Response to the Comment on “Prediction of Hepatocellular Carcinoma Recurrence Beyond Milan Criteria After Resection: Validation of a Clinical Risk Score in Aninternational Cohort”

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Dear Dr Yu et al,Our study validated a clinical risk score to predict recurrence following resection of hepatocellular carcinoma (HCC).1 Thank you for asking these very important and insightful questions about the impact of surveillance practice on the recurrence pattern following these curative intent resections. The National Comprehensive Cancer Network (NCCN) guideline recommends cross-sectional imaging at 3 to 6-month intervals for the first 2 years and then every 6 to 12 months thereafter.2 In addition, if patients had elevated preoperative alpha-fetoprotein (AFP), they should be measured every 3 months for 2 years postoperatively, and then every 6 months thereafter. As our study included 5 different institutions spanning North America, Europe, and Asia, the practice may vary slightly depending on insurance coverage under different health care systems, institutional resources, and patients’ social factors.At Memorial Sloan Kettering Cancer Center, we evaluate patients within 2 weeks postoperatively, then follow them every 3 to 4 months in the first 2 years, and then every 6 months thereafter. For surveillance studies, we utilized AFP and liver function tests, and serial computed tomography (CT) scan and/or magnetic resonance imaging (MRI) as per NCCN guideline.3 In addition, we have a Cancer Registry that contacts patients and their providers annually to obtain updated disease status for our prospectively maintained database. During surveillance, when there is a question of recurrence, we review patients’ clinical and radiologic information at our weekly Disease Management Team meeting, which are well attended by surgical oncologists, radiologists, medical and radiation oncologists, gastroenterologists, interventional radiologists, and pathologists.At Washington University at St. Louis and at University of Montreal in Canada, the surveillance practices are as recommended by NCCN. Similarly, at Erasmus Medical Center in the Netherlands, patients were followed postoperatively with CT or MRI combined with serum AFP at 3 to 6 month intervals for up to 2 years, and then followed by annually for up to 5 years.4At Singapore General Hospital and National Cancer Center in Singapore, the first follow-up posthepatectomy is usually in about 2 weeks to review postoperative recovery, and thereafter for HCC surveillance. Patients were followed at intervals of 3 to 6 months for the first 2 years and then at 6 to 12 monthly intervals as per NCCN guideline. Clinical surveillance consisted of clinical evaluations, serial AFP, and hepatic imaging using ultrasound, CT scan, or MRI as deemed appropriate by the surgeon. Of note, as these centers are tertiary referral centers, there are a substantial number of patients who travel from afar for resection and then receive follow-up with their local hepatologists. For example, medical tourism is a major component in Singapore as medical care is better than some of the neighboring Southeast Asian countries. This may affect median length of follow-up or frequency of follow-up, but the median follow-up was 4.5 years among Singaporean cohort.The impact of surveillance practice on recurrence pattern following resection of HCC is indeed a crucial question to address and should be further studied. In this study, we did not evaluate this question but it will be an important pursuit to evaluate the impact of the frequency and total length of serial imaging on earlier detection of HCC. However, given what we know about HCC growth kinetics, it would seem unlikely that differences in the timing of imaging studies of a few weeks or even a few months would ultimately change the findings, treatment, or prognosis for most patients. The actual impact will be further investigated. Thank you for your thoughtful comments on this letter to the editor.

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