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Gastrointestinal Cancer
LASSO-Based Machine Learning Algorithm for Prediction of Lymph Node Metastasis in T1 Colorectal Cancer
Jeonghyun Kang, Yoon Jung Choi, Im-kyung Kim, Hye Sun Lee, Hogeun Kim, Seung Hyuk Baik, Nam Kyu Kim, Kang Young Lee
Cancer Res Treat. 2021;53(3):773-783.   Published online December 29, 2020
DOI: https://doi.org/10.4143/crt.2020.974
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The role of tumor-infiltrating lymphocytes (TILs) in predicting lymph node metastasis (LNM) in patients with T1 colorectal cancer (CRC) remains unclear. Furthermore, clinical utility of a machine learning–based approach has not been widely studied.
Materials and Methods
Immunohistochemistry for TILs against CD3, CD8, and forkhead box P3 in both center and invasive margin of the tumor were performed using surgically resected T1 CRC slides. Three hundred and sixteen patients were enrolled and categorized into training (n=221) and validation (n=95) sets via random sampling. Using clinicopathologic variables including TILs, the least absolute shrinkage and selection operator (LASSO) regression model was applied for variable selection and predictive signature building in the training set. The predictive accuracy of our model and the Japanese criteria were compared using area under the receiver operating characteristic (AUROC), net reclassification improvement (NRI)/integrated discrimination improvement (IDI), and decision curve analysis (DCA) in the validation set.
Results
LNM was detected in 29 (13.1%) and 12 (12.6%) patients in training and validation sets, respectively. Nine variables were selected and used to generate the LASSO model. Its performance was similar in training and validation sets (AUROC, 0.795 vs. 0.765; p=0.747). In the validation set, the LASSO model showed better outcomes in predicting LNM than Japanese criteria, as measured by AUROC (0.765 vs. 0.518, p=0.003) and NRI (0.447, p=0.039)/IDI (0.121, p=0.034). DCA showed positive net benefits in using our model.
Conclusion
Our LASSO model incorporating histopathologic parameters and TILs showed superior performance compared to conventional Japanese criteria in predicting LNM in patients with T1 CRC.

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Which Patients with Isolated Para-aortic Lymph Node Metastasis Will Truly Benefit from Extended Lymph Node Dissection for Colon Cancer?
Sung Uk Bae, Hyuk Hur, Byung Soh Min, Seung Hyuk Baik, Kang Young Lee, Nam Kyu Kim
Cancer Res Treat. 2018;50(3):712-719.   Published online July 14, 2017
DOI: https://doi.org/10.4143/crt.2017.100
AbstractAbstract PDFPubReaderePub
Purpose
The prognosis of patientswith colon cancer and para-aortic lymph node metastasis (PALNM) is poor. We analyzed the prognostic factors of extramesenteric lymphadenectomy for colon cancer patients with isolated PALNM.
Materials and Methods
We retrospectively reviewed 49 patients with PALNM who underwent curative resection between October 1988 and December 2009.
Results
In univariate analyses, the 5-year overall survival (OS) and disease-free survival (DFS) rates were higher in patients with ≤ 7 positive para-aortic lymph node (PALN) (36.5% and 27.5%) than in those with > 7 PALN (14.3% and 14.3%; p=0.010 and p=0.027, respectively), and preoperative carcinoembryonic antigen (CEA) level > 5 was also correlated with a lower 5-year OS and DFS rate of 21.5% and 11.7% compared with those with CEA ≤ 5 (46.3% and 41.4%; p=0.122 and 0.039, respectively). Multivariate analysis found that the number of positive PALN (hazard ratio [HR], 3.291; 95% confidence interval [CI], 1.309 to 8.275; p=0.011) was an independent prognostic factor for OS and the number of positive PALN (HR, 2.484; 95% CI, 0.993 to 6.211; p=0.052) and preoperative CEA level (HR, 1.953; 95% CI, 0.940 to 4.057; p=0.073) were marginally independent prognostic factors for DFS. According to our prognostic model, the 5-year OS and DFS rate increased to 59.3% and 53.3%, respectively, in patients with ≤ 7 positive PALN and CEA level ≤ 5.
Conclusion
PALN dissection might be beneficial in carefully selected patients with a low CEA level and less extensive PALNM.

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p16 Hypermethylation and KRAS Mutation Are Independent Predictors of Cetuximab Plus FOLFIRI Chemotherapy in Patients with Metastatic Colorectal Cancer
Se Hyun Kim, Kyu Hyun Park, Sang Joon Shin, Kang Young Lee, Tae Il Kim, Nam Kyu Kim, Sun Young Rha, Jae Kyung Roh, Joong Bae Ahn
Cancer Res Treat. 2016;48(1):208-215.   Published online April 24, 2015
DOI: https://doi.org/10.4143/crt.2014.314
AbstractAbstract PDFPubReaderePub
Purpose
Hypermethylation of the CpG island of p16INK4a occurs in a significant proportion of colorectal cancer (CRC). We aimed to investigate its predictive role in CRC patients treated with 5-fluorouracil, leucovorin, irinotecan (FOLFIRI), and cetuximab.
Materials and Methods
Pyrosequencing was used to identify KRASmutation and hypermethylation of 6 CpG island loci (p16, p14, MINT1, MINT2, MINT31, and hMLH1) in DNA extracted from formalin-fixed paraffin-embedded specimens. Logistic regression and Cox regression were performed for analysis of the relation between methylation status of CpG island methylator phenotype (CIMP) markers including p16 and clinical outcome.
Results
Hypermethylation of the p16 gene was detected in 14 of 49 patients (28.6%) and showed significant association with KRASmutation (Fisher exact, p=0.01) and CIMP positivity (Fisher exact, p=0.002). Patients with p16-unmethylated tumors had significantly longer time to progression (TTP; median, 9.0 months vs. 3.5 months; log-rank, p=0.001) and overall survival (median, 44.9 months vs. 16.4 months; log-rank, p=0.008) than those with p16-methylated tumors. Patients with both KRAS and p16 aberrancy (n=6) had markedly shortened TTP (median, 2.8 months) compared to those with either KRAS or p16 aberrancy (n=11; median, 8.6 months; p=0.021) or those with neither (n=32; median, 9.0 months; p < 0.0001). In multivariate analysis, KRAS mutation and p16 methylation showed independent association with shorter TTP (KRAS mutation: hazard ratio [HR], 3.21; p=0.017; p16 methylation: HR, 2.97; p=0.027).
Conclusion
Hypermethylation of p16 was predictive of clinical outcome in metastatic CRC patients treated with cetuximab and FOLFIRI, irrespective of KRAS mutation.

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  • Prediction of Response to Anti-Angiogenic Treatment for Advanced Colorectal Cancer Patients: From Biological Factors to Functional Imaging
    Giuseppe Corrias, Eleonora Lai, Pina Ziranu, Stefano Mariani, Clelia Donisi, Nicole Liscia, Giorgio Saba, Andrea Pretta, Mara Persano, Daniela Fanni, Dario Spanu, Francesca Balconi, Francesco Loi, Simona Deidda, Angelo Restivo, Valeria Pusceddu, Marco Puz
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Novel Methods for Clinical Risk Stratification in Patients with Colorectal Liver Metastases
Ki-Yeol Kim, Nam Kyu Kim, In-Ho Cha, Joong Bae Ahn, Jin Sub Choi, Gi-Hong Choi, Joon Suk Lim, Kang Young Lee, Seung Hyuk Baik, Byung Soh Min, Hyuk Hur, Jae Kyung Roh, Sang Joon Shin
Cancer Res Treat. 2015;47(2):242-250.   Published online September 11, 2014
DOI: https://doi.org/10.4143/crt.2014.066
AbstractAbstract PDFPubReaderePub
Purpose
Colorectal cancer patients with liver-confined metastases are classified as stage IV, but their prognoses can differ from metastases at other sites. In this study, we suggest a novel method for risk stratification using clinically effective factors. Materials and Methods Data on 566 consecutive patients with colorectal liver metastasis (CLM) between 1989 and 2010 were analyzed. This analysis was based on principal component analysis (PCA). Results The survival rate was affected by carcinoembryonic antigen (CEA) level (p < 0.001; risk ratio, 1.90), distribution of liver metastasis (p=0.014; risk ratio, 1.46), and disease-free interval (DFI; p < 0.001; risk ratio, 1.98). When patients were divided into three groups according to PCA score using significantly affected factors, they showed significantly different survival patterns (p < 0.001). Conclusion The PCA scoring system based on CEA level, distribution of liver metastasis, and DFI may be useful for preoperatively determining prognoses in order to assist in clinical decisionmaking and designing future clinical trials for CLM treatment.

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    Juan Garona, Natasha T. Sobol, Marina Pifano, Valeria I. Segatori, Daniel E. Gomez, Giselle V. Ripoll, Daniel F. Alonso
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Efficacy of Postoperative Concurrent Chemoradiation for Resectable Rectal Cancer: A Single Institute Experience
Joong Bae Ahn, Hee Chul Chung, Nae Choon Yoo, Jae Kyung Roh, Nam Kyu Kim, Chang Ok Suh, Gwi Eon Kim, Jin Sil Seong, Woong Ho Shim, Hyun Cheol Chung
Cancer Res Treat. 2004;36(4):228-234.   Published online August 31, 2004
DOI: https://doi.org/10.4143/crt.2004.36.4.228
AbstractAbstract PDFPubReaderePub
Purpose

For patients with Dukes' stage B and C rectal cancer, surgery followed by adjuvant chemoradiotherapy is considered to be the standard treatment. However, the drugs used in combination with 5-fluorouracil (5-FU), the method of administration, duration of adjuvant therapy and the frequencies of administration presently remain controversial topics. We investigated (1) the efficacy and safety of adjuvant radiotherapy and 5-FU/leucovorin (LV) chemotherapy for patients who had undergone curative resection and (2) the effect of dose related factors of 5-FU on survival.

Materials and Methods

130 rectal cancer patients with Dukes' B or C stage disease who were treated with curative resection were evaluated. The adjuvant therapy consisted of two cycles of 5-FU/LV chemotherapy followed by pelvic radiotherapy with chemotherapy, and then 4~10 more cycles of the same chemotherapy regimen were delivered based on the disease stage. The cumulative dose of 5-FU per body square meter (BSA), actual dose intensity and relative dose intensity were obtained. The patients were divided into two groups according to the median value of each factor, and the patients' survival rates were compared.

Results

With a median follow-up duration of 52 months, the 5-year disease-free survival and overall survival rates of 130 patients were 57% and 73%, respectively. Locoregional failure occurred in 17 (13%) of the 130 patients, and the distant failure rate was 27% (35/130). The chemotherapy related morbidity was minimal, and there was no mortality for these patients. The cumulative dose of 5-FU/BSA had a significant effect on the 5-year overall survival for Dukes' C rectal cancer patients (p=0.03). Multivariate analysis demonstrated that only the performance status affected the 5-year overall survival (p=0.003).

Conclusion

An adjuvant therapy of radiotherapy and 5-FU/LV chemotherapy is effective and tolerable for Dukes' B and C rectal cancer patients. A prospective, multicenter, randomized study to evaluate the effects of the cumulative dose of 5-FU/BSA on survival is required.

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  • Seven low-mass ions in pretreatment serum as potential predictive markers of the chemoradiotherapy response of rectal cancer
    Kangsan Roh, Seung-Gu Yeo, Byong Chul Yoo, Kyung-Hee Kim, Sun Young Kim, Min-Jeong Kim
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    Nurul Ainin Abdul Aziz, Norfilza M. Mokhtar, Roslan Harun, Md Manir Hossain Mollah, Isa Mohamed Rose, Ismail Sagap, Azmi Mohd Tamil, Wan Zurinah Wan Ngah, Rahman Jamal
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    Seung Ho Shin, Sun-Il Lee, Dong-Jin Choi, Si-Uk Woo, Jin Kim, Byung-Wook Min, Hong-Young Moon, Seon Hahn Kim
    Journal of the Korean Society of Coloproctology.2009; 25(6): 429.     CrossRef
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Cell Kinetics Studies of Human Epithelial Cancers with Bromodeoxyuridine Labeling
Jin Sil Seong, Jung Woon Lee, Eun Ji Chung, Yung Tae Kim, Jae Wook Kim, Nam Kyu Kim, Sung Joon Hong, Eun Chan Choi, Won Sang Lee, Oh Hun Kwon, Gwi Eon Kim
J Korean Cancer Assoc. 1995;27(5):783-790.
AbstractAbstract PDF
Cell kinetic parameters of labeling index (LI), duration of S-phase (Ts), and potential doubling time (Tpot) were analyzed following infusion of bromodeoxyuridine (BUdR) in 33 patients with various epithelial cancers. Twelve uterine cervical cancers, 9 rectal cancers, 7 head and neck caneers, and 5 bladder cancers were included. Biopsies were taken about 4-6 h after 200 mg/m(2) BUdR infusion and the samples were anaiyzed with bivariate DNA /BUdR flow cytometry. The distribution of cell kinetic parameters for the 33 epithelial cancers showed a large range of values for each parameter. The median LI, Ts, and Tpot were 4.5%, 10.8 h, and 242.3 h, respectively. Eight among 33 patients (24.2%) showed aneuploidy. In aneuploid tumors the distribution of LI, Ts, and Tpot was in relatively small range. Aneupliod tumors appeared to show higher LI and shorter Tpot than those in diploid tumors. In diploid tumors, the poesibility of normal cell contamination could not be ruled out. The results of this study would be a basis for future trial to predict which ones would show tumor clonogen repopulation during radiotherapy so that benefit from altered fractionated radiotherapy.
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