An international Multi-Institutional validation of T1 Sub-staging of intraductal papillary mucinous neoplasm-derived pancreatic cancer.

Intraductal Papillary Mucinous Neoplasm Invasive IPMN Pancreatic Cancer Pancreatic Cyst Pancreatic Neoplasms Staging

Journal

Journal of the National Cancer Institute
ISSN: 1460-2105
Titre abrégé: J Natl Cancer Inst
Pays: United States
ID NLM: 7503089

Informations de publication

Date de publication:
19 Jul 2024
Historique:
received: 02 05 2024
revised: 14 06 2024
accepted: 01 07 2024
medline: 20 7 2024
pubmed: 20 7 2024
entrez: 19 7 2024
Statut: aheadofprint

Résumé

Intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) is resected at smaller sizes compared to its biologically distinct counterpart, pancreatic intraepithelial neoplasia (PanIN)-derived PDAC. Thus, experts proposed T1 sub-staging for IPMN-derived PDAC. However, this has never been validated. Consecutive upfront surgery patients with IPMN-derived PDAC from five international high-volume centers were classified by the proposed T1 sub-staging classification (T1a ≤ 0.5, T1b > 0.5 and ≤1.0, and T1c >1.0 and ≤2.0 cm) using the invasive component size. Kaplan-Meier and log-rank tests were utilized to compare overall survival (OS). A multivariable Cox-regression was used to determine hazard ratios (HR) with confidence intervals (95%CI). Among 747 patients, 69 (9.2%), 50 (6.7%), 99 (13.0%), and 531 patients (71.1%), comprised the T1a, T1b, T1c, and T2-4 subgroups, respectively. Increasing T-stage was associated with elevated CA19-9, poorer grade, nodal positivity, R1-margin, and tubular subtype. Median OS for T1a, T1b, T1c, and T2-4 were 159.0 (95%CI:126.0-NR), 128.8 (98.3-NR), 77.6 (48.3-108.2), and 31.4 (27.5-37.7) months, respectively (p < .001). OS decreased with increasing T-stage for all pairwise comparisons (all p < .05). After risk-adjustment, age > 65, elevated CA19-9, T1b [HR : 2.55 (1.22-5.32)], T1c [HR : 3.04 (1.60-5.76)], and T2-4 [HR : 3.41 (1.89-6.17)] compared to T1a, nodal positivity, R1-margin, and no adjuvant chemotherapy were associated with worse OS. Disease recurrence was more common in T2-4 tumors (56.4%) compared to T1a (18.2%), T1b (23.9%), and T1c (36.1%, p < .001). T1 sub-staging of IPMN-derived PDAC is valid and has significant prognostic value. Advancing T1 sub-stage is associated with worse histopathology, survival, and recurrence. T1 sub-staging is recommended for future guidelines.

Sections du résumé

BACKGROUND BACKGROUND
Intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) is resected at smaller sizes compared to its biologically distinct counterpart, pancreatic intraepithelial neoplasia (PanIN)-derived PDAC. Thus, experts proposed T1 sub-staging for IPMN-derived PDAC. However, this has never been validated.
METHODS METHODS
Consecutive upfront surgery patients with IPMN-derived PDAC from five international high-volume centers were classified by the proposed T1 sub-staging classification (T1a ≤ 0.5, T1b > 0.5 and ≤1.0, and T1c >1.0 and ≤2.0 cm) using the invasive component size. Kaplan-Meier and log-rank tests were utilized to compare overall survival (OS). A multivariable Cox-regression was used to determine hazard ratios (HR) with confidence intervals (95%CI).
RESULTS RESULTS
Among 747 patients, 69 (9.2%), 50 (6.7%), 99 (13.0%), and 531 patients (71.1%), comprised the T1a, T1b, T1c, and T2-4 subgroups, respectively. Increasing T-stage was associated with elevated CA19-9, poorer grade, nodal positivity, R1-margin, and tubular subtype. Median OS for T1a, T1b, T1c, and T2-4 were 159.0 (95%CI:126.0-NR), 128.8 (98.3-NR), 77.6 (48.3-108.2), and 31.4 (27.5-37.7) months, respectively (p < .001). OS decreased with increasing T-stage for all pairwise comparisons (all p < .05). After risk-adjustment, age > 65, elevated CA19-9, T1b [HR : 2.55 (1.22-5.32)], T1c [HR : 3.04 (1.60-5.76)], and T2-4 [HR : 3.41 (1.89-6.17)] compared to T1a, nodal positivity, R1-margin, and no adjuvant chemotherapy were associated with worse OS. Disease recurrence was more common in T2-4 tumors (56.4%) compared to T1a (18.2%), T1b (23.9%), and T1c (36.1%, p < .001).
CONCLUSION CONCLUSIONS
T1 sub-staging of IPMN-derived PDAC is valid and has significant prognostic value. Advancing T1 sub-stage is associated with worse histopathology, survival, and recurrence. T1 sub-staging is recommended for future guidelines.

Identifiants

pubmed: 39029923
pii: 7717355
doi: 10.1093/jnci/djae166
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Auteurs

Joseph R Habib (JR)

Department of Surgery, New York University Langone Health, New York, USA.
Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands.
Regional Academic Cancer Center Utrecht, Utrecht, the Netherlands.

Ingmar F Rompen (IF)

Department of Surgery, New York University Langone Health, New York, USA.
Heidelberg University Hospital, Heidelberg, Germany.

Brady A Campbell (BA)

Department of Surgery, Johns Hopkins Hospital, Baltimore, USA.

Paul C M Andel (PCM)

Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands.
Regional Academic Cancer Center Utrecht, Utrecht, the Netherlands.

Benedict Kinny-Köster (B)

Heidelberg University Hospital, Heidelberg, Germany.

Ryte Damaseviciute (R)

Department of Surgery, New York University Langone Health, New York, USA.

D Brock Hewitt (D)

Department of Surgery, New York University Langone Health, New York, USA.

Greg D Sacks (GD)

Department of Surgery, New York University Langone Health, New York, USA.

Ammar A Javed (AA)

Department of Surgery, New York University Langone Health, New York, USA.

Marc G Besselink (MG)

Department of Surgery, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands.
Cancer Center Amsterdam, the Netherlands.

Hjalmar C van Santvoort (HC)

Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands.
Regional Academic Cancer Center Utrecht, Utrecht, the Netherlands.

Lois A Daamen (LA)

Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands.
Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, the Netherlands.

Martin Loos (M)

Heidelberg University Hospital, Heidelberg, Germany.

Jin He (J)

Department of Surgery, Johns Hopkins Hospital, Baltimore, USA.

I Quintus Molenaar (I)

Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands.
Regional Academic Cancer Center Utrecht, Utrecht, the Netherlands.

Markus W Büchler (MW)

Champalimaud Foundation, Lisbon, Portugal.

Christopher L Wolfgang (CL)

Department of Surgery, New York University Langone Health, New York, USA.

Classifications MeSH