Classic Kaposi Sarcoma: Current Treatment Strategies and Emerging Therapeutic Approaches

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript addresses Classic Kaposi’s sarcoma (CKS), a rare and understudied vascular neoplasm associated with Kaposi’s sarcoma–associated herpesvirus. The topic is clinically relevant, particularly given the limited disease-specific guidance compared with HIV-associated Kaposi’s sarcoma. The authors aim to provide an overview of management strategies and emerging therapies, which is a worthwhile objective. However, in its current form, the manuscript suffers from substantial scientific, structural, formatting, and language deficiencies that significantly limit its clarity, rigor, and suitability for publication as a review article. Major revisions are required before the manuscript can be reconsidered.

Multiple paragraphs lack appropriate citations, see e.g. lines 36–46, where statements are presented without supporting references. This issue occurs throughout the manuscript and undermines its credibility as a review.

There is a consistent failure to introduce abbreviations correctly. For example: Kaposi sarcoma is mentioned for the first time around line 37, yet the abbreviation is introduced only later (line 49). HLA is used in line 62 without prior definition. This issue persists throughout the text.

The manuscript contains several layout and organizational errors that should have been addressed prior to submission: A “Results” section remains present (line 46), which is inappropriate for a review article and must be removed. Lines 51–53 list the four clinical forms of Kaposi sarcoma; however, this section requires careful editing to correct formatting and typographical errors. Overall, the manuscript does not currently conform to the expected structure of a review paper.

Numerous formatting issues detract from the manuscript’s professionalism:

• Gene names (e.g., BPTF at line 74) should be written in italics according to standard scientific conventions
• Lines 89–109 are poorly structured and read as disorganized notes rather than a coherent review paragraph; this section requires extensive rewriting
• P-values should be removed (line 251), as they are not appropriate in a narrative review context
• Bold formatting should be removed (line 286).

Figures and tables require substantial revision:

• Figure descriptions are insufficiently detailed and should better explain the content and relevance of each figure
• Lists of abbreviations should be included for clarity
• For Figure 2, the source of the images must be clearly stated, including permissions if applicable
• Table 1: the reference column should be clearly distinguished and consistently formatted
• Table 2 is incomplete  and must be fully revised to include all the studies, not only selected ones and finalized before resubmission

The section titled “Clinical Trials and Novel Therapies” represents the most important component of this review but is not sufficiently comprehensive or critical. The discussion lacks depth regarding: Ongoing or recent clinical trials specifically relevant to Classic Kaposi’s sarcoma, mechanistic rationale for emerging therapies, clear future perspectives and unmet clinical needs

Author Response

Multiple paragraphs lack appropriate citations, see e.g. lines 36–46, where statements are presented without supporting references. This issue occurs throughout the manuscript and undermines its credibility as a review.

We thank the reviewer this important comment The concern regarding missing citations has been thoroughly addressed. Supporting references have been added to the identified sections (e.g., lines 36-46), and the entire manuscript was systematically reviewed to ensure that all scientific statements are now supported by appropriate references. All necessary citations have been inserted where required to ensure the academic rigor and credibility of the review.

There is a consistent failure to introduce abbreviations correctly. For example: Kaposi sarcoma is mentioned for the first time around line 37, yet the abbreviation is introduced only later (line 49). HLA is used in line 62 without prior definition. This issue persists throughout the text.

We have carefully revised the manuscript to ensure that all abbreviations are introduced upon their first occurrence. Specifically, 'Kaposi sarcoma' is now defined with its abbreviation (KS) at the first mention, and terms such as HLA (Human Leukocyte Antigen) have been properly defined prior to use. The entire text was rechecked to ensure consistent abbreviation use throughout the manuscript. In addition, a comprehensive 'Abbreviations' section has been added to the manuscript to improve clarity and facilitate better understanding for the reader.

The manuscript contains several layout and organizational errors that should have been addressed prior to submission: A “Results” section remains present (line 46), which is inappropriate for a review article and must be removed. Lines 51–53 list the four clinical forms of Kaposi sarcoma; however, this section requires careful editing to correct formatting and typographical errors. Overall, the manuscript does not currently conform to the expected structure of a review paper.

We sincerely regret the organizational and formatting issues present in the original submission. The manuscript has now undergone substantial restructuring to conform to the expected format of a narrative review. Specifically:

• The 'Results' heading has been removed and replaced with 'Current Knowledge' to better suit the review format.
• The section describing the four clinical forms of Kaposi sarcoma (lines 51-53) has been carefully edited to correct typographical and formatting issues.
• The overall flow of the manuscript has been revised to ensure a logical transition between sections, including epidemiology, molecular pathogenesis, and therapeutic strategies.
  

  Numerous formatting issues detract from the manuscript’s professionalism:

  • Gene names (e.g., BPTF at line 74) should be written in italics according to standard scientific conventions
  • Lines 89–109 are poorly structured and read as disorganized notes rather than a coherent review paragraph; this section requires extensive rewriting
  • P-values should be removed (line 251), as they are not appropriate in a narrative review context
  • Bold formatting should be removed (line 286).

  We have addressed all formatting issues to to improve clarity and professionalism:

  • Gene Nomenclature: All gene names (e.g., BPTF, ORF73, K3/K5) are now formatted in italics in accordance with scientific conventions.
  • Section Restructuring: Lines 89-109 have been extensively rewritten and reorganized. The previously fragmented notes have been converted into a coherent narrative that explains KSHV pathogenesis and its impact on the human cell cycle and oncogenesis.
  • Statistical Data: As suggested, P-values have been removed (e.g., line 251) to maintain the appropriate style for a narrative review.
  • Text Formatting: Inappropriate bold formatting (e.g., line 286) has been removed to ensure a clean and professional presentation.

Figures and tables require substantial revision:

• Figure descriptions are insufficiently detailed and should better explain the content and relevance of each figure

Figure legends have been expanded and revised to provide clearer explanations of the figures and their relevance to the manuscript.

• Lists of abbreviations should be included for clarity

In accordance with the reviewer’s suggestion, a comprehensive 'Abbreviations' section has been added to the manuscript to improve clarity and facilitate reader comprehension.

 

• Table 1: the reference column should be clearly distinguished and consistently formatted

Table 1 has been revised to ensure that the 'References' column is clearly distinguished and consistently formatted. The citation style has been standardized, and table alignment has been improved for better readability and presentation.

Table 2 is incomplete and must be fully revised to include all the studies, not only selected ones and finalized before resubmission

To address partially conflicting suggestions from different reviewers, we retained the table summarizing selected key trials and added an additional paragraph discussing future prospects in KS research.

 

Reviewer 2 Report

Comments and Suggestions for Authors

This manuscript provides a narrative review of classic Kaposi’s sarcoma (CKS), with emphasis on therapeutic strategies and emerging treatments. The review is generally well-referenced. However, revisions are required. The main issues relate to structure, clarity, redundancy and critical synthesis.

I have the following comments:

-The manuscript is descriptive, summarizing available studies without sufficient critical judgment. The authors should more clearly compare therapies (e.g., PLD vs paclitaxel, immunotherapy vs antiangiogenic agents), discuss strengths, limitations, and quality of evidence (case series vs trials) and clarify where evidence is extrapolated from HIV-associated KS and where data are truly CKS-specific. Please add short paragraphs at the end of major sections stating what should be preferred in practice and what remains experimental.

-Several sections are overly long (e.g., epidemiology/genetics, systemic therapy). Also there is repetition of concepts (e.g., rarity of CKS, lack of trials, extrapolation from HIV-KS). Headings such as “Results” are not appropriate for a narrative review. Please replace “Results” with “Current Knowledge” or something similar. Condense genetic/immunologic details to what is clinically relevant and improve transitions between sections to guide the reader.

-Table 1 lacks clarity and uniform formatting (e.g., inconsistent ORR values, missing toxicity comparisons). Some dosing schedules are excessive for a review and belong in guidelines rather than summary tables. The footnote stating “All approved therapies are class 2a recommendation” is confusing. Please simplify Table 1 to focus on line of therapy, ORR range, key toxicities. Clearly specify whether recommendations are NCCN, ESMO, or expert opinion.

-Grammatical errors, typos, and awkward phrasing remain despite the AI-assisted language check. Examples include incorrect verb tenses, inconsistent capitalization, and unclear sentences (e.g., line 317 “initial response was have been reported”). A professional language edit is required.

-Some statements are too strong given the level of evidence (e.g., “impressive response rates” for small phase II immunotherapy trials).

-The “Future perspective” section could be shortened and focused on most promising strategies, rather than listing trials.

 

Comments on the Quality of English Language

Grammatical errors, typos, and awkward phrasing remain despite the AI-assisted language check. Examples include incorrect verb tenses, inconsistent capitalization, and unclear sentences (e.g., line 317 “initial response was have been reported”). A professional language edit is required.

Author Response

-The manuscript is descriptive, summarizing available studies without sufficient critical judgment. The authors should more clearly compare therapies (e.g., PLD vs paclitaxel, immunotherapy vs antiangiogenic agents), discuss strengths, limitations, and quality of evidence (case series vs trials) and clarify where evidence is extrapolated from HIV-associated KS and where data are truly CKS-specific. Please add short paragraphs at the end of major sections stating what should be preferred in practice and what remains experimental.

We thank the reviewer for the careful and constructive evaluation. We have integrated sentences comparing the different therapies (e.g., PLD vs. Paclitaxel, immunotherapy vs. antiangiogenic agents) and clarified the distinction between evidence extrapolated from HIV-associated KS versus CKS-specific data.

In addition, brief concluding paragraphs were added at the end of major sections to distinguish current standard-of-care approaches from experimental therapies.

-Several sections are overly long (e.g., epidemiology/genetics, systemic therapy). Also there is repetition of concepts (e.g., rarity of CKS, lack of trials, extrapolation from HIV-KS). Headings such as “Results” are not appropriate for a narrative review. Please replace “Results” with “Current Knowledge” or something similar. Condense genetic/immunologic details to what is clinically relevant and improve transitions between sections to guide the reader.

This issue has been addressed throughout the manuscript.

Sections were condensed to reduce redundancy, particularly regarding the rarity of CKS, the lack of clinical trials, and the extrapolation from HIV-KS literature.

As suggested, the “Results” heading was replaced with “Current Knowledge.” Genetic and immunologic discussions were streamlined to focus on clinically relevant information, and transitions between sections were improved to enhance readability.

-Table 1 lacks clarity and uniform formatting (e.g., inconsistent ORR values, missing toxicity comparisons). Some dosing schedules are excessive for a review and belong in guidelines rather than summary tables. The footnote stating “All approved therapies are class 2a recommendation” is confusing. Please simplify Table 1 to focus on line of therapy, ORR range, key toxicities. Clearly specify whether recommendations are NCCN, ESMO, or expert opinion.
Table 1 has been revised to improve clarity and readability.

-Grammatical errors, typos, and awkward phrasing remain despite the AI-assisted language check. Examples include incorrect verb tenses, inconsistent capitalization, and unclear sentences (e.g., line 317 “initial response was have been reported”). A professional language edit is required.
Regarding the language and phrasing:

The manuscript has undergone comprehensive language editing, with corrections to grammar, verb tense, capitalization, and sentence structure throughout the text.

-Some statements are too strong given the level of evidence (e.g., “impressive response rates” for small phase II immunotherapy trials).

Addressed in text.

 

-The “Future perspective” section could be shortened and focused on most promising strategies, rather than listing trials.

Because reviewers provided differing recommendations regarding the scope of this section, we retained the discussion but improved its clarity and organization to better highlight the most promising research directions. 

 

 

 

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Authors of the manuscript mostly addressed my queries. Minor issues are mostly editorial. 

Author Response

Authors of the manuscript mostly addressed my queries. Minor issues are mostly editorial
We thank the reviewer for their careful reading of the revised manuscript and for their positive feedback regarding our previous responses

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript was significantly improved.

Author Response

The manuscript was significantly improved.
We thank the reviewer for their careful reading of the revised manuscript and for their positive feedback regarding our previous responses