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HIFU for the treatment of difficult colorectal liver metastases with unsuitable indications for resection and radiofrequency ablation: a phase I clinical trial

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Abstract

Background

The goal of this study is to evaluate the safety and efficacy of high intensity focused ultrasound (HIFU) for patients with colorectal liver metastases (CRLM) but were contraindicated for resection and radiofrequency ablation.

Methods

Patients between 20 and 80 years of age with 1–3 liver metastases from colorectal cancer were selected. Included patients have had their primary lesions removed with no evidence of extrahepatic metastasis prior to the study. Ultrasound-guided HIFU was employed and target regions’ ablation was achieved with repeated sonications from the deep to shallow regions of the tumors section by section.

Results

Thirteen patients were enrolled. The most common adverse events (AEs) were pain (n = 8), followed by fatigue (n = 7), increased aspartate aminotransferase (AST) (n = 7), increased alanine aminotransferase (ALT) (n = 5), and skin edema (n = 4). No grade ≥ 3 AEs occurred and while most patients (76.9%) achieved a complete response, three patients achieved a partial response. The objective response rate was 100% after the first HIFU treatment. Nine patients relapsed but the tumors were mostly isolated to the liver (8/9). The median follow-up period was 25 months. The 2-year progression-free survival (PFS) was 16.7%, and the median PFS was 9 months. Notably, the 2-year overall survival (OS) was 77.8%, and the median OS was 25 months.

Conclusion

This study indicates that the HIFU treatment is safe, is able to achieve a good tumor response rate and long-term prognosis even when the foci were in high-risk locations, and should be considered for patients who were considered unsuitable for other local treatments.

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Abbreviations

CRLM:

Colorectal liver metastases

OS:

Overall survival

PFS:

Progression-free survival

RFA:

Radiofrequency ablation

MWA:

Microwave ablation

CTCAE:

Common terminology criteria for adverse events

AEs:

Adverse events

CR:

Complete response

PR:

Partial response

SD:

Stable disease

ORR:

Objective response rate

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Funding

Funding was provided by the Medical Health Science and Technology Project of Zhejiang Provincial Health Commission (2018KY699) and the Medical Health Science and Technology Project of Zhejiang Provincial Health Commission (2017KY138).

Author information

Authors and Affiliations

  1. Department of Tumor HIFU Therapy, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China

    Tong Yang, Ning He & Zhi Zheng

  2. Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Haishu District, Northwest Street 41, Ningbo, 315010, Zhejiang, China

    Tong Yang & Lihu Gu

  3. Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Haishu District, Northwest Street 41, Ningbo, 315010, Zhejiang, China

    Lihu Gu

  4. Medical College of Ningbo University, Ningbo, China

    Derry Minyao Ng

  5. The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China

    Nannan Du

  6. Department of Anus and Intestine Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China

    Xiaoyu Dai & Mingjun Dong

  7. Department of General Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Haishu District, Northwest Street 41, Ningbo, 315010, Zhejiang, China

    Ping Chen, Feng Wu, Xinfeng Zhou & Lihu Gu

  8. Department of Medical Image, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China

    Bo Chen & Kun Yan

  9. Department of Interventional Therapy, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China

    Xiaoxiang Fan

Authors
  1. Tong Yang
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  2. Derry Minyao Ng
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  4. Ning He
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  7. Feng Wu
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  8. Bo Chen
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  9. Xiaoxiang Fan
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  10. Kun Yan
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  11. Xinfeng Zhou
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  12. Mingjun Dong
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  13. Zhi Zheng
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  14. Lihu Gu
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Contributions

Design of the study: LG and TY. Data management and analyses: TY, NH, XD, PC, FW, BC, XF, KY, and ZZ. Writing and revising the manuscript: DMN, ND, XZ, and MD. All authors contributed toward data analysis, drafting and critically revising the paper and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Lihu Gu.

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Disclosures

The author Tong Yang, Derry Minyao Ng, Nannan Du, Ning He, Xiaoyu Dai, Ping Chen, Feng Wu, Bo Chen, Xiaoxiang Fan, Kun Yan, Xinfeng Zhou, Mingjun Dong, Zhi Zheng, and Lihu Gu have no conflict of interest or financial ties to disclose. There are no corporate or commercial relationships that might pose a conflict of interest. There are no author’s relationships with pharmaceutical or device companies to disclose.

Ethical approval

This study was approved by the Ethics Committee of the HwaMei Hospital, University of Chinese Academy of Sciences (approval NO.PJ-NBEY-KY-2019-071-01). The study was registered with Chictr.org (ChiCTR1900024259).

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Supplement Table 1. Detail of 17 lesions for 13 patients. Supplementary file1 (DOC 14 kb)

464_2020_7644_MOESM2_ESM.tif

Supplement Figure 1. MRI of HIFU treatment for colorectal liver metastases (CRLM), A: before the treatment, B: after the treatment.Supplementary file2 (TIF 1948 kb)

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Yang, T., Ng, D.M., Du, N. et al. HIFU for the treatment of difficult colorectal liver metastases with unsuitable indications for resection and radiofrequency ablation: a phase I clinical trial. Surg Endosc 35, 2306–2315 (2021). https://doi.org/10.1007/s00464-020-07644-y

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  • DOI: https://doi.org/10.1007/s00464-020-07644-y

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