A Study of Peripheral Blood Parameters to Predict Response to Induction Chemotherapy and Overall Survival in Advanced Laryngeal Squamous Cell Carcinoma

Round 1

Reviewer 1 Report

The authors retrospectively analyzed peripheral blood parameters to find predictive factors for IC response using their LSCC cohort. They demonstrated that the Blood Logistic Model was superior to TNM stage model to predict IC response. They combined the peripheral blood parameters with clinical information, making Blood-Clinical model to predict OS of LSCC. Besides, their analyses demonstrated that IC improved laryngeal function preservation without reducing survival prognosis.

Their report is very interesting for head and neck oncologists and could lead to a novel prospective study including IC.

Some minor issues should be reconsidered.

2.2 Treatment Protocol, the detailed treatment after IC should be described.

Figure 1 and 3, AUC of 0.58 is not so high. Why this value was chosen?

Line 123, Detailed explanation for Blood logistic Model should be necessary for readers' understanding. Were the parametars scored with cut-off?

Similarly, I would like to hear an explanation about making ROC curve of TNM in Figure 1(f).

Line 118, HDL-C, but HDL in Figure 1(b). They should be unified.

The limitation and advantage of this study should be added in Discussion part (limitation : retrospective analyses, advantage : same therapeutic group, etc.).

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

It is a relatively large series of advanced laryngeal squamous cell carcinomas.

The paper is written in an understandable yet improvable English, and a revision by a native English speaker would have helped.

The statistical work done on blood parameters and the nomogram built in order to assess the ability to predict response to IC is very interesting. Anyway, there are 2 orders of major issues concerning:

1.     The design:

a.     it is not clear how the patients were included in the IC versus surgery group in the beginning, are there internal guidelines? Was it based on patient preference? There are T4 cases in the IC group, which are not usually suitable of larynx preservation protocols according to main international guidelines.

b.     The IC treatment protocol is not clear at all: in fact in the abstract, it is written that the patients underwent total laryngectomy anyway after IC, which would be a nonsense according to the current guidelines, as confirmed by the fact, described in the abstract, that there are no differences in PFS and OS between IC and total laryngectomy group.

                                               i.     Secondary unclarity: in the abstract at the beginning of the results section an AUC is described in the IC group, but the endpoint considered is not defined (PFS, OS, response?)

2.     Interpretation of results:

a.     The clinical perspective of the study is not clear: are the predictor supposed to predict success of larynx preservation protocols? The larynx preservation protocols used (radiotherapy with or without SIB, with the addiction of chemotherapy, partial laryngea surgery?) are not described at all.

b.     Laryngeal preservation rates are not provided nor discussed. Also, disease specific survival is notoriously as important as OS in these studies, as it allows to verify whether larynx preservation protocols have an impact in mortality from other causes.

There is a clear lack of relevant citations concerning the clinical aspects of larynx preservation, starting from the fundamental randomized clinical trials which demonstrated the feasibility and potential of non-surgical laryngeal preservation (DOI: 10.1056/NEJMoa031317; DOI: DOI: 10.1056/NEJM199106133242402).

I would suggest also to mention the work of Italian groups which explored surgical and non-surgical laryngeal preservation in a real-world setting (doi: 10.1002/hed.22994; doi: 10.1002/hed.21785; doi: 10.1002/hed.21085).

Author Response

Please see the attachment.  The file has 8 pages.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

I congratulate the authors for their efforts to address the observed issues and clear improvements to the paper. Now the clinical perspective is clearer and the paper appears more coherent and interesting.

Yet, the English language and the phrasing can still be improved.

For example, looking at the introduction:

Line 51 and following: “local advanced” should be replaced with “locally advanced”.

Line 51 to 55: Total laryngectomy (TL), which reduces life quality (I would replace it with: quality of life), is often needed when dealing with the surgery (I would replace it with: when surgery is chosen as treatment modality)[3]. Induction chemotherapy (IC), administrated before surgery or  radiotherapy, is an alternative for advanced LSCC patients (I would replace it with: is an option to get information about radiosensitivity and chose the more appropriate treatment modality between surgery and radiotherapy)[4]. However, IC responses are heterogenetic (heterogeneous) in patients, and some patients don’t benefit from it [5]…..etc

Similar improvements in phrasing appear needed along the whole paper.

Also, always in the introduction, the 5-yr OS lower than 50% refers probably to the Chinese reality, but this figure is higher in other areas as US (where ACS data describe 5-yr OS of 66%), or Europe (5-OS between 50% and 70%). The authors should precise that the cited figure refers to China, and/or add the survival rates reported in other areas.

Author Response

Please see the attachment.

Author Response File: Author Response.docx