bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of NTRK1/3 fusions in mismatch repair-deficient (dMMR)/microsatellite instable (MSI) tumors of patients with metastatic colorectal cancer (mCRC).
Authors: Svrcek Magali , Colle Raphael , Cayre Anne , Bourgoin Pierre , Cohen Romain , Andre Thierry , Penault-Llorca Frederique Madeleine , Radosevic-Robin Nina 
Published: June 2021

e15537 Background: Inhibitors of tropomyosin receptor kinase (TRK) have shown promising activity against neurotrophic TRK ( NTRK) fusion-driven cancers, regardless of tumor histotype or cell of origin. NTRK gene fusions are observed in less than 1% of colorectal cancers (CRCs). CRCs harboring wild-type BRAF and KRAS and MisMatch Repair deficiency (dMMR)/MicroSatellite Instability (MSI) due to MLH1 hypermethylation have been associated with NTRK fusions in small cohorts of non-metastatic tumors. We aimed at evaluating the incidence of NTRK fusions among dMMR/MSI metastatic CRCs (mCRC) for which there is a need for innovative therapies, as well as the associated clinical characteristics of these patients (pts) carrying NTRK fusion-positive tumors. Methods: Tumor samples of dMMR/MSI mCRC pts, paired primary and metastasis or primary alone, were obtained from a French multicenter retrospective cohort and from a single-center cohort of patients treated by immune checkpoint inhibitors (ICI) (Saint-Antoine Hospital, Paris). Clinico-pathological data including KRAS and BRAFV600E status, MMR proteins and MLH1 methylation status were available for all pts. All samples were screened for TRK expression by immunohistochemistry (IHC) using a pan-TRK antibody (clone EPR17341, Abcam; positivity: 1% of labeled tumor cells)) and for NTRK1 and NTRK3 gene rearrangements, by fluorescent in situ hybridation (FISH). A threshold of 15% nuclei positive for a break apart signal was considered positive for gene rearrangement. Results: A total of 158 pts with dMMR/MSI mCRCs (paired samples: n=39; primary only: n=119) were screened. Tumor samples of 10 patients (6.3%) harbored NTRK fusion genes by FISH ( NTRK1=8; NTRK3=2). Only four of these 10 patients had TRK immunoreactivity. One patient showed a discordance between metastasis harboring NTRK1 fusion (+) and primary tumor being negative. Eight tumors were sporadic with MLH1 hypermethylation. The remaining 2 cases were related to a MMR gene germline mutation (Lynch syndrome) with concurrent loss of MSH2 and MSH6 expression and isolated loss of MSH6 respectively. One Lynch-related tumor was KRAS mutated, one sporadic MLH1-negative tumor was BRAF V600E mutated. Four patients out of 91 treated by ICI had tumors with NTRK fusions. Three have shown radiological response according to iRECIST criteria (two complete responses, one partial response with 25 to 54 months of follow up) and one had primary resistance to ICI. Conclusions: Frequency of NTRK1/3 fusions is 6.3% in our dMMR/MSI mCRCs population. These fusions are not restricted to sporadic cases. The diagnostic accuracy of pan-TRK IHC is low. Optimal testing algorithms for theragnostics remain to be defined in this setting.
Effectiveness and tolerability of FOLFOXIRI regimen in the third- and subsequent lines of therapy in patients with metastatic colorectal cancer.
Authors: Yakimovich Kseniya , Alaniya Mariya , Shilo Polina , Mochalova Anastasia , Ledin Evgeny 
Published: June 2021

e15584 Background: Options of therapy are limited for patients with colorectal cancer who developed disease progression during standard 5-FU-, oxaliplatin-, and irinotecan-contained regimens. There is straight information about synergy of irinotecan (SN-38) and oxaliplatin gained from fundamental and early clinical trials. We aimed to analyze effectiveness and safety of triple drug-combination of 5-FU, oxaliplatin and irinotecan (FOLFOXIRI) in heavily pretreated patients with metastatic colorectal cancer. Methods: Patients with a metastatic colorectal cancer who received more than 2 lines of standard 5-FU-, oxaliplatin- and irinotecan-based doublet regimens with or without targeted therapy were included. Reinduction of chemotherapy in previous lines was allowed. The retrospective analysis of medical histories was done. Eligible patients had to receive number of cycles that were sufficient for response rate estimation. Disease response was evaluated according to RECIST 1.1 criteria. Survival analysis was performed using the Kaplan-Meier method. Tolerability was estimated by CTCAE v. 5.0. Results: Forty-six patients were included in retrospective per protocol analysis. The median follow-up was 19 months. The median number of previous lines of chemotherapy was 2 (2-6). Primary resistance to oxaliplatin- and irinotecan-based chemo during previous lines was noted in 20 patients (43%) and 16 patients (35%), respectively, while seven patients (15%) developed the primary resistance to both agents given in a sequential order. All patients were treated with targeted therapy during previous treatment lines. The median of FOLFOXIRI cycles was 8 (range, 2-19). Two patients (4%) were treated with FOLFOXIRI without any targeted agents. The objective response rate was 33% (n = 15). The disease stabilization was reached in 43% (n = 20). The disease control rate was 76% (n = 35). Eleven patients (24%) had the progression of disease at the first follow-up. The median progression free survival and median overall survival were 6 months and 11 months, respectively. Toxicity was evaluated in 35 patients. The most common severe adverse events (grade 3 and 4) were neutropenia (46%) and fatigue (26%). Treatment was delayed in 20 patients (57%), and 13 patients (37%) required dose reduction. One patient had to discontinue treatment due to unacceptable toxicity. Conclusions: According to our study FOLFOXIRI provides the objective response and increased life expectancy in heavily pretreated patients. The further assessment of FOLFOXIRI regimen for refractory colorectal cancer in the prospective trials is needed.
Neoadjuvant chemotherapy for locally advanced colon cancer patients: Long-term results from a single institutional experience.
Authors: Ceniceros Lucia , Pastor Carlos , Sanchez-Justicia Carlos , Arean Carolina , Baixauli Jorge , Chopitea Ana , Granero Lucia , Arredondo Jorge , Martinez Patricia , Hernandez-Lizoain Jose Luis , Rodriguez Javier 
Published: June 2021

e15598 Background: Neoadjuvant chemotherapy (NAC) is an emerging alternative in the management of patients with locally advanced colorectal cancer (LACRC), with promising results in terms of R0 resection rates, compliance, postoperative morbidity and a trend towards reduced risk of relapse. However, more mature data are required. We evaluated the long-term outcome of this strategy in our institution. Methods: We retrospectively analysed LACRC patients treated preoperatively with either biweekly FOLFOX or XELOX at standard doses as a follow-up of our previous experience with this neoadjuvant approach. Patients were identified from a prospectively collected tumor registry database from our institution. Clinical staging was based on colonoscopy and CT-scan. Only patients with radiological signs of lymph node involvement and/or extramural invasion > 5 mm were included. The uracil/dihidrouracil ratio was calculated at baseline as a surrogate marker of DPD deficiency. Pathological tumor regression was graded according to the MSKCC and toxicity with the NCI-CTCAE 4.0. Results: From February 2006 to November 2019 91 pts with MSS LACRC (M/F: 62/29; median age 66. Clinical stage; T3: 60.4%, T4: 37.4%, N+: 75.8%; Sideness: 82.4% left located were analysed. Preoperative chemo was FOLFOX in 46 pts and CAPOX in 45 pts. Median number of preoperative cycles was 4 (range 1-10). Side effects profile included G3-4 diarrhea (3.3%), G2 sensitive neuropathy (12.1%) and G2 neutropenia (4.4%). 9 pts had a treatment delay due to haematological toxicity. No progressive disease was noted during neoadjuvant chemotherapy. All patients underwent surgery, most of them (63.7%) by a laparoscopic approach. pCR was found in 11 pts (12.1%). Grade 3, 3+ and 4 tumor regression according to MSKCC score was reached in 50.5% of the patients (Median number of harvested nodes was 17 (range 7-51), with 75.8% being ypN0. Lymphovascular and perineural invasion were found in 7.7% and 6.6% of the patients, respectively. The median hospital stay was 7 days (3-36) and 13 pts develop any surgical complication. 37.4% received adjuvant treatment. After a median follow-up of 63 months, median progression-free (PFS) and overall survival (OS) have not been reached. 5-year actuarial PFS for right and left LACRC was 77 and 87%, respectively. Conclusions: Our data add to the growing evidence suggesting that NAC may play a meaningful role in LACRC patients
Effects of prognostic nutrition index on side effects and prognosis of radiotherapy and chemotherapy after radical gastrectomy.
Authors: Liu Jiyu , Dong Hongmin , Wang Wenling , Wang Gang , Pan Huan , Chen Weiwei , Wang Qian , Wang Ze-Jun 
Published: June 2021

e16002 Background: To investigate the impact of preoperative prognostic nutritional index (PNI) on the severity of radiotherapy and chemotherapy toxicity and survival prognosis in patients with gastric cancer through retrospective analysis and research in order to guide clinical nutritional support treatment for patients with gastric cancer. Methods: Through a retrospective cohort study，we analyzed the data of 191 patients with gastric cancer in the Department of Gastrointestinal Surgery of the Affiliated Hospital of Guizhou Medical University and Guizhou Cancer Hospital from January 2008 to December 2018. According to the cut-off value, the patients were divided into high PNI group (PNI≥47.7) and low PNI group (PNI < 47.7). We Compared the incidences of severe radiotherapy and chemotherapy toxicities and overall survival in high PNI group and low PNI group. and make Analysis of prognostic factors. Results: The low PNI group was more prone to severe radiochemotherapy hematological side effects than the high PNI group, and the postoperative survival time was shorter. Multivariate analysis showed that: TNM stage (P = 0.000) and PNI (P = 0.001) were Independent risk factors in predicting overall survival rate. Conclusions: The preoperative prognostic nutrition index is a useful factor for predicting the incidence of radiotherapy and chemotherapy toxicities in patients after gastric cancer surgery.It is one of the important factors affecting the prognosis of gastric cancer and helps to guide the nutritional support treatment of gastric cancer patients.
A real-world clinical study of camrelizumab in the treatment of esophageal cancer.
Authors: Sun Guoping , Qian Dong , Zhao Dong , Liang Hui , Cheng Huaidong , Wang Genhe , Wang Fan , Jiang Hao , Xu Tengyun , Wu Qibing , Zhu ShaoJin , Xu Dong 
Published: June 2021

e16008 Background: Camrelizumab, a fully humanized monoclonal antibody against PD-1, has been approved in the treatment of advanced esophageal squamous carcinoma in China. The purpose of this study was to observe the efficacy and safety of Camrelizumab in the treatment of esophageal cancer in the real world. Methods: This is an open-label, prospective, multicenter, observational study. Eligible patients (pts) who received Camrelizumab had esophageal cancer; age≥18, ECOG PS of 0-2; and measurable disease. Results: As of November 30, 2020, a total of 229 patients were enrolled, of which 192 were male (83.8%). The ECOG PS score was 0 in 48 cases (21.0%), 1 in 149 cases (65.0%), and 2 in 32 cases (14.0%). Among the 134 patients of stage IV patients (58.5%), 174 patients had metastases (76.0%), and 99% of patients did not undergo PD-L1 testing. A history of radiotherapy accounted for 57.6%, and a history of surgery on the primary lesion accounted for 42%. Camrelizumab accounted for 26.2% of the first-line treatment, 33.6% of the second-line treatment, and 35.4% of the third-line and above. Camrelizumab combined with chemotherapy accounted for 40%, combined with anti-angiogenesis therapy accounted for 38.0%, combined with anti-angiogenesis + chemotherapy accounted for 9.0%, and combined radiotherapy accounted for 6.2%. Among 145 patients with evaluable efficacy, 5 cases of CR, 14 cases of PR, 97 cases of SD, and 29 cases of PD. The ORR reached 13.1% and the DCR reached 80.0%. The overall adverse event rate was 42.8%, the major adverse event RCCEP rate was 11.7%, pneumonia was 8.3%, and fatigue was 4.1%. Adverse events greater than or equal to grade 3 included 1 case of RCCEP, 3 cases of bleeding, 1 case of diarrhea, and 1 case of fever. Conclusions: In this real-world study of esophageal cancer, most of the patients enrolled were patients with poor PS score and late stage, but the efficacy and safety of Camrelizumab in patients with advanced esophageal cancer were still confirmed. The dominant population and combination therapy are still under study. Clinical trial information: ChiCTR1900027275.
Camrelizumab in combination with preoperative chemotherapy for locally advanced esophageal squamous cell carcinoma: A single-arm, open-label, phase II study.
Authors: Wang Feng , Qi Yu , Meng Xiangrui , Fan Qingxia 
Published: June 2021

e16072 Background: At present, ESCC has a dismal prognosis with huge unmet clinical needs. With the potential benefit of combining PD-1 inhibitor with nCT, we conducted a phase II trial to assess the efficacy and safety of Camrelizumab plus nCT for locally advanced ESCC. Methods: 43 patients (pts) with histologically confirmed stage II/III/IVa(cT2-4aN0-3M0) ESCC were enrolled from February 2020 to February 2021.The study was divided into two stages, stage 1: we administered 1 cycle of camrelizumab for induction therapy (200 mg q2 weeks); stage2: pts received 2 cycle of camrelizumab (200 mg every 3 weeks) plus docetaxel and nedaplatin, followed by surgery within 4̃6 weeks after neoadjuvant therapy completion. Primary endpoint was major pathologic response (MPR). Secondary endpoints included pathologic complete response (pCR), R0 resection rate, disease-free survival (DFS) and overall survival (OS). Results: At the cutoff date of Feb 5, 2021, 43 eligible pts were enrolled (63% males, median age 66), neoadjuvant treatment was completed in 33 pts and is ongoing in 3 pts. Thus far 27 out of 33 pts were resected, 6 pts are planned to undergo surgery, 3 pts were not suitable for operation after evaluation,1 pt had interval metastases preoperatively, 1 pt declined surgery, 1 pt was allergic to camrelizumab, 1 pt died due to unknown reasons. All patients underwent an R0 resection. Postoperative pathology showed that TNM stage decreased in 23 pts with 85.19% reduction rate. 17 pts (62.96%) reached major pathologic response, 8 pts (29.63%) reached pathologic complete response (no surgery related mortality). The most common AEs (all grade, grade≥3) were reduced hemoglobin (53%, 0%), hypoproteinemia (26%, 0%), neutrophil (21%, 12%), TSH reduction (21%, 0%), increased blood lactate dehydrogenase (16%, 0%), hyperthyroidism (16%, 0%), elevated alanine aminotransferase (9%, 0%), fatigue (7%, 0%), rash (5%, 2%). Date for median DFS and OS were not matured. Conclusions: Camrelizumab in combination with preoperative chemotherapy followed by surgery for locally advanced ESCC showed promising downstaging effect and MPR with good tolerance, and its efficacy and safety could be further studied in later trials. Clinical trial information: NCT03917966. Clinical trial information: NCT03917966.
Analysis of DNA damage response gene signature for prognosis prediction of esophageal squamous cell carcinoma.
Authors: Zhuang Weitao , Ben Xiao-song , Tian Dan , Zhou Zihao , Chen Gang , Deng Cheng , Liao Yuchen , Zhao Jing , Wang Guoqiang , Cai Shangli , Tang Jiming , Shi Ruiqing , Xie Liang , Zhang Dongkun , Zhou Haiyu , Qiao Gui-Bin 
Published: June 2021

e16073 Background: Esophageal squamous cell cancer (ESCC) is a malignant tumor with a poor 5-year relative survival. A prognosis prediction signature associated with DNA Damage Response (DDR) genes in ESCC was explored in this study. Methods: The clinical and gene expression profiles of ESCC patients were downloaded from the GEO and TCGA database. Univariate Cox regression and 1000 iterations of 10-fold cross-validation of LASSO Cox regression with binomial deviance minimization criteria were used to identify DDR genes as potential object and a prognostic signature for ESCC survival prediction, followed by validation of the signature via TCGA cohort and identification of independent prognostic predictors. A nomogram for prognosis prediction was built and Gene Set Enrichment Analysis (GSEA) was performed to further understand the underlying molecular mechanisms. Results: A signature of 8 DDR genes were constructed as being significantly associated with overall survival (OS) among patients with esophageal squamous cell carcinoma. The pronostic signature stratified ESCC patients into low- vs high-risk groups in terms of OS in the training set, testing set and the validation cohorts, and remained as an independent prognostic factor in multivariate analyses (hazard ratio (HR) in training set, 0.17 [95% CI, 0.09-0.35; P < 0 .001], HR in testing set, 0.38 [95% CI, 0.16-0.93; P = 0.029], HR in discovery cohort, 0.171 [95% CI, 0.03-0.48; P < 0 .001]) after adjusting for clinicopathological factors. The 8-DDR gene signature achieved a higher accuracy (C-index, 0.69; AUCs for 1-, 3- and 5-year OS, 0.74, 0.77 and 0.76, respectively) than 7 previously reported multigene signatures (C-index range, 0.53 to 0.60; AUCs range, 0.55to 0.66, 0.54 to 0.64 and 0.62 to 0.66, respectively) for estimation of survival in comparable cohorts. A nomogram incorporating tumor location, grade, adjuvant therapy and signature-based risk group showed better predictive performance for 1- and 3- year survival than for 5 year survival. Moreover, GSEA revealed that the DNA repair was more prominently enriched in the high-risk group while the low-risk group had not enrichment of any process (P > 0.05 for all). Conclusions: Taken together, our study identified 8 DDR genes related to the prognosis of ESCC patients, and constructed a robust prognostic signature to effectively stratify ESCC patients with different survival rates, which may help recognize high-risk patients potentially benefiting from more aggressive treatment.
Income-inequality and rate of doctors per inhabitant and their influence on esophageal cancer mortality in Brazil.
Authors: Schoueri Jean Henri , Werneck De Carvalho Luis Eduardo , Portugal Isabella Batista Martins , de Almeida Roediger Manuela , de Sousa Santos Edige Felipe , Paiva Laercio da Silva , de Abreu Luiz Carlos , Fonseca Fernando Luiz Affonso , Barbosa do Nascimento Vânia , Adami Fernando 
Published: June 2021

e16089 Background: There are substantial disparities in esophageal cancer mortality across different social groups, including sex, race/ethnicity, geographical location and socio-economic status. Methods: This is an ecological study with secondary data from 2016 to 2018 that evaluated the effects of income-inequality and number of doctors per inhabitant on esophageal cancer mortality in Brazil and its Federative Units. The amount of deaths and the overall number of doctors were obtained from the Department of Informatics of the Unified Health System. Mortality was estimated per 100,000 individuals and age-standardized through the World Health Organization’s population, whereas the rate of doctor per inhabitant was calculated per 1,000 inhabitants. Income-Inequality was measured by the Gini index, obtained from the United Nations Development Programme. Linear regression was performed by the stepwise backward method. Results: Sex, Gini index values and oncology surgeons were all related to lower mortality rates (p < 0.05), whereas clinical oncologists and general surgeons were both associated with higher mortality (p < 0.05). Conclusions: Esophageal cancer mortality rates were influenced by both the type and amount of doctors per inhabitant of any given administrative region in Brazil, however there was no association found with regards to income inequality.[Table: see text]
Prolonged overall survival observed in patients with locally advanced gastric cancer receiving prophylactic simplified heated intraperitoneal chemotherapy after D2 surgery.
Authors: Cheng Junchi , Yang Yunshan , Zhong Haijun 
Published: June 2021

e16110 Background: Despite advances in surgery and adjuvant chemotherapy, intraperitoneal recurrence is highly frequent in gastric cancer (GC) with a dismal prognosis. In this retrospective study, we aimed to evaluate the effectiveness of adding simplified prophylactic heated intraperitoneal chemotherapy (sp-HIPEC) between surgery and systemic chemotherapy. Methods: Clinical data of 170 patients diagnosed as having locally advanced GC and receiving D2 surgery were retrospectively reviewed. Of the patients, 99 received sp-HIPEC, followed by systemic postoperative chemotherapy, and 71 received only systemic postoperative chemotherapy. Overall survival and recurrence rates between the groups were compared. Results: The median survival was 30.3 and 17.2 months for the sp-HIPEC and systemic groups, respectively (hazard ratio, 0.56; 95% CI, 0.10-0.97). The 3- and 5-year survival rates were 48.2% vs 41.4% and 22.9% vs 14.4%, respectively. Moreover, adding sp-HIPEC significantly reduced peritoneal relapse rate.Both regimens were well tolerated. Conclusions: Adding sp-HIPEC between surgery and systemic chemotherapy may benefit the overall survival without causing additional treatment toxicity.