Proton Radiotherapy for Vestibular Schwannomas in Patients with NF2-Related Schwannomatosis: A Case Series
, Kimberley S. Koetsier 1, Victor S. van Dam 2, Scott R. Plotkin 3, Frederick G. Barker 4, D. Bradley Welling 5, Jeroen C. Jansen 1, Erik F. Hensen 1 and Helen A. Shih 6
Round 1
Reviewer 1 Report
Please see file attached
Comments for author File: 
Comments.docx
Author Response
Please see the attachment.
Author Response File: Author Response.docx
Reviewer 2 Report
The authors should be commended for their interesting study on this important topic. Despite the very low cohort size (n=8), this study adds some important information regarding the use of proton-therapy for treating vestibular schwannomas in NF2 patients.
Please find following my comments:
1) Methods: The authors should explicitly report how they made the diagnosis of VS in case of lesions not biopsied/surgically treated. If they only used imaging (i.e., MRI) diagnosis, they should report this limitation and they should also mention the radiological criteria used to make such diagnoses and differentiate them from other skull base tumors (e.g., meningiomas).
2) Methods: "At our center, radiotherapy is not the first option of choice for NF2 patients. In most 94 cases, treatment with bevacizumab will be attempted first to control tumor progression 95 and preserve hearing. If bevacizumab fails or is not well tolerated, surgery is considered 96 generally before radiation therapy." Does this apply to all patients? Even for those with large lesions and severe debilitating symptoms? The authors should clarify if surgery or RT/PRT is indeed never a "first-line" option in NF2 patients or if there are some exceptions to such rule.
3) Methods: "Proton radiotherapy was deliv- 101 ered with a cyclotron-based passive scattering system. The prescribed dose was 50.4 to 54 102 Gy(relative biological effectiveness: RBE) in 28 or 30 fractions, or 12 Gy(RBE) in proton 103 SRS." Is this a protocol approved by one of the international RT societies or is it a protocol uniquely devised/approved at the authors' institution? Please clarify.
4) Methods: "Tumor 108 dimensions were assessed in cubic centimeters (cm3) derived from Magnetic Resonance 109 Imaging (MRI)." Did the author measure the tumor dimensions before and after PRT or only before? If such dimensions were measured after PRT, did the author consider and account for any treatment-related radiological effect (e.g., radiation necrosis or responsive edema) that may have affected the lesion size? Please clarify.
5) Results: The authors report the indications for PRT and the other therapies each patient has received. However, they do not report how many lesions were treated in each patient with each therapy (e.g., "surgery performed on both sides in X patients") and how many lesions (not patients) received PRT after previous therapies. Please clarify.
6) Results/Discussion: The authors should clarify how they were able to differentiate PRT-related toxicity effects and response effects from outcomes related to any additional therapy administered before or after PRT.
Author Response
Please see the attachment.
Author Response File: Author Response.docx
Reviewer 3 Report
Limitations are well stated.
Author Response
We thank the reviewer for his/her time and careful consideration. No comments required revision.
