Efficacy of peptide receptor radionuclide therapy for esthesioneuroblastoma, the Peter MacCallum Cancer Centre experience

Objectives: Esthesioneuroblastoma (ENB), also known as olfac­tory neuroblastoma, is a rare malignant sinonasal neoplasm accounting for 3% of all nasal cavity tumors. There is no consensus on standardized treatment strategy, common practice being surgical resection and adjuvant radio­therapy with or without chemotherapy depending on disease stage and clinical status. ENB commonly expresses somatostatin receptors (SSTR), allowing therapeutic targeting with peptide receptor radionuclide therapy (PRRT). Data on PRRT in ENB are significantly lacking with only few individual case reports in the literature. We reviewed the outcomes of patients with unresectable relapsed ENB despite prior conventional treatments, and subsequently treated with PRRT at our centre.

Methods: We retrospectively reviewed the medical records and imaging scans of five patients (3 men and 2 women age range 45-79 years), who were referred to The Peter McCallum Cancer Centre from August 2004 till November 2018, with a history of ENB treated with PRRT. All had high SSTR expression, demonstrated by intense uptake in Gallium-68 DOATATATE scan, defined as greater than normal background liver activity. They were treated with PRRT in variable combinations of Indium-111 Octreotate (In-Tate), Lu-177 DOTATATE (Lu-Tate), and Y-90 DOTATATE (Y-Tate). Median cumulative activity was 13.9 GBq In-Tate, 24.9 GBq Lu-Tate, and 2.7 GBq Y-Tate; with a median of 4 cycles. All patients had concomitant radiosensitising chemotherapy with at least one therapy cycle. We assessed the clinical outcome, in addition to anatomic and functional imaging changes and hematologic toxicity (CTCAE 4.1 criteria) post PRRT.

Results: Of these 5 patients, 3 had large volume disease, either locally extensive or widespread metastases; and 2 had small volume metastatic disease. At 3 months post induction PRRT, the disease control rate was 80%: 3 patients had partial imaging response on SSTR imaging, 1 patient had stabilization of previously progressive disease, and 1 patient who had retropharyngeal nodal disease with prior external beam radiation therapy had early progression after PRRT. Most patients who responded or stabilized by imaging, has concordant symptomatic improvement after PRRT.Three patients have died with overall survival ranging from 4-53 months (median 38 months) from the first PRRT cycle. The progression free survival ranged from 0-30 months (median 17 months). Two patients are still alive and being followed up. Side effects of PRRT include: 1 patient had grade 4 neutropenia, 1 had grade 2 thrombocytopenia, likely multifactorial related to combined and previous complex therapy regimens. One patient developed progressive surgery-related CSF leak, in the context of significant tumor regression after PRRT.

Conclusions: This series represents the largest case series of recurrent/metastatic ENB treated with PRRT. Our experience suggests that PRRT is feasible and can be an effective option in patients with unresectable locally extensive or metastatic ENB. Careful patient selection based on symptoms, imaging phenotype, disease volume and prior interventions may be factors that contribute to better outcomes. Given the rarity of the condition, ideally multi-centre prospective trials of PRRT in ENB are required to objectively assess disease control, quality of life and survival.

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