Review Reports - Radiological and Not Clinical Variables Guide the Surgical Plan in Patients with Glioblastoma

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Summary: The manuscript investigates factors influencing the decision to perform a biopsy or complete resection in glioblastoma patients. The study includes 99 patients and analyzes clinical, radiological, and pathological features to guide surgical planning. The main strength of the paper lies in its focus on a clinically relevant topic with implications for treatment decision-making in glioblastoma patients.

General Comments: The manuscript provides valuable insights into the factors influencing surgical decisions in glioblastoma patients. However, some areas need further clarification and improvement. Firstly, the rationale behind selecting specific variables for analysis should be better justified to enhance the study's scientific rigor. The methodology section could also benefit from more detailed descriptions of the data collection process and statistical analyses performed. Including information on potential confounders and how they were controlled for would strengthen the validity of the findings. Moreover, discussing the study's limitations, such as selection bias or missing data, would provide a more comprehensive interpretation of the results.

Specific Comments:

Introduction: The impact of the maximal extent of resection on survival is highlighted, but the specific criteria used to define the maximal extent of resection need to be clearly outlined. Including a brief description of how the extent of resection was determined in the study population would strengthen the interpretation of the results.

Methods: The rationale for choosing ring enhancement and edema volume as key radiological variables associated with complete resection could be further elaborated to provide a clearer justification for their selection.

Under the heading Radiological variable evaluation: Please provide more details on the criteria used to define corpus callosum or internal capsule involvement, as these factors were identified as significant in the analysis.

Table 3: The odds ratios for age and gender in the univariate analysis are provided, but interpreting these results in the context of surgical decision-making is not discussed. Elaborate on the potential implications of age and gender as factors influencing the choice between biopsy and resection.

The discussion on corpus callosum involvement and its association with prognosis in the complete resection group could be expanded to discuss potential underlying mechanisms or biological implications.

The discussion on the impact of KPS on surgical decision-making could be expanded to consider the dynamic nature of KPS throughout treatment. Exploring how changes in KPS during the treatment trajectory may influence the decision for biopsy or resection would add depth to the analysis.

When discussing the study's limitations, could you consider addressing the potential impact of selection bias due to the retrospective nature of the analysis and suggest strategies for mitigating this limitation in future research?

The authors can summarize the discussion by emphasizing the role of multidisciplinary tumor boards or shared decision-making processes involving neurosurgeons, oncologists, and patients in treatment. Including a brief discussion on the collaborative decision-making approach could enrich the conclusion.

The conclusion could be strengthened by emphasizing the clinical implications of the study findings and how they can inform treatment decisions in glioblastoma patients.

The manuscript presents important findings on factors influencing the surgical plan in glioblastoma patients. Addressing the points mentioned above would enhance the clarity and robustness of the study, making it a valuable contribution to the field of neuro-oncology.

Comments on the Quality of English Language

Moderate level of English editing required. Please run a proofreading software like Grammarly.

Author Response

Thank you very much for all your comments and contributions to this work. They have allowed us to significantly improve the presentation and discussion of our results. Below, we address each of your specific comments one by one.

Introduction: The impact of the maximal extent of resection on survival is highlighted, but the specific criteria used to define the maximal extent of resection need to be clearly outlined. Including a brief description of how the extent of resection was determined in the study population would strengthen the interpretation of the results.

Thank you very much for this contribution. In this study, like most works, the extent of resection is considered in relation to the volume of residual contrast enhancement. As indicated in the methodology section (section 2.5), complete resection has been considered when at least 99% of the volume of contrast enhancement has been removed. However, in recent years, there has been a trend towards supramaximal resections, meaning not only removing the entirety of the contrast enhancement volume but also part of the surrounding area radiologically corresponding to hyperintensity on FLAIR sequence. Supramaximal resections appear to be associated with better prognosis (Mier-García JF, J Neurooncol., 2023). In our study, some patients included in the complete resection group may be considered as having undergone supramaximal resections. However, since the aim of the study was to analyze surgical intention regarding the type of resection to be performed, we have decided not to delve into this aspect. Nonetheless, we have added a sentence in the introduction to clarify what we mean by maximal extent of resection.

Methods: The rationale for choosing ring enhancement and edema volume as key radiological variables associated with complete resection could be further elaborated to provide a clearer justification for their selection.

Regarding the assessment of radiological studies, in addition to the variables you mentioned, we included the volume of contrast enhancement, the volume of necrosis, and the presence of heterogeneous contrast enhancement. With this evaluation (quantitative and qualitative), we believe we conducted a comprehensive assessment of the tumor's intrinsic characteristics, surpassing even the information provided by standard radiological reports. The reason for including radiological variables in our study analysis lies in the fact that magnetic resonance imaging (MRI) is the imaging modality of choice for initial diagnosis of a brain tumor, and it is from MRI that the cascade of decisions in these cases begins. We have included a brief statement regarding this in the methodology section (Section 2.5).

Under the heading Radiological variable evaluation: Please provide more details on the criteria used to define corpus callosum or internal capsule involvement, as these factors were identified as significant in the analysis.

Thank you for this recommendation. Both corpus callosum involvement and proximity to the internal capsule were assessed by jointly analyzing T1-weighted MRI images with and without contrast enhancement, along with T2/T2-FLAIR-weighted MRI images and diffusion tensor imaging (fractional anisotropy map). We have included this information in the manuscript.

Table 3: The odds ratios for age and gender in the univariate analysis are provided, but interpreting these results in the context of surgical decision-making is not discussed. Elaborate on the potential implications of age and gender as factors influencing the choice between biopsy and resection.

Indeed, both age and gender were included in the univariate analysis, but none of the estimated odds ratios for these variables were statistically significant. Similarly to how neurological condition appears to have no influence on surgical decision-making, neither age nor gender seem to be variables that influence it. Some comments on this matter were already included in the study's discussion.

The discussion on corpus callosum involvement and its association with prognosis in the complete resection group could be expanded to discuss potential underlying mechanisms or biological implications.

Thank you for this suggestion. It has been suggested that infiltration of the corpus callosum may facilitate increased dissemination of tumor cells, potentially influencing the efficacy of complete surgical resection and, consequently, patient prognosis. Additionally, involvement of the corpus callosum could be associated with impairment of specific brain functions, such as sensory and motor integration, as well as higher cognitive functions. Therefore, the presence of corpus callosum involvement could have direct implications for patients' quality of life and functional recovery after surgery.

In addition to what we had already included in the discussion, we have added some clarifying statements regarding this matter.

The discussion on the impact of KPS on surgical decision-making could be expanded to consider the dynamic nature of KPS throughout treatment. Exploring how changes in KPS during the treatment trajectory may influence the decision for biopsy or resection would add depth to the analysis.

We appreciate the insightful comment from the reviewer. While our study did not find a direct relationship between surgical intention and preoperative Karnofsky Performance Status (KPS) or the presence of neurological symptoms, it is essential to consider the dynamic nature of KPS throughout the treatment trajectory.

KPS serves as a crucial clinical tool for assessing functional status and guiding treatment decisions in patients with glioblastoma. Throughout the course of treatment, KPS may fluctuate in response to various factors such as tumor progression, treatment-related side effects, and overall disease burden.

Understanding how changes in KPS over time influence surgical decision-making is paramount. For instance, initial biopsy may be preferred in patients with lower KPS to minimize surgical risk and maximize quality of life. Conversely, in cases where KPS improves with adjuvant therapies or surgical intervention, the decision for more extensive resection may be warranted to capitalize on potential functional gains and improve long-term outcomes.

By exploring the dynamic nature of KPS throughout treatment, we can gain a deeper understanding of its impact on surgical decision-making strategies.

We have included part of this reflection in the manuscript.

When discussing the study's limitations, could you consider addressing the potential impact of selection bias due to the retrospective nature of the analysis and suggest strategies for mitigating this limitation in future research?

We acknowledge the reviewer's concern regarding potential selection bias due to the retrospective nature of our analysis. To mitigate this limitation in future research, prospective cohort studies with standardized data collection protocols, multicenter collaborations and sensitivity analyses are recommended. Implementing these strategies can enhance the validity and generalizability of study findings in the investigation of glioblastoma management and outcomes. We have included this information in the manuscript.

The authors can summarize the discussion by emphasizing the role of multidisciplinary tumor boards or shared decision-making processes involving neurosurgeons, oncologists, and patients in treatment. Including a brief discussion on the collaborative decision-making approach could enrich the conclusion.

Thank you for this interesting insight. Indeed, we agree on the important role that tumor boards play in therapeutic decision-making for patients with glioblastoma. We have included a reflection on this at the end of the discussion.

The conclusion could be strengthened by emphasizing the clinical implications of the study findings and how they can inform treatment decisions in glioblastoma patients.

Thank you for this note. We have modified the conclusion to include the clinical implications of our work.

Moderate level of English editing required. Please run a proofreading software like Grammarly.

The article has been reviewed and edited by one or more highly qualified native English-speaking editors.

Reviewer 2 Report

Comments and Suggestions for Authors

In this study of patients with glioblastoma, the decision to perform a biopsy or complete resection (CR) was influenced by various factors.

Overall, the study underscores the importance of radiological assessment in guiding treatment decisions for glioblastoma patients and suggests the need for further research to refine the decision-making process and improve patient outcomes.

Overall good work.

Congratulations to the authors

Author Response

Thank you very much for your comments. We greatly appreciate them.

Reviewer 3 Report

Comments and Suggestions for Authors

Regarding the full text :

The Introduction is well written and provides all the necessary data for further readings of the paper .

Methods : Although the indication criteria for biopsy or resection are the expected final results of the study , at least a short information about the presurgical decision making proces should be provided – e.g. the role aof age , clinical status, tumor location and probably also the philosophy of the involved neurosurgeons. Otherwise the methodology is well described (postsurgical CT to exclude complication not performed ?) and the principles of care of glioblastoma patients are fully respected.

Results – Table 23 – the term volumen is incorrect

Discussion : the authors are well aware of the limitations of their study. However despite their statistically supported results I would weaken the statement that the clinical situation of the patient is the key for choosing one approach (biopsy or resection) or the other. Surgical resection is not an option in situation of patient with e.g. critical heart condition or liver problems limiting the possibilities o fat least three hours general anaesthesia.

Author Response

Methods : Although the indication criteria for biopsy or resection are the expected final results of the study , at least a short information about the presurgical decision making proces should be provided – e.g. the role aof age , clinical status, tumor location and probably also the philosophy of the involved neurosurgeons. Otherwise the methodology is well described (postsurgical CT to exclude complication not performed ?) and the principles of care of glioblastoma patients are fully respected.

Thank you for this comment. We have included information regarding the two points you mentioned in the methodology section.

Results – Table 23 – the term volumen is incorrect

Corrected.

Discussion : the authors are well aware of the limitations of their study. However despite their statistically supported results I would weaken the statement that the clinical situation of the patient is the key for choosing one approach (biopsy or resection) or the other. Surgical resection is not an option in situation of patient with e.g. critical heart condition or liver problems limiting the possibilities o fat least three hours general anaesthesia.

Thank you for this contribution. We have included a clarification to this effect in the discussion.