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Comparative assessment of standard and immune response criteria for evaluation of response to PD-1 monotherapy in unresectable HCC

  • Hepatobiliary
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Abdominal Radiology Aims and scope Submit manuscript

Abstract

Purpose

To assess response to programmed death-1 (PD-1) monotherapy (nivolumab) in hepatocellular carcinoma (HCC) patients using RECIST1.1, modified RECIST (mRECIST), and immune RECIST (iRECIST). A secondary objective was to identify clinicolaboratory and imaging variables predictive of progressive disease (PD) and overall survival (OS).

Methods

Patients with HCC treated with nivolumab at a single institution from 5/2016 to 12/2019 with MRI or CT performed ≥ 4 weeks post treatment were retrospectively assessed. Patients who received concurrent locoregional, radiation, or other systemic therapies were excluded. Response was assessed by 2 observers in consensus using RECIST1.1, mRECIST, and iRECIST at 3/6/9/12-month time points. Time to progression (TTP) and OS were recorded. Clinicolaboratory and imaging variables were evaluated as predictors of PD and OS using uni-/multivariable and Cox regression analyses.

Results

Fifty-eight patients (42M/16F) were included. 118 target lesions (TL) were identified before treatment. Baseline mean TL size was 49.1 ± 43.5 mm (range 10–189 mm) for RECIST1.1/iRECIST and 46.3 ± 42.3 mm (range 10–189 mm) for mRECIST. Objective response rate (ORR) was 21% for mRECIST/iRECIST/RECIST1.1, with no cases of pseudoprogression. Median OS and median TTP were 717 days and 127 days for RECIST1.1/mRECIST/iRECIST-iUPD (unconfirmed PD). Older age, MELD/Child–Pugh scores, AFP, prior transarterial radioembolization (TARE), and larger TL size were predictive of PD and/or poor OS using mRECIST/iRECIST. The strongest predictor of PD (HR = 2.49, 95% CI 1.29–4.81, p = 0.007) was TARE. The strongest predictor of poor OS was PD by mRECIST/iRECIST at 3 months (HR = 2.26, 95% CI 1.00–5.10, p = 0.05) with borderline significance.

Conclusion

Our results show ORR of 21%, equivalent for mRECIST, iRECIST, and RECIST1.1 in patients with advanced HCC clinically treated with nivolumab.

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Data availability

Upon request, the authors are prepared to send relevant documentation or data in order to verify the validity of the results presented. Code availability (software application or custom code): N/A.

Code availability

N/A.

Abbreviations

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

CP:

Child–Pugh

CR:

Complete response

CT:

Computed tomography

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

INR:

International normalized ratio

iCPD:

Confirmed progressive disease

iRECIST:

Immune Response Evaluation Criteria in Solid Tumors

iUPD:

Unconfirmed progressive disease

LRT:

Locoregional therapy

MELD:

Model for end-stage liver disease

mRECIST:

Modified Response Evaluation Criteria in Solid Tumors

MRI:

Magnetic resonance imaging

ORR:

Objective response rate

OS:

Overall survival

PD-1:

Programmed death-1

PD:

Progressive disease

PR:

Partial response

RECIST1.1:

Response Evaluation Criteria in Solid Tumors

SD:

Stable disease

TL:

Target lesion

TARE:

Transarterial radioembolization

TTP:

Time to progression

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Authors and Affiliations

  1. Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, Box 1234, New York, NY, 10029, USA

    Sara Lewis, Mario A. Cedillo, Karen M. Lee, Darrell V. Morris & Bachir Taouli

  2. BioMedical Engineering and Imaging Institute, Icahn School of Medicine Mount Sinai, New York, NY, USA

    Sara Lewis, Octavia Bane, Stefanie Hectors, Daniel Stocker & Bachir Taouli

  3. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Weiping Ma & Pei Wang

  4. Department of Surgery and Cancer, Imperial College, London, UK

    David Pinato

  5. Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Max Sung, Thomas Marron & Myron Schwartz

  6. The neoAdjuvant Research Group to Evaluate Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Thomas Marron

  7. Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Thomas Marron

  8. Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Max Sung & Thomas Marron

  9. Liver Cancer Program, Division of Liver Diseases and RM Transplant Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Thomas Marron, Myron Schwartz & Bachir Taouli

  10. Department of Surgery, Recanati/Miller Transplantation Institute, Icahn School of Medicine Mount Sinai, New York, NY, USA

    Myron Schwartz

Authors
  1. Sara Lewis
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  2. Mario A. Cedillo
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Contributions

SL: Conceptualization; data curation; formal analysis; investigation; methodology; project administration; supervision; and writing. MAC: data curation; formal analysis; and project administration. KML: data curation; formal analysis; and investigation. OB: conceptualization and methodology. SJH: conceptualization; methodology; and writing. WM: formal analysis; methodology; and software. PW: formal analysis; investigation; and supervision. DS: conceptualization; formal analysis; and methodology. DM: data curation; project administration; and writing. DJP, MS, and TM: supervision and writing. MS: data curation; supervision; and writing. BT: conceptualization; supervision; visualization; and writing.

Corresponding author

Correspondence to Sara Lewis.

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Conflict of interest

Stefanie Hectors: Employment at Regeneron Pharmaceuticals. David Pinato: Lecture fees (ViiV Healthcare, EISAI, BMS, Roche, Bayer Healthcare), travel expenses (BMS, MSD and Bayer Healthcare), consulting fees (Mina Therapeutics, EISAI, Roche, Astra Zeneca, DaVolterra) research funding to institution (MSD, BMS, Biognosys). Thomas Marron: Advisory boards and/or DSMBs (Boehringer Ingelheim, BMS, AstraZeneca, Genentech, Celldex, and Regeneron), research grant support (BMS, Regeneron and Boehringer Ingelheim). Bachir Taouli: Grant/research support (Bayer, Takeda, Regeneron, Siemens, Echosens). The remaining authors (SL, MAC, KML, OB, WM, PW, DS, DVM, MS, and MS) have no relevant disclosures.

Ethical approval

Because this work involves the use of human subjects, we ensure that all procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. The study was approved by the Institutions Review Board at the ISMMS.

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Lewis, S., Cedillo, M.A., Lee, K.M. et al. Comparative assessment of standard and immune response criteria for evaluation of response to PD-1 monotherapy in unresectable HCC. Abdom Radiol 47, 969–980 (2022). https://doi.org/10.1007/s00261-021-03386-0

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  • DOI: https://doi.org/10.1007/s00261-021-03386-0

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