title: Cohort study of somatostatin-based radiopeptide therapy with [(90)Y-DOTA]-TOC versus [(90)Y-DOTA]-TOC plus [(177)Lu-DOTA]-TOC in neuroendocrine cancers.
abstract: OBJECTIVE
  Radiopeptide therapy is commonly performed with a single radioisotope. We aimed to compare the effectiveness of somatostatin-based radiopeptide therapy with a single versus a combination of radioisotopes.
  
  
  METHODS
  In a cohort study, patients with metastasized neuroendocrine cancer were treated with repeated cycles of (90)yttrium-labeled tetraazacyclododecane-tetraacetic acid modified Tyr-octreotide ([(90)Y-DOTA]-TOC) or with cycles alternating between [(90)Y-DOTA]-TOC and (177)lutetium-labeled DOTA-TOC ([(177)Lu-DOTA]-TOC) until tumor progression or permanent toxicity. Multivariable Cox regression and competing risk regression were used to study predictors of survival and renal toxicity in patients completing three or more treatment cycles.
  
  
  RESULTS
  A total of 486 patients completed three or more treatment cycles; 237 patients received [(90)Y-DOTA]-TOC and 249 patients received [(90)Y-DOTA]-TOC + [(177)Lu-DOTA]-TOC. Patients receiving [(90)Y-DOTA]-TOC + [(177)Lu-DOTA]-TOC had a significantly longer survival than patients receiving [(90)Y-DOTA]-TOC alone (5.51 v 3.96 years; hazard ratio, 0.64; 95% CI, 0.47 to 0.88; P = .006). The rates of severe hematologic toxicities (6.3% v 4.4%; P = .25) and severe renal toxicity (8.9% v 11.2%; P = .47) were comparable in both groups.
  
  
  CONCLUSIONS
  [(90)Y-DOTA]-TOC + [(177)Lu-DOTA]-TOC was associated with improved overall survival compared with [(90)Y-DOTA]-TOC alone in patients completing three or more cycles of treatment. Contrary to the current practice in radiopeptide therapy, our results suggest an advantage of using a combination of radioisotopes.
authors.affiliation: University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland.
authors.forename: Linda
authors.initials: L
authors.lastname: Villard
authors.forename: Anna
authors.initials: A
authors.lastname: Romer
authors.forename: Nicolas
authors.initials: N
authors.lastname: Marincek
authors.forename: Philippe
authors.initials: P
authors.lastname: Brunner
authors.forename: Michael T
authors.initials: MT
authors.lastname: Koller
authors.forename: Christian
authors.initials: C
authors.lastname: Schindler
authors.forename: Quinn K T
authors.initials: QK
authors.lastname: Ng
authors.forename: Helmut R
authors.initials: HR
authors.lastname: Mäcke
authors.forename: Jan
authors.initials: J
authors.lastname: Müller-Brand
authors.forename: Christoph
authors.initials: C
authors.lastname: Rochlitz
authors.forename: Matthias
authors.initials: M
authors.lastname: Briel
authors.forename: Martin A
authors.initials: MA
authors.lastname: Walter
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000187:drug effects; D008187:Lutetium / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015282:Octreotide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016017:Odds Ratio; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000009:adverse effects*; D011868:Radioisotopes / Q000008:administration & dosage / Q000009:adverse effects; D013004:Somatostatin / Q000008:administration & dosage / Q000009:adverse effects; D015021:Yttrium Radioisotopes / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D009942:Organometallic Compounds; D011868:Radioisotopes; D015021:Yttrium Radioisotopes; D013004:Somatostatin; D008187:Lutetium; C496730:90Y-octreotide, DOTA-Tyr(3)-; C447941:lutetium Lu 177 dotatate; D015282:Octreotide