Nomogram for Predicting Distant Metastasis of Pancreatic Ductal Adenocarcinoma: A SEER-Based Population Study
Round 1
Reviewer 1 Report
In this paper the authors describe a nomogram to define the percentage of distant metastases in PDCA. I think this is an interesting methods even if it groups well known and described variables related to a worst prognosis of PDCA. If possible I would describe more extensively the limitations of the study especially how neo adjuvant chemotherapy could change these results.
Globally I recommend it for publication
Author Response
Dear Reviewers,
On behalf of my co-authors, we thank you very much for giving us an opportunity to revise our manuscript, and we also appreciate you very much for your positive and constructive comments and suggestions on our manuscript entitled “Nomogram for predicting distant metastasis of pancreatic ductal adenocarcinoma: a SEER-based population study”.
We have studied your comments carefully and have revised our manuscript. Attached please find the revised version and document, which we would like to submit for your kind consideration.
The following are responses to your comments:
Comment 1: In this paper the authors describe a nomogram to define the percentage of distant metastases in PDCA. I think this is an interesting method even if it groups well known and described variables related to a worst prognosis of PDCA. If possible I would describe more extensively the limitations of the study especially how neo adjuvant chemotherapy could change these results.
Response 1: Your suggestion is greatly appreciated. We have given additional descriptions of the limitations, including " how neoadjuvant chemotherapy changes these results", as detailed in lines 317-322.
Reviewer 2 Report
The authors have gone out to determine what are the factors that lead to distance metastatic disease in pancreatic cancer. It is well know that distant mets leads to a poor outcome. The thought of being able to identify the potential of someone to have distant mets may affect clinical decision making. This is a well written manuscript
Some questions I have:
1. It would be good to discuss why its important to know if someone has a risk of distant mets versus local mets. How does the treatment change, if any? If knowing someone has the potential for a distant met, would this mean you need to be more aggressive with treatment? I think this is fundamentally missing from your manuscript and should be addressed.
2. Using ICD codes with stating what they individually are, makes it difficult for the reader to pick out what is being included or not. I assume ampullary, pNETs, and pancreatic CA of different path types were excluded, but hard to tell with out doing a search of the ICD codes to verify thing. It would be nice to list what each one means for the reader.
3. Why 2010-2015? I am sure there is a justification, but I could not find it.
4. Newer treatments like gemcitabine + Nab-paclitaxel was probably not available until 2012/2013. its better tolerability has allowed older patients to be treated (when compared to FOLFIRINOX). Since treatment would affect outcomes, I would be curious if you expanded the cohort to 2016 or 2017 what the affects of age would be on outcomes. This might be out of the scope of what could be analyzed for this manuscript but I would not mind somewhere addressing the role of treatment on your data.
4: RE age. Is the rate for distant metastases occurring over the age of 80 a result of a patient not living long enough to get a distant met? As well, we would expect those over 80 to have a worse OS than those under 60, as there is more a likelihood that those over 80 were given less systemic treatment than <60 which would affect survival I would imagine. Was this accounted for in the model? if not then minimally it should be in the discussion.
5. With race, what role does the fact that only just about 10% of the sample size is black while around 75% is caucasian? Can you truly draw any comparisons when the sample size differs so much? Maybe african americans only sought treatment or had access to treatment when they were much sicker, so thus more of a chance of distant mets? I am wondering if you could comment on this?
Note there were a couple of minor grammer errors such as "fourth leading cause of cancer death" on line 39 should probably read fourth leading cause of cancer-related deaths.
Author Response
Dear Reviewer2,
On behalf of my co-authors, we thank you very much for giving us an opportunity to revise our manuscript, and we also appreciate you very much for your positive and constructive comments and suggestions on our manuscript entitled “Nomogram for predicting distant metastasis of pancreatic ductal adenocarcinoma: a SEER-based population study”.
We have studied your comments carefully and have revised our manuscript. Attached please find the revised version and document, which we would like to submit for your kind consideration.
The following are responses to your comments:
Comment 1: It would be good to discuss why its important to know if someone has a risk of distant mets versus local mets. How does the treatment change, if any? If knowing someone has the potential for a distant met, would this mean you need to be more aggressive with treatment? I think this is fundamentally missing from your manuscript and should be addressed.
Response 1: Thank you for your comments. We have given the importance of predicting the probability of distant metastasis risk in the discussion section (in lines 217-219).
Comment 2: Using ICD codes with stating what they individually are, makes it difficult for the reader to pick out what is being included or not. I assume ampullary, pNETs, and pancreatic CA of different path types were excluded, but hard to tell without doing a search of the ICD codes to verify thing. It would be nice to list what each one means for the reader.
Response 2: Thank you very much for your suggestion. We have given the meaning of the ICD codes involved in the study. We have made the appropriate changes in the manuscript in lines 68-72.
8140: Adenocarcinoma, 8500: infiltrating duct carcinoma.
C25.0: Head of pancreas, C25.1: Body of pancreas, C25.2: Tail of pancreas, C25.3: Pancreatic duct, C25.4: Islets of Langerhans, C25.7: Other specified parts of pancreas, C25.8: Overlapping lesion of pancreas, C25.9: Pancreas.
Comment 3: Why 2010-2015? I am sure there is a justification, but I could not find it.
Comment 4: Newer treatments like gemcitabine + Nab-paclitaxel was probably not available until 2012/2013. its better tolerability has allowed older patients to be treated (when compared to FOLFIRINOX). Since treatment would affect outcomes, I would be curious if you expanded the cohort to 2016 or 2017 what the affects of age would be on outcomes. This might be out of the scope of what could be analyzed for this manuscript but I would not mind somewhere addressing the role of treatment on your data.
Response 3 and 4: Thank you very much for your comments. Based on comments 3 and 4, we provide the following explanation. Because information on distant metastases was not registered in this database until 2010, the AJCC 7th edition TNM staging was included between 2010-2015, and information on tumor size was only collected between 2004-2015. The final extracted data need to satisfy the above conditions, so the pooled time is 2010-2015. If the study cohort is expanded to 2016 or 2017, we will not be able to extract valid data from the database. We are very sorry for this.
Comment 4 RE age: Is the rate for distant metastases occurring over the age of 80 a result of a patient not living long enough to get a distant met? As well, we would expect those over 80 to have a worse OS than those under 60, as there is more a likelihood that those over 80 were given less systemic treatment than <60 which would affect survival I would imagine. Was this accounted for in the model? if not then minimally it should be in the discussion.
Response 4 RE age: Your suggestions have been very helpful to us. We have added a discussion of "The potential causes perhaps were younger patients usually have a more positive attitude toward therapies and have better physical condition to tolerant various treatment modalities. However, this study did not consider whether the elder patients received less systemic therapy than the younger patients. In addition, since elderly PDAC patients are in poorer physical condition, the probability of non-neoplastic death is higher, resulting in shorter survival and thus not enough time for distant metastases to occur, which is also a possible factor contributing to the low risk of distant metastases in elderly patients. Therefore, clinicians should pay special attention to whether patients under 60 years of age are at high risk of distant metastases, which may affect their prognosis." in lines 241-252 of the manuscript.
Comment 5: With race, what role does the fact that only just about 10% of the sample size is black while around 75% is caucasian? Can you truly draw any comparisons when the sample size differs so much? Maybe african americans only sought treatment or had access to treatment when they were much sicker, so thus more of a chance of distant mets? I am wondering if you could comment on this?
Response 5: We strongly agree with you. Blacks are a vulnerable group in the United States and they may have very limited access to medical interventions. We speculate that most black patients are likely to have developed distant metastases by the time receiving treatment. Even so, race as a baseline characteristic should have been included in the study. Although the sample size of blacks in this study was significantly underrepresented relative to whites, multivariate analysis did not show that race was statistically significant.
Relevant grammatical errors have been corrected in the manuscript.
Once again, thank you very much for your comments and suggestions. We hope that the corrections will meet with approval. If you have any questions, please do not hesitate to contact us.
Yours sincerely,
Wei-Bo Li
Round 2
Reviewer 2 Report
The authors have sufficiently answered all of my questions and have made the appropriate changes to the manuscript.
Thank you
