Survival in Patients with Primary Parotid Gland Carcinoma after Surgery—Results of a Single-Centre Study

Round 1

Reviewer 1 Report

The current article presented a novel description of the survival in patients with primary parotid gland carcinoma after surgery in terms of five-year overall survival (OS), disease-specific survival (DSS), local relapse free survival (LRFS) and distant metastasis-free survival (DMFS). Also, the risk and the prognostic factors affecting patient outcomes have been analyzed. All the sections of the article have been well described. Below are some suggestions for the authors.

Introduction:

*Introduction section is concise and short. Authors may add some text about already known material on the subject.

*Correct grammar mistake in line 39.

Result:

*Describe abbreviations used in Table 3. e.g., NOS

Discussion:

*<Molteni et al. observed that an age at diagnosis greater than 55 years was a cause of poorer disease survival. However, in our cohort, age was not associated with worse DSS, LRFS or DMFS.>. In your opinion, what may be the reason for this difference between the results?

Conclusion:

*Which alternative treatments may be applied in patients with poor prognosis despite the use of surgical and radiotherapy?

Author Response

1) Introduction section is concise and short. Authors may add some text about already known material on the subject.

The authors added some information in this section. 

2) Correct grammar mistake in line 39.

Done.

3) Describe abbreviations used in Table 3. e.g., NOS

Done.

4) <Molteni et al. observed that an age at diagnosis greater than 55 years was a cause of poorer disease survival. However, in our cohort, age was not associated with worse DSS, LRFS or DMFS.>. In your opinion, what may be the reason for this difference between the results?

The data presented by Molteni et al showed that age was associated with poorer DSS even though not affecting the risk of developing recurrences. According to their findings, the reason could be in the different distribution of the histotypes and of the localization of the SGM between over 55 and under 55 years patients. We believe that in our cohort comorbidities (and, therefore, performance status), histological types and oncological stages were more homogeneously distributed in both groups. Therefore, age alone was not associated with a poorer prognosis.

The authors discussed this point in the revised version of the manuscript as follows:

“in our cohort of patients, comorbidities (and, therefore, performance status), histological types and oncological stages were more homogeneously distributed in both groups, as a consequence, age alone was not associated with a poorer prognosis”.

5) Which alternative treatments may be applied in patients with poor prognosis despite the use of surgery and radiotherapy?

The authors added some information about chemotherapy, target therapy and immunotherapy in the revised version of the manuscript (see lines 344-351).

“The prognosis in case of inoperable, recurrent and metastatic disease remains poor. In such cases different systemic therapeutic options are available. Recently, targeted therapies (e.g., antibodies against c-Kit, EGFR, VEGFR, ErbB2/HER-2) have been introduced when tumor-specific targets are available. However, no randomized controlled trials compare survival outcomes between different targeted systemic therapies in patients with salivary gland carcinomas. Chemotherapy can be always used, while few clinical trials have been conducted regarding the efficacy of immunotherapy targeting PD-1/PD-L1 and CTLA-4.”

 

Please see in attachment the reviewed manuscript.

Author Response File: Author Response.docx

Reviewer 2 Report

The authors retrospectively analyzed the clinical data of the patients with primary parotid gland cancer they treated. The results indicated  high-risk histology, stage IV disease, LVI, PNI, node metastasis, skin involvement, FN involvement and positive or close margins are associated with poorer prognoses. Results seem interesting, but some issues should be reconsidered.

 

Table 5 can involve a risk of multiple comparisons problem. Multivariate analyses should be performed to find true risk factors from the candidates of univariate analyses.

 

Table 1, TC in preoperative work-up means CT?

 

Table 1, Clinical nerve involvement includes No, Yes, and No. Their percentages can not sum up to 100%.

 

Table 1, In Adjuvant treatment, total number is not 65.

 

Line 130-141, Forty-seven + Four + Nine + two = 62. How about other three patients?

 

Line 160, mean follow-up is 3.5 years. In such situation, median should be shown because follow-up period can not follow a normal distribution. If median follow-up is too short, their 5-year survival can be different from true survival, because they employed recent patients of 2017-2022.

 

Line 174-, "High-risk histology and T3 and T4 stages were associated with a higher incidence of neck metastasis (Table 3)." The significance should be indicated as asterisks.

 

Line 210-, "FNAC has become a standard diagnostic test of parotid masses, with an overall di- agnostic accuracy of 96% (95% CI, 94–97%) in distinguishing benign from malignant parotid tumours. " This needs  a reference.

 

Author Response

1) Table 5 can involve a risk of multiple comparisons problems. Multivariate analyses should be performed to find true risk factors from the candidates of univariate analyses.

Because of the low number of cases (dead of disease), our multivariate analysis does not reach high statistical significance and we do not consider it worth of publishing. Please see the attached word file with the multivariate analysis.

2) Table 1, TC in preoperative work-up means CT?

The acronym “TC” in preoperative work-up means CT. The authors modified the revised version of the manuscript accordingly.

3) Table 1, Clinical nerve involvement includes No, Yes, and No. Their percentages can not sum up to 100%.

The table was sent with the correct numbers, but the automatic editing system shifted a line. It was not due to our negligence.

4) Table 1, In Adjuvant treatment, total number is not 65.

The table was sent with the correct numbers, but the automatic editing system shifted a line. It was not due to our negligence.

In this particular case, the total is 64 because we consider as 1 case the patient with bilateral disease.

5) Line 144-155, Forty-seven + Four + Nine + two = 62. How about other three patients?

The authors apologize for the typo. The total is 64 because one patient with preoperative grade III facial palsy because of a previous parotidectomy performed in another institution was excluded from the analysis of FN outcomes.

6) Line 173-174, mean follow-up is 3.5 years. In such situation, median should be shown because follow-up period can not follow a normal distribution. If median follow-up is too short, their 5-year survival can be different from true survival, because they employed recent patients of 2017-2022.

In our analysis, the mean follow-up was 3.57 years and the median follow-up was 3.61 years. We added this information in the main text of the revised version of the manuscript.

7) Line 188 -, "High-risk histology and T3 and T4 stages were associated with a higher incidence of neck metastasis (Table 3)." The significance should be indicated as asterisks.

The revised version of the manuscript was modified as follows:

“High-risk histology (31.6% versus 10.9%, p<0.05) and T3-T4 stages in low-risk histotypes (33% versus 2.9%, p<0.05) were associated with a higher incidence of neck metastasis”

8) Line 245-, "FNAC has become a standard diagnostic test of parotid masses, with an overall di- agnostic accuracy of 96% (95% CI, 94–97%) in distinguishing benign from malignant parotid tumours. " This needs a reference.

The revised version of the manuscript was modified as follows:

“FNAC has become a standard diagnostic test of parotid masses, with an overall diagnostic accuracy of 96% (95% CI, 94–97%) in distinguishing benign from malignant parotid tumours [13].”

Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

The authors addressed all of the reviewers' comments, leading to a refined article. However, Some issues need to be reconsidered before acceptance.

 

1. In Table 5, univariate analyses are repeated, including multiple comparisons problem. The p-values should be corrected using e.g. Bonferroni method. Some p-values may lose significance.

 

2. The reasons should be described in Discussion part why the authors do not show the results of multivariate analyses. Univariate analyses have less scientific power to support their conclusions. They must indicate the disadvantage of this study clearly.

Author Response

1. In Table 5, univariate analyses are repeated, including multiple comparisons problem. The p-values should be corrected using e.g. Bonferroni method. Some p-values may lose significance.

The authors used the Bonferroni method to evaluate the reliability of multiple comparisons (stage of disease, margin status and tumor’s size) in order to control the family-wise error rate.  The authors also modified the table 5 adding the new data. Please see the new version of the manuscript.

2. The reasons should be described in Discussion part why the authors do not show the results of multivariate analyses. Univariate analyses have less scientific power to support their conclusions. They must indicate the disadvantage of this study clearly.

The authors explained the disadvantage of this study in the discussion. Please see the new version of the manuscript. 

Author Response File: Author Response.docx