title: A multicentric phase II clinical trial on intra-arterial hepatic radiotherapy with 90yttrium SIR-spheres in unresectable, colorectal liver metastases refractory to i.v. chemotherapy: preliminary results on toxicity and response rates.
abstract: BACKGROUND
  In patients locally progressing after two lines of chemotherapy, some locoregional approaches showed encouraging results in terms of local control of disease. The aim of our study was to evaluate toxicity, clinical response and quality of life in 48 patients with unresectable colorectal liver metastases submitted to selective internal radiotherapy (SIRT).
  
  
  METHODS
  Up to now 35 patients with unresectable colorectal liver metastases, refractory to two lines of chemotherapy, underwent intra-arterial infusion of resin microspheres with yttrium-90 (SIR-spheres). Pre-treatment evaluation included a CT scan, blood tests, a PET scan and arteriography of celiac trunk, hepatic and superior mesenteric artery; extrahepatic uptakes and pulmonary shunts more than 10% were excluded by a Scinti-scan. The gastroduodenal artery was embolized before the SIR-spheres injection. Other exclusion criteria were liver dysfunction and anatomical vascular anomalies. The clinical response was evaluated by CT-scan following the RECIST criteria. Median follow-up was 4 months.
  
  
  RESULTS
  Median number of metastases was 4 (range, 1-15), 38% of cases presenting hepatic involvement < 25%. The median SIRT dose delivered was 1.7 GBq. Median pulmonary shunt was 6%. No operative mortality occurred; early toxicity (within 48 hours) was 20.6%, shown as fever, acute pain and leucocytosis. The late toxicity was 24.1% with chronic pain, jaundice and nausea being the most frequent. All the toxic events were graded 2 or 3 according to the WHO scale. Preliminary results were available in terms of clinical response after 6 weeks: 12.5% had a partial response, 75% a stable disease, while progression of disease, was observed in 12.5% of the patients.
  
  
  CONCLUSIONS
  SIRT is a safe treatment in terms of acute and late toxicity. Intra-arterial microspheres could represent a good therapeutic option for patients with progressing liver metastases only, after two lines of systemic chemotherapy.
authors.affiliation: Regina Elena Cancer Institute, Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Mancini
authors.forename: L
authors.initials: L
authors.lastname: Carpanese
authors.forename: R
authors.initials: R
authors.lastname: Sciuto
authors.forename: G
authors.initials: G
authors.lastname: Pizzi
authors.forename: R
authors.initials: R
authors.lastname: Golfieri
authors.forename: L
authors.initials: L
authors.lastname: Giampalma
authors.forename: A
authors.initials: A
authors.lastname: Cappelli
authors.forename: M C
authors.initials: MC
authors.lastname: Galaverni
authors.forename: A
authors.initials: A
authors.lastname: Blotta
authors.forename: F
authors.initials: F
authors.lastname: Fiore
authors.forename: F
authors.initials: F
authors.lastname: Izzo
authors.forename: S
authors.initials: S
authors.lastname: Lastoria
authors.forename: A
authors.initials: A
authors.lastname: Mastro
authors.forename: M
authors.initials: M
authors.lastname: Di Marzo
authors.forename: P P
authors.initials: PP
authors.lastname: Cagol
authors.forename: D
authors.initials: D
authors.lastname: Gasparini
authors.forename: O
authors.initials: O
authors.lastname: Geatti
authors.forename: S
authors.initials: S
authors.lastname: Bacchetti
authors.forename: E
authors.initials: E
authors.lastname: Pasqual
authors.forename: M
authors.initials: M
authors.lastname: Zeuli
authors.forename: G
authors.initials: G
authors.lastname: Paoletti
authors.forename: C
authors.initials: C
authors.lastname: Garufi
authors.forename: M
authors.initials: M
authors.lastname: Cosimelli
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D018450:Disease Progression; D006801:Humans; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000532:radiotherapy* / Q000556:secondary*; D008863:Microspheres; D011446:Prospective Studies; D011788:Quality of Life; D011879:Radiotherapy Dosage; D013997:Time Factors; D016896:Treatment Outcome; D015021:Yttrium Radioisotopes / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000970:Antineoplastic Agents; D015021:Yttrium Radioisotopes