Cancer Research and Treatment

Original Articles

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

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

421 View
35 Download

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; Received June 5, 2024 Accepted August 14, 2024 Published online August 16, 2024; DOI: https://doi.org/10.4143/crt.2024.531 [Epub ahead of print]

Abstract PDF PubReader ePub: 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.

513 View
82 Download

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.

819 View
90 Download

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.

1,702 View
136 Download

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

Abstract PDF Supplementary Material PubReader ePub

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.

Citations

Citations to this article as recorded by

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

5,418 View
205 Download
3 Web of Science
3 Crossref

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.

Citations

Citations to this article as recorded by

Tubulointerstitial nephritis antigen-like 1 from cancer-associated fibroblasts contribute to the progression of diffuse-type gastric cancers through the interaction with integrin β1
Dagyeong Lee, In-Hye Ham, Hye Jeong Oh, Dong Min Lee, Jung Hwan Yoon, Sang-Yong Son, Tae-Min Kim, Jae-Young Kim, Sang-Uk Han, Hoon Hur
Journal of Translational Medicine.2024;[Epub] CrossRef
Safety and Efficacy of Neoadjuvant Chemoimmunotherapy in Gastric Cancer Patients with a PD-L1 Positive Status: A Case Report
Alexandra V. Avgustinovich, Olga V. Bakina, Sergey G. Afanas’ev, Liudmila V. Spirina, Alexander M. Volkov
Current Issues in Molecular Biology.2023; 45(9): 7642. CrossRef
Targeting GAS6/AXL signaling improves the response to immunotherapy by restoring the anti-immunogenic tumor microenvironment in gastric cancer
Tae Hoon Kim, Dagyeong Lee, Hye Jeong Oh, In-Hye Ham, Dong Min Lee, Yulim Lee, Zhang Zhang, Ding Ke, Hoon Hur
Life Sciences.2023; 335: 122230. CrossRef

7,792 View
413 Download
5 Web of Science
3 Crossref

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.

Citations

Citations to this article as recorded by

The Relationship of PRAME Expression with Clinicopathologic Parameters and Immunologic Markers in Melanomas: In Silico Analysis
Yasemin Cakir, Banu Lebe
Applied Immunohistochemistry & Molecular Morphology.2025;[Epub] CrossRef
Biomarkers to predict efficacy of immune checkpoint inhibitors in colorectal cancer patients: a systematic review and meta-analysis
Hang Yu, Qingquan Liu, Keting Wu, Shuang Tang
Clinical and Experimental Medicine.2024;[Epub] CrossRef
An Insight into the Peculiarities of Signet-Ring Cell Carcinoma of the Colon – a Narrative Review
Loredana Farcaș, Diana Voskuil-Galoș
Journal of Medical and Radiation Oncology.2024; 4(7): 1. CrossRef
High serum IL-6 correlates with reduced clinical benefit of atezolizumab and bevacizumab in unresectable hepatocellular carcinoma
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
JHEP Reports.2023; 5(4): 100672. CrossRef
Identification of ZBTB4 as an immunological biomarker that can inhibit the proliferation and invasion of pancreatic cancer
Zhe Yang, Feiran Chen, Feng Wang, Xiubing Chen, Biaolin Zheng, Xiaomin Liao, Zhejun Deng, Xianxian Ruan, Jing Ning, Qing Li, Haixing Jiang, Shanyu Qin
BMC Cancer.2023;[Epub] CrossRef
PD-L1 Expression in Colorectal Carcinoma: A Comparison of 3 Scoring Methods in a Cohort of Jordanian Patients
Heyam A. Awad, Maher A. Sughayer, Jumana M. Obeid, Yaqoot N. Heilat, Ahmad S. Alhesa, Reda M. Yousef, Nabil M. Hasasna, Shafiq A. Masoud, Tareq Saleh
Applied Immunohistochemistry & Molecular Morphology.2023; 31(6): 379. CrossRef
Systemic Delivery of a STING Agonist‐Loaded Positively Charged Liposome Selectively Targets Tumor Immune Microenvironment and Suppresses Tumor Angiogenesis
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
Small.2023;[Epub] CrossRef
Review of the Immune Checkpoint Inhibitors in the Context of Cancer Treatment
Norah A. Alturki
Journal of Clinical Medicine.2023; 12(13): 4301. CrossRef
Enhancing head and neck tumor management with artificial intelligence: Integration and perspectives
Nian-Nian Zhong, Han-Qi Wang, Xin-Yue Huang, Zi-Zhan Li, Lei-Ming Cao, Fang-Yi Huo, Bing Liu, Lin-Lin Bu
Seminars in Cancer Biology.2023; 95: 52. CrossRef
Artificial intelligence for prediction of response to cancer immunotherapy
Yuhan Yang, Yunuo Zhao, Xici Liu, Juan Huang
Seminars in Cancer Biology.2022; 87: 137. CrossRef

6,218 View
259 Download
7 Web of Science
10 Crossref

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.

Citations

Citations to this article as recorded by

Immunotherapy plus chemotherapy in patients with advanced endometrial cancer: a cost-effectiveness analysis
Youwen Zhu, Kun Liu, Hong Zhu
Journal of Gynecologic Oncology.2025;[Epub] CrossRef
Cervical lymphoepithelioma-like carcinoma with deficient mismatch repair and loss of SMARCA4/BRG1: a case report and five related cases
Yu Miyama, Tomomi Kato, Masayasu Sato, Akira Yabuno, Kosei Hasegawa, Masanori Yasuda
Diagnostic Pathology.2024;[Epub] CrossRef
Prognostic factors of 87 ovarian yolk sac tumor (OYST) patients and molecular characteristics of persistent and recurrent OYST
Shanhui Liang, Huijuan Ge, Shuling Zhou, Jie Tang, Yanzi Gu, Xiaohua Wu, Jin Li
Gynecologic Oncology.2024; 187: 64. CrossRef
Immunotherapy in MMR-d/MSI-H recurrent/metastatic endometrial cancer
Renata Pacholczak-Madej, Michele Bartoletti, Lucia Musacchio, Mirosława Püsküllüoglu, Paweł Blecharz, Domenica Lorusso
Expert Review of Anticancer Therapy.2024; 24(8): 717. CrossRef
Expression patterns of mismatch repair proteins in cervical cancer uncover independent prognostic value of MSH-2
Madeleine Charlotte van den Berg, Hege F Berg, Tomasz Stokowy, Erling A Hoivik, Kathrine Woie, Hilde Engerud, Akinyemi I Ojesina, Ingfrid Salvesen Haldorsen, Jone Trovik, Bjørn I Bertelsen, Camilla Krakstad, Mari Kyllesø Halle, Janie Foote
International Journal of Gynecological Cancer.2024; 34(7): 993. CrossRef
Cervical cancer: a new era
Giuseppe Caruso, Matthew K Wagar, Heng-Cheng Hsu, Jorge Hoegl, Guido Martin Rey Valzacchi, Andreina Fernandes, Giuseppe Cucinella, Seda Sahin Aker, Aarthi S Jayraj, Jessica Mauro, Rene Pareja, Pedro T Ramirez
International Journal of Gynecological Cancer.2024; 34(12): 1946. CrossRef
Unraveling the Heterogeneity of Deficiency of Mismatch Repair Proteins in Endometrial Cancer: Predictive Biomarkers and Assessment Challenges
Filomena M. Carvalho, Jesus P. Carvalho
Cancers.2024; 16(20): 3452. CrossRef
Long-term benefit of immunotherapy in a patient with squamous lung cancer exhibiting mismatch repair deficient/high microsatellite instability/high tumor mutational burden: A case report and literature review
Na Li, Zixuan Wan, Dongyan Lu, Ruilian Chen, Xiaowei Ye
Frontiers in Immunology.2023;[Epub] CrossRef
Immune escape and resistance to immunotherapy in mismatch repair deficient tumors
Guillaume Mestrallet, Matthew Brown, Cansu Cimen Bozkus, Nina Bhardwaj
Frontiers in Immunology.2023;[Epub] CrossRef
Heterogeneous expression of mismatch repair proteins and interpretation of immunohistochemical results in colorectal cancer and endometrial cancer
Xiangzhao Li, Shifen Zhang, Jiamin Zeng, Sha-sha Song, Xiaoqing Liu, Wei Kang, Minyi Liang, Rui Yang, Hong Li, Li Liang
Pathology - Research and Practice.2023; 248: 154647. CrossRef
Rechallenge with Anti-PD-1 Inhibitors in Patients with Recurrent Gynecologic Malignancies
Migang Kim, Chi-Son Chang, Min Chul Choi, Jeong-Won Lee, Hyun Park, Won Duk Joo
Yonsei Medical Journal.2023; 64(10): 587. CrossRef
Successful neoadjuvant chemotherapy plus sintilimab for locally advanced cervical cancer: case series and review of the literature
Linlin Liu, Xianbo Deng, Shuang Guo, Shouhua Yang
Diagnostic Pathology.2023;[Epub] CrossRef
Adverse Effect of the Duration of Antibiotic Use Prior to Immune Checkpoint Inhibitors on the Overall Survival of Patients with Recurrent Gynecologic Malignancies
Hye-Ji Jung, Jong-Ho Park, Jina Oh, Sae-Mi Lee, Il-Yeo Jang, Jung-Yong Hong, Yoo-Young Lee, Hyun Jin Choi
Cancers.2023; 15(24): 5745. CrossRef
Uterine carcinosarcoma with microsatellite instability - does immunotherapy modify the therapeutic scenario? A case report and literature review
Diocesio Alves Pinto Andrade, Eduardo Paulino, Isabela Panzeri Carlotti Buzatto, Danilo Tadao Wada, Warne Pedro Andrade, Andreia Cristina Melo, Angelica Nogueira-Rodrigues
Brazilian Journal of Oncology.2023;[Epub] CrossRef
Immune checkpoint inhibitors in cervical cancer: Current status and research progress
Yunkai Xie, Weimin Kong, Xiaoling Zhao, He Zhang, Dan Luo, Shuning Chen
Frontiers in Oncology.2022;[Epub] CrossRef

6,893 View
293 Download
15 Web of Science
15 Crossref

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.

Citations

Citations to this article as recorded by

Progress of immune checkpoint inhibitors therapy for non-small cell lung cancer with liver metastases
Fan-jie Qu, Yi Zhou, Shuang Wu
British Journal of Cancer.2024; 130(2): 165. CrossRef
Effectiveness and Safety of Immune Checkpoint Inhibitors Alone or in Combination With Chemotherapy in Pulmonary Sarcomatoid Carcinoma
Daisuke Hazama, Kenji Nakahama, Hiroaki Kodama, Akito Miyazaki, Koichi Azuma, Yosuke Kawashima, Yuki Sato, Kentaro Ito, Yoshimasa Shiraishi, Keita Miura, Takayuki Takahama, Satoshi Oizumi, Yoshinobu Namba, Satoshi Ikeda, Hiroshige Yoshioka, Asuka Tsuya, Y
JTO Clinical and Research Reports.2024; 5(1): 100613. CrossRef
Evolving landscape of treatments targeting the microenvironment of liver metastases in non-small cell lung cancer
Lingling Zhu, Xianzhe Yu, Xiaojun Tang, Chenggong Hu, Lei Wu, Yanyang Liu, Qinghua Zhou
Chinese Medical Journal.2024; 137(9): 1019. CrossRef
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
Current Issues in Molecular Biology.2024; 46(12): 13443. CrossRef
Assessing the Relationship Between Liver Metastases and the Survival of Patients With Non-Small Cell Lung Cancer After Immune Checkpoint Inhibitors Treatment: A Systematic Review and Meta-Analysis
Huilin Xu, Pingpo Ming, Zhenyu Zhao, Nan Zhao, Dingjie Zhou, Xixian Tang, Dedong Cao
Integrative Cancer Therapies.2023;[Epub] CrossRef
Liver metastases and the efficacy of immune checkpoint inhibitors in advanced lung cancer: A systematic review and meta-analysis
Handai Xia, Wengang Zhang, Yuqing Zhang, Xiaoling Shang, Yanguo Liu, Xiuwen Wang
Frontiers in Oncology.2022;[Epub] CrossRef

7,756 View
254 Download
7 Web of Science
6 Crossref

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.

Citations

Citations to this article as recorded by

Immunomodulatory properties of HDAC6 inhibitors in cancer diseases: New chances for sophisticated drug design and treatment optimization
Bernhard Biersack, Bianca Nitzsche, Michael Höpfner
Seminars in Cell & Developmental Biology.2024; 154: 286. CrossRef
Regulation of PD-L1 Expression by YY1 in Cancer: Therapeutic Efficacy of Targeting YY1
Ana Dillen, Indy Bui, Megan Jung, Stephanie Agioti, Apostolos Zaravinos, Benjamin Bonavida
Cancers.2024; 16(6): 1237. CrossRef
Reducing PD-L1 Expression by Degraders and Downregulators as a Novel Strategy to Target the PD-1/PD-L1 Pathway
Zhijie Wang, Lin Yuan, Xiaotong Liao, Xia Guo, Jianjun Chen
Journal of Medicinal Chemistry.2024; 67(8): 6027. CrossRef
Dual molecule targeting HDAC6 leads to intratumoral CD4+ cytotoxic lymphocytes recruitment through MHC-II upregulation on lung cancer cells
Sarah Ducellier, Mélanie Demeules, Boris Letribot, Massimiliano Gaetani, Chloé Michaudel, Harry Sokol, Abdallah Hamze, Mouad Alami, Mégane Nascimento, Sébastien Apcher
Journal for ImmunoTherapy of Cancer.2024; 12(4): e007588. CrossRef
Selective HDAC6 Inhibition Has the Potential for Anti-Cancer Effect in Renal Cell Carcinoma
Tsutomu Anraku, Masaki Murata, Hiroo Kuroki, Akira Kazama, Yuko Shirono, Masayuki Tasaki, Vladimir Bilim, Yoshihiko Tomita
Journal of Personalized Medicine.2024; 14(7): 704. CrossRef
Histone deacetylase inhibitors for leukemia treatment: current status and future directions
Mohammad-Salar Hosseini, Zohreh Sanaat, Mohammad Amin Akbarzadeh, Yosra Vaez-Gharamaleki, Mahsa Akbarzadeh
European Journal of Medical Research.2024;[Epub] CrossRef
Epigenetic Modification of PD-1/PD-L1-Mediated Cancer Immunotherapy against Melanoma
Hikaru Nanamori, Yu Sawada
International Journal of Molecular Sciences.2022; 23(3): 1119. CrossRef
Epigenetic Alterations and Inflammation as Emerging Use for the Advancement of Treatment in Non-Small Cell Lung Cancer
Shuo Yang, Yang Huang, Qi Zhao
Frontiers in Immunology.2022;[Epub] CrossRef
Targeting HDAC6 to Overcome Autophagy-Promoted Anti-Cancer Drug Resistance
Hyein Jo, Kyeonghee Shim, Dooil Jeoung
International Journal of Molecular Sciences.2022; 23(17): 9592. CrossRef
Epigenetic modifications: Critical participants of the PD‑L1 regulatory mechanism in solid tumors (Review)
Xiaoran Ma, Jibiao Wu, Bin Wang, Cun Liu, Lijuan Liu, Changgang Sun
International Journal of Oncology.2022;[Epub] CrossRef

7,063 View
211 Download
10 Web of Science
10 Crossref

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.

Citations

Citations to this article as recorded by

A novel bispecific peptide targeting PD-1 and PD-L1 with combined antitumor activity of T-cells derived from the patients with TSCC
Lili Wang, Junheng Zheng, Zhihao Tan, Yan Zhang, Hua Wang
International Immunopharmacology.2024; 138: 112582. CrossRef
Peptide Blockers of PD-1-PD-L1 Interaction Reinvigorate PD-1-Suppressed T Cells and Curb Tumor Growth in Mice
Shanshan (Jenny) Zhong, Xiaoling Liu, Tomonori Kaneko, Yan Feng, Owen Hovey, Kyle Yang, Sally Ezra, Soon-Duck Ha, Sung Kim, John K. McCormick, Huadong Liu, Shawn Shun-Cheng Li
Cells.2024; 13(14): 1193. CrossRef
Melittin-incorporated nanomedicines for enhanced cancer immunotherapy
Xuefeng Duan, Haoyang Zou, Jiazhen Yang, Shixian Liu, Tianmin Xu, Jianxun Ding
Journal of Controlled Release.2024; 375: 285. CrossRef
Peptides as multifunctional players in cancer therapy
Sri Murugan Poongkavithai Vadevoo, Smriti Gurung, Hyun-Su Lee, Gowri Rangaswamy Gunassekaran, Seok-Min Lee, Jae-Won Yoon, Yun-Ki Lee, Byungheon Lee
Experimental & Molecular Medicine.2023; 55(6): 1099. CrossRef
Progress of research on PD-1/PD-L1 in leukemia
Huizhen Cao, Tianyu Wu, Xue Zhou, Shuyang Xie, Hongfang Sun, Yunxiao Sun, Youjie Li
Frontiers in Immunology.2023;[Epub] CrossRef
Development of PD-1 blockade peptide-cell conjugates to enhance cellular therapies for T-cell acute lymphoblastic leukemia
Quanxiao Wang, Hongxing Huang, Peisheng Liang, Lili Wang, Junheng Zheng, Yan Zhang, Hua Wang
Medical Oncology.2023;[Epub] CrossRef
Intratumoral immunotherapy using a TLR2/3 agonist, L-pampo, induces robust antitumor immune responses and enhances immune checkpoint blockade
Won Suk Lee, Dong Sung Kim, Jeong Hun Kim, Yoonki Heo, Hannah Yang, Eun-Jin Go, Jin Hyoung Kim, Seung Joon Lee, Byung Cheol Ahn, Jung Sun Yum, Hong Jae Chon, Chan Kim
Journal for ImmunoTherapy of Cancer.2022; 10(6): e004799. CrossRef

10,657 View
293 Download
8 Web of Science
7 Crossref

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

Citations to this article as recorded by

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
Exploring the ferroptosis-related gene lipocalin 2 as a potential biomarker for sepsis-induced acute respiratory distress syndrome based on machine learning
Jiayi Zhan, Junming Chen, Liyan Deng, Yining Lu, Lianxiang Luo
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2024; 1870(4): 167101. CrossRef
Evaluation of Blood Tumor Mutation Burden for the Efficacy of Second-Line Atezolizumab Treatment in Non-Small Cell Lung Cancer: BUDDY Trial
Cheol-Kyu Park, Ha Ra Jun, Hyung-Joo Oh, Ji-Young Lee, Hyun-Ju Cho, Young-Chul Kim, Jeong Eun Lee, Seong Hoon Yoon, Chang Min Choi, Jae Cheol Lee, Sung Yong Lee, Shin Yup Lee, Sung-Min Chun, In-Jae Oh
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
Frontiers in Immunology.2023;[Epub] CrossRef
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
BioMedInformatics.2023; 3(4): 1071. CrossRef
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

7,883 View
220 Download
12 Web of Science
6 Crossref

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

Citations to this article as recorded by

Primary retroperitoneal choriocarcinoma with lung and liver metastasis in a male patient: case report
Guimei Wang, Ronghui Li
Oncologie.2024; 26(1): 167. CrossRef
A poor prognostic male choriocarcinoma with multiple systemic metastases: a case report and the literature review
Wenpeng Huang, Zuohuan Zheng, Zheng Bao, Xiaoyan Xiao, Liming Li, Zhaonan Sun, Lei Kang
Frontiers in Medicine.2024;[Epub] CrossRef
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
Pediatrics & Neonatology.2024;[Epub] CrossRef
Comparative analysis of testicular and nontesticular choriocarcinoma: a population-based study
Sakhr Alshwayyat, Maen S. Soudi, Marwa T. Qaddoura, Tala A. Alshwayyat, Obada Ababneh, Hamdah Hanifa, Ramez M. Odat, Rami S. AlAzab
Annals of Medicine & Surgery.2024; 86(12): 6951. CrossRef
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
Frontiers in Oncology.2023;[Epub] CrossRef
Pure testicular choriocarcinoma, a rare and highly malignant subtype with challenging treatment: A case report and review of the literature
Na Lei, Li-Li Lei, Chao-Hong Wang, Chao-Rong Mei
Molecular and Clinical Oncology.2023;[Epub] CrossRef
Antineoplastics

Reactions Weekly.2022; 1890(1): 41. CrossRef
Case Report: Treatment of primary pulmonary choriocarcinoma with lung lobectomy and adjuvant chemotherapy
Andrea M. Johnson, Christiana M. Johnson, Zena Khalil, Maria Stitzel, Deanna Teoh
Gynecologic Oncology Reports.2022; 43: 101064. CrossRef
Extragonadal Germ Cell Tumors of the Mediastinum and Retroperitoneum
David Aguiar Bujanda, Daniel Pérez Cabrera, Laura Croissier Sánchez
American Journal of Clinical Oncology.2022; 45(12): 493. CrossRef

7,052 View
155 Download
10 Web of Science
9 Crossref

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.

Citations

Citations to this article as recorded by

Association between immune checkpoint inhibitor and cytomegalovirus infection: A pharmacovigilance study based on the adverse event reporting system
Naoto Okada, Tomoyuki Yanagi, Takaaki Sasaki, Miho Tamura, Masakazu Ozaki, Atsuyuki Saisyo, Takashi Kitahara
International Journal of Cancer.2025; 156(2): 293. CrossRef
A Case of Olmesartan-associated Gastritis Observed Over Time
Mizuho Fujisawa, Tetsuya Yoshizaki, Satoshi Urakami, Risa Ashizaki, Eri Nishikawa, Hiroshi Tanabe, Shinya Hoki, Ryosuke Ishida, Hitomi Hori, Chise Ueda, Hirofumi Abe, Madoka Takao, Yoshinori Morita, Takashi Toyonaga, Yuzo Kodama
Internal Medicine.2025;[Epub] CrossRef
The use of peripheral blood biomarkers for predicting the risk of immune-related adverse events in immune checkpoint inhibitor therapy
Louise E Duvall
Annals of Clinical Biochemistry: International Journal of Laboratory Medicine.2025;[Epub] CrossRef
Developing alert thresholds and self-management advice for people receiving immune checkpoint inhibitors: a Multinational Association for Supportive Care in Cancer modified Delphi survey
Julia Lai-Kwon, Claudia Rutherford, Stephanie Best, Hope S. Rugo, Christina H. Ruhlmann, Michael Jefford
Supportive Care in Cancer.2025;[Epub] CrossRef
Immune checkpoint inhibitor–related adverse events: Real-world experience from a single veterans’ affairs medical center
Samantha Benz, Katherine A Sherman, Constantin A Dasanu, Juliana Alvarez-Argote
Journal of Oncology Pharmacy Practice.2024; 30(4): 697. CrossRef
Assessment of Variables Related to the Risk of Severe Adverse Events in Cutaneous Melanoma Patients Treated with Immune Checkpoint Inhibitors
Kremena Petrova Trichkova, Franziska Görtler, Line Bjørge, Cornelia Schuster
Cancers.2024; 16(2): 250. CrossRef
Management of liver and gastrointestinal toxicity induced by immune checkpoint inhibitors: Position statement of the AEEH–AEG–SEPD–SEOM–GETECCU
Mar Riveiro-Barciela, Sabela Carballal, Álvaro Díaz-González, Míriam Mañosa, Javier Gallego-Plazas, Joaquín Cubiella, Paula Jiménez-Fonseca, María Varela, Luis Menchén, Bruno Sangro, Ana Fernández-Montes, Francisco Mesonero, Miguel Ángel Rodríguez-Gandía,
Gastroenterología y Hepatología.2024; 47(4): 401. CrossRef
Management of liver and gastrointestinal toxicity induced by immune checkpoint inhibitors: Position statement of the AEEH-AEG-SEPD-SEOM-GETECCU
Mar Riveiro-Barciela, Sabela carballal, Álvaro Díaz-González, Miriam Mañosa, Javier Gallgo-Plazas, Joaquín Cubiella, Paula Jiménez-Fonseca, María Varela, Luis Menchén, Bruno Sangro, Ana Fernández-Montes, Francisco Mesonero, Miguel Ángel Rodríguez-Gandí
Revista Española de Enfermedades Digestivas.2024;[Epub] CrossRef
Discontinuation risk from adverse events: immunotherapy alone vs. combined with chemotherapy: a systematic review and network meta-analysis
Sangwon Shin, Jimin Moon, Chiyoon Oum, Seulki Kim, Soo Ick Cho, Yoojoo Lim, Chan-Young Ock, Seunghwan Shin
BMC Cancer.2024;[Epub] CrossRef
A case of Stiff-person syndrome with muscle tonicity of the extremities and neck after use of Dulvalumab for lung adenocarcinoma
Takashi Inoue, Kei Oiwa, Kazuhiro Horiuchi
Rinsho Shinkeigaku.2024; 64(3): 176. CrossRef
Clinical and translational attributes of immune-related adverse events
Karijn P. M. Suijkerbuijk, Mick J. M. van Eijs, Femke van Wijk, Alexander M. M. Eggermont
Nature Cancer.2024; 5(4): 557. CrossRef
Immune checkpoint inhibitors and neurotoxicity: a focus on diagnosis and management for a multidisciplinary approach
Desirèe Speranza, Mariacarmela Santarpia, Francesco Luppino, Fausto Omero, Enrica Maiorana, Mariacarmela Cavaleri, Elena Sapuppo, Vincenzo Cianci, Alessia Pugliese, Vito Racanelli, Giulia Maria Camerino, Carmelo Rodolico, Nicola Silvestris
Expert Opinion on Drug Safety.2024; 23(11): 1405. CrossRef
Immune-Related Colitis Is Associated with Fecal Microbial Dysbiosis and Can Be Mitigated by Fecal Microbiota Transplantation
Arielle Elkrief, Nicholas R. Waters, Natalie Smith, Angel Dai, John Slingerland, Nathan Aleynick, Binita Febles, Pooja Gogia, Nicholas D. Socci, Melissa Lumish, Paul A. Giardina, Jamie E. Chaft, Juliana Eng, Robert J. Motzer, Robin B. Mendelsohn, Kate A.
Cancer Immunology Research.2024; 12(3): 308. CrossRef
Management of liver and gastrointestinal toxicity induced by immune checkpoint inhibitors: Position statement of the AEEH–AEG–SEPD–SEOM–GETECCU
Mar Riveiro-Barciela, Sabela Carballal, Álvaro Díaz-González, Míriam Mañosa, Javier Gallego-Plazas, Joaquín Cubiella, Paula Jiménez-Fonseca, María Varela, Luis Menchén, Bruno Sangro, Ana Fernández-Montes, Francisco Mesonero, Miguel Ángel Rodríguez-Gandía,
Gastroenterología y Hepatología (English Edition).2024; 47(4): 401. CrossRef
Pathogenesis, Diagnosis and Treatment of Immune-Related Cardiotoxicity
静宜任
Advances in Clinical Medicine.2024; 14(03): 284. CrossRef
Extending the dosing intervals of nivolumab: model-based simulations in unselected cancer patients
Alicja Puszkiel, Guillaume Bianconi, Blaise Pasquiers, David Balakirouchenane, Jennifer Arrondeau, Pascaline Boudou-Rouquette, Marie-Claire Bretagne, Joe-Elie Salem, Xavier Declèves, Michel Vidal, Nora Kramkimel, Sarah Guegan, Selim Aractingi, Olivier Hui
British Journal of Cancer.2024; 130(11): 1866. CrossRef
Endocrine-metabolic assessment checklist for cancer patients treated with immunotherapy: A proposal by the Italian Association of Medical Oncology (AIOM), Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian S
Maria Chiara Zatelli, Antongiulio Faggiano, Antonella Argentiero, Romano Danesi, Stella D'Oronzo, Stefano Fogli, Tindara Franchina, Francesco Giorgino, Nicola Marrano, Dario Giuffrida, Stefania Gori, Giampiero Marino, Rossella Mazzilli, Matteo Monami, Mon
Cancer Treatment Reviews.2024; 126: 102734. CrossRef
Guide for the Diagnosis of Immune Checkpoint Inhibitor-Induced Liver Injury
Takanori Ito, Yasuto Takeuchi, Kazuyuki Mizuno, Michitaka Imai, Yoko Yoshimaru, Kazumichi Abe, Masanori Abe, Takanori Matsuura, Masataka Yokode, Masahiro Shiokawa, Yuzo Kodama, Mina Komuta, Kenichi Harada, Atsushi Tanaka
Kanzo.2024; 65(6): 268. CrossRef
Diagnostic guide for immune checkpoint inhibitor‐induced liver injury
Takanori Ito, Yasuto Takeuchi, Kazuyuki Mizuno, Michitaka Imai, Yoko Yoshimaru, Kazumichi Abe, Masanori Abe, Takanori Matsuura, Masataka Yokode, Masahiro Shiokawa, Yuzo Kodama, Mina Komuta, Kenichi Harada, Atsushi Tanaka
Hepatology Research.2024; 54(8): 719. CrossRef
Oral and cutaneous immune‐related adverse events in cancer patients: Prevalence and overall survival
Osias Vieira de Oliveira Filho, Ivana Lameiras Gibbons, Yuri de Lima Medeiros, Thiago Bueno de Oliveira, Nathaniel Simon Treister, Fabio Abreu Alves
Oral Diseases.2024;[Epub] CrossRef
Tumor-Agnostic Therapy—The Final Step Forward in the Cure for Human Neoplasms?
Mohamed Mahmoud El-Sayed, Julia Raffaella Bianco, YiJing Li, Zsolt Fabian
Cells.2024; 13(12): 1071. CrossRef
Mesenteric Panniculitis as a Side Effect of Nivolumab in a Patient with Larnyngeal Cancer
O Karhan, Y Sezgin, S Ileri, S Tunc
Nigerian Journal of Clinical Practice.2024; 27(6): 800. CrossRef
Real‐world first‐line treatment with pembrolizumab for non‐small cell lung carcinoma with high PD‐L1 expression: Updated analysis
Yasuyuki Ikezawa, Ryo Morita, Hidenori Mizugaki, Kazunari Tateishi, Keiki Yokoo, Toshiyuki Sumi, Hajime Kikuchi, Yasuo Kitamura, Atsushi Nakamura, Maki Kobayashi, Mari Aso, Nozomu Kimura, Fumiaki Yoshiike, Furuta Megumi, Hisashi Tanaka, Motoki Sekikawa, T
Cancer Medicine.2024;[Epub] CrossRef
Multi-organ immune-related adverse events from immune checkpoint inhibitors and their downstream implications: a retrospective multicohort study
Guihong Wan, Wenxin Chen, Sara Khattab, Katie Roster, Nga Nguyen, Boshen Yan, Ahmad Rajeh, Jayhyun Seo, Hannah Rashdan, Leyre Zubiri, Matthew J Hadfield, Shadmehr Demehri, Kun-Hsing Yu, William Lotter, Alexander Gusev, Nicole R LeBoeuf, Kerry L Reynolds,
The Lancet Oncology.2024; 25(8): 1053. CrossRef
Selecting Immune Checkpoint Inhibitor Side Effects for Real-Time Monitoring in Routine Cancer Care: A Modified Delphi Study
Julia Lai-Kwon, Michael Jefford, Stephanie Best, Iris Zhang, Claudia Rutherford
JCO Oncology Practice.2024; 20(12): 1663. CrossRef
Differences in checkpoint-inhibitor-induced hypophysitis: mono- versus combination therapy induced hypophysitis
Stephanie van der Leij, Karijn P.M. Suijkerbuijk, Medard F.M. van den Broek, Gerlof D. Valk, Jan Willem Dankbaar, Hanneke M. van Santen
Frontiers in Endocrinology.2024;[Epub] CrossRef
Unravelling the Acute, Chronic and Steroid-Refractory Management of High-Grade Neurological Immune-Related Adverse Events: A Call to Action
Antonio Malvaso, Pierpaolo Giglio, Luca Diamanti, Matteo Gastaldi, Elisa Vegezzi, Andrea Pace, Paola Bini, Enrico Marchioni
Brain Sciences.2024; 14(8): 764. CrossRef
Machine learning modeling of patient health signals informs long-term survival on immune checkpoint inhibitor therapy
Gerald J. Sun, Gustavo Arango-Argoty, Gary J. Doherty, Damian E. Bikiel, Dejan Pavlovic, Allen C. Chen, Ross A. Stewart, Zhongwu Lai, Etai Jacob
iScience.2024; 27(9): 110634. CrossRef
Clinical Outcomes of Elective Early Discontinuation of Immunotherapy Based on Objective Response in Microsatellite Instability-High Metastatic Colorectal Cancer
Annie Xiao, Xiaochen Li, Chongkai Wang, Marwan Fakih
Clinical Colorectal Cancer.2024;[Epub] CrossRef
Toxicity in the era of immune checkpoint inhibitor therapy
Synat Keam, Naimah Turner, Fernanda G. Kugeratski, Rene Rico, Jocelynn Colunga-Minutti, Rayansh Poojary, Sayan Alekseev, Anisha B. Patel, Yuanteng Jeff Li, Ajay Sheshadri, Monica E. Loghin, Karin Woodman, Ashley E. Aaroe, Sarah Hamidi, Priyanka Chandrasek
Frontiers in Immunology.2024;[Epub] CrossRef
Onco-Primary Care of Patients Receiving Immune Checkpoint Inhibitors
Christopher J. Hoimes, Suzanne McGettigan, Lee Schwartzberg
The American Journal of Medicine.2024; 137(12): 1200. CrossRef
Subjective symptoms are triggers for the detection of immune checkpoint inhibitor-induced interstitial lung disease and associate with disease severity: a single-center retrospective study
Mari Yokoi, Atsushi Yonezawa, Daiki Hira, Tomohiro Handa, Kiminobu Tanizawa, Shunsaku Nakagawa, Masahiro Tsuda, Yasuaki Ikemi, Ryo Itotani, Hironori Yoshida, Motoo Nomura, Junichi Matsubara, Kosaku Murakami, Hiroaki Ozasa, Manabu Muto, Tomohiro Terada
Journal of Pharmaceutical Health Care and Sciences.2024;[Epub] CrossRef
Melittin-incorporated nanomedicines for enhanced cancer immunotherapy
Xuefeng Duan, Haoyang Zou, Jiazhen Yang, Shixian Liu, Tianmin Xu, Jianxun Ding
Journal of Controlled Release.2024; 375: 285. CrossRef
Do corticosteroids affect immunotherapy efficacy in malignancy? – A systematic review
Yoni Byron, Sonya Yegorova‐Lee, Martin Tio
Cancer Medicine.2024;[Epub] CrossRef
Immune Checkpoint Inhibitors in the Pre-Transplant Hepatocellular Carcinoma Setting: A Glimpse Beyond the Liver
Luca Marzi, Andrea Mega, Chiara Turri, Stefano Gitto, Federica Ferro, Gilbert Spizzo
International Journal of Molecular Sciences.2024; 25(21): 11676. CrossRef
Assessing the Prognostic Value of Cytoplasmic and Stromal Caveolin-1 in Early Triple-Negative Breast Cancer Undergoing Neoadjuvant Chemotherapy
Iris Teruel, Eva Castellà, Sabela Recalde, Gemma Viñas, Anna Petit, Macedonia Trigueros, Eva Martínez-Balibrea, Eudald Felip, Milana Bergamino, Adrià Bernat-Peguera, Beatriz Cirauqui, Vanesa Quiroga, Angelica Ferrando-Díez, Anna Pous, Assumpció López, Lai
International Journal of Molecular Sciences.2024; 25(22): 12241. CrossRef
Real world comparison of immune-related adverse events with nivolumab-relatlimab versus ipilimumab-nivolumab in patients with advanced cutaneous melanoma
Brooke Kielkowski, Diana Mansour, Brooke Ebbert, Kelsea Seago, Sijin Wen, Hang Li, Christine Barrett
Journal of Oncology Pharmacy Practice.2024;[Epub] CrossRef
Association of Immune-Related Adverse Events With Efficacy in Consolidation Nivolumab Plus Ipilimumab or Nivolumab Alone After Chemoradiation in Patients With Unresectable Stage III Nonsmall Cell Lung Cancer: An Exploratory Analysis From the Big 10 Cancer
Cynthia X. Wei, Sandra K. Althouse, Hirva Mamdani, Nasser H. Hanna, Greg A. Durm
Clinical Lung Cancer.2024;[Epub] CrossRef
Safety of sequential immune checkpoint inhibitors after prior immune therapy
Muhammad Awidi, Brendan Connell, Delaney Johnson, Isabel Craven, Rojer Ranjit, Brigitte Gil, Natalie Dal’Bo, Lewena Maher, Seanna Reilly Daves, Stephanie McDonald, Krishna S. Gunturu
Journal of Cancer Research and Clinical Oncology.2023; 149(6): 2375. CrossRef
The role of immune checkpoint inhibitors in clinical practice: an analysis of the treatment patterns, survival and toxicity rates by sex
Murielle N. Wahli, Stefanie Hayoz, Dennis Hoch, Christoph O. Ryser, Michèle Hoffmann, Amina Scherz, Birgit Schwacha-Eipper, Simon Häfliger, Julian Wampfler, Martin D. Berger, Urban Novak, Berna C. Özdemir
Journal of Cancer Research and Clinical Oncology.2023; 149(7): 3847. CrossRef
Association between skin immune-related adverse events (irAEs) and multisystem irAEs during PD-1/PD-L1 inhibitor monotherapy
Atsushi Yamaguchi, Yoshitaka Saito, Katsuya Narumi, Ayako Furugen, Yoh Takekuma, Naofumi Shinagawa, Yasushi Shimizu, Hirotoshi Dosaka-Akita, Mitsuru Sugawara, Masaki Kobayashi
Journal of Cancer Research and Clinical Oncology.2023; 149(4): 1659. CrossRef
Immune checkpoint inhibitor-induced pure red cell aplasia: Case series and large‐scale pharmacovigilance analysis
Qian Guo, Jian Gao, Hui Guo, Jun Xie, Jingmin Cheng
International Immunopharmacology.2023; 114: 109490. CrossRef
Prognostic Significance of the Severity of Immune-Related Adverse Events in Advanced Cancer Patients Treated with PD-1/PD-L1 Inhibitors: A Real-World Data Analysis
Su Jeong Song, Yun-Kyoung Song, Mihwa Jang, Eunjeong Shin, Sung Yun Suh, Yoon Sook Cho, Ju-Yeun Lee, Jung Mi Oh
Targeted Oncology.2023; 18(1): 147. CrossRef
Immune checkpoint inhibitor-induced aplastic anaemia: Case series and large-scale pharmacovigilance analysis
Qian Guo, Jin Ning Zhao, Ting Liu, Jian Gao, Hui Guo, Jing Min Cheng
Frontiers in Pharmacology.2023;[Epub] CrossRef
Association of Immune-Related Adverse Events With Efficacy of Atezolizumab in Patients With Non–Small Cell Lung Cancer
Mark A. Socinski, Robert M. Jotte, Federico Cappuzzo, Makoto Nishio, Tony S. K. Mok, Martin Reck, Gene G. Finley, Monika D. Kaul, Wei Yu, Nindhana Paranthaman, Ilze Bāra, Howard J. West
JAMA Oncology.2023; 9(4): 527. CrossRef
Management of Non-Melanoma Skin Cancer: Radiologists Challenging and Risk Assessment
Gaetano Maria Russo, Anna Russo, Fabrizio Urraro, Fabrizio Cioce, Luigi Gallo, Maria Paola Belfiore, Angelo Sangiovanni, Stefania Napolitano, Teresa Troiani, Pasquale Verolino, Antonello Sica, Gabriella Brancaccio, Giulia Briatico, Valerio Nardone, Alfons
Diagnostics.2023; 13(4): 793. CrossRef
Blood cell counts can predict adverse events of immune checkpoint inhibitors: A systematic review and meta-analysis
Juyue Zhou, Zhonghai Du, Jie Fu, Xiuxiu Yi
Frontiers in Immunology.2023;[Epub] CrossRef
Gastritis as an immunotherapy-related toxicity in the treatment of endometrial cancer: A case report
Nidhi Goel, Monica D. Levine, Laura M. Chambers, Christa I. Nagel
Gynecologic Oncology Reports.2023; 47: 101174. CrossRef
Society for Immunotherapy of Cancer (SITC) consensus definitions for immune checkpoint inhibitor-associated immune-related adverse events (irAEs) terminology
Jarushka Naidoo, Catherine Murphy, Michael B Atkins, Julie R Brahmer, Stephane Champiat, David Feltquate, Lee M Krug, Javid Moslehi, M Catherine Pietanza, Joanne Riemer, Caroline Robert, Elad Sharon, Maria E Suarez-Almazor, Karthik Suresh, Michelle Turner
Journal for ImmunoTherapy of Cancer.2023; 11(3): e006398. CrossRef
Multidisciplinary recommendations for essential baseline functional and laboratory tests to facilitate early diagnosis and management of immune-related adverse events among cancer patients
Berna C. Özdemir, Cristina Espinosa da Silva, Dimitri Arangalage, Pierre Monney, Sabina A. Guler, Uyen Huynh-Do, Guido Stirnimann, Lucia Possamai, Roman Trepp, Robert Hoepner, Anke Salmen, Camille L. Gerard, Petr Hruz, Lisa Christ, Sacha I. Rothschild
Cancer Immunology, Immunotherapy.2023; 72(7): 1991. CrossRef
Immune checkpoint inhibitor-induced cutaneous toxicities: a review of histopathologic and clinical features
Julianna Martel, Hannah L. Hanania, Anisha B. Patel
Human Pathology.2023; 140: 144. CrossRef
Immune checkpoint inhibitors: maximizing benefit whilst minimizing toxicity
Catherine C. Fahey, Thomas J. Gracie, Douglas B. Johnson
Expert Review of Anticancer Therapy.2023; 23(7): 673. CrossRef
Prevalence of immune-related adverse events and anti-tumor efficacy in advanced/metastatic urothelial carcinoma following immune-checkpoint inhibitor treatment
Rafael Morales-Barrera, Guillermo Villacampa, Natalia Vidal, Mariona Figols, Julia Giner, Teresa Bonfill, Cristina Suárez, Nely Díaz, Joaquín Mateo, Macarena González, Montserrat Domenech, Javier Puente, Joan Carles
Clinical and Translational Oncology.2023; 25(12): 3556. CrossRef
The Feasibility, Acceptability, and Effectiveness of Electronic Patient-Reported Outcome Symptom Monitoring for Immune Checkpoint Inhibitor Toxicities: A Systematic Review
Julia Lai-Kwon, Jordan E. Cohen, Karolina Lisy, Claudia Rutherford, Afaf Girgis, Ethan Basch, Michael Jefford
JCO Clinical Cancer Informatics.2023;[Epub] CrossRef
Elevated eosinophils proportion as predictor of immune‐related adverse events after ipilimumab and nivolumab treatment of advanced and metastatic renal cell carcinoma
Yoshihiko Tasaki, Shuzo Hamamoto, Yosuke Sugiyama, Nami Tomiyama, Taku Naiki, Toshiki Etani, Kazumi Taguchi, Nayuka Matsuyama, Yasuhito Sue, Yoshihisa Mimura, Hiroki Kubota, Yusuke Noda, Maria Aoki, Yoshinobu Moritoki, Satoshi Nozaki, Satoshi Kurokawa, At
International Journal of Urology.2023; 30(10): 866. CrossRef
Antinuclear antibody (ANA) status predicts immune-related adverse events in liver cancer patients undergoing anti-PD-1 therapy
Shu-Jung Hsu, Yen-Cheng Chao, Xia-Hui Lin, Hua-Hua Liu, Yang Zhang, Wei-Feng Hong, Mao-Pei Chen, Xin Xu, Lan Zhang, Zheng-Gang Ren, Shi-Suo Du, Rong-Xin Chen
Clinical and Experimental Immunology.2023; 212(3): 239. CrossRef
First-Line, Fixed-Duration Nivolumab Plus Ipilimumab Followed by Nivolumab in Clinically Diverse Patient Populations With Unresectable Stage III or IV Melanoma: CheckMate 401
Reinhard Dummer, Pippa Corrie, Ralf Gutzmer, Tarek M. Meniawy, Michele Del Vecchio, Céleste Lebbé, Michele Guida, Caroline Dutriaux, Brigitte Dreno, Nicolas Meyer, Pier Francesco Ferrucci, Stéphane Dalle, Muhammad Adnan Khattak, Jean-Jacques Grob, Karen B
Journal of Clinical Oncology.2023; 41(23): 3917. CrossRef
Early-Stage Triple-Negative Breast Cancer Journey: Beginning, End, and Everything in Between
Hyo Sook Han, Praveen Vikas, Ricardo L.B. Costa, Nusrat Jahan, Ammanuel Taye, Erica M. Stringer-Reasor
American Society of Clinical Oncology Educational Book.2023;[Epub] CrossRef
An updated review of gastrointestinal toxicity induced by PD-1 inhibitors: from mechanisms to management
Yiyu Cheng, Fangmei Ling, Junrong Li, Yidong Chen, Mingyang Xu, Shuang Li, Liangru Zhu
Frontiers in Immunology.2023;[Epub] CrossRef
Postmarketing surveillance of nivolumab plus ipilimumab combination therapy in Japanese patients with unresectable malignant melanoma
Naoya Yamazaki, Yoshio Kiyohara, Hisashi Uhara, Tetsuya Tsuchida, Ai Yoshida, Takako Yamada, Akira Komoto
The Journal of Dermatology.2023; 50(9): 1108. CrossRef
Real‐world evidence of incidence and outcomes of aplastic anaemia following administration of immune checkpoint inhibitors
Srilatha Dasari, William Tse, Jiasheng Wang
British Journal of Haematology.2023; 202(6): 1205. CrossRef
Development of an eHealth-enhanced model of care for the monitoring and management of immune-related adverse events in patients treated with immune checkpoint inhibitors
André Manuel da Silva Lopes, Sara Colomer-Lahiguera, Célia Darnac, Stellio Giacomini, Sébastien Bugeia, Garance Gutknecht, Gilliosa Spurrier-Bernard, Veronica Aedo-Lopez, Nuria Mederos, Sofiya Latifyan, Alfredo Addedo, Olivier Michielin, Manuela Eicher
Supportive Care in Cancer.2023;[Epub] CrossRef
CD4 T cells and toxicity from immune checkpoint blockade
Noah Earland, Wubing Zhang, Abul Usmani, Aishwarya Nene, Antonella Bacchiocchi, David Y. Chen, Mario Sznol, Ruth Halaban, Aadel A. Chaudhuri, Aaron M. Newman
Immunological Reviews.2023; 318(1): 96. CrossRef
Anti‑PD1 therapy‑associated distal renal tubular acidosis: A case report
Xuejia Qiu, Bingnan Ren, Lingzhi Fang, Zhanjun Dong
Experimental and Therapeutic Medicine.2023;[Epub] CrossRef
Recent advances in immune checkpoint inhibitors in the treatment of urothelial carcinoma: A review
Minoru Kato, Junji Uchida
International Journal of Urology.2023; 30(12): 1068. CrossRef
Severe Immune-Related Enteritis after In Utero Exposure to Pembrolizumab
Manuel A. Baarslag, Joosje H. Heimovaara, Jessica S.W. Borgers, Koen J. van Aerde, Hans J.P.M. Koenen, Ruben L. Smeets, Pauline L.M. Buitelaar, Dick Pluim, Shoko Vos, Stefanie S.V. Henriet, Jan Willem B. de Groot, Martine van Grotel, Hilde Rosing, Jos H.
New England Journal of Medicine.2023; 389(19): 1790. CrossRef
Incidence and Timing of Immune-Related Adverse Events in Immune-Checkpoint Inhibitor-Treated Patients: A Retrospective Observational Study
Kou Masaki, Motoyasu Miyazaki, Hideki Kakimoto, Yuma Fukiage, Haruka Fukue, Akio Nakashima, Osamu Imakyure
Journal of Clinical Medicine.2023; 12(24): 7564. CrossRef
Immune checkpoint inhibitors and cancer immunotherapy by aptamers: an overview
Priyatharcini Kejamurthy, K. T. Ramya Devi
Medical Oncology.2023;[Epub] CrossRef
Imaging of Cancer Immunotherapy: Response Assessment Methods, Atypical Response Patterns, and Immune-Related Adverse Events, From theAJRSpecial Series on Imaging of Inflammation
Sara Sheikhbahaei, Charles V. Marcus, Mohammad S. Sadaghiani, Steven P. Rowe, Martin G. Pomper, Lilja B. Solnes
American Journal of Roentgenology.2022; 218(6): 940. CrossRef
Pharmacokinetic Simulation Analysis of Less Frequent Nivolumab and Pembrolizumab Dosing: Pharmacoeconomic Rationale for Dose Deescalation
Cody J. Peer, Brian L. Heiss, Daniel A. Goldstein, Jennifer C. Goodell, William D. Figg, Mark J. Ratain
The Journal of Clinical Pharmacology.2022; 62(4): 532. CrossRef
T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma
Alexander X. Lozano, Aadel A. Chaudhuri, Aishwarya Nene, Antonietta Bacchiocchi, Noah Earland, Matthew D. Vesely, Abul Usmani, Brandon E. Turner, Chloé B. Steen, Bogdan A. Luca, Ti Badri, Gunsagar S. Gulati, Milad R. Vahid, Farnaz Khameneh, Peter K. Harri
Nature Medicine.2022; 28(2): 353. CrossRef
Guarantee‐time bias in studies on the relationship between immune‐related adverse events and antitumor activity
Ka Man Cheung, Therese Yue Man Tsui, James Chung Hang Chow
Cancer.2022; 128(13): 2549. CrossRef
CD21lo B Cells Could Be a Potential Predictor of Immune-Related Adverse Events in Renal Cell Carcinoma
Kenichi Nishimura, Tatsuya Konishi, Toshiki Ochi, Ryuta Watanabe, Terutaka Noda, Tetsuya Fukumoto, Noriyoshi Miura, Yuki Miyauchi, Tadahiko Kikugawa, Katsuto Takenaka, Takashi Saika
Journal of Personalized Medicine.2022; 12(6): 888. CrossRef
A Phase I/IIa Randomized Trial Evaluating the Safety and Efficacy of SNK01 Plus Pembrolizumab in Patients with Stage IV Non-Small Cell Lung Cancer
Eo Jin Kim, Yong-Hee Cho, Dong Ha Kim, Dae-Hyun Ko, Eun-Ju Do, Sang-Yeob Kim, Yong Man Kim, Jae Seob Jung, Yoonmi Kang, Wonjun Ji, Myeong Geun Choi, Jae Cheol Lee, Jin Kyung Rho, Chang-Min Choi
Cancer Research and Treatment.2022; 54(4): 1005. CrossRef
Predictive Biomarkers of Severe Immune-Related Adverse Events With Immune Checkpoint Inhibitors: Prevention, Underlying Causes, Intensity, and Consequences
Ana Cardeña-Gutiérrez, Mónica López Barahona
Frontiers in Medicine.2022;[Epub] CrossRef
Human leucocyte antigen genotype association with the development of immune-related adverse events in patients with non-small cell lung cancer treated with single agent immunotherapy
Afaf Abed, Ngie Law, Leslie Calapre, Johnny Lo, Vikas Bhat, Samantha Bowyer, Michael Millward, Elin S. Gray
European Journal of Cancer.2022; 172: 98. CrossRef
Development of Lymphopenia during Therapy with Immune Checkpoint Inhibitors Is Associated with Poor Outcome in Metastatic Cutaneous Melanoma
Dirk Tomsitz, Max Schlaak, Sarah Zierold, Giulia Pesch, Thomas U. Schulz, Genoveva Müller, Christine Zecha, Lars E. French, Lucie Heinzerling
Cancers.2022; 14(13): 3282. CrossRef
Phase 1 Study of Chemoradiotherapy Combined with Nivolumab ± Ipilimumab for the Curative Treatment of Muscle-invasive Bladder Cancer
Ben-Max de Ruiter, Jons W. van Hattum, Djoeri Lipman, Theo M. de Reijke, R. Jeroen A. van Moorselaar, Erik J. van Gennep, A.H. Maartje Piet, Mila Donker, Tom van der Hulle, Jens Voortman, Jorg R. Oddens, Maarten C.C.M. Hulshof, Adriaan D. Bins
European Urology.2022; 82(5): 518. CrossRef
Adverse Renal Effects of Anticancer Immunotherapy: A Review
Maciej Borówka, Stanisław Łącki-Zynzeling, Michał Nicze, Sylwia Kozak, Jerzy Chudek
Cancers.2022; 14(17): 4086. CrossRef
Evolution of Radiological Treatment Response Assessments for Cancer Immunotherapy: From iRECIST to Radiomics and Artificial Intelligence
Nari Kim, Eun Sung Lee, Sang Eun Won, Mihyun Yang, Amy Junghyun Lee, Youngbin Shin, Yousun Ko, Junhee Pyo, Hyo Jung Park, Kyung Won Kim
Korean Journal of Radiology.2022; 23(11): 1089. CrossRef
Use of PD-1 inhibitors in patients with end-stage renal disease: safety and clinical outcomes from real-world data
Jiasheng Wang, Srilatha Dasari, Dina Elantably, Akram Alkrekshi, Yeseong David Kim
Acta Oncologica.2022; 61(9): 1157. CrossRef
Association of High Levels of Antidrug Antibodies Against Atezolizumab With Clinical Outcomes and T-Cell Responses in Patients With Hepatocellular Carcinoma
Chan Kim, Hannah Yang, Ilhwan Kim, Beodeul Kang, Hyeyeong Kim, Hyunho Kim, Won Suk Lee, Sanghoon Jung, Ho Yeong Lim, Jaekyung Cheon, Hong Jae Chon
JAMA Oncology.2022; 8(12): 1825. CrossRef
Germline genetic variation and predicting immune checkpoint inhibitor induced toxicity
Ik Shin Chin, Aman Khan, Anna Olsson-Brown, Sophie Papa, Gary Middleton, Claire Palles
npj Genomic Medicine.2022;[Epub] CrossRef
The incidence and risk factors for acute kidney injury in patients treated with immune checkpoint inhibitors
Deniz Can Guven, Deniz Aral Ozbek, Taha Koray Sahin, Gozde Kavgaci, Melek Seren Aksun, Enes Erul, Hasan Cagri Yildirim, Elvin Chalabiyev, Cebrayil Cebroyilov, Tolga Yildirim, Omer Dizdar, Sercan Aksoy, Suayib Yalcin, Saadettin Kilickap, Mustafa Erman, Mus
Anti-Cancer Drugs.2022;[Epub] CrossRef
Vascular Normalization to Improve Treatment of COVID-19: Lessons from Treatment of Cancer
Lance L. Munn, Triantafyllos Stylianopoulos, Natalie K. Jain, C. Corey Hardin, Melin J. Khandekar, Rakesh K. Jain
Clinical Cancer Research.2021; 27(10): 2706. CrossRef
Lenvatinib plus pembrolizumab in patients with advanced or recurrent uterine carcinosarcoma
Jonathan T. Hunt, Laura M. Chambers, Meng Yao, Amy Joehlin-Price, Robert Debernardo, Peter G. Rose
Gynecologic Oncology Reports.2021; 37: 100840. CrossRef
Blocking antibody-mediated phosphatidylserine enhances cancer immunotherapy
Jie Zhang, Zhujiang Dai, Cheng Yan, Daorong Wang, Dong Tang
Journal of Cancer Research and Clinical Oncology.2021; 147(12): 3639. CrossRef
Important Surgical and Clinical End Points in Neoadjuvant Immunotherapy Trials in Resectable NSCLC
Jay M. Lee, Anthony W. Kim, Tomasz Marjanski, Pierre-Emmanuel Falcoz, Masahiro Tsuboi, Yi-Long Wu, Shawn W. Sun, Barbara J. Gitlitz
JTO Clinical and Research Reports.2021; 2(10): 100221. CrossRef
Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update
Bryan J. Schneider, Jarushka Naidoo, Bianca D. Santomasso, Christina Lacchetti, Sherry Adkins, Milan Anadkat, Michael B. Atkins, Kelly J. Brassil, Jeffrey M. Caterino, Ian Chau, Marianne J. Davies, Marc S. Ernstoff, Leslie Fecher, Monalisa Ghosh, Ishmael
Journal of Clinical Oncology.2021; 39(36): 4073. CrossRef
Rheumatic Manifestations and Diseases From Immune Checkpoint Inhibitors in Cancer Immunotherapy
Pan Shen, Xuan Deng, Zhishuo Hu, Zhe Chen, Yao Huang, Ke Wang, Kai Qin, Ying Huang, Xin Ba, Jiahui Yan, Liang Han, Shenghao Tu
Frontiers in Medicine.2021;[Epub] CrossRef

14,526 View
691 Download
85 Web of Science
90 Crossref

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

Citations to this article as recorded by

Toxicities associated with sequential or combined use of immune checkpoint inhibitors and small targeted therapies in non-small cell lung cancer: A critical review of the literature
Anne-Laure Désage, Michael Duruisseaux, Claire Lafitte, Sophie Bayle-Bleuez, Christos Chouaid, Pierre Fournel, Thomas Pierret
Cancer Treatment Reviews.2024; 129: 102805. CrossRef
Deep learning for predicting the risk of immune checkpoint inhibitor-related pneumonitis in lung cancer
M. Cheng, R. Lin, N. Bai, Y. Zhang, H. Wang, M. Guo, X. Duan, J. Zheng, Z. Qiu, Y. Zhao
Clinical Radiology.2023; 78(5): e377. CrossRef
Evaluating Pneumonitis Incidence in Patients with Non–small Cell Lung Cancer Treated with Immunotherapy and/or Chemotherapy Using Real-world and Clinical Trial Data
Qi Liu, Chenan Zhang, Yue Huang, Ruihao Huang, Shiew-Mei Huang, Erin Larkins, Liza Stapleford, Donna R. Rivera, Paul G. Kluetz, Shenggang Wang, Hao Zhu, James Weese, Elizabeth Cromartie, Mahder Teka, Sheetal Walters, Frank Wolf, Thomas D. Brown
Cancer Research Communications.2023; 3(2): 258. CrossRef
Pulmonary toxicity in driver gene positive non-small cell lung cancer therapy
Yi-Pu Zhao, Yong Long
Current Medical Research and Opinion.2022; 38(8): 1369. CrossRef
Immune checkpoint inhibitor-related pneumonitis in non-small cell lung cancer: A review
Yuxuan Hao, Xiaoye Zhang, Li Yu
Frontiers in Oncology.2022;[Epub] CrossRef
Improving Time-to-Treatment for Advanced Non-Small Cell Lung Cancer Patients through Faster Single Gene EGFR Testing Using the Idylla™ EGFR Testing Platform
Norbert Banyi, Deepu Alex, Curtis Hughesman, Kelly McNeil, Diana N. Ionescu, Carmen Ma, Stephen Yip, Barbara Melosky
Current Oncology.2022; 29(10): 7900. CrossRef
Sequential or combined immune checkpoint inhibitors and targeted therapy: Navigating uncharted waters
K. El Husseini, M. Wislez
Respiratory Medicine and Research.2021; 79: 100820. CrossRef
Multiple drugs

Reactions Weekly.2021; 1863(1): 255. CrossRef
Deep learning model enables the discovery of a novel immunotherapeutic agent regulating the kynurenine pathway
Jeong Hun Kim, Won Suk Lee, Hye Jin Lee, Hannah Yang, Seung Joon Lee, So Jung Kong, Soyeon Je, Hyun-Jin Yang, Jongsun Jung, Jaekyung Cheon, Beodeul Kang, Hong Jae Chon, Chan Kim
OncoImmunology.2021;[Epub] CrossRef

7,917 View
202 Download
9 Web of Science
9 Crossref

First
Prev
Page of 1
Next
Last

Search