PURPOSE: Increasing evidence supports the value of peptide receptor radionuclide therapy (PRRT) in patients with metastatic neuroendocrine tumours (NET), but there are limited data on its specific efficacy in NET of small intestinal (midgut) origin. This study aims to define the benefit of PRRT with (177)Lu-octreotate for this circumscribed entity derived by a uniformly treated patient cohort. METHODS: A total of 61 consecutive patients with unresectable, advanced small intestinal NET G1-2 stage IV treated with (177)Lu-octreotate (4 intended cycles at 3-month intervals, mean activity per cycle 7.9 GBq) were analysed. Sufficient tumour uptake on baseline receptor imaging and either documented tumour progression (n = 46) or uncontrolled symptoms (n = 15) were prerequisites for treatment. Response was evaluated according to modified Southwest Oncology Group (SWOG) criteria and additionally with Response Criteria in Solid Tumors (RECIST) 1.1. Assessment of survival was performed using Kaplan-Meier curves and Cox proportional hazards model for uni- and multivariate analyses. Toxicity was assessed according to standardized follow-up laboratory work-up including blood counts, liver and renal function, supplemented with serial (99m)Tc-diethylenetriaminepentaacetic acid (DTPA) clearance measurements. RESULTS: The median follow-up period was 62 months. Reversible haematotoxicity (≥ grade 3) occurred in five patients (8.2%). No significant nephrotoxicity (≥ grade 3) was observed. Treatment response according to modified SWOG criteria consisted of partial response in 8 (13.1%), minor response in 19 (31.1%), stable disease in 29 (47.5%) and progressive disease in 5 (8.2%) patients. The disease control rate was 91.8%. Median progression-free survival (PFS) and overall survival (OS) was 33 [95% confidence interval (CI) 25-41] and 61 months (95% CI NA), respectively. Objective response was associated with longer survival (p = 0.005). Independent predictors of shorter PFS were functionality [hazard ratio (HR) 2.1, 95% CI 1.0-4.5, p = 0.05] and high plasma chromogranin A (CgA) levels > 600 ng/ml (HR 2.9, 95% CI 1.5-5.5, p < 0.001) at baseline. CONCLUSION: PRRT is well tolerated and very effective in advanced well-differentiated small intestinal (midgut) NET. A high disease control rate and long PFS can be achieved with this modality after failure of standard biotherapy with somatostatin analogues. Tumour functionality and high plasma CgA appear to be independent predictors of unfavourable patient outcome.
PURPOSE: Increasing evidence supports the value of peptide receptor radionuclide therapy (PRRT) in patients with metastatic neuroendocrine tumours (NET), but there are limited data on its specific efficacy in NET of small intestinal (midgut) origin. This study aims to define the benefit of PRRT with (177)Lu-octreotate for this circumscribed entity derived by a uniformly treated patient cohort. METHODS: A total of 61 consecutive patients with unresectable, advanced small intestinal NET G1-2 stage IV treated with (177)Lu-octreotate (4 intended cycles at 3-month intervals, mean activity per cycle 7.9 GBq) were analysed. Sufficient tumour uptake on baseline receptor imaging and either documented tumour progression (n = 46) or uncontrolled symptoms (n = 15) were prerequisites for treatment. Response was evaluated according to modified Southwest Oncology Group (SWOG) criteria and additionally with Response Criteria in Solid Tumors (RECIST) 1.1. Assessment of survival was performed using Kaplan-Meier curves and Cox proportional hazards model for uni- and multivariate analyses. Toxicity was assessed according to standardized follow-up laboratory work-up including blood counts, liver and renal function, supplemented with serial (99m)Tc-diethylenetriaminepentaacetic acid (DTPA) clearance measurements. RESULTS: The median follow-up period was 62 months. Reversible haematotoxicity (≥ grade 3) occurred in five patients (8.2%). No significant nephrotoxicity (≥ grade 3) was observed. Treatment response according to modified SWOG criteria consisted of partial response in 8 (13.1%), minor response in 19 (31.1%), stable disease in 29 (47.5%) and progressive disease in 5 (8.2%) patients. The disease control rate was 91.8%. Median progression-free survival (PFS) and overall survival (OS) was 33 [95% confidence interval (CI) 25-41] and 61 months (95% CI NA), respectively. Objective response was associated with longer survival (p = 0.005). Independent predictors of shorter PFS were functionality [hazard ratio (HR) 2.1, 95% CI 1.0-4.5, p = 0.05] and high plasma chromogranin A (CgA) levels > 600 ng/ml (HR 2.9, 95% CI 1.5-5.5, p < 0.001) at baseline. CONCLUSION: PRRT is well tolerated and very effective in advanced well-differentiated small intestinal (midgut) NET. A high disease control rate and long PFS can be achieved with this modality after failure of standard biotherapy with somatostatin analogues. Tumour functionality and high plasma CgA appear to be independent predictors of unfavourable patient outcome.
Authors: Marianne Pavel; Eric Baudin; Anne Couvelard; Eric Krenning; Kjell Öberg; Thomas Steinmüller; Martin Anlauf; Bertram Wiedenmann; Ramon Salazar Journal: Neuroendocrinology Date: 2012-02-15 Impact factor: 4.914
Authors: Andreas Klaus Pfeifer; Tine Gregersen; Henning Grønbæk; Carsten Palnæs Hansen; Jan Müller-Brand; Karin Herskind Bruun; Klaus Krogh; Andreas Kjær; Ulrich Knigge Journal: Neuroendocrinology Date: 2011-02-19 Impact factor: 4.914
Authors: A Sabet; F Khalaf; C J Yong-Hing; A Sabet; T Haslerud; H Ahmadzadehfar; S Guhlke; F Grünwald; H-J Biersack; S Ezziddin Journal: Nuklearmedizin Date: 2014 Impact factor: 1.379
Authors: James C Yao; Alexandria T Phan; David Z Chang; Robert A Wolff; Kenneth Hess; Sanjay Gupta; Carmen Jacobs; Jeannette E Mares; Andrea N Landgraf; Asif Rashid; Funda Meric-Bernstam Journal: J Clin Oncol Date: 2008-09-10 Impact factor: 44.544
Authors: Ashley Kieran Clift; Omar Faiz; Adil Al-Nahhas; Andreas Bockisch; Marc Olaf Liedke; Erik Schloericke; Harpreet Wasan; John Martin; Paul Ziprin; Krishna Moorthy; Andrea Frilling Journal: J Gastrointest Surg Date: 2015-09-22 Impact factor: 3.452
Authors: Amir Sabet; Alexander R Haug; Collin Eiden; Christoph J Auernhammer; Birgit Simon; Peter Bartenstein; Hans J Biersack; Samer Ezziddin Journal: Am J Nucl Med Mol Imaging Date: 2017-04-15
Authors: Bryson W Katona; Giorgio A Roccaro; Michael C Soulen; Yu-Xiao Yang; Bonita J Bennett; Brian P Riff; Rebecca A Glynn; Damian Wild; Guillaume P Nicolas; Daniel A Pryma; Ursina R Teitelbaum; David C Metz Journal: Pancreas Date: 2017-10 Impact factor: 3.327
Authors: Giuseppe Lo Russo; Sara Pusceddu; Natalie Prinzi; Martina Imbimbo; Claudia Proto; Diego Signorelli; Milena Vitali; Monica Ganzinelli; Marco Maccauro; Roberto Buzzoni; Ettore Seregni; Filippo de Braud; Marina Chiara Garassino Journal: Tumour Biol Date: 2016-07-27
Authors: L Bodei; M Kidd; I M Modlin; S Severi; I Drozdov; S Nicolini; D J Kwekkeboom; E P Krenning; R P Baum; G Paganelli Journal: Eur J Nucl Med Mol Imaging Date: 2015-11-23 Impact factor: 9.236