D on histology, or by meeting radiological criteria for HCC by dynamic contrast-enhanced computed tomography or magnetic resonance imaging ), with supporting evidence according to good serology for hepatitis B or C virus, or serum alpha-fetoprotein above typical range . All sufferers had been $18 years of age, had measurable illness, sufficient renal function, hemopoietic function Post-RE and Pre-sorafenib Post-sorafenib Month 1 12 12 $3 7 Month two 12 6 $3 three Month three 12 5 $3 three Month 4+ 12 ten $3 four Grade, N of individuals Any Blood and lymph Anemia Leukopenia Thrombocytopenia Gastrointestinal Abdominal distension Ascites Diarrhea Autophagy Nausea Upper GI hemorrhage Vomiting 12 13 $3 15 12 4 $3 1 1 1 1 1 1 1 1 1 9 2 1 three 1 three 1 6 1 1 1 two 1 1 1 General/administration site Lethargy Mucosal inflammation Pyrexia Hepatobiliary Elevated ALP Elevated ALT Elevated AST Hepatitis Hyperbilirubinemia Hypoalbuminemia Infections and infestations Sepsis Viral infection Injury, poisoning and procedural complications Fall Radiation skin injury Skin toxicity Metabolism and nutrition Decreased appetite Renal and urinary Urinary tract infection Reproductive method Scrotal pain 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 3 1 1 1 1 1 1 two 1 1 1 1 1 1 1 two 1 1 1 1 1 1 1 1 1 1 Respiratory, thoracic and mediastinal Chest discomfort Hemoptysis Pneumonia Pneumonitis 1 1 1 1 { 1 1 1 1 1 { Skin and subcutaneous 4 Sorafenib-Radioembolization Therapy for HCC Overall incidence Post-RE and Pre-sorafenib Post-sorafenib Month 1 12 $3 Month 2 12 $3 Month 3 12 1 2 1 2 1 2 1 1 3 3 2 $3 Month 4+ 12 $3 Grade, N of patients Acne Alopecia Hand-foot syndrome Rash Vascular Gingival bleeding Hypertension 12 1 6 7 5 $3 12 $3 5 1 5 3 1 2 1 1 2 Treatment-related toxicities included all those assessed as either definitely, probably, possibly related to treatment and unlikely to be related to treatment; If a toxicity occurred multiple times to the same patient, it was counted once for that patient at the highest grade that was assessed.Post-RE: Post-radioembolization/Pre-sorafenib period of 14 days; N = number of patients alive at each time interval; National Cancer Institute Common Terminology Criteria for Adverse Events version 3. Abbreviations: ALP: alkaline phosphatase; ALT: alanine transaminase; AST: aspartate aminotransferase GI: gastrintestinal. { This was a grade 5 event. doi:10.1371/journal.pone.0090909.t002 hemoglobin.9.5 g/dL), and Eastern Cooperative Oncology Group performance status 0 or 1. In addition, eligible patients were required to have: 1) sufficient liver function for safe delivery of radioembolization, defined as: an absence of ascites or synthetic liver dysfunction, International Normalized Ratio #2.0; albumin $2.5 g/dL and aspartate 11967625 transaminase, alanine transaminase and alkaline phosphatase each #56 upper limit of normal; 2) hepatic arterial anatomy that would enable safe delivery of microspheres to the liver only; 3) without excess hepato-pulmonary shunting; or 4) without main trunk portal vein thrombosis. Premenopausal, sexuallyactive individuals were required to use two forms of contraception during the study. Patients were excluded if they were pregnant or breast feeding or had been previously treated with external beam radiotherapy to the liver or were currently receiving any other investigational agent. Radioembolization Radioembolization is a form of brachytherapy during which 90Y microspheres are delivered via a temporary transfemoral catheter advanced under fluoroscopic guidance into.D on histology, or by meeting radiological criteria for HCC by dynamic contrast-enhanced computed tomography or magnetic resonance imaging ), with supporting evidence according to optimistic serology for hepatitis B or C virus, or serum alpha-fetoprotein above Epigenetics normal range . All patients had been $18 years of age, had measurable disease, sufficient renal function, hemopoietic function Post-RE and Pre-sorafenib Post-sorafenib Month 1 12 12 $3 7 Month 2 12 six $3 three Month 3 12 5 $3 3 Month 4+ 12 ten $3 four Grade, N of sufferers Any Blood and lymph Anemia Leukopenia Thrombocytopenia Gastrointestinal Abdominal distension Ascites Diarrhea Nausea Upper GI hemorrhage Vomiting 12 13 $3 15 12 four $3 1 1 1 1 1 1 1 1 1 9 two 1 three 1 3 1 six 1 1 1 2 1 1 1 General/administration web site Lethargy Mucosal inflammation Pyrexia Hepatobiliary Elevated ALP Elevated ALT Elevated AST Hepatitis Hyperbilirubinemia Hypoalbuminemia Infections and infestations Sepsis Viral infection Injury, poisoning and procedural complications Fall Radiation skin injury Skin toxicity Metabolism and nutrition Decreased appetite Renal and urinary Urinary tract infection Reproductive method Scrotal discomfort 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 three 1 1 1 1 1 1 two 1 1 1 1 1 1 1 two 1 1 1 1 1 1 1 1 1 1 Respiratory, thoracic and mediastinal Chest discomfort Hemoptysis Pneumonia Pneumonitis 1 1 1 1 { 1 1 1 1 1 { Skin and subcutaneous 4 Sorafenib-Radioembolization Therapy for HCC Overall incidence Post-RE and Pre-sorafenib Post-sorafenib Month 1 12 $3 Month 2 12 $3 Month 3 12 1 2 1 2 1 2 1 1 3 3 2 $3 Month 4+ 12 $3 Grade, N of patients Acne Alopecia Hand-foot syndrome Rash Vascular Gingival bleeding Hypertension 12 1 6 7 5 $3 12 $3 5 1 5 3 1 2 1 1 2 Treatment-related toxicities included all those assessed as either definitely, probably, possibly related to treatment and unlikely to be related to treatment; If a toxicity occurred multiple times to the same patient, it was counted once for that patient at the highest grade that was assessed.Post-RE: Post-radioembolization/Pre-sorafenib period of 14 days; N = number of patients alive at each time interval; National Cancer Institute Common Terminology Criteria for Adverse Events version 3. Abbreviations: ALP: alkaline phosphatase; ALT: alanine transaminase; AST: aspartate aminotransferase GI: gastrintestinal. { This was a grade 5 event. doi:10.1371/journal.pone.0090909.t002 hemoglobin.9.5 g/dL), and Eastern Cooperative Oncology Group performance status 0 or 1. In addition, eligible patients were required to have: 1) sufficient liver function for safe delivery of radioembolization, defined as: an absence of ascites or synthetic liver dysfunction, International Normalized Ratio #2.0; albumin $2.5 g/dL and aspartate 11967625 transaminase, alanine transaminase and alkaline phosphatase each #56 upper limit of normal; 2) hepatic arterial anatomy that would enable safe delivery of microspheres to the liver only; 3) without excess hepato-pulmonary shunting; or 4) without main trunk portal vein thrombosis. Premenopausal, sexuallyactive individuals were required to use two forms of contraception during the study. Patients were excluded if they were pregnant or breast feeding or had been previously treated with external beam radiotherapy to the liver or were currently receiving any other investigational agent. Radioembolization Radioembolization is a form of brachytherapy during which 90Y microspheres are delivered via a temporary transfemoral catheter advanced under fluoroscopic guidance into.