Sensorineural Hearing Loss as the Prominent Symptom in Meningeal Carcinomatosis

Round 1

Reviewer 1 Report

It is an interesting paper reporting sensorineural loss as the prominent symptom in meningeal carcinomatosis. 

The numbers of patients studied are confusing. The abstract mentions 8 patients with meningeal carcinomatosis (MC) and sensorineural hearing loss from the authors's institution and 35 patients identified through a review of the literature. Those 35 patients are not mentioned in the introduction part. In the Materials and Methods section, the authors mention 42 patients with MC from their own institution including 8 patients with sensorineural hearing loss. All this should be made clear in the text throughout the manuscript.

In the Results section, when mentioning age of onset, the authors should clearly state what they are referring to (age at onset of cancer? of meningeal carcinomatosis? of hearing loss?). 

The authors retrieved 35 additional patients from the literature but the corresponding paragraph (3.5) in the manuscript is very short. The authors should develop this part. 

Would detecting MC at an early stage change the prognosis of the disease given the small efficacy of current treatments? 

Page 3, line 120: what are the other CSF tests with normal results?

What is pharmacotherapy compared to chemotherapy? (abstract and page 4, line 144).

English needs editing.

Author Response

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Reviewer 2 Report

The authors summarized the clinical data of 8 meningeal carcinomatosis (MC) patients with sensorineural hearing loss (SNHL) and 35 patients reported from publications. This is an interesting research regarding SNHL in MC patients. However, there are lot of issues that should be reworked.

Major issues:

1. In this study, glioma patients are included in 42 MC cases. They are not exactly MC cases. These data might be removed from the analysis. Otherwise, previous glioma cases reported from publications should also be included in this systematic review.
2. In Table1, types of primary tumors in each group should be clarified. Moreover, the results and Table1 should include data regarding impaired consciousness and epileptic or non-epileptic convulsions.
3. The authors state that the symptoms of hearing loss were improved after therapy in 4 (50%) patients (focal radio therapy and pharmacotherapy for 3 patients and whole brain radiotherapy for 1 patient) for the 8 patients with SNHL. Readers probably want to know which cases have improved. So, the 8 MC patients with SNHL shown in Table 2 should also be listed in Table 3 including treatment for MC and patient outcome as well as age, gender, side of SNHL and primary tumor, in the same order. This information is important for citations in future papers.
4. The authors state that gadolinium-enhanced MRI revealed that the thickening and enhancement of both vestibulocochlear nerves in 4 (50%) patients. Representative MRI in cases with MC with and without SNHL should be added.

Minor issues:

1. In Table1, a part of calculation in percentage is incorrect. That should be reworked.
2. The authors state that all procedures were approved by the ethics committee of their institution. Please provide the approval number.

Author Response

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Reviewer 3 Report

The authors retrospectively report on 8 patients (from a single-institution cohort of 42) with SNHL as part of their disease course from LMD. Strengths of this study include a larger cohort of uniformly diagnosed patients (+ CSF cytology). Further, the report is interesting and merits dissemination. There are several issues that should be addressed prior to publication:

1. At least twice in the manuscript (introduction and results), the authors state that MC has a "broad spectrum of clinical manifestations in [the] nervous system, involving cerebrum, cerebellum..Symptoms don't involve anatomic regions of the brain. They can be referred to involvement of these structure, but these sentences don't make sense in the fact that you get symptoms (or clinical manifestations) FROM involvement of these structures.
2. Results: the authors need to be consistent about the values obtained from the CSF. For instance, all values (including CSF pressure) should have a median and a range. 
3. In the paragraph discussing demographics of all patients, should mention systemic disease states is you can. Also would be helpful to have PFS and OS of all patients (as well as SHNL patients) and if they died of neurologic involvement or from systemic disease progression.
4. Section 3.3, last line of second paragraph "others CSF tests exhibited..." We don't know what other tests there were - so please remove this sentence. 
5. Table 3 does not add anything to the manuscript. I would strike this table.  A table outlining the demographics of all 8 patients with SNHL would be much more helpful and should be considered in place of the current table.
6. Lastly, the manuscript requires extensive editing for English language

Author Response

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Round 2

Reviewer 2 Report

The manuscript has been revised well excepting 3rd suggestion. The 8 MC patients with SNHL should be listed in Table 3 (after Nakashima's case, as 'the present cases') including treatment for MC and patient outcome as well as age, gender, side of SNHL and primary tumor, in the same order. If these data are included in Table 3, the added information (age, gender, side of SNHL and primary tumor) in Table 2 should be deleted. This information is important for citations in future papers. 

Author Response

Please see the attachment.

Author Response File: Author Response.docx