Hepatocellular carcinoma with complete response to the immunotherapy: the oncologist's dilemma.

| https://dx.doi. org/10.21037/hbsn-21-499 Hepatocellular carcinoma (HCC) is the seventh most common cancer and the fourth leading cause of cancerrelated death worldwide (1). During the last decade, many efforts have been made to improve patient survival by conducting clinical trials investigating local and systemic treatment options for patients with unresectable tumors. However, despite significant research efforts, only few treatment approaches have been validated for HCC. Immunotherapy is a novel treatment approach representing an effective, promising and safe option against HCC. Recently, six systemic therapies have been approved based on phase III trials (atezolizumab plus bevacizumab, sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab) and three additional therapies have obtained accelerated Food and Drug Administration (FDA) approval owing to evidence of efficacy (2). The combination of atezolizumab and bevacizumab is the current standard of care for patients with locally advanced or metastatic HCC. The approval of the combination was based on IMbrave 150 study which showed clear superiority over Sorafenib in terms of OS [hazard ratio (HR) 0.66; 95% CI: 0.92–0.85; P=0.0006] and median PFS (HR 0.59; 95% CI: 0.47–0.76; P<0.0001). Moreover, there was tripling of response from 11% for Sorafenib to 30% for atezolizumab and bevacizumab with 7.7% achieving complete response (3). HCC is an aggressive disease with poor prognosis with median overall survival, 10.7–13.4 months (Sharp and IMbrave study) when treated with Sorafenib (3,4). However, the use of atezolizumab and bevacizumab has resulted in significant improvement in median OS to 19.2 months and duration of response of 18.1 and 16.3 months on mRECIST scale (3). However, the increased use of immunotherapy has demonstrated a wide variety of imaging features and patterns of disease that cannot be adequately captured by traditional response criteria, such as the World Health Organization (WHO) criteria and Response Evaluation Criteria in Solid Tumors (RECIST), which have been used primarily with cytotoxic chemotherapies. In response to these observations, several novel response criteria have been developed to evaluate patients who receive immunotherapy. Thus, new criteria, such as immune-related response criteria (irRC), immune-related RECIST (irRECIST), and immune-RECIST (iRECIST), have been developed to assist clinicians in distinguishing between patients who are and are not responding to a particular treatment (5) (Table 1). P o s i t r o n e m i s s i o n t o m o g r a p h y ( P E T ) u s i n g 18F-fluorodeoxyglucose (F-FDG) is widely used for assessing a variety of malignancies, has poor sensitivity in the evaluation of HCC. In this effort, novel PET radiotracers (11C-acetate and 11C-choline) are currently being assessed. In addition, investigational use of magnetic resonance (MR) radiomics for depicting apoptosis and cytolysis to monitor cancer response also has been reported (6). Other radiology investigations are in various stages of development. In this setting, molecular imaging with immuno-positron emission tomography (immuno-PET) provides a noninvasive functional biomarker of tumor response for patients on immunotherapy (5). Therefore, a clinical management issue arises regarding Editorial