Dose response modelling of secretory cell loss in salivary glands using PSMA PET

V Mohan; N M Bruin; R J H M Steenbakkers; W Noordzij; C H J Terhaard; B de Keizer; A Al-Mamgani; J B van de Kamer; J-J Sonke; W V Vogel

doi:10.1016/j.radonc.2022.10.038

Dose response modelling of secretory cell loss in salivary glands using PSMA PET

V Mohan, N M Bruin, R J H M Steenbakkers, W Noordzij, C H J Terhaard, B de Keizer, A Al-Mamgani, J B van de Kamer, J-J Sonke, W V Vogel

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Abstract

BACKGROUND AND PURPOSE: Xerostomia remains a common side effect of radiotherapy (RT) for patients with head and neck (H&N) cancer despite advancements in treatment planning and delivery. Secretory salivary gland cells express the prostate-specific membrane antigen (PSMA), and show significant uptake on PET scans using 68Ga/ 18F-PSMA-ligands. We aimed to objectively quantify the dose-response of salivary glands to RT using PSMA PET.

METHODS AND MATERIALS: 28 H&N cancer patients received RT with 70 Gy in 35 fractions over 7 weeks. PSMA PET/CT was acquired at baseline (BL), during treatment (DT) and at 1-&6-months post-treatment (PT 1M/PT 6M). Dose, BL- PT 1M- and PT 6M-SUV were extracted for every voxel inside each parotid (PG) and submandibular (SMG) gland. The PT 1M/6M data was analysed using a generalised linear mixed effects model.Patient-reported xerostomia and DT-PSMA loss was also analysed.

RESULTS: Dose had a relative effect on BL SUV. For a population average gland (BL-SUV of 10), every 1 Gy increment, decreased the PT 1M/PT 6M-SUV by 1.6%/1.6% for PGs and by 0.9%/1.8% for SMGs. TD 50 of the population curves was 26.5/31.3 Gy for PGs, and 22.9/27.8 Gy for SMGs at PT 1M /PT 6M. PSMA loss correlated well with patient-reported xerostomia at DT/PT 1M (Spearman's ρ = -0.64, -0.50).

CONCLUSION: A strong relationship was demonstrated between radiation dose and loss of secretory cells in salivary glands derived using PSMA PET/CT. The population curve could potentially be used as a dose planning objective, by maximising the predicted post-treatment SUV. BL scans could be used to further tailor this to individual patients.

Original language	English
Pages (from-to)	164-171
Number of pages	8
Journal	Radiotherapy & Oncology
Volume	177
Early online date	8 Nov 2022
DOIs	https://doi.org/10.1016/j.radonc.2022.10.038
Publication status	Published - Dec 2022

Keywords

Dose response
Head-and-neck cancer
PET
PSMA
Salivary glands
Toxicity

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@article{93b003a108ea4feba238e40da2dc67a0,

title = "Dose response modelling of secretory cell loss in salivary glands using PSMA PET",

abstract = "BACKGROUND AND PURPOSE: Xerostomia remains a common side effect of radiotherapy (RT) for patients with head and neck (H&N) cancer despite advancements in treatment planning and delivery. Secretory salivary gland cells express the prostate-specific membrane antigen (PSMA), and show significant uptake on PET scans using 68Ga/ 18F-PSMA-ligands. We aimed to objectively quantify the dose-response of salivary glands to RT using PSMA PET. METHODS AND MATERIALS: 28 H&N cancer patients received RT with 70 Gy in 35 fractions over 7 weeks. PSMA PET/CT was acquired at baseline (BL), during treatment (DT) and at 1-&6-months post-treatment (PT 1M/PT 6M). Dose, BL- PT 1M- and PT 6M-SUV were extracted for every voxel inside each parotid (PG) and submandibular (SMG) gland. The PT 1M/6M data was analysed using a generalised linear mixed effects model.Patient-reported xerostomia and DT-PSMA loss was also analysed. RESULTS: Dose had a relative effect on BL SUV. For a population average gland (BL-SUV of 10), every 1 Gy increment, decreased the PT 1M/PT 6M-SUV by 1.6%/1.6% for PGs and by 0.9%/1.8% for SMGs. TD 50 of the population curves was 26.5/31.3 Gy for PGs, and 22.9/27.8 Gy for SMGs at PT 1M /PT 6M. PSMA loss correlated well with patient-reported xerostomia at DT/PT 1M (Spearman's ρ = -0.64, -0.50). CONCLUSION: A strong relationship was demonstrated between radiation dose and loss of secretory cells in salivary glands derived using PSMA PET/CT. The population curve could potentially be used as a dose planning objective, by maximising the predicted post-treatment SUV. BL scans could be used to further tailor this to individual patients.",

keywords = "Dose response, Head-and-neck cancer, PET, PSMA, Salivary glands, Toxicity",

author = "V Mohan and Bruin, {N M} and Steenbakkers, {R J H M} and W Noordzij and Terhaard, {C H J} and {de Keizer}, B and A Al-Mamgani and {van de Kamer}, {J B} and J-J Sonke and Vogel, {W V}",

note = "Funding Information: This work was supported by the Dutch Cancer Society KWF [Research Grant: 10606/2016–2]. Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = dec,

doi = "10.1016/j.radonc.2022.10.038",

language = "English",

volume = "177",

pages = "164--171",

journal = "Radiotherapy & Oncology",

issn = "0167-8140",

publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Dose response modelling of secretory cell loss in salivary glands using PSMA PET

AU - Mohan, V

AU - Bruin, N M

AU - Steenbakkers, R J H M

AU - Noordzij, W

AU - Terhaard, C H J

AU - de Keizer, B

AU - Al-Mamgani, A

AU - van de Kamer, J B

AU - Sonke, J-J

AU - Vogel, W V

PY - 2022/12

Y1 - 2022/12

N2 - BACKGROUND AND PURPOSE: Xerostomia remains a common side effect of radiotherapy (RT) for patients with head and neck (H&N) cancer despite advancements in treatment planning and delivery. Secretory salivary gland cells express the prostate-specific membrane antigen (PSMA), and show significant uptake on PET scans using 68Ga/ 18F-PSMA-ligands. We aimed to objectively quantify the dose-response of salivary glands to RT using PSMA PET. METHODS AND MATERIALS: 28 H&N cancer patients received RT with 70 Gy in 35 fractions over 7 weeks. PSMA PET/CT was acquired at baseline (BL), during treatment (DT) and at 1-&6-months post-treatment (PT 1M/PT 6M). Dose, BL- PT 1M- and PT 6M-SUV were extracted for every voxel inside each parotid (PG) and submandibular (SMG) gland. The PT 1M/6M data was analysed using a generalised linear mixed effects model.Patient-reported xerostomia and DT-PSMA loss was also analysed. RESULTS: Dose had a relative effect on BL SUV. For a population average gland (BL-SUV of 10), every 1 Gy increment, decreased the PT 1M/PT 6M-SUV by 1.6%/1.6% for PGs and by 0.9%/1.8% for SMGs. TD 50 of the population curves was 26.5/31.3 Gy for PGs, and 22.9/27.8 Gy for SMGs at PT 1M /PT 6M. PSMA loss correlated well with patient-reported xerostomia at DT/PT 1M (Spearman's ρ = -0.64, -0.50). CONCLUSION: A strong relationship was demonstrated between radiation dose and loss of secretory cells in salivary glands derived using PSMA PET/CT. The population curve could potentially be used as a dose planning objective, by maximising the predicted post-treatment SUV. BL scans could be used to further tailor this to individual patients.

AB - BACKGROUND AND PURPOSE: Xerostomia remains a common side effect of radiotherapy (RT) for patients with head and neck (H&N) cancer despite advancements in treatment planning and delivery. Secretory salivary gland cells express the prostate-specific membrane antigen (PSMA), and show significant uptake on PET scans using 68Ga/ 18F-PSMA-ligands. We aimed to objectively quantify the dose-response of salivary glands to RT using PSMA PET. METHODS AND MATERIALS: 28 H&N cancer patients received RT with 70 Gy in 35 fractions over 7 weeks. PSMA PET/CT was acquired at baseline (BL), during treatment (DT) and at 1-&6-months post-treatment (PT 1M/PT 6M). Dose, BL- PT 1M- and PT 6M-SUV were extracted for every voxel inside each parotid (PG) and submandibular (SMG) gland. The PT 1M/6M data was analysed using a generalised linear mixed effects model.Patient-reported xerostomia and DT-PSMA loss was also analysed. RESULTS: Dose had a relative effect on BL SUV. For a population average gland (BL-SUV of 10), every 1 Gy increment, decreased the PT 1M/PT 6M-SUV by 1.6%/1.6% for PGs and by 0.9%/1.8% for SMGs. TD 50 of the population curves was 26.5/31.3 Gy for PGs, and 22.9/27.8 Gy for SMGs at PT 1M /PT 6M. PSMA loss correlated well with patient-reported xerostomia at DT/PT 1M (Spearman's ρ = -0.64, -0.50). CONCLUSION: A strong relationship was demonstrated between radiation dose and loss of secretory cells in salivary glands derived using PSMA PET/CT. The population curve could potentially be used as a dose planning objective, by maximising the predicted post-treatment SUV. BL scans could be used to further tailor this to individual patients.

KW - Dose response

KW - Head-and-neck cancer

KW - PET

KW - PSMA

KW - Salivary glands

KW - Toxicity

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U2 - 10.1016/j.radonc.2022.10.038

DO - 10.1016/j.radonc.2022.10.038

M3 - Article

C2 - 36368471

SN - 0167-8140

VL - 177

SP - 164

EP - 171

JO - Radiotherapy & Oncology

JF - Radiotherapy & Oncology

ER -

Dose response modelling of secretory cell loss in salivary glands using PSMA PET

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