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Avastin Scintigraphy in Surveillance of Bevacizumab Treatment in a Patient With Neurofibromatosis Type 2 A Case Report Michelle W.J. Versleijen, MD,* Berit M. Verbist, MD,Þ Jef J.S. Mulder, MD,þ Lioe-Fee de Geus-Oei, MD,* and Carla M.L. van Herpen, MD§ Abstract: A patient with neurofibromatosis type 2 (bilateral vestibular schwannomas) was treated with bevacizumab (anti-vascular endothelial growth factor [VEFG] monoclonal antibody). The left-sided tumor showed intense uptake on pretreatment 111In-bevacizumab scintigraphy, indicating VEGF production in the tumor, and no uptake 4 weeks later, demonstrating effective binding of nonradiolabeled bevacizumab to the VEGF produced in the tumor. The right-sided tumor showed no tracer uptake at any time point. Significant tumor volume reduction (assessed with MRI) and hearing improvement were observed on the left side. 111In-bevacizumab scintigraphy may be a promising upfront patient selection tool to identify patients who may benefit from expensive bevacizumab treatment. Key Words: neurofibromatosis type 2, bevacizumab, volume reduction
111
In, scintigraphy,
(Clin Nucl Med 2014;39: 277Y280) Received for publication April 3, 2013; revision accepted November 11, 2013. From the Departments of *Nuclear Medicine, †Radiology, ‡Ear Nose and Throat, and §Medical Oncology, Radboud University Medical Centre, Nijmegen, the Netherlands. Conflicts of interest and sources of funding: none declared. Reprints: Michelle W.J. Versleijen, MD, MSc, PhD, Radboud University Medical Centre, Nijmegen, Department of Nuclear Medicine, Route 757, Geert Grooteplein 10, 6525 GA Nijmegen, the Netherlands. E-mail: [email protected]. Copyright * 2014 by Lippincott Williams & Wilkins ISSN: 0363-9762/14/3903Y0277
Clinical Nuclear Medicine
& Volume 39, Number 3, March 2014
REFERENCES 1. Fong B, Barkhoudarian G, Pezeshkian P, et al. The molecular biology and novel treatments of vestibular schwannomas. J Neurosurg. 2011;115:906Y914. 2. Combs SE, Volk S, Schulz-Ertner D, et al. Management of acoustic neuromas with fractionated stereotactic radiotherapy (FSRT): long-term results in 106 patients treated in a single institution. Int J Radiat Oncol Biol Phys. 2005; 63:75Y81. 3. Samii M, Matthies C, Tatagiba M. Management of vestibular schwannomas (acoustic neuromas): auditory and facial nerve function after resection of 120 vestibular schwannomas in patients with neurofibromatosis 2. Neurosurgery. 1997;40:696Y705. 4. Goutagny S, Raymond E, Sterkers O, et al. Radiographic regression of cranial meningioma in a NF2 patient treated by bevacizumab. Ann Oncol. 2011;22: 990Y991. 5. Plotkin SR, Stemmer-Rachamimov AO, Barker FG, et al. Hearing improvement after bevacizumab in patients with neurofibromatosis type 2. N Engl J Med. 2009;36:358Y367. 6. Plotkin SR, Merker VL, Halpin C, et al. Bevacizumab for progressive vestibular schwannoma in neurofibromatosis type 2: a retrospective review of 31 patients. Otol Neurotol. 2012;33:1046Y1052. 7. Eminowicz GK, Raman R, Conibear J, et al. Bevacizumab treatment for vestibular schwannomas in neurofibromatosis type two: report of two cases, including responses after prior gamma knife and vascular endothelial growth factor inhibition therapy. J Laryngol Otol. 2012;126:79Y82. 8. Mautner VF, Nguyen R, Kutta H, et al. Bevacizumab induces regression of vestibular schwannomas in patients with neurofibromatosis type 2. Neuro Oncol. 2010;12:14Y18. Epub 2009 Oct 20.
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& Volume 39, Number 3, March 2014
FIGURE 1. A 53-year-old male patient with bilateral vestibular schwannomas related to neurofibromatosis type 2 (NF-2) presented with hearing problems that existed for more than 10 years that, besides from NF-2, could have been caused by previous noise exposure. The tone audiogram revealed an asymmetric perceptive hearing loss of 75 dB on the right and 83 dB on the left. The speech audiogram revealed a maximum speech reception threshold score of 14% at 110 dB and 11% at 120 dB on the left and of 27% at 110 dB and 55% at 120 dB on the right (A). Results of surgery and radiotherapy for vestibular schwannomas related to NF-2 seem worse than for sporadic vestibular schwannomas, and novel targeted therapies are being developed.1Y3 Our patient was treated with bevacizumab off-label (Avastin), an anti-vascular endothelial growth factor monoclonal antibody, 5 mg/kg of body weight intravenously every 2 weeks. A subjective hearing improvement and objectively improved speech reception on the left side occurred and persisted during the treatments (B and C, ie, after 8 and 11 treatments, respectively).
278
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* 2014 Lippincott Williams & Wilkins
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Clinical Nuclear Medicine
& Volume 39, Number 3, March 2014
Avastin Scintigraphy in Neurofibromatosis Type 2
FIGURE 2. Before the first treatment, an 111In-bevacizumab scintigraphy was performed. Seven days post-IV injection of 100 MBq (2.7 mCi) 111In-bevacizumab, cerebral scintigraphy showed intense focal radiopharmaceutical uptake, indicating vascular endothelial growth factor production, on the left-sided tumor (A). On the right side, no uptake was observed. Four weeks after the first treatment, a second bevacizumab scan showed that radiolabeled tracer uptake normalized at the left-sided schwannoma, indicating the binding of nonradiolabeled bevacizumab to the vascular endothelial growth factor produced in the tumor, whereas the right-sided tumor again showed no uptake (B).
* 2014 Lippincott Williams & Wilkins
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Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
279
Clinical Nuclear Medicine
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& Volume 39, Number 3, March 2014
FIGURE 3. Before the first treatment, cerebral MRI showed a vestibular schwannoma of 5.54 mL on the left and 1.19 mL on the right (A and B). After 3 and 9 treatments, tumor volumes decreased to 3.24 mL and 2.67 mL (ie, 52% volume reduction) on the left and 0.96 mL and 0.88 mL on the right, respectively (C). Comparable results (ie, tumor volume reduction mainly on the largest sized tumors) have been described by others.4 Because of persistent problematic wound healing on the ankle and fever, the patient was eventually withdrawn from bevacizumab treatment after 13 administrations in a period of 7 months. As observed in previous studies, the subjective hearing loss increased in the following 4 months in which the patient was not treated because of persisting wound problems.5,6 This was not confirmed by an audiogram because the patient did not show at further clinical follow-up. Tumor volume reduction and hearing improvement after bevacizumab treatment have been described by others.5Y8 This report is the first that shows a possible correlation between effective binding of bevacizumab to the vascular endothelial growth factor produced in vestibular schwannomas associated with NF-2, indicated by decrease radiolabeled bevacizumab uptake after nonradiolabeled bevacizumab treatment, and significant treatment effects on the same side. The present data suggest that 111In-bevacizumab scintigraphy is a promising upfront selection tool that potentially can identify those patients who may benefit from expensive bevacizumab treatment.
280
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* 2014 Lippincott Williams & Wilkins
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Avastin Scintigraphy in Surveillance of Bevacizumab Treatment in a Patient With Neurofibromatosis Type 2 A Case Report Michelle W.J. Versleijen, MD,* Berit M. Verbist, MD,Þ Jef J.S. Mulder, MD,þ Lioe-Fee de Geus-Oei, MD,* and Carla M.L. van Herpen, MD§ Abstract: A patient with neurofibromatosis type 2 (bilateral vestibular schwannomas) was treated with bevacizumab (anti-vascular endothelial growth factor [VEFG] monoclonal antibody). The left-sided tumor showed intense uptake on pretreatment 111In-bevacizumab scintigraphy, indicating VEGF production in the tumor, and no uptake 4 weeks later, demonstrating effective binding of nonradiolabeled bevacizumab to the VEGF produced in the tumor. The right-sided tumor showed no tracer uptake at any time point. Significant tumor volume reduction (assessed with MRI) and hearing improvement were observed on the left side. 111In-bevacizumab scintigraphy may be a promising upfront patient selection tool to identify patients who may benefit from expensive bevacizumab treatment. Key Words: neurofibromatosis type 2, bevacizumab, volume reduction
111
In, scintigraphy,
(Clin Nucl Med 2014;39: 277Y280) Received for publication April 3, 2013; revision accepted November 11, 2013. From the Departments of *Nuclear Medicine, †Radiology, ‡Ear Nose and Throat, and §Medical Oncology, Radboud University Medical Centre, Nijmegen, the Netherlands. Conflicts of interest and sources of funding: none declared. Reprints: Michelle W.J. Versleijen, MD, MSc, PhD, Radboud University Medical Centre, Nijmegen, Department of Nuclear Medicine, Route 757, Geert Grooteplein 10, 6525 GA Nijmegen, the Netherlands. E-mail: [email protected]. Copyright * 2014 by Lippincott Williams & Wilkins ISSN: 0363-9762/14/3903Y0277
Clinical Nuclear Medicine
& Volume 39, Number 3, March 2014
REFERENCES 1. Fong B, Barkhoudarian G, Pezeshkian P, et al. The molecular biology and novel treatments of vestibular schwannomas. J Neurosurg. 2011;115:906Y914. 2. Combs SE, Volk S, Schulz-Ertner D, et al. Management of acoustic neuromas with fractionated stereotactic radiotherapy (FSRT): long-term results in 106 patients treated in a single institution. Int J Radiat Oncol Biol Phys. 2005; 63:75Y81. 3. Samii M, Matthies C, Tatagiba M. Management of vestibular schwannomas (acoustic neuromas): auditory and facial nerve function after resection of 120 vestibular schwannomas in patients with neurofibromatosis 2. Neurosurgery. 1997;40:696Y705. 4. Goutagny S, Raymond E, Sterkers O, et al. Radiographic regression of cranial meningioma in a NF2 patient treated by bevacizumab. Ann Oncol. 2011;22: 990Y991. 5. Plotkin SR, Stemmer-Rachamimov AO, Barker FG, et al. Hearing improvement after bevacizumab in patients with neurofibromatosis type 2. N Engl J Med. 2009;36:358Y367. 6. Plotkin SR, Merker VL, Halpin C, et al. Bevacizumab for progressive vestibular schwannoma in neurofibromatosis type 2: a retrospective review of 31 patients. Otol Neurotol. 2012;33:1046Y1052. 7. Eminowicz GK, Raman R, Conibear J, et al. Bevacizumab treatment for vestibular schwannomas in neurofibromatosis type two: report of two cases, including responses after prior gamma knife and vascular endothelial growth factor inhibition therapy. J Laryngol Otol. 2012;126:79Y82. 8. Mautner VF, Nguyen R, Kutta H, et al. Bevacizumab induces regression of vestibular schwannomas in patients with neurofibromatosis type 2. Neuro Oncol. 2010;12:14Y18. Epub 2009 Oct 20.
www.nuclearmed.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
277
Clinical Nuclear Medicine
Versleijen et al
& Volume 39, Number 3, March 2014
FIGURE 1. A 53-year-old male patient with bilateral vestibular schwannomas related to neurofibromatosis type 2 (NF-2) presented with hearing problems that existed for more than 10 years that, besides from NF-2, could have been caused by previous noise exposure. The tone audiogram revealed an asymmetric perceptive hearing loss of 75 dB on the right and 83 dB on the left. The speech audiogram revealed a maximum speech reception threshold score of 14% at 110 dB and 11% at 120 dB on the left and of 27% at 110 dB and 55% at 120 dB on the right (A). Results of surgery and radiotherapy for vestibular schwannomas related to NF-2 seem worse than for sporadic vestibular schwannomas, and novel targeted therapies are being developed.1Y3 Our patient was treated with bevacizumab off-label (Avastin), an anti-vascular endothelial growth factor monoclonal antibody, 5 mg/kg of body weight intravenously every 2 weeks. A subjective hearing improvement and objectively improved speech reception on the left side occurred and persisted during the treatments (B and C, ie, after 8 and 11 treatments, respectively).
278
www.nuclearmed.com
* 2014 Lippincott Williams & Wilkins
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Clinical Nuclear Medicine
& Volume 39, Number 3, March 2014
Avastin Scintigraphy in Neurofibromatosis Type 2
FIGURE 2. Before the first treatment, an 111In-bevacizumab scintigraphy was performed. Seven days post-IV injection of 100 MBq (2.7 mCi) 111In-bevacizumab, cerebral scintigraphy showed intense focal radiopharmaceutical uptake, indicating vascular endothelial growth factor production, on the left-sided tumor (A). On the right side, no uptake was observed. Four weeks after the first treatment, a second bevacizumab scan showed that radiolabeled tracer uptake normalized at the left-sided schwannoma, indicating the binding of nonradiolabeled bevacizumab to the vascular endothelial growth factor produced in the tumor, whereas the right-sided tumor again showed no uptake (B).
* 2014 Lippincott Williams & Wilkins
www.nuclearmed.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
279
Clinical Nuclear Medicine
Versleijen et al
& Volume 39, Number 3, March 2014
FIGURE 3. Before the first treatment, cerebral MRI showed a vestibular schwannoma of 5.54 mL on the left and 1.19 mL on the right (A and B). After 3 and 9 treatments, tumor volumes decreased to 3.24 mL and 2.67 mL (ie, 52% volume reduction) on the left and 0.96 mL and 0.88 mL on the right, respectively (C). Comparable results (ie, tumor volume reduction mainly on the largest sized tumors) have been described by others.4 Because of persistent problematic wound healing on the ankle and fever, the patient was eventually withdrawn from bevacizumab treatment after 13 administrations in a period of 7 months. As observed in previous studies, the subjective hearing loss increased in the following 4 months in which the patient was not treated because of persisting wound problems.5,6 This was not confirmed by an audiogram because the patient did not show at further clinical follow-up. Tumor volume reduction and hearing improvement after bevacizumab treatment have been described by others.5Y8 This report is the first that shows a possible correlation between effective binding of bevacizumab to the vascular endothelial growth factor produced in vestibular schwannomas associated with NF-2, indicated by decrease radiolabeled bevacizumab uptake after nonradiolabeled bevacizumab treatment, and significant treatment effects on the same side. The present data suggest that 111In-bevacizumab scintigraphy is a promising upfront selection tool that potentially can identify those patients who may benefit from expensive bevacizumab treatment.
280
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* 2014 Lippincott Williams & Wilkins
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
