bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex difference in tolerability of adjuvant oxaliplatin-based chemotherapy for colorectal cancer and changes in diagnostic components of sarcopenia: A prospective study.
Authors: Nozawa Hiroaki , Abe Shinya , Abe Kentaro , Yokota Yumi , Yakabe Mitsutaka , Akishita Masahiro , Ishihara Soichiro 
Published: June 2023

e15625 Background: We previously reported that based on CT images at the 3rd lumbar vertebra, female patients with colorectal cancer (CRC) were more likely to be sarcopenic than male patients after curative resection, and predisposed to develop early dose limiting toxicities (DLTs) in adjuvant CAPOX therapy. Although oxaliplatin-based adjuvant chemotherapy for CRC is prevalently used worldwide, it is largely unknown how the treatment affects patients in terms of sarcopenia. Therefore we conducted a prospectively study on the impact of adjuvant chemotherapy on multifactorial components assessed for sarcopenia. Methods: We examined stage II-III CRC patients who received adjuvant CAPOX after curative surgery after March 2022. Informed consent was obtained from all participants. During this systemic therapy, we assessed nutritional status using Mini-Nutritional Assessment (MNA, an 18-item questionnaire consisting of psychological well-being, diet quality, physical activity and anthropometric metrics; score range:0-30), and examined gait speed and grip strength, as well as whole body skeletal muscle mass, fat mass, and bone mineral using a body composition analyzer. The changes in these metrics were analyzed in association with dose reduction/adverse events of CAPOX. All continuous variables were tested by Wilcoxon rank-sum test. Results: Eighteen men and 13 women (mean age: 61 years old) were included in this study. Seven (39%) male and seven (54%) female patients required dose reduction within the four treatment cycles (p = 0.65). The median MNA, gait speed, grip, muscle mass, fat mass and bone mineral at the first and fourth cycles of CAPOX in men were 20.4 and 24.0, 1.10 and 1.23 m/sec, 30.9 and 31.2 kg, 27.3 and 28.0 kg, 11.8 and 11.9 kg, and 2.8 and 2.9 kg, respectively. The median of these metrics at the first and fourth cycles of CAPOX in women were 21.4 and 22.4, 1.32 and 1.33 m/sec, 22.0 and 22.4 kg, 21.95 and 22.12 kg, 13.43 and 14.62 kg, and 2.34 and 2.31 kg, respectively. The relative values (medians) of the metrics at the fourth cycle to those at the first cycle of CAPOX (men vs women) were as follows; MNA:1.131 vs 1.045 (p = 0.057), gait speed:1.075 vs 0.950 (p = 0.17), grip:1.018 vs 1.044 (p = 0.81), muscle mass:1.028 vs 1.011 (p = 0.036), fat mass:1.029 vs 1.080 (p = 0.47), and bone mineral:1.030 vs 0.991 (p = 0.015). Conclusions: It is suggested that adjuvant CAPOX has negative impact on postoperative recovery of psychological and physical components in female patients.
Immune checkpoint inhibition in locally advanced rectal adenocarcinoma at Mayo Clinic.
Authors: Imperial Robin John Lester , Alomari Mohammad , Elawady Mohamed , Jones Jeremy Clifton , DeLeon Michelle 
Published: June 2023

e15626 Background: Studies have shown the effectiveness of immune checkpoint inhibition (ICI) in patients with tumors demonstrating microsatellite instability (MSI-H) and an associated defect in DNA mismatch repair (dMMR). In particular, KEYNOTE-177 demonstrated significant survival benefit for patients with unresectable or metastatic colorectal cancer with MSI-H or dMMR. Recently published case reports and series have demonstrated similar outcomes for patients with locally advanced and resectable rectal cancer. We report on the experience of patients with locally advanced, resectable rectal adenocarcinoma treated across the Mayo Clinic Health System. Methods: We conducted a retrospective analysis of patients treated at Mayo Clinic since 2015 A search of the Mayo Clinic database was done to include parameters for confirmed rectal adenocarcinoma, dMMR in pathology reports. Patients receiving ICI treatment including pembrolizumab, nivolumab/ipilimumab and durvalumab in any combination with chemotherapy and/or radiation were included. Patients with metastatic disease at the time of surgical intervention or ICI were excluded. Clinical data was assimilated. Results: Twenty-one patients met criteria for inclusion in our analysis. Fifteen patients had de novo disease. Six patients had local recurrence and had been treated previously with chemotherapy, radiation (RT) and surgery. None of the patients included had prior ICI therapy. Fifteen patients had Lynch syndrome. The median age of diagnosis was 41.5 years. Seven patients underwent surgical intervention. of the seven patients received surgery upfront followed by immunotherapy. The remaining six had neoadjuvant immunotherapy alone or in combination with chemotherapy and/or radiation. Prior to surgery, all patients demonstrated radiographic partial response (rPR). 67% of these demonstrated a pathologic complete response (pCR) while 33% had residual disease. The patient who received surgery upfront and adjuvant ICI continues to have radiographic stable disease after 1 year of treatment. For patients who did not have surgery, 50% had radiographic “complete or near complete” response (rCR), 43% had rPR and 7% had radiographic stable disease. Ten patients received RT and ICI with 70% demonstrating rCR and 30% rPR. Overall, the objective response rate was 90 Response to treatment was observed upwards of 75 months. Only 1 person in the study had progression of disease that occurred after 14 months of therapy. Conclusions: Similar to KEYNOTE-177, patients with locally advanced MSI-H/dMMR rectal cancer have significant and durable response to immunotherapy alone or in combination with chemotherapy, radiation and surgery. Further large prospective trials are needed to validate these findings and determine a standardized approach.
Early colorectal cancer detection with a spectroscopic liquid biopsy.
Authors: Cameron James Munro , Antoniou Georgios , Brennan Paul , Conn Justin , Gray Ewan , King Sharon , McHardy Rose , Moug Susan , Nobes Jennifer , Palmer David , Sala Alexandra , Smith Benjamin , Strachan Judith , Mowat Craig , Baker Matthew 
Published: June 2023

e15627 Background: Earlier diagnosis and treatment of colorectal cancer (CRC) maximizes the opportunity to combat or control disease progression. The average 5-year survival rate after diagnosis decreases from 91% in early-stage CRC, to as low as 15% for stage IV CRC. Furthermore, rapid detection and removal of pre-cancerous adenomas – e.g., advanced adenomas (AA) – can significantly improve survival rates of affected patients. However, current stool-based tests have inadequate AA sensitivities, such as FIT (24%) and FIT-DNA (42%). Liquid biopsies have great potential to supplement FIT tests and improve diagnostic pathways, but current blood tests based on tumor-derived biomarkers also have limited sensitivity for AA detection. Methods: The Dxcover® Cancer Liquid Biopsy is based on Fourier-transform infrared (FTIR) spectroscopy applied to serum from a standard blood sample. The spectral data are collected and analyzed using pattern recognition and machine learning algorithms to detect disease-specific signatures. We initially examined test performance for the detection of multiple cancer types. Additionally, we have analyzed a retrospective cohort of samples comprising 100 CRC, 99 AA removed by surgical resection and 97 colonoscopy screening controls. Results: The CRC classifier from the discovery multi-cancer dataset resulted in 74% sensitivity with 91% specificity when differentiating CRC and non-cancer, which surpasses the targets set by the Centers for Medicare & Medicaid Services (CMS) for coverage of CRC tests. Receiver operating characteristic (ROC) analysis reported an area under the curve (AUC) value of 0.91. The machine learning algorithms can be fine-tuned to maximize either sensitivity or specificity depending on the requirements of different patient pathways. When tuned for higher sensitivity, the model produced 97% sensitivity (49% specificity), and when tailored for greater specificity (97%) the sensitivity was 47%. We have now progressed these findings to examine the ability of the technology to differentiate patients with CRC, AA and colonoscopy controls. Furthermore, we assess whether combining spectral data with additional clinical information, such as biomarker data and patient demographics, can enhance test performance. Conclusions: A rapid blood test that is sensitive to AA and early-stage CRC could improve patient prognosis and reduce cancer burden. With further development, this liquid biopsy could have a profound impact on the earlier detection of CRC.
Adjuvant chemotherapy in ypStage III locally advanced rectal cancer after neoadjuvant treatment with an oxaliplatin-based regimen.
Authors: Cai Runkai , Zhang Jianwei , Cai Yue , Wu Zehua , Hu Huabin , Xie Xiaoyu , Deng Yanhong , Cheng Yi , Zhang Yuting 
Published: June 2023

e15628 Background: Fluorouracil -based neoadjuvant chemoradiotherapy(CRT) followed by total mesorectal excision and adjuvant chemotherapy is the standard treatment for locally advanced rectal cancer (LARC). Adjvuant FOLFOX improved survival benefit compared with fluorouracil in patients with ypStage II andIII after CRT. However, induction or consolidation chemotherapy with FOLFOX before surgery had been the new standard for LARC. Whether adjuvant chemotherapy with FOLFOX still improves survival outcomes in ypStage III patients previously exposed to oxaliplatin-based treatment was unknwon. Methods: Patients with LARC receiving oxaliplatin-based neoadjuvant treatment from January 2015 to December 2019 were retrospective analyzed. The inclusion criteria included neoadjuvant FOLFOX chemotherapy alone or induction chemotherpay, concurrent FOLFOX and consolidation chemotherapy before CRT. The duration of neoadjuvant oxaliplatin exposure time was less than 4 months. The efficacy of adjvuant FOLFOX chemotherapy was analyzed among these ypStage III patients according to adjuvant chemotherapy cycles after surgery. Results: A total of 227 patients with ypStage III were enrolled, with the 3-year DFS rate of 46.1% (95%Cl 37.3%-54.9%).Among these patients, 193 patients received adjuvant FOLFOX chemotherapy, including 7 patients had ≤ 2 cycles of adjuvant treatment. And 34 patients had observation after surgery. The 3-year DFS rates bewteen FOXFOL adjvuant chemotherapy group and observation group were 44.7% vs. 56.5%, respectively (HR, 1.190, 95%Cl 0.6246-2.267, P = 0.597). Forty-one patients had ≤ 2 cycles of adjuvant treatment. The 3-year DFS was 43.6% vs. 60.4% (P = 0.597) between pateints receiving over 2 cycles of adjvuant chemotherapy and ≤ 2 cycles of treatment. Conclusions: Among ypStage III LARC pateints after neoadjuvant treatment with Oxaliplatin-Based regimen, adjuvant chemotherapy with FOLFOX failed to improved surival benefit. More enhanced regimen might be necessary for these oxalipatin-resistant patients.
Circulating tumor DNA detection as a prognostic tool in patients with localized colon cancer: A systematic review and meta-analysis.
Authors: Do Quan , Katiyar Vatsala , Malloy Meghan , Sharma Vivek R. 
Published: June 2023

e15629 Background: Current modalities for postoperative risk stratification in localized colon cancer are still suboptimal in guiding adjuvant chemotherapy (ACT) administration. In recent years, circulating tumor DNA (ctDNA) has emerged as a novel biomarker to identify patients at high-risk for recurrence following R0 tumor resection. In this meta-analysis, we aimed to assess the prognostic value of ctDNA detection on postoperative recurrence risk that in the future, with further study, may help guide ACT treatment. Methods: Electronic databases Pubmed, Google Scholar, and Embase were searched up to 31 January 2023. Patient data were extracted using the following inclusion criteria: stage I to III colon cancers, R0 resection, sufficient ctDNA data following surgery, and no other concurrent malignancy. Pooled relative risk (RR) and 95% confidence interval (CI) were estimated to assess ctDNA positivity on the risk of recurrence in patients having surgery only, patients having surgery followed by ACT, and all patients combined. Random effects model was implemented to account for inter-study variation. Study heterogeneity was detected using χ2 test and I2 coefficient, with I2 more than 50% indicating significant heterogeneity. All analyses were completed using RevMan 5, with p < 0.05 being statistically significance. Results: Fifteen studies with a total of 3411 patients (64.4±10.7 years old) were evaluated. In patients undergoing surgery only without ACT treatment, postoperative ctDNA-positive patients were at higher risk of recurrence compared to those with negative ctDNA (RR = 7.73, 95% CI: 5.73-10.42, p < 0.01, I2= 0%). In patients having surgery followed by ACT, postoperative/pre-ACT ctDNA-positive patients were at higher risk of recurrence compared to ctDNA-negative ones (RR = 5.25, 95% CI: 3.67-7.50, p < 0.01, I2= 19%); post-ACT ctDNA-positive patients were also at higher risk of recurrence (RR = 6.34, 95% CI: 4.12-9.78, p < 0.01, I2= 29%). When combining the two populations (surgery only and surgery followed by ACT), postoperative ctDNA-positive patients again have higher risk of recurrence (RR = 3.86, 95% CI: 2.63-5.67, p < 0.01, I2= 87%); after completing all treatments, ctDNA-positive patients continue to have higher risk of recurrence (RR = 7.02, 95% CI: 3.40-14.51, p < 0.01, I2= 94%). Conclusions: This meta-analysis shows that the presence of ctDNA post-surgery correlates with higher risk of disease recurrence. In localized colon cancers, ctDNA detection can be a valuable tool to identify high-risk patients who, regardless of pathologic stage, may be the most likely to benefit from ACT treatment. Additionally, patients with persistently positive ctDNA after completing ACT are at very high risk for recurrence and should require closer follow-up than current guidelines, along with consideration of enrollment in clinical trials of newer treatment strategies.
Immunotherapy in locally advanced and metastatic rectal 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

e15633 Background: Immunotherapy has been increasingly used in cancer therapy. In rectal cancer, patients with high microsatellite instability (H-MSI) are candidates for immunotherapy, but there is little evidence on its effect on overall survival. Methods: A retrospective analysis of all patients with stage II-IV rectal adenocarcinoma in the US National Cancer Database (NCDB) between 2010 and 2019 was performed. Patients without data on whether or not they had immunotherapy were excluded. Propensity-score matching was used to adjust for baseline and treatment confounders and the cohort was divided into two groups: patients who received immunotherapy and matched controls. The primary outcome was overall survival. Secondary outcomes included 30-day readmission and 30- and 90-day postoperative mortality. Results: 5175/206,615 (2.5%) patients with rectal adenocarcinoma were treated with immunotherapy during the study period. Patients treated with immunotherapy were younger (58 vs 62 years; p < 0.001), more often male (64.4% vs 61.7%; p < 0.001) and had more private insurance (50.8% vs 43.4; p < 0.001) compared to controls. Patients treated with immunotherapy had more metastatic disease at presentation (clinical TNM Stage IV - 80.8% vs 23.3%; p < 0.001), presented with larger tumors (median: 5 vs. 4.2 cm; p < 0.001) and less often underwent surgery (33.7% vs. 69.9%; p < 0.001), radiation therapy (21.5% vs 57.4%; p < 0.001) and standard chemotherapy (38.1% vs 61%; p < 0.001). After matching, 488 patients were included in each group. Overall survival was significantly shorter in the immunotherapy group, with a mean survival of 56.4 months (95%CI – 53.03-59.86) compared to 70.5 months (95%CI – 66.15-74.92) in the control group (p = 0.004). Cox regression analysis of factors associated with overall survival demonstrated that, for the entire cohort, immunotherapy was associated with an increased mortality (HR 2.16; 95%CI: 2.09-2.24; p < 0.001). After stratifying based on clinical staging, immunotherapy was associated with improved overall survival in stage IV patients (HR 0.91, 95%CI 0.88-0.95; p < 0.001) but with lower survival in stage II (HR 2.38; 95%CI: 2.05-2.77; p < 0.001) and stage III (HR 2.43; 95%CI: 2.18-2.7; p < 0.001). Conclusions: Immunotherapy was associated with a modest increase in overall survival in patients with stage IV metastatic rectal cancer. However, overall survival was significantly lower in patients with Stage II-III disease when treated with immunotherapy.
A new approach to reduce toxicity and improve quality of life in colon cancer patients receiving adjuvant chemotherapy.
Authors: Orlova Rashida , Varankina Anna , Androsova Alexandra , Belyak Natalia P. , Kutukova Svetlana 
Published: June 2023

e15649 Background: We investigated the possibility of using accompanying therapy with enterosorbent in CRC patients receiving adjuvant chemotherapy. Methods: 40 pts (62 years [54.0-68.5]) with CRC (II-III) after radical surgery were randomized in 2 groups (1:1). Patients in the group 1 received ACT (XELOX), patients in group 2 received XELOX and enterosorbent "Polysorb" 30 mg orally, daily from 16 to 20 days of the ACT cycle. Results: The use of an enterosorbent can significantly reduce the manifestations of gastrointestinal toxicity: vomiting (5.0% vs 35.0%; p = 0.018), diarrhoea (5.0% vs. 40.0%; p = 0.008), flatulence ( 25.0% vs 70.0%; p = 0.004), constipation (0 vs 20.0%; p = 0.035) and abdominal pain (15.0% vs 50.0%; p = 0.018). In group 2, already by the 2nd cycle, the median scores on the QLQ-C30 symptomatology scale amounted to 22.0 points [14.0-28.5] vs 29.9 points [23.0-33.0] in the control group (p = 0.0441). By the 3 cycle in group 2, the average score on the QLQ-C29 symptomatic scale was 13.0±5.2 points (95% CI 10.5-15.4) and was significantly lower than in the control group (18.0±7.8 points (95% CI 14.3-21.6); p = 0.0224). When assessing the general condition according to the results of the analysis of the QLQ-C30 questionnaire, in the control group of patients there was a significant decrease in the number of points already by the beginning of the 2nd cycle of ACT - before the start of cycle 2 of ACT(p = 0.0369) and cycle 4 of ACT (p = 0.0447). Score of EQ-5D in the control group, significant decreases before 2 (from 84.9±6.4 points (95% CI 81.9-87.9) to 80.5 [77.55-86, 5]) (p = 0.0477) and 3 cycle ACT (from 80.5 [77.55-86.5] to 77.0±4.7 (95% CI 74.7-79.2)) (p = 0.0170), as well as a decrease in patient satisfaction with their condition at the time of the start of the 4th cycle of ACT compared with the baseline visit from 84.9±6.4 points (95% CI 81.9-87.9) to 75.7 ±6.7 points (95% CI 72.3-79.0) (p = 0.0001). Conclusions: The use of an enterosorbent as an accompanying therapy in CRC patients receiving ACT can significantly reduce the manifestation of chemotherapy toxicity and improve the quality of life of patients.
The adjuvant oxaliplatin-irinotecan paradox.
Authors: Mackey James David , Young Peter , Preble Richard , Miles Brittany 
Published: June 2023

e15655 Background: A pervasive pattern in oncology is that chemotherapeutic agents which achieve acceptance for adjuvant use are the ones that have shown superior efficacy in the treatment of metastatic disease. The greater the efficacy in metastatic disease, the greater the likelihood that adjuvant use will be statistically viable. Oxaliplatin is the exception to this, having paradoxically shown similar outcomes to irinotecan in metastatic colorectal cancer (CRC) but superiority in the adjuvant setting. In this study, the TriNetX research database was used to better evaluate the adjuvant efficacy of oxaliplatin use in real-world patients. Methods: The TriNetX research database was used for this study. The TriNetX platform provides access to anonymized medical record information on more than 91 million patients in 75 large healthcare organizations. Three cohorts of stage III colorectal patients were created for comparison, utilizing International Classification of Disease-10 (ICD-10) codes and medication codes provided in the TriNetX platform. All patients were required to have a diagnosis of colon cancer (C18) and lymph node involvement (C77), with the absence of any liver or lung metastases (C78.7 and C78.0, respectively). Adjuvant oxaliplatin use was identified by the presence of the oxaliplatin medication code within 9 months of CRC diagnosis. The adjuvant oxaliplatin cohort was compared to a cohort with no oxaliplatin exposure, identified by the exclusion of the oxaliplatin medication code for 12 months following CRC diagnosis. The cohorts were balanced for age, race, gender, and ethnicity. The endpoint of the comparisons was all-cause mortality at 5 years. Results: Adjuvant use of oxaliplatin was associated with a 2.3% absolute decrease in the risk of death at 5 years (risk ratio 0.88, 95% CI (0.79,0.97), p-value 0.01). See figure 1. Conclusions: This study shows that adjuvant use of oxaliplatin is associated with a 2.3% absolute survival advantage in stage III colorectal cancer patients. This small absolute benefit is likely why occasional retrospective analyses have been unable to replicate it. A controlled interrupted time series analysis from Huang, et. al. showed no benefit to adjuvant oxaliplatin in the stage III setting for Taiwanese patients. Such a small benefit may also explain why the ACHIEVE trial found three months of adjuvant oxaliplatin to be equivalent to six. When a benefit is very small, a shorter duration of treatment would be more likely to result in statistical equivalency than if the benefit was more substantial. [Table: see text]