title: Feasibility and utility of re-treatment with (177)Lu-DOTATATE in GEP-NENs relapsed after treatment with (90)Y-DOTATOC.
abstract: OBJECTIVE
  Peptide receptor radionuclide therapy (PRRT) is a valid therapy for grade 1/2 gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). Although a median progression-free survival (PFS) of more than 20 months is frequently observed, the majority of patients relapse after 2 - 3 years. In the present study, we investigated the use of low dosage re-treatment with (177)Lu-DOTATATE (Lu-PRRT) in patients with GEP-NENs who relapsed after treatment with (90)Y-DOTATOC (Y-PRRT).
  
  
  METHODS
  Upon tumour progression, 26 patients with a PFS of at least 12 months after Y-PRRT were consecutively enrolled in a phase II study of re-treatment with Lu-PRRT. All patients had preserved kidney and haematological parameters and received 14.8 - 18.5 GBq of Lu-PRRT in four or five cycles. The disease control rate (DCR), toxicity, PFS and prognostic factors were evaluated.
  
  
  RESULTS
  Median total activity of Lu-PRRT was 16.5 GBq in five cycles. The DCR was 84.6%, median PFS was 22 months (95% CI 16 months - not reached) compared to 28 months (95% CI 20 - 36 months) after Y-PRRT. Tumour burden and number of liver metastases were important prognostic factors. Toxicity was mild after Lu-PRRT re-treatment in the majority of patients, with only two patients with grade 2 and one with grade 3 bone marrow toxicity; one patient had grade 2 and one grade 3 renal toxicity.
  
  
  CONCLUSIONS
  Patients with GEP-NEN who have previously responded to Y-PRRT are suitable candidates for Lu-PRRT re-treatment on progression. Although our sample size was limited, low-dosage Lu-PRRT was safe, and led to DCR and PFS rates comparable with those observed when Y-PRRT was used as primary treatment.
authors.affiliation: Nuclear Medicine Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Maroncelli 40, 47014, Meldola, FC, Italy. stefano.severi@irst.emr.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Severi
authors.affiliation: Nuclear Medicine Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Maroncelli 40, 47014, Meldola, FC, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Sansovini
authors.affiliation: Nuclear Medicine Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Maroncelli 40, 47014, Meldola, FC, Italy.
authors.forename: Annarita
authors.initials: A
authors.lastname: Ianniello
authors.affiliation: Division of Nuclear Medicine, European Institute of Oncology, Milan, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Bodei
authors.affiliation: Nuclear Medicine Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Maroncelli 40, 47014, Meldola, FC, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Nicolini
authors.affiliation: Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Toni
authors.initials: T
authors.lastname: Ibrahim
authors.affiliation: Oncology Pharmacy Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Di Iorio
authors.affiliation: Medical Physics Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: D'Errico
authors.affiliation: Nuclear Medicine Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Maroncelli 40, 47014, Meldola, FC, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Caroli
authors.affiliation: Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Monti
authors.affiliation: Nuclear Medicine Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Maroncelli 40, 47014, Meldola, FC, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Paganelli
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000532:radiotherapy*; D015282:Octreotide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D019233:Retreatment
chemical_list: D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C496730:90Y-octreotide, DOTA-Tyr(3)-; C447941:lutetium Lu 177 dotatate; D015282:Octreotide
keywords: 177Lu-DOTATATE; 90Y-DOTATOC; Gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs); Peptide receptor radionuclide therapy (PRRT)