This is a very interesting topic.. however i think we need to clarify whether we are talking about potentially resectable or borderline/irresectable tumors since the intent of neoadjuvant will change for both scenarios..

although i'm unaware of the evidence, my impression is that neoadjuvant therapy may be beneficial for certain group of patients that we cannot accurately predict preoperatively.. these include patients who are found to have unresectable disease on exploration, patients who have occult metastasis and patients who do not do well despite an R0 resection.

i look forward to comments from experts and their experiences in this matter..

regards, raza

That is a really hot topic Chi. There is data showing that neoadjuvant chemo definitely has a place in the treatment plan. However the indications are not still so clear. All the studies are consistent that there is a benefit for the pts with “borderline” resectable pancreatic cancer. Some studies find a benefit for initially resectable pts too in terms of higher R0 resection rate, but other studies do not confirm that. Also the chemo/CRT combinations vary widely and it is difficult to compare directly current studies. Look at some meta-analyses:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857873/pdf/pmed.1000267.pdf

http://link.springer.com/article/10.1245%2Fs10434-011-2110-8

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164966/pdf/nihms317019.pdf

There are 20 or more ongoing trials on the subject, and I am interested very much of gemcytabine+abraxane trials, as the response rates in previously reported studies with this combination are really impressive.

http://clinicaltrialsfeeds.org/clinical-trials/results/term=NEOADJUVANT+GEMCITABINE+AND+ABRAXANE+CHEMOTHERAPY

Thanks much for both responses.

Thanks for articles, Alexander! They are very useful!

There are different populations here.

1) For patients with the upfront resectable disease, we are hoping that neoadjuvant therapy will improve survival, if not, then the reason to do neoadjuvant therapy becomes vague. The argument can be that patients may not be able to tolerate postoperative adjuvant therapy but they usually can tolerate neoadjuvnat therapy without problems.

2) For patients with borderline resectable disease, we are hoping to down stage them and turn them into resectable, therefore to improve their survival. For these population, we don't know what regiment will be the best, chemotherapy or chemoradiation therapy? May be Gemcitabine+Abraxane? We don't know yet. May be hypofractionated stereotactic radiation therapy will be helpful?

3) for patients with unresectable disease, the chances that neoadjuvant therapy turns them into resectable is slim. So, it becomes definitive therapy. The question becomes if radiation is beneficial or not?

Chi

Here are two interesting papers on the subject of nab-paclitaxel and pancreatic cancer stroma that correlates to the discussion

http://www.cancertreatmentreviews.com/article/S0305-7372(13)00089-3/abstract, http://www.nature.com/bjc/journal/v109/n4/abs/bjc2013415a.html

Thank you!

More importantly, a Phase III study showed that nab-paclitaxel plus gemcitabine significantly improved overall survival (HR 0.72) and progression-free survival (HR 0.69) versus gemcitabine alone for the first-line treatment of patients with metastatic pancreatic cancer.

Dear Chi,

here I think we should discriminate different stage of PC

1) In primary resectable (that in my opinion include also patients with limited vein involvement), I think there are no evidence of use of NA treatment. The reason to support my idea are the following:

- We have not an efficient treatment. We know that only about 15-20% of our patients will respond to the treatment, that means that the remaining 80% will progress

- Before a neo adjuvant treatment we need a biopsy and a stenting (in mostly of the cases). That increase the risk of complication like acute pancreatitis and then for some patients the impossibility to do the NA treatment and maybe to be operated.

2) In locally advanced PC, with arterial involvement, considering the bad results of an "up-front" surgery, I think NA treatment can be used to select the patient for a surgical program.

Hi completely agree with you. In selected patients with LAPC downstaging is probably worth an effort but for resectable patients, considering the available treatment options, it is not a clinical reality. However, it should be tested in clinical trials, which it is