File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Circulating Tumor DNA Dynamics as Prognostic Markers in Locally Advanced and Metastatic Esophageal Squamous Cell Carcinoma

TitleCirculating Tumor DNA Dynamics as Prognostic Markers in Locally Advanced and Metastatic Esophageal Squamous Cell Carcinoma
Authors
Issue Date20-Sep-2023
PublisherAmerican Medical Association
Citation
JAMA Surgery, 2023 How to Cite?
Abstract

Importance  Esophageal squamous cell carcinoma (ESCC) is a deadly disease with frequent recurrence. There are unmet needs for prognostic biomarkers for dynamically monitoring disease progression and detecting minimal residual disease.

Objective  To examine whether circulating tumor DNA is clinically useful as a prognostic biomarker for ESCC recurrence and patient survival.

Design, Setting, and Participants  This single-center, population-based cohort study consecutively enrolled 147 patients receiving curative (n = 74) or palliative (n = 73) treatment at the surgery and clinical oncology departments of Queen Mary Hospital in Hong Kong from August 1, 2016, to September 31, 2021. Patients were followed up for 2 years. Plasma samples were collected at different longitudinal time points for a prospective circulating tumor DNA (ctDNA) next-generation sequencing profiling study of 77 actionable genes.

Intervention  Patients were treated with up-front surgery, neoadjuvant chemoradiotherapy plus surgery with or without adjuvant therapy, or palliative chemotherapy (CT).

Main Outcomes and Measures  Detection of circulating tumor DNA (ctDNA), progression-free survival (PFS), and overall survival (OS).

Results  A total of 478 serial plasma samples from 147 patients with locoregional or metastatic ESCC were prospectively analyzed. Among the 74 patients in the curative group (median [range] age, 66 [46-85] years; 56 [76.0%] male), 44 (59.5%) relapsed and 36 (48.6%) died. For patients receiving curative surgical treatment, a high ctDNA level (hazard ratio [HR], 7.84; 95% CI, 1.87-32.97; P = .005) and ctDNA alterations (HR, 5.71; 95% CI, 1.81-17.97; P = .003) at 6 months postoperation were independently associated with poor OS. Among patients receiving neoadjuvant chemoradiotherapy, postneoadjuvant ctDNA alterations were associated with poor PFS (HR, 3.16; 95% CI, 1.17-8.52; P = .02). In the 73 patients in the palliative group (median [range] age, 63 [45-82] years; 63 [86.0%] male), 71 (97.3%) had disease relapse and 68 (93.2%) died. Detectable pre-CT NFE2L2 alterations were independently associated with PFS (HR, 2.99; 95% CI, 1.35-6.61; P = .007) and OS (HR, 28.39; 95% CI, 7.26-111.03; P = 1.52 × 106), whereas high ctDNA levels (HR, 2.41; 95% CI, 1.18-4.95; P = .02) and alterations in pre–cycle III ctDNA (HR, 1.99; 95% CI, 1.03-3.85; P = .04) showed weaker associations with PFS. Alterations in pre-CT ctDNA were independently associated with OS (HR, 4.46; 95% CI, 1.86-10.69; P = 7.97 × 104).

Conclusions and Relevance  The findings of this cohort study indicate that prognostic models incorporating ctDNA features are useful in ESCC. Both ctDNA level and NFE2L2 alterations pre-CT and before cycle III were found to be important prognostic factors in palliative groups, and ctDNA alterations after treatment and at 6 months after surgery may define high-risk groups for recurrence in the curative group. High-risk patients can benefit by a timely switch to the next therapeutic options.


Persistent Identifierhttp://hdl.handle.net/10722/333995
ISSN
2023 Impact Factor: 15.7
2023 SCImago Journal Rankings: 3.905

 

DC FieldValueLanguage
dc.contributor.authorNg, HY-
dc.contributor.authorKo, JMY-
dc.contributor.authorLam, KO-
dc.contributor.authorKwong, DLW-
dc.contributor.authorLo, AWI-
dc.contributor.authorWong, IYH-
dc.contributor.authorWong, CLY-
dc.contributor.authorChan, SY-
dc.contributor.authorChan, KK-
dc.contributor.authorLaw, TT-
dc.contributor.authorDai, W-
dc.contributor.authorFong, HCH-
dc.contributor.authorChoy, FSF-
dc.contributor.authorLo, CK-
dc.contributor.authorChen, C-
dc.contributor.authorLaw, SYK-
dc.contributor.authorLung, ML-
dc.date.accessioned2023-10-10T09:42:26Z-
dc.date.available2023-10-10T09:42:26Z-
dc.date.issued2023-09-20-
dc.identifier.citationJAMA Surgery, 2023-
dc.identifier.issn2168-6254-
dc.identifier.urihttp://hdl.handle.net/10722/333995-
dc.description.abstract<p><strong>Importance</strong>  Esophageal squamous cell carcinoma (ESCC) is a deadly disease with frequent recurrence. There are unmet needs for prognostic biomarkers for dynamically monitoring disease progression and detecting minimal residual disease.</p><p><strong>Objective</strong>  To examine whether circulating tumor DNA is clinically useful as a prognostic biomarker for ESCC recurrence and patient survival.</p><p><strong>Design, Setting, and Participants</strong>  This single-center, population-based cohort study consecutively enrolled 147 patients receiving curative (n = 74) or palliative (n = 73) treatment at the surgery and clinical oncology departments of Queen Mary Hospital in Hong Kong from August 1, 2016, to September 31, 2021. Patients were followed up for 2 years. Plasma samples were collected at different longitudinal time points for a prospective circulating tumor DNA (ctDNA) next-generation sequencing profiling study of 77 actionable genes.</p><p><strong>Intervention</strong>  Patients were treated with up-front surgery, neoadjuvant chemoradiotherapy plus surgery with or without adjuvant therapy, or palliative chemotherapy (CT).</p><p><strong>Main Outcomes and Measures</strong>  Detection of circulating tumor DNA (ctDNA), progression-free survival (PFS), and overall survival (OS).</p><p><strong>Results</strong>  A total of 478 serial plasma samples from 147 patients with locoregional or metastatic ESCC were prospectively analyzed. Among the 74 patients in the curative group (median [range] age, 66 [46-85] years; 56 [76.0%] male), 44 (59.5%) relapsed and 36 (48.6%) died. For patients receiving curative surgical treatment, a high ctDNA level (hazard ratio [HR], 7.84; 95% CI, 1.87-32.97; <em>P</em> = .005) and ctDNA alterations (HR, 5.71; 95% CI, 1.81-17.97; <em>P</em> = .003) at 6 months postoperation were independently associated with poor OS. Among patients receiving neoadjuvant chemoradiotherapy, postneoadjuvant ctDNA alterations were associated with poor PFS (HR, 3.16; 95% CI, 1.17-8.52; <em>P</em> = .02). In the 73 patients in the palliative group (median [range] age, 63 [45-82] years; 63 [86.0%] male), 71 (97.3%) had disease relapse and 68 (93.2%) died. Detectable pre-CT <em>NFE2L2</em> alterations were independently associated with PFS (HR, 2.99; 95% CI, 1.35-6.61; <em>P</em> = .007) and OS (HR, 28.39; 95% CI, 7.26-111.03; <em>P</em> = 1.52 × 10<sup>−</sup><sup>6</sup>), whereas high ctDNA levels (HR, 2.41; 95% CI, 1.18-4.95; <em>P</em> = .02) and alterations in pre–cycle III ctDNA (HR, 1.99; 95% CI, 1.03-3.85; <em>P</em> = .04) showed weaker associations with PFS. Alterations in pre-CT ctDNA were independently associated with OS (HR, 4.46; 95% CI, 1.86-10.69; <em>P</em> = 7.97 × 10<sup>−</sup><sup>4</sup>).</p><p><strong>Conclusions and Relevance</strong>  The findings of this cohort study indicate that prognostic models incorporating ctDNA features are useful in ESCC. Both ctDNA level and <em>NFE2L2</em> alterations pre-CT and before cycle III were found to be important prognostic factors in palliative groups, and ctDNA alterations after treatment and at 6 months after surgery may define high-risk groups for recurrence in the curative group. High-risk patients can benefit by a timely switch to the next therapeutic options.</p>-
dc.languageeng-
dc.publisherAmerican Medical Association-
dc.relation.ispartofJAMA Surgery-
dc.titleCirculating Tumor DNA Dynamics as Prognostic Markers in Locally Advanced and Metastatic Esophageal Squamous Cell Carcinoma-
dc.typeArticle-
dc.identifier.doi10.1001/jamasurg.2023.4395-
dc.identifier.eissn2168-6262-
dc.identifier.issnl2168-6254-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats