MAGNITUDE OF CA19-9 DECLINE IN RESPONSE TO NEOADJUVANT CHEMORADIATION IS ASSOCIATED WITH OVERALL SURVIVAL IN PATIENTS WITH PANCREATIC CANCER
Sam Thalji*, William Hall, Mohammed Aldakkak, Kathleen Christians, Callisia N. Clarke, Ben George, Mandana Kamgar, Bryan Hunt, Srivats Madhavan, Naveen Kulkarni, Beth A. Erickson, Douglas B. Evans, Susan Tsai
Surgery, Medical College of Wisconsin, Milwaukee, WI
Introduction: Carbohydrate antigen 19-9 (CA19-9) is a valuable biomarker for pancreatic ductal adenocarcinoma (PDAC) and changes in CA19-9 during therapy may inform subsequent clinical decisions. Patients (pts) with borderline resectable (BLR) PDAC often receive systemic chemotherapy followed by localized radiation (XRT). CA19-9 response pattern during XRT, in the absence of systemic therapy, may help identify pts with radiographically occult metastatic disease.
Methods: Pts with BLR PDAC who had an elevated CA19-9 at diagnosis (with a normal bilirubin) and received neoadjuvant chemotherapy followed by XRT were identified. CA19-9 values were classified as normal or elevated (>35 U/mL). CA19-9 levels were examined at diagnosis, following induction chemotherapy prior to XRT (pre-XRT), and following XRT prior to surgery (post-XRT). Proportional change in CA19-9 during XRT was calculated and categorized as a response ('‰¥50% decrease), stable (<10% increase to <50% decrease), or increase ('‰¥10% increase).
Results: Of 180 pts, pre-XRT CA19-9 levels following induction chemotherapy were normal in 42 (23%) pts and remained elevated in 138 (77%). Of 138 pts with an elevated pre-XRT CA19-9, the post-XRT CA19-9 was associated with a CA19-9 response in 74 (54%), stable levels in 28 (20%), and an increase in 36 (26%) pts. Normalization of post-XRT CA19-9 was achieved in 25 (34%) of the 74 responding pts, 2 (7%) of the 28 stable pts, and none of the pts with increasing CA19-9 (p<0.001). Completion of neoadjuvant therapy and surgery was achieved in 59 (79%) of the 74 pts with a response, 16 (57%) of 28 pts with stable CA19-9, and 19 (53%) of 36 pts with an increase in CA19-9 (p=0.01). Metastatic disease was found in 11 (15%) of the 74 pts with CA19-9 response, 10 (35%) of the 28 pts with stable CA19-9, and 11 (31%) of the 36 pts with an increasing CA19-9 (p=0.04). Median overall survival (mOS) was 27 mo in the 74 pts with a response, 16 mo in the 28 pts with stable CA19-9, and 15 mo in the 36 pts with an increase in CA19-9 (p=0.001). There were no differences between pts with stable or increasing CA19-9 levels in terms of treatment completion, rates of metastasis, or mOS. Among the 74 pts who had a CA19-9 response to XRT, the mOS for the 25 pts who normalized their post-XRT CA19-9 was 46 mo, compared to 25 mo for the 49 pts with a response but who did not normalize their post-XRT CA19-9. mOS for the 64 pts with a stable or increasing post-XRT CA19-9 was 16 mo (p<0.001; Figure 1).
Conclusions: During neoadjuvant XRT for PDAC, a '‰¥50% decline in CA19-9 is associated with improved mOS and normalization of CA19-9 levels is associated with the greatest survival advantage. Pts with stable or <50% decline in CA19-9 levels have similarly poor oncologic outcomes to pts with increasing CA19-9 levels, suggesting a high likelihood of radiographically occult metastasis.
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