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

Vineet Mohan; Natascha M. Bruin; Roel J.H.M. Steenbakkers; Walter Noordzij; Chris H.J. Terhaard; Bart de Keizer; Abrahim Al-Mamgani; Jeroen B. van de Kamer; Jan Jakob Sonke; Wouter V. Vogel

doi:10.1016/j.radonc.2022.10.038

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

Vineet Mohan, Natascha M. Bruin, Roel J.H.M. Steenbakkers, Walter Noordzij, Chris H.J. Terhaard, Bart de Keizer, Abrahim Al-Mamgani, Jeroen B. van de Kamer, Jan Jakob Sonke, Wouter V. Vogel^*

^*Corresponding author for this work

Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE)

Research output: Contribution to journal › Article › Academic › peer-review

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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: 28H&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. TD₅₀ 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 and 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{3f01d6fe759942f6a20d1a2d2559f1ef,

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: 28H&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 (PT1M/PT6M). Dose, BL- PT1M- and PT6M-SUV were extracted for every voxel inside each parotid (PG) and submandibular (SMG) gland. The PT1M/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 PT1M/PT6M-SUV by 1.6 %/1.6 % for PGs and by 0.9 %/1.8 % for SMGs. TD50 of the population curves was 26.5/31.3 Gy for PGs, and 22.9/27.8 Gy for SMGs at PT1M /PT6M. PSMA loss correlated well with patient-reported xerostomia at DT/PT1M (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 = "Vineet Mohan and Bruin, {Natascha M.} and Steenbakkers, {Roel J.H.M.} and Walter Noordzij and Terhaard, {Chris H.J.} and {de Keizer}, Bart and Abrahim Al-Mamgani and {van de Kamer}, {Jeroen B.} and Sonke, {Jan Jakob} and Vogel, {Wouter 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 and 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, Vineet

AU - Bruin, Natascha M.

AU - Steenbakkers, Roel J.H.M.

AU - Noordzij, Walter

AU - Terhaard, Chris H.J.

AU - de Keizer, Bart

AU - Al-Mamgani, Abrahim

AU - van de Kamer, Jeroen B.

AU - Sonke, Jan Jakob

AU - Vogel, Wouter 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: 28H&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 (PT1M/PT6M). Dose, BL- PT1M- and PT6M-SUV were extracted for every voxel inside each parotid (PG) and submandibular (SMG) gland. The PT1M/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 PT1M/PT6M-SUV by 1.6 %/1.6 % for PGs and by 0.9 %/1.8 % for SMGs. TD50 of the population curves was 26.5/31.3 Gy for PGs, and 22.9/27.8 Gy for SMGs at PT1M /PT6M. PSMA loss correlated well with patient-reported xerostomia at DT/PT1M (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: 28H&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 (PT1M/PT6M). Dose, BL- PT1M- and PT6M-SUV were extracted for every voxel inside each parotid (PG) and submandibular (SMG) gland. The PT1M/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 PT1M/PT6M-SUV by 1.6 %/1.6 % for PGs and by 0.9 %/1.8 % for SMGs. TD50 of the population curves was 26.5/31.3 Gy for PGs, and 22.9/27.8 Gy for SMGs at PT1M /PT6M. PSMA loss correlated well with patient-reported xerostomia at DT/PT1M (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

U2 - 10.1016/j.radonc.2022.10.038

DO - 10.1016/j.radonc.2022.10.038

M3 - Article

C2 - 36368471

AN - SCOPUS:85141976121

SN - 0167-8140

VL - 177

SP - 164

EP - 171

JO - Radiotherapy and Oncology

JF - Radiotherapy and Oncology

ER -

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

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