title: Construction of a pathological risk model of occult lymph node metastases for prognostication by semi-automated image analysis of tumor budding in early-stage oral squamous cell carcinoma.
abstract: It is challenging to identify at diagnosis those patients with early oral squamous cell carcinoma (OSCC), who have a poor prognosis and those that have a high risk of harboring occult lymph node metastases. The aim of this study was to develop a standardized and objective digital scoring method to evaluate the predictive value of tumor budding. We developed a semi-automated image-analysis algorithm, Digital Tumor Bud Count (DTBC), to evaluate tumor budding. The algorithm was tested in 222 consecutive patients with early-stage OSCC and major endpoints were overall (OS) and progression free survival (PFS). We subsequently constructed and cross-validated a binary logistic regression model and evaluated its clinical utility by decision curve analysis. A high DTBC was an independent predictor of both poor OS and PFS in a multivariate Cox regression model. The logistic regression model was able to identify patients with occult lymph node metastases with an area under the curve (AUC) of 0.83 (95% CI: 0.78-0.89, P <0.001) and a 10-fold cross-validated AUC of 0.79. Compared to other known histopathological risk factors, the DTBC had a higher diagnostic accuracy. The proposed, novel risk model could be used as a guide to identify patients who would benefit from an up-front neck dissection.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Nicklas Juel
authors.initials: NJ
authors.lastname: Pedersen
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: David Hebbelstrup
authors.initials: DH
authors.lastname: Jensen
authors.affiliation: Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Giedrius
authors.initials: G
authors.lastname: Lelkaitis
authors.affiliation: Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Katalin
authors.initials: K
authors.lastname: Kiss
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Charabi
authors.affiliation: Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Lena
authors.initials: L
authors.lastname: Specht
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: von Buchwald
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000473:pathology; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000000981:diagnostic imaging* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis
keywords: REMARK guidelines; digital pathology; oral squamous cell carcinoma; tumor budding