bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of patients at the Memphis VA Medical Center with positive FIT testing and incomplete GI evaluation during the COVID-19 pandemic.
Authors: Mitchell Mark , Huynh Richard , Lands Lindsey , Weir Alva B 
Published: June 2023

e15542 Background: In 2020, colorectal cancer was the second leading cause of cancer death in the United States 1. In March 2020, the COVID pandemic began which led to widespread disparities in health care, such as surveillance colonoscopies 2. A Veterans Health Administration large data review revealed completion rates of colonoscopy for high risk individuals, including positive fecal immunochemical test (FIT) to be unchanged pre-pandemic and during the pandemic at 27% vs 26.5% 3. Another study reports a non-VA population completion rate within 360 days pre-COVID compared to COVID was 53.9% vs 44% 4. This research sought to analyze data through a retrospective chart review from the Memphis VA Medical Center, the timing of screening colonoscopies after a positive FIT and reasons for delay in obtaining these. Thereby, evaluating effectiveness in completing the procedures and change effected by the COVID pandemic. Methods: A retrospective cohort study designed to detect rates of completed colonoscopy during and before the COVID pandemic after a positive FIT. Records were reviewed of all positive FIT from 2 specified time frames at the Memphis VA to evaluate completion of colonoscopy after a positive FIT. The charts of 157 VA patients with positive FIT during the pandemic were compared to the charts of 115 VA patients with positive FIT pre-pandemic for colonoscopy completion, evaluating both completion rates within 180 days and chart identified reasons for lack of completion. Both community (CITC) and VA procedures for veterans were included. One tailed Fisher’s exact test was applied to calculate the completion rate difference. Results: Overall completion rate of colonoscopy was 46% in the pre-COVID and rose to 56% in the COVID period [p-value < .05 (.0665)]. Percentage of timely completion ( < 180 days) was 26% pre-COVID, compared to 47% during COVID. Percentage of delay ( > 180 days) in pre-Covid was 74%, compared to 53% during COVID. [p-value < .05 (.0004)]. Reasons for delay both pre-COVID and during COVID are listed below. Conclusions: It can be concluded that there is a statistically significant increase in timely colonoscopy completion during the studied COVID period when compared to the pre-COVID period. The total completion rate was higher at our institution than in the literature, likely due to our inclusion of community colonoscopies and our aggressive case management system. A common reason for delay in all groups was delay/lack of referral. This cause for delay should be improved with additional steps in our case management policy. [Table: see text]
Genomic analysis of RAS and BRAF mutation in an oncology reference hospital in Brazil.
Authors: Amorim Guilherme , Medeiros Maria Clara Rodrigues Lima , Ferreira Mariana , Medeiros Ana Maria Rodrigues Lima , Bighetti Bruna , Forones Nora Manoukian , Tadokoro Hakaru 
Published: June 2023

e15545 Background: Colorectal cancer (CRC) is a common malignancy worldwide and a leading cause of cancer-related deaths. The molecular basis of CRC can guide patient prognosis and therapy. Unfortunately, knowledge on the CRC mutation landscape is limited. In this study, we investigated the mutation profile of related genes by next-generation sequencing and associated with microsatellite instability (MSI) in a series of 43 Brazilian CRC patients from 2016 to 2022, of a Public Oncology Hospital. This study aimed to analyze the frequency of mutation covariates of the KRAS and BRAF genes and their correlation with survival data in patients diagnosed with metastatic RCC. Methods: We conducted a retrospective, observational and descriptive study in 43 patients diagnosed with CRC treated at an Oncology Reference Hospital in Brazil. DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tumor tissues. Targeted sequencing was performed using a customized panel for CRC-related genes. The mutation data was analyzed in relation to clinicopathological features, MSI status and survival, using the Kaplan-Meier method and log-rank test. Results: RAS mutations were found in 37.2% of patients and BRAF mutations in 9.3%. The analysis of most secondary clinicopathological features did not show statistical prognostic impact. In general analysis, the age and presence of BRAF mutation were related to the increased risk of death HR-0.31 (0.11-0.82). However, among patients with BRAF mutations exclusively, the age did not represent an increased risk of death. Concerning our RAS mutations, as we already knew from previous literature data, the variety is diverse. We noticed nine different RAS alterations, in which the most prevalent was the G12D (33%), followed by G13D, Q61K and G12A. The distribution of our RAS alteration and prevalence is summarized in the table below: Conclusions: Our findings are consistent with previous studies concerning frequency and patterns of RAS and BRAF mutations in CRC. The identification of MSI and the evaluation of genetic ancestry may help to guide treatment decisions in CRC patients. At present, it is already known that some of RAS mutations are targets for selective RAS drugs and may have better outcomes the pan-RAS drugs. Our study provides important insights into the mutation profile of related genes in Brazilian CRC patients and these findings have implications in clinical management of CRC. Further studies with larger cohorts are needed to validate our findings. [Table: see text]
ScRNA-seq to examine heterogeneity of transcriptional regulation of CAFs between left-sided and right-sided CRC.
Authors: Fan Tongqiang , Wang Qian , Wang Tao , Xiao Shanshan 
Published: June 2023

e15548 Background: Cancer-associated fibroblasts (CAFs) play prominent and diverse tumor-promoting function roles in tumor microenvironment (TME) and influence cancer hallmarks, but without systematic investigation between left-sided and right-sided CRC (colorectal cancer). Methods: We collected a public scRNA-seq dataset (Pelka et al., 2021) with 21 samples from left-sided CRC and 79 from right-sided CRC. Only CAFs were extracted for downstream analysis. Seurat (Stuart et al., 2019), Monocle2 (den Berge et al., 2020) and pySCENIC (Aibar et al., 2017) were used to perform dimensionality reductions, differential analysis, pseudo-time trajectory analysis, and the transcriptional regulation analysis, respectively. Results: Firstly, we performed differential analysis on 2,049 cells from 62 of 100 samples that contained CAFs. The results showed that highly expressed genes including IGFBP1, IGFBP2, LCN2, ALDH1A1 and CASP1 in left-sided CRC were mainly enriched in immune response pathway, while up-regulated genes in right-sided CRC were neutrophil-migration-chemotaxis-related such as PPBP1, PF4V1, CCL7, CXCL3 and CXCL8. Then, we classified 2,049 CAFs into four subclusters based on the markers of CCL8+ CAF, CXCL14+ CAF, GREM1+ CAF and MMP3+ CAF. The proportion of CXCL14+ CAF was higher in left-sided CRC while MMP3+ CAF was preferentially enriched in right-sided CRC, which was also independently validated by 33 TCGA cohorts. Further investigation on those subclusters showed that CXCL14+ CAF was myCAF, while the rest (CCL8+ CAF, MMP3+ CAF and GREM1+ CAF) were iCAF. After investigating the heterogeneity of CAFs, we focused on the transcriptional regulatory networks (TRNs). The results showed that the dominant regulons in left-sided CRC ( HOXD9, HSF2, MYBL1, HES6, XRCC4, and ZNF585B) and right-sided CRC ( CREB5, ZNF274, IRF7, TFEC, NR2F1, and PITX3) were distinct, which highlighted the heterogeneity and plasticity of CAF-based TRNs between left-sided and right-sided CRC. Conclusions: Collectively, although further experimental verification is required to establish the functional roles of each CAF cluster and the diverse origins of CAFs, this study may facilitate better understanding molecular mechanism of CAF-targeted therapy strategies in CRC.
Trends of colorectal cancer and associated factors in the United States: A SEER registry analysis.
Authors: Fatima Ifrah , Ponvilawan Ben , Grover Dheera , Kahn Adriana Matutino , Shrestha Anuj , Dharan Murali 
Published: June 2023

e15553 Background: Colorectal cancer (CRC) is the fourth most common type of cancer diagnosed in the US, accounting for 8% of new cancers diagnosis in 2022. Despite advancements in the screening and diagnostic methods, CRC still contributes significantly to cancer-related healthcare burden ($24.3 billion/year). Several factors including wider demographic reach, socioeconomic equity, age at screening, CRC awareness, and social media platforms have contributed to this changing landscape. We conducted a Surveillance, Epidemiology, and End Results Program (SEER) based analysis to determine the trends of CRC diagnosis and potential risk factors. Methods: Individual data was acquired from SEER 9 registry from 1975-2018. R was used for the statistical analyses. Univariate logistic regression was performed to evaluate the relation between year of diagnosis and each variable (year of diagnosis, household income, household location, sex, and race) at the time of diagnosis. Multivariate regression was performed for individuals in all age group and less than 45 years of age. P-value less than 0.05 was considered significant. Results: In total 550,221 CRC patients were retrieved. 91.7% (504,709) were ≥50 years and 4.5% (24,674) were < 45. Over the years, there was a notable increase in percentage of patients with age < 45 years amongst all CRC patients (3.3% in 1975-1979 vs. 7.4% in 2015-2018) with females increasing faster than males. A remarkable drop in percentage of CRC case in individuals ≥50 years amongst all gastrointestinal cancers (63.0% in 1975-1979 vs. 44.8% in 2015-2018) with females decreasing faster than males. There were no interactions between the year of diagnosis and above variables. Multivariate logistic regression exhibited lower odds of CRC diagnosis in all non-white races and males, but higher odds in lower household income and non-metropolitan areas (Table 1). Subgroup analysis of age group < 45 years pertained similar odds. Conclusions: The striking drop in number of CRC cases above 50 years of age can be attributed to earlier detection with screening methods, and other socioeconomic factors like healthcare literacy and awareness. Increased representation of younger population over the years reaffirms the recent change in guidelines for screening. Further studies focusing on determining the impact in outcomes of screening methods in younger population and equality of implementation in disadvantaged population are highly warranted. [Table: see text]
Efficacy of vemurafenib based regimens in colorectal cancer: A systematic review of clinical trials.
Authors: Aiman Wajeeha , Qirem Murad , Alkhlaifat Osama , Garcia Jose , Asfeen Ummul , Jumean Samer , Rayad Mohammad Nabil , Veeraballi Sindhusha , DaCosta Theodore , Guron Gunwant K. , Shaaban Hamid Salim 
Published: June 2023

e15566 Background: Colorectal cancer (CRC) is the 3rd most common cancer worldwide, and BRAF gene mutation is present in almost 10% of these cancers. It results in constitutive activation of the mitogen-activated protein kinase pathway (MAPKP). Abnormal activation of MAPKP leads to uncontrolled mitotic activity and inhibition of apoptosis. In this systematic review, we will assess the efficacy of vemurafenib (BRAF inhibitor) based regimens in CRC. Methods: We followed PRISMA guidelines to conduct this systematic review. A literature search was performed on PubMed, Clinicaltirals.gov, and Embase with mesh terms, ‘’Colorectal Neoplasms’’ and “Proto-Oncogene Proteins B-raf” from the inception of data till 01/05/2023. We screened 4572 articles and included 1 randomized clinical trial (RCT, N = 100), and 4 non-randomized trials (nRCTs, N = 85), measuring the efficacy of vemurafenib (V) based regimens in BRAF V600E-mutated CRC. Results: In 5 clinical trials (N = 185), 90 patients were treated with triple therapy, 45 with dual therapy, and 50 were in the control arm. In triple therapy, 69 patients were treated with V plus irinotecan (I) and cetuximab (C), overall response rate (ORR) was 17% and 35%, and progression-free survival (PFS) was 4.2 and 7.7 months in the randomized and the non-randomized study, respectively. PFS was improved significantly with a hazard ratio (HR) of 0.50 (95% CI, 0.32 to 0.76, P = .001) in favor of V+I+C compared to C+I. Among combinations of V+C, adding 5-fluorouracil/leucovorin/irinotecan (FOLFIRI) as third combination showed the highest ORR of 81% and overall survival (OS) and PFS of 15.4 and 9.7 months, respectively. In two drug regimens, V was combined with Cobimetinib (Co) and Panitumumab (P) in two non-randomized studies, and partial response (PR) was 26% and 13%, respectively. (Table 1). Conclusions: BRAF + EGFR inhibitor combination is showing promising antitumor effects, and the addition of the FOLFIRI regimen was more effective than adding irinotecan alone while comparing treatment regimens in BRAF V600E-mutated CRC patients with metastasis. V+Co showed antitumor effects in CRC BRAF mutated patients who were heavily pre-treated. More randomized trials needed. [Table: see text]
Efficacy and safety of regorafenib plus biweekly TAS-102 for refractory metastatic colorectal cancer (REGTAS): A multicenter single-arm phase II trial.
Authors: Wang Xiangling , Li Zhen , Sha Dan , Ren Haipeng , Yi Cuihua , Li Shuguang , Wang Peng , Chu Yunxia , Wang Jian , Yang Xiaorong , Hao Jing 
Published: June 2023

e15567 Background: Both regorafenib and TAS-102 have shown significant, but limited survival benefits for metastatic colorectal cancer (mCRC) patients who progressed after standard treatments. Due to their unique mechanisms of action and non-overlapping toxicities, a preliminary phase I study (REMETY) has demonstrated that regorafenib combined with TAS-102 in a four-week standard schedule was feasible and safe, but at the cost of recommended phase II dose of TAS-102 being 25 mg/m2 BD. This study aimed to evaluate the efficacy and safety of biweekly TAS-102 plus regorafenib in refractory mCRC. Methods: REGTAS is a multicenter phase II trial involving patients with chemo-refractory mCRC. Prior treatment with 5-FU, oxaliplatin, irinotecan, anti-VEGF antibody and anti-EGFR antibody for RAS wild type was required. Regorafenib was administered at 120 mg/day for 21 days in a four-week cycle, or a dose-escalation strategy (80 mg/day, followed by weekly increase of 40 mg to 120 mg/day). TAS-102 was given biweekly (30mg/m2 BD, on Day 1-5). The primary endpoint was progression-free survival (PFS). The secondary endpoint included safety, disease control rate (DCR) and overall survival (OS). Results: From March 1st 2022 to December 31st 2022, 16 patients were enrolled form five centers. All patients received at least one cycle of treatment, and 13 patients had at least one evaluation. The median age was 56.5 years old including 9 (52.9%) males. 11 (68.7%) patients were enrolled within 18 months from diagnosis of mCRC. RAS and BRAF mutation were detected in 8 (50.0%) and 1 (6.3%) patients. Among 13 evaluable patients, 11 achieved SD and 2 had PD, with the DCR of 84.6% (95% CI: 54.6%-98.1%). The median PFS was 4.9 months (95% CI: 2.8-7.0). Twelve patients were alive, and the median OS was not reached. All patients experienced treatment-related adverse events (TRAEs) and 4 (25.0%) had grade 3 or higher TRAEs. No grade 5 TRAE occurred. The most common TRAEs of any grade were hand-foot syndrome (62.5%), hypertension (68.8%), fatigue (50.0%), neutropenia (43.8%), thrombocytopenia (31.3%) and alanine aminotransferase increased (25.0%). Conclusions: Regorafenib plus biweekly TAS-102 exhibited promising benefits in terms of DCR and PFS, and could be a novel treatment option for patients with refractory mCRC. The adverse events were generally tolerable and manageable. Further studies are needed to confirm these preliminary findings. Clinical trial information: The registration number is still under approval .
Total neoadjuvant therapy for locally advanced rectal cancer: A western Australian experience.
Authors: Oey Oliver , Khattak Adnan , Ferguson Tom , Theophilus Mary , Tiong Siaw Sze , Ali Sayed , Khan Yasir 
Published: June 2023

e15582 Background: Despite the widespread application of standard chemoradiotherapy (CRT) followed by total mesorectal excision with adjuvant chemotherapy, the mortality reduction for locally advanced rectal cancer (LARC) has slowed in recent years. Total neoadjuvant therapy (TNT) is a novel therapeutic strategy in LARC which incorporates both systemic chemotherapy and neoadjuvant CRT prior to surgery. Recent studies have associated TNT with better treatment adherence, decreased toxicity, improved complete clinical response and anal sphincter preservation rates. However, real-world experience with TNT in the management of LARC remains limited. Methods: Records from patents with LARC who underwent TNT at two oncology centres in Western Australia since 2018 were screened. Patient demographics, diagnostic workup, treatment regimens, surgical, pathological reports, post-operative surveillance scans and adverse effects’ documentation were reviewed. TNT regimens included neoadjuvant chemotherapy (NAC) with oxaliplatin in combination with either 5-FU (FOLFOX) or capecitabine (CAPOX) with chemoradiation given prior or after NAC, which is then followed by surgery. Patients who had radiological complete response (rCR) were given the option of “watch and wait (W&W)” instead of proceeding to surgery. Outcomes assessed included radiological complete response (rCR), pathological complete response (pCR) rate, proportion of patients with progressive disease, type of surgery, rate of R0 resection, proportion of patients who completed planned cycles of chemotherapy and radiotherapy and treatment-related adverse effects. Results: 29 patients with LARC have thus far have completed TNT followed by surgery. The mean age was 59 years (range 34-84), 58% and 42% of patients were male and female respectively. 11 (38%), 16 (55%) and 2 (7%) patients were ECOG 0, 1 and 2 respectively. The majority of patients were stage 3 (90%), with the remaining 3 patients at stage 1, 2 and 4 at time of presentation. 3 (10%) and 7 (24%) patients had pCR and rCR respectively, of which 4 opted for W&W approach. Treatment was well-tolerated with 86% and 96% of patients completing the planned total course of chemotherapy and radiotherapy respectively although dose reductions and/or delay were required for many. Common adverse effects included neuropathy, neutropenia, anaemia and fatigue, most of which were grade 1. Of the 22 patients who underwent surgery, 19 (82%) and 4 (18%) patients had R0 resection and R1 resection respectively. Majority of the patients who underwent surgery had an anterior resection with temporary loop ileostomy (64%) while the remaining had an abdominoperineal resection (36%). After a median follow up time of 27 months, 10 (34%) patients had progressive disease. Conclusions: TNT is a well-tolerated, effective and promising strategy for the management of LARC. Further data is needed to determine the standard TNT protocol.
Circulating tumor DNA in decision-making of patients with metastatic colorectal cancer after failure of first-line treatment containing cetuximab: A single-center, phase II trial.
Authors: Zou Jianling , Yang Wentao , Li Wenhua , Zhang Jieyun , Geng Qirong , Chang Jinjia , Wang Chenchen , Hu Xin , Chen Zhiyu 
Published: June 2023

e15584 Background: Genetic status is constantly changing after receiving cetuximab. To analyze the molecular characteristics in mCRC after first-line treatment containing cetuximab and adjust second-line targeted therapy strategies, we conducted this prospective study. Methods: Patients with measurable mCRC were enrolled. Main eligibility criteria included initial RAS and BRAF wild-type genetic status on tumor tissue; prior first-line regimens including cetuximab, and then showed progression disease. The ctDNA status was detected: bevacizumab would be applied if there was RAS mutation; the combination of vemurafenib, cetuximab and irinotecan would be used if there was BRAF mutation; trastuzumab would be used if there was HER2 amplification; cetuximab or bevacizumab would be applied according to investigators discretion if no related secondary variation. The primary endpoint was ORR; secondary endpoints were DCR, PFS, OS, safety and tolerability. Results: Twenty-two patients were enrolled from Apr 8, 2021 to Nov 18, 2022. Fifty percent (11/22) were males and the median age was 56.5 years. 59.1% (13/22) patients received bevacizumab, 36.4% (8/22) patients received cetuximab, and 4.5% (1/22) patients received trastuzumab and pyrotinib. 52 variations were detected in 22 patients before second-line therapy, with a positive rate of 95.5%. TP53 (90.9%, 20/22) was the most mutated gene, followed by APC (86.4%, 19/22). The percentage of secondary KRAS mutation was 9.1% (2/22), BRAF mutation was 0, ERBB2 amplification was 4.5% (1/22), and ERBB2 mutation was 9.1% (2/22). For 8 patients with serial ctDNA detection, the number of gene variation was decreased during disease remission (10 vs. 23) and increased again during progression (23 vs. 10). The ORR was 40.9% (9/22) for all patients. And it was 38.5% (5/13) and 37.5 % (3/8) separately for patients received bevacizumab or cetuximab (p = n.s.). The DCR was 86.4% (19/22) for all patients. And it was 92.3% (12/13), and 75% (6/8) for patients received bevacizumab or cetuximab separately (p = 0.013). The median PFS was 8.6 months in all patients. And it was 11.6 months and 4.6 months separately in patients received bevacizumab or cetuximab (p = 0.013). The median OS was 12.4 months in all patients. And it was 14.5 months and 11 months separately in patients received bevacizumab or cetuximab (P = 0.27). In addition, no difference in treatment related serious adverse advents grade 3-5 was observed. Conclusions: Circulating Tumor DNA is a promising biomarker for assessing treatment efficiency and guiding second-line treatment decisions in patients with mCRC. The bevacizumab-based second line treatment increases DCR and PFS than continuously cetuximab-based treatment, and had a better tendency in OS. Clinical trial information: NCT04831528 .