bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regorafenib in refractory metastatic colorectal cancer: A multi-center retrospective study.
Authors: Xu Donghao , Liu Yu , Tang Wentao , Xu Lingsha , Liu Tianyu , LI Jisheng , Zhao Jiemin , Ye Le-chi , Xu Jianmin , Chang Wenju 
Published: June 2022

e15580 Background: Regorafenib improves progression-free survival (PFS) and overall survival (OS) in patients with refractory metastatic colorectal cancer (mCRC). Here, we report the treatment patterns of regorafenib in the third- or late-line setting for mCRC in four centers in China. Methods: Patients with refractory mCRC in four centers in China administered regorafenib from February 1, 2018 to June 31, 2021 were enrolled. Patients were grouped into 3 cohorts, including the monotherapy (regorafenib alone), chemo (regorafenib plus chemotherapy) and immune (regorafenib plus anti-PD1 (programmed cell death 1) antibodies) groups. Demographic, clinical, survival and safety data were retrospectively analyzed. Results: A total of 177 patients were included in this study. Of them, 116 (65.5%) were treated with regorafenib alone, while 28 (15.9%) and 33 (18.6%) were administered regorafenib plus chemotherapy and anti-PD1 antibodies, respectively. The median followedup time was 9.2 months. The disease control rate (DCR) was 40.7%. The median PFS (mPFS) was 2.43 months and the median OS (mOS) was 12.2 months. The immune group had longer median PFS (3.5 m vs. 2.2 m, p = 0.043) compared with the monotherapy group. Patients administered regorafenib plus chemotherapy had longer median OS (15.9 m vs. 8.4 m, p = 0.032) compared with the monotherapy group. Patients who began regorafenib treatment at 120 mg had longer median PFS and OS compared with those who began at 80 mg (PFS: 3.7 m vs. 2.0 m; p < 0.001; OS: 13.4 m vs. 10.2 m; p = 0.005). Patients with a final dose of 120 mg had longer median PFS and OS compared with the 80 mg or less group (PFS: 5.0 m vs. 2.3 m; p = 0.045; OS: UR (unreach) vs. 10.9 m; p = 0.003). There were 87.0% (154/177) patients experience AEs. Three groups had similar rates of AEs (86.2% vs. 89.3% vs. 87.9%; p = 0.89). Conclusions: Patients administered regorafenib alone or regorafenib in combination with other agents were relieved to some extent, with a disease control rate of 40.7%. Regorafenib plus anti-PD1 antibodies showed better PFS, while regorafenib plus chemotherapy had the most benefit in OS. There was no significant difference among three groups in terms of AEs.
The safety assessment of COVID-19 vaccine injection in patients with colorectal cancer.
Authors: Wei FangFang , Huang Jun , Huang Lihua , Pei Fengyun , Huang Meijin 
Published: June 2022

e15585 Background: With the unprecedented morbidity and mortality associated with the COVID-19 pandemic, vaccine against COVID-19 has been more and more popularized in general population. However, the safety of COVID-19 vaccine injection in patientswith malignant tumors, such as colorectal cancer (CRC), remains unclear. Methods: During January 2021 and January 2022, 148 CRC patients treated in the department of colorectal surgery in the Sixth Affiliated Hospital of Sun Yat-sen University were enrolled in this cohort. The clinical data and COVID-19 vaccine injection outcome data was collected and analyzed retrospectively. Patients who received at least one dose of COVID-19 vaccine injection were set as an observation group and those who did not get any vaccine injection were set as a control group. The median follow-up time was 8.0 months, vaccine-related adverse events (VRAEs) were collected by questionnaire. The disease progression status of CRC was also compared between the two groups. Results: Eighty-three CRC (male: female 44:39) patients enrolled in this study have got at least one dose of COVID-19 vaccine injection, with a median follow-up time of 8.0 (2.0–13.0) months and no VRAEs reported. Among the vaccinated patients, 51 patients were injected with inactivated vaccine (Sinovac Life Sciences Co., Ltd.), 10 patients were vaccinated with inactivated vaccine (Beijing Institute of Biological Products Co., Ltd.), others were injected another inactivated vaccine (Chengdu Institute of Biological Products Co., Ltd.). The reasons of the 65 patients (male: female 36:29) who did not injected COVID-19 vaccine including: 53 patients had a concern that vaccination will affect the progress of CRC, 8 patients had a concern of old age to get vaccinated and 4 patients did not give any reason. As for disease progression, 14 patients in the observation group had tumor recurrence or progression, while 8 patients in control group reported tumor recurrence or progression, with a median follow-up time of 8.0 (2.0–13.0) months. There was no significant difference in short-term disease progression between the observation group and the control group (P = 0.439). Conclusions: Under the background of COVID-19 pandemic and vaccination of general population, it might be necessary for the patients with malignant disease, such as CRC, to get vaccinated due to whose weaken immune system. COVID-19 vaccine injection is safe for CRC patients and COVID-19 vaccination would not affect the patients’ prognosis.
Clinician utilization of a plasma-only, multiomic minimal residual disease (MRD) assay in 2,000 consecutive patients with colorectal cancer (CRC).
Authors: Pedersen Katrina Sophia , Bucheit Leslie A. , Tan Benjamin R. , Hu Zishuo Ian , Shusterman Michael , Weipert Caroline , Banks Kimberly 
Published: June 2022

e15586 Background: Circulating tumor DNA (ctDNA) for detection of MRD in resected CRC is a prognostic factor for recurrence. However, current utilization of available commercial tests has not been investigated. We report real world clinician use of a validated, plasma-only, multiomic MRD assay (Guardant Reveal) in a large unselected CRC cohort. Methods: Results from Guardant Reveal MRD testing ordered for clinical care in the US were retrospectively queried for the first 2,000 consecutive CRC cases. Pts could be enrolled in a post-operative program to inform adjuvant treatment (PostOP, up to 3 tests within 3-16 weeks post-resection) or a surveillance program (SP) for recurrent tests post-treatment. Pts could have tests across both programs and/or one-time tests. All subsequent tests for the first 2,000 patients were included for analysis (data cut-off: 1/15/2022). Recurrent programs were analyzed for stage (stg) II/III only. Clinical factors were derived from test requisition forms. Results: 2681 tests from 1993 pts were analyzed; 7 pts were excluded due to missing cancer stage. Median age was 64 years (range: 21-65), 55% were male, most (94%) had stg II/III disease (Table). ctDNA was detected in 25% of all pts; detection increased with stage (Table) as expected. Among stg II/III pts, 330 (21%) had only PostOP test/s, 950 (51%) SP only, 54 (3%) had both PostOP and SP; the remainder had one-time test/s outside defined programs. In Stg II/III pts with >1 PostOP test (26%/17% respectively), ctDNA was detected in 102/384 (27%), of whom 72% had it detected on the first test. The median time from surgery to first result was 5 weeks (10 weeks for a second result). 95% of all stg II/III pts had results from PostOP testing before week 12 post-resection. In Stg II/III pts with >1 SP test (47%/54% respectively), ctDNA was detected in 244/1024 (24%), of whom 87% had it detected on a first test. The average time from date of surgery to first surveillance test was 305 days (median: 489, range:51-4618). Conclusions: ctDNA detection rates by a plasma-only multiomic MRD assay in this large CRC clinical cohort are similar to published rates. ctDNA orders by clinicians were most frequent in Stg II/III surveillance settings followed by PostOp, consistent with the population size of eligible patients for PostOp vs. Surveillance use-case. Importantly, nearly all pts tested PostOP had results prior to 12 weeks post-resection, which may inform adjuvant therapy decisions. These findings should be correlated with clinical outcomes to improve the utilization and utility of MRD testing in adjuvant management of CRC. [Table: see text]
High-risk MSI-H stage II colon cancer: Treatment patterns and outcomes.
Authors: Fleming Patrick , Chen Chunxia , Moore Dirk F. , Hochster Howard S. , Jabbour Salma K. , Berim Lyudmyla Derby , Spencer Kristen Renee , Gulhati Pat , Donohue Kristen , Maloney Patel Nell , Boland Patrick M 
Published: June 2022

e15587 Background: For resected stage II MSI-high (MSI-H) colorectal cancer (CRC) without high-risk features (HRF), standard of care recommendation per NCCN guidelines is observation. For tumors with HRF, the prognostic significance and impact of adjuvant therapy remains uncertain. The NCDB was queried to assess outcomes. Methods: Adult patients with stage II MSI-H CRC, surgically resected between 2010 and 2017, were identified in the NCDB. Univariate and multivariate Cox proportional hazards models and Kaplan Meier survival curves were generated to assess impact of HRF, clinical and demographic variables, and chemotherapy use on overall survival (OS). Results: 9634 patients with stage II MSI-H CRC who met criteria were identified. In multivariate analysis T4 tumor status, < 12 lymph nodes (LN) examined, perineural invasion (PNI) and positive margins were associated with worse OS, as were older age and increased comorbidity index (CDCC). Poor differentiation and lymphovascular invasion (LVI) were not associated with OS. No OS difference was observed between T4a vs T4b tumors or based upon tumor sidedness, tumor size, or sex. Excluding poor differentiation (33%) and LVI (17%), HRFs were present in 26% of cases: 21% (n = 2033) had 1 HRF and 5% (n = 505) had > 1 HRF. HRFs were associated with decreased 5-year OS. For 1 HRF OS was 66% (HR 1.48, p < 0.0001) and for > 1 HRF OS was 54% (HR 2.31, p < .0001), compared to 77% with 0 HRFs. HRF presence was associated with increased chemotherapy use: 46% for > 1 HRF, 26% for 1 HRF, and 8% with 0 HRFs. pT4 tumors (T4b > T4a) and younger age were also associated with increased chemotherapy use. By age group, chemotherapy was utilized in 31% of those < 50, 27% of those 51-60, 17% of those 61-70 and 6% of those > 70 years old. In the overall population, chemotherapy administration was associated with improved OS on multivariate analysis compared with no treatment (N = 1344; HR 0.76, p < 0.0001). 69% of patients received multi-agent chemotherapy. However, survival was similar between those receiving single-agent vs multi-agent chemotherapy (HR 1.2, p = 0.2016). In patients < 60 years old, chemotherapy use was associated with decreased OS (HR 1.4, p = 0.0156). Conclusions: In this retrospective, uncontrolled large database survey, HRFs are associated with decreased OS in stage II MSI-H CRC. This data indicates that poor differentiation and LVI do not independently worsen outcomes, but that the presence of multiple HRFs bears relevance. Though chemotherapy was associated with improved OS, the association is reversed in the < 60 year old population; this analysis cannot fully control for extent of disease and PS, among other factors. Chemotherapy should be judiciously administered in Stage II MSI-H CRC with HRFs. Immunotherapy trials are justified.[Table: see text]
Clinicopathological characteristics and prognostic factors of 130 patients with Krukenberg tumors of gastric origin.
Authors: Lin Xiaolin , Han Ting , Zhuo Meng , Liu Tengfei , Liu Zebing , Xiang Dongxi , Li Hong , Xiao Xiuying 
Published: June 2022

e16023 Background: Krukenberg tumors of gastric origin have a poor prognosis. Their clinicopathologic characteristics are rarely reported and they lack optimal clinical management. There is an urgent need to explore new strategies to improve patient survival and quality of life. Methods: The clinicopathological characteristics, treatments and survival data were collected and analyzed from 130 patients with Krukenberg tumors of gastric cancer. Results: The median age of the patients was 41 years. A total of 63.1% of patients had synchronous ovarian metastasis, 70.8% had bilateral ovarian metastasis, 68.5% had peritoneum metastasis, and 98.4% had pathologically poorly differentiated adenocarcinoma. The positive rate of HER-2 was 1.8%. Only one patient showed dMMR. The follow-up rate was 90.8%. The median OS from the diagnosis of ovarian metastasis was 13.0 months. Univariate analysis showed that the significant survival factors included menstrual status, size of the gastric lesion and ovarian metastasis, number of lymph node metastases, interval time to ovarian metastasis, resection of gastric foci, peritoneal metastasis, oophorectomy, chemotherapy after ovarian metastasis, 2-drug regimen chemotherapy, albumin, serum CA-125 level, platelet count, D-dimer, fibrinogen, pretreatment high FAR, PLR and SII. Further multivariable analysis found that albumin, peritoneal metastasis and oophorectomy were independent prognostic factors. Conclusions: Patients of gastric cancer with Krukenberg tumors had some unique clinical characteristics. Active improvement of hypoalbuminemia, treatment of hypercoagulability, management of peritoneal metastasis, timely oophorectomy and chemotherapy can improve the patients’ prognosis. This suggests that we should focus on the nutritional status and coagulation function of patients with Krukenberg tumors in our clinical work.
A phase II single-center single-arm study of PD-1 inhibitor in combination with albumin paclitaxel and apatinib as second-line treatment of metastatic gastric cancer (mGC).
Authors: Gou Miaomiao , Qian Niansong , Wang Zhikuan , Yan Huan , Zhang Yong , Si Haiyan , Dai Guanghai 
Published: June 2022

e16024 Background: Immune checkpoint inhibitors have been approved for first- or third-line treatment of metastatic gastric cancer. However, pembrolizumab alone did not improve overall survival compared to second-line chemotherapy in the KEYNOTE-061 study. We aimed to explore the safety and efficacy of a three-drug regimen by carrying out a clinical study of PD-1 inhibitor combined with albumin paclitaxel and apatinib (VEGFR inhibitor) in the second-line treatment for patients with metastatic gastric cancer(mGC). Methods: This study was a single-center, single-arm phase II clinical study. patients harboring microsatellite stable (MSS) who had previously failed in first-line treatment were enrolled. The enrolled patients were given PD-1 inhibitor (PD-1 inhibitor selected according to the patients’ requirements) in combination with albumin paclitaxel (125 mg/m2 IV, D1, 8 days or 250 mg/m2 IV, D1, 250 mg and apatinib 250 or 500 mg orally for D1-21 days, every 3 weeks as a cycle). The primary endpoints were progression-free survival (PFS) and objective response rate (ORR), while the secondary endpoints were overall survival (OS) and safety (AEs), disease control rate (DCR). Results: From July 11, 2019 to December 1, 2021, a total of 23 patients were enrolled, of whom 10 had negative PD-L1 expression, 1 had PD-L1 > 70% expression, and 4 had positive PD-L1 expression. Preliminary results showed 8 cases had partial response (PR), 10 cases had stable disease (SD), and 5 cases of progression disease (PD). ORR was 34.8% and DCR was 78.3%. The median PFS was 5.04 m, and the median OS was not reached. The main adverse reactions of grade 1 to 2 were bone marrow suppression (42.8%), hand-foot reaction (21.4%), hypertension (21.4%), gastrointestinal bleeding (13.0%), hypothyroidism (8.7%), and liver function damage (8.7%). No grade 3-4 adverse reactions were reported. Conclusions: PD-1 inhibitor combined with albumin paclitaxel and apatinib in the second-line treatment of metastatic gastric cancer showed certain efficacy and safety. At present, this study is ongoing to further confirm the anti-tumor effect and survival benefit of this regimen. Clinical trial information: NCT04182724.
Responses to the MET inhibitor tepotinib in gastric cancers with MET amplification or both high PD-L1 expression and an MET exon 14 skipping mutation.
Authors: Zang Dae Young , Sohn Sung-Hwa , Sul Hee Jung , Kim Bum Jun , Kim Hyeong Su 
Published: June 2022

e16037 Background: Aberrant expression of MET involving MET exon 14 (METex14) alteration and high CNV, which leads to enhanced tumorigenesis. In addition, the PD-L1 (CD274) is often upregulated in cancers. This study characterized expressions of MET (including METex14 skipping mutation), PD-L1 and CD44 in human gastric cancer (GC) cell lines, and further characterized the differential susceptibility of these cell lines to tepotinib. Methods: We assessed the antitumor activity of tepotinib in GC cell lines. CNV analysis using targeted next-generation sequencing (NGS) techniques. The effect of tepotinib on cell viability (IC50), apoptotic cell death, migration, the PD-L1, CD44 and c-MET signaling were evaluated by MTS assay, flow cytometry, wound-healing assay, western blotting, and qRT-PCR. Results: Tepotinib treatment showed dose-dependent growth inhibition of c-MET-amplified SNU620, MKN45, Hs746T, SNU638 and KATO III cells with concomitant induction of apoptosis. Tepotinib treatment also significantly reduced expressions of phospho-c-MET, total c-MET, VEGFR2, Snail and c-Myc protein in SNU620, MKN45 and Hs746T cells. Especially, tepotinib significantly reduced the expressions of CD44 and PD-L1 in METex14 skipping mutated Hs746T cells. In contrast, this drug was only slightly active against KATO III and SNU638 cells. Migrations were more reduced in the tepotinib-treated group than in the control group. Conclusions: These data show the possibility that tepotinib may have therapeutic effects in c-MET-amplified GC and both high PD-L1 expression and an MET exon 14 skipping mutation, suggesting that clinical studies need to confirm the therapeutic effect.
Non-invasive cell-free DNA monitoring for predicting the response to neoadjuvant immunotherapy in locally advanced esophageal squamous cell carcinoma.
Authors: Wang Zhen , Wang Xin , Xinying Shi , Qin Jianjun , Li Yong , Zhang Yiqun , Wan Qianhui , Pei Zhihua , Wang Dongliang , Li Yin , He Jie 
Published: June 2022

e16040 Background: The combined modality therapy including neoadjuvant chemoradiotherapy has been selected as the standard care for locally advanced Esophageal squamous cell carcinoma (ESCC). However, the conclusive evidences to support the effectiveness of neoadjuvant immunotherapy for ESCC are rarely discussed. This study aims to investigate the molecular features of cell-free DNA (cfDNA) and the impact of their dynamic changes on the response to neoadjuvant immunotherapy in locally advanced ESCC patients. Methods: Twenty-four eligible locally advanced ESCC patients with received neoadjuvant immunotherapy were enrolled in this study. 7 patients achieved pathological complete regression (pCR) and the other 17 patients had non-pCR. The baseline, second and third blood samples (before neoadjuvant immunotherapy, at one month and two months after neoadjuvant immunotherapy, respectively) were collected from Cancer Institute and Hospital, Chinese Academy of Medical Sciences. Both cfDNA fragments and genomic DNA were extracted for enrichment of a customized panel covering exon regions of 599 genes. The dynamic analysis of gene alterations, which allows the monitoring of the response to neoadjuvant immunotherapy in locally advanced ESCC patients, were conducted based on multiple blood sampling strategy. Results: The most frequently mutated genes among all cases were TP53, KMT2D, CREBBP and KMT2B. MSI scores of both second and third blood samples were remarkablely higher than those in baseline blood samples (p = 0.002, 0.04). On the contrary, the TMB values and mean variant allele frequency (VAF) of second and third blood samples were significantly decreased compared with the baseline blood (TMB, p = 0.04, 0.03; mean VAF, p = 0.01, 0.02). Moreover, a decreasing trend of mean VAF was observed at the time-series blood samples from ESCC patients with pCR, while the mean VAF of ESCC patients with non-pCR declined in the blood samples from the second time point then increased in the blood samples from the thrid time point. Conclusions: The detection of dynamic changes of mean VAF could distinguish the pCR and non-pCR ESCC patients with neoadjuvant immunotherapy. These findings warrant further expanded prospective cohorts to validate.
Real-world treatment patterns and survival of U.S. patients receiving second-line anti-programmed cell death protein-1 therapy for advanced/metastatic esophageal squamous cell carcinoma.
Authors: Ahn Daniel H. , Sidel Michelle , Panattoni Laura , Sacks Naomi , Hernandez Jennifer , Villacorta Reginald 
Published: June 2022

e16042 Background: Current second-line (2L) therapies for patients (pts) with advanced/metastatic esophageal squamous cell carcinoma (adv/met ESCC), including docetaxel, paclitaxel and irinotecan, have demonstrated modest survival gains. The National Comprehensive Cancer Network added the use of anti-programmed cell death protein-1 (PD-1) therapies (e.g., pembrolizumab, nivolumab) in the 2L to their guidelines in 2020. A real-world evidence study of 2L therapy for adv/met ESCC patients reported a median (95% CI) overall survival (OS) of 201 (153-249) days but did not include recently approved anti-PD-1 agents. Other studies of 2L anti-PD-1 therapy relied on claims data without the ability to report survival. Limited studies exist for 2L ESCC real-world treatment patterns. Herein, we characterize the real-world treatment patterns and OS for a recent cohort of US pts initiating an anti-PD-1 2L therapy. Methods: Pts (≥ 18 years of age) from the United States diagnosed with adv/met ESCC and initiating an anti-PD-1 2L therapy between January 1, 2011 and February 28, 2021 were selected using the electronic health record (EHR)-derived de-identified Flatiron Health database. Pt characteristics and descriptive treatment patterns were reported. Duration of therapy (DoT; start of therapy until last administration) was computed and OS (start of therapy until death or last recorded medical activity) was estimated by the Kaplan Meier method. Results: 60 pts were included who initiated an anti-PD-1 2L therapy. At 2L initiation, the median age was 66 years, 65% were male, 53% were white, 82% had a history of smoking, and 53% had stage IV disease. The median DoT was 92 days and median OS was 303 days with variability across agents (Table) . Of the 60 pts, a total of 21 (35%) initiated 3L therapy (8 initiated an anti-PD-1; 13 initiated a non-anti-PD-1). Of the 39 (65%) pts who did not initiate a 3L therapy, 16 (41%) died within 60 days of the final 2L administration, 12 (31%) lacked 60 days of follow-up observation, and the remaining 11 (28%) patients had no further 2L treatment. Conclusions: Compared to prior real-world analyses, use of anti-PD-1 therapy in the 2L for patients with advanced/metastatic ESCC may be associated with survival gains over other approved non-anti-PD-1 therapies. However, future real-world studies are needed to directly compare PD-1 inhibitors with other 2L therapies.[Table: see text]