Cancer Research and Treatment

Original Articles

Real-World Efficacy of First-Line Nivolumab Plus Ipilimumab and Its Practical Predictive Biomarkers in Advanced Renal Cell Carcinoma: First Analysis from RENOIR Study (KCSG GU22-13): Jwa Hoon Kim, Sang Joon Shin, Woo Kyun Bae, Se Hyun Kim, Jin Young Kim, Hyeon-Su Im, In-Ho Kim, Il Hwan Kim, Kwonoh Park, Eo Jin Kim, Mihong Choi, Joo Han Lim, Hyunho Kim, Kyoungmin Lee, Hyo-Jeong Kim, Jungmin Jo, Hyo Jin Lee, Dalyong Kim, Byeong Seok Sohn, Inkeun Park, Ji Hyun Park; Received August 8, 2025 Accepted October 11, 2025 Published online October 13, 2025; DOI: https://doi.org/10.4143/crt.2025.846 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
We investigated the real-world efficacy of first-line nivolumab plus ipilimumab (NI) and its predictive clinicopathological biomarkers in patients with advanced renal cell carcinoma (aRCC).
Materials and Methods
We retrospectively analyzed 466 patients with aRCC who started first-line NI between 2019 and 2023 at 21 Korean tertiary hospitals. The primary outcome was objective response rate (ORR). Secondary outcomes were duration of response (DoR), progression-free survival (PFS), overall survival (OS), and identification of practical clinicopathological biomarkers.
Results
Median age of patients was 65 years, and 77.7% were male. ORR was 44.8% including 5.2% of complete response, and median DoR was 39.8 months. Male sex and lung metastasis were predictive markers of objective response, and achieving complete response was significantly associated with a longer DoR (p=0.03). With a median follow-up duration of 23.7 months, the median PFS and OS were 11.5 and 44.2 months, respectively. Full exposure to 4 cycles of ipilimumab was significantly associated with better PFS and OS. Durable response could significantly predict better OS, whereas multiple metastatic sites (≥ 4) and poor IMDC risk were two independent predictors for inferior OS. Among the 50 patients who completed 2 years of NI treatment, continuation of nivolumab beyond 2 years has marginally improved OS (p=0.09).
Conclusion
First-line NI showed comparable and competent efficacy in Korean patients with aRCC. We suggest completing full exposure to ipilimumab and durable response as practical predictors of enriched benefits of NI in our real-world.

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Gastrointestinal cancer

Non-operative Management of Rectal Cancer with Adjuvant Chemotherapy after Chemoradiotherapy (NORMANDY): Prospective Study: Hyebin Lee, Hyung Ook Kim, Jason Joon Bock Lee, In-Gu Do, Heon-Ju Kwon, Mi Sung Kim, Soo-Kyung Park, Hyo-Joon Yang, Yoon Suk Jung, Jung Ho Park, Dong-Il Park, Kyung Uk Jung, Eo Jin Kim, Dong-Hoe Koo, Hungdai Kim, Ho-Kyung Chun, KBSMC Colorectal Cancer Team, Gastrointestinal Cancer Center; Cancer Res Treat. 2026;58(2):573-580. Published online May 15, 2025; DOI: https://doi.org/10.4143/crt.2025.148

Abstract PDF Supplementary Material PubReader ePub: Purpose
Non-operative management (NOM) has emerged as a promising organ-preserving strategy for patients with rectal cancer who achieve a clinical complete response (cCR) after neoadjuvant chemoradiotherapy (CRT). However, no standardized treatment protocol has been established for watch-and-wait strategies.
Materials and Methods
This prospective study evaluated oncological outcomes of NOM combined with 4 months of adjuvant capecitabine. Patients with resectable rectal cancer (≤ 8 cm from the anal verge, cT2-4 or N+) underwent CRT (50-54 Gy in 25-27 fractions with capecitabine). Eight weeks post-CRT, a multidisciplinary team assessed cCR. Patients achieving cCR received six cycles of capecitabine (2 weeks on/1 week off) and were actively monitored.
Results
Among 89 patients receiving CRT (2018-2023), 17 (19.1%) achieved cCR and were included. The median age was 65 years, and 64.7% were male. Eleven (64.7%) completed all six cycles of adjuvant therapy. After a median follow-up of 31.4 months, 11 patients (64.7%) remained disease-free. Local regrowth occurred in six patients (35.3%) with 2- and 4-year rates of 34.5% and 47.6%, respectively. Five underwent radical surgery, and one received transanal excision with systemic chemotherapy. At the time of assessment, 15 patients (88.2%) showed no evidence of disease, while two (11.8%) received palliative chemotherapy. All patients were alive.
Conclusion
NOM with adjuvant capecitabine showed promising oncological outcomes, offering an alternative to passive watch-and-wait approaches. Further refinement through multidisciplinary strategies is warranted.

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Lung and Thoracic cancer

A Phase I/IIa Randomized Trial Evaluating the Safety and Efficacy of SNK01 Plus Pembrolizumab in Patients with Stage IV Non-Small Cell Lung Cancer: Eo Jin Kim, Yong-Hee Cho, Dong Ha Kim, Dae-Hyun Ko, Eun-Ju Do, Sang-Yeob Kim, Yong Man Kim, Jae Seob Jung, Yoonmi Kang, Wonjun Ji, Myeong Geun Choi, Jae Cheol Lee, Jin Kyung Rho, Chang-Min Choi; Cancer Res Treat. 2022;54(4):1005-1016. Published online December 3, 2021; DOI: https://doi.org/10.4143/crt.2021.986

Abstract PDF Supplementary Material PubReader ePub

Purpose
The aim of this study is to evaluate the safety and efficacy of ex vivo activated and expanded natural killer (NK) cell therapy (SNK01) plus pembrolizumab in a randomized phase I/IIa clinical trial.
Materials and Methods
Overall, 18 patients with advanced non–small cell lung cancer (NSCLC) and a programmed death ligand 1 tumor proportion score of 1% or greater who had a history of failed frontline platinum-based therapy were randomized (2:1) to receive pembrolizumab every 3 weeks +/– 6 weekly infusions of SNK01 at either 2×10⁹ or 4×10⁹ cells per infusion (pembrolizumab monotherapy vs. SNK01 combination). The primary endpoint was safety, whereas the secondary endpoints were the objective response rate (ORR), progression-free survival (PFS), overall survival, and quality of life.
Results
Since no dose-limiting toxicity was observed, the maximum tolerated dose was determined as SNK01 4×10⁹ cells/dose. The safety data did not show any new safety signals when SNK01 was combined with pembrolizumab. The ORR and the 1-year survival rate in the NK combination group were higher than those in patients who underwent pembrolizumab monotherapy (ORR, 41.7% vs. 0%; 1-year survival rate, 66.7% vs. 50.0%). Furthermore, the median PFS was higher in the SNK01 combination group (6.2 months vs. 1.6 months, p=0.001).
Conclusion
Based on the findings of this study, the NK cell combination therapy may consider as a safe treatment method for stage IV NSCLC patients who had a history of failed platinum-based therapy without an increase in adverse events.

Citations

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Adopting tomorrow’s therapies today: a perspective review of adoptive cell therapy in lung cancer
Faith Abodunrin, Daniel J Olson, Oluwatosin Emehinola, Christine M Bestvina
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Preclinical investigation of anti-tumor efficacy of allogeneic natural killer cells combined with cetuximab for head and neck squamous cell carcinoma
Chaeyeon Kim, Mina Han, Gamin Kim, Wonrak Son, Jeongah Kim, Minchan Gil, Yong-Hee Rhee, Nam Suk Sim, Chang Gon Kim, Hye Ryun Kim
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Tesfahun Dessale Admasu, John S. Yu
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Cytokines in Focus: IL-2 and IL-15 in NK Adoptive Cell Cancer Immunotherapy
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Chuan-Hsin Chang, Chih-Cheng Chien, Yue-Cune Chang
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Synergistic Anti-Tumor Efficacy of Modified FOLFIRINOX and NK Cell Therapy in Pancreatic Ductal Adenocarcinoma
Hye-Seong Park, Jun Eul Hwang, Je-Jung Lee, Woo Kyun Bae
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Machine learning-based development of a cytotoxicity prediction model for NK cell therapy in cancers
Jie Ma, Jingjing Yue, Yangyang Li, Yutong Li, Hongbo Dong, Fang Fang, Weihua Xiao
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Gastrointestinal cancer

Trends in Chemotherapy Patterns and Survival of Patients with Advanced Gastric Cancer over a 16-Year Period: Impact of Anti-HER2–Targeted Agent in the Real-World Setting: Dong-Hoe Koo, Min-Hee Ryu, Mi-Yeon Lee, Heejung Chae, Eo Jin Kim, Mee-Sun Moon, Yoon-Koo Kang; Cancer Res Treat. 2021;53(2):436-444. Published online October 6, 2020; DOI: https://doi.org/10.4143/crt.2020.725

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to evaluate the survivals of patients with metastatic or recurrent gastric cancer (MRGC) over a period of 16 years and to investigate the recent changes in chemotherapy patterns.
Materials and Methods
A total of 5,384 patients who received chemotherapy for MRGC between 2000 and 2015 were analyzed. The analysis focused on a comparison of the first-line chemotherapy between four periods: 2000–2003 (period 1), 2004–2007 (period 2), 2008–2011 (period 3), and 2012–2015 (period 4).
Results
There were 880 patients (16%) in period 1, 1,573 (29%) in period 2, 1,435 (27%) in period 3, and 1,496 (28%) in period 4. Cytotoxic doublet-based therapy was the most commonly used (78%) first-line chemotherapy, and the combination of trastuzumab and doublet chemotherapy was provided to 288 patients. The OS rates at 12 and 24 months were steadily improved as follows: 39.2% and 14.6% in period 1, 43.5% and 17.6% in period 2, 50.3% and 20.6% in period 3, and 51.7% and 24.1% in period 4, respectively (p < 0.001). Among the patients who received the doublet-based chemotherapy, the median OS of those who received trastuzumab was 18.0 months (95% CI, 15.5–20.6), while that of those who received other doublet therapies was 11.2 months (95% CI, 10.8–11.6).
Conclusion
The OS was improved over time with advancements in chemotherapy, particularly the introduction of the anti-HER2–targeted agent, which contributed to the increase in the number of long-term survivors and established the superiority of OS for the treatment of MRGC.

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Expression of Cyclooxygenase-2 and Tumor Microvessel Density in Colorectal Cancer: Seoung Wan Chae, Jin Hee Sohn, Eo Jin Kim, Eun Yoon Cho, Bong Hwa Lee; Cancer Res Treat. 2003;35(5):400-406. Published online October 31, 2003; DOI: https://doi.org/10.4143/crt.2003.35.5.400

Abstract PDF

PURPOSE
The increased expression of cyclooxygenase (COX)-2 has been implicated in the development and progression of human cancer. This study investigated the COX-2 expression in colorectal cancer, and its relationships with tumor angiogenesis and the clinicopathological factors. MATERIALS AND METHODS: The expression of the COX-2 protein and microvessel density were evaluated, using immunohistochemical methods, in 21 normal colonic mucosa and 190 human colorectal carcinomas. Correlations between COX-2 expression and microvessel density, as well as various clinicopathological factors, were studied in colorectal carcinomas. RESULTS: The COX-2 protein expression in epithelial cells was increased in 169 of the 190 adenocarcinoma cases (88.9%), but in only 1 of the 21 (4.8%) normal mucosa cases. The COX-2 expression was significantly increased in the differentiated compared with the undifferentiated colorectal carcinomas (p<0.05), and significantly correlated with the depth of invasion and microvessel density (p<0.05). Rectal cancers had more COX-2 positive cases than the colon cancers (p<0.05). However, there were no significant differences in the tumor size and the presence of lymphatic or vascular invasion. CONCLUSION: The overexpression of cyclooxygenase-2 in colorectal carcinomas seems to play a role in the invasion and angiogenesis of the tumors, so may be a useful marker of the prognosis. The prominent expression was also demonstrated in differentiated colorectal cancers.

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Expression of Cyclooxygenase (COX)-2 as a Prognostic Factor in Nasopharyngeal Cancer
Kyubo Kim, Hong-Gyun Wu, Suk Won Park, Chong Jai Kim, Charn Il Park
Cancer Research and Treatment.2004; 36(3): 187. CrossRef

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