Peptide receptor radionuclide therapy in the management of gastrointestinal neuroendocrine tumors: efficacy profile, safety, and quality of life

Figures & data

Table 1 Summary of most relevant papers on PRRT in terms of center experience and number of patients treated

Study	Ligand	Number of patients	Tumor origin	Response criteria	OR (%)	SD (%)	DCR	PFS/TTP	Outcome
Imhof et al,^Citation7 2011	90Y-Dotatoc	1,109	NETs	RECIST	34	5.2	39	13 m	OS 23 m
Bushnell et al,^Citation8 2010	90Y-Dotatoc	90	NETs	SWOG	4 (PR)	70	74	16 m	Median OS 26 m
Kwekkeboom et al,^Citation21 2008	177Lu-Dotatate	310	GEP-NETs	SWOG	30	51	19	33 m	Median OS 46 ma
Ezziddin et al,^Citation22 2014	177Lu-Dotatate	68	PNETs	RECIST	60	25	15	34 m	Median OS 53 m
Garkavij et al,^Citation35 2010	177Lu-Dotatate	12	NETs	RECIST	17 (PR)	57	74	–	–
Swärd et al,^Citation36 2010	177Lu-Dotatate	26	NETs	RECIST	38	50	88	–	–
Bodei et al,^Citation37 2011	177Lu-Dotatate	42	NETs	RECIST	31	47	78	36 m	OS 36 m

Note:

a Median OS from start of treatment.

Abbreviations: OR, overall response; SD, stable disease; DCR, disease control rate; PFS, progression-free survival; TTP, time-to-progression; PR, partial response; OS, overall survival; m, months; GEP, gastroenteropancreatic; NETs, neuroendocrine tumors; PNETs, pancreatic NETs; RECIST, Response Evaluation Criteria in Solid Tumors; SWOG, Southwest Oncology Group; PRRT, peptide receptor radionuclide therapy; 90Y-Dotatoc, 90Y-DOTA-Tyr3-octreotide; 177Lu-Dotatate, 177Lu-DOTA-Tyr3-octreotate.

Figure 1 Patient with progressive GEP-NET treated at our institute.

Notes: Total body images acquired after the first (A) and fifth (B) cycle of 90Y-Dotatoc. Cumulative activity delivered was 8.14 GBq.
Abbreviations: GEP, gastroenteropancreatic; NET, neuroendocrine tumor; 90Y-Dotatoc, 90Y-DOTA-Tyr3-octreotide.

Table 2 Results of our experience of PRRT retreatment

Evaluation criteria	90Y-PRRT treatment	177Lu-PRRT retreatment	P-value
Number of patients	26	26
Median activity (range)	10.8 GBq (5–14.9)	16.5 GBq (5.5–22.2)
Median number of cycles	5 (2–7)	5 (2–5)
CR	1	1
PR	3	1
SD	22	20
PD	NA	4
Median PFS, months (95% CI)	28 (20–36)	22 (16–nr)	0.529
Median OS, months (95% CI)		36 (4–70)

Note: © Springer-Verlag Berlin Heidelberg 2015. Severi S, Sansovini M, Ianniello A, et al. Feasibility and utility of re-treatment with (177)Lu-DOTATATE in GEP-NENs relapsed after treatment with (90)Y-DOTATOC. Eur J Nucl Med Mol Imaging. 2015;42(13):1955–1963.³¹ With permission of Springer.

Abbreviations: CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; PFS, progression-free survival; OS, overall survival; nr, not reached; CI, confidence interval; PRRT, peptide receptor radionuclide therapy; NA, not applicable.

Figure 2 (A) PFS curves of the same group of patients after treatment with 90Y-Dotatoc and after retreatment with low-dose 177Lu-Dotatate. (B) OS curve for retreatment group.

Note: It was not possible to elaborate a posttreatment OS curve as all of the patients included in the study were originally treated in different centers in Italy.
Abbreviations: PFS, progression-free survival; OS, overall survival; 90Y-Dotatoc, 90Y-DOTA-Tyr3-octreotide; 177Lu-Dotatate, 177Lu-DOTA-Tyr3-octreotate.

ImhofABrunnerPMarincekNResponse, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancersJ Clin Oncol201129172416242321555692

 PubMed Web of Science ®Google Scholar

BushnellDLJrO’DorisioTMO’DorisioMS90Y-edotreotide for metastatic carcinoid refractory to octreotideJ Clin Oncol201028101652165920194865

 PubMed Web of Science ®Google Scholar

KwekkeboomDJde HerderWWKamBLTreatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0, Tyr3]octreotate: toxicity, efficacy, and survivalJ Clin Oncol200826132124213018445841

 PubMed Web of Science ®Google Scholar

EzziddinSAttassiMYong-HingCJPredictors of long-term outcome in patients with well-differentiated gastroenteropancreatic neuroendocrine tumors after peptide receptor radionuclide therapy with 177Lu-octreotateJ Nucl Med201455218319024434296

 PubMed Web of Science ®Google Scholar

GarkavijMNickelMSjorgreen-GleisnerK177Lu-[DOTA0,Tyr3] octreotate therapy in patients with disseminated neuroendrocrine tumors: Analysis of dosimetry with impact on future therapeutic strategyCancer20101164 Suppl1084109220127957

 PubMed Web of Science ®Google Scholar

SwärdCBernhardtPAhlmanH[177Lu-DOTA 0-Tyr 3]-octreotate treatment in patients with disseminated gastroenteropancreatic neuroendocrine tumors: the value of measuring absorbed dose to the kidneyWorld J Surg20103461368137220066413

 PubMed Web of Science ®Google Scholar

BodeiLCremonesiMGranaCMPeptide receptor radionuclide therapy with 177Lu-DOTATATE: the IEO phase I–II studyEur J Nucl Med Mol Imaging201138122125213521892623

 PubMed Web of Science ®Google Scholar

SeveriSSansoviniMIannielloAFeasibility and utility of re-treatment with 177Lu-DOTATATE in GEP-NENs relapsed after treatment with 90Y-DOTATOCEur J Nucl Med Mol Imaging201542131955196326112388

 PubMed Web of Science ®Google Scholar