Cancer Research and Treatment

Original Articles

Molecular Mosaics: Unveiling Heterogeneity in Synchronous Colorectal Cancers: Hyun Gu Lee, Yeseul Kim, Mi-Ju Kim, Yeon Wook Kim, Sun-Young Jun, Deokhoon Kim, In Ja Park, Seung-Mo Hong; Received September 30, 2024 Accepted February 17, 2025 Published online February 18, 2025; DOI: https://doi.org/10.4143/crt.2024.947 [Accepted]

Abstract PDF: Purpose
Molecular characteristics of synchronous colorectal cancers (SCRCs) remain incompletely elucidated, despite their importance in targeted therapy selection. We compared the molecular characteristics and somatic mutations between SCRCs.
Materials and Methods
This retrospective study (2012-2014) included 98 consecutive patients with surgically resected SCRCs. Molecular characteristics, including microsatellite instability (MSI) and tumor-infiltrating lymphocytes (TILs), were analyzed for all cancer lesions. The intertumoral heterogeneity of SCRCs was evaluated using whole-exome sequencing (WES) for 18 cancers from 9 patients with at least one MSI-high (MSI-H) tumor.
Results
Twelve patients had at least one MSI-H tumor; five showed discordant MSI status. Mucinous adenocarcinoma frequency and TIL density were higher in patients with at least one MSI-H tumor than in those with only microsatellite-stable tumors. WES revealed that, except one patient (6.5%), most synchronous cancers shared few variants in each patient (0.09–0.36%). The concordance rates for BRAF, KRAS, NRAS, and PIK3CA in synchronous cancers from each patient were 66.7%, 66.7%, 66.7%, and 55.6%, respectively.
Conclusion
Although synchronous cancers shared a mutated gene, the mutation subtypes differed. SCRCs exhibited 5.1% MSI status discordance rate and a high discordance rate in somatic mutational variants. As intertumoral heterogeneity may affect the targeted therapy response, molecular analysis of all tumors is recommended for patients with SCRCs.

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Gastrointestinal cancer

Radiofrequency Ablation versus Stereotactic Body Radiation Therapy in the Treatment of Colorectal Cancer Liver Metastases: Jesang Yu, Dong Hwan Kim, Jungbok Lee, Yong Moon Shin, Jong Hoon Kim, Sang Min Yoon, Jinhong Jung, Jin Cheon Kim, Chang Sik Yu, Seok-Byung Lim, In Ja Park, Tae Won Kim, Yong Sang Hong, Sun Young Kim, Jeong Eun Kim, Jin-hong Park, So Yeon Kim; Cancer Res Treat. 2022;54(3):850-859. Published online October 13, 2021; DOI: https://doi.org/10.4143/crt.2021.674

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Purpose
This study aimed to compare the treatment outcomes of radiofrequency ablation (RFA) and stereotactic body radiation therapy (SBRT) for colorectal cancer liver metastases (CRLM) and to determine the favorable treatment modality according to tumor characteristics.
Materials and Methods
We retrospectively analyzed the records of 222 colorectal cancer patients with 330 CRLM who underwent RFA (268 tumors in 178 patients) or SBRT (62 tumors in 44 patients) between 2007 and 2014. Kaplan–Meier method and Cox models were used by adjusting with inverse probability of treatment weighting (IPTW).
Results
The median follow-up duration was 30.5 months. The median tumor size was significantly smaller in the RFA group than in the SBRT group (1.5 cm vs 2.3 cm, p<0.001). In IPTW-adjusted analysis, difference in treatment modality was not associated with significant differences in 1-year and 3-year recurrence-free survival (35% vs 43%, 22% vs 23%; p=0.198), overall survival (96% vs 91%, 58% vs 56%; p=0.508), and freedom from local progression (FFLP; 90% vs 72%, 78% vs 60%; p=0.106). Significant interaction effect between the treatment modality and tumor size was observed for FFLP (p=0.001). In IPTW-adjusted subgroup analysis of patients with tumor size >2 cm, the SBRT group had a higher FFLP compared with the RFA group (HR, 0.153; p<0.001).
Conclusion
SBRT and RFA showed similar local control in the treatment of patients with CRLM. Tumor size was an independent prognostic factor for local control and SBRT may be preferred for larger tumors.

Citations

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Ablative techniques in colorectal liver metastases: A systematic review, descriptive summary of practice, and recommendations for optimal data reporting
Wee Han Ng, Catarina Machado, Alice Rooney, Robert Jones, Jonathan Rees, Samir Pathak
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Effects of maximum dose on local control after stereotactic body radiotherapy for oligometastatic tumors of colorectal cancer
Su Jin Kang, Jongmoo Park, Gyu-Seog Choi, Jong Gwang Kim, Jun Seok Park, Hye Jin Kim, Jin Ho Baek, Byung Woog Kang, An Na Seo, Shin-Hyung Park, Bong Kyung Bae, Min Kyu Kang, Soo Yeun Park, Devarati Mitra
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Role of Radiotherapy in Liver Tumors: Recent Update
Vito Filbert Jayalie, Merinda, Herryanto Lumbantobing, Sudibio, Julius Oentario, Hendriyo, Sry Suryani Widjaja
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Clayton T. Marcinak, Patrick B. Schwartz, Mustafa M. Basree, Newton Hurst, Michael Bassetti, Jeremy D. Kratz, Nataliya V. Uboha
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D. Pezzulla, G. Chiloiro, E. M. Lima, G. Macchia, C. Romano, S. Reina, G. Panza, S. Cilla, A. G. Morganti, F. Cellini, M. A. Gambacorta, F. Deodato
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Max Seidensticker
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Erratum

ERRATUM: Prognostic Implications of Extranodal Extension in Relation to Colorectal Cancer Location: Chan Wook Kim, Jihun Kim, Yangsoon Park, Dong-Hyung Cho, Jong Lyul Lee, Yong Sik Yoon, In Ja Park, Seok-Byung Lim, Chang Sik Yu, Jin Cheon Kim; Cancer Res Treat. 2021;53(3):893-893. Published online June 8, 2021; DOI: https://doi.org/10.4143/crt.2018.392.E; Corrects: Cancer Res Treat 2019;51(3):1135

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Original Articles

Association of Body Composition with Long-Term Survival in Non-metastatic Rectal Cancer Patients: Jin Soo Han, Hyoseon Ryu, In Ja Park, Kyung Won Kim, Yongbin Shin, Sun Ok Kim, Seok-Byung Lim, Chan Wook Kim, Yong Sik Yoon, Jong Lyul Lee, Chang Sik Yu, Jin Cheon Kim; Cancer Res Treat. 2020;52(2):563-572. Published online December 3, 2019; DOI: https://doi.org/10.4143/crt.2019.249

Abstract PDF PubReader ePub

Purpose
We evaluated the association of body composition with long-term oncologic outcomes in non-metastatic rectal cancer patients.
Methods
We included 1,384 patients with stage(y)0-III rectal cancer treated at Asan Medical Center between January 2005 and December 2012. Body composition at diagnosis was measured using abdomino-pelvic computed tomography (CT). Sarcopenia, visceral obesity (VO), and sarcopenic obesity (SO) were defined using CT measured parameters such as skeletal muscle index (total abdominal muscle area, TAMA), visceral fat area (VFA), and VFA/TAMA. Inflammatory status was defined as a neutrophil-lymphocyte ratio of ≥3. Obesity was categorized by body mass index (≥ 25 kg/m²).
Results
Among the 1,384 patients, 944 (68.2%) had sarcopenia and 307 (22.2%) had SO. The 5-year overall survival (OS) rate was significantly lower in sarcopenic patients (no sarcopenia vs. sarcopenia; 84% vs. 78%, p=0.003) but the 5-year recurrence-free survival (RFS) rate was not different (77.3% vs. 77.9% p=0.957). Patients with SO showed lower 5-year OS (79.1% vs. 75.5% p=0.02) but no difference in 5-year RFS (p=0.957). Sarcopenia, SO, VO, and obesity were not associated with RFS. However, obesity, SO, age, sex, inflammatory status, and tumor stage were confirmed as independent factors associated with OS on multivariate analysis. In subgroup analysis, association of SO with OS was more prominent in patients with (y)p stage 0-2 and no inflammatory status.
Conclusion
The presence of SO and a low body mass index at diagnosis are negatively associated with OS in non-metastatic rectal cancer patients.

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Prognostic Implications of Extranodal Extension in Relation to Colorectal Cancer Location: Chan Wook Kim, Jihun Kim, Yangsoon Park, Dong-Hyung Cho, Jong Lyul Lee, Yong Sik Yoon, In Ja Park, Seok-Byung Lim, Chang Sik Yu, Jin Cheon Kim; Cancer Res Treat. 2019;51(3):1135-1143. Published online November 29, 2018; DOI: https://doi.org/10.4143/crt.2018.392; Correction in: Cancer Res Treat 2021;53(3):893

Abstract PDF PubReader ePub

Purpose
Extranodal extension (ENE) is closely associated with the aggressiveness of both colon and rectal cancer. This study evaluated the clinicopathologic significance and prognostic impact of ENE in separate populations of patients with colon and rectal cancers.
Materials and Methods
The medical records of 2,346 patients with colorectal cancer (CRC) who underwent curative surgery at our institution between January 2003 and December 2011 were clinically and histologically reviewed.
Results
ENE was associated with younger age, advanced tumor stage, lymphovascular invasion (LVI), and perineural invasion (PNI) in both colon and rectal cancer. ENE rates differed significantly in patients with right colon (36.9%), left colon (42.6%), and rectal (48.7%) cancers (right vs. left, p=0.037; left vs. rectum, p=0.009). The 5-year disease-free survival (DFS) rate according to ENE status and primary tumor site differed significantly in patients with ENE-negative colon cancer (80.5%), ENE-negative rectal cancer (77.4%), ENE-positive colon cancer (68.6%), and ENE-positive rectal cancer (64.2%) (p<0.001). Multivariate analysis showed that advanced tumor stage, ENE, LVI, PNI, and absence of adjuvant chemotherapy were independently prognostic of reduced DFS in colon and rectal cancer patients.
Conclusion
ENE is closely associated with the aggressiveness of colon and rectal cancers, with its frequency increasing from the right colon to the left colon to the rectum. ENE status is a significant independent predictor of DFS in CRC patients irrespective of tumor location. ENE might be more related with distally located CRC.

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Case Report

Lymph Node Metastases of Prostatic Adenocarcinoma in the Mesorectum in Patients with Rectal Cancer: In Ja Park, Hee Cheol Kim, Chang Sik Yu, Choung Soo Kim, Jung Sun Kim, Jin Cheon Kim; Cancer Res Treat. 2005;37(2):129-132. Published online April 30, 2005; DOI: https://doi.org/10.4143/crt.2005.37.2.129

Abstract PDF PubReader ePub

Lymph node involvement is the most important prognostic factor of rectal cancer. Cancer originating from sites other than the rectum rarely metastasizes to the mesorectal lymph node. We report a rectal cancer patient with a synchronous metastatic prostatic carcinoma to the mesorectal lymph node.

Citations

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A Case of Rectal Cancer with Lymph Node Metastasis of Prostate Cancer in the Mesorectum after Radical Prostatectomy
Teruhisa UDAGAWA, Yu SUZUKI, Yasushi ITO, Yoshihisa TAMATE, Naoki YANAGAWA, Takashi KAMEI
Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association).2022; 83(4): 775. CrossRef
Two Cases of Colorectal Cancer with Mesenteric Lymph Node Metastasis Derived from Prostatic Cancer
Fumitaka Asahara, Hirotoshi Hasegawa, Shutaro Suda, Emima Bekku, Kazuhiko Hashimoto, Aya Sasaki, Junichi Matsui
The Japanese Journal of Gastroenterological Surgery.2020; 53(1): 61. CrossRef
Metastasization of mesorectal lymph nodes by a prostatic adenocarcinoma
J.J. Arenal, A. Torres, C. Tinoco, M.A. Citores, C. Benito, B. Madrigal, A. Vara
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Original Articles

Responsiveness of CPT-11 in Respect to hMLH1 and hMSH2 Protein Expression in the Primary Colorectal Cancer: In Ja Park, Hee Cheol Kim, Chang Sik Yu, Heung Moon Chang, Jea Hwan Lee, Jong Hoon Kim, Tae Won Kim, Jung Sun Kim, Jin Cheon Kim; Cancer Res Treat. 2004;36(6):360-366. Published online December 31, 2004; DOI: https://doi.org/10.4143/crt.2004.36.6.360

Abstract PDF PubReader ePub: Purpose
The aim of this study was to evaluate the responsiveness to CPT-11 with respect to hMLH1 and hMSH2 protein expressions in primary colorectal tumors.
Materials and Methods
91 patients with colorectal cancer treated having undergone surgery and postoperative CPT-11-based adjuvant chemotherapy, between 1997 and 2002, were prospectively recruited. Tumor samples were immunohistochemically analyzed for the expressions of hMLH1, hMSH2, p53 and CEA proteins.
Results
Of the 91 tumors, 6 (6.6%) and 4 (4.4%) showed loss of hMLH1 and hMSH2 protein expressions, respectively. The response rate of patients with tumors not expressing either hMLH1 or hMSH2 was higher than that of those expressing either of these proteins (p=0.026). Patients with tumors not expressing hMLH1 showed a significantly better response to CPT-11 (p=0.04). The responsiveness was not associated with the expressions of hMSH2, p53 or CEA. There were no correlations between drug toxicity and the expressions of hMLH1, hMSH2 or p53. The overall survival was better in patients responsive to CPT-11-based chemotherapy compared to non-responders.
Conclusion
The immunohistochemical determination of loss of hMLH1 and hMSH2 expressions may be used in determining the responsiveness to CPT-11-based chemotherapy. Our results suggest that hMLH1 protein expression may be a predictor for CPT-11 responsiveness in patients with colorectal cancer.

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Immunohistochemical Expression of bcl-2 and p53 in Breast Carcinomas: Young Euy Park, Jin Ja Park, Kyung Chan Choi, Hyung Shik Shin, Young Euy Park; J Korean Cancer Assoc. 1996;28(5):787-796.

Abstract PDF: The immunohistochemical expression of bcl-2 and p53 protein was evaluated in formali-fixed, paraffin embedded surgical specimens from 107 patients with breast carcinoma. bcl-2 protein was found to be expressed in 66 specimens(62.9%). Bcl-2 expression was correlated with good prognostic factors such as well differentiation, low grade nuclear atypism, few mitoses or absence of lymph node metastasis. p53 protein expression was detected in 60 cases(56.6%). An inverse correlation was observed between of bcl-2 and p53(R=0.l9863, p< 0.05). These findings suggest that overexpression(mutation) of p53 and/or bcl-2 protein may be early events in tumorigenesis and that p53 alterations in particular are essential for maintenance of a malignant phenotype in tumour development.

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