bluuebunny/crossref_metadata_2025_split huggingface dataset:
When is neoadjuvant chemotherapy indicated in rectal neuroendocrine tumors? An analysis of the National Cancer Database.
Authors: Gefen Rachel , Emile Sameh Hany , Horesh Nir , Garoufalia Zoe , Freund Michael , Wexner Steven D 
Published: June 2023

e15631 Background: Rectal neuroendocrine tumors (rNET) are rare and challenging to manage. While most patients with small rNET can be definitively treated with local excision, the role of chemotherapy in general and neoadjuvant therapy specifically in managing advanced rNET has not been well established. Therefore, this study aimed to determine which patients with rNET may gain a survival benefit from neoadjuvant chemotherapy. Methods: A retrospective cohort analysis of all patients who underwent surgical resection of rNET in the US National Cancer Database (NCDB) (2004-2019) was performed. First, univariate and multivariate cox regression analyses were performed to determine the independent predictors of poor overall survival (OS) and define the high-risk groups. Afterwards, stratified OS analyses were performed for each high-risk group to assess whether neoadjuvant chemotherapy had a survival benefit in each group. Results: 1837 patients (49.8% female; mean age 56.6 ±12.3 years) underwent radical resection of a rectal neuroendocrine tumor. Tumors > 20 mm in size, clinical T4 tumors, poorly differentiated tumors, and metastatic disease were independent predictors of worse OS and were defined as high risk groups. Neoadjuvant chemotherapy did not have a significant survival benefit in any of the high-risk groups, except for patients with high-grade rNETs where neoadjuvant therapy significantly improved OS to a mean of 30.9 months compared to 15.9 months when neoadjuvant therapy was not given (p = 0.006). Conclusions: Neoadjuvant chemotherapy improved OS of patients with high-grade rNET by 15 months and may be indicated for this group.
Comparison of concomitant mutational of type I/II/III BRAF mutation in colorectal cancer between Chinese and Western populations.
Authors: Huang Yingying , Zhongkang Li , Zhao Yun-Bo , Jia Wenzhuo , Du Jun , Zhao Gang , Wu Guoju 
Published: June 2023

e15634 Background: BRAF V600E CRC had a relatively poor prognosis.The efficacy of BRAFi is unpredictable just that intrinsic genetic complexity and partially unknown reason.Therefore, To understand co-mutation mechanism can help improve treatment and follow-up strategy. Methods: 339 Chinese CRC patients and 125 Western CRC data from the cBioPortal were included in study. Co-occurrence mutation analysis, GO and KEGG pathway enrichment analysis was enabled in this study. Results: 35/339 (10.32%) patients were BRAF mutation, with 17 patients were BRAFV600E in Beijing hospital. Patients with BRAF mutation had significantly associated with TMB-H (p = 0.0004) and MSI (p = 0.0003) than those with BRAF wild-type. In 125 BRAF mutation western cohort, The frequency clinicpathologic features, MSI, TMB, and BRAF mut-type were consistent with Chinese data. However, the primary tumor location showed significant statistical differences (P < 0.0001). In Chinese cohort, class 1 (BRAFV600E, A deeper classification system of BRAF mutations) were more likely to occur in Elder, Female, western cohort was consistent with above. Other clinicpathologic features were not associated with mut-type in Chinese cohort. However, Western cohort showed class 1 exhibited primary sample type predominance(vs class NA, P < 0.05; vs class 3, P < 0.05). Right-sided was more likely to occur in class 1(P < 0.05), this was inconsistent with the data analyzed above. Meantime, The data showed TMB-H (57.69% vs 11.76%, P < 0.001) and MSI-H (28.21% vs 14.29%, P < 0.005) of the class 1 were significantly higher, compared with class 3. In concurrent oncogenic mutations. Compared with non-class 1, class 1 were more likely co-passenger mutation. Data from Western populations show similar results. We also found that the class 1 was mutually exclusive with co-KRASmt in CRC, and co-APCmt appeared more frequently in non-class 1. In pathway enrichment, KEGG pathway showed that fewer proto-cancer signaling pathways were enriched in the class 1, which further confirmed that this type had stronger tumorigenicity. GO enrichment also proved that class1 had stronger tumorigenicity. Finally, Prognostic analysis showed median overall survival(OS) of 47.57 months in class 1 versus 19.43 months in non-class 1(p = 0.0002). Further study showed that the mOS of class 1/2/3/NA was 19.43 months, 28.50 months, 47.57 months and NA months(P = 0.0001), respectively. Conclusions: This study shown class 1/non-class 1 BRAF mutation in CRC have significantly differences in co-mutation features, genomic markers and prognioses. Especially, class I BRAF mutation in Chinese patients have higher TMB and MSI,maybe we could choose BRAFi and immunotherapy for them. Understanding BRAF mutation types and co-mutation mechanism will contribute to accurately grasp treatment, follow-up strategies and promote the development of precision therapy for CRC in the future.
Differences of RAS/BRAF mutations between ISCC and RSCC in a Chinese population.
Authors: Chen Yuhong , Qiu Yixian , Zhang Yanrui , Zhang Yun , Liang Xiayuan , Lou Feng , Cao Shanbo , Qin Jiayue 
Published: June 2023

e15636 Background: According to the location and different clinical manifestations, colon cancer can be divided into left-sided colon cancer (LSCC) and right-sided colon cancer (RSCC). There are significant differences in morphology, molecular biology, and drug sensitivity between these two type. In addition, colorectal cancer is associated with the mutation of many essential tumor suppressor genes, such as proto-oncogene (KRAS), serine/threonine protein kinase (BRAF), etc. At that point, this study retrospectively analyzed the RAS/BRAF mutation landscape and studied the gene expression differences between RAS/BRAF-mutant and wild-type patients respectively in LSCC and RSCC, to provide some reference for potential treatment plans. Methods: We retrospectively profiled the somatic mutations of 497 patients with colon cancer from the General Hospital of Southern Theatre Command and the TCGA database using 808-gene-panel target-capture next-generation sequencing. Tumor mutation burdens (TMB) were calculated using an Acornmed panel with 808 cancer-related genes. Results: Among 415 LSCC, 48.7% (n = 202) patients harbored RAS mutations, of which 183 carried KRAS mutations and 19 had NRAS mutations. Five main subtypes of KRAS mutation were detected including G12D (28.7%), G12V (17.5%), G13D (13.2%), A146T(8.5%), G12C (7.9%). 3% (11) of LSCC patients were found to have BRAF mutation, including BRAF V600E(63.6%), D594G(18.2%), G466E(9.1%), K601E(9.1%). We explored differentially expressed genes between RAS/BRAF-mutant and wild-type patients. The top5 mutant genes found only in LSCC RAS/BRAF-mutant cohort include JAK2(3%), TERT(2%), MSH6(2%), KMT2A(1%), NOTCH1(1%). In contrast, genes found only in LSCC patients with RAS/BRAF wild type include LATS2(2%), SMARCA4(2%), CBL(1%), SLX4(1%), CDKN2A(1%). Among 82 RSCC, 50% (41) patients harbored RAS mutations, of which 39 carried KRAS mutations and 2 carried NRAS mutations. 9% (39) of RSCC patients were found BRAF mutation, and the BRAF V600E was the only subtype found in the RSCC. In terms of differentially expressed genes, the top5 mutant genes found only in RAS/BRAF-mutant RSCC include NSD1(6%), ASXL2(4%), BARD1(4%), PPP2R1A(4%), SPRED1(4%), while genes found only in RAS/BRAF wild-type RSCC include ERBB2(17.6%), DICER1(11.8%), EP300(11.8%), ARID2(9%), BRIP1(9%).The TMB of RAS/BRAF wild-type RSCC patients was 33.2 mut/Mb, significantly higher than that of RAS/BRAF wild-type LSCC patients (7.0 mut/Mb, P = 0.01). Conclusions: RAS mutation and subtype were almost the same in LSCC and RSCC cohorts. BRAF mutation mainly occurred in RSCC, and the mutation subtype in RSCC was found only V600E, but we found three other BRAF subtypes D594G, G466E, and K601E in the LSCC cohort. Considering the differential expression genes in RAS/BRAF-mutant and wild-type cohorts in RSCC and LSCC patients, there may be more options for genetic targets in the future for LSCC and RSCC treatment.
Capecitabine-oxaliplatin (CAPOX) prior to chemoradiotherapy (CRT) and surgery in magnetic resonance imaging (MRI)-defined poor-risk rectal carcinoma (PRRC): A single center experience.
Authors: Ribes Carla Bellido , Soler Jorge , Ruiz Nuria , Rubio Novella Silvia , Morillo Virginia , Molina Jorge , Busquier Hernandez Isabel 
Published: June 2023

e15638 Background: Clinical trials have studied the efficacy and safety of neoadjuvant chemotherapy (CT) and CRT in PRRC. Chau published his data on PRRC studied with MRI: tumors within 1 mm of mesorectal fascia, T3 at or below levators, tumors extending > 5 mm into perirectal fat, T4 and T1-4N2 tumors (JCO 2006; 245: 668-674). Following this strategy, we present the data from our center. Methods: between February 2006- July 2018 we treated 77 PT with MRI-defined PRRC with CAPOX x 4 cycles, Capecitabine-radiotherapy, surgery and capecitabine 4 cycles (Chau strategy). Results: Our sample includes 43 men and 34 women, median age 59 (range 31-77). A patient died after the first CAPOX due to a hemorrhagic stroke. 69 PT had symptomatic improvement with CT, without identifying any progression. Surgery has performed in 75 PT and 65 had R0 resection, R1 in 6 patients, R2 in 2 patients and 2 lost. On an intent-to-treat analysis, pathological complete responses was achieved in 13 (pCR: 16,9%) of patients. The mean number of lymph nodes removed was 11. 51 patients (66,2%) started CT post-surgery. With a median follow up of 113 months [range 24-199],26 patient (33,8%) presented disease progression, 5 local and 21 distant recurrence. There were 14 deaths due to disease progression. 5-years OS was 87% (CI 95%: 79,4-94,6%) and DFS was 80,2 (CI 71-89,4%). Conclusions: Our data support the rutine use of CAPOX and following CRT prior to surgery on PT with PRRC, with promising results consistent with published trial data.
Treatment pattern and outcome of locally advanced rectal cancer in Tikur Anbessa Specialized Hospital (TASH), Addis Ababa, Ethiopia: An institution-based cross-sectional study.
Authors: Hailu Elias Amare , Woldetsadik Edom Seife , Tadesse Biruk Legesse , Kelemu Hedagewoin Friew , Zingeta Girum Tessema , Zewde Yonas Alemayehu , Aytehgeza Ruth , Dandena Abdi , Begna Kebede 
Published: June 2023

e15640 Background: The standard management of locally advanced rectal cancer (LARC) is neo-adjuvant concurrent chemo radiation (CCRT) followed by total meso-rectal excision. Recently there is an increased interest in total neo-adjuvant treatment (TNT). Most patients with rectal cancer in developing countries present in advanced stage for several reasons including lack of resources and delayed health seeking behavior. Most patients are not able to get standard management. This study tries to assess treatment patterns and outcomes in LARC. Methods: A cross-sectional study was conducted in patients with LARC that are treated at TASH from Jan 1, 2020 up to Sept. 2022. The data was collected from Patient’s cards using a pre-structured format that included demographic data, laboratory, pathological and imaging information. Data analysis was conducted by using IBM SPSS version 25. Results: 100 patients were included in the study, 51% were male. The median (range) age at diagnosis was 45.5 (20-86) years. 81% of patients came to our center without getting any oncologic treatment and 75.3% of them were presented on a multi-disciplinary tumor board for their treatment decision. Upfront surgery was decided in 48.1% (39/81) of patients. Standard neo-adjuvant treatment of either TNT or CCRT was decided in 23.4% (19/81) and 8.6% (7/81) of patients respectively. There is no significant association between tumor location, TNM stage, mesorectal fascia status and first treatment decision. Only 12 (14.8%) patients were able to finish their whole treatment plan. The most common reason for not finishing all treatment was prolonged radiation waiting time, with the median (range) waiting time of 10 ± 7.1 (1-26) months. From 81 treatment naive patients, 79 were decided to have surgery; and 59.5% (47/79) underwent the planned surgery with 89.9% R0 resection rate. R0 resection rate in patients who undergo upfront surgery was 91.2% (31/34). Neo-adjuvant chemotherapy was given to 34.6% (28/81); and only 18% (5/28) underwent subsequent surgery. The most common reason for not undergoing subsequent surgery was disease progression 43.5% (10/23) during or after finishing the neo-adjuvant chemotherapy. Only 24% of the study participants received radiotherapy. From the patients who took radiotherapy, only two patients received short course radiotherapy. Conclusions: Treatment decisions for rectal cancer in our study did not conform to standard treatment recommendations. Upfront surgery maybe a better option than neoadjuvant chemotherapy, since timely administration of standard neoadjuvant treatment is not possible. Alternative radiotherapy treatment options like short course radiotherapy may be better in resource limited setting to alleviate the longer radiotherapy waiting time.
Electronic frailty index to assess post-operative healthcare utilization in veterans with non-metastatic colon cancer.
Authors: Zhu Huili , Razjouyan Javad , Yarlagadda Sudha , Sada Yvonne H 
Published: June 2023

e15642 Background: Frailty is a measure of physiologic reserve and is associated with adverse perioperative outcomes in patients with cancer. Existing surgical frailty measures, such as the 11-factor and 5-factor modified frailty index, may not be routinely utilized due to time constraints. Electronic Frailty Index (EFI) serves as an efficient and automated alternative. There is limited data for the use of EFI in assessment of post-operative healthcare utilization in patients with non-metastatic colon cancer. Methods: We performed a retrospective cohort study using VA administrative files from 2016 -2020 and VA Central Cancer Registry. EFI was calculated based on the Veterans Affairs-FI (VA-FI), a validated 31-item cumulative deficit FI, to define three groups: robust (≤ 0.1), prefrail (0.1 - 0.2), and frail ( > 0.2). Cox proportional hazard analyses were conducted to evaluate survival. Logistic regression analyses were performed to examine healthcare utilization. All models were adjusted for age, gender, race, stage, and Charlson Comorbidity Index. Confidence intervals (CI) were calculated as 95%. Results: Among 2,861 patients (median age 70.7 ± 9.1 years) with stage I – III colon cancer who underwent surgery, 42.5% were robust, 36.6% were prefrail, and 20.8% were frail. The cohort was comprised of stage I (32.9%), stage II (34.9%), and stage III (32.2%) cases. Prefrail patients were at increased odds of emergency room (ER)/urgent care (UC) use at one year (adjusted odds ratio [aOR] 1.41, CI 1.09 – 1.83) compared to robust patients. Frail patients had an increased odds of ER/UC visits at 30 days (aOR 1.95, CI 1.19 - 3.20), 60 days (aOR 2.18, CI 1.42 - 3.34), and one year (aOR 2.79, CI 2.06 - 3.78). Increased risk of death was found in prefrail (adjusted hazard ratio [aHR] 1.34; CI 1.12 - 1.59) and frail (aHR 2.38; CI 1.97 - 2.86) patients when compared to robust patients. Conclusions: EFI was significantly associated with higher ER/UC utilization among frail patients with colon cancer who received curative intent surgery, independent of stage. Pre-frail and frail patients had worse survival outcomes compared to robust patients. Further work is needed to develop EFI as a risk-stratification tool in curative intent patients with colon cancer prior to surgery.
The impact of treatment adherence on overall survival in non-metastatic colorectal cancer in Latin American patients.
Authors: Namuche Fernando , Leon Jorge , Flores Claudio J. 
Published: June 2023

e15644 Background: Colorectal cancer is a significant public health issue in Peru, and non-metastatic colorectal cancer patients face numerous treatment challenges. Adherence to treatment protocols has been identified as an important factor influencing patient outcomes. However, little is known about the impact of treatment adherence on overall survival in non-metastatic colorectal cancer patients in Peru. The objective of this study is to investigate the association between treatment adherence and overall survival in this patient population. Methods: We retrospectively reviewed the electronic medical files of 890 patients with non metastatic colorectal cancer between 2006 and 2020. Patients were included if they received treatment and were followed up for at least two years. Treatment adherence was measured based on the number of completed chemotherapy cycles and the time to initiate treatment after surgery. Overall survival was defined as the time from diagnosis to death or the last follow-up visit. Multivariate analysis was performed to identify factors associated with overall survival. Results: A total of 890 patients were included in the study, and the median follow-up time was 32 months. The overall adherence rate was 71.7%. Patients who adhered to treatment had a significantly higher overall survival rate compared to non-adherent patients (p < 0.001). A multivariate analysis was performed using Cox regression model with the statistically significant variables found (sex, high histologic grade, stage and adherence to treatment) in the univariate analysis. Multivariate analysis showed that treatment adherence was an independent predictor of overall survival (HR = 0.69; 95% CI, 0.54-0.88; p < 0.001). Conclusions: Our findings indicate that medication adherence is a crucial factor affecting overall survival in Peruvian patients with non-metastatic colorectal cancer. Patients who adhered to treatment had a significantly higher overall survival rate than non-adherent patients, highlighting the importance of adherence in optimizing patient outcomes. These findings have important clinical implications for healthcare providers, who should prioritize efforts to improve treatment adherence in this patient population.
Real-world impact of time-to-treatment initiation and initial treatment modality on survival in pancreatic and colorectal cancers.
Authors: Schwanke Joshua , Patterson Brooke , Marmor Schelomo , White McKenzie Joy , Jensen Eric Hans , Tignanelli Christopher , Lou Emil , Prakash Ajay 
Published: June 2023

e15646 Background: Overall survival for patients with pancreatic ductal adenocarcinoma (PDAC) and colorectal cancers (CRC) has increased significantly over the past decade; however, the optimal time-to-treatment initiation (TTI) and initial treatment modality (ITM) have not been defined. These variables have likely been affected by increased adoption and changes in types of neoadjuvant treatment strategies for these cancer types. Thus, we performed a retrospective observational study of TTI and ITM in patients with CRC and PDAC within the MHealth/Fairview medical system. Methods: We identified 424 patients with stage I-III RC and 316 patients with stage I-III PDAC within the MHealth/Fairview system (Minneapolis, MN) from 2011-2021 with North American Association of Central Cancer Registries data enriched by the electronic health record. Patients were stratified by TTI from diagnoses as: 0-7 days, 8-14 days, 15-28 days, 29-42 days, and over 43 days. ITM, defined as initial chemotherapy/chemoradiation, surgery, or radiation, was analyzed independently for patients with rectal cancer (N = 267) and PDAC. Effect of TTI and ITM on overall survival was calculated using a Cox proportional Hazard (CPH) model controlling for clinical stage. Results: TTI was significantly associated with survival in CRC, with patients treated in 8-14 days and 15-28 days showing increased survival over patients treated in over 43 days (HR 0.397, p = 0.007 and HR 0.276 p < 0.001, respectively). There was no significant hazard for TTI and survival in PDAC. We also found that neoadjuvant chemotherapy/chemoradiation had a lower hazard for death in rectal cancer relative to upfront surgery (HR 0.323, p = 0.002), when controlling for stage. Surgery was significantly more likely to be correlated with stage I or II disease than chemotherapy/chemoradiation (68.5% vs 24.7%, p < 0.0001 by Spearman method). There was no significant association between ITM and survival in patients with PDAC. Conclusions: Early treatment for CRC is associated with improved survival in this population, implying that treatment delays decrease the efficacy of curative-intent therapy. Evaluation of treatment modality in the rectal sub-group showed improved outcomes with neoadjuvant chemotherapy and chemoradiation, despite upfront surgery being associated with lower stage. The lack of association between TTI and survival in PDAC is likely related to the relatively poor outcomes observed with this disease and highlights the need for better screening and treatment for resectable disease. These results are notable because they suggest that a thorough workup and appropriate therapy may be more important than rapid treatment.
Predicting treatment response for the safe non-operative management of patients with rectal cancer using an MRI-based deep-learning model.
Authors: Selby Heather M. , Liu Charles , Sheth Vipul , Napel Sandy , Wagner Todd , Morris Arden M. 
Published: June 2023

e15648 Background: Neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision (TME) surgery has been the standard treatment for patients with locally advanced rectal cancer. Surgery, while effective in treating rectal cancer, can lead to significant long-term morbidity, such as bowel, urinary, and sexual dysfunction, and potential dependence on a colostomy for evacuation. A pathologic complete response (pCR) to neoadjuvant CRT suggests that TME surgery may not be necessary, as the tumor may have been effectively treated with CRT alone. However, the only definitive determination of pCR is based on a pathologic exam, which requires a surgical specimen. By comparing pre- and post-CRT images, clinical complete response (cCR) is a surrogate for pCR that does not require surgery. However, cCR is a poor proxy for pCR, with sensitivity and positive predictive values of 34.1% and 30.6% respectively1. Purpose: Our aim is to develop a multiparametric longitudinal MRI-based 3D deep-learning model to predict pCR in patients with locally advanced rectal cancer. Methods: We identified 360 patients with rectal cancer who had neoadjuvant CRT followed by surgical resection between January 2012 and December 2021 in an academic medical center. We have classified patients into two groups based on the presence or absence of pCR in their resected tumor specimen. We will train and validate a multiparametric longitudinal MRI-based 3D deep-learning model to predict pCR. Our model will use T1-weighted, T2-weighted with and without contrast, and/or diffusion-weighted MRIs before and after neoadjuvant CRT to predict pCR. Using multiparametric MRIs offers a comprehensive understanding of the tumor and surrounding tissue, and including longitudinal MRIs will provide valuable information on the impact of treatment. To assess the performance of the model, we will use receiver operating characteristic (ROC) analysis as well as positive and negative predictive values to evaluate its ability to predict pCR. Preliminary Results: Among 360 patients, 227 (63.1%) were male, 187 (51.9%) were Non-White, and the average age was 58.7 (SD of 13.3) years. The surgical pathology reports showed that 44 (12.2%) patients had achieved a pCR, while the visual assessment of post-CRT MRIs revealed that 49 (13.6%) had achieved a cCR. 1. Liu, C. et al. Predictive Value of Clinical Complete Response after Chemoradiation for Rectal Cancer. J. Am. Coll. Surg. 235, S51–S52 (2022).