Cancer Research and Treatment

Low-Dose Cyclophosphamide Enhances the Tumoricidal Effects of 5-Day Spacing Stereotactic Ablative Radiotherapy by Boosting Antitumor Immunity: Hyunkyung Kim, Seok-Joo Chun, Sojung Sun, Haeun Cho, Tae-Jin Kim, Yoon-Jin Lee, Eui Kyu Chie, Kwangmo Yang, Mi-Sook Kim; Received August 21, 2024 Accepted November 7, 2024 Published online November 8, 2024; DOI: https://doi.org/10.4143/crt.2024.807 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aimed to investigate the potential role of low-dose cyclophosphamide (Cy) as a radiosensitizer by evaluating its impact on the immune response and the abscopal effect of stereotactic ablative radiotherapy through preclinical models.
Materials and Methods
CT26 tumors (immunologically hot) and 4T1 tumors (immunologically cold), grown in immunocompetent BALB/c and immunodeficient BALB/c–nude mice, were irradiated with 20 Gy in two fractions with 5-day spacing followed by intraperitoneal injections of 9 mg/kg Cy every 3 days. Immunological changes in CT26 tumors caused by the treatments were assessed using flow cytometry. Changes in the expression of hypoxia-inducible factor-1α (HIF-1α) in tumors were also assessed. Splenocytes and bone marrow–derived dendritic cells (DCs) were exposed to various concentrations of Cy to assess T cell proliferation and DC differentiation.
Results
The combination of Cy with radiotherapy (RT+Cy) significantly suppressed tumor growth compared to RT alone in immunocompetent mice, while that effect was not observed in immunodeficient mice. Additionally, RT+Cy effectively induced abscopal effects in hot and cold tumors, with increased CD8+ T cells in blood and tumors. Significantly higher expression levels of granzyme B, interferon γ, and tumor necrosis factor α were observed in RT+Cy group compared to the RT alone group. In vitro data indicated that low-dose Cy promotes DC differentiation. Low-dose Cy suppressed the radiation-induced upregulation of HIF-1α in the tumors.
Conclusion
Low-dose Cy enhances tumoricidal effects of 5-day spacing high-dose RT by increasing antitumor immune responses.

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Gastrointestinal cancer

Prognostic Evaluation and Survival Prediction for Combined Hepatocellular-Cholangiocarcinoma Following Hepatectomy: Seok-Joo Chun, Yu Jung Jung, YoungRok Choi, Nam-Joon Yi, Kwang-Woong Lee, Kyung-Suk Suh, Kyoung Bun Lee, Hyun-Cheol Kang, Eui Kyu Chie, Kyung Su Kim; Cancer Res Treat. 2025;57(1):229-239. Published online July 3, 2024; DOI: https://doi.org/10.4143/crt.2024.176

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to assess prognostic factors associated with combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and to predict 5-year survival based on these factors.
Materials and Methods
Patients who underwent definitive hepatectomy from 2006 to 2022 at a single institution was retrospectively analyzed. Inclusion criteria involved a pathologically confirmed diagnosis of cHCC-CCA.
Results
A total of 80 patients with diagnosed cHCC-CCA were included in the analysis. The median progression-free survival was 15.6 months, while distant metastasis-free survival (DMFS), hepatic progression-free survival, and overall survival (OS) were 50.8, 21.5, and 85.1 months, respectively. In 52 cases of recurrence, intrahepatic recurrence was the most common initial recurrence (34/52), with distant metastasis in 17 cases. Factors associated with poor DMFS included tumor necrosis, lymphovascular invasion (LVI), perineural invasion, and histologic compact type. Postoperative carbohydrate antigen 19-9, tumor necrosis, LVI, and close/positive margin were associated with poor OS. LVI emerged as a key factor affecting both DMFS and OS, with a 5-year OS of 93.3% for patients without LVI compared to 35.8% with LVI. Based on these factors, a nomogram predicting 3-year and 5-year DMFS and OS was developed, demonstrating high concordance with actual survival in the cohort (Harrell C-index 0.809 for OS, 0.801 for DMFS, respectively).
Conclusion
The prognosis of cHCC-CCA is notably poor when combined with LVI. Given the significant impact of adverse features, accurate outcome prediction is crucial. Moreover, consideration of adjuvant therapy may be warranted for patients exhibiting poor survival and increased risk of local recurrence or distant metastasis.

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Combined hepatocellular-cholangiocarcinoma in a middle-aged patient: A case report and review of therapeutic approaches
Chen Guo, Yutao He, Zhitian Shi, Lin Wang
International Journal of Surgery Case Reports.2025; 129: 111165. CrossRef

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Prognostic Significance of Bulky Nodal Disease in Anal Cancer Management: A Multi-institutional Study: Seok-Joo Chun, Eunji Kim, Won Il Jang, Mi-Sook Kim, Hyun-Cheol Kang, Byoung Hyuck Kim, Eui Kyu Chie; Cancer Res Treat. 2024;56(4):1197-1206. Published online April 11, 2024; DOI: https://doi.org/10.4143/crt.2024.258

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to assess the prognostic significance of bulky nodal involvement in patients with anal squamous cell carcinoma treated with definitive chemoradiotherapy.
Materials and Methods
We retrospectively analyzed medical records of patients diagnosed with anal squamous cell carcinoma who underwent definitive chemoradiotherapy at three medical centers between 2004 and 2021. Exclusion criteria included distant metastasis at diagnosis, 2D radiotherapy, and salvage treatment for local relapse. Bulky N+ was defined as nodes with a long diameter of 2 cm or greater.
Results
A total of 104 patients were included, comprising 51 with N0, 46 with non-bulky N+, and seven with bulky N+. The median follow-up duration was 54.0 months (range, 6.4 to 162.2 months). Estimated 5-year progression-free survival (PFS), loco-regional recurrence-free survival (LRRFS), and overall survival (OS) rates for patients with bulky N+ were 42.9%, 42.9%, and 47.6%, respectively. Bulky N+ was significantly associated with inferior PFS, LRRFS, and OS compared to patients without or with non-bulky N+, even after multivariate analysis. We proposed a new staging system incorporating bulky N+ as N2 category, with estimated 5-year LRRFS, PFS, and OS rates of 81.1%, 80.6%, and 86.2% for stage I, 67.7%, 60.9%, and 93.3% for stage II, and 42.9%, 42.9%, and 47.6% for stage III disease, enhancing the predictability of prognosis.
Conclusion
Patients with bulky nodal disease treated with standard chemoradiotherapy experienced poor survival outcomes, indicating the potential necessity for further treatment intensification.

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MR Imaging of Anal Cancer
Josip Nincevic, Gaiane M. Rauch, Jennifer S. Golia Pernicka
Radiologic Clinics of North America.2025; 63(3): 435. CrossRef

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Breast cancer

Assessment of Eligibility and Utilization of Accelerated Partial Breast Irradiation in Korean Breast Cancer Patients (KROG 22-15): Seok-Joo Chun, Ji Hwan Jo, Yong Bae Kim, Sangjoon Park, Sung-Ja Ahn, Su Ssan Kim, Kyubo Kim, Kyung Hwan Shin; Cancer Res Treat. 2024;56(2):549-556. Published online December 8, 2023; DOI: https://doi.org/10.4143/crt.2023.1109

Abstract PDF Supplementary Material PubReader ePub

Purpose
We investigated the proportions of patients eligible for accelerated partial breast irradiation (APBI) among those with pT1-2N0 breast cancer, based on the criteria set by the American Society for Radiation Oncology (ASTRO), the Groupe Européen de Curiethérapie and the European Society for Radiotherapy and Oncology (GEC-ESTRO), the American Brachytherapy Society (ABS), and the American Society of Breast Surgeons (ASBS). Additionally, we analyzed the rate of APBI utilization among eligible patients.
Materials and Methods
Patients diagnosed with pT1-2N0 breast cancer in 2019 were accrued in four tertiary medical centers in Korea. All patients had undergone breast conserving surgery followed by radiotherapy, either whole breast irradiation or APBI. To determine which guideline best predicts the use of APBI in Korea, the F1 score and Matthews Correlation Coefficient (MCC) were determined for each guideline.
Results
A total of 1,251 patients were analyzed, of whom 196 (15.7%) underwent APBI. The percentages of eligible patients identified by the ASTRO, GEC-ESTRO, ABS, and ASBS criteria were 13.7%, 21.0%, 50.5%, and 63.5%, respectively. APBI was used to treat 54.4%, 37.2%, 27.1%, and 23.7% of patients eligible by the ASTRO, GEC-ESTRO, ABS, and ASBS criteria, respectively. The ASTRO guideline exhibited the highest F1 score (0.76) and MCC (0.67), thus showing the best prediction of APBI utilization in Korea.
Conclusion
The proportion of Korean breast cancer patients who are candidates for APBI is substantial. The actual rate of APBI utilization among eligible patients may suggest there is a room for risk-stratified optimization in offering radiation therapy.

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Impact of the ASTRO 2024 Guideline on Partial Breast Irradiation Eligibility in Breast Cancer Patients (KROG 24-01)
Seok-Joo Chun, Sangjoon Park, Yong Bae Kim, Sung-Ja Ahn, Kyubo Kim, Kyung Hwan Shin
Practical Radiation Oncology.2025; 15(3): e230. CrossRef

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