Survival Difference in Advanced-Stage Cervical and Ovarian Cancer Patients Treated with Concomitant Modulated Electro-Hyperthermia in Comparison to Classic Treatment Modalities: Results of a Pilot Study and Meta-Analysis

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript presents a timely pilot study and meta-analysis evaluating modulated electro-hyperthermia as an adjunct treatment in advanced cervical and ovarian cancer, combining institutional data with published evidence. The analysis suggests a potential survival benefit, particularly in cervical cancer, with acceptable safety. Overall, the work is clearly written and methodologically sound, but several areas require clarification to strengthen transparency and interpretability.

In the introduction, the rationale would benefit from a clearer distinction between biological plausibility and clinical evidence, explicitly acknowledging ongoing controversy and uncertainty around mEHT to better frame the study’s exploratory nature.

In the materials and methods, the handling of heterogeneity between the retrospective pilot cohort and published studies should be described in more detail, particularly how differences in prior treatments and disease stage were accounted for. In addition, the meta-analysis methods should clarify whether and how shared control groups or overlapping populations across studies were assessed and managed to avoid double counting.

In the results, greater clarity is needed on the contribution of the single-institution pilot data to the pooled estimates, ideally with a brief sensitivity analysis or explicit statement of its influence. The reporting of heterogeneity would also benefit from more explicit interpretation, as the high I² values are presented numerically but not sufficiently contextualised.

In the discussion, the conclusions regarding survival benefit in cervical cancer should be more cautiously framed in light of the predominance of non-randomised data and high heterogeneity. Finally, the discussion should more explicitly address the clinical implications and limitations for ovarian cancer, emphasising that the absence of comparator groups precludes firm conclusions about effectiveness rather than implying equivalence or benefit.

Author Response

Budapest, February 5, 2026.

 

Dear Reviewer,

On behalf of our fellow Authors, first of all, we would like to thank you for your attention and opinion on our original article entitled “Survival difference of advanced-stage cervical and ovarian cancer patients treated with concomitant modulated electro-hyperthermia in comparison to classic treatment modalities: results of a pilot study and meta-analysis”. Here we provide answers to the comments the Reviewer raised.

 

The manuscript presents a timely pilot study and meta-analysis evaluating modulated electro-hyperthermia as an adjunct treatment in advanced cervical and ovarian cancer, combining institutional data with published evidence. The analysis suggests a potential survival benefit, particularly in cervical cancer, with acceptable safety. Overall, the work is clearly written and methodologically sound, but several areas require clarification to strengthen transparency and interpretability.

We thank the Reviewer for their kind words, that our manuscript is sufficiently detailed, and that they believe it is suitable to be published in the journal of Medical Sciences.

 

In the introduction, the rationale would benefit from a clearer distinction between biological plausibility and clinical evidence, explicitly acknowledging ongoing controversy and uncertainty around mEHT to better frame the study’s exploratory nature.

We thank the Reviewer for their kind criticism and agree with it. The introduction of the manuscript was extended to reflect a better understanding of the current uncertainties around mEHT. Furthermore, the exploratory nature of our study was also further highlighted. Please see lines 63-68 and 76-84 in the revised manuscript.

 

In the materials and methods, the handling of heterogeneity between the retrospective pilot cohort and published studies should be described in more detail, particularly how differences in prior treatments and disease stage were accounted for. In addition, the meta-analysis methods should clarify whether and how shared control groups or overlapping populations across studies were assessed and managed to avoid double counting.

We thank the Reviewer for their suggestions. Although none of the influence analyses showed any bias, based on the reports received for our initial submission we decided to remove our own institutional data from the meta-analysis part of the study. We agree with the opinion of all our Reviewers that the studies included in the meta-analysis and our own results make the meta-analysis too heterogeneous. Our results can be interpreted more likely as a case series rather than an observational study, moreover, the sample size is also extremely low compared to other studies. Therefore, leaving out these 3 and 4 patient results from the meta-analysis makes the remaining model more robust, although the number of studies and patients that can be included still remains a bit small.

Regarding the question on overlapping populations, the only possible overlap could be coming from including the two studies of Lee et al. (2017 and 2023). We carefully re-analyzed the two articles and confirmed that the two studies could not have overlapping populations. In the 2017 article Lee et al. applied mEHT in patients treated with chemotherapy, while in the 2023 study chemoradiotherapy was administered alongside with mEHT. The following was added to Chapter 3.2: “The two studies of Lee et al. [22,24] was carefully investigated whether there is an overlapping population. It was found that in the 2017 study they investigated mEHT alongside chemotherapy [25], while in the 2023 study chemoradiotherapy was administered for all of the patients [23].”

 

In the results, greater clarity is needed on the contribution of the single-institution pilot data to the pooled estimates, ideally with a brief sensitivity analysis or explicit statement of its influence. The reporting of heterogeneity would also benefit from more explicit interpretation, as the high I² values are presented numerically but not sufficiently contextualised.

We thank the Reviewer for their suggestions. As discussed in the previous question, our institutional data was ultimately removed from the meta-analysis part of the study.

 

In the discussion, the conclusions regarding survival benefit in cervical cancer should be more cautiously framed in light of the predominance of non-randomised data and high heterogeneity. Finally, the discussion should more explicitly address the clinical implications and limitations for ovarian cancer, emphasising that the absence of comparator groups precludes firm conclusions about effectiveness rather than implying equivalence or benefit.

Thank you. All these great suggestions had been implemented into the Discussion.

 

Yours sincerely,

Dr. A. Marcell Szasz and Dr. Zoltan Herold

Semmelweis University

Reviewer 2 Report

Comments and Suggestions for Authors

While the topic of Modulated Electro-Hyperthermia (mEHT) is of clinical interest, this manuscript presents a critical methodological error that compromises the validity of its statistical conclusions. My primary concern is the inclusion of the authors' own small, uncontrolled pilot data directly into the meta-analysis calculations:
The manuscript currently combines a small, single-institute pilot study with a broader meta-analysis in a manner that presents significant methodological concerns. While reporting both study types in one paper is permissible, mathematically integrating the authors' own unpublished pilot data directly into the meta-analysis forest plots (Figures 3A–F) introduces a critical "self-inclusion" bias. A meta-analysis is intended to be an objective synthesis of existing, peer-reviewed literature. By including fresh, unvetted data that has not yet passed independent peer review as a standalone dataset, the analysis risks circular validation—effectively "grading its own homework." If the pilot data contains any selection or technical flaws, these errors are propagated into the pooled effect sizes, compromising the validity of the entire meta-analysis.
Furthermore, the statistical integration of these two datasets creates an extreme imbalance in the level of evidence. In the cervical cancer analysis (Figure 3A), the model combines a large, high-quality Phase III Randomized Controlled Trial (Minnaar et al., 2022) with the authors' retrospective case series of only three patients. This introduces significant statistical noise without adding meaningful power, akin to diluting a rigorous dataset with anecdotal evidence. The issue is even more pronounced in the ovarian cancer section (Figure 3E), where the authors' pilot study of four patients constitutes nearly one-third (32.7%) of the statistical weight in a total pool of only 35 patients. Consequently, this section functions more as a "pooled case series" rather than a robust meta-analysis, and labeling it as the latter may mislead readers regarding the strength of the evidence.
To preserve the scientific integrity of both analyses, it is strongly recommended that the authors separate the two distinct datasets: 
The pilot study should be presented as a descriptive case series or a hypothesis-generating component. The meta-analysis should be conducted exclusively on previously published, peer-reviewed literature. The authors can then discuss their pilot results in the context of the meta-analysis (e.g., in the Discussion section) to highlight consistencies or discrepancies, rather than mathematically merging them. This approach would clarify the distinction between the new empirical data and the systematic review of established evidence.

Here are a few other major concerns and suggestions for the authors:
1.    Lack of Technical Reproducibility in the Pilot Study
The description of the mEHT treatment protocol in the pilot study currently lacks sufficient detail to allow for replication or adequate technical assessment. Specifically, the manuscript mentions a "step-up phase" for power but fails to define the specific protocol (e.g., initial wattage, time intervals, and wattage increments). Furthermore, the size of the electrode used (e.g., 20 cm vs. 30 cm) is not specified; given that appropriate electrode selection is critical for effective depth penetration in pelvic malignancies, this detail is mandatory. The authors must also clarify the coupling method used. Additionally, the description of the standard of care is too broad; for the ovarian cancer cohort, it is essential to specify whether patients were platinum-sensitive or platinum-resistant, and for the cervical cohort, the specific radiation dosages (EBRT and Brachytherapy) must be reported to interpret the survival data accurately.
2.    Insufficient Standardization of Safety Reporting
The reporting of adverse events in the pilot study is currently anecdotal and lacks standardized quantification. Describing side effects merely as "minor" or reporting a "burning sensation" without a reference to a validated grading system prevents objective safety evaluation. The authors should re-evaluate their safety data using the NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0) to assign specific grades to these events. Furthermore, given the known physics of RF-based hyperthermia, the manuscript should explicitly report whether checks for subcutaneous adipose burns were performed, rather than focusing solely on surface skin toxicity.
3.    Unaccounted Confounding Factors and Selection Bias
The baseline characteristics provided in Table 1 are incomplete regarding prognostic factors that significantly influence survival. Most notably, the ECOG Performance Status is missing; without knowing if the pilot cohort consisted of fit (ECOG 0-1) or debilitated (ECOG 3-4) patients, the survival outcomes cannot be contextualized. Additionally, the text notes that some cervical cancer patients "refused" chemotherapy. This classifies them as a non-compliant sub-population with distinct prognostic risks compared to the clinical trial populations cited in the meta-analysis. These confounding factors must be explicitly addressed as limitations, as they undermine the comparability of the cohorts.
4.    Discrepancies Between Results and Conclusions
There are instances where the conclusions drawn in the manuscript are not fully supported by the presented results. Specifically, the conclusion states that the efficacy "trend is similar in the case of ovarian tumors" to that of cervical cancer. However, the Results section explicitly acknowledges that due to a lack of control patients, no statistical comparisons were performed for the ovarian group. It is scientifically invalid to claim a comparative "trend" of efficacy in the absence of a control arm. Furthermore, the claim of a "~20% higher 2-year survival rate" in cervical cancer should be tempered by acknowledging the high statistical heterogeneity (I^2 > 90%) observed in the analysis, which suggests that the pooled estimate may not be essentially robust.

Author Response

Budapest, February 5, 2026.

 

Dear Reviewer,

On behalf of our fellow Authors, first of all, we would like to thank you for your attention and opinion on our original article entitled “Survival difference of advanced-stage cervical and ovarian cancer patients treated with concomitant modulated electro-hyperthermia in comparison to classic treatment modalities: results of a pilot study and meta-analysis”. Here we provide answers to the comments our Reviewer raised.

 

While the topic of Modulated Electro-Hyperthermia (mEHT) is of clinical interest, this manuscript presents a critical methodological error that compromises the validity of its statistical conclusions. My primary concern is the inclusion of the authors' own small, uncontrolled pilot data directly into the meta-analysis calculations:

The manuscript currently combines a small, single-institute pilot study with a broader meta-analysis in a manner that presents significant methodological concerns. While reporting both study types in one paper is permissible, mathematically integrating the authors' own unpublished pilot data directly into the meta-analysis forest plots (Figures 3A–F) introduces a critical "self-inclusion" bias. A meta-analysis is intended to be an objective synthesis of existing, peer-reviewed literature. By including fresh, unvetted data that has not yet passed independent peer review as a standalone dataset, the analysis risks circular validation—effectively "grading its own homework." If the pilot data contains any selection or technical flaws, these errors are propagated into the pooled effect sizes, compromising the validity of the entire meta-analysis.

Furthermore, the statistical integration of these two datasets creates an extreme imbalance in the level of evidence. In the cervical cancer analysis (Figure 3A), the model combines a large, high-quality Phase III Randomized Controlled Trial (Minnaar et al., 2022) with the authors' retrospective case series of only three patients. This introduces significant statistical noise without adding meaningful power, akin to diluting a rigorous dataset with anecdotal evidence. The issue is even more pronounced in the ovarian cancer section (Figure 3E), where the authors' pilot study of four patients constitutes nearly one-third (32.7%) of the statistical weight in a total pool of only 35 patients. Consequently, this section functions more as a "pooled case series" rather than a robust meta-analysis, and labeling it as the latter may mislead readers regarding the strength of the evidence.

To preserve the scientific integrity of both analyses, it is strongly recommended that the authors separate the two distinct datasets:

The pilot study should be presented as a descriptive case series or a hypothesis-generating component. The meta-analysis should be conducted exclusively on previously published, peer-reviewed literature. The authors can then discuss their pilot results in the context of the meta-analysis (e.g., in the Discussion section) to highlight consistencies or discrepancies, rather than mathematically merging them. This approach would clarify the distinction between the new empirical data and the systematic review of established evidence.

First, we would like to thank the Reviewer for their kind words and hard work on providing us with a very detailed report, which helped us a lot improving the manuscript. Furthermore, we thank the Reviewer that they believe it is suitable to be published in the journal of Medical Sciences.

We thank the Reviewer for their kind criticism regarding the inclusion of the case series data into the meta-analysis results. The Reviewer is completely wright that our results can be interpreted more likely as a case series rather than an observational study, moreover, the sample size is also extremely low compared to other studies. In light of these, all case series data was removed from the meta-analysis. Except for the 1-year survival rate data of cervical cancer decreasing somewhat, the meta-analysis result following the removal of our own institutional data basically remained the same, within a ±5% difference, compared to the original version of the manuscript. Please see the modified Results and Abstract for further details.

 

Here are a few other major concerns and suggestions for the authors:

1. Lack of Technical Reproducibility in the Pilot Study: The description of the mEHT treatment protocol in the pilot study currently lacks sufficient detail to allow for replication or adequate technical assessment. Specifically, the manuscript mentions a "step-up phase" for power but fails to define the specific protocol (e.g., initial wattage, time intervals, and wattage increments). Furthermore, the size of the electrode used (e.g., 20 cm vs. 30 cm) is not specified; given that appropriate electrode selection is critical for effective depth penetration in pelvic malignancies, this detail is mandatory. The authors must also clarify the coupling method used. Additionally, the description of the standard of care is too broad; for the ovarian cancer cohort, it is essential to specify whether patients were platinum-sensitive or platinum-resistant, and for the cervical cohort, the specific radiation dosages (EBRT and Brachytherapy) must be reported to interpret the survival data accurately.

We thank the reviewer for their kind criticism. The missing information on mEHT treatment was provided, including the detailed description of the step-up-phase, electrode size, etc. Please see the updated Chapter 2.2.

Regarding the question of oncological therapies, all the available details on the various chemotherapies the patients received were incorporated into Chapter 3.1. Unfortunately, the details of the irradiation – which only a single patient received – could not be found in our medical system, as this treatment was provided for the patient in another institute. In the available documentation we could only find that the patient received 4 cycles of irradiation with concomitant cisplatin chemotherapy.

2. Insufficient Standardization of Safety Reporting: The reporting of adverse events in the pilot study is currently anecdotal and lacks standardized quantification. Describing side effects merely as "minor" or reporting a "burning sensation" without a reference to a validated grading system prevents objective safety evaluation. The authors should re-evaluate their safety data using the NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0) to assign specific grades to these events. Furthermore, given the known physics of RF-based hyperthermia, the manuscript should explicitly report whether checks for subcutaneous adipose burns were performed, rather than focusing solely on surface skin toxicity.

We thank the Reviewer for their suggestion. The adverse effects were re-evaluated based on the latest version of CTCAE (v6.0). As the burning sensation, which is very typical for mEHT, was not specifically included in the latest CTCAE version (nor in the previous ones), we chose the closest definition to properly describe it. Please see the updated Chapter 3.1.

Specific measurement on subcutaneous adipose changes was not feasible, therefore, any signs for subcutaneous adipose burns were checked during the patients’ routine imaging studies (ultrasound, MRI or CT), where previous occurrences could be detected. Subcutaneous adipose burn was never observed for any of the patients included in our case series.

The Methods and Limitations sections were updated accordingly.

 

3. Unaccounted Confounding Factors and Selection Bias: The baseline characteristics provided in Table 1 are incomplete regarding prognostic factors that significantly influence survival. Most notably, the ECOG Performance Status is missing; without knowing if the pilot cohort consisted of fit (ECOG 0-1) or debilitated (ECOG 3-4) patients, the survival outcomes cannot be contextualized. Additionally, the text notes that some cervical cancer patients "refused" chemotherapy. This classifies them as a non-compliant sub-population with distinct prognostic risks compared to the clinical trial populations cited in the meta-analysis. These confounding factors must be explicitly addressed as limitations, as they undermine the comparability of the cohorts.

We thank the Reviewer for their recommendations how to further extend and edit our manuscript. ECOG performance score higher than 1 was an exclusion criterion of the study. We confirm and sorry that the exclusion criteria of the pilot study was missing in the original submission. Methods was extended with the following: “Exclusion criteria included < 18 years of age, previous and/or synchronous other malignancy, active-phase autoimmune disease or an active infection, mental illnesses, and a > 1 Eastern Cooperative Oncology Group (ECOG) performance score.”

The details on every oncological treatment the patients received prior mEHT were updated significantly. We could also clarify that there was actually only a single patient who refused some of the oncological treatments, including chemotherapy. We fully agree with the Reviewer that the presentation of such patient(s) is not ideal, as their treatment carries a much higher risk than that of those who accepted chemotherapy earlier. However, we note that unfortunately we still encounter such cases often in the daily oncological practice. For this reason, and due to the already extremely low number of cases, we would not consider excluding this patient from the case series section. We have supplemented the limitations with the text suggested by the Reviewer.

 

4. Discrepancies Between Results and Conclusions: There are instances where the conclusions drawn in the manuscript are not fully supported by the presented results. Specifically, the conclusion states that the efficacy "trend is similar in the case of ovarian tumors" to that of cervical cancer. However, the Results section explicitly acknowledges that due to a lack of control patients, no statistical comparisons were performed for the ovarian group. It is scientifically invalid to claim a comparative "trend" of efficacy in the absence of a control arm. Furthermore, the claim of a "~20% higher 2-year survival rate" in cervical cancer should be tempered by acknowledging the high statistical heterogeneity (I^2 > 90%) observed in the analysis, which suggests that the pooled estimate may not be essentially robust.

We thank the Reviewer for pointing out these inaccuracies / wording issues in the Discussion. We have revised the text to be more clear and refined the sometimes-exaggerated wordings.

 

Yours sincerely,

Dr. A. Marcell Szasz and Dr. Zoltan Herold

Semmelweis University

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Thank you for your revision

Author Response

Budapest, February 11, 2026.

 

Dear Reviewer,

 

On behalf of our fellow Authors, first of all, we would like to thank you for your attention and opinion on our original article entitled “Survival difference of advanced-stage cervical and ovarian cancer patients treated with concomitant modulated electro-hyperthermia in comparison to classic treatment modalities: results of a pilot study and meta-analysis”. Here we provide answers to the comments the Reviewer raised.

 

Thank you for your revision.

We thank the Reviewer for their kind words and that they believe it is suitable to be accepted in the journal of Medical Sciences.

 

Yours sincerely,

Dr. A. Marcell Szasz and Dr. Zoltan Herold

Semmelweis University

Reviewer 2 Report

Comments and Suggestions for Authors

While they successfully fixed the descriptive and technical flaws (e.g., adding device settings and safety grading), they completely rejected the primary methodological recommendation to separate their pilot data from the meta-analysis. The authors cleaned up the reporting quality (better descriptions, standardized safety metrics) but ignored the scientific validity concern (statistical weight of their own data). By refusing to decouple the pilot study from the meta-analysis, the manuscript still contains the "fatal flaw" identified in the initial review.

The reviewer’s strongest recommendation was to remove the authors' own pilot data from the meta-analysis calculations to avoid "circular validation." In the revised abstract and methods, the authors explicitly state: "The results of our institutional pilot study were incorporated into the meta-analysis" and "In addition, the results presented in the observational part of the current study were also included in the meta-analysis". The "Ovarian Cancer" meta-analysis is still methodologically compromised, as it continues to weight their small, uncontrolled pilot study against published literature.

The reviewer noted missing ECOG scores and the issue of including patients who "refused" standard care. They added that "all patients had an ECOG performance score of 0", which clarifies the baseline health of the cohort. They kept the patient who refused chemotherapy in the study. In their response letter, they argue that excluding this patient was impossible due to the "already extremely low number of cases" . They added a limitation statement instead of removing the patient.

Author Response

Budapest, February 11, 2026.

 

 

Dear Reviewer,

 

On behalf of our fellow Authors, first of all, we would like to thank you for your attention and opinion on our original article entitled “Survival difference of advanced-stage cervical and ovarian cancer patients treated with concomitant modulated electro-hyperthermia in comparison to classic treatment modalities: results of a pilot study and meta-analysis”. Here we provide answers to the comments our Reviewer raised.

 

While they successfully fixed the descriptive and technical flaws (e.g., adding device settings and safety grading), they completely rejected the primary methodological recommendation to separate their pilot data from the meta-analysis. The authors cleaned up the reporting quality (better descriptions, standardized safety metrics) but ignored the scientific validity concern (statistical weight of their own data). By refusing to decouple the pilot study from the meta-analysis, the manuscript still contains the "fatal flaw" identified in the initial review.

The reviewer’s strongest recommendation was to remove the authors' own pilot data from the meta-analysis calculations to avoid "circular validation." In the revised abstract and methods, the authors explicitly state: "The results of our institutional pilot study were incorporated into the meta-analysis" and "In addition, the results presented in the observational part of the current study were also included in the meta-analysis". The "Ovarian Cancer" meta-analysis is still methodologically compromised, as it continues to weight their small, uncontrolled pilot study against published literature.

We thank the Reviewer for their kind words and hard work. In the first revision, we have completely removed our own data from the meta-analysis, as suggested by all Reviewers. This included not only the figures, numeric data etc., but those two sentences as well, which the Reviewer in their report pointed out above. The Editorial Office of the Journal asked us to use the Track-changes function of Word, and we believe that there was some technical issue in the PDF conversion on our side, which may have made it appear that these sentences were left in the manuscript. In the current version, all these sentences were completely removed. We are sorry for this inconvenience.

In the current revision, a clean version of the manuscript was submitted only, and all sections that needed significant editing – including the issue with the patient not receiving chemotherapy – are listed and detailed in this letter.

 

The reviewer noted missing ECOG scores and the issue of including patients who "refused" standard care. They added that "all patients had an ECOG performance score of 0", which clarifies the baseline health of the cohort. They kept the patient who refused chemotherapy in the study. In their response letter, they argue that excluding this patient was impossible due to the "already extremely low number of cases" . They added a limitation statement instead of removing the patient.

We thank the Reviewer for their criticism. The patient suggested by the Reviewer was removed from the analysis. Due to this, the following parts of the manuscript were edited / removed:

• In Methods the number of cases – where mentioned – was corrected reflecting the removal of 1 patient from the case series.
• Between lines 173 – 190 all the data related to the patient refusing treatments were completely removed.
• Table 1: The second row with the details of the patient was deleted. Numbering of patients was corrected to reflect the removal.
• Figure 1 (survival curves of the case report patient) was completely removed.
• The following sentence was removed from Limitations: “Further limitations included the fact that one of the seven patients refused several types of oncological treatments, which could introduce some patient selection-bias, as such patients have significantly higher prognostic risk.”

 

Yours sincerely,

 

Dr. A. Marcell Szasz and Dr. Zoltan Herold

Semmelweis University

Round 3

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have fully corrected the "fatal flaw." The manuscript now correctly reports a Meta-Analysis of the literature and a separate Pilot Case Series, without mathematically mixing them. The circular validation issue is no longer present.

• • Previous Version (v2):

Explicitly stated, "The results of our institutional pilot study were incorporated into the meta-analysis."

Total 35 patients (31 from literature + 4 pilot).

• • Current Version (v3):

This statement has been removed. The text now clearly distinguishes the two components: "Methods: A single-institute pilot case series and a meta-analysis was conducted." It presents them as parallel investigations rather than a merged dataset.

Total 31 patients. This matches exactly the sum of the external studies, confirming the pilot data is excluded.

 

The reviewer previously flagged the inclusion of a non-compliant patient who refused standard chemotherapy as a major confounding factor. The authors removed this patient entirely from the analysis.

Methods: Sample size updated (n=7 -> n=6).

Table 1: The row describing the patient who refused treatment is gone.

Results: Figure 1 (survival curves for that specific patient) has been deleted.

This cleans up the "Selection Bias" issue significantly. The cohort is now more homogeneous (all received standard care + mEHT).

 

The manuscript is methodologically sound.