Review for 10.1186/1471-230X-11-123 (2011)

Reviewer's report
Title:Predictive Value of Metabolic 18FDG-PET Response on Outcomes in
Patients with Locally Advanced Pancreatic Carcinoma Treated with Definitive
Concurrent Chemoradiotherapy
Version: 1Date:1 September 2011
Reviewer: Devin Schellenberg
Reviewer's report:
I had the pleasure of reviewing your recent paper regarding the predictive value
of PET in pancreas cancer. We have made little progress in the field of pancreas
cancer so i wish you the best with your continued studies. Below are my
comments regarding the manuscript.
Major Revisions:
1) I belief the most significant issue I have with the manuscript is one that is
difficult to fully address in the setting of pancreas cancer where early progression
is common. The authors use an arbitrary cutoff of SUVmax reduction above
(n=21) and below (n=11) the mean to create 2 comparative groups at the time of
the 12 week follow up scan. In the lesser responsive group 6 of the 11 patients
show local progression by the 12 week scan. The authors are essentially then
comparing a group of non-progressors (n=21) to a group which contains those
that have already progressed (n=6) and a minority (n=5) of patients that have not
progressed. The finding of a difference in local control, progression free and
overall survival is therefore not surprising.
2) Also, the timing of gemcitibine post chemoradiation is not definitively
addressed. How many cycles of gemcitibine did patients receive prior to the 12
week scan? Was there a difference among patients?
3) The change in SUV is deemed significant on multivariate analysis but the
other factors analyzed on multivariate analysis are never mentioned. Did they
include age, sex, original SUV, tumor volume, ECOG, tumor location, stage…?
4) In general I felt that the lengthy references to FDG-PET as a tool for
delineating malignant from benign pancreatic masses, as well as the benefit of
FDG-PET for GTV delineation where tangential to the main thrust of the
manuscript and I feel the 2nd paragraph of the introduction, and the 1st 3
paragraphs of the discussion where off point.
5) The 3rd paragraph of the introduction omits several studies outlining the utility
of PET in predicting clinical outcomes in pancreatic cancer including those by
Lee, SM; Schellenberg, D and Okumato, K, nor does it stress a very similar study
by Choi, M (reference 26) that used a 50% decrease in SUV post chemotherapy
as a cutoff to evaluate prognosis.
6) The stated conclusions were not the focus of this study. For example, other
studies have noted extremely low rates of regional failures in pancreas cancer.
To conclude that FDG-PET-CT reduces geographical misses versus CT alone
without any direct comparison of the two in the current study is misleading.
Minor revisions
1) In the results section of the abstract it is unclear how the groups of greater
versus lesser SUVmax change are defined (this is stated only later in the
manuscript)
2) Background, 1st paragraph, end of second sentence reads
“chemotherapeutics and/or sufficient doses…” perhaps specifying that they are
referring to radiation doses versus chemotherapy doses with “chemotherapeutics
and/or sufficient RADIATION doses…”
3) Background, 2nd paragraph, end of 1st sentence…”and systemic extend of
disease in tumor sites…” I think it should read “and systemic extend of disease in
MANY tumor sites” or “SEVERAL tumor sites”…
4) Results, 1st paragraph, ~7th sentence “Sixteen patients developed in field
recurrences, 3 of which were isolated and 13 were distant relapses” should be
changed to “Sixteen patients developed in field recurrences, 3 of which were
isolated and 13 were CONCOMITANT WITH distant relapses”
5) Discussion, 4th paragraph. I disagree with the sentence “Gemcitabine, with its
strong radiosensitizing properties, is promising, but its utility remains to be
investigated.” Studies by Brade, Murphy and others have combined gemcitibine
with radiation effectively.
6) In table 1 and 2 the Y axis is “Survival (%)” but the demarcations of the Y axis
are 0,2 to 1,0 (the 0,8 demarcation is missing the comma). These should be
changed to 20-100 to be concordant with the (%) symbol.
Discretionary revisions
1) Emphasizing how SUVmax changes effect prognosis could be accomplished
by reporting the differences in overall survival between “responders and
non-responders” groups differentiated by the median SUVmax change or a strict
50% reduction in SUVmax as Choi et al. report. This might at strength to the
authors’ conclusions.
2) The median SUVmax seems high versus previous pancreas studies. I’m not
sure this needs to be addressed but could be compared with other studies.
3) Why was the 12 weeks post CRT chosen as the time to evaluate response?
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests