Change in CA 19-9 Levels after Chemoradiotherapy Predicts Survival in Patients with Locally Advanced Unresectable Pancreatic Cancer

Abstract

.Purpose: RTOG 9704 demonstrated a prognostic role for postoperative CA 19-9 in patients with resectable pancreatic carcinoma following surgery. Our study aimed to investigate whether CA 19-9 provided similar prognostic information in patients with locally advanced unresectable pancreatic cancer (LAPC) treated with chemoradiotherapy (CRT) and to determine whether such endpoints should therefore be reported in future randomized trials. Only patients with a bilirubin of less than 2 mg/dL at the time the CA 19-9 was evaluated were included in the analysis to avoid the confounding effect of hyperbilirubinemia. Of the eligible patients, 54 had pre and post CRT CA 19-9 values available. The median age was 68 years and 52% were female. Categorized versions of the first post-CRT CA 19-9 were tested in 50 point increments beginning at <50 to >1,000 and percent change in pre to post-CRT CA 19-9 using cut points of 10% increments from <0% (increased) to >90%. Survival was measured from the date of first post CRT CA 19-9 level until death or last follow-up.Univariate and multivariate statistical methodologies were used to determine significant prognostic factors for overall survival.Results: Median CA 19-9 prior to CRT was 363 U/mL and post CRT median was 85.5 U/mL. Following CRT, patients with a decrease of >90% from their baseline CA 19-9 level had a significantly improved median survival than those that did not (16.2 vs. 7.5 months, P=0.01). The median survival of patients with a CA 19-9 level lower than the median post CRT value was 10.3 months, compared with 7.1 months for those with a CA 19-9 level greater than the median (P=0.03). Post CRT CA 19-9 less than 50 U/mL and histologic grade I-II also showed prognostic significance (both P=0.03). In multivariate analysis, post CRT CA 19-9 less than the median level of 85.5 U/mL was an independent prognostic factor for overall survival (HR 0.34; 95% CI, 0.13-0.85, P=0.02). Conclusions:Our results indicate that post treatment CA 19-9 is predictive for overall survival in patient with LAPC following CRT. We recommend that pre and post treatment CA 19-9 levels be obtained in patients receiving CRT and that these values be considered for prognostic nomograms and future clinical trials.

Outcome Analysis of Chemoradiation in Unresectable Pancreatic Cancer Focusing on Treatment Sequencing Strategy

“…This wide range of accrual is somewhat reflected in various chemotherapy regimens employed. Also, CA 19-9 values, known to be important prognostic factor (23,26), were unavailable for more than one-third of the patients, especially those treated in earlier period, which may have impacted current prognosticator analysis.…”

Mechanisms of cisplatin resistance and targeting of cancer stem cells: Adding glycosylation to the equation

“…Yet, the contribution of these events to chemotherapy resistance remains to be determined. Adding to these findings, several studies associated elevation of serum sTn antigen (detected by the CA72-4 test) and sLe a (detected by the CA19-9 test) levels in cancer patients with both recurrence after chemotherapy, metastasis and poor overall survival (Kim DH et al, 2015;Yang GY et al, 2013;Ziske C et al, 2003), suggesting that the presence of these glycans may be associated with drug resistance. However, this hypothesis warrants confirmation in future studies.…”

“…In particular, several reports associate the overexpression of sLe a with decreased overall survival in digestive tract tumors (Kannagi R, 2007;Matsui T et al, 2004;Portela SV et al, 2011). Furthermore, serological detection of sLe a on glycolipids and glycoproteins by the CA19-9 assay is used as a diagnostic tool to monitor clinical response to therapy for these tumors (Humphris JL et al, 2012;Kannagi R, 2007;Yang GY et al, 2013). Furthermore, the 2,6-oversialylation of lactosamine chains and overfucosylation of terminal motifs are also among some of the commonly observed structural alterations present in cancer cells (Christiansen MN et al, 2014).…”

Cancer Antigen 72-4 for the Monitoring of Advanced Tumors of the Gastrointestinal Tract, Lung, Breast and Ovaries

“…For example, patients with a CA19-9 level greater than 1,000 U/ml at time of diagnosis were more likely to have unresectable disease (40). Biomarker analysis in large phase 3 pancreatic cancer trials showed that a decrease in CA19-9 by at least 90% correlated with increased survival (41)(42)(43). Prognostication studies by Reni et al showed that the basal value of CA19-9 in advanced pancreatic disease correlated with survival (44,45).…”