Monitoring the effect of first line treatment in RAS/RAF mutated metastatic colorectal cancer by serial analysis of tumor specific DNA in plasma
Abstract Background Precision medicine calls for an early indicator of treatment efficiency. Circulating tumor DNA (ctDNA) is a promising marker in this setting. Our prospective study explored the association between disease development and change of ctDNA during first line chemotherapy in patients...
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| Format: | Article |
| Language: | English |
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BMC
2018-03-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13046-018-0723-5 |
| _version_ | 1818519362593619968 |
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| author | C. B. Thomsen T. F. Hansen R. F. Andersen J. Lindebjerg L. H. Jensen A. Jakobsen |
| author_facet | C. B. Thomsen T. F. Hansen R. F. Andersen J. Lindebjerg L. H. Jensen A. Jakobsen |
| author_sort | C. B. Thomsen |
| collection | DOAJ |
| description | Abstract Background Precision medicine calls for an early indicator of treatment efficiency. Circulating tumor DNA (ctDNA) is a promising marker in this setting. Our prospective study explored the association between disease development and change of ctDNA during first line chemotherapy in patients with RAS/RAF mutated metastatic colorectal cancer (mCRC). Methods The study included 138 patients with mCRC receiving standard first line treatment. In patients with RAS/RAF mutated tumor DNA the same mutation was quantified in the plasma using droplet digital PCR. The fractional abundance of ctDNA was assessed in plasma before treatment start and at every treatment cycle until radiologically defined progressive disease. Results RAS/RAF mutations were detected in the plasma from 77 patients. Twenty patients progressed on treatment and 57 stopped treatment without progression. The presence of mutated DNA in plasma was correlated with poor overall survival. A low level of ctDNA after the first cycle of chemotherapy was associated with a low risk of progression. On the other hand, a significant increase of ctDNA at any time during the treatment course was associated with a high risk of progression on continuous treatment. The first increase in ctDNA level occurred at a median of 51 days before radiologically confirmed progression. Conclusions The results indicate that the ctDNA level holds potential as a clinically valuable marker in first line treatment of mCRC. A rapid decrease was associated with a prolonged progression free interval, whereas a significant increase gave notice of early progression with a relevant lead time. |
| first_indexed | 2024-12-11T01:23:15Z |
| format | Article |
| id | doaj.art-9ea9b0dfc7684dd3a339893c931f4403 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-11T01:23:15Z |
| publishDate | 2018-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-9ea9b0dfc7684dd3a339893c931f44032022-12-22T01:25:39ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662018-03-013711710.1186/s13046-018-0723-5Monitoring the effect of first line treatment in RAS/RAF mutated metastatic colorectal cancer by serial analysis of tumor specific DNA in plasmaC. B. Thomsen0T. F. Hansen1R. F. Andersen2J. Lindebjerg3L. H. Jensen4A. Jakobsen5Danish Colorectal Cancer Center South, Vejle HospitalDanish Colorectal Cancer Center South, Vejle HospitalDanish Colorectal Cancer Center South, Vejle HospitalDanish Colorectal Cancer Center South, Vejle HospitalDanish Colorectal Cancer Center South, Vejle HospitalDanish Colorectal Cancer Center South, Vejle HospitalAbstract Background Precision medicine calls for an early indicator of treatment efficiency. Circulating tumor DNA (ctDNA) is a promising marker in this setting. Our prospective study explored the association between disease development and change of ctDNA during first line chemotherapy in patients with RAS/RAF mutated metastatic colorectal cancer (mCRC). Methods The study included 138 patients with mCRC receiving standard first line treatment. In patients with RAS/RAF mutated tumor DNA the same mutation was quantified in the plasma using droplet digital PCR. The fractional abundance of ctDNA was assessed in plasma before treatment start and at every treatment cycle until radiologically defined progressive disease. Results RAS/RAF mutations were detected in the plasma from 77 patients. Twenty patients progressed on treatment and 57 stopped treatment without progression. The presence of mutated DNA in plasma was correlated with poor overall survival. A low level of ctDNA after the first cycle of chemotherapy was associated with a low risk of progression. On the other hand, a significant increase of ctDNA at any time during the treatment course was associated with a high risk of progression on continuous treatment. The first increase in ctDNA level occurred at a median of 51 days before radiologically confirmed progression. Conclusions The results indicate that the ctDNA level holds potential as a clinically valuable marker in first line treatment of mCRC. A rapid decrease was associated with a prolonged progression free interval, whereas a significant increase gave notice of early progression with a relevant lead time.http://link.springer.com/article/10.1186/s13046-018-0723-5Circulating tumor DNARAS/RAF mutationsMetastatic colorectal cancerLiquid biopsyMonitoringTreatment efficiency |
| spellingShingle | C. B. Thomsen T. F. Hansen R. F. Andersen J. Lindebjerg L. H. Jensen A. Jakobsen Monitoring the effect of first line treatment in RAS/RAF mutated metastatic colorectal cancer by serial analysis of tumor specific DNA in plasma Journal of Experimental & Clinical Cancer Research Circulating tumor DNA RAS/RAF mutations Metastatic colorectal cancer Liquid biopsy Monitoring Treatment efficiency |
| title | Monitoring the effect of first line treatment in RAS/RAF mutated metastatic colorectal cancer by serial analysis of tumor specific DNA in plasma |
| title_full | Monitoring the effect of first line treatment in RAS/RAF mutated metastatic colorectal cancer by serial analysis of tumor specific DNA in plasma |
| title_fullStr | Monitoring the effect of first line treatment in RAS/RAF mutated metastatic colorectal cancer by serial analysis of tumor specific DNA in plasma |
| title_full_unstemmed | Monitoring the effect of first line treatment in RAS/RAF mutated metastatic colorectal cancer by serial analysis of tumor specific DNA in plasma |
| title_short | Monitoring the effect of first line treatment in RAS/RAF mutated metastatic colorectal cancer by serial analysis of tumor specific DNA in plasma |
| title_sort | monitoring the effect of first line treatment in ras raf mutated metastatic colorectal cancer by serial analysis of tumor specific dna in plasma |
| topic | Circulating tumor DNA RAS/RAF mutations Metastatic colorectal cancer Liquid biopsy Monitoring Treatment efficiency |
| url | http://link.springer.com/article/10.1186/s13046-018-0723-5 |
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