Safety and Efficacy of Botulinum Toxin to Preserve Gland Function after Radiotherapy in Patients with Head and Neck Cancer: A Prospective, Randomized, Placebo-Controlled, Double-Blinded Phase I Clinical Trial

Abstract

This prospective, randomized, placebo-controlled, double-blinded phase I clinical trial investigates safety and efficacy of botulinum toxin (BoNT) to preserve gland function after radiotherapy in patients with head and neck cancer. Twelve patients with advanced head and neck cancer were injected with BoNT into the submandibular glands prior to primary radiochemotherapy. Six patients received BoNT/A and 6 patients BoNT/A and B, half of each subgroup into their left and the other half into their right gland. As an internal control, sodium chloride was injected into the respective contralateral gland (placebo). For the evaluation of the salivary gland function, technetium pertechnetate salivary gland scintigraphy was performed before and after the end of radiotherapy. BoNT/A and B were well tolerated. Analysis of the scintigraphic data revealed no statistically significant difference between BoNT and placebo regarding the scintigraphic uptake difference (pBoNT/A = 0.84 and pBoNT/A-B = 0.56 for BoNT/A vs. placebo and BoNT/A-B vs. placebo, respectively). We also found no significant difference in treatment between BoNT and placebo in terms of salivary excretion fraction (pBoNT/A = 0.44; pBoNT/A-B = 0.44). This study demonstrates that BoNT can be safely combined with radiochemotherapy. Dosing and timing of BoNT injection should be further investigated for efficacy analysis.Trial RegistrationGerman Registry for Clinical Trails DRKS00004595

Salivary Gland Toxicity of PSMA Radioligand Therapy: Relevance and Preventive Strategies

“…Other radioprotectors have also been tested, such as histamine, vitamin E, statins, and amifostine, exploiting mechanisms of radiation resistance. In humans, Teymoortash et al investigated the effect of botulinum toxin injections to the SGs with head and neck cancer undergoing external-beam radiotherapy (12). Earlier this year, our group translated that approach into tracer uptake blockade and achieved a 64% decrease in 68 Ga-PSMA uptake in an injected parotid gland, leading to the first proof-of-concept publication on the topic (13) and heralding a hypothesis of nonspecific tracer accumulation.…”

Injection of Botulinum Toxin for Preventing Salivary Gland Toxicity after PSMA Radioligand Therapy: an Empirical Proof of a Promising Concept

“…A 63-year-old patient with advanced metastatic castrationresistant prostate cancer underwent 68 Ga-PSMA PET/CT imaging before and 45 days after receiving multifocal, ultrasound-guided injections of a total of 80 units botulinum toxin A into the right parotid gland (Fig. 1) according to a clinically approved method used in patients who have suffered from sialorrhoea for over two decades [1][2][3]. The SUVmean of the radioligand in the injected parotid gland showed a highly significant decrease of up to 60% compared with the left side, especially in the pars profunda of the gland, and a decrease of up to 64%, but no significant change in the left parotid gland, compared with the baseline PET/CT study.…”

Competitive blocking of salivary gland [18F]DCFPyL uptake via localized, retrograde ductal injection of non-radioactive DCFPyL: a preclinical study

“…Although some initial improvement was observed, it was unclear whether the effect was due to saline irrigation or administration of the steroids. Encouraging results were also observed in a preclinical and clinical trial evaluating botulinum toxin A; however, further investigation in more patients is needed to determine the dosing and timing of botulinum injection and the possibility of long-term SG damage from the botulinum injection itself should be carefully considered [27,28]. In a preclinical PCa tumor model, monosodium glutamate (MSG) showed reduced uptake of 68 Ga-PSMA-11 in SGs and kidney without affecting tumor uptake [29].…”