89Zr-Trastuzumab PET/CT Imaging of HER2-Positive Breast Cancer for Predicting Pathological Complete Response after Neoadjuvant Systemic Therapy: A Feasibility Study

D. G.J. Linders; M. M. Deken; M. A. van Dam; M. N.J.M. Wasser; E. M.C. Voormolen; J. R. Kroep; G. A.M.S. van Dongen; D. Vugts; H. M. Oosterkamp; M. E. Straver; C. J.H. van de Velde; D. Cohen; P. Dibbets-Schneider; F. H.P. van Velden; L. M. Pereira Arias-Bouda; A. L. Vahrmeijer; G. J. Liefers; L. F. de Geus-Oei; D. E. Hilling

doi:10.3390/cancers15204980

⁸⁹Zr-Trastuzumab PET/CT Imaging of HER2-Positive Breast Cancer for Predicting Pathological Complete Response after Neoadjuvant Systemic Therapy: A Feasibility Study

D. G.J. Linders^*, M. M. Deken, M. A. van Dam, M. N.J.M. Wasser, E. M.C. Voormolen, J. R. Kroep, G. A.M.S. van Dongen, D. Vugts, H. M. Oosterkamp, M. E. Straver, C. J.H. van de Velde, D. Cohen, P. Dibbets-Schneider, F. H.P. van Velden, L. M. Pereira Arias-Bouda, A. L. Vahrmeijer, G. J. Liefers, L. F. de Geus-Oei, D. E. Hilling^*

^*Corresponding author for this work

Surgery

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Abstract

Background:

Approximately 20% of invasive ductal breast malignancies are human epidermal growth factor receptor 2 (HER2)-positive. These patients receive neoadjuvant systemic therapy (NAT) including HER2-targeting therapies. Up to 65% of patients achieve a pathological complete response (pCR). These patients might not have needed surgery. However, accurate preoperative identification of a pCR remains challenging. A radiologic complete response (rCR) on MRI corresponds to a pCR in only 73% of patients. The current feasibility study investigates if HER2-targeted PET/CT-imaging using Zirconium-89 (⁸⁹Zr)-radiolabeled trastuzumab can be used for more accurate NAT response evaluation.

Methods:

HER2-positive breast cancer patients scheduled to undergo NAT and subsequent surgery received a ⁸⁹Zr-trastuzumab PET/CT both before (PET/CT-1) and after (PET/CT-2) NAT. Qualitative and quantitative response evaluation was performed.

Results:

Six patients were enrolled. All primary tumors could be identified on PET/CT-1. Four patients had a pCR and two a pathological partial response (pPR) in the primary tumor. Qualitative assessment of PET/CT resulted in an accuracy of 66.7%, compared to 83.3% of the standard-of-care MRI. Quantitative assessment showed a difference between the SUV_R on PET/CT-1 and PET/CT-2 (ΔSUV_R) in patients with a pPR and pCR of −48% and −90% (p = 0.133), respectively. The difference in tumor-to-blood ratio on PET/CT-1 and PET/CT-2 (ΔTBR) in patients with pPR and pCR was −79% and −94% (p = 0.133), respectively. Three patients had metastatic lymph nodes at diagnosis that were all identified on PET/CT-1. All three patients achieved a nodal pCR. Qualitative assessment of the lymph nodes with PET/CT resulted in an accuracy of 66.7%, compared to 50% of the MRI.

Conclusions:

NAT response evaluation using ⁸⁹Zr-trastuzumab PET/CT is feasible. In the current study, qualitative assessment of the PET/CT images is not superior to standard-of-care MRI. Our results suggest that quantitative assessment of ⁸⁹Zr-trastuzumab PET/CT has potential for a more accurate response evaluation of the primary tumor after NAT in HER2-positive breast cancer.

Original language	English
Article number	4980
Number of pages	16
Journal	Cancers
Volume	15
Issue number	20
DOIs	https://doi.org/10.3390/cancers15204980
Publication status	Published - 13 Oct 2023

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Publisher Copyright:
© 2023 by the authors.

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Linders, D. G. J., Deken, M. M., van Dam, M. A., Wasser, M. N. J. M., Voormolen, E. M. C., Kroep, J. R., van Dongen, G. A. M. S., Vugts, D., Oosterkamp, H. M., Straver, M. E., van de Velde, C. J. H., Cohen, D., Dibbets-Schneider, P., van Velden, F. H. P., Pereira Arias-Bouda, L. M., Vahrmeijer, A. L., Liefers, G. J., de Geus-Oei, L. F., & Hilling, D. E. (2023). ⁸⁹Zr-Trastuzumab PET/CT Imaging of HER2-Positive Breast Cancer for Predicting Pathological Complete Response after Neoadjuvant Systemic Therapy: A Feasibility Study. Cancers, 15(20), Article 4980. https://doi.org/10.3390/cancers15204980

@article{19e19f0583eb446ba967aa649c329b9e,

title = "89Zr-Trastuzumab PET/CT Imaging of HER2-Positive Breast Cancer for Predicting Pathological Complete Response after Neoadjuvant Systemic Therapy: A Feasibility Study",

abstract = "Background: Approximately 20% of invasive ductal breast malignancies are human epidermal growth factor receptor 2 (HER2)-positive. These patients receive neoadjuvant systemic therapy (NAT) including HER2-targeting therapies. Up to 65% of patients achieve a pathological complete response (pCR). These patients might not have needed surgery. However, accurate preoperative identification of a pCR remains challenging. A radiologic complete response (rCR) on MRI corresponds to a pCR in only 73% of patients. The current feasibility study investigates if HER2-targeted PET/CT-imaging using Zirconium-89 (89Zr)-radiolabeled trastuzumab can be used for more accurate NAT response evaluation. Methods: HER2-positive breast cancer patients scheduled to undergo NAT and subsequent surgery received a 89Zr-trastuzumab PET/CT both before (PET/CT-1) and after (PET/CT-2) NAT. Qualitative and quantitative response evaluation was performed. Results: Six patients were enrolled. All primary tumors could be identified on PET/CT-1. Four patients had a pCR and two a pathological partial response (pPR) in the primary tumor. Qualitative assessment of PET/CT resulted in an accuracy of 66.7%, compared to 83.3% of the standard-of-care MRI. Quantitative assessment showed a difference between the SUVR on PET/CT-1 and PET/CT-2 (ΔSUVR) in patients with a pPR and pCR of −48% and −90% (p = 0.133), respectively. The difference in tumor-to-blood ratio on PET/CT-1 and PET/CT-2 (ΔTBR) in patients with pPR and pCR was −79% and −94% (p = 0.133), respectively. Three patients had metastatic lymph nodes at diagnosis that were all identified on PET/CT-1. All three patients achieved a nodal pCR. Qualitative assessment of the lymph nodes with PET/CT resulted in an accuracy of 66.7%, compared to 50% of the MRI. Conclusions: NAT response evaluation using 89Zr-trastuzumab PET/CT is feasible. In the current study, qualitative assessment of the PET/CT images is not superior to standard-of-care MRI. Our results suggest that quantitative assessment of 89Zr-trastuzumab PET/CT has potential for a more accurate response evaluation of the primary tumor after NAT in HER2-positive breast cancer.",

author = "Linders, {D. G.J.} and Deken, {M. M.} and {van Dam}, {M. A.} and Wasser, {M. N.J.M.} and Voormolen, {E. M.C.} and Kroep, {J. R.} and {van Dongen}, {G. A.M.S.} and D. Vugts and Oosterkamp, {H. M.} and Straver, {M. E.} and {van de Velde}, {C. J.H.} and D. Cohen and P. Dibbets-Schneider and {van Velden}, {F. H.P.} and {Pereira Arias-Bouda}, {L. M.} and Vahrmeijer, {A. L.} and Liefers, {G. J.} and {de Geus-Oei}, {L. F.} and Hilling, {D. E.}",

note = "Publisher Copyright: {\textcopyright} 2023 by the authors.",

year = "2023",

month = oct,

day = "13",

doi = "10.3390/cancers15204980",

language = "English",

volume = "15",

journal = "Cancers",

issn = "2072-6694",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "20",

}

Linders, DGJ, Deken, MM, van Dam, MA, Wasser, MNJM, Voormolen, EMC, Kroep, JR, van Dongen, GAMS, Vugts, D, Oosterkamp, HM, Straver, ME, van de Velde, CJH, Cohen, D, Dibbets-Schneider, P, van Velden, FHP, Pereira Arias-Bouda, LM, Vahrmeijer, AL, Liefers, GJ, de Geus-Oei, LF & Hilling, DE 2023, '⁸⁹Zr-Trastuzumab PET/CT Imaging of HER2-Positive Breast Cancer for Predicting Pathological Complete Response after Neoadjuvant Systemic Therapy: A Feasibility Study', Cancers, vol. 15, no. 20, 4980. https://doi.org/10.3390/cancers15204980

TY - JOUR

T1 - 89Zr-Trastuzumab PET/CT Imaging of HER2-Positive Breast Cancer for Predicting Pathological Complete Response after Neoadjuvant Systemic Therapy

T2 - A Feasibility Study

AU - Linders, D. G.J.

AU - Deken, M. M.

AU - van Dam, M. A.

AU - Wasser, M. N.J.M.

AU - Voormolen, E. M.C.

AU - Kroep, J. R.

AU - van Dongen, G. A.M.S.

AU - Vugts, D.

AU - Oosterkamp, H. M.

AU - Straver, M. E.

AU - van de Velde, C. J.H.

AU - Cohen, D.

AU - Dibbets-Schneider, P.

AU - van Velden, F. H.P.

AU - Pereira Arias-Bouda, L. M.

AU - Vahrmeijer, A. L.

AU - Liefers, G. J.

AU - de Geus-Oei, L. F.

AU - Hilling, D. E.

PY - 2023/10/13

Y1 - 2023/10/13

N2 - Background: Approximately 20% of invasive ductal breast malignancies are human epidermal growth factor receptor 2 (HER2)-positive. These patients receive neoadjuvant systemic therapy (NAT) including HER2-targeting therapies. Up to 65% of patients achieve a pathological complete response (pCR). These patients might not have needed surgery. However, accurate preoperative identification of a pCR remains challenging. A radiologic complete response (rCR) on MRI corresponds to a pCR in only 73% of patients. The current feasibility study investigates if HER2-targeted PET/CT-imaging using Zirconium-89 (89Zr)-radiolabeled trastuzumab can be used for more accurate NAT response evaluation. Methods: HER2-positive breast cancer patients scheduled to undergo NAT and subsequent surgery received a 89Zr-trastuzumab PET/CT both before (PET/CT-1) and after (PET/CT-2) NAT. Qualitative and quantitative response evaluation was performed. Results: Six patients were enrolled. All primary tumors could be identified on PET/CT-1. Four patients had a pCR and two a pathological partial response (pPR) in the primary tumor. Qualitative assessment of PET/CT resulted in an accuracy of 66.7%, compared to 83.3% of the standard-of-care MRI. Quantitative assessment showed a difference between the SUVR on PET/CT-1 and PET/CT-2 (ΔSUVR) in patients with a pPR and pCR of −48% and −90% (p = 0.133), respectively. The difference in tumor-to-blood ratio on PET/CT-1 and PET/CT-2 (ΔTBR) in patients with pPR and pCR was −79% and −94% (p = 0.133), respectively. Three patients had metastatic lymph nodes at diagnosis that were all identified on PET/CT-1. All three patients achieved a nodal pCR. Qualitative assessment of the lymph nodes with PET/CT resulted in an accuracy of 66.7%, compared to 50% of the MRI. Conclusions: NAT response evaluation using 89Zr-trastuzumab PET/CT is feasible. In the current study, qualitative assessment of the PET/CT images is not superior to standard-of-care MRI. Our results suggest that quantitative assessment of 89Zr-trastuzumab PET/CT has potential for a more accurate response evaluation of the primary tumor after NAT in HER2-positive breast cancer.

AB - Background: Approximately 20% of invasive ductal breast malignancies are human epidermal growth factor receptor 2 (HER2)-positive. These patients receive neoadjuvant systemic therapy (NAT) including HER2-targeting therapies. Up to 65% of patients achieve a pathological complete response (pCR). These patients might not have needed surgery. However, accurate preoperative identification of a pCR remains challenging. A radiologic complete response (rCR) on MRI corresponds to a pCR in only 73% of patients. The current feasibility study investigates if HER2-targeted PET/CT-imaging using Zirconium-89 (89Zr)-radiolabeled trastuzumab can be used for more accurate NAT response evaluation. Methods: HER2-positive breast cancer patients scheduled to undergo NAT and subsequent surgery received a 89Zr-trastuzumab PET/CT both before (PET/CT-1) and after (PET/CT-2) NAT. Qualitative and quantitative response evaluation was performed. Results: Six patients were enrolled. All primary tumors could be identified on PET/CT-1. Four patients had a pCR and two a pathological partial response (pPR) in the primary tumor. Qualitative assessment of PET/CT resulted in an accuracy of 66.7%, compared to 83.3% of the standard-of-care MRI. Quantitative assessment showed a difference between the SUVR on PET/CT-1 and PET/CT-2 (ΔSUVR) in patients with a pPR and pCR of −48% and −90% (p = 0.133), respectively. The difference in tumor-to-blood ratio on PET/CT-1 and PET/CT-2 (ΔTBR) in patients with pPR and pCR was −79% and −94% (p = 0.133), respectively. Three patients had metastatic lymph nodes at diagnosis that were all identified on PET/CT-1. All three patients achieved a nodal pCR. Qualitative assessment of the lymph nodes with PET/CT resulted in an accuracy of 66.7%, compared to 50% of the MRI. Conclusions: NAT response evaluation using 89Zr-trastuzumab PET/CT is feasible. In the current study, qualitative assessment of the PET/CT images is not superior to standard-of-care MRI. Our results suggest that quantitative assessment of 89Zr-trastuzumab PET/CT has potential for a more accurate response evaluation of the primary tumor after NAT in HER2-positive breast cancer.

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U2 - 10.3390/cancers15204980

DO - 10.3390/cancers15204980

M3 - Article

C2 - 37894346

AN - SCOPUS:85175013121

SN - 2072-6694

VL - 15

JO - Cancers

JF - Cancers

IS - 20

M1 - 4980

ER -