The Use of Pre-Chemoradiotherapy Total Masseter Muscle Volume as a Novel Predictor of Radiation-Induced Trismus in Locally Advanced Nasopharyngeal Carcinoma Patients

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Dear authors, I had the opportunity to review your interesting manuscript. Please include some remarks, whether the masseter volume might also be of importance for other ENT tumors. Or is it specific for the tumor type included only? Kind regards.

Comments on the Quality of English Language

Fine, minor spelling errors, please correct.

Author Response

We thank Reviewer 1 for his/her constitutive suggestions

Comment 1. Dear authors, I had the opportunity to review your interesting manuscript. Please include some remarks, whether the masseter volume might also be of importance for other ENT tumors. Or is it specific for the tumor type included only? Kind regards.

Response 1. Although answering this question is challenging in the lack of data in other tumor locations, we feel that any loss in masseter muscle volume, the strongest masticatory muscle, reflects the patient's poor nutritional condition on the route to cancer cachexia. Therefore, it may predict trismus and, probably, other severe toxicities after any cancer treatment in patients with different head and neck cancers. Furthermore, it may also be beneficial in predicting prognosis, as previously demonstrated in patients with locally advanced nasopharyngeal cancer (Pehlivan, U.A.; Somay, E.; Yilmaz, B.; Besen, A.A.; Mertsoylu, H.; Selek, U.; Topkan, E. Pretreatment Masseter Muscle Volume Predicts Survival in Locally Advanced Nasopharyngeal Carcinoma Patients Treated with Concurrent Chemoradiotherapy. J Clin Med. 2023,12, pp.6863.). However, this requires further well-designed studies to address the issue. This issue has been discussed as an additional drawback of the study in the revised Limitations section.

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

In this study, the authors validated the hypothesis that pretreatment total masseter muscle volume (TMMV) measures can predict radiation-induced trismus (RIT) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) receiving concurrent chemoradiotherapy (C-CRT). The results showed that The presence of a smaller pretreatment TMMV is a reliable and independent biological marker that can predict higher RIT rates in LA-NPC patients who receive C-CRT. This study is of clinical value. However, the writing can be improved.

 

1.   Line 87. The project no. is missing.

2.   Line 141. “Statistical analysis” should be “2.5. Statistical analysis”.

3.   Figure 1. The size of the fonts can be increased.

4.   Discussion. The limitations of this study and future work should be described.

5.   Institutional Review Board Statement. The IRB approval date should be provided.

6.   References. The formats of the references should follow the journal requirements.

7.   The English writing can be improved.

Comments on the Quality of English Language

In this study, the authors validated the hypothesis that pretreatment total masseter muscle volume (TMMV) measures can predict radiation-induced trismus (RIT) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) receiving concurrent chemoradiotherapy (C-CRT). The results showed that The presence of a smaller pretreatment TMMV is a reliable and independent biological marker that can predict higher RIT rates in LA-NPC patients who receive C-CRT. This study is of clinical value. However, the writing can be improved.

 

1.   Line 87. The project no. is missing.

2.   Line 141. “Statistical analysis” should be “2.5. Statistical analysis”.

3.   Figure 1. The size of the fonts can be increased.

4.   Discussion. The limitations of this study and future work should be described.

5.   Institutional Review Board Statement. The IRB approval date should be provided.

6.   References. The formats of the references should follow the journal requirements.

7.   The English writing can be improved.

Author Response

We thank to Reviewer 2 for his/her valuable suggestions.

Comment 1. Line 87. The project no. is missing

Response 1. The project no is now provided in the revised manuscript.

Comment 2. Line 141. “Statistical analysis” should be “2.5. Statistical analysis”

Response 2. It is corrected as recommended.

Comment 3. Figure 1. The size of the fonts can be increased

Response 3. Based on the suggestion, the figure has been revised, and the fonts have been increased for better visibility.

Comment 4. Discussion. The limitations of this study and future work should be described

Response 4. The limitations section has been revised and expanded as per the recommendations.

Comment 5. Institutional Review Board Statement. The IRB approval date should be provided.

Response 5. The date of approval by the Institutional Review Board has now been specified in the Institutional Review Board Statement section.

Comment 6.   References. The formats of the references should follow the journal requirements.

Response 6. All references are now revised to comply with the journal requirements.

Comment 7. The English writing can be improved.

Response 7. A professional Editing company has now rechecked the entire manuscript to improve the specified issue.

 

Author Response File: Author Response.docx

Reviewer 3 Report

Comments and Suggestions for Authors

This well written paper identifies a masseter muscle volume of 35 cc or less as a risk factor for CRT-induced Trismus in nasopharyngeal carcinoma. The paper is valuable not only to radiologists, but also to otolaryngologists and head and neck surgeons. Although sufficient number of cases and well discussed, there are several points that need to be revised for publication.

First, the authors need to take into account the involvement or irradiation to the pterygoid muscle as a cause of the CRT-induced Trismus. Usually, irradiation of the irradiation of the pterygoid muscle or tumor invasion results in a strong CRT-induced Trismus. Authors should take this factor into account when performing multivariate analysis.

Second, the method of measuring masseter muscle is not clear. It would be extremely helpful to the reader if it were possible to show the calculation process and the image processing during the measurement as figures.

Comments on the Quality of English Language

There is no problem with the quality of English.

Author Response

Reviewer 3

We thank Reviewer 3 for his/her valuable suggestions.

Comment 1. First, the authors need to take into account the involvement or irradiation to the pterygoid muscle as a cause of the CRT-induced Trismus. Usually, irradiation of the irradiation of the pterygoid muscle or tumor invasion results in a strong CRT-induced Trismus. Authors should take this factor into account when performing multivariate analysis.

Response 1. None of the eligible patients in this study had invasion of pterygoid or other masticatory muscles. Our previous studies demonstrated that masticatory apparatus volume receiving various doses, including the pterygoid muscle, were predictive of trismus (Topkan E, Somay E, Yilmaz B, Pehlivan B, Selek U. Valero's host index is useful in predicting radiation-induced trismus and osteoradionecrosis of the jaw risks in locally advanced nasopharyngeal carcinoma patients. BMC Cancer. 2023 Jul 12;23(1):651.; Somay E, Yilmaz B, Topkan E, Pehlivan B, Selek U. Low hemoglobin levels predict increased radiation-induced trismus rates in nasopharyngeal cancer. Oral Dis. 2023 May 8. doi: 10.1111/odi.14605.). The primary focus of this study was to investigate the baseline factors that may influence the trismus rates after concurrent chemoradiotherapy rather than the impact of RT on specific muscles. However, up to the reviewer’s recommendation, the absence of medial and lateral pterygoid and temporalis muscles or the volume of all the masticatory muscles as a single structure is now specified as an additional study limitation.

Comment 2. Second, the method of measuring masseter muscle is not clear. It would be extremely helpful to the reader if it were possible to show the calculation process and the image processing during the measurement as figures.

Response 2. A figure illustrating the masseter muscle delineation process and the method used for volume calculations is now included in the revised manuscript.

 

Author Response File: Author Response.docx

Round 2

Reviewer 3 Report

Comments and Suggestions for Authors

The authors replied to my questions sincerely.

This article is now worthy of publication.