bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using deep learning to recognize local advanced rectal cancer in CT images.
Authors: Lin ChunYu 
Published: June 2023

e15624 Background: Colorectal cancer was the most prevalent malignant disease in developed country and cause 45% mortality rate. Rectal cancer accounted 40% of this disease and is difficult to treat due to its anatomical position. Preoperative neoadjuvant radio-chemotherapy for local advanced rectal cancer can increase circumferential resection margin (CRM) which lead to lower local recurrence rate. MRI was suggested as staging methods for CRM status and nodal evaluation. However, MRI resources were much less than CT scans. CT scans was prevalent and can provide substantial agreement in CRM evaluation under experienced specialist. This study tries to use deep learning to detect local advanced rectal cancer in CT images at initiation of treatment as advisement for neoadjuvant chemoradiotherapy. Methods: From 2010.10.1~2021.12.31, rectal cancer patients with cT3-4 lesion was included. Collect high quality CT images with DICOM files in tumor segment. cT1-2, low rectal lesions, non-CRC cases were not included. Non-contrast and artificial defect images were also excluded. CT images were labeled as” diseased “ when CRM were threatened ( < 2mm). All images were labeled according to judgment of 2 specialist. The data were separated into 2 parts. One for AI model training and testing, another for external validation. The training testing dataset was achieved by deep learning neuro network and evaluating model accuracy performance. Then the model was applied into external validation dataset for real-world testing, evaluating coherent rate between AI and the Dr. decision. Furthermore, to see the cancer survival outcomes according to AI model prediction results. Results: From 2010.10.1~2022.12.31, 1256 rectal cancer cases images were included. 706 cases (889 CT series, 5958 images) with cT3-4 lesions and high quality DICOM files were eligible. 620 cases (803 series, 5318 images) with cT3-4 lesions were classified in training validation set. 1907 (35.9%) images were diseased, 3411 (64.1%) images were normal. 86 clinical stage 2-3 cases (640 images) directly underwent resection during 2014.12.1-2017.5.31 were classified as external validation group. For recognizing CRM+ local advanced rectal cancer by EfficientNetB0, the algorithm achieved an area under the receiver operating characteristic curve (AUC): 0.91 (86.1% accuracy). For External validation set, the sensitivity for AI to detect CRM+ by Dr was 80%; 88% (by images; by cases), the specificity was 68%; 66% (by images; by cases). The survival curve (local recurrence rate, DFS, OS) was also superior in AI- group than AI+ group which was comparable with the results of Dr. Conclusions: Deep Learning can detect local advanced rectal cancer in CT images and prediction results also implicate poor disease outcome.
Effect of neoadjuvant chemotherapy on overall survival in stage II and stage III colon cancer: A propensity-score matched analysis of the National Cancer Database.
Authors: Horesh Nir , Emile Sameh Hany , Freund Michael , Garoufalia Zoe , Gefen Rachel , Zhou Peige , Nagarajan Arun , Wexner Steven D 
Published: June 2023

e15632 Background: Neoadjuvant chemotherapy (NAC) is currently indicated for patients with advanced colon cancer. However, there are little data regarding the impact of NAC on short-term outcomes and overall survival (OS). This study aimed to determine the role of NAC in patients with advanced colon cancer. Methods: A retrospective analysis of all patients with stage II-III colonic adenocarcinoma in the US National Cancer Database (NCDB) between 2006 and 2019. Propensity score matching was used to adjust for possible confounders. The cohort was divided into two equally matched groups: patients who received NAC and controls. The primary outcome was 5-year OS. Results: 902 (1.6% of the original cohort) patients with clinical stage II-III colonic adenocarcinoma were treated with NAC. Before matching, patients treated with NAC were significantly younger (61 vs 76 years; p < 0.001) and more often male (54.5% vs. 46.5%; p < 0.001) and had more private insurance (46.9% vs 22.6%; p < 0.001) and a lower Charlson comorbidity index score (p < 0.001). In addition, patients treated with NAC had more left-sided tumors (41.7% vs 30.1%; p < 0.001) and underwent more resections of a contiguous organ with colonic resection (27.1% vs 7.6%; p < 0.001). After matching, 620 patients were included in each group. The mean OS of patients in the NAC group was comparable to the control group (105.2 months, 95%CI: 98.1-112.2 vs 105 months, 95%CI: 98.2-111.7; p = 0.627). Stratifying OS based on clinical stage demonstrated that mean OS was significantly longer in patients with stage III (100.8 months, 95%CI 92.6-109.1 vs 88.4 months, 95%CI 79.7-97.1; p = 0.01), while the opposite effect was noted in stage II patients (106.1 months, 95%CI 96-116.3 vs 119.8 months, 95%CI 110.5-129.2; p = 0.04). Cox regression survival analysis showed that NAC was significantly associated with a lower risk of mortality (HR 0.72, 95%CI 0.64-0.8; p < 0.001). Conclusions: Preoperative neoadjuvant chemotherapy is associated with improved OS in patients with Stage III colon cancer, but not in patients with stage II disease.
Retrospective study of combined pelvic organ resection in the treatment of primary and recurrent pelvic malignant tumors.
Authors: Zhenyu Li , Zhao Yuzhou , Li Changzheng 
Published: June 2023

e15635 Background: For locally advanced or recurrent pelvic malignancies, combined pelvic organ resection has been used to treat rectal, bladder, gynecological and other related malignancies. As an interdisciplinary and high-risk operation, the perioperative safety and future information are often very limited. We retrospectively analyzed the efficacy of PE surgery in our institution. Methods: In this retrospective study, 59 patients with pelvic malignant tumors received PE surgery from July 2015 to July 2021. They were divided into two groups according to the location of the disease: rectal tumor group (n = 40) and cervical cancer group (n = 19). The baseline data, gene detection reports, pathological reports, perioperative conditions and prognosis were analyzed. The two groups were compared by independent sample t-test; Comparison between groups χ2 test, the survival curve was drawn by Kaplan-Meier method and compared by log rank test. Results: Among these 59 patients treated with PE, the rectal tumor group and the cervical cancer group did not differ significantly in terms of demographics, operative time, hospital stay, intraoperative blood loss, and rates of use of preoperative and intraoperative radiotherapy. Compared with the two groups, the overall incidence of postoperative complications was 37% in the group with rectal tumours and 26% in the group with perineal wound infection being the most common, cervical cancer 46% and urinary tract infection being the most common. Comparing the postoperative survival OS between patients in the rectal tumor group and those in the cervical cancer group, the former was better, with 5-year overall survival rates of 37% in the rectal tumor group and 28% in the cervical cancer group. Within the group of rectal tumours, however, there are differences in survival between patients with primary (LARC) and recurrent (lrrc) rectal tumours; Patients with LARC have shown a significant survival benefit postoperatively, with 5-year overall survival rates of 40% for patients with LARC and 27% for patients with lrrc. OS was significantly better in patients with well differentiated tumors, N0 stage, and high microsatellite instability (MSI). On the basis of univariate analysis, poorly differentiated tumor, regional lymph node dissemination, MSI, and no chemotherapy received perioperatively were significant predictors of poor survival (P < 0.05). Conclusions: PE is currently an effective treatment for pelvic malignancies with aggressive radical resection of lesions, which can effectively improve their cure rate, improve quality of life, and careful patient selection can optimize outcomes.
Screening the key pathogenic mutations in Chinese patients with colorectal cancers using liquid and tissue biopsy.
Authors: Wu He , Peng Huixin 
Published: June 2023

e15637 Background: Colorectal cancer (CRC) is the third most common cancer worldwide. Over the past decades, significant progress has been made in the clinical treatment of CRC. Targeted therapy is an optional approach that has successfully prolonged overall survival for CRC patients. It is necessary to determine the personalized targets for guiding the usage of specific drugs, which requires biopsy to obtain pathological samples for analysis. Both tissue biopsy and liquid biopsy are commonly used in clinical diagnosis, while each has its own advantages and limitations. The mutation detection rate of tissue biopsy is usually higher, and more genes can be detected, but most tissue biopsies require surgery to obtain samples and may be biased due to the intra-tumor heterogeneity. Liquid biopsy is less harmful to patients, but the detection sensitivity is much lower than tissue biopsy. Methods: In this study, 353 paraffin tissue section samples were used as tissue biopsy samples and 112 blood samples were used as liquid biopsy samples. All samples are from Chinese patients and are collected from December 2021 to August 2022. Whole-genome sequencing was performed, and several processes have been conducted to eliminate noise, duplicates and reads with low depth, therefore the gene mutations detected in the samples were considerably reliable. We selected APC, TP53, KRAS, PIK3CA and BRAF as the key pathogenic genes for CRC, analyzed the mutation detection results in tissue and blood samples. The detection difference between two types of biopsies was assessed using Pearson's Chi-squared test. Results: Among all samples, 21 (5.95%) tissue biopsy samples and 37 (33.04%) liquid biopsy samples did not contain any key pathogenic genes. For all biopsy samples, the detection rates for APC in tissue biopsy samples (n = 236, 66.86%) and liquid biopsy samples (n = 49, 43.75%) demonstrate significant difference (p = 2.02e-05). The differential detection rates were also observed in TP53 (n = 223 vs. n = 51, 63.17% vs. 45.54%, p = 0.0014) and KRAS (n = 183 vs. n = 39, 51.84% vs. 34.82%, p = 0.0024). There is no significant difference in detection rates of PIK3CA (n = 77 vs. n = 15, 21.81% vs. 13.39%, p = 0.0699) and BRAF. Only 25 (7.08%) tissue biopsy samples and 8 (7.14%) liquid biopsy samples were found to detect BRAF (p = 1). Conclusions: Generally, there is no doubt that the overall detection sensitivity of tissue biopsy is higher than that of liquid biopsy for CRC, and our analysis provided the statistical support. But for some relatively rare disease-causing genes, there is not much difference between the two biopsy methods. For patients, tissue biopsies can be more painful than liquid biopsies, so how to improve the detection of liquid biopsy in CRC is still a subject that requires efforts.
Proteome analysis of patients with early onset colorectal cancer in Ireland.
Authors: O Reilly Mary , Kristic Aleksandar , Murphy Catherine , Linehan Anna , Wynne Kieran , Sheahan Kieran , Winter Des C , McDermott Ray , Kolch Walter 
Published: June 2023

e15639 Background: Early onset colorectal cancer (EOCRC) is defined as colorectal cancer (CRC) in those under the age of 50. The incidence of EOCRC is rising at an alarming rate. Unlike in the USA, screening for CRC in Ireland begins at 60 years of age. It has been hypothesized that the signatures of CRC in younger populations could differ from that in elderly patients. Deep characterization of the tissue using omics profiling, including proteomics, could provide the answer to this question. Moreover, omics profiling could identify new biomarkers for patient stratification and earlier diagnosis. Methods: Forty micrograms of healthy and matched frozen tumors were taken from 8 patients with locally advanced EOCRC for whole proteome analysis. The samples were digested with trypsin and mass spectrometry was performed using data dependent analysis parallel accumulation serial fragmentation (DDA-PASEF). The raw data was searched against the Homo sapiens subset of the Uniprot Swissprot database (reviewed) with the proteomics pipeline software Fragpipe (Version 19.1) Statistical analysis was performed using Perseus software. Results: When we compared proteomes of 8 tumor tissues versus matched normal tissues, out of 5,717 protein IDs, there were more than 1,300 differentially expressed proteins. Our pathway enrichment analysis, using differentially expressed proteins, has identified a number of molecular functions altered in EOCRC samples. The most enriched signaling pathways were associated with FAT10 signaling, neutrophil extracellular trap (NET) signaling and oxidative stress response. The upstream regulator analysis (URA) has identified LASP1 and LONP1 proteins. LASP1 is known to promote CRC progression via the Hippo signaling pathway, while LONP1 is known to play a role in mitochondrial functions, metabolism, and epithelial–mesenchymal transition (EMT) in CRC cells. Importantly, the NET signaling activation in all samples suggests unfavorable immunomodulation that could stimulate cell proliferation and invasiveness. The observed activation of oxidative stress signaling components is in line with the inflammatory nature of CRC, which could signify potential response to immune checkpoint inhibitors. Conclusions: Our findings in a small cohort of patients indicate that proteomics can provide a deeper insight into aberrant signalling in EOCRC. We have identified novel vulnerabilities that might be used as therapeutic targets as well as patient stratification biomarkers. Additional proteome studies with corresponding genomic and transcriptomic analysis are needed to fully understand the potential of this approach.
Circulating levels of the pro-inflammatory monomeric isoform of C-reactive protein (mCRP) correlate with inflammatory markers in patients with stage II-III colon cancer.
Authors: Fuglestad Anniken Joerlo , Bousquet Paula Anna , Køstner Anne Helene , Meltzer Sebastian , Ree Anne Hansen , Fernandez-Botran Rafael , Kersten Christian 
Published: June 2023

e15641 Background: Tumor-promoting inflammation is an established hallmark of cancer. C-reactive protein (CRP) is one of the most studied negative prognostic markers of the systemic inflammatory response (SIR) and known to be implicated in detrimental immune responses. Circulating CRP, as measured in routine practice, is a pentameric structure (pCRP). However, when pCRP binds to activated membranes, the protein dissociates into subunits termed monomeric CRP (mCRP). Pro-inflammatory characteristics of mCRP have been reported to be stronger than for pCRP. While a role for mCRP in cancer has been proposed, the circulating level of mCRP has never been investigated in cancer patients. Our aim was to detect and quantify plasma mCRP of patients diagnosed with stage II-III colon cancer (CC) and investigate possible correlations with other inflammatory markers. Methods: 40 patients treated for stage II-III CC between 2012 and 2015 at Sorlandet Hospital, Norway, were included in the study. 20 patients had pCRP level < 10 mg/L and 20 patients had pCRP > 10 mg/L, the latter interpreted as presence of SIR. Levels of pCRP and albumin were captured at the time of diagnosis. Pre-operative mCRP and the cytokines IL-6, IL-8 and TNFa were all measured using EDTA plasma samples. Pre-operative mCRP levels were measured by a specific ELISA employing reagents kindly provided by Drs. L. Potempa and I. Rajab (Roosevelt University, Schaumburg, IL). Results: Of the 40 patients, 47.5% were female, 57.5% had right-sided primary tumor and 50.0% were stage III. Median values (min-max) were for mCRP 2.55 ng/mL (0.00-10.9), pCRP 9.95 mg/L (0.50-136), IL-6 5.10 pg/mL (2.60-25.1), IL-8 4.95 pg/mL (0.40-32.4), TNFa 5.90 pg/mL (3.10-29.5) and albumin 40 g/L (29.0-46.0). Conclusions: To the authors’ knowledge, this is the first time mCRP has been reported in systemic circulation of cancer patients. Our study shows plasma mCRP to be quantifiable in CC patients, albeit at very low levels. This may be due to its reduced aqueous solubility and supports the notion of mCRP as a circulating particle-bound or tissue-associated isoform. However, despite low circulating mCRP levels and a small number of patients, mCRP still correlated with other well-known SIR markers with proven negative prognostic value in cancer patients, supporting its potential role as a pro-inflammatory player in CC. Further studies correlating SIR with circulating and tissue-bound mCRP are currently being performed. [Table: see text]
Circulating tumor DNA guided therapeutic strategies for colorectal cancer patients with multiple small pulmonary-limited nodules: An open-label, prospective, phase II cohort study.
Authors: Chang Jinjia , Li Wenhua , Jian Qijie , Pang Fei , Li Feng , Wang Kai , Peng Junjie 
Published: June 2023

e15645 Background: The clinical diagnosis and treatment of small pulmonary nodules (suspected to be lung metastases) in advanced colorectal cancer (CRC) patients remain controversy. Previous studies have shown that tumor-informed circulating tumor DNA (ctDNA) testing with blood sample can sensitively detect recurrence or metastasis of CRC patients. This study was designed to explore the clinical value of tumor-informed ctDNA test in metastatic CRC patients with small pulmonary-limited nodules. We aimed to identify the low-risk patients for de-escalation therapy, as well as high-risk patients with no evidence of disease (NED) for escalation therapy. Methods: This is an ongoing, open-label, prospective and phase II cohort study (NCT 05495672). According to the longest diameter of the pulmonary nodule, patients were divided into two cohorts: Cohort 1(0-1cm) and Cohort 2 (1-2cm). Tumor-informed ctDNA test (OriMIRACLE S) would be performed every three months until progression or 2 years. The treatment strategy of each patient is decided by a multidisciplinary team depending on ctDNA and lung CT scan results. In general, negative minimal residual disease (MRD) patients will receive only regular follow-up. Patients with positive MRD will receive intensive examination and local treatments for pulmonary nodules such as surgery, radio frequency ablation or stereotactic body radiotherapy combined with or without systemic therapeutic treatment, aiming to achieve NED or cure. Results: From June 2022 to December 2022, a total of 26 patients were screened in the group, one patient was eliminated (with extrapulmonary metastasis), and a total of 25 patients were successfully enrolled. At present, 1 patient died (by acute intestinal perforation), 4 patients were excluded from the group (with the emergence of extrapulmonary metastasis), and a total of 20 patients were in the group. The positive rate of MRD in baseline were 4/11(36.4%) for Cohort 1 and 10/14 (71.4%) for Cohort 2, respectively. Notably, in Cohort 1, 3 of 4 patients with positive MRD at baseline were examined extrapulmonary metastasis during the follow-up examination. Conclusions: Our preliminary results suggested that the positive rate of MRD were higher in Cohort 2 than Cohort 1. Patients with pulmonary nodule less than 1 cm tended to develop extrapulmonary metastasis if baseline MRD was positive. In such circumstances, more intensive follow-up examination is suggested to prevent early disease progression. Clinical trial information: NCT05495672 .
Efficacy and safety of camrelizumab and apatinib combined with neoadjuvant concurrent chemoradiation for MSS locally advanced rectal cancer.
Authors: Jiang Tao , Wang Dongsheng , Cheng Jingjing , Wei Xiaojuan , Fu Jialei , Cao Lianjing , Lei Peijie , Zhang Xianxiang , Gao Yuan , Hu Jilin , Zhang Hongjun , Cao Bin , He Baoguo , Mao Qingdong , Qi Peng , Wang Jigang , Zhou Xiaoming , Tan Junying , Lu Haijun 
Published: June 2023

e15647 Background: Long-term neoadjuvant concurrent chemoradiotherapy (CRT) is the standard therapy for local advanced rectal cancer (LARC).However, the pCR rate is only about 15 %. Immune checkpoint inhibitors (ICIs) and antiangiogenic agents have shown activity in advanced rectal cancer, but their efficacy in the neoadjuvant setting is unclear. In this exploratory trial, we evaluate the efficacy and safety of a combination of ICI (Camrelizumab), anti-angiogenesis (Apatinib) and CRT for neoadjuvant treatment of microsatellite-stable (MSS) LARC. Methods: Patients in experimental group received Camrelizumab injection combined with Apatinib tablets and concurrent CRT. Radiotherapy dose: 5040cGy/28f/180cGy; Capecitabine 825 mg/m2 bid on the radiotherapy day; Apatinib 250mg qd d1-d60; Camrelizumab 200 mg q3w, d22, d43, d64. Surgery with total mesorectal excision was performed 7-9 weeks after the end of CRT. The primary endpoint was pCR rate and the secondary endpoints included major pathological response (MPR) rate, R0 resection rate, 2-year DFS rate, 3-year OS rate and safety. Results: From July/2022 to October/2022, a total of 11 patients were recruited and assessed, 90.91% (10/11) of which is at high-risk (cT3 with any MRF involved, any cT4a/b, lateral node +, HLARC). Out of the 11 patients evaluable for pathological response, 4 (36.36%) patients achieved a pCR (AJCC grade 0) and 7 (63.64%) obtained a MPR(AJCC grade 0+1)(table). All patients achieved R0 resection and downstaging. Treatment-related severe adverse events were observed in 3 patients (grade 3-4 transaminase elevations); all fully recovered and received radical surgery. No treatment-related deaths were observed. Conclusions: A promising pCR rate of 36.36%, with mild toxicities, was shown in MSS LARC patients treated with neoadjuvant Camrelizumab combined with Apatinib and long-term CRT plus radical surgery, suggesting the candidate therapy for the future non-surgical approach. Clinical trial information: ChiCTR2100053040 . [Table: see text]