Boron Neutron Capture Therapy: Clinical Application and Research Progress

Round 1

Reviewer 1 Report

Line 27_-Should say- Malignant tumors are a serious threat to human life..

 

Line 28- Delete according to different types of radiation and instead say- There are many different modalities of radiation therapy including…

Line 32- Should say- The potential for BNCT use in various disease sites such as breast and prostate cancer, and the improved efficacy of many novel boron delivery agents, are currently being extensively investigated in preclinical settings.

Line 34- With additional studies, BNCT has the potential to become a major means of anti-tumor therapy.

 

 

Line 36- BNCT is not necessarily new, so can take that word out

Line 38- say- The basic principle is that a boron-containing drug is injected into the patient, the boron compound accumulates in the tumor cells, and the tumor area is then irradiated with a neutron beam

Line 41-say- 10B, it transforms into 11B and the unstable 11B decays rapidly and emits α particles (4He), and recoil atoms 7Li (including ground state and excited 42 state in a fission reaction.

Line 65- say - BNCT requires that boron-containing drugs selectively deliver

Line 98- For safety reasons, the construction site of the 98 facility is usually limited- can you elaborate a little bit on this?

 

Line 323- Say- The standard treatment regimen for newly diagnosed GM is maximum tumor resection, plus concurrent temozolomide chemoradiotherapy followed by temozolomide adjuvant chemotherapy

 

Line 384- Make this a complete sentence, it is a fragment currently: Age distribution: 48-86 years old, all were carcinoma in situ located on the sole or face

Line 388- say- No regional lymph node involvement, distant metastasis, or second malignancy were observed in any patients

Line 398- say- There are a large number of important organs sensitive to radiation in the head and neck region

Line 399- BNCT can target and kill cancer tissues while causing less damage to normal tissues. It is an ideal solution for radiation therapy of head and neck cancer – These two sentences are little simplistic, BNCT can potentially spare more normal tissues due to its biologically targeted nature, so you can say that, but I would not say its an ideal solution for H&N cancer. Please reword if possible

 

Line 434- Although the neutron reaction cross section of boron is much larger than that of other elements in the table, but as the main elements constituting the human body, their quantity in tissues is a factor that cannot be ignored.- this sentence is very confusing, please reword to make your point more clear

These tiles should be pleural- Second/third generation boron delivery agents

Section 6- Particularity of BNCT- Maybe this section should be renamed as “Additional considerations when utilizing BNCT”, as it combines a number of different topics including neutron properties, BNCT side effects. Should also probably include a few sentences on BNCT dosimetry and treatment planning.

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 2 Report

This is an excellent and very contributory review of clinical BNCT studies. It will be very useful to scientists and clinicians interested in BNCT. It also presents views on the future of BNCT that are very contributory.

I think the manuscript is worthy of publication once the authors have addressed the following issues:

1) I suggest the authors change the title to a more "inclusive" title. I think the present title uderestimates the content of the manuscript.

2) Introduction, line 31: the authors should briefly mention the "established pathologies" for BNCT. 

3) Line 78, section Neutron beams: clarify what you mean by "deep tumors in vitro"

4) Page 3, at the top. The list of accelerator facilities is incomplete. The authors should either complete the list or state that the facilities they mention are examples...

5) Page 3, line 129, "intracavity guide" - please include a reference if available.  

6) Page 3, line 145: non-targeting instead of none-targeting. 

7) Page 4, line 152: "four different boron compounds" - please say which compounds.

8) Page 4, line 177: Finland conducted instead of conducts (FiR-1 is no longer available).

9) Page 7, lines 223-225: please explain mechanisms.

10) Page 8, lines 247-248: Please explain the phrase "During BNCT....venous blood" 

11) Page 8, lines 261 and 262: please use the same end-point to compare. 

12) Page 9: line 318: In what order are the therapies applied? Based on what working hypothesis? 

13) Page 10, lines 333-336. Please mention toxicity findings.

14) Page 10, line 357: dose instead of duration?

15) Page 10, line 369: "BNCT is only suitable for superficial tumors" - clarify in what conditions. Deep-seated tumors can also be treated. 

16) Page 12, line 445: "Fractionated irradiation can directly reduce the dose to normal tissue" - please clarify. Fractionated irradiation gives normal tissue an advantage in terms of repair capacity vs tumor...or allows for boron re targeting of tumor populations that were refractory to the first application...or do you mean the use of different irradiation fields? 

17) Page 13 line 490 - please explain why

18) Page 13, line 498: which clinical trials have been conducted with third-generation boron delivery agents? 

19) Please mention if in your view there is a need for randomized clinical trials.

20) Please stress the need for research in animal models for the advancement of BNCT. 

 

 

 

Author Response

Please see the attachment

Author Response File: Author Response.docx