Long-term survival and undetectable circulating tumor DNA following comprehensive involved site radiotherapy for oligometastases

Abstract Distant metastases account for ~ 90% of cancer deaths and major responses with systemic therapy alone for metastatic cancers are so rare that the National Cancer Institute launched the Exceptional Responders Initiative. Comprehensive involved site radiotherapy (ISRT) is a promising treatmen...

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Main Authors: Rachel Radigan, Caleb S. Kao, Michael Krainock, Minetta C. Liu, Vani Gupta, Lauren Alexander, Symeon Missios, John Hsu, Ashish Sangal, Michael T. Milano, Johnny Kao
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-88266-z
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author Rachel Radigan
Caleb S. Kao
Michael Krainock
Minetta C. Liu
Vani Gupta
Lauren Alexander
Symeon Missios
John Hsu
Ashish Sangal
Michael T. Milano
Johnny Kao
author_facet Rachel Radigan
Caleb S. Kao
Michael Krainock
Minetta C. Liu
Vani Gupta
Lauren Alexander
Symeon Missios
John Hsu
Ashish Sangal
Michael T. Milano
Johnny Kao
author_sort Rachel Radigan
collection DOAJ
description Abstract Distant metastases account for ~ 90% of cancer deaths and major responses with systemic therapy alone for metastatic cancers are so rare that the National Cancer Institute launched the Exceptional Responders Initiative. Comprehensive involved site radiotherapy (ISRT) is a promising treatment for oligometastases but the role of circulating tumor DNA to confirm durable molecular response following treatment remains unexplored. Among 597 consecutive patients with distant metastases treated with radiation therapy from 2014 to 2021, 133 (22%) were oligometastatic and 464 (78%) were polymetastatic. The 5-year overall survival was 38% for oligometastases vs. 3% for polymetastases (p < 0.001). At a median follow-up of 71 months for treated oligometastases, 37 (28%) exceptional responders (ER) remain alive and recurrence free at ≥ 2 year follow-up. Among ER, 49% underwent stereotactic radiotherapy (median 27 Gy in 3 fractions, EQD2 43 Gy), 65% underwent intensity-modulated radiation therapy (median 53 Gy in 24 fractions, EQD2 54 Gy), and 76% received additional systemic therapy. Although ctDNA testing was not possible in most ER due to patient refusal or tumor specimen quality, all 12 ER tested ctDNA-negative. Long-term complete responses, including molecular complete responses, are achievable with comprehensive ISRT in diverse clinical presentations.
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spelling doaj-art-aff72594597f47e9995bf83bf13458622025-08-20T01:56:01ZengNature PortfolioScientific Reports2045-23222025-02-0115111410.1038/s41598-025-88266-zLong-term survival and undetectable circulating tumor DNA following comprehensive involved site radiotherapy for oligometastasesRachel Radigan0Caleb S. Kao1Michael Krainock2Minetta C. Liu3Vani Gupta4Lauren Alexander5Symeon Missios6John Hsu7Ashish Sangal8Michael T. Milano9Johnny Kao10New York Institute of Technology College of Osteopathic MedicineGood Samaritan University HospitalNatera (United States)Natera (United States)New York Institute of Technology College of Osteopathic MedicineGood Samaritan University HospitalGood Samaritan University HospitalGood Samaritan University HospitalGood Samaritan University HospitalUniversity of Rochester Medical CenterNew York Institute of Technology College of Osteopathic MedicineAbstract Distant metastases account for ~ 90% of cancer deaths and major responses with systemic therapy alone for metastatic cancers are so rare that the National Cancer Institute launched the Exceptional Responders Initiative. Comprehensive involved site radiotherapy (ISRT) is a promising treatment for oligometastases but the role of circulating tumor DNA to confirm durable molecular response following treatment remains unexplored. Among 597 consecutive patients with distant metastases treated with radiation therapy from 2014 to 2021, 133 (22%) were oligometastatic and 464 (78%) were polymetastatic. The 5-year overall survival was 38% for oligometastases vs. 3% for polymetastases (p < 0.001). At a median follow-up of 71 months for treated oligometastases, 37 (28%) exceptional responders (ER) remain alive and recurrence free at ≥ 2 year follow-up. Among ER, 49% underwent stereotactic radiotherapy (median 27 Gy in 3 fractions, EQD2 43 Gy), 65% underwent intensity-modulated radiation therapy (median 53 Gy in 24 fractions, EQD2 54 Gy), and 76% received additional systemic therapy. Although ctDNA testing was not possible in most ER due to patient refusal or tumor specimen quality, all 12 ER tested ctDNA-negative. Long-term complete responses, including molecular complete responses, are achievable with comprehensive ISRT in diverse clinical presentations.https://doi.org/10.1038/s41598-025-88266-z
spellingShingle Rachel Radigan
Caleb S. Kao
Michael Krainock
Minetta C. Liu
Vani Gupta
Lauren Alexander
Symeon Missios
John Hsu
Ashish Sangal
Michael T. Milano
Johnny Kao
Long-term survival and undetectable circulating tumor DNA following comprehensive involved site radiotherapy for oligometastases
Scientific Reports
title Long-term survival and undetectable circulating tumor DNA following comprehensive involved site radiotherapy for oligometastases
title_full Long-term survival and undetectable circulating tumor DNA following comprehensive involved site radiotherapy for oligometastases
title_fullStr Long-term survival and undetectable circulating tumor DNA following comprehensive involved site radiotherapy for oligometastases
title_full_unstemmed Long-term survival and undetectable circulating tumor DNA following comprehensive involved site radiotherapy for oligometastases
title_short Long-term survival and undetectable circulating tumor DNA following comprehensive involved site radiotherapy for oligometastases
title_sort long term survival and undetectable circulating tumor dna following comprehensive involved site radiotherapy for oligometastases
url https://doi.org/10.1038/s41598-025-88266-z
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