Incidental Lung Lesions on the CT Component of Oncologic FDG PET/CT: A Pictorial Review of Interpretive Pitfalls and Diagnostic Clues

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This is a clear, clinically useful pictorial review of incidental lung lesions detected on the CT component of oncologic FDG PET/CT. Its strongest feature is the consistent lesion-by-lesion framing: CT morphology, PET/CT concordance, interval change, and the oncologic context are integrated across the principal diagnostic scenarios. The manuscript appropriately emphasizes that low or absent FDG uptake does not establish benignity and that inflammatory and malignant processes may overlap on both CT and PET. The case-based structure, figures, and summary table are well aligned with the stated educational purpose. I recommend minor revision, as I have only few suggestions to improve the manuscript.

1. The manuscript identifies itself as a narrative, case-based pictorial review and states that diagnoses were based on histopathology when available or on imaging/clinical follow-up otherwise. Please specify the minimum follow-up used when pathology was unavailable. In each figure legend, please state explicitly whether the final diagnosis was histologically confirmed or established by a specified clinical/imaging reference standard.

2. The conclusion appropriately notes that the Table is intended to structure lesion-level reasoning rather than provide validated decision rules. Consider changing “Recommended action” to “Suggested diagnostic consideration/action” and explicitly state that timing of CT surveillance, biopsy, and lung-cancer staging should be individualized in a multidisciplinary clinical setting. This would avoid a guideline-like interpretation of recommendations that are intentionally illustrative.

3. In the Abstract and Introduction, the statement that these lesions are “more likely to be malignant” than incidental lesions in the general population is directionally reasonable but could be read as universal. The manuscript itself recognizes that risk depends on index tumor biology, lesion morphology, treatment status, epidemiology, and competing inflammatory/infectious diagnoses. Please revise to “may have a higher pre-test probability of malignancy”.

4. The text states that thin-section reconstruction permits confident morphologic characterization “in most cases,” while later noting important non-contrast and respiratory limitations. Please soften the former wording (for example, “may improve morphologic assessment when diagnostic-quality thin-section reconstructions are available”) and retain a clear statement that PET/CT CT does not substitute for dedicated diagnostic chest CT when contrast enhancement, full lung characterization, or mediastinal/hilar assessment is required.

5. Minor editorial points: 1) Define “ILL” once in the Abstract only if the abbreviation is used thereafter in the Abstract; otherwise, avoid the abbreviation there and retain the full term. 2) Standardize terminology and punctuation. 3) Ensure that all figure legends state the interval between examinations consistently.

Author Response

Dear Editor and Reviewers,

We sincerely thank the Editor and the Reviewers for their careful evaluation of our manuscript and for their constructive comments. We have revised the manuscript substantially in response to the suggestions. The major changes include clarification of the narrative literature-search approach and case-selection framework, specification of the diagnostic reference standards for the illustrative cases, refinement of statements regarding malignancy risk and the limitations of the CT component of PET/CT, revision of Table 1 to avoid a guideline-like interpretation, standardization of the figure legends, and addition of a dedicated Future Directions section. All changes made in response to the reviewers’ comments are highlighted in red in the revised manuscript.

Our point-by-point responses are provided below. The reviewers’ comments are reproduced in italics, followed by our responses.

Reviewer 1

We thank the Reviewer for the positive assessment of the manuscript and for the constructive suggestions, which helped us improve its clarity and clinical applicability.

Comment 1

The manuscript identifies itself as a narrative, case-based pictorial review and states that diagnoses were based on histopathology when available or on imaging/clinical follow-up otherwise. Please specify the minimum follow-up used when pathology was unavailable. In each figure legend, please state explicitly whether the final diagnosis was histologically confirmed or established by a specified clinical/imaging reference standard.

The figure legends were also reviewed and revised to clarify the basis of diagnosis, including histopathologic confirmation, clinicopathologic correlation, microbiologic confirmation, or imaging/biochemical evidence, as applicable. In particular, the Figure 2 legend now explicitly states that the diagnosis was established without histopathologic confirmation on the basis of concordant radioiodine uptake and longitudinal imaging and biochemical changes.

Revised manuscript: pp. 2–3, lines 91–102; Fig. 1, p. 6, lines 270–271; Fig. 2, p. 7, lines 279–282; Fig. 4, p. 8, lines 321–322; Fig. 5, p. 9, lines 349–353; Fig. 6, p. 11, lines 410–412; Fig. 7, p. 13, lines 487–491.

Comment 2

The conclusion appropriately notes that the Table is intended to structure lesion-level reasoning rather than provide validated decision rules. Consider changing “Recommended action” to “Suggested diagnostic consideration/action” and explicitly state that timing of CT surveillance, biopsy, and lung-cancer staging should be individualized in a multidisciplinary clinical setting. This would avoid a guideline-like interpretation of recommendations that are intentionally illustrative.

Response:
We agree and have revised Table 1 accordingly. The column heading “Recommended action” has been changed to “Suggested diagnostic consideration/action.” We have also added a footnote stating that these suggestions represent a literature-informed expert synthesis rather than validated management recommendations.

In addition, the Conclusions now explicitly state that the decisions regarding the timing of CT surveillance, the indication for tissue confirmation, and, when a new primary lung cancer is suspected, the extent of staging work-up should be individualized through multidisciplinary assessment, considering the index malignancy, treatment status, and competing inflammatory or infectious diagnoses.

Revised manuscript: p. 14, lines 537–543; p. 15, Table 1 and lines 552–553.

Comment 3

In the Abstract and Introduction, the statement that these lesions are “more likely to be malignant” than incidental lesions in the general population is directionally reasonable but could be read as universal. The manuscript itself recognizes that risk depends on index tumor biology, lesion morphology, treatment status, epidemiology, and competing inflammatory/infectious diagnoses. Please revise to “may have a higher pre-test probability of malignancy”.

Response:
We agree. The statement has been revised to “may have a higher pre-test probability of malignancy” in the Abstract and in the corresponding discussion in Section 3. We also explicitly note that the actual risk varies according to the index malignancy, lesion characteristics, treatment status, and competing infectious or inflammatory diagnoses.

Revised manuscript: p. 1, lines 16–17; p. 5, lines 220–223.

Comment 4

The text states that thin-section reconstruction permits confident morphologic characterization “in most cases,” while later noting important non-contrast and respiratory limitations. Please soften the former wording (for example, “may improve morphologic assessment when diagnostic-quality thin-section reconstructions are available”) and retain a clear statement that PET/CT does not substitute for dedicated diagnostic chest CT when contrast enhancement, full lung characterization, or mediastinal/hilar assessment is required.

Response:
We agree and have revised Section 2.4 accordingly. The previous statement regarding confident morphologic characterization has been replaced with the more cautious wording that diagnostic-quality thin-section reconstructions may improve morphologic assessment when available.

We have also added an explicit statement that the CT component of PET/CT should not be regarded as a substitute for dedicated diagnostic chest CT when intravenous contrast enhancement, comprehensive lung characterization, or detailed mediastinal or hilar assessment is required.

Revised manuscript: p. 4, lines 184–185; p. 5, lines 206–208.

Comment 5

Minor editorial points: 1) Define “ILL” once in the Abstract only if the abbreviation is used thereafter in the Abstract; otherwise, avoid the abbreviation there and retain the full term. 2) Standardize terminology and punctuation. 3) Ensure that all figure legends state the interval between examinations consistently.

We also revised the figure legends to present the temporal intervals between serial examinations more consistently and to clarify the reference examination where necessary. In particular, the intervals in Figure 4 are now stated relative to the index PET/CT, the prior examinations in Figure 6 are explicitly presented as months before the index PET/CT, and the follow-up intervals for both lesions in Figure 7 are stated directly. The remaining legends already stated intervals relative to an identified index examination

Revised manuscript: p. 2, lines 43–44; Fig. 4, p. 8, lines 318–320; Fig. 6, p. 11, lines 408–409; Fig. 7, p. 13, lines 486–490; p. 15, Table 1.

We again thank the Editor and both Reviewers for their thoughtful and constructive comments. We believe that the revisions have substantially improved the methodological clarity, clinical precision, and educational value of the manuscript.

Sincerely,

Narae Lee, MD, PhD (First author)
Ie Ryung Yoo, MD, PhD (Corresponding author)
on behalf of all authors

Reviewer 2 Report

Comments and Suggestions for Authors

This manuscript presents eight illustrative cases of incidental lung lesions on the CT component of FDG PET/CT in oncology. The exposition is biologically accurate and the cases depict recurrent interpretive pitfalls. The material has educational value. However, I do not believe that the submission satisfies the formal MDPI criteria for a Review article type. In my assessment, the manuscript is more accurately characterised as a retrospective case series with an educational component.

MDPI defines a Review as offering a comprehensive analysis of existing literature, identifying gaps, providing recommendations for future research, and presenting no new unpublished data (https://www.mdpi.com/journal/diagnostics/instructions). This manuscript fails on multiple counts. Eight previously unpublished case figures are presented, which contravenes the "no new data" criterion. No literature search is described, undermining any claim of comprehensiveness. Several quantitative anchors rest on studies 19-25 years old without critical appraisal or narrative synthesis. A dedicated Future Directions section, explicitly recommended in MDPI's Review structure, is absent; the entirety of the future research agenda lies within vague questions embedded in the Conclusions.

Applying the SANRA checklist yields a score of 5/12 (1+1+0+1+1+1), with the lowest scores for literature search description (0/2) and data presentation (1/2). The latter reflects the absence of case denominators, selection criteria, patient demographics, and a structured case summary table.

Table 1 presents "recommended actions" of unclear evidentiary basis. Should the expert opinion be presented without explicit labelling as such? Moreover, what does it add beyond the existing guidance from the AJR Expert Panel Narrative Review (Araujo-Filho et al., 2021)?

The authors are encouraged to consider reclassification or alternative venue (non-MDPI). To my knowledge, even the broader classification of possible MDPI articles does not include pictorial review (https://www.mdpi.com/about/article_types). Alternatively, a major revision would be needed to improve adherence to MDPI review requirements.

Author Response

Dear Editor and Reviewers,

We sincerely thank the Editor and the Reviewers for their careful evaluation of our manuscript and for their constructive comments. We have revised the manuscript substantially in response to the suggestions. The major changes include clarification of the narrative literature-search approach and case-selection framework, specification of the diagnostic reference standards for the illustrative cases, refinement of statements regarding malignancy risk and the limitations of the CT component of PET/CT, revision of Table 1 to avoid a guideline-like interpretation, standardization of the figure legends, and addition of a dedicated Future Directions section. All changes made in response to the reviewers’ comments are highlighted in red in the revised manuscript.

Our point-by-point responses are provided below. The reviewers’ comments are reproduced in italics, followed by our responses.

Reviewer 2

We thank the Reviewer for the careful assessment of the manuscript and for highlighting important issues regarding its scope, review methodology, and distinction from a retrospective case series. We have substantially revised the manuscript to address these concerns and to more clearly establish its structure as a narrative, case-based pictorial review.

Comment 1

This manuscript presents eight illustrative cases of incidental lung lesions on the CT component of FDG PET/CT in oncology. The exposition is biologically accurate and the cases depict recurrent interpretive pitfalls. The material has educational value. However, I do not believe that the submission satisfies the formal MDPI criteria for a Review article type. In my assessment, the manuscript is more accurately characterized as a retrospective case series with an educational component.

MDPI defines a Review as offering a comprehensive analysis of existing literature, identifying gaps, providing recommendations for future research, and presenting no new unpublished data. This manuscript fails on multiple counts. Eight previously unpublished case figures are presented, which contravenes the “no new data” criterion.

Response:
We appreciate the Reviewer’s concern regarding the distinction between a narrative pictorial review and a retrospective case series. We have revised the manuscript to make this distinction more explicit.

The manuscript is intended as a literature-based narrative review in which selected clinical images serve solely to illustrate diagnostic concepts and recurrent interpretive pitfalls. The cases do not constitute a consecutive or otherwise defined clinical cohort, and no prevalence estimates, diagnostic-performance measures, outcome analyses, or statistical inferences are derived from them. The recurrent interpretive pitfalls were defined and contextualized through the literature review, after which representative cases were purposively selected to illustrate these concepts. We have now stated this explicitly in the Scope and Case Selection paragraph.

The evidentiary and interpretive claims of the manuscript are derived from the published literature; the illustrative clinical images function as visual teaching material rather than as a dataset from which new clinical conclusions are generated. We therefore respectfully believe that the manuscript remains appropriately classified as a Review rather than a retrospective case series.

To further clarify this distinction, we have also revised the Institutional Review Board Statement to refer specifically to the retrospective use of de-identified clinical images for this review.

Revised manuscript: pp. 2–3, lines 91–102; p. 16, lines 559–565.

Comment 2

No literature search is described, undermining any claim of comprehensiveness. Several quantitative anchors rest on studies 19–25 years old without critical appraisal or narrative synthesis. A dedicated Future Directions section, explicitly recommended in MDPI’s Review structure, is absent; the entirety of the future research agenda lies within vague questions embedded in the Conclusions.

Response:
We appreciate these comments and have revised the manuscript substantially in response.

First, we have added a dedicated Literature Search paragraph describing the narrative PubMed/MEDLINE search, the principal search concepts, manual review of reference lists, and the criteria used to select relevant publications. We also clarify that recent literature was preferentially incorporated where available, while earlier studies were retained when they provided key evidence for specific morphologic, metabolic, or clinical observations that have not been superseded by more recent data.

We agree that several foundational quantitative studies cited in the manuscript are relatively old. These studies were retained because they directly address specific clinical questions for which comparable contemporary datasets remain limited. At the same time, the manuscript incorporates more recent evidence where available, including contemporary studies addressing PET/CT technique, pulmonary nodule detection, oncologic imaging, and atypical pulmonary metastases. Where older quantitative studies were retained, we have also contextualized their findings within the surrounding discussion, clarifying their scope and limitations where relevant and avoiding the presentation of individual estimates as universally applicable.

Finally, we have created a separate Section 8, “Future Directions.” This section now explicitly identifies several areas requiring further investigation, including respiratory-gated and deep-inspiration breath-hold PET/CT, validation of automated nodule detection and classification tools in oncologic surveillance populations, prospective multicenter correlation of morphologic and metabolic patterns with histopathologic diagnoses, and development of risk-adapted surveillance strategies for pulmonary nodules in patients with known malignancy.

Revised manuscript: p. 2, lines 78–90; p. 5, lines 226–230; p. 14, lines 503–522.

Comment 3

Applying the SANRA checklist yields a score of 5/12 (1+1+0+1+1+1), with the lowest scores for literature search description (0/2) and data presentation (1/2). The latter reflects the absence of case denominators, selection criteria, patient demographics, and a structured case summary table.

Response:
We thank the Reviewer for applying the SANRA framework and agree that the literature-search methodology required clearer description. As noted above, we have therefore added a dedicated description of the narrative literature search.

Instead, we have strengthened the description of case selection and diagnostic verification and have revised the individual figure legends to specify the basis for the final diagnosis and temporal follow-up. We believe that this approach better reflects the educational role of the cases within a narrative pictorial review.

Revised manuscript: pp. 2–3, lines 78–102; figure legends on pp. 6–13.

Comment 4

Table 1 presents “recommended actions” of unclear evidentiary basis. Should the expert opinion be presented without explicit labelling as such? Moreover, what does it add beyond the existing guidance from the AJR Expert Panel Narrative Review (Araujo-Filho et al., 2021)?

Response:
We agree that the original wording could have been interpreted as guideline-like. We have therefore changed the Table 1 column heading from “Recommended action” to “Suggested diagnostic consideration/action.” We have also added a footnote explicitly stating that the suggestions represent a literature-informed expert synthesis rather than validated management recommendations. The Conclusions have been revised accordingly to emphasize individualized clinical decision-making.

We have also clarified the relationship between the present review and the AJR Expert Panel Narrative Review in the Introduction. The two reviews address related but distinct clinical questions. The AJR review addresses the broader management of pulmonary nodules in oncologic patients. The present review has a more specific focus on interpretive problems encountered on the CT component of FDG PET/CT, where CT morphology must be integrated directly with metabolic findings. Particular emphasis is placed on integrating metabolic and morphologic findings, including PET-occult malignant lesions, inflammatory lesions with high FDG uptake, as well as on PET/CT-specific technical issues such as the limitations of commonly used noncontrast or low-dose CT protocols and respiratory misregistration. The review also emphasizes lesion-by-lesion assessment when malignant and benign pulmonary etiologies coexist.

We believe that this PET/CT-focused interpretive framework, reinforced by visual examples, complements rather than duplicates the broader management-oriented guidance provided by the AJR Expert Panel review.

Revised manuscript: p. 2, lines 57–63; p. 14, lines 537–543; p. 15, Table 1 and lines 552–553.

Comment 5

The authors are encouraged to consider reclassification or alternative venue (non-MDPI). To my knowledge, even the broader classification of possible MDPI articles does not include pictorial review. Alternatively, a major revision would be needed to improve adherence to MDPI review requirements.

We also note that Diagnostics has previously published Review articles employing a pictorial presentation, including within the Medical Imaging and Theranostics section. This precedent supports the use of “pictorial” as a description of presentation format within a Review article rather than as a distinct article type..

We hope that these revisions address the Reviewer’s concerns regarding both article classification and adherence to the journal’s expectations for a Review.

Revised manuscript: pp. 2–3, lines 78–102; p. 14, lines 503–522 and 537–543; p. 15, Table 1 and lines 552–553.

We again thank the Editor and both Reviewers for their thoughtful and constructive comments. We believe that the revisions have substantially improved the methodological clarity, clinical precision, and educational value of the manuscript.

Sincerely,

Narae Lee, MD, PhD (First author)
Ie Ryung Yoo, MD, PhD (Corresponding author)
on behalf of all authors

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The authors' revisions are acknowledged. Structural improvements include the Literature Search paragraph, the standalone Future Directions section, Table 1 relabelling, and the Introduction's differentiation from the AJR panel.

A scoring system was applied: 2 = fully addressed, 1 = partially addressed or rebutted with evidence, 0 = unaddressed.

• Comment 1 (article type/new data): 1. Structural revisions made; however, the "no new data" criterion is rebutted without MDPI policy citation. The authors' own Data Availability Statement ("data may be available…upon reasonable request") and Figure Origin Statement ("none of the figures has been previously published") both treat the case material as data.
• Comment 2 (literature search, future directions): 2. Both structural asks fulfilled.
• Comment 3 (SANRA, data presentation): 1. The SANRA cut-off rebuttal cites Baethge et al. (2019), but omits the same paper's statement that scores ≤4 indicate very poor quality. SANRA was designed for peer review use, and I applied it as intended. Denominators declined without adequate justification.
• Comment 4 (Table 1, AJR differentiation): 2. Fully addressed.
• Comment 5 (reclassification/precedent): 0. No specific article or precedent cited. Moreover, a journal's editorial precedent has nothing to do with the reviewer. My role is to assess the manuscript against the journal's stated criteria, guidance for reviewers and established checklists.

New issues to consider:

1. The Literature Search paragraph lists search concepts and searches only PubMed/MEDLINE, but does not provide the search string. This would aid study reproducibility as a review.
2. The Data Availability Statement is inconsistent with the authors' argument that case material is not data.
3. The Future Directions section, while now standalone, contains no specific hypotheses or proposed study designs.

Overall score: 6/10. Improved, but the article-type mismatch persists.

I do not believe that the authors have addressed all the suggestions in good faith. I therefore leave it to the Editor to decide whether an exception to the criteria of Diagnostics is warranted in this particular case.

Author Response

Dear Editor and Reviewers,

We sincerely thank the Editor and the Reviewer for the continued careful evaluation of our manuscript. We have revised the manuscript in response to the new issues raised in this round. The principal changes include clarification of the Boolean combination framework used in the Literature Search paragraph, revision of the Data Availability Statement, and addition of an explicit hypothesis and proposed study design to the Future Directions section. Changes made in this revision are highlighted in blue; changes from the previous revision remain in red.

Our point-by-point responses are provided below. The Reviewer’s comments are reproduced in italics, followed by our responses.

Reviewer 2

We thank the Reviewer for the continued careful assessment of the manuscript and for acknowledging the structural improvements made in the previous revision. We have addressed each of the three new issues raised and respond to the remaining points below.

General assessment

The authors' revisions are acknowledged. Structural improvements include the Literature Search paragraph, the standalone Future Directions section, Table 1 relabelling, and the Introduction's differentiation from the AJR panel.

A scoring system was applied: 2 = fully addressed, 1 = partially addressed or rebutted with evidence, 0 = unaddressed.

Response:
We thank the Reviewer for acknowledging the structural revisions made in response to the previous review. We address the remaining concerns and the three new issues individually below.

Comment 1

Comment 1 (article type/new data): 1. Structural revisions made; however, the "no new data" criterion is rebutted without MDPI policy citation. The authors' own Data Availability Statement ("data may be available...upon reasonable request") and Figure Origin Statement ("none of the figures has been previously published") both treat the case material as data.

Response:
We have revised the Data Availability Statement to remove the ambiguity identified by the Reviewer. It now reads: “No new data were created or analyzed in this study. Data sharing is not applicable to this article.” We recognize that the previous wording was open to the interpretation described by the Reviewer, and we thank the Reviewer for identifying this inconsistency.

The Figure Origin Statement is intended solely to clarify the authorship, reproduction rights, and prior publication status of the figures. We have therefore retained it unchanged.

Revised manuscript: p. 16, lines 575–576 (Data Availability Statement).

Comment 2

Comment 2 (literature search, future directions): 2. Both structural asks fulfilled.

Response:
We thank the Reviewer for confirming that these points were addressed.

Comment 3

Comment 3 (SANRA, data presentation): 1. The SANRA cut-off rebuttal cites Baethge et al. (2019), but omits the same paper's statement that scores ≤4 indicate very poor quality. SANRA was designed for peer review use, and I applied it as intended. Denominators declined without adequate justification.

With respect to denominators and aggregate patient demographics, as explained in our previous response and clarified in the manuscript, the illustrative cases were purposively selected and do not constitute a defined source population. We therefore believe that providing a denominator or aggregate demographic profile would imply a cohort structure that was not used and could be misleading (Scope and Case Selection, p. 3, lines 94–105). We recognize that the Reviewer does not find this rationale persuasive and respectfully leave this point for the Academic Editor’s consideration.

Comment 4

Comment 4 (Table 1, AJR differentiation): 2. Fully addressed.

Response:
We thank the Reviewer for confirming that these points were addressed.

Comment 5

Comment 5 (reclassification/precedent): 0. No specific article or precedent cited. Moreover, a journal's editorial precedent has nothing to do with the reviewer. My role is to assess the manuscript against the journal's stated criteria, guidance for reviewers and established checklists.

Response:
We acknowledge the Reviewer’s view that journal precedent is ultimately a matter for editorial consideration. We have accordingly provided the relevant published examples in our cover letter for the Academic Editor, and respectfully defer the question of article-type classification to the Editor.

New issues to consider

New issue 1

1. The Literature Search paragraph lists search concepts and searches only PubMed/MEDLINE, but does not provide the search string. This would aid study reproducibility as a review.

Response:
We agree that our previous description did not make sufficiently clear how the search terms were combined. Because this was a narrative review, the literature search was conducted iteratively using combinations of the listed terms rather than a single prespecified search string. We have therefore clarified how the search terms were combined using Boolean operators. The Literature Search paragraph now states: "Searches were conducted iteratively using Boolean combinations of the listed terms. In general, (‘FDG PET/CT’ OR ‘oncologic imaging’) was combined with one or more lesion-, disease-, mimic-, or technical-factor terms using AND, while related terms within each concept were combined with OR." The individual search terms, database, search period, reference-list screening, and selection criteria are also specified in the same paragraph.

Revised manuscript: pp. 2–3, lines 78–93 (Literature Search).

New issue 2

2. The Data Availability Statement is inconsistent with the authors' argument that case material is not data.

Response:
Addressed under Comment 1 above.

New issue 3

3. The Future Directions section, while now standalone, contains no specific hypotheses or proposed study designs.

Response:
We have added an explicit hypothesis and proposed study design to the Future Directions section. Specifically, we suggest testing whether lesion-level models integrating CT morphology, FDG avidity, primary tumor histology, and interval growth outperform metabolic assessment alone in discriminating malignant from benign pulmonary lesions. A prospective multicenter study could enroll consecutive patients undergoing staging or surveillance PET/CT, with a prespecified reference standard based on histopathologic confirmation or, when pathology is unavailable, protocol-defined longitudinal imaging criteria over a prespecified minimum follow-up interval. Outcomes could include diagnostic accuracy, biopsy utilization, time to definitive diagnosis, and changes in clinical management attributable to pulmonary lesion characterization.

Revised manuscript: p. 14, lines 521–531 (Future Directions).

Overall assessment

Overall score: 6/10. Improved, but the article-type mismatch persists.

I do not believe that the authors have addressed all the suggestions in good faith. I therefore leave it to the Editor to decide whether an exception to the criteria of Diagnostics is warranted in this particular case.

Response:
We appreciate the Reviewer’s continued assessment. We have addressed the three new issues raised in this round and have provided our responses to the remaining points above. We respectfully defer the question of article-type classification to the Academic Editor.

We again thank the Editor and the Reviewer for their time and attention devoted to this manuscript.

Sincerely,

Narae Lee, MD, PhD (First author)
Ie Ryung Yoo, MD, PhD (Corresponding author)
on behalf of all authors