Improved Pathologic response to chemoradiation in MGMT methylated locally advanced rectal cancer
Background and Purpose: With the growing interest in total neoadjuvant treatment for locally advanced rectal adenocarcinoma (LARC) there is an urgent unmet need to identify predictive markers of response to long-course neoadjuvant concurrent chemoradiotherapy (LCRT). O6-Methylguanine (O6-MG)-DNA-met...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Clinical and Translational Radiation Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405630823000927 |
| _version_ | 1797731058135859200 |
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| author | Garrett L. Jensen Niloufar Pourfarrokh Marcus Volz Linden L. Morales Kimberly Walker Kendall P. Hammonds Moataz El-Ghamry Lucas Wong Parsa Hodjat Eduardo Castro Arundhati Rao Sameer G. Jhavar |
| author_facet | Garrett L. Jensen Niloufar Pourfarrokh Marcus Volz Linden L. Morales Kimberly Walker Kendall P. Hammonds Moataz El-Ghamry Lucas Wong Parsa Hodjat Eduardo Castro Arundhati Rao Sameer G. Jhavar |
| author_sort | Garrett L. Jensen |
| collection | DOAJ |
| description | Background and Purpose: With the growing interest in total neoadjuvant treatment for locally advanced rectal adenocarcinoma (LARC) there is an urgent unmet need to identify predictive markers of response to long-course neoadjuvant concurrent chemoradiotherapy (LCRT). O6-Methylguanine (O6-MG)-DNA-methyltransferase (MGMT) gene methylation has been associated in some malignancies with response to concurrent chemoradiotherapy. We attempted to find if pathologic response to LCRT was associated with MGMT promoter hypermethylation (MGMTh). Materials and Methods: Patients were identified with LARC, available pre-treatment biopsy specimens, and at least 1 year of follow-up who received LCRT followed by surgical resection within 6 months. Biopsies were tested for MGMTh using a Qiagen pyrosequencing kit (Catalog number 970061). The primary outcome of LCRT responsiveness was based on tumor regression grade (TRG), with grades of 0–1 considered to have excellent response and grades of 2–3 considered to be non-responders. Secondary outcomes included overall survival (OS) and recurrence free survival (RFS). Results: Of 96 patients who met inclusion criteria, 76 had samples which produced reliable assay results. MGMTh corresponded with higher grade and age of the biopsy specimen. The percentage of responders to LCRT was higher amongst the MGMTh patients than the MGMTn patients (60.0% vs 27.5%, p value = 0.0061). MGMTh was not significantly associated with improved OS (2-year OS of 96.0% vs 98.0%, p = 0.8102) but there was a trend for improved RFS (2-year RFS of 87.6% vs 74.2%, p = 0.0903). Conclusion: Significantly greater tumor regression following LCRT was seen in MGMTh LARC. Methylation status may help identify good candidates for close observation without surgery following LCRT. |
| first_indexed | 2024-03-12T11:52:48Z |
| format | Article |
| id | doaj.art-f7352f961bcd44ee9dc960b2ab7c892d |
| institution | Directory Open Access Journal |
| issn | 2405-6308 |
| language | English |
| last_indexed | 2024-03-12T11:52:48Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Clinical and Translational Radiation Oncology |
| spelling | doaj.art-f7352f961bcd44ee9dc960b2ab7c892d2023-08-31T05:03:25ZengElsevierClinical and Translational Radiation Oncology2405-63082023-09-0142100667Improved Pathologic response to chemoradiation in MGMT methylated locally advanced rectal cancerGarrett L. Jensen0Niloufar Pourfarrokh1Marcus Volz2Linden L. Morales3Kimberly Walker4Kendall P. Hammonds5Moataz El-Ghamry6Lucas Wong7Parsa Hodjat8Eduardo Castro9Arundhati Rao10Sameer G. Jhavar11Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN, USADepartments of Pathology, Baylor Scott & White Health, 2401 S. 31st St., Temple, TX 76508, USADepartments of Pathology, Baylor Scott & White Health, 2401 S. 31st St., Temple, TX 76508, USADepartments of Pathology, Baylor Scott & White Health, 2401 S. 31st St., Temple, TX 76508, USADepartments of Pathology, Baylor Scott & White Health, 2401 S. 31st St., Temple, TX 76508, USABiostatistics, Baylor Scott & White Health, 2401 S. 31st St., Temple, TX 76508, USARadiation Oncology, Baylor Scott & White Health, 2401 S. 31st St., Temple, TX 76508, USAMedical Oncology, Baylor Scott & White Health, 2401 S. 31st St., Temple, TX 76508, USADepartment of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston TX, USADepartments of Pathology, Baylor Scott & White Health, 2401 S. 31st St., Temple, TX 76508, USADepartments of Pathology, Baylor Scott & White Health, 2401 S. 31st St., Temple, TX 76508, USARadiation Oncology, Baylor Scott & White Health, 2401 S. 31st St., Temple, TX 76508, USA; Corresponding author.Background and Purpose: With the growing interest in total neoadjuvant treatment for locally advanced rectal adenocarcinoma (LARC) there is an urgent unmet need to identify predictive markers of response to long-course neoadjuvant concurrent chemoradiotherapy (LCRT). O6-Methylguanine (O6-MG)-DNA-methyltransferase (MGMT) gene methylation has been associated in some malignancies with response to concurrent chemoradiotherapy. We attempted to find if pathologic response to LCRT was associated with MGMT promoter hypermethylation (MGMTh). Materials and Methods: Patients were identified with LARC, available pre-treatment biopsy specimens, and at least 1 year of follow-up who received LCRT followed by surgical resection within 6 months. Biopsies were tested for MGMTh using a Qiagen pyrosequencing kit (Catalog number 970061). The primary outcome of LCRT responsiveness was based on tumor regression grade (TRG), with grades of 0–1 considered to have excellent response and grades of 2–3 considered to be non-responders. Secondary outcomes included overall survival (OS) and recurrence free survival (RFS). Results: Of 96 patients who met inclusion criteria, 76 had samples which produced reliable assay results. MGMTh corresponded with higher grade and age of the biopsy specimen. The percentage of responders to LCRT was higher amongst the MGMTh patients than the MGMTn patients (60.0% vs 27.5%, p value = 0.0061). MGMTh was not significantly associated with improved OS (2-year OS of 96.0% vs 98.0%, p = 0.8102) but there was a trend for improved RFS (2-year RFS of 87.6% vs 74.2%, p = 0.0903). Conclusion: Significantly greater tumor regression following LCRT was seen in MGMTh LARC. Methylation status may help identify good candidates for close observation without surgery following LCRT.http://www.sciencedirect.com/science/article/pii/S2405630823000927MGMTAlkylatingChemosensitiveMethylationRadiosensitive |
| spellingShingle | Garrett L. Jensen Niloufar Pourfarrokh Marcus Volz Linden L. Morales Kimberly Walker Kendall P. Hammonds Moataz El-Ghamry Lucas Wong Parsa Hodjat Eduardo Castro Arundhati Rao Sameer G. Jhavar Improved Pathologic response to chemoradiation in MGMT methylated locally advanced rectal cancer Clinical and Translational Radiation Oncology MGMT Alkylating Chemosensitive Methylation Radiosensitive |
| title | Improved Pathologic response to chemoradiation in MGMT methylated locally advanced rectal cancer |
| title_full | Improved Pathologic response to chemoradiation in MGMT methylated locally advanced rectal cancer |
| title_fullStr | Improved Pathologic response to chemoradiation in MGMT methylated locally advanced rectal cancer |
| title_full_unstemmed | Improved Pathologic response to chemoradiation in MGMT methylated locally advanced rectal cancer |
| title_short | Improved Pathologic response to chemoradiation in MGMT methylated locally advanced rectal cancer |
| title_sort | improved pathologic response to chemoradiation in mgmt methylated locally advanced rectal cancer |
| topic | MGMT Alkylating Chemosensitive Methylation Radiosensitive |
| url | http://www.sciencedirect.com/science/article/pii/S2405630823000927 |
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