Individualized peptide-related-radionuclide-therapy concept using different radiolabelled somatostatin analogs in advanced cancer patients.
OBJECTIVE
Over the last decade, somatostatin (SST) receptor (R)-positive tumors have been treated using either (90)Y-DOTA-TOC, (177)Lu-DOTA-TATE or (90)Y-DOTA-LAN/(177)Lu-DOTA-LAN, at the Innsbruck Medical University. This report presents data from the evaluation of the initial 100 patients receiving receptor mediated radionuclide therapy (PRRT) according to our protocol.


METHODS
One-hundred patients with SSTR-positive tumors were treated (36 female, 64 male; mean age, 58 years; range, 13 to 84 years), including 68 patients with neuroendocrine tumors (NET), and patients with other non-neuroendocrine tumors, e.g. patients with radioiodine-negative thyroid carcinoma, refractory to conventional treatment modalities. Patients were selected based on high SSTR expression as assessed by (68)Ga-DOTA-TOC as first choice tracer for patients with NET, or (68)Ga-DOTA-LAN for patients with other tumor entities, or if the (68)Ga-DOTA-TOC PET was negative. Following positron emission tomography (PET), individual dosimetry was regularly performed using (111)In-labeled compounds. Therapy cycles were repeated every 10 weeks using either (90)Y-DOTA-TOC (3.7 GBq, 3-5 cycles) or (177)Lu-DOTA-TATE (7.4 GBq, 3-4 cycles). Thirteen patients received both and 5 patients even 3 different therapeutic compounds. Each patient received an amino acid solution (arginin, lysine) to reduce the kidney dose. Between the radioactive cycles a long-acting SST analog was applied. Dosages were individually adapted depending on several disease related factors.


RESULTS
Overall, following PRRT partial remission (PR) was observed in 23 patients (23 %), minor remission (MR) in 10 (10 %), stable disease (SD) in 42 patients (42 %). Although 25 patients (25 %) showed progressive disease (PD), palliative care was provided in most of these patients. In the group treated with 90Y-DOTA-TOC, 12 patients showed PR, 3 MR, 32 SD and 13 had PD. In the group of patients treated with (177)Lu-DOTA-TATE, PR was observed in 15 patients, MR in 8, SD in 19 and PD in 13 patients. Severe side effects (WHO Grad 3 and 4) were seen in only 6 % of patients. Severe long-term nephrotoxicity was observed in none of the patients. These adverse reactions were especially seen in patients who were treated with high doses per cycle, in patients pre-treated with chemotherapy and in patients with low clinical performance.


CONCLUSIONS
PRRT with differently labelled tracers (Y-90 or Lu-177) and different SST-analogs is generally well tolerated without serious side effects. These results favour the combined use of radiolabeled SST analogs providing a customized tumour targeting for size reduction and improvement of quality-of-life. Extended time intervals and reduced individual doses make sense in patients with advanced tumor stages, in case of moderate SSTR-expression, and in patients with higher age.
Gabriel
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Department of Nuclear Medicine, Innsbruck Medical University, Innsbruck, Austria. michael.gabriel@i-med.ac.at
Andergassen
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Putzer
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Kroiss
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Waitz
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Von Guggenberg
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Kendler
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Virgolini
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D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007553:Isotope Labeling; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D049268:Positron-Emission Tomography; D057285:Precision Medicine / Q000379:methods*; D017481:Receptors, Somatostatin / Q000378:metabolism; D013004:Somatostatin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
D017481:Receptors, Somatostatin; D013004:Somatostatin