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      Standardized Diagnostics Including PET-CT Imaging, Bilateral Tonsillectomy and Neck Dissection Followed by Risk-Adapted Post-Operative Treatment Favoring Radio-Chemotherapy Improve Survival of Neck Squamous Cell Carcinoma of Unknown Primary Patients

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          Abstract

          Background

          About five to 10% of cancers in the head and neck region are neck squamous cell carcinoma of unknown primary (NSCCUP). Their diagnosis and treatment are challenging given the risk of missing occult tumors and potential relapse. Recently, we described human papillomavirus (HPV)-related NSCCUP-patients (NSCCUP-P) as a subgroup with superior survival. However, standardized diagnostic workup, novel diagnostic procedures, decision-making in the multidisciplinary tumor board (MDTB) and multimodal therapy including surgery and post-operative radio-chemotherapy (PORCT) may also improve survival.

          Methods

          For assessing the impact of standardized diagnostic processes simultaneously established with the MDTB on outcome, we split our sample of 115 NSCCUP-P into two cohorts treated with curative intent from 1988 to 2006 (cohort 1; n = 53) and 2007 to 2018 (cohort 2; n = 62). We compared diagnostic processes and utilized treatment modalities applying Chi-square tests, and outcome by Kaplan–Meier plots and Cox regression.

          Results

          In cohort 2, the standardized processes (regular use of [ 18F]-FDG-PET-CT imaging followed by examination under anesthesia, EUA, bilateral tonsillectomy and neck dissection, ND, at least of the affected site) improved detection of primaries ( P = 0.026) mostly located in the oropharynx ( P = 0.001). From 66.0 to 87.1% increased ND frequency ( P = 0.007) increased the detection of extracapsular extension of neck nodes (ECE+) forcing risk factor-adapted treatment by increased utilization of cisplatin-based PORCT that improved 5-years progression-free and overall survival from 60.4 and 45.3 to 67.7% ( P = 0.411) and 66.1% ( P = 0.025).

          Conclusions

          Standardized diagnostic workup followed by ND and risk-factor adapted therapy improves survival of NSCCUP-P.

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          Most cited references35

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          Regression Models and Life-Tables

          D R Cox (1972)
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            The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging.

            The American Joint Committee on Cancer (AJCC) staging manual has become the benchmark for classifying patients with cancer, defining prognosis, and determining the best treatment approaches. Many view the primary role of the tumor, lymph node, metastasis (TNM) system as that of a standardized classification system for evaluating cancer at a population level in terms of the extent of disease, both at initial presentation and after surgical treatment, and the overall impact of improvements in cancer treatment. The rapid evolution of knowledge in cancer biology and the discovery and validation of biologic factors that predict cancer outcome and response to treatment with better accuracy have led some cancer experts to question the utility of a TNM-based approach in clinical care at an individualized patient level. In the Eighth Edition of the AJCC Cancer Staging Manual, the goal of including relevant, nonanatomic (including molecular) factors has been foremost, although changes are made only when there is strong evidence for inclusion. The editorial board viewed this iteration as a proactive effort to continue to build the important bridge from a "population-based" to a more "personalized" approach to patient classification, one that forms the conceptual framework and foundation of cancer staging in the era of precision molecular oncology. The AJCC promulgates best staging practices through each new edition in an effort to provide cancer care providers with a powerful, knowledge-based resource for the battle against cancer. In this commentary, the authors highlight the overall organizational and structural changes as well as "what's new" in the Eighth Edition. It is hoped that this information will provide the reader with a better understanding of the rationale behind the aggregate proposed changes and the exciting developments in the upcoming edition. CA Cancer J Clin 2017;67:93-99. © 2017 American Cancer Society.
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              Nonparametric Estimation from Incomplete Observations

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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                07 May 2021
                2021
                : 11
                : 682088
                Affiliations
                [1] 1 Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Leipzig , Leipzig, Germany
                [2] 2 Department of Radiation Oncology, University Hospital Leipzig , Leipzig, Germany
                [3] 3 Department of Nuclear Medicine, University Hospital Leipzig , Leipzig, Germany
                [4] 4 Department of Pathology, University Hospital Leipzig , Leipzig, Germany
                [5] 5 Department of Internal Medicine II, Division of Oncology, University Cancer Center Leipzig (UCCL), Leipzig University Medicine , Leipzig, Germany
                Author notes

                Edited by: Panagiotis Balermpas, University Hospital Zürich, Switzerland

                Reviewed by: Jens Von Der Gruen, University Hospital Frankfurt, Germany; Alexander Rühle, Freiburg University Medical Center, Germany

                *Correspondence: Gunnar Wichmann, Gunnar.Wichmann@ 123456medizin.uni-leipzig.de

                †These authors have contributed equally to this work and share first authorship

                ‡These authors have contributed equally to this work and share senior authorship

                This article was submitted to Head and Neck Cancer, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2021.682088
                8138574
                34026656
                a950553f-0b07-4b4e-a0ed-e664c8433e2d
                Copyright © 2021 Wichmann, Willner, Kuhnt, Kluge, Gradistanac, Wald, Fest, Lordick, Dietz, Wiegand and Zebralla

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 17 March 2021
                : 07 April 2021
                Page count
                Figures: 5, Tables: 3, Equations: 0, References: 36, Pages: 14, Words: 6111
                Categories
                Oncology
                Original Research

                Oncology & Radiotherapy
                cancer of unknown primary (cup),neck dissection (nd),extracapsular extension of neck nodes (ece),cisplatin-based postoperative radio-chemotherapy,outcome research,head and neck cancer (hnc),head and neck squamous cell carcinoma (hnscc)

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