Response to “comment on a submandibular gland-sparing radiotherapy study: a methodological and analytical perspective”

Abstract

We thank the authors for their interest and constructive comments on our study. This response clarifies methodological aspects and the scope of our work evaluating scintigraphic assessment of irradiated submandibular glands. The study was initiated during the COVID-19 pandemic, resulting in patient dropouts and limiting stratified analyses due to small subgroup sizes. Nevertheless, our cohort includes scintigraphy data from 27 spared and 53 unspared submandibular glands, representing a comparatively large dataset for long-term functional evaluation. Scintigraphy protocols were standardized to minimize technical variability, although unavoidable physiological and patient-related factors may have influenced measurements. The primary aim was to characterize scintigraphic parameters following irradiation; analyses of dose–response relationships, temporal modeling, and correlations with patient-reported xerostomia outcomes are ongoing. With a median follow-up of three years, no locoregional recurrences were observed near spared glands, supporting the oncological safety of submandibular gland sparing.

We sincerely thank the authors for their interest in our article and for their valuable insights. All comments were carefully considered, and we provide our responses below.

The study was initiated during the COVID-19 pandemic, which resulted in patient dropouts at various time points. We acknowledge that this may have introduced potential confounding factors, and stratified analyses based on gender, performance status, chemotherapy status, and body mass index could not be performed due to insufficient sample sizes in the different strata across follow-up intervals. Most previous studies evaluating submandibular gland sparing using functional imaging have included relatively small cohorts. The study by Murthy et al had a comparable sample size; however, they did not attempt to spare the submandibular glands [1]. In comparison, our study includes scintigraphy data from 27 spared and 53 unspared submandibular glands, representing a comparatively larger dataset for long-term functional evaluation and providing a unique and detailed scintigraphic assessment of both spared and unspared submandibular glands.

Scintigraphy procedures were standardised with respect to patient preparation, radiotracer administration, image acquisition, and region-of-interest delineation to minimize technical variability. However, certain factors, including patient hydration status, physiological variability, medication use, compliance with pre-scan instructions, and minor positioning differences, were difficult to fully standardise and may have influenced scintigraphic measurements.

The primary aim of this study was to characterise scintigraphic parameters in irradiated submandibular glands. We are currently analyzing dose–response relationships using both subjective and objective parameters. Further temporal analysis using generalised linear mixed models, which account for repeated measurements and within-subject correlations over time, will be reported in a subsequent publication. Patient-reported outcomes were assessed using a validated xerostomia questionnaire, and their correlation with scintigraphic parameters will also be presented in future work.

With respect to oncological safety, no locoregional recurrences were observed in the vicinity of the spared submandibular gland, with a median follow-up of three years. This finding is consistent with the study by Hoyne et al., who demonstrated that reducing the mean dose to the contralateral submandibular gland to ≤39 Gy did not compromise target volume coverage [2].

The present study was conducted using a prospective design, and scintigraphic parameters were standardised wherever reasonably feasible. Patient-reported outcomes were also incorporated to enhance the clinical relevance and translatability of our findings.

We hope that these responses adequately address the concerns raised. We would be pleased to respond to any further comments or queries.

Funding/financial support

JIPMER, Puducherry.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.