How Arterial Embolization Is Transforming Treatment of Oncologic and Degenerative Musculoskeletal Disease

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Thank you to the authors for addressing this current and complex topic.

Abstract
The abstract would benefit from restructuring. To enhance clarity and readability, consider dividing it into specific sections: "Background," "Materials and Methods," "Discussion," and "Conclusions."

Introduction

• Lines 34, 38, and 67: Please include references.
• TACE is used as an acronym but should be introduced in full text before abbreviation.
• Several parts lack clarity and may appear fragmented.

Central Section
This section is well-organized and engaging, with a thorough and meticulous description of all treatments.

Discussion

• The authors should enhance this section by emphasizing the study’s strengths.
• What are the disadvantages, side effects, and contraindications?
• Lastly, under which clinical scenarios is oncological embolization the preferred option?

Author Response

Responses to the reviewer's comments

We would like to thank Reviewers for taking the time to review the manuscript. We sincerely appreciate all valuable comments and suggestions, which helped us to improve the quality of the manuscript. We provide one copy of the revised manuscript with the changes highlighted by the “Track Changes” function.

 

Reviewer #1

 

Abstract
1. The abstract would benefit from restructuring. To enhance clarity and readability, consider dividing it into specific sections: "Background," "Materials and Methods," "Discussion," and "Conclusions."

Response: Thank you for this suggestion, we have restructured the abstract accordingly.

Introduction

2. Lines 34, 38, and 67: Please include references.

Response: According to the Reviewer’s suggestion, we have provided relevant references

3. TACE is used as an acronym but should be introduced in full text before abbreviation.
   Response: According to the Reviewer’s suggestion, we have provided the full text of the acronym

Several parts lack clarity and may appear fragmented.

Central Section
This section is well-organized and engaging, with a thorough and meticulous description of all treatments.

Discussion

4. The authors should enhance this section by emphasizing the study’s strengths.
   Response: According to the Reviewer’s suggestion, we have added the sentences “. This review thoroughly compiles and discusses the literature on these topics, summarizing the main findings in tables when many articles are available. Selected case studies are presented throughout the review to enhance the reader’s experience.” in the discussion.

 

5. 5. What are the disadvantages, side effects, and contraindications?

Response: We thank the Reviewer for the useful comment, we clarified these concepts by adding the following text in the discussion: “Limited side effects have been reported in the literature. In oncologic embolization, post-embolization syndrome—defined as fever, nausea and vomiting, and increased ischemic pain—has been observed in roughly 20% of patients, although it is self-limiting within one week after the procedure [6]. For degenerative embolization, side effects appear to be less common and less severe, probably due to the reduced aggressiveness of the embolization itself and the limited ischemic effect. Skin discoloration is the most common side effect, affecting 12.5% of patients [16].
Arterial embolization has certain disadvantages and contraindications. Disadvantages include the risk of non-target embolization leading to unintended tissue damage, radiation exposure during the procedure, and the potential for symptom recurrence necessitating repeat interventions [25, 30-36]. Contraindications encompass patients with severe atherosclerotic disease limiting catheter access, uncorrectable coagulopathy or bleeding disorders, severe renal insufficiency that precludes the use of contrast agents, and hypersensitivity to embolic materials or contrast media [30-36].”

 

6. 6. Lastly, under which clinical scenarios is oncological embolization the preferred option?

Response: Thank you for this very pertinent comment. According to the Reviewer’s suggestion, we have clarified this concept through the text by adding the sentences “The preferred clinical scenarios for oncologic embolization vary according to the type of lesion. For bone metastases, large, lytic, hypervascular lesions that do not respond to radiotherapy or chemotherapy are ideal candidates for embolization to achieve pain reduction and local disease control [6-8]. For primary bone tumors, the indication is usually related to the location of the lesion, where proximity to neurovascular structures often makes percutaneous or surgical approaches less effective [99-101]” in the discussion. We have also added an additional table that summarizes clinical setting and indications (Table 4).

 

 

Clinical Setting	Indication	Primary Goals	Key Points
Oncologic	Hypervascular bone metastases (e.g., renal cell carcinoma, thyroid)	Pain palliation, local control	Effective for pain relief and reducing intraoperative blood loss; ideal for hypervascular metastases unresponsive to radio/chemotherapy.
	Primary bone tumors (e.g., aneurysmal bone cysts, desmoid fibromatosis)	Alternative to surgery or percutaneous ablations	Useful when tumors are near neurovascular structures, offering symptom control with minimal invasiveness.
Preoperative	Tumors requiring surgical resection in difficult-to-access areas (e.g., pelvis, spine)	Reduce blood loss during surgery	Reduces perioperative complications and enhances tumor visualization for surgical intervention.
Palliative	Advanced malignancies with limited curative options	Symptom relief	Suitable for patients with poor surgical candidacy, providing temporary symptom relief and improved quality of life.
Degenerative	Knee osteoarthritis, adhesive capsulitis	Pain reduction, functional improvement	Expands options for patients unresponsive to conservative treatments but not candidates for surgery.
Inflammatory Musculoskeletal	Conditions like lateral epicondylitis, chronic tendinopathy	Pain relief, functional recovery	Offers symptom management in chronic inflammatory cases where conservative management has failed.

 

 

Reviewer #2

1) I disagree the authors include degenerative disease in this review because the journal's target should be "Oncology." 

2. 2. Giant cell tumor:  The authors should add the role of denosumab for the treatment of unresectable GCT. I think denosumab may play a critical role in the treatment of unresectable GCT now.

Response: We have clarified this concept through the text by adding the sentence “Denosumab is often used to control this tumor, however its use is still disputed due to the reported increased risk of recurrence in case of curettage and of the increased risk of malignant transformation in the long term [Li H, Gao J, Gao Y, Lin N, Zheng M, Ye Z. Denosumab in Giant Cell Tumor of Bone: Current Status and Pitfalls. Front Oncol. 2020 Oct 2;10:580605. doi: 10.3389/fonc.2020.580605. PMID: 33123484; PMCID: PMC7567019.]” in the TCG section.

3. 3. Desmoid tumor: Please add the role of pazopanib. 

Response: we clarified the concept by adding “[87,92], including Pazopanib [Toulmonde M, Pulido M, Ray-Coquard I, Andre T, Isambert N, Chevreau C, Penel N, Bompas E, Saada E, Bertucci F, Lebbe C, Le Cesne A, Soulie P, Piperno-Neumann S, Sweet S, Cecchi F, Hembrough T, Bellera C, Kind M, Crombe A, Lucchesi C, Le Loarer F, Blay JY, Italiano A. Pazopanib or methotrexate-vinblastine combination chemotherapy in adult patients with progressive desmoid tumours (DESMOPAZ): a non-comparative, randomised, open-label, multicentre, phase 2 study. Lancet Oncol. 2019 Sep;20(9):1263-1272. doi: 10.1016/S1470-2045(19)30276-1. Epub 2019 Jul 19. PMID: 31331699.],” in the desmoid section.

4. Haemangioma: Please add the role of embolization for soft tissue haemangioma.

Response: Thank you for the very useful comment, according to the Reviewer’s suggestion, we have added the following text “The literature on the embolization of soft tissue hemangiomas is limited compared to that on bone hemangiomas. Embolization may be useful in high-flow soft tissue hemangiomas, where it can help manage symptoms and reduce lesion size by decreasing blood flow to the tumor [Lamanna A, Maingard J, Florescu G, Kok HK, Ranatunga D, Barras C, Lee MJ, Brooks DM, Jhamb A, Chandra RV, Asadi H. Endovascular balloon-assisted liquid embolization of soft tissue vascular malformations: technical feasibility and safety. CVIR Endovasc. 2021 Jun 8;4(1):49. doi: 10.1186/s42155-021-00236-4. PMID: 34101056; PMCID: PMC8187498.]. A study by Mavrogenis et al. [Mavrogenis AF, Rossi G, Calabrò T, Altimari G, Rimondi E, Ruggieri P. The role of embolization for hemangiomas. Musculoskelet Surg. 2012 Aug;96(2):125-35. doi: 10.1007/s12306-012-0207-2. Epub 2012 Jun 9. PMID: 22684541.] retrospectively reviewed 31 patients treated for painful bone and soft tissue hemangiomas with embolization. For soft tissue hemangiomas specifically, the procedure provided complete pain relief in 10 out of 16 patients, with recurrences in a subset that were successfully managed with repeat embolizations.

Reviewer 2 Report

Comments and Suggestions for Authors

The review described the role of arterial embolization in the Orthopaedic field.

1) I disagree the authors include degenerative disease in this review because the journal's target should be "Oncology." 

2) Giant cell tumor:  The authors should add the role of denosumab for the treatment of unresectable GCT. I think denosumab may play a critical role in the treatment of unresectable GCT now.

3) desmoid tumor: Please add the role of pazopanib. 

4) Haemangioma: Please add the role of embolization for soft tissue haemangioma.

Author Response

Responses to the reviewer's comments

 

We would like to thank Reviewers for taking the time to review the manuscript. We sincerely appreciate all valuable comments and suggestions, which helped us to improve the quality of the manuscript. We provide one copy of the revised manuscript with the changes highlighted by the “Track Changes” function.

Reviewer #2

1) I disagree the authors include degenerative disease in this review because the journal's target should be "Oncology." 

2. 2. Giant cell tumor:  The authors should add the role of denosumab for the treatment of unresectable GCT. I think denosumab may play a critical role in the treatment of unresectable GCT now.

Response: We have clarified this concept through the text by adding the sentence “Denosumab is often used to control this tumor, however its use is still disputed due to the reported increased risk of recurrence in case of curettage and of the increased risk of malignant transformation in the long term [Li H, Gao J, Gao Y, Lin N, Zheng M, Ye Z. Denosumab in Giant Cell Tumor of Bone: Current Status and Pitfalls. Front Oncol. 2020 Oct 2;10:580605. doi: 10.3389/fonc.2020.580605. PMID: 33123484; PMCID: PMC7567019.]” in the TCG section.

3. 3. Desmoid tumor: Please add the role of pazopanib. 

Response: we clarified the concept by adding “[87,92], including Pazopanib [Toulmonde M, Pulido M, Ray-Coquard I, Andre T, Isambert N, Chevreau C, Penel N, Bompas E, Saada E, Bertucci F, Lebbe C, Le Cesne A, Soulie P, Piperno-Neumann S, Sweet S, Cecchi F, Hembrough T, Bellera C, Kind M, Crombe A, Lucchesi C, Le Loarer F, Blay JY, Italiano A. Pazopanib or methotrexate-vinblastine combination chemotherapy in adult patients with progressive desmoid tumours (DESMOPAZ): a non-comparative, randomised, open-label, multicentre, phase 2 study. Lancet Oncol. 2019 Sep;20(9):1263-1272. doi: 10.1016/S1470-2045(19)30276-1. Epub 2019 Jul 19. PMID: 31331699.],” in the desmoid section.

4. Haemangioma: Please add the role of embolization for soft tissue haemangioma.

Response: Thank you for the very useful comment, according to the Reviewer’s suggestion, we have added the following text “The literature on the embolization of soft tissue hemangiomas is limited compared to that on bone hemangiomas. Embolization may be useful in high-flow soft tissue hemangiomas, where it can help manage symptoms and reduce lesion size by decreasing blood flow to the tumor [Lamanna A, Maingard J, Florescu G, Kok HK, Ranatunga D, Barras C, Lee MJ, Brooks DM, Jhamb A, Chandra RV, Asadi H. Endovascular balloon-assisted liquid embolization of soft tissue vascular malformations: technical feasibility and safety. CVIR Endovasc. 2021 Jun 8;4(1):49. doi: 10.1186/s42155-021-00236-4. PMID: 34101056; PMCID: PMC8187498.]. A study by Mavrogenis et al. [Mavrogenis AF, Rossi G, Calabrò T, Altimari G, Rimondi E, Ruggieri P. The role of embolization for hemangiomas. Musculoskelet Surg. 2012 Aug;96(2):125-35. doi: 10.1007/s12306-012-0207-2. Epub 2012 Jun 9. PMID: 22684541.] retrospectively reviewed 31 patients treated for painful bone and soft tissue hemangiomas with embolization. For soft tissue hemangiomas specifically, the procedure provided complete pain relief in 10 out of 16 patients, with recurrences in a subset that were successfully managed with repeat embolizations.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Thank you to the authors for accepting suggestions. The responses to the comments are highly relevant

Author Response

Thank you for your feedback.

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for submitting the revision.

I don't agree with the strategy of giant cell tumor. Please see the review of Jpn J Clin Oncol 2022 May 5;52(5):411-416.doi: 10.1093/jjco/hyac018.  They recommend denosmab for unresectable GCT after the era of denosmab.

 

 

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 3

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for your comments. I appreciate your revision.

Comments on the Quality of English Language

No comments.