Longer Course of Induction Chemotherapy Followed by Chemoradiation Favors Better Survival Outcomes for Patients With Locally Advanced Pancreatic Cancer

Abstract

Objectives: At diagnosis, 30% of patients with pancreatic cancer are unresectable stage 3 locally advanced. The standard treatment for locally advanced pancreatic cancer (LAPC) is not defined. The current study was conducted to assess the roles of chemotherapy and chemoradiation for LAPC treatment.

Materials and methods: Between June 2006 and March 2011, 100 patients with LAPC were treated at the Johns Hopkins Hospital. Retrospective analysis was performed to compare cumulative incidence of progression (CIP) and overall survival (OS) among different subgroups.

Results: For the 100 patients, the median OS was 15.8 months and the median CIP was 8.4 months. The combination of chemotherapy and chemoradiation before disease progression was significantly associated with improved CIP (P=0.001) and improved OS when compared with chemoradiation alone (median OS: 16.4 vs. 11.1 mo, P=0.03). Among patients receiving combination treatment, patients who received chemotherapy first followed by chemoradiation had a trend toward lower CIP (P=0.09) and improved OS (median OS: 18.1 vs. 11.0 mo, P=0.09). Patients who received >2 cycles of chemotherapy before chemoradiation had a significantly decreased CIP (P=0.008) and a trend toward better OS (median OS: 19.4 vs. 15.7 mo, P=0.10). On multivariate analysis, receiving >2 cycles of chemotherapy before chemoradiation was associated with improved CIP.

Conclusions: Although combination chemotherapy and chemoradiation is favored in the treatment of LAPC, longer induction chemotherapy may play a more important role in sensitization of tumors to subsequent chemoradiation. Our results support treating patients with induction chemotherapy for at least 3 cycles followed by consolidative chemoradiation. These results merit further validation by a prospective study.

Figure 1. Plots of cumulative incidence of progression and Kaplan-Meier curve of overall survival

A. Median CIP was 8.4 months. B. Median OS was 15.8 months. (CIP indicates cumulative incidence of progression; OS, overall survival)

Figure 2. Plots of cumulative incidence of progression and Kaplan-Meier curve of overall survival by therapeutic types: combination therapy vs. chemoradiation alone, or vs. chemotherapy alone

A. Patients who received combination therapy had a significantly better CIP compared to patients who received chemoradiation alone (median CIP, 11.7 vs. 2.2 mo, p=0.001). B. Patients who received combination therapy had a significantly better OS compared to patients receiving chemoradiation alone (16.4 vs. 11.1 mo, p=0.03). C. There was no difference in CIP between patients receiving combination therapy and patients receiving chemotherapy alone (11.7 vs. 4.5 mo, p=0.15). D. There was also no difference in OS between patients receiving combination therapy and patients receiving chemotherapy alone (16.4 vs. 15.9 mo, p=0.55). (CIP indicates cumulative incidence of progression; OS, overall survival)

Figure 3. Plots of cumulative incidence of progression and Kaplan-Meier curve of overall survival by sequence of chemotherapy or chemoradiation therapy within patients who underwent combination therapy

A. Patients who received chemotherapy first followed by chemoradiation had a trend towards improved CIP compared to those who received chemoradiation first followed by chemotherapy (12.6 vs. 8.3 mo, p=0.09). B. Patients who received chemotherapy first also had a trend towards improved OS outcomes compared to those who received chemoradiation first (18.1 vs. 11.0 mo, p=0.09). (CIP indicates cumulative incidence of progression; OS, overall survival; chemotherapy first/Chem first, chemotherapy followed by chemoradiation; chemoradiation first/chemrad first, chemoradiation first followed by chemotherapy)

Figure 4. Plots of cumulative incidence of progression and Kaplan-Meier curve of overall survival by cycles of chemotherapy received before radiation

A. Patients who received >2 cycles of chemotherapy prior to chemoradiation had a significantly better CIP compared to those who received ≤2 cycles of induction chemotherapy (15.0 vs. 8.2 mo, p=0.008). B. Patients who received >2 cycles of chemotherapy prior to chemoradiation had a trend towards better OS compared to patients receiving ≤2 cycles of induction chemotherapy (19.4 vs. 15.7 mo, p=0.10). (CIP indicates cumulative incidence of progression; OS, overall survival; cycle ≤2, 0–2 cycles of induction chemotherapy prior to chemoradiation; cycle >2, >2 cycles of induction chemotherapy prior to chemoradiation)