Twelve-Year Follow-up After Peptide Receptor Radionuclide Therapy

Abstract

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.

Long-term results of multimodal peptide receptor radionuclide therapy and fractionated external beam radiotherapy for treatment of advanced symptomatic meningioma

“…As expected, no relevant hematologic or renal toxicity was caused by the addition of one cycle of PRRT. Thus, our findings are in line with current literature on the safety of PRRT (especially when performed with 177 Lu) in patients suffering from meningioma [6,13] or neuroendocrine tumors [14,15].…”

Overview of Radiolabeled Somatostatin Analogs for Cancer Imaging and Therapy

“…With the perspective of several years of clinical use, PRRT with 90 Y-labeled somatostatin analogs appears to be well-tolerated with favorable long-term outcome. Unfortunately, Phase III studies are still lacking [ 164 , 165 ].…”

Molecular imaging and radionuclide therapy of pheochromocytoma and paraganglioma in the era of genomic characterization of disease subgroups

“…The main predictors of poor OS outcome after PRRT are non-specific and include high Ki-67 index (greater than 10%), high uptake on 18 F-FDG, involvement of more than two organ systems, local vs distant metastases, low Karnofsky performance score (≤70%), high tumor burden, identified progressive disease after first PRRT, and when PRRT is delivered as salvage therapy after chemotherapy (Delpassand et al 2014, Bodei et al 2015b, Kesavan & Turner 2016, Gabriel et al 2019, Wolf et al 2019. In another study, highly elevated maximum standardized uptake values (SUV max ) on pre-therapeutic 68 Ga-DOTATOC were associated with tumor shrinkage, reduction of tumor markers, and improved overall clinical…”