Christian Mirian1, Thomas A Gerds2, Maria M Pedersen3, Mischa de Ridder4, Alfons Balm4, Davide Mattavelli5, Cesare Piazza5, Lasse R Jensen6, Deepak Balasubramanian7, Narayana Subramaniam7, Yogesh Dokhe7, Krishnakumar Thankappan7, Subramania Iyer7, Sana D Karam8, Susanne Wiegand9, Linda Feeley10, Chris Milross11, Kan Gao12, Carsten E Palme13, Tsu-Hui Hubert Low13, Ruta Gupta14, Christian Freudlsperger15, Julius Moratin15, Patrick Sheahan16, Jonathan Clark13, Therese Ovesen17. 1. Department of Otorhinolaryngology, Region Hospital West Jutland, Holstebro, Denmark. Electronic address: Christian.mirian.larsen@regionh.dk. 2. Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark. 3. Department of Oncology, Aarhus University Hospital, Aarhus, Denmark. 4. Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands; Department of Oral and Maxillofacial Surgery, Amsterdam University Medical Center, Amsterdam, the Netherlands. 5. Unit of Otorhinolaryngology - Head and Neck Surgery, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy. 6. Department of Otorhinolaryngology, Region Hospital West Jutland, Holstebro, Denmark. 7. Department of Head and Neck Surgery, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, India. 8. Department of Radiation Oncology, Anschutz Medical Campus, University of Colorado, Aurora, CO, USA. 9. Department of Otolaryngology, Head and Neck Surgery, University Hospital Leipzig, Leipzig, Germany. 10. Department of Pathology, Cork University Hospital, Cork, Ireland; ENTO Research Unit, College of Medicine and Health, University College Cork, Cork, Ireland. 11. Sydney Medical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, Australia; Department of Radiation Oncology, Chris O'Brien Lifehouse, Sydney, Australia. 12. Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, Australia. 13. Sydney Medical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, Australia; Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, Australia; Royal Prince Alfred Institute of Academic Surgery, Sydney Local Health District, Sydney, Australia. 14. Sydney Medical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, Australia; Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, Australia; Department of Tissue Pathology and Diagnostic Oncology, NSW Health Pathology, Sydney, Australia. 15. Department of Oral and Cranio-Maxillofacial Surgery, Heidelberg University Hospital, Heidelberg, Germany. 16. ENTO Research Unit, College of Medicine and Health, University College Cork, Cork, Ireland; Department of Otolaryngology - Head and Neck Surgery, South Infirmary Victoria, University Hospital, Cork, Ireland; Department of Surgery, University College Cork, Cork, Ireland. 17. Department of Otorhinolaryngology, Region Hospital West Jutland, Holstebro, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus C, Denmark.
Abstract
BACKGROUND: We aimed to compare the predictive performance of pN-categories in oral squamous cell carcinoma (OSCC) encompassing the most recent 8th edition (TNM8), its predecessor (TNM7), and a newly proposed algorithm (pN-N+), which classifies patients according to the number of positive lymph nodes and extranodal extension. METHODS: Consecutive, primary OSCC patients from seven previously published cohorts were included and classified according to the three pN-classifications: TNM7, TNM8 and pN-N+. Overall survival probabilities were summarised with the Kaplan-Meier method. We added each of the three metrics to a Cox regression adjusted for pT-category, lymph nodal yield, age, sex, radiotherapy and chemotherapy, and trained these models in one institution. We evaluated the predictive performance in the remaining six institutions and assessed the predicted 5-year risk of death using the area under the receiver operating characteristics curve (AUC) and Brier scores. RESULTS: All 1,905 included patients were classified according to TNM7 and pN-N+. A subset of 1,575 patients was additionally classified according to TNM8, leading to upstaging in 27.0%. The pN-N+ ranked overall best determined by the obtained AUC and Brier scores. In contrast to pN-N+, TNM7 and TNM8 both suffered from disproportionate patient distribution across pN-categories and poor pN-categorial discrimination on overall survival. CONCLUSIONS: The TNM8 pN-classification designates a larger subset to more advanced disease stages but failed to show improvement of its predictive performance compared to TNM7. The pN-categories of TNM7/8 are disproportionate and inconsistently discriminated. The pN-N+ conveyed the best measures of prognosis and should be considered in future TNM iterations.
BACKGROUND: We aimed to compare the predictive performance of pN-categories in oral squamous cell carcinoma (OSCC) encompassing the most recent 8th edition (TNM8), its predecessor (TNM7), and a newly proposed algorithm (pN-N+), which classifies patients according to the number of positive lymph nodes and extranodal extension. METHODS: Consecutive, primary OSCC patients from seven previously published cohorts were included and classified according to the three pN-classifications: TNM7, TNM8 and pN-N+. Overall survival probabilities were summarised with the Kaplan-Meier method. We added each of the three metrics to a Cox regression adjusted for pT-category, lymph nodal yield, age, sex, radiotherapy and chemotherapy, and trained these models in one institution. We evaluated the predictive performance in the remaining six institutions and assessed the predicted 5-year risk of death using the area under the receiver operating characteristics curve (AUC) and Brier scores. RESULTS: All 1,905 included patients were classified according to TNM7 and pN-N+. A subset of 1,575 patients was additionally classified according to TNM8, leading to upstaging in 27.0%. The pN-N+ ranked overall best determined by the obtained AUC and Brier scores. In contrast to pN-N+, TNM7 and TNM8 both suffered from disproportionate patient distribution across pN-categories and poor pN-categorial discrimination on overall survival. CONCLUSIONS: The TNM8 pN-classification designates a larger subset to more advanced disease stages but failed to show improvement of its predictive performance compared to TNM7. The pN-categories of TNM7/8 are disproportionate and inconsistently discriminated. The pN-N+ conveyed the best measures of prognosis and should be considered in future TNM iterations.
Authors: Lorenzo Bresciani; Lorenzo Giannini; Alberto Paderno; Fabiola Incandela; Walter Fontanella; Davide Mattavelli; Cesare Piazza Journal: Front Oral Health Date: 2021-09-23