclusions: Gastric cancer with HER2 positive and elevated serum AFP is a disease with special clinical characteristics. Patients with advanced diseases can be treated with chemotherapy, trastuzumab +/- immune checkpoint inhibitors. This combination is expected to become a new regimen to improve survival of such special patients.
Pyrotinib combined with SHR6390 in the treatment of refractory advanced HER2 positive gastric cancer or solid tumors: Safety and efficacy results from a phase Id trial.
Authors: Liu Dan , Xu Yingying , Gong Jifang , Yang Fen , Shen Lin , Li Huajun 
Published: June 2021

e16009 Background: Pyrotinib (an irreversible pan-ErbB inhibitor) combined with SHR6390 (a novel oral small molecule CDK4/6 inhibitor) had shown anti-tumor activity in pyrotinib-resistant PDX models. A phase Id trial was conducted to evaluate the safety and efficacy of pyrotinib combined with SHR6390 in the treatment of refractory advanced HER2 positive gastric cancer or solid tumors (NCT03480256). Methods: A standard “3+3” design was conducted in this trial. Patients (Pts) received pyrotinib (qd, d1-28; q4w) combined SHR6390(qd, d1-21; q4w) at dose of 400/100mg (cohort A), 320/100mg (cohort E) and 400/75mg (cohort F) until disease progression or intolerable toxicity. The primary endpoint was safety and maximum tolerated dose. Results: From Sep. 2019 to Dec. 2020, 19 pts (14 gastric cancer, 3 colorectal cancer, 2 other solid tumors) were enrolled (A: n = 6; E: n = 6; F: n = 7). 15 pts received and progressed on Herceptin before enrollment. In cohort A, one DLT was observed (Grade 4 neutropenia), and another 3 pts suffered G3 neutropenia, anemia or thrombocytopenia. Considered of safety, the dose levels were decreased and designed as cohort E and F. In cohort E, one DLT was observed (G4 neutropenia). No DLT was observed in cohort F. The most common hematologic toxicities were neutropenia (95%), anemia (74%) and thrombocytopenia (74%). The most common non-hematologic toxicities were diarrhea (53%), mucositis (26%) and nausea (21%). The most common G3/4 AEs were leukopenia (37%) and anemia (16%). No G3/4 non-hematologic toxicity was observed. 18 pts were included in efficacy analysis. The overall response rate was 38.9%, with 7 PR (A: n = 3; E: n = 2; F: n = 2) and 7 SD. The median PFS was 3.83 months, with 2 pts received treatment over 12 months (A: n = 1; F: n = 1). Conclusions: Pyrotinib combined with SHR6390 had shown acceptable safety profile and encouraging efficacy in refractory advanced HER2 positive solid tumors. Further study would be carried out at the dose in cohort A. Clinical trial information: NCT03480256.
Efficacy and safety of toripalimab combination with SOX regimen as a first-line treatment in patients with unresectable locally advanced or recurrent/metastatic gastric/gastroesophageal junction cancer: Preliminary data from a single-armed, exploratory study.
Authors: Lin Xiaolin , Xia Qing , Han Ting , Zhuo Meng , Yang Haiyan , Qiu Xiaoxia , Wang Liwei , Xiao Xiuying 
Published: June 2021

e16015 Background: Gastric cancer (GC) is one of the most common malignancies of the digestive system with a poor prognosis and limited treatment option. Currently immunotherapy is approved for the third-line treatment of GC, but there are limited data on first-line treatment. Therefore, this study will further explore the efficacy and safety of the domestic PD-1 antibody toripalimab combined with S-1 plus oxaliplatin (SOX) regimen as the first-line treatment of unresectable locally advanced or recurrent/metastatic gastric/gastroesophageal junction cancer. Methods: A prospective, single-armed, exploratory, investigated initiated trial explores the efficacy and safety of toripalimab combined with SOX regimen as first-line treatment of unresectable locally advanced or recurrent/metastatic gastric/gastroesophageal junction cancer. The primary objectives are objective response rate (ORR). Secondary objectives include disease control rate (DCR), DOR, PFS, and OS. The dosage regimen is: Toripalimab, 240mg D1; oxaliplatin, 130mg/m2, D1 ; S-1, 40mg/m2, bid oral D1-14 days, every 21 days as a cycle and plan 6 cycles of treatment. Tumor responses were assessed radiologically every two cycles. Major eligibility requirements include: unresectable advanced, recurrent or metastatic gastric/gastroesophageal junction cancer with diagnoses confirmed histologically or cytologically, age 18 and 80 years, first-line treatment, at least one measurable lesion according to RECIST 1.1, ECOG 0-1, adequate organ function and HER-2 negative. Results: So far, 17 of planned 20 patients have been enrolled. 14 patients completed 2 cycles of treatment, the ORR rate was 57% (8/14) and the disease control rate (DCR) was 93% (13/14). 10 patients completed 4 cycles of treatment, the ORR rate was 60% (6/10) and the disease control rate (DCR) was 90% (9/10). 7 patients completed 6 cycles of treatment, the ORR rate was 43% (3/7) and the disease control rate (DCR) was 57% (4/7). Common adverse reactions during treatment in 17 patients included rash 17.6% (3/17), diarrhea 41.2% (7/17), hypothyroidism 11.8% (2/17), elevated amylase 35.3% (6/17), decreased platelets 41.2% (7/17), mostly grade I-II. Conclusions: Toripalimab combination with SOX regimen as a first-line treatment demonstrated promising anti-tumor activity in unresectable locally advanced or recurrent/metastatic gastric/gastroesophageal junction cancer patients with a good ORR and controllable safety. Clinical trial information: NCT04202484.
Real-world clinical effectiveness and safety of camrelizumab in esophageal squamous cell carcinoma.
Authors: Yao Qiwei , Fu Zhichao , Chen Qisong , Huang Jianli , Wu Jintong , Ke Chunlin , Ma Liangyun , Li Shouguo , He Rongqi , Lin Yuyi , Li Jiancheng 
Published: June 2021

e16023 Background: Camrelizumab, a programmed death 1 (PD-1) inhibitor, has recently demonstrated efficacy for esophageal squamous cell carcinoma (ESCC) patients in a phase III trial. We report real-world clinical outcomes of camrelizumab therapy for ESCC patients in a multicenter prospective cohort. Methods: Eligible patientswereadvanced esophageal squamous cell carcinoma with stage II-IV confirmed by pathology (including histology or cytology). All patients had received at most one systematic treatment and ECOG performance status of 0 or 1. Camrelizumab monotherapy(200mg) or combined with chemo-radiotherapy, chemotherapy, chemotherapy and antiangiogenic therapy as a first or second line of therapy were included. Progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and overall survival (OS) and safety data were evaluated. This abstract summarizes the findings of an exploratory interim analysis (cut-off Dec 2020). Results: From Oct 2019-Dec 2020, 63 patients were enrolled (19 centers in China; mean age 62.26 years; 97% ECOG PS 1; 54% first line therapy). Patients received camrelizumab monotherapy (8; 13%), camrelizumab/chemo-radiotherapy combination therapy (22, 35%), camrelizumab/chemotherapy combination therapy (26, 41%), camrelizumab/chemotherapy/antiangiogenic therapy combination therapy (7, 11%). One patient achieved a complete response and 27 patients achieved a partial response, leading to an ORR of 41.26%. The DCR was 95.24%. The median progression-free survival (PFS) was 6.33 months (95% confidence interval [CI] 4.73-NA). Among patients with adequate samples test for LBH level and (lung immune prognostic index) LIPI score, 15.7% (8/51) patients had a high LBH level;63% (29/46), 32.6% (15/46) and 4.3% (2/46) patients had a good, middle and poor LIPI score, respectively. A significantly longer PFS was observed in patients with a normal LBH level (NA vs. 6.33 months, P = 0.049), and also in patients treated with first-line therapy (6.33 months vs. NA, P = 0.0338). Among adverse events, 4 patients (6.35%) reported grade 3-4 AEs, including pneumonia (n=2 [3.17%]), and bone marrow suppression (n=2 [3.17%]). 10 of 63 patients (15.87%) experienced any grade pneumonia, and 21 of 63 patients (33.33%) experienced grade 1-2 RCCEP. Conclusions: This real-world population showed that camrelizumab as the first- or second-line therapy was an effective and safe treatment for patients with ESCC. Clinical trial information: CHICTR2000039499.
Lymph node metastases of gastric cancer and blood cell circuit.
Authors: Kshivets Oleg 
Published: June 2021

e16024 Background: Significance of blood cell circuit in terms of detection of gastric cancer (GC) patients (GCP) with lymph node metastases was investigated. Methods: We analyzed data of 793 consecutive GCP (age = 57±9.4 years; tumor size = 5.4±3.1 cm) radically operated (R0) and monitored in 1975-2021 (m = 555, f = 238; distal gastrectomies = 460, proximal gastrectomies = 163, total gastrectomies = 170, combined gastrectomies with resection of pancreas, liver, diaphragm, colon transversum, esophagus, duodenum, splenectomy, small intestine, kidney, adrenal gland = 244; D2-lymphadenectomy = 513, D3-4 = 280; T1 = 235, T2 = 220, T3 = 182, T4 = 156; N0 = 433, N1 = 109, N2 = 251; G1 = 222, G2 = 162, G3 = 409; early GC = 162, invasive = 631; only surgery = 621, adjuvant chemoimmunotherapy-AT = 172 (5-FU+thymalin/taktivin). Variables selected for study were input levels of blood cell circuit, sex, age, TNMG. Differences between groups were evaluated using discriminant analysis, clustering, nonlinear estimation, structural equation modeling, Monte Carlo, bootstrap simulation and neural networks computing. Results: It was revealed that separation of GCP with lymph node metastases (n = 360) from GCP without metastases (n = 433) significantly depended on: eosinophils (%, abs, total), thrombocytes (abs, total), ESS, Hb, erythrocytes (abs), residual nitrogen, protein, cell ratio factors (CRF) (ratio between cancer cells- CC and blood cells subpopulations), T, G, tumor size, histology, tumor growth, blood group, procedures type (P = 0.043-0.000). Neural networks computing, genetic algorithm selection and bootstrap simulation revealed relationships of lymph node metastases and CRF: thrombocytes/CC (rank = 1), healthy cells/CC (2), erythrocytes/CC (3), monocytes/CC (4), segmented neutrophils/CC (5), lymphocytes/CC (6), leucocytes/CC (7), eosinophils/CC (8), stick neutrophils/CC (9). Correct classification N0—N12 was 99.9% by neural networks computing (area under ROC curve = 1.0; error = 0.0). Conclusions: Lymph node metastases of gastric cancer significantly depended on blood cell circuit.