Validation of the International Tumor Budding Consensus Conference 2016 recommendations on tumor budding in stage I-IV colorectal cancer

Abstract Background Tumor budding is an independent prognostic factor in colorectal cancer (CRC) and has recently been well-defined by the International Tumour Budding Consensus Conference (ITBCC). Objective The aim of the present study was to use the ITBCC budding evaluation method to examine the relationship between tumor budding, tumor factors, tumor microenvironment, and survival in patients with primary operable CRC. Methods Hematoxylin and eosin-stained slides of 952 CRC patients diagnosed between 1997 and 2007 were evaluated for tumor budding according to the ITBCC criteria. The tumor microenvironment was evaluated using tumor stroma percentage (TSP) and Klintrup–Makinen (KM) grade to assess the tumor inflammatory cell infiltrate. Results High budding (n = 268, 28%) was significantly associated with TNM stage (p < 0.001), competent mismatch repair (MMR; p < 0.05), venous invasion (p < 0.001), weak KM grade (p < 0.001), high TSP (p < 0.001), and reduced cancer-specific survival (CSS) (hazard ratio 8.68, 95% confidence interval 6.30–11.97; p < 0.001). Tumor budding effectively stratifies CSS stage T1 through to T4 (all p < 0.05) independent of associated factors. Conclusions Tumor budding effectively stratifies patients’ survival in primary operable CRC independent of other phenotypic features. In particular, the combination of T stage and budding should form the basis of a new staging system for primary operable CRC.

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Tumor budding is a strong predictor of disease-free survival in stage II colorectal cancer: Validation study based on the International Tumor Budding Consensus Conference (ITBCC) recommendations.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.594 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 594-594 ◽

Cited By ~ 6

Author(s):

Heather Dawson ◽

Naziheh Assarzadegan ◽

Robert Riddell ◽

Richard Kirsch ◽

Annika Blank ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Cells ◽

Disease Free Survival ◽

The United States ◽

Consensus Conference ◽

Stage Ii ◽

Tumor Budding ◽

Free Survival ◽

Staging Systems ◽

Disease Free

594 Background: Tumor budding, defined as single tumor cells or small clusters of four or less tumor cells at the invasive front, has been shown to be a strong and independent prognostic factor in colorectal cancer (CRC). However, widespread reporting of tumor budding has been held back largely due to a lack of consensus on scoring methods. 23 experts from the United States, Canada, Japan and Europe participated at the International Tumor Budding Consensus Conference (ITBCC), held in April 2016 in Bern, Switzerland, and agreed on a set of recommendations for assessing and reporting tumor budding in CRC. The aim of this study was to validate the method proposed by ITBCC in the clinically relevant scenario of Stage II CRC. Methods: In 151 Stage II CRC patients, tumor budding was assessed on scanned H&E-stained slides in a single hot spot measuring 0.785mm2. Cutoffs as defined by ITBCC were used: Low (Bd1): 0-4 buds, intermediate (Bd2): 5-9 buds, high (Bd3): ≥ 10 buds. Statistical analysis for associations with clinicopathological features, disease free survival (DFS) and overall survival (OS) was performed. Results: The average number of buds/hotspot was 6.8 (median 5.0). 43.1% of cases were Bd1, 27.2% Bd2 and 29.8% Bd3. Tumor budding as a continuous variable was associated with extramural venous invasion (EMVI) (p = 0.05). Tumor budding was associated with poorer OS in univariate analysis (p = 0.0386, HR 1.048, 95%CI 1.002-1.095). For 3- and 5- year DFS, Bd3 was associated with significantly worse survival in comparison with Bd1/2 (p = 0.0031 and p = 0.0025, respectively). In multivariate analysis adjusting for pT, tumor grade and EMVI, tumor budding retained its adverse prognostic effect for DFS (p = 0.006, HR 3.293, 95%CI 1.66-6.53). Conclusions: This study provides promising data on tumor budding assessed by the ITBCC method in the Stage II scenario. Especially Bd3 shows a detrimental adverse impact on DFS in comparison to Bd1/Bd2. Based on the ITBCC, tumor budding has the potential to strongly affect the management of Stage II CRC patients and should be therefore included in reporting guidelines and staging systems in CRC.

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Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016

Modern Pathology ◽

10.1038/modpathol.2017.46 ◽

2017 ◽

Vol 30 (9) ◽

pp. 1299-1311 ◽

Cited By ~ 232

Author(s):

Alessandro Lugli ◽

Richard Kirsch ◽

Yoichi Ajioka ◽

Fred Bosman ◽

Gieri Cathomas ◽

...

Keyword(s):

Colorectal Cancer ◽

Consensus Conference ◽

Tumor Budding

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Refining the ITBCC tumor budding scoring system with a “zero-budding” category in colorectal cancer

Virchows Archiv ◽

10.1007/s00428-021-03090-w ◽

2021 ◽

Author(s):

Inti Zlobec ◽

Melanie Bächli ◽

Francesca Galuppini ◽

Martin D. Berger ◽

Heather E. Dawson ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Factors ◽

Clinical Relevance ◽

Perineural Invasion ◽

Tumor Grade ◽

Consensus Conference ◽

Clinicopathological Features ◽

Tumor Budding ◽

Additional Information ◽

Significant Difference

AbstractTumor budding scoring guidelines from the International Tumor Budding Consensus Conference (ITBCC) for colorectal cancer propose three groups: BD1 (0–4 buds/0.785 mm2), BD2 (5–9 buds/0.785 mm2), and BD3 (10 or more buds/0.785 mm2). Here, we investigate whether a fourth scoring category, namely zero buds, may have additional clinical relevance. The number of tumor buds/0.785 mm2 was scored in 959 cases. Those with zero tumor buds were considered BD0, while a new BD1 category of 1–4 buds was proposed. Associations of both scoring approaches with clinicopathological features were analyzed. Conventional ITBCC scoring showed expected associations with unfavorable histopathological prognostic factors. In total, 111/959 (11.6%) were BD0. A significant difference was found when BD0 was compared statistically to BD1 (1–4 buds) for pT, TNM, tumor grade, and lymphatic, venous, and perineural invasion (p < 0.01, all). Tumors with BD0 occur relatively frequently and contribute additional information on tumor behavior. BD0 should be considered for subsequent ITBCC guidelines.

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Improving tumor budding reporting in colorectal cancer: a Delphi consensus study

Virchows Archiv ◽

10.1007/s00428-021-03059-9 ◽

2021 ◽

Author(s):

Tariq Sami Haddad ◽

Alessandro Lugli ◽

Susan Aherne ◽

Valeria Barresi ◽

Benoît Terris ◽

...

Keyword(s):

Colorectal Cancer ◽

Health Care Professionals ◽

Consensus Conference ◽

Tumor Budding ◽

Delphi Consensus ◽

International Evidence ◽

Modified Delphi ◽

Cancer Pathology ◽

Gastrointestinal Pathology ◽

Continued Use

AbstractTumor budding is a long-established independent adverse prognostic marker in colorectal cancer, yet methods for its assessment have varied widely. In an effort to standardize its reporting, a group of experts met in Bern, Switzerland, in 2016 to reach consensus on a single, international, evidence-based method for tumor budding assessment and reporting (International Tumor Budding Consensus Conference [ITBCC]). Tumor budding assessment using the ITBCC criteria has been validated in large cohorts of cancer patients and incorporated into several international colorectal cancer pathology and clinical guidelines. With the wider reporting of tumor budding, new issues have emerged that require further clarification. To better inform researchers and health-care professionals on these issues, an international group of experts in gastrointestinal pathology participated in a modified Delphi process to generate consensus and highlight areas requiring further research. This effort serves to re-affirm the importance of tumor budding in colorectal cancer and support its continued use in routine clinical practice.

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