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Published in: Pituitary 6/2014

01-12-2014

Peptide receptor radionuclide therapy for aggressive atypical pituitary adenoma/carcinoma: variable clinical response in preliminary evaluation

Authors: Jillian Maclean, Matthew Aldridge, Jamshed Bomanji, Susan Short, Naomi Fersht

Published in: Pituitary | Issue 6/2014

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Abstract

Purpose

There are limited treatment options for progressive atypical pituitary adenomas and carcinomas. Peptide receptor radionuclide therapy that targets somatostatin receptors has recently been proposed as a potential treatment option. The theoretical rationale for efficacy is elegant but evaluation of outcomes in the first patients treated for this indication is required to assess whether further study is warranted.

Methods

We performed a case review of the three pituitary patients we have treated with 177Lutetium DOTATATE in our institution (two atypical adenomas, one carcinoma) and dosimetric analysis of the radiation uptake in one patient.

Results

Treatment was well tolerated. One patient with slowly progressive pituitary carcinoma has stable disease 40 months after completing the planned 4 cycles of treatment. Two patients with rapidly progressive atypical adenomas terminated treatment early due to continued disease progression. Dosimetric evaluation revealed inhomogenous uptake across the tumour (1.3–11.9 Gy with one cycle).

Conclusion

We have found mixed results in our first 3 patients with stable disease achieved only in the patient with the more slowly progressive tumour. As only a limited number of centres offer Peptide receptor radionuclide therapy, a formal study with prospective data collection may be feasible and if carried out should include dosimetric evaluation of absorbed dose.
Literature
1.
go back to reference Saeger W, Ludecke DK, Buchfelder M et al (2007) Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry. Eur J Endocrinol 156:203–216PubMedCrossRef Saeger W, Ludecke DK, Buchfelder M et al (2007) Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry. Eur J Endocrinol 156:203–216PubMedCrossRef
2.
go back to reference Zada G, Woodmansee WW, Ramkissoon S et al (2011) Atypical pituitary adenomas: incidence, clinical characteristics, and implications. J Neurosurg 114:336–344PubMedCrossRef Zada G, Woodmansee WW, Ramkissoon S et al (2011) Atypical pituitary adenomas: incidence, clinical characteristics, and implications. J Neurosurg 114:336–344PubMedCrossRef
3.
go back to reference Kaltsas GA, Nomikos P, Kontogeorgos G et al (2005) Clinical review: diagnosis and management of pituitary carcinomas. J Clin Endocrinol Metab 90:3089–3099PubMedCrossRef Kaltsas GA, Nomikos P, Kontogeorgos G et al (2005) Clinical review: diagnosis and management of pituitary carcinomas. J Clin Endocrinol Metab 90:3089–3099PubMedCrossRef
4.
go back to reference Lopes MB, Scheithauer BW, Schiff D (2005) Pituitary carcinoma: diagnosis and treatment. Endocrine 28:115–121PubMedCrossRef Lopes MB, Scheithauer BW, Schiff D (2005) Pituitary carcinoma: diagnosis and treatment. Endocrine 28:115–121PubMedCrossRef
5.
go back to reference Ortiz LD, Syro LV, Scheithauer BW et al (2012) Temozolomide in aggressive pituitary adenomas and carcinomas. Clinics (Sao Paulo) 67(Suppl 1):119–123CrossRef Ortiz LD, Syro LV, Scheithauer BW et al (2012) Temozolomide in aggressive pituitary adenomas and carcinomas. Clinics (Sao Paulo) 67(Suppl 1):119–123CrossRef
6.
go back to reference Kaltsas GA, Mukherjee JJ, Plowman PN et al (1998) The role of cytotoxic chemotherapy in the management of aggressive and malignant pituitary tumors. J Clin Endocrinol Metab 83:4233–4238PubMedCrossRef Kaltsas GA, Mukherjee JJ, Plowman PN et al (1998) The role of cytotoxic chemotherapy in the management of aggressive and malignant pituitary tumors. J Clin Endocrinol Metab 83:4233–4238PubMedCrossRef
7.
go back to reference Colao A, Grasso LF, Pivonello R et al (2011) Therapy of aggressive pituitary tumors. Expert Opin Pharmacother 12:1561–1570PubMedCrossRef Colao A, Grasso LF, Pivonello R et al (2011) Therapy of aggressive pituitary tumors. Expert Opin Pharmacother 12:1561–1570PubMedCrossRef
8.
go back to reference Laws ER Jr, Morris AM, Maartens N (2003) Gliadel for pituitary adenomas and craniopharyngiomas. Neurosurgery 53:255–269 discussion 259–260PubMedCrossRef Laws ER Jr, Morris AM, Maartens N (2003) Gliadel for pituitary adenomas and craniopharyngiomas. Neurosurgery 53:255–269 discussion 259–260PubMedCrossRef
9.
go back to reference Ortiz LD, Syro LV, Scheithauer BW et al (2012) Anti-VEGF therapy in pituitary carcinoma. Pituitary 15:445–449PubMedCrossRef Ortiz LD, Syro LV, Scheithauer BW et al (2012) Anti-VEGF therapy in pituitary carcinoma. Pituitary 15:445–449PubMedCrossRef
10.
go back to reference Ramirez C, Cheng S, Vargas G et al (2012) Expression of Ki-67, PTTG1, FGFR4, and SSTR 2, 3, and 5 in nonfunctioning pituitary adenomas: a high throughput TMA, immunohistochemical study. J Clin Endocrinol Metab 97:1745–1751PubMedCrossRef Ramirez C, Cheng S, Vargas G et al (2012) Expression of Ki-67, PTTG1, FGFR4, and SSTR 2, 3, and 5 in nonfunctioning pituitary adenomas: a high throughput TMA, immunohistochemical study. J Clin Endocrinol Metab 97:1745–1751PubMedCrossRef
11.
go back to reference Acosta-Gomez MJ, Muros MA, Llamas-Elvira JM et al (2005) The role of somatostatin receptor scintigraphy in patients with pituitary adenoma or post-surgical recurrent tumours. Br J Radiol 78:110–115PubMedCrossRef Acosta-Gomez MJ, Muros MA, Llamas-Elvira JM et al (2005) The role of somatostatin receptor scintigraphy in patients with pituitary adenoma or post-surgical recurrent tumours. Br J Radiol 78:110–115PubMedCrossRef
12.
go back to reference Jaquet P, Ouafik L, Saveanu A et al (1999) Quantitative and functional expression of somatostatin receptor subtypes in human prolactinomas. J Clin Endocrinol Metab 84:3268–3276PubMed Jaquet P, Ouafik L, Saveanu A et al (1999) Quantitative and functional expression of somatostatin receptor subtypes in human prolactinomas. J Clin Endocrinol Metab 84:3268–3276PubMed
13.
go back to reference Taboada GF, Luque RM, Bastos W et al (2007) Quantitative analysis of somatostatin receptor subtype (SSTR1-5) gene expression levels in somatotropinomas and non-functioning pituitary adenomas. Eur J Endocrinol 156:65–74PubMedCrossRef Taboada GF, Luque RM, Bastos W et al (2007) Quantitative analysis of somatostatin receptor subtype (SSTR1-5) gene expression levels in somatotropinomas and non-functioning pituitary adenomas. Eur J Endocrinol 156:65–74PubMedCrossRef
14.
go back to reference Saveanu A, Gunz G, Guillen S et al (2006) Somatostatin and dopamine-somatostatin multiple ligands directed towards somatostatin and dopamine receptors in pituitary adenomas. Neuroendocrinology 83:258–263PubMedCrossRef Saveanu A, Gunz G, Guillen S et al (2006) Somatostatin and dopamine-somatostatin multiple ligands directed towards somatostatin and dopamine receptors in pituitary adenomas. Neuroendocrinology 83:258–263PubMedCrossRef
15.
go back to reference Hofland LJ, Lamberts SW, Feelders RA (2010) Role of somatostatin receptors in normal and tumoral pituitary corticotropic cells. Neuroendocrinology 92(Suppl 1):11–16PubMedCrossRef Hofland LJ, Lamberts SW, Feelders RA (2010) Role of somatostatin receptors in normal and tumoral pituitary corticotropic cells. Neuroendocrinology 92(Suppl 1):11–16PubMedCrossRef
16.
go back to reference Hofland LJ, Feelders RA, de Herder WW et al (2010) Pituitary tumours: the sst/D2 receptors as molecular targets. Mol Cell Endocrinol 326:89–98PubMedCrossRef Hofland LJ, Feelders RA, de Herder WW et al (2010) Pituitary tumours: the sst/D2 receptors as molecular targets. Mol Cell Endocrinol 326:89–98PubMedCrossRef
17.
go back to reference Fusco A, Giampietro A, Bianchi A et al (2012) Treatment with octreotide LAR in clinically non-functioning pituitary adenoma: results from a case-control study. Pituitary 15:571–578PubMedCrossRef Fusco A, Giampietro A, Bianchi A et al (2012) Treatment with octreotide LAR in clinically non-functioning pituitary adenoma: results from a case-control study. Pituitary 15:571–578PubMedCrossRef
18.
go back to reference Rahmim A, Zaidi H (2008) PET versus SPECT: strengths, limitations and challenges. Nucl Med Commun 29:193–207PubMedCrossRef Rahmim A, Zaidi H (2008) PET versus SPECT: strengths, limitations and challenges. Nucl Med Commun 29:193–207PubMedCrossRef
19.
go back to reference Kuyumcu S, Ozkan ZG, Sanli Y et al (2013) Physiological and tumoral uptake of (68)Ga-DOTATATE: standardized uptake values and challenges in interpretation. Ann Nucl Med 27:538–545PubMedCrossRef Kuyumcu S, Ozkan ZG, Sanli Y et al (2013) Physiological and tumoral uptake of (68)Ga-DOTATATE: standardized uptake values and challenges in interpretation. Ann Nucl Med 27:538–545PubMedCrossRef
20.
go back to reference Kunikowska J, Krolicki L, Pawlak D et al (2012) Semiquantitative analysis and characterization of physiological biodistribution of (68)Ga-DOTA-TATE PET/CT. Clin Nucl Med 37:1052–1057PubMedCrossRef Kunikowska J, Krolicki L, Pawlak D et al (2012) Semiquantitative analysis and characterization of physiological biodistribution of (68)Ga-DOTA-TATE PET/CT. Clin Nucl Med 37:1052–1057PubMedCrossRef
21.
go back to reference Boy C, Heusner TA, Poeppel TD et al (2011) 68 Ga-DOTATOC PET/CT and somatostatin receptor (sst1–sst5) expression in normal human tissue: correlation of sst2 mRNA and SUVmax. Eur J Nucl Med Mol Imaging 38:1224–1236PubMedCrossRef Boy C, Heusner TA, Poeppel TD et al (2011) 68 Ga-DOTATOC PET/CT and somatostatin receptor (sst1–sst5) expression in normal human tissue: correlation of sst2 mRNA and SUVmax. Eur J Nucl Med Mol Imaging 38:1224–1236PubMedCrossRef
22.
go back to reference Shastry M, Kayani I, Wild D et al (2010) Distribution pattern of 68 Ga-DOTATATE in disease-free patients. Nucl Med Commun 31:1025–1032PubMed Shastry M, Kayani I, Wild D et al (2010) Distribution pattern of 68 Ga-DOTATATE in disease-free patients. Nucl Med Commun 31:1025–1032PubMed
23.
go back to reference Veit JA, Boehm B, Luster M et al (2013) Detection of paranasal ectopic adrenocorticotropic hormone-secreting pituitary adenoma by Ga-68-DOTANOC positron-emission tomography-computed tomography. Laryngoscope 123:1132–1135PubMedCrossRef Veit JA, Boehm B, Luster M et al (2013) Detection of paranasal ectopic adrenocorticotropic hormone-secreting pituitary adenoma by Ga-68-DOTANOC positron-emission tomography-computed tomography. Laryngoscope 123:1132–1135PubMedCrossRef
24.
go back to reference Kwekkeboom DJ, de Herder WW, Kam BL et al (2008) Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0, Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 26:2124–2130PubMedCrossRef Kwekkeboom DJ, de Herder WW, Kam BL et al (2008) Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0, Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 26:2124–2130PubMedCrossRef
25.
go back to reference van Essen M, Krenning EP, Kooij PP et al (2006) Effects of therapy with [177Lu-DOTA0, Tyr3]octreotate in patients with paraganglioma, meningioma, small cell lung carcinoma, and melanoma. J Nucl Med 47:1599–1606PubMed van Essen M, Krenning EP, Kooij PP et al (2006) Effects of therapy with [177Lu-DOTA0, Tyr3]octreotate in patients with paraganglioma, meningioma, small cell lung carcinoma, and melanoma. J Nucl Med 47:1599–1606PubMed
26.
go back to reference Bartolomei M, Bodei L, De Cicco C et al (2009) Peptide receptor radionuclide therapy with (90)Y-DOTATOC in recurrent meningioma. Eur J Nucl Med Mol Imaging 36:1407–1416PubMedCrossRef Bartolomei M, Bodei L, De Cicco C et al (2009) Peptide receptor radionuclide therapy with (90)Y-DOTATOC in recurrent meningioma. Eur J Nucl Med Mol Imaging 36:1407–1416PubMedCrossRef
27.
go back to reference Baldari S, Ferrau F, Alafaci C et al (2012) First demonstration of the effectiveness of peptide receptor radionuclide therapy (PRRT) with 111In-DTPA-octreotide in a giant PRL-secreting pituitary adenoma resistant to conventional treatment. Pituitary 15(Suppl 1):S57–S60PubMedCrossRef Baldari S, Ferrau F, Alafaci C et al (2012) First demonstration of the effectiveness of peptide receptor radionuclide therapy (PRRT) with 111In-DTPA-octreotide in a giant PRL-secreting pituitary adenoma resistant to conventional treatment. Pituitary 15(Suppl 1):S57–S60PubMedCrossRef
28.
29.
go back to reference Siegel JA, Thomas SR, Stubbs JB et al (1999) MIRD pamphlet no. 16: techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates. J Nucl Med 40(2):37S–61SPubMed Siegel JA, Thomas SR, Stubbs JB et al (1999) MIRD pamphlet no. 16: techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates. J Nucl Med 40(2):37S–61SPubMed
30.
go back to reference Pernicone PJ, Scheithauer BW, Sebo TJ et al (1997) Pituitary carcinoma: a clinicopathologic study of 15 cases. Cancer 79:804–812PubMedCrossRef Pernicone PJ, Scheithauer BW, Sebo TJ et al (1997) Pituitary carcinoma: a clinicopathologic study of 15 cases. Cancer 79:804–812PubMedCrossRef
31.
go back to reference Salehi F, Agur A, Scheithauer BW et al (2009) Ki-67 in pituitary neoplasms: a review–part I. Neurosurgery 65:429–437 discussion 437PubMedCrossRef Salehi F, Agur A, Scheithauer BW et al (2009) Ki-67 in pituitary neoplasms: a review–part I. Neurosurgery 65:429–437 discussion 437PubMedCrossRef
32.
go back to reference Janssen MH, Ollers MC, van Stiphout RG et al (2012) PET-based treatment response evaluation in rectal cancer: prediction and validation. Int J Radiat Oncol Biol Phys 82:871–876PubMedCrossRef Janssen MH, Ollers MC, van Stiphout RG et al (2012) PET-based treatment response evaluation in rectal cancer: prediction and validation. Int J Radiat Oncol Biol Phys 82:871–876PubMedCrossRef
33.
go back to reference van Elmpt W, Ollers M, Dingemans AM et al (2012) Response assessment using 18F-FDG PET early in the course of radiotherapy correlates with survival in advanced-stage non-small cell lung cancer. J Nucl Med 53:1514–1520PubMedCrossRef van Elmpt W, Ollers M, Dingemans AM et al (2012) Response assessment using 18F-FDG PET early in the course of radiotherapy correlates with survival in advanced-stage non-small cell lung cancer. J Nucl Med 53:1514–1520PubMedCrossRef
34.
go back to reference Haug AR, Auernhammer CJ, Wangler B et al (2010) 68 Ga-DOTATATE PET/CT for the early prediction of response to somatostatin receptor-mediated radionuclide therapy in patients with well-differentiated neuroendocrine tumors. J Nucl Med 51:1349–1356PubMedCrossRef Haug AR, Auernhammer CJ, Wangler B et al (2010) 68 Ga-DOTATATE PET/CT for the early prediction of response to somatostatin receptor-mediated radionuclide therapy in patients with well-differentiated neuroendocrine tumors. J Nucl Med 51:1349–1356PubMedCrossRef
35.
go back to reference Kwekkeboom DJ, Teunissen JJ, Bakker WH et al (2005) Radiolabeled somatostatin analog [177Lu-DOTA0, Tyr3]octreotate in patients with endocrine gastroenteropancreatic tumors. J Clin Oncol 23:2754–2762PubMedCrossRef Kwekkeboom DJ, Teunissen JJ, Bakker WH et al (2005) Radiolabeled somatostatin analog [177Lu-DOTA0, Tyr3]octreotate in patients with endocrine gastroenteropancreatic tumors. J Clin Oncol 23:2754–2762PubMedCrossRef
36.
go back to reference Hanscheid H, Sweeney RA, Flentje M et al (2012) PET SUV correlates with radionuclide uptake in peptide receptor therapy in meningioma. Eur J Nucl Med Mol Imaging 39:1284–1288PubMedCrossRef Hanscheid H, Sweeney RA, Flentje M et al (2012) PET SUV correlates with radionuclide uptake in peptide receptor therapy in meningioma. Eur J Nucl Med Mol Imaging 39:1284–1288PubMedCrossRef
37.
go back to reference Cremonesi M, Botta F, Di Dia A et al (2010) Dosimetry for treatment with radiolabelled somatostatin analogues. A review. Q J Nucl Med Mol Imaging 54:37–51PubMed Cremonesi M, Botta F, Di Dia A et al (2010) Dosimetry for treatment with radiolabelled somatostatin analogues. A review. Q J Nucl Med Mol Imaging 54:37–51PubMed
38.
go back to reference Hindorf C, Chittenden S, Causer L et al (2007) Dosimetry for (90)Y-DOTATOC therapies in patients with neuroendocrine tumors. Cancer Biother Radiopharm 22:130–135PubMedCrossRef Hindorf C, Chittenden S, Causer L et al (2007) Dosimetry for (90)Y-DOTATOC therapies in patients with neuroendocrine tumors. Cancer Biother Radiopharm 22:130–135PubMedCrossRef
39.
go back to reference Kaltsas GA, Papadogias D, Makras P et al (2005) Treatment of advanced neuroendocrine tumours with radiolabelled somatostatin analogues. Endocr Relat Cancer 12:683–699PubMedCrossRef Kaltsas GA, Papadogias D, Makras P et al (2005) Treatment of advanced neuroendocrine tumours with radiolabelled somatostatin analogues. Endocr Relat Cancer 12:683–699PubMedCrossRef
40.
go back to reference Villard L, Romer A, Marincek N et al (2012) Cohort study of somatostatin-based radiopeptide therapy with [(90)Y-DOTA]-TOC versus [(90)Y-DOTA]-TOC plus [(177)Lu-DOTA]-TOC in neuroendocrine cancers. J Clin Oncol 30:1100–1106PubMedCrossRef Villard L, Romer A, Marincek N et al (2012) Cohort study of somatostatin-based radiopeptide therapy with [(90)Y-DOTA]-TOC versus [(90)Y-DOTA]-TOC plus [(177)Lu-DOTA]-TOC in neuroendocrine cancers. J Clin Oncol 30:1100–1106PubMedCrossRef
Metadata
Title
Peptide receptor radionuclide therapy for aggressive atypical pituitary adenoma/carcinoma: variable clinical response in preliminary evaluation
Authors
Jillian Maclean
Matthew Aldridge
Jamshed Bomanji
Susan Short
Naomi Fersht
Publication date
01-12-2014
Publisher
Springer US
Published in
Pituitary / Issue 6/2014
Print ISSN: 1386-341X
Electronic ISSN: 1573-7403
DOI
https://doi.org/10.1007/s11102-013-0540-y

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