Predictors of Response and Survival in Locally Advanced Adenocarcinoma of the Pancreas Following Neoadjuvant GTX with or Without Radiation Therapy
Authors: Sherman William H. , Hecht Elizabeth , Leung David , Chu Kyung 
Published: December 2017

Lessons Learned
There is no presenting parameter that predicts the success of neoadjuvant therapy for pancreatic cancer. Despite the images on scans following neoadjuvant therapy, all patients should be evaluated, because inflammation following radiation therapy (RT) may overstate the extent of tumor and vascular involvement.

Abstract: Background
In patients presenting with locally advanced pancreatic adenocarcinoma deemed unresectable by two pancreatic cancer surgeons, we analyzed presenting tumor size, extent of vascular involvement, tumor markers, response to neoadjuvant gemcitabine (G), docetaxel (T), and capecitabine (X) with or without additional chemoradiotherapy with GX on R0 resection rates (≥2 mm margins), and survival.

Methods
All patients had baseline magnetic resonance imaging (MRI) and/or computed tomography (CT) scans and endoscopic ultrasound. A baseline positron emission tomography-computed tomography (PET-CT) was performed in 39 patients. The scans were reviewed by two radiologists.
GTX (gemcitabine 750 mg/m2 and docetaxel 30 mg/m2 on days 4 and 11 with capecitabine 1,500 mg/m2 days 1–14) was administered on a 3-week schedule for 6 cycles to patients with both arterial and venous-only involvement. Patients in the arterial arm received GX/RT before surgery, and those in the venous arm received GX/RT after R1 resection. Standard-dose RT was delivered by intensity-modulated radiation therapy (IMRT) or conformal fields to 5040 cGy along with capecitabine for 5 days and gemcitabine on day 5 of weeks 1, 2, 4, and 5 of RT, starting with the first full week of RT.
A cancer antigen test 19-9 (CA 19-9) was obtained at baseline and days 4 and 11 of each cycle. The rate of change in CA 19-9 was calculated using the formula: (Log10 CA 19-9 time 0) − (Log10 CA 19-9 at 9 weeks)/9 weeks. This was derived based on the observation that the fall in CA 19-9 following effective chemotherapy is a second-order function.

Results
Of the 34 patients with arterial involvement and 11 with extensive venous involvement who met the eligibility criteria and began GTX, only 5 patients in the arterial arm did not undergo subsequent resection. The remaining 40 patients were included in this analysis of presenting parameters with respect to R0 resection, disease-free survival (DFS), and overall survival (OS). R0 resection was achieved in 28 of 40 patients (70%), and R1 resection in the remaining 12 (30%). The OS after R0 resection was a median 37 months (95% confidence interval [CI]: 29.3–44.7) compared with 29 months (95% CI: 28.5–41.5) for those with R1 resection.
Excluding four postoperative deaths, median DFS for the 25 (71%) with R0 resection was 31 months (95% CI: 11.3–51.1), and the median DFS for R1 resection was only 14 months (95% CI: 11.1–17). Eleven of the twenty-eight (39%) patients achieving R0 resection have not relapsed (median = 45 months, range = 25–71 months).

Conclusion
R0 resection, the goal of neoadjuvant treatment, can be achieved in 70% of patients presenting with locally advanced pancreatic cancer. The median DFS was 31 months (95% CI: 11. 3–51.1). No relationship was found with tumor size, degree of vascular involvement, carcinoembryonic antigen test (CEA), CA 19-9, degree of tumor regression on scan, fall in CA 19-9, or SUV on PET scan and subsequent survival.