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Do Women Respond More Favorably Than Men to the FOLFIRINOX Regimen in Advanced Pancreatic Cancer ?

We have come across an interesting recent finding from researchers in Austria.

Greil and colleagues from the Paracelsus Medical University in Salzburg, have published the results of their work in the January 2014 issue of the International Journal of Oncology. These findings appear to suggest that the female gender may be a predictor of a positive response to the four-drug regimen known as FOLFIRINOX in the treatment of advanced pancreatic cancer (ductal adenocarcinoma of the pancreas).

The researchers undertook a retrospective analysis of 49 patients with unresectable cancer of the pancreas who were treated with FOLFIRINOX.  This included 24 females and 25 males. Although the overall median survival duration of women in this study was not found to be significantly different than the men (15 months vs. 12 months) the women’s progression-free survival, response rates and disease control rates in pancreatic cancer were significantly improved over their male counterparts.  This was a surprising finding.

The demographics of the females appeared fairly well matched compared that of the males, although the women showed higher levels of CA 19-9, CEA, Ki-67 and mutated p53 cells.  Also perhaps significantly, the women demonstrated more stage 3 tumors and many less stage 4 then the men.   Finally, the authors point to the increased number of non-metastatic locally advanced tumors in the male patients versus the females (6 vs. 0) with the idea that these may have nullified the advantage conferred by women having a higher response rate.

Still, this is an intriguing result worthy of further inquiry.

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Dale O’Brien, MD

Is CA125 a Better Marker than CA 19-9 for Resectability in Pancreatic Cancer ?

Color this finding: curious (and consequently interesting).

Chinese researchers in Shanghai including Yu and colleagues at Fudan University published recent research findings in the December 2013 issue of the Journal of Gastrointestinal Surgery, the official periodical of the Society for Surgery of the Alimentary Tract.  They reviewed the results of a number of potential serum tumor markers in 212 patients with confirmed pancreatic cancer (ductal adenocarcinoma of the pancreas).

The aim of the work was to establish which marker could be of best use in predicting which patients were found at an early enough stage of pancreatic cancer to be potentially eligible for surgery.  The markers under study included alpha-fetoprotein (AFP), carcinoembryonic antigen CEA), CA19-9, CA50, CA125, CA242, and CA724.

Based on past work one might have predicted the superior marker to be CA 19-9. But in fact, CA125 (often elevated in ovarian cancer) proved superior for this specific task. The selected cut-off value was 19/7 U/mL, which gave a respectable Receiver Operating Characteristic (ROC) area of 0.81.  (The ROC area of CA 19-9 with a cut-off of 289.4 U/mL was only 0.66).

We are not sure where to go with this result.  But a first step would be to substantiate it.  One might imagine that perhaps as a part of a panel – this could potentially be useful.   It would be interesting to see how CA125 tracks with early and advanced stages of pancreatic cancer.

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Dale O’Brien, MD


Salivary Fluid Markers for Pancreatic Cancer: the evidence mounts

However counterintuitive, the association between saliva and the dental environment AND pancreatic cancer (ductal adenocarcinoma of the pancreas) continues to garner highly interesting research.  One team lead by David T. Wong and colleagues at the Dental Research Institute of the UCLA School of Dentistry in Los Angeles, California first came to our attention per the Pancreatica blog on 6/23 of this year for a 2010 article in the journal Gastroenterology laying the basis for salivary biomarkers for cancer of the pancreas, and later for a 2012 article in the journal Gut postulating specific oral bacteria as associated with pancreatic cancer.

This UCLA team has now published an article in the September 13, 2013 issue of the Journal of Biological Chemistry that lays an intriguing and perhaps even likely possible predicate for the mechanism by which salivary fluid may be specifically affected by such apparently distal and unrelated diseases such as pancreatic cancer.

Before presenting the results of their research, we should discuss the concept of exosomes.  Identified in the late 1980s, these are tiny (30 to 100 nanometers in diameter) durable vesicles or bubble-like structures that are found in most biological fluids. They have been found to contain proteins and other substances including messenger-RNA. In an over-simplistic statement, these structures appear to facilitate or at least affect such processes such as cell-to-cell communication throughout the body, coagulation, waste management, tumor invasion, and the immune response. The origin of exosomes is from within cells – and then in some cases, the plasma cell wall releases an exosome to extracellular space within which it can travel.

Wong and his fellow researchers in this present work, studied the role of exosomes that derived from pancreatic cancer tissue – and evaluated their presence and possible function in saliva in a mouse model.  They developed a mouse that gave specific biomarkers for pancreatic cancer by implanting a pancreatic cancer cell line into the animal’s pancreas – and then identifying a selective panel of biomarkers and thereupon testing for these markers in the saliva of those mice with pancreatic cancer (which were found) as compared to those without (not found). Almost all of the components of this panel of seven gene-derived transcriptomic biomarkers were found in the affected mice tumor, serum, saliva, and exosomes.

Then the researchers used a modified tumor line that tended to suppress exosome production from the pancreatic cancer tissue.  They then again looked at these mice tissues and found that almost none of the components of the seven biomarker panel were found in the saliva of these affected mice.  This allowed the researchers to cautiously postulate a working theory that tumor-derived exosomes may be central to the pathway that establishes salivary biomarkers that appear to be specific for (in this case) pancreatic cancer. The authors call for further research to more fully explicate the precise course of the pathways in this process.

And we could ask for nothing more as a follow-on to this growing body of evidence from this clearly talented research team.

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Dale O’Brien, MD


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