Comment on “The Role of Immunotherapy in Salivary Gland Cancer: A Systematic Review”

Dear Editor,

We read with great interest the article titled “The Role of Immunotherapy in Salivary Gland Cancer: A Systematic Review” by Kim et al. ¹ The authors present a timely and valuable review that explores the potential of immunotherapy, particularly immune checkpoint inhibitors (ICIs), in the management of recurrent and metastatic salivary gland cancer (SGC). Given the challenges in treating these rare malignancies, the study significantly contributes to the growing body of evidence in this area, shedding light on the promising role of immunotherapy for patients with advanced SGC. This study is particularly important as it addresses a critical gap in the literature, providing much-needed insights into the potential benefits of ICIs in a disease for which effective treatment options are severely limited. The authors have compiled and synthesized data from multiple sources, offering a more robust and comprehensive understanding of the current therapeutic landscape for SGC.

However, we would like to raise a few points for consideration regarding the methodological approach used in this review, which could enhance the clarity and transparency of the findings. First, the authors mention that a risk of bias assessment was conducted for the included studies. We agree that assessing the risk of bias is crucial in ensuring the robustness of the findings, particularly when combining different study designs, such as Randomized Controlled Trials (RCTs) and observational studies. While the authors indicate that this assessment was performed, the methodology used to assess bias is not fully outlined. In particular, the Cochrane Risk of Bias 2 tool should have been employed for the RCTs to assess domains such as randomization, blinding, and selective reporting, as recommended by the Cochrane Collaboration. ² Additionally, for observational studies, we suggest that the Newcastle-Ottawa Scale be used,^3,4 or alternatively, the ROBINS-I tool for nonrandomized studies. Clearly specifying the tools and criteria used would enhance the transparency and reproducibility of the review, providing readers with a clearer understanding of the quality of the studies included.

Second, while the authors mention that the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was utilized to assess the certainty of the evidence, we found that the results of the GRADE assessment are not presented in the article. In particular, it would be helpful if the authors could clarify the certainty of the evidence for each outcome, such as overall survival, progression-free survival, and adverse events. A more detailed explanation of how the GRADE system was applied, and the level of certainty for each outcome would allow readers to better interpret the strength of the evidence and the potential implications of the findings evidence. ⁵ It is crucial to transparently report how GRADE was applied, including any downgrades due to study limitations, risk of bias, or imprecision, as this would strengthen the conclusions drawn from the systematic review.

While the authors’ findings suggest that anti-PD1 inhibitors like pembrolizumab and nivolumab can offer potential benefits for patients with advanced SGC, we feel it is important to emphasize the need for further investigation into the biomarkers that could predict which patients will respond to ICIs. This point is crucial given the heterogeneity of SGC, which includes various histological subtypes with potentially different responses to immunotherapy. Stratifying patients based on tumor characteristics, such as PD-L1 expression and tumor mutational burden, could significantly improve our understanding of which subgroups may derive the most benefit from these treatments. We also believe that the exploration of combination therapies, as discussed in the study, warrants further research to determine the most effective regimens for patients with SGC.

We applaud the authors for their thorough and timely systematic review, which provides important insights into the potential role of immunotherapy for recurrent and metastatic SGCs. The study is a significant contribution to the field and sets the stage for further research into immunotherapeutic strategies for this challenging disease. We hope that future studies will address the methodological points mentioned above, including more comprehensive reporting on risk of bias assessments, GRADE certainty assessments, and the identification of predictive biomarkers, to further refine our understanding of the role of immunotherapy in the treatment of SGC.

Shubham Kumar, MScDepartment of Oncology, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India Ranjana Sah, MDDepartment of Paediatrics, Dr D. Y. Patil Medical College Hospital and Research Centre, Dr D. Y. Patil Vidyapeeth (Deemed-to-Be-University), Pimpri, Pune, Maharashtra, IndiaDepartment of Public Health Dentistry, Dr D. Y. Patil Medical College Hospital and Research Centre, Dr D. Y. Patil Vidyapeeth (Deemed-to-Be-University), Pimpri, Pune, Maharashtra, IndiaMedical Laboratories Techniques Department, AL-Mustaqbal University, Hillah, Babil, Iraq Rachana Mehta, MDClinical Microbiology, RDC, Manav Rachna International Institute of Research and Studies, Faridabad, Haryana, India