Emily Vaughan1, Joseph Machta2, Martin Walker3, Christos Toumpanakis2, Martyn Caplin2, Shaunak Navalkissoor1. 1. 1 Department of Nuclear Medicine, Royal Free London NHS Foundation Trust , London , UK. 2. 2 Neuroendocrine Tumour Unit, Department of Gastroenterology, Royal Free London NHS Foundation Trust , London , UK. 3. 3 Department of Epidemiology, School of Public Health, Faculty of Medicine, Imperial College London , London , UK.
Abstract
OBJECTIVE: : To evaluate the efficacy and toxicity of a repeat peptide receptor radionuclide therapy (PRRT) course in neuroendocrine tumour patients who have progressed following previous PRRT and to identify factors contributing to retreatment outcomes. METHODS: : This was a retrospective analysis of 47 consecutive patients who had been treated with PRRT (PRRT1) and following disease progression were retreated with a second course of PRRT (PRRT2). We reviewed patient, tumour and treatment characteristics, time to progression after PRRT1 and PRRT2, overall survival and toxicity. We evaluated Kaplan-Meier survival plots, multiple regression analysis on factors predictive of time to progression and toxicity. RESULTS: : PRRT1: 45/47 patients were initially were treated with 90Y-DOTATATE, with two patients treated with 177Lu-DOTATATE. The median progression free survival (PFS) following PRRT1 was 30 months [95% confidence interval (CI) (26.9-36.6 months)]. Two patients developed Grade 1 renal toxicity. 3/47 patients had bone marrow toxicity, with 1 of these patients having Grade 3 toxicity. PRRT2: At the second course of treatment, 29 patients were treated with 90Y-DOTATATE and 18 patients with 177Lu-DOTATATE. Of the 44 patients with evaluable survival data, 41 patients developed disease progression. The median PFS after PRRT2 was 17.5 months [95% CI (11-23.8 months)]. There was no statistically significant difference in median PFS dependent on the choice of radiopharmaceutical: median PFS for 177Lu-DOTATATE = 17.2 months, median PFS for 90Y-DOTATATE = 17.3 months. Male sex and high burden of liver metastases were associated with shorter PFS following a PRRT retreatment course. 17/41 (41%) patients had bone marrow toxicity (2/17 had Grade 3 toxicity; no Grade 4 toxicity was seen). One patient developed myelodysplastic syndrome. 6/41 (14.6%) developed Grade 1 renal toxicity and 1/41 (2.4%) had Grade 4 renal toxicity. The median overall survival from commencement of first PRRT cycle was 71 months. CONCLUSION: : PRRT retreatment is safe and offers patients, who had progressed following initial PRRT course, a reasonably good PFS. Extra consideration is needed in patients with multiple comorbidities, as they may be at greater risk of renal and haematological toxicity. Male sex and high burden of liver metastases seem to be associated with shorter PFS following PRRT retreatment. ADVANCES IN KNOWLEDGE:: The majority of studies on PRRT have shown that it is effective as an initial treatment. This study with long-term follow-up demonstrates that PRRT is safe and effective retreatment option in patients that have progressed following initial PRRT course.
OBJECTIVE: : To evaluate the efficacy and toxicity of a repeat peptide receptor radionuclide therapy (PRRT) course in neuroendocrine tumourpatients who have progressed following previous PRRT and to identify factors contributing to retreatment outcomes. METHODS: : This was a retrospective analysis of 47 consecutive patients who had been treated with PRRT (PRRT1) and following disease progression were retreated with a second course of PRRT (PRRT2). We reviewed patient, tumour and treatment characteristics, time to progression after PRRT1 and PRRT2, overall survival and toxicity. We evaluated Kaplan-Meier survival plots, multiple regression analysis on factors predictive of time to progression and toxicity. RESULTS: : PRRT1: 45/47 patients were initially were treated with 90Y-DOTATATE, with two patients treated with 177Lu-DOTATATE. The median progression free survival (PFS) following PRRT1 was 30 months [95% confidence interval (CI) (26.9-36.6 months)]. Two patients developed Grade 1 renal toxicity. 3/47 patients had bone marrow toxicity, with 1 of these patients having Grade 3 toxicity. PRRT2: At the second course of treatment, 29 patients were treated with 90Y-DOTATATE and 18 patients with 177Lu-DOTATATE. Of the 44 patients with evaluable survival data, 41 patients developed disease progression. The median PFS after PRRT2 was 17.5 months [95% CI (11-23.8 months)]. There was no statistically significant difference in median PFS dependent on the choice of radiopharmaceutical: median PFS for 177Lu-DOTATATE = 17.2 months, median PFS for 90Y-DOTATATE = 17.3 months. Male sex and high burden of liver metastases were associated with shorter PFS following a PRRT retreatment course. 17/41 (41%) patients had bone marrow toxicity (2/17 had Grade 3 toxicity; no Grade 4 toxicity was seen). One patient developed myelodysplastic syndrome. 6/41 (14.6%) developed Grade 1 renal toxicity and 1/41 (2.4%) had Grade 4 renal toxicity. The median overall survival from commencement of first PRRT cycle was 71 months. CONCLUSION: : PRRT retreatment is safe and offers patients, who had progressed following initial PRRT course, a reasonably good PFS. Extra consideration is needed in patients with multiple comorbidities, as they may be at greater risk of renal and haematological toxicity. Male sex and high burden of liver metastases seem to be associated with shorter PFS following PRRT retreatment. ADVANCES IN KNOWLEDGE:: The majority of studies on PRRT have shown that it is effective as an initial treatment. This study with long-term follow-up demonstrates that PRRT is safe and effective retreatment option in patients that have progressed following initial PRRT course.
Authors: Thomas A Hope; Lisa Bodei; Jennifer A Chan; Ghassan El-Haddad; Nicholas Fidelman; Pamela L Kunz; Josh Mailman; Yusuf Menda; David C Metz; Erik S Mittra; Daniel A Pryma; Diane L Reidy-Lagunes; Simron Singh; Jonathan R Strosberg Journal: J Nucl Med Date: 2020-02 Impact factor: 11.082
Authors: Linn Hagmarker; Johanna Svensson; Tobias Rydén; Martijn van Essen; Anna Sundlöv; Katarina Sjögreen Gleisner; Peter Gjertsson; Peter Bernhardt Journal: J Nucl Med Date: 2019-03-22 Impact factor: 10.057
Authors: Anna Zemczak; Paweł Gut; Dariusz Pawlak; Maciej Kołodziej; Leszek Królicki; Beata Kos-Kudła; Marek Ruchała; Grzegorz Kamiński; Jolanta Kunikowska Journal: Int J Endocrinol Date: 2021-01-23 Impact factor: 3.257
Authors: Danny Feijtel; Gabriela N Doeswijk; Nicole S Verkaik; Joost C Haeck; Daniela Chicco; Carmelina Angotti; Mark W Konijnenberg; Marion de Jong; Julie Nonnekens Journal: Theranostics Date: 2021-01-01 Impact factor: 11.556
Authors: Elena María Vida Navas; Alberto Martínez Lorca; Aintzane Sancho Gutiérrez; Lucia Sanz Gómez; Teresa Navarro Martínez; Enrique Grande Pulido; Alfredo Carrato Mena; Pablo Gajate Borau Journal: Front Endocrinol (Lausanne) Date: 2021-04-15 Impact factor: 5.555
Authors: Martina T Mogl; Eva M Dobrindt; Josephine Buschermöhle; Claudia Bures; Johann Pratschke; Holger Amthauer; Christoph Wetz; Henning Jann Journal: Visc Med Date: 2020-01-20