bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumour radiomics as imaging biomarker of tumour response to chemo-radiotherapy in patients with adenocarcinoma of rectum.
Authors: Engineer Reena , Puppalwar Abhinav , Sastri Jayant , Jha Ashish , Kumar Suman , Saklani Avanish 
Published: January 2023

243 Background: We aimed to study whether texture (Radiomic) features obtained from T2W MRI of patients with rectal cancer can be used as a surrogate imaging biomarker to predict response to NACTRT. We explored various machine learning tools to develop the best model to predict response to NACTRT. Methods: One hundred patients with stage II/III who underwent MRI before and after NACTRT and surgical treatment were enrolled. Patients were classified into complete response (pCR, n = 21) and partial and nonresponse (pPR + pNR, n = 53) on the basis of histopathological report (74 patients who underwent surgery) and clinico-radiological response (26 patients who did not undergo surgery). Tumor volumes (Region of interest) were manually selected in each tumour segment. There were sixty four first-order and higher-order radiomic features. Recursive feature elimination method was used for feature selection and 5 prediction models were tested using 10-fold cross validation for predicting tumour response to NACTRT. Results: Using prediction model assessment matrix (RFC, SVC, GBC, NBC, ABC), the best results for prediction response were obtained using the random forest model with AUC of 0.79 ± 0.15 (Mean ± Standard deviation) accuracy of 0.72 ±0.12, precision of 0.77 ± 0.10, sensitivity of 0.87 ± 0.07, f1 score- 0.81 ±0.07. By using random forest model, Texrad features obtained from pre and post NACTRT MRI could accurately predict pCR. To the best of our knowledge, apart for the added values of RF model to Texrad features, is the first study to demonstrate and compare RF, SVC, GBC, NBC, Adaboost models to the same cohort of patient with 10-fold validation. Conclusions: Our study shows that RFM was most accurate and stable for predicting tumour response. MRI based Radiomic features can be used as surrogate image biomarker to accurately predict the treatment response to NACTRT in patients with locally advanced rectal cancer. The prediction model can be used as a complementary non-invasive tool to identify patients eligible for organ preservation. [Table: see text]
Genomic analysis to elucidate similarities and differences between primary colorectal cancers and colorectal cancer liver metastases.
Authors: Buechler Steven Allen 
Published: January 2023

25 Background: Whole transcriptome (WT) analysis of primary colorectal cancer (pCRC) has shown that the tumor microenvironment (TME) plays a critical role in disease progression and response to treatment. Colorectal cancer liver metastases (CRCLM) bear many genetic similarities to primary tumors, however differences in the microenvironment could effect drug response. Since 80% of metastatic CRC patients have liver metastases there is a critical need for further molecular analysis of CRCLM. Methods: Using a novel method to identify aberrant activity of signaling pathways, continuous scores (called pathway cluster scores, PCS) were derived from subsets of Hallmark gene sets of MSigDB. PCS scores that were prognostic in CRCLM were considered relevant to disease progression. Combined studies of such scores in CRCLM and pCRC were used to explore differing effects of the colon and liver TMEs. Analyses were performed on published WT datasets of pCRC (4 cohorts, n = 2,978) and CRCLM (3 cohorts, n = 498). Immune cell infiltration levels were estimated with Immunedeconv. Results: The most significantly prognostic PCS score in CRCLM cohort GSE159216 (n = 171) was one derived from a cluster of 28 KRAS signaling genes, called K-score (p = .0004). Subtypes K+ (good prognosis) and K- (poor prognosis) denote samples with K-score above, respectively below, the median. Gene set enrichment analysis showed that in all CRCLM cohorts, K- was enriched versus (v) K+ in proliferation-related pathways, e.g. E2F signaling and DNA Repair, while K+ was enriched v K- in multiple immune system pathways. In both CRCLM cohorts, K+ was enriched v K- in infiltration of neutrophils and CD4+ T cells, while infiltration levels of CD8+ T cell were not significantly different between K+ and K-. The T cell homing chemokines CXCL12, CCL19, CCL21 were elevated in K+ v K-. The aforementioned molecular features of K+ and K- also held in all pCRC cohorts; however in these cohorts, K+ was also enriched v K- in B cell and M2 macrophage infiltration. Also, in pCRC expression of the B cell attractor CXCL13 and biomarkers for tertiary lymphoid structures (TLS) were significantly elevated in K+ v K-. Of note, TLS have been associated with response to immune checkpoint inhibitors in multiple cancer types. In addition, in 18 pairs of matching pCRC and CRCLM samples (GSE49355), K-scores of pCRC samples were significantly correlated to K-scores of the matching CRCLM samples (p = .01). Chemokine expression levels differed in matching pairs: mean expression of CXCL12 was significantly higher in CRCLM than pCRC, while mean expression of CXCL13 was significantly higher in pCRC than CRCLM. Conclusions: In the study cohorts, K- tumors in both pCRC and CRCLM, were proliferative and lacked inflammation. However, while both pCRC and CRCLM K+ tumors were inflamed and enriched with CD4+ T cells, only pCRC K+ tumors were likely to contain TLS.
A multicenter, case-control study of a novel multi-target fecal DNA test for colorectal cancer detection.
Authors: Peng Jiaxi , Yin Meichen , Jiang Ruijingfang , Li Zhilong , Zhuo Duan , Qu Hongyue , Luo Mengxue , Liu Qian , Jiang Weijia , Sun Jianlong , Lin Jia , Wang Yuying 
Published: January 2023

26 Background: Globally, colorectal cancer (CRC) is the fourth most frequently occurring cancer and is the second leading cause of cancer-related deaths. Early detection and diagnosis of pre-cancer lesions and CRCs at curable stages could prevent the disease or improve patient survival. Colonoscopy, the current gold-standard approach for CRC screening, is an invasive procedure, and novel non-invasive alternatives are needed. Methods: In present study, we developed a novel multi-target fecal DNA based assay, which integrates detection of two stool DNA (sDNA) methylation markers by quantitative methylation-specific PCR (qMSP) and immunochemical fecal occult blood test. We performed a multi-center case-control study to validate the diagnostic performance of this novel multi-target assay. Thus far, we collected stool specimens from a total of 784 subjects including CRC, advanced adenoma, nonadvanced neoplasms and individuals with negative findings on colonoscopy from six sites across China. All participants underwent colonoscopy; the stool specimens were tested with the multi-target fecal DNA test as well as a quantitative FIT test (OC FIT-CHEK, Eiken) in parallel in order to perform head-to-head comparison of the test performance of both assays. Results: The multi-target fecal DNA test demonstrated a higher sensitivity (96.1%) than FIT (85.3%) for CRCs (n=204). Meanwhile, 20 of 39 (51.3%) patients with advanced adenoma tested positive by the fecal DNA test, which was remarkably superior to FIT (7 of 39 tested positive, 17.9%). Among 541 participants with nonadvanced neoplasms or negative findings on colonoscopy, the specificity of the DNA test was 86.9%, compared with a specificity of 93.1% achieved by FIT. Within the control group, the DNA test and FIT yielded a specificity of 90.5% and 94.9% respectively for individuals with negative results on colonoscopy. Conclusions: The novel multi-target fecal DNA test exhibited notably superior sensitivity for both CRC and advanced adenoma cases than the commercially quantitative FIT test, while sacrificing some specificity. Our results suggest that this novel multi-target fecal based test may be used as an effective tool for early detection and pre-screening of CRC. Prospective study will be conducted to further evaluate the clinical performance and cost-effectiveness of this assay.
Differences in genomic profiles of gastric adenocarcinoma in the US and Japan.
Authors: Nakauchi Masaya , Court Colin , Walsh Henry S. , Chatila Walid Khaled , Shimada Shoji , Vardhana Santosha , Tang Laura H. , Coit Daniel G. , Janjigian Yelena Y. , Maron Steven Brad , Ku Geoffrey Yuyat , Ilson David H. , Schultz Nikolaus , Matsuoka Hiroshi , Tsukamoto Tetsuya , Uyama Ichiro , Susa Koichi , Strong Vivian E. 
Published: January 2023

299 Background: Although epidemiological and clinical differences in gastric cancer (GC) between the US and Japan have been reported, genetic differences have not been clarified. We aimed to characterize molecular differences in GC between the two countries. Methods: We collected data between January 2010 and December 2019 from a prospectively maintained database of GC at our US and Japanese centers. After matching clinicopathological backgrounds, including age, sex, clinical T and N status, and tumor location, the genomic profiles of the primary site were compared for 58 patients in each group undergoing surgical resection and had MSK-IMPACT (MSK-Integrated Mutation Profiling of Actionable Cancer Targets), a tumor-normal next generation sequencing assay that can detect alterations in exons and select introns of 505 genes. The MSI sensor algorithm was used to assess microsatellite instability. Genomic alterations were filtered for driver variants using OncoKB, and genes were consolidated into pathways using curated pathway templates from the Cancer Genome Atlas. Results: The clinicopathological characteristics were well matched between 58 patients in each cohort. In the entire cohort, the most commonly altered genes were: TP53 (45%), ARID1A (24%), and ERBB2 (17%) in the US cohort, and TP53 (50%), ARID1A (19%), and ERBB2 (17%) in the Japanese cohort. Although KMT2D was more frequently altered in the US cohort (19% vs. 2%), the two cohorts had no significant differences in other altered genes and gene pathways. The tumor with MSI high was found more frequently in the US cohort (22.4% vs. 5.2%, p = 0.01). Among the MSI-normal tumors, the tumor mutational burden (US: 3.5 muts/Mb and Japanese: 4.1 muts/Mb) and the fraction genome altered (US: 0.37 and Japanese: 0.28) did not significantly differ between the two groups. Additionally, no genes or pathways were significantly enriched in either group. Patterns of mutual exclusivity and co-occurrence amongst genes and pathways were also similar between the two groups. Conclusions: In this original genomic comparison of US and Japanese gastric cancers, matching clinicopathological backgrounds, Japanese and US gastric cancers are remarkably similar at the genomic level, with the possible exception of MSI-high tumor that appear to be more frequent in the US.
Agreement between FGFR2 immunohistochemistry assays and fluorescence in situ hybridization (FISH) in metastatic gastric cancer: A comparison study.
Authors: Raskin Grigory A. , Mukhina Marina S. , Kravtsova Elena D. , Tjulandin Sergei , Tsimafeyeu Ilya 
Published: January 2023

301 Background: FGFR2 status of a patient with metastatic gastric adenocarcinoma could be an important factor in determining optimal treatment strategy with FGFR2 inhibitors and antibodies. The question remains how well different assays agree on the FGFR2 status of the same patient and whether one test can be substituted by another. Methods: Pairwise comparison of 4 tests based on the same patient population was performed: 3 IHC assays [Abcam clone EPR24075-418, R&D clone 98706, Santa Cruz clone C-8] and one FISH test. One hundred and nine formalin-fixed, paraffin embedded samples (including 64 primary tumors and 45 metastases of same patients) were obtained and were stained with FGFR2 IHC assays. Two trained pathologists independently evaluated the percentages of tumor staining and their intensity. FGFR2 FISH was performed as described previously [Su, BJC 2014]. The concordance analysis was performed to assess (1) correlation of FGFR2 expression/amplification between different assays in primary and metastases, (2) the predictive properties of one test of another. Results: After evaluating the expression in the first 19 patients, further study was carried out only using the Abсam assay due to pronounced nuclear staining with other IHC tests. FGFR2 any level expression was detected in 29 (47%) primary tumors and 18 (40%) metastases with concordance of 91%. The prevalence of FGFR2 amplification was 9.4% and intratumoral heterogeneity was observed in 33% of FGFR2 amplified cases. Pearson Correlation Coefficients (PCC) were: 0.89, 0.38 and 0.35 between IHC3+/FISH, IHC≥1% stained cells/FISH and IHC≥10%/FISH, respectively. The table represents how well one assay can predict the same outcome (positivity or negativity) of another assay. Conclusions: Among patients who were negative by FISH, 86%-93% of the patients were negative by IHC assay (Abcam). Among patients who were positive by FISH, 75-80% of them were positive by IHC. FISH should not be recommended as a substitute for a FGFR2 IHC assay due to high probability of false negative prediction as a result of intratumoral heterogeneity and low PCC. [Table: see text]
Adjuvant chemotherapy for older patients with stage II/III gastric cancer: A retrospective cohort study.
Authors: Shih Yu-Hsuan , Lin Hsin-Chen , Hsu Chiann-Yi 
Published: January 2023

303 Background: Current clinical guidelines recommended adjuvant chemotherapy for stage II and stage III gastric cancer after operation. The older patients were underrepresented in clinical trials and the role of adjuvant chemotherapy for older patients is unclear. We aimed to investigate the benefit of adjuvant chemotherapy in older patients with stage II and stage III gastric cancer. Methods: We retrospectively reviewed the medical records of patients with stage II-III gastric adenocarcinoma and underwent curative surgery at Taichung Veterans General Hospital (Taichung, Taiwan) between January 2009 and June 2017. The clinical characteristics and outcomes of patients ≥70-year-old were compared between patients received adjuvant chemotherapy or not received adjuvant chemotherapy. Results: A total of 357 patients were analyzed and 164 patients were older or equal to 70 years old. Majority of the young patients received adjuvant chemotherapy but only two-thirds of the old patients received adjuvant chemotherapy (93.8% vs. 61%; P<0.001). Among older patients, receipt of adjuvant chemotherapy was associated with longer disease-free survival (DFS) (10-year DFS, 45.89% vs. 17.55%; P<0.001) and overall survival (OS) (10-year OS, 61.71% vs. 36.27%; P=0.023) compared with patients who did not receive adjuvant chemotherapy. The total gastrectomy (hazard ratio (HR): 2.26; P=0.015), more advanced stage (HR: 2.71; P=0.018), positive surgical margin (HR: 2.56; P=0.02), elevated baseline carcinoembryonic antigen (HR: 2.37; P=0.026) were independent prognostic factors for OS in patients ≥70-year-old. Notably, the benefit adjuvant chemotherapy in older patients was significant in univariate analysis (HR: 0.53; P=0.025) but was not confirmed in multivariate analysis (HR: 0.52; P=0.072). Conclusions: The benefit of adjuvant chemotherapy in older patients with stage II-III gastric cancer was controversial in this retrospective study. Further prospective studies are needed to investigate this issue.
Real-world representativeness of patient-reported outcome measures of patients with esophagogastric cancer.
Authors: Kuijper Steven C. , Besseling Joost , Klausch Thomas , Slingerland Marije , van der Zijden Charlène , Kouwenhoven Ewout , Beerepoot Laurens V. , Haj Mohammad Nadia , Klarenbeek Bastiaan , Verhoeven Rob , Van Laarhoven Hanneke W.M. 
Published: January 2023

319 Background: The use of patient reported outcome measures (PROMs) is a popular method to obtain real-world patient data in oncological research. However, PROMs rely on voluntary and active participation of patients and are therefore prone to selection bias. To investigate the suitability of PROMs as real-world data, we investigated the real-world representativeness of the Prospective Observational Cohort Study of Esophageal-Gastric Cancer Patients (POCOP) registry with respect to the Dutch population of patients with esophagogastric cancer. Methods: We identified 2,575 patients in the POCOP registry and 13,702 in the nationwide population-based Netherlands Cancer Registry (NCR) from 2016-2021. We used Representativeness-indicators (R-indicators) to investigate the degree to which the POCOP registry and clinically relevant subgroups thereof, were a representative sample with respect to the population. R-indicators express the representativeness between 0 (not representative) and 1 (perfect representativeness). Calibration methods using inverse propensity weighting were used to correct potential differences between POCOP and the population estimates. Subsequently, median and 5-year overall survival were calculated and compared between patients in the POCOP registry and in the population, to investigate the representativeness in terms of survival. Results: Representativeness of the entire POCOP registry was 0.73 (95% CI: 0.71-0.74). The overall representativeness of palliative patients was higher than that of potentially curable patients (0.89 (0.87-0.90) and 0.70 (0.68-0.71), respectively). Representativeness of most clinical subgroups stratified to treatment was good; R-indicators ranged between 0.8 to 1.0. Median survival of the NCR, POCOP and calibrated POCOP was 19, 32, and 23 months, respectively. The 5-year overall survival of patients in the NCR, POCOP and calibrated POCOP was 26%, 36%, and 27%, respectively. Conclusions: The real-world representativeness of patients who participated in PROMs was good when we accounted for treatment. This shows that in the analysis of PROMs stratification to treatment groups can lead to generalizable results to the population. Using complete non-stratified PROMs, real-world representativeness was lower and calibration methods could be used to correct differences between patients in the PROMs and the population.
Neoadjuvant chemoradiation in elderly Irish patients with esophageal cancer: A review of the clinical outcomes and toxicity.
Authors: Mc Laughlin Ronan Andrew , Almeraikhi Majid , Alkaabi Humaid , Bligh Fianait , Cluxton Christopher , Mcmahon David , Fitzpatrick Orla , Conroy Michael R , Hennessy Bryan T. , O'Neill Brian , Naidoo Jarushka , Breathnach Oscar S. , Grogan William , Murphy Adrian Gerard , Morris Patrick G. 
Published: January 2023

335 Background: In locally advanced esophageal cancer, neoadjuvant chemo-radiotherapy improves survival compared with surgery alone. In the Chemo-Radiotherapy for Oesophageal cancer followed by Surgery Study (CROSS), the median age was 60. However, 1/3 of patients diagnosed with esophageal cancer are over 70 years. The CROSS outcomes are therefore limited in its application to older patients. The objective of this study is to report and compare the outcomes and tolerability in elderly patients (≥70 years), who underwent neoadjuvant chemo-radiation for esophageal cancer with younger patients < 70 years. Methods: A retrospective analysis of patients treated with neoadjuvant chemo-radiation for esophageal cancer between 1st January 2015 and 1st January 2021 was completed. Baseline characteristics and haematological toxicities were reported. Pathological response was reported. Survival was estimated using the Kaplan-Meier method. Results: In total 105 patients were included; 35 (33%) were ≥ 70 years and 70 (67%) patients were < 70 years. In the elderly cohort, the median age was 75 (70-86) and the younger cohort median age was 60 (29-69). 73% of patients in each cohort were male. 31 (89%) of older adults experienced any grade of anaemia compared with 45 (64%) of the younger cohort. Only one patient experienced ≥ grade 3 anaemia in each cohort. 18(51%) and 33(47%) of older and younger patients respectively experienced any grade of neutropenia. 5(14%) older and 7(10%) younger patients experienced ≥ grade 3 neutropenia. 15(43%) and 43(61%) of older and younger patients experienced any grade of thrombocytopenia. No patients experienced ≥ grade 3 thrombocytopenia. 80% of the older and 86% of the younger cohort proceeded to surgery. 3(11%) and 17(29%) of the older and younger cohorts respectively who underwent surgery achieved a complete pathological response. There was no difference in overall survival (OS) between the cohorts (p=0.48). There was also no difference in progression free survival (PFS) between the cohorts. Conclusions: In conclusion, we confirm that neoadjuvant chemo-radiation is tolerable in patients ≥ 70 when compared with patients < 70 years. Both OS and PFS is similar in both cohorts. We recommend the use of neoadjuvant therapy in appropriately selected patients ≥ 70 years.
Esophagogastrostomy with fundoplication versus double-tract reconstruction after laparoscopic proximal gastrectomy for gastric cancer.
Authors: Tominaga Shinta , Ojima Toshiyasu , Hayata Keiji , Kitadani Junya , Yamaue Hiroki , Kawai Manabu 
Published: January 2023

346 Background: Upper-third gastric cancer has been increasing in incidence worldwide and performance of laparoscopic proximal gastrectomy has become increasing common. Various reconstructive procedures after laparoscopic proximal gastrectomy have been reported, but the optimal reconstructive procedure is unclear. Methods: This single-center retrospective study included 53 consecutive patients with early gastric cancer in the upper third of the stomach who received laparoscopic proximal gastrectomy at our hospital between September 2013 and November 2019. Of these 53 patients, 39 underwent esophagogastrostomy with fundoplication. In the 14 patients requiring resection of the abdominal esophagus or where the size of the remnant stomach was 50% or less, we performed double-tract reconstruction. We compared the surgical and nutritional outcomes of patients who underwent esophagogastrostomy or double-tract reconstruction after laparoscopic proximal gastrectomy. Results: There was no significant difference between the two groups regarding blood loss, incidence of postoperative complications, occurrence of gastroesophageal reflux disease, food intake, reflux symptoms, or usage of proton pump inhibitors. There was no significant difference in the rate of body weight change at 6 or 12 months, or in biochemical markers (hemoglobin, total protein and albumin) at 12 months. However, eight patients (21%) in the esophagogastrostomy group had extreme body weight loss (≥20%) within 12 months. Conversely, in the double-tract reconstruction group, no patients had any extreme body weight loss ( P = 0.013). Conclusions: Double-tract reconstruction is useful after laparoscopic proximal gastrectomy, especially in terms of preventing extreme body weight loss.