Assessment of tumor burden and response to therapy in patients with colorectal cancer using a quantitative ctDNA test for methylated BCAT1/IKZF1
Failure of colorectal cancer (CRC) treatment is due to residual disease, and its timely identification is critical for patient survival. Detecting CRC‐associated mutations in patient circulating cell‐free DNA is confounded by tumor mutation heterogeneity, requiring primary tumor sequencing to identi...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-05-01
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| Series: | Molecular Oncology |
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| Online Access: | https://doi.org/10.1002/1878-0261.13178 |
| _version_ | 1818215475680641024 |
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| author | Erin L. Symonds Susanne K. Pedersen Bernita Yeo Hiba Al Naji Susan E. Byrne Amitesh Roy Graeme P. Young |
| author_facet | Erin L. Symonds Susanne K. Pedersen Bernita Yeo Hiba Al Naji Susan E. Byrne Amitesh Roy Graeme P. Young |
| author_sort | Erin L. Symonds |
| collection | DOAJ |
| description | Failure of colorectal cancer (CRC) treatment is due to residual disease, and its timely identification is critical for patient survival. Detecting CRC‐associated mutations in patient circulating cell‐free DNA is confounded by tumor mutation heterogeneity, requiring primary tumor sequencing to identify relevant mutations. In this study, we assessed BCAT1 and IKZF1 methylation levels to quantify circulating tumor DNA (ctDNA) and investigated whether this method can be used to assess tumor burden and efficacy of therapy. In 175 patients with CRC who were ctDNA‐positive pretreatment, ctDNA levels were higher with advancing stage (P < 0.05) and correlated with tumor diameter (r = 0.35, P < 0.001) and volume (r = 0.58, P < 0.01). After completion of treatment (median of 70 days [IQR 49‐109] after surgery, +/− radiotherapy, +/− chemotherapy), ctDNA levels were reduced in 98% (47/48) and were undetectable in 88% (42/48) of patients tested. For those with incomplete adjuvant chemotherapy after surgery, roughly half remained ctDNA‐positive (11/21, 52.4%). The presence of ctDNA after treatment was associated with disease progression (HR 9.7, 95%CI 2.5‐37.6) compared to no ctDNA. Assaying blood for ctDNA methylated in BCAT1/IKZF1 has the potential for identifying residual disease due to treatment failure, informing a potential need for therapy adjustment in advanced disease. |
| first_indexed | 2024-12-12T06:36:40Z |
| format | Article |
| id | doaj.art-e0303109940445d796b258f66148e63f |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-12-12T06:36:40Z |
| publishDate | 2022-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-e0303109940445d796b258f66148e63f2022-12-22T00:34:27ZengWileyMolecular Oncology1574-78911878-02612022-05-0116102031204110.1002/1878-0261.13178Assessment of tumor burden and response to therapy in patients with colorectal cancer using a quantitative ctDNA test for methylated BCAT1/IKZF1Erin L. Symonds0Susanne K. Pedersen1Bernita Yeo2Hiba Al Naji3Susan E. Byrne4Amitesh Roy5Graeme P. Young6Bowel Health Service Flinders Medical Centre Bedford Park AustraliaCancer Research Flinders Health and Medical Research Institute Flinders University Bedford Park AustraliaDepartment of Medicine College of Medicine and Public Health Flinders University Bedford Park AustraliaDepartment of Medicine College of Medicine and Public Health Flinders University Bedford Park AustraliaCancer Research Flinders Health and Medical Research Institute Flinders University Bedford Park AustraliaCancer Research Flinders Health and Medical Research Institute Flinders University Bedford Park AustraliaCancer Research Flinders Health and Medical Research Institute Flinders University Bedford Park AustraliaFailure of colorectal cancer (CRC) treatment is due to residual disease, and its timely identification is critical for patient survival. Detecting CRC‐associated mutations in patient circulating cell‐free DNA is confounded by tumor mutation heterogeneity, requiring primary tumor sequencing to identify relevant mutations. In this study, we assessed BCAT1 and IKZF1 methylation levels to quantify circulating tumor DNA (ctDNA) and investigated whether this method can be used to assess tumor burden and efficacy of therapy. In 175 patients with CRC who were ctDNA‐positive pretreatment, ctDNA levels were higher with advancing stage (P < 0.05) and correlated with tumor diameter (r = 0.35, P < 0.001) and volume (r = 0.58, P < 0.01). After completion of treatment (median of 70 days [IQR 49‐109] after surgery, +/− radiotherapy, +/− chemotherapy), ctDNA levels were reduced in 98% (47/48) and were undetectable in 88% (42/48) of patients tested. For those with incomplete adjuvant chemotherapy after surgery, roughly half remained ctDNA‐positive (11/21, 52.4%). The presence of ctDNA after treatment was associated with disease progression (HR 9.7, 95%CI 2.5‐37.6) compared to no ctDNA. Assaying blood for ctDNA methylated in BCAT1/IKZF1 has the potential for identifying residual disease due to treatment failure, informing a potential need for therapy adjustment in advanced disease.https://doi.org/10.1002/1878-0261.13178BCAT1circulating tumor DNAcolorectal cancerefficacyIKZF1methylation |
| spellingShingle | Erin L. Symonds Susanne K. Pedersen Bernita Yeo Hiba Al Naji Susan E. Byrne Amitesh Roy Graeme P. Young Assessment of tumor burden and response to therapy in patients with colorectal cancer using a quantitative ctDNA test for methylated BCAT1/IKZF1 Molecular Oncology BCAT1 circulating tumor DNA colorectal cancer efficacy IKZF1 methylation |
| title | Assessment of tumor burden and response to therapy in patients with colorectal cancer using a quantitative ctDNA test for methylated BCAT1/IKZF1 |
| title_full | Assessment of tumor burden and response to therapy in patients with colorectal cancer using a quantitative ctDNA test for methylated BCAT1/IKZF1 |
| title_fullStr | Assessment of tumor burden and response to therapy in patients with colorectal cancer using a quantitative ctDNA test for methylated BCAT1/IKZF1 |
| title_full_unstemmed | Assessment of tumor burden and response to therapy in patients with colorectal cancer using a quantitative ctDNA test for methylated BCAT1/IKZF1 |
| title_short | Assessment of tumor burden and response to therapy in patients with colorectal cancer using a quantitative ctDNA test for methylated BCAT1/IKZF1 |
| title_sort | assessment of tumor burden and response to therapy in patients with colorectal cancer using a quantitative ctdna test for methylated bcat1 ikzf1 |
| topic | BCAT1 circulating tumor DNA colorectal cancer efficacy IKZF1 methylation |
| url | https://doi.org/10.1002/1878-0261.13178 |
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