Prognosis Associated With CA19-9 Response Dynamics and Normalization During Neoadjuvant Therapy in Resected Pancreatic Adenocarcinoma

Timothy E. Newhook; Timothy J. Vreeland; James F. Griffin; Rebecca S.S. Tidwell; Laura R. Prakash; Eugene J. Koay; Ethan B. Ludmir; Brandon G. Smaglo; Shubham Pant; Michael Overman; Robert A. Wolff; Naruhiko Ikoma; Jessica Maxwell; Michael P. Kim; Jeffrey E. Lee; Matthew H.G. Katz; Ching Wei D. Tzeng

doi:10.1097/SLA.0000000000005184

Prognosis Associated With CA19-9 Response Dynamics and Normalization During Neoadjuvant Therapy in Resected Pancreatic Adenocarcinoma

Timothy E. Newhook, Timothy J. Vreeland, James F. Griffin, Rebecca S.S. Tidwell, Laura R. Prakash, Eugene J. Koay, Ethan B. Ludmir, Brandon G. Smaglo, Shubham Pant, Michael Overman, Robert A. Wolff, Naruhiko Ikoma, Jessica Maxwell, Michael P. Kim, Jeffrey E. Lee, Matthew H.G. Katz, Ching Wei D. Tzeng

Houston Methodist

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

Abstract

OBJECTIVE: To characterize associations between carbohydrate antigen 19-9 (CA19-9) dynamics during neoadjuvant therapy (NT) and survival for patients with pancreatic ductal adenocarcinoma (PDAC).

BACKGROUND: Although normalization of CA19-9 during NT is associated with improved outcomes following PDAC resection, we hypothesize that CA19-9 dynamics during NT can improve prognostication.

METHODS: Characteristics for patients with PDAC undergoing NT (July 2011-October 2018) with ≥3 CA19-9 results (bilirubin<2mg/dL) were collected and grouped by CA19-9 dynamics. Nonproducers (<1 U/ml) were excluded, and normal was ≤35 U/ml. Postresection survival was compared among groups.

RESULTS: Of 431 patients, 166 had eligible CA19-9 values. Median baseline CA19-9 was 98 U/ml. Overall 2-year postresection recurrence-free survival (RFS) and overall survival (OS) were 37% and 63%, respectively. Patients with normalization (53%) had improved 2-year RFS (47% vs. 28%, P = 0.01) and OS (75% vs. 49%, P = 0.01). CA19-9 dynamics during NT were analyzed by shape, direction, and normalization creating response types ("A-B-C-D-E"). Type A was "Always" decreasing to normalization, B "Bidirectional" with eventual normalization, C "Consistently" normal, D any "Decrease" without normalization, and E "Elevating" without normalization. Types A and B responses were associated with the longest postresection 2-year RFS (51% and 56%) and OS (75% and 92%, respectively) whereas Types D and E had the worst outcomes. After adjusting for node-positivity, perineural invasion, and margin-positivity, CA19-9 response types were independently associated with both RFS and OS, and predicted outcomes are better than CA19-9 normalization alone (likelihood ratio test RFS P < 0.001, OS P = 0.01).

CONCLUSIONS: This novel A-B-C-D-E classification of CA19-9 dynamics during NT was associated with postresection outcomes more precisely than CA19-9 normalization alone.

Original language	English (US)
Pages (from-to)	484-490
Number of pages	7
Journal	Annals of surgery
Volume	277
Issue number	3
DOIs	https://doi.org/10.1097/SLA.0000000000005184
State	Published - Mar 1 2023

Keywords

CA19-9
carbohydrate antigen 19-9
neoadjuvant therapy
pancreatic adenocarcinoma
Pancreatic Neoplasms/surgery
Prognosis
Adenocarcinoma/surgery
Humans
Carcinoma, Pancreatic Ductal/surgery
Neoadjuvant Therapy
Retrospective Studies
CA-19-9 Antigen

ASJC Scopus subject areas

Surgery

Access to Document

10.1097/SLA.0000000000005184

Cite this

Newhook, T. E., Vreeland, T. J., Griffin, J. F., Tidwell, R. S. S., Prakash, L. R., Koay, E. J., Ludmir, E. B., Smaglo, B. G., Pant, S., Overman, M., Wolff, R. A., Ikoma, N., Maxwell, J., Kim, M. P., Lee, J. E., Katz, M. H. G., & Tzeng, C. W. D. (2023). Prognosis Associated With CA19-9 Response Dynamics and Normalization During Neoadjuvant Therapy in Resected Pancreatic Adenocarcinoma. Annals of surgery, 277(3), 484-490. https://doi.org/10.1097/SLA.0000000000005184

Newhook, TE, Vreeland, TJ, Griffin, JF, Tidwell, RSS, Prakash, LR, Koay, EJ, Ludmir, EB, Smaglo, BG, Pant, S, Overman, M, Wolff, RA, Ikoma, N, Maxwell, J, Kim, MP, Lee, JE, Katz, MHG & Tzeng, CWD 2023, 'Prognosis Associated With CA19-9 Response Dynamics and Normalization During Neoadjuvant Therapy in Resected Pancreatic Adenocarcinoma', Annals of surgery, vol. 277, no. 3, pp. 484-490. https://doi.org/10.1097/SLA.0000000000005184

@article{05505edda5de490daf0d9ffd7e9ee2e1,

title = "Prognosis Associated With CA19-9 Response Dynamics and Normalization During Neoadjuvant Therapy in Resected Pancreatic Adenocarcinoma",

abstract = "OBJECTIVE: To characterize associations between carbohydrate antigen 19-9 (CA19-9) dynamics during neoadjuvant therapy (NT) and survival for patients with pancreatic ductal adenocarcinoma (PDAC).BACKGROUND: Although normalization of CA19-9 during NT is associated with improved outcomes following PDAC resection, we hypothesize that CA19-9 dynamics during NT can improve prognostication.METHODS: Characteristics for patients with PDAC undergoing NT (July 2011-October 2018) with ≥3 CA19-9 results (bilirubin<2mg/dL) were collected and grouped by CA19-9 dynamics. Nonproducers (<1 U/ml) were excluded, and normal was ≤35 U/ml. Postresection survival was compared among groups.RESULTS: Of 431 patients, 166 had eligible CA19-9 values. Median baseline CA19-9 was 98 U/ml. Overall 2-year postresection recurrence-free survival (RFS) and overall survival (OS) were 37% and 63%, respectively. Patients with normalization (53%) had improved 2-year RFS (47% vs. 28%, P = 0.01) and OS (75% vs. 49%, P = 0.01). CA19-9 dynamics during NT were analyzed by shape, direction, and normalization creating response types ({"}A-B-C-D-E{"}). Type A was {"}Always{"} decreasing to normalization, B {"}Bidirectional{"} with eventual normalization, C {"}Consistently{"} normal, D any {"}Decrease{"} without normalization, and E {"}Elevating{"} without normalization. Types A and B responses were associated with the longest postresection 2-year RFS (51% and 56%) and OS (75% and 92%, respectively) whereas Types D and E had the worst outcomes. After adjusting for node-positivity, perineural invasion, and margin-positivity, CA19-9 response types were independently associated with both RFS and OS, and predicted outcomes are better than CA19-9 normalization alone (likelihood ratio test RFS P < 0.001, OS P = 0.01).CONCLUSIONS: This novel A-B-C-D-E classification of CA19-9 dynamics during NT was associated with postresection outcomes more precisely than CA19-9 normalization alone.",

keywords = "CA19-9, carbohydrate antigen 19-9, neoadjuvant therapy, pancreatic adenocarcinoma, Pancreatic Neoplasms/surgery, Prognosis, Adenocarcinoma/surgery, Humans, Carcinoma, Pancreatic Ductal/surgery, Neoadjuvant Therapy, Retrospective Studies, CA-19-9 Antigen",

author = "Newhook, {Timothy E.} and Vreeland, {Timothy J.} and Griffin, {James F.} and Tidwell, {Rebecca S.S.} and Prakash, {Laura R.} and Koay, {Eugene J.} and Ludmir, {Ethan B.} and Smaglo, {Brandon G.} and Shubham Pant and Michael Overman and Wolff, {Robert A.} and Naruhiko Ikoma and Jessica Maxwell and Kim, {Michael P.} and Lee, {Jeffrey E.} and Katz, {Matthew H.G.} and Tzeng, {Ching Wei D.}",

year = "2023",

month = mar,

day = "1",

doi = "10.1097/SLA.0000000000005184",

language = "English (US)",

volume = "277",

pages = "484--490",

journal = "Annals of surgery",

issn = "0003-4932",

publisher = "Wolters Kluwer Health",

number = "3",

}

TY - JOUR

T1 - Prognosis Associated With CA19-9 Response Dynamics and Normalization During Neoadjuvant Therapy in Resected Pancreatic Adenocarcinoma

AU - Newhook, Timothy E.

AU - Vreeland, Timothy J.

AU - Griffin, James F.

AU - Tidwell, Rebecca S.S.

AU - Prakash, Laura R.

AU - Koay, Eugene J.

AU - Ludmir, Ethan B.

AU - Smaglo, Brandon G.

AU - Pant, Shubham

AU - Overman, Michael

AU - Wolff, Robert A.

AU - Ikoma, Naruhiko

AU - Maxwell, Jessica

AU - Kim, Michael P.

AU - Lee, Jeffrey E.

AU - Katz, Matthew H.G.

AU - Tzeng, Ching Wei D.

PY - 2023/3/1

Y1 - 2023/3/1

N2 - OBJECTIVE: To characterize associations between carbohydrate antigen 19-9 (CA19-9) dynamics during neoadjuvant therapy (NT) and survival for patients with pancreatic ductal adenocarcinoma (PDAC).BACKGROUND: Although normalization of CA19-9 during NT is associated with improved outcomes following PDAC resection, we hypothesize that CA19-9 dynamics during NT can improve prognostication.METHODS: Characteristics for patients with PDAC undergoing NT (July 2011-October 2018) with ≥3 CA19-9 results (bilirubin<2mg/dL) were collected and grouped by CA19-9 dynamics. Nonproducers (<1 U/ml) were excluded, and normal was ≤35 U/ml. Postresection survival was compared among groups.RESULTS: Of 431 patients, 166 had eligible CA19-9 values. Median baseline CA19-9 was 98 U/ml. Overall 2-year postresection recurrence-free survival (RFS) and overall survival (OS) were 37% and 63%, respectively. Patients with normalization (53%) had improved 2-year RFS (47% vs. 28%, P = 0.01) and OS (75% vs. 49%, P = 0.01). CA19-9 dynamics during NT were analyzed by shape, direction, and normalization creating response types ("A-B-C-D-E"). Type A was "Always" decreasing to normalization, B "Bidirectional" with eventual normalization, C "Consistently" normal, D any "Decrease" without normalization, and E "Elevating" without normalization. Types A and B responses were associated with the longest postresection 2-year RFS (51% and 56%) and OS (75% and 92%, respectively) whereas Types D and E had the worst outcomes. After adjusting for node-positivity, perineural invasion, and margin-positivity, CA19-9 response types were independently associated with both RFS and OS, and predicted outcomes are better than CA19-9 normalization alone (likelihood ratio test RFS P < 0.001, OS P = 0.01).CONCLUSIONS: This novel A-B-C-D-E classification of CA19-9 dynamics during NT was associated with postresection outcomes more precisely than CA19-9 normalization alone.

AB - OBJECTIVE: To characterize associations between carbohydrate antigen 19-9 (CA19-9) dynamics during neoadjuvant therapy (NT) and survival for patients with pancreatic ductal adenocarcinoma (PDAC).BACKGROUND: Although normalization of CA19-9 during NT is associated with improved outcomes following PDAC resection, we hypothesize that CA19-9 dynamics during NT can improve prognostication.METHODS: Characteristics for patients with PDAC undergoing NT (July 2011-October 2018) with ≥3 CA19-9 results (bilirubin<2mg/dL) were collected and grouped by CA19-9 dynamics. Nonproducers (<1 U/ml) were excluded, and normal was ≤35 U/ml. Postresection survival was compared among groups.RESULTS: Of 431 patients, 166 had eligible CA19-9 values. Median baseline CA19-9 was 98 U/ml. Overall 2-year postresection recurrence-free survival (RFS) and overall survival (OS) were 37% and 63%, respectively. Patients with normalization (53%) had improved 2-year RFS (47% vs. 28%, P = 0.01) and OS (75% vs. 49%, P = 0.01). CA19-9 dynamics during NT were analyzed by shape, direction, and normalization creating response types ("A-B-C-D-E"). Type A was "Always" decreasing to normalization, B "Bidirectional" with eventual normalization, C "Consistently" normal, D any "Decrease" without normalization, and E "Elevating" without normalization. Types A and B responses were associated with the longest postresection 2-year RFS (51% and 56%) and OS (75% and 92%, respectively) whereas Types D and E had the worst outcomes. After adjusting for node-positivity, perineural invasion, and margin-positivity, CA19-9 response types were independently associated with both RFS and OS, and predicted outcomes are better than CA19-9 normalization alone (likelihood ratio test RFS P < 0.001, OS P = 0.01).CONCLUSIONS: This novel A-B-C-D-E classification of CA19-9 dynamics during NT was associated with postresection outcomes more precisely than CA19-9 normalization alone.

KW - CA19-9

KW - carbohydrate antigen 19-9

KW - neoadjuvant therapy

KW - pancreatic adenocarcinoma

KW - Pancreatic Neoplasms/surgery

KW - Prognosis

KW - Adenocarcinoma/surgery

KW - Humans

KW - Carcinoma, Pancreatic Ductal/surgery

KW - Neoadjuvant Therapy

KW - Retrospective Studies

KW - CA-19-9 Antigen

UR - http://www.scopus.com/inward/record.url?scp=85132552241&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85132552241&partnerID=8YFLogxK

U2 - 10.1097/SLA.0000000000005184

DO - 10.1097/SLA.0000000000005184

M3 - Article

C2 - 36649067

AN - SCOPUS:85132552241

SN - 0003-4932

VL - 277

SP - 484

EP - 490

JO - Annals of surgery

JF - Annals of surgery

IS - 3

ER -

Prognosis Associated With CA19-9 Response Dynamics and Normalization During Neoadjuvant Therapy in Resected Pancreatic Adenocarcinoma

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this