Comment on a submandibular gland-sparing radiotherapy study: A methodological and statistical perspective

Abstract

The study by Garg et al., which employs ^99mTc-pertechnetate scintigraphy to evaluate submandibular gland function following radiotherapy for head and neck cancer, provides a useful exploration of objective functional assessment and contributes to advancing the field. While acknowledging its contributions, we suggest that several methodological and analytical aspects of the study could be further explored and refined. The study faced certain challenges in maintaining the sample, and the grouping approach may have introduced potential confounding factors. There remains room to further elucidate the standardization of scintigraphy procedures and their relationship with dose–response. The analytical strategy for longitudinal data could yield richer insights if temporal information were further explored. Additionally, the association between imaging outcomes and patients’ subjective experiences as well as long-term oncological safety would benefit from further investigation in subsequent research. Refinement in these areas would help to more comprehensively and robustly assess the clinical value of submandibular gland-sparing strategies. Future research that incorporates prospective designs, standardized multimodal assessment systems, patient-reported outcomes, and validation in real clinical settings would enhance the translatability and clinical relevance of this line of inquiry.

Dear Editor,

We read with great interest the article by Garg et al. titled “Evaluation of submandibular gland function using quantitative ^99mTc-pertechnetate scintigraphy in submandibular gland sparing radiotherapy for head-neck cancers, a prospective longitudinal study[1].” The authors present valuable longitudinal data on salivary gland function using scintigraphy, highlighting the benefits of submandibular gland (SMG) sparing. While the study is commendable for its focus on a less-studied gland, we would like to raise several methodological and analytical concerns that may affect the interpretation and generalizability of the findings.

First, The study began with 113 patients but only 80 were included in the final analysis, with only 11 in the spared group completing the 12-month assessment. Such a high attrition rate raises concerns about selection bias and the robustness of long-term conclusions. Furthermore, the non-randomized assignment to spared vs. unspared groups—based on clinical decisions regarding Level Ib irradiation—may introduce confounding. Although baseline differences in SEF were adjusted using ANCOVA, the small and uneven sample sizes limit the reliability of subgroup comparisons and dose–response modeling.

Second, While dynamic scintigraphy is a strengths of the study, details on standardization of patient preparation (e.g., hydration, positioning, sialogogue administration) are lacking. Variability in these factors could influence scintigraphic parameters. Additionally, the use of a fixed dose threshold of 39 Gy for SMG sparing relies on a single historic study. In the era of personalized radiotherapy, a dose–response analysis or validation of alternative thresholds would have been more informative[2].

Third, The use of aggregate cluster analysis for Umax is innovative, but the choice of geometric mean and median reporting for different endpoints complicates interpretation. More importantly, the longitudinal nature of the data was not fully exploited; repeated measures analysis (e.g., mixed-effects models) would be more appropriate to assess trends over time[3]. The lack of subgroup analysis, especially regarding chemotherapy, which is known to exacerbate salivary toxicity that represents a missed opportunity to identify modifiers of gland recovery.

Fourth,The study did not correlate scintigraphy findings with patient-reported outcomes (e.g., Xerostomia Questionnaire) or objective sialometry, limiting its clinical relevance. While the authors reported no recurrences near spared glands, the follow-up period (≤12 months) is too short to draw definitive conclusions about oncological safety. Longer-term tumor control data and details on target coverage compromises are needed to support the routine adoption of SMG sparing[4].

In conclusion, while Garg et al. provide promising evidence for SMG preservation, future studies should aim for larger, randomized cohorts, longer follow-up, integrated patient-reported outcomes, and more sophisticated statistical and dosimetric analyses. Such efforts will help translate scintigraphic findings into clinically meaningful practice guidelines.

Ethics Declarations

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Funding

This work was supported by the Joint Program of Liaoning Provincial Science and Technology Plan (Natural Science Foundation-General Program), China (Grant No. 2024-MSLH-320).

Declaration of competing interest

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