Three‐year recurrence‐free survival in a patient with recurrent medulloblastoma after resection, high‐dose chemotherapy, and intrathecal Yttrium‐90‐labeled DOTA⁰‐D‐Phe¹‐Tyr³‐octreotide radiopeptide brachytherapy

Abstract

BACKGROUND Most medulloblastomas express high levels of somatostatin type 2 receptors (sst2). DOTA0‐D‐Phe1‐Tyr3‐octreotide (DOTATOC) specifically binds sst2 in the low nanomolar range. The cytotoxic effect is mediated by the chelated, β‐emitting, metallic radionuclide Yttrium 90 (90Y). The authors applied this innovative treatment option in a boy age 8 years who presented with a recurrent medulloblastoma of the cauda equina: a prognostically poor condition. Targeted radiotherapy was administered to treat minimal sst2‐expressing tumor remnants, which persisted despite conventional and high‐dose chemotherapy and intercurrent resection of the lesion. METHODS A medulloblastoma arising from the floor of the fourth ventricle had been removed surgically; then, the patient was treated with standard adjuvant chemotherapy and craniospinal irradiation according to the prospective HIT '91 protocol. Complete remission was achieved for 20 months, when a drop metastasis of the cauda equina manifested with sensorimotor lumbosacral deficits and urinary incontinence. After four cycles of neoadjuvant chemotherapy (which consisted of combined ifosfamide, carboplatinum and etoposide), two cycles of high‐dose chemotherapy and autologous stem cell transplantation were performed; in between, the responding residual tumor within the lumbosacral nerve fibers was microscopically removed. Thereafter, an Indium‐111‐DOTATOC test injection indicated sst2‐expressing tumor remnants within the cauda equina. Con‐ sequently, 4 cycles of [90Y]‐DOTATOC (4 × 562.5 megabecquerels) were injected directly into the cerebrospinal fluid in monthly intervals. RESULTS The consolidating intrathecal brachytherapy using [90Y]‐DOTATOC was tolerated well. A complete remission was achieved for a 3‐year period. The only remaining deficit was urinary incontinence. CONCLUSIONS Intrathecal administration of targeted radiopeptide brachytherapy in combination with conventional and high‐dose chemotherapy and surgical removal represents a promising new option to treat recurrent medulloblastoma and should be explored further. Cancer 2005. © 2005 American Cancer Society.

Quantitative Gene Expression of Somatostatin Receptors and Noradrenaline Transporter Underlying Scintigraphic Results in Patients with Neuroendocrine Tumors

“…The first clinical trials with such targeted radiotherapy have now been conducted. One of these protocols is based on DOTA- D -Phe 1 -Tyr 3 -DTPA-octreotide (DOTATOC) labeled with the beta-emitting radioisotope 90 Y [32, 33]. Another protocol is based on 177 Lu-DOTA⁰,Tyr 3 -octreotate and seems to be particularly valuable for the treatment of small tumors [34, 35].…”

Local Targeting of Malignant Gliomas by the Diffusible Peptidic Vector 1,4,7,10-Tetraazacyclododecane-1-Glutaric Acid-4,7,10-Triacetic Acid-Substance P

“…Toxin-delivering conjugates have to target every single tumor cell; radionuclide-based approaches can eliminate receptornegative tumor cells and cells not directly targeted by the drug through the range-dependent ''cross-fire'' effect. Most protocols for targeted local therapy of malignant brain tumors administer macromolecular compounds given by convection-enhanced delivery to improve biodistribution (13) (19,20), relapsing medulloblastoma (21), and SSTR2-positive gliomas (22)]. However, inconsistent expression of SSTR2 limited application in glioblastoma.…”

111In-Pentetreotide scintigraphy in medulloblastoma: A comparison with magnetic resonance imaging

“…However, this the first study in which the SRS and MRI findings were evaluated during the follow-up period per-lesion basis. In view of potential adjuvant treatment via somatostatin receptor mediated targeted radiotherapy [9], somatostatin receptor scintigraphy (SRS) was performed in addition to MRI. For the purpose of this retrospective study, we analyzed the results of both imaging studies in order to investigate the potential diagnostic role of 111 In-pentetreotide scintigraphy in the follow-up of medulloblastoma as compared to MRI.…”