bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pooled analysis of POLE-mutant colorectal cancer characteristics.
Authors: Li Sharon , Panda Anshuman , Ciner Aaron , Ganesan Shridar , Hochster Howard S. 
Published: June 2021

e15515 Background: Colorectal cancers (CRC) with pathogenic mutations in POLE (mPOLE) represent a unique subgroup with distinct clinical and molecular features and may exhibit a robust response to immune checkpoint blockade. Due to low prevalence, clinical features of this subgroup remain incompletely characterized. Methods: We utilized data from the Oncology Research Information Exchange Network (ORIEN) , using the Total Cancer Care (TCC) protocol in 18 centers across the US, to identify mPOLE CRC cases through October 2020. Prevalence, genomic and clinical features of mPOLE CRC within ORIEN were compared with other public databases, including AACR GENIE (version 8.0) , TCGA pan-cancer atlas, and a cohort from DFCI via cbioportal . Given the small sample size of mPOLE patients in each cohort, we pooled available data to compare characteristics of mPOLE CRC with CRC cases without pathogenic mutations in POLE (wtPOLE). Results: Detailed results are illustrated in the table. Out of 1564 CRC patients in ORIEN, 140 patients (9%) had POLE mutations, but only 11 patients (<1%) had pathogenic POLE mutations, compared to <2% in TCGA, <1% in DFCI, and <0.5% in the AACR GENIE cohorts. mPOLE CRC was associated with significantly higher tumor mutational burden and lower copy number alterations in all cohorts with data. In ORIEN, median age at diagnosis was significantly lower in mPOLE patients and at least 5 years younger than mPOLE patients from other cohorts. No other variable was statistically significant within ORIEN. When available clinical data from all cohorts were pooled, mPOLE was significantly associated with male sex, younger age at diagnosis, and early stage (I/II) disease. Conclusions: The ORIEN data set showed <1% patients with pathogenic POLE mutations. When pooled with the available public data sets, we see emergence of a unique clinical phenotype. Additional outcome data from ORIEN TCC database will be reported. We acknowledge the participation and assistance of the ORIEN investigators, with thanks. wtPOLE vs mPOLE in pooled and individual large cohort studies.[Table: see text]
Analysis of the relationship between different prognosis factors in patients with advanced colon cancer and progression-free survival.
Authors: Richardet Eduardo , Magi Ignacio , Acosta Luciana Paola , Ferreira Maria gimena , Molina Matias , Richardet Martin Eduardo 
Published: June 2021

e15518 Background: Colon tumors are a heterogeneous group of disease. As a result of the accumulation of different genetic and epigenetic alterations, the mutation of the RAS, BRAF oncogene and microsatellite instability stands out. A new line of research are immunological and inflammatory factors, the infiltrating lymphocytes of the tumor stroma (TILs) and the neutrophil to lymphocyte radio (NLR) have been studied by our work team. We understood could that these factors were associated with the survival rate in our patients. The main objective of this reseach is to determine the relationship between NLR and progression-free survival (PFS) in patients with advanced colon cancer. Secondary objective is to determine the relationship between the location of the primary tumor, RAS status, TILs, and PFS. in the same group of patients. Methods: A total of 93 medical records of patients with advanced colon cancer was analyzed. Those pts who had recieved first-line chemotherapy treatment with a FOLFOX scheme plus a monoclonal antibody were included. All patients had to have a minimum follow-up of 12 months. Regarding NLR, the patients were classified into two groups: high ( = > 4) and low ( < 4). Four TILs cut-off points were determined: > 40% intense; between 11-40% moderate, 1-10% mild, and 0% absent, which were group into two categories: intense and moderate; slight and absent. Localization was divided into left and right, and KRAS status was divided into mutated and wild-type (WT). PFS was calculated using the Kaplan-Meier test. Results: The median PFS of the general population was 8.74 (7.39-11.07) months. The median PFS was 9.86 (7.82-13.41) vs 5.09 (4.43-10.84) months for low and high NLR respectively, with statistical significance (p: 0.01). When the percentage of patients without progression after one year of treatment was analyzed, the difference was 45% vs 14% in favor of NLR < 4 on ≥4, this difference was also statistically significant (p: 0.02). PFS in relation to TILs after one year of follow up was 33% (8.61 months) for moderate-intense infiltrate vs 30% of mild-absent (7.10 months). PFS was 9.79 months for KRAS WT pts vs 7.82 months for mutated KRAS. In terms of location, PFS was 9.79 months for the left colon vs 8.28 months for the right colon. These factors did not have a statistically significant difference. Conclusions: The results of the study show how NLR < 4 is a prognostic factor with a positive impact on PFS. It should be noted that the median survival rates were numerically higher in moderate-intense vs mild-absent TILs, also in KRAS WT vs mutated and in left vs right location. It should also be noted that the possibly there was not a statistically significant difference between them due to the limited number of patients per what we will continue working on in the recruitment and analysis of these patients.
VEGFR2 expressions in Th1 and CD8+ cytotoxic T lymphocytes (CTL) in colon cancer patients.
Authors: Artac Mehmet , Ceylan Ayca , Karakurt Eryılmaz Melek , Araz Murat , Karaagac Mustafa , Artac Hasibe , Emiroglu Melike 
Published: June 2021

e15535 Background: VEGF receptors have an important role for inhibiting adaptive immun response in colon cancer. Therefore, we analyzed VEGF receptors in circulating T cell subsets according to stage in colon cancer patients. Methods: The prospective study group consisted of 50 patients with histologically confirmed colon cancer and 30 person without any cancer history as a control group. Peripheral blood specimens were collected from the patients after the diagnosis before inducing chemotherapy and radiotherapy. Patients with active infections or autoimmune disorders, who were treated with steroids and antibiotics in the last four weeks before the study enrollment were excluded from the study group. VEGFR2 expressions in circulating T cell subsets (Th1, Th2, Th17, CTL) were analyzed by flow cyctometry. Results: Age and gender were not different between the all study groups. Mean circulating CD4+ folicullar cells were less in colon cancer patients (9.54%±3.99) than the control group (12.03%±4.34), (p < 0.01). Mean circulating CD8+ follicular cells were higher in metastatic colon cancer (n = 26) 2.48% ± 1.68, than the non-metastatic colon cancer patients (n = 24) 1.63% ± 1.37, (p = 0.02). Mean VEGFR2 expressions in Th1 cells were higher in colon cancer patients 248.8 (Mean Flourescein intensity-MFI) than the control group 224.6, (P = 0.006). Mean VEGFR2 expressions in CTL were higher in colon cancer patients (381.8) than the control group (284.7), (p < 0.001). PD-1 expressions were not different between the colon cancer patients and the control group in all circulating T cell subsets. Mean VEGFR2 expressions in Th17 cells were higher non-metastatic colon cancer patients than the metastatic colon cancer patients (326.5 and 268.4 MFI, respectively, p = 0.02). Conclusions: VEGFR2 expressions are increased in circulating Th1 and CTL subsets in colon cancer patients. Whereas PD-1 expressions were not different in circulating T cell subsets than the control. VEGFRs may play an important role for the inhibition of circulating T cell subsets in colon cancer.
Efficacy, treatment modalities, and safety of regorafenib in Chinese metastatic colorectal cancer patients: A multiple centers real-world study.
Authors: Jiang Zhichao , Sun Yongkun , Zhang Wen , Liu Ning , Qiu Wensheng , Jiang Tao , Li Sheng , Sun Ning , Li Xiaoyou , Zhu Liangjun , Liu Zimin , Zhou Ai-Ping 
Published: June 2021

e15569 Background: For patients with refractory metastatic colorectal cancer (mCRC) treatment with regorafenib improved the overall survival (OS) in two phase 3 trials. Regorafenib has been recognized as a standard third line treatment in mCRC. However, the efficacy and safety of regorafenib in real world for Chinese patients is lacking. Methods: Patients of mCRC treated with at least one cycle of regorafenib (40, 80, 120 or 160mg OD for 21 days, as a 28-day cycle) from August 2017 to June 2020 in three Chinese medical centers were enrolled. Data of demographic, treatment, dosimetry, safety and survival was collected retrospectively. The primary endpoint was OS. Secondary endpoints were progression free survival (PFS), objective response rate (ORR), disease control rate (DCR) and the incidence of adverse events (AEs). Results: 372 patients were enrolled, of whom 266 (71.5%) accepted regorafenib alone and 106 (28.5%) received combination therapy with regorafenib. In these patients, 75 (20.16%) and 275 (73.9%) patients received regorafenib as third or higher line treatment. Starting dose was 160mg in 93 (25.0%) patients, 120mg in 74 (19.9%) patients, 80mg in 142 (38.2%) patients and 40mg in 7 (1.9%) patients. The maintenance dose was confirmed in 236 patients. Among them, 111 (46.6%) and 75 (31.8%) accepted 80 and 120mg as the last daily dose. Only 50 (21.2%) patients could receive 160mg as a long-term therapy. Median follow-up time was 15.2 months. ORR and DCR were 3.8% and 55.3%. The mPFS was 3.1 months (95%CI: 2.50-3.53) and mOS was 10.2 months (95% CI: 9.27-11.93) . The mOS of 80, 120 and 160mg last daily dose were 10.5, 14.1 and 14.3 months, respectively. Patients received regorafenib in combination with other drugs including chemotherapy or PD-1 inhibitor had longer survival compared with regorafenib alone with mOS of 15.5 (95% CI: 10.1-19.0) and 9.7 months (95% CI: 7.8-11.0) (p = 0.004). The mOS of patients developed lung metastasis and the counterpart with liver metastasis was13.3 versus 9.7 months. The common AEs were anemia (26.1%), hyperbilirubinemia (25.3%), liver injury (24.7%), thrombocytopenia (18.0%) and recorded hand-foot skin reaction (HFSR) (19.6%). The most common grade 3-4 AEs included hyperbilirubinemia (3.5%), recorded HFSR (3.5%), anemia (2.2%) and thrombocytopenia (1.1%). Due to most patients was reviewed in clinic, some data of AEs was missing or incomplete. Conclusions: In the real world, regorafenib showed promising efficacy and manageable toxicities in Chinese patients with refractory mCRC. The dose of 120mg of regorafenib seemed to have a similar survival benefit compared with 160mg. In addition to a better tolerance, 120mg may be a more suitable dose for Chinese mCRC patients. Clinical trial information: NCT04735991. [Key words] Colorectal cancer; Regorafenib; Real world
Retrospective pilot study of regorafenib combined with ICIs in the third-line treatment of advanced colorectal cancer.
Authors: Zhang Hangyu , Zheng Yi , Tong Zhou , Liu Lulu , Zhu Xudong , Fu Qihan , Bao Xuanwen , Dai Xiaomeng , Fang Weijia , Zhao Peng 
Published: June 2021

e15582 Background: An increasing number of patients with advanced colorectal cancer tend to receive third-line treatment. Although there are several treatment options, concerns about efficacy and adverse events still remained. Regorafenib seems to enhance the effect of immune checkpoint inhibitors (ICIs) by modulate tumor microenvironment. In the absence of stage III clinical trial data, the real-world study might show certain clinical value. Methods: From Aug 2019 to June 2020, 23 advanced MSS colorectal cancer patients underwent third-line treatment of regorafenib combined with ICI. All patients received regorafenib 80 mg QD for 21 days, as a 28-day cycle, combined with ICIs until disease progression or intolerable adverse events. We retrospectively collected the overall response data, survival data and adverse events data from these patients. Results: The characteristics of all 23 patients is shown in the table. All patients had received at least 2 lines of prior systemic chemotherapy, the median time from diagnosis to third-line treatment was 31 months. The overall response rate was 26% (6/23), including one complete response. Almost all the responders were male (5/6) and with pulmonary metastasis (5/6). The disease control rate was 60% (14/23). The progression free survival ranges from 0.69 month to 19.3 months (median 4.8 months), with 6 patients continued response and constantly treatment. Duration of response range from 6.4 months to 19.4 months. Serious adverse events were hepatitis occurred in two patients and lead to the termination of subsequent anticancer therapy, which was considered to be related to immunotherapy. Conclusions: Regorafenib combined with ICIs might favor a certain group of advanced colorectal cancer patients, with a acceptable response rate and comparatively long duration of response. Interestingly, this retrospective pilot study was in consistence with that of REGONIVO trials to some extent for that the male patients with pulmonary metastasis appeared to response better. Key words: colorectal cancer; regorafenib; immune check point inhibitors Clinical characteristics of 23 patients.[Table: see text]
A study on the genomic alterations of transformation from colorectal adenoma to colorectal cancer.
Authors: Chen Qingjian , Yang Pan , Luo Linna , Fan Wenhua , Wei Chen , Zhao Qi , Luo Huiyan 
Published: June 2021

e15607 Background: Colorectal cancer is one of the most common malignancies worldwide. Approximately 85% of colorectal cancers are thought to result from adenoma. However, the molecular mechanism of adenoma transformation into colorectal cancer is still unclear. Methods: Ninety-nine adenoma patients aged from 25 to 78 years old were enrolled in this study. We collected tissue sample from each patient and 77 matched blood samples. Pathological subtypes included tubular villous adenomas, villous adenomas, tubular adenomas, high-grade intraepithelial neoplasia, and polyps. Eighty-one stage I colorectal cancer patients (CRC I) were also enrolled in this study. All samples underwent Next-generation sequencing with a panel of 405 cancer related genes. Results: Mutational profiles of adenoma and CRC I patients were compared. The top 5 most frequently mutated genes in adenoma were APC (71%), KRAS (41%), ATM (33%), RIF1 (31%), SYNE1 (28%). While in CRC I patients, top 5 mutated genes were APC (78%), TP53 (57%), TTN (35%), KRAS (33%) and TCF7L2 (22%). There were significant differences between TP53 and TTN by chi-square test. The frequency, number and TMB of mutations in stage I colorectal cancer patients were significantly higher than those in various adenoma subtypes. Stage I colorectal cancer patients have more mutated genes enriched in the Wnt and Notch pathways than adenoma patients. We analyzed mutation signatures in CRC I and adenoma patients, and CRC I were more focused on mutation signatures of mismatch repair such as signature 1, signature 6, signature 10, and signature 15. A total of 391 mutations were identified in tissue samples, while 130 mutations were found in plasma cell-free DNA, with 116 mutations shared between them. The two genes with the highest consistency between tissue and blood were PAX7 and KMT2D. Conclusions: TP53 and TTN are associated with the transition from CRC I to adenoma, and Wnt and Notch pathways may also be involved. PAX7 and KMT2D mutations frequently found in adenoma tissue and blood cfDNA demonstrate the diagnostic potential of these two genes in clinic.
Update results of paclitaxel and cisplatin in combination with anlotinib as first-line regimen for patients with advanced ESCC: A multicenter, single-arm, open-label phase Ⅱ clinical trial.
Authors: Wang Junsheng , Wu Tao , Luo Suxia , Li Ning , Hong Yonggui , Guo Yanzhen , Cheng Yufeng , Li Baosheng 
Published: June 2021

e16013 Background: Paclitaxel combined with cisplatin regimen has been the standard first-line therapy in advanced Esophageal Squamous Cell Carcinoma (ESCC) for almost two decades. However, the 5-year survival rate was only 4.8% in advanced ESCC. Therefore, more effective therapeutic treatments were needed to prolong the survival urgently. Anlotinib was demonstrated to be an effective second-line monotherapy for patients with advanced or recurrent ESCC in China. And the preliminary results of our trial had been reported in 2020 ESMO (Abs 1448) and 2021 ASCO-GI Symposium (Abs 181). Consequently, this study was to investigate the efficacy and safety of paclitaxel and cisplatin combined with anlotinib as first-line therapy in advanced ESCC and report the update results regularly. Methods: Pts with previously untreated metastatic or unresectable, locally advanced ESCC, who had not received (neo) adjuvant therapy/radical surgery within 6 months were recruited in this study. Eligible patients were given paclitaxel (135mg/m2, iv, q3w) and cisplatin (60̃75mg/m2, iv, d1̃3, q3w) plus anlotinib (10mg, po, d1̃14, q3w) for 4̃6 cycles as initial therapy. For those who did not have disease progression, maintenance treatment was treated with anlotinib monotherapy (10mg, po, d1̃14, q3w) until progression or unacceptable toxicity. The tumor response was assessed by investigator according to RECIST version 1.1 criteria using computed tomography scans every two cycles. The predefined sample size was 47. The primary endpoint was PFS and secondary endpoints included safety, ORR, DCR and DOR. Results: From Oct 2019 to Dec 2020, a total of 45 patients were enrolled. Among 34 pts who were available for efficacy and safety evaluation. there were 1 confirmed CR (2.9%), 26 confirmed PR (76.5%), 2 unconfirmed PR (5.9%) and 5 SD (14.7%). Consequently, ORR was 79.4% (95%CI: 62.1̃91.3) and DCR was 100.0% (95%CI: 89.7̃100.0). At the data cut-off date, 11 patients discontinued treatment due to PD, the preliminary prognostic result indicated that the median PFS of the 34 patients was 9.76 months (95%CI: 8.44-13.08). And the median OS was not yet available. Additionally, safety profile exhibited that the common drug-related adverse events were myelosuppression, gastrointestinal reaction, fatigue, hypertension, constipation, hypokalemia, hepatotoxicity and hemoptysis. And the common grade ≥3 adverse events were myelosuppression (20.6%), hypertension (8.8%), nausea and vomit (5.9%), fatigue (5.9%) and hypokalemia (5.9%). Conclusions: The update results suggested that the regimen of paclitaxel and cisplatin combined with anlotinib as first-line therapy for advanced ESCC exhibited encouraging efficacy and tolerable safety profile. And the conclusions needed to be confirmed in trials continued subsequently. Clinical trial information: NCT04063683.
CO-STAR: Surgical conversion feasibility trial of sintilimab (PD-1 inhibitor) combined with Nab-PTX, S-1 and apatinib for the first-line treatment of stage IV gastric cancer (GC).
Authors: Xue Qiang , Wang Baogui , Wang Xiaona , Ding Xuewei , Liu Yong , Wang Xuejun , Liu Ning , Zhan Hongjie , Ke Bin , Li Bin , Cai Mingzhi , Deng Jingyu , Wu Liangliang , Huang Wenbai , Liu Hongmin , Sun Yan , Liang Han 
Published: June 2021

e16041 Background: Chemotherapy and PD-1 inhibitor have shown significant clinical benefits in first-line treatment of GC, overall survival was still dismal. The surgical intervention with curative or life prolonging intention was evaluated as feasible for stage IV GC from clinical trials and retrospective cohorts. Our previous study of cytotoxic chemotherapy (S-1 & PTX) in combination with multi-targets anti-angiogenic TKIs illustrated increased response and R0 resection rate. Given the enhanced response from chemo, PD-1 and TKIs regimens, this trial was designed to assess the feasibility of surgical conversion from this combination in stage IV GC. Methods: This is a prospective, single-arm, single-center, phase II trial. Eligible criteria were treatment naïve, histopathologically confirmed stage IV (AJCC8th) and ECOG PS 0-1 GC adenocarcinoma. Pts were given with sintilimab (200mg, iv, d1) combined with Nab-PTX (w/o peritoneal spread: 260 mg/m2, iv, d1; w/ peritoneal spread: 180 mg/m2, iv, d1 and 80 mg/m2, ip, d1), S-1 (60mg, po, bid, d1-14), and apatinib (250mg, po, qd) every 3 wks. Tumor response was assessed every 2-4 cycles by radiologic imaging and MDT was employed to determine surgical feasibility. Safety run-in was employed in the first 3+3 pts by DLTs to determine the tolerability. The primary endpoint was ORR and R0 surgical conversion rate. Results: 42 pts were enrolled up to 2/2021. The median follow-up was 3.5m (range 0.7-11.3). The median age was 56 yrs (range 31-72), male was 47.6%, and PS 1 was 31.0%. The metastatic factors were characterized as No.16 lymph nodes 54.8% (23), liver 23.8% (10), peritoneum 40.5% (17), Krukenberg 2.4% (1), and extensive metastases (≥2 organs) 42.9% (18). No DLT occurred in initial 6 pts. Of 36 evaluable pts, ORR was 61.1% and DCR was 97.2%. Surgical conversion was currently identified in 18 pts with 94.4% (17) R0 resection, and the R0 surgical conversion rate was 47.2% (17/36). Median treatment cycle in converted pts was 4. 22.2% (4/18) pts achieved pathological complete response (TRG 0), and 27.8% (5/18) pts had major response (TRG 0-1). The most common AEs were grade 1-2, and 1 SAE of hemorrhage grade 4 occurred. No increase of anastomotic leakage, hemorrhage, and abdominal infection, and no surgery caused death and complication caused second operation occurred. The median postoperative length of stay was 9.5d (range 6-16). Conclusions: These preliminary results showed favorable tumor response and acceptable tolerability for potential surgical resection. Sintilimab, doublet chemotherapy, and apatinib might offer an opportunity of cure for stage IV gastric cancer. Trial ID: NCT04267549. Clinical trial information: NCT04267549. [Table: see text]