Department of Surgery, University of Pittsburgh, Pittsburgh, PA
Asmita Chopra , Jacob C. Hodges , Adam Olson , Steven A. Burton , Kenneth K. Lee , Nathan Bahary , Aatur D. Singhi , Brian A. Boone , Michael T. Lotze , Melissa E. Hogg , Herbert Zeh III, Amer H. Zureikat
Background: Neoadjuvant therapy is increasingly used for pancreatic cancer (PDA). The comparative efficacy of neoadjuvant chemotherapy (NC) versus chemoradiation (NCRT) remains uncertain. We aimed to compare NC and NCRT on survival outcomes and pathologic endpoints of PDA. Methods: Single-center analysis of PDAs treated with NC or NCRT between 2008-2018. Average treatment effects (ATE) were estimated after matching cases to controls using Mahalanobis distance nearest-neighbor matching. Competing risk survival analysis and inverse probability weighted estimates (IPWE) were used for disease free survival (DFS) and overall survival (OS) respectively. Results: Of 418 patients (median age 67yrs, 51% females), 327 received NC and 91 received NCRT. NCRT patients had more locally advanced disease, cross-over NC regimens (gemcitabine & 5-FU based), longer neoadjuvant therapy duration, open surgery and vascular resection (all p < 0.05). NCRT was associated with lower LN positivity, LNR, LVI and PNI, higher R0 rates, and higher near complete and complete pathologic responses (all p < 0.05, table). After adjustment, NCRT was associated with a significant reduction in LN positivity [95%CI = (-)0.41-(-)0.07; p = 0.007] and LVI [95%CI = (-)0.36-(-)0.03; p = 0.02]. While NCRT was associated with improved OS on UVA (25.5 vs. 21.6 months; p = 0.04), it was not significantly associated with OS by IPWE after adjusting for adjuvant therapy [95%CI = (-)5.02-16.3; p = 0.3] or DFS on competing risk analysis (95%CI = 0.78-1.31; p = 0.96). Conclusions: Although NCRT is associated with improved pathologic surrogates, it is not associated with improved survival in PDA.
Variables | NC (N = 327) | NCRT (N = 91) | p-value (UVA) | p-value (MVA) |
---|---|---|---|---|
T size (cm) | 2.5 (2.0, 3.2) | 2.5 (1.6, 3) | 0.13 | 0.46 |
Lymph node ratio (LNR) | 0.05 (0.0, 0.14) | 0.03 (0.0, 0.12) | 0.04 | 0.14 |
LN positive | 230 (70.3) | 47 (51.6) | 0.001 | 0.007 |
Positive Margin (R1<1mm) | 173 (52.9) | 34 (37.4) | 0.008 | 0.22 |
Lymphovascular invasion (LVI) | 240 (76.7) | 49 (57.0) | < 0.001 | 0.02 |
Perineural invasion (PNI) | 274 (85.1) | 64 (70.3) | 0.002 | 0.21 |
Near-complete/ complete response | 12(3.8) | 11 (14.1) | < 0.001 | 0.13 |
DFS (months) | 15.1 (10.7, 24.5) | 17.0 (11.2, 31.5) | 0.056 | 0.96 |
OS (months) | 21.6 (14.3, 35.4) | 27.5 (14.9, 54.9) | 0.042 | 0.3 |
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