title: Phase I trial of selective internal radiation therapy for chemorefractory colorectal cancer liver metastases progressing after hepatic arterial pump and systemic chemotherapy.
abstract: BACKGROUND
  This prospective study assessed the safety and outcomes of selective internal radiation therapy (SIRT) using yttrium-90 ((90)Y) resin microspheres as a salvage therapy for liver-predominant metastases of colorectal cancer in patients with documented progression after hepatic arterial chemotherapy (HAC) and systemic chemotherapy.
  
  
  METHODS
  We recruited 19 patients who had received a mean of 2.9 prior lines of chemotherapy and ≥ 1 line of HAC. Dose-limiting toxicities (grade 3 or higher) were catalogued using Common Terminology Criteria for Adverse Events version 3.0. At 4 to 8 weeks and 3 to 4 months post SIRT, responses were assessed by carcinoembryonic antigen (CEA), and quantitative imaging using Response Evaluation Criteria in Solid Tumors (RECIST) and PET Response Criteria in Solid Tumors (PERCIST). Liver progression-free survival (LPFS), progression-free survival (PFS), and overall survival (OS) were calculated using Kaplan-Meier methodology.
  
  
  RESULTS
  Median follow-up was 31.2 months after SIRT. Within 6 weeks of SIRT, 3 patients (15.8%) experienced grade 3 toxicity. There was no incidence of radiation-induced liver disease. Responses by RECIST, PERCIST, and CEA were, respectively, 0%, 20%, and 32% at 4 to 8 weeks and 5%, 33%, and 21% at 3 to 4 months post SIRT; 53% of patients had stable disease (by RECIST) at 3 to 4 months. Of 19 patients, 4 (21.1%) had liver ablation, 9 (47%) received additional HAC, and 17 (89%) received systemic chemotherapy after SIRT. Median LPFS, PFS, and OS after SIRT were 5.2 months, 2.0 months, and 14.9 months, respectively.
  
  
  CONCLUSIONS
  SIRT was well tolerated and did not prohibit subsequent treatment, resulting in a median OS of 14.9 months in this heavily pretreated population.
authors.affiliation: Interventional Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY. Electronic address: sofoclec@mskcc.org.
authors.forename: Constantinos T
authors.initials: CT
authors.lastname: Sofocleous
authors.affiliation: Interventional Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Alessandra R
authors.initials: AR
authors.lastname: Garcia
authors.affiliation: Molecular Imaging and Therapy Service, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Neeta
authors.initials: N
authors.lastname: Pandit-Taskar
authors.affiliation: Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Kinh G
authors.initials: KG
authors.lastname: Do
authors.affiliation: Interventional Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Lynn A
authors.initials: LA
authors.lastname: Brody
authors.affiliation: Interventional Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Elena N
authors.initials: EN
authors.lastname: Petre
authors.affiliation: Department of Epidemiology & Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Marinela
authors.initials: M
authors.lastname: Capanu
authors.affiliation: Interventional Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Anne P
authors.initials: AP
authors.lastname: Longing
authors.affiliation: Department of Epidemiology & Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Joanne F
authors.initials: JF
authors.lastname: Chou
authors.affiliation: Molecular Imaging and Therapy Service, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Carrasquillo
authors.affiliation: Department of Medicine-Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Kemeny
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D001918:Brachytherapy / Q000379:methods*; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000532:radiotherapy; D016879:Salvage Therapy / Q000379:methods; D015021:Yttrium Radioisotopes / Q000008:administration & dosage*
chemical_list: D015021:Yttrium Radioisotopes
keywords: Arterially directed therapies; Hepatic arterial chemotherapy; Hepatic malignancy; Radioembolization; SIRT; Yttrium 90