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Was Adjuvant Immunotherapy Really Effective to Reduce Hepatocellular Carcinoma Recurrence?
Gastroenterology 2015;-:1
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CORRESPONDENCE Readers may submit letters to the editor concerning articles that appeared in Gastroenterology within one month of publication. Detailed guidelines regarding the content are included in the Instructions to Authors.
Was Adjuvant Immunotherapy Really Effective to Reduce Hepatocellular Carcinoma Recurrence? Dear Editor: I read with interest the article by Lee et al regarding the use of autologous cytokine-induced killer cells to reduce post-treatment recurrence of hepatocellular carcinoma (HCC).1 It is encouraging for hepatologists to find out the benefits of adjuvant therapy with cytokine-induced killer cells in the increase of recurrence-free and overall survival in HCC patients. However, some points need clarification. The biggest tumor size in this study was only 3.1 cm, including patients treated with surgical resection. It is unknown whether patients with bigger HCC size were intentionally excluded or not encountered. As shown in the trial, the median tumor size was 2.3 cm in the control group, significantly higher than the median size of 1.8 cm in the immunotherapy group. Previous studies have shown that tumor size is the determinant factor in predicting of HCC recurrence after curative therapy.2–4 Thus, it is expected that more recurrence could be anticipated to occur in the control group as compared with the immunotherapy group, (49% vs 40%, respectively). Theoretically, patients with tumor recurrence should receive imaging studies more frequently. However, the mean number of overall imaging studies was 9.0±4.6 per participant in the immunotherapy group, significantly higher than the number of 7.1 ± 4.8 per patient in the control group. It appeared that the patients in the control group were not scheduled to receive follow-up imaging studies at similar interval. A total of 15 deaths were recorded, 3 patients in the immunotherapy group and 12
patients in the control group. Apart from 3 deaths of unknown causes in the control group, all died of HCC recurrence. Since more than 62% of these patients were associated with cirrhosis, it was very unlikely that none died of hepatic failure or complications of cirrhosis.5 Moreover, immunotherapy was not instituted after HCC recurrence. A study of slight difference in recurrence rates with similar treatment options, resulting in significant difference in overall survival should be interpreted with caution. Therefore, before we could draw a final conclusion, a well conducted study with similar baseline characteristics, similar follow-up imaging studies and treatment of recurrence for both groups is required. Q3 GIN-HO LO Department of Medical Research Digestive Center, E-DA Hospital, Kaohsiung School of Medicine for international students I- Shou University Kaohsiung, Taiwan
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References 1. 2. 3. 4. 5.
Lee JY, et al. Gastroenterology 2015;148:1383–1391. Liao WJ, et al. World J Gastroenterol 2010;28(16): 5135–5138. Lam VW, et al. J Am Coll Surg 2008;207:20–29. Wu JC, et al. J Hepatol 2009;51:890–897. Okuda K, et al. Cancer 1985;56:918–928.
Conflicts of interest The authors disclose no conflicts.
http://dx.doi.org/10.1053/j.gastro.2015.07.069
COR 5.4.0 DTD YGAST60015_proof 30 September 2015 2:06 pm ce
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CORRESPONDENCE Readers may submit letters to the editor concerning articles that appeared in Gastroenterology within one month of publication. Detailed guidelines regarding the content are included in the Instructions to Authors.
Was Adjuvant Immunotherapy Really Effective to Reduce Hepatocellular Carcinoma Recurrence? Dear Editor: I read with interest the article by Lee et al regarding the use of autologous cytokine-induced killer cells to reduce post-treatment recurrence of hepatocellular carcinoma (HCC).1 It is encouraging for hepatologists to find out the benefits of adjuvant therapy with cytokine-induced killer cells in the increase of recurrence-free and overall survival in HCC patients. However, some points need clarification. The biggest tumor size in this study was only 3.1 cm, including patients treated with surgical resection. It is unknown whether patients with bigger HCC size were intentionally excluded or not encountered. As shown in the trial, the median tumor size was 2.3 cm in the control group, significantly higher than the median size of 1.8 cm in the immunotherapy group. Previous studies have shown that tumor size is the determinant factor in predicting of HCC recurrence after curative therapy.2–4 Thus, it is expected that more recurrence could be anticipated to occur in the control group as compared with the immunotherapy group, (49% vs 40%, respectively). Theoretically, patients with tumor recurrence should receive imaging studies more frequently. However, the mean number of overall imaging studies was 9.0±4.6 per participant in the immunotherapy group, significantly higher than the number of 7.1 ± 4.8 per patient in the control group. It appeared that the patients in the control group were not scheduled to receive follow-up imaging studies at similar interval. A total of 15 deaths were recorded, 3 patients in the immunotherapy group and 12
patients in the control group. Apart from 3 deaths of unknown causes in the control group, all died of HCC recurrence. Since more than 62% of these patients were associated with cirrhosis, it was very unlikely that none died of hepatic failure or complications of cirrhosis.5 Moreover, immunotherapy was not instituted after HCC recurrence. A study of slight difference in recurrence rates with similar treatment options, resulting in significant difference in overall survival should be interpreted with caution. Therefore, before we could draw a final conclusion, a well conducted study with similar baseline characteristics, similar follow-up imaging studies and treatment of recurrence for both groups is required. Q3 GIN-HO LO Department of Medical Research Digestive Center, E-DA Hospital, Kaohsiung School of Medicine for international students I- Shou University Kaohsiung, Taiwan
Q1
References 1. 2. 3. 4. 5.
Lee JY, et al. Gastroenterology 2015;148:1383–1391. Liao WJ, et al. World J Gastroenterol 2010;28(16): 5135–5138. Lam VW, et al. J Am Coll Surg 2008;207:20–29. Wu JC, et al. J Hepatol 2009;51:890–897. Okuda K, et al. Cancer 1985;56:918–928.
Conflicts of interest The authors disclose no conflicts.
http://dx.doi.org/10.1053/j.gastro.2015.07.069
COR 5.4.0 DTD YGAST60015_proof 30 September 2015 2:06 pm ce
Q2
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