Radiation Segmentectomy for Hepatocellular Carcinoma

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Thank you for the opportunity to review this nicely written review of radiation segmentectomy (RADSEG) for the treatment of early-stage HCC.  The authors provide a comprehensive summary of the recent literature of HCC ablative therapies, highlighted outcomes of the various commonly used therapies in terms of pathologic, curative responses, and as a bridge to surgical therapies such as resection and transplantation.  The authors provide an in-depth discussion of the dosimetry of regional radiation therapy.

 

This review advances the field of ablative tumor therapy by summarizing data from recent studies and comparing various modalities.  As there are currently several regional therapies in use for the treatment of early-stage HCC, this review helps clarify the field to the reader in terms of modalities, mechanism, indications and outcomes.  Overall, it is well-written and well-referenced. 

 

Based on the presented data, could the authors propose reasonable guidelines for implementation of RADSEG, in terms of tumor size and location, dosages of therapy, patient selection and follow-up. For example, what they would wish to use at their institution. 

 

Please expand on the summary to better highlight, in a condensed fashion, the advantages and disadvantages of RADSEG such that the main takeaway points of the presented data are better appreciated in a summary version.  

 

Minor edits:

Pg 1, Ln 7 & 24; Yttrium spelled incorrectly.

Pg 3, Ln 82 & 97; parenthesis missing in the denominator.

Pg 3, Ln 85 & 94; define LSF and Tc-MAA.

 

Author Response

We are grateful for the reviewer’s comments and suggestions. These were helpful, allowing us to strengthen this manuscript. Individual reviewer comments are addressed below.

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Reviewer 1:

Thank you for the opportunity to review this nicely written review of radiation segmentectomy (RADSEG) for the treatment of early-stage HCC.  The authors provide a comprehensive summary of the recent literature of HCC ablative therapies, highlighted outcomes of the various commonly used therapies in terms of pathologic, curative responses, and as a bridge to surgical therapies such as resection and transplantation.  The authors provide an in-depth discussion of the dosimetry of regional radiation therapy.

This review advances the field of ablative tumor therapy by summarizing data from recent studies and comparing various modalities.  As there are currently several regional therapies in use for the treatment of early-stage HCC, this review helps clarify the field to the reader in terms of modalities, mechanism, indications and outcomes.  Overall, it is well-written and well-referenced. 

Based on the presented data, could the authors propose reasonable guidelines for implementation of RADSEG, in terms of tumor size and location, dosages of therapy, patient selection and follow-up. For example, what they would wish to use at their institution. 

R1.1. Included. Please see lines 206 → 219.

Please expand on the summary to better highlight, in a condensed fashion, the advantages and disadvantages of RADSEG such that the main takeaway points of the presented data are better appreciated in a summary version.  

R1.2. Included. Please see conclusion.

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for the opportunity to review Radiation Segmentectomy for HCC by Serhal et al. The article provides an excellent coverage and up-to-date review of RADSEG.  Please find minor comments on the review content below.

 

Ln. 107-108        Although defined in the prior lines, a slightly deeper description of what the R_T/N is reflecting would help and possibly further explanation of what variables are available to adjust to achieve a reduction in the D^N such as GBq activity at delivery.

The Complete pathologic necrosis (CPN) section is a good summary of some available literature on RADSEG and CPN. However, there are some major limitations in that literature that may be worth noting. Most often, the data is biased as those patients who were not effectively bridged or downstaged to surgery are obviously omitted, so the relationship between RADSEG (even above the dose thresholds) and CPN is biased to tumors responding to treatment. More importantly, we rarely know the dose distribution, 70^th percentile dose coverage (D70) for instance, and the number of treatment cycles prior to surgical intervention. While the target CPN outcomes reported for ⁹⁰Y are outstanding, there are some analytical/statistical weaknesses in the available data.

In the paragraph encompassing Ln 204 – 214, another important consideration for TARE is that it’s effectiveness as a bridge to transplant option is the dramatic improvements in target time to retreatment and target duration of response, specifically as related to TACE. The authors address this in the following section but would be important to acknowledge here.

Comments on the Quality of English Language

There are formatting and grammatical errors throughout, including:

Ln. 94    In the line “Tc-MAA as a surrogate for microsphere tumor”, some words appear to be missing. Tc-MAA as a surrogate for sphere distribution in the tumor.

Ln. 150  Specific gravity should be revised to specific activity.

Ln. 188 Treatment of solitary

Capitalization in the titles varies throughout the sub-sections.

Author Response

We are grateful for the reviewer’s comments and suggestions. These were helpful, allowing us to strengthen this manuscript. Individual reviewer comments are addressed below.

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Reviewer 2:

Thank you for the opportunity to review Radiation Segmentectomy for HCC by Serhal et al. The article provides an excellent coverage and up-to-date review of RADSEG.  Please find minor comments on the review content below.

Ln. 107-108        Although defined in the prior lines, a slightly deeper description of what the R_T/N is reflecting would help and possibly further explanation of what variables are available to adjust to achieve a reduction in the D^N such as GBq activity at delivery.

R2.1. Included.

The Complete pathologic necrosis (CPN) section is a good summary of some available literature on RADSEG and CPN. However, there are some major limitations in that literature that may be worth noting. Most often, the data is biased as those patients who were not effectively bridged or downstaged to surgery are obviously omitted, so the relationship between RADSEG (even above the dose thresholds) and CPN is biased to tumors responding to treatment. More importantly, we rarely know the dose distribution, 70^th percentile dose coverage (D70) for instance, and the number of treatment cycles prior to surgical intervention. While the target CPN outcomes reported for ⁹⁰Y are outstanding, there are some analytical/statistical weaknesses in the available data.

R2.2. We appreciate the reviewer's insightful comments on the limitations of the literature discussed in the CPN section. While acknowledging inherent biases, notably the exclusion of certain patient groups, our focus is to present a summary of outcomes reported in peer-reviewed publications. Limitations in radiology-pathology correlative studies (which is not limited to the radioembolization literature) are acknowledged but fall outside the purview of this review manuscript. We recognize the importance of future research addressing these limitations for a more comprehensive understanding of the relationship between RADSEG and CPN.

In the paragraph encompassing Ln 204 – 214, another important consideration for TARE is that it’s effectiveness as a bridge to transplant option is the dramatic improvements in target time to retreatment and target duration of response, specifically as related to TACE. The authors address this in the following section but would be important to acknowledge here.

R2.3. Included.