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 whomn= 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.
引言：循环肿瘤DNA（ctDNA）作为一种有前景的无创诊断与监测生物标志物，在实体器官恶性肿瘤领域日益受到关注。然而，其在原发性及继发性肝癌患者肝移植（LT）前后的应用价值尚未得到充分探索。方法：本研究纳入了因肝细胞癌（HCC）、胆管癌（CCA）和结直肠癌肝转移（CRLM）接受肝移植并进行ctDNA检测的患者。在2019年11月至2023年9月期间，使用Guardant360、Guardant Reveal和Guardant360 CDx检测平台，对患者进行了移植前、移植后或两者兼具（序贯）的ctDNA检测。结果：研究共纳入21例患者，包括HCC（9例，43%）、CRLM（8例，38%）、CCA（3例，14%）以及混合型HCC/CCA（1例，5%）。中位随访时间为15个月（范围：1–124个月）。从术前检测到手术的中位时间为3个月（四分位距[IQR]：1–4；范围：0–5），从手术到术后检测的中位时间为9个月（IQR：2–22；范围：0.4–112）。共有13例（62%）患者接受了移植前检测，其中8例（62%）检测到ctDNA（ctDNA+），5例（32%）未检测到ctDNA（ctDNA-）。共有18例（86%）患者接受了移植后检测，其中11例（61%）为ctDNA+，7例（33%）为ctDNA-。在移植后检测中，ctDNA+患者的绝对复发率为50%（5例），而ctDNA-患者为25%（1例），但该差异无统计学意义（p=0.367）。共有6例（29%）患者（HCC=3例，CCA=1例，CRLM=2例）出现复发，中位无复发生存期为14个月（IQR：6–40）。其中4例患者在复发诊断后采集的移植后ctDNA检测呈阳性，而1例患者在复发前采集的移植后ctDNA检测呈阳性。共有10例（48%）患者接受了序贯ctDNA检测，其中5例（50%）实现了ctDNA清除（+/-）。其余患者分别为ctDNA持续阳性（+/+，3例，30%）、持续阴性（-/-，1例，10%）以及由阴转阳（-/+，1例，11%）。3例（30%）患者在移植后出现新的基因组改变，但均未复发。总体而言，中位肿瘤突变负荷（TMB）从移植前的1.23 mut/Mb降至移植后的0.00 mut/Mb。结论：ctDNA阳性患者的复发率高于ctDNA阴性患者，这表明ctDNA在预测根治性移植后复发方面具有潜在作用。基于序贯检测结果，肝移植具有清除ctDNA的潜力，证明了其在治疗全身性疾病方面的能力。移植医疗提供者应关注供体来源的游离DNA可能带来的影响，并需采取改进方法以应对此类问题。
肿瘤(癌症)患者之家