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Erschienen in: Journal of Cancer Research and Clinical Oncology 8/2022

30.08.2021 | Original Article – Clinical Oncology

Role of the alpha-fetoprotein response in immune checkpoint inhibitor-based treatment of patients with hepatocellular carcinoma

verfasst von: Ha Il Kim, Jihye Lim, Ju Hyun Shim

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 8/2022

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Abstract

Purpose

The dynamics of serum alpha-fetoprotein (AFP) level have been found to be a useful predictor of therapeutic responsiveness in patients with hepatocellular carcinoma (HCC). We evaluated whether AFP changes were able to accurately reflect imaging-based responses and predict prognosis in patients receiving therapies including immune-checkpoint inhibitors (ICIs).

Methods

A total of 108 HCC patients with baseline serum AFP ≥ 20 ng/mL who received ICI-based treatment were included. We evaluated AFP-based responses, coupled with radiographic responses by RECIST, at 6–10 (time-point 1, TP1) and 14–18 weeks (time-point 2, TP2) of therapy in terms of the change of AFP from baseline, with a > 20% decrease or increase in level corresponding to the AFP response and progression, respectively. We examined the correlations between AFP and imaging-based responses, and the prognostic implications of the AFP-based measure.

Results

Based on AFP change, there were 24 and 20 responders and 74 and 24 progressors at TP1 and TP2, respectively. The AFP responders yielded radiological objective responses in 90.9% (10/11) and 93.8% (15/16) of the cases at TP1 and TP2, respectively, compared with only 1.4% and none, respectively, of the AFP progressors at the corresponding times. The agreement between progression by RECIST and increased AFP level at the two time-points was 93.8% and 95.0%, respectively. The accuracy of the AFP-based criterion for predicting radiologic response/progression was comparable at TP1 and TP2. Both “AFP responder” and “AFP progressor” at TP1 or TP2 independently predicted the overall survival of patients (adjusted hazard ratios [95% confidence intervals], 0.360 [0.174–0.743] and 0.315 [0.117–0.850]; and 2.525 [1.362–4.679] and 3.908 [1.563–9.769], respectively).

Conclusion

Our study suggests that on-treatment AFP changes can complement imaging findings and provide prognostic information for evaluating patients with AFP-producing HCC treated with ICI-based regimens.
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Literatur
Zurück zum Zitat Borcoman E, Kanjanapan Y, Champiat S, Kato S, Servois V, Kurzrock R et al (2019) Novel patterns of response under immunotherapy. Ann Oncol 30(3):385–396CrossRef Borcoman E, Kanjanapan Y, Champiat S, Kato S, Servois V, Kurzrock R et al (2019) Novel patterns of response under immunotherapy. Ann Oncol 30(3):385–396CrossRef
Zurück zum Zitat Brenner DJ, Eric J, Hall DP (2007) Computed tomography—an increasing source of radiation exposure. N Engl J Med 357:2277–2284CrossRef Brenner DJ, Eric J, Hall DP (2007) Computed tomography—an increasing source of radiation exposure. N Engl J Med 357:2277–2284CrossRef
Zurück zum Zitat Champiat S, Dercle L, Ammari S, Massard C, Hollebecque A, Postel-Vinay S et al (2017) Hyperprogressive disease is a new pattern of progression in cancer patients treated by anti-PD-1/PD-L1. Clin Cancer Res 23(8):1920–1928CrossRef Champiat S, Dercle L, Ammari S, Massard C, Hollebecque A, Postel-Vinay S et al (2017) Hyperprogressive disease is a new pattern of progression in cancer patients treated by anti-PD-1/PD-L1. Clin Cancer Res 23(8):1920–1928CrossRef
Zurück zum Zitat Chan SL (2020) Hyperprogression in hepatocellular carcinoma: illusion or reality? J Hepatol 74:269–271CrossRef Chan SL (2020) Hyperprogression in hepatocellular carcinoma: illusion or reality? J Hepatol 74:269–271CrossRef
Zurück zum Zitat Chan SL, Mo FK, Johnson PJ, Hui EP, Ma BB, Ho WM et al (2009) New utility of an old marker: serial alpha-fetoprotein measurement in predicting radiologic response and survival of patients with hepatocellular carcinoma undergoing systemic chemotherapy. J Clin Oncol 27(3):446–452CrossRef Chan SL, Mo FK, Johnson PJ, Hui EP, Ma BB, Ho WM et al (2009) New utility of an old marker: serial alpha-fetoprotein measurement in predicting radiologic response and survival of patients with hepatocellular carcinoma undergoing systemic chemotherapy. J Clin Oncol 27(3):446–452CrossRef
Zurück zum Zitat Cheng AL, Hsu C, Chan SL, Choo SP, Kudo M (2020) Challenges of combination therapy with immune checkpoint inhibitors for hepatocellular carcinoma. J Hepatol 72(2):307–319CrossRef Cheng AL, Hsu C, Chan SL, Choo SP, Kudo M (2020) Challenges of combination therapy with immune checkpoint inhibitors for hepatocellular carcinoma. J Hepatol 72(2):307–319CrossRef
Zurück zum Zitat Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247CrossRef Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247CrossRef
Zurück zum Zitat European Association for the Study of the Liver (2018) EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 69(1):182–236CrossRef European Association for the Study of the Liver (2018) EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 69(1):182–236CrossRef
Zurück zum Zitat Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY et al (2020) Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med 382(20):1894–1905CrossRef Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY et al (2020) Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med 382(20):1894–1905CrossRef
Zurück zum Zitat Fujiwara N, Tateishi R, Akahane M, Taguri M, Minami T, Mikami S et al (2013) Changes in risk of immediate adverse reactions to iodinated contrast media by repeated administrations in patients with hepatocellular carcinoma. PLoS ONE 8(10):e76018CrossRef Fujiwara N, Tateishi R, Akahane M, Taguri M, Minami T, Mikami S et al (2013) Changes in risk of immediate adverse reactions to iodinated contrast media by repeated administrations in patients with hepatocellular carcinoma. PLoS ONE 8(10):e76018CrossRef
Zurück zum Zitat Greten TF, Lai CW, Li G, Staveley-O’Carroll KF (2019) Targeted and immune-based therapies for hepatocellular carcinoma. Gastroenterology 156(2):510–524CrossRef Greten TF, Lai CW, Li G, Staveley-O’Carroll KF (2019) Targeted and immune-based therapies for hepatocellular carcinoma. Gastroenterology 156(2):510–524CrossRef
Zurück zum Zitat Guite KM, Hinshaw JL, Ranallo FN, Lindstrom MJ, Lee FT Jr (2011) Ionizing radiation in abdominal CT: unindicated multiphase scans are an important source of medically unnecessary exposure. J Am Coll Radiol 8(11):756–761CrossRef Guite KM, Hinshaw JL, Ranallo FN, Lindstrom MJ, Lee FT Jr (2011) Ionizing radiation in abdominal CT: unindicated multiphase scans are an important source of medically unnecessary exposure. J Am Coll Radiol 8(11):756–761CrossRef
Zurück zum Zitat Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR et al (2018) AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 67(1):358–380CrossRef Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR et al (2018) AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 67(1):358–380CrossRef
Zurück zum Zitat Kang H, Lee HY, Lee KS, Kim JH (2012) Imaging-based tumor treatment response evaluation: review of conventional, new, and emerging concepts. Korean J Radiol 13(4):371–390CrossRef Kang H, Lee HY, Lee KS, Kim JH (2012) Imaging-based tumor treatment response evaluation: review of conventional, new, and emerging concepts. Korean J Radiol 13(4):371–390CrossRef
Zurück zum Zitat Kelley RK, Meyer T, Rimassa L, Merle P, Park JW, Yau T et al (2020) Serum alpha-fetoprotein levels and clinical outcomes in the phase III CELESTIAL study of cabozantinib versus placebo in patients with advanced hepatocellular carcinoma. Clin Cancer Res 26(18):4795–4804CrossRef Kelley RK, Meyer T, Rimassa L, Merle P, Park JW, Yau T et al (2020) Serum alpha-fetoprotein levels and clinical outcomes in the phase III CELESTIAL study of cabozantinib versus placebo in patients with advanced hepatocellular carcinoma. Clin Cancer Res 26(18):4795–4804CrossRef
Zurück zum Zitat Kim CG, Kim C, Yoon SE, Kim KH, Choi SJ, Kang B et al (2021) Hyperprogressive disease during PD-1 blockade in patients with advanced hepatocellular carcinoma. J Hepatol 74(2):350–359CrossRef Kim CG, Kim C, Yoon SE, Kim KH, Choi SJ, Kang B et al (2021) Hyperprogressive disease during PD-1 blockade in patients with advanced hepatocellular carcinoma. J Hepatol 74(2):350–359CrossRef
Zurück zum Zitat Korean Liver Cancer Association-National Cancer Center (2019) Korean Liver Cancer Association-National Cancer Center Korea Practice guidelines for the management of hepatocellular carcinoma. Gut Liver 13(3):227–299 CrossRef Korean Liver Cancer Association-National Cancer Center (2019) Korean Liver Cancer Association-National Cancer Center Korea Practice guidelines for the management of hepatocellular carcinoma. Gut Liver 13(3):227–299 CrossRef
Zurück zum Zitat Koulakian H, Allaham W, Vilgrain V, Ronot M (2019) Non-measurable infiltrative HCC: is post-contrast attenuation on CT a sign of tumor response? Eur Radiol 29(8):4389–4399CrossRef Koulakian H, Allaham W, Vilgrain V, Ronot M (2019) Non-measurable infiltrative HCC: is post-contrast attenuation on CT a sign of tumor response? Eur Radiol 29(8):4389–4399CrossRef
Zurück zum Zitat Lee PC, Chao Y, Chen MH, Lan KH, Lee CJ, Lee IC et al (2020) Predictors of response and survival in immune checkpoint inhibitor-treated unresectable hepatocellular carcinoma. Cancers (basel) 12(1):182CrossRef Lee PC, Chao Y, Chen MH, Lan KH, Lee CJ, Lee IC et al (2020) Predictors of response and survival in immune checkpoint inhibitor-treated unresectable hepatocellular carcinoma. Cancers (basel) 12(1):182CrossRef
Zurück zum Zitat Lee MS, Ryoo B-Y, Hsu C-H, Numata K, Stein S, Verret W et al (2020) Atezolizumab with or without bevacizumab in unresectable hepatocellular carcinoma (GO30140): an open-label, multicentre, phase 1b study. Lancet Oncol 21(6):808–820CrossRef Lee MS, Ryoo B-Y, Hsu C-H, Numata K, Stein S, Verret W et al (2020) Atezolizumab with or without bevacizumab in unresectable hepatocellular carcinoma (GO30140): an open-label, multicentre, phase 1b study. Lancet Oncol 21(6):808–820CrossRef
Zurück zum Zitat Lee KH, Lee S, Park JH, Lee SS, Kim HY, Lee WJ et al (2021) Risk of hematologic malignant neoplasms from abdominopelvic computed tomographic radiation in patients who underwent appendectomy. JAMA Surg 156:343–351CrossRef Lee KH, Lee S, Park JH, Lee SS, Kim HY, Lee WJ et al (2021) Risk of hematologic malignant neoplasms from abdominopelvic computed tomographic radiation in patients who underwent appendectomy. JAMA Surg 156:343–351CrossRef
Zurück zum Zitat Lencioni R, Llovet JM (2010) Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 30(1):52–60CrossRef Lencioni R, Llovet JM (2010) Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 30(1):52–60CrossRef
Zurück zum Zitat Nishino M (2018) Tumor response assessment for precision cancer therapy: response evaluation on criteria in solid tumors and beyond. ASCO 38:1019–1029 Nishino M (2018) Tumor response assessment for precision cancer therapy: response evaluation on criteria in solid tumors and beyond. ASCO 38:1019–1029
Zurück zum Zitat Omata M, Cheng AL, Kokudo N, Kudo M, Lee JM, Jia J et al (2017) Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int 11(4):317–370CrossRef Omata M, Cheng AL, Kokudo N, Kudo M, Lee JM, Jia J et al (2017) Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int 11(4):317–370CrossRef
Zurück zum Zitat Personeni N, Bozzarelli S, Pressiani T, Rimassa L, Tronconi MC, Sclafani F et al (2012) Usefulness of alpha-fetoprotein response in patients treated with sorafenib for advanced hepatocellular carcinoma. J Hepatol 57(1):101–107CrossRef Personeni N, Bozzarelli S, Pressiani T, Rimassa L, Tronconi MC, Sclafani F et al (2012) Usefulness of alpha-fetoprotein response in patients treated with sorafenib for advanced hepatocellular carcinoma. J Hepatol 57(1):101–107CrossRef
Zurück zum Zitat Riaz A, Ryu RK, Kulik LM, Mulcahy MF, Lewandowski RJ, Minocha J et al (2009) Alpha-fetoprotein response after locoregional therapy for hepatocellular carcinoma: oncologic marker of radiologic response, progression, and survival. J Clin Oncol 27(34):5734–5742CrossRef Riaz A, Ryu RK, Kulik LM, Mulcahy MF, Lewandowski RJ, Minocha J et al (2009) Alpha-fetoprotein response after locoregional therapy for hepatocellular carcinoma: oncologic marker of radiologic response, progression, and survival. J Clin Oncol 27(34):5734–5742CrossRef
Zurück zum Zitat Rimola J, Da Fonseca LG, Sapena V, Perello C, Guerrero A, Simo MT et al (2020) Radiological response to nivolumab in patients with hepatocellular carcinoma: a multicenter analysis of real-life practice. Eur J Radiol 135:109484CrossRef Rimola J, Da Fonseca LG, Sapena V, Perello C, Guerrero A, Simo MT et al (2020) Radiological response to nivolumab in patients with hepatocellular carcinoma: a multicenter analysis of real-life practice. Eur J Radiol 135:109484CrossRef
Zurück zum Zitat Robert C (2020) A decade of immune-checkpoint inhibitors in cancer therapy. Nat Commun 11(1):3801CrossRef Robert C (2020) A decade of immune-checkpoint inhibitors in cancer therapy. Nat Commun 11(1):3801CrossRef
Zurück zum Zitat Rustin GJ, Vergote I, Eisenhauer E, Pujade-Lauraine E, Quinn M, Thigpen T et al (2011) Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the Gynecological Cancer Intergroup (GCIG). Int J Gynecol Cancer 21(2):419–423CrossRef Rustin GJ, Vergote I, Eisenhauer E, Pujade-Lauraine E, Quinn M, Thigpen T et al (2011) Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the Gynecological Cancer Intergroup (GCIG). Int J Gynecol Cancer 21(2):419–423CrossRef
Zurück zum Zitat Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA et al (2008) Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol 26(7):1148–1159CrossRef Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA et al (2008) Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol 26(7):1148–1159CrossRef
Zurück zum Zitat Schoenfeld AJ, Hellmann MD (2020) Acquired resistance to immune checkpoint inhibitors. Cancer Cell 37(4):443–455CrossRef Schoenfeld AJ, Hellmann MD (2020) Acquired resistance to immune checkpoint inhibitors. Cancer Cell 37(4):443–455CrossRef
Zurück zum Zitat Seymour L, Bogaerts J, Perrone A, Ford R, Schwartz LH, Mandrekar S et al (2017) iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol 18(3):e143–e152CrossRef Seymour L, Bogaerts J, Perrone A, Ford R, Schwartz LH, Mandrekar S et al (2017) iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol 18(3):e143–e152CrossRef
Zurück zum Zitat Shao YY, Lin ZZ, Hsu C, Shen YC, Hsu CH, Cheng AL (2010) Early alpha-fetoprotein response predicts treatment efficacy of antiangiogenic systemic therapy in patients with advanced hepatocellular carcinoma. Cancer 116(19):4590–4596CrossRef Shao YY, Lin ZZ, Hsu C, Shen YC, Hsu CH, Cheng AL (2010) Early alpha-fetoprotein response predicts treatment efficacy of antiangiogenic systemic therapy in patients with advanced hepatocellular carcinoma. Cancer 116(19):4590–4596CrossRef
Zurück zum Zitat Shao YY, Liu TH, Hsu C, Lu LC, Shen YC, Lin ZZ et al (2019) Early alpha-foetoprotein response associated with treatment efficacy of immune checkpoint inhibitors for advanced hepatocellular carcinoma. Liver Int 39(11):2184–2189CrossRef Shao YY, Liu TH, Hsu C, Lu LC, Shen YC, Lin ZZ et al (2019) Early alpha-foetoprotein response associated with treatment efficacy of immune checkpoint inhibitors for advanced hepatocellular carcinoma. Liver Int 39(11):2184–2189CrossRef
Zurück zum Zitat Sosna J (2019) Is RECIST version 1.1 reliable for tumor response assessment in metastatic cancer? Radiology 290(2):357–358CrossRef Sosna J (2019) Is RECIST version 1.1 reliable for tumor response assessment in metastatic cancer? Radiology 290(2):357–358CrossRef
Zurück zum Zitat Suzuki C, Jacobsson H, Torkzad MR, Eriksson-Alm Y, Berg E, Kubo A et al (2008) Radiologic measurements of tumor response to treatment: practical approaches and limitations. RSNA 28:329–344 Suzuki C, Jacobsson H, Torkzad MR, Eriksson-Alm Y, Berg E, Kubo A et al (2008) Radiologic measurements of tumor response to treatment: practical approaches and limitations. RSNA 28:329–344
Zurück zum Zitat Tang J, Pearce L, O’Donnell-Tormey J, Hubbard-Lucey VM (2018) Trends in the global immuno-oncology landscape. Nat Rev Drug Discov 17(11):783–784CrossRef Tang J, Pearce L, O’Donnell-Tormey J, Hubbard-Lucey VM (2018) Trends in the global immuno-oncology landscape. Nat Rev Drug Discov 17(11):783–784CrossRef
Zurück zum Zitat Vora SR, Zheng H, Stadler ZK, Fuchs CS, Zhu AX (2009) Serum alpha-fetoprotein response as a surrogate for clinical outcome in patients receiving systemic therapy for advanced hepatocellular carcinoma. Oncologist 14(7):717–725CrossRef Vora SR, Zheng H, Stadler ZK, Fuchs CS, Zhu AX (2009) Serum alpha-fetoprotein response as a surrogate for clinical outcome in patients receiving systemic therapy for advanced hepatocellular carcinoma. Oncologist 14(7):717–725CrossRef
Zurück zum Zitat Yau T, Hsu C, Kim TY, Choo SP, Kang YK, Hou MM et al (2019) Nivolumab in advanced hepatocellular carcinoma: Sorafenib-experienced Asian cohort analysis. J Hepatol 71(3):543–552CrossRef Yau T, Hsu C, Kim TY, Choo SP, Kang YK, Hou MM et al (2019) Nivolumab in advanced hepatocellular carcinoma: Sorafenib-experienced Asian cohort analysis. J Hepatol 71(3):543–552CrossRef
Metadaten
Titel
Role of the alpha-fetoprotein response in immune checkpoint inhibitor-based treatment of patients with hepatocellular carcinoma
verfasst von
Ha Il Kim
Jihye Lim
Ju Hyun Shim
Publikationsdatum
30.08.2021
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 8/2022
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-021-03727-y

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