Fractionated Stereotactic Radiation for Central Nervous System Lymphoma: Retrospective Analysis of Initial Cases
Round 1
Reviewer 1 Report
SCI level academic papers cannot be written and published in such a concise manner. In the Method section, please describe at least the treatment method for your institution in more detail, including targeting. I think you should refer to other published papers. Listing the stories of 10 patients has limited academic significance. If the authors want to publish a paper based on that treatment experience, they should at least know what they learned and what they want to say from your treatment experience. Therefore, authors must provide a meaningful clinical question at the end of the introduction and provide an answer to that question in the conclusion. The authors provide neither the hypothesis questions nor the conclusions of the current study. Descriptive revision is not available at this stage.Author Response
Thank you for your review. Please see our responses below
“In the Method section, please describe at least the treatment method for your institution in more detail, including targeting. I think you should refer to other published papers.”
- We have elaborated on our planning, targeting, and treatment procedures in the Methods section. We have included a reference for our radical dose WBRT treatment from prior CNS lymphoma study. We have also elaborated on the rationale for fractionated SRS in the introduction section
“ If the authors want to publish a paper based on that treatment experience, they should at least know what they learned and what they want to say from your treatment experience. Therefore, authors must provide a meaningful clinical question at the end of the introduction and provide an answer to that question in the conclusion”
- We have reorganized our introduction and discussion to include a specific clinical question that is answered in the discussion – namely, is fSRS a reasonable treatment option to be explored in patients with CNS lymphoma who decline WBRT or are unfit for WBRT? We have also added a conclusion to this effect
Reviewer 2 Report
The authors present a paper about "Fractionated stereotactic radiation for central nervous system lymphoma: retrospective analysis of initial cases".
The topic is interesting however the results could be improved.
In table 1 for example "Time to local recurrence" is missing in most cases as well as "Time from fSRS to last follow-up if living".
I appreciate the details of the ten cases presented however I beleive that the atuhors should reorganize the paper trying to provide a summary of their findings which could be clinically meaningful.
Also the introduction and the discussion sections are too short and should be expanded; I believe that a conclusion should be added.
Author Response
Thank you for your review. Please see our responses below
“In table 1 for example "Time to local recurrence" is missing in most cases as well as "Time from fSRS to last follow-up if living".”
- In these cases, an entry of “N/A” has been added to cases where this column is irrelevant. For instance, as only two patients were alive at last follow up, all but two patients have “N/A” for “time from fSRS to last follow-up, if living”.
“I believe that the authors should reorganize the paper trying to provide a summary of their findings which could be clinically meaningful.”
- A table summarizing each case has been included, along with a summary of clinically meaningful findings such as incidence of local and distant recurrence, time to recurrence, median survival
“Also the introduction and the discussion sections are too short and should be expanded; I believe that a conclusion should be added.”
- The introduction and discussion sections have been expanded with further references to relevant studies to provide further rationale and context. A conclusion has been added
Reviewer 3 Report
Dear uthors,the series of cases presented is very heterogeneous as it includes 4 cases of distant brain metastases whose management has nothing to do with primary CNS lymphomas and which is highly influenced by the management of systemic disease, so I do not think they should be included in the study.
Currently, the management of primary CNS lymphomas is done with holocranial radiotherapy using low doses when long-term toxicity is to be avoided or with chemotherapy schemes that pass the blood-brain barrier. An approach such as the one presented to us should be done under clinical trial (NCCCN guidelines CNS primary lymphoma V1 2023).
It is very important that in more recent cases, use the RTOG's recursive parctitioning analysis (RPA) assessment, which does not appear in the text.
The bibliography is very old and outdated, and there are several articles from the 2020s on this subject.
Author Response
Thank you for your review. Please see our responses below.
“The series of cases presented is very heterogeneous as it includes 4 cases of distant brain metastases whose management has nothing to do with primary CNS lymphomas and which is highly influenced by the management of systemic disease, so I do not think they should be included in the study. “
- We appreciate that the patient population in this study is heterogeneous, and have provided direct acknowledgement of the particular cases that do not represent primary CNS lymphoma. However, we feel that there is still useful information obtained by presenting these cases, as the protocol at our centre is to treat brain-only relapse of systemic lymphoma similarly to the treatment of primary CNS lymphoma. This rationale and context has been added to the materials and methods section
“Currently, the management of primary CNS lymphomas is done with holocranial radiotherapy using low doses when long-term toxicity is to be avoided or with chemotherapy schemes that pass the blood-brain barrier. An approach such as the one presented to us should be done under clinical trial (NCCCN guidelines CNS primary lymphoma V1 2023).”
- We thank the reviewer for this comment, and appreciate that our treatment outlined in this study is not supported by randomized prospective evidence. We have been careful in this report to provide our rationale for treatment only in specific contexts when whole brain radiation is declined or would not be tolerated. We have also been diligent in expressing that this is an exploratory treatment option that may provide rationale for further study in this context.
“It is very important that in more recent cases, use the RTOG's recursive parctitioning analysis (RPA) assessment, which does not appear in the text. “
- The RPA was based on RTOG trials investigating brain metastases from solid tumours, with histologies listed as squamous, adenocarcinoma, small cell, large cell, non-small cell, or melanoma, and only 4% of their histologies “unknown” or “other”, per Gaspar et al. (1997). Thus we do not think it is relevant for inclusion in this study that deals exclusively with lymphoma.
“The bibliography is very old and outdated, and there are several articles from the 2020s on this subject.”
- We have updated our bibliography to include more relevant trials involving brain radiation for CNS lymphoma, including long-term analysis of PRECIS from 2022 and the abstract to RTOG 1114 from 2020.
Reviewer 4 Report
Overall I thought this was an interesting case report. I only have a few comments.
In the introduction lines 32-33, the authors cite minimal side effects of SRS and then say fSRS is considered a promising technique. Why were these patients treated with fSRS instead of SRS? I assume it’s because the target volume was larger than traditionally used for SRS, but that should be stated and any references given.
For Table 1, the caption says “This is a table…” and that should be replaced with a real caption.
The whole-brain dose is higher than used for traditional WBRT (30 Gy in 10 fx is standard to balance the toxicity with efficacy). Why is 37.5 Gy in 15 fx used here, and why is it higher for some patients (45 Gy in 25 fx for case 5, 20 Gy in 5 fx for case 8)? References should be provided for guidance to appropriate WBRT dose in case of failure after fSRS.
Author Response
Thank you for your review. Please see our responses below
“In the introduction lines 32-33, the authors cite minimal side effects of SRS and then say fSRS is considered a promising technique. Why were these patients treated with fSRS instead of SRS? I assume it’s because the target volume was larger than traditionally used for SRS, but that should be stated and any references given.”
- We have added further rationale to the use of fSRS in the introduction, including the high alpha/beta ratio of lymphoma and the large tumour volume
For Table 1, the caption says “This is a table…” and that should be replaced with a real caption.
- We thank the reviewer for this comment – the table caption has been replaced
The whole-brain dose is higher than used for traditional WBRT (30 Gy in 10 fx is standard to balance the toxicity with efficacy). Why is 37.5 Gy in 15 fx used here, and why is it higher for some patients (45 Gy in 25 fx for case 5, 20 Gy in 5 fx for case 8)? References should be provided for guidance to appropriate WBRT dose in case of failure after fSRS.
- We have provided further rationale for our WBRT dosing in our materials and methods section along with supporting reference
Round 2
Reviewer 1 Report
The manuscript has much improved after the revision
Reviewer 2 Report
The manuscript has much improved after the revision
Reviewer 3 Report
Dear author, your contributions are enriching of the previous version, I consider that your contribution can be useful in selected cases such as those included in the article.
