Anatomy-Guided Microsurgical Resection of a Dominant Frontal Lobe Tumor Without Intraoperative Adjuncts: A Case Report from a Resource-Limited Context

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The authors reported the case of a 21-year-old right-handed male who presented with progressive non-fluent aphasia, seizures, and signs of intracranial hypertension. The details of the dominant frontal glioblastoma were described.

The manuscript was well-written with sufficient discussion of facts.

In the introduction section, please include the latest WHO classification of adult-type diffuse gliomas.

Did the patient have anosmia?

What is the outcome of surgery when done at an earlier or at a later stage?

During surgery, any special mention of the frontal sinus?

What may be the common complications of surgery? They could be added to the discussion section.

What can be the most important prognostic markers?

Author Response

Reviewer Comment 1:

“The authors reported the case of a 21-year-old right-handed male who presented with progressive non-fluent aphasia, seizures, and signs of intracranial hypertension. The details of the dominant frontal glioblastoma were described. The manuscript was well-written with sufficient discussion of facts.”

Response:
We are deeply grateful for this generous overall appraisal of our manuscript. Your recognition of the clarity of presentation and adequacy of discussion encourages us to continue refining the work in line with your thoughtful suggestions.

Reviewer Comment 2:

“In the introduction section, please include the latest WHO classification of adult-type diffuse gliomas.”

Response:
We thank you for this important suggestion. We have now revised the Introduction to explicitly integrate the most recent WHO 2021 classification, highlighting that adult-type diffuse gliomas are divided into three major categories: astrocytoma, IDH-mutant; oligodendroglioma, IDH-mutant and 1p/19q-codeleted; and glioblastoma, IDH-wildtype. This addition situates our case within the current molecular diagnostic framework and ensures alignment with contemporary international standards.

Reviewer Comment 3:

“Did the patient have anosmia?”

Response:
We appreciate this highly relevant question. Intraoperatively, the olfactory tract was carefully preserved, as noted in the surgical description. Postoperatively, the patient did not report subjective anosmia, and olfactory function appeared clinically intact. We have now explicitly clarified this detail in the Case Description to strengthen the completeness of the clinical account.

Reviewer Comment 4:

“What is the outcome of surgery when done at an earlier or at a later stage?”

Response:
We are grateful for this opportunity to expand the discussion. 

Reviewer Comment 5:

“During surgery, any special mention of the frontal sinus?”

Response:
Thank you for raising this practical surgical consideration. In our patient, the frontobasal craniotomy did not require entry into the frontal sinus, and the sinus was preserved without violation. We have clarified this point within the Case Description, as it is an important anatomical and technical detail for reproducibility.

Reviewer Comment 6:

“What may be the common complications of surgery? They could be added to the discussion section.”

Response:
We fully agree with this valuable suggestion. 

Reviewer Comment 7:

“What can be the most important prognostic markers?”

Response:
We are grateful for this academically significant observation. In response, we have enriched the Discussion by including a section on prognostic markers in GBM.

Reviewer 2 Report

Comments and Suggestions for Authors

 

1. The introduction is highly current and comprehensive, citing the latest sources (CBTRUS, GLOBOCAN, WHO 2021, 2024 data).

2. The global context and healthcare disparities are well addressed, with clear emphasis on differences in access to treatment.

3. The introduction is too long and overly detailed for a case report.

4. Several topics (immunotherapy, PD-L1, T-cell exhaustion, AI tools such as DeepGlioma, treatment costs) will not be discussed in the case and unnecessarily extend the introduction.

5. Sentences are overly complex and verbose, which reduces clarity.

6. Logical flow needs improvement; the text currently jumps between epidemiology, biomarkers, immunotherapy, AI, costs, and surgery without a clear structure.

7. The table presented is unclear and requires better formatting for readability.

Comments on the Quality of English Language

1. Sentences are overly complex and verbose; some sound literary rather than scientific (e.g., “after the intra-operative technology has superseded the constraints…”).
2. The table presented is unclear and requires better formatting for readability.

Author Response

Response to Reviewer

We are deeply grateful to the reviewer for the generous and constructive feedback on our manuscript. Your comments have been invaluable in helping us refine the clarity, focus, and readability of this report. We have carefully addressed each point as outlined below:

Introduction currency and comprehensiveness
We sincerely thank you for recognizing that the Introduction incorporated up-to-date sources (CBTRUS, GLOBOCAN, WHO 2021, and recent 2024 data). We also greatly appreciate your observation that global disparities in access to treatment were highlighted, as this remains a central theme of the case.

Length and level of detail of the Introduction
We fully agree that the Introduction was overly detailed for a single-patient case report. In response, we have substantially streamlined this section, focusing more sharply on the clinical problem of glioblastoma management, the role of adjuncts, and the challenges in low-resource settings. Sections on immunotherapy, PD-L1, T-cell exhaustion, AI tools (e.g., DeepGlioma), and cost analyses were removed, as they extended beyond the scope of the case.

Sentence structure and clarity
Thank you for pointing out that some sentences were overly complex. We have carefully revised the Introduction (and relevant sections of the Discussion) to shorten and clarify sentences, improving fluency while preserving essential academic detail.

Logical flow of the Introduction
We appreciate this insightful observation. 

Formatting of the table
We are sincerely grateful for this valuable comment. The table has been fully reformatted for clarity and condensation. 

Reviewer 3 Report

Comments and Suggestions for Authors

This manuscript presents a case report of a patient with glioblastoma treated by subtotal resection using a purely anatomy-guided surgical approach, without the aid of modern adjuncts such as neuronavigation, intraoperative ultrasound, or fluorescence guidance. The authors provide detailed preoperative imaging, operative description, and postoperative outcome. They argue that anatomy-based techniques remain valid and may allow safe and effective surgery in resource-limited settings. The case is carefully documented, and the clinical relevance is clear, but several aspects of the presentation and discussion require clarification and improvement to strengthen the manuscript.

 

• It is recommended to streamline the introduction. While comprehensive, it includes lengthy epidemiological and molecular background that goes beyond the needs of a single-patient case report. Please focus more sharply on the clinical problem (glioblastoma management, role of adjuncts, and challenges in low-resource settings).
• Please provide more detail on intraoperative decision-making: how was the extent of resection judged intraoperatively, and what criteria were used to stop resection and classify the outcome as “subtotal” rather than “gross total”? This would increase the reproducibility and educational value of the report.
• It is recommended to improve figure quality and clarity. Some MRI images are low resolution. Please consider adding arrows/annotations to highlight key anatomical landmarks or residual tumor areas. Scale bars would also be useful.
• The conclusion that anatomy-guided surgery can be “safe and effective” should be moderated. This is a single case, and while illustrative, it cannot demonstrate general equivalence to adjunct-assisted resection. Please reframe the conclusion to emphasize the feasibility of anatomy-based approaches in specific circumstances, rather than suggesting a general alternative.
• Please clarify the length and completeness of follow-up. Survival data, functional outcomes, and quality of life measures would strengthen the case. If the patient is still alive, please indicate the most recent follow-up date.
• The English is generally understandable but somewhat verbose. Shortening and clarifying sentences, particularly in the Introduction and Discussion, would improve readability.

• Please unify terminology for extent of resection (subtotal vs. partial vs. gross total) and define the percentage of tumor removed if possible.
• Ensure consistency in abbreviations (e.g., MRI, CT, GBM).
• Clarify whether adjuvant treatment (radiotherapy, temozolomide) was administered, as this is standard of care and critical for contextualizing the outcome.
• Review figure legends for completeness, each should be interpretable without referring back to the main text.

Author Response

Reviewer Comment 1

“It is recommended to streamline the introduction. While comprehensive, it includes lengthy epidemiological and molecular background that goes beyond the needs of a single-patient case report. Please focus more sharply on the clinical problem (glioblastoma management, role of adjuncts, and challenges in low-resource settings).”

Response:
We are sincerely grateful for this insightful recommendation. Your guidance helped us to refine the focus of the Introduction and bring it more directly to the clinical challenges of glioblastoma management, particularly in low-resource settings. We carefully shortened the epidemiological and molecular sections, retaining only the most essential background, and placed greater emphasis on the clinical problem, the role of adjuncts, and the reality of anatomy-guided approaches in centers without advanced resources. We believe this has considerably improved the clarity and relevance of the Introduction.

Reviewer Comment 2

“Please provide more detail on intraoperative decision-making: how was the extent of resection judged intraoperatively, and what criteria were used to stop resection and classify the outcome as ‘subtotal’ rather than ‘gross total’? This would increase the reproducibility and educational value of the report.”

Response:
We are deeply appreciative of this important suggestion. We have now expanded the Surgical Procedure section to include a detailed description of intraoperative decision-making. Specifically, we describe how the extent of resection was judged in real time through visual, tactile, and anatomical cues, and outline the reproducible “stop criteria” that led us to classify the resection as subtotal. These included the disappearance of a safe cleavage plane, the appearance of critical vascular structures, increasing tissue resistance suggesting eloquent pathways, and the proximity of midline and subcallosal structures. We agree that this addition strengthens the educational value of the report and provides greater transparency for readers.

Reviewer Comment 3

“It is recommended to improve figure quality and clarity. Some MRI images are low resolution. Please consider adding arrows/annotations to highlight key anatomical landmarks or residual tumor areas. Scale bars would also be useful.”

Response:
We thank the reviewer for this constructive feedback. We added arrows to highlight key anatomical landmarks, margins of resection cavities, and areas of radiological interest. Figure legends were updated accordingly to explain each annotation in detail, so that every image is now interpretable on its own without reference to the main text.

Reviewer Comment 4

“The conclusion that anatomy-guided surgery can be ‘safe and effective’ should be moderated. This is a single case, and while illustrative, it cannot demonstrate general equivalence to adjunct-assisted resection. Please reframe the conclusion to emphasize the feasibility of anatomy-based approaches in specific circumstances, rather than suggesting a general alternative.”

Response:
We are very grateful for this wise and balanced observation. We fully agree and have reframed the Conclusion to avoid overgeneralization. The revised version emphasizes feasibility rather than equivalence: this case illustrates how anatomy-based microsurgery can remain a viable and valuable strategy in carefully selected patients, particularly in low-resource settings where adjuncts may not be available. We hope the new wording conveys a more measured and academically responsible conclusion, in line with the reviewer’s recommendation.

Reviewer Comment 5

“Please clarify the length and completeness of follow-up. Survival data, functional outcomes, and quality of life measures would strengthen the case. If the patient is still alive, please indicate the most recent follow-up date.”

Response:
We are thankful for this suggestion, which indeed strengthens the case presentation. We have now clarified that follow-up extends to three months postoperatively, at which time the patient remains alive, neurologically stable, and radiologically free of progression. We have also included details of functional recovery, language improvement, seizure status, cognitive function, and daily living independence, as well as observations from the family regarding quality of life. These additions ensure a more complete and clinically meaningful follow-up description.

Reviewer Comment 6

“The English is generally understandable but somewhat verbose. Shortening and clarifying sentences, particularly in the Introduction and Discussion, would improve readability.”

Response:
We sincerely appreciate this constructive observation. In response, we carefully revised the Introduction and Discussion, shortening long sentences and clarifying wording to improve readability while preserving all important clinical and scientific details. We believe the revised text is more fluent and accessible to readers, without losing depth.

Reviewer Comment 7

“Please unify terminology for extent of resection (subtotal vs. partial vs. gross total) and define the percentage of tumor removed if possible.”

Response:
We thank the reviewer for highlighting this important point. 

Reviewer Comment 8

“Ensure consistency in abbreviations (e.g., MRI, CT, GBM).”

Response:
We appreciate this observation. We reviewed the entire manuscript carefully and corrected all abbreviations to ensure uniformity. 




Reviewer Comment 9

“Clarify whether adjuvant treatment (radiotherapy, temozolomide) was administered, as this is standard of care and critical for contextualizing the outcome.”

Response:
We are very grateful for this important comment. We have clarified that, following multidisciplinary consultation, the patient proceeded with standard adjuvant chemoradiotherapy according to the Stupp protocol (external beam radiotherapy with concomitant and adjuvant temozolomide). We emphasize that the favorable neurological recovery after surgery allowed oncological therapy to commence on time, without delay, in accordance with international standards of care.

Reviewer Comment 10

“Review figure legends for completeness, each should be interpretable without referring back to the main text.”

Response:
We thank the reviewer for this valuable suggestion. In response, we revised all figure legends extensively. Each legend now specifies the imaging modality, sequence, anatomical location, arrow annotations, and clinical interpretation. This ensures that each figure is fully self-contained and interpretable without referring to the main text.

Round 2

Reviewer 3 Report

Comments and Suggestions for Authors

I would like to thank the authors for addressing all the comments. I have no further questions or concerns, and I recommend acceptance of the manuscript in its current form.