348
Correspondence / Digestive and Liver Disease 47 (2015) 347–349
It is important to assess clinically relevant outcomes in order to improve care. The availability of such data provides an essential benchmark against which future service change can be assessed. It is critical that interventions are validated against patient outcomes, as cost-effective use of resources is ever more important in healthcare. Our findings also demonstrate that parents and patients with IBD are still relatively poor judges of their own disease activity. Although this is more accurate when they are in remission, the high false-positive rate during active disease indicates that additional clinical parameters must be used to guide treatment decisions. Although self-reporting constitutes an important part of evaluating disease status, we must better understand the factors that inform this personal assessment before abandoning other, more objective, measures of disease activity. Conflict of interest None declared. References [1] Turner D, Griffiths AM, Walters TD, et al. Mathematical weighting of the pediatric Crohn’s disease activity index (PCDAI) and comparison with its other short versions. Inflammatory Bowel Diseases 2012;18:55–62. [2] Turner D, Otley AR, Mack D, et al. Development, validation, and evaluation of a pediatric ulcerative colitis activity index: a prospective multicenter study. Gastroenterology 2007;133:423–32.
Simona Gatti a,b Department of Paediatric Gastroenterology, Hepatology and Nutrition, Addenbrookes Hospital, Cambridge, United Kingdom b Department of Paediatrics, Marche Polytechnic University, Ancona, Italy a
Mary Brennan Robert Heuschkel Department of Paediatric Gastroenterology, Hepatology and Nutrition, Addenbrookes Hospital, Cambridge, United Kingdom Matthias Zilbauer a,b,c,∗ Department of Paediatric Gastroenterology, Hepatology and Nutrition, Addenbrookes Hospital, Cambridge, United Kingdom b University Department of Paediatrics, University of Cambridge, Cambridge, United Kingdom c Witten Herdecke University, Witten, Germany a
∗ Corresponding
author at: University Department of Paediatrics, Level 8 Addenbrooke’s Hospital, Box 116, Hills Road, Cambridge CB2 0QQ, United Kingdom. Tel.: +44 01223 336889; fax: +44 01223 586794. E-mail addresses: [email protected] (S. Gatti), [email protected] (M. Brennan), [email protected] (R. Heuschkel), [email protected] (M. Zilbauer). http://dx.doi.org/10.1016/j.dld.2014.11.013
Hepatocellular carcinoma as a second primary cancer in patients with chronic hepatitis C virus infection夽 Dear Editor, Individuals with hepatitis C virus (HCV) infection have 15–20 times the risk of HCC as compared to those without the infection [1]. Screening for HCC with liver ultrasound every 6 months is advocated for patients with chronic HCV infection and cirrhosis or advanced liver fibrosis (stage F3), even after attainment of sustained virological response (SVR) [2,3]. Approximately 7% of HCV-infected patients with nonliver first primary cancers developed HCC as a second primary cancer (SPC) [4]. The goal of the present study was to identify predictors of HCC as a SPC in HCVinfected patients. In this retrospective study, we identified patients with nonliver first primary cancers and chronic HCV infection (positive anti-HCV and detectable HCV RNA in serum) who were seen at our institution from January 2008 through December 2011. This protocol was approved by our Institutional Review Board. HCC was diagnosed by evaluation of liver mass by liver ultrasound (or computerized tomography scan) and/or biopsy [2]. HCV-infected patients with a nonliver first primary cancer who developed HCC as a SPC (cases) were matched 1:1 to those who did not develop HCC (controls) based on cirrhosis status and age (±5 years) at diagnosis of the first primary cancer. SVR was defined as absence of HCV RNA in the serum 24 weeks after discontinuation of HCV therapy [5]. Matched analysis was conducted and p < 0.05 was considered statistically significant. Thirty-two out of 476 (7%) HCV-infected patients with nonliver first primary cancers developed HCC as a SPC during the study period. Most cases had a solid tumour as the first primary cancer (81%). All patients were cirrhotics. Genotype 1 was the predominant HCV genotype (77%). HCC as a SPC was diagnosed as an incidental finding in most of the cases (75%). The most common treatment modalities for the first primary cancers in the cases were surgery (69%) and chemotherapy (34%). The most common chemotherapeutic agents administered were monoclonal antibodies (rituximab, bevacizumab, and trastuzumab) (n = 6); antimetabolites (cytarabine, methotrexate, capecitabine, and 5-fluorouracil) (n = 5); and systemic corticosteroids (n = 5). Most cases received HCV treatment (75%); majority of them did not achieve SVR (88%). When cases and controls were compared, more cases had solid tumours as the first primary cancer (82% vs. 47%), and had a progressive first primary cancer (76% vs. 47%) (Supplementary Table S1). More cases received HCV treatment (71% vs. 41%), mostly with standard (nonpegylated) interferon alpha 2-containing regimens (75% vs. 43%). None of the cases achieved SVR (0% vs. 29%). There were no significant differences between cases and controls with respect to other risk factors for HCC (Supplementary Table S1). This is the first study to evaluate predictors of HCC as a SPC in HCV-infected patients with a nonliver first primary cancer. HCC developed as a SPC mostly in patients who had solid tumours as first primary cancers and in patients whose first primary cancer was progressive. Most of the patients who developed HCC as a SPC had not achieved SVR. A majority of the cases in our series failed to achieve SVR, likely because a high number of patients were treated with standard interferon-containing regimens. SVR rates have improved with the approval of new direct-acting antivirals [5]. Patients eligible for
夽 Presented in part at the 50th Annual Meeting of the American Society for Clinical Oncology, Chicago IL, May 30–June 3, 2014.
Correspondence / Digestive and Liver Disease 47 (2015) 347–349
these new treatments should be identified early and treated to prevent HCC. Our study highlights that screening recommendations for HCC [2] should be followed in HCV-infected patients with nonliver cancers to ensure early detection of HCC as a SPC. In most patients in our study, HCC was diagnosed incidentally; very few patients had HCC detected on routine screening. Increased awareness regarding the importance of screening for HCC is needed among oncologists. Conflict of interest Dr. Torres is a consultant for Gilead Sciences, Merck & Co., Inc., Vertex Pharmaceuticals, Novartis, Genentech, Astellas, Pfizer, and Theravance, Inc., and received research grants from Merck & Co., Inc., and Vertex Pharmaceuticals. Other authors have nothing to disclose. Acknowledgement We thank Stephanie Deming for editorial assistance. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.dld.2014.12.005. References [1] El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 2012;142, 1264–73.e1. [2] EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. Journal of Hepatology 2012;56:908–43.
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[3] Aleman S, Rahbin N, Weiland O, et al. A risk for hepatocellular carcinoma persists long-term after sustained virologic response in patients with hepatitis C-associated liver cirrhosis. Clinical Infectious Diseases 2013;57:230–6. [4] Torres HA, Mahale P, Raad II, et al. Hepatitis C virus infection in patients with cancer: a single-institution experience in 642 patients. AASLD abstract. Hepatology 2013;58:1290A. [5] EASL clinical practice guidelines: management of hepatitis C virus infection. Journal of Hepatology 2014;60:392–420.
Parag Mahale Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Ahmed O. Kaseb Manal M. Hassan Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Harrys A. Torres ∗ Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA ∗ Corresponding
author at: Department of Infectious Diseases, Infection Control, and Employee Health, Unit 1460, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. Tel.: +1 713 792 6830; fax: +1 713 745 6839. E-mail address: [email protected] (H.A. Torres) http://dx.doi.org/10.1016/j.dld.2014.12.005
Correspondence / Digestive and Liver Disease 47 (2015) 347–349
It is important to assess clinically relevant outcomes in order to improve care. The availability of such data provides an essential benchmark against which future service change can be assessed. It is critical that interventions are validated against patient outcomes, as cost-effective use of resources is ever more important in healthcare. Our findings also demonstrate that parents and patients with IBD are still relatively poor judges of their own disease activity. Although this is more accurate when they are in remission, the high false-positive rate during active disease indicates that additional clinical parameters must be used to guide treatment decisions. Although self-reporting constitutes an important part of evaluating disease status, we must better understand the factors that inform this personal assessment before abandoning other, more objective, measures of disease activity. Conflict of interest None declared. References [1] Turner D, Griffiths AM, Walters TD, et al. Mathematical weighting of the pediatric Crohn’s disease activity index (PCDAI) and comparison with its other short versions. Inflammatory Bowel Diseases 2012;18:55–62. [2] Turner D, Otley AR, Mack D, et al. Development, validation, and evaluation of a pediatric ulcerative colitis activity index: a prospective multicenter study. Gastroenterology 2007;133:423–32.
Simona Gatti a,b Department of Paediatric Gastroenterology, Hepatology and Nutrition, Addenbrookes Hospital, Cambridge, United Kingdom b Department of Paediatrics, Marche Polytechnic University, Ancona, Italy a
Mary Brennan Robert Heuschkel Department of Paediatric Gastroenterology, Hepatology and Nutrition, Addenbrookes Hospital, Cambridge, United Kingdom Matthias Zilbauer a,b,c,∗ Department of Paediatric Gastroenterology, Hepatology and Nutrition, Addenbrookes Hospital, Cambridge, United Kingdom b University Department of Paediatrics, University of Cambridge, Cambridge, United Kingdom c Witten Herdecke University, Witten, Germany a
∗ Corresponding
author at: University Department of Paediatrics, Level 8 Addenbrooke’s Hospital, Box 116, Hills Road, Cambridge CB2 0QQ, United Kingdom. Tel.: +44 01223 336889; fax: +44 01223 586794. E-mail addresses: [email protected] (S. Gatti), [email protected] (M. Brennan), [email protected] (R. Heuschkel), [email protected] (M. Zilbauer). http://dx.doi.org/10.1016/j.dld.2014.11.013
Hepatocellular carcinoma as a second primary cancer in patients with chronic hepatitis C virus infection夽 Dear Editor, Individuals with hepatitis C virus (HCV) infection have 15–20 times the risk of HCC as compared to those without the infection [1]. Screening for HCC with liver ultrasound every 6 months is advocated for patients with chronic HCV infection and cirrhosis or advanced liver fibrosis (stage F3), even after attainment of sustained virological response (SVR) [2,3]. Approximately 7% of HCV-infected patients with nonliver first primary cancers developed HCC as a second primary cancer (SPC) [4]. The goal of the present study was to identify predictors of HCC as a SPC in HCVinfected patients. In this retrospective study, we identified patients with nonliver first primary cancers and chronic HCV infection (positive anti-HCV and detectable HCV RNA in serum) who were seen at our institution from January 2008 through December 2011. This protocol was approved by our Institutional Review Board. HCC was diagnosed by evaluation of liver mass by liver ultrasound (or computerized tomography scan) and/or biopsy [2]. HCV-infected patients with a nonliver first primary cancer who developed HCC as a SPC (cases) were matched 1:1 to those who did not develop HCC (controls) based on cirrhosis status and age (±5 years) at diagnosis of the first primary cancer. SVR was defined as absence of HCV RNA in the serum 24 weeks after discontinuation of HCV therapy [5]. Matched analysis was conducted and p < 0.05 was considered statistically significant. Thirty-two out of 476 (7%) HCV-infected patients with nonliver first primary cancers developed HCC as a SPC during the study period. Most cases had a solid tumour as the first primary cancer (81%). All patients were cirrhotics. Genotype 1 was the predominant HCV genotype (77%). HCC as a SPC was diagnosed as an incidental finding in most of the cases (75%). The most common treatment modalities for the first primary cancers in the cases were surgery (69%) and chemotherapy (34%). The most common chemotherapeutic agents administered were monoclonal antibodies (rituximab, bevacizumab, and trastuzumab) (n = 6); antimetabolites (cytarabine, methotrexate, capecitabine, and 5-fluorouracil) (n = 5); and systemic corticosteroids (n = 5). Most cases received HCV treatment (75%); majority of them did not achieve SVR (88%). When cases and controls were compared, more cases had solid tumours as the first primary cancer (82% vs. 47%), and had a progressive first primary cancer (76% vs. 47%) (Supplementary Table S1). More cases received HCV treatment (71% vs. 41%), mostly with standard (nonpegylated) interferon alpha 2-containing regimens (75% vs. 43%). None of the cases achieved SVR (0% vs. 29%). There were no significant differences between cases and controls with respect to other risk factors for HCC (Supplementary Table S1). This is the first study to evaluate predictors of HCC as a SPC in HCV-infected patients with a nonliver first primary cancer. HCC developed as a SPC mostly in patients who had solid tumours as first primary cancers and in patients whose first primary cancer was progressive. Most of the patients who developed HCC as a SPC had not achieved SVR. A majority of the cases in our series failed to achieve SVR, likely because a high number of patients were treated with standard interferon-containing regimens. SVR rates have improved with the approval of new direct-acting antivirals [5]. Patients eligible for
夽 Presented in part at the 50th Annual Meeting of the American Society for Clinical Oncology, Chicago IL, May 30–June 3, 2014.
Correspondence / Digestive and Liver Disease 47 (2015) 347–349
these new treatments should be identified early and treated to prevent HCC. Our study highlights that screening recommendations for HCC [2] should be followed in HCV-infected patients with nonliver cancers to ensure early detection of HCC as a SPC. In most patients in our study, HCC was diagnosed incidentally; very few patients had HCC detected on routine screening. Increased awareness regarding the importance of screening for HCC is needed among oncologists. Conflict of interest Dr. Torres is a consultant for Gilead Sciences, Merck & Co., Inc., Vertex Pharmaceuticals, Novartis, Genentech, Astellas, Pfizer, and Theravance, Inc., and received research grants from Merck & Co., Inc., and Vertex Pharmaceuticals. Other authors have nothing to disclose. Acknowledgement We thank Stephanie Deming for editorial assistance. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.dld.2014.12.005. References [1] El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 2012;142, 1264–73.e1. [2] EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. Journal of Hepatology 2012;56:908–43.
349
[3] Aleman S, Rahbin N, Weiland O, et al. A risk for hepatocellular carcinoma persists long-term after sustained virologic response in patients with hepatitis C-associated liver cirrhosis. Clinical Infectious Diseases 2013;57:230–6. [4] Torres HA, Mahale P, Raad II, et al. Hepatitis C virus infection in patients with cancer: a single-institution experience in 642 patients. AASLD abstract. Hepatology 2013;58:1290A. [5] EASL clinical practice guidelines: management of hepatitis C virus infection. Journal of Hepatology 2014;60:392–420.
Parag Mahale Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Ahmed O. Kaseb Manal M. Hassan Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Harrys A. Torres ∗ Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA ∗ Corresponding
author at: Department of Infectious Diseases, Infection Control, and Employee Health, Unit 1460, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. Tel.: +1 713 792 6830; fax: +1 713 745 6839. E-mail address: [email protected] (H.A. Torres) http://dx.doi.org/10.1016/j.dld.2014.12.005
