Critical Issues in Head and Neck Oncology: Key Concepts from the Eighth THNO Meeting

Preface
Contents
1 The Bi-Directional Communication Between Tumour Cells and Other Components of the Tumour Microenvironment
	Introduction
	Biomarkers
	Autophagy
	Development of AMBRA-1 as a Prognostic Biomarker
	Sentinel Node Biopsy in Melanoma
	Cross-talk Mechanism in Melanoma
	Autophagy and Squamous Cell Carcinoma of the Head and Neck
		Oropharyngeal Squamous Carcinoma
		Cutaneous Squamous Cell Carcinoma
	Conclusion
	References
2 Immune Checkpoint Inhibition and Radiotherapy in Head and Neck Squamous Cell Carcinoma: Synergisms and Resistance Mechanisms
	Introduction
	Radiotherapy and Immunotherapy in HNSCC Treatment
	Immunological Effects of Radiotherapy
	Clinical Experiences with a Combination of Radiotherapy and Immune Checkpoint Inhibition in HNSCC
	Conclusions
	References
3 DNA Repair Mechanisms as a New Target in Head and Neck Cancer
	Introduction
	Immunostimulatory Effects Mediated by Radiotherapy
	Immunosuppressive Mechanisms Triggered by Radiotherapy
	Targeting DNA-Damage Response (DDR) Pathways
	ATM and ATR Inhibitors
	Immune Effects of ATR Inhibition
	Conclusions
	References
4 How to Standardize Molecular Profiling Programs for Routine Patient Care
	Introduction
	Relevant Aspects for Sample Collection and Processing
	Clinical Next-Generation Sequencing
	Targeted Gene Panel Sequencing
	Clinical Interpretation of Molecular Alterations
	Treatment and Follow-up
	Conclusions
	References
5 Novel Immune Oncology Targets Beyond PD-1/PD-L1 in Head and Neck Cancer
	Introduction
	Targeting Other Immune Checkpoints
	Combination of Anti-immune Checkpoint MoAbs with Other Type of Molecules
	Immunotherapeutic Vaccines for Human Papillomavirus (HPV)-Positive HNSCC
	Immunotherapy in the Early Stage Setting
	Conclusion
	References
6 Understanding Head and Neck Cancer Evolution to Guide Therapeutic Approaches
	Introduction
	Evolution of Treatment Naïve HNSCC
		Genomic Landscape of HNSCC
		Mutational and Copy Number Signatures
		Intra-tumoural Heterogeneity and Timing Evolutionary Events
	Evolution and Considerations for Therapy in HNSCC
		Developing Biomarkers and Therapies Informed by Evolution
		Recurrent and Metastatic HNSCC—Evolution on Treatment
		Circulating Tumour DNA
	Conclusions
	References
7 Sensitivity and Specificity of Extranodal Extension: Unlocking One of the Strongest Prognostic Factors in Head and Neck Cancer
	Introduction
	Pathological, Radiological, and Clinical Signs of ENE
	Sensitivity and Specificity of rENE for pENE
	Artificial Intelligence and Machine-Learning in Identifying rENE
	Biomarkers Associated with ENE
	Clinical Implication of ENE
	Conclusion
	References
8 Proton Therapy for Head and Neck Cancer
	Introduction
	Physical Properties of Proton Therapy
		Dosimetric Benefits of Proton Therapy
		Dosimetric Uncertainties of Proton Therapy for Head and Neck Patients
	Patient Selection for Proton Therapy
		Normal Tissue Complication Probability Models for Head and Neck Cancer
		Model-Based Approach
		Randomized Controlled Trials for Proton Therapy
	Outcomes After Proton Therapy of Head and Neck Cancers
		Skull-Base Chordomas and Chondrosarcomas
		Sinonasal Cancers
		Periorbital Tumours
		Salivary Gland Cancer
		Oropharyngeal Cancers
		Nasopharyngeal Cancers
	References
9 Treatment De-Escalation of HPV-Positive Oropharyngeal Cancer—Lessons Learnt from Recent Trials
	Introduction
	Why De-escalation?
	Results of Recent De-escalation Trials
	Lessons Learnt from De-escalation Studies
	Conclusions
	References
10 Treatment Intensification in Locoregionally Advanced Head and Neck Squamous Cell Carcinoma: What Are the Options and for Whom?
	Introduction
	Standard of Care Concurrent Chemoradiotherapy (CCRT)
		Toxicity of Standard of Care Concurrent Chemoradiotherapy
	Is Single Day Three-Weekly High-Dose Cisplatin Optimal to Enhance the Effect of Radiation?
	Concurrent Chemoradiotherapy in HPV-Positive Oropharyngeal Cancer Patients
	Treatment Intensification Beyond Concurrent Cisplatin- Based Chemoradiotherapy (summarized in Table 10.3)
		Combining Altered Fractionation Radiotherapy with Chemotherapy
		Adding More Cytotoxic Chemotherapy
		Adding Targeted Therapy
		Adding Approaches that Increase the Radio-Sensitivity of Hypoxic Cells
		Adding Immunotherapy (Immune Checkpoint Inhibitors)
	Conclusions
	References
11 Immune Checkpoint Inhibitors in the Curative Setting: Pre-clinical and Clinical Data
	Introduction
	Anti-PD-1/PD-L1 mAbs in Combination with Curative-Intent Primary Surgery
	Anti-PD-1/PD-L1 mAbs in Combination with Primary Curative-Intent (Chemo)Radiation
	Conclusion
	References
12 Carcinoma of Unknown Primary: Diagnostics and the Potential of Transoral Surgery
	Introduction
	History of Diagnostics in CUP
	Recent and Current Improvements
	Transoral Surgery—The Role of TLM and TORS
	Where Does TBM Come In?
	How to Perform TBM?
	How to Analyze the Resection Specimen?
	Extent of Resection
	The Case of True CUP
	Is TBM Really Indispensable?
	Definitive Treatment
	Conclusion
	References
13 Systemic Treatment Sequencing and Prediction of First-line Therapy Outcomes in Recurrent or Metastatic Head and Neck Cancer
	Introduction
	Defining the First Line
		First-Line Setting: Where it Begins and Ends
		First-Line Treatment: Pros and Cons
	Decision-Making Factors
		Categorical Variables
		Continuous Variables
	Treatment Sequencing
	Conclusions
	References
14 Patterns of Response to Immune Oncology Drugs: How Relevant Are They in SCCHN?
	Introduction
	Immunotherapy in Head and Neck Cancer
	Patterns of Response to Immune Checkpoint Inhibitors
		Pseudoprogression
		Hyperprogressive Disease (HPD)
	Conclusions
	References
15 Stereotactic Body Radiation Therapy in the Management of Recurrent and/or Oligometastatic Head and Neck Cancer
	Introduction
	Reirradiation Using SBRT in Recurrent or Second Primary Head and Neck Cancer
	SBRT in HNC Patients with Oligometastatic Disease
	Conclusion and Recommendations
	References
16 Precision Medicine in the Treatment of Malignancies Involving the Ventral Skull Base: Present and Future
	Introduction
	Sinonasal Tumors
		Intestinal-Type Adenocarcinoma
		Squamous Cell Carcinoma
		Olfactory Neuroblastoma
		Mucosal Melanoma
		Sinonasal Undifferentiated Carcinoma and SWI-SNF-Deficient Sinonasal Carcinomas
		Sinonasal Neuroendocrine Carcinomas
		Adenoid Cystic Carcinoma
	Nasopharyngeal Tumors
	Non-epithelial Skull Base Cancers
		Chondrosarcoma
		Chordoma
	Conclusions
	References
17 Modern Day Reconstruction of the Facial Bones
	Introduction
	Essential Steps
	Indications
	Resection
	Mandibular Reconstruction
	Maxillary Reconstruction
	Limitations and Future Developments
	Conclusion
	References
18 Targeting Molecular Residual Disease Using Novel Technologies and Clinical Trials Design in Head and Neck Squamous Cell Cancer
	Introduction
	Liquid Biopsy and Molecular Residual Disease
	Assays for MRD Detection
	Evaluation of MRD in HNSCC
		HPV DNA
		Mutation-Based ctDNA
		Methylated cfDNA
	MRD Clinical Trials Design
	Conclusions
	References
19 New Developments in Surgery for Malignant Salivary Gland Tumors
	Introduction
	Developments in Ablative Surgery
		Transoral Surgery: TLM and TORS
		Transnasal Endoscopic Surgery
	Developments in Reconstructive Surgery
		Developments in Midface Reanimation
		Developments in Single Stage Reconstruction of Complex Defects Using Free Flaps
	Conclusion
	References
20 New Systemic Therapies in Salivary Gland Cancer
	Introduction
	Subtypes of Salivary Gland Cancers
		Adenoid Cystic Carcinoma
		Mucoepidermoid Carcinoma
		Salivary Duct Carcinoma
		Mammary Analogue Secretory Carcinoma
		Acinic Cell Carcinoma
		Polymorphous Adenocarcinoma
		Adenocarcinoma not Otherwise Specified (NOS)
		Carcinoma ex Pleomorphic Adenoma
		Other Subtypes
	Immunotherapy
	Conclusions
	References
21 Exercise and Nutrition Interventions in Head and Neck Cancer
	Introduction
	Malnutrition and Nutritional Interventions
		Immunonutrition
	Physical Activity and Quality of Life
	Prophylactic Measures
	Conclusion and Recommendations
	References
22 Digital Technologies in Supportive Head and Neck Cancer Care: A Promise?
	Introduction
	Supportive Care and Self-management
	Digital Supportive Care
	The Case of Oncokompas
	Conclusion
	References