Personalized circulating tumor DNA detection to monitor immunotherapy efficacy and predict outcome in locally advanced or metastatic non‐small cell lung cancer
Abstract Objective Immune checkpoint inhibitors (ICIs) or combined with chemotherapy exhibit substantial efficacy for the treatment of advanced non‐small cell lung cancer (NSCLC). However, reliable biomarkers that can monitor response to first‐line ICIs ± chemotherapy remain unclear. Methods A total...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-07-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.6108 |
| _version_ | 1797776422198050816 |
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| author | Lei Cheng Guanghui Gao Chao Zhao Haowei Wang Chao Yao Hanchuanzhi Yu Jichen Yao Feng Li Lijie Guo Qijie Jian Xiaoxia Chen Xuefei Li Caicun Zhou |
| author_facet | Lei Cheng Guanghui Gao Chao Zhao Haowei Wang Chao Yao Hanchuanzhi Yu Jichen Yao Feng Li Lijie Guo Qijie Jian Xiaoxia Chen Xuefei Li Caicun Zhou |
| author_sort | Lei Cheng |
| collection | DOAJ |
| description | Abstract Objective Immune checkpoint inhibitors (ICIs) or combined with chemotherapy exhibit substantial efficacy for the treatment of advanced non‐small cell lung cancer (NSCLC). However, reliable biomarkers that can monitor response to first‐line ICIs ± chemotherapy remain unclear. Methods A total of 16 tumor tissues and 46 matched peripheral blood samples at baseline and during treatment were retrospectively collected from 19 locally advanced or metastatic NSCLC patients. The circulating tumor DNA (ctDNA) burden by tumor‐informed assay was detected to monitor and predict the therapeutic response and survival of NSCLC patients treated with first‐line ICIs or plus chemotherapy. Results We found that ctDNA was only positively detected in one patient by tumor‐agnostic assay with a mean variant allele fraction (VAF) of 6.40%, whereas it was positively detected in three patients by tumor‐informed assay with a mean VAF of 8.83%, 0.154%, and 0.176%, respectively. Tumor‐informed assays could sensitively detect ctDNA in 93.75% (15/16) of patients. Trends in the level of ctDNA from baseline to first evaluation was consistent with the radiographic changes. There was a greater decrease in ctDNA after treatment compared with baseline in patients with partial response compared to patients with stable disease/progressive disease. Patients with over a 50% reduction in ctDNA had a significant progression‐free survival and overall survival benefit. Conclusion The tumor‐informed assay was favorable for ctDNA detection, and early dynamic changes in plasma ctDNA may be a valuable biomarker for monitoring the efficacy and predicting the outcome in advanced NSCLC patients treated with first‐line ICIs ± chemotherapy. |
| first_indexed | 2024-03-12T22:49:45Z |
| format | Article |
| id | doaj.art-0f379d897ec44114bfb86ea98faa89b4 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-03-12T22:49:45Z |
| publishDate | 2023-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-0f379d897ec44114bfb86ea98faa89b42023-07-20T12:57:16ZengWileyCancer Medicine2045-76342023-07-011213143171432610.1002/cam4.6108Personalized circulating tumor DNA detection to monitor immunotherapy efficacy and predict outcome in locally advanced or metastatic non‐small cell lung cancerLei Cheng0Guanghui Gao1Chao Zhao2Haowei Wang3Chao Yao4Hanchuanzhi Yu5Jichen Yao6Feng Li7Lijie Guo8Qijie Jian9Xiaoxia Chen10Xuefei Li11Caicun Zhou12Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, School of Medicine Tongji University Shanghai ChinaDepartment of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine Tongji University Shanghai ChinaDepartment of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, School of Medicine Tongji University Shanghai ChinaDepartment of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine Tongji University Shanghai ChinaOrigiMed Co., Ltd Shanghai ChinaOrigiMed Co., Ltd Shanghai ChinaOrigiMed Co., Ltd Shanghai ChinaOrigiMed Co., Ltd Shanghai ChinaOrigiMed Co., Ltd Shanghai ChinaOrigiMed Co., Ltd Shanghai ChinaDepartment of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine Tongji University Shanghai ChinaDepartment of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, School of Medicine Tongji University Shanghai ChinaDepartment of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine Tongji University Shanghai ChinaAbstract Objective Immune checkpoint inhibitors (ICIs) or combined with chemotherapy exhibit substantial efficacy for the treatment of advanced non‐small cell lung cancer (NSCLC). However, reliable biomarkers that can monitor response to first‐line ICIs ± chemotherapy remain unclear. Methods A total of 16 tumor tissues and 46 matched peripheral blood samples at baseline and during treatment were retrospectively collected from 19 locally advanced or metastatic NSCLC patients. The circulating tumor DNA (ctDNA) burden by tumor‐informed assay was detected to monitor and predict the therapeutic response and survival of NSCLC patients treated with first‐line ICIs or plus chemotherapy. Results We found that ctDNA was only positively detected in one patient by tumor‐agnostic assay with a mean variant allele fraction (VAF) of 6.40%, whereas it was positively detected in three patients by tumor‐informed assay with a mean VAF of 8.83%, 0.154%, and 0.176%, respectively. Tumor‐informed assays could sensitively detect ctDNA in 93.75% (15/16) of patients. Trends in the level of ctDNA from baseline to first evaluation was consistent with the radiographic changes. There was a greater decrease in ctDNA after treatment compared with baseline in patients with partial response compared to patients with stable disease/progressive disease. Patients with over a 50% reduction in ctDNA had a significant progression‐free survival and overall survival benefit. Conclusion The tumor‐informed assay was favorable for ctDNA detection, and early dynamic changes in plasma ctDNA may be a valuable biomarker for monitoring the efficacy and predicting the outcome in advanced NSCLC patients treated with first‐line ICIs ± chemotherapy.https://doi.org/10.1002/cam4.6108circulating tumor DNAimmune checkpoint inhibitorsmonitoring efficacynon‐small cell lung canceroutcome prediction |
| spellingShingle | Lei Cheng Guanghui Gao Chao Zhao Haowei Wang Chao Yao Hanchuanzhi Yu Jichen Yao Feng Li Lijie Guo Qijie Jian Xiaoxia Chen Xuefei Li Caicun Zhou Personalized circulating tumor DNA detection to monitor immunotherapy efficacy and predict outcome in locally advanced or metastatic non‐small cell lung cancer Cancer Medicine circulating tumor DNA immune checkpoint inhibitors monitoring efficacy non‐small cell lung cancer outcome prediction |
| title | Personalized circulating tumor DNA detection to monitor immunotherapy efficacy and predict outcome in locally advanced or metastatic non‐small cell lung cancer |
| title_full | Personalized circulating tumor DNA detection to monitor immunotherapy efficacy and predict outcome in locally advanced or metastatic non‐small cell lung cancer |
| title_fullStr | Personalized circulating tumor DNA detection to monitor immunotherapy efficacy and predict outcome in locally advanced or metastatic non‐small cell lung cancer |
| title_full_unstemmed | Personalized circulating tumor DNA detection to monitor immunotherapy efficacy and predict outcome in locally advanced or metastatic non‐small cell lung cancer |
| title_short | Personalized circulating tumor DNA detection to monitor immunotherapy efficacy and predict outcome in locally advanced or metastatic non‐small cell lung cancer |
| title_sort | personalized circulating tumor dna detection to monitor immunotherapy efficacy and predict outcome in locally advanced or metastatic non small cell lung cancer |
| topic | circulating tumor DNA immune checkpoint inhibitors monitoring efficacy non‐small cell lung cancer outcome prediction |
| url | https://doi.org/10.1002/cam4.6108 |
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