Cancer Research and Treatment

Original Articles

Longitudinal Circulating Tumor DNA Profiling as a Biomarker for Response and Resistance in Platinum-Refractory Head and Neck Squamous Cell Carcinoma: Wonyoung Choi, Jong-Ho Lee, Junsun Ryu, Sung Weon Choi, Yuh-Seog Jung, Joo-Yong Park, Chang Hwan Ryu, Sung Yong Choi, Weon Seo Park, Sun-Young Kong, Tak Yun; Received October 5, 2025 Accepted November 3, 2025 Published online November 4, 2025; DOI: https://doi.org/10.4143/crt.2025.1089 [Accepted]

Abstract PDF: Purpose
Immune checkpoint inhibitors (ICIs) are the standard treatment for platinum-refractory head and neck squamous cell carcinoma (HNSCC). This study aimed to characterize genomic alterations, monitor dynamic changes in circulating tumor DNA (ctDNA) associated with treatment response, and identify novel alterations linked to resistance through serial ctDNA profiling.
Materials and Methods
Patients with platinum-refractory HNSCC receiving nivolumab were enrolled. ctDNA was analyzed using FoundationOne Liquid CDx at baseline, 6 weeks after treatment, and at disease progression.
Results
A total of 36 patients were enrolled, and 33 were evaluable for ctDNA. The most frequent baseline alterations were TP53 (75.8%), followed by TERT (27.3%), NOTCH1 (24.2%), CDKN2A (12.1%), and CCND1 (12.1%). Of 27 patients with measurable lesions, 5 achieved a partial response with a response rate of 18.5%. Dynamic ctDNA profiling revealed all responders had marked reductions in both the sum of variant allele frequencies (sumVAF) and the maximum variant allele frequencies (maxVAF) across detected mutations. A decrease in sumVAF or maxVAF correlated with longer treatment durations, and patients with a >50% decrease in either sumVAF or maxVAF showed significantly longer progression-free survival. Additionally, serial profiling identified de novo mutations in 17 patients, detected during stable disease or progression.
Conclusion
Serial ctDNA analysis provides a noninvasive tool for monitoring treatment response and detecting emerging resistance in HNSCC treated with ICIs. A significant reduction in ctDNA at 6 weeks was associated with improved clinical outcomes and warrants validation in larger, prospective studies to define its role as a predictive biomarker in HNSCC.

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Predictive Role of Baseline Peripheral Lung SUVmax on PET/CT for Immune-Related Pneumonitis and Adverse Events in Lung Cancer Patients Treated with Immune Checkpoint Inhibitors: Kun Ho Kim, Seong Min Kim, Jeong Eun Lee, Song Soo Kim, Da Hyun Kang, Chaeuk Chung; Received May 22, 2025 Accepted October 22, 2025 Published online October 28, 2025; DOI: https://doi.org/10.4143/crt.2025.548 [Accepted]

Abstract PDF: Purpose
Immune checkpoint inhibitors (ICIs) offer durable responses in lung cancer patients lacking actionable mutations or with resistance to prior therapies. However, predicting their efficacy and associated immune-related adverse events (irAEs), such as severe pneumonitis, remains a clinical challenge. This study investigated the predictive value of positron emission tomography/computed tomography (PET/CT)-derived metabolic parameters for pneumonitis and other irAEs in lung cancer patients treated with ICIs.
Materials and Methods
We retrospectively analyzed 151 patients with advanced non-small cell lung cancer (NSCLC) who received ICIs as first-line treatment, either as monotherapy or in combination. Pre-treatment PET/CT was used to measure SUVmax at the primary tumor, tumor-uninvolved peripheral lung, and metastatic sites. Pneumonitis and irAEs were assessed using clinical and radiological findings.
Results
Pneumonitis, severe pneumonitis (grade ≥3), and irAEs occurred in 26.5%, 19.9%, and 37.1% of patients, respectively. A peripheral SUVmax cutoff of >1.1 significantly predicted pneumonitis (area under the curve [AUC] = 0.720, p <0.001). High peripheral SUVmax was associated with higher rates of pneumonitis (42.9% vs. 12.3%, p <0.001), severe pneumonitis (31.4% vs. 9.9%, p=0.001), and irAEs (46.4% vs. 29.5%, p=0.038). In multivariate analysis, high peripheral SUVmax independently predicted pneumonitis (odds ratio [OR]: 4.621; 95% confidence interval [CI]: 1.868–11.431; p=0.001), severe pneumonitis (OR: 2.848; 95% CI: 1.043–7.779; p=0.041), and irAEs (OR: 2.509; 95% CI: 1.114–5.504; p=0.022).
Conclusion
Baseline peripheral SUVmax on PET/CT may serve as a noninvasive biomarker for predicting immune-related pneumonitis and other irAEs in NSCLC patients receiving ICIs, supporting early risk identification.

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Analysis of T Cell Subsets Using Multiplex Immunohistochemistry and Clinical Outcomes of Immune Checkpoint Inhibitors in Advanced Gastric Cancer Patients: Tae-Yong Kim, Jeesun Yoon, Dae-Won Lee, Yoonjin Kwak, Hye Seung Lee, Do-Youn Oh; Received April 28, 2025 Accepted September 7, 2025 Published online September 9, 2025; DOI: https://doi.org/10.4143/crt.2025.458 [Accepted]

Abstract PDF: Purpose
As immunotherapy has become essential in the treatment of gastric cancer (GC), there has been growing interest in T-cells, which play a key role in immunotherapy. In this study, we evaluated the impact of T-cell subsets on immune responsiveness to immune checkpoint inhibitors (ICIs) in GC using multiplex immunohistochemistry (mIHC).
Materials and Methods
Eighty-four GC patients treated with ICIs were enrolled, and we repeated the staining-scanning-stripping procedure nine times to assess different kinds of T-cells or cell-surface immune checkpoints in a single tissue section.
Results
The proportions of patients with microsatellite instability-high (MSI-H), Epstein-Barr virus (EBV), and non-MSI/non-EBV were 8.3%, 3.6% and 88.1%. A high cytotoxic T-cell (T_cyto) density was related to longer overall survival (OS). GC with a high ratio of T_cyto/total T-cells (T_total) and a low ratio of regulatory T-cells (T_reg)/T_total showed better OS. A high density of PD-1- or TIM-3- expressing T_cyto were also associated with longer OS than a low density of those. Among memory T-cells (T_mem) subsets, GC with a high ratio of memory T_cyto/T_mem and a low ratio of memory T_reg/T_mem showed prolonged OS. Better tumor responses were observed in GC with a high ratio of T_cyto/T_total and memory T_cyto/T_mem.
Conclusion
T-cell subsets within the tumor microenvironment were associated with the clinical efficacy of ICIs in GC. PD-1- or TIM-3 expressing T-cells were also associated with response to ICIs, while memory T-cells subsets were associated with survival. mIHC is a feasible method for evaluating T-cell subsets in archival gastric tumor tissue.

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Clinicopathological Factors Influencing PD-L1 Expression and The Effect of Immune Checkpoint Inhibitors on Survival Outcomes in Patients with Gastric Cancer Depending on Sex in a Tertiary Hospital in South Korea: Jeong hwan Lee, Nayoung Kim, Ji-Hyun Kim, Hyeon Jeong Oh, Yeejin Kim, Yonghoon Choi, Hyemin Jo, Ho-Kyoung Lee, Jinju Choi, Yu Kyung Jun, Hyuk Yoon, Cheol Min Shin, Young Soo Park, Dong Ho Lee, Hye Seung Lee, So Hyun Kang, Young Suk Park, Sang-Hoon Ahn, Yun-Suhk Suh, Do Joong Park, Hyung Ho Kim, Ji-Won Kim, Jin Won Kim, Keun-Wook Lee, Won Chang, Yoon Jin Lee, Kyoung Ho Lee, Young Hoon Kim, Soyeon Ahn; Received January 31, 2025 Accepted August 5, 2025 Published online August 13, 2025; DOI: https://doi.org/10.4143/crt.2025.126 [Accepted]

Abstract PDF: Purpose
Programmed cell death ligand-1 (PD-L1) negatively regulates T-cell activation, and exhibits sex-based differences in expression and immune responses. This study investigated sex-related differences in clinicopathological factors influencing PD-L1 expression and the effect of immune checkpoint inhibitors (ICIs) on survival in gastric cancer (GC) patients in South Korea.
Materials and Methods
We analyzed a prospective cohort of 468 GC patients who underwent PD-L1 immunohistochemistry. Age, tumor characteristics, molecular features, and survival outcomes were compared by sex. Multivariate analyses, including Cox proportional hazards modeling with an interaction term for sex, were performed.
Results
Among 468 patients, 280 (59.8%) were PD-L1 positive. In the overall cohort, PD-L1 positivity was significantly associated with Epstein-BarrVirus (EBV) infection (odd ratio [OR]=7.46, p<0.001), antral location of GC (OR=1.84, p=0.027), and macrosatellite instability-High (MSI-H) (OR=5.04, p=0.027). Diffuse-type histology was inversely associated (OR=0.22, p=0.041). In males, EBV (OR=36.27) and antral location (OR=2.38) were significant. In females, only MSI-H was significant (OR=11.63). ICI-containing therapy significantly improved survival in males (p=0.012) but not in females (p=0.415). Cox regression showed a survival benefit from ICIs (HR=0.70, p=0.080), with a borderline-significant interaction by sex (p=0.073).
Conclusion
PD-L1 expression and therapeutic efficacy of ICIs differ by sex in GC. EBV infection and antral tumor location were independent factors in males, while MSI-H status was significant in females. These findings highlights the importance of sex-based immunobiology in tailoring GC treatment strategies.

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Characteristics of Immune Checkpoint Inhibitor (ICI)-Related Hepatotoxicity Based on the Baseline Liver Function: Won-Jung Jung, Eun-Jung Jo, Ye-Jee Kim, Mihyun Park, Eunji Kim, Yu-Seon Jung, Sook Ryun Park, Ji Seon Oh, So-Hui Kim, Jeongbin Park, Sun-Young Jung, Nakyung Jeon; Received January 9, 2025 Accepted July 17, 2025 Published online July 18, 2025; DOI: https://doi.org/10.4143/crt.2025.040 [Accepted]

Abstract PDF Supplementary Material: Purpose
This study estimated the incidence of immune checkpoint inhibitor-related hepatotoxicity (ICH), identified risk factors, and characterized patients who developed ICH.
Materials and Methods
Adult patients treated with ICIs from January 2015 to June 2022 in a tertiary hospital were included, excluding those without liver function tests or those with liver cancer but normal baseline liver function. Patients were stratified by baseline liver function status; in overall and each of stratified cohorts ICH incidence was calculated as the number of events per 100 person-years with grade 3 hepatotoxicity as the primary outcome. Patient characteristics were assessed using descriptive statistics, and risk factors were identified through multivariable Cox regression. Causality between ICI use and hepatotoxicity was assessed using the Naranjo Algorithm.
Results
Among 803 patients, the ICH incidence was 19.5 cases per 100 person-years, with a higher incidence (47.3 vs. 9.3 cases per 100 person-years) and earlier onset (13 vs. 15 days) in the abnormal compared to the normal group. Significant risk factors for ICH included female sex in the normal group and liver cancer in the abnormal group. According to the Naranjo Algorithm, all the 60 ICH cases were classified as “probable” or “possible”. Among the 60 cases, 62% (n=37) resulted in ICI discontinuation. The baseline liver function did not impact on the severity or the likelihood of ICI discontinuation.
Conclusion
Future studies are needed to evaluate whether the impact of ICI discontinuation on survival outcomes in patients with ICH varies based on baseline liver function abnormalities.

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Programmed Death-Ligand 1 Expression Across Multiple Assays in Ovarian Cancer: A Comparative Analysis: Eun Bi Jang, Kyeong A So, Wook Youn Kim, So Dug Lim, Tae Jin Kim, Heejin Bang, Wan Seop Kim; Received February 21, 2025 Accepted June 5, 2025 Published online June 9, 2025; DOI: https://doi.org/10.4143/crt.2025.202 [Accepted]

Abstract PDF: Purpose
Ovarian cancer presents significant treatment challenges due to its aggressive nature and poor response to immune checkpoint inhibitors (ICIs). The lack of standardized programmed cell death-ligand 1 (PD-L1) assays and cut-off values complicates clinical decision-making. We evaluated the concordance among commonly used PD-L1 assays and assessed changes in the expression of PD-L1 following chemotherapy.
Materials and Methods
Tissue samples from 29 patients with ovarian cancer were analyzed using five validated PD-L1 immunohistochemistry assays: Dako 22C3, Ventana SP263, Ventana SP142, Dako 28-8, and Ventana 22C3. PD-L1 positivity was assessed using a combined positive score (CPS), immune cell (IC), or tumor proportion score (TPS) at 1%, 5%, and 10% cut-offs. Concordance rates, including overall percent agreement (OPA) and Cohen’s kappa coefficient, were analyzed. In addition, changes in the expression of PD-L1 pre- and post-chemotherapy were evaluated.
Results
Positivity rates ranged from 15.8% (SP142) to 29.8% (Dako 22C3 and SP263) at the 1% CPS cut-off. SP142 consistently exhibited the lowest concordance, whereas Dako 22C3 displayed high agreement with SP263, 28-8, and Ventana 22C3. Chemotherapy increased PD-L1 positivity, with 28% of patients converting from negative to positive.
Conclusion
The expression of PD-L1 in ovarian cancer varies across assays and scoring methods, emphasizing the need for standardized testing protocols. Increased PD-L1 expression post-chemotherapy underscores the importance of assessing its status at appropriate times to guide ICI therapy. Larger studies are required to validate these findings and refine clinical applications.

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Lung and Thoracic cancer

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; Cancer Res Treat. 2025;57(2):422-433. Published online October 30, 2024; DOI: https://doi.org/10.4143/crt.2024.493

Abstract PDF Supplementary Material PubReader ePub

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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Effects of Sarcopenia on the Outcomes and Safety of Chemoradiotherapy Followed by Durvalumab for the Treatment of Patients With Locally Advanced Non‐Small Cell Lung Cancer
Kentaro Tamura, Hidehito Horinouchi, Mototaka Miyake, Ken Masuda, Yuki Shinno, Yusuke Okuma, Tatsuya Yoshida, Noboru Yamamoto, Yasushi Goto
Thoracic Cancer.2025;[Epub] CrossRef

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Hematologic malignancy

Nivolumab in Relapsed or Refractory Primary Central Nervous System Lymphoma: Multicenter, Retrospective Study: Jun Ho Yi, Seok Jin Kim, Sang-A Kim, Jongheon Jung, Dok Hyun Yoon; Cancer Res Treat. 2025;57(2):590-596. Published online August 16, 2024; DOI: https://doi.org/10.4143/crt.2024.531

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Purpose
Given that 40%-50% of primary central nervous system lymphoma (PCNSL) tissues exhibit aberrancy on 9p24.1, immune checkpoint inhibitors (ICI) may work for the disease.
Materials and Methods
To define the role of ICIs in PCNSL, we carried out a nationwide retrospect analysis for 22 patients who had been treated with nivolumab monotherapy for relapsed or refractory PCNSL.
Results
The median age at diagnosis was 66, and male: female ratio was 1:1. Patients received nivolumab after a median of 3 lines (range, 2 to 6) of therapy and at the median age of 67 years (range, 37 to 82 years). Eleven patients (50%) were refractory to the last treatment prior to nivolumab. With a median follow-up duration of 22.3 months (95% confidence interval [CI], 13.1 to 31.5), nine patients (41%) had an objective response (6 complete responses, 3 partial responses), and the median duration of response was 20.9 months (95% CI, 1.7 to 40.0). The median progression-free survival and overall survival were 2.1 months (95% CI, 0.2 to 4.0) and 18.9 months (95% CI, 5.0 to 32.8), respectively. Nivolumab was generally well-tolerated as no patients required dose reduction and only two patients required delay of treatment.
Conclusion
Our study suggests that nivolumab can be a reasonable option with the durable response for RR PCNSL.

Citations

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Targeting PD-L1 for PCNS-DLBCL: from molecular effects to clinical translation
Jiajia Cao, Shuzhen Xiong, Shuni Zhang, Ningning Yue, Chongyang Wu
Frontiers in Immunology.2025;[Epub] CrossRef
Relapsed or refractory central nervous system lymphoma successfully treated by glofitamab combined with lenalidomide
Yin-yin Peng, Xiao-qiong Tang
Frontiers in Oncology.2025;[Epub] CrossRef
Immunotherapy in central nervous system tumors
Yutao Huang, Yi Liu, Hui Zeng, JingJing Yang, Zongping Li, Jianguo Xu, Liyuan Jin, Xiaoyin Liu, Liangxue Zhou
International Journal of Surgery.2025; 111(11): 8301. CrossRef

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Lung and Thoracic cancer

Association of TP53 Mutation Status and Sex with Clinical Outcome in Non–Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors: A Retrospective Cohort Study: Songji Choi, Se Hyun Kim, Sejoon Lee, Jeongmin Seo, Minsu Kang, Eun Hee Jung, Sang-A Kim, Koung Jin Suh, Ji Yun Lee, Ji-Won Kim, Jin Won Kim, Jeong-Ok Lee, Yu Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang, Jong Seok Lee; Cancer Res Treat. 2025;57(1):70-82. Published online August 7, 2024; DOI: https://doi.org/10.4143/crt.2024.046

Abstract PDF Supplementary Material PubReader ePub

Purpose
Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC.
Materials and Methods
Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed.
Results
In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT.
Conclusion
Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.

Citations

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Association Between TP53 Mutations and Platinum Resistance in a Cohort of High-Grade Serous Ovarian Cancer Patients: Novel Implications for Personalized Therapeutics
Clelia Madeddu, Eleonora Lai, Manuela Neri, Elisabetta Sanna, Giulia Gramignano, Sonia Nemolato, Mario Scartozzi, Sabrina Giglio, Antonio Macciò
International Journal of Molecular Sciences.2025; 26(5): 2232. CrossRef
Prognostic and predictive implications of tumor suppressor gene alterations in non-small cell lung cancer
Marco Sposito, Lorenzo Belluomini, Riccardo Nocini, Jessica Insolda, Ilaria Mariangela Scaglione, Jessica Menis, Michele Simbolo, Antonio Lugini, Federica Buzzacchino, Francesco Verderame, Francesca Spinnato, Giuseppe Aprile, Lorenzo Calvetti, Mario Occhi
Scientific Reports.2025;[Epub] CrossRef
Enhanced tumor heterogeneity mediates poor prognosis in females with TP53 mutation in lung adenocarcinoma
Liudan Mai, Xinxin Yang, Chen Shao, Hongwei Yu, Fenqi Du, Jialu Liu, Yue Guan, Hao Li, Maopeng Yang, Hongxue Meng, Qiuju Zhang
International Journal of Biological Macromolecules.2025; 334: 149083. CrossRef

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Gastrointestinal cancer

Distinct Characteristics and Changes in Liver Function of Patients with Hepatocellular Carcinoma Treated with Atezolizumab Plus Bevacizumab for More Than 1 Year: Youngun Kim, Jung Sun Kim, Beodeul Kang, Ilhwan Kim, Hyeyeong Kim, Won Suk Lee, Yun Beom Sang, Sanghoon Jung, Chansik An, Chan Kim, Hong Jae Chon; Cancer Res Treat. 2024;56(4):1231-1239. Published online May 27, 2024; DOI: https://doi.org/10.4143/crt.2024.237

Abstract PDF Supplementary Material PubReader ePub

Purpose
Since 2020, atezolizumab plus bevacizumab (Ate/Bev) has been the standard first-line therapy for unresectable hepatocellular carcinoma (HCC), but long-term treatment studies are limited. This study evaluated the clinical characteristics and effects of Ate/Bev for over 1 year.
Materials and Methods
This study included patients with unresectable HCC treated with first-line Ate/Bev between May 2020 and April 2022. Those receiving Ate/Bev for 1 year or more were classified as the long-term treatment group.
Results
Of 246 patients, 69 (28.0%) were in the long-term treatment group, which comprised more proportions of intrahepatic tumor burden < 25%, Eastern Cooperative Oncology Group 0, and a lower proportion of portal vein tumor thrombosis than the short-term treatment group. The long-term treatment group had a higher incidence of atezolizumab-related thyroid dysfunction (31.9% vs. 10.7%, p < 0.001; median time to onset [mTTO], 2.8 months), dermatologic toxicity (29.0% vs. 14.7%, p=0.017; mTTO, 3.3 months), bevacizumab-related hypertension (44.9% vs. 22.0%, p=0.001; mTTO, 4.2 months), and proteinuria (69.6% vs. 38.4%, p < 0.001; mTTO, 6.8 months), compared to the short-term treatment group. Regarding liver function in the long-term treatment group, patients initially classified as Child-Pugh class A decreased from 87.0% to 75.4%, and albumin-bilirubin grade 1 decreased from 68.1% to 50.7% after 1 year of treatment.
Conclusion
The Ate/Bev long-term treatment group had a lower intrahepatic tumor burden, less portal vein tumor thrombosis, and better performance status and liver function at baseline. Atezolizumab-related immunological adverse events emerged relatively early in treatment compared to the bevacizumab-related. Additionally, some patients demonstrated liver function deterioration during long-term Ate/Bev treatment.

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A case of long-term therapy of hepatocellular carcinoma with atezolizumab and bevacizumab combination
K. V. Menshikov, A. V. Sultanbaev, Sh. H. Musin, V. A. Valishin, I. A. Men′shikova, V. S. Chalov, N. I. Sultanbaeva, Sh. N. Galimov
Meditsinskiy sovet = Medical Council.2025; (10): 49. CrossRef

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Sarcoma

Comprehensive Molecular Characterization of Soft Tissue Sarcoma for Prediction of Pazopanib-Based Treatment Response: Jung Yong Hong, Hee Jin Cho, Kum-Hee Yun, Young Han Lee, Seung Hyun Kim, Wooyeol Baek, Sang Kyum Kim, Yurimi Lee, Yoon-La Choi, Minsuk Kwon, Hyo Song Kim, Jeeyun Lee; Cancer Res Treat. 2023;55(2):671-683. Published online September 27, 2022; DOI: https://doi.org/10.4143/crt.2022.251

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Purpose
Even though pazopanib, a multitargeted tyrosine kinase inhibitor, has been approved for refractory soft tissue sarcoma (STS), little is known about the molecular determinants of the response to pazopanib. We performed integrative molecular characterization to identify potential predictors of pazopanib efficacy.
Materials and Methods
We obtained fresh pre-treatment tumor tissue from 35 patients with advanced STS receiving pazopanib-based treatment. Among those, 18 (51.4%) received pazopanib monotherapy, and the remaining 17 (48.6%) received pazopanib in combination with durvalumab, programmed death-ligand 1 blockade. Whole-exome and transcriptome sequencing were performed for each tumor and patient germline DNA.
Results
Of the 35 patients receiving pazopanib-based treatment, nine achieved a partial response (PR), resulting in an objective response rate (ORR) of 27.3%, and the median progression-free survival (PFS) was 6.0 months. Patients with CDK4 amplification (copy ratio tumor to normal > 2) exhibited shorter PFS (3.7 vs. 7.9 months, p=2.09×10–4) and a poorer response (ORR; 0% vs. 33.3%) compared to those without a gene amplification (copy ratio ≤ 2). Moreover, non-responders demonstrated transcriptional activation of CDK4 via DNA amplification, resulting in cell cycle activation. In the durvalumab combination cohort, seven of the 17 patients (41.2%) achieved a PR, and gene expression analysis revealed that durvalumab responders exhibited high immune/stromal cell infiltration, mainly comprising natural killer cells, compared to non-responders as well as increased expression of CD19, a B-cell marker.
Conclusion
Despite the limitation of heterogeneity in the study population and treatment, we identified possible molecular predictors of pazopanib efficacy that can be employed in future clinical trials aimed at evaluating therapeutic strategies.

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Musculoskeletal Diseases: Mechanisms and Therapeutic Advances
Xiao Ma, Eloy Yinwang, Xupeng Chai, Fangqian Wang, Zehao Chen, Shengdong Wang, Hao Zhou, Yucheng Xue, Jiangchu Lei, Fanglu Chen, Hengyuan Li, Shixin Chen, Shenzhi Zhao, Kelei Wang, Liang Chen, Junjie Gao, Zhaoming Ye, Nong Lin
MedComm.2025;[Epub] CrossRef
Durvalumab plus pazopanib combination in patients with advanced soft tissue sarcomas: a phase II trial
Hee Jin Cho, Kum-Hee Yun, Su-Jin Shin, Young Han Lee, Seung Hyun Kim, Wooyeol Baek, Yoon Dae Han, Sang Kyum Kim, Hyang Joo Ryu, Joohee Lee, Iksung Cho, Heounjeong Go, Jiwon Ko, Inkyung Jung, Min Kyung Jeon, Sun Young Rha, Hyo Song Kim
Nature Communications.2024;[Epub] CrossRef
The high-density lipoprotein binding protein HDLBP is an unusual RNA-binding protein with multiple roles in cancer and disease
Jonathan Feicht, Ralf-Peter Jansen
RNA Biology.2024; 21(1): 312. CrossRef
Intracranial Relapse in Pediatric Sarcoma
Danielle E. Smith, Tyler Hamby, Kenneth Heym, Ashraf Mohamed, Kelly L. Vallance, Anish Ray
Journal of Pediatric Hematology/Oncology.2023; 45(7): e810. CrossRef

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Gastrointestinal cancer

Molecular and Immune Profiling of Syngeneic Mouse Models Predict Response to Immune Checkpoint Inhibitors in Gastric Cancer: Dagyeong Lee, Junyong Choi, Hye Jeong Oh, In-Hye Ham, Sung Hak Lee, Sachiyo Nomura, Sang-Uk Han, Hoon Hur; Cancer Res Treat. 2023;55(1):167-178. Published online May 20, 2022; DOI: https://doi.org/10.4143/crt.2022.094

Abstract PDF Supplementary Material PubReader ePub

Purpose
Appropriate preclinical mouse models are needed to evaluate the response to immunotherapeutic agents. Immunocompetent mouse models have rarely been reported for gastric cancer. Thus, we investigated immunophenotypes and responses to immune checkpoint inhibitor (ICI) in immunocompetent mouse models using various murine gastric cancer cell lines.
Materials and Methods
We constructed subcutaneous syngeneic tumors with murine gastric cancer cell lines, YTN3 and YTN16, in C57BL/6J mice. Mice were intraperitoneally treated with IgG isotype control or an anti–programmed death-ligand 1 (PD-L1) neutralizing antibody. We used immunohistochemistry to evaluate the tumor-infiltrating immune cells of formalin-fixed paraffin-embedded mouse tumor tissues. We compared the protein and RNA expression between YTN3 and YTN16 cell lines using a mouse cytokine array and RNA sequencing.
Results
The mouse tumors revealed distinct histological and molecular characteristics. YTN16 cells showed upregulation of genes and proteins related to immunosuppression, such as Ccl2 (CCL2) and Csf1 (M-CSF). Macrophages and exhausted T cells were more enriched in YTN16 tumors than in YTN3 tumors. Several YTN3 tumors were completely regressed by the PD-L1 inhibitor, whereas YTN16 tumors were unaffected. Although treatment with a PD-L1 inhibitor increased infiltration of T cells in both the tumors, the proportion of exhausted immune cells did not decrease in the non-responder group.
Conclusion
We confirmed the histological and molecular features of cancer cells with various responses to ICI. Our models can be used in preclinical research on ICI resistance mechanisms to enhance clinical efficacy.

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The Therapeutic Potential of Targeting Tumor Microenvironment and Modulation of Immunotherapy in Gastrointestinal Cancer
Saeideh Khorshid Sokhangouy, Hamid Jamialahmadi, Mahdieh Sadat Mortazavi Sani, Ghazaleh Khalili-Tanha, Arian Karimi Rouzbahani, Golnaz Mahmoudvand, Zahra Goudarzi, Arshia Fakouri, Simin Farokhi, Seyed Mahdi Hassanian, Gordon A Ferns, Elham Nazari, Amir Av
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Tubulointerstitial nephritis antigen-like 1 from cancer-associated fibroblasts contribute to the progression of diffuse-type gastric cancers through the interaction with integrin β1
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Histopathologic and Molecular Biomarkers of PD-1/PD-L1 Inhibitor Treatment Response among Patients with Microsatellite Instability‒High Colon Cancer: Jaewon Hyung, Eun Jeong Cho, Jihun Kim, Jwa Hoon Kim, Jeong Eun Kim, Yong Sang Hong, Tae Won Kim, Chang Ohk Sung, Sun Young Kim; Cancer Res Treat. 2022;54(4):1175-1190. Published online January 12, 2022; DOI: https://doi.org/10.4143/crt.2021.1133

Abstract PDF Supplementary Material PubReader ePub

Purpose
Recent clinical trials have reported response rates < 50% among patients treated with programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors for microsatellite instability‒high (MSI-H) colorectal cancer (CRC), and factors predicting treatment response have not been fully identified. This study aimed to identify potential biomarkers of PD-1/PD-L1 inhibitor treatment response among patients with MSI-H CRC.
Materials and Methods
MSI-H CRC patients enrolled in three clinical trials of PD-1/PD-L1 blockade at Asan Medical Center (Seoul, Republic of Korea) were screened and classified into two groups according to treatment response. Their histopathologic features and expression of 730 immune-related genes from the NanoString platform were evaluated, and a machine learning–based classification model was built to predict treatment response among MSI-H CRCs patients.
Results
A total of 27 patients (15 responders, 12 non-responders) were included. A high degree of lymphocytic/neutrophilic infiltration and an expansile tumor border were associated with treatment response and prolonged progression-free survival (PFS), while mucinous/signet-ring cell carcinoma was associated with a lack of treatment response and short PFS. Gene expression profiles revealed that the interferon-γ response pathway was enriched in the responder group. Of the top eight differentially expressed immune-related genes, PRAME had the highest fold change in the responder group. Higher expression of PRAME was independently associated with better PFS along with histologic subtypes in the multivariate analysis. The classification model using these genes showed good performance for predicting treatment response.
Conclusion
We identified histologic and immune-related gene expression characteristics associated with treatment response in MSI-H CRC, which may contribute to optimal patient stratification.

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Yang An, Jiaolin Zhou, Lan Su, Lin Cong, Xinxin Mao, Bo Chen, Yuhua Gong, Yaping Xu, Han Chen, Chentong Wang, Guole Lin, Huanwen Wu
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Hannah Yang, Beodeul Kang, Yeonjung Ha, Sung Hwan Lee, Ilhwan Kim, Hyeyeong Kim, Won Suk Lee, Gwangil Kim, Sanghoon Jung, Sun Young Rha, Vincent E. Gaillard, Jaekyung Cheon, Chan Kim, Hong Jae Chon
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Eun‐Jin Go, Hannah Yang, Wooram Park, Seung Joon Lee, Jun‐Hyeok Han, So Jung Kong, Won Suk Lee, Dong Keun Han, Hong Jae Chon, Chan Kim
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Gynecologic cancer

Frequency of Mismatch Repair Deficiency/High Microsatellite Instability and Its Role as a Predictive Biomarker of Response to Immune Checkpoint Inhibitors in Gynecologic Cancers: Joseph J. Noh, Min Kyu Kim, Min Chul Choi, Jeong-Won Lee, Hyun Park, Sang Geun Jung, Won Duk Joo, Seung Hun Song, Chan Lee; Cancer Res Treat. 2022;54(4):1200-1208. Published online December 13, 2021; DOI: https://doi.org/10.4143/crt.2021.828

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study was to investigate the frequency of mismatch repair deficiency/high microsatellite instability (MMRd/MSI-H) in gynecologic malignancies and the efficacy of immune checkpoint inhibitors (ICIs) in patients with recurrent gynecologic cancers according to MMR/MSI status.
Materials and Methods
We conducted a multi-center retrospective review on the patients who were diagnosed with gynecologic cancers between 2015 and 2020. Their clinicopathologic information, results of immunohistochemistry staining for MLH1/MSH2/MSH6/PMS2 and MSI analysis, tumor response to treatment with ICIs were investigated.
Results
Among 1,093 patients included in the analysis, MMRd/MSI-H was most frequent in endometrial/uterine cancers (34.8%, 164/471), followed by ovarian, tubal, and peritoneal cancers (12.8%, 54/422) and cervical cancer (11.3%, 21/186). When assessed by histology without regard for cancer types, the frequency of MMRd/MSI-H was 11.0% (38/345) in high-grade serous adenocarcinoma, 38.6% (117/303) in endometrioid adenocarcinoma, and 30.2% (16/53) in carcinosarcoma. A total of 114 patients were treated with ICIs at least once. The objective response rate (ORR) was 21.6% (8/37) in cervical cancer, 4.7% (2/43) in ovarian cancer, and 25.8% (8/31) in endometrial/uterine cancers. Univariate regression analysis identified MMRd/MSI-H as the only significant factor associated with the ORR (28.9% [11/38] vs. 11.8% [9/76]; odds ratio, 3.033; 95% confidence interval, 1.129–8.144; p=0.028).
Conclusion
The frequency of MMRd/MSI-H is moderate to high in gynecologic cancers in the Korean population. MMRd/MSI-H could be effective predictive biomarkers in gynecologic cancers of any type.

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Guillaume Mestrallet, Matthew Brown, Cansu Cimen Bozkus, Nina Bhardwaj
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Lung and Thoracic cancer

Clinical Efficacy of Immune Checkpoint Inhibitors in Non–Small Cell Lung Cancer Patients with Liver Metastases: A Network Meta-Analysis of Nine Randomized Controlled Trials: Qing Yin, Longguo Dai, Ruizhu Sun, Ping Ke, Liya Liu, Bo Jiang; Cancer Res Treat. 2022;54(3):803-816. Published online October 25, 2021; DOI: https://doi.org/10.4143/crt.2021.764

Abstract PDF Supplementary Material PubReader ePub

Purpose
This network meta-analysis (NMA) was conducted to compare the efficacy of immune checkpoint inhibitors in advanced non–small cell lung cancer (NSCLC) patients with liver metastases.
Materials and Methods
English literature was retrieved from the PubMed, American Society of Clinical Oncology, and European Society for Medical Oncology databases from January 2015 to January 2021. We pooled the overall survival (OS) and progression-free survival (PFS) hazard ratios (HRs) using an NMA and ranked treatments by the surface under the cumulative ranking curve. Publication bias was evaluated by Begg’s and Egger’s tests. STATA 15.0 was used for the sensitivity analysis, and the remaining statistical analyses were performed using R 4.0.2.
Results
Nine eligible phase III randomized controlled trials were included, including 1,141 patients with liver metastases. Pembrolizumab+chemotherapy ranked highest, followed by atezolizumab+bevacizumab+chemotherapy and nivolumab. However, no significant difference in OS rates was observed across these three treatments (HR, 0.98; 95% confidence interval [CI], 0.43 to 2.22 for pembrolizumab+chemotherapy vs. atezolizumab+bevacizumab+chemotherapy; HR, 0.91; 95% CI, 0.52 to 1.57 for pembrolizumab+chemotherapy vs. nivolumab). Regarding the PFS rate, atezolizumab+bevacizumab+chemotherapy and pembro-lizumab+chemotherapy ranked highest and no significant difference was observed between them (HR, 0.79; 95% CI, 0.36 to 1.70 for atezolizumab+bevacizumab+chemotherapy vs. pembrolizumab+chemotherapy).
Conclusion
Pembrolizumab+chemotherapy, atezolizumab+bevacizumab+chemotherapy, and nivolumab were superior to other treatments in NSCLC patients with liver metastases. These new findings may help clinicians better select therapeutic strategies for NSCLC patients with liver metastases.

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Weixing Zhao, Bo Li, Yujia Gu, Xiaoni Jin, Zirui Li, Wanjing Guo, Xinxin Lu, Jun Jiang
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Progress of immune checkpoint inhibitors therapy for non-small cell lung cancer with liver metastases
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Lingling Zhu, Xianzhe Yu, Xiaojun Tang, Chenggong Hu, Lei Wu, Yanyang Liu, Qinghua Zhou
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Treatment Options for Patients with Non-Small Cell Lung Cancer and Liver Metastases
Vesna Ćeriman Krstić, Natalija Samardžić, Milija Gajić, Milan Savić, Biljana Šeha, Marina Roksandić Milenković, Dragana Jovanović
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Histone Deacetylase as a Valuable Predictive Biomarker and Therapeutic Target in Immunotherapy for Non-Small Cell Lung Cancer: Hyun-Seock Shin, Juwhan Choi, Jinhwan Lee, Sung Yong Lee; Cancer Res Treat. 2022;54(2):458-468. Published online September 10, 2021; DOI: https://doi.org/10.4143/crt.2021.425

Abstract PDF Supplementary Material PubReader ePub

Purpose
Histone deacetylase inhibitors (HDACis) are epigenetic regulators and used clinically for hematopoietic malignancies. Recently, HDACis have received attention as a factor that modulates the immune system. In this study, the role of histone deacetylase (HDAC) expression as a predictive marker in lung cancer patients who were treated with immune checkpoint inhibitors (ICIs) and the role of HDACi and ICI combination treatment in the mouse tumor model were analyzed.
Materials and Methods
The overall response rate (ORR) and progression-free survival (PFS) were analyzed by the expression of HDAC. In vitro assay, the mRNA and protein expression levels of cytokines and programmed death-ligand 1 (PD-L1) were analyzed after HDACi treatment. In vivo assay, TC-1 tumor-bearing mice were treated with HDACi and mouse programmed cell death 1 (PD-1) inhibitor.
Results
The HDAC6 low expression group showed high ORR and prolonged PFS. When the selective HDAC6 inhibitor was administered to the A549 cell line, the levels of interleukin-1β and interleukin-6 decreased and the expression of PD-L1 was reduced. Mice that received both the mouse PD-1 inhibitor and pan-HDACi had a smaller tumor size than that of the mice from the control group. Moreover, mice treated with the mouse PD-1 inhibitor and pan-HDACi generated greater numbers of E7-specific CD8+ T cells.
Conclusion
HDAC6 expression can predict the prognosis of non–small cell lung cancerpatients who were treated with ICIs. Furthermore, co-treatment with HDACi and PD-1 inhibitor was shown to decrease the tumor growth rate and create a favorable tumor microenvironment for cytotoxic T lymphocytes in the TC-1 mouse model.

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General

Engineering a High-Affinity PD-1 Peptide for Optimized Immune Cell-Mediated Tumor Therapy: Yilei Chen, Hongxing Huang, Yin Liu, Zhanghao Wang, Lili Wang, Quanxiao Wang, Yan Zhang, Hua Wang; Cancer Res Treat. 2022;54(2):362-374. Published online August 3, 2021; DOI: https://doi.org/10.4143/crt.2021.424

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to optimize a peptide (nABP284) that binds to programmed cell death protein 1 (PD-1) by a computer-based protocol in order to increase its affinity. Then, this study aimed to determine the inhibitory effects of this peptide on cancer immune escape by coculturing improving cytokine-induced killer (ICIK) cells with cancer cells.
Materials and Methods
nABP284 that binds to PD-1 was identified by phage display technology in our previous study. AutoDock and PyMOL were used to optimize the sequence of nABP284 to design a new peptide (nABPD1). Immunofluorescence was used to demonstrate that the peptides bound to PD-1. Surface plasmon resonance was used to measure the binding affinity of the peptides. The blocking effect of the peptides on PD-1 was evaluated by a neutralization experiment with human recombinant programmed death-ligand 1 (PD-L1) protein. The inhibition of activated lymphocytes by cancer cells was simulated by coculturing of human acute T lymphocytic leukemia cells (Jurkat T cells) with human tongue squamous cell carcinoma cells (Cal27 cells). The anticancer activities were determined by coculturing ICIK cells with Cal27 cells in vitro.
Results
A high-affinity peptide (nABPD1, K_D=11.9 nM) for PD-1 was obtained by optimizing the nABP284 peptide (K_D=11.8 μM). nABPD1 showed better efficacy than nABP284 in terms of increasing the secretion of interkeulin-2 by Jurkat T cells and enhancing the in vitro antitumor activity of ICIK cells.
Conclusion
nABPD1 possesses higher affinity for PD-1 than nABP284, which significantly enhances its ability to block the PD-1/PD-L1 interaction and to increase ICIK cell-mediated antitumor activity by armoring ICIK cells.

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Yajing Mi, Pengtao Jiang, Jing Luan, Lin Feng, Dian Zhang, Xingchun Gao
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Lung and Thoracic cancer

Comparison of the Predictive Power of a Combination versus Individual Biomarker Testing in Non–Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors: Hyojin Kim, Hyun Jung Kwon, Eun Sun Kim, Soohyeon Kwon, Kyoung Jin Suh, Se Hyun Kim, Yu Jung Kim, Jong Seok Lee, Jin-Haeng Chung; Cancer Res Treat. 2022;54(2):424-433. Published online July 7, 2021; DOI: https://doi.org/10.4143/crt.2021.583

Abstract PDF Supplementary Material PubReader ePub

Purpose
Since tumor mutational burden (TMB) and gene expression profiling (GEP) have complementary effects, they may have improved predictive power when used in combination. Here, we investigated the ability of TMB and GEP to predict the immunotherapy response in patients with non–small cell lung cancer (NSCLC) and assessed if this combination can improve predictive power compared to that when used individually.
Materials and Methods
This retrospective cohort study included 30 patients with NSCLC who received immune checkpoint inhibitors (ICI) therapy at the Seoul National University Bundang Hospital. programmed cell death-ligand-1 (PD-L1) protein expression was assessed using immunohistochemistry, and TMB was measured by targeted deep sequencing. Gene expression was determined using NanoString nCounter analysis for the PanCancer IO360 panel, and enrichment analysis were performed.
Results
Eleven patients (36.7%) showed a durable clinical benefit (DCB), whereas 19 (63.3%) showed no durable benefit (NDB). TMB and enrichment scores (ES) showed significant differences between the DCB and NDB groups (p=0.044 and p=0.017, respectively); however, no significant correlations were observed among TMB, ES, and PD-L1. ES was the best single biomarker for predicting DCB (area under the curve [AUC], 0.794), followed by TMB (AUC, 0.679) and PD-L1 (AUC, 0.622). TMB and ES showed the highest AUC (0.837) among other combinations (AUC [TMB and PD-L1], 0.777; AUC [PD-L1 and ES], 0.763) and was similar to that of all biomarkers used together (0.832).
Conclusion
The combination of TMB and ES may be an effective predictive tool to identify patients with NSCLC patients who would possibly benefit from ICI therapies.

Citations

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Microdroplet-enhanced chip platform for high-throughput immunotherapy marker screening from extracellular vesicle RNAs and membrane proteins
Chuanhao Tang, Zaizai Dong, Shi Yan, Bing Liu, Zhiying Wang, Long Cheng, Feng Liu, Hong Sun, Yimeng Du, Lu Pan, Yuhao Zhou, Zhiyuan Jin, Libo Zhao, Nan Wu, Lingqian Chang, Xiaojie Xu
Biosensors and Bioelectronics.2025; 267: 116748. CrossRef
Visualising the Truth: A Composite Evaluation Framework for Score-Based Predictive Model Selection
Uraquitan Lima Filho, Tiago Alexandre Pais, Ricardo Jorge Pais
BioMedInformatics.2025; 5(3): 55. CrossRef
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Evaluation of Blood Tumor Mutation Burden for the Efficacy of Second-Line Atezolizumab Treatment in Non-Small Cell Lung Cancer: BUDDY Trial
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Cells.2023; 12(9): 1246. CrossRef
Unveiling the role of regulatory T cells in the tumor microenvironment of pancreatic cancer through single-cell transcriptomics and in vitro experiments
Wei Xu, Wenjia Zhang, Dongxu Zhao, Qi Wang, Man Zhang, Qiang Li, Wenxin Zhu, Chunfang Xu
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Facilitating “Omics” for Phenotype Classification Using a User-Friendly AI-Driven Platform: Application in Cancer Prognostics
Uraquitan Lima Filho, Tiago Alexandre Pais, Ricardo Jorge Pais
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Current state and challenges of emerging biomarkers for immunotherapy in hepatocellular carcinoma (Review)
Mo Cheng, Xiufeng Zheng, Jing Wei, Ming Liu
Experimental and Therapeutic Medicine.2023;[Epub] CrossRef

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Rare Cancer

Clinical Experience of Male Primary Choriocarcinoma at the Samsung Medical Center: Young Sok Ji, Se Hoon Park; Cancer Res Treat. 2021;53(3):874-880. Published online December 7, 2020; DOI: https://doi.org/10.4143/crt.2020.1066

Abstract PDF PubReader ePub

Purpose
The objective of this study was to describe and analyze the clinicopathological features of primary choriocarcinoma (PCC) observed in male patients treated at the Samsung Medical Center between 1996 and 2020.
Materials and Methods
We reviewed the clinical records of 14 male patients with PCC retrospectively to assess their demographic, histological, and clinical characteristics at the time of diagnosis as well as identify the treatment outcomes.
Results
The median age of the patients was 33 years. The primary tumor site was the testicles in seven cases (50%), the mediastinum in six cases (43%), and the brain in one case (7%). The most common metastatic site was the lungs (79%), followed by the brain (43%). All patients with PCC received cytotoxic chemotherapy. Twelve patients had records of their response to cytotoxic chemotherapy; of these 12 patients, eight (8/12, 67%) achieved an objective response, and four (4/12, 33%) achieved stable disease response as the best response during chemotherapy.
Conclusion
It is known that most male PCC patients eventually develop resistance to cytotoxic chemotherapy and die. Factors such as poor response to chemotherapy, high disease burden, brain metastasis, and hemoptysis at the time of diagnosis are associated with shorter survival time in male PCC patients. Programmed death-1/programmed death-ligand 1 blockade therapy can be a salvage treatment for chemotherapy-resistant male PCC patients.

Citations

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Pediatric primary extragonadal choriocarcinoma - A study on male patients at a single tertiary medical institution
Jui-Ju Tseng, Chi-Yen Chen, Chiung-Wen Liang, Fang-Liang Huang
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Frontiers in Immunology.2025;[Epub] CrossRef
Balloon-Release Pattern on the Chest X-ray of a Young Male Patient With Metastatic Testicular Choriocarcinoma: A Case Report of an Aggressive Pulmonary Presentation
Idalberto Luis Fernandez Eng, Yoniel Suarez-Guerrero, Eliany Leon Figueredo, Alicia de Fuenmayor Icardo, Idania Maria Cruzata Matos
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The tumor or inflammation? a case report on primary pulmonary choriocarcinoma
Na Wang, Nan Zhang, Xinyue Zhang, Yuanyuan Wang, Yajie Fu, Lingfei Guo, Changhu Liang, Mengru Yu
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Immunotherapy

The Pattern of Time to Onset and Resolution of Immune-Related Adverse Events Caused by Immune Checkpoint Inhibitors in Cancer: A Pooled Analysis of 23 Clinical Trials and 8,436 Patients: Si-Qi Tang, Ling-Long Tang, Yan-Ping Mao, Wen-Fei Li, Lei Chen, Yuan Zhang, Ying Guo, Qing Liu, Ying Sun, Cheng Xu, Jun Ma; Cancer Res Treat. 2021;53(2):339-354. Published online November 6, 2020; DOI: https://doi.org/10.4143/crt.2020.790

Abstract PDF Supplementary Material PubReader ePub

Purpose
The occurrence pattern of immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) in cancer treatment remains unclear.
Materials and Methods
Phase II-III clinical trials that evaluated ICI-based treatments in cancer and were published between January 2007 and December 2019 were retrieved from public electronic databases. The pooled median time to onset (PMT-O), resolution (PMT-R), and immune-modulation resolution (PMT-IMR) of irAEs were generated using the metamedian package of R software.
Results
Twenty-two eligible studies involving 23 clinical trials and 8,436 patients were included. The PMT-O of all-grade irAEs ranged from 2.2 to 14.8 weeks, with the longest in renal events. The PMT-O of grade ≥ 3 irAEs was significantly longer than that of all-grade irAEs induced by programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) inhibitors (27.5 weeks vs. 8.4 weeks, p < 0.001) and treatment of nivolumab (NIV) plus ipilimumab (IPI) (7.9 weeks vs. 6.0 weeks, p < 0.001). The PMT-R of all-grade irAEs ranged from 0.1 to 54.3 weeks, with the shortest and longest in hypersensitivity/infusion reaction and endocrine events, respectively. The PMT-IMR of grade ≥ 3 irAEs was significantly shorter than that of all-grade irAEs caused by PD-1/PD-L1 blockade (6.9 weeks vs. 40.6 weeks, p=0.002) and NIV+IPI treatment (3.1 weeks vs. 5.9 weeks, p=0.031).
Conclusion
This study revealed the general and specific occurrence pattern of ICI-induced irAEs in pan-cancers, which was deemed to aid the comprehensive understanding, timely detection, and effective management of ICI-induced irAEs.

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Lung cancer

Sequential Treatment with an Immune Checkpoint Inhibitor Followed by a Small-Molecule Targeted Agent Increases Drug-Induced Pneumonitis: Jongheon Jung, Hyae Young Kim, Dong-Gil Kim, Seog Yun Park, A Ra Ko, Ji-Youn Han, Heung Tae Kim, Jin Soo Lee, Youngjoo Lee; Cancer Res Treat. 2021;53(1):77-86. Published online August 6, 2020; DOI: https://doi.org/10.4143/crt.2020.543

Abstract PDF Supplementary Material PubReader ePub

Purpose
Immune checkpoint inhibitors (ICI) and targeted small-molecule drugs are mainstay elements of lung cancer chemotherapy. However, they are associated with development of pneumonitis, a rare, but potentially life-threatening event. We analyzed lung cancer patients treated with ICI to evaluate the effect of sequential therapeutic administration on the incidence of pneumonitis.
Materials and Methods
In this retrospective study, 242 patients were included. Serial radiologic findings taken during and immediately after ICI treatment were reviewed. Factors that increased pneumonitis and the relationship between peri-ICI chemotherapy and the development of pneumonitis were evaluated.
Results
Pneumonitis developed in 23 patients (9.5%); severe pneumonitis (grade ≥ 3) occurred in 13 of 23 patients (56%); pneumonitis-related death occurred in six. High-dose thoracic radiation (≥ 6,000 cGy) revealed a tendency toward high risk of pneumonitis (odds ratio, 2.642; 95% confidence interval, 0.932 to 7.490; p=0.068). Among 149 patients followed for ≥ 8 weeks after the final ICI dose, more patients who received targeted agents within 8-weeks post-ICI experienced pneumonitis (3/16, 18.8%) compared with patients who received cytotoxic agents (4/54, 7.4%) or no chemotherapy (4/79, 5.1%) (p=0.162). Targeted therapy was associated with earlier-onset pneumonitis than treatment with cytotoxic agents (35 vs. 62 days post-ICI, p=0.007); the resulting pneumonitis was more severe (grade ≥ 3, 100% vs. 0%, p=0.031).
Conclusion
Sequential administration of small-molecule targeted agents immediately after ICI may increase the risk of severe pneumonitis. The sequence of chemotherapy regimens that include ICI and targeted agents should be carefully planned to reduce the risk of pneumonitis in lung cancer patients.

Citations

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