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Impact of Treatment Sequencing on Sites of First Recurrence in Patients with Localized Pancreatic Cancer
Chad Barnes*1, Mohammed Aldakkak1, Kathleen Christians2, Paul S. Ritch3, Ben George3, Fabian Johnston2, Beth A. Erickson4, Parag Tolat5, W Dennis Foley5, Douglas B. Evans2, Susan Tsai2
1General Surgery, Medical College of Wisconsin, Milwaukee, WI; 2Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI; 3Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI; 4Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI; 5Radiology, Medical College of Wisconsin, Milwaukee, WI
Introduction: Following a potentially curative pancreatectomy for localized pancreatic cancer (PC), metachronous peritoneal metastases occur in up to 20% of patients. We evaluated the impact of neoadjuvant treatment sequencing on the first site of disease recurrence.
Methods: We identified all patients with resectable PC, as defined on pretreatment radiographic imaging, who received either chemotherapy alone or chemoradiation prior to pancreatectomy. Post-treatment disease recurrence was diagnosed on follow-up imaging performed at 3-4 month intervals years 1-2 and at 6 month intervals years 3-5.
Results: We evaluated 91 consecutive patients with resectable PC who received neoadjuvant therapy and surgery; chemoradiation in 61 (67%) patients and chemotherapy alone in 30 (33%). Node positive disease was present in 38 (42%) of 91 patients and positive margins occurred in 3 (3%). Postoperative adjuvant therapy was completed in 37 (60%) of the 61 patients who received neoadjuvant chemoradiation and 22 (73%) of the 30 patients treated with neoadjuvant chemotherapy. Recurrent pancreatic cancer was diagnosed in 38 (42%) of the 91 patients; the first site of disease recurrence was isolated to a single-site in 27 (31%) and multi-site in 11 (12%). The sites of disease recurrence are listed in Table 1. Recurrent disease developed in 28 (45%) of the 61 patients who received neoadjuvant chemoradiation and 10 (33%) of the 30 patients who received neoadjuvant chemotherapy (p=0.25). Single-site peritoneal recurrence was the first site of disease recurrence in 2 (3%) of the 61 patients who received neoadjuvant chemoradiation as compared to 5 (17%) of 30 patients who received neoadjuvant chemotherapy alone (p=0.04). Neoadjuvant chemotherapy (when compared to chemoradiation) was associated with a 6-fold increased odds of developing peritoneal metastases as the first site of disease recurrence (adjusted OR: 6.07, 95%CI: 1.24-29.75, p = 0.03).
Conclusion: Among patients who received neoadjuvant therapy and surgery for resectable PC, there was a trend for decreased recurrence in patients who received full-dose chemotherapy as compared to chemoradiation. However, chemoradiation prior to surgery appeared to reduce the risk of isolated peritoneal recurrence (compared to chemotherapy alone). This data provides additional support for the delivery of all non-surgical therapy first (rather than in an adjuvant setting) for patients with operable PC.
Table 1: Sites of First Disease Recurrence after Neoadjuvant Therapy and Surgery
| | Total
(n=91) | Neoadjuvant
chemotherapy
(n=30) | Neoadjuvant
chemoradiation
(n=61) | p-value | | Single-site, (n,%) | | | Liver only | 11 (12) | 0 (0) | 11 (18) | 0.01 | | Lung only | 8 (9) | 2 (6) | 6 (10) | 1.00 | | Peritoneum only | 7 (8) | 5 (17) | 2 (3) | 0.04 | | Soft tissue only | 1 (1) | 0 (0) | 1 (2) | 1.00 | | Multi-site, (n,%) | 11 (12) | 3 (10) | 8 (13) | 1.00 | | Liver | 9 (10) | 3 (10) | 6 (10) | 1.00 | | Lung | 7 (8) | 1 (3) | 6 (10) | 0.42 | | Peritoneum | 4 (4) | 2 (6) | 2 (3) | 0.60 | | Soft tissue | 3 (3) | 0 (0) | 3 (5) | 0.55 | | Bone | 3 (3) | 0 (0) | 3 (5) | 0.55 |
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