A Simple Overview of Pancreatic Cancer Treatment for Clinical Oncologists

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

In their review manuscript titled " A Simple Overview of Pancreatic Cancer Treatment for Clinical Oncologists," Garajova et al. aimed to provide practical assistance to clinical oncologists by summarizing the current approaches to managing pancreatic ductal adenocarcinoma (PDAC). The authors employed an elementary framework based on Anatomical resectability, Biological resectability, and Clinical conditions to facilitate understanding and application of the treatment strategies.

This encompasses a substantial, comprehensive, and extensively reasoned corpus of work that is commendable. Nevertheless, there are minor concerns that could be addressed in order to enhance the overall quality of the article. These concerns are outlined below.

1.      In the First-line treatment paradigm, it is recommended that the authors include references to recurrence and chemoresistance when discussing the use of 5-FU and gemcitabine.

2.      Plasma microRNA (miRNA) biomarkers are now gaining recognition as a valuable technique for the early-stage identification of pancreatic ductal adenocarcinoma (PDAC). Please provide a short paragraph about the subject matter.

3.      Some recent research has been conducted on the potential miRNA biomarkers that can be referenced.

a)      doi: 10.1158/1940-6207.CAPR-20-0303

b)     doi: 10.3390/ijms22094765

c)      doi: 10.1001/jama.2013.284664.

Comments on the Quality of English Language

There is room for grammatical improvement.

Author Response

1. In the First-line treatment paradigm, it is recommended that the authors include references to recurrence and chemoresistance when discussing the use of 5-FU and gemcitabine. We included these references.
2. Plasma microRNA (miRNA) biomarkersare now gaining recognition as a valuable technique for the early-stage identification of pancreatic ductal adenocarcinoma (PDAC). Please provide a short paragraph about the subject matter. We introduced this topic to our review as a part of future directions as (unfortunately) in clinical practice we do not base our decisions on biomarkers different than CA 19-9 biomarker.
3. Some recent research has been conducted on the potential miRNA biomarkers that can be referenced. We introduced these articles into our review, thank you.

Reviewer 2 Report

Comments and Suggestions for Authors

The article titled "A Simple Overview of Pancreatic Cancer Treatment for Clinical Oncologists" provides an overview of the treatment options for pancreatic cancer. While the topic is undoubtedly important and relevant, this review raises concerns regarding the article's contribution to the current knowledge in the field and the methodology used to present information.

Strengths:

1. Clarity and Accessibility: The article does a commendable job of presenting complex information in a straightforward and accessible manner. It can serve as a useful resource for clinical oncologists looking for a concise overview of pancreatic cancer treatment options.

Weaknesses: 

1. Lack of Novelty:Perhaps the most significant issue with this article is the lack of novelty. It does not appear to contribute any new insights or information to the existing body of knowledge on pancreatic cancer treatment. Given the vast amount of literature and research on this topic, it is essential for any new article to bring something novel to the table.

2. ABC Method: The article introduces the ABC Method as a framework for evaluating treatment options for pancreatic cancer. However, it is concerning that this method is not evidence-based and may potentially mislead clinical oncologists. The absence of a solid scientific foundation for this approach is a significant drawback.

3. Oversimplification: While simplicity can be beneficial, there is a risk of oversimplification in this article. Pancreatic cancer is a complex disease with various treatment modalities, and an oversimplified approach may not adequately prepare clinical oncologists for the complexities they may encounter in practice.

Recommendations:

1. Novelty and Evidence-Based Approach: To improve the quality and relevance of the article, the authors should consider conducting a thorough literature review to identify gaps in the existing knowledge and offer evidence-based recommendations. If the ABC Method is to be retained, it should be thoroughly validated through clinical studies.

2.Enhanced Referencing: The authors should ensure that all claims and recommendations are supported by references from reputable sources. This will enhance the credibility of the article and provide readers with the opportunity to delve deeper into specific aspects of treatment.

3. Balanced Approach: While maintaining simplicity, the article should strive for a balanced presentation of treatment options, considering the complexities and nuances of pancreatic cancer management.

Author Response

1. Novelty and Evidence-Based Approach:To improve the quality and relevance of the article, the authors should consider conducting a thorough literature review to identify gaps in the existing knowledge and offer evidence-based recommendations. If the ABC Method is to be retained, it should be thoroughly validated through clinical studies.

We agree that there is a lack of evidence-based recommendations for many treatment aspects of pancreatic cancer. This is what makes treatment of this cancer even more difficult and which makes our patients feel less safe compared to other solid tumors. We lack evidence-based recommendation on phase III clinical trials for many clinical questions in pancreatic cancer: starting with head-to-head comparison of gemcitabine-nab/paclitaxel vs mFOLFIRINOX in the first-line, maintenance therapies after first-line, treatment sequences, the role of neoadjuvant treatment in resectable pancreatic treatment, duration of the neoadjuvant treatment, and we have to copy also with regulatory issues. The standard-of-care still remains chemotherapy only for the majority of the patients with important side effects, ev formulations. 

2.Enhanced Referencing: The authors should ensure that all claims and recommendations are supported by references from reputable sources. This will enhance the credibility of the article and provide readers with the opportunity to delve deeper into specific aspects of treatment.

We carefully revised our manuscript and enhaced referencing.

3. Balanced Approach: While maintaining simplicity, the article should strive for a balanced presentation of treatment options, considering the complexities and nuances of pancreatic cancer management.

We agree that pancreatic cancer is an extremely complex disease and extremely difficult to treat in clinical practice for multiple clinical problems and hopeless vision of close future. The main aim of our article was to help the clinical oncologists to obtain the maximum efficacy from actual therapeutic arms and to avoid “big errors” that we see still often in our clinical practice. Thank you for your time and suggestions.

Reviewer 3 Report

Comments and Suggestions for Authors

Summary of the Manuscript:

Reviewed manuscript titled "A Simple Overview of Pancreatic Cancer Treatment for Clinical Oncologists" by Ingrid Garajová, et. al. The manuscript provides a comprehensive review of the current management strategies for Pancreatic Ductal Adenocarcinoma (PDAC), one of the most aggressive solid tumors. The authors introduce a practical "ABC method" for managing PDAC, where A stands for Anatomical respectability, B for Biological respectability, and C for Clinical conditions. The paper discusses the standard-of-care for different stages of PDAC, including respectable, borderline respectable, locally advanced, and metastatic stages. The authors also touch upon the role of various treatment modalities such as surgery, chemotherapy, and chemoradiotherapy, and highlight the importance of a multidisciplinary approach in decision-making.

Strengths:

• The manuscript is well-structured and provides a clear and concise overview of the current treatment strategies for PDAC.
• The introduction of the "ABC method" offers a practical approach for clinicians to categorize and manage PDAC patients.
• The authors have provided a comprehensive discussion on the role of surgery, chemotherapy, and chemoradiotherapy, making it a valuable resource for clinical oncologists.
• The inclusion of recent studies and trials ensures that the review is up-to-date with the latest evidence-based practices.

Weaknesses:

• The manuscript could benefit from a more detailed discussion on the molecular and genetic aspects of PDAC, which are crucial for personalized treatment strategies.
• The paper does not delve deep into the potential side effects and complications associated with the various treatment modalities.
• The role of emerging therapies and targeted treatments is not adequately covered.

Recommendations:

• The authors should consider expanding the discussion on the molecular and genetic markers of PDAC, as they play a pivotal role in treatment decision-making.
• A section dedicated to the potential side effects, complications, and management of the same for each treatment modality would enhance the manuscript's utility for clinicians.

• It would be beneficial to include a discussion on emerging therapies, targeted treatments, and ongoing clinical trials in the field of PDAC.
• The figures 3 could be better labeled and formatted for clarity.
• Some sections, especially the introduction, could benefit from a more detailed background on PDAC's epidemiology and pathophysiology.
• The authors should consider adding patient case studies or real-world examples to illustrate the application of the "ABC method."

Conclusion:

The manuscript provides a valuable overview of the current treatment strategies for PDAC, introducing a practical approach with the "ABC method." While it covers the standard-of-care comprehensively, there is room for improvement in discussing the molecular aspects, potential complications, and emerging therapies. With minor revisions, this paper can serve as an essential guide for clinical oncologists in the management of PDAC patients.

Author Response

Recommendations:

• The authors should consider expanding the discussion on the molecular and genetic markers of PDAC, as they play a pivotal role in treatment decision-making.

We dedicated an entire new paragraph on this topic.

• A section dedicated to the potential side effects, complications, and management of the same for each treatment modality would enhance the manuscript's utility for clinicians.

Thank you for this suggestion. We dedicated the entire new chapter for this topic.

• It would be beneficial to include a discussion on emerging therapies, targeted treatments, and ongoing clinical trials in the field of PDAC.

We dedicated a new paragraph on this topic.

• The figures 3 could be better labeled and formatted for clarity.

We corrected labeling.

• Some sections, especially the introduction, could benefit from a more detailed background on PDAC's epidemiology and pathophysiology.

We enlarged the introduction part.

• The authors should consider adding patient case studies or real-world examples to illustrate the application of the "ABC method." Thank you for this suggestion.

Reviewer 4 Report

Comments and Suggestions for Authors

The manuscript provides a comprehensive overview of pancreatic cancer, including its prognosis, staging, and treatment options. It discusses the importance of considering biological and conditional factors in determining resectability. The review highlights the significance of germline BRCA mutations in treatment decisions and addresses specific considerations for rare variants like pancreatic acinar cell carcinoma and adenosquamous carcinoma.

Comments for authors:

Title:

The title accurately reflects the content of the study and is concise and informative.

Abstract:

1.      Even with the limitations of the abstract word wise consider adding a concluding paragraph summarizing the key takeaways from this section and possibly suggesting areas for future research

Introduction:

1.      Provide a brief explanation of CA 19-9 as a tumor marker, including its role in diagnosis and prognosis.

2.      Consider adding a brief section on potential complications associated with pancreatic surgery, as this information is relevant to understanding the challenges of treatment.

3.      Consider incorporating visual aids, such as diagrams or tables, to illustrate the concepts of resectability and the "ABC method." Visual aids can enhance understanding, especially for complex topics.

4.      Provide more specific guidance on maintenance therapy after first-line treatment for metastatic PDAC, including recommended regimens and their benefits. Include references to recent studies or guidelines in this regard.

5.      While the manuscript generally includes citations to support statements, there are instances where specific claims could benefit from more extensive citation of primary research articles and clinical studies. Providing direct references to relevant research will strengthen the manuscript's credibility

6.      While the manuscript is generally well-written, there are minor grammatical and stylistic issues that should be addressed. Careful proofreading and editing are needed to ensure the text is free from errors and maintains a consistent writing style throughout.

7.      Adenosquamous Carcinoma of the Pancreas (ASCP):

8.      The section provides information about ASCP, which is considered more aggressive than typical pancreatic ductal adenocarcinoma (PDAC). It notes that there is no preferred first-line regimen for ASCP based on limited retrospective studies, and both FOLFIRINOX and gemcitabine/nab-paclitaxel have shown efficacy please expand on this where possible

9.      Include the publication years of the cited references to indicate the currency of the sources and their relevance to current clinical practice.

10.   There is no conclusion section

Comments on the Quality of English Language

While the manuscript is generally well-written, there are minor grammatical and stylistic issues that should be addressed. Careful proofreading and editing are needed to ensure the text is free from errors and maintains a consistent writing style throughout.

Author Response

Title:

The title accurately reflects the content of the study and is concise and informative. Thank you!

Abstract:

1. Even with the limitations of the abstract word wise consider adding a concluding paragraph summarizing the key takeaways from this section and possibly suggesting areas for future research

Thank you for this suggestion, we added a concluding paragraph with future directions.

Introduction:

1. Provide a brief explanation of CA 19-9 as a tumor marker, including its role in diagnosis and prognosis. We provided a brief explanation of Ca 19-9 as a diagnostic and prognostic biomarker, see the introduction part.
2. Consider adding a brief section on potential complications associated with pancreatic surgery, as this information is relevant to understanding the challenges of treatment.

Agree! We added the entire chapter dedicated to possible complications/side effects of surgery and systemic treatment. Thanks for this suggestion!

3. Consider incorporating visual aids, such as diagrams or tables, to illustrate the concepts of resectability and the "ABC method." Visual aids can enhance understanding, especially for complex topics.

Figure 1 and Figure 2 aim to give the visual aid.

4. Provide more specific guidance on maintenance therapy after first-line treatment for metastatic PDAC, including recommended regimens and their benefits. Include references to recent studies or guidelines in this regard.

Unfortunately, there are only limited data to guide the management of patients with locally advanced or metastatic pancreatic cancer who achieved disease control after first-line therapy for maintenance therapy. We tried to include all relevant studies and also included them in Figure 2.

5. While the manuscript generally includes citations to support statements, there are instances where specific claims could benefit from more extensive citation of primary research articles and clinical studies. Providing direct references to relevant research will strengthen the manuscript's credibility

We checked this point carefully and added some more references as suggested.

6. While the manuscript is generally well-written, there are minor grammatical and stylistic issues that should be addressed. Careful proofreading and editing are needed to ensure the text is free from errors and maintains a consistent writing style throughout.

We checked carefully the manuscript and corrected it, thank you.

7. Adenosquamous Carcinoma of the Pancreas (ASCP): We expanded this chapter as suggested.
8. The section provides information about ASCP, which is considered more aggressive than typical pancreatic ductal adenocarcinoma (PDAC). It notes that there is no preferred first-line regimen for ASCP based on limited retrospective studies, and both FOLFIRINOX and gemcitabine/nab-paclitaxel have shown efficacy please expand on this where possible. We expanded this chapter as suggested.
9. Include the publication years of thecited references to indicate the currency of the sources and their relevance to current clinical practice. The publication years included.
10. There is no conclusion section

We added conclusion section.