bluuebunny/crossref_metadata_2025 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]
The role of PRRX1 in esophageal cancer.
Authors: Guo Jinbao
Published: June 2022

e16046

Background: Recently, paired related homeobox 1 (PRRX1) was identified as a new EMT inducer that induces EMT in solid tumor. Interestingly, the functions of PRRX1 are significantly different, high expression of PRRX1 predicts less metastasis of breast cancer and a better prognosis. However, we observed the opposite relationship in gastric cancer, which was also reported in colorectal cancer and pancreatic cancer. While the function of PRRX1 in oesophageal cancer and whether PRRX1 induces EMT in oesophageal cancer metastasis have not been determined. Methods: One hundred primary oesophageal cancer tissue specimens were collected, immunohistochemical staining was performed to detect the expression of PRRX1. Cell proliferation, the migration and invasion were detected with different PRRX1 expression in oesophageal cancer cells. And the relationship between PRRX1 and Wnt/β-catenin pathway was also explained. Results: Regulation of PRRX1 expression might exert obvious effects on cell proliferation, especially the migration and invasion of oesophageal cancer cells. Moreover, silencing PRRX1 expression using a short hairpin RNA (shRNA) produced the opposite effects. In addition, when PRRX1 was overexpressed, inhibition of the Wnt/β-catenin pathway with XAV939 negated the effect of PRRX1 on EMT, whereas when PRRX1 was downregulated, activation of the Wnt/β-catenin pathway with LiCl impaired the effect on EMT. Conclusions: PRRX1 is expressed at high levels in oesophageal cancer specimens and is closely related to tumour metastasis in patients with oesophageal cancer. Additionally, PRRX1 induces EMT in oesophageal cancer metastasis through activation of Wnt/β-catenin signalling.
Adjuvant immunotherapy in patients with resected esophageal and gastroesophageal junction cancer: Real-world evidence from Nova Scotia.
Authors: Sheridan Margaret , Snow Stephanie Leann
Published: June 2022

e16047

Background: Post-operative immunotherapy (POI) with nivolumab has become the standard of care for eligible patients with esophageal and gastroesophageal junction cancers (EGEJC) who had pre-operative chemoradiation (POCRT) and definitive surgery. However, not all patients who receive POCRT are eligible for POI. Objective: The primary objective was to determine the proportion of patients who receive POCRT that are eligible for POI in a real-world population. Further, we aimed to identify the specific barriers to POI to determine factors which could be strategically addressed to maximize access to curative intent treatment. Methods: All patients residing in mainland Nova Scotia who received POCRT between July 2016 and April 2019 were analyzed. Disease, patient, and treatment characteristics were collected via chart review. The relative proportion of patients who (1) had definitive surgery, (2) were eligible to receive POI and (3) would have accepted POI were collected. The specific reasons for non-eligibility or refusal of POI were captured. Results: A total of 65 patients received POCRT during the study period. 44 of those went on to have definitive surgery. All 44 of these patients were then screened for eligibility to be enrolled in a trial of POI. 23 were eligible, but 12 declined trial enrolment. 21 were ineligible, with the most common reason being a pathological complete response (n=11). Of the 21 patients who did not undergo surgery, 12 were found to have new metastatic disease on pre-operative restaging and 9 were felt to be too frail. Conclusions: Only 35% of patient receiving POCRT were eligible for POI. This is important real-world data when planning allocation of resources and adapting health care budgets for novel treatments and indications.
Real-world effectiveness of anlotinib plus PD-1 inhibitors as chemo-free therapy in advanced or metastatic esophageal cancer.
Authors: Wang Junsheng , Hong Yonggui , Wu Tao , Lu Ping , Chang Zhiwei , Liang Wei , Zhang Guifang
Published: June 2022

e16052

Background: Immunotherapy, particularly with anti-PD-1/PD-L1 antibodies, has shown therapeutic efficacy in various malignancies. Compared with chemotherapy, anti-PD-1 antibody monotherapy improved the median overall survival in advanced or metastatic esophageal cancer. The combination of an anti-PD-1/PD-L1 antibody with an angiogenesis inhibitor has shown efficacy in many cancers which including esophageal cancer. The purpose of this study is to investigate the efficacy and safety of anlotinib plus PD-1 inhibitors as chemo-free therapy during the treatment of esophageal cancer in the real world setting. Methods: This prospective, multicenter real-world study (NCT04966611) evaluated the efficacy and safety of anlotinib plus PD-1 inhibitors in the chemo-free therapy setting for advanced or metastatic esophageal cancer patients (pts). Primary endpoint was evaluation of PFS (progression-free survival), and secondary endpoints included ORR (objective response rate), DCR (disease control rate) and OS (overall survival). The response to treatment was evaluated according to RECIST version 1.1. In addition, adverse events were evaluated by CTCAE v5.0. Results: Between May 2020 and Dec 2021, 50 pts were enrolled. 45 comprised the evaluable population. In the full analysis set, 44 had squamous cell and 1 patient had adenocarcinoma histology. 29 (64.4%) of 45 pts were male. 10 (22.2%) had an ECOG performance status of 0, 32 (71.1%) status of 1 and 3 (6.7%) status of 2. Twenty (44.4%) pts had distant metastases and 29(64.4%) pts had comorbidities. 15 pts had previously used anti-PD-1/PD-L1 antibody or vascular targeting drugs, of which 5 cases had combined the two drugs. Among all evaluable pts, 5(11.1%) pts received first-line, 27(60.0%) second-line and 13(28.9%) third & above line therapy. Among all pts, 1 patient achieved complete response (CR), 16 pts partial response (PR), 25 pts stable disease (SD), illustrating an ORR of 37.8% and a DCR of 93.3%. In the first line therapy, ORR was 60.0%, DCR was 100%.In the second line therapy, ORR was 37.0%, DCR was 96.3%. In the third & above line, ORR with 30.8%, DCR with 84.6% was observed. Median PFS was not reached. Treatment related adverse events (trAEs) were reported in 24 pts(53.3%). No patient had grade 3 or more trAEs. Conclusions: Anlotinib plus PD-1 inhibitors in chemo-free therapy for advanced or metastatic esophageal cancer was active and showed excellent tumor response and was generally well tolerated. Further investigation is required in a larger real-world cohort to validate the benefit of anlotinib plus PD-1 inhibitor in esophageal cancer. Clinical trial information: NCT04966611.
Detection of targetable fusion alterations in gastric cancer in the Chinese population.
Authors: Liu Zhenhua , Zhu Bowen
Published: June 2022

e16061

Background: Despite a decreasing incidence and mortality globally, gastric cancer (GC) remains a main threat to public health, especially in China. Consistently, drug therapy is a big challenge for gastric cancer. Although HER2-directed therapy and immune checkpoint inhibitors have achieved great success, other valid targeted drugs are required to develop. Targeted drugs of NTRK gene fusion have been approved in solid tumors including GC by FDA. Moreover, FDA has granted Zenocutuzumab fast-track approval for patients with NRG1 gene fusion in solid tumors. However, in China, gene fusion and functional characterization have not been reported to date in detail. Methods: In order to estimate the fraction of patients who may benefit from targeted drugs, we retrospectively analyzed the fusion alterations in gastric cancer tissue samples from 955 Chinese patients. Remarkably, as fusion partners, all genes included fusion analysis possess experimental or approved drugs. The clinicopathological characteristics were retrieved from the medical records in hospital. Chi-square analysis was used to investigate the relationship of gene fusions with drivers mutations, MSI, TMB and MMR. Results: We found 2.82% (27/955) of patients harboring fusion genes, including MET, ROS1, ALK, FGFR1/2, NTRK, BRAF, EGFR and so on. Among them, EML4-ALK, EWSR1-FLI1 and EGFR-SEPTIN14 have been described in other studies, but 88.9% (24/27) fusion genes are previously unreported. Sequencing results indicate that fusion genes are significantly enriched in patients with ERBB2 gene amplification. In addition, there is no obvious correlation between the positive rate of gene fusion and clinical features including age and gender. Similarly, MSI status, TMB and MMR are included for correlation analysis with gene fusion. Unfortunately, the results are not statistically significant. Conclusions: Our work characterizes the landscape of targetable fusion alterations in gastric cancer in the Chinese population and investigates that targetable fusion testing should be advised to patients with disease progression after receiving standard therapy.
Camrelizumab combined with SOX in the first-line treatment of unresectable advanced or metastatic gastric/gastroesophageal junction (G/GEJ) adenocarcinoma: A single-arm, prospective, and open-label clinical study.
Authors: Liu Wenlou , Qin Xiaobing , Zhao Yang , Ge Yan , Tang Juanjuan , Wang Hongmei , Han Zhengxiang
Published: June 2022

e16090

Background: First-line chemotherapy for advanced human epidermal growth factor receptor 2 (HER2)-negative gastric/gastroesophageal junction (G/GEJ) adenocarcinoma results in median overall survival (mOS) < 1 year. The programmed death (PD)-1 inhibitor provided superior OS in advanced G/GEJ adenocarcinoma combind with chemotherapy. However, the continuous explore about PD-1 inhibitors of first-line treatment with G/GEJ adenocarcinoma patients is promising. Camrelizumab, an anti-PD-1 monoclonal antibody, has been shown to have synergistic antitumor effects in the treatment of G/GEJ adenocarcinoma patients. We aimed to evaluate the safety and efficacy of camrelizumab combined with SOX in the first-line treatment of advanced G/GEJ adenocarcinoma. Methods: In this study (ChiCTR2000029691), eligible patients were diagnosed as unresectable advanced, postoperative recurrent ormetastatic, HER2-negative G/GEJ adenocarcinoma, and treatment-naive with chemotherapy, VEGFR2 inhibitors or PD-1/PD-L1 inhibitors. Patients received camrelizumab (200 mg, I.V., d1) and SOX regimen (oxaliplatin, 130 mg/m2, d1; S-1, 20mg/m2, bid, d1-14) every 3 weeks, until disease progression, intolerable toxicities, or physician/patient withdrawal. The safety and efficacy were assessed by investigators per CTCAE v5.0 and RECIST v1.1, respectively. The primary endpoint was progress free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Results: From March 30, 2020 to March 18, 2021, 27 patients had been enrolled to receive therpy with camrelizumab and SOX regimen. The patients were characterized with a median age of 60 years (range 26-79), 88.9% males and 11.1% females, 40.7% GEJ adenocarcinoma, 88.9% lymph node metastasis, 25.9% liver metastases, and 18.5% of patients had a history of tumor-related surgery. As of Nov 2, 2021, with a median follow-up of 8.8 months (range, 0.9-16.8), safety and efficacy were assessed in 20 evaluable patients, with overall response of 8 partial response (PR) and 9 stable disease (SD). Confirmed ORR and DCR were 40.0% (95% CI, 20.0%-63.6%) and 85.0% (95% CI, 61.1%-96.0%), respectively. The median PFS and OS were 12.7 months (95% CI, 4.9-20.5) and 16.8 months (95% CI, 3.5-30.0), respectively. Grade 3-4 treatment-related adverse events occurred in 18.5% of patients, with anemia and neutropenia ranking the most frequent. No new safety signals was identified. Conclusions: Camrelizumab combined with SOX was well tolerated and demonstrated encouraging efficacy for previously untreated with chemotherapy, VEGFR2 inhibitors or PD-1/PD-L1 inhibitors, unresectable advanced or metastatic, HER2-negative G/GEJ adenocarcinoma. Clinical trial information: ChiCTR2000029691.
Clinical and molecular characteristics of advanced esophageal/GEJ cancer with brain metastasis.
Authors: Liang Kai-li , Feliciano Josephine Louella , Marrone Kristen , Murray Joseph Christopher , Tackett Sean , Hales Russell K. , Voong K. Ranh , Battafarano Richard James , Yang Stephen , Broderick Stephen , Ha Jinny Suk , Forde Patrick M. , Brahmer Julie R. , Lam Vincent K.
Published: June 2022

e16092

Background: Brain metastasis (BRM) in gastroesophageal (GE) cancer is uncommon, but contributes to poor prognosis and significant symptom burden. While HER2 overexpression has been suggested as a potential driver of BRM, clinicopathologic and molecular determinants of BRM in GE cancer and their impact on clinical outcome remain incompletely understood. Methods: We retrospectively analyzed clinicopathologic data from 323 advanced esophageal/GEJ patients (pts) at Johns Hopkins from 2003 to 2021. Univariate and multivariate logistic regression were performed to investigate the association between several clinical and molecular features and the occurrence of BRM, with particular focus on HER2 overexpression (by IHC and FISH) and PD-L1 expression (by IHC) as measured by the combined positive score (CPS). Overall survival was estimated using the Kaplan-Meier method. Results: Median age was 64 and most pts were white (90.4%). Tumors were 73.7% esophageal primary, 82.7% adenocarcinoma, 43.8% HER2+, and 11.1% CPS ≥ 1. Cumulative incidence of BRM in overall cohort and within HER2+ subgroup was 14.6% (47 pts) and 25.4% (16 pts), respectively. Pts with BRM (not already present at time of stage IV diagnosis) had median onset of 10.8 months. Seventeen (36.2%) pts had a solitary brain lesion and 10 (21.7%) were asymptomatic. On univariate analysis, adenocarcinoma and HER2 overexpression were associated with increased risk of BRM (OR 3.45; 95% CI 0.09-0.96; p = 0.043 and OR 2.72; 95% CI 1.11-6.67; p = 0.028, respectively). Notably, the HER2 association was strengthened when HER2 equivocal tumors were re-classified as positive in an exploratory analysis (OR 3.55; 95% CI 1.38-9.14; p = 0.009). Adenocarcinoma and HER2 overexpression were collinear in the multivariate model. In pts with BRM, OS was improved in HER2+ pts (16.72 months; 95% CI 12.3-21.1 months; log-rank p = 0.039 and OR 0.33; 95% CI 0.11-0.99; Cox regression p = 0.049). CPS and primary tumor location were not associated with increased BRM. Conclusions: HER2 overexpression identifies an esophageal/GEJ molecular subtype that is significantly associated with increased risk of BRM; though with improved OS (compared to non-HER2+ BRM) and later onset CNS progression, likely reflecting durable extra-CNS control on targeted systemic therapy and a potential HER2+ subgroup with relatively indolent biology. Prevalence of asymptomatic and solitary brain lesions supports increased brain surveillance for this population.
Comparative effectiveness of trimodal therapy versus definitive chemoradiation in older adults with locally advanced esophageal cancer.
Authors: Gaber Charles , Shaheen Nicholas J. , Edwards Jessie K. , Sandler Robert S , Nichols Hazel , Sanoff Hanna Kelly , Lund Jennifer Leigh
Published: June 2022

e16093

Background: The comparative effectiveness of trimodal therapy versus definitive chemoradiation for older adults with locally advanced esophageal cancer is uncertain. Only two randomized trials have considered this comparison, and older adults and patients with adenocarcinomas were underrepresented. Older adults have greater frailty and may not benefit from adding surgery to chemoradiation. Methods: A cohort of adults 66-79 years of age diagnosed with incident locally advanced esophageal cancer between 2004 and 2017 was identified using the Surveillance Epidemiology and End Results-Medicare database. We used observational data to emulate a hypothetical trial comparing trimodal therapy and definitive chemoradiation. Outcomes included overall mortality, esophageal cancer-specific mortality, functional adverse events, and healthy days at home. Results: The study population included 1,240 individuals with adenocarcinomas and 661 with squamous cell carcinomas. Amongst older adults diagnosed with adenocarcinomas, the five-year risk of mortality was 73.4% (95% CI: 69.1–77.4) in the trimodal therapy group and 83.8% (95% CI: 78.6–87.2) in the definitive chemoradiation group (RR= 0.88, 95% CI: 0.82–0.95). Amongst older adults diagnosed with squamous cell carcinomas, the five-year risk of mortality was 62.6% (95% CI: 50.9–73.5) in the trimodal therapy group and 72.3% (95% CI: 67.6–76.3) in the definitive chemoradiation group (RR= 0.87, 95% CI: 0.70–1.01). Results for all outcomes are presented in the Table. Conclusions: Trimodal therapy was associated with lower mortality than definitive chemoradiation. The benefits were smaller than suggested by prior observational studies. These findings can be used with clinical expertise and patient preferences to enhance shared decision-making. [Table: see text]
Clinical performance of a liquid biopsy test based on the detection of multiple DNA methylation biomarkers for early detection of gastrointestinal cancers.
Authors: Ma Yong , Zhao Guodong , Wang Kai , Song Lishuang , Xiong Shangmin , Li Hui , Chen Guangxia , Pei Bing , Shen Xizhong , Fei Sujuan , Zheng Minxue
Published: June 2022

e16096

Background: Gastrointestinal cancers (colorectal cancer, gastric cancer and esophageal cancer) are the most prevalent malignant tumors in China, resulting in 975,537 new cases and 958,675 deaths in 2020. Currently, the gold standard for the early detection of these cancers remains to be gastrointestinal endoscopy. However, the invasiveness, low throughput and high cost of these procedures have prevented its wide acceptance by Chinese population. The objective of this study was to develop a liquid biopsy test based on the detection of multiple DNA methylation biomarkers (SpecGastro test) and evaluate its clinical performance for early detection of gastrointestinal cancers. Methods: Two hundred and eighty-two gastrointestinal cancer patients (98 colorectal cancers, 136 gastric cancers and 48 esophageal cancers) and 195 control subjects were included. Ten milliliters of peripheral blood was drawn and 3.5 mL plasma was separated for cell-free DNA extraction and bisulfite conversion. The converted DNA was subsequently examined by SpecGastro test, a multiplex qPCR assay that detected six methylation biomarkers and one internal control. Results: Overall sensitivity for SpecGastro test was 76.6% (95% CI: 71.1-81.3%) with a specificity of 89.2% (95% CI: 83.8-93.1%). Sensitivities for colorectal cancer, gastric cancer and esophageal cancer were 87.8% (95% CI: 79.2-93.2%), 69.9% (95% CI: 61.3-77.3%) and 72.9% (95% CI: 57.9-84.3%), respectively. A high AUC of 0.903 (95% CI: 0.873-0.928) indicated that SpecGastro test distinguished gastrointestinal cancer patients from control subjects with high accuracy. Conclusions: Our analysis demonstrated the utility of SpecGastro test to detect three types of gastrointestinal cancers with high sensitivity and specificity. These results supported the feasibility of this blood-based SpecGastro test as a complementary tool to the existing single-cancer early detection tests.
PRO-based symptom management versus usual care for patients with gastric and esophageal cancer who undergone previous surgery: A randomized controlled trial.
Authors: He Yifu , Wu Shusheng , Ding Conglan , Fan Liyuan , Ke Lihong , Yan Ying , Li Mengge , Luo Huiqin , Hu Xiaoxiu , Niu Jiayu , Li Huimin , Xu Huijun , Chen Wenju , Cao Lulu
Published: June 2022

e16104

Background: In China, the incidence of gastric cancer and esophageal cancer ranks second and third, respectively. These patients often suffer from malnutrition, anorexia and gastroesophageal reflux, which have a serious implication on their subsequent treatment. However, due to the specificity of the current medical situation in China and the heavy treatment workload of clinicians, there is no efficient and easy way to manage the symptoms of these patients. Methods: Subjects were randomized in a 1:1 ratio after enrollment into the Patient-Reported Outcome (PRO) -based symptom management group and the usual care group. The PRO group were assessed for anorexia, gastroesophageal reflux, nutritional status, BMI in the hospital before each cycle of chemotherapy via an electronic data platform. The doctors responded the assessment results and provided interventions, including advice for home care, drug prescription, and telephone follow-up, before patients are discharged from the hospital. Patients were assessed and managed every 3-4 weeks at the time of return for chemotherapy during 16 weeks. Patients in the usual care group underwent symptom assessment only the first and the 16th weeks, during which the surgeons only managed the symptoms with usual care modalities. The primary endpoint is number of symptoms at the 16th weeks and the secondary endpoint are the incidence of each symptom at the 16th weeks. Results: The interim results of the trial is reported. From Apr 2021 to Dec 2021, 55 pts completed the clinical observation, including 25 pts in the PRO group and 30 pts in the usual care group. The number of overall symptoms in the PRO group was significantly lower than in the usual care group (1 (0-1.5) vs 2 (1-3)). The incidence of nutrition risk (28.0% vs 56.7%), anorexia (24.0% vs 60.0%) and gastroesophageal reflux(8.0% vs 50.0%) in the PRO group was significantly lower than that in the usual care group, and there was no statistically significant difference about underweight (defined: BMI<18.5, 24.0% vs 36.7%) and depression (0.0% vs 6.7%). Conclusions: Compared to usual care, nutritional risk, anorexia, and GERD rates were effectively controlled in patients with previously surgically resected gastric and esophageal cancers through 16 weeks of patient-reported outcome based symptom management, with assessment scores confirming the same results, providing clinicians with an easy-to-operate and effective means of symptom management. Clinical trial information: ChiCTR2100041701. [Table: see text]
Racial parity in esophageal cancer treatment at an integrated healthcare system.
Authors: Hsu Diana S. , Banks Kian C , Kwak Hyunjee V. , Chang Amber , Truong Thach-Giao , Velotta Jeffrey B.
Published: June 2022

e16105

Background: This study evaluates survival outcomes of esophageal cancer patients treated at a large, tertiary care integrated healthcare system and whether there are differences based on race. Methods: We conducted a retrospective study from January 2010 to December 2019 among patients at Kaiser Permanente Northern California (KPNC). Self-reported racial ethnic groups included Caucasian, African American, Hispanic, Asian, and Other. Kaplan Meier and Cox regression analyses were used to evaluate differences in race, age, stage, and treatment utilization in relation to overall survival. Results: A total of 1,692 patients were diagnosed with esophageal cancer. Of these, 11% were Asian, 8.1% were Hispanic, and 6% were African American. Caucasians had the oldest mean age at diagnosis, 70.2 years, and the Hispanics had the youngest mean age at diagnosis, 64.6 years (p < 0.001). There were no statistically significant differences in stage at time of diagnosis between race groups (p = 0.41). Adenocarcinoma was more common in Caucasians and Hispanics, while squamous cell was more common in African Americans and Asians (p < 0.001). Treatments received by the patients included, surgery, chemotherapy, radiation, and a combination thereof (multimodal). There was no statistical significance among the races in treatment modalities received, including multimodal therapy (p = 0.12-0.66). The difference in mean overall survival (OS) between the race groups was not statistically significant. Kaplan-Meier survival analyses were performed and demonstrated statistically significant differences in mean OS between the two histologies, with adenocarcinoma having the highest survival of 33.9 months (p < 0.001). Conclusions: We identified racial parity in survival outcomes and treatment utilization for esophageal cancer patients who were treated at a large integrated healthcare system where patients have equal access to care.[Table: see text]