bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bevacizumab associated calcifications might be a prognostic marker in patients with metastatic colorectal cancer.
Authors: Zhou Yuwen , Meng Qiu 
Published: May 2020

e16108 Background: Cetuximab associated calcifications is a positive predictive factor in metastatic colorectal cancer (mCRC). In patients with glioblastoma, bevacizumab-induced calcifications are also related to a better prognosis. However, tumor calcifications are rarely recognized in mCRC patients treated with bevacizumab. This study was to investigate the correlation between clinical outcome and calcification in mCRC who received bevacizumab and chemotherapy as the first-line treatment. Methods: A single retrospective cohort study was conducted with all diagnosed mCRC cases who received bevacizumab and chemotherapy as the first-line therapy in our hospital from January 2016 to January 2019. Clinical variables were retrieved from medical records and tumor calcification were evaluated independently by radiologists on the basis of computed tomography scans. A univariate and multivariate COX regression analysis was performed to evaluate the association between calcification and outcome. Results: 159 patients with an average age of 59.0 years were included. Median follow-up was 29.6 months. Among all enrolled patients, 31 had tumor calcification [31/159 (19.5%)]. The median overall survival (OS) and progression-free survival (PFS) was significantly better in patients with calcification than those without calcification (28.0 vs. 24.9 months, p= 0.024; 12.0 vs. 10.0 months, p= 0.026). A higher objective response rate (61.3% vs. 50.0%) was also observed in calcification group. On multivariate analysis, tumor calcification was independently associated with OS (hazard ratio 1.799, 95% CI 1.002–3.230) and PFS (hazard ratio 1.609, 95% CI 1.013–2.557). Conclusions: Tumor calcification was independently associated with improved prognosis in colorectal cancer. It might be a potential prognostic marker.
Do irinotecan (IRI) dose reductions driven by UGT1A1*28 genotyping prevent IRI-related severe neutropenia? A real-world study.
Authors: Personeni Nicola , Mineri Rossana , Michelini Angelica , Bozzarelli Silvia , Pressiani Tiziana , Smiroldo Valeria , Sandri Maria Teresa , Giordano Laura , Santoro Armando , Rimassa Lorenza 
Published: May 2020

e16116 Background: IRI is widely used in the treatment of gastrointestinal cancers. Consistent with current guidelines, UGT1A1 genotyping may drive IRI dose reductions, but the usefulness of this approach is still unclear. We assessed potential clinical variables that may predict grade ≥3 neutropenia and more specifically the upfront genotyping of UGT1A1 polymorphisms associated with IRI toxicity, according to predefined IRI dose reductions. Methods: We genotyped UGT1A1*28 polymorphisms in 247 patients with metastic colorectal, gastric and pancreatic cancers who received second or third-line IRI-based chemotherapy in clinical practice at a single academic center. Concomitant DPYD sequencing was undertaken in 179 patients receiving also fluoropyrimidines. We compared the incidence of severe neutropenia with full-dose IRI in UGT1A1 6/6 and 6/7 carriers, and in UGT1A1 7/7 carriers who underwent initial IRI dose reductions by at least 30%. Results: The incidence of UGT1A1 7/7, 6/7, 6/6 genotypes was 11.3%, 51.4%, and 37.2%, respectively. IRI dose reductions were significantly more frequent with UGT1A 7/7 and 6/7 genotypes (odds ratio [OR] = 9.5; 95% confidence interval [CI]: 4.3-21.7), and combination chemotherapy (OR = 3.8; 95%CI: 1.3 – 11.1). Other clinical parameters, including sex, cancer type, baseline neutrophils levels, performance status were not significantly associated with IRI dose reductions. Despite initial IRI reductions driven by the UGT1A1 panel, patients with UGT1A1 7/7 genotype had an increased, albeit non-significant, risk of grade ≥3 neutropenia, compared to patients with UGT1A1 6/6 and 6/7 genotypes who received full dose IRI (incidence: 39% versus 21%; OR = 2.4; 95%CI: 0.85 – 7.03). Conclusions: UGT1A1 testing is a determinant of IRI dose reductions, however this strategy does not reduce the burden of grade ≥3 neutropenia in UGT1A1 7/7 carriers. Further studies beyond the UGT1A1*28 genotype are needed to fully understand the increased risk of neutropenia in patients candidate to IRI-based chemotherapy.
Alterations of DNA damage repair genes in Chinese colorectal cancer patients.
Authors: Li Wenliang , Zhu Zhu , Xu Ning , Huang Wei , Shi Junping , Shi Jiaochun , Wang Weifeng , Klempner Samuel J , Zhao Juan , Gan Jialiang 
Published: May 2020

e16121 Background: Colorectal cancer (CRC) is the second most common cancer in women and third in men. DNA damage repair (DDR) deficiency has emerged as a predictive biomarker for chemotherapy, PARP and immune checkpoint inhibitors. However, comprehensive molecular characteristics of DDR variants in Chinese CRC patients is lacking. Methods: Formalin fixed, paraffin embedded (FFPE) tumor tissues and matched blood samples were collected for targeted next-generation sequencing (NGS) assay. The testing was carried out in a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Alterations of six functional gene sets involved in DDR pathways: homologous recombination (HR), mismatch repair (MMR), base excision repair (BER), nonhomologous end-joining (NHEJ), checkpoint factors (CPF) and Fanconi anemia (FA) were analyzed. The association of DDR gene mutations with TMB/MSI was assessed. Results: In total, 319 CRC patients were recruited, 127 female and 192 male with a median age of 59 (range 23-92). Over one third (36%,115/319) patients had at least one mutation in DDR genes. Mutation rates varied in different DDR pathway: HR (20.7%), CPF (15.1%), FA (11.3%), MMR (10.3%), BER (8.8%), and NHEJ (5.3%). The most frequently mutated DDR genes were ARID1A (13.4%), ATM (10.2%), BRCA2 (6.8%), MLH1 (5.6%), MSH6 (5.6%), POLE (5.0%). Germline mutations in MLH1 (2.5%), BRCA2 (1.2%), MSH2 (0.9%), MSH6 (0.9%), FANCA (0.9%), ATM (0.6%), BRCA1 (0.3%), and CHEK2 (0.3%) were detected in 24 patients. DDR variations were enriched in the right-side CRC compared to the left side CRC (50% vs. 32.8%, p= 0.024). Early stage (I-II) harbored more DDR variations. 20.1% of patients had high TMB (≥10 muts/Mb) with a median of 51 muts/Mb (10-326.7 mus/Mb). Patients with DDR mutations had a significantly higher TMB than patients with wild type DDR (8.5 vs. 4.6 muts/Mb, p< 0.001). All CRC tumors with high MSI harbored DDR mutations. Importantly, the mutations in “HM” (HR/MMR), but not BER/CPF/NHEJ/FA mutations, were significantly correlated with high MSI ( p< 0.001). Conclusions: DDR gene alterations occurred in 36% of Chinese CRC patients and were enriched in right sided tumors. DDR pathway alterations are relatively frequent in CRC and consideration for biomarker-enriched clinical trials with PARP, immune checkpoint inhibitors, and novel combinations are warranted.
Real-world outcomes for neoadjuvant capecitabine versus infusional 5-fluorouracil in the treatment of locally advanced rectal cancer.
Authors: Loft Matthew , Wong Hui-Li , Kosmider Suzanne , Lee Margaret , Tie Jeanne , Wong Rachel , Jones Ian , Croxford Matthew , Steel Malcolm , Faragher Ian , Guerrieri Mario , Christie Michael , Gibbs Peter 
Published: May 2020

e16124 Background: Neoadjuvant chemoradiation therapy (CRT) is a standard of care treatment for locally advanced rectal cancer (LARC). A pathologic complete response (pCR) following CRT is an early indicator of treatment benefit and associated with excellent survival outcomes. As capecitabine replaces infusional 5-fluorouracil (5-FU) as the fluoropyrimidine of choice in routine care of LARC, on the back of clinical trial data demonstrating equivalence, it is important to confirm that efficacy is maintained in the real-world setting. Methods: We analysed data from a prospectively maintained colorectal cancer database at 3 Australian hospitals including patients diagnosed January 2009 to December 2018. Pathological response was determined as either complete or incomplete and compared for patients receiving 5FU or capecitabine. Results: 657 patients were analysed, 498 receiving infusional 5-FU and 159 capecitabine. Capecitabine use has markedly increased from approval in 2014, now being used in more than 80% of patients. Patient characteristics were similar by treatment, including age, tumour location and pre-treatment stage. pCR was reported in 22/159 (13.8%) of capecitabine treated patients and 118/380 (23.7%) that received 5-FU (p = < 0.01). More capecitabine-treated patients received post-operative oxaliplatin (44.2% vs 6.3%, p < 0.01). Two-year progression free survival was similar (84.9% vs 88.0%, p = 0.34). Conclusions: Capecitabine is now the dominantly used neoadjuvant chemotherapy in LARC. Capecitabine use was associated with a lower rate of pCR versus infusional 5FU, a difference not explained by examined patient or tumour characteristics. Poor treatment compliance with an oral therapy in the real-world setting is one possible explanation.
First-in-human (FIH) phase I study of GST-HG161, a potent and highly selective c-met inhibitor, in patients with advanced solid tumor.
Authors: Li Jin , Guo Ye , Xue Junli , Wu Wenqiang , Chen Shikui , Tang Yanan , Xu Xiongbin , Li Gang , Hu Lihong , Lin Yunfei , Shen Liang , Xia Yuanfeng , Chan Chi-Chung , Wang Zhouchong , Ni Dawen , Ding Charles , Chen Shuhui 
Published: May 2020

e16126 Background: GST-HG161 is an orally bioavailable novel potent and highly selective c-Met inhibitor, which displayed significant antitumor activity in preclinical models as well as very desirable pharmaceutical properties for oral dosing. Preclinical studies demonstrated that GST-HG161 has the potential to be effective in HCC patients with active c-Met signaling. Methods: This is an open label, first-in-human, single center, dose-escalation study (NCT04228406) utilizing an accelerated dose escalation design using single patient cohorts for the first two dose levels (60 and 150 mg) followed by a conventional 3+3 design at the 3rd dose cohort (300 mg). Dose escalation is expected to continue to the proposed 7th dose cohort (900 mg). The objective of the study is to determine the maximum tolerated dose and/or recommended Phase II dose, dose limiting toxicities (DLT), safety, pharmacokinetics, pharmacodynamics and preliminary signals of anticancer efficacy of GST-HG161 in patients with advanced solid tumors. Eligible patients are adults with advanced solid tumors refractory to standard therapies with confirmed c-Met positive. The definition of c-Met positive is a) IHC expression of c-Met (positive criteria: 1+ and above) and/or b) FISH amplification of c-Met and/or c) MET exon 14 (METex14) skipping. GST-HG161 is administered orally once-a-day starting on day 1 of each 21 days cycle. Results: To date, 6 patients (CRC 2, Gastric 1, NSCLC 1, HCC 1, Cholangiocarcinoma 1) were enrolled to 3 dose levels (60, 150, and 300 mg). Of these 6 patients, 4 had discontinued GST-HG161 treatment at the data cut-off date of Feb 1, 2020, due to progressive disease (3) and adverse event (1). Two patients at the 300 mg cohort are still on treatment. Overall, 4/6 patients showed no drug-related AEs > Grade 1. One patient reported a DLT: asymptomatic Grade 3 lipase elevation after a single dose of 60mg. To date, no other patients showed elevations of lipase and amylase. Bioanalysis of PK samples from study patients are currently ongoing. PK summary will be reported in the presentation. Conclusions: GST-HG161 has been well tolerated to date in study patients with a manageable safety profile. The dose escalation is expected to continue to the proposed 7th cohort at 900 mg. Clinical trial information: NCT04228406 .
Induction chemotherapy with mFOLFOXIRI in cT4N+ locally advanced rectal cancer: Subgroup analysis from a prospective trial.
Authors: Zhang Jianwei , Hu Huabin , Cai Yue , Xie Xiaoyu , Wu Zehua , Ling Jiayu , Deng Yanhong 
Published: May 2020

e16136 Background: FOLFOXIRI had been recommended as induction treatment for patients with T4N+ rectal cancer in the latest NCCN guideline. However, no prospective study to support this recommendation in his population. Here, we tried to analyze the efficacy of FOLFOXIRI as induction chemotherapy in the subgroup of rectal cancer patients with T4N+ from a prospective trial. Methods: A phase II trial exploring the efficacy of mFOLFOXIRI as neoadjuvant chemotherapy in locally advanced rectal cancer had been conducted in our center recently. The subgroups of patients with clinical T4N+ rectal cancer were extracted for further analysis. All candidates were to receive 4 to 6 cycles of mFOLFOXIRI. MRI will be performed every two cycles to assess clinical responses. And then the patients would receive total mesorectal excision directly or proceed to chemoradiotherapy according to the result of restaging evaluation. Postoperative FOLFOX chemotherapy was recommended. The primary endpoint is the ratio of tumor downstaging to ypT0-2N0M0. Results: There were 27 patients with cT4N+. There were twenty male and 7 female, with the median age of 46 years old. MRF involved was observed in 14 patients. Neoadjuvant chemotherapy with mFOLFOXIRI was performed for at least 4 cycles. Six patients received radiotherapy before total mesorectal excision, including short-term radiation in 1 patient. R0 resection was achieved in all the patients (100%) and 24 (88.9%) of patients had received sphincter-saving operation. According to the pathologic result, all patients showed regression in the primary tumor (ypT0-3). The pCR rate was 22.2% (6/27) and the tumor downstaging (ypStage 0-I) rate was 29.6%. Another 13 (48.1%) patients showed downstaging to ypStage II. The main grade 3/4 adverse event was neutropenia (35.7%). With a median follow-up of 25 months, no local recurrence was observed. Only 3 patients developed distant metastasis. The 2-year survival rate for this group of population was 85.0%. Conclusions: mFOLFOXIRI showed high tumor downstaging rate in locally advanced rectal cancer. It could be reasonable to use mFOLFOXIRI as induction chemotherapy for cT4N+ rectal cancer patients. Clinical trial information: NCT02217020 . [Table: see text]
Clinicopathologic features and survival outcomes of signet cell carcinoma of the appendix: Analysis of the SEER database.
Authors: Abushalha Kamelah , Tuqan Wa'el , Albagoush Sara , Abulaimoun Sawsan , Silberstein Peter T. 
Published: May 2020

e16147 Background: Signet ring cell carcinoma of the appendix (SRCCA) is an exceedingly rare tumor, and limited data are available on the characteristics and survival probabilities of this tumor. Methods: Surveillance, Epidemiology, and End Results (SEER) database was used to identify 527 patients diagnosed with SRCCA between 2000 and 2015. The database was used to examine demographic information. Survival analysis was made by Kaplan-Meier and compared by log-rank test. Cox proportional hazards model was adopted for prognostic variable evaluation. Results: The majority of SRCCA patients were female (63.9%) and white (83.8%), with a mean age at diagnosis of 56 years. Histologically; 60% of the tumors were of high grade (poorly-differentiated and undifferentiated). The majority of patients were diagnosed with metastatic disease (61.3%) and received surgical treatment (86.5%), with sub-total colectomy was the most common surgery performed (45.6%). Median overall survival was 26 months, with a cancer-specific survival at three-year and five-years of 39% and 18.4%, respectively. There was a 10-year difference in median survival time based on sex (females vs males; 23 vs 33 months respectively). On bivariate analysis; factors associated with significantly increased mortality (p < 0.05), include increased age (HR 1.02), female gender (HR 1.33), AJCC T category (T4 compared to T0; HR 1.96), AJCC N category (N1 compared to N0; HR 1.9) and AJCC M category (M1 compared to M0: HR 2.62). Factors associated with improved survival (p < 0.05) included treatment by surgical resection; total colectomy (HR 0.47) and sub-total colectomy (HR 0.45) . Conclusions: This is the largest study to date on SRCCA. Older white females are most commonly affected and often diagnosed at advanced stage and grade.
Outcome of locally advanced carcinoma of oesophagus: A single institution experience.
Authors: S Thianeshwaran , Bj Sriniivas , Sanghavi Niyati Prakash , Sarathy Vinu , Lalkota Bhanu Prakash , PK Kiran , Byas Nitin , Shah Mansi , N Madhusudhan , Varayathu Hrishi , Puii Lalnun , Hazarika Diganta , Mufti Suhail Sayeed , Ajaikumar Basavalinga Sadasivaiah , Radheshyam Naik 
Published: May 2020

e16507 Background: Oesophageal cancer is the twelfth most common cancer worldwide and seventh leading cause of cancer related death. Neoadjuvant treatment in addition to surgery has shown improved overall survival compared to surgery alone in resectable oesophageal cancer. We aimed to analyse the survival outcome among locally advanced oesophageal carcinoma patients in neoadjuvant setting. Methods: We analysed 37 patients with locally advanced carcinoma of oesophagus from 2015 to 2019 who underwent neoadjuvant chemoradiotherapy followed by surgical excision of tumour. Descriptive analysis was used for demographic data. overall survival and disease free survival was analysed using Kaplan-Meier survival analysis. Results: Our study includes 20 males (54%) and 17 females (45%). Over all consumption of Tobacco and alcohol consumption was found to be 64% and 18% respectively. The most common tumour site in this study was middle oesophagus (56%) followed by lower (37%) and upper (5%). Histopathologically, moderately differentiated squamous cell carcinoma constituted the highest (62%), followed by well differentiated squamous cell carcinoma (21%) and poorly differentiated carcinoma (16%). The pathological stage post chemoradiotherapy was 80%, 50% and 57% for stage I, II and III respectively. Median over all survival is 60 months and no statistical difference in stage I and stage II. Median over all survival for poorly differentiated squamous cell carcinoma is 16 months and lower one third of squamous cell carcinoma is 37 months. Complete pathological response is 42 %. Conclusions: Our study concluded that patients with tobacco and alcohol consumption have poorer survival. Prognosis was worst for patients with lower end oesophagus and poorly differentiated type. Disease free survival was better for patients who achieved complete pathological response when compared to partial responders.
Effects of removing heat and phlegm prescription on the proliferation and autoantigens expression of esophageal carcinoma cell.
Authors: Si Fuchun 
Published: May 2020

e16510 Background: o explore the effects of removing heat and phlegm prescription (RHPP) on the proliferation and autoantigens expression of esophageal carcinoma(EC) cell, so as to provide basis for the molecular pathogenesis and clinical medication of EC. Methods: RHPP was developed by us for treating EC, EC autoantigens CK13, CK16, CaD, ACTG2 were identified in our previous studies. The effects of RHPP and and its ethanol extraction on the proliferation, cell cycle and autoantigen protein expression of Eca109 cell, EC9706 cell and TE-1 cell were investigated by MTT assay, flow cytometry and western blot analysis. Results: RHPP and its removing heat (RH) and removing phlegm (RP) separated prescriptions all have inhibitory effects on the proliferation of EC9706, EC109 and TE-1 cells in dose-dependent and time-dependent manner, changed morphology of four esophageal carcinoma cells, which appeared as round with rough edges, karyopyknosis, and karyorrhexis. Ic50 values of RHPP for Ec9706, Eca109 and TE1 cell were 33.31 ug·ml−1, 20.70 ug·ml−1, 21.93 ug·ml−1 respectively, while Ic50 values of RHPP’s ethanol extraction for Ec9706, Eca109, TE1 were 0.653 ug·ml−1, 0.082 ug·ml−1, 0.172 ug·ml−1 respectively. RHPP and RP induced G2/M phase arrest in EC109 and TE-1 cells, while RH induced G0/G1 phase arrest in EC109 and TE-1 cells; RHPP and RP induced G0/G1 phase arrest in EC9706 cells, while RH induced S phase arrest in EC9706 cells. RHPP and its two separated prescription could downregulate CK16, CaD, ACTG2 expression and upregulate CK13 expression. Conclusions: Autoantigens CK13, CK16, CaD and ACTG2 were expressed in EC cell, RHPP could regulate these four autoantigens expression. This study provides new basis for the EC mlecular mechanism and development of anti-esophageal carcinoma drugs in traditional Chinese medicine.
Observation on the clinical effect and survival period of patients with esophageal cancer treated with UMIPIC combined with low dose radiotherapy.
Authors: Liu Jian , Jing Peng , Gao Feng , Shang Wei , Zhang Peicheng , Zhang Xiaomin , Feng Jianbin , He Guangyong , Zhang Gequn , Li Wenli , Wu Yanfei , Yu Baofa 
Published: May 2020

e16517 Background: To observe the clinical effect and survival period of UMIPIC (ultra-minimum incision personalized intratuoral chemoimmunotherapy) combined with radiotherapy in the treatment of esophageal cancer. Methods: 712 patients with esophageal cancer who received UMIPIC treatment in our hospital from January 2011 to December 2015 were selected for the study subjects, 540 cases were treated by UMIPIC combination with radiotherapy in group A and 172 cases were treated by UMIPIC without radiotherapy in group B. All patients were diagnosed with esophageal cancer, and signed the consent for treatment. The patients were treated according to the UMIPIC treatment guidelines. This study was to observe the adverse reactions, clinical efficacy, survival and survival rate of esophageal cancer patients treated with UMIPIC combined with low-dose radiotherapy. Results: The common adverse reactions in group A were fever (18.06%), pain (8.89%), hemoglobin reduction (5.59%), leucopenia (5.40%), nausea (1.48%) and thrombocytopenia (1.12%);The common adverse reactions in group B were fever (26.16%), hemoglobin reduction (17.16%), pain (16.86%), leucopenia (3.55%), thrombocytopenia (2.35%), nausea (1.74%), liver function damage (2.42%), renal function damage (1.21%) and vomiting (1.16%). The other adverse reactions were all lower than 1.00%; The fever, pain and hemoglobin decrease in group A were significantly lower than those in group B (P < 0.05). There were 522 patients whose clinical efficacy could be evaluated in 712 patients. The benefit rate of group A was 95.28%, higher than that of group B 91.84%.The mean and median survival time of group A was 28.412 and 15.670 months, significantly higher than that of group B at 22.103 and 7.070 months. The 1-year survival rate of group A was significantly higher than that of group B (P < 0.05). The 1-year, 2-year and 5-year survival rates of group A were 60.05%, 35.61% and 28.26% while the 1-year, 2-year and 5-year survival rates of group B were 36.94%, 26.44% and 25.00%. Conclusions: The main adverse reactions of UMIPIC in the treatment of esophageal cancer are fever and pain, and other adverse reactions are relatively low. Combined radiotherapy can improve the clinical benefit rate, prolong the survival time and the clinical treatment effect is good, it is encouraged to treat esophageal cancer using local therapy of UMPIC with radiotherapy at low dose.