bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant versus adjuvant chemotherapy for resectable metastatic colon cancer in non-academic and academic programs.
Authors: Hao Zhonglin , Parasramka Saurabh , Chen Quan , Jacob Aasems , Huang Bin 
Published: June 2022

e15607 Background: Approximately 21% of colon cancer patients have synchronous metastatic disease at presentation. Liver is by far the most common site of metastasis. For resectable and borderline resectable metastatic lesions after conversion to surgical resection, five-year survival ranges between 40-70%. Overall survival advantage of chemotherapy before and after metastasectomy of liver or lung lesion is not clear. We here compare the differential effect of neoadjuvant versus adjuvant chemotherapy on overall survival of patients who received resection of both primary and metastatic lesions in non-academic and academic settings from the National Cancer Database (NCDB). Methods: Adults 20 years or older with primary colon cancer and single organ metastatic disease either in the liver or lung at diagnosis between 2010-2015 were identified. All patients had received surgery to the primary site, resection of the distant site and chemotherapy within 1 year of diagnosis. Patients were categorized into 2 cohorts based on whether they received chemotherapy in the pre-operative/peri-operative setting (neoadjuvant chemotherapy –NAC) or post-operative setting (adjuvant chemotherapy AC). Descriptive analysis, Kaplan-Meier plots, Log-Rank tests, and Cox-regression models for multivariate survival analyses were performed. To assess uncertainty of estimates, a sensitivity analysis was also performed based on the intention to treat principle by including additional surgery only and chemotherapy only cases. Results: A total of 3,038 colon cancer patients with liver or lung metastases were identified between 2010-2015. A larger majority of patients (n = 2387, 78.6%) received AC. The percentage of patients receiving NAC had steadily increased from 2010-2015 from 12.29% to 28.31%. The supermajority of metastases was in the liver. On multivariate analysis, patients who received NAC had an overall survival advantage (HR 0.661; 95% CI 0.534-0.879; P = 0.0001) in the non-academic setting whereas no advantage is seen in the patients treated in the academic settings (HR 0.994; 95% CI 0.831-1.189; P < 0.9484). The median overall survival for patients receiving NAC and AC was 47.24 months and 38.08 months respectively. Clinical factors associated with overall survival advantages in NAC patients treated in non-academic programs included age 20-49 years; low-income (< $38,000/year) status; CEA value of > 30; right sided colon primary; low T status and liver metastasis among others. The survival advantage of NAC over AC is associated with more clean resection margin and fewer regional lymph node involvement after surgery. Conclusions: Metastatic colon cancer with single organ liver or lung lesions benefits from neoadjuvant chemotherapy especially in non-academic settings based on our analysis of the NCDB database. The overall survival advantage in this setting has not been shown before.
Prognosis of patients with resected stage II colon cancer -T4 versus T3 with two or more high-risk factors: A retrospective single-center cohort study.
Authors: Fedyanin Mikhail , Rice Anastasia , Polyanskaya Elizaveta , Gordeev Sergey , Mammadli Zaman , Tjulandin Sergei , Tryakin Alexey 
Published: June 2022

e15608 Background: in 2021 ASCO has updated guidelines on adjuvant therapy for stage II colon cancer with the statement: “Patients with T4 tumors are at higher risk of recurrence and should be offered adjuvant chemotherapy, whereas patients with other high-risk factors, including sampling of fewer than 12 lymph nodes in the surgical specimen, perineural or lymphatic invasion, poorly or undifferentiated tumor grade, intestinal obstruction, tumor perforation, or grade BD3 tumor budding, may be offered ACT”. We performed a single-center retrospective study to assess the prognostic role of postoperative tumor stage T4 and T3 with ≥2 negative prognostic factors in patients with resected stage II colon cancer. Methods: We retrospectively analyzed 1457 pts with stage I-III colon cancer treated in Russian Cancer Research Center n.a. N.N. Blokhin from 2001 to 2015. We included pts with resected stage II colon cancer with following negative prognostic factors: T4; sampling of fewer than 12 lymph nodes in the surgical specimen; perineural or lymphatic invasion; poorly or undifferentiated tumor grade; intestinal obstruction; and tumor perforation. Three cohorts were studied: pts with pT4N0M0 with no other high-risk factors (group A), pts with pT4N0M0 with additional high-risk factors (group B), and pts with pT3N0M0 with ≥2 high-risk factors (group C). The primary study endpoint was 3-year disease-free survival (DFS). The secondary endpoint was 5-year overall survival (OS). Statistical analysis was done with SPSS v.20. Results: 164 pts met the inclusion criteria with 17 (10%) pts in group A, 90 (55%) pts in group B, and 57 (35%) pts in group C. Adjuvant chemotherapy was performed in 8 (47%), 25 (28%), and 9 (16%) pts, respectively (p = 0.035). At a median follow-up of 62 months (range, 2-135 months), the 3-year DFS was 82%, 68%, and 78% for groups A, B, and C, respectively (HR, 1.55; 95% CI, 0.99-2.4; p = 0.053). No difference in 3-year DFS was found between group A and C (HR, 1.0; 95% CI, 0.34-3.2; p = 0.9). The 5-year OS was 75%, 65%, and 78% for groups A, B, and C, respectively (HR, 1.38; 95% CI, 0.84-2.3; p = 0.2). Conclusions: Patients with pT4 with additional high-risk features had worse overall survival compared to other subgroups with resected stage II colon cancer. There was no difference in survival rates between patients with pT4 with no additional negative prognostic factors and pT3 with ≥2 negative prognostic factors. Therefore, we propose that patients with pT4 as well as with pT3 with ≥2 negative prognostic factors are at a higher risk of recurrence and should be offered adjuvant chemotherapy.
Thromboprophylaxis in surgically treated colorectal cancer patients with tinzaparin: Intermediate results from the Onco-CAST trial.
Authors: Papadopoulos V.N. , Timotheadou E.I. , Aggelopoulos St. , Arkadopoulos N. , Manganas D. , Papavasileiou Ch. , Papaziogas V. , Tzovaras G. , Alexandrou D. , Baloyiannis I. , Flamourakis M. , Galanis I. , Perivoliotis K. , Pramateftakis Manousos-Georgios , Bachlitzanakis Em. , Koffas S. , Menni A. , Papadoliopoulou M. , Tzitzis P. , Michalopoulos Antonios ,   Hellenic Society of Coloproctology
Published: June 2022

e15611 Background: The incidence of Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) after colorectal surgery is approximately 29% and 1.6% respectively. The incidence of asymptomatic postoperative DVT in colorectal cancer (CRC) patients has been reported as high as 20%, even under thromboprophylaxis. Thus, thromboprophylaxis after surgical treatment for CRC is crucial. Latest guidelines from International Initiative on Thrombosis and Cancer (ITAC 2019) recommend use of highest prophylactic dose of Low Molecular Weight Heparin (LMWH). Methods: Onco-CAST is a prospective, phase IV, observational, non-interventional cohort study evaluating a) current management approach for CRC surgical prophylaxis and b) efficacy and safety of tinzaparin at 8.000 Anti-Xa IU, once daily (OD), for at least one month post hospital discharge. Patients enrolled after signing informed consent. Onco-CAST was conducted by the Hellenic Society of Coloproctology. Results: Results from 175 CRC patients from 9 Onco Surgical Clinics are reported. Participation completed 79% of patients at report time: 66% males, 67±12 years, BMI: 27.4±5.5. Histology: adenocarcinomas NOS 81%, mucinous adenocarcinomas 9%, small cell neuroendocrine carcinomas 2%, and others. High grade differentiation indicated: 26% and 5% metastatic. 32% treated with right hemicolectomy, 20% with low anterior resection, 12% with sigmoid colectomy, 9% with abdominal-perineal resection, 9% with left hemicolectomy and other methods. 67% treated open and 33% laparoscopic while the median number of lymph nodes dissected for left and right hemicolectomy was 32.5 (Q1-Q3:26-38) and 24 (Q1-Q3: 14.5-32), p = 0.0253. Factors related to thrombosis risk are presented in table, notably, 95% of patients accumulated ≥3 risk factors. Median thromboprophylaxis duration with tinzaparin 8.000 Anti-Xa IU, OD, was: 37 days (1st-3rd quartile: 33-45 days). Three thrombotic events occurred (efficacy 98.3%, 95% CI: 95.1-99.4%), one DVT+PE, one DVT and one due to Central Venous Catheter (CVC). Eight patients experienced bleeding events (4.6%, 95%CI: 2.3-8.8%), 3 minor, 3 major and 2 CNMB, 2 had a possible relation to thromboprophylaxis (1.1%, 95%CI: 0.3-4.1%). Conclusions: Thromboprophylaxis in Surgically Treated Colorectal Cancer Patients with Tinzaparin intermediate dose seems safe and efficient approach.[Table: see text]
Patient-derived xenografts of colorectal cancer for testing new pharmacological substances.
Authors: Egorov Georgiy Yu. , Goncharova Anna S. , Khodakova D. V. , Kurbanova L. Z. , Mindar Maria V. , Zaikina Ekaterina V. , Komarova Ekaterina Fedorovna , Kolesnikov Evgeniy N. , Maksimov Aleksey Yu. , Katsieva Tanzila B. , Myagkov Roman E. , Averkin Mikhail A. , Snezhko Aleksandr V. , Gaziev Umar M. , Nikolaeva Nadezhda V. 
Published: June 2022

e15612 Background: The purpose of this study was to create a patient-derived xenograft model of human colorectal cancer and to determine its histological and molecular characteristics, including the status of the KRAS, NRAS, BRAF genes and the presence of microsatellite instability factors. Methods: Biological materials obtained from tumors of 4 patients with colorectal cancer were used to create the first-generation in vivo model. The study was performed on immunodeficient Balb/c Nude mice (20 females aged 5-6 weeks). Subcutaneous xenografts were obtained by the implantation of a 3×3×3 mm donor tumor fragment to recipient animals under the skin of the right thigh, 5 samples from each patient. For the second, third and fourth PDX generations, mice of the same strain were used (n = 3 for each generation). All manipulations were performed in accordance with the rules for using laboratory animals. Genomic DNA was extracted from PDX samples, and mutations in exons 2, 3 and 4 of the KRAS and NRAS genes and BRAF V600 mutations were identified by direct sequencing. Microsatellite instability was determined by fragment analysis for five loci Bat-25, Bat-26, NR21, NR24, NR27. Results: Stable transplantable xenografts of colorectal cancer were obtained from two out of four patients. The average waiting time between implantation and growth of the first-generation xenograft was 28 days. The model was confirmed to reproduce the histotype, differentiation and mutational status of the KRAS, NRAS, BRAF genes and microsatellite instability similar to those of donor tumors. Conclusions: The results confirm the possibility of the model use for testing both new pharmacological substances with a cytotoxic effect and drugs based on monoclonal antibodies.
Oxaliplatin and capecitabine (XELOX) plus toripalimab as perioperative treatment for locally advanced gastric or gastro-esophageal junction adenocarcinoma (Neo-Capture): A single-arm, phase 2 study.
Authors: Jiang Zhichao , Xie Yibin , Wang Bingzhi , Zhu Yongjian , Ke Yan , Zhang Wen , Sun Yongkun , Li Yin , Wang Chengfeng , Zhao Dongbing , Tian Yantao , Zhou Ai-Ping 
Published: June 2022

e16001 Background: PD-1 inhibitor combined with chemotherapy showed remarkable objective response rate in the first line treatment of metastatic gastric cancer. While, the benefit of perioperative PD-1 inhibitor plus chemotherapy in locally advanced gastric or gastro-esophageal junction (G/GEJ) cancer was not clear. Therefore, we aimed to assess the efficacy and safety of perioperative XELOX plus toripalimab in the patients with locally advanced G/GEJ cancer in this study. Methods: This was a prospective single arm phase 2 study. Eligible patients were with histologically confirmed locally advanced G/GEJ (Siewert II/II type) adenocarcinoma (cT3-4 Nany M0 or T1-2 N2-3 M0). Patients received 4 preoperative and 2 postoperative cycles of XELOX plus toripalimab (oxaliplatin 130mg/m2 D1, capecitabine 1000mg/m2 bid D1-14, toripalimab 240mg D1, Q3W) followed by subsequent 2 cycles of toripalimab monotherapy. Patients underwent D2 gastrectomy after preoperative treatment. The primary endpoint was major pathological response (MPR) according to Becker TRG criteria. Secondary endpoints included safety, R0 resection rate, pathological complete response (pCR), 3-year disease free survival (DFS) and 3-year overall survival (OS). Results: From Jul, 2019, to Dec, 2021, 35 pts were recruited. The median age was 61 (34-72) years old. 80% of the pts were men. Acutally, all the pts had cT4 (cT4a [48.6%] & cT4b [51.4%]) and 88.6% had cN+ by CT, MRI and ultrasound gastroscopy. 2 pts suffered disease progression during neoadjuvant treatment. 4 pts have not yet completed preoperative therapy. 29 pts had received gastrectomy and 2 pts were pathologically diagnosed with large cell neuroendocrine carcinoma. Therefore, 27 adenocarcinoma pts were included in this analysis. 3 (11.1%) pts achieved pCR (TRG1a) and 4 (14.8%) pts achieved MPR (TRG1a/b). R0 resection was achieved in 96.3% (26/27) of the pts. No patient had pT4b. The most common (≥10%) grade 1-2 treatment related adverse events (TRAEs) included leucopenia (45.7%), neutropenia (42.9%), thrombocytopenia (20%), nausea (34.1%), vomiting (14.3%), anorexia (14.3%), ALT increased (40%) and AST increased (34.3%). Only 4 (11.4%) pts experienced grade 3 neutropenia. No other ≥ grade 3 TRAEs occurred. Most of the potential immune-related adverse events were grade 1-2 including hypothyroidism (8.6%), adrenal insufficiency (2.9%) and hyperglycemia (11.4%). Only one (2.9%) patient had grade 3 hyperglycemia. No serious perioperative complication and death occurred. Conclusions: Perioperative XELOX plus toripalimab preliminarily showed a favorable R0 resection rate and acceptable MPR in cT4a/T4b locally advanced G/GEJ cancer patients with a manageable safety profile. Clinical trial information: NCT04119622.
Neoadjuvant sintilimab combined with chemotherapy in patients with resectable esophageal squamous cell carcinoma (ESCC): Preliminary results from a phase II study.
Authors: Guo Jincheng , Qiao Chengrui , Lu Jiabin , Yang Shiqing , Zhang Boyi 
Published: June 2022

e16008 Background: Although preoperative chemoradiotherapy is the standard of care for patients with resectable locally advanced esophageal cancer, prognosis still remains poor. Combining PD-1 blockade to chemotherapy has demonstrated significant clinical benefits in first line treatment of metastatic ESCC. Sintilimab, a fully human IgG4 monoclonal antibody that binds to programmed cell death receptor-1 (PD-1), has shown remarkable clinical efficacy in metastatic ESCC. We aimed to assess the activity and safety profile of the combination of sintilimab with paclitaxel and cisplatin for neoadjuvant treatment of ESCC. Methods: In this ongoing, single-arm, phase II study, we recruited patients from the First Affiliated Hospital of Henan University of Technology in China with histopathologically diagnosed resectable ESCC who had clinical cT2-4/N1-3M0 (stage II-IVA). Patients were given 2 cycles of chemotherapy (nab-paclitaxel 260 mg/m2, d1 and cisplatin 75 mg/m2, d1-3) in combination with 2 cycles of sintilimab (200mg, iv, d1, q3w), followed by esophagectomy. The primary endpoint was pathological complete response (pCR). The secondary endpoints included major pathological remission (MPR) and objective response rate (ORR). Results: Between Nov 2020 and Dec 2021, 15 patients were enrolled and commenced treatment. A total of 11 patients (75%) completed neoadjuvant and radical resection, 4 patients refused surgery. Six patients (54.5%) achieved major pathologic response (MPR), including five (45.5%) with a pathologic complete response (pCR) in primary tumor. According to RECIST v1.1, 1 of 8 patients (12.5%) achieved partial response (CR), 4 of 8 patients (50%) achieved partial response, and 3 of 8 patients (37.5%) achieved stable disease (SD). The objective response rate (ORR) and disease control rate (DCR) for 8 patients were 62.5% and 100%, respectively. The most frequent treatment-related adverse events (TRAE) included leukopenia (60%), nausea (40%) and diarrhea (20%). The grade 3 or 4 TRAE were leukopenia (26.7%), neutropenia (20%) and pneumonia (6.7%). There was no surgical delays or unexpected surgical complications related to drug toxicity. Conclusions: Neoadjuvant combination of sintilimab and chemotherapy is a safe and efficacious treatment option for patients with resectable ESCC, and 45.5% pCR rate is encouraging. Our clinical study is still enrolling, and the survival effects are under follow up. Clinical trial information: ChiCTR2000040345.
Sintilimab combined with chemotherapy in conversion therapy of advanced gastric cancer: A retrospective study.
Authors: Fang Jingquan , Huang Xingmao , Cao Yang , Ye Zeyao , Chai Tengjiao , Du Yian , Pengfei Yu 
Published: June 2022

e16012 Background: Gastric cancer is the fifth most common cancer in the world and the third leading cause of cancer death. At present, traditional chemotherapy is still the main treatment method of advanced gastric cancer, but the efficacy is limited. Immunotherapy has been identified as a treatment for chemotherapy-refractory gastric cancer, and sintilimab is a fully human IgG4 monoclonal antibody that binds to programmed cell death receptor-1 (PD-1). This study aims to investigate the efficacy of sintilimab combined with chemotherapy in patients with inoperable metastatic gastric cancer and analyze the prognostic factors of these patients. Methods: Patients with advanced gastric cancer which were initially treated unresectable and with distant metastasis in Zhejiang Cancer Hospital from August 2018 to December 2021 were retrospectively analyzed in this research. Patients received sintilimab combined with chemotherapy (PS regimen) ：sintilimab 200mg, day 1, paclitaxel was administered intravenously (150 mg/m2 ) on day 1, and S-1 was administered orally (80 mg/m2/day) on days 1–14 of a 3-week cycle. The primary endpoints were treatment efficiency; and the secondary endpoint was safety and overall survival (OS) time. Results: A total of 66 patients were enrolled, including 43 males and 23 females, with an average age of 62.2 years (29-77 years). All of these patients had one or more distant metastases (liver 28 cases, peritoneum 20 cases, retroperitoneal lymph node 21 cases and ovary 5 cases). 33 patients (50%) underwent surgery, including conversion surgery (26 cases), palliative surgery (7 cases). The mean OS of patients with conversion surgery was 19.2 months (95%CI 16.5̃21.9 months), and the 2-year survival rate was 50.0%. The mean OS of non-conversion surgery was 16.9 months (95%CI 12.9̃20.1 months), and the 2-year survival rate was 29.1% (P=0.028). 24 (92.3%) cases had R0 resection. Multivariate analysis showed that postoperative CA125 level was an independent risk factor for prognosis of these gastric cancer patients. Conclusions: Sintilimab combined with chemotherapy is safe and effective, and combined with conversion surgery can improve the prognosis of patients with partially unresectable advanced gastric cancer.
Anlotinib combined with nab-paclitaxel and cisplatin as neoadjuvant treatment for esophageal squamous cell carcinoma (ESCC): A single-arm, open-label phase II clinical trial.
Authors: Zhang Yan-Feng , Hao An-Lin , Hong Yong-Gui , Li Xiao-Ming , Liang Wei-Min , Zheng Zhi-Xin , Yang Guang-Yi , Guo Xiao-Feng , Wen Yan-Yan , Cao Heng , Le Cheng , Song Hua-Jie , Su Wen-Zhong 
Published: June 2022

e16015 Background: Neoadjuvant therapy could significantly improve survival for patients with locally advanced esophageal cancer. However, postoperative complications and recurrence are still urgent problems to be solved. Anlotinib was an effective second-line monotherapy for ESCC in China and the combination therapy might be a promising strategy. Nab-paclitaxel plus cisplatin as first-line therapy exhibited moderate efficacy in ESCC patients. This study was to investigate the efficacy and safety of nab-paclitaxel and cisplatin combined with anlotinib as neoadjuvant treatment for ESCC. Methods: ESCC patients with preoperative clinical stage II-III and all patients who can receive radical surgery were recruited in this study. Eligible patients received anlotinib (12mg, po, d1̃14, q3w) combined with nab-paclitaxel (175mg/m2, iv, q3w) and cisplatin (20mg/m2, iv, d1̃3, q3w) for 2 cycles during neoadjuvant therapy. 4 weeks after the end of neoadjuvant therapy, the patients underwent radical surgery after exclusion of contraindications to surgery. Tumor response was assessed by investigator according to RECIST version 1.1 using CT scans at baseline and within 2 weeks before surgery. The calculated sample size was 62. The primary endpoint was ORR, secondary endpoints were R0 resection rate, DFS, OS, DCR and safety. Results: From Apr 2021 to Dec 2021, a total of 26 eligible patients were enrolled. Among them, 17 patients underwent surgery after completing 2 cycles of neoadjuvant therapy, 3 patients chose other treatment options, and 6 patients are still receiving neoadjuvant therapy. patients who had received surgery (n = 17) were included in this analysis. In best overall response assessment, there were 4 CR (23.5%), 11 PR (64.7%) and 2 SD (11.8%). Consequently, ORR was 88.2% (95%CI: 63.6̃98.5%) and DCR was 100.0% (95%CI: 80.5̃100.0%). At the data cut-off date, 17 patients (100.0%) had underwent R0 resection. Among them, 4 patients (23.5%) were confirmed to be pCR. And the median DFS was not yet available. The safety profile suggested that the most common treatment-emergent adverse events with the incidence > 10% were gastrointestinal reactions (65.4%), hypokalemia (19.2%), nausea (15.4%), liver damage (15.4%), myelosuppression (11.5%) and vomit (11.5%). No grade ≥3 adverse events were noted. Conclusions: Preliminary results suggested that anlotinib combined with nab-paclitaxel and cisplatin in neoadjuvant treatment of ESCC exhibited encouraging efficacy and manageable adverse events. The conclusion should be validated in more patients included subsequently.