Somatostatin-receptor-targeted radionuclide therapy for progressive meningioma: benefit linked to68Ga-DOTATATE/-TOC uptake

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Abstract

<div class="section"> <a class="named-anchor" id="d1486170e266">  </a> <h5 class="section-title" id="d1486170e267">Background</h5> <p id="d1486170e269">The prognosis of patients with progressive meningioma after failure of surgery and radiotherapy is poor. </p> </div><div class="section"> <a class="named-anchor" id="d1486170e271">  </a> <h5 class="section-title" id="d1486170e272">Methods</h5> <p id="d1486170e274">We retrospectively evaluated the safety and efficacy of somatostatin-receptor (SSTR)-targeted radionuclide therapy ( <sup>177</sup>Lu-DOTATATE [ <i>n</i> = 16], <sup>90</sup>Y-DOTATOC [ <i>n</i> = 3], or both [ <i>n</i> = 1]) in patients with progressive, treatment-refractory meningiomas (5 World Health Organization [WHO] grade I, 7 WHO grade II, 8 WHO grade III) and in part multifocal disease (17 of 20 patients). </p> </div><div class="section"> <a class="named-anchor" id="d1486170e291">  </a> <h5 class="section-title" id="d1486170e292">Results</h5> <p id="d1486170e294">SSTR radionuclide treatment (median of 3 treatment cycles, median administered dose/cycle 7400 MBq) led to a disease stabilization in 10 of 20 patients for a median time of 17 months. Stratification according to WHO grade showed a median progression-free survival (PFS) of 32.2 months for grade I tumors, 7.2 for grade II, and 2.1 for grade III. PFS at 6 months was 100% for grade I, 57% for grade II, and 0% for grade III. Median overall survival was 17.2 months in WHO grade III patients and not reached for WHO I and II at a median follow-up of 20 months. In the analysis of single meningioma lesions, maximal and mean standardized uptake values in pretherapeutic <sup>68</sup>Ga-DOTATOC/-TATE PET/CT were significantly higher in those lesions with radiographic stability after 6 months. In line with this, high expression of SSTR via immunohistochemistry was associated with PFS >6 months. </p> </div><div class="section"> <a class="named-anchor" id="d1486170e299">  </a> <h5 class="section-title" id="d1486170e300">Conclusions</h5> <p id="d1486170e302">SSTR-targeted radionuclide treatment has activity in a subset of patients with meningioma. Expression of SSTR via immunohistochemistry or radionuclide uptake might serve as a predictive biomarker for outcome to facilitate individualized treatment optimization in patients with uni- and multifocal meningiomas. </p> </div>

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Quinn Ostrom, Haley Gittleman, Jordonna Fulop … (2015)

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Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers.

Nicolas Marincek, Jan Müller, Beat A. Imhof … (2011)

To investigate response, survival, and safety profile of the somatostatin-based radiopeptide (90)yttrium-labeled tetraazacyclododecane-tetraacetic acid modified Tyr-octreotide ([(90)Y-DOTA]-TOC) in neuroendocrine cancers. In a clinical phase II single-center open-label trial, patients with neuroendocrine cancers were treated with repeated cycles of [(90)Y-DOTA]-TOC. Each cycle consisted of a single intravenous injection of 3.7GBq/m(2) body-surface [(90)Y-DOTA]-TOC. Additional cycles were withheld in case of tumor progression and/or permanent toxicity. Overall, 1,109 patients received 2,472 cycles of [(90)Y-DOTA]-TOC (median, two; range, one to 10 cycles per patient). Of the 1,109 patients, 378 (34.1%) experienced morphologic response; 172 (15.5%), biochemical response; and 329 (29.7%), clinical response. During a median follow-up of 23 months, 491 patients (44.3%) died. Longer survival was correlated with each: morphologic (hazard ratio [HR], 0.46; 95% CI, 0.38 to 0.56; median survival, 44.7 v 18.3 months; P < .001), biochemical (HR, 0.75; 95% CI, 0.59 to 0.96; 35.3 v 25.7 months; P = .023), and clinical response (HR, 0.68; 95% CI, 0.56 to 0.82; 36.8 v 23.5 months; P < .001). Overall, 142 patients (12.8%) developed grade 3 to 4 transient hematologic toxicities, and 103 patients (9.2%) experienced grade 4 to 5 permanent renal toxicity. Multivariable regression revealed that tumoral uptake in the initial imaging study was predictive for overall survival (HR, 0.45; 95% CI, 0.29 to 0.69; P < .001), whereas the initial kidney uptake was predictive for severe renal toxicity (HR, 1.59; 95% CI, 1.17 to 2.17; P = .003). This study documents the long-term outcome of [(90)Y-DOTA]-TOC treatment in a large cohort. Response to [(90)Y-DOTA]-TOC is associated with longer survival. Somatostatin receptor imaging is predictive for both survival after [(90)Y-DOTA]-TOC treatment and occurrence of renal toxicity.