A miRNA signature linked to local-regional failure and overall survival after pancreatic cancer resection

The cover for issue 10 of Oncotarget features Figure 3, "Overall survival (OS) for high (red) versus low (black) risk groups in the (A) OSU, (B) TCGA, and (C) SNU resected cohorts," by Wolfe, et al.

Digital mi RNA expression profiling was performed and risk scores were calculated based on the expression levels of the four most significantly correlated mi RNAs and dichotomized about the median to detect correlations between risk group, LRR and overall survival.

On multivariable analysis, the risk score remained significantly associated with LRR.

They have developed a 4-mi RNA molecular signature that is associated with risk of LRR and OS after PC resection and validated on two separate cohorts.

Dr. Terence M. Williams from The Ohio State University Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, OH, USA said:

In the United States, there are an estimated 56,770 new cases of pancreatic carcinoma (PC) and 45,750 estimated deaths."

Interestingly, a National Cancer Database study and retrospective studies from Mayo Clinic and Johns Hopkins have reported superior local-regional control and OS in patients receiving adjuvant chemoradiation versus observation or chemotherapy alone.

The ongoing phase III RTOG 0848, a randomized trial between adjuvant CRT versus chemotherapy alone should provide more clarity on whether adjuvant chemoradiation can improve outcomes.

Past efforts have focused on using clinical and pathologic features to predict patterns of failure and prognosis after surgery, in hopes that improved patient selection for adjuvant therapy may improve outcomes.

To that end, the researchers carefully characterized patterns of recurrence in patients treated with surgery and postoperative chemotherapy alone at our institution using patterns of failure radiologic analysis.

Their aim is to identify a mi RNA expression profile that correlates with LRR and OS after surgical resection which might be used to better select patients who could benefit most from adjuvant chemoradiation in the future.

The Williams Research Team concluded, in their Oncotarget Research Article:

We have developed a four miRNA risk score that provides prognostic information for clinical outcomes after surgical resection for pancreatic cancer. Based on the ability of our four miRNA risk score to predict local-regional control, as well as overall survival in three cohorts, such molecular profiles have the potential to help guide clinical decision-making for pancreatic cancer patients after surgical resection. We further intend to apply our risk stratification miRNA score to patients treated on prospective clinical trials with surgery followed by chemotherapy with and without chemoradiation to validate its ability to predict LRR and OS. In addition, this risk score warrants testing on patients who have received neoadjuvant (preoperative) chemotherapy for locally-advanced or borderline resectable PC in order to determine if this miRNA signature can risk-stratify patients in the neoadjuvant setting who would benefit from escalated local-regional therapy (such as radiation or chemoradiation). Such a risk score in the neoadjuvant setting could help decide the need to employ radiation therapy to improve margin negative resection rates and lymph node clearance rates, thereby likely improving local-regional recurrence. Thus, we feel that further validation studies with larger patient numbers and with rigorous patterns of failure data are warranted."