Locoregional Hyperthermia in Cancer Treatment: A Narrative Review with Updates and Perspectives

Round 1

Reviewer 1 Report (Previous Reviewer 1)

Comments and Suggestions for Authors

It’s a very interesting article,practically a current and complete picture of HT and what it represents today.At the same time,it’s difficult to navigate the text due to the multitude of studies and their results for many neoplastic localizations.The paper presents the significant studies on HT and this work is remarkable.i find redundant the method used to double the text with supplementary tables that practically present the same informations as the text that precedes.For clarity,maybe a sentence should be added at the end of each neoplastic localization to emphasize the HT method used and the elective indication.Disscusions are balanced and present both the important data from literature regarding the good results obtain for the association of HT with different oncological treatments but also the objective and subjective causes that have prevented the standardization of HT in cancer treatment.Practically there are all data available today  to establish the current place of HT.The conclusions are well structured  and to the point.The Refferences are well chosen and correctly cited.The English language is fluent.

Author Response

Comments and Suggestions for Authors

Author's Reply to the Review Report (Reviewer 1)

It’s a very interesting article,practically a current and complete picture of HT and what it represents today. At the same time,it’s difficult to navigate the text due to the multitude of studies and their results for many neoplastic localizations.

The paper presents the significant studies on HT and this work is remarkable.i find redundant the method used to double the text with supplementary tables that practically present the same informations as the text that precedes.

Author response: Dear reviewer, thank you for this suggestion, but the reviewer who preceded you had asked to insert tables for greater clarity and we did it

For clarity,maybe a sentence should be added at the end of each neoplastic localization to emphasize the HT method used and the elective indication.

Author response: we inserted the HT method in the materials and methods: all the studies were performed with devices for radiative hyperthermia, the studies that used other devices are specified and report the method as: mEHT in cervical and pancreatic tumors and ultrasound hyperthermia in head and neck tumors.

Disscusions are balanced and present both the important data from literature regarding the good results obtain for the association of HT with different oncological treatments but also the objective and subjective causes that have prevented the standardization of HT in cancer treatment. Practically there are all data available today  to establish the current place of HT.The conclusions are well structured  and to the point.

The Refferences are well chosen and correctly cited.The English language is fluent.

Author response: thank you very much for your appreciation

Reviewer 2 Report (Previous Reviewer 3)

Comments and Suggestions for Authors

The reviewer is pleased to see the revision by the authors by including “manuscript from 2020 to 2025 to avoid repetition of our previous review”. 
Since this review focuses on locoregional hyperthermia (RHT), the reviewer would not recommend the inclusion of whole-body hyperthermia (WBH) in this review. 
Would the author consider hyperthermic intraperitoneal chemotherapy (HIPEC) as a form of Locoregional Hyperthermia?
Looking forward to seeing your work at ICHO 2025 in Seoul

Author Response

Author's Reply to the Review Report (Reviewer 2)

The reviewer is pleased to see the revision by the authors by including “manuscript from 2020 to 2025 to avoid repetition of our previous review”. 
Since this review focuses on locoregional hyperthermia (RHT), the reviewer would not recommend the inclusion of whole-body hyperthermia (WBH) in this review. 

Author response: even if whole body hyperthermia is not a method referable to Regional hyperthermia we wanted to include this information for further clarification and completeness as there are many interested doctors who frequently ask about it in conferences dedicated to hyperthermia

Would the author consider hyperthermic intraperitoneal chemotherapy (HIPEC) as a form of Locoregional Hyperthermia?

Author response: even if HIPEC uses hyperthermia it remains a method exclusively of the surgical branch and is not the competence of radiation oncologists or medical oncologists so we have not considered it for this review

Looking forward to seeing your work at ICHO 2025 in Seoul

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This is a very interesting article about the place and role of hyterthermia(HT) în oncology.it’s a generos topic and the work put into eelecting useful articles and synthesizing important and current data for so manyocations of cancer must be appreciated.It’s an Up-to-date X-ray of what HT nowadays means in oncology.The Simple Summary and the Abstract are well designed and clear about the authors intentions.The introdu ction is clear and presents the basics about HT in oncology.Materials and Methods chapter is very succint(a short sentence) and  it would require some additional explanations.The Results represent the main pillar of the article,presenting the la test and most important data about HT in the different neoplastic localizations.The presentation of the data is very clear and fluent.There is also a typing error in the Malignancies of the head and neck-the mention of Burns’study is about 3 years no monthes.The data are comprehensive and widely presented ,generally with favorable results.Discussions is a to short chapter and should also include the problem of limited diffusion of the HT from Conclusions.Really concusions are only the first and the last sentences from  conclusions chapter.The Discussions and Conclusions chapters need to be reelaborated.The English language uzed is fluent and references are numeros correctly chosen and well cited.

Reviewer 2 Report

Comments and Suggestions for Authors

This review examines the role of regional hyperthermia (HT) in oncology, highlighting its documented benefits in cancer control, tumor regression, and survival improvement. Despite strong clinical evidence, HT remains underutilized due to limited guidelines, outdated technology, and lack of acceptance among oncologists. HT enhances chemotherapy, radiotherapy, and immunotherapy by increasing tumor temperature (39–43°C), promoting immune response, and facilitating DNA damage in cancer cells. Recent studies suggest HT may improve treatment outcomes by modulating the tumor microenvironment. However, here are some comments to authors.

1. It lacks a description of the method and relevant medical devices used to perform HT in the section of Materials and Methods.
2. It would be better if a detailed discussion on temperature monitoring technology is included in the article.
3. For better readability, please tabulate each tumor type, treatment method and significant outsome, such as overall survival. 

Reviewer 3 Report

Comments and Suggestions for Authors

I would consider recommendations for publication if the authors can focus solely on the latest development since 2019, rather than since 2010. Similar topics have been covered extensively in numerous reviews, including the ones by the authors. 
In this article:
“Only articles written in English referring to well-reported observational, phase II and prospective III studies, systematic reviews, and meta-analyses were considered, which were published mainly between 2010 and 2025.”
In the author’s previous review:
•    Fiorentini, G., Sarti, D., Gadaleta, C. D., Ballerini, M., Fiorentini, C., Garfagno, T., ... & Guadagni, S. (2020). A narrative review of regional hyperthermia: updates from 2010 to 2019. Integrative cancer therapies, 19, 1534735420932648.
“This review aims to update the current knowledge on HT use in association with RT and/or CHT from 2010 up to 2019.”