Variation in Body Mass and Skeletal Muscle Indices in Head and Neck Cancer Patients Undergoing (Chemo)Radiotherapy and Nutritional Intervention

Round 1

Reviewer 1 Report

I carefully reviewed the manuscript ID-2080612, entitled as” Variations in body mass and skeletal muscle indices in head and neck cancer patients undergoing (chemo)radiotherapy and nutritional intervention " submitted by Pisani, C. et al. In overall, the results are not convincing enough and had major flaws in study designs, analysis and discussion.

1.     The major flaw of the current study is heterogenous enrollment including varied tumor stages, tumor sites and treatment modalities that could all affect post-treatment nutrition status and muscle mass.

2.     The authors did not explain why SMI is better than BMI.

3.     Some references are inappropriately cited.

(1)   Reference 1 only showed stage I-II laryngeal cancer. The age of laryngeal cancer is somewhat older than other head and neck cancer.

(2)   Reference 9 to support that SMI at C3 level could offer similar equality to that measured at L3 level. This reference is not convincing enough, either. This a review article.

4.     Inclusion criteria should describe surgical condition before enrollment, which indeed affects the nutritional assessment.

5.     Based on ESPEN guideline authors applied to the current study, there were no data to show the real condition of calorie and protein supply of the patients in this manuscript.

6.     What is the definition of treatment interruption?

7.     There are some ambiguous and subjective statements in the discussion.

(1)    Why could accurate assessment and early nutrition intervention explain that the strength of SMI is better than BMI?

(2)   How many patients received early nutrition intervention? What kinds of nutrition intervention?

(3)   More information regarding nutrition supply stratified by stages is recommended.

8.     Why would inflammation assessment further confirm the hypothesis?

Author Response

Please see the attachment

Author Response File: Author Response.docx

Reviewer 2 Report

This is an interesting study, and though not much significant results, the idea is novel. Few points to revise

1. The last line in the abstract is not conveying the whole message. Please rewrite

2. Please include the details about ethical approval in the methods section

3. Line 269 "Several literatures evidence " is not correct. Several such lines could be identified. Please rewrite

4. The authors need to rewrite a few sentences as many are grammatically wrong, lines 116-118,197 and many more. English language correction is required. The use of "the" is present in many areas

5. The authors can explore if there is any association between these indices tested and the survival of the patient. this has not been assessed in the manuscript?

6. Is there any association between acute mucosal toxicity and muscle mass? What is the significance of lines 259-261?? Please describe

Author Response

Reviewer 2

This is an interesting study, and though not much significant results, the idea is novel. Few points to revise

1. The last line in the abstract is not conveying the whole message. Please rewrite → We agree with reviewer’s comment. We have modified the last part of the abstract “According to our analysis, SMI variation seems to reflect the effect of an appropriate nutritional intervention and may represent a reliable, simple tool for muscle mass analysis.”
2. Please include the details about ethical approval in the methods section; our local ethics committee, “Comitato Etico Interaziendale Novara – AASSLL BI, NO, VCO, AOU “Maggiore della Carità” di Novara”, ruled that no formal ethics approval was required in this particular case because all the analysis was performed with no changes in patients’ treatments. The policy of our institution is to allow investigations on patients’ imaging for those who signed an informed consent for a radiotherapy procedure. As a matter of fact, the informed consent for any radiotherapy procedure includes a sentence in this regard. We added a sentence in material and method.
3. Line 269 "Several literatures evidence " is not correct. Several such lines could be identified. Please rewrite → The article has been extensively reviewed by a native speaker.
4. The authors need to rewrite a few sentences as many are grammatically wrong, lines 116-118,197 and many more. English language correction is required. The use of "the" is present in many areas;The manuscript has been deeply reviewed by one of the authors (Federico Mastroleo), who is a native bilingual speaker.
5. The authors can explore if there is any association between these indices tested and the survival of the patient. this has not been assessed in the manuscript. → We thank the reviewer for the valuable adice. It would have been interesting to explore this aspect but, due the the scarcity of the sample and the heterogeneity of the follow-up, we are not able to perform such analysis. The aim of future analysis would be to correlate these indices with survival parameters (OS and PFS)

6. Is there any association between acute mucosal toxicity and muscle mass? What is the significance of lines 259-261?? Please describe →  We have added a sentence in lines 286-289 and two references “Current evidences show that chronic low-grade inflammation, such as mucosal toxicity related to radiotherapy, actively contributes to the loss of muscle mass, strength and functionality, leading to sarcopenic status especially in elderlies [Dalle S 2017, Churchward-venne 2012].”

Reviewer 3 Report

The authors have conducted a study to address the effect on body mass and skeletal muscle indices in a retrospective cohort of patients with head and neck squamous cell cancer who underwent RT or RT-CHT plus nutritional intervention. 

Minor Comments:

1. Lane 28 (Abstract) "BMI fluctuations doesn’t correlate with muscle mass variations". There is not evidence of any clear analysis to assess this correlation.

2. Methods: How was the sample size calculated?

3. Lane 156: To replace "P" value with "p" value.

4. Lane 160 (Results): "Median age was 62 years". However, in table 1, age is reported like as the mean (61 years).

5. None of values reported in table 2 represent the mean ±SD.

Author Response

Reviewer 3

The authors have conducted a study to address the effect on body mass and skeletal muscle indices in a retrospective cohort of patients with head and neck squamous cell cancer who underwent RT or RT-CHT plus nutritional intervention. 

Minor Comments:

1. Lane 28 (Abstract) "BMI fluctuations doesn’t correlate with muscle mass variations". There is not evidence of any clear analysis to assess this correlation. Thank you for this comment; we know that probably this sentence suggests misunderstandings, so we decided to deleted it.
2. Methods: How was the sample size calculated? We defined the sample size in study population paragraph. “We considered all HNSCC patients treated at our Institution by RT or RT-CHT within a definitive or adjuvant setting between 2016 and 2020. Inclusion criteria were: HNSCC diagnosis, treatment with RT or RT-CHT, presence of a pre-treatment CT scan (CT t0) and a CT scan 3 months after treatment completion (CT t3) performed at our Institution, baseline nutritional evaluation which continued throughout and after the treatment. Patients without required clinical data, treated in palliative setting, or with CT imaging performed outside our institution were excluded. For patients treated in adjuvant setting, all patients performed a basal nutritional evaluation before surgery. RT started within 6 weeks of surgery. With these criteria, we selected the consecutive 73 patients treated between 2016 and 2020.”
3. Lane 156: To replace "P" value with "p" value. We corrected it
4. Lane 160 (Results): "Median age was 62 years". However, in table 1, age is reported like as the mean (61 years).  We thank the reviewer for this check. We verified this data, and we corrected it.
5. None of values reported in table 2 represent the mean ±SD → we modified header table with the correct “mean (±SD)”

Reviewer 4 Report

The comments and observations are included in the attached manuscript.

Comments for author File: Comments.pdf

Author Response

We agree with all your comments, and we have incorporated your suggestions throughout the manuscript. The manuscript has been fully reviewed by a native speaker.

Round 2

Reviewer 1 Report

The authors have answered my concern clearly.  There is no more comment.

Author Response

We deeply appreciate the time and effort that you have dedicated to provide this feedback on the manuscript.

Reviewer 2 Report

Nil

Author Response

We deeply appreciate the time and effort that you have dedicated to provide this feedback on the manuscript.

We rephrased some sentences.

Reviewer 3 Report

 The authors have done a good job of addressing my concerns. However, there are still some errors in the way of displaying the data:

1.Lane 181 (Results): "Median age was 62 years."However, in table 1, age is reported as the mean.The value they want to display must be either the median or the mean, but it cannot be both for this case.

2. The error in table 2 persists. None of the values ​​reported here represents the mean ±SD, not the way they were written.

Author Response

We deeply appreciate the time and effort that you  have dedicated to provide a valuable feedback on this manuscript

1.Lane 181 (Results): "Median age was 62 years."However, in table 1, age is reported as the mean.The value they want to display must be either the median or the mean, but it cannot be both for this case  --> we checked this data. The value represents the Mean value. We corrected the text. 

2. The error in table 2 persists. None of the values ​​reported here represents the mean ±SD, not the way they were written. --> we corrected the table. We hope we understood reviewer's request correctly.

Reviewer 4 Report

The corrections/modifications have been done according to the observations of the reviewers.However,there are still minor spell checks/Grammatical errors and a few incoherent sentences which needs to be rewritten and are highlighted in the attached manuscript.

Comments for author File: Comments.pdf

Author Response

We deeply appreciate the time and effort that you have dedicated to provide a valuable feedback on this manuscript. We have been able to incorporate changes to reflect all of the suggestions provided.