The Impact of Nanomedicine on Soft Tissue Sarcoma Treated by Radiotherapy and/or Hyperthermia: A Review

Round 1

Reviewer 1 Report

The authors provide an interesting and generally well written review on the use of nanoparticles during radiotherapy, chemotherapy and hyperthermia for soft tissue sarcoma. Some comments are to be made.

The authors should stress in the Introduction that the use of nanoparticles in radiotherapy, chemotherapy and hyperthermia concerns preoperative treatment or treatment of unresectable tumours, when the tumour is still in situ, and not as adjuvant treatment. Therefore, the indications for preoperative radiotherapy and preoperative chemotherapy in soft tissue sarcoma should be discussed. Hence, the advantages of preoperative instead of postoperative radiotherapy should be discussed, with referral to the randomized trial of O’Sullivan (O’Sullivan et al., Lancet 2002; Davis et al., J Clin Oncol 2002; Davis et al., Radiother Oncol 2005). Please discuss these issues.

The authors should mention the adverse events (injection-site pain, hypotension and postoperative scar necrosis) with the use of NBTXR3 to improve preoperative radiotherapy effect in soft tissue sarcoma of extremities and trunk wall in the studies of Bonvalot et al. (ref. 25 and 26). In these studies, the nanoparticles were injected in the tumour. In case of retroperitoneal sarcomas which are usually very large in size when diagnosed, its potential application seems to be limited.

The authors note that soft tissue sarcomas are radio-resistant, but myxoid liposarcoma is extremely radio-sensitive. Therefore, in the phase 2/3 trial of Bonvalot et al. randomization was stratified according to myxoid liposarcoma vs. other histological subtypes and results were accordingly analyzed. Please discuss these issues.

Moreover, the way of administration, intravenously vs. intratumourly, should be discussed.

 The manuscript should be reviewed for editing errors. Examples are the following. Spaces in the sentences are often too abundantly used, especially before the dot at the end of a sentence, and at other sites lacking. ‘nps’ should be written consistently as ‘NPs’ through the entire text. After firstly explain the acronym STS, soft tissue sarcoma should be referred to as STS in the following text. Similarly, the acronym FISS for fibrosarcoma is firstly mentioned in the discussion, whereas the term fibrosarcoma is mentioned multiple times previously.

Finally, as this topic concerns preoperative treatment instead of adjuvant treatment and specific as part of a multimodality approach to soft tissue sarcomas, I would suggest to submit the manuscript not to the special issue of ‘Adjuvant Therapy in Cancer’ but to the, more specific, special issue of ‘Multimodality Management of Sarcoma

Some improvement of editing is encouraged.

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Reviewer 2 Report

Dear Editor, The review  explore  the potential application of nanoparticles in Radio- 2 therapy and/or Hyperthermia treatment for Soft Tissue Sarcomas (STS).  Although the aim is to analyze and compare the current body of literature some points need to be better commented

-  In my opinion, novel perspectives on the use of nanoparticles are very shortly commented and need further improve. 

An additional chapter on which are the main problems of individual types of nanoparticle and how they can be addressed

 Appropriate identification of the chapter for example if 3.3.0 title  is liposome and radiotherapy 3.3.1 couldn't be  magnetic  nanoparticle but an additional chapter on liposome please added doi: 10.3390/cells12172204.

 Dear Editor, The review  explore  the potential application of nanoparticles in Radio- 2 therapy and/or Hyperthermia treatment for Soft Tissue Sarcomas (STS).  Although the aim is to analyze and compare the current body of literature some points need to be better commented

-  In my opinion, novel perspectives on the use of nanoparticles are very shortly commented and need further improve. 

An additional chapter on which are the main problems of individual types of nanoparticle and how they can be addressed

 Appropriate identification of the chapter for example if 3.3.0 title  is liposome and  radiotherapy 3.3.1 couldn't be  magnetic  nanoparticle but an additional chapter on liposome please added doi: 10.3390/cells12172204.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

 Dear Editor,

the authors  revised  the manuscript  answering all my points

I agree to the publication

Dear Editor,

the authors  revised  the manuscript  answering all my points

I agree to the publication