Cancer Research and Treatment

Phase II Efficacy and Safety of Pembrolizumab with Platinum Based Chemotherapy in Non-Small Cell Lung Cancer Patients with Untreated, Asymptomatic Brain Metastasis (PHOEBS): Junkyu Kim, Miran Han, Jinyong Kim, Sehhoon Park, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Sun Hye Shin, Kyungjong Lee, Sang-Won Um, Myung-Ju Ahn; Received October 10, 2025 Accepted March 18, 2026 Published online March 19, 2026; DOI: https://doi.org/10.4143/crt.2025.1100 [Accepted]

Abstract PDF: Purpose
Brain metastases are a serious complication in non-small cell lung cancer (NSCLC). However, data regarding efficacy of immune checkpoint inhibitors and chemotherapy combinations are limited. This phase II study aimed to evaluate the intracranial efficacy and safety of pembrolizumab and chemotherapy in treatment-naïve NSCLC patients with asymptomatic brain metastases.
Materials and Methods
This single-arm, phase II trial was conducted at Samsung Medical Center, Korea. Eligible patients had stage IV NSCLC with asymptomatic, untreated brain metastases and no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) alterations. Patients received pembrolizumab with chemotherapy every 3 weeks for 4 cycles, followed by pembrolizumab with or without maintenance chemotherapy up to 35 cycles. The primary endpoint was intracranial objective response rate (icORR). Secondary endpoints included intracranial progression free survival (icPFS), intracranial duration of response (icDoR), objective response rate (ORR), progression free survival (PFS), overall survival, and safety.
Results
Between February 2021 and June 2024, a total of 13 patients were enrolled. Due to challenges in recruiting patients, enrollment was discontinued after the 13 patients. The icORR was 46.2% (95% CI, 19.2–74.8), with 6 patients achieving partial response. The median icPFS was 9.8 months (95% CI, 5.2–21.5), and median icDoR was 9.3 months (95% CI, 4.0–20.3). Median PFS and overall survival was 7.2 months (95% CI, 2.4–12.3) and 10.7 months (95% CI, 7.2–21.5), respectively. Most treatment-related adverse events were grade 1–2.”
Conclusion
Pembrolizumab combined with chemotherapy demonstrated encouraging intracranial activity and manageable safety profile in NSCLC patients with untreated, asymptomatic brain metastases.

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Comparative Clinical and Economic Analysis of Robotic versus Video-assisted thoracoscopic Anatomical Resection for Lung Cancer: Ji Hyeon Park, Young Eun Hong, Hana Shim, Taeyoung Yun, Bubse Na, Kwon Joong Na, Hyun Joo Lee, In Kyu Park, Young Tae Kim, Chang Hyun Kang; Received February 27, 2025 Accepted March 16, 2026 Published online March 18, 2026; DOI: https://doi.org/10.4143/crt.2025.230 [Accepted]

Abstract PDF: Purpose
This study aimed to compare the clinical outcomes and costs of robotic-assisted thoracic surgery (RATS) and video-assisted thoracic surgery (VATS) in patients undergoing minimally invasive anatomical resection for primary lung cancer.
Materials and Methods
A retrospective analysis was conducted on 2,086 patients who underwent surgery at a single institution from January 2017 to July 2020, including 134 RATS and 1,952 VATS cases. Propensity score matching (PSM) was applied, resulting in 268 matched patients (134 RATS and 134 VATS). Cost data were obtained from hospital billing files, encompassing 20 categories, including total hospitalization fees, anesthesia fees, surgery fees, costs of surgical instruments and materials, and general examination fees.
Results
After PSM, RATS patients had a shorter median postoperative stay (5 days vs. 6 days, p = 0.009) and lower thoracotomy conversion rate (1.5% vs. 14.9%, p < 0.001) than VATS. However, RATS incurred higher total costs by an average of $1,230 (p < 0.001), mainly due to increased surgical expenses ($1,163, p < 0.001). In multivariate analysis, RATS (12.41%, p < 0.001), neoadjuvant therapy (13.3%, p = 0.005), complications (4.2%, p < 0.001), and length of stay (2.0%, p < 0.001) were found to be associated with higher costs.
Conclusion
Although RATS has been shown to reduce the thoracotomy conversion rate and length of hospital stay, it incurs higher costs than VATS, primarily due to increased surgical expenses. The justification for RATS should be further evaluated through sustainability and cost-effectiveness studies with long-term follow-up.

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Safety and Efficacy of Combining Metastasis-Directed Stereotactic Ablative Radiation Therapy with Tyrosine Kinase Inhibitors Versus Immune Checkpoint Inhibitors in Metastatic Hepatocellular Carcinoma: Eunyeong Yang, Jeong Il Yu, Hee Chul Park, Myung Ji Goh, Byeong Geun Song, Wonseok Kang, Dong Hyun Sinn, Geum-Youn Gwak, Yong-Han Paik, Joon Hyeok Lee, Moon Seok Choi, Jung Yong Hong, Minsuk Kwon, Nalee Kim; Received September 5, 2025 Accepted February 1, 2026 Published online February 3, 2026; DOI: https://doi.org/10.4143/crt.2025.966 [Accepted]

Abstract PDF: Purpose
Immune checkpoint inhibitors (ICIs) have become a standard therapy for metastatic hepatocellular carcinoma (HCC), often as an alternative to tyrosine kinase inhibitors (TKIs). However, safety data combining ICIs with stereotactic ablative radiotherapy (SABR) remain limited. We compared the safety and efficacy of SABR combined with ICIs versus TKIs in patients with extrahepatic metastatic HCC.
Materials and methods
This single-center retrospective study included patients with HCC who received SABR for extrahepatic metastases combined with either TKIs or ICIs within 30 days of SABR between January 2010 and June 2024. Adverse events (AEs; CTCAE v5.0) and oncologic outcomes were evaluated using logistic regression and Cox models.
Results
Among 103 patients with 128 SABR-treated lesions, 72 patients (90 lesions) received SABR+TKI and 31 patients (38 lesions) received SABR+ICI. Acute AEs occurred only in the SABR+TKI group (8.9%), predominantly grade 1. Grade 3 late AEs were rare, occurring in one case in each group, while late AEs of lower grades were more frequent with SABR+ICI (any-grade: 57.9% vs. 25.6%, p<0.001; grade ≥2: 23.7% vs. 8.9%, p=0.024). Multivariable analysis showed borderline increased risk of grade ≥2 late AEs with SABR+ICI (p=0.052). One-year local control, progression-free survival, and overall survival were 76.6%, 35.3%, and 72.3% respectively, with no significant differences between groups.
Conclusion
Metastasis-directed SABR combined with either TKIs or ICIs was generally well tolerated in patients with extrahepatic metastatic HCC, with rare grade 3 late AEs; grade ≥2 late AEs were more frequent with SABR plus ICIs, warranting prospective evaluation.

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Zolbetuximab Plus Chemotherapy as First-Line Treatment in Patients with Claudin 18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma: Korean Population Subgroup—Combined Efficacy and Safety Analysis from SPOTLIGHT and GLOW: Keun-Wook Lee, Sang Cheul Oh, Jong Gwang Kim, Sun Jin Sym, Byoung Yong Shim, Seok Yun Kang, In-Ho Kim, Jwa Hoon Kim, Hong Jae Chon, Sang-Hee Cho, Eun-Kee Song, Do-Youn Oh, Jin-Soo Kim, Young Iee Park, Won Ki Kang, Hyung-Don Kim, Janise Lee, Miri Yi, Min-Hee Ryu; Received August 28, 2025 Accepted December 4, 2025 Published online December 5, 2025; DOI: https://doi.org/10.4143/crt.2025.935 [Accepted]

Abstract PDF: Purpose
The phase 3 SPOTLIGHT and GLOW trials, in patients with claudin 18 isoform 2–positive, human epidermal growth factor receptor 2–negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma, demonstrated statistically significant and clinically meaningful improvement in progression-free survival (PFS) and overall survival (OS) with first-line zolbetuximab plus chemotherapy versus placebo plus chemotherapy. This analysis evaluated efficacy and safety in the Korean subgroup from SPOTLIGHT and GLOW.
Materials and Methods
Patients were randomized 1:1 to receive zolbetuximab plus chemotherapy or placebo plus chemotherapy (mFOLFOX6 [modified folinic acid, 5-fluorouracil, and oxaliplatin] or CAPOX [capecitabine and oxaliplatin]). Primary endpoint was PFS, assessed per RECIST v1.1 by independent review committee. Other efficacy and safety parameters were assessed.
Results
The Korean subgroup consisted of 49 patients in the zolbetuximab group and 47 in the placebo group. Median PFS (95% confidence interval [CI]) was 12.3 months (7.3-15.3), and median OS was 30.5 months (16.1-45.5) with zolbetuximab versus 8.1 months (4.2-10.4) and 15.8 months (11.8-19.7) with placebo, respectively. Most common TEAEs in patients who received zolbetuximab versus placebo were nausea (79.6% vs. 53.2%), vomiting (55.1% vs. 21.3%), and decreased appetite (53.1% vs. 23.4%). Treatment-related TEAEs led to discontinuation of zolbetuximab and placebo in 4.1% and 2.1% of patients, respectively.
Conclusion
Zolbetuximab plus chemotherapy demonstrated favorable PFS and OS versus placebo plus chemotherapy in the Korean subgroup, with numerically greater efficacy compared with the overall pooled population. This may be potentially attributable to low rates of zolbetuximab discontinuation and toxicity management.

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Trajectory of Lymph Node Metastasis Reflects the Molecular Features of Esophageal Squamous Cell Carcinoma: Jiho Park, Seong Yong Park, Ha Eun Kim, Se-Young Jo, JeongSoo Won, Dae Joon Kim, Sangwoo Kim; Received March 5, 2025 Accepted October 14, 2025 Published online October 15, 2025; DOI: https://doi.org/10.4143/crt.2025.257 [Accepted]

Abstract PDF: Purpose
Esophageal squamous cell carcinoma (ESCC) is frequently accompanied by lymph node metastasis (LNM) to the neck, chest, and abdomen. Despite its significance as a key prognostic factor, the genomic trajectory of LNM remains poorly understood. This study aimed to characterize the underlying patterns and genomic characteristics of LNM.
Materials and Methods
Whole-exome sequencing and transcriptome sequencing were performed on 45 multiregional samples (10 primary tumors, 10 normal esophageal tissues, and 25 lymph node tumors) from 10 ESCC patients who underwent esophagectomy with three-field lymphadenectomy. The temporal trajectory of metastasis was reconstructed through phylogenetic analysis, leveraging somatic mutations identified in the primary tumor and lymph nodes.
Results
Somatic mutations preceding metastasis included major driver mutations, such as TP53 and KMT2D, and displayed a mutational process associated with alcohol consumption (SBS16), emphasizing its influence on early tumorigenesis. In contrast, post-lymph node metastatic mutations were sporadic. Lymph nodes seeded later acquired mutations at a faster rate, suggesting increased genomic instability. In three of nine patients (33%), nodal skip metastasis (NSM) was observed, including two cases detected exclusively via genomic analysis, highlighting the necessity of phylogenetic assessment to avoid misclassification. Transcriptome analysis revealed activation of epithelial-mesenchymal transition and KRAS signaling pathways in NSM tumors, indicative of poor prognostic outcomes.
Conclusion
Our study provides a molecular understanding of LNM, emphasizes the potential importance of node-skipping patterns in ESCC, and underscores the utility of genomic analysis in elucidating the connection between LNM.

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Real World Efficacy of 1st-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 [Accepted]

Abstract PDF: 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 four 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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Extracellular Vesicle-Derived Adenosine as a Diagnostic Metabolic Biomarker for Pancreatic Ductal Adenocarcinoma: Tao Xia, Wenhui Ouyang, Jie Wang, Jinjing Wang, Yiping Mou, Zhengquan Yang, Hezhi Fang, Shanying Gui; Received May 12, 2025 Accepted September 11, 2025 Published online September 24, 2025; DOI: https://doi.org/10.4143/crt.2025.510 [Accepted]

Abstract PDF: Purpose
Current non-invasive diagnostic tools for pancreatic ductal adenocarcinoma (PDAC) exhibit limited sensitivity and specificity. This study aimed to identify more accurate plasma biomarkers by profiling extracellular vesicles (EVs), which are enriched in tumor-derived metabolites and proteins.
Materials and Methods
Plasma samples were collected under strict fasting and standardized processing protocols from patients diagnosed with PDAC, chronic pancreatitis (CP), and tumor-free controls (Ctrl). EVs were isolated from these plasma samples and subjected to comprehensive metabolomic and proteomic profiling to identify disease-specific biomarkers.
Results
A biomarker panel comprising adenosine, adenine, and N-acetylneuraminate (AAN) demonstrated outstanding diagnostic performance, achieving an area under the receiver operating characteristic curve (AUC) of 0.968 (95% CI: 0.92–1.00). At a fixed specificity of 96.8%, the panel yielded a sensitivity of 95.0% (95% CI: 85.0%–100.0%), significantly reducing the classification error from 30% with CA19-9 to 5% with the AAN panel. Among individual markers, adenosine alone showed high diagnostic power (AUC=0.952), correlating with increased expression of 5′-nucleotidase ecto (NT5E), indicative of elevated extracellular purine metabolism. Importantly, these features were unique to the EV compartment and outperformed markers derived from total plasma metabolite profiles.
Conclusion
The integration of EV metabolomics and proteomics revealed enhanced purine metabolism, particularly elevated extracellular adenosine, as a distinctive hallmark of PDAC. EV-derived adenosine emerges as a highly promising non-invasive biomarker with superior diagnostic accuracy compared to CA19-9.

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Concept of Depth of Invasion Can Improve Staging Performance in Patients with Resected Distal Cholangiocarcinoma: Validation of the American Joint Committee on Cancer Staging System: Won-Gun Yun, Yoon Soo Chae, Youngmin Han, Young Jae Cho, Hye-Sol Jung, Wooil Kwon, Joon Seong Park, Haeryoung Kim, Kyoung Bun Lee, Jin-Young Jang; Received April 12, 2025 Accepted August 22, 2025 Published online August 25, 2025; DOI: https://doi.org/10.4143/crt.2025.406 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
The American Joint Committee on Cancer (AJCC) staging system for distal cholangiocarcinoma (dCC) has evolved significantly. However, the prognostic correlation of the newly proposed staging system remains unclear. Therefore, we aimed to compare the staging performance between AJCC 7th and 8th editions for dCC.
Materials and Methods
We reviewed pathological slides of consecutive patients who underwent resection for dCC between 2000 and 2022. According to the AJCC 8th edition, depth of invasion was defined as the distance from the basement membrane of adjacent normal or dysplastic epithelium to the deepest tumor invasion. We analyzed changes in the T category from the AJCC 7th to 8th edition and assessed overall survival and recurrence based on these staging systems.
Results
Among 428 patients, application of the 8th edition resulted in down-staging of 272 (63.6%) patients and up-staging of only 13 (3.0%). Lymph node metastases were identified in 150 (35.1%) patients, with 29 (6.8%) having ≥ 4 metastatic nodes. The C-indices for overall survival and recurrence are 0.557 and 0.569 for the T category of the AJCC 7th edition, and 0.606 and 0.631 for that of the AJCC 8th edition (95% confidence interval for delta, 0.005 to 0.092 for survival, 0.023 to 0.100 for recurrence). Additionally, the T category of the 8th edition correlated more strongly with lymph node metastases than that of the 7th edition.
Conclusion
In dCC, the T category of the AJCC 8th edition demonstrates improved prognostic correlation and better alignment with lymph node metastases compared to that of the 7th edition.

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Preferential Sensitivity of the EGFR L858M/L861R Mutation to Second-Generation EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer: Chaelin Lee, Sheehyun Kim, Soyeon Kim, Taekeun Park, Miso Kim, Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Jeonghwan Youk; Received March 11, 2025 Accepted August 19, 2025 Published online August 20, 2025; DOI: https://doi.org/10.4143/crt.2025.279 [Epub ahead of print]

Abstract PDF Supplementary Material

Purpose
Non–small cell lung cancer (NSCLC) frequently harbors targetable epidermal growth factor receptor (EGFR) mutations. However, rare variants such as EGFR L858M or L861R remain poorly characterized. This study aimed to elucidate the oncogenic potential and EGFR tyrosine kinase inhibitors (TKIs) sensitivity of the EGFR L858M/L861R mutation to inform personalized treatment strategies.
Materials and Methods
Tumor samples from an NSCLC patient were analyzed using targeted panel sequencing and confirmed with the FoundationOne Liquid CDx assay. EGFR-mutant constructs, including L858M, L858R, L861R, L861Q, L858M/L861R, and L858R/L861Q, were generated and transduced into various cell lines. Cell viability, immunoblot, and soft agar colony formation assays were conducted to assess the oncogenicity and drug sensitivity, while computational protein modeling and docking simulations evaluated the drug-binding affinities of EGFR-TKIs.
Results
Ba/F3 cells expressing the EGFR L858M/L861R mutation exhibited robust interleukin-3–independent proliferation accompanied by markedly increased EGFR phosphorylation, while NIH-3T3 cells showed anchorage-independent colony formation. Compared to other mutations, cells expressing EGFR L858M/L861R mutation were less sensitive to first-generation EGFR-TKIs (gefitinib, erlotinib) and third-generation EGFR-TKIs (osimertinib, lazertinib), whereas second-generation EGFR-TKIs (afatinib, poziotinib) demonstrated potent inhibitory effects. Computational modeling revealed a narrower drug-binding efficiency of first-generation inhibitors.
Conclusion
The EGFR L858M/L861R mutation drives strong oncogenic signaling and exhibits preferential sensitivity to second-generation EGFR-TKIs. These findings underscore the importance of accurate molecular diagnosis for guiding effective, personalized therapeutic strategies in NSCLC.

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Real-World Outcomes and Subsequent Treatment Patterns in Patients with Advanced Non-Small Cell Lung Cancer and Atypical EGFR Mutations Receiving First-Line Osimertinib Monotherapy
Jorge J. Nieva, Xuejun Wang, Deborah Doroshow, Leslie Servidio, Miranda Cooper, Yan Kwan Lau, Pritesh S. Karia, Jacqulyne Robichaux
Oncology and Therapy.2026; 14(1): 225. CrossRef

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Efficacy and Safety of Lenvatinib Plus Everolimus in Metastatic Renal Cell Carcinoma after Immune Checkpoint and VEGFR Tyrosine Kinase Inhibitors Treatment: So Heun Lee, Inkeun Park, Shinkyo Yoon, Jae Lyun Lee; Received June 17, 2025 Accepted August 12, 2025 Published online August 13, 2025; DOI: https://doi.org/10.4143/crt.2025.628 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub

Purpose
Real-world data on the efficacy and safety of lenvatinib plus everolimus in metastatic renal cell carcinoma (RCC) after failure of immune checkpoint inhibitors (ICIs) and/or vascular endothelial growth factor receptor (VEGFR)–targeted tyrosine kinase inhibitors (TKIs) remain limited.
Materials and Methods
This single-center retrospective study included patients with metastatic RCC treated with lenvatinib plus everolimus as second-line or later therapy at Asan Medical Center, Korea, between September 2017 and June 2024. Data on dose adjustments, treatment response, survival, and adverse events were collected from electronic medical records. Primary endpoints were objective response rate (ORR) and progression-free survival (PFS); secondary endpoints included overall survival (OS), time to progression, adverse events, and prognostic factors.
Results
A total of 83 patients were included, predominantly with clear cell histology (90.4%). The median number of prior therapies was four (range, 1 to 7), with 80.7% receiving the combination as fourth-line or beyond. All had prior anti-angiogenic TKI exposure, 86.7% had received ICIs, and 37.3% had prior mTOR inhibitor therapy. The ORR was 40.0%, with disease control at 81.3%. Median PFS and OS were 5.4 months (95% confidence intervals [CI], 4.4 to 6.8) and 8.5 months (95% CI, 6.3 to 12.1), respectively. Efficacy was consistent across key subgroups. During the treatment, lenvatinib dose reductions were required in 55.4% of patients, and 26.5% experienced treatment interruptions. Grade ≥ 3 proteinuria occurred in 22.9%.
Conclusion
Lenvatinib plus everolimus demonstrated promising efficacy in heavily pretreated patients with metastatic RCC, including those previously exposed to VEGFR-targeted TKIs and/or ICIs. Further studies are warranted to optimize treatment strategies in this patient population.

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Diosmetin alleviates the immunosuppressive tumor microenvironment in esophageal squamous cell carcinoma by dually inhibiting angiogenesis and promoting CD8+T cell cytotoxicity
Xiaoxuan Duan, Xiaoshuo Dai, Xiaoya Li, Yingfei Wang, Kai Zhang, Wei Chen, Yihuan Chen, Jimin Zhao, Yan Qiao, Xiang Li, Saijun Mo, Fang Tian, Ziming Dong, Kangdong Liu, Jing Lu
Phytomedicine.2026; : 158036. CrossRef

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Risk Stratification in T4 or N3 Nasopharyngeal Carcinoma: Lin-Feng Guo, Lu-Chao Zhu, Yi-Feng Yu, Zhen-Zhen Lu, Qin Lin, San-Gang Wu; Received May 28, 2025 Accepted August 11, 2025 Published online August 12, 2025; DOI: https://doi.org/10.4143/crt.2025.573 [Epub ahead of print]

Abstract PDF PubReader ePub: Purpose
This study aimed to investigate the prognostic heterogeneity among stage III nasopharyngeal carcinoma (NPC) patients according to the 9th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging system to identify potential subgroups requiring tailored therapeutic strategies.
Materials and Methods
We retrospectively included stage III patients (T1-3N3 or T4N0-3) who were diagnosed with NPC between January 2015 and December 2021 according to the 9th edition of the AJCC/UICC staging system. Kaplan-Meier method and multivariable Cox regression analyses were used for statistical analysis.
Results
A total of 309 patients were included in this study. A total of 92/309 (29.8%) patients developed locoregional recurrence and/or distant metastasis with a median follow-up of 52.9 months. Those with T4N3 disease had significantly lower distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) but comparable locoregional relapse-free survival (LRFS) to those with T1-3N3 and T4N0-2 disease. Those with T4N3 disease had comparable LRFS but significantly lower 5-year DMFS (78.7% vs. 44.7%, p < 0.001), PFS (65.7% vs. 27.6%, p < 0.001), and OS (77.1% vs. 45.9%, p < 0.001) compared to those with stage T4N0-2 and T1-3N3 diseases. Similar results were confirmed using the multivariate analysis.
Conclusion
Our study demonstrates the prognostic heterogeneity of stage III disease within the 9th edition NPC staging system. T4N3 category should be considered separately and treated as a distinct entity regardless of the staging editions.

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Effectiveness of Radiotherapy for Hepatocellular Carcinoma with Lymph Node Metastasis: A Meta-Analysis: Sooyoung Hwang, Seoon Hur, Won Sup Yoon, Sunmin Park, Chai Hong Rim; Received May 2, 2025 Accepted August 11, 2025 Published online August 12, 2025; DOI: https://doi.org/10.4143/crt.2025.475 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
Lymph node metastasis (LNM) of hepatocellular carcinoma (HCC) carries a poor prognosis; however, no standard treatment has been established. Radiotherapy (RT) has demonstrated favorable tumor response, with the advantage of being less affected by anatomical hindrances.
Materials and Methods
Databases were searched up to April 2024. The inclusion criteria were ≥ 5 patients with HCC LNM, studies that performed external RT, and reporting survival or response rate (RR). The main effect measures are pooled 1- and 2-year overall survival (OS) rates, RR, and grade ≥ 3 complications.
Results
Twelve studies involving 825 patients were included. The pooled 1-year OS rate and 2-year OS rate were 49.3% (95% confidence interval [CI], 39.2 to 59.4) and 24.5% (95% CI, 17.0 to 34.0), respectively. The median OS ranged from 5.8 to 29.7 months, with a median value of 9.7 months. In one study, 14.7% of patients were prescribed an immunoagent. In other studies, some patients received sorafenib, but no specific systemic therapy was performed for the majority. The pooled RR was 75.1% (95% CI, 66.9 to 81.8). The pooled RR of high dose and low dose groups was 83.8% (95% CI, 76.3 to 89.3) vs. 55.6% (95% CI, 44.4 to 66.3), respectively (p < 0.001). The pooled rate of grade ≥ 3 gastrointestinal toxicity was 3.7% (95% CI, 2.1 to 6.6).
Conclusion
RT is an effective and feasible palliative option for HCC LNM. Further research of combined treatment with novel systemic agents are necessary.

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Genitourinary cancer

Adjuvant Pembrolizumab Versus Placebo for Renal Cell Carcinoma in the East Asian Subgroup of the Phase 3 KEYNOTE-564 Study: Se Hoon Park, Yen-Hwa Chang, Jae Lyun Lee, Toni K. Choueiri, Go Kimura, Jinsoo Chung, Naoya Masumori, Kazuo Nishimura, Minoru Kato, Haruaki Kato, Kazuyuki Numakura, Chao-Hsiang Chang, Satoshi Anai, Hiroyuki Tsunemori, Chung-Hsin Chen, Jianxin Lin, Aymen Elfiky, Joseph E. Burgents, Hiroshi Kitamura; Cancer Res Treat. 2026;58(2):613-621. Published online June 26, 2025; DOI: https://doi.org/10.4143/crt.2025.365

Abstract PDF Supplementary Material PubReader ePub

Purpose
Adjuvant pembrolizumab improved disease-free survival (DFS) and overall survival (OS) versus placebo in participants with renal cell carcinoma (RCC) at increased risk of recurrence after nephrectomy in the global phase 3 KEYNOTE-564 study. This post hoc subgroup analysis evaluated the efficacy and safety of adjuvant pembrolizumab in East Asian (Japan, South Korea, and Taiwan) participants enrolled in KEYNOTE-564.
Materials and Methods
Eligible participants were randomly assigned 1:1 to receive adjuvant pembrolizumab 200 mg or placebo intravenously every 3 weeks for ≤ 17 cycles. The primary endpoint was DFS by investigator assessment. OS was a key secondary endpoint. Safety was a secondary endpoint.
Results
The East Asian subgroup included 126 participants (pembrolizumab, n=58; placebo, n=68). Median follow-up was 62.1 months (range, 49.6 to 73.0 months). Hazard ratio for DFS with pembrolizumab versus placebo was 0.70 (95% confidence interval 0.41 to 1.20). Median DFS was not reached with pembrolizumab versus 58.8 months with placebo; estimated 48-month rate was 61.3% versus 51.2%. Hazard ratio for OS was 0.47 (95% confidence interval, 0.15 to 1.49). Median OS was not reached with pembrolizumab and placebo; estimated 48-month rate was 94.8% versus 91.2%. Treatment-related adverse events occurred in 70.7% of participants (29.3% grade 3 or 4) receiving pembrolizumab and 36.8% of participants (0.0% grade 3 or 4) receiving placebo. No pembrolizumab-related deaths occurred.
Conclusion
In the KEYNOTE-564 East Asian subgroup, adjuvant pembrolizumab provided DFS and OS benefits versus placebo and had a safety profile consistent with the global results. These results further support pembrolizumab as adjuvant treatment for East Asian patients with RCC at increased risk of recurrence after nephrectomy.

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Reply to Editorial Comment: Racial Disparities in Patient Survival and Clinical Features of Recurrence After Surgery for Nonmetastatic Renal Cell Carcinoma: An International Multicenter Study
Masaki Kobayashi, Hajime Tanaka, Yasuhisa Fujii
JU Open Plus.2025;[Epub] CrossRef

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Head and Neck cancer

NOVA1 Activation Modulates the Tumor Immune Microenvironment through STING Phosphorylation in Head and Neck Squamous Cell Carcinoma: Sehui Kim, Hyang Mi Kim, Jae Min Bae, Sun Och Yoon; Cancer Res Treat. 2026;58(2):423-433. Published online June 18, 2025; DOI: https://doi.org/10.4143/crt.2025.333

Abstract PDF Supplementary Material PubReader ePub: Purpose
Neuro-oncological ventral antigen 1 (NOVA1), a neuron-specific pre-mRNA splicing factor, is involved in neuronal development and oncogenesis. NOVA1 overexpression is associated with favorable prognosis in head and neck squamous cell carcinoma (HNSCC) and gastric adenocarcinoma, whereas its downregulation correlates with poor outcomes. High NOVA1 levels in these cancers correlate with increased CD3⁺ and CD8⁺ T lymphocyte densities, suggesting involvement in tumor immune-inflammatory signals. This study explores NOVA1's role in regulating the immune-inflammatory cGAS-STING pathway in HNSCC cells and clinical tissues.
Materials and Methods
HNSCC cell lines (FaDu, YD-10B, SNU-1066, and SNU-1076) were transfected with NOVA1 and poly(dA:dT). Quantitative real-time polymerase chain reaction and Western blot analysis were used to assess gene/protein expression. Enzymelinked immunosorbent assay quantified cytokine levels, and immunoprecipitation assessed protein interactions. Clinical tissue samples from 234 HNSCC patients were analyzed using immunohistochemistry to correlate NOVA1 and STING pathway markers with immune cell infiltration.
Results
NOVA1 overexpression in HNSCC cells increased phosphorylation of STING (p-STING) without altering cGAS or TBK1. Immunoprecipitation showed an interaction between NOVA1 and p-STING. Overexpression of NOVA1, particularly with poly(dA:dT) treatment, tended to elevate CCL5 and CXCL10 expression. In clinical samples, NOVA1 expression strongly correlated with p-STING levels (r=0.749, p<0.001). Higher NOVA1 and p-STING expressions were linked to increased infiltration of CD3⁺ T cells, CD8⁺ T cells, and FOXP3⁺ regulatory T cells.
Conclusion
NOVA1 modulates the cGAS-STING pathway through STING phosphorylation and associated immune responses in HNSCC, providing a potential therapeutic target for enhancing anti-tumor immunity.

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Gastrointestinal cancer

Combined Transarterial Chemoembolization and External Beam Radiotherapy for Identifying Surgical Candidates for Hepatocellular Carcinoma with Macroscopic Vascular Invasion: A Propensity Score–Weighted Analysis: Sumin Lee, Jinhong Jung, Jonggi Choi, So Yeon Kim, Jin Hyoung Kim, Danbi Lee, Ju Hyun Shim, Kang Mo Kim, Young-Suk Lim, Han Chu Lee, Gi-Won Song, Jin-hong Park, Sang Min Yoon; Cancer Res Treat. 2026;58(1):275-283. Published online May 22, 2025; DOI: https://doi.org/10.4143/crt.2025.076

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to evaluate the role of hepatic resection in patients with objective responses after combined transarterial chemoembolization (TACE) and radiotherapy (RT) for hepatocellular carcinoma (HCC) with macroscopic vascular invasion (MVI).
Materials and Methods
We retrospectively reviewed the patients treated with combined TACE and RT for HCC with MVI between 2010 and 2015. Some of the patients with objective responses underwent hepatic resection or liver transplantation; to investigate the impact of surgery, patients with objective responses who did not undergo surgery were selected as the control group. Survival outcomes were compared using a propensity score–based stabilized inverse probability of treatment weighting method.
Results
Out of the 170 patients with objective responses after combined TACE and RT, 41 patients underwent surgery, including eight liver transplantations. The unweighted surgery group was younger and had a higher proportion of solitary tumors and unilateral vascular involvement. After adjustment, the 3-year overall survival (OS) rates were 61.0% and 28.6% in the surgery and non-surgery groups, respectively. The most important prognostic factor for OS was surgery (adjusted Cox hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.17 to 0.46; p < 0.001). Complete response after TACE and RT (vs. partial response) was also a significant prognostic factor for OS (adjusted HR, 0.41; 95% CI, 0.27 to 0.61; p < 0.001). There was no surgical mortality. Four patients (9.8%) required additional surgery due to bleeding or graft failure.
Conclusion
Hepatic resection was significantly associated with improved OS in patients who showed objective responses after receiving combined TACE and RT for HCC with MVI.

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Multimodal deep learning model for predicting prognosis following radiotherapy-based combination therapy in unresectable hepatocellular carcinoma
Haoming Xia, Qizhen Huang, Ziyue Huang, Ziqi Zhou, Yongyi Zeng, Jingguang Ma, Xiangyu Fan, Yechong Huang, Yuexi Dong, Haitao Zhao, Gong Li, Jitao Wang, Shizhong Yang, Jiahong Dong
Cancer Letters.2026; 636: 218122. CrossRef

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Pediatric cancer

Malignant Hepatocellular Neoplasm, Not Otherwise Specified, Displays Poorer Chemoresponsiveness and Postoperative Prognosis Than Hepatoblastoma: In Hye Song, Sujin Gang, Hee Mang Yoon, Pyeong Hwa Kim, Bokyung Ahn, Jihun Kim, Deok Hoon Kim, Jung-Man Namgoong, Kyung-Nam Koh; Cancer Res Treat. 2026;58(2):642-655. Published online May 12, 2025; DOI: https://doi.org/10.4143/crt.2025.117

Abstract PDF Supplementary Material PubReader ePub

Purpose
Malignant hepatocellular neoplasm, not otherwise specified (HCN-NOS) is a provisional diagnostic entity, characterised by intermediate or a combination of hepatoblastoma and pediatric hepatocellular carcinoma (p-HCC) features. We compared the characteristics of HCN-NOS with hepatoblastoma and p-HCC.
Materials and Methods
The records of 148 pediatric patients diagnosed with hepatocellular malignancy after resection were retrieved from the institutional database. Clinical parameters and histopathology slides were reviewed to re-establish each patient’s diagnosis. Molecular analyses were conducted in 37 patients.
Results
Patients were profiled as 21 (14.2%) with HCN-NOS, 109 (73.6%) with hepatoblastoma, and 18 (12.2%) with p-HCC. The median age was 8.6 years in HCN-NOS, 1.2 years in hepatoblastoma, and 7.9 years in p-HCC. Background liver disease was frequently observed in p-HCC (11/18, 61%) but infrequent in HCN-NOS (4/21, 19%) and hepatoblastoma (4/109, 3.7%). HCN-NOS presented with a more advanced PRETEXT stage (p=0.012), metastasis (p < 0.001), and lymphovascular invasion (p < 0.001) than hepatoblastoma and p-HCC. Patients with HCN-NOS received longer cycles of preoperative chemotherapy; however, they reported a lower decrease in serum alpha-fetoprotein and tumor size than hepatoblastoma (p=0.043, p=0.004, and p=0.044, respectively). HCN-NOS was an independent poor prognostic factor for event-free survival (hazard ratio, 4.968; 95% confidence interval, 2.004 to 12.32; p < 0.001).
Conclusion
The possibility of HCN-NOS should be considered in pediatric patients with liver cancer, especially those ≥ 5 years old with no background liver disease. Because HCN-NOS exhibits poor chemoresponsiveness and unfavourable postoperative prognosis, liver transplantation should be strongly considered.

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Conversion Hepatectomy After New FP Therapy for Malignant Hepatocellular Neoplasm, Not Otherwise Specified: A Case Report
Etsuko Moriyama, Hironori Koga, Takashi Niizeki, Hideki Iwamoto, Shigeo Shimose, Tomotake Shirono, Takahiko Tokushige, Masahito Nakano, Ryoko Kuromatsu, Toru Goto, Masaki Honda, Taizo Hibi, Yoshiki Mikami, Reiichiro Kondo, Jun Akiba, Takumi Kawaguchi
Hepatology Research.2026;[Epub] CrossRef

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Lung and Thoracic cancer

Clinical Relevance of Starting Alectinib at a Reduced Dose in Patients with ALK-Positive Non–Small Cell Lung Cancer: Junkyu Kim, Min-Ji Kim, Jinyong Kim, Sehhoon Park, Hyun Ae Jung, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Jong-Mu Sun; Cancer Res Treat. 2026;58(2):434-442. Published online April 24, 2025; DOI: https://doi.org/10.4143/crt.2024.1209

Abstract PDF Supplementary Material PubReader ePub: Purpose
Alectinib has been approved for anaplastic lymphoma kinase (ALK)–positive non–small cell lung cancer (NSCLC) at 300 mg twice daily in Japan, lower than global standard of 600 mg twice daily. This study evaluated the clinical relevance of the reduced dose by comparing outcomes between the two doses.
Materials and Methods
This study included patients with advanced ALK-positive NSCLC who received alectinib at Samsung Medical Center, Korea. The progression-free survival (PFS), overall survival, cumulative incidence of central nervous system (CNS) progression, and safety profiles were retrospectively reviewed and compared.
Results
Among 306 patients, 32 and 274 received alectinib at either 300 or 600 mg twice daily, respectively. The 300 mg group showed a slight but not significant advantage in PFS (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.44 to 1.51; p=0.51) and overall survival (HR, 0.51; 95% CI, 0.20 to 1.21; p=0.13). Superior outcome with 300 mg was remarkable in patients with lower body weight (≤ 60 kg), but diminished in patients with higher body weights. Patients with baseline brain metastasis in the 300 mg group exhibited a slight increase in incidence of CNS failure (HR, 1.76; 95% CI, 0.53 to 5.8; p=0.36). Although the safety profiles were mostly mild, adverse events were more frequent in the 600 mg group, 50% of which requiring dose reduction.
Conclusion
Alectinib at 300 mg twice daily seems an acceptable dose in East Asians with ALK-positive NSCLC. Notably, our data favor 300 mg twice daily in patients with lower body weight and no baseline brain metastasis, considering the more tolerable safety profiles and the potential to reduce medical costs.

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The Profile of Gut Microbiota in Carcinogenesis Driven by Mutant EGFR in Non–Small Cell Lung Cancer: Da-Som Kim, Eun Hye Kim, Ji Yong Kim, Dong Ha Kim, Yun Jung Choi, Jaeyi Jeong, Young Hoon Sung, Dong-Cheol Woo, Chong Jai Kim, Jae Cheol Lee, Miyong Yun, Jin-Yong Jeong, Jin Kyung Rho; Cancer Res Treat. 2026;58(1):115-127. Published online March 4, 2025; DOI: https://doi.org/10.4143/crt.2024.1177

Abstract PDF PubReader ePub

Purpose
Accumulating evidence has clarified that gut dysbiosis is involved in lung cancer development and progression. Although the relationship between tumors and gut microbiota has been extensively studied using clinical samples, no studies have examined the association between mutant epidermal growth factor receptor (EGFR)–induced lung carcinogenesis and dysbiosis in gut microbiota. Therefore, we investigated the gut microbiota profiles in stool samples from human lung-specific conditional EGFR-mutant transgenic mice during lung tumor carcinogenesis.
Materials and Methods
Stool samples were collected before tamoxifen treatment (V1) and at each time point following mutant EGFR expression in lung tissue (V2) and lung tumor appearance (V3). Fecal 16S rRNA taxonomy was analyzed to assess microbial diversity, composition, and dynamic changes at each time point.
Results
We found that microbiota richness and diversity were significantly elevated when tumors developed and grew in the lung. Phylogenetic analysis of the microbial community revealed that Lachnospiraceae, Ruminococcaceae, Porphyromonadaceae, Rhodospirillaceae, Odoribacteraceae, and Desulfovibrionaceae showed a significant increase at the V3 stage compared to the V1 stage at the family level. In contrast, Lactobacillaceae, Bacteroidaceae, Muribaculaceae, Coriobacteriaceae, and Rikenellaceae significantly decreased at the V3 stage compared to the V1 stage. Furthermore, Lactobacillus species, also known as short chain fatty acid-producing bacteria, were relatively abundant at the V1 stage but were depleted with the occurrence of lung tumors at the V3 stage.
Conclusion
Changes in gut microbiota, such as Lactobacillus species, may be a predictive factor for the emergence and progression of tumors in an animal model of lung adenocarcinoma induced by mutant EGFR.

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Microbiome and EGFR -mutant non-small cell lung cancer: a complex interplay
Serena Eccher, Marco Sposito, Ilaria Mariangela Scaglione, Luca Pasqualin, Michele Rota, Adele Bonato, Lucia Longo, Alice Avancini, Ilaria Trestini, Daniela Tregnago, Jessica Insolda, Michele Milella, Sara Pilotto, Lorenzo Belluomini
Expert Review of Clinical Immunology.2026; : 1. CrossRef
Gut microbiota and metabolites: emerging prospects in the treatment of non-small cell lung cancer
Jing-Mian Jiao, Chen-Guang Liu, Dan Zang, Jun Chen
Frontiers in Immunology.2025;[Epub] CrossRef
Study on the Impact of Changes in Intestinal Microbiota Structure of Lung Cancer Patients on the Efficacy of Immune Checkpoint Inhibitors
静鲁
Advances in Clinical Medicine.2025; 15(11): 744. CrossRef

3,125 View
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Gastrointestinal cancer

Evaluation of Nomenclature of Fatty Liver Disease in Association with Hepatocellular Carcinoma: A 14.5-Year Cohort Study in Korea: Tung Hoang, Jeonghee Lee, Bo Hyun Kim, Yuri Cho, Jeongseon Kim; Cancer Res Treat. 2025;57(4):1144-1155. Published online February 11, 2025; DOI: https://doi.org/10.4143/crt.2024.876

Abstract PDF Supplementary Material PubReader ePub

Purpose
New nomenclature has incorporated metabolic traits and/or alcohol intake history to replace nonalcoholic fatty liver disease (NAFLD). Concerning the performance of different terminologies in Asian population, this study aimed to investigate the risk of developing hepatocellular carcinoma (HCC) in persons meeting the criteria for subclasses of fatty liver disease.
Materials and Methods
Between 2002 and 2021, 28,749 participants from the cancer registry linkage, who had no prior history of HCC, were prospectively included. Fatty liver disease was defined using abdominal sonography and fatty liver index. Participants were classified as having NAFLD, metabolic dysfunction–associated fatty liver disease (MAFLD), metabolic dysfunction–associated steatotic liver disease (MASLD), steatotic liver disease with increased alcohol intake (MetALD), or alcohol-related liver disease (ALD) and their association with HCC risk was investigated using Cox regression models.
Results
During a median follow-up of 14.5 years, 143 HCC cases were newly diagnosed. The prevalences of NAFLD and MASLD were 19.7% and 18.7%, respectively, whereas MAFLD was observed in 32.3% of the study population. Given the low proportion of excessive alcohol consumption, we identified 3.3% MetALD and 3.5% ALD cases. Overall, MAFLD was suggestively associated with HCC risk (hazard ratio, 1.40; 95% confidence interval, 0.99 to 1.98). In contrast, the results for other nomenclature were not significant.
Conclusion
Our results suggest the importance of both fatty liver and the presence of metabolic dysfunction in relation to HCC risk and the need to reconsider alcohol intake thresholds in the diagnostic criteria for NAFLD and MASLD within the Korean population.

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Distinct Laboratory and Clinical Features of Metabolic and Alcohol-Related Liver Disease (MetALD): A Systematic Review and Meta-Analysis
Maria Tampaki, Vasileios Lekakis, Christos Chologkitas, Stergios Α. Polyzos, Evangelos Cholongitas
Current Obesity Reports.2026;[Epub] CrossRef
Dual etiology vs. MetALD: how MAFLD and MASLD address liver diseases coexistence
Shadi Zerehpooshnesfchi, Amedeo Lonardo, Jian-Gao Fan, Reda Elwakil, Tawesak Tanwandee, Munira Y. Altarrah, Necati Örmeci, Mohammed Eslam
Metabolism and Target Organ Damage.2025;[Epub] CrossRef
Comment on " posttreatment FIB-4 score change predicts hepatocellular carcinoma in chronic hepatitis C patients: Findings from the Taiwan hepatitis C registry program"
Junwei Guo, Dongsheng Huang
Journal of the Formosan Medical Association.2025;[Epub] CrossRef
MAFLD vs. MASLD: a year in review
Mingqian Jiang, Amna Subhan Butt, Ian Homer Cua, Ziyan Pan, Said A Al-Busafi, Nahum Méndez-Sánchez, Mohammed Eslam
Expert Review of Endocrinology & Metabolism.2025; 20(4): 267. CrossRef
Risk of hepatic and extrahepatic outcomes associated with metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction and alcohol-associated steatotic liver disease: a systematic review and meta-analysis
Ciro Celsa, Grazia Pennisi, Adele Tulone, Giacinta Ciancimino, Marco Vaccaro, Fabiana Pecorella, Gabriele Di Maria, Marco Enea, Federico Midiri, Alessandro Mantovani, Giovanni Targher, Aleksander Krag, Mary E Rinella, Calogero Cammà, Salvatore Petta
The Lancet Gastroenterology & Hepatology.2025; 10(11): 998. CrossRef

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Preoperative Prediction Model for Early Recurrence of Intrahepatic Cholangiocarcinoma after Surgical Resection: Development and External Validation Study: Dong Hwan Kim, Sang Hyun Choi, Sehee Kim, Hyungjin Rhee, Eun-Suk Cho, Suk-Keu Yeom, Sumi Park, Seung Soo Lee, Mi-Suk Park; Cancer Res Treat. 2025;57(4):1156-1166. Published online February 5, 2025; DOI: https://doi.org/10.4143/crt.2024.1187

Abstract PDF Supplementary Material PubReader ePub

Purpose
We aimed to develop a preoperative risk scoring system to predict early recurrence (ER) of intrahepatic cholangiocarcinoma (ICCA) after resection, utilizing clinical and computed tomography (CT) features.
Materials and Methods
This multicenter study included 365 patients who underwent curative-intent surgical resection for ICCA at six institutions between 2009 and 2016. Of these, 264 patients from one institution constituted the development cohort, while 101 patients from the other institutions constituted the external validation cohort. Logistic regression models were constructed to predict ER based on preoperative variables and were subsequently translated into a risk scoring system. The discrimination performance of the risk scoring system was validated using external data and compared to the American Joint Committee on Cancer (AJCC) TNM staging system.
Results
Among the 365 patients (mean age, 62±10 years), 153 had ER. A preoperative risk scoring system that incorporated both clinical and CT features demonstrated superior discriminatory performance compared to the postoperative AJCC TNM staging system in both the development (area under the curve [AUC], 0.78 vs. 0.68; p=0.002) and validation cohorts (AUC, 0.69 vs. 0.66; p=0.641). The preoperative risk scoring system effectively stratified patients based on their risk for ER: the 1-year recurrence-free survival rates for the low, intermediate, and high-risk groups were 85.5%, 56.6%, and 15.6%, respectively (p < 0.001) in the development cohort, and 87.5%, 58.5%, and 25.0%, respectively (p < 0.001) in the validation cohort.
Conclusion
A preoperative risk scoring system that incorporates clinical and CT imaging features was valuable in identifying high-risk patients with ICCA for ER following resection.

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Preoperative Prognostic Score for Patients with Intrahepatic Cholangiocarcinoma Undergoing Curative-Intent Resection
Jarin Chindaprasirt, Thanachai Sanlung, Piyakarn Watcharenwong, Vasin Thanasukarn, Apiwat Jareanrat, Natcha Khuntikeo, Tharatip Srisuk, Prakasit Sa-Ngiamwibool, Chaiwat Aphivatanasiri, Watcharin Loilome, Piya Prajumwongs, Attapol Titapun
Medical Sciences.2026; 14(1): 23. CrossRef

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1 Crossref

Head and Neck cancer

Differential Efficacy of Alpelisib by PIK3CA Mutation Site in Head and Neck Squamous Cell Carcinoma: An Analysis from the KCSG HN 15-16 TRIUMPH Trial: Kyoo Hyun Kim, Shinwon Hwang, Min Kyoung Kim, Keon-Uk Park, Tak Yun, Keun-Wook Lee, Joo Hang Kim, Bhumsuk Keam, Byoung Chul Cho, So Yeon Oh, Sang Hee Cho, Sangwoo Kim, Sung-Bae Kim, Min Hee Hong, Hye Ryun Kim; Cancer Res Treat. 2025;57(4):968-980. Published online January 31, 2025; DOI: https://doi.org/10.4143/crt.2024.1195

Abstract PDF Supplementary Material PubReader ePub

Purpose
The TRIUMPH trial was a biomarker-driven umbrella trial for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). This analysis focuses on the PIK3CAα (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) inhibitor alpelisib (arm 1) in patients with phosphoinositide 3-kinase (PI3K) pathway alterations.
Materials and Methods
Patients with PI3K pathway altered tumors were enrolled in the alpelisib arm of the TRIUMPH study. We conducted a detailed analysis of the correlation between PI3K pathway mutations and treatment outcomes including disease control rate, overall survival (OS), and progression-free survival (PFS).
Results
From October 2017 and August 2020, 203 were enrolled, with 42 treated with alpelisib. Response evaluation was possible for 33 patients. Genomic profiles revealed PIK3CA amplifications in 26.2%, and point mutations in E542K (26.2%), E545K (23.8%), and H1047R (9.5%). Neither PIK3CA amplification nor co-occurring TP53 mutations had a notable influence on alpelisib response or survival outcomes. Although the overall response rates were similar between helical domain mutations (E542, E545) and kinase domain mutation (H1047), patients with H1047 mutation exhibited significantly poorer PFS compared to those with non-H1047 PIK3CA alterations (1.6 vs. 7.3 months, p=0.017). OS in patients with H1047 kinase domain mutation showed a trend toward being shorter compared to others, though this difference did not reach statistical significance.
Conclusion
Alpelisib showed differential efficacy based on PI3K pathway alterations in patients with R/M HNSCC and was well-tolerated. These findings suggest the usefulness of next-generation sequencing testing-based decision-making when using the targeted agents in R/M HNSCC. We need to confirm results in larger cohorts.

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Actualités 2025 par le comité de rédaction du Bulletin du Cancer : congrès ASCO, ESMO et au-delà
Stéphane Vignot, Audrey Bellesoeur, Delphine Borchiellini, Carole Bouleuc, Romain Cohen, Alexandre de Nonneville, Frédéric Delom, Serge Evrard, Nelly Firmin, Virginie Gandemer, Mohamed Khettab, Daniel Orbach, Manuel Rodrigues, Sébastien Thureau, Marie Wis
Bulletin du Cancer.2026; 113(1): 8. CrossRef
Beyond EGFR inhibition in head and neck squamous cell carcinoma: Overcoming resistance mechanisms and novel therapeutic frontiers
Francesca Carosi, Daria Maria Filippini, Laura Fabbri, Andrea Carlini, Andrea Monte, Michela Sgarzi, Matteo Fermi, Giulia Querzoli, Donatella Romaniello, Giuseppe Mercante, Achille Tarsitano, Christophe Le Tourneau, Mattia Lauriola
Critical Reviews in Oncology/Hematology.2026; 221: 105207. CrossRef
Prognostic Biomarkers and Immunotherapeutic Insights of Circulating Tumor DNA Analysis in Advanced Esophageal Squamous Cell Carcinoma From SCRUM-MONSTAR GOZILA Substudy
Yuqing Duan, Tadayoshi Hashimoto, Taro Shibuki, Hiroya Taniguchi, Yu Sunakawa, Yoshito Komatsu, Naoki Takahashi, Yuta Sato, Kensei Yamaguchi, Tomohiro Nishina, Tomonori Nakanoko, Shogen Boku, Taroh Satoh, Hisateru Yasui, Taito Esaki, Mitsuho Imai, Takao F
JCO Precision Oncology.2026;[Epub] CrossRef
Driving progress in recurrent and metastatic head and neck cancer: the NRG Oncology perspective
Mercedes Herrera, Matthew Ward, Glenn J Hanna, Sue S Yom, Dwight Heron, Anna Spreafico
JNCI: Journal of the National Cancer Institute.2026;[Epub] CrossRef
PIK3CA Mutations: Are They a Relevant Target in Adult Diffuse Gliomas?
Ana Tomás, Marta Pojo
International Journal of Molecular Sciences.2025; 26(11): 5276. CrossRef

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Lung and Thoracic cancer

Tracing Metastatic Evolutionary Patterns in Lung Adenocarcinoma: Prognostic Dissection Based on a Multi-state Model: Geewon Lee, Yang-Jin Kim, Insuk Sohn, Jong Hoon Kim, Ho Yun Lee; Cancer Res Treat. 2025;57(4):1019-1029. Published online January 24, 2025; DOI: https://doi.org/10.4143/crt.2024.700

Abstract PDF Supplementary Material PubReader ePub

Purpose
After surgery for lung adenocarcinoma, a patient may experience various states of recurrence, with multiple factors potentially influencing the transitions between these states. Our purpose was to investigate the effects of clinical and pathological factors on tumor recurrence, death, and prognosis across various metastasizing pathways.
Materials and Methods
Our study group included 335 patients with all demographic and pathologic data available who underwent surgical resection for lung adenocarcinoma for more than 10 years. The following states of disease were defined: initial state, operation (OP); three intermediate states of local recurrence (LR), metastasis (Meta), and concurrent LR with metastasis (LR+Meta); and a terminal state, death. We identified eight transitions representing various pathways of tumor progression. We employed a multi-state model (MSM) to separate the impacts of multiple prognostic factors on the transitions following surgery.
Results
After surgery, approximately half of patients experienced recurrence. Specifically, 142 (42.4%), 54 (16.1%), and seven (2.1%) patients developed Meta, LR+Meta, and LR, respectively. Clinical and pathological factors associated with the transitions were different. Impact of pathological lymph node remained a risk factor for both OP to Meta (λ02, p=0.001) and OP to LR+Meta (λ03, p=0.001).
Conclusion
Lung adenocarcinoma displays a broad spectrum of clinical scenarios even after curative surgery. Incidence, risk factors, and prognosis varied across different pathways of recurrence in lung adenocarcinoma patients. The greatest implication of this MSM is its ability to predict the timing and type of clinical intervention that will have the greatest impact on survival.

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A‐to‐I RNA Edited miR‐3167 Restrains Malignant Behaviors of Lung Adenocarcinoma by Influencing SSR2‐Meditated Hippo Signaling
Dawei Qian, Dongsheng Zha, Yuanyao Sang, Jiangquan Tao, Bufeng Zhuang, Youshuang Cheng
Molecular Carcinogenesis.2025; 64(9): 1552. CrossRef

3,422 View
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1 Crossref

Lipid Metabolism Related Gene ACSL3 as a Biomarker for Predicting Immunotherapy Outcomes in Lung Adenocarcinoma: Taiping He, Jinhan Hu, Haoyue Guo, Meng Diao, Yuanyuan Wang, Yuhan Wu, Lei Cheng, Chao Zhao, Xuefei Li, Caicun Zhou; Cancer Res Treat. 2025;57(4):1000-1018. Published online January 20, 2025; DOI: https://doi.org/10.4143/crt.2024.1119

Abstract PDF Supplementary Material PubReader ePub

Purpose
Investigate the role of lipid metabolism in the tumor immune microenvironment (TIME) of lung adenocarcinoma (LUAD) and identify vital lipid metabolism-related genes (LMRGs) that contribute to immunotherapy outcomes.
Materials and Methods
One thousand one hundred thirty LUAD patients were acquired utilizing public databases. Multiple algorithms were used to analyze the contribution of lipid metabolism in TIME. Importantly, cell lines, clinical samples (52 patients in surgery cohort and 36 in immunotherapy cohort), animal models, RNA sequencing (RNA-seq), experiments in protein and mRNA levels were conducted for identifying and validating key biomarker in LUAD immunotherapy.
Results
A prognostic signature comprising 33 LMRGs was developed and validated as an effective predictor of prognosis and TIME, with a C-index of 0.766 (95% confidence interval, 0.729 to 0.804). Additionally, we identified acyl-CoA synthetase long-chain family member 3 (ACSL3) as a potential biomarker for immunotherapy prognosis. The expression of ACSL3 was verified in 88 clinical tissues from LUAD patients, which indicated that elevated ACSL3 expression was correlated with worse progression-free survival (p < 0.001) and overall survival (p=0.008). Subsequent experiments revealed that knockdown of ACSL3 in vivo enhanced the efficacy of immunotherapy, potentially through increasing interferon-α secretion, as indicated by bulk RNA-seq and enzyme-linked immunosorbent assay analysis, thereby promoting the infiltration of antitumor immune cells.
Conclusion
The study established a model that accurately predicts immunotherapy response, prognosis, and TIME dynamics in LUAD patients. Notably, the pivotal role of ACSL3 in driving tumor progression and immune evasion was uncovered, offering novel insights into the optimization of immunotherapy strategies for LUAD.

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The multifaceted roles of the ACSL family in cancer: Metabolic reprogramming, ferroptosis regulation and tumour immune microenvironment remodelling
Haocai Li, Weijian Wang, Juncheng Zhan, Yuxiang Xiao, Xiaoping Chen, Chen Su, Peng Zhu
Clinical and Translational Medicine.2026;[Epub] CrossRef
Lipid Metabolism Reprogramming in Cancer: Insights into Tumor Cells and Immune Cells Within the Tumor Microenvironment
Rundong Liu, Chendong Wang, Zhen Tao, Guangyuan Hu
Biomedicines.2025; 13(8): 1895. CrossRef
Independent validation of lung adenocarcinoma prognostic risk scores incorporating cholesterol and estrogen metabolism related transcriptional biomarkers
Qian Zhu, Yuemei Zhang, Jian Ma, Yongjia Li, Hongya Liu, Zhongwen Gong, Ming Du, Xuemei Lian
Scientific Reports.2025;[Epub] CrossRef
Long-chain acyl-CoA synthetases: biological functions, diseases and therapeutic targets
Xiaoliang Deng, Yanqun Luo, Ying Gao, Tao Wu
Molecular Biomedicine.2025;[Epub] CrossRef

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The Synergistic Effect of PARP Inhibitors and Irinotecan in Small Cell Lung Cancer Cells: Songji Oh, Soyeon Kim, Bhumsuk Keam, Jeonghwan Youk, Tae Min Kim, Dong-Wan Kim, Miso Kim; Cancer Res Treat. 2025;57(4):1040-1050. Published online January 7, 2025; DOI: https://doi.org/10.4143/crt.2024.728

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study focused on combining irinotecan with poly(ADP-ribose) polymerase (PARP) inhibitors to explore the potential for novel combination therapeutics in small cell lung cancer (SCLC).
Materials and Methods
We selected 10 different SCLC cell lines with diverse mutational backgrounds in DNA damage response (DDR) pathway genes to evaluate the efficacy of the combination of three PARP inhibitors and irinotecan. After the cells were exposed to the drugs for 7 days, cell viability was measured, and a combination index was calculated. Apoptotic signaling was assessed via western blot, and DNA damage was evaluated using an alkaline comet assay.
Results
We assessed the synergistic effects of PARP inhibitors and irinotecan in in vitro SCLC models, which revealed increased sensitivity, particularly in cells harboring BRCA mutations. However, even in cells lacking mutations in DDR pathway genes, the combination of the two drugs exhibited a synergistic effect. When treated with 50 nM irinotecan, the IC₅₀ fold changes for PARP inhibitors were as follows: olaparib, 1,649±4,049; talazoparib, 25±34.21; venadaparib, 336±596.01. This combination enhanced apoptosis signaling and increased p-chk1 and p-p53 protein levels. Additionally, the treatment of PARP inhibitor with irinotecan increased DNA damage, as visualized by the alkaline comet assay.
Conclusion
This study provides preclinical evidence of the potential clinical benefits of combining irinotecan with PARP inhibitors in SCLC. Further clinical investigations are warranted to validate these findings for the development of more effective and personalized therapeutic strategies for SCLC patients.

4,398 View
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Long-term Survival Outcomes of Surgical Resection for Lung Adenocarcinoma with Intraoperatively Diagnosed Pleural Metastasis: Target Treatment Era: Yelee Kwon, Jae Kwang Yun, Geun Dong Lee, Se Hoon Choi, Yong-Hee Kim, Hyeong Ryul Kim; Cancer Res Treat. 2025;57(4):981-988. Published online December 30, 2024; DOI: https://doi.org/10.4143/crt.2024.993

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aimed to evaluate the clinical impact of main tumor resection on long-term survival compared with pleural biopsy alone in patients with lung adenocarcinoma who were intraoperatively diagnosed with pleural metastasis.
Materials and Methods
A total of 176 patients with adenocarcinoma who had unexpected pleural metastasis detected during surgery from 2002 to 2021 were retrospectively analyzed. Each surgeon decided whether to perform main tumor resection or pleural biopsy alone.
Results
The patients were grouped based on the surgical approaches: main tumor resection (resection group; n=83) and pleural biopsy only (O&C group; n=93). The resection group had better overall survival (OS; 10-year survival, 27.9% vs. 9.4%; median survival, 68.3 vs. 36.6 months; p < 0.01) and locoregional progression-free survival (10-year survival, 12.5% vs. 7.1%; median survival, 19.6 vs. 10.6 months; p < 0.01) than the O&C group. Similar results were found for OS in patients who received tyrosine kinase inhibitors (TKIs) as first-line therapy (10-year survival, 49.2% vs. 15.0%; median survival, 72.2 vs. 45.4 months; p=0.03), patients who did not undergo TKIs treatment (10-year survival, 29.4% vs. 9.2%; median survival, 82.4 vs. 23.8 months; p < 0.01), and patients with positive target gene mutation (10-year survival, 31.7% vs. 10.1%; median survival, 72.2 vs. 33.7 months; p < 0.01). In multivariate analysis, pleural biopsy only (hazard ratio, 1.73; p=0.04) was a significant predictor of OS.
Conclusion
Main tumor resection can improve survival in patients with lung adenocarcinoma who had unexpected pleural metastasis during operation.

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Genitourinary cancer

Pemetrexed Maintenance versus Observation in Patients with Advanced Urothelial Carcinoma Who Completed First-Line Platinum-Based Chemotherapy without Disease Progression (PREMIER, KCSG GU16-05): Inkeun Park, Shinkyo Yoon, Ilhwan Kim, Kwonoh Park, Suee Lee, Bhumsuk Keam, Joo-Hwan Park, Jin Young Kim, Yoon Ji Choi, Byeong Seok Sohn, Jae Lyun Lee; Cancer Res Treat. 2025;57(4):1167-1177. Published online December 27, 2024; DOI: https://doi.org/10.4143/crt.2024.1003

Abstract PDF PubReader ePub: Purpose
Platinum-based chemotherapy is the standard treatment for advanced urothelial carcinoma (aUC). Switch maintenance therapy after first-line (1L) treatment may delay disease progression. This study evaluated pemetrexed as switch maintenance therapy versus observation in aUC patients without disease progression after initial chemotherapy.
Materials and Methods
Eligible aUC patients who did not progress after 4-6 cycles of cisplatin or carboplatin-based chemotherapy were randomized 1:1 to receive maintenance pemetrexed (500 mg/m² intravenously every 3 weeks, up to 16 cycles) or observation. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), response rate, and safety.
Results
The trial was closed early due to slow accrual after avelumab approval. From October 2016 to December 2022, 97 patients were randomized to pemetrexed (n=49) or observation (n=48). The median age was 69 years (range, 43 to 90) and 66 (range, 33 to 82), respectively, with 63% and 73% of patients being male, respectively. The median PFS was 6.0 months (95% confidence interval [CI], 3.4 to 8.5) with pemetrexed versus 2.3 months (95% CI, 1.8 to 2.7) with observation (p=0.044; hazard ratio [HR], 0.64; 95% CI, 0.41 to 0.99). The median OS was 18.1 months (95% CI, 6.9 to 29.4) for pemetrexed and 17.9 months (95% CI, 16.1 to 19.7) for observation (p=0.913; HR, 1.03; 95% CI, 0.61 to 1.73). Common adverse events in the pemetrexed group included anemia (30.6%), fatigue (18.4%), and neutropenia (12.2%), primarily grade 1 or 2.
Conclusion
The PREMIER trial showed that switch maintenance pemetrexed significantly prolonged PFS in aUC patients post-1L platinum-based chemotherapy, with a favorable safety profile. Further studies on combination maintenance therapies are warranted.

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Gastrointestinal cancer

Role and Effectiveness of Hypofractionated Proton Beam Therapy and Combinations with Systemic Chemotherapy in Inoperable Extrahepatic Cholangiocarcinoma: Sung Uk Lee, Tae Hyun Kim, Sang Myung Woo, Jung Won Chun, Hyunjae Shin, Yu Ri Cho, Bo Hyun Kim, Young-Hwan Koh, Sang Soo Kim, Yang-Gun Suh, Sung Ho Moon, Woo Jin Lee; Cancer Res Treat. 2025;57(3):852-864. Published online December 17, 2024; DOI: https://doi.org/10.4143/crt.2024.805

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aims to assess the clinical outcomes of hypofractionated proton beam therapy (PBT) for extrahepatic cholangiocarcinoma (EHCC) and to investigate the optimal sequencing for combining PBT with chemotherapy.
Materials and Methods
We retrospectively analyzed 59 consecutive patients with inoperable EHCC treated with PBT. The median prescribed dose of PBT was 50 GyE (range, 45 to 66 GyE) in 10 fractions. The combination sequences of PBT and chemotherapy were categorized as ‘Pre-PBT chemo’ (chemotherapy before PBT), ‘Post-PBT chemo’ (chemotherapy after PBT), and ‘No pre-/post-PBT chemo’ (no chemotherapy before or after PBT). Overall survival (OS), progression-free survival (PFS), and local PFS were estimated using the Kaplan-Meier method.
Results
All patients completed the planned treatments without any interruptions, and ≥ grade 3 acute adverse events were noted in 1.6% of the cases. The 1-year and 2-year freedom from local progression (FFLP) rates were 86.1% and 66.4%, respectively, with a median time of FFLP of 30.9 months. The 1- and 2-year OS rates were 74.5% and 25.3%, respectively, with a median survival time of 16.7 months. For prognostic factor analysis, pre- or post-PBT chemo was associated with a significantly reduced hazard ratio of 0.473 (95% confidence interval, 0.233 to 0.959; p=0.038) in the multivariate analysis. The median OS times for the groups receiving no pre-/post-PBT chemo, pre-PBT chemo, and post-PBT chemo were 14.6, 18.2, and 21.8 months, respectively (p < 0.05 for each).
Conclusion
Hypofractionated PBT for inoperable EHCC has demonstrated promising FFLP and OS rates with a safe toxicity profile. The combination of PBT with chemotherapy shows potential to improve clinical outcomes.

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Head and Neck cancer

Phase II Trial of Neoadjuvant Docetaxel/Cisplatin/5-Fluorouracil Combined with Pegteograstim for Unresectable, Locally Advanced Sinonasal Squamous Cell Carcinoma: KCSG HN18-07: Bhumsuk Keam, Ho Jung An, Seong Hoon Shin, Min Kyoung Kim, Jung Hae Cho, Seyoung Seo, Sung-Bae Kim; Cancer Res Treat. 2025;57(3):701-708. Published online December 16, 2024; DOI: https://doi.org/10.4143/crt.2024.1025

Abstract PDF Supplementary Material PubReader ePub: Purpose
The role of neoadjuvant chemotherapy in locally advanced sinonasal squamous cell carcinoma (SNSCC) has not been established prospectively. We conducted a phase II trial of neoadjuvant chemotherapy (NAC) with docetaxel/cisplatin/5-fluorouracil (TPF) in this population.
Materials and Methods
Eligible patients had unresectable, locally advanced SNSCC, defined as T3/4 category or potential compromise of critical organ function on surgery. Three TPF (docetaxel 75 mg/m2 and cisplatin 75 mg/m2 on day 1, 5-fluorouracil 1,000 mg/m2 on days 1-4 every 3 weeks) cycles were administered with prophylactic pegteograstim. The primary outcome was the objective response rate (ORR); the secondary outcomes included 2-year progression-free survival (PFS), eyeball preservation rate, and safety.
Results
Among 28 patients screened, 25 were evaluable for efficacy (one screen-failure; two evaluable for safety only). The confirmed ORR was 72.0%. The definitive post-NAC treatment comprised chemoradiotherapy (n=15) and surgery (n=10). With a median follow-up of 25.5 months, median PFS was not reached and the 2-year PFS rate was 60.4%. Response to NAC was related to prolonged PFS (p=0.038). No patient underwent eyeball exenteration at the data cutoff point. Treatment-related adverse events of grade ≥ 3 were neutropenia (48.1%) including febrile neutropenia (14.8%), followed by acute kidney injury (22.2%), nausea/vomiting (11.1%), anemia (7.4%), thrombocytopenia (7.4%), and enterocolitis (3.7%).
Conclusion
TPF NAC showed a promising efficacy and might help preserve critical structures in this population, which needs to be validated in a large prospective trial (KCT0003377).

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Lung and Thoracic cancer

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; Cancer Res Treat. 2025;57(3):720-730. Published online December 3, 2024; DOI: https://doi.org/10.4143/crt.2024.679

Abstract PDF Supplementary Material PubReader ePub

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.

Citations

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circ_PPAPDC1A is Associated with Brain Metastasis of Non-Small-Cell Lung Cancer via the miR-30a-3p/SPOCK1 Pathway
Fang-wen Zou, Sheng-hao Shi, Chenhao Wu, Zhe-ming Zhang, Cong Liu, Yun-fei Li, Shun Xu, Shi-Ze Yang, Zheng-hua Liu
Annals of Surgical Oncology.2026; 33(2): 1760. CrossRef
Characteristics and Treatment Advances of Postoperative Brain Metastasis in Different Lung Cancer Histological Types
Changming Dong, Xuebin Yu, Wuqiao Bao
Current Problems in Surgery.2025; : 101785. CrossRef

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Gastrointestinal cancer

Predictive Value of the nProfiler 1 Assay for the Efficacy of Adjuvant S-1–Based Doublet Chemotherapy in Stage III Gastric Cancer: A Post-Hoc Analysis of a Randomized Phase III Trial: Dong Ki Lee, Choong-kun Lee, Hyo Song Kim, Sun Jin Sym, Dae Young Zang, Ki Hyang Kim, Joo Han Lim, Hae Su Kim, Kyung Hee Lee, Heon Yung Gee, Sun Young Rha, Hyunki Kim, Minkyu Jung; Cancer Res Treat. 2025;57(3):770-780. Published online November 12, 2024; DOI: https://doi.org/10.4143/crt.2024.705

Abstract PDF Supplementary Material PubReader ePub: Purpose
The nProfiler 1 Stomach Cancer Assay (nProfiler1), designed to predict responses to fluorouracil-based adjuvant chemotherapy, measures the expression of four gastric cancer target genes (GZMB, WARS, SFRP4, and CDX1). The randomized phase III POST trial aimed to compare the efficacies of two adjuvant S-1-based doublet chemotherapies: S-1 plus cisplatin (SP) and S-1 plus docetaxel (DS). This study aimed to validate the nProfiler1 assay using a distinct cohort from the POST trial.
Materials and Methods
The nProfiler1 assay stratifies patients into three groups (low-risk, intermediate-risk, and high-risk) using the prognostic single-patient classifier and two groups (chemotherapy-benefit and no-benefit) using the predictive single-patient classifier. The nProfiler1 assay was applied to formalin-fixed paraffin-embedded slides obtained from the POST trial. Disease-free survival (DFS) and overall survival (OS), including 5-year survival rates, were calculated for the enrolled patients.
Results
Of the 153 patients in the POST trial, 118 were included in the post-hoc analysis. With a median follow-up of 57.9 months, no significant difference in DFS or OS was observed between the SP and DS groups. The prognostic single-patient classifier predicted the OS in the SP group (p=0.043) but not in the DS group (p=0.594). The chemotherapy-benefit group exhibited numerically longer DFS than the no-benefit group in the SP and DS groups.
Conclusion
The nProfiler1 assay offers valuable insights into the prognosis and efficacy of adjuvant chemotherapy based on fluorouracil plus platinum doublet regimens but not docetaxel-containing regimens. Further validation with larger patient cohorts and different regimens is warranted.

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