Unexpectedly Durable Palliation of Metastatic Olfactory Neuroblastoma Using Anti-Angiogenic Therapy with Bevacizumab

Abstract

Olfactory neuroblastomas (ONBs) are rare malignant tumors that arise from olfactory epithelium and typically present with symptoms attributable to locally invasive disease. Kadish radiographic staging and Hyams' histopathologic grading are prognostic. Overall survival rates, averaging 60–70% at 5 years, remain limited by high rates of delayed loco-regional and distant progression. At initial presentation, the available evidence supports the use of multimodality therapy, historically surgery and radiation, to improve disease-free and overall survival. At recurrence/progression, the available evidence supports the use of therapy to improve disease control and symptoms (palliation), but patient heterogeneity dictates individualization of modalities. Although the ideal use of chemotherapy as a modality remains undefined, the available evidence supports it use, historically platinum-based, for palliation. However, recent insights into the molecular-genetic aberrations of ONBs, coupled with the emergence chemotherapeutic agents capable of targeting such aberrations, suggest an expanded role. The authors report a case of a 60 years-old man, heavily pre-treated for metastatic ONB, presenting with profound central-nerve-system and head-and-neck symptoms. He experienced unexpectedly durable palliation with Bevacizumab anti-angiogenic therapy. Additionally, he experienced localized palliation with an Ommaya reservoir. The authors review the literature regarding historical and emerging therapies for ONB to emphasize the needs for individualization and translational-clinical studies.

Genetic and molecular alterations in olfactory neuroblastoma: implications for pathogenesis, prognosis and treatment

“…Moreover, another druggable protein and key player in new vessel formation, VEGF, is up-regulated via Bcl-2 in ONB cells [27]. In line bevacizumab, an anti-angiogenic agent stabilized the disease in a case of metastatic ONB for 28 months [28]. …”

“…Durable response was observed on therapy with sunitinib mesylate [68, 72], cetuximab [68], imatinib mesylate [73], bevacizumab [28] and temozolomide [74]. However, except in this one case, choice of these drugs was not supported by studies on possible genetic changes responsible for response.…”

Of mice and men: olfactory neuroblastoma among animals and humans

“…Additionally, there was an increase of KPS from 80 to 90% and palliation of his fatigue, neuro‐cognitive deficits, aphasia and seizures. The patient was also able to discontinue dexamethasone . Another possible treatment option is temozolomide, an alkylating agent with significant activity against human malignant gliomas.…”

Comprehensive Genomic Profiling of Esthesioneuroblastoma Reveals Additional Treatment Options

“…Current multimodality nontargeted therapies for relapsed ENBs are of limited clinical benefit. The use of targeted systemic therapies is rare, but durable responses, predominantly stable disease, have been reported for sunitinib , sunitinib plus cetuximab , everolimus , imatinib , and bevacizumab .…”