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

Radiother Oncol. 2022 Dec:177:164-171. doi: 10.1016/j.radonc.2022.10.038. Epub 2022 Nov 8.

Affiliations

¹ Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
² Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
³ Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
⁴ Department of Radiotherapy, University Medical Center Utrecht, Utrecht, the Netherlands.
⁵ Department of Nuclear Medicine and Radiology, University Medical Center Utrecht, Utrecht, the Netherlands.
⁶ Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
⁷ Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam, the Netherlands. Electronic address: w.vogel@nki.nl.

PMID: 36368471
DOI: 10.1016/j.radonc.2022.10.038

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.

Keywords: Dose response; Head-and-neck cancer; PET; PSMA; Salivary glands; Toxicity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Head and Neck Neoplasms* / diagnostic imaging
Head and Neck Neoplasms* / metabolism
Head and Neck Neoplasms* / radiotherapy
Humans
Male
Positron Emission Tomography Computed Tomography
Positron-Emission Tomography
Salivary Glands / diagnostic imaging
Xerostomia* / diagnostic imaging
Xerostomia* / etiology