PTEN R130Q Papillary Tumor of the Pineal Region (PTPR) with Chromosome 10 Loss Successfully Treated with Everolimus: A Case Report

Round 1

Reviewer 1 Report

Review for manuscript entitled “PTEN R130Q Papillary Tumor of the Pineal Region (PTPR) with 2 Chromosome 10 Loss Successfully Treated with Everolimus: A 3 Case Report.”

This study evaluates a case of recurrent intracranial anaplastic PTPR characterized by a 72 PTEN R130Q alteration with chromosome 10 loss that was treated with everolimus alone after surgical excision and radiotherapy. 

The study is well formulated and the attractive aspect of this study is that it promotes the use of everolimus as a noninvasive and safe therapeutic intervention. Although the results look encouraging, I would suggest adding a sentence or two in the discussion part that future studies with a large sample size are needed for validation of the therapeutic effects. Probably preclinical studies can be a valid approach as well.

This case study is impressive however that being said there remains a need to add further details about the mechanism of everolimus therapy. I mean how it works on the gene pathway and the exact pathophysiology.

In addition,  are there any details about the long term prognosis of the reported case? If yes, I think it will beneficial to add such information in terms of prognosis in the long run.

In general, the case report is worth publishing after the very minor changes I suggested. I believe that it can of significance in paving the way towards using such therapeutic intervention. 

Author Response

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Reviewer 2 Report

The authors describe a single case of a PTPR patient who showed a reduction of the tumor mass during the targeted therapy with everolimus on the off-lable use base. This is an interesting observation regarding the lack of sufficient systemic treatment options in this tumor entity.

Nevertheless, the clinical course of this patient may be summarized in a more precisely focused manner. Moreover, previously published data regarding molecular findings in PTPR cases and series should be summarized more detailed at the introduction part. Without further molecular and histological validation work-up, the scientific content and novelty seems to be too low to be considered for publication at the current form. The authors should e.g. perform further histological confirmation tests of the mTOR pathway in the corresponding tumor tissue and thus confirm the functional significance of the genomic finding in this single case.

Moreover, previously published data regarding molecular findings in PTPR cases and series should be summarized more detailed at the introduction part.

Author Response

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Round 2

Reviewer 2 Report

I appreciate, the authors have updated the manuscript intensively and answered most questions appropriately. Nevertheless, some questions still remain open. The immunohistochemical validation is still missing. The genomic findings are typical for the tumor entity and this is actually not the first case describing the potential effectiveness of Everolimus in this tumor entity. The additional benefit for the scientific world is very limited in my opinion.

The introduction regardiing molecular pathways and single molecular players became too long for a single case report at the current version.

Moreover, the treatment is stated as monotherapy with Everolimus. At the same time Figure 3 and text passages describe surgery and radiation treatment in the period of Everolimus treatment. This Figure and the lines 160-170 of the manuscript are not consistent to me. Why the treatment with radiation and surgery were performed at a regredient tumor lesion? This should be commented in detail and the conclusions should be adapted to this facts.

Author Response

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