Post-neoadjuvant cellular dissociation grading based on tumour budding and cell nest size is associated with therapy response and survival in oesophageal squamous cell carcinoma

Abstract

Background Cellular Dissociation Grade (CDG) composed of tumour budding and cell nest size has been shown to independently predict prognosis in pre-therapeutic biopsies and primary resections of oesophageal squamous cell carcinoma (ESCC). Here, we aimed to evaluate the prognostic impact of CDG in ESCC after neoadjuvant therapy. Methods We evaluated cell nest size and tumour budding activity in 122 post-neoadjuvant ESCC resections, correlated the results with tumour regression groups and patient survival and compared the results with data from primary resected cases as well as pre-therapeutic biopsies. Results CDG remained stable when results from pre-therapeutic biopsies and post-therapeutic resections from the same patient were compared. CDG was associated with therapy response and a strong predictor of overall, disease-specific (DSS) and disease-free (DFS) survival in univariate analysis and—besides metastasis—remained the only significant survival predictor for DSS and DFS in multivariate analysis. Multivariate DFS hazard ratios reached 3.3 for CDG-G2 and 4.9 for CDG-G3 neoplasms compared with CDG-G1 carcinomas (p = 0.016). Conclusions CDG is the only morphology-based grading algorithm published to date, which in concert with regression grading, is able to contribute relevant prognostic information in the post-neoadjuvant setting of ESCC.

Tumour budding and CD8+ T cells: ‘attackers’ and ‘defenders’ in rectal cancer with and without neoadjuvant chemoradiotherapy

“…In patients who have undergone neoadjuvant treatment, peritumoural budding has previously been called ‘false budding’, and has been assessed according to their cellular dissociation grade, on the presumption that this is a treatment effect rather than an intrinsic feature of tumour biology. The role of tumour budding in the context is largely unknown, although some studies suggest that its presence is associated with poor response and short survival in both rectal and oesophageal cancers 13–15 . Some studies suggest that a high degree of tumour budding or cellular dissociation is associated with worse tumour responsiveness in neoadjuvantly treated rectal and oesophageal cancers and significantly more unfavourable survival time.…”

Updates in staging and pathologic evaluation of esophageal carcinoma following neoadjuvant therapy

“…A score of 2–3 is CDG‐G1 (well differentiated), 4–5 is CDG‐G2 (moderately differentiated), and 6–7 is CDG‐G3 (poorly differentiated) 44,45 . This grading scheme demonstrated a strong ability to predict patient outcomes and also correlated well with the conventional TRG systems in patients with ESCCs 44 . This CDG scheme needs to be evaluated in postneoadjuvant EACs as well, since high‐grade tumor budding and/or poorly differentiated tumor cell clusters are closely associated with poor outcomes in EAC 46,47 …”

“…The sum of both parameters gives the final CDG score ranging from 2 to 7. A score of 2–3 is CDG‐G1 (well differentiated), 4–5 is CDG‐G2 (moderately differentiated), and 6–7 is CDG‐G3 (poorly differentiated) 44,45 . This grading scheme demonstrated a strong ability to predict patient outcomes and also correlated well with the conventional TRG systems in patients with ESCCs 44 .…”

“…4). 44 Specifically, CDG is a combined scoring scheme incorporating both tumor budding and cell nest size. Residual tumors are given a score of 1 without tumor budding, a score of 2 with low tumor budding (<5 buds/HPF), and a score of 3 with high tumor budding (≥5 buds/HPF).…”

Combined assessment of tumour cell nest size and desmoplastic reaction as an excellent prognostic predictor in oesophageal squamous cell carcinoma

“…15 DR is linked to tumour-associated fibroblasts and their secreted matrix, involved in promoting tumour cells proliferation and enhancing the invasiveness of tumour cells. [27][28][29] Thereafter, an emerging 3-tiered grading system based on TB activity and CNS termed Cellular Dissociation Grading has been widely investigated in squamous cell carcinomas of various sites including lung, oral cavity, larynx, hypopharynx, and oesophagus, [11][12][13][14][15][30][31] and proved to be a strong predictor of patient outcomes. However, there are several drawbacks of the Cellular Dissociation Grading system.…”