High tumor budding is a strong predictor of poor prognosis in the resected perihilar cholangiocarcinoma patients regardless of neoadjuvant therapy, showing survival similar to those without resection

Itô, Takahiro; Kuriyama, Naohisa; Kikuchi, Yuji; Komatsubara, Haruna; Ichikawa, Kimihisa; Noguchi, Daisuke; Hayasaki, Aoi; Fujii, Tekehiro; Iizawa, Yusuke; Kato, Hiroyuki; Tanemura, Akihiro; Murata, Yasuhiro; Kishiwada, Masashi; Mizuno, Shugo; Usui, Masanobu; Sakurai, Hiroyuki; Isaji, Shuji

doi:10.1186/s12885-020-6695-9

Cited by 20 publications

(21 citation statements)

References 30 publications

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“…15 Unfortunately, the staging numbers did not correspond to the severity of the tumor. 16 Recently, unremitting efforts were taken to optimize prognostic models in PHC [17][18][19] ; however, the using linear approaches are challenging to model the complexity of tumour non-linear relationships with barely satisfactory discrimination. Genomic investigation of potential prognostic biomarker is rapidly developed, but still lacks certain clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Machine‐learning radiomics to predict early recurrence in perihilar cholangiocarcinoma after curative resection

Huan

Zhang

et al. 2020

Liver International

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Background and aims Up to 40%‐65% of patients with perihilar cholangiocarcinoma (PHC) rapidly progress to early recurrence (ER) even after curative resection. Quantification of ER risk is difficult and a reliable prognostic prediction tool is absent. We developed and validated a multilevel model, integrating clinicopathology, molecular pathology and radiology, especially radiomics coupled with machine‐learning algorithms, to predict the ER of patients after curative resection in PHC. Methods In total, 274 patients who underwent contrast‐enhanced CT (CECT) and curative resection at 2 institutions were retrospectively identified and randomly divided into training (n = 167), internal validation (n = 70) and external validation (n = 37) sets. A machine‐learning analysis of 18,120 radiomic features based on multiphase CECT and 48 clinico‐radiologic characteristics was performed for the multilevel model. Results Comprehensively, 7 independent factors (tumour differentiation, lymph node metastasis, pre‐operative CA19‐9 level, enhancement pattern, A‐Shrink score, V‐Shrink score and P‐Shrink score) were built to the multilevel model and quantified the risk of ER. We benchmarked the gain in discrimination with the area under the curve (AUC) of 0.883, superior to the rival clinical and radiomic models (AUCs 0.792‐0.805). The accuracy (ACC) of the multilevel model was 0.826, which was significantly higher than those of the conventional staging systems (AJCC 8th (0.641), MSKCC (0.617) and Gazzaniga (0.581)). Conclusion The radiomics‐based multilevel model demonstrated superior performance to rival models and conventional staging systems, and could serve as a visual prognostic tool to plan surveillance of ER and guide post‐operative individualized management in PHC.

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Section: Introductionmentioning

confidence: 99%

Machine‐learning radiomics to predict early recurrence in perihilar cholangiocarcinoma after curative resection

Huan

Zhang

et al. 2020

Liver International

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“…In our study, the frequency of regional lymph node metastasis was three‐fold greater in patients with high‐budding tumors than in patients with low‐ and intermediate‐budding tumors. Previous reports also suggest that tumor budding is associated with lymph node metastasis in patients with ICC or perihilar cholangiocarcinoma 21,24 . Namely, patients with metastatic lymph nodes who did not undergo lymphadenectomy might be identified as T4N0, which is the same as patients with stage IVA showing T1‐3N1 disease.…”

Section: Discussionmentioning

confidence: 92%

“…Previous reports also suggest that tumor budding is associated with lymph node metastasis in patients with ICC or perihilar cholangiocarcinoma. 21 , 24 Namely, patients with metastatic lymph nodes who did not undergo lymphadenectomy might be identified as T4N0, which is the same as patients with stage IVA showing T1‐3N1 disease.…”

Section: Discussionmentioning

confidence: 99%

Tumor budding may be a promising prognostic indicator in intrahepatic cholangiocarcinoma: A multicenter retrospective study

Kosaka

Ishida

Ueno

et al. 2022

Annals of Gastroent Surgery

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Purpose This retrospective study evaluated our hypothesis that high tumor budding (≥10 buds) may help determine the appropriate T category for more accurate staging of intrahepatic cholangiocarcinoma (ICC). Methods We analyzed the clinical and histopathologic data of 235 consecutive patients with histologically confirmed ICC following hepatectomy at five university hospitals in the Kansai region of Japan between January 2009 and December 2020. ICC staging was based on the Liver Cancer Study Group of Japan (LCSGJ) staging system, 6th edition. Results Patients with ICC with high budding showed significantly shorter disease‐specific survival (DSS) and disease‐free survival (DFS) than patients with low/intermediate budding. Cox proportional hazards regression analysis showed a hazard ratio of 2.2‐2.3 (P < 0.05) for high budding. Based on these results, we modified the T category of ICC in the LCSGJ staging system by adding severity of tumor budding as a fourth determinant. This proposed staging system for ICC has significantly improved the prognostic accuracy for both DSS and DFS (both: P < 0.05). Conclusions High tumor budding is a new candidate for an additional determinant of the T category in staging ICC. An LCSGJ staging system containing an additional evaluation of tumor budding may lead to improved staging accuracy.

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“…In these patients, indication of curative-intent surgery should be carefully performed by prolonging preoperative therapy as a watch and wait approach. Additionally, our recent study demonstrated that high tumor budding (TB) can be a novel poor prognostic factor in resected perihilar cholangiocarcinoma regardless of neoadjuvant therapy [33] as well as various type of cancers such as esophageal [34] and pancreas [35]. However, the TB cannot be evaluated before surgery.…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant chemotherapy followed by curative-intent surgery for perihilar cholangiocarcinoma based on its anatomical resectability classification and lymph node status

et al. 2020

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Background: The prognosis of patients with perihilar cholangiocarcinoma have been unsatisfactory. We established new anatomical resectability classification for patients with localized perihilar cholangiocarcinoma and performed neoadjuvant chemotherapy followed by curative-intent surgery based on its resectability classification and lymph node status to improve prognosis. This study aimed to clarify the long-term outcomes and validation of our strategy. Methods: Between September 2010 and August 2018, 72 consecutive patients with perihilar cholangiocarcinoma were classified into three groups: Resectable (R = 29), Borderline resectable (BR = 23), and Locally advanced (LA = 20), based on the two factors of tumor vascular and biliary extension. R with clinically lymph node metastasis, BR, and LA patients received neoadjuvant chemotherapy using gemcitabine plus S-1. Results: Forty-seven patients (65.3%) received neoadjuvant chemotherapy: R in 8, BR in 21, and 18 in LA, respectively. Fifty-nine patients (68.1%) underwent curative-intent surgery: R in 26, BR in 17, and LA in 6. Five-year disease-specific survival was 31.5% (median survival time: 33.0 months): 50.3% (not reached) in R, 30.0% (31.4 months) in BR, and 16.5% (22.5 months) in LA, which were relatively stratified. Among 49 patients with resection, disease-specific survival was 43.8% (57.0 months): 57.6% (not reached) in R, 41.0% (52.4 months) in BR, and 0% (49.4 months) in LA, which were significantly good prognosis compared to 23 patients without resection (17.2 months). Multivariate analysis identified preoperative high carcinoembryonic antigen levels (more than 8.5 ng/ml) and pT4 as independent poor prognostic factor of patients with resection. Conclusion: Neoadjuvant chemotherapy based on resectability classification and lymph node status was feasible, and was considered efficacious in selected patients.

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High tumor budding is a strong predictor of poor prognosis in the resected perihilar cholangiocarcinoma patients regardless of neoadjuvant therapy, showing survival similar to those without resection

Cited by 20 publications

References 30 publications

Machine‐learning radiomics to predict early recurrence in perihilar cholangiocarcinoma after curative resection

Machine‐learning radiomics to predict early recurrence in perihilar cholangiocarcinoma after curative resection

Tumor budding may be a promising prognostic indicator in intrahepatic cholangiocarcinoma: A multicenter retrospective study

Neoadjuvant chemotherapy followed by curative-intent surgery for perihilar cholangiocarcinoma based on its anatomical resectability classification and lymph node status

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