Page 129 - New epidemiological and PSMA-expression based paradigms in salivary gland tumors
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Tubarial salivary glands: A potential new organ at risk for radiotherapy
Gland characterization
In a human cadaver study (n=2), the designated area was dissected as 3x3x3cm blocks from bodies retrieved from a body donation program (AUMC, one male, one female). Tissue characteristics were assessed by histochemistry (H&E) and immunohistochemistry (PSMA, alpha-amylase). Immunohistochemistry was performed on a BenchMark Ultra autostainer, Ventana Medical Systems (VMS) (Methods 2 in the Supplementary material). Prostate (for PSMA) and parotid/ pancreas (for amylase) samples served as controls. Morphology and anatomical relations were evaluated by 3D-PDF digital reconstruction of anatomy using histological sections (10μm, 1/30). The visibility and anatomical features of the gland area on magnetic resonance imaging (Philips Achieve 3T MRI) were assessed in a healthy volunteer (Methods 3 in the Supplementary material).
Clinical relevance in oncology
The relation of RT dose to the designated area with reported toxicity was evaluated
using prospectively collected data from patients treated with curative RT, chemoradiation or bioradiation (accelerated RT+cetuximab) for HNC (UMCG
March 2007-June 2016; collected with patient consent in a study approved
by the ethical committee; https://clinicaltrials.gov: NCT02435576)[14]. All
patients received a CT-scan in a personalized immobilization mask in order to
define target volumes (including the primary tumor and lymph node metastasis)
and OARs (including the major salivary glands, and swallowing muscles, e.g. 8 pharyngeal constrictor muscle-PCM). This treatment planning aimed to deliver
the prescribed dose to the target volumes, while sparing the currently considered OARs. For this study, the location and configuration of the newly detected bilateral gland areas were retrospectively defined as additional OARs by deriving anatomical landmarks from the evaluated PSMA PET/CT and MRI scans, while also considering the cadaver-study findings. The cranial border was defined as the skull base caudally of the sphenoid sinus, and the caudal border as the level of the base of the uvula. The lateral border was defined as the skull base at the cranial side and fatty tissue at the caudal side. The anterior border was the skull base cranially and the dorsolateral pharyngeal wall caudally and the posterior border was the prevertebral long musculature. Delineation of this area was performed on the planning CT-scans of all patients, and its’ received radiation dose was determined.
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