Cancer Research and Treatment

Relationships between the Microbiome and Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer: Hye In Lee, Bum-Sup Jang, Ji Hyun Chang, Eunji Kim, Tae Hoon Lee, Jeong Hwan Park, Eui Kyu Chie; Received June 2, 2024 Accepted December 13, 2024 Published online December 16, 2024; DOI: https://doi.org/10.4143/crt.2024.521 [Accepted]

Abstract PDF: Purpose
This study aimed to investigate the dynamic changes in the microbiome of patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy (nCRT), focusing on the relationship between the microbiome and response to nCRT.
Materials and Methods
We conducted a longitudinal study involving 103 samples from 26 patients with LARC. Samples were collected from both the tumor and normal rectal tissues before and after nCRT. Diversity, taxonomic, and network analyses were performed to compare the microbiome profiles across different tissue types, pre- and post-nCRT time-points, and nCRT responses.
Results
Between the tumor and normal tissue samples, no differences in microbial diversity and composition were observed. However, when pre- and post-nCRT samples were compared, there was a significant decrease in diversity, along with notable changes in composition. Non-responders exhibited more extensive changes in their microbiome composition during nCRT, characterized by an increase in pathogenic microbes. Meanwhile, responders had relatively stable microbiome communities with more enriched butyrate-producing bacteria. Network analysis revealed distinct patterns of microbial interactions between responders and non-responders, where butyrate-producing bacteria formed strong networks in responders, while opportunistic pathogens formed strong networks in non-responders. A Bayesian network model for predicting the nCRT response was established, with butyrate-producing bacteria playing a major predictive role.
Conclusion
Our study demonstrated a significant association between the microbiome and nCRT response in LARC patients, leading to the development of a microbiome-based response prediction model. These findings suggest potential applications of microbiome signatures for predicting and optimizing nCRT treatment in LARC patients.

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Normal Brain-Sparing Radiotherapy versus Whole Brain Radiotherapy for Multiple Brain Metastasis from Non-Small Cell Lung Cancer: Sangjoon Park, Jaeho Cho, Kyung Hwan Kim, Hong In Yoon, Chang Geol Lee; Received July 23, 2024 Accepted December 2, 2024 Published online December 3, 2024; DOI: https://doi.org/10.4143/crt.2024.679 [Accepted]

Abstract PDF: Purpose
The efficacy and lower neurotoxicity of normal brain-sparing radiotherapy (NBS-RT) with systemic therapy in treating multiple brain metastases from non-small cell lung cancer (NSCLC) is underexplored. This study compares whole-brain radiotherapy (WBRT) and NBS-RT for multiple brain metastases in NSCLC, focusing on treatment outcomes and leukoencephalopathy.
Materials and Methods
This retrospective study included 503 patients with NSCLC with multiple brain metastases at a single center, treated with either WBRT or NBS-RT. Post-RT treatments included chemotherapy, targeted therapy, or immunotherapy. Main outcomes measured were intracranial control, overall survival (OS), and leukoencephalopathy incidence.
Results
In this study, 441 patients received WBRT and 62 received NBS-RT, with median ages of 62 and 61 years, respectively. A significant portion of both groups, 77.3% in WBRT and 80.6% in NBS-RT, received post-RT systemic therapy. The median number of brain metastases was 10 for WBRT and 12 for NBS-RT, with median maximal diameters of 11.7 mm in WBRT and 14.4 mm in NBS-RT. After a median follow-up of 10.9 months for WBRT and 11.8 months for NBS-RT, there were no significant differences in intracranial progression (p=0.516) or OS (p=0.492) between the groups. However, WBRT patients had a higher incidence of leukoencephalopathy than NBS-RT patients (p=0.013).
Conclusion
NBS-RT combined with systemic therapy was as effective in treating multiple brain metastases as WBRT and was less toxic. NBS-RT-based strategies deserve further investigation in a prospective setting.

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To Use or Not to Use: Temozolomide in Elderly Patients with IDH Wild-type MGMT Promoter Unmethylated Glioblastoma Treated with Radiotherapy: Chan Woo Wee, Joo Ho Lee, Hye In Lee, Jina Kim, Jong Hee Chang, Seok-Gu Kang, Eui Hyun Kim, Ju Hyung Moon, Jaeho Cho, Chul-Kee Park, Chae-Yong Kim, Kihwan Hwang, Hong In Yoon, In Ah Kim; Received September 27, 2024 Accepted November 9, 2024 Published online November 11, 2024; DOI: https://doi.org/10.4143/crt.2024.945 [Accepted]

Abstract PDF: Purpose
To identify a specific subgroup of patients among elderly glioblastoma patients aged 70 years or older with unmethylated MGMT promoters (eGBM-unmethylated) who would significantly benefit from the addition of temozolomide (TMZ) to radiotherapy (RT).
Materials and Methods
Newly diagnosed patients with IDH wild-type eGBM-unmethylated treated with RT were included in this multicenter analysis (n=182). RT dose was 45 Gy in 15 fractions (62.3%), 60 Gy in 30 fractions, or 61.2 Gy in 34 fractions. For patients treated with RT plus TMZ (60.4%), TMZ was administered concurrently with RT, followed by six adjuvant cycles. The primary endpoint was overall survival.
Results
During a median follow-up of 11.3 months for survivors, the median survival was 12.2 months. The median survival duration significantly improved with the addition of TMZ to RT compared with that with RT alone (13.6 months vs. 10.5 months, p=0.028). In the multivariable analysis adjusted for clinical, radiological, and genetic biomarkers, the addition of TMZ significantly improved overall survival (hazard ratio, 0.459; p=0.006). In subgroup analysis, median survival was especially improved by 4–5 months in patients with residual disease (p<0.001), Karnofsky Performance Status ≥60 (p=0.033), and age ≤75 years (p=0.090). A significant benefit of TMZ was noted only in patients with two or three of the above factors (median survival, 14.1 months vs. 10.5 months, p=0.014).
Conclusion
The addition of TMZ significantly improved the survival of patients with eGBM-unmethylated treated with RT. The suggested criteria for the specific subgroup in these patients warrant external validation for clinical application.

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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 [Accepted]

Abstract PDF: Purpose
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 (SABR) 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 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 RT (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, IFN‒γ, and TNF‒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 anti-tumor immune responses.

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Unraveling the Impact of Sarcopenia-Induced Lymphopenia on Treatment Response and Prognosis in Patients with Stage III Non-Small Cell Lung Cancer: Insights for Optimizing Chemoradiation and Immune Checkpoint Inhibitor: Joongyo Lee, Kyung Hwan Kim, Jina Kim, Chang Geol Lee, Jaeho Cho, Hong In Yoon, Yeona Cho; Received May 23, 2024 Accepted October 29, 2024 Published online October 30, 2024; DOI: https://doi.org/10.4143/crt.2024.493 [Accepted]

Abstract PDF: Purpose
Sarcopenia is a poor prognostic factor in non-small cell lung cancer (NSCLC). However, its prognostic significance in patients with NSCLC receiving immune checkpoint inhibitors (ICIs) and its relationship with lymphopenia remain unclear. We aimed to investigate the prognostic role of sarcopenia and its effect on lymphocyte recovery in patients with stage III NSCLC treated with concurrent chemoradiotherapy (CCRT) followed by ICI.
Materials and Methods
We retrospectively evaluated 151 patients with stage III NSCLC who received definitive CCRT followed by maintenance ICI between January 2016 and June 2022. Sarcopenia was evaluated by measuring the skeletal muscle area at the L3 vertebra level using computed tomography scans. Lymphocyte level changes were assessed based on measurements taken before and during CCRT and at 1, 2, 3, 6, and 12 months post-CCRT completion.
Results
Even after adjusting for baseline absolute lymphocyte count through propensity score-matching, patients with pre-radiotherapy (RT) sarcopenia (n=86) exhibited poor lymphocyte recovery and a significantly high incidence of grade ≥3 lymphopenia during CCRT. Pre-RT sarcopenia and grade ≥3 lymphopenia during CCRT emerged as prognostic factors for overall survival and progression-free survival, respectively. Concurrent chemotherapy dose adjustments, objective response after CCRT, and discontinuation of maintenance ICI were also analyzed as independent prognostic factors.
Conclusion
Our results demonstrated an association between pre-RT sarcopenia and poor survival, concurrent chemotherapy dose adjustments, and impaired lymphocyte recovery after definitive CCRT. Moreover, CCRT-induced lymphopenia not only contributed to poor prognosis but may have also impaired the therapeutic efficacy of subsequent maintenance ICI, ultimately worsening treatment outcomes.

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Choosing Wisely between Radiotherapy Dose-Fractionation Schedules: The Molecular Graded Prognostic Assessment for Elderly Glioblastoma Patients: Hye In Lee, Jina Kim, In Ah Kim, Joo Ho Lee, Jaeho Cho, Rifaquat Rahman, Geoffrey Fell, Chan Woo Wee, Hong In Yoon; Received July 22, 2024 Accepted September 10, 2024 Published online September 11, 2024; DOI: https://doi.org/10.4143/crt.2024.680 [Epub ahead of print]

Abstract PDF Supplementary Material: Purpose
This study aimed to develop a graded prognostic assessment (GPA) model integrating genomic characteristics for elderly patients with glioblastoma (eGBM), and to compare the efficacy of different radiotherapy schedules.
Materials and Methods
This multi-institutional retrospective study included patients aged ≥ 65 years who underwent surgical resection followed by radiotherapy with or without temozolomide (TMZ) for newly diagnosed eGBM. Based on the significant factors identified in the multivariate analysis for overall survival (OS), the molecular GPA for eGBM (eGBM-molGPA) was established.
Results
A total of 334 and 239 patients who underwent conventionally fractionated radiotherapy (CFRT) and hypofractionated radiotherapy (HFRT) were included, respectively, with 86% of patients receiving TMZ-based chemoradiation. With a median follow-up of 17.4 months (range, 3.3 to 149.9 months), the median OS was 18.7 months for CFRT+TMZ group, 15.1 months for HFRT+TMZ group, and 10.4 months for radiotherapy alone group (CFRT+TMZ vs. HFRT+TMZ: hazard ratio [HR], 1.52; p < 0.001 and CFRT+TMZ vs. radiotherapy alone: HR, 2.52; p < 0.001). In a combined analysis with the NOA-08 and Nordic trials, CFRT+TMZ group exhibited the highest survival rates among all treatment groups. The eGBM-molGPA, which integrated four clinical and three molecular parameters, stratified patients into low-, intermediate-, and high-risk groups. CFRT+TMZ significantly improved OS compared to HFRT+TMZ or radiotherapy alone in the low-risk (p=0.023) and intermediate-risk groups (p < 0.001). However, in the high-risk group, there was no significant difference in OS between treatment options (p=0.770).
Conclusion
CFRT+TMZ may be more effective than HFRT+TMZ or radiotherapy alone for selected eGBM patients. The novel eGBM-molGPA model can guide treatment selection for this patient population.

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Gastrointestinal cancer

Salvage Radiotherapy for Loco-regional Recurrence of Esophageal Cancer Following Surgery: Won Kyung Cho, Jae Myoung Noh, Dongryul Oh, Yong Chan Ahn, Jong-Mu Sun, Hong Kwan Kim, Young Mog Shim; Cancer Res Treat. 2025;57(1):165-173. Published online July 26, 2024; DOI: https://doi.org/10.4143/crt.2024.191

Abstract PDF Supplementary Material PubReader ePub: Purpose
There is few evidence regarding the optimal salvage treatment options for loco-reginal recurrence of esophageal cancer. This study aimed to evaluate the clinical outcomes of salvage radiotherapy (RT) in patients with loco-regional recurrence (LRR) after surgery for esophageal cancer.
Materials and Methods
We retrospectively reviewed 147 esophageal cancer patients who received salvage RT for loco-regional recurrence between 1996 and December 2019. A total dose of 60 Gy in 20 fractions was used for RT alone and 60-70 Gy in 30-35 fractions for concurrent chemoradiotherapy (CCRT).
Results
The patients’ median age was 65 years (range, 41 to 86 years). The median disease-free interval was 13.5 months (1.0 to 97.4 months). After a median 18.8 months follow-up, the 2-year overall survival (OS) and progression-free survival (PFS) rates were 38.1% and 25.9%, respectively. The median OS and PFS were 18.8 and 8.4 months, respectively. The CCRT could not improve OS compared to RT (p=0.336), but there was a trend of better PFS in the CCRT group. Regarding toxicities, the rate of grade 3 or higher toxicity was 10.9% occurring in 16 patients, and it was higher in patients who received CCRT than in the RT alone group (19.6% vs. 6.3%, p=0.023).
Conclusion
Salvage RT alone as well as CCRT could be effective in patients with locoregionally recurrent esophageal cancer.

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Breast cancer

Locoregional Recurrence in Adenoid Cystic Carcinoma of the Breast: A Retrospective, Multicenter Study (KROG 22-14): Sang Min Lee, Bum-Sup Jang, Won Park, Yong Bae Kim, Jin Ho Song, Jin Hee Kim, Tae Hyun Kim, In Ah Kim, Jong Hoon Lee, Sung-Ja Ahn, Kyubo Kim, Ah Ram Chang, Jeanny Kwon, Hae Jin Park, Kyung Hwan Shin; Cancer Res Treat. 2025;57(1):150-158. Published online July 12, 2024; DOI: https://doi.org/10.4143/crt.2024.201

Abstract PDF PubReader ePub: Purpose
This study aims to evaluate the treatment approaches and locoregional patterns for adenoid cystic carcinoma (ACC) in the breast, which is an uncommon malignant tumor with limited clinical data.
Materials and Methods
A total of 93 patients diagnosed with primary ACC in the breast between 1992 and 2022 were collected from multi-institutions. All patients underwent surgical resection, including breast-conserving surgery (BCS) or total mastectomy (TM). Recurrence patterns and locoregional recurrence-free survival (LRFS) were assessed.
Results
Seventy-five patients (80.7%) underwent BCS, and 71 of them (94.7%) received post-operative radiation therapy (PORT). Eighteen patients (19.3%) underwent TM, with five of them (27.8%) also receiving PORT. With a median follow-up of 50 months, the LRFS rate was 84.2% at 5 years. Local recurrence (LR) was observed in five patients (5.4%) and four cases (80%) of the LR occurred in the tumor bed. Three of LR (3/75, 4.0%) had a history of BCS and PORT, meanwhile, two of LR (2/18, 11.1%) had a history of mastectomy. Regional recurrence occurred in two patients (2.2%), and both cases had a history of PORT with (n=1) and without (n=1) irradiation of the regional lymph nodes. Partial breast irradiation (p=0.35), BCS (p=0.96) and PORT in BCS group (p=0.33) had no significant association with LRFS.
Conclusion
BCS followed by PORT was the predominant treatment approach for ACC of the breast and LR mostly occurred in the tumor bed. The findings of this study suggest that partial breast irradiation might be considered for PORT in primary breast ACC.

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Role of HIF-1α in the Responses of Tumors to Radiotherapy and Chemotherapy: Chang W Song, Hyunkyung Kim, Mi-Sook Kim, Heon J Park, Sun-Ha Paek, Stephanie Terezakis, L Chinsoo Cho; Cancer Res Treat. 2025;57(1):1-10. Published online June 5, 2024; DOI: https://doi.org/10.4143/crt.2024.255

Abstract PDF PubReader ePub: Tumor microenvironment is intrinsically hypoxic with abundant hypoxia-inducible factors-1α (HIF-1α), a primary regulator of the cellular response to hypoxia and various stresses imposed on the tumor cells. HIF-1α increases radioresistance and chemoresistance by reducing DNA damage, increasing repair of DNA damage, enhancing glycolysis that increases antioxidant capacity of tumors cells, and promoting angiogenesis. In addition, HIF-1α markedly enhances drug efflux, leading to multidrug resistance. Radiotherapy and certain chemotherapy drugs evoke profound anti-tumor immunity by inducing immunologic cell death that release tumor-associated antigens together with numerous pro-immunological factors, leading to priming of cytotoxic CD8+ T cells and enhancing the cytotoxicity of macrophages and natural killer cells. Radiotherapy and chemotherapy of tumors significantly increase HIF-1α activity in tumor cells. Unfortunately, HIF-1α effectively promotes various immune suppressive pathways including secretion of immune suppressive cytokines, activation of myeloid-derived suppressor cells, activation of regulatory T cells, inhibition of T cells priming and activity, and upregulation of immune checkpoints. Consequently, the anti-tumor immunity elevated by radiotherapy and chemotherapy is counterbalanced or masked by the potent immune suppression promoted by HIF-1α. Effective inhibition of HIF-1α may significantly increase the efficacy of radiotherapy and chemotherapy by increasing radiosensitivity and chemosensitivity of tumor cells and also by upregulating anti-tumor immunity.

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Lung and Thoracic cancer

Adjuvant Pembrolizumab in Patients with Stage IIIA/N2 Non–Small Cell Lung Cancer Completely Resected after Neoadjuvant Concurrent Chemoradiation: A Prospective, Open-Label, Single-Arm, Phase 2 Trial: Junghoon Shin, Sehhoon Park, Kyung Hwan Kim, Eui-Cheol Shin, Hyun Ae Jung, Jong Ho Cho, Jong-Mu Sun, Se-Hoon Lee, Yong Soo Choi, Jin Seok Ahn, Jhingook Kim, Keunchil Park, Young Mog Shim, Hong Kwan Kim, Jae Myoung Noh, Yong Chan Ahn, Hongryull Pyo, Myung-Ju Ahn; Cancer Res Treat. 2024;56(4):1084-1095. Published online April 30, 2024; DOI: https://doi.org/10.4143/crt.2024.084

Abstract PDF Supplementary Material PubReader ePub: Purpose
Optimal treatment for stage IIIA/N2 non–small cell lung cancer (NSCLC) is controversial. We aimed to assess the efficacy and safety of adjuvant pembrolizumab for stage IIIA/N2 NSCLC completely resected after neoadjuvant concurrent chemoradiation therapy (CCRT).
Materials and Methods
In this open-label, single-center, single-arm phase 2 trial, patients with stage IIIA/N2 NSCLC received adjuvant pembrolizumab for up to 2 years after complete resection following neoadjuvant CCRT. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety. As an exploratory biomarker analysis, we evaluated the proliferative response of blood CD39⁺PD-1⁺CD8⁺ T cells using fold changes in the percentage of proliferating Ki-67⁺ cells from days 1 to 7 of cycle 1 (Ki-67_D7/D1).
Results
Between October 2017 and October 2018, 37 patients were enrolled. Twelve (32%) and three (8%) patients harbored EGFR and ALK alterations, respectively. Of 34 patients with programmed cell death ligand 1 assessment, 21 (62%), nine (26%), and four (12%) had a tumor proportion score of < 1%, 1%-50%, and ≥ 50%, respectively. The median follow-up was 71 months. The median DFS was 22.4 months in the overall population, with a 5-year DFS rate of 29%. The OS rate was 86% at 2 years and 76% at 5 years. Patients with tumor recurrence within 6 months had a significantly lower Ki-67D7/D1 among CD39⁺PD-1⁺CD8⁺ T cells than those without (p=0.036). No new safety signals were identified.
Conclusion
Adjuvant pembrolizumab may offer durable disease control in a subset of stage IIIA/N2 NSCLC patients after neoadjuvant CCRT and surgery.

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Gastrointestinal cancer

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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Genitourinary cancer

Neoadjuvant Cisplatin-Based Chemotherapy Followed by Selective Bladder Preservation Chemoradiotherapy in Muscle-Invasive Urothelial Carcinoma of the Bladder: Post Hoc Analysis of Two Prospective Studies: Sung Wook Cho, Sung Hee Lim, Ghee Young Kwon, Chan Kyo Kim, Won Park, Hongryull Pyo, Jae Hoon Chung, Wan Song, Hyun Hwan Sung, Byong Chang Jeong, Se Hoon Park; Cancer Res Treat. 2024;56(3):893-897. Published online February 15, 2024; DOI: https://doi.org/10.4143/crt.2024.015

Abstract PDF PubReader ePub

Purpose
Bladder preservation chemoradiotherapy (CRT) in patients with a clinical complete response (cCR) following cisplatin-based neoadjuvant chemotherapy (NAC) is a promising treatment strategy for muscle-invasive bladder urothelial carcinoma (MIBC). A combined analysis of raw data from two prospective phase II studies was performed to better evaluate the feasibility of selective bladder preservation CRT.
Materials and Methods
The analysis was based on primary efficacy data from two independent studies, including 76 MIBC patients receiving NAC followed by bladder preservation CRT. The efficacy data included metastasis-free survival (MFS) and disease-free survival (DFS). For the present analysis, starting point of survival was defined as the date of commencing CRT.
Results
Among 76 patients, 66 had a cCR following NAC. Sixty-four patients received gemcitabine and cisplatin (GC) combination chemotherapy in neoadjuvant setting, and 12 received nivolumab plus GC. Bladder preservation CRT following NAC was generally well-tolerated, with low urinary tract symptoms being the most common late complication. With a median follow-up of 64 months, recurrence was recorded in 43 patients (57%): intravesical only (n=20), metastatic only (n=16), and both (n=7). In 27 patients with intravesical recurrence, transurethral resection, and Bacillus Calmette-Guerin treatment was given to 17 patients. Salvage cystectomy was performed in 10 patients. Median DFS was 46.3 (95% confidence interval [CI], 25.1 to 67.5) months, and the median MFS was not reached. Neither DFS nor MFS appeared to be affected by any of the baseline characteristics. However, DFS was significantly longer in patients with a cCR than in those without (hazard ratio, 0.465; 95% CI, 0.222 to 0.976).
Conclusion
The strategy of NAC followed by selective bladder preservation CRT based on the cCR is feasible in the treatment of MIBC. A standardized definition of cCR is needed to better assess disease status post-NAC.

Citations

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News and prospects on radiotherapy for bladder cancer: Is trimodal therapy becoming the gold standard?
Olivier Riou, Christophe Hennequin, Jonathan Khalifa, Paul Sargos
Cancer/Radiothérapie.2024; 28(6-7): 623. CrossRef

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1 Web of Science
1 Crossref

Lung and Thoracic cancer

Contribution of Enhanced Locoregional Control to Improved Overall Survival with Consolidative Durvalumab after Concurrent Chemoradiotherapy in Locally Advanced Non–Small Cell Lung Cancer: Insights from Real-World Data: Jeong Yun Jang, Si Yeol Song, Young Seob Shin, Ha Un Kim, Eun Kyung Choi, Sang-We Kim, Jae Cheol Lee, Dae Ho Lee, Chang-Min Choi, Shinkyo Yoon, Su Ssan Kim; Cancer Res Treat. 2024;56(3):785-794. Published online January 16, 2024; DOI: https://doi.org/10.4143/crt.2023.1014

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to assess the real-world clinical outcomes of consolidative durvalumab in patients with unresectable locally advanced non–small cell lung cancer (LA-NSCLC) and to explore the role of radiotherapy in the era of immunotherapy.
Materials and Methods
This retrospective study assessed 171 patients with unresectable LA-NSCLC who underwent concurrent chemoradiotherapy (CCRT) with or without consolidative durvalumab at Asan Medical Center between May 2018 and May 2021. Primary outcomes included freedom from locoregional failure (FFLRF), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS).
Results
Durvalumab following CCRT demonstrated a prolonged median PFS of 20.9 months (p=0.048) and a 3-year FFLRF rate of 57.3% (p=0.008), compared to 13.7 months and 38.8%, respectively, with CCRT alone. Furthermore, the incidence of in-field recurrence was significantly greater in the CCRT-alone group compared to the durvalumab group (26.8% vs. 12.4%, p=0.027). While median OS was not reached with durvalumab, it was 35.4 months in patients receiving CCRT alone (p=0.010). Patients positive for programmed cell death ligand 1 (PD-L1) expression showed notably better outcomes, including FFLRF, DMFS, PFS, and OS. Adherence to PACIFIC trial eligibility criteria identified 100 patients (58.5%) as ineligible. The use of durvalumab demonstrated better survival regardless of eligibility criteria.
Conclusion
The use of durvalumab consolidation following CCRT significantly enhanced locoregional control and OS in patients with unresectable LA-NSCLC, especially in those with PD-L1–positive tumors, thereby validating the role of durvalumab in standard care.

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Therapeutic effect of induction therapy including nab-paclitaxel followed by surgical resection for the patients with locally advanced non-small-cell lung cancer
Hidetaka Uramoto, Nozomu Motono, Shun Iwai
Journal of Cardiothoracic Surgery.2024;[Epub] CrossRef

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1 Crossref

Gastrointestinal cancer

Combined High-Dose Radiotherapy with Sequential Gemcitabine-Cisplatin Based Chemotherapy Increase the Resectability and Survival in Locally Advanced Unresectable Intrahepatic Cholangiocarcinoma: A Multi-institutional Cohort Study: Jung Ho Im, Jeong Il Yu, Tae Hyun Kim, Tae Gyu Kim, Jun Won Kim, Jinsil Seong; Cancer Res Treat. 2024;56(3):838-846. Published online January 2, 2024; DOI: https://doi.org/10.4143/crt.2023.886

Abstract PDF Supplementary Material PubReader ePub: Purpose
The locally advanced unresectable intrahepatic cholangiocarcinoma (ICC) has detrimental oncological outcomes. In this study, we aimed to investigate the efficacy of radiotherapy in patients with locally advanced unresectable ICC.
Materials and Methods
Between 2001 and 2021, 116 patients were identified through medical record who underwent radiotherapy for locally advanced unresectable ICC. The resectability of ICC is determined by the multidisciplinary team at each institution. Overall survival (OS) were analyzed using the Kaplan-Meier method, and prognostic factors were analyzed using the Cox proportional hazards model.
Results
The median equivalent radiotherapy dose in 2 Gy fractions (EQD2) was 52 Gy (range, 30 to 110 Gy). Forty-seven patients (40.5%) received sequential gemcitabine-cisplatin based chemotherapy (GEM-CIS CTx). Multivariate analysis identified two risk factors, EQD2 of ≥ 60 Gy and application of sequential GEM-CIS CTx for OS. Patients were grouped by these two risk factors: group 1, EQD2 ≥ 60 Gy with sequential GEM-CIS CTx (n=25); group 2, EQD2 < 60 Gy with sequential GEM-CIS CTx or fluoropyrimidine-based concurrent chemoradiotherapy (n=70); and group 3, radiotherapy alone (n=21). Curative resection was more frequently undergone in group 1 than in groups 2 or 3 (28% vs. 8.6% vs. 0%, respectively). Consequently, OS was significantly better in group 1 than in groups 2 and 3 (p < 0.05).
Conclusion
Combined high-dose radiotherapy with sequential GEM-CIS CTx improved oncologic outcomes in patients with locally advanced unresectable ICC. Further prospective studies are required to validate these findings.

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The Clinical Efficacy of Colorectal Cancer Patients with Pulmonary Oligometastases by Sterotactic Body Ablative Radiotherapy: A Meta-Analysis: Jae-Uk Jeong, Chai Hong Rim, Gyu Sang Yoo, Won Kyung Cho, Eui Kyu Chie, Yong Chan Ahn, Jong Hoon Lee, on behalf of Korean Oligometastasis Working Group, Korean Cancer Association; Cancer Res Treat. 2024;56(3):809-824. Published online December 14, 2023; DOI: https://doi.org/10.4143/crt.2023.920

Abstract PDF Supplementary Material PubReader ePub

Purpose
There is increasing interest in the efficacy of stereotactic ablative radiotherapy (SABR) for treating colorectal cancer (CRC) patients with oligometastases (OM), recently. The purpose of this meta-analysis was to evaluate local control (LC), progression-free survival (PFS), and overall survival (OS) of CRC patients with pulmonary OM treated with SABR and toxicities.
Materials and Methods
Studies that reported SABR for CRC patients with pulmonary OM were searched from MEDLINE and Embase. Treatment outcomes including LC, PFS, OS, and toxicities of grade 3 or higher were assessed.
Results
A total of 19 studies with 1,668 patients were chosen for this meta-analysis. Pooled 1-, 2-, and 3-year LC rates were 83.1%, 69.3%, and 63.9%, respectively. PFS rates were 44.8%, 26.5%, and 21.5% at 1, 2, and 3 years, respectively. OS rates at 1-, 2-, and 3-year were 87.5%, 69.9%, and 60.5%, respectively. The toxicity rate of grade 3 or higher was 3.6%. The effect of dose escalation was meta-analyzed using available studies.
Conclusion
Application of SABR to CRC patients with pulmonary OM achieved modest local control with acceptable toxicity according to the present meta-analysis. Further studies establishing the clinical efficacy of SABR are guaranteed.

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Identifying Trends in Oncology Research through a Bibliographic Analysis of Cancer Research and Treatment
Choong-kun Lee, Jeong Min Choo, Yong Chan Ahn, Jin Kim, Sun Young Rha, Chai Hong Rim
Cancer Research and Treatment.2025; 57(1): 11. 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

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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.2024;[Epub] CrossRef

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General

Radiation Oncologists’ Perspectives on Oligometastatic Disease: A Korean Survey Study: Chai Hong Rim, Won Kyung Cho, Jong Hoon Lee, Young Seok Kim, Yang-Gun Suh, Kyung Hwan Kim, Ah Ram Chang, Eui Kyu Chie, Yong Chan Ahn, on behalf of the Oligometastasis Working Group, Korean Cancer Association; Cancer Res Treat. 2024;56(2):414-421. Published online November 22, 2023; DOI: https://doi.org/10.4143/crt.2023.876

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Purpose
Perspectives of radiation oncologists on oligometastatic disease was investigated using multi-layered survey.
Materials and Methods
Online survey on the oligometastatic disease was distributed to the board-certified regular members of the Korean Society for Radiation Oncology. The questionnaire consisted of four domains: five questions on demographics; five on the definition of oligometastatic disease; four on the role of local therapy; and three on the oligometastatic disease classification, respectively.
Results
A total of 135 radiation oncologists participated in the survey. The median length of practice after board certification was 22.5 years (range, 1 to 44 years), and the vast majority (94.1%) answered affirmatively to the clinical experience in oligometastatic disease management. Nearly two-thirds of the respondents considered the number of involved organs as an independent factor in defining oligometastasis. Most frequently perceived upper limit on the numerical definition of oligometastasis was 5 (64.2%), followed by 3 (26.0%), respectively. Peritoneal and brain metastasis were nominated as the sites to be excluded from oligometastastic disease by 56.3% and 12.6% of the participants, respectively. Vast majority (82.1%) agreed on the role of local treatment in the management of oligometastatic disease. Majority (72%) of the participants acknowledged the European Society for Radiotherapy and Oncology (ESTRO)–European Organisation for Research and Treatment of Cancer (EORTC) classification of oligometastatic disease, however, only 43.3% answered that they applied this classification in their clinical practice. Underlying reasons against the clinical use were ‘too complicated’ (66.0%), followed by ‘insufficient supporting evidence’ (30.0%), respectively.
Conclusion
While most radiation oncologists supported the role of local therapy in oligometastatic disease, there were several inconsistencies in defining and categorizing oligometastatic disease. Continued education and training on oligometastatic disease would be also required to build consensus among participating caregivers.

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A new proposal of simplified classification of non-small cell lung cancer oligometastases for easy applicability through systematic literature analysis and meta-analysis validation
Hanseung Kang, Woohyeon Do, Yong Chan Ahn, Eui Kyu Chie, Chai Hong Rim
European Journal of Cancer.2024; 212: 115043. CrossRef

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Breast cancer

Implication of Pre- and Post-radiotherapy ctDNA Dynamics in Patients with Residual Triple-Negative Breast Cancer at Surgery after Neoadjuvant Chemotherapy: Findings from a Prospective Observational Study: Tae Hoon Lee, Haeyoung Kim, Yeon Jeong Kim, Woong-Yang Park, Won Park, Won Kyung Cho, Nalee Kim; Cancer Res Treat. 2024;56(2):531-537. Published online November 10, 2023; DOI: https://doi.org/10.4143/crt.2023.996

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Purpose
This study aims to determine the association between pre- and postoperative radiotherapy (PORT) circulating tumor DNA (ctDNA) dynamics and oncological outcomes in patients with residual triple-negative breast cancer who underwent surgery after neoadjuvant chemotherapy (NAC).
Materials and Methods
Between March 2019 and July 2020, 11 nonmetastatic patients with residual disease who underwent surgery after NAC were prospectively enrolled. In each patient, tumor specimens obtained during surgery and blood samples collected at three time points during PORT (T0: pre-PORT, T1: 3 weeks after PORT, T2: 1 month after PORT) were sequenced, targeting 38 cancer-related genes. Disease-free survival (DFS) was evaluated and the association between DFS and ctDNA dynamics was analyzed.
Results
At T0, ctDNA was detected in three (27.2%) patients. The ctDNA dynamics were as follows: two showed a decreasing ctDNA variant allele frequency (VAF) and reached zero VAF at T2, while one patient exhibited an increasing VAF during PORT and maintained an elevated VAF at T2. After a median follow-up of 48 months, two patients experienced distant metastasis without any locoregional failures. All failures occurred in patients with ctDNA positivity at T0 and a decreased VAF after PORT. The 4-year DFS rates according to the T0 ctDNA status were 67% (positive ctDNA) and 100% (negative ctDNA) (p=0.032).
Conclusion
More than a quarter of the patients with residual disease after post-NAC surgery exhibited pre-PORT ctDNA positivity, and ctDNA positivity was associated with poor DFS. For patients with pre-PORT ctDNA positivity, the administration of a more effective systemic treatment should be considered.

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Multiple drugs

Reactions Weekly.2024; 2033(1): 183. CrossRef

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Lung and Thoracic cancer

Intrathoracic Progression Is Still the Most Dominant Failure Pattern after First-Line Chemo-immunotherapy in Extensive-Stage Small-Cell Lung Cancer: Implications for Thoracic Radiotherapy: Dowook Kim, Hak Jae Kim, Hong-Gyun Wu, Joo Ho Lee, Suzy Kim, Tae Min Kim, Jin-Soo Kim, Byoung Hyuck Kim; Cancer Res Treat. 2024;56(2):430-441. Published online November 6, 2023; DOI: https://doi.org/10.4143/crt.2023.931

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Purpose
This study aimed to compare the failure patterns before and after the introduction of immunotherapy and to determine the role of thoracic radiotherapy (TRT) in extensive-stage small-cell lung cancer (ES-SCLC) treatment.
Materials and Methods
We retrospectively reviewed 294 patients with ES-SCLC, of which 62.2% underwent chemotherapy alone, 13.3% underwent chemotherapy followed by consolidative TRT (TRT group), and 24.5% underwent chemotherapy with immune checkpoint inhibitor (ICI group). We performed propensity-score matching (PSM) to compare each treatment group.
Results
The median follow-up duration was 10.4 months. At the first relapse, in the cohort showing objective response, the proportion of cases showing intrathoracic progression was significantly lower in the TRT group (37.8%) than in the chemotherapy-alone (77.2%, p < 0.001) and the ICI (60.3%, p=0.03) groups. Furthermore, in the subgroup analysis, TRT showed benefits related to intrathoracic progression-free survival (PFS) in comparison with ICI in patients with less than two involved extrathoracic sites (p=0.008) or without liver metastasis (p=0.02) or pleural metastasis (p=0.005) at diagnosis. After PSM, the TRT group showed significantly better intrathoracic PFS than both chemotherapy-alone and ICI groups (p < 0.001 and p=0.04, respectively), but showed no significant benefit in terms of PFS and overall survival in comparison with the ICI group (p=0.17 and p=0.31, respectively).
Conclusion
In ES-SCLC, intrathoracic progression was the most dominant failure pattern after immunotherapy. In the era of chemoimmunotherapy, consolidative TRT can still be considered a useful treatment strategy for locoregional control.

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Clinical outcomes and synergistic effect between radiotherapy and immunotherapy in patients with extensive-stage small cell lung cancer: a real-world study
Meiling Sun, Huaijun Ji, Fang Deng, Jingyi Li, Ning Xu, Yu Li
BMC Cancer.2024;[Epub] CrossRef

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Gastrointestinal cancer

NESC Multicenter Phase II Trial in the Preoperative Treatment of Gastric Adenocarcinoma with Chemotherapy (Docetaxel-Cisplatin-5FU+Lenograstim) Followed by Chemoradiation Based 5FU and Oxaliplatin and Surgery: Laurent Mineur, Frederi Plat, Françoise Desseigne, Gael Deplanque, Mohamed Belkacemi, Laurence Moureau-Zabotto, Carlos D. Beyrne, Khadija Jalali, Stéphane Obled, Denis Smith, Léa Vazquez, Rania Boustany; Cancer Res Treat. 2024;56(2):580-589. Published online October 5, 2023; DOI: https://doi.org/10.4143/crt.2023.812

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Purpose
Preoperative chemoradiation (CRT) is expected to increase the rate of curative resection and complete histological response. In this trial, we investigated the efficacy of a neoadjuvant CRT regimen in gastric adenocarcinoma (NCT01565109 trial).
Materials and Methods
Patients with stage IB to IIIC gastric adenocarcinoma, endoscopy ultrasound and computed tomography–scan diagnosed, were eligible for this phase II trial. Neoadjuvant treatment consisted of 2 cycles of chemotherapy with DCF (docetaxel, cisplatin, and 5-fluorouracil [5FU]) followed by preoperative CRT with oxaliplatin, continuous 5FU and radiotherapy (45 Gy in 25 fractions of 1.8 Gy, 5 fractions per week for 5 weeks) administered before surgery. R0-resection rate, pathological complete response (pathCR) rate, and survival (progression-free survival [PFS] and overall survival [OS]) were evaluated as primary endpoints.
Results
Among 33 patients included, 32 patients (97%) received CRT and 26 (78.8%) were resected (R0 resection for all patients resected). Among resected patients, we report pathCR in 23,1% and pathologic major response (tumor regression grade 2 according to Mandard’s classification) in 26,9%. With a median follow-up duration of 5.82 years (range, 0.4 to 9.24 years), the estimated median OS for all 33 patients was not reached; 1-, 3-, and 5-year OS rates were 85%, 61%, and 52%, respectively. Among resected patients, those whose histological response was tumor grade regression (TRG) 1-2 had significantly better OS and PFS rates than those with a TRG 3-4-5 response (p=0.019 and p=0.016, respectively).
Conclusion
Promising results from trials involving preoperative chemoradiation followed by surgery in gastric cancer need to be further evaluated in a phase III trial.

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Efficacy of Cisplatin-Containing Chemotherapy Regimens in Patients of Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-analysis
Obaid Ur Rehman, Eeshal Fatima, Zain Ali Nadeem, Arish Azeem, Jatin Motwani, Habiba Imran, Hadia Mehboob, Alishba Khan, Omer Usman
Journal of Gastrointestinal Cancer.2024; 55(2): 559. CrossRef
The Comparison of FLOT and DCF Regimens as Perioperative Treatment for Gastric Cancer
Gökhan Uçar, Serhat Sekmek, İrfan Karahan, Yakup Ergün, Özlem Aydın İsak, Sezai Tunç, Mutlu Doğan, Fatih Gürler, Doğan Bayram, Yusuf Açıkgöz, Selin Aktürk Esen , Burak Civelek, Fahriye Tuğba Köş , Öznur Bal, Efnan Algın, Tülay Eren, Gökşen İnanç İmamoğ
Oncology.2024; : 1. CrossRef

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Intensity-Modulated Radiation Therapy for Uterine Cervical Cancer to Reduce Toxicity and Enhance Efficacy – an Option or a Must?: A Narrative Review: Sea-Won Lee, Aeran Kim, Sung Jong Lee, Sung Hwan Kim, Jong Hoon Lee; Cancer Res Treat. 2024;56(1):1-17. Published online August 30, 2023; DOI: https://doi.org/10.4143/crt.2023.562

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Radiotherapy (RT) is a fundamental modality in treatment of cervical cancer. With advancement of technology, conventional RT used for external beam radiotherapy (EBRT) for over half a century has been rapidly replaced with intensity-modulated radiation therapy (IMRT) especially during the last decade. This newer technique is able to differentiate the intensity of radiation within the same field, thus reduces the inevitable exposure of radiation to normal organs and enables better dose delivery to tumors. Recently, the American Society for Radiation Oncology has released a guideline for RT in cervical cancer. Although a section of the guideline recommends IMRT for the purpose of toxicity reduction, a thorough review of the literature is necessary to understand the current status of IMRT in cervical cancer. This narrative review updates the recent high-level evidences regarding the efficacy and toxicity of IMRT and provides a better understanding of the most innovative techniques currently available for EBRT enabled by IMRT.

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Long term clinical outcomes of cervical cancer patients who were recommended surgery but did not undergo it: A SEER database study
Zhaoming Zhang, Hongfu Zhao, Guanghui Cheng
European Journal of Surgical Oncology.2024; 50(10): 108572. CrossRef
Treatment of secondary uterine malignancy following radiotherapy for cervical cancer: a study based on the SEER database
Xiaojing Tong, Yunyun Xiao, Haozhen Li, Hang Zhang, Jiawen Li
BMC Women's Health.2024;[Epub] CrossRef
Can knowledge-based planning models validated on ethnically diverse patients lead to global standardisation of external beam radiation therapy for locally advanced cervix cancer?
Jeevanshu Jain, Monica Serban, Marianne Sanggaard Assenholt, Varsha Hande, Jamema Swamidas, Yvette Seppenwoolde, Joanne Alfieri, Kari Tanderup, Supriya Chopra
Radiotherapy and Oncology.2024; : 110694. CrossRef

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Head and Neck cancer

Individualized Concurrent Chemotherapy for Patients with Stage III-IVa Nasopharyngeal Carcinoma Receiving Neoadjuvant Chemotherapy Combined with Definitive Intensity-Modulated Radiotherapy: Pengjie Ji, Qiongjiao Lu, Xiaoqiang Chen, Yuebing Chen, Xiane Peng, Zhiwei Chen, Cheng Lin, Shaojun Lin, Jingfeng Zong; Cancer Res Treat. 2023;55(4):1113-1122. Published online May 11, 2023; DOI: https://doi.org/10.4143/crt.2022.1651

Abstract PDF Supplementary Material PubReader ePub

Purpose
This retrospective study aimed to re-evaluate the effect of concurrent chemotherapy in patients with locally advanced nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiotherapy (IMRT).
Materials and Methods
A total of 498 patients who received neoadjuvant chemotherapy (NCT) combined with concurrent chemoradiotherapy (CCRT) or IMRT were retrospectively reviewed. The distribution of baseline characteristics was balanced using propensity score matching. Additionally, the results of NCT+IMRT and NCT+CCRT were compared using Kaplan-Meier survival analysis, and differences in survival rates were analyzed using the log rank test.
Results
There were no significant differences in overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and local progression-free survival (LRFS) between the two groups. Patients were further categorized into risk subgroups based on pretreatment Epstein-Barr virus (EBV) DNA cutoff values using receiver operating characteristic curve analysis. There were no statistically significant differences in OS, PFS, DMFS, and LRFS between patients who received NCT+CCRT and NCT+IMRT in the high-risk group. In the low-risk group, although there were no differences between NCT+CCRT and NCT+IMRT in OS, PFS, and LRFS, patients who received NCT+CCRT had better DMFS than those who received NCT+IMRT.
Conclusion
Pretreatment EBV DNA level can be used to individualize concurrent chemotherapy for patients with locally advanced NPC. Patients with low pretreatment EBV DNA levels may benefit from concurrent chemotherapy, whereas those with high levels may not. Other treatment modalities need to be explored for high-risk patients to improve their prognosis.

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Global trends in research of nasopharyngeal carcinoma: a bibliometric and visualization analysis
Guilin An, Jie Liu, Ting Lin, Lan He, Yingchun He
Frontiers in Oncology.2024;[Epub] CrossRef

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Metastasis-Directed Local Therapy of Hepatic Oligometastasis from Colorectal Cancer and Future Perspective in Radiation Therapy: Gyu Sang Yoo, Chai Hong Rim, Won Kyung Cho, Jae-Uk Jeong, Eui Kyu Chie, Hyeon-Min Cho, Jun Won Um, Yong Chan Ahn, Jong Hoon Lee, on behalf of Korean Cancer Association Oligometastasis Working Group; Cancer Res Treat. 2023;55(3):707-719. Published online March 15, 2023; DOI: https://doi.org/10.4143/crt.2022.1599

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Introduction of the concept for oligometastasis led to wide application of metastasis-directed local ablative therapies for metastatic colorectal cancer (CRC). By application of the metastasis-directed local ablative therapies including surgical resection, radiofrequency ablation (RFA), and stereotactic ablative body radiotherapy (SABR), the survival outcomes of patients with metastatic CRC have improved. The liver is the most common distant metastatic site in CRC patients, and recently various metastasis-directed local therapies for hepatic oligometastasis from CRC (HOCRC) are widely used. Surgical resection is the first line of metastatic-directed local therapy for HOCRC, but its eligibility is very limited. Alternatively, RFA can be applied to patients who are ineligible for surgical resection of liver metastasis. However, there are some limitations such as inferior local control (LC) compared with surgical resection and technical feasibility based on location, size, and visibility on ultrasonography of the liver metastasis. Recent advances in radiation therapy technology have led to an increase in the use of SABR for liver tumors. SABR is considered complementary to RFA for patients with HOCRC who are ineligible for RFA. Furthermore, SABR can potentially result in better LC for liver metastases > 2-3 cm compared with RFA. In this article, the previous studies regarding curative metastasis-directed local therapies for HOCRC based on the radiation oncologist’s and surgeon’s perspective are reviewed and discussed. In addition, future perspectives regarding SABR in the treatment of HOCRC are suggested.

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Identifying Trends in Oncology Research through a Bibliographic Analysis of Cancer Research and Treatment
Choong-kun Lee, Jeong Min Choo, Yong Chan Ahn, Jin Kim, Sun Young Rha, Chai Hong Rim
Cancer Research and Treatment.2025; 57(1): 11. CrossRef
Evidence-based clinical recommendations for hypofractionated radiotherapy: exploring efficacy and safety - Part 4: Liver and locally recurrent rectal cancer
Hwa Kyung Byun, Gyu Sang Yoo, Soo-Yoon Sung, Jin-Ho Song, Byoung Hyuck Kim, Yoo-Kang Kwak, Yeon Joo Kim, Yeon-Sil Kim, Kyung Su Kim
Radiation Oncology Journal.2024; 42(4): 247. CrossRef

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General

Recent Trends of Medical Expenses Associated with Radiation Therapy in Korea Based on HIRA Big Data: Jeong Eun Lee, Kyungmi Yang, Yong Chan Ahn, Won Park, Seung Jae Huh; Cancer Res Treat. 2023;55(3):758-765. Published online January 30, 2023; DOI: https://doi.org/10.4143/crt.2022.389

Abstract PDF Supplementary Material PubReader ePub

Purpose
We aimed to determine the trends in the use of radiotherapy (RT) and the expenses associated with it in South Korea.
Materials and Methods
The statistical data of the claims and reimbursement records provided on the Health and Insurance Review and Assessment Service website were utilized. This included information such as the number of patients, fractions, medical expenses according to treatment codes, in/outpatient, sex, age, and regions of hospitals. We analyzed data from 2016 to 2020.
Results
With a growing RT infrastructure and an increase in the number of radiation oncologists, the expenses for RT were 605.5 million USD in 2020, which had increased 1.5 times from 394.7 million USD in 2016. This growth was mainly because of the increased usage of advanced RT techniques. Furthermore, the proportion of intensity-modulated radiation therapy (IMRT) expenses in the total expenses increased by 1.6 times from 48.8% in 2016 to 76.9% in 2020. Advanced techniques were used more commonly in older individuals or children. However, the proportion of IMRT expenses increased mostly in young women. Additionally, geographical differences in RT use and expense were observed, although the gap in the IMRT fractions decreased among the regions.
Conclusion
Recent medical expenses associated with RT in Korea have increased in tandem with technological advances and changes in demographics.

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Large institutional experience of early outcomes and dosimetric findings with postoperative stereotactic partial breast irradiation in breast cancer
Jee Suk Chang, Jeongshim Lee, Frank A. Vicini, Jin Sung Kim, Jihun Kim, Seo Hee Choi, Ik Jae Lee, Yong Bae Kim
Radiotherapy and Oncology.2024; 191: 110066. CrossRef

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175 Download
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Lung and Thoracic cancer

Predictors of Post-chemoradiotherapy Pulmonary Complication in Locally Advanced Non–Small Cell Lung Cancer: Tae Hoon Lee, Byung-Hee Kang, Hak Jae Kim, Hong-Gyun Wu, Joo Ho Lee; Cancer Res Treat. 2023;55(3):865-874. Published online January 19, 2023; DOI: https://doi.org/10.4143/crt.2022.1538

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Purpose
We investigated the clinical effects and predictive factors of severe post-chemoradiotherapy pulmonary complications (PCPC) in locally advanced non–small cell lung cancer (LA-NSCLC).
Materials and Methods
Medical records of 317 patients who underwent definitive concurrent chemoradiation (CCRT) for LA-NSCLC were reviewed retrospectively. PCPC was defined as an event of admission or emergency department visit for acute or subacute pulmonary inflammatory complications, including pneumonitis and pneumonia, within 6 months after CCRT initiation. Patient characteristics, baseline lung function tests, radiation dosimetric parameters, and laboratory tests were analyzed to investigate their association with PCPC. Prognostic endpoints were disease progression rate (DPR) and overall survival (OS).
Results
PCPC was reported in 53 patients (16.7%). The OS of patients with PCPC was significantly worse (35.0% in 2 years) than that of patients without PCPC (67.0% in 2 years, p < 0.001). However, 2-year DPRs were 77.0% and 70.7% in patients with and without PCPC, respectively, which were not significantly different (p=0.087). In multivariate logistic regression, PCPC was independently associated with grade ≥ 1 hypoalbuminemia during CCRT (odds ratio [OR], 5.670; 95% confidence interval [CI], 2.487 to 13.40; p < 0.001), lower diffusing capacity of carbon monoxide (DLCO) (per mL/min/mmHg; OR, 0.855; 95% CI, 0.743 to 0.974; p=0.022), and higher lung V5 (per 10%; OR, 1.872; 95% CI, 1.336 to 2.699; p < 0.001).
Conclusion
PCPC might be a clinical endpoint to evaluate complications and predict the survival of patients subjected to CCRT for LA-NSCLC. Hypoalbuminaemia, DLCO, and lung V5 might predict PCPC in LA-NSCLC.

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Pneumonitis Risk After Chemoradiotherapy With and Without Immunotherapy in Patients With Locally Advanced Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis
Chong Han, Jingping Qiu, Lu Bai, Tingting Liu, Jun Chen, He Wang, Jun Dang
International Journal of Radiation Oncology*Biology*Physics.2024; 119(4): 1179. CrossRef
Prognostic Biomarkers of Systemic Inflammation in Non-Small Cell Lung Cancer: A Narrative Review of Challenges and Opportunities
Mark Stares, Leo R. Brown, Dhruv Abhi, Iain Phillips
Cancers.2024; 16(8): 1508. CrossRef
Comparison of post-chemoradiotherapy pneumonitis between Asian and non-Asian patients with locally advanced non-small cell lung cancer: a systematic review and meta-analysis
Tingting Liu, Sihan Li, Silu Ding, Jingping Qiu, Chengbo Ren, Jun Chen, He Wang, Xiaoling Wang, Guang Li, Zheng He, Jun Dang
eClinicalMedicine.2023; 64: 102246. CrossRef

3,580 View
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The Incidence and Risk Factors of Chronic Pulmonary Infection after Radiotherapy in Patients with Lung Cancer: Yeonseok Choi, Jae Myoung Noh, Sun Hye Shin, Kyungjong Lee, Sang-Won Um, Hojoong Kim, Hongryull Pyo, Yong Chan Ahn, Byeong-Ho Jeong; Cancer Res Treat. 2023;55(3):804-813. Published online January 3, 2023; DOI: https://doi.org/10.4143/crt.2022.1305

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Purpose
This study aimed to investigate cumulative incidence and risk factors associated with chronic pulmonary infection (CPI) development after radiotherapy for lung cancer.
Materials and Methods
We retrospectively analyzed 1,872 patients with lung cancer who received radiotherapy for lung cancer from 2010-2014, had a follow-up period of ≥ 3 months after radiotherapy, and did not have CPI at the time of radiotherapy. CPI was defined as pulmonary tuberculosis, non-tuberculous mycobacterial pulmonary disease, chronic pulmonary aspergillosis, or pulmonary actinomycosis. The cumulative incidence of CPI and overall survival (OS) were estimated using the Kaplan-Meier method, and a multivariable Cox proportional hazards analysis was performed to identify risk factors associated with CPI development.
Results
The median follow-up period was 2.3 years with OS rates of 55.6% and 37.6% at 2 and 5 years, respectively. CPI developed in 59 patients at a median of 1.8 years after radiotherapy, with cumulative incidence rates of 1.1%, 3.4%, 5.0%, and 6.8% at 1, 3, 5, and 7 years, respectively. A lower body mass index, interstitial lung disease, prior pulmonary tuberculosis, larger clinical target volume, history of lung cancer surgery or radiation pneumonitis, and use of inhaled corticosteroids were independent risk factors for CPI development.
Conclusion
The long-term survival rate of lung cancer patients receiving radiotherapy was not low, but the cumulative incidence of CPI gradually increased to 6.8% at 7 years after radiotherapy. Therefore, close monitoring of CPI development is required in surviving patients with risk factors.

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Invasive aspergillosis complicated in a patient with non-small cell lung cancer harboring RET fusion during treatment with RET-TKIs: a case report and literature review
Kaidiriye Setiwalidi, Yimeng Li, Yuyan Ma, Zhanpeng Hao, Yujia Zhao, Yuxin Zhang, Xuan Liang, Tao Tian, Zhiping Ruan, Yu Yao, Xiao Fu
Frontiers in Oncology.2024;[Epub] CrossRef

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Top Ten Lessons Learned from Trials in Oligometastatic Cancers: Vivian S. Tan, David A. Palma; Cancer Res Treat. 2023;55(1):5-14. Published online December 16, 2022; DOI: https://doi.org/10.4143/crt.2022.1460

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Recent evidence supports the role of aggressive local treatment in the oligometastatic setting. In this review, we discuss the top 10 lessons we have learned from trials in oligometastatic cancers. Major lessons learned pertain to definitions of oligometastatic disease, outcomes, toxicity, costs, and the combination of ablative therapies with systemic therapy, including immunotherapy. Barriers to accrual for trials and upcoming phase III trials are also reviewed. These lessons may help to inform clinical practice and may be the basis for future research in the oligometastatic space.

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In situ generated CdTe quantum dot-encapsulated hafnium polymer membrane to boost electrochemiluminescence analysis of tumor biomarkers
Haiyin Li, Zhixin Wang, Feng Li, Panpan Gai
Analytical and Bioanalytical Chemistry.2024; 416(21): 4769. CrossRef
Safety and Efficacy of Stereotactic Body Radiation Therapy for Ultra-central Thoracic Tumors: A Single Center Retrospective Review
George J. Li, Hendrick Tan, Humza Nusrat, Joe Chang, Hanbo Chen, Ian Poon, Jeevin Shahi, May Tsao, Yee Ung, Patrick Cheung, Alexander V. Louie
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Lung and Thoracic cancer

Optimal Definition of Oligometastasis Showing Survival Benefits of Local Therapies during Tyrosine Kinase Inhibitor Treatment: Yoon Jung Jang, Dong-gon Hyun, Wonjun Ji, Chang-Min Choi, Shinkyo Yoon, Dae Ho Lee, Sang-We Kim, Jae Cheol Lee; Cancer Res Treat. 2023;55(2):468-478. Published online November 28, 2022; DOI: https://doi.org/10.4143/crt.2022.1342

Abstract PDF Supplementary Material PubReader ePub: Purpose
We aimed to investigate the feasibility of four criteria on oligometastasis (OM) concerning clear survival benefits of local therapy (LT) during tyrosine kinase inhibitor (TKI) treatment in non–small cell lung cancer (NSCLC).
Materials and Methods
This single-center, retrospective study included patients with advanced NSCLC who received LT because of OM during TKI treatment at Asan Medical Center from January 2011 to December 2020. At the application of LT OM was classified according to four criteria: TNM, European Organization for Research and Treatment of Cancer Lung Cancer Group (EORTC-LCG), National Comprehensive Network (NCCN), and ORGAN. We compared survival outcomes between patients with and without OM.
Results
The median overall survival of the 117 patients included in the analysis was 70.8 months (95% confidence interval [CI], 56.6 to 85.1). The patients with OM meeting all four criteria (hazard ratio [HR] with 95% CI of TNM criteria 0.24 with 0.10-0.57; p=0.001, EORTC-LCG criteria 0.34 with 0.17-0.67; p=0.002, NCCN criteria 0.41 with 0.20-0.86; p=0.018 and ORGAN criteria 0.33 with 0.18-0.60; p < 0.001) had significantly longer survival compared with patients who did not after adjusting for confounding factors. Furthermore, increasing the number of extra-thoracic metastatic organs to two or more were independent predictive factors for worse survival outcomes (2 organs: HR, 3.51; 95% CI, 1.01 to 12.14; p=0.048; 3 organs: HR, 4.31; 95% CI, 0.94 to 19.73; p=0.060; 4 organs: HR, 24.47; 95% CI, 5.08 to 117.80; p < 0.001).
Conclusion
Patients with OM defined by all four criteria showed prognostic benefits from LT during TKI therapy.

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EGFR Mutation–Positive Unresectable Stage III Non-Squamous Lung Cancer Is Associated with a High Incidence of Brain Metastasis: Hongsik Kim, Sehhoon Park, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn; Cancer Res Treat. 2023;55(2):498-505. Published online October 4, 2022; DOI: https://doi.org/10.4143/crt.2022.388

Abstract PDF PubReader ePub

Purpose
The impact of epidermal growth factor receptor (EGFR) mutation in locally advanced non–small cell lung cancer (NSCLC) remains controversial. This study was conducted to investigate the clinical outcomes and recurrence patterns after definitive chemoradiotherapy (CRT) in patients with unresectable stage III non-squamous-cell lung cancer according to EGFR mutation status.
Materials and Methods
We retrospectively reviewed 604 patients with pathologically confirmed stage III NSCLC who were treated with definitive CRT and were examined for EGFR mutation at Samsung Medical Center, Korea, from January 2013 to December 2018. Among them, we identified 236 patients with stage III non-squamous-cell lung cancer who were treated with definitive CRT and were examined for EGFR mutation status. We analyzed the frequency of EGFR mutation, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and recurrence pattern.
Results
Among 236 patients, EGFR mutation was detected in 71 patients (30.1%) and the median follow-up duration was 41.7 months. There were no significant differences in PFS (9.9 vs. 10.9 months, p=0.236), and ORR to CRT (93.0% vs. 90.3%, p=0.623) according to EGFR mutation status. However, the EGFR mutant group showed significantly higher recurrence (88.7% vs. 75.2%, p=0.022), distant metastasis (76.1% vs. 61.2%, p=0.036) rates, especially brain (38.0% vs. 12.7%, p < 0.001), and better median OS (59.2 vs. 41.3 months, p=0.037) compared with patients without EGFR mutation.
Conclusion
Patients with EGFR mutation–positive unresectable stage III non-squamous lung cancer exhibited higher recurrence and distant metastasis rates, especially brain metastasis.

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Prognostic Factors in Postoperative Brain Metastases Derive From Non-small Cell Lung Cancer: A Retrospective Analysis
Haibin Chen, Liang Sun, Zhi Yang, Yuanyuan Qu, Nanyang Tong, Caixing Sun, Liang Xia
Clinical Medicine Insights: Oncology.2024;[Epub] CrossRef
Brain metastasis screening in the molecular age
Joanna K Tabor, Amanda Onoichenco, Vinayak Narayan, A Gabriella Wernicke, Randy S D’Amico, Morana Vojnic
Neuro-Oncology Advances.2023;[Epub] CrossRef

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General

Role of Local Treatment for Oligometastasis: A Comparability-Based Meta-Analysis: Chai Hong Rim, Won Kyung Cho, Jong Hoon Lee, Young Seok Kim, Yang-Gun Suh, Kyung Hwan Kim, Eui Kyu Chie, Yong Chan Ahn, The Oligometastasis Working Group, Korea Cancer Association; Cancer Res Treat. 2022;54(4):953-969. Published online August 16, 2022; DOI: https://doi.org/10.4143/crt.2022.329

Abstract PDF Supplementary Material PubReader ePub

Purpose
We intend to investigate the oncological efficacy and feasibility of local consolidative therapy (LCT) through a meta-analysis method.
Materials and Methods
Four databases including PubMed, MEDLINE, Embase, and Cochrane library were searched. Target studies are controlled trials comparing outcomes of LCT versus a control group. Primary endpoints are overall survival (OS) and progression-free survival (PFS).
Results
A total of 54 studies involving 7,242 patients were included. Pooled analyses showed that the LCT arm could achieve improved OS with pooled odds ratio of 2.896 (95% confidence interval [CI], 2.377 to 3.528; p < 0.001). Regarding PFS, pooled analyses showed pooled odds ratio of 3.045 (95% CI, 2.356 to 3.937; p < 0.001) in favor of the LCT arm. In the subgroup analyses including the studies with reliable comparability (e.g. randomized studies or intentionally matched studies without significant favorable prognosticator in LCT arms), pooled odds ratio was 2.548 (95% CI, 1.808 to 3.591; p < 0.001) favoring the LCT arm regarding OS. Regarding PFS, pooled OR was 2.656 (95% CI, 1.713 to 4.120; p < 0.001) which also favored the LCT arm. Subgroup analyses limited to the randomized controlled trials (RCT) were also performed and pooled odds ratios on OS and PFS were 1.535 (95% CI, 1.082 to 2.177; p=0.016) and 1.668 (95% CI, 1.187 to 2.344; p=0.003). The rates of grade ≥ 3 complications related to LCT was mostly low (< 10%) and not significantly higher compared to the control arm.
Conclusion
Pooled analyses results of all included studies, selected studies with reliable comparability, and RCT’s demonstrated the survival benefit of LCT. These consistent results suggest that LCT was beneficial to the patients with oligometastasis.

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