Research ArticleAlpha-fetoprotein response correlates with EASL response and survival in solitary hepatocellular carcinoma treated with transarterial therapies: A subgroup analysis
Introduction
The incidence of HCC is increasing [1]; it has tripled between 1975 and 2005 [2]. Most patients present at an advanced stage beyond curative therapies, with sorafenib prolonging survival in advanced HCC [3], [4]. LRTs play a palliative role by inducing tumor necrosis, delaying progression, and improving survival [5], [6], [7], [8], [9], [10], [11], [12], [13], [14]. Following HCC treatment, it is the clinical standard of care to follow patients with triphasic contrast-enhanced computerized tomography (CT) and magnetic resonance (MR) imaging. The utility of tumor markers to assess response, such as AFP, remains controversial.
AFP is the only universally recognized tumor marker for hepatocellular carcinoma. It has been investigated as a potential screening, diagnostic, and prognostic tool [15], [16], [17]. Several studies have reported the capability of AFP response in prognosticating response to therapy and survival outcomes. Riaz et al. demonstrated that AFP response to LRTs can be used for assessing tumor response, time-to-progression, and overall survival [18]. Such studies have also been reported with resection, chemotherapy, and radiofrequency ablation [19], [20], [21].
The observation of response to any treatment by imaging or AFP is time-dependent [22]. Since treatment algorithms for HCC using LRTs are based on staged sessions separated by weeks/months, it is of interest to correlate these variables in a time-dependent fashion. Does AFP response correlate with imaging response, or is it better able to predict survival than imaging response [10], [23]? Establishing a correlation between AFP and imaging response has the potential to help assess response in clinical scenarios where standard cross-sectional imaging findings are equivocal.
Recently, three novel statistical methods were used to demonstrate the importance of imaging response in HCC; the study concluded that tumor response was a potentially significant surrogate of survival [22]. Given the well-known difficulties in assessing treatment response in HCC (inter-observer subjectivity, scan thickness, variable enhancement, regenerative/dysplastic nodules, perfusional abnormalities), we hypothesized that AFP response (objective, no inter-observer variability) may provide a simple, reproducible and potentially less subjective method of response assessment [10], [23]. We performed a comprehensive study addressing whether: (a) AFP correlates with imaging response by WHO and EASL methodologies, and (b) if AFP response can predict improved survival.
Section snippets
Materials and methods
This study was compliant with the Health Insurance Portability and Accountability Act and approved by the Northwestern University Institutional Review Board. Between 2000 and 2010, 629 HCC patients were treated with LRTs (90Y: N = 406; TACE: N = 223); this constitutes the source population. Patients were eligible for LRTs if they exhibited unresectable HCC and bilirubin <3.0 mg/dl (discussed at weekly multidisciplinary HCC conference). To create the study population for this specific analysis, we
Baseline characteristics
Table 1 describes the baseline characteristics. 28 (55%) were ⩾65, 30 (59%) were male, and 48 (94%) were treatment naive. Eighteen patients were diagnosed by biopsy. Tumor grade information was only available for 9 patients (well-differentiated: N = 3, moderately differentiated: N = 2, poorly-differentiated: N = 4). Baseline imaging, laboratory characteristics and cancer stages are also summarized.
AFP-imaging response correlation
Table 2 summarizes the correlation between AFP and imaging response by WHO and EASL guidelines at 3 and 6
Discussion
HCC patients usually present beyond potentially curative options [42]. In this scenario, systemic agents and LRTs have an established palliative role [3], [4], [7], [8], [12], [26]. Consequently, response assessment following LRTs has also been extensively studied in order to develop appropriate guidelines for accurate response monitoring [10], [26], [33]. AFP may play a potential role in this scenario, where, combined with imaging, it may improve the ability to assess treatment response and
Conclusions
This study investigates AFP response in a time-dependent fashion. AFP response assessment is simple, reproducible, operator-independent and is highly sensitive for detecting radiologic response. Response by AFP and EASL predicts improved survival. Consideration should be made to develop HCC treatments that not only prolong TTP, but also elicit AFP and tumor response [22]. Future research should focus on incorporating AFP in response assessment methodologies.
Financial support
There was no funding provided for this study. R.S. and R.A.O. are supported in part by NIH Grant CA126809.
Conflict of interest
The underlying research reported in this study was funded by the NIH Institutes of Health.
References (47)
- et al.
Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial
Lancet Oncol
(2009) - et al.
Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes
Gastroenterology
(2010) - et al.
A comparative analysis of transarterial downstaging for hepatocellular carcinoma: chemoembolization versus radioembolization
Am J Transplant
(2009) - et al.
Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial
Lancet
(2002) - et al.
Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival
J Vasc Interv Radiol
(2005) - et al.
Role of the EASL, RECIST, and WHO response guidelines alone or in combination for hepatocellular carcinoma: radiologic–pathologic correlation
J Hepatol
(2011) - et al.
Radioembolization with 90Yttrium microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies: Part 1. Technical and methodologic considerations
J Vasc Interv Radiol
(2006) - et al.
Research reporting standards for radioembolization of hepatic malignancies
J Vasc Interv Radiol
(2011) - et al.
Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver
J Hepatol
(2001) The resurrection of alphafetoprotein
J Hepatol
(2010)
Hepatocellular carcinoma and hepatitis C in the United States
Hepatology
Hepatocellular carcinoma incidence, mortality, and survival benefits in the United States from 1975 to 2005
J Clin Oncol
Sorafenib in advanced hepatocellular carcinoma
N Engl J Med
Drop-out rates of patients with hepatocellular cancer listed for liver transplantation: outcome with chemoembolization
Liver Transpl
Safety and efficacy of (90)Y radiotherapy for hepatocellular carcinoma with and without portal vein thrombosis
Hepatology
Chemoembolization for hepatocellular carcinoma: comprehensive imaging and survival analysis in a 172-patient cohort
Radiology
Imaging response in the primary index lesion and clinical outcomes following transarterial locoregional therapy for hepatocellular carcinoma
JAMA
Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma
Gastroenterology
Survival after Yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation
Hepatology
Randomized control trials on chemoembolization for hepatocellular carcinoma: is there room for new studies?
J Clin Gastroenterol
Clinical features and prognosis of hepatocellular carcinoma with reference to serum alpha-fetoprotein levels. Analysis of 606 patients
Cancer
Alpha-fetoprotein monitoring in Chinese patients with chronic hepatitis B virus infection: role in the early detection of hepatocellular carcinoma
Hepatology
Alpha-fetoprotein response after locoregional therapy for hepatocellular carcinoma: oncologic marker of radiologic response, progression, and survival
J Clin Oncol
Cited by (81)
Conversion to resection post radioembolization in patients with HCC: recommendations from a multidisciplinary working group
2022, HPBCitation Excerpt :Radiation lobectomy is also importantly a direct stress test for the liver, confirming the capacity of the liver to regenerate. Patients who meet the conditions listed in (a) are expected to tolerate TARE well and should respond with regeneration of liver volumes.15,17–22 The administration and response to TARE reliably validate this presumption.
Surveillance and Monitoring of Hepatocellular Carcinoma During the COVID-19 Pandemic
2021, Clinical Gastroenterology and HepatologyCitation Excerpt :Therefore, especially during the COVID-19 pandemic, imaging after Y-90 or SBRT can likely be delayed and performed ∼3–4 months after therapy (Table 3). AFP can also potentially be used as a marker for response to LRT, with imaging being delayed in patients with a significant drop in AFP from baseline (eg, >50%).53 Patients without viable disease after any form of LRT are recommended to undergo follow-up imaging every 3–4 months,50 although this also may be delayed in light of COVID-19 exposure risk, particularly for those with durable responses.
Alpha-Fetoprotein, Des-Gamma-Carboxy Prothrombin, and Modified RECIST Response as Predictors of Survival after Transarterial Radioembolization for Hepatocellular Carcinoma
2019, Journal of Vascular and Interventional RadiologyPrognostic model for unresectable hepatocellular carcinoma treated with dual PD-1 and angiogenesis blockade therapy
2024, Journal for ImmunoTherapy of Cancer