Long-term results and tolerability of tandem peptide receptor radionuclide therapy with 90Y/177Lu-DOTATATE in neuroendocrine tumors with respect to the primary location: a 10-year study

Kunikowska, Jolanta; Pawlak, Dariusz; Bak, Marianna I; Kos–Kudła, Beata; Mikołajczak, Renata; Królicki, Leszek

doi:10.1007/s12149-017-1163-6

Cited by 52 publications

(41 citation statements)

References 21 publications

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“…The reported PFS in other studies (32-41 mo) is higher than in the current study (22 mo). Meanwhile, the OS (43 mo) of the current patient cohort was within the reported range in the literature (38-82 mo) (21)(22)(23)(24)(25)(26). However, differences between the current study and the literature exist.…”

Section: Discussionsupporting

confidence: 61%

“…These patients are known to have a better survival than patients with primary lung and colon NETs (27). Another study included only patients with G1/G2 tumors, who are likely to have a longer OS than patients with G3 tumors (24). In our study, high-risk patients with characteristics such as G3 tumors, WHO 2/3, and nongastroenteropancreatic NETs were also included.…”

Section: Discussionmentioning

confidence: 99%

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Parameters to Predict Progression-Free and Overall Survival After Peptide Receptor Radionuclide Therapy: A Multivariate Analysis in 782 Patients

et al. 2019

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Peptide receptor radionuclide therapy (PRRT) is an effective treatment for patients with neuroendocrine neoplasms. The aim of this study was to identify clinical and treatment parameters associated with progression-free survival (PFS) and overall survival (OS). Methods: All patients treated from October 2002 until March 2016 at the Zentralklinik Bad Berka with at least 3 administrations of PRRT (maximal interval of 6 mo between consecutive administrations) were included. Data were collected in 5 categories: general patient characteristics, tumor characteristics, prior treatments, radioisotope used for PRRT, and blood chemistry. Survival was analyzed using Kaplan-Meier curves. Univariate and multivariate Cox regression analyses were performed to identify parameters associated with PFS and OS. Results: In total, 782 patients were included, with a median follow-up of 36 mo. The median PFS and OS were 22 and 53 mo, respectively. Parameters associated with lower PFS in the multivariate analysis were a Ki-67 of more than 5%, previous treatment with interferon-α and chemotherapy, presence of diabetes, and chromogranin-A (CgA) levels higher than 336 μg/L. Parameters associated with lower OS were a Ki-67 of more than 10%, performance status of at least 1, previous chemotherapy and ablation, and CgA levels higher than 112 μg/L. Conclusion: Higher Ki-67 values, as well as higher CgA levels and previous chemotherapy, had a negative outcome on both PFS and OS. Furthermore, PFS was negatively associated with previous interferon-α treatment and diabetes, whereas lower OS was related to prior ablation and higher performance status. http://jnm.snmjournals.org/content/60/9/1259 This article and updated information are available at: http://jnm.snmjournals.org/site/subscriptions/online.xhtml Information about subscriptions to JNM can be found at: http://jnm.snmjournals.org/site/misc/permission.xhtml

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Parameters to Predict Progression-Free and Overall Survival After Peptide Receptor Radionuclide Therapy: A Multivariate Analysis in 782 Patients

et al. 2019

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“…However, one should also bear in mind that the choice of radiopharmaceutical used for the initial treatment regime in our patient population was largely related to the size of the individual tumor lesion as depicted by PET/CT. Considering the complex situation including also the tumor dose and volume in different-sized lesions (29), the present analysis should be cautiously interpreted; combined use with 90 Y/ 177 Lu-DOTATATE was basically found to be highly effective, safe and showed similar results (30,31).…”

Section: Discussionmentioning

confidence: 79%

Twelve-Year Follow-up After Peptide Receptor Radionuclide Therapy

et al. 2018

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Peptide receptor radionuclide therapy (PRRT) has been used for more than twenty years as a systemic treatment approach in inoperable or metastatic somatostatin receptor (SSTR)-positive tumors. The purpose of this study was to analyze the long-term outcome of PRRT with regard to the most commonly used radiopharmaceuticals, Y-DOTA-Tyr3-octreotide (Y-DOTA-TOC) and Lu-DOTA-Tyr3-octreotate (Lu-DOTA-TATE). This retrospective clinical study included a total of 44 consecutive patients (27 men) with advanced tumors and enhanced SSTR expression. Mean age at initial diagnosis was 60 years (SD 11.3, range 40 to 84 years). Median follow-up was 80 months. In the mean 5.3 ± 2.5 cycles were administered forLu-PRRT with mean activity of 27.2 ± 14.9 GBq per patient and 5.5 ± 2.6 cycles for Y-PRRT with mean activity of 14.7 ± 7.3 GBq. Overall, 378 cycles were administered (mean 8.6 ± 3.4 cycles per patient) with an overall cumulative activity of 1514.1 GBq. Median overall survival (OS) was 79 months. Twenty-one (77.8%) of the 27 men and nine (52.9%) of the 17 women had died 12 years after commencement of PRRT. Shortest duration of illness was eight months, longest 155 months. Severe side-effects (WHO Grades III and IV) are seen in nine of the 14 patients still alive. Chronic kidney disease in combination with anemia is the most common finding in the nine patients with severe side-effects. Very poor prognosis was found for those patients who showed progressive disease (PD) in comparison with patients with cumulative disease control after initial PRRT (log-rank, p<0.001), while women and patients with no more than two tumor sites seem to especially benefit from PRRT not reaching significance levels. PRRT is very encouraging in terms of long-term outcome. Thirty-two percent (14/44 patients) of the patients with metastatic or inoperable disease are still alive more than 12 years after the beginning of radionuclide therapy. Possible predictors for favourable outcome are initial response to PRRT, number of affected sites and female gender.

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“…3 The two most commonly utilized radionuclides are 90 Yttrium ( 90 Y) and 177 Lutetium ( 177 Lu), and PRRT has been shown to be effective in the treatment of NETs. 4–12 The recent NETTER-1 trial compared patients with well-differentiated, metastatic, mid-gut neuroendocrine tumors who were treated with 177 Lu-Dotatate plus octreotide long-acting repeatable (LAR) versus octreotide LAR alone. 13 Progression-free survival (PFS) at month 20 was 65.2% in the 177 Lu-Dotatate group compared to 10.8% in the octreotide LAR alone group, supporting the effectiveness of PRRT for the treatment of well-differentiated mid-gut NETs.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Peptide Receptor Radionuclide Therapy in a United States–Based Cohort of Metastatic Neuroendocrine Tumor Patients

Katona¹,

Roccaro²,

Soulen³

et al. 2017

Pancreas

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Objectives Retrospective cohort study of a United States based-group of metastatic neuroendocrine tumor (NET) patients who underwent peptide receptor radionuclide therapy (PRRT). Methods Twenty-eight patients from a single United States NET Center were treated with PRRT. Toxicities were assessed using CTCAE v4.03. Progression was determined by RECIST 1.1. Univariate and multivariate Cox regression was performed to identify potential predictors of progression free survival (PFS) and overall survival (OS). Results The median age of NET diagnosis was 56 years, 50% of the patients were male, 46% of NET primaries were located in the pancreas, 71% of tumors were non-functional, 25% were WHO grade III, and 20% had at least a 25% hepatic tumor burden. Anemia (36%) was the most common post-PRRT toxicity, followed by leukopenia (31%), nephrotoxicity (27%), and thrombocytopenia (24%). Median PFS was 18 months, and median OS was 38 months. Having a WHO grade III NET or receiving systemic chemotherapy prior to PRRT where found to be to independent predictors of shorter PFS and OS. Conclusions PRRT is an effective therapy in a United States population. PFS and OS were better in WHO grade I/II NETs and when PRRT was sequenced prior to systemic chemotherapy.

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Long-term results and tolerability of tandem peptide receptor radionuclide therapy with 90Y/177Lu-DOTATATE in neuroendocrine tumors with respect to the primary location: a 10-year study

Abstract: These results indicated the tandem Y/Lu-DOTATATE therapy for patients with disseminated/inoperable NET as highly effective and safe, considering long-term side effects. In the majority of patients, clinical improvement was observed.

Cited by 52 publications

References 21 publications

Parameters to Predict Progression-Free and Overall Survival After Peptide Receptor Radionuclide Therapy: A Multivariate Analysis in 782 Patients

Parameters to Predict Progression-Free and Overall Survival After Peptide Receptor Radionuclide Therapy: A Multivariate Analysis in 782 Patients

Twelve-Year Follow-up After Peptide Receptor Radionuclide Therapy

Efficacy of Peptide Receptor Radionuclide Therapy in a United States–Based Cohort of Metastatic Neuroendocrine Tumor Patients

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