Download RESPONSE TO REVIEWERS

RESPONSE TO REVIEWERS
This is an interesting population based paper on the impact on survival of pancreatic cancer resection.
However I have some concerns that I would like to be addressed by the authors.
1. I am aware of the fact that the role of radiotherapy is still controversial in pancreas cancer treatment
in neoadjuvant setting! I understand that, despite the evidence, in USA is current practise. On the
contrary, chemotherapy has been proved beneficial in many studies and in metaanalysis! I am surprised
that tere is no reference on the use of adjuvant chemotherapy.
Response: We thank the reviewer for his insightful comment. We have added references to the
chemotherapy of pancreatic cancer. A detailed discussion of chemotherapy is out of scope of the
present article and hence discussion was limited to a brief summary of the current role of
chemotherapy for treatment of pancreatic cancer
2. I have also concerns that the resection margins are not reported. This could have a significant impact
on survival comparisons between resected and non - resected patients as R2 resect6ions has almost
identical survival with those patients received no operation.
Response: The reviewer has made an excellent comment. However, the data available in the SEER
database does not provide us with that information. We apologize for the lack of data but this is an
inadvertent weakness of the study which we cannot rectify.
3. I dissagree with the last statment in the paper that " Until newer
targeted therapies become available, it is hoped that optimum selection of patients for surgical
resection will offer an effective therapeutic (although not always curative) option for these patients."
Resection will be the cornerstone of ANY future adjuvant therapy, including molecular based
treatments.
Response: We agree with the reviewer that surgery will remain the key treatment for pancreatic
cancer. We have modified the statement in the revised version of the manuscript accordingly.
4. There are some typing errors that should be corrected (e.g. page 2 line 9 "surgery " instead of
"survival".
Response: Thank you for catching the error. We have corrected the error in the revised version.
-----------------------------------------------------Reviewer B:
This is an interesting paper that investigates the role of surgery in patients without vascular invasion.
• A major issue to be addressed is why the patients who had probably resectable pancreatic cancer did
not undergo surgery. Probably these patients were excluded from surgery due to other underlying
conditions, co-morbidity, or preference of the physician and/or the patient for conservative palliative
treatment. This is a major limitation of the study, because it probable shows that patients who were not
operated were probably in poorer general medical status than patients who did. At least, this issue
should be commented by the authors as a limitation of the study.
Response: We thank the reviewer for his insightful comment. Indeed, we asked ourselves the same
question. There are several possibilities including patient refusing surgery. The SEER database is
limited in that aspect in that it does not allow us to identify the reason why some patients who should
have received surgery did not undergo the procedure. We have included a statement in the revised
manuscript that acknowledges this limitation of the current study.
• There is no information about the role of neoadjuvant or adjuvant chemotherapy on survival. Patients
who are operated with a pancreatic malignancy and have a poorly or moderately differentiated tumor
usually receive chemotherapy and the same may be true for patients who prefer non-surgical
treatment. So it would be of great value if the authors could add this information on the paper and
include it in the statistical analysis.
• In any surgical treatment of cancer, one of the factors examined is whether the resection margins
were clear. In addition, it is common in pancreatic cancer patients to have a theoretically resectable
disease before surgery that is proven to be unresectable after surgery. Could we have any information
regarding this issue (if this is not possible to be retrieved by the database, at least comment on that as a
major factor that could lead to poor outcome after surgery).
Response: The SEER database that was queried does not provide information on chemotherapy. We
plan to use this data to request for access to the SEER Medicare Linked database which has data on
chemotherapy as well. We hope to address the excellent question raised by the reviewer in a
subsequent manuscript.
• It is rather easy to guess in any case of cancer that surgical resection of the primary tumor in patients
with no evidence of metastatic disease or vascular invasion improves survival. By these means, the aim
of the paper is by definition proven. However, some of the information provided is useful (about
characteristics of the patients, factors that could influence the decision to operate or not a patient and
factors that could affect survival in pancreatic cancer). I would propose changing the title to “Factors
that influence the decision for surgery and the overall survival in patients with theoretically resectable
pancreatic cancer” or something like that. It is less aggressive and probably more challenging for the
reader. But still it is a decision of the authors if they want to change the title or not for their work.
Response: We welcome the excellent suggestion by the reviewer. We think it would certainly be a
good idea to alter the title to reflect the factors that we found influenced the decision to undergo
surgery in patients with resectable pancreatic cancer. We have revised the title in the revised version
of the manuscript.
• Typo in page 2, line 9: undergo surgery.
Response: We corrected the mistake in the revised version
• Figure 1: I see four lines on the index but only two lines on the graph in my computer. Could you
please check and correct if there is any mistake?
Response: We have checked the results. I believe what the reviewer is referring to the 2 instead of the
4 lines are the cross hairs that represent cases that were censored. So, there are in fact only two lines
on the graph, one for those who did and one for those who did not undergo surgery. The cross hairs
are the censored cases, so there is one for each of the aforementioned two groups.
• Did any of the patients undergo endoscopic ultrasound for staging before surgery? Do we have this
piece of information?
Response: While we asked the same question we do not have that information in our currently
available data.