Joseph R Habib, Ingmar F Rompen, Brady A Campbell, Paul C M Andel, Benedict Kinny-Köster, Ryte Damaseviciute, D Brock Hewitt, Greg D Sacks, Ammar A Javed, Marc G Besselink, Hjalmar C van Santvoort, Lois A Daamen, Martin Loos, Jin He, I Quintus Molenaar, Markus W Büchler, Christopher L Wolfgang
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However, this has never been validated.</p><p><strong>Methods: </strong>Consecutive upfront surgery patients with IPMN-derived PDAC from 5 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 used to compare overall survival (OS). A multivariable Cox regression was used to determine hazard ratios (HRs) with confidence intervals (95% CIs).</p><p><strong>Results: </strong>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 to NR), 128.8 (98.3 to NR), 77.6 (48.3 to 108.2), and 31.4 (27.5 to 37.7) months, respectively (P < .001). OS decreased with increasing T-stage for all pairwise comparisons (all P < .05). After risk adjustment, older than age 65, elevated CA19-9, T1b [HR = 2.55 (1.22 to 5.32)], T1c [HR = 3.04 (1.60 to 5.76)], and T2-4 [HR = 3.41 (1.89 to 6.17)] compared with 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 with T1a (18.2%), T1b (23.9%), and T1c (36.1%, P < .001).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":null,"pages":null},"PeriodicalIF":9.9000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542988/pdf/","citationCount":"0","resultStr":"{\"title\":\"An international multi-institutional validation of T1 sub-staging of intraductal papillary mucinous neoplasm-derived pancreatic cancer.\",\"authors\":\"Joseph R Habib, Ingmar F Rompen, Brady A Campbell, Paul C M Andel, Benedict Kinny-Köster, Ryte Damaseviciute, D Brock Hewitt, Greg D Sacks, Ammar A Javed, Marc G Besselink, Hjalmar C van Santvoort, Lois A Daamen, Martin Loos, Jin He, I Quintus Molenaar, Markus W Büchler, Christopher L Wolfgang\",\"doi\":\"10.1093/jnci/djae166\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) is resected at smaller sizes compared with 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.</p><p><strong>Methods: </strong>Consecutive upfront surgery patients with IPMN-derived PDAC from 5 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 used to compare overall survival (OS). A multivariable Cox regression was used to determine hazard ratios (HRs) with confidence intervals (95% CIs).</p><p><strong>Results: </strong>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 to NR), 128.8 (98.3 to NR), 77.6 (48.3 to 108.2), and 31.4 (27.5 to 37.7) months, respectively (P < .001). OS decreased with increasing T-stage for all pairwise comparisons (all P < .05). After risk adjustment, older than age 65, elevated CA19-9, T1b [HR = 2.55 (1.22 to 5.32)], T1c [HR = 3.04 (1.60 to 5.76)], and T2-4 [HR = 3.41 (1.89 to 6.17)] compared with 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 with T1a (18.2%), T1b (23.9%), and T1c (36.1%, P < .001).</p><p><strong>Conclusion: </strong>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. 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引用次数: 0
摘要
背景：导管内乳头状粘液瘤（IPMN）衍生的胰腺导管腺癌（PDAC）与其生物学上不同的对应物--胰腺上皮内瘤变（PanIN）衍生的PDAC相比，切除面积较小。因此，专家建议对 IPMN 衍生型 PDAC 进行 T1 亚分期。然而，这一观点从未得到验证：方法：根据提出的 T1 亚分期分类法（T1a ≤ 0.5、T1b > 0.5 且 ≤ 1.0、T1c > 1.0 且 ≤ 2.0 cm），使用侵袭性成分大小对来自五个国际高容量中心的连续 IPMN 衍生 PDAC 前期手术患者进行分类。采用卡普兰-梅耶（Kaplan-Meier）检验和对数秩检验比较总生存率（OS）。采用多变量考克斯回归法确定危险比（HR）及置信区间（95%CI）：在747名患者中，T1a、T1b、T1c和T2-4亚组分别有69人（9.2%）、50人（6.7%）、99人（13.0%）和531人（71.1%）。T分期的增加与CA19-9升高、分级较差、结节阳性、R1-边缘和管状亚型有关。T1a、T1b、T1c和T2-4的中位OS分别为159.0（95%CI:126.0-NR）、128.8（98.3-NR）、77.6（48.3-108.2）和31.4（27.5-37.7）个月（P 65，CA19-9升高，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.与T1a（18.2%）、T1b（23.9%）和T1c（36.1%）相比，疾病复发在T2-4肿瘤（56.4%）中更为常见：IPMN衍生型PDAC的T1亚分期是有效的，具有重要的预后价值。T1亚分期越前，组织病理学、生存率和复发率越差。建议将 T1 亚分期纳入未来指南。
An international multi-institutional validation of T1 sub-staging of intraductal papillary mucinous neoplasm-derived pancreatic cancer.
Background: Intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) is resected at smaller sizes compared with 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: Consecutive upfront surgery patients with IPMN-derived PDAC from 5 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 used to compare overall survival (OS). A multivariable Cox regression was used to determine hazard ratios (HRs) with confidence intervals (95% CIs).
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 to NR), 128.8 (98.3 to NR), 77.6 (48.3 to 108.2), and 31.4 (27.5 to 37.7) months, respectively (P < .001). OS decreased with increasing T-stage for all pairwise comparisons (all P < .05). After risk adjustment, older than age 65, elevated CA19-9, T1b [HR = 2.55 (1.22 to 5.32)], T1c [HR = 3.04 (1.60 to 5.76)], and T2-4 [HR = 3.41 (1.89 to 6.17)] compared with 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 with T1a (18.2%), T1b (23.9%), and T1c (36.1%, P < .001).
Conclusion: 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.
期刊介绍：
The Journal of the National Cancer Institute is a reputable publication that undergoes a peer-review process. It is available in both print (ISSN: 0027-8874) and online (ISSN: 1460-2105) formats, with 12 issues released annually. The journal's primary aim is to disseminate innovative and important discoveries in the field of cancer research, with specific emphasis on clinical, epidemiologic, behavioral, and health outcomes studies. Authors are encouraged to submit reviews, minireviews, and commentaries. The journal ensures that submitted manuscripts undergo a rigorous and expedited review to publish scientifically and medically significant findings in a timely manner.
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