Mohammed Kashani-Sabet1, James R Miller1, Serigne Lo2,3, Mehdi Nosrati1, Jonathan R Stretch2,3,4, Kerwin F Shannon2,3,4, Andrew J Spillane2, Robyn P M Saw2,3,4, James E Cleaver5, Kevin B Kim1, Stanley P Leong1, John F Thompson2,3,4, Richard A Scolyer2,3,4,6. 1. Center for Melanoma Research and Treatment, California Pacific Medical Center and Research Institute, San Francisco, California. 2. Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia. 3. Central Clinical School, The University of Sydney, Sydney, New South Wales, Australia. 4. Royal Prince Alfred Hospital, Sydney, New South Wales, Australia. 5. Department of Dermatology, University of California at San Francisco, San Francisco, California. 6. New South Wales Health Pathology, Sydney, New South Wales, Australia.
Abstract
BACKGROUND: Mitotic rate is a strong, independent prognostic factor in patients with melanoma. However, incorporating it into the melanoma staging system has proved challenging. METHODS: The prognostic impact of mitotic rate was assessed in a melanoma cohort comprising 5050 patients from 2 geographically distinct populations. Computer-generated cut points for mitotic rate were constructed to determine its impact on melanoma-associated survival using Kaplan-Meier and multivariate regression analyses. The impact of mitotic rate also was assessed in randomly split training and validation sets. RESULTS: Mitotic rate had a nonlinear impact on survival, as evidenced by unequally spaced cut points. An index incorporating these cut points that was constructed from one population produced significantly more accurate predictions of survival in the other population than using the entire scale of mitotic rate. An index constructed from the combined cohort was found to be independently predictive of survival, with an impact comparable to that of ulceration. Optimal high-versus-low cut points for mitotic rate were generated separately for each T category (<2 mitoses/mm2 vs ≥2 mitoses/mm2 for T1 melanoma, <4 mitoses/mm2 vs ≥4 mitoses/mm2 for T2 melanoma, <6 mitoses/mm2 vs ≥6/mitoses/mm2 for T3 melanoma, and <7 mitoses/mm2 vs ≥7 mitoses/mm2 for T4 melanoma). Using Kaplan-Meier analysis, elevated mitotic rate was found to have an impact on survival comparable to that of ulceration within each T category. Application of the index for mitotic rate that was constructed from the training data set demonstrated an independent impact in the validation data set, with a significance similar to that of ulceration. CONCLUSIONS: The results of the current study demonstrated the comparable prognostic impact of mitotic rate and ulceration, providing support for its reincorporation into the T category.
BACKGROUND: Mitotic rate is a strong, independent prognostic factor in patients with melanoma. However, incorporating it into the melanoma staging system has proved challenging. METHODS: The prognostic impact of mitotic rate was assessed in a melanoma cohort comprising 5050 patients from 2 geographically distinct populations. Computer-generated cut points for mitotic rate were constructed to determine its impact on melanoma-associated survival using Kaplan-Meier and multivariate regression analyses. The impact of mitotic rate also was assessed in randomly split training and validation sets. RESULTS: Mitotic rate had a nonlinear impact on survival, as evidenced by unequally spaced cut points. An index incorporating these cut points that was constructed from one population produced significantly more accurate predictions of survival in the other population than using the entire scale of mitotic rate. An index constructed from the combined cohort was found to be independently predictive of survival, with an impact comparable to that of ulceration. Optimal high-versus-low cut points for mitotic rate were generated separately for each T category (<2 mitoses/mm2 vs ≥2 mitoses/mm2 for T1 melanoma, <4 mitoses/mm2 vs ≥4 mitoses/mm2 for T2 melanoma, <6 mitoses/mm2 vs ≥6/mitoses/mm2 for T3 melanoma, and <7 mitoses/mm2 vs ≥7 mitoses/mm2 for T4 melanoma). Using Kaplan-Meier analysis, elevated mitotic rate was found to have an impact on survival comparable to that of ulceration within each T category. Application of the index for mitotic rate that was constructed from the training data set demonstrated an independent impact in the validation data set, with a significance similar to that of ulceration. CONCLUSIONS: The results of the current study demonstrated the comparable prognostic impact of mitotic rate and ulceration, providing support for its reincorporation into the T category.
Authors: Danielle R Davari; Irene Orlow; Peter A Kanetsky; Li Luo; Klaus J Busam; Ajay Sharma; Anne Kricker; Anne E Cust; Hoda Anton-Culver; Stephen B Gruber; Richard P Gallagher; Roberto Zanetti; Stefano Rosso; Lidia Sacchetto; Terence Dwyer; David C Gibbs; David W Ollila; Colin B Begg; Marianne Berwick; Nancy E Thomas Journal: Curr Oncol Date: 2021-11-16 Impact factor: 3.677
Authors: Alessandra Buja; Andrea Bardin; Giovanni Damiani; Manuel Zorzi; Chiara De Toni; Riccardo Fusinato; Romina Spina; Antonella Vecchiato; Paolo Del Fiore; Simone Mocellin; Vincenzo Baldo; Massimo Rugge; Carlo Riccardo Rossi Journal: Front Oncol Date: 2021-11-16 Impact factor: 6.244