Monitoring the effect of first line treatment in RAS/RAF mutated metastatic colorectal cancer by serial analysis of tumor specific DNA in plasma

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

95 Downloads (Pure)

Resumé

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.

OriginalsprogEngelsk
Artikelnummer55
TidsskriftJournal of Experimental and Clinical Cancer Research (Online)
Vol/bind37
Udgave nummer1
Antal sider7
ISSN1756-9966
DOI
StatusUdgivet - 2018

Fingeraftryk

Colorectal Neoplasms
DNA
Neoplasms
Precision Medicine
Mutation
Prospective Studies
Polymerase Chain Reaction

Emneord

  • colorectal cancer
  • RAS/RAF mutation
  • cirkulerende tumor DNA

Citer dette

@article{ec37c75c2caa40d89bc4b79d0c65b198,
title = "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 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.",
keywords = "colorectal cancer, RAS/RAF mutation, cirkulerende tumor DNA, Journal Article, Treatment efficiency, RAS/RAF mutations, Liquid biopsy, Circulating tumor DNA, Metastatic colorectal cancer, Monitoring",
author = "{Brenner Thomsen}, {Caroline Emilie} and Hansen, {T F} and Andersen, {R F} and J Lindebjerg and Jensen, {L H} and A Jakobsen",
year = "2018",
doi = "10.1186/s13046-018-0723-5",
language = "English",
volume = "37",
journal = "Journal of Experimental and Clinical Cancer Research (Online)",
issn = "1756-9966",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Monitoring the effect of first line treatment in RAS/RAF mutated metastatic colorectal cancer by serial analysis of tumor specific DNA in plasma

AU - Brenner Thomsen, Caroline Emilie

AU - Hansen, T F

AU - Andersen, R F

AU - Lindebjerg, J

AU - Jensen, L H

AU - Jakobsen, A

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - colorectal cancer

KW - RAS/RAF mutation

KW - cirkulerende tumor DNA

KW - Journal Article

KW - Treatment efficiency

KW - RAS/RAF mutations

KW - Liquid biopsy

KW - Circulating tumor DNA

KW - Metastatic colorectal cancer

KW - Monitoring

U2 - 10.1186/s13046-018-0723-5

DO - 10.1186/s13046-018-0723-5

M3 - Journal article

VL - 37

JO - Journal of Experimental and Clinical Cancer Research (Online)

JF - Journal of Experimental and Clinical Cancer Research (Online)

SN - 1756-9966

IS - 1

M1 - 55

ER -