Liver Transplant as a Treatment of Primary and Secondary Liver Neoplasms

Gorji, Leva; Brown, Zachary J.; Limkemann, Ashley; Schenk, Austin D.; Pawlik, Timothy M.

doi:10.1001/jamasurg.2023.6083

Cited by 3 publications

(2 citation statements)

References 78 publications

(170 reference statements)

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“…Liver transplant as a treatment for primary and secondary liver malignancy has grown in volume, with expansion from HCC to CCA and, more recently, to CRLM [ 6 ]. However, recurrence after LT remains a concern [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…Liver transplant is the only curative-intent treatment option for patients with unresectable hepatocellular carcinoma, cholangiocarcinoma, and colorectal liver metastasis [ 1 , 2 , 3 , 4 , 5 , 6 ]. However, the recurrence rates may be as high as 20–50% in certain conditions, highlighting the need for thorough and frequent post-transplant monitoring [ 3 , 4 , 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Circulating Tumor DNA Profiling in Liver Transplant for Hepatocellular Carcinoma, Cholangiocarcinoma, and Colorectal Liver Metastases: A Programmatic Proof of Concept

Hong,

Wehrle,

Zhang

et al. 2024

Cancers

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Introduction: Circulating tumor DNA (ctDNA) is emerging as a promising, non-invasive diagnostic and surveillance biomarker in solid organ malignancy. However, its utility before and after liver transplant (LT) for patients with primary and secondary liver cancers is still underexplored. Methods: Patients undergoing LT for hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and colorectal liver metastases (CRLM) with ctDNA testing were included. CtDNA testing was conducted pre-transplant, post-transplant, or both (sequential) from 11/2019 to 09/2023 using Guardant360, Guardant Reveal, and Guardant360 CDx. Results: 21 patients with HCC (n = 9, 43%), CRLM (n = 8, 38%), CCA (n = 3, 14%), and mixed HCC/CCA (n = 1, 5%) were included in the study. The median follow-up time was 15 months (range: 1–124). The median time from pre-operative testing to surgery was 3 months (IQR: 1–4; range: 0–5), and from surgery to post-operative testing, it was 9 months (IQR: 2–22; range: 0.4–112). A total of 13 (62%) patients had pre-transplant testing, with 8 (62%) having ctDNA detected (ctDNA+) and 5 (32%) not having ctDNA detected (ctDNA-). A total of 18 (86%) patients had post-transplant testing, 11 (61%) of whom were ctDNA+ and 7 (33%) of whom were ctDNA-. The absolute recurrence rates were 50% (n = 5) in those who were ctDNA+ vs. 25% (n = 1) in those who were ctDNA- in the post-transplant setting, though this difference was not statistically significant (p = 0.367). Six (29%) patients (HCC = 3, CCA = 1, CRLM = 2) experienced recurrence with a median recurrence-free survival of 14 (IQR: 6–40) months. Four of these patients had positive post-transplant ctDNA collected following diagnosis of recurrence, while one patient had positive post-transplant ctDNA collected preceding recurrence. A total of 10 (48%) patients had sequential ctDNA testing, of whom n = 5 (50%) achieved ctDNA clearance (+/−). The remainder were ctDNA+/+ (n = 3, 30%), ctDNA−/− (n = 1, 10%), and ctDNA−/+ (n = 1, 11%). Three (30%) patients showed the acquisition of new genomic alterations following transplant, all without recurrence. Overall, the median tumor mutation burden (TMB) decreased from 1.23 mut/Mb pre-transplant to 0.00 mut/Mb post-transplant. Conclusions: Patients with ctDNA positivity experienced recurrence at a higher rate than the ctDNA- patients, indicating the potential role of ctDNA in predicting recurrence after curative-intent transplant. Based on sequential testing, LT has the potential to clear ctDNA, demonstrating the capability of LT in the treatment of systemic disease. Transplant providers should be aware of the potential of donor-derived cell-free DNA and improved approaches are necessary to address such concerns.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Circulating Tumor DNA Profiling in Liver Transplant for Hepatocellular Carcinoma, Cholangiocarcinoma, and Colorectal Liver Metastases: A Programmatic Proof of Concept

Hong,

Wehrle,

Zhang

et al. 2024

Cancers

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Outcomes of liver transplant for colorectal liver metastasis: a systematic review and meta-analysis

Dawood,

Brown,

Munir

et al. 2024

Journal of Gastrointestinal Surgery

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Artificial intelligence and liver transplantation: looking inside the Pandora’s box

Sepulveda,

Pravisani

2024

Art Int Surg

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Artificial intelligence (AI) is the discipline of computer science dedicated to processing a large amount of throughput data and is based on algorithms that can rationalize increasingly complex tasks and ultimately reproduce human intelligence. It has been speculated for clinical uses in liver transplantation (LT) for several years, but its application remains incipient worldwide. Therefore, the recent advancements of digital and robotic tools in daily medical practice make the modern environment propitious to its proper implementation. Nevertheless, it is noteworthy that this technology has significant limitations: (i) its unconditional dependence on a pre-established reliable and extensive database; (ii) the potential impact on independent medical decision-making; and (iii) a major economic and environmental burden. So, despite its seducing and flawless simplicity features, AI emerges as a new “Pandora’s box” that should be carefully understood and used under the light of ethical principles to improve clinical outcomes, promote medical and para-medical working conditions, and increase patient safety and access to medical care. The present work aims to review literature data supporting AI implementation on this basis.

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Liver Transplant as a Treatment of Primary and Secondary Liver Neoplasms

Cited by 3 publications

References 78 publications

Circulating Tumor DNA Profiling in Liver Transplant for Hepatocellular Carcinoma, Cholangiocarcinoma, and Colorectal Liver Metastases: A Programmatic Proof of Concept

Circulating Tumor DNA Profiling in Liver Transplant for Hepatocellular Carcinoma, Cholangiocarcinoma, and Colorectal Liver Metastases: A Programmatic Proof of Concept

Outcomes of liver transplant for colorectal liver metastasis: a systematic review and meta-analysis

Artificial intelligence and liver transplantation: looking inside the Pandora’s box

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