Fluorescence detection of pituitary neuroendocrine tumour during endoscopic transsphenoidal surgery using bevacizumab-800CW: a non-randomised, non-blinded, single centre feasibility and dose finding trial [DEPARTURE trial]

I Schmidt; R A Vergeer; M R Postma; G van den Berg; A J Sterkenburg; A G W Korsten-Meijer; R A Feijen; S Kruijff; A P van Beek; W F A den Dunnen; D J Robinson; J M C van Dijk; W B Nagengast; J M A Kuijlen

doi:10.1007/s00259-024-06947-9

Fluorescence detection of pituitary neuroendocrine tumour during endoscopic transsphenoidal surgery using bevacizumab-800CW: a non-randomised, non-blinded, single centre feasibility and dose finding trial [DEPARTURE trial]

I Schmidt, R A Vergeer, M R Postma, G van den Berg, A J Sterkenburg, A G W Korsten-Meijer, R A Feijen, S Kruijff, A P van Beek, W F A den Dunnen, D J Robinson, J M C van Dijk, W B Nagengast, J M A Kuijlen

Nutrition Research in Medicine (NiM)

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PURPOSE: Achieving endocrine remission by gross total resection is challenging in pituitary neuroendocrine tumours (PitNETs) with cavernous sinus invasion. This study aims to assess the safety, feasibility, and optimal dose for intraoperative fluorescence imaging as an added instrument to discriminate PitNET from surrounding tissue using bevacizumab-800CW, targeting vascular endothelial growth factor A (VEGF-A).

METHODS: In part I, dose-escalation (0-4∙5-10-25 mg) was performed in 4 groups of 3 patients with PitNETs Knosp grade 3-4. In part II, after interim analysis, the 10 mg and 25 mg groups were expanded to a total of 6 patients. Quantitative fluoroscence molecular endoscopy consisted of wide field fluorescence molecular endoscopy and multi-diameter single fiber reflectance / single fiber fluorescence spectroscopy. Mean fluorescence intensity (MFI) of the fresh surgical specimen was calculated and VEGF-staining was performed.

RESULTS: Eighteen patients were included. All doses were well tolerated. Three serious adverse events were registered, but none were tracer-related. Part I showed an adequate in-vivo tumour-to-background ratio for both 10 mg (TBR 2∙00 [1∙86, 2∙19]) and 25 mg (TBR 2∙10, [1∙86, 2∙58]). Part II revealed a substantially higher MFI in the 25 mg group. With both 10 mg and 25 mg a statistically significant difference between tumour and surrounding tissue was detected (p < 0∙0001). All surgical specimens had VEGF-A expression.

CONCLUSION: This study demonstrates the safety and feasibility of quantitative fluorescence molecular endoscopy during PitNET surgery. Both 10 mg and 25 mg bevacizumab-800CW result in clear differentiation in-vivo, with improved contrast ex-vivo (MFI) in the 25 mg group.

TRIAL REGISTRATION: NCT04212793 / Study Details| Detection of PitNET Tissue During TSS Using Bevacizumab800CW| ClinicalTrials.gov.

Originele taal-2	English
Aantal pagina's	9
Tijdschrift	European Journal of Nuclear Medicine and Molecular Imaging
DOI's	https://doi.org/10.1007/s00259-024-06947-9
Status	E-pub ahead of print - 11-okt.-2024

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Schmidt, I., Vergeer, R. A., Postma, M. R., Berg, G. V. D., Sterkenburg, A. J., Korsten-Meijer, A. G. W., Feijen, R. A., Kruijff, S., Beek, A. P. V., Dunnen, W. F. A. D., Robinson, D. J., Dijk, J. M. C. V., Nagengast, W. B., & Kuijlen, J. M. A. (2024). Fluorescence detection of pituitary neuroendocrine tumour during endoscopic transsphenoidal surgery using bevacizumab-800CW: a non-randomised, non-blinded, single centre feasibility and dose finding trial [DEPARTURE trial]. European Journal of Nuclear Medicine and Molecular Imaging. Online publicatie vooraf. https://doi.org/10.1007/s00259-024-06947-9

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title = "Fluorescence detection of pituitary neuroendocrine tumour during endoscopic transsphenoidal surgery using bevacizumab-800CW: a non-randomised, non-blinded, single centre feasibility and dose finding trial [DEPARTURE trial]",

abstract = "PURPOSE: Achieving endocrine remission by gross total resection is challenging in pituitary neuroendocrine tumours (PitNETs) with cavernous sinus invasion. This study aims to assess the safety, feasibility, and optimal dose for intraoperative fluorescence imaging as an added instrument to discriminate PitNET from surrounding tissue using bevacizumab-800CW, targeting vascular endothelial growth factor A (VEGF-A).METHODS: In part I, dose-escalation (0-4∙5-10-25 mg) was performed in 4 groups of 3 patients with PitNETs Knosp grade 3-4. In part II, after interim analysis, the 10 mg and 25 mg groups were expanded to a total of 6 patients. Quantitative fluoroscence molecular endoscopy consisted of wide field fluorescence molecular endoscopy and multi-diameter single fiber reflectance / single fiber fluorescence spectroscopy. Mean fluorescence intensity (MFI) of the fresh surgical specimen was calculated and VEGF-staining was performed.RESULTS: Eighteen patients were included. All doses were well tolerated. Three serious adverse events were registered, but none were tracer-related. Part I showed an adequate in-vivo tumour-to-background ratio for both 10 mg (TBR 2∙00 [1∙86, 2∙19]) and 25 mg (TBR 2∙10, [1∙86, 2∙58]). Part II revealed a substantially higher MFI in the 25 mg group. With both 10 mg and 25 mg a statistically significant difference between tumour and surrounding tissue was detected (p < 0∙0001). All surgical specimens had VEGF-A expression.CONCLUSION: This study demonstrates the safety and feasibility of quantitative fluorescence molecular endoscopy during PitNET surgery. Both 10 mg and 25 mg bevacizumab-800CW result in clear differentiation in-vivo, with improved contrast ex-vivo (MFI) in the 25 mg group.TRIAL REGISTRATION: NCT04212793 / Study Details| Detection of PitNET Tissue During TSS Using Bevacizumab800CW| ClinicalTrials.gov.",

author = "I Schmidt and Vergeer, {R A} and Postma, {M R} and Berg, {G van den} and Sterkenburg, {A J} and Korsten-Meijer, {A G W} and Feijen, {R A} and S Kruijff and Beek, {A P van} and Dunnen, {W F A den} and Robinson, {D J} and Dijk, {J M C van} and Nagengast, {W B} and Kuijlen, {J M A}",

note = "{\textcopyright} 2024. The Author(s).",

year = "2024",

month = oct,

day = "11",

doi = "10.1007/s00259-024-06947-9",

language = "English",

journal = "European Journal of Nuclear Medicine and Molecular Imaging",

issn = "1619-7070",

publisher = "Springer",

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Schmidt, I, Vergeer, RA , Postma, MR, Berg, GVD, Sterkenburg, AJ , Korsten-Meijer, AGW, Feijen, RA, Kruijff, S , Beek, APV , Dunnen, WFAD, Robinson, DJ, Dijk, JMCV , Nagengast, WB & Kuijlen, JMA 2024, 'Fluorescence detection of pituitary neuroendocrine tumour during endoscopic transsphenoidal surgery using bevacizumab-800CW: a non-randomised, non-blinded, single centre feasibility and dose finding trial [DEPARTURE trial]', European Journal of Nuclear Medicine and Molecular Imaging. https://doi.org/10.1007/s00259-024-06947-9

Fluorescence detection of pituitary neuroendocrine tumour during endoscopic transsphenoidal surgery using bevacizumab-800CW: a non-randomised, non-blinded, single centre feasibility and dose finding trial [DEPARTURE trial]. / Schmidt, I; Vergeer, R A ; Postma, M R et al.
In: European Journal of Nuclear Medicine and Molecular Imaging, 11.10.2024.

Onderzoeksoutput › Academic › peer review

TY - JOUR

T1 - Fluorescence detection of pituitary neuroendocrine tumour during endoscopic transsphenoidal surgery using bevacizumab-800CW

T2 - a non-randomised, non-blinded, single centre feasibility and dose finding trial [DEPARTURE trial]

AU - Schmidt, I

AU - Vergeer, R A

AU - Postma, M R

AU - Berg, G van den

AU - Sterkenburg, A J

AU - Korsten-Meijer, A G W

AU - Feijen, R A

AU - Kruijff, S

AU - Beek, A P van

AU - Dunnen, W F A den

AU - Robinson, D J

AU - Dijk, J M C van

AU - Nagengast, W B

AU - Kuijlen, J M A

PY - 2024/10/11

Y1 - 2024/10/11

N2 - PURPOSE: Achieving endocrine remission by gross total resection is challenging in pituitary neuroendocrine tumours (PitNETs) with cavernous sinus invasion. This study aims to assess the safety, feasibility, and optimal dose for intraoperative fluorescence imaging as an added instrument to discriminate PitNET from surrounding tissue using bevacizumab-800CW, targeting vascular endothelial growth factor A (VEGF-A).METHODS: In part I, dose-escalation (0-4∙5-10-25 mg) was performed in 4 groups of 3 patients with PitNETs Knosp grade 3-4. In part II, after interim analysis, the 10 mg and 25 mg groups were expanded to a total of 6 patients. Quantitative fluoroscence molecular endoscopy consisted of wide field fluorescence molecular endoscopy and multi-diameter single fiber reflectance / single fiber fluorescence spectroscopy. Mean fluorescence intensity (MFI) of the fresh surgical specimen was calculated and VEGF-staining was performed.RESULTS: Eighteen patients were included. All doses were well tolerated. Three serious adverse events were registered, but none were tracer-related. Part I showed an adequate in-vivo tumour-to-background ratio for both 10 mg (TBR 2∙00 [1∙86, 2∙19]) and 25 mg (TBR 2∙10, [1∙86, 2∙58]). Part II revealed a substantially higher MFI in the 25 mg group. With both 10 mg and 25 mg a statistically significant difference between tumour and surrounding tissue was detected (p < 0∙0001). All surgical specimens had VEGF-A expression.CONCLUSION: This study demonstrates the safety and feasibility of quantitative fluorescence molecular endoscopy during PitNET surgery. Both 10 mg and 25 mg bevacizumab-800CW result in clear differentiation in-vivo, with improved contrast ex-vivo (MFI) in the 25 mg group.TRIAL REGISTRATION: NCT04212793 / Study Details| Detection of PitNET Tissue During TSS Using Bevacizumab800CW| ClinicalTrials.gov.

AB - PURPOSE: Achieving endocrine remission by gross total resection is challenging in pituitary neuroendocrine tumours (PitNETs) with cavernous sinus invasion. This study aims to assess the safety, feasibility, and optimal dose for intraoperative fluorescence imaging as an added instrument to discriminate PitNET from surrounding tissue using bevacizumab-800CW, targeting vascular endothelial growth factor A (VEGF-A).METHODS: In part I, dose-escalation (0-4∙5-10-25 mg) was performed in 4 groups of 3 patients with PitNETs Knosp grade 3-4. In part II, after interim analysis, the 10 mg and 25 mg groups were expanded to a total of 6 patients. Quantitative fluoroscence molecular endoscopy consisted of wide field fluorescence molecular endoscopy and multi-diameter single fiber reflectance / single fiber fluorescence spectroscopy. Mean fluorescence intensity (MFI) of the fresh surgical specimen was calculated and VEGF-staining was performed.RESULTS: Eighteen patients were included. All doses were well tolerated. Three serious adverse events were registered, but none were tracer-related. Part I showed an adequate in-vivo tumour-to-background ratio for both 10 mg (TBR 2∙00 [1∙86, 2∙19]) and 25 mg (TBR 2∙10, [1∙86, 2∙58]). Part II revealed a substantially higher MFI in the 25 mg group. With both 10 mg and 25 mg a statistically significant difference between tumour and surrounding tissue was detected (p < 0∙0001). All surgical specimens had VEGF-A expression.CONCLUSION: This study demonstrates the safety and feasibility of quantitative fluorescence molecular endoscopy during PitNET surgery. Both 10 mg and 25 mg bevacizumab-800CW result in clear differentiation in-vivo, with improved contrast ex-vivo (MFI) in the 25 mg group.TRIAL REGISTRATION: NCT04212793 / Study Details| Detection of PitNET Tissue During TSS Using Bevacizumab800CW| ClinicalTrials.gov.

U2 - 10.1007/s00259-024-06947-9

DO - 10.1007/s00259-024-06947-9

M3 - Article

C2 - 39390132

SN - 1619-7070

JO - European Journal of Nuclear Medicine and Molecular Imaging

JF - European Journal of Nuclear Medicine and Molecular Imaging

ER -

Schmidt I, Vergeer RA , Postma MR, Berg GVD, Sterkenburg AJ , Korsten-Meijer AGW et al. Fluorescence detection of pituitary neuroendocrine tumour during endoscopic transsphenoidal surgery using bevacizumab-800CW: a non-randomised, non-blinded, single centre feasibility and dose finding trial [DEPARTURE trial]. European Journal of Nuclear Medicine and Molecular Imaging. 2024 okt. 11. Epub 2024 okt. 11. doi: 10.1007/s00259-024-06947-9